Growing Knowledge, Shrinking Tumors

An early interest in cancer research set Mahsa Zarei on a path to investigate treatments for rare and genetically linked conditions.

Story by Justin Agan

Dr. Mahsa Zarei in the lab
Dr. Mahsa Zarei

Ask most 12-year-old children what they want to be when they grow up and you are likely to get a variety of answers ranging from professional athlete to astronaut.

While doctor or scientist might be on that list as well, it is doubtful you would hear something as specific as cancer biologist.

Mahsa Zarei, Ph.D., however, was one of those rare children.

A Young Passion

When Zarei was 12 years old, she watched two of her close aunts fight cancer. One aunt benefited from early diagnosis and treatment; the second passed away.

Throughout this ordeal, Zarei’s mind raced with questions: How could she help her aunts? What kind of cancer did they have? What were the treatments?

As a result, she became an avid student of cancer, devouring cancer biology books.

“At 12, I wanted to know, what is cancer and what’s happening with the cancer?” Zarei recalls. “I learned most of the treatments for different types of cancer.”

Zarei’s interest in this career path never wavered.

She earned her undergraduate degree in medical bio-technology and her Ph.D. in cancer biology before accepting a postdoctoral research scientist position at the Sidney Kimmel Cancer Center in Philadelphia.

In 2016, she was the lead author on a study about pancreatic cancer and its ability to survive in the nutrient-poor conditions of the pancreas. The survivability of pancreatic cancer in such poor conditions has also seemed to translate to its resistance of current chemotherapy treatments.

“It’s like a cactus in a desert,” Zarei explains, “without any nutrients, but it’s still growing and aggressive.”

Zarei and her co-researchers found that one of the key proteins, HuR, allowed the cancer to survive in the nutrient-poor microenvironment of the pancreas. It also gave the cancer a resistance to chemotherapy drugs.

What Makes Cancer Tick

As the well-known Sun Tzu quote advises, “Know the enemy and know yourself, you need not fear the result of a hundred battles.”

Zarei has followed this advice in her research by knowing her enemy.

Cancer, in one of the broadest definitions of the term, refers to diseases that cause abnormal cells to divide without control and can invade nearby tissues, according to the National Cancer Institute.

Dr. Mahsa Zarei points out slides on a computer to Sneha Harishchandra
Dr. Mahsa Zarei and Sneha Harishchandra

Most know that there are many different types of cancer caused by any number of things or underlying conditions. Doctors and researchers have spent decades, even centuries, fighting cancer in all its forms.

Previous treatments, like chemotherapy, concentrated on killing the cancerous cells, but more recently, there has been a push to discover new ways of fighting it.

For the better part of her career, Zarei took the approach of figuring out how different types of cancer worked at a very basic level. By understanding the different pathways and processes that allow these cancers to live and grow, she can understand how better to fight them at that basic level.

After leaving the Sidney Kimmel Cancer Center, Zarei joined Harvard Medical School as a research scientist fellow. There, while working at the Brigham and Women’s Hospital, she learned about a pair of fraternal twins, one of whom had tumors in the kidney; no one could determine why these tumors were occurring.

“That’s why I worked so hard to try and understand her disease better and to come up with something,” she said.

After conducting genetic screening, Zarei’s lab found that the girl had a rare genetic disease that causes tumors that can affect the brain, kidneys, lungs, and heart. A mutation in a protein complex called tuberous sclerosis complex (TSC) is what causes the tumor growth.

In normal cells TSC1 and TSC2 help inhibit, or stop, another protein complex called mTORC1. The girl’s tumor cells lacked TSC2, so mTORC1 was hyper-activated. This caused the out-of-control division of cells and the growth of the tumor.

After finding the pathway involved in the rare genetic disease, Zarei and her co-researchers looked for ways to interrupt that pathway. They found a drug called THZ1 that was being used for different cancer types, including breast and ovarian cancer.

When tested on TSC-deficient cells and normal cells, THZ1 selectively targeted the TSC-deficient cells and caused them to die, but left healthy cells alone.

The established treatment for this disease is a drug called rapamycin. Rapamycin and drugs similar to it, commonly called rapalogs, reduce tumor size while the patient is taking the drug. However, as soon as the treatment ends, the tumors begin to grow again, which means that patients would have to remain on the drug indefinitely.

Zarei’s research found that THZ1 not only reduced tumor size, but it prevented re-growth of the tumors after stopping treatment. The U.S. Department of Defense now funds this study, and Cyrus Pharmaceutical Company has begun the first clinical trials of a derivative of THZ1.

“We are hoping that in the near future we can use this with a TSC patient,” Zarei said.

Sneha Harishchandra shows Dr. Mahsa Zarei a research poster
Sneha Harishchandra and Dr. Mahsa Zarei

Aggieland Bound

In 2018, Zarei moved to College Station with her husband, who had accepted a position in the Texas A&M University College of Engineering.

Zarei was then recruited by the Texas A&M College of Veterinary Medicine & Biomedical Sciences’ (CVM) Department of Veterinary Physiology & Pharmacology (VTPP).

“The evaluation of her cancer research program by the faculty in our department identified Dr. Zarei as a rising star and drove our intense interest in getting her to Texas A&M,” said VTPP department head Dr. Larry Suva. “She is an asset to our department, college, and university.”

Suva describes Zarei as a “role model for the energy and focus needed for faculty to succeed in academia.”

Since arriving at Texas A&M, Zarei has continued her research on TSC. In September, she published a paper on her research in the Journal of Experimental Medicine.

She has also renewed her research in pancreatic cancer with renowned cancer researcher Dr. Stephen Safe, also in VTPP. Together, they hope to find a new treatment that will reduce pancreatic cancer’s tolerance of its harsh microenvironment and chemotherapy.

Zarei is hopeful they will be able to publish their findings soon.

“Dr. Zarei has been great to work with,” Safe said. “She will be a prime candidate for a full faculty position.”

