Assistant Professor of Medicine
Director, Ross Flow Cytometry Core Facility

Departmental Address:
Ross Reserach Building
Room 1029
720 Rutland Avenue
Baltimore, MD  21205

Administrative Office:
410-614-0041
zwang51@jhmi.edu



 

Dr. Wang is a research faculty and will not see patients directly.

Clinical/Academic Interests

Hematopoiesis and cardiovascular differentiation from stem cells, and regenerative medicine.

Research Interests 

The long-term research goal of the Wang laboratory is to understand the molecular mechanisms that regulate cardiovascular and hematopoietic differentiation of pluripotent stem cells (PSCs), including embryonic stem (ES) cells and induced-pluripotent stem (iPS) cells. Pluripotent stem cells hold great potential for regenerative medicine, and gene therapy. Defining the molecular links between differentiation outcomes will provide important information for designing rational methods of stem cell manipulation.  Current projects including: 

Hematopoietic development of pluripotent stem cells 
CD34 hematopoietic progenitor cells (HPC) obtained from bone marrow and cord blood are used for bone marrow transplantation to treat blood diseases, such as leukemia. We and other have demonstrated that hESC-derived CD34+ cells contain hematopoietic progenitor cells. Our goal is to establish a serum-free system to efficiently generate CD34+ hematopoietic stem/progenitor cells, erythrocytes, and platelets from pluripotent stem cells.

Molecular regulation of vascular differentiation from human ES and iPS cells
Cardiovascular disease is the leading cause of mortality in the US, and poses an increasing health problem worldwide. Stem cell therapies hold considerable promise for the treatment of ischemia in patients with one or more of the following disorders: diabetes, obesity, hypertension, or old age. Our goal is to identify signals and factors to reliably direct pluripotent stem cell differentiation to vascular progenitors capable of generating two essential components of blood vessels: endothelial cells and smooth muscle cells, and to provide a superior cell type for vascular regeneration in the ischemic tissues of patients with peripheral vascular diseases (PVD).

EphB4-ephrinB2 signaling in stem cell differentiation
Pluripotent stem cells, such as ES cells and iPS cells, have not only emerged as a promising source of cells for cardiac transplantation, but also provide a unique system to study cardiomyocyte generation. Cell-surface molecule, ephrinB2, is the ligand for the tyrosine kinase receptors EphB4. Interaction between ephrinB2- and EphB4-expressing cells results in bidirectional signal transduction. The goal of this project is to decipher the functional role of EphB4-ephrinB2 signaling during stem cell differentiation. We will determine the role of EphB4-ephrinB2 signal in hematopoietic and cardiovascular development.  

Dr. Wang also directs the Ross Flow Cytometry Core Facility at the Department of Medicine.

Education/Training

• BS, Biochemical Engineering, East China University of Science and Technology
• Ph.D., Biochemistry, Boston University School of Medicine (Katya Ravid’s laboratory)
• Postdoctoral Research, the Center of Regenerative Medicine at Massachusetts General Hospital and Harvard University Stem Cell Institute (David Scadden’s laboratory)

