Robert Sanders Williams | Scholars@Duke

Robert Sanders Williams
Adjunct Professor in the Department of Medicine

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.

Current Appointments & Affiliations

Adjunct Professor in the Department of Medicine, Medicine, Cardiology, Medicine 2010

Contact Information

401 Davison Bldg, Durham, NC 27710
Box 3809 Med Ctr, Durham, NC 27710
r.s.williams@duke.edu (919) 668-0377

Background
Education, Training, & Certifications
- M.D., Duke University 1974
Duke Appointment History
- Richard and Pat Johnson University Professor of Cardiovascular Genomics, Medicine, Cardiology, Medicine 2001 - 2010
- Senior Vice Chancellor of Academic Affairs in the School of Medicine, School of Medicine, Duke University 2001 - 2010
- Professor in Pharmacology & Cancer Biology, Pharmacology & Cancer Biology, Basic Science Departments 2001 - 2008
- Dean of the School of Medicine, School of Medicine, Duke University 2001 - 2007
Recognition
Awards & Honors
- Member. Institute of Medicine of The National Academies. 2002
Research
Selected Grants
- Role of Homer Proteins in Calcium Signaling in Muscle awarded by National Institutes of Health 2005 - 2011
- Molecular Genetics of Muscle Specialization awarded by National Institutes of Health 2001 - 2009
- Exercise-Induced Mitochondrial Biogenesis awarded by National Institutes of Health 2005 - 2008
- BAA-NIH-NIAID-NCRR=DMID-03-036 (Regional Biocontainment Laboratory) awarded by National Institutes of Health 2003 - 2008
- Mentored Clinical Research Scholar Program awarded by National Institutes of Health 2002 - 2006
- General Clinical Research Center awarded by National Institutes of Health 1998 - 2006
- Duke Interdisciplinary Faculty Development in Genetics awarded by Department of Health and Human Services 2001 - 2004
- General Clinical Research Center awarded by National Institutes of Health 1975 - 2003
- Creation of a Secured IRB Protocol Management System awarded by National Institutes of Health 2002 - 2003
- Exercise And Mitochondrial Biogenesis awarded by National Institutes of Health 1989 - 1993
- Regulation Of Mitochondrial Biogenesis awarded by National Institutes of Health 1987 - 1988
- Biopsy Techniques For Adrenergic Receptor Analysis awarded by National Institutes of Health 1985 - 1986
Publications & Artistic Works
Selected Publications
- Journal Articles
  - Williams, RS, and Kraus, WE. "Exercise and health: can biotechnology confer similar benefits?." PLoS Med 2, no. 3 (March 2005): e68-. Full Text Link to Item
  - 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-. Link to Item
  - 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." J Biol Chem 278, no. 18 (May 2, 2003): 15927-15934. Full Text Link to Item
  - Williams, RS, Willard, HF, and Snyderman, R. "Personalized health planning." Science 300, no. 5619 (April 25, 2003): 549-. Full Text Link to Item
  - 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." J Biol Chem 278, no. 10 (March 7, 2003): 8826-8836. Full Text Link to Item
  - 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. Full Text Link to Item
  - 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." Proc Natl Acad Sci U S A 100, no. 2 (January 21, 2003): 669-674. Full Text Link to Item
  - 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) Link to Item
  - Williams, RS. "Another surprise from the mitochondrial genome." N Engl J Med 347, no. 8 (August 22, 2002): 609-612. Full Text Link to Item
  - Vega, RB, Yang, J, Rothermel, BA, Bassel-Duby, R, and Williams, RS. "Multiple domains of MCIP1 contribute to inhibition of calcineurin activity." J Biol Chem 277, no. 33 (August 16, 2002): 30401-30407. Full Text Link to Item
  - Williams, RS. "Calcineurin signaling in human cardiac hypertrophy." Circulation 105, no. 19 (May 14, 2002): 2242-2243. Link to Item
  - Wu, H, Kanatous, SB, Thurmond, FA, Gallardo, T, Isotani, E, Bassel-Duby, R, and Williams, RS. "Regulation of mitochondrial biogenesis in skeletal muscle by CaMK." Science 296, no. 5566 (April 12, 2002): 349-352. Full Text Link to Item
