NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

PHR: PROJECT NARRATIVE In order to maintain genome integrity, our cells must continuously restrain the mobilization of “jumping genes” or transposable elements (TEs), in particular Long INterspersed Element-1 (LINE-1), the most active and influential mammalian TE. In this project, I will establish transcriptional decay by the RNA exosome complex as an unidentified yet critical repressor of LINE-1 activity in B lymphocytes and assess the downstream cellular consequences in the absence of this proposed silencing system. My anticipated findings will illuminate a new mechanism by which B cells prevent genome instability.

PI_NAMEs: LAURING, MAX CHEN (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Address;Affect;Affinity Chromatography;Antibodies;Apoptosis;Autoimmunity;Auxins;B-Cell Lymphomas;B-Lymphocytes;Bacteriophages;Binding Proteins;Biochemical;Biological;Biological Assay;Biology;career;Catabolism;Catalytic Domain;Cell Culture Techniques;Cell Line;Cells;Cellular biology;Clustered Regularly Interspaced Short Palindromic Repeats;Code;cofactor;Complex;Data;demethylation;derepression;Disease;DNA;DNA Methylation;DNA Transposable Elements;Doctor of Philosophy;embryonic stem cell;Endowment;Environment;Epigenetic Process;Event;Exhibits;exosome;experimental study;Fellowship;follow-up;Foundations;Functional disorder;functional loss;Future;Gene Expression;Genetic;Genetic Recombination;Genetic Transcription;Genome;genome integrity;genome sequencing;Genomic Instability;Genomics;Germ Cells;Goals;HCT116 Cells;Heterochromatin;Histones;Human;Human Genome;IGH@ gene cluster;immunodeficiency;Immunology;Immunoprecipitation;In Vitro;Influentials;Jumping Genes;Knock-in;Knowledge;lens;Long Interspersed Elements;Lymphoma;Malignant Neoplasms;Mammalian Cell;Mediating;Medical;Methyltransferase;Modification;Molecular;mouse genome;Mus;mutant;nanopore;National Research Service Awards;Paste substance;Pathology;Patient Care;Phenotype;Physicians;Play;Positioning Attribute;Predisposition;prevent;programs;Proliferating;Proteins;Pseudomonas aeruginosa;recruit;Regulation;restraint;Retrotransposition;Retrotransposon;RNA;RNA Decay;RNA Degradation;RNA Processing;RNA Stability;Role;Scientist;Somatic Cell;Source;stem cells;System;Testing;Time;Training;transcriptome sequencing;Universities;Untranslated RNA;Up-Regulation;whole genome;Work

PROJECT_TITLE: RNA Decay of LINE-1 Retrotransposons as a New Mechanism to Maintain B Cell Genome Integrity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07B-G (20)]


ADMINISTERING_IC: DA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Genetics;Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: IRVINE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTHER BASIC SCIENCES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Project Narrative Substance use disorders are chronic disorders often accompanied by persistent alterations to neural circuitry underlying reward and memory, leaving diagnosed individuals susceptible to relapse after prolonged periods of abstinence. Women and men differ in their biological and behavioral responses to drugs of abuse, and significant progress is needed to understand the molecular and epigenetic mechanisms underlying sex-specific, drug- induced alterations. The experiments in this proposal will examine how Gilz (glucocorticoid-induced leucine zipper), an X-chromosome linked gene, contributes to the establishment and reinstatement of cocaine- associated behaviors.

PI_NAMEs: ROUNDS, JACOB  (contact)

PROGRAM_OFFICER_NAME: FALCON-MORALES, EDGARDO

PROJECT_TERMS: Abstinence;Acute;addiction;Address;Affect;Behavior;behavioral response;Binding;Bioinformatics;Biological;Brain;Cell Physiology;ChIP-seq;Chromatin;Chronic;Chronic Disease;Cocaine;cocaine exposure;cocaine related behaviors;cocaine seeking;conditioned place preference;Cues;Data;design;Development;Diagnosis;DNA Binding;drug development;Drug Exposure;drug of abuse;drug seeking behavior;Enzymes;Epigenetic Process;experimental study;Fellowship;Female;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic Transcription;Glucocorticoids;Goals;HDAC3 gene;HDAC4 gene;Hippocampus;Histone Acetylation;Histones;Impairment;Individual;insight;Intravenous;knock-down;Knowledge;Leucine Zippers;Link;Literature;Long-Term Potentiation;male;Measures;Mediating;Memory;memory consolidation;men;Messenger RNA;Modeling;Molecular;Motivation;Mus;neural circuit;novel;Nucleus Accumbens;Pattern;Pharmaceutical Preparations;Phase;Play;Positioning Attribute;Postdoctoral Fellow;Predisposition;prolonged abstinence;Promoter Regions;Proteins;Protocols documentation;Relapse;Research;Research Personnel;response;Rewards;Rodent;Role;Saline;Self Administration;sex;Sex Differences;Substance abuse problem;Substance Use Disorder;Synaptic plasticity;System;Testing;Tissue-Specific Gene Expression;Training;transcriptome sequencing;transcriptomics;Viral;Vulnerable Populations;Woman;Work;X Chromosome

PROJECT_TITLE: Investigating the Role of Gilz, an X-linked Gene, in Regulating Cocaine-Induced Cellular Activity and Cocaine-Associated Memory

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02A-W (20)]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;Infectious Diseases;Prevention

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Coronavirus Infection Dynamics and Cross-species Transmission in Bats Newly emerged coronaviruses are a major threat to public health and understanding infection dynamics in reservoir bat hosts has the potential to inform on disease emergence and mitigation of epidemic and pandemic risk. This proposal will investigate host and environmental conditions facilitating cross-species transmission in wildlife sampled across Asia, Africa, and the Middle East. I will also prospectively collect data on bat-borne coronaviruses in diverse ecosystems locally in California (USA) and at an international field site (Myanmar) to assess seasonality, model disease dynamics, and investigate drivers of cross-species disease transmission.

PI_NAMEs: CORDS, OLIVIA  (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: 2019-nCoV;Africa;American;Asia;bat-borne;California;career;Characteristics;Chiroptera;Circulation;Collaborations;Communities;Complex;Coronavirus;Coronavirus Infections;Country;COVID-19 susceptibility;cross-species transmission;Data;data standards;Dedications;Disease;disease model;Disease Outbreaks;disease transmission;Ecology;Ecosystem;emerging virus;Environment;Epidemic;epidemic potential;epidemic response;Epidemiology;Event;Evolution;Exposure to;field study;Future;future pandemic;Genetic;Geography;Goals;Health;Home Ranges;Human;Immunologic Factors;Individual;Infection;insight;International;Lead;life history;Location;man;Methods;Middle East;Middle East Respiratory Syndrome Coronavirus;Modeling;Molecular;Myanmar;Nature;novel coronavirus;pandemic potential;Phylogenetic Analysis;Play;Population;Predisposition;Prevention;Process;prospective;Public Health;Reproduction;reproductive;Research Personnel;Risk;Risk Assessment;Risk Factors;Role;Sampling;SARS coronavirus;Seasons;Shapes;Site;southeast Asian;Structure;surveillance data;Taxon;Testing;Training;trait;transmission process;Viral;Virus;Virus Diseases;Work;Zoonoses

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07C-Y (20)]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: PATHOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE KMT2A-rearranged (formerly MLL-rearranged) leukemia is a particularly aggressive form of blood cancer that is often resistant to current chemotherapies, thus highlighting the need for better treatment strategies. We discovered that a key factor, called HMGA1, is required for KMT2A-r leukemic cells to grow and evade therapy. I now propose studies to determine how HMGA1 functions in KMT2A-r leukemia in order to develop better therapies.

PI_NAMEs: WEST, BAILEY  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: 11q23;academic preparation;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Binding;Biological Assay;career;career development;CDKN1A gene;Cell Cycle;Cell Cycle Progression;Cell Line;Cells;Chemoresistance;chemotherapy;Chimeric Proteins;Chromatin;chromatin immunoprecipitation;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Cyclin-Dependent Kinase Inhibitor;Cyclins;Cytarabine;Cytotoxic Chemotherapy;Data;Data Set;Development;effective therapy;efficacy testing;Environment;flavopiridol;Gene Expression;gene repression;Genes;Genetic Transcription;genomic locus;Hematopoietic;Hematopoietic Neoplasms;Histones;Homeobox Genes;HOXA10 gene;HOXA9 gene;Human;Human Cell Line;Implant;In Vitro;in vivo;inhibitor;innovation;Knowledge;Laboratory Finding;Learning;leukemia;Leukemic Cell;leukemogenesis;Lysine;Malignant Neoplasms;Manuscripts;Mediating;medical schools;MEIS1 gene;Methyltransferase;MLL gene;MLL-rearranged leukemia;Modeling;Molecular;mouse model;novel;novel strategies;novel therapeutic intervention;novel therapeutics;overexpression;Pathway interactions;patient derived xenograft model;Patients;Phenotype;Proliferating;Promoter Regions;Proteins;Publications;Publishing;recruit;Recruitment Activity;Refractory;Regulation;replication factor C;Reporter;Repression;Research;Research Personnel;Resistance;response;Role;small hairpin RNA;Techniques;Testing;therapy resistant;Training;transcriptome;transcriptome sequencing;Transgenic Model;treatment strategy;tumor;Tumor Suppressor Genes;Tumor Suppressor Proteins;Up-Regulation;Work

PROJECT_TITLE: Role of the chromatin regulator HMGA1 in KMT2A-rearranged leukemia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


NIH_SPENDING_CATS: Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: RICHMOND

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE The intracellular bacterium, Anaplasma phagocytophilum, causes the potentially fatal human infection, granulocytic anaplasmosis. This proposal will dissect how A. phagocytophilum exits host cells using a process known as regulated exocytosis as an essential step in disease progression. As numerous other pathogens and malignancies commandeer regulated exocytosis, the fundamental knowledge generated by this project could lead to novel therapeutic targets for treating diverse diseases.

PI_NAMEs: CHIARELLI, TRAVIS JOSEPH (contact)

PROGRAM_OFFICER_NAME: PERDUE, SAMUEL S

PROJECT_TERMS: Anaplasma;Anaplasma marginale;Anaplasma phagocytophilum;Anaplasmosis;Bacteria;Bacterial Proteins;Binding Proteins;Biological Process;Calcium;Calcium Binding;Cattle;Cell membrane;Cell Physiology;Cells;Cellular biology;Chemicals;Chloramphenicol;Communicable Diseases;Data;Development;Disease;Disease Progression;Dominant-Negative Mutation;Endosomes;Enzymes;Eukaryota;Exhibits;Exocytosis;exosome;extracellular;Face;granulocyte;Human;In Vitro;in vivo;Infection;inhibitor;Insulin;Integrin Binding;Knowledge;Link;Malignant Neoplasms;Mediating;Membrane;Microbe;microorganism;Molecular;Multivesicular Body;Mus;mutant;myristoylation;neurotransmission;neutrophil;new therapeutic target;novel;Organelles;overexpression;pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;pharmacologic;Phenotype;Plasmids;prevent;Process;Production;Productivity;Protein Biosynthesis;Proteins;Protozoa;Publishing;RBL2 gene;Reporting;Role;saliva secretion;Second Messenger Systems;Small Interfering RNA;sphingosine 1-phosphate;SPHK1 enzyme;Testing;Therapeutic;tick transmission;Ticks;Time;Tropism;Vacuole;Verapamil;Virus;Work

PROJECT_TITLE: Anaplasma phagocytophilum exploitation of regulated exocytosis.

