Faculty Research Projects
2009 Graduate Faculty Projects
Please check back. Faculty research projects are continuously added as they are submitted.
Project Title:CNS sites involved in long term blood pressure regulation
PI (faculty) contact:John Collister
Department:Veterinary & Biomedical Sciences
Room number:295G
Phone number:6-1206
E-mail: Colli066@umn.edu
List names of co-PI’s with affiliation:
Description:Chronic blood pressure regulation and the pathogenesis of hypertension are still not fully understood despite years of research. Recent evidence suggests that certain brain nuclei are involved in the long term actions of circulating hormones as well as containing osmosensitive cells. These areas of the brain lack the normal blood brain barrier and therefore circulating substances can access these sits and act as signals for further neural processing. Our lab focuses on understanding the role of these sites in the long term actions of the hormone, Angiotensin II, and the salt sensitivity of arterial pressure. We are currently examining the role of the median preoptic nucleus, a relay site from projections of the subfornical organ. By utilizing the techni ques of electrolytic or
chemical lesion, we can understand the role of this brain nucleus in the long term actions
of angiotensin II. Electrolytic lesion destroys the area, whereas chemical lesion leaves
fibers of passage intact. We use chronically instrumented rats in which we can measure
blood pressure continuously for up to 6 months via radiotelemetry. Additionally, we can
examine the hemodynamic basis of our results observed from our treatments by
simultaneously measure cardiac output in these animals as well.
Project Title: Use of a production region model for evaluating airborne spread of porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae and protocols of biosecurity.
PI contact: Scott Dee
Department: VPM
Room number: 385C
Phone number: 5-4786
E-mail: deexx004@umn.edu
Co-PI: John Deen, VPM
Description: This is an ongoing project in its third and final year. Students will get the opportunity to work in the Swine Disease Eradication Center Production Region model and evaluate the airborne spread of 2 economically significant agents of swine and test biosecurity protocols to reduce this risk. This model attempts to emulate a “neighborhood” of swine production and involves a cluster of 4 buildings, each representing a farm. Skills to be gained include how to conduct applied research trials, experience in managing nursery and finishing swine, collection of various samples (air, swine sera, fomite/personnel swabs, etc) , analysis of meteorological data collected during periods of airborne spread of pathogens and exposure to two different methods of filtering incoming air: mechanical filters and antimicrobial filters. Students will gain access to the data from years 1 and 2 of the trial and work with a team of researchers committed to serving the swine industry through a better understanding of infectious disease aerobiology.
Project Title: Does Heat-Treatment of Bovine Colostrum Affect Colostral Leukocyte Activity?
PI (faculty) contact: Dr. Sandra Godden
Department: VPM
Room number: A320 VTH
Phone number: 612-625-8177
E-mail: godde002@umn.edu
List names of co-PI’s with affiliation: Dr. Tom Molitor
Description: We have developed a method to heat-treat bovine colostrum to reduce calfhood exposure to pathogenic bacteria. However, there is some question as to whether the heat-treatment process will denature colostral leukocytes. Maternal leukocytes, found naturally in colostrum, are absorbed into the calf’s circulation. Though their function is not yet well understood, it is thought that they may serve to stimulate development of the calf’s own acquired immune system. If this is true, then it might be detrimental to calf health if these cells were denatured during the heat-treatment process. A preliminary study showed that there was no difference in the number of intact leukocytes measured in raw vs heat-treated colostrum. However, that study failed to investigate if these intact cells were, in fact, functional.
The objective of this study will be to investigate if heat-treatment of bovine colostrum affects colostral leukocyte activity. Paired samples of raw and heat-treated colostrum will undergo in vitro testing to quantify activity of lymphocytes, natural killer cells, neutrophils and macrophages. The student’s time will be split between on-farm and in-lab activities. Results will be reported at one or more dairy continuing education meetings (e.g. American Association of Bovine Practitioners) and published.
Project Title: Utilizing Reverse Vaccinology to Identify Vaccine Candidates Against Escherichia coli Causing Post-Weaning Diarrhea in Pigs
PI (faculty) contact: Timothy Johnson
Department: Veterinary and Biomedical Sciences
Room number: 301B
Phone number: 626-2542
E-mail: joh04207@umn.edu
List names of co-PI’s with affiliation: Richard Isaacson, UMN, VBS
Description: Post-weaning diarrhea (PWD) causes significant morbidity and mortality towards pigs, and therefore results in significant annual losses to the swine industry. The overall goal of this project is to identify suitable vaccine candidates that might be used to prevent porcine post-weaning diarrhea. To do so, a global “reverse vaccinology” approach is being used. To enable this approach, we have completed the first genome sequence of an enterotoxigenic Escherichia coli strain implicated in porcine PWD. A computational “reverse vaccinology” approach has been employed in an effort to identify and characterize suitable vaccine candidates from our genomic sequence. Our computational approach has identified 50 genes representing the most suitable vaccine candidates, based upon their predicted protein characteristics. This Summer Scholars project will assess the prevalence of these genes among 100 porcine E. coli strains implicated in PWD, 100 porcine E. coli strains implicated in neonatal diarrhea, and 100 porcine commensal E. coli. Targets prevalent among PWD isolates but not neonatal diarrhea or commensal collections will have the greatest potential for future vaccines against PWD in pigs. This research will pave the way towards future studies assessing the efficacy of these identified targets as components of a multiple subunit vaccine.
Project Title: Do mast cell stabilizers prevent hyperalgesia?
PI (faculty) contact: Dr. Alice A. Larson
Department: Veterinary Biomedical Sciences
Room number: 235F AnSciVetMed Bldg
Phone number: 4-3650
E-mail: larso011@umn.edu
List names of co-PI’s with affiliation:
Description: In the periphery, there is cross-talk between nerves and the adjacent mast cells. Nociceptors release compounds that activate mast cells, and mast cells, in turn, degranulate and release substances that further sensitize nociceptors, causing hyperalgesia. Large populations of mast cells are also located in dorsal root ganglia (DRG) and the thalamus. If they influence neuronal activity, this would sensitize not only the neurons within one dermatome, but larger populations, resulting in hyperalgesia over larger areas of the body.
In the proposed studies we will examine the effect of nociceptive input on mast cells in DRG, using a model of hyperalgesia induced by the surgical ligation of the L5 nerve, allowing the afflicted limb to be compared to the contralateral control side. These studies involve surgery, histology and behavioral testing in mice.
We hypothesize thatmast cells in the DRG upregulate nociceptive sensitivity. The proposed studies will histologically determine whether hyperalgesia induced by nerve ligation (surgically done) degranulates mast cells and whether the severity of hyperalgesia corresponds with the number of DRG mast cells or their incidence of degranulation. We will also pharmacologically determine whether the hyperalgesia depends on the degranulation of mast cells by using mast cell stabilizers to influence hyperalgesia.
