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Vivek Mittal
Assistant Professor
Ph.D., Jawaharlal
Nehru University, 1994
Tumor microenvironment; angiogenesis; metastasis; RNA interference; mouse
models of cancer; bone marrow transplantation; microRNA and gene expression
profiling
email mittal@cshl.edu,
phone (516) 422-4075/4129, fax (516) 422-4109
The tumor microenvironment, or stoma, represents a heterogeneous population
of cells that play a critical role in cancer initiation, progression and
metastasis. A significant portion of the tumor stoma is bone marrow (BM)
derived. Because of their role in all stages of tumor development, the
BM stromal elements represent attractive therapeutic targets for cancer
prevention.
We use BM transplantation and tumor xenograft models to map the spatial
and temporal windows of BM contribution at different phases of cancer
progression, and expand observations from these studies in physiologically
relevant spontaneous models of tumor progression and metastasis.
By genetically marking the BM and tracking their lineages in vivo, we
have identified the BM-derived endothelial progenitor cells (EPCs) as
the main regulators of the angiogenic switch both in primary tumor progression
and in the development of dormant micrometastasis into macrometastasis.
By specifically marking EPCs in vivo, we have dissected the vascular endothelial
growth factor- and Id1 dependent signaling pathways that are involved
in the mobilization, differentiation, and recruitment of EPCs to the tumors.
Our research also seeks to develop effective anti-angiogenic cancer therapies,
and we have demonstrated that ablation of EPCs impairs progression of
primary tumors and metastatic lesions.
Technologies we developed in the laboratory, such as delivery of transgenes
into the BM stem cells, cell-specific ablation in vivo, imaging and high
throughput genomic analysis are contributing to understanding the role
of the tumor microenvironment in cancer progression.
Please visit Vivek's
Lab home page.
Selected Publications
Nolan, D.J., Ciarrocchi, A., Mellick, A.S., Jaggi, J.S., Bambino, K.,
Gupta, S., Heikamp, E., McDevitt, M.R., Scheinberg, D.A., Benezra, R.,
and Mittal, V. 2007. Bone marrow-derived endothelial progenitor cells
are a major determinant of nascent tumor neovascularization. Genes
Dev. 21: 1546–1558.
Gupta, S., Schoer, R.A., Egan, J.E., Hannon, G.J., and Mittal, V. 2004.
Inducible, reversible and stable RNA interference in mammalian cells.
Proc. Natl. Acad .Sci. USA 101: 1929–1932.
Ruzinova, M.B., Schoer, R.A., Gerald, W., Egan, J.E., Pandolfi, P.P.,
Rafii, S., Manova, K., Mittal, V., and Benezra, R. 2003. Effect of angiogenesis
inhibition by Id loss and the contribution of bone marrow derived endothelial
precuresor cells in spontaneous murine tumors. Cancer Cell 4:
277–289.
Kumar, R., Conklin, D.S., and Mittal, V. 2003. High throughput selection
of effective RNAi probes for gene silencing. Genome Res.
13: 2333–2340.
Stolarov, J., Chang, K., Reiner, A., Rodgers, L., Hannon, G.J., Wigler,
M.H., and Mittal, V. 2001. Design of a retroviral-mediated ecdysone-inducible
system and its application to the expression profiling of the PTEN tumor
suppressor. Proc. Natl. Acad. Sci. USA 98: 13043–13048.
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