NIH_SPENDING_CATS: Genetics;Human Genome;Nutrition

ORG_CITY: IRVINE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: PROJECT NARRATIVE Transposable elements are selfish genetic elements that occupy nearly half of the human genome and have been associated with inherited diseases, cancer, and aging-associated diseases. This proposal will identify dietary factors that influence organisms’ defense mechanisms against transposable elements and investigate the consequential functional and health outcomes. Findings from this proposal will provide a novel perspective for gauging the full impact of how nutrition impacts health, which is critical to guiding dietary choices and interventions that support human health and prevent disease.

PI_NAMEs: LEE, GRACE YUH CHWEN (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Accounting;Address;Adverse effects;aging related disease;Biological Models;Calories;Carbohydrates;Categories;Chromatin;cofactor;Data;Defense Mechanisms;Deposition;design;Development;Diet;dietary;dietary control;Dietary Factors;Disease;DNA Insertion Elements;DNA Transposable Elements;Drosophila genus;Elements;Enzyme Inhibitor Drugs;Enzymes;Epigenetic Process;epigenetic regulation;epigenetic silencing;epigenomics;Equilibrium;Evolution;Exclusion;Experimental Genetics;Fatty acid glycerol esters;Fertility;fitness;Fluorescence;functional genomics;functional outcomes;Genes;genetic element;Genetic Polymorphism;Genome;genome-wide;genomic data;Genomics;Health;Hereditary Disease;Human;Human Genome;Impairment;Individual;inhibitor;Intervention;Investigation;ketogenic diet;Knowledge;Malignant Neoplasms;Mammals;Mediating;Modeling;Modification;Movement;mutant;novel;Nutrient;nutrition;Organism;Outcome;Parasites;Pharmacologic Substance;Phenols;Physiology;Positioning Attribute;prevent;Proteins;Reporter;response;Reverse Transcriptase Inhibitors;Selfish Genes;Sequence Homologs;System;Testing;Time;Tissues;Transcriptional Regulation;Transcriptional Silencer Elements;transcriptomics;Variant

PROJECT_TITLE: Dietary impacts on organismal health through altering epigenetic silencing of transposable elements


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Non-activated CAR T cells are a novel platform for T cell-based immunotherapies, generating enhanced potency and accessibility to more patients. We will explore mechanisms to further enhance the potency of non-activated T cells by inhibiting IFN1 which limits transduction and overall functional competence. We will also focus on restoring the expression of viral-associated proteins, and concurrently modulating the IFN1 response in quiescent T cells, to enhance transduction efficiency, which is a critical barrier to the use of these cells.

PI_NAMEs: GHASSEMI, SABA  (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Affect;Antigens;Binding Proteins;Blood;Cancer Model;CAR T cell therapy;cell behavior;Cell Therapy;Cells;Cellular immunotherapy;Characteristics;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;clinically relevant;Competence;Data;Dedications;Endocytosis;Engraftment;exhaustion;Failure;FDA approved;fitness;Gene Delivery;Goals;Hematopoietic Neoplasms;HIV;HIV Infections;Hour;Immune;immune checkpoint;Immune Evasion;Immunotherapy;improved;In Vitro;in vivo;in vivo Model;Individual;Infection;Infrastructure;Infusion procedures;Interferon Type I;Interferons;Investigation;lentivirally transduced;Lentivirus;Lentivirus Vector;leukemia;Malignant Neoplasms;manufacture;manufacturing process;Mediating;Membrane Fusion;Memory;Metabolic;mouse model;novel;Nucleotides;Pathway interactions;Patients;Phenotype;Plasmids;programs;Proteins;Protocols documentation;Research;Resistance;resistance mechanism;response;Rest;Reverse Transcription;Signal Pathway;Signal Transduction;Standardization;stemness;success;synergism;T memory cell;T-Cell Activation;T-Lymphocyte;Therapeutic;therapy resistant;transduction efficiency;Treatment Efficacy;tumor;Tumor Antigens;Tumor Escape;tumor heterogeneity;tumor-immune system interactions;vector;Viral;Virulence Factors;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Increasing the efficacy of non-activated CAR T cells by modulating IFN1 signaling

STUDY_SECTION: TIR

STUDY_SECTION_NAME: Therapeutic Immune Regulation Study Section[TIR]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Neurosciences

ORG_CITY: Columbus

ORG_DEPT: DENTISTRY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The proposed project is relevant to public health because it aims to understand the cues guiding tooth develop- ment, which can be used to develop better preventative and treatment strategies for our dentition. This re- search stands to reveal candidates to test in follow-up tooth regeneration experiments that could help develop new pulp therapies and greatly improve dental healthcare at all stages of life. Thus, the proposed research is relevant to the NIDCR’s mission to improve dental healthcare through research and dissemination of health information.

PI_NAMEs: PETERS, SARAH  (contact)

PROGRAM_OFFICER_NAME: WAN, JASON

PROJECT_TERMS: Adult;Affect;afferent nerve;age related decline;Animals;Apical;Automobile Driving;Award;Axon;axon guidance;Biological Assay;Biomedical Engineering;bone;Cell Culture Techniques;Cells;Chemotactic Factors;Childhood;Clinical;Coculture Techniques;Communication;Complex;conditional knockout;Cues;Data;density;Dental;Dental Pulp;Dentin;Dentists;Dentition;Deposition;design;Development;Developmental Process;Disease;Endodontics;Ensure;Enterobacteria phage P1 Cre recombinase;experimental study;Family;follow-up;Genetic Transcription;Goals;Health;Healthcare;Histology;Human;Image;Immunofluorescence Immunologic;improved;In Situ Hybridization;in vitro Assay;Injury;innovation;Knockout Mice;Knowledge;Label;Length;Life;Maintenance;Mesenchymal;Mesenchyme;mineralization;Mission;Modeling;Molar tooth;Morphology;mouse model;Mus;Natal Teeth;National Institute of Dental and Craniofacial Research;Natural regeneration;Nerve Endings;Nerve Fibers;nerve supply;Neurites;neuron development;Neurons;neurotransmission;neurotrophic factor;neurovascular;Odontoblasts;Oral health;Organ;Penetration;Play;Population;postnatal;precision medicine;preservation;Prevention strategy;Procedures;Process;promoter;Proteins;Public Health;Qualifying;Recombinants;regenerative;Regulation;Reporting;Research;restorative material;Risk;Role;secretion process;Semaphorins;Sensory;Shapes;Signal Transduction;Technology;Testing;Thick;Time;Tissues;tomography;Tooth regeneration;Tooth structure;Transforming Growth Factor beta;Trauma;treatment strategy;Trigeminal System

PROJECT_TITLE: SEMA7a regulation of tooth mineralization, root elongation, and innervation

STUDY_SECTION_NAME: Special Emphasis Panel[ZDE1 JC (11)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: TOLEDO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS

PHR: PROJECT NARRATIVE Changes in kidney health are believed to be common during medical treatment to lower blood pressure because clinicians use an antiquated monitoring approach based on blood creatinine levels. This research proposal will develop and evaluate an improved method for assessing kidney health based on urine proteins that originate within the kidneys. Our goal is to change the paradigm for kidney health monitoring and allow more people to achieve hypertension control and healthier lives.

PI_NAMEs: GUPTA, RAJESH  (contact)

PROGRAM_OFFICER_NAME: VARAGIC, JASMINA

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;Address;adjudication;Adult;Albuminuria;alpha-1-microglobulin;Ancillary Study;Anti-Hypertensive Agents;arm;Arterial Fatty Streak;Benign;biobank;Biological Markers;Biological Specimen Banks;biomarker panel;Blood;Blood Pressure;blood pressure control;blood pressure elevation;blood pressure reduction;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Cardiovascular system;Cessation of life;Clinical;Clinical Data;clinical phenotype;clinical practice;cohort;comparative;Creatinine;Disease;Event;Failure;follow-up;Goals;Health;Heart failure;hemodynamics;high risk;high risk population;Hypertension;hypertension control;hypertension treatment;Impairment;improved;Individual;Injury to Kidney;insight;Interruption;Intervention;Investigation;Kidney;Kidney Failure;kidney vascular structure;Knowledge;Measures;Medical;Methods;Monitor;Morbidity - disease rate;mortality;Myocardial Infarction;Outcome;patient population;patient subsets;Patients;Perception;Persons;Pharmaceutical Preparations;Population;predictive marker;Prevention;Proteins;Randomized;Recommendation;Regimen;renal artery;Renal Artery Stenosis;renal damage;Renal function;Renal tubule structure;Research Proposals;Resistance;Resistant Hypertension;response;Risk;Risk Factors;risk stratification;Serum;Specimen;Stents;Stroke;Structure;Subgroup;System;Testing;tool;Translating;Urine;Work

PROJECT_TITLE: Building a kidney monitoring panel to guide therapy in resistant hypertension

STUDY_SECTION: KEDD

STUDY_SECTION_NAME: Kidney Endocrine and Digestive Disorders Study Section[KEDD]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: NORTH CHICAGO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI

ORG_STATE: IL

PHR: Project Narrative Social behavior is a key element of mammalian function and impairments are a core feature of Autism Spectrum Disorders (ASD). There are known genes that influence social function, and genetic risk factors for ASD, but the influence of these genes on neural circuits of social behavior is mostly unknown. Understanding the impact of these genetic factors on these neural circuits is necessary to uncover how they influence social function.

PI_NAMEs: ROSENKRANZ, JEREMY E (contact)

PROGRAM_OFFICER_NAME: FERNANDEZ, FERNANDO R

PROJECT_TERMS: Acute;Alleles;Amygdaloid structure;Anterior;autism spectrum disorder;autism symptoms;Behavior;Behavioral;behavioral impairment;Brain region;cingulate cortex;Communication;Cues;Electrophysiology (science);Elements;emotional behavior;Equilibrium;experience;Fiber;flexibility;Fluorescence;Genes;Genetic;Genetic Diseases;genetic risk factor;Goals;Health;Heritability;high risk;Impairment;In Vitro;in vivo;Individual;Interneurons;knock-down;Knock-out;knockout gene;Learning;Link;Measures;Mental Health;mortality;motivated behavior;Mutation;neural;neural circuit;Neurobiology;Neurons;novel;Output;pharmacologic;Photometry;physical conditioning;Play;Positioning Attribute;postsynaptic;Prefrontal Cortex;presynaptic;Primates;Proteins;Rattus;Research;response;Risk;risk variant;Rodent;Role;selective expression;small hairpin RNA;social;Social Adjustment;Social Behavior;Social Conditions;social deficits;social engagement;Social Functioning;social influence;Social Interaction;Social Network;social relationships;Sorting;Stimulus;Symptoms;Synapses;synaptic function;Synaptic plasticity;Synaptosomes;Testing;trait;Western Blotting

PROJECT_TITLE: Role of neurexin in social adaptation and amygdala plasticity

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Calcium oxalate kidney stones are a common, recurrent condition (affecting about 10% of the US population) with increasingly prevalence, but preventative treatments are only incompletely effective. Stones are aggregates of calcium oxalate crystals held together by a complex mixture of urinary proteins, though the matrix phase and its role in mechanical strength is poorly understood. The proposed experiments will characterize the protein-protein interactions and their influence on protein-crystal interactions involved in stone formation, so that we can better understand matrix contributions and design better treatments.