Project Title: Evaluating Round Bale Feeders for Reduced Hay Waste and Improved Horse Health
PI (faculty) contact: Krishona Martinson
Department: Animal Science
Room number: 155C Haecker Hall
Phone number: 612-625-6776
E-mail: krishona@umn.edu
List names of co-PI’s with affiliation: Julia Wilson, Veterinary Population Medicine
Description: Round bales are commonly fed by horse owners, but can result in excessive hay waste and overfeeding. Obesity is a significant equine health concern. Recently developed round bale feeders claim to dramatically reduce hay waste and slow hay consumption. The objective of this research is to evaluate three different types of round bale feeders and their effect on hay waste, horse health, and economics. Research will occur at a private farm with the owners’ consent. Each feeder will be placed in a paddock containing approximately five horses of similar weight. On a daily basis, waste from around each feeder will be collected and weighed. The number of days between each round bale will also be recorded. Collection and weighing of waste hay, and days between bales will be recorded for 30 days or through feeding five round bales. Each horse in the study will be weighed and its body condition score determined at the initiation and conclusion of the study. Other variables such as amount of exercise and concentrate feeding will also be recorded for each horse. The data from this research will help determine ways horse owners can economically feed round bales, reduce hay waste, and improve horse health.
Project Title: Breed-dependent sensitization of canine hemangiosarcoma cells by targeted VEGF receptor blockade
PI (faculty) contact: Jaime Modiano
Department: Veterinary Clinical Sciences
Room number: VMC 410 or 560F Masonic Cancer Research Building
Phone number: 5-7436
E-mail: modiano@umn.edu
List names of co-PI’s with affiliation: Sharkey
Description: We found that breed determines the expression of Vascular Endothelial Growth Factor Receptors (VEGFR) in canine hemangiosarcoma. Specifically, tumors from Golden Retrievers express VEGFR1 at the expense of VEGFR2, while tumors from other breeds (non-Golden Retrievers) express the canonical VEGFR2. In addition, while hemangiosarcoma cells (from all breeds) appear to be insensitive to targeted inhibitors of VEGFR2 in vitro, small molecule inhibitors of VEGFR1 enhance growth of hemangiosarcoma cells derived from Golden Retriever tumors, suggesting this receptor is not only functional, but also acts as a negative growth regulator. For this project, the summer scholar will examine the hypothesis that inhibition of VEGFR1 negative regulation will sensitize Golden Retriever hemangiosarcoma cells to chemotherapeutic agents. Moreover, the scholar will explore if blocking VEGFR1 negative regulation will uncover oncogenic pathways essential for hemangiosarcoma growth and survival.
Project Title: A survey of dairy and swine farms capturing methane
PI (faculty) contact: Bob Morrison
Department: VPM
Room number: 385b; Animal Science / Veterinary Medicine
Phone number: 5-9276
E-mail: BobM@UMN.Edu
List names of co-PI’s with affiliation:
Larry Jacobson; Ag Engineering
Bill Lazarus; Ag Econ
Description: With interest in reducing the accumulation of green house gases and thereby mitigating the impact of climate change, an increasing number of dairy and swine farms are capturing methane from manure. They may be flaring the gas or using it to generate electricity. And some are even earning carbon credits for their efforts. This project will be a survey of farms that are involved in this effort to learn current activities and challenges that they are experiencing.
Project Title: A survey of dairy and swine farms capturing methane
PI (faculty) contact: Bob Morrison
Department: VPM
Room number: 385b; Animal Science / Veterinary Medicine
Phone number: 5-9276
E-mail: BobM@UMN.Edu
List names of co-PI’s with affiliation:
Larry Jacobson; Ag Engineering
Bill Lazarus; Ag Econ
Description: With interest in reducing the accumulation of green house gases and thereby mitigating the impact of climate change, an increasing number of dairy and swine farms are capturing methane from manure. They may be flaring the gas or using it to generate electricity. And some are even earning carbon credits for their efforts. This project will be a survey of farms that are involved in this effort to learn current activities and challenges that they are experiencing.
Project Title: Assessing the biosecurity risk of sow herds located within a regional PRRS elimination project area
PI (faculty) contact: Bob Morrison
Department: VPM
Room number: 385b; Animal Science / Veterinary Medicine
Phone number: 5-9276
E-mail: BobM@UMN.Edu
List names of co-PI’s with affiliation:
Peter Davies; VPM
Scott Dee; VPM
Description: A regional PRRS elimination project has been in operation in Stevens County, MN since 2004. Substantial progress has been made and the project is being expanded to the surrounding 6 counties. A biosecurity risk assessment survey tool has been developed and needs to be conducted at all sow herds within the region. This position will involve being part of the regional effort, being trained on the risk assessment and conducting the survey at all sow herds within the region.
Project Title: Effect of wean age and weight on performance of weaned pigs
PI (faculty) contact: Bob Morrison
Department: VPM
Room number: 385b; Animal Science / Veterinary Medicine
Phone number: 5-9276
E-mail: BobM@UMN.Edu
Description: Some sow herds experience difficulty in getting weaned pigs to start their growth effectively. There are too many “fall-outs” that are often attributed to behavioral maladaption. In this study, we will follow groups of weaned pigs and determine if age or weight at weaning is associated with post weaning “fall out”.
Project Title: Presence of Leptospira in the farm environment
PI (faculty) contact: Claudia Munoz-Zanzi
Department: Veterinary Population Medicine
Room number:
Phone number: 612-626-2849
E-mail: munozzan@umn.edu
List names of co-PI’s with affiliation: Randall Singer, Veterinary and Biomedical Sciences
Description: Leptospirosis is a zoonotic disease that can be transmitted directly or indirectly from animals to humans. It is a known problem for human and animal health in the tropics but it has been understudied in non-tropical areas. The long-term goal is to improve our understanding of the dynamics of transmission of leptospirosis in the U.S. and Latin America and to estimate the impact of human and animal infection. The specific objective of this study is to evaluate the environmental risk of exposure from surface water in farms from Minnesota. Methods include collection and testing of surface water in cattle and swine farms from Minnesota for the presence of bacteria. Completion of this study will provide identification of high risk areas.
