The Lankenau Institute for Medical Research
Association: Resident Faculty
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.
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
1. Muth A, Kamel J, Kaur N, Shicora AC, Ayene IS, Gilmour SK, Phanstiel O. Development of Polyamine Transport Ligands with Improved Metabolic Stability and Selectivity against Specific Human Cancers. J Medicinal Chem, 56(14):5819-28, 2013.
2. Pigott E, Duhadaway JB, Muller AJ, Gilmour S, Prendergast GC, Mandik-Nayak L. 1-Methyl-tryptophan synergizes with methotrexate to alleviate arthritis in a mouse model of arthritis. Autoimmunity. 47(6):409-18, 2014.
3. Hayes CS, Shicora AC, Keough MP, Snook AE, Burns MR, Gilmour SK. Polyamine-Blocking Therapy Reverses Immunosuppression in the Tumor Microenvironment Cancer Immunol Res. 2(3):274-85, 2014.
4. Hayes CS, DeFeo K, Woster PM, and Gilmour SK. Elevated Ornithine Decarboxylase Activity Promotes Skin Tumorigenesis by Stimulating the Recruitment of Bulge Stem Cells but not via Toxic Polyamine Catabolic Metabolites Amino Acids, 46(3):543-52, 2014.
5. Hayes CS, Burns MR, and Gilmour SK. Polyamine Blockade Stimulates an Anti-Tumor Immune Response Oncoimmunology. 3(1):e27360, 2014.