Jeffery D. Molkentin, Ph.D.

Research

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.