NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Hematology;Immunization;Orphan Drug;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE  This project will develop and characterize a first-in-class complement inhibitor that holds promise as a much-needed new drug for many complement-mediated hematologic diseases.

PI_NAMEs: LIN, FENG C (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: Affinity;Alpaca;Alternative Complement Pathway;Anemia;Antibodies;Autoimmune hemolytic anemia;B-Lymphocytes;Binding;Biological Assay;Bispecific Antibodies;Blood;Blood Transfusion;Blood Vessels;cell injury;Chimeric Proteins;Classical Complement Pathway;Clinic;Clinical;clinical development;Clinical Trials;Complement;Complement 3;Complement Activation;Complement component C5;Complement Factor D;Complement Inactivators;Complement Membrane Attack Complex;complement system;compstatin;Data;Development;Disease;drug candidate;Drug Kinetics;Enzyme Precursors;Erythrocytes;experience;Explosion;FDA approved;fighting;Future;Hematological Disease;Hemolysis;Human;IgG4;Immunize;improved;In Vitro;in vivo;Infection;Infusion procedures;inhibiting antibody;inhibitor;interest;lead candidate;Lectin;Legal patent;Libraries;Life;Llama;Measures;Mediating;Molecular Biology Techniques;Monoclonal Antibodies;nanobodies;novel;novel therapeutics;paroxysmal nocturnal hemoglobinuria;Pathway interactions;Patients;Peptides;Phage Display;Pharmaceutical Preparations;Phase;Pilot Projects;Pre-Clinical Model;Procedures;Research;screening;success;targeted treatment;technology development;technology platform;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Thrombosis;Time;Treatment Efficacy;Work

PROJECT_TITLE: Development of a first-in-class complement inhibitor for treating complement-mediated hematologic diseases

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-F (M1)]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Diabetes;Genetics;Human Genome;Immunotherapy;Pediatric

ORG_CITY: WORCESTER

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Narrative Type 1 diabetes is an autoimmune disease caused in part by destruction of insulin- producing beta cells in the pancreas by white blood cells called T lymphocytes, which recognize Major Histocompatibility Complex (MHC) molecules presenting beta cells proteins as foreign and attack them as if they were viruses or bacteria infecting the body. Research proposed in this project will determine how MHC polymorphisms influence the susceptibility of succumbing to T1D and how T lymphocytes initiate autoimmune responses. This understanding might lead to better understanding of the autoimmune response in diabetes, and how it could be better diagnosed, controlled, or prevented.

PI_NAMEs: HUSEBY, ERIC S (contact)

PROGRAM_OFFICER_NAME: SPAIN, LISA M

PROJECT_TERMS: Affinity;Alleles;Antibody Therapy;Antigen-Presenting Cells;Antigens;Autoimmune;Autoimmune Diabetes;Autoimmune Diseases;Autoimmune Responses;Autoimmunity;autoreactive T cell;Bacteria;Beta Cell;Biophysics;CASP3 gene;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Compartmentation;Cell Death;Cell Physiology;Clinical;Clone Cells;CRISPR/Cas technology;Cross-Priming;CXCR6 gene;Data;Defect;design;Development;Diabetes Mellitus;Diagnosis;Disabling;Disease;Epitope Mapping;Event;experimental study;G6PC2 gene;Genes;Genetic Models;Genetic Polymorphism;Genetic Predisposition to Disease;genome wide association study;glucose metabolism;Heterozygote;Histocompatibility Antigens Class II;Homeostasis;human disease;Immune mediated destruction;Immune response;Immune Targeting;Immune Tolerance;immunological intervention;imprint;in vivo;Inbred NOD Mice;India;Individual;Inflammatory;insight;Insulin;Insulin-Dependent Diabetes Mellitus;insulitis;islet;Islet Cell;Islets of Langerhans;Leukocytes;Life;Ligands;Location;Lymphocyte;Major Histocompatibility Complex;Mature T-Lymphocyte;Mediating;Methods;MHC Class II Genes;Modeling;mouse model;Mus;novel;Organ;Pancreas;Pathogenesis;Pathogenicity;Pathway interactions;Peptide/MHC Complex;Peripheral;Population;Predisposition;prevent;Process;Property;protective allele;Proteins;Regulatory T-Lymphocyte;Reporter;Research;Residual state;Role;Self Tolerance;Signal Transduction;Single Nucleotide Polymorphism;T cell differentiation;T cell receptor repertoire sequencing;T cell response;T-Cell Activation;T-Cell Development;T-Lymphocyte;Techniques;Testing;Therapeutic;Thymus Gland;Tissues;TNFSF5 gene;transcriptome sequencing;treatment response;Variant;Virus

PROJECT_TITLE: Influence of MHC-II polymorphisms on autoimmune T cell repertoire development and function

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Optical methods are a primary technique for the study of cellular physiology. This research concerns the development of new optical probes that will enable photocontrol of membrane excitability in vitro and in vivo. Since almost all cell signaling is bidirectional or symbiotic, these new methods will revolutionize our ability to control function and therefore uncover many fresh details of cell physiology.

PI_NAMEs: ELLIS-DAVIES, GRAHAM  (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TITLE: Light-driven control of neurons in vitro and in vivo


ADMINISTERING_IC: CA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Hematology;Lymphatic Research;Lymphoma;Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative: Chronic Lymphocytic Leukemia (CLL), which remains incurable despite recent advances in targeted therapeutics, relies on metabolic alterations to meet the immense energetic demands of sustained growth and persist in diverse environments including the blood, spleen, lymph nodes and bone marrow. Sphingolipids, particularly ceramides, hold great therapeutic potential as they can regulate many cellular pathways that impinge on metabolic systems and the delivery of these bioactive molecules has been shown to induce cell death in both in vitro and in vivo models of CLL. The F99 phase of this proposal will establish the mechanism by which exogenous ceramide induced ganglioside accumulation leads to mitochondrial dysfunction and cell death in CLL, while the K00 phase will leverage CRISPR screening and advanced in vivo mitochondrial characterization to better understand the role of sphingolipids and their therapeutic potential in mitochondrial transfer and glioma stem cell support of glioblastoma.

PI_NAMEs: VASS, LUKE REMINGTON (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Accounting;adult leukemia;Agammaglobulinaemia tyrosine kinase;Apoptotic;Area;Astrocytes;Automobile Driving;B-Cell Antigen Receptor;Binding;Binding Proteins;Bioenergetics;Biological Assay;Biology;Blood;Bone Marrow;cancer cell;Cancer Research Project;Cell Death;Cell Death Induction;Cell Line;Cells;Cellular Metabolic Process;Ceramides;Cessation of life;Chronic Lymphocytic Leukemia;chronic lymphocytic leukemia cell;Collaborations;CRISPR screen;Defect;defined contribution;Diagnostic;Disease;Electron Microscopy;Electron Transport Complex III;Energy Metabolism;Environment;Gangliosides;Genetic Transcription;Glioblastoma;Glioma;Glucosylceramides;Glycolysis;Glycosphingolipids;Goals;Growth;Impairment;In Vitro;in vivo;in vivo Model;insight;Knowledge;Label;Learning Skill;leukemia;Link;lipid metabolism;Lipids;lymph nodes;LYN gene;Malignant Neoplasms;Mediating;Metabolic;Metabolism;metabolomics;Mitochondria;mitochondrial dysfunction;Modeling;Monitor;mutant;nanoliposome;novel;novel therapeutic intervention;novel therapeutics;Organoids;Oxidative Phosphorylation;Pathway interactions;Patients;Phase;Phosphorylation;Phosphorylation Site;Phosphotransferases;Play;Positron-Emission Tomography;Post-Translational Protein Processing;Postdoctoral Fellow;pre-doctoral;Proliferating;Proteins;Proteomics;Receptor Signaling;Refractory;Relapse;Research;Research Project Grants;Resistance;response;restoration;Role;Sampling;Shunt Device;Sialic Acids;Signal Pathway;Signal Transduction;Small Interfering RNA;Source;Sphingolipids;Spleen;Stat3 protein;stem cells;Stimulus;Supporting Cell;System;targeted treatment;Therapeutic;therapeutic target;Time;Training;Translating;Up-Regulation

PROJECT_TITLE: Ceramide and Cell Metabolism: Defining the Role of Sphingolipids in Modulating Mitochondrial Bioenergetics of Chronic Lymphocytic Leukemia

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RTRB-U (M1)]


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: ANN ARBOR

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative Advanced melanoma is the most serious type of skin cancer with poor prognosis. Here, we propose to investigate multivalent small circular RNA vaccines that generate potent and long-lasting immune responses for melanoma combination immunotherapy. The results from this project are anticipated to define the design guidelines of these novel vaccines and ultimately improve the clinical practice and outcomes of current melanoma treatments.

PI_NAMEs: WANG, XIANG-YANG SHAWN;ZHU, GUIZHI  (contact)

PROGRAM_OFFICER_NAME: CHRISTEN, JAYNE

PROJECT_TERMS: adaptive immune response;Address;Adjuvant;Antigen Presentation;Antigen-Presenting Cells;Antigens;ART protein;Biodistribution;Biological Availability;cancer immunotherapy;CD8-Positive T-Lymphocytes;circular RNA;Clinical;clinical practice;Cold Chains;Combination immunotherapy;Complex;Consumption;design;DNA;Dose;Double-Stranded RNA;Elements;Engineering;Evaluation;Genetic Transcription;Genomics;Goals;Guidelines;HLA Antigens;Human;humanized mouse;Immune;immune activation;immune checkpoint;immune checkpoint blockade;Immune response;Immunity;immunogenic;Immunologic Memory;Immunologic Sensitization;Immunologic Stimulation;immunoregulation;Immunosuppression;Immunotherapy;improved;In Vitro;Inflammation;Innate Immune Response;innovation;Internal Ribosome Entry Site;Lead;Life;lipid nanoparticle;lymph nodes;Malignant Neoplasms;manufacture;MEL Gene;Melanoma;Melanoma patient;Melanoma Tumor;Melanoma Vaccine;Messenger RNA;Modification;Molecular;Mus;nanocarrier;nanoparticle;Natural Immunity;neoantigens;neoplasm immunotherapy;novel;novel vaccines;Nucleosides;Nucleotides;old mice;Oligonucleotides;Outcome;Patients;Pattern recognition receptor;Peptides;pre-clinical;Process;Production;Prognosis;protein kinase R;Proteolytic Processing;RNA;RNA vaccine;Role;Safety;Scheme;Skin Cancer;Structure;T cell response;T cell therapy;T memory cell;T-Lymphocyte;Testing;thermostability;Time;Toxicology;Transgenic Organisms;Translating;Translations;Transportation;Treatment Efficacy;Treatment-related toxicity;tumor;Tumor Antigens;Tumor Immunity;tumor-immune system interactions;Tumor-infiltrating immune cells;uptake;Vaccines;vaccinology;Viral Vector;Virulent;Xenograft procedure;young adult

PROJECT_TITLE: Multivalent Small Circular mRNA Vaccines for Melanoma Combination Immunotherapy

STUDY_SECTION: TIO

STUDY_SECTION_NAME: Translational Immuno-oncology Study Section[TIO]


ADMINISTERING_IC: OD

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Bioengineering;Data Science;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: CHAPEL HILL

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Narrative: Linking differences in our genes to the molecular and physiological mechanisms underlying disease remains a major challenge. Here we use data from the Common Fund Data Ecosystem (CFDE) along with two advanced data science technologies, knowledge graphs and visible neural network, to develop a new method for revealing the molecular pathway of genetically complex disorders. We will initially develop this tool for data related to Type 2 Diabetes, but have the ultimate goal of extending this approach to other genetic studies.

