A5001162489- Gut microbiota and health
- Immune Cell Function and Interaction
- Tryptophan and brain disorders
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Clostridium difficile and Clostridium perfringens research
- RNA Interference and Gene Delivery
- Dermatology and Skin Diseases
- Chronic Lymphocytic Leukemia Research
- Mycobacterium research and diagnosis
- MicroRNA in disease regulation
- Ginseng Biological Effects and Applications
- PARP inhibition in cancer therapy
- COVID-19 Impact on Reproduction
- SARS-CoV-2 and COVID-19 Research
- Dietary Effects on Health
- GABA and Rice Research
- RNA modifications and cancer
- Animal Virus Infections Studies
- Cytomegalovirus and herpesvirus research
- Gastrointestinal motility and disorders
- Cancer therapeutics and mechanisms
- Pharmacological Effects of Medicinal Plants
- Glycosylation and Glycoproteins Research
UConn Health
2020-2024
Jackson Laboratory
2018-2024
Washington University in St. Louis
2010-2014
Center of Molecular Immunology (Cuba)
2007-2009
Rockefeller University
2001-2008
Dendritic cells (DCs) have the capacity to initiate immune responses, but it has been postulated that they may also be involved in inducing peripheral tolerance. To examine function of DCs steady state we devised an antigen delivery system targeting these specialized presenting vivo using a monoclonal antibody DC-restricted endocytic receptor, DEC-205. Our experiments show this route is several orders magnitude more efficient than free peptide complete Freund's adjuvant (CFA) T cell...
A large number of miRNAs have recently been discovered in plants and animals. Development reverse genetic approaches that act to inhibit microRNA function would facilitate the study this new class noncoding RNA. Here we show 2′-O-methyl oligoribonucleotides, but not 2′-deoxyoligonucleotides specifically inactivate RNAi activity associated with miRNA–protein complexes human cell extracts as well cultured cells.
Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between host system, metabolism diet have not been studied over time this disorder.We performed six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting patients 25 age, sex, race matched healthy control individuals. Gut composition function were characterized using 16S metagenomic...
To understand the dynamic interplay between human microbiome and host during health disease, we analyzed microbial composition, temporal dynamics, associations with multi-omics, immune, clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that stability individuality are body-site specific heavily influenced by host. The stool oral more stable than skin nasal microbiomes, possibly due to their interaction environment. identify individual-specific...
The mycobiome is the fungal component of gut microbiome and implicated in several autoimmune diseases. However, its role MS has not been studied.In this case-control observational study, we performed ITS sequencing characterised people with (pwMS) healthy controls at baseline after six months.The had significantly higher alpha diversity inter-subject variation pwMS than controls. Saccharomyces Aspergillus were over-represented pwMS. was positively correlated circulating basophils negatively...
Chromosome translocations between oncogenes and the region spanning immunoglobulin (Ig) heavy chain (IgH) variable (V), diversity (D), joining (J) gene segments (Ig V-J(H) region) are found in several mature B cell lymphomas humans mice. The breakpoints frequently adjacent to recombination signal sequences targeted by activating genes 1 2 during antigen receptor assembly pre-B cells, suggesting that these might be result of aberrant V(D)J recombination. However, cells undergoing...
Lymphocyte antigen receptor gene assembly occurs through the process of V(D)J recombination, which is initiated when RAG endonuclease introduces DNA DSBs at two recombining segments to form broken coding end pairs and signal pairs. These paired ends are joined by proteins nonhomologous end-joining (NHEJ) pathway DSB repair a joint joint, respectively. generated in G1-phase developing lymphocytes, where they activate ataxia telangiectasia mutated (Atm) DNA-PKcs kinases orchestrate diverse...
The powerful immune responses elicited by the mRNA vaccines targeting SARS-CoV-2 Spike protein contribute to their high efficacy. Yet, efficacy can vary greatly between individuals. For not based on mRNA, cumulative evidence suggests that differences in composition of gut microbiome, which impact vaccine immunogenicity, are some factors variations However, it is unclear if microbiome impacts novel mode immunogenicity vaccines. We conducted a prospective longitudinal cohort study individuals...
Abstract Background Despite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. The development of novel therapeutic preventative approaches is highly desirable. Accumulating evidence in the past several years has established associations between gut microbiome microbial metabolites with behavior, but druggable targets their underlying mechanism action understudied. Results Here, using a drink-in-the-dark mouse model, we...
The humoral immune response critically relies on the secondary diversification of antibodies. This takes places through somatic remodelling antibody genes by two molecular mechanisms, Class Switch Recombination (CSR) and Somatic Hypermutation (SHM). enzyme Activation Induced Cytidine Deaminase (AID) initiates both SHM CSR deaminating cytosine residues DNA immunoglobulin genes. While crucial for immunity, AID-catalysed deamination is also triggering event generation lymphomagenic chromosome...
V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at border between two recombining gene segments, generating hairpin-sealed coding ends and blunt signal ends. ATM DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are serine-threonine kinases that orchestrate cellular responses to DSBs. During recombination, DNA-PKcs have unique functions in repair of deficiency leads instability postcleavage complexes loss from these...
Summary To understand dynamic interplay between the human microbiome and host during health disease, we analyzed microbial composition, temporal dynamics, associations with multi-omics, immune clinical markers of microbiomes from four body sites in 86 participants over six years. We found that stability individuality are body-site-specific heavily influenced by host. The stool oral were more stable than skin nasal microbiomes, possibly due to their interaction environment. Also, identified...
Chromosome translocations between Ig (Ig) and non-Ig genes are frequently associated with B-cell lymphomas in humans mice. The best characterized of these is c-myc/IgH translocation, which Burkitt's lymphoma. These caused by activation-induced cytidine deaminase (AID), produces double-strand DNA breaks both genes. rare events, part because ATM, p53, p19 actively suppress them. To further define the mechanism protection against accumulation cells that bear we assayed B from mice carry...
The resection of broken DNA ends is required for double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal nonhomologous end joining (NHEJ), the main DSB pathway in G1-phase cells. Antigen receptor gene assembly proceeds through intermediates generated lymphocytes RAG endonuclease. These DSBs activate ATM, which phosphorylates H2AX, forming γ-H2AX flanking chromatin. prevents CtIP from initiating DSBs. Whether there are additional proteins to promote these not...
Growing evidence has linked an altered host fecal microbiome composition with health status, common chronic diseases, and institutionalization in vulnerable older adults. However, fewer studies have described changes healthy adults without major confounding diseases or conditions, the impact of aging on across different body sites remains unknown. Using 16S ribosomal RNA gene sequencing, we reconstructed oral microbiomes young (23–32; mean = 25 years old) (69–94; 77 community-dwelling...