Sheila M. Thomas, PhD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-4174
Fax: (617) 667-0610


sthomas@fas.harvard.edu

Sheila M. Thomas, PhD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Director of Diversity and Minority Affairs, Division Of Medical Sciences, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are interested in understanding the role of the cytoskeleton during development and in diseases such as cancer. Specifically, the work in my laboratory is focused on three cytoskeletal proteins. Paxillin and cortactin are targets of the oncogenic tyrosine kinases, v-src and BCR-Abl while Hic-5 may be a potential tumor suppressor gene. In addition, amplification of the human cortactin gene is associated with a certain percentage of breast, head and neck tumors. Paxillin and hic-5 are components of focal adhesions, structures involved in adherence of cells to the extracellular matrix. Cortactin, which is localized to the membrane cytoskeleton, may play a role in regulation of cell shape and in some cases function in regulating cell adhesion. A major approach of my laboratory involves the generation of mice carrying targeted disruptions in these genes. Generation of these mice provides a unique tool to analyze the function of these genes not only in vivo, but also in vitro, through the derivation of cell lines from these animals. By combining genetic, biochemical, and cell biological approaches we hope to 1) understand the role of these genes during development, 2) elucidate the signaling pathways these proteins are involved in, and 3) understand their role in transformation and the metastatic process.

Publications

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  • Mack HI, Zheng B, Asara J, Thomas SM. AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization. Autophagy 2012; 8:1197-214. PubMed
  • Liu Y, Preston R, Thomas SM, Brackenridge A, Carroll PV. Cerebral cavernoma: an emerging long-term consequence of external beam radiation in childhood. Clin Endocrinol (Oxf) 2010; 73:555-60. PubMed
  • Wheeler SE, Suzuki S, Thomas SM, Sen M, Leeman-Neill RJ, Chiosea SI, Kuan CT, Bigner DD, Gooding WE, Lai SY, Grandis JR. Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation. Oncogene 2010; 29:5135-45. PubMed
  • Taoudi Benchekroun M, Saintigny P, Thomas SM, El-Naggar AK, Papadimitrakopoulou V, Ren H, Lang W, Fan YH, Huang J, Feng L, Lee JJ, Kim ES, Hong WK, Johnson FM, Grandis JR, Mao L. Epidermal growth factor receptor expression and gene copy number in the risk of oral cancer. Cancer Prev Res (Phila Pa) 2010; 3:800-9. PubMed
  • Armour SM, Baur JA, Hsieh SN, Land-Bracha A, Thomas SM, Sinclair DA. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging (Albany NY) 2010; 1:515-28. PubMed
  • Miranda MB, Duan R, Thomas SM, Grandis JR, Redner RL, Jones JE, Johnson DE. Gefitinib potentiates myeloid cell differentiation by ATRA. Leukemia 2008; 22:1624-7. PubMed
  • Thomas SM, Ogagan MJ, Freilino ML, Strychor S, Walsh DR, Gooding WE, Grandis JR, Zamboni WC. Antitumor mechanisms of systemically administered epidermal growth factor receptor antisense oligonucleotides in combination with docetaxel in squamous cell carcinoma of the head and neck. Mol Pharmacol 2007; 73:627-38. PubMed
  • King DA, Thomas SM. Big lessons for a healthy future. Nature 2007; 449:791-2. PubMed
  • Liu S, Thomas SM, Woodside DG, Rose DM, Kiosses WB, Pfaff M, Ginsberg MH. Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses. Nature 1999; 402:676-81. PubMed
  • Oh ES, Gu H, Saxton TM, Timms JF, Hausdorff S, Frevert EU, Kahn BB, Pawson T, Neel BG, Thomas SM. Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2. Mol Cell Biol 1999; 19:3205-15. PubMed
  • Thomas SM, Hagel M, Turner CE. Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin. J Cell Sci 1998; 112 ( Pt 2):181-90. PubMed
  • Ishida M, Ishida T, Thomas SM, Berk BC. Activation of extracellular signal-regulated kinases (ERK1/2) by angiotensin II is dependent on c-Src in vascular smooth muscle cells. Circ Res 1998; 82:7-12. PubMed
  • Thomas SM, Brugge JS. Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 1998; 13:513-609. PubMed
  • Rusanescu G, Qi H, Thomas SM, Brugge JS, Halegoua S. Calcium influx induces neurite growth through a Src-Ras signaling cassette. Neuron 1995; 15:1415-25. PubMed
  • Weng Z, Thomas SM, Rickles RJ, Taylor JA, Brauer AW, Seidel-Dugan C, Michael WM, Dreyfuss G, Brugge JS. Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains. Mol Cell Biol 1994; 14:4509-21. PubMed
  • Seidel-Dugan C, Meyer BE, Thomas SM, Brugge JS. Effects of SH2 and SH3 deletions on the functional activities of wild-type and transforming variants of c-Src. Mol Cell Biol 1992; 12:1835-45. PubMed
  • Thomas SM, DeMarco M, D'Arcangelo G, Halegoua S, Brugge JS. Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases. Cell 1992; 68:1031-40. PubMed
  • Kremer NE, D'Arcangelo G, Thomas SM, DeMarco M, Brugge JS, Halegoua S. Signal transduction by nerve growth factor and fibroblast growth factor in PC12 cells requires a sequence of src and ras actions. J Cell Biol 1991; 115:809-19. PubMed
  • Thomas SM, Hayes M, D'Arcangelo G, Armstrong RC, Meyer BE, Zilberstein A, Brugge JS, Halegoua S. Induction of neurite outgrowth by v-src mimics critical aspects of nerve growth factor-induced differentiation. Mol Cell Biol 1991; 11:4739-50. PubMed
  • Lord KA, Abdollahi A, Thomas SM, DeMarco M, Brugge JS, Hoffman-Liebermann B, Liebermann DA. Leukemia inhibitory factor and interleukin-6 trigger the same immediate early response, including tyrosine phosphorylation, upon induction of myeloid leukemia differentiation. Mol Cell Biol 1991; 11:4371-9. PubMed
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