Project Title: Evaluation of diagnostic tests for Leptospira infection in humans
PI (faculty) contact: Claudia Munoz-Zanzi
Department: Veterinary Population Medicine/Division of Epidemiology-School of Public Health
Room number:
Phone number: 612-626-2849
E-mail: munozzan@umn.edu
List names of co-PI’s with affiliation: Randall Singer, Veterinary and Biomedical Sciences, Sagar Goyal – Veterinary Population Medicine/Veterinary Diagnostic Laboratory
Description: Leptospirosis is a zoonotic disease that can be transmitted directly or indirectly from animals to humans. It is a known problem for human and animal health in the tropics but it has been understudied in non-tropical areas. The long-term goal is to improve our understanding of the dynamics of transmission of leptospirosis in the U.S. and Latin America and to estimate the impact of human and animal infection. The specific objectives of this study are to compare the performance of several diagnostic tests for detection of Leptospira antibodies in humans and to assess the possibility of false negative results by MAT testing in animal samples. Methods include laboratory testing of human serum samples from Chile and Wisconsin with 3 serologic tests and quantitative evaluation of sensitivity and specificity. A representative number of animal serum samples from the veterinary diagnostic laboratory that tested negative in a MAT panel will be tested with a genus-specific test to quantify the occurrence of infection by serovars that may not be included in the currently used MAT panel. At the completion of the study, we will obtain estimates of prevalence of infection in non-tropical areas and improved parameters of diagnostic accuracy of various tests.
Project Title: Methylation of arsenic in ruminants.
PI (faculty) contact: Mike Murphy
Department: VPM
Room number: E 328
Phone number: 5-1936
E-mail: murph005@umn.edu
List names of co-PI’s with affiliation:
Description: Inorganic arsenic is reported to be a carcinogen – however organic arsenic is not. Arsenic occurs naturally in water and feed products, and arsenic is used as a feed additive. Of particular importance to food is whether arsenic is methylated or demethylated in ruminants. Methylated arsenic is organic and consequently not a carcinogen concern.
Project Title: Novel antidotes for cyanide poisoning.
PI (faculty) contact: Mike Murphy
Department: VPM
Room number: E 328
Phone number: 5-1936
E-mail: murph005@umn.edu
List names of co-PI’s with affiliation: Steve Patterson, Center for Drug Design.
Description: We have recently received funding from NIH to further develop two novel antidotes for cyanide poisoning in the pig model. Efficacy for one of the antidotes has been shown in mice. The efficacy of the antidotes, the dose, and duration, need to be established in a large animal because these aspects cannot be determined in humans for ethical reasons.
Humans and animals may be exposed to cyanide in terrorist attacks, which is the basis for the funding. However, humans and animals are often exposed to cyanide in burning buildings when plastics are part of the fire.
The project allows exposure to one step in the drug development process, arterial catheterization of pigs, determining blood gasses, pH, lactate, and necropsy. A substantial amount of data analysis will occur on the project.
Project Title: Detection of melamine in milk.
PI (faculty) contact: Mike Murphy
Department: VPM
Room number: E 328
Phone number: 5-1936
E-mail: murph005@umn.edu
List names of co-PI’s with affiliation:
Description: Both the pet food recall and infant formula adulteration events in the last 2 years involved adulteration with melamine. The infant formula instance has brought particular attention to the potential for melamine in animal feed to pass through to the milk of cattle eating that feed. The World Health Organization has set an acceptable milk concentration of 1 ppm. However, rapid and cheap analytical methods are needed to determine whether milk does or does not have melamine in it at a concentration of 1 ppm. The goal of this study is to determine which methodologies have the best promise of achieving this goal.
Project Title: Methylation of melamine in ruminants.
PI (faculty) contact: Mike Murphy
Department: VPM
Room number: E 328
Phone number: 5-1936
E-mail: murph005@umn.edu
List names of co-PI’s with affiliation:
Description: Both the pet food recall and infant formula adulteration events in the last 2 years involved adulteration with melamine. The infant formula instance has brought particular attention to the potential for melamine in animal feed to pass through to the milk of cattle eating that feed. The World Health Organization and the Food and Agriculture Organization have set a priority to examine the carryover of melamine from feed to food of animal origin. Questions have also bee raised as to whether melamine can be metabolized into cyanurinc acid by ruminants. The first step in this investigation is to determine whether melamine is metabolized to any appreciable degree in the rumen or the ruminant.
Project Title: Urinary biomarker discovery for canine oxalate urolithiasis
PI (faculty) contact: Michael Murtaugh
Department: Veterinary and Biomedical Sciences
Room number: 239B Veterinary Sciences Building
Phone number: 5-6735
E-mail: murta001@umn.edu
List names of co-PI’s with affiliation: Jody Lulich, Professor of Nephrology, Department of Veterinary Clinical Sciences; Josephine Gnanandarajah, Morris Animal Foundation Fellow, Department of Veterinary and Biomedical Sciences.
Description: Urinary stones, or uroliths, are mineralized concretions formed by the precipitation of poorly soluble organic or inorganic salts in the urinary tract. The incidence of uroliths in dogs has increased greatly in the last 20 years, but our understanding of the underlying causes and conditions that facilitate their formation remains incomplete. Oxalate stones are the most common urolith in dogs. Risk factors of genetic predisposition, infection, endocrinopathies, age, and environment have been implicated in urolithiasis, but diagnostic or prognostic indicators that would aid treatment and prevention are still needed. Here we propose to characterize the proteomic and metabolic constituents of oxalate uroliths to address the hypothesis that accessory proteins and metabolites are associated with stone formation and might serve as diagnostic predictors of disease. Urine from normal and affected dogs and dissolved stones will be analyzed by high performance liquid chromatography (HPLC) and mass spectrometry for profiles that are predictive of health and disease. The student will interact with a clinical scientist, a biochemical scientist and a graduate fellow with advanced technical expertise on a project partially supported by the Morris Animal Foundation.
Project Title: Urinary metabolite biomarkers for canine urate uroliths
PI (faculty) contact: Michael Murtaugh
Department: Veterinary and Biomedical Sciences
Room number: 239B Veterinary Sciences Building
Phone number: 5-6735
E-mail: murta001@umn.edu
List names of co-PI’s with affiliation: Jody Lulich, Professor of Nephrology, Department of Veterinary Clinical Sciences; Josephine Gnanandarajah, Morris Animal Foundation Fellow, Department of Veterinary and Biomedical Sciences.
Description: Urinary stones, or uroliths, are mineralized concretions formed by the precipitation of poorly soluble organic or inorganic salts in the urinary tract. The incidence of uroliths in dogs has increased greatly in the last 20 years, but our understanding of the underlying causes and conditions that facilitate their formation remains incomplete. Risk factors of genetic predisposition, infection, endocrinopathies, age, and environment have been implicated in urolithiasis, but diagnostic or prognostic indicators that would aid treatment and prevention are still needed. Here we propose to characterize the proteomic and metabolic constituents of urate uroliths, derived from purine metabolism, to address the hypothesis that accessory proteins and metabolites are associated with stone formation and might serve as diagnostic predictors of disease. Urine from normal and affected dogs and dissolved stones will be analyzed by high performance liquid chromatography (HPLC) and mass spectrometry for profiles that are predictive of health and disease. The student will interact with a clinical scientist, a biochemical scientist and a graduate fellow with advanced technical expertise on a project partially supported by the Morris Animal Foundation.
