Associate Professor (Research)
Anatomy and Neurobiology
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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.
Research Publications
Jong YJ, Ford SR, Seehra K, Malave VB, Baenziger NL (2003 Dec). Alzheimer's disease skin fibroblasts ively express a bradykinin signaling pathway mediating tau protein Ser phosphorylation. FASEB J. 17 (15): 2319-21. Full Article >
Jong YJ, Dalemar LR, Seehra K, Baenziger NL (2002 Dec). Bradykinin receptor modulation in cellular models of aging and Alzheimer's disease. Int Immunopharmacol. 2 (13-14): 1833-40. Full Article >
Jong YJ, Dalemar LR, Wilhelm B, Baenziger NL (1996 Jun). Human lung fibroblasts express multiple means for enhanced activity of bradykinin receptor pathways. Immunopharmacology. 33 (1-3): 9-15. Full Article >
Jong YJ, Dalemar LR, Wilhelm B, Baenziger NL (1996 Jun). Human lung fibroblasts express multiple means for enhanced activity of bradykinin receptor pathways. Immunopharmacology. 33 (1-3): 9-15. Full Article >
Dalemar LR, Ivy Jong YJ, Wilhelm B, Baenziger NL (1996 Mar). Protein kinases A and C rapidly modulate expression of human lung fibroblast B2 bradykinin receptor affinity forms. Eur J Cell Biol. 69 (3): 236-44. Full Article >
Baenziger NL, Mack P, Jong YJ, Dalemar LR, Perez N, Lindberg C, Wilhelm B, Haddock RC (1994 May 27). An environmentally regulated receptor for diamine oxidase modulates human endothelial cell/fibroblast histamine degradative uptake. J Biol Chem. 269 (21): 14892-8. Full Article >
Contact Info
Nancy Baenziger, Ph.D
Office Location: 957 McDonnell Sciences Bldg.
Office Phone: 314-362-2839
Campus Box: 8108
Fax: 314-362-3446
baenzign@pcg.wustl.edu
