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  Home > Current DVM Students > Summer Scholars Program > 2014 Summer Scholars Faculty Research Projects
 

2014 Summer Scholars Faculty Research Projects

Project categories:


 Comparative Medicine

 

Project Title: Stem cell differentiation in novel biomimetic hydrogels
Mentor: Dr. Timothy D. O'Brien
Contact: obrie004@umn.edu

Project Description: My laboratory is developing novel biomimetic hydrogels which can be used for development of artificial tissues for in vitro disease modeling, for regenerative medicine applications, as platforms for cell and tissue transplantation and many other applications. The field of 3-D cell culture is rapidly expanding as it is found that cells exhibit novel metabolic, functional, developmental, and organizational features in 3-D which were not evident in conventional 2-D cell culture. We are developing protocols and hydrogel formulations to differentiate mesenchymal stem/stromal cells to bone, cartilage, and adipose tissues. We have also recently observed spontaneous differentiation of induced pluripotent stem cells (iPSC) to neural organoids in one of the hydrogel formulations and are exploring other applications for these matrices for iPSC culture and differentiation. Projects for a summer scholar would involve aspects of these lines of investigation.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Population MedPo

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Project Title: Neural components of myocardial infarction induced heart failure
Mentor:  Dr. John Collister
Contact: colli066@umn.edu

Project Description: Coronary artery disease leading to myocardial ischemia and infarction (MI) is the primary cause of chronic heart failure (HF). Despite advances in the diagnosis and treatment of heart disease, MI induced HF continues to be a leading cause of morbidity and mortality in the United States. In this application we will use the rat model of coronary artery ligation to create a myocardial infarct and eventual heart failure. It is well known that the renin angiotensin (RAS) is activated and produces much of the pathophysiology of HF. It is also well known that increased RAS in the central nervous system contributes to HF, although the exact locations are not known. Additionally, it has been shown that excessive reactive oxygen species (ROS) in the brain contribute to the pathophysiology of post MI HF in the rat in part due to increased central nervous system RAS activity. In this application we will specifically examine the role of ROS in the median preoptic nucleus (MnPO), a site known to be sensitive to both increased RAS and ROS, in the progression and pathophysiology of MI induced HF in the rat. It is likely that ROS, such as O2•-, in the MnPO are important mediators in the central mechanisms mediating the pathophysiology of HF and therefore we will examine the role of MnPO O2•- in the pathophysiology of HF to address the following Hypothesis: Elevated O2•- in the MnPO contributes to the pathophysiology of HF and decreased cardiac function.

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterinary Biosciences

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Project Title: Use of CD200 competative inhibitors to suppress MDSC formation
Mentor: Dr. Michael Olin
Contact: olin0012@umn.edu

Project Description: We have been focusing our work on the understanding of tumor-induced immunosuppression. Recently, we discovered a soluble form CD200 enhanced in tumor bearing animals. CD200 is an immunosuppressive protein expressed on a variety of cell types negatively regulating immune functions. CD200 is highly expressed in a variety of human tumors including melanoma and glioblastomas. Moreover, CD200 is co-expressed on tumor stem cells, hypothesized to be a means to escape immune surveillance. In humans, soluble CD200 levels in the plasma isolated from patients with chronic lymphocytic leukemia correlated with tumor burden and disease state. We demonstrated increased levels of CD200 in serum of our glioblastoma and ependymoma immunotherapy patients when they progressed and went off trial. CD200 is an immunosuppressive protein expressed on a variety of cell types capable of regulating the immune system in many tissues. CD200 acts through its receptor (CD200R) on multiple leukocytes including monocytes, granulocytes, dendritic cells, T cells and B cells. These interactions include the induction of IL-10 and two other highly immune-suppressive isoforms of TGFβ, IDO (indoleamine2, 3-dioxygenase), differentiation of CD4+CD25+FoxP3+ T regs and myeloid derived suppression cells (MDSC) populations which are involved in the down regulation of myeloid and lymphoid cells negatively influencing the immune system following antigen challenge. Recently, we developed a method to reverse the immune suppressive effects of CD200 in both glioma and breast carcinoma models. However the question of weather the inhibitors revised the suppressive environment and not just enhanced immunogenicity arose. In this proposed project, we will use our novel competitive inhibitors in glioma bearing mice and compare the development of MDSC and T regulatory cell populations over time. Murine glioma GL261 will be inoculated into mice. Mice will be vaccinated with tumor lysate +/- CD200 competitive inhibitors. Mice will be bled weekly; whole blood will be analyzed for MDSC and T regulatory cell percentages. In addition, CD200 will be measured from serum. Mice from each treatment group will be sacrificed weekly and analyzed by immunochemistry for tumor infiltrating lymphocyte populations. Mice will be imaged for tumor growth and monitored for survival. 

Eligible Funding Sources: Merial, CVM, Skadron Fellowship

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Project Title: Role of CD44 signaling in canine hemangiosarcoma
Mentor:  Dr. Jamie Modiano
Contact: modiano@umn.edu

Project Description: CD44 is a cell-surface glycoprotein and the receptor for hyaluronic acid (HA). In cancer, this molecule has been shown to participate in a variety of biological functions such as cell proliferation, migration, metastatic process, and the activity of cancer stem cells. Canine hemangiosarcoma (HSA) is a common and lethal cancer. HSA is prevalent in certain breeds such as Golden Retrievers, German Shepherd Dogs, and Portuguese Water Dogs, although the risk of the disease is not limited to a single breed. Dogs with the disease have poor prognosis and there are no effective therapies. We believe that to treat this disease effectively, we must first understand its fundamental biology. In a previous study, we showed that CD44 expression is significantly higher in HSA cells than in normal endothelial cells. We have validated this elevation of CD44 gene and protein expression in cultured-canine HSA cell lines; however, the functional role of CD44 on the pathogenesis of HSA remains to be determined. As part of this project, the summer scholar will establish the foundation to determine the function of CD44 in canine HSA. We propose that CD44 signals contribute to the pathogenesis of HSA by interacting with stromal HA. The hypothesis for the project is that interactions between HA and CD44 enhance proliferation, migration, and self-renewal of HSA cells in culture. CD44 gene and protein expression will be evaluated in four independent canine HSA cell lines by qRT-PCR and flow cytometry, respectively. CD44 signaling in HSA cells will be evaluated by measuring calcium mobilization using flow cytometry and phosphorylation of Src tyrosine kinase family members using Western blotting. Proliferation, migration, matrix invasion, and self-renewal will be measured using conventional procedures such as the MTS assay, scratch assays, Boyden chamber (transwell) assays, and non-adherent sphere formation in cultured HSA cells treated with and without HA. This project will provide the summer scholar basic laboratory skills, as well as an opportunity to expand their knowledge in HSA, comparative cancer biology and veterinary oncology.

Eligible Funding Sources: Merial, NIH, CVM, Skadron Family Fellowship, Department of Veterinary Clinical Sciences

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Project Title: What is the role of warm-sensing receptors (TRPV1) in muscle and tactile pain?
Mentor:  Dr. Alice Larson
Contact: larso011@umn.edu

Project Description: TRPV1 receptors are sensitive to heat and to capsaicin. Heat is analgesic in some types of pain, but it promotes hyperalgesia (enhanced pain sensitivity) in most models of pain studied. For example, heat is analgesic in conditions of muscle pain (e.g. overuse of muscles, fibromyalgia) but enhances the pain of burn injuries. We hypothesize that muscle pain is not normally mediated by TRPV1 sites but is inhibited by them. To test this, we will measure two types of muscle pain (grip force and von Frey fiber sensitivity) in response to desensitization or activation of TRPV1 receptors. We will also examine the effect of TRPV1 antagonists, and of warm and cold environments on muscle pain. Because TRPV1 sites are upregulated by inflammation, we will also determine whether lipopolysaccharides (LPS) influence muscle pain differently than in saline-injected controls and whether the effect of LPS is mediated by increased TRPV1 activity. Based on our preliminary data, we predict that grip force responses are inhibited by warmth and by increases in TRPV1 activity while tactile sensitivity is increased by warmth and by TRPV1 activity.

