Advancing Translational Cancer Research

A Veterinarian from the Beginning

Dr. Heather Wilson-Robles in her lab
Dr. Heather Wilson-Robles in her lab

Dr. Heather Wilson-Robles has known since she was a young child that she wanted to work with animals. “In kindergarten,” she said, “I had the teacher help me spell ‘veterinarian.’ I’ve never wanted to do anything else.” Born and raised in Memphis, it was only natural that Wilson-Robles’ journey to fulfill her dreams would begin at the University of Tennessee, where she received her doctorate in veterinary medicine (DVM). With her DVM in hand, she accepted an internship at the University of Minnesota. Following her internship, Wilson-Robles went on to complete a residency in veterinary oncology at the University of Wisconsin-Madison (UWM). While at UWM, she met the love of her life, Dr. Juan Carlos (JC) Robles Emanuelli. In 2007, they both accepted positions at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), and shortly thereafter married. “We decided that after Minnesota and Wisconsin, anything below the Mason-Dixon line would be fine with us,” joked Wilson-Robles.

Wilson-Robles has since made a name for herself as one of the major players in veterinary oncology. She currently serves as associate professor in the Department of Small Animal Clinical Sciences (VSCS) and has been named the first Dr. Fred A. and Vola N. Palmer Chair in Comparative Oncology. Her husband, JC, recently lost his battle with cancer.

Inspiration to Study Medicine

Along with her life-long desire to work with animals, Wilson- Robles was also inspired to study medicine during her early days in Catholic grade school in Memphis. “My school had a connection with Le Bonheur, the children’s cancer center in Memphis,” Wilson-Robles explained. “A lot of kids would come from all over the world and they were able to go to school there, free of tuition while they were undergoing treatment at Le Bonheur.” Having many classmates undergo cancer treatments gave Wilson-Robles early insight into cancer and terminal illness. With first-hand exposure to pediatric oncology, Wilson-Robles became interested in the various treatments her classmates underwent. “I watched what a lot of the kids in my class went through-and some of them died-and I thought there’s got to be something better we can do.” Despite her interest in improving oncology care for children, Wilson-Robles knew she was better suited to a career in veterinary medicine. “I knew I could never do pediatric oncology,” she said. “I just don’t have the stomach for it. It takes a special kind of person.”

Notwithstanding her reluctance to pursue a career in pediatric oncology, Wilson-Robles would embark on a career that would provide invaluable research and medical discoveries to those children suffering from pediatric cancers. She would go about it in an unorthodox way but would come to realize that her patients-the canine ones-were immensely useful in the treatment of children with cancer.

Two Kinds of Research

In her research at Texas A&M, Wilson-Robles draws a distinction between the two different foci of her work. Splitting her time between benchtop and clinical research she is able to work on both sides of veterinary medical research. She describes her benchtop research as “working with cell lines, working with mice, signaling pathways, and a lot of work with genetics.” Largely responsible for creating proofs-of-concept for a variety of drug therapies and genetic studies, Wilson-Robles’ benchtop research often consists of “cells growing in a flask in media so it looks like pink soup. They’re growing in there and I’ll throw some drug in there and see what happens.”

Despite her cavalier description, Wilson-Robles’ benchtop work is exacting and crucially important to the success of her clinical trials. She is ever aware that the “pink soup” she’s testing for genetic anomalies may hold the key for a new treatment for a type of cancer.

Constantly vigilant and on the lookout for potential new uses for drugs, Wilson-Robles works with drugs and drug companies to test pharmaceuticals in various clinical situations to deter- mine their effectiveness in animals. Her benchtop research informs the clinical research. Having experience in both types of investigative techniques makes Wilson-Robles a premier scientist of veterinary oncology with an exceptionally comprehensive research background.

Expounding on the differences between benchtop research and clinical research, Wilson-Robles explained that laboratory work allows the researcher to tweak experiments and try new approaches based on results. “But in a clinical protocol,” she cautioned, “you follow it to a T.” The strictness of clinical protocol leaves very little room for experimentation or improvisation, which is why scientists like Wilson- Robles who are experienced in both benchtop and clinical research are particularly valuable. “There is always a place for discovery,” Wilson-Robles said, addressing the importance of benchtop research. She went on to say, “There are tons of people doing discovery on the human side and veterinary side. But there aren’t many people-a handful of us nationally-that do the clinical trials to the level that we do here at Texas A&M.”

This combination of research skills allows for a more cohesive research study and perhaps a more successful clinical trial. It is important to Wilson-Robles that her research at either end of the spectrum informs the rest of her work. “I do the initial benchtop work to figure out if a certain drug will block a pathway to make a difference,” Wilson-Robles explained. “And if it does, the next step is a clinical patient.”

The patients Wilson-Robles uses for her clinical trials are nearly all client-owned dogs with naturally occurring cancers, and the research aims to treat their disease and prolong their lives. Much of Wilson-Robles’ work focuses on tumor-initiating cells. She describes tumor-initiating cells as “the worst of the worst” by explaining that all cancer cells are not created equal.

