Bioengineering Alumnae Establish Undergraduate Scholarship

Bioengineering, Office of Development & Alumni Affairs

PITTSBURGH (Sept. 16, 2020) … Two bioengineering alumnae from the University of Pittsburgh established a scholarship for students, who like them, are passionate about STEM education. The Stephanie F. Coquia and Angela L. Fu Scholarship in Bioengineering will provide support for tuition and other education-related expenses for a sophomore, junior, or senior student in good academic standing in the Department of Bioengineering at the Swanson School of Engineering. Preference will be given to students who reside in states outside of Pennsylvania and who have demonstrated involvement in extracurricular activities in high school. Drs. Coquia (BS BioE ‘02) and Fu (BS BioE ‘03), who became friends during their time at Pitt, want to acknowledge the program’s impact on their professional lives and provide support for current students to experience the same opportunity. “I wouldn’t be where I am today without the University of Pittsburgh and the Department of Bioengineering, and I wouldn’t have gone to Pitt or gotten a bioengineering degree if I hadn’t received a scholarship,” said Dr. Coquia. “So, this is my way of giving back. I am happy to be sponsoring this scholarship with Angela.” “The one thing that I have enjoyed most after graduating and starting my career is mentoring current students in their post graduation and career choices,” said Dr. Fu. “The scholarship will hopefully assist one student financially so they can focus on the decisions affecting their future.” The pair studied in the department during its nascent years and flourished along with the program. Since its first graduating class in 2000, the number of degrees awarded has tripled from roughly 20 in 2000 to 66 this past spring semester. “I am thankful to Stephanie and Angela for their generosity. It is wonderful to see our former students thrive in their professional careers and want to give back to the department,” said Sanjeev Shroff, distinguished professor and Gerald E. McGinnis Chair of bioengineering. “I am delighted that this scholarship will help provide a Swanson School education to deserving students and contribute to the growing number of successful bioengineering alumni.” # # #

How to Handle a Zombie Outbreak

Covid-19, Bioengineering, Investing Now

In the middle of the Atlantic lies Grimmsport, a fictional island that has identified an outbreak of Zom-B13 which turns the island residents into mindless zombies. This thinly veiled theme for the 2020 Summer with Swanson camp helped teach high school students about the scientific aspects of a pandemic. The University of Pittsburgh’s CampBioE and Mascaro Center for Sustainable Innovation joined efforts to create a virtual camp that served underrepresented pre-college students in the Swanson School of Engineering’s Investing Now program. The students’ mission was to contain and treat the zombie outbreak, and the first step was to mitigate the spread. “We discussed the importance of a mask and its ability to help filter cleaner air for individuals to breathe,” said Ankith Rao (BioE ‘21). “They learned about human factors in product development and how to create a mask for a universal user. The students then sketched designs and physically prototyped masks with objects from around the house.” With a protective measure in hand, the students then learned how to research reliable information on the outbreak. The camp counselors demonstrated the CRAP test to help students consider four critical areas in identifying a trustworthy source: currency, reliability, authority and purpose. They used these new skills to complete an online scavenger hunt to learn more about vaccines. As part of the overall theme, the students also had to use engineering concepts to solve a series of puzzles that would aid in eliminating the virus. “In one of our modules, the students intercepted an email from zombie island, but they first had to learn how to use ASCII code to translate a clue that was coded in binary notation,” said Lucy Kress (BioE ‘21). One of the other clues included a circuit with a hidden DNA sequence to decode. “Students used software to figure out the protein sequence of the DNA, which was subsequently used to create a 3D model of the protein that served as the antigen for the vaccine,” said Pooja Chawla (BioE ‘22). “They then participated in a detailed virtual lab that demonstrated how vaccines are made.” After gaining a better understanding of how vaccines are developed, the students put their efforts toward creating a way to figure out who is infected. Polymerase chain reaction (PCR) technology can rapidly detect viral DNA using primers – short, single-stranded DNA sequences that are specific to the disease. “Any time there is a new virus, you have to be able to identify if a person has been infected,” said Patricia Donehue, a Pitt biological sciences alumna. “We designed primers and introduced the students to PCR and gel electrophoresis as one means of identifying infection. They applied this technique to the clues to discover who may have been exposed to the disease.” The group also used artificial intelligence to set up a classifier that could identify if a face was human or zombie. In this exercise, they demonstrated bias in AI and discussed its implications in modern technology. Finally, the students learned about the pathology of the virus through a series of escape rooms that represented different stages of infection. “Each room had a patient chart with symptoms, and they used a website with a human anatomy model to solve the clues and figure out who was infected,” said Garima Patel (BioE ‘22). In the end, the students successfully created a vaccine, treated the population, and eradicated the zombie outbreak at Grimmsport. While the overall feedback for Summer with Swanson was positive, the counselors encountered a variety of obstacles along the way. Many of the issues involved access to technology and an internet connection. “Some students only had access to phones and tablets while others were limited by website restrictions on their school’s technology,” said Donehue. “Adaptability was an important aspect of this year’s camp. We had to make sure that the students were able to participate in each of the activities, regardless of what technology was available.” The Department of Bioengineering’s CampBioE, like many other programs, had to reframe their curriculum to adapt to coronavirus restrictions. The changes were challenging in many ways, but the solutions also opened new doors. “While the need to do everything virtually created some significant barriers, it also broke down some barriers,” said Steven Abramowitch, associate professor of bioengineering at Pitt and director of CampBioE. “Physical distance was no longer a factor, which allowed us to extend our programming out-of-state and reach audiences that would not have been able to participate otherwise.” The group plans to eventually package their activities on their website so that middle and high school educators across the nation can continue to “inspire tomorrow’s engineers.” # # #

Bioengineering Student Plugs in to Complex Tech

Bioengineering, Student Profiles

Reposted from Pittwire. Click here to see the original story. When Audrey Case was 19 years old, she suffered her third concussion while playing intramural soccer. She was carried off the field and rushed to the hospital. “I just kept quietly repeating, ‘Not again, I can’t do this again,’” said Case, now a third-year, bioengineering student at the University of Pittsburgh’s Swanson School of Engineering. “But that one little injury changed the course of my college career.” Case recalled the incident, as well as her prior two concussions in her first published book, “Plugged In: The Past, Present, and Future of Brain Computer Interfaces,” which breaks down research in a lay-friendly way. The book was released on Amazon Kindle in late July. Although she recovered from each concussion, the most recent injury changed Case's course of study by interesting her in the human brain and the science behind its recovery from injuries. It may not be as iconic as Isaac Newton’s mythical “a-ha” moment with the apple tree, but her recovery did bring her to Pitt’s Rehab Neural Engineering Labs in 2018. There, she learned more about new rehabilitation technologies aimed toward helping people regain lost mobility and function, including brain-computer interface (BCI) research. “I started to think, ‘What if I hadn’t recovered?’ or ‘What if it was a more permanent injury?’” she said. Case’s current work uses magnetic resonance imaging, or MRI, to map out brain activity related to movements and sensations of individual fingers in people with spinal cord injury. She said she eventually hopes to work in biotechnology research after completing her studies. Jennifer Collinger, assistant professor and research operations director of the labs, said she was surprised when Case told her she was writing a book on the topic with only months of experience. However, it was clear to her that Case was “a quick learner” and was genuinely excited and curious about the work. “She did a great job with being able to communicate this information to a general audience,” Collinger said. “I was impressed to see the number of references provided in each chapter and how she hit on a lot of the major topics in this field right now.” One topic she covers is testing performed with Nathan Copeland, a man with paralysis who collaborated on Pitt research. In a 2016 first in humans, he demonstrated a technology that allowed him to experience the sensation of touch through a robotic arm that he controlled with his brain. This led to him presenting at a science conference in Japan and meeting President Barack Obama. “He started spinning the robotic arm with its extra joints, and the principal investigators had to tell him to stop,” Case said. “He said, ‘But it’s like I have two wrists and it’s so cool.’ I met him during a break in testing, but he was funny, bright and interesting.” For her book, Case drew on previous experiences speaking with friends and family about brain-computer interface technology, as well as reading what was available about it. She said she hopes the general public will have a better understanding of BCI research and the progress being made for people with limited mobility. “It was really difficult to speak with people, because they weren’t understanding what I was saying,” she said. “The language I was reading about this research was so vague and there was so much technical jargon. I also read about how people were so afraid of driverless cars, because they didn’t know how they worked. I was worried something similar would happen with BCI technology.” Fang Liu, a research engineer in the labs, and Case’s primary mentor, agreed. “It’s great to give people some knowledge about this,” Liu said. “We work with spinal cord injury patients and stroke patients, and it’s hard for them to adjust to everyday life. We try to make people realize what we can do in the labs to help them.”

Improving Ladder Safety, One Rung at a Time

Bioengineering

PITTSBURGH (August 11, 2020) … When using a ladder, whether you are a professional roofer or an everyday homeowner, safety should always be the first step. There is an estimated $24 billion annual cost of ladder injuries in the U.S., where falls account for 26 percent of nonfatal and 16 percent of fatal workplace injuries. When the fall is not fatal, it often leads to serious injury, and workers who experience a ladder-related fall have a median time of 20 days away from work. Losing one’s footing is a common accident and can lead to serious injury; yet, research on falls from ladders is lacking. The University of Pittsburgh’s Kurt Beschorner will use a $1,840,869 grant from the National Institute for Occupational Safety and Health (NIOSH) to develop safer ladder designs and individual risk factors of ladder falls. The work will focus on measuring friction as the pathway for the ladder and individual to influence slip and fall risk. “A slip happens when there is insufficient friction between the shoe surface and ladder rung, but little is known about how ladder design or an individual’s body affects slip and fall risk,” said Beschorner, associate professor of bioengineering at Pitt’s Swanson School of Engineering. Previous award-winning work from students Erika Pliner and Ellen Martin in the Human Movement & Balance Laboratory provided foundational understanding on ladder fall risk factors. Some groups at increased risk are older adults, inexperienced climbers, and people with lower body strength. The researchers will build on these preliminary findings with this larger study. The lab will use two measurements to determine the impact of ladder design and individual factors on slip and fall risk: required friction and available friction. “The available friction is the amount that occurs between a shoe and rung,” Beschorner explained. “When that value is less than the amount of friction that is required to complete a task, there is a risk of a slip-and-fall event.” To measure the required friction, the research group will install force plate technology onto rungs and build a ladder around it. They will combine force data with motion data to better understand how various factors affect slips and falls. For the available friction, they will use a device that simulates a slip under controlled conditions and measure how much friction is generated. They will create a slippery rung scenario with a harnessed participant to test whether an individual slips under these specific conditions. “While falls are dangerous occupationally, ladders are also a consumer product, and accidents at home contribute to the annual number of injuries and fatalities,” said Beschorner. “This award gives us an opportunity to develop a mechanistic model to see how these individual factors influence fall risk,” he continued. “We will study these measurements of friction and how they relate to slipping in order to establish safety guidelines, which will hopefully lead to a significant reduction in severe injuries and fatalities in both the workplace and at home.” This study will extend the lab’s prior work on friction between shoes and walking surfaces to ladder slipping. # # #

