ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alcoholism, Alcohol Use and Health;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Pediatric;Physical Activity;Substance Misuse;Underage Drinking

ORG_CITY: BINGHAMTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: STATE UNIVERSITY OF NY,BINGHAMTON

PHR: C7/8 UO1: Lisa Savage & Ryan Vetreno Recovery of Adolescent Alcohol Disruption of Basal Forebrain-Cortical Projection Circuits Project Narrative Heavy adolescent alcohol consumption is associated with frontal cortical pathology and impaired decision making. Loss of cholinergic neurons and function is observed after adolescent alcohol exposure. This project rescues cholinergic neurons to restore cognitive function in an animal model of adolescent alcohol exposure.

PI_NAMEs: SAVAGE, LISA M (contact)

PROGRAM_OFFICER_NAME: BALAKATHIRESAN, NAGARAJA SETHURAMAN

PROJECT_TERMS: Acetylcholine;Adolescence;Adolescent;adolescent alcohol exposure;adolescent binge drinking;Adult;aged;Alcohol consumption;alcohol exposure;Alcohols;Alzheimer's Disease;Animal Model;Anxiety;ATAC-seq;Attention;basal forebrain;basal forebrain cholinergic neurons;Behavior;Behavioral;Brain;Brain Injuries;Cells;cholinergic;Cholinergic Fibers;cholinergic neuron;Chromatin;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Cognition;Cognitive;cognitive function;Complement;Complex;connectome;Coupled;Data;Decision Making;density;designer receptors exclusively activated by designer drugs;Development;discounting;Dissection;drinking;early adolescence;effective therapy;EP300 gene;Epigenetic Process;epigenetic regulation;epigenetic silencing;Ethanol;Exercise;Exercise Therapy;flexibility;frontal lobe;Functional disorder;gene therapy;Genes;Genetic;Goals;Growth Factor Gene;human model;Impaired cognition;Impairment;innovation;knock-down;Maintenance;Maps;Medial;Mediating;Mediator;Modeling;Monkeys;Nerve Degeneration;Nerve Growth Factors;nerve supply;nestin protein;Neurodegenerative Disorders;neuroimaging;Neuroimmune;neuron loss;Neurons;neuroprotection;NGFR gene;NGFR Protein;Nucleus Basalis Magnocellularis;Pathologic;Pathology;Pattern;Phenotype;phenotypic biomarker;Prefrontal Cortex;Process;Prosencephalon;Rattus;Recovery;reinnervation;Research;restoration;Reversal Learning;Rodent Model;Role;Short-Term Memory;Signaling Molecule;Site;Source;Structure;Techniques;Testing;tool;underage drinking;Viral

PROJECT_TITLE: 7/8 NADIA U01 Recovery of Adolescent Alcohol Disruption of Basal Forebrain-Cortical Projection Circuits


ADMINISTERING_IC: NS

ARRA_FUNDED: N

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: Groton

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: VIRTUS THERAPEUTICS CORPORATION

ORG_STATE: CT

PHR: Administrative Supplement Request for NIH Grant 1R43NS127740-01A1 Principal Investigator (PI): Jessica Regan, PhD  Scientific Director  Virtus Therapeutics Corporation  93 Shennecossett Rd, Groton CT, 06340  Phone: (570) 903-5378  Email: jessicaregan.virtustherapeutics@gmail.com Grant Title: PANK Activators for the treatment of pantothenate kinase-associated neurodegeneration Grant Number: 1R43NS127740 Funding Opportunity Announcement (FOA) Number: PA-21-345 Budget Period: 09/15/2023 -08/31/2024 Project Period: 09/15/2023 -08/31/2025 Amount of Supplement Request: $99,000 1. Introduction This request is for an administrative supplement to NIH grant 1R43NS127740, titled “PANK Activators for the treatment of pantothenate kinase-associated neurodegeneration” due to unforeseen increases in animal costs that were not anticipated at the time of the original budget submission. The supplement will ensure the continuation and successful completion of the proposed research. 2. Justification Most of the funds from the initial reward designated for animals have been used to breed, maintain, and perform drug treatments using the whole-body pank2-/- mouse model of PKAN. There is no observable phenotype associated with the whole-body pank2-/- mouse model, therefore, we initiated breeding of SynCrepank1fl/flpank2fl/fl mice, which display symptoms associated with PKAN including weight loss, locomotor disfunction, and early death. Whole-body pank2-/- mouse model of PKAN.  • We received pank2-/+ heterozygous mice from the Hayflick lab on 01/26/2022 and began breeding them  to obtain pank2-/- homozygous progeny, at a rate of 25%. A total of 191 homozygous pank2-/- animals  were obtained throughout one year of breeding.  • We did not see upregulation or downregulation of genes as previously reported for this model1. The  breeding pairs we received were at the end of their backcross cycle, therefore it was possible that the  RTqPCR results were due to the late cycle, therefore backcrosses were recommended. Heterozygous  pank2+/- mice were bred with C57B6 mice across three generations. After the third generation, three  males were selected, and their sperm cryopreserved.  • Homozygous pank2-/- mice were treated with vehicle, VTAC-1 and VTAC-2, as well as PZ2891 as a  control, for 14 days. Brains were removed and dissected into four parts: the Globus Pallidus (GP), the  Substantia Nigra (SN), olfactory bulb, and cerebellum. Total  RNA from collected tissues were extracted using phenol/chloroform method with QIAzol  and used in qRT-PCR to determine transcript levels of genes relating to CoA biosynthesis. Additionally, CoA levels in each region will be quantified to confirm activation of CoA biosynthesis. Analysis of gene transcript and CoA levels is ongoing. SynCrepank1fl/flpank2fl/fl mouse model of PKAN  • As stated in the alternative approach section in aim 3 of the parent grant, an additional mouse model of  PKAN was originally reported by the team of Dr. Jackowski at St. Jude and has subsequently been used  by BridgeBio to validate efficacy of PKAN therapeutic, BBP-671. This model has been used to study  PKAN as the mice exhibit symptoms similar to individuals diagnosed with PKAN including weight loss,  locomotor impairment and early death2. • We received pank1fl/fl sperm and pank2-/- embryos and began mouse breeding in March 2023. Initial  genotyping revealed three pank2 genotypes and one pank1 genotype: pank2fl/+, pank2fl/fl, and pank2fl/-,  and pank1fl/+. Pank1fl/+ mice were bred with mice expressing each of the three pank2 genotypes to  generate 52 pank1fl/+/pank2fl/+ mice and one pank1fl/+/pank2fl/fl mouse. • SynCre hemizygous mice were obtained from Jackson labs and were bred with mice expressing  genotypes Pank1fl/fl/Pank2fl/+ and Pank1fl/+/Pank2fl/fl to generate Pank1fl/fl/Pank2fl/+SynCre+ and  Pank1fl/+/Pank2fl/flSynCre+. These mice will be bred with Pank1fl/fl/Pank2fl/fl to generate the target mice  expressing SynCrepank1fl/flpank2fl/+ and SynCrepank1fl/+pank2fl/fl genotypes. After each round of breeding,  mice will be genotyped from nail clippings to select for SynCrepank1fl/flpank2fl/fl mice. As  SynCrepank1fl/flpank2fl/fl mice are generated, treatments will begin to maintain consistency of mouse age  between treatments. Sperm from key intermediate stages will be frozen and stored for future breeding.  We expect to have SynCrepank1fl/flpank2fl/fl mice ready for the proposed studies by the end of 2024. See  diagram for breeding details. • Groups of mice consisting of 5 females and 5 males will be housed under 12h light cycles with free  access to chow and water and dosed with 10 mg/kg (of the front-runner VTAC compounds and PZ-2891  and BBP-671 as controls) via oral gavage once daily for 14 days and monitored daily for their weight  and activity. Following treatment, mice symptoms will be monitored including changes in weight and  motor function. The brains of mice which show symptomatic improvement will be removed and dissected  in regions containing the Globus Pallidus (GP), Substantia Nigra (SN), olfactory bulb, and cerebellum.  Total RNA will be collected from tissues and extracted using the phenol/chloroform method with QIAzol  and used in qRT-PCR analysis to quantify mRNA levels of the CoA biosynthetic genes and key markers  of iron and dopamine dyshomeostasis. CoA levels in the brain will be measured by LC/MS-MS and  intracellular iron concentrations will be quantified by ICPMS (Inductively-Couple Plasma Mass Spectroscopy). • Success will be determined by the ability of the VTACs to improve symptoms associated with PKAN,  extend survival, restore CoA levels, and correct of iron and dopamine dyshomeostasis markers. 3. Description of Costs  • Strain reanimation (IVF): $1100/service  • Strain reanimation (embryos): $750/derivation  • Housing cost per diem: $1.27 per cage  • Cryopreservation: $750 per sperm  • Tissue collection: $72/hour  • Mouse genotyping: $10 per mouse 4. Impact on Research The increased costs have put the project at risk of not being able to achieve its specific aims. Without this supplement, we will not be able to continue breeding SynCrepank1fl/flpank2fl/fl mice for treatment with VTACs. The requested funds are essential for maintaining the integrity and scope of the research as originally proposed. 5. Budget Item Cost Housing and Care $59,000 Tissue collection/data analysis $40,000 Total Supplement Request $99,000 6. Timeline The additional funds are needed immediately to cover the increased costs. Upon approval, we anticipate no delays in the project timeline and expect to complete the project as originally scheduled by 08/31/2025. 7. PI Assurance I assure that the requested supplemental funds will be used solely for the purpose of covering the costs associated with studies involving the use mouse models of PKAN conducted under the Sponsored Research Agreement with Dr. Ben Mamoun at Yale and performed at the Yale Animal Core Facility. No other aspects of the project will be altered. 8. Signatures Principal Investigator: Jessica Regan June 17, 2024 Authorized Institutional Official: Choukri Ben Mamoun Founder and Signing Official Choukri Ben Mamoun July 21, 2024 Summary of parent grant  • Aim 1: Characterize PTZ analogs for in vitro activity and selectivity  o Proposed  ▪ Nine VTACs have been characterized for modulation of human PANK3 activity. Here, we  will extend analysis to an additional 29 analogs to identify top compounds based on their  modulation of PANK activity. o Achieved  ▪ In addition to the original nine VTACs, five compounds were confirmed to specifically  activate human PANK3 using an ATPase assay with purified hPANK3 enzyme.  • Aim 2: Further examine the safety of the compounds and evaluate their in vitro cell biological  activity in PANK2-deficient cells. o Proposed  ▪ Extend analyses of hPANK3 activation and toxicity profile of the 14 VTACs and conduct  cell-based assays to identify those that restore biological activity in PANK2-deficient cells  and select ideal candidates for animal models. o Achieved  ▪ Further analyses are being conducted to examine the safety of the initial 9 VTACs as well  as the addition 5 compounds identified in Aim 1. The in vitro cytotoxicity of each of these  compounds is being tested on four human cell lines (HeLa, HepG2, HEK293, and  HCT116) and one primary cell line (HFF-BJ). So far, the initial 9 VTACs have been tested  in the four human cell lines at concentrations up to 100 µM and their toxicity was  compared to PZ-2891. The 9 VTACs tested had similar cytoxicity levels compared to PZ-  2891 in each of the four cell lines, with the majority of the 9 VTACs having IC50’s >100  µM. Cytotoxicity studies with the remaining 5 compounds in these four human cell lines,  as well as all 14 compounds in the primary cell line are ongoing.  ▪ Further evaluation of in vitro cell biological activity of the VTACs are being conducted to  select lead compounds for clinical development. Cell-based assays are ongoing to  identify those compounds which restore biological activity in PANK2-deficient cells.  Treatment of PANK+/+-CoA-Luc and PANK/--CoA-Luc cells with each of the 14 VTACs is  in progress. Cells will be cultured in plates and treated with different doses of the  activators ranging between 1 nM and 1μM or vehicle (media or DMSO) for 24h, with PZ-  2891 as a control. Analysis of relative mRNA levels of CoA biosynthetic genes and other  related genes was conducted in PKAN patient cell lines compared to healthy patient cell  lines as well as HFF wild-type and pank2 knock-out cell lines to identify genes whose  expression levels are altered by PANK2 deficiency. These studies demonstrated reduced  expression of Transferrin Receptor (TFRC) similar to that of PANK2 in PKAN patient cell  lines as well as pank2 knock-out cell lines. Based on these studies, qRTPCR will be  performed to determine if the 14 VTACs can restore expression of TFRC. MTT  colorimetric assay is used to measure cell metabolic activity in untreated and treated  PKAN and control cells following conversion of the tetrazolium dye MTT into its insoluble  formazan. The MTT assay has so far been completed with the initial 9 VTAC compounds. • Aim 3: Evaluate the in vivo efficacy of lead VTAC activators in mouse models of PKAN.  o Proposed  ▪ Initial PK and CNS exposure studies in mice have so far identified VTAC-1 and VTAC-2 as  leads for further evaluation in the mouse model of PKAN.  We will first evaluate these 2 compounds as well as new leads that meet rigorous criteria  for testing in animals for their in vivo pharmacokinetic and safety. Selected compounds  will then be evaluated for in vivo efficacy in pank2-/- mice by monitoring important PKAN  biological metrics including activation of the CoA metabolic pathway, iron homeostasis,  mitochondrial metabolism, and rescue of PKAN-like phenotypes.  o Achieved  ▪ Whole-body pank2-/- mouse model of PKAN were bred from pank2-/+ heterozygous mice  at a rate of 25%.  ▪ Groups of 5 females and 5 males were dosed with 0, 10, and 30 mg/kg of VTAC-1 and  VTAC-2, as well as PZ-2891 as a control. The brain of each mouse was removed and  dissected in regions containing the Globus Pallidus (GP), Substantia Nigra (SN), olfactory  bulb, and cerebellum. RNA from the collected tissues was extracted and qRT-PCR  performed to measure levels of key CoA biosynthetic genes. CoA levels in each brain  region will be quantified by LC/MS-MS.  ▪ Samples from untreated PKAN knock-out and wild-type male and female mice were sent  for LC-MS and metabolomics to quantify RNA transcript levels. RTqPCR analysis on  tissues has been completed, however, the expected upregulation or downregulation of  key genes as described by the Hayflick lab were not observed. Preliminary analyses  indicate a slight increase in CoA levels in the brain upon treatment with VTAC-2 in wild-  type mice compared to vehicle treatment. Further analysis of CoA levels is ongoing and  we expect results to be available by the end of 2024. (1) Jeong, S. Y.; Hogarth, P.; Placzek, A.; Gregory, A. M.; Fox, R.; Zhen, D.; Hamada, J.; van der Zwaag, M.; Lambrechts, R.; Jin, H.; et al. 4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN. EMBO Mol Med 2019, 11 (12), e10489. DOI: 10.15252/emmm.201910489. (2) Sharma, L. K.; Subramanian, C.; Yun, M. K.; Frank, M. W.; White, S. W.; Rock, C. O.; Lee, R. E.; Jackowski, S. A therapeutic approach to pantothenate kinase associated neurodegeneration. Nat Commun 2018, 9 (1), 4399. DOI: 10.1038/s41467-018-06703-2.

