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Scientist Profile

Cris Lewis

Senior Director, Biochemical and Cellular Pharmacology
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"I am inspired by the entrepreneurial environment of the Small Molecule effort, as well as the prospect of bringing high-quality science to bear on the discovery of drugs for life-threatening unmet medical needs."

I joined Genentech in January 2006 to head up the Biochemical Pharmacology group in the Small Molecules Division. Our group is responsible for all the biochemical and cellular assays that provide quantitative structure-activity relationship data to guide Medicinal Chemistry efforts. We work together with the Early Leads group to design robust biochemical assays for high-throughput screening, conduct full HTS campaigns with detailed characterization of hits, and provide mechanism of action and selectivity data. We also develop and execute the cellular SAR assays, and contribute as project team members or project leaders all the way into the clinic.

I was attracted to Genentech because I could see that it is an organization that puts great value in high-quality science. More importantly, the strategic decision-making at Genentech is data-driven with a laser focus on the science. The Small Molecule effort is an exciting place to be right now, where we are focused on starting new projects, hiring the very best people, and building a world-class drug discovery organization. Morale is high, fueled by an entrepreneurial spirit and rich scientific discussions.

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My Focus

Our scientists are working on multiple targets in cancer and immunology, from the early stages of protein expression to Clinical trials. We collaborate with Pathway Biologists to characterize targets, develop the most informative cellular assays, and contribute to selection of the best clinical candidate for the therapeutic indication. We work side-by-side with Early Leads Biology and Chemistry in high-throughput screening and hit-to-lead efforts. We collaborate with Structural Biologists in implementation of a structure-based drug design platform for Medicinal Chemistry, and collaborate with DMPK and Pharmaceutical Sciences representatives as the project nears selection of a candidate. There is an excellent bridge between Discovery and our Clinical Sciences group, which is a source of many fruitful discussions about disease states and clinical trial design.

I have the opportunity at the moment to serve as a project leader on a Late-Stage Oncology project that has a molecule in clinical trials, while also serving as a team member on early stage Oncology projects as well. I thoroughly enjoy delving deep into the multi-disciplinary scientific aspects of a project, with the goal of delivering the best drug to patients. Shortly after arriving here, I started up a Project Leader Forum, which offers the Small Molecule Project leaders an opportunity to get together regularly to share knowledge and help build the infrastructure. A good part of my efforts have been devoted to hiring the very best people for our group, and the Small Molecules group. I'm excited by some of the tremendous talent we have attracted to our organization.

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Publications & Recognition
  • Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer.
  • J Med Chem 2010 Feb 11; 53(3): 1086-97.
  • Sutherlin DP, Sampath D, Berry M, Castanedo G, Chang Z, Chuckowree I, Dotson J, Folkes A, Friedman L, Goldsmith R, Heffron T, Lee L, Lesnick J, Lewis C, Mathieu S, Nonomiya J, Olivero A, Pang J, Prior WW, Salphati L, Sideris S, Tian Q, Tsui V, Wan NC, Wang S, Wiesmann C, Wong S, Zhu BY.
  • View Abstract on PubMed
  • Discovery of (R)-6-Cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor.
  • J Med Chem 2009 Feb 11.
  • Li H, Tatlock J, Linton A, Gonzalez J, Jewell T, Patel L, Ludlum S, Drowns M, Rahavendran SV, Skor H, Hunter R, Shi ST, Herlihy KJ, Parge H, Hickey M, Yu X, Chau F, Nonomiya J, Lewis C.
  • View Abstract on PubMed
  • Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.
  • Antimicrob Agents Chemother 2009 Jun; 53(6): 2544-52.
  • Shi ST, Herlihy KJ, Graham JP, Nonomiya J, Rahavendran SV, Skor H, Irvine R, Binford S, Tatlock J, Li H, Gonzalez J, Linton A, Patick AK, Lewis C.
  • View Abstract on PubMed
 
