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.
Our 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 damaging effects of alcohol abuse on cardiac development and adult cardiac health,
- the cardiac effect of inhaled nicotine and cigarette smoke,
- the role of lysyl oxidase, a collagen crosslinking enzyme, and related peptides in adverse myocardial ECM remodeling, and
- sex differences in cardiac disease.
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/
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.
Research in my laboratory focuses on understanding the mechanisms leading to CD8+ T cell immunosenescence. We are currently examining the role of alcohol in the setting of HIV in promoting increased T cell activation and senescence, leading to precocious aging. Studies include examining how increased reactive oxygen species and mitochondrial damage lead to an immunosenescent phenotype. We have developed multiple flow cytometry based assays combined with downstream molecular analysis to examine these mechanisms.
Research in our laboratory focuses on mechanisms that regulate proliferation and differentiation of stem cells. Using animal models, we are studying epigenomic interactions that impair stem cell function contributing to dysregulated repair, regeneration and function. We are specifically interested in the dysregulation of skeletal muscle stem cell signaling that alters the fate of these cells in insults including alcohol use, HIV and disuse muscle atrophy. Our laboratory utilizes in vivo approaches, including models of alcohol administration and disuse atrophy; cell culture systems; and a wide array of molecular biology techniques to study genetic and epigenetic changes that contribute to dysfunction. Our ultimate goal is to develop epigenomic-targeted therapeutic and lifestyle interventions that improve muscle function and quality of life in aging or chronic diseases. The lab has also developed close collaborations within the department and at LSUHSC to investigate epigenomic mechanisms in metabolic dysregulation, and HIV disease.
The research interests of our laboratory are lymphatic vessel physiology and pathophysiological dyshomeostasis. We currently have two lines of research. The first one focuses on the effects of alcohol on lymphatic function and the immunocrosstalk between mesenteric lymphatic vessels (MLV) and perilymphatic adipose tissue (PLAT). Our approach is to investigate novel mechanisms involved in the development of adipose metabolic impairments and insulin resistance resulting from chronic alcohol consumption. Specifically, our studies examine how chronic alcohol disrupts visceral adipose immunity in response to MLV leakage. Our second line of research investigates the mechanisms underlying high fat diet and gonadal hormone loss-induced dysfunction of MLV and the metabolic consequences of lymph leakage into PLAT. These studies examine the epigenetic mechanisms involved in MLV dysfunction, in particular, microRNA-mediated alterations in tight junction protein expression and barrier function.
Research in my laboratory focuses on understanding the pathophysiology and molecular mechanisms of lung diseases. We have long-standing interests in the function of heparan sulfate 6-O-endosulfatases (the Sulfs) in the pathogenesis of acute lung injury, inflammation and fibrosis. In addition, a new direction of the lab is to examine the impact of chronic nicotine inhalation on the development of lung diseases and its associated molecular mechanisms.
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.