Robert Sanders Williams | Scholars@Duke

Robert Sanders Williams
Professor 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

Professor of Medicine, Medicine, Cardiology, Medicine 2018

Contact Information

Carmichael Bldg, 300 North Duke St Room 47-205, Durham, NC 27701
Carmichael Bldg, Box 104775, Durham, NC 27701
r.s.williams@duke.edu (919) 479-2310

Background
Education, Training, & Certifications
- M.D., Duke University 1974
Duke Appointment History
- Adjunct Professor in the Department of Medicine, Medicine, Cardiology, Medicine 2010 - 2018
- 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 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
- Academic Articles
  - Williams, R Sanders, and William E. Kraus. “Exercise and health: can biotechnology confer similar benefits?.” Plos Med 2, no. 3 (March 2005). https://doi.org/10.1371/journal.pmed.0020068.
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  - Snyderman, Ralph, and R Sanders Williams. “The new prevention. Research on causes of disease must be applied to remaking our care system..” Mod Healthc 33, no. 21 (May 26, 2003).
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  - Rybkin, Igor I., David W. Markham, Zhen Yan, Rhonda Bassel-Duby, R Sanders Williams, and Eric N. Olson. “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): 15927–34. https://doi.org/10.1074/jbc.M213102200.
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  - Williams, R Sanders, Huntington F. Willard, and Ralph Snyderman. “Personalized health planning..” Science 300, no. 5619 (April 25, 2003). https://doi.org/10.1126/science.300.5619.549.
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  - Yan, Zhen, Sangdun Choi, Xuebin Liu, Mei Zhang, Jeoffrey J. Schageman, Sun Young Lee, Rebecca Hart, Ling Lin, Frederick A. Thurmond, and R Sanders Williams. “Highly coordinated gene regulation in mouse skeletal muscle regeneration..” J Biol Chem 278, no. 10 (March 7, 2003): 8826–36. https://doi.org/10.1074/jbc.M209879200.
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  - Chin, Eva R., Robert W. Grange, Francois Viau, Alain R. Simard, Caroline Humphries, John Shelton, Rhonda Bassel-Duby, R Sanders Williams, and Robin N. Michel. “Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin..” J Physiol 547, no. Pt 2 (March 1, 2003): 649–63. https://doi.org/10.1113/jphysiol.2002.024760.
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  - Vega, Rick B., Beverly A. Rothermel, Carla J. Weinheimer, Atilla Kovacs, R. H. Naseem, Rhonda Bassel-Duby, R. S. Williams, and Eric N. Olson. “Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy..” Proc Natl Acad Sci U S A 100, no. 2 (January 21, 2003): 669–74. https://doi.org/10.1073/pnas.0237225100.
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  - Rothermel, Beverly A., Rick B. Vega, and R Sanders Williams. “The role of modulatory calcineurin-interacting proteins in calcineurin signaling..” Trends Cardiovasc Med 13, no. 1 (January 2003): 15–21.
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  - Williams, R Sanders. “Another surprise from the mitochondrial genome..” N Engl J Med 347, no. 8 (August 22, 2002): 609–12. https://doi.org/10.1056/NEJMe020083.
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  - Vega, Rick B., John Yang, Beverly A. Rothermel, Rhonda Bassel-Duby, and R Sanders Williams. “Multiple domains of MCIP1 contribute to inhibition of calcineurin activity..” J Biol Chem 277, no. 33 (August 16, 2002): 30401–7. https://doi.org/10.1074/jbc.M200123200.
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  - Williams, R Sanders. “Calcineurin signaling in human cardiac hypertrophy..” Circulation 105, no. 19 (May 14, 2002): 2242–43. https://doi.org/10.1161/01.cir.0000017141.01845.fa.
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  - Wu, Hai, Shane B. Kanatous, Frederick A. Thurmond, Teresa Gallardo, Eiji Isotani, Rhonda Bassel-Duby, and R Sanders Williams. “Regulation of mitochondrial biogenesis in skeletal muscle by CaMK..” Science 296, no. 5566 (April 12, 2002): 349–52. https://doi.org/10.1126/science.1071163.
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  - Hill, Joseph A., Beverly Rothermel, Ki-Dong Yoo, Barry Cabuay, Elaine Demetroulis, Robert M. Weiss, William Kutschke, Rhonda Bassel-Duby, and R Sanders Williams. “Targeted inhibition of calcineurin in pressure-overload cardiac hypertrophy. Preservation of systolic function..” J Biol Chem 277, no. 12 (March 22, 2002): 10251–55. https://doi.org/10.1074/jbc.M110722200.
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  - Li, Kang, and R Sanders Williams. “Expression, purification, and in vitro assays of mitochondrial single-stranded DNA-binding protein..” Methods Mol Biol 197 (2002): 295–302. https://doi.org/10.1385/1-59259-284-8:295.