Selected Publications

1. Wang Z, Zhang Y, Kamen D, Lees E, Ravid K.  Cyclin D3 is essential for megakaryocytopoiesis.  Blood. 1995, 86:3783-8.
2. Zhang Y, Wang Z, Ravid K.  The cell cycle in polyploid megakaryocytes is associated with reduced activity of cyclin B1-dependent cdc2 kinase.  J Biol Chem. 1996, 27:4266-72.
3. Wang Z, Sicinski P, Weinberg RA, Zhang Y, Ravid K.  Characterization of the mouse cyclin D3 gene: exon/intron organization and promoter activity.  Genomics. 1996, 35:156-63.
4. Zhang Y, Wang Z, Liu DX, Pagano M, Ravid K.  Ubiquitin-dependent degradation of cyclin B is accelerated in polyploid megakaryocytes.  J Biol Chem. 1998, 273:1387-92.
5. Wang Z, Zhang Y, Lu J, Sun S, and Ravid K.  Mpl ligand enhances the transcription of the cyclin D3 gene: a potential role for Sp1 transcription factor.  Blood. 1999, 93:4208-21.
6. Zhang Y, Sun S, Wang Z, Thompson A, Kaluzhny Y, Zimmet J, Ravid K.  Signaling by the Mpl receptor involves IKK and NF-kappaB. J Cell Biochem. 2002, 85:523-35.
7. Poznansky MC, Olszak IT, Evans RH, Wang Z, Foxall RB, Olson DP, Weibrecht K, Luster AD, Scadden DT.  Thymocyte emigration is mediated by active movement away from stroma- derived factors. J Clin Invest. 2002, 109:1101-10.
8. Wang Z, Miura N, Bonelli A, Mole P, Carlesso N, Olson DP, Scadden DT.  Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. Blood.  2002, 99:2740-7.
9. Wang Z, Shao Y., Cohen K., Mole P., Dombkowski D. and Scadden DT. Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels. Blood. 2004, 103:100-9.
10. Li ZJ, Wang Z, Zheng YZ, Xu B, Yang RC, Scadden DT and Han HC.  Kinetic Expression of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) during Embryonic Stem Cell differentiation. J Cell Biochem. 2005, 95:559-70.
11. Chen T, Bai H, Shao Y, Arzigian M, Janzen V, Attar E, Xie Y, Scadden DT and Wang ZZ.  Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro. Stem Cells. 2007; 25:392-401.
12. Wang ZZ^#, Au P, Chen T, Shao Y, Daheron LM, Bai H, Arzigian M, Fukumura D, Jain RK^# and Scadden DT^#.  Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nat Biotechnol. 2007; 25:317-8. (^#co-corresponding authors)
13. Shao L, Feng W, Sun Y, Bai H, Liu J, Currie C, Kim J, Gama R, Wang Z, Qian Z, Liaw L, and Wu WS.  Generation of iPS cells using defined factors linked via the self-cleaving 2A sequences in a single open reading frame. Cell Res.  2009; 19:296-306.
14. Bai H, Gao Y, Arzigian M, Wojchowski DM, Wu WS, Wang ZZ.  BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway. J Cell Biochem. 2010; 109(2):363-74.
15. Sun Y, Shao L, Bai H, Wang ZZ, and Wu WS.  Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration. Blood. 2010; 115(9):1709-17.
16. Kuang SQ, Bai H, Fang ZH, Lopez G, Yang H, Tong WG, Wang ZZ, and Garcia-Manero G.  Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia. Blood. 2010; 115(12):2412-9.
17. Shao L, Sun Y, Zhang Z, Feng W, Gao Y, Cai Z, Wang ZZ, Look AT, and Wu WS.  Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation. Blood. 2010; 115(23):4707-14.
18. Jiang H, Lin X, Feng Y, Xie Y, Han J, Zhang Y, Wang ZZ, Chen T. Hemato-endothelial differentiation from lentiviral-transduced human embryonic stem cells retains durable reporter gene expression under the control of ubiquitin promoter. Cytotechnology. 2010; 62(1):31-42.
19. Chen K, Bai H, Arzigian M, Gao YX, Bao J, Wu WS, Wu L, Wang ZZ.  Endothelial cells regulate cardiomyocyte development from embryonic stem cells. J Cell Biochem. 2010; 111(1):29-39.
20. Zhang Z, Gao YX, Gordon A, Wang ZZ, Qian Z, Wu WS.  Efficient generation of fully reprogrammed human iPS cells via polycistronic retroviral vector and a new cocktail of chemical compounds. PLoS One. 2011; 6(10):e26592.
21. Bai H, Chen K, Gao YX, Arzigian M, Xie YL, Malcosky C, Yang YG, Wu WS, Wang ZZ. Bcl-xL enhances single-cell survival and expansion of human embryonic stem cells without affecting self-renewal. Stem Cell Res. 2012; 8(1):26-37.
22. Tang Y, Bai H, Urs S, Wang Z, Liaw L. Notch1 activation in embryonic VE-cadherin populations selectively blocks hematopoietic stem cell generation and fetal liver hematopoiesis. Transgenic Res. 2012 Aug 1. [Epub ahead of print]