NIH_SPENDING_CATS: Aging;Cancer;Cancer Genomics;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Prevention;Women's Health Research

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

ORG_STATE: MA

PHR: PROJECT NARRATIVE DNA methylation aberrancies are hallmarks of colorectal cancer, the third leading cause of cancer death in both men and women in the U.S. Despite the great promise for early detection and intervention, DNA methylation changes in prediagnostic blood are poorly characterized in individuals with colorectal cancer. We propose the largest prospective study to date to characterize the landscape of genome-wide DNA methylation markers associated with colorectal cancer and examine the biological relevance and modifiable potential of DNA methylation for colorectal cancer prevention.

PI_NAMEs: GIANNAKIS, MARIOS ;SONG, MINGYANG  (contact)

PROGRAM_OFFICER_NAME: SIMONDS, NAOKO ISHIBE

PROJECT_TERMS: 3-Dimensional;Aberrant DNA Methylation;accelerated epigenetic aging;Address;Age;age related;Aging;Alcohol consumption;Assessment tool;Biological;Biological Aging;Biology;black women;Blood;Blood specimen;BRAF gene;Cancer Etiology;carcinogenesis;CD8-Positive T-Lymphocytes;Cells;Cessation of life;Chronology;cohort;Collection;Colon;colon cancer patients;Colorectal Cancer;colorectal cancer prevention;colorectal cancer risk;cost efficient;CpG Island Methylator Phenotype;CpG Islands;Data;data integration;Development;Diagnosis;Diagnostic;Diet;DNA;DNA Methylation;Early Diagnosis;Early Intervention;Epidemiology;Epigenetic age;epigenetic aging;Epigenetic Process;epigenome-wide association studies;Escherichia coli;Etiology;exome sequencing;Follow-Up Studies;FOXP3 gene;Fusobacterium nucleatum;Gene Expression;Genetic;genetic variant;genome wide association study;genome-wide;Genomic Instability;Genotype;Germ Lines;Health Professional;Hypermethylation;IGF2 gene;Immune;Immunity;improved;Incidence;Individual;Investigation;Knowledge;Leukocytes;Life Style;lifestyle data;Link;Mediating;men;Mendelian randomization;Meta-Analysis;Methylation;methylation biomarker;Microsatellite Instability;Mitotic;Molecular;molecular marker;Mucous Membrane;Mutation;Nurses' Health Study;Obesity;Participant;Pathway interactions;Performance;peripheral blood;Phenotype;physical inactivity;polygenic risk score;Predisposition;Prevention;prospective;Prospective cohort;Prospective Studies;Quantitative Trait Loci;racial diversity;Regulatory T-Lymphocyte;Risk Factors;risk stratification;Role;RUNX3 gene;Smoking;Somatic Mutation;Subgroup;Tissues;transcriptome sequencing;tumor;Tumor Promoters;Tumor Suppressor Genes;Tumor Tissue;Update;Variant;western diet;Woman;Women's Health

PROJECT_TITLE: Harnessing DNA methylation in peripheral blood for improved colorectal cancer prevention

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 EPH-E (02)]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: BALTIMORE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_FIPS: US

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative This research proposal will develop a new metabolic imaging technique for the human brain, called ‘simultaneous upfield and downfield MR spectroscopic imaging’, which promises to provide a comprehensive window into brain metabolism on commonly available 3T MRI systems. The long-term goal is to disseminate this methodology, including the necessary processing software, to the clinical neuroscience community for the study of multiple neurological and oncological diseases.

PI_NAMEs: BARKER, PETER B (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: 3-Dimensional;Acceleration;Binding;Brain;Brain imaging;brain metabolism;Chemicals;Clinical;clinical application;Communities;Computer software;Data;data acquisition;Development;Disease;experimental study;Frequencies;Future;Goals;healthy volunteer;Human;human imaging;Image;imaging study;Imaging Techniques;improved;in vivo;Magnetic Resonance Imaging;magnetic resonance spectroscopic imaging;Magnetic Resonance Spectroscopy;Maps;Measurement;Measures;Metabolic;metabolic imaging;Methodology;Methods;Nervous System Disorder;neuroimaging;Neurosciences;novel;novel strategies;Oncology;open source;Phase;Physiologic pulse;Physiological;Protons;reconstruction;Relaxation;Reproducibility;Research;Research Proposals;Resolution;Running;Scanning;Side;Signal Transduction;Slice;spectroscopic imaging;Surveys;System;Techniques;Temperature;Time;time use;tool;Uncertainty;Visualization;Water

PROJECT_TITLE: Simultaneous Downfield and Upfield proton MRSI at 3T

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ISB-P (03)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Data Science;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: AMES

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: IOWA STATE UNIVERSITY

ORG_STATE: IA

PHR: PROJECT NARRATIVE This project will lead, enrich, and sustain a community of practice focused on accurate annotation and prediction of protein function. These goals will be achieved by organizing an innovative community challenge, by developing critical infrastructure for expanding and improving function prediction, by increasing interaction among subcommunities, by increasing training opportunities, as well as by widely disseminating scientific findings. All proposed activities will incentivize the community towards reaching the long-term goal of accurately annotating every protein with respect to their residue- and protein-level function in a fine-grained, context-dependent, and causal manner.

PI_NAMEs: FRIEDBERG, IDDO  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Address;Adopted;Algorithms;Amino Acid Sequence;Biological;Biological Assay;Biological Process;career;career development;Communities;Community of Practice;Computational Biology;computer infrastructure;computer scientist;Computer software;Computing Methodologies;Consumption;Data;Data Scientist;Development;Drops;Event;experience;Expert Systems;functional improvement;gene function;Generations;Genes;genome sequencing;genomic data;Genomics;Goals;Grain;improved;Incentives;Information Dissemination;Infrastructure;innovation;interest;interoperability;Journals;Knowledge;Lead;Life;Machine Learning;macromolecule;meetings;Metagenomics;Methods;Modeling;Molecular;Molecular Biology;Nature;Ontology;Open Reading Frames;open source;Performance;Periodicals;Post-Translational Modification Site;prediction algorithm;Productivity;protein function;Proteins;Recommendation;Research Personnel;Scientist;Software Engineering;Structure;symposium;Technology;three dimensional structure;Time;Tissues;tool;training opportunity;Work

PROJECT_TITLE: Fine-grained Annotation of the Protein Universe through a Community of Practice

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Immunotherapy;Prevention

ORG_CITY: PORTLAND

ORG_NAME: MAINEHEALTH

ORG_STATE: ME

PHR: Public Health Relevance Statement: The purpose of this study is to determine the role of myeloid cell-specific ErbB3 signaling in the protection against lymphocyte activation and secondary heart tissue damage in response to inflammation associated with cardiac injury. The anticipated data may lead to the development of novel immunotherapies to cure patients with ischemic cardiac disease.

PI_NAMEs: RYZHOV, SERGEY  (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: Ablation;Activated Lymphocyte;Acute;Area;Binding;Cardiac;CCL20 gene;CCL4 gene;Cell surface;Cells;chemokine;Coculture Techniques;coronary fibrosis;cytotoxic;Data;Dendritic Cells;Development;experimental study;Fibroblasts;Fibrosis;gain of function;Gene Expression;Genetic;Heart;heart cell;Heart Diseases;Heart failure;heart function;Heart Hypertrophy;Heart Injuries;Human;Immune;Immune response;immunoregulation;Immunosuppression;Immunotherapy;Inflammation;Inflammatory;Inflammatory Response;injured;Innate Immune System;inter-individual variation;Ischemia;ITGAX gene;loss of function;Lymphocyte;Lymphocyte Activation;lymphocyte trafficking;Macrophage;Maintenance;Mediating;Molecular;monocyte;mouse model;mRNA Expression;Mus;Myeloid Cell Activation;Myeloid Cells;Myocardial;myocardial damage;Myocardial dysfunction;myocardial injury;Myocardial Ischemia;Myocardial tissue;Myocarditis;Myocardium;Neuregulin 1;Neuregulins;neutralizing antibody;novel;NR4A1 gene;overexpression;paracrine;Pathway interactions;Patients;periostin;Play;pressure;prevent;Prevention;Production;programmed cell death ligand 1;programmed cell death protein 1;programs;protein expression;Proteomics;public health relevance;Regulation;Reperfusion Injury;Reperfusion Therapy;Research;response;Risk Reduction;Role;Signal Transduction;System;T-Cell Activation;Testing;Tissues;Transforming Growth Factor beta;Up-Regulation

PROJECT_TITLE: Neuregulin signaling in myeloid cells

STUDY_SECTION: MPPA

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Drug Abuse (NIDA only);Mental Health;Neurosciences;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Substance Misuse

ORG_CITY: PHILADELPHIA

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: NARRATIVE This proposal, the first of its kind, focuses on understanding the brain and behavioral mechanisms of psilocybin treatment in opioid use disorder. The opioid crisis remains a critical public health issue, and novel treatments are needed to reduce overdose risk. Psilocybin may help by reducing barriers to treatment and ongoing illicit drug use, as well as by increasing adherence to life-saving opioid medications.

PI_NAMEs: CHILDRESS, ANNA ROSE (contact);KAMPMAN, KYLE MATTHEW

PROGRAM_OFFICER_NAME: FEDOTA, JOHN RAPHAEL

PROJECT_TERMS: abuse neglect;Acute;addiction;Adherence;Affect;Affective;Agonist;Alcohol dependence;Amygdaloid structure;barrier to care;Behavior;Behavioral;Behavioral Mechanisms;behavioral response;Brain;Buprenorphine;Cessation of life;Child Abuse;cingulate cortex;Clinical;Clinical Trials;Cognition;comparison control;Control Groups;craving;Cues;Data;depressive symptoms;design;Disease;Dorsal;Dose;Event;Exclusion;experience;Feeling;Fentanyl;flexibility;Functional disorder;Functional Magnetic Resonance Imaging;Future;Globus Pallidus;Hallucinogens;Hour;illicit drug use;Image;Individual;Instruction;Insula of Reil;interest;Life;Link;Measures;Mental Depression;Motivation;Motor;multidisciplinary;neurobehavioral;Neurocognition;Neurocognitive;Neuronal Plasticity;Nicotine Dependence;non-drug;novel;Opioid;opioid epidemic;opioid mortality;opioid overdose;opioid use disorder;Outcome;outreach;Overdose;overdose death;Overdose reduction;overdose risk;Parietal Lobe;Pathway Analysis;Patients;Performance;Pharmaceutical Preparations;Phase;pre-clinical;Prefrontal Cortex;Preparation;prescription opioid;prospective;Psilocybin;Public Health;Randomized;receptor;Recording of previous events;recruit;Regulation;Research;response;Sample Size;Serotonin;smoking addiction;Sorting;statistics;Substance Use Disorder;Therapeutic;tool;Trauma;Ventral Striatum;Visual;Wisconsin;Withdrawal;Work

PROJECT_TITLE: Psilocybin: Capturing brain mechanisms of motivation and neurocognition in individuals with opioid use disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 BSW-N (M2)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breast Cancer;Cancer;Immunization;Neurosciences;Orphan Drug;Rare Diseases;Women's Health Research

ORG_CITY: BIRMINGHAM

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative: Antibody-drug conjugates (ADCs) are promising emergent cancer therapies that precisely deliver cytotoxic payloads to targeted tumor cells. Even so, the in vivo usage of ADCs has various limitations, such as on-target/off-tumor toxicity, poor brain delivery, acquired therapy resistance, and low effectiveness in target tumors with low antigen expression. We intend to overcome these issues using PMPC-polymer engineering technology developed by our team.