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  - Williams, R. S., and P. Rosenberg. “Calcium-dependent gene regulation in myocyte hypertrophy and remodeling..” Cold Spring Harb Symp Quant Biol 67 (2002): 339–44.
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  - Dunn, S. E., A. R. Simard, R. Bassel-Duby, R. S. Williams, and R. N. Michel. “Nerve activity-dependent modulation of calcineurin signaling in adult fast and slow skeletal muscle fibers..” J Biol Chem 276, no. 48 (November 30, 2001): 45243–54. https://doi.org/10.1074/jbc.M105445200.
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  - Wu, H., B. Rothermel, S. Kanatous, P. Rosenberg, F. J. Naya, J. M. Shelton, K. A. Hutcheson, et al. “Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway..” Embo J 20, no. 22 (November 15, 2001): 6414–23. https://doi.org/10.1093/emboj/20.22.6414.
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  - Grange, R. W., A. Meeson, E. Chin, K. S. Lau, J. T. Stull, J. M. Shelton, R. S. Williams, and D. J. Garry. “Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice..” Am J Physiol Cell Physiol 281, no. 5 (November 2001): C1487–94. https://doi.org/10.1152/ajpcell.2001.281.5.C1487.
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  - Kong, Y., J. M. Shelton, B. Rothermel, X. Li, J. A. Richardson, R. Bassel-Duby, and R. S. Williams. “Cardiac-specific LIM protein FHL2 modifies the hypertrophic response to beta-adrenergic stimulation..” Circulation 103, no. 22 (June 5, 2001): 2731–38. https://doi.org/10.1161/01.cir.103.22.2731.
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  - Yan, Z., A. L. Serrano, S. Schiaffino, R. Bassel-Duby, and R. S. Williams. “Regulatory elements governing transcription in specialized myofiber subtypes..” J Biol Chem 276, no. 20 (May 18, 2001): 17361–66. https://doi.org/10.1074/jbc.M101251200.
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  - Thurmond, F. A., E. M. Cronin, and R. S. Williams. “A deadly game of musical chairs: survival of cells transplanted for myocardial repair..” J Mol Cell Cardiol 33, no. 5 (May 2001): 883–85. https://doi.org/10.1006/jmcc.2001.1375.
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  - Meeson, A. P., N. Radford, J. M. Shelton, P. P. Mammen, J. M. DiMaio, K. Hutcheson, Y. Kong, J. Elterman, R. S. Williams, and D. J. Garry. “Adaptive mechanisms that preserve cardiac function in mice without myoglobin..” Circ Res 88, no. 7 (April 13, 2001): 713–20. https://doi.org/10.1161/hh0701.089753.
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  - Rothermel, B. A., T. A. McKinsey, R. B. Vega, R. L. Nicol, P. Mammen, J. Yang, C. L. Antos, et al. “Myocyte-enriched calcineurin-interacting protein, MCIP1, inhibits cardiac hypertrophy in vivo..” Proc Natl Acad Sci U S A 98, no. 6 (March 13, 2001): 3328–33. https://doi.org/10.1073/pnas.041614798.
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  - Yang, J., B. Rothermel, R. B. Vega, N. Frey, T. A. McKinsey, E. N. Olson, R. Bassel-Duby, and R. S. Williams. “Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles..” Circ Res 87, no. 12 (December 8, 2000): E61–68. https://doi.org/10.1161/01.res.87.12.e61.
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  - Zhu, W., R. S. Williams, and T. Kodadek. “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): 32098–105. https://doi.org/10.1074/jbc.M001560200.
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  - Williams, R. S., and I. J. Benjamin. “Protective responses in the ischemic myocardium..” J Clin Invest 106, no. 7 (October 2000): 813–18. https://doi.org/10.1172/JCI11205.
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  - Wren, J. D., E. Forgacs, J. W. Fondon, A. Pertsemlidis, S. Y. Cheng, T. Gallardo, R. S. Williams, R. V. Shohet, J. D. Minna, and H. R. Garner. “Repeat polymorphisms within gene regions: phenotypic and evolutionary implications..” Am J Hum Genet 67, no. 2 (August 2000): 345–56. https://doi.org/10.1086/303013.
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  - Olson, E. N., and R. S. Williams. “Calcineurin signaling and muscle remodeling..” Cell 101, no. 7 (June 23, 2000): 689–92. https://doi.org/10.1016/s0092-8674(00)80880-6.
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  - Garry, D. J., A. Meeson, Z. Yan, and R. S. Williams. “Life without myoglobin..” Cell Mol Life Sci 57, no. 6 (June 2000): 896–98. https://doi.org/10.1007/PL00000732.
