NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Diagnostics and Prognostics;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Pediatric

ORG_CITY: LITTLE ROCK

ORG_NAME: ARKANSAS CHILDREN'S HOSPITAL RES INST

ORG_STATE: AR

PHR: PROJECT NARRATIVE Respiratory viral coinfections (RVCIs) are more common in children, particularly with the emergence of SARS- CoV-2, but differentiating between coinfection and codetection remains unclear, hindering clinical understanding. We aim to investigate patient features, coinfecting viruses, microbial contributions, and host responses to determine their impact on disease severity in SARS-COV-2-infected children. With a multidisciplinary team and metagenomic next-generation sequencing, we aim to identify immunologic fingerprints specific to SARS-CoV-2, enabling targeted treatment approaches and advancing our knowledge regarding the clinical implications of finding multiple viruses on respiratory pathogen testing.

PI_NAMEs: KENNEDY, JOSHUA  (contact)

PROGRAM_OFFICER_NAME: NATARAJAN, ARUNA R

PROJECT_TERMS: 2019-nCoV;5 year old;Acute respiratory infection;Adult;Affect;Age;Algorithms;Area Under Curve;Arkansas;Characteristics;Child;Clinical;clinical material;Clinical Trials;co-infection;comorbidity;COVID-19 treatment;Data;Disease;Enterovirus;Epidemiology;Ethnic Origin;experience;Fingerprint;Future;Gender;Gene Expression;Genes;Genetic Materials;Immune response;Immune System Diseases;Immunologics;Immunomodulators;improved;improved outcome;Individual;Infection;Institution;interest;Knowledge;Laboratories;Lower Respiratory Tract Infection;Metagenomics;Methods;Microbe;microbial;Modeling;Monoclonal Antibodies;multidisciplinary;nasopharyngeal swab;Nasopharynx;next generation sequencing;novel;Outcome;pathogenic microbe;Pathogenicity;Patients;Pediatric Hospitals;pediatric patients;pediatrician;predictive modeling;Prevention;Prognosis;Race;Recording of previous events;Research Personnel;respiratory;respiratory pathogen;Respiratory syncytial virus;Respiratory Syncytial Virus Infections;Rhinovirus;Risk;Sampling;SARS-CoV-2 infection;SARS-CoV-2 variant;Severe Acute Respiratory Syndrome;severe COVID-19;Severities;Severity of illness;Site;Specimen;Steroids;Symptoms;targeted therapy trials;targeted treatment;Testing;tocilizumab;Vaccination;Ventilator;Viral;viral detection;Virus;Virus Diseases;virus host interaction;virus testing;World Health Organization

PROJECT_TITLE: An Integrated Host-Microbe Gene Classifier to Predict SARS-CoV-2 and Severe Disease in Children with Respiratory Viral Coinfections

STUDY_SECTION: PRID

STUDY_SECTION_NAME: Population based Research in Infectious Disease Study Section[PRID]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Asthma;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Patient Safety;Pediatric;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: Project Narrative Asthma is a leading cause of childhood morbidity and disparities nationwide and limited provider adoption of and patient adherence to the prevailing evidence-based recommendations for chronic management represent tractable areas for implementation focus. In their 2020 Focused Updates to the National Asthma Management Guidelines, the NHLBI recommended single maintenance and reliever therapy (SMART) - a paradigm-shifting approach to chronic asthma management that combines an immediate-acting reliever and longer-acting maintenance inhaler medications that are generally taken separately - as the preferred chronic management strategy for persistent moderate to severe asthma based on robust efficacy and real-world effectiveness in international settings. Several important barriers, however, hinder current SMART adoption in the US; the proposed project will test two theoretically grounded and empirically supported implementation strategies to improve SMART adoption in pediatric primary care, while also assessing real-world effectiveness in a large health system whose racial demographics mirror US asthma morbidity statistics.

PI_NAMEs: KENYON, CHEN COLLIN (contact)

PROGRAM_OFFICER_NAME: FREEMER, MICHELLE M

PROJECT_TERMS: Address;Adherence;Adopted;Adoption;Age;Area;arm;Asthma;asthma exacerbation;asthma inhaler;Authorization documentation;Black race;Care given by nurses;care outcomes;Caregivers;Caring;Case Manager;Child;Childhood;Childhood Asthma;Chronic;Clinic;Clinical;clinical decision support;cluster randomized design;cohort;Community Health Aides;Confusion;Consolidated Framework for Implementation Research;conventional therapy;Country;demographics;design;Disparity;disparity reduction;dissemination strategy;Education;Education and Outreach;Effectiveness;effectiveness trial;effectiveness/implementation study;effectiveness/implementation trial;Electronic Health Record;Eligibility Determination;Emergency department visit;Enrollment;Equity;evidence base;evidence based guidelines;Evidence based practice;experience;Family;Goals;Guidelines;health equity;health management;Health Personnel;Health system;Hospitalization;human centered design;implementation barriers;implementation determinants;implementation outcomes;implementation science;implementation strategy;implementation trial;improved;improved outcome;Informatics;Inhalators;Insurance;International;Intervention;Maintenance;Manuals;Maps;Mediating;medication compliance;Methods;Morbidity - disease rate;National Heart, Lung, and Blood Institute;Negative Reinforcements;Outcome;outcome disparities;Patient Compliance;Patient Education;Patients;Pediatric Hospitals;pediatrician;Penetration;Pharmaceutical Preparations;Phase;Philadelphia;point of care;Population;population health;Prevalence;Primary Care;primary care clinic;primary care practice;primary outcome;programs;Provider;provider adoption;Psychological reinforcement;Race;racial disparity;racial diversity;Racial Equity;Randomized;Recommendation;Research Personnel;Resources;Risk;Safety;Schools;secondary outcome;Self Efficacy;social;statistics;Support System;Symptoms;System;Techniques;Testing;Training;treatment as usual;United States;Update;Use Effectiveness;Visit;Work

PROJECT_TITLE: Single Maintenance And Reliever Therapy Strategies for Implementation and Effectiveness Trial

STUDY_SECTION: SIHH

STUDY_SECTION_NAME: Science of Implementation in Health and Healthcare Study Section[SIHH]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anorexia;Behavioral and Social Science;Brain Disorders;Clinical Research;Eating Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Nutrition;Prevention;Serious Mental Illness;Social Determinants of Health

ORG_CITY: CHAPEL HILL

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE / RELEVANCE The Eating Disorders Genetics Initiative 2 (EDGI2) unites existing and exceptionally productive and collaborative sites globally to advance genetic discovery across all eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder). We will apply both novel and established methods to optimize discovery in our diverse and severely ill sample, culminating in a clinical translation summit. Our goal is to identify biologically, clinically, culturally, and therapeutically meaningful and actionable insights and rapidly transition the field from discovery to clinical translation.

PI_NAMEs: BULIK, CYNTHIA M (contact);COMPTE, EMILIO ;HUCKINS, LAURA MARIANNE;TRUJILLO CHI VACUAN, EVA MARIA

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Adipose tissue;Alleles;Anorexia Nervosa;Atlases;Australia;avoidant restrictive food intake disorder;Behavior;Binge eating disorder;Bioinformatics;Biology;Body mass index;Brain;brain cell;Bulimia;Businesses;cell type;Clinical;Clinical Research;clinical translation;cohort;Collection;Communities;community partners;comorbidity;Data;Denmark;Diagnosis;Diagnostic;Dimensions;Disease;disorder prevention;DNA;Eating Disorders;Enrollment;Environmental Exposure;Environmental Risk Factor;Etiology;evidence base;Gene Expression;Genes;Genetic;genetic analysis;Genetic Diseases;Genetic Risk;genome wide association study;Genomics;Genotype;Genotype-Tissue Expression Project;Goals;Grouping;Heritability;Heterogeneity;Human Resources;Individual;innovation;insight;Intervention;Knowledge;Liver;marginalization;marginalized community;Mendelian randomization;Mental Depression;Mental disorders;Meta-Analysis;Metabolic;Metabolic Diseases;Methods;Mexico;Minority;minority communities;Minority Enrollment;Modeling;Molecular;molecular subtypes;Muscle;Nervous System Disorder;Neurosciences;New Zealand;novel;Participant;Pathway interactions;patient stratification;patient subsets;Pattern;Phase;Phenotype;polygenic risk score;Production;Productivity;psychiatric genomics;Psychiatry;rare variant;recruit;Regional Anatomy;resilience factor;Resources;response;risk prediction;Role;Salivary;Sample Size;Sampling;Science;Severities;sex;single nucleus RNA-sequencing;Site;social media;Stress;Stressful Event;Subcellular Anatomy;Sweden;symposium;Symptoms;Taxonomy;Therapeutic;therapy development;Thinking;Tissues;trait;Underrepresented Populations;Variant;Weight Gain;working group

PROJECT_TITLE: 1/3 Eating Disorders Genetics Initiative 2 (EDGI2)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 EPH-D (65)]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;Lung;Neurosciences;Opioid Misuse and Addiction;Opioids;Sleep Research;Substance Misuse

ORG_CITY: COLLEGE STATION

ORG_DEPT: PHYSIOLOGY

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

ORG_STATE: TX

PHR: The opioid epidemic is one of the most challenging public health crises of our time and sleep apnea patients are among the most vulnerable to suffer fatal opioid overdose. The focus of this proposal is two-fold: (1) identify the failing neurocircuitry that underlies sleep apnea-related hypersensitivity to opioid-induced respiratory depression and (2) address the clinical need for treatments that counter central opioid-induced respiratory depression without interrupting the pain-killing action of opioids and while avoiding central withdrawal effects. This research will advance our understanding of novel targets that can improve the clinical safety of opioids, especially in those most at-risk for their lethal consequences.

PI_NAMEs: TONEY, GLENN M (contact)

PROGRAM_OFFICER_NAME: NAIR, SUNILA GOPI

PROJECT_TERMS: Absence of pain sensation;Acute;Address;Agonist;Analgesics;Animal Model;Anti-Anxiety Agents;Apnea;Arousal;Binding;Biological;Brain;Carotid Body;Cause of Death;Cell Nucleus;Chemoreceptors;Chronic;chronic pain;Clinical;clinically significant;combat;defense response;defined contribution;Depressed mood;depressive symptoms;design;Development;Dose;drug seeking behavior;endogenous opioids;experience;Exposure to;Fentanyl;Genetic;Hormones;Hydrocortisone;Hyperactivity;Hypersensitivity;Hypertension;Hyperventilation;Hypothalamic structure;Hypoxia;Impairment;improved;improvement on sleep;in vivo;indium arsenide;inhibitor;Interruption;Mediating;Membrane Potentials;Modeling;mu opioid receptors;Mus;Naloxone;neural circuit;Neurons;neurotransmission;Neurotransmitters;novel;novel therapeutics;Obstructive Sleep Apnea;Opioid;Opioid Analgesics;opioid epidemic;opioid overdose;Opioid Receptor;opioid therapy;opioid use disorder;opioid withdrawal;optogenetics;overdose death;Oxytocin;Oxytocin Receptor;Pain;paraventricular nucleus;patch clamp;Patients;pharmacologic;Pharmacology;Play;Pontine structure;prevent;Prevention;Public Health;Receptor Activation;Receptor Inhibition;Receptor Signaling;Reporting;Research;Resistance;respiratory;response;restraint;Resuscitation;Risk;Safety;Severities;Signal Transduction;Sleep Apnea Syndromes;Slice;Stress;stress reduction;symptomatic improvement;Symptoms;Testing;Time;Up-Regulation;Ventilatory Depression;Viral;Withdrawal;Withdrawal Symptom

PROJECT_TITLE: Oxytocin Neurotransmission Overcomes Sleep Apnea-Related OIRD Hypersensitivity

STUDY_SECTION: MCNP

STUDY_SECTION_NAME:
Molecular and Cellular Neuropharmacology Study Section
[MCNP]


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: NOTRE DAME

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF NOTRE DAME

ORG_STATE: IN

PHR: Project Narrative Since isoform-selective inhibitors of Grp94 represent a new approach toward the treatment of multiple forms of glaucoma, we propose herein to optimize and elucidate the mechanism by which Grp94 can be used for the potential treatment of glaucoma.