PI_NAMEs: CHUNG, CHENG-HAN  (contact)

PROGRAM_OFFICER_NAME: PAPANICOLAOU, GEORGE

PROJECT_TERMS: Adopted;Affect;Architecture;base;biobank;Biological;Biological Assay;Biological Models;Biological Process;Black Box;Clinic;Code;cohort;Collection;Complex;Complex Genetic Trait;Computational Biology;Data;data ecosystem;data integration;Data Reporting;data resource;Data Science;Data Scientist;Data Set;Data Sources;data tools;Disease;disease phenotype;diverse data;Ecosystem;experience;Funding;Gene Combinations;Gene Expression Regulation;gene function;Genes;Genetic;Genetic Diseases;genetic predictors;Genetic Risk;Genetic study;genetic variant;genome wide association study;genome-wide;Genotype;Goals;Health;improved;insight;interest;Intervention;Knowledge;knowledge graph;knowledge integration;large datasets;Link;Logic;Machine Learning;machine learning model;metabolomics;Methods;Modeling;Molecular;molecular phenotype;Nature;Network-based;neural network;neural network architecture;Neural Network Simulation;Neurons;Non-Insulin-Dependent Diabetes Mellitus;Ontology;Other Genetics;Pathway interactions;Pattern;Pharmaceutical Preparations;Phenotype;phenotypic data;Physiological;Polygenic Traits;Population Genetics;Process;programs;Publishing;Research Personnel;Resources;response;Risk;risk prediction;Source;Statistical Study;success;supervised learning;Technology;tool;Training;trait;Trans-Omics for Precision Medicine;Translating;Translations;Variant;Veterans;whole genome;Work

PROJECT_TITLE: GeneSight: Advancing Insights into Complex Genetic Traits through CFDE-Enhanced Knowledge Graphs

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IVBH-A (50)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Cancer;Genetics;Infectious Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: WISTAR INSTITUTE

ORG_STATE: PA

PHR: EBV infection usually has a benign outcome, yet nearly 144,000 people annually die of untreatable malignancies caused by latent EBV infection of lymphoid or epithelial cells. EBV protein expression is the oncogenic driver and progressive force in B cell lymphomas. This current proposal will reveal new epigenetic and metabolic vulnerabilities that can be leveraged to treat EBV+ B malignancies specifically.

PI_NAMEs: TEMPERA, ITALO  (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: 3-Dimensional;Adopted;Affect;Anabolism;Architecture;B Cell Proliferation;B-Cell Lymphomas;B-Lymphocytes;Benign;Binding;cancer cell;Cell Compartmentation;Cell Nucleus;Cells;Cessation of life;Chromatin;Chromatin Loop;Chromatin Structure;clinically relevant;Complex;Coupled;Couples;cytotoxicity;Data;Enzymes;Epigenetic Process;epigenome;Episome;Epithelial Cells;Epstein-Barr Virus Infections;Epstein-Barr Virus latency;Epstein-Barr Virus-Related Malignant Neoplasm;Funding;Gene Expression;Gene Expression Regulation;gene repression;Genes;Genetic Transcription;Genome;Goals;Hematologic Neoplasms;Heterochromatin;histone modification;Histones;Human Herpesvirus 4;in vivo;infected B cell;inhibitor;inhibitor therapy;insight;latent gene expression;Latent virus infection phase;Link;LMP1;Lymphoid Cell;macroH2A histone;Malignant Neoplasms;Mediating;Metabolic;Metabolism;Nuclear;NuRD complex;Oncogenic;Outcome;Pathway interactions;Persons;Physiological;Play;Poly(ADP-ribose) Polymerase Inhibitor;prevent;Process;programs;promoter;protein expression;Proteomics;recruit;Regulation;Reporting;Role;Signal Transduction;Structure;Testing;Therapeutic;three dimensional structure;Translating;Treatment Effectiveness;Tumor Burden;Variant;Viral;Viral Genes;Viral Genome;Viral Proteins;virology;Virus Activation;Virus Latency;Work

PROJECT_TITLE: Regulation of Viral Chromatin Architecture During EBV Latency

STUDY_SECTION: MCV

STUDY_SECTION_NAME: Molecular and Cellular Biology of Virus Infection Study Section[MCV]


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF OPTOMETRY/OPHT TECH

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Brain Disorders;Eye Disease and Disorders of Vision;Neurosciences;Pediatric

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Ocular misalignment (strabismus) and compromised visual acuity (amblyopia) are visual developmental disorders that affect a vast number of children born every year in the United States and around the world. Prior to application of treatment in humans, a better understanding of neural mechanisms and pre-clinical testing in non-human primate models are needed to help develop and refine rationally based therapy. This project will a) combine various physiological methods and behavior investigation in an animal model for strabismus to investigate how gaze is re-oriented to visual stimuli and b) develop and test in the non-human primate, a novel treatment strategy for amblyopia that has shown promise in cat and mouse models.

PI_NAMEs: DAS, VALLABH E (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Adult;Affect;Age;Amblyopia;Animal Model;animal old age;Animals;Area;Autopsy;Behavior;Behavioral;Biometry;Brain;Characteristics;Child;cohort;congenital cataract;Contrast Sensitivity;Control Groups;conventional therapy;Coupled;critical period;Curiosities;Data Analyses;deprivation;Development;developmental disease;Disabling;Disease;dosage;Dose;Environment;Evaluation;experimental study;extrastriate visual cortex;Eye;Eye Movements;Felis catus;Fostering;Frequencies;frontal eye fields;gaze;Histologic;Human;Image;Infant;Injections;innovation;intravitreal injection;Investigation;juvenile animal;Life;Location;Maps;Methods;Microinjections;Modeling;Monkeys;monocular;monocular deprivation;Motor;mouse model;Movement;Mus;neural;neural circuit;neuromechanism;Neurons;nonhuman primate;novel;novel therapeutic intervention;oculomotor;Optic Nerve;Pattern;Physiological;Preclinical Testing;Predisposition;preference;Probability;Process;Public Health;Pupil;Race;Recovery;Resistance;response;Retina;retinal nerve fiber layer;Role;Saccades;Safety;salt balance;sample fixation;Seminal;Sensory;Severities;sight restoration;Stimulus;Strabismus;Structure;superior colliculus Corpora quadrigemina;sustained recovery;Tail;Testing;Tetrodotoxin;treatment comparison;Treatment Efficacy;treatment strategy;United States;vector;Vision;vision development;Vision Tests;Visual;Visual Acuity;Visual evoked cortical potential;Visual Fields;Visual impairment;visual stimulus;Work

PROJECT_TITLE: Binocular Coordination of Eye Movements

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


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

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: NARRATIVE Cellular plasticity drives tumor heterogeneity and drug resistance; however, we lack an understanding of its underlying molecular mechanisms. In our preliminary work, we identified a mode of non-genetic adaptation in response to therapeutic intervention in clinical and pre-clinical models. In this proposal, we present an approach to dissect the cellular plasticity programs in non-small cell lung cancer (NSCLC) for disrupting and predicting the chromatin landscape that underpins cancer cell state transitions involved in drug resistance.

PI_NAMEs: PATEL, AYUSHI  (contact)

PROJECT_TERMS: Cancer Biology;cancer cell;Cancer Etiology;cancer type;Cell Physiology;Cells;Chromatin;chromatin remodeling;Chromatin Remodeling Factor;Clinical;clinically relevant;clinically significant;Combined Modality Therapy;Coupled;CRISPR screen;Data;Data Set;Development;Diagnosis;differential expression;Drug resistance;Epigenetic Process;epigenomics;Epithelium;Evolution;Genes;Genetic;Genetic Transcription;Goals;Heterogeneity;Histologic;improved;inhibitor;insight;Joints;Literature;Lung Adenocarcinoma;lung cancer cell;Malignant neoplasm of lung;Malignant Neoplasms;Maps;Mediating;Mesenchymal;Modeling;Molecular;mortality;mouse model;multiple omics;Mus;Mutation;Neoplasm Metastasis;neoplastic cell;neural network;non-genetic;Non-Small-Cell Lung Carcinoma;novel;novel strategies;Oncogenes;Organoids;Outcome;Patients;permissiveness;Pharmaceutical Preparations;Phenotype;Population;Postdoctoral Fellow;potency testing;Pre-Clinical Model;predictive modeling;Prevalence;prevent;Primary Neoplasm;Process;Prognosis;programs;Recording of previous events;Research;Research Project Grants;response;Role;Route;Sampling;single cell ATAC-seq;single-cell RNA sequencing;small molecule inhibitor;Squamous Cell Lung Carcinoma;targeted treatment;Technology;Testing;Therapeutic;Therapeutic Intervention;therapy resistant;transcriptome;tumor;Tumor Biology;tumor heterogeneity;Tumor Suppressor Proteins;tumorigenesis;Validation;Work

PROJECT_TITLE: Resolving epigenetic determinants of cellular plasticity programs in non-small cell lung cancer


NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Cardiovascular;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Physical Activity;Precision Medicine;Prevention

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative Cardiorespiratory fitness (CRF) is an integrative measure of cardiopulmonary and metabolic health and independent predictor of long-term survival that can be improved with exercise training. Despite this, limited knowledge exists regarding the biochemical pathways that underlie CRF. Our goal is to combine novel blood protein profiling technology with genetics and gene expression databases from Common Fund resources to identify promising candidate protein determinants of CRF – findings that set the stage for further mechanistic studies.

PI_NAMEs: ROBBINS, JEREMY  (contact)

PROJECT_TERMS: Adult;Amides;arm;biobank;Biochemical;Biochemical Pathway;Biogenesis;Biological Assay;Biology;Blood Proteins;Body System;Body Weight;candidate identification;Cardiac Myocytes;Cardiopulmonary;cardiorespiratory fitness;Cardiovascular system;Cell model;Ceramides;Circulation;CISH gene;Clinical;Complex;Data;Data Set;Disease;EFRAC;Enzymes;Exercise;exercise training;experimental study;Family;fitness;functional gain;functional genomics;Funding;Future;G-Protein-Coupled Receptors;Gene Expression;gene expression database;Generations;Genetic;genetic association;Genetic Transcription;genome sequencing;Genomics;Genotype;Genotype-Tissue Expression Project;Glutamine;Goals;Health;Health Benefit;Heart;Heart failure;Human;Impairment;improved;In Vitro;insight;instrument;inter-individual variation;interest;Investigation;Knock-out;Knowledge;Laboratories;Ligands;Lipids;Lung;Measures;Mediating;Mediator;member;Metabolic;Metabolism;metabolomics;Mitochondria;Modeling;Molecular;Molecular Profiling;mortality;mortality risk;Multiomic Data;Myocardium;novel;Outcome;Participant;Pathway interactions;Peptides;Pharmacotherapy;Phenotype;Physical activity;Physiological;Plasma;Plasma Proteins;preservation;protein profiling;Proteins;Proteomics;Quantitative Trait Loci;Randomized, Controlled Trials;Regulation;Research Design;Resources;response;Role;sedentary;Signal Transduction;Signaling Molecule;skeletal;Skeletal Muscle;small molecule;Source;standard measure;Syndrome;targeted treatment;Technology;Tissues;Training;trait;Trans-Omics for Precision Medicine;Transducers;Triage;trial design;TRP channel;United States National Institutes of Health;Variant;VO2max;whole genome;Work

PROJECT_TITLE: Integrative analysis of genomics and proteomics to identify candidate molecular transducers of cardiorespiratory fitness


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Psychosis;Rehabilitation;Schizophrenia;Serious Mental Illness

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Public Health Relevance Statement (Narrative) (from Parent Award) Schizophrenia is the 5th leading cause of disability in the world, affecting 51 million people in which patients suffer from cardinal deficits in self-agency (i.e., the fundamental experience of being the agent of one's own thoughts and actions). These deficits directly contribute to debilitating psychotic symptoms, and show limited response to pharmacological treatments with up to 40% of patients with schizophrenia (SZ) remaining symptomatic, thus compelling the need to identify the neurophysiology underlying self-agency deficits to guide new treatment development. Findings from this proof-of-concept study will delineate: (i) the underlying cognitive and neural cause of self-agency deficits in schizophrenia, (ii) responsiveness to new neurostimulation interventions targeting a novel neural target in the medial prefrontal cortex, and (iii) mechanisms of durability and generalizability, revealing how improvements in critical self-agency abilities can generalize to improvements in general cognition, symptoms and life quality in schizophrenia for future TMS treatment development.

