A5017141484- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune cells in cancer
- Immune Response and Inflammation
- Immune responses and vaccinations
- Neuroinflammation and Neurodegeneration Mechanisms
- CAR-T cell therapy research
- Metabolomics and Mass Spectrometry Studies
- Cytomegalovirus and herpesvirus research
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- Advanced Chemical Sensor Technologies
- Ubiquitin and proteasome pathways
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Tryptophan and brain disorders
- Neurogenesis and neuroplasticity mechanisms
- Immunotherapy and Immune Responses
- Genetics and Neurodevelopmental Disorders
- IL-33, ST2, and ILC Pathways
- Analytical Chemistry and Chromatography
- Toxoplasma gondii Research Studies
- Isotope Analysis in Ecology
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
Salk Institute for Biological Studies
2023-2025
University of California, San Diego
2016-2023
La Jolla Institute for Immunology
2020
Intestinal barrier leakage constitutes a potential therapeutic target for many inflammatory diseases and represents disease progression marker during chronic viral infections. However, the causes of altered gut remain mostly unknown. Using murine infection with lymphocytic choriomeningitis virus, we demonstrate that, in contrast to an acute strain, persistent isolate leads long-term replication hematopoietic mesenchymal cells, but not epithelial cells (IECs), intestine. Viral persistence...
During a microbial infection, responding CD8+ T cells give rise to effector that provide acute host defense and memory sustained protection. An alternative outcome is exhaustion, state of cell dysfunction occurs in the context chronic infections cancer. Although it evident exhausted (TEX) are phenotypically molecularly distinct from cells, factors regulating earliest events differentiation process TEX remain incompletely understood. Here, we performed single-cell RNA-sequencing...
Suppression of CD8 and CD4 T cells is a hallmark in chronic viral infections, including hepatitis C HIV. While multiple pathways are known to inhibit cells, the host molecules that restrict cell responses less understood. Here, we used inducible cell-specific deletion gene encoding TGF-β receptor during lymphocytic choriomeningitis virus infection mice, determined signaling restricted proliferation terminal differentiation antiviral cells. also inhibited cytotoxic program includes granzymes...
Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding how infections pathogens that exhibit distinct capability spread persist differentially change microbiome, underlying mechanisms, relative contribution individual commensal species cell is still lacking. Here, we discovered mouse infection fast-spreading persistent (but not slow-spreading acute)...
Abstract Chronic infections drive a CD8 T cell program termed exhaustion, characterized by reduced effector functions. While cell-intrinsic mechanisms underlying exhaustion have been extensively studied, the impact of metabolic environment in which exhausted cells (Tex) operate remains less clear. Using untargeted metabolomics and murine lymphocytic choriomeningitis virus infection model we investigated systemic metabolite changes early late following acute versus chronic viral infections....
Correspondence We introduce a web-enabled small-molecule mass spectrometry (MS) search engine. To date, no tool can query all the public tandem MS data in metabolomics repositories, greatly limiting utility of these resources clinical, environmental and natural product applications. Therefore, we Ma ss S pectrometry earch T ool (MASST) ( https://proteosafe-extensions.ucsd.edu/masst/ ), that enables discovery molecular relationships among accessible (MS/MS).
Significance This study utilizes novel transgenic reporter mice to definitively evaluate T cells coexpressing two cell antigen receptors. These experiments demonstrate that lymphocytes naturally different receptors are significantly more abundant than previous estimates and these have a previously unappreciated role in physiologic immune responses.
CD4+ T lymphocytes are crucial for controlling a range of innate and adaptive immune effectors. For CD8+ cytotoxic lymphocyte (CTL) responses, cells can function as helpers (TH) to amplify magnitude functionality or regulatory (Treg) capable profound inhibition. It is unclear what determines differentiation these phenotypes whether pathogens provoke alternate programs. We find that, depending on the size initial dose, Listeria infection drives act TH induces rapid polyclonal conversion...
The CD8+ T cell response to the intracellular parasite Toxoplasma gondii varies dramatically between mouse strains, resulting in stark differences control of parasite. Protection BALB/c mice can be attributed an unusually strong and protective MHC-1 Ld-restricted directed against a peptide derived from antigen GRA6. Ld molecule has limited binding compared conventional MHC molecules such as Kb or Db, which correlates with polymorphisms associated "elite control" HIV humans. To investigate...
Astrocytes are glial cells of the central nervous system that modulate neuronal function. Here, we present glyoxal-fixed astrocyte nuclei transcriptomics (GFAT), a protocol for purification and transcriptomic analysis from cortex cerebellum adult aged fresh mouse brain. We describe steps tissue dissection, glyoxal fixation, homogenization, isolation, antibody staining, fluorescence-activated cell sorting, RT-qPCR or bulk RNA sequencing. GFAT does not require transgenic lines viral injection...
Fragile X syndrome (FXS) is a monogenic neurodevelopmental disorder with manifestations spanning molecular, neuroanatomical, and behavioral changes. Astrocytes contribute to FXS pathogenesis show hundreds of dysregulated genes proteins; targeting upstream pathways mediating astrocyte changes in could therefore be point intervention. To address this, we focused on the bone morphogenetic protein (BMP) pathway, which upregulated astrocytes. We generated conditional KO (cKO) Smad4 astrocytes...
Abstract The CD8+ T cell response to the intracellular parasite Toxoplasma gondii varies dramatically between mouse strains, resulting in differences control of parasite. Protection BALB/c mice can be attributed an unusually strong and protective MHC-1 L d -restricted directed against a peptide derived from antigen GRA6. molecule has limited binding compared conventional MHC molecules such as K b or D , which correlates with polymorphisms associated “elite control” HIV humans. To investigate...