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterinary Biosciences

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Project Title: What is the role of capsaicin-sensitizing (TRPV1) receptors in depression?
Mentor:  Dr. Alice Larson
Contact: larso011@umn.edu

Project Description: We have recently reported that capsaicin-sensitive (TRPV1) receptors promote depressive-like behavior (immobility) in the forced swim test. As a result, blockade of TRPV1 activity using a desensitizing dose of RTX is antidepressant while a low, non desensitizing dose that activates those sites is depressive. This suggests that the forced swim elicits the release of endogenous TRPV1 ligands. The question arises whether the persistent activation of TRPV1 receptors plays a role in the mediation of depressive behavior in models of endogenous depression, such as, amphetamine withdrawal, reserpine treatment, olfactory bulbectomy or chronic heterotypic stress. We hypothesize that TRPV1 sites normally inhibit mood and that inflammation or chronic stress enhances their contribution to depression by upregulating their receptor population. We can test this by examining the effect of high desensitizing doses of RTX compared to lower doses and the effect of TRPV1 receptor antagonists on responses in the forced swim test after the development of depression in the models listed above. We predict that decreased TRPV1 receptors blocks depression whereas upregulation of these sites in response to inflammation increases depressive behavior measured using the forced swim.

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterina

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Project Title: Impact of porcine T cells response on the evolution of Swine Influenza virus (SIV)
Mentor: Dr. Maxim Cheeran
Contact: cheeran@umn.edu

Project Description: Influenza viruses are well known for their ability to generate antigenic variations that consequently enable immune evasion. This viral characteristic is the bane of vaccine efforts against influenza, including in domestic swine production. Antibody response is the predominant correlate for protection during influenza infections and has been extensively studied for its effect on generating strain variations. While it is clear that the CMI responses play a significant role in cross protection against influenza virus subtypes, there is a significant gap in knowledge regarding its influence on antigenic variation. Our laboratory studies cell-mediated immune responses to SIV with the goal: (1) To identify the major SIV determinants of porcine immune response (2) To determine how these determinants change on the virus under selective immune pressure Initial efforts in the lab are focused on understanding the SIV epitopes recognized by porcine T lymphocytes in response to infection and/or vaccination. These studies are expected to provide tools required to assess T cell responses against emerging influenza viruses in the domestic swine population that would help in predicting protection and developing novel vaccine strategies.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Population Medicine

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Project Title: Using genetic tools to understand the pathophysiology of dystrophic cardiomyopathy.
Mentor: Dr. DeWayne Townsend
Contact: town0045@umn.edu

Project Description: This project will is designed to answer some fundamental questions regarding the pathophysiology of dystrophic cardiomyopathy. This form of heart disease is present in patients with muscular dystrophy, the most common form of which results from the loss of the protein dystrophin. Dystrophin is thought to function as a molecular shock absorber, protecting the membrane from the forces of contraction in striated muscles. It is proposed that dystrophin may also function as a signaling scaffold, working to localize various signaling molecules to the membrane. Some of these are thought to control regional blood flow, which may result in periods of transient ischemia. Using a Cre-reporter dystrophic mouse strain, this project will use genetic elements that express Cre under hypoxic conditions. The cells of Cre-reporter mice permanently express a reporter gene following the expression of Cre. This study will directly test the presence of hypoxia within the context of an animal model of muscular dystrophy.

Eligible Funding Sources: Merial, NIH, CVM

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Project Title: High Field MRI Studies of Osteochondrosis
Mentor: Dr. Cathy Carlson
Contact: carls099@umn.edu

Project Description: Osteochondrosis is a developmental disease that is an important cause of lameness and osteoarthritis in animals. The proposed studies are designed to investigate 1) the role of epiphyseal (growth) cartilage blood supply in naturally occurring and surgically induced lesions of osteochondrosis and 2) new methods to identify cartilage necrosis occurring secondary to ischemia. We hypothesize that a defect in cartilage canal blood supply will be identified early in the disease process using high field (3T or greater) MRI techniques and that ischemic lesions will be identified prior to the time at which they are visible radiographically. The MRI studies will be done at the Center for Magnetic Resonance Imaging (CMRR); however, substantial work also will be done at the CVM (histology, image rendering, possible live animal work).

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterinary Population Medicine

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Project Title: Fate of Neural Stem cells during viral encephalitis
Mentor: Dr. Maxim Cheeran
Contact: cheeran@umn.edu

Project Description: Herpes simplex virus (HSV)-1 brain infection is the most common cause for sporadic encephalitis in the United States, which is fatal when untreated. Unfortunately, despite effective acyclovir therapy, majority of surviving patients will suffer long-term neurological impairment. Our laboratory studies a population of cells in the brain called neural stem cells (NSCs), which possess the ability to repair damaged brain tissue. NSCs utilize inflammatory cues to direct the reparative processes in the brain. However, to date nothing is known about viral-induced cues that activate NSCs. The summer research projects available in our lab for students interested in research on neuroimmune responses to HSV-1 brain infection. The projects are (1) to investigate if NSCs migrate to sites of HSV-1 induced brain damage in response to inflammatory cues generated by T cells and (2) to study the immunosuppressive effects of NSCs on CD8 T cell response during herpes encephalitis. We will utilize a well characterized mouse model of HSV-1 encephalitis to test the hypothesis that modulating neuroinflammatory responses to HSV-1 infection will foster NSC reparative properties. These are interdisciplinary studies, providing exposure to three major scientific disciplines, including virology, immunology, and neuroscience. The ultimate goal of this research is to develop a new understanding of interactions between NSCs and the immune milieu generated during viral encephalitis that will lead to new therapies for brain damage ensuing virus infection.

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterinary Population Medicine

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Project Title: Immunohistochemical characterization of canine diffuse large B cell lymphoma
Mentor: Dr. Davis Seelig
Contact: dseelig@umn.edu

Project Description: There are over 50 differing subtypes of lymphoma and leukemia in people, the vast majority of which have unique causes, risk factors, response to treatment, and prognosis. Recent work in veterinary medicine has confirmed the comparative utility of the same classification scheme (i.e. the revised World Health Organization system) in the diagnosis and classification of canine lymphoma. In part, these classification schemes stratify neoplastic populations, in part, by a combination of histologic appearance and the immunohistochemical expression of specific cell surface proteins. Through this work, the following histologic types of mature canine B cell lymphoma have been recognized: 1) diffuse large B cell (DLBCL), 2) marginal zone (MZL), 3) follicular (FL) and 4) mantle cell (MCL) lymphomas. Of these differing subtypes, diffuse large B cell lymphoma (DLBCL) is the most common subtype of lymphoma in both humans and dogs. Moreover, in people, DLBCL is a heterogeneous entity with two main subtypes – germinal center and activated, with germinal center DLBCL having a better prognosis. Some evidence suggests that most canine DLBCL may be of activated type but this suggestion requires more study with a larger group of dogs. The specific aim of this research is to use immunohistochemistry (IHC) to identify a constellation of antigens whose expression can be used to provide additional classification and prognostic information in canine DLBCL. In conjunction with collaborators at the Colorado State University Clinical Immunology Laboratory, we will evaluate the applicability and utility of a panel of antibodies in 90 cases of canine DLBCL. The antibodies we have chosen are based upon: 1) their reported utility in the dog and, for comparative purposes, 2) their usefulness in the classification of human B cell disorders (TdT, BCL6, CD10, IRF4, and cyclin D1). Based upon these results, subtype-specific profiles will be designed. This proposed research is a part of a larger American Kennel Club foundation study that seeks to create consistency in investigations of canine lymphoma and leukemia, leading to greater scientific yield in future studies. The overarching goal of our research is to create an objective classification of canine B cell lymphoma that can be applied using widely available technology which will: 1) facilitate research into both human and canine lymphoproliferative disease, 2) identify canine lymphoma therapies already well-established in human patients, and 3) position dogs to be more effective pre-clinical models for human lymphoma.

