A5005150881- Fibromyalgia and Chronic Fatigue Syndrome Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Celiac Disease Research and Management
- Vitamin C and Antioxidants Research
- Diabetes and associated disorders
- Renal Transplantation Outcomes and Treatments
- Microscopic Colitis
- Exercise and Physiological Responses
- Complementary and Alternative Medicine Studies
- Metabolism and Genetic Disorders
- Dermatological and Skeletal Disorders
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Tracheal and airway disorders
- Drug Transport and Resistance Mechanisms
- Vitamin D Research Studies
- Polyomavirus and related diseases
- Autoimmune and Inflammatory Disorders Research
- Hematological disorders and diagnostics
- Tryptophan and brain disorders
- Otitis Media and Relapsing Polychondritis
- Connective tissue disorders research
- Drug-Induced Hepatotoxicity and Protection
- Transplantation: Methods and Outcomes
Weill Cornell Medicine
2024
Cornell University
2024
New York Genome Center
2024
University of California, San Francisco
2019-2023
Columbia University
2023
National Institutes of Health
2023
National Cancer Institute
2023
Columbia University Irving Medical Center
2016-2018
Wheat gluten and related proteins can trigger an autoimmune enteropathy, known as coeliac disease, in people with genetic susceptibility. However, some individuals experience a range of symptoms response to wheat ingestion, without the characteristic serological or histological evidence disease. The aetiology mechanism these are unknown, no biomarkers have been identified. We aimed determine if sensitivity absence disease is associated systemic immune activation that may be linked...
Abstract Thymocytes bearing autoreactive T cell receptors (TCRs) are agonist-signaled by TCR/co-stimulatory molecules to either undergo clonal deletion or differentiate into specialized regulatory (T reg ) effector eff CD4 + cells. How these different fates achieved during development remains poorly understood. We now document that and differentiation at times thymic selection cells both arise after as alternative lineage of CD25 precursors. Disruption agonist signaling induces precursors...
Abstract Somatic evolution leads to the emergence of clonal diversity across tissues with broad implications for human health. A striking example somatic is VEXAS (Vacuoles E1 enzyme X-linked Autoinflammatory Somatic) syndrome, caused by UBA1 mutations in hematopoietic stem cells (HSCs), inducing treatment-refractory, systemic inflammation. However, mechanisms that lead survival and expansion mutant HSCs are unknown, limiting development effective therapies. The lack animal or cellular...
A persistent concern with CRISPR-Cas9 gene editing has been the potential to generate mutations at off-target genomic sites. While CRISPR-engineering mice delete a ~360 bp intronic enhancer, here we discovered founder line that had marked immune dysregulation caused by 24 kb tandem duplication of sequence adjacent on-target deletion. Our results suggest unintended repair cuts can cause pathogenic "bystander" escape detection routine targeted genotyping assays.
The etiology and mechanism of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are poorly understood no biomarkers have been established. Specifically, the relationship between immunologic, metabolic, gastrointestinal abnormalities associated with ME/CFS their relevance to established symptoms condition remain unclear. Relying on data from two independent pairs control cohorts, one at rest undergoing an exercise challenge, we identify a state suppressed acute-phase innate immune...
The majority of genetic variants associated with complex human autoimmune diseases reside in enhancers 1–3 , non-coding regulatory elements that control gene expression. In contrast directly alter protein-coding sequences, enhancer are predicted to tune expression modestly and function specific cellular contexts 4 suggesting small alterations the functions key immune cell populations sufficient shape disease risk. Here we tested this concept by experimentally perturbing distinct governing...
Genetic variants associated with human autoimmune diseases commonly map to non-coding control regions, particularly enhancers that function selectively in immune cells and fine-tune gene expression within a relatively narrow range of values. How such modest, cell-type-selective changes can meaningfully shape organismal disease risk remains unclear. To explore this issue, we experimentally manipulated species-conserved the disease-associated IL2RA locus studied accompanying progression...