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


ADMINISTERING_IC: EY

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Eye Disease and Disorders of Vision;Intellectual and Developmental Disabilities (IDD);Mental Health;Microbiome;Neurosciences;Pediatric

ORG_CITY: EUGENE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: PROJECT NARRATIVE The microbiome is emerging as an important determinant of brain development and these recent findings are prompting a paradigm shift in neuroscience. Microbial dysbiosis, which is frequently associated with neurodevelopmental disorders like autism, is also associated with aberrant visual processing, a commonly diagnosed comorbidity with autism. My goal in this proposal is to determine the role host-associated microbes play in visual system neurodevelopment, and to expand our overall knowledge on how the microbiome interacts with local cells in the gut to impact brain development.

PI_NAMEs: JAMES, DAVID M. (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Ablation;Anatomy;Attention deficit hyperactivity disorder;autism spectrum disorder;Automobile Driving;Behavior;Behavioral;Bioinformatics;Biological Models;Brain;Cell secretion;cell type;Cells;Central Nervous System;Communication;comorbidity;Complex;Cues;Data;Development;Diagnosis;Dominant-Negative Mutation;dysbiosis;effective therapy;Enteroendocrine Cell;Foundations;Functional disorder;gastrointestinal epithelium;Germ-Free;Glycoside Hydrolases;Gnotobiotic;Goals;gut bacteria;gut microbiome;Health;host-associated microbial communities;host-microbe interactions;Human;Individual;Interneuron function;Interneurons;Intervention;Intestines;Knowledge;Larva;Link;Location;Mediating;microbial;microbial products;microbiome;microbiota;Modeling;Molecular;Molecular Weight;mutant;Nature;nervous system development;neural;neurodevelopment;Neurodevelopmental Disorder;Neurons;Neurosciences;Outcome;Output;Pathway interactions;Peripheral;Phenotype;Photic Stimulation;Play;Population;prevent;Research;response;Role;Schizophrenia;Sensory;Shewanella;Signal Pathway;Signal Transduction;superior colliculus Corpora quadrigemina;Swimming;symbiont;Systems Development;Testing;Toll-like receptors;Vagus nerve structure;Vision;vision development;Visual;visual processing;visual stimulus;Visual System;Work;Zebrafish

PROJECT_TITLE: Microbiome Modulation of Visual System Development

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


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Rare Diseases;Rett Syndrome;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: PHYSIOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Rett syndrome (RTT) is a debilitating neurological disorder without cure caused by mutations of the MECP2 gene on the X chromosome. This proposal aims to apply CRISPR-based DNA methylation editing to restore healthy MeCP2 expression from the inactive X chromosome for the treatment of RTT in female patients. Understanding the extent of and mechanisms that govern this process will inform targeted epigenetic approaches to treat RTT and other X-linked disorders.

PI_NAMEs: PAN, RICHARD LI CHENG (contact)

PROGRAM_OFFICER_NAME: OREILLY, JULIA JIAQI

PROJECT_TERMS: Address;Adult;Affect;Age;Alleles;Behavioral;Binding;Binding Sites;Biology;Brain;career;CCCTC-binding factor;Cells;ChIP-seq;Chromatin Conformation Capture and Sequencing;clinical training;Clustered Regularly Interspaced Short Palindromic Repeats;Cognition;cognitive function;conditioned fear;CpG Islands;CRISPR/Cas technology;Data;demethylation;Deposition;Development;Disease;disease phenotype;DNA;DNA Methylation;Epigenetic Process;epigenetic silencing;epigenome editing;fear memory;Female;Flow Cytometry;Future;Genes;Genetic;Hematologic Neoplasms;Heterozygote;Hippocampus;Histone Deacetylation;Histones;Hybrids;Image;Immunofluorescence Immunologic;Impaired cognition;improved;In Vitro;in vivo;Injections;insight;Link;loss of function;Malignant neoplasm of gastrointestinal tract;Mammalian Cell;Mediating;Medical center;memory retrieval;Mentors;Methyl-CpG-Binding Protein 2;Methylation;Modeling;Molecular;mosaic;Motor;Motor Skills;mouse model;Mus;mutant;Mutation;nerve stem cell;Nervous System Disorder;Neurodevelopmental Disorder;Neurons;novel therapeutic intervention;Onset of illness;Patients;Phenotype;Physicians;Polycomb;Process;promoter;recruit;Reporter;restoration;Rett Syndrome;Scientist;Seizures;side effect;Site;skills;Stains;System;Therapeutic;tool;Training;Universities;women patients;X Chromosome;X Inactivation

PROJECT_TITLE: Epigenetic and Neuronal Mechanisms of MECP2 Reactivation to rescue Rett Syndrome

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biotechnology;Genetics;Neurosciences

PHR: Project Narrative: Proprioception encodes the perception of body and limb position, which is critical for motor behaviors and reflexes. Despite the essential nature of this sense, our understanding of how proprioceptive signals are transmitted into the spinal cord to regulate movement is not clear. The experiments proposed herein, will investigate the mechanisms through which the voltage-gated sodium channel, NaV1.6, shapes proprioceptive signaling.

PI_NAMEs: ESPINO, CYRRUS MAXWELL (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: Acute;Affect;Afferent Neurons;Animals;autism spectrum disorder;Axon;Behavior;Biochemistry;biophysical properties;Biophysics;Body Image;Brain;candidate selection;cell type;Cells;Closure by clamp;Communities;comorbidity;conditional knockout;CRISPR/Cas technology;Data;design;Disease;Electrophysiology (science);Engineering;Epilepsy;experimental study;Feedback;Fellowship;Gene Knock-Out Model;Genes;Genetic;genetic manipulation;Goals;Golgi Tendon Organs;Guide RNA;Human;Immunohistochemistry;Impairment;in silico;In Vitro;in vivo;Intramuscular;Ion Channel;Knock-out;knockout animal;Knowledge;Life;Limb structure;Mediating;model development;Modeling;Molecular;Molecular Biology;Motor;motor behavior;motor control;Movement;Mus;Muscle;Muscle Spindles;National Institute of Neurological Disorders and Stroke;Nature;Nervous System;Nervous System Disorder;Neurons;Neurosciences;neurotransmission;Organ;patch clamp;Pattern;Peripheral;Piezo 2 ion channel;Play;Population;Positioning Attribute;Postdoctoral Fellow;Posture;Property;Proprioception;Proprioceptor;Protein Isoforms;Publications;Ramp;Ranvier's Nodes;Reflex action;Reporting;Research;RNA delivery;Role;SCN1A protein;SCN8A gene;Sensory;Shapes;Signal Transduction;Skeletal Muscle;Sodium;Sodium Channel;Spinal;Spinal Cord;Stretching;Symptoms;Techniques;Testing;tool;Training;transmission process;Viral;voltage;voltage clamp;Walking;Work

PROJECT_TITLE: The encoding of proprioceptive signaling by Nav1.6

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02B-Y (20)]


ADMINISTERING_IC: MH

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: Project Narrative Altered dopamine signaling is a major characteristic of many neurological and neuropsychiatric disorders including schizophrenia and Parkinson’s disease. Due to a limited understanding of dopamine biology in both healthy and diseased states, we lack effective treatments for these disorders. The newest dLight variants provide the ability to measure dopamine dynamics with unprecedented precision, and this proposal aims to characterize the performance of the newest versions of this sensor in regions throughout the brain in both healthy animals and offspring of a maternal immune activation disease model.

PI_NAMEs: ROSHGADOL, JACOB  (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Acceleration;Address;Affinity;Amygdaloid structure;Animal Disease Models;Animals;Atlases;Behavior;behavioral phenotyping;Benchmarking;Biology;Biosensor;Brain;Brain Diseases;Brain region;calcium indicator;Characteristics;cognitive process;Communities;conditioned fear;Corpus striatum structure;Critical Thinking;Data;Data Analyses;Databases;design;Development;Disease;disease model;Dopamine;dopamine system;dopaminergic neuron;effective therapy;efficacious treatment;Engineering;Event;Family;Functional disorder;Generations;Grooming;Hippocampus;Image;immune activation;Immunology;improved;in utero;In Vitro;in vivo;Inflammatory;insight;interest;Knowledge;Literature;Location;Measurement;Measures;Metadata;Methods;Modeling;multiplexed imaging;Nature;Nervous System Disorder;neural;Neuromodulator;neurophysiology;neuropsychiatric disorder;neuroregulation;Neurosciences;Neurosciences Research;new technology;novel;novel strategies;offspring;online resource;open source;open source tool;Optics;optogenetics;Outcome;Parkinson Disease;Pathology;Patients;Performance;Phenotype;Physiological;Play;Prefrontal Cortex;repetitive behavior;Research;Research Personnel;response;Rewards;Role;Schizophrenia;sensor;Shapes;Signal Transduction;skills;System;technological innovation;Technology;Testing;theories;Time;tool;Training;Translating;two photon microscopy;Variant;Visualization;Work

PROJECT_TITLE: Optimizing in vivo dLight recordings for investigating the influence of disease on dopamine signaling.


ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE Voltage-gated sodium channels (VGSCs) mediate action potential propagation and transduction in neurons, however, recent work has shown that VGSCs serve additional functions in non- excitable cell types and in the developing nervous system. The potential contribution of these “non-canonical” functions of VGSCs to the development of neurodevelopmental conditions remains unknown. This proposed work will use human induced pluripotent stem cell-derived brain organoids and genome engineering to investigate the molecular mechanism underlying non-canonical VGSC contributions to neurological development and disease.

PI_NAMEs: HELMS, KYLE  (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: 3-Dimensional;Action Potentials;Adhesions;Advocate;anti-epileptic agents;Astrocytes;Behavior;Behavior Disorders;behavioral impairment;Biological;Brain;career development;Cell model;cell motility;Cell Physiology;Cell Proliferation;cell type;Cells;Central Nervous System;Cerebrum;Chemotaxis;Childhood;childhood epilepsy;Clinical;clinical phenotype;clinically relevant;Cognition;Cognition Disorders;Communities;Cortical Malformation;Data;Defect;design;Development;differential expression;Disease;early onset;effective therapy;Engineered Gene;Epilepsy;epileptic encephalopathies;Fellowship;fetal;Foundations;gene therapy;gene-editing approach;Generations;Genes;genome editing;Genome engineering;Goals;Homeostasis;Human;human induced pluripotent stem cells;human model;Immune;Impaired cognition;Impairment;improved;infancy;Inflammation;information processing;innovation;Integral Membrane Protein;Interneurons;Intervention;Ions;Link;Medial;Mediating;Membrane;Metabolism;Methods;migration;Modeling;Molecular;Molecular Target;Morphology;mutant;Mutation;Neoplasm Metastasis;Nervous System;nervous system development;Neurodevelopmental Disorder;Neuroglia;Neurologic;neuronal circuitry;Neurons;novel;novel therapeutic intervention;Organoids;Pathogenicity;Pathology;Patients;Pattern;pharmacologic;Pharmacotherapy;Physiological;Physiology;Pregnancy;prime editing;Proliferating;protein complex;Proteins;Radial;Refractory;Regulation;Research Personnel;Role;Science;Seizures;Signal Transduction;single-cell RNA sequencing;Sodium;Sodium Channel;Specific qualifier value;synaptogenesis;Testing;Therapeutic;therapeutic target;Thinking;Time;Tissues;Training;transcriptomics;Variant;voltage;Work

PROJECT_TITLE: Interrogation of non-canonical roles of VGSCs in neurodevelopmental epilepsy


ADMINISTERING_IC: AA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Substance Misuse

ORG_CITY: WORCESTER

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Project Narrative This project contributes to public health by supporting early career alcohol investigators and disseminating advances in alcohol research in the context of the American Psychological Association's annual convention. The activities in this application will support the pipeline of new alcohol investigators and their career development, particularly those of backgrounds under-represented in research. In addition, the project will promote the rapid dissemination of new findings within the scientific community and to the broader community of psychologists.