PI_NAMEs: BLAGG, BRIAN S J (contact);LIEBERMAN, RAQUEL L

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Acceleration;Adolescent;Age;age related;Alzheimer's Disease;analog;Anterior;Aqueous Humor;Binding;Biochemical;Biological;Blindness;Cell Culture Techniques;Cell Death;Cell model;Cells;Cellular Stress;Client;Clinic;Collaborations;Complex;Crystallization;cytotoxic;cytotoxicity;Data;Development;Disease;Dose;efficacy evaluation;Endoplasmic Reticulum;endoplasmic reticulum stress;Exhibits;Eye;Functional disorder;gain of function;Glaucoma;Goals;GRP gene;Health;Heat-Shock Response;Human;improved;In Vitro;in vitro Assay;in vivo;inhibitor;insight;Lead;Link;Modeling;Molecular Chaperones;Molecular Target;mouse model;Mus;mutant;Mutate;Mutation;myocilin;nerve damage;Neurodegenerative Disorders;Neurons;novel strategies;Ocular Hypertension;Optic Nerve;Outcome;Parkinson Disease;Patients;Perfusion;Persons;Pharmaceutical Preparations;Phenotype;Physiologic Intraocular Pressure;pre-clinical assessment;prevent;Primary Open Angle Glaucoma;Procedures;Protein Isoforms;protein misfolding;Proteins;proteostasis;Publishing;Retina;Retinal Ganglion Cells;Risk Factors;Rodent Model;Role;screening;small molecule inhibitor;Steroids;Structure;Structure-Activity Relationship;Symptoms;System;Testing;Therapeutic;therapeutic target;Tissues;TLR4 gene;Topical application;Toxic effect;Trabecular meshwork structure;Translating;United States;Validation

PROJECT_TITLE: Selective Inhibition of GRP 94 to Treat Ocular Hypertension and Glaucoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 NV-P (81)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Lung Cancer;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: PROJECT NARRATIVE Black adults with cancer have twice the risk of poor cardiovascular disease (CVD) outcomes compared to White adults with cancer; and we hypothesize that social determinants of health (SDOH) such as structural racism and individual-level socio-economic position are partially responsible for this observed Black-White disparity. The goal of this proposed R01 application is to elucidate the role of SDOH including structural racism on CVD outcomes among a Black and White, community-based cohort of nearly 8,000 male and female adults with cancer. Our proposed work will generate new evidence to inform interventions designed to eliminate Black-White disparities in CVD outcomes during survivorship.

PI_NAMEs: PINHEIRO, LAURA C (contact)

PROGRAM_OFFICER_NAME: WEAVER, SALLIE JAYNE

PROJECT_TERMS: adjudication;Adult;Adult women;Age Years;American;Area;Behavioral;Biological;Biological Factors;Biometry;Black Populations;Black race;black/white disparity;cancer care;cancer diagnosis;cancer epidemiology;cancer health disparity;cancer risk;Cancer Survivor;Cancer Survivorship;cancer therapy;Cardiology;Cardiotoxicity;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;Caring;Categories;Cause of Death;Censuses;Cessation of life;cohort;Communities;comorbidity;Coronary heart disease;Data;Data Sources;Diabetes Mellitus;Diagnosis;disease disparity;Disease Outcome;Disparity;disparity reduction;economic indicator;Education;Event;Female;Financial Hardship;financial toxicity;General Population;geographic disparity;Goals;Health;Health behavior;health care service utilization;health service use;Health Services;Health Services Research;Healthcare;Healthcare Systems;Heart failure;Hospitalization;human old age (65+);Hypertension;Incidence;Income;Individual;Inequity;Intervention;Link;Longitudinal cohort study;Low income;male;Malignant Breast Neoplasm;Malignant Neoplasms;Measures;Medicare;Mental Depression;Mental Health;Modeling;Morbidity - disease rate;mortality;multidisciplinary;neoplasm registry;novel;Obesity;Oncology;Outcome;Participant;Pattern;Play;policy implication;Politics;Population;Prevalence;Primary Care;prospective;psychosocial;Psychosocial Factor;racial disparity;recruit;Registries;residential segregation;Resources;Risk;Risk Factors;Role;Smoking;social health determinants;social structure;Socioeconomic Factors;Socioeconomic Status;socioeconomics;Stress;Stroke;structural determinants;Structural Racism;Survivors;survivorship;System;therapy design;Time;US State;virtual;Work;World Health Organization

PROJECT_TITLE: Structural Racism and Cardiovascular Outcomes Among Cancer Survivors

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 TCRB-9 (J2)]


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);Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: ORANGEBURG

ORG_NAME: NATHAN S. KLINE INSTITUTE FOR PSYCH RES

PHR: PROJECT NARRATIVE: The goal of this collaborative study is to investigate the physiological and pathological roles of mitovesicles, a recently discovered subtype of extracellular vesicles of mitochondrial origin in the brain. We will investigate the mechanisms that modulate mitovesicle production and secretion, their intracellular fate once taken up by recipient cells, and the effects of mitovesicles derived from normal brains and from Alzheimer’s disease- relevant mouse models. Our studies aim to identify novel directions for therapeutic strategies that can restore the integrity of mitochondria, minimizing the effects of this pathology in neurodegenerative diseases such as Alzheimer’s disease.

PI_NAMEs: D'ACUNZO, PASQUALE ;LEVY, EFRAT  (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: abeta deposition;Affect;Age;Age Months;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Amyloidosis;Astrocytes;Autophagocytosis;behavior test;Behavioral;beta amyloid pathology;Bioenergetics;Biogenesis;Biological Markers;Biology;Brain;brain tissue;Cell Survival;Cells;Cellular Metabolic Process;Data;Dementia;Diploidy;Disease;Distal;Down's Syndrome;Equilibrium;Excision;experimental study;Extracellular Space;extracellular vesicles;Female;Functional disorder;Generations;Genetic;Goals;Health;Hippocampus;Homeostasis;Human;Impairment;In Vitro;in vivo;Inflammation;Knock-in;Laboratories;Life Cycle Stages;Link;lipidomics;Long-Term Potentiation;Lysosomes;male;Memory;Microglia;Mitochondria;mouse model;Mus;Names;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;neuronal survival;Neurons;non-demented;Normal tissue morphology;novel;overexpression;Pathogenicity;Pathologic;Pathology;Phase;Physiological;Physiology;Play;postsynaptic;potential biomarker;presynaptic;Production;Proteomics;Quality Control;Reactive Oxygen Species;Regulation;Rest;Role;Sampling;sex;Site;Source;success;Synapses;Synaptic Transmission;tau Proteins;Techniques;Testing;Therapeutic;Time;transcriptome sequencing;uptake;wasting

PROJECT_TITLE: A new perspective on the role of extracellular vesicles in Alzheimer's disease

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


ADMINISTERING_IC: LM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Machine Learning and Artificial Intelligence

ORG_CITY: LEXINGTON

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Large protein language models have shown their foundational role in biomedical research, but the current models miss critical knowledge about protein structure and functions and lack efficient approaches to be adapted for challenging biomedical tasks. To address these two challenges, we propose to develop structure-function-aware large protein language models and adaptation methods for accurate predictions of protein properties. The success of this project will provide novel large protein language models and fundamental deep learning tools for various biomedical applications.

PI_NAMEs: SHAO, QING  (contact)

PROGRAM_OFFICER_NAME: BINGHAM, CLAYTON SCOTT

PROJECT_TERMS: 3-Dimensional;Address;Amino Acid Sequence;anti-microbial peptide;Awareness;bacterial resistance;Base Sequence;Biomedical Research;cancer cell;cancer therapy;Classification;Code;Collaborations;Communities;Data;Data Set;Databases;deep learning;design;Development;Enzymes;Generations;Goals;human disease;in silico;Individual;Knowledge;Language;Learning;learning algorithm;Libraries;loss of function;Methods;model development;Modeling;Molecular;novel;Outcome;overexpression;Performance;Phosphorylation;Phosphotransferases;PLK1 gene;Policies;Procedures;Process;Property;protein function;protein structure;Proteins;Psychological reinforcement;Pythons;Research;Rewards;Role;shot learning;Structure;success;SwissProt;Technology;Therapeutic;three dimensional structure;tool;Training;training data;vector;Work

PROJECT_TITLE: Structure-Function-Aware Large Protein Language Models for Enhanced Biomedical Applications

STUDY_SECTION: BLR

STUDY_SECTION_NAME: Biomedical Informatics, Library and Data Sciences Review Committee[BLR]


ADMINISTERING_IC: DC

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Brain Disorders

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

ORG_STATE: CA

PHR: Narrative The stability of the fluid within your inner ear is crucial for maintaining hearing and balance. Our research will identify how cells communicate to promote development of the ear's pressure control system and how system- wide signals and local forces work to maintain inner ear function. This knowledge will help identify new ways to diagnose and treat hearing and balance disorders.

PI_NAMEs: SWINBURNE, IAN ANDREW (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: Acceleration;Actins;Adhesions;Adhesives;Animals;Argipressin;Atlases;Autophagocytosis;Behavior;Binding;Biological;Calcium;calcium indicator;Calcium Signaling;cell behavior;Cell Communication;Cell-Cell Adhesion;Cells;Complex;congenital deafness;Contractile Proteins;controlled release;deafness;Development;Diagnosis;Disease;Down-Regulation;Ear;ear development;Embryo;Endolymph;Endolymphatic duct;Endolymphatic Hydrops;endolymphatic sac;Environment;Epithelium;equilibration disorder;Equilibrium;Etiology;Eye;fluid flow;Frequencies;Gene Expression;Generations;Genes;Genetic;genome editing;Glaucoma;Goals;hair cell regeneration;Hearing;hearing impairment;Hearing problem;High Prevalence;Homeostasis;hormonal signals;Hormones;Human;Image;Individual;Kidney;Kidney Diseases;Knowledge;Labyrinth;Larva;Ligands;Liquid substance;Lysosomes;mechanical signal;Meniere's Disease;Microscopy;Molecular;Mus;mutant;Mutation;Myosin ATPase;novel therapeutic intervention;Optics;optogenetics;Organ;Pathology;Pathway interactions;Pattern;Pendred Syndrome;Pharmacotherapy;Physiological;Physiology;Piezo 1 ion channel;Plasma;pressure;prevent;Process;programs;protein degradation;Proteins;Pump;receptor;Regulation;Reporter;Research;Resistance;response;Rodent;Role;Rupture;sensor;Signal Pathway;Signal Transduction;Signaling Protein;small molecule inhibitor;sound;spatiotemporal;Stretching;Syndrome;System;TACSTD1 gene;Technology;Temporal bone structure;Testing;Tissues;transcription factor;Vasopressins;Vasotocin;Vestibular Aqueduct;WNT Signaling Pathway;WNT9A gene;Work;Zebrafish

PROJECT_TITLE: Molecular regulation of fluid pressure homeostasis in the inner ear

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biotechnology;Diabetes

ORG_CITY: SALT LAKE CITY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: NARRATIVE While lifesaving, insulin therapy suffers from several shortcomings including the lack of availability of truly monomeric analogs that have a fast onset and offset of action. We recently discovered that venomous cone snails have evolved a diverse set of monomeric insulin analogs, so-called evologs, that provide entirely new opportunities for addressing current challenges in insulin analog design. In this proposal, we will elucidate the full diversity and structure-function of insulin evologs found in nature and utilize this information to design future drug leads for diabetes.

