NIH_SPENDING_CATS: Aging;Brain Disorders;Clinical Research;Genetics;Human Genome;Immunotherapy;Neurodegenerative;Neurosciences;Parkinson's Disease

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease and has been linked to movement abnormalities, rapid reduction of synaptic function, and sometimes memory impairment. This proposal will examine the role of T-lymphocytes in PD in the periphery at different disease phases, in the brain where synaptic loss occurs, and from a genetics perspective linking PD risk loci to T-cell-mediated disease mechanism. Understanding how T-cells impact PD is critical for understanding the pathogenesis of disease and informing future diagnostic and treatment efforts.

PI_NAMEs: ROSEN, MIKAELA  (contact)

PROJECT_TERMS: Adaptive Immune System;Age;Alleles;alpha synuclein;Antigen-Presenting Cells;Antigens;Autopsy;biological heterogeneity;Biological Markers;biomarker discovery;Blood;Blood specimen;Brain;brain parenchyma;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;Cellular biology;Cerebrospinal Fluid;Characteristics;Clinical;clinically relevant;Clonality;Clone Cells;cohort;comparison control;complementarity-determining region 3;Complex;Comprehension;computational pipelines;Data;Data Set;Development;Diagnosis;Diagnostic;Disease;Disease Progression;disorder risk;Disputes;dopaminergic neuron;Dyskinetic syndrome;experimental study;Future;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic association;Genetic Carriers;Genetic Recombination;Genetic Transcription;genome sequencing;genome wide association study;Genotype;Goals;Histocompatibility Antigens Class II;HLA Antigens;Human;Immune;immune function;Immune Targeting;Immunologic Markers;Immunotherapeutic agent;in silico;In Vitro;in vivo;Individual;Infiltration;Inflammatory;insight;Lead;Lewy Bodies;Link;LRRK2 gene;Major Histocompatibility Complex;Measures;Mediating;Memory impairment;Mentors;Methods;mouse model;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;new therapeutic target;novel marker;Outcome;Parkinson Disease;Pathogenesis;Pathology;Patients;Peptides;Peripheral;peripheral blood;Phase;Play;protective allele;Proteins;Quantitative Trait Loci;REM Sleep Behavior Disorder;Reporting;Resolution;response;Risk;Risk Factors;risk variant;Role;Sampling;Shapes;single cell sequencing;single-cell RNA sequencing;Specificity;Statistical Models;Substantia nigra structure;Synapses;synaptic function;T cell clonality;T cell infiltration;T-Cell Antigen Receptor Specificity;T-cell diversity;T-Cell Immunologic Specificity;T-Cell Receptor;T-Cell Receptor Genes;T-cell receptor repertoire;T-Lymphocyte;Technology;Therapeutic;therapeutic biomarker;Therapeutic Intervention;transcriptome;whole genome;Work

PROJECT_TITLE: Role of T-lymphocytes in Idiopathic and Genetic Parkinson's Disease


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: LOS ANGELES

ORG_COUNTRY: UNITED STATES

ORG_DEPT: CHEMISTRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE The fidelity of cell division is critical for the accurate alignment and segregation of chromosomes, but malfunctions in this process can introduce mitotic errors, contributing to uncontrolled growth and tumorigenesis. Protein phosphatases have recently emerged as promising targets for cancer treatment due to their ability to regulate critical signaling pathways involved in cell division. The proposed research will investigate the mechanistic functions of the newly identified phosphatase DUSP12 in cell division with the goal of advancing our understanding of human cell proliferation and facilitating the development of novel therapeutic interventions in proliferative disorders.

PI_NAMEs: ABDUSAMAD, MAI  (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Abnormal Cell;Address;Affect;Affinity;Apoptosis;Binding;Biochemical;Biological;Biological Assay;Biological Models;cancer cell;Cancer cell line;cancer therapy;Cell Cycle Progression;Cell Death;Cell Death Induction;Cell Death Process;Cell division;Cell Proliferation;Cell Survival;Cells;Cellular biology;Chromosome Segregation;Chromosomes;Complement;Complex;Coupled;daughter cell;design;Development;Disease;DNA Sequence Alteration;Ensure;Enzymes;Equilibrium;Event;experimental study;Flow Cytometry;Fluorescence Microscopy;follow-up;Foundations;Genetic;Genetic Materials;Genetic Screening;Goals;Growth;Health;Human;human disease;Imaging Techniques;In Vitro;insight;Link;liver ischemia;Malignant Neoplasms;MAPK1 gene;Mass Spectrum Analysis;Mediating;Mitosis;Mitotic;Modification;Molecular;Myocardial Reperfusion Injury;novel;novel therapeutic intervention;oxidative damage;Pathway interactions;Phosphoric Monoester Hydrolases;Phosphorylation;Physiological;Play;Ploidies;Process;Proliferating;Protein Dephosphorylation;Protein phosphatase;Proteins;Proteomics;Publishing;Regulation;Repression;Research;RNA interference screen;Role;segregation;Series;Signal Pathway;Specificity;Testing;tumor progression;tumorigenesis;uncontrolled cell growth;Work;Zinc;Zinc Fingers

PROJECT_TITLE: Defining the role of DUSP12 in the regulation of cell division and apoptosis.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-Q (20)]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Tuberculosis

ORG_CITY: SAINT LOUIS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Neutrophils are the predominantly infected cell in active tuberculosis patients; however, it is unknown why this innate immune cell is unable to kill Mycobacterium tuberculosis (Mtb). The type VII secretion system, ESX-1, is required for Mtb survival and growth in neutrophils but it is unclear what neutrophil function(s) are dysregulated due to this secretion system. This proposed research will uncover the neutrophil pathways affected by ESX-1 activity and how this activity promotes Mtb growth, providing critical insights into the mechanisms Mtb uses to reprogram the immune system during tuberculosis.

PI_NAMEs: RANKIN, ANANDA NICHOLE (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Affect;Anti-Bacterial Agents;antimicrobial;Bronchoalveolar Lavage Fluid;Cell Death;cell type;Cells;Communicable Diseases;Complement;Complex;Cytoplasmic Granules;Cytosol;Data;Development;Disease;DNA;ELF3 gene;experimental study;Exposure to;extracellular;Galactose Binding Lectin;Galectin 3;Growth;Histones;Human;Immune;Immune system;Immunocompetent;Individual;Infection;insight;Integration Host Factors;Interferon Type I;Interferon-beta;Kinetics;latent infection;Link;Lung;Macrophage;Measures;Methods;Monitor;mouse model;Mus;Mycobacterium tuberculosis;NADPH Oxidase;Nature;Necrosis;neutrophil;Neutrophil Infiltration;Nuclear;Outcome;pathogen;Pathogenesis;Pathway interactions;Patients;Permeability;Phagocytosis;Phagosomes;Phosphorylation;Population;Predisposition;Process;Production;programs;Protein-arginine deiminase;Reactive Oxygen Species;recruit;Research;Resected;response;Role;Signal Transduction;Site;Sputum;Stimulator of Interferon Genes;Structure of parenchyma of lung;System;Testing;trafficking;transcriptome sequencing;Tuberculosis;Vesicle;vesicle transport;World Health Organization

PROJECT_TITLE: Discovering how Mycobacterium tuberculosis promotes its survival in neutrophils

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07A-B (20)]


ORG_DEPT: BIOCHEMISTRY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE  With the rising prevalence of antibiotic-resistant infections, traditional antimicrobial approaches are facing increasing limitations, necessitating careful study of the factors underlying these infections and innovative strategies for their treatment. This study aims to investigate how bacteria can utilize reverse transcriptase enzymes to overcome their viral predators, bacteriophages, in the course of infecting their human hosts. The results of this investigation will illuminate how antiviral immune systems in bacteria contribute to their pathogenicity, and guide novel intervention strategies to combat antibiotic resistance.

PI_NAMEs: TANG, STEPHEN  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Active Sites;alternative treatment;Antibiotic Resistance;antibiotic resistant infections;Antibiotic Therapy;antimicrobial;Antimicrobial Resistance;Bacteria;Bacterial Model;Bacteriophages;Biochemical;Biological;Biological Assay;career;career development;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;college;combat;Communities;Complementary DNA;Dedications;Defense Mechanisms;design;Development;DNA biosynthesis;Doctor of Philosophy;effective intervention;Engineering;enteric infection;Enterobacteriaceae;Enzymes;experimental study;Fellowship;Future;Genes;Genetic;Genetic Screening;gut colonization;gut microbes;gut microbiome;Horizontal Gene Transfer;Human;Immune system;Immunity;Immunoprecipitation;In Vitro;in vivo;Infection;innovation;insight;Intervention;Intestines;Invaded;Investigation;Knowledge;Laboratories;Link;Mediating;Medical;microbiome;Modality;Modeling;Modification;Molecular;Morbidity - disease rate;mortality;Multi-Drug Resistance;Mutate;novel;novel strategies;Nucleic Acids;Organism;Pathogenesis;pathogenic bacteria;Pathogenicity;Pathway interactions;patient population;Physicians;Play;portability;Predatory Behavior;Prevalence;Prevention strategy;Process;programs;Proliferating;prophylactic;Public Health;reconstitution;Research Personnel;Resistance;resistance mechanism;Reverse Transcription;RNA;RNA Binding;RNA immunoprecipitation sequencing;RNA-Directed DNA Polymerase;Role;Scientist;Surgeon;System;Techniques;Training;Universities;Viral;virome;ward;Work

PROJECT_TITLE: Mechanisms of reverse transcriptase mediated phage resistance in Enterobacteriaceae


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: SEATTLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE  Enteric infections, specifically the resulting diarrheal disease, are a leading cause of morbidity and mortality for children under 5 years old in low-income settings. Drinking water contamination, a key source of exposure to enteric pathogens, can be influenced by various household water handling behaviors and seasonal variation in water resources. This project will investigate if and how household water handling practices impact enteric pathogen infection in 12-month-old children in Beira, Mozambique, and the effect of seasonality on these pathways, which will allow for a better understanding of the pathways through which drinking water impacts acute health outcomes.

PI_NAMEs: KANN, REBECCA SHIELDS (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: 5 year old;Acute;Address;Age Months;age related;Antigen-Antibody Complex;Behavior;Behavioral;Biological;Child;Child Health;Child Mortality;Chronic;Classification;Cohort Studies;Consumption;contaminated drinking water;Cryptosporidium;Data;Development;Diarrhea;diarrheal disease;Disease;disease transmission;drinking water;Dryness;Effectiveness;Enteral;enteric infection;enteric pathogen;Environmental Exposure;exposure pathway;exposure route;Exposure to;Floods;Growth;gut microbiome;Health;health assessment;Household;Immune response;Impact evaluation;improved;Income;Infant;Infection;Infrastructure;insight;Intervention;low and middle-income countries;Low income;Measures;Mediation;Mediator;Morbidity - disease rate;mortality;Mozambique;Outcome;pathogen;Pathogen detection;pathogenic Escherichia coli;Pathway interactions;Persons;Play;prospective;Public Health;Randomized, Controlled Trials;Reporting;Research;Resources;Role;Seasonal Variations;Seasons;Source;study population;Surveys;Symptoms;System;Testing;transmission process;urban setting;vaccine access;vaccine delivery;Vaccines;Water;water quality;Water Supply;water treatment;waterborne;waterborne illness

PROJECT_TITLE: Assessing the impact of water handling practices and seasonality on the effectiveness of a drinking water intervention in Beira, Mozambique


ADMINISTERING_IC: ES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: East Greenwich

ORG_NAME: GORDON RESEARCH CONFERENCES

ORG_STATE: RI

PHR: PROJECT SUMMARY Oxidation of the thiol (–SH) of select protein cysteines can act as a molecular switch to adapt protein function and modulate cellular signaling events in response to metabolic changes and stress conditions. Excessive levels of cellular oxidants as a consequence of genetic alterations, environmental exposure, inflammation, or aging can disrupt thiol-based redox signaling with a range of pathological consequences, including cardiovascular and lung disease, neurodegeneration, and many cancers. This conference brings together world class scientists from across the career spectrum to exchange the newest research and ideas centered on the spatial and temporal aspects of thiol-based redox signaling within and between cells, with the goal to advance our understanding of these events and to translate this knowledge into new diagnostic and therapeutic strategies.

