ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Sleep Research;Women's Health Research

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE This project will address sex disparities in obstructive sleep apnea (OSA) severity that contribute to women being underdiagnosed with OSA compared to men. We will characterize OSA severity beyond conventional metrics such as the apnea-hypopnea index (AHI) and leverage sex differences in night-to-night variability in sleep and respiratory physiology to assess its temporal relationships with measures of ecological momentary assessments to improve how we define OSA severity for both women and men. We expect to identify sleep and respiratory traits that have biologically plausible effects on daytime function, to determine the role of sex on these associations, and thus to potentially challenge the current paradigm that the AHI defines OSA.

PI_NAMEs: MAZZOTTI, DIEGO ;MORRIS, JONNA  (contact)

PROGRAM_OFFICER_NAME: DIXIT, SHILPY

PROJECT_TERMS: accurate diagnosis;Affect;Age;Apnea;Architecture;Arousal;Attitude;Behavior;Biological Markers;cardiovascular disorder risk;Clinical;clinical heterogeneity;Data Collection;Diagnosis;Dimensions;Disease;disease heterogeneity;Disparity;Drowsiness;Ecological momentary assessment;effective therapy;Enrollment;Event;evidence base;Exclusion;expectation;Fatigue;Functional disorder;Gender;gender disparity;Goals;Guidelines;Health;Home;Hypoxia;Impairment;improved;indexing;Individual;Inequity;Kansas;Life;Literature;Long-Term Care;male;Measures;Mediating;Medical center;Medicine;men;Menopausal Status;Metabolic Diseases;Mood Disorders;Moods;novel;novel marker;novel strategies;Obstructive Sleep Apnea;Outcome;Participant;participant enrollment;Patient Self-Report;Physiological;Polysomnography;Protocols documentation;Pulse Rates;recruit;Research;research study;respiratory;Respiratory physiology;response;Role;Sampling;Severities;Severity of illness;sex;Sex Differences;sex disparity;Sleep;Sleep Apnea Syndromes;Sleep Architecture;sleep physiology;Sleep Stages;social culture;Source;standard measure;Stress;Structure;Symptoms;System;Technology;Testing;trait;Universities;Woman;women's outcomes

PROJECT_TITLE: Night- to-Night Variability in Sleep Disordered Breathing: Sex and Gender-Related Predictors and Impact on Obstructive Sleep Apnea Clinical Heterogeneity


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: Los Angeles

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: PROJECT NARRATIVE Alzheimer’s tau pathology follows a predictable path through the brain, starting in a small brainstem nucleus  called the locus coeruleus decades before any diagnosis. In this project, we test whether daily slow-paced  breathing sessions can promote a healthy pattern of locus coeruleus activity in Black and White adults ages  50-70.

PI_NAMEs: MATHER, MARA  (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Abeta synthesis;active control;Adult;Affect;Age;age related;aged;Aging;Alzheimer's Disease;Alzheimer’s disease biomarker;Anxiety;Arousal;Axon;Back;Baroreflex;Binding;Biological Markers;Black American;Black Populations;Black race;Blood Pressure;blood pressure elevation;blood pressure reduction;Blood Vessels;Brain;Brain Stem;Breathing;caucasian American;Cell Death;Cell Nucleus;Clinical Trials;Cognition;Cognitive;Data;Deposition;Diagnosis;Double-Blind Method;Early Intervention;Emotional;Emotions;Enrollment;entorhinal cortex;Event;Exhibits;Exposure to;Face;Feedback;Feeling;Fire - disasters;Frequencies;Functional Magnetic Resonance Imaging;functional MRI scan;Funding;Heart Rate;Hippocampus;Human;hyperphosphorylated tau;improved;Intervention;Intervention Studies;Learning;locus ceruleus structure;Magnetic Resonance Imaging;Mechanics;Memory;memory consolidation;memory encoding;Memory impairment;Memory Loss;Methods;Names;Neurobiology;Neurofibrillary Tangles;noradrenaline transporter;novel;older adult;optogenetics;Outcome;Participant;Pathology;Pathway interactions;Pattern;perceived discrimination;Phase;Phase II Clinical Trials;Play;Positron-Emission Tomography;post intervention;pre-clinical;Pressoreceptors;prevent;Procedures;Randomized;randomized trial;Rattus;response;Scanning;Shapes;Signal Transduction;Sorting;Stress;Stretching;Synaptic plasticity;tau Proteins;Testing;Time;Training;Wakefulness;Work

PROJECT_TITLE: Effects of Resonance-Frequency Breathing on Preclinical Alzheimer’s Disease Biomarkers and Cognition

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Genetics;Infectious Diseases;Lung;Pulmonary Fibrosis;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE  The association of idiopathic pulmonary fibrosis (IPF) with the scaffold protein osteopontin (OPN) is strong and consistent, but without considering the isoform variants of OPN, studies fail to fully elucidate their critical function in IPF promotion. This proposal will investigate the mechanism of intracellular OPN’s induction of fibrosis and its role in Trained Immunity, an innate memory program that may represent an immunological mechanism of IPF progression. This work will define a novel mechanistic understanding of OPN in IPF initiation and progression and has the potential to elucidate targeted therapeutic strategies.

PI_NAMEs: MESSERSCHMIDT, JONATHAN LEIGH (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Acute Lung Injury;Address;Adrenal Cortex Hormones;aerobic glycolysis;Alveolar;Alveolar Macrophages;ATAC-seq;Biochemical;Biological;Biological Assay;Biopsy;Bleomycin;candidate identification;Cells;Clinical;Collagen;Communicable Diseases;cytokine;Data;Dependence;Deposition;Development;Disease;Disease Progression;Epigenetic Process;epithelial injury;Etiology;Exhibits;experience;Extracellular Matrix;Fibroblasts;Fibrosis;FRAP1 gene;Functional disorder;Gene Expression;Genes;Genetic Predisposition to Disease;Glycolysis;Human;idiopathic pulmonary fibrosis;Immune;Immune signaling;Immunity;Immunologic Memory;Immunologics;improved;In Vitro;in vivo;in vivo Model;Inflammation;Inflammatory Response;Influenza;Injury;insight;Integrins;Interferon Type I;Interleukin 4 Receptor;Interleukin-4;Interstitial Lung Diseases;Ligation;lung injury;Lung Neoplasms;Macrophage;Mediating;Memory;Metabolic;Methods;Modeling;monocyte;mortality;mouse model;Mus;Myeloid Cells;new therapeutic target;novel;Oropharyngeal;osteopontin;Outcome;Oxidative Phosphorylation;pathogen;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Pattern recognition receptor;Peritoneal Macrophages;Personal Satisfaction;Phagocytosis;Phase;Phenotype;Phosphatidylinositols;Phosphotransferases;Production;programs;Protein Isoforms;Pulmonary Fibrosis;receptor;Receptor Signaling;Research;response;RNA analysis;Role;scaffold;Scaffolding Protein;Sclerosis;self-renewal;Severities;Signal Pathway;Signal Transduction;Source;Steroids;Study models;System;systemic inflammatory response;targeted treatment;Testing;therapeutic target;Training;transcriptome sequencing;Translations;Up-Regulation;Variant;Work;wound response

PROJECT_TITLE: Intracellular Osteopontin induces Pathologic Macrophage phenotypes in Pulmonary Fibrosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-R (08)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Caregiving Research;Dementia;Depression;Genetics;Mental Health;Mental Illness;Neurodegenerative;Neurosciences

ORG_DEPT: PHYSIOLOGY

PHR: Project Narrative Neuropsychiatric symptoms (NPS) frequently occur in individuals with Alzheimer’s disease (AD) and related dementias, causing significant distress to both patients and caregivers and often leading to early institutionalization. In this project, we will characterize pathological and molecular/cellular changes associated with NPS-like disturbances by utilizing well-established mouse AD models, and determine the potential underlying neural mechanisms. We hope that this project will generate new understanding of the relatively understudied neuropsychiatric impairments in AD, and can provide help for developing novel strategies for patient care and therapeutic approaches to mitigate deleterious impacts of NPS.

PI_NAMEs: TAO, HUIZHONG WHIT (contact);ZHAO, ZHEN

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: Acute;Affect;Aggressive behavior;Agitation;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease related dementia;Amyloidosis;Anatomy;Anterior;Anxiety;apolipoprotein E-4;Area;Autopsy;avoidance behavior;awake;base;Behavior;Behavior assessment;Behavioral;Behavioral Assay;behavioral impairment;Bioinformatics;Brain;Caregiver Burden;Caregivers;Categories;cell type;Chronic;cingulate cortex;Cognitive deficits;cognitive function;Collaborations;Disease;Disease Management;Disease Progression;Distress;Dose;Down-Regulation;Electrophysiology (science);Equilibrium;Exhibits;Foundations;Functional disorder;Genetic;genetic manipulation;Genetic Models;Genetic Transcription;Glutamates;Hyperactivity;Image;Impaired cognition;Impairment;Individual;Institutionalization;Lead;Location;Long-Term Effects;Mental Depression;Modeling;Molecular;Monitor;mouse genetics;mouse model;multidisciplinary;multimodal data;Mus;neocortical;neural;Neurofibrillary Tangles;neuroinflammation;neuromechanism;Neurons;Neurophysiology - biologic function;neuropsychiatric symptom;neuropsychiatry;Neuropsychology;novel strategies;operation;optogenetics;Oxidative Stress Pathway;Pathologic;Pathology;Patient Care;Patients;Personal Satisfaction;Predisposition;preference;Research;Rest;Rewards;Risk;Sampling;social;Social Interaction;statistics;Stress and Coping;Symptoms;tau Proteins;Testing;Therapeutic;Time;trait;transcriptomics;Up-Regulation

PROJECT_TITLE: Understanding Neural Bases for Neuropsychiatric Impairments in Alzheimer's Disease Models

STUDY_SECTION: PMDA

STUDY_SECTION_NAME: Pathophysiological Basis of Mental Disorders and Addictions Study Section[PMDA]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;HIV/AIDS;Health Services;Infectious Diseases;Mental Health;Pediatric;Pediatric - AIDS;Prevention;Sexually Transmitted Infections;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PI_NAMEs: KABAMI, JANE ;KOSS, CATHERINE ANNE STIMETS (contact)

PROGRAM_OFFICER_NAME: SENN, THERESA ELAINE

PROJECT_TERMS: Address;Adherence;Adoption;Affect;AIDS prevention;antenatal;care systems;Clinic;Clinical;Cluster randomized trial;Collaborations;Communities;community advisory board;community setting;cost;Cost Analysis;cost effectiveness;cost estimate;Counseling;Dapivirine;Data;Eastern Africa;effectiveness evaluation;effectiveness measure;empowerment;Enrollment;Equity;Face;Focus Groups;follow-up;General Population;girls;Guidelines;Hair;Health;Health care facility;HIV;HIV Infections;HIV risk;Household;Human immunodeficiency virus test;Hybrids;implementation strategy;implementation/effectiveness;Incidence;Infection;Injections;Intervention;intervention delivery;intervention effect;Interview;Knowledge;Location;Maintenance;Measures;Methods;Modality;Modeling;Motivation;next generation;opportunity cost;Oral;Outpatients;outreach;participant interview;patient oriented;Patient-Centered Care;peer;peer support;Persons;pill;pilot test;Policies;pre-exposure prophylaxis;Prevalence;Prevention;prevention service;preventive intervention;primary outcome;Prophylactic treatment;Provider;Randomized;randomized trial;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Research Infrastructure;Research Personnel;Risk;scale up;Scientist;self testing;Services;sex;social stigma;Southern Africa;standard of care;support tools;Surveys;Testing;testing services;Time;Training;Training Activity;transactional sex;Trust;Uganda;uptake;Urine;USAID;Vaginal Ring;Visit;Woman;women's prevention;Women's trial;Work;Working Women

PROJECT_TITLE: Peer-led Dynamic Choice HIV Prevention for Women at Elevated HIV Risk in Uganda

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 HSS-H (50)]


ADMINISTERING_IC: DA

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Drug Abuse (NIDA only);Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: NEW YORK

ORG_NAME: WE THE VILLAGE, INC.

