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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

Corbin EA, Vite A, Peyster EG, Bhoopalam M, Brandimarto J, Wang X, Bennett AI, Clark AT, Cheng X, Turner KT, Musunuru K, Margulies KB: Tunable and Reversible Substrate Stiffness Reveals a Dynamic Mechanosensitivity of Cardiomyocytes. ACS Appl Mater Interfaces 11(23): 20603-20614, June 2019.

Morley MP, Wang X, Hu R, Brandimarto J, Tucker NR, Felix JF, Smith NL, van der Harst P, Ellinor PT, Margulies KB, Musunuru K, Cappola TP: Cardioprotective Effects of MTSS1 Enhancer Variants. Circulation 139(17): 2073-2076, April 2019.

Xiong Y, Bedi KC, Berritt S, Brooks TG, Attipoe BK, Wang K, Margulies KB, Field J: Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays disease onset. JCI Insight March 2019.

Moyes AJ, Chu SM, Aubdool AA, Dukinfield MS, Margulies KB, Bedi KC, Hodivala-Dilke K, Baliga RS, Hobbs AJ: C-type natriuretic peptide co-ordinates cardiac structure and function. Eur Heart J March 2019.

Blackstone EH, Chang HL, Rajeswaran J, Parides MK, Ishwaran H, Li L, Ehrlinger J, Gelijns AC, Moskowitz AJ, Argenziano M, DeRose JJ Jr, Couderc JP, Balda D, Dagenais F, Mack MJ, Ailawadi G, Smith PK, Acker MA, O'Gara PT, Gillinov AM; Cardiothoracic Surgical Trials Network Investigators: Biatrial maze procedure versus pulmonary vein isolation for atrial fibrillation during mitral valve surgery: New analytical approaches and end points. J Thorac Cardiovasc Surg 157(1): 234-243, January 2019.

Sharma A, Ambrosy AP, DeVore AD, Margulies KB, McNulty SE, Mentz RJ, Hernandez AF, Michael Felker G, Cooper LB, Lala A, Vader J, Groake JD, Borlaug BA, Velazquez EJ: Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial. ESC Heart Fail Aug 2018

Chen CY, Caporizzo MA, Bedi K, Vite A, Bogush AI, Robison P, Heffler JG, Salomon AK, Kelly NA, Babu A, Morley MP, Margulies KB, Prosser BL: Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure. Nat Med Jun 2018

Nirschl JJ, Janowczyk A, Peyster EG, Frank R, Margulies KB, Feldman MD, Madabhushi A: A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue. PLoS One 3;13 (4), Apr 2018

Baggio LL, Yusta B, Mulvihill EE, Cao X, Streutker CJ, Butany J, Cappola TP, Margulies KB, Drucker DJ: GLP-1 receptor expression within the human heart. Endocrinology Feb 2018

Birati EY, Hanff TC, Maldonado D, Grandin EW, Kennel PJ, Mazurek JA, Vorovich E, Seigerman M, Howard JLL, Acker MA, Naka Y, Wald J, Goldberg LR, Jessup M, Atluri P, Margulies KB, Schulze PC, Rame JE: Predicting Long Term Outcome in Patients Treated With Continuous Flow Left Ventricular Assist Device: The Penn-Columbia Risk Score. J Am Heart Assoc 2018

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Last updated: 06/13/2019
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