Not listed EPIGENETIC REGULATION OF MAIT CELL DEVELOPMENT AND FUNCTION BY HISTONE DEMETHYLASE JMJD3 - PROJECT SUMMARY/ABSTRACT MUCOSAL-ASSOCIATED INVARIANT T (MAIT) CELLS ARE A SPECIALIZED SUBSET OF INNATE-LIKE T CELLS THAT RECOGNIZE MICROBIAL-DERIVED RIBOFLAVIN METABOLITES PRESENTED BY THE NON-POLYMORPHIC MHC CLASS I-RELATED MOLECULE MR1. MAIT CELLS ARE ENRICHED IN MUCOSAL TISSUES AND PLAY KEY ROLES IN ANTIMICROBIAL DEFENSE AND TISSUE HOMEOSTASIS. HOWEVER, THE TRANSCRIPTIONAL AND EPIGENETIC MECHANISMS GOVERNING MAIT CELL DEVELOPMENT AND FUNCTION REMAIN INCOMPLETELY DEFINED. RECENT DATA FROM OUR LABORATORY SUGGEST THAT THE HISTONE DEMETHYLASE JMJD3 (KDM6B), A KNOWN REGULATOR OF IMMUNE CELL DIFFERENTIATION, PLAYS A CRITICAL ROLE IN MAIT CELL BIOLOGY. USING A CONDITIONAL KNOCKOUT MODEL TARGETING JMJD3 IN DEVELOPING T CELLS, WE OBSERVED IMPAIRED MAIT CELL DEVELOPMENT AND FUNCTION, PARTICULARLY IN MAIT17, SUGGESTING THAT JMJD3 MAY REGULATE LINEAGE-DEFINING TRANSCRIPTIONAL PROGRAMS IN THESE CELLS. THIS PROJECT AIMS TO DEFINE THE ROLE OF JMJD3 IN MAIT CELL DEVELOPMENT AND EFFECTOR DIFFERENTIATION BY INTEGRATING FLOW CYTOMETRY, TRANSCRIPTOMIC, AND EPIGENOMIC APPROACHES IN BOTH WILD-TYPE AND JMJD3-DEFICIENT MICE. SPECIFIC GOALS INCLUDE: (1) DEFINING THE ROLE OF JMJD3 IN MAIT CELL HOMEOSTASIS, THYMIC EGRESS, AND FUNCTION; AND (2) DETERMINING THE MECHANISMS BY WHICH JMJD3 REGULATES MAIT CELL DEVELOPMENT AND FUNCTION. THESE STUDIES WILL CLARIFY HOW HISTONE DEMETHYLATION SHAPES MAIT CELL IDENTITY AND MAY REVEAL EPIGENETIC MECHANISMS THAT CAN BE THERAPEUTICALLY TARGETED IN MUCOSAL INFLAMMATORY DISEASES. THE PROPOSED FELLOWSHIP INCLUDES A COMPREHENSIVE TRAINING PLAN DESIGNED TO PROVIDE THE APPLICANT WITH EXPERTISE IN IMMUNOLOGY, EPIGENETICS, AND COMPUTATIONAL BIOLOGY. TRAINING ACTIVITIES INCLUDE HANDS-ON EXPERIENCE WITH ADVANCED FLOW CYTOMETRY, SINGLE-CELL AND BULK RNA-SEQUENCING, ATAC-SEQ, AND CUT & RUN AS WELL AS FORMAL COURSEWORK IN STATISTICAL ANALYSIS AND CHROMATIN BIOLOGY. THE APPLICANT WILL BE MENTORED BY DR. QING-SHENG MI, AN EXPERT IN INNATE-LIKE T CELLS, AND SUPPORTED BY A MULTIDISCIPLINARY TEAM OF COMMITTEE MEMBERS AND COLLABORATORS. THE RESEARCH WILL BE CONDUCTED AT MICHIGAN STATE UNIVERSITY'S DEPARTMENT OF MICROBIOLOGY, GENETICS, AND IMMUNOLOGY (MGI), AN INSTITUTION WITH ROBUST RESOURCES IN IMMUNOLOGY, GENOMICS, AND MOUSE MODELS. THIS INTEGRATED RESEARCH AND TRAINING PLAN WILL PREPARE THE APPLICANT FOR A SUCCESSFUL CAREER AS AN INDEPENDENT INVESTIGATOR IN IMMUNOLOGY AND EPIGENETICS. $0 5/26/26 