Dr. Heather Wilson-Robles, an associate professor and the Dr. Fred A. and Vola N. Palmer Chair in Comparative Oncology in the Texas A&M College of Veterinary Medicine & Biomedical Sciences’ (CVM) Small Animal Clinical Sciences Department, has been awarded a $94,255 research grant from the St. Baldrick’s Foundation.
Dr. Heather Wilson-Robles
“Dr. Wilson-Robles is a quintessential clinician-scholar whose independent and collaborative discoveries are carving the path to a better understanding of cancer and, ultimately, to effective cancer treatments in canine patients that will eventually translate to human patients,” said Dr. Eleanor M. Green, the Carl B. King Dean of Veterinary Medicine at Texas A&M University.
Wilson-Robles’ grant is one of 90 given to professors from across the country by St. Baldrick’s Foundation. The foundation is providing $23.5 million in its summer grant cycle to support the brightest minds in the pediatric cancer field.
“For nearly a decade, Dr. Wilson-Robles has conducted leading-edge clinical trials that impact human and animal health,” said Dr. Jonathan Levine, department head, professor, and Helen McWhorter Chair in Small Animal Clinical Sciences. “This grant represents an exciting extension of her work on bone cancer, this time exploring the lethal spread of tumor cells to other sites in the body.”
Her project, funded through June 2018, will examine a new drug that targets the cells that spread; this process has shown promise as a therapy.
“Bone cancer is an aggressive disease in both children and pet dogs that can be painful and often leads to death of the patient even with aggressive surgery and chemotherapy,” Wilson-Robles said. “Most often these patients die because the tumor has spread to other areas of the body, not from the original bone tumor, which is often removed with surgery. Therefore, in order to better battle this disease, new therapies that target the cells that spread are needed.
“Our goal is to more thoroughly investigate this drug for its ability to prevent or delay spread of the tumor cells using both human and dog bone tumor cells,” she said.
Every two minutes a child is diagnosed with cancer worldwide. One in five kids diagnosed in the U.S. will not survive, and of those who do, two-thirds will suffer from long-term effects from the very treatment that saved their life; each phase of the research process, from the laboratory to translational research to clinical trials, plays a crucial part in developing new therapies that will give kids with cancer the healthy childhoods they deserve.
“St. Baldrick’s leads the charge to take childhood back from cancer and is dedicated to funding the best research, no matter where it takes place,” said Kathleen Ruddy, CEO of the St. Baldrick’s Foundation. “Through our grants, we are proud to support world-class experts of today, as well as the next generation of researchers whose innovative approaches employ cutting-edge technology and emerging science to find cures and treatments to create a growing generation of childhood cancer survivors.”
For more than 16 years, researchers and volunteers have been observing wildlife along the clay cliffs of Southeastern Peru’s Tambopata River. They’ve gathered data every day, logging more than 20,000 hours and building one of the most extensive datasets on tropical parrots in the world.
Dr. Donald Brightsmith
In a new paper published in Ibis, Elizabeth Hobson, a postdoctoral fellow with the Arizona State University-Santa Fe Institute Center for Biosocial Complex Systems, and Donald J. Brightsmith, a professor in the Texas A&M University College of Veterinary Medicine & Biomedical Sciences (CVM) and director of the Tambopata Macaw Project, begin to analyze the data from this long-term study.
In particular, the two explore the potential drivers behind geophagy—or intentional soil consumption—they’ve regularly observed in 14 different parrot species there.
This region of the Tambopata River in Southeast Peru is an ideal spot to study the nearly two-dozen parrot species that live nearby in the Amazon rainforest. In the thick foliage of the jungle, the birds are difficult to see, but when they emerge to gather up beakfuls of the sodium-rich clay soil, “it’s a crazy, screaming kaleidoscope of color,” Hobson said.
“They’re all quiet when they take flight, but in a few seconds, they all begin to scream, and some drop bits of the clay from their mouths,” said Brightsmith, who has led the Tambopata Macaw Project since 1999. “It’s an incredible experience.”
But geophagy is a somewhat confounding behavior—clay soil is basically inert.
“It doesn’t have proteins, carbohydrates, or really anything that you’d need,” Brightsmith said. “If we can understand why it’s so important to these parrots, we can learn more about the ecosystem and how it affects the other insects, birds, and mammals who also eat this soil.”
Geophagy occurs around the world and in many types of animals, and scientists have proposed many explanations for the behavior. In their paper, Hobson and Brightsmith explore the two leading theories for these Amazonian parrots—that clay soils help protect the birds from food toxins when ideal food sources are scarce and that clay soils provide necessary minerals not available in the parrots’ regular diet.
Like previous studies, their analysis suggests that toxin-protection is not a driver. But parrot geophagy there is highly correlated with breeding season, suggesting the increased nutritional demands are likely behind the soil consumption. This study also joins a large body of research suggesting that hunger for sodium, specifically, is that driver.
“There’s lots of evidence that’s pointing in that direction,” Hobson said. “Sodium in the rainforest is really rare, and the place on these clay licks most preferred by the birds also has the highest sodium content.”
Understanding how nutritional needs are—and are not—being met during breeding season becomes even more important in light of climate change, according to Brightsmith. Some of the larger macaws are already breeding right before a seasonal crash in food supply, requiring parents take their fledgling young on long flights to find food.
“If climate change starts messing with the macaw’s food supply, it could disrupt their ability to breed,” he said.
A team of scientists including Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM) associate professor of immunology Dr. Michael Criscitiello have achieved a significant step forward in HIV research, eliciting broadly neutralizing antibodies (bNAbs) to the virus by immunizing calves.
Dr. Michael Criscitiello
The National Institutes of Health (NIH)-supported scientists reported the findings in a paper published online July 20 in the academic journal Nature. Those findings offer insights for HIV vaccine design and support further study of modified bovine antibodies as HIV therapeutics or prevention tools in humans.
Researchers have observed that about 10-20 percent of people living with HIV naturally develop neutralizing antibodies to the virus, but usually only after nearly two years of infection. These neutralizing antibodies have been shown in the laboratory to stop most HIV strains from infecting human cells and to protect animal models from infection.