PI_NAMEs: SAFAVI-HEMAMI, HELENA  (contact)

PROGRAM_OFFICER_NAME: SECHI, SALVATORE

PROJECT_TERMS: Address;analog;analytical ultracentrifugation;Animal Model;Animals;Artificial Intelligence;Binding;Biophysics;Blood Glucose;blood glucose regulation;Chemicals;Clinical Drug Development;Collection;Cone;Cryoelectron Microscopy;Data;design;Development;diabetes management;Diabetes Mellitus;diabetes mellitus therapy;dimer;DNA;drug candidate;Drug Kinetics;effective therapy;Ethanol;Evolution;exenatide;Fish Venoms;Fishes;Future;Geography;Gestational Diabetes;glucagon-like peptide 1;Glucose;glycemic control;Hormones;Human;Hybrids;Hypoglycemia;improved;in vivo evaluation;Individual;Injections;Insulin;Insulin Receptor;Insulin-Dependent Diabetes Mellitus;Investigation;Lead;Libraries;Licensing;Life;marine;Metabolic;Modeling;Molecular;monomer;Names;Nature;next generation sequencing;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutics;Pancreas;peptide hormone;Peptide Synthesis;Performance;Persons;Pharmaceutical Preparations;pharmacologic;Phase;pre-clinical;prevent;Production;Property;Protein Isoforms;Publishing;rational design;receptor;Receptor Activation;scaffold;Sequence Analysis;Shapes;Signal Transduction;simulation;Snail Venoms;Snails;Solid;Source;Streptozocin;Structure;subcutaneous;Surveys;System;Techniques;Therapeutic;therapeutic development;Tissue Preservation;Toxin;translational impact;Venoms;Work

PROJECT_TITLE: Discovery and design of novel insulin evologs from venomous marine cone snails

STUDY_SECTION: CSB

STUDY_SECTION_NAME: Chemical Synthesis and Biosynthesis Study Section[CSB]


NIH_SPENDING_CATS: Cancer;Estrogen;Genetics;Uterine Cancer;Women's Health Research

PHR: PROJECT NARRATIVE Estrogen signaling plays a critical role in the development of endometrial cancer; however, it may not be sufficient to drive tumor formation as endometrial cancer usually arises in the context of common mutations and excess estrogens. The goal of the project is to determine how ARID1A mutations, which are common in endometrial tumors, cooperate with estrogen signaling and explore novel treatment strategies for the majority of endometrial cancers, which have ARID1A alterations and active estrogen signaling.

PI_NAMEs: CAIRNS, BRADLEY R.;GERTZ, JASON  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Affect;Agar;Animal Model;ARID1A gene;ATP phosphohydrolase;Binding;Biochemical;cancer cell;cancer type;cell growth;Cells;Cessation of life;Chromatin;Chromatin Loop;Clinical;Collection;Complex;Data;data integration;Development;Disease;DNA-Directed RNA Polymerase;efficacy evaluation;Endometrial;Endometrial Carcinoma;Endometrial Neoplasms;Endometrium;ESR1 gene;Estrogens;Exhibits;Frequencies;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;genome-wide;Genomics;Goals;Growth;Hormonal;Human;Hyperplasia;in vivo;Incidence;inducible gene expression;inhibitor;innovation;Invaded;Knock-out;Literature;loss of function;Malignant Female Reproductive System Neoplasm;Malignant Neoplasms;member;migration;Modeling;Molecular;mortality;mutant;Mutate;Mutation;novel;Nucleosomes;Oncogenes;Oncogenic;Pathway interactions;Pharmacologic Substance;Phenotype;Play;Portraits;Proteins;recruit;Resources;Risk Factors;Role;Signal Pathway;Signal Transduction;Slide;Somatic Mutation;Survival Rate;The Cancer Genome Atlas;three dimensional cell culture;Transcriptional Regulation;treatment strategy;tumor;tumor progression;Tumor Suppressor Proteins;United States;Variant;Work

PROJECT_TITLE: The combined role of ARID1A loss and estrogen signaling in endometrial cancer

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biotechnology;Cancer;Cancer Genomics;Cardiovascular;Childhood Obesity;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Obesity;Pediatric;Pediatric Cancer;Precision Medicine;Prevention;Radiation Oncology;Rare Diseases;Rehabilitation

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: PROJECT NARRATIVE In the current proposal, we plan to employ an integrated genomics-based approach to investigate common cardiometabolic outcomes including five conditions that increase cardiovascular disease risk (abnormal glucose metabolism, obesity, hypertension, hypertriglyceridemia and hypercholesterolemia), and two outcomes of cardiac damage (cardiomyopathy and myocardial infarction) among survivors of childhood and adolescent cancer. Our research framework will address the roles of genetic factors (specifically, rare pathogenic germline variants in multiple relevant pathways), epigenetic factors (specifically, DNA methylation and altered gene expression), as well as multiple biomarkers of aging in cardiometabolic risk within the context of long-term impact from cancer treatment exposures and enduring effects from health behaviors. The successful completion of this project will provide translational pathways towards novel surveillance and intervention strategies for improvement of survivorship care and also generate new hypotheses for future collaborative basic science research.

PI_NAMEs: WANG, ZHAOMING  (contact)

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: Address;Adolescent;Aftercare;Age;age related;Aging;aging biomarker;Anthracycline;Applications Grants;Basic Science;Biological;Biological Aging;Biological Markers;Blood specimen;Cancer Survivor;cancer therapy;Cardiac;cardiometabolic risk;cardiometabolism;Cardiomyopathies;Cardiotoxicity;Cardiovascular Diseases;cardiovascular disorder risk;Caring;Cessation of life;chemotherapy;Chest;chest irradiation;Childhood;childhood cancer survivor;Childhood Cancer Survivor Study;Clinical assessments;cohort;Communities;Complex;Data;Databases;design;Development;DNA Methylation;DNA Repair Gene;drug metabolism;early experience;early onset;Epigenetic age;Epigenetic Process;epigenetic profiling;experience;Exposure to;Functional disorder;functional genomics;Future;Gene Expression;Genetic;Genetic Predisposition to Disease;Genetic Risk;genetic variant;genome sequencing;Genomics;Germ-Line Mutation;glucose metabolism;Health behavior;health disparity;heart damage;Hematopoiesis;high risk population;hypercholesterolemia;Hypertension;Hypertriglyceridemia;Immune response;improved;Individual;Inflammation;Inherited;innovation;inter-individual variation;Intervention;Investigation;Knowledge;Length;Leukocytes;Link;Longitudinal Studies;Malignant Childhood Neoplasm;Malignant Neoplasms;Measures;Mediating;Mediator;Methylation;mortality;multidisciplinary;Multiomic Data;multiple omics;Myocardial Infarction;Nature;novel;Obesity;Organ;Outcome;Pathogenesis;Pathogenicity;Pathway interactions;polygenic risk score;prevent;Publishing;Quantitative Trait Loci;Radiation therapy;Recording of previous events;Research;Research Design;Resources;response;Risk;Risk Factors;Risk Marker;risk stratification;Role;Saint Jude Children's Research Hospital;Site;surveillance strategy;Survivors;survivorship;telomere;Therapeutic;Time;trait;transcriptome sequencing;treatment risk;Treatment-Related Cancer;Variant;whole genome

PROJECT_TITLE: Genomics-based Mechanistic Investigation of Cancer-treatment Related Cardiotoxicity among Survivors of Childhood Cancer

STUDY_SECTION: CHD

STUDY_SECTION_NAME: Cancer and Hematologic Disorders Study Section[CHD]


PHR: PROJECT NARRATIVE Mycophenolic acid (MPA) is a crucial immunosuppressant that prevents acute rejection in kidney transplant recipients but also causes adverse toxicities that threaten its efficacy. Our current understanding of the relationship between gut bacteria and these adverse toxicities is incomplete. Here, we seek to identify the gut microbial enzymes associated with these adverse toxicities and determine whether these microbial enzymes can be used as a predictor of MPA-associated toxicities.

PI_NAMEs: LEE, JOHN RICHARD (contact)

PROGRAM_OFFICER_NAME: ABBOTT, KEVIN C

PROJECT_TERMS: Acute;Animals;Antibiotics;Area Under Curve;Automobile Driving;Beta-glucuronidase;Biological Assay;Biological Markers;Circulation;Clinical;clinical practice;cohort;Data;Development;Diarrhea;dosage;Dose Limiting;Drug Kinetics;enzyme activity;Enzymes;Exhibits;fecal transplantation;Feces;gastrointestinal;Goals;Graft Rejection;gut bacteria;gut microbiota;Immunosuppressive Agents;improved;In Vitro;Kidney Transplantation;Leukopenia;Measurement;Measures;Mediating;microbial;microbiota;microbiota composition;Mycophenolic Acid;novel marker;organ transplant rejection;Organ Transplantation;patient variability;Patients;personalized approach;Pharmaceutical Preparations;Physicians;Play;post-transplant;prevent;Proteomics;recruit;Research;Role;side effect;Specimen;Testing;Therapeutic;Toxic effect;Transplant Recipients;Transplantation

PROJECT_TITLE: Gut microbial beta-glucuronidases as a biomarker for mycophenolic acid enterohepatic recirculation and associated toxicities

STUDY_SECTION: DBDT

STUDY_SECTION_NAME: Drug and Biologic Disposition and Toxicity Study Section[DBDT]


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: Plasminogen is a multi-functional protein that transports lipids and small non-coding RNAs. Plasminogen can transfer small RNAs to macrophages and regulate gene expression and immune cell phenotypes. We aim to gain a fundamental understanding of this novel process, and its relationship to systemic cholesterol metabolism and inflammation, to advance hematology research.