The tumor-initiating cells are those that survive chemotherapy and radiation and continue to proliferate.

It is these cells and their uniqueness that make cancers so difficult to treat. “These cells are drug resistant, radiation resistant, and they don’t replicate as quickly as the other cells do, so they’re much less sensitive to other factors,” Wilson-Robles explained.

Her work in dogs harkens back to her early interest in pediatric oncology because, as she said, “Dogs get pediatric cancers.” Working with dogs in clinical trials has allowed Wilson-Robles to contribute to important research in the human pediatric oncology field as well.

“Heather is an amazing scientist and clinician whose work will change the way oncologic diseases are treated in domestic animals and people,” said Dr. Jonathan Levine, head of VSCS. “More importantly, she is an amazing person who understands that excellence is about character and perseverance.”

 

Mentors Making a Difference

Dr. Heather Wilson-Robles
Dr. Heather Wilson-Robles

Focused on a course of study in veterinary medicine, Wilson-Robles met Dr. Alfred Legendre, professor of medicine in the Department of Small Animal Clinical Sciences in the College of Veterinary Medicine at the University of Tennessee, during her senior year there. Legendre quickly became a mentor for Wilson- Robles and offered important advice when it came time for her to choose her next step. “He helped me set the path I needed to take and I helped him with some research projects,” Wilson- Robles recalled. “He introduced me to clinical research and that’s really where it started.” Still working at the University of Tennessee despite being retired, Legendre remains an important influence in Wilson-Robles’ career. “He’s one of the loveliest men you’ll ever meet,” she said. “He’s supposed to be retired now, but he can still be found wandering the halls and helping out at the University of Tennessee.”

Though most of what she has accomplished in the veterinary oncology field is due to hard work and dedication, Wilson-Robles does acknowledge the importance of serendipity in her career. “One of the best things that ever happened to me was the match at the UWM, for an oncology residency,” Wilson-Robles stated. Through that match, she met Dr. David Vail, professor of medical oncology at the University of Wisconsin School of Veterinary Medicine, one of the “father figures of modern veterinary oncology.” Through Vail, Wilson-Robles was introduced to clinical trials and gained an understanding of how the research and discovery in these trials could translate to human medicine. “He’s a mentor, but he’s also a very good friend,” said Wilson-Robles of Vail. The two still keep in touch and Wilson-Robles noted that even after she left the UWM, she continually asks Vail for advice on upcoming clinical trials. “He and my husband played basketball together,” Wilson-Robles said of Vail, underscoring their close connection and mutual respect and support. Another important influence on Wilson-Robles while at UWM was Dr. David Argyle, the William Dick Chair of Veterinary Clinical Studies and the head of the school and dean of veterinary medicine at the University of Edinburgh in Scotland. He mentored her in laboratory research and taught her how to take new targets from the benchtop to the bedside.

“He was instrumental in my decision to be an academician,” Wilson-Robles said.

“It has been a great privilege in my career to train and mentor the next generation of academicians,” Argyle said. “I knew when Heather joined my team all those years ago that she would go on to have a great career as an academic oncologist.”

 

Future of Veterinary and Human Medicine

Dr. Heather Wilson-Robles with Logan
Dr. Heather Wilson-Robles with Logan

Understanding the ways in which dogs contract and react to cancer cells and clinical drug trials gives Wilson-Robles a greater understanding-and hope for-future treatment across the patient spectrum. “We’re all mammals,” she said, explaining that the more species that react positively to a treatment, the more likely it is that the treatment will be a successful therapy for humans. “It’s not just a dog thing,”

Wilson-Robles explained, “If I can show that a treatment works in a mouse and a dog and a rat, then it probably also works in a human. The more species it works for, the more valuable your results.”

Because of the complexity of cancer cells and cell growth, dogs are an excellent metric for trials of possible pediatric cancer treatments. Certain breeds of dogs have extremely high likelihoods of developing cancer. Golden retrievers have an 80 percent chance of developing cancer in their lifetimes, while boxers have an 86 percent chance. In fact, cancer is the number one cause of death in dogs over three years of age, and 25 percent of all dogs will get cancer at some point. While numbers like these are staggering, they are useful to Wilson-Robles who, through her research, has been given the opportunity to perform clinical trials with a number of different breeds of dogs. Such broad research bodes well for eventual human cancer treatment. Cancer in dogs tends to be akin to the most aggressive form of pediatric disease, and so, Wilson-Robles explained, “if we can get something to work on dogs, it will probably work on kids.”

However, Wilson-Robles cautioned, there is a danger in treating cancer-regardless of the species-as a singular disease. “As far as the future is concerned, I think the biggest thing is to acknowledge that there’s never going to be a magic bullet for cancer,” she said. “There’s never going to be one thing that cures cancer. Cancer is a group of diseases, and it is a genetic disease.” Underscoring the importance of personalized medicine, Wilson- Robles has praise for institutions like Baylor College of Medicine that run genetic profiles on tumors in order to better understand and treat specific cases using personalized drug and treatment recommendations. Chemotherapy, the current “catch all” method for cancer treatment, is “fighting fire with fire.”

