TXBiobytes from Texas Biomed

Deepak Kaushal, Ph.D.

Co-infections with HIV and TB are a persistent health problem. In otherwise health people with latent TB, only 5% will go on to develop active tuberculosis. In HIV/AIDS patients, the risk of developing active TB increases ten-fold to 50%.

Workers in Dr. Kaushal's lab take part in TB/HIV experiments.

About a third of everyone who has HIV dies of complications from TB. Professor and Director of the Southwest National Primate Research Center, Deepak Kaushal, Ph.D. a Texas Biomed researcher, recently published a collaborative study pinpointing a possible new avenue of protection for these patients.

More than 30 years ago, the National Institutes of Health funded a large-scale project called the Strong Heart Study. It was designed to look at particular risk factors for heart disease in the Native American population. What Texas Biomed scientists and collaborators around the country have found is impacting all of us.

13 tribes in several states are taking part in the Strong Heart Study which just received funding for another seven years.

Associate Professor Shelley Cole, Ph.D., of the Population Health Program explains the science – and the humanity – of this years-long research project.

Biofilm is a thin, slimy film of bacteria.

Daniel Wozniak, Ph.D., of The Ohio State University is a recognized expert in the field of infectious diseases. Recently, he visited Texas Biomed as the keynote speaker at the Research Symposium 2019.

Dr. Wozniak is looking for new ways to treat stubborn infections that often make life miserable for patients or ultimately claim their lives. These secondary infections are the kinds of diseases caused by bacteria that often plague vulnerable patients. He specializes in the kinds of infections suffered by patients with cystic fibrosis and wound care patients.

Daniel Wozniak, Ph.D., served as keynote speaker at Texas BIomed's Research Symposium 2019.

Bacteria that cause chronic infections in patients create problems that add up to more than $25 billion dollars in health care every year in the U.S.

Part of Dr. Wozniak's work focuses on biofilms which are microorganisms that are attached to a surface, play a critical role in infectious diseases. They are innately resistant to antibiotics and often difficult to et rid of. Dr. Wozniak calls the treatment of biofilms a "critically important challenge for anti-infective programs in the pharmaceutical industry."

Dr. Larry Schlesinger visited India in Feb. 2019.

The President and CEO of Texas Biomedical Research Institute, Dr. Larry Schlesinger, is a physician researcher who is a leader in his field – infectious diseases and tuberculosis in particular. He recently traveled to India to visit one of the many places across the globe where TB has a huge impact. The 8th annual RePORT India Joint Leadership Meeting was held in Chennai, India, February 4-6, 2019.

Dr. Jordi Torrelles meets with future collaborators on a 2019 trip to Africa.

Tuberculosis is the deadliest infectious disease in the world: tuberculosis. Somewhere in the world, a person dies of TB every 21 seconds.

Africa is a continent full of supreme beauty. Sadly, it is also a continent facing some intense health crises. Imagine trying to test for TB in areas where there may not be electricity of even running water. One of Texas Biomed’s TB researchers traveled to three countries Africa in early 2019 to create collaborations to help test a cheaper, faster, easier way to detect the disease and pinpoint the best course of treatment.

Many parts of Africa are still wild and home to spectacular animals.

While he was in Mozambique, Swaziland and South Africa, Professor Jordi Torrelles, Ph.D., spent much of his time talking to people at various clinics and research facilities. Working in collaboration with these groups, Dr. Torrelles is planning to have samples from some of the many TB patients in this region processed, frozen and shipped to San Antonio, Texas, so that Texas Biomed researchers can work on an experimental detection system.

TB clinics in the southern part of Africa do what they can with few resources.

Dr. Torrelles' research reaches to many others part of the globe as well, including Guatemala, Panama, El Salvador, Malawi, Democratic Republic of Congo, India, China, Ukraine.

