Dr. Jean Hall

Dr. Jean Hall earned her B.S. at Oregon State University, then a D.V.M. at Washington State University. She then went to Colorado State University for an M.S and Ph.D.  Her post doctoral work was completed at Oregon Health Sciences University.  Dr. Hall is currently a professor in the College of Veterinary Medicine, Department of Biomedical Sciences, at Oregon State University.

Dr. Jean Hall’s laboratory is performing research studies to determine how nutrition affects immunity. They are interested in nutrigenomic technology, or the study of how nutraceuticals affect the expression of genes involved in the immune response. They have several dog studies in progress to determine whether dietary changes can alter innate immune responses via changes in gene expression. So far, they have shown that phagocytosis by peripheral blood neutrophils and transcript levels of genes involved in neutrophil-mediated functions are decreased in older dogs compared with dogs less than 1 year of age, which may contribute to increased morbidity and mortality with aging. Currently, they are trying to determine if dietary modifications can enhance neutrophil functions, and thus innate immunity, particularly in older dogs.

Metallic selenium

Dr. Hall’s other research projects involve sheep and cows supplemented with selenium (Se) and its effects on the immune response. Selenium has been known to function as a nutrient for over 50 years. However, the dietary requirements of selenium for optimal immune function remain to be determined. In addition, the efficacy of organic versus inorganic sources of selenium has not been thoroughly investigated. Dr. Hall’s goals are to determine if supplementing selenium at levels above those currently recommended can improve innate and adaptive immune responses, and whether organic selenium has increased bioavailability compared to inorganic selenium. Agronomic biofortification is defined as increasing the bioavailable concentration of an essential element in edible portions of crop plants through the use of fertilizers. They are also investigating the potential for using Se-containing fertilizers to increase crop Se concentrations.

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Dr. Mahfuz Sarker

Dr. Mahfuz Sarker completed his BS and MS degrees from University of Dhaka, Bangladesh, in 1982 and 1985, respectively.  He is currently a tenured associate professor with joint appointment in the Department of Biomedical Sciences, College of Veterinary Medicine and Department of Microbiology, College of Science.

Kathy Magnusson, Brenna Brim and Siba Das recently published an invited review, entitled “Selective vulnerabilities of N-methyl-D-aspartate (NMDA) receptors during brain aging” to the open access online journal Frontiers in Aging Neuroscience (Front. Ag. Neurosci. 2:11. doi: 10.3389/fnagi.2010.00011). The focus is on the N-methyl-D-aspartate (NMDA) receptors, which are present in high density within the cerebral cortex and hippocampus and play an important role in learning and memory. NMDA receptors are negatively affected by aging, but these effects are not uniform in many different ways. This review discusses the selective age-related vulnerabilities of different binding sites of the NMDA receptor complex, different subunits that comprise the complex, and the expression and functions of the receptor within different brain regions.  Spatial reference, passive avoidance, and working memory, as well as place field stability and expansion all involve NMDA receptors. Aged animals show deficiencies in these functions, as compared to young, and some studies have identified an association between age-associated changes in the expression of NMDA receptors and poor memory performance. A number of diet and drug interventions have shown potential for reversing or slowing the effects of aging on the NMDA receptor.  On the other hand, there is mounting evidence that the NMDA receptors that remain within aged individuals are not always associated with good cognitive functioning. This may be due to a compensatory response of neurons to the decline in NMDA receptor expression or a change in the subunit composition of the remaining receptors. These studies suggest that developing treatments that are aimed at preventing or reversing the effects of aging on the NMDA receptor may aid in ameliorating the memory declines that are associated with aging. However, we need to be mindful of the possibility that there may also be negative consequences in aged individuals.

Dr. Manoj Pastey

Dr. Manoj Pastey completed his veterinary degree program in India in 1988 and joined University of Maryland, College Park, for MS and PhD degree programs. In 1997, he joined Vanderbilt University Medical Center as a post doctoral fellow.  In 2001, Pastey worked as a staff scientist at Vaccine Research Center, National Institutes of Health, Bethesda, before he joined the Department of Biomedical Science, College of Veterinary Medicine, Oregon State University as an assistant professor in 2004.

