DEPARTMENT OF PATHOLOGY

Jay Desgrosellier, Ph.D.

Jay Desgrosellier, Ph.D.

  • Assistant Professor
  • B.A. – Whitman College, 1997
  • Ph.D. – Vanderbilt University, 2004

Research Interests

Our research focuses on mechanisms of tumor progression and metastasis, particularly in breast cancer. Specifically, we are interested in the signaling pathways that control stem cell behavior, both in the adult mammary gland and aggressive breast tumors. Toward this end, we employ a multidisciplinary approach focused on elucidating integrin αvβ3 signaling pathways in normal mammary stem cells with the goal of identifying potential pharmacological targets in aggressive “stem-like” tumor cells that will reduce mortality from breast cancer.

Our findings have provided surprising insights into a particular population of mammary stem cells present during pregnancy. We found that αvβ3 expression acts as a switch during early pregnancy to activate stem cells, and is then turned-off in late pregnancy, allowing stem cells to return to a quiescent state. This dynamic regulation of αvβ3 is critical for epithelial remodeling of the adult mammary gland during pregnancy and may represent a conserved mechanism found in epithelial cells from other adult organs. We are currently investigating whether this newly identified role for αvβ3 may be to blame for “stem-like” properties associated with αvβ3 expression in breast cancers, including pregnancy-associated breast cancer, a disease that primarily occurs in young women and is associated with frequent metastasis.

Additionally, we are interested in the signaling pathways surrounding αvβ3 that are necessary for stemness in the adult mammary gland and aggressive breast cancers. This includes upstream molecules such as growth factors and cytokines capable of inducing αvβ3 expression, in addition to the kinases and transcription factors downstream of αvβ3 that lead to cellular reprogramming. The goal of these studies is to elucidate key molecules that contribute to “stem-like” properties in breast cancer cells and identify new therapeutic approaches for treating breast cancer recurrence and metastasis.

Representative Publications

  1. Desgrosellier, JS, Barnes, LA, Shields, DJ, Huang, M, Lau, SK, Prevost, N, Tarin, D, Shattil, SJ, Cheresh, DA. (2009). An integrin αvβ3-c-Src oncogenic unit promotes anchorage-independence and tumor progression. Nat Med 15(10), 1163-9. PMCID: PMC2759406
  2. Desgrosellier, JS, Cheresh, DA. (2010). Integrins in cancer: Biological implications and therapeutic opportunities. Nat Rev Cancer 10(1), 9-22.
  3. Shields, DJ, Murphy, EA, Desgrosellier, JS, Mielgo, A, Lau, SK, Barnes, LA, Lesperance, J, Huang, M, Schmedt, C, Tarin, D, Lowy, AM, Cheresh, DA. (2011). Oncogenic Ras/Src cooperativity in pancreatic neoplasia. Oncogene 30(18), 2123-2134. PMCID: PMC3104672
  4. Garmy-Susini, B, Avraamides, CJ, Desgrosellier, JS, Schmid, MC, Foubert, P, Ellies, LG, Lowy, AM, Blair, SL, VandenBerg, SR, Datnow, B, Wang, H-Y, Cheresh, DA and Varner, J. (2013). PI3Kα activates integrin α4β1 to establish the metastatic niche in lymph nodes. Proc Natl Acad Sci USA 110(22), 9042-9047. PMCID: PMC3670313
  5. Seguin, L, Kato, S, Franovic, A, Camargo, MF, Lesperance, J, Elliott, KC, Yebra, M, Mielgo, A, Lowy, AM, Husain, H, Cascone, T, Diao, L, Wang, J, Wastuba, Il, Heymach, JV, Lippman, SM, Desgrosellier, JS, Anand, S, Weis, SM, and Cheresh, DA. (2014). An integrin αvβ3-KRAS-RalB complex drives tumour stemness and resistance to EGFR inhibition. Nat Cell Biol 16(5), 457-68.
  6. Desgrosellier, JS, Lesperance, J, Seguin, L, Gozo, M, Kato, S, Franovic, A, Yebra, M, Shattil, SJ and Cheresh, DA. (2014). Integrin αvβ3 drives Slug activation and stemness in the pregnant and neoplastic mammary gland. Dev Cell 30(3), 295-308.
  7. Click here to search for Dr. Desgrosellier's publications

Biography

Dr. Desgrosellier received his B.A. in Biology and Chemistry from Whitman College in Walla Walla, WA. He then received his Ph.D. in Pharmacology from Vanderbilt University with a fellowship from the Pharmaceutical Research and Manufacturers of America (PhRMA) foundation. As a postdoctoral fellow in Dr. David Cheresh’s laboratory, initially at the Scripps Research Institute and then relocated to UCSD, he discovered a surprising adhesion-independent role for the integrin αvβ3 that promoted tumor cell metastasis. This finding initiated his interest in adult stem cell biology and its relevance to cancer, now a major topic of his research as an independent investigator. Dr. Desgrosellier was promoted to Assistant Professor in the Department of Pathology in 2014.

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