NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Services;Pediatric;Social Determinants of Health;Substance Misuse

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PSYCHIATRY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE Parental substance use (SU) is a leading cause of recent increases in CWS cases, and parental SU is associated with worse outcomes; however, engaging parents in SU services is challenging, as it requires collaboration across multiple systems (e.g., CWS, SU treatment agencies) and there are multiple points where parents can fall out of care. There is a critical need to better identify gaps in service provision in order to inform selection of appropriate EBPs that meet the needs of this population. The proposed project seeks to utilize community engagement and data-driven processes in EBP adoption and implementation in order to improve SU service provision for parents involved in CWS.

PI_NAMEs: DIR, ALLYSON LINDSAE (contact)

PROGRAM_OFFICER_NAME: HIGHSMITH, KEISHER S

PROJECT_TERMS: Address;Adoption;Area;Award;career;Caring;Child Abuse and Neglect;child services;Child Welfare;Collaborations;Communities;community based participatory research;community engaged approach;community engagement;community involvement;community partners;comorbidity;Complement;Complex;Data;Data Analyses;Decision Making;Dissemination and Implementation;Drops;effectiveness/implementation trial;Ensure;evidence base;Evidence based practice;Excision;experience;falls;Family;Fostering;Foundations;Goals;Health;HIV;Home;Human Resources;improved;improved outcome;Indiana;innovation;Interview;Maps;Mental Health;Mentors;Mentorship;Methods;Movement;Needs Assessment;Outcome;Parents;Pathway interactions;patient population;Patients;Population;preservation;Process;programs;Provider;Research;Research Activity;Research Ethics;Research Personnel;Resources;Rights;Role;service engagement;service gap;Service provision;Services;substance use;Substance Use Disorder;success;System;Training;United States National Institutes of Health;Vulnerable Populations

PROJECT_TITLE: The role of cross-system collaboration in implementation of evidence-based substance use practices in child welfare

STUDY_SECTION: SIHH

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


ADMINISTERING_IC: DA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Cocaine;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: This UG1 project will cohere local research strengths in brain imaging and clinical trials to establish a Clinical Laboratory with Integrated Neuroscience (CLIN) for Evaluation of Medications for Substance Use Disorders at the University of Pennsylvania. The initial demonstration project in the UG1 will test whether cariprazine, a candidate anti-relapse medication with high D3-affinity, demonstrates both target engagement (e.g., blunting of drug cue-triggered limbic activation) and preliminary clinical efficacy (reduced illicit drug use, and improved adherence to life-saving naltrexone) in patients with opioid use disorders.

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

PROGRAM_OFFICER_NAME: AKLIN, WILL

PROJECT_TERMS: Acceleration;addiction;Adherence;Adjuvant Analgesic;Affective;Affinity;Age;Agonist;Alcohols;American;Amygdaloid structure;antagonist;Attention;Automobile Driving;Baltimore;Behavioral;behavioral response;Brain;Brain imaging;Buprenorphine;Cannabidiol;Cannabis;Cause of Death;Clinical;clinical efficacy;Clinical Treatment;Clinical Trials;Cocaine;cocaine cue;cocaine use;Country;Cues;Data;Death Rate;Development;Dopamine;drug craving;Eligibility Determination;Evaluation;experience;Fentanyl;gamma-Aminobutyric Acid;Genetic Polymorphism;Globus Pallidus;Goals;Human;hypocretin;illicit drug use;Image;imaging probe;improved;Injectable;Injections;innovation;Inpatients;Knowledge;Laboratories;Life;Measures;Medial;medication compliance;medication-assisted treatment;Methadone;Motivation;Naltrexone;neuroimaging;Neurosciences;Nicotine;non-opioid analgesic;novel;Opioid;Opioid agonist;opioid epidemic;opioid mortality;opioid overdose;Opioid Receptor;opioid use;opioid use disorder;opioid withdrawal;Outcome;Outpatients;overdose death;Patients;patients who use opioids;Pennsylvania;Pharmaceutical Preparations;Philadelphia;Placebos;Positron-Emission Tomography;pre-clinical;prescription opioid;prevent;primary endpoint;Randomized;receptor;recruit;Relapse;Research;Research Personnel;Resources;response;Rewards;Risk Taking;secondary endpoint;Signal Transduction;Speed;Subgroup;Substance Use Disorder;synthetic opioid;Testing;tool;Tracer;treatment site;Universities;Urine;Ventral Striatum;Ventral Tegmental Area;Withdrawal Symptom;Work