PI_NAMEs: KAMATA, MASAKAZU  (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: Address;Affinity;Animals;anti-cancer;Antibodies;antibody engineering;antibody-dependent cell cytotoxicity;Antibody-drug conjugates;anticancer activity;Antigens;Antineoplastic Agents;B-Cell Lymphomas;Biological Process;Bioluminescence;biomaterial compatibility;Blood;Blood - brain barrier anatomy;blood-brain barrier penetration;Brain;Breast Cancer cell line;breast cancer metastasis;Breast Cancer Treatment;BT 474;cancer cell;Cancer Control;cancer therapy;Cancerous;Cell Line;Cells;Central Nervous System;Chemicals;choline transporter;Cholinergic Receptors;Circulation;Clinical;clinical translation;clinically relevant;Crosslinker;cytotoxic;cytotoxicity;Cytotoxin;Data;Disease;Drug resistance;Effectiveness;efficacy validation;Endothelial Cells;Engineering;Ensure;Environment;Epidermal Growth Factor Receptor;Epitopes;ERBB2 gene;Exhibits;Fc Receptor;FDA approved;Gene Amplification;Genes;Grant;Human;humanized mouse;Immune;Immune response;Immunohistochemistry;Immunologic Surveillance;Immunologics;Impairment;improved;In Vitro;in vivo;Laboratories;Legal patent;Location;lymph nodes;Maintenance;Malignant Breast Neoplasm;Malignant Epithelial Cell;Malignant neoplasm of ovary;Malignant Neoplasms;malignant stomach neoplasm;MDA MB 231;Metastatic breast cancer;Metastatic malignant neoplasm to brain;Metastatic Neoplasm to the Central Nervous System;Modification;Monoclonal Antibodies;mouse model;MS4A1 gene;Mus;Mutate;nanocapsule;Nanotechnology;Nature;Neoplasm Metastasis;neoplastic cell;new technology;Non-Small-Cell Lung Carcinoma;nonhuman primate;novel;novel strategies;patient derived xenograft model;Patients;Penetration;Pharmaceutical Preparations;Phosphorylcholine;Polymers;programs;Property;Protein Overexpression;Rattus;receptor binding;Regimen;Resistance;response;rituximab;selective expression;side effect;Site;Structure;Survival Rate;synthetic polymer Bioplex;Technology;technology development;Testing;Therapeutic;Therapeutic antibodies;Therapeutic Index;therapy resistant;Tissues;Toxic effect;transcriptomics;transcytosis;Trastuzumab;tumor;Tumor Antigens;Use Effectiveness;Work;Xenograft procedure

PROJECT_TITLE: The resurgence of antibody-drug conjugates via PMPC-polymer engineering

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-U (55)]


PHR: Project Narrative: Single-stranded DNA lesions (SSLs) are among the most abundant types of DNA damage. Defects in SSL repair pose a mutagenic threat and a potential cancer vulnerability. This project will uncover how epigenetic regulation of SSL repair through alternatively spliced macroH2A1 histone variants impacts mutation burden, tumor development and cancer treatment responses.

PI_NAMEs: OBERDOERFFER, PHILIPP  (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: adduct;Affect;Alkylating Agents;Alternative Splicing;base;Binding;Biochemistry;Biological Assay;Biology;cancer cell;Cancer cell line;cancer genome;Cancer Model;cancer therapy;cancer type;Cells;Chromatin;Complex;Data;Defect;Dependence;Detection;Development;Disease;DNA;DNA Damage;DNA Double Strand Break;DNA lesion;DNA Single Strand Break;Double Strand Break Repair;Ensure;Environment;Epigenetic Process;epigenetic regulation;Event;Excision;Genes;Genetic Transcription;Genome;genome integrity;genome-wide analysis;genomic aberrations;Genomic approach;Genomic Segment;Genomics;Health;Histone H2A;Histones;Human;imaging approach;Impairment;improved;inhibitor;innovation;insight;Kinetics;Knowledge;Lesion;macroH2A histone;Maintenance;Malignant Neoplasms;Modeling;Molecular;mouse model;Mutagenesis;Mutation;Organoids;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;Poly Adenosine Diphosphate Ribose;Poly(ADP-ribose) Polymerases;Polymerase;Positioning Attribute;Process;Protein Isoforms;Proteins;repaired;Reporter;Research Personnel;Resolution;response;RNA Splicing;Role;Single-Stranded DNA;Somatic Cell;Source;targeted treatment;Testing;TOP1 gene;Topoisomerase;treatment response;tumor;tumorigenesis;unpublished works;Variant

PROJECT_TITLE: Epigenetic mechanisms controlling single-stranded DNA lesion sensitivity and mutagenesis

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Lung;Lung Cancer;Networking and Information Technology R&D (NITRD);Radiation Oncology

PHR: NARRATIVE This proposal will develop and translate a novel imaging method called Kilo-voltage Real-time Imaging using Scattered Photons (KRISP) for real-time 3D lung tumor motion tracking and demonstrate its feasibility and advantages in lung cancer radiation therapy. The proposed study will have a high clinical impact, as it will overcome a major hurdle in 4D radiation therapy, enabling this novel therapeutic approach to reduce margins and therefore normal tissue complications in lung cancer radiotherapy, while maintaining tumor control.

PI_NAMEs: JIA, XUN  (contact);YANG, KAI

PROGRAM_OFFICER_NAME: LIN, CHARLES

PROJECT_TERMS: 3-Dimensional;Address;Adoption;Anatomy;Bronchial Tree;Cancer Etiology;cancer imaging;cancer radiation therapy;cancer therapy;Cancerous;Cardiac;Cessation of life;chemotherapy;Chest;Chest wall structure;Clinic;Clinical;clinically significant;Collimator;Complication;Computer software;computer studies;cone-beam computed tomography;cost;Data;data analysis pipeline;deep learning;Detection;Development;Diameter;Dose;Dose Rate;Effectiveness;Engineering;Ensure;Esophagus;Event;experimental study;gastrointestinal;General Hospitals;Geometry;Goals;Image;image reconstruction;imaging modality;Imaging technology;Immunotherapy;Implant;improved;industry partner;innovation;invention;Joints;Lesion;Lung;Lung Neoplasms;Magnetic Resonance Imaging;Malignant neoplasm of lung;Malignant Neoplasms;Massachusetts;Measures;Medical;Methods;Motion;Nature;Normal tissue morphology;novel;novel therapeutic intervention;Operative Surgical Procedures;Outcome;Pain;Patient risk;Patients;Penetration;Performance;Peripheral;Phase;Photons;Physics;Plant Leaves;Pneumothorax;Positioning Attribute;Probability;Procedures;prototype;Radiation;radiation delivery;Radiation therapy;real-time images;Reporting;Research;Resolution;respiratory;response;Rib Fractures;Roentgen Rays;Scanning;Scheme;Site;Skin;software development;software systems;Solid;System;Systems Integration;Techniques;Technology;Time;Toxic effect;Trachea;Translating;Translations;tumor;Tumor Volume;Uncertainty;Universities;Validation;X-Ray Medical Imaging

PROJECT_TITLE: Real time scattered x-ray imaging for tumor motion tracking in radiotherapy.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CTH-E (57)]


NIH_SPENDING_CATS: Cancer

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: NARRATIVE Drugs developed to selectively block the oncogenic kinase BRAF often exhibit a mysterious phenomenon called paradoxical activation in which they fail to inhibit and instead increase BRAF activity. This project uses new biophysical approaches to dissect the molecular mechanisms underlying paradoxical activation with the goal of guiding the design of new drugs that more effectively block BRAF activity.

PI_NAMEs: LEVINSON, NICHOLAS MARK (contact)

PROGRAM_OFFICER_NAME: JOHNSON, ERIC MICHAEL

PROJECT_TERMS: Active Sites;Address;Affinity;Automobile Driving;Binding;biophysical techniques;BRAF gene;Cancer cell line;Cells;Classification;Clinical;Clinical Trials;Colon Carcinoma;Complex;Coupled;Coupling;Cryoelectron Microscopy;Curiosities;Data;Data Set;design;Development;dimer;Dimerization;Drug resistance;Electrons;Event;Exhibits;experimental study;Flow Cytometry;Fluorescence Resonance Energy Transfer;Generations;Goals;Homo;inhibitor;insight;Link;Malignant neoplasm of thyroid;MAP Kinase Gene;MAPK Signaling Pathway Pathway;Maps;Measurement;Measures;Mediating;Melanoma;Melanoma patient;Modeling;Molecular;Molecular Conformation;monomer;mutant;Mutation;Neoplasm Metastasis;novel;novel therapeutics;Oncogenic;Patients;Pharmaceutical Preparations;Phosphotransferases;Property;Protein Kinase;Proteins;Proto-Oncogene Proteins B-raf;raf Kinases;reconstitution;recruit;Resistance;Resistance development;resistance mutation;Role;scaffold;Scaffolding Protein;Shapes;Signal Pathway;Signal Transduction;Structure-Activity Relationship;System;Testing;Thermodynamics;tumor;Work

PROJECT_TITLE: Allosteric mechanisms driving paradoxical activation of RAF kinases

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Aging;Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Clinical Research;Neurosciences;Rehabilitation

ORG_CITY: CHARLESTON

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Understanding why speech recognition is slower for older adults than younger adults could help address common age-related listening and memory difficulties. Our research examines how quickly information is collected and how much information is needed for speech to be understood in noise. We will study the brain systems that support recognition of words based on incomplete fragments to better understand why word recognition is slower for many older adults.

PI_NAMEs: VADEN, KENNETH I. (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Accounting;Acoustics;Address;Adopted;Adult;Affect;age difference;age related;age related decline;Aging;aging population;Atrophic;Brain;Brain imaging;Brain region;Central Nervous System;Clinical;Communication difficulty;Cues;Data;Decision Making;Delayed Memory;Diffusion;Environment;Exhibits;experimental study;Fatigue;Functional Magnetic Resonance Imaging;Goals;gray matter;Height;human old age (65+);Image;imaging study;Impaired cognition;improved;Individual;Knowledge;Link;Literature;Measures;Mediating;member;Memory;memory encoding;memory recognition;neural;neuroimaging;Noise;novel;older adult;Participant;Performance;Process;programs;Protocols documentation;Public Health;Recommendation;rehabilitation strategy;Research;Sensory;Social isolation;Speech;Speech Delay;speech in noise;speech recognition;Speed;Support System;System;Testing;theories;Thinness;Variant;Visual;white matter;young adult

PROJECT_TITLE: Aging Neural Systems and Communication Difficulties

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


NIH_SPENDING_CATS: Biotechnology;Cancer;Immunotherapy

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: NARRATIVE Cancer evades the immune system by harvesting mitochondria of immune cells via nanoscale tentacles or tunneling nanotubes. Here we address this major challenge by delivering exogenous mitochondria to the T cells and combing these supercharged T cells with novel inhibitors that block the ability of cancer cells to form tunneling nanotubes. We will test whether a combination therapy with immune checkpoint inhibitor enhances antitumor outcomes.

