Deneen M Wellik
University of Wisconsin-Madison, WI·Biology
Our bodies are laid out along a head-to-tail plan, and a family of master control genes called Hox genes helps set that plan, telling cells in each region what to become. Hox genes have long been known to shape the skeleton, yet how they work inside cells remains largely unknown.
- Fields
Biology
Genetics
Physiology
- Topics
Hox genes
Hox11
Hoxa11
- Grants
- 2 known grants, through Feb 2030
What they work on
- 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).
- Test what Hoxa11-lineage cells do for muscle by removing them with Hoxa11-CreERT2-driven cell ablation and by deleting Hox11 function. Use -omic technologies to define functional subsets and cellular mechanisms.
- Compare how Hoxa11-lineage cells behave in culture and after transplantation into tissue outside the body with other muscle-forming cells, such as Pax7-lineage muscle stem cells.
- Map how Hox11-expressing skeletal progenitors develop into cartilage and bone during fracture healing. Use Hoxa11eGFP reporter mice, lineage labeling and single-cell analysis, with and without adult deletion of Hoxd11.
- Compare gene expression in normal and Hox11-mutant skeletal progenitors during timed bone and cartilage differentiation in culture, to find pathways needed to complete differentiation.
- Identify where Hox11 transcription factors bind DNA in skeletal progenitors and early differentiating cells, using newly validated FLAG epitope-tagged Hoxa11 and Hoxd11 alleles.
More about the research
This research follows Hox11 genes, which are active in the forearm and lower leg, in two kinds of support cells. One kind is the stem and progenitor cells that build bone and cartilage. The other is the stromal cells, a type of connective-tissue cell found between muscle fibers. Both projects rely on genetic tools that the team built in mice to see, trace, delete or tag Hox-expressing cells.
Why it matters
Understanding a newly recognized pool of Hox-expressing muscle progenitor cells could open new ways to reduce muscle loss in muscle diseases such as the dystrophinopathies and in aging. Identifying the genes that Hox factors control in skeletal stem cells could improve knowledge of human skeletal growth and of how fractures heal. Hox genes are expressed in a similar, region-specific way in skeletal progenitors across vertebrates, including humans.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Archana Sanjay
University of Connecticut, CT·Biology
Test whether Rspo2 and Rspo3 are needed in mesenchymal progenitors for fracture healing, by deleting these genes at the time of fracture in mice and assessing repair with microCT, histology and mechanical testing.
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.
Rita Perlingeiro
University of Minnesota, MN·Biomedical Engineering
Determine how the host muscle environment affects engraftment of PSC-derived myogenic progenitors in an immune-deficient FKRP mutant mouse model of dystroglycanopathy.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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