Texas Biomedical Forum Announces 2017 Grant Recipients

The Texas Biomedical Forum is an independent, non-profit association dedicated to promoting the life-saving work of Texas Biomed. The Forum sponsors one-year pilot projects that help scientists prove concepts that can lead to subsequent and often significant federal funding of research. In the last thirteen years alone, the results of funded studies have led to additional grants amounting to an estimated $55 million.

This year, the Forum provided more than $400,000 worth of grant monies to scientists at Texas Biomed, and thanks to support from the Douglass Foundation, the Forum was able to offer grants to two graduate students, as well. The 2017 Forum grant recipients in the scientist, postdoctoral scientist and graduate student categories are:

Scientists

Eusondia Arnett, Ph.D.

Eusondia ArnettEffect of HIV infection on M.tuberculosis granuloma formation and evolution

People living with HIV are 30 times more likely to develop active TB than those without TB. Dr. Arnett seeks a clearer picture of the body’s immune response during co-infection. This project will use a novel model to study the lesions in the lungs of tuberculosis patients — called granulomas – and determine whether HIV drastically alters their formation and the body’s immune response to the bacteria which can cause TB.

Abul Azad, Ph.D.

Abul AzadIn vivo efficacy of small molecule anti-TB compounds

Drug-resistant strains of tuberculosis are on the rise, making the fight against the disease more difficult. Dr. Azad’s research targets the discovery and development of novel anti-TB drugs. His team will be testing molecules from a new class of compounds – which were developed for other purposes — in mouse models to see if these drug candidates are active against susceptible strains of TB as well as those with different resistance profiles.

Alberto Muniz, Ph.D.

Alberto MunizBaboon Pluripotent Stem Cell Derived Retina Progenitor Cells for Treatment of Retina Degeneration

Diseases like age-related macular degeneration and retinitis Pigmentosa are a leading cause of blindness. Previous studies in rodents showed that transplantation of specialized cells into the retina can preserve vision. Dr. Muniz wants to expand on that research using non-human primates, specifically baboons. The implanted cells will be labeled with a fluorescent marker so scientists can visually track how their experiment is progressing.

Olena Shtanko, Ph.D.

Olena ShtankoRegulation of VPS34 complex in macropinocytosis

Ebola hemorraghic fever is a sever, often fatal, human disease with no approved therapeutics. The diseases is caused by a virus that gains access into cells using a process called micropinocytosis, a process in which a large fluid-filled sac is pinched off from the cell membrane and brought into the interior of the cell. Using human cultures, Dr. Shtanko will be studying how this process is regulated in cells important for disease progression. The ultimate goal of the project is to find a way to inhibit micropinocytosis and therefore block virus infection.

Jordi Torrelles, Ph.D.

Jordi TorrellesInfluence of the human lung mucosa in Mycobacterium tuberculosis pathogenesis

The respiratory disease tuberculosis kills one person every 21 seconds. Dr. Torrelles’ research focuses on the lung mucosa (lining of the inside) and how that internal environment impacts the control of propagation of the bacterium that can cause a TB infection. Using both donated human lung samples and mouse models, Dr. Torrelles’ aim is to determine what lung biomarkers may determine which people are more likely to become infected with TB, with the ultimate goal of finding new ways to intervene.

Joanne Turner, Ph.D.

Joanne TurnerPredicting Time Since Mtb Infection

Science has no good way to determine when someone was infected with M. tuberculosis or Mtb. That lack of knowledge is a roadblock to developing improved diagnosis or treatment of the disease TB, as well as a better understanding of the disease in humans. Dr. Turner’s research goal is to develop a genomic methodology to predict how long patients were infected with Mtb. Her lab work will focus on a proof of concept using an established mouse model.

Post-doctoral scientist

Bianca Borchin, Ph.D.

Bianca BorchinIn vivo engraftment of hPSC-derived muscle progenitors maintained in long-term cultures

Human pluripotent stem cells (hPSCs) are primitive cells capable of producing any cell of any tissue in the body. However, propagating muscle cell precursors in the lab has been largely unsuccessful. Dr. Borchin is researching ways to establish a better culture system to extend the life span of these important in vivo models. By transplanting these cells into a mouse model, Dr. Borchin will focus on ways the cells might someday be used as therapy for muscle wasting and atrophy that can results from medical conditions and trauma.

