Darko Bosnakovski
University of Minnesota, MN·Genetics
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited muscle diseases. It often worsens in episodes rather than steadily.
- Fields
Genetics
Physiology
Medicine & Clinical Research
- Topics
facioscapulohumeral muscular dystrophy
D4Z4 repeats
epigenetics
- Grants
- 1 known grant, through Jun 2027
What they work on
- Test whether transient DUX4 expression in the inducible iDUX4pA;HSA mouse model causes lasting changes in muscle physiology and histology (tissue structure) after the gene is switched off.
- Characterize long-term cellular changes after a DUX4 pulse, including increased fibro-adipogenic progenitors (scar-promoting support cells) and excess fibrotic extracellular matrix in mouse muscle.
- Determine whether muscle primed by brief DUX4 expression fails to fully recover after injury, testing whether a pro-degenerative state plus injury produces FSHD-like dystrophy.
- Examine how transient DUX4 alters the epigenetic state of the muscle genome, the chemical marks controlling gene activity, to find a lasting 'echo' independent of DUX4 itself.
More about the research
It is caused when a stretch of chromosome 4 called the D4Z4 repeats loses its normal chemical silencing. This allows a gene called DUX4 to turn on in muscle. Oddly, DUX4 protein has never been directly detected in patient muscle. Its activity is inferred only from raised levels of the genes it controls in patient biopsies. This suggests DUX4 may appear only at very low levels or in brief bursts. The project asks whether such a brief burst is enough to set muscle on a path toward disease.
Why it matters
People with FSHD have no clear explanation for why their muscle weakness progresses in stages. By testing whether brief bursts of DUX4 leave muscle primed to degenerate, this work could clarify disease mechanisms. It could also identify external factors such as injury that worsen FSHD. This may inform when and how future therapies should act.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kyoko Yokomori
University of California-Irvine, CA·Genetics
Generate additional engineered myoblast clones carrying D4Z4 repeat deletion, SMCHD1 mutation, or both, to compare how FSHD mutations behave in muscles with different disease susceptibility and during early muscle differentiation.
Michael Lopez
University of Alabama at Birmingham, AL·Genetics·Early-career
Test how over-expressing or knocking down Smad8, a TGF-beta–linked transcription factor elevated in Duchenne muscle, changes muscle cell growth, maturation and regeneration in cell culture and Duchenne mouse models.
Deneen M Wellik
University of Wisconsin-Madison, WI·Biology
Trace what Hoxa11-expressing muscle interstitial cells become in living mice, using Hoxa11-CreERT2 lineage labeling (a genetic switch that permanently marks these cells) after muscle injury and during induced muscle hypertrophy (growth).
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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