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Kenneth B. Margulies, MD

Kenneth B. Margulies, MD Physician

Research Director, Heart Failure/ Transplantation
Professor of Medicine at the Hospital of the University of Pennsylvania
Professor of Physiology

Dr. Margulies is a Penn Medicine employed physician.

Clinical Specialties

Specialty:

  • Medicine
    • Cardiology

Programs & Centers:

Board Certification:

  • Advanced Heart Failure and Transplant Cardiology, 2010
  • Internal Medicine, 1989

Clinical Expertise:

  • Heart Transplant - Orthotopic
  • Heart Transplant - Post-Transplant Follow-Up
  • Heart Transplant Evaluation
  • Heart Transplantation

Description of Clinical Expertise

Advanced Heart Failure and Transplant Cardiology

Practice Locations and Appointments

Insurance Accepted

  • Aetna US Healthcare
  • Cigna
  • Cigna HealthSpring
  • Devon Health Services (Americare)
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Medicaid
  • PA Medicare
  • Preferred Health Care/LGH
  • Rail Road Medicare / Palmetto GBA
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan

Education and Training

Medical School: Jefferson Medical College
Residency: Mayo Clinic
Fellowship: Mayo Clinic

Memberships

American College of Cardiology, National American Federation for Clinical Research, National American Heart Association, National American Heart Association, National American Society of Clinical Investigation, National Committee on Academic Freedom and Responsibility, National Heart Failure Society of America, National Heart Failure Society of America, National International Society of Heart and Lung Transplantation, International National Institutes of Health, National

Hospital Affiliation

Dr. Margulies is a Penn Medicine employed physician.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.
  • Penn Medicine Rittenhouse Long-Term Acute Care Hospital: Has privileges to treat patients in the hospital.

Research

Description of Research Expertise:

Current Areas of Active Research in the Margulies Lab

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. Ongoing studies include further characterizations of samples with RNA sequencing and integration with DNA and histone methylation and digital pathology characterizations.

Engineered Cardiac Microtissues (CMTs). In collaboration with faculty from Penn's School of Engineering and Applied Science, 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.

Studies of Myocardial Metabolism in Heart Failure. These studies include metabolomic profiling of human heart tissues from patient with and without heart failure and patients with and without diabetes mellitus. Studies are identifying novel shifts in cardiac substrate utilization that may alter regulatory pathyways relavent to metabolism and other processes. A separate line of inquiry with Dr. Florin Despa's laboratory at the University of Kentucky has been examining the role of islet-derived amylin polypeptides and oligomers as contributors to target organ (heart, kidney, brain) dysfunction in patients with type-2 diabetes mellitus. In clinical studies, 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.

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.

Academic Contact Info

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
Phone: (215) 573-2980
Fax: (215) 898-3473
Patient appointments: 800-789-PENN (7366)

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