Wilson-Robles warned of the indiscriminate nature of some forms of treatment, but said, “In many cases, this is still the best option for treatment available.”

Going Forward

Ultimately, the goal for Wilson-Robles and her colleagues in veterinary oncology is to perform research on dogs with an eye toward informing treatment of human subjects.

However, Wilson-Robles finds her work with animals rewarding on its own merits. “Now,” she explained, “we’re in negotiations with T-gen, Colorado State, Ohio State, and the National Institutes of Health (NIH) to do a large national multi-institutional trial looking at drugs given to dogs with osteosarcoma, which would hopefully then lead to approval for the drug for humans.”

Ever passionate about her research and clinical work, Wilson- Robles has found a home at Texas A&M. At the top of her profession- and leading the way in research for veterinary oncology and veterinary medicine- she stands poised to make important, perhaps groundbreaking, discoveries in the years to come.

Texas A&M Develops New Vaccine To Combat Lethal Disease Affecting Captive Parrots

COLLEGE STATION, Texas – Researchers at the Texas A&M; College of Veterinary Medicine & Biomedical Sciences (CVM) have developed a highly effective vaccine against a lethal virus disease of captive parrots. The disease, called Proventricular Dilatation Disease (PDD), results in blindness, heart failure, or intestinal blockage. It is caused by a virus called Avian Bornavirus. Use of the vaccine against this virus prevented the development of disease in captive birds with no obvious adverse effects.

Proventricular Dilatation DiseaseThe investigators-Drs. Ian Tizard, Jianhua Guo, Susan Payne, and Samer Hameed-work at the Schubot Exotic Bird Health Center at the CVM. The research was supported by the Schubot Center and the college. The center is dedicated to conducting research that will improve the health and quality of life of both captive and wild birds. While currently focusing on diseases of parrots, investigators at the center are also studying diseases of water birds, quail, and cranes.

“Proventricular Dilatation disease is an especially nasty infection that kills large numbers of captive birds each year,” said Dr. Ian Tizard, the project leader. “Parrot owners are naturally very distressed when their beloved pet dies in such a manner. The new vaccine is expected to stop the development of this disease and prevent much suffering.”

The next step in the development of this vaccine will be to seek USDA licensure and then to manufacture the vaccine commercially. This will require extensive field-testing to ensure that the vaccine is safe and that it is effective in many species of pet birds. Thus it will take some time before the vaccine becomes available to parrot owners. Current plans are to market the vaccine through avian veterinarians.

The pace of the additional studies will naturally depend upon the resources available. Current resources are limited, so it is difficult to state when this vaccine will be available to parrot owners.

Dr. Dindot Working With Students on Autism Research

Through their own initiative, both Dylan Ritter-a sophomore at the University of Mississippi-and Kathleen Nelson-a high school senior from Illinois-discovered Dr. Scott Dindot’s genomics lab. While their friends took off for vacation and summer fun, they chose to come to Texas A&M University to work on autism research with Dindot in the College of Veterinary Medicine & Biomedical Sciences. Their passion is to advance the knowledge of autistic disorders so that others may benefit in the future.

Dr. Dindot with students

According to the Centers for Disease Control and Prevention (CDC), 1 in 68 individuals have a diagnosis of autism spectrum disorder. Most children are diagnosed when they see a physician. Typically they miss their developmental milestones, but often their parents and other caregivers notice social deficits. Since autism is a spectrum disorder, it varies considerably from individual to individual, but primary signals include social communication deficits, learning disability, and repetitive behaviors.

Ritter and Nelson are interested in autism research because Ritter’s younger brother has Chromosome 15q Duplication syndrome (Dup15q) and Nelson’s older brother has Angelman syndrome, both forms of autism and intellectual disability. Recognizing that both of these young students are exceptional and possess a drive for advancing research in the disorders that have affected their families, Dindot welcomed them into his lab. He was impressed by the drive that brought both students to College Station-away from friends, family, and everyone they know-to help others who have experienced a similar diagnosis.

“Dylan could be doing anything,” Dindot said, “but he’s here. He was awarded a grant from the Autism Science Foundation that supports undergraduate student research. This is an extremely prestigious award, and students from all around the country compete for these funds. The other recipients this year are from Stanford, Yale, and the University of California Santa Barbara. These students are the cream of the crop. This is a national competition. It’s a very competitive, very prestigious award. It’s a credit to Dylan’s drive that he received the grant.”

Ritter – a sophomore at the University of Mississippi – has no connection to Dindot other than the fact that he saw a press release about Dindot’s lab developing a Dup15q mouse model.  He contacted Dindot saying that his brother had Dup15q syndrome, and that he wanted to come help and be involved in the research however he could.

Nelson, similar to Ritter, found Dindot through the Foundation for Angelman Syndrome Therapeutics, which funds two research projects in Dindot’s lab . Kathleen wants to be a physician and was looking for things to do that will help her achieve that goal. Because of her brother’s condition, she asked her family if she could work in Dindot’s lab and learn about what they’re doing.