ORG_STATE: NY

PHR: The goal of this project is to develop a scalable digital program to train behavioral addiction professionals (counselors) to high-fidelity levels in Community Reinforcement and Family Training (CRAFT) with the ultimate goal of increasing opioid use disorder (OUD) treatment entry rates. On average 68% of families coached in CRAFT achieve treatment entry for a loved one with OUD and this could help over 2 million Americans recover from OUD with effective treatment.

PI_NAMEs: MACKY, JANE  (contact)

PROGRAM_OFFICER_NAME: SABIRZHANOV, BORIS YEVGENYEVICH

PROJECT_TERMS: acceptability and feasibility;addiction;Address;Admission activity;Adopted;Adoption;Affect;American;Audiotape;Behavioral;care providers;Certification;Code;Collaborations;commercialization;Communities;comparison group;Continuing Education;cost;Data;Development;digital;digital delivery;Educational process of instructing;Educational Status;Educational workshop;effective therapy;Employment;evidence base;expectation;Family;Family member;FDA approved;Feedback;Goals;Health Personnel;Healthcare Systems;improved;Individual;induced pluripotent stem cell;Knowledge;Learning;Life;loved ones;Measures;medical specialties;Methods;Modeling;Multimedia;opioid use disorder;Outcome;overdose death;Persons;Pharmaceutical Preparations;Phase;Pilot Projects;prevent;Price;Procedures;Process;Professional counselor;programs;prototype;Psychological reinforcement;randomized trial;Randomized, Controlled Trials;Readiness;Recovery;Research;Resistance;retention rate;satisfaction;Secure;Standardization;Suggestion;supervised learning;Surveys;Testing;Time;Training;Training Programs;Translations;trial comparing;usability;Validation;Videoconferencing;Work;Writing

PROJECT_TITLE: Fast-track: Scalable digital delivery of evidence-based training for addiction professionals to maximize treatment admission and retention rates of opioid use disorder in affected families.


NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Cystic Fibrosis;Estrogen;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Women's Health Research

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Cystic fibrosis (CF) is characterized by thickened respiratory secretions, recurrent airway infection and neutrophilic inflammation resulting in progressive lung function decline; females with CF experience more pulmonary exacerbations and earlier mortality than males and show increased sputum inflammatory markers in association with high estrogen levels. This proposal will evaluate the effect of estrogen on neutrophil NET (neutrophil extracellular trap) release and inflammatory cytokine production and determine pathways involved using human cells, mouse models and samples from cis and transgender people with CF. The proposed research is relevant to public health because understanding how estrogen impacts neutrophilic inflammation in CF and non-CF bronchiectasis may help guide therapeutic targets, including nebulized estrogen receptor antagonists, and aims to decrease the sex disparity in CF and other chronic inflammatory respiratory diseases.

PI_NAMEs: JAIN, RAKSHA  (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Acceleration;Adult;Affect;Age;Agonist;Airway Disease;airway inflammation;antagonist;Asthma;Automobile Driving;Bacteria;Bacterial Infections;Biological Assay;Bronchiectasis;Cells;Cessation of life;Chronic;Chronic Obstructive Pulmonary Disease;cis-female;Clinical;combat;Cystic Fibrosis;cystic fibrosis mouse;Cystic Fibrosis Transmembrane Conductance Regulator;cytokine;Data;data registry;Disease;Disparity;epidemiologic data;Estradiol;Estrogen Receptors;Estrogens;Etiology;Event;experience;extracellular;Female;Feminization;Foundations;Gender;gender affirming hormone therapy;gender difference;gender disparity;gender diverse;Genomics;Goals;GPER gene;Health;hormonal contraception;Hormone use;Human;Immunity;improved;Individual;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;Inflammatory Response;Internet;Leukocyte Elastase;Life Expectancy;Lung;Lung Diseases;Lung infections;lung injury;male;Mediating;Microbe;Modeling;mortality;mouse model;Mus;Natural Immunity;Nebulizer;neutrophil;non-genomic;novel therapeutics;Orchiectomy;Outcome;Outcome Study;Outcomes Research;Ovariectomy;Ovulation;pathogen;Pathway interactions;patient registry;Peptide Hydrolases;Peripheral;Persons;Population;Process;Production;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Puberty;Public Health;pulmonary function;pulmonary function decline;Pulmonary Inflammation;Reactive Oxygen Species;Recurrence;recurrent infection;Research;respiratory;Respiratory Disease;respiratory morbidity;Respiratory Signs and Symptoms;Respiratory Tract Infections;response;Sampling;Serine Protease;sex;Sex Differences;sex disparity;Sputum;Stimulus;Structure;Structure of parenchyma of lung;Testing;therapeutic target;transgender;transgender women;treatment strategy;women's outcomes;Work

PROJECT_TITLE: Estrogen-mediated effects on neutrophil function and airway inflammatory response

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-F (50)]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: ANN ARBOR

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: MI

PHR: The number of Veterans living with dementia (VLWD) is expected to increase by 2030 to nearly 340,000; these Veterans and their caregivers often have complex psychosocial and health needs. Coordinating this care is complicated by the fact that most VLWD are Medicare-eligible and therefore use care both through the VA and Medicare, though dual use is often associated with duplication of services and potentially inappropriate care. In light of these complexities, a 2019 VHA directive mandated that VA facilities establish a Dementia System of Care to provide person-centered services for these VLWD. The goals of this project are to examine the links between dual use, continuity of care, and the patient-centered outcome of home time. Then, we will interview staff and VLWD-caregiver dyads at high- and low-performing VA facilities to identify dementia care delivery strategies that maximize home time. Finally, with a Stakeholder & Expert Panel that includes clinicians, researchers, and a VLWD-caregiver dyad, we will identify promising strategies for a dementia care toolkit.

PI_NAMEs: KREIN, SARAH  (contact);MAUST, DONOVAN T

PROJECT_TERMS: Aging;Ambulatory Care;Attention;care coordination;care delivery;care seeking;care systems;Caregivers;caregiving;Caring;Case Manager;Collaborations;Communities;Community Healthcare;Complex;Continuity of Patient Care;cost;Data;Dementia;dementia care;Dementia caregivers;design;Drug Prescriptions;Eligibility Determination;Enrollment;expectation;experience;Family;Goals;Guidelines;Health;Health Services Accessibility;high risk;Home;Hospitalization;improved;indexing;Individual;innovation;insight;interest;Intervention Trial;Interview;Knowledge;Learning;Left;Light;Link;Long-Term Care;Medical center;Medicare;Medicare claim;member;Methodology;Methods;military veteran;older adult;opioid mortality;opioid overdose;Outcome;Outpatients;Patient-Focused Outcomes;Patients;Performance;person centered;Pharmaceutical Preparations;Policies;preference;prescription opioid;primary care practice;primary outcome;programs;Provider;psychosocial;Publishing;Quality of Care;Recording of previous events;research and development;Research Personnel;Research Priority;Services;skills;Source;Structure;System;Systems Development;Time;tool;Variant;Veterans;Visit;Voice;Work

PROJECT_TITLE: Putting the puzzle together: Leveraging dual use to improve care for Veterans living with dementia

STUDY_SECTION_NAME: HSR-6 Aging, Recovery, and Workforce[HSR6]


NIH_SPENDING_CATS: Asthma;Childhood Obesity;Clinical Research;Genetics;Human Genome;Lung;Nutrition;Obesity;Pediatric;Prevention

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Elucidating adipose tissue pathways associated with obesity and asthma in children will improve our understanding of this important phenotype. Furthermore, it may allow us to identify potential therapeutic targets and other ways to improve the management of obese children with asthma.

PI_NAMEs: FORNO, ERICK  (contact)

PROJECT_TERMS: Abbreviations;Acute;adipokines;Adipose tissue;Affect;Anthropometry;Asthma;asthma exacerbation;asthmatic;atopy;Biological Markers;Blood;Body Composition;Body fat;Body mass index;bronchial epithelium;Candidate Disease Gene;Cardiovascular Diseases;Cells;Child;Childhood Asthma;cohort;cost;cytokine;Data;Development;Diabetes Mellitus;Disease;disorder control;DNA Methylation;electric impedance;Epigenetic Process;epigenetic regulation;epigenome-wide association studies;epigenomics;Epithelial Cells;Epithelium;Functional disorder;Gene Expression;Gene Expression Alteration;Genes;genetic variant;genome-wide;Genotype;Goals;Heritability;high risk;Immune;improved;indexing;Inflammatory;innovation;insight;Insulin Resistance;Intra-abdominal;Literature;Measures;Mediator;Morbid Obesity;Morbidity - disease rate;new therapeutic target;Nonpharmacologic Therapy;novel;novel strategies;Obesity;obesity in children;obesity management;obesity-associated asthma;older adult;Outcome;Overweight;overweight child;Pathogenesis;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Phenotype;Process;Production;Proliferating;Public Health;pulmonary function;Quality of life;recruit;Regulation;Research;respiratory smooth muscle;response;Role;Sample Size;secondary outcome;Severities;Severity of illness;Signal Transduction;Smooth Muscle Myocytes;Source;subcutaneous;Testing;therapeutic target;Tissue-Specific Gene Expression;Tissues;Transcript;transcriptome;transcriptome sequencing;transcriptomics;treatment response;Validation;Vulnerable Populations

PROJECT_TITLE: Obesity and Childhood Asthma: The Role of Adipose Tissue

STUDY_SECTION: IRAP

STUDY_SECTION_NAME: Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section[IRAP]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;Hematology;Orphan Drug;Primary Immunodeficiencies;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE The main objective of this proposal is to develop a site-specific gene editing strategy for the treatment of primary immunodeficiency caused by mutations into the tightly regulated RAG1 gene. This disease represents an ideal candidate for the new gene correction strategy because preclinical studies of Hematopoietic Stem Cells (HSC) gene therapy have already shown i) evidence of potential efficacy even with few amounts of functionally corrected cells; ii) critical safety issues due to ectopic and unregulated transgene expression from conventional integrating vectors. Here we will overcome this hurdle by exploiting nuclease mediated homologous recombination to directly fix RAG1 mutations and restore both its function and expression control, thus providing the ultimate solution for the treatment of RAG1 patients and opening new avenues for HSC gene editing based therapies.

