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.
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
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
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
- 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