Pagliarini chanced into groundbreaking mitochondrial research

Dave Pagliarini’s research career had a bumpy start. By his third year of graduate school, he had followed his advisers to three labs across the Midwest and West Coast. He finished his Ph.D. in biomolecular sciences at the University of California, San Diego. Pagliarini learned a lot from each adviser, he said, and “those challenges became my accelerators.”

Those accelerators have propelled him through almost a decade of productive mitochondria research, for which Pagliarini will receive the American Society for Biochemistry and Molecular Biology’s 2020/2021 Earl and Thressa Stadtman Young Scholar Award.

Morgridge Institute for Research

Dave Pagliarini

Pagliarini got into mitochondria research by chance when, as a grad student, he identified a new mitochondrial phosphatase that plays a critical role in biosynthesis of the essential cardiolipin required for optimal mitochondrial bioenergetics. This discovery led him to look for other mitochondrial proteins with unknown functions that could play a role in mitochondrial diseases.

Mitochondrial diseases affect one in every 4,000 individuals; uncharacterized mitochondrial proteins contribute to diseases such as mitochondrial encephalomyopathy, a neurodegenerative disorder for which there are no curative treatments.

During his postdoc in Vamsi Mootha’s laboratory at Harvard, Pagliarini established a compendium of more than 1,000 mitochondrial proteins by combining in-depth computational biology and biochemistry. He called it MitoCarta and published his findings in the journal Cell. Although this approach at first provided only a descriptive dataset, what set Pagliarini apart from others in his field was “his ability … to gain understanding of underlying cellular, biochemical, and physiological processes and mechanisms,” Christopher Newgard wrote in a letter supporting the award nomination.

Pagliarini is now the lead investigator and Arthur C. Nielsen chair of metabolism at the Morgridge Institute for Research. His lab works to discover additional orphan mitochondrial proteins and characterize them from molecular to organ level.