Zarei has turned an adolescent passion into a thriving career. In the future, she wants to continue finding answers in the lab that translate to the patients’ beds.

While she has mentored and taught students in her lab, including undergraduate researchers like Rachel E. Yan, one of the co-authors on Zarei’s most recent journal publication, she also hopes to return to the classroom soon, to pass on what she has learned.

Zarei wants to teach undergraduate and graduate classes, and “maybe a cancer biology class, if that’s possible.”

“My future goal is to be a well-known scientist, working on rare diseases and pancreatic cancer,” Zarei said. “I’m really passionate about having students to work with.”

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Note: This story originally appeared in the Spring 2020 edition of CVM Today.

For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

Cracking Into Undergraduate Research

Story by Dorian Martin

Erin O’Connor, Janisah Saripada, and Oula Eldow in the lab
From left: BIMS majors Erin O’Connor, Janisah Saripada, and Oula Eldow

Chickens’ eggs serve as the foundation for three innovative studies currently underway through the College of Veterinary Medicine & Biomedical Sciences’ groundbreaking initiatives, the Biomedical Research & Development Certificate and the Aggie Research Scholars Program. These programs are designed to help undergraduate students learn to do research.

Both are the brainchild of Dr. Christopher Quick, a professor in the Department of Veterinary Physiology & Pharmacology (VTPP). He started the programs in 2016, and they have grown to be the two largest undergraduate research programs at Texas A&M.

Although these two programs provided semester-long research opportunities to more than 800 undergraduates, they are not even close to meeting demand.

“Approximately one-quarter of undergraduates at Texas A&M get a chance to engage in research before graduating. The Aggie Research Program typically attracts three undergraduates for every research opportunity,” Quick said. “Last year, we could only support 50 percent of the undergraduates applying to the Biomedical Research Certificate Program. We recruit broadly, not to generate interest, but to make sure everyone has a fair shot at participating.”

“He showed up in the fall semester in one of my freshman seminar classes. You see this really eclectic professor come in shouting about this program,” said Janisah Saripada ’21, a biomedical sciences major who plans to attend medical school. “My friend and I said, ’Why don’t we try it out? It looks like a cool research opportunity.’”

Both programs, which serve students across Texas A&M University’s campus, use “research-intensive communities,” a model that involves teams of students coming together to work on research in groups instead of as individuals.

The model also encourages students to try a different research paradigm.

“Our research is more like, ‘See something, Test something and then get more questions from that test,’” Saripada said. “When you experiment and get more knowledge, your questions about the subject matter grow exponentially.”

Ultimately, this program prepares students for doing research in their careers, as well as graduate school.

“I think it’s a really good way to get hands-on experience because a lot of places want research, but it’s not being offered to undergraduates,” said animal science major Erin O’Connor ’21. “This is a good way for undergrads to get their foot in the door and get some actual real-world experience.”

Experiment 1: Radiation And Lymphatic Cells

BIMS major Oula Eldow ’21 and her team are using chicken eggs to study the effect of radiation on lymphatic vessels. The eggs, which are grown in flasks after being removed from their shells, allow students to easily witness changes.

“Being able to grow the eggs this way is very helpful because the blood vessels become really accessible,” Eldow said. “We can see how radiating these eggs will change the diameter of the lymphatic vessels. We also can see if these vessels grow differently when we radiate them versus if they weren’t radiated.”

The team believes this research will help them get a better understanding of radiation treatments used for cancer.

“When you radiate a tumor to stop its growth or kill its cells, the cells in the tumor get a very high dose of radiation, so they die or their growth is stopped,” said Eldow, who wants to become a pediatric primary care doctor with a goal of eventually working in a neonatal intensive care unit (NICU). “There is a side effect in the cells surrounding the tumor, such as lymphatic cells and blood cells. These cells get a smaller dose, so our experiment is on low-dose radiation. This low-dose radiation doesn’t kill these cells, but it does change the function. We want to see what these changes are.”

From left: BIMS majors Erin O’Connor, Janisah Saripada, and Oula Eldow using a microscope
From left: BIMS majors Erin O’Connor, Janisah Saripada, and Oula Eldow conduct research in the lab.

Experiment 2: Glucose And Diabetes

Saripada’s team developed their topic through meshing some initial research interests. Initially she was interested in researching how a ketogenic diet affects the body’s blood vessels. She met another student who was interested in looking at the effect of glucose in the body.

“I thought, ‘Oh, it would be a perfect idea to mesh these two projects together and look at one single disease, diabetes, because diabetes affects the levels of glucose and ketones in your body,’” the junior noted.

Using a chicken egg offers a useful way to study this problem.

“We add glucose, which is a type of sugar, and ketones, which are chemicals produced when your body doesn’t have enough insulin to convert sugar into energy,” Saripada said. “We’re basically trying to model diabetes, specifically gestational diabetes, using the Chick CAM model since it has many similarities to human embryonic development.”

Experiment 3: Sodium Fluoride And The Microvascular System

O’Connor and her team are using chicken eggs to try to detect changes in the microvascular structure through low doses of sodium fluoride.

“We chose this because we found other studies that showed that sodium fluoride affected embryo growth in frogs,” the Uvalde resident said. “We know that sodium fluoride can be in daily products, such as water and toothpaste, so we are trying to see what happens with low doses. Are they actually harmful or is it something that needs to be watched out for?”

The research may open doors for additional research on the microvascular system’s response to other teratogens.

“Teratogens are any agent or substance that affect the development of an embryo, such as malformations or birth defects,” O’Connor said. “This is important because we want to be able to identify any environmental factors that can pose a detrimental effect to a developing embryo or fetus.”

Growing Scholars And Leaders

These programs also give undergraduates the opportunities to develop skills that will serve them both inside and outside the research lab.

“The most valuable skills I’ve learned have been realizing how to work with team members and how to use everyone’s skills to really push the project in a positive direction in order to see results,” O’Connor said.

