Curt D. Sigmund, Ph.D.

Professor of Medicine and Molecular Physiology & Biophysics

State University of New York at Buffalo, 1987

Research Interests

Title: Molecular Genetics and Molecular Biology of the Renin-Angiotensin System
My laboratory is primarily interested in investigating the regulation of genes involved in cardiovascular homeostasis and in creating new transgenic and knockout models of cardiovascular disease. We are currently investigating the mechanisms regulating the expression of the renin gene using state-of-the-art molecular approaches including transfection analysis, use of dominant-negative transcription factors, identification and cloning of transcription factors, assessing protein-DNA and protein-protein interactions and by using transgenic mice. Using these approaches, we have identified an enhancer of transcription, mapped the location of transcription factor binding sites, and identified some of the transcription factors involved in regulating the renin gene. We are currently generating mutations in some of these binding sites using transgenic and knockout mice to assess their importance in vivo. We also are using gene targeting techniques in embryonic stem cells to create null mutations in genes controlling cardiovascular function, and are using novel methods to control both the spatial and temporal expression of genes in transgenic mice including, tissue-specific promoters, inducible/repressible promoters, and the cre-loxP system to create tissue-specific knockouts. We have developed several transgenic models of human cardiovascular disease and are currently performing knockouts and tissue-specific knockouts of genes controlling cardiovascular function.

Selected Publications

1. Keen, H.L., Ryan, M.J., Beyer, A., Mathur, S., Scheetz, T.E., Gackle, B.D., Faraci, F.M., Casavant, T.L., Sigmund, C.D. Gene Expression Profiling of Potential PPAR? Target Genes in Mouse Aorta Physiological Genomics. 18: 33-42, 2004.

2. Sakai, K., Chapleau, M.W., Morimoto, S., Cassell, M.D. and Sigmund, C.D. Differential Modulation of Baroreflex Control of Heart Rate by Neuron- vs. Glia-derived Angiotensin II. Physiological Genomics 20: 66-72, 2004.

3. Sherrod, M., Liu, X., Zhang, X., and Sigmund, C.D.: Nuclear Localization of Angiotensinogen in Astrocytes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288:R539-R546, 2005.