The William and Ella Owens Medical Research Foundation recently awarded $1.5 million to The University of Texas Health Science Center at San Antonio (UT Health San Antonio) for research projects that address pancreatic cancer, Alzheimer’s disease and childhood cancers.
This year, the foundation will fund $250,000 each to six research projects from UT Health San Antonio investigators. This year’s recipients, along with their project titles and synopses, are:
Sijia He, PhD, assistant professor of research in the Department of Cellular and Integrative Physiology and member of the Sam and Ann Barshop Institute for Longevity and Aging Studies
Project: Interrogating the innate immune-myelin communication in Alzheimer’s disease
Synopsis: Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive memory loss and cognitive decline. While much AD research has focused on amyloid plaques and tau tangles, emerging evidence points to another critical disease promoting factor: Damage to myelin, the protective sheath surrounding nerve fibers that enables efficient communication between brain cells.
This project aims to study how myelin damage interacts with microglia, the brain’s immune cells, and how this relationship contributes to the progression of Alzheimer’s. Using multiple mouse models that represent distinct forms of myelin injury, we will investigate how these changes trigger microglial responses and how microglial innate immune activity, in turn, influence myelin health.
A special focus will be placed on the cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway, which plays a central role in regulating immune responses in the brain and has been identified by our team as a key factor in AD progression.
By examining the connection between myelin integrity and immune regulation, this research has the potential to reshape our understanding of AD and opens the door to innovative therapeutic strategies that could improve the lives of millions.
Jean Jiang, PhD, professor and Zachry Distinguished University Chair in the Department of Biochemistry and Structural Biology (Co-PI: Chu Chen, PhD, professor in the Department of Cellular and Integrative Physiology)
Project: Inhibiting astrocyte connexin hemichannels to treat Alzheimer’s disease
Synopsis: Alzheimer’s disease and related dementias, or AD/ADRD, characterized by progressive memory loss, behavioral changes and personality abnormalities, are the leading causes of dementia in individuals age 65 and older. Currently, approximately 6.7 million people in the United States age 65 or older live with Alzheimer’s disease.
While current medications can temporarily improve symptoms or slow progression in the early stages, there are no effective treatments or cures available for AD/ADRD. Most approved drugs and ongoing drug development programs target well-known disease mechanisms, such as amyloid precursor protein, which leads to the formation of amyloid beta (Aβ) plaques, one of the pathological features of AD.
In this proposal, researchers aim to investigate a novel therapeutic target: Connexin 43 (Cx43) hemichannels on astrocytes, supportive brain cells essential for neuronal health. In Alzheimer’s disease (AD), Aβ accumulation triggers the opening of these hemichannels, releasing harmful molecules that drive neuroinflammation and neuronal loss. We have developed a specific antibody that blocks Cx43 hemichannels. Preliminary data suggest it improves cognition, reduces inflammation and lowers Aβ plaques in animal models. We will test its efficacy and mechanism in AD models using behavioral, biochemical and histological methods.
Naomi Sayre, PhD, assistant professor in the Department of Neurosurgery (Co-PI: Erzsebet Kokovay, PhD; associate professor, Department of Cell Systems and Anatomy)
Project: Regulation of death and Alzheimer’s disease susceptibility in adult-born hippocampal neurons by LRP1
Synopsis: In Greek mythology, Mnemosyne is the Titan goddess of memory. The idea of memory as Titan likely stems from our cultural understanding of how memory helps form the core of a person’s personality, experience and perspective. This is also one reason that loss of memory can be so devastating – it is especially prevalent amongst people who suffer from Alzheimer’s disease and other dementias; this neurodegenerative disease strips people of much of what they were. We have discovered a new player in the brain’s ability to retain memory: The protein LRP1 (low-density lipoprotein receptor related protein). We think understanding LRP1 will lead to exciting and novel insights into how patients with Alzheimer’s disease lose their memory. This is particularly important given that Alzheimer’s disease and related dementias are expected to triple in incidence over the next 40 years as our population ages.
The goal of this study is to understand how LRP1 influences the abnormal development of neurons from neural stem cells and, importantly, to test whether increasing LRP1 activity can reduce negative outcomes in Alzheimer’s disease models. Researchers expect the results of this study will lay a strong foundation for large-scale investigations that could improve the likelihood of treating patients with Alzheimer’s disease by targeting neural stem cells and improving memory.
Simon Gayther, PhD, professor in the Division of Hematology and Oncology; founding director, Center for Inherited Oncogenesis (Co-PI: Patrick Sung, DPhil; professor in the Department of Biochemistry and Structural Biology and Robert A. Welch Distinguished Chair in Chemistry)
Project: Drug targeting in early-stage models of pancreatic cancer
Synopsis: Five-year survival rates for pancreatic ductal adenocarcinoma, PDAC, are the worst of all tumor types. Globally, the incidence of the disease is rising. In South Texas, PDAC represents a major cancer burden. During 2011-2015, PDAC incidence was 12.3 per 100,000, higher than the national average.
