The Summer Research Program at Ohio State's College of Veterinary Medicine offers students hands-on experience in research areas ranging from the health and wellness of animals to the safety of food products, to understanding the basic mechanisms of disease. In 2015, 27 students were selected to participate in research; learn more about their individual studies below.
Hearts of infant mice have self-healing abilities, researchers look closer
Did you know that some amphibians and fish have hearts that regenerate muscular tissue cells following injury? This healing mechanism, called cardiac regeneration, is sustained throughout the creatures' lives.
But for humans and other mammals, the heart’s reparative ability is confined to a small window of time during infancy. For mice, studies have shown that this window of time is about seven days. The heart of an infant mouse will self-repair in response to damage during this period, after which the capacity for cardiac regeneration is lost.
Second-year student Sylvie Cohen closely examined cardiac regeneration processes in one-day-old mice this summer at the National Heart, Lung and Blood Institute’s Laboratory of Molecular Biology. Cohen’s focus was on studying the molecular and cellular channels underlying heart-regeneration in mice.
Cohen and her team worked in the lab of Dr. Toren Finkel, senior investigator at the NIH’s Laboratory of Molecular Biology. First, the team wanted to test whether the infant mice’s hearts would actually repair themselves following injury. To do this, a microsurgery was performed on the experimental group that involved cutting off blood supply to the left anterior descending coronary artery, inducing a heart attack (modeled in figure to the right).
After 21 days, the mice that had heart attacks had fully recovered as their hearts had gradually generated new muscular tissue. Cohen and her team were able to see the cardiac regeneration process in action through histologic analyses of the mice’s heart tissue. As seen in the figure below the heart increasingly repaired itself over time, getting back to normal around day 21.
In addition to testing the mammalian heart’s capacity to regenerate for a brief period after birth, Cohen and her team also looked at what they consider a key-regulator in the cardiac regeneration process: a gene called BMI1. BMI1 has been shown to play an important role in cardiac muscle development, so researchers have hypothesized that it’s vital during cardiac regeneration.
To measure BMI1’s effect on heart regeneration, Cohen’s team compared the rate of cardiac healing in normal infant mice against BMI1-knockout infant mice. They found that the mice without the BMI1 gene had a reduced ability to renew cardiac muscle tissue, suggesting that BMI1 “is an important regulator of cardiac regeneration,” Cohen said.
Heart disease is the leading cause of death in the U.S., claiming the lives of more than 600,000 people per year, according to the Centers for Disease Control and Prevention. “Identifying key regulators of the cardiac regeneration process is an important step toward potential regenerative therapies such as gene therapy or pharmaceuticals” Cohen said.
Working with doctors and students from both veterinary and human medicine really enhanced the team’s collaboration and Cohen’s understanding of the research, she said. "It helped us maintain a holistic view."
This study was a part of the NIH’s Summer Internship Program in Biomedical Research for Veterinary Medical Students.
Studying effects of Toxoplasma gondii on mice
An estimated 30 percent of the world is infected with the parasite Toxoplasma gondii, including 60 million people in the U.S., according to the Centers for Disease Control and Prevention.
Second-year student Mary Carter spent her summer at Stanford University studying the molecular underpinning of the parasite and its infectious process in mice.
"T. gondii is a very complex and successful parasite,” Carter said. “We’re still trying to figure out how it infects such a broad range of hosts while simultaneously altering the host’s immune response to avoid detection.”
The parasite causes a condition called Toxoplasmosis, which can cause a range of issues in people who don’t have a fully functioning immune system including fever, pneumonia, chronic inflammation, central nervous system disorders and fatality. Most healthy adults are asymptomatic and completely unaware they are infected.
T. gondii lives and reproduces in cats without affecting them. Most humans and other intermediate hosts (such as mice) are presumed to acquire it through exposure to infected cat feces or poorly cooked food. It can also be transmitted from mother to child during pregnancy, which is why pregnant women are strongly advised to avoid scooping cat litter. There are two stages of T. gondii infection: acute and chronic. If caught in the acute stage, the disease can be treated, but since it’s hard to detect and requires a specific blood test it often moves to the chronic stage, creating cysts in muscle and brain tissue . Recent studies have linked T. gondii with an increased incidence of mental disorders like schizophrenia and bipolar disorder, which is plausible since it affects the brain.
When mice are infected with T. gondii, they show lethargy, severe weight loss and intestinal inflammation during the acute stage, Carter said. After about 14 days they start to recover, but the weight loss and stunted growth (called wasting) remains for the rest of their lives.
Carter and her research team at Stanford (shown on right) want to understand how T. gondii causes weight loss in mice by examining its molecular processes throughout infection. They also measured differences in food intake, body weight, muscle and fat mass. Results are currently pending, and will be useful in understanding the wasting processes that occur in diseases like MS, cancer cachexia or chronic kidney disease.
Carter said she was interested in infectious disease research because her cat died of Feline Infectious Peritonitis when she was young, and there was very little information about why FIP occurred in cats or how it was treated.
“There are still so many diseases, including emerging diseases, that we don’t understand,” she said. “We have a lot of great information on T. gondii, but there is still a lot to learn.”
Toxoplasmosis is considered a “Neglected Parasitic Infection,” one of five parasitic diseases that the CDC has identified for public health action.
Testing quality of produce at local groceries, farmer's markets
Daniela Korec, third-year student, spent her summer testing produce from various farmer’s markets and retail grocery stores in Central Ohio for the presence of antimicrobial resistant bacteria.