However, scientists have so far been unsuccessful in prompting the human immune system to produce these antibodies through immunization. Further, while bNAbs isolated from people with HIV infection have demonstrated promise in primate studies and have entered human studies for HIV prevention and treatment, questions remain about whether effective antibodies could be produced rapidly and at a scale suitable for widespread distribution.
The researchers have determined that cattle may offer some help in solving these problems.
“This work is exciting because a structural and genetic oddity in cattle antibodies appears to allow them to easily and quickly make effective antibodies to HIV that humans cannot,” Criscitiello said. “The cattle antibodies may themselves be useful—with a few tweaks—in humans.”
While bovine neutralizing antibodies are not likely suitable for clinical use in humans in their current form, exploring this rapid production may help answer important research questions.
“From the early days of the epidemic, we have recognized that HIV is very good at evading immunity, so exceptional immune systems that naturally produce broadly neutralizing antibodies to HIV are of great interest—whether they belong to humans or cattle,” said Dr. Anthony S. Fauci, NIAID director.
“We never dealt with the entire HIV virus here (at Texas A&M), but the cattle received immunizations containing a protein designed to mimic a surface protein on HIV,” said Criscitiello, who coordinated the A&M efforts with Scripps, managed the animal work, and analyzed the antibody immunogenetics.
While no one knows definitively why these powerful antibodies evolved in cattle, one theory holds that the animals’ long HCDR3 loops are tied to their extensive gastrointestinal systems. Cattle and other ruminant animals have multi-chambered stomachs and a robust population of bacteria in their digestive tracts to help break down a diet of tough grasses. However, these bacteria can pose an infection risk if they escape the gut, so cattle with a versatile mechanism for producing potent antibodies would greatly benefit from the increased protection.
“A minority of people living with HIV produce neutralizing antibodies, but only after a significant period of infection, at which point virus in their body has already evolved to resist these defenses,” said Dennis R. Burton, Ph.D., a lead author on the study, director of the NIH’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery and scientific director of the IAVI Neutralizing Antibody Consortium at the Scripps Research Institute. “Unlike human antibodies, cattle antibodies are more likely to bear unique features and gain an edge over complicated HIV immunogens.”
Further study on how this mechanism contributed to the elicitation of bNAbs to HIV in cattle may inspire novel approaches to HIV vaccine development.
“HIV is a human virus,” said Devin Sok, a study leader and IAVI collaborator at the Scripps Research Institute, “but researchers can certainly learn from immune responses across the animal kingdom.”
Researchers may also explore mimicking or modifying the potent isolated bNAb, or those like it, to develop antibody-based HIV therapeutics and prevention tools, as well as treatments for other pathogens that have evolved to avoid human antibody responses. Because the current research indicates that the bovine immune system may typically work quickly to produce effective antibodies against difficult pathogens such as HIV, immunizing cattle and discovering such antibodies may become a useful approach to ensure these tools are readily accessible.
Discovery and the unexpected—these are recurring themes in the research career of Dr. Stephen Safe, a distinguished professor at the College of Veterinary Medicine & Biomedical Sciences (CVM). Trained as a chemist, Safe eventually found himself studying toxicology and examining the biochemical mechanisms of cancer with the hopes of developing effective drug treatments.
Dr. Stephen Safe
Safe looks at receptors, a molecular lock to which chemical signals are the keys. When these chemical signals bind to the receptor, or turn the metaphorical key, it leads to a Rube Goldberg–like process, where one action affects another and then another, ultimately powering various biological processes.
“Receptors are needed for life,” Safe said. “They are sensing molecules. They sense light. For example, you need sunlight to produce Vitamin D. What does Vitamin D do? It would do nothing if there wasn’t a Vitamin D receptor.”
And, it all started with a single receptor—the aryl hydrocarbon, or AH, receptor. Known to play a role in a chemical’s toxicity in the body, the AH receptor was not known for its health benefits. However, research trends led Safe and his colleagues to suspect that this receptor’s function was far from black and white. There were, in fact, health benefits yet to be uncovered.
“I started off working on toxic compounds that bound to the AH receptor. It was always thought to be a receptor that was important for driving toxicity of various chemicals that bound to it,” Safe said. “Many people have discovered in the last 20 years that this receptor plays a huge role in all sorts of things, including the health of your gut, the health of your skin, and autoimmune diseases. We’ve been looking at ligands—or compounds that bind this receptor—that aren’t toxic. We’re using them for treating cancers, and investigating the heath benefits of the receptors in gut microbiota.”
Excited by the possible health benefits associated with the AH receptor, Safe began looking for practical solutions to ailments such as pancreatic cancer. Through partnerships with pharmaceutical companies, Safe is working toward developing effective drug treatments that would specifically focus on receptors like the AH and NR4A1 receptors to promote pathways that prevent cancer growth. “We’ve got a new group of drugs that look like they’re really going to knock your socks off,” Safe said.
Dr. Safe with his research team in the laboratory
Safe’s interest in the AH receptor has stimulated an interest in other receptors, such as NR4A1, which Safe and his colleagues are investigating for the treatment of multiple cancers including rhabdomyosarcoma—a devastating children’s cancer. “We think the AH and NR4A1 receptors are really important in cancer, and we’ve been developing drugs that target them through different pathways,” he said.
Developing these drugs can be a balancing act, looking for the appropriate dose to ensure effectiveness. “We’re trying to develop drugs that we can give at a much lower concentration to hopefully be below the toxic threshold. We think that they have relatively low toxicity and expect that the side effects will be minimal. In addition, they’re also useful for combination therapies.”
Safe’s fascination with the AH receptor has caused his research to take an unexpected turn. In collaboration with other researchers at Texas A&M, he is focusing on the effects of microbial and food-derived AH-receptor compounds on gut health. For example, eating cruciferous vegetables, such as cabbage, could provide similar effects as the compounds acting on the AH receptor. “Maybe plants that produce a lot of AH receptor compounds, like cruciferous vegetables, which are known to be health-protective, could be combined with what the microbiota produces. The two in combination could be dynamite,” he said.
The twists and turns of Safe’s research has led to continuous learning and a deep curiosity. “The good thing for me is I started off as a chemist and all we do in my lab is oncology and molecular biology. So, I’m learning all the time,” he said. Beyond the AH receptor discovery, Safe continues to search for much needed practical, life-saving therapies.