PI_NAMEs: KELLY, LOURAH MARIE (contact)

PROGRAM_OFFICER_NAME: SHIRLEY, MARIELA

PROJECT_TERMS: addiction;Affect;Alcohol abuse;alcohol abuse therapy;alcohol and other drug;Alcohol consumption;Alcohol dependence;alcohol related problem;alcohol research;alcohol use disorder;Alcohols;American Psychological Association;Award;Behavior;Behavioral;career;career development;Clinical;Communication;Communities;cost;Development;Diagnosis;disadvantaged background;Drug usage;early experience;Event;Faculty;Fostering;Funding;Future;Goals;graduate student;Health Psychology;innovation;K-Series Research Career Programs;Learning;meetings;member;Mentors;National Institute of Drug Abuse;National Institute on Alcohol Abuse and Alcoholism;next generation;peer;peer networks;Peer Review;Postdoctoral Fellow;posters;preference;Prevention;Process;programs;psychologic;Psychologist;Psychology;Psychopharmacology;Public Health;Qualitative Methods;Request for Proposals;Research;Research Personnel;Research Support;Schedule;Science;Scientific Advances and Accomplishments;Scientist;social media;Societies;Strategic Planning;Substance abuse problem;substance use;symposium;Time;Travel;United States National Institutes of Health;virtual;Voice;Work

PROJECT_TITLE: American Psychological Association Annual Meeting Early Career Investigator Poster Session

STUDY_SECTION: AA

STUDY_SECTION_NAME: Neuroscience and Behavior Study Section[AA-4]


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Allergies have dramatically increased in developed countries in the last several decades and can lead to deadly reactions. These responses are driven by IgE, an antibody isotype whose fundamental biology is poorly understood. By elucidating the molecular and cellular mechanisms of IgE clearance, this project will provide insights into the persistence of allergy and highlight potential therapeutic targets.

PI_NAMEs: ZHOU, KENNETH  (contact)

PROJECT_TERMS: Acute;Adult;Affect;Affinity;Allergens;Allergic;analog;Anaphylaxis;Antibodies;antibody engineering;Antigens;Autoimmune;Autoimmunity;Basophils;Binding;Biology;Catabolism;cell type;Cells;Circulation;crosslink;Data;Developed Countries;Development;Dichloromethylene Diphosphonate;Disease;effective therapy;egg;Excision;experimental study;Exposure to;Fc Receptor;Flow Cytometry;Fluorescence;Food;food antigen;Food Hypersensitivity;Functional disorder;Glycoproteins;glycosylation;Goals;Half-Life;Human;Hypersensitivity;IgE;IgE Receptors;Immune;Immunity;Immunobiology;Immunoglobulin G;improved;Infection;Inflammation;Inhalation;insight;interest;Kinetics;Knockout Mice;Knowledge;Kupffer Cells;Lectin;Life;Liver;Macrophage;Mannose;mannose receptor;mast cell;Mediating;Mentors;Modeling;Modification;Molecular;mouse model;Mus;new therapeutic target;novel;outcome disparities;Ovalbumin;Parasites;Pathogenicity;Peripheral;Phagocytes;Plasma Cells;Play;Polymerase Chain Reaction;Polysaccharides;preservation;Prevalence;prevent;Process;Property;Proteins;Radioactive;Reaction;receptor;receptor binding;Recycling;Regulation;Research;Research Personnel;Research Project Grants;response;Role;Signal Transduction;single-cell RNA sequencing;Site;Spleen;success;sugar;Surface;Symptoms;Therapeutic;therapeutic target;Time;Tissues;Transgenic Mice;Transgenic Organisms;Yeasts

PROJECT_TITLE: Elucidating the Cellular and Molecular Mechanisms of IgE Catabolism


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biotechnology;Diabetes;Digestive Diseases;Regenerative Medicine

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Accessing the submucosal space within the wall of the gastrointestinal tract is an attractive minimally invasive method that could be used for the implantation of therapeutic devices and cell therapies. However, the biology of the submucosal space as a host for cell therapies is not well understood, limiting development of these technologies for clinical application. This proposal aims to develop new knowledge in this area, which will be critical for subsequent potential therapeutic human applications.

PI_NAMEs: OWYANG, STEPHANIE YUEN (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Allogenic;allotransplant;angiogenesis;Animal Model;Animals;Area;Autoimmune;Autoimmune Diseases;Biological Assay;Biology;biomaterial compatibility;Biopsy;Blood;candidate selection;Cell model;Cell Therapy;Cells;Circulation;clinical application;Constipation;Cytoprotection;Degenerative Disorder;Development;Device Designs;Devices;diabetes mellitus therapy;Diffusion;Disease;Dissection;Dose;Drainage procedure;Encapsulated;Endoscopy;Euthanasia;Evaluation;Excision;experience;Family suidae;Fibrosis;Flow Cytometry;Foreign Bodies;Future;Gastric Submucosa;gastrointestinal;Gastrointestinal Diseases;Gastrointestinal tract structure;Gastroparesis;Geometry;Goals;Greater sac of peritoneum;Hemorrhage;Histology;Human;Immune;Immune response;Immunosuppression;Implant;implant material;implantable device;implantation;improved;in vivo;in vivo evaluation;Incidental Findings;Infection;Inflammation;Infusion procedures;insight;Insulin;Insulin-Dependent Diabetes Mellitus;interest;intraperitoneal;islet;Islets of Langerhans;Islets of Langerhans Transplantation;Knowledge;Lead;Lesion;Lifting;Mediating;Methods;migration;minimally invasive;Modeling;Monitor;motility disorder;Normal tissue morphology;novel strategies;Nutrient;Obstruction;Outcome;Oxygen;Pancreas;Pathology;Perforation;Peritoneal;Phenotype;Physiological;porcine model;Portal vein structure;prevent;Procedures;regenerative therapy;Research;response;Rest;Reverse Transcriptase Polymerase Chain Reaction;Safety;single-cell RNA sequencing;Site;Stains;Stomach;subcutaneous;Subcutaneous Tissue;Submucosa;Techniques;Technology;technology development;Testing;Therapeutic;Therapeutic Uses;Time;Tissues;Training;Vascularization;Venous;Work

PROJECT_TITLE: Leveraging the Gastric Submucosa as a Host for Cell Therapies

STUDY_SECTION: DDK

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE The goal of this proposal is to understand the mechanism of how AAA+ protein disaggregases collaborate with molecular chaperones to target and dissolve toxic amyloid aggregates to maintain protein homeostasis. These studies propose to use both biochemical assays and cryo-electron microscopy to determine structural snapshots which identify how these AAA+ disaggregases interact with the Hsp70 molecular chaperone system to disaggregate substrate. Completion of this proposal will produce the very first high-resolution details to the disaggregation activity of a protein disaggregase and will lead a foundation to study how potentiated mutants can dissolve human-associated amyloid aggregates.

PI_NAMEs: FLORES, RACHEL L (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: 3-Dimensional;Adopted;Affect;Amyloid;amyloid formation;Appearance;assay development;ATP Hydrolysis;ATP phosphohydrolase;Binding;Biochemical;biological adaptation to stress;Biological Assay;Cell Aging;Cell Survival;Cellular Stress;Classification;Collaborations;Cryoelectron Microscopy;Data;Data Analyses;density;Family;flexibility;Foundations;Goals;Hand;Heat shock proteins;Human;insight;Institution;interdisciplinary approach;Knowledge;Lead;Life;Light;Mediating;member;misfolded protein;Modeling;Molecular;Molecular Chaperones;Molecular Conformation;mutant;N-terminal;Neurodegenerative Disorders;novel;Nucleotides;particle;Pennsylvania;Phenotype;Play;polypeptide;prevent;Process;protein aggregation;protein complex;Proteins;Proteolysis;proteostasis;reconstitution;Research;Resolution;Role;Running;Saccharomycetales;Stress;Structure;sup35;System;training opportunity;unfoldase;Universities;Variant;Work;Yeasts

PROJECT_TITLE: Mechanistic insight to the interaction between AAA+ disaggregases and the Hsp70 molecular chaperone system

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


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences;Prevention

ORG_CITY: ATLANTA

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Myopia is rapidly approaching pandemic levels worldwide. The proposed studies will use wild-type conditions, environmental (LIM), and pharmacological (atRA) myopia models to elucidate the role of scleral fibroblasts during refractive development in mice. In doing so, I will provide valuable insight into mechanisms driving myopia development that are downstream of retinal signaling, which is an ideal window for clinical intervention in myopia prevention and treatment.

PI_NAMEs: BENTLEY, MELISSA R (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Address;Affect;Animals;Anterior;Antibodies;Architecture;Automobile Driving;Biological Assay;Blurred vision;Cell Culture Techniques;Cell Differentiation process;Cell Proliferation;Cells;Characteristics;Chondroblast;Clinical;Collagen Fibril;Communities;Confocal Microscopy;Connective Tissue;Contact Lenses;Cues;Data;density;Development;Disease;emmetropization;Ensure;Environment;Event;Exposure to;Extracellular Matrix;Eye;Failure;feeding;Fibroblasts;Future;Glass;Glaucoma;Goals;Growth;Health;Hyperopia;Imaging Techniques;Immunofluorescence Immunologic;in vivo;inhibitor;insight;Institution;Intervention;Knowledge;Label;Learning;Left;Length;lens;lens induction;Light;Location;Measures;Metalloproteases;Modeling;Molecular;mouse model;multiphoton microscopy;Mus;Myofibroblast;Myopia;novel;Optic Nerve;Optics;Oral Administration;pandemic disease;Participant;Pathology;pharmacologic;Population;Postembryonic;postnatal;Preparation;Prevalence;prevent;Prevention;Process;Program Development;programs;Proliferating;Property;Proteoglycan;Public Health;Refractive Errors;Research;Research Personnel;response;Retina;Retinal Detachment;Risk;RNA;Role;Sclera;second harmonic generation imaging;Signal Pathway;Signal Transduction;skills;Spatial Distribution;Stains;Stimulus;System;Techniques;Testing;Thick;Time;Tissues;training opportunity;Tretinoin;Vision research;Visual Pathways;visual stimulus;Work

PROJECT_TITLE: Investigating the role of scleral fibroblasts in refractive development and myopia

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


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Orphan Drug;Orthopoxviruses;Rare Diseases

ORG_CITY: MINNEAPOLIS

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Narrative Monkeypox (mpox) virus (MPXV) is significant threat to public health with pandemic potential. However, FDA- approved smallpox antiviral drugs do not work effectively for treating MPXV infections. The development of chemically and mechanistically novel antiviral leads that are safe, potent and orally available in this project will set the stage for further pre-clinical development of MPXV drugs that may also contribute substantially to countering other orthopoxviruses.

