Microbiology

Hai-Hui Xue, MD, PhD

Portrait

Associate Professor of Microbiology

Contact Information

Office: 3-772 Bowen Science Building
51 Newton Rd
Iowa City, IA 52242
Office Phone: 319-335-7937

Lab: 3-701 Bowen Science Building
51 Newton Rd
Iowa City, IA 52242
Phone: 319-335-7982

Email: hai-hui-xue@uiowa.edu

Education

MD, Medicine, China Medical University
Master in Medical Sciences, Biochemistry, China Medical University
PhD, Biochemistry, Hamamatsu University School of Medicine

Post Doctoral, Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Microbiology Graduate Program
Interdisciplinary Graduate Program in Immunology
Medical Scientist Training Program

Research Summary

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:

1. self-renewal of HSCs to maintain a constant supply of multiple blood lineages throughout lifetime, and how aging affects HSC maintenance and multipotency;

2. 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; and

3. 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.

Center, Program and Institute Affiliations

Center for Immunology and Immune-based Diseases
Holden Comprehensive Cancer Center

All Publications

Duong K, Das S, Yu S, Barr J, Jena S, Kim E, Zavazava N, Colgan J, Xue H, Levasseur D.  Identification of hematopoietic-specific regulatory elements from the CD45 gene and use for lentiviral tracking of transplanted cells.  Exp Hematol.  2014 September. 42(9):761-72.e1-10.
[Link]

Steinke F, Xue H.  From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells.  Immunol Res.  2014 August. 59(1-3):45-55.
[Link]

Steinke F, Yu S, Zhou X, He B, Yang W, Zhou B, Kawamoto H, Zhu J, Tan K, Xue H.  TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells.  Nat Immunol.  2014 July. 15(7):646-56.
[Link]

Xie W, Lynch T, Liu X, Tyler S, Yu S, Zhou X, Luo M, Kusner D, Sun X, Yi Y, Zhang Y, Goodheart M, Parekh K, Wells J, Xue H, Pevny L, Engelhardt J.  Sox2 modulates Lef-1 expression during airway submucosal gland development.  Am J Physiol Lung Cell Mol Physiol.  2014 April 1. 306(7):L645-60.
[Link]

Starbeck-Miller G, Xue H, Harty J.  IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo.  J Exp Med.  2014 January 13. 211(1):105-20.
[Link]

Yu S, Xue H.  TCF-1 mediates repression of Notch pathway in T lineage-committed early thymocytes.  Blood.  2013 May 9. 121(19):4008-9.
[Link]

Yu S, Zhou X, Steinke F, Liu C, Chen S, Zagorodna O, Jing X, Yokota Y, Meyerholz D, Mullighan C, Knudson C, Zhao D, Xue H.  The TCF-1 and LEF-1 Transcription Factors Have Cooperative and Opposing Roles in T Cell Development and Malignancy.  Immunity.  2012 November 16. 37(5):813-26.
[Link]

Zhou X, Xue H.  Cutting edge: generation of memory precursors and functional memory CD8+ T cells depends on T cell factor-1 and lymphoid enhancer-binding factor-1.  J Immunol.  2012 September 15. 189(6):2722-6.
[Link]

Yu S, Jing X, Colgan J, Zhao D, Xue H.  Targeting tetramer-forming GABPβ isoforms impairs self-renewal of hematopoietic and leukemic stem cells.  Cell Stem Cell.  2012 August 3. 11(2):207-19.
[Link]

Yu S, Zhou X, Hsiao J, Yu D, Saunders T, Xue H.  Fidelity of a BAC-EGFP transgene in reporting dynamic expression of IL-7Rα in T cells.  Transgenic Res.  2012 February. 21(1):201-15.
[Link]

Xue H, Zhao D.  Regulation of mature T cell responses by the Wnt signaling pathway.  Ann N Y Acad Sci.  2012 January. 1247:16-33.
[Link]

Yu S, Cui K, Jothi R, Zhao D, Jing X, Zhao K, Xue H.  GABP controls a critical transcription regulatory module that is essential for maintenance and differentiation of hematopoietic stem/progenitor cells.  Blood.  2011 February 17. 117(7):2166-78.
[Link]

Zhou X, Yu S, Zhao D, Harty J, Badovinac V, Xue H.  Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1.  Immunity.  2010 August 27. 33(2):229-40.
[Link]

Wirth T, Xue H, Rai D, Sabel J, Bair T, Harty J, Badovinac V.  Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation.  Immunity.  2010 July 23. 33(1):128-40.
[Link]

Yu S, Zhao D, Jothi R, Xue H.  Critical requirement of GABPalpha for normal T cell development.  J Biol Chem.  2010 April 2. 285(14):10179-88.
[Link]

Zhao D, Yu S, Zhou X, Haring J, Held W, Badovinac V, Harty J, Xue H.  Constitutive activation of Wnt signaling favors generation of memory CD8 T cells.  J Immunol.  2010 February 1. 184(3):1191-9.
[Link]

