The long-term goals of my laboratory are to understand how alterations in the RB1 and TP53 tumor suppressor gene regulatory networks cause cancer. These tumor suppressor genes are two of the most frequently altered genes in human cancer, and understanding how they function at the molecular level will both refine our fundamental understanding of this disease and suggest novel therapeutic approaches to treat it. Our primary experimental approach involves creation of engineered mouse strains with informative genetic mutations, characterizing these mice and their cells to elucidate molecular mechanisms underlying cancer phenotypes, and verifying these mechanisms in human cancer patient specimens.
We study a number of different types of cancer, but our current focus is on prostate cancer. We are addressing several unresolved questions. Does the order or timing of RB1 mutation influence prostate cancer phenotype? Does RB1 mutation facilitate prostate cancer metastasis? Do RNA processing and transport factors contribute to prostate cancer, and could they be used for diagnosis or treatment? How does MDM2 negatively regulate TP53 to cause cancer? Can MDM2 itself be inhibited in unique ways to reactivate TP53 and suppress tumorigenesis?
Chinnam, M., Wang, Y., Zhang, X., Gold, D.L., Khoury, T., Nikitin, A.Yu, Foster, B.A., Li, Y., Bshara, W., Morrison, C.D., Payne Ondracek, R.D., Mohler, J.L., Goodrich, D.W. The Thoc1 Ribonucleoprotein and Prostate Cancer Progression. JNCI J Natl Cancer Inst 106(11): dju306, 2014.
Ko, H.K., Akakura, S., Peresie, J., Goodrich, D.W., Foster, B.A., Gelman, I.H. A transgenic mouse model for early prostate metastasis to lymph nodes. Cancer Res. 74: 945-953, 2014. PMCID:PMC391678
Pitzonka, L., Wang, X., Ullas, S., Wolff, D.W., Wang, Y., Goodrich, D.W. The THO ribonucleoprotein complex is required for stem cell homeostasis in the adult mouse small intestine. Mol. Cell. Biol. 33: 3505-3514, 2013. PMCID:PMC3753850
Sun, H., Wang, Y., Chinnam, M., Zhang, X., Hayward, S.W., Foster, B.A., Nikitin, A.Y., Wills, M., Goodrich, D.W. E2f binding-deficient Rb1 protein suppresses prostate tumor progression in vivo. Proc Natl Acad Sci U S A 108:704-709, 2011. PMCID:PMC3021049
Chinnam, M., and Goodrich, D.W. RB1, development, and cancer. Curr. Top. Dev. Biol. 94: 129-169, 2011. PMCID:PMC3691055