Infant Heart-Assist Pump Secures $4.7M from the DOD

Bioengineering

PITTSBURGH (July 23, 2020) … The Center for Disease Control estimates that roughly 40,000 infants are born with congenital heart defects (CHDs) each year. Among that population, 25 percent are critical cases that require cardiac surgery. The waitlist for a heart transplant continues to grow; yet, the only FDA-approved life-saving device for CHD has shortcomings and is based on technology from the 1970s. A multi-institutional team, including faculty and students from the Swanson School of Engineering (SSoE) and McGowan Institute for Regenerative Medicine (MIRM), recently received funding to advance this technology. The PediaFlow® Ventricular Assist Device (VAD), a heart-assist pump for infants and young children, received a $4.7 million grant from the U.S. Department of Defense (DoD). The device, originally developed at the University of Pittsburgh, is intended to support patients with congenital and/or acquired heart disease. James Antaki, the Susan K. McAdam Professor of Heart Assist Technology at Cornell University’s Meinig School of Biomedical Engineering, will lead the project’s development and preclinical validation. (See Cornell University’s announcement) “It is a new lease on life for this device for children who have no other alternative,” said Antaki. The device is a miniaturized, magnetically levitated, rotary VAD that is roughly the size of a AA battery and can provide sufficient blood flow for infants and small children. Implantation of the device could also potentially rehabilitate a child’s heart back to health, thus obviating the need for a cardiac transplant. The project began in 2002 at Pitt and builds upon blood pump technology developed by several SSoE and MIRM faculty and students over the past decade. After evaluating three pump topologies, the research group chose a mixed-flow configuration and applied a computational fluid dynamics approach to optimize the design from the point of view of outstanding biocompatibility. Bench and preclinical studies have demonstrated outstanding biocompatibility of the PediaFlow VAD. “Despite the clinician mantra that ‘babies are not just tiny adults,’ pediatric heart pump development has been historically limited to the miniaturization of existing adult devices with minimal success,” said Salim Olia (BioE PhD ’18), adjunct assistant professor of surgery at the University of Pennsylvania School of Medicine. Olia conducted the crucial bench and preclinical PediaFlow tests as part of his PhD dissertation in the Department of Bioengineering at Pitt and is continuing his work for the DoD award. “PediaFlow represents a clean slate approach of designing from the ground up with the primary objective of maximizing patient safety by minimizing blood damage,” he continued. Pitt’s subcontract on this DoD award is a collaboration between SSoE and MIRM. In particular, Marina Kameneva, research professor of surgery and bioengineering, and William Wagner, director of the McGowan Institute and distinguished professor of surgery, bioengineering and chemical engineering, will direct studies assessing the biocompatibility and overall suitability of the PediaFlow pumps developed under the DoD award for clinical use. According to Harvey Borovetz, Distinguished Professor of Bioengineering and the Robert L. Hardesty Professor of Surgery, “It is our goal at the end of the three-year DoD award to have completed development of the PediaFlow heart-assist pump, in anticipation of submitting an Investigational Device Exemption (IDE) application to the FDA and initiating clinical feasibility studies in these very special patients.” # # #

Pitt’s Center for Medical Innovation awards three novel biomedical projects with $60,000 in Round 1 2020 Pilot Funding

Bioengineering

PITTSBURGH (July 1, 2020) … The University of Pittsburgh’s Center for Medical Innovation (CMI) awarded grants totaling $60,000 to three research groups through its 2020 Round-1 Pilot Funding Program for Early Stage Medical Technology Research and Development. The latest funding proposals include a virus-resistant wear-resistant textile, a system for removal of cell-free plasma hemoglobin in extracorporeal therapies, and a biocontainment unit for reducing viral transmission to healthcare workers and patients CMI, a University Center housed in Pitt’s Swanson School of Engineering (SSOE), supports applied technology projects in the early stages of development with “kickstart” funding toward the goal of transitioning the research to clinical adoption. Proposals are evaluated on the basis of scientific merit, technical and clinical relevance, potential health care impact and significance, experience of the investigators, and potential in obtaining further financial investment to translate the particular solution to healthcare. “This is our eighth year of pilot funding, and our leadership team could not be more excited with the breadth and depth of this round’s awardees,” said Alan D. Hirschman, PhD, CMI Executive Director. “This early-stage interdisciplinary research helps to develop highly specific biomedical technologies through a proven strategy of linking UPMC’s clinicians and surgeons with the Swanson School’s engineering faculty.” AWARD 1: “Wash-Stable and Mechanically Durable Anti-Virofouling Medical Textiles”For the development of a nanoparticle-based reusable textile for use in healthcare settings. Paul W. Leu, PhD;  Associate Professor of Industrial Engineering, Swanson School of EngineeringRobert Shanks , PhD  Associate Professor of Ophthalmology, UPMC                                                 Eric Romanowski, MS,  Research Director, Charles T. Campbell Laboratory of Ophthalmic Microbiolog AWARD 2: “Targeted removal of cell-free plasma hemoglobin in extracorporeal therapies” For an extracorporeal hemoperfusion device that removes plasma hemoglobin from a blood column using treated porous beads. Nahmah Kim-Campbell, MD, MS, Assistant Professor of Critical Care Medicine and PediatricsWilliam Federspiel, PhD; Professor of Bioengineering, Swanson School of EngineeringRyan Orizondo, PhD  Researcher in Bioenengineering, Swanson School of Engineerin AWARD 3: “Individual Biocontainment Unit for Reducing Viral Transmission to healthcare Workers and Patients”For the expedited development, approval and manufacture of a novel device for use with ICU patients to reduce contamination by aerosolized particles. David M. Turer, MD, MS Department of Plastic Surgery, UPMCHeng Ban, PhD; Professor Mechanical Engineering and Material Science, Swanson School of EngineeringJ.Peter Rubin, MD;  Chairman, Dept of Plastic Surgery, UPMC # # # About the University of Pittsburgh Center for Medical Innovation The Center for Medical Innovation is a collaboration among the Swanson School of Engineering, the Clinical and Translational Science Institute (CTSI), the Innovation Institute, and the Coulter Translational Research Partnership II (CTRP). CMI was established in 2012 to promote the application and development of innovative biomedical technologies to clinical problems; to educate the next generation of innovators in cooperation with the schools of Engineering, Health Sciences, Business, and Law; and to facilitate the translation of innovative biomedical technologies into marketable products and services. Over 70 early-stage projects have been supported by CMI with a total investment of over $1.4 million since inception.

Reversing Drug Resistance in Breast Cancer

Bioengineering

PITTSBURGH (June 29, 2020) … Roughly one in eight women in the United States will develop invasive breast cancer over the course of  her lifetime, and HER2-positive (HER2+) breast cancers represent about 25 percent of all breast cancer cases. Though multiple therapies exist, most patients will develop metastatic disease and resistance to current treatments. A collaborative research group from the University of Pittsburgh and Harvard Medical School studied the mechanisms behind tumor cell resistance to therapies targeting metastatic HER2+ breast cancer and recently published their work in Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.2000648117). The group examined the tumor microenvironment -- a collection of cells, molecules, and blood vessels that surround and influence tumor cells -- to get the full picture of what drives this resistance. They found that fibroblasts, a cell type important to tissue regeneration, play a large role. “Our study shows that fibroblasts promote drug resistance through a parallel signaling pathway in a subset of HER2+ breast cancer cells,” said Ioannis Zervantonakis, assistant professor of bioengineering at Pitt’s Swanson School of Engineering and member of the Cancer Biology Program at the University of Pittsburgh Hillman Cancer Center. Cancer cells grow uncontrollably, which is partially driven by continuous activation of proteins called kinases. HER2+ breast tumors have high levels of the HER2 receptor kinase that is important for their growth and is a major drug target. Anti-cancer drugs -- like lapatinib -- work to interfere with kinases, but because of this parallel signaling, fibroblasts are able to protect tumor cells and counteract the drug’s inhibitory effects. Compare this cell-to-cell signaling process to communication through a radio. The radio antenna is analogous to a receptor in the cell that is activated when an electrical signal is received. Radios can have multiple antennas to respond to different electrical signals. “By analogy, cancer cells have multiple receptors (antennas) that can be activated by signals in their environment,” explained Zervantonakis. “In the radio example, transmission of an electrical signal produces a sound. While in cancer cells, fibroblast-derived signals stimulate cancer growth.” You can produce a series of sounds, and even amplify the volume, by receiving more than one signal at a time through activation of parallel pathways. “In this scenario, the HER2+ kinase is one signal that is continuously activating sound, and then there is another pathway through which signals emitted by fibroblasts activate sound,” he continued. “Lapatinib only blocks the HER2+ kinase signal, but through another pathway, the fibroblasts are able to transmit signals to keep the cancer cells alive or allow them to grow.” The findings in this paper are important for restoring sensitivity to breast cancer therapies and developing treatments that are more effective. “Sensitivity to these drugs can be re-established through a combination of therapies that inhibit critical proteins in the pathway activated by fibroblasts,” said Zervantonakis. “Particularly, combination therapies with the FDA-approved drug everolimus and investigational agents targeting anti-apoptotic proteins were effective in restoring drug sensitivity in fibroblast-protected cancer cells.” The next step for Zervantonakis and his lab is to create predictive mathematical models to identify the fibroblast density range in tumors that will elicit drug resistance. From there, they can develop personalized therapies to improve outcomes in HER2+ breast cancer. This research was supported by a K99/R00 grant (R00CA222554) from the National Cancer Institute of the National Institutes of Health along with support from the Hillman Cancer Center, Swanson School of Engineering and Department of Bioengineering. # # #

A Micro Look at Metastatic Environments in Ovarian Cancer

Bioengineering

PITTSBURGH (June 16, 2020) … According to the American Cancer Society, a woman's risk of being diagnosed with ovarian cancer during her lifetime is about one in 78. The majority of ovarian cancer patients are diagnosed with metastatic disease that spreads to other parts of the body and have a low five-year survival rate. Ioannis Zervantonakis, assistant professor of bioengineering at the University of Pittsburgh, received an award from the Elsa U. Pardee Foundation to develop microfluidic models of metastatic microenvironments in ovarian cancer and study mechanisms of cancer cell survival in these microenvironments. The tumor microenvironment is the collection of cells, molecules, and blood vessels that surround tumor cells. Tumor growth, metastasis, and response to therapy is governed by a complex interaction network between tumor cells and those components. “We hypothesize that during the early steps of metastasis formation, ovarian cancer cells recruit macrophages that in turn disrupt mesothelial barrier function to support adhesion and invasion,” said Zervantonakis, who runs the Tumor Microenvironment Engineering Laboratory in the Swanson School of Engineering. In this project, they will use microfluidic technology, which allows researchers to create precise and controlled environments that can mimic human systems. Zervantonakis will develop a novel microfluidic device that will recreate a dynamic tumor-macrophage-mesothelial 3D metastatic microenvironment. The research team will profile these metastatic microenvironments in vivo and evaluate the predictive capacity of the microfluidic device. They will also analyze ovarian cancer signaling in hopes of identifying targets that can be combined with current therapies to more effectively eliminate disease. “Understanding cell behavior in native tumor microenvironments and developing new strategies to deliver therapeutics directly to tumor cells are critical in improving and extending patients’ lives,” said Zervantonakis. # # #