Dr. Noah Cohen, professor and associate department head for research and graduate studies in the Department of Large Animal Clinical Sciences at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), is leading the search for an effective strategy to prevent diseases caused by Rhodococcus
equi (R. equi), a bacterium that commonly causes diseases in foals and in humans and animals with suppressed immune systems.
Dr. Noah Cohen
R. equi may not always cause disease in an infected animal, but when it does, pneumonia is most often the disease that develops. R. equi frequently infects the lungs of foals, causing severe symptoms, such as fever and coughing, which can potentially lead to death. In addition to disease in the lungs, R. equi can affect bones, kidneys, the intestinal tract, and other parts of the body.
To combat this potentially deadly pathogen, clinician-scientists like Cohen are working to develop strategies other than antibiotics that stimulate the patient’s immune system to help protect them from infection.
Coming to the CVM
In 1988, Cohen came to the CVM as an assistant professor in veterinary public health. However, his interest in applying epidemiology to large animal medicine soon led him to a residency in large animal internal medicine at the CVM. “I was honored and excited about my residency,” he said. “There were outstanding equine internists at Texas A&M, including Drs. Kent Carter, Joe Joyce, Tom Kasari, Bill McMullen, Dub Ruoff, and Allen Roussel. I knew that the excellent clinical training would enable me to identify critical questions for research. The opportunities and clinical questions seemed endless.”
Before he started his residency, Cohen had the opportunity to meet Dr. Ronald J. Martens, the department head of what is now the Department of Large Animal Clinical Sciences. Several years before Cohen came to the CVM, Martens founded the Texas A&M Equine Infectious Disease Laboratory (EIDL) to combat infectious diseases such as those caused by R. equi. Martens’ work in infectious diseases as a clinician-scientist inspired Cohen to complete his residency and join the faculty of the CVM.
“Dr. Martens had the vision to recognize that a clinician-scientist with an interest in epidemiology would be of benefit to the department,” Cohen explained. “He encouraged me to complete my residency training in internal medicine, and then he recruited me to become a member of the large animal medicine faculty.”
After he completed his residency, Cohen began researching R.equi in the EIDL under the direction of Martens. The main goal of Martens’ research was to find an effective preventative measure against infections caused by R. equi in foals because none previously existed.
Treating pneumonia caused by R. equi can be difficult because treatment is lengthy, expensive, must be administered multiple times daily, can cause serious side-effects, and isn’t always effective. This is why Martens began working on ways to decrease foals’ susceptibility to developing disease from the bacteria.
On breeding farms, pneumonia caused by R. equi is the most common and severe form of pneumonia in foals that are between the ages of one and six months. Pneumonia is a leading cause of disease and death for foals, which has motivated researchers like Martens and Cohen to seek an effective preventative strategy against pneumonia caused by R. equi. A vaccine to directly prevent the disease would be a major breakthrough for the health of foals on breeding farms, according to Cohen.
Martens recognized the prevalence of R. equi in foals and knew the importance of preventing R. equi–related diseases, especially pneumonia. Martens’ biggest contribution to the prevention of R. equi disease was the use of hyperimmune plasma, which is harvested from the blood of horses that were vaccinated to produce high concentrations of antibodies againstR. equi. The plasma is then transfused to foals. These transfusions partially protect foals against infection with R.equi.
“The collection and transfusion of plasma that is hyperimmune against R. equi remains the only acceptable and commercially available approach for preventing R. equi pneumonia,” Cohen said. “Unfortunately, it is not completely effective and has some other limitations, such as being expensive, labor-intensive to administer, and carrying some health risks for foals. Although the concept of preventing the disease by administering antibiotics has been demonstrated to be effective, this approach isn’t acceptable because it isn’t uniformly effective and, most importantly, can contribute to antibiotic resistance from overuse.”
Martens was also interested in identifying alternatives to traditional antibiotics to control R. equi pneumonia because of emerging resistance to drugs commonly used to treat the disease. When Martens retired, he passed on the directorship of the EIDL to Cohen.
Dr. Cohen and students work with an equine patient.
Exploring alternative treatments of R. equi pneumonia as opposed to traditional antimicrobial drugs remains an area of interest for the EIDL. “We are working on two strategies for preventing R. equi pneumonia based on having the patient’s immune system protect them from infection rather than antibiotics,” Cohen said. “First, we are working on developing a vaccine, which is a traditional and effective approach for preventing infections. Second, in collaboration with investigators from the Texas A&M University System’s Institute for Biosciences and Technology (IBT) in Houston, we are investigating if a mist inhaled into the lungs can stimulate a foal’s immune system to protect it against R.
equi infection.”
Collaboration
The CVM’s collaboration with numerous researchers worldwide is a critical component of Cohen’s goal to prevent R. equi pneumonia in foals. Cohen has collaborators in Brazil, Canada, Germany, Japan, and other countries, all of whom have contributed to the growing research in R. equi pneumonia prevention.
In addition, Cohen said his research project benefits significantly from many researchers in the United States and the CVM. “We collaborate with numerous investigators from many countries,” he explained. “We work especially close with Dr. Steeve Giguère from the University of Georgia, one of the world’s authorities on this disease. We are also fortunate to benefit from many scientists at the CVM.”
Results
To reduce the risk of antibiotic resistance, Cohen and his team are investigating new drugs and potential methods of administering preventative and therapeutic agents. After over five years of trying, Cohen and his team at the CVM have produced encouraging results with a vaccine for R. equi pneumonia.
“We are exploring new approaches that we hope will be effective and not promote antibiotic resistance in R. equi,” Cohen said. “Examples include using inhaled substances that facilitate the foal’s own immune system by stimulating receptors of the immune system that eliminate R. equi, and drugs such as metal-based compounds and antibiotics that will reduce the risk of resistance.”
One Health
The strategies Cohen and his team are exploring may have positive implications for other animals, including humans. Since there are striking similarities between R. equi and Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB), their research on R. equi may give rise to potential therapies or preventives against TB in humans.