Along with Dr. Tom Wittum, professor and interim chair of the Department of Veterinary Preventive Medicine, Korec tested around 200 samples of produce from farmer’s markets and grocery stores for resistant strains of bacteria and coliform, a class of bacteria that comes from the feces of mammals. Coliform levels are commonly used to measure sanitary quality for foods and water.
Throughout the season, Korec bought leafy greens, cucumbers and tomatoes from different locations at the beginning of each week. These samples were placed into Buffered Peptone Water for the detection and measurement of bacteria.
The research team hypothesized that produce from farmer’s markets would have a higher prevelance of resistant bacteria and coliform contamination, Korec said, since they’re more likely to use manuer-derived fertilizer and local surface water.
“Livestock are an important emergence resovoir for zoonotic, food-borne transmission of resistant bacteria,” Wittum said. “The use of antimicrobial drugs in veterinary medicine inevitably results in the dissemination of antimicrobial resistance in a variety of animals.”
Out of the 200 samples, six tested positive for bacteria that is resistant to third-generation antibiotics Cephalosporin and Cefoxitin. Of those, four were from farmer’s markets. This bacteria produces enzymes, called beta-lactamase, that provide resistance to some antibiotics. Beta-lactamase enzymes break the drugs’ structure, rendering it ineffective. No Salmonella was detected in the produce, Wittum said.
The strains of bacteria they found aren’t necessarily harmful, but the study aims to look at the bigger picture of antimicrobial resistance, its future effects, and how these strains of bacteria are getting into the food humans consume.
“Antimicrobial resistance is a hot topic, especially in veterinary medicine” Korec said. “It’s something I would be interested in doing next year as well.”
Health and habitat analysis of endangered Ohio rattlesnakes
This summer, second-year student Katie Backus completed a comprehensive health analysis of massasauga rattlesnakes in partnership with the Ohio Department of Natural Resources. The data will be studied along with land use and habitat condition.
Eastern massasauga rattlesnakes dwell in northeastern regions of the U.S., including Ohio. The species has been a candidate for the Federal Endangered Species Act since 1999, according to the U.S. Fish and Wildlife Service.
The decline of massasauga rattlesnake populations is mostly due to human and agricultural activity as well as habitat loss or destruction. The snakes typically inhabit wetland areas.
The research team tracked and captured massasaugas to acquire blood samples, swab tests for fungal disease and height and weight measurements. They’re also reviewing data on water quality, vegetation density and land use in surrounding areas. Water that flows downstream from farms may contain chemicals associated with agricultural runoff, which has been observed to cause adverse effects in other species.
“Agricultural runoff could be weakening massasaugas’ immune systems,” Backus said, “Possibly predisposing them to fungal diseases and other health issues.”
Backus and her team, led by Greg Lipps, amphibian and reptile conservation coordinator and conservation biologist, were able to capture approximately 55 massasaugas in northeast Ohio. Around 20 were recaptures. The results from fungal disease tests are still processing.
To capture the massasaugas, Backus and her team would walk around in protective gear with snake tongs and bags. Once captured, they would guide the snakes head-first into a plastic tube to prevent biting (as they are venomous), to perform diagnostics. A stress measure - a hormone called leptin - was taken into account during the health assessment.
The results of the study will help the ODNR with conservation efforts, as not much is currently known about the relation between massasauga health and habitat. The ODNR will likely try different techniques on different plots of lands to see what works for the snakes, Backus said.
“I learned so much throughout this process,” she said. “Not only handling snakes, but about government wildlife departments, the history of Ohio’s environment and ecology in general.”
Veterinary medicine plays many roles, and conservation medicine is an important one. This study is an example of how veterinary research can intertwine factors of human, animal and environmental health.
Acute Lung Injury in influenza patients
Patients with severe cases of influenza sometimes develop Acute Lung Injury (ALI), a highly damaging condition that can be fatal. Treatment options are limited.
MicroRNA (miR) are non-coding RNA molecules that take part in the regulation of gene expression, and they’ve been observed to act abnormally in inflammatory diseases, some forms of cancer and more.
Last summer, third-year student Leon Schermerhorn studied the molecular structure of influenza-induced ALI lung cells and, with his team, was able to conclude that a single miR, miR-155, may play a direct role in the progression of the disease. The team, led by associate professor in the Department of Veterinary Biosciences Dr. Ian Davis, discovered this by determining all miR expression levels in ALI lung cells. The results showed that miR-155 was highly overexpressed by alveolar type II (ATII) cells , which are the primary site of influenza virus replication. As influenza increases in severity, miR-155 expression becomes greater. This is harmful because an upregulation of miR-155 seems to provoke a raise in several types of white blood cells and signaling proteins, causing lung inflammation.
Since miR-155 expression by ATII cells could be responsible for the progression of influenza-triggered ALI, Schermerhorn and Davis hypothesize that miR-155 may be a target for therapeutic intervention. Influenza-induced ALI becomes less severe in mice that ATII cell miR-155 expression has been blockaded, called miR-155-knockout mice.
This summer, Schermerhorn is testing a gene therapy method’s ability to delay onset or reduce severity of influenza-induced ALI in mice. The method involves inserting pieces of specially engineered DNA – in this case lipoplexes carrying antagomiRs - into mice that will target ATII cells and inhibit miR-155 expression. His results will give further data on the role of miR-155 in influenza development in general, as well as the efficacy of inhibiting ATII cell miR-155 expression with antagomiRs.
