Research Specialist

EDUCATION AND POSITIONS HELD:

• B.Sc., Department of Biology, Chinese University of Hong Kong (1978)
• M.Phil., Department of Anatomy, University of Hong Kong (1982)
• Ph.D., Department of Medical Biology, University of Melbourne (1986)
• Postdoctoral Fellow, Molecular Biology and Virology Laboratory, The Salk Institute, San Diego, USA (1986-1989)
• Research Officer, Cancer Research Unit, The Walter and Eliza Hall , Institute of Medical Research, Melbourne, Australia (1989-1993)
• Senior Research Officer, Queensland Institute of Medical Research/ Conjunct Lecturer, Department of Pathology, University of Queensland; Brisbane, Australia (1993-2002)
• Visiting Professor, Graduate Institute of Cellular and Molecular Biology, Taipei Medical University
• Professor, Institute of Bioscience and Bio-technology, National Taiwan Ocean University

HONORS:

• American Cancer Society Junior Post-Doctoral Fellowship (1986-1988)
• The Croucher Foundation Post-Graduate Scholarship (1982-1985)
• Ad hoc reviewer for Blood, Experimental Hematology & Journal of Experimental Biology

RESEARCH INTERESTS:

Hematopoietic Stem Cells: Self Renewal mechanism(s) and Genetic Manipulation

Research in the Experimental Hematology Laboratory is primarily evolved around the primitive haematopoietic stem cells (PHSC). We are currently focused on elucidating mechanism(s) governing the self-renewal and commitment/differentiation decision when PHSC undergo cell divisions. Figure 1 summarizes a current model of major signalling pathways in the maintenance of pluripotency of embryonic stem cells (ES) and our working model on potential signalling pathways operating in PHSC.

In the laboratory we routinely employ the fluorescence-activated cell sorting technique to purify the RhloHolo/spLin-Kit+Sca1+ mouse PHSC and use these cells to study the effect of early-acting hematopoietic cytokine(s) such as Stem Cell Factor (SCF), Thrombopoietin (Tpo) together with other humoral regulators such as Wnt and BMP molecules in promoting self-renewal cell divisions in serum free culture medium. In parallel we are also employing retrovirus- mediated gene transfer technique to ectopically express nanog and constitutively activated b-catenin in PHSC and study the physiological regulator(s) conferred by the bcl-2 transgene in promoting self-renewal cell divisions.

There are ample experiments demonstrate that one can obtain various types of hematopoietic cells from the in vitro differentiation of ES cells through embryoid body formation and subsequent cellular expansion using lineage-specific cytokine(s). So far evidence for a robust production of “transplantable” primitive hematopoietic stem cells from ES cells is lacking. There are in principle at least two hurdles to be solved in achieving such a quest. Firstly there is a lack of quantitative assays to evaluate the effect of soluble growth factors and cell-cell interactions for the cell fate specification from mesoderm to hemangioblasts, and subsequent hematopoietic stem cell commitment though genetic analysis has shown that both SCL and Flk1 receptor play a vital role in the process. Secondly it is currently viewed that HSC arise de novo in the yolk sac need to be “educated” in the microenvironment(s) provided by the AGM and/or fetal liver to become those that can be successfully engrafted in the lethally irradiated adult recipients. Development of an in vitro culture system using AGM-derived stromal cells and genetic marking of meso-endodermal cells are paramount to our research goal.