References:
- Berdeaux R, Goebel N, Banaszynski L, Takemori H, Wandless T, Shelton GD, and Montminy M. (2007) SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes. Nat Med. 13(5): 597-603.
- Canettieri G, Koo SH, Berdeaux R, Heredia J, Hedrick S, Zhang X, Montminy M. (2005) Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling. Cell Metab. 2(5):331-8.
- Berdeaux RL, Díaz B, Kim L, Martin GS. 2004. Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function. J Cell Biol. 166(3):317-23.
- Hofer F, Berdeaux R, Martin GS. 1998. Ras-independent activation of Ral by a Ca(2+)-dependent pathway. Curr Biol. 8(14):839-42.
Rebecca Berdeaux, Ph.D.
Assistant Professor
UTHSC-H Medical School, 713-500-5653
Rebecca.Berdeaux@uth.tmc.edu
Control of gene expression
Control of gene expression is key to maintenance of tissue homeostasis in response to changing physiological conditions, such as nutrient availability, physical demands, and tissue damage. Although the role of protein phosphorylation is widely appreciated in this regard, key questions remain concerning the molecular mechanisms by which cells sense and translate such cues into transcriptional changes.
Skeletal muscle is an excellent model in which to study signal-induced transcription, as this tissue is highly organized, responds to numerous extracellular cues, and is extremely plastic. Loss of muscle homeostasis has important clinical implications, such as muscular dystrophy and cardiac hypertrophy. During physical exercise, catecholamines, such as epinephrine, induce acute effects in muscle including contraction and energy mobilization as well as sustained changes through cAMP-mediated transcription. We have recently shown that cAMP signaling induces transcription of a protein kinase called SIK1, which in turn induces expression of muscle-specific genes. We still, however, lack a detailed understanding of additional mechanisms by which cAMP, CREB, and SIK1 mediate responses of muscle to hormonal cues or structural damage and the physiological consequences of modulating these pathways in vivo. We also aim to understand more about the regulation and additional targets of SIK1.
We employ a combination of in vitro and in vivo approaches to bridge molecular mechanism with physiology. We utilize primary skeletal and cardiac myocytes as well as cultured cell lines to study molecular mechanisms of signaling with biochemical and cell biological tecnhiques such as immunoprecipitation and Western blotting, fluorescence localization assays, cell fractionation, in vitro kinase assays, real-time PCR, protein purification, microarrays and luciferase reporter assays. We also utilize in vivo models to correlate molecular mechanisms with physiological outcomes. We have several genetic mouse models, including knock-out, knock-in, and transgenic mice. In addition, we use recombinant viruses to deliver genes or RNAi sequences to tissues in living animals and are developing approaches to visualize transcription in live mice with real time imaging.
