Photo of Vikas P. Sukhatme,  MD, ScD

Vikas P. Sukhatme, MD, ScD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-9050
Fax: (617) 667-7843


vsukhatm@bidmc.harvard.edu

Vikas P. Sukhatme, MD, ScD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Victor J. Aresty Professor of Medicine, Medicine, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Tumor metabolism (2006-present)

We have initiated several studies in tumor metabolism. We are testing whether reversing the Warburg effect will affect tumor cells preferentially. This appears to be the case. We are using both RNAi and pharmacologic inhibitors to approach this question with a focus on several genes involved with altering the fate of pyruvate. Other studies are focused on inhibitors of fatty acid and cholesterol synthesis. Yet others focus on a gene in the pentose phosphate pathway and on inhibition of various mitochondrial targets and the ways in which mitochondria signal to canonical oncogenic pathways in the cytosol. We are also examining strategies to decrease intracellular pH by inhibiting export of protons. We are collaborating with MRI experts in our radiology department to non-invasively visualize metabolic fluxes using hyperpolarized carbon substrates.

Tumor immunotherapy (2007-present)

We have initiated studies in tumor immunology with the aim of breaking the tolerant state engendered by tumors. The focus is on defining how tumors generate a population of suppressor cells known as myeloid derived suppressor cells. We are characterizing these cells molecularly by defining novel surface markers that and assaying for drug combinations that in vivo will simultaneously inhibit both these cells and T regulatory cells. Initial studies are in melanoma and pancreatic, lung and breast cancer models in both genetically engineered and transplant systems.

“Outside of the box” cancer therapies (2005-present)

We are cataloguing case reports of cancer remissions on protocols or drug regimens that are not considered standard of care. We are also scouring published preclinical data in cancer models using FDA approved non-cancer drugs (see below) that might be interesting to take to the clinic. We are conducting additional pre-clinical studies especially with such drugs in combinations and are committed to taking them to the clinic for patients with advanced cancer who have exhausted conventional options. We are also 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 aims to develop such therapies for human studies. We are especially interested in promoting drug combinations which have clear-cut mechanisms of action.

 