Eligible Funding Sources: Merial, CVM, Skadron Family Fellowship, Department of Veterinary Clinical Sciences

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Project Title: Histological evaluations of osteoarthritis and bone fracture repair
Mentor: Dr. Cathy Carlson
Contact: carls099@umn.edu

Project Description: Our laboratory has multiple ongoing projects focused on the histological assessment of 1) long bone fracture repair in a critical sized defect model in goats and 2) severity of osteoarthritis in aging models in mice. The fracture repair studies are designed to model and develop treatments for military combat injuries. The osteoarthritis studies are designed to determine the mechanisms and develop treatments for osteoarthritis. Although there may be some opportunities to assist with the goat surgeries, the bulk of the work in both projects includes grading and taking histomorphometry measurements of changes/lesions in histological sections. The fracture repair studies are done in collaboration with Dr. Liz Pluhar (U of MN, CVM) and Dr. George Muschler (Cleveland Clinic). The osteoarthritis studies are done in collaboration with Dr. Richard Loeser (UNC, Chapel Hill).

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterinary Population Medicine

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Project Title: EGF ligands as markers of pre-invasive breast cancer
Mentor: Dr. Kaylee Schwertfeger
Contact: schwe21@umn.edu

Project Description: Although imaging techniques have improved our ability to detect pre-malignant breast lesions, we do not yet have the ability to determine which of these lesions will progress to invasive cancers and which will remain benign. All patients diagnosed with ductal carcinoma in situ (DCIS), which is a pre-invasive lesion, are treated aggressively, with chemotherapy and surgery. It is estimated that only 30% of women with DCIS will develop invasive breast cancers, thus approximately 70% of patients are being overtreated. In recent studies, we have focused on examining the expression levels of members of the epidermal growth factor (EGF) family in DCIS lesions. There are several members of the EGF family, and two of these members, Amphiregulin and Epiregulin, are induced in early stage hyperplastic lesions. We propose that these factors can drive invasive breast cancers and that these ligands dictate which specific subtype of breast cancer is going to develop. The proposed project will 1) examine signaling pathways activated by these ligands in mammary epithelial cells, 2) determine the effects of overexpressing these ligands on epithelial morphogenesis in three dimensional culture and 3) assessing expression levels of these proteins in normal and DCIS samples obtained from patients. These studies will provide novel biomarkers of early stage breast cancer progression and will lead to novel, less aggressive therapeutic approaches for patients with pre-malignant breast cancers.

Eligible Funding Sources: Merial, NIH, CVM, Skadron Family Fellowship

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Project Title: Determination of release kinetics of therapeutic agents from controlled-release subcutaneous implants
Mentor: Dr. Patrick Redig
Contact: redig001@umn.edu

Project Description: Many therapeutic drugs used in avian medicine require at least daily and sometimes multiple-times daily handling of the patient for administration. This is difficult for owners to do in many cases and stressful to the patient. In wildlife patients, the additional handling can be even more stressful. Sustained-release implants have been used to deliver measured doses of medications over time in some species. Examples in exotic species include Ferrotonin in ferrets (melatonin implants) and contraceptives in many zoological species. We seek to evaluate this methodology in an avian species, looking at the pharmacokinetics of either an antifungal drugs from drug-impregnated implant vehicles or Vitamin K given in a sustained-release formulation. Animals will be implanted and blood samples collected on a scheduled basis to determine blood profiles. Plasma levels will be determined by HPLC.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Clinical Sciences

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Project Title: Molecular Genetic Bases of Disease Traits in Dogs
Mentor: Dr. Ned Patterson
Contact: patte037@umn.edu

Project Description: Breeding practices which select for desirable traits in domestic animal species can inadvertently select for undesirable alleles that increase the prevalence of heritable diseases. A major goal of our canine genetic research group is to determine the genes and alleles that contribute to heritable neurological, neuromuscular and metabolic disorders in certain canine breeds. Our basic hypothesis is that as yet unidentified genes responsible for genetic traits can be identified by a "scan" of the genomes of dogs with a disorder (cases) and control dogs without the disorder with tens of thousands of DNA markers known as SNPs. This genome scan narrows the search for genes that contribute to that particular trait to relatively small chromosomal segments where the significantly different SNP markers are located, that contain relatively few plausible candidate genes. It is then possible to identify the causative mutation itself by sequencing DNA or mRNA from one or more genes in cases and comparing them to control dogs. Any sequence differences (potential mutations) found are then analyzed in larger populations to accurately determine their association with the phenotype, and their frequency in the breed. Traits that could be pursued include peripheral neuropathies (Leonbergers and a number of breeds), urinary stone formation (multiple breeds), hypercalciuria (multiple breeds), diabetes mellitus (Miniature Schnauzers), and idiopathic epilepsy (Australian Shepherds, and other breeds).

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterinary Clinical Sciences

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Project Title: Lipid metabolic pathways in canine hemangiosarcoma
Mentor: Dr. Erin Dickerson
Contact: edickers@umn.edu

Project Description: Canine hemangiosarcoma is a common and highly aggressive, lethal cancer in dogs. These tumors are largely drug resistant, and the outcomes of dogs with this disease are unlikely to improve without a better understanding of its biology and pathogenesis. We recently discovered that hemangiosarcomas process or transport high amounts of lipids and cholesterol, and we have hypothesized that lipid and cholesterol metabolic pathways could be key mechanisms for hemangiosarcoma cellular proliferation and survival. This project is designed to extend these findings by beginning to define the metabolic enzymes and pathways involved, and determine if drug intervention in these pathways inhibits cell survival or proliferation. We will utilize several approaches in a panel of hemangiosarcoma cell lines to establish the role of fatty acid synthesis or fatty acid oxidation in this disease. Expression of key regulatory enzymes will be determined by immunoblotting with potential translation to archived tumor samples. Drug intervention will be used to determine the effect on cell viability and proliferation once involvement of fatty acid synthesis or oxidation pathways are identified.

Eligible Funding Sources: Merial, NIH, CVM, Skadron Family Fellowship, Department of Veterinary Clinical Sciences

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Project Title: Role of immune cells and inflammation in cancer
Mentor: Dr. Bruce Walcheck
Contact: walch003@umn.edu

Project Description: White blood cells (leukocytes) play an important role in preventing the spread of cancer. A specific protein expressed by leukocytes that regulates their function is ADAM17. This protease cleaves receptors from the surface of leukocytes and can prevent them from properly recognizing and killing cancer cells. A research project in my lab will involve investing the function of ADAM17 and leukocytes in killing tumor cells or inducing inflammation, which can promote cancer. Our studies primarily focus on eventual treatments for human cancer, but are also relevant to companion animal health. Specific topics in this line of research will be discussed to determine a good match for the student. I'm also the Director of the NIH T35 training grant for Summer Scholars, and I'm happy to discuss with students the projects of other faculty involved in this training grant.

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterinary Biosciences

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Project Title: Unraveling the genetic basis of susceptibility to recurrent exertional rhabdomyolysis in Standardbred horses
Mentor: Dr. Molly McCue
Contact: mccu0173@umn.edu

Project Description: Breeding practices which select for desirable traits in domestic animal species can result in selection for and even fixation of the causative allele within breeds. A major goal of our equine genetic research group is to determine the genes and alleles that contribute to musculoskeletal, neuromuscular and metabolic traits that have been highly selected for in horses, as well as genes and alleles that cause heritable disorders affecting these same systems in certain breeds. In this case susceptibility to recurrent exertional rhabdomyolysis (RER), a painful heritable muscle disease, in Standardbred horses. To identify the gene or genes responsible for RER susceptibility we have interrogated the genomes Standardbred horses that are known to be RER susceptible or are healthy controls with tens of thousands of DNA markers known as SNPs. This approach has narrowed the possible genomic regions where genes associated with RER susceptibility to several regions encompassing 2-10 megabases of DNA on different chromosomes. To simultaneously and efficiently investigate multiple regions of the genome, we are using next generation sequencing technologies to sequence the entire genome of 5 RER cases and 5 controls. The goal of this summer scholars project is to analyze genomic sequences from horses to discover functional alleles (or mutations) responsible for RER susceptibility and to further investigate the most plausible alleles in a cohort of more than 384 horses to confirm association with the RER phenotype.