PI_NAMEs: SENGUPTA, SHILADITYA  (contact)

PROGRAM_OFFICER_NAME: SOMMERS, CONNIE L

PROJECT_TERMS: 4T1;Actins;Address;B-Cell Acute Lymphoblastic Leukemia;Bone Marrow;Breast Cancer Cell;cancer cell;Cancer Center;CD19 gene;CD8-Positive T-Lymphocytes;Cell Communication;Cell Culture Techniques;Cell Death;Cell Therapy;Cells;checkpoint inhibition;chimeric antigen receptor T cells;Clinical;Clinical Data;Clinical Research;Coculture Techniques;combinatorial;Combined Modality Therapy;Complex;confocal imaging;CRISPR/Cas technology;Cryoelectron Microscopy;Data;DNA sequencing;effector T cell;Electrons;Engineering;Exhibits;Flow Cytometry;Genus Hippocampus;Goals;Harvest;Hour;Human;Image;Immune;Immune checkpoint inhibitor;Immune Evasion;immune function;Immune system;Immunocompetent;Immunologic Tests;immunological status;Immunologics;Immunotherapeutic agent;Immunotherapy;Impairment;improved;improved outcome;in vivo;Incubated;Infusion procedures;inhibitor;insight;Knowledge;Label;Malignant Neoplasms;Mediating;Melanoma Cell;Memory;Metabolic;meter;Methods;Mitochondria;Mitochondrial DNA;Molecular Profiling;mouse model;Mus;nano;nanoscale;Nanotechnology;Nanotubes;Nature;novel;organelle transplantation;Organelles;Outcome;Patients;Penetration;Pharmaceutical Preparations;Play;Publishing;Regimen;Research;response;Role;safety testing;Scanning;Science;Small Interfering RNA;small molecule;Stromal Cells;Structure;survival outcome;System;T-Lymphocyte;Technology;Testing;trafficking;transcriptome sequencing;tumor;Tumor Escape;tumor immunology;tumor progression;Tumor-Infiltrating Lymphocytes

PROJECT_TITLE: Combinatorial application of nanoscale technologies to target a novel mechanism of immune evasion by cancer cells


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: Project Narrative Immune responses to infection depend on the proper function and expansion of antigen-specific T cells, a process that can go awry when T cells recognize auto-antigens and cause autoimmunity in diseases such as multiple sclerosis. The function of T cells is dependent on the activity of channels in the cell membrane that transport charged ions in and out of cells, and we identified a subunit of the sodium/potassium ATPase as an important new regulator of T cell function. In this proposal, we will determine the molecular function of a sodium/potassium ATPase subunit in T cells and its role in autoimmune inflammation in a preclinical model of multiple sclerosis, which is essential to assess the suitability of this sodium/potassium ATPase subunit as a drug target.

PI_NAMEs: FESKE, STEFAN  (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: Acute;adaptive immunity;Address;Affect;antigen-specific T cells;Antigens;antiviral immunity;Apoptosis;ATP1A1 gene;ATP1A3 gene;Attenuated;Autoantigens;Autoimmune;Autoimmune Diseases;autoimmune inflammation;Autoimmunity;Brain;Calcium;Cardiovascular Diseases;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Cycle;cell mediated immune response;Cell membrane;Cell Physiology;Cells;Cellular biology;Cellular Immunity;Cellular Metabolic Process;channel blockers;Charge;Clinical;Clonal Expansion;Complex;conditional knockout;Contracts;Coupled;Data;Development;Disease;drug discovery;Drug Targeting;Energy-Generating Resources;Experimental Autoimmune Encephalomyelitis;experimental study;FDA approved;Foundations;Functional disorder;Genes;Genetic Screening;Goals;Heart;Human;Immune;Immune response;Immune system;Immunologics;Immunotherapy;Impairment;In Vitro;in vivo;Infection;Inflammation;Inflammatory;Ion Channel;Ions;K ATPase;Knockout Mice;Knowledge;Location;Mediating;Membrane Lipids;Membrane Potentials;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Modeling;Molecular;Multiple Sclerosis;Multiprotein Complexes;Mus;Muscle Fibers;Na(+)-K(+)-Exchanging ATPase;neuronal excitability;Neurons;neuropsychiatric disorder;novel;Nutrient;Pharmaceutical Preparations;Physiological;Play;Potassium;potassium ion;Pre-Clinical Model;prevent;Process;Proteins;Pump;Regulation;Research;Role;selective expression;Signal Transduction;Sodium;sodium ion;Symptoms;T-Cell Proliferation;T-Lymphocyte;Tissues;transcriptomics;translational goal;Transmembrane Transport;virtual;Virus;Virus Diseases

PROJECT_TITLE: ATP1B3: novel regulator of T cell-mediated immunity

STUDY_SECTION: CMIB

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


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: NARRATIVE Loss of function mutations in the genes encoding KRIT1 (CCM1), CCM2 (OSM), or CCM3 (PDCD10) cause Cerebral Cavernous Malformations (CCM). The loss of function of each of these proteins is therefore directly associated with stroke, focal neurological defects, seizures and vascular abnormalities. The goal of this application is to understand the molecular underpinnings for normal function of these proteins as regulators of the MAP kinase kinase kinase, MEKK3.

PI_NAMEs: BOGGON, TITUS JONATHON (contact);CALDERWOOD, DAVID A

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Address;Animal Model;Belief;Binding;Biochemical;biochemical model;Biological Assay;Biological Models;biophysical analysis;biophysical properties;Blood Vessels;CCM1 gene;Cell model;cerebral cavernous malformations;Circulation;Complex;Cryoelectron Microscopy;Crystallography;Data;Defect;Development;Disease;Embryo;Genes;Goals;Heart;Individual;Knock-out;Knockout Mice;Knowledge;Laboratories;loss of function;loss of function mutation;MAP Kinase Kinase Kinase;MAP Kinase Modules;MAPK7 gene;member;Mitogen-Activated Protein Kinases;Modeling;Molecular;multicatalytic endopeptidase complex;Mutation;N-terminal;Neurologic;Nonsense-Mediated Decay;Outcome;Pathway interactions;Phenotype;Phosphotransferases;protein complex;Protein Deficiency;protein function;protein protein interaction;Proteins;recruit;Recurrence;Regulation;Research;Role;scaffold;Seizures;Signal Pathway;Signal Transduction;Signaling Protein;stoichiometry;Stroke;Structural Models;Structure;Tertiary Protein Structure;Testing;vascular abnormality;Vascular Endothelium;Zebrafish

PROJECT_TITLE: Signaling mechanisms of the cerebral cavernous malformations protein complex

STUDY_SECTION: BBHV

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


ADMINISTERING_IC: HS

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF MISSOURI KANSAS CITY

ORG_STATE: MO

PHR: Project Narrative This project will observe the screening and treatment seeking experiences of approximately 600 rape survivors. This information will be used to develop more effective rape screening and referral programs.

PI_NAMEs: ANDERSON, RAEANN  (contact)

PROGRAM_OFFICER_NAME: CHEW, EMILY

PROJECT_TITLE: Understanding the screening to care transition for marginalized rape survivors

STUDY_SECTION: HEOR

STUDY_SECTION_NAME: Healthcare Effectiveness and Outcomes Research[HEOR]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Nutrition;Physical Activity

ORG_CITY: DURHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Relevance Obesity, diabetes and closely related metabolic disorders are associated with impaired energy metabolism and damage to intracellular engines known as mitochondria. Dysfunction of these engines can contribute to elevated blood sugar levels, heart failure and diminished exercise tolerance. This project examines processes responsible for maintaining mitochondrial health and resilience in skeletal muscle and heart to promote physical fitness and defend against metabolic diseases.

PI_NAMEs: MUOIO, DEBORAH M (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Acetyl Coenzyme A;Acyl Coenzyme A;acylcarnitine;Aerobic Exercise;age related;Area;beta-Hydroxybutyrate;Bioenergetics;Biogenesis;Biological Assay;Biological Markers;Blood;Blood Glucose;Carbon;Cardiometabolic Disease;cardiometabolism;Catabolism;Cell Respiration;Coenzyme A;cofactor;Diabetes Mellitus;Diagnostic;diagnostic platform;Energy Metabolism;Enzymes;Exercise;Exercise Tolerance;exercise training;FADH2;Fasting;fatty acid oxidation;Fatty Acids;flexibility;Functional disorder;Genetic Engineering;Genetically Engineered Mouse;Glucose;Grant;Health;Heart;Heart failure;Homeostasis;Impairment;In Vitro;insight;Investigation;Ketones;Laboratories;Levocarnitine;Lipids;Mass Spectrum Analysis;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;metabolic fitness;metabolic phenotype;metabolomics;Mitochondria;mitochondrial fitness;Molecular;Muscle;Muscle Mitochondria;NADH;Natural regeneration;Obesity;Outcome;overexpression;oxidation;Oxidoreductase;Pathway interactions;Performance;Physical Fitness;Play;Population;preclinical study;Process;Proteomics;Pyruvate;pyruvate dehydrogenase;Research;resilience;respiratory;Role;Skeletal Muscle;stable isotope;stem;Stress;Stress Tests;System;Tissues;Tracer;Transcription Coactivator;Work

PROJECT_TITLE: Mechanisms of lipid-induced bioenergetic stress in muscle

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: WASHINGTON

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative  The provision of low-value (quality) care, defined as services that provide little clinical benefit relative to their cost, has reached epidemic proportions in the US accounting for more than $300 billion in health care expenditures annually (Kozeara 2020). Private Medicare Advantage (MA) plans have unique toolkit which can be employed to curb the use the low-value care whereas such options are not available in traditional Medicare (TM). Our comparisons of MA-HMO vs TM and MA-PPO vs TM will provide new insights as to whether specific MA plans are effective in reducing the use of low-value care for early-stage breast cancer.

PI_NAMEs: MITCHELL, JEAN M (contact)

PROGRAM_OFFICER_NAME: ZHANG, XINZHI

PROJECT_TITLE: Evaluating Use and Expenditures on Low Quality Breast Cancer Care in the Medicare Program


NIH_SPENDING_CATS: Genetics;Human Fetal Tissue;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: GENETICS

PHR: Project narrative This project will advance our understanding of how neural cells of the cerebral cortex are generated and organized. It will thus, further an understanding of the etiology of neurodevelopmental disorders, including intellectual disability, microcephaly, and autism. Therefore, this study may eventually help in the development of diagnostic and therapeutic options for broad neurological disorders.

PI_NAMEs: SILVER, DEBRA  (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Active Biological Transport;Address;autism spectrum disorder;Basal Cell;Brain;Cell Communication;Cell Physiology;Cells;Cellular Morphology;Cerebral cortex;Chromosome Mapping;Collagen Receptors;Cytoplasm;Cytoskeleton;Development;diagnostic development;Disease;Distal;Dynein ATPase;Embryo;Etiology;excitatory neuron;Exhibits;Extracellular Matrix;Funding;Gene Expression;Gene Expression Regulation;Goals;Grant;Human;human fetal brain;Image;in vivo;inhibitory neuron;insight;Intellectual functioning disability;Interneurons;Label;Link;Measures;Mediating;Meninges;Messenger RNA;meter;Methods;Microcephaly;migration;Molecular;Morphology;Motor;mouse development;Mus;nerve stem cell;Nervous System;Nervous System Disorder;neural;Neurodevelopmental Disorder;neurogenesis;Neuroglia;Neurons;novel;Paracrine Communication;Positioning Attribute;Process;Proteins;Proteome;Proteomics;Radial;Reporter;Resolution;RNA;Role;segregation;Signal Transduction;Signaling Molecule;Source;stem cell function;Structure;Subcellular Fractions;Testing;Therapeutic;tool;Transcript;transcriptome;Translating;Translations

PROJECT_TITLE: Distal mRNA localization and translation in neural stem cells of the developing brain

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


NIH_SPENDING_CATS: Clinical Research;Infectious Diseases;Pediatric;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: VICTORIA

ORG_COUNTRY: CANADA

ORG_FIPS: CA

ORG_NAME: UNIVERSITY OF VICTORIA

ORG_STATE: BC

ORG_ZIPCODE: V8P 5C2

PHR: PROJECT NARRATIVE Syphilis affects millions of people worldwide, and its global rates are on the rise. Current diagnostic tests for syphilis are non-ideal, and having a better diagnostic test would lead to more infections being detected and a decreased incidence of disease. In the current proposal we will extend the performance testing of our promising, newly developed syphilis diagnostic platform that is highly specific for detection of infectious and congenital syphilis and can be translated to a point-of-care test format, to aid in achieving the goal of decreasing the incidence of syphilis in the US and worldwide.