PI_NAMEs: WANG, ZHENGQIANG  (contact);YANG, ZHILONG

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: absorption;Acute;Affect;analog;animal efficacy;Animal Model;Animals;Anti-viral Agents;Applications Grants;Back;Binding;Biochemical;Biological Assay;Biological Availability;Blood Chemical Analysis;Case Study;Cell Survival;Cells;chelation;chemical synthesis;Chemicals;clinical efficacy;Clinical Management;Collection;Country;crosslink;Cultured Cells;cytotoxicity;Data;Dedications;design;Development;Diazomethane;Disease Outbreaks;Dose;Drug Kinetics;efficacy study;Evaluation;Excretory function;experience;FDA approved;Fibroblasts;Future;Genes;Goals;Grant;Hematology;histopathological examination;Human;in vivo;Individual;interdisciplinary approach;Label;Lead;Letters;liver function;Maximum Tolerated Dose;Metabolism;Metals;Methods;Microsomes;Modeling;Molecular Target;Monkeypox;Monkeypox virus;Morbidity - disease rate;mortality;Mus;mutant;Mutation;Nature;novel;Oral;Organ;Orthopoxvirus;pandemic potential;penis foreskin;Permeability;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phenotype;Physiological;Plaque Assay;Plasma;Poxviridae;pre-clinical;preclinical development;process optimization;Property;Proteins;Proteomics;Public Health;recombinant virus;Reporter;Research;Resistance;Resolvase;response;screening;Series;Smallpox;Solubility;Structure;Structure-Activity Relationship;Symptoms;Testing;Therapeutic;tool;Toxic effect;Vaccinia virus;Validation;Viral;Viral Genome;virology;Virus;Virus Diseases;Virus Replication;Zoonoses

PROJECT_TITLE: Development of novel antivirals against mpox (monkeypox) virus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 DCAI-F (02)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Mental Health;Mental Illness;Neurosciences;Prevention;Psychosis;Schizophrenia

ORG_CITY: TALLAHASSEE

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: Project Narrative There is a great need for earlier diagnosis and more effective treatments of psychosis, but a lack of understanding of the underlying neural circuitry involved in the pathophysiology of psychosis is a major barrier to the development of effective treatment options. This project will examine the synaptic and functional details of a murine neural circuit that links hippocampal hyperactivity to overactive dopamine signaling and psychosis-associated behavior. The investigation on specific brain regions, pathways, and nerve cells will help fill the gap in knowledge of the underlying neurobiology of psychosis and aid our ability to ultimately identify early indicators of pathology and develop new and more targeted treatment options.

PI_NAMEs: MATHEWS, MEAGHAN NAVARRETE (contact)

PROJECT_TERMS: Address;Anatomy;Animals;Antipsychotic Agents;Architecture;Behavior;behavioral phenotyping;Biological Process;Brain;Brain region;career;cell type;Cells;Delusions;Development;difopein;Disease;Disinhibition;Dopamine;dopaminergic neuron;Dorsal;Early Diagnosis;Early identification;effective therapy;experience;Functional disorder;gamma-Aminobutyric Acid;Genetic;genetic manipulation;Goals;Hallucinations;Hippocampus;Human;Hyperactivity;inhibitor;insight;Investigation;Knock-out;Knockout Mice;Knowledge;Lateral;Learning;Light;Link;Measures;Mediating;Mental disorders;Mental Health;Methods;Modeling;molecular phenotype;mouse model;Mus;neural;neural circuit;Neurobiology;neuronal excitability;Neurons;neurotransmission;novel;Pathology;Pathway interactions;Peptides;Phenotype;Phosphorylation;Population;prevent;Property;Protein Family;Proteins;Psychoses;psychotic symptoms;reduce symptoms;Regulation;Research Personnel;Role;Schizophrenia;Signal Transduction;Structure;Symptoms;Synapses;targeted treatment;Techniques;Testing;tool;Transgenic Mice;Validation;Ventral Tegmental Area;Viral;virus genetics

PROJECT_TITLE: The dCA1-LS-VTA Pathway in 14-3-3 Deficiency Induced Hyperlocomotor Behavior and Overactive Dopamine Signaling


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

ORG_CITY: KANSAS CITY

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE Alcohol-associated liver disease (ALD) is a leading cause of liver failure with mortality rates projected to continuously increase over the next few years. As the average lifespan increases, the prevalence of chronic liver diseases like ALD increases especially in the older adult and elderly population. The proposed studies will help to elucidate the underlying mechanisms in which aging and alcohol consumption collaboratively influence and exacerbate the development of ALD by assessing the roles of TFEB-mediated autophagy and the involvement of the integrated stress response (ISR) mediated by ATF3 activation.

PI_NAMEs: WILLIAMS, SHA NEISHA  (contact)

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: activating transcription factor 3;Acute;Adenoviruses;Adipose tissue;Affect;Age;age group;age-related disease;aged;Aging;aging population;Alcohol consumption;Alcohol-Induced Disorders;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;Attenuated;Autophagocytosis;binge drinking;Biogenesis;biological adaptation to stress;Biological Assay;Catabolic Process;Cell Aging;cell injury;Cells;Cessation of life;Chronic;chronic alcohol ingestion;chronic liver disease;Cirrhosis;Complex;Data;Death Rate;Development;disease prognosis;effective therapy;Elderly;Endoplasmic Reticulum;endoplasmic reticulum stress;enzyme activity;Ethanol Metabolism;extend lifespan;Fatty Liver;FDA approved;feeding;Fibrosis;FRAP1 gene;Future;gain of function;Gene Expression;glucose metabolism;Goals;Hepatic;Homeostasis;Immune response;Impairment;in vivo;Induction of Apoptosis;Inflammation;Lead;Link;lipid metabolism;Lipids;Liver;Liver diseases;Liver Failure;liver function;liver inflammation;liver injury;liver metabolism;loss of function;Lysosomes;Malignant neoplasm of liver;Measurement;Mediating;Metabolic;Mitochondria;Modeling;Monitor;Mus;Oils;old mice;older adult;Organelles;Outcome;overexpression;oxidation;Oxidative Stress;Pathogenesis;Pathology;Pharmaceutical Preparations;Population;Predisposition;Prevalence;Primary carcinoma of the liver cells;Process;Proteins;Protocols documentation;Quantitative Reverse Transcriptase PCR;Research;response;Risk Factors;Role;small hairpin RNA;Stains;Stress;stressor;System;therapy development;transcription factor;Transcription Repressor;transcriptome sequencing;Triglycerides;Tumor Suppression;Work;World Health Organization

PROJECT_TITLE: Lysosome and integrated stress response in aging and alcohol-associated liver disease

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


ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: Narrative Obesity is a disorder leading to metabolic disease, which is pervasive and is reaching epidemic proportions in the United States. This proposal seeks to investigate the role of perineuronal nets regulating neurons in the ventromedial hypothalamus (VMH) that mediate body weight and glycemic control. These investigations will facilitate the creation of new avenues for the treatment of obesity and associated disorders including diabetes.

PI_NAMEs: RIOS, MARIBEL  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Adult;Affect;Animals;Axon;Behavior;Binding;blood glucose regulation;Body Weight;Brain;Brain-Derived Neurotrophic Factor;cell type;Cells;Clinical;Complex;Data;Dendrites;density;Desire for food;Diabetes Mellitus;dietary;Disease;Eating;Epidemic;Equilibrium;excitatory neuron;Exhibits;Extracellular Matrix;Fasting;feeding;Fluorescence;follow-up;Gene Expression;Gene Expression Profiling;Genes;Glucose;Glutamates;glycemic control;Glycoproteins;Homeostasis;hormonal signals;Human;Hyperglycemia;Hyperphagia;Hypothalamic structure;Insulin Resistance;Investigation;Link;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic hormone;Morbid Obesity;Mus;Mutant Strains Mice;neural network;neuronal survival;Neurons;Neurotrophic Tyrosine Kinase Receptor Type 2;Nutrient;Obesity;obesity treatment;Parvalbumins;Pattern;Physiological;Play;Population;postsynaptic;Process;receptor;Regulation;response;Rodent;Role;Signal Pathway;Signal Transduction;Site;Structure;Synapses;Synaptic plasticity;Testing;United States;Variant;Weight maintenance regimen;Wild Type Mouse;Wisteria

PROJECT_TITLE: Perineuronal Nets in the VMH Regulating Energy and Glucose Balance

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 EMS-B (02)]


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);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Mental Health;Neurodegenerative;Neurosciences;Sleep Research

PHR: PROJECT NARRATIVE Alzheimer’s disease (AD) is a debilitating and irreversible neurodegenerative disease associated with major disruptions to sleep, an essential and ubiquitous process in all animals. Recent works reveal there is a strong bidirectional relationship between loss of slow-wave sleep (SWS), the deepest sleep stage, and the pathological and cognitive features of AD. Here, I will investigate whether chronic pharmacological slow-wave activity (SWA) enhancement can improve pathology and disturbances to sleep-wake rhythms and sleep architecture (Aim 1), as well as rescue behavioral and biological measures of memory deficits (Aim 2) in a mouse model of AD.

PI_NAMEs: JIN, MICHELLE  (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Affect;Aftercare;Age Months;Agonist;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer’s disease biomarker;Amygdaloid structure;analysis pipeline;Animals;anti-depressive agents;APP-PS1;Award;Behavioral;Biological;Biological Markers;Brain;Characteristics;Chronic;Cognition;Cognitive;Cognitive deficits;cognitive performance;comparative;conditioned fear;Custom;Data;dentate gyrus;design;Disease;efficacy testing;Electroencephalography;Euthanasia;Exhibits;experimental study;Exposure to;FDA approved;Fellowship;Freezing;Goals;Hippocampus;Human;Impaired cognition;Impairment;improved;improvement on sleep;in vivo;interstitial;Intervention;Knowledge;Laboratories;Learning;Literature;Maps;Measures;Mediating;Memory;memory encoding;Memory impairment;memory retrieval;Microdialysis;Modeling;mouse model;Mouse Protein;Mus;National Research Service Awards;Nerve Degeneration;neural;Neurodegenerative Disorders;neuromechanism;Neuronal Dysfunction;Neurons;Pathologic;Pathology;Performance;Persons;Pharmaceutical Preparations;pharmacologic;Physicians;Physiological;Play;Process;Proteins;Research;Retrieval;Reuniens Thalamic Nucleus;Role;Saline;Scientist;Second-Generation Antidepressive Agents;Severities;Severity of illness;Shock;skills;Sleep;Sleep Architecture;Sleep disturbances;Sleep Stages;Sleep Wake Cycle;Slow-Wave Sleep;System;tau Proteins;Testing;Therapeutic;Training;treatment strategy;Visualization;Work

PROJECT_TITLE: Investigating the Impacts of Pharmacological Slow Wave Sleep Enhancement on Cognition and Memory Traces in an Alzheimers Disease Model

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01B-M (20)]


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Bioengineering;Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Colorectal cancer (CRC) is the 3rd most common cancer and the 2nd leading cause of cancer death. After surgery, patients receive chemotherapy, including a drug called oxaliplatin, to prevent the recurrence of cancer. Oxaliplatin benefits less than 10% of patients, but it causes disabling neurotoxicity (nerve damage) in over 90% of patients. This project aims to develop an artificial intelligence model to predict which patient would benefit from oxaliplatin so that clinicians can choose different regimens to maximize efficacy and minimize unnecessary side effects.

