Lance Dworkin investigates the pathogenesis of progression of chronic kidney disease, including factors that modulate renal fibrosis and scarring, and renal inflammation, which are invariable findings in kidneys progressing to end stage renal failure. He is also the study chair for the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, a large multicenter randomized clinical trial funded by the National Heart, Lung, and Blood Institute (NHLBI) that is examining the best therapy for patients with hypertension due to atherosclerotic renal vascular disease.

Biography

Lance D. Dworkin, M.D., is Professor of Medicine, Vice Chairman of Medicine for Research, Academic Affairs and Ethics, and Director of the Division of Kidney Disease & Hypertension at Brown Medical School. He earned his undergraduate degree at Yale and his M.D. degree at the University of Pennsylvania. He completed residency training and was chief medical resident at New York University/Bellevue Hospital. He trained in nephrology at Brigham & Women's Hospital, Harvard University. He was Associate Professor of Medicine and Associate Medical Director of the Clinical Research Center at New York University until 1993 when he moved to Brown. Dr. Dworkin conducts research on the mechanisms of progressive kidney failure and its prevention and on the treatment of renovascular hypertension. He is the author of over 100 original articles, reviews, book chapters and has been an invited lecturer at numerous academic medical centers and scientific meetings in the United States and abroad.

Institutions

Rih

Research Description

Lance Dworkin, M.D., serves as director of nephrology at Rhode Island Hospital and is a lead investigator in an effort to identify the role of hepatocyte growth factor (HGF) in chronic renal injury. In collaboration with Rujun Gong, he directs studies examining the effects of HGF on the molecular mechanism(s) governing matrix synthesis and degradation and in renal epithelial cells as they relate to renal fibrosis and scarring. Gong and Dworkin are also examining the role of HGF in modulating renal inflammation and the inflammatory phenotype in renal epithelial and endothelial cells. Interstitial inflammation is an invariable finding in kidneys progressing to end stage renal failure, and interventions that modulate this inflammatory response may lead to novel therapies to help slow progression of chronic renal disease. They are also investigating the significance of endothelial dysfunction as a key contributor to renal disease progression. They hypothesize that endothelial cells generate inflammatory cytokines that then promote inflammation and kidney injury. Studies in vivo have been extended to an in vitro model system of bovine glomerular endothelial cells in culture where the pathological cascades involved in endothelial cell dysfunction can be systematically studied.

As a clinical investigator, Lance Dworkin also directs a clinical trials program examining the treatment of various forms of hypertension and dyslipidemia. He is currently the study chair and senior leader for the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study, a large multicenter clinical trial funded by the National Heart, Lung, and Blood Institute (NHLBI) that will compare angioplasty and stenting plus optimal medical therapy to medical therapy alone for the treatment of atherosclerotic renal artery stenosis. This study will enroll approximately 1100 patients at up to 100 centers across the United States. Other recent or current clinical trials have examined the impact of various antihypertensive agents or lipid lowering drugs on cardiovascular outcomes in patients with hypertension and/or chronic renal disease.

Awards

National Research Service Award, National Institutes of Health, 1980, 1981
New Investigator Award, National Institutes of Health, 1984-1987
Career Scientist Award, Irma T. Hirschl Trust, 1985-1990
Grant-In-Aid, American Heart Association, 1992, 1998
Specialist in Clinical Hypertension, American Society of Hypertension, 1999-present
Who's Who in America, 2000-present
Brown Medical School Dean's Teaching Excellence Award, Bio 301 Clerkship in Medicine, 2001
Brown Medical School Dean's Teaching Excellence Awards, Bio 281 Pathophysiology/Renal, 2003-2010
American Heart Association, Fellow of the Council on the Kidney in Cardiovascular Disease, F.A.H.A., 2003
American Society of Nephrology, Fellow, 2004
Best Doctors of America, 2005-2010
Beckwith Family Award for Outstanding Teaching, Department of Medicine, Alpert Medical School of Brown University, 2010
Honorary Professor, Jinling Hospital, Nanjing University School of Clinical Medicine, Nanjing, China, 2007-2010
Robert Schrier Award of the International Society of Nephrology for Sister Renal Center Program with Research Institute of Nephrology, Jingling Hospital, Nanjing University, Nanjing China, 2011

Affiliations

American Association for Advancement of Sciences, 1996-present
American College of Physicians/American Society of Internal Medicine, Fellow, 2002-present
American Federation for Clinical Research, 1984-present
American Heart Association, Council on Hypertension, FAHA, 1988-present
American Society of Hypertension, 1986-present
American Society of Nephrology, FASN, 1982-present
International Society of Nephrology, 1988-present
National Kidney Foundation, 1994-present
New York Society of Nephrology, 1984-1993, President 1991
Renal Physicians Association, 1998-present
Association of Professors of Medicine, 2006-present

Funded Research

1. Project Title: Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL)
Role: Principal Investigator (Study Chair)
Sponsoring Agency: National Institute of Health
Period of Support: 5/1/04-4/30/10
Amount of Support: $534,535