BioE Graduate Student Awarded 2020 GPSG Leadership and Service Award

Bioengineering, Student Profiles

PITTSBURGH (June 1, 2020) — The University of Pittsburgh Graduate and Professional Student Government (GPSG) presented Haley Fuller, vice president of the Swanson School of Engineering’s Engineering Graduate Student Organization (EGSO), with the 2020 GPSG Leadership and Service Award. Fuller is a second-year graduate student in bioengineering. The Award recognizes current Pitt graduate and professional students’ service or leadership to the University, surrounding community, and world at large. Fuller joined EGSO when she matriculated in 2018 and, within the first two months, fulfilled the Communications Officer position, which is normally held by more senior students. Driven to be more involved, she ran for and was elected Vice President of EGSO within her second year as a graduate student. She also joined the Pitt chapter of the Biomedical Engineering Society (BMES), where she was selected as first-year representative for her class. “When I moved to Pittsburgh from the Washington, DC, area, I was eager to make friends and get involved with my new graduate program right off the bat. EGSO accomplished exactly this for me, as well as has provided academic and professional support over the past two years of my involvement,” said Fuller. “Since EGSO is an interdepartmental organization run entirely by student volunteers, I was immediately greeted at the door by the most enthusiastic, self-driven individuals across various engineering disciplines who have since become both my friends and scientific collaborators.” In addition to her work in EGSO and BMES, Fuller serves as a program facilitator for Investing Now, an initiative that introduces Pittsburgh high school students to STEM disciplines. The role requires training throughout the spring semester in preparation for teaching self-directed two-hour sessions, four days a week, through the month of July, all while continuing her own research in Warren Ruder’s Synthetic Biology and Biomimetics Laboratory at Pitt. “Working alongside like-minded students has driven me to become involved in other organizations across campus, as well as encouraged me to pursue projects on campus in which I’ve gotten the chance to interact directly with faculty members to influence institutional direction for the future of the university,” said Fuller. Before arriving at Pitt, Fuller earned a B.S. in Biological Systems Engineering with a Biomedical Focus and spent three years working at the National Institutes of Health (NIH) as the High-throughput and Robotics lead and bioprocess engineer at the Vaccine Research Center (VRC). “Haley has already demonstrated her leadership and commitment to service during her brief period here at the University of Pittsburgh, and resident of the community,” said Mary Besterfield-Sacre, associate dean for academic affairs and EGSO faculty mentor. “She has the self-awareness to understand the gaps in the system and speak up for those unable or too shy to do so.”
Maggie Pavlick

David Gau Receives National Cancer Center Fellowship for Kidney Cancer Research

Bioengineering

PITTSBURGH (May 18, 2020) … According to the American Cancer Society, kidney cancer is among the top ten most common cancers in men and women. More than 73,000 new cases and nearly 15,000 deaths are predicted for in the US for 2020. Clear cell renal cell carcinoma (ccRCC) -- the most common subtype of tumor associated with kidney cancer -- accounts for more than 75 percent of cases. David Gau (Math BS ‘11, BioE BS ‘11, PhD ‘18), a postdoctoral researcher at the University of Pittsburgh, will use a fellowship from the National Cancer Center to study the role of a protein in ccRCC progression. He will work with Partha Roy, associate professor of bioengineering in the Swanson School of Engineering, and Walter Storkus, professor of dermatology and immunology in the School of Medicine. “Twenty to thirty percent of patients with clear cell renal cell carcinoma will have cancer metastasis by the time of diagnosis and a third of those treated will have recurrence,” said Gau. “Our lab wants to look at the underlying mechanisms associated with this disease so that we can help develop more effective treatments.” A common theme of this type of cancer is the highly vascularized nature of the tumor environment, that is, an abundance of blood vessels in the tumor area. In this project, the research group will look at how to control a process called angiogenesis - the formation of new blood vessels. “Anti-angiogenic treatments to limit vessel formation in the tumor initially work well in patients, but many will have cancer progression due to innate resistant mechanisms to current anti-angiogenic agents,” explained Gau. “We want to evaluate the role of the protein Profilin1 in ccRCC progression.” According to Gau, current research suggests that increased Profilin1 expression in ccRCC is correlated with poor patient prognosis, and preliminary data suggests that it plays a key role in vessel formation, which would make it a candidate for a potential new therapeutic target. “Our lab has previously developed Profilin1 inhibitors, which will also be tested as a potential therapy for kidney cancer,” he said. “Completion of this project would demonstrate direct impact of Profilin1 and regulation of vessel formation in clear cell renal cell carcinoma and provide foundational evidence for targeting Profilin1 as a potential treatment for kidney cancer.” # # #

Innovating for Impact with Health Technology Entrepreneurship

Bioengineering, Student Profiles

Equipped with a degree in bioengineering, four years of research and development experience, and an award-winning design process, Jacob “Jake” Meadows (BioE ’20) is prepared to embark on a new journey to the United Kingdom, thanks to a Fulbright scholarship. Initially inspired to help individuals with fine motor control issues, Meadows and his classmate Tyler Bray (BioE ‘20) spent the last two years working on their project to help older individuals and people with movement disorders like Parkinson’s disease. “In the Art of Making course, Tyler and I learned how to create solutions to complex real-world problems with human-centered design” said Meadows, a recent University of Pittsburgh Swanson School of Engineering alumnus. “Since then, we’ve worked with over 100 individuals with Parkinson’s, physical therapists, and physicians to continue developing a wearable device that detects and alerts poor posture.” The project, Posture Protect, has since received a series of awards and funding, including Best Overall Project at the Swanson School Design Expo and first place at the Innovation Institute’s Startup Blitz. Meadows and Bray also participated in the University’s student accelerator, Blast Furnace, and were part of the first cohort of the University’s new student startup incubator, the Forge. Continuing this project outside of the classroom also motivated Meadows, Bray, and their mentor Joseph Samosky, assistant professor of bioengineering, to start Classroom to Community, a program that seeks to bridge the gap between academic projects and real-world impact. As Design & Innovation Manager, Meadows helped grow the program to support six student teams comprising more than 30 students in a collaborative community space on the fourth floor of Benedum Hall called “Studio 437.” Meadows also worked in the Department of Rehabilitation Science & Technology at Pitt, where he helped build products to improve the lives of people with physical disabilities. On campus, he was involved in student organizations and served as president of Tau Beta Pi, the engineering honor society, and as the public relations chair of the Biomedical Engineering Society. Meadows will use the Fulbright scholarship to attend University College London (UCL), where he will pursue a one-year master’s degree in entrepreneurship with the goal of starting a health technology company that focuses on healthy aging. “Studying in London, one of the world's leading centers of entrepreneurship, will empower me with an international Meadows at a user outreach session at the Fit4Boxing Gym in Allison Park after one of the RockSteady Parkinson’s Boxing classes. network of people that are excited to make health technology more accessible, affordable and effective,” said Meadows. “These relationships will enable me to begin a career dedicated to improving the lives of older individuals and people with chronic conditions through international collaboration.” He plans to connect with the Global Disability Innovation Hub, an organization at UCL whose goal is to challenge how the world thinks about disability through co-design, collaboration and innovation. He will also continue participating in the “maker movement” by joining UCL’s Institute of Making. “I care a lot about inclusive design, and I am excited to continue promoting it in both engineering and entrepreneurship,” he said. Meadows’ creativity doesn’t stop at health technology design. In addition to his studies, he hopes to explore different regions of the U.K. and continue to practice another passion -- photography. “I am excited to explore the culture, architecture and landscapes of the United Kingdom through the lens of my camera alongside fellow photographers I meet in Britain,” he said. When Meadows returns to the U.S., he plans to continue addressing issues in aging by starting a health technology company that will combine empathetic design and advanced technologies to benefit the public good. He hopes that this experience will give him the global perspective needed to apply different approaches to medical care and help individuals age in a healthy way. “My studies in the UK will ultimately help me promote the global shift in health technology from expensive and intimidating to affordable and empowering,” he said. # # #

Giving Distressed Lungs a Safer Fighting Chance

Covid-19, Bioengineering, Chemical & Petroleum

PITTSBURGH (April 27, 2020) … A device designed at the University of Pittsburgh could help improve outcomes as a treatment for COVID-19 when used in conjunction with non-invasive or mechanical ventilation, and it recently received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration. Health records from a New York study showed that close to 90 percent of patients who were placed on mechanical ventilation did not survive.1 Some intensive care units are now considering mechanical ventilation as a last resort because of the complications and side effects associated with the process, and researchers believe this device could help. The Hemolung® Respiratory Assist System is a minimally invasive device that does the work of the lungs by removing carbon dioxide directly from the blood, much as a dialysis machine does the work of the kidneys. The device was developed by William Federspiel, PhD, professor of bioengineering at Pitt’s Swanson School of Engineering, and the Pittsburgh-based lung-assist device company ALung Technologies, co-founded by Federspiel. A public health emergency related to COVID-19 was declared by the Secretary of Health and Human Services on February 4, 2020, and the FDA issued ALung the EUA to treat lung failure caused by the disease. Hemolung could help eliminate damage to the lungs caused by ventilators and does not require intubation or sedation, which allows patients to remain mobile during treatment. “Ventilation can cause serious issues in lungs that are already being damaged by the disease itself,” said Federspiel. “The Hemolung would allow the lung to rest and heal during the ventilation process by allowing for gentler ventilation. It could also prevent certain patients, who have less severe symptoms, from having to go on ventilation in the first place.” Mechanical ventilation requires patients to be sedated and intubated, and a myriad of complications can arise from the treatment, including collapsed lung, alveolar damage, and ventilator-associated pneumonia. For these more critically ill patients, the Hemolung could be used to help remove CO2, which would allow the mechanical ventilation process to be done more gently. Before resorting to mechanical ventilation, less severe COVID-19 cases can use non-invasive ventilation, which uses a mask to help support breathing, but sometimes this treatment is not sufficient. In this case, the Hemolung device could be used to support the non-invasive methods and prevent mechanical ventilation altogether. Peter M. DeComo, Chairman and CEO of ALung Technologies, stated, “With published mortality rates as high as 90% for patients receiving invasive mechanical ventilation (IMV), we believe that the Hemolung can be a valuable tool for physicians to be used in conjunction with IMV, by reducing or eliminating the potential of further lung damage caused by high ventilator driving pressures, often referred to as Ventilator Induced Lung Injury. Many of the academic medical centers involved with our clinical trial have already requested the use of the Hemolung RAS for treatment of their COVID-19 patients.” Created to help chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS) patients, Hemolung has already been used on thousands of patients in Europe, where it was approved in 2013, and it is currently in clinical trials in the United States. Since the onset of the pandemic, the device has been used on some COVID-19 patients with success; however, set-up of the Hemolung is not trivial. Medical professionals would need to be trained to use the technology, and it would take time to supply a significant number of devices. Federspiel also holds appointments in the School of Medicine and the McGowan Institute for Regenerative Medicine (MIRM) at Pitt and is a Fellow of the National Academy of Inventors. “This technology developed by Dr. Federspiel and ALung Technologies is a perfect example of how collaborative research at the McGowan Institute can impact human lives,” said William Wagner, director of MIRM and professor of surgery, bioengineering and chemical engineering at Pitt. “A clinical viewpoint is necessary, but medical training doesn’t give you an engineer’s perspective of design and manufacturing. You need a solid foot in both camps to make progress.” # # # 1: Most COVID-19 Patients Placed on Ventilators Died, New York Study Shows, https://www.usnews.com/news/health-news/articles/2020-04-22/most-covid-19-patients-placed-on-ventilators-died-new-york-study-shows