“Our vaccine research on R. equi might be an appropriate strategy for preventing TB, which would be of global importance for human health,” Cohen explained. “Additionally, the strategy developed by Dr. Gerald Pier and his colleagues at the Harvard Medical School, with whom we collaborate, is innovative and could lead to a ‘broad-spectrum’ vaccine that is effective against many infectious agents.”
The One Health Initiative, which stresses the connection between animal health, human health, and the environment, is an integral part of Cohen’s research. “Although our hearts and minds are committed to improving equine health, we are very much engaged in the One Health Initiative with our activities,” he said. “Developing new types of antibiotics and vaccines that can reduce the need for antibiotics is important for equine and human health because bacterial diseases remain important causes of disease for all species, and the emergence of antimicrobial resistance is a global health crisis in veterinary and human medicine.”
Research Support
As Cohen continues his research on R. equi, he links his accomplishments and new findings to the support that Martens provided him when he began his journey at the CVM. Martens was more than an administrator or a clinician-scientist for Cohen to look up to; he was a mentor.
“I learned so much from him, and we worked synergistically,” Cohen said. “One of the most important things I learned from Dr. Martens was that research is always better when done as a team. Martens was a role model for leadership, and he helped create a work environment in which we could work passionately, assiduously, and enjoyably. He offered advice and humor that made it fun to come to work each day.” In addition, Cohen expressed his gratitude for the cooperation and support from everyone at the CVM because it has positively impacted the success of his research.
Before retirement from the CVM, Cohen hopes to develop a vaccine to control R. equi pneumonia because “it is of global importance.” He would like to help shift the emphasis of treating infectious bacterial disease with antibiotics to methods that help the patient’s immune response protect them against infection. This is of utmost importance because bacteria are rapidly developing resistance to antibiotic treatment.
Cohen also recognizes the significance of students, believing they are the leaders of tomorrow. He aspires to make a positive impact on students by encouraging their research efforts. “During my time at the CVM, I would like to have trained scientists, including veterinary clinician-scientists, whose future contributions will far surpass mine,” he said.
More About Dr. Noah Cohen
Cohen’s interest in veterinary epidemiology and large animal internal medicine led him to the CVM, where he began researching R. equi in the late 1980s; however, his passion for epidemiology developed during his childhood.
“I was born in Pennsylvania, but I spent my middle school and high school years in Switzerland and Israel because of my father’s work,” Cohen said. “My father was a veterinarian who was interested in zoonotic diseases, and this strongly influenced my career. He worked for many years at the University of Pennsylvania’s School of Veterinary Medicine. I spent a lot of time at the Bolton Center, the university’s large animal hospital, where I fell in love with the idea of being an equine veterinarian.”
Cohen attended the University of Pennsylvania where he earned his undergraduate degree in oriental studies with a minor in biology and his VMD (Veterinariae Medicinae Doctoris). After he earned his VMD, Cohen spent over two years in private equine practice in and around Toronto and Ontario, Canada. He then earned his MPH and Ph.D. in epidemiology from the Johns Hopkins University School of Hygiene and Public Health, now known as the Bloomberg School of Public Health.
“At Penn, I benefitted greatly from a liberal arts education and the challenge to think and work independently,” Cohen explained. “In veterinary school, I had teachers whose expertise and dedication to excellence inspired my career. At Johns Hopkins, I was exposed to clinical and research excellence, and the principle that optimal clinical medicine and biomedical research are inextricably linked.”
Cohen continued, “I was trained by superb clinicians and fellow residents in the art and science of clinical medicine at Texas A&M. I also learned about the extraordinary commitment that clinical faculty have for teaching veterinary students. My mentors at Texas A&M instilled in me the ‘students first’ attitude that is a cornerstone of Aggie education. I cherish each of these three institutions for enabling me to do what I love: to teach, to learn, and to help others reach their goals.”
Texas A&M University and University of Texas at Austin researchers have discovered that in dogs with naturally occurring spinal cord injury, a drug that blocks matrix metalloproteinases (MMPs) allows the bladder to stretch more easily as it fills. Such a change will likely reduce the discomfort that is commonly associated with the inability to void urine after spinal cord injury and may improve bladder function.
This clinical trial, evaluated 93 dogs that sustained naturally occurring spinal cord injuries resulting from disc herniation. These injuries are most common in dachshunds, a breed that has a 20 percent lifetime risk of developing disc herniation, which can often cause sudden spinal cord injuries, according to Dr. Jonathan Levine, a professor of neurology and neurosurgery and department head of Small Animal Clinical Sciences in Texas A&M’s College of Veterinary Medicine & Biomedical Sciences (CVM).
“This breed has degeneration of their discs, including changes like dehydration and mineralization, starting early in life,” Levine said. “Because they have this early onset degeneration, dachshunds are set up to have disc herniation at a higher rate than other breeds.
“For a dachshund, these disc herniations consist of rapid displacement of the disc and bruising plus compression of the spinal cord,” he said.
This clinical trial, funded by the U.S. Department of Defense and published in the 2017 May issue of the Journal of Neurotrauma, was based upon earlier studies led by Linda Noble-Hauesslein at the University of Texas at Austin, in collaboration with colleagues at the University of California at San Francisco. Those early study were the first to demonstrate that MMPs, present in the injured spinal cord, contributed to the long-term loss of function after spinal cord injury. These encouraging findings led to the two-cohort clinical trial in spinal cord injured dogs in which Levine and his team administered the MMP inhibitor GM6001 to one set of dogs and provided a placebo to another set.
It is often difficult to empty the bladder after spinal cord injury and this can result in an increase in pressure within the organ. Using a technique called cystometry, the researchers measured the pressure in the bladder and found that dogs treated with GM6001 showed a greater capacity to stretch in response to filling (called compliance).
“We were trying to figure out how they recover from a urinary standpoint. Nobody knew. We knew a little bit just observing the dogs, whether they urinated again or not after their injuries,” Levine said. “What we found was that dogs that got the drug had bladders that were a little more forgiving, or a little more stretchy, compared to dogs that didn’t.”
The results, according to Levine, have significant implications for humans with spinal cord injuries as well.
“These injuries are actually very similar to traumatic spinal cord injuries in people, where there is compression and bruising of the cord,” he said. “People with injuries often have bladders that don’t stretch very well, so they might fill just a small amount of urine and then they have to empty. They have bladder urgency; it’s very uncomfortable.
