Sharon Campbell, Ph.D.
Deparment of Biomedical Sciences
James H. Quillen Collge of Medicine
PO Box 70582
Room A005 Stanton Gerber Hall (Bldg. 178)
VA Medical Center
Phone: (423) 439-2024
Fax: (423) 439-2030
1992 – B.S., Chemistry, East Tennessee State University, Johnson City, TN
2001 – Ph.D., Biochemistry, James H. Quillen College of Medicine, Johnson City, TN
My research focuses on determining the molecular mechanisms involved in the chemoprevention of prostate and colon cancers by dietary components. Prostate and colon cancers have great country-to-country variation in incidence suggesting the importance of nutrition and environmental factors. Mediterranean societies, with diets rich in vitamin E isoforms, have a lower risk for colon cancer than those of northern Europe and the Americas. In addition, diets rich in antioxidants including vitamin E have protective effects against the development of cancer.
There are eight naturally occurring compounds that can be metabolized by the human body as vitamin E. The phenolic and heterocyclic rings comprise the chroman head group that is common to both the tocopherol and tocotrienol isoforms of vitamin E. The tocopherols have a phytyl tail with three chiral carbons. The tocotrienols have three unsaturated bonds on a farnesyl tail. The isoforms differ as to whether there a is methyl group or a hydrogen located in the R positions on the chroman head.
We have tested the alpha, gamma and delta isoforms and discovered they have variable potencies for induction of cancer cell death both among cancer types and between isoforms. We have tested gamma tocopherol in an azoxymethane animal for colon cancer and have discovered that at 30IU/day of gamma tocopherol is chemopreventive. Further investigations in this model will be ongoing to determine what signaling pathways are involved in the chemopreventive action of gamma tocopherol. Our research in the prostate cell lines has led us to explore the ability of these isoforms to modulate signal transduction pathways involved in carcinogenesis including: 1) PPAR gamma, 2) fatty acid mediated regulation (e.g., COX-2, LOX, PPARs), 3) TGFb2 4) inflammation-mediated pathways including NFkB, 5) sphingolipid metabolism, 6) ER stress and 7) apoptosis in cell lines. We will be moving this research to the transgenic mouse model, TRAMP (TRansgenic Adenocarcinoma Mouse Prostate).
In addition to working with prostate and colon cancers, we have recently begun work in the area of leukemia and lymphomas. My lab has discovered that the vitamin E isoforms have ability to modulate expression of the homeobox domain genes which are perturbed in many leukemia and lymphomas.
Further, our work has extended from natural analogues of vitamin E to examining the effects of synthetic compounds of tocopherols and tocotrienols. The addition of various functional groups to some isoforms enhances anti-cancer activity; while addition of the same groups to other isoforms have little to no anti-cancer enhancement.
My collaborations include Dr. William Stone (Department of Pediatrics), Dr. Andreas Papas, Dr. Gus Papas, and Dr. John Hyatt (Yasoo Chemical), Dr. Julie Stimmel (Glaxo Smith Kline), Dr. Huda Salman (Washington University, St. Louis), Dr. Tamar Giorgadze (Wayne State University, Karmanos Cancer Institute) Dr. Laura Levy and Dr. Nakhle Saba (Tulane University, New Orleans) and Dr. Johnathan Wall (University of Tennessee, Knoxville). My lab has received funding from the East Tennessee State Research and Development Committee, the Cancer Research and Prevention Foundation, the Department of Defense and the American Institute for Cancer Research.
1. Investigation of the regulation of calcium and lipid membranes by vitamin E isoforms.
2. Investigation of the Acetylcholine Receptor modulation in the Brain.
3. Imaging techniques for the detection of prostate cancer.