headshot of Amanda Clark

Amanda Clark

Research Assistant Professor
AMC235@pitt.edu
Bioengineering Department

overview

The Clark lab focuses on determining the molecular and cellular regulators of metastatic dormancy and recurrence within the liver. We utilize a novel all-human ex vivo 3D liver microphysiological system to model metastasis. The system has not only enabled the recreation of dormant-emergent metastatic cancer progression as observed in vivo but also the identification of mechanisms, candidate biomarkers, and new therapeutic opportunities to target the various stages of metastasis. Our current research centers on examining how intercellular crosstalk mediated by extracellular vesicles regulates metastatic breast cancer dormancy in the liver.

about

PhD, Griffith University, 2009 - 2013

Honours, Griffith University, 2007 - 2008

Bachelor of Biomedical Science, Griffith University, 2004 - 2006

Dai, B., Clark, A.M., & Wells, A. (2024). Mesenchymal Stem Cell-Secreted Exosomes and Soluble Signals Regulate Breast Cancer Metastatic Dormancy: Current Progress and Future Outlook. Int J Mol Sci, 25(13), 7133.MDPI. doi: 10.3390/ijms25137133.

McDonald, J.C., & Clark, A.M. (2024). Modeling Tumor Cell Dormancy in an Ex Vivo Liver Metastatic Niche. Methods Mol Biol, 2811, 37-53.Springer Nature. doi: 10.1007/978-1-0716-3882-8_3.

Korentzelos, D., Wells, A., & Clark, A.M. (2022). Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer. Sci Rep, 12(1), 6657.Springer Nature. doi: 10.1038/s41598-022-10724-9.

Clark, A.M. (2021). Modeling the Complexity of the Metastatic Niche Ex Vivo. Methods Mol Biol, 2258, 221-239.Springer Nature. doi: 10.1007/978-1-0716-1174-6_15.

Clark, A.M., Allbritton, N.L., & Wells, A. (2021). Integrative microphysiological tissue systems of cancer metastasis to the liver. Semin Cancer Biol, 71, 157-169.Elsevier. doi: 10.1016/j.semcancer.2020.06.010.

Clark, A.M., Heusey, H.L., Griffith, L.G., Lauffenburger, D.A., & Wells, A. (2021). IP-10 (CXCL10) Can Trigger Emergence of Dormant Breast Cancer Cells in a Metastatic Liver Microenvironment. Front Oncol, 11, 676135.Frontiers. doi: 10.3389/fonc.2021.676135.

Clark, A.M., Magawa, C., Pliego-Zamora, A., Low, P., Reynolds, M., & Ralph, S.J. (2021). Tea tree oil extract causes mitochondrial superoxide production and apoptosis as an anticancer agent, promoting tumor infiltrating neutrophils cytotoxic for breast cancer to induce tumor regression. Biomed Pharmacother, 140, 111790.Elsevier. doi: 10.1016/j.biopha.2021.111790.

Marti, J.L.G., Beckwitt, C.H., Clark, A.M., & Wells, A. (2021). Atorvastatin facilitates chemotherapy effects in metastatic triple-negative breast cancer. Br J Cancer, 125(9), 1285-1298.Springer Nature. doi: 10.1038/s41416-021-01529-0.

Korentzelos, D., Clark, A.M., & Wells, A. (2020). A Perspective on Therapeutic Pan-Resistance in Metastatic Cancer. Int J Mol Sci, 21(19), 7304.MDPI. doi: 10.3390/ijms21197304.

Ma, B., Wells, A., & Clark, A.M. (2020). The pan-therapeutic resistance of disseminated tumor cells: Role of phenotypic plasticity and the metastatic microenvironment. Semin Cancer Biol, 60, 138-147.Elsevier. doi: 10.1016/j.semcancer.2019.07.021.

Jiang, Y., Wells, A., Sylakowski, K., Clark, A.M., & Ma, B. (2019). Adult Stem Cell Functioning in the Tumor Micro-Environment. Int J Mol Sci, 20(10), 2566.MDPI. doi: 10.3390/ijms20102566.

Beckwitt, C.H., Clark, A.M., Ma, B., Whaley, D., Oltvai, Z.N., & Wells, A. (2018). Statins attenuate outgrowth of breast cancer metastases. Br J Cancer, 119(9), 1094-1105.Springer Nature. doi: 10.1038/s41416-018-0267-7.

