Susan K. Gilmour: Difference between revisions

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| alma_mater = Rutgers University/University of Medicine and Dentistry of New Jersey (PhD) <br/>University of Virginia (BA)
| alma_mater = Rutgers University/University of Medicine and Dentistry of New Jersey (PhD) <br/>University of Virginia (BA)
| awards =
| awards =
| website = {{URL|1=[http://www.limr.org}} https://www.mainlinehealth.org/research/lankenau-institute-for-medical-research/researchers/our-faculty/susan-gilmour}}
| website = {{URL|1=[https://www.mainlinehealth.org/research/lankenau-institute-for-medical-research/researchers/our-faculty/susan-gilmour}}


'''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]].<ref> name={{cite web|url=https://www.mainlinehealth.org/research/lankenau-institute-for-medical-research/researchers/our-faculty/susan-Gilmour}}</ref> 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<ref>{{cite web|url=http://grantome.com/|title=Grantome: The entirety of funding information|website=Grantome}}</ref> — has contributed to a greater understanding of tumor growth, survival and proliferation, and has earned her national and global recognition
'''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]].<ref> name={{cite web|url=https://www.mainlinehealth.org/research/lankenau-institute-for-medical-research/researchers/our-faculty/susan-Gilmour}}</ref> 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<ref>{{cite web|url=http://grantome.com/|title=Grantome: The entirety of funding information|website=Grantome}}</ref> — has contributed to a greater understanding of tumor growth, survival and proliferation, and has earned her national and global recognition

Revision as of 19:08, 31 May 2018

{{Infobox scientist | name = Susan K. Gilmour | image = | caption = | birth_date = 1953 (age 70–71) | birth_place = | fields = Cancer research, polyamines, stem cells, polyamine-targeted therapy | workplaces = 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) | awards = | website = [www.mainlinehealth.org/research/lankenau-institute-for-medical-research/researchers/our-faculty/susan-gilmour

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. 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[2] — 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[3] 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[3] As a pre-doctoral Eli Lilly fellow, she studied the role of metabolism in the toxicology and carcinogenicity of benzene.

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)[4] While at Wistar, she began her work in characterizing the regulation and expression of ornithine decarboxylase (ODC) in both normal and tumor tissue. 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.[5]

Research

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.[6] 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.[7][8] 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

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. Using ODC transgenic mouse models, 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.[9]

Taking their findings one step further, Gilmour and her team in 2017 demonstrated that a polyamine blockade therapy (PBT) they developed inhibited the growth of malignant tumors in mice and activated an immune response to those tumors. Tumors of mice treated with PBT showed reductions in myeloid cells that suppress immune attack on tumor cells and significant increases in tumor-specific cytotoxic T cells.[10]

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.[11]

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.[12] She 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.[13]

Contributions to clinical practice

In her writings, Gilmour has suggested that targeting polyamines may disrupt the immunosuppressive mechanisms that allow tumors to thrive. 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. 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.[14]

In her examination of thrombin’s effects on cancer growth, 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.[15]

Selected 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. doi:10.1002/(SICI)1097-4644(20000601)77:3<345::AID-JCB1>3.0.CO;2-P. 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. doi:10.1074/jbc.272.19.12536. PMID 9139705.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  • 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. doi:10.1002/(sici)1097-0215(19970117)70:2<175::aid-ijc7>3.3.co;2-d. 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. 22: 4391–4404. doi:10.1158/1078-0432.ccr-15-2539. PMID 27012811.

See also

References

  1. ^ name= https://www.mainlinehealth.org/research/lankenau-institute-for-medical-research/researchers/our-faculty/susan-Gilmour. {{cite web}}: Missing or empty |title= (help)
  2. ^ "Grantome: The entirety of funding information". Grantome.
  3. ^ a b . [1][dead link]
  4. ^ [2][dead link]
  5. ^ "Archived copy". Archived from the original on 2016-06-28. Retrieved 2016-06-29. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)CS1 maint: archived copy as title (link)
  6. ^ Pegg, Anthony E. (2009). "Mammalian polyamine metabolism and function". IUBMB Life. 61: 880–894. doi:10.1002/iub.230. PMC 2753421.
  7. ^ Clifford, Amy; Morgan, David; Yuspa, Stuart H.; Soler, Alejandro Peralta; Gilmour, Susan (15 April 1995). "Role of Ornithine Decarboxylase in Epidermal Tumorigenesis". Cancer Research. 55 (8): 1680–1686. PMID 7712475 – via cancerres.aacrjournals.org.
  8. ^ Soda, Kuniyasu (11 October 2011). "The mechanisms by which polyamines accelerate tumor spread". Journal of Experimental & Clinical Cancer Research. 30: 95. doi:10.1186/1756-9966-30-95 – via BioMed Central.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ^ 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.
  10. ^ ET, Minton A, Peters MC, Phanstiel O, Gilmour SK. Oncotarget. 2017 Aug 24;8(48):84140-52
  11. ^ Hayes, CS; DeFeo-Mattox, K; Woster, PM; Gilmour, SK (Mar 2014). "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. doi:10.1007/s00726-013-1559-0.
  12. ^ "Data". limr.org.
  13. ^ "News – Lankenau Institute for Medical Research obtains three new grant - Main Line Health - Philadelphia, Pennsylvania".
  14. ^ Bassiri, H; Benavides, A; Haber, M; Gilmour, SK; Norris, MD; Hogarty, MD (Jul 2015). "Translational development of difluoromethylornithine (DFMO) for the treatment of neuroblastoma". Transl Pediatr. 4 (3): 226–38.
  15. ^ Alexander, ET; Minton, AR; Hayes, CS; Goss, A; Van Ryn, J; Gilmour, SK (Sep 2015). "Thrombin Inhibition and Cyclophosphamide Synergistically Block Tumor Progression and Metastasis". Cancer Biol Ther.
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