Unlocking the Mysteries of the Brain

UTSA’s Brain Health Consortium is developing precision brain therapies to transform patients’ lives

By Daniel Lockerbie

The brain is one of the most fascinating organs in the human body. It is also the most complex, able to perform a seemingly endless number of functions and abilities, all while storing a vast amount of information. But this multifaceted organ is prone to a number of diseases, many of them unexplainable and incurable. What if a genetic diagnosis was the first step toward a cure?

Cindy Peterson is a 45-year-old woman who exercises regularly and has a healthy diet. So it was a shock when Peterson had a heart attack a year ago. She was diagnosed with arrhythmogenic right ventricular hypertrophy, which means the muscle tissue in the right ventricle dies and is replaced with scar tissue. This disrupts the heart’s electrical signals and causes the heart to beat irregularly. The treatments for this condition, however, just work short-term, and the only long-term option is for Peterson to receive a heart transplant. Peterson went to see a genetic counselor and found out she has a mutation in a crucial mitochondrial gene that makes energy for the heart and regulates how it beats. Peterson has two children, a 13-year-old son and a 17-year-old daughter, and genetic sequencing revealed that both of her children have the same cardiac gene mutation. Peterson’s daughter is already showing similar symptoms.

Illustrations: MimiPrints. All rights reserved.

In 2012, scientists invented a technology that makes changes to DNA in cells—and holds the potential to create positive endings for stories like Peterson’s. This technology, called CRISPR gene editing, could one day fix mutations that cause a number of genetic diseases. In the future, some genetic diseases maybe be able to be cured as soon as a diagnosis is made. Therapies such as CRISPR are developed as a “disease-in-adish,” a model that recreates the development of human disorders using a patient’s stem cells. Drugs are first tested in these cellular models, then tested in animals, and finally tested in clinical trials. Using CRISPR and other technologies, UTSA’s Brain Health Consortium (BHC)—recently approved as an organized research unit under the Vice President for Research, Economic Development, and Knowledge Enterprise—is already making progress toward a future where the diagnosis of a genetic disease is not a dead end, but instead the first step toward a cure. Researchers at UTSA’s Brain Health Consortium contribute their expertise—in neurodegenerative disease, brain circuitry, traumatic brain injury, regenerative medicine, drug design and psychology—to large-scale research projects that seek to produce a greater understanding of the complex workings of the brain and the factors that lead to its decline. The consortium focuses on four research areas: neurodegenerative disorders (Alzheimer’s and Parkinson’s disease), neurodevelopmental disorders (epilepsy, autism), neuropsychiatric disorders (bipolar disorder, addiction) and traumatic brain injury. Led by director Dr. Jenny Hsieh, professor of biology and the Semmes Foundation Chair in Cell Biology, the UTSA Brain Health Consortium plays a pivotal role in furthering our understanding of the brain. “UTSA has made a bold effort to become a leader in brain health-related research, and innovative technologies such as CRISPR, multi-omics analysis and human induced pluripotent stem cells add to our capabilities,” says Hsieh. “This is an exciting time for undergraduate and graduate students to get involved in cutting-edge laboratory research. There’s a great need in the workforce for individuals with scientific intellect and possessing both wet lab and computational skillsets.” Currently, BHC membership is being established to encompass a broad spectrum of disciplines, from engineering to education to biology. One member, Dr. George Perry, professor of biology and the Semmes Distinguished Chair in Neurobiology at UTSA, has conducted Alzheimer’s research for nearly 40 years. Perry says “the consortium provides a broader base of expertise,” a valuable advantage he believes benefits his research. Dr. Melanie Carless, an associate professor in the Department of Biology, recently joined the consortium. She provides expertise in defining the genetic basis of brain health and furthering the understanding of the biology behind neurological and psychiatric disorders. “One of the most striking aspects of this consortium is the welcoming and collaborative spirit of all members,” she says. “Since arriving, I have been involved in developing several new project ideas with other investigators that really push the boundaries of interdisciplinary research. Efforts such as this will contribute to UTSA’s mission to advance knowledge through research, discovery and teaching, as well as promote its vision to be a premier

public research university.”

The consortium also offers courses and opportunities for students looking to further their research, such as Kaisha Meyer, who is a second-year neurobiology Ph.D. student in Hsieh’s lab. “BHC is collaborative and spans several different fields with the common goal of tackling the complexities of the brain in health and disease,” says Meyer, who is studying genetic risk variants for Alzheimer’s disease. “In most of science, you become focused on a small aspect of human disease and you become an expert in that. However, in complex brain diseases, it is essential to understand the whole picture of what is going on to make effective drugs to treat patients. As a student, being a part of a collaborative effort reminds us how collaboration is key to making real progress.” Meyer is particularly encouraged by the consortium’s approach to collaboration in the name of furthering research. “I think that mentality of collaboration instead of isolation is something we can take with us into our own labs and future career paths,” she says. “It’s exciting to be involved in a consortium of scientists with different backgrounds coming together to solve a common problem.”

For more information about the Brain Health Consortium, please visit utsa.edu/bhc.