PI_NAMEs: VICKERS, KASEY C (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: Activities of Daily Living;Affinity;base;Binding;Binding Proteins;Biological Process;Blood;Bone Marrow;C-terminal;Cell Communication;cell type;Cells;Cholesterol;Cholesterol Homeostasis;Circulation;Coagulation Process;Complex;Confocal Microscopy;Custom;cytokine;Cytokine Gene;Deposition;Disease;Endoplasmic Reticulum;Endosomes;Enzyme Precursors;Enzymes;extracellular;extracellular vesicles;fascinate;Feedback;Fluorescence;gain of function;Gene Expression;Gene Expression Regulation;Genes;Health;Hematology;High Density Lipoproteins;hypercholesterolemia;Immune;In Vitro;in vivo;Inflammation;Inflammatory;intercellular communication;Label;Ligands;Lipid Binding;lipid transport;Lipids;Lipoprotein (a);Lipoproteins;loss of function;Low-Density Lipoproteins;Lysine;Macrophage;Macrophage Activation;Mass Spectrum Analysis;Mediating;Methyltransferase;microRNA delivery;MicroRNAs;Modification;Molecular Sieve Chromatography;Mus;Myeloid Cells;nanopore;novel;Nuclear;Organelles;particle;Pathway interactions;Pattern recognition receptor;Peptide Hydrolases;Phenotype;Phospholipids;Physiological;Pilot Projects;Plasma;Plasma Proteins;Plasmin;Plasminogen;posttranscriptional;Process;Property;Protein Secretion;protein transport;Proteins;Proteomics;receptor;Receptor Activation;receptor mediated endocytosis;Regulation;Reporting;Research;Resolution;response;Ribonucleases;Ribonucleoproteins;RNA;RNA delivery;Role;Serine Protease;Small RNA;System;Testing;Tissues;TLR7 gene;TLR8 gene;Transfer RNA;Untranslated RNA;uptake;Viral

PROJECT_TITLE: Novel functions of plasminogen and its diverse cargo in blood

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ADMINISTERING_IC: HS

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: SAN ANTONIO

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: PROJECT NARRATIVE The study is essential for understanding the influence of social determinants of health (SDH) on post-acute care (PAC) rehabilitation access and variation in quality-of-care outcomes across the nation. This project will evaluate SDH variables and their association with PAC access across PAC settings, across rural and urban rehabilitation service areas, and how these associations are moderated by racial and ethnic population density and the COVID pandemic as well as how these factors impact readmission and successful community discharge outcomes. The study informs clinicians, researchers, communities, policy debates, and can lead to better PAC outcomes, and allow us to better understand SDH factors that affect quality-of-care.

PI_NAMEs: REISTETTER, TIMOTHY  (contact)

PROGRAM_OFFICER_NAME: ZHANG, XINZHI

PROJECT_TITLE: Evaluation of Post-Acute Care Access and Outcomes: Influence of Social Determinants of Health on Urban and Rural Rehabilitation Service Areas Before and After COVID-19

STUDY_SECTION: HEOR

STUDY_SECTION_NAME: Healthcare Effectiveness and Outcomes Research[HEOR]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_DEPT: BIOLOGY

PHR: Intervertebral disc disorders and back pain are linked to senescence, which contributes to back pain through the expression of an array of molecules. We have discovered a novel protein that directly regulates this process and has the potential to improve our understanding of back pain development and has potential to be utilized as a novel treatment target.

PI_NAMEs: BOWLES, ROBERT D. (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Address;Back Pain;Biology;Cell Cycle;Cell Physiology;Cell Therapy;cell type;Cells;cellular engineering;ChIP-seq;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR interference;CRISPR-mediated transcriptional activation;Data;Deposition;Development;Disease;Engineering;experimental study;Gene Activation;Gene Chips;Gene Modified;Gene Targeting;gene therapy;Genes;Genetic;Genome;Grant;Growth Factor;Health;Human;Human Engineering;Immunoprecipitation;improved;in vivo;Intervertebral disc structure;intervertebral disk degeneration;Link;Maintenance;Mass Spectrum Analysis;Mechanics;Modeling;Musculoskeletal;Musculoskeletal Diseases;Neurons;novel;Outcome;Phenotype;Play;Process;Production;Proteins;Publications;Puncture procedure;Rattus;Repression;Research;RNA Transport;Role;senescence;senescence associated secretory phenotype;senescent cell;Sequence Analysis;stem cells;subcutaneous;T-Lymphocyte;Therapeutic;therapy outcome;Tissue Engineering;Tissues;tool;transcription factor;transcriptome sequencing;Up-Regulation;vector;Zinc Fingers

PROJECT_TITLE: Novel Zinc-Finger Protein Regulator of Senescence and Cell Engineering

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

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

NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Estrogen;Infertility;Women's Health Research

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Project Narrative The proposed research is relevant to public health because preimplantation uterine fluid regulation is crucial for several early pregnancy events and its dysregulation can lead to two important public health problems: infertil- ity and early pregnancy loss. This proposal aims to investigate mechanisms for the temporal uterine fluid ab- sorption during early pregnancy in mouse models and human endometrium under physiological and pathologi- cal conditions. Understanding mechanisms in regulating uterine fluid absorption during early pregnancy will fill in a knowledge gap and provide novel information for future development of approaches to manage uterine fluid to facilitate successful early pregnancy.

PI_NAMEs: SEGARS, JAMES H.;XIAO, SHUO ;YE, XIAOQIN  (contact)

PROGRAM_OFFICER_NAME: JOHNSTON, DANIEL STEPHEN

PROJECT_TERMS: 3-Dimensional;absorption;Amiloride;Animal Model;Architecture;Area;Atlases;Biopsy;Black Box;Cell membrane;Coculture Techniques;Coitus;Cystic Fibrosis Transmembrane Conductance Regulator;Data;Development;early pregnancy;early pregnancy loss;Embryo Transfer;Endometrial;endometrial organoid;endometriosis;Endometrium;Engineering;Epithelial Cells;epithelial Na+ channel;Epithelium;ESR1 gene;Estradiol;Estrogens;Event;experience;Extracellular Space;failure Implantation;female reproductive tract;Fertilization;Fertilization in Vitro;Future;Gene Expression;Goals;Gonadal Steroid Hormones;Hormonal;Human;human model;Impairment;implantation;improved;In Vitro;in vivo;Infertility;infertility treatment;Ion Channel;Ions;Knowledge;Light;Liquid substance;Mammalian Oviducts;Membrane;Menstruation;Methods;Microfluidics;microphysiology system;migration;Molecular;mouse model;Movement;mRNA sequencing;Mus;natural Blastocyst Implantation;novel;Organoids;Osmosis;Ovarian;Ovarian Follicle;Ovarian hormone;Ovarian Stimulations;Ovulation;Pathologic;Pathway interactions;Patient Transfer;pharmacologic;Phase;Physiological;preimplantation;Progesterone;Progesterone Receptors;Public Health;Receptor Signaling;Regulation;Reproduction;Research;Risk;Role;sperm cell;success;System;Testing;therapy design;Transgenic Mice;uterine receptivity;Uterus;Visualization;water channel;Water Movements;Woman

PROJECT_TITLE: Mechanisms of uterine fluid absorption during early pregnancy

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Clinical Research;Clinical Trials and Supportive Activities;Emphysema;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Orphan Drug;Rare Diseases

ORG_DEPT: GENETICS

PHR: Narrative. Alpha 1-antitrypsin (AAT) deficiency is a hereditary disorder associated with the early onset of emphysema. AAT normally protects the lung from inflammatory enzymes capable of destroying the lung parenchyma. We propose to treat AAT deficiency with a single administration of AAV8hAAT(AVL), a gene therapy that codes for a modified form of AAT that is resistant to oxidant inactivation, which if safe and efficacious, and will protect the lung on a persistent basis.

PI_NAMEs: CRYSTAL, RONALD G (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Acceleration;Active Sites;adeno-associated viral vector;Air Pollutants;Alanine;Alleles;Allergic Reaction;alpha 1-Antitrypsin;alpha 1-Antitrypsin Deficiency;Alveolus;autosome;Biological;C57BL/6 Mouse;Cells;cigarette smoke;Circulation;Clinical;Clinical Research;Clinical Trials;Code;cohort;Data;Diffusion;Disease;Dose;Drug Packaging;early onset;efficacy study;Engineering;Enrollment;Ensure;Enzymes;Epithelium;gene therapy;Genes;Genome;Hepatocyte;Hereditary Disease;Homozygote;Human;In Vitro;in vivo;Individual;Inflammatory;Infusion procedures;Institutional Review Boards;intravenous administration;Investigational Drugs;Leucine;Leukocyte Elastase;Liquid substance;Liver;Lung;manufacture;manufacturing process;Methionine;Methods;Mus;Mutation;neutrophil;oxidant stress;Oxidants;oxidation;parenteral administration;Peptide Hydrolases;Phase;phase 1 study;Phase I Clinical Trials;Plasma;plasma protein Z;Polymers;pre-Investigational New Drug meeting;preclinical efficacy;preclinical safety;preclinical study;Predisposition;Production;Protease Inhibitor;Proteins;Protocols documentation;Pulmonary Emphysema;pulmonary function;Quality Control;Reporting;Resistance;Risk;Running;Safety;safety assessment;Serine Protease;Serine Proteinase Inhibitors;Serotyping;Serum;Smoking;Structure of parenchyma of lung;Testing;Therapeutic;Toxic effect;Toxicology;Translating;Valine;Variant;Viral

PROJECT_TITLE: Gene Therapy for Alpha 1-Antitrypsin Deficiency

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-F (J2)]


NIH_SPENDING_CATS: Cardiovascular

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Hundreds of mutations to the LMNA gene, which encodes the Lamin A/C proteins, have been linked to more than 10 distinct syndromes, collectively referred to as “laminopathies”. We present evidence that modulation of protein lifetime is a major novel axis that regulates both the function of Lamin A/C and the effects of laminopathy mutations and will test predictions of this model in mouse models of laminopathy diseases.

PI_NAMEs: BUCHWALTER, ABIGAIL LYNN (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: Address;Affect;age acceleration;Binding;Biochemical;bone;Cardiovascular Diseases;Cardiovascular system;Cell Nucleus;citrate carrier;Connective Tissue;Cultured Cells;Data;Development;Disease;Emery-Dreifuss Muscular Dystrophy;Environment;experimental study;Fatty acid glycerol esters;Filament;Genes;Genome;genome integrity;Genotype;Goals;Health;Heterochromatin;human disease;Impairment;In Situ;in vivo;Intermediate Filament Proteins;Label;lamin C;Lamin Type A;Lamins;Letters;Link;Maps;Mass Spectrum Analysis;Mechanics;Metabolic;mouse model;Muscle;mutant;Mutation;novel;Nuclear;Nuclear Envelope;Nuclear Lamin;Nuclear Matrix-Associated Proteins;Phenotype;Physiological;Polymers;predictive modeling;Production;Progeria;programs;protein degradation;protein folding;protein function;Protein Isoforms;Proteins;Proteolysis;Proteome;Proteomics;Regulation;Research;scaffold;Skeletal Muscle;Skin;Solubility;Structural Protein;Structure;Syndrome;Techniques;Tertiary Protein Structure;Testing;Time;Tissues

PROJECT_TITLE: Exploring modulation of Lamin A/C protein lifetime as a novel axis of regulation in heath and disease

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


NIH_SPENDING_CATS: Behavioral and Social Science;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;Mental Health;Prevention;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE Intimate partner violence is experienced by one-fourth of women globally and linked to poor mental, physical, sexual, and reproductive health, thus underscoring the need for innovative, effective strategies to prevent intimate partner violence. The proposed study examines the impact of a couples-based intervention, “Ghya Bharaari Ekatra,” in preventing intimate partner violence and enhancing reproductive autonomy and mental health among newly married couples in India. The study will provide critical insight on the efficacy of the intervention, its mechanism of effect, contexts that may modify its effects, and the barriers, facilitators, and strategies for its successful future adoption and implementation, thereby enabling rapid scale-up of the intervention across India and similar resource-limited, high-burden settings globally upon study completion.

