Expertise

His research focuses on hematopoietic stem cells and pathogenesis of hematological malignancies.

 

The long-term goal of our research is to identify novel regulators of hematopoietic stem cells (HSCs), to understand the molecular mechanisms controlling their function and develop novel therapeutic strategies to eliminate leukemia-initiating cells (LICs). We plan to pursue two projects listed below: 1. Regulation of Bmi1 function (HSC self-renewal) by the PI3K-Akt signaling pathway in normal and leukemic hematopoiesis. The PI3K/PTEN/Akt pathway has been implicated in HSC maintenance. However, the downstream target of this pathway that regulates HSC self-renewal has not been identified. We found that PKB/Akt phosphorylates Bmi1 at serine 316 in vivo, which results in its dissociation from chromatin and in de-repression of the Ink4a-Arf locus. We hypothesize that activation of PI3K/Akt pathway impairs HSC maintenance through phosphorylation and inactivation of Bmi1. 2. The role of tumor suppressor p53 in normal and leukemic hematopoiesis. The p53 gene is most frequently mutated in solid tumors (50%). In hematological malignancies, p53 mutations are less frequent (10%). Correlations between drug resistance, altered apoptosis, and mutations in p53 are found in hematological malignances. Therefore, further study is needed to determine whether p53 mutations (including H179Y, R243W, R273H and R175H) that contribute to chemotherapy and radiation therapy resistance, will still promote HSC quiescence.

 

Communities
Oncology, Pediatrics, Pediatrics
Degrees
PhD, University of the Chinese Academy of Sciences, Molecular Biology, 1997
BA, Jilin University, Biochemistry, 1992