PI_NAMEs: GENOVESE, PIETRO  (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Acceleration;Achievement;Address;Adverse effects;Affect;Allogenic;Authorization documentation;Autoimmune;Autoimmunity;Autologous;Automobile Driving;B-Cell Antigen Receptor;B-Cell Development;Bar Codes;base editing;Biological;Biological Assay;Biotechnology;CD34 gene;Cell Cycle Arrest;Cell Cycle Progression;Cell Transplantation;cell type;Cells;Chromosomal translocation;Clinical;clinical development;clinically relevant;Code;Collaborations;Complementary DNA;conditioning;congenital immunodeficiency;CRISPR/Cas technology;curative treatments;Cytotoxic agent;Defect;delivery vehicle;design;Development;Disease;disease phenotype;disease-causing mutation;donor stem cell;Dose;Drug usage;efficacy evaluation;efficacy testing;Electroporation;engineered stem cells;Engineering;Engraftment;Exons;experimental study;gene correction;Gene Delivery;gene repair;gene replacement;gene therapy;gene-editing approach;Genes;Genetic Diseases;Genetic Recombination;Genome Stability;Genomics;genotoxicity;Goals;Hematology;Hematopoietic Stem Cell subsets;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Heterozygote;high risk;homologous recombination;Homologous Transplantation;Human;IL2RG gene;immune reconstitution;immunodeficiency;Immunologics;Immunotoxins;improved;In Vitro;in vivo;innovation;Insertional Mutagenesis;Lentivirus;Lymphocyte;Lymphoid;Lymphoid Cell;Marketing;Mediating;Medical;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Mutate;Mutation;Nature;new technology;novel;nuclease;Omenn syndrome;Opportunistic Infections;Organoids;Output;Patients;Physiological;Positioning Attribute;Pre-Clinical Model;preclinical study;preservation;Procedures;Process;promoter;Proteins;Protocols documentation;PTPRC gene;RAG1 gene;Rag1 Mouse;Reaction;reconstitution;Regimen;repair strategy;Reporting;research clinical testing;response;Risk;Safety;safety and feasibility;screening;Severe Combined Immunodeficiency;single-cell RNA sequencing;Site;Specificity;stem cell gene therapy;stem cell genes;stem cell therapy;T cell differentiation;T-Lymphocyte;Technology;Testing;Therapeutic;therapeutically effective;Thymus Gland;tool;Toxic effect;TP53 gene;transgene expression;translational medicine;Translational Research;Translations;Transplantation;Transplantation Conditioning;treatment strategy;United States National Institutes of Health;V(D)J Recombination;Validation;vector;Viral Vector;Xenograft procedure

PROJECT_TITLE: Development, Optimization and Preclinical Modeling of Hematopoietic Stem Cell Gene Editing for the Treatment of RAG1 Immunodeficiency

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Eye Disease and Disorders of Vision;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: SHERMAN OAKS

ORG_NAME: TRETHERA CORPORATION

PHR: PROJECT NARRATIVE Optic Neuritis (ON) patients need new, effective, and well-tolerated therapies to improve treatment outcomes and reduce side effects, and for these patients, reducing aberrant lymphocyte activation with targeted drugs is a promising therapeutic strategy. Our company, Trethera, is developing a novel small-molecule drug, TRE-515, to treat ON by targeting a pathway required for lymphocyte activation. In the proposed project, we will conduct critical preclinical work to further evaluate the safety of TRE-515 as a drug for ON and to further study how TRE- 515 affects ON relevant cells and disease stages.

PI_NAMEs: SCHULTZ, KENNETH  (contact)

PROGRAM_OFFICER_NAME: LEE, PAEK-GYU

PROJECT_TERMS: Acceleration;Activated Lymphocyte;Acute;Affect;Area Under Curve;Autoantigens;Autoimmune Diseases;autoreactive T cell;Award;B-Cell Activation;B-Lymphocytes;Biological Markers;Blindness;Blood;cell injury;Cells;Clinical;clinical phenotype;Clinical Trials;Clinical Trials Design;Combined Modality Therapy;Consumption;Contrast Sensitivity;Data;Defect;Demyelinations;Deoxycytidine;Deoxycytidine Kinase;Deoxyribonucleosides;Deoxyuridine;Development;Disease;DNA biosynthesis;dosage;Dose;Drug Targeting;Enzymes;Experimental Autoimmune Encephalomyelitis;Eye;Frequencies;genotoxicity;Guidelines;Histologic;Histology;Histopathology;Human;Image;Immune;immune cell infiltrate;Immune system;improved;in vivo;in vivo monitoring;Inflammation;inhibitor;Knock-out;Leucocytic infiltrate;Life;lymph nodes;Lymphocyte;Lymphocyte Activation;lymphocyte proliferation;Measures;Methylprednisolone;Micronucleus Tests;Modeling;mouse model;Multiple Sclerosis;Mus;Myelin;novel;novel therapeutics;nucleoside inhibitor;Optic Nerve;Optic Neuritis;Orphan Drugs;Outcome;Pathogenicity;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phenotype;Plasma;Positron-Emission Tomography;potential biomarker;pre-clinical;preclinical study;Preclinical Testing;Property;Quality of life;radiotracer;Recovery;Regimen;replication stress;response;Retinal Ganglion Cells;Safety;side effect;small molecule;small molecule inhibitor;Spleen;Standard Model;standard of care;Steroids;Study models;success;Symptoms;T-Cell Activation;T-Cell Receptor Genes;T-Lymphocyte;targeted biomarker;Testing;Therapeutic;Therapeutic Effect;Time;Toxic effect;Transgenic Organisms;Treatment outcome;tripolyphosphate;Vision;Visual;Visual Acuity;Work

PROJECT_TITLE: Development of a Novel, Targeted Small Molecule Inhibitor of the Nucleoside Salvage Pathway to Treat Optic Neuritis


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Regenerative Medicine

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: NARRATIVE Transforming Growth Factor (TGF)-Beta superfamily members play a critical role in repair, remodeling and fibrosis of the infarcted heart, signaling through intracellular effectors, the Smads and through non-Smad pathways. The current proposal will investigate cell- specific actions of Smad1 cascades in the infarcted heart. In vivo experiments using cell- specific knockout mice, in vitro loss- and gain-of-function studies and single cell RNAseq experiments will be performed to study Smad1-mediated actions on fibroblasts, macrophages, cardiomyocytes and pericytes, to dissect the molecular mechanisms responsible for Smad1 effects, and to explore the role of TGF-Beta signaling responses in mediating subset-specific functions of immune and reparative cells.

PI_NAMEs: FRANGOGIANNIS, NIKOLAOS G (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Activins;Acute;Affect;angiogenesis;Anti-Inflammatory Agents;Attenuated;Binding;Biological Assay;Blood Vessels;Bone Morphogenetic Proteins;Cardiac;Cardiac Myocytes;cardiac repair;Cells;Characteristics;chemokine;Cicatrix;Complex;Cytokine Activation;Data;Development;Differentiation and Growth;Down-Regulation;Endothelial Cells;Event;experimental study;Family;Fibroblasts;Fibrosis;Flow Cytometry;Follistatin;Functional disorder;gain of function;Geometry;Growth Factor;healing;Heart failure;Heterogeneity;Hypertrophy;Immune;immune function;In Vitro;in vitro Assay;in vivo;Infarction;Inflammation;Inflammatory Response;insight;Integrins;interstitial;Ischemia;Knockout Mice;Ligand Binding;loss of function;Macrophage;Mediating;member;Molecular;morphogens;mortality;Myeloid Cells;Myocardial;Myocardial Infarction;Myocardium;Myofibroblast;Pathway interactions;Patients;Pericytes;Phagocytes;pharmacologic;Phenotype;Play;Property;Protein Isoforms;Proteomics;Reactive Oxygen Species;receptor;recruit;Regulation;repair function;repaired;Reperfusion Therapy;Resolution;response;restraint;Role;Signal Transduction;single nucleus RNA-sequencing;single-cell RNA sequencing;STAT6 gene;Stromal Cell-Derived Factor 1;Testing;TGF-beta type I receptor;TGFB1 gene;TGFBR2 gene;Time;TP53 gene;transcriptome sequencing;transcriptomics;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;transforming growth factor beta3

PROJECT_TITLE: Resolution of inflammation in healing myocardial infarcts

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;HIV/AIDS;Infectious Diseases;Mental Health;Pediatric;Pediatric - AIDS;Prevention;Women's Health Research

ORG_CITY: BALTIMORE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative This implementation science grant aims to understand PrEP user choices, preferences and implementation impact of the roll-out of long-acting injectable (LAI) PrEP alongside oral PrEP among women in Malawi. The design will: (1) evaluate longitudinal patterns of oral and long-acting injectable PrEP use in women in Malawi and the impact of tracing on re-engagement in PrEP care; (2) assess decision-making among injectable and oral PrEP users and providers, as well as preferences for implementation delivery and support; and (3) synthesize evidence and local inputs to design strategies for optimizing PrEP continuation and re-engagement to achieve implementation impact for women in Malawi. Findings will provide clarity around PrEP users patterns and outcomes of PrEP implementation and support the development of PrEP engagement interventions co-designed with the Community Partnership Council (CPC), Ministry of Health, implementing partners, providers, and PrEP users.

PI_NAMEs: NYONDO-MIPANDO, ALINANE LINDA;SCHWARTZ, SHEREE RENAE (contact)

PROJECT_TERMS: Acceleration;Africa;Africa South of the Sahara;Appointment;Back;Behavioral;Biomedical Technology;Blood drug level result;Caring;cis-female;Client;Clinic;Clinical;Communication;Communities;community partnership;community transmission;comparative;Dapivirine;Data;Decision Making;design;Development;Drug resistance;Educational workshop;Effectiveness;efficacy trial;experimental study;follow-up;Funding;Goals;Grant;Health;Health Personnel;Heterogeneity;high risk;HIV;HIV risk;human centered design;implementation outcomes;implementation science;implementation strategy;Individual;Injectable;Interruption;Intervention;Interview;Malawi;mathematical model;Modeling;network models;novel;optimism;Oral;Outcome;Participant;Patients;Pattern;Persons;Phase;pre-exposure prophylaxis;preference;Prevention;Provider;provider communication;Risk;Sampling;scale up;Series;Services;Site;South Africa;Tail;Telephone;Testing;Theoretical Domains framework;Therapeutic;transgender women;transmission process;Woman;Work;Zambia

PROJECT_TITLE: Better Info on Women's PrEP Choices and Outcomes in Malawi


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Cardiovascular disease accounts for 1 in every 3 deaths in the US, many of which are caused by pathological cardiac hypertrophy and subsequent heart failure, for which there is no cure. Our proposed studies aim to decipher the molecular mechanisms contributing to pathological cardiac hypertrophy. We anticipate that this knowledge will help to develop new, mechanistically specific and selective treatments for pathological cardiac hypertrophy and, thus, reduce mortality from this form of heart disease.

PI_NAMEs: GLEMBOTSKI, CHRIS  (contact)

PROJECT_TERMS: absorption;Address;Aldosterone;Amino Acids;Binding;Binding Proteins;Calcium;cancer cell;Cancer Cell Growth;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Catalytic Domain;cell type;Cessation of life;Data;Ectopic Expression;Endoplasmic Reticulum;endoplasmic reticulum stress;Ensure;Epithelial Cells;Glucocorticoids;Growth;Heart;Heart Diseases;Heart failure;heart function;Heart Hypertrophy;Human;Hypertrophy;innovation;Interruption;Kidney;knock-down;Knowledge;Left;Leucine Zippers;Link;Mediating;Membrane;Methods;misfolded protein;Molecular;mortality;multicatalytic endopeptidase complex;Mus;Muscle Cells;Neonatal;novel;overexpression;Pathologic;Pathology;Peptides;Phosphotransferases;Physiologic intraventricular pressure;Plasma;pressure;Protein Biosynthesis;protein folding;Protein Overexpression;Protein Secretion;Proteins;Proteome;proteostasis;Rattus;receptor;renal epithelium;response;Role;Serum;Serum Proteins;Sgk protein;Side;Signal Transduction;Site;Study of serum;System;Therapeutic;ubiquitin-protein ligase;Ventricular

PROJECT_TITLE: Non-canonical ERAD as a Regulator of Cardiac Hypertrophy

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Conditions Affecting the Embryonic and Fetal Periods;Diabetes;Fetal Alcohol Spectrum Disorders (FASD);Intellectual and Developmental Disabilities (IDD);Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Substance Misuse;Substance Misuse Prevention

ORG_CITY: CHAPEL HILL

ORG_DEPT: NUTRITION

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE Prenatal alcohol exposure (PAE) causes growth deficits in the offspring; these deficits predict the severity of the accompanying behavioral deficits, and mechanism underlying this impaired growth is unclear. Using a mouse model of FASD, this proposal tests the hypothesis that these growth deficits are driven, in part, by alcohol-mediated disruptions in maternal insulin sensitivity and signaling and reduced fetal access to glucose. An understanding of how alcohol disrupts maternal-fetal energy metabolism will inform the development of nutrition-based therapies that may improve PAE outcomes.