Graduate Students (supported by the Douglass Foundation)

Becky Bricker

Becky BrickerSignaling factors that induce ocular lens and olfactory cell types from stem cells

Bricker’s research focuses on answering questions that could lead to the development of stem-cell based therapies for diseases of the eye and olfactory tissues. Her long-term goal is to treat age-related deterioration of tissues. Bricker says the dream would be to develop cell-based therapies to treat complications like cataracts. In the lab, she will be studying the mechanism that makes stem cells become other cells — specifically for the ocular lens and the olfactory system.

Colwyn Headley

Colwyn HeadleyMitochondrial Dysfunction & Aging Adaptive Immunity in Mtb Infection

Tuberculosis is a major global health issue affecting as many as one in four people worldwide. As people get older, they are more susceptible to infection. Headley is investigating the hypothesis that chronic low grade inflammation associated with age may be at the heart of increased susceptibility to TB infection in old age. Using young and old mice, the lab will study how mitochondrial dysfunction impacts susceptibility, and whether any treatments might improve immunities of the elderly against TB and in general.

News Release: Promising New Drug for Hepatitis B Tested First at Texas Biomedical Research Institute’s National Primate Research Center in San Antonio

For Immediate Release

Robert Lanford
Robert Lanford, Ph.D., Director of SNPRC in his laboratory.

San Antonio, Texas (November 7, 2017) – Research at the Southwest National Primate Research Center (SNPRC) on the campus of Texas Biomedical Research Institute helped advance a new treatment now in human trials for chronic hepatitis B virus (HBV) infection. Testing at SNPRC provided proof this novel therapeutic approach and drug delivery mechanism would be safe and effective, as recently published in the international journal Science Translational Medicine.

The World Health Organization characterizes hepatitis B as a major global health problem. An estimated 250 to 400 million people are chronically infected with the virus. More than 800,000 people a year die from complications of cirrhosis of the liver and liver cancer. A vaccine that is 95% effective in preventing hepatitis B infections has been available since 1982, but there is currently no cure for the millions already chronically infected.

The novel therapy by Arrowhead Pharmaceuticals uses a mechanism called RNA interference to reduce the surface antigens created by chronic HBV infections. Surface antigens (called HBsAg) are small molecules involved in virus entry into liver cells. In chronic infection, they may prevent the immune response from clearing the virus. For example, a high level of HBsAg can lead to a greater risk of long-term, chronic infection with hepatitis B and life-threatening complications like cirrhosis and liver cancer. In this setting, reducing HBsAg by RNA interference will have beneficial effects.

Much of the groundbreaking work lies in the technology Arrowhead developed for delivering this small interfering RNA precisely to the liver. Experiments involving chimpanzees at the SNPRC from 2013-2015 provided the proof that this technology works and is safe for humans, laying the groundwork for the patient clinical trials that have followed. Trials of targeted HBV intervention in non-human primates showed the experimental drug was safe and effective enough to be tested in people.

The Director of the SNPRC, Robert Lanford, Ph.D., explained this novel treatment — in combination with conventional HBV therapy — could empower the immune system to kill the HBV-infected cells and potentially cure people of the disease.

“We now have a drug that can knock down hepatitis B surface antigen and determine whether or not we can actually cure people with that,” Dr. Lanford said.

The drug is delivered by subcutaneous (under the skin) injection. Scientists designed a molecule that delivers the medicine directly to the liver where it binds to a receptor. Then, another molecule that’s derived from bee venom, helps break through membranes in the liver cells to deliver the medicine directly into the cytoplasm of the cells where it takes effect. The siRNA interferes with the expression of the HBV messenger RNA that produces the surface antigen.

“The idea is if you could knock the levels of surface antigens down far enough, the immune system would kick back in,” Dr. Lanford said. “This technology is pretty specific for the liver right now, but there are a lot of problems in the liver that you can fix with this besides hepatitis B.”

