Steven Hinrichs, M.D.
Interests:
Molecular Therapeutics for Cancer
Animal Models of Molecular Disease Mechanisms
Infectious Diseases
Informatics and Electronic Information Systems
Chair
Professor
Director of Microbiology and Virology
Director, Nebraska Public Health Laboratory
Research:
My academic research activities are centered in two areas, including cancer biology and infectious diseases. The research activities have considerable overlap when studied at the molecular level and provide the opportunity for insights into many issues of clinical relevance. I am interested in how infectious diseases and viruses in particular are involved in the development of the neoplastic process or complicate its treatment. We have developed a model system for inhibiting the transcriptional activation process resulting from infection by HTLV-1 whereby the Tax protein up-regulates expression of a variety of other genes through a cyclic AMP responsive element. We identified a monoclonal antibody that blocks the binding of ATF-1 to DNA with an accompanying decrease in transcriptional activation. The complementarity determining regions of this antibody have been cloned into a functional scFv that can be expressed in cells. The relevance of this approach comes with the knowledge that many characteristic chromosomal translocations incorporate the transcriptional activation domain of one gene and the DNA binding domain of a second gene. We have shown that one example of such a fusion gene is overexpressed and is critical for the maintenance of proliferation in a sarcoma. We are now using x-ray crystallography to examine the interactions between the CDRs of the antibody and its epitope to gain more insight into key molecular interactions and possible future developments of carbon-based inhibitory molecules.
The second aspects of cancer and infectious diseases relates to the complications of treatment of patients who are immunosuppressed. One of the most insidious infections is that by molds and fungi which reside in the environment and present minimal threat to immunocompetent individuals. We have developed novel molecular detection strategies that can also be used to identify the specific fungus at the species level in blood and/or tissue. These efforts have been recently expanded to successfully identify all known pathogenic and opportunistic fungi.
Education and Training
B.S., University of North Dakota, 1976 (Honors)
M.D., University of North Dakota, 1980
Residency, University of California, Davis, 1980-1984
Board Certified in Anatomical and Clinical Pathology
Medical Staff Fellow, NIH, 1985-1987
National Activities
CDC - NEDSS Advisory Board
APHL - Chair, Management Information Systems Committee
Member - California Cancer Research Committee
Editorial Boards or Journal Reviewer - Journal of Biological Medicine, JASCP, Archives of Pathology
