We use transgenic mice to characterize pathways to
cancer, of pancreatic islets, skin, & cervix. Induction of angiogenesis
and acquired resistance to apoptosis appear to be critical determinants
of these pathways. Major goals are to define mechanisms of the angiogenic
switch and of apoptotic control. Another is to identify two candidate
tumor suppressor genes in the islet carcinoma pathway, as a prelude
to studying their functions. We postulate one is an angiogenesis suppressor,
and the other an apoptotic regulator. A new focus is on matrix proteases
which may be components of the angiogneic switch. We also study problems
in immunology, including strategies to elicit immune destruction of
tumors, and a novel thymic cell type implicated in self tolerance.
And, we are testing angiogenesis inhibitors for cancer prevention
and treatment using mouse models of organ-specific cancer. We have
three strategic collaborations that complement our expertise, with:
Judah Folkman on tumor angiogenesis; Joe Gray on tumor suppressor
genetics, and Zena Werb on proteases. Further, we are establishing
a collaboration with a functional genomics company to utilize gene
arrays and genome informatics to characterize the stages of tumorigenesis
by profiling expression of tens of thousands of genes.
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Biomedical Sciences (BMS) Graduate Program
