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Kenneth Estrellas

Class 2011
Education ScM, Brown University
ScB. Brown University
Email kestrel1@jhmi.edu
Mentor

Dr. Jennifer Elisseeff

Dr. Kathryn Wagner

Research Interests

Genetic disorders of muscles such as Duchenne Muscular Dystrophy (DMD), Facioscapulohumeral Muscular Dystrophy (FSHD), and Limb-Girdle Muscular Dystrophy (LGMD), affect hundreds of thousands of patients worldwide. DMD, the most common form of muscular dystrophy, affects 1 in 5,000 newborn males via mutation of the Dystrophin gene. Loss of the dystrophin protein leads to breakdown of the proteoglycan linkage between muscle fibers and the overlaying extracellular matrix, leading to muscular degeneration characterized by fibrosis and depletion of resident muscle progenitor cells. In patients, this results in loss of ambulation in the early teen years, and death in early adulthood due to respiratory failure and other complications.

Although there is currently no cure for DMD, as well as several of the other muscular dystrophies, a number of genetic, pharmacological, and cellular based therapies are currently in development. Inhibition of myostatin, a member of the TGF-β family, has been correlated with increased muscle growth, functional muscle regeneration, and facilitated engraftment of muscle progenitor cells. Additionally, several biomaterial-based approaches to intramuscular drug delivery have shown considerable utility in promoting the localized administration of biologics and small molecules to targeted sites within an organism, reducing off-target effects while increasing drug efficacy. Recent advances within the field of tissue engineering have described tissue-specific decellularized extracellular matrices as biocompatible scaffolds for tissue growth, with several applications tailored towards skeletal muscle. These scaffolds serve as a permissive microenvironment for cellular infiltration and proliferation, containing both architectural and biochemical cues to promote tissue regeneration. By combining advances from each of these fields, this project seeks to address the issue of genetic muscle disorders in a new way. The primary goal of this project is to develop an injectable scaffold (“hydrogel”) composed of synthetic, bioinert polymers coupled with decellularized skeletal muscle extracellular matrix to deliver myogenic growth factors and/or muscle progenitor cells to degenerating muscle, promoting functional muscle growth and regeneration, in a murine model of Duchenne Muscular Dystrophy.

Publications

  • I.Y. Choi, H.T. Lim, K.M. Estrellas, J. Mula, T.V. Cohen, Y Zhang, C.J. Donnelly, J.P Richard, Y.J. Kim, H. Kim, Y. Kazuki, M. Oshimura, H. Li, A. Hotta, J. Rothstein, N. Margakis, K.R. Wagner, G. Lee. Concordant but varied phenotypes among patient-specific myoblasts of Duchenne muscular dystrophy revealed by human iPSC-based model. Cell Reports. May 2016.
  • K.N. Sadtler, K.M. Estrellas, B.W. Allen, M.T. Wolf, H. Fan, A.J. Tam, C. Patel, B.S. Luber, H. Wang, K.R. Wagner, J.D. Powell, F. Hosseau, D.M. Pardoll, J.H. Elisseeff. Developing a Pro-Regenerative Biomaterial Scaffold Micronevironment Requires T Helper 2 Cells. Science. April 2016.