PROJECT_TITLE: A Clinical Laboratory with Integrated Neuroscience (CLIN) for Early Evaluation of Medications for Substance Use Disorders


ADMINISTERING_IC: AI

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: ATLANTA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Pulmonary tuberculosis including drug-resistant disease is an enormous public health problem responsible for substantial morbidity and mortality worldwide with the number of deaths increasing for the first time in over two decades. This proposal seeks to better understand the host inflammatory response to Mycobacterium tuberculosis in individual human lung granulomas and to map the spatial distribution of newly implemented drugs used to treat drug-resistant disease within granuloma microenvironments. The long-term goals of this work are to provide data that will help guide the 1) development of host directed therapy to limit lung tissue damage and 2) design of optimal drug combinations to improve treatment and long-term outcomes among patients with pulmonary tuberculosis.

PI_NAMEs: KEMPKER, RUSSELL RYAN (contact);PRIDEAUX, BRENDAN

PROGRAM_OFFICER_NAME: LAUGHON, BARBARA E

PROJECT_TERMS: acquired drug resistance;Address;analytical method;Antibiotics;Area;Bacillus;bactericide;Biological Assay;Blood specimen;Catabolism;Cessation of life;Citric Acid Cycle;Clinical;Clinical Trials;Clinical Trials Design;cohort;Collaborations;Communicable Diseases;cooking;Country;Data;Data Analytics;data modeling;Data Set;design;Development;Disease;Disease Resistance;Dose;Drug Combinations;Drug Design;drug distribution;Drug Kinetics;Drug resistance;Drug resistance in tuberculosis;Drug resistant Mycobacteria Tuberculosis;Drug usage;Enrollment;Ensure;Environment;Excision;Genetic Transcription;global health;Goals;Granuloma;Heterogeneity;Human;Image;imaging modality;immunoregulation;improved;Individual;Inflammation;Inflammatory;Inflammatory Response;innovation;insight;Knowledge;Kynurenine;laser capture microdissection;Lesion;Linezolid;lipidomics;Lipids;liquid chromatography mass spectrometry;lung injury;lung lesion;Maps;mass spectrometric imaging;Metabolic;metabolomics;Methods;Modeling;Morbidity - disease rate;mortality;multidisciplinary;Multiomic Data;multiple omics;Mycobacterium tuberculosis;Necrosis;necrotic tissue;novel;Operative Surgical Procedures;Outcome;Pathologic;Pathway interactions;Patients;Pattern;Penetration;Pharmaceutical Preparations;pharmacokinetic model;Pharmacotherapy;Phenotype;Play;programs;Property;Public Health;pulmonary granuloma;Pulmonary Tuberculosis;Regimen;Research;Resected;Resistance;Resolution;response;Risk Reduction;Role;Signal Pathway;Signal Transduction;Site;Spatial Distribution;spatial integration;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Structure of parenchyma of lung;T cell response;targeted imaging;targeted treatment;Technology;Testing;Therapeutic;Time;Tissues;transcriptomics;Treatment Failure;treatment trial;Tryptophan;Tuberculosis;tuberculosis drugs;tuberculosis granuloma;tuberculosis treatment;United States National Institutes of Health;Variant;Visualization;Work

PROJECT_TITLE: Cavity and Granuloma Oriented Inflammation and Tissue Pharmacokinetics in Pulmonary Tuberculosis (COOK TB)

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Obesity;Prevention;Social Determinants of Health;Tobacco;Tobacco Smoke and Health

ORG_CITY: GALVESTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Since 2010, death rates from cardiovascular disease in the United States have failed to improve. Research has not identified why death rates from cardiovascular disease are stagnating and, for some age groups, increasing. Using novel statistical approaches, this research will provide key insights into this public health issue with the objective of informing policy.