PI_NAMEs: SUBRAMANIAM, KARUNA  (contact)

PROGRAM_OFFICER_NAME: ANKUDOWICH, ELIZABETH

PROJECT_TERMS: Affect;auditory feedback;Behavior Therapy;Behavioral;Biological;Biological Assay;Cognition;Cognitive;cognitive training;Data;Development;disability;Disease;Distal;effective therapy;experience;Frequencies;Future;Goals;Hearing;improved;Intervention;Judgment;Magnetoencephalography;Measures;Medial;Mediating;memory retrieval;Modeling;Monitor;neural;neural correlate;neural network;Neurobiology;neuromechanism;neurophysiology;novel;Outcome;Output;parent project;Patients;Persons;Pharmaceutical Preparations;Pharmacological Treatment;Prefrontal Cortex;Psychoses;psychotic;psychotic symptoms;public health relevance;Quality of life;Randomized, Controlled Trials;Regimen;repetitive transcranial magnetic stimulation;Research;response;Retrieval;Role;Schizophrenia;Site;Speech;Symptoms;Testing;therapeutic target;therapy development;Thinking;Time;Transcranial magnetic stimulation

PROJECT_TITLE: Causal Role of Medial Prefrontal Neural Activity in Self-Agency in Schizophrenia  (Admin Suppl)

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Cancer-cachexia is a wasting syndrome that occurs in up to 80% of cancer patients and is the primary cause of death for 20-40% of cancer patients. While obesity has been suggested to protect against the severity of cachexia due to having ‘more to spare’, published work from my F31 demonstrates that obesity is not protective against cachexia and suggests exacerbated impairments to mitochondrial function and quality control with a particular disruption in the removal of damaged mitochondria. The goal of my F99/K00 is to 1) understand the microbial and metabolic perturbations with cancer cachexia in the obese state (F99), and 2) establish microbiome-mitochondrial interactions in obesity associated cancer cachexia and identify strategies for intervention (K00).

PI_NAMEs: CARDACI, THOMAS  (contact)

PROGRAM_OFFICER_NAME: ELJANNE, MARIAM

PROJECT_TERMS: Activities of Daily Living;Automobile Driving;Award;Behavior;Biogenesis;Biological Assay;Cachexia;Calcium;Cancer Cachexia;cancer diagnosis;Cancer Model;Cancer Patient;cancer therapy;carcinogenesis;career;career development;Cause of Death;Data;design;Development;Development Plans;Disease;dysbiosis;Enzymes;Epidemiology;Excision;experience;Fellowship;Functional dependence;Functional disorder;Goals;gut dysbiosis;gut microbes;gut microbiome;gut microbiota;Homeostasis;Impairment;improved;Institution;Intervention;Knowledge;Lewis Lung Carcinoma;Link;Literature;Maintenance;Malignant Neoplasms;Measures;Metabolic;Metabolic Pathway;Metabolism;Microbe;microbial;microbiome;microbiota;Mitochondria;mitochondrial dysfunction;Modeling;Morbidity - disease rate;Morphology;multiple omics;Mus;Muscle Fibers;muscle form;Muscle function;Muscle Mitochondria;novel;Obese Mice;Obesity;Obesity associated cancer;Overweight;Oxidation-Reduction;Pathogenesis;Pathology;Patients;Phase;Phenotype;Population;Prevention;protein degradation;Publishing;Quality Control;Quality of life;Reporting;Research;Research Personnel;Research Project Summaries;Role;Severities;Skeletal Muscle;skills;Technical Expertise;Testing;Thinness;Time;Training;transcription factor;Treatment outcome;Treatment-Related Cancer;tumor;Wasting Syndrome;Weight;Work

PROJECT_TITLE: Microbiome-Mitochondrial Interactions Driving Cancer-Induced Cachexia in the Obese State


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences

ORG_DEPT: PSYCHOLOGY

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: PROJECT NARRATIVE This project will use behavioral and functional neuroimaging techniques to investigate how arousal states alter vision-related neural responses. Results will inform and provide critical constraints to models of the human visual system, which provide a necessary framework for the development of diagnostic tools and treatments for clinical disorders that involve deficits of central visual processing. Moreover, the studies could yield generalizable insights about how arousal modulates neural processing across brain systems, thereby informing the development of diagnostic tests and interventions for conditions that involve atypical arousal levels.

PI_NAMEs: JEHEE, JANNEKE ;LING, SAM  (contact)

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TERMS: adjudication;Affect;analytical tool;Arousal;auditory stimulus;Automobile Driving;Beds;Behavior;Behavioral;Brain;Clinical Treatment;Cognition;Computer Models;diagnostic development;Diagnostic tests;diagnostic tool;Disease;Emotional;Environment;Exposure to;Frequencies;Functional Magnetic Resonance Imaging;generative models;Goals;Heterogeneity;Human;insight;Intervention;Knowledge;locus ceruleus structure;Measurement;Measures;Methods;Modeling;Moods;neglect;neural;neural information processing;neuroimaging;non-invasive system;norepinephrine system;novel;Output;Participant;Perception;Performance;Play;Population;Probability;Process;Property;Psychophysics;Research;response;Role;sensory system;Shapes;Startle Reaction;Stimulus;System;Techniques;Testing;theories;Time;Uncertainty;Vision;vision science;Visual;Visual Cortex;visual information;visual processing;Visual System;Waxes;Work

PROJECT_TITLE: Investigating the Effect of Arousal on Visual Processing

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Data Science;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Lung;Lung Cancer;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: OMAHA

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative In this project, we propose to develop an accurate and cost-effective machine learning framework for lung cancer subtype identification by integrating multi-modal genomics data within and beyond the Common Fund data sets. If successful, our study will directly improve downstream lung cancer diagnosis, prognosis, and treatment. Our proposed framework in this study can also be extensible to identifying subtypes of other cancers.

PI_NAMEs: WAN, SHIBIAO  (contact);WANG, JIEQIONG

PROJECT_TERMS: Accounting;Address;alcohol use disorder;anti-cancer research;Bioinformatics;biomarker discovery;Biometry;cancer biomarkers;cancer classification;cancer diagnosis;Cancer Etiology;cancer subtypes;cancer type;cell type;Cells;Cessation of life;Collaborations;Computational Biology;Consumption;cost;cost effective;Cytogenetic Analysis;Data;Data Set;deep learning;Detection;Diagnosis;diverse data;Epigenetic Process;epigenomics;experience;explainable machine learning;flexibility;Foundations;Funding;Gene Transfer;Genes;genetic signature;genomic data;Genomics;Genotype-Tissue Expression Project;Goals;Human BioMolecular Atlas Program;image processing;Imaging Techniques;Immunophenotyping;improved;individualized medicine;kernel methods;Knowledge;Machine Learning;machine learning framework;machine learning method;machine learning model;Malignant neoplasm of lung;Malignant Neoplasms;Medical Imaging;Methods;Modeling;Molecular;Molecular Profiling;Morphology;multidisciplinary;multimodality;Multiomic Data;multiple omics;Mutation;Nervous System Disorder;Neurosciences;next generation sequencing;Non-Small-Cell Lung Carcinoma;novel;Outcome;Patients;Performance;Positioning Attribute;Process;Prognosis;Research;risk stratification;Running;Sampling;Selection for Treatments;single-cell RNA sequencing;small cell lung carcinoma;specific biomarkers;synergism;therapy design;Time;transcriptome sequencing;transcriptomics;treatment optimization;United States;X-Ray Computed Tomography

PROJECT_TITLE: Leveraging Heterogenous Common Fund Data Sets and Beyond for Identifying Lung Cancer Subtypes


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Genetics;Hematology;Human Genome;Infectious Diseases;Pediatric;Pediatric Cancer;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE Understanding predisposition to hematological diseases, such as pediatric Acute Myeloid Leukemia (pAML) is crucial for deciphering disease pathogenesis, finding treatment targets, and selecting appropriate donors for bone marrow transplant. Here, I propose to study deleterious germline variants in cohorts of pAML from the TARGET and Kids First! Consortiums, and to develop the necessary techniques to model the effects of variants in vivo. I will build on the training and knowledge in the next phase of my career, in which I will study the structural, splicing, and synonymous germline genetic variation and viral infections in the etiology of pediatric and early- onset AML.