PI_NAMEs: SEVIER, CAROLYN S (contact)

PROGRAM_OFFICER_NAME: RAVICHANDRAN, LINGAMANAIDU V

PROJECT_TERMS: Acute;age-related disease;Aging;aging related;Alkylation;Animal Model;Area;Attention;Bioinformatics;Biological;Biological Markers;Biological Models;Biology;biophysical techniques;cancer cell;Cardiovascular Diseases;career;Cell model;Cells;Cessation of life;Chemicals;Chemistry;Chronic Disease;Clinical;Collaborations;Communication;Communities;Cysteine;design;Detection;diagnostic development;Discipline;Disease;doctoral student;Education;Environment;Environmental Exposure;Event;experience;Faculty;Functional disorder;Future;gene environment interaction;Global Change;Goals;graduate student;Hazardous Substances;Homeostasis;Human;human disease;Individual;Inflammation;Knowledge;Life;Link;Lung Diseases;Malignant Neoplasms;medical specialties;meetings;Mentors;Mentorship;Metabolic;Methods;Mission;Modification;Molecular;multiple omics;Mutation;National Institute of Environmental Health Sciences;Nerve Degeneration;Nitrogen;novel;novel diagnostics;novel therapeutic intervention;Organelles;Organism;Outcome;Oxidants;oxidation;Oxidation-Reduction;Oxygen;Participant;Pathologic;Pathology;Physicians;Physiological Processes;Physiology;Play;Post-Translational Protein Processing;Postdoctoral Fellow;posters;Prevention;Process;professional atmosphere;programs;protein function;Proteins;recruit;Recurrence;Regulation;Relaxation;Request for Proposals;Research;Research Personnel;response;Role;Running;Scientist;Signal Transduction;Societies;Sorting;Source;Spain;Stimulus;Stress;student participation;Students;success;Sulfhydryl Compounds;Sulfur;supportive environment;symposium;Talents;Therapeutic;Toxic effect;Toxicology;Translating;United States National Institutes of Health

PROJECT_TITLE: 2024 Thiol-Based Redox Regulation and Signaling Gordon Research Conference and Gordon Research Seminar

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 BWD-W (R3)]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: GAINESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative The stagnant therapeutic development in peripheral arterial disease (PAD) and lack of success of angiogenic therapies warrants further investigation of non-vascular cells contribution to limb functionality. Experiments outlined in this predoctoral fellowship seek to understand how the accumulation of intramuscular adipose tissue (IMAT), an understudied hallmark of severe PAD, contributes to ischemic limb function using genetic and pharmacological approaches in preclinical models. This fellowship will provide thorough technical and intellectual training to a promising young scientist in several areas including stem cell, muscle, and vascular biology.

PI_NAMEs: PALZKILL, VICTORIA R (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Adipocytes;Adipose tissue;Adult;Affect;Agonist;Amputation;Angiogenic Factor;antagonist;Area;Atherosclerosis;Biology;Blood capillaries;Blood flow;blood vessel occlusion;Blood Vessels;candidate identification;Cardiovascular system;career;Cell Communication;Cell Nucleus;cell type;Cells;Chronic;chronic ulcer;Cilostazol;Clinical;Clinical Trials;clinically relevant;Complex;Data;Deposition;Development;Disease;Duchenne muscular dystrophy;Equilibrium;Evaluation;experimental study;Failure;Fellowship;femoral artery;Fibrosis;Foundations;Functional disorder;Future;gain of function;Gangrene;Genes;Genetic;genetic manipulation;Goals;Grant;Growth;high risk;Histologic;Homeostasis;Hypoxia;improved;In Situ;Infiltration;intercellular communication;Intervention;Intramuscular;Investigation;Ischemia;ischemic injury;Isolated limb perfusion;Lasers;Leg;Ligation;limb amputation;limb ischemia;Limb structure;Link;lipid biosynthesis;loss of function;Lower Extremity;Manuscripts;Measures;Mediating;Medical;Mentors;Mentorship;Mesenchymal Stem Cells;Modeling;Molecular;Molecular Biology;Molecular Genetics;mortality;mortality risk;multiple omics;Multipotent Stem Cells;Mus;Muscle;Muscle function;Muscular Atrophy;Myofibroblast;Nerve;normoxia;novel;novel therapeutics;Operative Surgical Procedures;Outcome Measure;Pain;Pathologic;Pathology;Patients;Perfusion;Peripheral arterial disease;pharmacologic;Physiology;Play;Population;Pre-Clinical Model;pre-doctoral;primary outcome;progenitor;Proteins;Proteomics;Recovery;Research;Resolution;Rest;revascularization surgery;Role;Scientist;Signal Pathway;Signal Transduction;Signaling Molecule;Skeletal Muscle;skills;stem cell biology;stem cell differentiation;stem cells;success;Symptoms;Technology;Testing;Therapeutic;therapeutic development;therapeutic target;Therapeutic Trials;Time;Tissues;Training;Training Programs;transcriptome;transcriptome sequencing;transcriptomics;United States;Vascular regeneration;Writing

PROJECT_TITLE: Molecular Mechanisms of Intramuscular Adipose Tissue in Chronic Limb Threating Ischemia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-D (20)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Neurosciences;Substance Misuse

ORG_DEPT: PSYCHOLOGY

PHR: PROJECT NARRATIVE  The objective of this F32 is to assess the psychological experience of chronic stress and dynamic functional connectivity within the brain’s stress coping network in a clinical sample with alcohol use disorder (AUD) and matched controls. To advance the translational impact of the science of the stress neurocircuitry in AUD, this proposal will integrate psychological and neural levels of analysis to elucidate the relationship between chronic stress and temporal variability within brain’s stress coping network AUD versus matched controls.

PI_NAMEs: KIRSCH, DYLAN E (contact)

PROGRAM_OFFICER_NAME: HAGMAN, BRETT THOMAS

PROJECT_TERMS: acute stress;Alcohol consumption;alcohol testing;alcohol use disorder;Alcohols;Brain;Brain Diseases;career development;Chronic;chronic alcohol ingestion;Chronic stress;Clinical;clinical diagnosis;Clinical Research;clinical training;coping;Data Collection;Decision Making;Development;Event;Exhibits;experience;flexibility;Fostering;Functional impairment;Functional Magnetic Resonance Imaging;Goals;Grant;Health;Human;Individual;interest;Interview;Life;Life Stress;Literature;Measures;Methodology;Methods;Modeling;Mood Disorders;National Research Service Awards;Nature;neural;neural circuit;neuromechanism;Neurosciences;Occupational;Outcome;Outcome Measure;parent grant;Participant;Patient Self-Report;pre-clinical;preclinical study;Prefrontal Cortex;primary outcome;psychologic;Questionnaires;recruit;Regression Analysis;Relapse;Reporting;Research Personnel;resilience;Resources;Rest;Role;Sampling;Science;Signal Transduction;skill acquisition;skills;Slide;Stress;Stress and Coping;stress resilience;Structure;System;Testing;Time;Training;Training Activity;Translating;translational impact;Work

PROJECT_TITLE: A clinical neuroscience approach to understand stress coping in alcohol use disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZAA1 GG (32)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: HERSHEY

ORG_DEPT: NEUROSURGERY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: PROJECT NARRATIVE Parkinson’s disease (PD) patients suffer from elevated levels of brain iron with levodopa (L-DOPA) commonly used by clinicians as a first-line antiparkinson drug. This project will research how our standard administration of L-DOPA impacts critical properties of iron homeostasis with the goal of identifying key iron mechanisms in the blood-brain barrier which will be confirmed by utilizing an in-vitro blood-brain barrier model and in-vivo murine model. This research will allow for the understanding of the mechanism of iron transport after L-DOPA exposure and target critical regulators to reduce brain iron accumulation and improve antiparkinson drug therapy development.

PI_NAMEs: SERPA, REBECKA OLIVEIRA (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Address;Adult;Affect;Anemia;Animal Model;Animals;Antiparkinson Agents;Astrocytes;Attenuated;Binding;Biology;Blood - brain barrier anatomy;blood-brain barrier permeabilization;Brain;brain iron;career;cerebral microvasculature;Clinical;Collaborations;Communication;Competence;Complement;Complex;cytotoxic;Data;Development;Diagnosis;Diet;Disease Management;Disease Progression;Dopa;Dopamine;Dopaminergic Agents;dopaminergic neuron;Drug Exposure;Endothelial Cells;Evaluation;experience;experimental study;Fellowship;Female;Foundations;FTH1 gene;Goals;H ferritin;High Prevalence;Histologic;Homeostasis;Hour;Human;human induced pluripotent stem cells;Image;improved;In Vitro;in vivo;Incubated;Inflammation;inhibitor;Iron;iron deficiency;iron metabolism;Iron Overload;iron supplement;Iron-Regulatory Proteins;Knowledge;Learning;Levodopa;Long-Evans Rats;Magnetic Resonance Imaging;male;Manuscripts;Measures;Metabolic;Metabolism;Microglia;Midbrain structure;Modeling;Molecular;Monoamine Oxidase B;motor deficit;mouse model;Nerve Degeneration;Neurodegenerative Disorders;Neurosciences;new therapeutic target;novel;Oral;Parkinson Disease;Patients;Pharmaceutical Preparations;Pharmacotherapy;Pre-Clinical Model;progressive neurodegeneration;Property;prospective;Proteins;Rattus;Regulation;Reporting;Research;Research Personnel;Research Project Grants;reuptake;Risk Factors;Role;Scientist;Selegiline;Severities;side effect;Signal Transduction;slow potential;Solid;Stains;standard care;standard of care;Substantia nigra structure;Symptoms;System;Techniques;Testing;therapeutic target;therapy development;Time;Training;Transferrin;translational applications;Translational Research;translational study;Treatment Efficacy;uptake;Western Blotting

PROJECT_TITLE: Contribution of Levodopa to Brain Iron Accumulation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03C-K (20)]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: BALTIMORE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Despite the improved short-term outcomes in kidney transplantation (KT), comparable progress in long-term allograft survival has not been achieved with chronic allograft injury (CAI) accounting for most of the cases of graft loss. Results of our planned studies will identify early molecular pathways predating eventual graft repair or deterioration which will allow for the exploration of new therapeutic targets that have the potential to prevent irreversible kidney damage. Novel prognostic biomarkers will enable the early identification of patients at higher risk for progression to CAI, allowing for the development of new therapeutic modalities that have the potential to avoid irreversible graft injury and improve long-term outcomes.

