The long-term goal of our laboratory is to gain a comprehensive understanding of the molecular mechanisms that govern the adult stem cell fate determination, and to apply the knowledge obtained from these studies to the development of new stem cell transplantation strategies and gene therapies for treating cancer and other diseases. Our study is focused on hematopoietic stem cells (HSCs).
HSCs are defined by their ability to self-renew and to differentiate into all blood cell types. These very rare cells form the basis of bone marrow transplantation for treatment of leukemia and other cancers, and are also a promising cell target for developing gene therapies for treating a broad variety of human diseases. However, development of these important clinical applications of HSCs is severely hampered by the lack of understanding of the extracellular and intracellular signals that govern their fates and the difficulty in ex vivo expansion of these cells.
Recently we identified several groups of novel growth factors for HSCs, including Angiopoietin-like proteins (Angptls). We subsequently developed a very potent but simple serum-free culture system, which is capable of stimulating a 24-30 fold expansion of long-term HSCs. This provides a great system to study the control of cell fates of HSCs: self-renewal, differentiation, apoptosis, and mobilization, and may provide us the opportunity to uncover the mystery of "stemness" of adult stem cells. We therefore seek to study:
1. mechanisms by which Angiopoietin-like proteins regulate HSC expansion, and the interaction of HSCs and their in vivo microenvironment.
2. ex vivo expansion of HSCs for cell therapy and gene therapy.
3. the interplay between HSCs and cancer.
RESEARCH INTERESTS
Hematopioietic stem cells and microenvironment
Ex vivo expansion of HSCs for cell therapy and gene therapy
Interplay between stem cells and cancer
Mammary gland epithelial stem cells
RECENT PUBLICATIONS
Zhang CC, Kaba M, Ge G, Xie K, Tong W, Hug C, Lodish HF, "Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells." Nat Med, 12(2):240-5, February 2006
Zhang CC, Steele AD, Lindquist S, Lodish HF, "Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal." Proc Natl Acad Sci U S A, 103(7):2184-9, February 2006
Liao MJ*, Zhang CC*, Zhou B*, Zimonjic DB, Mani SA, Kaba M, Gifford A, Reinhardt F, Popescu NC, Guo W, Eaton EG, Lodish HF, Weinberg RA. (* co-first author), "Enrichment of a population of mammary gland cells that forms mammospheres and has in vivo repopulating activity" Cancer Research, 67 September 2007
Zhang CC, Kaba M, Iizuks S, Huynh H, Lodish HF, "Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells" Blood, 11:3415-3423, April 2008
Huynh H, Iizuka S, Kaba M, Kirak O, Zheng J, Lodish HF, Zhang CC, "IGFBP2 secreted by a tumorigenic cell line supports ex vivo expansion of mouse hematopoietic stem cells" Stem Cells, March 2008
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