Overview
Research in our laboratory focuses on molecular mechanism of lymphocyte development and genetic basis of lymphoid diseases such as leukemia and autoimmune disorders. We are using mouse models to investigate the role of E2A and other related transcription factors in lymphocyte development and immune function. We have shown that E2A plays an essential role in regulating both B and T cell development. Mice deficient for E2A cannot produce any B cell and exhibit high incidence of T cell leukemia. Separate studies also indicated that E2A is involved in the development of autoimmune disorders. Our current and future studies are to combine genetic, molecular biology, and immunology means to determine gene expression programs during lymphocyte development.
The mechanistic studies of gene function in animal models provide important clues in understanding relevant human diseases. It has been shown that about 20-30% of pediatric acute lymphocytic leukemias (ALL) are linked to chromosomal rearrangements at the E2A gene locus. Most of these genetic defects produce oncogenic forms of E2A proteins, which are the possible cause of leukemia. The use of animal models allows us to further define the molecular events underlying the disease development. Our long term goal is to provide molecular basis for early diagnosis and treatment of relevant lymphoid system diseases.
Laboratory website: Http://sites.duke.edu/zhuanglab.
The mechanistic studies of gene function in animal models provide important clues in understanding relevant human diseases. It has been shown that about 20-30% of pediatric acute lymphocytic leukemias (ALL) are linked to chromosomal rearrangements at the E2A gene locus. Most of these genetic defects produce oncogenic forms of E2A proteins, which are the possible cause of leukemia. The use of animal models allows us to further define the molecular events underlying the disease development. Our long term goal is to provide molecular basis for early diagnosis and treatment of relevant lymphoid system diseases.
Laboratory website: Http://sites.duke.edu/zhuanglab.
Current Appointments & Affiliations
Professor of Integrative Immunobiology
·
2011 - Present
Integrative Immunobiology,
Basic Science Departments
Professor of Molecular Genetics and Microbiology
·
2011 - Present
Molecular Genetics and Microbiology,
Basic Science Departments
Member of the Duke Cancer Institute
·
1995 - Present
Duke Cancer Institute,
Institutes and Centers
Recent Publications
E proteins control the development of NKγδT cells through their invariant T cell receptor.
Journal Article Nat Commun · June 13, 2024 T cell receptor (TCR) signaling regulates important developmental transitions, partly through induction of the E protein antagonist, Id3. Although normal γδ T cell development depends on Id3, Id3 deficiency produces different phenotypes in distinct γδ T ce ... Full text Link to item CiteE protein binding at the Tcra enhancer promotes Tcra repertoire diversity.
Journal Article Front Immunol · 2023 V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4+CD8+ double positive (DP) thymocytes and requires the Tcra enhancer (Eα). E proteins a ... Full text Link to item CiteLoss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes.
Journal Article Nat Commun · October 6, 2022 Production of a functional peripheral T cell compartment typically involves massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment of double-ne ... Full text Link to item CiteRecent Grants
E2A/HEB MEDIATED TRANSCRIPTIONAL REGULATION IN T CELL DEVELOPMENT
ResearchPrincipal Investigator · Awarded by National Institutes of Health · 1999 - 2022Regulation of the type 1 program during ILC3 plasticity
FellowshipCo-Sponsor · Awarded by National Institutes of Health · 2020 - 2022Organization and Function of Cellular Structure
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 1975 - 2020View All Grants
Education, Training & Certifications
Yale University ·
1989
Ph.D.