Project Title: Biomolecular profiling for assessment of feline purine uroliths.
PI (faculty) contact: Michael Murtaugh
Department: Veterinary and Biomedical Sciences
Room number: 239B Veterinary Sciences Building
Phone number: 5-6735
E-mail: murta001@umn.edu
List names of co-PI’s with affiliation: Jody Lulich, Professor of Nephrology, Department of Veterinary Clinical Sciences; Josephine Gnanandarajah, Morris Animal Foundation Fellow, Department of Veterinary and Biomedical Sciences.
Description: Urinary stones, or uroliths, are mineralized concretions formed by the precipitation of poorly soluble organic or inorganic salts in the urinary tract. The incidence of uroliths in cats has increased greatly in the last 20 years, but our understanding of the underlying causes and conditions that facilitate their formation remains incomplete. Risk factors of genetic predisposition, infection, endocrinopathies, age, and environment have been implicated in urolithiasis, but diagnostic or prognostic indicators that would aid treatment and prevention are still needed. Here we propose to characterize the proteomic and metabolic constituents of urate uroliths, derived from purine metabolism, to address the hypothesis that accessory proteins and metabolites are associated with stone formation and might serve as diagnostic predictors of disease. Urine from normal and affected cats and dissolved stones will be analyzed by high performance liquid chromatography (HPLC) and mass spectrometry for profiles that are predictive of health and disease. The student will interact with a clinical scientist, a biochemical scientist and a graduate fellow with advanced technical expertise on a project partially supported by the Morris Animal Foundation.
Project Title: Serological and oral fluid biomarkers of PRRS disease
PI (faculty) contact: Michael Murtaugh
Department: Veterinary and Biomedical Sciences
Room number: 239B Veterinary Sciences Building
Phone number: 5-6735
E-mail: murta001@umn.edu
List names of co-PI’s with affiliation: Scott Dee, Professor of Swine Medicine, Department of Veterinary Population Medicine; Jeffery Zimmerman, Professor of Preventive Swine Medicine, Iowa State University; and Josephine Gnanandarajah, Morris Animal Foundation Fellow, Department of Veterinary and Biomedical Sciences.
Description: Porcine reproductive and respiratory syndrome is a terrible disease of swine. Discovered less than 20 years ago, The causative virus has evolved from an agent of abortion in sows and mild pneumonia in growing pigs to recent strains that cause mortality of 10 to 50 percent in naïve herds of young, growing, or adult swine. Little is known about the pathogenic mechanisms that have resulted in the dramatically increased virulence. Here we propose to characterize the proteomic constituents of swine serum and oral fluids to address the hypothesis that specific disease signatures resulting from release of signaling molecules, cell membrane proteolysis, and tissue damage will distinguish healthy pigs from those with mild or virulent PRRS. Proteins unique to virulent PRRS will provide insights into host responses associated with health and extreme disease. The student will be able to participate in animal disease research, become familiar with advanced laboratory technologies, gain expertise in noninvasive diagnostic testing, and interact with graduate students, postdoctoral fellows, and staff scientists.
Project Title: Metabolic urinary signatures of struvite uroliths in feline and canine companions
PI (faculty) contact: Michael Murtaugh
Department: Veterinary and Biomedical Sciences
Room number: 239B Veterinary Sciences Building
Phone number: 5-6735
E-mail: murta001@umn.edu
List names of co-PI’s with affiliation: Jody Lulich, Professor of Nephrology, Department of Veterinary Clinical Sciences; Josephine Gnanandarajah, Morris Animal Foundation Fellow, Department of Veterinary and Biomedical Sciences.
Description: Urinary stones, or uroliths, are mineralized concretions formed by the precipitation of poorly soluble organic or inorganic salts in the urinary tract. The incidence of uroliths has increased greatly in the last 20 years, but our understanding of the underlying causes and conditions that facilitate their formation remains incomplete. Struvite, or ammonium magnesium phosphate, is one of the common stone types in cats and dogs. Risk factors of genetic predisposition, infection, endocrinopathies, age, and environment have been implicated in struvite urolithiasis, but diagnostic or prognostic indicators that would aid treatment and prevention are still needed. Here we propose to characterize the proteomic and metabolic constituents of struvite uroliths to address the hypothesis that accessory proteins and metabolites are associated with stone formation and might serve as diagnostic predictors of disease. Urine from normal and affected cats and dissolved stones will be analyzed by high performance liquid chromatography (HPLC) and mass spectrometry for profiles that are predictive of health and disease. The student will interact with a clinical scientist, a biochemical scientist and a graduate fellow with advanced technical expertise on a project partially supported by the Morris Animal Foundation.
Project Title:
Clinical Characterization, Transmission and Comparative Pathology of Selected Low Pathogenicity Avian Influenza (LPAI) Viruses in Poultry
PI (faculty) contact: Rob Porter, DVM, PhD
Department: Veterinary Population Medicine and Veterinary Diagnostic Laboratory
Room number: 232 VDL
Phone number: 612-624-7400
E-mail: porte349@umn.edu
List names of co-PI’s with affiliation:
Marie R. Gramer, Department of Veterinary Population Medicine
Sagar M. Goyal, Veterinary Population Medicine
Description: Low pathogenicity avian influenza (LPAI) infections in poultry vary clinically depending on virus virulence, infection route, management, diet, stressors, and secondary bacterial infections, as well as host species and age. The ability of an AI virus to produce disease, as well as the susceptibility of the host to the virus, varies between avian species. The pathogenicity of Minnesota LPAI viruses for commercial poultry is incompletely defined. In proposed studies, viruses of turkey or wild waterfowl origin will be inoculated into turkeys, chickens, duckling, pheasants and quail, and compared by embryo infectious dose 50, clinical signs and gross lesions elicited in a particular species, histopathological lesions, tissue distribution of virus (PCR, immunohistochemistry), virus shedding, and transmissibility of virus to noninfected birds. Particular attention will be paid to reassortant LPAI viruses, possessing genomic segments derived from swine influenza virus, that were isolated from Minnesota turkeys with respiratory disease Viruses possessing similar hemagglutinin and neuraminidase subtypes, but differing in species from which the virus was originally isolated (turkey or waterfowl) will be compared. This study will provide novel information on the risks that LPAI pose to domestic poultry and will establish a battery of LPAI viruses with well defined biological activity and pathogenicity.
