We are interested in cancer cell biology focusing on elucidating signaling pathways which control processes such as cell migration and survival how these signals are misregulated in different diseases. We have a long standing interest in cytoskeletal skaffolding proteins and have used in vivo, ex vivo and in vitro approaches to elucidate their functions in migration of normal and cancerous cells. More recently, we have found links between some of these proteins and proteins involved in a cellular homeostasis process, autophagy. This is a process that has been linked to cancer, aging, neurodegenerative diseases, and cardiovascular diseases. We are interested in elucidating the regulatory network that controls autophagy and understanding how misregulation of this network contributes to breast cancer.
Liu S, Thomas SM, Woodside DG, Rose DM, Kiosses WB, Pfaff M, Ginsberg MH. Paxillin Binding to a4 integrins modifies integrin-dependent biological responses. Nature 1999; 402:676-81.
Hagel M, George EA, Kim A, Tamimi R, Opitz SL, Turner CE, Imamoto A, Thomas SM. The adaptor protein, paxillin, is essential for normal development in the mouse and is a critical transducer of fibronectin signaling. Mol. Cell Biol. 2002, 22:901-15.
Kowalski JR, Egile C, Gil S, Li R, Thomas SM. Cortactin regulates cell migration through activation of N-WASP. J. Cell Sci., 2005 118:79-87.
Chen GC, Turano B, Ruest PJ, Hagel M, Settleman JE, Thomas SM. Regulation of Rho and Rac signaling to the cytoskeleton by paxillin during drosophila development. Mol. Cell. Biol. 2005 25: 979-987.
Chen GC, Lee JY, Tang HW, Debnath J, Thomas SM, Settleman J. Genetic interactions between Drosophila melanogaster Atg1 and paxillin reveal a role for paxillin in autophagosome formation. Autophagy. 2008 Jan-Feb;4(1):37-45.
External Recognition:
Leukemia and Lymphoma Society Scholar; NIH RO1; DOD Breast Cancer Career Development Award; Massachusetts Breast Cancer Award; 2002, 2008 Harvard Medical School BBS Teaching Award; American Cancer Society Scholar; DOD Neurofibromatosis Research Award
Committees:Harvard Medical School BBS Admissions Committee; BIDMC Ph.D. Subcommittee Chair; Harvard School of Public Health GCD Faculty Search Committee; Harvard Medical School BBS Qualifying Exam Committee Chair; Faculty Co-Director of Diversity Programs-Divison of Medical Sciences at HMS; Reviewer for American Cancer Society Development Differentiation and Cancer Study Section; Reviewer, Children's Tumor Foundation
Presentations:
Fred Hutchinson-Salk Institute Signal Transduction Meeting, October 1997; Annual Meeting on Oncogenes, 1999; Gordon Research Conference on Cell Proliferation 1999; Keystone Symposia, Joint Regulation of Signalling Pathways by Integrins and Growth Factors, March 2000; Gordon Conference on Integrin Signaling, 2000; Session Chair, ASCB 2000; Presentations ASCB 2001-2004; Dahlem International Symposium, Berlin Germany; Sept. 2001 HMS Pathology Seminar Series, Dec. 1997; MGH East Cancer Center Seminar Series, March 1998; Brigham and Women's, Dept of Cardiology, Dec. 1998; Scripps Research Institute, Dept. of Vascular Biology May 1999; Dept. of Microbiology, SUNY Stony Brook, April 2000; Van Andel Research Institute, May 2001; John's Hopkins School of Medicine, Dept. of Biol. Chemistry Sept. 2001; University of North Carolina, Dept. of Cell and Dev. Biology, Nov. 2001; University of Connecticut Health Center, Dept. of Gen. and Dev. Biol., February 2002; University of Massachusetts, Amherst, Dept. of Mol. Cellular Biology. December 2002; Joslin Diabetes Center, March 2003; Vanderbilt University, Dept. of Biochemistry May 2003; Oncogene Meeting( organizer), June 2004; BIDMC, Dept. of Pathology, Nov. 2004; Salk-EMBL Oncogene Meeting, August 2005; AACR (mini-symposia Chair), April 2006; Gordon Research Conference, July 2006; ABRCMS Meeting, 2006; MGH Cancer Center, Dec. 2006. Cal State University, Northridge, November 2006; Univ. of Cal., Irvine November 2006; Keystone Symposia, Autophagy and Cell Death Pathways, April 2007; Morehouse College, Dept. of Mathematics and Biology February 2008
Tufts University Medical School, Dept. of Physiology, April 2008; Albany Medical College, Center for Cell Biology and Cancer Research, April 2008; PanAmerican Neurovirology Conference, Guadalajara, Mexico, April 2008
Major Collaborative Activities:
Collaborative project on cortactin's role in actin branching with Dr. Rong Li's lab (Dept. of Cell Biology, HMS). Collaborative project on using Drosophila genetics to understand paxillin function with Dr. Jeff Settleman's lab (MGH Cancer Center). Collaborative project on the role of Cortactin in ICAM-induced transmigration with Dr. Bill Luscinskas's lab (Brigham and Women's Hospital); Collaborative Project with Dr. Peter Howley's lab (Pathology, HMS) on Hic-5 in E6-induced transformation; Collaborative project with Dr. David Sinclair's lab (HMS, Pathology) on effects of resveratrol on autophagy. Collaborative project with Dr. Lewis Cantley's lab on identification of substrate specificity for Ulk family kinases