PI_NAMEs: SAINI, NIPUN  (contact)

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: Address;Affect;Alcohol consumption;alcohol effect;alcohol exposure;alcohol intervention;alcohol prevention;alcohol testing;Alcohols;Amino Acids;Animals;Area;at-risk pregnancies;Behavior assessment;Behavioral;behavioral impairment;Biological Assay;Brain;Catabolism;Clinical;clinically relevant;Cognitive deficits;cognitive function;Data;Development;disability;Dysmorphology;Embryo;Energy Metabolism;Energy-Generating Resources;Face;Failure;fasting glucose;Fatty Acids;fetal;Fetal Alcohol Exposure;Fetal Alcohol Spectrum Disorder;Fetal Development;Fetal Growth;Fetal Growth Retardation;Fetal Liver;Fetal Reduction;Fetal Weight;Fetus;Fingerprint;Functional disorder;Future;Genetic;Gluconeogenesis;Glucose;glucose metabolism;Glucose tolerance test;Glycogen;Goals;Growth;Hepatic;Hormones;Hypoglycemia;Impaired cognition;Impairment;improved;insight;Insulin;Insulin Resistance;insulin sensitivity;insulin signaling;Intervention;Knockout Mice;Knowledge;Lead;lead candidate;Leptin;leptin receptor;Leptin resistance;Liver;liver metabolism;loss of function;Mediating;Metabolic;metabolic abnormality assessment;metabolic profile;Metabolism;Methodology;Methods;Modeling;Modification;mouse model;Mus;neglect;neurobehavioral;Neurodevelopmental Deficit;novel;Nutrient;nutrition;offspring;Organ;Outcome;oxidation;Phase;Placental Lactogen;Plasma;Pregnancy;pregnant;Pregnant Women;programs;Prolactin;Public Health;Research;response;Risk Factors;Severities;Signal Transduction;Skeletal Muscle;skills;Testing;Tracer;Training;Transgenic Organisms;Triglycerides;Urea;Weight;Work

PROJECT_TITLE: Maternal Fetal Metabolic Disruption in Prenatal Alcohol Exposure

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Genetics

ORG_DEPT: DENTISTRY

PHR: Identification and characterization of new mechanisms of how the cell responds to DNA damage will significantly impact our understanding of cancer etiology and treatment. The project will reveal novel inter- organelle crosstalk between cytoskeleton factors and DNA damage repair, and thereby, significantly improving our understanding of cancer progression and treatment.

PI_NAMEs: PENG, AIMIN  (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Acetylation;ataxia telangiectasia mutated protein;ATM activation;ATP Hydrolysis;Autophagocytosis;Binding;Biochemical;Biology;Cancer Etiology;cancer therapy;Cell Death Induction;Cell Proliferation;Cell Survival;Cells;Chromatin;chromatin remodeling;Chromatin Remodeling Factor;Chromatin Structure;Clinical;Communication;Complex;condensin;Cytoplasm;Cytoplasmic Structures;Cytoskeleton;Data;Development;DNA;DNA Damage;DNA Double Strand Break;DNA Repair;Double Strand Break Repair;Ensure;Etiology;Event;Exhibits;Family;Genome;genome integrity;Genome Stability;Goals;HDAC1 gene;histone methylation;Homeostasis;Human;human disease;Hypersensitivity;improved;In Vitro;in vivo;innovation;insight;Kinesin;Kinetochores;knock-down;Knock-out;Knowledge;Laboratories;Maintenance Therapy;Malignant Neoplasms;Mediating;member;Microtubule Depolymerization;Microtubule Stabilization;Microtubules;Mitotic;Mobility decline;Modeling;Motor;Movement;mutant;Nonhomologous DNA End Joining;novel;Nuclear;Organelles;Perception;pharmacologic;Phosphorylation;Physical condensation;Play;Poison;Protein Array;protein complex;protein function;protein transport;Proteins;Radiation;recruit;Regimen;Regulation;Relaxation;repaired;Repairosome liposome;response;Role;segregation;Signal Transduction;Site;Therapeutic;therapy outcome;tool;Toxic effect;Tubulin;tumor progression;Vesicle

PROJECT_TITLE: The novel role of microtubule regulators in the DNA damage response

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


NIH_SPENDING_CATS: Adolescent Sexual Activity;Behavioral and Social Science;Dissemination and Implementation Research;HIV/AIDS;Infectious Diseases;Mental Health;Pediatric;Prevention;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research;Youth Violence

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Intimate partner violence (IPV) is an important contributor to the HIV epidemic among women globally, and identifying and responding to women in generalized HIV epidemic settings who experience IPV is an important HIV prevention strategy. Given the high burden of both IPV and incident HIV among AGYW in South Africa, biomedical HIV prevention options that do not require participation from both partners, such as HIV antiretroviral pre-exposure prophylaxis (PrEP), are critical. This research aims to guide the implementation of approved PrEP modalities among IPV-exposed AGYW in South Africa, which will have important implications for biomedical HIV prevention implementation among priority populations globally.

PI_NAMEs: BEKKER, LINDA-GAIL GAIL;GIOVENCO, DANIELLE  (contact)

PROJECT_TERMS: Address;Adherence;Adolescent;Advocate;Affect;aged;AIDS prevention;Anti-Retroviral Agents;Awareness;Caring;Child;Communities;community advisory board;Consultations;Cross-Sectional Studies;Dapivirine;Development;Disclosure;Education;effectiveness/implementation trial;Epidemic;Equity;evidence base;experience;Exploration, Preparation, Implementation, and Sustainment;Exposure to;Face;Female Adolescents;financial incentive;Forcible intercourse;Future;health belief;Health Personnel;HIV;HIV anti-retroviral;HIV Infections;HIV risk;implementation strategy;improved;Incidence;Individual;infancy;informant;Injectable;innovation;Interview;intimate partner violence;Knowledge;Link;male;meetings;member;Mental Health;Modality;Modeling;novel;novel strategies;Oral;Outcome;Participant;Pathway interactions;peer;Persons;pilot trial;Play;Policy Maker;Population;pre-exposure prophylaxis;preference;prevent;Prevention;Prevention strategy;programs;psychologic;Public Health;Regimen;Reporting;Research;resilience;Resources;Risk;risk minimization;Role;service providers;Services;Sexual Health;social stigma;South Africa;South African;Spouses;Suggestion;Surveys;System;Testing;Training;Trauma;uptake;Violence;violence exposure;Woman;Work;young woman

PROJECT_TITLE: Meeting South African adolescent girls and young women who experience intimate partner violence where they are: Developing an implementation strategy for linkage to PrEP options


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Mental Health;Mental Illness;Pediatric;Suicide

ORG_CITY: PISCATAWAY

ORG_DEPT: PSYCHOLOGY

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Suicide risk is increasing in preteens, 8-12 years old: in clinical samples (e.g., inpatient psychiatry), more than 40% have seriously considered suicide and nearly 20% have attempted suicide. Our knowledge of suicide risk has been limited by the paucity of developmentally appropriate tools to assess suicidal thoughts, and relevant risk factors, in preteens. The goal of this study is to adapt a developmentally and culturally appropriate measures of suicide risk for preteens (via community-engaged research) and to examine different phenotypes (i.e., presentations) of suicide risk among 150 at-risk preteens following discharge from acute psychiatric care settings.

PI_NAMEs: GLENN, CATHERINE ROSE;KLEIMAN, EVAN  (contact);LIU, RICHARD T

PROGRAM_OFFICER_NAME: MURPHY, ERIC ROUSSEAU

PROJECT_TERMS: 12 year old;18 year old;Acute;Address;Adolescent;Adult;Affect;Age;age group;Biosensor;Caregivers;children of color;Clinical;clinical risk;cognitive interview;Communities;community engaged research;Complement;Death Rate;design;Development;diaries;Emotional;Event;evidence base;experience;externalizing behavior;Feedback;Feeling suicidal;follow-up;Funding;Future;General Hospitals;Goals;Grant;high risk;high risk population;hospital readmission;Hospitalization;informant;Inpatients;Interview;Knowledge;Life;life span;Massachusetts;Measures;modifiable risk;Monitor;National Institute of Mental Health;non-suicidal self injury;Outcome;Patient Self-Report;Phenotype;Population;preadolescence;Prevalence;primary caregiver;Process;Protocols documentation;Psychiatric therapeutic procedure;Psychiatry;real time monitoring;recruit;Research;Risk;Risk Factors;risk prediction;Sampling;Site;Sleep Disorders;Sleep disturbances;Social Environment;social stress;suicidal;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Teenagers;Time;tool;translational potential;Universities;Validation;Work;Wrist;Youth

PROJECT_TITLE: Clarifying phenotypes of suicide risk in preteen youth: An intensive longitudinal assessment study

STUDY_SECTION_NAME: Special Emphasis Panel[ZMH1 ERB-E (05)]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Dental, Oral, and Craniofacial Disease;Machine Learning and Artificial Intelligence

ORG_CITY: CAMBRIDGE

ORG_NAME: ADA FORSYTH INSTITUTE, INC.

PHR: Narrative: This project aims to develop a streamlined platform for the fast development of an innovative system of bioactive dental restoratives that is characterized by its self-healing and dynamic capabilities that may be tailored to individual patient needs. Employing hybrid modeling and simulation approaches, we will refine the formulation and guide the precise placement of restorative materials for effective caries treatment.