This technology would help clinicians tailor therapies. (Photo courtesy of Josh Parks)

A collaboration of scientists including Texas Biomedical Research Institute’s Professor Jean Patterson, Ph.D., are working on a new way to detect Zika virus that will help guide clinicians in their treatment of patients with the disease. The new technology will screen bodily fluids such as blood, urine or semen, for the presence of the virus. The experimental diagnostic tool will also help pinpoint the stage of the disease in those infected.

Researchers at the University of California at Santa Cruz, Brigham Young University, and the University of California at Berkeley developed the technology that is now being tested to see if it is effective. Electrical engineering Professor Holger Schmidt, Ph.D., of UC Santa Cruz is one of the leading researchers testing the technology, which he describes as “a lab on a chip.”

Texas Biomed’s role in this scientific advancement is to provide knowledge about the virus and viral material to the team of researchers.

“What this technology will do is tell us, first of all, if you’ve already been infected,” Dr. Patterson explained. “If you have antibodies, you wouldn’t be at risk for a new infection. It will also tell us where you are in your infection.”

Knowing the stage of the disease is critical since many antivirals only work early in infections and are not effective later in the course of the disease. This particular diagnostic test would tell clinicians if the patient is showing a sign of recent infection or if the disease has progressed.

The mosquito-borne illness was first identified in Uganda in 1947, but Zika roared into international headlines in 2014 when cases of the virus in Brazil were shown to have a connection to devastating birth defects in babies born to mothers who had Zika while pregnant.

The study into a new diagnostic technology to pinpoint Zika started two years ago. Patterson is confident her work will contribute to more effective diagnostics.

“We’ve got this,” Patterson stated.

The same test is being developed for another pathogen Texas Biomed researches: Ebola virus. Dr. Schmidt is hopeful this technology would be helpful for people in remote areas affected by Ebola, such as parts of Africa.

The collaboration of scientists working on the project have applied for another scientific grant and they plan to apply for a grant to commercialize the experimental Zika test.

Childhood obesity is one of the most pressing public health issues of our time. Now, with the help of a $3 million grant from the National Institutes of Health, Associate Professor Melanie Carless, Ph.D., is using the field of epigenetics to study this nagging problem. Dr. Carless will look at the way DNA, RNA, and proteins are affected by both the environment and genetic makeup to impact the risk of obesity.

Melanie Carless, Ph.D.

Two Texas Biomed researchers are collaborating with Dr. Carless. Associate Professor Tiziano Barberi, Ph.D., is lending his expertise in the development of pluripotent stem cells. Associate Professor Shelley Cole, Ph.D., is helping with the date from the cohort of 900 Texas Hispanic children used in the study.

Raul Bastarrachea, MD, and Jack Kent, Ph.D.

Texas Biomedical Research Institute scientists have been granted funding from the National Institutes of Health to pursue a promising study on the ultimate causes of heart disease and metabolic disorders. Principal Investigators Raul A. Bastarrachea, MD, and Jack W. Kent Jr., Ph.D., of Texas Biomedical Research Institute have designed the GEMM Family Study (Genetics of Metabolic Diseases in Mexico or Genética de las Enfermedades Metabólicas en México).

The GEMM Family Study examines volunteers from 10 university hospital sites in Mexico. Blood samples and tissue samples collected from participants are analyzed at Texas Biomedical Research Institute in San Antonio, Texas.

Healthy adults provide baseline blood samples and muscle biopsies at fasting. Then, they are given what’s called a meal challenge. The volunteers eat 30 percent of what their bodies need for their individual daily energy needs based on their Base Metabolic Rate (BMR) and activity level.

If their metabolism is working correctly, that food – a balanced mix of proteins, carbohydrates, fat and micronutrients – should be metabolized, oxidized, or stored within five hours. By taking another muscle biopsy and blood samples at several points during the five hours following the meal, the researchers hope to find out why some otherwise healthy people may have an impaired response to a meal which can lead to cardiovascular disease over time.