2. Project Title: A randomized controlled trial of mycophenolate mofetil in patients with Iga nephropathy
Role: Principal Investigator
Sponsoring Agency: Medical City Dallas Hospital
Period of Support: 12/2/02-
Amount of Support: $30,000

3. Project Title: A randomized, double-blind, placebo-controlled, parallel group evaluation of the effects of lipid-lowering therapy with Simvastatin and Ezetimibe compared with placebo on time to a first cardiovascular event
Role: Principal Investigator
Sponsoring Agency: University of Oxford
Period of Support: 2/10/04-1/31/09
Amount of Support: $30,000

Teaching Experience

Dr. Dworkin is a small group leader for the renal pathophysiology section of Biomed 281. He is the course director for the renal elective at Rhode Island Hospital. He serves as attending physician supervising renal fellows, residents and medical students on the various inpatient services of the Division of Renal Diseases at Rhode Island Hospital, The Miriam Hospital and The Veterans Administration Hospital. He serves as medical attending on the Medicine A teaching service supervising medical residents and students. He is a frequent lecturer to renal fellows, medical residents and students on various topics in nephrology at multiple affiliated hospitals. He has presented at multiple Medical and Renal Grand Rounds conferences.

Courses Taught

• renal pathophysiology (BIO281)

View My Full Publication List in pdf format

Selected Publications

• 31. Dworkin, LD. Controversial treatment of renal artery stenosis. Hypertension, E-pub, 2006(2006)
• 29.Yango AF, Gohh, RY, Monaco AP, Reinhart S, Gautam AP, Dworkin LD, Morrisey PE. Excess risk of renal allograft loss and early mortality among elderly recipients associated with poor exercise capacity. Clin Neph, 65:401-407, June, 2006.(2006)
• 28. Gong R, Rifai A, Dworkin LD. Hepatocyte growth factor suppresses acute renal inflammation by inhibition of endothelial E-selectin. Kidney Int, 69(7):1166-1174, April, 2006.(2006)
• 30. Cooper, CJ, Murphy TP, Matusomoto A, Steffes M, Cohen DJ, Jaff M, Kuntz R, Jamerson K, Reid D, Rosenfield K, Rundback J, D'Agostino R, Henrich W, Dworkin LD. Stent revascularization for the prevention of cardiovascular and renal events among patients with renal artery stenosis and systolic hypertension: Rationale and design of the CORAL trial. Am Heart J, 152(1):59-66, July, 2006(2006)
• 26. Gong R, Rifai A, Dworkin LD. Activation of PI3K-Akt-GSK3beta pathway mediates HGF inhibition of RANTES expression in renal tubular epithelial cells. Biochem Biophys Res Commun, 330(1):27-33, April, 2005.(2005)
• 25. Biswas P, Roy A, Gong R, Yango A, Tolbert E, Centracchio J, Dworkin LD. HGF induces an endothelin mediated decline in GFR. Am J of Physiol, Renal Physiol; 288(1):F8-F15, January, 2005(2005)
• 27. Murphy TP, Cooper CJ, Dworkin LD, Henrich WL, Rundback JH, Matsumoto AH, Jamerson KA, D'Agostino RB. The Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) Study: rationale and methods. J Vasc Interv Radiol. 16(10):1295-1300, October, 2005.(2005)
• 24. Gong R, Rifai A, Tolbert EM, Centracchio JN, Dworkin LD. HGF ameliorates renal interstitial inflammation in nephrectomized rats by modulating the tubular expression of MCP-1 and RANTES., J Am Soc Neph, 15:2868-2881, October, 2004.(2004)
• 23. Dworkin LD, Gong R, Tolbert E, Centracchio J, Yano N, Zanabli A, Esparza A, Rifai A. HGF ameliorates progession of interstitial fibrosis in rats with established renal injury. Kidney International, 65(2):409-419, February, 2004.(2004)
• 22. Gong R, Rifai A, Tolbert E, Centracchio J, Dworkin LD. HGF modulates matrix metallaproteinases and plasminogen activator/plamin proteolytic pathways in progressive renal interstitial fibrosis. J Am Soc Neph, 14:3047-3060, December, 2003(2003)
• 21. Yango A, Morrisey P, Zanabli A, Beaulieu, J, Shemin D, Dworkin LD, Monaco A, Gohh R. Comparative Study of Prophylactic Oral Gancyclovir and Valcyclovir in high-risk kidney transplant recipients. Nephrol Dial Transplant, 18:1-5, January, 2003(2003)
• 19. Yano N, Fadden-Paiva K, Endoh M, Sakai H, Kurokawa K, Dworkin LD, Rifai A. Profiling the IgA nephropathy renal transcriptome: analysis by complementary DNA array hybridization. Nephrology, 7:S140-S144, August, 2002(2002)