Beckwitt, C.H., Clark, A.M., Wheeler, S., Taylor, D.L., Stolz, D.B., Griffith, L., & Wells, A. (2018). Liver 'organ on a chip'. Exp Cell Res, 363(1), 15-25.Elsevier. doi: 10.1016/j.yexcr.2017.12.023.

Clark, A.M., Kumar, M.P., Wheeler, S.E., Young, C.L., Venkataramanan, R., Stolz, D.B., Griffith, L.G., Lauffenburger, D.A., & Wells, A. (2018). A Model of Dormant-Emergent Metastatic Breast Cancer Progression Enabling Exploration of Biomarker Signatures. Mol Cell Proteomics, 17(4), 619-630.Elsevier. doi: 10.1074/mcp.RA117.000370.

Khazali, A.S., Clark, A.M., & Wells, A. (2018). Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy. Br J Cancer, 118(4), 566-576.Springer Nature. doi: 10.1038/bjc.2017.414.

Wells, A., Clark, A., Bradshaw, A., Ma, B., & Edington, H. (2018). The great escape: How metastases of melanoma, and other carcinomas, avoid elimination. Exp Biol Med (Maywood), 243(17-18), 1245-1255.Frontiers. doi: 10.1177/1535370218820287.

Dioufa, N., Clark, A.M., Ma, B., Beckwitt, C.H., & Wells, A. (2017). Bi-directional exosome-driven intercommunication between the hepatic niche and cancer cells. Mol Cancer, 16(1), 172.Springer Nature. doi: 10.1186/s12943-017-0740-6.

Khazali, A.S., Clark, A.M., & Wells, A. (2017). A Pathway to Personalizing Therapy for Metastases Using Liver-on-a-Chip Platforms. Stem Cell Rev Rep, 13(3), 364-380.Springer Nature. doi: 10.1007/s12015-017-9735-3.

Clark, A.M., Ma, B., Taylor, D.L., Griffith, L., & Wells, A. (2016). Liver metastases: Microenvironments and ex-vivo models. Exp Biol Med (Maywood), 241(15), 1639-1652.Frontiers. doi: 10.1177/1535370216658144.

Clark, A.M., Wheeler, S.E., Young, C.L., Stockdale, L., Shepard Neiman, J., Zhao, W., Stolz, D.B., Venkataramanan, R., Lauffenburger, D., Griffith, L., & Wells, A. (2016). A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties. Lab Chip, 17(1), 156-168.Royal Society of Chemistry (RSC). doi: 10.1039/c6lc01171c.

Ma, B., Wheeler, S.E., Clark, A.M., Whaley, D.L., Yang, M., & Wells, A. (2016). Liver protects metastatic prostate cancer from induced death by activating E-cadherin signaling. Hepatology, 64(5), 1725-1742.Wolters Kluwer. doi: 10.1002/hep.28755.

Yang, M., Ma, B., Shao, H., Clark, A.M., & Wells, A. (2016). Macrophage phenotypic subtypes diametrically regulate epithelial-mesenchymal plasticity in breast cancer cells. BMC Cancer, 16(1), 419.Springer Nature. doi: 10.1186/s12885-016-2411-1.

Clark, A.M., Wheeler, S.E., Taylor, D.P., Young, C.L., Pillai, V.C., Stolz, D.B., Venkataramanan, R., Lauffenburger, D.A., Griffith, L.G., & Wells, A. (2015). Modeling breast cancer dormancy and re-emergence. CANCER RESEARCH, 75(9_Supplement), p1-07-01-p1-07-01.American Association for Cancer Research (AACR). doi: 10.1158/1538-7445.SABCS14-P1-07-01.

Furukawa, M., Wheeler, S., Clark, A.M., & Wells, A. (2015). Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells. In Samant, R. (Ed.). PLoS One, 10(1), e0118060.Public Library of Science (PLoS). doi: 10.1371/journal.pone.0118060.

Low, P., Clark, A.M., Chou, T.C., Chang, T.C., Reynolds, M., & Ralph, S.J. (2015). Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): inhibition of LPS-induced NF-κB activation and cytokine production in myeloid cell lines. Int Immunopharmacol, 26(1), 257-264.Elsevier. doi: 10.1016/j.intimp.2015.03.034.

