Biography
Dr. Zhu has been focused on hematopoiesis specially the human γ-globin gene expression and γ- to β-globin switch with a goal to develop treatment strategies for hemoglobinopathies. Dr. Zhu received training from the Hemoglobinopathy Translational Research Skills Core (HTRC), a research career training opportunity funded by the National Heart Lung and Blood Institute (NHLBI), which aimed at increasing the number of junior investigators conducting independent hemoglobinopathy research. Dr. Zhu’s laboratory received NIH R01s to investigate globin gene expression and oxidative stress response to explore the mechanism of SCD and its treatment strategy.
Research Interests
NRF2 functions in SCD
Using human erythroid primary cells and an NRF2 knockout SCD mouse model, the research in Dr. Zhu’s lab will determine the important role of NRF2 in developmentally regulated hemoglobin switching during SCD development. Major research focus includes: 1) the role of NRF2 in the regulation of globin gene expression and switching. 2) Studies of the deleterious effect of downregulated NRF2 in SCD patient’s erythroid progenitor cells. 3) Mechanisms of the metabolic dysregulation of SCD during erythropoiesis in both human patients and animal models. 4) explore small chemical compounds that could improve the metabolism of erythroblasts. To achieve these objectives, the laboratory has applied multiomic strategies including epigenetic, transcriptomic, and metabolic studies to reveal the detailed molecular mechanism for NRF2 in human globin gene regulation and their relevance for the treatment of SCD.
NRF2 functions in tumors
A specific focus on NRF2 function in liver tumors is also currently under investigation in Dr. Zhu’s laboratory. Cancer cells experience aberrant epigenetic modification, especially for histone acetylation in solid tumors. One regulatory mechanism for histone acetylation is the availability of acetyl CoA as the source of the acetyl group to incorporate into lysine residues. Research in the lab demonstrates that NRF2 dictates metabolic reprogramming by regulating acetyl CoA availability to modulate metabolic energy generation for tumor cell growth and histone acetylation. The findings in Dr. Zhu’s lab imply that NRF2, in addition to its typical regulatory role on reactive oxygen species response, integrates metabolic and epigenetic programs to drive liver tumor progression.