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CHRISTINA VOELKEL-JOHNSON, Ph.D.
Assistant Professor, MUSC, Microbiology and Immunology
DEGREES
Ph.D., 1995, Immunology, North Carolina State University
M.S., 1992, Microbiology, North Carolina State University
B.S., 1989, Biology, Fayetteville State University
RESEARCH INTERESTS
Tissue homeostasis is a balance between life (cell growth) and death (apoptosis). When this balance is lost, uncontrolled cell growth leads to cancer and threatens the organism. In my laboratory we seek to understand the apoptotic process and to use this knowledge to develop novel treatment strategies against cancer.
Current research is focused on a protein called TRAIL (tumor necrosis factor-related apoptosis inducing ligand). TRAIL induces apoptosis via death receptors on the cell surface. Initial studies suggested that TRAIL selectively induces apoptosis in malignant cells. However, more recently it has been shown that many cancer cells actively resist TRAIL-mediated apoptosis. We found that resistance to soluble TRAIL can be overcome by combination with the chemotherapeutic agent doxorubicin or by an adenovirus that expresses full-length membrane bound TRAIL (AdTRAIL). Unfortunately, sensitization by either mechanism is not selective for malignant cells. In prostate cells selectivity can be achieved by utilizing an antibody to the TRAIL receptor DR4 in combination with doxorubicin. Doxorubicin appears to sensitize cells to TRAIL by downregulating the anti-apoptotic protein called c-FLIP. Therefore, regulation of c-FLIP is one current focus of our research. We are also studying why AdTRAIL can induce apoptosis in cells that are resistant to soluble TRAIL.Translational studies include the treatment of prostate cancer with combination therapy and treatment of bladder cancer using intravesical gene therapy.
In addition, we are investigating the role of ceramide in TRAIL-mediated apoptosis. Ceramide is a metabolite of sphingolipid metabolism that is involved in numerous physiological responses, including apoptosis. In the colon, ceramide levels are reduced in malignant tissue compared to the normal mucosa. Treatment with ceramidase inhibitors, which should restore ceramide levels, can prevent or eliminate liver metastases in a mouse model. Ceramide has also been shown to overcome resistance to FasL, a death ligand similar to TRAIL. We believe that defective ceramide signaling may be responsible for resistance to TRAIL. This project is supported by the Center for Colon Cancer Research at the University of South Carolina.
CONTACT INFORMATION
Medical University of South Carolina
Department of Microbiology and Immunology (BSB 221 A)
171 Ashley Avenue
Charleston, SC 29425
E-mail
Office: 843 . 792 . 3125 | Lab: 843 . 792 . 3156 | Fax: 843 . 792 . 2464
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