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 JM, Thomas SM. AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization. Autophagy 2012; 8:1197-214. 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