“If you talk to people with spinal cord injury or you look at the literature, what you learn is that recovery of urinary function is as important or more important to those individuals than walking,” he said.
As many as 12,000 people in the United States are affected by acute spinal cord injuries similar to those found in dachshunds, and while there is a movement within the drug industry to use therapies already approved by the FDA, Levine said there are classes of FDA-approved drugs that are very similar to GM6001 that are currently being used for different treatments but, with further study, might be applicable to human spinal cord injuries as well.
“The results of this study are really encouraging in terms of a way forward,” Levine said. “There’s a lot of additional information that needs to get uncovered, but this is a first and very intriguing step at looking at how we can help people and dogs that have these injuries.”
Jessica Israel, a graduate student pursuing a non-thesis master’s in biomedical sciences at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), is trekking her own path to a veterinary medicine degree by first immersing herself in research, an unconventional path for most non-thesis graduate students. Through her research experience, she hopes to contribute a different perspective to veterinary medicine. As a member of the deaf community, she will add to the diversity of the veterinary community.
Wendy McNair (interpreter), Jessica Israel, Dr. Cristine Heaps, Amanda Rose (interpreter)
Although some may consider her deafness a challenge, Israel has not let it get in the way of her research. In April 2016, Israel was selected to present her research at the Experimental Biology Conference in San Diego—a conference that presents novel research discoveries in the fields of anatomy, biochemistry and molecular biology, investigative pathology, nutrition, pharmacology, and physiology. Israel’s selection to present at the conference was in recognition for her research and her position as a non-thesis major involved in research.
At the conference, Israel worked alongside interpreters to present her work to fellow scientists. “I had the chance to present my poster to scientists, who listened with interest and wanted to compare and discuss data from their research,” she said. “Scientists with years of experience in their field gave me feedback on how I could improve my experiments. I found this experience stimulating, and it boosted my confidence. The chance to interact with others, network, and listen to what others had to say was an amazing experience.”
There was much preparation for the poster presentation, Israel explained, “the conference provided me with two interpreters who would act as my voice during the duration of the presentation, and I was hesitant to put my trust in those interpreters because I didn’t know if they had a scientific background until I met them. So, I prepared a script with exact wording I would say during the presentation and tried to help them understand what the research project was about prior to giving the presentation. In the morning, I spent four hours practicing my presentation with them, and it took a while for them to learn. In the end, the presentation turned out great.”
The conference also introduced Israel to several scientists who were interested in collaborating with her. This was an opportunity Israel was grateful for. “I would encourage everyone to have a similar experience because it helps develop better interpersonal skills and increase networking,” she said. “I met several people who I would like to stay in touch with and could help me grow professionally.”
Israel’s interests in biomedical sciences and veterinary medicine include small animal surgery and research that could help build an even stronger bridge between human and animal health. Under the direction of Dr. Cristine L. Heaps, an assistant professor in the Department of Veterinary Physiology & Pharmacology at the CVM, Israel conducts research on the circulatory system, something she may continue to focus on after acquiring her master’s degree.
“I haven’t decided specifically which area of focus I want to study in veterinary school, but knowledge of the circulatory system would be beneficial,” Israel said. “I do know I want to focus on the surgical aspect of veterinary medicine and do more extensive surgery.”
Using pigs as models, Israel’s research focuses on endothelial nitric oxide synthase—or eNOS—distribution along the blood vessels that supply the heart and how this can affect blood pressure regulation. These eNOS receptors—which are released by the heart in reaction to stress—aid in the dilation of blood vessels and help regulate blood pressure. The potential to help better understand the role of blood pressure regulation in heart disease attracted Israel to study the cardiovascular system.
“I used to work in a different lab last year under Dr. Thomas Ficht, whose research focus is on brucellosis—an infection spread from animals to people through unpasteurized dairy products,” Israel said. “After working for him for a year, my interest of working in a different lab was piqued by my advisor, Dr. Heaps, who enthusiastically discussed her lab with me. I became curious and thought working in her lab would be fun, especially after being asked the question, ‘Have you ever seen a pig run on a treadmill?’ It was something I have never envisioned, and I was hooked. I asked her if I could work in her lab this year, and she agreed. I managed to see several pigs running on a treadmill; it was a funny and awesome sight.”
Jessica Israel at the Experimental Biology Conference in San Diego
Before Israel was inspired to pursue her education at the CVM, she earned her undergraduate degree in biology and a minor in chemistry at Gallaudet University in Washington D.C., a university for the deaf. Growing up in a deaf community, she attended a deaf school from elementary through high school. The shift to a university full of hearing people for her master’s degree was a challenge. However, Israel quickly adapted to the change.
“It was a huge change for me, using interpreters and other modes of communication besides sign language,” Israel said. “In itself, it was and still is a challenge and great experience.”
Her transition from being immersed within a deaf community to attending Texas A&M University helped prepare Israel for the beginning of her journey toward applying for veterinary school at Texas A&M. Since then, Israel has made Texas A&M her home and is not afraid to push past her obstacles. Her mentors have helped Israel explore her interests and fulfill her goals as a future veterinary student. Israel said she feels the opportunities at Texas A&M are limitless.
“Texas A&M has accommodated my needs and the professors here do a lot to give me the best access to information,” she said. “Several professors were willing to learn sign language in order to communicate with me better. They went beyond my expectations and I am grateful for this.”
Israel’s independent and confident attitude has helped her succeed at the CVM. Her devotion to her research has opened many doors to future collaborations with other scientists, as well as future opportunities to strengthen the connection between human and animal health. Israel is admired by other students and CVM staff and faculty alike.
“I am thoroughly impressed with Jessica’s tenacity as she navigates her way through the curriculum for the non-thesis master’s degree,” Heaps said. “She has performed superbly despite the obstacles to learning that she has had to overcome. In addition to her persistence in the classroom, Jessica has gone beyond that required in the non-thesis master’s program and has spent considerable time in the laboratory and preparing her scientific poster for presentation in San Diego. Jess maintains an incredibly positive attitude while negotiating every hurdle. She is a role model for all students, regardless of whether they are members of the deaf or hearing communities.”