PI_NAMEs: HARMON, LAUREN MARIE (contact)

PROJECT_TERMS: Acceleration;Acute Myelocytic Leukemia;Address;Adult;Affect;American;Attention;Autoimmune Diseases;Award;Binding;Binding Sites;Biological;Biological Assay;Blood;Bone Marrow Transplantation;career;catalyst;CBFA2T1 gene;CEBPA gene;Child;Childhood;Childhood Acute Myeloid Leukemia;Childhood Leukemia;chimeric gene;Classification;cohort;computer infrastructure;Congenital Abnormality;contig;CREBBP gene;CRISPR/Cas technology;Cytomegalovirus;Data;Defect;Derivative Chromosome;Development;Disease;Disease remission;Disease susceptibility;disease-causing mutation;disorder risk;DNA Double Strand Break;Donor person;dosage;Double Strand Break Repair;early onset;effective therapy;Enhancers;EP300 gene;Etiology;Fellowship;Foundations;Frequencies;gel electrophoresis;Gene Expression;Gene Fusion;gene therapy clinical trial;Genes;Genetic;Genetic Counseling;genetic element;Genetic Predisposition to Disease;genetic variant;Genetic Variation;Genomics;Germ Lines;Germ-Line Mutation;Goals;Guidelines;Hematological Disease;Hematopoietic stem cells;Herpesviridae;high risk;Human;Human Genome;Immune response;improved;in vivo;Incidence;Individual;Inflammation;inhibitor;insight;Knowledge;leukemia;leukemogenesis;Liquid substance;Live Birth;Malignant Childhood Neoplasm;Medical Genetics;medical schools;Modeling;mutant;Mutation;new therapeutic target;novel;NUP98 gene;Oncogene Activation;Oncogenes;Oncogenic;Participant;Pathogenesis;pathogenic virus;Pathogenicity;Pathway interactions;Patients;Pediatric cohort;Phase;Pilot Projects;Population;Postdoctoral Fellow;Predisposition;prenatal;Prevalence;Prognosis;Prophylactic treatment;protein protein interaction;Proteins;Ramp;Research;Research Personnel;Research Project Grants;Risk;Risk Factors;risk stratification;RNA Splicing;Role;RUNX1 gene;Sample Size;Sampling Biases;Scanning;screening;Short Tandem Repeat;skills;Solid;Somatic Mutation;Spottings;stem cells;Susceptibility Gene;t(8;21) acute myeloid leukemia;Techniques;Therapeutic;Tissues;Training;Transcript;Transcription Coactivator;transcription factor;transcriptome;transcriptomics;treatment planning;treatment strategy;tumor;Untranslated RNA;Validation;Variant;Viral;Viral Genome;viral genomics;Viral Vector;Virus Diseases;virus genetics;Virus Integration;whole genome;Work;Zebrafish

PROJECT_TITLE: Determinants of susceptibility to pediatric acute myeloid leukemia


ORG_NAME: NATIONAL DISEASE RESEARCH INTERCHANGE

PHR: Project Narrative The importance of human biospecimens in research continues to grow, and the Human Tissue and Organs for Research Resource (HTORR) program provides innovative services to support investigators that require human tissues and organs for their research. Over the past 4 years, over 500 scientific papers were published by investigators that received biospecimens from HTORR, demonstrating HTORR's indispensable contribution to the research community and the impact of these services on the search for new treatments and cures for common and rare diseases. Importantly, as new tools and technologies are developed, the resources supporting this work also need to evolve and modernize to be able to continue providing the best quality resources to facilitate rigor and reproducibility throughout the research communities that we serve.

PI_NAMEs: BELL, THOMAS J (contact)

PROGRAM_OFFICER_NAME: LI, XIANG-NING

PROJECT_TERMS: 15 year old;Accreditation;Address;American;authority;biobank;Biomedical Research;cold temperature;Collection;college;commune;Communication;Communities;Competence;Computer software;cost;Cryopreservation;Data Reporting;Data Storage and Retrieval;Disease;Documentation;Elements;Ensure;Equipment;equipment acquisition;Event;Exercise;Freezing;Frequencies;Funding;Funding Opportunities;Future;Grant;Guidelines;Hot Spot;Hour;Human;human tissue;Humidity;improved;Informatics;Information Systems;Infrastructure;innovation;Logistics;Maintenance;Manuals;Maps;Measurement;meetings;Methods;Mission;Modernization;Monitor;Operating System;operation;Organ;Paper;Pathologist;Periodicals;Principal Investigator;Process;process improvement;programs;Publishing;R24;Rare Diseases;Records;Reporting;Reproducibility;Research;research facility;Research Personnel;Research Support;Resources;Sampling;sensor;Services;System;Technology;Temperature;Time;tool;United States National Institutes of Health;Update;Vendor;wireless;Work

PROJECT_TITLE: HTORR Cold Storage Temperature Monitoring Modernization

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 DCAI-U (91)]


NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Lung;Organ Transplantation;Transplantation

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Long-term patient outcomes following lung transplantation are poor, in part because it is challenging to diagnose respiratory infections and to distinguish infection from rejection. We have developed innovative approaches that use bacteriophages in peripheral blood to diagnose respiratory infections. These studies may lead to revolutionary, non-invasive diagnostic approaches to monitor patient health following lung transplantation.

PI_NAMEs: BOLLYKY, PAUL L (contact)

PROGRAM_OFFICER_NAME: KEHN, PATRICIA J

PROJECT_TERMS: allograft rejection;Allografting;Antimicrobial Resistance;antimicrobial resistant pathogen;Area;Bacteria;Bacteriophages;Bar Codes;Biological Markers;Blood specimen;Bronchoalveolar Lavage Fluid;Caring;cell free DNA;Cells;Characteristics;Chronic;Cohort Studies;Communicable Diseases;Data;Diagnosis;Diagnostic;diagnostic strategy;Dictionary;DNA;DNA Viruses;Explosion;fungus;Genus Mycobacterium;Graft Rejection;Health;High-Throughput Nucleotide Sequencing;Human;Immunocompromised Host;Infection;innovation;insight;interest;Life;Longitudinal cohort;Longitudinal cohort study;Lung;lung colonization;Lung infections;Lung Transplantation;Medicine;microbial;Monitor;mycobacterial;next generation sequencing;non-invasive monitor;noninvasive diagnosis;novel;novel strategies;Organism;Parasites;pathogen;pathogenic microbe;Patient Monitoring;Patient-Focused Outcomes;Patients;peripheral blood;Phenotype;Plasma;Pneumonia;Population Dynamics;Procedures;prospective;Protocols documentation;resistant strain;respiratory;respiratory allograft;respiratory pathogen;Respiratory Tract Infections;Sampling;Specificity;stool sample;Symptoms;Technology;Testing;Time;Tissues;Transplant Recipients;Variant;Viral;Virus;Work

PROJECT_TITLE: Non-invasive Monitoring for Infections and Rejection after Lung Transplantation

STUDY_SECTION: LCMI

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


ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative Obesity increases the risk of colorectal cancer (CRC) development in both men and women by changing the tumor micronevironment. This proposal will identify signaling molecules that are responsible for promoting tumor development during obesity and determine potential targets for cancer therapy for CRC patients with an obese body mass index.

PI_NAMEs: HAQUE, PARSA  (contact)

PROJECT_TERMS: 3-Dimensional;Abdomen;Adipocytes;Adipose tissue;Anti-Inflammatory Agents;ApcMin/+ mice;Binding;Biological Assay;Biology;Body mass index;cancer cell;Cancer Patient;Cancer Prognosis;Cell Communication;Cells;Chemicals;chemotherapy;colon cancer cell line;colon cancer patients;Colorectal Cancer;colorectal cancer risk;colorectal cancer treatment;Communication;Cytoplasm;Data;Deposition;design;Development;diet-induced obesity;Disease-Free Survival;Distant;Environment;Enzymes;experience;extracellular vesicles;Genes;Glycolysis;Glycolysis Induction;Glycolysis Inhibition;Goals;Grant;Growth;HCT116 Cells;Human;Immune;Immune signaling;Immunological Models;In Vitro;in vivo;indexing;Individual;Infiltration;Inflammatory;inorganic phosphate;intestinal tumorigenesis;Isomerase;Isotope Labeling;knock-down;Knowledge;Laboratories;Lactic acid;Lead;Macrophage;Malignant Neoplasms;Measures;Mediating;Membrane Lipids;men;Mentors;Messenger RNA;Metabolic;Metabolism;Molecular;Molecular Target;mortality;mouse model;Mus;neoplastic cell;new therapeutic target;Non obese;novel;novel therapeutic intervention;Obese Mice;obese patients;Obesity;Oncogenic;Organ;Organoids;Parents;Pathway interactions;Phase;Phenotype;Physiology;Population;programs;Proteins;Proteomics;Regulation;Research;Research Proposals;Risk;Role;Signal Pathway;Signal Transduction;Signaling Molecule;spheroids;targeted cancer therapy;targeted treatment;Technical Expertise;Testing;Therapeutic;Tissues;Training;transcriptome sequencing;tumor;Tumor Burden;tumor growth;tumor immunology;tumor initiation;tumor microenvironment;tumor progression;Tumor Promotion;Tumor-Derived;tumorigenesis;tumorigenic;Vesicle;vesicular release;Visceral;Woman

PROJECT_TITLE: The alterations caused by obese extracellular vesicles on colorectal cancer tumor microenvironment


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Contraception/Reproduction;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Microbiome;Nutrition;Obesity;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Women's Health Research

ORG_CITY: FORT COLLINS

ORG_DEPT: OTHER CLINICAL SCIENCES

ORG_NAME: COLORADO STATE UNIVERSITY

PHR: Project Narrative Maternal obesity with hyperphagia is a risk factor for preeclampsia, pregnancy hypertension, and offspring cardiometabolic disease. In utero programming of female offspring during preeclampsia contributes to the lifecycle of disease in women as a sex and gender. Investigating the maternal obesogenic environment is warranted to halt the transgenerational programming of cardiometabolic disease risk.

PI_NAMEs: SONES, JENNIFER LIFORD (contact)

PROGRAM_OFFICER_NAME: VARAGIC, JASMINA

PROJECT_TERMS: Acetates;Acetic Acids;Adult;Adult Children;adverse pregnancy outcome;angiogenesis;Angiogenesis Inhibitors;Anti-Hypertensive Agents;Anti-Inflammatory Agents;Attenuated;attenuation;Bacteria;Binding;Blood Pressure;Body Weight decreased;cardiac angiogenesis;Cardiometabolic Disease;cardiometabolic risk;cardiometabolism;Clinical;Colon;comorbidity;comparison control;Data;Development;Disease;disorder risk;Eating;Embryo;Embryo Transfer;Energy Metabolism;Environment;Etiology;experimental study;feeding;Female;Fenbendazole;fetal;Fetal Growth Retardation;fetal programming;Fetus;FFAR2 gene;FFAR3 gene;fitness;Functional disorder;Gender;gender behavior;glucagon-like peptide 1;Goals;gut dysbiosis;gut microbiome;Health;heart function;Hyperphagia;Hypertension;hypertensive;improved;in utero;in vivo;Inflammation;Inflammatory;inflammatory marker;innovation;Intervention;Lactobacillus;Life;Life Cycle Stages;Ligands;Link;male;maternal hypertension;maternal obesity;maternal weight;Maternal-Fetal Exchange;Measures;Metabolic;Metabolism;microbial;microbiome;Modeling;mortality;mouse model;Multiple Organ Failure;Mus;Nonesterified Fatty Acids;novel;Obesity;obesogenic;offspring;oral supplementation;Outcome;Placenta;Play;Pre-Eclampsia;Pregnancy;pregnancy hypertension;pregnant;Pregnant Women;prenatal;prepregnancy;prevent;programs;Proteinuria;receptor;Resolution;Risk;Risk Factors;Role;Satiation;Serum;sex;Signal Transduction;Supplementation;Syndrome;Testing;tool;transmission blocking;Vascular Endothelial Growth Factor Receptor-1;Vascular Endothelial Growth Factors;Volatile Fatty Acids;Woman

PROJECT_TITLE: Lifecycle of obesogenic gender behaviors and cardiometabolic disease in women

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


NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: NARRATIVE: We are proposing PLUS - Phenotyping Large Oncosomes for Ultimate Evaluation of Patients Status as an innovative approach to liquid biopsy for patients with prostate cancer. Our PLUS assay will be a multi-analyte test including the protein and RNA cargo of large extracellular vesicles known as large oncosomes, which are identified in patient plasma and strongly associated with aggressive disease both in the castration resistance and castration sensitive space. Our study is technologically innovative, yet maintains a keen focus on obtaining robust datasets that are obtained from validated protocols run in a CLIA laboratory setting using multiple independent cohorts of cancer patient specimens.