  - Hill, JA, Rothermel, B, Yoo, K-D, Cabuay, B, Demetroulis, E, Weiss, RM, Kutschke, W, Bassel-Duby, R, and Williams, RS. "Targeted inhibition of calcineurin in pressure-overload cardiac hypertrophy. Preservation of systolic function." J Biol Chem 277, no. 12 (March 22, 2002): 10251-10255. Full Text Link to Item
  - Li, K, and Williams, RS. "Expression, purification, and in vitro assays of mitochondrial single-stranded DNA-binding protein." Methods Mol Biol 197 (2002): 295-302. Full Text Link to Item
  - Williams, RS, and Rosenberg, P. "Calcium-dependent gene regulation in myocyte hypertrophy and remodeling." Cold Spring Harb Symp Quant Biol 67 (2002): 339-344. (Review) Link to Item
  - Dunn, SE, Simard, AR, Bassel-Duby, R, Williams, RS, and Michel, RN. "Nerve activity-dependent modulation of calcineurin signaling in adult fast and slow skeletal muscle fibers." J Biol Chem 276, no. 48 (November 30, 2001): 45243-45254. Full Text Link to Item
  - Wu, H, Rothermel, B, Kanatous, S, Rosenberg, P, Naya, FJ, Shelton, JM, Hutcheson, KA, DiMaio, JM, Olson, EN, Bassel-Duby, R, and Williams, RS. "Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway." EMBO J 20, no. 22 (November 15, 2001): 6414-6423. Full Text Link to Item
  - Grange, RW, Meeson, A, Chin, E, Lau, KS, Stull, JT, Shelton, JM, Williams, RS, and Garry, DJ. "Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice." Am J Physiol Cell Physiol 281, no. 5 (November 2001): C1487-C1494. Full Text Link to Item
  - Kong, Y, Shelton, JM, Rothermel, B, Li, X, Richardson, JA, Bassel-Duby, R, and Williams, RS. "Cardiac-specific LIM protein FHL2 modifies the hypertrophic response to beta-adrenergic stimulation." Circulation 103, no. 22 (June 5, 2001): 2731-2738. Link to Item
  - Yan, Z, Serrano, AL, Schiaffino, S, Bassel-Duby, R, and Williams, RS. "Regulatory elements governing transcription in specialized myofiber subtypes." J Biol Chem 276, no. 20 (May 18, 2001): 17361-17366. Full Text Link to Item
  - Thurmond, FA, Cronin, EM, and Williams, RS. "A deadly game of musical chairs: survival of cells transplanted for myocardial repair." J Mol Cell Cardiol 33, no. 5 (May 2001): 883-885. Full Text Link to Item
  - Meeson, AP, Radford, N, Shelton, JM, Mammen, PP, DiMaio, JM, Hutcheson, K, Kong, Y, Elterman, J, Williams, RS, and Garry, DJ. "Adaptive mechanisms that preserve cardiac function in mice without myoglobin." Circ Res 88, no. 7 (April 13, 2001): 713-720. Link to Item
  - Rothermel, BA, McKinsey, TA, Vega, RB, Nicol, RL, Mammen, P, Yang, J, Antos, CL, Shelton, JM, Bassel-Duby, R, Olson, EN, and Williams, RS. "Myocyte-enriched calcineurin-interacting protein, MCIP1, inhibits cardiac hypertrophy in vivo." Proc Natl Acad Sci U S A 98, no. 6 (March 13, 2001): 3328-3333. Full Text Link to Item
  - Yang, J, Rothermel, B, Vega, RB, Frey, N, McKinsey, TA, Olson, EN, Bassel-Duby, R, and Williams, RS. "Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles." Circ Res 87, no. 12 (December 8, 2000): E61-E68. Link to Item
  - Zhu, W, Williams, RS, and Kodadek, T. "A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system is a cell cycle inhibitor." J Biol Chem 275, no. 41 (October 13, 2000): 32098-32105. Full Text Link to Item
  - Williams, RS, and Benjamin, IJ. "Protective responses in the ischemic myocardium." J Clin Invest 106, no. 7 (October 2000): 813-818. (Review) Full Text Link to Item
  - Wren, JD, Forgacs, E, Fondon, JW, Pertsemlidis, A, Cheng, SY, Gallardo, T, Williams, RS, Shohet, RV, Minna, JD, and Garner, HR. "Repeat polymorphisms within gene regions: phenotypic and evolutionary implications." Am J Hum Genet 67, no. 2 (August 2000): 345-356. Full Text Link to Item
  - Olson, EN, and Williams, RS. "Calcineurin signaling and muscle remodeling." Cell 101, no. 7 (June 23, 2000): 689-692. (Review) Link to Item
  - Garry, DJ, Meeson, A, Yan, Z, and Williams, RS. "Life without myoglobin." Cell Mol Life Sci 57, no. 6 (June 2000): 896-898. (Review) Full Text Link to Item