Eligible Funding Sources: Merial, NIH, CVM, Department of Veterinary Population Medicine

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Project Title: Protection of beta cell survival in diabetes
Mentor: Dr. Meri Firpo
Contact: firpo001@umn.edu

Project Description: Our preliminary studies with mice fed a high fat diet support the conclusion that beta cell death in diabetes results through a mechanism that can be inhibited. We are using mice and cells in culture to identify inhibitors of beta cell death in wild type and mutant mice with defects in cell death regulation.

Eligible Funding Sources: Merial, NIH, CVM

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Project Title: Diagnostic utility of renal cytology and ultrasound
Mentor: Dr. Leslie Sharkey
Contact: shark009@umn.edu

Project Description: Renal disease is extremely common in dogs and cats, however the diagnostic evaluation of these patients is limited by poor sensitivity of serum biochemical indicators and reluctance to perform biopsy and histopathology due to risk of complications triggering progression of disease. This hampers the otherwise promising potential of using companion animals to model aspects of the etiology, progression, and response to treatment of some human renal disease. Ultrasound imaging and cytology are safe and accessible alternatives, however larger scale studies evaluating their value have not been performed. Our proposal is to use the approximately 200 dogs and cats with renal cytology performed between 2004 and 2013 already extracted from the Veterinary Medical Center data base to evaluate the diagnostic utility of renal ultrasound and cytology and to ultimately correlate this data with serum biochemical data, histopathology, and clinical outcome. Cytology slides have been pulled for review of the following criteria by the student (C. McAloney) and a board certified veterinary clinical pathologist (L. Sharkey): diagnostic yield, normal kidney cells (tubular and glomerular), hyperplasia, inflammation and subtypes, neoplasia and subtypes. Radiographic and ultrasound images will be evaluated by the student and a board certified veterinary radiologist (D. Feeney) for renal size, relative echogenicity of the renal cortex and medulla to the spleen and liver, distinctiveness of the corticomedullary junction, presence or absence of pyelectasia, the renal resistive index, and characterization of the renal surface. For cases in which lymphoma was the cytologic diagnosis (35/200), confirmation of the diagnosis will be performed retrospectively by using archived smears for PCR for antigen receptor rearrangement (PARR). Generic malignant neoplasia diagnoses will also be evaluated by PARR). The data set will be used to establish an estimate of diagnostic yield and accuracy for cytologic diagnoses, to determine if combinations of cytologic and imaging findings improve diagnostic accuracy, and to evaluate imaging and cytologic findings that correlate with clinical outcomes.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Clinical Sciences

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Project Title: Pre-Clinical Development of a new heart valve
Mentor: Dr. Richard Bianco
Contact: bianc001@umn.edu

Project Description: Surgical implantation, echo and angio assessment and pathologic analysis of a new synthetic heart valve.

Eligible Funding Sources: Merial, CVM

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Project Title: Biochemical analysis of membranes induced by bone cement in a caprine tibial defect
Mentor: Dr. Liz Pluhar
Contact: pluha006@umn.edu

Project Description: Masquelet et al. originally described a procedure where large bone defects (up to 25 cm) could be treated using a cement bone spacer to produce an induced membrane The bone cement was removed after 2 months and cancellous bone was grafted into the defect surrounded by the membrane. This technique prevented the resorption of the cancellous bone graft and also improved revascularization of the graft. A similar technique was used in a rabbit model to perform histologic and immunochemical studies of the membranes where measurable levels of BMP-2, VEGF, and TGF-β1 were found. All off these proteins have bone stimulatory properties. VEGF induces angiogenesis and helps to regulate the ingrowth of new vessels to healing bone callus. TGF-β1 stimulates bone metabolism and extracelluar bone matrix synthesis. BMP-2 has a variety of effects including bone induction and generation. We have developed a new goat model of a tibial defect that includes the production of an induced membrane. The goal of this project is to measure the levels of these bone stimulatory proteins in the induced membranes in this goat model.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Clinical Sciences

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Project Title: The role of Thymic Stromal Lymphopoietin (TSLP) in inflammatory diseases of the gastrointestinal tract
Mentor: Dr. Nicholas Robinson
Contact: robin622@umn.edu

Project Description: Gastrointestinal inflammatory diseases in dogs are often closely aligned with similar diseases in humans allowing natural disease and comparative models in animals to have a dual impact of improving veterinary and human disease knowledge simultaneously. The role of Thymic Stromal Lymphopoietin and it’s regulation of a number of effector cells within gastrointestinal disease has recently been highlighted as a critical step in otherwise poorly understood diseases (Noti et al 2013). Natural disease (Inflammatory bowel disease [IBD] and Eosinophilic Esophagitis [EE]) within the dog will be screened for TSLP and evaluated for its role within the currently understood pathogenesis of each disease. The experimentally derived EE models in knockout (SWAP-70) and transgenic (IL-5) mice will allow more mechanistic evaluation of the role TSLP has with effector cells such as eosinophils and others such as basophils. The mouse model of eosinophilic esophagitis will be induced by sensitization with the allergen Ova.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Population Medicine

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 Emerging and Zoonotic Disease

 

Project Title: Vaccine-induced PRRSV-neutralization in swine
Mentor: Dr. Michael Murtaugh
Contact: murta001@umn.edu

Project Description: PRRSV (porcine reproductive and respiratory syndrome virus) causes abortions, weak-born pigs, and polymicrobial respiratory disease in swine. It is the most important swine pathogen globally. Many viral infections are effectively prevented by vaccines that induce high titers of neutralizing antibodies. PRRSV infection is not known to do this and, coincidentally, PRRSV vaccines are incompletely effective. We recently discovered that field virus infection can induce high titers of broadly neutralizing antibodies. In this project, we seek to determine the conditions, if any, under which live, attenuated PRRSV vaccines induce the production of broadly neutralizing antibodies. Serum will be collected from pigs with histories of vaccine exposure to evaluate the overall anti-viral humoral reactivity and neutralizing titer.

Eligible Funding Sources: SDEC, Department of Veterinary Biosciences

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Project Title: Maternal immunity to enteric viral infection
Mentor: Dr. Michael Murtaugh
Contact: murta001@umn.edu

Project Description: Newborn animals and humans are at high risk of devastating infections due to the lack of a well-developed immune system. Hence, transfer of immunity from immune mothers via colostrum and milk is essential. It is challenging to protect newborns from newly emerging diseases due to the fundamental lack of knowledge of key protective mechanisms and target antigens on novel pathogens. We are characterizing maternal immunity to a new swine pathogen, porcine epidemic diarrhea virus (PEDV), with particular attention to antibody-mediated immune protection and assays that detect and predict protection.

Eligible Funding Sources: SDEC, Department of Veterinary Biosciences

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Project Title: Novel Essential Regulator of Staphylococcus aureus
Mentor:
Dr. Yinduo Ji
Contact: jixxx002@umn.edu

Project Description: Staphylococcus aureus is an important pathogen of animals and humans. This organism is able to cause pneumonia in healthy infants and children, people with cystic fibrosis, and patients in intensive care wards, and cow mastitis. The continued emergence of multiple antibiotic-resistant strains of S. aureus, especially methicillin-resistant isolates (MRSA) and vancomycin intermediate-resistant isolates, has caused serious public health concern and considerable international pressure to limit antimicrobial therapy. The ability of S. aureus to cause such severe illness is partially due to its expression of various factors that enable the bacteria to survive and internalize into host cells and evade host immune systems. This organism has evolved a series of two-component signal transduction systems (TCS) in order to sense its immediate surroundings and to modulate cellular responses and the expression of virulence and essential genes. Our long-term goals are to elucidate the molecular and cellular mechanisms controlling the expression of genes involved in pathogenesis. The objective of this project is to identify and determine the role of different regulators and their target genes in anti-phagocytosis using health human blood and cell line.

