Sucheta Telang, M.B.B.S.

Education:

M.B.B.S., Delhi University, India 1993
Internship and Residency, University of Connecticut 1994-1997
Post-doctoral Fellowship, Baylor College of Medicine 1997-2000

Curriculum Vitae

Current Positions:

Associate Professor of Medicine, Pediatrics and Biochemistry & Molecular Biology

Contact Information:

Clinical Translational Research Building, Room 423
University of Louisville
505 S Hancock St.
Louisville, KY 40202, USA
Phone 502-852-3679
Fax 502-852-3661
Email: sucheta.telang@louisville.edu

Research Description:

My laboratory is interested in the metabolism of tumors, more specifically in the function of a family of bifunctional enzymes, the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4), that are involved in the regulation of glycolysis in cancer.  Our current studies are focused on a member of this family, PFKFB4. We recently have found that PFKFB4 plays an important role in the regulation of glycolytic metabolism and that it is critical for the survival of multiple tumor types, particularly under hypoxic conditions, and for tumor growth in vivo. We are now further examining the functions of PFKFB4 with the ultimate goal of validating this enzyme as a possible target for the development of novel small molecule inhibitors. In other collaborative studies, we are also actively involved in the investigation of another family member, PFKFB3. In early work with Jason Chesney, we found that PFKFB3 was required for early embryogenesis and essential for Ras transformation and the growth of tumors in vivo. These studies led to the discovery and development of a novel small molecule inhibitor of PFKFB3 (3PO), of which a clinical candidate derivative (PFK158) is currently being investigated in a phase I clinical trial. In collaboration with Dr. Chesney’s laboratory, current studies are also examining the effects of small molecule inhibition of PFKFB3 in vitro and in vivo.

Literature Cited:

  1. Chesney J., Clark J., Klarer A., Imbert-Fernandez Y., Lane A. and Telang S.§. Fructose-2,6-Bisphosphate synthesis by 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (PFKFB4) is required for the glycolytic response to hypoxia and tumor growth. Oncotarget, 2014. 5(16):6670-86. PMID 25115398
  2. Telang S, Yalcin A, Clem AL, Bucala R, Lane AN, Eaton JW, Chesney J. Ras Transformation Requires Metabolic Control by 6-Phosphofructo-2-Kinase.  Oncogene, 2006, 25(55):7225-34. PMID: 16715124
  3. Telang S, Nelson, K, Lane, A, and Chesney, J.  The Oncoprotein H-RasV12 Increases Mitochondrial Metabolism.  Molecular Cancer, 2007, 6:77-83. PMID: 18053146
  4. Clem, B, Telang, S, Clem, A, Yalcin, A, Meier, J, Simmons, A, Rasku, M, Dean, W, Trent, JO, and Chesney, J. Small Molecule Inhibition of 6-Phosphofructo-2-Kinase Activity Suppresses Established Tumor Growth. Molecular Cancer Therapeutics, 2008, 7(1):110-20. PMID: 18202014
  5. Yalcin A, Clem BF, Simmons A, Lane A, Nelson K, Clem AL, Brock E, Siow D, Wattenberg B, Telang S and Chesney J. Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases. Journal of Biological Chemistry, 2009, 284(36):24223-32. PMID: 19473963
  6. Telang, S, Clem, BF, Klarer, AC, Clem, AL, Trent, JO, Bucala, R and Chesney, J.  Small Molecule Inhibition of 6-Phosphofructo-2-Kinase Suppresses T Cell Activation.  Journal of Translational Medicine, 2012,16;10(1):95. PMID: 22591674.
  7. Clem BF, O'Neal J, Tapolsky G, Clem AL, Imbert-Fernandez Y, Kerr DA 2nd, Klarer A, Redman R, Miller DM, Trent JO, Telang S., Chesney J. Targeting 6-Phosphofructo-2-Kinase (PFKFB3) as a Therapeutic Strategy against Cancer. Molecular Cancer Therapeutics, 2013, 12(8) 1-10. PMID: 23674815
  8. De Bock K, …. Rider M, Van Veldhoven PP, Schuit F, Bartrons R, Hofkens J , Fraisl P, Telang S, DeBerardinis RJ, Schoonjans L, Vinckier S, Chesney J, Gerhardt H, Dewerchin M and Peter Carmeliet. Role of PFKFB3-driven Glycolysis in Vessel Sprouting. Cell, 2013, 154(3):651-63. PMID: 23911327
  9. Schoors S, … Telang S, Cascante M, Chesney J, Dewerchin M and Carmeliet P. Partial and Transient Reduction of Glycolysis by PFKFB3-blockade Reduces Pathological Angiogenesis. Cell Metabolism, 2014,19(1):37-48. PMID: 24332967
  10. Imbert-Fernandez  Y., Spaulding R., Lanceta L., Clem B.F., O’Neal J., Clem A., Telang S.§ and Chesney J§.  Estradiol Stimulates Glucose Metabolism via 6-Phosphofructo-2-Kinase (PFKFB3). In press, Journal of Biological Chemistry, 2014, 289(13):9440-8. PMID: 24515104 (§dual communicating).
  11. Klarer, A.C., O’Neal, J., Imbert-Fernandez, Y., Clem, A.L., Ellis, S.R., Clark, J., Clem, B.F., Chesney, J. and Telang, S. Inhibition of 6-Phosphofructo-2-Kinase (PFKFB3) Induces Autophagy as a Survival Mechanism. Cancer and Metabolism, 2014, 2(1):2. PMID: 24451478
  12. Clem BF, Clem AL, Yalcin A, Goswami U, Arumugam S, Telang S, Trent JO, Chesney J. A novel small molecule antagonist of choline kinase-α that simultaneously suppresses MAPK and PI3K/AKT signaling. Oncogene, 2011, 28;30(30):3370-80. PMID 21423211
  13. Telang S, Rasku MA, Clem AL, Carter K, Klarer AC, Badger WR, Milam RA, Rai SN, Pan J, Gragg H, Clem BF, McMasters KM, Miller DM, and Chesney J. Phase II Trial of the Regulatory T Cell-Depleting Agent, Denileukin Diftitox, in Patients with Unresectable Stage IV Melanoma. BMC Cancer, 2011 13;11(1):515. PMID: 22165955
  14. Chesney J and Telang S. Regulation of glycolytic and mitochondrial metabolism by Ras.  Current Pharmaceutical Biotechnology, 2012, 14(3):251-60. PMID: 22201601 (§dual communicating).
  15. Telang, S, Nelson, KK, Siow, DL, Yalcin, A, Thornburg, JM, Eaton, JW, Clem, AL, Imbert-Fernandez, Y, Klarer, AC, Farghaly, H, Clem, BF, and Chesney J.  Cytochrome c oxidase is activated by the oncoprotein Ras and is required for A549 lung adenocarcinoma growth.  Molecular Cancer, 2012, 11(1):60. PMID: 22917272

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