COLLEGE STATION, Texas – When billions of songbirds make their yearly trip from their winter homes in South and Central America to North America, they are not alone. Some migratory songbirds pick up hitchhikers-specifically ticks, according to a study from researchers at the Texas A&M; College of Veterinary Medicine & Biomedical Sciences (CVM) and the Smithsonian Conservation Biology Institute’s Migratory Bird Center.
Researchers screened songbirds in the springs of 2013 and 2014 at stopover sites along the Gulf of Mexico’s northern coast, where birds rest and feed during their northward migration. From this sampling, the study’s investigators estimated the number of neotropical ticks from South and Central America making their way into North America on songbirds as well as which birds were more likely to carry ticks.
The study, published in Applied and Environmental Microbiology, found 3.56 percent of the 3,844 birds sampled carried ticks, the majority of which were neotropical tick species. While this percentage may seem small, when extrapolated to all migratory birds making their way into North America annually, the researchers estimate over 19 million neotropical ticks are imported each spring.
“Even though birds carrying exotic ticks into Texas was a rare event-about 3 percent of the birds we sampled-this equates to a really large number of ticks when you consider that billions of birds move along this migratory path each spring,” said Dr. Sarah Hamer, assistant professor in Veterinary Integrative Biosciences at the CVM and an author on the study.
These ticks were not picky about which bird species they used as hosts. In fact, 36 of the 85 bird species sampled were tick carriers. “These ticks are generalists as larvae and nymphs,” said Hamer. “They can feed on a lot of different types of birds.”
Birds that were more likely to pick up ticks were those that foraged closer to the ground, according to the study. Ticks often drop onto the ground to enter their next life stage-from larva to nymph or from nymph to adult. This is when ticks seek a new host, making birds closer to the ground become more susceptible to becoming infected, said Hamer.
This tick transport could be cause for concern because of the pathogens ticks can carry. Of the ticks found of migratory birds, 29 percent carried one or more species of the bacteria Rickettsia, including some responsible for diseases such as Rocky Mountain spotted fever.
“What we found is that there are lots of diverse Rickettsia species found in ticks removed from migratory birds,” said Hamer. “Some are endosymbionts that are not known to have a negative impact on the tick or a human or an animal, but others are recognized pathogens, like spotted fever group Rickettsia species that certainly can cause disease in people and animals if they get the opportunity to infect them.”
Additionally, researchers point out that many of the tick species found in the study are not native to the United States. “Most of these species are not typically found in the U.S., except one- Ambylomma maculatum, the Gulf Coast tick,” said Lisa Auckland, a research associate at the CVM and an author on the study.
Currently, most of the tick species found in this study do not have known established populations in the United States. However, researchers caution that ticks could establish populations in the United States in the future, given an ever-shifting environment and climate change.
“It’s good to be aware of this because our environment is constantly changing,” said Hamer. “Maybe some of those changes may result in an environment that’s warmer and more receptive to the establishment of these exotic ticks. Then, we may have new medical problems on our hands.” Further research is also needed to understand what happens after neotropical ticks make their way to the United States, she said.
When a loved one is diagnosed with cancer, the first questions that often come to mind are, “why did this happen to them,” and “what can I do.” Faced with this very situation, Dr. Ivan Ivanov, clinical associate professor in bioinformatics at the Texas A&M; College of Veterinary Medicine & Biomedical Sciences (CVM), began a journey helping advance research that one day may be able to answer those questions.
To create new knowledge in this multidisciplinary environment requires the ability to ask questions and design
studies that are based on scientific principles, and communicating that complexity requires a common foundation-a foundation Ivanov is helping to build. However, it was more than an interest in collaboration and complex systems that led Ivanov to his research in cancer biology; it was a series of life events.
The Journey Begins
When Ivanov was a middle school student in the former communist country of Bulgaria, his teacher suggested he apply to a national high school that specialized in mathematics. After speaking with his mother, he decided to apply and was accepted after taking two required entrance exams.
“From there, I went to the university, and I was successful because the teachers I had at the high school were not ordinary teachers,” Ivanov said. “They were Sofia University professors. They ignited one’s curiosity, and that was very exciting.”
While still a mathematics student at the university, Ivanov’s former father-in-law was diagnosed with cancer and he deteriorated quickly. “I was thinking how he could be such a great man, a nonsmoker, a good father and husband, a hard worker-he does everything right, and then he’s hit by this disease,” said Ivanov. “He died after two months. I carried him around in my hands because he lost 50 percent of his weight. I wondered how this could be helped. I was just a mathematician, a mathematics student. I didn’t know anything about biology, and it was very complicated to me.”
