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Cardiovascular Medicine

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Research Offices

Falk Cardiovascular
Research Center
300 Pasteur Drive
Stanford, CA 94305
T: (650) 723-6141
F: (650) 725-1599

Cardiovascular Clinic

Boswell Building
300 Pasteur Drive
Stanford, CA 94305
Hours: 8:30 AM - 5 PM Mon-Fri
T: (650) 723-6459
F: (650) 723-8392

School-wide Information


	Research Overview

Ching-Pin Chang, MD, PhD

Residency in Internal Medicine, Massachusetts General Hospital, Harvard University
Cardiology Fellowship, Stanford University Medical Center
Assistant Professor of Medicine, Stanford University

Laboratory Research

My laboratory focuses on the mechanisms of cardiovascular development, particularly how the three major types of cardiac cells (endocardial, myocardial and epicardial cells) and neural crest cells interact with each other to generate heart tissues. We are interested in the transcriptional and signaling events that coordinate their interactions and assembly into heart tissues. The long-term goal is to understand the developmental mechanisms that control tissue formation and recapitulate the developmental processes for therapeutic or regenerative purposes. Furthermore, we have generated mouse models of cardiomyopathy and models that allow us to study the repair mechanisms of vascular injury in adult. We aim to applying lessons learned from our developmental studies to investigating the mechanisms of adult disease. Current projects are summarized below.

Heart Valve Morphogenesis

Using pharmacological inhibitors, tissue-specific gene disruption and conventional gene knockout in mice, we have demonstrated that calcineurin/NFAT signaling plays two sequential and critical roles in the initiation and propagation of heart valve morphogenesis. The initiation of valve formation requires myocardial NFAT to repress the expression of VEGF (vascular endothelial growth factor). We are studying how VEGF interacts with NFAT signaling during valve formation, and the molecular mechanism of NFAT-mediated VEGF repression.

Myocardial Development and Coronary Angiogenesis

Using tissue-specific gene knockout technology in mice, we have generated mouse lines deficient in endocardial transcription factors or chromatin remodeling molecules. One of the mutant lines develops abnormal myocardial growth and trabeculation. These observations suggest that endocardial factors are required for myocardial development. We are studying the molecular and cellular mechanisms of how endocardial cells control myocardial development. Furthermore, we have generated several mouse lines lacking myocardial or epicardial transcription factors or chromatin remodeling molecules. These mice fail to form mature myocardium, interventricular septum or coronary arteries. We are investigating the molecular basis of these cardiac and vascular defects.

Patterning of Cardiac Outflow Tract and Great Arteries

Using compound gene mutations in mice, we have demonstrated that Pbx gene family members (homeodomain proto-oncogenes) are essential for the patterning of cardiac outflow tracts and great arteries. We are investigating the molecular pathways controlled by Pbx genes during cardiac development.

Cardiomyopathy and Vascular injury

We have generated a mouse model of restrictive cardiomyopathy and a mouse model that allows us to study the signaling events during the repair process following vascular injury such as balloon angioplasty. These models are directly relevant to a specific type of human congestive heart failure and the restenosis following angioplasty and stenting seen in clinical cardiology. We are investigating the pathogenesis of cardiomyopathy and the mechanisms of vascular restenosis following injury.

Ching-Pin Chang

Heart Valve Morphogenesis

Myocardial Trabeculation

Great Artery Angiography

Cardiac Pressure Tracing

Lab Members

Postdoctoral Fellows

Kryn Stankunas

Ph.D. in Developmental Biology, Stanford University
Postdoctoral Fellow of American Heart Association

Ching Shang

Ph.D. in Molecular and Cell Biology, UC Berkeley
Postdoctoral Fellow of Kirschstein-NRSA Individual Fellowship

Miriam Zeini

Ph.D. in Biochemistry and Molecular biology, Universidad Complutense Madrid, SPAIN
Postdoctoral Fellow of Marie Curie Fellowship, European Commission

Joshua E. Lehrer-Graiwer

M.D., UCSF School of Medicine
M. Phil., Biological Science, Cambridge University, England
Cardiology Fellow of Vascular Medicine Fellowship

Karen Twu

Ph.D. in Microbiology, University of Texas at Austin
McCormick Fellowship
Postdoctoral Fellow of Kirschstein-NRSA Individual Fellowship

Graduate Students

Calvin Hang

B.A., Molecular and Cellular Biology, UC Berkeley
Predoctoral Student, Cancer Biology Program, Stanford University

Students

Tiffany Dao

Undergraduate, Biochemistry, Stanford University
VPUE Grant for Undergraduate Research

Geoffrey Krampitz
Geoffeory Krampitz
Bioengineering, Johns Hopkins University
Medical Student, Stanford University
Howard Hughes Medical Fellowship
The Paul & Daisy Soros Fellowship for New Americans

Gene Ma

Biological Sciences, Stanford University
Medical Student, Stanford University
Howard Hughes Medical Fellowship

Zhi-Yang Tsun
Zhi-Yang Tsun.JPG
Undergraduate, Bioengineering, UCSD
Undergraduate Research Fellow of American Heart Association