Publications

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  • Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-itraconazole as an anti-cancer agent. Ecancermedicalscience 2015; 9:521. PubMed
  • Xie H, Hanai JI, Ren JG, Kats L, Burgess K, Bhargava P, Signoretti S, Billiard J, Duffy KJ, Grant A, Wang X, Lorkiewicz PK, Schatzman S, Bousamra M, Lane AN, Higashi RM, Fan TW, Pandolfi PP, Sukhatme VP, Seth P. Targeting Lactate Dehydrogenase-A Inhibits Tumorigenesis and Tumor Progression in Mouse Models of Lung Cancer and Impacts Tumor-Initiating Cells. Cell Metab 2014. PubMed
  • Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-mebendazole as an anti-cancer agent. Ecancermedicalscience 2014; 8:443. PubMed
  • Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP, Vikas P. The Repurposing Drugs in Oncology (ReDO) Project. Ecancermedicalscience 2014; 8:442. PubMed
  • Ren JG, Seth P, Clish CB, Lorkiewicz PK, Higashi RM, Lane AN, Fan TW, Sukhatme VP. Knockdown of malic enzyme 2 suppresses lung tumor growth, induces differentiation and impacts PI3K/AKT signaling. Sci Rep 2014; 4:5414. PubMed
  • Husain Z, Seth P, Sukhatme VP. Tumor-derived lactate and myeloid-derived suppressor cells: Linking metabolism to cancer immunology. Oncoimmunology 2014; 2:e26383. PubMed
  • Chan B, Sukhatme VP. One-step purification of soluble recombinant human 6-phosphogluconate dehydrogenase from Escherichia coli. Protein Expr Purif 2013; 92:62-6. PubMed
  • Chan B, VanderLaan PA, Sukhatme VP. 6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by regulating receptor tyrosine kinase c-Met. Biochem Biophys Res Commun 2013; 439:247-51. PubMed
  • Husain Z, Huang Y, Seth P, Sukhatme VP. Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol 2013; 191:1486-95. PubMed
  • Cerdeira AS, Rajakumar A, Royle CM, Lo A, Husain Z, Thadhani RI, Sukhatme VP, Karumanchi SA, Kopcow HD. Conversion of Peripheral Blood NK Cells to a Decidual NK-like Phenotype by a Cocktail of Defined Factors. J Immunol 2013; 190:3939-48. PubMed
  • Arnaout R, Buck TP, Roulette P, Sukhatme VP. Predicting the cost and pace of pharmacogenomic advances: an evidence-based study. Clin Chem 2013; 59:649-57. PubMed
  • Daemen A, Griffith OL, Heiser LM, Wang NJ, Enache OM, Sanborn Z, Pepin F, Durinck S, Korkola JE, Griffith M, Hur JS, Huh N, Chung J, Cope L, Fackler MJ, Umbricht C, Sukumar S, Seth P, Sukhatme VP, Jakkula LR, Lu Y, Mills GB, Cho RJ, Collisson EA, van't Veer LJ, Spellman PT, Gray JW. Modeling precision treatment of breast cancer. Genome Biol 2014; 14:R110. PubMed
  • Sun X, Han L, Seth P, Bian S, Li L, Csizmadia E, Junger WG, Schmelzle M, Usheva A, Tapper EB, Baffy G, Sukhatme VP, Wu Y, Robson SC. Disordered purinergic signaling and abnormal cellular metabolism are associated with development of liver cancer in Cd39/Entpd1 null mice. Hepatology 2012. PubMed
  • Sukhatme VP, Chan B. Glycolytic cancer cells lacking 6-phosphogluconate dehydrogenase metabolize glucose to induce senescence. FEBS Lett 2012; 586:2389-95. PubMed
  • Wagner BK, Gilbert TJ, Hanai J, Imamura S, Bodycombe NE, Bon RS, Waldmann H, Clemons PA, Sukhatme VP, Mootha VK. A small-molecule screening strategy to identify suppressors of statin myopathy. ACS Chem Biol 2011; 6:900-4. PubMed
  • Hanai JI, Doro N, Sasaki AT, Kobayashi S, Cantley LC, Seth P, Sukhatme VP. Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen-actiated protein kinase (MAPK) and phosphatidylinositol-3- kinase (PI3K)/AKT pathways. J Cell Physiol 2011. PubMed
  • Seth P, Grant A, Tang J, Vinogradov E, Wang X, Lenkinski R, Sukhatme VP. On-target inhibition of tumor fermentative glycolysis as visualized by hyperpolarized pyruvate. Neoplasia 2011; 13:60-71. PubMed
  • Bhatt RS, Merchan J, Parker R, Wu HK, Zhang L, Seery V, Heymach JV, Atkins MB, McDermott D, Sukhatme VP. A phase 2 pilot trial of low-dose, continuous infusion, or "metronomic" paclitaxel and oral celecoxib in patients with metastatic melanoma. Cancer 2010; 116:1751-6. PubMed