Years passed after his former father-in-law’s death and Ivanov left Bulgaria, finished his Ph.D. in mathematics at the University of South Florida, and, after a one-year postdoctoral position at Syracuse University, arrived at Texas A&M; University for a postdoctoral fellowship in the mathematics department.
Once at Texas A&M;, Dr. Edward R. Dougherty, a distinguished professor in the Department of Electrical and Computer Engineering, asked Ivanov if he would be interested in doing some work in cancer biology. Still asking himself, “Why did this happen to my father-in-law, and what can I do about it?” Ivonov began his journey with Dougherty.
Dougherty, who also has a Ph.D. in mathematics, explained some of the problems that cancer investigators were working to solve. He asked Ivanov to write a brief paper involving the Probabilistic Boolean Network modeling of genomic regulation. As a result, Ivanov earned a postdoctoral position in the Training Program in Biostatistics, Bioinformatics, Nutrition, and Cancer led by Dr. Raymond J. Carroll-a distinguished professor in the statistics department at Texas A&M.;
For the next two and a half years, Ivanov began to learn more and more about biology and biological systems. It was during this time he was invited to work on a project with Dr. Robert Chapkin-a distinguished professor in the Department of Nutrition and Food Science. Through that collaborative effort, Ivanov was soon invited to consider a position at the CVM. After giving a talk to the faculty of the interdisciplinary program in toxicology, Ivanov spoke with Dr. Glen Laine, former head of the veterinary physiology and pharmacology department.
“Dr. Laine, who has a background in physics, understood the importance of the mathematics behind my presentation, and he offered me a position,” said Ivanov. “Totally by accident, or by fate, I ended up in the veterinary school, and then things started blossoming. I began collaborating with people from the college and other places. Now, in collaboration with the Fred Hutchinson Cancer Research Center in Seattle, Washington, we are taking part in a human trial about the potential benefit of lignan food supplementation in promoting colon health that may have direct application to cancer prevention. So, by coincidence, all of this is one big circle, supported by the foundation of mathematics.”
From Computers to Cancer
Engineers, according to Ivanov, have long examined mathematical models to help control complex systems like airplanes, cars, and computers. Following in the footsteps of other disciplines such as physics and chemistry, these advances underline the importance of the scientific approach: from experimental design, to developing a predictive mathematical model, validating the model with additional experiments, and ultimately controlling or influencing the system in question.
“It is now time when biology begins to evolve into a mathematically founded discipline,” said Ivanov. “Every time
you investigate areas like molecular biology and cancer, you begin to see complex systems. Gene (dis)regulation, for example, is a current focus in cancer research. In many aspects this process could be modeled after a computer’s architecture and logic. It [gene regulation] is a network. A computer is essentially what is known as a Turing machine, so things that are developed already by mathematicians and engineers-like logical gates and circuits-could be applied directly to biology, especially in cases where complex biological systems are faced with choices, and decisions are made by their regulatory elements.”
From Ivanov’s perspective, without having a systems approach to biology there would be less progress, because scientists would be missing a great part of the picture. Where many would see a wall between the sciences, Ivanov sees opportunity. Mathematical modeling, for him, has gone beyond just a discipline. It is becoming that common foundation, that common language that brings disciplines together. “If we don’t speak a common language, we will never do anything together,” said Ivanov. “Engineers will keep working on circuits and computers, and biologists will just do what Darwin used to do, which is categorizing all the different observed cases and trying to comprehend and explain huge degrees of variation. This is impossible for a human brain to do without a proper foundation.”
From Theory to Application
“The current understanding is that cancer is a molecular disease, which means it’s based on genes and their regulatory interactions within the cell. These genes are not alone, they communicate via different pathways with other genes and external to the cell stimuli,” explained Ivanov. “In this way, they form a communication network. Focusing on an individual gene might not lead to the desired result, because if you hit that gene with a drug, the cancer cell often has the capability to re-route its regulatory activity and still reach a proliferative state that causes the cancer to metastasize.”
“What is needed is to model the entire network or pathway of how the genes are communicating with each other,” said Ivanov. “Using these models, we can predict which genes are ‘turned on’ or highly expressed or ‘turned off’ or down regulated. You have to look beyond just the one gene and target the network if you want to control cancer.”