This kind of targeted therapy may someday be used to develop drugs for other chronic liver conditions like a genetic disorder called Alpha-1 antitrypsin deficiency, caused by mutated inherited genes, which can cause cancer.

The paper outlining the phase two clinical trials in people and the previous studies involving non-human primates was published in the September 27, 2017 edition of the journal Science Translational Medicine, an interdisciplinary medical journal established by the American Association for the Advancement of Science.

Although the SNPRC no longer uses chimpanzees for biomedical research, studies conducted with these non-human primates over decades continue to yield significant scientific information that will advance human health.

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Texas Biomed, formerly the Southwest Foundation for Biomedical Research, is one of the world’s leading independent biomedical research institutions dedicated to advancing health worldwide through innovative biomedical research. The Institute is home to the Southwest National Primate Research Center (SNPRC) and provides broad services in primate research. SNPRC contributes to a national network of National Primate Research Centers (NPRCs) with specialized technologies, capabilities and primate resources, many of which are unique to the SNPRC. The Center also serves investigators around the globe with research and technical procedures for collaborative projects. For more information on Texas Biomed, go to www.TxBiomed.org or for more information on SNPRC, visit www.SNPRC.org.

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit www.arrowheadpharma.com.

Texas Biomed scientist discusses weight gain in America with HealthDay

Dr. Anthony Comuzzie speaks with HealthDay about new CDC report

Anthony G. Comuzzie
Dr. Anthony Comuzzie

Americans now weigh an average of 15 pounds more than 20 years ago, according to a new Centers for Disease Control and Prevention’s National Center for Health Statistics report. As an expert in obesity research, Texas Biomed Scientist Dr. Anthony Comuzzie spoke with several media outlets this week, including HealthDay, to shed some light on the report. The story has been picked up by CBS News and locally on KSAT-12 news.

Dr. Comuzzie is co-director of the TOPS Nutrition and Obesity Research Center. The TOPS Research Center recently launched a study in partnership with Wisconsin-based TOPS Club Inc.® (Take Off Pounds Sensibly®), to understand why some people gain weight – and cannot lose it – while others have success at taking weight off and keeping it off.

Through an electronic questionnaire, volunteers provide eating habits, daily routines, and a history of weight gain and loss. Some volunteers are invited to participate further in the study. For more information on the research study, visit our TOPS Research Center web page.

San Antonio Family Supports Cystinosis Research

Impacted by cystonosis, local family supports long-term research

Azar family with scientists in Genetics

Kim Azar (back left) and her children Ava and John Ben visit Texas Biomed and meet with scientists Dr. Michael Proffitt (left) and Katie Freed (back right) in the Department of Genetics who are working on cystonosis, a rare genetic disorder that both the Azar children have. Cystinosis causes various organs of the body to crystallize and accumulate an amino acid called, cystine. Without treatment, kidney failure can result at a very young age. Dr. Freed and Dr. Proffitt are working to identify genetic factors influencing the cause and development of cystonosis. Kim recently talked with SA Woman magazine about her family’s journey and their support of Texas Biomed. Read more at SA Woman.

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HIV – Defense in Depth: Texas Biomedical Research Institute scientist creates a defense-in-depth strategy for HIV vaccine development

Texas Biomedical Research Institute scientist creates a defense-in-depth strategy for HIV vaccine development

Claiming more than 34 million lives, the AIDS epidemic is the third worst disease outbreak in human history preceded only by the Black Death in the 14th century and Spanish Flu in 1918. thanks to decades of research, HIV/AIDS is no longer a death sentence, but both a vaccine and a cure allude researchers.

Dr. Ruth Ruprecht, Scientist and Director of Texas Biomed’s AIDS program, recently penned an article for Pan European Networks Science & Technology magazine that highlights her lab’s vaccine development strategy. Her defense-in-depth strategy aims to create a three-pronged approach to defeat the HIV virus that causes AIDS at multiple levels, including the mucosal barriers, mucosal tissue and in the circulation system throughout the body.