PI_NAMEs: REGAN, JESSICA  (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, FLOY ANNETTE

PROJECT_TERMS: 4'-phosphopantetheine;Administrative Supplement;Age;Agreement;Anabolism;analog;Animal Model;Animals;animation;associated symptom;ATP phosphohydrolase;Authorization documentation;Backcrossings;Biochemical;Biological;Biological Assay;Body Weight decreased;Brain;Brain region;Breeding;Budgets;Caring;Cell Line;Cells;Cerebellum;Cessation of life;Chemicals;Chloroform;Clinical;clinical development;Clip;Coenzyme A;Core Facility;cost;Cryopreservation;cytotoxicity;Data;Data Analyses;Defect;Derivation procedure;Development;Diagnosis;Dimethyl Sulfoxide;Disease;Disease Progression;Doctor of Philosophy;Dopamine;Dose;Down-Regulation;Drug Kinetics;Dyes;efficacy validation;Electronic Mail;Embryo;emerging adult;Ensure;Enzymes;Evaluation;Exhibits;Family;Female;Formazans;Freezing;Functional disorder;Funding;Funding Opportunities;Future;gene repression;Generations;Genes;Genotype;Globus Pallidus;Goals;Grant;HCT116 Cells;Hela Cells;HepG2;Heterozygote;Homeostasis;Hour;Housing;Human;Human Activities;Human Cell Line;Immobilization;Impairment;In Vitro;in vitro activity;in vivo;Individual;Institution;Iron;Knock-out;Lead;lead optimization;Libraries;Light;liquid chromatography mass spectrometry;male;Mass Spectrum Analysis;Measures;Messenger RNA;Metabolic;Metabolic Pathway;metabolomics;meter;Methods;Mitochondria;mitochondrial metabolism;Modeling;Monitor;Motor;mouse model;Mus;Mutate;Mutation;Nail plate;Neurodegenerative Disorders;olfactory bulb;Oral;Pantothenate kinase;Pantothenate kinase-associated neurodegeneration;parent grant;Patients;Pharmaceutical Chemistry;Pharmacotherapy;Phenols;Phenotype;Physiological;Plasma;Principal Investigator;Production;Property;Quantitative Reverse Transcriptase PCR;Recommendation;Reporting;Research;research clinical testing;Rewards;Risk;RNA;Safety;Saint Jude Children's Research Hospital;Sampling;Schedule;screening;Services;Solubility;sperm cell;sperm cryopreservation;Substantia nigra structure;success;symptom management;symptomatic improvement;Symptoms;Telephone;Testing;Tetrazolium;TFRC gene;Therapeutic;Therapeutic Index;Time;timeline;Tissue Banks;Tissues;Toxic effect;Transcript;United States National Institutes of Health;Up-Regulation;Water;Weight;Wild Type Mouse

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(11)-B]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Asthma;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Pediatric;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_DEPT: PEDIATRICS

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: NARRATIVE The overarching goal of this project is to improve care and reduce health disparities in care quality and outcomes for children with asthma. This timely, policy-driven project focuses on disadvantaged children covered by Medicaid, and addresses the lack of improvement in asthma-related childhood hospitalization rates and mortality in the past decade. The proposed research is designed to identify underlying causes of persistent disparities in childhood asthma and influence evidence-based change in healthcare and outcomes, using linked multi-source data and advanced analytic and simulation methods to achieve this goal.

PI_NAMEs: CHORNIY, ANNA  (contact)

PROGRAM_OFFICER_NAME: FREEMER, MICHELLE M

PROJECT_TERMS: 18 year old;academic preparation;Accounting;Address;Adolescent;Adult;advanced analytics;Affect;Algorithms;American;Architecture;Asthma;beneficiary;Biological;Black race;Caring;Characteristics;Child;Child Health;Childhood;Childhood Asthma;Chronic;Clinical;clinical care;Community Surveys;comorbidity;Complement;Contracts;cost;Data;Data Analyses;Data Analytics;Data Set;Death Rate;design;Development;Diagnosis;disability;Disadvantaged;Disparate;Disparity;disparity reduction;Economic Burden;economic evaluation;Economics;Education;Emergency department visit;ethnic minority;Ethnic Origin;evidence base;experience;experimental analysis;experimental study;Family;Family Characteristics;Fee-for-Service Plans;Funding;Future;Geography;Goals;Health;health care disparity;health difference;health economics;Health Insurance;Health Personnel;Healthcare;Hospitalization;hospitalization rates;Impairment;implementation strategy;improved;Income;Individual;Inequity;innovation;Insurance;Insurance Coverage;insurance plan;Justice;Knowledge;Leadership;Link;Low income;lower income families;Managed Care;Managed Care Programs;Measures;Medicaid;Medicare;Mentors;Methodology;Methods;minority children;Modeling;mortality;multidisciplinary;National Heart, Lung, and Blood Institute;Natural experiment;Neighborhoods;Not Hispanic or Latino;novel;Outcome;outcome disparities;Patient-Focused Outcomes;Patients;Persons;Policies;Population;population health;premature;preventable death;Privatization;programs;provider factors;provider networks;Quality of Care;Quality of life;Race;racial minority;Randomized;Records;Reduce health disparities;Research;Research Design;Research Personnel;Research Priority;Risk Factors;Role;Secure;Services;Shapes;simulation;skills;Social Environment;social health determinants;Societies;sociodemographics;socioeconomics;Source;South Carolina;Specific qualifier value;Time;Training;Uninsured;Variant;Vital Statistics;Work

PROJECT_TITLE: Outcomes for Children with Asthma on Medicaid: Elucidating Key Determinants at the Policy, Plan, Neighborhood, and Person Levels to Address Disparities

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(JA)]


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

NIH_SPENDING_CATS: Asthma;Biotechnology;Chronic Obstructive Pulmonary Disease;Clinical Research;Genetics;Lung

ORG_CITY: SAINT LOUIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative/Public Health Relevance Chronic Obstructive Pulmonary Disease is a major cause of morbidity worldwide and the 3rd leading cause of death in the United States. There are no cures for this disease and the standard forms of treatment often do not provide adequate relief, as much of the morbidity and mortality is due to mucus obstruction of the airways. There are currently no specific and effective therapies available for excess mucus production. The proposed work aims to identify new ways to treat this disorder by investigating the source of inflammation and mucus overproduction in the airways, thereby addressing a previously unmet need for treatment of a major public health problem.

PI_NAMEs: ALEXANDER-BRETT, JENNIFER  (contact)

PROGRAM_OFFICER_NAME: LIU, QIAN

PROJECT_TERMS: Acute;Address;Affinity;Airway Disease;airway epithelium;airway obstruction;Allergens;Alternaria;Animal Model;Asthma;asthma exacerbation;Automobile Driving;Binding;Biological Assay;Biology;Bronchoalveolar Lavage;Bypass;Cause of Death;Cell model;Cell Nucleus;Cell secretion;Cells;Chronic;Chronic Bronchitis;Chronic Disease;Chronic Obstructive Pulmonary Disease;chronic respiratory disease;Clinical Research;Complex;Coupled;cytokine;Cytoplasm;Data;Development;Diagnosis;Disease;disease model;disease phenotype;effective therapy;Endosomes;Enzyme-Linked Immunosorbent Assay;Epithelial Cells;epithelial stem cell;Epithelium;Exhibits;Exons;exosome;Foundations;genome wide association study;Heat-Shock Proteins 70;Human;IL8 gene;In Vitro;in vivo;Inflammation;insight;Interferometry;knock-down;Knowledge;Length;Liquid substance;live cell imaging;Lower respiratory tract structure;Mass Spectrum Analysis;Measures;Mediating;Mediator;Messenger RNA;Metaplasia;mimetics;Molecular;Molecular Chaperones;Morbidity - disease rate;mortality;mouse model;Mucous body substance;Mucous Membrane;Mus;mutant;Necrosis;novel;novel strategies;Nuclear;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Peptide Signal Sequences;Phosphorylation;Play;Post-Translational Protein Processing;Process;Production;protein expression;Protein Isoforms;Protein Secretion;Proteins;Proteomics;Public Health;public health relevance;Pulmonary Emphysema;Reagent;receptor;Receptor Activation;receptor binding;Receptor Signaling;recruit;Research;Respiratory Tract Diseases;RNA Splicing;Role;Signal Transduction;Smoke;Source;Specimen;Sphingomyelinase;Structure;Structure of parenchyma of lung;System;Testing;Therapeutic Intervention;trafficking;translational study;United States;Validation;Viral;Virus;Western Blotting;Work;X-Ray Crystallography

PROJECT_TITLE: Non-Classical Cytokine Secretion in Chronic Airway Disease

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Services;Opioid Misuse and Addiction;Opioids;Pediatric;Prevention;Primary Health Care;Substance Misuse;Telehealth

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PSYCHIATRY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Since 2020, the overdose crisis has expanded most rapidly among younger populations, largely due to illicit substances containing lethal amounts of fentanyl, but access to effective treatment for adolescents with opioid use disorder (OUD) and other substance use disorders (SUD) is severely limited by gaps in the SUD specialist workforce. Primary care is a promising setting for expanding SUD/OUD services; however, primary care providers often lack the training, resources, and supports to deliver SUD/OUD services confidently and effectively. This study will leverage a large-scale rollout of integrated behavioral healthcare in a statewide health system to investigate the implementation and effectiveness of a multifaceted intervention (brief interventionists embedded in primary care, case management, decision support tools in the electronic health record, and stigma reduction interventions) to increase delivery of adolescent SUD/OUD services and, ultimately, to prevent overdose deaths.