“Research in public health and infectious diseases has always interested me; I like to solve problems,” Schermerhorn said. “Since influenza is a high-consequence pathogen, this study was a good fit from the start.”
Evaluating methods of diagnosing, treating septic newborn foals
The leading cause of death for newborn foals is septicemia (sepsis), which is an inflammatory response to an infection that can lead to potentially fatal complications. Foals are more susceptible to this condition than other animals because the manner in which maternal antibodies are passed from the mare to the foal. Low immunoglobulin levels leave foals vulnerable to infections.
In response to sepsis, foals normally undergo a stress response characterized by the secretion of hormones from the hypothalamus, pituitary gland and adrenal gland. Many of these hormones are steroid hormones, which are vital to organ development, energy regulation, electrolytes, blood pressure and modulating inflammation. A hormone called ACTH (adrenocorticotropic hormone) is responsible for triggering the creation of these hormones in the adrenal gland.
Severely septic foals may develop a problem called relative adrenal insufficiency (RAI) in which the adrenal gland produces insufficient amounts of steroid hormones in response to ACTH.
Second-year student Jillian Minuto is looking at a method that may improve the diagnosis, prognosis and treatment of critically ill foals with RAI.
Because septic foals with RAI have such a poor ACTH response, Minuto and Dr. Ramiro Toribio, associate professor in Veterinary Clinical Sciences, believe that administering a high dosage of ACTH into the blood stream of sick foals may be used as a diagnostic tool and potential treatment to combat complications.
The research team is testing blood samples from hospitalized newborn foals after receiving a high dose of ACTH to assess the function of their adrenal gland, Minuto said. The samples are from foals admitted to the Galbreath Equine Center as well as two equine hospitals in Lexington, Kentucky: Haggard Equine Medical Institute and Rood & Riddle Equine Hospital.
Minuto knew she wanted to be involved in equine internal medicine research even before applying to the Summer Research Program. “I’m gaining a new respect for the scientific process,” she said.
The study is funded by the Morris Animal Foundation.
Understanding how influenza affects cystic fibrosis patients
An estimated 30,000 people in the U.S. are living with Cystic Fibrosis (CF), a fatal genetic disease, according to the Cystic Fibrosis Foundation patient registry.
CF can affect many parts of the body, but it primarily impairs lung function. The lungs in a person with CF are colonized and infected by bacteria from a young age due to poor mucus clearance, which results in chronic inflammation. This makes them susceptible to various infections, and seasonal influenza viruses in particular present a huge risk. When CF patients contract influenza, it can cause severe, sometimes life-threatening symptom exacerbations, making their lungs vulnerable to additional bacteria. Currently, winter CF exacerbations are difficult to treat.
Part of the problem may be an abnormal increase in activity of proteins called pattern-recognition receptors (PRRs) following infection. PRR signaling usually helps the immune system detect viral infection to begin fighting it off, but an excessive response to viruses can cause severe inflammation.
Second-year student Sarah Young is working with Dr. Ian Davis, associate professor in the Department of Veterinary Biosciences, to examine the molecular processes behind influenza infection in CF patients, specifically abnormal PRR signaling in infected lung cells. Young and Davis hypothesize that irregular PRR signaling causes the excessive inflammatory response in CF patients with influenza. To determine if their hypothesis is correct, Young is infecting both regular and CF human airway cells with influenza A virus to examine how PRR signaling differs between groups. The cell cultures that she’s working with use cells from donor lungs, gathered by Dr. Mark Peeples of Nationwide Children’s Hospital.
Once complete the study will provide new information on the natural immune response of CF patients to influenza infection, said Young, who was born with the disease.
“It’s rare to get the chance to research the disease you actually have,” she said. “It has given me more interest and motivation.”
CF is only known to occur in humans, but the study utilizes Young’s knowledge in veterinary medicine nonetheless, Davis said.
“Veterinarians have a great role to play in human medical research,” Davis said. “We have a different perspective, and there are not enough of us involved in it.”
Measuring benefits of environmental enrichments on dairy calves
To prevent the spread of infection and disease, dairy cattle farmers separate calves from each other for approximately six weeks until they are weaned from milk. Though beneficial to health, this practice may hinder calves’ social and cognitive development as well as lead to abnormal habits.
Young calves sometimes display excessive sucking and licking behaviors, often directed toward inappropriate sources such as the enclosure or another calf. As they progress through life, the behaviors can become quite exaggerated and harmful, said Dr. Katy Proudfoot, assistant professor in Veterinary Preventive Medicine and extension specialist in animal welfare and behavior. Letting calves feed naturally rather than from a bucket can help reduce this habit, but many producers are hesitant to adopt the practice.
“Veterinarians were the ones who first came up with the practice of separating dairy calves, as a vital health precaution,” Proudfoot said. “But now we’re recognizing that creating a more complex environment could help calves later in life.”
Second-year students Hannah Manning and Emily Cosentino, who are working under Proudfoot’s direction, are studying the impact of four environmental enrichments on individually housed dairy calves. They hope to see improved social skills and overall welfare in calves who are provided the enrichments, as well as decreased sucking behaviors. They include a slightly larger pen size, a brush to rub up against, an artificial teat and rings to suck on and a tube filled with molasses to stimulate licking behavior.
