Kyoko Yokomori
University of California-Irvine, CA·Genetics
Facioscapulohumeral dystrophy (FSHD) is one of the most common muscular dystrophies in the United States, and it has no effective treatment. It is also a genetic puzzle.
- Fields
Genetics
Biochemistry
Physiology
- Topics
facioscapulohumeral dystrophy
muscular dystrophy
D4Z4 repeat
- Grants
- 1 known grant, through May 2027
What they work on
- 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.
- Characterize the timing, dynamics, and regulation of DUX4 expression and of its target genes in patient and engineered human muscle cells, including cells with no detectable DUX4.
- Identify modifier genes that dictate FSHD susceptibility and severity, testing whether they explain why some muscles and some patients are far more affected than others.
- Define the epigenetic changes — how DNA is packaged and silenced — caused by D4Z4 contraction versus SMCHD1 loss in an otherwise identical cell background.
More about the research
In more than 95% of cases, patients have lost copies of a repeated stretch of DNA called D4Z4, sitting near the end of chromosome 4; the remaining cases instead carry mutations in SMCHD1, a gene that helps keep DNA packaged in a silenced state. Both routes lead to expression of DUX4, a gene buried inside the D4Z4 repeat whose protein is toxic to muscle cells. But the simple story — DUX4 kills muscle — does not fit the numbers: only about 0.1% of a patient's muscle cells seem to express DUX4, and it occasionally appears in healthy people's muscle too. Because the D4Z4 repeat and several key DUX4 target genes exist only in primates, the disease is also hard to model in mice.
Why it matters
FSHD affects many patients with no treatment available and an unclear mechanism. By modeling each FSHD mutation in human muscle cells and identifying genes that determine which muscles are hit and how hard, the work could point to new therapeutic targets and to markers that help predict disease severity in patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Darko Bosnakovski
University of Minnesota, MN·Genetics
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.
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 California-Irvine: 46 labs on PI Pages, $645M a year on research, 524 research doctorates a year.
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