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Gregory
J. Bagby Research in my laboratory focuses on the physiology of the host defense system that protects us from bacterial and viral infections. We are especially interested in what happens to the host defense response to infection during immunocompromised states. Immunocompromised state that we primarily study is related to alcohol abuse because it is known to be an important risk factor for pneumonia. We study the host defense response to a wide variety of pathogens from bacterial infections of the lung to HIV infection. In our studies we use in vivo approaches as well as cell culture and molecular biology. Jerome W. Breslin The overall goal of my research is to discover and characterize the cellular and molecular mechanisms that regulate the cardiovascular system in health and disease. I am particularly interested in how the endothelial cells of exchange microvessels regulate transport of fluids and solutes between 1) the blood and tissues, and 2) the tissues and lymph. The microcirculation usually acts as a selective barrier, however, excessive leakage of plasma, also called microvascular hyperpermeability, occurs during shock or inflammatory disease processes and can lead to tissue dysfunction. On the lymphatic side, when lymphatic vessels fail to collect excessive fluids from the tissue, a debilitating condition known as lymphedema forms. The specific goals of my research are to better understand how inflammatory cells and mediators affect subcellular structures that control endothelial cell shape and adhesion, what genes promote microvascular hyperpermeability during disease processes, and what active role lymphatic endothelial cells may have in regulating lymph formation and propulsion. To achieve these research goals, I employ an integrative approach involving in vivo imaging experiments, cell culture models, and molecular biology techniques. Techniques routinely used in my lab include intravital fluorescence microscopy and image analysis, ECIS, protein analysis, and genetic mutation of cells. Recent studies have focused on the Rho/ROCK pathway in the control of endothelial cell tension development, the role of VEGFR-3 in lymphatic pump function, and how Toll-like receptor-4 contributes to systemic inflammation after severe burn injury. The intent of this research is to continually characterize the molecular and biochemical properties of adhesive and contractile structures that regulate microvascular permeability and lymph formation, with a practical view toward the development of therapeutic agents that target these end-point molecular processes, for more effective treatment of inflammatory diseases and lymphedema. Jason Gardner The major research emphasis is focused on understanding the pathogenesis of heart failure. Of particular interest are the mechanisms responsible for the adverse cardiac extracellular matrix (ECM) remodeling associated with the progression of congestive heart failure.
Current topics of study include: the role of lysyl oxidase, a collagen crosslinking enzyme, and related peptides in myocardial ECM remodeling, the cardioprotective effects of estrogenic pathways, including soybean- and plant-derived compounds, and the cardiac effects of inhaled particulate matter and cigarette smoke. Our laboratory utilizes rodent models of cardiac disease, including models of pressure overload and chronic ventricular volume overload. We also use primary adult cell culture to examine specific pathways involved in the remodeling process.
Lisa M.
Harrison-Bernard Research
focuses on the assessment of the functional and molecular mechanisms
linking the physiology of hypertension with the altered expression
of critical components of the renin angiotensin system - angiotensinogen,
angiotensin converting enzyme, renin, and the angiotensin type 1 receptor.
The role of the renin angiotensin system in controlling the renal
microvasculature tone is a specific area of research. The regulation
of both the function (vasoconstriction) and expression (mRNA and protein)
of the angiotensin receptor in the renal vasculature is performed
following chronic manipulation of circulating angiotensin II levels
in mouse gene knockout models for the two subtypes of the angiotensin
type one receptors, AT1A and AT1B. Another area of interest focuses
on understanding the intrinsic properties of the kidney which control
renal blood flow and glomerular filtration rate within a narrow range
during large fluctuations in arterial pressure. The rat and mouse
renal microcirculations are studied using the in vitro blood perfused
juxtamedullary nephron technique. This system allows the direct measurement
of vessel diameter single renal microvessels in both the cortical
and medullary circulations. Kathleen
H. McDonough Research in this laboratory
involves studying the effects of bacteremia (sepsis) and /or HIV-1
on myocardial function. We have shown that bacteremia causes myocardial
dysfunction and yet the heart develops mechanisms that protect it
from an ischemic challenge 1 day after the induction of sepsis. We
are investigating the proteins that may be involved in both the sepsis
induced dysfunction and the sepsis induced protection from ischemia
reperfusion injury. We are also investigating the mechanisms by which
HIV-1 can lead to cardiomyopathy by studying heart function in a transgenic
mouse that expresses one of the HIV-1 proteins, Tat. Studies utilize
the isolated perfused heart for determination of ventricular performance,
myocardial metabolism and inotropic responsiveness to catecholamines
and biochemical techniques to study changes in gene and protein expression.
Patrcia
E. Molina Current work
in my laboratory is focused on understanding the neuroendocrine mechanisms
involved in regulation of inflammatory responses to injury. In particular
the impact of alcohol on the outcome from traumatic injury as it pertains
to cardiovascular and host defense responses. Parallel studies address
the impact of chronic alcohol as it affects the course and progression
of AIDS-associated wasting. In addition, newly funded studies will
investigate the impact of cannabinoids on AIDS associated neurobehavioral,
immune and metabolic alterations. Johnny
R. Porter Our laboratory
conducts studies that are directed toward the understanding of neuroendocrine
mechanisms in the hypothalamus as they relate to caloric intake, body
weight regulation, and the pathophysiology of obesity. To achieve
these goals we study a genetic model of obesity. Techniques utilized
to accomplish our goals include behavior studies, techniques for drug
administration and implantation, high performance liquid chromatography
and in situ hybridization utilizing radiolabelled antisense olignucleotide
to detect specific mRNA activation. Our studies have focused on the
brain action of the neurosteroid DHEA and its interaction with monoaminergic
systems and the anorectic drugs. Recently we have begun studies on
interaction of cytokines and monoaminergic systems in the hypothalamus
We are specifically interested in determining the basal interaction
of these two systems in lean and obese (diabetic) rats in a situation
of inflammation. We predict that DHEA can reverse the pathological
consequences of inflammation by an action in the central nervous system. Barry J.
Potter The research
in this laboratory focuses on the mechanisms involved in the maintenance
of iron homeostasis and perturbations induced by such factors as infection
and alcohol abuse. Studies examine both the long-term effects on the
concentrations of iron in the various body iron pools and the kinetic
interactions between these pools. In addition, the superimposition
of iron deficiency (to mimic the anemic state) and iron loading (to
reflect hemochromatosis, siderosis and the thalassemias) are also
being investigated. Since all of these states are also seen clinically,
the long-term goal of this laboratory is to investigate the potential
benefits or adverse effects of alterations to iron homeostasis (such
as with chelation therapy, or iron administration) in the various
disease states. Research
Facilities Most of the
department’s faculty members occupy laboratories and offices
in the Medical Education Building, adjacent to the Health Sciences
Center Residence Hall. Faculty conducting research as investigators
of the NIAAA-supported Alcohol Research Center use laboratories in
the newly opened Clinical Research Sciences Research Building. The
department uses additional space in the School of Dentistry. |
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