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Current Research

Research Project Descriptions – 2014

Dr. Benson Akingbemi:  Effects of Environmental Chemicals in the Male Reproductive Tract. Reproductive anomalies such as impaired semen quality, cryptorchidism, and hypospadias have increased with the growing use of industrial chemicals in the last 40 years.  Therefore, there is growing public concern that chemicals in the environment (food, air, water) may have adverse effects on reproductive health.  The chemicals alter the endocrine profile by acting through steroid hormone receptors, which are expressed at high levels in the reproductive tract.  Ongoing studies in our laboratory are focused on two endocrine disrupting chemicals (EDCs) that are abundant in our environment (bisphenol A and phthalates), will assess the anti-müllerian hormone peptide as a target for EDCs, and identify mechanisms of EDC effects at all levels of the hypothalamus-pituitary-gonadal axis.

Dr. Frank Bartol:  Research in the Bartol lab focusses on identification of factors affecting uterine development and function with emphasis given to domestic ungulate species and companion animals, now including the horse.  Analytical procedures employed include advanced histotechniques such as multispectral imaging and laser microdissection.  Recent publications and reviews of this work can be found via Pubmed using the following PMID numbers: 23619340, 23136302, 23100582, 22033320, 22133692, 22959316


Dr. Dawn Boothe: Mechanisms of Antimicrobial Resistance. The laboratory has investigated molecular mechanisms of resistance, particularly in E. coli  in response to antimicrobial and particularly fluoroquinolone therapy. This summer (2014), the laboratory would like to begin to investigate the relationship between non-antimicrobial drugs used therapeutically (eg, anticancer drugs, antisecretory drugs) and their impact on patterns of gastrointestinal microbiota populations (primarily based on molecular characterization of fecal microflora) and emerging resistance resulting from activation of efflux pumps.


Dr. Mary K. Boudreaux and Dr. Pete W. Christopherson:   Inherited Diseases of Hemostasis. Our laboratory is involved with evaluating inherited platelet and coagulation disorders in dogs, horses, and cows at the functional, biochemical, and molecular level. Students working in our 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. Sue Duran:  Formulations and Preparations of Transdermal Pharmaceuticals to Treat Infectious Diseases.  Various enhancers will be developed to treat infectious diseases from topical formulations.  The students will learn to formulate products, then test them in-vitro and in-vivo for efficacy.  Good manufacturing practices (GMP) will be taught to include product development, formulations and quality control to meet FDA standards.  This is a good introduction for a student who has interest in becoming an industrial pharmaceutical veterinarian.


Dr. Chad Foradori:   Effects of Environmental Contaminants on Neuroendocrine Function. The laboratory focuses on the neuroendocrine control of reproduction. Specifically, what factors mediate the release of gonadotropin releasing hormone (GnRH) and the subsequent release of gonadotropins (luteinizing hormone and follicle stimulating hormone) from the anterior pituitary. GnRH regulation requires the translation of neural and hormonal inputs into a precisely regulated output to achieve normal sexual development and gonadal function. Changes in the pulsatile secretion of GnRH are critical for the regulation of events leading to ovulation, inhibition of ovulation prior to puberty and during other physiological periods of infertility. Despite the importance of GnRH neuronal activity in mammalian reproduction, little is known about the inputs controlling the coordination of GnRH neurons resulting in pulsatile and preovulatory release. The paucity of knowledge is due to the fact that GnRH neurons have a limited number of synaptic inputs and express a relatively small number of steroid receptors. One way to identify the underlying mechanisms involved in the normal control of GnRH neurons is to examine the system during periods of distress or after developmental insults. Therefore, my research examines the effects of environmental factors, which may alter GnRH activation. In doing so, we will be better able to identify those factors essential for normal reproductive function and develop intervention strategies to protect against environmental factors that may perturb normal reproductive function


Dr. Reid Hanson: 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.  Cartilage surface geometries will be characterized using nano-scale surface profilometry, 3 and 7 Tesla magnetic resonance imaging (3T, 7T-MRI) and mathematical and numerical modeling techniques to analyze the structure of the surfaces over many scales. The new 7T-MRI provides a unique opportunity to characterize cartilage at the smallest scales ever achieved while in situ (although still much larger than what is possible with current surface profilometers). The key is to mesh the geometries at the two different scales into one complete model.