PI_NAMEs: DEMICHELIS, FRANCESCA ;DI VIZIO, DOLORES  (contact);STOTT, SHANNON L

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Address;Androgens;Benchmarking;bioinformatics pipeline;Biological Assay;biomarker identification;Blood;Blood Tests;Cancer Patient;cancer subtypes;Castrate sensitive prostate cancer;Castration;chromatin immunoprecipitation;circulating biomarkers;Circulation;Clinical;clinical translation;cohort;Communities;Complex;Data;Data Set;density;Deposition;deprivation;Development;Disease;DNA Methylation;Elements;Evaluation;Evolution;experience;experimental study;extracellular vesicles;Future;Genomics;Goals;Gold;Hematopoietic Neoplasms;Hormones;In Vitro;inhibitor;innovation;innovative technologies;Laboratories;Lipoproteins;liquid biopsy;Malignant neoplasm of prostate;Malignant Neoplasms;Mass Spectrum Analysis;Metastatic Prostate Cancer;Methods;Microfluidic Microchips;microfluidic technology;Microfluidics;minimally invasive;Molecular;molecular subtypes;neoplastic cell;next generation sequencing;novel;novel marker;Outcome;particle;Patients;Performance;Phenotype;Plasma;Population;pressure;prospective;protein biomarkers;Proteins;Protocols documentation;Quality Control;Resistance;response;RNA;RNA marker;Running;Sampling;Sensitivity and Specificity;Set protein;Signal Transduction;Site;Source;Specimen;Structure of base of prostate;Technology;Testing;Tissues;Transcript;Translating;treatment response;tumor;Tumor-Derived;Validation;Work

PROJECT_TITLE: Clinical Translation of a Large Oncosome-Based Prostate Cancer Blood Test

STUDY_SECTION: MCDC

STUDY_SECTION_NAME: Molecular Cancer Diagnosis and Classification Study Section[MCDC]


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics;Lung;Orphan Drug;Pulmonary Hypertension;Rare Diseases

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Defining the mechanisms underlying the regulation of BMPR2 expression and the role of the epigenetic modifier SIN3a in the lung vascular endothelial cells is critical. Our findings will be of great public health relevance, as we aim to evaluate the effects of SIN3a gene target therapy in the lung vascular cells and right ventricle function. This project supports the NIH’s mission to develop fundamental knowledge and its application to protect and improve human health.

PI_NAMEs: HADRI, LAHOUARIA  (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: Animal Model;Binding;Biological Assay;bone morphogenetic protein receptors;cardiac magnetic resonance imaging;Cell Separation;Cessation of life;Chromatin;Chromatin Structure;Complex;Data;Development;Differentiation and Growth;Disease;DNA;Encapsulated;Endothelial Cells;endothelial dysfunction;Endothelium;Enhancers;Epigenetic Process;epigenetic regulation;Functional disorder;gain of function;Gene Abnormality;Gene Mutation;gene repression;Gene Silencing;gene therapy;Gene Transfer;gene-targeted therapy;Genes;Genetic;Genetic Transcription;Growth;Health;histone methylation;histone modification;Histones;Homeostasis;Homologous Gene;Human;Hypermethylation;Hypoxia;improved;In Vitro;in vivo;insight;Knockout Mice;Knowledge;loss of function;Lung;lung microvascular endothelial cells;Mediating;Messenger RNA;Mission;Modeling;Molecular;Mus;Mutation;nanolipoprotein particles;novel;novel therapeutic intervention;novel therapeutics;overexpression;Pathogenesis;Pathway interactions;Patients;Play;pressure;promoter;Promoter Regions;public health relevance;pulmonary arterial hypertension;pulmonary artery endothelial cell;Pulmonary artery structure;Pulmonary Heart Disease;pulmonary vascular cells;pulmonary vascular remodeling;Pulmonary Vascular Resistance;Rattus;Recombinant adeno-associated virus (rAAV);recruit;Regulation;Research;right ventricular failure;right ventricular remodeling;Right ventricular structure;RNA;Role;Sampling;scaffold;Serotyping;Severities;Signal Pathway;Signal Transduction;Smooth Muscle Myocytes;Stress;Structure of parenchyma of lung;targeted treatment;Testing;Therapeutic Effect;tool;Transcriptional Activation;Treatment Efficacy;United States National Institutes of Health;Validation;Vascular Diseases;Vascular remodeling

PROJECT_TITLE: Role of Epigenetic Regulator SIN3a in Pulmonary Endothelial Cells

STUDY_SECTION: RIBT

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Genetics;Infectious Diseases;Machine Learning and Artificial Intelligence

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: NARRATIVE The Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) can hijack the normal operations of human cells, which makes it especially dangerous. It encodes a set of nonstructural proteins (nsp) to protect its RNA genome from host degradation and immune restriction. Our studies will combine biochemical, structural, cellular, and genomic approaches to address fundamental questions related to RNA modification, host immune restriction, viral growth and pathogenesis, and develop new molecular tools to collectively inform new COVID- 19 treatments and protect ourselves against future coronaviral infections.

PI_NAMEs: GUPTA, YOGESH K (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;Ablation;ACE2;Active Sites;Address;Amino Acids;analog;Architecture;Artificial Intelligence;Bacterial Artificial Chromosomes;betacoronavirus;Binding;Biochemical;Biological Assay;Biology;biophysical analysis;Biophysics;Cells;Chiroptera;combinatorial;Communication;Complex;convolutional neural network;Coronavirus;COVID-19;COVID-19 therapeutics;COVID-19 treatment;Crystallization;Cultured Cells;Dangerousness;Data;Disease;Distant;drug candidate;drug repurposing;Economics;effective therapy;Enzymes;epidemiologic data;Future;genetic approach;Genetic Transcription;Genome;Genomic approach;Growth;Health;Human;Immune;Immune Evasion;Immune response;Immune system;improved;in vitro testing;in vivo;Individual;Infection;Innate Immune Response;innovation;Invaded;Investigation;K-18 conjugate;Length;Libraries;Life Cycle Stages;Maintenance;Maps;Messenger RNA;Methods;methyl group;Methylation;Modeling;Modification;Molecular;Molecular Conformation;Morbidity - disease rate;mortality;mouse model;Mus;Mutation;Nature;Nonstructural Protein;novel;novel therapeutic intervention;Nucleoproteins;Nucleotides;operation;Organism;pandemic disease;Paper;Pathogenesis;programs;Property;protein complex;Proteins;Publishing;Recombinants;Recording of previous events;Reporting;Research;reverse genetics;RNA;RNA Binding;RNA Caps;RNA chemical synthesis;RNA Degradation;RNA Folding;RNA methylation;RNA Processing;RNA Viruses;S-Adenosylhomocysteine;S-Adenosylmethionine;SARS coronavirus;SARS-CoV-2 infection;SARS-CoV-2 inhibitor;screening;Series;small molecule;small molecule libraries;Solid;Specificity;stem;structural determinants;Structure;Structure-Activity Relationship;Surface;Technology;Testing;therapeutic target;Time;tool;transcriptomics;Translations;Untranslated Regions;vaccine development;Viral;Viral Genome;Viral Pathogenesis;Viral Proteins;viral RNA;Virion;Virus;Virus Assembly;Virus Diseases;Virus Replication;X-Ray Crystallography

PROJECT_TITLE: Mechanism-based targeting of the RNA processing machinery of SARS-CoV-2-


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Contraception/Reproduction;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Maternal Health;Maternal Morbidity and Mortality;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Pregnancy;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health;Substance Misuse;Substance Misuse Prevention;Women's Health Research

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

PHR: Expansion of Clinical Trials Network Research Capacity to Address Overdose Mortality in Pregnant and Post-Partum Individuals with OUD PROJECT NARRATIVE This expansion project will encompass the following four projects, aimed at opioid overdose prevention, learning about barriers and facilitators regarding treatment and research engagement in pregnant and post-partum individuals (PPI) with OUD, especially PPI of color and those living in rural areas. The IMPROVE expansion project teams will work with the IMPROVE COE Implementation Hub to disseminate any products generated, which will focus on recruitment, retention, and engagement of pregnant/postpartum women with OUD. Project 1: Personally-Tailored Opioid-overdose and Medication for opioid use disorder (MOUD) Education (TOME) for pregnant and postpartum persons in MOUD: A pilot randomized trial (TOME trial) This study plans to evaluate the benefit of personally-tailored opioid overdose and medication for opioid use disorder education in pregnant and post-partum individuals receiving medication for opioid use disorder. Approximately 120 PP will be randomized in a 1:1 ratio to TOME or control balancing on site. TOME participants will receive a 15-minute intervention in which a trained research staff member reviews personal feedback reports with the recipient to provide information on the items missed on the opioid overdose (OOD) and MOUD knowledge assessment. Control participants will receive SAMHSA handouts about OOD and MOUD. Project 2: Successful Recruitment and Retention in a Randomized Controlled Trial of Pregnant People with Opioid Use Disorder (SUCCESS STUDY) This study plans to identify currents strategies, facilitators and challenges in recruitment and retention among sites in the MOMs trial. This project will conduct surveys, focus groups and interviews with research staff and individuals currently enrolled in the study. This project will develop a manual with recommendations for strategies and approach for trials to recruit and retain PP with OUD in RCTs. Project 3: Promoting Research with Mothers receiving OUD Treatment; a focus on Equity (PRoMOTE) This study plans to understand patient and provider perspectives and key facilitators and barriers to treatment engagement for women in color and living in rural areas. The study will invite patients and providers to participate in surveys and focus interviews; the patient interviews will be completed by mothers in recovery (trained and mentored on interviewing skills) who have expertise in interviewing women of color and women living in rural areas with SUD. The studies will seek to understand the needs of pregnant women who use opioids (including fentanyl) from diverse communities that include communities with differing laws regarding reproductive health. The data will assist in future outreach and engagement in MOUD. Project 4: Improved Messaging Strategies for MOUD for Underserved Populations of Pregnant and Postpartum Individuals with OUD. This project plans to develop innovative and meaningful education/messaging strategies regarding (1) addiction disease & NOWS, (2) the role of medications in the management of OUD and overdose prevention, (3) stigma and health system mistrust, and (4) PP persons rights to treatment. This project plans to involve researchers, patients, and community advisors to develop products specific to the target population (Hispanic, Black, and Native PP women, and those living in rural areas).

