Research

Our research focuses upon the molecular basis of cardiac development and physiology, presently investigating three areas. First, we are focusing on the molecular mechanisms that regulate cardiac morphogenesis. We are characterizing global mechanisms that regulate ventricular identity and maturation during mid-gestation using laser capture mirodissection (LCM) and microgenomic approaches. Second, we have identified human, tissue-derived cardiac progenitor cells and are rigorously characterizing their physiology and developmental potential. From these experiments we hope to gain a deeper understanding of regenerative abilities of the heart and the potential for creating in vitro disease models. Third, we have fostered a collaborative, international consortium of centers of congenital heart disease. Using genomic-based approaches informed by insights from developmental biology, we are identifying novel loci that contribute to the development of congenital heart disease. These approaches lead to the generation of candidate genes whose mechanism is subsequently studied through gene targeting studies in the mouse.

 

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Publications

Representative Publications:

Anne Granger, Ibrahim Abdullah, Faith Huebner, Andrea Stout, Tao Wang,Thomas Huebner, Jonathan A. Epstein, and Peter J. Gruber. Histone deacetylase inhibition reduces myocardial ischemia-reperfusion injury in mice. The FASEB Journal. 22, 3549–3560 (2008).

Piel DA, Gruber PJ, Weinheimer CJ, Courtois MR, Robertson CM, Coopersmith CM, Deutschman CS, and Levy RJ. Mitochondrial resuscitation with exogenous cytochrome c in the septic heart. Crit Care Med. 35(9):1-9 (2007).

Qyang Y, Martin-Puig S, Chiravuri M, Chen S, Xu H, Bu L, Jiang X, Lizhu Lin, Granger A, Moretti A, Caron L, Wu X, Clarke J, Taketo MM, Laugwitz K-L, Moon RT, Gruber PJ, Evans SM, Ding S, and Chien KR. The Renewal and Differentiation of Isl1+ Cardiovascular Progenitors Are Controlled by a Wnt/β-Catenin Pathway. Cell Stem Cell. 1:1-15 (2007).

Trivedi CM, Luo Y, Yin Z, Zhang M, Zhu W, Wang T, Floss T, Goettlicher M, Noppinger PR, Wurst W, Ferrari VA, Abrams CS, Gruber PJ and Epstein JA. HDAC2 regulates the cardiac hypertrophic response by modulating Gsk3beta activity. Nature Medicine. 13(3):324-331 (2007).

Gruber PJ, Fuller S, Cleaver KM, Abdullah I, Gruber, SB, Nicolson SC, Gaynor JW, Wernovsky G, and Spray TL. Early results of single-stage biventricular repair of severe aortic hypoplasia or atresia with ventricular septal defect and a normal left ventricle. Journal of Thoracic and Cardiovascular Surgery. 132(2):260-263, (2006).

Laugwitz KL, Moretti A, Lam J, Gruber PJ, Chen Y, Woodward S, Lin L-Z, Cai C-L, Lu MM, Reth M, Platoshyn O, Yuan JX-J, Evans SA and Chien KR. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature. 433(7026):647-653 (2005).

Gruber PJ. Cardiac Developments: New concepts. Clinics in Perinatology. 32(4):845-855 (2005).

Abdullah I, Lepore JJ, Epstein JA, Parmacek MA and Gruber PJ. MRL mice fail to heal the heart is response to ischemia-reperfusion injury. Wound Repair and Regeneration. 13:205-208 (2005).

Gruber PJ, and Epstein JA. Development gone awry: Congenital Heart Disease. Circulation Research. 94(3): 273-283 (2004).

Kook H, Lepore J, Gruber PJ, Lu MM, Mackay J, Zhou R, Ferrari V. and Epstein J. Cardiac hypertrophy and histone deacetylase-dependant transcriptional repression mediated by the homeodomain protein HOP. Journal of Clinical Investigation.112(6): 863-871 (2003).

Gitler AD, Lepore J, Epstein JA, and Gruber PJ. Molecular markers of cardiac endocardial cushion development. Developmental Dynamics. 228(4): 643-650 (2003).