  • Ren JG, Seth P, Everett P, Clish CB, Sukhatme VP. Induction of erythroid differentiation in human erythroleukemia cells by depletion of malic enzyme 2. PLoS ONE 2010. PubMed
  • 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; 23:2844-54. PubMed
  • Boguski MS, Mandl KD, Sukhatme VP. Drug discovery. Repurposing with a difference. Science 2009; 324:1394-5. PubMed
  • 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; 583:1023-8. PubMed
  • Chan B,Sukhatme VP. Receptor tyrosine kinase EphA2 mediates thrombin-induced upregulation of ICAM-1 in endothelial cells in vitro. Thromb Res 2008; 123:745-52. PubMed
  • 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; 8:626-35. PubMed
  • Wei F,Karihaloo A,Yu Z,Marlier A,Seth P,Shibazaki S,Wang T,Sukhatme VP,Somlo S,Cantley LG. Neutrophil gelatinase-associated lipocalin suppresses cyst growth by Pkd1 null cells in vitro and in vivo. Kidney Int 2008; 74:1310-8. PubMed
  • Bhatt RS, Landis DM, Zimmer M, Torregrossa J, Chen S, Sukhatme VP, Iliopoulos O, Balk S, Bubley GJ. Hypoxia-inducible factor-2alpha: effect on radiation sensitivity and differential regulation by an mTOR inhibitor. BJU Int 2008; 102:358-63. PubMed
  • Chan B, Yuan HT, Ananth Karumanchi S, Sukhatme VP. Receptor tyrosine kinase Tie-1 overexpression in endothelial cells upregulates adhesion molecules. Biochem Biophys Res Commun 2008; 371:475-9. PubMed
  • Gallagher DC,Parikh SM,Balonov K,Miller A,Gautam S,Talmor D,Sukhatme VP. Circulating angiopoietin 2 correlates with mortality in a surgical population with acute lung injury/adult respiratory distress syndrome. Shock 2007; 29:656-61. PubMed
  • Zeidel M, Bonventre J, Forrest J, Sukhatme V. A national course for renal fellows: the origins of renal physiology. J Am Soc Nephrol 2008; 19:649-50. PubMed
  • Giuliano JS, Lahni PM, Harmon K, Wong HR, Doughty LA, Carcillo JA, Zingarelli B, Sukhatme VP, Parikh SM, Wheeler DS. Admission angiopoietin levels in children with septic shock. Shock 2007; 28:650-654. PubMed
  • Hanai J, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, Kishi S, Yamashita M, Phillips PS, Sukhatme VP, Lecker SH. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest 2007; 117:3940-51. PubMed
  • Yuan HT, Venkatesha S, Chan B, Deutsch U, Mammoto T, Sukhatme VP, Woolf AS, Karumanchi SA. Activation of the orphan endothelial receptor Tie1 modifies Tie2-mediated intracellular signaling and cell survival. FASEB J 2007; 21:3171-83. PubMed
  • Mammoto T, Parikh SM, Mammoto A, Gallagher D, Chan B, Mostoslavsky G, Ingber DE, Sukhatme VP. Angiopoietin-1 requires p190 RhoGAP to protect against vascular leakage in vivo. J Biol Chem 2007; 282:23910-8. PubMed
  • Hakime A, Hines-Peralta A, Peddi H, Atkins MB, Sukhatme VP, Signoretti S, Regan M, Goldberg SN. Combination of radiofrequency ablation with antiangiogenic therapy for tumor ablation efficacy: study in mice. Radiology 2007; 244:464-70. PubMed
  • Gallagher DC, Bhatt RS, Parikh SM, Patel P, Seery V, McDermott DF, Atkins MB, Sukhatme VP. Angiopoietin 2 is a potential mediator of high-dose interleukin 2-induced vascular leak. Clin Cancer Res 2007; 13:2115-20. PubMed
  • Bhatt RS, Seth P, Sukhatme VP. Biomarkers for monitoring antiangiogenic therapy. Clin Cancer Res 2007; 13:777s-780s. PubMed
  • Atkins MB, Ernstoff MS, Figlin RA, Flaherty KT, George DJ, Kaelin WG, Kwon ED, Libermann TA, Linehan WM, McDermott DF, Ochoa AC, Pantuck AJ, Rini BI, Rosen MA, Sosman JA, Sukhatme VP, Vieweg JW, Wood CG, King L. Innovations and challenges in renal cell carcinoma: summary statement from the second cambridge conference. Clin Cancer Res 2007; 13:667s-70s. PubMed
  • Mochida Y, Parisuthiman D, Kaku M, Hanai J, Sukhatme VP, Yamauchi M. Nephrocan, a novel member of the small leucine-rich repeat protein family, is an inhibitor of transforming growth factor-beta signaling. J Biol Chem 2006; 281:36044-51. PubMed
  • Venkatesha S, Hanai J, Seth P, Karumanchi SA, Sukhatme VP. Lipocalin 2 antagonizes the proangiogenic action of ras in transformed cells. Mol Cancer Res 2006; 4:821-9. PubMed