PI_NAMEs: WINHUSEN, T JOHN (contact)

PROGRAM_OFFICER_NAME: DOBBINS, RONALD

PROJECT_TERMS: addiction;Address;Adherence;American;barrier to care;Black race;Buprenorphine;Cessation of life;Characteristics;clinical research site;Clinical Trials;Clinical Trials Network;Color;Communities;Data;Disease;Drug usage;Education;Elements;Enrollment;Environment;Equity;ethnic difference;ethnic minority population;Feedback;Fentanyl;Focus Groups;Funding;Future;Health;Health system;Hispanic;improved;Individual;innovation;internalized stigma;Intervention;Interview;Knowledge;Laws;Learning;Low Birth Weight Infant;Manuals;Maternal Mortality;medication for opioid use disorder;member;Mentors;Methadone;Methods;mortality;Mothers;National Institute of Drug Abuse;Ohio;Opioid;opioid overdose;opioid use;opioid use disorder;outreach;Overdose;overdose death;overdose prevention;Participant;Patients;people of color;Persons;Pharmaceutical Preparations;Postpartum Period;Postpartum Women;Pregnancy;Pregnancy Outcome;pregnancy related death;pregnant;Pregnant Women;Premature Birth;Prenatal care;prescription opioid;Procedures;Provider;racial difference;racial minority;Randomized;randomized trial;Randomized, Controlled Trials;Recommendation;Recovery;recruit;Relapse;Reporting;Reproductive Health;Request for Proposals;Research;Research Methodology;Research Personnel;Research Training;Resources;Right to Treatments;Role;rural area;Rural Population;Site;skills;social stigma;Surveys;Target Populations;tool;Training;treatment adherence;trend;trial enrollment;Underserved Population;United States;United States Substance Abuse and Mental Health Services Administration;Visit;Woman;women of color;Work

PROJECT_TITLE: IMPROVE


ADMINISTERING_IC: HD

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

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Narrative The ovarian reserve is a finite and precious pool of early oocytes established in the fetal ovary and that regulates a woman’s overall health and fertility. We have discovered that TAF4b promotes precise development of the mouse ovarian reserve and TAF4b-deficient mice undergo many of the hallmarks of premature ovarian aging including defective meiosis I, increased primordial follicle attrition, elevated gonadotropins and female infertility. By elucidating the molecular mechanisms of TAF4b in the regulation of the establishment of the ovarian follicle reserve in the mouse, we will increase our fundamental understanding of the mechanisms that regulate the establishment of the human ovarian reserve.

PI_NAMEs: FREIMAN, RICHARD NEIL (contact)

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: Acceleration;Address;Adult;Affect;Anterior;Biological;Cardiovascular system;Cells;chemotherapy;Chromatin;chromatin modification;Chronology;Clinical;Complex;Couples;Data;Development;Diagnosis;DNA Sequence Alteration;DNA-Protein Interaction;Embryo;Endocrine;Ensure;Epigenetic Process;epigenetic regulation;epigenome;Estrus;Etiology;Event;experience;Female;female fertility;Female infertility;Fertility;fertility preservation;fetal;Fetal Development;Follicle Stimulating Hormone;Fragile X Syndrome;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;Genome;Genomics;Germ Cells;girls;Gonadotropins;Health;Heterogeneity;Histone H3;histone modification;Human;Impaired cognition;improved;Infertility;innovation;insight;Knowledge;Life;life span;Link;Location;Lysine;Maintenance;Mammals;Maps;Measures;Meiosis;Meiotic Prophase I;Modification;Molecular;Molecular Profiling;Monitor;mouse development;mouse model;Multiprotein Complexes;Mus;Mutagens;Nature;Newborn Infant;novel;novel marker;oocyte quality;Oocytes;Osteoporosis;Outcome;Ovarian;Ovarian Follicle;ovarian reserve;Ovary;Pathologic;Pathway interactions;Patients;Population;Population Heterogeneity;postnatal;Predisposition;Premature Menopause;Premature Ovarian Failure;preservation;primary outcome;primary ovarian insufficiency;Primordial Follicle;Process;Production;programs;Proteins;Regulation;Risk;RNA Polymerase II;Role;Serum;single-cell RNA sequencing;TAF1 gene;TATA-Binding Protein Associated Factors;TATA-Box Binding Protein;Testing;Time;Toxic Environmental Substances;transcription factor;Transcription Factor TFIID;Transcriptional Regulation;transcriptome;Turner's Syndrome;United States;Woman;Work

PROJECT_TITLE: Regulating Establishment of the Mammalian Ovarian Reserve

STUDY_SECTION: CMIR

STUDY_SECTION_NAME: Cellular, Molecular and Integrative Reproduction Study Section[CMIR]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

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

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Multimodal signals, such as the integrated face and voice of an engaging caregiver, draw attention to and facilitate processing of communicative cues that occur across modalities, particularly beneficial when language processing is difficult. By leveraging the continuum of multi modality that naturally occurs in the ecologically-valid communicative signals of infant-directed speech and song, the current project investigates mechanisms (specific multimodal cues), moderators {diagnosis, expressive language), and communicative contexts (infant-directed speech and song) that adaptively drive patterns of social visual attention (e.g., mouth-looking) for language development in autism. By combining new data collection with a large extant longitudinal database of autistic infants and toddlers over the first two years of life, findings will identify underlying multimodal communication mechanisms, developmental windows of opportunity, and individually-tailored, actionable targets for early language intervention using multimodal infant-directed communication.

PI_NAMEs: EDWARDS, LAURA ;LENSE, MIRIAM  (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Affect;Attention;Auditory;autism spectrum disorder;autistic;autistic children;Automobile Driving;Caregivers;Child;cohort;Communication;Communication difficulty;Complement;Cues;Data;Data Collection;Data Set;design;Development;Diagnosis;Diagnostic;Early Intervention;Environment;Exhibits;Eye;Face;Family;Grain;Growth;Impairment;improved;Individual;individuals with autism spectrum disorder;Infant;Infant Development;Intervention;intervention delivery;Language;Language Delays;Language Development;language outcome;language processing;Life;Linguistics;Link;longitudinal database;Measures;Modality;Modeling;multimodality;multisensory;Natural Increases;novel;Oral cavity;Outcome;outcome prediction;Pattern;Periodicity;phrases;Population;Production;prospective;Research;Role;Sampling;sensory integration;signal processing;Signal Transduction;skills;social;Speech;speech processing;Testing;therapy development;Time;Toddler;verbal;Visual;Visual attention;visual tracking;Voice

PROJECT_TITLE: Social Visual Attention and Language Development in Autism: Leveraging Infant-Directed Speech and Song to Identify Multimodal Mechanisms of Communication

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Climate-Related Exposures and Conditions;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Lung;Lung Cancer;Precision Medicine;Prevention;Social Determinants of Health;Tobacco;Tobacco Smoke and Health

ORG_CITY: ATLANTA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Air pollution is a known environmental risk factor for lung cancer, but the detailed mechanisms driving air pollution-induced lung carcinogenesis are not yet fully understood. To address these critical gaps, I propose this F99/K00 study to investigate the underlying molecular signatures and pathways using novel multi-omics integration across genomics, proteomics, and metabolomics in my F99 training. Transitioning to my K00 phase, I will focus on developing omics-based risk prediction models to enhance lung cancer risk stratification by smoking status, a crucial step toward identifying high-risk individuals.

PI_NAMEs: TANG, ZIYIN  (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Address;aged;Air Pollutants;Air Pollution;ambient air pollution;Amino Acids;anti-cancer research;Automobile Driving;Biological;cancer classification;cancer prevention;cancer risk;carcinogenesis;Carcinogens;case control;Comprehensive Cancer Center;Cysteine;Data Set;Deposition;Development;Diagnosis;Disease;Early Diagnosis;Energy Metabolism;environment related cancer;Environmental Exposure;Environmental Risk Factor;Etiology;Event;Exposure to;falls;Foundations;Future;Genomics;Guidelines;Health;high dimensionality;high risk;high risk population;Human;Incidence;Individual;indoor particulate matter;Inflammation;innovation;insight;Institution;International Agency for Research on Cancer;Investigation;Learning;Light;Link;low dose computed tomography;lung cancer screening;lung carcinogenesis;Malignant neoplasm of lung;Mediating;Mediation;Mediator;Mentors;metabolomics;Methionine;Modality;Molecular;Molecular Profiling;mortality;multiple omics;never smoker;novel;Outcome;Oxidative Stress;Pathway interactions;Peptide Metabolism;Peptides;Performance;Phase;Population;post-doctoral training;Preventive;Process;prospective;Proteins;Proteomics;Recommendation;Research Institute;Resources;Respiratory System;response;Risk;risk prediction;risk prediction model;risk stratification;Role;screening;Signal Transduction;Single Nucleotide Polymorphism;Smoker;Smoking;Smoking History;Smoking Status;study population;Survival Rate;systematic review;Technology;Therapeutic;tool;Toxic effect;Training;Tryptophan;Tyrosine;urea cycle

PROJECT_TITLE: Investigating the molecular signatures and pathways indicative of air pollution toxicity in lung carcinogenesis using single- and multi-omics analyses of genomics, proteomics, and metabolomics


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Chronic Pain;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Pain Research;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Social Determinants of Health;Substance Misuse

ORG_NAME: GEORGIA STATE UNIVERSITY

PHR: PROJECT NARRATIVE Staying in the neonatal intensive care unit (NICU) can have lasting effects on the brain and behavior, including increasing the risk for substance use disorders. Here we will develop a better rat model of the NICU experience to elucidate how this early adversity changes social and cannabis motivation, as well as causes structural and molecular changes in the medial prefrontal cortex, a key part of the reward circuit. Successful development of this NICU model and the hypothesis-generating activities in this grant will launch future proposals delineating mechanisms by which a common early adverse experience changes reward circuitry and increases adolescent drug misuse.

PI_NAMEs: BANGASSER, DEBRA A (contact);MURPHY, ANNE Z

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: 3-Dimensional;Absence of pain sensation;addiction;Address;Admission activity;Adolescence;Adolescent;Adult;Adverse event;Advisory Committees;Affect;Behavior;Behavioral;behavioral phenotyping;behavioral study;Biological Assay;Birth;Brain;Cannabis;Child Rearing;Clinical;clinically relevant;comorbidity;comparison control;Data;Data Set;design;Development;Diffusion Magnetic Resonance Imaging;DNA Methylation;DNA sequencing;drug misuse;Drug usage;early life adversity;Elements;Environmental Risk Factor;epigenome;experience;Family;Female;Fiber;Funding;Future;Grant;gray matter;high risk;Home;Human;human imaging;illicit drug use;Image;imaging study;improved;infancy;Infant;Leadership;Life;Link;longitudinal design;low socioeconomic status;Magnetic Resonance Imaging;male;Male Adolescents;marijuana use;maternal separation;Medial;Methylation;Modeling;Molecular;motivated behavior;Motivation;multidisciplinary;Neonatal Intensive Care Units;Neurobiology;neuroimaging;novel;Pain;Periodicals;Persons;Pharmaceutical Preparations;Play;Population;preclinical study;Prefrontal Cortex;Pregnancy;premature;Premature Birth;prenatal stress;primary caregiver;Procedures;Rattus;Research Design;Resources;reward circuitry;Rewards;Risk;Risk Factors;Rodent;Sampling;Self Administration;social;Social Behavior;Social Change;Social isolation;socioenvironmental factor;Stress;stressor;structural imaging;Structure;substance misuse;Substance Use Disorder;Testing;Tetrahydrocannabinol;translational model;Translations;United States

PROJECT_TITLE: Early life pain and its modulation by socioenvironmental factors: Implications for substance misuse

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 CEM-N (M1)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Estrogen;Mental Health;Mental Illness;Neurosciences;Social Determinants of Health;Women's Health Research

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

PHR: Contact PD/PI: Kim, Chung Sub Public Health Relevance Narrative Social stress in humans increases the risk of developing depression and anxiety. Hippocampal dendritic HCN channels play in regulating stress coping and individual differences in both sexes. The results will provide important insights into the sex differences in stress coping and individual variations to social defeat.