PI_NAMEs: ARCHER, KELLIE J.;MAS, VALERIA RAQUEL (contact)

PROGRAM_OFFICER_NAME: ABBOTT, KEVIN C

PROJECT_TERMS: Accounting;Acute Renal Failure with Renal Papillary Necrosis;aged;Allografting;Atrophic;Biopsy;Categories;Cell Communication;Cell Lineage;Cell Nucleus;Cell Physiology;cell type;Cells;Cessation of life;Characteristics;Chromatin;Chronic;Clinical;Complex;cost effective;Cytometry;Data;Deterioration;Development;Diagnosis;Early identification;Epithelial Cells;epithelial injury;Evaluation;Event;Fibroblasts;Fibrosis;Funding;Gene Expression;Gene Expression Profile;Genes;Genetic Markers;genetic signature;genomic data;graft dysfunction;graft failure;graft function;Graft Survival;high dimensionality;high risk;Histologic;Image;Immune;Immune response;immunoregulation;Impairment;improved;Infiltration;Inflammation;Inflammatory;Inflammatory Response;injured;Injury;injury and repair;interstitial;isoimmunity;Kidney;kidney biopsy;kidney cell;Kidney Diseases;Kidney Transplantation;Lead;Macrophage;Maps;Measurable;Measures;Modality;Modeling;Molecular;Molecular Profiling;Monitor;monocyte;Myofibroblast;new therapeutic target;novel;novel therapeutics;Nucleic Acid Regulatory Sequences;Organ;Outcome;Pathway interactions;Patients;Peripheral;Peripheral Blood Mononuclear Cell;Play;predictive marker;predictive signature;preimplantation;prevent;Prognostic Marker;programs;progression risk;Publications;recruit;renal damage;Renal function;repaired;Resources;response to injury;Risk;risk stratification;Role;Sampling;Shapes;single nucleus RNA-sequencing;single-cell RNA sequencing;Statistical Methods;Statistical Models;stem-like cell;Time;time use;Tissue Donors;tissue repair;transcriptome;transcriptome sequencing;Transitional Cell;Transplant Recipients;Transplantation;Transposase;Tubular formation;Validation;wound

PROJECT_TITLE: Assessment of Donor Quality for Improving Kidney Transplant Outcomes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-W (05)]


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Immunization;Infectious Diseases;Inflammatory Bowel Disease;Microbiome

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative A subset of commensal microbial antigens is trafficked to the thymus in early life and presented to developing thymocytes to expand microbiota-specific T cells. This proposal seeks to identify the microbial and immunological signals that promote microbe trafficking to the thymus during this developmental ‘window of opportunity’ and provide insight into the establishment of the commensal-reactive T cell repertoire. As microbe-specific T cells are implicated in protection against enteric infections, and the pathology underlying Inflammatory Bowel Disease, this project will advance our understanding of how the microbiome influences the development of the mucosal immune system.

PI_NAMEs: MATTHEWS, DEAN  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: 16S ribosomal RNA sequencing;absorption;Acute;Adherence;Adult;Affect;Antibodies;antibody transfer;Antigen-Antibody Complex;Antigen-Presenting Cells;Antigens;Autologous;B-Lymphocytes;Bacteria;Bacterial Adhesins;Bacterial DNA;beneficial microorganism;Clone Cells;Colitis;commensal bacteria;commensal microbes;critical period;Cues;Data;Dendritic Cells;Development;Digestion;Disease;Education;Elements;enteric infection;enteric pathogen;Environment;Epithelium;Escherichia;Escherichia coli;Escherichia coli Adhesins;experimental study;Fc Receptor;Feces;Feedback;Generations;gut microbes;gut microbiome;host-microbe interactions;Hypersensitivity;IgG Deficiency;IgG Receptors;Immune response;Immune signaling;Immune system;Immunity;Immunoglobulin G;Immunologic Memory;in utero;in vivo;Infection;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;insight;Instruction;Integration Host Factors;intestinal barrier;intestinal epithelium;Intestines;Invaded;lens;Life;Maternal antibody;Mediating;member;Microbe;microbial;microbial colonization;microbial signature;microbiome;microbiota;microorganism antigen;microorganism interaction;Milk;Modeling;Mothers;mouse model;Mucosal Immune System;Mucous Membrane;Mus;Neonatal;neonatal Fc receptor;neonate;novel therapeutics;offspring;pathogen;Pathogenesis;Pathogenicity;Pathology;Peptides;Peripheral;Population;Prevention;Process;Publications;pup;receptor;receptor expression;Regulation;Regulatory T-Lymphocyte;response;Role;Sampling;Shapes;Signal Transduction;Site;Symbiosis;T-Lymphocyte;Thymic Tissue;thymocyte;Thymus Gland;Tissues;trafficking;transcytosis;Vertical Transmission;Weaning;Work

PROJECT_TITLE: Regulation of Microbial Trafficking to the Thymus in Early Life


ADMINISTERING_IC: HD

IC_NAME: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric

ORG_CITY: ATLANTA

ORG_DEPT: BIOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE It is well known that genetics play an important role during development, and genetic mutations can lead to neurodevelopmental disorders (NDDs). It is not well understood how coding and non-coding mutations in certain genes cause a wide range of phenotypes seen in NDDs. A better understanding of how mutations in these genes affect gene expression and chromatin accessibility during neuronal development will provide further insight into the causes of NDDs.

PI_NAMEs: LOSKOVE, YONINA  (contact)

PROGRAM_OFFICER_NAME: OREILLY, JULIA JIAQI

PROJECT_TERMS: 3-Dimensional;Address;Affect;autism spectrum disorder;Behavioral;Bioinformatics;Biological Assay;brain dysfunction;brain tissue;candidate identification;candidate validation;Case/Control Studies;causal variant;Cell Nucleus;cell type;Cells;Cerebrum;Child;Chromatin;chromatin remodeling;Chromatin Remodeling Factor;Code;Coffin-Siris Syndrome;Cognitive;cohort;Collaborations;Complex;Data;Data Set;de novo mutation;Defect;Development;Developmental Delay Disorders;Diagnosis;Disease;DNA Sequence Alteration;Embryo;Embryonic Development;Enhancers;Etiology;Exhibits;Functional disorder;Gene Expression;Gene Expression Regulation;gene network;gene regulatory network;Genes;Genetic;Genetic Transcription;Genome;genome sequencing;Genomics;Harvest;Heritability;Human;human induced pluripotent stem cells;Individual;insight;Intellectual functioning disability;Knowledge;Lead;Link;Location;Molecular;Morphology;Motor;multiple omics;Mus;mutant;Mutate;Mutation;Neuroanatomy;Neurodevelopmental Disorder;neuron development;Neurons;Organoids;Other Genetics;Pathogenesis;Pathogenicity;Patients;Pattern;Phenotype;Play;Prevalence;Regulatory Element;Reporter;Research;Role;skills;Small Nuclear RNA;SMARCA4 gene;social;Specificity;Speech;Testing;Transcriptional Activation;Transfection;Translations;United States;Untranslated RNA;whole genome;Work

PROJECT_TITLE: Revealing the Defects in Gene Regulation that Link ARID1B to a Spectrum of Neurodevelopmental Disorders

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F08-L (20)]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Dementia;Infectious Diseases;Neurodegenerative;Neurosciences;Prevention;Sexually Transmitted Infections

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: This Project Summary/Abstract was originally submitted with R01 AG073193 and is included here unchanged to satisfy submission system requirements. PROJECT NARRATIVE Alzheimer's disease affects 1 in 9 Americans over 65 years of age, is the 6th leading cause of death, and costs $355 billion annually. Herein, we aim to understand how viruses interact with an aging olfactory system to accelerate Alzheimer's disease. This proposal will identify potential biomarkers and therapies (e.g. vaccines and antiviral agents) that may slow or halt progression to clinical dementia, disability, and death.

PI_NAMEs: NAGEL, MARIA ACENA;RESTREPO, DIEGO  (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Acceleration;Administrative Supplement;Affect;Age Years;Aging;Alzheimer's Disease;Alzheimer's disease pathology;American;Amyloid;Amyloid deposition;Anosmia;Anti-viral Agents;Behavioral;Biological;Cause of Death;Cells;Cessation of life;Clinical;comparison control;cost;Coupled;Data;Dementia;dementia risk;Deposition;disability;Disease;disease phenotype;Disease Progression;Endoscopy;entorhinal cortex;familial Alzheimer disease;Frequencies;Genes;Genetic Transcription;Herpesvirus 1;Herpesvirus Type 3;Hippocampus;Human;human old age (65+);Impaired cognition;Individual;Infection;Inflammatory;Liquid substance;Literature;Mus;Nasal cavity;Nerve Degeneration;neuroinflammation;Neuronal Differentiation;Neuronal Dysfunction;Nose;olfactory bulb;Olfactory dysfunction;Olfactory Epithelium;Olfactory Pathways;olfactory sensory neurons;Olfactory tract;optogenetics;overexpression;Pathologic Processes;Pathology;Pathway interactions;Peptides;potential biomarker;prevent;Production;Proteins;Risk Factors;Serum;Smell Perception;System;Testing;treatment risk;Up-Regulation;Vaccines;varicella-zoster virus immediate early protein 62;Viral;Virus

PROJECT_TITLE: Endoscopy for nasal amyloid deposits, Administrative Supplement under Virus and olfactory system interactions accelerate Alzheimer's disease pathology


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Bioengineering;Biomedical Imaging;Clinical Research;Disability Research;Machine Learning and Artificial Intelligence;Prevention;Rehabilitation

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Arthritis has affected numerous patients and caused long-term disabilities and morbidities. Joint instability precedes the onset of symptoms, i.e., when these progressive degenerative diseases are most treatable, but is oftentimes undetectable through the existing diagnostic imaging tests. This work will provide a novel CT imaging tool that will provide new anatomical and functional information on dynamic joint pathologies and facilitate early diagnosis of joint instability.

PI_NAMEs: GONG, HAO ;LENG, SHUAI  (contact)

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: 3-Dimensional;accurate diagnosis;Address;Adult;Affect;Anatomy;Anxiety;Arthritis;arthropathies;Arthroscopy;Attention;base;Biomechanics;bone;bone imaging;Bone structure;Bone Tissue;bone visualization;Cadaver;Carpometacarpal joint structure;Cartilage;cartilage degradation;Clinical;clinically significant;Code;Collagen;Color;Connective Tissue;Cost Savings;Custom;Data;data library;deep learning;Degenerative Disorder;density;Detection;Development;Diagnosis;Diagnostic Imaging;diagnostic tool;disabling symptom;Disease;Distal;Early Diagnosis;Early Intervention;experience;Fluoroscopy;four-dimensional computed tomography;functional disability;Functional impairment;Future;Goals;Hand;Health;Health Care Costs;heart motion;Image;imaging capabilities;Imaging Device;imaging modality;Imaging Techniques;improved;innovation;Intervention;joint function;joint injury;Joint Instability;Joints;kinematics;Lead;Learning;Ligaments;Logistic Regressions;Long term disability;Magnetic Resonance Imaging;Mental Depression;Methods;Morbidity - disease rate;Morphologic artifacts;Motion;MRI Scans;Neural Network Simulation;novel;novel diagnostics;Operative Surgical Procedures;Pain;Pathology;Patient Care;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phase;Physics;Procedures;productivity loss;Prospective cohort;Prospective Studies;radiological imaging;Reader;Reporting;Risk;Scanning;societal costs;soft tissue;Source;Specimen;Symptoms;synergism;Techniques;temporal measurement;Tendon structure;Testing;Thick;three-dimensional visualization;Thumb structure;Time;Training;ultrasound;Upper Extremity;vector;virtual;Visualization;Work;X-Ray Computed Tomography

PROJECT_TITLE: One-stop-shop Early Diagnosis of Joint Instability using AI-assisted 6D Computed Tomography

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ISB-N (03)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project narrative FOXP1 is important for early brain development and has been linked to a number of neurodevelopmental disorders. Here, I will discover the function of FOXP1 in the developing brain at a cell type level using genomic approaches. I will receive training in both experimental and computational methods and apply this knowledge to advance my career and make contributions to understanding brain development and disease.