Twelve Pitt Students Awarded 2020 National Science Foundation Graduate Research Fellowships

All SSoE News, Bioengineering, Chemical & Petroleum, Electrical & Computer, MEMS

PITTSBURGH (April 20, 2020) … Twelve University of Pittsburgh students were awarded a 2020 National Science Foundation Graduate Research Fellowship. This is the highest number of students to receive this competitive award since 2015 when the University had a total of 13 recipients. An additional sixteen Pitt students also earned an honorable mention. For the past two years, the University’s Honors College has been working with the Office of the Provost to host informational workshops and boost participation in the fellowship program. Patrick Loughlin, professor of bioengineering, also holds workshops in the Swanson School of Engineering to encourage graduate students to apply to external fellowships. The NSF Graduate Research Fellowship Program (GRFP) is designed to ensure the vitality and diversity of the scientific and engineering workforce in the United States. GRFP supports the graduate study of U.S. citizens, nationals and permanent residents attaining research-based master's and doctoral degrees in science, technology, engineering and mathematics (STEM) or in STEM education at institutions located in the United States. Fellows receive a three-year annual stipend of $34,000 as well as a $12,000 cost-of-education allowance for tuition and fees. Four Swanson School students and three alumni are among this year’s cohort. Three current students and three alumni received honorable mentions. Award Recipients Janet Canady, a bioengineering undergraduate, works in Dr. George Stetten’s lab where she helps design and test FingerSight, a device for the visually impaired. Zachary Fritts, a bioengineering undergraduate, works in Dr. Tamer Ibrahim’s lab where he helps design and build multi-channel transmit arrays for ultra-high field magnetic resonance imaging (MRI). Brian Gentry, a mechanical engineering undergraduate, works in Dr. John Keith’s lab where he investigates local solvent effects on density functional theory energy calculations applied to a class of organic compounds called chelating agents. Evan Miu, a chemical engineering graduate student, works with Drs. James R. McKone and Giannis Mpourmpakis. His research explores combined thermo- and electro-catalytic processes through experimental electrochemistry and density functional theory. Honorable Mentions Evan Becker, an electrical and computer engineering undergraduate, works in Dr. Natasa Miskov-Zivanov’s lab where he has designed representation schemes for modeling and simulating dynamic behavior in systems such as intracellular networks and geopolitical systems. Dr. Miskov-Zivanov’s lab uses discrete logic techniques, allowing him to rapidly assemble these models from scientific literature. Alexander Maldonado, a chemical engineering graduate student, works in Dr. John Keith’s lab to develop novel ways to accurately and quickly predict how complicated chemical reactions occur in solvents using state-of-the-art quantum chemistry and machine learning. Jordyn Ting, a bioengineering graduate student, works in the Rehab Neural Engineering Labs with Dr. Douglas Weber where her work focuses on investigating the spared connection between the motor cortex and muscles. Swanson School alumni Kiara Lee (BioE, Brown University), Harrison Douglas (ChemE, Michigan State University) and Katarina Klett (BioE, Stanford University) also received awards. The alumni to receive honorable mentions include Katreena Thomas (IE, Arizona State University), Richard Hollenbach (MEMS, Duke University) and Arjun Acharya (BioE, University of Utah). # # #

Peering Into Undergraduate Research at Pitt: Swanson School of Engineering Publishes Sixth Edition of Ingenium

All SSoE News, Bioengineering, Chemical & Petroleum, Civil & Environmental, Electrical & Computer, Industrial, MEMS, Student Profiles

PITTSBURGH (April 15, 2020) … Demonstrating the diverse and exceptional undergraduate research in the University of Pittsburgh Swanson School of Engineering, Associate Dean for Research David A. Vorp recently released the sixth edition of Ingenium. This edition features a collection of 26 articles that highlight work performed throughout the 2019-20 academic year and during the school’s 2019 summer research program. Ingenium mirrors the peer-review process of scientific journals by inviting undergraduate researchers to submit manuscripts to a board of graduate students. The review board provides feedback to which the undergraduates are required to respond before their work is accepted. The co-editors-in-chief for this edition were Monica Liu, a bioengineering graduate student, and Jianan Jian, an electrical and computer engineering graduate student. “I think Ingenium is a great experience for undergraduates,” said Liu. “They have been diligently working on research all year, and Ingenium is a great way for them to present it to a larger audience and get experience writing a scientific paper.” While the publication is designed to help prepare undergraduates, members of the graduate review board also benefit from a different point of view in the academic writing process. “Graduate students spend so much time writing about their research and incorporating feedback,” said Liu. “Ingenium is a great way to experience the other side of things -- taking the time to review others' work gives us a broader perspective when we review our own work.” Ingenium features research from each department in the Swanson School and is divided into five categories: experimental research, computational research, device design, methods, and review. The publication is sponsored by the school’s Office of Research. “With each year and with each edition of Ingenium, we continue to see notable and impressive academic and professional growth and development in our undergraduate students when given opportunities to engage in scientific research,” said Vorp. “We witness students taking the knowledge, skills, and information that they learn in their coursework and apply it in a meaningful and intentional manner outside of the classroom. These thriving students are our future -- of both our highly accredited institution and our world.” ###

Pitt Makerspace Creates Open Source Face Shield to Fill Local PPE Need

Covid-19, Bioengineering, MEMS, Student Profiles

PITTSBURGH (April 7, 2020) — The shortage of personal protective equipment (PPE) caused by the spread of the coronavirus has inspired a fleet of makers in the community to pitch in and make items like masks and face shields to be used in hospitals. The Pitt Makerspace at the University of Pittsburgh Swanson School of Engineering is no exception—a team there has partnered with a local printing company and the UPMC 3D Print Lab to create a single material plastic shield, and they have made the details free for anyone to use. The project was led by Brandon Barber, the design, innovation and outreach coordinator in the Department of Bioengineering at Pitt, and Dan Yates (BSME ’19), innovation project coordinator for the Pitt Makerspace. The Pitt team worked closely with Ken Mattheis and Steve Reed from the Pittsburgh-based printers Reed & Witting to develop the design, and they utilized input from medical professions to ensure the shields would meet their needs. Single material face shield on a mannequin head. The shields are made of a single piece of material and are then folded into place to form the shield; because of this, can be made with any thin, clear plastic and do not require any other materials, like foam or elastic. They were designed with high-volume die-cutting in mind, and many commercial print shops already have the equipment and materials to make thousands of these shields in a short period of time, according to Barber. Reed & Witting is set to make as many as 5,000 shields a day. “We were inspired to act when we saw the shortage of PPE in our community and realized how impactful something like this could be,” said Barber. “The Makerspace is all about finding innovative designs that positively influence the world around us, and we hope that’s what we have been able to do with this project.” You can find the open source face shield here. ### The Pitt Face Shield has not been medically certified for use as PPE. The creators make no warranties of any kind (express or implied) relating to accuracy, usefulness, usability, marketability, performance, or otherwise of the content release.

Two Swanson School Projects Win University of Pittsburgh Scaling Grants

Bioengineering, Chemical & Petroleum, Civil & Environmental

PITTSBURGH (April 6, 2020) — Two projects from the Swanson School of Engineering have received University of Pittsburgh Scaling Grants.The first, tackling the global problem of plastic waste, is headed by Eric Beckman, PhD, Bevier Professor of Chemical and Petroleum Engineering and co-director of the Mascaro Center for Sustainable Innovation. The second project, which will support the push for artificial intelligence innovation in medical imaging, was also awarded a Scaling Grant and is led by Shandong Wu, PhD, associate professor in the Department of Radiology. The Scaling Grants provide $400,000 over two years to support detailed project planning, gathering proof-of-concept results, and reduction of technical risk for teams pursuing an identified large extramural funding opportunity. The Scaling Grants are part of the University’s Pitt Momentum Funds, which offer funding across multiple stages of large, ambitious projects. Addressing the Global Waste Challenge The problem of plastic waste is growing on a global scale, with an annual global production rate of more than 500 million tons per year and predicted to triple by 2036. The project, “Attacking the Global Plastics Waste Problem,” seeks to create a convergent academic center welcoming expertise from across the University that will focus on the circular economy as a solution. “For most new technologies, one group creates the technology in the lab as a pilot, then at full scale. The group launches it, and only later decides if there are environmental and/or policy and/or legal issues,” says Beckman. “We're proposing to do these analyses in parallel, so that each section of the work informs the others. Further, the technology we are proposing to develop is a mixture of chemical engineering, chemistry, and materials science.” The interdisciplinary team will take advantage of its deep expertise in both the science of plast ics recycling and the legal and governance frameworks that will help governments implement a circular economy for plastics. In addition to Beckman, the team consists of Melissa Bilec, PhD, Roberta A. Luxbacher Faculty Fellow, associate professor in civil and environmental engineering (CEE), and deputy director of MCSI; Vikas Khanna, PhD, Wellington C. Carl Faculty Fellow and associate professor in CEE and Chemical and Petroleum Engineering; Gotz Veser, PhD, professor in chemical and petroleum engineering; Peng Liu, PhD, associate professor in the Department of Chemistry; Amy Wildermuth, professor and dean of the University of Pittsburgh School of Law; and Joshua Galperin, visiting associate professor in the School of Law. “Recycling can only do so much. A circular economy framework is a promising solution to the complex, urgent problem that plastic pollution presents,” says Bilec, who is part of a five-university team that received a two-year National Science Foundation grant for $1.3 million to pursue convergence research on the circular economy as a plastic waste solution. “Our proposed center will integrate the science and engineering of plastics recycling, using a novel approach on both the recycling and manufacturing sides, into frameworks tracking its environmental and economic impact.” Applying Artificial Intelligence to Medical Research The second project to receive a Scaling Grant is the “Pittsburgh Center for Artificial Intelligence Innovation in Medical Imaging,” a collaboration between the Departments of Radiology, Bioengineering, Biomedical Informatics, and Computer Science. This work, led by Wu, aims to use artificial intelligence (AI) to reshape medical imaging in radiology and pathology. Through the Pittsburgh Health and Data Alliance, the region is already at work using machine learning to translate “big data” generated in health care to treatments and services that could benefit human health. "The advancement in AI, especially in deep learning, provides a powerful approach for machine learning on big healthcare data,” said Wu. “Deep learning enables large-scale data mining with substantially increased accuracy and efficiency in data analysis." The multidisciplinary research team will work to develop AI imaging methodology and translational applications with the ultimate goal of creating tools that are clinically useful, accurate, explainable and safe. “AI can substantially improve quantitative analysis to medical imaging data and computational modeling of clinical tasks using medical images for disease diagnosis and outcome prediction," explained Wu. David A. Vorp, associate dean for research and John. A. Swanson Professor of Bioengineering, will help facilitate this collaboration in engineering. “Artificial intelligence nicely complements bioengineering and medical research,” said Vorp. “My lab uses AI with CT scans to help predict the prognosis and improve treatment of aortic aneurysm, and that is just one example of how this cutting-edge technology can be applied to medical images. Rather than relying on the naked eye, we can use AI to analyze these images and have a more sensitive detector to identify disease, improve health and save lives.” The group’s long-term vision is to combine the computational expertise and clinical resources across Pitt, UPMC and Carnegie Mellon University to build a center for innovative AI in clinical translational medical imaging. ###
Maggie Pavlick and Leah Russell