Eldow has enjoyed the opportunity to grow as both a researcher and a leader.

“This research is something that I’m very passionate about,” she said. “It’s helped me grow as a leader and grow as a student.”

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Note: This story originally appeared in the Spring 2020 edition of CVM Today.

For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

CVM Researcher Discovers Domestic Horse Breed Has Third-Lowest Genetic Diversity

Story by Margaret Preigh

Dr. Gus Cothran
Dr. Gus Cothran

A recent study by Dr. Gus Cothran, professor emeritus at the Texas A&M School of Veterinary Medicine & Biomedical Sciences (CVM), has found that the Cleveland Bay (CB) horse breed has the third-lowest genetic variation level of domestic horses, ranking above only the notoriously inbred Friesian and Clydesdale breeds. This lack of genetic diversity puts the breed at risk for a variety of health conditions.

Genetic variation refers to the differences between different individuals’ DNA codes. Populations where there is high genetic diversity will have a wider range of different traits and will be more stable, in part because disease traits will be more diluted. In populations with low genetic variation, many individuals will have the same traits and will be more vulnerable to disease.

The CB is the United Kingdom’s oldest established horse breed and the only native warm-blood horse in the region. Used for recreational riding, driving, and equestrian competition, the CB is considered a critically endangered breed by the Livestock Conservancy.

Because maintaining genetic diversity within the breed is important to securing the horses’ future, Cothran and his team worked to gain comprehensive genetic information about the breed to develop more effective conservation and breeding strategies.

In this study, published in Diversity, researchers genotyped hair from 90 different CB horses and analyzed their data for certain genetic markers. These samples were then compared to each other, as well as to samples from other horse breeds to establish the genetic diversity within the breed and between other breeds.

Both the heterozygosity and mean allele number for the breed were below average, indicating lower than average genetic diversity within the breed. This low genetic diversity should be seen as a red flag for possible health conditions.

“Low diversity is a marker for inbreeding, which can cause low fertility or any number of hereditary diseases or deformities,” Cothran said. “With overall population numbers for the breed being so small, such problems could rapidly lead to the extinction of the breed.”

The Cleveland Bay Horse Society of North America estimates that only around 900 CB purebreds exist globally. Such low population numbers mean the breed is considered to be critically rare.

Cleveland Bay horses pulling a carriage
Cleveland Bay horses

This study also evaluated the diversity between the CB and other breeds using a majority-rule consensus tree, a type of analysis that shows an estimate of how different clades, or groups of organisms sharing a common ancestor, might fit together on their ancestral tree.

Cothran and his team’s analysis found that the CB did not show a strong relationship with any other breeds, including other breeds within the same clade. Though this could be a result of the low genetic diversity within the breed, these data suggest that the CB is genetically unique from other breeds. These findings place emphasis on the importance of CB horses as a genetic resource.

“The CB is an unusual horse in that it is a fairly large sized horse but it is built like a riding horse rather than a draft horse,” Cothran said, noting the uniqueness of the breed. “It frequently is bred to other breeds such as the Thoroughbred to create eventing or jumping horses, although this is a potential threat to maintaining diversity in the CB.”

Cothran hopes his research will help to inform conservation efforts supporting the longevity of the CB breed, as well as inform breeders on how they can more responsibly further their horses’ genetic lines.

“If any evidence of inbreeding is observed, breeders should report it to scientists for further analysis,” Cothran said. “Efforts should be made to keep the numbers of CB horses as high as possible and to monitor breeding practices to minimize inbreeding and loss of variability.”

“Domestic animals, including horses, are also at risk of declining populations, just like endangered species, but research can help determine which populations (breeds) are at risk and provide possible directions to help reduce risks or consequences,” he said.

Though CB horses are currently at risk, Cothran remains optimistic that careful monitoring and management of the breed can preserve them as a cultural and genetic resource for years to come.

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of CVM Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

CVM Researcher Finds Chickens, Pigeons Share Mutation For Feathered Feet

Story by Margaret Preigh

Postdoctoral research associate Dr. Jingyi Li, holding a chicken, in a barn with Dr. Leif Andersson
Postdoctoral research associate Dr. Jingyi Li and Dr. Leif Andersson

A team of researchers including Dr. Leif Andersson, a professor at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), has found that parallel evolution between domesticated chickens and pigeons has resulted in regulatory mutations in the same genes that govern foot feathering in both species.

Poultry geneticists have long studied the inheritance of a prized fancy chicken breeding trait—feathered legs.

The foot feathering trait in question, known scientifically as ptilopody, can be observed in domesticated and wild avian species and is characterized by the partial or complete development of feathers on the skin of the ankles and feet.

“Foot feathering is an interesting case since, although it is a very recognizable trait that can be very easily selected to fixation in breeds, it is, in fact, not a monogenic trait, caused by a single gene,” Andersson said.

In evolution, parallel evolution is known as the independent development of similar physical traits in separate but related lineages. In other words, when faced with adaptation, nature can go to the same “genetic toolbox” to come up with new solutions.

In a study published April 28th in Molecular Biology and Evolution, Andersson and co-authors report that the same two genes, Tbx5 and Pitx1, responsible for foot feather patterning in pigeons are also responsible for foot feather patterning in domesticated chickens.

Andersson and his colleagues set out to find which genes and specific mutations correspond to two previously studied alleles, or gene variants, known as Pti-1 and Pti-2, which have been previously found to contribute to foot feathering in chickens—and if these corresponding genes and mutations were the same as those previously identified as governing foot feathering in pigeons.

They employed controlled breeding to generate a three-generation mapping population of chickens, with a mix of feathered and “clean” legs. The research team then used genetic analysis to spot mutations and genetically characterize 167 chicken populations with or without feathered legs.