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  • The Scripps Research Institute, La Jolla, California
  • Jane Coffin Childs Postdoctoral Fellow
  • 1990-1993
  • College of Medicine, University of Tennessee, Memphis, TN.
  • Ph.D. in Biochemistry. Department of Biochemistry
  • 1984-1989
  • University of South Florida, Department of Chemistry, Tampa, FL.
  • B.S. in Chemistry, magna cum laude
  • 1980-1983
Publications & Recognition
  • Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer.
  • J Med Chem 2010 Feb 11; 53(3): 1086-97.
  • Sutherlin DP, Sampath D, Berry M, Castanedo G, Chang Z, Chuckowree I, Dotson J, Folkes A, Friedman L, Goldsmith R, Heffron T, Lee L, Lesnick J, Lewis C, Mathieu S, Nonomiya J, Olivero A, Pang J, Prior WW, Salphati L, Sideris S, Tian Q, Tsui V, Wan NC, Wang S, Wiesmann C, Wong S, Zhu BY.
  • View Abstract on PubMed
  • Discovery of (R)-6-Cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor.
  • J Med Chem 2009 Feb 11.
  • Li H, Tatlock J, Linton A, Gonzalez J, Jewell T, Patel L, Ludlum S, Drowns M, Rahavendran SV, Skor H, Hunter R, Shi ST, Herlihy KJ, Parge H, Hickey M, Yu X, Chau F, Nonomiya J, Lewis C.
  • View Abstract on PubMed
  • Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.
  • Antimicrob Agents Chemother 2009 Jun; 53(6): 2544-52.
  • Shi ST, Herlihy KJ, Graham JP, Nonomiya J, Rahavendran SV, Skor H, Irvine R, Binford S, Tatlock J, Li H, Gonzalez J, Linton A, Patick AK, Lewis C.
  • View Abstract on PubMed
  • Clinical poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.
  • Curr Opin Investig Drugs 2007 Dec; 8(12): 1051-6.
  • Lewis C, Low JA.
  • View Abstract on PubMed
  • Structure of the catalytic domain of human polo-like kinase 1.
  • Biochemistry 2007 May 22; 46(20): 5960-71.
  • Kothe M, Kohls D, Low S, Coli R, Cheng AC, Jacques SL, Johnson TL, Lewis C, Loh C, Nonomiya J, Sheils AL, Verdries KA, Wynn TA, Kuhn C, Ding YH.
  • View Abstract on PubMed
  • Identification and structure-based optimization of novel dihydropyrones as potent HCV RNA polymerase inhibitors.
  • Bioorg Med Chem Lett 2006 Sep 15; 16(18): 4834-8.
  • Li H, Tatlock J, Linton A, Gonzalez J, Borchardt A, Dragovich P, Jewell T, Prins T, Zhou R, Blazel J, Parge H, Love R, Hickey M, Doan C, Shi S, Duggal R, Lewis C, Fuhrman S.
  • View Abstract on PubMed
  • Design, synthesis and X-Ray crystallographic studies of [7.3.1] and [8.3.1] macrocyclic FKBP-12 ligands.
  • Bioorg Medicinal Chem Lett 1996 6: 385-390.
  • Babine RE, Bleckman TM, Littlefield ES, Parge, HE, Pelletier LAK, Lewis CT, French JV, Imbacuan M, Katoh S, Tatlock JH, Showalter RE, Villfranca JE.
  • Structure-based design of novel, urea-containing FKBP12 inhibitors.
  • J Med Chem 1996 Apr 26; 39(9): 1872-84.
  • Dragovich PS, Barker JE, French J, Imbacuan M, Kalish VJ, Kissinger CR, Knighton DR, Lewis CT, Moomaw EW, Parge HE, Pelletier LA, Prins TJ, Showalter RE, Tatlock JH, Tucker KD, Villafranca JE.
  • View Abstract on PubMed
  • Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex.
  • Nature 1995 Dec 7; 378(6557): 641-4.
  • Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW, et al.
  • View Abstract on PubMed
  • Medium effects in antibody-catalyzed reactions.
  • Science 1991 Aug 30; 253(5023): 1019-22.
  • Lewis C, Krämer T, Robinson S, Hilvert D.
  • View Abstract on PubMed
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Awards & Honors
  • Fellow of the Jane Coffin Childs Memorial Fund for Medical Research--1990-1993
  • Doggett Predoctoral Fellowship, College of Medicine, University of Tennessee, Memphis--1986-1989
  • Phi Kappa Phi Graduate Fellowship--1984
  • Faculty Scholars Award, University of South Florida, Tampa, Florida--1983
  • Freshman Chemist of the Year Award, University of South Florida, Tampa, Florida--1981
  • United Technologies Tuition Scholarship--1980

Cris Lewis, 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.