Engineering Technology to Explore the Human Mind

Bioengineering

The brain is the most complex organ in the human body. At a mere three pounds, it is a workhorse that controls fundamental aspects of human life, such as movement, sensation, memory, and other involuntary processes in the body. In addition, the brain helps make us who we are: it controls our emotions, personality, language, and behavior. Despite being a crucial organ, a comprehensive understanding of the brain is still elusive. Technology developed in the Swanson School of Engineering’s Radiofrequency (RF) Research Facility allows researchers at the University of Pittsburgh to harness the power of one of the strongest human magnetic resonance imaging (MRI) systems. These imaging advancements have illuminated details of brain structure and function that are not visible on standard MRI devices, and researchers now want to study what these images can reveal about the human mind. Getting a Better Look at the Brain The Radiofrequency (RF) Research Facility at the University of Pittsburgh traces its roots to Professor of Bioengineering Tamer Ibrahim’s doctoral work at the Ohio State University, where he designed antennas and coils to address challenges with ultrahigh field MRI imaging. At Pitt, the RF Research Facility and the 7 Tesla (7T) Bioengineering Research Program heavily utilize a 7T human MRI – one of the most powerful imaging devices in the world. “As MRI technology continues to become more powerful, the challenges associated with ultrahigh field imaging are exacerbated,” said Ibrahim. “The increased frequency of imaging at 7 Tesla can cause image inhomogeneities and heat to concentrate at certain locations in the head due to the presence of nonuniform electromagnetic fields. My lab works on designing and constructing devices that smooth those fields to improve the image quality and safety, and thereby, the utility of 7 Tesla Human MRI.” The RF Research Facility created a “Tic-Tac-Toe” RF coil system of antennas that are tightly and uniquely arranged to fit the human head.  It was designed through extensive computer simulations using full wave electromagnetic software developed in the lab to optimize the antenna configuration.  The resulting device solves many of the issues associated with ultrahigh field MRIs, giving Pitt an edge in the field of neural imaging. “Our coil system is a novel design that improves homogeneity, reduces power depositions in tissue, increases the speed of acquisition, and enhances resolution, not just in space, but also in time,” said Ibrahim. “We are able to provide superior neural imaging capabilities, which opens a lot of avenues to explore things unknown.” Ibrahim has used this unique technology to establish interdisciplinary collaborations across the University, in particular with Pitt’s Department of Psychiatry. A Glance Inside the Human Mind Just across the street from the Benedum Hall, where bioengineering resides, is the Western Psychiatric Hospital of the University of Pittsburgh Medical Center (UPMC) - home to the Department of Psychiatry. In recent years, mental health research has become more dependent on imaging, and this work at Pitt has been enhanced with the technology developed by the RF Research Facility. “At the broadest level, the problems of psychiatry are based in the complexity of the human brain,” said David Lewis, distinguished professor of psychiatry and neuroscience and chair of psychiatry. “The human brain is, without question, the most complex biological organ in the known universe, and psychiatric illnesses affect the most sophisticated functions of that most complex organ.” One of Ibrahim’s frequent collaborators is Howard Aizenstein, Charles F. Reynolds III and Ellen G. Detlefsen Endowed Chair of Geriatric Psychiatry at Pitt, whose research primarily looks at older adults with depression, cognitive impairment, and dementia. Aizenstein said, “Tamer’s technology has been helpful in moving this research forward because the key challenge in studying the aging brain and the neuropathological changes in aging is to look at the small vessels.” Prior to the development of 7T MRI and Ibrahim’s technology, researchers had to rely on 1.5T or 3T images to see mechanistic changes in human disease, but with Ibrahim’s coil, they can now get a more in-depth look into how the brain works. “Tamer’s 7T head coil allows you to see with much higher contrast very small microstructural changes that you couldn’t see with standard MRI,” explained Aizenstein. “This is really helpful in emerging models of Alzheimer’s disease because we think these small vessels play a big role. We also believe that accelerated aging is part of both depression and Alzheimer’s disease, and this technology allows us to better understand it.” 7T MRI was approved for clinical applications by the U.S. Food and Drug Administration in October 2017, which is a pivotal development for Ibrahim’s lab. His group has performed more than 1000 scans using the Tic-Tac-Toe RF coil system on patients/subjects, and with more than $35 million in total funding that utilizes this technology, they have budgeted another 2500 scans for various neurological and epidemiological studies. “Our work is quite advanced in the translational aspect of research,” Ibrahim said. “Everything we do in the lab is applied to patient studies and is impacting the lives of people. No one is using 7T imaging the way we are doing it here at Pitt.” The University has 20 active NIH research grants using this technology. The majority of these are collaborations between bioengineering and psychiatry, so in an effort to formalize this connection, Ibrahim and Aizenstein reached out to the National Institute for Mental Health (NIMH) for support to develop a predoctoral training program. Bridging Two Fields Ibrahim and Aizenstein recently received a $1.1 million grant from the NIMH to develop a unique multidisciplinary training program that prepares students with a background in engineering and other quantitative sciences for careers in mental health research. The NIMH wants to transform mental health care and recently published a strategic plan that, in part, seeks to develop new tools from the BRAIN initiative, apply computational approaches that may provide novel ways to understand relationships among datasets, and develop new and competing applications that target the NIMH research priority areas. Pitt Bioengineering and Psychiatry, two nationally ranked departments, will join forces to train a new generation of students with a focus on both bioengineering and psychiatric research. By tapping into both quantitative and qualitative data, they hope that this training grant will forge collaborations, stimulate research in each field, and further strengthen the University’s leadership in biomedical and psychiatric research, with the ultimate goal of benefitting the human condition. “Psychiatry is a field that has not been traditionally quantitative,” said Ibrahim, “and engineering is the opposite so I think there is a clear marriage between the two.” Predoctoral trainees in this program will benefit from a dual mentorship with advisors from both the Swanson School of Engineering and the School of Medicine. Their research will focus on neuroimaging, neurostimulation, and neural engineering - all of which are widely used in mental health research including mood disorder, anxiety disorder, psychotic disorder, suicide, and cognitive impairment. “With interdisciplinary work, there’s effort that comes with learning to speak to each other and appreciating other perspectives,” Aizenstein said, “but there is so much you gain from it, and that’s where it’s beneficial and fun.” The announcement of this program has already sparked new collaborations between bioengineering and psychiatry, and the department leadership hopes that these collaborations will continue to grow and benefit both areas. “This program will help stimulate the field of bioengineering given the complexity of the challenges in psychiatric research,” said Lewis. “I’m also hopeful that the collaborations and new investigators that emerge as the product of this program will, by harnessing complex datasets and new technologies, enhance precision medicine, create novel therapeutics and improve the clinical practice of psychiatry.” “Tamer’s work and this unique collaboration with psychiatry puts Pittsburgh in a great position to become a leader in neural imaging,” said Sanjeev Shroff, distinguished professor and Gerald E. McGinnis Chair of Bioengineering. “I strongly believe that this training program will create a new breed of investigator who can tackle the fundamental biological questions in psychiatry using engineering (quantitative) approaches and I look forward to seeing how these collaborations will expand and produce cutting-edge research.” # # #

Thanks for Tuning In: Swanson School Students Present Virtual Dissertation Defenses