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  - Olson, E. N., and R. S. Williams. “Remodeling muscles with calcineurin..” Bioessays 22, no. 6 (June 2000): 510–19. https://doi.org/10.1002/(SICI)1521-1878(200006)22:6<510::AID-BIES4>3.0.CO;2-1.
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  - Li, K., Y. Li, J. M. Shelton, J. A. Richardson, E. Spencer, Z. J. Chen, X. Wang, and R. S. Williams. “Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis..” Cell 101, no. 4 (May 12, 2000): 389–99. https://doi.org/10.1016/s0092-8674(00)80849-1.
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  - Williams, R. S. “Canaries in the coal mine: mitochondrial DNA and vascular injury from reactive oxygen species..” Circ Res 86, no. 9 (May 12, 2000): 915–16. https://doi.org/10.1161/01.res.86.9.915.
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  - Garry, D. J., A. Meeson, J. Elterman, Y. Zhao, P. Yang, R. Bassel-Duby, and R. S. Williams. “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): 5416–21. https://doi.org/10.1073/pnas.100501197.
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  - Wu, H., F. J. Naya, T. A. McKinsey, B. Mercer, J. M. Shelton, E. R. Chin, A. R. Simard, et al. “MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type..” Embo J 19, no. 9 (May 2, 2000): 1963–73. https://doi.org/10.1093/emboj/19.9.1963.
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  - Rothermel, B., R. B. Vega, J. Yang, H. Wu, R. Bassel-Duby, and R. S. Williams. “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): 8719–25. https://doi.org/10.1074/jbc.275.12.8719.
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  - Williams, R. S. “Heat shock protein 47 : a chaperone for the fibrous cap?.” Circulation 101, no. 11 (March 21, 2000): 1227–28. https://doi.org/10.1161/01.cir.101.11.1227.
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  - Williams, R. S., and P. D. Wagner. “Transgenic animals in integrative biology: approaches and interpretations of outcome..” J Appl Physiol (1985) 88, no. 3 (March 2000): 1119–26. https://doi.org/10.1152/jappl.2000.88.3.1119.
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  - Naya, F. J., B. Mercer, J. Shelton, J. A. Richardson, R. S. Williams, and E. N. Olson. “Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo..” J Biol Chem 275, no. 7 (February 18, 2000): 4545–48. https://doi.org/10.1074/jbc.275.7.4545.
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  - Yan, Z., S. A. Fedorov, M. C. Mumby, and R. S. Williams. “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): 1021–29. https://doi.org/10.1128/mcb.20.3.1021-1029.2000.
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  - Xia, Y., J. B. McMillin, A. Lewis, M. Moore, W. G. Zhu, R. S. Williams, and R. E. Kellems. “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): 1855–63. https://doi.org/10.1074/jbc.275.3.1855.
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  - Yang, Q., Y. Kong, B. Rothermel, D. J. Garry, R. Bassel-Duby, and R. S. Williams. “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): 335–43.
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  - Williams, R. S. “Apoptosis and heart failure..” N Engl J Med 341, no. 10 (September 2, 1999): 759–60. https://doi.org/10.1056/NEJM199909023411012.
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  - Williams, R. S. “Cell cycle control in the terminally differentiated myocyte. A platform for myocardial repair?.” Cardiol Clin 16, no. 4 (November 1998): 739–x.
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  - Garry, D. J., G. A. Ordway, J. N. Lorenz, N. B. Radford, E. R. Chin, R. W. Grange, R. Bassel-Duby, and R. S. Williams. “Mice without myoglobin..” Nature 395, no. 6705 (October 29, 1998): 905–8. https://doi.org/10.1038/27681.
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  - Grayson, J., R. Bassel-Duby, and R. S. Williams. “Collaborative interactions between MEF-2 and Sp1 in muscle-specific gene regulation..” J Cell Biochem 70, no. 3 (September 1, 1998): 366–75.
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  - Chin, E. R., E. N. Olson, J. A. Richardson, Q. Yang, C. Humphries, J. M. Shelton, H. Wu, W. Zhu, R. Bassel-Duby, and R. S. Williams. “A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type..” Genes Dev 12, no. 16 (August 15, 1998): 2499–2509. https://doi.org/10.1101/gad.12.16.2499.
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  - Leone, G., J. DeGregori, Z. Yan, L. Jakoi, S. Ishida, R. S. Williams, and J. R. Nevins. “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): 2120–30. https://doi.org/10.1101/gad.12.14.2120.
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  - Yan, Z., J. DeGregori, R. Shohet, G. Leone, B. Stillman, J. R. Nevins, and R. S. Williams. “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): 3603–8. https://doi.org/10.1073/pnas.95.7.3603.
