Fischer, Susan M.

Fischer, Susan M. Ph.D.

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Research Interests

Skin carcinogenesis, pancreatic cancer, inflammation, arachidonic acid metabolism, prostaglandins

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 the prostaglandin metabolites of arachidonic acid, cytokines, and growth factors. Studies currently underway are concerned with understanding the specific roles prostaglandin E2 (PGE2) in the development of cancer. We previously showed that overexpression of the enzyme, cyclooxygenase-2 (COX-2), that synthesizes PGE2 confers tumor promoting activity in initiated mouse skin. This indicates that at high levels PGE2 is an endogenous tumor promoter and may be the mechanism by which phorbol esters and UV light, which are known to induce COX-2, function as tumor promoters. To determine the pathophysiological role of PGE2 in carcinogenesis, we are investigating the role of the four EP membrane receptors for PGE2, using knockout and over-expressing mice. We showed that the EP2 receptor contributes to tumor promotion, likely via its ability to upregulate VEGF, cyclin D1 and other genes known to be important to cancer development. Ongoing studies on the EP1 and EP4 receptors suggest that these mice are self-promoting, i.e., no exogenous tumor promoters are required for tumor development following initiation. Current projects are focused on trying to understand the molecular mechanisms by which this occurs, i.e., what signaling pathways are activated by PGE2 and which receptors transduce the 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 pancreatic ductal adenocarcinoma with a 100% penetrance. Current studies are focused on elucidating the mechanisms involved, particularly with regard to the soluble and inflammatory inflammatory components. Additional studies are investigating the effect of obesity-inducing vs calorie-restricted diets on the development of lesions in this model. Studies in progress indicate that energy balance has a strong effect on the development and progression of this disease, in that calorie restriction significantly protects against disease progression. Ongoing work indicates that IGF-1 levels may mediate this effect, i.e., obesity increases circulating IGF-1, calorie restriction reduces it, and genetic reduction of IGF-1 reduces the growth of xenografts of pancreatic cancer cell lines. The relationship between IGF-1 and inflammatory cytokines is currently being explored.

Selected Publications

  1. Ansari KM, Rundhaug JE, Fischer SM. Multiple signaling pathways are responsible for prostaglandin e2-induced murine keratinocyte proliferation, Mol Cancer Res, 6 (6), 1003-16, 2008
  2. Colby JK, Klein RD, McArthur MJ, Conti CJ, Kiguchi K, Kawamoto T, Riggs PK, Pavone AI, Sawicki J, Fischer SM. Progressive metaplastic and dysplastic changes in mouse pancreas induced by cyclooxygenase-2 overexpression, Neoplasia, 10 (8), 782-96, 2008
  3. Rundhaug JE, Fischer SM. Cyclo-oxygenase-2 plays a critical role in UV-induced skin carcinogenesis, Photochem Photobiol, 84 (2), 322-9, 2008
  4. 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
  5. 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
  6. 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
  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. 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

Contact Information


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