PI_NAMEs: TIRRELL, MATTHEW ;WESSON, JEFFREY A (contact)

PROGRAM_OFFICER_NAME: MULLINS, CHRISTOPHER V

PROJECT_TITLE: Protein interactions that control calcium oxalate stone formation

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Heart Disease;Nanotechnology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: NEW YORK

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

ORG_STATE: NY

PHR: PROJECT NARRATIVE Extracellular vesicle (EV) therapy is a promising strategy for tissue regeneration. But the large-scale production of EVs remains a challenge. In the proposed study, we seek to develop a scale-up friendly method to generate a large number of therapeutic nanovesicles (NV) from MSCs by extrusion.

PI_NAMEs: HUANG, KE  (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: adult stem cell;Anatomy;angiogenesis;Animal Model;Animals;Applications Grants;Area;Biological;Biotechnology;bone marrow mesenchymal stem cell;Cardiac;Cardiac Myocytes;cardiac repair;Cells;Clinic;clinical translation;clinically relevant;Communicable Diseases;Conduct Clinical Trials;Data;Development;Dose;Drug Delivery Systems;early phase clinical trial;engineered stem cells;Engineering;exosome;Extracellular Matrix;extracellular vesicles;fabrication;Failure;Fibrosis;Foundations;Friends;Future;gain of function;genetic manipulation;Heart;Heart Injuries;Human;In Vitro;in vivo;Injections;Injury;innovation;Ischemia;ischemic injury;large scale production;loss of function;Mediating;Mediator;Mesenchymal Stem Cells;Methods;mouse model;Mus;Myocardial Infarction;Myocardial Ischemia;Myocardial Reperfusion Injury;Myocardium;nanoparticle;nanosized;nanotoxicity;nanovesicle;Oncology;Organ;Oxidative Stress;paracrine;Pathway interactions;porcine model;Pre-Clinical Model;Process;Production;Proliferating;Proteins;regenerative;Regenerative Medicine;Regimen;repaired;Reperfusion Injury;replacement tissue;RNA;Rodent;Rodent Model;Safety;scale up;Series;small molecule;stem cell genes;stem cells;Surface;Technology;technology platform;Testing;Therapeutic;Therapeutic Effect;therapeutic evaluation;tissue regeneration;tissue repair;Translating;translational clinical trial;treatment response;Vesicle;Work

PROJECT_TITLE: Cell-drones: engineered stem cell nanovesicles as alternatives to exosomes

STUDY_SECTION: INN

STUDY_SECTION_NAME: Innovations in Nanosystems and Nanotechnology Study Section [INN]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: FAYETTEVILLE

ORG_NAME: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE

ORG_STATE: AR

PHR: PROJECT NARRATIVE This project will investigate the ecological and epidemiological dynamics underpinning emerging bat-borne viruses and how risks are altered by human activities. We will focus on three important and tractable host-virus systems: coronaviruses, rabies lyssavirus, and Bombali ebolavirus, in their wild bat hosts in the Taita Hills, Kenya and Orange Walk, Belize. This research will represent an unusually comprehensive and detailed investigation into the dynamics of viruses in wild bat populations and provide a critical advance towards evidence-based risk prevention.

PI_NAMEs: FORBES, KRISTIAN MICHAEL (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: 2019-nCoV;Address;Affect;Agriculture;Animals;anthropogenesis;Area;Automobile Driving;bat-borne;Behavior;behavioral study;Belize;biological adaptation to stress;Chiroptera;Church;Communities;comparative;Coronavirus;COVID-19;COVID-19 pandemic;Data;design;detection platform;diagnostic assay;disorder risk;Domestic Animals;Ebola virus;Emerging Communicable Diseases;emerging virus;epidemiological model;Epidemiology;Evaluation;Event;evidence base;experimental study;exposed human population;Exposure to;Frustration;global health;Habitats;Health;high risk;Human;Human Activities;human disease;Immune response;Immunity;Individual;Infection;interdisciplinary approach;Intervention;Investigation;Kenya;Livestock;Low income;Lyssavirus;Maps;mathematical model;Measures;Metagenomics;Modeling;Monitor;Movement;neglect;Oranges;Parameter Estimation;pathogen spillover;Pattern;Policies;Population;Prevalence;prevent;Prevention;Process;Proteomics;Rabies virus;Research;response;Risk;Risk Assessment;Rural;Sampling;Schools;Seasons;Security;Serology;Severe Acute Respiratory Syndrome;Shapes;simulation;Site;Social Marketing;Stress;Structure;Surveys;System;Testing;Time;transmission process;Viral;viral transmission;Virus;Virus Diseases;Virus Latency;Virus Shedding;Walking;Zoonoses

PROJECT_TITLE: Beyond discovery: bat behavior and virus shedding as drivers of spillover risk

STUDY_SECTION: TVZ

STUDY_SECTION_NAME: Transmission of Vector-Borne and Zoonotic Diseases Study Section [TVZ]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Chronic Pain;Neurosciences;Pain Research;Physical Injury - Accidents and Adverse Effects;Wound Healing and Care

ORG_CITY: CORAL GABLES

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE In burn injuries, healing wounds and managing the associated itch and pain are critical but often not addressed sufficiently. Our project aims to explore how Langerhans cells and sensory neurons interact and impact wound healing, itch, and pain following burn injuries. By understanding these interactions, we hope to uncover new insights into Langerhans cell functions and develop innovative therapeutic strategy for burn injuries.

PI_NAMEs: AKIYAMA, TASUKU  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acute;Affect;Afferent Neurons;Animal Model;Behavior;behavioral response;Bone Marrow;Burn injury;burn wound;Calcium;candidate identification;candidate marker;Cations;Cell Communication;Cell Physiology;Chimera organism;Chronology;Comprehension;Data;designer receptors exclusively activated by designer drugs;Epidermis;Esthesia;Exhibits;Free Nerve Ending;Genetic;Goals;healing;Healthcare;Hematopoietic;Image;improved;In Vitro;in vitro activity;in vivo;Individual;innovation;insight;Knowledge;Langerhans cell;Light;Measures;Mediating;Medical;Methods;Modeling;Molecular;Monitor;monocyte;mouse model;Mus;Nerve;Neurons;Nociception;Nociceptive Stimulus;novel strategies;novel therapeutic intervention;optogenetics;Pain;Patients;Play;Population;Population Heterogeneity;Process;Property;Pruritus;Psychological Stress;Publishing;Quality of life;recruit;reinnervation;response;Role;Sampling;selective expression;single-cell RNA sequencing;Skin;Testing;Therapeutic;tool;Transgenic Mice;United States;wound;wound care;wound healing;wound treatment

PROJECT_TITLE: Interplay Between Langerhans Cells and Sensory Neurons: Impact on Wound Healing and Nociception Following Burn Injuries

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


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;Clinical Research;Dementia;Mental Health;Neurodegenerative;Neurosciences

ORG_CITY: DURHAM

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative Strong attentional control can protect cognitive function when the brain is injured and inflamed, which makes attentional control a potentially powerful tool for reducing the incidence and impact of delirium and dementia. This work will explore neural mechanisms behind attentional resilience—the ability to maintain strong attentional control despite physiological stressors—using the natural experiment of scheduled surgery in cognitively intact older adults. By studying neural mechanisms that allow for robust attentional control capacity before surgery and attentional resilience after surgery, we expect to identify mechanistic targets which may inform future interventions to protect cognition in older adults at risk for delirium and dementia.

PI_NAMEs: ACKER, LEAH  (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acute;Age;Aging;Alzheimer associated neurodegeneration;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;Attention;attentional control;Attentional deficit;attenuation;Biological Markers;biomarker panel;Blood;Brain;Chronic;Chronic stress;Clinical;Cognition;Cognitive;cognitive function;cognitive performance;cognitive task;cognitive testing;Compensation;confusion assessment method;Darkness;Data;Delirium;Dementia;directed attention;Dorsal;Electroencephalography;Environment;Evaluation;Event-Related Potentials;executive function;experience;Eye;Functional Magnetic Resonance Imaging;Future;Goals;Head;Impaired cognition;inattention;Incidence;Individual;Inflammation;injured;Injury;insight;Intervention;Link;Measurement;Measures;Mediating;Mediator;Natural experiment;nerve injury;neural;neural circuit;Neural Pathways;neuroinflammation;neuromechanism;Neuronal Injury;Neurons;neuroregulation;older adult;Operative Surgical Procedures;Outcome;Pathology;Patients;Pattern;Performance;performance tests;physiologic stressor;Postoperative Period;pre-clinical;preservation;Process;resilience;resilience in aging;Resources;response;Rest;Risk;Risk Factors;Schedule;Sensory;sensory stimulus;sex;Stimulus;Stress;stressor;System;tau Proteins;Testing;therapy development;tool;Visual;visual stimulus;Work

PROJECT_TITLE: Attentional Resilience in Older Adults

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-W (02)]


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

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: Project Narrative: Despite significant improvements in treatment-adapted strategies, over 70% of acute myeloid leukemia (AML) patients cannot be cured with contemporary therapies, underscoring the unmet medical need to identify new therapeutic target(s) and develop improved strategies. This proposal aims to investigate the role of METTL1, an enzyme responsible for tRNA 7-methylguanosine (m7G) modification, in AML pathogenesis and leukemia stem cell homeostasis, and explore the underlying molecular mechanism(s). Additionally, we have identified a potent and selection small molecule inhibitor of METTL1 and will assess its therapeutic potential, either alone or in combination with other therapeutic agents, for the treatment of high-risk AMLs.

PI_NAMEs: SU, RUI  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: 7-methylguanosine;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Attenuated;Automobile Driving;Biological;Biological Assay;Biological Process;Bone Marrow;Bone Marrow Transplantation;cancer cell;cell growth;Cells;Chemicals;chemokine;chemokine receptor;Chemoresistance;Chemotherapy-Oncologic Procedure;Clinical;Clonal Expansion;Codon Nucleotides;conditional knockout;conventional therapy;Coupled;CRISPR screen;CXC Chemokines;Data;Deposition;Development;DNMT3a;DNMT3a mutation;druggable target;Enzymes;Evaluation;FLT3 gene;Frequencies;Genetic;genome-wide analysis;Growth;Hematopoietic;Hematopoietic Neoplasms;high risk;high throughput screening;Homing;improved;In Vitro;in vivo;infancy;inhibitor;insight;Investigation;Knock-in Mouse;Knockout Mice;leukemia;leukemia treatment;leukemic stem cell;leukemogenesis;Ligands;loss of function;Maintenance;Medical;Methyltransferase;MLL-AF9;MLL-rearranged leukemia;Modeling;Modification;Molecular;mouse model;mRNA Translation;mutant;new therapeutic target;Newly Diagnosed;NPM1 gene;Oncogenic;Outcome;overexpression;Pathogenesis;Pathologic;Pathway interactions;patient derived xenograft model;Patients;pharmacologic;Post-Transcriptional Regulation;Prognosis;Protein Tyrosine Kinase;Proteins;Relapse;Resistance;RNA;Role;self-renewal;Signal Transduction;small molecule inhibitor;Specimen;stem cell homeostasis;stem cell self renewal;targeted treatment;Therapeutic;Therapeutic Agents;therapy development;Transcript;Transfer RNA;Transgenic Organisms;Translations;Treatment Efficacy

PROJECT_TITLE: The role, mechanism, and therapeutic potential of METTL1 in acute myeloid leukemia

STUDY_SECTION: BCO

STUDY_SECTION_NAME: Biochemical and Cellular Oncogenesis Study Section[BCO]


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Lung Cancer;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: NEW ORLEANS

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: LSU HEALTH SCIENCES CENTER

ORG_STATE: LA

PHR: PROJECT NARRATIVE African Americans have both the highest incidence and mortality of lung cancer compared to any other racial/ethnic group. To address this urgent public health concern, this study aims to reduce disparities and the burden of lung cancer among AA smokers by supporting a Multiple-level intervention integrating lung cancer screening and smoking cessation{MILS), followed the NIH DEIA strategies using multilevel interventions that impact determinants of health and address health disparities at appropriate time points across the life course. The results of the study will directly guide the development of targeted strategies to improve lung cancer screening rates among minorities.