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  - Schultz, R. A., S. J. Swoap, L. D. McDaniel, B. Zhang, E. C. Koon, D. J. Garry, K. Li, and R. S. Williams. “Differential expression of mitochondrial DNA replication factors in mammalian tissues..” J Biol Chem 273, no. 6 (February 6, 1998): 3447–51. https://doi.org/10.1074/jbc.273.6.3447.
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  - Neufer, P. D., G. A. Ordway, and R. S. Williams. “Transient regulation of c-fos, alpha B-crystallin, and hsp70 in muscle during recovery from contractile activity..” Am J Physiol 274, no. 2 (February 1998): C341–46. https://doi.org/10.1152/ajpcell.1998.274.2.C341.
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  - Williams, R. S. “Heat shock proteins and ischemic injury to the myocardium..” Circulation 96, no. 12 (December 16, 1997): 4138–40.
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  - Yang, Q., R. Bassel-Duby, and R. S. Williams. “Transient expression of a winged-helix protein, MNF-beta, during myogenesis..” Mol Cell Biol 17, no. 9 (September 1997): 5236–43. https://doi.org/10.1128/mcb.17.9.5236.
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  - Garry, D. J., Q. Yang, R. Bassel-Duby, and R. S. Williams. “Persistent expression of MNF identifies myogenic stem cells in postnatal muscles..” Dev Biol 188, no. 2 (August 15, 1997): 280–94. https://doi.org/10.1006/dbio.1997.8657.
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  - Li, K., and R. S. Williams. “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): 8686–94. https://doi.org/10.1074/jbc.272.13.8686.
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  - Williams, R. S., R. V. Shohet, and B. Stillman. “A human protein related to yeast Cdc6p..” Proc Natl Acad Sci U S A 94, no. 1 (January 7, 1997): 142–47. https://doi.org/10.1073/pnas.94.1.142.
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  - Neufer, P. D., G. A. Ordway, G. A. Hand, J. M. Shelton, J. A. Richardson, I. J. Benjamin, and R. S. Williams. “Continuous contractile activity induces fiber type specific expression of HSP70 in skeletal muscle..” Am J Physiol 271, no. 6 Pt 1 (December 1996): C1828–37. https://doi.org/10.1152/ajpcell.1996.271.6.C1828.
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  - Radford, N. B., M. Fina, I. J. Benjamin, R. W. Moreadith, K. H. Graves, P. Zhao, S. Gavva, et al. “Cardioprotective effects of 70-kDa heat shock protein in transgenic mice..” Proc Natl Acad Sci U S A 93, no. 6 (March 19, 1996): 2339–42. https://doi.org/10.1073/pnas.93.6.2339.
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  - Parsons, W. J., R. S. Williams, J. M. Shelton, Y. Luo, D. J. Kessler, and J. A. Richardson. “Developmental regulation of cytochrome oxidase subunit VIa isoforms in cardiac and skeletal muscle..” Am J Physiol 270, no. 2 Pt 2 (February 1996): H567–74. https://doi.org/10.1152/ajpheart.1996.270.2.H567.
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  - Garry, D. J., R. S. Bassel-Duby, J. A. Richardson, J. Grayson, P. D. Neufer, and R. S. Williams. “Postnatal development and plasticity of specialized muscle fiber characteristics in the hindlimb..” Dev Genet 19, no. 2 (1996): 146–56. https://doi.org/10.1002/(SICI)1520-6408(1996)19:2<146::AID-DVG6>3.0.CO;2-9.
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  - Li, K., P. D. Neufer, and R. S. Williams. “Nuclear responses to depletion of mitochondrial DNA in human cells..” Am J Physiol 269, no. 5 Pt 1 (November 1995): C1265–70. https://doi.org/10.1152/ajpcell.1995.269.5.C1265.
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  - Williams, R. S. “Human gene therapy--of tortoises and hares..” Nat Med 1, no. 11 (November 1995): 1137–38.
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  - Wilson, L. B., C. K. Dyke, D. Parsons, P. T. Wall, J. A. Pawelczyk, R. S. Williams, and J. H. Mitchell. “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): 1744–52. https://doi.org/10.1152/jappl.1995.79.5.1744.
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  - Li, K., and R. S. Williams. “Cloning and characterization of three new murine genes encoding short homologues of RNase P RNA..” J Biol Chem 270, no. 42 (October 20, 1995): 25281–85. https://doi.org/10.1074/jbc.270.42.25281.
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  - Williams, R. S. “American Heart Association National Research Awards. New programs for 1996..” Circulation 92, no. 2 (July 15, 1995): 152–53. https://doi.org/10.1161/01.cir.92.2.152.