PI_NAMEs: AALSMA, MATTHEW ;ADAMS, ZACHARY WILLIAM;HULVERSHORN, LESLIE A. (contact)

PROGRAM_OFFICER_NAME: LYNCH, SEAN EDWARD WINTERS

PROJECT_TERMS: addiction;Address;Adolescent;adolescent substance use;Adult;Age;Attitude;behavioral health;brief intervention;Buprenorphine;Caring;Case Management;Childhood;Clinical Management;Cluster randomized trial;Communities;Consultations;Coupled;Development;Diagnosis;Disease;Disparity;dual diagnosis;effective therapy;Effectiveness;Electronic Health Record;Electronics;Ensure;Etiology;Evidence based treatment;experience;Face;Feeling;Fentanyl;fentanyl contamination;Funding;Health;Health Personnel;Health system;Healthcare;Hybrids;implementation evaluation;implementation outcomes;implementation science;implementation/effectiveness;improved;Indiana;Infrastructure;innovation;integrated care;Intervention;Mental disorders;Methamphetamine;Modeling;multi-component intervention;novel;opioid use;opioid use disorder;Outcome;Outpatients;Overdose;overdose death;overdose risk;Parents;Patients;person centered;Persons;Pharmacologic Substance;Pharmacology;Play;Population;prevent;Primary Care;primary care practice;primary care provider;primary care setting;Procedures;Process;programs;Provider;provider behavior;provider to provider;Qualifying;Randomized;Research;Research Design;Resources;response;Role;Scientist;screening;service delivery;Services;social stigma;Specialist;Stigmatization;substance use;Substance Use Disorder;support tools;Surveys;System;telehealth;Testing;Time;Training;treatment program;treatment services;uptake;Well Child Visits;willingness;Work;Youth

PROJECT_TITLE: Workforce and System Change to Treat Adolescent Opioid Use Disorder within Integrated Pediatric Primary Care


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Nutrition;Obesity;Prevention;Telehealth

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: The Health, Aging and Later-Life Outcomes Planning Grant (HALLO-P) supports activities necessary for planning of a 5-year study to investigate whether decreasing energy intake or changing the pattern of eating throughout the day can improve the health and well-being of older adults.

PI_NAMEs: KRITCHEVSKY, STEPHEN B. (contact);MILLER, MICHAEL E.;NICKLAS, BARBARA J;REJESKI, WALTER JOHN

PROGRAM_OFFICER_NAME: NELLISSERY, MAGGIE JACOB

PROJECT_TERMS: Adherence;Adult;Adverse event;Age;Aging;aging biomarker;American;attentional control;Attitude;Award;behavior change;Behavior Therapy;Biological Markers;Biometry;Body Weight decreased;bone;bone health;Caloric Restriction;Capsicum;Clinical;Clinical Trials;clinically relevant;Companions;Complex;Consent Forms;Continuous Glucose Monitor;Control Groups;Data;Data Analyses;data cleaning;data management;Data Set;Databases;design;Devices;Dietary Intervention;disability;disability risk;Disease;disorder risk;Documentation;Dose;doubly-labeled water;Eating;Energy Intake;Enrollment;Epidemiology;Event;Exclusion Criteria;Focus Groups;follow-up;functional decline;Funding;Funding Mechanisms;Geroscience;Goals;Grant;Health;Health Benefit;Hour;improved;Individual;innovation;Intervention;intervention delivery;intervention refinement;Intervention Trial;late life;Literature;Maintenance;Manuals;Measures;mHealth;Minority;Modeling;multiple chronic conditions;muscle metabolism;Muscular Atrophy;Obesity;obesity treatment;older adult;Older Population;operation;Outcome;Participant;Pattern;Personal Satisfaction;Persons;Phase;Physiological;Pilot Projects;pilot trial;Preparation;Process;Protocols documentation;Publications;Quality Control;Randomized;Randomized Controlled Clinical Trials;randomized, clinical trials;recruit;Regimen;remote delivery;Reporting;repository;Research Personnel;Resources;response;safety assessment;Sampling;Site;Structure;System;Time;Time-restricted feeding;tool;Translating;trial comparing;Videoconferencing;Woman

PROJECT_TITLE: Health Aging & Later-Life Outcomes - pilot (HALLO-P)


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Arthritis;Osteoarthritis;Physical Injury - Accidents and Adverse Effects

ORG_DEPT: ORTHOPEDICS

PHR: Degenerative and post-traumatic osteoarthritis are human diseases with high impact on US public health, with increasing economic relevance due to a non-linear increase in prevalence. Here, we propose to extend our recent discovery of PIEZO mechanically-sensitive ion channels’ role in mechanically-induced injury of chondrocytes, the cellular element of cartilage, by addressing the questions how – mechanistically – PIEZO channels function in chondrocytes, how they function in inflammatory conditions that mimic osteoarthritis, how they function in live animals, and how their function can be attenuated toward a disease-modifying therapy.

PI_NAMEs: GUILAK, FARSHID  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Address;Affect;Age;Age Years;Aging;anakinra;Animals;antagonist;Anti-Inflammatory Agents;arthropathies;articular cartilage;ATF2 gene;Attenuated;attenuation;Binding;Biochemical;biological adaptation to stress;Body Weight;Cartilage;Cartilage injury;Cell model;Cells;Chondrocytes;chondroprotection;Complex;Coxibs;cytokine;Degenerative polyarthritis;Dependence;Development;disability;Disease;Dynamin;economic impact;Economics;Electrophysiology (science);Elements;Environment;experimental study;Exposure to;Family suidae;frailty;Friction;Gene Expression;Gene Expression Regulation;Genetic Transcription;Grant;Health;HNF4A gene;Human;human disease;human old age (65+);Hypersensitivity;IL1R1 gene;in vivo;Inflammation;Inflammatory;inhibitor;Injury;insight;Interferons;Interleukin-1 alpha;Ion Channel;joint injury;joint loading;Joints;Life;Link;loss of function;mechanical force;mechanical properties;mechanical signal;Mechanical Stress;Mechanics;mechanotransduction;Mediating;meloxicam;Membrane;Metabolic;Methods;Modeling;Morphology;Mus;Non-Steroidal Anti-Inflammatory Agents;Obesity;osteochondral tissue;Pain;Pathogenesis;Pathologic;Pathway interactions;Pharmaceutical Preparations;Phenotype;Physiological;Piezo 1 ion channel;Piezo 2 ion channel;Piezo ion channels;Population;Prevalence;Process;promoter;Public Health;radiological imaging;response;response to injury;Role;Signal Transduction;skeletal;Social isolation;Societies;socioeconomics;Surface;synergism;Synovial joint;Testing;Therapeutic;trafficking;transcription factor;Trauma;Traumatic Arthropathy;United States;voltage

PROJECT_TITLE: Deconstructing Cartilage Mechanotransduction by Piezo Channels

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


ADMINISTERING_IC: FD

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: RICHMOND

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Generic versions of commercial orally inhaled medications are expected to reduce drug costs and thereby improve usage and control of respiratory diseases; however, development and regulatory review of these drug products are complex due to a lack of knowledge about regional lung doses leading to very few generic inhaled medications reaching the US market. The objective of this study is to develop and validate new open-source computational fluid dynamics (CFD) methods for a solution-based metered dose inhaler (MDI) product that can accurately predict regional drug deposition throughout the airways, and then implement the model to establish in-vitro-in-vivo-correlations (IVIVCs) between US Food and Drug Administration recommended in vitro test metrics and in vivo regional lung deposition. Both the new computational model and developed correlations are intended to predict regional lung doses of inhaled medications and thereby assist with the development and regulatory approval of more generic orally inhaled medications.

PI_NAMEs: LONGEST, P. WORTH  (contact)

PROGRAM_OFFICER_NAME: WALENGA, ROSS

PROJECT_TITLE: Computational Fluid Dynamics (CFD) Models to Aid the Development of Generic Metered Dose Inhalers


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Mental Health;Neurosciences;Pain Research;Pediatric;Prevention;Rare Diseases;Sickle Cell Disease;Social Determinants of Health

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Chronic pain significantly diminishes all aspects of quality of life among children and adolescents with sickle cell disease (SCD), yet there are limited effective treatments available to date. This research will adapt and tailor an existing evidence-based innovative mind-body, cognitive-behavioral, and neuromuscular movement intervention to meet the unique needs of adolescents with chronic sickle cell pain and test the new intervention (termed I- STRONG for SCD) in a multi-center randomized clinical trial. The long-term goal of this research is to reduce functional impairment, pain, and common psychological comorbidities such as depression and anxiety, among youth with chronic pain in SCD to mitigate disparities in pain and health outcomes.

PI_NAMEs: SIL, SOUMITRI  (contact)

PROGRAM_OFFICER_NAME: CHIDEYA-CHIHOTA, SEKAI RUTENDO

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Adolescence;Adolescent;Adult;Adverse effects;Affect;African American population;Aftercare;Age;Anxiety;arm;Behavioral;Biological Factors;biopsychosocial factor;Black American;Breathing;Caring;Child;Childhood;Chronic;Chronic Disease;chronic pain;chronic pain management;Clinical;clinical implementation;Clinical Practice Guideline;Clinical Trials;Cognitive;Communities;community engagement;comorbid depression;comorbidity;Complex;depressive symptoms;design;disability;disparity reduction;Educational Intervention;effective therapy;Effectiveness;effectiveness evaluation;Enrollment;Ensure;evidence base;Exclusion;experience;Family;family management;Feedback;Fibromyalgia;follow-up;Fright;Functional impairment;Goals;Guided imagery;Health;health disparity;health related quality of life;Health Services Accessibility;improved;improved outcome;Individual;innovation;Integrative Therapy;interdisciplinary treatment approach;Intervention;iterative design;juvenile onset fibromyalgia;Life;Lived experience;Measures;Mental Depression;Methods;Mind-Body Intervention;mind/body;Minority Groups;Modeling;Movement;multi-component intervention;Multicenter Trials;Muscle relaxation phase;neuromuscular;Nonpharmacologic Therapy;optimal treatments;Outcome;Pain;pain catastrophizing;Pain intensity;Pain interference;Pain management;Parents;Participant;patient engagement;patient retention;Patients;Pharmacological Treatment;Phase;Physical activity;preference;primary endpoint;primary outcome;programs;psychologic;Psychological Factors;Quality of life;racial disparity;Randomized;randomized, clinical trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Research;Respiratory Diaphragm;Sampling;satisfaction;secondary outcome;Sickle Cell;Sickle Cell Anemia;Site;social factors;standard care;Teenagers;telehealth;Telemedicine;Testing;therapy design;Time;Training;Training Programs;Waiting Lists;Work;Youth

PROJECT_TITLE: Integrative Training Program for Pediatric Sickle Cell Pain


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric

ORG_NAME: TRANSCENDENT INTERNATIONAL, LLC

PHR: PROJECT NARRATIVE As highlighted in the NICHD strategic plan, technology use by children is a priority area for research as it impacts a child’s neurocognitive, behavioral, linguistic, and social-emotional outcomes. Despite ongoing efforts by medical associations and advocacy groups to provide up-to-date guidance, parents and educators continue to find it challenging to moderate children’s digital media consumption in a healthy way. This project addresses the growing need to make recommendations about healthy technology use actionable for families of diverse backgrounds through bilingual storytelling, interactive games, and co-play in order to translate guidance into everyday routines.

