Associate Professor of Cancer Biology
Department of Microbiology and Molecular Cell Biology
Leroy T. Canoles Jr. Cancer Research Center
Harry T. Lester Hall 421
651 Colley Avenue
Norfolk, Virginia 23501
Office: (757) 446-7191
- Biomedical Sciences Program Track: Molecular Integrative Biosciences (MIB)
- B.A. - Washington University in St Louis
- M.S. - Johns Hopkins University
- Ph.D. - Johns Hopkins School of Medicine
- Postdoctoral Fellow - Yale University
- Assistant Professor
Eastern Virginia Medical School
Department of Microbiology & Molecular Cell Biology
- Adjunct Assistant Professor
College of William & Mary
Department of Applied Science
Lab People and Photos
Lab folks having lunch in Ghent.
Cancer is marked by uncontrolled proliferation and inappropriate survival of damaged cells in the body. Interestingly, 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. Within the last five years, it has emerged that a newly discovered class of non-protein encoding RNAs, microRNAs (miRNAs), can function as tumor suppressor genes and oncogenes, factors which strictly control cellular growth. MiRNAs are small ~22 nucleotide non-coding RNAs and function to negatively regulate expression of their gene targets. MiRNAs typically bind to complementary sequences located in the 3’ untranslated region (3’ UTR) of their target protein-coding messenger RNAs (mRNAs) commonly resulting in translational inhibition and/or mRNA degradation.
My laboratory is very interested in studying how miRNAs control developmental events and how this relates to cancer progression. Specifically, the lab focuses on the lin-4 and let-7 miRNA families, which are found to direct important developmental processes such as cell-fate specification and gonad formation, and which are closely linked to human cancer. My lab employs the nematode, Caenorhabditis elegans, an organism easily grown and studied in the laboratory and amendable to genetic manipulation, to characterize the biological function of the lin-4 and let-7 miRNA homologues during development. We use the nematode as a tool for gene discovery to identify targets specifically regulated by these miRNA families to control cancer-associated processes. We also want to investigate if these miRNA pathways are conserved in mammals and direct proliferation pathways using both in vivo mouse models and mammalian cell culture assays. Furthermore, we are studying how the lin-4 and let-7 miRNA members as well as other miRNA families contribute to urothelial cancers, primarily prostate cancer, and could be used as diagnostic biomarkers. Investigating the function of conserved miRNAs in both nematode and mammalian systems promises to reveal a novel class of cancer progression genes with immense diagnostic and therapeutic potential.
Lewis, H. & Esquela-Kerscher, A. The let-7 microRNA family: Big roles in development and disease. Invited Impact Article for Nature Education. In press.
Lewis, H. & Esquela-Kerscher, A. MicroRNA Epigenetic Systems and Cancer. Invited book chapter for “Systems Biology of Cancer”, Cambridge University Press, Editor: Samual Thiagalingam. In press.
Jo, J & Esquela-Kerscher, A. (2011). A growing molecular toolbox for the functional analysis of microRNAs in Caenorhabditis elegans. Briefings in Functional Genomics. 2011 May 29. [Epub ahead of print].
Esquela-Kerscher, A. MicroRNAs Function as Tumor Suppressor Genes and Oncogenes. Invited book chapter for “MicroRNAs in Development and Cancer”, Imperial College Press, Editor Frank Slack. October 2010.
Breving, K. & Esquela-Kerscher, A.(2010). The Complexities of MicroRNA Regulation: meandering around the rules. Invited review for the Directed Issue on MicroRNAs in Development and Disease for the International Journal of Biochemistry & Cell Biology. Int J Biochem Cell Biol 42, 1316-1329.
Kato, M., Paranjape, T., Ullrich, R., Nallur, S., Gillespie, E., Keane, K., Esquela-Kerscher, A., Weidhaas, J.B., and Slack, F.J. (2009). The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human cells. Oncogene. May 4 [Epub ahead of print].
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. 2008. (*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 Mar 15;7(6):759-64.
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.
Esquela, A.F., Zimmers, T.A., Koniaris, L.G., Sitzman, J.V., and Lee, S.-J. (1997). Transient down-regulation of Inhibin ßC following partial hepatectomy. Biochem Biophys Res Commun 235, 553-556.
McGrath, S.A., Esquela, A.F., and Lee, S.-J. (1995). Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol 9,131-136.