Covid-19, Bioengineering, Electrical & Computer, Student Profiles

PITTSBURGH (March 30, 2020) … After years of classwork, conducting research, collecting results and attempting to publish in peer-reviewed journals, Gary Yu was finally ready to present his dissertation defense to his committee members. He got dressed, confidently entered the room, signed in to Microsoft Teams, and began the virtual meeting. In the days of social isolation during the coronavirus pandemic, this was the only way for Yu, an MD/PhD student in the Department of Bioengineering, to complete the PhD portion of his degree on schedule. Yu is not alone. Across the University, graduate students find themselves reaching long-anticipated academic milestones alone, at home, behind a computer monitor. However, even under these unusual conditions, they are making the best of it - and succeeding. Yu’s presentation started with an introduction from his advisor, John Pacella, associate professor of medicine and bioengineering. The audience then fell silent as they muted their microphones to avoid interruptions and turned off their cameras to save bandwidth. According to Yu, this absence of communication was one of the main challenges in defending remotely. “Usually when I present, I'm reassured by eye contact and other gestures of understanding that my audience is paying attention,” he said. “When I was presenting my dissertation, there were moments where I had doubts creep up in the back of my mind. Since it was completely silent, aside from myself, I wondered whether I had lagged out or disconnected from the call because of computer or internet issues.” Yu continued to present his work on a new microbubble contrast agent with anti-inflammatory properties that can be used with therapeutic ultrasound pulses to treat cardiovascular disease. He recalled a moment of relief after an audience member broke the silence by opening a bag of chips on the other end. He eventually adapted to this new environment and noticed that he began to pick up online vernacular as he subconsciously quipped, “Thanks for tuning in,” at the end of his presentation. After his committee members took turns asking questions, they informed Yu that he successfully passed his defense. Mohammed Sleiman, too, successfully defended his thesis virtually. His advisor, Brandon Grainger, created two “rooms” in Zoom, inviting Sleiman to one and using the second for committee discussion after the defense. Despite the unusual circumstances, Sleiman, who was studying the energy conversion process in electric vehicles, passed with flying colors and earned his MS in electrical engineering. Grainger is an Eaton Faculty Fellow, assistant professor of electrical and computer engineering, and associate director of the Swanson School’s Electric Power Engineering program. “After a few minutes in the other room, the committee came back to my Zoom room and announced my pass!” recalled Sleiman. “It was a thrilling experience to present to professors online. The sad thing is that I missed taking photos for memories with them, because we were far away.” Grainger, too, noted that one downside of virtual defenses is the absence of in-person celebration with mentors, friends and loved ones that usually comes after them. “The online defense is a bit abnormal, but Mohammed handled the challenges well,” said Grainger. “When a defense is live, in a conference room, the room is typically filled with labmates, friends, and sometimes family, but having a virtual meeting did not allow for this to happen.” Despite the unusual circumstances, both Yu and Sleiman were able to make the best of their experiences. The necessity of social distancing did not stop Sleiman from celebrating; after he heard the news that he passed, he headed to the Cathedral of Learning, still in his suit, to snap a few photos to commemorate the moment for social media. Yu, too, did his best to embrace the quirks of presenting to an audience you cannot see. “Don't be nervous about the silence you will likely encounter,” suggested Yu. “Do your best to have good sound quality and minimize background noise. Enjoy feeling like a Youtuber or an academic streamer, and make sure to celebrate - responsibly - after your defense!” If you find yourself preparing for a virtual defense, here are some tips to make the best of it: Find a good streaming platform. Swanson School students have successfully used Microsoft Teams and Zoom. Consider having your audience turn off video to avoid overwhelming the connection. Ask the audience to remain muted when they are not contributing to the discussion. This will decrease background noise and feedback. Work with your advisor to test your technology ahead of time to make sure you have everything you need. Make sure to be comfortable and have hydration close by! # # #
Maggie Pavlick and Leah Russell

Ameya Nanivadekar Selected for NIH Outstanding Scholar in Neuroscience Award Program

Bioengineering, Student Profiles

PITTSBURGH (Mar. 19, 2020) … University of Pittsburgh graduate student Ameya Nanivadekar was selected by the National Institutes of Health (NIH) as a recipient of the Outstanding Scholar in Neuroscience Award Program. This new offering from the NIH recognizes and supports individuals who are conducting exceptional research and have a great academic potential in their scientific PhD programs. Nanivadekar is a bioengineering PhD student at the Swanson School of Engineering who works in the Rehab Neural Engineering Labs under the direction of Lee Fisher, assistant professor of physical medicine and rehabilitation. His research focuses on electrical stimulation of the spinal cord to deliver a sense of touch in upper and lower limb amputees. “Nearly 200,000 Americans undergo amputation each year, yet the acceptance rate of prosthetic limbs is less than 40 percent,” explained Nanivadekar. “This low rate is in part due to the lack of sensory feedback - such as the sense of touch - in existing prostheses. My research aims to better understand the response to electrical stimulation and how we can incorporate sensory feedback into modern prostheses.” Nanivadekar has worked on evaluating the performance of novel electrodes, building computational models to study how stimulation recruits neurons and affects tissue in the spinal cord, and conducting human experiments to study the kinds of sensations that can be produced through electrical stimulation of the spinal cord. “The ultimate goal of this work is to provide sensory feedback that can improve the functionality of a prosthesis for activities such as maintaining balance while standing or walking or grasping and interacting with objects,” he said. Nanivadekar was previously an ARCS Scholar, which is a program from the ARCS Foundation that provides unrestricted funding to help the country's brightest graduate and undergraduate students create new knowledge and innovative technologies. “I'm proud of Ameya's accomplishments working to improve the lives of people with limb amputations,” said Fisher. “He is a truly exceptional student and an instrumental member of our lab. This award is well-deserved." # # #

Madeline Cramer receives NIH F31 award for regenerative medicine research

Bioengineering, Student Profiles

PITTSBURGH (Mar. 16, 2020) … University of Pittsburgh graduate student Madeline Cramer received an F31 award from the National Institutes of Health for her regenerative medicine research that may help improve outcomes in cardiac disease. Cramer studies bioengineering in the Swanson School of Engineering and works in the lab of Stephen Badylak, professor of surgery at Pitt and deputy director of the McGowan Institute of Regenerative Medicine. Badylak’s lab focuses on the use of biologic scaffolds composed of extracellular matrix (ECM) to facilitate functional tissue and organ reconstruction. Present within all tissues and organs, ECM provides essential structural support and also initiates biochemical and biomechanical cues. Cramer’s project will look at myocardial infarction (MI) and examine how a specific protein embedded within the ECM may affect the underlying mechanisms behind the scaffold’s therapeutic response. “Following myocardial infarction, cardiomyocyte death initiates an intense inflammatory response which is necessary to clear the debris of the dead cells,” explained Cramer. “However, a prolonged pro-inflammatory state is associated with immune-driven fibrosis that can progress to heart failure.” Heart failure is a costly condition that affects millions of adults in the United States. Tissue engineered biologic scaffolds derived from ECM have been shown to promote an anti-inflammatory phenotype in macrophages and reduce fibrosis after MI in pre-clinical and clinical studies, but the underlying mechanisms driving this response are only partially understood. “Previous work in the Badylak lab showed that ECM is an abundant source of extra-nuclear interleukin-33 (IL-33), a protein that is stored and protected from degradation within matrix-bound nanovesicles (MBV),” said Cramer. “My research aims to delineate the roles of MBV-associated IL-33 in mediating the pro-remodeling effects of ECM through in vitro and in vivo models of myocardial infarction.”\ Demonstrating that IL-33 containing MBV can dampen the fibrotic response following MI may prove to be a significant advancement in the treatment of MI and the prevention of subsequent heart failure. “Maddie has worked extremely hard and is very deserving of this award,” said Dr. Badylak. “I’m confident that the results of her work will have a significant impact upon the field.” # # #

Four Members of the Swanson School are Recognized by the Carnegie Science Awards

Bioengineering, Civil & Environmental, Student Profiles

PITTSBURGH (Mar. 11, 2020) … Four members of the University of Pittsburgh Swanson School of Engineering were recognized by the Carnegie Science Awards, announced on March 10 by the Carnegie Science Center. Bioengineering’s Bryan Brown and Alexis Nolfi received the Postsecondary Educator Award and University Student Award, respectively. Civil and environmental engineering’s David Sanchez and Kareem Rabbat received honorable mentions in the same categories. They will receive the awards at the 24th Annual Carnegie Science Awards Celebration, held May 8, 2020. Bryan Brown, associate professor of bioengineering, Postsecondary Educator Award Brown’s educational efforts in the Department of Bioengineering include teaching and mentoring junior faculty, postdoctoral fellows, and graduate students. He also serves as the director of educational outreach at the McGowan Institute for Regenerative Medicine, where he reaches younger audiences through the McGowan Institute’s Summer School. In July 2014, Brown organized and launched the program, which is a hands-on experiential learning program that aims to provide regional, national, and international students an opportunity to explore the multidisciplinary field of regenerative medicine. Through lectures and laboratory experiences, undergraduate students have the opportunity to interact with more than 20 faculty members from across the University. The program aims to recruit students from underrepresented backgrounds, including those from universities that lack significant bioengineering and/or regenerative medicine programs. In addition to engaging younger audiences in STEM, Brown also targets individuals who wish to continue their education through his course on regenerative medicine hosted by Carnegie Mellon University’s Osher Center for Lifelong Learning program. As an extension of these activities, he also developed an hour long “Open to the Public” session on the “Hype vs. Hope of Stem Cells and Regenerative Medicine,” which focuses on the realities of the science and clinical practice related to the use of stem cells in medicine. The program was developed to address the most common questions asked by participants in the Osher classes. Alexis Nolfi, bioengineering graduate student, College Student Award Nolfi is involved in numerous projects centered on how the immune system is involved in the pathogenesis of disease and how we can modify immune response to biomaterials and with biomaterials-based approaches. Much of her work has a distinct focus in women’s health applications, including a polypropylene mesh often used in pelvic surgery and a novel ovarian hydrogel that could one day be used to generate a tissue-appropriate model of endometriosis. According to Nolfi, the field of basic science research in women’s health topics is underserved by the biomaterials and regenerative medicine community. She believes that this research helps to shine light on topics deserving of more attention, and the experimental findings and developments will be applicable to not only biomaterials-based urogynecologic applications, but also to furthering advancement of other biomaterial and immunology-based fields. As part of her work with biomaterials, she and the lab developed a novel contact lens that is coated with an immune modifying molecule for the treatment of dry eye disease. The bioengineering- and opthamology-led research group was recently awarded $100,000 at the 2019 Pitt Innovation Challenge. David Sanchez, assistant professor of civil and environmental engineering, Postsecondary Educator honorable mention In addition to his appointment in CEE, Sanchez serves as assistant director of the Mascaro Center for Sustainable Innovation. He directs programs including the Undergraduate Summer Research Program, Sustainability certificate, and Master’s in Sustainable Engineering. He is the founding advisor for Pitt Hydroponics and the principal investigator for Sustainable Design Labs. He teaches the Environmental Engineering Lab, core engineering sustainability courses, and in the First Year Engineering program. Sanchez also leads many community engagement efforts. For the past five years, he has held a Summer Teacher workshop that exposes middle school science teachers to sustainability and engineering. This effort indirectly engages around 2000 students each year. He founded the Constellation Energy Inventor Labs and has used it to teach hundreds of Pittsburgh area students about energy using design-build modules. Furthermore, he has worked with the ALCOSAN summer science program for many years and helped create the Clean Water Academy for 2018. Sanchez organizes an annual Makerspace and Mindsets Bootcamp each fall that introduces engineering students to the creative resources available to them and the design thinking that goes with them. He was the recipient of the Swanson School’s Faculty Diversity Award in 2015 in recognition of his significant contributions in increasing diversity. His research focuses on sustainable solutions to pollution, including a recent $420,000 NSF grant to study biofilms grown on electrodes as a method to degrade the contaminant Bisphenol A (BPA). Kareem Rabbat, undergraduate senior in civil and environmental engineering, College Student honorable mention Rabbat’s passion for the environment is clear to anyone he meets. Through research, coursework, internships, competitions and global summits, he has taken full advantage of his four years at Pitt and does not plan to slow down in his pursuit to educate communities about sustainability and develop technology that helps guide a greener future. From an aquaponics project funded by the competitive Ford College Community Challenge sprouted Ecotone Renewables, a company dedicated to local and sustainable urban farming. Rabbat is CIO of the company which has converted shipping containers into biodigesters and greenhouses throughout the city. They also seek to educate the local communities about sustainable practices of agriculture. This past summer, he performed research looking for bacteria and fungi that could solve persistent pollution problems. If successful, the innovation could be used globally to eliminate toxicity caused by nonylphenol and bisphenol (BPA) that contaminate soil and water near old industrial facilities. Rabbat’s environmental work does not end at Pittsburgh’s city limits. In addition to his local achievements, Kareem has also explored global sustainability: he designed and implemented aquaponics/hydroponics systems in Brazil; he studied abroad in Johannesburg, South Africa as part of the Swanson School’s Engineering Design for Social Change program; and he was recently nominated and selected to attend the 2019 Global Grand Challenges Summit Student Competition in London, a program held jointly by the U.S., U.K., and Chinese academies of engineering. His achievements have been recognized locally by the Incline’s Who’s Next: Environment and Energy Class of 2019. # # #

