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Kenneth B. Margulies, M.D.

Professor of Medicine at the Hospital of the University of Pennsylvania
Department: Medicine
Graduate Group Affiliations

Contact information
Heart Failure and Transplant Research
Translational Research Center
3400 Civic Center Blvd, Building 421
11th floor, Room 11-101
Philadelphia, PA 19104
Philadelphia, PA 19104
Office: 215-573-2980
Fax: 215-898-3473
Education:
A.B. (Politics)
Princeton University, 1982.
M.D. (Medicine)
Jefferson Medical College, 1986.
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Description of CVI Expertise

The Margulies Lab examines mechanisms of myocardial remodeling to identify targets for therapeutic interventions. Many of our inquiries are initiated by multilevel examinations of explanted human heart tissues obtained at the time of transplantation or organ donation to permit insights into both the heterogeneity of myocardial adaptations to disease and identification of dominant mechanisms and responses. The Margulies lab has a longstanding focus on load-dependent myocardial remodeling with current studies focusing on mechanisms of load-dependent maturation, mechanical memory and pathological myocardial hypertrophy. In addition, the lab is actively engaged in studies examining regulation of contractility by microtubules and other cytoskeletal elements, cardiotoxicity associated with VEGF-anti-angiogenic tyrosine kinase inhibitors, disease-associated shifts in cardiac metabolism, mechanisms of inherited cardiomyopathies, advanced myocardial phenotyping using digital pathology and machine learning techniques, and integrated genomic inquiries designed to identify molecular mechanisms of myocardial pathology. Increasingly, complementary use of primary human cardiac myocytes, iPSC-derived cardiac myocytes and engineered cardiac microtissues are employed as versatile tools to balance human relevance and mechanistic clarity to advance these inquiries. Our work also includes, strategic patient-based proof-of-concept studies.

Selected Publications

Peyster EG, Wang C, Ishola F, Remeniuk B, Hoyt C, Feldman MD, Margulies KB.: In-situ Immune Profiling of Heart Transplant Biopsies Improves Diagnostic Accuracy and Rejection Risk Stratification. JACC Basic Transl Sci. 5(4), April 2020.

Chirinos JA, Orlenko A, Zhao L, Basso MD, Cvijic ME, Li Z, Spires TE, Yarde M, Wang Z, Seiffert DA, Prenner S, Zamani P, Bhattacharya P, Kumar A, Margulies KB, Car BD, Gordon DA, Moore JH, Cappola TP. : Multiple Plasma Biomarkers for Risk Stratification in Patients With Heart Failure and Preserved Ejection Fraction. J am Coll Cardiol. 75(11), March 2020.

Zamani P, Proto EA, Mazurek JA, Prenner SB, Margulies KB, Townsend RR, Kelly DP, Arany Z, Poole DC, Wagner PD, Chirinos JA. : Peripheral Determinants of Oxygen Utilization in Heart Failure With Preserved Ejection Fraction: Central Role of Adiposity. JACC Basic Transl Sci. 5(3), March 2020.

Cohen JB, Schrauben SJ, Zhao L, Basso MD, Cvijic ME, Li Z, Yarde M, Wang Z, Bhattacharya PT, Chirinos DA, Prenner S, Zamani P, Seiffert DA, Car BD, Gordon DA, Margulies K, Cappola T, Chirinos JA: Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone. JACC Heart Fail. January 2020.

Shah S, Henry A, Roselli C, Lin H, Sveinbjörnsson G, Fatemifar G, Hedman ÅK, Wilk JB, Morley MP, Chaffin MD, Helgadottir A, Verweij N, Dehghan A, Almgren P, Andersson C, Aragam KG, Ärnlöv J, Backman JD, Biggs ML, Bloom HL, Brandimarto J, Brown MR, Buckbinder L, Carey DJ, Chasman DI, Chen X, Chen X, Chung J, Chutkow W, Cook JP, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Dunn ME, Engström G, Esko T, Felix SB, Finan C, Ford I, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gutmann R, Haggerty CM, van der Harst P, Hyde CL, Ingelsson E, Jukema JW, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Margulies KB, März W, Melander O, Mordi IR, Morgan T, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Niessner A, Niiranen T, O'Donoghue ML, Owens AT, Palmer CNA, Parry HM, Perola M, Portilla-Fernandez E, Psaty BM; Regeneron Genetics Center, Rice KM, Ridker PM, Romaine SPR, Rotter JI, Salo P, Salomaa V, van Setten J, Shalaby AA, Smelser DT, Smith NL, Stender S, Stott DJ, Svensson P, Tammesoo ML, Taylor KD, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Trompet S, Tyl B, Uitterlinden AG, Veluchamy A, Völker U, Voors AA, Wang X, Wareham NJ, Waterworth D, Weeke PE, Weiss R, Wiggins KL, Xing H, Yerges-Armstrong LM, Yu B, Zannad F, Zhao JH, Hemingway H, Samani NJ, McMurray JJV, Yang J, Visscher PM, Newton-Cheh C, Malarstig A, Holm H, Lubitz SA, Sattar N, Holmes MV, Cappola TP, Asselbergs FW, Hingorani AD, Kuchenbaecker K, Ellinor PT, Lang CC, Stefansson K, Smith JG, Vasan RS, Swerdlow DI, Lumbers RT. : Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat Commun. 11(1), January 2020.

Caporizzo MA, Chen CY, Bedi K, Margulies KB, Prosser BL.: Microtubules Increase Diastolic Stiffness in Failing Human Cardiomyocytes and Myocardium. Circulation 2020.

Tucker NR, Chaffin M, Fleming SJ, Hall AW, Parsons VA, Bedi KC Jr, Akkad AD, Herndon CN, Arduini A, Papangeli I, Roselli C, Aguet F, Choi SH, Ardlie KG, Babadi M, Margulies KB, Stegmann CM, Ellinor PT.: Transcriptional and Cellular Diversity of the Human Heart Circulation 2020.

Chen CY, Salomon AK, Caporizzo MA, Curry S, Kelly NA, Bedi KC, Bogush AI, Krämer E, Schlossarek S, Janiak P, Moutin MJ, Carrier L, Margulies KB, Prosser BL. : Depletion of Vasohibin 1 Speeds Contraction and Relaxation in Failing Human Cardiomyocytes Circ Res 2020.

Redouane B, Greene SJ, Fudim M, aduganathan M, Ambrosy AP, Sun JL, DeVore AD, McNulty SE, Mentz RJ, Hernandez AF, Felker GM, Cooper LB, Borlaug BA, Velazquez EJ, Margulies KB, Sharma A.: Effects of Liraglutide on Worsening Renal Function Among Patients With Heart Failure With Reduced Ejection Fraction: Insights From the FIGHT Trial. Circ Heart Fail. 13(5), 2020.

Chirinos JA, Zhao L, Jia Y, Frej C, Adamo L, Mann D, Shewale SV, Millar JS, Rader DJ, French B, Brandimarto J, Margulies KB, Parks JS, Wang Z, Seiffert DA, Fang J, Sweitzer N, Chistoffersen C, Dahlbäck B, Car BD, Gordon DA, Cappola TP, Javaheri A.: Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure. Circulation 2020.

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Last updated: 11/30/2020
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