We have an opening for a talented Post-doctoral Fellow to join the laboratory of Dr. Shiva Malek in the Discovery Oncology Department at Genentech. The focus of the lab is to elucidate the mechanistic basis for how the MAPK pathway regulates KRAS driven tumorigenesis using a variety of approaches including biochemical, cellular and in vivo models. Given our interest in small molecule inhibitors of this pathway, we routinely use chemical biology approaches to dissect mechanisms of regulation and signaling in this pathway. The successful candidate will have experience in biochemistry and mechanistic cellular experimentation (tissue culture, IP western and mass spec, signaling experiments, CRISPR, generation of stable cell lines, various growth assays, IF or high content assays) using mammalian tumor cells. Candidates with strong mechanistic understanding of protein structure and function as well as cancer biology experience are encouraged to apply. The lab has access to state of the art mass spectrometry facilities, a structural biology group, a mouse facility to support in vivo studies, access to small molecule inhibitor libraries as well as access to large cancer genomic datasets.
The qualified individual will possess a Ph.D. in Biochemistry, Cell Biology or related field with a solid publication record with at least one first author publication in a high impact journal. Excellent communication, writing and computational skills as well as a track record of working in highly collaborative environments is a must.
More information about the Malek lab at Genentech:
More information about Genentech’s Postdoctoral Program at Genentech:
Relevant Lab Publications:
Yen I, Shanahan F, Merchant M, Orr C, Hunsaker T, Durk M, La ., Zhang X, Martin S, Lin E, Chan J, Yu Y, Amin D, Neve R, Gustafson A, Foster S, Rudolph J, Klijn C *, Malek S* (2018). Pharmacological induction of RAS-GTP levels confers RAF kinase dependency in KRAS mutant tumors. Cancer Cell, 34: 611-625.
Moore A, Rosenberg S, McCormick F, Malek S* (2020). RAS-targeted therapies: is the undruggable drugged? Nature Reviews Drug Discovery, doi: 10.1038/s41573-020-0068-6.
Liau NPD, Wendorff TJ, Quinn JG, Steffek M, Phung W, Liu P, Tang J, Irudayanathan FJ, Izadi S, Shaw AS, Malek S, Hymowitz SG, Sudhamsu J (2020). Negative regulation of RAF kinase activity by ATP is overcome by 14-3-3-induced dimerization. Nat Struct Mol Biol. 27(2):134-141.
Foster SA, Whalen DM, Özen A, Wongchenko MJ, Yin J, Yen I, Schaefer G, Mayfield JD, Chmielecki J, Stephens PJ, Albacker LA, Yan Y, Song K, Hatzivassiliou G, Eigenbrot C, Yu C, Shaw AS, Manning G, Skelton NJ, Hymowitz SG, Malek S*. (2016) Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2. Cancer Cell 29(4):477-93.
Hymowitz S. and Malek S* (2018). Targeting the MAPK Pathway in RAS Mutant Cancers. Cold Spring Harb Perspect Med. 8(11). pii: a031492.
Foster SA, Klijn C, Malek S* (2016). Tissue-Specific Mutations in BRAF and EGFR Necessitate Unique Therapeutic Approaches. Trends in Cancer. 2(12):699-701.
Haling J, Sudhamsu J, Sideris S, Yen I, Nguyen L, Sandoval W, Phung W, Bravo B, Giannetti A, Peck A, Masselot A, Morales T, Smith D, Brandhuber B, Hymowitz S*, Malek S*. (2014) Structure of the BRAF:MEK complex reveals a kinase independent role for BRAF in MAPK Signaling, Cancer Cell, 26: 402-413.
Hatzivassiliou G, Haling JR, Chen H, Song K, Price S, Heald R, Hewitt JF, Zak M, Peck A, Orr C, Merchant M, Hoeflich KP, Chan J, Luoh SM, Anderson DJ, Ludlam MJ, Wiesmann C, Ultsch M, Friedman LS, Malek S, Belvin M. (2013). Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature. 501(7466):232-6.
G. Hatzivassiliou*, K. Song, I. Yen, B. J. Brandhuber, D. J. Anderson, R. Alvarado, M. J.C. Ludlam, D. Stokoe, S. L. Gloor, G. Vigers, T. Morales, I. Aliagas, B. Liu, S. Sideris, K. P. Hoeflich, B. S. Jaiswal1, S. Seshagiri, H/ Koeppen, M. Belvin, L. S. Friedman, S. Malek* (2010). RAF inhibitors prime wildtype RAF to activate the MAPK pathway and enhance growth. Nature, 464:431-435.