A5101492827- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Neurobiology and Insect Physiology Research
- RNA modifications and cancer
- Physiological and biochemical adaptations
- Cancer-related molecular mechanisms research
- Animal Genetics and Reproduction
- Phagocytosis and Immune Regulation
- Cancer-related gene regulation
- CAR-T cell therapy research
- Immunodeficiency and Autoimmune Disorders
- CRISPR and Genetic Engineering
- Gut microbiota and health
- Immune cells in cancer
- Clostridium difficile and Clostridium perfringens research
- Diabetes and associated disorders
- Thyroid Disorders and Treatments
- Cytokine Signaling Pathways and Interactions
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
Molecular Oncology (United States)
2022-2024
University of Chicago
2010-2022
Hudson Institute
2017
Joslin Diabetes Center
2002-2010
Brigham and Women's Hospital
2002-2006
Carnegie Institution for Science
1999-2002
Department of Embryology
1999-2002
Harvard University
2002
Harvard University Press
2001
Carnegie Observatories
1999
Highlights•Inactivation of T cell autophagy results in enhanced tumor rejection•T cells deficient show increased glucose uptake and lactate production•Reduction SAM transcriptionally reprograms immune toward effector memorySummaryAutophagy is a survival process essential for the regulation responses to infections. However, role anti-tumor immunity less clear. Here, we demonstrate cell-autonomous CD8+ T-cell-mediated control tumors. Mice genes Atg5, Atg14, or Atg16L1 display dramatic...
Arthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs) directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase (GPI). To begin dissecting repertoire of arthritogenic immunoglobulins (Igs) model, and to provide basis for comparison with RA patientswe have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells lymphoid organs arthritic mice. cell clones specificities were present at extraordinarily high frequencies spleen,...
There is increasing appreciation of the important role B cells in many autoimmune diseases and consequently, interest treating these disorders through cell-depletion therapy with rituximab, an anti-CD20 monoclonal antibody. Yet, precisely how this related drugs exert their therapeutic effects remains controversial. In particular, it unclear how, a number contexts, rituximab can greatly reduce titer serum autoantibodies without substantially altering overall antibody titer. We have studied...
The RNA N6-methyladenosine (m6A) methylation is installed by the METTL3-METTL14 methyltransferase complex. This modification has critical regulatory roles in various biological processes. Here, we report that deletion of Mettl14 dramatically reduces mRNA m6A developing B cells and severely blocks cell development mice. Deletion impairs interleukin-7 (IL-7)-induced pro-B proliferation large-pre-B-to-small-pre-B transition causes dramatic abnormalities gene expression programs important for...
Significance In the thymus, developing T cells undergo negative selection to remove T-cell specificities that react self-antigens. This process generates a repertoire is tolerant one’s own tissues. It depends on antigen-presenting present self-antigens cells. paper characterizes development and function of poorly understood population B within thymus. These develop intrathymically, are phenotypically distinct from all other B-cell lineages, have properties make them extremely efficient at...
Background and aimsMouse models of colitis have been used to study the pathogenesis inflammatory bowel disease (IBD) for pre-clinical development therapeutic agents. Various epigenetic pathways shown play important regulatory roles in IBD. Reversible N6-methyladenosine (m6A) methylation represents a new layer post-transcriptional gene regulation that affects variety biological processes. We aim how deletion critical component m6A writer complex, METTL14, T cells colitis.MethodsConditional...
PD-1/PD-L1 blockade can promote robust tumor regression yet secondary resistance often occurs as immune selective pressure drives outgrowth of resistant clones. Here using a genome-wide CRISPR screen in B16.SIY melanoma cells, we confirm Ifngr2 and Jak1 important genes conferring sensitivity to T cell-mediated killing vitro. However, when implanted into mice, these Ifngr2- Jak1-deficient tumors paradoxically are better controlled immunologically. This phenotype maps defective PD-L1...
One of the genes that is up-regulated by thyroid hormone (TH) during Xenopus laevis metamorphosis encodes a type III deiodinase (D3) inactivates TH. Transgenic X. tadpoles overexpressing GFP-D3 fusion protein were produced. These transgenic had high levels activity and resistant to exogenous TH added 1 week after fertilization. They developed normally throughout embryogenesis premetamorphic stages but became retarded in their development late prometamorphosis when endogenous reaches its...
Metamorphosis of anuran tadpoles is controlled by thyroid hormone (TH). Here we demonstrate that transgenic Xenopus laevis expressing a dominant negative form TH receptor-α are resistant to wide variety the metamorphic changes induced TH. This result confirms receptors mediate both early and late developmental programs metamorphosis as diverse growth in brain, limb buds, nose Meckel's cartilage, remodeling intestine, death resorption gills tail.
The bacterial community that colonizes mucosal surfaces helps shape the development and function of immune system. K/BxN autoimmune arthritis model is dependent on microbiota, particularly segmented filamentous bacteria, for phenotype. mechanisms how gut microbiota affects are not well understood. In this study, we investigate contribution two T cell subsets, Th17 follicular helper (Tfh), to modulates their differentiation. Using genetic approaches, demonstrate IL-17 dispensable arthritis....
Two important features of amphibian metamorphosis are the sequential response tissues to different concentrations thyroid hormone (TH) and development negative feedback loop between pituitary gland that regulates TH synthesis by gland. At climax in Xenopus laevis (when level is highest), ratio circulating precursor thyroxine (T 4 ) active form 3,5,3′-triiodothyronine 3 blood many times higher than it tissues. This difference because conversion T target cells tadpole catalyzed enzyme type II...
Mice expressing the KRN T cell receptor transgene and MHC class II molecule A(g7) (K/BxN mice) develop severe inflammatory arthritis, serum from these mice causes similar arthritis in a wide range of mouse strains, owing to pathogenic autoantibodies glucose-6-phosphate isomerase (GPI). This model has been useful for investigation development autoimmunity transgenic particularly mechanisms by which anti-GPI induce joint-specific imflammation (serum transfer model). In this chaper, after...
Adult Xenopus laevis frogs made transgenic by restriction enzyme-mediated integration were bred to test the feasibility of establishing lines that express transgenes. All 19 animals raised sexual maturity generated progeny expressed transgene(s). The patterns and levels expression green fluorescent protein transgenes driven a viral promoter, rat four X. promoters all unaffected passage through germ line. These results demonstrate ease in .
Xenopus laevis tadpole tails contain fast muscle fibers oriented in chevrons and two pairs of slow “cords” along the length tail. When tail resorption is inhibited by a number different treatments, but not cord still lost, demonstrating that direct target thyroid hormone-induced death program. Expression dominant negative form hormone receptor (TRDNα) was restricted to means muscle-specific promoter. Even though transgene protects from (TH)-induced death, shortens, distal at tip are...
The antimalarial drug artemisinin and its derivatives exhibit potent immunosuppressive activity in several autoimmune disease models, however the mechanisms are not well-understood. This study was designed to investigate therapeutic effects underlying of analog artesunate using K/BxN mouse model rheumatoid arthritis. well-studied allowed us pinpoint effect on disease. Artesunate treatment prevented arthritis development young mice by inhibiting germinal center (GC) formation production...
N6-methyladenosine (m6A), the most common form of RNA modification, controls CD4+ T cell homeostasis by targeting IL-7/STAT5/SOCS signaling pathways. The role m6A modification in unconventional development remains unknown. Using mice with cell-specific deletion methyltransferase METTL14 (T-Mettl14−/−), we demonstrate that is indispensable for iNKT homeostasis. Loss METTL14-dependent leads to upregulation apoptosis double-positive thymocytes, which turn decreases Vα14-Jα18 gene...