PI_NAMEs: MEHTA, NEIL  (contact)

PROGRAM_OFFICER_NAME: KARRAKER, AMELIA WILKES

PROJECT_TERMS: Accounting;Acute;Address;Affect;age group;Alcohol consumption;American;analytical tool;Attention;Behavioral;Birth;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Cessation of life;Cholesterol;cigarette smoking;cohort;Complex;COVID-19 pandemic;Data;Death Rate;Dependence;Diabetes Mellitus;Disease;Disparity;Economics;Ethnic Origin;Event;experience;Failure;frailty;Future;geographic disparity;Geography;Growth;Health system;Heterogeneity;high risk;hypercholesterolemia;Hypertension;improved;Individual;insight;intergenerational;Joints;lens;Life;Life Expectancy;Measures;Methods;Modeling;mortality;Mortality Decline;Myocardial Infarction;novel;novel strategies;Obesity;older adult;overdose death;Paper;Pattern;Pharmaceutical Preparations;Policies;Population;population health;Population Heterogeneity;Prevalence;Process;Public Health;Publishing;Race;Recording of previous events;Research;Risk;Risk Factors;Role;Running;simulation;Smoking;social;Socioeconomic Status;socioeconomics;Stroke;Subgroup;Suicide;Survival Rate;Survivors;Time;trend;United States;United States National Academy of Sciences;Urbanicity;Work;young adult

PROJECT_TITLE: Identifying the Causes of the Stagnation in National U.S. Cardiovascular Disease Mortality

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


ADMINISTERING_IC: NS

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cerebrovascular;Nanotechnology;Neurosciences;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

ORG_STATE: CT

PHR: Narrative Neurodegenerative diseases and brain cancers are difficult to treat due to the presence of blood brain barrier (BBB), which prevents most of therapeutic drugs from penetrating the tight junctions of endothelial cells in the brain microvasculature and accessing the brain tissues. Ultrasound (US) has been shown to be the most effective and safe method to induce the BBB opening, facilitating the drug delivery into the brain tissue. Here, we propose a novel biodegradable US transducer based on biodegradable, flexible and highly piezoelectric nanofiber film of glycine crystals embedded inside a polycaprolactone (PCL) polymeric matrix to facilitate drug delivery through the BBB for the treatment of brain cancers

PI_NAMEs: NGUYEN, THANH  (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: absorption;Acoustics;Adjuvant;American;Amino Acids;Animal Model;Animals;Antineoplastic Agents;Blood;Blood - brain barrier anatomy;blood-brain barrier disruption;Body Weight;bone;Brain;Brain Neoplasms;brain surgery;brain tissue;Ceramics;cerebral microvasculature;Clinical;Clinical Treatment;Consumption;cranium;design;Devices;Diffusion;Disease;Drug Delivery Systems;Elements;Endothelial Cells;Excision;fabrication;Family suidae;Film;flexibility;Generations;Glycine;Histologic;Hour;Human;immunoreaction;Implant;implant material;implantation;In Vitro;in vivo;Lead;lead titanate zirconate;Lipids;Location;Magnetic Resonance Imaging;Malignant neoplasm of brain;manufacture;Methods;Monitor;mouse model;Mus;nanocomposite;nanofiber;nanopolymer;neural implant;Neurodegenerative Disorders;novel;Paclitaxel;Penetration;Performance;Pharmaceutical Preparations;polycaprolactone;Polymers;pre-clinical;pressure;prevent;Process;Property;Reporting;Research;Safety;safety assessment;Solvents;Sonication;Stainless Steel;success;systemic toxicity;Testing;Therapeutic;Thick;Thinness;Tight Junctions;Time;timeline;Trace metal;Transducers;Treatment Efficacy;tumor;tumor growth;Ultrasonic Therapy;Ultrasonic Transducer;ultrasound;voltage

PROJECT_TITLE: Novel Piezoelectric Amino-acid Ultrasound Transducer to Deliver Drugs Through the Blood Brain Barrier

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


NIH_SPENDING_CATS: Biotechnology;Genetics;HIV/AIDS;Immunization;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Humoral immunity requires the development of a diverse B cell repertoire tolerant of self. In this grant application, we will determine how the chemokine receptor CXCR4 directly instructs late B cell development and what this means for receptor editing which is a major mechanism of central tolerance.

