Keith A. Crist, Ph.D.
University of Toledo College of Medicine
Health Sciences Campus
Health Education, Rm. 205A
3055 Arlington Ave.
Toledo, Oh 43614-5806
Department of Food Science and Human Nutrition
Michigan State University
Research - Molecular Carcinogenesis.
Alterations in gene expression related to tumorigenesis and response to chemotherapy.
Research/Scholarly Activities Chemoprevention: Chemotherapy; DNA library screening, alterations in gene expression, apoptosis.
Dr. Crist's laboratory is pursuing two major interests:1) identifying early alterations of gene expression related to breast cancer development; and 2) improving the effectiveness of TNF-a mediated induction of programmed cell death in chemotherapeutic treatment of pancreatic cancer.
Several methodologies have recently been developed which allow demonstration of expression differences between tumor and normal tissue without prior understanding of what those differences might be. This allows identification of previously unknown genes or unknown functions of known genes related to carcinogenesis. In general these methods are preferentially suited to identification of suppressor genes, whose growth regulatory function is lost from the tumor. We are using cDNA library screening, which allows identification of both increases in gene expression as well as loss, in the rat mammary gland as a model system. Alterations identified at the adenocarcinoma stage can be used to screen earlier stages of neoplasia, as well as tumors of different tissue types to identify common changes.
Programmed cell death, or apoptosis, is a normal response to a variety of conditions including DNA damage. Neoplastic cells, which increase in the extent of their genetic abnormality, must inactivate this pathway to accomplish unrestrained tumor growth. TNF-a activates a cell surface receptor that recruits the cooperative binding of several intracellular proteins including those directing activation of apoptosis. Therapeutic levels of TNF-a administered systemically are associated with significant toxicity. Dr. Crist's laboratory is studying effectors of these signaling pathways that promote induction of apoptosis, increasing TNF-a therapeutic effectiveness.
Braun DP,.Crist KA, Shaheen F, Staren ED, Andrews S, Parker J. (2005) Aromatase inhibitors increase the sensitivity of human tumor cells to monocyte-mediated, antibody-dependent cellular cytotoxicity. Amer J Surg 190:570-1
Crist KA, Zhang Z, You M, Gunning WT, Conran PB, Steele VE, Lubet RA. (2005) Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture. Carcinogenesis. 26:951-7