Dr. Michael H. Irwin:  Rodent models of mitochondrial disease.  Ongoing studies revolve around innovative approaches toward manipulation of mitochondrial genetics, modeling of mitochondrial complex I dysfunction, and testing of potential therapies in mice and rats. We are developing animal models of severely debilitating (and often lethal) human disorders caused by genetic mutations that affect mitochondrial function. Our 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 and cultured cell line characterizations, 2) developing molecular/cloning skills and 3) participating in the creation of genetically engineered laboratory animal models.


Dr. Jacob Johnson: Avian Anesthesia and Pain Management. The drugs available to provide balanced anesthesia to birds are limited and most anesthesia has been provided through the exclusive use of inhalants, such as Isoflurane. While this approach has been overall effective, it is not ideal as the high concentrations needed to produce complete immobility in the face of surgical stimulation suppress the ventilatory and cardiovascular system. I am continuing to investigate two new drugs in avian anesthesia: dexmedetomidine and rocuronium. Opioid analgesics have variable success in providing intraoperative analgesia to avian species, so the hypothesis being investigated is that dexmedetomidine would provide more reliable analgesia without significant cardiovascular effects. Rocuronium is a paralytic that could allow for muscle relaxation, therefore reducing inhalant requirements. Because a bird’s iris is partially controlled by skeletal muscle it may also allow for ocular surgeries that require pupil dilation, such as cataract surgery.


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 10 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 2014 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:  Antitumor Effect of the Plant-based Omega-3 Stearidonic Acid SDA) and Docetaxel (DOC) in Human Prostate Cancer Cell Lines. Docetaxel (taxane) is a first choice cytostatic drug in treatment of many cancers but, among its several side effects, is depressed immunity. Stearidonic omega-3 fatty acid (SDA) has immunity protective characteristics and, therefore, we  will investigate the combinatory effects of DOC and SDA on proliferation/viability in the human prostate cancer (PCa) cell lines LNCaP, PC3, and DU145 as well as possible modulatory effects on expression of androgen receptor (AR), PPAR, and NF-κB PCa-related nuclear transcription factors. Equipotent combinations of DOC and SDA based on 2-fold dilutions and constant combination ratios will be derived from the calculation of IC50 values. Combination index (CI) will be determined using the Chou-Talalay method based on the median-effect equation and the mass action law. We will use immunocytochemistry, real-time PCR, and transfection assays to demonstrate inhibition of agonist-activated AR and PPARγ.


Dr. Douglas Martin:  Molecular Therapy of Neurodegenerative Disease. The laboratory’s model of neurodegenerative disease is feline gangliosidosis, similar to human Tay-Sachs disease, a disorder in which abnormal function of lysosomes causes progressive nervous system dysfunction and death. Though first reported in 1881, Tay-Sachs disease remains virtually untreatable, and affected children die by 5 years of age after spending several years in a semi-vegetative state. 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 including intracranial injection of therapeutic agents, MRI-based analyses of disease progression, and biochemical and molecular biological evaluation of therapeutic benefit. 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:  Risk Factors and Complications of Laparoscopy in Horses.  Laparoscopic procedures have become commonplace in the field of equine surgery.  However, the risks of the technique have not been fully investigated.   Our goal is to further categorize the link between abdominal insufflation and organ ischemia in the horse and its effects on prognosis and outcome of laparoscopic surgery.  Students working with us will have the opportunity to assist us in gathering data to monitor the effects of intra-abdominal hypertension during experimental laparoscopy.  A specific portion of the research will involve the measurement of intra-abdominal pressures in the abdominal cavity of the horse to further define normal values during and after surgery.  An additional portion of this project will involve participation in ongoing research investigating epiploic foramen entrapment, a specific type of small intestinal strangulating colic. 


