A5057518210- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- NF-κB Signaling Pathways
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Immune Response and Inflammation
- DNA Repair Mechanisms
- Viral-associated cancers and disorders
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Gene expression and cancer classification
- T-cell and Retrovirus Studies
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Phagocytosis and Immune Regulation
- Galectins and Cancer Biology
- Inflammasome and immune disorders
St James's University Hospital
2018-2024
University of Leeds
2017-2024
Columbia University
2009-2018
Columbia University Irving Medical Center
2011-2017
Novartis Institutes for BioMedical Research
2013-2016
Novartis (Switzerland)
2013-2016
National Center on Addiction and Substance Abuse at Columbia University
2016
University of Florida
2016
Columbus Oncology and Hematology Associates
2016
Reckitt Benckiser (United States)
2016
Immunoglobulin (Ig)M+IgD+ B cells are generally assumed to represent antigen-inexperienced, naive expressing variable (V) region genes without somatic mutations. We report here that human IgM+IgD+ peripheral blood (PB) the CD27 cell surface antigen carry mutated V genes, in contrast CD27-negative cells. IgM+IgD+CD27+ resemble class-switched and IgM-only memory terms of phenotype, comprise ∼15% PB lymphocytes healthy adults. Moreover, a very small population (<1% cells) highly IgD-only...
B cell-derived chronic lymphocytic leukemia (B-CLL) represents a common malignancy whose cell derivation and pathogenesis are unknown. Recent studies have shown that >50% of CLLs display hypermutated immunoglobulin variable region (IgV) sequences more favorable prognosis, suggesting they may represent distinct subset which transited through germinal centers (GCs), the physiologic site IgV hypermutation. To further investigate phenotype CLLs, their cellular relationship to normal cells, we...
The molecular mechanism involved in the process of antigen-driven somatic hypermutation Ig genes is unknown, but it commonly believed that this restricted to loci. B cell lymphomas display multiple mutations clustering 5′-regulatory region BCL-6, a proto-oncogene encoding for POZ/Zinc finger transcriptional repressor expressed germinal center (GC) cells and required GC formation. To determine whether BCL-6 represent tumor-associated phenomenon or reflect physiologic mechanism, we screened...
The germinal center (GC) reaction is crucial for T cell-dependent immune responses and targeted by B cell lymphomagenesis. Here we analyzed the transcriptional changes that occur in cells during GC transit (naïve → centroblasts centrocytes memory cells) gene expression profiling. Naïve cells, characterized of cycle-inhibitory antiapoptotic genes, become inducing an atypical proliferation program lacking c-Myc expression, switching to a proapoptotic program, down-regulating cytokine,...
Peripheral T cell lymphoma, unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from normal cells. Comparison with profiles purified subpopulations (CD4+, CD8+, resting [HLA-DR–], activated [HLA-DR+]) reveals PTCLs/U are closely related peripheral lymphocytes, either CD4+ or CD8+. Interestingly, global cannot be surrogated by...
Germinal centers (GCs) are the sites where memory B cells and plasma producing high-affinity antibodies generated during T cell–dependent immune responses. The molecular control of GC cell maintenance differentiation remains incompletely understood. Activation NF-κB signaling pathway has been implicated; however, distinct roles individual transcription factor subunits unknown. We report that cell–specific deletion c-REL or RELA, which both activated by canonical pathway, abolished generation...
Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis antimicrobial expression ileum, as well colonocyte microbiota-driven chronic inflammation colon. Combined RelA, c-Rel, RelB deficiency IECs but not colitis, suggesting that NEMO prevents colon by NF-κB-independent functions....
Human naive and germinal center (GC) B cells were sorted by flow cytometry rearranged V H region genes amplified sequenced from single cells. Whereas no deletions or insertions found in cells, ≈4% of in-frame >40% out-of-frame rearrangements GC harbored and/or variable length. The pattern deletions/insertions their restriction to mutated strongly suggests that they result somatic hypermutation. Deletions account for ≈6% mutations introduced into These seem be the main cause generation...
A major challenge in DNA microarray analysis is to effectively dissociate actual gene expression values from experimental noise. We report here a detailed noise for oligonuleotide-based experiments involving reverse transcription, generation of labeled cRNA (target) through vitro and hybridization the target probe immobilized on substrate. By designing sets replicate that bifurcate at different steps assay, we are able separate caused by sample preparation processes. quantitatively...