Susan K. Gilmour

Susan K. Gilmour
Born 1953 (age 6263)
Fields Cancer research, polyamines, stem cells, polyamine-targeted therapy
Institutions Lankenau Institute for Medical Research
The Wistar Institute
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)
Website
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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.[1] Gilmour was elected by her peers to co-chair the 2017 Gordon Research Conference on Polyamines.[2] 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[3] — has contributed to a greater understanding of tumor growth, survival and proliferation, and has earned her national and global recognition

Education and career

Gilmour earned a BA with distinction in biology from the University of Virginia in 1975.[1] 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.[1] 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.[1] 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).[1] 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.[1] She also has a faculty position in the department of cancer biology at Sidney Kimmel Medical College of Thomas Jefferson University.[4]

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.[5] 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.[6][7] 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.[6] (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.[8] 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.[9]

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.[1] 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.)

Selected Peer-Reviewed Publications

Megosh L, Gilmour SK, Rosson D, Soler AP, Blessing M., Sawicki JA, O’Brien TG (1995). “Increased frequency of spontaneous skin tumors in transgenic mice which overexpress ornithine decarboxylase”. Cancer Res 55 (19): 4205-09. PMID 7671221.

Clifford A, Morgan D, Yuspa SH, Soler AP, Gilmour S (1995). “Role of ornithine decarboxylase in epidermal tumorigenesis”. Cancer Res 55 (8): 1680-86. PMID 7712475.

Gilmour SK, Verma AK, Madara T, O’Brien TG (1987). “Regulation of ornithine decarboxylase gene expression in mouse epidermis and epidermal tumors during two-stage tumorigenesis”. Cancer Res 47 (5): 1221-25. PMID 3815331.

Smith MK, Trempus CS, Gilmour SK (1998). “Co-operation between follicular ornithine decarboxylase and v-Ha-ras induces spontaneous papillomas and malignant conversion in transgenic skin”. Carcinogenesis 19 (8): 1409-15. doi: 10.1093/carcin/19.8.1409. PMID 9744537.

Hogarty MD, Norris MD, Davis K, Liu X, Evageliou NF, Hayes CS, Pawel B, Guo R, Zhao H, Sekyere E, Keating J, Thomas W, Cheng NC, Murray J, Smith J, Sutton R, Venn N, London WB, Buxton A, Gilmour SK, Marshall GM, Haber M (2008). “ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma”. Cancer Res 68 (23): 9735-45. doi: 10.1158/0008-5472.can-07-6866. PMC 2596661. PMID 19047152.

Lan L, Trempus C, Gilmour SK (2000). “Inhibition of ornithine decarboxylase (ODC) decreases tumor vascularization and reverses spontaneous tumors in ODC/Ras transgenic mice”. Cancer Res 60 (20): 5696-5703. PMID 11059762.

Chen Y, Megosh LC, Gilmour SK, Sawicki JA, O’Brien TG (2000). “K6/ODC transgenic mice as a sensitive model for carcinogen identification”. Toxicol Lett 116 (1–2): 27-35. doi: 10.1016/s0378-4274(00)00196-x. PMID 10906419.

Hobbs CA, Gilmour SK (2000). “High levels of intracellular polyamines promote histone acetyltransferase activity resulting in chromatin hyperacetylation”. J Cell Biochem 77 (3): 345-60. PMID 10760944.

Gilmour SK, Avdalovic N, Madara T, O’Brien TG (1985). “Induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol 13-acetate in hamster fibroblasts. Relationship between levels of enzyme activity, immunoreactive protein, and RNA during the induction process”. J Biol Chem 260 (30): 16439-44. PMID 4066717.

Smith MK, Goral MA, Wright JH, Matrisian LM, Morris RJ, Klein-Szanto AJ, Gilmour SK (1997). “Ornithine decarboxylase overexpression leads to increased epithelial tumor invasiveness”. Cancer Res 57 (11): 2104-08. PMID 9187103.

Shore LJ, Soler AP, Gilmour SK (1997). “Ornithine decarboxylase expression leads to translocation and activation of protein kinase CK2 in vivo”. J Biol Chem 272 (19): 12536-43. PMID 9139705.