  • Hu G, Tang J, Zhang B, Lin Y, Hanai J, Galloway J, Bedell V, Bahary N, Han Z, Ramchandran R, Thisse B, Thisse C, Zon LI, Sukhatme VP. A novel endothelial-specific heat shock protein HspA12B is required in both zebrafish development and endothelial functions in vitro. J Cell Sci 2006; 119:4117-26. PubMed
  • Hines-Peralta A, Sukhatme V, Regan M, Signoretti S, Liu ZJ, Goldberg SN. Improved tumor destruction with arsenic trioxide and radiofrequency ablation in three animal models. Radiology 2006; 240:82-9. PubMed
  • Merchan JR, Tang J, Hu G, Lin Y, Mutter W, Tong C, Karumanchi SA, Russell SJ, Sukhatme VP. Protease activity of urokinase and tumor progression in a syngeneic mammary cancer model. J Natl Cancer Inst 2006; 98:756-64. PubMed
  • Tang J, Hu G, Hanai J, Yadlapalli G, Lin Y, Zhang B, Galloway J, Bahary N, Sinha S, Thisse B, Thisse C, Jin JP, Zon LI, Sukhatme VP. A critical role for calponin 2 in vascular development. J Biol Chem 2005; 281:6664-72. PubMed
  • Seth P, Lin Y, Hanai J, Shivalingappa V, Duyao MP, Sukhatme VP. Magic roundabout, a tumor endothelial marker: expression and signaling. Biochem Biophys Res Commun 2005; 332:533-41. PubMed
  • Karumanchi SA, Maynard SE, Stillman IE, Epstein FH, Sukhatme VP. Preeclampsia: a renal perspective. Kidney Int 2005; 67:2101-13. PubMed
  • Hanai J, Mammoto T, Seth P, Mori K, Karumanchi SA, Barasch J, Sukhatme VP. Lipocalin 2 diminishes invasiveness and metastasis of Ras-transformed cells. J Biol Chem 2005; 280:13641-7. PubMed
  • Merchan JR, Jayaram DR, Supko JG, He X, Bubley GJ, Sukhatme VP. Increased endothelial uptake of paclitaxel as a potential mechanism for its antiangiogenic effects: potentiation by Cox-2 inhibition. Int J Cancer 2004; 113:490-8. PubMed
  • Merchan JR, Chan B, Kale S, Schnipper LE, Sukhatme VP. In vitro and in vivo induction of antiangiogenic activity by plasminogen activators and captopril. J Natl Cancer Inst 2003; 95:388-99. PubMed
  • Strom TB, Sukhatme VP. A refined understanding of immunosuppressives and cancer risk. Kidney Int 2003; 63:1160-1. PubMed
  • Lin LF, Zhu G, Yoo JJ, Soker S, Sukhatme VP, Atala A. A system for the enhancement of adenovirus mediated gene transfer to uro-epithelium. J Urol 2002; 168:813-8. PubMed
  • Karumanchi SA, Jiang L, Knebelmann B, Stuart-Tilley AK, Alper SL, Sukhatme VP. VHL tumor suppressor regulates Cl-/HCO3- exchange and Na+/H+ exchange activities in renal carcinoma cells. Physiol Genomics 2001; 5:119-28. PubMed
  • Karumanchi SA, Jha V, Ramchandran R, Karihaloo A, Tsiokas L, Chan B, Dhanabal M, Hanai JI, Venkataraman G, Shriver Z, Keiser N, Kalluri R, Zeng H, Mukhopadhyay D, Chen RL, Lander AD, Hagihara K, Yamaguchi Y, Sasisekharan R, Cantley L, Sukhatme VP. Cell surface glypicans are low-affinity endostatin receptors. Mol Cell 2001; 7:811-22. PubMed
  • Hanna NN, Seetharam S, Mauceri HJ, Beckett MA, Jaskowiak NT, Salloum RM, Hari D, Dhanabal M, Ramchandran R, Kalluri R, Sukhatme VP, Kufe DW, Weichselbaum RR. Antitumor interaction of short-course endostatin and ionizing radiation. Cancer J 2000; 6:287-93. PubMed
  • Yokoyama Y, Green JE, Sukhatme VP, Ramakrishnan S. Effect of endostatin on spontaneous tumorigenesis of mammary adenocarcinoma in a transgenic mouse model. Cancer Res 2000; 60:4362-5. PubMed
  • Hari D, Beckett MA, Sukhatme VP, Dhanabal M, Nodzenski E, Lu H, Mauceri HJ, Kufe DW, Weichselbaum RR. Angiostatin induces mitotic cell death of proliferating endothelial cells. Mol Cell Biol Res Commun 2000; 3:277-82. PubMed
  • Colorado PC, Torre A, Kamphaus G, Maeshima Y, Hopfer H, Takahashi K, Volk R, Zamborsky ED, Herman S, Sarkar PK, Ericksen MB, Dhanabal M, Simons M, Post M, Kufe DW, Weichselbaum RR, Sukhatme VP, Kalluri R. Anti-angiogenic cues from vascular basement membrane collagen. Cancer Res 2000; 60:2520-6. PubMed
  • Yokoyama Y, Dhanabal M, Griffioen AW, Sukhatme VP, Ramakrishnan S. Synergy between angiostatin and endostatin: inhibition of ovarian cancer growth. Cancer Res 2000; 60:2190-6. PubMed