Ivanov explains that using mathematical models in biology has led to the concept of master-slave gene regulatory networks where one “master” gene controls the activity of a large number of “slave” genes. The thought is that if you can control the masters or some of the intermediate genes, you actually control the entire system. But this can be a tricky and difficult task. “You have to discover them [the master genes], and usually they are well-hidden because they are not usually highly up or down regulated,” said Ivanov. “What is highly up or down regulated are the slave genes, because they are controlled by the masters. You have to figure out which one of the entire section is the master gene and then develop a model-based strategy to control it.”
Ivanov is quick to admit that the potential of this approach is not going to immediately result in a cure for cancer, but it could lead to the ability to control the cancer and stop it from spreading in the body. In addition to his ongoing work in developing mathematical models for cancer biology, Ivanov also continues to collaborate with his colleagues in the food and nutrition sciences department. A recent study that used his mathematical models involved examining the microbiota that naturally live in the digestive tract and how they react with gut epithelial cells. The study found that babies fed a certain type of formula develop genetic signatures similar to babies born prematurely.
“This is an exciting finding and is important because people know if a baby is premature, it has a much higher risk of developing some kind of immunological problem in the future; therefore, babies who are fed that particular type of formula might have that same risk,” said Ivanov. “Babies who are breastfed showed the same kind of gene expression variations we would expect in a normal population.”
The research team determined that such gene expression signatures are strongly related to the composition of the gut microbiome, which suggests that there exists a certain epigenetic “programming” through the interactions of the nutrients, microbiota, and the epithelial cells in the digestive tract.
“These interactions represent a very complex system,” said Ivanov. “We have so many microbes naturally living in our digestive system, and many different cell types. We had to develop a way to model that interaction. That’s very exciting.” Ivanov’s expertise in abstract mathematics and mathematical modeling of complex systems enables him to serve as a bridge among diverse scientific fields. He aids leading edge research by developing theoretical approaches to controlling complex systems, finding applied methods for controlling cancer initiation and progression, and understanding how microbes in the digestive system influence human development from a very early stage of an infant’s life.
Ivanov engages investigators through his work in the Center for Translational Environmental Health Research (CTEHR). The CTEHR, a collaboration among Texas A&M; University, Baylor College of Medicine, and the University of Houston, has a mission to “improve human environmental health by integrating advances in basic, biomedical, and engineering research across translational boundaries from the laboratory to the clinic and to the community and back.” Here, Ivanov directs the CTEHR’s Quantitative Biology Core, which provides investigators with genomic, bioinformatics, and statistical and computational biological support services for their studies. This also includes helping to develop mathematical models.
Mentoring and Modeling
Even though Ivanov has played an integral role in bridging the gap between scientific disciplines, he says his greatest accomplishment is the success of the graduate students he mentors.
“One of my best students, Jason Knight, just successfully defended his doctoral dissertation, and I’m very proud of him,” said Ivanov. “His work was focused on developing modelbased frameworks for classification, finding gene signatures for any kind of condition-not just cancer. In mentoring students like Jason, I can bring in colleagues from many different fields, experts, to create a unique and meaningful graduate experience.”
In addition to his work with colleagues and mentoring graduate students, Ivanov is passionate about his work and the potential it has to impact cancer prevention and treatment, and perhaps other chronic conditions. “I am trying to find ways to reduce the complexity of these mathematical models of gene regulation,” said Ivanov. “We know that we can never model a thirty thousand gene network. It might be possible only with a supercomputer, but even then the computations that predict the dynamic behavior of the system would not be finished until after human beings are long gone. I’m trying to figure out how we can start with a large gene regulatory network model and reduce it to the most important twenty to fifty genes. Of course, we lose information, but maybe the larger regulatory system or a portion of it can still be controlled sufficiently well so that a new drug or other treatment can be developed to control cancer or some other chronic condition. In other words, the goal is to prevent or control a complex disease and keep it from progressing.”
Consequently, Ivanov views his work through the lens of complex systems. When asked the best part of his job, Ivanov replied, “It’s getting my hands on a model and finding a way to simplify it, it’s watching students develop that understanding of the complexity of the world around them, and it’s learning from my colleagues. It’s all of the above. Those things, in a way, form a network that induces my curiosity. I learn from my students and I learn from my colleagues because they have different perspectives. Then I go into my own world and I rethink all of those interactions and what I learn from them. What I take from them shows me how I should proceed. It’s great.”
