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Scientist Profile

Shiva Malek

Associate Director, Biochemical and Cellular Pharmacology
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"I am inspired by cancer survivors and their ability to face the unknown with courage, strength, and a will to live. The pictures and stories of patients whose lives we have positively impacted is a source of motivation for me."
 

I came to Genentech in 2006 to help build the growing small molecule drug discovery group, having spent a number of years at smaller biotechnology companies including Vertex Pharmaceuticals and Exelixis.

I am thrilled to be a part of this dynamic department and hope to contribute to Genentech's success in the small molecule arena.

I was born in Iran and moved to the United States when I was 7 years old. Our summer vacation to Logan, Utah in 1978 resulted in a permanent move to the United States. We moved to California in the early 80's and I was lucky enough to take advantage of the University of California system from undergraduate through my Ph.D.

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My Focus

My group is responsible for developing and validating enzyme and cellular assays in order to support small molecule drug discovery projects.

We collaborate closely with scientists from the Pathway Biology groups in order to develop robust assays which are predictive of target biology. We also work closely with other members in the Biochemical Pharmacology, Early Leads, Assay Automation and Technology, and Medicinal Chemistry groups to support projects from high-throughput screening, lead validation, and lead optimization. Our mission is to do high-quality science, maintain a strong project focus, and work collaboratively with other departments at Genentech in order to accelerate small molecule programs into the clinic.

I also serve as the project team leader for one of the early stage research oncology programs. In this capacity, I lead a multi-disciplinary team of scientists across various departments and oversee an external collaboration in order to identify novel development candidates.

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Publications & Recognition
  • RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.
  • Nature 2010 Feb 3. [Epub ahead of print]
  • Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, Ludlam MJ, Stokoe D, Gloor SL, Vigers G, Morales T, Aliagas I, Liu B, Sideris S, Hoeflich KP, Jaiswal BS, Seshagiri S, Koeppen H, Belvin M, Friedman LS, Malek S.
  • View Abstract on PubMed
  • Development of Mechanistic Assays to Differentiate PI3K and mTor Inhibitors.
  • EORTC 2009.
  • Trinh L, Yen I, Lesnick J, Malek S.
  • Understanding the Effects of RAF Inhibitors on RAF Signaling in B-Raf V600E Mutant versus Wildtype Tumors.
  • EORTC 2009.
  • Yen I, Song K, Stokoe D, Liu B, Brandhuber B, Gloor S, Aliagas I, Anderson DJ, Voegtli W, Ludlum MJC, Alvarado R, Sideris S, Ramaswamy S, Heise C, Belvin M, Friedman L, Hatzivassiliou G, Malek S.
 
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  • University of California, San Diego
  • Ph.D., Biochemistry
  • 2000
  • University of California, Irvine
  • M.S., Chemistry
  • 1995
  • University of California, Los Angeles
  • B.S., Biochemistry
  • 1993
Publications & Recognition
  • RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.
  • Nature 2010 Feb 3. [Epub ahead of print]
  • Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, Ludlam MJ, Stokoe D, Gloor SL, Vigers G, Morales T, Aliagas I, Liu B, Sideris S, Hoeflich KP, Jaiswal BS, Seshagiri S, Koeppen H, Belvin M, Friedman LS, Malek S.
  • View Abstract on PubMed
  • Development of Mechanistic Assays to Differentiate PI3K and mTor Inhibitors.
  • EORTC 2009.
  • Trinh L, Yen I, Lesnick J, Malek S.
  • Understanding the Effects of RAF Inhibitors on RAF Signaling in B-Raf V600E Mutant versus Wildtype Tumors.
  • EORTC 2009.
  • Yen I, Song K, Stokoe D, Liu B, Brandhuber B, Gloor S, Aliagas I, Anderson DJ, Voegtli W, Ludlum MJC, Alvarado R, Sideris S, Ramaswamy S, Heise C, Belvin M, Friedman L, Hatzivassiliou G, Malek S.
  • Understanding the role of Raf signaling in B-RafV600E mutant and wildtype tumors.
  • EORTC 2008.
  • Hatzivassiliou G, Sideris S, Yen I, Gloor S, Callejo M, Brandhuber B, Liu B, Belvin M, Malek S.
  • Identification of small molecule modulators of pathological huntington protein structure.
  • In preparation 2007.
  • Malek S, Straley K, Yuan R, Stack J, Pollock.
  • X-ray crystal structure of an IκBα x NF-κB p65 homodimer complex.
  • J Biol Chem 2003 Jun 20; 278(25): 23094-100.
  • Malek S, Huang DB, Huxford T, Ghosh S, Ghosh G.
  • View Abstract on PubMed
  • IκBα, but not IκBα, functions as a classical cytoplasmic inhibitor of NF-κB dimers by masking both NF-κB nuclear localization sequences in resting cells.
  • J Biol Chem 2001 Nov 30; 276(48): 45225-35.
  • Malek S, Chen Y, Huxford T, Ghosh G.
  • View Abstract on PubMed
  • Preparation and crystallization of dynamic NF-κB:IκB complexes.
  • J Biol Chem 2000 Oct 20; 275(42): 32800-6.
  • Huxford T, Malek S, Ghosh G.
  • View Abstract on PubMed
  • Mechanism of κB DNA binding by Rel/NF-κB dimers.
  • J Biol Chem 2000 Aug 11; 275(32): 24392-9.
  • Phelps CB, Sengchanthalangsy LL, Malek S, Ghosh G.
  • View Abstract on PubMed
  • Structure and mechanism in NF-κB/IκB signaling.
  • Cold Spring Harb Symp Quant Biol 1999; 64: 533-40.
  • Huxford T, Malek S, Ghosh G.
  • View Abstract on PubMed
  • The crystal structure of the IκBα/NF-κB complex reveals mechanisms of NF-κB inactivation.
  • Cell 1998 Dec 11; 95(6): 759-70.
  • Huxford T, Huang DB, Malek S, Ghosh G.
  • View Abstract on PubMed
  • IκBα functions through direct contacts with the nuclear localization signals and the DNA binding sequences of NF-κB.
  • J Biol Chem 1998 Sep 25; 273(39): 25427-35.
  • Malek S, Huxford T, Ghosh G.
  • View Abstract on PubMed
  • Structure of a G.T.A triplet in an intramolecular DNA triplex.
  • Biochemistry 1992 May 26; 31(20): 4838-46.
  • Wang E, Malek S, Feigon J.
  • View Abstract on PubMed
  • Structure and stability of X.G.C mismatches in the third strand of intramolecular triplexes.
  • Science 1991 Oct 11; 254(5029): 270-4.
  • Macaya RF, Gilbert DE, Malek S, Sinsheimer JS, Feigon J.
  • View Abstract on PubMed
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Awards & Honors
  • Pre-doctoral Fellowship, American Heart Association
    University of California, San Diego, Department of Chemistry and Biochemistry
    1998-2000
  • Molecular Biophysics Training Grant, National Institute of Health
    University of California, San Diego, Department of Chemistry and Biochemistry
    1996-1998
  • Outstanding Teaching Assistant
    University of California, San Diego, Department of Chemistry and Biochemistry
    1996-1997
  • Graduate Research Traineeship, National Science Foundation
    University of California, Irvine, Department of Chemistry
    1994-1995
  • Outstanding Research Award in Biochemistry, Emory University, School of Medicine
    University of California, Los Angeles, Department of Chemistry and Biochemistry
    1993
  • Outstanding Research Proposal, UCLA Association of Chemists and Biochemists
    University of California, Los Angeles, Department of Chemistry and Biochemistry
    1991
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Ellen Filvaroff, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.