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  - Grayson, J., R. S. Williams, Y. T. Yu, and R. Bassel-Duby. “Synergistic interactions between heterologous upstream activation elements and specific TATA sequences in a muscle-specific promoter..” Mol Cell Biol 15, no. 4 (April 1995): 1870–78. https://doi.org/10.1128/mcb.15.4.1870.
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  - Williams, R. S. “Boosting cardiac contractility with genes..” N Engl J Med 332, no. 12 (March 23, 1995): 817–18. https://doi.org/10.1056/NEJM199503233321212.
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  - Williams, R. S. “Cardiac involvement in mitochondrial diseases, and vice versa..” Circulation 91, no. 4 (February 15, 1995): 1266–68. https://doi.org/10.1161/01.cir.91.4.1266.
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  - Juneja, S. C., T. Pfeifer, R. S. Williams, and N. Chegini. “Neem oil inhibits two-cell embryo development and trophectoderm attachment and proliferation in vitro..” J Assist Reprod Genet 11, no. 8 (September 1994): 419–27. https://doi.org/10.1007/bf02211730.
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  - Bassel-Duby, R., M. D. Hernandez, Q. Yang, J. M. Rochelle, M. F. Seldin, and R. S. Williams. “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. https://doi.org/10.1128/mcb.14.7.4596.
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  - Michel, J. B., G. A. Ordway, J. A. Richardson, and R. S. Williams. “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): 277–85. https://doi.org/10.1172/JCI117318.
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  - Li, K., C. S. Smagula, W. J. Parsons, J. A. Richardson, M. Gonzalez, H. K. Hagler, and R. S. Williams. “Subcellular partitioning of MRP RNA assessed by ultrastructural and biochemical analysis..” J Cell Biol 124, no. 6 (March 1994): 871–82. https://doi.org/10.1083/jcb.124.6.871.
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  - Ordway, G. A., K. Li, G. A. Hand, and R. S. Williams. “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): C1511–16. https://doi.org/10.1152/ajpcell.1993.265.6.C1511.
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  - Neyses, L., J. Nouskas, J. Luyken, S. Fronhoffs, S. Oberdorf, U. Pfeifer, R. S. Williams, V. P. Sukhatme, and H. Vetter. “Induction of immediate-early genes by angiotensin II and endothelin-1 in adult rat cardiomyocytes..” J Hypertens 11, no. 9 (September 1993): 927–34.
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  - Bassel-Duby, R., C. M. Grohe, M. E. Jessen, W. J. Parsons, J. A. Richardson, R. Chao, J. Grayson, W. S. Ring, and R. S. Williams. “Sequence elements required for transcriptional activity of the human myoglobin promoter in intact myocardium..” Circ Res 73, no. 2 (August 1993): 360–66. https://doi.org/10.1161/01.res.73.2.360.
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  - Williams, R. S. “Southwestern Internal Medicine Conference: prospects for gene therapy of ischemic heart disease..” Am J Med Sci 306, no. 2 (August 1993): 129–36.
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  - Williams, R. S., J. A. Thomas, M. Fina, Z. German, and I. J. Benjamin. “Human heat shock protein 70 (hsp70) protects murine cells from injury during metabolic stress..” J Clin Invest 92, no. 1 (July 1993): 503–8. https://doi.org/10.1172/JCI116594.
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  - Parsons, W. J., J. A. Richardson, K. H. Graves, R. S. Williams, and R. W. Moreadith. “Gradients of transgene expression directed by the human myoglobin promoter in the developing mouse heart..” Proc Natl Acad Sci U S A 90, no. 5 (March 1, 1993): 1726–30. https://doi.org/10.1073/pnas.90.5.1726.
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  - Bassel-Duby, R., M. D. Hernandez, M. A. Gonzalez, J. K. Krueger, and R. S. Williams. “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): 5024–32. https://doi.org/10.1128/mcb.12.11.5024.
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  - Benjamin, I. J., S. Horie, M. L. Greenberg, R. J. Alpern, and R. S. Williams. “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): 1685–89. https://doi.org/10.1172/JCI115768.
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  - Meidell, R. S., R. D. Gerard, and R. S. Williams. “The end of the beginning. Gene transfer into the vessel wall..” Circulation 85, no. 3 (March 1992). https://doi.org/10.1161/01.cir.85.3.1219.
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  - Williams, R. S., and R. S. Meidell. “Vascular biology and invasive cardiology. The streams are beginning to merge..” Circulation 85, no. 2 (February 1992). https://doi.org/10.1161/01.cir.85.2.842.
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  - Williams, R. S., S. A. Johnston, M. Riedy, M. J. DeVit, S. G. McElligott, and J. C. Sanford. “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): 2726–30. https://doi.org/10.1073/pnas.88.7.2726.
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  - Williams, R. S., and I. J. Benjamin. “Stress proteins and cardiovascular disease..” Mol Biol Med 8, no. 2 (April 1991): 197–206.