PI_NAMEs: BEGUM, SHAHINA ;KALOKHE, AMEETA SHIVDAS (contact);SAHAY, SEEMA

PROGRAM_OFFICER_NAME: POPKIN, RONNA

PROJECT_TERMS: Acquaintances;Address;Adoption;Adverse event;Age;behavior change;Cluster randomized trial;Communication;Communities;community based participatory approach;comparison intervention;Conflict (Psychology);Consolidated Framework for Implementation Research;cost;Couples;design;Development;efficacy evaluation;Enrollment;Ethics;evidence base;experience;Female;Future;gender-based violence;health knowledge;Health Resources;Healthcare;Human Rights;implementation facilitators;implementation outcomes;implementation strategy;improved;Income;India;Individual;innovation;insight;Intervention;Interview;intimate partner violence;Joints;Knowledge;Legal;Link;Low income;male;Mediating;Mediation;member;men;Mental Health;Methods;Modification;National Institute of Child Health and Human Development;Nuclear Family;Outcome;Participant;participant retention;peer;physical conditioning;Pilot Projects;prevent;preventive intervention;primary outcome;Primary Prevention;Process;Productivity;Psyche structure;Public Health;Publishing;Qualitative Research;Reporting;reproductive;Reproductive Health;Research;resilience;Resource-limited setting;Resources;Safety;scale up;secondary outcome;Secondary Prevention;self esteem;sexual and reproductive health;Sexual Health;Shelter facility;skills;Slum;social norm;Social support;Socioeconomic Status;standard of care;Strategic Planning;tertiary prevention;Testing;theories;Time;Treatment Efficacy;United States National Institutes of Health;violence prevention;Woman;Women's Health;women's reproductive health;World Health Organization

PROJECT_TITLE: Primary Prevention of Intimate Partner Violence

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Lung;Nutrition;Obesity;Physical Activity;Prevention;Pulmonary Hypertension;Rare Diseases

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Patients with pulmonary arterial hypertension (PAH) are at increased risk of muscle loss and decreased physical activity. This proposal will aim to (1) understand the underlying pathologic mechanisms that contribute to muscle loss in PAH, particularly focusing on the role of the fat surrounding the heart, and (2) assess the impact muscle loss has on quality of life, daily physical activity, and hospitalizations in patients with PAH. Finally, in a small pilot study, we will also explore how a low resistance exercise intervention may improve muscle mass for PAH patients.

PI_NAMEs: AL-NAAMANI, NADINE  (contact)

PROGRAM_OFFICER_NAME: XIAO, LEI

PROJECT_TERMS: Acute;Address;adipokines;adiponectin;Adipose tissue;Aerobic Exercise;Affect;Agonist;Area;Artificial Intelligence;biceps brachii muscle;Body Composition;Cachexia;Cardiac Output;Characteristics;Chest;chest computed tomography;Chronic;Clinic;Clinical;cohort;Complex;cost;Counseling;cytokine;Data;Desire for food;Diagnosis;Diet;dietary;Dietary intake;Dual-Energy X-Ray Absorptiometry;Educational Intervention;endophenotype;Enrollment;Evaluation;Exercise;exercise capacity;exercise intervention;Failure;Fatty acid glycerol esters;fatty acid oxidation;Fatty Acids;Fatty Change;Foundations;Functional disorder;Gastrocnemius Muscle;GLP-I receptor;health related quality of life;Heart;Heart failure;High Prevalence;Hospitalization;hospitalization rates;Hybrids;hypoperfusion;Impairment;improved;indexing;Individual;Inflammation;Inflammatory;insight;insulin sensitivity;Intervention;Intervention Trial;Intestines;Knowledge;Lead;Left;Low Prevalence;Lung;Measurement;Measures;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methods;Morbidity - disease rate;mortality;Muscle;muscle form;muscle strength;Muscular Atrophy;Near-Infrared Spectroscopy;novel;nutrition;obese person;Obesity;Organ;Outcome;Oxygen;Pathogenesis;Pathologic;Pathway interactions;Patient-Focused Outcomes;Patients;personalized intervention;Physical activity;Physiological;Pilot Projects;Play;Prognosis;Progressive Disease;prospective;Prospective cohort;Prospective, cohort study;pulmonary arterial hypertension;Pulmonary Hypertension;pulmonary vascular disorder;Quality of life;radiological imaging;Recommendation;Reference Standards;Resistance;resistance exercise;Respiratory Muscles;response;Right Ventricular Dysfunction;Risk;Role;routine care;Scanning;screening;Skeletal Muscle;Techniques;Texture;Therapeutic;Thinness;Thoracic cavity structure;Time;Training;Transplantation;Validation;Visceral;Weight

PROJECT_TITLE: Unraveling the systemic manifestations of pulmonary arterial hypertension on lean muscle mass

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Brain Disorders;Emerging Infectious Diseases;Infectious Diseases;Neurosciences;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BOSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Alphaviruses are viruses that are spread by mosquitoes and can cause outbreaks of severe brain infections with no approved drugs or vaccines available to combat them. Recently, we identified three proteins that are expressed on brain cells as specific host cell receptors for alphaviruses that cause encephalitis in both horses and humans. Our research aims to visualize how alphaviruses attach to these receptors and to test the importance of receptor interactions to the ability of the viruses to cause brain infections with implications for therapeutic targeting.

PI_NAMEs: ABRAHAM, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Address;Alpha Virus;Alphavirus Infections;alphavirus receptor;Americas;Anti-viral Agents;apolipoprotein E receptor 2;Astrocytes;Binding;Binding Proteins;Biochemical;Biological Assay;Brain;brain cell;Case Fatality Rates;cell type;Cells;climate change;combat;Cryoelectron Microscopy;Culicidae;Dependence;design;Disease;Disease Outbreaks;Drug or chemical Tissue Distribution;Eastern Equine Encephalitis Virus;Eastern Equine Encephalomyelitis;Encephalitis;epidemic potential;Equus caballus;experimental study;FDA approved;Human;human pathogen;In Vitro;Infection;inhibitor;insight;Knowledge;Left;Low-Density Lipoproteins;Membrane Proteins;Microglia;Mus;Nervous System Trauma;Neurons;Neuropathogenesis;Pathogenesis;Pathogenicity;Pathway interactions;Pharmaceutical Preparations;Physiological;prevent;Property;Proteins;protocadherin 10;Public Health;receptor;receptor binding;Receptor Cell;Research;Resolution;RNA Viruses;Role;Secondary to;Structure;Testing;Therapeutic Intervention;therapeutic target;Time;Tissues;transmission process;unpublished works;vaccine access;Vaccines;Venezuelan Equine Encephalitis Virus;Viral Encephalitis;Viral Pathogenesis;Virulence;Virus;Virus Diseases;Virus Receptors;Virus-like particle;Visualization;VLDL receptor;Western Equine Encephalitis Virus;Western Equine Encephalomyelitis;Work

PROJECT_TITLE: Structural and functional studies of alphavirus receptors

STUDY_SECTION: VDT

STUDY_SECTION_NAME: Viral Dynamics and Transmission Study Section [VDT]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_DEPT: NEUROLOGY

PHR: NARRATIVE While new brain stimulation therapies are now available for temporal lobe epilepsy patients who do not respond to drug therapy, the antiepileptic effects are very variable between patients. There is then a clear need to better understand the propagation and control network to develop more efficient individualized therapies. We are proposing to investigate the implication of the basal ganglia in the propagation and control of temporal lobe seizures and how the seizure onset pattern affects this propagation network.

PI_NAMEs: DEVERGNAS, ANNAELLE  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Affect;Agonist;Anatomy;Animal Model;Animals;anti-epileptic agents;Area;Attention;Basal Ganglia;Brain;Cell Separation;Cells;Characteristics;Chemicals;Data;Deep Brain Stimulation;Dopamine;Dopamine Agonists;Electrophysiology (science);Eligibility Determination;Epilepsy;Etiology;Exhibits;experimental study;Frequencies;Globus Pallidus;Heterogeneity;High Frequency Oscillation;Human;Image;Impact Seizures;improved;individualized medicine;Injections;Intractable Epilepsy;Label;Maintenance;Measures;Medical;Metabolic;Modeling;Neurons;Nodal;nonhuman primate;novel therapeutics;Nucleus Accumbens;Operative Surgical Procedures;Output;Partial Epilepsies;Pathway interactions;patient variability;Patient-Focused Outcomes;Patients;Pattern;Penicillins;pharmacologic;Pharmacotherapy;Prediction of Response to Therapy;Primates;putamen;Qualifying;receptor;response;Role;Seizures;Structure;Substantia nigra structure;System;Temporal Lobe;Temporal Lobe Epilepsy;therapy development;Treatment outcome;Work

PROJECT_TITLE: Impact of seizure onset pattern on temporal lobe seizure propagation through the basal ganglia

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


NIH_SPENDING_CATS: Clinical Research;Eye Disease and Disorders of Vision

ORG_DEPT: PEDIATRICS

PHR: NARRATIVE Dry eye disease (DED) is a major health problem, however current treatments have variable and limited efficacy. Extracellular Ca2+-sensing receptor (CaSR) is a modulator of ocular surface fluid transport and promising drug target for DED treatment. This proposal aims to develop CaSR inhibitors as novel treatment candidates for DED, and to study the roles and mechanisms of CaSR in ocular surface health.

PI_NAMEs: CIL, ONUR  (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Adult;Affect;Agonist;Animal Disease Models;Animal Diseases;Animal Model;Animals;Anti-Inflammatory Agents;aqueous;Artificial Tears;Calcium-Sensing Receptors;Cell model;Cells;Clinical;Clinical Trials;clinically relevant;conjunctiva;Conjunctival Epithelium;Cornea;corneal epithelium;Cyclic AMP;Cystic Fibrosis Transmembrane Conductance Regulator;Data;Disease;Dose;drug candidate;Drug Targeting;Dry Eye Syndromes;effective therapy;efficacy testing;Epithelial Cells;Epithelium;Excision;experimental study;extracellular;Eye;Eyedrops;FDA approved;Film;Fluids and Secretions;Fluorescein;Frequencies;Future;Goals;Health;Histology;Human;Hydration status;Hydrolysis;Impairment;In Vitro;Inflammation;inflammatory marker;inhibitor;intestinal epithelium;Intestines;Investigational Drugs;Ion Channel;Ion Transport;Kidney;Lacrimal gland structure;Liquid substance;Lung;Measures;Mediating;Modeling;Molecular;Morbidity - disease rate;mouse model;Mus;novel;ocular surface;Oryctolagus cuniculus;Osmolar Concentration;overexpression;Pathology;Patient Compliance;Patients;Physiological;protein expression;Receptor Activation;receptor expression;Receptor Inhibition;research clinical testing;Role;Safety;Signal Pathway;Signaling Molecule;Stains;Stress;Symptoms;targeted agent;Techniques;Testing;Therapeutic;Tissues;Toxic effect;translational study;Western Blotting

PROJECT_TITLE: Roles of CaSR in ocular surface health and disease

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Immunotherapy;Nanotechnology;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: This project will develop a non-invasive imaging agent to detect inflammatory cells associated with head and neck cancers. This agent will be used to measure the inflammation severity at tumor sites using magnetic resonance imaging (MRI). This imaging technology will enhance our ability to personalize cancer treatments.

