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Immunobiology and Cancer Research Program

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OMRF research could curb infections in the elderly

Xiao-Hong Sun, Ph.D. Member, Immunobiology and Cancer Research Program Eli Lilly Distinguished Chair in Biomedical Research Adjunct Professor, Departments of Microbiology and Immunology and Cell   Biology, University of Oklahoma Health Sciences Center

Research Interests
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.

Joined OMRF Scientific Staff in 1999.

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

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