PI_NAMEs: CAMERON, CAROLINE E (contact)

PROGRAM_OFFICER_NAME: GLOCK, JONATHAN A

PROJECT_TERMS: accurate diagnosis;Affect;Africa;Algorithms;Antibodies;antibody detection;antibody transfer;Antigens;Area;Arthritis;Australia;Belgium;Canada;Characteristics;China;Clinic;clinic ready;Clinic Visits;Clinical;clinical diagnosis;Congenital Syphilis;Country;Detection;Development;Diagnosis;Diagnostic;diagnostic assay;diagnostic platform;Diagnostic tests;Disease;disease diagnosis;Enzyme Immunoassay;Europe;Exhibits;Fluorescent Treponemal Antibody-Absorption Test;follow-up;Goals;Immune response;Immunoassay;Incidence;Individual;Infection;Laboratories;Laboratory Research;Latin America;Life;Lupus;Mass Spectrum Analysis;Maternal antibody;Methods;Modality;Monoclonal Antibodies;Names;Nature;Newborn Infant;Oral;pathogen;Pathogen detection;Patients;Peptides;Performance;performance tests;Persons;Plasma;point of care;point of care testing;Population;Pregnancy;Process;prospective;Reagent;Research;Resource-limited setting;Sampling;screening;self testing;Sensitivity and Specificity;Serodiagnoses;Serology;Serology test;Serum;Sexually Transmitted Diseases;Staging;Swab;Symptoms;Syphilis;Syphilis Serodiagnosis;Technology;Test Result;Testing;Time;Translating;Treatment Failure;Treponema pallidum;United States;Urine;Visit;Vulnerable Populations;Yaws

PROJECT_TITLE: Development of a Direct Diagnostic Test for Infectious and Congenital Syphilis

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 FDS-M (M1)]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Arthritis;Behavioral and Social Science;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Complementary and Integrative Health;Disability Research;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Nutrition;Obesity;Osteoarthritis;Pain Research;Physical Activity;Prevention;Rehabilitation;Telehealth

ORG_CITY: WINSTON-SALEM

ORG_DEPT: MISCELLANEOUS

ORG_NAME: WAKE FOREST UNIVERSITY

PHR: PROJECT NARRATIVE Chronic pain is a common experience for many older adults, and it powerfully affects a person’s ability to live independently and with a high quality of life. This project will investigate whether an in-home program informed by psychology and involving increasing physical activity while sitting less, bonding with a group of peers, and reducing body weight can help to improve the physical activity levels and pain symptoms of older adults living with chronic pain. Our long-range goal is to develop a scalable and accessible program that can improve pain symptoms of many older adults at home.

PI_NAMEs: BROOKS, AMBER KELLER;FANNING, JASON  (contact)

PROGRAM_OFFICER_NAME: RICE, ELISE

PROJECT_TERMS: Accelerometer;addiction;Address;Aerobic Exercise;Affect;age related;Aging;American;Behavior;behavior change;Behavior Therapy;Behavioral;Behavioral Medicine;Body Weight;Body Weight decreased;Caloric Restriction;Calories;Chronic;chronic pain;Cognitive;Companions;craving;Devices;Diet;dietary;Effectiveness;effectiveness trial;efficacy evaluation;efficacy testing;efficacy trial;exercise intervention;experience;Feedback;functional independence;Future;Goals;Guidelines;Health;health related quality of life;Healthcare;Helping to End Addiction Long-term;Hip Osteoarthritis;Home;human old age (65+);Hunger;improved;Individual;Inflammation;Intervention;Knee Osteoarthritis;Learning Skill;Maintenance;Measures;Mediating;Mediator;mHealth;Modeling;Monitor;Morbidity - disease rate;Movement;non-opioid analgesic;Obesity;older adult;opioid use;osteoarthritis pain;Outcome;Pain;pain catastrophizing;Pain intensity;Pain interference;Pain management;Pain Measurement;pain outcome;pain reduction;pain symptom;Participant;Pattern;peer;peer coaching;Peer Group;Persons;Pharmaceutical Preparations;Physical activity;Physical Function;pilot trial;primary outcome;Program Accessibility;programs;Psychological reinforcement;Psychology;psychosocial;Quality of life;Randomized;randomized trial;Randomized, Controlled Trials;recruit;remote delivery;remote group;Research;Risk;Sampling;secondary outcome;sedentary;sedentary lifestyle;Self Determination;Self Efficacy;Series;Site;social;social attachment;Social Interaction;Social isolation;social learning;Stress;Students;Symptoms;Technology;technology intervention;Testing;theories;therapy design;Time;Training;treatment as usual;Treatment Efficacy;undergraduate student;United States National Institutes of Health;videoconference;Weight Gain;weight maintenance;Weight maintenance regimen;wireless;Work

PROJECT_TITLE: A Mobile Health Behavior Intervention to Reduce Pain and Improve Health-III (MORPH-III)

STUDY_SECTION: BMHO

STUDY_SECTION_NAME: Biobehavioral Medicine and Health Outcomes Study Section[BMHO]


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Digestive Diseases;Immunization;Microbiome;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Women's Health Research

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE Mounting evidence links perturbations in early life host-microbiota interactions with increased susceptibility to immune-mediated diseases later in life, yet we lack a mechanistic understanding of how mutually beneficial relationships between gut bacteria and the neonatal immune system are formed. Building from our discovery that maternal antibodies, delivered via breastfeeding, are key regulators of intestinal homeostasis, this proposal seeks to define the cellular and molecular mechanisms by which maternal antibodies restrain aberrant immune responses to gut bacteria in early life. The resulting data will advance our understanding of the immunological processes that regulate nascent host-microbiota interactions, thereby aiding in our ability to manipulate mucosal immune responses in early life to promote long-term health.

PI_NAMEs: KOCH, MEGHAN ANNE (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: adaptive immune response;Adult;Animals;anti-microbial peptide;Antibodies;antigen binding;Antigen-Antibody Complex;Antigens;Area;B-Lymphocytes;Bacteria;Benign;Binding;Breast Feeding;CD4 Positive T Lymphocytes;cell type;Cells;Chemicals;chemokine;Colitis;commensal bacteria;commensal microbes;Complement Activation;Complement Receptor;Data;Dendritic Cells;Development;dietary;Disease;draining lymph node;Education;Equilibrium;Fc domain;Fc Receptor;feeding;Flow Cytometry;Food;Fostering;gastrointestinal epithelium;Goals;gut bacteria;gut inflammation;gut microbes;Health;Health Promotion;Helper-Inducer T-Lymphocyte;Homeostasis;host microbiota;host-microbe interactions;Human;Human Milk;Hypersensitivity;IgG1;IgG3;Immune;immune health;Immune response;Immune System Diseases;Immunity;Immunoglobulin A;Immunoglobulin G;Immunologics;Infant;Inflammation;Inflammatory Bowel Diseases;Inflammatory Response;Ingestion;innovation;insight;intestinal homeostasis;Intestines;Knowledge;Lactobacillus;Lead;Life;Ligation;Link;Maternal antibody;Mediating;mesenteric lymph node;Metabolic dysfunction;microbiota;microbiota composition;microorganism antigen;Milk;Molecular;Morbidity - disease rate;Mothers;mouse model;Mucosal Immune Responses;Mucosal Immune System;Mucosal Immunity;Mucous body substance;Mucous Membrane;mutualism;Neonatal;neonatal immune system;neonatal immunity;neonate;neutralizing antibody;nutrition;offspring;Oral Administration;Ovalbumin;pathogen;Play;Predisposition;prevent;Process;Production;RANTES;receptor function;recruit;Research;resident commensals;response;restraint;Role;Severity of illness;Shapes;Signal Pathway;Signal Transduction;Site;Solid;Specificity;Structure of germinal center of lymph node;suckling;T cell response;Testing;Transgenic Mice;transmission process;Weaning;Work;wound;XCR1 gene

PROJECT_TITLE: Breastmilk antibodies regulate neonatal immunity to the microbiota

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Project Narrative This project aims to develop efficient quantitative model-based image reconstruction algorithms for X-ray- induced acoustic computed tomography (XACT) to facilitate dose monitoring during radiotherapy in clinics. This project addresses the algorithmic challenges (limited view artifacts, absence of quantitative dose information, and lack of the capability of correcting for acoustic heterogeneity in the reconstructed dose maps) in the path of the clinical translation of XACT and in combination with the advanced instrumentation being developed as part of the Unit Director’s R37 award, the success of the proposed will expedite the clinical translation of XACT as a next-generation modality for radiation dosimetry as well as radiography. To achieve real-time/near real-time dosimetry capability, the developed reconstruction algorithms will be parallelized using graphics processing units (GPUs).

PI_NAMEs: PANDEY, PRABODH KUMAR (contact)

PROGRAM_OFFICER_NAME: TATA, DARAYASH B

PROJECT_TERMS: absorption;Acceleration;Acoustics;Address;Adopted;Affect;Algorithms;American Cancer Society;Award;Biomedical Computing;biomedical imaging;cancer radiation therapy;cancer therapy;Characteristics;Clinic;Clinical;Clinical Pathways;clinical translation;Computers and Advanced Instrumentation;Creativeness;Deposition;Dose;dose information;dosimetry;experience;Funding;Goals;Grant;Heterogeneity;Human Resources;image reconstruction;in vivo;Maps;Modality;Modeling;Monitor;Morphologic artifacts;next generation;Noise;parallelization;Physics;Physiologic pulse;post-doctoral training;Principal Investigator;proton beam;proton therapy;Protons;Qualifying;Radiation therapy;radiological imaging;Radiometry;reconstruction;Research;Roentgen Rays;Scientist;Seasons;Signal Transduction;Site;success;Techniques;Time;Tissues;tomography;Transducers;tumor;Ultrasonic Transducer;United States National Institutes of Health;X-Ray Computed Tomography

PROJECT_TITLE: Quantitative in vivo dosimetry for radiotherapy using model-based X-ray-induced acoustic computed tomography

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-1 (M2)]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Genetics;Heart Disease;Human Genome;Prevention;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Abdominal aortic aneurysms (AAA) are increasingly prevalent, especially among the elderly, and can be fatal upon rupture. Currently, there are no effective medications for AAA treatment. To address this, the study employs a comprehensive approach involving genetics, statistics, computer analysis, biology, and mouse models to better understand the genetics and biology of AAA, potentially leading to new treatment strategies.

