Our research efforts are centered primarily on cancer and are both pre-clinical and translational. One focus is on tumor metabolism. One hypothesis we are testing is whether reversing the Warburg effect will affect tumor cells preferentially. We are using both RNAi and pharmacologic inhibitors to approach this question with a focus on several genes involved in altering the fate of pyruvate. Other studies center on glycolytic enzymes and on pathways that support the Krebs cycle. Yet others focus on inhibitors of fatty acid and cholesterol synthesis. A separate focus is in cancer immunology, where we are searching for drug combinations that alter several immunosuppressive mechanisms that tumors use to escape immune recognition and kill. We have also been cataloguing case reports of cancer remissions on protocols or drug regimens that are not considered standard of care. We are conducting pre-clinical studies to see if any of these therapies have a rationale and, if promising, we are committed to taking them to the clinic for patients with advanced cancer who have exhausted conventional options. In particular, we investigating drugs/therapies that are off patent or were never patented, hence making them unattractive to the pharmaceutical sector. We are co-founders of a not-for-profit organization (GlobalCures) that will develop such therapies for human studies. We are especially interested in promoting drug combinations which have clear-cut mechanisms of action.
Angiogenic signaling via Tie-1 and the promotion of atherosclerosis: Tie-1 is an orphan “receptor” closely related to Tie-2. Both are primarily expressed in endothelial cells. We have discovered a method to activate the Tie-1 receptor and have shown in vitro that this results in the induction of a number of signals that appear to promote atherogenesis. Extension of these data to in vivo studies is in progress.
Boguski MS, Mandl KD, Sukhatme VP. Drug discovery. Repurposing with a difference. Science. 2009 Jun 12;324(5933):1394-5.
Cao P, Hanai JI, Tanksale P, Imamura S, Sukhatme VP, Lecker SH. Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. FASEB J. 2009 Apr 30.
Xie H, Valera VA, Merino MJ, Amato AM, Signoretti S, Linehan WM, Sukhatme VP, Seth P. LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer. Mol Cancer Ther. 2009 Mar;8(3):626-35.
Chan B, Sukhatme VP. Suppression of Tie-1 in endothelial cells in vitro induces a change in the genome-wide expression profile reflecting an inflammatory function. FEBS Lett. 2009 Mar 18;583(6):1023-8.
1984-1992 Howard Hughes Medical Institute investigator
1995 and 1997 Election to young turks (American Society for Clinical Investigation) and old turks (Association of American Physicians)
1998-2002 Board of consulting editors for Journal of Clinical Investigation
2001-present Victor J. Aresty Endowed Chair in Oncology
2000-2004 Co-leader of the Program in Development at the Dana Farber/Harvard Cancer Center
2008-present Director of the Harvard Catalyst Program in Novel Clinical and Translational Methodologies
Major Collaborative Activities:
With Drs. Strom, Koulamanda, Oukka and Lin in tumor immunology.
With Drs. Grant, Lenkinski, and Seth in metabolic tumor imaging.
With Dr. Chan on Tie-1's role in atherogenesis.