  • Kamphaus GD, Colorado PC, Panka DJ, Hopfer H, Ramchandran R, Torre A, Maeshima Y, Mier JW, Sukhatme VP, Kalluri R. Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J Biol Chem 2000; 275:1209-15. PubMed
  • Bullock AJ, Zhang L, AM O’Neill, Percy A, Sukhatme V, Mier JW, Atkins MB, Bhatt RS. Plasma angiopoietin-2 (ANG2) as an angiogenic biomarker in renal cell carcinoma (RCC) 2010.
  • Cohen HT, Zhou M, Welsh AM, Zarghamee S, Scholz H, Mukhopadhyay D, Kishida T, Zbar B, Knebelmann B, Sukhatme VP. An important von Hippel-Lindau tumor suppressor domain mediates Sp1-binding and self-association. Biochem Biophys Res Commun 1999; 266:43-50. PubMed
  • Lu H, Dhanabal M, Volk R, Waterman MJ, Ramchandran R, Knebelmann B, Segal M, Sukhatme VP. Kringle 5 causes cell cycle arrest and apoptosis of endothelial cells. Biochem Biophys Res Commun 1999; 258:668-73. PubMed
  • Dhanabal M, Volk R, Ramchandran R, Simons M, Sukhatme VP. Cloning, expression, and in vitro activity of human endostatin. Biochem Biophys Res Commun 1999; 258:345-52. PubMed
  • Ananth S, Knebelmann B, Gr. Transforming growth factor beta1 is a target for the von Hippel-Lindau tumor suppressor and a critical growth factor for clear cell renal carcinoma. Cancer Res 1999; 59:2210-6. PubMed
  • Dhanabal M, Ramchandran R, Waterman MJ, Lu H, Knebelmann B, Segal M, Sukhatme VP. Endostatin induces endothelial cell apoptosis. J Biol Chem 1999; 274:11721-6. PubMed
  • McDonald GA, Zhu G, Li Y, Kovesdi I, Wickham TJ, Sukhatme VP. Efficient adenoviral gene transfer to kidney cortical vasculature utilizing a fiber modified vector. J Gene Med 2000; 1:103-10. PubMed
  • Ramchandran R, Dhanabal M, Volk R, Waterman MJ, Segal M, Lu H, Knebelmann B, Sukhatme VP. Antiangiogenic activity of restin, NC10 domain of human collagen XV: comparison to endostatin. Biochem Biophys Res Commun 1999; 255:735-9. PubMed
  • Cook J, Krishnan S, Ananth S, Sells SF, Shi Y, Walther MM, Linehan WM, Sukhatme VP, Weinstein MH, Rangnekar VM. Decreased expression of the pro-apoptotic protein Par-4 in renal cell carcinoma. Oncogene 1999; 18:1205-8. PubMed
  • Dhanabal M, Ramchandran R, Volk R, Stillman IE, Lombardo M, Iruela-Arispe ML, Simons M, Sukhatme VP. Endostatin: yeast production, mutants, and antitumor effect in renal cell carcinoma. Cancer Res 1999; 59:189-97. PubMed
  • Gorski DH, Mauceri HJ, Salloum RM, Gately S, Hellman S, Beckett MA, Sukhatme VP, Soff GA, Kufe DW, Weichselbaum RR. Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin. Cancer Res 1998; 58:5686-9. PubMed
  • Mauceri HJ, Hanna NN, Beckett MA, Gorski DH, Staba MJ, Stellato KA, Bigelow K, Heimann R, Gately S, Dhanabal M, Soff GA, Sukhatme VP, Kufe DW, Weichselbaum RR. Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature 1998; 394:287-91. PubMed
  • Knebelmann B, Ananth S, Cohen HT, Sukhatme VP. Transforming growth factor alpha is a target for the von Hippel-Lindau tumor suppressor. Cancer Res 1998; 58:226-31. PubMed
  • Drummond IA, Goodyer P, Sukhatme VP. Immortal, developmentally arrested human fetal kidney cell lines created by retroviral expression of human papilloma virus E6 and E7. Exp Nephrol 1997; 5:390-8. PubMed
  • Mukhopadhyay D, Knebelmann B, Cohen HT, Ananth S, Sukhatme VP. The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity. Mol Cell Biol 1997; 17:5629-39. PubMed
  • Tsiokas L, Kim E, Arnould T, Sukhatme VP, Walz G. Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2. Proc Natl Acad Sci U S A 1997; 94:6965-70. PubMed
  • Cohen HT, Bossone SA, Zhu G, McDonald GA, Sukhatme VP. Sp1 is a critical regulator of the Wilms' tumor-1 gene. J Biol Chem 1997; 272:2901-13. PubMed
  • Mukhopadhyay D, Tsiokas L, Sukhatme VP. Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res 1995; 55:6161-5. PubMed
  • Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 1995; 375:577-81. PubMed
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