PI_NAMEs: BIDLACK, FELICITAS B;MIRMOMEN, LEYLA ;SUN, JIRUN  (contact);ZHANG, YULONG

PROGRAM_OFFICER_NAME: LOPEZ, ORLANDO

PROJECT_TERMS: Acceleration;Acids;Address;Adhesions;Adhesives;Aging;anti-microbial drug;antimicrobial;Artificial Intelligence;Binding;Biocompatible Materials;Biological;bisphosphonate;Black race;Ceramics;chemical bond;chemical property;chemical reaction;Chemistry;Classification;Clinical;Clinical effectiveness;clinically relevant;Composite Resins;Computer Models;cost;Cues;Data;Dental;dental adhesive;dental biofilm;Dental Care;Dental caries;Dental Enamel;Dental Materials;Dental Research;Dentin;Dentistry;design;Development;digital;Engineering;Ensure;Environment;Equipment;Esthetics;Evaluation;Fatigue;Filler;Formulation;Generations;Geometry;Goals;Growth;healing;Human;Hybrids;improved;Individual;individual patient;innovation;Laboratories;Learning;Life;Location;Machine Learning;manufacture;materials science;mechanical properties;Mechanics;Microbial Biofilms;mineralization;Minerals;Mission;Modeling;models and simulation;nano;novel;novel strategies;Odontogenesis;Oral;Patients;Performance;photocuring;physical property;Physics;Plant Resins;Precision therapeutics;prevent;Procedures;Process;Property;Publications;Publishing;remineralization;repaired;Research;response;restorative dentistry;restorative material;Route;Salivary;Secure;Series;Signal Transduction;simulation;Stimulus;success;System;Techniques;Testing;Tooth structure;tooth surface;Twin Multiple Birth;user-friendly;Validation;virtual;virtual laboratory;virtual library;Vision;zirconium oxide

PROJECT_TITLE: Virtual Twin-Powered Rapid Development of Bioactive Multifunctional Dental Restoratives

STUDY_SECTION_NAME: Special Emphasis Panel[ZDE1 CC (14)]


NIH_SPENDING_CATS: Biotechnology;Genetics;Immunotherapy;Infectious Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CHICAGO

ORG_DEPT: PATHOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Narrative Successful control of chronic viruses and cancer greatly depends on vigorous CD8 T cell response without losing function. This study aims to rapidly identify novel genetic mechanisms that can be used to overcome T cell exhaustion and recover T cell function through cutting-edge technologies.

PI_NAMEs: CUI, WEIGUO  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Adoptive Transfer;Algorithms;Animal Model;Antigens;antiviral immunity;Biological Process;candidate selection;CD8-Positive T-Lymphocytes;Cell Count;Cell Physiology;Cell Therapy;Cells;Chronic;chronic infection;Clustered Regularly Interspaced Short Palindromic Repeats;Communicable Diseases;cost effective;CRISPR screen;CRISPR/Cas technology;design;Epigenetic Process;exhaust;exhaustion;expression vector;gain of function;Gene Deletion;Genes;Genetic;Genetic Transcription;Guide RNA;Harvest;Heterogeneity;high throughput screening;improved;in vivo;Individual;Infection;insight;interest;interleukin-21;Knowledge;Libraries;loss of function;Lymphocytic choriomeningitis virus;Malignant Neoplasms;Mediating;Methods;Modeling;Molecular;Mus;novel;NR4A2 gene;pathogen;Pathway interactions;Phenotype;Population;Production;progenitor;programs;Regulon;Research;Resources;Retroviral Vector;Role;RUNX3 gene;screening;single cell sequencing;single-cell RNA sequencing;stem cells;T cell differentiation;T cell regulation;T cell response;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Therapeutic;transcription factor;Transcriptional Regulation;Transgenic Organisms;Tryptophanase;Tumor Immunity;Validation;Viral;Viral Cancer;Virus;Virus Diseases;Work

PROJECT_TITLE: High-throughput discovery of novel transcriptional programs regulating T cell exhaustion

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


ORG_DEPT: PHARMACOLOGY

PHR: While emerging evidence supports the role of astrocytes in the pathogenesis of Parkinson’s disease (PD), the mechanistic details remain largely unknown. LRRK2 kinase is a promising therapeutic target in PD previously linked with astrocyte dysfunctions. This proposal will explore the novel hypothesis that LRRK2 directs signaling pathways in astrocytes that contribute to PD pathogenesis and, by doing so, will facilitate effective therapies to prevent and treat PD.

PI_NAMEs: PARISIADOU, LOUKIA  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Agonist;Animals;Applications Grants;Astrocytes;astrogliosis;Autopsy;Axon;Behavior;Biochemical;Biological Markers;Brain;cell type;Clinical;Clinical Trials;clinically relevant;Code;comparison control;Corpus striatum structure;Data;Disease;disease model;Disease Progression;Dopamine;Dopamine D2 Receptor;dopaminergic neuron;effective therapy;Etiology;Event;Exhibits;experimental study;Functional disorder;Future;Genetic;Genetic Models;Goals;Hyperactivity;Impairment;in vivo;Inflammasome;Inflammation;Inflammatory;inflammatory marker;inflammatory milieu;Inflammatory Response;inhibitor;innovation;insight;interest;Intervention;Investigation;kinase inhibitor;Knock-in Mouse;Knock-out;Light;Link;LRRK2 gene;Mediating;Modeling;Molecular;Mus;Mutation;mutation carrier;Nerve Degeneration;neuroinflammation;neuron loss;neuroprotection;neurotoxic;neurotoxicity;novel;Output;Parkinson Disease;Parkinsonian Disorders;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;permissiveness;pharmacologic;Phase III Clinical Trials;Phenotype;Phosphotransferases;Population;pre-clinical;prevent;Process;Protein Kinase;putamen;receptor;Receptor Signaling;receptor-mediated signaling;Regulation;research clinical testing;Risk;Role;Signal Pathway;Signal Transduction;small molecule;small molecule inhibitor;Specificity;sporadic Parkinson's Disease;Stimulus;Synapses;System;Testing;therapeutic target;Thinking;trafficking;transmission process;Untranslated RNA;Variant;Viral;Work

PROJECT_TITLE: The Role of Striatal Astrocytic Dopamine D2 Receptor Signaling in the Pathogenesis of LRRK2-Mediated Parkinson's Disease

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


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative We have identified proteins that transfer cholesterol between different membranes in cells. We will define molecular mechanisms whereby these proteins act, including identifying novel proteins with which they cooperate to accomplish cholesterol movement. These studies are expected to provide fundamental insight into pathways regulating cholesterol homeostasis and may suggest opportunities for modulating lipid levels and metabolism.

PI_NAMEs: TONTONOZ, PETER J (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Affect;Animal Model;Biological;Biology;Blood Vessels;Cardiovascular Diseases;Cell Culture System;Cell Culture Techniques;Cell membrane;Cell Physiology;cell type;Cells;Chemicals;Chimeric Proteins;Cholesterol;cholesterol absorption;Cholesterol Homeostasis;cholesterol-binding protein;Collaborations;CRISPR/Cas technology;Cultured Cells;Data;Dietary Cholesterol;Disease;Engineering;Esterification;Etiology;Family;Future;Gene Modified;Homeostasis;in vivo;Inflammation;Inflammatory Response;insight;Knowledge;Label;Link;lipid metabolism;lipid transport;Lipids;LoxP-flanked allele;Mammalian Cell;Membrane;Metabolic;Metabolic Diseases;Metabolism;Methods;Modification;Molecular;Movement;Mus;Mutagenesis;mutant;novel;Pathology;Pathway interactions;Phosphorylation;Phosphotransferases;Physiological;Physiology;Play;Post-Translational Protein Processing;Proteins;Regulation;response;reverse cholesterol transport;Role;Second Messenger Systems;Series;Site;SNAP23 gene;Sphingomyelins;SRE-2 binding protein;Steroid biosynthesis;Sterol O-Acyltransferase;Testing;Therapeutic Intervention;Work

PROJECT_TITLE: Mechanisms of nonvesicular cholesterol transport

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Pediatric;Pediatric - AIDS;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Project Narrative Black women are disproportionately impacted by HIV accounting, for 54% of new infections while constituting only 13% of women in the US in 2019, yet limited interventions are available to optimize PrEP uptake and persistence among this population. In the South, historical racism, gender-based discrimination, and the absence of integrated family planning and prevention-oriented sexual healthcare combine to contribute to low PrEP use Black women. This study aims to address this by developing and pilot testing the telehealth intervention EMPOWER (Enhancing and Motivating PrEP Options among Women through Empowerment and Resilience).

PI_NAMEs: BROWN, MONIQUE JANIEL;HAIDER, MOHAMMAD RIFAT  (contact)

PROJECT_TERMS: acceptability and feasibility;Accounting;Address;African American Women;AIDS prevention;Awareness;Behavior;black women;Blood;classism;Clinical;Cognitive Therapy;comparison intervention;Complex;cost;Crossover Design;Decision Making;Deep South;Development;Diphosphates;Discrimination;Disparity;Disproportionately impacts women;dosage;Dose;Dryness;Education;Elements;Eligibility Determination;Emotions;empowerment;emtricitabine;Family Planning;Formulation;Fumarates;Gender;Grant;group intervention;Health Insurance;Health Personnel;Healthcare;Heterosexuals;high risk;High Risk Woman;HIV;holistic approach;improved;Individual;Infection;Injectable;Institutional Racism;Insurance Coverage;Intervention;intervention refinement;Interview;Marketing;Measures;Medicaid;Medical;medication compliance;men;microaggression;mindfulness;minority stress;Modeling;Newly Diagnosed;Oral;Outcome;perceived discrimination;Perception;Personal Satisfaction;pilot test;pilot trial;Play;Population;post intervention;pre-exposure prophylaxis;preference;Prevention;Preventive measure;Procedures;promote resilience;psychosocial;Race;racism;Randomized;Randomized, Controlled Trials;Research;resilience;Risk;Role;sex;Sex Orientation;Sexism;Sexual Health;sexually active;side effect;Site;social norm;social stigma;social structure;South Carolina;Spottings;standard of care;Stereotyping;Supervision;telehealth;Tenofovir;theories;Training;transmission process;uptake;usability;Waiting Lists;Woman

PROJECT_TITLE: Optimizing PrEP uptake for African American women in the South by empowering women to make informed HIV prevention and sexual health choices


NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Orphan Drug;Rare Diseases

PHR: The project will characterize new mechanisms of how the oral cancer cell responds to replication stress and DNA damage, and thereby significantly impacting our understanding of oral cancer progression and drug resistance.

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: ATM activation;Back;Biochemical;biological adaptation to stress;Biology;cancer cell;cancer drug resistance;cancer therapy;cancer type;Cell Cycle;Cell Proliferation;Cells;Chemicals;chemoradiation;chemotherapeutic agent;chemotherapy;Cisplatin;Clinical;clinical development;Collaborations;college;cytotoxicity;Data;Databases;Dentistry;Development;Diagnosis;Distant Metastasis;DNA biosynthesis;DNA Damage;DNA replication fork;Drug resistance;Drug Sensitization;Drug Targeting;effective therapy;Event;Fluorouracil;Goals;Head and neck structure;Hour;HPV negative;hydroxyurea;improved;in vivo;inhibitor;insight;Investigation;Laboratories;Ligase;Malignant Epithelial Cell;malignant mouth neoplasm;Malignant Neoplasms;Mediating;Mitosis;Modeling;Mouth Neoplasms;mouth squamous cell carcinoma;Mus;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel therapeutics;Oncologist;Operative Surgical Procedures;Oropharyngeal;Pathologist;Pathway interactions;Patients;Pharmaceutical Preparations;Pharyngeal structure;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Physiological;Poly(ADP-ribose) Polymerase Inhibitor;Process;Prognosis;Protein Phosphatase 2A Regulatory Subunit PR53;Proteins;Proteolysis;Proteomics;Publishing;Radiation;Recovery;recruit;Recurrent tumor;Regimen;Regulation;repaired;replication factor A;replication stress;Residual Neoplasm;Resistance;response;Role;Signal Transduction;small molecule inhibitor;spatiotemporal;Squamous cell carcinoma;targeted cancer therapy;Therapeutic;therapeutic target;therapy resistant;Time;tumor;tumor progression;tumor xenograft;Ubiquitination;United States;Up-Regulation

PROJECT_TITLE: Greatwall in replication stress/DNA damage responses and oral cancer resistance

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Mental Health;Mental Illness;Neurosciences;Pediatric