  - Olson, EN, and Williams, RS. "Remodeling muscles with calcineurin." Bioessays 22, no. 6 (June 2000): 510-519. (Review) Full Text Link to Item
  - Li, K, Li, Y, Shelton, JM, Richardson, JA, Spencer, E, Chen, ZJ, Wang, X, and Williams, RS. "Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis." Cell 101, no. 4 (May 12, 2000): 389-399. Link to Item
  - Williams, RS. "Canaries in the coal mine: mitochondrial DNA and vascular injury from reactive oxygen species." Circ Res 86, no. 9 (May 12, 2000): 915-916. (Review) Link to Item
  - Garry, DJ, Meeson, A, Elterman, J, Zhao, Y, Yang, P, Bassel-Duby, R, and Williams, RS. "Myogenic stem cell function is impaired in mice lacking the forkhead/winged helix protein MNF." Proc Natl Acad Sci U S A 97, no. 10 (May 9, 2000): 5416-5421. Full Text Link to Item
  - Wu, H, Naya, FJ, McKinsey, TA, Mercer, B, Shelton, JM, Chin, ER, Simard, AR, Michel, RN, Bassel-Duby, R, Olson, EN, and Williams, RS. "MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type." EMBO J 19, no. 9 (May 2, 2000): 1963-1973. Full Text Link to Item
  - Rothermel, B, Vega, RB, Yang, J, Wu, H, Bassel-Duby, R, and Williams, RS. "A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling." J Biol Chem 275, no. 12 (March 24, 2000): 8719-8725. Link to Item
  - Williams, RS. "Heat shock protein 47 : a chaperone for the fibrous cap?." Circulation 101, no. 11 (March 21, 2000): 1227-1228. (Review) Link to Item
  - Williams, RS, and Wagner, PD. "Transgenic animals in integrative biology: approaches and interpretations of outcome." J Appl Physiol (1985) 88, no. 3 (March 2000): 1119-1126. (Review) Full Text Link to Item
  - Naya, FJ, Mercer, B, Shelton, J, Richardson, JA, Williams, RS, and Olson, EN. "Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo." J Biol Chem 275, no. 7 (February 18, 2000): 4545-4548. Link to Item
  - Yan, Z, Fedorov, SA, Mumby, MC, and Williams, RS. "PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells." Mol Cell Biol 20, no. 3 (February 2000): 1021-1029. Link to Item
  - Xia, Y, McMillin, JB, Lewis, A, Moore, M, Zhu, WG, Williams, RS, and Kellems, RE. "Electrical stimulation of neonatal cardiac myocytes activates the NFAT3 and GATA4 pathways and up-regulates the adenylosuccinate synthetase 1 gene." J Biol Chem 275, no. 3 (January 21, 2000): 1855-1863. Link to Item
  - Yang, Q, Kong, Y, Rothermel, B, Garry, DJ, Bassel-Duby, R, and Williams, RS. "The winged-helix/forkhead protein myocyte nuclear factor beta (MNF-beta) forms a co-repressor complex with mammalian sin3B." Biochem J 345 Pt 2 (January 15, 2000): 335-343. Link to Item
  - Williams, RS. "Apoptosis and heart failure." N Engl J Med 341, no. 10 (September 2, 1999): 759-760. (Review) Full Text Link to Item
  - Williams, RS. "Cell cycle control in the terminally differentiated myocyte. A platform for myocardial repair?." Cardiol Clin 16, no. 4 (November 1998): 739-x. (Review) Link to Item
  - Garry, DJ, Ordway, GA, Lorenz, JN, Radford, NB, Chin, ER, Grange, RW, Bassel-Duby, R, and Williams, RS. "Mice without myoglobin." Nature 395, no. 6705 (October 29, 1998): 905-908. Full Text Link to Item
  - Grayson, J, Bassel-Duby, R, and Williams, RS. "Collaborative interactions between MEF-2 and Sp1 in muscle-specific gene regulation." J Cell Biochem 70, no. 3 (September 1, 1998): 366-375. Link to Item
  - Chin, ER, Olson, EN, Richardson, JA, Yang, Q, Humphries, C, Shelton, JM, Wu, H, Zhu, W, Bassel-Duby, R, and Williams, RS. "A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type." Genes Dev 12, no. 16 (August 15, 1998): 2499-2509. Link to Item
  - Leone, G, DeGregori, J, Yan, Z, Jakoi, L, Ishida, S, Williams, RS, and Nevins, JR. "E2F3 activity is regulated during the cell cycle and is required for the induction of S phase." Genes Dev 12, no. 14 (July 15, 1998): 2120-2130. Link to Item