The team is looking at ten calves in each group – one with environmental enrichments and one without – at Ohio State’s Waterman Dairy Center. They are continually capturing video footage of the calves during their research so they can analyze it from start to end.
“I’ve never had experience with dairy cows,” Manning said. “Working with them this summer has taught me patience and shown me that there’s still a lot more we can figure out.”
The study is mostly preliminary, and will produce data about the relationship between calf housing and animal welfare. If the enrichments prove to be beneficial, the team thinks it would be realistic for dairy cow farmers to start providing similar elements to calves.
Raw pet food is growing in popularity, but is it safe?
Raw pet food has a growing consumer base, said third-year student Paulynne Bellen, but the food may not come without health risks.
One concern is that raw pet food can sometimes carry a bacterium called Listeria monocytogenes, among other foodborne bacteria, since it does not go through the cooking and steaming processes that dry pet food does.
If ingested, L. monocytogenes can cause more extreme symptoms than E. coli, such as infection, fever, gastrointestinal problems and sometimes death. The bacterium can survive in low temperatures and in the presence or absence of oxygen, which is how it likely gets into some raw pet food. L. monocytogenes poses a much higher risk for animals (including humans) that are immunocompromised.
Bellen and Dr. Wittum, research mentor, professor and interim chair of the Department of Veterinary Preventive Medicine, are testing 120 raw pet food samples for the presence of L. monocytogenes, E. coli and Salmonella. They are comparing the levels of foodborne pathogens found in each sample to the four standard processing methods used in raw pet food production: freeze drying, high-pressure pasteurization, raw freezing and dehydration.
This does not mean that all raw food is unsafe for pets to eat or without its benefits, and some veterinarians regularly recommend it, Bellen said.
“As a scientist, you can’t be swayed either way without the facts,” she said. “We just want to determine if one processing method is better at keeping bacteria out than the others, which would allow us to guide pet owners toward the safest kinds of raw food.”
The FDA has issued recalls on several major raw pet food brands and companies in recent years, including three in 2015, brand names Primal, OC Raw Dog and Vital Essentials .
Bellen said that the study has improved her skills in the lab and in responding objectively to a controversial issue. The team expects to see several food samples test positive for foodborne bacteria, Wittum said.
Searching for behavioral clues in horses with hard-to-detect parasite
It's bad when an animal gets sick, and worse when their illness is extremely difficult to diagnose. Equine Protozoal Myeloencephalitis, or EPM, is a neurologic disease that occurs in horses, and can affect their entire central nervous system.
Veterinarians often face a challenge in diagnosing EPM, said third-year veterinary student in the Summer Research Program Lauren Diangelo, who’s currently studying the disease. Identifying EPM is challenging because it’s caused by a tiny parasite that could be living almost anywhere in an infected horse’s central nervous system, which includes the brain and spinal cord, making diagnostics difficult and risky. The parasite originally lives in animals such as opossums or barn cats, and horses usually acquire it through ingesting contaminated feed or water, Diangelo said. EPM is typically diagnosed postmortem, so veterinarians treat the disease presumptively.
The FDA has approved three drugs for the treatment of EPM, but they work by minimizing the infection and preventing its progression, not by killing the parasite.
Diangelo has been looking for behavioral indicators of EPM this summer, along with her research mentors Dr. Katy Proudfoot, assistant professor and extension veterinarian in animal behavior and welfare, and Dr. William Saville, professor and extension veterinarian in epidemiology and public health.
Diangelo said that the team’s hope is to identify consistent behaviors of EPM-infected horses by closely observing video footage and client records of both affected and non-affected horses, which would help to confirm the diagnosis give more clues to clients that something may be wrong. It’s important that the researchers pay very close attention to abnormal behaviors, and recognize that one behavior may not indicate a certain condition.
“I’m excited that I am familiarizing myself with the equine world,” Diangelo said. “Studying animal behavior is very important in this field.”
Her study is being funded by the Ohio State Racing Commission, and she presented her findings at the annual Merial-NIH Veterinary Scholars Symposium, held this year at UC Davis July 30 – Aug. 2.
Testing therapeutics on feline lung cancer
Second-year student Dylan Burroughs is working on some of the world’s first research on Feline bronchioloalveolar carcinoma (BAC), a form of lung cancer.
The best method for researchers to study BAC without running tests on a cat is to use a live model of the cancer, called a cell line. Worldwide, there is only one feline BAC cell line available, so he and his mentor Dr. Gwendolen Lorch, assistant professor in Veterinary Clinical Sciences, had to wait a while to acquire it for their research.
The team used the cell line to test different concentrations of drugs and how they work in controlling the cancer. They also measured gene and protein expression levels to know what cell regions should be targeted during treatment.
It is typical in human lung cancer for the epidermal growth factor receptor (EGFR), a protein that takes part in cell communication, to be overexpressed. The overexpression of EGFR and related genes leads to an overabundance of cells, which could play a large role in causing the cancer, Burroughs said. In an attempt to stem the excess cell growth, Lorch and Burroughs are testing the effect of EGFR inhibitors on the feline BAC cell line in addition to standard cancer-treatment drugs.
In cats, this type of cancer tends to metastasize - or spread - to the paws. This complicates the effectiveness of treatment options because the tumors are growing in complex patterns that are hard to recognize and target.
The results of the study could potentially help human lung cancer research, but the team is mainly working on establishing normal values for feline BAC that will guide future scientists. They are also focused on understanding the method in which the tumors are able to spread from the lungs to the paws.