“Both of these students are very similar in terms of the emotional connection to this work,” Dindot said. “It’s a very personal, extremely important topic. They’ve chosen to pursue this with that in mind. They could be doing anything during their summer break, but they are here at A&M researching the conditions that affect their siblings.  I can’t think of anything more commendable or inspirational.”

EPA Awards Texas A&M Researchers $6 Million Grant to Investigate Environmental Impact on Cardiac Health

COLLEGE STATION, Texas – The Environmental Protection Agency (EPA) has awarded a $6 million grant to fund a multi-institutional collaboration between the Texas A&M; College of Veterinary Medicine & Biomedical Sciences (CVM) and the Bioinformatics Research Center at North Carolina State University (NCSU) investigating the effects of environmental toxicants on human health with a focus on the potential adverse effects on the heart.

Dr. Ivan Rusyn
Dr. Ivan Rusyn

The large project is led by Dr. Ivan Rusyn, professor of veterinary integrative biosciences at the CVM. He and his team will develop and validate a novel approach to studies of chemical safety in both human cells and in mice.

“I am very pleased with the support that the Environmental Protection Agency has extended to the areas of in vitro and computational toxicology,” Rusyn said. “Research and development activities in the center will be directed at improving the scientific basis for decisions and will create solutions that can be immediately utilized by the stakeholders in environmental health sciences: the industry, the non-governmental organizations, and the state and federal regulators.”

According to Rusyn, the growing list of chemical substances in commerce and the complexity of environmental exposures represent an enormous challenge to the regulatory agencies that examine the toxic potential of chemical exposures. Traditional chemical safety testing evaluates only major potential health hazards of concern to human health, such as the ability of environmental chemicals to lead to cancer, cellular damage, or to long-term negative impacts on reproductive health. However, the World Health Organization (WHO) estimates that up to 23 percent of the global incidence of heart disease, a leading cause of death, may be attributable to environmental chemicals. The ability to assess non-pharmaceutical agents for cardiac toxicity testing has lagged behind other advanced efforts to create animal and cell-based models for studies of chemical safety.

“As an institution committed to the One Health initiative, this award from the EPA will significantly strengthen cross disciplinary research aimed at improving the health and well-being of both animals and humans that share the same environmental risks,” said Dr. Robert Burghardt, associate dean for research and graduate studies.

Joining Rusyn on the project team are co-principal investigators Dr. David Threadgill, professor in the Department of Molecular & Cellular Medicine at the Texas A&M; Health Science Center and the Department of Veterinary Pathobiology at the CVM, and Dr. Fred Wright, professor of statistics at NCSU.

“The major outcome of our work will be development and validation of a population-based human and mouse organotypic culture model for characterizing variability in cardiac toxicity,” Threadgill said.

“By adding an inter-individual variability dimension to the studies of environmental chemicals and drugs safety, we enable greater precision in toxicological findings,” added Wright.

The grant will establish the research center with Texas A&M; serving as the lead institution. The long-term objective of the center is to advance the field of environmental health by establishing and validating effective, accurate, and fiscally responsible means for identifying and characterizing cardiac chemical hazards.

“Texas A&M; has a tradition of high-impact research,” said Dr. Eleanor Green, the Carl B. King Dean of Veterinary Medicine. “The opportunity to establish and to lead this multi-institutional research center is a testament to Dr. Rusyn’s excellence and that of his colleagues. It is notable that Dr. Rusyn is one of our President’s Senior Hires supported by the Chancellor’s Research Initiative. This grant not only demonstrates the wisdom of this program but also the fulfillment of the stated goals by these outstanding faculty.”

The project was initiated as the result of recent advances in the development of models of functional cardiac muscle cells. This has led to new prospects for simulating complex chemical outcome pathways in the beating heart. Funding began June 1, 2015 and will carry through May 31, 2019.

CVM Professor Honored with University-Level Distinguished Achievement Award in Research

COLLEGE STATION, Texas – The Texas A&M Association of Former Students (AFS) honored Dr. Mark Westhusin of the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM) faculty with a University-Level Distinguished Achievement Award in Research, one of the highest honors presented by the AFS.

Dr. Mark Westhusin
Dr. Mark Westhusin

“Dr. Westhusin has been an outstanding member of our faculty for many years, and his contributions to veterinary science and the progress he has made in the advancement of animal and human health are immeasurable,” said Dr. Eleanor Green, the Carl B. King Dean of Veterinary Medicine. “We are indebted to him for his unsurpassed excellence in animal cloning and congratulate him for being a recipient of this award.”Westhusin, a professor in the Department of Veterinary Physiology and Pharmacology (VTPP) at the CVM, focuses his research on animal cloning. His laboratory group has successfully cloned more different species (cow, goat, pig, horse, cat, and white-tailed deer) than any other institution in the world, including the first cat and first white-tailed deer.

Westhusin’s most recent work has advanced the knowledge of the role genes play in disease resistance and protein synthesis. The results of his research will lead to improving the quality of protein sources available in developing countries, to the increased safety of the food supply, and to the ability to protect populations of people from devastating insect-borne diseases.