Not listed EPIGENETIC REGULATION OF MAIT CELL DEVELOPMENT AND FUNCTION BY HISTONE DEMETHYLASE JMJD3 - PROJECT SUMMARY/ABSTRACT MUCOSAL-ASSOCIATED INVARIANT T (MAIT) CELLS ARE A SPECIALIZED SUBSET OF INNATE-LIKE T CELLS THAT RECOGNIZE MICROBIAL-DERIVED RIBOFLAVIN METABOLITES PRESENTED BY THE NON-POLYMORPHIC MHC CLASS I-RELATED MOLECULE MR1. MAIT CELLS ARE ENRICHED IN MUCOSAL TISSUES AND PLAY KEY ROLES IN ANTIMICROBIAL DEFENSE AND TISSUE HOMEOSTASIS. HOWEVER, THE TRANSCRIPTIONAL AND EPIGENETIC MECHANISMS GOVERNING MAIT CELL DEVELOPMENT AND FUNCTION REMAIN INCOMPLETELY DEFINED. RECENT DATA FROM OUR LABORATORY SUGGEST THAT THE HISTONE DEMETHYLASE JMJD3 (KDM6B), A KNOWN REGULATOR OF IMMUNE CELL DIFFERENTIATION, PLAYS A CRITICAL ROLE IN MAIT CELL BIOLOGY. USING A CONDITIONAL KNOCKOUT MODEL TARGETING JMJD3 IN DEVELOPING T CELLS, WE OBSERVED IMPAIRED MAIT CELL DEVELOPMENT AND FUNCTION, PARTICULARLY IN MAIT17, SUGGESTING THAT JMJD3 MAY REGULATE LINEAGE-DEFINING TRANSCRIPTIONAL PROGRAMS IN THESE CELLS. THIS PROJECT AIMS TO DEFINE THE ROLE OF JMJD3 IN MAIT CELL DEVELOPMENT AND EFFECTOR DIFFERENTIATION BY INTEGRATING FLOW CYTOMETRY, TRANSCRIPTOMIC, AND EPIGENOMIC APPROACHES IN BOTH WILD-TYPE AND JMJD3-DEFICIENT MICE. SPECIFIC GOALS INCLUDE: (1) DEFINING THE ROLE OF JMJD3 IN MAIT CELL HOMEOSTASIS, THYMIC EGRESS, AND FUNCTION; AND (2) DETERMINING THE MECHANISMS BY WHICH JMJD3 REGULATES MAIT CELL DEVELOPMENT AND FUNCTION. THESE STUDIES WILL CLARIFY HOW HISTONE DEMETHYLATION SHAPES MAIT CELL IDENTITY AND MAY REVEAL EPIGENETIC MECHANISMS THAT CAN BE THERAPEUTICALLY TARGETED IN MUCOSAL INFLAMMATORY DISEASES. THE PROPOSED FELLOWSHIP INCLUDES A COMPREHENSIVE TRAINING PLAN DESIGNED TO PROVIDE THE APPLICANT WITH EXPERTISE IN IMMUNOLOGY, EPIGENETICS, AND COMPUTATIONAL BIOLOGY. TRAINING ACTIVITIES INCLUDE HANDS-ON EXPERIENCE WITH ADVANCED FLOW CYTOMETRY, SINGLE-CELL AND BULK RNA-SEQUENCING, ATAC-SEQ, AND CUT & RUN AS WELL AS FORMAL COURSEWORK IN STATISTICAL ANALYSIS AND CHROMATIN BIOLOGY. THE APPLICANT WILL BE MENTORED BY DR. QING-SHENG MI, AN EXPERT IN INNATE-LIKE T CELLS, AND SUPPORTED BY A MULTIDISCIPLINARY TEAM OF COMMITTEE MEMBERS AND COLLABORATORS. THE RESEARCH WILL BE CONDUCTED AT MICHIGAN STATE UNIVERSITY'S DEPARTMENT OF MICROBIOLOGY, GENETICS, AND IMMUNOLOGY (MGI), AN INSTITUTION WITH ROBUST RESOURCES IN IMMUNOLOGY, GENOMICS, AND MOUSE MODELS. THIS INTEGRATED RESEARCH AND TRAINING PLAN WILL PREPARE THE APPLICANT FOR A SUCCESSFUL CAREER AS AN INDEPENDENT INVESTIGATOR IN IMMUNOLOGY AND EPIGENETICS. $49.6k 5/26/26 