Dr. Manoj Pastey’s laboratory is conducting research work on the pathogenesis of influenza, HIV, and respiratory syncytial virus (RSV).

Proteomics– Each sample that was run on a 2-D gel was labeled with a fluorescent dye. Once each gel is imaged at the different wavelengths; the overlay of those images can then be used to see where the expression is differential. The identical protein between groups can be seen in yellow where as differentially expressed proteins appear in red/green. Left: Coinfection with S. aureus and influenza. Right: S. aureus infection with uninfected control.

Influenza Research Study: Each year, influenza kills approximately 36,000 people in the United States. These deaths are mainly due to secondary bacterial infection. Therefore, we are focusing our research on identifying biomarkers in blood and urine for respiratory tract dysfunction caused by co-infection of Staphylococcus aureus and influenza virus. Accomplishments of the proposed goals will help us predict the evolution of S. aureus super-infection in patients with H1N1 influenza virus disease.  Using mice co-infected with influenza virus and S. aureus, gene expression changes obtained from DNA-microarrays and proteomic changes obtained from mass spectrometry will aid in identification of early and clinically relevant diagnostic and prognostic bio-markers.  This knowledge will allow development of a predictive statistical model to afford a better understanding of virulence mechanisms and pathogenesis of respiratory tract co-infections by these microorganisms, such that risk of pneumonia can be assessed and effective preventative or treatment regimens can be initiated in infected individuals.

HIV Research Study: Our laboratory is testing a polyherbal vaginal microbicide named “BASANT” that has been shown to inhibit a wide range of sexually transmitted pathogens including HIV. Preliminary studies have also shown safety and acceptability in Phase I (acceptability and toxicity study) human trials in India.  Therefore, the next step is to verify the effectiveness of the BASANT in preventing HIV transmission in vivo. The central goal of these studies is to understand the mechanism of microbicide anti-HIV action and to determine the efficacy of BASANT in preventing intravaginal/intrarectal HIV transmission in humanized mouse model. In addition, the efficacy of BASANT will be evaluated against six major globally prevalent strains of genetically and biologically characterized HIV-1 isolates.

Colocalization of RSV M and AP3M1, post 24 hours. Upper left: DAPI. Upper center: Ap3m1. Upper right: RSV Matrix. Bottom left: Merge.

RSV Research Study: Respiratory Syncytial Virus (RSV) is a leading cause of bronchopneumonia in infants and the elderly. There are no vaccines or effective treatment available. Knowledge of viral and host protein interactions is important for better understanding of the viral pathogenesis and may lead to development of novel therapeutic drugs. In our lab, we have shown that Respiratory Syncytial Virus Matrix (M) protein interacts with cellular adaptor protein complex (AP)-3 and its medium (µ) subunit. A yeast two-hybrid assay indicated a novel protein-protein interaction that was then further confirmed in a mammalian system by co-localization between the RSV M and AP3 µ 1 proteins in a cytoplasmic defined region via Confocal Laser Scanning Microscopy (CLSM) analysis. Further evidence of this novel interaction was indicated via the presence of a known adaptor protein µ subunit sorting signal sequence, YXXL that is conserved across various animal RSV M proteins. Subsequent Western blot studies also showed a specific upregulation in the amount of AP3 µ 1 protein found in the cell during RSV infection, while corresponding subunits of the AP3 complex were unaffected. The interaction of AP3 µ 1 with RSV M represents a critical insight into the life cycle of this important virus and may represent a novel drug target.