“He is one of the finest and most productive faculty members whom we have had the privilege to work with in our department and college,” said Dr. John N. Stallone, interim head of VTPP. “He is a most worthy recipient of an Association of Former Students Distinguished Achievement Award in Research.”

Each honoree will receive a framed certificate from the AFS along with a $4,000 monetary award. The awards, begun in 1955, recognize outstanding members of Texas A&M’s faculty and staff for their commitment, performance, and positive impact on Aggie students, Texas citizens, and the world around them.

Texas A&M researcher contributes to important public debate concerning biological risks of feedlot dust

Dr. H. Morgan Scott, a veterinary epidemiologist in the Department of Veterinary Pathobiology at Texas A&M University, along with colleagues at West Texas A&M University and Kansas State University, recently participated in an important academic debate concerning biological risks associated with feedlot dust in west Texas. Their views were featured in an April 3, 2015 article posted below. The debate stems from a recent peer-reviewed paper published in the journal Environmental Health Perspectives (EHP); subsequent media coverage of the paper has resulted in a few misleading headlines and news articles concerning the spread of “superbugs.” Dr. Scott and colleagues contend that in the EHP paper several inferences were presented as conclusions, when in reality they remain untested hypotheses. Contrary to much of the media representation of this research, the data do not indicate whether there were any viable bacteria present in the samples; therefore, there is no direct evidence of “superbugs.” The likelihood of non-viable bacterial genes transforming into other living bacteria is of very low probability, and thus the biological risk associated with the dust must be considered extremely low. Ongoing public concerns about antimicrobial use and resistance in animal agriculture continue to this day; an important component of addressing those concerns is healthy debate and discussion among scientists.

Scientists dispute study on antibiotic residues in feed yard dust

By John Maday, Editor, Bovine Veterinarian

In January, we covered a report from Texas Tech University’s Institute of Environmental and Human Health, outlining a study in which researchers detected antibiotic residues, bacteria and genetic material related to antibiotic resistance in particulate matter downwind of Texas feed yards.

The research paper, titled “Antibiotics, Bacteria, and Antibiotic Resistance Genes: Aerial Transport from Cattle Feed Yards via Particulate Matter,” was published in the Journal of Environmental Health Perspectives.

Last week, Michael D. Apley, DVM, PhD at Kansas State University, Samuel E. Ives, DVM, PhD at West Texas A&M University and H. Morgan Scott, DVM, PhD at Texas A&M University released a white paper citing concerns over the conclusions listed in the Texas Tech report.

The three research veterinarians focused on issues of bacterial viability, likelihood of bacterial re-population and the concentration of antimicrobials found in the feed yard particulates.

“In this paper, many inferences are presented as conclusions when in reality they are actually untested hypotheses,” they wrote. Contrary to much of the media representation of this research, the data do not indicate that there are any viable bacteria present in their samples. The likelihood of non-viable bacterial genes transforming into other living bacteria is of very low probability. The antimicrobial concentrations used in this study are not grounded in appropriate air and soil volume concentrations and do not accurately represent the dispersion and dilution of these agents in the environment.” In an interview published this week in the Journal of Environmental Health Perspectives, Dr. Ives says “qPCR techniques only reveal the presence of bacteria, not their viability. That doesn’t translate to transference to the environment and beyond.”


Read the full white paper from Drs. Apley, Ives and Scott.

Treatment of Canine Mitral Valve Disease Shows Promise

COLLEGE STATION, Texas – Mitral valve disease accounts for approximately 75% of all canine heart disease, but a recently finished clinical trial shows that a potential treatment might help. The trial, titled “Evaluating Pimobendan In Cardiomegaly” (EPIC), is the largest clinical study ever to be conducted among dogs with myxomatous mitral valve disease (MMVD), the leading cause of heart disease and heart failure in dogs. It evaluated the effectiveness of pimobendan in delaying the onset of clinical signs of congestive heart failure in dogs with increased heart size secondary to pre-clinical MMVD.

Dr. Sonya GordonA mid-study analysis in mid-February 2015 indicated that pimobendan is clearly beneficial and did not raise any concern over the administration of pimobendan.  Based on these results the interim analysis committee recommended that the study be stopped and the lead investigators-Dr. Sonya Gordon, associate professor in the Department of Small Animal Clinical Science at the Texas A&M University College of Veterinary Medicine & Biomedical Sciences; Dr. Adrian Boswood at the Royal Veterinary College, Veterinary Clinical Sciences, Hatfield, Hertfordshire, UK; and Dr. Jens Häggström of the Swedish University of Agricultural Sciences, Faculty of Veterinary Medicine and Animal Science, Uppsala, Sweden-ended the study as of March 1, 2015..

“I am excited about the results of this groundbreaking study and proud to be a part of the EPIC team,” Gordon said. “The results of this clinical trial have the potential to change the way the most common cause of heart disease and heart failure in the dog is managed on a day-to-day basis by veterinarians around the world.”

