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Faculty Profile

Marc Goalstone, Ph.D., Associate Professor of Medicine

We are involved with determining specific parts of insulin signaling as it relates to atherosclerosis and obesity. In particular, we have found that when arterial smooth muscle cells and fat cells become resistant to insulin’s metabolic actions (i.e., utilization of glucose), they become more sensitive to insulin’s mitogenic signals, and in turn become more proliferative and thus increase in number. For smooth muscle cells, they divide and invade the lumen of the artery and block blood flow. For fat cells, they divide and cause increased obesity that can lead to the risk of cardiovascular diseases. We have determined a key enzyme (farnesyltransferase alpha-subunit) in the mitogenic pathway of insulin signaling that when mutated blocks the proliferative action of insulin on vascular smooth muscle cells and fat cells. This suggests that this enzyme could be a target for pharmaceutical therapy, which would block or slow the processes of atherosclerosis and obesity, and thus decrease the chances of cardiovascular diseases.

  • Girish Sharma and Marc L. Goalstone. (2005) Dominant Negative FTase (DNFTa) inhibits ERK5, MEF2C and CREB activation in adipogenesis. Mol & Cell. Endoc. 245:93-104. PUBMED

  • Curtis Scott Solomon, J. Wayne Leitner, and Marc Lee Goalstone (2003) Dominant Negative a-Subunit of Farnesyl- and Geranylgeranyltransferase Inhibits Insulin-induced Differentiation of 3T3-L1 Pre-adipocytes. J. Int’l. Obesity (27:40-47).

  • Curtis Scott Solomon and Marc Lee Goalstone (2002) Dominant Negative a-Subunit of Farnesyltransferase Inhibits the Mitogenic Effects of Insulin and IGF-1 in MCF-7 Breast Cancer Cells. Biochem. Biophys. Res. Comm. 291:458-465. PUBMED

  • Monica Montagnani, Inga Golovchenko, Injune Kim, Gou Young Koh, Marc L. Goalstone, Ameya N. Mundhekar, Mette Johansen, Dennis F. Kucik, Michael J. Quon, and Boris Draznin (2002) Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. J. Biol. Chem. 277:1794-1799. PUBMED

  • Curits Scott Solomon and Marc L. Goalstone (2001) Dominant Negative Farnesyltransferase a-subunit inhibits insulin mitogenic effects. Biochem. Biophys. Res. Comm. 285:161-166. PUBMED

  • Dwight Klemm, J. Wayne Leitner, Peter Watson, Albina Nesterova, Jane E-B Reusch, Marc L. Goalstone, and Boris Draznin (2001) Insulin – induced adipocyte differentiation: Activation of CREB rescues adipogenesis from the arrest caused by inhibition of prenylation. J. Biol. Chem. 276:28430-28435. PUBMED

  • Marc L. Goalstone, J. Wayne Leitner, Paulos Berhanu, Prem M. Sharma, Jerrold M. Olefsky, and Boris Draznin (2000) Insulin signals to prenyl transferases via the Shc branch of the intracellular signaling. J. Biol. Chem. 276:12805-12812. PUBMED