• 18. Gandor H, Bagley PJ, Shemin D, Hsu N, Jacques PF, Dworkin LD, Bostom AG, Selhub J. Daily distribution of plasma folate forms in hemodialysis patients receiving high doses of L-folinic or folic acid. Kidney International, 62:2246-2249, 2002.(2002)
• 20. Yango A, Morrissey P, Monaco A, Gohh R, Centracchio J, Dworkin LD. Renal Production of HGF increases after unilateral nephrectomy in man. Transplant Proceedings, 34(8):3128-3129, December, 2002.(2002)
• 17. Bostom AG, Shemin D, Gohh RY, Beaulieu AJ, Bagley P, Massey ZA, Jacques PF, Dworkin LD, Selhub J. Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients. Kidney International, 59(Supp 78):S246-S252, 2001.(2001)
• 15. Yango A, Shemin D, Hsu N, Jacques PF, Dworkin LD, Selhub J, Bostom AG. L-folinic acid vs. folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients. Kidney International, 59:324-327, 2001.(2001)
• 16. Shemin D, Bostom AG, Laliberty P, Dworkin LD. Residual renal function and mortality risk in hemodialysis patients. Am J Kidney Disease, 38:85-90, 2001.(2001)
• 14. Bostom AG, Shemin D, Bagley P, Massy Z, Zanabli A, Christopher K, Spiegel P, Jacques PF, Dworkin LD, Selhub J. Controlled Comparison of L-5-Methyltetrahyrofolate Versus Folic Acid for the Treatment of Hyperhomocysteinemia in Hemodialysis Patients. Circulation, 101:2829-2832, 2000.(2000)
• 13. Bostom AG, Dworkin LD. Cystatin C Measurement Improved Detection of Mild Decrements in Glomerular Filtration Rate Versus Certificate-Based Estimates? Am J of Kidney Disease, 36:205-207, 2000.(2000)
• 12. Liu Y, Rajur K, Tolbert E, Dworkin LD. Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways. Kidney International, 58:5. 2028-2043, November, 2000.(2000)
• 10. Bostom AG, Shemin D, Gohh RY, Beaulieu AJ, Jacques PF, Dworkin LD, Selhub J. Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients. Transplantation, 68:10, 1-4, 2000.(2000)
• 11. Tolbert E, Weisttuch J, Finer H, Dworkin LD. Onset of glomerular hypertension with aging precedes injury in the spontaneously hypertensive rat. AJP:Renal Physiology, 278:F839-F846, May, 2000.(2000)
• 9. Bostom AG, Gohh RY, Liagaudas G, Beaulieu AJ, Han H, Jacques PF, Dworkin LD, Rosenberg IH, Selhub J: Prevalence of mild fasting hyperhomocysteinemia in renal transplant versus coronary artery disease after fortification of cereal grain flour with folic acid.Atherosclerosis, 145:221-224, 1999.(1999)
• 8. Bostom AG, Gohh RY, Beaulieu AJ, Han H, Jacques PF, Selhub J, Dworkin LD, Rosenberg IH. Determinants of fasting plasma total homocysteine levels among stable renal transplant recipients in the era of folic acid fortified cereal grain flour. Transplantation. 62:257-261, 1999.(1999)
• 7. Beaulieu AJ, Laplane KL, Gohh RY, Selhub J, Monaco AP, Dworkin LD, Rosenberg IH, and Bostom AG. Short-term reproducibility of total homocysteine determinations in stable renal transplant recipients. Transplant Proceedings. 31:2121-2123, 1999.(1999)
• 6. Shemin D, Laplane K, Bausserman L, Kanaan E, Kahan S, Dworkin LD, and Bostom A. Plasma total homocysteine and hemodialysis access thrombosis: A prospective study. J Am Soc Nephrol. 10:1095-1099, 1999.(1999)
• 5. Bostom AG, Gohh RY, Bausserman L, Hakas D, Jacques PF, Selhub , Dworkin LD. Serum cystatin C as a determinant of fasting total homocysteine levels in renal transplant recipients with a normal serum creatinine. J Am Soc Nephrol. 10:164-166, 1999.(1999)
• 4. Liu Y, Tolbert EM, Lin L, Thursby MA, Sun AM, Nakamura T, Dworkin LD. Up-regulation of hepatocyte growth factor receptor: An amplification and targeting mechanism for hepatocyte growth factor action in acute renal failure. Kidney Int. 55:442-453, 1999.(1999)
• 2. Sun AM, Liu Y, Centracchio J, Dworkin LD. Expression of Na+/H+ exchanger isoforms in terminal inner medullary collecting duct (IMCDt). J Membrane Biol, 164:293-300, 1998.(1998)
• 1. Liu Y, Centracchio J, Lin L, Sun AM, Dworkin LD. Constitutive expression of HGF modulates renal epithelial cell phenotypes and induces c-met and fibronectin expression. Exp Cell Res. 242:174-185, 1998.(1998)
• 3. Liu Y, Sun AM, Dworkin LD. Hepatocyte growth factor proctects renal epithelial cells from apoptotic death. Biochem Biophy Res Commun, 246:821-826, 1998.(1998)