Katherine Zhang

Undergraduate, Bioengineering and Material Science, UC Berkeley
Undergraduate Research Fellow of American Heart Association

Selected Publications

Stankunas K, Hang CT, Tsun ZY, Chen H, Lee NV, Wu JI, Shang C, Bayle JH, Shou W, Iruela-Arispe ML, Chang CP. Endocardial Brg1 Represses ADAMTS1 to Maintain the Microenvironment for Myocardial Morphogenesis. Dev Cell. 2008 Feb; 14(2): 298-311. PMID: 18267097 [PubMed - in process] (PDF)
Wu H, Kao SC, Barrientos T, Baldwin SH, Olson EN, Crabtree GR, Zhou B, Chang CP "Down syndrome critical region-1 is a transcriptional target of nuclear factor of activated T cells-c1 within the endocardium during heart development." J Biol Chem 2007; 282: 42: 30673-9 (PDF)
Jia Q, McDill BW, Li SZ, Deng C, Chang CP, Chen F "Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effects." Dev Biol 2007; 311: 1: 172-84 (PDF)
Sheikh AY, Lin SA, Cao F, Cao Y, van der Bogt KE, Chu P, Chang CP, Contag CH, Robbins RC, Wu JC "Molecular imaging of bone marrow mononuclear cell homing and engraftment in ischemic myocardium." Stem Cells 2007; 25: 10: 2677-84 (PDF)
Chang CP, Neilson JR, Bayle JH, Gestwicki JE, Kuo A, Graef IA, Crabtree GR. A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis. Cell 2004 Sept; 118, 649-663. Editorial commentary: Lambrechts D, Carmeliet P. Sculpting heart valves with NFAT and VEGF. Cell 2004 Sept; 118, 532-534 (PDF) (Cover Headline)
Arron J, Winslow M, Polleri A, Chang CP, Wu H, Gao X, Neilson J, Chen L, Heit J, Kim S, Yamasaki N, Miyakawa T, Francke U, Graef I, Crabtree G. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature. 2006 Jun 1;441(7093):595-600 (PDF)
Chang CP, Shen WF, Rozenfeld S, Lawrence HJ, Largman C, Cleary ML. Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. Genes and Development, 1995 March 15, 9(6):663-74 (PDF)
Kofidis T, de Bruin JL, Hoyt G, Lebl DR, Tanaka M, Yamane T, Chang CP, Robbins RC. Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle. J Thorac Cardiovasc Surg. 2004 Oct; 128(4), 571-8 (PDF)
Kofidis T, de Bruin JL, Hoyt G, Ho Y, Tanaka M, Yamane T, Lebl DR, Swijnenburg RJ, Chang CP, Quertermous T, Robbins RC "Myocardial restoration with embryonic stem cell bioartificial tissue transplantation." J Heart Lung Transplant 2005; 24: 6: 737-44. (PDF)
Chang CP, McDill BW, Neilson JR, Joist HE, Epstein JA, Crabtree GR, Chen F. Calcineurin is required in the urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery. J Clin Invest 2004 Apr;113(7):1051-8. Editorial commentary: Mendelsohn C. Functional obstruction: the renal pelvis rules. J Clin Invest 2004 Apr;113(7): 957-959 (PDF)
Chang CP, Chen L, Crabtree GR. Sonographic staging of the developmental status of mouse embryos in utero. Genesis: the Journal of Genetics and Development 2003;36(1):7-11 (PDF)
Rugolotto M, Chang CP, Hu BS, Schnittger I, Liang D. Clinical use of cardiac ultrasound performed with a hand-carried device in patients admitted for acute cardiac care. Am J Cardiol 2002; 90(9):1040-1042
Pelletier M, Chang CP, Vagelos R and Robbins R. Alternative approach for use of a left ventricular assist device with a thrombosed prosthetic valve. Journal of Heart and Lung Transplantation, 2002; 21(3):402-404
Derek P, Batchelor A, Chang CP, Cleary ML, and Wolberger, C. Crystal structure of a HoxB1-Pbx1a heterodimer bound to DNA: Role of the hexapeptide and a fourth homeodomain helix in complex formation." Cell, Vol. 96, 587-597, Feb. 1999 (PDF)
Chang CP, Jacobs Y, Nakamura T, Jenkins NA, Copeland NG, Cleary ML. Meis proteins are major in vivo DNA binding partners for wild-type but not chimeric Pbx proteins. Molecular and Cellular Biology, Oct. 1997, Vol. 17, No. 10, 5679-5687. (PDF)
Chang CP, De Vivo I, Cleary ML. The Hox cooperativity motif of chimeric oncoprotein E2a-Pbx1 is necessary and sufficient for oncogenesis. Molecular and Cellular Biology, Jan.1997, Vol.17, No. 1, 81-88. (PDF)
Chang CP, Luciano Brocchieri, Shen WF, Largman C, Cleary ML. Pbx modulation of Hox homeodomain N- terminal arms establishes a gradient of DNA-binding specificities across the Hox locus. Molecular and Cellular Biology, April 1996, Vol. 16, No 4, 1734-1745 (PDF)