PI_NAMEs: CLARK, MARCUS RAMSAY (contact);MANDAL, MALAY

PROGRAM_OFFICER_NAME: LEITNER, WOLFGANG W

PROJECT_TERMS: antagonist;Antigens;Applications Grants;autoreactivity;B cell repertoire;B-Cell Development;B-Lymphocytes;Biological;Biological Process;Bone Marrow;Cell Cycle;Cell Proliferation;Cells;central tolerance;chemokine;chemokine receptor;Complex;CXCR4 gene;CXCR4 Receptors;Data;Development;Ensure;Evaluation;experimental study;Failure;Genes;Genetic Recombination;Genomic Instability;human disease;Humoral Immunities;IGH@ gene cluster;IgK;IL7 gene;Immune response;Immunity;Immunoglobulin Gene Rearrangement;Immunoglobulin Genes;Immunoglobulin Light Chain Genes;Immunologics;Immunology;In Vitro;Infection;Interleukin 7 Receptor;IRF4 gene;leukemic transformation;Light;Light-Chain Immunoglobulins;Lymphopoiesis;Malignant Neoplasms;Mediating;Modeling;Molecular;novel;Peripheral;Play;Positioning Attribute;Process;progenitor;programs;Proliferating;receptor;Repression;Risk;Role;role model;Self Tolerance;Signal Pathway;Signal Transduction;Structure of germinal center of lymph node;surrogate light chain;System;TCF3 gene;Testing;Time;transmission process;Work

PROJECT_TITLE: Role of CXCR4 in immunoglobulin light chain recombination

STUDY_SECTION: CMIB

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


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences

ORG_CITY: SANTA CRUZ

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

ORG_STATE: CA

PHR: PROJECT NARRATIVE  Cognitive and affective processes engage distinct but interacting systems in the brain, which are important in decision-making but disrupted by stress. This proposal will use innovative approaches to identify the functional contributions of specific circuits and neuromodulation in frontal brain regions to cognitive-affective interactions during decision-making, and the effects of stress on these circuits. Elucidating these neural mechanisms will not only provide fundamental knowledge about the circuit mechanisms underlying higher brain functions, but also identify potential therapeutic targets for alleviating the detrimental effects of stress and psychiatric illnesses.

PI_NAMEs: WANG, KUAN HONG ;ZUO, YI  (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Affect;Affective;Anterior;Area;Attention;Brain;Brain imaging;Brain region;Calcium;Chromosome Mapping;Chronic stress;Cognitive;comparative;Complex;Data;Decision Making;Dendritic Spines;developmental genetics;Dopamine;dopaminergic neuron;Electrophysiology (science);Etiology;flexibility;frontal lobe;Goals;Human;Image;imaging study;Immediate-Early Genes;Impairment;in vivo;in vivo calcium imaging;in vivo imaging;innovation;Knowledge;Label;Lesion;Literature;Measures;Medial;Mental disorders;Midbrain structure;Modeling;Modernization;Monitor;Morphology;Motor;Mus;nerve supply;neural circuit;Neuroanatomy;neuromechanism;Neurons;neuroregulation;optogenetics;Outcome;Pathway interactions;Pattern;performance tests;Pharmacogenetics;pharmacologic;Predisposition;Prefrontal Cortex;Presynaptic Terminals;Process;Publishing;Risk Factors;sensor;Sensory;Societies;Stress;Structure;success;System;Techniques;Testing;therapeutic target;tool;two-photon;Ventral Tegmental Area;Viral

PROJECT_TITLE: Fronto-insular network in cognitive-affective interactions during decision-making


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: BOSTON

ORG_DEPT: DERMATOLOGY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PHR: Narrative. The main objective of this proposal is to understand the structure, function, and regulation of two biologically related enzymes, PTEN and USP7. Protein semi-synthesis strategies will be used to install site- specific and stoichiometric post-translational modifications (PTMs) and non-hydrolyzable mimics in order to evaluate the substrate selectivity of USP7 and how PTMs influence enzyme structure and function. Results from these studies can pave the way to new therapeutics to treat a variety of human disorders including cancer.