  - Yan, Z, DeGregori, J, Shohet, R, Leone, G, Stillman, B, Nevins, JR, and Williams, RS. "Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells." Proc Natl Acad Sci U S A 95, no. 7 (March 31, 1998): 3603-3608. Link to Item
  - Schultz, RA, Swoap, SJ, McDaniel, LD, Zhang, B, Koon, EC, Garry, DJ, Li, K, and Williams, RS. "Differential expression of mitochondrial DNA replication factors in mammalian tissues." J Biol Chem 273, no. 6 (February 6, 1998): 3447-3451. Link to Item
  - Neufer, PD, Ordway, GA, and Williams, RS. "Transient regulation of c-fos, alpha B-crystallin, and hsp70 in muscle during recovery from contractile activity." Am J Physiol 274, no. 2 Pt 1 (February 1998): C341-C346. Link to Item
  - Williams, RS. "Heat shock proteins and ischemic injury to the myocardium." Circulation 96, no. 12 (December 16, 1997): 4138-4140. (Review) Link to Item
  - Yang, Q, Bassel-Duby, R, and Williams, RS. "Transient expression of a winged-helix protein, MNF-beta, during myogenesis." Mol Cell Biol 17, no. 9 (September 1997): 5236-5243. Link to Item
  - Garry, DJ, Yang, Q, Bassel-Duby, R, and Williams, RS. "Persistent expression of MNF identifies myogenic stem cells in postnatal muscles." Dev Biol 188, no. 2 (August 15, 1997): 280-294. Full Text Link to Item
  - Li, K, and Williams, RS. "Tetramerization and single-stranded DNA binding properties of native and mutated forms of murine mitochondrial single-stranded DNA-binding proteins." J Biol Chem 272, no. 13 (March 28, 1997): 8686-8694. Link to Item
  - Williams, RS, Shohet, RV, and Stillman, B. "A human protein related to yeast Cdc6p." Proc Natl Acad Sci U S A 94, no. 1 (January 7, 1997): 142-147. Link to Item
  - Neufer, PD, Ordway, GA, Hand, GA, Shelton, JM, Richardson, JA, Benjamin, IJ, and Williams, RS. "Continuous contractile activity induces fiber type specific expression of HSP70 in skeletal muscle." Am J Physiol 271, no. 6 Pt 1 (December 1996): C1828-C1837. Full Text Link to Item
  - Radford, NB, Fina, M, Benjamin, IJ, Moreadith, RW, Graves, KH, Zhao, P, Gavva, S, Wiethoff, A, Sherry, AD, Malloy, CR, and Williams, RS. "Cardioprotective effects of 70-kDa heat shock protein in transgenic mice." Proc Natl Acad Sci U S A 93, no. 6 (March 19, 1996): 2339-2342. Link to Item
  - Parsons, WJ, Williams, RS, Shelton, JM, Luo, Y, Kessler, DJ, and Richardson, JA. "Developmental regulation of cytochrome oxidase subunit VIa isoforms in cardiac and skeletal muscle." Am J Physiol 270, no. 2 Pt 2 (February 1996): H567-H574. Full Text Link to Item
  - Garry, DJ, Bassel-Duby, RS, Richardson, JA, Grayson, J, Neufer, PD, and Williams, RS. "Postnatal development and plasticity of specialized muscle fiber characteristics in the hindlimb." Dev Genet 19, no. 2 (1996): 146-156. Full Text Link to Item
  - Li, K, Neufer, PD, and Williams, RS. "Nuclear responses to depletion of mitochondrial DNA in human cells." Am J Physiol 269, no. 5 Pt 1 (November 1995): C1265-C1270. Full Text Link to Item
  - Williams, RS. "Human gene therapy--of tortoises and hares." Nat Med 1, no. 11 (November 1995): 1137-1138. Link to Item
  - Wilson, LB, Dyke, CK, Parsons, D, Wall, PT, Pawelczyk, JA, Williams, RS, and Mitchell, JH. "Effect of skeletal muscle fiber type on the pressor response evoked by static contraction in rabbits." J Appl Physiol (1985) 79, no. 5 (November 1995): 1744-1752. Full Text Link to Item
  - Li, K, and Williams, RS. "Cloning and characterization of three new murine genes encoding short homologues of RNase P RNA." J Biol Chem 270, no. 42 (October 20, 1995): 25281-25285. Link to Item
  - Williams, RS. "American Heart Association National Research Awards. New programs for 1996." Circulation 92, no. 2 (July 15, 1995): 152-153. Link to Item
  - Grayson, J, Williams, RS, Yu, YT, and Bassel-Duby, R. "Synergistic interactions between heterologous upstream activation elements and specific TATA sequences in a muscle-specific promoter." Mol Cell Biol 15, no. 4 (April 1995): 1870-1878. Link to Item
  - Williams, RS. "Boosting cardiac contractility with genes." N Engl J Med 332, no. 12 (March 23, 1995): 817-818. Full Text Link to Item
