Primary Mitochondrial Disease Patient Treatment and Characterization
Tuesday, May 26, 2026
12:00 PM-2:00 PM
BIOMED PhD Research Proposal
Title:
Primary Mitochondrial Disease Patient Treatment and Characterization
Speaker:
Kelsey Keith, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
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Advisors:
Marni J. Falk, MD
Executive Director
Mitochondrial Medicine Frontier Program
Distinguished Endowed Chair
Department of Pediatrics
Children's Hospital of Philadelphia (CHOP)
Professor, Division of Human Genetics
Department of Pediatrics
University of Pennsylvania Perelman School of Medicine
Ahmet Sacan, PhD
Teaching Professor
School of Biomedical Engineering, Science and Health Systems
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Details:
Primary mitochondrial diseases (PMD) are a heterogeneous group of rare, inherited disorders caused by mutations in mitochondrial or nuclear DNA that disrupt mitochondrial function. Although two therapies received FDA approval in 2025, treatment options for most patients remain limited, and the mechanisms underlying the marked genotype–phenotype variability in PMD are poorly understood. This proposal seeks to improve understanding of PMD pathophysiology and therapeutic strategies by integrating unbiased multiomics profiling, high-throughput drug screening, and mechanistic studies to identify novel disease pathways, therapeutic targets, and candidate treatments. We hypothesize that comprehensive molecular characterization combined with whole-organism screening approaches will uncover conserved and mutation-specific mechanisms that drive PMD and reveal actionable therapeutic opportunities.
To address this hypothesis, we will perform transcriptomic and metabolomic profiling across multiple zebrafish models of PMD to characterize disease heterogeneity and identify dysregulated metabolic pathways and druggable targets. In parallel, we will leverage high-throughput screening of 2,560 FDA-approved compounds in C. elegans PMD models using fluorescent reporters of mitochondrial stress and function to identify candidate therapeutics and uncover previously unrecognized treatment targets. Finally, we will investigate the mechanism of action of cycloheximide, a compound found to improve mitochondrial disease phenotypes despite concerns regarding toxicity, through aptamer-based proteomics to define the specific pathways responsible for its therapeutic effects and guide development of safer targeted alternatives.
The expected outcomes of this work include the identification of reproducible therapeutic candidates suitable for preclinical development or clinical translation, particularly among already FDA-approved compounds, as well as the discovery of novel molecular targets and mechanistic insights into PMD biology. Collectively, this research will advance both the fundamental understanding of mitochondrial disease and the development of effective targeted therapies for patients with PMD.
Contact Information
Natalia Broz
njb33@drexel.edu