PI_NAMEs: KIM, CHUNG SUB  (contact)

PROGRAM_OFFICER_NAME: HUPALO, SOFIYA

PROJECT_TERMS: Acute;Affect;Aggressive behavior;Anhedonia;Anxiety;Area;Behavioral;behavioral response;Brain;bullying;Castration;Cations;Cells;cellular imaging;Chronic;Chronic stress;coping;Cyclic Nucleotides;Data;Dendrites;depressive symptoms;Distal;Dorsal;Emotional;Estradiol;Estrogens;Exhibits;experience;Exposure to;Female;Fiber;Freezing;Fright;Gender;gender difference;Genes;Goals;HCN1 gene;HCN2 protein;Hippocampus;Human;hyperpolarization-activated cation channel;in vivo calcium imaging;Individual;Individual Differences;individual response;individual variation;Inequality;insight;Life;Link;Major Depressive Disorder;male;maternal aggression;Mediating;men;Mental Depression;Mental disorders;Mental Health;Microscopy;Molecular;mouse model;mRNA Expression;Mus;Neurons;new therapeutic target;novel;Ovariectomy;overexpression;patch clamp;Patients;Persons;Photometry;Physiological;Play;Population;Post-Traumatic Stress Disorders;pre-clinical;pre-clinical research;Predisposition;protein expression;Protein Isoforms;psychologic;Psychosocial Stress;public health relevance;Reproductive Periods;resilience;response;Risk;Rodent Model;Role;severe mental illness;sex;Sex Differences;sex variable;sexual dimorphism;social;social defeat;Social Interaction;social stress;Stress;Stress and Coping;stress related disorder;Synapses;Synaptic Transmission;Testing;Woman

PROJECT_TITLE: Role of hippocampal HCN Channels in social avoidance

STUDY_SECTION: PMDA

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


NIH_SPENDING_CATS: Cancer;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Uterine Cancer;Women's Health Research

ORG_CITY: MANHASSET

ORG_NAME: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH

PHR: PROJECT NARRATIVE There are significant and persistent racial and ethnic disparities in incidence and mortality for endometrial cancer. We propose to develop and validate statistical risk prediction models for endometrial cancer leveraging the racial and ethnic diversity of the All of Us Research Program cohort with the goal of creating better strategies for early detection across diverse populations. Our innovative modeling approach integrates the burden of rare deleterious genetic variation, epidemiological risk factors and socio-environmental indices causally associated with endometrial cancer health disparities.

PI_NAMEs: CHAMBWE, NYASHA  (contact)

PROGRAM_OFFICER_NAME: WALLACE, TIFFANY A

PROJECT_TERMS: Address;advanced disease;All of Us Research Program;Alleles;Assessment tool;Automobile Driving;autosome;biobank;black women;Body mass index;cancer health disparity;cancer invasiveness;cancer predisposition;cancer risk;cancer subtypes;Candidate Disease Gene;case control;Catalogs;Code;cohort;Complex;cost;Cox Proportional Hazards Models;Data;Data Set;Death Rate;Detection;detection method;Development;Diabetes Mellitus;Diagnosis;Diagnostic Procedure;Disease;Disparity;Early Diagnosis;Endometrial;Endometrial Carcinoma;Environment;Environmental Risk Factor;Epidemiology;Estrogens;ethnic disparity;ethnic diversity;Ethnic Origin;Ethnic Population;Etiology;Gene Silencing;Genes;Genetic;genetic information;Genetic Models;Genetic Predisposition to Disease;Genetic Screening;Genetic Variation;genome sequencing;Germ Lines;Goals;Hereditary Nonpolyposis Colorectal Neoplasms;high risk;Histologic;homologous recombination deficiency;improved;improved outcome;Incidence;indexing;Individual;Inherited;innovation;insight;Intervention;Knowledge;lifestyle factors;lifetime risk;Link;Malignant Neoplasms;Metastatic breast cancer;Mismatch Repair;MLH1 gene;Modeling;Molecular;molecular marker;mortality;MSH2 gene;Multiple Hamartoma Syndrome;Mutation;non-genetic;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Outcome;Pathogenicity;Pathway interactions;Patient-Focused Outcomes;Patients;Penetrance;Performance;PMS2 gene;Polycystic Ovary Syndrome;polygenic risk score;Population;Population Heterogeneity;predictive modeling;Predisposition;Prevention strategy;Proteins;PTEN gene;Public Health;Publishing;Race;racial disparity;racial diversity;racial population;rare variant;Recording of previous events;Research;Risk;Risk Assessment;Risk Factors;risk prediction model;risk stratification;Sampling;screening;Screening for Endometrial Cancer;social;social culture;Social Environment;social factors;Survival Rate;Symptoms;Syndrome;Testing;Time;Training;tumorigenesis;Underrepresented Populations;Validation;Variant;whole genome

PROJECT_TITLE: Development of integrated risk models of genetic and non-genetic risk factors in endometrial cancer across diverse ancestries

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BTC-Y (55)]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Chronic Liver Disease and Cirrhosis;Colorectal Cancer;Digestive Diseases;Liver Disease;Women's Health Research

PHR: PROJECT NARRATIVE Despite advances in cancer treatment, metastatic disease is almost always fatal. In addition, tumor cells can spread early to distant organs, survive initial treatment, and lie dormant for years before reactivating to produce a detectable tumor. This study will investigate the tumor cell-intrinsic and extrinsic factors that drive drug resistance and metastasis.

PI_NAMEs: PRIMEAUX, MARK  (contact)

PROJECT_TERMS: Address;Adult;Advanced Malignant Neoplasm;Affect;anti-cancer research;Area;Automobile Driving;Binding;Biochemistry;Bioinformatics;Blood Vessels;Bone Marrow;breast cancer metastasis;Breast Cancer Model;cancer cell;Cancer Model;cancer therapy;career;CD44 gene;Cell Cycle Arrest;Cells;Cessation of life;Characteristics;Chemoresistance;claudin-1 protein;Colorectal Cancer;colorectal cancer metastasis;Complex;Data;Development;Dimensions;Disease;Distant;Drug resistance;Elements;Environment;Ephrins;Epigenetic Process;Foundations;Future;Genetic;genetic manipulation;Goals;Hepatic;Hepatic Stellate Cell;Immune Evasion;Immunocompetent;Immunology;in silico;In Vitro;in vitro Model;in vivo;in vivo Model;innovation;insight;Letters;Liver;Liver diseases;Malignant Breast Neoplasm;Malignant Neoplasms;Metastatic Neoplasm to the Liver;Modeling;Molecular;mouse model;Mutate;Mutation;Neoplasm Metastasis;neoplastic cell;non-alcoholic fatty liver disease;novel;Oncogenic;Organ;Organoids;overexpression;patient prognosis;Patients;Pattern;Phase;Population;post-doctoral training;Postdoctoral Fellow;Preparation;Primary Neoplasm;Process;Prognosis;protein protein interaction;Proteins;Proto-Oncogene Proteins c-akt;Publishing;receptor;Receptor Protein-Tyrosine Kinases;Relapse;Reporting;Research;Research Personnel;Resistance;Resolution;Role;Signal Pathway;Signal Transduction;skills;Slice;stemness;Systemic Therapy;T-Lymphocyte;Techniques;Testing;Therapeutic;Tissues;Training;Training Programs;transcriptome sequencing;tumor;tumor immunology;tumor initiation;Tumor Promotion;Tumor Tissue;tumor-immune system interactions;tumorigenesis;Validation;Work

PROJECT_TITLE: Tumor-cell intrinsic and extrinsic determinants of drug resistance and metastasis

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RTRB-U (M1)]


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Cancer;Digestive Diseases;Liver Disease;Microbiome;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: Narrative We aim to deeply characterize the microbes present in the pancreatic cancer microenvironment from spatial and functional perspective. To this end, we will use a combination of human tissue- based analysis, mouse models of pancreatic cancer and liver metastasis, as well as organoid and barcoding-based microbial tracking studies. The results of the studies proposed will be crucial to inform the development of novel microbial modulation strategies to tackle this deadly disease.

PI_NAMEs: MCALLISTER, FLORENCIA  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Ablation;Affect;Bacteria;Bar Codes;biobank;cancer cell;Cancer Etiology;cell type;Cells;Cessation of life;Clinic;Coculture Techniques;Collaborations;Colorectal Neoplasms;Data;Development;Diagnosis;Disease;Distant;DNA;DNA sequencing;Excision;Exhibits;experimental study;Exposure to;fecal transplantation;Genetically Engineered Mouse;germ free condition;Germ-Line Mutation;Goals;Growth;gut microbiota;Home;Homing;Host Defense;Human;human tissue;Image;Immune;Immunosuppression;Implant;improved outcome;In Vitro;in vivo;Ink;innovation;Knowledge;Learning;Link;Liver;Location;Long-Term Survivors;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Metastatic Neoplasm to the Liver;metastatic process;Methodology;Microbe;microbial;microbial based therapy;microbial composition;microbial host;Minority;Molecular;mouse model;multiplexed imaging;Mus;Neoplasm Metastasis;new therapeutic target;non-genetic;novel;Organoids;Outcome;Pancreas;pancreatic cancer model;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic neoplasm;Patient-Focused Outcomes;Patients;Pattern;Preventive;Primary Neoplasm;Process;Reporting;Resected;Role;Scheme;Science;screening;Site;Somatic Mutation;success;Survival Rate;Testing;Time;transcriptomics;Translating;tumor;tumor growth;tumor microenvironment;tumorigenesis

PROJECT_TITLE: Interrogating the Spatial and Functional Relevance of Microbes in Pancreatic Cancer and Metastasis

STUDY_SECTION: THI

STUDY_SECTION_NAME: Tumor Host Interactions Study Section[THI]


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Estrogen;Genetics;Neurosciences;Rare Diseases;Women's Health Research

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Hormone receptor expression and signaling are hypothesized to play varying and important pathologic roles in central nervous system (CNS) tumors, most notably in meningiomas, the most common primary intercranial tumors, and glioblastomas, the most malignant primary brain tumors in adults. However, the biochemical and gene expression mechanisms underlying sex-specificity and hormone receptor signaling in these tumors remain largely unknown. To address these limitations, this project will investigate the role of female sex hormones in driving progesterone receptor expression and signaling in meningiomas, and will use large-scale proteomics to shed light on hormone receptor signaling axes in glioblastomas in order to identify novel therapeutic targets in these devastating CNS cancers.

