Stacey Rentschler, MD, PhD

Research interests

Developmental programming and reprogramming of conduction tissue

The cardiac conduction system arises from lineage specification of cardiomyocyte progenitors and functions to generate and propagate electrical impulses within the heart.  Our laboratory is seeking to identify the signaling pathways that instruct cardiomyocytes to become conduction cells during normal development. In addition, we have demonstrated that activation of the Notch signaling pathways at later stages of maturation can reprogram differentiated cardiomyocytes into conduction-like cells. Deciphering the signals that instruct cells to adopt a conduction phenotype may ultimately provide insight into regenerative approaches, such as the development of a biologic pacemaker.

Molecular basis of congenital heart defects

Congenital heart defects, including those that give rise to conduction disorders, are a significant cause of morbidity and mortality. Wolff-Parkinson-White (WPW) syndrome affects 1 in 500 people and is characterized by accessory atrioventricular pathways in the heart which bypass the normal conduction system and can result in ventricular preexcitation, palpitations and sudden cardiac death. Our laboratory uses novel genetically modified mouse models to study the developmental processes that go awry and produce functional ectopic myocardial tissue.

Education

9/1991 – 5/1995 B.S. Lehigh University (Biochemistry)

8/1997 – 5/2002 Ph.D. Mount Sinai School of Medicine (BiologicalSciences)

8/1995 – 5/2004 M.D. Mount Sinai School of Medicine

6/2004 – 6/2005 Intern in Internal Medicine, Hospital of University of Pennsylvania, Philadelphia, PA

6/2005 – 6/2006 Resident in Internal Medicine, Hospital of University of Pennsylvania, Philadelphia, PA

7/2006 – 6/2011 Fellow, Cardiovascular Disease, Department of Medicine Hospital of University of Pennsylvania, Philadelphia, PA

Academic Positions

7/2011 – 8/2012 Instructor, Department of Medicine University of Pennsylvania, Philadelphia, PA

9/2012 – present  Assistant Professor, Dept. of Medicine and Developmental Biology Washington University School of Medicine