Wu Z, Xue H, Bernard J, Zeng R, Issakov D, Bollenbacher-Reilley J, Belyakov I, Oh S, Berzofsky J, Leonard W.  The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15Ralpha function but is not required for trans-presentation.  Blood.  2008 December 1. 112(12):4411-9.
[Link]

Jing X, Zhao D, Waldschmidt T, Xue H.  GABPbeta2 is dispensible for normal lymphocyte development but moderately affects B cell responses.  J Biol Chem.  2008 September 5. 283(36):24326-33.
[Link]

Xue H, Jing X, Bollenbacher-Reilley J, Zhao D, Haring J, Yang B, Liu C, Bishop G, Harty J, Leonard W.  Targeting the GA binding protein beta1L isoform does not perturb lymphocyte development and function.  Mol Cell Biol.  2008 July. 28(13):4300-9.
[Link]

Haring J, Jing X, Bollenbacher-Reilley J, Xue H, Leonard W, Harty J.  Constitutive expression of IL-7 receptor alpha does not support increased expansion or prevent contraction of antigen-specific CD4 or CD8 T cells following Listeria monocytogenes infection.  J Immunol.  2008 March 1. 180(5):2855-62.
[Link]

Crook M, Olive M, Xue H, Langenickel T, Boehm M, Leonard W, Nabel E.  GA-binding protein regulates KIS gene expression, cell migration, and cell cycle progression.  FASEB J.  2008 January. 22(1):225-35.
[Link]

Xue H, Bollenbacher-Reilley J, Wu Z, Spolski R, Jing X, Zhang Y, McCoy J, Leonard W.  The transcription factor GABP is a critical regulator of B lymphocyte development.  Immunity.  2007 April. 26(4):421-31.
[Link]

Pang L, Xue H, Szalai G, Wang X, Wang Y, Watson D, Leonard W, Blobel G, Poncz M.  Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins.  Blood.  2006 October 1. 108(7):2198-206.
[Link]

Leonard W, Xue H.  Interleukin-7.  Oxford: Elsevier.  2006. 

Wu Z, Kim H, Xue H, Liu H, Zhao K, Leonard W.  Interleukin-21 receptor gene induction in human T cells is mediated by T-cell receptor-induced Sp1 activity.  Mol Cell Biol.  2005 November. 25(22):9741-52.
[Link]

Xue H, Bollenbacher J, Rovella V, Tripuraneni R, Du Y, Liu C, Williams A, McCoy J, Leonard W.  GA binding protein regulates interleukin 7 receptor alpha-chain gene expression in T cells.  Nat Immunol.  2004 October. 5(10):1036-44.
[Link]

Xue H, Fink D, Zhang X, Qin J, Turck C, Leonard W.  Serine phosphorylation of Stat5 proteins in lymphocytes stimulated with IL-2.  Int Immunol.  2002 November. 14(11):1263-71.
[Link]

Xue H, Kovanen P, Pise-Masison C, Berg M, Radovich M, Brady J, Leonard W.  IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes.  Proc Natl Acad Sci U S A.  2002 October 15. 99(21):13759-64.
[Link]

Xue H, Zhao D, Suda T, Uchida C, Oda T, Chida K, Ichiyama A, Nakamura H.  Store depletion by caffeine/ryanodine activates capacitative Ca(2+) entry in nonexcitable A549 cells.  J Biochem.  2000 August. 128(2):329-36.
[Link]

Zhao D, Xue H, Chida K, Suda T, Oki Y, Kanai M, Uchida C, Ichiyama A, Nakamura H.  Effect of erythromycin on ATP-induced intracellular calcium response in A549 cells.  Am J Physiol Lung Cell Mol Physiol.  2000 April. 278(4):L726-36.
[Link]

Ichiyama A, Xue H, Oda T, Uchida C, Sugiyama T, Maeda-Nakai E, Sato K, Nagai E, Watanabe S, Takayama T.  Oxalate synthesis in mammals: properties and subcellular distribution of serine:pyruvate/alanine:glyoxylate aminotransferase in the liver.  Mol Urol.  2000. 4(4):333-40.
[Link]

Xue H, Sakaguchi T, Fujie M, Ogawa H, Ichiyama A.  Flux of the L-serine metabolism in rabbit, human, and dog livers. Substantial contributions of both mitochondrial and peroxisomal serine:pyruvate/alanine:glyoxylate aminotransferase.  J Biol Chem.  1999 June 4. 274(23):16028-33.
[Link]

Xue H, Fujie M, Sakaguchi T, Oda T, Ogawa H, Kneer N, Lardy H, Ichiyama A.  Flux of the L-serine metabolism in rat liver. The predominant contribution of serine dehydratase.  J Biol Chem.  1999 June 4. 274(23):16020-7.
[Link]

Yu B, Xue H, Yang Y, Zhao T, Zong Z.  A novel protein kinase C inhibitor in bovine spermatozoa and its effects on the development of fertilized ova.  Biomed Res (Tokyo).  1995. 16:155-63.

Date Last Modified: 06/07/2014 - 21:56:23