Welcome to the Kyba Lab

Lineage-specific stem cells from ES/iPS cells.
The ability to reprogram somatic cells to the pluripotent state has opened up new possibilities for cell therapy. We are studying the regulatory pathways that give rise to three specific lineages within mesoderm: blood, cardiac, and skeletal muscle, with the goal of applying this knowledge to the generation of therapeutic lineage-restricted stem cells suitable for regenerative medicine. 

The Hox code for hematopoietic stem cell self-renewal.

Gain of function studies with HoxB4 have shown that this Hox family member is involved in the regulation of self-renewal. Unfortunately, because other Hox genes cause leukemia when constitutively expressed, they have largely been ignored. By using conditional gene expression, we have shown that HoxB4 is neither unique in promoting hematopoietic stem cell self-renewal, nor most potent. We wish to understand how Hox genes control stem cell self-renewal, and are identifying regulatory circuits under Hox control. 

Lineage-specific reprogramming of somatic cells.
The use of 4 transcription factors to convert somatic cells into pluripotent cells, together with earlier studies on MyoD-mediated reprogramming of cell fate show that radical intervention in the system for specifying and maintaining cell fate is possible simply by expressing key transcription factors. We have found a transcription factor cocktail that drives blood development at high efficieny, and are applying this approach towards the goal of generating hematopoietic stem cells directly from somatic cells, bypassing the pluripotent state.

Skeletal muscle stem cells and iPS cells from FSH muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD), the third most common muscular dystrophy with a prevalance approaching that Duchenne's, is caused by chromatin changes associated with a contraction of macrosatellite repeats at 4qter. How these chromatin changes cause disease is not understood. The macrosatellite repeat encodes a Hox gene named DUX4, with homeodomains similar to those of Pax7. We have shown that DUX4 and Pax7 can compete for control of expression of myogenic regulators such as MyoD, and are testing the hypothesis that DUX4, expressed in satellite cells, interferes with myogenesis in FSHD-affected muscle. Because satellite cells are rare and difficult to access, we have generated iPS cells from FSHD patients, and are studying chromatin changes and gene expression at 4qter that occur with the development of the muscle lineage and skeletal muscle stem cells in vitro.

A rotation position is currently open. Students enrolled in a UMN graduate program and interested in pursuing studies on the regulation of blood or muscle stem cells or muscular dystrophy should contact Dr. Kyba by email.

Postdoctoral positions are available. Candidates with an interest in molecular regulation of blood, cardiac or skeletal muscle stem cells or the misregulation of muscle stem cells in muscular dystrophy should send a C.V. and contact information for three references to Dr. Kyba by email.