Eligible Funding Sources: Department of Veterinary Biosciences

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Project Title: Influence of route-of-infection in the development of CWD prion strains
Mentor: Dr. Davis Seelig
Contact: dseelig@umn.edu

Project Description: Chronic Wasting Disease (CWD) is a naturally-occurring, horizontally-transmitted prion disease of white-tailed deer, elk, mule deer and other cervids. Like all prion disease, CWD results from the conversion of the normal prion protein (denoted PrPC) to a pathologic, misfolded isoform (denoted PrPD). Following its initial conversion, PrPD progressively accumulates in a number of tissues, the most clinically significant being the central nervous system (CNS) which ultimately results in terminal, neurologic disease. Like other prion diseases, CWD is characterized by the presence of a number of unique “strains,” which are unique PrPD variants that result in distinct clinical and neuropathologic disease profiles. Moreover, while CWD is the prototype of horizontal prion infection, the process(es) by which it has acquired its high degree of horizontal infectivity are not well understood. In our laboratory, a central hypothesis proposes that misfolded prions are not a single species, but are rather a dynamic and evolving collection of unique strains, each of which are capable of novel patterns of pathology, infectivity, and clinical disease. Moreover, we hypothesize that route-of-infection (ROI) plays a pivotal role in strain selection and, may ultimately participate in the process of conferring infectivity to misfolded proteins. The aim of the proposed project is to characterize the role that ROI plays in the generation of unique prion strains in a rodent model of CWD. To do so, we are comparing the strain-enciphered features from two groups of differentially-infected (oral and intraperitoneally) infected mice. Unique strains will be identified by several, well-characterized, strain characterization tools, including: 1) lesion profiling and 2) immunohistochemical PrPD mapping (“PrPD profiling”). In these mice, we hypothesize that orally-infected mice will develop unique forms of murine CWD characterized by a clinical, neuropathologic, and biochemical phenotype distinct from parenterally-infected mice (i.e. a unique prion strain). Resultant from this work, we will be able to evaluate our hypothesis that ROI is a significant determinant in the creation of unique CWD strains and develop fundamental insights into the manner by which a misfolded protein acquires infectivity.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Clinical Sciences

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Project Title: Transmission, control and elimination of influenza virus in pigs
Mentor: Dr. Montse Torremorell
Contact: torr0033@umn.edu

Project Description: The goal of the project is to elucidate mechanisms and routes of transmission of influenza virus in pigs and to evaluate strategies to prevent, control and eliminate influenza virus in pig populations.

Eligible Funding Sources: SDEC, Department of Veterinary Population Medicine

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Project Title: Epidemiologic description of endemic Porcine Epidemic Diarrhea (PED) in China
Mentor: Dr. Bob Morrison
Contact: bobm@umn.edu

Project Description: United States is experiencing epidemics of PED virus throughout the swine industry. The virus swept through a cluster of Oklahoma herds in June, then hit North Carolina and recently has been spreading in central Iowa. After infection, a sow herd can expect to wean no pigs for approximately 4-5 weeks. Veterinarians are attempting to eliminate the virus from infected herds but there is major concern that the virus will remain endemic in some sow herds. The virus is 99.9% similar to the PED virus that swept through the Chinese swine industry in 2010-11. Many Chinese sow herds are endemically infected and live with sporadic outbreaks of piglet and nursery pig diarrhea. There is no published description of the endemic state of infection that we in United States can learn from. The objective of this project is to conduct an epidemiologic description of endemic PED virus. The student will analyze historical production records from a sample of Chinese sow farms. In addition, the student will observe endemic PED and characterize the age of litters affected, duration of clinical signs, and case fatality rate.

Eligible Funding Sources: SDEC, Department of Veterinary Population Medicine

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Project Title: Porcine gut microbiota in a neonatal pig model
Mentor: Dr. Maria Pieters
Contact: piet0094@umn.edu

Project Description: In our research group we have studied the effect of commensal gut microbiota or commercial probiotic products in experimental challenge models, using Porcine Reproductive and Respiratory Syndrome Virus and Mycoplasma hyopneumoniae infections. We have demonstrated potential implications of commensal gut microbiota in the pig’s immune response, not only at the local level, but also at the systemic level in a 6-week old piglet model. However, little is known about the effect of gut microbiota in a very young pig model (<7 days of age). Therefore, this investigation consists of a series of field studies directed at evaluating the effect of porcine gut microbiota on a neonatal pig experimental model. Specifically, we aim at evaluating the implications of feed-back practices on the health status and performance of young pigs. In today’s swine production conditions the use of feed-back material has become a common practice, especially in the last months due to the emergence of viral pathogens that can greatly affect swine health and production. Nevertheless, many practices used to mitigate disease have not been widely tested and are usually employed as extrapolations that have resulted successful for other situations, or even other pathogens. Thus, we are proposing this study to explore the effect of feed-back practices on the overall suckling piglet health. This investigation will combine work in the field and the research laboratory, giving the student the opportunity to perform hands-on applied research in both settings. Briefly, studies of this investigation will be performed in swine farms of high health status, using large groups of pigs. The field aspects of this study imply administration of the inoculum material, collection of clinical specimens, observation of clinical signs, and measurement of production parameters. The laboratory aspects of this investigation imply sample processing and submission and the potential to get involved in molecular analysis of clinical specimens. Results obtained from this study will serve as preliminary data for the design of larger studies looking into specifics of the piglet’s immune response and its relationship with the resident microorganisms of the gut. Also, this data could be used to illuminate the mechanistic effects of protection observed in similar approaches employed in human medicine.

Eligible Funding Sources: SDEC, Department of Veterinary Population Medicine

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Project Title: Leptospirosis in livestock from farms and rural villages in Southern Chile
Mentor: Dr. Claudia Munoz-Zanzi
Contact: munozzan@umn.edu

Project Description: The objective of the study is to describe prevalence, serovar distribution and risk factors associated with leptospirosis in livestock from 4 rural villages (~120 households) and 4 farms communities (~120 households) in southern Chile. Data available include MAT results, animal information, household characteristics, spatial variables, climate variables, and Leptospira presence in environmental samples and other species.

Eligible Funding Sources: TBD

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Project Title: Disease ecology-fieldwork and analysis
Mentor: Dr. Meggan Craft
Contact:
craft@umn.edu

Project Description: Two research opportunities are available to develop research projects on disease transmission within animal populations. The goal of the research would be to understand the spread and control of infectious diseases in wild or domestic animal populations. Fundamental research questions of interest include: (i) How are pathogens that infect multiple animal species maintained? and (ii) How does host social structure and movement affect the spread of infectious disease? This would likely involve testing hypotheses regarding infectious disease dynamics by using real world data in mathematical models. Mathematical models are critical tools in the fight against infectious diseases—they allow for virtual experiments that would otherwise be unethical or unachievable in the real world. Model output can be used to predict disease dynamics, and can guide and prioritize future disease monitoring and disease control strategies. Projects could involve fieldwork to collect data relevant to infectious disease transmission.