Not listed EPIGENETIC REGULATION OF MAIT CELL DEVELOPMENT AND FUNCTION BY HISTONE DEMETHYLASE JMJD3 - PROJECT SUMMARY/ABSTRACT MUCOSAL-ASSOCIATED INVARIANT T (MAIT) CELLS ARE A SPECIALIZED SUBSET OF INNATE-LIKE T CELLS THAT RECOGNIZE MICROBIAL-DERIVED RIBOFLAVIN METABOLITES PRESENTED BY THE NON-POLYMORPHIC MHC CLASS I-RELATED MOLECULE MR1. MAIT CELLS ARE ENRICHED IN MUCOSAL TISSUES AND PLAY KEY ROLES IN ANTIMICROBIAL DEFENSE AND TISSUE HOMEOSTASIS. HOWEVER, THE TRANSCRIPTIONAL AND EPIGENETIC MECHANISMS GOVERNING MAIT CELL DEVELOPMENT AND FUNCTION REMAIN INCOMPLETELY DEFINED. RECENT DATA FROM OUR LABORATORY SUGGEST THAT THE HISTONE DEMETHYLASE JMJD3 (KDM6B), A KNOWN REGULATOR OF IMMUNE CELL DIFFERENTIATION, PLAYS A CRITICAL ROLE IN MAIT CELL BIOLOGY. USING A CONDITIONAL KNOCKOUT MODEL TARGETING JMJD3 IN DEVELOPING T CELLS, WE OBSERVED IMPAIRED MAIT CELL DEVELOPMENT AND FUNCTION, PARTICULARLY IN MAIT17, SUGGESTING THAT JMJD3 MAY REGULATE LINEAGE-DEFINING TRANSCRIPTIONAL PROGRAMS IN THESE CELLS. THIS PROJECT AIMS TO DEFINE THE ROLE OF JMJD3 IN MAIT CELL DEVELOPMENT AND EFFECTOR DIFFERENTIATION BY INTEGRATING FLOW CYTOMETRY, TRANSCRIPTOMIC, AND EPIGENOMIC APPROACHES IN BOTH WILD-TYPE AND JMJD3-DEFICIENT MICE. SPECIFIC GOALS INCLUDE: (1) DEFINING THE ROLE OF JMJD3 IN MAIT CELL HOMEOSTASIS, THYMIC EGRESS, AND FUNCTION; AND (2) DETERMINING THE MECHANISMS BY WHICH JMJD3 REGULATES MAIT CELL DEVELOPMENT AND FUNCTION. THESE STUDIES WILL CLARIFY HOW HISTONE DEMETHYLATION SHAPES MAIT CELL IDENTITY AND MAY REVEAL EPIGENETIC MECHANISMS THAT CAN BE THERAPEUTICALLY TARGETED IN MUCOSAL INFLAMMATORY DISEASES. THE PROPOSED FELLOWSHIP INCLUDES A COMPREHENSIVE TRAINING PLAN DESIGNED TO PROVIDE THE APPLICANT WITH EXPERTISE IN IMMUNOLOGY, EPIGENETICS, AND COMPUTATIONAL BIOLOGY. TRAINING ACTIVITIES INCLUDE HANDS-ON EXPERIENCE WITH ADVANCED FLOW CYTOMETRY, SINGLE-CELL AND BULK RNA-SEQUENCING, ATAC-SEQ, AND CUT & RUN AS WELL AS FORMAL COURSEWORK IN STATISTICAL ANALYSIS AND CHROMATIN BIOLOGY. THE APPLICANT WILL BE MENTORED BY DR. QING-SHENG MI, AN EXPERT IN INNATE-LIKE T CELLS, AND SUPPORTED BY A MULTIDISCIPLINARY TEAM OF COMMITTEE MEMBERS AND COLLABORATORS. THE RESEARCH WILL BE CONDUCTED AT MICHIGAN STATE UNIVERSITY'S DEPARTMENT OF MICROBIOLOGY, GENETICS, AND IMMUNOLOGY (MGI), AN INSTITUTION WITH ROBUST RESOURCES IN IMMUNOLOGY, GENOMICS, AND MOUSE MODELS. THIS INTEGRATED RESEARCH AND TRAINING PLAN WILL PREPARE THE APPLICANT FOR A SUCCESSFUL CAREER AS AN INDEPENDENT INVESTIGATOR IN IMMUNOLOGY AND EPIGENETICS. $49.6k 5/26/26 