Fields Cancer research, polyamines, stem cells, polyamine-targeted therapy Alma mater Rutgers University/University of Medicine and Dentistry of New Jersey (PhD)
University of Virginia (BA) Notable awards Eli Lilly Fellowship, Rutgers University (1981–1983)
U.S. Public Health Service Postdoctoral Fellowship (1985–1987)
American Cancer Society Junior Faculty Award (1991–1994) Institutions Lankenau Institute for Medical Research, Wistar Institute | ||
Susan K. Gilmour (born 1953) is an American cancer biologist and professor at Lankenau Institute for Medical Research (LIMR), a biomedical research facility in Wynnewood, Pennsylvania, and part of Main Line Health. Gilmour was elected by her peers to co-chair the 2017 Gordon Research Conference on Polyamines. She is best known for her work on the role and function of polyamines in tumorigenesis. Her research — which has been continuously funded by the National Institutes of Health since 1991 — has contributed to a greater understanding of tumor growth, survival and proliferation, and has earned her national and global recognition
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Education and career
Gilmour earned a BA with distinction in biology from the University of Virginia in 1975. She then attended Memorial Hospital School of Medical Technology (now Danville Regional Medical Center) in Danville, Virginia; became board certified in medical technology by the American Society for Clinical Pathology; and worked from 1976 to 1979 as a senior medical technologist at the Hospital of the University of Pennsylvania. From 1979 to 1981, Gilmour was a pre-doctoral graduate student in the pharmacology department at Thomas Jefferson University. In 1981, she entered the newly formed joint program in toxicology at Rutgers University/University of Medicine and Dentistry of New Jersey, earning Rutgers’ first PhD in toxicology in 1984. As a pre-doctoral Eli Lilly fellow, she studied the role of metabolism in the toxicology and carcinogenicity of benzene.
After receiving her doctorate, Gilmour continued her research at The Wistar Institute in Philadelphia, Pennsylvania, first as postdoctoral fellow (1984 to 1987) and then as research associate (1988 to 1990). While at Wistar, she began her work in characterizing the regulation and expression of ornithine decarboxylase (ODC) in both normal and tumor tissue. Dr. Gilmour joined the scientific research staff at LIMR in 1990 and was appointed professor in 2001. She also has a faculty position in the department of cancer biology at Sidney Kimmel Medical College of Thomas Jefferson University.
Research
Throughout her career, Dr. Gilmour has investigated the role of polyamines and ODC in the growth and proliferation of cancer. Polyamines are ubiquitous small molecules involved in many normal cellular functions, including transcribing and translating genes, regulating ion channels and cell-to-cell interactions, and powering cell growth and replication. ODC is the initial rate-limiting enzyme in polyamine biosynthesis within the cell. Polyamine levels are dramatically elevated in tumor cells compared to normal cells. Her research has explored the effects of polyamines and ODC on the tumor microenvironment, as well as polyamine-targeted therapies designed to help reduce tumor growth.
Another branch of Gilmour’s research involves the role of the blood-clotting enzyme thrombin in tumor growth and metastasis. Cancer has long been known to increase levels of thrombin and to cause hypercoagulability. Dr. Gilmour has investigated the use of anticoagulation therapy to suppress cancer activity while also preventing thrombotic events associated with cancer.
Scientific accomplishments
Scientific discoveries: Dr. Gilmour’s study of polyamines has broadened the scope of medical knowledge about tumor function at the cellular and molecular levels. Using skin-targeted transgenic mice, she demonstrated that elevated levels of ODC play a causal role in the development of tumors. (See also Selected Peer-Reviewed Publications.) She discovered that overexpression of ODC and c-Raf activation is sufficient to convert a normal primary keratinocyte into a malignant, invasive tumor cell. (See Selected Peer-Reviewed Publications.) Using ODC transgenic mouse models, Dr. Gilmour showed that elevated ODC and polyamines promote tumorigenesis via multiple functional mechanisms including increasing proliferation, angiogenesis, chromatin remodeling and invasiveness, while also suppressing the immune response.
Dr. Gilmour provided the first evidence that elevated epidermal levels of polyamines alone can positively affect the recruitment of bulge stem cells in the skin. In the study, reporter mice were used to track stem cells. This finding is significant with regard to the stem cell origin of skin cancer, since carcinogen-targeted stem cells can remain dormant for many years until recruited to develop into a tumor. (See Selected Peer-Reviewed Publications.)
As of 2016, Gilmour has begun an investigation of the role of polyamines in nonmelanoma skin cancer. Arsenic in drinking water exposes millions of people to increased cancer risk, but the means by which arsenic causes cancer are unknown. She recently developed an animal model to study arsenic-induced skin cancer and to demonstrate that in utero exposure to trace levels of arsenic in drinking water leads to skin tumor formation when the animals mature to young adults.
Contributions to clinical practice: In her writings, Dr. Gilmour has suggested that targeting polyamines may disrupt the immunosuppressive mechanisms that allow tumors to thrive. (See Selected Peer-Reviewed Publications.) She has begun evaluating new approaches to disrupting the transport system through which polyamines can be imported into cancer cells. She is conducting preclinical studies of drugs that can selectively deliver antitumor treatments along these chemical pathways. Dr. Gilmour has shown that a novel therapy combining difluoromethylornithine (an ODC inhibitor) with an inhibitor of the polyamine transport system not only blocks tumor growth but also promotes anticancer immune responses — suggesting that such therapy could heighten the effectiveness of both conventional chemotherapy and antitumor immunotherapy. (See Selected Peer-Reviewed Publications.)
In her examination of thrombin’s effects on cancer growth, Dr. Gilmour has demonstrated that the antithrombin drug dabigatran etexilate decreases both the invasion and metastasis of malignant breast and ovarian tumors. In a 2015 study, Dr. Gilmour and her colleagues found that thrombin inhibition significantly enhanced the antitumor and antimetastatic activity of standard chemotherapeutic drugs such as cyclophosphamide and cisplatin. (See Selected Peer-Reviewed Publications.)