ORG_CITY: PULLMAN

ORG_NAME: WASHINGTON STATE UNIVERSITY

ORG_STATE: WA

PHR: PROPOSED SUPPLEMENT PROJECT The proposed study addresses an important shortcoming of the parent project and a critical gap in research, examining frontal asymmetry development, operationalized as a system of reciprocal effects between left and right frontal activation across infancy20, in prediction of risk for disruptive behavior21. The contribution of conver- gence with behavioral development (i.e., approach growth corresponding with shifts towards relative left frontal activation) will be considered, along with infant emerging regulation and maternal sensitivity as moderators22,23. While the parent study provides a comprehensive examination of risk for anxiety and related internalizing symptoms, it does not address disruptive/externalizing outcomes. Yet factors considered as antecedents of anxiety symptoms are also relevant to the development of disruptive symptoms, and it may be that a trajectory of neurophysiological changes protective with respect to anxiety/internalizing symptoms accentuates external- izing symptoms, possibly depending on the inputs from regulatory capacity and caregiving. The proposed pro- ject provides an opportunity to leverage extensive infancy neurophysiological and behavioral assessments conducted in the context of the parent investigation to answer critical research questions concerning disruptive behavior problems, significantly extending the impact of obtained results. It is hypothesized that the pattern of reciprocal brain activity effects wherein dominant left frontal acti- vation (associated with approach/reward orientation) will translate into greater risk for disruptive symptoms. Specifically, we anticipate that (1) dominance of left hemisphere change effects on right activation growth across infancy will confer risk; (2) this risk will be accentuated by slower advances in child regulatory capacity and attenuated by higher maternal sensitivity across infancy. We plan to test these primary hypotheses and attain the objective of this application by pursuing two specific aims:  Aim 1. Modeling frontal EEG changes as predictors as of emerging disruptive symptoms/disorders. Bimonthly assessments of infant EEG, temperament and maternal sensitivity from 6 to 18 months will be con- sidered in predicting previously omitted disruptive symptoms and disorders (e.g., Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder). Assessments begin at 2 months of age measuring covariates: infant birth/medical (e.g., gestational age/weight, APGAR score), family demographic factors, and maternal depres- sion/anxiety. Infant EEG asymmetry markers (i.e., frontal alpha power values), temperament, and maternal sensitivity are evaluated bimonthly starting at 6 months. Laboratory observations provide measures of maternal sensitivity with parent-report used to assess infant temperament, specifically regulatory capacity. Mothers with infants (n=300) recruited at three sites: Pullman, WA, Blacksburg, VA, and Jupiter, FL in the context of the par- ent R01 funded investigation will be asked to contribute data to the proposed study. Specifically, all 300 care- givers will participate in clinical interviews, this time to ascertain severity of externalizing/disruptive problems, also providing responses to related questionnaires. Children will be followed, conducting semi-structured clini- cal interviews with mothers addressing disruptive starting at 24 months. It is hypothesized that greater base- line left frontal activation and stronger left frontal EEG effects across infancy (i.e., left hemisphere dy- namic effects driving change in right activation) would contribute to more severe/frequent disruptive behaviors and increased risk for symptoms/disorders8,24.  Aim 2. Moderation by temperament and caregiving: Child regulatory capacity and maternal sensitivity. We will determine moderating effects of child regulatory capacity and maternal sensitivity on links between EEG markers and disruptive symptoms/disorders. Sensitive caregiving is examined in the parent project and the proposed study provides an opportunity to discover if protective mechanisms are similar for externalizing and internalizing symptoms. Child self-regulation was not considered as a moderator in the parent investiga- tion, yet has been widely demonstrated as protective25,26 and will be examined herein with respect to disruptive problems. Latent changes in child EEG – dominant left hemisphere effects on right frontal activation are expected to confer risk with respect to disruptive behaviors, accentuated by slower advances in atten- tion-based regulation from 6 to 18 months and attenuated by higher levels of maternal sensitivity. Be- cause maternal sensitivity is assessed every two months, we will be able to identify specific develop- mental periods associated with reliable protective effects. This dynamic approach pioneered in the parent study will now be aimed at elucidating risk vs. protection with respect to early disruptive problems and is ex- pected to transform etiology-oriented research in developmental psychopathology. This study will clarify the role of changes in neurophysiology in the emergence of disruptive symptoms8,27, informing preventative efforts by providing potential therapeutic targets. The proposed study will provide currently lacking information related to accentuated risk for disruptive symptoms/disorders as a function of infant neurophysiology and tempera- ment, which can be applied in screening efforts, with malleable periods identified. Importantly, this study prom- ises to specify periods wherein maternal sensitivity can be modified to provide increased protection with re- spect to disruptive behaviors26,28. Identifying these markers is expected to translate into low-cost preventive approaches, in lieu of more intensive services later in childhood29.

PI_NAMEs: BELL, MARTHA ANN ;GARTSTEIN, MARIA A. (contact);JONES, NANCY AARON

PROGRAM_OFFICER_NAME: THOMAS, LAURA ANDERSON

PROJECT_TERMS: Acceleration;Address;Age Months;Anxiety;Anxiety Disorders;anxiety symptoms;anxious behavior;Apgar Score;Attention;Attention deficit hyperactivity disorder;Attenuated;Automobile Driving;Behavior;Behavior assessment;behavior observation;Behavioral;Behavioral inhibition;Behavioral Model;Birth;Brain;caregiving;Caring;Cerebral Dominance;Child;Childhood;Clinical;Communities;cost;Coupling;Data;Data Collection;Demographic Factors;design;Development;Disease;Electroencephalography;Electrophysiology (science);Enrollment;ethnic diversity;Etiology;Evaluation;Family Demographies;Fright;Funding;Gestational Age;Growth;infancy;Infant;infant temperament;Informal Social Control;Interview;Investigation;Jupiter;Laboratories;Left;Life;life span;Link;longitudinal design;maternal depression;Measures;Medical;Methods;Modeling;Mothers;Negative Valence;neurophysiology;Oppositional Defiant Disorder;Outcome;parent project;parenting intervention;Parents;Pattern;Preventive;Problem behavior;protective effect;Psychopathology;Psychophysiology;Questionnaires;Race;recruit;Regulation;Reporting;Research;Research Domain Criteria;response;Rewards;Risk;risk prediction;Role;Sampling;screening;Services;Severities;Shapes;Site;Specific qualifier value;Structure;Symptoms;System;Temperament;Testing;therapeutic target;Time;Translating;transmission process;Weight

PROJECT_TITLE: Precursors of Anxiety: The Role of Lateralized Brain Activation and Maternal Sensitivity

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


NIH_SPENDING_CATS: Aging;Cardiovascular;Heart Disease;Nutrition;Physical Activity;Women's Health Research

ORG_CITY: DURHAM

ORG_DEPT: ORTHOPEDICS

ORG_NAME: DUKE UNIVERSITY

PHR: Project Narrative Heart failure with preserved ejection fraction (HFpEF) affects millions of people, especially older individuals and postmenopausal women. Cardiac and limb muscle abnormalities are a significant problem in HFpEF patients because it contributes to morbidity and mortality. Our goal is to test whether a compound with antioxidant properties restores exercise tolerance and cardiac and limb muscle function in a rodent model of HFpEF relevant for postmenopausal women.

PI_NAMEs: FERREIRA, LEONARDO  (contact)

PROGRAM_OFFICER_NAME: GAO, HONGWEI

PROJECT_TERMS: Accounting;Adult;Affect;Angiotensin II;Animals;Antioxidants;biophysical properties;Biopsy;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cardiovascular system;Clinical;Clinical Trials;comorbidity;Complex;Consumption;Cultured Cells;cytokine;Cytosol;Data;Degenerative polyarthritis;Development;Diabetes Mellitus;Diet;Disease;Disease Marker;Disease Progression;Echocardiography;EFRAC;Elderly;Electron Transport;Enzymes;exercise intolerance;Exercise Tolerance;experimental study;Fatigue;Fatty acid glycerol esters;fluidity;Functional disorder;Glutathione;Goals;Heart failure;Hepatocyte;high reward;high risk;Human;human data;Hypertension;hypertensive;Impairment;improved;In Vitro;in vivo;Inbred WKY Rats;Insulin Resistance;Isometric Exercise;Kidney;kidney dysfunction;Lead;Left;Life;Limb structure;Liquid substance;Liver;Liver diseases;male;Measures;Membrane;Membrane Fluidity;Mental disorders;Metabolic;Metabolism;Mitochondria;mitochondrial dysfunction;Mitochondrial Matrix;Modeling;Morbidity - disease rate;Morphology;mortality;Muscle;Muscle Cells;Muscle function;Muscle Mitochondria;Muscle Weakness;Myopathy;normotensive;novel strategies;Nutrient;Obesity;OGTT;older patient;Older Population;older women;Organ;Ovariectomy;Oxidative Stress;Palmitates;patient subsets;Patients;Persons;Pharmacotherapy;Phenotype;Pilot Projects;Plasma;Postmenopause;Pre-Clinical Model;preclinical study;preservation;prevent;Property;Publishing;Randomized;Rattus;Reactive Oxygen Species;Relaxation;Resistance;Respiration;Rodent;Rodent Model;Running;S-Adenosylhomocysteine;S-Adenosylmethionine;Severity of illness;Skeletal Muscle;Source;stem;sugar;Symptoms;Testing;Thinness;Translating;Translations;United States;uptake;Ventricular;VO2max;Woman

PROJECT_TITLE: Systemic antioxidant treatment for cardiomyopathy, muscle weakness, and exercise intolerance in postmenopausal HFpEF

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TDPS-R(01)]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Dissemination and Implementation Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Pediatric;Pediatric - AIDS;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE Public Health Significance: This study will address an important scientific gap by improving our understanding of the potential impact of strategies for relinkage to care for Black sexual minority men with HIV. This proposal addresses the NIH Office of AIDS Research Priority Area to “Reduce the Incidence of HIV.” The work has the potential to reduce HIV transmission for one of the most highly impacted populations, consistent with National HIV/AIDS Strategy goals to support health equity and contributing to national Ending the HIV Epidemic goals.

