Hai-Hui (Howard) Xue, M.D., Ph.D.
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Assistant Professor of Microbiology Campus address: 3-710 BSB Mailing address: 51 Newton Rd. 3-710 Bowen Science Building Iowa City, IA 52242 Phone: 319-335-7937 Email: |
M.D., China Medical University, 1991; Ph.D., Hamamatsu University School of Medicine, 2000
Transcriptional control of hematopoietic stem cell self-renewal and its differentiation to antigen-responding T cells
The identity of a cell type is determined by genes it expresses, where transcriptional regulation plays a central role. Differentiation of hematopoietic stem cells (HSCs) to antigen responding T cells is accompanied by many stages of cell identity transition. Our lab aims to decode how key transcription factors maintain the cell identity and instigate the transitions during the following biological processes:
- self-renewal of HSCs to maintain a constant supply of multiple blood lineages throughout lifetime, and how aging affects HSC maintenance and multipotency;
- T cell development in the thymus from immature progenitors, and how developing thymocytes, which are highly proliferative and are accompanied by constant DNA break and repair during the recombination process, are safeguarded from malignant transformation;
- transition of antigen-specific effector T cells to memory T cells to form stable immunological memory.
Our current focus is on two groups of transcription factors, GABP and TCF-1/LEF-1. GABP (GA binding protein) subunits and isoforms demonstrated relative stable expression in all the processes described above, however, along with the identity transition, GABP adapts well and assumes different roles. On the other hand, TCF-1/LEF-1 expression and activity are regulated in response to extracellular Wnt signaling. We are using molecular biology, genomic, proteomic, and bioinformatic approaches to decipher the interplay of these key transcription factors in these hematological/immunological processes.
Recent publications
Yu, S., Zhou, X., Hsiao, J.J., Yu, D., Saunders, T.L., and Xue, H.H. Fidelity of a BAC-EGFP transgene in reporting dynamic expression of IL-7α in T cells. Transgenic Res. (in press).
Yu, S., Cui, K., Jothi, R., Zhao, D.M., Jing, X., Zhao, K., and Xue, H.H. GABP controls a critical transcription regulatory module that is essential for maintenance and differentiation of hematopoietic stem/progenitor cells. Blood. 117:2166-2178, 2011.
Zhou, X., Yu, S., Zhao, D.M., Harty, J.T., Badovinac, V.P., Xue, H.H. Differentiation and persistence of memory CD8 T cells depend on T cell factor 1. Immunity. 33: 229-240, 2010. [Preview by Paley and Wherry. TCF-1 flips the switch on Eomes. Immunity. 2010, 33: 145-147.]
Yu, S., Zhao, D.M., Jothi, R., and Xue, H.H. Critical requirement of GABPalpha for normal T cell development. J. Biol. Chem. 285: 10179-10188, 2010.
Zhao, D.M., Yu, S., Zhou, X., Haring, J.S., Held, W., Badovinac, V.P., Harty, J.T., and Xue, H.H. Constitutive activation of Wnt signaling pathways favors generation of memory T cells. J. Immunol. 184: 1191-1199, 2010.
Jing, X., Zhao, D.M., Waldschmidt, T., and Xue, H.H. GABPbeta2 is dispensable for normal lymphocyte development but moderately affects B cell responses. J. Biol. Chem. 283: 24326-24333, 2008.