Not listed EPIGENETIC REGULATION OF MAIT CELL DEVELOPMENT AND FUNCTION BY HISTONE DEMETHYLASE JMJD3 - PROJECT SUMMARY/ABSTRACT MUCOSAL-ASSOCIATED INVARIANT T (MAIT) CELLS ARE A SPECIALIZED SUBSET OF INNATE-LIKE T CELLS THAT RECOGNIZE MICROBIAL-DERIVED RIBOFLAVIN METABOLITES PRESENTED BY THE NON-POLYMORPHIC MHC CLASS I-RELATED MOLECULE MR1. MAIT CELLS ARE ENRICHED IN MUCOSAL TISSUES AND PLAY KEY ROLES IN ANTIMICROBIAL DEFENSE AND TISSUE HOMEOSTASIS. HOWEVER, THE TRANSCRIPTIONAL AND EPIGENETIC MECHANISMS GOVERNING MAIT CELL DEVELOPMENT AND FUNCTION REMAIN INCOMPLETELY DEFINED. RECENT DATA FROM OUR LABORATORY SUGGEST THAT THE HISTONE DEMETHYLASE JMJD3 (KDM6B), A KNOWN REGULATOR OF IMMUNE CELL DIFFERENTIATION, PLAYS A CRITICAL ROLE IN MAIT CELL BIOLOGY. USING A CONDITIONAL KNOCKOUT MODEL TARGETING JMJD3 IN DEVELOPING T CELLS, WE OBSERVED IMPAIRED MAIT CELL DEVELOPMENT AND FUNCTION, PARTICULARLY IN MAIT17, SUGGESTING THAT JMJD3 MAY REGULATE LINEAGE-DEFINING TRANSCRIPTIONAL PROGRAMS IN THESE CELLS. THIS PROJECT AIMS TO DEFINE THE ROLE OF JMJD3 IN MAIT CELL DEVELOPMENT AND EFFECTOR DIFFERENTIATION BY INTEGRATING FLOW CYTOMETRY, TRANSCRIPTOMIC, AND EPIGENOMIC APPROACHES IN BOTH WILD-TYPE AND JMJD3-DEFICIENT MICE. SPECIFIC GOALS INCLUDE: (1) DEFINING THE ROLE OF JMJD3 IN MAIT CELL HOMEOSTASIS, THYMIC EGRESS, AND FUNCTION; AND (2) DETERMINING THE MECHANISMS BY WHICH JMJD3 REGULATES MAIT CELL DEVELOPMENT AND FUNCTION. THESE STUDIES WILL CLARIFY HOW HISTONE DEMETHYLATION SHAPES MAIT CELL IDENTITY AND MAY REVEAL EPIGENETIC MECHANISMS THAT CAN BE THERAPEUTICALLY TARGETED IN MUCOSAL INFLAMMATORY DISEASES. THE PROPOSED FELLOWSHIP INCLUDES A COMPREHENSIVE TRAINING PLAN DESIGNED TO PROVIDE THE APPLICANT WITH EXPERTISE IN IMMUNOLOGY, EPIGENETICS, AND COMPUTATIONAL BIOLOGY. TRAINING ACTIVITIES INCLUDE HANDS-ON EXPERIENCE WITH ADVANCED FLOW CYTOMETRY, SINGLE-CELL AND BULK RNA-SEQUENCING, ATAC-SEQ, AND CUT & RUN AS WELL AS FORMAL COURSEWORK IN STATISTICAL ANALYSIS AND CHROMATIN BIOLOGY. THE APPLICANT WILL BE MENTORED BY DR. QING-SHENG MI, AN EXPERT IN INNATE-LIKE T CELLS, AND SUPPORTED BY A MULTIDISCIPLINARY TEAM OF COMMITTEE MEMBERS AND COLLABORATORS. THE RESEARCH WILL BE CONDUCTED AT MICHIGAN STATE UNIVERSITY'S DEPARTMENT OF MICROBIOLOGY, GENETICS, AND IMMUNOLOGY (MGI), AN INSTITUTION WITH ROBUST RESOURCES IN IMMUNOLOGY, GENOMICS, AND MOUSE MODELS. THIS INTEGRATED RESEARCH AND TRAINING PLAN WILL PREPARE THE APPLICANT FOR A SUCCESSFUL CAREER AS AN INDEPENDENT INVESTIGATOR IN IMMUNOLOGY AND EPIGENETICS. $0 5/26/26