Danith H. Ly Research Stem Cells

Human Embryonic and Adult Stem Cells

A breakthrough in isolating and culturing human embryonic stem (ES) cells has set off waves of optimism in the public and scientific community. Much of this excitement lies in their potential to differentiate into all cell types in an organism, and even more promising, ES cells have been shown to undergo indefinite self-renewal. The implication for ES cells in cell-transplant therapy for treating human diseases is enormous, ranging from generation of new neurons for treating patients with neurodegenerative diseases such as Parkinson’s and Alzheimer’s to curing genetic defects. Beside the overwhelming potential benefits to human health, ES cells may hold secrets to our understanding of developmental biology, aging and other processes. However, before the full potential of ES cells could be realized and their medical applications be fully implemented, there are a number of fundamental problems that need to be resolved. These include: (a) maintaining uncommitted self-renewal, (b) establishing a non-destructive method for identifying ESC and intermediate stem cells, (c) regulating ESC differentiation, and (d) understanding their cellular network at the molecular level.

A number of fascinating questions need to be addressed. For example, what makes ESC totipotent? What triggers ESC to differentiate? What determines the ESC fate? Can the intermediate stem cells such as HSC, MSC, CNS-SC, NS-SC and so forth, dedifferentiate to ESC or transdifferentiate (cross lineage from one stem cell type to another) from HSC to MSC, and vice versa? These questions exemplify a gap in our knowledge about ESC. The fundamentals that can be learned from ESC may hold keys to unlocking the secrets of life and provide new avenues for future medicine.

Elucidating the Genetic Blueprint of Biology, Genentic Bioinformatics, Chemistry.

Research Interests

Our research program concentrates on four areas: (a) defining a condition for maintaining ESC self-renewal in the absence of feeder layer, (b) identifying the genetic markers unique for each stem cell lineage, particularly those intermediate stem cells found in the adult, (c) elucidating the genetic pathways that control ESC proliferation and differentiation, and (d) characterizing the cell cycle of ESC, and determining how and why it is different from that of the other progenitor cells. The ultimate question that we would like to address is: can terminal differentiated cells dedifferentiate? If they do, how far can they go up the differentiation ladder and can we regulate them?

References
1. J. A. Thomson et al., Science, 282, 1145 (1998).
2. F. M. Watt and B. L. M. Morgan, Science, 287, 1427 (2000).
3. R. McKay, Nature, 406, 361 (2000). D. Perry, Science, 287, 1423 (2000).
4. J. Nichols et al., Cell, 95, 379 (1998).
5. J. D. Flax et al., Nat. Biotech., 16, 1033 (1998). G. C. Kopen et al., Proc. Natl. Acad. Sci. USA., 96, 10711 (1999).
6. C. R. R. Bjornson et al., Science, 283, 534 (1999).

Collaborator:
Professor Martin Pera (Monash Unversity, Australia)