PI_NAMEs: D'ANTILIO, YUAN  (contact)

PROGRAM_OFFICER_NAME: PARSAFAR, PARISA

PROJECT_TERMS: 6 year old;Academy;Acute;Address;Adopted;Advocacy;Advocate;Age;age group;American;Area;Articulation;Attitude;Awareness;Behavior;Behavioral;bilingualism;Books;Caregiver support;Caregivers;catalyst;Child;Child Rearing;Code;Communication;Computer software;Consumption;COVID-19 pandemic;Data;Decision Making;design;Development;Devices;digital;digital media;digital technology;E-learning;Education;Educational process of instructing;Effectiveness;electronic book;Emotional;empowerment;Ensure;Environment;Evaluation;evidence base;Face;Family;Feedback;Flowers;Fostering;Friends;Generations;Goals;Habits;health care disparity;Health education;health equity;Home environment;Household;Hybrids;improved;Informatics;information gathering;interest;Intervention;Interview;Joints;Knowledge;Language;Language Development;Learning;Libraries;Linguistics;Literature;Measures;media use;Medical;meetings;Methodology;Minority;Modeling;National Institute of Child Health and Human Development;Neurocognitive;Outcome;Pamphlets;Paper;Parent-Child Relations;Parents;Participant;Pediatrics;Phase;Play;Positioning Attribute;Process;Proliferating;prototype;Provider;Questionnaires;randomized, controlled study;Recommendation;Research;Research Priority;Resources;Respondent;Role;Scheme;Series;skills;Small Business Innovation Research Grant;social;Social Interaction;Strategic Planning;Stream;Surveys;Technology;Testing;Translating;Translational Research;tv watching;underserved community;usability;verbal;Video Recording;virtual;virtual world;web platform

PROJECT_TITLE: A Translational Research Approach to Healthy Technology Usage in Language-Minority Families with Young Children


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Genetics;Health Services;Hepatitis;Liver Disease;Organ Transplantation;Prevention;Substance Misuse;Transplantation

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Project Narrative Alcohol-associated liver disease represents a growing public health burden, particularly among younger age groups, women, and ethnic minorities, and is now the leading cause of liver transplantation in the United States. This project will identify predictors of outcome and improve prognostication in severely ill patients with alcohol- associated liver disease. Identifying reliable non-invasive markers that characterize the distinct phenotypes of alcohol-associated liver disease will be crucial to advance our understanding of this liver disease, target interventions, and appropriately allocate resources including liver transplantation.

PI_NAMEs: KWONG, ALLISON  (contact)

PROGRAM_OFFICER_NAME: GAO, PETER

PROJECT_TERMS: Abstinence;Academic Medical Centers;Acute;advanced disease;age group;alcohol abstinence;Alcohol consumption;Alcohol Phenotype;alcohol research;alcohol use disorder;Alcoholic Hepatitis;Alcoholic Liver Diseases;Ambulatory Care Facilities;Apoptotic;Ascites;Award;Bacterial DNA;Bilirubin;biobank;Biological;Biological Markers;career;career development;Cessation of life;Characteristics;chemokine;Classification;Clinical;clinical epidemiology;Clinical Investigator;Clinical Research;clinically relevant;cohort;Communication;Communities;Complex;cost;Creatinine;Cytokeratin-18 Staining Method;cytokine;Data;Data Analyses;Dedications;demographics;Development Plans;disease heterogeneity;disease phenotype;Disease Progression;disease registry;ethnic minority;Etiology;experience;Feces;fibrogenesis;Fibrosis;follow-up;Foundations;frailty;Future;Genetic Risk;genetic variant;Hemorrhage;Hepatic;Hepatitis;hepatocyte injury;high risk;Hospitalization;Hospitals;Image;Immunoassay;improved;Inflammation;Inflammatory;Institution;Intervention;Laboratories;lipidome;Lipopolysaccharides;Liver;Liver diseases;liver transplantation;Machine Learning;Measures;Mentorship;microbiome;MicroRNAs;Morbidity - disease rate;mortality;mortality risk;Multicenter Studies;multidisciplinary;Natural History;nutrition;Outcome;outcome prediction;Outcomes Research;Pathway interactions;Patient Care;Patient-Focused Outcomes;Patients;Pattern;pharmacologic;Phenotype;preclinical study;Principal Investigator;Procedures;Process;prognostication;programs;prospective;Psychosocial Influences;Public Health;radiological imaging;Recovery;recruit;Registries;Relaxation;Research;research and development;Research Personnel;Resource Allocation;Resources;Risk;risk prediction model;risk variant;sarcopenia;Serum;Severity of illness;Signal Transduction;skills;sobriety;sociodemographic factors;Subgroup;Susceptibility Gene;Techniques;Technology;Testing;Time;Training;transcriptome;Translating;translational study;Transplant Recipients;Transplantation;United States;Universities;urinary;Visit;Woman

PROJECT_TITLE: Defining Phenotypes of Alcohol-Associated Liver Disease with Acute Hepatic Decompensation

STUDY_SECTION: AA

STUDY_SECTION_NAME: Biomedical Research Study Section[AA-1]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Clinical Research;Dental, Oral, and Craniofacial Disease;Multiple Sclerosis;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative 7T MRI image quality is degraded by inhomogeneities in the static B0 and transmit B1+ fields, which reduce its overall diagnostic value and slows its translation to clinics. The B0 and B1+ problems have so far been approached independently, thus yielding two separate hardware solutions, namely multi-coil (MC) shim arrays for B0 shimming and parallel transmission (pTx) for flip-angle control, that are expensive and difficult to integrate and operate. We propose a new class of excitation pulses that leverage the degrees-of-freedom of MC shim arrays to homogenize the flip-angle distribution at 7T, thus yielding an integrated solution for both B0 and flip-angle shimming that is cheaper and bypasses the complex safety management of pTx, and may therefore be more readily deployed in clinics.

PI_NAMEs: GUERIN, BASTIEN  (contact);STOCKMANN, JASON P

PROGRAM_OFFICER_NAME: WANG, SHUMIN

PROJECT_TERMS: 3D Print;absorption;Administrative Supplement;Adult;Affect;Air;Anatomy;Biomedical Engineering;bone;Brain;Brain Neoplasms;Brain Stem;brain tissue;Bypass;Cell Nucleus;Cerebellum;Cerebrospinal Fluid;Clinic;Clinical;clinical translation;Complex;Cortical Dysplasia;cost;Data;design;Detection;Development Plans;diagnostic value;Diffusion;Diffusion Magnetic Resonance Imaging;Electromagnetics;External auditory canal;Family;Freedom;Gel;Geometry;Goals;gray matter;Head;Head and neck structure;Heterogeneity;human subject;Image;improved;Individual;individual variation;innovation;iterative design;Magnetic Resonance Imaging;Measurement;Measures;method development;Methods;Modeling;Multiple Sclerosis Lesions;multiple sclerosis patient;Muscle;Neck;Neurologic;Noise;open source;Oral cavity;Patients;Performance;Physiologic pulse;Play;Preparation;Procedures;Process;programs;Property;prototype;radio frequency;Reagent;Recipe;Relaxation;Research;research and development;Resolution;Safety Management;Signal Transduction;simulation;Sinus;Slice;Source;Spatial Distribution;Spinal Cord;Surface;System;Technology;Temporal Lobe Epilepsy;Testing;Tissues;Trachea;Translating;translational barrier;Translations;transmission process;Vertebral column;virtual;white matter;Work

PROJECT_TITLE: Head and neck anthropomorphic phantoms for MRI methods development at low and high fields


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative The goal of this project is to reveal the molecular mechanisms that enable synapses to rapidly modulate and sustain synaptic transmission for the proper encoding of auditory information. Inability to do so underpins problems with speech perception and sound localization in the aging population, auditory processing disorder and contributes to central auditory deficits in neurological disorders. Given these problems as a well as the pathological consequences of aberrant SV release, we envision that our findings will provide fundamental insights into how information is encoded by the nervous system and facilitate the development of treatments for a wide range of neurological and neuropsychiatric disorders.

PI_NAMEs: YOUNG, SAMUEL MATTHEW (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: Actins;Action Potentials;Affect;aging population;Animal Vocalization;Auditory;Auditory Perceptual Disorders;auditory processing;Auditory system;autism spectrum disorder;Automobile Driving;Axon;Behavioral;Binaural;Brain;Brain Diseases;Brain Stem;Cell Nucleus;Cells;Central Auditory Processing Disorder;Cochlear nucleus;Communication;conditional knockout;Cytoskeleton;Data;Defect;Electron Microscopy;Evoked Potentials;Frequencies;Glutamates;Goals;gutless adenoviral vector;Hearing;Hearing problem;Human;in vivo;information processing;insight;Intellectual functioning disability;Kinetics;Knock-out;Knockout Mice;Link;Location;Mammals;Medial;Molecular;mouse model;Mus;Music;mutant;Mutation;Nervous System;Nervous System Disorder;Neurons;neuropsychiatric disorder;neurotransmission;novel;operation;P-Q type voltage-dependent calcium channel;Pathologic;Pathway interactions;Pattern;Physiological;presynaptic;Presynaptic Terminals;Probability;Process;Publishing;Regulation;Research;response;Role;Signal Transduction;Slice;sound;Sound Localization;Source;Speech;Speech Perception;Speech Sound;Spike Potential;Stimulus;Synapses;synaptic depression;Synaptic plasticity;Synaptic Transmission;Synaptic Vesicles;Techniques;Testing;therapy development;transmission process;trapezoid body;vesicular release;Viral Vector;voltage;Whole-Cell Recordings

PROJECT_TITLE: Regulation of Synaptic Vesicle Dynamics in the Auditory System


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Machine Learning and Artificial Intelligence;Precision Medicine;Primary Immunodeficiencies;Rare Diseases

ORG_DEPT: DERMATOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative This project addresses the imperative needs of hidradenitis suppurativa (HS) patients who suffer from pain, stigma, diminished quality of life, decreased work productivity, and increased healthcare costs that arise from managing a difficult-to-treat, debilitating disease with a high burden of comorbidities. We will conduct studies of HS comorbidities to identify biologically distinct subclasses of HS in large samples of patients using data in electronic health records and data collected from Internet surveys. This work will improve the precision of HS diagnoses and set up the infrastructure for future large-scale studies of HS.