Eligible Funding Sources: Department of Veterinary Population Medicine

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Project Title: Effect of vitamin D on multiple sclerosis
Mentor: Dr. Julie Olson
Contact: jkolson@umn.edu

Project Description: Multiple sclerosis (MS) is a demyelinating disease associated with an inflammatory immune response in the central nervous system (CNS). Patients are usually diagnosed with the disease in their 20’s and 30’s but the causative agent has not been determined. Epidemiological studies have suggested that environmental factors that a person encounters during the first 15 years of life play a role in development of disease. Low levels of vitamin D have been associated with increased incidence in MS. A virus infection during childhood has been suggested to begin the disease process, although the exact virus has not been identified. We propose that there may be a combination of these environmental factors that leads to development of demyelinating disease. Vitamin D3 has been shown to have immunomodulatory properties which can reduce pro-inflammatory immune responses. Viruses have been suggested to initiate autoimmune diseases through bystander damage or through bystander activation of immune cells during the virus infection. We propose that low levels of vitamin D at the time of a virus infection in the CNS may lead to a pro-inflammatory immune response that promotes the development of demyelinating disease. Theiler’s murine encephalomyelitis virus (TMEV) infection of susceptible mice leads to the development of a chronic progressive demyelinating disease associated with an inflammatory immune response in the CNS. TMEV- induced demyelinating disease will be used to determine how vitamin D3 levels affect the immune response during virus infections and how this immune response affects development and progression of demyelinating disease. Mice will be fed high vitamin D3 diet prior to and during TMEV infection and the effect of vitamin D3 on both the innate and adaptive immune response will be analyzed since both responses have been suggested to contribute to the development of demyelinating disease following TMEV infection. The results from these studies will determine whether high levels of vitamin D3 can promote an immune response that does not lead to the development of demyelinating disease following a virus infection. These studies may provide new perspectives on prevention of MS as well as contribute to the ongoing studies examining how vitamin D3 may be used as a therapy to reduce progression of disease.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Biosciences

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Project Title: Knowledge and risk percetion about rodent-borne zoonosis
Mentor: Dr. Claudia Munoz-Zanzi
Contact: munozzan@umn.edu

Project Description: Survey analysis to describe knowledge and risk perception about leptospirosi and hantavirus among head of households in rural and slum communities from southern Chile. n = 180 surveys.

Eligible Funding Sources: TBD

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Project Title: Creating a framework for rapid and effective fish health management in Minnesota
Mentor: Dr. Nicholas Phelps
Contact: phelp083@umn.edu

Project Description: Rapid detection and evaluation of fish kills (a localized die-off of a fish population) is an essential component of monitoring the health of delicate aquatic ecosystems and valuable fisheries. This is particularly critical in Minnesota, where a thriving wild baitfish industry, active re-stocking program, and a vast network of recreational activity could rapidly disseminate disease regionally and nationally should a problem remain undiagnosed and unchecked. This risk was highlighted following a 2003 mortality event of muskellunge in Lake St. Clair, Michigan. A then-unknown virus was isolated, however little follow up investigation or communication was performed. Two years later, the same virus, viral hemorrhagic septicemia virus (VHSV-IVb), was identified during another mortality event in the same species and body of water. The virus has since spread throughout the Great Lakes region, resulting in the loss of millions of fish and an unprecedented regulatory response on the aquaculture industry. This case provides a poignant illustration of the need for the development of timely, proactive approaches to managing aquatic ecosystem health in Minnesota. Fish kills in Minnesota are unfortunately routine events and rarely investigated. The lack of investigation is due to a variety of factors, but often decisions are made based on visual observation and deemed the result of commensal bacteria, high temperatures, or low oxygen. While possible, there are no doubt other threats being overlooked. When fish kills are investigated, few data standards exist and there is very little inter-agency cooperation or discussion. The lack of standardization makes comparisons or long-term monitoring impossible to accomplish in a timely manner, rendering existing data less than useful to assist with science-based management. It is clear that Minnesota is in need of a comprehensive fish health risk assessment and management program, and this is the overarching goal for this and other ongoing projects. The focus of this project will be to create a framework to rapidly and effectively investigate fish kill events. This will include the development of reporting and investigation protocols that lead to the collection of standardized data, which can be used for real-time risk assessment aimed at supporting science-based management. As a proof of concept, at least two fish kill events will be investigated during the project in collaboration with the Minnesota Veterinary Diagnostic Laboratory and Department of Natural Resources to evaluate the framework.

Eligible Funding Sources: Department of Veterinary Population Medicine

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Project Title: Application of a novel method for the non-invasive screening for tuberculosis among free-living primates
Mentor: Dr. Srinand Sreevatsan
Contact:  sreev001@umn.edu

Project Description: A recent diagnosis of infection with a novel organism of the Mycobacterium Tuberculosis Complex (MTC) was made in a free-living chimpanzee in Tai National Forest, Ivory Coast(Coscolla et al., 2013). The MTC consists of pathogenic mycobacteria that cause tuberculosis, such as Mycobacterium tuberculosis, M. bovis, and M. africanum. This is the first report of tuberculosis in a free-living great ape, although tuberculosis has been observed in monkey populations across Africa and southeast Asia, particularly those in high contact with humans (Keet, Kriek, Bengis, Grobler, & Michel, 2000; Tarara, Suleman, Sapolsky, Wabomba, & Else, 1985; Wilbur et al., 2012). Unfortunately, our knowledge of the extent to which MTC infections impact great ape (and monkey) populations has been limited by challenges in detecting MTC infection in free-ranging primates. The diagnosis of MTC infection in primates, which requires multiple diagnostic modalities such as demonstration of tissue lesions, host immune responses, or culture of the organism, is not feasible in free-ranging species given the need for handling and anesthesia. Thus, detection has been limited to post-mortem diagnosis, at which time transmission of tuberculosis may be well advanced through a social primate group. Our research group has recently validated the use of a non-invasive fecal PCR for the detection of tuberculosis infection in free-living primates. The proposed project is the application of this novel approach to screen fecal samples collected from Gombe National Park chimps and baboons. This study will be the first ever non-invasive tuberculosis screening of a free-living population of primates.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Population Medicine

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Population Systems

 

Project Title: Simulation modeling of foodborne pathogen transmission, sampling strategies, and antimicrobial resistance (multiple projects)
Mentor: Dr. Randall Singer
Contact: rsinger@umn.edu

Project Description: In this project, you will learn to develop simulation models using programs such as Microsoft Excel or modeling software such as STELLA. There are several questions that can be addressed in these models. In one type of project, the student can assess the optimal sampling strategy for detecting the diversity of antimicrobial resistance patterns that exist on a farm or in a retail meat sample. This type of model will aid in the development of on-farm and retail surveillance systems such as NARMS (I collaborate with FDA and USDA). In another project, the student can choose to develop simulation models predicting the spread of antimicrobial resistance on the farm. Finally, the student can help build models of the poultry production system that will aid in the prediction of Campylobacter or Salmonella being transmitted to humans through the consumption of poultry products.

Eligible Funding Sources: CVM, Department of Veterinary Biosciences

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Project Title: Finding the unknown: what is the scope of multidrug resistance in Minnesota ecosystems?
Mentor: Dr. Tim Johnson
Contact: joh04207@umn.edu

Project Description: Antibiotic resistance is a global threat to the treatment of human and animal infections. We are now fully aware that resistance among bacterial pathogens is increasing at alarming rates, and these "superbugs" pose threats to hospitals and other health care settings. However, we do not fully understand the reservoirs of antibiotic resistance in healthy humans and the surrounding environment. If we are going to stop the spread of antibiotic resistance in bacterial pathogens, it is imperative that we better understand these reservoirs. The purpose of this project is to search for bacterial plasmids that enable multidrug resistance in Minnesota ecosystems. Using a novel approach, you will collect soil and water samples from different parts of the state, isolate plasmids from these samples, and use molecular biology to identify and isolate multidrug resistance-encoding plasmids. Then, genomics will be applied to understand the diversity of these genetic elements in the environment, and their relationship to plasmids in medically important pathogens.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Biosciences

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Project Title: Investigating the relationship between passive transfer and response to early vaccination in Holstein dairy calves
Mentor: Dr. Sandra Godden
Contact: godde002@umn.edu

Project Description: Passive transfer of maternal immunity in newborn calves is achieved by suckling of immunoglobulins/antibodies in colostrum, the first milk produced by cows following the birth of the calf. While there is a substantial body of knowledge concerning the importance of passive transfer there is still much to learn about the variability in specific antibodies to important pathogens among individual colostrums and about the interaction of colostral antibodies with other management tools for calf health such as vaccination. In this study we will examine specific titers of antibodies in colostrum, in the serum of calves following passive transfer from the colostrum and will monitor the rates of disappearance of the maternal antibodies from the bloodstream of the calf in an attempt to predict the impact of those antibodies on responses to vaccinations. We will compare responses in calves fed maternal colostrum to those fed a standardized commercial colostrum product.