  - Williams, RS. "Cardiac involvement in mitochondrial diseases, and vice versa." Circulation 91, no. 4 (February 15, 1995): 1266-1268. Link to Item
  - Juneja, SC, Pfeifer, T, Williams, RS, and Chegini, N. "Neem oil inhibits two-cell embryo development and trophectoderm attachment and proliferation in vitro." J Assist Reprod Genet 11, no. 8 (September 1994): 419-427. Link to Item
  - Bassel-Duby, R, Hernandez, MD, Yang, Q, Rochelle, JM, Seldin, MF, and Williams, RS. "Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes." Mol Cell Biol 14, no. 7 (July 1994): 4596-4605. Link to Item
  - Michel, JB, Ordway, GA, Richardson, JA, and Williams, RS. "Biphasic induction of immediate early gene expression accompanies activity-dependent angiogenesis and myofiber remodeling of rabbit skeletal muscle." J Clin Invest 94, no. 1 (July 1994): 277-285. Full Text Link to Item
  - Li, K, Smagula, CS, Parsons, WJ, Richardson, JA, Gonzalez, M, Hagler, HK, and Williams, RS. "Subcellular partitioning of MRP RNA assessed by ultrastructural and biochemical analysis." The Journal of cell biology 124, no. 6 (March 1994): 871-882. Full Text
  - Ordway, GA, Li, K, Hand, GA, and Williams, RS. "RNA subunit of mitochondrial RNA-processing enzyme is induced by contractile activity in striated muscle." Am J Physiol 265, no. 6 Pt 1 (December 1993): C1511-C1516. Full Text Link to Item
  - Neyses, L, Nouskas, J, Luyken, J, Fronhoffs, S, Oberdorf, S, Pfeifer, U, Williams, RS, Sukhatme, VP, and Vetter, H. "Induction of immediate-early genes by angiotensin II and endothelin-1 in adult rat cardiomyocytes." J Hypertens 11, no. 9 (September 1993): 927-934. Link to Item
  - Bassel-Duby, R, Grohe, CM, Jessen, ME, Parsons, WJ, Richardson, JA, Chao, R, Grayson, J, Ring, WS, and Williams, RS. "Sequence elements required for transcriptional activity of the human myoglobin promoter in intact myocardium." Circulation research 73, no. 2 (August 1993): 360-366. Full Text
  - Williams, RS. "Southwestern Internal Medicine Conference: prospects for gene therapy of ischemic heart disease." Am J Med Sci 306, no. 2 (August 1993): 129-136. Link to Item
  - Williams, RS, Thomas, JA, Fina, M, German, Z, and Benjamin, IJ. "Human heat shock protein 70 (hsp70) protects murine cells from injury during metabolic stress." J Clin Invest 92, no. 1 (July 1993): 503-508. Full Text Link to Item
  - Parsons, WJ, Richardson, JA, Graves, KH, Williams, RS, and Moreadith, RW. "Gradients of transgene expression directed by the human myoglobin promoter in the developing mouse heart." Proceedings of the National Academy of Sciences of the United States of America 90, no. 5 (March 1993): 1726-1730. Full Text
  - Bassel-Duby, R, Hernandez, MD, Gonzalez, MA, Krueger, JK, and Williams, RS. "A 40-kilodalton protein binds specifically to an upstream sequence element essential for muscle-specific transcription of the human myoglobin promoter." Mol Cell Biol 12, no. 11 (November 1992): 5024-5032. Link to Item
  - Benjamin, IJ, Horie, S, Greenberg, ML, Alpern, RJ, and Williams, RS. "Induction of stress proteins in cultured myogenic cells. Molecular signals for the activation of heat shock transcription factor during ischemia." J Clin Invest 89, no. 5 (May 1992): 1685-1689. Full Text Link to Item
  - Meidell, RS, Gerard, RD, and Williams, RS. "The end of the beginning. Gene transfer into the vessel wall." Circulation 85, no. 3 (March 1992): 1219-. Link to Item
  - Williams, RS, and Meidell, RS. "Vascular biology and invasive cardiology. The streams are beginning to merge." Circulation 85, no. 2 (February 1992): 842-. Link to Item
  - Williams, RS, Johnston, SA, Riedy, M, DeVit, MJ, McElligott, SG, and Sanford, JC. "Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles." Proc Natl Acad Sci U S A 88, no. 7 (April 1, 1991): 2726-2730. Link to Item
  - Williams, RS, and Benjamin, IJ. "Stress proteins and cardiovascular disease." Mol Biol Med 8, no. 2 (April 1991): 197-206. (Review) Link to Item