One main barrier to effective prevention and treatment is the difficulty in modeling PDAC. Its underlying pathology remains poorly understood at the mechanistic level. In our laboratories, we have established innovative methods to understand the early stages of PDAC development.
In Aim 1, researchers will establish induced pluripotent stem cell (iPSC) models of normal pancreatic tissues with and without BRCA2 mutations, the strongest known genetic risk factor for PDAC. To these iPSC models, we layer on additional mutations frequently occurring in PDAC, namely mutations in the KRAS, TP53, CDKN2A and SMAD4 genes. This allows researchers to mimic both the early and later stages of PDAC to identify precision therapies that could improve outcomes.
Researchers have also developed spatial multi-omics profiling, another innovative technology, which helps clarify the cellular origins of PDAC. This approach may lead to novel clinical biomarkers for early detection and treatment.
In Aim 2, researchers will examine functional interactions between BRCA2 and mutated versions of KRAS, TP53, CDKN2A and SMAD4 in the iPSC models. They will study how these interactions affect the DNA damage response, specifically DNA damage repair and replication fork preservation. The goal is to define how BRCA2 physically and functionally interacts with the co-occurring mutations in KRAS, TP53, CDKN2A and SMAD4 to impair DNA damage repair and replication functions of BRCA2.
Gang Huang, PhD, professor in the Departments of Cell Systems and Anatomy and Pathology and Laboratory Medicine; holder of the Kathryn Mays Johnson Distinguished Chair in Oncology; associated with UT Health San Antonio’s Mays Cancer Center
Project: The role of the Warburg effect on cellular and systemic energy metabolism in PDAC cachexia
Synopsis: Pancreatic ductal adenocarcinoma, or PDAC, is one of the deadliest types of cancer and is often diagnosed in its later stages. A common and very serious problem that the majority of PDAC patients face is called cancer-associated cachexia, or CAC—a profound weight loss and muscle wasting condition that not only weakens patients but also makes treatments less effective. CAC-induced organ failure is the primary cause of death in patients with advanced cancer, and unfortunately, there are no FDA-approved treatments for the condition.
This project investigates how the loss of a key regulator gene, called LKB1 or STK11, in PDAC cells leads to a chain reaction in the body’s energy use, known as the Warburg effect. In healthy cells, LKB1 helps maintain balanced energy production by activating AMPK. When LKB1 is missing, cancer cells accelerate their sugar-burning processes (glycolysis), while reducing fat-burning processes like fatty acid oxidation and other energy-generating pathways. This shift forces the tumor to use up large amounts of glucose, lowering blood sugar levels throughout the body. As a result, the patient’s muscles and fat stores are broken down to compensate, contributing to the severe weight loss seen in cachexia. Eventually, this unintentional weight loss leads to weakness, fatigue, anorexia, pain, depression and systemic organ failure.
By pinpointing the exact molecular events that drive this imbalance in both cells and animal models, researchers aim to develop new therapies that block the tumor’s hijacking of the body’s energy stores.
Mingjiang Xu, PhD, professor in the Department of Molecular Medicine and CTRC Council Distinguished Chair in Oncology; associated with UT Health San Antonio’s Mays Cancer Center (Co-PI: Yaxia Yuan, PhD, assistant professor in the Department of Biochemistry and Structural Biology)
Project: Develop PSPC1 degrader for novel pediatric AML therapeutics
Synopsis: The most common pediatric cancer is acute leukemia, of which acute myeloid leukemia, or AML, accounts for about 20% of cases. The current treatment approaches for pediatric AML primarily rely on intensive chemotherapy, followed by stem cell transplantation for high-risk or relapsing patients. While there have been some recent successes with genetically targeted therapies for adults, pediatric AML has been slower to advance in children due to its distinct genetic features. Therefore, it is crucial to discover common dependencies for both pediatric and adult AMLs, despite their diverse genetic drivers. Targeted therapies based on such common dependency could offer a “one-size-fits-all” therapy, especially pediatric AMLs with distinct genetic features.
Our recent studies (published in Cell Stem Cell, 2025) have discovered paraspeckle protein component 1 (PSPC1) as a novel pan-AML target. PSPC1 is a protein implicated in the development and spread of multiple solid cancers. Preliminary screening has identified a few small molecules that can induce rapid PSPC1 degradation in AML cells. These compounds exhibit potent anti-leukemic activity, while having minimal effect on normal cells. In this project, we will optimize our PSPC1 small molecule degraders in a timely and cost-effective manner. We will then perform validation of the best degrader by evaluating its specificity, anti-leukemic potency and toxicity. Our study could lead to breakthrough in AML treatment by developing novel PSPC1 small molecule degraders as a safe and effective therapeutics for pan-AMLs, especially pediatric AMLs.
This project will continue to be synergized with the collaboration of Drs. Xu and Yuan, who bring complementary expertise in AML research, target identification and computer-/AI-guided drug discovery. The team aims to develop PSPC1 degraders, a small molecule that could have broad applications for cancer treatment far beyond pediatric and adult AMLs.