Physiology Research

The MCW Cardiovascular Center, directed by Ivor Benjamin, MD, FAHA, FACC, translates biological science into clinical applications for care and treatment of patients. CVC physicians serve patients with heart and vascular diseases at Froedtert Hospital, Children's Wisconsin, the Clement J. Zablocki VA Medical Center and other regional facilities.

CVC researchers, working in one of the largest laboratory complexes in the U.S., have made significant accomplishments toward understanding and preventing diseases such as stroke, atherosclerosis, hypertension, and diabetes. The National Institutes of Health named the MCW CVC a Specialized Center for Research on Hypertension, one of only five in the U.S. Established in 1992, the Cardiovascular Center has more than 150 physicians and scientists from 23 departments at the Medical College of Wisconsin involved in multi-disciplinary research.

The Center of Systems Molecular Medicine at the Medical College of Wisconsin is directed by Mingyu Liang, MB, PhD, Eminent Scholar, Professor of Physiology. The mission of the CoSMM is to develop and apply systems molecular approaches to improve the understanding and treatment of human disease. The primary function of the CoSMM is to serve as an intellectual incubator for research and project development. The current areas of focus at the CoSMM are microRNA, epigenomics, and related translational research.

The Mellowes Center at MCW has its roots in the launch of the Human Genome Project and the 1999 founding of the MCW Human and Molecular Genetics Center. The Human and Molecular Genetics Center had the goal of developing and promoting genomic technologies and approaches and applying them to the study of genetic disorders. The plan called for developing the research expertise to capitalize on the remarkable progress of the Human Genome Project. Having the entire sequence of the human genome and several other model organisms and pathogens means that, in principle, for the first time scientists have a full compendium of genes related to health and disease. Over the next several decades, our scientists will focus on defining gene function (functional genomics) and how genes interact with each other and the environment to produce disease. The Mellowes Center is charged with developing the critical infrastructure needed to position the Medical College of Wisconsin as a leader in functional genomics. The investigators currently part of the Mellowes Center work in the areas of bioinformatics, genomics, high-throughput sequencing, and the development and use of single nucleotide polymorphisms (SNPs), expression analysis (microarray), and translational biology (transgenic and knock-out technologies).

The Marquette University and Medical College of Wisconsin Department of Biomedical Engineering is dedicated to the development and application of novel technologies in biomedical research.

It has five major areas of focus: proteomics, genomics, computational biology, molecular imaging, and technology development, each with an emphasis on the application and transfer of technology. One of the major goals is to help create productive interfaces and synergy between the various academic departments at MCW, other universities both within Wisconsin and nationally, and with the biotechnology and pharmaceutical industries.

At the General Clinical Research Center, the principles of science, need, and diversity converge to provide a foundation that facilitates research excellence and improves the health of diverse populations.

Founded in 1961, the General Clinical Research Center of the Medical College of Wisconsin is one of the first National Institutes of Health-sponsored GCRC sites. The MCW GCRC includes an Adult Center located in the Lower Level Pavilion at Froedtert Hospital and an outpatient Pediatric and Transfusion Medicine Satellite located in Children's Wisconsin.

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.

The MCW Proteomics Center is funded by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) to develop novel technologies for mass spectroscopy-based proteomic research. The project's goal is to enable quantitative analysis of the entire proteome (full complement of proteins expressed) of a single cell. This is a very technically challenging target and requires careful refinement at each step in the process, both experimental and computational. Through this refinement, we hope to dramatically increase the sensitivity, resolution and mass range of the analysis process to the point where single cell analysis is possible. The project includes a very strong group of collaborators in addition to MCW researchers, together creating a team of unique capabilities to take on this uniquely difficult problem.  

The Rat Genome Database is an online database that provides data and tools that support rat genomic research worldwide. RGD curates and integrates rat information published by members of the community, providing access via its website and unique analysis tools, all of which were developed to facilitate the use of the rat as a model system.