Rita Perlingeiro
University of Minnesota, MN·Biomedical Engineering
Muscular dystrophies are inherited diseases in which skeletal muscle steadily weakens and breaks down, and most have no effective treatment. One hope is to replace damaged muscle with healthy cells grown from pluripotent stem cells (PSCs).
- Fields
Biomedical Engineering
Biology
Genetics
- Topics
muscular dystrophy
dystroglycanopathy
Walker-Warburg syndrome
- Grants
- 3 known grants, through Nov 2027
What they work on
- Determine how the host muscle environment affects engraftment of PSC-derived myogenic progenitors in an immune-deficient FKRP mutant mouse model of dystroglycanopathy.
- Assess the long-term regenerative function and molecular profile of gene-corrected Walker-Warburg syndrome iPS cell-derived and unaffected iPS cell-derived muscle progenitors after transplantation.
- Test scalability, delivery, body distribution, safety and engraftment of cGMP-compatible iPS cell-derived muscle progenitors in non-human primates as a preclinical step toward therapy for muscular dystrophy.
- Compare transplants of matched (autologous) and unmatched (allogeneic) monkey iPS-derived progenitors to learn how HLA mismatch affects muscle engraftment and immune tolerance.
- Identify cues from the adult muscle niche, and the role of post-transcriptional regulation, that shift transplanted PSC-derived progenitors from a fetal-like to an adult-like state.
- Track the clonal dynamics of engraftment and the quiescent (resting) state of donor-derived subgroups of transplanted muscle progenitor cells.
More about the research
These are cells that can multiply almost without limit and turn into any cell type, and they include induced pluripotent stem (iPS) cells reprogrammed from adult cells. The lab has developed a method to turn PSCs into muscle progenitors by switching on Pax3 or Pax7, master genes that start the muscle program. When transplanted into dystrophic mice, these cells form working muscle fibers. Some also become satellite cells, the muscle's own stem cells, which can repair muscle after later injuries. The three projects ask why these cells work, how to apply them to specific diseases, and whether they are safe and effective in larger animals.
Why it matters
No approved therapy exists for FKRP-related dystroglycanopathies, and Duchenne and other muscular dystrophies lack effective treatment. A transplant of stem cell-derived muscle progenitors could rebuild working muscle and supply lasting muscle stem cells, including in the diaphragm, where weakness threatens breathing. The primate studies address safety, scale-up and immune matching, which are needed before testing in patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Targeting Dystroglycanopathies using Pluripotent-derived Myogenic Progenitors
NIH · Feb 2023 – Nov 2027
Skeletal Muscle Regeneration from Pluripotent Stem Cells
NIH · Jun 2021 – May 2027
Preclinical studies of pluripotent stem cell-derived myogenic progenitors in non-human primates
NIH · Aug 2021 – Dec 2026
Closest labs
Wanling Xuan
University of South Florida, FL·Physiology
Test whether muscle progenitor cells made from human iPSCs with givinostat, a histone deacetylase–blocking drug, are effective and safe for regenerating aged muscle in an animal model of sarcopenia.
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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