PI_NAMEs: TSENG, TUNG SUNG  (contact)

PROGRAM_OFFICER_NAME: BARKSDALE, CRYSTAL

PROJECT_TERMS: Academic Medical Centers;Address;Adherence;Adult;African American;African American population;Aftercare;Age;American Cancer Society;Attitude;Behavior;Biochemical;Cessation of life;Clinical Trials;Communities;Community Health Aides;compare effectiveness;computed tomography screening;Control Groups;Data;design;Development;Disparity;disparity reduction;Education;Effectiveness;Eligibility Determination;ethnic diversity;ethnic minority;Ethnic Population;experience;Focus Groups;follow-up;Frequencies;gender difference;Goals;group intervention;Guidelines;health determinants;health disparity;high risk;high risk population;improved;Incidence;Individual;informant;Institution;Intervention;Interview;Knowledge;Life Cycle Stages;Light;Louisiana;low dose computed tomography;lung cancer screening;Malignant neoplasm of lung;Methods;Minority;mortality;Nicotine Dependence;Pattern;Population;Population Heterogeneity;Prevalence;prevent;Preventive screening;primary outcome;Program Sustainability;Provider;Public Health;racial difference;racial diversity;racial minority;racial population;Recommendation;Recording of previous events;Reduce health disparities;Research;screening;screening guidelines;Services;Smoker;Smoking;Smoking Behavior;smoking cessation;Smoking Cessation Intervention;Smoking History;Surveys;synergism;Testing;Time;tobacco abstinence;Tobacco use;Tobacco Use Cessation;treatment as usual;United States National Institutes of Health;United States Preventative Services Task Force;uptake

PROJECT_TITLE: Effectiveness of a multilevel integrated intervention for LDCT lung cancer screening and smoking cessation among African Americans

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IVBH-G (55)]


ORG_CITY: EVANSTON

ORG_NAME: ENDEAVOR HEALTH CLINICAL OPERATIONS

PHR: NARRATIVE  The role of macrophages as mediators of energy transfer during local invasion of prostate cancer is unclear. Macrophages may play a key role in energy transfer to tumor epithelial cells and can promote growth and invasion. The pathways involved in this process are targetable and represent a novel area for therapy in locally invasive disease.

PI_NAMEs: HAYWARD, SIMON W (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Ablation;absorption;Acceleration;Adipocytes;adipokines;Adipose tissue;Anatomy;Androgen Receptor;Area;ATP binding cassette transporter 1;biobank;Blood Vessels;capsule;CD36 gene;Cells;Cessation of life;Characteristics;chemokine;Clinic;cytokine;Data;Development;diacylglycerol O-acyltransferase;Disease;Energy Transfer;Energy-Generating Resources;Environment;Epithelial Cells;Evaluation;Extracapsular;extracellular;FABP5 gene;Fatty acid glycerol esters;fatty acid-binding proteins;Fibroblasts;Growth;Heterogeneity;Histologic;Human;human tissue;Immunofluorescence Immunologic;In Vitro;in vitro Model;in vivo;Infiltration;Inflammatory;inhibitor;Interleukin-1 beta;Interleukin-6;Invaded;Investigation;lipid mediator;Lipids;Macrophage;Malignant neoplasm of prostate;Malignant Neoplasms;Mammary Neoplasms;Mediator;Metabolic;Mus;neoplastic cell;NF-kappa B;novel;NRIP1 gene;Nutrient;Nutrient availability;Organ;Organoids;overexpression;Pathway interactions;Penetration;perilipin;Periprostatic;Peroxisome Proliferator-Activated Receptors;pharmacologic;Phenotype;Play;Population;pre-clinical;Process;Proliferating;Prostate;Prostate Cancer therapy;Prostatic;Prostatic Neoplasms;Proteins;Regulation;Reporting;response;Risk;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;small molecule inhibitor;Source;targeted treatment;Testing;Therapeutic;therapeutically effective;Tissue Recombination;Tissues;TNF gene;translational potential;tumor;Tumor Biology;Tumor Cell Invasion;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;Tumor-associated macrophages;tumorigenic;Visceral fat;Xenograft Model

PROJECT_TITLE: Lipid-Rich Macrophages at the Tumor-Adipose Interface:  A New Target for Locally-Invasive Prostate Cancer Therapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-2 (M3)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: NARRATIVE Aicardi Goutières syndrome (AGS) is a progressive, autoinflammatory encephalopathy caused by genetic mutations in nucleic acid sensing and processing machinery that leads to overproduction of type I interferon. How systemic IFN production leads to predominant neuropathology is unknown but is imperative to understand for therapy development. This proposal uses mouse models of AGS that recapitulate neuropathology, paired with new gene and cell targeting approaches to uncover the cells, which drive pathology in order to facilitate therapy development.

PI_NAMEs: BENNETT, MARIKO L. (contact);VANDERVER, ADELINE LUCIE;WANG, QINGDE

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Acceleration;Address;Advocacy;Affect;Astrocytes;autoinflammatory;autoinflammatory diseases;Automobile Driving;Behavior;Biological Models;Blood - brain barrier anatomy;Blood Vessels;Bone Marrow;Brain;brain cell;calcification;cell type;Cells;cellular targeting;Central Nervous System;central nervous system injury;Cerebrospinal Fluid;cerebrovascular;Clinical;clinical translation;cognitive disability;combinatorial;CXCL10 gene;cytokine;Development;Disease;DNA Sequence Alteration;Double-Stranded RNA;dsRNA adenosine deaminase;effective therapy;Encephalopathies;Endothelial Cells;Endothelium;Enzymes;experience;experimental study;Gene Expression;Gene Modified;gene therapy;Genes;Genetic;Genetic Transcription;Genotype;Hematopoietic Stem Cell Transplantation;Hepatitis;Histopathology;Human Genetics;Human Pathology;IFIH1;Immune;Immune system;Immunophenotyping;Inflammatory;inhibitor;Injury;Innate Immune Response;insight;Interferon Type I;Interferons;Janus kinase;kinase inhibitor;knock-down;Knowledge;Laboratories;Lead;leukodystrophy;Lymphocyte;Lymphocytosis;Macrophage Colony-Stimulating Factor Receptor;Mature Lymphocyte;Measures;Mediating;Microglia;Modeling;mouse model;Mus;Mutation;Myelogenous;Nature;neurological pathology;Neurons;neuropathology;neurovascular unit;novel;Nucleic Acids;Oligodendroglia;Outcome;overexpression;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Pediatric Hospitals;Pericytes;Peripheral;Peripheral Nervous System;Pharmaceutical Preparations;Phenocopy;Philadelphia;physically handicapped;Population;Production;programs;pseudotoxoplasmosis syndrome;Research Personnel;Resistance;RNA Editing;Rodent Model;Role;Signal Transduction;skin lesion;System;systemic inflammatory response;targeted treatment;Testing;theories;Therapeutic;therapeutic development;therapeutic RNA;Therapeutic Uses;therapy development;Time;tool;transcriptomics;Translating;Transplantation;Universities;Vascular Diseases;vascular endothelial dysfunction;Vascular Endothelium;vascular injury;Viral;Work

PROJECT_TITLE: Interactions between diverse brain cell types drive Aicardi-Goutieres neuropathology

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF OPTOMETRY/OPHT TECH

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Estrogen;Eye Disease and Disorders of Vision;Genetics;Menopause;Women's Health Research

ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: Three-quarters of patients with Fuchs Corneal Endothelial Dystrophy, a blinding eye disease, are postmenopausal women. The goal of this project is to determine if estrogen protects corneal endothelial cells. Completion will answer this basic question and could lead to new therapies for this eye disease.

PI_NAMEs: BONANNO, JOSEPH AURELIO (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Acceleration;Acute;Affect;Age;Age related macular degeneration;Agonist;Antioxidants;Apoptosis;Basement membrane;biological sex;bone;Cardiovascular Diseases;Cardiovascular system;Cataract;Cell Density;Cellular Morphology;Cornea;Corneal edema;Corneal Endothelium;Cultured Cells;density;Deposition;Development;DNA;DNA Adducts;Dry Eye Syndromes;Endothelial Cells;endothelial dysfunction;Endothelium;Estrogen decline;Estrogen Receptors;Estrogen Replacement Therapy;estrogenic;Estrogens;Eye diseases;eye dryness;Eyedrops;Female;Fuchs' Endothelial Dystrophy;Functional disorder;Gene Expression;Genes;Genetic;Glaucoma;Goals;Gonadal Steroid Hormones;Health;human model;Incidence;Introns;Knock-out;Knockout Mice;Life;Lipids;Macular degeneration;male;Measures;men;Menopause;Metabolic;Methods;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Modeling;Morphology;mouse model;Mus;Mutant Strains Mice;Mutation;novel therapeutics;Nuclear;older women;Osteoporosis;oxidation;oxidative damage;Oxidative Stress;Oxygen Consumption;Pathway interactions;Patients;Phenotype;Physiology;Population;Postmenopause;Premenopause;Prevalence;protective effect;Proteins;Reactive Oxygen Species;Retinal Ganglion Cells;Rodent Model;Severities;sex;SOD2 gene;Specimen;TCF7L2 gene;Testing;Thick;Time;Tissues;Transgenic Organisms;Ultraviolet Rays;Vasodilation;Woman;women patients

PROJECT_TITLE: Modulation of Corneal Endothelial Mitochondrial Activity and Dysfunction by Estrogen

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Genetics;Lung;Rare Diseases

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: Project Narrative Acute lung injury (ALI) is a clinical syndrome of acute respiratory failure with high morbidity and mortality, and is associated with an uncontrolled inflammatory response due to excessive production of cytokines and other inflammatory mediators. We recently discovered a significant upregulation of specific tRNA- and rRNA-derived short non-coding RNAs (sncRNAs) in a Lipopolysaccharide-induced ALI model. Our project aims to comprehensively investigate the dysregulation of these sncRNAs in human and mouse ALI models and to elucidate their role in cytokine overproduction and immune cell infiltration, thus contributing to a deeper understanding of the molecular pathogenesis of ALI.