PI_NAMEs: DEMPSEY, DANIEL R. (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Acetylation;Active Sites;alpha helix;autism spectrum disorder;Automobile Driving;Binding;Biochemical;Biological;Biomolecular Nuclear Magnetic Resonance;C-terminal;career;Catalytic Domain;cell growth;Cell membrane;Cell Nucleus;Cell Proliferation;Cells;Chemicals;Ciona intestinalis;crosslink;Crystallography;Cytosol;Data;Deubiquitination;Disease;Double Minutes;Enzyme Inhibition;enzyme structure;Enzymes;Evaluation;Excision;experience;Genome Stability;Homologous Gene;Human;human disease;Hydrolase;improved;inorganic phosphate;insulin signaling;Label;Link;Lipids;Location;loss of function;Lysine;Malignant Neoplasms;Maps;Mediating;Membrane;Membrane Lipids;Methods;mimicry;Modification;Molecular;Molecular Conformation;Monoubiquitination;multicatalytic endopeptidase complex;Multiple Hamartoma Syndrome;Mus;Mutagenesis;Mutation;N-terminal;novel therapeutics;Nuclear;Pathologic;Pathway interactions;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Phospholipids;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;PI3K/AKT;Positioning Attribute;Post-Translational Protein Processing;Post-Translational Regulation;prevent;Process;Property;protein protein interaction;Proteins;Proto-Oncogene Proteins c-akt;Regulation;Reporting;Research;Resolution;Role;Second Messenger Systems;Series;Set protein;Signal Transduction;Site;skills;Structure;Surface;Tail;targeted treatment;Therapeutic Intervention;Titrations;TP53 gene;tripolyphosphate;tumor;Tumor Suppressor Proteins;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase;Ubiquitination;voltage

PROJECT_TITLE: Molecular Mechanisms of PTEN and USP7 Regulation

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Disorders;Cancer;Genetics;Lung;Lung Cancer;Neurosciences;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: PHARMACOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: The proposed studies seek to identify novel signaling networks that promote lung cancer brain metastasis, mediated in part by crosstalk of lung cancer metastases and neural cells in the brain microenvironment. Results from the proposed research will reveal novel biomarkers and identify druggable targets for the treatment of brain metastatic lung cancer and concomitantly reduce tumor-induced neurotoxicity.

PI_NAMEs: PENDERGAST, ANN MARIE  (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Address;Adenocarcinoma Cell;Animal Model;Astrocytes;biomarker identification;blood-brain barrier crossing;Brain;brain dysfunction;Brain Neoplasms;brain parenchyma;Cancer Etiology;Cancer Patient;cancer type;Cell Communication;cell type;Cells;Cessation of life;Clinical Trials;Data;Diagnosis;Differentiated Gene;Disease;Drug usage;druggable target;effective therapy;Exhibits;experience;experimental study;Genes;Genetic;Genetic Transcription;Growth;High Prevalence;Human;Impaired cognition;Impairment;Inflammatory Response;inhibitor;innovation;Knowledge;leukemia;Link;Lung Adenocarcinoma;lung cancer cell;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Metastatic malignant neoplasm to brain;Microglia;mimicry;Molecular;Morbidity - disease rate;mortality;mouse model;Neoplasm Metastasis;neoplastic cell;Nervous System;Neurodegenerative Disorders;Neuroepithelial, Perineurial, and Schwann Cell Neoplasm;Neurologic Symptoms;Neuronal Differentiation;Neurons;Neurosciences;neurotoxic;neurotoxicity;novel;novel marker;Pathogenesis;Pathway interactions;Patients;Phosphotransferases;pre-clinical;Process;Protein Tyrosine Kinase;Quality of life;Reporting;Research;Research Personnel;response;Role;Scientist;Seizures;Signal Transduction;single nucleus RNA-sequencing;Survival Rate;Technology;Testing;therapeutic target;Time;Transcript;Transcription Coactivator;transcription factor;transcriptomics;treatment response;Tropism;tumor;tumor microenvironment;tumor progression

PROJECT_TITLE: Targeting tumor-neural cell interactions to inhibit lung cancer brain metastasis