PI_NAMEs: VOLLMER, RACHAEL  (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Affect;Animals;autism spectrum disorder;Behavioral;Biological Models;Brain;Bromodeoxyuridine;Candidate Disease Gene;candidate identification;career;cell cortex;Cell Proliferation;cell type;Cells;Child;Cleavage Under Targets and Release Using Nuclease;Collection;Communication impairment;Computing Methodologies;Corpus striatum structure;Data;Date of birth;Defect;Development;Disease;Embryo;Embryonic Development;Exhibits;experience;experimental study;Failure;Fiber;Foundations;FOXP1 gene;Gene Expression;Gene Expression Regulation;Gene Mutation;Gene Targeting;gene therapy;Genes;Genetic;Genomic approach;gliogenesis;Harvest;Hyperactivity;Individual;Injections;insight;Intellectual functioning disability;Knock-out;Knockout Mice;Knowledge;Language Disorders;Learning;Link;Methods;migration;model of autism spectrum disorder;Molecular;Morphology;mouse model;Mus;Mutation;Nature;Neocortex;neocortical;nerve stem cell;neurodevelopment;Neurodevelopmental Disorder;neurogenesis;Neuronal Differentiation;Neurons;Patients;Pattern;Phase;Phenotype;pregnant;premature;Process;Production;Proliferating;Prosencephalon;Radial;Regulation;Research;Resolution;risk variant;Role;Short-Term Memory;single nucleus RNA-sequencing;social deficits;spatial memory;Specific qualifier value;Stains;Structure;Syndrome;Technology;Testing;therapeutic target;Time;timeline;Tissues;Training;transcription factor;transcriptomics;Ultrasonics;Variant;vocalization

PROJECT_TITLE: Cell type-specific regulation of cortical development by the autism risk gene Foxp1

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03A-E (20)]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE Mitochondrial dysfunction is implicated in many human disease processes, including late stage liver failure. We have created a new animal model that deletes a gene critical for mitochondrial energy production. With this model, we will investigate the importance of mitochondrially derived energy in physiologic liver processes.

PI_NAMEs: MENEZES, CAMERON JOSEPH (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Ablation;Adult;Affect;Alleles;Animal Model;Animals;ATP Synthesis Pathway;Biological Assay;Biology;Body System;Body Weight decreased;Cachexia;Cell Cycle;Cell Physiology;conditional knockout;Coupled;Cultured Cells;Defect;Dependence;DNA biosynthesis;Electron Microscopy;Electron Transport;Electrophoresis;Exhibits;fatty liver disease;Functional disorder;Genes;Gluconeogenesis;Hepatic;Hepatocyte;Homeostasis;Human;human disease;Hypoproteinemia;Impairment;In Vitro;in vivo;insight;Investigation;Isotopes;Knock-out;Liver;Liver diseases;Liver Failure;liver function;liver injury;Liver Regeneration;Mass Spectrum Analysis;Measures;Membrane Potentials;Metabolic;metabolomics;Mitochondria;mitochondrial dysfunction;Modeling;Monitor;mouse model;Mus;Natural regeneration;next generation sequencing;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;Nuclear Magnetic Resonance;oligomycin sensitivity-conferring protein;Oligomycins;Organism;Oxidative Phosphorylation;Pathology;Patients;pharmacologic;Physiological;Physiology;Ploidies;Population;Process;Production;Protein Biosynthesis;Respiration;respiratory;ribosome profiling;Role;Route;Seminal;Severities;Specificity;Structure;success;Techniques;Testing;Tissues;tool;Transfer RNA;Transmission Electron Microscopy;wasting;Yeasts

PROJECT_TITLE: The role of mitochondrial ATP production in liver failure

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Fellowships in Digestive Diseases and Nutrition[DDK-F]


NIH_SPENDING_CATS: Bioengineering;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative Utilizing advances in human interactome structural characterization and covalent inhibitor development against reactive cysteines, this project proposes Artificial Intelligence methods to identify hyperreactive cysteines on protein-protein interaction (PPI) interfaces and explore covalent targeting of these cysteines with electrophilic molecules. The insights gained will open new possibilities for developing covalent inhibitors to modulate PPIs and potentially treat various human diseases.

PI_NAMEs: DURHAM, JESSE  (contact)

PROJECT_TERMS: 3-Dimensional;Active Sites;activity-based protein profiling;Address;Affinity;Affinity Chromatography;Artificial Intelligence;artificial intelligence method;Benchmarking;Binding;Binding Sites;Biological Assay;Biological Process;Cell Physiology;Charge;chemical fingerprinting;chemical property;Chemicals;cofactor;Communicable Diseases;Complex;Computer software;convolutional neural network;covalent bond;Cysteine;Data;Data Set;Databases;deep learning;design;Development;Disease;Docking;drug candidate;Drug Design;drug discovery;Drug Modulation;Drug Targeting;drug testing;Environment;Fingerprint;Future;Genetic Diseases;Human;human disease;human interactome;human model;improved;in silico;inhibitor;insight;Isotopes;kinase inhibitor;large datasets;Libraries;Ligands;Marketing;Mass Spectrum Analysis;Membrane Proteins;Methods;Modeling;Neural Network Simulation;novel therapeutics;Outcome;Pathologic;Pathway interactions;Pharmaceutical Preparations;Phosphotransferases;Play;Property;Protein Databases;Protein Inhibition;protein protein interaction;protein structure;Proteins;Proteolysis;Proteome;public database;Radar;Research;Resources;Role;screening;Set protein;Signal Pathway;Site;small molecule;small molecule inhibitor;Solid;Solvents;Structure;Surface;Testing;three dimensional structure;three-dimensional modeling;tool;Training;training data;Validation;virtual;virtual experiments;virtual screening

PROJECT_TITLE: Targeting hyper-reactive cysteines within PPI interfaces

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04-S (20)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences

ORG_CITY: SAN ANTONIO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: PROJECT NARRATIVE Alzheimer’s disease and related tauopathies currently have no cure or robust treatment plan. Understanding the molecular mechanisms driving neurodegeneration are vital for increasing our ability to accurately diagnose and treat patients suffering from neurodegenerative disorders. The proposed study will investigate basic mechanisms regulating mechanotransduction in neurons and will test the hypothesis that pathogenic tau drives neuronal death by disrupting neuronal nuclear mechanotransduction.

PI_NAMEs: SOHN, CLAIRA ROSE (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: accurate diagnosis;Actins;Affect;Aging;Alzheimer's Disease;Architecture;Automobile Driving;Binding;Biological Models;Brain;brain volume;Bulla;cell behavior;cell immortalization;Cell Nucleus;Cell Physiology;Cell Proliferation;cell type;Cells;Cerebrovascular system;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;cranium;Cytoplasm;Cytoskeleton;Deposition;Disease;emerin;Environment;Exposure to;Extracellular Matrix;Foundations;Frontotemporal Dementia;Gene Expression;Genes;Goals;Health;Heterochromatin;Human;Induced pluripotent stem cell derived neurons;Lamin Type A;Lamin Type B;Lamins;Literature;Location;mechanical force;mechanical signal;Mechanical Stimulation;mechanical stimulus;Mechanical Stress;Mechanics;mechanotransduction;Mediating;Microscopy;Mitotic;Molecular;Mutation;Neoplasm Metastasis;Nerve Degeneration;Neurobiology;neuroblastoma cell;Neurodegenerative Disorders;Neuroglia;neuron loss;Neurons;novel;Nuclear;Nuclear Envelope;Nuclear Inner Membrane;Nuclear Pleomorphism;Pathogenicity;Pathologic;Patients;Phosphorylation;Phosphorylation Site;Physiological;Process;Property;Proteins;Reporting;Research;response;Role;skills;superresolution microscopy;tau dysfunction;tau expression;tau mutation;tau Proteins;Tauopathies;Testing;Toxic effect;Training;treatment planning;Tyrosine;Visualization;Work

PROJECT_TITLE: Investigating mechanisms of neuronal nuclear mechanotransduction in physiological conditions and tauopathy


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Microbiome;Nutrition;Obesity

PHR: PROJECT NARRATIVE Recent years have seen the development of the concept that gut microbes provide a wealth of bioactive small molecules toward the host, and that these small molecules can consequentially influence diverse physiological processes. Our research group demonstrated that supplementation of mice fed a high fat and high sugar diet (Western-style diet) with a novel beneficial microbe, namely Lactococcus lactis subsp. cremoris (LLC) lowers total cholesterol, decreases hepatic adiposity, and lowers the levels of pro-inflammatory cytokines in the liver, but the mechanisms whereby this beneficial effect occur is unknown. We will identify LLC-induced shifts in the metabolome of mice fed a Western style diet and identify the therapeutic targets of LLC mediated cytoprotection in the liver.

PI_NAMEs: GACASAN, CAMILO ANTHONY G (contact)

PROJECT_TERMS: absorption;acetaminophen-induced liver injury;Amino Acids;Bacteria;beneficial microorganism;Biological Response Modifier Therapy;Biology;bioprocess;Cardiovascular Diseases;career;Cholesterol;Choline Deficiency;Circulation;clinically relevant;Computer Analysis;Computer software;Cytochrome P450;cytokine;Cytoprotection;Data;Data Set;Development;Diet;Disease;Energy Metabolism;Epidemiology;experimental study;Fatty acid glycerol esters;fatty acid metabolism;Fatty Liver;fatty liver disease;Fundulus heteroclitus;Gastroenterologist;gastrointestinal epithelium;germ free condition;Germ-Free;Gnotobiotic;Goals;graduate school;gut microbes;gut microbiota;Health;Hepatic;Histologic;Homeostasis;Human;improved outcome;Inflammation;Inflammatory;insight;Insulin Resistance;Intestinal Diseases;Laboratory Finding;Lactococcus lactis;Lipids;Lipopolysaccharides;Liver;Liver diseases;liver injury;Mass Spectrum Analysis;Mediating;Metabolic;Metabolic Pathway;Metabolic syndrome;Metabolism;metabolome;metabolomics;Methodology;Microbe;microbial;microbial products;microbiome;microbiota;Modality;Modeling;Molecular;Mus;next generation;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;novel therapeutics;Obesity;obesogenic;Pathway interactions;Patient-Focused Outcomes;phenylacetic acid;Physicians;Physiological Processes;Portal vein structure;Process;Prokaryotic Cells;Publishing;Research;response;Role;Saline;Scientist;Shapes;Signal Pathway;Signal Transduction;small molecule;Stimulus;sugar;Supplementation;Testing;therapeutic target;Tissues;Training;western diet;Xenobiotics

PROJECT_TITLE: Beneficial microbe driven rewiring of metabolic pathways in the gut and liver


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Brain Disorders;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Fragile X syndrome (FXS) is the most common cause of autism due to an epigenetic silencing of the X-linked FMR1 gene. In this project I propose to study the developmental deficits of FXS in 3D cortical organoids derived from patient induced pluripotent stem cells. This project should uncover the role of FMRP in neuronal differentiation and maturation throughout cortical development and uncover novel molecular mechanisms to be used for the development of FXS treatments.

