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Kenneth B. Margulies, M.D.

Kenneth B. Margulies, M.D.

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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 Research Expertise

Current Areas of Active Research in the Margulies Lab

Studies of Endogenous Cardiac Repair. We have been characterizing the immunophenotypes and capacity cardiac myocyte differentiation of resident stem cells in human hearts. We have also been studying mechanisms of stem cell engraftment to the injured heart with the goal of enhancing ordinarily poor engraftment rates observed in most clinical trials. We are collaborating on preclinical and clinical trials that are using local chemokine delivery to enhance endogenous stem cell engraftment to the heart.

Integrative Genomics of Human Heart. We are leading a consortium of three large US heart transplant centers (Penn, Stanford and Cleveland Clinic) and others that are employing existing biobanks and newly procured specimens to identify genetic variants that influence myocardial gene expression in > 1,800 normal and failing human hearts. Complementary studies will relate the results of the eQTL analysis to recent GWAS studies, define cell type-specific gene expression and examine expression profiles in human hearts with intermediate disease severity phenotypes. These studies are identifying new molecular targets for mechanistic and therapeutic studies and are establishing a durable web-based DataResource and associated BioResource consisting to allow access to the data and specimens by the scientific community.

Engineered Cardiac Microtissues (CMTs). In collaboration with Chris Chen’s Lab in Bioengineering, we are developing and optimizing mechanically loaded, functional, 3-dimensional (3D) CMTs comprised of cardiac myocytes and fibroblasts to facilitate mechanistic studies and preclinical drug screening. Microfabication techniques generate arrays of 3D CMTs embedded within silicon (PDMS) matrices and microcantilevers in the matrices simultaneously constrain CMT contraction and report forces generated by the CMTs in real time. We have generated CMTs using both neonatal rodent myocytes and human iPS-derived myocytes. Ongoing studies are examining the effects of alterations in biomechanical load, electrical stimulation, growth factors and extracellular matrix dynamics on the function and morphology of CMTs. Complementary morphological assessments and cell-type specific gene expression, secreted proteins and fluorescent reporters will be used to assess CMT maturity and the phenotypes of myocytes and fibroblasts within CMTs. We are also adapting this model for high throughput monitoring of drug-induced changes in contractility and growth.

Glucagon-Like Peptide (GLP-1) in Heart Failure. We have been examining the effects of GLP-1 in mouse models of ischemia-reperfusion and human myocardial tissues. New studies will be examining the functional effects of GLP-1 receptor gene polymorphisms. Within the NIH-sponsored Heart Failure Clinical Research Network, we are leading a phase II clinical trial of GLP-1 Agonist Therapy in patients with advanced heart failure due to systolic dysfunction.

Description of Clinical Expertise

Advanced Heart Failure and Transplant Cardiology
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Last updated: 09/18/2014
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