“I am here to educate about deaf culture and show that anyone can do anything,” Israel said. “Members of the deaf community can do as much as anyone else, and I am an example of that.”
Scarlet macaws use an artificial nest box designed by the research team. (Credit: Liz Villanueva Paipay)
Deep in the Peruvian rainforest, 20 kilometers from the nearest road, stands the headquarters of the Tambopata Macaw Project, a combination ecotourism lodge and scientific research station. Waking up well before sunrise, teams of dedicated parrot researchers make daily trips into the jungle, braving intense humidity, thick forests, and unpredictable rivers to observe macaws in their native habitat. They climb up 150-foot trees; spend hours counting birds at clay licks; and carefully gather, measure, and return chicks to nests—while keeping a close eye on the birds’ movements through the rainforest canopy.
These adventures are all in a day’s work at the Tambopata Macaw Project, where an ever-changing crew of scientists, graduate students, foreign volunteers, and Peruvian employees work under the leadership of Dr. Donald Brightsmith, assistant professor in the Department of Veterinary Pathobiology at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM).
Since Brightsmith took over as director in 1999, the group has collected years of data on macaws. “I’ve had researchers recording data every single day since November 2000,” he said. It’s a treasure trove of research that Brightsmith hopes will fill in the knowledge gaps about macaw conservation and ecology.
From Long Island to the Amazon
The Brightsmith family (Gaby, Mandy Lu, and Don) celebrate Christmas 2014 at Tambopata. (Credit: Tambopata Macaw Project)
Brightsmith grew up on Long Island, New York, just outside New York City. Despite his urban roots, he has been a lifelong naturalist and bird watcher, “much to the joy of my classmates, who would pick on me for it all the way through graduate school,” he observed humorously. That early love of birds propelled him through academia, from his bachelor’s degree in natural resources at Cornell University, to his master’s degree in wildlife ecology at the University of Arizona, to his doctorate in zoology at Duke University.
During these years, Brightsmith’s passion for birds focused on a growing interest in parrots. A trip to Costa Rica in graduate school sparked his fascination with tropical birds, and his first wife introduced him “to the world of crazy parrot owners,” he said. But Brightsmith credits a single book—Beissinger and Snyder’s New World Parrots in Crisis (1992)—for opening his eyes to the plight of tropical parrots. “It pointed out that we don’t know much about parrots in the wild,” he said. “They’re having serious problems. They’re highly valuable both as a tourism resource and a captive resource. Yet, especially in the early ’90s, we knew almost nothing about where parrots breed, what they eat, or what habitats they use in the wild. It was an incredible disconnect.”
Around the time he was finishing up his doctoral research in zoology at Duke, Brightsmith was introduced to the Tambopata Macaw Project. Established in 1989, the project had briefly earned international recognition for its work on parrot clay licks and macaw nesting, but since the early 1990s had been languishing. Brightsmith said he saw a golden opportunity to revitalize the project and “make a difference by looking at this group of birds that are hard to work with.” In 1998, he flew to Peru and met with the project leaders. “I convinced them that if they gave me a small amount of money, I wouldn’t be a full-time employee, but I would start to run this research as a scientific endeavor again,” Brightsmith said. His pitch was successful, and the Tambopata Macaw Project was reborn under his enthusiastic leadership.
A marriage of ecotourism and research
The project began in 1989 when Peruvian researchers and entrepreneurs, Eduardo Nycander and Kurt Holle, founded both Rainforest Expeditions, a for-profit ecotourism company, and the Tambopata Macaw Project. From the beginning, Rainforest Expeditions owned and operated the remote lodge that served as both a research base and a tourist destination. “From the beginning, it was always a mixture of tourism and research,” Brightsmith explained. “They wanted the two to feed off of each other.”
So far, the venture has been uniquely successful and financially sustainable. Rainforest Expeditions provides lodging, food, and utilities, charging the macaw researchers a reduced fee. Foreign volunteers pay higher daily fees, and the difference goes toward paying wages and lodging for Peruvian workers. In exchange, every group of tourists at the ecolodge receives a scientific presentation from the researchers about current research and threats to macaws.
The marriage of ecotourism and conservation research is not only a boost to the Peruvian economy, but also one of the main reasons the Tambopata Macaw Project has been able to carry on so successfully for decades. Brightsmith estimated that Rainforest Expeditions provides over $30,000 in project funding every year. “It’s not a completely sustainable system right now, but all it requires is a few thousand dollars of extra financing, which is much cheaper than a full research lab,” Brightsmith said. “This is one of the reasons why the project is still going after 20 years.”
The Schubot connection
Of course, the data they collect still requires a laboratory and experts to analyze it. That’s where Texas A&M’s Schubot Exotic Bird Health Center comes into play. Brightsmith was recruited to Texas A&M by Schubot Center Director and Distinguished Professor Dr. Ian Tizard in 2005. After some initial research collaborations with Brightsmith, Tizard visited the Tambopata Center and offered Brightsmith a job as a lecturer at the CVM.
For Brightsmith, the Schubot Center was an irresistible draw, and the relationship has paid off. “The Schubot Center provides the platform for my work,” he said. “Over the years, they have provided financial assistance and a community of scholars. Because the center exists and it’s endowed, it will always attract a group of people interested in bird research, even those who don’t know that they’re interested in bird research.”
Brightsmith credits Tizard with making the Schubot Center a vibrant hub for avian research, always bringing new scientists from different disciplines into the fold. “If he needs a microbiologist, he finds a microbiologist who knows what a bird is,” Brightsmith said. “Right now we’re working with a geneticist who works on conifer trees, but all of these people are now working on bird-related issues because the Schubot Exotic Bird Health Center exists. I am within that milieu, and it provides a community of people interested in exotic bird issues.”
Current research
Groundbreaking studies about macaws using clay licks to gather essential minerals put Tambopata on the map in the 1990s, and that research continues today. Brightsmith’s team has also published papers explaining their success using artificial nest boxes to increase breeding success. However, over time, the Tambopata project’s main focuses have shifted to new questions.
