Scientist Profile

I came to Genentech in 2004 because of the commitment here to strong basic research as well as a fantastic opportunity to head up a group dedicated to integrating genetically engineered mouse models of oncology into novel target and drug validation efforts.

Genentech offers a unique cultural environment that tries to capture the best of both academia and industry, where creativity and taking risks are not only valued, but encouraged.

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My Focus

We are interested in developing and applying genetically engineered mouse models (GEMMs) of cancer to target identification and validation efforts as well as pre-clinical therapeutic assessment of novel agents and approved drugs. Working with these models in the research setting at Genentech comprises a unique opportunity to test and characterize such novel agents.

Currently, the efforts of the GEMM group are focused on modeling human lung, pancreatic, colon, and prostate cancer in ways that faithfully mirror their human counterparts. Importantly, these models closely recapitulate the disease etiology where tumor-initiating cells are activated in a microenvironment that maintains the tumor-normal cell interactions, including the immune and vascular systems. In addition, some of our efforts are focused on interrogating normal and tumor stem cells and how they impact the various stages of tumorigenesis and therapeutic responsiveness.

Some of the studies in my lab are focused on using GEMMs of non-small cell lung cancer (NSCLC) to investigate the Ras pathway and ErbB family members. To exploit the full power & utility of GEMMs, we are trying to develop novel viral platforms and libraries to facilitate screening efforts both in vitro and in vivo. Ideally, these systems will allow us to interrogate targets of interest by RNAi at defined stages of tumorigenesis and to ultimately identify and gain a better understanding of the cooperating targets and pathways that influence NSCLC tumor initiation, progression, maintenance and drug responsiveness.

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Publications & Recognition

• Using genetically engineered mouse models of cancer to aid drug development: an industry perspective.
• Clin Cancer Res 2006 Sep 15; 12(18): 5312-28.
• Singh M, Johnson L.
• View Abstract on PubMed

• The adenoviral E1B-55k and E4orf6 early gene products promote functional replication in human primary cells by preventing premature and abortive cell death.
• Cancer Cell 2004 6(6): 611-623.
• O'Shea C*, Johnson L*, Bagus B, Shen A, Boyle L, Kunich J, McCormick F. (*Both authors contributed equally to this work.)

• Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease.
• J Clin Invest 2004 Feb; 113(4): 528-38.
• Chan IT, Kutok JL, Williams IR, Cohen S, Kelly L, Shigematsu H, Johnson L, Akashi K, Tuveson DA, Jacks T, Gilliland DG.
• View Abstract on PubMed