Principal Research Scientist, Institute of Medical Engineering & Science, MIT
Jane-Jane Chen was born and raised in Taiwan. She obtained her BSc from the Department of Agricultural Chemistry, National Taiwan University in 1973. Then, she came to USA for her graduate studies and received a PhD in 1978 from the Department of Biochemistry, School of Medicine, University of Southern California. Under the mentorship of Dr. Mary Ellen Jones, Jane-Jane investigated the regulation of pyrimidine biosynthesis in mammalian cells. She had her postdoctoral training in the laboratory of Dr. Irving M. London from 1979-1987 (part-time 1981-1983, 1985-1987) at the Harvard-MIT Division of Health Sciences and Technology, MIT. She was a Research Scientist from 1987-1990 and a Principal Research Scientist from 1990-2013 at the Harvard-MIT Division of Health Sciences and Technology. Since 2013, Jane-Jane has been working as a Principal Research Scientist at the Institute for Medical Engineering and Science, MIT. She is an established principal investigator with continuous NIH funding for three decades to research heme-regulated eIF2 a kinase and erythropoiesis.
- PhD in Biochemistry, School of Medicine, University of Southern California, 1978
- BSc in Agricultural Chemistry, National Taiwan University, 1973
- Ad hoc member, NIH, Molecular and Cellular Hematology Study Section, 2013
- Member, Scientific Committee on Iron and Heme, American Society of Hematology, 2009-2010
- Panelist, NSF, Biochemistry of Gene Expression, 2003-2008
- Member, NIH, Hematology Study Section 2, 1997-2001
Jane-Jane Chen’s laboratory is among the leading groups in the translational regulation involving eIF2a kinases. Phosphorylation of eIF2a is an ancient and conserved mechanism for stress adaptation from yeast to human. We demonstrate that heme-regulated eIF2a kinase (HRI) is essential for the adaptation of iron-deficiency anemia. HRI is also necessary for the survival of b-thalassemia in mice. Phosphorylation of eIF2a by HRI not only inhibits translation globally, but also selectively increases the translation of ATF4 mRNA in primary erythroid precursors. This HRI-activated eIF2aP-ATF4 stress response pathway is necessary to mitigate oxidative stress and to promote erythroid differentiation. Both of these essential processes are compromised in b-thalassemia. Thus, components of the HRI-eIF2aP signaling pathway may be novel targets for pharmaceutical treatment of thalassemia and hemoglobinopathy generally. Beyond the erythroid lineage, HRI stress signaling pathway is also necessary for the maturation of macrophage, which plays a critical role in erythropoiesis as well as in recycling iron from senescent red blood cells for the production of next generation of red blood cells.
Current research efforts in the lab is to further understand the HRI-activated eIF2aP-ATF4 signaling in both erythroid and macrophage lineagesz during iron-restrictive erythropoiesis by using Hri-/- and Atf4-/- mice as well as the knockin mice lacking eIF2aP signaling specifically in the erythroid lineage only. We are also investigating genome-wide in vivo translational regulation during normal and stress erythropoiesis employing the recently developed ribosome profiling technique in primary erythroblasts. We anticipate uncovering novel molecular mechanisms in translational regulation and new proteins produced in the erythroid lineage during stress erythropoiesis.
- J-J Chen. “Translational Control by Heme-Regulated eIF2α Kinase during Erythropoiesis.” Curr Opin Hematol 21 (2014): 172-78.
- G. Qu, S. Liu, S. Zhang, L. Wang, X. Wang, B. Sun, N. Yin, X. Gao, T. Xia, J-J Chen, G. B. Jiang. “Graphene Oxide Induces Toll-like Receptor 4 (TLR4)-Dependent Necrosis in Macrophages.” ACS Nano 7 (2013): 5732-745.
- R. N. V. S. Suragani, R. S. Zachariah, J. G. Velazuez, S. Liu, C. Sun, T. M. Townes, and J-J Chen. “Heme-Regulated eIF2a Kinase Activated Atf4 Signaling Pathway in Oxidative Stress and Erythropoiesis.” Blood 119 (2012): 5276-84.
- P. Acharya, J-J Chen, and M. A. Correia. “Hepatic Heme-Regulated inhibitor (HRI) eukaryotic initiation factor 2alpha kinase: A protagonist of Heme-Mediated Translational Control of CYP2B Enzymes and a Modulator of Basal Endoplasmic Reticulum (ER)-Stress Tone.” Molecular Pharmacology 77 (2010): 575-92.
- S. J. Liu, R. N. V. S. Suragani, F. Wang, A. P. Han, W. T. Zhao, M. D. Fleming, N. C. Andrews, J-J Chen. “Deficiency of Heme-Regulated eIF2α Kinase Attenuates Macrophage Maturation, Inflammatory Response, and Iron Homeostasis.” Journal of Clinical Investigation 117 (2007): 3296-305.
A full list of Jane-Jane’s publication can be found on PubMed.