Senior Scientist, Discovery Oncology
years at Genentech
I came to Genentech 7 years ago after completing my postdoctoral fellowship at UCSF. At the time I was deciding whether to pursue a career in academia or a career in industry. In thinking about what motivated me to be a scientist, I realized that the reason I did cancer research was pretty simple. I wanted to help patients, and there’s no place better to do that than Genentech. As an added bonus I get to work with outstanding scientists in a highly collaborative environment.
I’m interested in non-genetic mechanisms of intra-tumoral heterogeneity. Not all tumor cells have the same properties or capacities and individual populations seem to play different roles in the tumorigenic process. There may be a specific population that has innate therapeutic resistance, another that can escape immune detection, another that is highly invasive, etc. The overall properties of a tumor as a whole are really the sum of the capacities of each of these distinct populations. What complicates things further, is that it appears that there is interconversion of cells between populations, which in some cases may be enhanced in response to a stress or stimulus. This is really a fascinating area of research that may have important implications for our approach to treating cancer.
Having the opportunity to mentor postdocs doing true basic research projects is one of the key factors that makes Genentech the unique and highly respected company that it is. Having postdocs in the lab allows us to dive deeply into the biology of cancer, and the mechanisms by which different genes and pathways influence tumor cell heterogeneity, therapeutic resistance and relapse. I really enjoy the opportunity to mentor very smart and driven people, and to see them develop into independent scientists. Postdocs help all of us remember why we love science so much, and they bring an energy and excitement that everyone in the group benefits from.
Notch3 is a marker of tumor-propagating cells in non-small cell lung cancer and is required for their self-renewal.
(2013)Cancer Cell, Jul 8;24(1):59-74. doi: 10.1016
Yanyan Zheng, Cecile C. de la Cruz, Leanne C. Sayles, Chris Alleyn-Chin, Dedeepya Vaka, Tim D. Knaak, Marty Bigos, Yue Xu, Chuong D Hoang, Joseph Shrager, Dorothy French, William Forrest, Zhaoshi Jiang, Erica L. Jackson* and E. Alejandro Sweet-Cordero
In many cases, treatment of solid tumors with standard chemotherapy leads only to partial response. Even after complete responses, many patients will relapse with incurable disease. Thus, tumor recurrence driven by tumor-reinitiating cells (TRICs) is a central problem in cancer therapy. Controversy exists regarding whether tumor re-initiating cells arise stochastically from a genetically diverse tumor population or whether they are a pre-existing subpopulation of tumor cells with innate chemoresistance. Surprisingly, relatively little attention has been focused on studying the process of tumor re-initiation in vivo.
We identify drivers of chemoresistance and disease relapse by comparing the residual chemoresistant cells that are spared by chemotherapy (TRICs) to the bulk tumor cells within the same model. To do this we used several in vivo non-small cell lung cancer (NSCLC) xenograft models that regress in response to chemotherapy. In addition, we used a genetically engineered mouse model in which chemotherapeutic treatment only results in a slowing of tumor growth, as is the case in the majority of patients. We are currently studying growth-factor mediated, epigenetic and other drivers of resistance.
We also study tumor propagating cells (TPCs) in NSCLC. Our studies of TRICs support the idea that tumors contain a pre-existing subpopulation of drug tolerant cells, which may be the same population as the TPCs. We are currently characterizing TRICs isolated from naïve cultures and tumors.
Oncogenic RAS pathway activation promotes resistance to anti-VEGF therapy through G-CSF-induced neutrophil recruitmentProceedings of the National Academy of Sciences, 2013, ISSN: 0027-8424 View on PubMed
Blocking NRG1 and Other Ligand-Mediated Her4 Signaling Enhances the Magnitude and Duration of the Chemotherapeutic Response of Non-Small Cell Lung CancerScience Translational Medicine, 2013, ISSN: 1946-6234 View on PubMed
Lactate Dehydrogenase B is required for the growth of KRAS-dependent lung adenocarcinomasClinical Cancer Research, 2012, ISSN: 1078-0432 View on PubMed
Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacityPloS ONE, 2012, ISSN: 1932-6203 View on PubMed
- Massachusetts Institute of Technology, Dept. of Biology, Ph.D. – 2003
- UCSF Dept. of Neurological Surgery, Postdoctoral Fellow – 2003-2006
- Brandeis University, Dept. of Biology, B.A. – 1995