Two roosters with feathered feet
Roosters with feathered feet

“The identification of causal mutations in non-coding parts of vertebrate genomes is challenging, due to the difficulty in deducing or experimentally proving functional significance,” Andersson said. “Here we have presented strong genetic evidence for causality for two non-coding mutations affecting the feathered leg phenotype in domestic chicken using a very large data-set from chicken with or without feathered legs.”

Thus, not only are the same genes involved in foot feathering phenotypes in pigeons and chickens, but the nature of the mutations are also very much the same, at least in the case of Pitx1.

The study reveals a remarkable convergence in the evolution of the feathered leg phenotype in domestic chickens and domestic pigeons as this trait is caused by non-coding mutations in the regulatory instructions of the same two genes. The results show that ptilopody has evolved by running on separate but parallel tracks in chicken and pigeon.

“These two cases add to a growing list of regulatory mutations controlling phenotypic traits in domestic animals by altering the expression of important transcription factors,” Andersson said. “The present study also illustrates that novel phenotypic traits in domestic animals are often caused by the same mutations across divergent populations because favored mutations have been spread from population to population due to strong phenotypic selection.”

This study can also help future researchers by providing a road map for how to identify causal mutations from large datasets and by providing gene candidates that warrant further investigation in regard to leg feathering and other traits in different species.

“The extensive collection of whole genome sequence data, which is publicly available provides a powerful resource to identify genomic regions and corresponding causal mutations associated with these phenotypes as successfully accomplished in this study,” Andersson said.

“Furthermore, feathered legs occur in many other bird species, for instance, in most owls but not in all. If you would like to study the genetic basis for variation in leg feathering within a species or between closely related species, Tbx5 and Pitx1 are the obvious candidate genes to start with.”

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of CVM Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

Challenging The Norms

Dr. Michael Golding’s approach to his work both in the lab and the classroom is predicated by asking the questions very few people consider.

Story by Courtney Adams

Dr. Michael Golding and others in his lab
Dr. Michael Golding, Dr. Nicole Mehta, Yudishtar Bedi, Alexis Roach, and Kara Thomas

Today, anybody who sells alcoholic beverages must adhere a label to their product with the following statement: “GOVERNMENT WARNING: (1) According to the Surgeon General, women should not drink alcoholic beverages during pregnancy because of the risk of birth defects.”

The statement focuses on women—with no mention of men.

This oversight is to no fault of the U.S. Surgeon General because it is widely accepted that fetal alcohol syndrome can be blamed solely on the woman. However, Dr. Michael C. Golding and his research team at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM) are challenging that very principle.

Becoming A Scientist

Growing up on a farm in Canada, Golding did not envision himself as a researcher.

“I’ve always been fascinated with understanding how things work and why, so I think that component of being curious was always with me,” he said. “But I don’t think that I ever consciously wanted to be a scientist.”

Intending to go to medical school, Golding attended college at the University of Western Ontario as a biology major. A developmental biology course he took during his third year, however, changed his career trajectory.

“The lecture the professor gave on this thing called Spemann organizer (a cluster of cells responsible for the induction of the neural tissue during development) just blew my mind,” Golding said. “This led me into this fascination with development and understanding how it is that our bodies are organized and programmed.”

After graduating with his bachelor’s degree in 2000, Golding decided to pursue his Ph.D. and left Canada to study under Dr. Mark Westhusin, a professor in the CVM’s Department of Veterinary Physiology & Pharmacology (VTPP), with whom Golding spent his early years examining the development of cloned embryos.

After completing his doctorate, Golding left Texas A&M to complete two postdoctoral fellowships, one at Cold Spring Harbor Labs and one at Children’s Health Research Institute at the University of Western Ontario, before eventually coming back to Texas A&M.

Fighting The Dogma

Golding, now an associate professor in VTPP, currently focuses on the effects that male alcohol consumption has on the development of fetal alcohol syndrome (FAS). Characterized by various mental and physical defects, FAS signs can include facial deformities, learning disabilities, and growth abnormalities.

“It became very clear to me as I started this research that there was a piece of this that was missing,” Golding said.

Dr. Michael Golding and Alexis Roach working in the lab
Dr. Michael Golding and Alexis Roach

So, in 2012, he asked a simple question—Does a father’s drinking affect the development of the fetus?

Because the idea challenged a societal norm, he was met with some pushback and funding was difficult to come by at first.

“I would get comments back on my grants, ’Why are we doing this? Fetal alcohol syndrome is the woman’s fault,’” Golding said. “They were just of the mind this is not something that should be investigated.”

But Golding was determined that he had a question worth asking.

“I took the components that they liked and stitched them together into a smaller grant,” he said.

Finally, in 2014, he received a National Institutes of Health (NIH) grant to initiate his research, a project in which Golding simply gave alcohol to male mice and mated them with naive female mice.

“The fetuses that were sired by the alcohol-exposed males were smaller, and their placentas were abnormal,” he said. “We had this just very blatant, not complicated phenotype.”

The grant lasted for two years, but it took another three to convince anyone that this was worth exploring further.

“That’s where we started, and we’ve been chasing that ever since,” Golding said.

In June 2019, the Keck Foundation granted $900,000 to Golding and his colleagues to continue the research.

“The big thing that they wanted was something that questioned the paradigm,” Golding said. “I put up the Surgeon General’s Warning and I was like, ’Look, this is what I’m questioning; it’s absolutely going against the dogma.’ They loved it.

“Ultimately, I want to try and figure out how dad’s drinking fits into the larger picture of fetal health, adolescent health, and then, ultimately, adult health,” Golding said. “Any offspring is the sum total of their experience in utero—their mother’s exposures prior to conception or during pregnancy, her diet, and I want to find out what dad’s role is in that piece of the pie.”

Kara Thomas working in the lab
Kara Thomas

Currently, Golding has three graduate students and a postdoctoral fellow in his laboratory. Together, they are working to define the signaling (communication within the cell) and epigenetic mechanisms (those arising from nongenetic influences on gene expression) for how alcohol interferes with developmental processes.