Hobbs CA, Paul BA, Gilmour SK (2002). “Deregulation of polyamine biosynthesis alters intrinsic histone acetyltransferase and deacetylase activities in murine skin and tumors”. Cancer Res 62 (1): 67-74. PMID 11782361.

Manni A, Wechter R, Gilmour S, Verderame MF, Mauger D, Demers LM (1997). “Ornithine decarboxylase over-expression stimulates mitogen-activated protein kinase and anchorage-independent growth of human breast epithelial cells”. Int J Cancer 70 (2): 175-82. PMID 9009157.

Gilmour SK, Aglow E, O’Brien TG (1986). “Heterogeneity of ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin and in epidermal tumors”. Carcinogenesis 7 (6): 943-47. doi: 10.1093/carcin/7.6.943. PMID 2423265.

Gilmour SK (2007). “Polyamines and nonmelanoma skin cancer”. Toxicol Appl Pharmacol 224 (3): 249-56. doi: 10.1016/j.taap.2006.11.023. PMC 2098876. PMID 17234230.

Gilmour SK, Birchler M, Smith MK, Rayca K, Mostochuk J (1999). “Effect of elevated levels of ornithine decarboxylase on cell cycle progression in skin”. Cell Growth Differ 10 (11): 739-48. PMID 10593650.

Paul B, Hayes CS, Kim A, Athar M, Gilmour SK (2005). “Elevated polyamines lead to the selective induction of apoptosis and inhibition of tumorigenesis by (–)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice”. Carcinogenesis 26 (1): 119-24. doi: 10.1093/carcin/bgh281. PMID 15375010.

Hayes CS, DeFeo K, Lan L, Paul B, Sell C, Gilmour SK (2006). “Elevated levels of ornithine decarboxylase cooperate with Raf/ERK activation to convert normal keratinocytes into invasive malignant cells”. Oncogene 25 (10): 1543-53. doi: 10.1038/sj.onc.1209198. PMID 16278677.

Hobbs CA, Wei G, DeFeo K, Paul B, Hayes CS, Gilmour SK (2006). “Tip60 protein isoforms and altered function in skin and tumors that overexpress ornithine decarboxylase”. Cancer Res 66 (16): 8116-22. doi: 10.1158/0008-5472.can-06-0359. PMID 16912189.

Gilmour SK, Robertson FM, Megosh L, O’Connell SM, Mitchell J, O’Brien TG (1992). “Induction of ornithine decarboxylase in specific subpopulations of murine epidermal cells following multiple exposures to 12-O-tetradecanoylphorbol-13-acetate, mezerein and ethyl phenylpropriolate”. Carcinogenesis 13 (1): 51–56. doi: 10.1093/carcin/13.1.51. PMID 1733573.

DeFeo K, Hayes C, Chernick M, Van Ryn J, Gilmour SK (2010). “Use of dabigatran etexilate to reduce breast cancer progression”. Cancer Biol Ther 10 (10): 1001-08. doi: 10.4161/cbt.10.10.13236. PMID 20798593.

Hayes CS, Shicora AC, Keough MP, Snook AE, Burns MR, Gilmour SK (2014). “Polyamine-blocking therapy reverses immunosuppression in the tumor microenvironment”. Cancer Immunol Res 2 (3): 274-85. doi: 10.1158/2326-6066.cir-13-0120-t. PMC 4101915. PMID 24778323.

Hayes CS, Burns MR, Gilmour SK (2014). “Polyamine blockade promotes antitumor immunity”. Oncoimmunology 3 (1): e27360. doi: 10.4161/onci.27360. PMC 3976981. PMID 24711956.

Evageliou NF, Haber M, Vu A, Laetsch TW, Murray J, Gamble LD, Cheng NC, Liu K, Reese M, Corrigan KA, Ziegler DS, Webber HT, Hayes CS, Pawel BR, Marshall GM, Zhao H, Gilmour SK, Norris MD, Hogarty MD (2016). “Polyamine antagonist therapies inhibit neuroblastoma initiation and progression”. Clin Cancer Res [epub ahead of print] March 24. doi: 10.1158/1078-0432.ccr-15-2539. PMID 27012811.

See also

References

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