PI_NAMEs: AHRENS, ERIC T. (contact);CALIFANO, JOSEPH A

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: angiogenesis;Animals;anti-PD-1;anti-PD-L1;anti-PD1 antibodies;Antibodies;Antitumor Response;Biodistribution;Biological Assay;Biological Markers;Biopsy;Blood Substitutes;cancer imaging;Cancer Model;Cancer Patient;cancer therapy;Cd68;Cells;checkpoint therapy;Clinic;Clinical;Clinical Research;Clinical Trials;Collaborations;colon cancer patients;Contracts;CTLA4 gene;Data;density;Detection;Diagnosis;Diagnostic;Disease;Disease Progression;Drug Kinetics;Endocytosis;Excipients;Exclusion;experience;first-in-human;Fluorine;Fluorocarbons;Formulation;Future;genotoxicity;Goals;good laboratory practice;Good Manufacturing Process;Growth;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Histologic;Human;Image;imaging agent;imaging probe;imaging study;Imaging technology;Immune;immune checkpoint;Immune checkpoint inhibitor;Immunosuppression;Immunotherapeutic agent;Immunotherapy;improved outcome;In Situ;In Vitro;in vivo;Inflammation;Inflammatory;Injectable;intravenous administration;intravenous injection;Label;Lead;Lesion;Macrophage;Magnetic Resonance Imaging;Malignant Neoplasms;Manufacturer;manufacturing organization;Measures;Modeling;monocyte;Morphology;nanoemulsion;non-invasive imaging;non-invasive monitor;novel;objective response rate;Oils;Oncology;Outcome;Oxygen;patient population;patient stratification;Patients;personalized cancer therapy;personalized therapeutic;Phagocytes;Pharmacologic Substance;phase I trial;Pilot Projects;Play;pre-clinical;preclinical imaging;preclinical study;Predisposition;Prognosis;prognostic;programmed cell death ligand 1;Progression-Free Survivals;Recurrence;response;Reticuloendothelial System;Role;Safety;Severities;Signal Transduction;Site;Solid Neoplasm;Specificity;Stains;standard of care;surfactant;T-Lymphocyte;Technology;Therapeutic;therapeutic target;therapy outcome;Tracer;Translating;treatment response;tumor;tumor microenvironment;Tumor Volume;Tumor-associated macrophages;uptake;Vesicle;Visualization;Work

PROJECT_TITLE: Imaging tumor-associated macrophages in head and neck squamous cell carcinoma using fluorine-19 MRI

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Hematology;Human Genome;Neurodegenerative;Neurosciences;Prevention;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PHR: Project Narrative Alzheimer’s Disease (AD) is the most prevalent cause of dementia and the most common age-related neurodegenerative disorder. We showed in the mouse model of AD that transplantation of bone marrow hematopoietic stem cells (HSCs) that give rise to blood cells, holds great promise to treat AD, by differentiation of the transplanted HSCs into microglia (type of immune cells in the brain). This approach fully rescued AD complications including neurocognition decline and neuroinflammation, but the mechanism of rescue is still unknown, and the objective of this application is to understand the mechanism of the beneficial impact of wildtype HSCs.

PI_NAMEs: CHERQUI, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: abeta accumulation;Affect;Age Months;age related neurodegeneration;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid Beta A4 Precursor Protein;Amyloid beta-Protein Precursor;ATAC-seq;Behavior;Behavioral;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Cells;Blood Preservation;blood-brain barrier disruption;Bone Marrow Transplantation;Brain;causal variant;Cell Lineage;Cells;CRISPR/Cas technology;Data;Dementia;Development;Disease;disease phenotype;Disease Progression;Endothelial Cells;Engraftment;epigenomics;Exhibits;extracellular;Genes;Genetic Predisposition to Disease;Gliosis;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Hippocampus;Human;hyperphosphorylated tau;Immune;Impaired cognition;improved;Inflammation;Inflammatory;Knock-out;Memory;Microglia;Modeling;Motor Activity;mouse model;Mus;mutant;Mutate;Neurocognition;Neurocognitive;Neurofibrillary Tangles;neuroinflammation;Neurons;Onset of illness;Pathogenesis;Pathway interactions;Pattern;Performance;peripheral blood;Peripheral Blood Mononuclear Cell;Persons;Phenotype;Play;presenilin-1;preservation;prevent;Prevention;Regulatory Element;Rest;Role;Senile Plaques;Testing;Therapeutic;Therapeutic Effect;Time;transcriptome sequencing;transcriptomics;Transgenic Mice;Transplantation;Wild Type Mouse;Work

PROJECT_TITLE: Understanding the mechanism of rescue of Alzheimers disease by hematopoietic stem cell transplantation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-Z (55)]


ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: NARRATIVE Transthyretin cardiac amyloidosis is a prevalent form of heart failure that is underdiagnosed and underappreciated. Because this condition predominantly occurs in elderly men, this research will explore the role of mosaic loss of the Y chromosome in the etiology of this disease.

PI_NAMEs: WALSH, KENNETH  (contact)

PROGRAM_OFFICER_NAME: GAO, HONGWEI

PROJECT_TERMS: accurate diagnosis;Acute;Address;Adverse event;aging process;Amyloid;Amyloid deposition;Amyloid Fibrils;Amyloidosis;Animal Model;Autopsy;Biological Markers;Biological Models;Biopsy;Blood;Blood capillaries;Bone Marrow;Cardiac;cardiac amyloidosis;Cardiac Myocytes;Cardiology;Cardiovascular Diseases;Cells;chromosome Y loss;Classification;Clinical;cohort;Collecting Cell;Data Set;Death Rate;density;Diagnosis;differential expression;digital;Disease;DNA;Echocardiography;EFRAC;Elderly;Elderly man;epidemiology study;Etiology;experimental study;Female;Fibrosis;Flow Cytometry;Functional disorder;Genes;Genotype;Heart;Heart failure;heart function;Hematopoietic;Hematopoietic System;Histology;Human;immune cell infiltrate;Incidence;indexing;Individual;intercellular communication;Life Expectancy;life span;Liver;Magnetic Resonance;male;Mass Spectrum Analysis;Measurement;Molecular;mortality;mosaic loss;mouse model;Mus;mutant;Mutation;nuclear imaging;Ontology;Outcome;Pathway interactions;patient population;Patient Recruitments;Patients;Periodicals;Peripheral Blood Mononuclear Cell;population based;Prealbumin;preservation;Prevalence;Process;Prognosis;prognostic significance;Proteins;Recombinants;Reporting;Research;RNA Sequence Analysis;Role;Sampling;Science;Secondary to;Sex Bias;Surveys;System;Testing;Time;transcriptome;transcriptomics;Transgenic Mice;Universities;Variant;Virginia;Wild Type Mouse;Work;Y Chromosome

PROJECT_TITLE: Mosaic Loss of the Y Chromosome in Cardiac Amyloidosis

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: NARRATIVE Drugs that inhibit mutant forms of the metabolic enzyme isocitrate dehydrogenase (IDH) enzymes were recently approved as therapies for some leukemias and solid tumors. However, inhibiting mutant IDH enzymes helps less than half of patients with IDH-mutant cancers, and drug resistance invariably develops. The proposed research investigates the surprising discovery that hyperactivation, rather than inhibition, of mutant IDH enzymes might offer a more effective strategy to treat IDH-mutant cancers.

PI_NAMEs: INTLEKOFER, ANDREW MICHAEL (contact)

PROGRAM_OFFICER_NAME: GREENBERG, WILLIAM A

PROJECT_TERMS: Active Sites;Acute Myelocytic Leukemia;Alleles;Biochemical;Biochemistry;Biological Assay;cancer cell;Cancer Model;Cell Proliferation;Cells;Chemicals;Cholangiocarcinoma;Chondrosarcoma;Clinical;cofactor;Consumption;Data;Dependence;Development;dimer;Drug resistance;Enzyme Induction;Enzyme Inhibition;Enzymes;Evolution;Exhibits;Gene Expression;Genetic;Glioma;Growth;Impairment;In Vitro;in vivo;in vivo Model;inhibitor;Isocitrate Dehydrogenase;leukemia;Leukemic Cell;Malignant Neoplasms;Mediating;Metabolic;Mitochondria;mitochondrial dysfunction;mutant;Mutation;NADH;NADP;Nature;novel;novel therapeutic intervention;Oncogenes;Oncogenic;Patients;Pattern;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Poison;Production;Property;Research;Resistance;resistance mechanism;resistance mutation;response;Shapes;small molecule;Solid Neoplasm;Somatic Mutation;stemness;Structural Models;Structure;T-Cell Lymphoma;Testing;therapeutic target;therapeutically effective;Toxic effect;tumor;tumor metabolism;Work

PROJECT_TITLE: Targeting isocitrate dehydrogenase mutations by enzyme hyperactivation

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


NIH_SPENDING_CATS: Clinical Research;Kidney Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Organ Transplantation;Transplantation

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Narrative In our previous NIDDK-funded CISTEM study, we integrated 3 different types of national databases to determine the impact of kidney transplant immunosuppressive regimens selection on the development of 10 separate efficacy or morbidity outcomes. We now seek to extend our results in CISTEM2 to dynamically optimize long term kidney transplant function through optimal immunosuppression management by integrating multiple transplant center electronic medical records datasets and deploying machine learning algorithms. With input from patient focus groups, we will refine our existing CISTEM web-based decision support tool input to assist transplant recipients and their care teams make more informed and personalized choices to minimize morbidity and extend kidney graft survival.

PI_NAMEs: AXELROD, DAVID ADAM;DHARNIDHARKA, VIKAS R. (contact)

PROJECT_TERMS: Acute;Allografting;Awareness;Caring;Cessation of life;Characteristics;Clinical;Clinical Data;Clinical Research;comorbidity;Complex;computable phenotypes;Computerized Medical Record;cost;cost effective;Cox Proportional Hazards Models;Creatinine;Data;data modeling;data registry;Data Set;Databases;Development;Diabetes Mellitus;Diagnosis;Drops;Ecosystem;Equilibrium;Event;evidence base;experience;Face;Focus Groups;Funding;Glomerular Filtration Rate;graft failure;graft function;Graft Survival;Grant;Great Plains;health data;Healthcare Systems;hospital readmission;Immunosuppression;improved;Infection;Infrastructure;interest;Ischemia;kidney allograft;Kidney Transplantation;Learning;Life;Link;longitudinal dataset;Machine Learning;machine learning algorithm;machine learning model;Malignant Neoplasms;Measures;Medicare claim;Methods;Midwestern United States;model development;Modeling;Morbidity - disease rate;National Institute of Diabetes and Digestive and Kidney Diseases;Network Infrastructure;novel;Online Systems;Organ;Outcome;Outcome Measure;patient oriented;Patients;Pharmaceutical Preparations;Pharmacy facility;Phenotype;Physicians;Pneumonia;Population;post-transplant;Practice Management;predictive modeling;Psychological reinforcement;Quality of life;Regimen;Registries;Rewards;Risk;Sampling;Secure;Sepsis;Serum;shared decision making;Site;social health determinants;Statistical Data Interpretation;Structural Models;support tools;Tacrolimus;Time;tool;transplant centers;Transplant Recipients;transplant registry;Transplantation;United States;Urinary tract infection;Validation;Viremia;web based interface;Work

PROJECT_TITLE: Choosing Immune Suppression in Renal Transplantation by Efficacy and Morbidity2 (CISTEM2)

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative We will perform a series of experiments to investigate the mechanisms and application of myelin formation in regenerated axons from retinal ganglion cells in the visual pathways. The obtained results should provide direct insights into developing the therapeutic strategies of promoting myelination and neural repair after trauma and diseases. 1

PI_NAMEs: HE, ZHIGANG  (contact)