Eligible Funding Sources: Department of Veterinary Population Medicine

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Project Title: Case Studies in Biodiversity and Health
Mentor: Dr. Dominic Travis
Contact: datravis@umn.edu

Project Description: Ecosystem Health recognizes the inherent interdependence of the health of humans, animals and ecosystems and explores the perspectives, theories and methodologies emerging at the interface between ecological and health sciences (Wilcox, 2004). Wilcox divides ecosystem health into five main pillars: Conservation medicine, global change, human health, and integrated studies in ecology, health, and sustainability - all themes that form a collaborative union between human, animal, and environmental health. Central to all of these concepts is the idea of biodiversity - it is the underpinning of sustainable life on earth and provides innumerable 'ecosystem services' to humans along the way. I have a grant from the UMN Institute on the Environment (IonE) to explore the relationship between biodiversity sustainability and the health of humans and animals. The project is aimed at achieving three goals: 1) create a catalogue of case studies that will populate a website; 2) create a umn faculty interest group in this area with representation from the academic health center and vast network of IonE; 3) engage interest group to prioritize teaching and research opportunities/needs in this area. An appropriate summer scholar - or two - will help me achieve these three goals and take ownership of the development of one of more case studies, depending upon complexity and energy. The outputs will be 1) a report to IonE and fully developed case studies with options for developing them into full research proposals, 2) a poster created from case study, 3).....if appropriate, this project could be good for someone intending to do an MPH or interested in further graduate studies in ecosystem health.

Eligible Funding Sources: Department of Veterinary Population Medicine

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Project Title: Amphibian disease risk in Minnesota
Mentor: Dr. Dominic Travis
Contact: datravis@umn.edu

Project Description: Amphibians are in decline worldwide. One of the drivers of this decline is the presence of infectious diseases, in particular Chytrid fungus and Ranavirus. There have been some studies done in specific areas in Minnesota that show the presence of these two pathogens in some of the local species of frogs (Uyehara, I. K., et al, 2010.; Wolff, B.G., et al, 2012). However, these studies are limited, and they entailed the euthanasia of the frogs in order to find the pathogens. As part of a larger BioDiscovery project, MN Zoo researchers are surveying frog species and their abundance across a variety of pond habitats on zoo site and across seasons (spring, summer, and fall). This ongoing work offers an opportunity to study the epidemiology of two important amphibian diseases (Chytrid fungus and Ranavirus) across Minnesota seasons and habitats. We propose a non-lethal, longitudinal survey of these two pathogens across frog species and habitats in coordination with the ongoing BioDiscovery project of the MN Zoo. The goals are to assess prevalence of these pathogens across species of frogs, season, and habitat. The methods will include capturing frogs and collecting morphological measurements, skin and cloacal swabs several times throughout the spring, summer and fall months; water quality testing; data management and processing, and basic descriptive statistics. Ultimately, the project will be an initial step in describing the epidemiology of Chytrid fungus and Ranavirus in Minnesota frogs, providing baseline data for future studies.

Eligible Funding Sources: Department of Veterinary Population Medicine

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Project Title: An evaluation of an alternative treatment modality for digital dermatitis lesions in dairy cows
Mentor: Dr. Gerard Cramer
Contact: gcramer@umn.edu

Project Description: Currently, digital dermatitis (DD) is the most common cause of lameness in dairy cows and in turn a cause of reduced dairy cattle welfare. Recent work has show that Treponema spp bacteria are a causative agent for DD and that bacteria invade deep into the epidermis at the time of infection. Typical treatment for DD consists of an antibiotic applied topically as paste or bandage. This single treatment of a topical antibiotic has been shown to be effective but with only one treatment, recurrence is common. Due to concerns related to appropriate antibiotic use and food safety, several alternative treatments for DD exist in the market place. Unfortunately very few of these products have been formally evaluated to determine efficacy and safety. One of more interesting products that has recently been introduced has been a product called Mortella Heal. This product consists of a plastic bandage combined with a pressure pad and bandage that is applied for 7-10 days to allow the cow’s natural body defenses to heal the lesion. The goal of the project would be to evaluate the safety and long term efficacy of Mortella Heal.

Eligible Funding Sources: Department of Veterinary Population Medicine

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Project Title: An evaluation and description of different hoof trimming methods practiced by professional hoof trimmers in dairy cows
Mentor: Dr. Gerard Cramer
Contact: gcramer@umn.edu

Project Description: Lameness in dairy cows is a painful and costly disease that affects the dairy industry from animal welfare perspective and from a productivity perspective. Functional hoof trimming is considered one of the keys to a lameness prevention program. The role of functional hoof trimming is to restore balance of weight bearing between the 2 hooves. Currently, a variety of methods are used and taught for functional hoof trimming. Unfortunately there is a paucity of data that describes and supports the different trimming methods used by both professional and on farm hoof trimmers. Furthermore, recent evidence suggests that there is variation in the size of anatomical structures in the hoof. The goal of this project is to describe and add scientific evidence to the discussion about proper hoof trimming techniques in the dairy industry.

Eligible Funding Sources: Department of Veterinary Population Medicine

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Project Title: A Descriptive Analysis of Wildlife Rehabilitators in Minnesota: Awareness and prevention of occupational and zoonotic risks
Mentor: Dr. Michelle Willette
Contact: wille203@umn.edu

Project Description: Emerging and re-emerging zoonotic infectious diseases such as West Nile virus, avian influenza, and monkey pox have focused attention on the human-animal interface. Most of these emerging zoonotic diseases have wild animal reservoirs. Currently there is no comprehensive system for monitoring wildlife health in North America. However, there are several thousand permits issued for wildlife rehabilitation, and it is estimated that more than 500,000 terrestrial and marine animals are seen at wildlife centers on an annual basis. Due to their frequent and direct contact with a variety of sick animals, wildlife rehabilitators represent a significant occupational zoonotic disease risk. In a national survey of wildlife rehabilitators (2008), less than 40% of respondents indicated they had any medical background. The state of Minnesota currently permits 55 individuals or organizations to rehabilitate wildlife under the Department of Natural Resources. Roughly 60% of permit holders reside in the seven county metro area. Between 8,000 and 9,000 animals are handled by rehabilitators each year; the Wildlife Rehabilitation Center in Roseville, MN and The Raptor Center (TRC) at the University of Minnesota account for nearly 70% of all animals. Nearly 200 different species of animals are rehabilitated in an average year. On average, one-third of all animals rehabilitated each year are cottontail rabbits, gray and fox squirrels, and raccoons; the remaining two-thirds are mainly small birds. Of all animals received by individual rehabilitators, about 50% are ultimately released back to the wild, 25% die, 12% are euthanized, and the remainder transferred to other rehabilitation facilities. In preparation for a national survey, we propose to conduct a pilot survey of wildlife rehabilitators in Minnesota in 2013. 1. Descriptive analysis of the species, numbers of animals, and outcomes presented for rehabilitation. This information will be obtained from annual permits submitted to the Minnesota Department of Natural Resources. 2. Literature review to identify zoonotic diseases of concern in these species. 3. Identify risk factors for acquisition of these zoonoses. 4. Based on the above information, conduct a written/phone survey of wildlife rehabilitators. Information collected may include: a. Information on organization/rehabilitator b. Educational background of rehabilitator c. Knowledge of occupational and zoonotic disease risks d. Known incidence of zoonotic disease at rehabilitation center (2013) e. Resources available to screen wildlife for disease/toxicants f. Protocols in place to prevent occupational and zoonotic disease 5. Validate pilot survey.