PI_NAMEs: DESHPANDE, DEEPAK A;KIRINO, YOHEI  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA GRANDON, INGRID CECILIA

PROJECT_TERMS: Acute Lung Injury;Acute respiratory failure;alveolar epithelium;angiogenin;Biogenesis;Biological Markers;Biological Process;Biology;Bronchoalveolar Lavage;cell motility;Cells;Chemotaxis;Clinical;cytokine;cytokine release syndrome;Data;effective therapy;Endoribonucleases;Endosomes;Enzyme-Linked Immunosorbent Assay;Epithelial Cells;Etiology;extracellular vesicles;Focal Adhesions;Future;Human;human disease;human model;Hydroxyl Radical;Immune;immune cell infiltrate;Infiltration;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;inorganic phosphate;insight;Investigation;Kinetics;Knowledge;Link;Lipopolysaccharides;Literature;Lung;Macrophage;Malignant Neoplasms;Methods;MicroRNAs;migration;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;Mus;Nerve Degeneration;neutrophil;Neutrophil Infiltration;novel;Pancreatic ribonuclease;Pathogenesis;Pathologic;Pathway interactions;Periodicity;Phosphorylation;Plasma;Play;potential biomarker;prevent;Process;Production;Protein Tyrosine Kinase;Pulmonary Inflammation;Research;respiratory;Ribosomal RNA;RNA;RNA delivery;Role;Slice;Structure of parenchyma of lung;Subgroup;success;Syndrome;System;Techniques;Therapeutic;therapeutic target;TLR7 gene;TLR8 gene;Toll-like receptors;tool;transcriptome sequencing;Transfer RNA;Untranslated RNA;Up-Regulation

PROJECT_TITLE: Role of tRNA- and rRNA-derived RNAs in acute lung injury

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

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

ORG_CITY: BERKELEY

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: NARRATIVE: Obesity is associated with increased risk of metabolic disorders including fatty liver disease, but the mechanisms underlying this connection are not fully understood. Work from our lab and others has demonstrated that in the liver, obesity is associated with striking changes in sub-cellular architecture, particularly of the endoplasmic reticulum (ER) and its interaction with other organelles. Here, we will investigate the relationship between ER structure and function in metabolic regulation and disease, which we anticipate will reveal novel strategies to treat metabolic-associated fatty liver disease.

PI_NAMEs: ARRUDA, ANA PAULA  (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Affect;Architecture;Binding Proteins;Biochemical;Cells;chronic liver disease;Data;Deterioration;Development;Diet;diet-induced obesity;Dimensions;Disease;Endoplasmic Reticulum;Equilibrium;Event;Fasting;fatty acid oxidation;Fatty Liver;fatty liver disease;flexibility;fluorescence imaging;Functional disorder;gain of function;Genetic;Goals;Health;Hepatic;Hepatocyte;Homeostasis;Human;human tissue;Image;Impairment;improved;in vivo;Incidence;Integral Membrane Protein;ketogenesis;Label;Lead;lipid metabolism;Lipids;Liver;liver metabolism;loss of function;Machine Learning;Membrane;Metabolic;Metabolic Diseases;Metabolic dysfunction;metabolic phenotype;Metabolic stress;metabolic-associated fatty liver disease;Mitochondria;mouse model;mRNA Translation;Mus;Mutation Analysis;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Nutritional;Obese Mice;Obesity;obesity genetics;obesity treatment;Organelles;Outcome;Output;overexpression;Overnutrition;Pathogenesis;Physiological;Play;Process;programs;Protein Biosynthesis;protein metabolism;Protein Overexpression;receptor binding;Receptor Down-Regulation;receptor downregulation;Regulation;Resolution;response;Ribosomal Proteins;Risk;Role;Rough endoplasmic reticulum;Site;Societies;Stress;Structure;Testing;Tissues;Work

PROJECT_TITLE: The role of hepatic Endoplasmic Reticulum architecture in metabolic homeostasis and disease

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


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

ORG_CITY: ATLANTA

ORG_DEPT: PEDIATRICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: The proposed research is relevant to public health because it addresses a critical unmet medical need for patients with liver disease and associated kidney injury. The studies in this proposal will provide key and potentially paradigm-changing insights to the role of kidney and biliary tract bile acid transport in the development of those disorders. The studies are predicted to have a therapeutically significant impact on the development of medical therapies for patients suffering from cholestatic liver diseases such as Primary Biliary Cholangitis, Progressive Familial Intrahepatic Cholestasis, and Alagille Syndrome.

PI_NAMEs: DAWSON, PAUL A (contact)

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: absorption;Acids;Address;Alagille Syndrome;ASBT protein;bile acid transporter;Bile Acids;bile duct;Bile fluid;Biliary;biliary tract;Cells;Childhood;cholangiocyte;Cholestasis;Cytoprotection;cytotoxic;Data;design;Development;Disease;effective therapy;Enterocytes;Epithelial Cells;epithelial injury;Epithelium;Excretory function;Functional disorder;Genetic Models;Goals;Hepatic;Hepatobiliary;hepatoprotective;Human;Hydrophobicity;ileum;imaging approach;inhibitor;Injury to Kidney;innovation;insight;interest;intravital imaging;Kidney;Kidney Diseases;Knock-out;Knockout Mice;Ligation;Liver;Liver diseases;liver injury;Mediating;Medical;Modeling;Molecular;mouse model;multiorgan damage;Mus;nephrotoxicity;novel;Oral;Organ;Organoids;Pathogenesis;patient subsets;Patients;pharmacologic;Physiological;prevent;Primary biliary cirrhosis;Progressive intrahepatic cholestasis;Proximal Kidney Tubules;Public Health;Publishing;Renal tubule structure;Research;Role;success;Surgical Models;Testing;Therapeutic;Time;Tissues;Toxic effect;Translating;uptake;urinary;Urine;Work

PROJECT_TITLE: Hepatoprotective Mechanisms of Systemic Bile Acid Transporter Inhibitors


NIH_SPENDING_CATS: Cancer;Cannabinoid Research;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Dietary Supplements;Digestive Diseases;Health Disparities and Racial or Ethnic Minority Health Research;Microbiome;Natural Products;Nutrition;Obesity;Pediatric;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Epidemiological studies have found a strong link between obesity and colorectal cancer and experimental studies in mice substantiate these claims. Based on our convincing preliminary data that shows that the cannabis plant can reduce inflammation and metabolic dysregulation – factors that are associated with driving tumorigenesis - we will test the hypothesis that the cannabis plant can reduce meta-inflammation and subsequent metabolic dysfunction in obesity-associated colorectal cancer. This work will provide Chrisitan with extensive training in mouse models of cancer, in immune profiling, and in assessing microbiome and metabolite signatures, as well as career development that will provide a platform for Christian to launch his independent career focused on metabolic dysregulation and cancer risk.

PI_NAMEs: HOFSETH, LORNE J;MURPHY, ELIZABETH ANGELA (contact)

PROGRAM_OFFICER_NAME: RISCUTA, GABRIELA

PROJECT_TERMS: adenoma;Adipocytes;adiponectin;Adipose tissue;Adult;Advisory Committees;African American;American;Anti-Inflammatory Agents;Antiinflammatory Effect;Attention;Automobile Driving;Award;Bacteria;Biological Assay;Body Weight;C-reactive protein;Cancer Model;cancer risk;Cannabinoids;Cannabis;cannabis administration;career;career development;Cells;Child;Chronic;Colorectal Cancer;colorectal cancer progression;colorectal cancer risk;Communication;Complement 2;Consumption;cytokine;Data;Development;Diet;diet and cancer;dietary;Dietary Intervention;dietary supplements;Enrollment;epidemiology study;European;experimental study;fecal transplantation;Funding;Goals;gut microbes;gut microbiome;gut microbiota;Health Benefit;High Fat Diet;high risk;Homeostasis;Immune;improved;in vivo;Inflammation;Inflammation Mediators;Inflammatory;Influentials;Insulin;Insulin Resistance;Insulin-Like Growth Factor I;Interleukin-6;Intervention;Intervention Trial;intestinal barrier;Link;Macrophage;Malignant Neoplasms;Mediating;Mediator;Mentors;Metabolic;Metabolic dysfunction;microbiome;microbiome signature;microbiota;Modeling;mouse model;Mus;Natural Products;Obese Mice;Obesity;Obesity associated cancer;Outcome;Paper;parent grant;Parents;Pathogenesis;Plants;pre-clinical;protective effect;protective factors;Publishing;Race;racial difference;racial identity;Research Personnel;Research Support;Resources;response;Risk;Risk Assessment;Somatomedins;South Carolina;Study models;System;systemic inflammatory response;Techniques;Testing;TNF gene;Training;tumorigenesis;Unhealthy Diet;Universities;Work

PROJECT_TITLE: A Transdisciplinary Approach to Investigating Metabolic Dysregulation in Obese Parent and Child Dyads and Risk of Colorectal Cancer - admin supplement


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: LOS ANGELES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE We propose to develop new genomic methods for mapping the interactions of proteins and snRNPs to pre- mRNA that are essential to gene function and are often disrupted by mutations causing human disease. An important goal in medical genetics is to identify deleterious sequence variants in patient genomes, but it is currently difficult to predict the effects of many mutations on splicing. By identifying all the binding sites for the U1 snRNP, the LASR complex, and U2AF, we will be able better recognize pathogenic mutations in patients.

PI_NAMEs: BLACK, DOUGLAS L (contact)

PROGRAM_OFFICER_NAME: CHADWICK, LISA

PROJECT_TERMS: 3' Splice Site;5' Splice Site;Affect;Alternative Splicing;Binding;Binding Sites;Cell Fraction;Cells;Chromatin;Code;Complement;Complex;crosslink;Data;Data Analyses;Dependence;Detection;disease model;Elements;Epitopes;Event;Exons;Frequencies;Funding;gene function;Genetic;genetic regulatory protein;Genome;genome-wide;Genomics;Goals;Heterogeneous-Nuclear Ribonucleoprotein Group M;hnRNP-H;Human;human disease;improved;in vivo;Individual;insight;Introns;Maps;Medical Genetics;Methods;Molecular Analysis;mRNA Precursor;Mutation;novel;Pathogenicity;Patients;Phenotype;Polyadenylation;premature;Process;protein complex;protein function;Proteins;Reaction;RNA;RNA Splicing;Role;Site;Small Nuclear Ribonucleoproteins;Spliceosome Assembly Pathway;Spliceosomes;System;tool;Transcript;Transcriptional Silencer Elements;transcriptome;U1 Small Nuclear Ribonucleoprotein;U2 Small Nuclear Ribonucleoprotein;Variant;Work

PROJECT_TITLE: Comprehensive Maps of Early Spliceosome and Regulator Binding to Nascent RNA in Human Cells

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


NIH_SPENDING_CATS: Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Diffuse midline gliomas (DMGs) are deadly brain tumors in children. Our studies have identified a unique combination of metabolic vulnerabilities that can be exploited for therapy and for visualizing early response to therapy in DMGs. Clinical translation of our studies has the potential to improve outcomes and quality of life for children with this pernicious form of cancer.

