Research Interests

Stem cells exist in most organs in the body and are responsible for tissue homeostasis and repair. These rare cells hold the promise of novel therapeutics for degenerative diseases for which there are currently no cures or even effective treatments. Many questions remain unanswered about how stem cell functions are regulated and how they are impacted by changes in the local and systemic environment during aging or in disease conditions. Using skeletal muscle and the resident muscle stem cells as a model system, our laboratory seeks to understand how stem cells function, how stem cells change with age, and how to restore youthful function to aged stem cells. We take a multi-omics approach to identify critical factors and pathways that regulate fundamental features and processes of muscle stem cells, including the maintenance of quiescence and self-renewal. We use gene editing approaches (CRISPR) both for screening and for specific genetic modifications to study stem cell function, and we develop genetically engineered mice for the purposes of cell labeling, lineage tracing, cell depletion, and bio-orthogonal chemistry. In addition to basic stem cell research, we have pre-clinical translational projects exploring mechanisms of disease progression and experimental therapeutics for muscular dystrophies, and tissue engineering approaches for functional restoration following muscle trauma.

Selected Publications

Colville A, Liu J-Y, Rodriguez-Mateo C, Thomas S, Ishak HD, Zhou R, Klein JDD, Morgens DW, Goshayeshi A, Salvi JS, Yao D, Spees K, Dixon SJ, Rhee JW, Lai C, Wu JC, Bassik MC, Rando TA (2023) Death-seq identifies regulators of cell death and senolytic therapies. Cell Metabol, 35: 1814-1829.

Liu L, Kim S, Buckley MT, Reyes JM, Kang J, Tian L, Wang M, Lieu A, Mao M, Mateo-Rodriguez C, Ishak HD, Jeong M, Wu JC, Goodell MA, Brunet A, Rando TA (2023) Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging. Cell Stem Cell, 30: 689-705.

de Morrée A, Rando TA (2023) Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity. Nature Rev Mol Cell Biol, 24: 334-354.

Benjamin DI, Brett JO, Both P, Benjamin JS, Ishak HL, Kang J, Kim S, de Morree A, Arjona M, Nutter CW, Tan JH, Dulay H, Louie SM, Nomura DK, Rando TA (2023) Multiomics reveals glutathione metabolism as a driver of bimodality during stem cell aging. Cell Metabol, 35: 472-486.

Brunet A, Goodell MA, Rando TA (2023) Ageing and rejuvenation of tissue stem cells and their niches. Nature Rev Mol Cell Biol, 24: 45-62.

Eugenis I, Wu D, Hu C, Chiang G, Huang NF, Rando TA (2022) Scalable macroporous hydrogels enhance stem cell treatment of volumetric muscle loss. Biomaterials, 290: 121818.

Benjamin DI, Both PA, Benjamin JS, Nutter CW, Tan JH, Kang J, Machado LA, Klein JDD, de Morree A, Kim S, Liu L, Dulay H, Feraboli L, Louie SM, Nomura DK, Rando TA (2022) Fasting induces a highly resilient deep quiescent state in muscle stem cells via ketone body signaling. Cell Metabol, 34: 902-918.

De Miguel Z, Betley MJ, Khoury N, Lehallier B, Willoughby D, Olsson N, Bonanno L, Yang A, Vest R, Yerra L, Lee D, Zhang H, Saw NL, Fairchild KJ, Contrepois K, Elias JE, Rando TA, Wyss-Coray T (2021) Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature, 600: 494-499.

Wosczyna MN, Perez Carbajal EE, Wagner MW, Paredes S, Konishi CT, Liu L, Wang TT, Walsh RA, Gan Q, Morrissey CS, Rando TA (2021) Targeting microRNA-mediated gene repression limits the adipogenic conversion of skeletal muscle mesenchymal stromal cells. Cell Stem Cell, 28, 1323-1334.

Tabula Muris Consortium (2020) A single cell transcriptomic atlas characterizes aeging tissues in the mouse. Nature, 583: 590-595.

Brett JO, Arjona M, Ikeda M, Quarta M, de Morrée A, Egner IM, Perandini LA, Ishak HD, Goshayeshi A, Benjamin DI, Both P, Rodriguez-Mateo C, Betley MJ, Wyss-Coray T, Rando TA (2020) Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1. Nature Metabol, 2: 307-317.

de Morree A, Klein JDD, Gan Q, Farup J, Urtasun A, Kanugovi A, Bilen B, van Velthoven CTJ, Quarta M, Rando TA (2019) Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function. Science, 366: 734-738.

Tabula Muris Consortium (2018) Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature, 562: 367-372.

Liu L, Charville GW, Cheung TH, Yoo B, Santos PJ, Schroeder M, Rando TA (2018) Impaired Notch signaling leads to a decrease in p53 activity and mitotic catastrophe in aged muscle stem cells. Cell Stem Cell, 23: 544–556.

Rando TA, Ambrosio F (2018) Regenerative rehabilitation: Applied biophysics meets stem cell therapeutics. Cell Stem Cell, 22: 306-309.

van Velthoven CTJ, de Morree A, Egner IM, Brett JO, Rando TA (2017) Transcriptional profiling of quiescent muscle stem cells in vivo. Cell Reports, 21: 1994-2004.

Mueller AA, van Velthoven CT, Fukumoto K, Cheung TH, Rando TA (2016) Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis. Nature, 540: 276-279.

Quarta M, Brett JO, DiMarco R, de Morree A, Boutet SC, Chacon R, Gibbons M, Garcia VA, Su J, Heilshorn S, Rando TA (2016) An artificial niche preserves the quiescence of muscle stem cells and enhances their therapeutic potential. Nature Biotechnol, 34: 752-759.

Rodgers JT, King KY, Brett JO, Cromie MJ, Charville GW, Maguire KK, Brunson C, Mastey N, Liu L, Tsai C-R, Goodell MA, Rando TA (2014) mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert. Nature, 510: 393-396.