The People of Tulane Cancer Center Research

Hee-Won ParkHee-Won Park, Ph.D.
Associate Professor of Biochemistry and Molecular Biology Tulane Cancer Center Contributing Member in the Signaling & Clinical Programs

Contact Information
Phone: 504-988-7140
Address: 1430 Tulane Ave., SL-43, New Orleans, LA 70112

Biographical Narrative

Dr. Park received his Ph.D. in molecular biophysics and crystallography from UT Southwestern and completed postdoctoral research in a crystallography laboratory at Duke University Medical Center, which provided him with education and experience in the theoretical and technical aspects of structural biology. As a faculty member at St. Jude Children’s Research Hospital, Memphis, TN, he had an opportunity to be involved in structure-based, lead inhibitor development programs; his laboratory’s role involved the structure determination of target proteins and inhibitor design. Joining the Structural Genomics Consortium and Department of Pharmacology at the University of Toronto was critical for enhancing his career as a structural biologist. His Consortium laboratory developed over-expression systems and purification protocols for over 300 human proteins, identified novel compounds that stabilize the purified proteins, increased the crystalizability of proteins by using protein engineering, and solved the structures of almost 100 proteins alone and/or in complex with ligands. His academic laboratory, in parallel, selected a few potential treatment targets for human diseases based on the structural work of his Consortium laboratory. Specifically, they identified small molecule PKM2 activators inhibiting the growth of xenograft tumors in mice. His lab's structural studies revealed that the activators bound at a site along the PKM2 subunit interface, stabilizing the tetrameric state (a cancer progression-preventing conformation). These data suggest that small molecule activation of pKM2 in tumors is feasible and represents a strategy to interfere with tumor metabolism for cancer therapy. At Tulane, his laboratory continues to develop PKM2 activators as a means to limit tumor growth. In addition, they study the structure and function relationship of dimeric PKM2, which is a culprit linked to cancer progression. As PKM2 is new in anti-tumor drug discovery, he expects the accurate and complete picture of PKM2 regulation will help validate it as a drug target.

Selected Publications
Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A, Yang H, Mattaini KR, Metallo CM, Fiske BP, Courtney KD, Malstrom S, Khan TM, Kung C, Skoumbourdis AP, Veith H, Southall N, Walsh MJ, Brimacombe KR, Leister W, Lunt SY, Johnson ZR, Yen KE, Kunii K, Davidson SM, Christofk HR, Austin CP, Inglese J, Harris MH, Asara JM, Stephanopoulos G, Salituro FG, Jin S, Dang L, Auld DS, Park HW, Cantley LC, Thomas CJ, Vander Heiden MG.Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nature Chem Biol, 8: 839-847, 2012

Siddiqui N, Tempel W, Nedyalkova L, Volpon L, Wernimont AK, Osborne MJ, Park HW, Borden KL. Structural insights into the allosteric effects of 4EBP1 on the eukaryotic translation initiation factor eIF4E. J Mol Biol. 415: 781-792, 2012

Wang H, Hota PK, Tong Y, Li B, Shen L, Nedyalkova L, Borthakur S, Kim S, Tempel W, Buck M, Park HW. Structural basis of Rnd1 binding to Plexin Rho GTPase binding domains (RBDs). J Biol Chem 286:26093-26106, 2011

Jiang J, Boxer MB, Vander Heiden MG, Shen M, Skoumbourdis AP, Southall N, Veith H, Leister W, Austin CP, Park HW, Inglese J, Cantley LC, Auld DS, Thomas CJ. Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg Med Chem Lett 20:3387-3393, 2010

Boxer MB, Jiang JK, Vander Heiden MG, Shen M, Skoumbourdis AP, Southall N, Veith H, Leister W, Austin CP, Park HW, Inglese J, Cantley LC, Thomas CJ. Evaluation of substituted N,N’-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J Med Chem 53:1048-1055, 2010

Allali-Hassani A, Wasney GA, Chau I, Hong BS, Senisterra G, Loppnau P, Shi Z, Moult J, Edwards AM, Arrowsmith CH, Park HW, Schapira M, Vedadi M. A survey of proteins encoded by non-synonymous SNPs reveals a significant fraction with altered stability and activity. Biochemical J 424:15-26, 2009

1430 Tulane Ave, New Orleans, LA 70112