Fischer, Susan M.

Fischer, Susan M. Ph.D.

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Research Interests

Skin carcinogenesis, pancreatic cancer, inflammation, arachidonic acid metabolism, peroxisome proliferator-activated receptors

Current Research

The primary focus of my laboratory is to elucidate the role of inflammatory processes in the tumor-promotion stage of carcinogenesis. The emphasis of this work is on mediators of inflammation, including arachidonic acid metabolites, cytokines, and growth factors. Studies currently underway are concerned with understanding the regulation of the enzymes involved in arachidonic acid metabolism and the normal and pathophysiological functions of their metabolites. We previously showed that tumor promoters and UV light induce cyclooxygenase -2 (COX-2) and that this enzyme is constitutively overexpressed in tumors. To determine the role of prostaglandins (PGs) in carcinogenesis, we generated COX-2 transgenic mice, targeting the transgene to either keratin-5 or keratin-14-expressing epithelia. These mice develop skin tumors after initiation, in the absence of tumor promoters, suggesting that the PG products of COX-2 have tumor promoting activity. In order to determine the function of PGs, we are investigating the phenotypes and tumor responses of mice over-expressing or deficient in specific PG receptors. We recently showed that mice that are null for the EP2 receptor for PGE2 produce markedly fewer skin tumors and that mice that over-express EP2 develop more tumors. Ongoing studies on the EP1 and EP4 receptors suggest that these mice are self-promoting, ie., no exogenous tumor promoters are required for tumor development following initiation. These projects are focused on trying to understand how PGs act as tumor promoters, i.e., what signaling pathways are activated by PGE2 and which receptors transduce tumor-promoting signals. This information should be useful in designing new approaches to chemoprevention/intervention in skin cancer development.

One of our transgenic mice (K5.COX-2) develops spontaneous pancreatitis that progresses to ductal adenocarcinoma. Current studies are focused on elucidating the mechanisms involved, particularly with regard to the inflammatory component. Additional studies are investigating the effect of obesity-inducing vs calorie-restricted diets on the development of lesions in this model. Ongoing studies indicate that energy balance has a significant effect on the development and progression of this disease.

Selected Publications

  1. Riedel SB, Fischer SM, Sanders BG, Kline K. Vitamin E analog, alpha-tocopherol ether-linked acetic acid analog, alone and in combination with celecoxib, reduces multiplicity of ultraviolet-induced skin cancers in mice, Anticancer Drugs, 19 (2), 175-81, 2008
  2. Rundhaug JE, Fischer SM. Cyclo-oxygenase-2 Plays a Critical Role in UV-induced Skin Carcinogenesis, Photochem Photobiol, 2008
  3. Ansari KM, Sung YM, He G, Fischer SM. Prostaglandin receptor EP2 is responsible for cyclooxygenase-2 induction by prostaglandin E2 in mouse skin, Carcinogenesis, 28 (10), 2063-8, 2007
  4. Fischer SM, Pavone A, Mikulec C, Langenbach R, Rundhaug JE. Cyclooxygenase-2 expression is critical for chronic UV-induced murine skin carcinogenesis, Mol Carcinog, 46 (5), 363-71, 2007
  5. Rundhaug JE, Mikulec C, Pavone A, Fischer SM. A role for cyclooxygenase-2 in ultraviolet light-induced skin carcinogenesis, Mol Carcinog, 46 (8), 692-8, 2007
  6. Rundhaug JE, Pavone A, Kim E, Fischer SM. The effect of cyclooxygenase-2 overexpression on skin carcinogenesis is context dependent, Mol Carcinog, 46 (12), 981-92, 2007
  7. Shen J, Pavone A, Mikulec C, Hensley SC, Traner A, Chang TK, Person MD, Fischer SM. Protein expression profiles in the epidermis of cyclooxygenase-2 transgenic mice by 2-dimensional gel electrophoresis and mass spectrometry, J Proteome Res, 6 (1), 273-86, 2007
  8. He G, Sung YM, Digiovanni J, Fischer SM. Thiazolidinediones inhibit insulin-like growth factor-i-induced activation of p70S6 kinase and suppress insulin-like growth factor-I tumor-promoting activity, Cancer Res, 66 (3), 1873-8, 2006
  9. Sung YM, He G, Hwang DH, Fischer SM. Overexpression of the prostaglandin E2 receptor EP2 results in enhanced skin tumor development, Oncogene, 25 (40), 5507-16, 2006
  10. Sung YM, He G, Fischer SM. Lack of expression of the EP2 but not EP3 receptor for prostaglandin E2 results in suppression of skin tumor development, Cancer Res, 65 (20), 9304-11, 2005

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9570