Dr. Patrick Chappell

Dr. Patrick Chappell is currently an assistant professor in the Department of Biomedical Sciences at the College of Veterinary Medicine. From 2006 until 2009, he was a research assistant professor in the Department of Zoology at OSU. He received his bachelor’s degree in psychology from Emory University in Atlanta, Ga. and his Ph.D. in neuroscience from the Northwestern University Institute for Neuroscience in Chicago, Ill. He completed his dissertation work on the role of hypothalamic progesterone receptors in the generation of preovulatory surges in female rodents. Dr. Chappell performed his postdoctoral work in the Department of Reproductive Medicine at the University of California in San Diego, California where he received a National Research Service Award and Mentored Career Fellowship from the National Institutes of Health.

GnRH (green) co-localized with the circadian clock protein BMAL1 (red) in a coronal slice of mouse hypothalamus.

Dr. Chappell’s laboratory predominantly investigates the role of endogenous intracellular circadian clocks in the neuroendocrine regulation of reproduction in mammals. Using a combination of molecular biological and physiological techniques, they are exploring how oscillatory gene expression patterns in hypothalamic gonadotropin-releasing hormone (GnRH) neurons modulate secretion of this neuropeptide, which is crucial for gamete production, steroid hormone production, and ovulation in females. GnRH stimulates the anterior pituitary to secrete the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are required for gametogenesis and steroidogenesis in the testes and ovaries. GnRH release patterns vary from episodic pulses that occur every 30-60 minutes to dramatic surges that initiate ovulation in females. Interestingly, ovarian estrogen acts as both a negative feedback inhibitor of GnRH release during the early follicular and luteal phases and a positive feedback stimulation of GnRH release just prior to ovulation. They are exploring how this steroid hormone may perform this dual role by interacting with endogenous transcriptional oscillators within GnRH neurons and within other hypothalamic neuronal populations. The lab utilizes several models of molecular circadian clock disruption, and is determining the necessity of cell-specific clocks using multiple transgenic mouse lines. Additionally, they have created several sub-cloned immortalized cultured GnRH-secreting neuronal cell lines in which they can monitor clock oscillations concomitantly with peptide secretion, and in which they can reversibly disrupt clock function. Specific projects available include examining the effects of estrogen feedback on GnRH neuronal gene expression patterns, activity, and secretion, using both in vitro cell culture and in vivo mouse models. These studies will provide insight into broad mechanisms of endocrine neurosecretion, and advance circadian biology by exploring how transcriptional oscillations can control synchronous multi-cellular events to regulate numerous biological processes and even orchestrate complex behaviors. Potential applications of this research include new directions in treating a range of reproductive physiological disorders that result from malfunction of hypothalamic neurosecretion, including polycystic ovarian syndrome (PCOS) and primary ideopathic hypogonadism, both of which are associated with atypical hormone release patterns.

The Chappell lab has also opened a new line of investigation into the role of clock gene expression patterns in the initiation and progression of hormone-responsive reproductive cancers, such as prostate and breast cancer. A recent publication from their group demonstrated that healthy murine prostate epithelial cells exhibit robust oscillations of circadian clock genes, and they have recently determined that cancerous cells lack these rhythms. The lab is exploring the possibility that clock dysregulation may represent one etiology of cancer in these cells, particularly in the transition to a hormone-refractory state, and is investigating physical interactions between circadian clock components, the androgen receptor, and modulators of chromatin remodeling. This research could provide insight into novel chronotherapeutic treatments of reproductive cancers, by determining how endogenous clocks interact with cell cycle regulators and steroid hormone receptors, and how these inherent timing mechanisms may be involved in determining whether prostate epithelial cells progress toward either apoptosis or proliferation. His lab utilizes methodologies ranging from real-time quantitative RT-PCR, transient transfection of cultured cells, evaluation of xenografted tumors in mice, and monitoring gene expression and protein abundance changes in cells using fluorescence microscopy and luminometry.

GnRH secretion profile of perifused GT1-7 cells.

Immortalized GnRH-secreting GT1-7 cells.

