Research Topics
Department of Cell & Structural Biology and College of Medicine
Ph.D. (1977) Indiana University
Research Topics
Research Interests
We are interested in the role of neuropeptidergic systems in neuronal differentiation and brain development. Using both continuous (neuroblastoma) and non-continuous (primary cultures derived from fetal CNS) cell lines, our studies have largely focused on the brain angiotensin system, which is important in several brain related activities, including certain addictive behaviors and cardiovascular regulation, as well as development of the mammalian nervous system. We have previously reported on the de novo synthesis of the bioactive peptide in cultured brain cells and the signal transduction events involved in the release of the peptide from presynaptic nerve terminals. Characterization of membrane bound angiotensin receptors indicate that there are at least two subtypes: an angiotensin type 1 (AT1) receptor that is coupled to a G-protein (G) and participates in cardiovascular regulation; and an angiotensin type 2 (AT2) receptor that is not G-protein-coupled and appears to be involved in the up-regulation of immediate early genes and neuronal differentiation.
A second line of investigation involves the pharmacological manipulation of the brain-renin-angiotensin system as a mechanism to delay or block the development of neurogenic hypertension. These studies include investigations into the efficacy of angiotensin-converting enzyme inhibitors (e.g., captopril) to penetrate brain tissue and block the generation of angiotensin II, and peptide and nonpeptide receptor antagonists to block the physiological effect of the endogenous peptide. We are also studying mechanisms of signal transduction following activation of the brain angiotensin receptor in an effort to identify other possible sites for pharmacological intervention.
The potential applications of this research include: (1) the development of new CNS-acting pharmacological agents that may be useful in a number of brain related disorders (i.e., neurogenic hypertension) for the treatment of hypertensive disease; (2) the use of cultured neoplastic and non-neoplastic brain cells for the study of brain chemistry, physiology, and pharmacology; and (3) the identification of pharmacological probes that can be used to characterize membrane bound protein receptors.
Key Words DNA-Protein Interactions, Lymphokines/Growth Factors, Disease
Models, Hormones, Animal Cell and/or Tissue Culture, Neurobiology, Protein Purification
and Characterization, Protein Processing and Secretion, Active Sites and Receptors
Current Research Funding
American Heart Association