- Affinity Groups:
Genes,Genomics and Pediatric Disease
CVI Program Unit(s):
Cardiovascular Development / Congenital Heart Disease
CVI Research Description:
Regulation of cardiac morphogenesis and function
Key Words: Cardiac development, morphogenesis, compaction, epigenetics, microgenomics, congenital heart disease
The Gruber Lab has three general areas of interest. First, we are interested in the molecules that control differentiation and maturation of ventricular myocytes (after specification). Specialization of ventricular myocytes from compact zone myocytes into trabecular myocytes provides a native system to study the maturation of muscle cells. This is important because 1) morphogenic processes that contribute to some CHD phenotypes are likely dependant upon altered maturation of ventricular myocytes (Shone?s, non-compaction, Type III and IV VSD, and others; and 2) it provides a native system to study the progressive loss of myocyte proliferative capacity from a compact to a trabecular myocytes. We are taking a microgenomic approach to identify novel pathways that control differentiation and maturation of ventricular myocytes. Using the vast clinical resources at CHOP, we have the ability to correlate animal models of congenital heart disease with human disease.
Second, we are interested in uncovering the contribution of epigenetic programs to cardiac development and response to injury. Using a combination of chemical inhibitors and gene-targeted mice, we use a variety of injury and analysis techniques including murine ischemia-reperfusion injury, invasive hemodynamic monitoring, echocardiographic imaging, and, in collaboration with Vic Patel, electrophysiologic techniques to identify signaling pathways that regulate these events.
Third, we are interested in the provenance of cardiac chimerism and the potential contributions of either extracardiac or tissue-derived cardiac progenitor cells in cardiac development and disease. Using murine heterotopic heart transplantation in mice, we use a variety of genetic and imaging techniques to identify signaling pathways that may allow these rare events. We are also working towards the isolation, purification, and complete characterization of human Isl1+ progenitor cells with an eye towards the production of CHD disease-specific cell lines.
Lab Contact Information:
905 BRB II/III?
421 Curie Boulevard
Philadelphia, PA 19104
website: Gruber Lab
- Assistant Professor of Surgery at University of Pennsylvania School of Medicine (2002 – 2008)
- Assistant Professor of Surgery at the Children's Hospital of Philadelphia (2008 – 2011)
- M.D., NIH Medical Scientist Training Program, University of Pennsylvania School of Medicine (1992)
- Ph.D., University of Pennsylvania, Department of Biochemistry and Biophysics (1992)
- B.A., Biochemistry, University of Pennsylvania (1985)
- Shake JG, Martin BJ, Gruber PJ, Senechal G, Pittenber, MF, Redmond JM, and Baumgartner WA.. In-vivo mesenchymal stem cell grafting in a swine myocardial infarct model: Molecular and physiological consequences.. Ann Thorac Surg. Vol 73(6). 2002:1919-1925.
- Gruber PJ, Askin FB, and Heitmiller RF.. Pulmonary artery aneurysm in a pregnant woman.. Annals of Thoracic Surgery. Vol 71(3) . 2001 Mar:1023-1025.
- Lacour-Gayet F, Piot D, Zoghbi J, Serraf A, Gruber PJ, Mace L, Touchot A, Planche C. Surgical management and indication of left ventricular retraining in arterial switch for transposition of the great arteries with intact ventricular septum.. European Journal of Cardio-Thoracic Surgery. Vol 20(4) . 2001 Oct:824-829.
- Gruber PJ, Sprecher BS, Doty JR, Salazar JD, Nyhan D, Conte JV, Baumgartner WA, Misek DE, Puravs E, Krause M, Hanash S, Balser JR, and Gruber SB.. Comprehensive proteomic and genomic expression analysis of cardiopulmonary bypass.. Cardiology in the Young. Vol 11(Suppl. 1) . 2001:194.
- Christiansen G, Minamisawa S, Gruber PJ, Wang Y, and Chien KR.. High-efficiency, long-term cardiac expression of foreign genes in living mouse embryos and neonates.. Circulation. Vol 101(2) . 2000 Jan 18:178-184.
- Heitmiller RF, Gruber PJ, Swier P, and Singh N.. Long-segment substernal jejunal esophageal replacement with internal mammary vascular augmentation.. Diseases of the Esophagus. Vol 13. 2000:240-242.
- Christensen G and Gruber PJ.. Embryonic and neonatal cardiac gene transfer: Protocols and applications.. Methods in Molecular Medicine: Cardiac Gene Transfer. New York: Academic Press; 2000:169-178.
- Toma C, Byrne BJ, Golob J, Gruber PJ, Murry CE, Pittenger MF, and Kessler PD.. Efficient myogenic conversion of human mesenchymal stem cells with forced expression of MyoD.. Circulation. Vol 100(SuppI). 1999:I-164.
- Gruber PJ, Walinsky PL, Peck EA, Zhang S, Kambouris NG, Tomaselli GF, Nyhan D, Baumgartner WA, and Balser JR.. Altered ion channel expression following cardiopulmonary bypass.. Circulation. Vol 100(SuppI). 1999:I-270.
- Gruber PJ, Kubalak SW, and Chien KR.. Down-regulation of atrial markers during cardiac chamber morphogenesis is irreversible in murine embryos.. Development. Vol 125(22) . 1998 Nov:4427-4438.