PI_NAMEs: CHEN, YUQING EUGENE (contact);SURAKKA, IDA LIISA

PROGRAM_OFFICER_NAME: LUO, JAMES

PROJECT_TERMS: abdominal aorta;Abdominal Aortic Aneurysm;Academia;Address;Adverse effects;Affect;Animal Model;Aorta;Apoptosis;Area;ATAC-seq;Atrial Fibrillation;biobank;Bioinformatics;bioinformatics tool;Biological;Biology;Candidate Disease Gene;candidate identification;Cardiovascular Diseases;causal variant;Cause of Death;Cell Culture Techniques;Cell Nucleus;Cells;Cellular biology;Chromatin;Chromosome Mapping;Cleavage Under Targets and Release Using Nuclease;Co-Immunoprecipitations;Collaborations;Complex;Computer Analysis;Coronary Arteriosclerosis;Cytoprotection;Data Set;Development;Diagnosis;Diagnostic;differential expression;Disease;disorder risk;Early Diagnosis;effective therapy;Elastases;Elderly;Etiology;experience;Extracellular Matrix Degradation;Family;follow-up;Follow-Up Studies;Funding;gain of function;gene discovery;Gene Targeting;Genes;Genetic;genetic approach;Genetic Diseases;Genetic study;genetic variant;genome wide association study;genomic locus;Genomic Segment;Genomics;Goals;healthcare burden;Heart;Heritability;High Prevalence;In Vitro;in vivo;Individual;Inflammation;Inosine Dialdehyde;insight;intercellular communication;interest;Knock-in Mouse;Knock-out;Link;loss of function;male;Maps;Medical Research;Mendelian randomization;Meta-Analysis;Methodology;Modeling;mouse model;Multiomic Data;multiple omics;Mus;Myocardial Infarction;novel;novel therapeutic intervention;Operative Surgical Procedures;Organ Donor;Oxidative Stress;Pathogenesis;Pathway interactions;Patient Monitoring;Pharmaceutical Preparations;Pharmacologic Substance;phenome;Play;Population;population based;power analysis;Prevention;Preventive treatment;Probability;Proteins;Publications;Recording of previous events;Regulation;Reporting;Research;response;Rest;Risk;Risk Factors;Role;Rupture;Sample Size;Sampling;Scientist;screening;sex;Sex Differences;single cell ATAC-seq;single-cell RNA sequencing;Smoker;Smooth Muscle Myocytes;statistics;success;Symptoms;TCF7L2 gene;Tissues;tool;trait;transcriptome sequencing;Transgenic Mice;United States;Variant;Vascular Smooth Muscle

PROJECT_TITLE: Using genetics to discover mechanisms of abdominal aortic aneurysm

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


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

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Infections within the brain can cause permanent damage, which makes limiting pathogen growth and spread imperative. We find that caspase-8, a protein that induces cell death, is important for controlling the growth of the parasite Toxoplasma gondii in the brain. The goal of this application is to understand how the brain and immune system limit infection through this cell-death-associated protein.

PI_NAMEs: HARRIS, TAJIE H. (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;adeno-associated viral vector;Apoptosis;Area;Astrocytes;Biological Response Modifiers;Blood - brain barrier anatomy;Brain;brain cell;brain control;Brain region;CASP8 gene;Caspase;Caspase Inhibitor;CD8-Positive T-Lymphocytes;Cell Death;Cell Death Induction;cell type;Cells;Central Nervous System;Central Nervous System Infections;Cessation of life;Chronic Phase;combat;Complex;Confocal Microscopy;Contralateral;Cre lox recombination system;cytokine;Data;Defense Mechanisms;Development;Embryo;Environment;expectation;experimental study;fighting;Genetic;Goals;Growth;Health;Heart;high risk;Human;Immune;Immune response;Immune system;Immunity;Immunocompromised Host;immunoreaction;In Vitro;in vivo;Infection;Infection Control;Interferon Type II;Investigation;Knock-out;Knockout Mice;Label;LoxP-flanked allele;lymph nodes;Macrophage;Measures;Mediating;Mediator;Mus;Neurons;novel;Parasite Control;Parasites;pathogen;Pathology;Pathway interactions;patient population;Patients;perforin;Play;Population;preservation;prevent;Proteins;receptor;Regulation;Reporter;Reporting;Resistance;Role;Stimulus;T-Lymphocyte;Testing;Tissues;TNF gene;TNFRSF1A gene;Toxoplasma gondii;toxoplasmic encephalitis;Toxoplasmosis;Viral;Virus;Visualization;Wild Type Mouse

PROJECT_TITLE: Caspase-8 mediated control of CNS infection

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biomedical Imaging;Breast Cancer;Cancer;Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Social Determinants of Health;Women's Health Research

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

ORG_STATE: MA

PHR: Project Narrative This proposal takes a comprehensive approach to understanding the impact of a wide range of environmental factors including air pollution, and physical stressors (ultraviolet radiation [UV], radon), demographic factors (age, race and ethnicity), and social determinants of health (SDOH) on mammographic features in the Nurses’ Health Study 3. We expect our findings to provide valuable information on the role of modifiable exposures on mammographic features and thus, subsequent breast cancer risk. These findings will inform individual- and population-level prevention, risk assessments, and policy decisions, with the long-term goal of reducing the burden of breast cancer.

PI_NAMEs: LADEN, FRANCINE  (contact);TAMIMI, RULLA M

PROGRAM_OFFICER_NAME: BOYLES, ABEE

PROJECT_TERMS: Address;Age;Air Pollution;Attenuated;Body mass index;Breast Cancer Risk Factor;breast density;Breast Feeding;cancer risk;Characteristics;Chronic stress;cohort;Communities;Complex;Data;deep learning;Demographic Factors;Demographic Impact;deprivation;Diet;Digital Mammography;Economics;Education;Enrollment;Environment;Environmental Exposure;Environmental Risk Factor;Ethnic Origin;experience;Exposure to;Female;follow-up;Future;geographic difference;Goals;Grant;Health;Healthcare;Image;Image Analysis;Individual;Joints;Malignant Breast Neoplasm;Malignant Neoplasms;Mammographic Density;Mammography;Measures;Metabolism;modifiable risk;Neighborhoods;Nurses;Nurses' Health Study;Nursing Students;parity;Participant;Perimenopause;Persons;Physical activity;Policies;Pollution;Population;Positioning Attribute;Postmenopause;Premenopause;Prevention;prospective;Questionnaires;Race;Radon;Recording of previous events;Reporting;Reproductive History;residence;Resources;Risk;Risk Assessment;Risk Factors;Role;social;social determinants;social health determinants;Socioeconomic Status;stressor;Texture;Time;Ultraviolet Rays;Update;uptake;UV Radiation Exposure;Variant;Woman

PROJECT_TITLE: Environmental and social determinants of mammographic features

STUDY_SECTION: SEDH

STUDY_SECTION_NAME: Social and Environmental Determinants of Health Study Section[SEDH]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biotechnology;Facioscapulohumeral Muscular Dystrophy;Genetics;Muscular Dystrophy;Orphan Drug;Rare Diseases

ORG_CITY: Aurora

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Misexpression of an early embryonic transcription factor, DUX4, in the skeletal muscle causes facioscapulohumeral muscular dystrophy (FSHD) through poorly understood mechanisms. This proposal aims to fill a critical gap in our knowledge of DUX4 pathobiology by investigating the mechanisms of misregulated RNA processing and quality control induced by DUX4. Our findings will pave the way to identify new therapeutic vulnerabilities for FSHD and other neuromuscular diseases caused by perturbed RNA metabolism.

PI_NAMEs: JAGANNATHAN, SUJATHA  (contact)

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: Address;Affect;Arginine;Binding Sites;Biochemistry;Biological Assay;Bromouridine sequencing;Cell Culture Techniques;Cell Death;Cells;Cellular Stress;crosslinking and immunoprecipitation sequencing;Embryo;experimental study;Facioscapulohumeral Muscular Dystrophy;Failure;Gene Expression;gene regulatory network;Genes;Genetic Diseases;Genetic Transcription;Genome engineering;Genomics;Goals;homeodomain;Human;knock-down;Knowledge;Label;Lead;Mass Spectrum Analysis;Measures;Mediating;Metabolism;Modeling;mRNA Precursor;multicatalytic endopeptidase complex;Muscle Cells;Mutation;Myopathy;Neuromuscular Diseases;novel;novel therapeutics;overexpression;Pathogenicity;Pathway interactions;Pattern;Point Mutation;Post-Transcriptional Regulation;posttranscriptional;Production;Protein Isoforms;Protein Truncation;Proteins;Proteome;Proteomics;Quality Control;Regulation;Reporter;Research;Research Proposals;RNA;RNA chemical synthesis;RNA Decay;RNA metabolism;RNA Processing;RNA Splicing;Role;Serine;Skeletal Muscle;System;Testing;Time;Toxic effect;Transcript;transcription factor;Translating;Ubiquitin;Up-Regulation;Work

PROJECT_TITLE: Mechanisms of DUX4-induced misregulation of RNA processing and quality control

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Prostate Cancer;Urologic Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: SURGERY

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Narrative Men with Castration-resistant Prostate Cancer (CRPC) do not respond to standard of care therapies or immunotherapy. To address this shortcoming, we developed a first-in-class ACK1 inhibitor, (R)-9b which not only suppressed AR/AR-V7 within the CRPCs tumors, but also activated the host immune response against tumors. The (R)-9b compound has shown good safety profiles in mouse, rat and canine models. This proposal is directed towards running the first-in-man Phase I clinical trial for (R)- 9b in CRPC patients. We will evaluate the safety, efficacy, tolerability and PSA levels in CRPC patients treated with (R)-9b. A successful Phase I trial should pave the way to Phase II/III clinical trials.

PI_NAMEs: MAHAJAN, KIRAN ;MAHAJAN, NUPAM P (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: 3-Dimensional;abiraterone;ACK1 Gene;acronyms;Address;advanced prostate cancer;American;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Animal Model;Animals;antagonist;anti-tumor immune response;Antitumor Response;Autopsy;Biological Assay;Blood specimen;Brain;Cancer Etiology;Cancer Patient;canine model;Canis familiaris;capsule;CD8-Positive T-Lymphocytes;Cessation of life;Clinical Research;Clinical Trials;cytotoxic;Data;Development;Disease;Dose;Drug Kinetics;enzalutamide;Epigenetic Process;Evaluation;Exhibits;first-in-human;G-Protein-Coupled Receptors;Gastrointestinal tract structure;Generations;Goals;Guidelines;Heart;Hepatocyte;Histology;Human;Immune;immune activation;immune checkpoint blockade;Immune response;Immune system;Immunocompetent;immunoregulation;Immunotherapy;inhibitor;innovation;Investigation;Investigational Drugs;Ion Channel;kinase inhibitor;Knockout Mice;Liver;Malignant neoplasm of prostate;Malignant Neoplasms;Maximum Tolerated Dose;men;Mesylates;metabolic abnormality assessment;Metabolism;Modality;mouse model;Mus;novel;novel therapeutics;Nuclear Receptors;Oral Administration;Organ;Organoids;Pathologist;Patients;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;Permeability;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Phase;Phase I Clinical Trials;phase I trial;Phase II Clinical Trials;phase II trial;Phase II/III Clinical Trial;Phosphotransferases;Property;Prostate;Prostate-Specific Antigen;Prostatic Neoplasms;Protein Tyrosine Kinase;PSA level;radiological imaging;Rattus;Recommendation;Recurrence;Recurrent disease;Refractory;Resistance;Resistance development;restraint;Rodent Model;Running;Safety;safety assessment;Serology;small molecule;small molecule inhibitor;Sodium Chloride;Solubility;Specificity;standard of care;T-Cell Activation;targeted treatment;Testing;Therapeutic;Tissue Sample;Tissues;Toxic effect;Toxicology;translational study;tumor;tumor growth;tumor microenvironment;Tumor Tissue;tumor xenograft;tumor-immune system interactions;United States Food and Drug Administration;virtual;Weight Gain

PROJECT_TITLE: Phase 1 First in Human Trial to Assess Safety and Tolerability of the Novel ACK1 Inhibitor (R)-9b in Patients with Prostate Cancer

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: The proposed research is relevant to public health because it will have a positive impact on developing new approaches to enhance healthspan in older adults. Specifically, this project will provide new fundamental knowledge of how the inflammatory secretome of adipose tissue influences key functional and physiological parameters in skeletal muscle, particularly the molecular response to exercise. The project is relevant to the mission of NIA because it satisfies a critical need for understanding factors that contribute to skeletal muscle dysfunction with aging.