PI_NAMEs: HOTTON, ANNA  (contact);MCNULTY, MOIRA

PROGRAM_OFFICER_NAME: SCOTT-SHELDON, LORI ANN JENNIFER

PROJECT_TERMS: Address;AIDS prevention;antiretroviral therapy;Area;barrier to care;Behavior;Behavioral;Black race;Caring;Chicago;Clinic;Clinical;Collaborations;Communities;community advisory board;Community Health;Community Healthcare;Complex;Computer Models;Consensus;contextual factors;Criminal Justice;Data;Data Analyses;Data Sources;Diagnosis;disease transmission;Disparity in diagnosis;Effectiveness of Interventions;Epidemic;Epidemiologic Methods;Ethics;Evaluation;experience;experimental study;Exposure to;Feedback;Focus Groups;Future;Geographic Locations;Goals;health equity;health inequalities;HIV;HIV diagnosis;HIV Infections;HIV/AIDS;housing instability;Human immunodeficiency virus test;implementation barriers;implementation framework;implementation science;implementation strategy;Imprisonment;improved;Incidence;Individual;insight;Intervention;Interview;Link;member;Mental Health;Methods;Modeling;Newly Diagnosed;NIH Office of AIDS Research;Outcome;Pathway interactions;Patients;Pattern;peer;Persons;Phase;Population;Prevention;Process;programs;Public Health;Reach, Effectiveness, Adoption, Implementation, and Maintenance;recruit;Research;Research Priority;Resources;Review Literature;Science;screening;sexual minority men;social health determinants;social structure;stressor;success;therapy development;transmission process;Unemployment;Universities;Viral;virtual;Work

PROJECT_TITLE: Community-Engaged Modeling and Implementation Science to Develop Re-Linkage Interventions for Black Sexual Minority Men with HIV

STUDY_SECTION_NAME: Special Emphasis Panel[ZMH1 ERB-L (06)]


FUNDING_MECHANISM: OTHERS

ORG_CITY: WEST HAVEN

ORG_NAME: VA CONNECTICUT HEALTHCARE SYSTEM

ORG_STATE: CT

PHR: Dr. Bell is requesting renewal of his SRCS for an additional 5 years. During these 5 years he plans to continue to vigorously pursue his research, education, administrative and service mission. Dr. Bell has an international reputation in psychiatric rehabilitation and has been funded by VA RR&D, VA HSR&D, DoD, NIMH, NIDA, NIAAA and NSF. Renewal will allow him to continue his research in 1) vocational rehabilitation, 2) neurocognitive and social cognitive deficits and their relationships to functional impairments, 3) development of assessment instruments, 4) cognitive remediation, and 5) substance abuse rehabilitation. These research activities meet priority healthcare needs for Veterans. Dr. Bell plans to continue his mentorship to train the next generation of clinical researchers, to continue to provide administrative support to the VA research mission by chairing the Human Studies Subcommittee and by serving on VA RR&D review groups, and to continue to directly serve Veterans as Director of an outreach program to Veterans on area college campuses.

PI_NAMEs: BELL, MORRIS D. (contact)

PROJECT_TERMS: Adopted;Adult;Algorithms;Applications Grants;Area;Assessment tool;Award;Book Chapters;career;Chairperson;Child;Cladribine;Classification;Clinical;clinical practice;Clinical Trials;Cognition;Cognitive deficits;Cognitive remediation;college;commercialization;Connecticut;Consultations;Development;disability;Education;Engineering;Enrollment;Evaluation;expedited review;experience;Faculty;Friends;functional disability;Functional impairment;Funding;Future;Grant;Health;Health Priorities;Healthcare;Healthcare Systems;Homogeneously Staining Region;Human;Impaired cognition;indexing;innovation;instrument;interest;International;Intervention;Leadership;Legal patent;Manuals;Measures;Medicine;meetings;member;Mentors;Mentorship;Mission;Movement;Multiple Sclerosis;National Institute of Drug Abuse;National Institute of Mental Health;National Institute on Alcohol Abuse and Alcoholism;Neurocognitive;next generation;outreach;outreach program;pandemic disease;Peer Review;Performance at work;Postdoctoral Fellow;Principal Investigator;programs;Protocols documentation;psychiatric rehabilitation;psychoeducation;Publications;Publishing;rehabilitation research;Rehabilitation therapy;Research;Research Activity;Research Personnel;Schools;Scientist;senior faculty;Services;Shapes;social;social cognition;standard measure;Students;substance abuse rehabilitation;Technology Transfer;telehealth;Testing;Time;Training;Universities;Veterans;visiting scholar;Vocational rehabilitation;Work;Workload;World Health Organization

PROJECT_TITLE: RR&D Senior Research Career Scientist Award

STUDY_SECTION_NAME: Research Career Scientist[RRD7]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Pediatric;Rare Diseases

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: NARRATIVE  During the last ten years, it has become apparent that deregulation or disruption of proteins residing at the Intercalated Disk (ICD), the unique membrane microdomain that mediates the mechanical and electrical coupling of cardiomyocytes, leads to cardiac defects and development of severe or lethal cardiomyopathies. The proposed studies will provide important and novel information about the modulation of a major component of the ICD, N-cadherin, via the enzymatic activity of the obscurin Ser/Thr kinase domain 1. Elucidating the molecular mechanisms that underlie cell-cell adhesion and communication in cardiac muscle during normalcy will allow us to understand how these are altered or compromised during congenital heart disease, and thus enable us to develop new, effective, and targeted therapies.

PI_NAMEs: KONTROGIANNI-KONSTANTOPOULOS, AIKATERINI  (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Address;Adherens Junction;Adhesions;Affect;Affinity;Aging;Aortic Valve Stenosis;Arrhythmogenic Right Ventricular Dysplasia;Binding;Biochemical;Biological;Biological Assay;Calmodulin;Cardiac;Cardiac Myocytes;cardiogenesis;Cardiomyopathies;Catalytic Domain;Cell Communication;Cell-Cell Adhesion;Classification;Communication;congenital heart abnormality;Coupling;Cytoplasmic Tail;Cytoskeletal Proteins;Development;Dilated Cardiomyopathy;Disease;Dominant-Negative Mutation;effective therapy;Electrophysiology (science);Family;Fibronectins;Gene Delivery;Genes;Health;Heart;heart defect;Heart Diseases;Heart failure;Human;Immunoglobulins;In Vitro;in vivo;Injections;Intercalated disc;Kinetics;Knock-in Mouse;Left ventricular non-compaction;Link;Mass Spectrum Analysis;Mechanics;Mediating;member;Membrane;Membrane Microdomains;Missense Mutation;Modeling;Molecular;Morphology;mouse model;Mus;Mutagenesis;Mutate;Mutation;Myocardium;Myosin Light Chain Kinase;N-Cadherin;next generation sequencing;Normalcy;novel;novel therapeutics;obscurin;overexpression;Pathogenesis;Pathogenicity;Patients;phosphoproteomics;Phosphorylation;Phosphotransferases;Physiological;Play;Pre-Clinical Model;Property;Protein Isoforms;Protein Truncation;Proteins;Role;Sarcolemma;Sequence Homology;Signal Transduction;Site;Striated Muscles;Structure;Surface Plasmon Resonance;Tachycardia;targeted treatment;therapy development;Time;Variant;Viral;Work;young adult

PROJECT_TITLE: Obscurin-kinase 1/N-cadherin: a new signaling axis in cardiac structure/function


NIH_SPENDING_CATS: Brain Disorders;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_CITY: Aurora

ORG_NAME: LOHOCLA RESEARCH CORPORATION

ORG_STATE: CO

PHR: Original Project Narrative The U.S. and other countries around the world are facing “dual crises of pain and opioid addiction.” Lohocla Research Corporation has responded to the opioid crisis and medication development challenge by designing, synthesizing and demonstrating, in pre-clinical studies, the efficacy and safety of a non-opiate, non-addictive new chemical entity for treatment of chronic pain. This new chemical entity, called Kindolor, has significant additional benefits of being able to prevent the development of chronic pain if administered soon after tissue injury, including post-operative conditions. Kindolor also has a highly significant “opiate sparing” effect in conditions that may require the use of opiates, since Kindolor demonstrates a strong synergistic effect with morphine. In this grant application we are requesting funds to complete cGMP synthesis and GLP studies necessary for an IND application to the FDA, and given the FDA approval of the IND status, the completion of the first in human, Phase I clinical studies for safety and Phase 2a studies of efficacy to bring our medication to chronic pain sufferers.

PI_NAMEs: TABAKOFF, BORIS  (contact)

PROGRAM_OFFICER_NAME: ACRI, JANE

PROJECT_TERMS: addiction;Adult;Affect;Animal Model;Animals;Applications Grants;Budgets;Cardiovascular system;chronic pain;chronic pain management;Clinical;Clinical Research;clinical trial protocol;Clinical Trials;Country;Cyclic GMP;design;Development;Dose;Drug Design;Drug Kinetics;efficacy study;Enteric-Coated Tablets;experimental study;first-in-human;Formulation;Funding;genotoxicity;Goals;Human;inhibitor;Licensing;manufacturing scale-up;Metabolism;method development;Miniature Swine;Modification;Morphine;N-Methyl-D-Aspartate Receptors;Names;new chemical entity;novel therapeutics;Opiate Addiction;Opioid;opioid abuse;opioid epidemic;opioid use;Oral Administration;osteoarthritis pain;Overdose;Pain;Pain management;pain signal;Peripheral;Pharmaceutical Preparations;Pharmacologic Substance;Phase;phase I trial;Phase Ia Clinical Trial;Population;Postoperative Period;pre-Investigational New Drug meeting;preclinical study;prescription opioid;prevent;Procedures;Process;Rattus;Recovery;Request for Applications;Research;respiratory;response;Safety;safety study;sensory system;Sodium Channel;synthetic opioid;tissue injury;Toxic effect;Toxicokinetics;Toxicology

PROJECT_TITLE: A novel therapeutic to ameliorate chronic pain and reduce opiate use


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Clinical Research;Congenital Structural Anomalies;Digestive Diseases;Liver Disease;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: The Childhood Liver Disease Research Network (ChiLDReN) studies babies, children, and young adults who have rare, mostly cholestatic liver diseases. The researchers will ask patients to participate in studies that will help us: 1) Develop new tests to better diagnose these diseases; 2) Learn more about what causes these diseases, 3) Develop better treatment options for children living with these diseases.

PI_NAMEs: MAGEE, JOHN C (contact)

PROGRAM_OFFICER_NAME: DOO, EDWARD

PROJECT_TERMS: Alagille Syndrome;alpha 1-Antitrypsin Deficiency;Ancillary Study;Bile Acid Biosynthesis Pathway;Biliary Atresia;biomarker development;Charge;Child;Childhood;Cholestasis;Chronic;chronic liver disease;Clinical;Clinical Research;Clinical Trials;Clinical Trials Design;Collaborations;Communication;Conduct Clinical Trials;Data;Data Coordinating Center;data management;Databases;Defect;design;Development;Disease;disease diagnosis;disease model;Enrollment;experience;Faculty;Family;Funding;Future;Genomics;Goals;Human Resources;Infrastructure;Institution;Intervention Studies;Knowledge;Leadership;Learning;Liver diseases;Liver Fibrosis;liver transplantation;Longitudinal cohort study;Michigan;Mitochondria;Monitor;Morbidity - disease rate;National Institute of Diabetes and Digestive and Kidney Diseases;Natural History;neonatal hepatitis;Observational Study;Patient Care;Patients;Phase;primary sclerosing cholangitis;Progressive intrahepatic cholestasis;Protocols documentation;Publications;quality assurance;recruit;Research;Research Design;Research Personnel;research study;Role;Scientist;Site;Societies;success;support network;System;Testing;United States;Universities;web site;Work;working group;young adult

PROJECT_TITLE: Childhood Liver Disease Research Network (ChiLDReN) Scientific and Data Coordinating Center

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-Q (M1)]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Chronic Pain;Contraception/Reproduction;Endometriosis;Genetics;Human Genome;Pain Research;Women's Health Research

ORG_CITY: SAN ANTONIO

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: NARRATIVE Immune dysregulation and inflammation are common features of endometriosis, a benign gynecologic condition that can cause chronic pain, infertility, and myriad other symptoms. Endometriosis commonly co- occurs with inflammatory conditions, but the links between these traits are poorly understood. This proposal comprises two complementary aims that will use human population genetics methods, single cell and spatial genomics, in vitro organoid models and a bioluminescent murine model of endometriosis to identify novel therapeutic opportunities by studying the genes and pathways that link endometriosis and inflammation.