“The idea behind the GEMM Family Study is to pinpoint novel biomarkers of metabolic responses that could be early predictors of cardiovascular disease,” explained Dr. Bastarrachea. Distinguishing those biomarkers could lead to earlier diagnoses and interventions based on individual results.

Heart disease is a major health problem for Hispanic Americans. High rates of obesity, diabetes and high blood pressure put them at great risk for cardiovascular problems like strokes and heart attacks. The scientists anticipate that findings from the GEMM Family Study will have implications for diagnosing and treating cardiovascular disease on both sides of the U.S.-Mexico border.

The National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, has awarded the GEMM Family Study researchers $544,803 over two years to study data from 40 people in Mexico. Using that preliminary data, Texas Biomed scientists plan to apply for a larger NIH grant that would fund the study of data collected from 400 individuals.

Texas Biomed has a long history of researching genetic contributors to heart disease risk in family studies, including ongoing collaboration in the StrongHeart Study of American Indians.

The GEMM Family Study is being supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R56DK114703.

This study will involve collaborative research by scientists at TBRI and UT Health San Antonio. Molecular analyses of gene expression will be conducted by the laboratory of Dr. Shelley Cole and the TBRI Genomics Sequencing Core. Other molecular profiling will be conducted at the UT Health Mass Spectrometry Laboratory under the supervision of Drs. Susan Weintraub and Xianlin Han.

The locations in Mexico where volunteers are taking part in the GEMM Family Study are:

MONTERREY, Facultad de Enfermería, Universidad Autónoma de Nuevo Leon (UANL), Facultad de Salud Pública y Nutrición (Faspyn), UANL, Hospital Metropolitano Monterrey (Dr. Esther Gallegos and Dr. Edna Nava)

MERIDA, Escuela de Ciencias de la Salud de la Universidad Marista de Mérida (Dr. Hugo Laviada and LN Maria Fernanda Molina)

CUERNAVACA, Facultad de Medicina de la Universidad Autónoma del Estado de Morelos (Dr. Jesús Santa-Olalla and and Dr. Jose Ángeles Chimal)

CHIHUAHUA, Facultad de Medicina de la Universidad Autónoma de Chihuahua (Dr. Irene Leal)

MORELIA, Universidad Latina de América, Michoacán (Dr. Juan Carlos Castillo y Dr. Areli Murillo)

GUADALAJARA, Instituto Superior Autónomo de Occidente, A.C., Universidad Católica (UNIVA), Hospital Salud de los Enfermos (Dr. Laura Gonzalez and Dr. Rocio Salinas)

VERACRUZ, Instituto de Investigaciones Medico Biológicas, Universidad Veracruzana (Dr. José Maria Remes)

CIUDAD VICTORIA, Hospital Infantil de Tamaulipas SSA (Dr. Judith Cornejo)

SAN LUIS POTOSI, Facultad de Ciencias Químicas, Universidad Autónoma de SLP (Dr. Claudia Escudero)

MEXICO, Facultad de Ciencias de la Salud Universidad Anáhuac México Norte, CDMX Hospital ISSSTE CDMX “Lopez Mateos” (Dr. Ernesto Rodriguez and Dr. Martha Eunice Rodriguez)

INSTITUTO NACIONAL DE MEDICINA GENOMICA CDMX (Dr. Lorena Orozco, Dr. Angelica Martinez

Samples from nonhuman primates make up the tissue bank at the SNPRC.

In the Hixon Hospital, drawers upon drawers hold thousands of animal tissue samples. Protected in wax, this collection is a valuable resource for Texas Biomed scientists and researchers at other institutions that participate in a tissue sharing program.

Scientists who wrote a recent article published in the Journal of Medical Primatology titled “Papio Spp. Colon microbiome and its link to obesity in pregnancy” used tissue samples from the Southwest National Primate Research Center to test a hypothesis: Are there changes in the kinds of bacteria found in obese animals versus normal weight animals? Could those differences influence the outcome of pregnancy?