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  - Annex, B. H., W. E. Kraus, G. L. Dohm, and R. S. Williams. “Mitochondrial biogenesis in striated muscles: rapid induction of citrate synthase mRNA by nerve stimulation..” Am J Physiol 260, no. 2 Pt 1 (February 1991): C266–70. https://doi.org/10.1152/ajpcell.1991.260.2.C266.
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  - Annex, B. H., and R. S. Williams. “Mitochondrial DNA structure and expression in specialized subtypes of mammalian striated muscle..” Mol Cell Biol 10, no. 11 (November 1990): 5671–78. https://doi.org/10.1128/mcb.10.11.5671.
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  - Williams, R. S. “Molecular biology in cardiology: recent developments and opportunities for clinical applications..” Am J Med Sci 300, no. 5 (November 1990): 304–10.
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  - Benjamin, I. J., B. Kröger, and R. S. Williams. “Activation of the heat shock transcription factor by hypoxia in mammalian cells..” Proc Natl Acad Sci U S A 87, no. 16 (August 1990): 6263–67. https://doi.org/10.1073/pnas.87.16.6263.
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  - Williams, R. S. “Genetic mechanisms that determine oxidative capacity of striated muscles. Control of gene transcription..” Circulation 82, no. 2 (August 1990): 319–31. https://doi.org/10.1161/01.cir.82.2.319.
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  - Morrow, N. G., W. E. Kraus, J. W. Moore, R. S. Williams, and J. L. Swain. “Increased expression of fibroblast growth factors in a rabbit skeletal muscle model of exercise conditioning..” J Clin Invest 85, no. 6 (June 1990): 1816–20. https://doi.org/10.1172/JCI114640.
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  - Wefald, F. C., B. H. Devlin, and R. S. Williams. “Functional heterogeneity of mammalian TATA-box sequences revealed by interaction with a cell-specific enhancer..” Nature 344, no. 6263 (March 15, 1990): 260–62. https://doi.org/10.1038/344260a0.
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  - Blumenthal, J. A., C. F. Emery, D. J. Madden, L. K. George, R. E. Coleman, M. W. Riddle, D. C. McKee, J. Reasoner, and R. S. Williams. “Cardiovascular and behavioral effects of aerobic exercise training in healthy older men and women..” J Gerontol 44, no. 5 (September 1989): M147–57.
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  - Devlin, B. H., F. C. Wefald, W. E. Kraus, T. S. Bernard, and R. S. Williams. “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): 13896–901.
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  - Kraus, W. E., T. S. Bernard, and R. S. Williams. “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): C506–14. https://doi.org/10.1152/ajpcell.1989.256.3.C506.
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  - Schachat, F., R. S. Williams, and C. A. Schnurr. “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): 13975–78.
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  - Harlan, W. R., and R. S. Williams. “Activity-induced adaptations in skeletal muscles of iron-deficient rabbits..” J Appl Physiol (1985) 65, no. 2 (August 1988): 782–87. https://doi.org/10.1152/jappl.1988.65.2.782.
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  - Blumenthal, J. A., W. J. Rejeski, M. Walsh-Riddle, C. F. Emery, H. Miller, S. Roark, P. M. Ribisl, P. B. Morris, P. Brubaker, and R. S. Williams. “Comparison of high- and low-intensity exercise training early after acute myocardial infarction..” Am J Cardiol 61, no. 1 (January 1, 1988): 26–30. https://doi.org/10.1016/0002-9149(88)91298-2.
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  - Williams, R. S., and W. Harlan. “Effects of inhibition of mitochondrial protein synthesis in skeletal muscle..” Am J Physiol 253, no. 6 Pt 1 (December 1987): C866–71. https://doi.org/10.1152/ajpcell.1987.253.6.C866.
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  - Friedman, D. B., G. A. Ordway, and R. S. Williams. “Exercise-induced functional desensitization of canine cardiac beta-adrenergic receptors..” J Appl Physiol (1985) 62, no. 4 (April 1987): 1721–23. https://doi.org/10.1152/jappl.1987.62.4.1721.
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  - Underwood, L. E., and R. S. Williams. “Pretranslational regulation of myoglobin gene expression..” Am J Physiol 252, no. 4 Pt 1 (April 1987): C450–53. https://doi.org/10.1152/ajpcell.1987.252.4.C450.
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  - Williams, R. S., M. Garcia-Moll, J. Mellor, S. Salmons, and W. Harlan. “Adaptation of skeletal muscle to increased contractile activity. Expression nuclear genes encoding mitochondrial proteins..” J Biol Chem 262, no. 6 (February 25, 1987): 2764–67.