Clark, A.M., Wheeler, S.E., Taylor, D.P., Pillai, V.C., Young, C.L., Prantil-Baun, R., Nguyen, T., Stolz, D.B., Borenstein, J.T., Lauffenburger, D.A., Venkataramanan, R., Griffith, L.G., & Wells, A. (2014). A microphysiological system model of therapy for liver micrometastases. Exp Biol Med (Maywood), 239(9), 1170-1179.Frontiers. doi: 10.1177/1535370214532596.

Taylor, D.P., Clark, A., Wheeler, S., & Wells, A. (2014). Hepatic nonparenchymal cells drive metastatic breast cancer outgrowth and partial epithelial to mesenchymal transition. Breast Cancer Res Treat, 144(3), 551-560.Springer Nature. doi: 10.1007/s10549-014-2875-0.

Wheeler, S.E., Clark, A.M., Taylor, D.P., Young, C.L., Pillai, V.C., Stolz, D.B., Venkataramanan, R., Lauffenburger, D., Griffith, L., & Wells, A. (2014). Spontaneous dormancy of metastatic breast cancer cells in an all human liver microphysiologic system. Br J Cancer, 111(12), 2342-2350.Springer Nature. doi: 10.1038/bjc.2014.533.

Horton, R.E., Grant, G.D., Matthews, B., Batzloff, M., Owen, S.J., Kyan, S., Flegg, C.P., Clark, A.M., Ulett, G.C., Morrison, N., Peak, I.R., & Beacham, I.R. (2013). Quorum sensing negatively regulates multinucleate cell formation during intracellular growth of Burkholderia pseudomallei in macrophage-like cells. In II, R.M.R. (Ed.). PLoS One, 8(5), e63394.Public Library of Science (PLoS). doi: 10.1371/journal.pone.0063394.

Wheeler, S.E., Borenstein, J.T., Clark, A.M., Ebrahimkhani, M.R., Fox, I.J., Griffith, L., Inman, W., Lauffenburger, D., Nguyen, T., Pillai, V.C., Prantil-Baun, R., Stolz, D.B., Taylor, D., Ulrich, T., Venkataramanan, R., Wells, A., & Young, C. (2013). All-human microphysical model of metastasis therapy. Stem Cell Res Ther, 4 Suppl 1(Suppl 1), S11.Springer Nature. doi: 10.1186/scrt372.

Ito, K., Stannard, K., Gabutero, E., Clark, A.M., Neo, S.Y., Onturk, S., Blanchard, H., & Ralph, S.J. (2012). Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment. Cancer Metastasis Rev, 31(3-4), 763-778.Springer Nature. doi: 10.1007/s10555-012-9388-2.

Oesterreich, S., Miller, L., Rosenzweig, M.Q., Bartholow, T.L., Yates, M., Elangovan, A., Savariau, L., Casey, A.N., Priedigkeit, N., Ding, K., Wedn, A., Bin Liu, J., Brown, D.D., Hyder, T., Pecar, G., Carleton, N., Bittar, H.T., Geisler, D., Lopez-Nunez, O., Clark, A.M., Wells, A., Roy, P., Puhalla, S., Howard, N., Needles, C., Trent, S., Walker, S., Hodgdon, C., Bhargava, R., Atkinson, J.M., & Lee, A.V. (2023). Hope for OTHERS - An organ donation program for metastatic breast cancer research. In CANCER RESEARCH, 83(5), (p. p6-14-02-p6-14-02).American Association for Cancer Research (AACR). doi: 10.1158/1538-7445.SABCS22-P6-14-02.

Beckwitt, C.H., Clark, A.M., Warita, K., Oltvai, Z.N., & Wells, A. (2018). Adjuvant statin therapy efficacy is dictated by tumor dormancy and statin lipophilicity in ex vivo and in vivo models of metastatic breast cancer. In CANCER RESEARCH, 78(4).

Beckwitt, C.H., Clark, A.M., Warita, K., Oltvai, Z.N., & Wells, A. (2017). Adjuvant Statin Therapy Efficacy is Dictated by Tumor Dormancy and Statin Lipophilicity in Ex Vivo and In Vivo Models of Metastatic Breast Cancer. In FASEB JOURNAL, 31.

