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Assistant Professor of Pharmacology and Cancer Biology
Duke University School of Medicine
Durham, NC 27710
The major goal of our laboratory is to use mouse models to understand the origins and consequences of intratumor heterogeneity. In particular, we are interested in exploring the stresses that tumors encounter during their development, and understanding how these stresses act as selective pressures that shape the clonal architecture of tumors. Further, we aim to explore how this heterogeneity contributes to critical aspects of tumor progression, including metastasis, dormancy, resistance to therapy, and recurrence.
As one window into these questions, we are studying the tumor suppressor par-4. Par-4 is heterogeneously down-regulated in primary tumors, and tumor cells with par-4 down-regulation have an increased propensity to metastasize, persist as dormant cells, and recur following targeted therapy. We are exploring the molecular mechanisms of par-4 down-regulation and how this promotes tumor progression.
James V. Alvarez, George K. Belka, Minghua Xu, Tien-chi Pan, Sharon Sudarshan, Chien-Chung Chen, Blanche Young, Kathleen Notarfrancesco, Valentina Circiumaru, Eric Blankemeyer, Abass Alavi, Joel Karp, and Lewis A. Chodosh. Oncogene-specific regulation of glycolytic enzymes controls FDG uptake in mouse mammary tumors. Submitted, 2013.
James V. Alvarez, Tien-chi Pan, Jason Ruth, Yi Feng, Alice Zhou, Dhruv Pant, Joshua S. Grimley, Thomas J. Wandless, Angela DeMichele, the I-SPY1 Trial Investigators, and Lewis A. Chodosh. Par-4 down-regulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy. Cancer Cell. 2013 Jul 8;24(1):30-44.
Chien-Chung Chen, Douglas B. Stairs, Robert B. Boxer, George K. Belka, Nelson D. Horseman, James V. Alvarez, and Lewis A. Chodosh. Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways. Genes & Development. 2012 Oct 1; 26(12).
James V. Alvarez, Elizabeth S. Yeh, Yi Feng, and Lewis A. Chodosh. Oncogene Addiction: Mouse Models and Clinical Relevance for Molecularly Targeted Therapies, in Genetically Engineered Mice for Cancer Research. 2012.
Chien-Chung Chen, Robert B. Boxer, Douglas B. Stairs, Carla P. Portocarrero, Rachel H. Horton, James V. Alvarez, Morris J. Birnbaum, and Lewis A. Chodosh. Akt is required for Stat5 activation and mammary differentiation. Breast Cancer Res. 2010 Sep 17;12(5):R72.
Zhandong Liu, Min Wang, James V. Alvarez, Megan E. Bonney, Chien-chung Chen, Celina D’Cruz, Tien-chi Pan, Mahlet G Tadesse and Lewis A. Chodosh. Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo. Genome Biology. 2008 Dec;9(12):R180
James V. Alvarez, Heidi Greulich, William R. Sellers, Matthew Meyerson, and David A. Frank. Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor. Cancer Research 2006 March 15;66(6):3162-8.
James V. Alvarez, Philip G. Febbo, Sridhar Ramaswamy, Massimo Loda, Andrea L. Richardson, David A. Frank. Identification of a genetic signature for activated STAT3 in human tumors. Cancer Research 2005 June 15;65(12):5054-5062.