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  - Friedman, D. B., T. I. Musch, R. S. Williams, and G. A. Ordway. “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): 124–29. https://doi.org/10.1093/cvr/21.2.124.
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  - Williams, R. S. “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): 12390–94.
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  - Schaffer, W., and R. S. Williams. “Age-dependent changes in expression of alpha 1-adrenergic receptors in rat myocardium..” Biochem Biophys Res Commun 138, no. 1 (July 16, 1986): 387–91. https://doi.org/10.1016/0006-291x(86)90293-7.
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  - Higginbotham, M. B., K. G. Morris, R. S. Williams, R. E. Coleman, and F. R. Cobb. “Physiologic basis for the age-related decline in aerobic work capacity..” Am J Cardiol 57, no. 15 (June 1, 1986): 1374–79. https://doi.org/10.1016/0002-9149(86)90221-3.
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  - Higginbotham, M. B., K. G. Morris, R. S. Williams, P. A. McHale, R. E. Coleman, and F. R. Cobb. “Regulation of stroke volume during submaximal and maximal upright exercise in normal man..” Circ Res 58, no. 2 (February 1986): 281–91. https://doi.org/10.1161/01.res.58.2.281.
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  - Williams, R. S., S. Salmons, E. A. Newsholme, R. E. Kaufman, and J. Mellor. “Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle..” J Biol Chem 261, no. 1 (January 5, 1986): 376–80.
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  - Williams, R. S. “Role of receptor mechanisms in the adaptive response to habitual exercise..” Am J Cardiol 55, no. 10 (April 26, 1985): 68D-73D. https://doi.org/10.1016/0002-9149(85)91057-4.
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  - McLeod, A. A., K. D. Knopes, D. G. Shand, and R. S. Williams. “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. https://doi.org/10.1111/j.1365-2125.1985.tb02607.x.
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  - Williams, R. S. “Exercise training of patients with ventricular dysfunction and heart failure..” Cardiovasc Clin 15, no. 2 (1985): 219–31.
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  - Williams, R. S., R. A. McKinnis, F. R. Cobb, M. B. Higginbotham, A. G. Wallace, R. E. Coleman, and R. M. Califf. “Effects of physical conditioning on left ventricular ejection fraction in patients with coronary artery disease..” Circulation 70, no. 1 (July 1984): 69–75. https://doi.org/10.1161/01.cir.70.1.69.
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  - McLeod, A. A., W. E. Kraus, and R. S. Williams. “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): 1656–61. https://doi.org/10.1016/0002-9149(84)90597-6.
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  - Shalom, R., J. A. Blumenthal, R. S. Williams, R. G. McMurray, and V. W. Dennis. “Feasibility and benefits of exercise training in patients on maintenance dialysis..” Kidney Int 25, no. 6 (June 1984): 958–63.
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  - Williams, R. S., T. F. Schaible, T. Bishop, and M. Morey. “Effects of endurance training on cholinergic and adrenergic receptors of rat heart..” J Mol Cell Cardiol 16, no. 5 (May 1984): 395–403.
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  - McLeod, A. A., J. E. Brown, B. B. Kitchell, F. A. Sedor, C. Kuhn, D. G. Shand, and R. S. Williams. “Hemodynamic and metabolic responses to exercise after adrenoceptor blockade in humans..” J Appl Physiol Respir Environ Exerc Physiol 56, no. 3 (March 1984): 716–22. https://doi.org/10.1152/jappl.1984.56.3.716.
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  - McLeod, A. A., J. E. Brown, B. B. Kitchell, F. A. Sedor, D. C. Kuhn, R. S. Williams, and D. G. Shand. “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. https://doi.org/10.1016/0002-9343(84)90964-1.
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  - Williams, R. S., M. G. Caron, and K. Daniel. “Skeletal muscle beta-adrenergic receptors: variations due to fiber type and training..” Am J Physiol 246, no. 2 Pt 1 (February 1984): E160–67. https://doi.org/10.1152/ajpendo.1984.246.2.E160.
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  - Williams, R. S., T. F. Schaible, J. Scheuer, and R. Kennedy. “Effects of experimental diabetes on adrenergic and cholinergic receptors of rat myocardium..” Diabetes 32, no. 10 (October 1983): 881–86. https://doi.org/10.2337/diab.32.10.881.
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  - McLeod, A. A., J. E. Brown, C. Kuhn, B. B. Kitchell, F. A. Sedor, R. S. Williams, and D. G. Shand. “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): 1076–84. https://doi.org/10.1161/01.cir.67.5.1076.
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  - Kopitsky, R. G., M. E. Switzer, R. S. Williams, and P. A. McKee. “The basis for the increase in factor VIII procoagulant activity during exercise..” Thromb Haemost 49, no. 1 (February 28, 1983): 53–57.