PI_NAMEs: FREEMAN, TANNER J.;LU, XINGHUA  (contact)

PROGRAM_OFFICER_NAME: WANG, YANLI

PROJECT_TERMS: Address;Adjuvant;Adjuvant Chemotherapy;Adjuvant Therapy;Adverse effects;Antineoplastic Agents;Artificial Intelligence;artificial intelligence model;Calibration;cancer care;cancer cell;Cancer cell line;Cancer Etiology;Cancer Patient;cancer recurrence;care costs;causal model;Cells;Cessation of life;chemotherapy;Classification;Clinical;Clinical Data;Clinical Decision Support Systems;clinical decision-making;Clinical Trials;cohort;Colon;colon cancer patients;Colon Carcinoma;Colorectal Cancer;Data;Decision Making;deep learning;deep learning model;Deterioration;Disabling;Disease;Double-Blind Method;drug response prediction;drug sensitivity;FDA approved;Fluorouracil;Foundations;Future;Gene Expression;Genome;genomic biomarker;High Prevalence;high risk;Impairment;improved;improved outcome;Incidence;individualized medicine;inquiry-based learning;insight;International;Language;Learning;Leucovorin;Life;Malignant Neoplasms;metastatic colorectal;Methods;Mining;Modeling;molecular drug target;molecular targeted therapies;neoplastic cell;nerve damage;neurotoxicity;novel;Oncology;Operative Surgical Procedures;oxaliplatin;Patients;Performance;personalized decision;personalized predictions;Pharmaceutical Preparations;Phase;precision oncology;predicting response;predictive modeling;prevent;Quality of life;randomized, clinical trials;Regimen;Resected;response;RNA;Sampling;side effect;Signal Transduction;Specificity;standard of care;success;System;Testing;Training;transcriptome;transcriptome sequencing;transcriptomics;Translating;translational medicine;treatment effect;tumor;Validation;Vertebral column

PROJECT_TITLE: Interpretable deep learning models for translational medicine Renewal

STUDY_SECTION_NAME: Special Emphasis Panel[ZLM1 AS-C (01)]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Genetics;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human;Wound Healing and Care

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Epidermal basal cells give rise to the stratified layers of the epidermis during homeostasis; however, upon wounding, epidermal basal cells undergo a transient transcriptional switch to express genes required for wound healing. The regulation of this transcriptional switch is unknown, but our research has shown that a key chromatin regulator, PRC1, represses genes specific for epithelial fate upon wound induction, suggesting that PRC1 regulation is responsible for the transcriptional switch observed in epidermal basal cells during re- epithelialization. By investigating the role of PRC1-mediated regulation of epidermal basal cells during wound healing, we will be able to elucidate the mechanisms that control the transient transcriptional switch and thus the epidermal basal cells’ ability to properly contribute to the re-epithelialization process.

PI_NAMEs: BRANCH, MEAGAN  (contact)

PROGRAM_OFFICER_NAME: VINCENT, ISAAH S

PROJECT_TERMS: Ablation;Address;Adopted;Adult;Affect;American;Artificial skin;Automobile Driving;Basal Cell;Biological Process;Cell Adhesion Molecules;Cell Line;cell motility;Cell Separation;Cells;Chromatin;chronic wound;Data;Defect;Development;Down-Regulation;E-Cadherin;Economic Burden;Embryonic Development;Ensure;epidermal stem cell;Epidermis;epigenetic regulation;Epithelial Cells;Epithelium;gene repression;Genes;Genetic Transcription;Genetically Engineered Mouse;healing;Histone H2A;Histones;Homeostasis;Hospitals;Human;Impairment;In Vitro;in vivo;Infection;Inflammation;Injury;keratinocyte;Knockout Mice;Lysine;Mediating;Mesenchymal;migration;Molecular;Monoubiquitination;Mus;Nature;Neoplasm Metastasis;novel;overexpression;Phenotype;Play;PRC1 Protein;Process;programs;Proliferating;Proteins;re-epithelialization;Regulation;repaired;Reporting;Repression;Research;response;Role;Sampling;Skin;skin barrier;Skin wound healing;small hairpin RNA;Stratum Basale;Technology;Testing;Tissues;Transcriptional Regulation;transcriptional reprogramming;transcriptome sequencing;tumor;United States;wound;wound care;wound closure;wound epidermis;wound healing;Wounded area

PROJECT_TITLE: The Epigenetic Regulation of Epidermal Stem Cells in Adult Skin Wound Healing

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10B-Q (20)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurosciences;Pediatric;Prevention;Social Determinants of Health

PHR: PROJECT NARRATIVE The detrimental effects of social isolation during COVID-19 on young brains was immediately evident in the rise of the loneliness epidemic, an increase in mental illness amongst adolescence, and the immergence of Hikikomori Syndrome, but the long-term effects of adolescent social isolation on neurodevelopment are unclear. Social deficits are an early predictor for development of psychiatric disorders and are linked to cognitive impairments, a symptom of psychiatric illnesses for which there are no available treatments. This proposal aims to elucidate neurodevelopmental impact of adolescent social isolation across lifespan at the level of the cell, circuit, and behavior, and to identify timepoints for prevention and treatment.

PI_NAMEs: BRAVO, ISABEL  (contact)

PROJECT_TERMS: Adolescence;Adolescent;Adult;Affect;Animals;Area;Attention;Bees;Behavior;Behavioral;behavioral response;Brain;brain shape;Cells;Cephalic;Cognitive;Cognitive deficits;cognitive development;cognitive function;cognitive performance;Complex;COVID-19;critical period;Data;Defect;density;design;designer receptors exclusively activated by designer drugs;Development;Disease;Early identification;Ensure;Epidemic;Etiology;Female;flexibility;Genetic;Genetic Models;group cooperation;high risk;Histology;House mice;Human;Impaired cognition;Impairment;Individual;Individual Differences;insight;Intervention;Knock-in Mouse;Label;life span;Light;Link;Loneliness;Long-Term Effects;Machine Learning;male;mature animal;Measures;Medial;Mediating;Mental disorders;Modeling;Mus;Neurobehavioral Manifestations;neurodevelopment;Neurons;Onset of illness;Opsin;optogenetics;Pan paniscus;Pattern;Performance;Personal Satisfaction;Play;Predisposition;Prefrontal Cortex;preservation;prevent;Prevention;psychiatric symptom;Reporting;resilience;Risk Factors;Risk Marker;Rodent Model;Role;Schizophrenia;schizophrenia risk;sex;Sex Differences;sexual dimorphism;social;Social Behavior;social cognition;Social Controls;social deficits;Social Environment;Social Interaction;Social isolation;Syndrome;Testing;Thalamic structure;Time;tool;Training;Transgenic Mice;Variant;Viral;Visualization;Withdrawal;Work

PROJECT_TITLE: Impact of social environment on cognitive development and thalamocortical maturation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02A-W (20)]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Childhood Leukemia;Clinical Research;Genetics;Hematology;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Despite advancements in treating isocitrate dehydrogenase (IDH) mutated acute myeloid leukemia (AML) with targeted differentiation therapy, oncogenic Nras mutations consistently predict resistance. This proposal will characterize the role of oncogenic Nras in IDH mutant AML leukemogenesis and responsiveness to differentiation therapy with the goal of identifying novel therapeutic targets for this high-risk patient group. Using clinically relevant mouse models and patient samples, this work will elucidate how signaling environments influence a cell’s differentiation state and how cell state subsequently influences response to differentiation therapy.

PI_NAMEs: GELFER, REBECCA  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Acute Myelocytic Leukemia;Affect;Bioinformatics;Biological;Biological Assay;bisulfite sequencing;Blood;Bone Marrow;Cell Differentiation process;Cell Separation;Cell Transplantation;cell type;Cells;Clinical;clinically relevant;combinatorial;Coupled;Data;Differentiation Antigens;differentiation in vitro;Differentiation Inducer;Differentiation Therapy;Disease;Disease remission;DNA Methylation;Ensure;Environment;Epigenetic Process;epigenomics;experimental study;FDA approved;Flow Cytometry;Genetic Transcription;Genetically Engineered Mouse;Genotype;Goals;Hematologic Neoplasms;Hematopoiesis;Hematopoietic;high risk;histone methylation;Hyperactivity;Immunophenotyping;Impairment;In Vitro;in vivo;inhibitor;insight;Isocitrate Dehydrogenase;Laboratories;Lentivirus Vector;leukemia;Leukemic Cell;leukemogenesis;Mediating;MEK inhibition;MEKs;Metabolism;metabolomics;Modeling;mouse model;Mus;mutant;Mutate;Mutation;Myelogenous;Myeloid Progenitor Cells;neutrophil;new therapeutic target;novel;Oncogenic;Outcome;Pathogenesis;Pathologic;Pathology;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phenotype;Physicians;Predisposition;Process;Production;progenitor;Prognosis;programs;Proliferating;Regulation;Research Proposals;Resistance;response;Role;Sampling;Scientist;Signal Transduction;Spleen;stem;stem cell differentiation;stem cells;Subgroup;Surface;Therapeutic;therapy resistant;Training;transcriptome sequencing;treatment response;Work;Xenograft Model

PROJECT_TITLE: Characterizing Oncogenic Nras in IDH1 Mutant AML Leukemogenesis and Therapeutic Responsiveness


NIH_SPENDING_CATS: Congenital Structural Anomalies;Kidney Disease;Pediatric;Polycystic Kidney Disease

PHR: Project Narrative Autosomal dominant polycystic kidney disease (ADPKD) is a multifactorial disease with poorly understood mechanisms. Our previous research implicates the ouabain-induced signaling pathway of the Na,K-ATPase as a contributor of cyst progression in ADPKD. This proposal uses novel animal models to begin uncovering the mechanisms behind this ouabain-induced Na,K-ATPase signaling in ADPKD and reveal targets for future ADPKD therapies.

PI_NAMEs: TRANT, JORDAN  (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: absorption;Acceleration;Adult;Affect;Affinity;Animal Model;animal model development;Architecture;Automobile Driving;Autosomal Dominant Polycystic Kidney;Back;Binding;Binding Sites;Blood;career;Caveolae;caveolin 1;cell dedifferentiation;Cell membrane;Cell Proliferation;cell type;Cells;Characteristics;Clinical;clinical practice;Complement;Complex;Coupled;Cyclic AMP;Cyst;Cystic Kidney Diseases;Dialysis procedure;Disease;disease phenotype;Disease Progression;Educational process of instructing;Embryo;End stage renal failure;Epithelial Cells;experimental study;Fellowship;Fluids and Secretions;Future;Genetic;Goals;Growth;Histology;Hormones;Human;Interruption;Ion Transport;Ions;Kidney;kidney cell;Kidney Transplantation;Knock-out;Laboratories;laboratory experience;Liquid substance;Mediating;medical schools;Mentorship;Microscopy;mouse model;Mus;Mutate;novel;Ouabain;Outcome;Pathway interactions;Patients;Phenotype;Physicians;Plasma Cells;Polycystic Kidney Diseases;Population;Protein Tyrosine Kinase;Proteins;receptor;renal epithelium;Renal function;Research;response;Role;Scientist;Signal Induction;Signal Pathway;Signal Transduction;Signal Transduction Induction;Signal Transduction Pathway;skills;Small Interfering RNA;src-Family Kinases;Techniques;Testing;Therapeutic;Therapeutic Intervention;Training;Translational Research;Wild Type Mouse;Work

PROJECT_TITLE: Mechanisms of cyst progression driven by Na,K-ATPase in autosomal dominant polycystic kidney disease (ADPKD).

STUDY_SECTION_NAME: Fellowships in Kidney, Urology, and Hematology[DDK-G]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Physical Injury - Accidents and Adverse Effects;Rural Health;Social Determinants of Health;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: CHAMPAIGN

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Project Narrative Severe increased intracranial pressure results in high levels of death and disability for affected individuals, particularly in low-income environments such as rural settings and regions lacking access to neurosurgical care. In this proposal, we aim to develop novel kinematic navigation tools and workflows that will enable first- responding doctors to provide emergency stabilizing treatment to affected individuals in need of transport to hospitals with access to neurosurgical care. We additionally aim to deeply investigate the principles of these new kinematic tools for other surgical approaches including brain biopsy and spine surgery.

