Michael Kyba, PhD
Professor and Lillehei Endowed Scholar
Carrie Ramey / CCRF Endowed Professor in Pediatric Cancer Research,
Department of Pediatrics
Professor and Lillehei Endowed Scholar
Carrie Ramey / CCRF Endowed Professor in Pediatric Cancer Research, Department of Pediatrics
Postdoctoral Fellowship, Massachusetts Institute of Technology - Whitehead Institute (Stem Cell Biology), 2003
PhD, University of British Columbia (Zoology), 1998
Dr. Kyba is a Professor of Pediatrics and Carrie Ramey / CCRF Endowed Professor in Pediatric Cancer Research in the Department of Pediatrics' Division of Blood and Marrow Transplantation. He is also an Endowed Scholar of the Lillehei Heart Institute, and an affiliate member of the Stem Cell Institute. Dr. Kyba received his PhD degree from the University of British Columbia in 1998, and completed a postdoctoral fellowship in stem cell biology at the Whitehead Institute at MIT, Cambridge, MA in 2003. From 2003-2008, he was Assistant Professor of Developmental Biology at the University of Texas Southwestern Medical Center at Dallas, TX. He joined the faculty at the University of Minnesota in July 2008. Dr. Kyba has published over 100 research manuscripts in scientific journals, including: Cell, Science, and Nature Medicine.
Dr. Kyba is a Professor of Pediatrics and Carrie Ramey / CCRF Endowed Professor in Pediatric Cancer Research in the Department of Pediatrics' Division of Blood and Marrow Transplantation. He is also an Endowed Scholar of the Lillehei Heart Institute, and an affiliate member of the Stem Cell Institute.
Dr. Kyba received his PhD degree from the University of British Columbia in 1998, and completed a postdoctoral fellowship in stem cell biology at the Whitehead Institute at MIT, Cambridge, MA in 2003. From 2003-2008, he was Assistant Professor of Developmental Biology at the University of Texas Southwestern Medical Center at Dallas, TX. He joined the faculty at the University of Minnesota in July 2008.
Dr. Kyba has published over 100 research manuscripts in scientific journals, including: Cell, Science, and Nature Medicine.
Awards & Recognition
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.
A selection of Dr. Kyba’s Recent Publications
- HoxA3 is an apical regulator of haemogenic endothelium. Iacovino M, Chong D, Szatmari I, Hartweck L, Rux D, Caprioli A, Cleaver O, Kyba M. Nat Cell Biol. 2011 Jan;13(1):72-8. doi: 10.1038/ncb2137. Epub 2010 Dec 19.
- A new immuno- dystrophin-deficient model, the NSG-mdx4Cv mouse, provides evidence for functional improvement following allogeneic satellite cell transplantation. Arpke RW, Darabi R, Mader TL, Zhang Y, Toyama A, Lonetree C, Nash N, Lowe DA, Rita C.R. Perlingeiro, Kyba M. Stem Cells. 2013 31:1611-1620. doi: 10.1002/stem.1402.
- A focal domain of extreme demethylation within D4Z4 in FSHD2. Hartweck LM, Anderson LJ, Lemmers RJ, Dandapat A, Toso EA, Dalton JC, Tawil R, Day JW, van der Maarel SM, Kyba M. Neurology. 2013 80:392-299. doi: 10.1212/WNL.0b013e31827f075c. Epub 2013 Jan 2.
- Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner. Chan SS, Shi X, Toyama A, Arpke RW, Dandapat A, Iacovino M, Kang JJ, Le G, Hagen HR, Garry DJ, Kyba M. Cell Stem Cell. 2013 12:587-601. doi: 10.1016/j.stem.2013.03.004.
- High-throughput screening identifies inhibitors of DUX4-induced myoblast toxicity. Bosnakovski D, Choi SH, Strasser JM, Toso EA, Walters MA, Kyba M. Skeletal Muscle. 2014 (1):4. doi: 10.1186/2044-5040-4-4.
- Expression of the human FSHD-linked DUX4 gene induces neurogenesis in pluripotent cells. Dandapat A, Hartweck L, Kyba M. Stem Cells and Development 22:2440-2448. 2013.
- Generation of functional thyroid from embryonic stem cells. Antonica F, DF Kasprzyk, R Opitz, Iacovino M, Liao XH, Dumitrescu AM, Refetoff S, Peremans K, Manto M, Kyba M, Costagliola S. Nature 491:66-71. 2012
- Human ES- and iPS-Derived Myogenic Progenitors Restore DYSTROPHIN and Improve Contractility upon Transplantation in Dystrophic Mice. Darabi R, Arpke RW, Irion S, Dimos JT, Grskovic M, Kyba M, Perlingeiro RC. Cell Stem Cell 10:610-619. 2012.
- Inducible cassette exchange: a rapid and efficient system enabling conditional gene expression in embryonic stem and primary cells. Iacovino M, Bosnakovski D, Fey H, Rux D, Bajwa G, Mahen E, Mitanoska EA, Zu Z, Kyba M. Stem Cells 29:1580-1588. 2011.
- An isogenetic myoblast screen identifies DUX4-mediated FSHD-associated molecular pathologies. Bosnakovski D, Xu Z, Gang EJ, Galindo CL, Liu M, Simsek T, Garner HR, Agha-Mohammadi S, Tassin A, Frédérique Coppée, Belayew A, Perlingeiro RCR, Kyba M. EMBO J. 27:2766-2779. 2008.
- White fat progenitor cells reside in the Adipose Vasculature. Tang W, Zeve D, Suh J, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM. Science 322:583-536. 2008.
- Functional skeletal muscle regeneration from differentiating embryonic stem cells. Darabi R, Gelbach K, Bachoo RM, Kamath S, Osawa M, Kamm KE, Kyba M, Perlingeiro RCR. Nature Medicine 14:134-143. 2008.
- Prospective isolation of skeletal muscle stem cells with a Pax7 reporter. Bosnakovski D, Xu Z, Li W, Thet S, Cleaver O, Perlingeiro RCR, Kyba M. Stem Cells 26:3194-3204. 2008.
Click here to see a complete list of Dr. Kyba’s studies which have been published by academic and research journals.