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Brain Disorders;Clinical Research;Dissemination and Implementation Research;HIV/AIDS;Mental Health;Neurosciences;Substance Misuse

ORG_CITY: MBARARA

ORG_COUNTRY: UGANDA

ORG_FIPS: UG

ORG_NAME: MBARARA UNIVERSITY/SCIENCE/ TECHNOLOGY

PHR: Narrative Non-Communicable Diseases are an emerging global pandemic with disproportionately higher rates in developing countries. Uganda with a large rural based population, requires development and implementation of evidence-based interventions to address real-life problems and provide sustainable solutions. The proposed Building capacity for Implementation Science research in Non-Communicable Diseases (BImS-NCDs)” training hub at MUST, will provide leadership, best practices, research support, mentoring and training in epidemiological, prevention, and implementation science approaches in NCDs across the lifespan to the partner institutions in rural Uganda.

PI_NAMEs: OBUA, CELESTINO  (contact);WAKIDA, EDITH

PROGRAM_OFFICER_NAME: LEVINTOVA, MARYA

PROJECT_TERMS: Address;Africa;Alcohol consumption;alcohol use disorder;Area;Behavioral;Brain;California;Cause of Death;Community of Practice;Developing Countries;Disease;Doctor of Philosophy;Epidemiology;Faculty;Funding;Future;General Hospitals;Grant;Health;Health Occupations;Health Professional;HIV;Human;implementation science;Infrastructure;Institution;Investments;Knowledge;Leadership;Life;life span;Massachusetts;Medicine;Mental disorders;Mental Health;Mentors;Mentorship;Methods;Mission;National Institute of Mental Health;National Institute of Neurological Disorders and Stroke;National Institute on Alcohol Abuse and Alcoholism;Nervous System;Nervous System Disorder;pandemic disease;Personal Satisfaction;Persons;Prevention;Public Health;Research;Research Support;Research Training;Rural;Science;skills;Technology;theories;tool;Training;Uganda;United States National Institutes of Health;Universities

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-L(55)R]


ORG_CITY: KAMPALA

ORG_NAME: MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES

PHR: Project narrative Despite the very high burden of rheumatic heart disease (RHD) in Uganda and most sub-Saharan African countries, there has been very little investment in research training and research. The proposed plan, the Impact Mentored Training Program, will train multidisciplinary health professionals at Makerere University College of Health Sciences to conduct RHD-related research with a special emphasis on clinical trials capacity building. Additionally, Impact will address the “double gender gap” in RHD research including (1) under-representation of women in research in Africa and (2) the dearth of sex- and gender-based analysis in RHD.

PI_NAMEs: BEATON, ANDREA ZAWACKI;OKELLO, EMMY ;SEWANKAMBO, NELSON K (contact)

PROJECT_TERMS: Address;Advisory Committees;Africa South of the Sahara;African;burden of illness;career development;Caring;Child;Clinical Trials;Collaborations;Country;Degree program;Disease;Doctor of Philosophy;E-learning;Early Diagnosis;Educational workshop;Ensure;experience;Fellowship;Funding;Gender;Generations;Goals;Grant;Guidelines;Health;Heart;heart disease prevention;Hospitals;improved;Income;innovation;Institution;Knowledge;life span;low and middle-income countries;Medical center;medical schools;Medicine;Mentors;next generation;parity;Pediatric Hospitals;Persons;Policies;professor;programs;recruit;Research;Research Activity;Research Personnel;Research Training;Resources;Rheumatic Heart Disease;sex;success;Training;Training Activity;Training Programs;Training Support;Translating;Uganda;United States National Institutes of Health;Universities;Vision;webinar;Woman

PROJECT_TITLE: Reducing the Impact of Rheumatic Heart Disease across the Life Span: The Impact Program


NIH_SPENDING_CATS: Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Neurosciences;Pediatric

ORG_CITY: TUCSON

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: NARRATIVE This renewal proposal will continue to develop and expand a model program to recruit, train, and sustain a growing cadre of diverse/disadvantaged (including under-represented minority) high school students and progressing undergraduates in biomedical research broadly targeting neurosciences, neurological disorders, and stroke. Using our inquiry-driven curriculum, we will energize a diverse career pipeline to promote networking, retention, and career progression, thereby contributing to NIH's strategic plan of creating the diverse research teams of the future and NINDS's mission of advancing translation of medical discoveries in the neurosciences from bench to bedside to community.