  - Annex, BH, Kraus, WE, Dohm, GL, and Williams, RS. "Mitochondrial biogenesis in striated muscles: rapid induction of citrate synthase mRNA by nerve stimulation." Am J Physiol 260, no. 2 Pt 1 (February 1991): C266-C270. Full Text Link to Item
  - Annex, BH, and Williams, RS. "Mitochondrial DNA structure and expression in specialized subtypes of mammalian striated muscle." Mol Cell Biol 10, no. 11 (November 1990): 5671-5678. Link to Item
  - Williams, RS. "Molecular biology in cardiology: recent developments and opportunities for clinical applications." Am J Med Sci 300, no. 5 (November 1990): 304-310. Link to Item
  - Benjamin, IJ, Kröger, B, and Williams, RS. "Activation of the heat shock transcription factor by hypoxia in mammalian cells." Proc Natl Acad Sci U S A 87, no. 16 (August 1990): 6263-6267. Link to Item
  - Williams, RS. "Genetic mechanisms that determine oxidative capacity of striated muscles. Control of gene transcription." Circulation 82, no. 2 (August 1990): 319-331. (Review) Link to Item
  - Morrow, NG, Kraus, WE, Moore, JW, Williams, RS, and Swain, JL. "Increased expression of fibroblast growth factors in a rabbit skeletal muscle model of exercise conditioning." J Clin Invest 85, no. 6 (June 1990): 1816-1820. Full Text Link to Item
  - Wefald, FC, Devlin, BH, and Williams, RS. "Functional heterogeneity of mammalian TATA-box sequences revealed by interaction with a cell-specific enhancer." Nature 344, no. 6263 (March 15, 1990): 260-262. Full Text Link to Item
  - Blumenthal, JA, Emery, CF, Madden, DJ, George, LK, Coleman, RE, Riddle, MW, McKee, DC, Reasoner, J, and Williams, RS. "Cardiovascular and behavioral effects of aerobic exercise training in healthy older men and women." J Gerontol 44, no. 5 (September 1989): M147-M157. Link to Item
  - Devlin, BH, Wefald, FC, Kraus, WE, Bernard, TS, and Williams, RS. "Identification of a muscle-specific enhancer within the 5'-flanking region of the human myoglobin gene." J Biol Chem 264, no. 23 (August 15, 1989): 13896-13901. Link to Item
  - Kraus, WE, Bernard, TS, and Williams, RS. "Interactions between sustained contractile activity and beta-adrenergic receptors in regulation of gene expression in skeletal muscles." Am J Physiol 256, no. 3 Pt 1 (March 1989): C506-C514. Full Text Link to Item
  - Schachat, F, Williams, RS, and Schnurr, CA. "Coordinate changes in fast thin filament and Z-line protein expression in the early response to chronic stimulation." J Biol Chem 263, no. 28 (October 5, 1988): 13975-13978. Link to Item
  - Harlan, WR, and Williams, RS. "Activity-induced adaptations in skeletal muscles of iron-deficient rabbits." J Appl Physiol (1985) 65, no. 2 (August 1988): 782-787. Full Text Link to Item
  - Blumenthal, JA, Rejeski, WJ, Walsh-Riddle, M, Emery, CF, Miller, H, Roark, S, Ribisl, PM, Morris, PB, Brubaker, P, and Williams, RS. "Comparison of high- and low-intensity exercise training early after acute myocardial infarction." Am J Cardiol 61, no. 1 (January 1, 1988): 26-30. Link to Item
  - Williams, RS, and Harlan, W. "Effects of inhibition of mitochondrial protein synthesis in skeletal muscle." Am J Physiol 253, no. 6 Pt 1 (December 1987): C866-C871. Full Text Link to Item
  - Friedman, DB, Ordway, GA, and Williams, RS. "Exercise-induced functional desensitization of canine cardiac beta-adrenergic receptors." J Appl Physiol (1985) 62, no. 4 (April 1987): 1721-1723. Full Text Link to Item
  - Underwood, LE, and Williams, RS. "Pretranslational regulation of myoglobin gene expression." Am J Physiol 252, no. 4 Pt 1 (April 1987): C450-C453. Full Text Link to Item
  - Williams, RS, Garcia-Moll, M, Mellor, J, Salmons, S, and Harlan, W. "Adaptation of skeletal muscle to increased contractile activity. Expression nuclear genes encoding mitochondrial proteins." J Biol Chem 262, no. 6 (February 25, 1987): 2764-2767. Link to Item
  - Friedman, DB, Musch, TI, Williams, RS, and Ordway, GA. "Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta 2 adrenoceptors in the sinoatrial node." Cardiovasc Res 21, no. 2 (February 1987): 124-129. Link to Item