PROGRAM_OFFICER_NAME: FORTRESS, ASHLEY

PROJECT_TERMS: Ablation;Address;Affect;Astrocytes;Axon;axon injury;axon regeneration;Behavior;Behavioral;behavioral outcome;Cell Death;Cell Differentiation process;cell type;Cells;Central Nervous System Diseases;Chemicals;Clinical;Communication;Demyelinations;Disease;Dissection;druggable target;experimental study;Failure;functional outcomes;G-Protein-Coupled Receptors;Glaucoma;GPR17 gene;improved;Individual;Inflammation;inflammatory milieu;inhibitor;Injury;insight;Intervention;Knock-out;Knockout Mice;Mediating;method development;Microglia;Modeling;Molecular;Molecular Profiling;Multiple Sclerosis;Mus;Muscarinic Acetylcholine Receptor;Myelin;myelination;Natural regeneration;Nerve Crush;Nervous System;neural repair;neurotensin mimic 1;oligodendrocyte progenitor;Oligodendroglia;Optic Nerve;Optic Nerve Injuries;Optic tract structure;Pathway interactions;Pilot Projects;precursor cell;prevent;Proliferating;Protein Kinase Interaction;receptor;Receptor-Interacting Protein;regenerative;response;response to injury;restoration;Retina;retinal ganglion cell regeneration;Retinal Ganglion Cells;Series;sight restoration;Signal Pathway;Signaling Molecule;single-cell RNA sequencing;superior colliculus Corpora quadrigemina;Testing;Therapeutic;Thinness;TNF gene;TNFRSF1A gene;Trauma;Traumatic CNS injury;Vision;Visual;Visual Acuity;Visual Pathways;Work

PROJECT_TITLE: Promoting myelination of regenerating axons for vision restoration

STUDY_SECTION: CMBG

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


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: CHICAGO

ORG_NAME: LURIE CHILDREN'S HOSPITAL OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative Although numerous large studies have been done to demonstrate that structural variants (SVs) are important for brain tumor diagnosis and management, the full spectrum of SVs within pediatric brain tumors is not fully characterized and a clinical test that can rapidly and accurately identify all clinically relevant SVs is absent. In this study, we will work with Augusta University and Bionano Laboratories to validate and develop optical genome mapping, a method that uses ultra-high molecular weight DNA to identify SVs, as a clinical test for pediatric brain tumors and concurrently discover novel SVs in a large cohort of 1000 brain tumor samples. The outcomes of this study will provide a pathway for discovery of novel SVs, as well as allow for improved diagnostic, prognostic, and therapeutic management of brain tumors in children.

PI_NAMEs: BARSEGHYAN, HAYK ;BORNHORST, MIRIAM A. (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Adult;Affect;Age;American Medical Association;Animal Model;Automobile Driving;Bioinformatics;Biological;Biological Assay;Blinded;BRAF gene;Brain Neoplasms;cancer genome;Certification;Child;Childhood Brain Neoplasm;Clinical;clinical application;clinical care;clinical diagnostics;clinical practice;Clinical Treatment;Clinical Trials;clinically relevant;clinically significant;Code;cohort;Computer software;cost effectiveness;Cost-Benefit Analysis;Custom;Data;Data Analyses;Data Set;Detection;Development;Diagnosis;Diagnostic;diagnostic strategy;Diagnostic tests;diagnostic value;Disease;DNA;DNA Sequence Alteration;Evaluation;Facioscapulohumeral Muscular Dystrophy;Fluorescent in Situ Hybridization;Gender;Gene Expression;Gene Fusion;Genes;Genetic;genetic testing;genetic variant;Genome;Genome Mappings;genomic profiles;Genomics;Guidelines;Hematologic Neoplasms;Histologic;Hospitals;improved;information model;Label;Laboratories;Length;Literature;Maintenance;Malignant Neoplasms;Measures;Medicare;Methods;Molecular;Molecular Abnormality;molecular diagnostics;Molecular Weight;Mutation;novel;novel diagnostics;Oncogenes;Optics;Outcome;outcome prediction;Outcome Study;Pathogenicity;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Pediatric cohort;Pediatric Neoplasm;Play;pre-clinical;prediction algorithm;Procedures;prognostic;Progression-Free Survivals;Race;Recommendation;Reproducibility;Research;research clinical testing;research study;RNA;RNA Splicing;Role;Running;Sampling;Series;Somatic Mutation;Southern Blotting;Specificity;standard of care;Stratification;Technology;Testing;Therapeutic;therapeutic development;Therapeutic Uses;Time;transcriptome sequencing;Translating;treatment planning;treatment response;tumor;tumor diagnosis;tumor progression;tumorigenesis;Universities;Validation;Variant;Work

PROJECT_TITLE: Optical Genome Mapping As a Novel Diagnostic Approach in Pediatric Brain Tumors

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 TCRB-9 (J1)]


NIH_SPENDING_CATS: Digestive Diseases;Liver Disease;Organ Transplantation;Regenerative Medicine;Transplantation

ORG_CITY: RALEIGH

ORG_DEPT: OTHER CLINICAL SCIENCES

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: This project seeks to improve both graft preservation and transplant outcomes, to expand the feasibility of transplantation as a treatment for intestinal failure patients. The team will advance donor organ preservation strategies that limit ischemia reperfusion injury and enhance our understanding of the complex interactions between graft immune factors and epithelial barrier integrity. This research will also apply novel technologic platforms to evaluate intestinal viability and barrier function in real-time.

PI_NAMEs: GONZALEZ, LIARA M (contact)

PROGRAM_OFFICER_NAME: KEHN, PATRICIA J

PROJECT_TERMS: 3-Dimensional;adaptive immune response;Address;Allografting;Anti-Inflammatory Agents;Architecture;Biological Assay;Biological Markers;Blood;Blood Vessels;Cell Culture Techniques;Child;Clinical;Clinical Research;Complex;Cryopreservation;Data;electric impedance;Emotional disorder;Enterobacteriaceae;Epithelial Cells;Epithelium;Experimental Models;Failure;Family suidae;Flushing;gastrointestinal transplantation;graft failure;Health;Heart Transplantation;high risk;Histologic;Homologous Transplantation;Hour;Human;immune activation;Immunologic Factors;improved;in vivo Model;Incidence;Individual;infection risk;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Bowel Diseases;Injury;Innate Immune Response;Interleukin-6;intestinal injury;Intestinal permeability;Intestines;Ischemia;Length;Liquid substance;Liver diseases;liver transplantation;Lung Transplantation;Measures;Mediating;Metabolic;Methods;Mucous Membrane;Natural regeneration;Necrotizing Enterocolitis;neuropsychiatric disorder;new technology;novel therapeutics;Organ Donor;Organ Preservation;Organoids;Outcome;Parenteral Nutrition;Patients;Perfusion;Permeability;Personal Satisfaction;porcine model;Positioning Attribute;post-transplant;preservation;Process;Production;Quality of life;regeneration potential;Reperfusion Injury;Reperfusion Therapy;Research;Severities;single-cell RNA sequencing;Small Intestines;standard of care;stem cells;success;Syndrome;Systemic infection;Technology;technology platform;Testing;Therapeutic;Tight Junctions;Time;time interval;Tissue Donors;Tissues;Transplantation;Trauma;Treatment Failure;Warm Ischemia

PROJECT_TITLE: Mitigating Ischemia-Reperfusion Injury to Reduce Early Damage to Intestinal Allografts

STUDY_SECTION: DNPD

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Hematology;Machine Learning and Artificial Intelligence;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF HOUSTON

PHR: PROJECT NARRATIVE Histopathologic examination of annual bone marrow (BM) biopsies, the current standard for myelofibrosis (MF) treatment response assessment, requires three years to identify the post-treatment non-responders reliably. Our goal is to reduce this assessment timeframe to six months in order to improve health outcomes by allowing MF patients to pursue alternative therapies earlier than is currently possible. We propose an integrated histology approach that leverages quantitative molecular imaging to identify biomarkers correlated with the patient’s treatment responsiveness.

PI_NAMEs: REDDY, ROHITH  (contact)

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: Address;Aftercare;Alternative Therapies;Architecture;Archives;Area;biomarker identification;Biopsy;Bone Marrow;Bone marrow biopsy;bone visualization;breast cancer progression;Cells;Chemicals;Clinical;Clinical assessments;clinical care;Clinical Research;Clinical Treatment;Collagen Type I;Couples;Data;Data Analyses;Deterioration;Disease;Disease Progression;Dyes;Early Diagnosis;Early identification;Early treatment;Evaluation;Evolution;Fiber;Fibrosis;Goals;Grain;Health;Hematopoiesis;Hematopoietic;hematopoietic tissue;high risk;Histologic;Histology;histopathological examination;Histopathology;Human;Image;Imaging technology;improved;indexing;inhibitor;Institutional Review Boards;instrument;instrumentation;Interobserver Variability;Interruption;JAK2 gene;Label;Machine Learning;Maps;Measurement;Measures;Methods;Molecular;molecular imaging;Monitor;Morphology;Myelofibrosis;Nature;new technology;Noise;novel therapeutics;Outcome;Patient Care;Patients;Pattern;Pharmaceutical Preparations;Predisposition;Process;Property;Pump;Quality of life;Quantitative Evaluations;Recommendation;Recovery;Research;Research Personnel;Resolution;Reticulin;Sampling;Series;Signal Transduction;spatiotemporal;spectroscopic imaging;Speed;Stains;substantia spongiosa;Survival Rate;Technology;Time;time use;Tissues;treatment guidelines;treatment response;trend;tumor;Validation;Variant;Visual;Visualization;Work

PROJECT_TITLE: Early detection of treatment response in myelofibrosis by polarization-sensitive mid-infrared spectroscopic imaging

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Neurosciences;Nutrition;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: AUGUSTA

ORG_DEPT: NEUROSCIENCES

ORG_NAME: AUGUSTA UNIVERSITY

PHR: NARRATIVE Trauma, infection, and cancer treatments can cause taste buds to degenerate, leading to taste deficits that negatively affect nutrition and quality of life. Taste buds have the potential to regenerate, but we need a better understanding of mechanisms that direct this process in adults. The proposed studies will test injury-induced activation of interleukin (IL-1) and tumor necrosis factor (TNF)-α signaling in specific cell types to promote taste bud regeneration and the recovery of taste function.

PI_NAMEs: MCCLUSKEY, LYNNETTE MARIE (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: Adult;Affect;Animal Model;Anterior;Axon;Axotomy;Brain;cancer therapy;cell type;Cells;chorda tympani;Complex;cytokine;Cytokine Receptors;Cytokine Signaling;Dental;Development;Disease;Distal;Ear;Epithelium;Family;Functional disorder;Goals;Growth Factor;Human;IL1R1 gene;Immune;immune cell infiltrate;Immune response;Immune system;Immunologics;Infection;Inflammatory;injured;Injury;insight;Interleukin Activation;Interleukin-1;Interleukin-1 beta;Interleukins;Knockout Mice;long term recovery;Mediating;Molecular;Morphology;Mus;Natural regeneration;Nerve;Nerve Regeneration;nerve supply;Nervous System;neural;Neuroimmune;Neuroimmunomodulation;neurophysiology;Nuclear;nutrition;Otologic Surgical Procedures;p65;Peripheral;Population;prevent;Procedures;Process;Proliferating;Quality of life;receptor;Receptor Cell;Receptor Signaling;Receptors, Tumor Necrosis Factor, Type II;Recovery;Recovery of Function;regenerative;reinnervation;response;response to injury;Role;Signal Transduction;stem cell proliferation;Structure;System;Taste Buds;Taste Perception;taste stimuli;taste system;Testing;Tissues;TNF gene;TNFRSF1B gene;Tongue;Transcription Coactivator;transmission process;Trauma;Tumor Necrosis Factor Receptor;Wild Type Mouse

PROJECT_TITLE: Injury-mechanisms of taste bud regeneration

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-T (02)]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Hematology;Rare Diseases;Sickle Cell Disease

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE Deep vein thrombosis and vaso-occlusive crisis (VOC) are taking a staggering toll on sickle cell disease (SCD) patients. We are taking a new approach based on basic research and advanced technological tools to inhibit the different functions of Factor XII. This approach has a strong potential to inhibit prothrombotic complications as well as attenuate VOC in a safer manner that does not cause bleeding.