“I’ve had people come to me and say, ‘How much do you have to drink to see a problem?’” Golding said. “The truth of the matter is we have no idea how alcohol is doing this, and that’s kind of what the central pillar of my research is trying to figure out.”

“Dr. Golding’s pretty open to challenging the standard,” said Yudhishtar Bedi, a Ph.D. student in Golding’s lab. “When we do find data that says something—the opposite of what other people have found and maybe two or three labs have found—he doesn’t back down from it. He’s always showing me the way to be, I guess, fearless in a way.”

Students working in Golding’s lab are also motivated by the potential for their research to benefit the public.

“I feel like a lot of the things that we’re doing right now have a lot of real-world impact,” postdoctoral fellow Nicole Mehta, Ph.D., said.

One may question if Golding’s research has had any influence on his parenting ideology—he has three young children: two older boys and a daughter.

“I don’t think I could disentangle being a dad from being a scientist,” Golding said. “I cannot simply say to my daughter, ‘OK, you need to be healthy,’ whereas to the other two, ‘You can go out and do whatever you want.’”

Teaching The Next Generation

When Golding is not in the lab, he can be found teaching classes at the CVM. Currently, he teaches “Fetal and Embryo Physiology,” a course both undergraduates and graduates can take together, and “Epigenetics & Systems Physiology,” currently only offered to graduate students.

In his classes, Golding says he enjoys dispelling myths students have picked up over the years about reproduction.

Dr. Michael Golding, Kara Thomas, Alexis Roach, Dr. Nicole Mehta, and Yudishtar Bedi working in the lab
Dr. Michael Golding, Kara Thomas, Alexis Roach, Dr. Nicole Mehta, and Yudishtar Bedi

“I consider it a special thrill,” he said. “They have certain facts and statistics that they’ve picked up on the playground through school that are absolutely not true.”

One former student, Katie Poulter ’15, remembers Golding’s class as detailed and difficult, but that Golding was willing to spend extra time on anything that was troubling for students.

“I could tell he loved what he was teaching about,” Poulter said. “That made a big difference.”

When teaching complicated subjects such as human development, Golding tries to tell stories to help students remember the details for years to come.

“I make sure I have a section on Spemann’s organizer,” he said. “It’s good to go back to my inspiration.”

Golding’s teaching philosophy speaks to his desire for his students to succeed.

“I consider the teacher to be a person who’s giving their sales pitch—‘I want you to become like me,’” he said.

In his research lab, Golding teaches by training the next generation of scientists.

“He’s so nice and down to earth. He tries to get to know us and have that mentor/mentee relationship that everyone wants,” said Kara Thomas, a biomedical sciences (BIMS) master’s student in Golding’s lab.

Golding likes making students into skeptics.

“The other component of my professional life that I really enjoy is to bring students in and say, ‘you were taught these things, but now you need to question everything,’” he said.

“That growth is very rewarding to see,” Golding said. “I have students in the lab who come in and they get onboard with questioning different things and then after a couple years, it’s like they don’t even need me.”

Golding has had two students proceed to prestigious postdoctoral fellowships—one at MD Anderson and the other at University of California, Irvine. A third student is currently working at Seattle Children’s Hospital.

A Great Place To Be Fearless

Golding believes his research would be more challenging without his colleagues at the CVM.

“There’s such a breadth of skillsets and interests here at A&M that you can ask questions, like the ones I’m asking, and you don’t have to go too far for help,” Golding said. “The environment is stimulating, it’s diverse, and it is highly conducive to good research.”

If there was only one concept the public gains from his research, Golding hopes it is that chronic drinking has an impact on not only their own well-being but also their offspring.

“Males have an important role in the health of their offspring beyond simply contributing healthy genes,” Golding explains.

He hopes that one day he will pick up a beer bottle to find the Surgeon General’s warning label has changed to incorporate men, too.

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Note: This story originally appeared in the Spring 2020 edition of CVM Today.

For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

Today’s Research, Tomorrow’s Cure

Story by Megan Myers

Duc Nguyen and Dr. Dana Gaddy next to a microscope
Duc Nguyen and Dr. Dana Gaddy

For Duc Nguyen, research is one of the most fascinating aspects of veterinary medicine.

While he initially intended to be a child behavioral psychologist when he began studying psychology at the University of Houston, in the final year of his undergraduate degree, Nguyen suddenly realized that his true passion was for animals and veterinary medicine.

“I always had an interest and love for animals, but I had this strange fear that if I made a career out of it, my love for animals would go away,” Nguyen said. “My wife, who was my girlfriend at the time, said I was being irrational and convinced me to go for it. Women are always right, so I’m glad I listened to her!”

Nguyen never really considered other veterinary schools outside of Texas A&M; he wanted to stay close to his mother in Houston, where he lived for the majority of his life after emigrating from the small province of Tay-Ninh, Vietnam.

“My mom is a single parent and isn’t fluent in English so Texas A&M allows me to be closer to her if she ever needs my help,” he said.

Once Nguyen decided he wanted to become an Aggie veterinarian, he began looking for ways to make his application stand out. He soon became involved in research work in an ophthalmology lab at the University of Texas Health Science Center.

His lab studied zebrafish and mouse genetics to gain insight on a genetic mutation that causes Retinitis Pigmentosa, a disease in humans that causes death of the photoreceptor cells in the eye, which translate light into electrical signals that the brain can understand.

While mammals only have photoreceptor cells, zebrafish also have rod progenitor cells, which have the ability to repair retinal damage.

“Mammalian retinas have no mechanism to reverse photoreceptor cell death, but by examining the incredibly advantageous, regenerative properties that zebrafish rod progenitor cells have, the study could lead to finding therapeutic treatments for one of the leading causes of blindness,” Nguyen said.

From this experience, Nguyen discovered his love for research and laboratory animal medicine.

“I had an amazing principal investigator who always encouraged me to attend journal clubs and research seminars, which really cultivated my interest in biomedical research,” he said. “I also got to work extensively with the animals and really gained an appreciation for what they give to science. I definitely lucked into the field.”