  - Williams, RS. "Mitochondrial gene expression in mammalian striated muscle. Evidence that variation in gene dosage is the major regulatory event." J Biol Chem 261, no. 26 (September 15, 1986): 12390-12394. Link to Item
  - Schaffer, W, and Williams, RS. "Age-dependent changes in expression of alpha 1-adrenergic receptors in rat myocardium." Biochem Biophys Res Commun 138, no. 1 (July 16, 1986): 387-391. Link to Item
  - Higginbotham, MB, Morris, KG, Williams, RS, Coleman, RE, and Cobb, FR. "Physiologic basis for the age-related decline in aerobic work capacity." Am J Cardiol 57, no. 15 (June 1, 1986): 1374-1379. Link to Item
  - Higginbotham, MB, Morris, KG, Williams, RS, McHale, PA, Coleman, RE, and Cobb, FR. "Regulation of stroke volume during submaximal and maximal upright exercise in normal man." Circ Res 58, no. 2 (February 1986): 281-291. Link to Item
  - Williams, RS, Salmons, S, Newsholme, EA, Kaufman, RE, and Mellor, J. "Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle." J Biol Chem 261, no. 1 (January 5, 1986): 376-380. Link to Item
  - Williams, RS. "Role of receptor mechanisms in the adaptive response to habitual exercise." Am J Cardiol 55, no. 10 (April 26, 1985): 68D-73D. Link to Item
  - McLeod, AA, Knopes, KD, Shand, DG, and Williams, RS. "Beta 1-selective and non-selective beta-adrenoceptor blockade, anaerobic threshold and respiratory gas exchange during exercise." Br J Clin Pharmacol 19, no. 1 (January 1985): 13-20. Link to Item
  - Williams, RS. "Exercise training of patients with ventricular dysfunction and heart failure." Cardiovasc Clin 15, no. 2 (1985): 219-231. (Review) Link to Item
  - Williams, RS, McKinnis, RA, Cobb, FR, Higginbotham, MB, Wallace, AG, Coleman, RE, and Califf, RM. "Effects of physical conditioning on left ventricular ejection fraction in patients with coronary artery disease." Circulation 70, no. 1 (July 1984): 69-75. Link to Item
  - McLeod, AA, Kraus, WE, and Williams, RS. "Effects of beta 1-selective and nonselective beta-adrenoceptor blockade during exercise conditioning in healthy adults." Am J Cardiol 53, no. 11 (June 1, 1984): 1656-1661. Link to Item
  - Shalom, R, Blumenthal, JA, Williams, RS, McMurray, RG, and Dennis, VW. "Feasibility and benefits of exercise training in patients on maintenance dialysis." Kidney Int 25, no. 6 (June 1984): 958-963. Link to Item
  - Williams, RS, Schaible, TF, Bishop, T, and Morey, M. "Effects of endurance training on cholinergic and adrenergic receptors of rat heart." J Mol Cell Cardiol 16, no. 5 (May 1984): 395-403. Link to Item
  - McLeod, AA, Brown, JE, Kitchell, BB, Sedor, FA, Kuhn, C, Shand, DG, and Williams, RS. "Hemodynamic and metabolic responses to exercise after adrenoceptor blockade in humans." J Appl Physiol Respir Environ Exerc Physiol 56, no. 3 (March 1984): 716-722. Full Text Link to Item
  - McLeod, AA, Brown, JE, Kitchell, BB, Sedor, FA, Kuhn, DC, Williams, RS, and Shand, DG. "Hemodynamic and metabolic responses to exercise after alpha 1-, beta 1-, and nonselective beta-adrenoceptor blockade in man." Am J Med 76, no. 2A (February 27, 1984): 97-100. Link to Item
  - Williams, RS, Caron, MG, and Daniel, K. "Skeletal muscle beta-adrenergic receptors: variations due to fiber type and training." Am J Physiol 246, no. 2 Pt 1 (February 1984): E160-E167. Full Text Link to Item
  - Williams, RS, Schaible, TF, Scheuer, J, and Kennedy, R. "Effects of experimental diabetes on adrenergic and cholinergic receptors of rat myocardium." Diabetes 32, no. 10 (October 1983): 881-886. Link to Item
  - McLeod, AA, Brown, JE, Kuhn, C, Kitchell, BB, Sedor, FA, Williams, RS, and Shand, DG. "Differentiation of hemodynamic, humoral and metabolic responses to beta 1- and beta 2-adrenergic stimulation in man using atenolol and propranolol." Circulation 67, no. 5 (May 1983): 1076-1084. Link to Item