The study was a prospective double-blind, randomized, placebo-controlled, international, multi-center clinical study-the so-called “gold standard” of clinical trials. Specialized veterinary cardiologists at 36 trial centers, half of which were in the United States, ran the trial. (The other 18 centers were in Australia, Canada, France, Germany, Italy, Japan, The Netherlands, Spain, Sweden, and the United Kingdom.) The 360 canine patients enrolled in the trial were randomly allocated to either a pimobendan or a placebo treatment group, with 180 dogs in each group. Gordon and her colleagues at Texas A&M saw 16 of those dogs.

Full and final results of the study, which was sponsored by Boehringer Ingelheim, are expected at a later date.

Running for a Cause: How Putting Yucatan Miniature Pigs on Treadmills Helps Fight Heart Disease

If you walk by Dr. Cristine Heaps’ lab on a sunny afternoon in the spring, you may see Yucatán miniature pigs running on treadmills.

Dr. Cristine HeapsHeaps, an associate professor in the Department of Veterinary Physiology & Pharmacology at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), studies the effects of exercise on heart disease using these pigs. Adaptations in the heart during exercise intrigued Heaps, who was involved in athletics from a young age.

Exercise puts demands on a body, causing the heart to beat faster and move blood more quickly through the cardiovascular system. A person with heart disease may be fine while watching a rerun of Survivor; however, after the show is over and the person is sweating like a pig while pushing a lawn mower, he may suddenly have a heart attack.

Risk factors, such as obesity and lack of physical activity, contribute to the development of cardiovascular disease. According to the 2013 Overweight and Obesity Update by the Centers for Disease Control and Prevention, around 50% (154.7 million) of Americans 20 years and older are overweight. As obesity rates increase in other countries, the number of deaths caused by cardiovascular disease will also rise.

So why use pigs in research? A pig’s cardiovascular system functions similarly to a human’s. Likewise, the pig body mimics a human’s in response to exercise; therefore, running pigs with heart disease on treadmills models humans with heart disease exercising.

Arranging for approximately 100-pound Yucatán miniature pigs to run on a treadmill you might see at a local gym is both labor-intensive and expensive, so this type of model is uncommon. In fact, Heaps’ lab is one of the few in the United States using a pig model combining heart disease and exercise.

Researchers elsewhere contact her to collaborate. Dr. Steven Fisher, a physician and recent collaborator from the University of Maryland’s School of Medicine, contacted Heaps to help with his research because she uses this model. “Very few labs have this model,” Fisher said. “Coronary heart disease is very difficult to model.” A recent study by Heaps and Fisher indicates exercise may increase the heart’s sensitivity to drugs such as Viagra. In addition to her recent collaboration with Fisher, Heaps also works with faculty at both the CVM and the Texas A&M Health Science Center.

Often waiting in silence, cardiovascular disease is deadly until conditions are right, such as exacerbation by exercise. This disease has not only severe, often fatal, health implications but economic repercussions as well. Heaps noted, “Billions to hundreds of billions of dollars and productivity are lost to heart disease.”

Pigs

Museum “crusties” Foster Collaboration Between Geneticists and Smithsonian

Museums are a repository of many artifacts collected in times gone by, and the Smithsonian holds one of the United States’ best collections. Its Division of Mammals at the National Museum of Natural History houses a world-class collection of roughly 590,000 preserved specimens, many of which are available to researchers, including Dr. Bill Murphy, a mammalian geneticist in the Department of Veterinary Integrative Biosciences at the College of Veterinary Medicine & Biomedical Sciences (CVM).

Dr. Bill MurphyMurphy’s background in comparative genomics and mammalian phylogenetics helps him determine the ancestral relationships between different groups of species, when they originated, what factors drove them to diversify, and what processes led to their distribution around the globe. In his journey to discover these connections, Murphy has taken advantage of the hard work already accomplished on species collection trips over a century ago.

Since 2002, Murphy has been collaborating with a mammalogist, Dr. Kris Helgen, on the methodology of using museum specimens to extract mammalian DNA. But the practice really advanced in 2008 when the pair started exploring the mammals collection at the Smithsonian, where Helgen is the curator in charge of mammals. Their goal is to use DNA from museum specimens to understand how rare or unusual groups of mammals fit into the mammalian family tree. Murphy brings the genetic component to the collaboration, whereas Helgen brings the curatorial and mammalogy background to help classify and understand mammals more thoroughly.

The field of museum-based genetics had its origins in the early 1990s, according to Murphy. Although many studies with museum specimens have been conducted in the past, Murphy wondered how well DNA could be recovered from these specimens and in large amounts without contamination. Also, he wanted to determine if the new  next-generation sequencing techniques might reveal a more accurate resolution of ancient DNA sequences, as well as larger datasets for phylogenetic analysis. Typically, previous researchers have chosen to extract DNA from the hide or hair of specimens because it is more abundant, but there is an increased risk of contamination from being handled over the years. Using hide samples can also be more problematic because hides are often chemically treated for preservation.

