Susan Gilmour, PhD

Photo of Susan Gilmour

Email:  Gilmour@limr.org

Phone: 484.476.8429

Fax: 484.476.2201

Office: R131

Department: Faculty

Association: Resident Faculty

Education:

  • B.A., Biology, University of Virginia, Charlottesville VA, 1975
  • ASCP Board Certified in Medical Technology, 1977
  • Ph.D. Toxicology, Rutgers University, Piscataway NJ, 1984
  • Postdoctoral Fellow, The Wistar Institute, Philadelphia PA, 1984-87

Current Appointments:

  • 2001 to Present: Professor, Lankenau Institute for Medical Research
  • 2000 to Present: Associate Professor, Dept. of Pathology, Anatomy and Cell Biology, Thomas Jefferson University
  • 2004 to Present:  Adjunct Professor of Graduate Biology, St. Joseph's University
  • 2006 to Present:  Adjunct Professor of Pathology, Drexel University
  • 2003 to Present: Associate Editor, Cancer Research
  • 2009 DOD Breast Cancer Research Study Section
  • 2009 NIH Oncology-2 Translational Clinical IRG Study Section

Research Interests:

  • Polyamines and tumorigenesis, tumor microenvironment, tumor immune response, angiogenesis, stem cells, wound healing in skin
  • Google Scholar page

Lab Personnel:

  • Candace Sewter, Biomedical Research Assistant II 
  • Allyson Schicora, Biomedical Research Assistant  
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Lay Description:


Through three projects, Dr. Gilmour is defining mechanisms by which the micro-environment of a normal cell contributes to transform it into a cancer cell.  Her work may ultimately lead to better ways to either prevent or treat various types of cancer.

Polyamines are small molecules that stimulate the growth and proliferation of normal cells. Interestingly polyamine levels increase in many cancers. In a one project, Dr. Susan Gilmour is elucidating mechanisms by which polyamines promote cancer by acting on the immune response, new blood vessel development, and tissue-regenerating cells (i.e. stem cells). Dr. Gilmour has already demonstrated that increased polyamine levels activate a kind of tissue remodeling that is normally seen during wound healing and that promotes the development of cancer. To better treat cancer, Dr. Gilmour is currently investigating ways to inhibit the tumor promoting effects of high levels of polyamines by using compounds found in our diet or compounds that block polyamine activity. In a second project, Dr. Gilmour is investigating whether inhibition of thrombin, a substance typically associated with blood coagulation, can block breast tumor progression. This latest project is based on the observation that in breast cancer, intravascular coagulation increases with cancer progression and is associated with poor prognosis. It is thought that thrombin may directly contribute to cancer spread. Dr. Gilmour's work will provide important preclinical evidence to support the use of an anti-thrombin agent in the treatment of women with breast cancer. In a third project, Dr. Gilmour's group studies how aging facilitates the formation and progression of cancer.

Scientific Description:


Since everyone has some DNA damage in their cells, an important question is whether we can do anything to prevent cancer progression even after cells are damaged.  Our lab is interested in finding ways to block the development of tumors from stem-like cells that harbor genetic lesions but can lie dormant in our bodies for many years.  We have genetically engineered mice that are predisposed to skin tumor development and, thus, mimic individuals at high risk for developing cancer.  These animals possess two genetic lesions that are commonly found in the majority of human tumors: an activated Ras and high levels of ornithine decarboxylase (ODC), a rate-limiting enzyme in the biosynthesis of polyamines.  Polyamines are essential for the growth and differentiation of all cells.  We have demonstrated that the expression of just these two proteins, an activated Ras and ODC, is sufficient to transform a normal primary keratinocyte into a malignant, invasive tumor cell.  A premise of our research efforts is that chemotherapeutic strategies that interfere with signaling events that are downstream from elevated levels of ODC and polyamines will be effective at treating and preventing cancer.  To address this goal, my lab has several distinct but integrated projects that investigate how polyamines modulate 1) the recruitment of stem cells, 2) the crosstalk between ODC-overexpressing epithelial cells and the underlying stromal cells, 3) the formation of reactive stroma, 4) the immune response, 5) normal wound healing in the skin, 6) angiogenesis, and 7) the development of skin tumors.

Dr. Gilmour's Google Scholar page

Selected Publications

  1. Hogarty M.D., Norris, M., Davis, K., Liu, X., Evageliou, N., Hayes, C., Pawel, B., Guo, R., Zhao, H., Sekyere, E., Keating, J., Thomas, W., Cheng, N., Murray, J., Smith, J., Sutton, R., Venn, N., London, W., Buxton, A., Gilmour, S.K., Marshall, G., and Haber, M., (2008) ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma, Cancer Res., 68:9735-9745.
  2. Wei, G., DeFeo, K., Hayes, C., Woster, P., Mandik-Nayak, L., and Gilmour, S.K., (2008) Elevated Ornithine Decarboxylase levels activate ATM - DNA damage signaling in normal keratinocytes, Cancer Res., 68:2214-2222.
  3. Wei, G., Hobbs, C., DeFeo, K., Hayes, C.S., and Gilmour, S.K., (2007) Polyamine-mediated regulation of protein acetylation in murine skin and tumors, Mol. Carcinog., 46:611-617.
  4. Gilmour, S.K., (2007) Polyamines and nonmelanoma skin cancer, Toxicol. Appl. Pharmacol., 224:249-256. 
  5. Hobbs, C.A., Wei, G., DeFeo, K., Paul, B., Hayes, C., and Gilmour, S.K., (2006) Abundant Tip60 protein isoforms and altered function in Ornithine Decarboxylase-overexpressing skin and tumors, Cancer Res., 66:8116-8122.
  6. Lawson, K., Larentowicz, L., Hayes, C., Artim, S., and Gilmour, S. (2006) A novel protein kinase CK2 substrate indicates CK2 is not directly stimulated by polyamines in vivo, Biochemistry, 45:1499-1510. 
  7. Hayes, C.S., DeFeo, K., Lan, L., Paul, B., Sell, C., and Gilmour, S. (2006) Elevated levels of Ornithine Decarboxylase cooperate with Raf/ERK activation to convert normal keratinocytes into invasive malignant cells. Oncogene, 25:1543-1553.
  8. Lawson, K., Larentowicz, L., Laury-Kleintop, L., and Gilmour, S. (2005) B23 is a downstream target of polyamine-modulated CK2. Mol. Cell. Biochem., 274:103-114.
  9. Paul B, Hayes CS, Kim A, Athar M, and Gilmour SK. (2005). Elevated polyamines lead to selective induction of apoptosis and inhibition of tumorigenesis by (-)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice. Carcinogenesis 26: 119-126.
  10. Hobbs, C., Paul, B., and Gilmour, S. (2002) Deregulation of polyamine biosynthesis alters intrinsic histone acetytransferase and deacetylase activities in murine skin and tumors. Cancer Res. 62:67-74. 

  11. Gilmour, S.K., Teti, K.A., Wu, K.Q., and Morris, R.J. (2001). A simple in vivo system for studying epithelialization, hair follicle formation and invasion using primary epidermal cells from wild-type and transgenic ornithine decarboxylase-overexpressing mouse skin. J. Invest. Dermatology, 117:1674-1676. 
  12. Lan, L., Trempus, C., and Gilmour, S. (2000). Inhibition of ornithine decarboxylase decreases tumor vascularization and reverses spontaneous tumors in ODC/Ras transgenic mice. Cancer Res. 60:5696-5703.
 
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