PI_NAMEs: VISWANATH, PAVITHRA  (contact)

PROGRAM_OFFICER_NAME: TANDON, PUSHPA

PROJECT_TERMS: Address;anatomic imaging;Animals;Apoptosis;Benchmarking;Biopsy;Brain;Brain Neoplasms;Cell Line;Cells;Child;Childhood;Clinical;clinical care;Clinical Research;clinical translation;Clinical Trials;Combined Modality Therapy;Data;Defense Mechanisms;Deuterium;Diagnosis;diffuse midline glioma;disorder control;DNA;Doxycycline;Drug Metabolic Detoxication;Enzymes;Epigenetic Process;Foundations;Gene Expression;Genetic Transcription;Glucose;glucose metabolism;glucose monitor;Glucosephosphate Dehydrogenase;Glutathione;glycation;Glycolysis;Goals;Growth;H3 K27M mutation;Histone H3;Histones;Hyperactivity;Image;Image Enhancement;imaging modality;improved;improved outcome;In Vitro;in vivo;Induction of Apoptosis;inhibitor;innovation;inorganic phosphate;Intracranial Neoplasms;Lactoylglutathione Lyase;Lysine;Magnetic Resonance Imaging;Malignant Childhood Neoplasm;Malignant Neoplasms;Measures;Medicine;Metabolic;metabolic imaging;Metabolism;Methionine;Methods;Methylation;Modeling;Molecular;Mus;Mutation;NADP;Natural regeneration;Nature;neuro-oncology;non-invasive imaging;novel;Nucleotide Biosynthesis;nucleotide metabolism;Nucleotides;Oncogenes;Oncogenic;Outcome;patient prognosis;Patients;Pediatric Neoplasm;Penetrance;Pentosephosphate Pathway;Pharmaceutical Preparations;pharmacologic;Phosphoglycerate Kinase;pre-clinical;Precision therapeutics;preclinical study;Primary Brain Neoplasms;Production;programs;Proliferating;promoter;Proteins;Pyruvaldehyde;Quality of life;Radiation;recruit;Recurrence;Reporting;response;response biomarker;Ribose;Safety;small hairpin RNA;standard of care;synergism;Testing;Therapeutic;therapeutic target;Time;treatment response;tumor;tumor growth;Visualization;Waste Products

PROJECT_TITLE: Combination metabolic therapy for diffuse midline glioma

STUDY_SECTION: ATA

STUDY_SECTION_NAME:
Advancing Therapeutics A Study Section
[ATA]


NIH_SPENDING_CATS: Diabetes;Nutrition

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative  Primary cilia have emerged as key mediators of β-cell function and are associated with the development of diabetes. The purpose of this application is to identify the molecular drivers of ciliary nutrient sensing and signaling, which are currently unknown. Completing the studies outlined in this proposal the potential to discover new cilia-based therapeutic approaches to decrease the burden of diabetes in the United States.

PI_NAMEs: HUGHES, JING WANG (contact);MERRINS, MATTHEW J.

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Address;Beta Cell;Bioenergetics;Biosensor;Cell Physiology;Cells;Cilia;Clinical;Communication;Coupling;Cues;Cyclic AMP;Cytosol;Data;Defect;design;detection of nutrient;Development;Diabetes Mellitus;Diet;Electrophysiology (science);Endocrine;Environment;environmental change;Enzymes;Eukaryotic Cell;Event;extracellular;Functional Imaging;Generations;Genetic;Genetic Models;genome wide association study;Glucose;Glucose Intolerance;glucose metabolism;glucose transport;Glucose Transporter;GLUT-2 protein;Glycolysis;Homeostasis;Human;Human Genetics;imaging approach;improved;innovation;insulin secretion;interdisciplinary approach;Investigation;islet;Islets of Langerhans;Knockout Mice;Knowledge;Label;live cell imaging;loss of function;Mammalian Cell;Mediating;Mediator;Membrane;Membrane Proteins;Metabolic;Metabolic Diseases;Metabolism;metabolome;metabolomics;Microscopy;Microtubules;Mitochondria;Modeling;Molecular;Monitor;Motility;mouse model;Mus;Neurosecretory Systems;novel therapeutics;Nutrient;Obesity;Organelles;Pathway interactions;Phosphoenolpyruvate;Production;Property;protein transport;Proteins;Proteome;Proteomics;rapid detection;Regulation;Research;response;Rodent;Role;Second Messenger Systems;sensor;Signal Pathway;Signal Transduction;Source;Stimulus;Surface;System;Testing;Therapeutic;therapeutic target;tool;United States

PROJECT_TITLE: Metabolic signaling of the beta cell primary cilium

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


PHR: NARRATIVE Sepsis is a leading cause of in-hospital mortality and involves a heterogeneous and dysregulated host immune response to infection. This proposal seeks to advance our understanding and management of sepsis by profiling the immune response and detecting microbial pathogens in blood samples from 1,563 patients enrolled in the multicenter CLOVERS trial, using a technique called metagenomic sequencing. Together, this work will achieve the following specific aims: 1) understand the microbial causes of sepsis, 2) identify subgroups of sepsis patients with distinct immunologic and microbiologic characteristics that may be uniquely treatment-responsive, and 3) develop a novel molecular blood test to accurately predict sepsis outcomes.

PI_NAMEs: LANGELIER, CHARLES  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: 2019-nCoV;Acceleration;Accident and Emergency department;Acute Respiratory Distress Syndrome;Address;adjudication;Antibiotics;Automobile Driving;Biologic Characteristic;Biological;Biological Markers;Blood;Blood specimen;Blood Tests;Candida auris;Caring;Cause of Death;Cessation of life;Clinical;Clinical Data;Clinical Trials;Cluster Analysis;cohort;Complex;Critical Care;Critical Illness;crystalloid;Culture-independent methods;Data;Data Set;Death Rate;Detection;Development;Diagnostic;Disease;effective therapy;emerging pathogen;emerging virus;Enrollment;Etiology;Failure;Functional disorder;Gene Expression;Goals;Heterogeneity;Hospital Mortality;Hospitalization;Hospitals;Hour;Immune response;Immunologics;Immunomodulators;improved;Individual;individualized medicine;Infection;Inflammatory;Inflammatory Response;Intervention;Life;Machine Learning;Measurement;Medical center;metagenomic sequencing;Metagenomics;Methods;Microbe;microbial;Molecular;molecular phenotype;mortality;multiple omics;National Heart, Lung, and Blood Institute;novel;Organism;Outcome;outcome prediction;participant enrollment;pathogen;Pathogenesis;pathogenic microbe;patient population;patient subsets;Patient-Focused Outcomes;Patients;Phenotype;Plasma;precision medicine;Prognosis;prognostic;prognostic tool;Protein Analysis;protein biomarkers;Randomized;Resource Allocation;Resuscitation;risk stratification;Role;Sampling;Sepsis;septic patients;Septic Shock;Shock;Specimen;Subgroup;surveillance study;Taxonomy;Techniques;Testing;Therapeutic;tool;trait;transcriptomics;treatment response;treatment strategy;Triage;United States;unsupervised clustering;Vasoconstrictor Agents;Whole Blood;Work

PROJECT_TITLE: Integrated Host-Microbe Metagenomics for Sepsis Pathogen Surveillance, Subphenotyping and Outcome Prediction

STUDY_SECTION: EDIT

STUDY_SECTION_NAME: Etiology, Diagnostic, Intervention and Treatment of Infectious Diseases Study Section[EDIT]


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

ORG_DEPT: PSYCHOLOGY

PHR: Project Narrative Many neuropsychiatric disorders are accompanied by inflexible decision making. We outline a plan to uncover cortical representations of value that underpin flexible behavior using naturalistically-sensitive behavioral tasks.

PI_NAMEs: WIKENHEISER, ANDREW M (contact)

PROGRAM_OFFICER_NAME: RANGEL GOMEZ, MAURICIO

PROJECT_TITLE: Understanding spatial representations in rat orbitofrontal cortex

STUDY_SECTION: LMDN

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


ADMINISTERING_IC: HD

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

ORG_CITY: STANFORD

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE The goal of the proposed research is to take the first step in developing a safe, accurate, and biopsy-free method for rapid aneuploidy detection in the preimplantation embryo without affecting its viability and developmental potential. The novel technology we will develop here could be used as both a diagnostic and research tool, and would lead to a significant advancement for genetic disease prevention and better understanding of embryo development.

PI_NAMEs: YU, BO  (contact)

PROGRAM_OFFICER_NAME: RAVINDRANATH, NEELAKANTA

PROJECT_TERMS: Acceleration;Adult;advanced maternal age;Affect;Aneuploidy;assisted reproduction;Assisted Reproductive Technology;Biological;Biological Process;Biomedical Engineering;Biopsy;Birth;Birth Rate;blastocyst;Cardiovascular system;cell free DNA;cell type;Cells;chromosome number abnormality;Chromosome Pairing;Chromosomes;Clinical;clinical diagnostics;Color;combinatorial;Couples;Culture Media;Data;Detection;Development;Diagnosis;Diagnostic;diagnostic accuracy;diagnostic tool;disorder prevention;DNA sequencing;Dyes;early pregnancy loss;Embryo;embryo cell;embryo culture;Embryo Loss;Embryo Transfer;Embryonic Development;Engineering;epigenomics;fetal diagnosis;fluorophore;Freezing;Future;Genetic Diseases;Genome;genomic locus;Genomics;Goals;Grant;Growth and Development function;Guide RNA;Half-Life;Health;Human;Image;imaging modality;improved;in utero;In Vitro;in vivo;Individual;Infertility;insight;Karyotype determination procedure;Kinetics;Label;Live Birth;Metabolic;Methods;molecular imaging;Mus;new technology;Newborn Infant;novel;offspring;Oocytes;Outcome;Pregnancy;Pregnancy Outcome;Pregnancy Rate;Preimplantation Diagnosis;Procedures;Process;Proteins;Quantitative Reverse Transcriptase PCR;rapid technique;Reproduction;Reproductive Health;Research;Ribonucleoproteins;Safety;safety testing;screening;Screening Result;Series;single molecule;Somatic Cell;sperm cell;success;Technology;telomere;Testing;Time;time use;Tissues;tool;transcriptome;transcriptome sequencing;transcriptomics;Western Blotting;Woman;zygote

PROJECT_TITLE: Live embryo imaging for biopsy-free aneuploidy detection

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative PUBLIC HEALTH RELEVANCE: Ventral tegmental area (VTA) dopamine neurons are essential for associative learning of reward and aversion-related cues, updating learned associations by prediction errors, as well as supporting a value of rewarding and aversive outcomes that each play foundational roles in psychiatric disorders. While it is well established that VTA dopamine neurons show heterogenous signaling patterns related to these motivationally- relevant events, as well as express diverse molecular characteristics such as the release of dopamine alone or co-release with glutamate, our understanding of how dopaminergic molecular heterogeneity contributes to VTA dopamine neuron functions are unclear. This research program will comprehensively determine the involvement of specific subtypes of dopamine and glutamate VTA neurons, as well as the neurotransmitters they distinctly release, in reward and aversion-based motivated behaviors.

