Dr. Radbod Darabi, M.D, Ph.D.

Dr. Radbod Darabi, M.D, Ph.D.

Associate Professor, Center for Stem Cell & Regenerative Medicine; Jerold B. Katz Distinguished Professorship in Stem Cell Research

Email Address: Radbod.Darabi@uth.tmc.edu
Phone Number: 713-500-3411
Room Number: SRB 630C

Narrative

“Human Induced Pluripotent Stem Cells (hiPSCs) for Skeletal Muscle Disease Modeling and Repair”

The overall focus of our lab is to use human pluripotent stem cells (hiPSCs) for skeletal muscle regeneration. During last several years, we have developed efficient methods for directed differentiation of hiPSCs toward skeletal muscle lineage. By using CRISPR/Cas9 gene editing technology and incorporation of site-specific reporters, we have developed several reporter hPSC lines for major myogenic transcription factors (PAX7, MYF5). This strategy allows for pathway and chemical screen to identify major myogenic inducers, surface marker screen and eventually development of the efficient myogenic induction in hiPSCs and their purification. In addition, we are interested in generation of new iPSCs from patients suffering from different types of muscular dystrophies, to model the disease in vitro and design gene correction strategies. Another focus of the lab is on the therapeutic application of hiPSCs for volumetric muscle loss injuries (VML), which are very common during accidents, after reconstruction surgeries and in combat injuries. By using human pluripotent stem cells along with appropriate bioscaffold, we aim to evaluate the engraftment and functional recovery potential of this approach in animal models of VML.

Our lab is currently funded by two NIH (R01) grants to support these projects.

Ongoing Research Projects

    1. Directed differentiation of human pluripotent stem cells toward myogenic progenitors using knock-in reporters for PAX7 and MYF5
    2. hiPSC disease modeling and CRISPR/Cas9 mediated gene correction for new types of LGMDs
    3. Evaluation of the role of POGLUT1 (RUMI) in skeletal muscle maintenance and repair
    4. Therapeutic application of hiPSCs for volumetric muscle loss injury (VML) repair
    5. In vivo and in situ muscle function analysis to determine the effect of stem cell therapy in muscle function restoration

      Selected Publications

        1. Wu J, Mathias N, Bhalla S, Darabi R, Evaluation of the Therapeutic Potential of Human iPSCs in a Murine Model of VML. Molecular Therapy. 2020 Sep 6:S1525-0016(20)30469-X.
        2. Wu J, Matthias N, Lo J, Ortiz-Vitali JL, Shieh AW, Wang SH, Darabi R. A Myogenic Double-Reporter Human Pluripotent Stem Cell Line Allows Prospective Isolation of Skeletal Muscle Progenitors. Cell Reports. 2018 Nov. 25/7:1966-1981. PMCID: PMC6287935
        3. Matthias N, Hunt SD, Wu J, Lo J, Smith Callahan LA, Li Y, Huard J, Darabi R. Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with muscle-derived stem cells (MDSCs). Stem Cell Research. 2018 Mar; 27:65-73.  PMCID: PMC5851454
        4. Wu J, Hunt SD, Matthias N, Servián-Morilla E, Lo J, Jafar-Nejad H, Paradas C, Darabi R. Generation of an induced pluripotent stem cell line (CSCRMi001-A) from a patient with a new type of limb-girdle muscular dystrophy (LGMD) due to a missense mutation in POGLUT1 (Rumi). Stem Cell Research. 2017 Oct; 24:102-105.  PMCID: PMC5679726
        5. Wu J, Hunt SD, Xue H, Liu Y, Darabi R. Generation and Validation of PAX7 Reporter Lines from Human iPS Cells Using CRISPR/Cas9 Technology. Stem Cell Research. 2016 Jan 13; 16(2):220-228.
        6. Wu J, Hunt SD, Xue H, Liu Y, Darabi R. Generation and Characterization of a MYF5 Reporter Human iPS Cell Line Using CRISPR/Cas9 Mediated Homologous Recombination. Scientific Reports. 2016 Jan 5;6:18759.
        7. Matthias N, Hunt SD, Wu J, Darabi R. Skeletal muscle perfusion and stem cell delivery in muscle disorders using intra-femoral artery canulation in mice. Experimental Cell Research. 2015 Nov 15;339(1):103-11.
        8. Darabi R, Arpke RW, Irion S, Dimos JT, Grskovic M, Kyba M, Perlingeiro RC. Human ES and iPS-Derived Myogenic Progenitors Restore Dystrophin and Improve Contractility upon Transplantation in Dystrophic Mice. Cell Stem Cell. 2012 May; 10 (5), 610-619.  PMCID: PMC3348507
        9. Darabi R, Santos FN, Filareto A, Pan W, Koene R, Rudnicki MA, Kyba M, Perlingeiro RC. Assessment of the myogenic stem cell compartment following transplantation of pax3/pax7-induced embryonic stem cell-derived progenitors. Stem Cells. 2011 May; 29(5):777-90.  PMCID: PMC3325545
        10. Darabi R, Gehlbach K, Bachoo MR, Kamath S, Osawa M, Kam KE, Kyba M, Perlingeiro RC. Functional skeletal muscle regeneration from differentiating embryonic stem cells. Nature Medicine. 2008; 14 (2): 134-143.

        Complete List of Publications:

        https://www.ncbi.nlm.nih.gov/myncbi/radbod.darabi.1/bibliography/public/


        DARABIfigure1photo2020final

        Directed Differentiation of hiPSCs toward Skeletal Myogenic Progenitors

        (A) Differentiation time course and expression profile of the reporters

        (B) In vitro differentiation of the sorted cells and formation of myotubes

        (C) In vivo engraftment of the hiPSCs into dystrophic muscle of a mouse model for DMD

        DARABIfigure2photo2020final

        hiPSCs for Volumetric Muscle Loss (VML) Injury Repair

        (A) VML model and its repair using hiPSC-derived myogenic cells and a hydrogel

        (B) VML repair and formation of hiPSC-derived myofibers

        (C) Formation of muscle stem cells (satellite cells) from hiPSCs after VML repair