PI_NAMEs: SANDOVAL, SORAYA OROZCO (contact)

PROJECT_TERMS: 3-Dimensional;Affect;Aggressive behavior;Animal Model;Anxiety;autism spectrum disorder;beta Spectrin;Brain;Calcium;Cell Line;Cell Proliferation;cell type;Cells;chromatin remodeling;Clinical Trials;Data;Defect;Development;Diagnosis;differential expression;Dorsal;Drosophila genus;Drug Screening;Electroencephalography;epigenetic silencing;Exhibits;Female;fetal;Fragile X Syndrome;Gene Expression;Genes;genetic signature;Genetic study;Human;human induced pluripotent stem cells;Hyperactivity;Image;Immunohistochemistry;Individual;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Inherited;Intellectual functioning disability;Knock-out;Label;language impairment;Link;male;Measures;Mendelian disorder;messenger ribonucleoprotein;Mitochondria;Modeling;Molecular;Morphology;mRNA Stability;multi-electrode arrays;Mus;nerve stem cell;neurodevelopment;Neurodevelopmental Disorder;neuron development;Neuronal Differentiation;Neurons;neuropathology;neuropsychiatric disorder;novel;Organoids;Oxidative Stress;Pathway interactions;patient derived induced pluripotent stem cells;patient stratification;Patients;Pharmaceutical Preparations;Pharmacotherapy;Play;postsynaptic;presynaptic;Prosencephalon;Proteins;Rest;RNA Transport;RNA-Binding Proteins;Rodent Model;Role;single nucleus RNA-sequencing;Symptoms;Synapses;synaptogenesis;Testing;therapeutic development;Time;tool;transcriptome sequencing;Translations;Transplantation;Up-Regulation;women's diagnosis;Work

PROJECT_TITLE: Characterization of Fragile X Syndrome 3D Cortical Organoids


NIH_SPENDING_CATS: Anxiety Disorders;Biotechnology;Brain Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Neurosciences;Post-Traumatic Stress Disorder (PTSD);Precision Medicine;Prevention

ORG_CITY: BELMONT

ORG_NAME: MCLEAN HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE In the United States, approximately 8% of the civilian and up to 30% of the active military and veteran population will experience post-traumatic stress disorder (PTSD), and, in the absence of diagnostic biomarkers and targeted therapeutic interventions, the costs of PTSD are staggering. We will study the genomic architecture of PTSD, with a focus on (i) gene expression, DNA methylation and protein expression of whole brain regions, (ii) gene expression and epigenetics in individual brain cells, and (iii) SNP-specific CRIPSR-editing of iPSC derived cul- tures exposed to glucocorticoids. Finally, we will characterize phenotypes associated with identified variants and networks to better understand how molecular mechanisms underlying PTSD are linked to specific symptoms, to improve PTSD prevention and treatment long-term.

PI_NAMEs: DASKALAKIS, NIKOLAOS  (contact);NIEVERGELT, CAROLINE M;RESSLER, KERRY J.

PROGRAM_OFFICER_NAME: PRICE, AMANDA JOY

PROJECT_TERMS: 17q21;Amygdaloid structure;Architecture;Autopsy;Behavioral;Biological;Biological Markers;Brain;brain based;brain cell;Brain region;brain tissue;causal variant;Cell Nucleus;cell type;Clinical;clinically relevant;clinically significant;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Cognitive;cost;Data;Data Collection;Databases;Development;diagnostic biomarker;diagnostic development;differential expression;DNA Methylation;Electronic Health Record;Environment;Epigenetic Process;epigenomics;Evaluation;experience;Exposure to;follow-up;Functional disorder;Future;Gene Expression;gene network;gene regulatory network;Gene set enrichment analysis;Genes;Genetic Markers;Genetic Risk;Genetic Transcription;genome wide association study;genome-wide;Genomics;Glucocorticoids;Heritability;Hippocampus;improved;In Vitro;Individual;Individual Differences;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Intervention;Link;Maps;Meta-Analysis;Methods;Military Personnel;military veteran;Molecular;molecular phenotype;Multiomic Data;multiple omics;Network-based;neural;Neurobiology;Neuroglia;neuroimaging;neuromechanism;Neurons;novel;Pathway interactions;Performance;personalized therapeutic;phenome;phenomics;Phenotype;polygenic risk score;Post-Traumatic Stress Disorders;Predisposition;Prefrontal Cortex;Prevention;protein expression;Proteomics;psychiatric genomics;Research;response;Risk;risk prediction;risk variant;Role;Sampling;severe mental illness;sex;Signal Pathway;single nucleus RNA-sequencing;Stress;Symptoms;targeted treatment;Testing;Therapeutic Intervention;Tissues;transcriptome;transcriptomics;Translating;Trauma;United States;Untranslated RNA;Variant

PROJECT_TITLE: Next steps for PTSD genomics: from loci to function

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Dental, Oral, and Craniofacial Disease;Pediatric;Prevention

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: PROJECT NARRATIVE This project addresses the limitations in current parenting assessments by introducing innovative approaches and advanced psychometric methods. The objectives include revising the Multidimensional Assessment of Parenting Scale (MAPS) through qualitative interviews and text mining analyses, developing and cross- validating revised MAPS versions for self-report (MAPS-S), coparent-report (MAPS-C), and youth-report (MAPS-Y), and developing optimal ecological momentary assessment (EMA) versions of the MAPS for parent- coparent and parent-youth dyads. Capitalizing on ethnoracially diverse national samples including fathers and piloting Spanish measures will further ensure the scales’ robustness and generalizability, thereby advancing parenting research and interventions aimed at improving youth health outcomes.

PI_NAMEs: RODRIGUEZ, VIOLETA DE JESUS (contact)

PROGRAM_OFFICER_NAME: MILLER, BECKY

PROJECT_TERMS: Abbreviations;Acceleration;Achievement;Address;advanced analytics;Agreement;career;career development;Child Rearing;Classification;Clinical;clinical care;cognitive interview;Communication;Comprehension;cost;Data;Development;Dimensions;diversity and inclusion;doctoral student;Ecological momentary assessment;Educational process of instructing;Ensure;Equation;ethnoracial;ethnoracial minority;Exhibits;experience;Family;Fathers;field study;Funding;Goals;Guidelines;Head;Health;Health behavior;HRK gene;Illinois;improved;indexing;informant;innovation;Institution;Intervention;intervention program;Interview;Lead;Leadership;Manuscripts;Maternal Health;Measurement;Measures;meetings;Mentorship;Methods;Modeling;Monitor;novel;novel strategies;Outcome;parenting intervention;Parents;Patient Self-Report;Peer Review;Play;prevent;Prevention program;professor;Property;Psychology;Psychometrics;Publications;Qualitative Methods;Recording of previous events;Reporter;Reporting;Research;research in practice;Research Personnel;Research Proposals;response;Role;Sampling;Schedule;Scientist;Secure;sex;Spanish;Statistical Models;Structure;student mentoring;Students;supportive environment;Surveys;systematic review;Teacher Professional Development;tenure track;Testing;text searching;theories;Training;Trees;United States National Institutes of Health;Universities;Validation;Vision;Youth

PROJECT_TITLE: Optimizing the Assessment of Parenting: A Multi-Method and Multi-Informant Approach

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 HSS-E (70)]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Biotechnology;Immunotherapy;Microbiome

ORG_CITY: IRVINE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE  The ability of human gut microbes to produce bioactive metabolites may provide a conserved signaling pathway for host-microbial communication. Microbial carbohydrate-active enzymes (CAZymes) are an exciting target for altering host-accessible glycan metabolites, which have been shown to be translationally relevant in a number of immune-active states including inflammatory diseases and certain cancers. Deciphering host- microbial dynamics through the chemoproteomic discovery of highly functional CAZymes could lead to the development of novel, engineered probiotics to selectively control glycan metabolite output in human host systems.

PI_NAMEs: FALCO, NATALIE  (contact)

PROJECT_TERMS: Acids;activity-based protein profiling;Affect;Alkynes;Animals;Antibiotics;Bacteria;Bifidobacterium;Biological Assay;Biology;Biotin;Cancer Model;Carbohydrates;career;career development;Cell Differentiation process;Cell Wall;Chemicals;chemoproteomics;Circulation;Communication;Development;Disease;Distant;Engineered Probiotics;Engineering;Enzymes;Event;Fellowship;Future;gain of function;Genetic Engineering;genomic data;Genomics;Germ-Free;Goals;gut colonization;gut microbes;gut microbiota;Harvest;Health;host-microbe interactions;Human;Hydrolase;Hydrolysis;Immune;Immune checkpoint inhibitor;Immune response;Immunity;Immunologics;Immunomodulators;Immunotherapy;improved;in vivo;Individual;Infection;Inflammatory;Insulin;Knowledge;Label;Lead;Letters;Malignant Neoplasms;Mass Spectrum Analysis;Measures;Mentors;Metabolic;Metabolism;Methods;Microbe;microbial;microbial host;microbiota;Mitochondria;mouse model;multiple reaction monitoring;Mus;novel;Organism;Output;Peptide Hydrolases;Peptidoglycan;Phylogenetic Analysis;Polysaccharides;Positioning Attribute;Postdoctoral Fellow;Probability;Probiotics;Production;Protein Secretion;Proteomics;Reaction;Research;Research Personnel;Saccharomyces;Scientist;Serum;Signal Pathway;skills;System;Therapeutic;tool;Training;Work;Writing

PROJECT_TITLE: Chemoproteomic discovery of secreted microbial enzymes for engineered probiotics


NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative The proposed studies aim to elucidate the chemical logic of neuromodulation by determining the implications of co-expression of receptors in primary neurons and intact brain tissue. This proposal utilizes the latest tools in transcriptomics, genetics, and live microscopy to better understand the diversity of cell types and neuron communication. The cellular understanding of neuromodulation gained will have important translational ramifications as neuromodulation is key to unlocking the brain in healthy and diseased states.

PI_NAMEs: HE, XINYI JENNY (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TITLE: Mapping the functional GPCR-ome and its signaling consequences in neurons

STUDY_SECTION_NAME: Special Emphasis Panel[ZMH1 ERB-P (02)]


NIH_SPENDING_CATS: Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences

PHR: PROJECT NARRATIVE  Hippocampal long-term synaptic potentiation (LTP) is critical to learning and memory. The execution of LTP requires activity-dependent transcription, but how a dysregulation of that contributes to intellectual disability remains elusive. Supported by our preliminary data, we will study the mechanisms by which tumor suppressor p53 mediates long-term synaptic potentiation and how defective expression of p53 and p53-dependent transcription contributes to intellectual disability.

PI_NAMEs: TSAI, NIEN-PEI  (contact)

PROGRAM_OFFICER_NAME: LEE, CRYSTAL ANNE

PROJECT_TERMS: Acids;Apoptosis;Behavior;Cell Cycle;Cell Physiology;Cells;Chemicals;Chemosensitization;Communication;conditional knockout;Data;Defect;Electrophysiology (science);Environment;excitatory neuron;FMR1 gene;Gene Expression;Genetic;Genetic Transcription;Goals;Hippocampus;imaging modality;Impairment;improved;in vivo;Intellectual functioning disability;knock-down;Knockout Mice;Knowledge;learned behavior;Learning;Long-Term Potentiation;Mediating;Memory;Mental disorders;Modeling;Molecular;mouse model;Mus;N-Methyl-D-Aspartate Receptors;Nervous System;Nervous System Disorder;Neuronal Differentiation;Neurons;novel;Organism;Pathway interactions;pharmacologic;postsynaptic;presynaptic;Process;Prosencephalon;protein expression;PTEN gene;receptor;Research;Role;Surface;Synapses;Synaptic plasticity;Synaptic Transmission;Testing;TP53 gene;transcription factor;Translations;Up-Regulation;Work

PROJECT_TITLE: The tumor suppressor p53 in hippocampal plasticity and intellectual disability

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Women's Health Research

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: PROJECT NARRATIVE  Harmful DNA breaks caused by exposure to radiation, chemicals, or as a result of mistakes that occur when DNA is being duplicated are usually repaired accurately through a process called homologous recombination (HR). When a DNA break occurs in an HR-deficient cell, it triggers a highly error-prone, cancer- inducing backup DNA repair pathway called microhomology-mediated end joining (MMEJ), and cells produce large amounts of the protein that performs MMEJ: DNA polymerase theta (PolQ). My project will uncover the step-by-step mechanism of how PolQ performs MMEJ and inform new strategies for discovering molecules that inhibit PolQ function to be investigated as potential HR-deficient cancer drugs.