Burroughs’ study is being funded by the National Institute of Health, and he presented his findings at the 2015 Merial-NIH Veterinary Scholars Symposium at UC Davis.
Efforts continue to eliminate rabies in Ethiopia
Up to five students in the Veterinary Scholar Summer Research Program are chosen each summer to be supported for international research to work on projects in various parts of the world.
Second-year student Sarah Waibel is spending her summer in Gondar, Ethiopia, to continue the “Rabies Elimination Outreach Project,” which has been funded by Ohio State’s Outreach and Engagement since 2013. Ethiopia has the world’s second-highest human rabies incident rate, which makes it a One Health global preference location to help address and eliminate the disease.
In the U.S. it is commonplace to have our pets vaccinated for rabies – an effort that has decreased the country’s human rabies cases to about 2 or 3 per year, according to the Centers for Disease Control and Prevention. In Ethiopia, there are an estimated 1,456 human fatalities per year according to Rabies and Infections of Global Health in the Tropics (RIGHT), a partnership between Ohio State, the CDC, University of Gondor and Ethiopian Public Health Institute. Dogs are the largest transmitters of the disease, accounting for nearly 95 percent of all human rabies cases in the world, according to the World Health Organization.
Although many wild animals can transmit rabies to humans, we tend to interact with dogs more, especially in Ethiopia where dogs are known to roam freely around communities. Therefore it’s believed that vaccinating the dog population will significantly reduce human rabies cases.
Last summer, the dog population in Gondar was estimated by the RIGHT team, which included another student in the Summer Research Program Alexandra Medley. The 2014 team recorded the number of dogs observed on a representative sample of the streets by surveying people in 13 urban, semi-urban and rural areas of the city. Now that researchers have this information, Waibel will be working on surveillance and monitoring of rabies cases in Ethiopia to better understand what the effective vaccination rate of dogs is to create widespread immunity, she said.
Waibel will additionally be working with the CDC on surveillance monitoring of reported bites and rabies cases in Ethiopia. She’s also studying Mycobacterium bovis, a bacterium that causes tuberculosis in cattle. Humans can contract the disease by drinking unpasteurized milk, which is a common practice in Ethiopia. Her principal advisors are Dr. Wondwossen Gebreyes, professor in Veterinary Preventive Medicine and Director of Global Health Programs for the College of Veterinary Medicine and Dr. Jeanette O’Quin, clinical assistant professor in Veterinary Preventive Medicine.
“I’ve always had a fascination in finding out how and why things work,” Waibel said.
She will be discussing what she and her team found at the Third International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in Thailand this August.
The effort is shared by many partners, including the Ohio State Colleges of Veterinary Medicine, Food, Agricultural and Environmental Sciences, and Public Health; the University of Gondar; Ethiopian Public Health Institute; U.S. Centers for Disease Control and Prevention; Federal Ministry of Health and Agriculture, Ethiopia; Ethiopian Wildlife Conservation Authority and the Pan African Union Vaccine Institute.
Students Marisa Maglaty and Alex Diedrich study genes involved in cancer formation
Second-year students Alexander Diedrich and Marisa Maglaty are inspecting genes that are scientifically correlated with the development of various cancers.
Irregular cell cycles, such as the loss of control over cell growth or cell death, underlie many human and animal cancers.
Maglaty is studying the gene E2F8, a member of a larger family of genes called E2F, which is vital to coordinating progression through the cell cycle. E2F8 differs in structure from other E2F genes, Maglaty said, and she and her team are marking its locations throughout the cell cycle using a mouse model. This technique allows for observation of which genes and proteins E2F8 directly interacts with. Understanding the specifics of these processes is yet another step in the fight to cure cancer.
“The more knowledge we gain through basic discoveries, the more we help humans and animals,” Maglaty said.
Diedrich's research focuses on PTEN, a gene that is widely expressed throughout the body, and its role in endometrial (uterus lining) cancer. If functioning correctly, PTEN works as a tumor suppressor, possibly preventing cells from growing and dividing too rapidly. Mutations of the gene are believed to be a step in the formation of many cancers.
Cancer of the endometrium occurs more frequently in developed countries, and has the highest incidence rate of gynecologic cancers in U.S. women, according to the Centers for Disease Control and Prevention. Diedrich will gain a better understanding of the tumor-suppressing effects of PTEN in female mice by measuring the degree to which certain genes are being expressed during stages of the estrous cycle (a mouse’s menstrual cycle).
Diedrich and his team hypothesize that anything that changes the normal function of the estrous/menstrual cycle could be a risk factor for developing endometrial cancer, since PTEN is important in regulating these cycles. For example women who take tamoxifen, a drug that treats breast cancer, often develop endometrial cancer later in life, Diedrich said. They think this may be because tamoxifen alters hormone signaling.
“Oncology research tends to flow across species,” Diedrich said. “So although this study focuses on human medicine, it feeds back into veterinary medicine.”
Both of the students are working under Dr. Gustavo Leone, professor in the College of Medicine’s Department of Molecular Genetics .The research teams aim to evaluate how these genes perform in combination with mice’s normal physiology, as opposed to in vitro, Leone said.
Scientists have a good idea of how E2F8 and PTEN operate throughout cell and estrous cycles, and this study will give them concrete evidence to confirm existing hypotheses.