PI_NAMEs: PAWLINSKI, RAFAL L (contact);STAVROU, EVI X.

PROGRAM_OFFICER_NAME: PHILP, DEBORAH

PROJECT_TERMS: Address;Adhesions;antagonist;Antibodies;Anticoagulant therapy;Anticoagulation;Attenuated;Basic Science;beta Globin;Binding;Blocking Antibodies;Blood Vessels;Cardiac;Cell Communication;Cells;Chronic;Clinical;Coagulation Process;Deep Vein Thrombosis;Development;Disease;Disease Progression;enhancing factor;Environment;Enzyme Precursors;Event;Exhibits;Factor XII;Factor XII Deficiency;Foundations;Future;General Population;Generations;Genes;Genetic;genetic approach;Goals;Hematological Disease;Heme;Hemolytic Anemia;Hemorrhage;Hepatic;Hypoxia;improved;in vivo;Individual;Integrins;Kidney;Kininogenase;Liquid substance;Liver;Long-Term Effects;Macrophage-1 Antigen;Measures;Mediating;Microfluidics;Molecular;Molecular Conformation;Morbidity - disease rate;mortality;mouse model;multiorgan damage;Mus;Mutation;neutrophil;Neutrophil Activation;novel;novel strategies;novel therapeutic intervention;Nucleotides;Organ;organ injury;Pain;Pathologic;Pathology;Patients;Peptide Hydrolases;Peptide Initiation Factors;Peptides;pharmacologic;Phase;Plasma;prevent;Process;Pulmonary Pathology;receptor;receptor binding;Recombinants;reconstitution;Recurrence;Reporting;Risk;risk minimization;Role;Sampling;Sickle Cell;Sickle Cell Anemia;sickling;Signal Transduction;Site;Source;Surface;System;Technology;Testing;Therapeutic;therapeutic target;Thrombin;thromboinflammation;Thrombophilia;Thrombus;TNF gene;tool;trafficking;Urokinase Plasminogen Activator Receptor;Variant;vaso-occlusive crisis;Venous;Venous Thrombosis;Work

PROJECT_TITLE: Role of Factor XII in Thrombo-Inflammatory Complications of Sickle Cell Disease

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Infectious Diseases;Neurosciences

ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

PHR: PROJECT NARRATIVE Serious ocular infections such as infectious keratitis, uveitis and endophthalmitis are leading causes of blindness globally. Early identification of the causative agent, and prompt initiation of effective therapy, are fundamental to improve outcomes and save vision. This proposal aims to develop a novel and innovative molecular diagnostic approach that can detect approximately 95% of the etiologies of these infections using only one test and with high accuracy, and reduces the time to generate actionable clinical results from days to only 12 hours.

PI_NAMEs: BISPO, PAULO J. M. (contact)

PROJECT_TERMS: accurate diagnosis;Address;Adoption;antimicrobial;Antimicrobial Resistance;biobank;Biological Assay;Blindness;Characteristics;Clinical;Clinical assessments;clinical implementation;Clinical Management;clinically actionable;Collection;Communicable Diseases;Complex Mixtures;Consumption;Cornea;cost;design;Detection;detection assay;Development;Diagnosis;Diagnostic;diagnostic platform;diagnostic strategy;Diagnostic tests;DNA;Early identification;effective therapy;emerging antimicrobial resistance;Endophthalmitis;Equilibrium;Etiology;Eye;Eye Infections;Geography;Goals;Hour;improved;improved outcome;Individual;Infection;innovation;Keratitis;Laboratories;Laboratory Diagnosis;Malignant Neoplasms;Medical center;metagenomic sequencing;Methods;molecular diagnostics;Morbidity - disease rate;nano-string;Noise;novel;novel diagnostics;Nucleic Acids;Ophthalmology;pathogen;Pathogen detection;Patient-Focused Outcomes;Patients;Performance;performance tests;personalized diagnostics;Pharmaceutical Preparations;prospective;Publishing;rapid diagnosis;Reaction;Reporting;repository;Resistance;retinal toxicity;RNA;Sampling;Sensitivity and Specificity;Signal Transduction;Specimen;Speed;Technology;Testing;Time;Tissues;Toxic effect;Translating;Uveitis;Validation;Vision;Work

PROJECT_TITLE: Rapid Diagnosis of Ocular Infections using a Sensitive and Highly Multiplexed Broad Pathogen Detection Assay

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


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision

ORG_CITY: BALTIMORE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Meibomian gland dysfunction is considered the leading cause of dry eye disease, a multifactorial debilitating disease of the ocular surface with a global prevalence ranging from 5 to 50%. This study will elucidate the role of components of the Hedgehog pathway in Meibomian gland development and renewal. It will also define the therapeutic advantage in targeting the Hedgehog signaling cascade using hydrogel-mediated drug delivery systems to counteracting Meibomian gland dysfunction.

PI_NAMEs: IOMINI, CARLO  (contact)

PROJECT_TERMS: Ablation;Acinus organ component;Adult;adult stem cell;Affect;age related;age-related disease;Aging;aging process;Agonist;antagonist;Apoptosis;appendage;Atrophic;Bone Regeneration;Cell Lineage;Cell Maintenance;Cell Physiology;Cells;Cilia;comparative;comparison control;Connective Tissue;Development;Disease;Dropout;Drug Delivery Systems;Drug Formulations;Dry Eye Syndromes;Duct (organ) structure;effective therapy;efficacy evaluation;Ensure;Erinaceidae;evaporation;Eye diseases;Eyedrops;Eyelid structure;Film;Formulation;Functional disorder;Genetic;Gland;gland development;Hair;Hair follicle structure;Homeostasis;Human;human subject;Hydrogels;Impairment;improved;insight;Lipids;Maintenance;Malignant Neoplasms;Mediating;meibomian gland;meibomian gland dysfunction;Molecular;molecular targeted therapies;Morphogenesis;Morphology;Mus;Nature;novel;novel strategies;novel therapeutic intervention;ocular surface;ocular surface disease;old mice;Outcome;Pathogenesis;Pathway interactions;pharmacologic;Play;Prevalence;Process;receptor;Regulation;repaired;Reporter;Reporting;Role;Sebaceous Glands;Signal Transduction;Skin;smoothened signaling pathway;spatiotemporal;stem cells;System;Tarsal plate;Testing;Therapeutic;therapeutic evaluation;therapeutic target;therapeutically effective;Time;Tissues;transcriptomics;translational potential;treatment strategy;United States National Institutes of Health;Vertebrates;Work

PROJECT_TITLE: Functional and therapeutic roles of the Hedgehog signaling in meibomian glands development, renewal and dysfunction


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: NEW YORK

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE The cardiac sarcomere structure is critical for cardiac function and it has been studied extensively with respect to its molecular composition and function during contraction. In contrast, the mechanisms underlying de novo sarcomere assembly early during development, at the stage when many congenital heart defects arise, remain poorly understood. Here we have used an unbiased mass spectrometry approach to determine the alpha-actinin interactome at different stages of cardiac development, from which we will interrogate the molecular mechanisms involved in the z-body to z-disc transition using genetic mouse models and pluripotent stem cell differentiations.

PI_NAMEs: DUBOIS, NICOLE  (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, BRYANNA NICOLE

PROJECT_TERMS: Actinin;Actins;Adult;alpha Actinin;Biochemical;Biological Process;Biology;biophysical properties;Body Composition;candidate identification;Cardiac;Cardiac Myocytes;cardiogenesis;Cardiomyopathies;Cell membrane;Cellular Structures;Clustered Regularly Interspaced Short Palindromic Repeats;comparative;Complex;Congenital Heart Defects;Contracts;CRISPR interference;Data;Development;Disease;Embryo;Fluorescence Recovery After Photobleaching;Gene Expression;Genetic;Heart;heart function;Homeostasis;human pluripotent stem cell;Image;Individual;Knowledge;Lead;Light;Liquid substance;Location;Mass Spectrum Analysis;Membrane;Mesoderm;Messenger RNA;Microfilaments;Microscopy;Molecular;Monitor;mouse model;Mus;novel;Organelles;Organism;Outcome;Phase;Physical condensation;pluripotent stem cell differentiation;Process;Property;Proteins;Research;Role;Sarcomeres;screening;Signal Transduction;Small Interfering RNA;small molecule;stoichiometry;Structure;Subcellular structure;superresolution microscopy;Tertiary Protein Structure;Transcript;Transmission Electron Microscopy;Tubulin;ultra high resolution

PROJECT_TITLE: Mechanisms of de novo cardiac sarcomere assembly

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDD-Q (81)]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE:  There is an urgent need for the establishment of new immunomodulatory approaches to reverse immune suppression in glioblastoma. The focus of this work is to validate a new therapeutic strategy for glioblastoma based on small molecule-based inhibition of a key immunosuppressive pathway. Optimized inhibitors from this work may synergize with immune checkpoint inhibitors to effectively promote tumor regression for glioblastoma patients.

PI_NAMEs: GABR, MOUSTAFA  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: absorption;Adjuvant;aggressive therapy;Angiogenesis Inhibitors;Animals;Astrocytoma;Attenuated;bevacizumab;Binding;Biological Assay;Blood - brain barrier anatomy;blood-brain barrier crossing;blood-brain barrier permeabilization;Brain Neoplasms;Cells;chemotherapy;CHI3L1 gene;Chitinase;clinical translation;Clinical Trials;Combined Modality Therapy;design;Development;Diffuse;Digit structure;Docking;drug candidate;drug discovery;Drug Kinetics;efficacy evaluation;Energy Transfer;Evaluation;Excretory function;Failure;Fluorescence;Free Energy;Galectin 3;Glioblastoma;Glioma;Glycoproteins;Goals;high throughput screening;Hybrids;Immune;Immune checkpoint inhibitor;immune modulating agents;Immune system;Immunomodulators;immunopharmacology;immunoregulation;Immunosuppression;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;Infiltration;inhibitor;Investigation;Lead;lead optimization;Libraries;Ligand Binding;Malignant - descriptor;Mediator;Metabolism;migration;Modeling;Molecular;mouse model;Mus;Myeloid-derived suppressor cells;nanomolar;Natural Killer Cells;Nature;Neoadjuvant Therapy;neoplastic cell;new combination therapies;novel therapeutic intervention;Operative Surgical Procedures;Outcome;overexpression;Pathway interactions;Patients;Peptides;phase III trial;Phenotype;Population;Positioning Attribute;Pre-Clinical Model;preclinical evaluation;Primary Brain Neoplasms;Prognosis;Proteins;Protocols documentation;Radiation therapy;randomized trial;Reporting;Research;resistance mechanism;Route;screening;small molecule;small molecule inhibitor;small molecule libraries;success;Supportive care;Surface Plasmon Resonance;synergism;T-Lymphocyte;Testing;Therapeutic;therapeutic evaluation;Time;tumor;Tumor Immunity;tumor microenvironment;tumor progression;Tumor Promotion;Tumor-associated macrophages;Tumor-Infiltrating Lymphocytes;Work

PROJECT_TITLE: CHI3L1-targeted small molecules for glioblastoma

STUDY_SECTION: DMPC

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology C Study Section[DMPC]