Current Research

Dr. Benson Akingbemi.  Role of Estrogen, the ER, and Growth Factor Receptors in Mediating the Effects of Environmental Stressors in Leydig Cells. The laboratory has interests in male reproductive biology and toxicology.  There is evidence that excessive exposure of the male reproductive tract to estrogen and estrogen receptor (ER) agonists and antagonists exert detrimental effects on tissue function.  Thus, there is growing public concern that chemicals in the environment (food, air, water), which have estrogenic properties, may cause adverse effects on male reproductive health.  These compounds, which are designated xenoestrogens or endocrine disruptors, impact the endocrine profile by acting through steroid hormone receptors.  However, estrogenic signals are also mediated in part by growth factor receptors (e.g., epidermal growth factor and insulin growth factor-1 receptors, EGFR and IGF-1R).  Studies in our laboratory are designed to investigate the role of estrogen, the ER, and growth factor receptors in mediating the effects of environmental stressors in Leydig cells and disrupt the endocrine function of the testis. 

Dr. Dawn Boothe:  Resistance and Virulence in Canine and Feline Eschericia coli Pathogens. We have a number of ongoing projects related to characterizing molecular mechanisms of resistance, particularly to fluoroquinolones but also beta-lactams. Mechanisms of resistance to fluoroquinolones focus (not exclusively) on efflux pumps and their regulators. Activities focus on a library of 3000 isolates recently collected from dogs and cats throughout the USA. Most recently, we have begun to investigate virulence factors in the isolates, and hope to identify isolates associated with asymptomatic bacteruria as well as describe the incidence of the ST131 strain, a strain characterized by both virulence and resistance. Our activities include a focus on the relationship between virulence and resistance, both in chromosomal and mobile DNA.  Through this library of isolates, we are also  epidemiologically describing risk factors associated with emergent antimicrobial resistance in dogs and cats.  Drug Metabolism in the Horse. The broad subject indicates the early stage of this focus of research  which will involve tissue slice methodology and histologic and  molecular techniques to characterize drug metabolism at the tissue (liver and intestines) level under  normal conditions and in response to changes induced by analgesic drugs, including but not limited to  non-steroidal anti-inflammatory drugs. Studies involving cytochrome P450 as well as selected transport proteins are in the early stages of formulation. These in vitro and ex vivo studies will be supported by a clinical trial in adult horses which will compared the kinetics of a compounded versus commercial preparation of firocoxib.

Dr. Pete W. Christopherson and Dr. Mary K. Boudreaux:   Inherited Diseases of Platelets. Our laboratory is involved with evaluating inherited platelet disorders in dogs, horses, and cows at the functional, biochemical, and molecular level. Students working in my laboratory would have exposure to a broad array of experiences ranging from blood collection, platelet isolation, platelet function testing, DNA isolation, PCR techniques, and flow cytometry.

Dr. Chad D. Foradori:  Neuroendocrine Responses to Herbicide Exposure. The nervous system mediates all aspects of hormone regulation either by direct innervation of target organs or via the circulatory system and pituitary function. The hormonal milieu, in turn, feeds back onto the nerve system controlling multiple functions including necrosis, neurogenesis, plasticity, behaviors and, of course, future hormone release. My laboratory studies the regulation of reproductive and stress hormones by the brain.  One way to identify the underlying mechanisms involved in the normal control of a system is to examine it during periods of distress or after insults. Therefore, we examine the effects of a common herbicide found in the environment, atrazine, on neuroendocrine function. Atrazine has been shown to inhibit the normal neuroendocrine function leading to puberty, ovarian cyclicity and ovulation. At the same time, atrazine has been found to stimulate the release of stress hormones. Studies conducted in the Summer of 2012 will be focused on 1) determining the effects of long-term atrazine exposure on adrenal steroidogenesis and liver xenobiotic metabolism and 2) examining the possible linkage between atrazine effects on the reproductive and stress axes. The prospective student will be exposed to a number of techniques including immunohistochemistry, confocal microscopy, real-time polymerase chain reaction, western blotting, ELISAs, rodent handling and care.

Dr. Reid Hanson and Dr. Robert Jackson: A Study of the Visco-elastic and Friction Profiles of Equine Cartilage Surfaces. Our lab seeks to characterize and compare the material properties of cartilage located within various joints of the equine limb.  Specifically, we will investigate the visco-elastic stiffness and friction coefficient of the biphasic cartilage structure.  These biphasic properties affect the performance of the joint as it carries different loads and motions. This study is to determine if different types of joints with different ranges of motion possess different material properties best suited for the joint’s individual conditions. Analyzing the various cartilage surfaces within each joint and between joints will lead to a better understanding of the mechanisms controlling the performance of healthy joints in horses and humans. This data will be used to translate into the design of better artificial joints.

