Dr. Rebecca Berdeaux
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Integrative Biology and Pharmacology
Signal-dependent transcription in metabolic tissues
Most mammalian tissues are highly adaptive to changing physiological states. Extracellular cues or signals not only prompt immediate adjustments within cells in seconds or minutes, but also frequently initiate longer-term responses through induction or repression of gene expression. Signal-dependent transcription is a particularly important means by which metabolically active tissues adapt to changing nutrient availability, physical demands and even acute tissue damage. Our laboratory studies one such transcriptional pathway activated by hormonal signaling through the second messenger cAMP to the transcription factor CREB. One of the genes induced by CREB in many tissues is a serine/ threonine kinase called SIK1 (salt inducible kinase 1). SIK1, in turn, either feeds back to inhibit CREB or feeds forward to promote activity of other transcription factors, such as the myocyte enhancer factor MEF2.
We hypothesize that SIK1 is temporally regulated by transcriptional and post-translational mechanisms to allow appropriate physiologic responses in liver and skeletal muscle. Moreover, we posit that dysregulated SIK1 activity could contribute to pathophysiologic states including type 2 diabetes and muscle damage after injury or during aging. Using biochemical approaches and mouse genetics, we are currently investigating regulation and function of SIK1 in both organ systems, with an aim of better defining general and tissue-selective mechanisms of SIK1 regulation in vivo.
Located within the thriving Texas Medical Center, our laboratory and department are equipped with state-of-the art instrumentation for phenotypic analysis of mice and tissues, confocal microscopy, in vivo bioluminescence reporter imaging in mice, and biochemical assays of cellular signaling. We study cell signaling in primary hepatocytes and myoblasts and develop unique transgenic mouse models to rigorously test our hypotheses.
Graduate students admitted to the Graduate School of Biomedical Sciences at The University of Texas Health Science Center Houston may perform tutorial rotations and subsequently pursue coursework and a thesis project through the Biochemistry & Cell Biology Program.
Keywords: Physiology, skeletal muscle, exercise, muscle, signaling, insulin, diabetes, cAMP