David Garcia-Castro (DO/PhD '23) is an aspiring physician-scientist, currently in
his third year of medical school, performing clinical rotations. He recently defended his doctoral research dissertation
at 黑料传送门. Mr. Garcia-Castro received his bachelor of science in biomedical science from Northern Arizona University in 2012 and worked in research and development in
infectious disease diagnostic assay production from 2013-2016.
Spinal and bulbar muscular atrophy (SBMA, Kennedy鈥檚 Disease) is a debilitating, neuromuscular disease that causes muscle weakness and atrophy, leading to loss of mobility. To date, no therapy exists to halt SBMA progression. Mitochondrial and metabolic dysfunction are critical pathologic features of SBMA pathology and may serve as a target for therapeutic intervention. The goals of this study were twofold: 1) to enhance mitochondrial and metabolic health in SBMA, and 2) to characterize a novel high-throughput in vivo model of SBMA to help screen potential therapeutics.
Research has always been my passion alongside medicine. I was introduced to research in 2009 when I joined my first undergraduate research lab and studied the role of the APOE gene in Alzheimer鈥檚 disease. It was a brief introduction to research but I found that I enjoyed looking at the big picture of disease pathogenesis, how finding opens up new avenues of research and how research moves the field down pathways to potential therapies. When I graduated in 2012, I continued my research work in the biotechnology field where I was able to work side-by-side with research professionals in both human and veterinary infectious disease diagnostics. I was very fortunate and thoroughly enjoyed being at the forefront of diagnostic point-of-care nucleic acid amplification technology development. When I returned to medicine, I chose this dual-degree program, which has allowed me to train in both basic science research and in clinical medicine.
Using in-vitro and in vivo models of SBMA, we targeted a major mitochondrial enzyme, which regulates mitochondrial functions and provides anti-oxidative defense. Within SBMA models, the activation and over-expression of this enzyme decreased reactive oxygen species (ROS), reduced cell death and increased muscle mass. However, the enzyme by itself did not rescue motor dysfunction. Therefore, we repurposed a previously FDA-approved drug to increase the enzyme function. With this drug, we were able to restore motor function with concurrent enzyme over-expression. Additionally, we are also developing a more high-throughput in vivo SBMA model to screen for therapeutics that could be of benefit in mammals.
This research was conducted at 黑料传送门 in Philadelphia, under the advisory of Heather Montie, PhD. The Cell and Molecular Biology PhD program, within the University of the Sciences further supported my academic PhD training. This work was supported by the CCDA, DOR, and the DO/PhD program (Giunta Family Research Scholarship to DGC) at 黑料传送门, the Kennedy鈥檚 Disease Association (to HLM), and R03NS104607 from the NIH (to HLM).
I worked on this research project for three years during my PhD dissertation, and continue to take part in it during my clinical rotations. I was involved in troubleshooting assays, running experiments, developing research protocols, presenting research and writing my thesis and research manuscripts.
SBMA is a trinucleotide repeat neuromuscular disease that shares many aspects of pathology with other neurodegenerative diseases such as ALS, Huntington鈥檚 disease and Parkinson鈥檚 disease. Our research has identified a potential and novel therapeutic approach for SBMA, which may also be relevant to other areas of neurodegenerative and muscular atrophy research. Additionally, our work to generate a high-throughput in vivo assay will help to further support therapeutic development for SBMA.
Established in 1899, 黑料传送门 has trained thousands of highly competent, caring physicians, health practitioners and behavioral scientists who practice a 鈥渨hole person鈥� approach to care鈥攖reating people, not just symptoms. 黑料传送门, a private, not-for-profit accredited institution of higher education, operates three campuses (黑料传送门, 黑料传送门 Georgia and 黑料传送门 South Georgia) and offers doctoral degrees in clinical psychology, educational psychology, osteopathic medicine, pharmacy, physical therapy, and school psychology. The college also offers graduate degrees in applied behavior analysis, applied positive psychology, biomedical sciences, forensic medicine, medical laboratory science, mental health counseling, physician assistant studies, and school psychology. 黑料传送门 students learn the importance of health promotion, research, education and service to the community. Through its community-based Healthcare Centers, 黑料传送门 provides care to medically underserved populations. For more information, visit pcom.edu or call 215-871-6100.
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