Articular cartilage samples will be extracted from a recently deceased horse and analyzed in the Multiscale Tribology Laboratory in Mechanical Engineering. The tests will be performed using a CETR-UMT-3 high load heavy duty tribometer which is capable of performed indentation tests on the cartilage and rotating friction tests. The indentation tests will measure stiffness by recording the force versus displacement curves of a punch as it is pressed into the cartilage.  The friction coefficient of cartilage samples will be measured by either sliding a sample of cartilage against a metal probe or against another sample of cartilage, while recording normal and tangential forces.  In addition, a Veeco Dektak 150 Stylus Surface Profilometer fitted with the N-Lite Low Force package and 3-D mapping option will be used to measure the surface roughness of the cartilage to the nanoscale level.

Dr. Michael H. Irwin and Dr. Carl A. Pinkert:  Genetic Engineering of Animals. Ongoing studies revolve around innovative approaches toward manipulation of mitochondrial genetics in mice, swine and cattle. Using gene transfer techniques targeting the mitochondrial DNA (mtDNA) genome, we are developing genetically modified animal models of: 1) increased production efficiency – harnessing mitochondrial genetics to enhance metabolic and production performance and 2) severely debilitating (and often lethal) human disorders caused by genetic mutations that affect mitochondrial function. Our genetically altered animal models will be used to provide a greater understanding of mitochondrial dynamics and pave the way for a host of basic and translational technologies including targeted gene therapies. Possible summer projects will focus on: 1) animal characterizations, 2) developing molecular/cloning skills and 3) participating in the creation of engineered laboratory and domestic animal models.

Dr. Robert Judd: Regulation of Adipokine Trafficking and Secretion. Adipokines are proteins secreted primarily by adipose tissue and have been shown to regulate energy metabolism and consumption. Over the past 7 years, we have been particularly interested in the physiological role and regulation of the adipokines resistin, leptin and adiponectin. Adiponectin has insulin sensitizing and anti-atherogenic properties which make it an excellent marker of the metabolic syndrome and cardiovascular disease. However, little is known about the factors which regulate adiponectin synthesis and secretion. Recent investigations from our laboratory suggest that a novel G-protein coupled receptor for niacin (vitamin B3) (GPR109A) decreases lipolysis and increases adiponectin secretion from adipocytes in a coordinated fashion. Other studies from our laboratory and others have shown the involvement of other G-protein coupled receptors in the modulation of lipolysis. However, there is no information regarding the regulation of adiponectin secretion. Studies conducted in the Summer of 2012 will be focused on identifying the downstream intermediates that are required for adiponectin secretion from the GPR109A receptor and other G-protein coupled receptors. The results of these studies will provide important information regarding the regulation and secretion of adiponectin and could lead to the development of pharmacological and molecular biology strategies to regulate lipolysis and adiponectin secretion. The prospective student will be exposed to a number of adipocyte cell and molecular biology techniques including: 3T3-L1 and primary adipocyte cell culture, rodent handling and care, electron microscopy, confocal microscopy, real-time polymerase chain reaction, western blotting and ELISAs.

Dr. Mahmoud Mansour :  Effect of Orlistat and Fatty Acid Synthase Inhibitors on Cellular Activity of Fatty Acid Synthase in DU 145 cells.  Prostate cancer (PCa) is a leading cause of cancer deaths among men in the United States and is the second leading cause of cancer death in all men. Research in my laboratory is using human PCa cell models to investigate novel combination therapy for treatment of PCa.  We utilize tools of molecular and cell biology, chemistry and radiochemistry to determine the cytotoxic efficacy of selected peptides, plant extracts and other molecular agents on normal and PCa cells. Interested students will have the opportunity to learn an array of techniques that help them explore a hypothesis that could lead to better understanding of growth regulation in PCa.

Dr. Douglas Martin:  Neurological Disease Gene Therapy and/or Small Molecule Therapy. The laboratory’s model of neurodegenerative disease is feline gangliosidosis, a disorder in which abnormal functioning of lysosomes causes progressive nervous system dysfunction and death. Children affected by gangliosidosis die by 5 years of age because no effective treatment is available. However, new gene therapy strategies have been tested in mouse models of gangliosidosis with excellent results. Before inclusion in human clinical trials, new therapies are tested in the feline model for safety and therapeutic benefit. The laboratory employs a variety of experimental techniques, ranging from intracranial injection of therapeutic agents to biochemical and molecular biological evaluation of therapeutic effectiveness. Students may participate in both experimental procedures and laboratory research. This work is part of an international effort of collaborative scientists and physicians, the Tay-Sachs Gene Therapy Consortium, whose goal is to begin gene therapy clinical trials in humans.