PI_NAMEs: LAWRENSON, KATE  (contact)

PROGRAM_OFFICER_NAME: RIVERS, ROBERT C

PROJECT_TERMS: 3-Dimensional;Adult women;Affect;Age;Anxiety;Apoptosis;Asian ancestry;Asian Women;Asthma;Atlases;Autoimmune Diseases;B-Lymphocytes;Benign;Candidate Disease Gene;candidate identification;CDC42 gene;Cell Proliferation;Cell Survival;Cells;Cervix Uteri;Chronic Fatigue Syndrome;chronic pain;chronic pelvic pain;clinical translation;comorbidity;Data;Data Set;Defecation;Degenerative polyarthritis;Dendritic Cells;Development;Disease;duodenitis;Dyschezia;Dysmenorrhea;Dyspareunia;Dysuria;Endometrial;endometriosis;Endometrium;Environment;Epidemiology;epidemiology study;Epigenetic Process;Epithelial Cells;Epithelium;Estrogens;Ethnic Population;European ancestry;Exposure to;Fibromyalgia;Gastritis;Gene Expression Profiling;Gene Family;Genes;Genetic;genetic risk factor;Genetic study;Genetic Transcription;genome wide association study;genome-wide;Genomics;Germ Lines;Gland;Goals;Gonadal Steroid Hormones;Gynecologic;higher education;Hormonal;hormonal signals;hormone regulation;Hormone Responsive;Hormones;human population genetics;Hypersensitivity;IL1A gene;IL1R1 gene;Immune;Immune signaling;Immune Targeting;Immunologic Surveillance;immunoregulation;In Vitro;in vitro Model;in vivo;in vivo Model;Infectious Mononucleosis;Infertility;Inflammation;Inflammatory;Inflammatory Response Pathway;Inherited;intercellular communication;Interleukin-1;Interleukin-1 Receptors;Interleukins;Irritable Bowel Syndrome;Life;Link;Location;Luteal Phase;Macrophage;Malignant Neoplasms;Mental Depression;Meta-Analysis;Methods;Modeling;Molecular Profiling;mouse model;multiple omics;Muscle Cramp;novel;novel therapeutics;Odds Ratio;Organoids;Pain;Pathogenesis;Pathway interactions;Patients;Penetration;personalized therapeutic;Play;pleiotropism;Population;population based;Pre-Clinical Model;prevent;proliferative phase Menstrual cycle;Proteomics;racial population;receptor expression;recruit;Reporting;reproductive;Research;Research Project Grants;response;Risk;risk sharing;risk variant;Role;Sex Behavior;Signal Transduction;Societies;Symptoms;System;Systems Biology;Testing;Therapeutic;therapeutic target;Tissues;trait;transcriptomics;transgender men;tumor-immune system interactions;Uterine cavity;Uterus;Woman;women versus men;Work

PROJECT_TITLE: Hormonal Influences on Inflammation in Endometriosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-F (50)]


ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

PHR: Suicide and suicide attempts among U.S. Veterans remain a serious concern, as more than 6,000 Veterans die by suicide every year and many more attempt suicide. Current VHA suicide prediction models do not incorporate the rich information relevant to suicide from clinical progress notes. The proposed study will use natural language processing to make this information available for suicide prediction models. The study sets itself apart from other studies in this area by employing the state-of-the-art 3-step Theory of Suicide, which aims to distinguish high-risk Veterans who will attempt suicide from high-risk Veterans who will not attempt suicide. Enhancing VHA's ability to identify Veterans who are most likely to attempt suicide ensures that limited intervention resources can focus on Veterans with the highest needs, before they attempt suicide or die by suicide. The proposed study is well-aligned with priorities for HSR&D research and with VA strategic goals for 2018 – 2024 set out by VA leadership, who listed suicide prevention as “VA's highest clinical priority.”

PI_NAMEs: SOX-HARRIS, ALEX  (contact)

PROJECT_TERMS: Age;Area;Attention;Automated Annotation;Caring;Clinical;clinical encounter;clinical practice;concept mapping;Data;Data Collection;data repository;Data Science;data warehouse;design;Detection;Development;Electronic Health Record;Ensure;Event;Feeling hopeless;Feeling suicidal;Female;Gender;Goals;hands-on learning;high risk;implementation facilitation;improved;Information Retrieval;innovation;Intervention;Knowledge;Language;Leadership;Linguistics;Machine Learning;machine learning algorithm;machine learning model;Maps;Medical;Medicine;Mental Health;Methodology;Methods;Modeling;Natural Language Processing;Nomenclature;novel;Ontology;Pain;Patient Selection;Patients;Performance;Persons;phrases;predictive modeling;psychologic;random forest;Readability;reducing suicide;Research;Resources;Risk Assessment;Risk Factors;risk prediction model;Signal Transduction;Structure;structured data;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;suicide mortality;Suicide prevention;suicide rate;support vector machine;System;Target Populations;Text;text searching;theories;tool;Translating;Veterans;Veterans Health Administration

PROJECT_TITLE: Can suicide theory-guided natural language processing of clinical progress notes improve existing prediction models of Veteran suicide mortality?

STUDY_SECTION_NAME: HSR-4  Mental and Behavioral Health[HSR4]


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Interleukin-1B (IL-1B) has shown conflicting roles in tumor growth and tumor immune rejection across animal models and human clinical trials. Determining when and how regulatory T cells (Tregs) use the decoy receptor IL-1R2 to regulate IL-1B signaling will reveal fundamental information about tumor Treg function and their suppression of other immune cells. IL-1R2 may also serve as a novel therapeutic target for human cancers by selectively depleting tumor Tregs and bolstering tumor immune rejection.

PI_NAMEs: HABRYLO, IRENEUSZ  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Adaptive Immune System;adaptive immunity;Affect;anakinra;angiogenesis;Animal Model;antagonist;anti-PD-1;anti-tumor immune response;Attenuated;Big Data;Biological Assay;Biology;California;cancer immunotherapy;cancer infiltrating T cells;cancer therapy;carcinogenesis;career;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;cell killing;Cell Physiology;Cell surface;Cells;Cellular biology;checkpoint therapy;Chronic;Clinical Trials;Complex;CRISPR/Cas technology;cytokine;Data;engineered T cells;Environment;Event;Experimental Designs;experimental study;Genetic Transcription;Graduate Education;Growth;Health;Human;IL1R1 gene;IL1R2 gene;Immune;Immune Evasion;Immunology;improved;Incidence;Infiltration;Inflammation;Inflammatory;inhibitor;Interleukin-1;Interleukin-1 Receptors;Interleukins;Journals;Kinetics;Label;Malignant Neoplasms;Mediating;meetings;Melanoma;Mentorship;Modeling;Mus;Myelogenous;Myeloid Cells;neoplastic cell;new therapeutic target;novel strategies;novel therapeutic intervention;Organism;Pathway interactions;permissiveness;Physicians;Population;Productivity;protein expression;Qualifying;receptor;Receptor Signaling;Regulatory T-Lymphocyte;Reporter;Reporting;Research;response;Role;Sampling;San Francisco;Science;Scientist;Signal Transduction;single-cell RNA sequencing;Skin;Structure;System;systemic inflammatory response;T cell response;T-Cell Activation;T-Cell Receptor;Technical Expertise;Testing;Time;Tissues;Training;transcriptome sequencing;tumor;tumor growth;Tumor Immunity;Tumor Markers;tumor microenvironment;Universities

PROJECT_TITLE: The role of decoy receptor IL-1R2 in Treg biology and anti-tumor immunity


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Nutrition;Pancreatic Cancer;Rare Diseases

PHR: PROJECT NARRATIVE Altered nutrient availability between tumors and healthy tissues drive differences in the metabolic dependencies of cells in these environments; these differences may be leveraged to control tumor growth in the clinic. Here we identify suppressed pyruvate oxidation is a critical metabolic adaptation of pancreatic cancer cells grown under tumor nutrient stress. Clinically relevant compounds that disrupt the regulation of pyruvate oxidation are already available, and thus the findings of this project have the potential for rapid clinical translation.

PI_NAMEs: SHEEHAN, COLIN  (contact)

PROGRAM_OFFICER_NAME: SCHMIDT, MICHAEL K

PROJECT_TERMS: aerobic glycolysis;Affect;Anabolism;Animals;Biochemical;Biological Assay;Biological Markers;Biological Models;Blood Vessels;cancer cell;cancer type;Carbon;cell growth;Cell Survival;Cells;Citric Acid Cycle;Clinic;clinical translation;clinically relevant;cofactor;Communication;CRISPR interference;CRISPR screen;cytotoxic;Data;Dependence;Disease;Drug Compounding;effective therapy;Environment;Equilibrium;Fermentation;fitness;Formulation;Functional dependence;Genetic;Goals;Growth;Homeostasis;Hypoxia;in vivo;Injections;Intercellular Fluid;knock-down;Lactic acid;Lipids;macromolecule;Malignant neoplasm of pancreas;Mediating;Mediator;Metabolic;metabolic abnormality assessment;Metabolism;metabolomics;Modeling;Mus;NADH;neoplastic cell;normoxia;novel;novel therapeutic intervention;Nucleic Acids;Nutrient;Nutrient availability;oxidation;Oxidation-Reduction;Oxidative Stress;Oxygen;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;Pathway interactions;PDH kinase;Perfusion;Phosphorylation;Phosphotransferases;prevent;Production;Proliferating;Proteins;Proto-Oncogene Proteins c-akt;Pyruvate;pyruvate dehydrogenase;Pyruvate Dehydrogenase Complex;Reactive Oxygen Species;Regulation;response;Role;screening;sensor;Signal Pathway;Signal Transduction;Stress;Testing;therapeutic target;Therapeutically Targetable;Tissues;tumor;tumor growth;tumor microenvironment;Work

PROJECT_TITLE: Role of PDK1 in pancreatic cancer cell fitness under tumor nutrient stress


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: This proposal will determine structural and biochemical understandings of CRISPR adaptation and CRISPR immune signaling pathways. This research is relevant to public health because it will increase our knowledge about fundamental cellular processes, such as integration and bacterial immune signaling pathways. The proposed research is relevant to NIH's mission because it will provide critical insights into CRISPR biology necessary for applications in biotechnology and medicine.

PI_NAMEs: SANTIAGO-FRANGOS, ANDREW  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: acquired immunity;Adaptive Immune System;Address;antimicrobial;Archaea;Archaeal Genome;Area;Award;Bacteria;Bacterial DNA;Bacteriophages;Base Pairing;BCAR1 gene;Biochemical;Biochemistry;Bioinformatics;Biological;Biological Assay;Biology;Biotechnology;Cell Physiology;Cellular Morphology;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Conserved Sequence;COVID-19 detection;Creativeness;Cryoelectron Microscopy;Development;Devices;Diagnostic;DNA;DNA analysis;DNA Integration;DNA Sequence;DNA Sequence Analysis;experimental study;Genetic;genetic information;Genetic Transcription;Genome;Guide RNA;Guilt;Immune;Immune response;Immune signaling;Immune system;immune system function;Immunity;In Vitro;Infection;innovation;insight;Integrase;Integration Host Factors;interest;invention;Knowledge;Life;Ligands;Mediating;Medical;Medicine;microbial;Mission;Motility;novel;nuclease;Nucleic Acids;Nucleotides;Oligonucleotides;Periodicity;Phase;Positioning Attribute;Process;Proteins;Public Health;Research;Resolution;Retrieval;RNA;RNA Processing;Role;Science;Signal Pathway;Signal Transduction;Signaling Molecule;site-specific integration;Specificity;structural biology;Structure;System;Training;Transcription Initiation Site;Transcription Process;Trees;United States National Institutes of Health;Viral;viral detection;viral RNA

PROJECT_TITLE: Mechanisms of CRISPR-mediated immunity and applications beyond editing