PI_NAMEs: ZERIO, CHRISTOPHER JOHN (contact)

PROGRAM_OFFICER_NAME: ELJANNE, MARIAM

PROJECT_TERMS: Address;Amino Acids;Antineoplastic Agents;ATP phosphohydrolase;Binding;Biochemical;Biological;Biological Assay;BRCA1 gene;C-terminal;cancer cell;carcinogenesis;Cell model;Cells;Characteristics;Chemicals;Chromosome abnormality;cofactor;combat;computerized data processing;CRISPR/Cas technology;Cryoelectron Microscopy;Data;Data Collection;Development;dimer;Disease;DNA;DNA annealing;DNA Binding;DNA Damage;DNA Double Strand Break;DNA Integration;DNA Repair;DNA Repair Pathway;DNA-Directed DNA Polymerase;ds-DNA;Elements;Environment;Exhibits;Exposure to;Foundations;Genes;Genomic Instability;Goals;helicase;homologous recombination;homologous recombination deficiency;Human;improved;Incubated;inhibitor;innovation;insight;intermolecular interaction;Learning;Length;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant neoplasm of pancreas;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Methodology;Molecular;Molecular Conformation;Mutagenesis;mutant;Mutate;Mutation;Myopathy;nanoluciferase;Nonhomologous DNA End Joining;novel;novel strategies;Pathway interactions;Physiological;Point Mutation;Polymerase;Postdoctoral Fellow;Preparation;Process;Proteins;Protomer;Radiation;recruit;repaired;Reporter;Role;Rotation;Sampling;Single-Stranded DNA;small molecule;Solid;structural biology;Structure;targeted treatment;Techniques;Testing;Therapeutic;therapeutic development;therapeutic target;Visualization;Work

PROJECT_TITLE: Elucidation of the Mechanism of Microhomology-Mediated End Joining by DNA Polymerase Theta


NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Infectious Diseases;Inflammatory Bowel Disease

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative CMV colitis is an increasing problem in clinical practice, especially in individuals who are immunosuppressed through treatment for Inflammatory Bowel Disease, cancer, or organ transplant. This project aims to understand the effect of CMV infection/reactivation on the colonic epithelium. These foundational studies of the epithelium are fundamental to identifying mechanisms of CMV colitis.

PI_NAMEs: GOODRUM, FELICIA D;PAEK, ANDREW LUTHER;THORNE, CURTIS ANDREW;WILSON, JEAN M (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Adherent Culture;Affect;Age;Antigens;Area;Benign;Biological Assay;Biology;Cancer Patient;cancer transplantation;Cell Death;cell type;Cells;Cessation of life;Characteristics;chemotherapy;Chronic;clinical practice;Colectomy;Colitis;Colon;Complex;Cytomegalovirus;Cytomegalovirus Colitis;Cytomegalovirus Infections;Cytoplasm;Data;Defect;Development;Disease;Endothelial Cells;Epithelial Cells;Epithelium;Extravasation;Eye;Failure;Fibroblasts;Gastrointestinal tract structure;Goals;healing;Hematogenous Spread;Human;Immune;immune function;Immunocompromised Host;immunosuppressed;Immunosuppression;Immunosuppressive Agents;Individual;Infection;Inflammation;Inflammatory Bowel Diseases;insight;Intercellular Junctions;intestinal barrier;intestinal epithelium;Intracellular Membranes;Investigation;latent infection;Link;Membrane;Molecular;monolayer;Morphology;mortality;Mucous Membrane;mutant;Nuclear;Organ Transplantation;Organoids;Pathway interactions;Patients;Pattern;permissiveness;Population;Primary Infection;Proliferating;Proteins;Race;reactivation from latency;Reporter;Resources;Shock;Signal Pathway;Signal Transduction;stem cells;Strigiformes;System;Testing;therapeutic target;Tight Junctions;Tissues;trafficking;Transcription Coactivator;Transplant Recipients;United States;Virus;Virus Shedding;Work

PROJECT_TITLE: Modulation of colonocyte barrier function and signaling by cytomegalovirus infection

STUDY_SECTION: DNPD

STUDY_SECTION_NAME: Digestive and Nutrient Physiology and Diseases Study Section [DNPD]


ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The interaction between MCL1 and the rBH3 motif positions MCL1 as a bridge between apoptotic signaling and other cellular homeostasis pathways. The proposed project will elucidate how MCL1 interacts with rBH3 motifs, and elucidating how MCL1 may modify bound protein structure and therefore function will lead to new insights in rBH3 function. Specifically, this proposal will elucidate how MCL1 interacts with the glycolytic enzyme hexokinase 2 to lead in an increase in the rate of glucose catalysis.

PI_NAMEs: MCGRIFF, ANNA K (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Active Sites;Address;Affect;Amino Acid Motifs;Apical;Apoptosis;Apoptotic;BCL2 gene;Binding;Binding Proteins;Biological Assay;Biological Models;Biology;Catalysis;CDK6-associated protein p18;Cell Cycle Progression;cell growth;cell growth regulation;Cell Physiology;Cells;Complement;Complex;Cryoelectron Microscopy;Crystal Formation;Data;Data Analyses;Data Collection;design;Disparate;Environment;Enzymes;Future;Generations;Glucose;Goals;hexokinase;Hexokinase 2;Homeostasis;Homologous Gene;Hydrophobicity;innovation;insight;Institution;interest;Knowledge;Lead;Learning;Malignant Neoplasms;Mammals;MCL1 gene;Metabolic;Metabolism;Methionine;Methodology;Methods;Modeling;Molecular;Molecular Conformation;mutant;Mutation;Nature;NMR Spectroscopy;novel;Nuclear Magnetic Resonance;Pathway interactions;Peptides;permissiveness;pharmacophore;Positioning Attribute;prevent;pro-apoptotic protein;Process;Protein Family;protein protein interaction;protein purification;protein structure;Proteins;Regulation;Research;Research Personnel;RNA;Role;Signal Transduction;skills;Structural Biologist;structural biology;structural determinants;Structure;Techniques;Time;Training;Transcriptional Regulation;Work;X-Ray Crystallography

PROJECT_TITLE: Structurally Defining rBH3 Interactions


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Gene Therapy;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Rare Diseases;Rett Syndrome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Women's Health Research

ORG_CITY: MAYWOOD

ORG_NAME: LOYOLA UNIVERSITY CHICAGO

PHR: PROJECT NARRATIVE Decreased MeCP2 signaling has been proposed as pathogenic across a broad range of neurological diseases and cancers; however, pharmaceutical and genetic targeting of MeCP2 is challenging because even a modest increase in expression over normal levels results in toxicity. Here we describe a strategy to prevent the binding of negative regulators of MeCP2 expression as a means to fine-tune MeCP2 dosage in increments that plateau at sub-toxic levels. Using the neurodevelopmental disease Rett syndrome as an example, we will demonstrate how this novel approach is a potentially safe and effective mechanism to treat MeCP2-associated disorders.

PI_NAMEs: VANDERPLOW, AMANDA  (contact)

PROJECT_TERMS: 3' Untranslated Regions;advanced disease;Adverse effects;Affect;Antisense Oligonucleotides;Area;Belief;Binding;Binding Sites;Biological Assay;Brain;Candidate Disease Gene;career;career development;Cell Line;Cells;Cementation;Chemicals;Complement;curative treatments;Data;derepression;design;Development;disabled;Disease;disease model;dosage;Dose;experience;experimental study;Female;Fibroblasts;Foundations;Gene Expression;Gene Expression Profile;gene replacement;gene therapy;Genes;Genetic;Goals;Human;in vivo;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Intervention;Link;locked nucleic acid;loss of function;loss of function mutation;malignant neurologic neoplasms;MeCP2 Duplication Syndrome;Mentors;Messenger RNA;Methyl-CpG-Binding Protein 2;MicroRNAs;Missense Mutation;Modification;Molecular;Morphology;mouse genetics;mouse model;Mus;mutant;Mutation;Nervous System Disorder;Neurodevelopmental Disorder;Neurons;Neurosciences;novel;novel strategies;oligonucleotide delivery;Oligonucleotides;Outcome;Outcome Measure;overexpression;Pathogenicity;patient subsets;Patients;Pharmacologic Substance;Phenotype;posttranscriptional;prevent;Proteins;Pump;Reader;Regulation;Reproducibility;Research;response;restoration;Rett Syndrome;Risk;RNA-Binding Proteins;Role;Safety;safety assessment;Seminal;Series;Signal Transduction;Site;Sugar Phosphates;Surface;Symptoms;Synapses;Syndrome;Testing;Therapeutic;therapeutic development;therapeutic RNA;tool;Toxic effect;Training;transcriptome;Translating;Treatment Efficacy;Vertebral column;Viral;Viral Genes;virtual

PROJECT_TITLE: Targeting MeCP2-Associated Disorders with miRNA Site-Blocking Oligonucleotides

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03B-L (20)]


NIH_SPENDING_CATS: Cardiovascular;Dietary Supplements;Genetics;Heart Disease;Nutrition;Pediatric;Rare Diseases

PHR: Project Narrative The heart relies on specific nutrients like fatty acids to function normally and demonstrates metabolic flexibility (e.g., glucose utilization) in heart failure and altered nutrient environments. Multifactorial diseases like heart failure may be better understood in the context of inborn errors of metabolism (IEMs), a class of monogenic diseases caused by mutations in metabolic enzymes. Uncovering the consequences of LIPT1 deficiency, an IEM that can cause severe multi-organ dysfunction including cardiac failure, will enhance our understanding of the mechanisms driving heart failure and potentially uncover novel therapeutic opportunities.

PI_NAMEs: TIPPETTS, TREVOR STANLEY (contact)

PROGRAM_OFFICER_NAME: WANG, WAYNE C

PROJECT_TERMS: Acetyl Coenzyme A;Acute;Adult;Amino Acids;Anabolism;Animals;Atrial Fibrillation;Automobile Driving;Back;Bypass;Cardiac;Cardiac Myocytes;cardiogenesis;cardiometabolism;Cardiomyopathies;Cell Physiology;Cessation of life;Characteristics;Child;circulating biomarkers;Citric Acid Cycle;Clinical Data;cofactor;Consumption;data modeling;Defect;Development;Developmental Delay Disorders;Diet;Dietary Supplementation;Disease;Distress;Early Diagnosis;Early treatment;Echocardiography;Embryo;Energy Metabolism;Environment;Enzymes;epigenetic regulation;Exhibits;Failure;fatty acid oxidation;Fatty Acids;FDA approved;feeding;flexibility;Formulation;Functional disorder;Gatekeeping;Genetic Diseases;Genetic Recombination;Germ Lines;Glucose;Glycolysis;Heart;Heart Abnormalities;Heart failure;heart function;heart metabolism;Heart Rate;Histological Techniques;Histology;Impairment;improved;In Vitro;in vivo;Inborn Errors of Metabolism;Infant Mortality;Infection;Inflammatory;Investigation;Keto Acids;Ketoglutarate Dehydrogenase Complex;Ketone Bodies;Lead;lipid metabolism;Lipids;lipoate;Lipopolysaccharides;Mendelian disorder;Metabolic;Metabolic Diseases;Metabolic dysfunction;metabolic phenotype;Metabolism;metabolomics;Methods;Mitochondria;Modeling;Molecular;mouse model;Mus;mutant;Mutation;novel;novel therapeutics;Nutrient;Nutritional;Organ;Organism;oxidation;Oxidoreductase;Palmitates;Pathogenicity;Pathologic;Pathology;Patients;Phenotype;postnatal period;premature;programs;Proteins;Protocols documentation;Pyruvate;pyruvate dehydrogenase;Regulation;response;Sampling;Secondary to;Serum;Signal Transduction;Spirometry;stable isotope;stressor;succinyl-coenzyme A;Tachycardia;Testing;Therapeutic;Thioctic Acid;Tissues;Variant;Western Blotting;Work

PROJECT_TITLE: Using defective lipoylation as a window into cardiac fuel consumption and failure.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-K (20)]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Substance Misuse

PHR: PROJECT NARRATIVE Alcohol misuse is a leading cause of chronic liver disease; accordingly, rates of alcohol-related mortality have increased 23% since 2019 and progressive scarring of the liver is the main predictor of patient outcomes. The goal of this project is to elucidate novel mechanisms of alcohol-induced fibrotic gene reprogramming in the liver and identify specific factors amplifying liver scarring and disease progression, to provide a foundation for future clinical interventions to prevent or treat liver disease.

