Current Research Projects
Current work in our laboratory is focused on understanding the biomedical consequences of alcohol abuse on outcomes from traumatic injury and HIV infection. For additional information please visit our laboratory webpage: http://www.medschool.lsuhsc.edu/physiology/molina_lab/molinalab_research.aspx
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:
- 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.
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. For additional information please visit our laboratory webpage: http://www.gilpin-lab.com/
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
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.
The current research in my laboratory focuses on understanding peripheral and central mechanisms leading to obesity and related comorbidities. There are several projects in my laboratory investigating neural, behavioral and physiological factors affecting the susceptibility to developing obesity. These studies include the assessment of fat sensing via the oral cavity in obesity-prone and obesity-resistant rats and the assessment of inflammatory markers on the risk for cardiovascular disease in obesity-prone and resistant rats. We are also interested in the role of the hypothalamic neuropeptide, QRFP, on feeding and other motivated behaviors in male and female rats.
- Impact of chronic alcohol consumption on the disruption of bone marrow progenitor cell differentiation
- Effects of acute alcohol intoxication on the bone marrow response to bacteremia
- Understanding the role of ethanol in dysregulating DNA methylation patterns, and the physiologic outcome of these perturbations
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.
The Department has state of the art research equipment including facilities and instrumentation for cell and tissue culture; RT PCR, DNA and RNA isolation, and in situ hybridization; gas and high pressure liquid chromatography; fast protein liquid chromatography; flow cytometry; and electron paramagnetic resonance spectroscopy. The Health Sciences Center Core Laboratories contain facilities for oligonucleotide synthesis, peptide synthesis and microsequencing, antibody production, mass spectroscopy, fluorescence-activated cell sorting, and phosphorimaging. An Image Analysis facility includes a confocal microscope as well a molecular modeling workstation.
The Physiology Graduate Student Office is equipped with several personal computers for student use with full access to the Internet and a range of software for scientific research applications.