DF/HCC Program Affiliation

Member, Lymphoma and Myeloma Program

Research Abstract

My research interests focus on the elucidation of signaling pathways leading to Multiple Myeloma (MM) cell growth, proliferation and migration; they thereby aim to identify potential new therapeutic targets. Specifically I defined the pathophysiologic role of vascular endothelial growth factor (VEGF), protein kinase C (PKC), Src/Hck and the Gab adaptor proteins, lipid rafts/ caveolin, and c-Abl/ c-Jun in Multiple Myeloma. Derived clinical trials are e.g. evaluating the therapeutic role of anti- angiogenic compounds alone or in combination with other novel and conventional therapies to improve MM patient outcome.

Publications

• Podar K, Gouill SL, Zhang J, Opferman JT, Zorn E, Tai YT, Hideshima T, Amiot M, Chauhan D, Harousseau JL, Anderson KC. A pivotal role for Mcl-1 in Bortezomib-induced apoptosis. Oncogene 2007 Jul 23;
  PMID: 17653083
• Podar K, Anderson KC. Inhibition of VEGF signaling pathways in multiple myeloma and other malignancies. Cell Cycle 2007 Mar 1; 6(5):538-42
  PMID: 17351339
• Podar K, Raab MS, Tonon G, Sattler M, Barilà D, Zhang J, Tai YT, Yasui H, Raje N, Depinho RA, Hideshima T, Chauhan D, Anderson KC. Up-Regulation of c-Jun Inhibits Proliferation and Induces Apoptosis via Caspase-Triggered c-Abl Cleavage in Human Multiple Myeloma. Cancer Res 2007 Feb 15; 67(4):1680-1688
  PMID: 17308109
• Podar K, Tonon G, Sattler M, Tai YT, Legouill S, Yasui H, Ishitsuka K, Kumar S, Kumar R, Pandite LN, Hideshima T, Chauhan D, Anderson KC. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proc Natl Acad Sci U S A 2006 Dec 19; 103(51):19478-83
  PMID: 17164332
• Podar K, Raab MS, Zhang J, McMillin D, Breitkreutz I, Tai YT, Lin BK, Munshi N, Hideshima T, Chauhan D, Anderson KC. Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl). Blood 2007 Feb 15; 109(4):1669-77
  PMID: 17023575
• Podar K, Anderson KC. The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood 2005 Feb 15; 105(4):1383-95
  PMID: 15471951
• Podar K, Mostoslavsky G, Sattler M, Tai YT, Hayashi T, Catley LP, Hideshima T, Mulligan RC, Chauhan D, Anderson KC. Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells. J Biol Chem 2004 May 14; 279(20):21658-65
  PMID: 15010462
• Podar K, Tai YT, Cole CE, Hideshima T, Sattler M, Hamblin A, Mitsiades N, Schlossman RL, Davies FE, Morgan GJ, Munshi NC, Chauhan D, Anderson KC. Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells. J Biol Chem 2003 Feb 21; 278(8):5794-801
  PMID: 12482878
• Podar K, Tai YT, Lin BK, Narsimhan RP, Sattler M, Kijima T, Salgia R, Gupta D, Chauhan D, Anderson KC. Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with beta 1 integrin- and phosphatidylinositol 3-kinase-dependent PKC alpha activation. J Biol Chem 2002 Mar 8; 277(10):7875-81
  PMID: 11751905
• Podar K, Tai YT, Davies FE, Lentzsch S, Sattler M, Hideshima T, Lin BK, Gupta D, Shima Y, Chauhan D, Mitsiades C, Raje N, Richardson P, Anderson KC. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood 2001 Jul 15; 98(2):428-35
  PMID: 11435313