Obese women at are increased risk of a number of pregnancy complications including gestational diabetes, preeclampsia, and the need for a cesarean delivery.

Edward Dick, Jr., D.V.M., is a veterinary pathologist at the SNPRC who is one of the authors of the article. He explains “the microbiome is a new research area that’s being studied extensively in humans, but no one had really looked at the baboon to see how it compares to the human. This was the first attempt to do that.”

Edward Dick, Jr., D.V.M.

The colon microbiome is made up of trillions of bacteria, fungi and other microbes. It plays an important role in health, including digestion and immunities.

The SNPRC tissue bank provided samples of gut microbiome from four obese pregnant baboons and four normal weight pregnant baboons.  These were evaluated by researchers from the College of Medicine at the Texas Tech University Health Sciences Center.

When comparing the samples, scientists noted some differences. For instance, the population of one certain bacterium was increased ten-fold in the obese baboons. Antibodies to this particular bacterium have been associated with metabolic disturbances and insulin resistance in people.

On the flip side, two other bacteria used to help ferment carbohydrates and metabolize fatty acids were reduced in the obese baboons.

The question is whether differences in the colon microbiome could make a difference in the outcome of pregnancy. The short answer is that it’s possible. Much more research needs to be conducted.

The study concludes “changes in the gut microbiome in pregnant obese animals open the venue for dietary manipulation in pregnancy.” If this proves to be the case, researchers may be able to come up with a suitable target for microbiome-related intervention during pregnancy.

Thousands of slides are stores in drawers at the SNPRC.

The article also acknowledges “the help and dedication of the many excellent animal caretakers, technicians, and veterinarians of the Southwest National Primate Research Center.”

Obesity is a public health concern in the U.S. and around the world. Since the children of obese mothers have a risk of future obesity and heart disease, this kind of research into underlying factors that might be controlled during pregnancy is important.

Dr. Dick says this collaborative research project is a good example of the power of banked tissue for biomedical research. The SNPRC has samples with records on diagnoses that go all the way back to 1988.

Dr. Schlabritz-Lutsevich (Associate Professor at Texas Tech University Health Sciences Center at the Permian Basin) is the Principal Investigator, senior and corresponding author on this study.  Study was funded by UTHSCSA, UTHSC and TTUHSC. Dr. Schlabritz-Lutsevich worked closely with the group of Dr. Peter Nathanielsz, who provided continuous support. She assembled the interdisciplinary team, which included Dr. Karen Nelson – the first scientists, who published first microbiome study in 2006, Dr. Christopher Rensing – University of Denmark (in addition to other authors). The help of Dept. of Pathology SNPRC was critical for this research, especially Dr. Edward Dick and Dr. Gene Hubbard.

Dr. Franco Folli is now Professor of Endocrinology, University of Milan, Italy.

Macaques are used for Ebola research.© Clem Spalding 210-271-7273

When you hear the phrase “natural history” – what comes to mind? A display at a museum? A college course? At Texas Biomed, natural history means a certain kind of study that tracks the course of an infectious disease

Associate Scientist Ricardo Carrion, Jr., Ph.D., serves as the Director of Maximum Containment Contract Research. He explains that documenting the course of a disease -- in this case, Ebola virus --in a nonhuman primate helps make sure the monkey is a good and accurate model.

Ricardo Carrion, Jr., Ph.D.

The FDA will use these animal models to evaluate experimental Ebola vaccines and therapeutics that come through the pipeline. The federal government characterizes Ebola as a high priority threat. That’s why money is being invested – to protect people – with either a vaccine or a therapeutic if the virus happened to come into the United States, as it did in 2014 when two nurses in Dallas contracted the disease from a patient with Ebola who traveled here from Africa. While most people in America don’t see Ebola as a threat, there is a chance the virus could be weaponized for a bioterrorism attack…or it could show up again in a visitor arriving from another country.

Texas Biomed competed for -- and won -- the grant to conduct these natural history studies, in part, because of its long and successful history working with high containment pathogens.