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 73(6):1919-1925 (2002).

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 101(2):178-184 (2000).

Gruber PJ, Kubalak SW and Chien KR. Down-regulation of atrial markers during cardiac chamber morphogenesis is irreversible in murine embryos. Development 125(22):4427-4438 (1998).

Ruiz-Lozano P, Doevendans P, Brown A, Gruber PJ, and Chien KR. Developmental expression of the murine spliceosome-associated protein mSAP49. Developmental Dynamics 208(4):482-490 (1997).

Gruber PJ, Kubalak SW, Pexieder T, Sukov HM, Evans RM, and Chien, KR. RXRα deficiency confers genetic susceptibility for aortic sac, conotruncal, atrioventricular cushion, and ventricular muscle defects in mice. Journal of Clinical Investigation. 98(6):1332-1343 (1996).

Grace AA and Gruber PJ. Understanding cardiac development. Lancet 345(8954):915-916 (1995).

 

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Protocols

Content under revision.

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Databases / Links

Mouse Genome Informatics

eGenome

Pubmed

GeneCards

OligoCalc

DNA motif comparison (STAMP)

BioDBx

eJournals

ISI Web of Science

Google Scholar

Ensemble

Genome Browser

NCBI

Swiss-Prot

zFIN

Interactome- BOND

Human Protein Reference Database - Interactome

Chi-Squared / P-value Calculator

PAINT: Promoter Analysis and Interaction Network Toolset (V 3.5)

NIH

NIH

NIH eRA Commons

CRISP

Lab

Computer (SOMIS)

Penn Bioinformatics Core

Penn Computer Connection

IACUC (CHOP)

IACUC (Penn)

IDT oligo order

Histology Core

Lab Safety (Penn)

Microsurgery Core

Morpholino order

Penn Microarray Core Facility

TaqMan order

ULAR

U@Penn

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Contact

Peter J. Gruber, M.D., Ph.D.
Assistant Professor
Children's Hospital of Philadelphia
12NW23, Main
34th and Civic Center Blvd.
Philadelphia, PA 19104

Email: pgruber@mail.med.upenn.edu
Hospital Office: 215.590.2710
Lab Office: 215.573.4816
Lab: 215.573.7215
Fax: 215.590.2715

Administrative assistant : Christine Seavey
Office: 215.590.2710
Email: seavey@email.chop.edu

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Developmental Biology Lab Members

Ryan Cobb, 215-573-2598, ryacobb@gmail.com

Denise Juhr, 215-573-7215, d.juhr@web.de

 

Students:

Amanda King

Amanda Klinger

Clinical Coordinators

Nancy Burnham, 215.590.5806, burnhamn@email.chop.edu

Diane Hartman, 215.590.5806, hartman@email.chop.edu

Jennifer Hufford, 215.590.5806, hufford@email.chop.edu

Jennifer Raue, 215.590.5806, raue@email.chop.edu

 

Collaborators

Kenneth Chien (MGH/Harvard): Isl1 progenitor cells

Pieter Doevendans (UMC Utrecht): cardiac progenitor cells

Jonathan Epstein (U. Penn): HDACs in development

Stephen Gruber (U. Michigan): .BRCA in development; cancer and CHD; cardiac genomics

Wayne Hancock (CHOP): HATs in transplant tolerance

Richard Shultz (U. Penn): HATs in development

Amy Wagers (Joslin Diabetes Center/Harvard): skeletal muscle progenitor cells

 

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Alumni

Ibrahim Abdullah, M.D.

Danna Doraotaj, M.D.

Anne Granger, Ph.D.

Faith Huebner, B.S.

Thomas Huebner, B.S.

Yan Li, Ph.D.

Arun Padmanabhan

Anbiao Wang, M.D.

Diane Worrad, Ph.D.

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Positions Available

June 5, 2009
Post-doctoral position immediately available.
We are looking for a motivated, post-doctoral fellow to study the molecular basis of second heart field defects using in vitro human models. Experience in human ES and iPS cell culture and basic molecular biological techniques is preferred. Please contact Peter for further information.