PI_NAMEs: RUTT, LAUREN  (contact)

PROGRAM_OFFICER_NAME: DUNTY, JR, WILLIAM

PROJECT_TERMS: Acceleration;Accounting;alcohol exposure;alcohol misuse;alcohol response;Alcoholic Liver Diseases;Alcohols;AODR mortality;Automobile Driving;beta catenin;Biological Process;Cells;Cessation of life;Chronic;chronic alcohol ingestion;chronic liver disease;chronic liver injury;Cicatrix;Cirrhosis;Clinical;Complex;crosslink;cytokine;Data;Death Rate;Deposition;Disease Progression;Embryo;Ethanol;Event;Extracellular Matrix;Felis catus;Fibroblasts;Fibrosis;Foundations;Future;Gene Expression;Genes;Goals;Grant;Hepatic;Hepatic Fibrogenesis;Hepatic Stellate Cell;Hepatic Tissue;Human;In Vitro;in vivo;Individual;injured;Injury;Intervention;kidney cell;Knockout Mice;Knowledge;Ligands;Literature;Liver;Liver diseases;Liver Fibrosis;liver inflammation;liver transplantation;Malignant neoplasm of liver;Measures;Modeling;Molecular;mortality;mouse model;Mus;Myofibroblast;novel;Pathogenesis;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern;Play;Prevalence;prevent;primary outcome;Production;protein expression;Proteins;receptor;Regulation;repaired;Resolution;response;response to injury;Role;Signal Transduction;Signal Transduction Pathway;Testing;Therapeutic;tissue injury;Tissues;toxicant;Transcription Coactivator;transdifferentiation;Transducers;Transforming Growth Factor beta;Transforming Growth Factors;United States;Wnt proteins;WNT Signaling Pathway;Wnt-3A protein;WNT5A protein

PROJECT_TITLE: Investigating the Role of Wnt3a and Wnt5a as Factors of Hepatic Stellate Cell Activation in Alcohol-Related Liver Fibrosis


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Aging;Bioengineering;Lung;Orphan Drug;Pulmonary Fibrosis;Rare Diseases

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE Idiopathic pulmonary fibrosis is a poorly understood progressive and fatal age-associated disease. This project will examine the role of senescent cells in matrix remodeling and tissue forces in a 3D bioengineered microtissue culture model of lung fibrosis. The results of this study will elucidate the role of fibroblast senescence in the development and progression of pulmonary fibrosis and identify potential druggable targets.

PI_NAMEs: NIEVES, ELISA B (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: 3-Dimensional;Age;age related;age related chronic disease;age-related disease;aged;aging mechanism;aging related;antifibrotic treatment;Apoptosis;Apoptotic;Area;Automobile Driving;beta-Galactosidase;Biomedical Engineering;CASP3 gene;CASP8 gene;cell motility;Cells;Chronic Disease;Collagen;cytokine;Cytometry;density;Development;Diagnosis;Disease;druggable target;Engineering;Etiology;Exposure to;Extracellular Matrix;Extracellular Matrix Proteins;FDA approved;Fibroblasts;Fibrosis;fibrotic lung;Flow Cytometry;Focal Adhesion Kinase 1;Human;human disease;Hydrogels;Hydrogen Peroxide;idiopathic pulmonary fibrosis;Image;Immunoassay;Immunofluorescence Immunologic;In Vitro;in vitro Model;Induction of Apoptosis;inhibitor;innovation;insight;kinase inhibitor;knock-down;Lung;Lung Diseases;Macrophage;Maintenance;Mass Spectrum Analysis;Measures;Mediating;Metalloproteases;microdevice;migration;Modeling;Myofibroblast;new therapeutic target;nintedanib;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Pirfenidone;prevent;Process;Production;Profibrotic signal;Progressive Disease;Pulmonary Fibrosis;Research;Resistance;Resolution;response;Role;senescence;senescence associated secretory phenotype;senescent cell;single cell analysis;Small Interfering RNA;Staurosporine;Stimulus;Structure;Structure of parenchyma of lung;System;Techniques;Therapeutic;Time;tissue culture;Tissue Model;Tissues;Work

PROJECT_TITLE: Engineering 3D microtissues of pulmonary fibrosis.


ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

ORG_STATE: CA

PHR: Project Narrative: Monoterpenoid bisindole alkaloids are a diverse group of natural products that display a rich assortment of bioactivities, including the ability to modulate protein–protein interactions in human cancer cells. The proposed research will develop strategies for the modular and convergent syntheses of bisindole alkaloids and non-natural analogs to enable biological investigations and structure activity relationship studies. The project will positively affect public health by granting access to this highly bioactive class of compounds to further our fundamental understanding of their bioactivity and facilitate the discovery of new anticancer lead compounds.

PI_NAMEs: GONZALEZ, KEVIN JAIME (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TITLE: Design and Application of Modular and Convergent Strategies for the Synthesis of Monoterpenoid Bisindole Alkaloids and their Analogs


ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE There is growing interest in whole genome sequencing of newborn genomes as a way to expand NBS to include hundreds of pediatric and actionable diseases (newborn sequencing, NBSeq). In order to reduce false negatives due to variants of unknown significance (VOUS), we will develop two massively parallel, rapid, and inexpensive methods to biochemical annotate the degree of misfolding and degradation of all versions of a protein in which each amino acid is substituted by all possible 19 other amino acids at one substitution per protein.

PI_NAMEs: GELB, MICHAEL H (contact);MALY, DUSTIN J

PROGRAM_OFFICER_NAME: PARISI, MELISSA

PROJECT_TERMS: Affect;Amino Acid Substitution;Amino Acids;Applications Grants;Bar Codes;Binding Proteins;Biochemical;Biological Markers;Blood;Cell membrane;Cells;cellular engineering;cellular targeting;Childhood;Chimeric Proteins;circular RNA;Collecting Cell;Collection;design;Disease;DNA;DNA Library;DNA Sequence;DNA Sequence Alteration;Dryness;Early Diagnosis;Elements;Engineering;Fluorescence;Fluorescence-Activated Cell Sorting;Frequencies;Functional disorder;Genome;genome sequencing;Goals;Golgi Apparatus;Grant;Human;interest;Libraries;Life;Measurement;Methods;Mitochondria;Neonatal;Neonatal Screening;new technology;Newborn Infant;next generation sequencing;Organelles;Pilot Projects;programs;protein degradation;protein folding;protein misfolding;Proteins;Public Health;Quality Control;Reporter;Reporting;RNA;Site;Spottings;System;Techniques;Technology;Transfection;Variant;variant of unknown significance;whole genome;Work

PROJECT_TITLE: Massively Parallel Biochemical Annotation of Missense DNA Variants to Support Newborn Screening by Whole Genome Sequencing

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MGG-L (02)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Eating Disorders;Mental Health;Neurosciences;Nutrition;Obesity

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative Dissecting the function of circuits controlling feeding is of vital importance to understand both adaptive eating as well as conditions such as obesity and anorexia. Here, we propose to investigate the function of a cell population in the midbrain that is not well-studied, but is a key control node of food-seeking, as shown in our preliminary data. Successful execution of these aims will provide deep functional characterization of a previously unknown circuit dedicated to food-seeking.

PI_NAMEs: ADHIKARI, AVISHEK  (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Affect;Anorexia;Appetitive Behavior;approach behavior;Axon;Behavior;Behavior Control;Binge Eating;Binge eating disorder;Biological;Biological Assay;Cells;Clinical;Collaborations;Computing Methodologies;Consumption;Data;Dedications;Desire for food;Disinhibition;Dissection;Eating;Eating Disorders;Exposure to;feeding;Feeding behaviors;Food;Fright;Future;Gryllidae;Health;hedonic;Human Resources;in vivo;Insecta;insight;Lateral;Link;Maintenance;Metabolic;Microscope;midbrain central gray substance;Midbrain structure;miniaturize;Modality;Molecular;Mus;neural;Neurons;neuroregulation;novel;Obesity;Optics;optogenetics;Outcome;Pathway interactions;Pattern;Population;Publications;Reporting;Research Personnel;Role;Slice;Source;Stimulus;Symptoms;Synapses;Testing;tool;Water;zona incerta

PROJECT_TITLE: GABAergic Cells in the Periaqueductal Gray Region Control Food-Seeking

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: Project Narrative Small molecule bioregulators are reactive species that are utilized by biology to regulate physiological functions through cellular signaling and molecular crosstalk. For some of these species, such as SNO– and SSNO–, the interconnectivity and their involvement in biological signaling pathways are still poorly understood due to their complexity and high reactivity in biological systems. This project will provide insight into how these reactive species can be stabilized which can inform on the reactivities and pathways these molecules engage in in physiological conditions.

PI_NAMEs: DAVIS, AMANDA G (contact)

PROJECT_TERMS: Acids;Affinity;analog;Anions;base;Binding;Binding Sites;Biological;biological systems;Biology;career;Cell Signaling Process;Charge;Chemicals;Chemistry;design;Development;driving force;Electrons;Environment;Exhibits;experimental study;Feedback;flexibility;functional group;Future;Goals;Hydrogen Bonding;Industry;insight;Investigation;Libraries;Manuscripts;Methods;Molecular;molecular recognition;Molecular Target;Nitrogen;Nitrogen Dioxide;novel;Outcome;Oxygen;Pathway interactions;Physiological;polysulfide;preference;rational design;Reaction;Reactive Nitrogen Species;Reactive Oxygen Species;receptor;Research;Role;Scientist;Signal Pathway;Signal Transduction;SKIL gene;small molecule;Sulfur;System;Thermodynamics;tool;Training;Training Activity;Work;Writing

PROJECT_TITLE: The Development of Novel Anion Receptors for Reactive Sulfur, Oxygen, and Nitrogen Species


NIH_SPENDING_CATS: Breast Cancer;Cancer;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and patients have less therapeutic options compared to other subtypes due to the lack of well-defined, targetable endocrine receptors. Efforts towards targeting other key components of this aggressive tumor subtype, namely macrophage-centered modalities, have had modest success due to TNBC distinct molecular subtypes and diverse macrophage heterogeneity. This research proposal will elucidate a link between the molecular profile of TNBC and macrophage origin and function to establish the tumor's molecular signature as a proxy for macrophage function.