PI_NAMEs: PETUKHOVA, LYNN  (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Abscess;Address;Advertising;Affect;All of Us Research Program;Anogenital region;arm;Automobile Driving;Axilla;Biological;Biology;biomedical informatics;Biometry;Caring;Chronic;Cicatrix;Clinical;clinical diagnosis;Code;cohort;Communities;comorbidity;Complement;Consent;Data;Data Reporting;data repository;data resource;data sharing;design;Development;Diagnosis;Diagnostic;diagnostic tool;Disease;Disease Outbreaks;disorder subtype;Disparate;Economic Burden;effective therapy;Electronic Health Record;Electronic Medical Records and Genomics Network;Enrollment;Epidemiology;Etiology;Funding;Furuncles;Future;Genetic;Genetic Risk;Genome;genome wide association study;Goals;Health;Health Care Costs;health care service utilization;health data;Healthcare;Heterogeneity;Hidradenitis Suppurativa;Human Genetics;improved;Individual;individual patient;Infrastructure;Inguinal region;instrument;International Classification of Disease Codes;Internet;Investments;Knowledge;large datasets;learning strategy;Leg;Lesion;Link;Liquid substance;Literature;Longitudinal cohort;Maps;Medical;medically underserved;member;Mendelian randomization;Methods;Molecular Biology;Molecular Diagnosis;multidimensional data;Mutation;National Human Genome Research Institute;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;neglect;online resource;Pain;Participant;Pathogenesis;patient engagement;patient stratification;patient subsets;Patients;Pattern;Phenotype;Physiological;Population;Practice Guidelines;precision medicine;Precision Medicine Initiative;Prevalence;prevent;Productivity;programs;psychosocial;Publishing;Quality of life;Recording of previous events;Records;recruit;Recurrence;Research;Research Design;Research Methodology;Research Personnel;research study;Research Training;Resources;Sampling;Site;skin disorder;social media;social stigma;Stigmatization;Subgroup;Surveys;symptom self management;Symptoms;Syndrome;Testing;Time;Training;translational potential;Translational Research;Treatment outcome;United States National Institutes of Health;Universities;unsupervised learning;Validation;validation studies;Work

PROJECT_TITLE: Identification of biologically relevant subtypes of hidradenitis suppurativa

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurodegenerative;Neurosciences;Precision Medicine;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Early detection of neurocognitive disorders is highly beneficial for patients and families, yet cognitive impairment and dementia are frequently under-recognized. The UCSF Brain Health Assessment is a promising paradigm to rapidly detect cognitive impairment and provide turnkey guidance for follow-up. The proposed research will evaluate the effectiveness of the paradigm for improving brain health care via a large pragmatic trial, address challenges to implementation, and pioneer precision medicine approaches to reference group adjustments.

PI_NAMEs: POSSIN, KATHERINE LAUREL (contact)

PROGRAM_OFFICER_NAME: HOMMER, REBECCA EVE

PROJECT_TERMS: Address;Adoption;African American;Aging;Algorithms;Alzheimer's Disease;Asian;Black race;brain health;California;care outcomes;Caring;Classification;Clinical Pathways;Cluster randomized trial;cohort;Consultations;Dementia;Detection;Diagnosis;Diagnostic;Disclosure;Early Diagnosis;effectiveness evaluation;ethnic disparity;ethnic diversity;experience;Family;follow-up;Fund Raising;Funding;Goals;health assessment;health care disparity;health disparity;Healthcare;Hispanic;human old age (65+);Impaired cognition;Impairment;implementation barriers;improved;Individual;Integrated Health Care Systems;Latino;member;National Institute of Neurological Disorders and Stroke;neurocognitive disorder;novel;novel strategies;Nurse's Role;Nurses;older adult;Outcome;Pacific Islander;parent project;Parents;Patients;Population;Population Heterogeneity;pragmatic trial;precision medicine;Primary Care;primary care clinic;Primary Care Physician;racial disparity;Randomized;rapid detection;Registered nurse;Research;San Francisco;Social Adjustment;social determinants;social health determinants;Spanish/English;Tablets;Team Nursing;Testing;treatment as usual;treatment effect;Universities;user-friendly;Waiting Lists;Work

PROJECT_TITLE: Augmenting Nurse Support and EHR Integration for the Pragmatic Trial of the UCSF-BHA


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: NEW HAVEN

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: YALE UNIVERSITY

PHR: Project Narrative The described structure-function studies of riboswitches in bacteria will contribute to the development of strategies to target these RNAs that control essential genes in human pathogens for antibiotics development. The described structure-function studies of CRISPR interference system in bacteria will contribute to the development of strategies to manipulate the CRISPR-Cas operon to control the proliferation and virulence of microbial pathogens. Novel genome editing applications will be derived from the proposed mechanistic studies.

PI_NAMEs: KE, AILONG  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Adopted;Antibiotics;Area;Bacteria;Bacterial Physiology;Biochemical;Biological Process;Biology;Biophysics;Biotechnology;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR interference;Development;Essential Genes;Eukaryota;Gene Expression Regulation;Genetic Screening;genome editing;genomic tools;human pathogen;Immunity;insight;Integrase;Investigation;Ligands;Mediating;Medicine;Molecular Conformation;Molecular Genetics;novel;Operon;Orphan;pathogenic microbe;Proliferating;Proteins;Research;Resolution;RNA;RNA Interference;Structure;System;Virulence;Work

PROJECT_TITLE: Mechanistic Investigation of RNA-Mediated Gene Regulation and Immunity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-Q(55)R]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Neurosciences;Physical Activity;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Spinal Cord Injury;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human;Transplantation;Traumatic Head and Spine Injury

ORG_CITY: COLUMBIA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: Narrative A high-level spinal cord injury (SCI) interrupts supraspinal regulation of sympathetic activity to the heart. The imbalance of sympathetic and parasympathetic outflow leads to cardiac and hemodynamic disorders. In this project, we will determine whether integration of transplanted raphe nucleus-derived neural progenitor cells (RN-NPCs) or human induced pluripotent stem cell (iPSC)-derived serotonergic progenitors with spinal cord circuitry reestablishes serotonin regulation to improve cardio-electric transduction. Meanwhile, we will test whether combining RN-NPC transplants with exercise further enhances the reconstruction of sympathetic regulation to restore cardiac activity, hemodynamics, and autonomic dysreflexia after SCI. The results will provide vital guidance to future clinical therapeutics.

PI_NAMEs: HOU, SHAOPING  (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Adult women;Animals;Arrhythmia;Autonomic Dysreflexia;Axon;axon regeneration;Blood Pressure;Brain Stem;Cardiac;Cardiovascular system;Cells;Chronic;Clinical;colorectal distension;combinatorial;comorbidity;Control Groups;Coronary heart disease;Disease;Dobutamine;effective therapy;Embryo;Embryo Transfer;Exercise;Fostering;FRAP1 gene;Functional disorder;Future;Genetic;Green Fluorescent Proteins;Growth;Heart;Heart Diseases;Heart failure;heart function;heart rate variability;hemodynamics;Hindlimb;Histologic;human induced pluripotent stem cells;Hypotension;Implant;improved;Inbred F344 Rats;Incidence;Injury;insight;Interneurons;Interruption;Intervention;Kidney;Lesion;Longitudinal Studies;Modeling;mortality risk;Myocardial dysfunction;nerve stem cell;Neurons;neurotrophic factor;novel;Nuclear Pore Complex;Orthostatic Hypotension;Pathway interactions;pharmacologic;Production;progenitor;raphe nuclei;Rat Transgene;Rattus;receptor;reconstitution;reconstruction;Recovery;Recovery of Function;recruit;Regulation;Reporting;Rest;Role;serotonergic regulation;Serotonergic System;Serotonin;Signal Transduction;Site;Spinal;Spinal Cord;Spinal cord injury;Spinal Cord transection injury;Stem cell transplant;stem cells;Synapses;Testing;Thallium Myocardial Perfusion Imaging Stress Test;Therapeutic;Therapeutic Intervention;translational potential;Transplantation;Western Blotting

PROJECT_TITLE: Combining Serotonergic Neural Progenitor Transplantation and Exercise to Improve Cardiac Disorders and Autonomic Dysreflexia After Spinal Cord Injury

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: EAST LANSING

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative The proposed project is relevant to public health because communicating effectively to African Americans about SARS-CoV-2 antibody testing, as well as providing an option of at-home non-invasive antibody screening in saliva, could enhance uptake of antibody testing among African Americans – a racial minority population that has been especially impacted by the COVID-19 pandemic. Greater uptake of antibody testing among African Americans is also critical to better grasping how inflammatory process contribute to racial disparities in SARS-CoV-2 infection and recovery. The proposed research is relevant to the NCI mission to conduct and fund research that improves early detection and diagnosis and reduces cancer-related disparities.

PI_NAMEs: LUCAS, TODD WILLIAM (contact)

PROGRAM_OFFICER_NAME: LAM, TRAM K

PROJECT_TERMS: 2019-nCoV;African American;African American population;Antibodies;Attitude;Biological Assay;Biological Markers;Biological Process;Biological Sciences;Cities;Clinical;Cognition;Collaborations;Collection;Communication;Communities;community partners;COVID-19;COVID-19 disparity;COVID-19 pandemic;COVID-19 pandemic effects;Disparity;Early Diagnosis;experience;Funding;Goals;grasp;health communication;Health Resources;Home;improved;Inflammation;Inflammatory;Inflammatory Response;innovation;insight;Knowledge;Malignant Neoplasms;Measures;Medical;Methods;Michigan;Mission;Process;programs;Public Health;Race;racial disparity;racial minority population;racial population;racism;Recovery;Registries;Research;Role;Route;Saliva;Salivary;salivary assay;SARS-CoV-2 antibody;SARS-CoV-2 infection;screening;stem;Testing;United States;uptake

PROJECT_TITLE: Supplement to U01CA260469


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Lung;Lung Cancer;Orphan Drug;Precision Medicine;Rare Diseases

PI_NAMEs: POLITI, KATERINA ABIGAIL (contact)

PROGRAM_OFFICER_NAME: UJHAZY, PETER

PROJECT_TERMS: 3-Dimensional;acquired drug resistance;Address;analytical method;Animal Model;Award;Biology;cancer cell;Cancer cell line;Cell Culture Techniques;Cells;Characteristics;Chromatin;Dependence;Development;Drug resistance;Effectiveness;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Epigenetic Process;epigenome;experimental study;Fostering;Gene Dosage;Genetic;Genome;Human;In Situ;Individual;Knowledge;Lung Adenocarcinoma;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Methods;Molecular Conformation;mouse model;mutant;Mutation;Neoplasm Metastasis;new therapeutic target;novel;Oncogenes;Parents;patient derived xenograft model;Patients;personalized medicine;pharmacologic;predictive marker;Prognostic Marker;Resistance;resistance mechanism;Role;stemness;targeted treatment;three-dimensional visualization;Tissues;Tumor Suppressor Genes;Tyrosine Kinase Inhibitor

PROJECT_TITLE: Project 2: Mechanism-based approaches to counter TKI resistance in EGFR mutant lung cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 TCRB-D (M2)]


ORG_CITY: CORAL GABLES

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: NARRATIVE Our studies identified specific Guanine nucleotide Exchange Factors (GEFs) for the small G-protein Rac1 expressed in human lung adenocarcinoma cells that were required for their motility and invasive activities. The goal is to elucidate the involvement of these Rac-GEFs in disease progression. We will generate animal models to determine their roles in metastasis and examine at a mechanistic level their relationship with oncogenic KRAS and EGFR.