Clark, A.M., Dioufa, N., Chan, K., Edington, C.D., Kumar, M., Wheeler, S.E., Venkataramanan, R., Stolz, D.B., Trumper, D., Griffith, L., Lauffenburger, D., & Wells, A. (2017). A Multi-Organ Microphysiological System that Models Dormant-Emergent Metastatic Breast Cancer Progression. In AMERICAN JOURNAL OF PATHOLOGY, 187(10), (p. 2356).

Clark, A.M., Wheeler, S.E., Young, C.L., Neiman, J.S., Pillai, V., Stockdale, L., Stolz, D., Lauffenburger, D.A., Venkataramanan, R., Griffith, L.G., & Wells, A. (2017). Mechanical properties of matrices strongly influence spontaneous tumor dormancy and responses to chemotherapy in a 3D model of metastasis. In CANCER RESEARCH, 77(2_Supplement), (p. a01).American Association for Cancer Research (AACR). doi: 10.1158/1538-7445.EPSO16-A01.

Edington, C.D., Cirit, M., Chen, W.L.K., Clark, A.M., Wells, A., Trumper, D.L., & Griffith, L.G. (2017). Integration of systems biology with organs-on-chips to humanize therapeutic development. In Gray, B.L., & Becker, H. (Eds.). In Proceedings of SPIE--the International Society for Optical Engineering, 10061, (p. 1006113-1006113-9).SPIE, the international society for optics and photonics. doi: 10.1117/12.2256078.

Beckwitt, C., Wheeler, S.E., Clark, A.M., Pillai, V.C., Young, C.L., Stolz, D.B., Lauffenburger, D.A., Venkataramanan, R., Griffith, L.G., & Wells, A. (2016). Breast cancer dormancy, re-emergence, and treatment. In CANCER RESEARCH, 76(4_Supplement), (p. p2-05-19-p2-05-19).American Association for Cancer Research (AACR). doi: 10.1158/1538-7445.SABCS15-P2-05-19.

Clark, A.M., Wheeler, S.E., Young, C.L., Pillai, V.C., Stolz, D.B., Lauffenburger, D.A., Venkataramanan, R., Griffith, L.G., & Wells, A. (2016). Elucidating candidate biomarkers of breast cancer progression and dormancy using a 3D model of metastasis. In CANCER RESEARCH, 76(7_Supplement), (p. a41).American Association for Cancer Research (AACR). doi: 10.1158/1538-7445.TUMMET15-A41.

Clark, A.M., Wheeler, S.E., Young, C.L., Pillai, V.C., Stolz, D.B., Lauffenburger, D.A., Venkataramanan, R., Griffith, L.G., & Wells, A. (2016). Elucidating candidate biomarkers of breast cancer progression and dormancy using a 3D model of metastasis. In CANCER RESEARCH, 76(7_Supplement), (p. pr11).American Association for Cancer Research (AACR). doi: 10.1158/1538-7445.TUMMET15-PR11.

Khazali, A.S., Clark, A., Wheeler, S., & Wells, A. (2016). Breast Cancer Emergence from Dormancy can be Activated by Hepatic Stellate Cells. In FASEB JOURNAL, 30.

Nguyen, T.V., Kim, E.S., Coppeta, J.R., Wheeler, S.E., Clark, A.M., Lever, A.R., Cirit, M., Yu, J., Spencer, A.J., Sinatra, F.L., Prantil-Baun, R., Wells, A., Griffith, L.G., & Borenstein, J.T. (2014). Automated reagent delivery, media replenishment, and media sampling platform for open cell culture systems. In 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014, (pp. 491-493).

Wheeler, S.E., Taylor, D.P., Clark, A.M., Borenstein, J.T., Ebrahimkhani, M.R., Inman, W., Nguyen, T., Pillai, V.C., Prantil-Baun, R., Ulrich, T.A., Venkataramanan, R., Lauffenburger, D.A., Griffith, L., Stolz, D.B., & Wells, A. (2013). Modeling breast cancer dormancy. In CANCER RESEARCH, 73(24_Supplement), (p. p5-04-08-p5-04-08).American Association for Cancer Research (AACR). doi: 10.1158/0008-5472.SABCS13-P5-04-08.