Learn more about Pitt's planning and response to COVID-19

Bioengineering, Chemical & Petroleum, Civil & Environmental, Electrical & Computer, Industrial, MEMS, Diversity, Student Profiles, Office of Development & Alumni Affairs

Please visit and bookmark the University of Pittsburgh COVID-19 site for the most up-to-date information and a full list of resources. From the University Times: As the coronavirus COVID-19 continues to spread around the world, Pitt is remaining diligent with addressing related issues as the pop up. For an overall look at updates from Pitt, go to emergency.pitt.edu. On Saturday, Provost Ann Cudd issued a statement about how to support faculty and staff who have committed to attending professional conferences this semester and choose not to attend due to the COVID-19 outbreak. The University will grant an exception for travel booked through May 31 and reimburse any out-of-pocket expenses incurred by those who decide to cancel travel. The administration will reassess this deadline date as COVID-19 evolves and may extend the deadline as conditions evolve. For more updates from the provost, go to provost.pitt.edu. The provost and the University Center for Teaching and Learning is encouraging faculty to be prepared if remote learning situations become required. The center has set up a page detailing the basics of providing instructional continuity. The page will be updated regularly. Find information about remote learning and more at teaching.pitt.edu/instructional-continuity. All business units and responsibilities centers also are being asked to work on how to handle mass absenteeism and/or the need for as many people as possible to work at home.

Postdoctoral Position in Cancer Bioengineering - Zervantonakis lab

Bioengineering, Open Positions

A postdoctoral position is available at the Tumor Microenvironment Engineering lab in the Department of Bioengineering and UPMC Cancer Institute. We employ a quantitative approach that integrates microfluidics, systems biology modeling, and in vivo experiments to investigate the role of the tumor microenvironment on breast and ovarian cancer growth, metastasis and drug resistance. Our group has projects in three main areas: (1)  Drug-resistant microenvironments in breast cancer: modeling cellular dynamics. (2)  Metastatic dissemination in ovarian cancer: macrophages and fluid flow. (3) Localized drug release technologies and single-cell functional assays. Applicants should hold a PhD in bioengineering, biomedical sciences or related fields. A strong background in cancer biology is preferred, including experience with quantitative assay development and optimization, microscopy. Openings are also available for candidates with a computational/mathematical background with expertise in mechanistic modeling and systems analysis. The Tumor Microenvironment Engineering laboratory offers the opportunity to work at the forefront of cancer bioengineering, learn cutting edge techniques and collaborate with an interdisciplinary group of scientists and clinicians. The candidate will benefit from the rich biomedical research environment in the University of Pittsburgh, including the UPMC Hillman Cancer Center, the Department of Computational and Systems Biology, the Drug Discovery Institute and the Magee-Women’s Research Institute. The city of Pittsburgh is one of the “most livable” cities in the US and is a leader in medicine, engineering and high-tech industries. Openings are available starting April 2020. Please visit the website (www.zervalab.com) to find out more about research projects, publications, mentoring and collaborations. Interested applicants please submit a CV, statement of research interests and contact information for three references to: Ioannis Zervantonakis, Assistant Professor ioz1@pitt.edu. The Department of Bioengineering is strongly committed to a diverse academic environment and places high priority on attracting female and underrepresented minority candidates. We strongly encourage candidates from these groups to apply for the position. The University of Pittsburgh is an affirmative action/equal opportunity employer and does not discriminate on the basis of age, color, disability, gender, gender identity, marital status, national or ethnic origin, race, religion, sexual orientation, or veteran status.

Zervantonakis Laboratory

Kozai Co-Chairs 2020 Gordon Research Conference to Foster Collaborations in Neural Engineering

Bioengineering

PITTSBURGH (Feb. 20, 2020) … Neuroelectronic interfaces are the foundation of technology that connects the human mind to machine and helps to restore motor and sensory function to individuals with neurological diseases and disorders. This technology has been introduced as a successful treatment to the clinical environment, but issues with device stability and longevity remain. The 2020 Gordon Research Conference (GRC) on Neuroelectronic Interfaces will bring together a multidisciplinary group of scientists and engineers to address challenges in this area and collectively discuss how to drive innovation for next-generation devices. Takashi D-Y Kozai, assistant professor of bioengineering at the University of Pittsburgh, will co-chair the event in Ventura, California, March 15-20, 2020. “The challenges with this technology have been long-standing and complex to solve. It requires fundamentally understanding the problem from both biological and engineering perspectives,”  said Kozai, who helms the Bio-Integrating Optoelectric Neural Interface Cybernetics Lab in the Swanson School of Engineering. “Therefore, the goal of this GRC is to bring together fundamental neuroscientists, brain neurophysiologists, brain biocompatibility experts, material scientists, electrical engineers, clinical neural engineers, and clinical scientists to really understand what the fundamental problems and needs are for these neural interface technologies. “The Gordon Research Conference format is conducive to this type of problem solving and innovation as it brings experts together for a week in an intimate setting,” he continued. “This conference has seeded many new collaborations and new directions in neural engineering.” Pitt is no stranger to multidisciplinary research in this area, and this year’s GRC on Neuroelectronic Interfaces will feature presentations from five professors, each representing different departments at the University: Robert Gaunt (Physical Medicine and Rehabilitation Sciences) "Bidirectional Brain Computer Interfaces: Science and Function" Douglas Weber (Bioengineering) "Recording and Stimulating Sensory Neurons in Dorsal Root Ganglia and Spinal Cord" Elizabeth Tyler-Kabara (Neurological Surgery) "Longevity of Intracranial Recordings for BCI" Franca Cambi (Neurology) "The Role of Myelin and Oligodendrocytes in Neural Function and Repair: Implications for Recording Devices" Alberto Vazquez (Radiology) "Optogenetic Assessment of the Contribution of Neuronal Populations to Tissue Metabolic Load and Blood Flow Regulation: Vulnerable Neuronal Populations to Brain Injury" In the past year, Swanson School faculty have received notable awards in this field of research: Kozai received $1,600,000 from the National Institutes of Health (NIH) to develop an innovative wireless neural device for long-term and precise stimulation; and Xinyan Tracy Cui, professor of bioengineering, developed a coating that improves the performance of microelectrode array technology and was awarded a $2,370,218 NIH grant. Douglas Weber, associate professor of bioengineering, and his colleagues in the Rehab Neural Engineering Labs will collaborate on a $20,000,000 Defense Advanced Research Projects Agency (DARPA) grant to develop non-invasive wearable technologies for able-bodied individuals. “We’ve received tremendous support for this conference from the University of Pittsburgh, as well as our industry and foundation partners,” said Kozai. “The level and number of sponsoring partners highlight how important these collaborations are in achieving high-quality work and realizing the full potential of this pioneering and life-changing technology. The leadership at Pitt has cultivated an environment for excellent multidisciplinary research collaborations.” This GRC will be held in conjunction with the "Neuroelectronic Interfaces (GRS): Creating a Roadmap to Translating Neural Technologies" Gordon Research Seminar (GRS). # # #

Bryan Brown Featured in the Products of Pittsburgh Podcast

Bioengineering

This story is reposted from the Clinical & Translational Science Institute. Click here to view the original post. The Products of Pittsburgh podcast is about the people in Pittsburgh – innovators, scientists, community leaders – and the remarkable stories behind how they came to be and the work they have produced. In 2001, Bryan Brown came to Pittsburgh to study mechanical engineering at the University of Pittsburgh where he would go on to obtain his PhD in bioengineering and become a faculty member at the university.    From winning multiple awards to co-founding a company, Bryan is well on his way to making an impact on health care innovation. About BrownBryan Brown, PhD is an Associate Professor of Bioengineering with secondary appointments in Obstetrics, Gynecology, and Reproductive Sciences as well as Clinical and Translational Sciences at the University of Pittsburgh.  He’s a core faculty member of the McGowan Institute for Regenerative Medicine where he serves as Director of Educational Outreach. He is a two time Pitt Innovation Challenge awardee and serves as Chief Technology Officer of Renerva, LLC, a Pitt start-up company that he co-founded.  Brown received both his B.S. and PhD from the University of Pittsburgh.