Dr. Michael Kent

Dr. Michael Kent-Microbiology

Dr. Michael Kent completed his BS degree in Fisheries at Humboldt State University in 1997, earned his MS degree in Biology at San Diego State University in 1981, then completed a PhD in Comparative Medicine at the University of California at Davis in 1985. From there he went to Battelle Marine Research Laboratory in Sequim, Washington to do a post-doctoral fellowship from 1986-1988.  He spend the following 11 years working as Research Scientist, Fisheries and Oceans Canada, at the Pacific Biological Station in Nanaimo, British Columbia. Dr. Kent was head of the Fish Health, Parasitology, and Genetics Section there from 1997-1999.  He joined Oregon State University in 1999, and is currently a professor with joint appointments in the Dept. of Biomedical Sciences in the College of Veterinary Medicine and Dept. of Microbiology in the College of Science.

Two zebrafish with Pseudoloma infections. Fish are emaciated and lower fish has skeletal deformaties.

Dr. Kent’s main areas of research are diseases of fishes and parasitology in general. Since joining OSU in 1999, his group has been investigating diseases of zebrafish, through support by NIH National Center of Research Resources.  There has been a dramatic increase in the number of laboratories using zebrafish as a model organism in biomedical research.  Kent’s lab is conducting research leading to development of methods to control or eliminate the two most common infectious diseases affecting zebrafish facilities; microsporidiosis (caused by Pseudoloma neurophilia) and mycobacteriosis.  Dr. Luiz Bermudez is a key collaborator with the latter. In collaboration with Dr. Robert Tanguay here at OSU and support of the NIEHS Environmental Health Sciences, we have developed the first Specific Pathogen Free (SPF) zebrafish laboratory, for Pseudoloma neurophilia, at the OSU Sinnhuber Aquatic Research Laboratory.

OSU was recently awarded a T32 Training Grant from NIH NCRR for training. Dr. Tanguay is the Director and Dr. Kent is the Deputy Director.  The grant provides training for veterinarians in the use of aquatic species in biomedical research.  Dr. Trace Peterson, DVM, is our first candidate.  He works in Dr. Kent’s laboratory studying modes of transmission of mycobacteria.

Metacercariae of Apophallus sp. in the muscle of coho salmon. Heavily infected fish may have 4,000 metacercariae/gram of muscle

Dr. Kent’s lab also studies the impacts of chronic parasite infections on survival of wild coho salmon in Oregon.  This project is funded by Oregon Dept. Fish & Wildlife (ODF&W) through the ODF&W Microbiology Fellowship to a PhD graduate student in Kent’s lab, Jayde Ferguson.  We have recently documented exceptionally heavy infections in certain populations of coho salmon.  Jayde is focusing his research on impacts of these parasites, particularly metacercariae of digenetic trematodes, on overwinter survival in coho salmon from the West Fork Smith River.  Two other projects, in collaboration with Dr. Carl Schreck, Department of Fisheries and Wildlife, are investigation of pathogens associated with prespawning mortality in Chinook salmon in the Willamette River, and distribution of intersex trout in National Parks.

Dr. Kent also studies terrestrial parasites.  Recent projects include the study of distribution and taxonomy of spirurid nematodes (Cylicospirura spp.) associated with  large nodules in the stomach of cougars and bobcats, also lead by Jayde Ferguson in the Kent lab and collaborators from ODF&W. They are also evaluating and implementing a new diagnostic test for Haemonochus contuntorus, a nematode parasite that causes serious disease in sheep, goats and llamas in Oregon.  This infection is diagnosed by finding parasite eggs in fecal samples, but it is very difficult to separate the eggs of Haemonchus from other less pathogenic nematodes based on sizeand shape of the egg.  We are modifying and evaluating a lectin-based test developed in Australia, and our modified test is now available to farmers and their veterinarians through the Veterinary Diagnostic Laboratory.   This work was conducted in collaboration with a veterinary student, Megan Jurasek, Dr. Kent, and Janell Bishop-Stewart from the VDL.

Haemonchus eggs and larva, all staining green with special fluorescent stain and observed under UV light.Courtesy of Bob Storey, University of Georgia.

Cylicospirura subequalis associated with large stomach nodule in a cougar. Courtesy of Dr. Colin Gillin, Oregon Department of Fish and Wildlife.