Assistant Professor

Adjunct Professor
The College of William & Mary
Department of Applied Science

Lewis Hall, #3047
Office: (757) 446-7191
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Biomedical Sciences Program Track: Molecular Integrative Biosciences (MIB)

Education

• B.A., Washington University, St. Louis
• M.S., Johns Hopkins University
• Ph.D., Johns Hopkins School of Medicine
• Postdoctoral Training, Yale University

Research Interests

Cancer is marked by uncontrolled proliferation and inappropriate survival of damaged cells in the body. Many processes used to direct the proper growth, differentiation and cell death of tissues in the developing embryo are identical to the genetic pathways that are perturbed in the cancerous state. Recently, an abundant class of non-coding RNAs, microRNAs (miRNAs), has been implicated to function as tumor suppressor genes and oncogenes and is often dysregulated in human cancers. Little is known regarding how these molecules contribute to cellular transformation and tumor formation. MiRNAs are small ~22 nucleotide single-stranded RNAs that negatively regulate expression of their gene targets. Animal miRNAs bind to complementary sequences located in the 3’ untranslated region (3’ UTR) of their target protein-coding messenger RNAs (mRNAs), resulting in translational inhibition and/or mRNA degradation.

Dr. Kerscher is very interested in studying the role miRNAs play in controlling developmental events and how this relates to cancer progression. The lab employs the simple roundworm, Caenorhabditis elegans, an organism easily grown and studied in the laboratory and amenable to genetic manipulation, to characterize the biological function of novel miRNA genes. Specifically, the lab focuses on the lin-4 and let-7 miRNA families, which they have found to direct important developmental processes such as cell-fate specification and gonad formation. The lin-4 and let-7 miRNAs are highly conserved across animal phylae and provide a unique opportunity to apply knowledge gained in the nematode to elucidate the mechanisms of human disease.

The lab is currently investigating whether the function of certain miRNAs and their targets are also conserved and control similar proliferation and cancer-associated pathways in mammals using both mouse models and human cell culture systems. For instance, Dr. Kerscher and colleagues recently showed that administration of the let-7 miRNA reduces tumor formation in a lung cancer mouse model, supporting the notion that this miRNA family has a tumor suppressor role in this tissue.

The Kerscher Lab is also investigating the role of the lin-4 and let-7 miRNA families outside of the lung, and has extended their findings to oncogenic pathways involved in urothelial cancers. To this end, the lab in collaboration with the Virginia Prostate Center is identifying potential miRNA biomarkers for the detection of human bladder and prostate cancers. Dr. Kerscher’s research focus on miRNAs holds great potential for the discovery of new diagnostic and therapeutic avenues for the treatment of cancer.

Selected Publications

• Weidhaas, J.B.*, Esquela-Kerscher, A.*, Ratner, E., Slack, F.J. MicroRNA Detection and Profiling. Book chapter in Methods in Molecular Biology. The Humana Press Inc. In press. (*These authors contributed equally to this work.)
• Esquela-Kerscher, A, Trang, P, Wiggins, J.F., Patrawala, L., Cheng, A., Ford, L., Weidhaas, J.B., Brown, D., Bader, A.G., Slack, F.J. (2008). The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle March 3; 7(6).
• Johnson, C.D.*, Esquela-Kerscher, A.*, Stefani, G.*, Byrom, M., Kelnar, K., Ovcharenko, D., Wilson, M., Wang, X., Shelton, J., Shingara, J., Chin, L., Brown, D., Slack, F.J. (2007). The let-7 MicroRNA Represses Cell Proliferation Pathways in Human Cells. Cancer Res 15; 67(16):7713-22. (*These authors contributed equally to this work.)
• Esquela-Kerscher, A., and Slack, F.J. (2006). Oncomirs – MicroRNAs with a role in cancer. Nature Reviews Cancer 6, 259-269. (Featured cover article)
• Esquela-Kerscher, A., Johnson, S.M., Bai, L., Saito, K., Partridge, J., Reinert, K., and Slack, F.J. (2005). Post-embryonic expression of C. elegans microRNAs belonging to the lin-4 and let-7 families in the hypodermis and reproductive system. Dev Dyn 234, 868-877.
• Schulman, B., Esquela-Kerscher, A., Slack, F.J. (2005). Temporal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis. Dev Dyn 234, 1046-1054.
• Zimmers, T.A., Jin, X., Hsiao, E.C., McGrath, S.A., Esquela, A.F., Koniaris, L.G (2005). Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock 23(6), 543-548.
• Esquela-Kerscher, A., and Slack, F.J. (2004). News and Views: The age of high-throughput microRNA profiling. Nature Meth 1, 106-107.
• Esquela, A.F. and Lee, S.-J. (2003). Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol 257, 356-370. (Esquela, A.F. - corresponding author)
• Zimmers, T.A., Davies, M.V., Koniaris, L.G., Haynes, P., Esquela, A.F., Tomkinson, K.N., McPherron, A.C., Wolfman, N.M., and Lee S.-J. (2002). Induction of cachexia in mice by systemically administered myostatin. Science 296, 1486-1488.

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