PI_NAMEs: KAZANIETZ, MARCELO G. (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Actins;Address;Adenocarcinoma;Adenocarcinoma Cell;Animal Model;Automobile Driving;Bioinformatics;Biological Markers;Blood Cells;cancer cell;Cancer cell line;Cancer Etiology;cancer invasiveness;Cancer Patient;Cell Line;Cell model;cell motility;Cell Separation;Cells;Cessation of life;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;Decision Making;Development;Disease;Disease Outcome;Disease Progression;EGF gene;Epidermal Growth Factor Receptor;experimental study;Extracellular Matrix;Extracellular Matrix Degradation;Family;Gene Expression;Gene Expression Profile;gene-editing approach;Genes;genetic signature;Goals;Growth Factor;GTP Binding;Guanine Nucleotide Exchange Factors;Guanosine Triphosphate;Histologic;Human;Human Cell Line;in vivo;Individual;Invaded;KRAS oncogenesis;KRAS2 gene;KRASG12D;LoxP-flanked allele;Lung;Lung Adenocarcinoma;lung cancer cell;lung metastatic;Malignant - descriptor;Malignant neoplasm of lung;Malignant Pleural Effusion;Mediating;Mediator;member;Modeling;Monomeric GTP-Binding Proteins;Motility;Mouse Cell Line;mouse model;Mus;mutant;Mutation;mutational status;Nature;Neoplasm Circulating Cells;Neoplasm Metastasis;neoplastic cell;Newly Diagnosed;Non-Small-Cell Lung Carcinoma;novel;Oncogenic;Outcome;Pathway interactions;patient prognosis;Patients;Peptide Hydrolases;peripheral blood;permissiveness;Phenotype;Play;Population;Primary Neoplasm;Production;Prognosis;Protein Isoforms;rac1 GTP-Binding Protein;Receptor Protein-Tyrosine Kinases;rho;Role;Sampling;screening;Signal Transduction;Site;Specimen;Structure;TACSTD1 gene;TIAM1 gene;TP53 gene;transcriptome;translational potential;tumor;Tumor Cell Line;tumor heterogeneity;tumor progression;tumorigenesis;Up-Regulation

PROJECT_TITLE: Rac guanine nucleotide exchange factors in lung cancer

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


NIH_SPENDING_CATS: Aging;Physical Activity

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Narrative: This program project renewal will continue to identify the molecular mechanisms whereby bone and muscle communicate independent of mechanical loading of bone by muscle. The underlying premise for these studies is that bone cells secrete circulatory factors that regulate muscle mass and function and in turn, secreted factors from contracted muscle can maintain bone cell viability and function. The negative effects of aging on this “muscle-bone crosstalk” are attenuated by normal physiological exercise so identification of these molecular mechanisms should lead to therapeutics for the twin condition of “osteo-sarcopenia”..

PI_NAMEs: BONEWALD, LYNDA F (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Acceleration;age effect;Aging;Attenuated;beta catenin;bone;bone cell;bone mass;Brain;Cell Line;Cell Physiology;Cell secretion;Cell Survival;Communication;Contracts;Disease;Engineering;Estrogens;Exercise;extracellular vesicles;Functional disorder;Health;heart function;imaging capabilities;Immobilization;Individual;interdisciplinary approach;Intervention;intravital imaging;lipidomics;live cell imaging;Maintenance;mechanical load;Metabolism;metabolomics;Molecular;mouse model;Movement;Muscle;Muscle Cells;Muscle Contraction;muscle form;Muscle function;Musculoskeletal Diseases;Musculoskeletal System;myogenesis;Organ;Organism;Osteoblasts;Osteocytes;Physiological;prevent;programs;Regulation;Role;sarcopenia;sedentary;Societies;success;System;Testing;Therapeutic;Transgenic Mice;Twin Multiple Birth

PROJECT_TITLE: OSTEOCYTE REGULATION OF BONE/MUSCLE WITH AGING


ORG_CITY: Columbus

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Overall Project Narrative The Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID) is proposed as a transdisciplinary center that will provide infrastructure to understand how risk, transmission, and mitigation practices impact antibody responses, immune protection, and disease severity in people infected with SARS-CoV-2. A key component of the Center will be a long-term study of Columbus first responders and their household contacts, a group who are at continual high risk for exposure and re-exposure. Insights from these serological studies will inform new strategies for communication of test results and their implications to reduce access barriers to testing and vaccination, ultimately improving clinical and population health outcomes.

PI_NAMEs: MCALEARNEY, ANN SCHECK;OLTZ, EUGENE M (contact);PANCHAL, ASHISH RAMAN;SAIF, LINDA J.

PROGRAM_OFFICER_NAME: CARRICK, DANIELLE M

PROJECT_TERMS: 2019-nCoV;Address;Antibodies;Antibody Response;Antigens;Applied Research;barrier to testing;Basic Science;Behavioral;biobank;Bioinformatics;Biological Assay;Biometry;Clinical;cohort;Common Cold;Communication;Coronavirus;Cost Sharing;COVID-19;COVID-19 impact;COVID-19 pandemic;COVID-19 prevalence;COVID-19 severity;Data;Data Analyses;data management;data sharing;Disease;Disease Outcome;Enzyme-Linked Immunosorbent Assay;Epidemiology;first responder;Genetic;Goals;high risk;Household;Immune;Immune response;implementation strategy;improved;improved outcome;Individual;Infrastructure;innovation;insight;Leadership;Longitudinal Studies;Molecular;Monoclonal Antibodies;novel;Outcome;parent grant;parent project;Pathogenesis;Persons;population health;Psychometrics;Reagent;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;respiratory virus;response;Risk;Role;SARS-CoV-2 exposure;SARS-CoV-2 infection;Serology;Serology test;Severity of illness;stem;Test Result;Testing;transcriptomics;Translational Research;Translations;transmission process;Vaccination;Vaccines;Viral;virus testing;Work

PROJECT_TITLE: Center for serological testing to improve outcomes from pandemic COVID-19 (STOP-COVID)


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Liver Disease

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: NARRATIVE A successful Program Project Grant (PPG) relies heavily on an outstanding scientific program that is supported by an equally outstanding Administrative Core (Core A). Core A will (1) provide scientific, administrative, fiscal, and organizational coordination of all the activities of the Projects and Cores, (2) facilitate interactions and data sharing, and (3) provide oversight and strategic planning and evaluation for the program as a whole. Core A is an essential component of the PPG to allow the PPG investigators to achieve their scientific goals.

PI_NAMEs: LU, SHELLY CHI-LOO (contact)

PROJECT_TERMS: Award;Budgets;Collection;Committee Members;data sharing;Ensure;Evaluation;Expenditure;Goals;Leadership;meetings;member;Metastatic Neoplasm to the Liver;Monitor;Organizational Efficiency;Preparation;Program Evaluation;Program Research Project Grants;programs;Progress Reports;Protocols documentation;Publications;Reagent;Reporting;Research Personnel;Solid Neoplasm;Strategic Planning;Writing

PROJECT_TITLE: Core A: Administration


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Lung;Lung Cancer

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative This grant application develops new and innovative technologies for applications in lung cancer bronchoscopy and surgery. The main goal is to aid the clinician in delineating tumor margins, identifying diseased lymph nodes and micrometastases, and determining if the tumor has been completely resected. A cocktail of innovative targeted optical contrast agents for lung cancer is expected to generate a major impact in the diagnosis and treatment of this disease.

PI_NAMEs: SINGHAL, SUNIL  (contact)

PROGRAM_OFFICER_NAME: TANDON, PUSHPA

PROJECT_TERMS: Acceleration;Address;Adjuvant Therapy;American;Applications Grants;Back;Binding;Biopsy;body cavity;Bronchoscopy;cancer cell;Cancer Patient;cancer surgery;Cancerous;capsule;Cells;Clinic;Clinical;clinical application;Clinical Trials;Colonoscopy;Colposcopy;Contrast Media;Cystoscopy;Deposition;Detection;Devices;Diagnosis;Diagnostic;diagnostic accuracy;Disease;Dose;draining lymph node;Endoscopy;Equipment;Esophagoscopy;Excision;experience;first-in-human;flexibility;FOLR1 gene;Genomics;Goals;Grant;healthy volunteer;Histologic;Histology;Human;Image;image guided;Image-Guided Surgery;Imaging Device;improved;Individual;Infusion procedures;innovation;innovative technologies;Institution;Laparoscopy;Lesion;Localized Disease;Location;Lung;Lung nodule;lymph nodes;Malignant neoplasm of lung;Malignant Neoplasms;Measures;Medical Imaging;Micrometastasis;molecular imaging;Motion;Near-infrared optical imaging;new technology;Nodule;Non-Small-Cell Lung Carcinoma;novel;Operating Rooms;operation;Operative Surgical Procedures;optical imaging;Optics;Pathologic;Patient imaging;Patients;Penetration;Pennsylvania;Phase;Polyps;Predictive Value;Procedures;Pulmonary Pathology;radiological imaging;receptor;Resectable;Resected;Residual Cancers;Residual state;Resolution;respiratory;Second Primary Cancers;Series;Solid Neoplasm;Specificity;Specimen;Staging;standard of care;success;Surgeon;Technology;Testing;Therapeutic;Thoracic Surgical Procedures;Time;Tissues;Tracer;Translating;Translations;tumor;Universities;Validation;Visual;Work;wound bed

PROJECT_TITLE: Project 1: Clinical Trials in Intraoperative Molecular Imaging of Non-Small Cell Cancer


ORG_CITY: SAN JUAN

ORG_NAME: UNIVERSITY OF PUERTO RICO MED SCIENCES

ORG_STATE: PR

PHR: NARRATIVE As newer versions of vaccines are adapted to recent SARS-CoV-2 variants (i.e., bivalent vaccines andXBB1.5), we must continue to determine how effective these vaccines are overtime against emerging variants and establish how vulnerable populations like Latino/Hispanic and others are still responding. We will characterizes the kinetics, magnitude, and durability of type-specific neutralizing antibody and T cells responses to different current SARS-CoV-2 variants after natural infection or vaccination, designed to reveal correlates associated with protective immunity or disease severity or progression to long COVID.

PI_NAMEs: BRIEN, JAMES D;LOPEZ, MARCOS ;SARIOL, CARLOS A (contact);WEISKOPF, DANIELA

PROGRAM_OFFICER_NAME: MARQUEZ, GUILLERMO

PROJECT_TERMS: 2019-nCoV;adaptive immune response;adaptive immunity;African American;Age;Antibodies;Antibody Response;Antibody titer measurement;antigen-specific T cells;Antigens;Appearance;Area;Autoimmune Diseases;B-Lymphocytes;biobank;booster vaccine;breakthrough infection;CD4 Positive T Lymphocytes;Cell Culture Techniques;Cells;Communicable Diseases;Communities;comorbidity;COVID-19 pandemic effects;COVID-19 severity;COVID-19 vaccine;cross reactivity;cytokine;design;Development;Diagnostic;diagnostic platform;Disease Outcome;Disease Progression;Dissection;Dose;Emergency response;Evaluation;Event;Formulation;Funding;Gender;Hematopoietic Stem Cell Transplantation;high risk;Hispanic;IgG4;Immune;Immune response;Immunity;Immunoglobulin G;Immunoglobulin-Secreting Cells;Immunologics;immunopathology;Immunotherapy;In Vitro;Individual;Infection;Kinetics;Latino;Long COVID;Malignant Neoplasms;Measures;Memory;Monitor;Morbidity - disease rate;mortality;neutralizing antibody;novel;novel vaccines;Obesity;older adult;patient population;Patients;Peptides;Phenotype;Population;Populations at Risk;Prevalence;public health emergency;Puerto Rico;reconstitution;Report (document);Reporting;repository;Research;response;RNA vaccination;RNA vaccine;Role;Sampling;SARS-CoV-2 antibody;SARS-CoV-2 antigen;SARS-CoV-2 B.1.1.529;SARS-CoV-2 B.1.617.2;SARS-CoV-2 exposure;SARS-CoV-2 infection;SARS-CoV-2 variant;Serodiagnoses;Serology;severe COVID-19;Severity of illness;sex;Socioeconomic Status;symptomatology;Symptoms;T cell response;T-Lymphocyte;Time;Transplant Recipients;Transplantation;Underrepresented Populations;United States;unvaccinated;Vaccinated;Vaccination;vaccination outcome;Vaccine Design;vaccine immunogenicity;Vaccines;Variant;variant of interest;Viral;Virus;Vulnerable Populations;Work

PROJECT_TITLE: SARS-CoV-2 correlates of protection in a Latino-origin population


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Genetics;Kidney Disease;Pediatric;Precision Medicine;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: LAY NARRATIVE MCD, FSGS, MN, and IgAN are rare glomerular diseases of the kidney that cause serious illness including kidney failure and high mortality, generating enormous individual and societal burden. CureGN has assembled nephrologists, researchers with expertise in different scientific disciplines, and patients in a consortium that maintains and analyzes a large, longitudinal observational data and biosamples like blood, urine and images of kidney biopsies. This initiative has developed a critical infrastructure that will advance our ability to study, classify, characterize, diagnose, and treat primary glomerular diseases of the kidney.