PI_NAMEs: PORRECA, FRANK ;WITTE, MARLYS HEARST (contact);WITTE, RUSSELL S

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: addiction;aluminum sulfate;Alzheimer's Disease;Arizona;Basic Science;bench to bedside;Biomedical Research;Blood - brain barrier anatomy;Body System;Brain;brain abnormalities;Brain Neoplasms;career;Cellular Phone;Cerebrum;Clinical;Clinical Research;Cognition;Collaborations;Communications Media;Communities;community engagement;Complex;Computer software;Creativeness;Curiosities;Databases;Deep Brain Stimulation;design;Disadvantaged;Disease;Educational Curriculum;Educational process of instructing;Epilepsy;Equilibrium;Evaluation;Exhibits;experience;Faculty;Feedback;Fright;Funding;Future;Goals;Habits;Headache;Health;health disparity;health literacy;high school;High School Student;Hybrids;Hydrocephalus;improved;in silico;In Situ;In Vitro;in vivo;Individual;Infrastructure;innovation;Institution;Interdisciplinary Study;interest;International;Knowledge;Laboratories;Language;Leadership;Life;Link;literacy;Longterm Follow-up;Lymphovascular;Medical;medical specialties;Medical Students;Medicine;Mentors;Mind;Mission;Modeling;Molecular;Monitor;multidisciplinary;Multimedia;Muscular Dystrophies;National Institute of Neurological Disorders and Stroke;Nervous System;Nervous System Disorder;Neuroanatomy;Neurobiology;neurogenomics;neuroimaging;neuroprotection;Neurosciences;novel;Organ;Pain;Parkinson Disease;peer;peer networks;peer support;Periodicals;Peripheral Nervous System;Pharmacology;Physiology;Population Research;Productivity;programs;Proteomics;Psychiatry;Reaction;recruit;Registries;Research;Research Personnel;retention rate;role model;Science;skills;Sleep disturbances;Social Network;Specialized Center;Spinal Cord;Strategic Planning;Stroke;student participation;Students;summer institute;summer research;summer student;support network;Surveys;Talents;Training;Training Programs;Translating;Translation Process;Translational Research;Translations;Traumatic Brain Injury;undergraduate student;Underrepresented Minority;United States National Institutes of Health;Universities;virtual;Vocabulary

PROJECT_TITLE: High School Student NeuroResearch Program (HSNRP)


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Clinical Research;Immunotherapy;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on identifying the alterations in the im- mune system that impact amyotrophic lateral sclerosis (ALS) and also focuses on identifying whether these altered immune profiles are influenced by sex- and age-specific factors. The development of such strategies will greatly advance the ability to develop personalized treatment approaches for persons with ALS based on immunomodulatory drugs. Thus, the proposed research is relevant to part of the NIH’s mission that pertains to developing the fundamental knowledge about the nervous system and using that knowledge to reduce the bur- den of neurological disease.

PI_NAMEs: GOUTMAN, STEPHEN  (contact);MURDOCK, BENJAMIN JOSEPH

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Address;Affect;Age;age related;ALS patients;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;Animals;Area;biobank;Biological Markers;Blood;Blood specimen;CD4 Positive T Lymphocytes;Cell Count;Cells;Cessation of life;Characteristics;Clinical;Clinical Trials;Coculture Techniques;cohort;cytotoxicity;Data;Data Set;deep neural network;design;Development;Disease;Disease Progression;drug development;drug repurposing;effective therapy;Estrogens;Foundations;Goals;Gonadal Steroid Hormones;Hormones;Human;Immune;immune function;immune modulating agents;Immune response;Immune system;Immune Targeting;Immunophenotyping;In Vitro;in vivo;Individual;Induced pluripotent stem cell derived neurons;Inflammation;Inflammatory;innovation;insight;interest;Knowledge;knowledge base;Link;Literature;Longitudinal cohort;Longitudinal Studies;Mediating;Michigan;Mission;Motor Neuron Disease;Natural Killer Cells;Nervous System;Nervous System Disorder;neuroinflammation;Neurons;neurotoxicity;neutrophil;new therapeutic target;Outcome;Pathway interactions;Patients;Peripheral;peripheral blood;personalized medicine;personalized therapeutic;Persons;Phenotype;Population;Positron-Emission Tomography;predictive modeling;Public Health;Recording of previous events;Research;Sampling;Severity of illness;sex;sex variable;Survival Rate;Testosterone;Therapeutic;therapeutic development;therapeutic target;Time;Toxic effect;transcriptome sequencing;United States National Institutes of Health;Universities

