Member Biography

Hematopoietic cell transplantation (HCT) remains the only curative treatment for many malignant and non-malignant blood disorders. However, 30%-40% of patients will be excluded from this treatment because of not having an HLA-matched donor. Human cord blood (CB) is a feasible source of hematopoietic stem cells (HSCs) for transplantation. Human CB has a reduced need for HLA matching, which extends the treatment for nearly all patients. Besides, CB has additional advantages including ready availability, lower incidence of GvHD and lower risk of transmissible virus infection. However, CB transplantation suffers from limited numbers of HSCs in a single CB unit. To overcome this limitation, new methods to enhance CB HSC homing and expansion would be warranted. Therefore, my primary research interest is to understand the cellular and molecular factors that affect the expansion and engraftment of CB HSCs. My future research will focus on two important aspects of CB HSC function: HSC trafficking and HSC expansion. My ultimate aim is to reveal essential intrinsic and extrinsic factors that regulate CB HSC functions and eventually translate these findings to new therapeutic approaches. After intravenous infusion, HSCs migrate from peripheral blood to bone marrow niches through the circulation. Efficient HSC homing is crucial for successful clinical outcomes from HCT. Stromal cell derived factor-1 (SDF-1)/chemokine C-X-C receptor 4 (CXCR4) interactions are implicated as a critical axis regulating HSC trafficking and homing to the bone marrow environment. My previous work has identified HDAC5 as an important regulator of CXCR4 transcription and HSC homing. The results show that upon HDAC5 inhibition, acetylated p65 binds to the CXCR4 promoter region, transcriptionally upregulates CXCR4 expression and enhances homing and long-term engraftment of self-renewing human CB HSCs. To shed more light on HSC trafficking process, we will screen for i) factors involved in enhancing HSC homing by using in vitro migration assay, ii) adhesion molecules for HSC homing by studying downstream targets of HDAC5. We will also study these factors in the context of HSC mobilization or migration into peripheral blood. In HCT, higher numbers of HSCs are preferable to achieve rapid engraftment, which is important for patient survival and recovery. Improvement in the method to better expand HSC can help to obtain a large number of HSCs for clinical use. In addition, expansion of HSC would also benefit gene therapy that using genetic manipulations of HSC to cure human disease. CRISPR-Cas9 has been widely used to perform both loss-of-function and gain-of-function screen in human cells. We would like to use CRISPR-Cas9 genome editing technology to identify novel factors contributing to HSC expansion. We will also test for better HSC culture conditions by a combination of different small molecule compounds.

Post-doctoral Fellowship - Indiana University School of Medicine, Indianapolis, IN 11/2018

Post-doctoral Fellowship - National Institute of Biological Science, Beijing 06/2012

Ph.D. - National Institute of Biological Science, Beijing 06/2010