PI_NAMEs: GADEGBEKU, CRYSTAL A.;MARIANI, LAURA H (contact);SMITH, ABIGAIL

PROGRAM_OFFICER_NAME: ROY, CINDY

PROJECT_TERMS: Acceleration;Achievement;actionable mutation;Address;Adult;Advocacy;Affect;Ancillary Study;APOL1 gene;biobank;Biocompatible Materials;Biology;biopharmaceutical industry;Biopsy;Blood;career development;Child;Childhood;Classification;Clinic;Clinical;clinical center;Clinical Data;Clinical Research;cohort;Collaborations;Collection;Communication;Communities;community engagement;Consultations;Data;Data Collection;data collection methodology;Data Coordinating Center;Databases;Development;Diagnosis;digital pathology;Discipline;Disease;Disease remission;Educational workshop;Electronic Health Record;Emerging Technologies;Enrollment;Ensure;Epigenetic Process;Etiology;Focal and Segmental Glomerulosclerosis;follow-up;Formalin;Fostering;Funding;Funding Agency;Future;Genetic;genome sequencing;Goals;Grant;Health Technology;Heterogeneity;high risk;high standard;IGA Glomerulonephritis;Immunologics;improved;Individual;Industry;industry partner;Infrastructure;innovation;International;Investigation;kidney biopsy;Kidney Diseases;Kidney Failure;kidney imaging;Knowledge;Longitudinal, observational study;Medical Record Linkage;Membranous Glomerulonephritis;metabolomics;Methods;mHealth;Michigan;Mission;mobile application;Modernization;Morbidity - disease rate;mortality;multidisciplinary;multimodal data;Natural History;Nephrology;next generation;North Carolina;novel;observational cohort study;Observational Study;Outcome;Output;outreach;pandemic disease;Paraffin Embedding;Participant;participant retention;Pathogenesis;Pathology;patient advocacy group;Patient Care;patient engagement;Patient Outcomes Assessments;Patient Participation;Patients;Pattern;Pennsylvania;personalized care;Persons;Phase;Pilot Projects;Population;precision medicine;predict clinical outcome;Procedures;Process;Productivity;Professional Organizations;Prognosis;programs;prospective;Protocols documentation;Publications;Publishing;recruit;Renal glomerular disease;repository;Research;Research Personnel;risk variant;Role;sample collection;Sample Size;Science;Scientist;Services;Site;social;social health determinants;Standardization;Statistical Data Interpretation;Structure;Time;Tissue Embedding;tool;Training;transcriptome sequencing;Translational Research;treatment response;treatment strategy;Universities;Urine;Visit;whole genome;Work;working group

PROJECT_TITLE: CureGN


NIH_SPENDING_CATS: Urologic Diseases;Women's Health Research

ORG_CITY: RESEARCH TRIANGLE PARK

ORG_NAME: RESEARCH TRIANGLE INSTITUTE

PHR: Project Narrative The PFDN was established in 2001 to improve the care of women with PFDs by conducting well- designed multicenter studies to inform diagnosis, prevention, and treatment. A qualified, experienced DCC is critical in helping the PFDN optimize research productivity through effective study design, implementation, data collection, quality assurance, monitoring, and statistical analysis. RTI will continue to provide multidisciplinary expertise to support high impact collaborative clinical research studies and provide communications and logistical support to optimize the efficiency and productivity of the Network.

PI_NAMEs: GANTZ, MARIE G (contact)

PROGRAM_OFFICER_NAME: TEPEDE, ABISOLA KAFAYAT

PROJECT_TERMS: Administrative Supplement;Caring;Clinical Research;Collection;Common Data Element;Communication;Communities;Data;Data Collection;Data Coordinating Center;data dissemination;data standards;design;Development;Diagnosis;experience;Funding;improved;instrument;Monitor;Multicenter Studies;multidisciplinary;National Institute of Child Health and Human Development;Pelvic Floor Disorders;Prevention;Productivity;Qualifying;quality assurance;Research;Research Design;research study;Standardization;Statistical Data Interpretation;Woman

PROJECT_TITLE: Pelvic Floor Disorders Network Data Coordinating Center Administrative Supplement: ODSS CDE Funding


ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF VIRGINIA

PHR: PROJECT NARRATIVE The proposed research is relevant to public health in that stroke and resulting disability represents an enormous burden in terms of not only mortality, but lifelong disability. Our work will explore a fundamental mechanism of secondary stroke progression, and is also expected to establish the groundwork for immediately testable, novel therapeutic approaches for stroke.

PI_NAMEs: CARLSON, ANDREW PHILLIP (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Acute;Brain;brain tissue;Clinical;Clinical Trials;Coupled;Critical Care;Data;disability;Early Mobilizations;Edema;Electrocorticogram;Electrodes;Electroencephalography;Event;Foundations;Future;Goals;hemodynamics;Human;human subject;Hyperthermia;Hypotension;Hypotensives;Hypoxia;improved;improved outcome;Infarction;insight;Intensive Care Units;Intervention;Ischemia;Ischemic Stroke;Life;Lifelong disability;Link;Measurement;Metabolic;Metabolic stress;Monitor;mortality;mouse model;Nervous System Trauma;Neurologic Examination;novel;novel therapeutic intervention;Outcome;Oxygen;Patient Care;Patients;Physical Stimulation;Physiological;Physiology;post stroke;pre-clinical;preclinical study;preservation;Public Health;Recovery;Research;Retrospective Studies;Risk;Risk Factors;standard of care;Stroke;stroke model;stroke outcome;stroke patient;Subarachnoid Hemorrhage;tactile stimulation;Testing;Therapeutic;Therapeutic Intervention;Time;tissue oxygenation;Tissues;Traumatic Brain Injury;Video Recording;Work

PROJECT_TITLE: Clinical Stimulation and Spreading Depolarization

STUDY_SECTION: ANIE

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


ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

PHR: NARRATIVE The proposed studies are in the area of electrical microstimulation for neuroprostheses, which has potential applications in many human diseases or injuries. Our work will further advance research by generating transformative and efficacious software and hardware technology that will be used widely throughout the research community. Thus, the proposed research is relevant to the translational focus of the NIH's mission and will potentially help to reduce the burdens of human disability.

PI_NAMEs: ORAZEM, MARK E.;OTTO, KEVIN J. (contact)

PROGRAM_OFFICER_NAME: HWANG, GRACE MEI-HUA

PROJECT_TERMS: Address;Area;Charge;Communities;Computer Models;Computer software;design;disability;Electric Stimulation;electrical microstimulation;Elements;Engineering;Evaluation;Goals;Human;human disease;in vivo;Injury;innovation;Measurement;Microelectrodes;microstimulation;Mission;Modeling;Nervous System;neural;Neurons;neuroprosthesis;neuroregulation;Neurosciences;Outcome Assessment;Performance;Research;Resolution;response;Technology;temporal measurement;Testing;tool;United States National Institutes of Health;user-friendly;Work

PROJECT_TITLE: Engineering the Neuronal Response to Electrical Microstimulation


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Foodborne Illness;Genetics;Human Genome;Prevention

ORG_CITY: CHICAGO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Over one hundred million people worldwide consume arsenic-contaminated drinking water, which increases risk for a wide array of health conditions, including cancer. The goal of this project is to identify features of the human genome, both inherited and acquired, that reflect susceptibility to arsenic toxicity or response to arsenic exposure, using data from a large arsenic-exposed Bangladeshi cohort. Achieving these goals will reveal biological mechanisms of toxicity and susceptibility, identify potential targets for pharmacological intervention, and provide strategies for identifying high risk individuals and reducing their exposure.

PI_NAMEs: PIERCE, BRANDON LEE (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Arsenic;Arsenicals;Bangladesh;Bangladeshi;Behavior;Biological;Biological Markers;biomarker identification;cancer type;Cardiovascular Diseases;Chromosomal Loss;cohort;Consumption;contaminated drinking water;Data;Disease;DNA Methylation;drinking water;Environment;Environmental Health;Epidemiology;epidemiology study;epigenetic aging;Exposure to;Food Contamination;gene environment interaction;Genes;Genetic;genetic information;Genetic Predisposition to Disease;Genetic study;Genome;genome resource;genome wide association study;genome-wide;Genomics;global health;Goals;Health;Heritability;high risk population;Human;Human Genome;Individual;Inherited;Intervention;Knowledge;Length;life span;Malignant Neoplasms;Measurement;Metabolism;mitochondrial DNA mutation;Non-Malignant;novel marker;Outcome;Participant;Persons;pharmacologic;Point Mutation;Predisposition;Reproducibility;Research;Resources;Respiratory Disease;response;Risk;Role;Rural;skin lesion;Subgroup;Technology;telomere;Testing;Toxic effect;Variant;Work

PROJECT_TITLE: Arsenic and the Human Genome:  susceptibility and response to exposure


NIH_SPENDING_CATS: Aging;Genetics;Hematology;Human Genome;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Human

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: NARRATIVE We aim to investigate the role of clonal hematopoiesis (CH) in neurodegenerative diseases. Recent research highlights CH protective effect against Alzheimer's, underscoring the need for a comprehensive exploration across various neurodegenerative diseases. Using innovative methods and abundant sequencing datasets, we aim to uncover CH's complex implications, potentially informing tailored therapies and predictive biomarkers.