PI_NAMEs: SMITH, ALEXANDER DANIEL (contact)

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: 3D Print;access disparities;Acute;acute care;Address;Affect;Aluminum;Anatomy;arm;Atlases;automated segmentation;Biopsy;Brain;Cadaver;care providers;Caring;Catheters;Cerebral Ventricles;Cessation of life;Clinical;computer science;Computers;cost;cost effective;Country;cranium;design;Development;Devices;disability;Doctor of Philosophy;Drainage procedure;Economic Burden;economic impact;Education;Emergency Care;Emergency Department Physician;Emergency Situation;Environment;Evaluation;Freedom;Hand;Healthcare;Hematoma;Hospitals;Human;Hydrocephalus;Image;image guided;Image-Guided Surgery;Improve Access;Income;Individual;injured;injury burden;instrument;instrumentation;Intervention;Intracranial Hypertension;Intracranial Pressure;kinematics;laptop;Life;Liquid substance;Location;Low income;Magnetic Resonance Imaging;Measurement;Measures;Medical;Medical Imaging;Military Personnel;Morbidity - disease rate;mortality;Names;Navigation System;Needle biopsy procedure;Neurologic;Neurological emergencies;Neurosurgeon;neurosurgery;novel;Operative Surgical Procedures;Pathologic;patient population;Patients;Performance;Physicians;pilot test;Positioning Attribute;Postoperative Period;pressure;prevent;preventable death;Procedures;Production;Protocols documentation;Provider;Public Health;Raspberry Pi;real-time images;Research;Resource-limited setting;Resources;robot control;Robotics;rural area;Rural Hospitals;rural setting;Safety;Scientist;service providers;Shoulder;Skin;Specimen;Spinal Fusion;Spine surgery;Stainless Steel;Subarachnoid Hemorrhage;Surface;Surgeon;Surgical Instruments;System;TBI treatment;Technology;Testing;Time;tool;Training;Training Programs;Trauma;Traumatic Brain Injury;Trephine hole;tumor;Ventricular;ventricular system;Vertebral column;Visual;Visualization;Visualization software;wireless communication

PROJECT_TITLE: Atlas Neurosurgical Navigation System for Low-Resource Settings

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Anxiety Disorders;Brain Disorders;Cardiovascular;Heart Disease;Mental Health;Mental Illness;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: CHARLESTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Project Narrative Patients diagnosed with Post Traumatic Stress Disorder (PTSD) have a greater than 2-fold chance of experiencing a cardiovascular disease (CVD) associated event. Understanding the physiological profile and interaction between cardiac macrophages and fibroblasts will provide critical information regarding the increased CVD risk these patients face. Evaluating the impact of PTSD on CVD development we will lay the groundwork to determine CVD risk in vulnerable patients.

PI_NAMEs: CORKER, ALEXA  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Address;Adrenergic beta-Antagonists;Back;behavioral phenotyping;Biochemical;Bioinformatics;Biological;Blocking Antibodies;Bone Marrow;Bone Marrow Cells;Bone Marrow Transplantation;Cardiac;Cardiac Myocytes;Cardiology;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Physiology;cardiovascular risk factor;Caring;Cause of Death;Cell Separation;Cells;Chronic;Chronic Post Traumatic Stress Disorder;Clinical;Clinical Research;Clinical Treatment;Communication;complex data;coronary fibrosis;cytokine;Data;Data Set;Deterioration;Development;Diagnosis;disability;Event;experience;Extracellular Matrix;Face;Fibroblasts;Fibrosis;foot;Foundations;Functional disorder;Future;Gelatinase B;Gene Expression;Health;Heart;Histologic;Homeostasis;Immune;Impairment;Incidence;Inflammation;inhibitor;innovation;irradiation;Left ventricular structure;Link;Literature;Macrophage;Measures;Mechanics;Mediating;Medical;Mentors;migration;Mission;MMP9 gene;Modeling;monocyte;mouse model;Mus;Myocardium;National Heart, Lung, and Blood Institute;Neurosciences;novel;PAR-1 Receptor;Pathologic;Pathway interactions;Patients;Phenotype;Physiological;Physiology;Play;Post-Traumatic Stress Disorders;preconditioning;Predisposition;Production;Proliferating;Quality of life;receptor;recruit;Regulation;Role;Shock;Signal Transduction;single cell sequencing;Sorting;Structure;Systems Biology;targeted treatment;Testing;Time;tool;Training;Translations;Transplantation;Trauma;traumatic event;trend;United States;United States National Institutes of Health

PROJECT_TITLE: PTSD-Induced Alterations on Cardiac Homeostasis

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


ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: PROJECT NARRATIVE Lymphatic malformations (LMs) due to somatic activating mutations in the KRAS gene lead to life-threatening symptoms such as pleural effusions, chylous ascites and chylothorax. The proposed research will be the first to investigate the role of the PA pathway and MMPs in the regression of lymphatic valves in LMs. This work may enable the development of therapeutics for LMs by identifying the downstream targets that directly cause valve loss.

PI_NAMEs: MASTROGIACOMO, DIANDRA  (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: absorption;Agreement;Alleles;Anatomy;Back;Birth;Blood Circulation;Breeding;Chest;Chylothorax;Chylous Ascites;Collaborations;Collagen;Collagen Type IV;combinatorial;comparison control;Data;Defect;Dermal;Development;Ear;Enzyme Activators;Enzymes;Excision;Extracellular Matrix;Extracellular Matrix Degradation;Extracellular Matrix Proteins;Fibronectins;FRAP1 gene;Gelatinase B;Gene Mutation;Genes;Genetic;Growth;Human;human RNA sequencing;Hyperactivity;ilomastat;In Vitro;in vivo;Incidence;Inherited;Inhibition of Matrix Metalloproteinases Pathway;Intercellular Fluid;Interstitial Collagenase;Knock-out;KRAS2 gene;KRASG12D;Laminin;laminin alpha5;Lead;Lentivirus;Lesion;Life;Liquid substance;Live Birth;Location;Lung;Lymph;lymph flow;lymph nodes;Lymphatic;Lymphatic Capillaries;Lymphatic Endothelial Cells;lymphatic malformations;Lymphatic System;lymphatic valve;lymphatic vasculature;lymphatic vessel;Lymphedema;Matrix Metalloproteinase Inhibitor;Matrix Metalloproteinases;Measures;Medical center;MEKs;Mesentery;millimeter;Mitral Valve;MMP14 gene;Modeling;mouse model;mTOR Inhibitor;Mus;Mutation;novel;novel therapeutics;Operative Surgical Procedures;Outcome;overexpression;Pathway interactions;Patients;pharmacologic;Pharmacotherapy;PI3K/AKT;Plasmin;Plasminogen;Plasminogen Activator;Pleural effusion disorder;postnatal;prevent;Proteins;pup;Quantitative Reverse Transcriptase PCR;Ras/Raf;Reflux;Reporting;Research;Respiratory Diaphragm;response;Role;shear stress;side effect;Signal Pathway;Signal Transduction;Sirolimus;Skin;Somatic Mutation;stromelysin 2;Symptoms;Tamoxifen;Testing;therapeutic development;Time;Tissue Harvesting;Tissues;Toxic effect;transcriptome sequencing;Up-Regulation;vector control;Work

PROJECT_TITLE: Plasminogen Activator Pathway in Lymphatic Malformations


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: PROJECT NARRATIVE In the rapidly evolving immune system, genetic variation between individuals, or intraspecific variation, is a major driver of differential responses to infection. Transposable elements occupy about half of the mammalian genome and are a major source of genetic variation. By characterizing the contribution of these elements to intraspecific variation in both the human and mouse adaptive immune system, we will improve our understanding of how the immune system evolves and derive novel insights into the gene regulatory networks underlying the adaptive immune response.

PI_NAMEs: CHOBIRKO, JASON D. (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: adaptive immune response;Adaptive Immune System;ATAC-seq;Automobile Driving;Bacteria;Bioinformatics;Biological Assay;Cancerous;candidate identification;CD8-Positive T-Lymphocytes;Cells;Communication;Complex;Critical Thinking;Data;Defense Mechanisms;Development;differential expression;Dissection;DNA;DNA Transposable Elements;Elements;Enhancers;Ensure;Evolution;experience;experimental study;Gene Expression;gene regulatory network;Gene Targeting;Genes;genetic element;Genetic Enhancer Element;Genetic Variation;Genome;genomic data;Genomics;Human;Human Genome;Immune;Immune system;improved;In Vitro;in vitro Assay;Inbreeding;Individual;Infection;Innate Immune System;innovation;insight;Interdisciplinary Study;Interferons;Link;Malignant Neoplasms;mammalian genome;Measures;migration;Mobile Genetic Elements;Molecular Biology;mouse genome;Mouse Strains;Mus;nanopore;novel;Organism;pathogen;Phenotype;Play;Population;Population Heterogeneity;Positioning Attribute;Postdoctoral Fellow;Primates;Production;Proliferating;Regulatory Element;Repetitive Sequence;Resources;response;Scientist;segregation;Signal Transduction;Signaling Molecule;single cell analysis;single cell ATAC-seq;single-cell RNA sequencing;skills;Source;T-Cell Activation;Time;Tissue-Specific Gene Expression;Training;trait;transcriptome;transcriptome sequencing;Universities;Variant;Virus;Work

PROJECT_TITLE: Impact of transposable elements on cis-regulatory variation in T cell activation

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


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Muscular Dystrophy;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Project Narrative Emery-Dreifuss muscular dystrophy type 1 (EDMD1) is a hereditary muscular dystrophy that causes profound atrial arrhythmia. EDMD1 is caused by loss-of- function mutations to the nuclear membrane protein emerin, but how emerin influences atrial cell health remains a mystery. We propose a new model system to study this disease, and will use this system to define how emerin is regulated by dynamic trafficking through the secretory pathway in human atrial cells.