  - Kopitsky, RG, Switzer, ME, Williams, RS, and McKee, PA. "The basis for the increase in factor VIII procoagulant activity during exercise." Thromb Haemost 49, no. 1 (February 28, 1983): 53-57. Link to Item
  - Blumenthal, JA, Williams, RS, Needels, TL, and Wallace, AG. "Psychological changes accompany aerobic exercise in healthy middle-aged adults." Psychosom Med 44, no. 6 (December 1982): 529-536. Link to Item
  - Blumenthal, JA, Williams, RS, Wallace, AG, Williams, RB, and Needles, TL. "Physiological and psychological variables predict compliance to prescribed exercise therapy in patients recovering from myocardial infarction." Psychosom Med 44, no. 6 (December 1982): 519-527. Link to Item
  - Williams, RS, and Bishop, T. "Enhanced receptor-cyclase coupling and augmented catecholamine-stimulated lipolysis in exercising rats." Am J Physiol 243, no. 5 (November 1982): E345-E351. Full Text Link to Item
  - Cobb, FR, Williams, RS, McEwan, P, Jones, RH, Coleman, RE, and Wallace, AG. "Effects of exercise training on ventricular function in patients with recent myocardial infarction." Circulation 66, no. 1 (July 1982): 100-108. Link to Item
  - Conn, EH, Williams, RS, and Wallace, AG. "Exercise responses before and after physical conditioning in patients with severely depressed left ventricular function." Am J Cardiol 49, no. 2 (February 1, 1982): 296-300. Link to Item
  - Heyden, S, and Williams, RS. "Cholesterol controversy--where do we go from here? 'Toward healthful diets' reevaluated." Cardiology 69, no. 2 (1982): 110-122. Full Text Link to Item
  - Williams, RS, Eden, RS, Moll, ME, Lester, RM, and Wallace, AG. "Autonomic mechanisms of training bradycardia: beta-adrenergic receptors in humans." J Appl Physiol Respir Environ Exerc Physiol 51, no. 5 (November 1981): 1232-1237. Full Text Link to Item
  - Williams, RS, Schocken, DD, Morey, M, and Koisch, FP. "Medical aspects of competitive distance running: guidelines for community physicians." Postgrad Med 70, no. 1 (July 1981): 41-51. Link to Item
  - Williams, RS, and Bishop, T. "Selectivity of dobutamine for adrenergic receptor subtypes: in vitro analysis by radioligand binding." J Clin Invest 67, no. 6 (June 1981): 1703-1711. Link to Item
  - Williams, RS, and Bashore, TM. "Paroxysmal hypotension associated with sympathetic withdrawal. A new disorder of autonomic vasomotor regulation." Circulation 62, no. 4 (October 1980): 901-908. Link to Item
  - Williams, RS, Logue, EE, Lewis, JG, Barton, T, Stead, NW, Wallace, AG, and Pizzo, SV. "Physical conditioning augments the fibrinolytic response to venous occlusion in healthy adults." N Engl J Med 302, no. 18 (May 1, 1980): 987-991. Full Text Link to Item
  - Blumenthal, JA, Williams, RS, Williams, RB, and Wallace, AG. "Effects of exercise on the Type A (coronary prone) behavior pattern." Psychosom Med 42, no. 2 (March 1980): 289-296. Link to Item
  - Williams, RS. "Physical conditioning and membrane receptors for cardioregulatory hormones." Cardiovasc Res 14, no. 3 (March 1980): 177-182. Link to Item
  - Williams, RS, Behar, VS, and Peter, RH. "Left bundle branch block: angiographic segmental wall motion abnormalities." Am J Cardiol 44, no. 6 (November 1979): 1046-1049. Link to Item
  - Moll, ME, Williams, RS, Lester, RM, Quarfordt, SH, and Wallace, AG. "Cholesterol metabolism in non-obese women--Failure of physical conditioning to alter levels of high density lipoprotein cholesterol." Atherosclerosis 34, no. 2 (October 1979): 159-166. Link to Item
  - Williams, RS, Guthrow, CE, and Lefkowitz, RJ. "Beta-Adrenergic receptors of human lymphocytes are unaltered by hyperthyroidism." J Clin Endocrinol Metab 48, no. 3 (March 1979): 503-505. Full Text Link to Item
  - Williams, RS, and Lefkowitz, RJ. "Alpha-adrenergic receptors in rat myocardium. Identification by binding of [3H]dihydroergocryptine." Circ Res 43, no. 5 (November 1978): 721-727. Link to Item

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Education, Training, & Certifications

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