Eligible Funding Sources: Department of Veterinary Population Medicine
 
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Project Title: Use of whole genome sequences to unravel the genetic basis altered locomotion in horses
Mentor:
Dr. Molly McCue
Contact:
mccu0173@umn.edu

Project Description: Breeding practices which select for desirable traits in domestic animal species can result in selection for and even fixation of these desirable traits and the underlying causative allele within a population. In the horse this process has lead to distinct alternate patterns of locomotion or ‘gait’ with in particular horse breeds; a phenomenon unique among domestic animals. Our recent work has identified a single mutation in the DRMT3 gene that is permissive for alternate gaits in the domestic horse. While the presence of this mutation is necessary to perform alternate gaits; it does not explain the specific gait performed by a breed. The pace, a two beat lateral gait, is one example of an alternate gait that is not explained fully by the DRMT3 mutation. Using genome-wide association analysis, we have mapped the genetic basis of pace to three regions of the genome and identified several putative functional loci using variant discovery in Standardbred pacers and trotters. These data will be used to design a custom genotyping assay to simultaneously genotyped ~400 Standardbred horses for >400 single nucleotide polymorphisms with the goal of identifying the allele(s) underlying pace. Multiple comparisons of the allele frequencies of each of these SNP markers can then be made across these populations (i.e.horses that pace vs horses that trot) to identify the markers most highly associated with the pace phenotype. Once these alleles have been indentified their relative impaction on the expression of the pace phenotype will be determined through statistical modeling. The goal of this summer scholars project is to analyze genomic sequences from horses to discover functional alleles (or mutations) responsible for traits of interest.

Eligible Funding Sources: Department of Veterinary Population Medicine


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Project Title: Use of whole genome sequences to define the genetic basis of performance traits in Quarter Horses
Mentor:
Dr. Jim Mickelson
Contact:
micke001@umn.edu

Project Description: Breeding practices which select for desirable traits in domestic animal species can result in selection for and even fixation of the causative alleles within breeds, or subpopulations within a breed that are selected for different performance traits. A major goal of our equine genetic research group is to determine the genes and alleles that contribute to musculoskeletal, neuromuscular and metabolic traits that have been highly selected for in horses; in this case the sprinting ability of racing class of Quarter Horses, and the muscling and disposition of the halter class of Quarter Horses. Our basic hypothesis is that as yet unidentified genes responsible for these performance traits can be identified by interrogation of the genomes of many Quarter Horses of various performance types with tens of thousands of DNA markers known as SNPs. This approach has identified regions of the equine genome where racing and halter horses differ significantly in genetic marker frequencies. The result is the narrowing of possible genomic regions where genes likely responsible for these differences between populations to several regions encompassing 2-10 megabases of DNA on several chromosomes. To simultaneously and efficiently investigate multiple regions of the genome, we are using next generation sequencing technologies to sequence the entire genome of racing and halter horses. The goal of this summer scholars project is to analyze genomic sequences from horses to discover functional alleles (or mutations) responsible for these traits ability and to further investigate the most plausible alleles in a cohort of more than 384 horses to confirm association with the racing and halter phenotypes.

Eligible Funding Sources: Merial, CVM, Department of Veterinary Biosciences

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Project Title: Acupuncture to improve lameness in cattle
Mentor:
Dr. Riki Sorge
Contact:
sorge@umn.edu

Project Description: Acupuncture has been used for thousands of years in Easter Medicine and it has been said to be useful for the induction of analgesic effects. However, the usefulness of acupuncture for treatment of disease or analgesia has been discussed immensely and applied data for its use in livestock medicine are still sparse. The use of medication in production animals is always associated with withhold times. Acupuncture or acupressure generally do not introduce drugs and therefore, withhold time would not need to be considered. Lameness is a common disease in cattle and the majority of cattle lameness is due to painful lesions in the hind feet of cattle. The objective of this study is to assess if acupuncture improves lameness severity in cattle compared to sham acupuncture. We hypothesize that acupuncture will improved the gait score of cattle compared to controls.

Eligible Funding Sources: Department of Veterinary Population Medicine

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Project Title: Developmental aspects of the turkey muscle transcriptome.
Mentor: Dr. Kent Reed
Contact: reedx054@umn.edu

Project Description: The transcriptome represents the collection of gene transcripts present in a sampled tissue or cell. Characterization of the changes in transcript representation through time can elucidate genes important in tissue development and provide important biomarkers for key developmental stages. As part of the turkey genome sequencing project we have created and sequenced RNA libraries derived from 17 tissues collected from male and female birds at weekly intervals from day of hatch through 4 weeks of age. Over 700 individual libraries were sequenced on the Illumina HiSeq1000 to generate approximately 10M reads per library. Analysis of this data has identified sets of genes which are developmentally modulated in each tissue. The objective of the proposed study is to use the compiled list of differentially expressed muscle genes to validate and investigate gene networks in developing turkey muscle. The student will develop a testable hypothesis based on this preliminary data and collect data to test their hypothesis.

Eligible Funding Sources: Department of Veterinary Biomedical Sciences

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Project Title: Veterinary Role in Public Health Education: Focus on Tickborne Diseases
Mentor: Dr. Jenna Bjork, Epidemiologist, Vectorborne Diseases Program, Minnesota Department of Health

Project Description: The Minnesota Department of Health Vectorborne Diseases Program is seeking a Summer Scholars student to participate in the following project during the summer of 2014. The student will work closely with MDH Vectorborne Disease epidemiologists to develop surveys that will be used to better understand the role of veterinarians in health education for the general public. In particular, the goal for these surveys is to help characterize the knowledge, attitudes, and behaviors of veterinarians in Minnesota regarding tickborne diseases and human health. Results from these surveys will guide the development of educational materials that may be utilized by veterinarians for the prevention of tickborne disease and promotion of human health. In addition to the primary project, the student will also gain hands-on experience with fieldwork involving tick collection efforts around the state. Tick surveillance is an important aspect of the MDH Vectorborne Diseases Program, allowing us to better understand the diversity and prevalence of various tickborne disease agents within the Minnesota landscape. The primary project, fieldwork experience, and any other supplemental activities provided by MDH will offer the Summer Scholars student a great opportunity to apply his or her skills in the field of veterinary public health.

Eligible Funding Sources: TBD

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Project Title: Equine West Nile virus Long Term Outcomes
Mentor: Dr. Larissa Minicucci
Contact: minic001@umn.edu

Project Description: In 2002, Minnesota experienced a significant outbreak of West Nile virus in horses with almost 1000 cases reported to the Minnesota Board of Animal Health. Roughly 30% of the horses in this initial outbreak died as a result of their illness. The human literature has documented some long-term effects of this disease including fatigue, memory loss, and weakness when individuals were re-evaluated a year later. No information is currently available about the long term sequelae of West Nile virus infection in horses. This project would aim to evaluate potential long term effects experienced by horses in this original cohort through a follow-up phone survey of horse owners. In addition to physical signs, behavior, utility, and owner safety aspects will be assessed.

Eligible Funding Sources: TBD

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Project Title: Minnesota Moose Mortality Study – Anesthesia and Liver Datasets
Mentor: Dr. Michelle Carstensen, Wildlife Disease Biologist, Minnesota DNR

Project Description: The Minnesota moose population has been rapidly declining and a mortality study has been initiated by the Minnesota Department of Natural Resources (DNR) to better assess potential causes. As part of this and other studies, moose have been anesthetized, fitted with collars, and samples and measurements have been taken during animal processing. Various anesthetic protocols have been used with varying success. A research project related to this larger study would evaluate effects of different anesthetic protocols on variables such as time to effect, body temperature, recovery time, and capture-associated complications with the goal to make recommendations for appropriate anesthesia protocols. An additional research project would look to determine correlations between liver pathology scores and serum chemistry values for liver enzymes to determine if a predictive model can be developed for liver damage based on serologic data. Data has been collected from moose mortalities and hunter harvested samples. A student on this project would work directly with DNR wildlife biologists and technicians.

Eligible Funding Sources: TBD

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