“We’re pretty sure of where the genes should be, and when,” Leone said, “But we haven’t actually seen them there.”
Naturally occurring spinal cord injury in dogs guides medical research
To study spinal cord injury (SCI) in humans, some researchers induce the condition in rats or mice. But at the Veterinary Medical Center, third-year student Andrew Muir and his mentor and veterinary neurologist Dr. Sarah Moore have the opportunity to study dogs that come in with naturally occurring SCI for treatment.
Their research is specifically focused on a certain group of cells that surround the central canal of the spinal cord, called ependymal cells. Scientists have found that these cells naturally react to the trauma of SCI by taking on stem cell properties and producing new cells, which then travel to the location of the injury.
Unfortunately, the physiological response doesn’t generate enough support and protection to lessen damage. Hypothetically, if the ependymal cell responses could be manipulated after SCI, animals (and people) may recover better following injury.
Muir and Dr. Moore are identifying and categorizing different cell types in the ependymal layer of the spinal cord from clinical samples of dogs with SCI, they said. Muir uses a technique called immunohistochemical staining to define and characterize the cells.
Several methods of guiding cell behavior have shown promise of improving recovery in rats with SCI, Moore said, but not much is known about how these cells work in dogs.
Classifying these cells will create data that can be used to understand which regions should be targeted in different SCI cases. This should lead to the development of possible therapeutic methods so that one day, more effective medical intervention can be used to treat both animal and human patients with SCI.
“I knew I wanted to do research in neurology,” Muir said. “I’m getting a better understanding of veterinary research and what a career in academia could be like.”
Understanding cellular processes behind most common form of equine laminitis
Olivia Hegedus, second-year student, and Dr. James Belknap, professor of equine surgery in the Department of Veterinary Clinical Sciences, want to understand more about equine metabolic syndrome-associated laminitis (EMSAL), which is the most common type of equine laminitis according to the National Library of Medicine and Institute of Health and the American Association of Equine Practitioners.
"I’ve tried getting into a little of everything; food animal medicine, small animal medicine,” Hegedus said. “But equine medicine was what really fueled my fire.”
Equine metabolic syndrome, or EMS, is similar to human metabolic syndrome, and can lead to insulin resistance in both humans and horses, predisposing them to disease, Hegedus said. However, the diseases associated with metabolic syndrome are quite different in horses than in humans. Whereas cardiovascular disease and diabetes are reported in people, laminitis occurs in horses. Laminitis can cause severe injury, pain and lameness through damage to digital laminae, connections between the 
hoof and bone. When unchecked, laminitis can lead to acute lameness, leaving owners little choice besides euthanasia.
Scientists know that cellular signaling, or how cells interact with one another to perform vital actions, is where the problem lies, but haven’t yet found the exact routes in which the disease forms and spreads.
Belknap and Hegedus have directed their attention to identifying the specific cellular signaling pathways involved in the progression of EMSAL. Understanding how it is caused will lead to the development of therapeutics that can block the disease-causing processes.
Hegedus grew up around horses, she said, and chose this research area due to her interest in equine medicine. The study is funded by the U.S. Department of Agriculture.
“I wanted to challenge myself,” she said. “It’s been a great experience so far.”
Third-year student one of five in nation to receive AVMA/AVMF funding for research
Several students in the college’s Veterinary Scholar Summer Research Program are continuing their research from last year, such as third-year student Katherine Bachman, who’s studying a bacterium that causes Salmon Poisoning Disease (SPD) in dogs.
Bachman is one of five veterinary students in the nation to be chosen to receive funding from the American Veterinary Medical Association/American Veterinary Medical Foundation. Each veterinary college can only nominate one student to receive the AVMA/AVMF stipend.
SPD is generally only found in dogs that live near the west coast, but it’s potentially fatal. They acquire it through ingesting certain types of raw fish and sea life, such as salmon, that are infected with Neorickettsia helminthocea, the SPD-causing agent.
For the second summer, Bachman and Dr. Yasuko Rikihisa, professor in the Department of Veterinary Biosciences, are looking into the mechanisms of the bacterium. Their research focuses on better understanding the nature and survival of N. helminthocea and in turn, the diagnosis of SPD. Their work will involve lab work such as cloning and purifying, Rikihisa said, giving Bachman great hands-on experience.
Bachman said that choosing a mentor and subject area was easy for her, since she knew what she was drawn to. “I’ve always been interested in academia and research,” she said.
Student searches for better method to detect flu in swine
Each summer, veterinarians from Ohio State go to state and county fairs and exhibitions to collect samples from pigs, which they test for influenza A virus. The virus can be transmitted from swine to humans and vice versa, usually through close contact, and poses a threat to both species’ health.
Second-year student Christie Hammons is searching for an improved material for collecting samples, which can be done by wiping the snout of a pig to collect mucus for testing.
Hammons and her mentor, assistant professor Dr. Andrew Bowman, are testing six non-woven fabrics by inoculating them with the influenza A virus to measure how well they can recover the virus from each fabric.
They are attending agricultural fairs in the Ohio and Indiana regions this summer to collect samples from swine snouts in order to test for the presence of influenza A virus.
Although she’s never worked with swine, Hammons said she’s interested in the research because she’s always been interested in diseases that affect both humans and animals, as well as vaccination research.
“I hope to practice and improve my lab skills specific to viruses and sampling processes,” she said.
