Sharon Campbell, Ph.D

Campbell

 

 

 

Sharon Campbell, Ph.D.     
Assistant Professor, Department of Biomedical Sciences
Curriculum Vitae

Contact Information:

Deparment of Biomedical Sciences
James H. Quillen Collge of Medicine
PO Box 70582
Room A027 Stanton Gerber Hall (Bldg. 178)
VA Medical Center 
Phone: (423) 439-2266
Fax: (423) 439-2030 
E-mail     


Education:

1992 – B.S., Chemistry, East Tennessee State University, Johnson City, TN

2001 – Ph.D., Biochemistry, James H. Quillen College of Medicine, Johnson City, TN


Research/Teaching Interests:

1.     Dietary constituents and disease prevention


Research Interests:

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. 



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Structure of Vitamin E Isoforms

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 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.    

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. Greg Ordway (Department of Biomedical Sciences), Dr. Russ Brown (Department of Psychology) Dr. William Stone (Department of Pediatrics), Dr. Koyamangalath Krishnan(Department of Internal Medicine), Dr. Victoria Ramsauer (Bill Gatton College of Pharmacy), Dr. Stacy Brown (Bill Gatton College of Pharmacy), Dr. Julie Stimmel (Glaxo Smith Kline), and Dr. Tamar Giorgadze (Wayne State University, Karmanos Cancer Institute) 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.


Future Research Interests:   

1. Examining the effects of Vitamin E isoforms on Depression and Diabetes.

2. Examining ROS in the brain of stressed rats using the social defeat stress model.


Lab Member:

Aashish Morani


Selected Publications:

[1]      Stone WL, Krishnan K, Campbell SE, Palau VE. The role of antioxidants and pro-oxidants in colon cancer. World J Gastrointest Oncol 2014;6:55–66.

[2]      Campbell, Sharon E., Morani A, Stone W, Krishnan K, Palau V. Vitamin E Isoforms: Multiple Mechanisms of Action against Carcinogenesis. In: Free Radicals: The Role of Antioxidants and Pro-oxidants in Cancer Development. 1st ed. Nova Science Publishers; 2014.

[3]      Stone W, Campbell S, Krishnan K. The Role of Vitamin E in Prostate Cancer. In: Oxidative Stress in Cancer Biology and Therapy,. Humana Press; 2012. p. 333–356.

[4]      Shin-Kang S, Ramsauer VP, Lightner J, Chakraborty K, Stone W, Campbell S, Reddy SA, Krishnan K. Tocotrienols inhibit AKT and ERK activation and suppress pancreatic cancer cell proliferation by suppressing the ErbB2 pathway. Free RadicBiolMed 2011;51:1164–1174.

[5]      Campbell SE, Rudder B, Phillips RB, Whaley SG, Stimmel JB, Leesnitzer LM, Lightner J, Dessus-Babus S, Duffourc M, Stone WL, Menter DG, Newman RA, Yang P, Aggarwal BB, Krishnan K. gamma-Tocotrienol induces growth arrest through a novel pathway with TGFbeta2 in prostate cancer. Free RadicBiolMed 2011;50:1344–1354.

[6]      Campbell SE, Musich PR, Whaley SG, Stimmel JB, Leesnitzer LM, Dessus-Babus S, Duffourc M, Stone W, Newman RA, Yang P, Krishnan K. Gamma Tocopherol Upregulates the Expression of 15-S-HETE and Induces Growth Arrest Through a PPAR Gamma-Dependent Mechanism in PC-3 Human Prostate Cancer Cells. Nutr Cancer 2009;61:649–662.

[7]      Stone W, Ramsauer V, Campbell S, Krishnan K. Targeted Prostate Cancer Chemoprevention Trial with Tocotrienols. In: Tocotrienols Vitamin E Beyond Tocopherols,. 2nd ed. CRC Press,; 2008.

[8]      Campbell SE, Whaley SG, Phillips RB, Aggarwal BB, Stimmel JB, Leesnitzer LM, Blanchard SG, Stone WL, Muenyi C, Krishnan K. Gamma tocotrienol and prostate cancer: The regulation of two independent pathways to potentiate cell growth inhibition and apoptosis. Journal of Oil Palm Research 2008;October 2008:33–43.