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Sun, Xiao-Hong

Xiao-Hong Sun, Ph.D.

Xiao-Hong Sun, Ph.D.

Member
Immunobiology & Cancer Research Program

Lew and Myra Ward Chair in Biomedical Research

Adjunct Professor, Departments of Microbiology & Immunology and Cell Biology, University of Oklahoma Health Sciences Center

The human body craves balance. All of our biological systems work (or should work) in concert to keep us healthy. One imbalance can send ripple effects throughout the body, causing disease and sometimes death.

In my lab, we study a protein called Notch, which functions as a decision-maker. It’s vital to life. Too little of it, and we wouldn’t be born—but too much of it can lead to cancer.

One important role of Notch is in the development of the immune system. White blood cells come from stem cells, but at a certain point, they have a decision to make—whether to become B cells, T cells or bacteria-eating macrophages. Notch plays a similar role in the body, keeping the balance to help regulate other functions. But an excess of Notch can lead to cancer, including leukemia.

We are particularly interested in how Notch performs regulatory functions in normal development and in diseases. For example, we found that Notch breaks down other proteins to influence how cells divide and develop. They can direct cell lineage depending on which proteins they break down at what times and in what locations.

Only by studying the chain of events that leads from Notch to cancer can we hope to find a way to inhibit the dangerous effects of Notch without stopping its natural, healthy regulation.

Education
Ph.D., Cornell University, Ithaca, New York, 1987

Honors and Awards
1989-1991 Cancer Research Institute Postdoctoral Fellowship
1992-1996 Cancer Research Institute Investigator Award
1994-1998 Irma T. Hirschl Trust Career Scientist Award
2002-2005 S. Graham Smith Distinguished Scientist Award

Other Activities
Reviewer for Immunity, Nature Genetics and Nature Immunology
Member of Scientific Advisory Committee of the Damon Runyon Cancer Research Foundation
Member of the NIH CMI-B study section

Memberships
American Association for the Advancement of Science
American Association of Immunologists
Society of Chinese Bioscientists in America

Joined OMRF Scientific Staff in 1999.

The basic helix-loop-helix family of proteins represented by the E2A transcription factor is crucial for the development of both B and T lymphocytes, as well as for the suppression of leukemogenesis. Therefore, mechanisms controlling the function of E2A proteins are important subjects of study. Previously, we have found two classes of proteins that function as inhibitors of E2A proteins, namely the Id and Tal proteins. We have developed transgenic mouse models, in which these inhibitors are expressed, to study the role of E2A in T cell development. Data accumulated in the last decade allowed us to formulate a hypothesis that E2A controls the threshold of pre-T or T-cell receptor stimulation and thereby ensures proper T-cell development and prevents leukemogenesis. We continue to use these mouse models to address the molecular mechanisms by which E2A controls the threshold of stimulation. We have also identified new E2A target genes by combining inducible gene expression and DNA microarray.

Recently, we made a novel connection between the Notch signaling pathway and the ubiquitin-mediated degradation of several important regulatory proteins including E2A transcription factors and JAK kinases. Since the Notch signaling pathway is crucial for several lineage choices during lymphocyte development, our finding of Notch-induced E2A degradation could explain how these decisions are implemented. This finding also sheds light on the mechanism by which abnormal activation of Notch signaling pathways causes leukemia. Along this line of investigation, we have also demonstrated that one of the Notch target genes, HES1, synergizes with the loss of E2A function in leukemogenesis.

Furthermore, we have created a mouse model in which green fluorescent protein (GFP) is expressed in place of Id1. Using this mouse model, we have shown that Id1 is important for the maintenance of the size of hematopoietic stem cell pool and for the differentiation of myeloid lineage cells. Using GFP as a marker, we were able to visualize various stem or progenitor cells, which will greatly facilitate our investigations in the areas of hematopoiesis, angiogenesis and hair regeneration.

Recent Publications

* Hu T, Wang H, Simmons A, Bajana S, Zhao Y, Kovats S, Sun XH, Alberola-Ila J. Increased Level of E Protein Activity during Invariant NKT Development Promotes Differentiation of Invariant NKT2 and Invariant NKT17 Subsets. J Immunol 2013. [Abstract] EPub

Zhang P, Zhao Y, Sun XH. Notch-Regulated Periphery B Cell Differentiation Involves Suppression of E Protein Function. J Immunol  191:726-736, 2013. [Abstract]

Liu C, Jin R, Wang HC, Tang H, Liu YF, Qian XP, Sun XY, Ge Q, Sun XH, Zhang Y. Id1 expression promotes peripheral CD4 T cell proliferation and survival upon TCR activation without co-stimulation. Biochem Biophys Res Commun 2013. [Abstract] EPub

Selected Publications

Zhao Y, Ling F, Wang HC, Sun XH. Chronic TLR Signaling Impairs the Long-Term Repopulating Potential of Hematopoietic Stem Cells of Wild Type but Not Id1 Deficient Mice. PLoS One 8:e55552, 2013. [Abstract]

Wang HC, Peng V, Zhao Y, Sun XH. Enhanced notch activation is advantageous but not essential for T cell lymphomagenesis in Id1 transgenic mice. PLoS One 7:e32944, 2012. [Abstract]

Wu W, Sun XH. A mechanism underlying NOTCH-induced and ubiquitin-mediated JAK3 degradation. J Biol Chem 286:41153-41162, 2011. [Abstract]

Nie L, Zhao Y, Wu W, Yang YZ, Wang HC, Sun XH.  Notch-induced Asb2 expression promotes protein ubiquitination by forming non-canonical E3 ligase complexes. Cell Res 21:754-769, 2011. [Abstract]

Wang HC, Perry SS, Sun XH.  Id1 attenuates Notch signaling and impairs T-cell commitment by elevating Deltex1 expression. Mol.Cell Biol. 29:4640-4652, 2009. [Abstract]

Cochrane SW, Zhao Y, Welner RS, Sun XH.  Balance between Id and E proteins regulates myeloid-versus-lymphoid lineage decisions. Blood 113:1016-1026, 2009. [Abstract]

View all publications in PubMed

Immunobiology and Cancer Research Program, MS 29
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104

Phone: (405) 271-7103
Fax: (405) 271-7128
E-mail: Xiao-Hong-Sun@omrf.org

Hongcheng Wang, Ph.D.
Associate Staff Scientist

Bin Kang, Ph.D.
Assistant Staff Scientist

Flora Ling
Graduate Student

Wei Wu
Graduate Student

Ying Zhao
Manager Laboratory

Mary Flynn
Executive Assistant