PI_NAMEs: LANZA, IAN R (contact)

PROGRAM_OFFICER_NAME: BOYCE, AMANDA T

PROJECT_TERMS: Abdomen;Acute;Adipose tissue;Aging;Anatomy;Attenuated;Biology;candidate identification;Cells;Chemicals;Chronic;Clinical Research;Controlled Environment;Data;design;Development;Endocrine;Exercise;Exercise Physiology;Exhibits;experimental study;Exposure to;frailty;Functional disorder;Gene Expression;gerotherapeutic;Health;healthspan;Histology;Human;Image;Immunohistochemistry;Impairment;In Vitro;in vivo;in vivo imaging;Individual;Inflammation;Inflammatory;inhibitor;Inpatients;insight;interdisciplinary approach;Knowledge;Link;Measurement;Messenger RNA;Metabolic;mimetics;Mission;mitochondrial dysfunction;Molecular;molecular phenotype;Molecular Profiling;Muscle;Muscle Cells;Muscle Fibers;Muscle function;muscle physiology;Muscle Proteins;novel strategies;Obesity;older adult;older men;paracrine;Pathway interactions;Persons;Phenotype;Physiological;Protein Biosynthesis;protein expression;Proteomics;Public Health;Research;Resistance;response;Role;sarcopenia;Serum;Signal Pathway;Signal Transduction;Signaling Protein;Skeletal Muscle;Source;Tissues;transcriptomics;translational study;Woman;Work;young adult;young man

PROJECT_TITLE: Mechanisms of Anabolic Resistance in Older Humans

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Bioengineering;Congenital Structural Anomalies;Pediatric;Physical Activity;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PHILADELPHIA

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative This US-Ireland Research and Development (R&D) Partnership Programme project aims to determine the effects of maternal exercise on fetal akinesia-impaired skeletal development and to define the cellular and molecular mechanisms.

PI_NAMEs: BOERCKEL, JOEL D (contact);DYMENT, NATHANIEL A.

PROGRAM_OFFICER_NAME: ILEKIS, JOHN V

PROJECT_TERMS: 3-Dimensional;Amniotic Fluid;Arthrogryposis;Bioreactors;bone;Bone Development;Cartilage;cell type;Cells;Connective Tissue;Data;Defect;Development;Dysplasia;Embryo;Exercise;Exercise Physiology;Exhibits;fetal;Fetal Movement;Fetal Skeleton;GDF5 gene;Genetic;Genetic Transcription;Goals;Hip region structure;Human;Image;Impairment;in vivo;innovation;insight;International;Intervention;Ireland;Joints;KITLG gene;Knock-out;Ligaments;Limb Development;Limb structure;mechanical force;mechanical load;mechanical signal;Mechanical Stimulation;mechanotransduction;Mediating;Meniscus structure of joint;Modeling;Molecular;Morphogenesis;morphometry;Movement;Mus;Muscle Contraction;Muscle Development;muscle progenitor cell;Mutation;novel strategies;Osteoblasts;Osteogenesis;osteoprogenitor cell;Patients;Perinatal mortality demographics;pharmacologic;Phenotype;Population;Positioning Attribute;progenitor;programs;research and development;response;Role;Running;Signal Transduction;single-cell RNA sequencing;skeletal;Skeletal Development;skeletal disorder;Skeletal Muscle;skeletal stem cell;Techniques;Tendon structure;Testing;Therapeutic;Therapeutic Intervention;tissue stem cells;Tissues;Transcriptional Regulation

PROJECT_TITLE: Effects of maternal exercise on fetal akinesia-impaired bone and joint development

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: LOS ANGELES

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

PHR: PROJECT NARRATIVE. Fear of trauma-associated stimuli even after they have ceased to be threats is a core pathology of Post-Traumatic Stress Disorder (PTSD) that results from being unable to learn that stimuli previously linked to trauma are no longer dangerous (deficits in extinction learning). Of relevance to the Strategic Objectives #1 and #3 of NIMH’s mission which are to “define mechanisms of complex behaviors while striving for preventions and cures”, our proposal will shed light on how molecular mechanisms in sub- thalamic neurons influence extinction learning. The proposed research is relevant to public health because our results will provide a foundation from which future studies could identify core pathways underlying extinction learning across the entire brain, eventually resulting in new pharmacotherapies to reduce the burden of maladaptive fear associated with PTSD.

PI_NAMEs: DIAS, BRIAN GEORGE (contact)

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Affect;Auditory;Behavior;Brain;Brain region;Cell Physiology;Cells;Clinical;Cognitive Therapy;Communication;Complex;conditioned fear;CREB1 gene;Cues;Dangerousness;Dimensions;Dopamine;Dopaminergic Cell;experience;Extinction;fear memory;Foundations;Fright;Functional disorder;Future;Genetic;Glucocorticoid Receptor;Glucocorticoids;Goals;Impairment;knock-down;Knock-out;Knowledge;Learning;learning extinction;Link;Measures;Mediating;Memory;midbrain central gray substance;Mission;Molecular;Molecular Genetics;Mus;mutant;National Institute of Mental Health;Nervous System;neural circuit;Neurobiology;Neuromodulator;Neurons;optogenetics;Pathology;Pathway interactions;Pharmacotherapy;Physiological;Play;Post-Traumatic Stress Disorders;Prevention;Process;Proteins;Protocols documentation;Public Health;Quality of life;receptor expression;recruit;Research;Retrieval;Reuniens Thalamic Nucleus;RNA Interference;Role;self-directed learning;Signal Transduction;Stimulus;Stress;Testing;Time;Training;Trauma;Ventral Tegmental Area;Work;zona incerta

PROJECT_TITLE: Molecular mechanisms underlying sub-thalamic influences on extinction learning

STUDY_SECTION: BRLE

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


NIH_SPENDING_CATS: Genetics

PHR: The proposed research is relevant to public health, because this work aims to illuminate the diverse and dynamic mechanisms of RNA regulation in gene expression as well as how this regulation is impacted by disease. As such, the proposed research is relevant to the part of the NIH's mission that seeks to develop fundamental knowledge to inform our diagnosis and treatment of human disease.

PI_NAMEs: SIMON, MATTHEW DAVID (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: Acute Megakaryocytic Leukemias;analog;analysis pipeline;Antisense Oligonucleotides;Awareness;biological systems;Biology;Blood Cells;Cell Cycle;Cells;Chemistry;Chimeric Proteins;Code;Complementary DNA;Computer software;Data;Detection;Development;Diagnosis;Dimensions;Disease;End Point Assay;experimental study;EZH2 gene;flexibility;Gene Expression;Gene Expression Regulation;Genetic Transcription;genomic locus;Grant;human disease;improved;innovation;insight;Kinetics;Knowledge;Label;Life Cycle Stages;Measures;Metabolic;Metabolism;Methods;Mission;Modality;Modeling;Neonatal;Nonsense-Mediated Decay;Nucleotides;open source;Parameter Estimation;Pattern;Population;Positioning Attribute;Production;promoter;Protein Isoforms;Protocols documentation;Public Health;Regulation;Research;Resolution;response;RNA;RNA analysis;RNA chemical synthesis;RNA Degradation;RNA metabolism;RNA Polymerase II;RNA Processing;RNA Splicing;sequencing platform;Site;small molecule;Techniques;Technology;Therapeutic;Thiouridine;Transcript;Transcription Initiation;transcriptome sequencing;United States National Institutes of Health;Work

PROJECT_TITLE: Revealing the dynamics of RNA metabolism with nucleotide recoding chemistry

STUDY_SECTION: GCAT

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


NIH_SPENDING_CATS: Aging;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Neurosciences;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Narrative We propose to continue the Undiagnosed Diseases Network Miami Clinical Site to evaluate and provide data from over 40 participants annually with various undiagnosed conditions. A major focus will be on enrolling underrepresented minority groups into UDN – an area UDN Miami has been a leader in the current funding cycle. Our team’s combined expertise in genetics and genomics, sensory disorders, robust biorepositories, outreach and ethics ensures the success of this proposal.

PI_NAMEs: TEKIN, MUSTAFA  (contact);ZUCHNER, STEPHAN

PROGRAM_OFFICER_NAME: DOSS, ARGENIA LANISHA NECOLE

PROJECT_TERMS: Address;Affect;African American;African American population;Area;Artificial Intelligence;biobank;Bioinformatics;Black race;Candidate Disease Gene;Caribbean region;causal variant;Central America;Clinic;Clinical;clinical research site;Code;cohort;Collaborations;Communities;cultural competence;Data;data sharing;Diagnosis;Diagnostic;Disease;disparity reduction;DNA;Education;Enrollment;Ensure;Environmental Exposure;Ethics;ethnic diversity;ethnic minority;Etiology;Evaluation;Evaluation Research;Eye;Face;Feedback;Florida;Foundations;Funding;gene environment interaction;Genes;Genetic;genome sequencing;Genomics;Goals;Health;health disparity;health equity;health equity promotion;Health system;Hearing;hearing impairment;hereditary neuropathy;Hispanic;Hispanic Americans;Hospitals;improved;In Vitro;Individual;innovation;International;Investigation;Latino Population;Linguistics;Medical;medical schools;metabolomics;Methodology;Minority;Minority Enrollment;Minority Groups;Minority Participation;model organism;Molecular;Mosaicism;Neighborhood Health Center;non-genetic;non-genomic;novel;Outcome;outreach;Participant;participant enrollment;patient engagement;Patients;Peripheral Nerves;Persons;Phenotype;Pilot Projects;Population;Process;programs;Quality of Care;racial diversity;racial minority;Rare Diseases;recruit;Recruitment Activity;Research;Resources;Science;Sensory;Sensory Disorders;sensory system;Services;Short Tandem Repeat;Site;social health determinants;Societies;South America;Structural defect;success;Surveys;telehealth;tool;transcriptome sequencing;Underinsured;Underrepresented Minority;Underrepresented Populations;Underserved Population;Uninsured;United States National Institutes of Health;Universities;Untranslated RNA;Variant;Vision;Work

PROJECT_TITLE: The Undiagnosed Diseases Network Clinical Site of Miami

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-W (21)]


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Precision Medicine;Prevention;Psychosis;Schizophrenia;Serious Mental Illness;Suicide

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

PHR: PROJECT NARRATIVE A first episode of psychosis is a leading cause of disability in young adults, with high risk of suicide and all cause mortality. A substantial part of the burden and cost relates to poor functional outcomes, and the inability to determine the right antipsychotic treatment during the earliest phases of psychotic illness, particularly for those who might need clozapine, a medication that is already known to work best for those who do not respond to conventional antipsychotics. In patients with a first episode of psychosis, the present study aims to determine whether the use of biomarker guided treatment decisions leads to better outcomes and equivalent side effects in people prescribed clozapine compared to conventional antipsychotics, including changes in brain function.

