Gerald W. Dorn
Medical University of South Carolina, SC·Medicine & Clinical Research
Heart muscle runs on energy made by mitochondria, the cell's power plants, which make up 30–40% of the heart's weight. A healthy adult heart prefers to burn fats, while a fetal heart, and an adult heart with disease, burns mostly sugars.
- Fields
Medicine & Clinical Research
Physiology
Pharmacology
- Topics
mitofusin 2
mitochondria
mitophagy
- Grants
- 1 known grant, through Dec 2030
What they work on
- Determine how PINK1 phosphorylation (the addition of phosphate tags) switches MFN2 between closed and open shapes, exposing or hiding binding sites that decide whether MFN2 drives mitochondrial fusion or mitophagy.
- Test whether human MFN2 mutations harm heart muscle cells mainly by disrupting MFN2–Parkin mitophagy, using MFN2 mutants delivered by adenoviral vectors and knock-in mice.
- Test whether MFN2 mutations harm neurons mainly by impairing MFN2–Miro control of how mitochondria move, explaining why different mutations damage different tissues.
- Evaluate mitofusin-activating small molecules as a preclinical approach to match mitochondrial quality and fuel use to the needs of diseased hearts.
More about the research
This switch in fuel matters because mitochondrial problems contribute to heart enlargement (hypertrophy), heart failure and heart attack. The work asks how the heart changes fuel. Its answer so far is that, much as a gasoline car cannot be reprogrammed into an electric one, the heart must remove its old mitochondria and build new ones suited to the new fuel.
Why it matters
Hypertrophy, heart failure and heart attack all involve mitochondria that are poorly matched to the fuel the heart has available. The project could support a new way to manage heart disease: drugs, such as the lab's mitofusin activators, that tune the quality and number of mitochondria to improve contraction or repair. Rare MFN2-pathway mutations found in patients may also point to a previously unrecognized cause of heart failure.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Peng Yao
University of Rochester, NY·Physiology
Determine how FAM210A regulates mitochondrial calcium balance, testing whether it acts as a regulator of the calcium/proton exchanger LETM1 in cardiomyocytes, in vitro and in vivo.
Faqian Li
University of Texas Health Science Center at San Antonio, TX·Medicine & Clinical Research
Profile heart-specific TCF7L2 isoforms and their target genes in failing human hearts from patients with coronary artery disease and idiopathic dilated cardiomyopathy, to see how they direct β-catenin-driven gene activity.
Phillip Yang
Stanford University, CA·Medicine & Clinical Research
Confirm that a cluster of six proteins enriched in mitochondria-rich extracellular vesicles drives the production of new mitochondria, testing their interaction with PGC-1α, the master regulator of mitochondrial biogenesis that is depleted in failing hearts.
The school
Medical University of South Carolina: 19 labs on PI Pages, $321M a year on research, 271 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.