Once he began his veterinary classes, Nguyen continued to look for opportunities to get involved in research. Since then, he has learned to appreciate the role that lab animal veterinarians play in supporting and protecting animals.

In the summer of 2017, he was accepted to the CVM’s Veterinary Medical Scientist Research Training Program to study cellular response at the site of injury of Staphylococcus aureus infected femurs.

Duc Nguyen looks into a microscope while Dr. Dana Gaddy watches
Duc Nguyen and Dr. Dana Gaddy

Staphylococcus aureus, or staph, as it is often known, is a common germ that can lead to serious, and sometimes fatal, infections if it makes its way to the wrong place. Better understanding the cellular response to this infection will help equip healthcare professionals with more effective treatment methods.

“I gained so many invaluable experiences from the research training program,” Nguyen said. “I learned a ton and had first-hand experience writing a research proposal, abstract, and manuscript; producing a poster; and getting to present that poster at a research seminar.

“I also traveled to the National Institutes of Health in Washington, D.C., to present my poster with my friends, which was really fun.”

After graduation, Nguyen hopes to return to Houston to work as a clinical lab animal veterinarian in academia and collaborate on many research projects.

“I enjoy having the ability to be involved and up-to-date with the latest biomedical research, as well as having access to a very diverse patient population,” he said. “I like all fields of research, but I have a special interest in cancer research.”

“Even from my limited experience in research, I’ve witnessed some incredible breakthroughs in cancer research, which is really exciting,” he said. “However, there are still so many more questions we can answer. I can’t say I will be the person to cure cancer, but as a lab animal veterinarian, my hope is that I can serve as a conduit for the field of cancer research.”

In all areas of research, lab animal veterinarians can have a big impact on the health and safety of animals involved and on the research itself. By responsibly caring for lab animals, Nguyen’s contributions to today’s research will support the future of both animal and human medicine.

“If we want to continue developing drugs, medical devices, and diagnostic tools that help both humans and animals, we have to all work together to raise awareness of the vital role animals play in biomedical research,” Nguyen said. “By doing so, we can continue to save lives.”

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Note: This story originally appeared in the Spring 2020 edition of CVM Today.

For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

CVM Researcher Fights Antibiotic Resistance, Improves Foal Health

Story by Margaret Preigh

Dr. Noah Cohen with a foal
Dr. Noah Cohen

Dr. Noah Cohen, the Patsy Link Chair in Equine Research at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), has identified an alternative treatment for foal pneumonia that avoids the use of often over-prescribed antibiotics.

In research funded by the Morris Animal Foundation, Cohen and collaborators found that gallium maltolate (GaM), a metal-based compound with antimicrobial and anti-inflammatory properties, resolved subclinical pneumonia (i.e., pneumonia identified in foals that did not have clinical signs, such as fever, coughing, a depressed attitude, etc.) without increasing the number or diversity of antibiotic-resistant bacteria in the foals’ fecal samples.

Antibiotic resistance is a pressing issue in today’s world. Overuse and incorrect use of antibiotics have increased the prevalence and diversity of bacteria that are resistant to antibiotic medications. This creates “superbugs” that doctors have no way of combatting, opening vulnerabilities in human health, the health of our animals, and the health of our food system.

Foal pneumonia is one of the leading causes of death and disease in foals and has no licensed vaccine. It is often caused by the bacteria Rhodococcus equi (R. equi), which occur naturally in soil.

Pneumonia caused by R. equi is insidious, meaning it progresses gradually and is well established by the time symptoms appear, so many farms screen foals using chest ultrasound examinations to find foals that are developing pneumonia before they show clinical signs of disease.

Veterinarians then treat the foals that have chest lesions indicating pneumonia. However, because many of these foals that have chest lesions seen on ultrasound won’t go on to develop pneumonia, a large proportion of foals get treated with antibiotics needlessly.

“While that treatment strategy saves lives in the short term, it’s really driving this resistance problem because, for every one foal that needs treatment, several foals that don’t need treatment wind up getting antibiotics,” Cohen said.

In this study, published in the journal Scientific Reports, researchers from Texas A&M and the University of Georgia investigated the use of GaM as an alternative to a macrolide antibiotic plus rifampin (MaR), an antibiotic combination that is the standard used for treating R. equi foal pneumonia.

Foals with signs of subclinical pneumonia were given either GaM or MaR for two weeks.

Dr. Noah Cohen and graduate student Susie Kahn with a foal
Dr. Noah Cohen and graduate student Susie Kahn

After two weeks, foals treated with MaR displayed an increase in their number and diversity of antibiotic-resistant bacteria in their fecal samples. Alarmingly, many of these bacteria were resistant to multiple drugs and antibiotics.

In foals treated with GaM, however, bacteria collected from fecal samples showed no change in the number or diversity of antibiotic-resistant bacteria. This finding suggests that while treatment with MaR promotes the abundance of antibiotic resistant bacteria, treatment with GaM did not affect the amount of these harmful germs.

This is important because horses are often kept in groups; therefore, the fecal bacteria of one animal may infect or colonize another healthy foal living on the same soil.

Another concern of using MaR in the treatment of foal pneumonia is that the excrement of horses taking this medication may contain traces of unabsorbed antibiotic. This study showed that antibiotic entering soil will increase selection for bacteria that are resistant in the soil.

Researchers hope to next test the effectiveness of GaM on foals that are clinically infected with R. equi.

This study comes at a vital time, as bacteria evolve faster than scientists develop new drugs. Antibiotic alternatives, such as the substance investigated by Cohen and his colleagues, are integral to ensuring the future of our food systems, our animal friends, and our own health.

“The World Health Organization has identified antimicrobial resistance as a top threat to human health,” Cohen said. “There is an urgent need in human and veterinary medicine to identify alternative antimicrobials because bacteria can evolve resistance so rapidly, and often to multiple classes of drugs.”

