Jeff Molkentin
Jeff 
Molkentin
, Ph.D.
Professor

B.S. , Marquette University

Ph.D. , Medical College of Wisconsin

Postdoc. , University of Texas-Southwestern

The laboratory is interested in understanding the intracellular signaling pathways and transcriptional regulatory circuits that control mammalian cell growth and differentiation. In response to various growth factors or stress stimuli, discrete signal transduction pathways are activated at the cell membrane and within the cytoplasm that subsequently modify the activity of key transcription factors resulting in the reprogramming of gene expression. Important model systems for the investigation of growth and stress responses include cardiac myocytes, skeletal muscle myocytes, and T lymphocytes. The laboratory is specifically interested in characterizing signal transduction through the calcium-activated phosphatase calcineurin and the downstream transcriptional effector protein NFAT. Calcineurin directly dephosphorylates NFAT transcription factors allowing their nuclear import as a mechanism of inducible gene regulation in cardiac and skeletal muscle cells and T cells. We are also interested in mitogen-activated protein kinase (MAPK) signaling pathways and their role in altering gene expression in mammalian cells. The laboratory uses transgenic mouse models and gene knock-out technology towards dissecting intracellular signaling pathways and transcriptional regulatory factors, as well as routine molecular approaches.


Selected Publications:
  • Oka T, Maillet M, Watt AJ, Schwartz RJ, Aronow BJ, Duncan SA, Molkentin JD. (2006) Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circ. Res. 98:837-845.
  • Sanna B, Brandt EB, Kaiser RA, Pfluger P, Witt SA, Kimball TR, van Rooij E, De Windt LJ, Rothenberg ME, Tschop MH, Benoit SC, Molkentin JD. (2006) Modulatory calcineurin interacting proteins 1 and 2 function as calcineurin facilitators in vivo. Proc. Natl. Acad. Sci. USA. 103:7327-7332.
  • Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD. (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658-662.
  • Dai Y-S, Xu J, Molkentin JD. (2005) The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells (NFAT) and mediates transcriptional repression through class II histone deacetylase (HDAC) recruitment. Mol. Cell. Biol. 25:9936-9948.
  • Braz JC, Gregory K, Pathak A, Zhao W, Sahin B, Klevitsky R, Kimball1 TF, Lorenz JN, Nairn AC, Liggett SB, Iodi B, Wang S, Schwartz A, Lakatta EG, DePaoli-Roach AA, Robbins J, Hewett TE, Bibb JA, Westfall MV, Kranias EG, Molkentin JD. (2004) PKCalpha regulates cardiac contractility and propensity towards heart failure. Nat. Med. 10:248-254.


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