Laboratory of Experimental Tissue Regeneration

Specific projects:

Regulation of satellite cell quiescence and self-renewal: Skeletal muscle has tremendous capacity for regeneration after injury, but does not normally experience significant turnover. Satellite cells, the stem cells for skeletal muscle, are therefore quiescent. We are investigating mechanisms of regulation that govern quiescence and self-renewal of satellite cells, with a long-term goal of applying these to cell therapies for muscle diseases.

DUX4 and FSHD: The genetic disease facioscapulohumeral muscular dystrophy is caused by mutations leading to inappropriate expression of the double homeodomain transcription factor, DUX4. We are investigating the molecular mechanisms by which DUX4 recognizes DNA, alters chromatin and activates transcription, and are actively engaged in a program to discover and develop small molecule inhibitors of DUX4 for the treatment of FSHD. We have also developed an animal model for FSHD based on regulated, titratable expression of DUX4 in skeletal muscle.

DUX4 and cancer: Translocations that insert DUX4 into the IgH locus cause childhood and adolescent B cell leukemia. We are investigating the molecular mechanism underlying the oncogenic activity of DUX4-IGH fusion proteins. In addition, CIC-DUX4 fusions lead to an aggressive pediatric sarcoma named CDS. We are investigating new approaches for treating CDS based on inhibition of DUX4 and its cofactors, p300 and CBP.

Repopulating hematopoietic stem cells from pluripotent stem cells: We established the first efficient system for doing this in the mouse model, but the field still has not been able to generate repopulating HSCs from human iPS cells in an efficient manner. We are investigating novel approaches to differentiation of pluripotent stem cells in an effort to enable bone marrow transplantation from iPS cells.

Postdoc, graduate and undergraduate student positions are available. Please contact Dr. Michael Kyba at kyba@umn.edu if you are interested in joining the group.