PI_NAMEs: RIVAS, CHARLOTTE HELENA (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Ablation;Adoptive Transfer;aggressive breast cancer;Biological Assay;Bone Marrow;Bone Marrow Transplantation;cancer subtypes;Cells;Characteristics;clinically relevant;Color;Data;Disease;Embryo;embryonic stem cell;Endocrine;Epithelium;Exhibits;experience;experimental study;Flow Cytometry;Fluorescence-Activated Cell Sorting;Gene Expression Profile;Generations;genetic variant;Hematopoietic;Heterogeneity;Home;Human;immune cell infiltrate;Incidence;Induction of Apoptosis;innovation;Link;Macrophage;Maintenance;Malignant Breast Neoplasm;mammary;Mesenchymal;Modality;Molecular;Molecular Profiling;molecular subtypes;monocyte;Mus;Myelogenous;next generation;Patients;Persons;Play;Population;Positioning Attribute;preservation;Prevalence;prevent;progenitor;Property;Proxy;PTPRC gene;receptor;Recurrence;Reporting;Research Proposals;Role;Shapes;standard care;stem;success;Survival Rate;targeted treatment;Testing;Therapeutic;therapy development;therapy resistant;Tissues;transplant model;triple-negative invasive breast carcinoma;tumor;tumor microenvironment;tumor progression;Tumor Promotion;Tumor Subtype

PROJECT_TITLE: Unveiling how the molecular landscape of TNBC sculps intratumoral macrophage origin and function

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (20)]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: STANFORD

ORG_DEPT: BIOPHYSICS

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Mitochondrial Ca2+ signaling controls important cellular functions and is implicated in the pathogenesis of heart disease, but the regulation of mitochondrial Ca2+ uptake is not well understood. This study will investigate how key signaling molecules regulate mitochondrial Ca2+ uptake. Results obtained here will improve our understanding of mitochondrial Ca2+ signaling and inform the development of therapeutics designed to treat mitochondrial Ca2+ related diseases.

PI_NAMEs: MUIR, COLIN  (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: Binding;Biochemical;Biological Assay;Biophysics;Blood flow;Calcium;calcium uniporter;career;career development;Cause of Death;Cell Death;Cell Physiology;Complex;Complication;Cryoelectron Microscopy;Data;design;Development Plans;Disease;Dissociation;EF Hand Motifs;Environment;Enzymes;experience;experimental study;Goals;Healthcare Systems;Heart Diseases;Heart failure;improved;Inner mitochondrial membrane;innovation;insight;interdisciplinary approach;Ion Channel;Ions;Lipid Binding;lipidomics;Lipids;Liposomes;Mediating;Membrane Transport Proteins;Mentorship;Mitochondria;mitochondrial dysfunction;mitochondrial permeability transition pore;Modeling;Molecular;Molecular Conformation;Myocardial Ischemia;Necrosis;novel;oral communication;Oxidative Phosphorylation;Pathogenesis;Pathway interactions;Phospholipids;Physiological;Point Mutation;Positioning Attribute;prevent;Production;Proteins;Regulation;Reperfusion Injury;Research;Research Design;Research Training;Resolution;restoration;Role;Scientist;Signal Transduction;Signaling Molecule;skills;Structure;Tail;Techniques;Testing;Therapeutic;therapeutic development;Therapeutic Intervention;Tissues;Training;United States;uptake;Work;Writing

PROJECT_TITLE: Molecular insights into the regulation of mitochondrial calcium uptake

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


PHR: Project Narrative A key driver of cardiac bioenergetic abnormalities in heart failure is mitochondrial dysfunction, linked to depletion of mitochondrial NAD+, a vital metabolite required for aerobic metabolism. This proposal seeks to use cutting- edge biochemical, biophysical, and chemical biology approaches to interrogate how mitochondria maintain adequate NAD+ levels to preserve energetic homeostasis through the actions of an essential mitochondrial NAD+ transporter. This work will shed light on a pivotal mechanism dysregulated in disease and may suggest opportunities for countering mitochondrial dysfunction in the treatment of heart failure.

PI_NAMEs: KRISHNAN, ASWINI RAM (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Address;Architecture;Automobile Driving;Binding;Biochemical;Bioenergetics;Biology;Biophysics;blood pump;Cardiac;Cardiac Myocytes;Carrier Proteins;Cell Respiration;Cells;Cessation of life;Characteristics;Chemicals;Citric Acid Cycle;Coupled;Coupling;Cryoelectron Microscopy;Defect;Development;Dietary Administration;Disease;Electron Microscopy Facility;Elements;Energy Supply;Engineering;Environment;Failure;Family;global health;Heart;Heart failure;Homeostasis;Impairment;In Vitro;Incidence;innovation;insight;interdisciplinary approach;Interdisciplinary Study;Knowledge;Link;Liposomes;member;Membrane Proteins;Metabolic;Methods;Mitochondria;mitochondrial dysfunction;Mitochondrial Matrix;Molecular;Morbidity - disease rate;mortality;Nature;Pathway interactions;Phenotype;preservation;Process;protein function;protein purification;protein structure;Proteins;Protomer;reconstitution;Regulation;Research;Resolution;restoration;Role;Structure;System;Techniques;Therapeutic;Therapeutic Intervention;Toxic effect;Training;Transport Process;uptake;Work

PROJECT_TITLE: Molecular mechanisms of mitochondrial metabolic regulation


ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE Parkinson’s Disease (PD) is a neurodegenerative disease characterized by the loss of substantia nigra dopamine neurons, but our understanding of how their activity state contributes to their selective vulnerability is lacking. Using novel chemogenetic models to manipulate dopamine neuron activity in combination with mice that have disrupted dopamine storage, this proposal will deeply examine the role and mechanisms of neural activity in dopamine neuron susceptibility to dopamine-induced toxicity. Results from the proposed research will aid in the development of therapies to slow or prevent the loss of dopamine neurons and related motor symptoms in PD.

PI_NAMEs: RADEMACHER, KATERINA  (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: Agonist;alpha synuclein;Autoreceptors;Behavior assessment;Behavioral;Brain;Brain Diseases;Cells;Chronic;Clinical Research;Clozapine;Compensation;Corpus striatum structure;Coupled;Designer Drugs;designer receptors exclusively activated by designer drugs;Disease Progression;DNA Sequence Alteration;Dopamine;Dopamine D2 Receptor;dopaminergic neuron;effective therapy;Energy consumption;Exhibits;experimental study;Fiber;Functional disorder;Future;Gene Expression;Genetic;Genetic Models;Goals;Human;Hyperactivity;Impairment;improved;in vivo;insight;Lesion;Levodopa;Machine Learning;Measurement;Mediating;Metabolism;Midbrain structure;minimally invasive;Mitochondria;mitochondrial dysfunction;Modeling;monoamine;Motor;motor symptom;mouse model;mRNA Differential Displays;Mus;Nerve Degeneration;neural;Neurodegenerative Disorders;neuromechanism;Neurons;nonhuman primate;novel;oxidation;Oxides;Parkinson Disease;pars compacta;Pathology;Patients;Photometry;Predisposition;prevent;Process;Production;Proteins;Quinpirole;Research;Resolution;Rodent;Rodent Model;Role;sensor;Stress;Structure of subthalamic nucleus;Substantia nigra structure;Testing;Therapeutic;therapy development;tool;Toxic effect;Toxic Environmental Substances;transcriptomics;Transgenic Mice;Transgenic Organisms;treatment strategy;vesicular monoamine transporter;Work

PROJECT_TITLE: Elucidating the Role of Neural Activity in Midbrain Dopamine Neuron Degeneration

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03C-K (20)]


NIH_SPENDING_CATS: Brain Disorders;Cerebral Palsy;Cerebrovascular;Childhood Injury;Infant Mortality;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Social Determinants of Health;Stroke;Unintentional Childhood Injury

PHR: PROJECT NARRATIVE Neonatal brain injury remains the most common cause of infant mortality and morbidity in infants and children and is a tremendous public health problem. The Hershey Conference on Developmental Brain Injury brings together an international group comprised of leaders in this field, esteemed scientists from outside but related fields, as well as a high proportion of young trainees to continue the important discussions and dissemination of information constantly geared towards finding new and better modes of intervention and neuroprotection.

PI_NAMEs: JUUL, SANDRA E (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Acute;Address;Adult;Amaze;Area;Basic Science;Biological Markers;Birth;Brain;Brain Hypoxia-Ischemia;Brain Injuries;brain repair;Breathing;career;carina;Caring;Central Nervous System;central nervous system injury;Cerebral Ischemia-Hypoxia;Cerebral Palsy;Child;Clinical;clinical application;Clinical Trials Design;Collaborations;cost;Data;Dedications;Development;disability;Doctor of Philosophy;Educational workshop;Environment;ethnic minority;Europe;Experimental Models;Faculty;Family;Funding;Future;Goals;Human;Image;improved;Infant;infant morbidity/mortality;Infant Mortality;Information Dissemination;Injury;insight;Institution;International;Intervention;Ischemic Brain Injury;Knowledge;Learning;lectures;life time cost;Literature;Location;Machine Learning;Maintenance;meetings;Mentors;Molecular;National Institute of Neurological Disorders and Stroke;natural hypothermia;Neonatal Brain Injury;neuroprotection;Neurosciences;new therapeutic target;novel;Outcome;Participant;Patients;Pennsylvania;Perinatal Brain Injury;Perinatal Hypoxia;Perinatal mortality demographics;Persons;Physicians;Population;Postdoctoral Fellow;posters;Pre-Clinical Model;Premature Infant;Preterm brain injury;Prevention strategy;programs;Public Health;Publishing;racial minority;rational design;Recording of previous events;recruit;Relaxation;Research;Research Personnel;Retinopathy of Prematurity;Risk;Scientist;Signal Transduction;Site;Societies;Source;Stroke;Sweden;symposium;Technology;Translating;Translations;treatment strategy;Underrepresented Minority;United States National Institutes of Health;Update;Visit;Woman;Work

PROJECT_TITLE: 14th Hershey Developmental Brain Injury Conference

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-K (43)]


NIH_SPENDING_CATS: Genetics;Hematology;Human Genome;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CAMBRIDGE

ORG_DEPT: CHEMISTRY

ORG_NAME: HARVARD UNIVERSITY

PHR: PROJECT NARRATIVE ASXL1 is one of the most mutated genes in hematological disorders, but it is poorly understood how these mutations are mechanistically linked with these disorders as very little is known about the protein itself. In my preliminary studies, I discovered a degron that regulates the levels of ASXL1 protein, and this proposal will test if and how it regulates hematopoiesis. In the long term, this knowledge will advance our fundamental understanding of ASXL1’s role in primary hematopoiesis, how clinical mutations disrupt that process, and propel the development of new therapeutic strategies for a wide array of hematological disorders.

PI_NAMEs: SHEN, SIMON P (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Amino Acids;Biological Assay;Bohring syndrome;cardiovascular disorder risk;Cells;Chronic Myelomonocytic Leukemia;Clinical;Clonal Expansion;Clustered Regularly Interspaced Short Palindromic Repeats;Co-Immunoprecipitations;Collecting Cell;Complex;CRISPR screen;derepression;Development;Disease;Epigenetic Process;Excision;Exons;experimental study;Fluorescence;Fluorescence-Activated Cell Sorting;Frameshift Mutation;Future;Gene Expression;Genes;Genetic Diseases;genome editing;Guide RNA;Hematological Disease;Hematopoiesis;Hematopoietic;hematopoietic stem cell expansion;Hematopoietic stem cells;Hyperactivity;Individual;Investigation;Knock-out;Knowledge;Libraries;Link;Measures;Mediating;member;Modeling;Molecular;multicatalytic endopeptidase complex;Mutagenesis;Mutate;Mutation;Myeloproliferative disease;Nonsense Mutation;novel therapeutic intervention;Patient Selection;Phenotype;Point Mutation;Polycomb;Prevalence;Process;Prognosis;programs;Protein Truncation;Proteins;Recurrence;Reporter;Repression;risk stratification;Role;scaffold;single-cell RNA sequencing;small molecule;System;Testing;transcriptomics;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase;Ubiquitination;Western Blotting;Work

PROJECT_TITLE: Investigating the functional role of a degron in ASXL1 in hematopoiesis and disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-D (20)]