Project Title: Molecular pathogenesis of zoonotic Cryptosporidium parvum
PI (faculty) contact: Mark Rutherford
Department: VBS
Room number: 295e AS/VM office; 74 AS/VM lab
Phone number: 5-4281
E-mail: ruthe003@umn.edu
List names of co-PI’s with affiliation: Shin Enomoto, VBS
Description: Cryptosporidium parvum is a zoonotic parasite of considerable cost to the dairy industry. It causes an acute and profuse diarrhea that impacts growth of the affected calf. C. parvum also infects humans and is associated with large outbreaks usually associated with water contamination. It is a significant concern for immunocompromised individuals. The pathogen attaches to the apical side of the intestinal mucosal epithelial cells, forming a parasitophorous vacuole, but does not invade deeper layers of the intestinal mucosa. This suggests that the interactions between epithelial cells lining the gastrointestinal tractand C. parvum are extremely important for both C. parvum’s ability to successfully complete its life cycle and for the host response to infection. Our work has shown that the parasite can interrupt the molecular pathways leading to apoptosis of infected host intestinal epithelial cells. This project will clone a C. parvum BH3-domain protein thought to be involved in intracellular signal transduction, and express it in human HCT-8 epithelial cells to determine its ability to regulate cell death during infection by C. parvum oocysts. The student will learn expression cloning, cell culture, transfection, and immunofluorescence microscopy.
Project Title: Simulation modeling of foodborne pathogen transmission, sampling strategies, and antimicrobial resistance (multiple projects)
PI (faculty) contact: Randall Singer
Department: Veterinary and Biomedical Sciences
Room number: 300A VSB
Phone number: 612-625-6271
E-mail: singe024@umn.edu
List names of co-PI’s with affiliation:
Description: In this project, you will learn to develop simulation models using programs such as Microsoft Excel. 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. In another project, the student can evaluate whether the number of bacteria analyzed per sample reflects the genetic diversity present in the sample. Finally, in another type of project, the student can develop simulation models predicting the spread of antimicrobial resistance on the farm.
Project Title: Genomic surrogate markers of prion disease
PI (faculty) contact: Pam Skinner
Department: VBS
Room number: 311
Phone number: 612 624 2644
E-mail: skinn002@umn.edu
List names of co-PI’s with affiliation:
Description: Transmissible spongiform encephalopathies, also known as prion diseases, are late onset, progressive, fatal neurodegenerative diseases that affect humans and animals. There is a need to understand prion disease pathogenesis and to develop diagnostic assays to diagnose prion disease prior to the onset of clinical symptoms. We identified alterations in gene expression that occur in the brain and spleen of prion disease-infected mice prior to the onset of clinical symptoms. To further investigate these genes, we have several studies underway. We are currently doing studies using quantitative real-time-RT-PCR, immunohistochemistry, and bioinformatics to 1) determine whether gene alterations also occur in the blood during prion disease, 2) determine whether gene alterations are specific to prion disease or also occur in other related diseases, and 3) determine the cell types in which gene alterations are occurring. The prion disease associated alterations in gene expression identified in our studies are informative to prion disease pathogenesis and may be useful as surrogate markers of disease to diagnose prion disease before the onset of clinical symptoms.
Project Title: A non-terminal equine model of joint injury
PI (faculty) contact: Dr. Troy Trumble
Department: Veterinary Population Medicine
Room number: 225 VMC
Phone number: 4-2676
E-mail: trumb016@umn.edu
List names of co-PI’s with affiliation:
Dr. Mary Boyce, DVM, PhD candidate, University of Minnesota
Dr. Murray Brown, DVM, MS, University of Florida
Description: Soundness problems have a large financial impact on the equine industry, with joint diseases such as osteoarthritis, being a common cause of lameness. Finding better ways to diagnose and treat joint disease is critical to reducing this impact. Osteoarthritis is difficult to diagnose in its early stages when progression of the disease could potentially be reversed. New laboratory tests called “biomarkers” can measure early changes that are specific for joint tissues and can be measured in the blood, joint fluid, and urine. The proposed research is designed to measure biomarkers in a new non-terminal equine osteoarthritis model. Chip fractures will be created in the ankle joints of 16 horses (3- to 6-year old) so that the chips will be similar to what occurs naturally. All horses will be treadmill exercised over a period of 14 weeks. Lameness (including force plate and computer evaluation), blood, joint fluid, and urine will be analyzed at 2 week intervals throughout the study. All chips will be removed at 14 weeks and horses will be adopted out for riding. This work is expected to validate the use of biomarkers to identify early osteoarthritic changes in this model.
Project Title: Adrenal inhibin in dairy cows
PI (faculty) contact: Professor Jon Wheaton
Department: Animal Science
Room number: 495C, AnSci/Vet Med Building
Phone number: 612-624-1225
E-mail: wheat001@umn.edu
List names of co-PI’s with affiliation: Dr. Ricardo Chebel, Theriogenology, University of Minnesota (expected to start in spring, 2009)
Description: The goal of the project is to determine whether the bovine adrenal gland secretes significant amounts of the hormone inhibin. The adrenal gland produces inhibin and evidence indicates it may secrete inhibin into the systemic circulation. Inhibin has an inhibitory effect on the secretion of follicle-stimulating hormone (FSH) from the pituitary gland. The study would be conducted using early post-partum lactating dairy cows. The experimental hypothesis is that adrenal inhibin contributes to post-partum anestrus by inhibiting FSH secretion. The study will examine inhibin concentrations in relation to other ovarian (estradiol and progesterone), adrenal (cortisol and androgens) and pituitary hormones (LH and FSH), ovarian follicular development (transrectal ultrasonography) and production traits (milk production, rate of gain, body condition and fertility). Inhibin also will be assayed in stored plasma from ovariectomzed cows. Cow-side procedures will be conducted in collaboration with the herd's attending reproductive specialist. It is anticipated that this person will be a recent hire, Dr. Richardo Chebel. On- and off-campus dairy herds may be utilized. Laboratory procedures include protein and steroid hormone radioimmunoassays, ELISA, and the immunoaffinity purification, concentration and immunoblotting of inhibin. The student would help design the experiment, conduct laboratory and animal procedures, analyze data and report findings.
Project Title: Analyzing candidate genes for association to cranial cruciate ligament rupture in the Newfoundland dog.
PI (faculty) contact: Dr. Vicki Wilke
Department: Veterinary Clinical Sciences
Room number: 403 VMC
Phone number: 612-625-4966
E-mail: wilke175@umn.edu
List names of co-PI’s with affiliation:
Dr. Mike Conzemius, Veterinary Clinical Sciences
Description: Cranial cruciate ligament rupture (CCLR) represents nearly 20% of dogs that present to university hospitals for hind limb lameness. We have been studying the genetic basis of CCLR in the Newfoundland dog and have identified a 2 million base pair region to be associated with the trait based on SNP chip analysis. We are in the process of fine mapping this region but all the preliminary data has been obtained in the Newfoundland dog. The goals of this proposal are to determine if the genetic markers we found to be associated with the trait in the Newfoundland dog are also significant in related breeds of dogs. The student will gain experience with molecular genetic techniques and association analyses.