PI_NAMEs: RAJ, TOWFIQUE  (contact)

PROGRAM_OFFICER_NAME: RAGHAVACHARI, NALINI

PROJECT_TERMS: age related;Alzheimer's Disease;Alzheimer's disease risk;ATAC-seq;Automobile Driving;autosome;Biological Markers;biomarker discovery;Brain;cancer risk;Cardiovascular Diseases;case control;Categories;Cell Nucleus;cell type;Cells;Central Nervous System;Characteristics;Chromatin;Chromosomal Loss;Chromosome abnormality;chromosome Y loss;Clonal Expansion;cohort;Complement;Complex;Data;Data Set;Dementia with Lewy Bodies;Development;Disease;Disease Progression;Disparity;Epigenetic Process;Etiology;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;functional genomics;Genes;Genetic Transcription;genome sequencing;genomic data;Genotype;Hematopoiesis;hematopoietic stem cell expansion;Hematopoietic System;High-Throughput Nucleotide Sequencing;Human;Individual;individualized medicine;induced pluripotent stem cell;innovation;insight;Investigation;Knowledge;Link;Macrophage;Malignant Neoplasms;Mendelian randomization;Methods;Microglia;mosaic;Mosaicism;mutant;Mutation;Myelogenous;Myeloid Cells;Myeloproliferative disease;Neurodegenerative Disorders;novel;Parkinson Disease;Pathogenesis;Patients;predictive marker;protective effect;Publishing;Reporting;Research;Risk;risk prediction;Role;Sampling;Sex Chromosomes;single nucleus RNA-sequencing;single-cell RNA sequencing;Somatic Mutation;Sorting;stem;stem cells;Tissues;transcriptome;transcriptomics;whole genome;Work

PROJECT_TITLE: Unraveling the Role of Clonal Hematopoiesis in Neurodegenerative Diseases


ACTIVITY: ZIA

ADMINISTERING_IC: CL

FUNDING_MECHANISM: INTRAMURAL RESEARCH

IC_NAME: CLINICAL CENTER

ORG_NAME: CLINICAL CENTER

PI_NAMEs: MASUR, HENRY  (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adherence;Affect;Agonist;Agreement;AIDS prevention;Alabama;Amphetamines;Anti-Retroviral Agents;Award;Bacterial Endocarditis;Cardiovascular Diseases;Caring;Characteristics;Cities;Clinic;Clinical;Clinical Research;clinical research site;Cocaine;cohort;Cohort Studies;Collaborations;Communicable Diseases;Communities;comorbidity;craving;Data Analyses;Databases;Death Rate;design;Development;Disease;disenfranchised population;District of Columbia;Dopamine;Drops;drug development;Emergency department visit;Enrollment;Epidemic;experience;Funding;Goals;Grant;Health;health care service organization;Health Policy;Health Services Accessibility;healthcare community;Hepatitis C;Hepatitis C Therapy;Hepatitis C Transmission;Hepatitis C virus;Hepatotoxicity;high risk;HIV;HIV Infections;HIV Seropositivity;HIV therapy;HIV/AIDS;HIV/HCV;hormone therapy;Hospital complications;Hospitalization;Human Papilloma Virus-Related Malignant Neoplasm;improved;Incidence;Infection;injection drug use;innovation;inpatient service;Intention;Intervention;Joints;Kidney Diseases;Lead;Leadership;Link;Liver diseases;Malignant Neoplasms;marginalization;marginalized population;Maryland;Medical;meetings;member;Metabolic Diseases;methamphetamine abuse;Mission;Molecular;Molecular Epidemiology;Morbidity - disease rate;National Institute of Allergy and Infectious Disease;National Institute of Drug Abuse;National Institute of Mental Health;National Institute of Neurological Disorders and Stroke;Needs Assessment;novel;novel strategies;operation;Opioid;opioid use disorder;outpatient programs;Overdose;overdose death;Pathway interactions;Patient Admission;Patient Care;patient engagement;Patients;Persons;Pharmaceutical Preparations;Pharmacologic Substance;Phase;phase 1 study;Population;Prevalence;Prevention;primary medical care;programs;Protocols documentation;Provider;Public Health Schools;Publications;Publishing;Research;research study;Risk Behaviors;Role;Services;sex;Sexually Transmitted Diseases;Site;Stimulant;Subgroup;Substance Use Disorder;success;Testing;Therapeutic;Tobacco Use Cessation;Toxic effect;transgender;transmission process;Underinsured;Underserved Population;United States National Institutes of Health;Universities;urban area;Viral;Virus Diseases;volunteer;Washington

PROJECT_TITLE: DC Partnership for HIV/AIDS Progress (DC PFAP)


PI_NAMEs: FRANK, JOSEPH  (contact)

PROJECT_TERMS: 4 year old;4T1;Acceleration;Acoustics;Acute;Adolescent;Adult;Aging;anakinra;Area;B-Cell Activation;Biological;Bladder Calculi;bone;Calcium Channel;Cations;CCL2 gene;Cell Adhesion;Cell Adhesion Molecules;Cell membrane;Cell Therapy;Cells;chemokine;Chemotactic Factors;Chronic;Clinical;Complex;Contralateral;Coupled;Cues;cyclooxygenase 2;cytokine;Cytokine Signaling;Disparate;DNA Damage;Edema;Endothelium;Enhancers;Environment;Etanercept;Exhibits;Experimental Models;Fibrosis;Focused Ultrasound;Focused Ultrasound Therapy;Functional disorder;Gastrocnemius Muscle;Gene Expression;Goals;Homing;Hour;Human;Hydrogen Peroxide;Ibuprofen;Image;image guided;Immune;immune cell infiltrate;Immune response;Immunity;implantation;Inflammaging;Inflammation;Inflammatory;Inflammatory Response;Infusion procedures;inhibitor;Innate Immune Response;Interleukin-1;Interleukin-15;Interleukin-6;Interleukins;interstitial;Investigation;Ion Channel;Kidney;Kidney Calculi;Laboratories;Light;Lithotripsy;Macrophage;Macrophage Colony-Stimulating Factor;Malignant Breast Neoplasm;Malignant Neoplasms;mechanical energy;Mechanics;mechanotransduction;Medicine;Melanoma;Membrane;mesenchymal stromal cell;Microbubbles;Molecular;monocyte;Mus;Muscle;muscle aging;muscular structure;neoplastic cell;neutrophil;Neutrophil Infiltration;NF-kappa B;novel;Nuclear;Nuclear Translocation;Pathway interactions;Pattern;Permeability;Physical Medicine;Physical therapy;Physiologic pulse;pre-clinical;precursor cell;Prednisone;pressure;Process;PTGS1 gene;Radiation;receptor;recruit;Reporter Genes;response;Signal Pathway;Signal Transduction;Skeletal Muscle;soft tissue;Sonication;stem;stem cells;Sterility;Structure;Superoxides;Testing;Therapeutic;Therapeutic Effect;Tissues;TNF gene;tool;Treatment Protocols;Tropism;Tubular formation;tumor;tumor microenvironment;ultrasound;ultrasound ablation;Uncertainty;Verapamil;voltage;Weight

PROJECT_TITLE: Preclinical high intensity focused ultrasound: mechanisms and applications


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Congenital Structural Anomalies;Genetics;Neurodegenerative;Neurosciences;Pediatric;Rare Diseases

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

PI_NAMEs: BONIFACINO, JUAN  (contact)

PROJECT_TERMS: Adaptor Protein Complex 2;Adaptor Signaling Protein;Alleles;anterograde transport;Architecture;Atrophic;Automobile Driving;Autophagocytosis;Axon;axonal degeneration;axonopathy;base;Binding;Biochemical;Biogenesis;Blood Coagulation Disorders;Blood Platelets;Brain;brain magnetic resonance imaging;Cell membrane;Cells;Central Nervous System;Child;Childhood;Clinical Trials;Collaborations;Complex;Congenital Abnormality;Congenital Disorders;Corpus Callosum;Cortical Cord;Cytoplasm;Cytoplasmic Granules;Defect;Development;Disease;Distal;Dysarthria;Electroencephalography;Endocytosis;Endoplasmic Reticulum;Endosomes;Epithelial Cells;Eukaryotic Cell;Evaluation;Exhibits;exome sequencing;Eye;Face;Facies;Failure;Family;Fibroblasts;fundamental research;gene therapy;Genes;Genetic;genetic disorder diagnosis;genomic locus;global developmental delay;Goals;Golgi Apparatus;Hereditary Spastic Paraplegia;Hermanski-Pudlak Syndrome;Heterozygote;Homeostasis;Human;human disease;human induced pluripotent stem cells;Impairment;improved;indexing;infancy;Infection;Integral Membrane Protein;Intellectual functioning disability;Intracellular Transport;Intrathecal Injections;Ion Channel;Kinesin;Knock-out;Knockout Mice;Knowledge;Laboratories;Lead;Length;Limb structure;Locomotion;loss of function;Lower Extremity;Lysosomes;Maintenance;Mediating;Melanosomes;Membrane;Membrane Proteins;Messenger RNA;Microtubules;Mitochondria;Molecular;Monomeric GTP-Binding Proteins;Motor;Multiprotein Complexes;Mus;Muscle hypotonia;Muscular Atrophy;Mutation;Names;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;Neurodevelopmental Disorder;neurogenetics;Neuroglia;Neurologic;neuromuscular;neuronal cell body;Neurons;nonhuman primate;novel;Optic Atrophy;Organelles;Oxidative Phosphorylation;Pathogenesis;Pathogenicity;Pathologic;Pathway Analysis;Pathway interactions;Patients;Peripheral;Phenotype;Phosphatidylinositols;Phosphorylation;Physiological;Physiological Processes;Pigmentation Disorders;Play;polarized cell;pre-clinical;prevent;Process;Protein Sortings;protein transport;Proteins;Protomer;Rattus;receptor recycling;recruit;Recycling;Regulation;retrograde transport;Ribosomes;RNA;RNA Transport;Role;Safety;Seizures;Signal Transduction;Sorting;Spastic Paraplegia;spasticity;Spinal Cord;Supratentorial;Symptoms;System;TFRC gene;Thinness;trait;trans-Golgi Network;Transfection;Translations;Tubular formation;Tyrosine;Variant;vector;Vesicle;vesicle transport;Work;Zebrafish

PROJECT_TITLE: Protein Trafficking In The Endosomal-Lysosomal System


NIH_SPENDING_CATS: Aging;HIV/AIDS;Infectious Diseases

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE As people with HIV grow older, they face health issues tied to inflammation, such as heart disease and cancer, even when the virus is controlled by antiretroviral therapy. This study aims to figure out what causes this inflammation, hypothesizing that the loss of specific anti-inflammatory carbohydrate molecules (glycans) circulating in the body contributes to the development of HIV-related inflammation, which could lead to associated health problems. The idea is that if changes occur in these glycan structures during the course of living with HIV, understanding these changes could open the door to identifying new biomarkers for predicting age-related illnesses in people with HIV, as well as developing novel strategies to correct these glycans and reduce inflammation.

PI_NAMEs: ABDEL MOHSEN, MOHAMED  (contact)

PROGRAM_OFFICER_NAME: TILAHUN, MULUALEM ENYEW

PROJECT_TERMS: Acceleration;Acute;age related;Aging;aging related;AIDS clinical trial group;Animals;Anti-Inflammatory Agents;Antibodies;antibody-dependent cell cytotoxicity;antiretroviral therapy;Attenuated;Binding;Biological Markers;biomarker identification;Blood;Carbohydrates;Cardiovascular system;Clinical;cohort;comorbidity;comparison control;Data;Development;Diagnosis;DNA;Engineering;Enzymes;Exhibits;Face;Fc Receptor;Funding;Galactose;General Population;Glycoengineering;Goals;Health;Heart Diseases;HIV;HIV Antibodies;HIV Infections;HIV Seronegativity;Human;humanized mouse;Immune;immune function;Immunity;Immunoglobulin G;Inflammaging;Inflammation;Inflammatory Response;inhibitor;innate immune function;Interruption;Link;Malignant Neoplasms;Mediating;Myeloid Cells;Neuraminidase;novel strategies;Outcome;Persons;Plasma;Polysaccharides;Prediction of Response to Therapy;predictive marker;prevent;pro-aging;Prognostic Marker;Sampling;Severities;Sialic Acids;sialylation;Structure;Testing;Tissues;translational potential;Viral;Virus;Work

PROJECT_TITLE: Glycomic Modulation of Inflammaging and Immune Functions during HIV Infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDB-X(02)]