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Oscar Alcoreza's Dissertation Defense (5/3/2021): Modulating System xc- Activity As A Treatment For Epilepsy

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Oscar Alcoreza

Dissertation Defense: Modulating System xc- Activity As A Treatment For Epilepsy

Oscar Alcoreza

Graduate Student, Virginia Tech Translational Biology, Medicine, and Health
Graduate Research Assistant, Sontheimer Lab, Fralin Biomedical Research Institute at VTC
Medical Student, Virginia Tech Carilion School of Medicine '23

May 3, 2021 at 8:00 a.m.

About this Dissertation

Epilepsy, characterized by unpredictable seizures, affects approximately 2.2 million Americans, with 150,000 new cases being diagnosed each year. Seizures typically occur when there is an imbalance between the excitatory and inhibitory processes in the brain. Because neurons are the primary cell in the brain that carry out these processes, clinically used anti-epileptic drugs (AEDs) work by either decreasing neuronal excitation or increasing neuronal inhibition. Despite success with managing seizures, up to 1-in-3 patients with epilepsy do not find any relief with existing AEDs. A statistic that has not changed in over 50 years of drug development. With this in mind, the overarching goal of Alcoreza's project is to broaden the search for new AED targets by further characterizing a unique mouse model of epilepsy and exploring the efficacy of targeting non-neuronal processes to treat epilepsy. One such target studied in Alcoreza's research in the Sontheimer Lab is system xc- (SXC), a glutamate/cystine antiporter present on astrocytes, a non-neuronal cell that provides maintenance, support and protection for neurons. Investigations in tumor-associated epilepsy from the Sontheimer lab revealed that hyperactivity of SXC in tumor cells was directly related to the development of tumor-associated epilepsy. These studies also revealed that SXC inhibition using sulfasalazine (SAS), an FDA approved drug, can decrease seizure burden in a tumor mouse model. Therefore, the principal objective of this study is to further investigate the role of astrocytic SXC activity in the development of epilepsy and seizure generation. Alcoreza's research shows that SXC inhibition, using SAS, is able to decrease neuronal hyperactivity and decreases seizure burden in an astrogliosis-mediated epilepsy model.

More About the Candidate and Project

Education

Virginia Tech Carilion School of Medicine, M.D. Candidate

Virginia Tech Translational Biology, Medicine, and Health, Ph.D. Candidate

Boston University School of Medicine, M.S., Medical Sciences

College of William and Mary, B.S., Biology

 

Training

Graduate Research Assistant, Sontheimer Lab and Center for Glial Biology in Health, Disease, and Cancer

 

Mentor

Harold Sontheimer, Ph.D.Adjunct Professor, Fralin Biomedical Research Institute at VTC

Committee Members

  • Susan Campell, Ph.D., Assistant Professor, Department of Animal and Poultry Sciences, College of Agriculture and Life Sciences, Virginia Tech
  • Aashit Shah, M.D., Professor, Virginia Tech Carilion School of Medicine, and Chief of Neurology, Carilion Clinic
  • Michelle Olsen, Ph.D., Associate Professor and Director of Graduate Studies, School of Neuroscience, College of Science, Virginia Tech

Honors

Howard Hughes Medical Institute Medical Research Fellow 2017 – 2018

Presentations

Alcoreza O. Sulfasalazine as a treatment for acquired epilepsy. Poster p0122. Interactive Congress Programme iPlanner. Barcelona, Spain: 32nd International Epilepsy Congress, 2017.

Alcoreza O. Sulfasalazine as a treatment for acquired epilepsy. Program No. 373.08.2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience. Abstract for Poster Presentation.

Publications

Alcoreza O, Tewari BP, Bouslog A, Savoia A, Sontheimer H, Campbell SL. Sulfasalazine decreases mouse cortical hyperexcitability. Epilepsia. 2019;60(7):1365-1377. doi: 10.1111/epi.16073. PMID: 31211419

Alcoreza OB. Science Literacy in the Age of (Dis)Information: A Public Health Concern. Acad Med. 2021 Feb 1;96(2):e12. doi: 10.1097/ACM.0000000000003848. PMID: 33181523.

Alcoreza OB, Patel DC, Tewari BP, Sontheimer H. Dysregulation of Ambient Glutamate and Glutamate Receptors in Epilepsy: An Astrocytic Perspective. Front Neurol. 2021 Mar 22;12:652159. doi: 10.3389/fneur.2021.652159. PMID: 33828523