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  - Blumenthal, J. A., R. S. Williams, A. G. Wallace, R. B. Williams, and T. L. Needles. “Physiological and psychological variables predict compliance to prescribed exercise therapy in patients recovering from myocardial infarction..” Psychosom Med 44, no. 6 (December 1982): 519–27.
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  - Blumenthal, J. A., R. S. Williams, T. L. Needels, and A. G. Wallace. “Psychological changes accompany aerobic exercise in healthy middle-aged adults..” Psychosom Med 44, no. 6 (December 1982): 529–36.
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  - Williams, R. S., and T. Bishop. “Enhanced receptor-cyclase coupling and augmented catecholamine-stimulated lipolysis in exercising rats..” Am J Physiol 243, no. 5 (November 1982): E345–51. https://doi.org/10.1152/ajpendo.1982.243.5.E345.
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  - Cobb, F. R., R. S. Williams, P. McEwan, R. H. Jones, R. E. Coleman, and A. G. Wallace. “Effects of exercise training on ventricular function in patients with recent myocardial infarction..” Circulation 66, no. 1 (July 1982): 100–108. https://doi.org/10.1161/01.cir.66.1.100.
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  - Conn, E. H., R. S. Williams, and A. G. Wallace. “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. https://doi.org/10.1016/0002-9149(82)90504-5.
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  - Heyden, S., and R. S. Williams. “Cholesterol controversy--where do we go from here? 'Toward healthful diets' reevaluated..” Cardiology 69, no. 2 (1982): 110–22. https://doi.org/10.1159/000173492.
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  - Williams, R. S., R. S. Eden, M. E. Moll, R. M. Lester, and A. G. Wallace. “Autonomic mechanisms of training bradycardia: beta-adrenergic receptors in humans..” J Appl Physiol Respir Environ Exerc Physiol 51, no. 5 (November 1981): 1232–37. https://doi.org/10.1152/jappl.1981.51.5.1232.
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  - Williams, R. S., D. D. Schocken, M. Morey, and F. P. Koisch. “Medical aspects of competitive distance running: guidelines for community physicians..” Postgrad Med 70, no. 1 (July 1981): 41–51.
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  - Williams, R. S., and T. Bishop. “Selectivity of dobutamine for adrenergic receptor subtypes: in vitro analysis by radioligand binding..” J Clin Invest 67, no. 6 (June 1981): 1703–11. https://doi.org/10.1172/jci110208.
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  - Williams, R. S., and T. M. Bashore. “Paroxysmal hypotension associated with sympathetic withdrawal. A new disorder of autonomic vasomotor regulation..” Circulation 62, no. 4 (October 1980): 901–8. https://doi.org/10.1161/01.cir.62.4.901.
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  - Williams, R. S., E. E. Logue, J. G. Lewis, T. Barton, N. W. Stead, A. G. Wallace, and S. V. Pizzo. “Physical conditioning augments the fibrinolytic response to venous occlusion in healthy adults..” N Engl J Med 302, no. 18 (May 1, 1980): 987–91. https://doi.org/10.1056/NEJM198005013021802.
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  - Blumenthal, J. A., R. S. Williams, R. B. Williams, and A. G. Wallace. “Effects of exercise on the Type A (coronary prone) behavior pattern..” Psychosom Med 42, no. 2 (March 1980): 289–96.
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  - Williams, R. S. “Physical conditioning and membrane receptors for cardioregulatory hormones..” Cardiovasc Res 14, no. 3 (March 1980): 177–82. https://doi.org/10.1093/cvr/14.3.177.
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  - Williams, R. S., V. S. Behar, and R. H. Peter. “Left bundle branch block: angiographic segmental wall motion abnormalities..” Am J Cardiol 44, no. 6 (November 1979): 1046–49. https://doi.org/10.1016/0002-9149(79)90167-x.
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  - Moll, M. E., R. S. Williams, R. M. Lester, S. H. Quarfordt, and A. G. Wallace. “Cholesterol metabolism in non-obese women--Failure of physical conditioning to alter levels of high density lipoprotein cholesterol..” Atherosclerosis 34, no. 2 (October 1979): 159–66.
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  - Williams, R. S., C. E. Guthrow, and R. J. Lefkowitz. “Beta-Adrenergic receptors of human lymphocytes are unaltered by hyperthyroidism..” J Clin Endocrinol Metab 48, no. 3 (March 1979): 503–5. https://doi.org/10.1210/jcem-48-3-503.
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  - Williams, R. S., and R. J. Lefkowitz. “Alpha-adrenergic receptors in rat myocardium. Identification by binding of [3H]dihydroergocryptine..” Circ Res 43, no. 5 (November 1978): 721–27. https://doi.org/10.1161/01.res.43.5.721.
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