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 may work directly with affected and carrier dogs assessing the disease and its progression.  In addition, the latest genetic approaches may be used to understand the basis of components of the disease.  Cancer projects include laboratory studies and pre-clinical and clinical trials for dogs with osteosarcoma, lymphoma, melanoma, mast cell tumor and breast cancer.  These studies involve the administration of gene therapy vectors and novel biological molecules, 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, tissue biopsy and necropsy.


Dr. Elizabeth Spangler:  Application of whole blood assay methods for evaluation of blood coagulation and platelet function.  A new instrument for evaluation of platelet function in samples of whole blood (Multiplate) was recently installed in the clinical pathology lab.   We will begin to investigate the use of this instrument by evaluating blood samples from healthy animals.   In order to model situations that are commonly seen in sick animals, we will also evaluate the effects of anemia and/or administration of IV fluids through in vitro manipulation of blood samples from healthy dogs.  Finally, we will recruit blood samples from a population of sick animals in order to investigate how platelet function is affected by different types of illness.


Dr. Allision Stewart:  Pigeon fever is a re-emerging disease affecting horses caused by Corynebacterium pseudotuberculosis biovar equi that is currently spreading to non-endemic regions.  Measurement of antibody titers (serology) is a diagnostic test used for diagnosis of this disease, but little information is available concerning the interpretation of this test in non-endemic areas, such as Alabama. Further investigation about the diagnosis of pigeon fever is needed to control disease extension to horses in non-endemic regions. A survey has been designed to measure the antibody titers present in 487 apparently healthy horses in different counties of Alabama. The student would be involved in the epidemiological study- collating data, processing samples and contacting owners and referring veterinarians by phone. A basic horse background and an interest in data management (excel) and epidemiology would be desirable.

The student would be working closely with Drs Marta Barba, Allison Stewart and also Drs Anne Wooldridge and Thomas Passler. Additional large animal research experiences would be provided with these doctors.


Dr. Frederick van Ginkel:  Our research is focused on measuring and inducing mucosal and systemic immunity to infectious bronchitis virus, an avian pathogen that causes considerable economic losses in the poultry industry despite vaccination. We are generating novel vaccine vectors to induce strong cross-protective immunity to different IBV serotypes. We will analyze the ability of IBV vaccines and IBV vaccine vectors to generate protective immune responses in the mucosal and systemic immune compartments employing techniques such as quantitative RT-PCR, ELISA, ELISPOT assays and peptide arrays. 


Drs. Robyn Wilborn & Aime Johnson:  Opportunity available to assist with two pharmacokinetic studies in foals.  The primary project involves administration of altrenogest (Regumate) orally to mares during peak lactation and measurement of the concentration of drug available in the milk as well as the systemic circulation of the nursing foal.  Because this medication is a powerful hormone, it is potentially capable of altering reproductive development in the nursing foal and this has never been studied before.  The student will also have the opportunity to participate in another ongoing pharmacokinetic study involving the administration of Keppra (an anti-seizure drug) to foals.  Although previous experience with horses is not required, some level of basic horse experience is certainly helpful.  *Due to safety concerns regarding the medications being studied, this project is not recommended for students who are pregnant or might become pregnant during the course of the study.*  AN INTEREST MTG WILL BE HELD ON TUES, JAN 21 at NOON IN THE CAFETERIA.


Dr. Anne Wooldridge:  My lab is interested in vascular disease and metabolic disease in the horse.  We are currently collaborating closely with Dr. Elizabeth Lipke in the Department of Chemical Engineering to culture endothelial progenitor cells from horses and combine those cells with different biomaterials to study vascularization. This process is essential for tissue engineering and regenerative therapy.  Projects for the summer may involve primary cell culture from blood or bone marrow of horses, characterization assays, flow cytometry, immunofluorescence, and analysis of cell behavior within 3-dimensional biomaterials. 

 

 

 

 

 

 

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