Michael Kyba, PhD

Dr. Kyba's research laboratory focuses on regulation of tissue-specific stem cells (hematopoietic and skeletal muscle) with a view towards ex-vivo expansion and therapeutic transplantation, as well as the derivation of tissue-specific stem cells from embryonic or iPS cells. He is also developing methods of performing BMT without irradiation or chemical conditioning. He has performed seminal experiments establishing the proof of principle for hematopoietic stem cell repopulation using embryonic stem cells and maintains an active program in the development of gene-targeting / genetic correction / cell therapy models.

Deriving therapeutic hematopoietic stem cells from embryonic stem cells.

ES cells are totipotent and capable of recapitulating all of the developmental events of embryogenesis. They are therefore theoretically the ideal source of cells for regenerative therapies. However, turning theory into practice is not straightforward, and very few successful models of such therapy exist. We have developed one successful model, based on regulated expression of members of the Hox family of transcription factors. Current work is focused on understanding how Hox genes regulate hematopoietic stem cell self-renewal and identifying regulatory circuits under Hox control.

Skeletal muscle stem cells and FSH muscular dystrophy

Certain degenerative diseases may be the result of ineffective self-renewal or differentiation of lineage specific stem cells. We are particularly interested in Fascioscapulohumeral Muscular Dystrophy (FSHD), a dominant dystrophy associated with a contraction of 4q subtelomeric repeats. Although the condition is almost certainly caused by derepression of a gene in the vicinity of 4q, the protein products of candidate genes in this area can not be detected overexpressed in patient muscle samples. Because muscle stem cells (satellite cells) are rare, proteins overexpressed specifically in satellite cells are unlikely to be identified in patient biopsies. We are testing the hypothesis that a Hox gene embedded within the 4q repeats, DUX4, causes FSHD when derepressed in muscle satellite cells.

Stem cell biology

Our long-term goal is to understand the pathways that control self-renewal vs differentiation of stem cells and to use this knowledge to understand degenerative diseases and to design and improve cell therapies. Our work is interdisciplinary, spanning iPS cell-based and animal models involving transplantation and tracking of somatic stem cells, vector development, CRISPR and TALEN-mediated genome editing, and cell-based screening and medicinal chemistry.