Kenneth R. Chien, MD, PhD
Director, MGH Cardiovascular Research Center
Department of Cell Biology, HMS
Harvard Stem Cell Institute
Massachusetts General Hospital
Richard B. Simches Research Center, CPZN 3208
185 Cambridge St.
Boston, MA 02114
Tel: (617) 643-3440
Fax: (617) 643-3451
Web Page: MGH Cardiovascular Research Center
The Chien lab focuses on the development of stem cell models of heart development and disease, based on the recent identification of novel mouse and human cardiac progenitor cells (Nature, 2005). Recently, in murine ES cells, they have discovered a single, master cardiovascular stem cell that can generate diverse endothelial/smooth muscle/cardiac lineages, a study which is now being extended into human ES cells. The type of current projects include:
Identifying specific cell markers
The first step in assessing the regenerative capacity of cardiac progenitor cells is to identify and unravel the nature of these cells. Focusing on recently identified cell groups, researchers are isolating the signals and steps in the development of a progenitor cell into a mature heart muscle cell. This process involves the use of tools and techniques such as transcriptional (signal) profiling and antibody generation. In addition, investigators are using colored tags to track the migration, incorporation, and function of these cells within the cardiovascular system.
Building a genealogy tree
In order to design effective cell replacement treatments, researchers must first learn how a normal cardiac progenitor cell develops into a mature heart muscle cell. Creating a genealogy tree (called a lineage map) will provide investigators with the pathways particular cells can take and indicate where they may degenerate. RNAi, chemical screening, and microarray analysis are some of the technologies used.
Developing disease-specific human ES cell lines
By using genetic engineering of human ES cell lines carrying specific genes responsible for heart disease, HSCI researchers will provide models with which to study certain properties of these cells. They will be able to study the phenomena of homing, asking whether stem cells migrate to the correct location (niche) within the body; of engraftment, seeking to learn if these cells establish themselves within that niche; of maturation, following the development of progenitor cells to maturity; and finally, of function, to learn if these mature cells behave like cardiac and vascular cells.
- Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages.
Nature. 2005 Feb 10;433(7026):647-53.
- Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, ChenY, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz K-L, Chien KR. Multipotent embryonic Isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 2006 Dec 15; 127(6):1151-1165.
- Qyang Y, Martin-Puig S, Chiravuri M, Chen S, Granger A, Bu L, Jiang X, Moretti A, Caron L, Clarke J, Laugwitz K-L, Moon RT, Gruber P, Ding S, Chien, KR. The In Vivo Renewal and Differentiation of Isl1+ Cardiovascular Progenitors is Controlled by a Wnt/b-Catenin Pathway. Cell Stem Cell 2007 August; 1: 165-179.
- Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao, Y, Roberts DR, Huang PL Domian IJ, Chien KR. Human ISL1 Primordial Heart Progenitors Generate Diverse Multipotent Cardiovascular Cell Lineages. Nature 2009, In Press.
BBS webpage updated 12/02/2009