A scarlet macaw is weighed in February 2016. (Credit: Liz Villanueva Paipay)
Right now, Brightsmith’s main interest is the macaws’ movements and how they change in relation to seasonal events. Researchers use lightweight collars to track the movements of individual birds. Brightsmith said he is concerned about the macaws’ most recent breeding season, which was off to a late and slow start. He speculates that the El Niño weather patterns and the resulting low food supply might have something to do with it. To sort out the irregularities and what they might mean for the future of the species, he hopes to compare data from the past several years.
“At this point, we’ll be able to reflect back and see what happens when you have this odd change in plant resources and how that impacts [macaw movements and breeding],” explained Brightsmith. “Understanding what happens in an El Niño year may give us a better view into the future of what happens as larger-scale climate change alters the plants and their fruiting and flowering.”
Similarly, a shift in movement from one clay lick to another has piqued Brightsmith’s curiosity about the future. “We don’t understand how climate change and clay lick use are rippling through the environment and changing things. We need to look more carefully at these climate-related issues—the annual variations and how they correlate with the environment—which will give us a better ability to predict global change ideas.”
Brightsmith’s wife, Gabriela Vigo Trauco, Peruvian ecologist, Tambopata project coordinator, and current Ph.D. student in Wildlife and Fisheries Sciences at Texas A&M, is “studying scarlet macaw breeding systems using a combination of ecology, animal behavior, and genetic analysis.” The Tambopata location is perfect for her research because that species is not yet endangered in the Peruvian Amazon. “There we can study things that you cannot study in areas in which the species is endangered,” Vigo Trauco explained. “So, that’s the way I want to lead my research.”
CVM students are also using Tambopata as a site for fieldwork and graduate research. Every year, Brightsmith and Dr. Sharman Hoppes, clinical associate professor at the CVM, take two to four veterinary students on a study abroad experience at the station. Students from around Texas A&M’s campus spend time in Tambopata as both volunteers and doctoral researchers.
Hope for the future
Gaby Vigo Trauco shows daughter Mandy Lu how to handle a macaw chick. (Credit: Liz Villanueva Paipay)
These days, Brightsmith and Vigo Trauco make it to Tambopata only twice a year. It’s not as much as they’d like, but their life in College Station keeps them busy. Brightsmith is a full-time assistant professor and admits that he spends most of his time behind a computer, analyzing and writing up data collected from years of research. “Right now, if you told me I could never take another data point on a macaw, I probably could finish out my career publishing on the amount of information we have,” he joked. “We’re currently publishing some of the important relationships between breeding and clay lick use and food and movement. It’s building a jigsaw puzzle where the first thing you have to do is build each piece. We’re building the pieces and fitting them together as we go.”
Vigo Trauco is immersed in reviewing video data from macaw nests. “We have collected over 30,000 hours of video in the past six years,” she said. Additionally, she is restarting her genetic research; a 10-year ban on exporting genetic materials out of Peru was lifted this year, allowing her to move forward with her projects.
Most of all, the couple is devoted to raising their daughter, four-year-old Amanda Lucille, or “Mandy Lu.” For the Brightsmith family, the Tambopata Macaw Project is now a family affair. Brightsmith and Vigo Trauco met on the project, and now they bring their daughter to share in their love of the rainforest and its vibrant inhabitants. Mandy Lu—”our little rainforest monster,” as Brightsmith affectionately calls her—seems to share her parents’ enthusiasm for the Amazon. “Maybe it’s because we like it, and she sees that we’re super happy in the rainforest,” Vigo Trauco speculated. “Maybe she is connecting happiness with being in the jungle.”
Either way, sharing her beloved rainforest with Mandy Lu has shifted Vigo Trauco’s long-term goals for the Tambopata Macaw Project. She envisions the Tambopata project as an opportunity to get Peruvian students interested and involved in conserving their country’s unique natural resources. “I think it would be nice to involve young people—young adults, in high school or their first years of college—and try to put that seed in their brains that conservation can actually help and actually can happen and be fun,” she said.
Brightsmith is also enthusiastic about the opportunities to teach conservation values to people in Peru and around the world. “We’ve had thousands of tourists who have gone through our talks and seen the site and the birds and really gotten a feel for what the real rainforest is like,” he said. He’s also seen changes in local attitudes. “The project has played into this shift in mindset,” he explained. “While some locals use the money they make from ecotourism to buy bigger chainsaws, there is the development of a mindset that has led this community to be much more deliberate in their planning as to how they’re going to use their natural resources.” Both Brightsmith and Vigo Trauco look to the younger generation of Peruvians and conservationists—hopefully some from the CVM—to build a brighter future for macaws and the rainforest.
If you want to visit the site as a tourist or guest, check out
Rainforest Expeditions at www.perunature.com.
Dr. Sharman Hoppes: Avian Veterinarian in the Jungle
Dr. Sharman and her husband, Dr. Bruce Nixon
Since teaming up with Brightsmith in 2008, Sharman Hoppes, DVM, ABVP, and clinical associate professor at the CVM, has been flying south for the winter, straight to the Tambopata Macaw Project.
For two to three weeks, Hoppes trades in her exotic animal clinical duties at the Small Animal Hospital for a small, rustic Amazonian research facility with minimal electricity and no air conditioning. There, she runs the veterinary side of the operation, training students and making sure everybody’s projects stay on track.
Hoppes’ main concern is animal welfare. Working with wild birds unused to human handling adds a layer of complexity to her research. “I’m always very aware that we don’t want to over-stress a bird that we are handling, making it weak or tired and making it a greater risk from predators,” she explained.
Most of the work they do is with the chicks, taking them out of the nest for measurements and sampling. Hoppes states that “they become more used to the handling over time, but even with the chicks, you have to be prepared and monitor how long you have them out.”
When they are trapping adult birds, Hoppes trains her team to work with assembly-line efficiency. Her goal is to minimize contact with the birds, aiming for 10–11 minutes from capture to release. Her team practices their roles in advance using bundled-up towels. “The most important thing is that we’re really prepared and make sure that we have everything within hand’s reach, everything ready to go,” Hoppes said. “Everybody knows their part, and we all know that when we get to this time period, even if we’re not done, we let the bird go.”
Veterinary work in a hot, humid jungle can be challenging, but this self-professed “city girl” revels in it. “This project changed my life,” she said. “I love it there!”