Project Title: Prospective evaluation of the effect of weight loss and rehabilitation on adipokine levels and force plate data on overweight dogs diagnosed with unilateral cranial cruciate ligament rupture.
PI (faculty) contact: Vicki Wilke
Department: Veterinary Clinical Sciences
Room number: 403 VMC
Phone number: 612-625-4966
E-mail: wilke175@umn.edu
List names of co-PI’s with affiliation:
Mike Conzemius, Veterinary Clinical Sciences
Description: Adipokines, such as leptin, adiponectin, and resistin, are inflammatory mediators of fat. They are traditionally associated with diabetes and metabolic syndrome but more recently have been noted to perpetuate the clinical signs of arthritis. We have a funded clinical trial evaluating outcome of surgical vs. nonsurgical management of weight loss and rehabilitation on dogs diagnosed with unilateral cranial cruciate ligament rupture. We plan to prospectively monitor their adipokine levels to determine if there is a relationship between adipokines and functional outcome (lameness). The student will be involved in the clinical trial, including obtaining force plate data, DEXA scans, and radiographs of the participating dogs as well as performing adipokine assays and data analysis.
Project Title:Validating HPLC determination of purine metabolites in urine and serum of cats and dogs.
PI (faculty) contact: Dr. Jody Lulich
Department:Veterinary Clinical Sciences
Room number:C346
Phone number:612-625-7277
E-mail:lulic001@umn.edu
List names of co-PI’s with affiliation: Dr. Carl Osborne, Mike Murtaugh, Josephine Gnanandarajah
Description: Measuring the concentrations of purine metabolites (xanthine, allopurinol, uric acid, allantoin) in urine and serum assists in the diagnosis of defects in purine degradation. We have developed an HPLC (high liquid pressure chromatography) method to analyze these analytes in urine. This research is designed to develop a valid technique to measure the same analytes in serum and to investigate optimal sample handling and storage conditions. Ultimately, these techniques will be used to investigate the underlying cause of urate urolith formation in cats.
Project Title:Epidemiology of calfhood diseases: risk factors for calf morbidity and mortality
PI (faculty) contact: John Fetrow
Department:Veterinary Population Medicine
Room number:A311
Phone number:612-625-3776
E-mail:fetro001@umn.edu
List names of co-PI’s with affiliation: Sandra Godden, VPM
Description: The project will take advantage of the College’s affiliation with the newly constructed New Sweden Dairy and will initiate an on-going epidemiologic surveillance and study system on the dairy. By this summer, the dairy will be in full operation, calving roughly 500 cows and heifers per month. Heifer calves born in the facility will be retained on site until weaned at approximately 2 months of age. We will have full access to records of each cow that calves, calf stillbirths, calf morbidity (timing and type of disease) and mortality in the pre-weaned phase. For the project, the student will live in the student dormitory on site. They will be responsible for assembling the data for each calving and heifer calf, including lactation number of the dam, previous lactation reproductive performance, days dry, days carried calf, and difficulty of delivery. Calves will be weighed at birth. Blood samples will be taken from calves at birth and after 24 hours to assess passive transfer of immunity and for storage for possible testing of pre-colostral immune status. The student will be mentored in statistical analysis techniques for risk factors for stillbirth, morbidity and mortality under the operating conditions of a modern dairy operation.
Project Title: A Genome-Wide Screen for Global Regulators of Plasmid-Mediated Virulence
PI (faculty) contact: Timothy Johnson
Department:Veterinary and Biomedical Sciences
Room number: 301B
Phone number:626-2542
E-mail:joh04207@umn.edu
Description: Plasmids are key agents of change in bacterial populations. In a single conjugative transfer event, these extrachromosomal elements have the ability to provide a recipient bacterium with ability to cause disease, ability to resist multiple antimicrobial agents, and/or ability to survive in unusual environments. Despite its importance, the complex interactions between a plasmid and its host chromosome are poorly understood. This project will focus on the identification of chromosomal genes regulating plasmid-encoded virulence factors. The Summer Scholar’s student will perform a genome-wide screen for regulatory elements using a variety of molecular techniques, including gene fusions, transposon mutagenesis, DNA sequencing, and expression microarrays. This project will thus employ ‘cutting-edge’ approaches towards understanding plasmid regulation.
Project Title: Utilizing Reverse Vaccinology to Identify Vaccine Candidates Against Escherichia coli Causing Post-Weaning Diarrhea in Pigs
PI (faculty) contact: Timothy Johnson
Department:Veterinary and Biomedical Sciences
Room number: 301B
Phone number:626-2542
E-mail:joh04207@umn.edu
List names of co-PI’s with affiliation: Richard Isaacson, UMN, VBS
Description: Post-weaning diarrhea (PWD) causes significant morbidity and mortality towards pigs, and therefore results in significant annual losses to the swine industry. The overall goal of this project is to identify suitable vaccine candidates that might be used to prevent porcine post-weaning diarrhea. To do so, a global “reverse vaccinology” approach is being used. To enable this approach, we have completed the first genome sequence of an enterotoxigenic Escherichia coli strain implicated in porcine PWD. A computational “reverse vaccinology” approach has been employed in an effort to identify and characterize suitable vaccine candidates from our genomic sequence. Our computational approach has identified 50 genes representing the most suitable vaccine candidates, based upon their predicted protein characteristics. This Summer Scholars project will assess the prevalence of these genes among porcine E. coli strains implicated in PWD, porcine E. coli strains implicated in neonatal diarrhea, and porcine commensal E. coli. Targets prevalent among PWD isolates but not neonatal diarrhea or commensal collections will have the greatest potential for future vaccines against PWD in pigs. This research will pave the way towards future studies assessing the efficacy of these identified targets as components of a multiple subunit vaccine. The Summer Scholar’s student will gain experience in molecular biology and microbiology techniques, bacterial genome analysis, plasmid biology, and tissue culture.
Project Title:Maternal Influences on Neonatal Immune Response
PI (faculty) contact: Tom Molitor
Department:Veterinary Population Medicine
Room number:225 VMC office.
