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Research Overview

Dr. Kunkel’s research uses mouse and zebrafish models of the muscular dystrophies to develop a better understanding of the human disorders and develop rational therapies.

Laboratory Projects

  1. miRNAs in Duchenne Dystrophy:Using array based screening, miRNAs that are dysregulated in human muscular dystrophy were identified and the laboratory is testing whether manipulation of specific miRNAs might be therapeutic.

  2. Jagged1 as a genetic modifier of dystrophin deficiency:The laboratory has used genomic approaches to characterize a dog model of dystrophin deficiency, which escapes the consequences of this deficiency. Jagged1 was identified as being elevated 2.5 fold in expression level in these dogs and when jagged1 is increased in our zebrafish model it also ameliorated symptoms. We are currently working in collaboration with Pfizer to identify small molecules, which might increase levels and be of therapeutic benefit to patients.

  3. Characterization of DUX4 in facioscapulohumeral muscular dystrophy (FSHD):DUX4 is a transcription factor, which is miss-regulated in FSHD and the laboratory is attempting to model this disorder in Zebrafish. We are also using CRISPR-Cas9 technology to identify genes whose inactivation will lead to resistance to DUX4 toxicity and might be a genetic modifier of disease severity.

Research Background

Dr. Louis Kunkel is an internationally recognized geneticist with years of experience and scientific success in the understanding of the basis for muscular dystrophies. He received a B.A. from Gettysburg College and his Ph.D. from Johns Hopkins University. Over the past three decades Dr. Kunkel has devoted his career to understanding the molecular basis, and developing therapy, for neuromuscular disorders. Dr. Kunkel is universally recognized for his 1986 identification of dystrophin as the causative gene in Duchenne muscular dystrophy. His current work centers on developing dystrophin independent therapies for Duchenne muscular dystrophy to complement existing therapies currently in development. He has received numerous awards for his research including membership to the National Academy of Sciences and The American Academy of Arts and Sciences. Dr. Kunkel recently received the 2009 March of Dimes Prize in Developmental Biology for this pioneering work on muscular dystrophy. He leads a long-standing effort to develop novel therapies.

Selected Publications

  1. Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987 Dec 24;51(6):919-28. PubMed PMID: 3319190.
  2. Kawahara G, Karpf JA, Myers JA, Alexander MS, Guyon JR, Kunkel LM. Drug screening in a zebrafish model of Duchenne muscular dystrophy. Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5331-6. doi: 10.1073/pnas.1102116108. Epub 2011 Mar 14. PubMed PMID: 21402949; PubMed Central PMCID: PMC3069215.
  3. Mitsuhashi H, Mitsuhashi S, Lynn-Jones T, Kawahara G, Kunkel LM. Expression of DUX4 in zebrafish development recapitulates facioscapulohumeral muscular dystrophy. Hum Mol Genet. 2013 Feb 1; 22(3):568-77. doi: 10.1093/hmg/dds467. Epub 2012 Oct 29. PMC3606007
  4. Alexander MS, Casar JC, Motohashi N, Vieira NM, Eisenberg I, Marshall JL, Gasperini MJ, Lek A, Myers JA, Estrella EA, Kang PB, Shapiro F, Rahimov F, Kawahara G, Widrick JJ, Kunkel LM. MicroRNA-486-dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy-associated symptoms. J Clin Invest. 2014 Jun 2;124(6):2651-67. doi: 10.1172/JCI73579. Epub 2014 May 1. PMC4038577
  5. Vieira NM, Elvers, Alexander MS, Moreira YB, Eran A, Gomes JP, Marshall JL, Karlsson EK,Verjovski-Almeida S, Lindblad-Toh K, Kunkel LM, Zatz M (2015). Jagged 1 Rescues the Duchenne Muscular Dystrophy Phenotype. Cell 2015 Nov 19; 163(5): 1204-13 doi: 10.1016/j.cell.2015. 10.049. PMCID: PMC4668935

Publications