One of the mainstays of research in the Department of Physiology at MCW is its National Institutes of Health-sponsored Program for Genetics Application entitled Physiogenomics of Stressors in Derived Consomic Rats & Knock-Out Rats for Physiological Genomics.
This PGA is focused on understanding the genetic basis of fundamental mechanistic pathways of the heart, lung, kidney, blood and vasculature through development of consomic rat panels and knockout models and physiological genomics, using environmental stressors. The dissemination of PhysGen data, animals, tissue slides, and bioinformatics resources to a large number of investigators is providing a valuable new tool to allow the linkage of genetic sequence information for the identification of gene function and the genetic basis of complex diseases.
Program Project Grants (PPGs)
The Program Project Grant in the department of Physiology is entitled Blood Pressure – Determinants & Controllers (funded by National Institutes of Health/National Heart Lung and Blood Institute grant 5 P01 HL29587-22, Allen J. Cowley, Jr., Principal Investigator). Ongoing for many years, this project was designed to explore the renal and vascular mechanisms involved in the long-term control of arterial pressure. We are currently focused on the interactions of the three important controllers of renal and peripheral vascular tone and arterial pressure: nitric oxide, 20-HETE and angiotensin II.
Part of what makes this program so strong is its position within a cluster of powerful, ongoing research programs supported by the within the department. Some of the most recent include:
Knock-out Rats for Physiological Genomics
(NIH/NHLBI grant 5 U01 HL66579-05, Howard J. Jacob, Principal Investigator)
The major goals of this project are to develop, phenotype, and distribute 56 consomic strains in the form of reciprocal chromosomal substitutions.
SCOR-Molecular Genetics of Hypertension
(NIH/NHLBI grant 5 P50 HL54998-09, Allen J. Cowley, Jr., Principal Investigator)
This project's goal is to determine the genetic loci and specific genes whose expression results in hypertension and in important phenotypic changes associated with hypertension.
P450 Eicosanoids and Altered Renal Function
(NIH/NHLBI grant 2 R01 HL36279-18, Richard J. Roman, Principal Investigator)
To study the role of the diminished production of 20-HETE in the thick ascending limb of Henle C1 - transport and in the development of hypertension in Dahl rats.
Physiological Genomics of Hypertensive Renal Disease
(NIH/NHLBI grant 1-R01 HL69321-02, Howard J. Jacob, Principal Investigator)
The major goal of this project is to define the genes on chromosome 1 responsible for the development of proteinuria and glomerular disease in Fawn-Hooded rats.
Mechanisms Regulating Nutritive Cerebral Blood Flow
(NIH/NHLBI grant 1-PO1 HL59996-05, David R. Harder, Principal Investigator)
Project 2: NO-20-HETE Interaction in the Control of Cerebral Vascular Tone
Core B: Biochemical and Molecular Core. This project was designed to study the role of 20-HETE in mediating the effects of nitric oxide on cerebral vascular tone.