Aging-Related Neurodegeneration

Many Barshop faculty members are investigating the biology underlying brain aging and age-related neurodegenerative disorders. Our highly collaborative group of faculty with expertise in the aging brain span from basic science to clinical research. Many of our faculty also share appointments with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, the Perry and Ruby Stevens Parkinson’s Disease Center of Excellence, and the Center for Biomedical Neuroscience, as well as academic appointments with various UTHSA departments.

Alzheimer’s disease and related tauopathies. The Barshop is home to a Functional Lipidomics Core, directed by Dr. Xianlin Han, who also directs the South Texas Alzheimer’s Center Biomarkers Core. Dr. Han’s group has a special interest in sulfatides, a class of myelin-specific lipids, and the consequences of sulfatide deficiency in aging and the development of Alzheimer’s disease. Dr. Juan Pablo “JP” Palavicini’s research team is also interested in lipids, with an emphasis on ceramide-induced lipotoxicity in the context of brain aging and Alzheimer’s disease.

The laboratory led by Dr. Bess Frost studies how aging and tau-induced aberrations in the nucleus, including heterochromatin decondensation, retrotransposon activation and alterations in RNA metabolism, contribute to neuronal death and neuroinflammation using Drosophila melanogaster, tau transgenic mice, human cell cultures and human brain. Dr. Sarah Hopp’s laboratory also studies tauopathy – particularly the role of microglia, the immune cells of the brain, as a clearance mechanism for pathological forms of tau. They are working to determine how microglia contribute to the initiation and progression of tau-related neurodegeneration and cognitive decline.

Several Barshop investigators focus their efforts on the role of mitochondria and oxidative stress in Alzheimer’s disease. Dr. Roger Shi’s laboratory studies ALCAT1 and the mitochondrial etiology of aging and age-related disorders, including Alzheimer’s disease. Studies led by Dr. Qitao Ran investigate the key cellular events triggered by reactive oxygen species that drive neuronal injury and death. A particular emphasis is on links between reactive oxygen species and ferroptosis in Alzheimer’s disease and amyotrophic lateral sclerosis.

Traumatic brain and spinal cord injury. Dr. Lizhen Chen’s group is focused on genetic and epigenetic regulation of neuronal aging and age-dependent axon regeneration. Dr. Chen’s laboratory integrates studies using the genetically tractable roundworm C. elegans with work in mice and human cell cultures.

Dr. Jim Lechleiter, director of the UTHSA Optical Imaging Facility, leads a team that is actively investigating the role of astrocytes in the context of brain injuries, and how astrocytes may be leveraged for neuroprotection. Dr. Lechleiter has co-founded a company, Astrocyte Pharmaceuticals, based on the discoveries in his laboratory.

Dr. Naomi Sayre’s team seeks to understand the basic biology underlying brain recovery after stroke or traumatic brain injury. Ongoing studies are focused on the role of cholesterol metabolism, ApoE status, and LRP1 in recovery after brain damage.

Dr. Kevin Bieniek, director of the Glenn Biggs Brain Bank, focuses on the role of traumatic brain injury in the etiology and progression of neurodegenerative disorders and physiological aging by combining traditional pathological analysis with new state-of-the-art technologies for analyzing postmortem human brain tissue.

Parkinson’s disease. Dr. Randy Strong, director of the Barshop NIA Aging Interventions Testing Program and the UTHSA Nathan Shock Center of Excellence in the Biology of Aging, leads a research team focused on neurotransmitters, neurotransmitter receptors, and intracellular signaling pathways in the context of Parkinson’s disease. Within Dr. Strong’s group, Dr. Elizabeth Fernandez focuses on aldehyde dehydrogenase 1a1 and glutamate peroxidase 1 in Parkinson’s disease, and whether use of aldehyde trapping agents suppresses Parkinson-like symptoms in mice.

The laboratory directed by Dr. Andrea Giuffrida, UTHSA Vice President for Strategic Industry Ventures, is interested in the endocannabinoid system as a regulator of motor function. In addition to studies in mouse models of neurological and psychiatric disorders, the team investigates new pharmacotherapies in patients with Parkinson disease.

Human studies. Dr. Jamie Walker, co-Director of Biggs Brain Bank, studies brains of “superagers,” individuals who are resistant or resilient to the neuropathologic changes that commonly occur over the course of aging. Overall, her research program seeks to identify mechanisms of prevention that will lead to novel interventions for Alzheimer’s disease and related dementias.

Dr. Sudha Seshadri is a neurologist and the founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, an NIH-designated Alzheimer’s Disease Research Center. Scientifically, Dr. Seshadri’s research group utilizes population neuroscience to identify risk factors associated with neurodegenerative disorders. Through this work, they seek to identify cellular pathways that drive dementia, and integrate genetic, blood-based, clinical and imaging biomarkers to determine disease risk and understand disease heterogeneity.

Dr. Peter Fox leads the UTHSA Research Imaging Institute, which enables our study teams to visualize brains of living animals, including humans, via magnetic resonance imaging (MRI) and positron emission tomography (PET). Dr. Fox’ group works to develop computational tools and resources that enable quantitative meta-analyses and co-activation mapping and functional decoding of neuroimaging data.

Dr. Don Royall is a neuropsychiatrist interested in cognitive performance in the context of general intelligence and successful aging. His early work resulted in the Clock Drawing Test (CLOX), a nonverbal screening assessment that is commonly used to quantify cognitive function.

Ongoing clinical trials in the area of Alzheimer’s disease include ART-AD (Barshop investigators Dr. Bess Frost, Dr. Nick Musi, Biggs investigator Dr. Campbell Sullivan) and PREVENTABLE (Barshop investigators Dr. Nick Musi and Dr. Sara Espinoza). Additional opportunities for clinical trials in the area of Alzheimer’s disease are available through the Biggs Institute.

Brain networks and cellular crosstalk. Dr. David Morilak, director of the Center for Biomedical Neuroscience, studies stress-related psychiatric disorders and the negative impact of stress. His team focuses on the structural, functional and regulatory changes in prefrontal circuits that underlie neuronal plasticity. Recent work is focused on investigation the causes of cognitive decline after cancer therapy.

The laboratory directed by Dr. Martin Paukert studies interactions between neurons and astrocytes in the context of neuromodulation. His team utilizes in vivo calcium imaging to understand the molecular events and behavioral contexts that facilitate neuron-astroglia interaction in neurodegenerative and neurobehavioral disorders.

Dr. Jason O’Connor’s research group is focused on understanding the biological basis of inflammation-related depressive disorders. They utilize mouse models of inflammation-induced depressive behavior to investigate how the kynurenine pathway control neuroimmune interactions and effects behavioral changes.