A disease most people have never heard of, which has come to the Americas only in the last year, may soon become a major public health issue in the United States. Chikungunya (pronunciation: chik-en-gun-ye) virus has been recognized as the cause of periodic epidemics in Africa and Asia since the 1950s and has now spread to all but six countries in the Americas, with over 1.4 million suspected cases since first arriving in the Caribbean in late 2013. There have been 11 cases thus far reported in Florida where the patient had not reported any recent travel.
“We have local transmission in the United States,” said Dr. Rosina “Tammi” Krecek, a visiting professor and interim assistant dean of One Health at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM). “We also have imported transmission. An example of local transmission is ‘I didn’t leave home, a mosquito bit me, and I became infected.’ Imported transmission is ‘I flew to an endemic country, a mosquito bit me, and I became infected and returned with the infection.'”
The virus is spread among humans by the bite of either of two species of mosquitoes: Aedes aegypti (“yellow fever mosquito”) and, less commonly, Aedes albopictus (“tiger mosquito”). When the mosquito bites an infected person and then subsequently bites a healthy individual, the virus can be transferred to that second person. Aedes aegypti can be found in the southeastern United States from Texas to South Carolina, while Aedes albopictus can be found as far north as New York City.
“In some parts of the country, there’s really no risk of initiating transmission, but anywhere in the southeast, there is a risk, especially during the summer,” said Dr. Scott C. Weaver, director of the Institute for Human Infections and Immunity at The University of Texas Medical Branch at Galveston, who collaborates with Krecek and others at Texas A&M on this disease.
One worry the scientists have is that if the virus were to mutate to make it more easily spread by Aedes albopictus mosquitoes, a much larger percentage of the United States population could be affected.
Health officials in the Caribbean are urging businesses and individuals to eliminate standing water and take other precautionary measures against mosquitoes. Unfortunately, these kinds of mosquitoes tend to thrive in urban areas, including inside buildings, so simply fumigating the outside areas with insecticide is unlikely to have much effect. Therefore, travelers must take it upon themselves to exercise reasonable precautions, including wearing mosquito repellent and sleeping in rooms with screened windows, air conditioning, or mosquito netting. As there is no treatment or vaccine for the chikungunya virus, preventing mosquito bites remains the only defense.
Chikungunya virus comprises a clear example of One Health defined as the inextricable link between animal, human, and environmental health. Because animals and the environment are considered important factors in human disease, the best way to combat a virus like chikungunya is a One Health approach. Furthermore, humans are not the only ones who can become infected. “There is some evidence that animals-including non-human primates, small mammals, and birds-may act as reservoirs for the virus,” said Dr. Christine Budke, an associate professor at the CVM. “However, because it’s a new virus to this part of the world, there’s very little information on non-human reservoirs in the Americas.”
“There is a risk that the virus could use non-human reservoirs in South and Central America, where there are plenty of wild primates, but we simply don’t know if those species are competent to serve as reservoir hosts,” Weaver said. “We also don’t know if the mosquitoes that are present in the forest habitats where those monkeys live would be competent to transmit in a monkey/mosquito cycle, like exists in Africa.”
Other factors affecting the transmission of the virus may include movement of people and animals as well as changes in climate, but how that works is also largely unknown. “We don’t fully understand the role of the mosquito or the role of climate in the disease cycle,” Krecek said. “We don’t know how the mosquito is influenced by the environment. For example, what leads to a more, or less hospitable habitat for the vector?”
As of January 1, 2015, chikungunya is a reportable disease, meaning doctors must tell the Centers for Disease Control and Prevention (CDC) of any cases. Although this move demonstrates the CDC’s concern about this virus, experts say it is unlikely to result in increased numbers of cases reported, as doctors already generally report any cases they see of this unusual virus.
An issue is that this disease mimics other, more common diseases. Symptoms typically begin, three to seven days after being bitten by an infected mosquito, with a sudden high fever and joint pain, often followed by headaches, muscle pain, coughing, joint swelling, and/or a rash. Although the disease is rarely life threatening and symptoms subside in many people within a few weeks, for some of those with the disease (estimated at up to 60 percent by some studies), the joint pain may last for months or even years and can be so debilitating they are unable to go about their normal lives.
“I’ve received emails from a lot of people here in the United States who have become infected, travelers mostly,” Weaver said. “They’re a month or two out after their infection, and they’re still experiencing severe arthralgia and asking about experimental treatments, or anything else that they can do. Unfortunately, there’s not much other than our typical non-steroidal anti-inflammatory drugs that you would take for pain and swelling for people with chikungunya.”
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
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
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.”
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.
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.
The 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.
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.
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.”
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.
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.
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. 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.
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.
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.”
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.
A 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.