Robert Sanders Williams, MD

Professor of Medicine
Campus mail Carmichael Bldg, 300 North Duke St Room 47-205, Durham, NC 27701
Phone (919) 479-2310
Email address r.s.williams@duke.edu

The Williams lab seeks to discover fundamental mechanisms of cell regulation pertinent to human health and disease, and to develop technologies that are applicable to clinical medicine. Recent progress has included the characterization of novel proteins and pathways that modulate proliferation and differentiation of myogenic stem cells, hypertrophic growth of the heart, mitochondrial biogenesis and fiber type-specific gene expression in skeletal muscles.

A particularly successful line of recent investigation has focused on calcium-dependent gene regulation in myocyte hypertrophy and remodeling.
Striated myocytes from skeletal and cardiac muscle tissues are excitable cells that utilize calcium to trigger actomyosin cross-bridge formation in the generation of contractile force. Myocytes respond to different temporal patterns of activation and changing workloads by altering programs of gene expression that adjust cellular mass, kinetic properties of contractile proteins, and metabolic capacity to match muscle phenotypes to different physiological demands. In disease states, modulation of gene expression in myocytes as a function of contractile workload may have maladaptive consequences. We have considered the general hypothesis that changes in intracellular calcium resulting from different patterns of contractile activity serve not only to drive muscle contractions, but provide a primary stimulus to activity-dependent changes in gene expression and muscle phenotype. Accordingly, we have investigated the role of calcium-regulated signaling molecules in controlling transcription of genes that are subject to activity-dependent regulation. Using cultured myocytes and transgenic mouse models, we have defined features of signaling cascades that modulate transcription of specific contractile protein isoforms, mitochondrial biogenesis, and myocyte mass. These pathways involve calmodulin-dependent protein kinases, the calcium-calmodulin regulated protein phosphatase calcineurin, transcription factors of the MEF-2, NF-AT, and PGC-1 families, and proteins of the MCIP (DSCR1) gene family. Calcium released from discrete intracellular and extracellular pools exerts different effects on the kinetics of activation of specific transcription factors in striated myocytes. Our findings support a conceptual model for activity-dependent gene regulation in myocytes.

Education and Training

  • M.D., Duke University, 1974

Publications

Williams, RS, and Kraus, WE. "Exercise and health: can biotechnology confer similar benefits?." PLoS Med 2, no. 3 (March 2005): e68-.

PMID
15783257
Full Text

Snyderman, R, and Williams, RS. "The new prevention. Research on causes of disease must be applied to remaking our care system." Mod Healthc 33, no. 21 (May 26, 2003): 19-.

PMID
12800288
Scholars@Duke

Rybkin, II, Markham, DW, Yan, Z, Bassel-Duby, R, Williams, RS, and Olson, EN. "Conditional expression of SV40 T-antigen in mouse cardiomyocytes facilitates an inducible switch from proliferation to differentiation." The Journal of Biological Chemistry 278, no. 18 (May 2003): 15927-15934.

PMID
12590133
Full Text

Williams, RS, Willard, HF, and Snyderman, R. "Personalized health planning." Science 300, no. 5619 (April 25, 2003): 549-.

PMID
12714710
Full Text

Chin, ER, Grange, RW, Viau, F, Simard, AR, Humphries, C, Shelton, J, Bassel-Duby, R, Williams, RS, and Michel, RN. "Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin." J Physiol 547, no. Pt 2 (March 1, 2003): 649-663.

PMID
12562945
Full Text

Yan, Z, Choi, S, Liu, X, Zhang, M, Schageman, JJ, Lee, SY, Hart, R, Lin, L, Thurmond, FA, and Williams, RS. "Highly coordinated gene regulation in mouse skeletal muscle regeneration." The Journal of Biological Chemistry 278, no. 10 (March 2003): 8826-8836.

PMID
12477723
Full Text

Vega, RB, Rothermel, BA, Weinheimer, CJ, Kovacs, A, Naseem, RH, Bassel-Duby, R, Williams, RS, and Olson, EN. "Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy." Proceedings of the National Academy of Sciences of the United States of America 100, no. 2 (January 6, 2003): 669-674.

PMID
12515860
Full Text

Rothermel, BA, Vega, RB, and Williams, RS. "The role of modulatory calcineurin-interacting proteins in calcineurin signaling." Trends Cardiovasc Med 13, no. 1 (January 2003): 15-21. (Review)

PMID
12554096
Scholars@Duke

Williams, RS. "Another surprise from the mitochondrial genome." N Engl J Med 347, no. 8 (August 22, 2002): 609-612.

PMID
12192023
Full Text

Vega, RB, Yang, J, Rothermel, BA, Bassel-Duby, R, and Williams, RS. "Multiple domains of MCIP1 contribute to inhibition of calcineurin activity." The Journal of Biological Chemistry 277, no. 33 (August 2002): 30401-30407.

PMID
12063245
Full Text

Pages