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Current Research Projects
Patricia E. Molina - Department Head
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.
Research interests in our laboratory center around the investigation of neurobiological changes associated with altered motivational systems in drug and alcohol dependence. Our research strategy is to first determine alterations in neuronal signaling following excessive drug or alcohol use, and then to investigate which neuroadaptations are most critically involved in driving excessive drug intake. A closely associated goal is to understand signaling changes induced by re-exposure to drug- or stress-paired contexts and how these processes may contribute to relapse and other motivational disorders. Finally, our most recent focus is on the interaction of addiction and chronic pain. Employing animal models of these conditions, we are currently investigating how persistent inflammatory pain alters central reinforcement circuitry and motivated behavior.
Our studies primarily measure protein- and phosphoprotein-level neuroadaptations in brain centers responsible for the establishment and maintenance of the addicted state. We are able to manipulate molecular targets within specific brain regions through a variety of technologies, including viral-mediated gene overexpression and knockdown strategies. These projects involve close collaboration with distinguished LSUHSC and national investigators.
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:
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.
Nicholas W. Gilpin
My lab utilizes animal models to identify the underlying neurobiological mechanisms of alcohol dependence and stress disorders. We work to understand the neuropharmacology of drug reinforcement in the drug-dependent organism, and we are also interested in examining the neurobiological mechanisms of co-dependence on more than one drug. To answer these questions, we use techniques that include operant drug self-administration, acoustic startle reflex, tests of pain and mechanosensitivity, tests of anxiety-like behavior and locomotor activity, alcohol and nicotine vapor inhalation for induction of physical dependence, behavioral pharmacology, immunohistochemistry, and Western blots.
Lisa M. Harrison-Bernard
Our research focuses on how the effects of two important hormonal systems, renin-angiotensin and endothelin, contribute to the failure of normal kidney blood vessel function and lead to the development and progression of kidney disease in type II diabetic patients. The research is focused on determining the role of intrarenal production of angiotensin and endothelin-1 via chymase-dependent pathways to the microvascular and glomerular dysfunction contributing to the progression of diabetic kidney disease. In vivo and in vitro experimental techniques are performed in control and type II diabetic mice
Barry J. Potter
The generation of free radicals is a consequence of both normal biologic processes & pathophysiologic disease processes. At low concentrations, they frequently function as signaling entities, but a high levels compound deleterious events. In particular, reactive oxygen species (ROS) are usually produced following tissue injury & may exacerbate that insult. As a result of continuous chronic free radical production, the normal cellular anti-oxidant mechanisms may be overwhelmed, leading to cellular & ultimately systemic oxidative stress. It is well known that oxidative stress plays a role in many diseases. In particular, it has been implicated in the pathophysiology of liver injury during xenobiotic and alcohol metabolism, cardiovascular ischemia/reperfusion injury, and activated phagocytic cell attack . Another consequence of chronic ROS production is the change in cellular redox potential, as evidenced either by changes in NADPH/NADP+ or GSH/GSSG ratios. Current research in my laboratory focuses on measurement of reactive free radicals, oxidative stress, antioxidant capacity & redox changes in cardiovascular, nutritional & alcohol-related diseases. Determinations are made in vivo or ex-vitro biological material using Electron Paramagnetic Resonance (EPR) techniques using paramagnetic spin traps or spin probes. Antioxidant capacity is determined by changes in stress-related free radical determination in the presence or absence of cellular recycling.
Research in our laboratory focuses on understanding the mechanisms that regulate proliferation and differentiation of stem cells. We are specifically interested in dysregulation of skeletal muscle stem cell (satellite cells) signaling that alters the fate of these cells. Using a model of chronic alcohol and Simian Immunodeficiency Virus (SIV) infection, we are studying the molecular mechanisms of impaired differentiation of satellite cells contributing to muscle wasting. Currently we are investigating two possible mechanisms. 1. Does a chronic proinflammatory and prooxidative skeletal muscle milieu inhibit myogenesis and promote a profibrotic phenotype of satellite cells. 2. Does an altered skeletal muscle milieu induce epigenetic alterations in satellite cells leading to impaired myogenesis? Our laboratory utilizes in vivo approaches, cell culture systems and molecular biology techniques.
Research in the Yue laboratory focuses on understanding the pathophysiology and molecular mechanisms of pulmonary fibrosis. Specifically we are investigating the role of heparan sulfate (HS) 6-O-sulfation in the development of idiopathic pulmonary fibrosis (IPF), a debilitating and often fatal illness for which there is no FDA-approved therapies. Structurally HS is similar to the anticoagulant heparin. In contrast to heparin which is a special product of tissue mast cells, HS is expressed virtually by all mammalian cells and involved in the regulation of a multitude of physiological and pathological processes. Combining in vivo fibrosis studies using genetically modified mice and in vitro cell signaling, we are investigating the role of HS 6-O-sulfation in multiple signaling pathways active in IPF, including TGF-b1, Wnt and FGF signaling pathways. Our findings could lead to the development of novel therapies for IPF.
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 Sciences Research Building. The department uses additional space in the School of Dentistry.