PI_NAMEs: MELLA, JESSICA  (contact)

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TERMS: Acceleration;Actins;Affect;Arrhythmia;beta catenin;Binding;Biological;Biological Assay;Biological Models;Biomechanics;Cadherins;Cardiac;Cardiac Myocytes;Cell Differentiation process;Cell Line;Cell membrane;Cell model;Cell Nucleus;Cells;Cellular biology;Chromatin;Complex;Computer Analysis;Couples;Coupling;Cytoskeleton;Defect;Disease;emerin;Emery-Dreifuss Muscular Dystrophy;Engineering;experimental study;fitness;Functional disorder;Gene Expression;Gene Expression Regulation;Gene Mutation;gene regulatory network;Genetic Transcription;Genome;Health;Heart;Heart Atrium;heart defect;Human;human disease;human induced pluripotent stem cells;Imaging Techniques;induced pluripotent stem cell;Inherited;Intercalated disc;Intercellular Junctions;Investigation;Knock-out;Knowledge;Life;Link;live cell imaging;Locales;Location;loss of function;loss of function mutation;Measures;Mechanics;Mediating;Membrane Proteins;Modeling;Mus;Muscular Dystrophies;mutant;Mutate;Mutation;Myocardium;Nuclear;Nuclear Envelope;Nuclear Inner Membrane;Nuclear Lamina;Pathology;Pathway interactions;Phenotype;Positioning Attribute;prevent;programs;Proteins;Regulation;Research Personnel;response;RNA Computations;Role;Route;scaffold;Shapes;Skeletal Muscle;skeletal muscle wasting;Structure;System;Testing;Time;Tissues;tool;trafficking;transcription factor;Transcriptional Regulation;transcriptome sequencing;Transducers;vesicle transport

PROJECT_TITLE: Uncovering the function of emerin and its regulation by secretory trafficking in human cardiomyocytes


NIH_SPENDING_CATS: Aging;Biotechnology;Brain Disorders;Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Parkinson's Disease;Prevention

ORG_CITY: EAST LANSING

ORG_NAME: HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES

ORG_STATE: MI

PHR: Project Narrative (3 sentences) Striatal calcium voltage-gated (CaV)1.3 channels represent a novel molecular target for levodopa-induced dyskinesias (LID), which remains a serious complication to medical treatment of individuals with Parkinson disease (PD). Acknowledging that age is the greatest risk factor for PD and that there are sex-related differences in PD and LID, in the previous iteration of this R01 award we expanded our research program, aimed at validating this promising target, into male and female parkinsonian rats and nonhuman primates (NHPs) of advancing age demonstrating for the first time that when gene-therapy mediated CaV1.3 silencing is employed as a proactive precision therapy in the aging brain there is maintenance of a profound antidyskinetic benefit and a striking reversal of long-standing parkinsonian disability, particularly pronounced in aged NHPs. In this competitive renewal, we propose a set of studies directed at determining the capacity and/or limitations of reversing established LID, modeling exploration of the therapeutic efficacy of CaV1.3 silencing in two demographics of PD, specifically in those with idiopathic PD and those with young onset PD (YOPD).

PI_NAMEs: KORDOWER, JEFFREY H;MANFREDSSON, FREDRIC ;STEECE-COLLIER, KATHY  (contact)

PROGRAM_OFFICER_NAME: SIEBER, BETH-ANNE

PROJECT_TERMS: 20 year old;Adult;Adverse event;Age;aged;Aging;aging brain;Appearance;Autopsy;Award;Behavioral;Brain;brain tissue;Calcium;Calcium Channel;Cerebrospinal Fluid;Clinical;clinical application;clinically relevant;Complication;Corpus striatum structure;Data;Defect;demographics;Dependovirus;disability;disease model;dopaminergic neuron;Dose;Elderly;FDA approved;Female;Funding;Gene Silencing;gene therapy;Genetic;Genetic Transcription;Goals;Hand;Histologic;Idiopathic Parkinson Disease;improved;in vivo;Individual;insight;Intervention;Investigation;Involuntary Movements;L-DOPA induced dyskinesia;Levodopa;Logistics;Macaca;Maintenance;male;Manuscripts;Mediating;Medical;medical complication;Messenger RNA;middle age;Mitochondria;Modeling;Molecular;Molecular Target;molecular targeted therapies;Monkeys;Motor;motor deficit;Mutation;Neurons;Neurotoxins;nonhuman primate;novel;Oxidative Stress;Parkin;Parkinson Disease;Parkinsonian Disorders;parkinsonian non-human primate;parkinsonian rodent;Patients;Performance;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;PINK1 gene;pre-clinical;Precision therapeutics;prevent;Prevention;Prior Therapy;programs;Quality of life;Rattus;receptor;Recombinant adeno-associated virus (rAAV);Research;Resources;retrograde transport;Risk Factors;Sampling;Series;Severities;sex;Sex Differences;side effect;skills;small hairpin RNA;success;Testing;Therapeutic;therapeutic target;Time;timeline;Transgenes;Treatment Efficacy;treatment response;Tyrosine 3-Monooxygenase;validation studies;vector;voltage;Work

PROJECT_TITLE: Genetic Silencing of Striatal CaV1.3 Calcium Channels as a Potent Antidyskinetic Therapy for PD

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Epilepsy;Neurodegenerative;Neurosciences

PHR: Project Narrative Temporal lobe epilepsy (TLE) is a highly prevalent neurological disorder with associated cognitive comorbidities that represent a significant burden to quality of life. This proposal will investigate whether altered timing of hippocampal inputs contributes to memory impairments in a mouse model of temporal lobe epilepsy. Understanding how hippocampal synchrony supports cognitive performance and how this is disrupted in epilepsy will yield deeper insight into the basic mechanisms of learning and memory in addition to enabling future treatments that specifically target cognitive deficits in epilepsy.

PI_NAMEs: PHILIPSBERG, PAUL ANDREW (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Address;Affect;Animals;anti-epileptic agents;Axon;Brain;Brain region;cell type;Cells;Chronic;Code;Cognition;Cognitive;Cognitive deficits;cognitive performance;Communication;comorbidity;Control Animal;dentate gyrus;Development;Disease;Electrophysiology (science);entorhinal cortex;Epilepsy;experimental study;Future;Head;Health;Hippocampus;Impaired cognition;improved;Individual;information processing;insight;Learning;Link;Location;Measures;Medial;Mediating;Memory;Memory impairment;Methods;mouse model;Mus;Nature;Nervous System Disorder;neural;neural circuit;neural stimulation;new therapeutic target;novel;novel therapeutic intervention;Optics;optogenetics;Patients;Perforant Pathway;Performance;Phase;Play;Population;Process;Quality of life;Recurrence;Resistance;Role;Seizures;spatial memory;stellate cell;System;Temporal Lobe Epilepsy;Testing;theories;therapeutic target;tool;Viral;virtual reality;way finding

PROJECT_TITLE: Theta Phase-Locked Stimulation of Entorhinal-Hippocampal Inputs in Healthy and Epileptic Mice

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01A-V (20)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Genetics;Neurosciences;Nutrition;Obesity

ORG_DEPT: GENETICS

PHR: PROJECT NARRATIVE Disruption to the cilia, a small cell protrusion, in the feeding center of the brain causes obesity. In this research proposal, I will define how a ciliary GTPase regulates feeding behavior. A better understanding of satiety and appetite control will enable new strategies to combat obesity, a major public health concern.

PI_NAMEs: TERRY, TIFFANY T (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Ablation;Acute;Adult;American;Animal Model;Animals;appendage;appetite regulatory center;Body Weight;Body Weights and Measures;Cell Physiology;cell type;Cells;Cilia;ciliopathy;cilium biogenesis;combat;comorbidity;Complex;Coronary heart disease;cost;Data;Defect;Desire for food;Development;Disease;Eating;economic impact;energy balance;Energy Metabolism;Engineering;Exclusion;feeding;Feeding behaviors;Functional disorder;G-Protein-Coupled Receptors;Genes;Genetic;Genetic Diseases;Genetic Engineering;Genetic Models;Glucose;Goals;Guanosine Triphosphate Phosphohydrolases;Health;Homeostasis;Human;human model;Hunger;Hyperphagia;Hypertension;Hypothalamic structure;in vivo;Inherited;Insulin;Knowledge;Lead;Life;Link;LoxP-flanked allele;Mammalian Cell;Measures;Medical Care Costs;Metabolic;Metabolism;Microtubules;Mission;Morbid Obesity;Morbidity - disease rate;mortality;mouse model;Mus;Mutant Strains Mice;neural circuit;neuronal circuitry;Neurons;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;novel therapeutic intervention;Obesity;obesity in children;Overweight;Phenotype;Population;postnatal;prevent;Process;protein function;Proteins;psychologic;Public Health;Regulation;Research;Research Proposals;Role;Satiation;Signal Pathway;Signal Transduction;social;stem;Surface;Testing;Tissues;tool;United States National Institutes of Health;Variant;Weight maintenance regimen;Work

PROJECT_TITLE: The Critical Role of Ciliary ARL13B in Controlling Energy Homeostasis

STUDY_SECTION_NAME: Fellowships in Diabetes Endocrinology and Metabolic Diseases [DDK-E]


NIH_SPENDING_CATS: Bioengineering;Clinical Research;Contraception/Reproduction;Fibroid Tumors (Uterine);Women's Health Research

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: PROJECT NARRATIVE Uterine fibroids are noncancerous tumors that form within the uterus, affecting nearly 70 - 80% of women in their lifetimes, and are a major cause of severe pain, bleeding, and infertility. Yet, despite its high prevalence and significant disease burden, current treatment options are limited, relying primarily on surgical means of removal, with innovation hampered by a poor understanding of the underlying disease pathophysiology. Therefore, this research proposal seeks to establish fundamental knowledge regarding the structure, function, and mechanics of uterine fibroids through a multi-scale, multi-faceted engineering-based approach to directly improve the diagnosis and treatment of uterine fibroids.

PI_NAMEs: FODERA, DANIELLA M (contact)

PROGRAM_OFFICER_NAME: AHN, HELENA HYESOOK

PROJECT_TERMS: Address;Adhesions;Affect;Age;Architecture;Behavior;Biochemical;Biological Assay;biomechanical test;Biomechanics;burden of illness;Categories;Cell Adhesion;cell behavior;cell motility;Cells;Cellular Morphology;Classification;clinical translation;Collagen;Data;Detection;Development;Diagnosis;diagnostic tool;Diameter;Discipline of obstetrics;Disease;disease heterogeneity;Drug Delivery Systems;Early Diagnosis;Elastin;Endoscopes;Engineering;Evaluation;Excision;Exhibits;Extracellular Matrix;Female;Fiber;Fibroid Tumor;Focal Adhesion Kinase 1;Functional disorder;Future;Gene Expression;Goals;Growth;Gynecologic;Health;Hemorrhage;Heterogeneity;High Prevalence;Human;Image;improved;In Vitro;Infertility;innovation;kinase inhibitor;Knowledge;Leiomyoma;Length;Literature;Location;Maps;materials science;Measures;mechanical properties;Mechanics;mechanotransduction;Methodology;Muscle Fibers;Myometrial;myometrium;nanoindentation;novel;Operative Surgical Procedures;Outcome Measure;overexpression;Pain;Pathology;Pathway interactions;Patients;Pelvic Pain;pharmacologic;Phenotype;polyacrylamide hydrogels;Premature Labor;Process;Property;Recurrence;Research;Research Proposals;Role;Scheme;second harmonic generation imaging;Signal Pathway;Signal Transduction;Smooth Muscle;soft tissue;Spatial Distribution;Stains;Structure;therapeutic target;Tissues;tool;Total Hysterectomy;Traction Force Microscopy;transcriptome sequencing;tumor;tumor growth;Uterine Fibroids;uterine smooth muscle cell;Uterus;Variant;Woman;Work

PROJECT_TITLE: Biomechanics and mechanobiology of human uterine fibroids

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F06-L (20)]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Mental Health;Pediatric

ORG_CITY: SAINT LOUIS

ORG_DEPT: PSYCHOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Despite nearly all adolescents in the United States reporting they use social media, and nearly half reporting they use it almost constantly, mixed findings in the literature have prevented a clear understanding of how social media use is specifically associated with adolescent emotional development. The proposed investigation will use a nuanced multimethod approach, combining lab-based experiments—along with physiological indicators— and real-life ecological momentary assessment to understand how four distinct SMU types impact adolescent emotions, are intentionally used by adolescents to influence their feelings, and their association with the development of depressive symptoms. In taking a nuanced approach to understand how specific types of SMU are associated with distinct emotional experiences, both in controlled lab-based settings and in everyday life contexts, this study aims to inform future interventions that target healthy adolescent social media use.