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of CVM Communications, Texas A&M College of Veterinary Medicine & Biomedical Science; jgauntt@cvm.tamu.edu; 979-862-4216

CVM Study Reveals Potential Health Benefits Of Coconut Oil

Story by Madeline Patton

Dr. Annie Newell-Fugate
Dr. Annie Newell-Fugate

Many so-called “super-food” fads come and go before the scientific community has a chance to study them, but new research suggests that one recent trend—coconut oil—may mitigate the features of metabolic syndrome.

Dr. Annie Newell-Fugate, an assistant professor in the Texas A&M College of Veterinary Medicine & Biomedical Sciences’ (CVM) Department of Veterinary Physiology and Pharmacology (VTPP), recently presented research that offers insight into the potential benefits of dietary coconut oil.

Approximately 40 percent of American women are obese and are at risk for metabolic syndrome, which is characterized by increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol and triglyceride levels, all of which increase the risk of heart disease, stroke, and type 2 diabetes.

Newell-Fugate’s work focuses on improving the metabolic health of obese females struggling with metabolic syndrome, rather than focusing on weight loss alone.

“Most people in the nutrition and kinesiology fields are focused on weight loss to improve the health of obese patients,” Newell-Fugate said. “There are researchers looking at different types of diets—like the Mediterranean diet or Keto diet—and their effects on weight loss and overall health. However, the notion that you can potentially change the diet without causing weight loss yet still improve an individual’s health has not received much attention.”

In her study, Newell-Fugate and her team sought to determine whether a high-fat diet that incorporates coconut oil, a plant fat source, could improve the overall health and metabolism of obese females in comparison to the health of obese females fed a Western-style diet containing lard, an animal fat source.

Over an eight-month period, Newell-Fugate and her team fed two groups of female pigs high-fat diets consisting of 4,500 calories per pig per day. Both the Western-style diet and the coconut oil diet received 9 percent of their daily caloric intake from their respective fat sources. A third group was fed a low-calorie, lean diet as a control.

“We established each animal’s baseline before they went on their diet,” Newell-Fugate said. “Then, we assessed their blood glucose, cholesterol, and weight throughout the study; at the end, we were able to compare how much difference each of the diets had on these metabolic health parameters over time.”

The researchers found that the obese group, which received coconut oil had decreased features of metabolic syndrome, specifically with respect to cholesterol and blood glucose levels, in comparison to the obese group fed the lard-containing diet.

“Our research suggests that dietary coconut oil may be used in conjunction with lifestyle modifications and anti-diabetic drugs to treat metabolic syndrome, at least in women, with obesity,” Newell-Fugate said.

“The one thing I set out to understand with this particular project is determine whether coconut oil can modulate these metabolic parameters despite the fact that the females are still obese?” she said. “And the answer is yes.”

She recently presented her findings virtually at the annual Endocrine Society meeting, ENDO 2020.

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of CVM Communications, Texas A&M College of Veterinary Medicine & Biomedical Science; jgauntt@cvm.tamu.edu; 979-862-4216

CVM Faculty Members to Promote Canine Health with New Research Grants

Story by Megan Myers

Drs. Nick and Unity Jeffery, a husband-and-wife duo at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), have received canine health research grants from the American Kennel Club’s (AKC) Canine Health Foundation (CHF).

Dr. Unity Jeffery
Dr. Unity Jeffery

In celebration of its 25th anniversary, the AKC CHF awarded more than $2.1 million in 36 new canine health research grants in February. The selected projects were chosen based on their ability to meet the highest scientific standards and to have the greatest potential to advance the health of all dogs.

In her Dogs Helping Dogs Laboratory, Unity Jeffery, an assistant professor in the CVM’s Department of Veterinary Pathobiology (VTPB), will conduct research for her grant “Tumor-educated Platelets: A Minimally Invasive Liquid Biopsy for Early Cancer Diagnosis.”

Studies in human medicine have shown that RNA in blood platelets is a promising marker for various types of cancer.

Unity Jeffery’s study, in collaboration with Drs. Emma Warry, Jonathan Lidbury, and Chris Dolan, from the CVM’s Department of Small Animal Clinical Sciences (VSCS), will act as a proof of principle to determine if this information is translational into canine medicine.

If so, her research may be the first step in developing a blood-based screening test or liquid biopsy for canine cancer.

“One of the big problems with cancer in dogs is that because dogs can’t talk, they can’t let us know when they’re starting to feel just a little bit unwell or show very mild symptoms,” she said. “That means that we often don’t diagnose cancer in dogs until very late, when the cancer’s already widespread throughout the body.”

By using a test that can detect cancer earlier, veterinarians may be able to use more targeted treatment protocols that have reduced side effects.

“The hope of early diagnosis is that maybe that’s your chance to fully eliminate the cancer rather than just prolong life,” she said.

Dr. Nick Jeffery
Dr. Nick Jeffery

Meanwhile, CVM professor and neurologist Nick Jeffery will be working to extend results from a previous research project for his grant “Clinical Trial of Prevotella histicola Supplementation to Ameliorate Meningoencephalomyelitis of Unknown Origin (MUO).”

In a previous project, Nick Jeffery found that dogs with MUO, a disease of the central nervous system that resembles multiple sclerosis in humans, have an unusual balance of bacteria in their guts. Particularly, one bacteria that is known for controlling inflammation was consistently at lower levels.

His project will focus on providing supplements of that reduced bacteria to dogs with MUO to hopefully improve the disease’s outcome.

“We’re going to culture the bacteria and then put them into capsules that dogs can take every day,” he said. “The idea is that it will help us get better control of the disease, which is quite serious and quite a lot of dogs will die of it. We’re hoping that by supplementing with this bacteria, we might improve their survival.”

In addition to improving the survival of dogs with MUO, the bacterial supplement could also provide a way to reduce the use of immunosuppressive drugs, improving the dogs’ overall health and wellbeing.