Phone number:612-625-5295
E-mail:molit001@umn.edu
List names of co-PI’s with affiliation:
Sam Baidoo –Animal Science
Simone Oliveira-VPM
Meggan Bandrick DVM/PhD grad student--VPM
Description: Transfer of immunity from sow to neonate is an important means of providing immediate immunity to various pathogens in piglets. In fact, since piglets are born without any specific immunity, maternal immunity in the form of colostrum is critical for piglets to survive antigen challenge within the first few weeks of life. While the role of transferred maternal antibody in the piglet is quite clear, the role of passively transferred cells remains to be elucidated. The proposed studies aim to determine if passively transferred maternal immunity, specifically colostral lymphocytes, affects immune development in piglets. Piglets with known immune statuses to Mycoplasma hyopneumoniae, as determined by maternal vaccination and cross fostering, will be vaccinated and later challenged with M. hyopneumoniae. The impact of transferred maternal colostral immunity on the piglet’s response to vaccination and challenge will be evaluated. This project involves working both with pigs and in the laboratory. Activities working with animals include handling pigs as well as collecting blood and colostrum.. Laboratory work includes performing a battery of immune assays on the blood and colostrum.
Project Title:Immune function in Pteropus bats: Improving bio-monitoring capacity in a major wildlife reservoir for emerging infectious disease.
PI (faculty) contact: Katey Pelican
Department:Department of Veterinary Population Medicine
Room number: 136 B Andrew Boss Laboratory
Phone number: 612-625-8561
E-mail:pelicank@umn.edu
List names of co-PI’s with affiliation: Jon Epstein, DVM, MPH, Consortium for Conservation Medicine (CCM), New York, NY; Peter Daszak, Ph.D. CCM, New York, NY Allyson Walsh, PhD, Lubee Bat Conservancy, Gainesville, FL.
Description:Bats are an important reservoir for an increasing number of emerging viral zoonotic diseases that cause significant human mortality. Most recently, highly lethal Hendra virus (HeV) and Nipah virus (NiV) representing a new genus of paramyxovirus (Henipavirus) have emerged from Pteropus spp bats in Australia and Southeast Asia respectively. Recent research indicates that physiologic changes in female bats associated with pregnancy and parturition may play a role in viral dynamics and cycling in these bats. We hypothesize that immune changes in late pregnancy and early lactation alter immune function in Pteropus bats, and that these changes result in seasonal outbreaks of henipavirus in bat colonies that spillover into human populations. In order to test this hypothesis, more information is needed about the basic immunology of Pteropus bats. Specific Aim: to validate immune function analytical techniques in Pteropus bats to improve physiologic bio-monitoring capabilities in these important wildlife reservoirs. This study will validate, for the first time, immune monitoring techniques as tools to better understand the physiologic correlates of emerging viral infections in free-ranging bats. Humoral immunity will be examined by measuring the sub-types of immunoglobulin G (IgG) and immunoglobulin M (IgM). Innate or non-specific immunity will be measured by assessing Natural Killer and phagocytic activity in freshly collected leukocytes.
Project Title: Anthelmintic Resistance in Zoo Animals
PI (faculty) contact: Bert Stromberg
Department: Veterinary and Biomedical Sciences
Room number: 204 Vet Sci Building
Phone number: 612-625-7008
E-mail: b-stro@umn.edu
List names of co-PI’s with affiliation: Dr. Mickey Trent, VPM
Description: Anthelmintic resistance, the inability of deworming compounds to remove worms, is becoming more prevalent throughout the United States. The sheep and goat industry has wide spread resistance to many of the compounds available. A national survey is suggesting resistance in many of the cattle parasites. This project will explore the prevalence of resistance to the dewormers in the hoofed stock at the zoos in the Twin Cities. This will use the Fecal Egg Count Reduction Test to determine the efficacy of anthelmintics and attempt to determine an optimal regimen to prevent the development of resistance.
Project Title: Evaluation of the Sensitivity of slaughter surveillance for bovine TB in cattle.
PI (faculty) contact: Scott Wells
Department: CAHFS
Room number: 136D ABLMS
Phone number: 5-8166
E-mail: wells023@umn.edu
List names of co-PI’s with affiliation:Tim Goldsmith, CAHFS
Description: The use of slaughter surveillance for the detection of bovine tuberculosis (TB) in the US cattle herd is an important part of the eradication plan for bovine TB in the US. However the characteristics as far as sensitivity for this practice to detect bovine TB are largely unknown. In other projects we have looked at the test characteristics for other tests such as the caudal fold test, comparative cervical test, and the gamma interferon test. As we move forward with projects evaluating the current state of the diagnostics for bovine TB and the possibility of USDA changing the approach taken with the bovine TB eradication plan, the slaughter surveillance is an important part of this evaluation. We propose that a summer scholar with interest in this area would fill and important role. Initially we would like the summer scholar to perform a literature review and to summarize all known data relevant to the issue of slaughter surveillance for bovine TB. Further work would be to gather information from USDA-APHIS and FSIS personnel in Minnesota to add to the report, and visit MN slaughter establishments to become familiar with the process and surveillance system. The result would be a summary paper on the topic of slaughter surveillance for bovine TB that includes Minnesota specific data that will be valuable for further work with bovine TB.
Project Title: Role of extracellular matrix in post-BMT lung injury
PI (faculty) contact: Angela Panoskaltsis-Mortari
Department: Pediatrics (Blood & Marrow Transplant Program; Pulmonary & Critical Care Medicine)
Room number: office 660A MCRB (CCRB)
Phone number: 6-2950
E-mail: panos001@umn.edu
Description: Hematopoietic stem cell transplant (HSCT)-related lung injury is a frequent complication and we wish to develop preventative and treatment strategies using murine preclinical models. The injury results from a variety of insults to the lung, including toxic effects of HSCT conditioning regimens, immunologic cell-mediated injury, inflammatory cytokines and extracellular matrix interactions. We are studying the roles of matrix metalloproteinases (MMPs) on cellular infiltration and pulmonary function after bone marrow transplant (BMT) using our established mouse model. Please see the following paper for descriptions of the model: Panoskaltsis-Mortari A, Tram K, Price A, Wendt C, Blazar BR. A new murine model for obliterative bronchiolitis post-bone marrow transplant. Amer. J. of Respir. and Crit. Care Med., Epub June 15, 2007; 176:713-723, 2007.
Project Title: Pharmacogenetic implications of anticancer chemotherapeutics
PI (faculty) contact: Jatinder Lamba
Department: Experimental and Clinical Pharmcology
Room number: 14-281, Moos Tower
Phone number: 612-624-8651
E-mail: lamba004@umn.edu
Description: Our lab is focused on studying pharmacogenetics of anticancer drugs. We use HAPMAP lymphoblast cell lines from subject with European and African ancestry to understand interindividual differences in drug sensitivity. The cell lines (~ 90 cell lines) are treated with compounds of interest and the cytotoxicity profile is analyzed with genome wide gene expression and SNP data. We also do deep sequencing of candidate genes within these cell lines in order to identify potential single nucleotide polymorphisms associated with response. In parallel to this we analyze the high priority SNPs and genes with response in patients undergoing treatment with same anticancer agents. Student will get exposure to this bench to bedside research that has basic research linked with translational patient oriented studies. Our long term goal to move pharmacogenetic testing into the clinical setting to improve safety and efficacy of drug therapy. Particularly for this summer we have a project in which an antileukemic compound decitabine will be analyzed in these samples. Students will get exposure to multitude of tissue culture and molecular biology technique. DNA, RNA isolation methods, cell based cytotoxicity assays etc.
