Office: South Lake Union campus, 850 Republican St., Brotman Building, Room 342, 343
We are identifying the cellular and molecular networks that governing cardiac wound healing and repair to leverage these networks as a means of developing interventions directed at enhancing repair and/or mitigating the fibrotic response.
Cellular and molecular mechanisms of cardiac wound healing and the fibrotic injury response
The impact of fibrosis and scarring on cardiac regeneration and cellular therapeutics
Signaling mechanisms govering cardiac muscle growth and remodeling
Skeletal muscle regeneration and fibrosis
The Davis lab studies how the heart heals and remodels in response to acquired and genetic diseases. Because of the heart’s limited regenerative capacity, an injury or chronic disease results in permanent fibrotic scarring, which in turn creates an environment hostile to regeneration and cellular therapies. By harnessing the power of mouse genetics, cellular engineering, genome-wide screening, and a variety of interdisciplinary experimental approaches our research is centered on elucidating the cellular and molecular underpinnings of cardiac remodeling. Specifically, this research program is focused on 3 primary areas which include (1) identifying the signaling networks causal for cardiac fibroblast differentiation into the cell-type (myofibroblast) that is causal for fibrosis and (2) manipulating the myofibroblast to improve healing after injury, and (3) identifying the mechanical signaling that determines cardiac myocyte directional growth leading to a hypertrophic or dilated heart. This research program will significantly inform the field’s understanding of fibroblast and myocyte biology as well as cardiac remodeling, which could significantly impact both drug development and the current clinical paradigms for treating acquired and genetic heart disease.
Ph.D. Molecular & Integrative Physiology, University of Michigan, Ann Arbor, 2007
M.A. Exercise & Nutritional Science, San Diego State University, 2001
B.S. Kinesiology, University of Michigan, Ann Arbor, 1996
Postdoctoral Fellow, Department of Molecular and Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center
2014 – The Louis N. & Arnold M. Katz Basic Science Research Prize from the American Heart Association honoring achievements in basic cardiovascular sciences.
Davis J, Salomonis N, Ghearing N, Lin SJ, Kwong JQ, Mohan A, Swanson MS, Molkentin JD. MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response. Nat Commun. 2015 Dec 16;6:10084. doi: 10.1038/ncomms10084. PubMed PMID: 26670661.
Goonasekera SA, Davis J*, Kwong JQ, Accornero F, Wei-LaPierre L, Sargent MA, Dirksen RT, Molkentin JD.Enhanced Ca²? influx from STIM1-Orai1 induces muscle pathology in mouse models of muscular dystrophy. Hum Mol Genet. 2014 Jul 15;23(14):3706-15. doi: 10.1093/hmg/ddu079. Epub 2014 Feb 20. PubMed PMID: 24556214; PubMed Central PMCID: PMC4065147. *, Co-first author
Wang W, Barnabei MS, Asp ML, Heinis FI, Arden E, Davis J, Braunlin E, Li Q, Davis JP, Potter JD, Metzger JM.Noncanonical EF-hand motif strategically delays Ca2+ buffering to enhance cardiac performance. Nat Med. 2013 Mar;19(3):305-12. doi: 10.1038/nm.3079. Epub 2013 Feb 10. PubMed PMID: 23396207; PubMed Central PMCID: PMC3727912.
Davis J, Kwong JQ, Kitsis RN, Molkentin JD. Apoptosis repressor with a CARD domain (ARC) restrains Bax-mediated pathogenesis in dystrophic skeletal muscle. PLoS One. 2013 Dec 2;8(12):e82053. doi: 10.1371/journal.pone.0082053. eCollection 2013. PubMed PMID: 24312627; PubMed Central PMCID: PMC3846897.
Davis J, Burr AR, Davis GF, Birnbaumer L, Molkentin JD. A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo. Dev Cell. 2012 Oct 16;23(4):705-15. doi: 10.1016/j.devcel.2012.08.017. Epub 2012 Sep 27. PubMed PMID: 23022034; PubMed Central PMCID: PMC3505601.
Kehat I, Davis J, Tiburcy M, Accornero F, Saba-El-Leil MK, Maillet M, York AJ, Lorenz JN, Zimmermann WH, Meloche S, Molkentin JD. Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth. Circ Res. 2011 Jan 21;108(2):176-83. doi: 10.1161/CIRCRESAHA.110.231514. Epub 2010 Dec 2. PubMed PMID: 21127295; PubMed Central PMCID: PMC3032171.
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