Nancy Baenziger, Ph.D.

Associate Professor (Research) of Anatomy and Neurobiology

B.A. in Chemistry (1967)
St. Olaf College, Northfield, MN

Ph.D. in Biology (1971)
Washington University

Postdoctoral training (1971-1975)
Washington Univesity

BAENZIGN@WUSTL.EDU

Our research explores the molecular structures and the regulation of receptor systems for two multifunctional signaling molecules, bradykinin (BK) and histamine (HIS). These two "first messengers" serve to modulate the level of neuronal excitability mediating processes such as arousal, pain and irritant perception, thermoregulation, and control of blood flow. They play a role in inflammatory responses, regulate mitogenesis and protein synthesis, and link to the availability of growth regulators at both cell surface uptake transporters and intracellular phosphorylation pathways that transduce cell cycle regulation. We explore how cultured neuronal and other accessible cell types, including skin fibroblasts from patients with Alzheimer's disease, generate multiple forms of receptors for BK and HIS that are physiologically important. Our major interest is how expression and activity of these receptor systems can be turned up or down. They particularly tend to become turned up too much, causing tissue damage. Our studies define how intracellular signalling and second messenger pathways accomplish such modulatory steps. We determine what ligands and receptors see in each other, and how cellular flow of membrane components affects receptor regulation.

BK receptors mediate neuronal excitability, for example in processes such as cough reflexes and the pain and tissue remodeling that accompany injury and repair. We have shown that both neuronal cells and fibroblasts express the same cohort of multiple BK receptor forms that confer an extended or exaggerated profile of receptor activity. In Alzheimer's disease exaggerated signalling both acts through and is acted upon by specific protein kinase and phosphatase steps to miscue the post-translational processing of key proteins, so that their modifications cause accumulation in brain. The HIS receptor system interfaces with a Na+ and Cl-dependent transport process for amine compounds that can affect neurotransmitter sensitivities as well as growth regulation. Our studies of receptors that exert their actions both within and outside the nervous system seek to understand these receptor events both at the level of individual cells and of cell-cell interactions.

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