Dr. Amelia Munsterman and Dr. Reid Hanson:  Epidemiology and Risk Factors for Colic in Horses.  Colic is a common intestinal disorder that affects horses evaluated on emergency by the equine veterinarian.  Our goal is to further identify common risk factors that may contribute to colic, as well as evaluate laboratory data and physical exam findings to determine any affect on prognosis and outcome.  Students working with us will have the opportunity to assist us in gathering epidemiologic and patient information to add to the growing data base on colic at Auburn.  In addition, we plan to obtain feed samples to help link specific types of colic to the intake of specific nutrients, or lack thereof.  As part of this research, students will be able to participate in examination and treatment of horses suffering from colic. 

 Dr. Satyanrayana Pondogula:  Role of Pregnane Xenobiotic Receptor in the Pathogenesis and Therapeutic Response of Canine Mammary Tumors and Osteosarcoma .  Pregnane xenobiotic receptor (PXR) is an orphan nuclear receptor and is promiscuous and unique in that it is activated by a diverse group of xenochemicals, including therapeutic drugs and environmental carcinogens. PXR has emerging implications in cancer cell growth and/or drug resistance of many human cancers, including breast cancer and osteosarcoma. Dogs with mammary tumors and osteosarcoma provide important models for the same cancers in humans. The studies will be designed to investigate the role of PXR in the progression and therapeutic response of canine mammary tumors and osteosarcoma. The prospective students would have exposure to cell and molecular biology as well as biochemical approaches.

Dr. Dean Schwartz:  Role of Oxidative Stress in the Progression of Cardiovascular Disease.  Oxidative stress is a contributing factor to the progression of many disorders and is at the forefront of research in cardiovascular disease.  Several enzymes have been reported to contribute to the production of ROS including NADPH oxidase (NOX).  NOX is a membrane bound, multisubunit enzyme that transports electrons across biological membranes to molecular oxygen to catalyze the formation of superoxide. A major focus of our lab is examining the role of NOX in the development of complications associated with diabetes and equine laminitis.  Students involved in this project will be exposed to a number of cellular and molecular biology techniques including mammalian cell culture, RNA and protein isolation, gene and protein expression and ROS detection. Students are expected to participate in lab meetings and journal clubs and present their data at local and/or national meetings. 

Dr. Bruce F. Smith: Molecular Genetics Of Inherited Disease And Cancer.  Several projects are available in the area of gene therapy for muscular dystrophy and a variety of cancers.  In the area of muscular dystrophy, students will work directly with affected and carrier dogs assessing the disease and its progression.  In addition, the latest gene therapy vectors are now being tested in affected dogs, and students will have the opportunity to assist in evaluating the efficacy of these treatments from the level of the whole dog to the expression of specific genes.  Cancer projects include laboratory studies and pre-clinical and clinical trials for dogs with osteosarcoma, lymphoma, melanoma and breast cancer.  These studies involve the administration of gene therapy vectors, and the assessment of patient progress, as well as detailed laboratory assessments of the impact of the therapy.  Projects involve the use of a wide variety of techniques including RNA and DNA isolation, quantitative PCR amplification, cell culture and flow cytometry as well as animal handling, phlebotomy, bone marrow aspiration, tissue biopsy and necropsy.

Dr. Elizabeth Spangler:  Application of Thromboelastography (TEG®) to evaluate coagulation status in dogs.  TEG® is a method that evaluates coagulation in a whole blood sample, and thus includes contributions from both plasma coagulation factors and cellular elements (RBCs, platelets).  Modifications of the standard TEG® protocol have been developed to evaluate the effects of heparin on coagulation, and to isolate the contribution of platelets to clot formation (Platelet Mapping).   Future research projects will investigate the use of TEG to monitor hemostasis in dogs with various clinical abnormalities, as compared to standard coagulation tests.  In addition, in vitro studies are planned to examine the impact of therapeutic measures on TEG results.

Dr. Debra Taylor and Dr. John Schumacher:  We are investigating relationships of physical and radiographically measured foot parameters to one another and to lameness.  We  also plan to investigate the efficacy of the drug ketamine for nerve blocks of lame horses as well as the efficacy of a new approach to the proximal interphalangeal joint. 

Dr. Robyn Wilborn and Dr. Aime Johnson:   Equine Theriogenology.   The student will be conducting a research project involving mares.  The project will involve heat/estrus suppression in mares by using a subcutaneous hormone implant.  The student will be responsible for placing the implants and evaluating estrus behavior in the mares using a stallion as well as trans-rectal palpation and blood collection twice weekly.  This is a follow-up project to a previous study using similar implants.