PI_NAMEs: LAHTI, ADRIENNE C (contact)

PROGRAM_OFFICER_NAME: RUDORFER, MATTHEW V

PROJECT_TERMS: Acceleration;acute care;Adherence;Adolescence;Age;aged;Agranulocytosis;Antipsychotic Agents;aripiprazole;Biological Markers;blind;Brain;Brain scan;Caring;Clinical;Clozapine;cohort;Complex;Controlled Study;Corpus striatum structure;cost;Country;critical developmental period;critical period;Data;Decision Making;Dedications;Development;disability;dissemination strategy;Dose;early psychosis;Education;efficacy evaluation;efficacy trial;Elements;emerging adult;Employment;expectation;experience;Failure;Family;Family member;Feeling suicidal;first episode psychosis;Functional Magnetic Resonance Imaging;functional MRI scan;functional outcomes;Future;General Population;genetic testing;genomic locus;Genotype;Goals;high risk;HLA-DQB1;Hospitalization;Hospitals;Image;implementation science;improved;improved outcome;indexing;Individual;inpatient service;Lifelong disability;Lived experience;Magnetic Resonance Imaging;Melanocortin 4 Receptor;mortality;National Institute of Mental Health;Neutropenia;Outcome;Patient-Focused Outcomes;Patients;Pattern;Persons;Pharmaceutical Preparations;Pharmacogenetics;Phase;Population;Precision therapeutics;predicting response;predictive marker;preservation;primary outcome;Psychiatry;Psychoses;psychotic;Psychotic Disorders;Publishing;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Receptor Gene;reducing suicide;Research Design;Resistance;responders and non-responders;response;Rest;Risk;risk variant;Risperidone;Schizophrenia;secondary outcome;Services;side effect;specific biomarkers;Subgroup;suicidal morbidity;suicidal risk;support tools;Symptoms;System;Testing;Therapeutic;tool;treatment response;trial comparing;Weight;Weight Gain;Work;young adult;Youth

PROJECT_TITLE: 4/5 Biomarkers to Enhance Early Schizophrenia Treatment (BEEST)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-S (60)]


NIH_SPENDING_CATS: Cardiovascular;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Heart Disease;Hypertension;Liver Disease;Organ Transplantation;Prevention;Transplantation

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE One in three liver transplant recipients experiences a cardiovascular event after transplant because of immunosuppression medications and a high prevalence of cardiovascular risk factors, such as high blood pressure. This study uses novel statistical methods applied to prospectively collected observational data to identify the best treatment approaches for high blood pressure in liver transplant recipients that reduce cardiovascular risk without doing harm to other organs. Improving the outcome of each liver transplant patient is of paramount importance to society due to the organ shortage and the enormous resources that are invested into transplanting each patient.

PI_NAMEs: VANWAGNER, LISA B (contact)

PROGRAM_OFFICER_NAME: ANAYA, GABRIEL

PROJECT_TERMS: Address;Affect;Angiotensin Receptor;Angiotensin-Converting Enzyme Inhibitors;Biological Markers;biomarker identification;Blood Pressure;blood pressure control;blood pressure elevation;blood pressure reduction;Brain;Brain Injuries;Brain natriuretic peptide;Calcium Channel Blockers;Cardiac;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular risk factor;Cardiovascular system;Cirrhosis;Clinical;clinical practice;Clinical Practice Guideline;cognitive function;Cohort Studies;Data;design;Event;evidence base;evidence based guidelines;experience;Future;General Population;Geographic Locations;Goals;graft function;Harm Reduction;High Prevalence;high risk;Home;Hybrids;Hypertension;hypertension control;hypertension treatment;Immunosuppression;improved;improved outcome;Individual;Infrastructure;Injury to Kidney;Intervention Trial;Investments;Kidney;Knowledge;Liver;liver function;liver transplantation;Measures;modifiable risk;Morbidity - disease rate;mortality;mortality risk;multidisciplinary;myocardial injury;N-terminal;novel;optimal treatments;Organ;Outcome;Participant;Pathogenesis;patient population;Patients;Peripheral Resistance;personalized approach;Pharmaceutical Preparations;Population;post-transplant;precision medicine;prospective;Randomized;Recommendation;Renal function;Renin-Angiotensin-Aldosterone System;Research Personnel;Resources;Retrospective Studies;Risk;Risk Factors;Role;Societies;Statistical Methods;Stratification;Stress;Subgroup;Surveys;Techniques;Testing;thiazide;transplant centers;Transplant Recipients;Transplantation;Troponin T;Variant

PROJECT_TITLE: Avoiding Cardiovascular Complications in Liver Transplantation through Novel Studies (ACCT NOW) in Hypertension

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


ED_INST_TYPE: SCHOOLS OF EDUCATION

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Pediatric;Social Determinants of Health;Substance Misuse;Women's Health Research

ORG_CITY: EUGENE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: 8. Project Narrative Pregnant, postpartum, and parenting people (parents) represent the majority of people with substance use disorders (SUD), yet their unique needs and intersectional experiences are often overlooked in research as it relates to supporting treatment engagement. The goal of the proposed study is to establish a patient engagement research center focused on parents with SUD, by leveraging a lived experience advisory panel (N = 18), special emphasis panels, and a Data Collective of 1,150 parents with SUD to serve as a national resource for other researchers seeking to facilitate treatment engagement among this population. Our approach emphasizes shared power and decision-making and a consideration of intersectional experiences of discrimination (e.g., race, ethnicity, gender, class, parenting status, rurality) to support innovative and transformative research to facilitate treatment engagement and success among parents with SUD.

PI_NAMEs: CIOFFI, CAMILLE C (contact);LEVE, LESLIE DIANE

PROGRAM_OFFICER_NAME: FITZ-RANDOLPH, MARCY ESTHER

PROJECT_TERMS: 6 year old;Address;Area;Attention;barrier to care;Benchmarking;Birth;Caring;Child;Child Care;Child Rearing;Clinic;Collaborations;Communities;community based participatory research;Consultations;Data;Databases;Decision Making;Dedications;Discrimination;disenfranchised population;Disparity;Documentation;effectiveness research;Ethnic Origin;Evaluation;Excision;experience;Face;Family;Feeling hopeless;Fright;Future;Gender;Goals;Grief reaction;improved;improved outcome;Individual;Infant;Infrastructure;innovation;internalized stigma;Lead;Life;Lived experience;member;Modeling;Mothers;Motivation;National Institute of Drug Abuse;Opioid;Outcome;parental role;Parents;Participant;patient engagement;perceived discrimination;Perception;person centered;Persons;Pilot Projects;Population;Postpartum Period;Pregnancy;pregnant;Procedures;Process;programs;Race;Recovery;recruit;Reporting;Research;research data dissemination;Research Design;Research Ethics;Research Methodology;Research Personnel;Research Priority;Research Project Grants;research study;Resources;return to use;rurality;Safety;Science;Shame;social health determinants;social stigma;Substance Use Disorder;substance use treatment;success;sustained recovery;Training;Translational Research;treatment disparity;Treatment outcome;treatment services;willingness;Work

PROJECT_TITLE: A Patient Engagement Resource Center using Community-Based Participatory Action Research to Support Parents with Substance Use Disorders

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 SAI-E (M1)]


NIH_SPENDING_CATS: Bioengineering;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Our proposed VCEUD (Vanderbilt Center of Excellence in Undiagnosed Diseases) will function in the broader Undiagnosed Disease Network to identify the cause of undiagnosed diseases and thus help patients and their families. We will work with local communities and organizations to increase the recruitment of underserved and minority patients into UDN. We will also work with UDN to develop more powerful AI-based tools and resources to make diagnosing undiagnosed diseases more efficient and to help doctors find people with undiagnosed conditions more easily.

PI_NAMEs: BASTARACHE, LISA ;CASSINI, THOMAS ANTHONY;COGAN, JOY D;HAMID, RIZWAN  (contact);PHILLIPS III, JOHN ATLAS

PROJECT_TERMS: Artificial Intelligence;Awareness;Bioinformatics;Caring;Classification;Clinical;Clinical effectiveness;Communities;community engagement;community organizations;community partners;Data Analyses;Data Coordinating Center;Database Management Systems;Development;Diagnosis;Diagnostic;Diagnostic Procedure;Diagnostic tests;Differential Diagnosis;Disease;DNA Databases;Endocrinologist;Environmental Exposure;Etiology;Evaluation;exhaust;Family;Funding;Generations;Genes;Genetic;genomic data;Genomics;Goals;health disparity;Human;Immunologist;improved;Individual;innovation;Institution;Internist;large language model;machine learning algorithm;Medical Records;Methodology;Methods;Minority Groups;minority patient;multiple omics;National Institute of Neurological Disorders and Stroke;Natural Language Processing;Neurologist;new technology;next generation;non-genetic;novel;novel strategies;Ontology;outreach;patient population;Patients;pediatrician;Persons;phenomics;Phenotype;Physicians;Population;programs;Psychologist;recruit;Research;research clinical testing;Resources;rheumatologist;Site;Specialist;Stream;structural biology;Symptoms;Test Result;Testing;Time;tool;Training and Education;Underserved Population;United States National Institutes of Health;Validation;Variant;Work

PROJECT_TITLE: Vanderbilt Center of Excellence for Undiagnosed Disease (VCEUD)


ORG_CITY: HOUSTON

ORG_DEPT: PEDIATRICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Strategies disrupting MYCN oncogenic programs are critically needed for neuroblastoma therapy. High-risk, MYCN-amplified neuroblastoma is characterized by high relapse and mortality rates, dysregulated tumor metabolism, and an immune-suppressive tumor microenvironment. As the development of effective immunotherapies requires new definitions of the negative regulations impairing an adequate immune response, our proposed research will provide a novel view on how oncogenic MYCN reprograms the metabolic environment of NB to drive immune evasion. Our proposed research will also aim at modulating the metabolic environment of neuroblastoma to enhance immune-based approaches for high-risk MYCN-amplified disease.

PI_NAMEs: BARBIERI, EVELINE  (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: Adoptive Cell Transfers;Anabolism;Antibodies;Antitumor Response;Automobile Driving;Biology;Cell Physiology;Cells;Cellular Metabolic Process;Chemicals;chemotherapy;Child;chimeric antigen receptor T cells;Coculture Techniques;Complex;Consumption;Cysteine;Cysteine Metabolism Pathway;Data;Death Rate;Dependence;Development;Disease;Disease remission;disorder risk;Energy-Generating Resources;Environment;Enzymes;Essential Amino Acids;exhaustion;extracellular;Functional disorder;Genetic;Goals;Growth;high risk;Homeostasis;Human;Immune;immune cell infiltrate;immune checkpoint blockade;Immune Evasion;Immune response;Immunocompetent;Immunologics;immunomodulatory therapies;Immunosuppression;Immunotherapy;Impairment;improved;Interferons;Literature;Malignant Childhood Neoplasm;Malignant Neoplasms;Memory;Metabolic;metabolic engineering;Metabolism;metabolomics;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Mutation;MYCN gene;Neoadjuvant Therapy;neoplastic cell;Neural Crest;Neuroblastoma;No Evidence of Disease;novel;Nutrient;Oncogenes;Oncogenic;Operative Surgical Procedures;Oxidation-Reduction;Pathway interactions;Patients;pharmacologic;Phenotype;Process;programs;Progressive Disease;Radiation;recruit;Regulation;Relapse;Research;Role;Signal Transduction;Starvation;stem cells;Supplementation;Survival Rate;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Therapeutic Intervention;therapy resistant;transcriptomics;Tretinoin;tumor;tumor immunology;tumor metabolism;tumor microenvironment;tumorigenesis;Withholding Treatment

PROJECT_TITLE: Rewired Metabolism and Immunosuppression in MYCN-driven Neuroblastoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BTC-Q (80)]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Infectious Diseases;Rare Diseases

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Narrative  Human cytomegalovirus infects almost everyone, causes birth defects and disease in people sick with cancer, AIDS, and those undergoing organ transplants, exacerbates cardiovascular diseases, and modulates human glioblastoma multiforme brain tumors. This work will study how HCMV establishes lifelong infection of humans.

