Kyba Lab/Experimental Tissue Regeneration Lab

Laboratory Focus:

Our work focuses on factors regulating tissue degeneration and regeneration, with a view towards using cell therapy for regenerative medicine. The work spans two organ systems: the hematopoietic and the skeletal muscle systems and focuses on the role of transcription factors that regulate the regenerative response, or lead to degeneration when they go awry.

Training & Fellowship

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 [email protected] if you are interested in joining the group.

Lab Members

Related Publications

Krauss RS, Kyba M. (2025) “When everything is a master regulator, nothing is” Mol Biol Cell. 2025;36:pe3. doi:10.1091/mbc.E24-11-0494

Wei E, Mitanoska A, O'Brien Q, Porter K, Molina M, Ahsan H, Jung U, Mills L, Kyba M, Bosnakovski D. (2024). “Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma” Molecular cancer, 23:222. https://doi.org/10.1186/s12943-024-02115-7

Pereira IT, Gomes-Júnior R, Hansel-Frose A, França RSV, Liu M, Soliman HAN, Chan SSK, Dudley SC, Kyba M, Dallagiovanna B (2024). “Cardiac Development Long Non-Coding RNA (CARDEL) Is Activated during Human Heart Development and Contributes to Cardiac Specification and Homeostasis” Cells, 13:1050. https://doi.org/10.3390/cells13121050

Vega-Sendino M, Lüttmann FF, Olbrich T, Chen Y, Kuenne C, Stein P, Tillo D, Carey GI, Zhong J, Savy V, Radonova L, Lu T, Saykali B, Kim KP, Domingo CN, Schüler L, Günther S, Bentsen M, Bosnakovski D, Schöler H, Kyba M, Maity TK, Jenkins LM, Looso M, Williams CJ, Kim J, Ruiz S. (2024). “The homeobox transcription factor DUXBL controls exit from totipotency” Nature genetics, 56:697–709. https://doi.org/10.1038/s41588-024-01692-z

Sullivan BP, Larson AA, Shams AS, McMillin SL, Ebeling MC, Peng S, Kyba M, Lowe DA. (2024) “Estradiol deficiency as a consequence of aging contributes to the depletion of the satellite cell pool in female mice” Aging cell. 2024:e14441.

Bedada FB, Thompson BR, Mikkila JL, Chan SS, Choi SH, Toso EA, Kyba M, Metzger JM. (2024) “Inducing positive inotropy in human iPSC-derived cardiac muscle by gene editing-based activation of the cardiac α-myosin heavy chain” Sci Rep. 14:3915

Schneider CA, Leung JM, Valenzuela-Leon PC, Golviznina NA, Toso EA, Bosnakovski D, Kyba M, Calvo E, Peterson KE. (2024) “Skin muscle is the initial site of viral replication for arboviral bunyavirus infection” Nat Commun. 15:1121

Bosnakovski D, Toso EA, Ener ET, Gearhart MD, Yin L, Lüttmann FF, Magli A, Shi K, Kim J, Aihara H, Kyba M. (2023) “Antagonism among DUX family members evolved from an ancestral toxic single homeodomain protein” iScience 26:107823

Ramabadran R, Wang JH, Reyes JM, Guzman AG, Gupta S, Rosas C, Brunetti L, Gundry MC, Tovy A, Long H, Gu T, Cullen SM, Tyagi S, Rux D, Kim JJ, Kornblau SM, Kyba M, Stossi F, Rau RE, Takahashi K, Westbrook TF, Goodell MA. (2023) “DNMT3A-coordinated splicing governs the stem state switch towards differentiation in embryonic and haematopoietic stem cells” Nat. Cell Biol. 25:528-539

Wu R, Park J, Qian Y, Shi Z, Hu R, Yuan Y, Xiong S, Wang Z, Yan G, Ong SG, Song Q, Song Z, Mahmoud AM, Xu P, He C, Arpke RW, Kyba M, Shu G, Jiang Q, Jiang Y. (2023) “Genetically prolonged beige fat in male mice confers long-lasting metabolic health” Nat. Commun. 14:2731

Singh BN, Yucel D, Garay BI, Tolkacheva EG, Kyba M, Perlingeiro RCR, van Berlo JH, Ogle BM. (2023) “Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering” Circ. Res. 132:519-540

Bosnakovski D, Oyler D, Mitanoska A, Douglas M, Ener ET, Shams AS and Kyba M. (2022) “Persistent Fibroadipogenic Progenitor Expansion Following Transient DUX4 Expression Provokes a Profibrotic State in a Mouse Model for FSHD” Int. J. Molecular Sci. 23:1983

Bosnakovski D, Ener ET, Cooper MS, Gearhart MD, Knights KA, Xu NC, Palumbo CA, Toso EA, Marsh GP, Maple HJ, Kyba M. (2021) “Inactivation of the CIC-DUX4 oncogene through P300/CBP inhibition, a therapeutic approach for CIC-DUX4 sarcoma” Oncogenesis 10:1-11

Arpke RW, Shams AS, Collins BC, Larson AA, Lu N, Lowe DA, Kyba M. (2021) “Preservation of satellite number and regenerative potential with age reveals locomotory muscle bias” Skeletal muscle 11:1-12

Bosnakovski D, Shams AS, Yuan C, da Silva MT, Ener ET, Baumann CW, Kyba M. (2020). "Transcriptional and cytopathological hallmarks of FSHD in chronic DUX4-expressing mice" J Clin Invest 103:2465-2477.

Kyba, M. (2020). "Replication of bone-marrow pathophysiology" Nat Biomed Eng 4:364-365.

Larson AA, Baumann CW, Kyba M, Lowe DA. (2020). "Oestradiol affects skeletal muscle mass, strength and satellite cells following repeated injuries" Exp Physiol 10: 1700-1707.

Bosnakovski D, da Silva MT, Sunny ST, Ener ET, Toso EA, Yuan C, Cui Z, Walters MA, Jadhav A, Kyba M, (2019) "A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death" Science Advances 5: eaaw7781.

Collins BC, Arpke RW, Larson AA, Baumann CW, Xie N, Cabelka CA, Nash NL, Hanna-Kaarina J, Laakkonen EK, Sipilä S, Kovanen V, Spangenburg EE, Kyba M, Lowe DA. (2019) "Estrogen Regulates the Satellite Cell Compartment in Females" Cell Reports 28: 368-381

Chan SSK, Arpke RW, Filareto A, Xie N, Pappas MP, Penaloza JS, Perlingeiro RCR, Kyba M. (2018) "Skeletal muscle stem cells from PSC-derived teratomas have functional regenerative capacity" Cell Stem Cell 23:74-85

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