 Aurora Esquela-Kerscher, Ph.D.
Assistant Professor
Adjunct Professor
The College of William & Mary
Department of Applied Science
Lewis Hall, #3047
Office: (757) 446-7191
Email: kerschAE@evms.edu
Biomedical Sciences Program
Track:
Molecular Integrative Biosciences (MIB)
Education
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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. 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 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's 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.
The 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. She uses the nematode
as a tool for gene discovery to identify targets
specifically regulated by these miRNA families to control
cancer-associated processes. The lab is also investigating
whether these miRNAs and their targets are evolutionarily
conserved and control similar proliferation pathways in
mammals using both mouse models and mammalian cell culture.
Furthermore, Dr. Kerscher
intends to capitalize on the lab's unique mouse lung cancer
model to determine the role of the lin-4 and let-7 miRNA
families in tumor formation and extend findings to oncogenic
pathways involved in urothelial cancers, primarily prostate
cancer. Using both nematode and mammalian systems, her work
promises to reveal miRNAs as a major class of cancer
prevention genes with immense therapeutic potential.
Selected Publications
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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).
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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.)
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Esquela-Kerscher, A.,
and Slack, F.J. (2006). Oncomirs – MicroRNAs with a role
in cancer. Nature Reviews Cancer 6, 259-269.
(Featured cover article)
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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.
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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.
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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.
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Esquela-Kerscher, A.,
and Slack, F.J. (2004). News and Views: The age of
high-throughput microRNA profiling.
Nature Meth 1, 106-107.
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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)
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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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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.
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McGrath, S.A., Esquela,
A.F., and Lee, S.-J. (1995). Oocyte-specific
expression of growth/differentiation factor-9.
Mol Endocrinol 9,131-136.
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