A5024063071- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- Kruppel-like factors research
- CAR-T cell therapy research
- Hemoglobinopathies and Related Disorders
- Chemical Reaction Mechanisms
- Ubiquitin and proteasome pathways
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Fluorine in Organic Chemistry
- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Histone Deacetylase Inhibitors Research
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Zebrafish Biomedical Research Applications
- Genomics and Chromatin Dynamics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Galectins and Cancer Biology
- Cancer-related Molecular Pathways
National Institutes of Health
2005-2021
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2005-2021
Lanzhou University
2012
National Institute of Diabetes and Digestive and Kidney Diseases
2010
Vertebrate limb development is controlled by three signaling centers that regulate patterning and growth along the proximodistal (PD), anteroposterior (AP) dorsoventral (DV) axes. Coordination of these axes achieved interactions feedback loops involving secreted molecules mediate activities centers. However, it unknown how are processed in responding cells. We have found distinct LIM homeodomain transcription factors, encoded homeobox (LIM-HD) genes Lhx2, Lhx9 Lmx1b integrate events link...
Negative selection and regulatory T (T reg) cell development are two thymus-dependent processes necessary for the enforcement of self-tolerance, both require high-affinity interactions between receptor (TCR) self-ligands. However, it remains unclear if they similarly impacted by alterations in TCR signaling potential. We generated a knock-in allele (6F) ζ chain gene encoding mutant protein lacking capability whose expression is controlled endogenous sequences. Although negative was defective...
During erythrocyte development, the nuclear cofactor Lim domain binding protein 1 (Ldb1) functions as a core subunit of multiprotein DNA complexes that include transcription factors Scl and Gata-1 Lim-only adapter Lmo2. Scl, Gata-1, Lmo2 are each required for erythropoiesis, suggesting Ldb1-nucleated regulate key steps during erythropoiesis. We documented requirement Ldb1 in erythropoiesis mice. Analysis ldb1(-/-) embryos revealed critical primitive conditional inactivation ldb1 at later...
Analysis of the transcriptional profiles developing thymocytes has shown that T lineage commitment is associated with loss stem cell and early progenitor gene signatures acquisition signatures. Less well understood are epigenetic alterations accompany or enable these changes. Here, we show histone demethylase Lsd1 (Kdm1a) performs a key role in extinguishing stem/progenitor programs addition to repressive during thymocyte maturation. Deletion caused block late development resulted...
Abstract Thymocyte selection is controlled by signaling motifs (ITAMs) contained within the invariant T cell receptor (TCR) subunits. The current model of thymocyte posits that differences in affinity TCR for self-peptides results response, with low interactions promoting positive and high triggering negative selection. We others previously demonstrated attenuation potential (by mutation zeta chain ITAMs) leads to generation cells express auto-reactive TCRs. However, these did not cause...
Abstract The prevailing view of thymocyte selection is that the fate developing cells dictated exclusively by affinity/avidity expressed TCR for self-MHC/self-ligand. We hypothesize there significant plasticity in signaling processes control T cell development and ability to ‘fine-tune’ response, through regulated expression molecules positively or negatively impact response operates maximize repertoire. One example a ‘fine-tuning’ molecule was previously characterized surface protein CD5....
Abstract Ldb1 is a ubiquitous nuclear protein that functions by interacting with and/or recruiting specific partners (including LMO2, SCL and GATA-1) to form multi-molecular DNA-binding transcription complexes. In the hematopoietic lineage, expression of highest in lineage−Sca1+c-kit+ (LSK) multipotent progenitors. gradually decreases as cells mature within lymphoid or granulocyte/macrophage lineages, but remains high erythroid lineage cells. We investigated role hematopoiesis conditional...