The research team is currently using cotton gauze to wipe the pigs’ snouts as they test for influenza A virus, Hammons said, but the material isn’t ideal for diagnostic testing. They’ve previously tested alternative fabrics, but this is first time they’re studying a variety of non-woven fabrics, in hopes of identifying a better technique.
Read more about the Animal Influenza Ecology and Epidemiology Research Program’s swine testing.
Student explores cryopreservation methods for canine, feline T cells
Cryopreservation, the process of freezing cells or tissues to sub-zero temperatures while conserving function, has become extremely useful in medical research. While there are several standardized techniques for freezing human material, the methods for other mammalian cells aren’t yet perfected.
This summer, second-year veterinary student Yullee Lin and her mentor Dr. Thomas Cherpes, associate professor in the College of Medicine Departments of Microbial Infection and Immunity and Obstetrics and Gynecology, are working on developing cryopreservation methods that preserve the functionality of canine peripheral T cells, which are important for combating infections and tumors.
When using the protocol for freezing human T cells, the canine T cells don’t quite perform at the level seen in fresh samples, Lin said. The dog cells seem to require unique conditions, which and Lin and Cherpes aim to calculate.
Lin became interested in immunology near the end of her undergraduate career, so her research this summer was a natural step, she said. “It’s a different experience from my previous veterinary work, which involved seeing animals in the clinic.”
Cryopreservation plays a big role in modern immunologic research, including vaccination studies, which also interests Lin. The team is also studying methods of cryopreservation for feline T cells. These comparative medicine studies are a focus of Dr. Cherpes' work.
Searching for a correlation between measles vaccine and respiratory syncytial virus
A vaccination can sometimes protect against more than its intended disease or virus, said second-year veterinary student Sarah Linn. One such vaccination, some scientists suggest, is the measles virus vaccine, which may also shield against respiratory syncytial virus (RSV) infections in humans.
RSV is one of the most common causes of lower respiratory tract infections in infants with 3.4 million cases annually leading to hospitalization in children under 5, according to a study published in the National Library of Medicine. Currently, there is no RSV vaccine available.
Linn and her mentor Dr. Stefan Niewiesk, professor in the Department of Veterinary Biosciences, are examining this relationship more closely as part of the Summer Research Program. Linn and Niewiesk are using a cotton rat animal model to test the measles vaccine in the presence and absence of maternal antibodies. This is so they can see if resistance to RSV infection occurs via the measles vaccine and if it does occur, what measurable effects maternal antibodies can have on resistance in addition to measles vaccination.
Niewiesk was contacted by a group from Denmark that found the measles vaccine protected against RSV infection in human infants through an observation study, he said. This prompted him to perform the study, which will hopefully provide experimental evidence of the connection between measles vaccination and RSV.
Linn said she’s had some experience with pathology research in the past, and is highly interested in working with an animal model to understand human disease. She hopes to pursue a research career.
“I hope for her to gain an understanding of research and the science behind it,” Niewiesk said.
Looking for alternatives to antimicrobial treatment
As the issue of antimicrobial resistance becomes more prevalent, the dairy industry is under more pressure to limit their use of antimicrobials.
Another problem with these drugs is that when organic dairy farmers use them to treat a sick cow or calf, they can no longer sell the animal’s milk as “organic.” This has led veterinary researchers to look for alternative treatments that would reduce the need for antimicrobials.
Second-year student Keirsten Harris spent her summer at Aurora Organic Dairy, an organic dairy farm in Colorado, evaluating alternative methods for treating neonatal diarrhea in calves. This condition is the leading cause of mortality in calves said Dr. Greg Habing, assistant professor in the Department of Veterinary Preventive Medicine. Harris and her research team tested the effectiveness of lactoferrin, a protein found in milk, saliva, tears and other bodily fluid, and garlic extract in treating neonatal diarrhea in approximately 600 calves. Both substances are known to have naturally occurring antibacterial properties.
Lactoferrin and garlic extract are sometimes used as supplements in treating diarrheic calves, Habing said, but prior to this study the individual success of these substances has not been measured on a large scale. Calves were randomized into three groups: one that was given electrolytes only, one that was given lactoferrin and electrolytes and one that was given garlic extract and electrolytes. If a calf was getting progressively sicker, the team would resort to antimicrobial treatment in hopes of saving its life.
The data from each group is being compared in terms of case mortality rate and how many times antimicrobials were used. This will indicate which alternative treatment - lactoferrin, garlic extract or neither - performed the best in managing neonatal calf diarrhea.
"This summer I performed hundreds of physical assessments and blood draws," Harris said. "It was great clinical experience, and I got to see just how much day-to-day work goes into managing a farm with nearly 12,000 dairy cows."
Student studies prostate cancer at canine and human levels
Second-year student Rachael Camiener always knew she wanted to be a veterinarian. During her undergraduate years, she found she also wanted to pursue a career within the field of cancer research.
This summer, as part of the Summer Research Program, Camiener is studying prostate cancer in dogs. Dogs are the only animal other than humans that develop prostate cancer, said her mentor Dr. Thomas Rosol, though they suffer it less frequently.
Camiener and Dr. Rosol, professor in the Department of Veterinary Biosciences, are investigating gene expression in canine prostate cancer cell lines to form a model that mimics human prostate cancer, to better understand the disease and its means of progression.
They are inserting certain dog genes into their cell lines and will select the correct configuration. With the right form, they can begin studying innovative methods to treat the cancer, which could potentially benefit human medicine
Understanding more about how prostate cancer begins and spreads in dogs will help future researchers to find appropriate treatments, preventive measures or a cure.
