Jeanette M. and Joseph S. Silber Professor of Brain Sciences
Professor, Department of Physiology and Biophysics, School of Medicine
Area of Focus: mitochondrial quality control, cellular metabolism, immune responses and the mechanisms underlying neurodegenerative diseases.
Fourteen years ago, Xin Qi joined the Department of Physiology and Biophysics at Case Western Reserve University School of Medicine with a vision to bridge basic mitochondrial research with therapeutic development.
Today, that mission continues to drive her work as she investigates how mitochondrial dysfunction contributes to neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis (ALS). Qi focuses particularly on how mitochondrial protein and genome quality control influence metabolism, immune signaling, and cell survival during disease progression.
“Neurodegenerative diseases affect millions of people worldwide, yet we still lack treatments that can slow or stop disease progression,” Qi said. “Mitochondrial dysfunction is a shared feature across many of these conditions, but it’s an underexplored target for therapy.”
As co-director of the Center for Mitochondrial Research and Therapeutics, Qi collaborates with faculty in the Departments of Neurosciences, Pharmacology, Genetics and Genome Sciences, and Pathology to uncover mitochondrial mechanisms underlying disease. Their goal is to target these pathways and develop therapies with the potential to benefit multiple conditions.
“Ultimately, we aim to help build the foundation for a new class of mitochondrial-based therapies that can make a meaningful impact for patients and families,” she said.
One breakthrough in Qi’s research came with the discovery of how ATAD3A—an understudied mitochondrial protein—can form harmful clumps in brain disease and trigger the body’s immune response, leading to inflammation.
“That insight opened a new line of investigation into how mitochondrial dysfunction drives neuroinflammation,” said Qi, who has since developed cyclic peptides to restore ATAD3A function. “It challenged the view of mitochondria as mere metabolic engines and revealed their active role in immune regulation and inflammation.”
As the team investigated how impaired mitochondrial quality control contributes to disease progression, they identified key pathways disrupted across multiple disorders—particularly those involving mitochondrial genome maintenance, membrane dynamics, and proteostasis, the process by which cells maintain healthy, functioning proteins.
They found that such disruptions can trigger protein aggregation, mitochondrial stress, inflammation, and ultimately neuronal death. In response, Qi and her colleagues developed peptide-based and small-molecule tools to restore these pathways and tested them in patient-derived neurons and diseased animal models.
“We study the biology of mitochondria in depth, but our focus is always on translating that knowledge into meaningful advances for human health,” Qi said. “It’s rewarding to see how advances in mitochondrial biology can lead to new ways of understanding—and potentially treating—complex brain diseases.”