My research interests lie in the pathogenesis of colorectal neoplasms. A key area of focus is the clinical consequences of developing tumors with inactivation of the DNA mismatch repair system. My lab has investigated the effect of chemotherapeutic agents, particularly 5-fluorouracil, in patients…
more and in cell models without an intact mismatch repair system, and has shown that the mismatch repair system binds to 5-fluorouracil that is incorporated into DNA and this recognition is a mode to mediate cellular toxicity. This has implications on the choice of therapy for patients with colorectal cancer based on the biology of the tumor in addition to staging. The lab also investigates differences in genomic instability based on race, as there are marked differences in colorectal cancer rates and mortality among different racial groups. The lab has focused on the TGFBR2 and ACVR2 genes that are targeted for mutation as a consequence of loss of DNA mismatch repair. In vitro and in vivo models have been generated to calculate accurate mutation rates for these genes in various mismatch repair-deficient backgrounds, as well as the effects of these target genes on contributing to the neoplastic process. As a consequence, my lab is also determining how TGFβ family members including BMP, activin, and TGFβ, convert from tumor suppression in early neoplasia to tumor proliferation in advanced cancers and metastasis.
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