To avoid analyzing DNA from specimens where the possibility of sample contamination is high, Murphy and his team implemented an alternative approach to sampling. “We developed an approach where we extract DNA from the ‘crusties’ as we call them,” said Murphy. “When you examine skulls in museum collections, they are usually pretty clean. But if you look inside the brain case you can actually see tidbits, little remnants of dried tissue that have been sitting there for a 100–150 years. For the most part these tissues have never been exposed to human contact, so we figured there would be less contamination. This approach is also less destructive since museums like to avoid damaging specimens, such as drilling into bones or taking hair and tissue samples, at all costs. No one can tell if you’ve removed a bit of tissue from inside a skull.”

Murphy and his team have found that they can get an extraordinary amount of acceptable and quality DNA from these tissues. And with the new sequencing technologies, Murphy has found that the DNA sequencing is simplified with degraded “crusties” more than if one starts with fresh or frozen tissue.

With this methodology researchers can also reduce or avoid the costs and time associated with trapping animals in the field, applying for permits and permissions, and traveling; they can take advantage of the work done a century before that resides within museums. This method also allows geneticists to access and sequence DNA from extinct species. Murphy is working on such a project with a colleague in South America to extract ancient DNA from extinct ungulate megafauna groups, such as a Toxodon, a rhinoceros-like species that went extinct in the Pleistocene.

Historically, mammals have been classified into small groups and researchers believed that if species share the same morphology, or physical characteristic, they must be related. But with the new sequencing technology, genetics has revealed that parallel evolution, the development of similar physical characteristics in related but distinct species, is happening among the whole mammalian tree. According to Murphy, “Among the 4,500 mammal species identified in 2005, geneticists now believe there are roughly 6,000 species as a result of molecular techniques, but there is speculation that there are probably close to 10,000 species of mammals.”

Murphy has used the technology and museum specimens at the Smithsonian to study colugos, the closest known living relative to primates found throughout the islands of Southeast Asia. “Colugos are one of the most poorly known groups of mammals, and the problem is they are not found in zoos and you can’t sample colugos from across Southeast Asia very easily. So we turned to museum specimens,” said Murphy. He feels that by understanding the genome of colugos, we can understand the genetic transition to primates. In his team’s analysis of 13 specimens in one area alone, it was determined there were probably as many as five or 10 species, whereas it was believed that only two existed.

Murphy and his team’s technique has yielded promising and successful results. “We have not had too many limitations. Most of the samples for which we have attempted DNA extraction have been highly successful. The results have been so promising that we have proposed a much more concerted effort of using only museum specimens to identify the true number of mammal species on Earth,” said Murphy.

However, different museums preserve specimens differently, and their location also affects the quality of the samples. For example, a museum located in a tropical environment has to battle with factors such as mold and bacterial growth, and having temperature-controlled rooms to avoid mold and bacterial growth can help with this. Other elements, such as how specimens are preserved and handled, also have an effect on a sample’s quality.

Since 2008, Murphy has been a research associate at the Smithsonian, and he travels there about once every one to two years. In the company of Helgen, Murphy and his graduate student, Victor Mason, have also visited the American Museum of Natural History in New York and the Raffles Museum of Biodiversity Research in Singapore. Along with studying colugos, the pair has also studied cat species and other endangered species in Southeast Asia. “There are probably many undiscovered, cryptic species in Southeast Asia, and this is an ongoing focus of the collaboration with the Smithsonian,” said Murphy.

“Molecular genetic technologies have rapidly changed the way in which mammals are classified. We can also look at genetic diversity within species 100 years ago and compare them with today to see how human influences have affected their genetic diversity,” said Murphy. The technology and use of museum specimens extends beyond studying mammals and can be utilized to study other species as well.

The National Museum Of Natural History

Dr. H. Morgan Scott: Viewing Epidemiology through a Different Lens

Dr. H. Morgan Scott has ridden his bicycle around the world, but he keeps coming back to College Station. Scott, an epidemiologist and infectious disease expert who taught at Texas A&M University from 2001–2009, has returned to the Texas A&M College of Veterinary Medicine & Biomedical Science (CVM) after a stretch as the E.J. Frick Endowed Professor of Veterinary Medicine at Kansas State University. He will lead the development of the Microbial Ecology and Molecular Epidemiology (ME2) research laboratory at the CVM as a tenured epidemiology professor in the Department of Veterinary Pathobiology.

Dr. H. Morgan ScottDr. Scott didn’t originally plan to be an epidemiologist, however. The Canada native first encountered epidemiology while pursuing a DVM from University of Saskatchewan, when an eccentric professor who incorporated props into each lecture piqued Scott’s interest. Once Scott graduated in 1988 and started working as a practitioner at larger cattle farms, he realized that his veterinary training wasn’t extensive enough to tackle the issues at hand. “These farms had herd health questions that were simple on the surface, but very difficult to answer,” Scott said.

Heading into the Ph.D. program at the University of Guelph in the Canadian province of Ontario, he fully intended to get back into veterinary practice one day. Instead, he turned to epidemiology to explore the best methods of reducing disease burden in animals.