PI_NAMEs: KALEJTA, ROBERT F (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Alleles;Award;Brain Glioblastoma;Brain Neoplasms;Cardiovascular Diseases;CD34 gene;Cells;Clinical;Complex;Congenital Abnormality;CREB1 gene;Cytomegalovirus;Disease;Endothelial Cells;Epithelial Cells;experimental study;Fibroblasts;Funding;Genetic Transcription;Glycoproteins;Human;Infection;Laboratories;latent infection;Lytic;Lytic Phase;Malignant Neoplasms;Mediating;member;MIEP;NF-kappa B;Organ Transplantation;Outcome;Pathway interactions;Persons;Phosphorylation;prevent;Proteins;Receptor Signaling;Repression;Role;STAT3 gene;Stimulator of Interferon Genes;TBK1 gene;Testing;Transcriptional Regulation;Tropism;Viral;Virion;Virus;Work

PROJECT_TITLE: Transcriptional Control of Human Cytomegalovirus Latency

STUDY_SECTION: VDT

STUDY_SECTION_NAME: Viral Dynamics and Transmission Study Section [VDT]


NIH_SPENDING_CATS: Aging;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Nutrition;Physical Activity;Prevention

ORG_CITY: LOUISVILLE

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: PROJECT NARRATIVE Advanced age is the leading risk factor for all chronic diseases. Although many hallmarks of aging have been identified, a key physiological feature of aging is decreased blood flow and an inability to match blood flow to organ requirements. This project will elucidate the metabolic mechanisms by which aging impairs blood flow in the heart and identify interventions to improve blood flow, heart function, and exercise tolerance over the lifespan.

PI_NAMEs: HILL, BRADFORD GUY (contact);NYSTORIAK, MATTHEW A

PROGRAM_OFFICER_NAME: GAO, HONGWEI

PROJECT_TERMS: active lifestyle;Acute;Affect;age effect;age related;age related changes;age related decline;age-related disease;aged;Aging;Atherosclerosis;Attenuated;Blood flow;Blood Vessels;carbohydrate metabolism;Carbohydrates;Cardiac;cardiac aging;Cardiac Myocytes;Cardiac Output;cardiovascular health;Cardiovascular Physiology;Catabolism;Chronic;Chronic Disease;Clinical;Contrast Echocardiography;Coronary;coronary perfusion;Coupling;Data;Defect;Dementia;Diabetes Mellitus;efficacy evaluation;Elderly;Etiology;Exercise;exercise capacity;exercise intolerance;Exercise Tolerance;Failure;fatty acid metabolism;Fatty Acids;flexibility;Functional disorder;Genetic;Genetic Models;Glucose;glucose metabolism;hallmarks of aging;Heart;heart function;heart metabolism;Hyperemia;hypoperfusion;Immunologics;Impairment;improved;In Vitro;in vivo;Infusion procedures;insight;Intervention;Ketone Bodies;Knowledge;Left Ventricular Function;life span;Link;Longevity;Measures;Metabolic;metabolic profile;Metabolism;Modeling;mortality risk;Mus;Myocardial;Myocardial perfusion;NADH;novel strategies;old mice;Organ;oxidation;Oxidation-Reduction;Oxygen;paracrine;pathological aging;Perfusion;Peripheral;Physical activity;Physiological;Play;preservation;pressure;prevent;Pump;pyridine nucleotide;Radiolabeled;Regulation;response;restoration;Risk Factors;Role;sex;Signal Transduction;Smooth Muscle;Smooth Muscle Myocytes;stable isotope;Stress;Structure;Testing;Tissues;Vascular Smooth Muscle;Vasodilation;voltage;Work;Workload

PROJECT_TITLE: Metabolic regulation of myocardial perfusion in the aging heart

STUDY_SECTION: MPPA

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


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Serious Mental Illness;Social Determinants of Health

ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE Maternal depression is a robust predictor of internalizing symptoms and disorders in offspring, highlighting the public health importance of studying causal risk mechanisms early in development to inform targeted prevention efforts at the earliest possible point. The current project combines behavioral and neural measures across 3 time points spanning ages 4 to 8 years to examine how developmental trajectories of reward responsiveness shape early internalizing symptoms among offspring of depressed mothers. By examining how maternal positive emotion behaviors and child early life adversity impact these pathways, findings from the current study have significant potential to inform novel prevention targets for specific populations of at-risk youth.

PI_NAMEs: BURKHOUSE, KATIE L (contact);KUJAWA, AUTUMN J

PROGRAM_OFFICER_NAME: KING, ERIN MICHELE

PROJECT_TERMS: 6 year old;Acceleration;Address;Adolescence;Adolescent;Affect;Age;Anxiety;Anxiety Disorders;Area;Automobile Driving;Behavior;Behavioral;Biological;Brain;Buffers;Child;Child Development;Child Rearing;Childhood;Clinical;Communities;Data;Depressed mood;Depressive disorder;deprivation;design;Development;Disease;early childhood;early life adversity;Electroencephalography;Emotional;emotional neglect;Emotions;Enrollment;Environment;Environmental Risk Factor;Event-Related Potentials;Exhibits;experience;Exposure to;Foundations;Future;high risk;Impairment;Individual;infancy;innovation;Intercept;intergenerational;Intervention;Life;longitudinal design;maternal depression;Measures;Mental Depression;Methods;metropolitan;middle childhood;Mothers;multimodality;National Institute of Mental Health;Neighborhoods;neural;novel;Nursery Schools;offspring;Parents;Pathway interactions;Patient Self-Report;Pattern;physical neglect;Pilot Projects;Populations at Risk;positive emotional state;Positive Valence;Predictive Value;Prevention;Process;prospective;protective factors;Psychopathology;Public Health;Recording of previous events;recruit;Reporting;Research;Research Design;Research Domain Criteria;Rewards;Risk;Risk Factors;Risk Marker;Role;Sampling;School-Age Population;Shapes;Site;social;Socialization;socialization behavior;Symptoms;System;Systems Development;Testing;theories;Time;Translating;Work;Youth

PROJECT_TITLE: Charting Positive Valence Systems Trajectories in Offspring of Depressed Mothers to Predict Internalizing Symptoms in Early Childhood

STUDY_SECTION: PDRP

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


ORG_CITY: SAN FRANCISCO

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health as it addresses the fundamental question of how suppression of an enzyme involved in exosome biogenesis may provide a novel means of reactivating that anti-tumor immune response. New knowledge gained through this application is expected to lead to novel therapeutic strategies that have the potential to overcome resistance to current immune therapies. Therefore, the research is relevant to NIH’s mission to foster fundamental creative discoveries that increase the nation's capacity to protect and improve human health.

PI_NAMEs: BLELLOCH, ROBERT  (contact);RAIS, RANA ;SLUSHER, BARBARA STAUCH

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: 4T1;Address;Adult;Allogenic;analog;analytical tool;anti-tumor immune response;aqueous;Binding Proteins;Biogenesis;Biological Availability;cancer cell;Cancer Model;cancer therapy;cancer type;Canis familiaris;Carbamates;cell killing;Cells;chemical stability;Clinical;clinical translation;Clinical Trials;Creativeness;CT26;Data;Development;Dose;Drug Kinetics;Effectiveness;effectiveness evaluation;efficacy evaluation;efficacy study;Enzymes;Exhibits;exosome;Fostering;Future;Genetic;Goals;Growth;Health;high throughput screening;Human;human cancer mouse model;human model;humanized mouse;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;immunodeficiency;Immunooncology;Immunosuppression;Immunotherapy;improved;In Vitro;in vitro testing;in vivo;inhibitor;Interleukin-15;Knock-out;Knowledge;Lead;Liver;Malignant Neoplasms;Mass Spectrum Analysis;MC38;Measures;meetings;Metabolic;Mission;Modeling;Molecular;mouse model;Mus;nanomolar;novel;novel therapeutic intervention;Oral;Patients;Peptide/MHC Complex;Permeability;Pharmaceutical Preparations;Phenotype;Plasma;pre-clinical;Primates;Prodrugs;Production;programmed cell death ligand 1;Property;Public Health;public health relevance;Rattus;refractory cancer;Research;Resistance;response;Safety;scaffold;small molecule;Solubility;Specific qualifier value;Structure-Activity Relationship;T-Lymphocyte;Testing;Therapeutic;Time;Toxic effect;Translations;Transplantation;tumor;Tumor Cell Line;tumor growth;Tumor Immunity;tumor progression;Tumor Suppression;Tumor-Derived;United States National Institutes of Health;Xenograft procedure

PROJECT_TITLE: Evaluating and Optimizing Novel nSMase2 Inhibitors in the Treatment of Cancers

STUDY_SECTION: DMPC

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


NIH_SPENDING_CATS: Cachexia;Cancer;Kidney Disease;Nutrition;Ovarian Cancer;Rare Diseases;Women's Health Research

PHR: Project Narrative Skeletal muscle wasting is a dread complication of chronic kidney disease that increases morbidity and mortality. We have evidence that CRL4ACRBN E3 ubiquitin ligase promotes muscle wasting. Pharmacological inhibition of this enzyme, through repurposing of the pomalidomide could prevent muscle wasting in chronic kidney disease.

PI_NAMEs: HU, ZHAOYONG  (contact)

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: Acceleration;Address;Affect;Affinity Chromatography;Angiotensin II;Binding;CASP3 gene;Cell Culture Techniques;Chronic;Chronic Kidney Failure;combat;Complication;cost effective;Coupled;cullin 4A;Cullin Proteins;cytokine;Development;Disease;DNA Damage;Down-Regulation;drug repurposing;Enzyme Inhibition;Equilibrium;FBXO32 gene;FDA approved;Genes;Glucocorticoids;Goals;Homeostasis;Human;humanized mouse;immune modulating agents;Immunomodulators;Inflammation;inhibitor;Insulin Resistance;Intervention;Investigation;Kidney;Knock-out;Ligase;Mass Spectrum Analysis;Mediating;Mediator;Metabolic acidosis;Metabolism;Methods;Mitochondria;mitochondrial dysfunction;Morbidity - disease rate;mortality;mouse model;multicatalytic endopeptidase complex;multiple omics;Mus;Muscle;Muscle Fibers;Muscle Proteins;muscle RING finger 1;muscle stress;Muscular Atrophy;Myopathy;NF-kappa B;novel;novel therapeutics;nutrition;ovarian neoplasm;Oxidative Stress;Pathogenesis;Pathway interactions;Patient Care;Patients;peroxiredoxin 5;Pharmaceutical Preparations;pharmacologic;pomalidomide;prevent;Protein Biosynthesis;protein degradation;Protein Synthesis Inhibition;Proteins;Proteolysis;Research;Role;Signal Transduction;Skeletal Muscle;skeletal muscle wasting;Stress;Structural Protein;System;Therapeutic;therapeutic development;therapeutically effective;Transgenic Model;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase;United States National Institutes of Health;Uremia;wasting

PROJECT_TITLE: Protein Nutrition in Experimental Uremia

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]