PI_NAMEs: ROOT, DAVID H (contact)

PROGRAM_OFFICER_NAME: HUPALO, SOFIYA

PROJECT_TERMS: addiction;Affect;Association Learning;aversive conditioning;Aversive Stimulus;Behavior;behavior influence;Behavioral;cell type;Characteristics;conditioned place preference;Cues;Data;Discrimination;Disease;Dopamine;dopamine system;dopaminergic neuron;Event;experimental study;gamma-Aminobutyric Acid;Glutamates;Heterogeneity;Impairment;knock-down;learned behavior;Learning;learning extinction;Mental Depression;Mental disorders;Midbrain structure;Molecular;motivated behavior;Motivation;Mus;Negative Reinforcements;Neurons;neurotransmission;neurotransmitter release;Neurotransmitters;Outcome;outcome prediction;Pattern;Phenotype;Play;Positive Reinforcements;programs;public health relevance;Research;Rewards;RNA Interference;Rodent;Role;Self Stimulation;Signal Transduction;Stimulus;System;Testing;Time;Transgenic Organisms;Tyrosine 3-Monooxygenase;Update;vector;Ventral Tegmental Area;vesicular glutamate transporter 2;Virus

PROJECT_TITLE: Untangling dopamine and glutamate neuron function in the VTA

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Contraception/Reproduction;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pregnancy;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: PROVIDENCE

ORG_NAME: WOMEN AND INFANTS HOSPITAL-RHODE ISLAND

ORG_STATE: RI

PHR: PROJECT NARRATIVE National guidelines to reduce maternal mortality from uncontrolled hypertensive disorders of pregnancy (HDP) recommend blood pressure (BP) measurement 3-10 days after discharge and at least one preventive care visit within one year of delivery, yet adverse social determinants of health reduce adherence to these guidelines. The proposed public health study responds to research gaps and needs to address uncontrolled HDP, as recently identified by the US Preventative Services Task Force, by yielding high-quality evidence on the effectiveness of an innovative technology-based, statewide collaborative care model for postpartum people with hypertension—RI-SPHERES—in reducing rates of persistently elevated hypertension in the first six weeks after delivery and increasing the proportion of patients with HDP who receive HTN-related preventive care within a year of childbirth. As part of this study, we also plan to develop an implementation toolkit for widespread dissemination of RI-SPHERES in other states, which would provide a scalable, low-cost intervention that is broadly applicable to communities throughout the country and would reduce the overall incidence of maternal mortality and decrease racial and ethnic disparities for Black/Latinx patients with HDP during the immediate and remote postpartum period.

PI_NAMEs: LEWKOWITZ, ADAM KORRICK (contact)

PROGRAM_OFFICER_NAME: MITCHELL, MEGAN S

PROJECT_TERMS: Address;Adherence;Administrator;Area;Automation;Birth;Black race;Blood Pressure;Blood Pressure Monitors;Bluetooth;Case Manager;Child Care;Childbirth;Chronic;Clinical;collaborative care;Communication;Communities;Consent;Country;Data;Disadvantaged;Disparity;disparity elimination;disparity reduction;Education;Effectiveness;effectiveness evaluation;effectiveness/implementation trial;Enabling Factors;Ensure;ethnic disparity;ethnic minority;Etiology;evidence base;Factor Analysis;geographic disparity;Guidelines;Health;health inequalities;Health Personnel;Health Services;high risk;Home;Hospitals;Hybrids;Hypertension;implementation strategy;improved;Incidence;Infant;innovative technologies;Intervention;intervention cost;Latinx;Long-Term Effects;maternal morbidity;Maternal Mortality;Measurement;Measures;Meta-Analysis;minority patient;Modeling;Morbidity - disease rate;mortality disparity;Multicenter Trials;novel;Outcome;Participant;Patients;Persons;Pilot Projects;Population;Postpartum Hypertension;Postpartum Period;pregnancy disorder;Preventive;Preventive care;primary care visit;programs;Public Health;Race;racial disparity;racial minority;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Reduce health disparities;Research;Rhode Island;Risk;satisfaction;service intervention;severe maternal morbidity;smartphone application;social health determinants;Source;standard care;Symptoms;tailored messaging;Technology;Transportation;United States Preventative Services Task Force;Visit;Woman

PROJECT_TITLE: Effect of a technology-based collaborative care model on persistent hypertension and preventive careattendance among postpartum people with hypertensive disorders of pregnancy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 HSS-B (90)]


NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Congenital Heart Disease;Heart Disease;Orphan Drug;Pediatric;Precision Medicine;Prevention;Rare Diseases

PHR: Project Narrative Sudden cardiac death due to ventricular arrhythmias is the leading cause of death in the U.S., prematurely taking the lives of more than 300,000 U.S. citizens each year. The goal of this project is to use mathematical modeling and computer simulations to discover novel antiarrhythmic therapies to prevent this deadly manifestation of heart diseases and to identify ECG markers for risk prediction.

PI_NAMEs: QU, ZHILIN  (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Accounting;Acute;Aging;Anti-Arrhythmia Agents;Arrhythmia;Arrhythmogenic Right Ventricular Dysplasia;base;Biological;Brugada syndrome;Calcium;Cardiovascular Diseases;Catecholaminergic Polymorphic Ventricular Tachycardia;Cause of Death;Cessation of life;Chronic;circadian;Circadian Rhythms;Clinical;Clinical Data;Clinical Markers;Clinical Medicine;Clinical Trials;Complex;computational platform;Computer Models;Computer Simulation;Consumption;cost;Coupling;Data;Dependence;Deterioration;drug discovery;Drug Targeting;drug testing;effective therapy;Effectiveness;Electrocardiogram;environmental stressor;Evolution;Exhibits;experimental study;Failure;Fibrosis;Functional disorder;Future;Goals;Gonadal Steroid Hormones;Heart Diseases;Heart failure;heart rate variability;human disease;human model;Implantable Defibrillators;in silico;Individual;insight;inter-individual variation;Intervention;Ischemia;ischemic cardiomyopathy;Link;Literature;Long QT Syndrome;mathematical model;Mathematical Model Simulation;Metabolic stress;Molecular;molecular scale;mortality;mortality risk;Mutation;Myocardial Ischemia;Nerve;neural;novel;Pharmaceutical Preparations;Pharmacotherapy;Population;population based;Prediction of Response to Therapy;premature;prevent;Prevention;Property;Regional Disease;repository;Risk;Risk Marker;risk prediction;risk stratification;Seasons;Sex Differences;Short QT syndrome;simulation;Site;Sodium;Stress;Study models;sudden cardiac death;Syndrome;Testing;theories;Therapeutic;therapeutic target;Time;Tissues;Translating;Variant;Ventricular Arrhythmia;Ventricular Fibrillation;Ventricular Tachycardia;virtual clinical trial

PROJECT_TITLE: A population-based computational approach for arrhythmia prediction and therapy

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


NIH_SPENDING_CATS: Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Colorectal cancer accounts for 8-9% of all cancer-related deaths in the U.S. in both women and men, and estimates predict it will account for 52,550 deaths in 2023. The long-term goal for this research is to provide novel therapeutic strategies to treat patients with metastatic disease by targeting PGC-1β signaling. Additionally, we hope to develop treatment strategies with tolerable side effects to lengthen and improve the quality of life after a diagnosis of metastatic colorectal cancer.

PI_NAMEs: FISHER, KURT  (contact)

PROGRAM_OFFICER_NAME: LIU, ZHIHUI

PROJECT_TERMS: Anchorage-Independent Growth;apoptosis inducing factor;Binding;Binding Proteins;cancer survival;cancer therapy;Cell Nucleus;Cell Survival;Cells;Cessation of life;chemotherapy;Cleavage Under Targets and Release Using Nuclease;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;cofactor;Colon;colon cancer cell line;colon cancer patients;Colorectal Cancer;colorectal cancer treatment;CRISPR/Cas technology;Data;Development;Diagnosis;Disease;Drug Targeting;Epigenetic Process;Epithelium;ERR1 protein;Gene Expression;Gene Expression Regulation;Gene Modified;Genes;Genetic Transcription;genome-wide;genomic locus;Glutamine;Goals;Growth;Histone-Lysine N-Methyltransferase;Homeostasis;Human;Immune;Immunodeficient Mouse;Immunoprecipitation;improved;in vivo;in vivo evaluation;inhibitor;Injections;Intestines;Knock-out;KRAS2 gene;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Mediator;men;Metabolic;Metabolism;metastatic colorectal;Metastatic Neoplasm to the Liver;Modeling;mouse model;Multiprotein Complexes;mutant;Mutation;Neoplasm Metastasis;neoplastic cell;novel therapeutic intervention;novel therapeutics;Organoids;overexpression;Patients;Phosphoglycerate Mutase;Phosphoric Monoester Hydrolases;PPAR gamma;prevent;Primary Neoplasm;Prognosis;Protein Dephosphorylation;Protein Family;protein protein interaction;Proteins;Publishing;Quality of life;receptor;Regulation;Research;side effect;Signal Transduction;small molecule;small molecule inhibitor;Submucosa;Survival Rate;targeted cancer therapy;Testing;Therapeutic;therapeutic target;Transcription Coactivator;transcription factor;Transcription Initiation;Transcriptional Regulation;transcriptome sequencing;translational impact;treatment strategy;tumor;tumor growth;Tumor Promotion;tumor xenograft;Woman

PROJECT_TITLE: Assessment of strategies for targeting transcriptional co-activators in colorectal cancer

STUDY_SECTION: GRIC

STUDY_SECTION_NAME: Gene Regulation in Cancer Study Section[GRIC]


ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE The success of chimeric antigen receptor (CAR) T-cell immunotherapy in patients with heterogenous antigen- expressing solid tumors requires effective cytotoxicity and functional persistence of infiltrating CAR T cells in an immunosuppressive environment. Herein, we propose to translate KITv CAR T cells by exploiting multiple IFNγ-mediated cytotoxic mechanisms and adding a PD1 dominant negative receptor to counteract tumor and macrophage mediated immunosuppression.

PI_NAMEs: ADUSUMILLI, PRASAD S. (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Address;anti-PD-1;Antigen Targeting;Antigens;Apoptosis;Avidity;Binding;Biological;Bronchopulmonary Sequestration;C-KIT Mutation;cancer cell;CAR T cell therapy;CD28 gene;CD8B1 gene;Cell Therapy;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;Clinical Trials;cytotoxic;cytotoxicity;Dominant Negative Receptor;Dose;Environment;exhaustion;Helper-Inducer T-Lymphocyte;Hematologic Neoplasms;ICAM1 gene;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immunosuppression;Immunotherapy;in vivo;Infiltration;Infusion procedures;innovation;Interferon Type II;Investigation;kinase inhibitor;Macrophage;Malignant Neoplasms;malignant pleura tumor;Malignant Pleural Mesothelioma;Mediating;mesothelin;Methods;Modeling;Mutation;neoplastic cell;overexpression;Pathway interactions;Patients;pembrolizumab;peripheral blood;phase I trial;Phase I/II Trial;programmed cell death ligand 1;programmed cell death protein 1;Proliferating;Reagent;receptor;Reporting;Research Personnel;Safety;Signal Transduction;Solid Neoplasm;Stress;success;Survivors;Synapses;T-Cell Proliferation;T-Lymphocyte;Toxic effect;Transforming Growth Factor beta;Translating;Translations;tumor;tumor microenvironment;Tumor Promotion;Up-Regulation

PROJECT_TITLE: Tuning KITv CAR T cells for the solid tumor environment

STUDY_SECTION: CIC

STUDY_SECTION_NAME: Cellular Immunotherapy of Cancer Study Section[CIC]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Prevention;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: DALLAS

ORG_DEPT: NEUROLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE The proposed research will develop a real-world data platform to advance clinical research in post-stroke cogni- tive impairment and dementia (PSCID). It is relevant to public health, as it will not only address critical gaps in epidemiology of PSCID, but will also provide a robust scientific foundation to investigate potential therapeutic targets for PSCID that now afflicts 2.2 million stroke survivors in the US. Thus, the proposed research is highly aligned with the goal of the National Plan to Address Alzheimer’s Disease, which seeks to treat and prevent Alzheimer’s disease and related dementias by 2025.

