Dr. Jeffrey J. Y. Yen, Professor

Institute of Biomedical Sciences, Academia Sinica
Phone: 886-2-2789-9017
E-mail: bmjyen@ibms.sinica.edu.tw


Ph.D.@Baylor College of Medicine, USA


@The long term interest of my laboratory has been on the growth and death regulation of hematopoietic cell lineages due to the underlying mechanism may shed lights on many human detrimental diseases, including leukemia, immunodeficiencies, allergic disorders, asthma, and autoimmunities.

@In the past ten years, we have applied standard molecular and cellular biology techniques to pursue our goals in terms of involvement of specific genes in the death regulation of hematopoietic cells. We continued to work on the molecular mechanism triggering the programmed cell death when cytokine was depleted. A novel cytokine receptor associated signaling molecule as well as a novel cytokine deprivation-induced early gene are identified. They both were found to be strongly apoptogenic to hematopoietic cells, suggesting the likelihood of the involvement of these novel molecules in this process. On the other hand, we discovered the involvement of the erythroid transcriptional factor GATA-1 in transducing anti-apoptotic acitivity of interleukin 3 in cytokine dependent hematopoietic cell line. Intriguingly, there is a strong correlation between tissue expression profile of GATA family members and their target anti-apoptotic gene E4BP4, suggesting the survival effect of GATA family proteins may play an important role in multiple organ development.

@In the new millennium, we also included molecular genetic and functional genomic approaches to tackle the regulatory mechanism of apoptosis control. We are currently actively participating in the genome-wide phenotype-driven ENU-mutagenized mice screening program for the hematopoietic deficiency phenotype. Once the mutation is confirmed and chromosomal location is mapped, high-resolution genetic mapping and molecular cloning of the defected gene will be pursued using various genomic research tools, such as SNP discovery, bioinformatics and transgenic rescue. We are at present working on a mutant mouse line with segmental progeroid symdrome and another line with lymphocytopenia and combined immune deficiency. Our preliminary study suggested that both mutations affect the survival of either stem cell population or lymphoid cell lineages.


1. Huang, H.M., Li, J.C., Hsieh, Y.C., Yang-Yen, H.F. and Yen, J.J.Y.

2. Optimal proliferation of a hematopoietic progenitor cell line requires either costimulation with stem cell factor or increase of receptor expression that can be replaced by overexpression of Bcl-2. Blood 93: 2569-2577, 1999.

3. Lee, S.F., Huang, H.M., Chao, J.R., Lin, S., Yang-Yen, H.F. and Yen, J.J.Y.

4. Cytokine receptor common a chain as a potential activator of cytokine withdrawal-induced apoptosis. Mol. Cell. Biol. 19: 7399-7409, 1999.

5. Huang, H.M., Huang, C.J. and Yen, J.J.Y.

6. Mcl-1 is a common target of stem cell factor and interleukin 5 for apoptosis prevention activity via MEK/MAPK and PI-3K/Akt pathways. Blood 96: 1764-1771, 2000.

7. Chen, W., Yu, Y.L., Lee, S.F., Chiang, Y.J., Chao, J.R., Huang, J.H., Chiong, J.H., Huang, C.J., Lai, M.Z., Yang-Yen, H.F. and Yen, J.J.Y.

8. CREB is one component of the binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the IL-3 survival signal. Mol. Cell. Biol. 21: 4636-4646, 2001.

9. Yu, Y.L., Chiang, Y.J., and Yen, J.J.Y. GATA factors are essential for transcription of the survival gene E4BP4 and the viability response of interleukin-3 in Ba/F3 hematopoietic cells. J. Biol. Chem.277:27144-27153, 2002.

Members of Laboratory