PI_NAMEs: TUCK, ALISON  (contact)

PROGRAM_OFFICER_NAME: GALLEN, COURTNEY LEIGH

PROJECT_TERMS: Address;Adolescence;Adolescent;Adolescent Development;adolescent mental health;Affect;aged;Autonomic nervous system;Award;Belief;Benefits and Risks;career;Child Behavior;Child Development;Communities;Consumption;depressive symptoms;design;Development;digital;digital applications;digital media;Disease;Ecological momentary assessment;emotion regulation;Emotional;emotional experience;Emotions;experience;Experimental Designs;experimental study;Failure;Feeling;Fostering;Funding;Future;Goals;Habits;Image;insight;Intervention;Investigation;Knowledge;Learning Skill;Life;Literature;Measures;media use;Mental Depression;Mental Health;Methodology;Methods;Modeling;Monitor;negative affect;novel;Outcome;parent grant;Participant;Patient Self-Report;Personal Satisfaction;PF4 Gene;Physiological;Positioning Attribute;Postdoctoral Fellow;prevent;programs;Psychopathology;Recommendation;recruit;Regulation;Reporting;Research;Research Design;Research Personnel;respiratory;response;Risk;Sampling;Sinus Arrhythmia;skills;social media;Stress;Surveys;Testing;theories;Time;Training;United States;United States National Institutes of Health;Well in self;Withdrawal

PROJECT_TITLE: Associations Between Social Media Use and Healthy Adolescent Development

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F16-H (20)]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Mental Health;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: PHILADELPHIA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: DREXEL UNIVERSITY

PHR: Eviction is a common, inequitably distributed, and policy-sensitive driver of poor individual health outcomes that may also produce spillover effects on neighborhood health by exacerbating stress and disrupting protective social structures within communities. This mixed-methods study will draw on local and national data to examine whether, how, and for whom neighborhood-level eviction exposures affect individual-level cardiovascular health outcomes. This study will deepen our understanding of how eviction influences health (with implications for reducing health inequities) while also providing invaluable opportunities to expand the trainee’s conceptual knowledge, methodological skill, and ability to translate research findings to policy and practice improvement.

PI_NAMEs: SMITH, PATRICK DUNN (contact)

PROGRAM_OFFICER_NAME: CAMPO, REBECCA A

PROJECT_TERMS: Accounting;acute care;Adult;Affect;Ambulatory Care;Attention;Behavior;Black race;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;Censuses;Chronic;clinical practice;cohort;Cohort Studies;Communities;COVID-19 pandemic;Data;Data Analyses;Development;Disease Management;Epidemic;Equity;Ethnic Origin;Exposure to;Face;Financial Hardship;Funding;Gender;Goals;Growth;Health;Health behavior;health equity;Health Expenditures;health inequalities;Health Promotion;Healthcare;Home;Hospitalization;Housing;housing instability;improved;Individual;Inequity;innovation;Intervention;Interview;Judgment;Justice;Knowledge;Latinx;Legal;Link;Low income;marginalized population;member;Mental Health;Methodology;Methods;Modification;multilevel analysis;Neighborhoods;Nurses;Outcome;Participant;Pathway interactions;physical conditioning;Physiological;Policies;prevent;Process;protective factors;psychological distress;Psychosocial Stress;Race;Recommendation;Recording of previous events;Research;Research Infrastructure;Research Personnel;Resources;Risk;Risk Factors;Sampling;skills;Smoking;social structure;Social support;sociodemographic factors;Stress;stress management;Structural Racism;Surveys;Testing;Time;timeline;Training;Translating;United States National Institutes of Health;Woman;Work

PROJECT_TITLE: Understanding Neighborhood Effects of Eviction on Cardiovascular Health: A mixed-methods study

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F18-E (20)]


ED_INST_TYPE: UNIVERSITY-WIDE

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

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Mutations in Chromodomain Helicase DNA-binding protein 8 (CHD8) have a strong causal association with autism spectrum disorder (ASD), but the cell-type specific molecular phenotypes that drive ASD-relevant pathology are uncertain. Further, previous studies of human ASD patients, including CHD8 mutants, suggest a presence of immune dysfunction, but the effects of CHD8 haploinsufficiency on microglia have yet to be defined. This proposal will help elucidate cell type-specific changes in gene expression linked to Chd8 haploinsufficiency in the mouse brain and clarify its relationship to immune function, thereby enhancing the current understanding of mechanisms underlying autism and identifying potential targets for treatment or preventative measures.

PI_NAMEs: LOZANO, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: OREILLY, JULIA JIAQI

PROJECT_TERMS: Adult;Affect;age related;ASD patient;autism spectrum disorder;Autopsy;Behavioral Symptoms;Binding;Biological Assay;Brain;Brain Diseases;Cell Nucleus;cell type;Cells;Characteristics;chromatin remodeling;Chromatin Remodeling Factor;cognitive function;cohort;cytokine;Data;debilitating symptom;Development;Developmental Process;Diagnosis;differential expression;disease model;DNA-Binding Proteins;dosage;Embryo;Exhibits;exome;Fluorescent in Situ Hybridization;Functional disorder;Future;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic signature;Genetic Transcription;Genome;Germ Lines;glial activation;Goals;helicase;Heterozygote;HLA-DR Antigens;Human;Immune;immune function;Immune response;Immune System Diseases;Immunohistochemistry;in vitro Model;Independent Living;Individual;insight;Intellectual functioning disability;knock-down;Knowledge;Link;loss of function mutation;Loss of Heterozygosity;Macrocephaly;Maps;Mediating;Microglia;Modeling;Molecular;molecular pathology;molecular phenotype;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;mutation carrier;Neonatal;Neurobehavioral Manifestations;neurodevelopment;Neurodevelopmental Disorder;neurogenesis;Neuroglia;Neuroimmune;Neuroimmunomodulation;neuroinflammation;Neurons;novel;Ontology;Pathogenesis;Pathologic;Pathology;Pathway Analysis;Pathway interactions;Patients;Phenotype;Population;postmitotic;Preparation;prevent;Preventive measure;Probability;Process;programs;Proteins;Publishing;Research;risk variant;RNA;Running;Sampling;Secondary to;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;Sleep;Stress;Surveys;Symptoms;synaptic function;Testing;Therapeutic Intervention;Time;Tissue-Specific Gene Expression;transcriptome;transcriptome sequencing;transcriptomic profiling;transcriptomics;Validation;Wild Type Mouse;Work

PROJECT_TITLE: Mapping the cellular impacts of Chd8 haploinsufficiency and characterizing microglial activity in Chd8 mutant mice

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


NIH_SPENDING_CATS: Biomedical Imaging;Data Science;Mental Health;Neurosciences

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: YALE UNIVERSITY

PHR: PROJECT NARRATIVE The neuroimaging field is currently in the midst of a power problem. Without sufficient increases in power, predictive utility of connectomes, including for clinical applications, remains low. I propose improvements to network-level statistical methods for human functional and structural connectomes to improve statistical power.

PI_NAMEs: RODRIGUEZ, RAIMUNDO XAVIER (contact)

PROGRAM_OFFICER_NAME: CHURCHILL, JAMES D

PROJECT_TERMS: Age;Benchmarking;Brain;brain behavior;Brain region;Clinical;clinical application;clinically relevant;cohort;Complex;connectome;Data;data acquisition;Data Science;Data Set;Derivation procedure;Development;Diffusion Magnetic Resonance Imaging;diverse data;Future;Goals;Hand;Handedness;Human;improved;Individual;large scale data;Lead;Literature;Magnetic Resonance Imaging;Mental Health;Methodology;Methods;Modality;model building;neuroimaging;Neurosciences;Noise;Paper;Performance;personalized medicine;Phenotype;Philadelphia;Population;Procedures;Publications;Research;Research Personnel;Rest;risk prediction;risk stratification;Running;Sample Size;sex;Signal Transduction;Statistical Data Interpretation;Statistical Methods;statistics;structural imaging;Structure;Techniques;Testing;tool;Training;Work

PROJECT_TITLE: Improving statistical power for human structural and functional connectomes

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


NIH_SPENDING_CATS: Autism;Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Controlling when and where DNA is expressed is critical for correct human development, as evidenced by the many disorders associated with altered gene expression. Our study aims to understand how this expression is controlled normally, and how it goes awry in neurodevelopmental disorders, so that therapeutic approaches can be identified.

PI_NAMEs: PEIRENT, EMILY ROSE (contact)

PROJECT_TERMS: Affect;autism spectrum disorder;Biological Assay;Biology;Brain;Cell Differentiation process;Cell Line;Cells;Cerebrum;Chromatin;chromatin modification;Cleavage Under Targets and Release Using Nuclease;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complement;Complex;critical period;Data;Development;Disease;disease model;DNA;Dorsal;Elements;epigenetic regulation;Etiology;Exhibits;Family member;Gene Expression;Gene Silencing;Genes;Genetic;Genetic Transcription;genome-wide;genomic locus;Genotype;Goals;Heterozygote;Histone H2A;histone methylation;histone modification;Histones;Human;Human Development;human model;human pluripotent stem cell;Hydrolase;Immunohistochemistry;In Vitro;in vitro Model;Knowledge;Ligation;Link;Lysine;Modification;molecular pathology;Monoubiquitination;Mus;nerve stem cell;neurodevelopment;Neurodevelopmental Disorder;neurogenetics;neuromechanism;Neuronal Differentiation;Neurons;neuropathology;neuroregulation;Organoids;Pathogenicity;Pathology;Patients;Pattern;Polycomb;PRC1 Protein;Pregnancy;progenitor;Proliferating;Prosencephalon;Proteins;Regulation;single-cell RNA sequencing;spatiotemporal;stem cell differentiation;stem cell expansion;Structure;Syndrome;Therapeutic;Transcription Elongation;Transcriptional Regulation;transcriptome sequencing;Ubiquitin;ubiquitin isopeptidase;Variant;Work

PROJECT_TITLE: ASXL3 Links Chromatin Biology to Neurodevelopment Disorders


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences

ORG_CITY: NEW YORK

PHR: Project Narrative Cognitive decline during aging involves impairments in using stored information to support learning in new environments, leading to decreased behavioral flexibility. This proposal will investigate whether the similarity between cognitive maps in the dorsal CA1 region of the hippocampus changes as mice accumulate multiple cognitive maps across different age groups. Understanding how similarity between cognitive maps aids in behavioral flexibility is critical to understanding the neural signaling alterations that underlie cognitive decline and can pave the way for therapeutic interventions that will improve the quality of life for an aging population.

PI_NAMEs: BAGGETTA, AUSTIN  (contact)

PROGRAM_OFFICER_NAME: THOMAS, CIBU PAUL

PROJECT_TERMS: Action Potentials;Affect;Age;age group;aged;Aging;aging population;animal old age;Animals;Behavior;Behavioral;behavioral impairment;Behavioral Paradigm;Brain;Calcium;Cells;Code;Cognitive;Cognitive deficits;Data;Dorsal;Environment;experience;Fire - disasters;flexibility;Future;Goals;Hippocampus;Image;Impaired cognition;Impairment;improved;in vivo calcium imaging;Individual;innovation;insight;Intervention;Knowledge;Learning;Link;Literature;Location;Maps;Measurement;Memory;Microscope;middle age;Mus;neural;neuromechanism;Neurons;neurotransmission;normal aging;novel;old mice;Pattern;Persons;Population;Probability;Problem Sets;Process;Proteins;Quality of life;Resources;Rewards;Rodent;Speed;Testing;Therapeutic Intervention;transcription factor;vector;Visual;Water;way finding;Work;young adult

PROJECT_TITLE: How does the brain accumulate cognitive maps?

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01B-E (90)]