Project Title: Molecular characterization of osteosarcomas
PI (faculty) contact: Subbaya Subramanian
Department: Laboratory Medicine and Pathology
Room number: 14-271
Phone number: 612-626-4330
E-mail: subree@umn.edu
List names of co-PI’s with affiliation:Dr Jaime Modiano
Director, Animal Cancer Center, Veterinary Medical Center
Perlman Professor of Oncology and Comparative Medicine, Veterinary Clinical Sciences
Email: modiano@umn.edu
Phone: 612-625-7436
Description: Our laboratory is equipped to carryout microRNA research. We are primarily interested in understanding the biology of sarcomas. Recently, our project “Molecular characterization of osteosarcomas” was funded by the AHC Faculty Research Development Grant award. In this project, we will use comparative genomic approaches to understand the human and dogs osteosarcomas. We have generated sufficient preliminary data on gene and microRNA expression profiles for both human and dog osteosarcomas. As a next step in the project we would like to understand the functional role played by these microRNAs in the tumor onset and progression using in vitro cell culture models. This will be a great opportunity for a summer student to learn the biology of microRNA and also learn technical skills that are used to study microRNA functions.
Project Title: Gene-targeting of miR-210 and miR-424 in mice
PI (faculty) contact: Yan Zeng
Department: Pharmacology
Room number: 2-274 NHH
Phone number: 612-625-4479
E-mail: zengx033@umn.edu
Description: microRNAs (miRNAs) are small RNA molecules that regulate gene expression and many important biological processes. We have found that the expression of two miRNAs, miR-210 and miR-424, increased when human endothelial cells were placed under hypoxia, and that miR-210 and miR-424 functioned partly by regulating the cellular hypoxic responses in vitro. We hypothesize that miR-210 and miR-424 may contribute to angiogenesis and tumorigenesis. To dissect the in vivo functions of the two miRNAs, we will knock out their expression in mice and examine the mouse phenotypes.
Project Title: Thermochemical Ablation in a Pig Model with Imaging Correlation
PI (faculty) contact: Dr. Erik Cressman
Department: Radiology
Room number: Mayo B228F
Phone number: 612-626-5540
E-mail: cress013@umn.edu
Description: We study new ways to ablate solid tumors such as primary liver cancer, but the methods are applicable to any solid tumor. Current treatment such as radiofrequency ablation has limitations we seek to overcome, especially cost and heat sink effects. Injectable chemical ablation methods (ethanol or acetic acid) have received less attention despite a long track record of safety and efficacy due to the number of required treatments (systemic toxicity limits each dose). Thermochemical ablation exploits simple exothermic chemistry in situ using a prototype device we created in order to coagulate tissues with larger treatable volumes yet lower systemic toxicity than seen with ethanol or acetic acid. We use imaging for both guidance during a procedure and after to monitor the effects of a procedure. We are using a pig model in which we expose the liver, create our lesions, isolate the vessels, perfuse the treated organ with contrast and/or dye, and then image the liver after it is explanted. We have two projects in which we will be using 23 more pigs and imaging with CT, 1H MR, MR thermography, and more recently, 19F MR. We also do much work with available ex vivo pig liver and test our methods using thermocouples, pH probes, and infrared (thermal) imaging. Surgical exposure and harvest of pig liver; vascular isolation for perfusion; some aspects of animal model development; exposure to CT and MR imaging techniques and methods of contrast; new investigational ablation techniques; infrared thermal imaging of ablated tissues. Also potential to learn induction and intubation for general anesthesia in pigs.
Project Title: Enhancement of Brain Tumor Vaccine Therapy by Intratumoral Interferon Gene Transfer through Blood Outgrowth Endothelial Cell Carrier Based Delivery System
PI (faculty) contact: Arkadiusz Dudek, MD, PhD, Associate Professor
Department: Medicine, Division of Hematology, Oncology, and Transplantation
Room number: 14-138 Moos Tower
Phone number: 612 624-6610
E-mail: dudek002@umn.edu
List names of co-PI’s with affiliation:John Ohlfest, PhD, Department of Pediatrics
Description: The central limitation to gene therapy of high-grade glioma is the inability to target diffusively infiltrative tumor cells that remain after surgery, often migrating several centimeters away from the bulk tumor. One of the exciting strategies to overcome this conundrum is to use genetically engineered “tumor-seeking” autologous cells to produce a therapeutic protein of interest. Based on paradigm of special attraction to tumor vasculature and its angiogenesis drive, we have used blood outgrowth endothelial cell progenitors (BOEC) for this purpose and demonstrated protracted expression of intratumoral gene of interest in extracranial tumor models. We have also previously determined that adenoviral interferon gamma (IFN-) gene transfer has synergistic efficacy with anti-tumor vaccination in a transplanted GL261 mouse glioma model, and ii) that BOEC engineered to secrete soluble VEGF receptor (sFlt1) prolongs survival of mice in a novel spontaneous glioma model that is more infiltrative than transplanted models. In order to overcome several limitations of adenoviral vector based gene therapy, we herein propose systemic injection of engineered to produce interferon BOEC, which will migrate to vascular niches within gliomas and will produce in tumor location quantities of interferon attractive enough to activate innate and adaptive immune responses leading to augmentation of the vaccine effect. Endothelial progenitor cell culture, gene transduction, fluorescence activated cell sorting
Project Title: Effect of Dietary Chemopreventive Agents on Canine Osteosarcoma cells
PI (faculty) contact: Fekadu Kassie
Department: Veterinary Clinical Sciences
Room number: Masonic Cancer Center 560E
Phone number: 612-625-9637
E-mail: kassi012@umn.edu
List names of co-PI’s with affiliation:Dr. Jaime Modiano
Description: My lab is interested to assess the effect of dietary cancer chemopreventive agents (Epigallocatechin gallate from green tea, indole-3-carbinol from Brassica vegetables, and pomegranate from pomegranate juice extract) on the viability, proliferation and invasion and migration of canine osteosarcoma cells. Once the effect on the aforementioned phenotypes is established, potential mechanisms involved will be examined using flow cytometry, Western blot, and gene expression assays. Promising agents will then be further pursued in mouse models. Techniques or skills the student will learn include cell culture techniques, cell viability and proliferation determination, assessment of cell migration and invasion, Western analysis, the use of flow cytometry, and if time permits, RNA isolation, PCR, quantitative-PCR.
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