Honors and Awards

Lehigh University

1992 Freshman Chemistry Award

1992 Phi Eta Sigma

1994  Alpha A. Diefenderfer Award in Chemistry

1994  Undergraduate Award in Analytical Chemistry

1994  Alpha Epsilon Delta

1994  Phi Beta Kappa

1995  Ullmann Prize in Chemistry

1995  American Institute of Chemists Foundation Award

1995  Graduation with Highest Honors

Mount Sinai School of Medicine

2000 American Heart Association Councils Travel Award Winner

2001 Graduate School of Biological Sciences Award for Academic Excellence

2003  Graduate School of Biological Sciences Doctoral Dissertation Award

2003 Alpha Omega Alpha Honor Society

2004 Barry Coller Award for Excellence in Clinical Medicine

2004 AMWA’s Glasgow-Rubin Achievement Award

Hospital of the University of Pennsylvania

2004 The William Osler Society of Fellows in Medicine

2009  Department of Medicine Measey Senior Research Fellow

2010 Department of Medicine Bradley Award for Bench Research

2011 Keystone Symposium Travel Award

2011 Keystone Symposium Graduate Student/Postdoc Research Competition Winner

2011  Burroughs Wellcome Foundation Career Award for Medical Scientists

2011  Department of Medicine Bradley Award for Bench Research

2012  Keystone Symposium Travel Award

Washington University in St. Louis

2012 Northwestern Cardiovascular Young Investigators’ Forum Second Place Finalist

Selected publications

• Khandekar A, Springer S, Wang W, Hicks S, Weinheimer CJ, Diaz-Trelles R, Nerbonne JM, Rentschler S. Notch-Mediated Epigenetic Regulation of Voltage-Gated Potassium Currents. Circ Res. 2016 Oct 3.
• Kang C, Qiao Y, Li G, Baechle K, Camelliti P, Rentschler S, Efimov IR. Human Organotypic Cultured Cardiac Slices: New Platform For High Throughput Preclinical Human Trials. Sci Rep. 2016 Jun 30;6:28798.
• Chiplunkar A, Rentschler S. Notch Activation Associated with Poor Outcomes in Heart Failure: Is it Harmful, or not Enough of a Good Thing? J Card Fail. 2016 Mar;22(3):224-5.
• Meyers JD, Jay PY, Rentschler S. Reprogramming the conduction system: Onward toward a biological pacemaker. Trends Cardiovasc Med. 2016 Jan;26(1):14-20.
• Gillers BS, Chiplunkar A, Aly H, Valenta T, Basler K, Christoffels VM, Efimov IR, Boukens BJ, Rentschler S. Canonical wnt signaling regulates atrioventricular junction programming and electrophysiological properties. Circ Res. 2015 Jan 30;116(3):398-406.
• Smith AW, Hoyne JD, Nguyen PK, McCreedy DA, Aly H, Efimov IR, Rentschler S, Elbert DL.  Direct reprogramming of mouse fibroblasts to cardiomyocyte-like cells using Yamanaka factors on engineered poly(ethylene glycol) (PEG) hydrogels.  Biomaterials, 2013; 34(28):6559-71
• Addis RC, Ifkovits JL, Pinto F, Kellam LK, Esteso P, Rentschler S, Christoforou N, Epstein JA, and Gearhart JD.  Optimization of Direct Fibroblast Reprogramming to Cardiomyocytes using Calcium Activity as a Functional Measure of Success.  JMCC, 2013; 60C:97-106.
• Rentschler S, Yen AH, Lu J, Petrenko NB, Lu MM, Manderfield LJ, Patel VV, Fishman GI, Epstein JA. Myocardial Notch signaling reprograms cardiomyocytes to a conduction-like phenotype. Circulation. 2012 Aug 28;126(9):1058-66.
• Rentschler S*, Yen AH, Lu J, Petrenko NB, Lu MM, Manderfield, LJ, Patel VV, Fishman GI, Epstein JA.  Myocardial Notch Signaling Reprograms Cardiomyocytes to a Conduction-Like Phenotype. Circulation, 2012; 126(9):1058-66 PMCID:PMC3607542
• Manderfield L, High F, Engleka K, Liu F, Li L, Rentschler S, Epstein JA.  Notch Activation of Jagged-1 Contributes to the Assembly of the Arterial Wall. Circulation, 2012; 125(2):314-23 PMCID: PMC3260393
• Rentschler S, Harris BS, Kuznekoff L, Jain R, Manderfield L, Lu MM, Morley GE, Patel VV, Epstein JA. Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways. J Clin Invest. 2011 Feb;121(2):525-33.
• Rentschler S, Harris BS, Kuznekoff L, Jain R, Manderfield L, Lu M, Morley GE, Patel VV, Epstein JA.   Notch Signaling Regulates Murine Atrioventricular Conduction and Formation of Accessory Pathways.  JCI, 2011; 121(2):525-33 PMCID: PMC3026731
• Jain R, Engleka KA, Rentschler S, Yuan L, Li L, Epstein JA.  Cardiac Neural Crest Orchestrates Remodeling and Functional Maturation of the Semilunar Valves. JCI, 2011; 121(1):422-30 PMCID: PMC3007154
• Stroud DM, Darrow BJ, Kim SD, Zhang J, Jongbloed MR, Rentschler S, Moskowitz IP, Seidman J, Fishman GI.  Complex genomic rearrangement in CCS-LacZ transgenic mice. Genesis 2007; 45(2):76-82

• Rentschler S, Zander J, Burns K, France D, Levine R, Porter G, Rivkees SA, Morley GE, Fishman GI.  Neuregulin-1 promotes formation of the murine cardiac conduction system.  PNAS 2002; 99:10464-9 PMCID: PMC124940
• Degenhardt K, Rentschler S, Fishman G, Sassoon DA.  Cellular and cis-regulation of EN-2 expression in the mandibular arch.  Mech. Dev. 2002; 111:125-36

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