PI_NAMEs: XIAN, YING  (contact)

PROGRAM_OFFICER_NAME: GHALEH, MARYAM X

PROJECT_TERMS: Accounting;acute stroke;Address;Adoption;Aging;Algorithms;Alzheimer's Disease;Alzheimer's disease related dementia;American;American Heart Association;Anti-Hypertensive Agents;Anticoagulants;Area;Blood Platelets;burden of illness;Cardiovascular Diseases;Caregivers;Caring;Clinical;clinical practice;Clinical Research;Clinical Trials;cohort;comorbidity;Complex;Coupled;Cox Proportional Hazards Models;Data;data centers;data platform;data quality;data resource;Data Sources;Databases;Dementia;dementia risk;demographics;design;Development;efficacy evaluation;Epidemiology;ethnic minority;Etiology;Event;experience;Face;Fibrinolytic Agents;Fostering;Foundations;Future;Goals;Guidelines;Healthcare;Heterogeneity;High Prevalence;high risk;Hospitals;Impaired cognition;Incidence;indexing;individualized prevention;innovation;insurance claims;interest;Intervention;Investigation;Ischemia;Ischemic Stroke;Knowledge;Lesion;Light;Link;Location;Medical;Medicare;Medication Management;Microvascular Dysfunction;Minor;Mission;Outcome;patient oriented;Patients;Pharmaceutical Preparations;pharmacologic;Phase;Phenotype;Play;Policies;Population;Population Research;Populations at Risk;post stroke;post stroke cognitive impairment;post stroke dementia;Prevalence;prevent;Prevention;Prevention strategy;Professional Organizations;protective factors;Public Health;racial minority;Recommendation;Records;Recurrence;recurrence prevention;Registries;Research;Research Methodology;Resources;Risk;Risk Estimate;Risk Factors;risk mitigation;Risk Reduction;Role;Sampling;secondary analysis;Secondary Prevention;Severities;Societies;Specific qualifier value;Stains;Stroke;stroke event;stroke patient;Stroke prevention;stroke survivor;Subgroup;theories;Therapeutic;therapeutic target;Underrepresented Populations;United States Centers for Medicare and Medicaid Services;Variant;vascular cognitive impairment and dementia;vascular risk factor;virtual;Woman

PROJECT_TITLE: Post-stroke Cognitive Impairment and Dementia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 HSS-D (90)]


ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: Project Narrative This project will develop a new strategy to engineer “helper” CD4+ T cells that orchestrate the function of other immune cells in tumors to allow these cells to better activate immune responses. We will then apply this strategy to tumor targeting CD4 T cells obtained from patient tumors with the goal of inducing anti-tumor immune responses and clinical benefit in patients. We hope this project will lead to a clinical trial of this approach in patients with melanoma and other solid tumors who have failed existing therapies.

PI_NAMEs: VEATCH, JOSHUA R (contact)

PROGRAM_OFFICER_NAME: CHRISTEN, JAYNE

PROJECT_TERMS: Adoptive Transfer;anti-tumor immune response;Antigen Presentation;Antigen Targeting;Antigen-Presenting Cells;B-Lymphocytes;cancer cell;Cancer Model;Cancer Patient;cancer therapy;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Death;cell killing;Cell Separation;Cells;Cellular Immunity;Clinical;Clinical Trials;cohort;Correlative Study;Data;Development;Disease;Down-Regulation;efficacy evaluation;engineered T cells;Engineering;Flow Cytometry;genetic signature;Goals;Human;humanized mouse;IL18 gene;Immune;immune activation;immune activator;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immune signaling;Immunity;Immunohistochemistry;Immunotherapy;improved;Inflammation Mediators;Inflammatory;Interleukin-12;lymphocyte product;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Melanoma;Melanoma patient;Methods;Modeling;monocyte;mouse model;Mus;Myeloid Cell Activation;Myeloid Cells;neoplastic cell;neutrophil;novel;Operative Surgical Procedures;Outcome;Patients;Population;Process;Production;Prognosis;Property;Regulatory T-Lymphocyte;Research;Resistance;response;Signal Transduction;Signaling Molecule;single cell sequencing;single-cell RNA sequencing;Site;Solid Neoplasm;stem;T cell therapy;T-Lymphocyte;Testing;Therapeutic;therapy resistant;tool;Toxic effect;translational approach;tumor;Tumor Antigens;Tumor Escape;Tumor Expansion;tumor microenvironment;Tumor-Derived;tumor-immune system interactions;Tumor-infiltrating immune cells;Tumor-Infiltrating Lymphocytes;Work

PROJECT_TITLE: Targeting the tumor microenvironment with engineered CD4+ T cells


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Genetics;Immunotherapy;Prevention;Women's Health Research

PHR: Project Narrative Breast cancer is the most common cancer in women worldwide and among the leading causes of death in women, and the vast majority of breast cancer deaths result from metastatic recurrences following treatment. Understanding how cancer cells spread to distant sites, persist as dormant disseminated tumor cells, and eventually recur is essential to developing therapies to kill dormant DTCs and prevent metastatic recurrences. We previously identified a role for the antioxidant transcription factor NRF2 in promoting breast cancer recurrence following therapy, and in this proposal we will build on this work to elucidate the regulation and function of NRF2 in breast cancer metastasis.

PI_NAMEs: ALVAREZ, JAMES V (contact)

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: Affect;Antioxidants;Autopsy;biological adaptation to stress;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Model;breast cancer progression;cancer cell;cancer recurrence;Carcinoma;Cause of Death;Cells;Cessation of life;chemotherapy;cohort;CRISPR screen;Cytotoxic Chemotherapy;Data;Disease;Distant;experimental study;Gene Expression;Gene Expression Profiling;Genetic Epistasis;Genetic Transcription;Goals;Growth;Homeostasis;Human;Immune;immune cell infiltrate;improved;in vivo;Infiltration;Inflammatory;Isogenic transplantation;knock-down;Knock-out;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Mediating;Metabolic;Metabolic Pathway;Metabolic stress;Metabolism;Metastatic breast cancer;Metastatic/Recurrent;molecular targeted therapies;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;novel therapeutics;nucleotide metabolism;Nutrient availability;Oxidation-Reduction;Oxidative Stress;Pathway interactions;Patients;prevent;Process;programs;Publishing;Pyrimidine;Recurrence;Recurrent tumor;Regulation;Relapse;Research;Resistance;Risk;Role;Signal Transduction;Site;targeted treatment;Testing;Therapeutic;therapy development;therapy resistant;transcription factor;transplant model;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;tumor-immune system interactions;Woman;Women's mortality;Work

PROJECT_TITLE: NRF2 suppression of inflammatory signaling and its role in tumor progression

STUDY_SECTION: THI

STUDY_SECTION_NAME: Tumor Host Interactions Study Section[THI]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Dementia;Disability Research;Neurodegenerative;Neurosciences;Rehabilitation;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: PHOENIX

ORG_NAME: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER

ORG_STATE: AZ

PHR: PROJECT NARRATIVE: Stroke remains a leading cause of death and disability worldwide, creating a huge socio-economic societal burden. Aberrant endothelial C3a/C3aR signaling post-stroke exacerbates BBB dysfunction, inflammation, synaptic loss, and functional deficits. Our study will contribute to our understanding of the molecular mechanisms underlying stroke to facilitate the future translation of therapeutics to prevent brain tissue injury and long-term functional and cognitive impairment post-stroke.

PI_NAMEs: AHMAD, SAIF ;DUCRUET, ANDREW FREDERICK (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Acute;acute stroke;Adult;Age;Alteplase;Alzheimer's Disease;Anaphylatoxins;antagonist;Attenuated;Binding;Biochemistry;Blood;Blood specimen;blood-brain barrier disruption;Brain;brain cell;Brain Injuries;Brain Ischemia;brain tissue;C3AR1 gene;Cause of Death;Cells;Cerebral Ischemia;Cerebrovascular Circulation;Cerebrum;cognitive function;Complement;Complement 3a;Complement Activation;complement C3 precursor;complement C3a receptor;Data;density;Development;disability;Edema;Electrophysiology (science);Endothelium;FDA approved;Foundations;functional disability;Functional disorder;Functional impairment;functional outcomes;Future;Generations;Genetic;Goals;Hemorrhage;Histology;Human;Immune;improved;improved outcome;Infarction;Infiltration;Inflammation;Inflammatory;Injury;Intravenous;Ischemia;Ischemic Brain Injury;Ischemic Stroke;Link;Longitudinal Studies;LoxP-flanked allele;Mechanics;Mediating;Microglia;Middle Cerebral Artery Occlusion;Modeling;Molecular;Mus;Myelogenous;Myeloid Cells;Nervous System Physiology;Neurodegenerative Disorders;Neuroglia;Neurologic Dysfunctions;Neurons;neuroprotection;neurovascular injury;novel;old mice;Operative Surgical Procedures;Outcome;Pathogenesis;Pathway interactions;Peripheral;Phagocytosis;Physiological;Plasma;Plasmin;Play;post stroke;post stroke cognitive impairment;postsynaptic;presynaptic;prevent;Process;process improvement;Proteins;receptor;Reperfusion Therapy;repository;Risk;Role;sham surgery;Signal Transduction;socioeconomics;Stroke;stroke model;stroke patient;stroke recovery;Sum;Synapses;synaptic function;synaptic pruning;targeted treatment;Thrombectomy;Time;time interval;tissue injury;Tissues;Translating;translational therapeutics

PROJECT_TITLE: Endothelial complement C3a receptor mediated cerebral injury in a murine stroke model.

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: Project Narrative Antibiotics frequently fail to resolve chronic infections because bacteria in the host environment adopt physiological states that are highly tolerant to antibiotics. Our work investigates how the host nutrient environment drives the bacterial physiologies that underpin chronic infections: slow growth and biofilm formation. Studying clinically-relevant physiologies in diverse bacteria will inspire new therapeutic approaches that are capable of resolving chronic infections.

PI_NAMEs: SPERO, MELANIE A. (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Address;Adopted;Anaerobic Bacteria;Antibiotic Resistance;Antibiotic Therapy;antibiotic tolerance;Antibiotics;Bacteria;bacterial metabolism;Bacterial Physiology;Chronic;chronic infection;clinically relevant;Cues;effective therapy;Environment;Evolution;Genetic;genetic manipulation;Growth;human microbiota;Immune;Infection;Life Style;member;Metabolism;Microbial Biofilms;novel therapeutic intervention;Nutrient;Nutrient availability;Physiological;Physiology;programs;Quantitative Microscopy;Regulation;Research;Techniques;tool;Treatment Failure;Work;wound

PROJECT_TITLE: Nutrient-driven bacterial physiology in recalcitrant infections.

STUDY_SECTION: MRAF

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - F Study Section[MRAF]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Digestive Diseases;Immunotherapy;Pancreatic Cancer;Rare Diseases

PHR: PROJECT NARRATIVE Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis. The unmet need is our inability to provide molecular and metabolic information to characterize of the chronic inflammatory state of the pancreatic tumor microenvironment for delineating the extent of the pancreatic cancer for specific diagnosis and individualized treatments and to monitor treatment responses. The goal of this proposal is to develop a small molecule 18F-CCR2 antagonist as the positron emission tomography (PET) tracer for non-invasive molecular and metabolic imaging of PDAC.

PI_NAMEs: GOODMAN, MARK MYRON (contact);LESINSKI, GREGORY B.

