Dr. Jane-Jane Chen

Jane-Jane Chen has been a PI (Principal Investigator) with successful records in securing RO1 grants from National Institutes of Health (NIH) and National Science Foundation (NSF) for the past 20 years. Chen's laboratory is among the leading groups in the translational regulation involving eIF2± kinases. We have cloned the cDNA, genomic DNA of heme-regulated eIF2± kinase (HRI). We have investigated the molecular mechanism of regulation of HRI by heme and autophosphorylation biochemically. Chen's lab has also generated the HRI knockout mice. Using HRI null mice we have demonstrated that HRI is essential for the adaptation of microcytic and hypochromic anemia and the survival of erythroid precursors in iron deficiency.

Most recently through crossing of HRI knockout mice with mouse models of red cell and iron homeostasis disorders, we have established the novel essential protective role of HRI in two red cells disorders, beta thalassemia and erythropoietic protoporphyria. We have performed gene profiling experiments using whole mouse expression gene chips to identify the maser genes regulated by HRI in erythroid proliferation and differentiation as well as in iron homeostasis. We have also found that HRI expression is necessary for macrophage maturation and cytokine production in response to LPS. Interestingly, serum BMP2 level is significantly lower in HRI knockout mice. Recently, we have found that HRI activated stress signaling pathway is not only necessary to mitigate oxidative stress , but also is necessary for erythroid differentiation especially under stress conditions. Through small chemical screens for modulation of HRI signaling pathway during oxidative stress , a natural product that specifically regulate HRI was discovered. This HRI specific compound may provide a potential alternative treatment for many anemia associated with ineffective erythropoiesis.


(summary updated 11/2011)