My initial work in the signaling and functional effects of small RAS GTPases focused on the molecular mechanisms of RAS trafficking, and its contributions to cancer. I showed that distinct locations of RAS at the plasma membrane profoundly influenced the ability to facilitate downstream signaling, which led to investigating a novel strategy for pharmacological inhibition of RAS-driven cancers.
a. Michael, J.V., Goldfinger, L.E. Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting. Semin Cancer Biol. 2019 DOI: 10.1016/j.semcancer.2017.11.021
b. Goldfinger, L.E. and Michael, J.V. Regulation of Ras signaling and function by plasma membrane microdomains. Biosci Trends. 2017. 11(1):23-40.DOI: 10.5582/bst.2016.01220. PMID: 28179601
c. Michael, J.V., Wurtzel, J.G.T., Goldfinger, L.E. Regulation of H-Ras-driven MAPK signaling, transformation and tumorigenesis, but not tumor progression, by plasma membrane microdomains. Oncogenesis. 2016. 5(5):e228. DOI: 10.1038/oncsis.2016.36. PMID: 27239960
d. Michael, J.V., Wurtzel, J.G.T., Goldfinger, L.E. Inhibition of Galectin-1 sensitizes H-Ras oncogenesis and tumor progression to Rapamycin treatment. Anticancer Res. 2016. 36(10):5053-5061. PMID: 27798864
Combining my background in oncogenesis and resources in platelet biology, we began focusing our research efforts towards understanding the roles of platelets in cancer. We have found that microvesicles released from platelets, infiltrate solid tumors, adhere to tumor cells, and transfer platelet-derived microRNAs to the tumor cells, with profound effects on tumor cell gene expression, function, and tumorigenesis in vivo.
a. Michael, J.V., Wurtzel, J.G., Mao, G.F., Rao, A.K., Kolpakov, M.A., Sabri, A., Hoffman, N.E., Rajan, S., Tomar, D., Madesh, M., Nieman, M., Yu, J., Edelstein, L.C., Rowley, J.W., Weyrich, A.S., Goldfinger, L.E. Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth. Blood. 2017. 3;130(5):567-580. DOI: 10.1182/blood-2016-11-751099.
b. Rowley, J.W., Chappaz, S., Corduan, A., Chong, M.M.W., Campbell, R., Khoury, A., Manne, B-K., Wurtzel, J.G.T., Michael, J.V., Goldfinger, L.E., Murnaw, M.M., Nieman, M.T., Kile, B.T., Provost, P., and Weyrich, A.S. 2016. Dicer1 mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood. 2016. 127(14):1743-51. DOI: 10.1182/blood-2015-07-661371. Epub 2016 Jan 14. PMID: 26773046