PI_NAMEs: DWYER CADY, MARTHA ADDISON (contact)

PROJECT_TERMS: Address;Adult;Androgen Receptor;Automobile Driving;Binding;biobank;Biochemical;Biochemistry;cancer type;Cell Culture Techniques;Cell Line;Cell Nucleus;Cell Proliferation;Central Nervous System Neoplasms;ChIP-seq;clinically relevant;cofactor;Combined Modality Therapy;Cytoplasm;Data;data integration;Data Set;Development;Dissociation;DNA Damage;Dose;Elements;Endometrial Carcinoma;Estrogen Receptors;Estrogens;experimental study;Feedback;Female;female sex hormone;gain of function;Gene Expression;Genes;Genetic;genetic corepressor;Genetic Transcription;Glioblastoma;Gonadal Steroid Hormones;Growth;Hormonal;hormonal signals;Hormone Receptor;hormone therapy;Hormones;Human;in vitro Model;in vivo;in vivo Model;Incidence;Individual;inhibitor;insight;Intracranial Neoplasms;IRS2 gene;knock-down;Knowledge;Ligand Binding;Ligands;Link;loss of function;Luciferases;male;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of brain;Malignant neoplasm of central nervous system;Malignant Neoplasms;MAP Kinase Gene;Mass Spectrum Analysis;Mediator;Membrane;meningioma;Metadata;Modeling;Molecular;Mus;new therapeutic target;NF-kappa B;novel;Nuclear;Pathologic;Pathology;Pathway interactions;Patients;Pattern;Phenotype;phosphoproteomics;Phosphorylation;Play;Post-Translational Protein Processing;Postdoctoral Fellow;Pre-Clinical Model;Primary Brain Neoplasms;Progesterone;progesterone receptor B;Progesterone Receptors;Progestins;prognostic;Proliferating;promoter;Proteins;Proteomics;receptor;receptor expression;Receptor Signaling;Regulation;Reporter;Research;response;Role;Serum;sex;Signal Pathway;Signal Transduction;small molecule;Specificity;SRC gene;Synthetic Progestogens;System;targeted treatment;Techniques;Testing;Therapeutic;Therapeutic Intervention;TNFSF11 gene;Transcriptional Activation;translational potential;tumor;tumor growth;Tumor Pathology;tumorigenesis;tumorigenic;Up-Regulation;Validation;Women's Role;Work;Xenograft procedure

PROJECT_TITLE: Understanding expression and signaling of sex hormone receptors in brain cancers


NIH_SPENDING_CATS: Genetics

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: The growth factors and transcriptional activators that specify monocyte/macrophage (MF) differentiation into diverse types of monocytes and tissue-resident MFs have largely been identified. In contrast, the impact of environmental signals – particularly that of endogenous metabolites – on MF differentiation and function remains essentially unexplored. In this project we will characterize the impact of intracellular trafficking of heme, a vital metabolite, in MF biology and its role in homeostasis and disease.

PI_NAMEs: NAGY, LASZLO ;SAEZ, ENRIQUE  (contact)

PROGRAM_OFFICER_NAME: ROY, CINDY

PROJECT_TERMS: Acute;Adipocytes;Affect;Attention;Automobile Driving;BACH1 gene;Binding;Biological Assay;Biology;Bone Marrow;Bone Marrow Transplantation;Cell Nucleus;Cell Physiology;Cells;Chemicals;Chromatin;CSF1 gene;cytotoxic;Data;Defect;Development;Direct Lytic Factors;Disease;Disease Resistance;Dose;Environmental Impact;Erythrocytes;extracellular;Fatty acid glycerol esters;fitness;gain of function;Gene Expression;Gene Expression Regulation;Genetic;Genetic Transcription;Genomics;Growth Factor;Heme;Hemoglobin;Homeostasis;IL6 gene;in vivo;Infiltration;Inflammation;Inflammatory;Injury;insight;Intestines;Iron;Knockout Mice;Kupffer Cells;Life;loss of function;Macrophage;Measures;Mediating;Mediator;Metabolic;Metabolic dysfunction;Mitochondria;Modeling;Molecular;Molecular Analysis;Molecular Chaperones;Monitor;monocyte;mortality;mouse model;Mus;Muscle;Mutant Strains Mice;Myelogenous;Myeloid Cells;Myeloid Progenitor Cells;Nuclear;Nurses;Pathologic;Pathway interactions;Phenotype;Physiology;Play;Population;Population Heterogeneity;Population Study;Process;Progesterone Receptors;Proteins;regenerative;repaired;response;Role;senescence;Signal Pathway;Signal Transduction;Specific qualifier value;Splenic Red Pulp;Sterility;Stimulus;Stress;System;systemic inflammatory response;tissue repair;Tissues;tool;trafficking;Transcription Coactivator;transcription factor;Transcription Repressor

PROJECT_TITLE: Intracellular trafficking of the essential signaling metabolite heme in myeloid cells: impact on physiology and disease

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Social Determinants of Health;Women's Health Research

ORG_CITY: WORCESTER

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Depression and poverty are linked together in an intractable syndemic affecting millions of people around the world. Poverty is a major cause of depression, while depression significantly reduces economic productivity. Integrated intervention approaches that seek to interrupt the cycle of poverty and depression have not been tested. Innovative science is required to move forward in this area: a diversified scientific workforce is key to scientific innovation. This application describes a Diversity Supplement application that will prepare a diversity candidate, the first in her family to attend college, for a career in global mental health research.

PI_NAMEs: KARASZ, ALISON  (contact);TOFAIL, FAHMIDA

PROGRAM_OFFICER_NAME: VEDHAM, VIDYA

PROJECT_TERMS: Address;Affect;Area;Bangladesh;career;college;design;disability;Economics;empowerment;Epidemic;Family;Fellowship;fighting;Funding;graduate school;hands on research;improved;innovation;Interruption;Intervention;Link;low and middle-income countries;Low income;Mental Depression;Mental disorders;Mental Health;National Institute of Mental Health;pandemic disease;Pathway interactions;Persons;Play;Policy Maker;Poverty;poverty alleviation;Productivity;Psychologist;Randomized, Controlled Trials;Research;Research Activity;Research Personnel;Role;Rural;Science;Social Network;syndemic;Testing;Traineeship;Training;Training Activity;Training Programs;treatment effect;uptake;Woman;Work

PROJECT_TITLE: ASHA Bangladesh--An Integrated Intervention to Address Depression in Low Income Rural Women


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biotechnology;Genetics;Neurosciences;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Rehabilitation;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: La Jolla

ORG_NAME: SALK INSTITUTE FOR BIOLOGICAL STUDIES

PHR: Narrative: Public Health Relevance Sensory afferent feedback plays a critical role in controlling movement, however, we still know very little about the central transmission pathways and how they intersect with spinal motor system. Studies in this proposal will dissect the functional organization of the sensorimotor circuitry in the spinal cord, in order to better understand the control systems that regulate movement and to develop new approaches for treating spinal motor disorders and spinal cord injury, as well as neuropathic pain and chronic itch.

PI_NAMEs: GOULDING, MARTYN D (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Animals;Behavior;Behavioral Assay;cell type;Cells;chronic itch;Dorsal;Feedback;Forelimb;Genetic;genetic manipulation;Goals;grasp;Human;improved;insight;Interneurons;Light;Limb structure;Maps;Mechanics;Modeling;Motor;Motor Activity;motor behavior;motor control;motor disorder;mouse genetics;Movement;Neurons;novel strategies;optogenetics;painful neuropathy;Pathway interactions;Play;Population;Pruritus;public health relevance;Reflex action;Reporter;Role;Running;Sensory;sensory feedback;Spinal;Spinal Cord;Spinal cord injury;spinal reflex;Synapses;System;Touch sensation;transmission process;Walking;Withdrawal

PROJECT_TITLE: Spinal circuits for mechanical itch and light touch


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: SANTA CRUZ

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: Directed evolution has proven to be a valuable technique for adapting enzymes to do elaborate chemistries that would otherwise be synthetically challenging. A major bottleneck to evaluating the hundreds to thousands of individually mutated library members involves the screening of products using colorimetric reporter or bioactivity assays, or time-consuming chromatography-based analyses on the experiments themselves. We propose to combine our respective strengths in biochemistry and mass spectrometry to develop a sensitive, accurate high throughput mass spectrometry based workflow to expedite the screening of a directed evolution library without the reliance on chromatography techniques in order to identify significant biocatalytic transformations.

PI_NAMEs: SANCHEZ, LAURA MARGARET (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Acids;Acoustics;Agonist;alpha ketoglutarate;Amino Acid Substitution;analog;Analytical Chemistry;antagonist;assay development;Automation;Biochemical;Biochemical Reaction;Biochemistry;Biological Assay;Biology;Biotechnology;Cells;Chemicals;Chemistry;Chromatography;Confounding Factors (Epidemiology);Constitution;Consumption;Coupled;Cyclization;Deposition;Detection;Development;Dioxygenases;directed differentiation;Directed Molecular Evolution;Enzymes;Escherichia coli;Evolution;experimental study;Family;Foundations;Future;Gas Chromatography;Generations;Genes;genomic locus;Glutamate Receptor;high dimensionality;High Pressure Liquid Chromatography;Homologous Gene;Image;imaging software;Individual;Industrialization;Industry;Infrastructure;innovation;ion mobility;Isomerism;Kainic Acid;Laboratories;Lactones;Lead;Libraries;Mass Fragmentography;mass spectrometric imaging;Mass Spectrum Analysis;Measurement;member;Metabolic Biotransformation;Methodology;microbial;microbial colonization;Molecular Weight;mutant;Mutate;Mutation;Natural product discovery;Nature;Neurotoxins;non-Native;novel;Nuclear Magnetic Resonance;Outcome;Polymerase Chain Reaction;Process;Production;Proteins;Pyrrolidines;Rapid screening;Reporter;Research;Research Personnel;Sampling;screening;Screening Result;Site;small molecule;Specificity;Spectrometry;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Spottings;Statistical Data Interpretation;Synthesis Chemistry;System;tandem mass spectrometry;Techniques;Technology;Therapeutic;Time;tool;Variant;vector;Work

PROJECT_TITLE: Development of a high throughput platform for screening directed evolution libraries

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: DETROIT

ORG_NAME: JOHN D DINGELL VA MEDICAL CENTER

PHR: Central sleep apnea (CSA) is common in patients with heart failure and those using opioid analgesics. Unfortunately, effective treatment of central apnea remains elusive, pressure therapy given the modest efficiency of positive airway pressure therapy. The focus of this proposal is to identify mechanistic pathways to guide future therapeutic interventions for central sleep apnea based on the strong premise that multi-modality therapy will normalize respiration and hence mitigate adverse long-term consequences of CSA. Our proposed studies will test combination therapies, including PAP plus a pharmacological agent who have heart failure or are using opioid analgesics. We anticipate that findings will inform future clinical trials to improve care and quality of life among Veterans suffering from central sleep apnea, which remains difficult to treat using existing approaches.

PI_NAMEs: BADR, M.SAFWAN  (contact)

PROJECT_TERMS: Acetazolamide;adverse outcome;Agonist;Animals;Apnea;arm;Arousal;Breathing;Buspirone;Carbon Dioxide;Caring;Central Sleep Apnea;Chemoreceptors;Chronic;Clinical Trials;clinically relevant;Combined Modality Therapy;Complex;design;effective therapy;EFRAC;Ensure;Equilibrium;Event;experience;Experimental Designs;experimental study;Feedback;Future;Heart failure;heart failure with reduced ejection fraction;Heterogeneity;Human;Hyperpnea;hypnotic;Hypocapnia;Hypoxia;improved;indexing;innovation;Intervention;Laboratories;Literature;Motor output;novel;Opioid Analgesics;opioid use;optimal treatments;Outcome;Oxygen;Pathway interactions;Patient Care;Patients;Peripheral;pharmacologic;Physiological;Placebos;Plants;positive airway pressure;preconditioning;pressure;prevent;Quality of life;Randomized;receptor;receptor sensitivity;Recurrence;Resolution;Respiration;respiratory;response;Sensory;Series;Serotonin;Serotonin Agents;skills;Sleep;supplemental oxygen;targeted treatment;Testing;Therapeutic Intervention;Treatment Effectiveness;Veterans;Work;zolpidem

PROJECT_TITLE: Central Sleep Apnea: Physiologic Mechanisms to Inform Treatment