“It’s difficult to appreciate what’s gone into research until you actually do it yourself,” Dr. Rosol said. “I hope for Rachael to understand the process of research, and how new knowledge is generated.”
Student studies Wobbler’s Syndrome
Elizabeth Helffrich, third-year veterinary student in the Summer Research Program, wanted to choose a mentor and research area that would push her to think and work to the best of her ability.
“Veterinary medicine wasn’t always all about the animals for me,” Helffrich said. “I love animals, but I also love the science aspect and having a chance to make an impact in the field of veterinary medicine.”
She’s getting the research experience she wanted this summer, by studying the mechanisms of cervical spondylomyelopathy, also known as Wobbler’s Syndrome.
Wobbler’s Syndrome is a neurological disease that occurs in dogs and affects the spinal region, making their gait weak or unsteady, among other symptoms. The disease doesn’t have a known cure, Helffrich said. Dogs that get treatment have a better quality of life, but die in the same amount of time as dogs without treatment.
Helffrich and her mentor, assistant professor of neurology and neurosurgery Dr. Ronaldo da Costa, are following up on evidence that apoptosis, or Programmed Cell Death, may play a role in the formation of Wobbler’s Syndrome. They aim to identify the specific defective processes that cause the disease, in hopes of finding data that can eventually lead to a cure.
“One of the most exciting aspects of this research is the potential of discovery,” Helffrich said.
Student changes pace for second year of research, studies pet stress at vet's office
Third-year veterinary student Michelle Forman has always been fascinated by the scientific research process. Last year in the Summer Research Program, her research involved gorillas, and this year, it surrounds the common veterinary visit.
Many people have experienced the stress that a pet can undergo during a visit to the vet’s office. So for many years, the veterinarians in community practice at Ohio State have tried to combat the stress of their animal patients by offering them delicious treats, such as peanut butter or spray cheese. This technique helps relax and distract the pets during procedures such as exams, vaccines and blood draws.
But do these tasty foods have any adverse effects on animals? Forman and her mentor, Dr. Susan Barrett, clinical assistant professor, aim to figure that out in their study.
Sometimes pets experience gastrointestinal stress after going to the vet, Forman said, but she and Barrett aren’t sure whether it’s from stress, food or some other factor, since it has never been studied or quantified before.
They are distributing anonymous surveys to clients to get individual opinions and data on various aspects of handling methods in veterinary visits, including whether or not GI disturbance occurred. Their results could help veterinary offices be more effective in the future, and prevent some pet stress, too.
Student Kanyon McLean uses computer-based models to research disease that threatens cheetahs
Kanyon McLean, third-year veterinary student, isn’t having a typical summer; she’s studying the transmission of amyloidosis in America’s captive cheetah population as part of the College of Veterinary Medicine’s Veterinary Scholar Summer Research Program.
Cheetahs with amyloidosis accumulate misfolded proteins, which can disrupt vital organ functions. The disease poses a serious threat to the already endangered species, McLean said.
McLean and her mentor, Dr. Rebecca Garabed, are using computer software to develop models to try and determine how amyloidosis is transmitted between the cats. The study is titled “Amyloidosis in cheetahs: Genetic or transmissible." Garabed, associate professor in the Department of Veterinary Preventive Medicine, specializes in computer-based modeling of infectious diseases. McLean’s simulated cheetahs can test many hypotheses about the disease without having to conduct stressful procedures on real animals.
What McLean will be using to test long-standing hypotheses about the disease is data; a lot of it. She’s been trained in the programming and other technological skills that the project demands, and will be working with her digital cheetahs through August. The team will look closely into the genetics of cheetahs, McLean said. The project will examine how they (and other factors) might explain the occurrence of amyloidosis in order to keep cheetahs healthy in the future.
“It’s a unique project,” McLean said “Often times cheetahs are very good at hiding when they’re sick. So by the time their illness is known, it’s too late.”
Student studies harmful parasite found in coyotes and prey
Devinn Sinnott, third-year veterinary student in the college’s Summer Research Program, has been studying the fecal samples of coyotes in Ohio to learn about the parasite Hammondia heydomi in her study “Prevalence and role of prey species on Hammondia heydomi infection in coyotes of southeastern Ohio."
To understand more about how H. heydomi is transmitted, Sinnott and her mentors - Drs. Rebecca Garabed, Antoinette Marsh and Karla Moreno-Torres – will also be studying samples from coyotes’ common prey. They will extact parasitic materials from positive samples, which will come from animals in southeastern Ohio, Sinnott said, due to the variety of wildlife.
“It’s a unique area to study,” she said. “You have farms with livestock, native wildlife and The Wilds all in the same region.”
H. heydomi is a single-celled parasite that must live and reproduce inside an animal cell to survive. Due to their hunting and eating habits, coyotes often host the parasite, which infects the intestinal tract.
Marsh and Moreno-Torres, assistant professor and graduate teaching associate respectively, say the research will be great experience for Sinnott in terms of genetic analysis, writing, and reaching out to colleagues. “You can’t research in isolation,” Marsh said.
Sinnott’s research is funded by a stipend from the Merial Veterinary Scholars Program, and she will present her findings later this summer at the 2015 Merial National Institutes of Health (NIH) Veterinary Scholars Symposium at the University of California-Davis.
