Gene Regulation in Innate Immunity

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Katherine A. Fitzgerald
Organization: UNIV OF MASSACHUSETTS MED SCH WORCESTER
Fiscal Year: 2024
Award: $490,775
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY (See instructions):
The goal of this project is to understand mechanisms of gene regulation in the innate immune response. 
During the past many years, with support from this grant, we have pioneered work with fundamental 
implications to our understanding of inflammatory responses. During the past 5 years, the funding stability 
provided by this MERIT award, enabled us to significantly expand our field of expertise, which resulted in 
several highly significant and unexpected discoveries, which form the basis of the work proposed over the 
next 5 years of the award. In particular, we documented a totally novel nucleic acid binding protein CNBP 
which directs Th1 immune response in vivo and connected lncRNA biology to innate immunity and the 
inflammatory process. In the proposed extension of this MERIT award we will advance on the foundational 
observations that linked Cnbp as a specific regulator of IL12p40 gene transcription by defining in detail the 
molecular mechanisms of Cnbp-dependent control of c-Rel. We will also explore the cell type specific role 
of Cnbp in controlling Th1 immunity using the T. gondii model. Further, we will explore the contribution of 
Cnbp in control of the IL23-TH17 response. Lastly, we will expand on our studies of lincRNA-Cox2 to 
explore regulation of Cox2 and immune responses in vivo.

Terms: <Animals><Antigenic Determinants><Award><Binding><Binding Determinants><Binding Proteins><Binding Sites><Biochemical><Biology><Breeding><C albicans><C. albicans><C.albicans><CD11c><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Candida albicans><Cas nuclease technology><Cell Body><Cell Lineage><Cell Nucleus><Cells><ChIP Sequencing><ChIP-seq><ChIPseq><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Combining Site><Complement><Complement Proteins><Complex><Confocal Microscopy><Cytosol><DNA><DNA Binding><DNA Binding Interaction><DNA bound><DSS colitis><DSS model><DSS mouse model><DSS-induced acute colitis><DSS-induced colitis><Deoxyribonucleic Acid><EMSA><Edodekin Alfa><Epitopes><Family><Functional RNA><Funding><Gene Action Regulation><Gene Expression><Gene Expression Regulation><Gene Family><Gene Regulation><Gene Regulation Process><Gene Transcription><Genes><Genetic Alteration><Genetic Change><Genetic Transcription><Genetic defect><Genome><Goals><Grant><Human><IL-12><IL-23><IL12><ITGAX><ITGAX gene><Immune><Immune response><Immunes><Immunity><Immunological response><Inflammatory><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Inflammatory Response><Innate Immune Response><Innate Immunity><Instruction><Interleukin-12><Interphase Cell><KO mice><Knock-out Mice><Knockout Mice><Ligand Binding Protein><Ligand Binding Protein Gene><Link><LoxP-flanked allele><Luciferase Immunologic><Luciferases><Macrophage><Maps><Mice><Mice Mammals><Modeling><Modern Man><Molecular><Molecular Interaction><Murine><Mus><Mutation><Myeloid Cells><Mφ><NKSF><Native Immunity><Natural Immunity><Natural Killer Cell Stimulatory Factor><Non-Coding><Non-Coding RNA><Non-Specific Immunity><Non-dividing Cell><Non-translated RNA><Noncoding RNA><Nondividing Cell><Nonspecific Immunity><Nontranslated RNA><Nuclear><Nuclear Translocation><Nucleic Acid Regulator Regions><Nucleic Acid Regulatory Sequences><Nucleus><Null Mouse><Phase><Process><Protein Binding><Proteins><RNA Expression><Reactive Site><Regulation><Regulatory Regions><Reporter Genes><Resting Cell><Role><Site><Specificity><T gondii><T. gondii><Testing><Toxoplasma gondii><Transcription><Untranslated RNA><Work><bound protein><cell type><chromatin immunoprecipitation-sequencing><colitis-induced dysbiosis><complementation><dextran sulfate sodium colitis><dextran sulfate sodium induced colitis><dextran sulfate sodium model><dextran sulfate sodium mouse model><experiment><experimental research><experimental study><experiments><floxed><floxed allele><genetic regulatory element><genome mutation><host response><immune system response><immunoresponse><in vivo><inflammatory disease of the intestine><inflammatory disorder of the intestine><insight><interleukin-23><intestinal autoinflammation><mutant><noncoding><novel><nucleic acid binding protein><promoter><promotor><response><social role>