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Address;Affinity;antagonist;anti-tumor immune response;Attention;Autoradiography;Binding;Biopsy;Bone Marrow;Cancer Etiology;CCL2 gene;CD8-Positive T-Lymphocytes;Cell Line;Cells;Cessation of life;chemokine receptor;chemotherapy;Chronic;Classification;Clinical;clinical application;clinical imaging;clinical investigation;clinically relevant;Cyclopentane;Cytotoxic Chemotherapy;Desmoplastic;Detection;Development;Diagnosis;Diagnostic Imaging;Disease;Dose;Drug Delivery Systems;Early Diagnosis;Effectiveness;Epigenetic Process;Excision;Exhibits;Extracellular Matrix;Flow Cytometry;Fluorides;fluorodeoxyglucose;fluorodeoxyglucose positron emission tomography;Functional Imaging;Genetic;Goals;Heterogeneity;Histopathology;Human;Image;imaging agent;imaging capabilities;Imaging Device;imaging modality;imaging probe;Imaging Techniques;Immune;immune cell infiltrate;Immunotherapy;improved;In Vitro;Individual;individualized medicine;Inflammation;Inflammatory;innovation;insight;Investigational Therapies;Leukocytes;Ligands;Macrophage;Magnetic Resonance Imaging;Malignant neoplasm of pancreas;Malignant Neoplasms;Maps;Metabolic;metabolic imaging;Metabolism;microPET;migration;Modality;Molecular;molecular imaging;Molecular Target;Monitor;monocyte;Mus;Myeloid-derived suppressor cells;Nature;neoplasm immunotherapy;non-invasive imaging;Normal tissue morphology;novel;Operative Surgical Procedures;pancreatic cancer model;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic neoplasm;Pancreatitis;Pathway interactions;Patients;Population;Positron-Emission Tomography;Prognosis;Property;Radiolabeled;radioligand;receptor;residence;Resistance;Rodent;Role;Secure;small molecule;Specificity;Survival Rate;T cell infiltration;targeted imaging;Testing;testing uptake;therapy resistant;Time;Tracer;treatment response;tumor;tumor heterogeneity;tumor microenvironment;tumor progression;Tumor Volume;tumorigenesis;uptake

PROJECT_TITLE: Development of a PET CCR2 Imaging Agent to Profile PDAC Microenvironment

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-X (M2)]


NIH_SPENDING_CATS: Genetics;Human Genome;Neurosciences

ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

ORG_STATE: CA

PHR: PROJECT NARRATIVE Developmental motor skills, such as learning to walk or speak, first start as highly variable behaviors that then gradually become more consistent as the skill is successfully learned. Deficits in the stabilization of motor control are associated with motor disorders such as developmental dyspraxia, yet the biological basis of this dysfunction is poorly understood. The goal of the proposed research is to understand the molecular mechanisms in a cortical motor circuit that regulate this transition from variable to precise motor skill action.

PI_NAMEs: COLQUITT, BRADLEY MARK (contact)

PROGRAM_OFFICER_NAME: LEE, CRYSTAL ANNE

PROJECT_TERMS: Age;Animal Model;Apraxia;ATAC-seq;Behavior;Biological;Biological Assay;Biological Models;bird song;Birds;candidate identification;Cell Nucleus;cell type;Cells;Characteristics;Chromatin;Code;Computers;corticotropin releasing factor-binding protein;Corticotropin-Releasing Hormone;critical period;Data;deafening;Dedications;Development;early childhood;Epigenetic Process;Equilibrium;experimental study;Finches;Functional disorder;Gene Expression;Genes;Genetic;Genetic Transcription;genome-wide;Genomics;Goals;Hand;histone modification;homeodomain;hormonal signals;Human;Learning;Learning Skill;Life;Mammals;Mediating;Molecular;Molecular Analysis;molecular modeling;Motor;motor control;Motor Cortex;motor disorder;Motor Pathways;motor skill learning;Motor Skills;Nature;neural;neural circuit;neuromechanism;Neuronal Differentiation;Neurons;Neuropeptides;neurophysiology;neuroregulation;Output;Pathway interactions;Performance;pharmacologic;Physiological;Population;Property;Proteins;Regulatory Element;Research;response;Role;single nucleus RNA-sequencing;skill acquisition;skills;Songbirds;Speech;Synapses;Synaptic plasticity;System;Testing;Time;transcription factor;transcriptomics;tutoring;Walking;Work

PROJECT_TITLE: Molecular mechanisms of motor skill stabilization

STUDY_SECTION: SMN

STUDY_SECTION_NAME: Sensory-Motor Neuroscience Study Section[SMN]


PHR: NARRATIVE In up to 5% of people with diabetes it is due to a defect in a single gene and these varieties of diabetes provide opportunities for precision medicine. A current challenge is our inability to correctly interpret the hundreds of rare and often unique DNA changes in the protein coding sequence of these genes which leads to uncertainty over the genetic diagnosis. We will address this by generating comprehensive variant maps which catalogue the impact of sequence change on protein function and provide a roadmap for implementing similar efforts across all medically actionable diabetes genes to accelerate precision medicine for people with diabetes.

PI_NAMEs: GLOYN, ANNA LOUISE (contact)

PROGRAM_OFFICER_NAME: ZAGHLOUL, NORANN

PROJECT_TERMS: Acceleration;Affect;Affinity;Alleles;Benign;Beta Cell;biobank;Biochemical;Biological Assay;Biomedical Engineering;Catalogs;causal variant;Cell model;cell type;Cells;Chemistry;Classification;Clinical;clinical diagnostics;Code;Complex;Coupled;Coupling;deep learning;Defect;design;Diabetes Mellitus;diabetes risk;Diagnosis;Disease;Dissociation;DNA;DNA Binding;DNA Sequence;Elements;Enzyme Kinetics;Enzymes;Epidemic;exome sequencing;experience;Family member;Fluorescence-Activated Cell Sorting;Functional disorder;Future;Generations;Genes;genetic disorder diagnosis;genetic testing;genome sequencing;global health;Glucokinase;Glucose;Guidelines;hepatic nuclear factor 1;high throughput screening;Human;improved;in silico;In Vitro;Individual;inhibitor;innovation;insight;insulin secretion;interest;International;Maps;Measurement;Medical;Medical Genetics;Methodology;Microfluidics;multiplex assay;Mutation;mutation screening;Nucleotides;Outcome;Pathogenicity;Patients;personalized diagnostics;Persons;pharmacologic;Population;precision medicine;predictive modeling;Prognosis;programs;Protein Array;protein function;protein structure;Proteins;Registries;Reporter;Research;Risk;transcription factor;Uncertainty;Validation;Variant;variant of unknown significance;Work

PROJECT_TITLE: Deep Mutational Scanning of Monogenic Diabetes Genes to Facilitate Precision Diagnostics for Diabetes

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Hepatitis;Hepatitis - B;Immunization;Immunotherapy;Infectious Diseases;Liver Disease;Vaccine Related

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative HBV chronically infects >250 million people and remains a significant public health burden, despite the availability of an effective prophylactic vaccine for more than 30 years. Immunological control of HBV, i.e. functional cure, is possible, as evidenced by HBV natural history in some infected populations, but the immune correlates of protection remain undefined. Here we will define the immune responses mediating functional cure and identify pathways of immune dysfunction that could be targeted by specific immunotherapies.

PI_NAMEs: LAUER, GEORG MICHAEL (contact);LAW, MANSUN ;LEWIS-XIMENEZ, LIA LAURA;ZHANG, YUN

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Acute;Adult;Affect;Animal Model;Antibodies;Antigens;B-Cell Antigen Receptor;B-Lymphocytes;Biological Assay;Biological Models;Brazil;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Physiology;Cells;cellular targeting;Characteristics;Chronic;Chronic Hepatitis B;chronic infection;Clinical;Clinical Research;cohort;Country;Critical Pathways;Data;design;Development;experimental study;Frequencies;Functional disorder;Generations;Genetic Transcription;global health;Goals;Hepatitis;Hepatitis B Prevalence;Hepatitis B Surface Antigens;Hepatitis B Vaccines;Hepatitis B Virus;Hepatitis C virus;High Prevalence;Human;Immune;Immune Evasion;Immune response;Immune System Diseases;Immunity;Immunologics;Immunology;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Impairment;Individual;infection rate;Intervention;Joints;Knowledge;knowledge integration;Measures;Mediating;Mediator;Minority;Molecular;Molecular Profiling;Molecular Target;Natural History;novel;novel therapeutic intervention;Outcome;pathogen;Pathway interactions;patient population;Patients;Pattern;Persons;Phenotype;Population;Preventive vaccine;programs;Property;Public Health;Research;response;Role;seroconversion;Serology;Specimen;Surface;synergism;System;T cell response;T-Lymphocyte;Target Populations;Testing;Tissues;tool;Vaccine Therapy;Vaccines;Viral;Viral Antigens;Viral hepatitis;Viral Pathogenesis;Virus;Virus Diseases;Virus Latency;Virus Receptors;Virus Replication

PROJECT_TITLE: Integrated analysis of HBV-specific CD4 T cell and B cell responses to define their role in chronic hepatitis B and HBV functional cure.


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Biotechnology;Brain Disorders;Epilepsy;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

ORG_DEPT: NEUROSURGERY

PHR: Project Narrative With nearly 68% of all epilepsies now thought to have a genetic cause, including many childhood epilepsies that are in desperate need of more effective therapies, our proposal is squarely focused on a timely and significant unmet need in the epilepsy community. While it is possible to generate mutant mice for all known human epilepsy genes, doing so would be time consuming, expensive and labor intensive. An alternative pre-clinical animal model, zebrafish offer significant advantages for in vivo analysis of gene function and drug discovery.

PI_NAMEs: BARABAN, SCOTT C (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: 3-Dimensional;Address;Animal Model;Anticonvulsants;Artificial Intelligence;Behavior;behavioral phenotyping;Benchmarking;Blinded;Brain imaging;Cardiovascular Diseases;childhood epilepsy;Clinic;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;comorbidity;Complex;Computer software;Consumption;Coupled;Coupling;CRISPR library;CRISPR/Cas technology;design;Diabetes Mellitus;Diagnosis;Disease;DNA Sequence Alteration;dravet syndrome;drug candidate;drug development;drug discovery;drug repurposing;Drug Screening;effective therapy;Epilepsy;Etiology;Exhibits;experience;gene function;Gene Modified;Generations;Genes;Genetic;Genetic Diseases;Goals;high resolution imaging;high risk;high-throughput drug screening;Human;Human Genetics;imaging system;improved;In Vitro;in vivo evaluation;Individual;induced pluripotent stem cell technology;insight;Intractable Epilepsy;Laboratories;lead candidate;Libraries;loss of function;Machine Learning;machine learning algorithm;Malignant Neoplasms;Microscope;Mission;Modeling;multidisciplinary;mutant;Mutant Strains Mice;National Institute of Neurological Disorders and Stroke;Nature;neural network;neurobehavioral;Neurons;novel;novel therapeutics;Optics;patient population;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Population;pre-clinical;pre-clinical therapy;precision medicine;programs;Publishing;Quality of life;Research;Resistance;Resolution;SCN8A gene;screening;Seizures;success;System;Techniques;Testing;Therapeutic;therapy development;Time;tool;Uncertainty;Vertebrates;Work;Zebrafish

PROJECT_TITLE: Deep Behavioral Phenotyping of Novel Zebrafish Epilepsy Models

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]