Today Scott is establishing ME2 at the CVM, but at the time, Scott shared that he never envisioned having a lab. “I saw the world as my lab-which is clichéd and naïve,” Scott said. He soon realized that in order to conduct experiments, he needed a controlled area for his research-which he couldn’t outsource. He learned to work with colleagues in different fields to meet his research needs and gain access to other useful and pertinent data.

As it turns out, cross-disciplinary collaboration has become a hallmark of Scott’s career. He began postdoctoral studies in public health and research in risk analysis at the University of Alberta in 1999. While in Alberta, he shared an office with a moral philosopher, a sociologist, a toxicologist, an occupational hygienist, a civil engineer, and an ethicist. “I developed an enormous appreciation for the other aspects of human health, of how humans behave with respect to everything we do,” said Scott. “This also applies to farming and agriculture. People like to say the farming business is entirely economic, but it’s not.”

Now he continues to work with researchers in other disciplines and understands one person can’t be an expert in everything. “Projects end up being more exciting this way. It’s about evaluating what people bring to the table and recognizing you can appreciate each other, which makes science fun,” Scott said. “You read a crazy idea and say, ‘Hey, maybe we can make that work here.'”

Dr. H. Morgan ScottMembers of ME2 study zoonotic disease control to improve food safety and public health. Scott ultimately hopes to reduce resistance to antibiotics among zoonotic bacteria, which can be transferred from animals to humans. He examines and observes how bacteria compete against each other in areas with finite resources, like within an animal’s digestive system. Scott and his team use microbiological and molecular methods to measure whether certain bacteria are resistant to antibiotics. These researchers also use genetic tools including recent moves into whole genome sequencing to observe how one strain of a bacterium is particularly successful at outcompeting others.

Scott’s lab is being stationed in the new Veterinary Research Building annex, and he has filled the 1400-square-foot space with top-of-the-line equipment. His research will be conducted entirely out of ME2 with the assistance of a six-person (and growing) team, which will include CVM graduate students. ME2 receives some of its start-up funding from the Chancellor’s Research Initiative, among others.

“Dr. Scott’s efforts in the laboratory will translate to an innovative and dynamic learning opportunity for our graduate and veterinary students,” said Dr. Linda Logan, former head of the Department of Veterinary Pathobiology. “Learning from his experiences will prepare our graduate students with practical and applied knowledge and skill sets for future roles in government, industry, and academia.”

An integral part of Scott’s work is rooted in communication with the public. During his more than 20-year career, Scott has seen food safety information grow from nonexistent to routine and systematic. He briefly worked as an epidemiologist for the Food Safety Division of the Government of Alberta in 2000, where he learned to use foodborne pathogens as a way to measure whether an intervention was effective. There he helped establish and monitor food safety outcomes; this research involved collecting data on foodborne disease pathogens in particular areas. While there have been some improvements in surveillance on the human side, scientists still don’t know the extent of antibiotic use on the animal side. “Molecular work lets you trace an organism back to its origin, see how it’s changed over time, observe its lineage, and note its acquisition of resistance,” Scott said. “In terms of how we use antibiotics [in animals], we still don’t have any broad and useful national data at this point.”

Scott says that how to use these data to effect policy change isn’t a question for scientists, but rather a discussion for the public. Society has to decide if it wants these data to be used to make informed decisions about the continued use of antibiotics in its food production systems. At that point, discourse leaves the scientific arena and enters into political debate. For example, in an October 2014 interview for PBS Frontline, Scott discussed how his team noticed that cephalosporin, an antibiotic, was losing its effectiveness among Gram-negative bacteria, which can have adverse effects on human health. When researchers tried using an alternative antibiotic, tetracycline, to reduce resistance to cephalosporin, the resistance to cephalosporin actually increased. “If someone wants me to detail the best way to use antibiotics, I can’t actually give them that answer at the moment,” Scott said. “The timeline of resistance development spans decades, and decisions on how to use antibiotics need to project at least that far into the future.”

With his interdisciplinary approach to research, Scott says being at a large, multiservice university like Texas A&M is very appealing. On such a large campus, there are ample opportunities to collaborate with people working nearby. He recalls that even when he first started at Texas A&M in 2001, he received nothing but support for his research. “I always have lots of encouragement to pursue my interests,” Scott said.

Scott’s areas of expertise complement the CVM’s One Health Initiative, which explores the connections between human, animal, and environmental health. He notes that measures taken in animal agriculture affect human health and vice versa. “My work sits at the intersection of agriculture, human health, and human activity in general,” Scott said.

In addition to leading the ME2 lab, Scott will teach graduate courses on risk analysis as well as disease detection and surveillance. He is the immediate past president of the Association for Veterinary Epidemiology and Preventive Medicine and an advisor to the World Health Organization Advisory Group on Integrated Surveillance for Antimicrobial Resistance. His wife, Dr. Cheryl Herman, also returns to the CVM as a clinical associate professor of anatomy. They continue to cycle when they can find the time.