COLLEGE STATION, TX- A study published in PNAS, led by Leif Andersson, professor at Uppsala University, the Swedish University of Agricultural Sciences, and Texas A&M; University, has significant implications for how climate change may affect the reproduction of herring and other marine fishes.
Dr. Leif Andersson
Scientists in Sweden and Canada have studied the genetic basis of reproduction in 25 populations of herring from both sides of the North Atlantic. They revealed that a number of genes associated with the timing of reproduction, and the genetic variants associated with spring or autumn spawning, were found to be largely shared between geographically distant populations.
“We now have a long list of genes associated with timing of reproduction in the herring, and there are some that appear particularly important,” said Andersson. “Animals need to breed at the time of year when their progeny have the best chance of survival.”
The Atlantic herring is one of the most abundant fish in the world and has been a crucial food resource in Northern Europe. The fish spawn in the spring, summer, or autumn; which strategy is the most successful varies from year to year and over time periods due to climate conditions that affect plankton production. It has already been observed in some birds that there is a mismatch between their reproduction and the peak of insect abundance due to a warmer climate (earlier spring).
“This new study has given several interesting results. Firstly, we have revealed that herring populations across the entire Atlantic Ocean are remarkably similar genetically, suggesting that there is gene flow between herring populations. Despite this, we identified clear genetic differences between spring and autumn spawning populations. Furthermore, the genetic factors associated with spawning time were to a large extent shared between geographically distant populations,” explained Sangeet Lamichhaney, former PhD student at Uppsala University and shared first author on the paper.
“One of the most interesting genes is TSHR (thyroid- stimulating hormone receptor) because previous studies in birds and mammals have indicated that this gene has a key role in how animals time their reproduction in response to changes in day length,” Andersson said. “The fact that TSHR was the gene that showed the most consistent association with spawning time in the herring suggests that it has a similar role in fish.
“An important topic for future research is to reveal the molecular mechanism of how increasing day length leads to the initiation of spawning in spring spawners, whereas this response is delayed until August or September for autumn spawners,” he said.
Atlantic herring Photo by Per Eide from the film The Silver of the Sea by blaastfilm.no
“We think that the Atlantic herring has a capacity to respond well to at least moderate changes in the climate,” said Angela Fuentes-Pardo, a Dalhousie University, Canada, PhD student and shared first author on the paper. “Firstly, spawning time is not strictly genetically determined. Herring show some plasticity and adjust spawning time according to the water temperature.
“Secondly, our data suggest that there is a considerable amount of genetic variation affecting spawning time so the herring should be able to adapt genetically to moderate climate changes,” said Fuentes-Pardo.
The study also has important implications for fishery management of the Atlantic herring.
“By providing genetic markers that distinguish spring and autumn spawning herring outside the breeding season, a more sustainable fishery can be developed by optimising fishing among stocks according to their abundance,” said Dalhousie University professor Daniel Ruzzante, who is one of the senior authors of the study.
COLLEGE STATION, TX-In a new study published in PLoS Genetics, an international team of researchers report that two independent mutations are required to explain the development of the sex-linked barring pattern in chickens. Both mutations affect the function of CDKN2A, a tumor suppressor gene associated with melanoma in humans.
Leif Andersson
Leif Andersson, Uppsala University, Swedish University of Agricultural Sciences and Texas A&M University, led the study that illustrates how useful domestic animals are as models for evolutionary processes in nature. Andersson argues that a similar evolution of gene variants comprising multiple genetic changes affecting the function of a single gene is the rule rather than the exception in natural populations.
Research in pigmentation biology has made major advances the last 20 years in identifying genes controlling variation in pigmentation in mammals and birds; however, the most challenging question is still how color patterns are genetically controlled. Birds are outstanding as regards the diversity and complexity in color patterning, according to Andersson.
The study published April 7 has revealed the genetic basis for the striped feather characteristic of sex-linked barring. Sex-linked barring refers to the alternating of pigmented (usually red or black) and apigmented (white) stripes that occur on certain breeds of chickens.
One example is the French breed Coucou de Rennes, the name of which refers to the fact that its plumage color resembles the barring patterns present in the common cuckoo (Cuculus
canorus). The sex-linked barring locus is on the Z chromosome. In chickens, as well as in other birds, the male has chromosomes ZZ while females have ZW.
“Our data show that sex-linked barring is caused by two independent mutations that act together. One is a regulatory mutation that increases the expression of CDKN2A. The other changes the protein sequence and makes the protein less functionally active,” Andersson said. “We are sure that both mutations contribute to the sex-linked barring pattern because we have also studied chicken that only carry the regulatory mutation and they show a very pale plumage with only weak dark stripes. Thus, this represents an evolutionary process in which the regulatory mutation occurred first followed by the mutation affecting the protein structure. The combined effect of the two mutations causes an even more appealing phenotype for the human eye.
Coucou de Rennes, a French breed with the characteristic sex-linked barring phenotype. Photo: Hervé Ronné, Ecomusée du pays de Rennes.
Anderson also believes the most important reason for the extensive color variation among the domestic animals is that we appreciate its diversity, as long as the mutations underlying the variation are not causing health issues for the animals.
CDKN2A is a well-studied tumor suppressor gene that takes part in the regulation of cell division and cell survival. Mutations that inactivate CDKN2A are the most common explanation for familiar forms of melanomas in humans. However, the great majority of melanoma cases are not associated with a strong genetic risk factor.
“The gene variant underlying sex-linked barring has an opposite effect compared with the mutations causing melanoma in humans. Sex-linked barring is associated with a gene variant that makes CDKN2A more active, leading to a cyclic deficit of pigment cells and causing the white stripes during the development of an individual feather. It appears that pigment cells are particularly susceptible to changes in the function of CDKN2A as inactivating mutations in humans are associated with melanoma but rarely other cancer forms and activating mutations cause sex-linked barring in chickens but no other side effects are known,” said Doreen Schwochow Thalmann, PhD student and first author of the paper.
“It is fascinating that a large proportion of chickens used for egg and meat production around the world carry these mutations in a tumor suppressor gene. An example of such a breed is White Leghorn, which is one of the most prominent breeds used for egg production, but sex-linked barring is not apparent in these breeds because they also carry the dominant white color that eliminates all pigment production and masks the effect of sex-linked barring,” Andersson said.