Similar to the translational aspect of Unity Jeffery’s project, Nick’s may also one day play a role in human medicine by suggesting a new treatment method for multiple sclerosis.

“I was very pleased to get the grant, especially since it was a follow up on a previous study,” he said. “It’s fantastic to try out bacterial supplementation. This sort of approach is pretty new in all medicine, so it’s a great opportunity to test the idea and also try to fix dogs that have got a very serious condition.”

“I’m very grateful to the AKC Canine Health Foundation and the owners and breeders who donate to the charity,” Unity Jeffery said. “My Dogs Helping Dogs Lab, where we use canine patients and healthy volunteers to try to better diagnose and treat common canine diseases, fits really nicely with the AKC’s mission to improve the health of both pedigree dogs and the whole canine population. It’s a charity that I feel very honored to be funded by and very grateful for their continuing support.

“Nick and I have pet dogs at home and we love our dogs; they’re our family,” she said. “For me, I feel that I do the same type of research for my patients as a human doctor would do for theirs, and that’s what’s great about working in a veterinary school and having the opportunity to obtain funding from sources like the AKC.”

About the AKC CHF

Since 1995, the AKC Canine Health Foundation has leveraged the power of science to address the health needs of all dogs. With more than $56 million in funding to date, the Foundation provides grants for the highest quality canine health research and shares information on the discoveries that help prevent, treat and cure canine diseases. The Foundation meets and exceeds industry standards for fiscal responsibility, as demonstrated by their highest four-star Charity Navigator rating and GuideStar Platinum Seal of Transparency. Learn more at www.akcchf.org.

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216

CVM Researcher to Study Tick Vaccines in Brazil as Fulbright Recipient

Dr. Albert Mulenga in his lab
Dr. Albert Mulenga

Story by Margaret Preigh

Dr. Albert Mulenga, a professor in the Texas A&M College of Veterinary Medicine & Biomedical Sciences’ (CVM) Department of Veterinary Pathobiology (VTPB), will spend four months continuing his research on tick vaccines in Brazil thanks to a Fulbright award.

The prestigious award will support Mulenga’s research abroad, during which he will work alongside researchers in Porto Alegre, Brazil, at the University Rio Grande do Sul. In addition to his research, Mulenga will teach a course and advise a Brazilian graduate student who will be helping him conduct his research on tick vaccines.

Under the Fulbright Program, Mulenga is tasked with “increasing mutual understanding between the people of the United States and the people of other countries,” according to the J. William Fulbright Foreign Scholarship Board.

This directive ties in closely to what Mulenga, as an immigrant, feels his career represents.

“I represent what is possible in the United States,” he said. “When I came to this country, I started my career as a postdoctoral fellow, and now I’ve risen all the way to a professor and associate head of a department. Once you put your mind to it, you can achieve what you want.”

The Fulbright program is the largest and most diverse international exchange program; recipients are carefully selected on the basis of their leadership and contributions to society under the supervision of a 12-member presidentially appointed board.

Alumni of the program include 60 Nobel Laureates, 86 Pulitzer Prize winners, 74 MacArthur Fellows, and countless other bright and influential members of society.

Mulenga is both honored and humbled to join their ranks.

“These former recipients have gone into leadership positions, have done amazing things after the Fulbright,” he said. “The people who have gone through this program have benefited. I want to make sure that I take advantage of those opportunities.”

Dr. Ramesh Vemulapalli, Professor and Department Head of VTPB at the CVM, recommended Mulenga for the award and believes that Mulenga will find his place among previous recipients.

“Dr. Mulenga’s scholarly accomplishments are a result of his scientific creativity, tenacity, and hard work,” Vemulapalli said. “He represents the best of American values. We are very proud that he is recognized as a Fulbright Scholar.”

Mulenga’s research will be instrumental in improving cattle health in Brazil and the United States, the two leading beef producers globally. According to the Organization for Economic Co-operation and Development (OECD), global consumption of beef is 14.5 kg per person each year. As developing countries continue to grow economically, global meat consumption is expected to increase.

“Brazil’s cattle industry is huge,” Mulenga said. “Ticks and tick-borne disease are a very big impediment, so they are trying to find solutions. Coming from Texas, it’s a win-win. If I’m successful in this project, the data could be directly applicable here.”

Currently, Mulenga is conducting research to develop a vaccine against cattle fever ticks under Kleberg Foundation support. This builds on his National Institutes of Health-funded research to understand how the Lonestar tick and the blacklegged tick transmit human tick-borne diseases. He believes that insight gained from his Fulbright project in Brazil will also translate to this ongoing study.

The new vein of research Mulenga will undertake in Brazil will investigate a novel way to empirically evaluate antigens for new tick vaccines. Current vaccine development models involve first selecting an antigen, then building a vaccine off of that molecule.

His research in Brazil will be unique in that he will be allowed to work in much closer proximity to these ticks than United States regulations would allow.

“There is a big benefit because, in Brazil, I can directly observe cattle fever parasites,” he said. “My collaborator in Brazil is allowed to work with infected ticks; I’m not allowed. With uninfected or infected ticks, we are restricted to working in a quarantine zone between the border of Texas and Mexico.”

Though Mulenga’s research and work as an ambassador will build off of his previous experiences, he looks forward to combining his strengths in research and communication to act as an academic representative of our country.

“At a scientific meeting, I’m just focused on my research,” he said. “Under this program, I also have to communicate the values that allowed me to come to this country and become a member of this society, do my work, and be able to get this award.”

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For more information about the Texas A&M College of Veterinary Medicine & Biomedical Sciences, please visit our website at vetmed.tamu.edu or join us on FacebookInstagram, and Twitter.

Contact Information: Jennifer Gauntt, Director of Communications, Texas A&M College of Veterinary Medicine & Biomedical Sciences; jgauntt@cvm.tamu.edu; 979-862-4216