Got Slime? Using Regenerative Biology to Restore Mucus Production

Bioengineering

PITTSBURGH (Jan. 31, 2020) … Let’s talk about slime. Mucus is a protective, slimy secretion produced by goblet cells and which lines organs of the respiratory, digestive, and reproductive systems. Slime production is essential to health, and an imbalance can be life-threatening. Patients with diseases such as asthma, chronic obstructive pulmonary disease (COPD), and ulcerative colitis produce too much mucus, often after growing too many goblet cells. Loss of goblet cells can be equally devastating - for instance during cancer, after infection, or injury. The balance of slime creation, amount, and transport is critical, so doctors and medical researchers have long sought the origins of goblet cells and have been eager to control processes that regenerate them and maintain balanced populations. Recently, a group of bioengineers at the University of Pittsburgh discovered a case of goblet cell regeneration that is both easily accessible and happens incredibly fast on cells isolated from early developing frog embryos. Their findings were published this week in the journal Nature Communications (DOI: 10.1038/s41467-020-14385-y). Lance Davidson, William Kepler Whiteford Professor of Bioengineering at Pitt, leads the MechMorpho Lab in the Swanson School of Engineering where his researchers study the role of mechanics in human cells as well as the Xenopus embryo - an aquatic frog native to South Africa. “The Xenopus tadpole, like many frogs, has a respiratory skin that can exchange oxygen and perform tasks similar to a human lung,” explained Davidson. “Like the human lung, the surface of the Xenopus respiratory skin is a mucociliated epithelium, which is a tissue formed from goblet cells and ciliated cells that also protects the larva against pathogens. Because of these evolutionary similarities, our group uses frog embryonic organoids to examine how tissue mechanics impact cell growth and tissue formation.” Studying this species is a rapid and cost-effective way to explore the genetic origins of biomechanics and how mechanical cues are sensed, not just in the frog embryo, but universally. When clinicians study cancer in patients, such changes can take weeks, months, or even years, but in a frog embryo, changes happen within hours. “In this project, we took a group of mesenchymal cells out of the early embryo and formed them into a spherical aggregate, and within five hours, they began to change,” Davidson said. “These cells are known to differentiate into a variety of types, but in this scenario, we discovered that they changed very dramatically into a type of cell that they would not have changed into had they been in the embryo.” The lab surprisingly uncovered a case of regeneration that restores a mucociliated epithelium from mesenchymal cells. They performed the experiment multiple times to confirm the unexpected findings and began to look closely at what microenvironmental cues could drive cells into an entirely new type. “We have tools to modulate the mechanical microenvironment that houses the cells, and to our surprise, we found that if we made the environment stiffer, the aggregates changed into these epithelial cells,” explained Davidson. “If we made it softer, we were able to block them from changing. This finding shows that mechanics alone can cause important changes in the cells, and that is a remarkable thing.” Davidson’s group is interested in how cells, influenced by mechanics, may affect disease states. The results detailed in this article may drive new questions in cancer biology, prompting researchers to consider whether certain kinds of invasive cancer cells might revert to a resting cell type based on the stiffness or softness of their surroundings. “When applying these results to cancer biology, one might ask, ‘If tumors are surrounded by soft tissues, would they become dormant and basically non-invasive?’ Or, ‘If you have them in stiff tissues, would they invade and become deadly?’” said Davidson. “These are major questions in the field that biomechanics may be able to help answer. Many researchers focus solely on the chemical pathways, but we are also finding mechanical influencers of disease.” Hye Young Kim, a young scientist fellow at Institute for Basic Science (IBS) and former member of the MechMorpho Lab, will continue this work at the Center for Vascular Research located at Korea Advanced Institute of Science and Technology (KAIST). She will study how cell motility changes during regeneration and how epithelial cells assemble a new epithelium. Davidson and his lab will explore how this novel case of mechanical cues are sensed by mesenchymal cells and how these mechanical induction pathways are integrated with known pathways that control cell fate choices. "Frog embryos and organoids give us unparalleled access to study these processes, far more access than is possible with human organs,” he said. “The old ideas that regeneration is controlled exclusively by diffusing growth factors and hormones is giving way to the recognition that the physical mechanics of the environment – such as how rubbery or fluid the environment -  play just as critical a role." ### This research was supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Image caption: "Green Slime covers the surface of a tadpole (bottom) and a goblet-cell regenerated aggregate (top, not the same scale). The images show the molecule intelectin-1, an important factor in tadpole skin, and one of the slime factors synthesized and secreted by goblet cells (single goblet cells can be seen in the aggregate). In human lung, intelectin-1 binds bacteria and is on the front line of the innate immune system. Images courtesy of Hye Young Kim and Lance Davidson."

Impacting human life now

Bioengineering, Student Profiles

Reposted with permission from the University of Pittsburgh Center for Research Computing. Click here to read the original story. Two images of MRI brain scans are displayed side-by-side on a poster in the Radiofrequency Research Facility in the basement of BST 3, one image marked 3T and one 7T. On the 7T image the hippocampus region of the brain displays a tracing of vessels not visible on the 3T image. “You can clearly see a microstructure in the 7T scan that doesn’t appear in the 3T scan,”  post-doc Tales Santini points out. “That kind of detail is what our scanner system offers.” That scanner is one of the most powerful MRI devices in the world – designated 7T  for 7 Tesla, a measure of the strength of an electromagnetic field (by comparison, Earth’s magnetic field is about 0.00065 T and a refrigerator magnet 0.01 T). MRI scanners in use are primarily 1.5 and 3 Tesla. The increased power of the 7 Tesla scanner reveals details not visible in typical MRI machines. With a resolution up to 180 microns – a micron is a millionth of a meter – the 7 Tesla can identify problems much earlier than existing scanners. 7 Tesla is particularly effective in early detection of brain issues implicated in diseases associated with aging, such as Alzheimer’s and late life depression, diseases which are a focus of the Radiofrequency Research Facility and the 7 Tesla Bioengineering Research program, directed by Tamer Ibrahim, professor of bioengineering, radiology, and psychiatry. The increased frequency of the 7 Tesla represents challenges. If the electromagnetic waves do not enter the skull evenly in a uniform pattern, heat concentrates in individual areas of the brain, considerably raising their temperatures. The maximum possible heating allowed by the U.S.. Food and Drug Administration is one degree centigrade. The lab is currently developing technology to smooth those electromagnetic waves using an array of 70 intricate radiofrequency antennas surrounding the head and neck, dubbed the Tic-Tac-Toe antenna owing to a nine-square grid marked with X’s and O’s displayed on the array’s housing. The team uses the Center for Research Computing to simulate hundreds of thousands of possible configurations of the antennas to create the most uniform possible waves. “The wavelength of tissue is short, about 12 centimeters at 7 Tesla, while the human head is electrically large, about 20 cm front to back,” explains Ibrahim. “We must create a relatively homogenous magnetic field to image a head that is about twice the wavelength of the 7 Tesla in tissue. This is extremely challenging. Without a uniform field, the image quality and usefulness will significantly degrade, and the electrical field can localize and heat the tissue.” Engineer Anthony Defranco, Tamer Ibrahim, and post-doc Tales Santini. Santini is holding the housing of the Tic-Tac-Toe antenna. Now the computational problem. Hundreds of thousands of configurations of the Tic-Tac-Toe antennas must be modeled to optimize that balance of uniform imaging while minimizing the danger of heating before any testing. Each of the 70 antennas is simulated in the presence of the other 69 antennas, the electromagnetic fields from these simulations are combined – potentially in hundreds of millions of different ways - to form the most even, yet safe, magnetic field distribution.  “We use CRC to do the simulation and optimization of the coils, but also in processing human imaging data,” Santini explained. The 7 Tesla scanner and Tic-Tac-Toe antennas are being heavily used in clinical studies. Ibrahim estimates that his team of 12 PhD students, several MS and BS students, two engineering staff, and two post-docs has performed 4,000 human head and neck scans between 2017 and 2024 looking at blood flow, cerebral spinal fluid, small vessels and microstructures in the hippocampus and other brain regions, all of which correlate with diseases like Alzheimer’s. The research is not limited to conditions associated with aging but includes major depressive disorder, schizophrenia, sickle cell, mild cognitive impairment, normal aging, late-life depression, dementia, psychosis, neurocognitive disparities, and linking personality to health, among others. The Tic-Tac-Toe radiofrequency coil system has achieved breakthrough results in terms of image quality and consistency at 7 Tesla. The new capabilities are stimulating significant translational and collaborative research.  Through extensive collaborations with the Alzheimer Disease Research Center and the  Pitt departments of Psychiatry, Medicine, Epidemiology, Neurology, Psychology, and Anesthesiology, Ibrahim’s lab has attracted close to $40 million in grant funding over the last four years, including 17 National Institutes of Health grants. A recent NIH award of over $3.75 million funds research by Ibrahim and collaborators in the Department of Psychiatry into developing new 7 Tesla technology to investigate relationships between preclinical Alzheimer’s disease and small vessel and cerebrospinal fluid conditions. Ibrahim is also central to an initiative of the departments of Bioengineering and Psychiatry to create a multidisciplinary training program for pre-doc bioengineering students to participate in mental health research, an initiative that recently received $1.1 million from the NIH. “This is an exciting time,” says Ibrahim. “Our engineering innovations are being used on real patient studies. We’re not making something that just could be used some time in the future. We are impacting human life now.”

Take heart: Pitt study reveals how relaxin targets cardiovascular disease

Bioengineering, Student Profiles

PITTSBURGH (Jan. 6, 2020) … As a healthy heart ages, it becomes more susceptible to cardiovascular diseases. Though researchers have discovered that relaxin, an insulin-like hormone, suppresses atrial fibrillation (AF), inflammation, and fibrosis in aged rats, the underlying mechanisms of these benefits are still unknown. In a recent Scientific Reports paper, University of Pittsburgh graduate student Brian Martin discusses how relaxin interacts with the body’s signaling processes to produce a fundamental mechanism that may have great therapeutic potential. The study, “Relaxin reverses maladaptive remodeling of the aged heart through Wnt-signaling” (DOI: 10.1038/s41598-019-53867-y) was led by Guy Salama, professor of medicine at Pitt, and Brian Martin, a graduate student researcher from the Swanson School of Engineering’s Department of Bioengineering. “Relaxin is a reproductive hormone discovered in the early 20th century that has been shown to suppress cardiovascular disease symptoms,” said Martin. “In this paper, we show that relaxin treatment reverses electrical remodeling in animal models by activating canonical Wnt signaling - a discovery that reveals a fundamental underlying mechanism behind relaxin’s benefits.” A better understanding of how relaxin interacts with the body may improve its efficacy as a therapy to treat cardiovascular disease in humans. As the U.S. population ages, the rates of these age-associated diseases are expected to rise, requiring better treatment for this leading cause of death. According to a report from the American Heart Association, the total direct medical costs of cardiovascular disease are projected to increase to $749 billion in 2035. “A common problem in age-associated cardiovascular disease is altered electrical signaling required for proper heart contraction,” Martin explained. “When ions in the heart and their associated channels to enter or exit the heart are disrupted, complications occur.” “Natural, healthy aging has been shown to be accompanied by changes in structure and function,” Salama added. “For example, aged cardiomyocytes start to express embryonic contractile proteins and fewer voltage-gated Na+ channels by unknown mechanisms. The reversal of some aspects of the aging process by relaxin is mediated by the reactivation of Wnt canonical signaling which may partly explain mechanisms of the aging process.” The group’s study found that relaxin upregulated the prominent sodium channel, Nav1.5, in cells of heart tissue via a mechanism inhibited by the Wnt pathway inhibitor Dickkopf-1. “Wnt signaling is thought to be active primarily in the developing heart and inactive later in life,” Martin said. “However, we show that relaxin can reactivate Wnt signaling in a beneficial way to increase Nav1.5.” Increased Nav1.5 is associated with better electrical signaling in the heart may reduce susceptibility to cardiac rhythm disorders. “Further, we show that relaxin can also reverse the age-associated reduction in cell adhesion molecules and cell-cell communication proteins,” he continued. “In summary, relaxin appears to reverse problematic reductions or pathological reorganization of vital cardiac signaling proteins.” While these data provide new insight into relaxin’s mechanisms of action, further work is needed to understand the precise steps required for relaxin to alter Wnt signaling and if steps can be taken to directly alter Wnt signaling to provide its beneficial effects. ### Image caption: “Left ventricular tissue sections (7-µm thick) from aged rat hearts (24 months old) were labeled with the nuclear stain (DAPI-blue) and an antibody against β-catenin (green). Rats were treated with Relaxin (0.4 mg/kg/day for 2-weeks) (left panel) or with the control vehicle (sodium acetate) (right panel) and the tissue sections were imaged by confocal microscopy (600X magnification). Relaxin treatment (left) produced a marked positive remodeling of aged ventricles with a reduction of cell hypertrophy, improved organization of myofibrils and cell membrane compared to untreated, control aged hearts (right).” Credit: Dr. Guillermo Romero.