PROJECT_TITLE: Creating a foundation for personalized age- and sex-based immune-targeted therapies from an ALS longitudinal cohort by identifying peripheral and central immune signatures

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: DAVIS

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The proposed research focuses on understanding how plants regulate the strength, duration and specificity of immune responses. Due to significant similarity in immune perception between plants and vertebrates, we anticipate experimental insights will broadly enhance our understanding of immune perception and signaling.

PI_NAMEs: COAKER, GITTA LAUREL (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Animals;Binding;Cells;Cysteine;Data;defense response;Exhibits;Germ Lines;Immune;Immune response;Immune signaling;Immunologic Receptors;Innate Immune Response;Innate Immune System;insight;Leucine-Rich Repeat;Mediating;next generation;Nucleotides;Organ;pathogen;pathogenic bacteria;Pattern recognition receptor;Perception;Phosphotransferases;Plant Leaves;Plants;Post-Translational Protein Processing;Protein Kinase;receptor;Regulation;Research;response;Role;Scientist;Signal Transduction;Specificity;Surface;Training;Vertebrates

PROJECT_TITLE: Immune perception of bacterial pathogens in plants

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


NIH_SPENDING_CATS: Brain Disorders;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: CINCINNATI

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: PROJECT NARRATIVE Cortical spreading depolarizations (CSDs), or “brain tsunamis” are waves of electrical activity that occur in 60% of patients with traumatic brain injury (TBI) and are associated with poor outcomes. In this proposal we test the hypothesis that CSDs have remote effects on hippocampus after TBI. Successful completion of this project will help determine how CSDs cause poor outcomes, and hence can identify treatment targets.

PI_NAMEs: NGWENYA, LAURA BENJAMIN (contact)

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: Adult;adult neurogenesis;Animals;Area;Brain;Brain Injuries;Brain region;Caring;Cessation of life;Chemicals;Clinical;Clinical Research;Data;designer receptors exclusively activated by designer drugs;Development;Electrophysiology (science);entorhinal cortex;experience;Experimental Models;experimental study;fluid percussion injury;Generations;Genetic;Gliosis;Goals;granule cell;Hippocampus;Histopathology;Hospitalization;Human;improved outcome;injured;Injury;injury-related death;insight;Interphase Cell;Intervention;Knowledge;Lateral;Learning;Mediator;Memory;Modeling;Morphology;neural circuit;neuron loss;Neurons;optogenetics;Outcome;Pathologic;Pathology;Patients;Pattern;prevent;Process;Proliferating;Property;Rattus;remote assessment;Seizures;Survivors;Synapses;TBI Patients;Testing;Therapeutic;therapy development;Tissues;Traumatic Brain Injury;United States

PROJECT_TITLE: Defining the remote effects of cortical spreading depolarizations on hippocampus after traumatic brain injury

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


NIH_SPENDING_CATS: Prevention

ORG_CITY: WASHINGTON

ORG_DEPT: MISCELLANEOUS

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative The proposed United States-Zambia Addressing Risk Factors for Non-Communicable Diseases in Zambia (US-Zambia Risk-NCD) program will enhance capacity for research, training and policy direction on the long-term health and economic consequences of major risk factors for NCDs, which are large contributors to Zambia’s burden of disease. Applying transformative capacity development model for Zambians by Zambians with US technical assistance, we will address the major gap in chronic disorders by focusing on key risk factors and establish mechanisms to ensure long-term sustainability for a strong research enterprise in Zambia. The program aims to develop trainee researcher skills; create a sustainable platform for discussion among researchers, practitioners, policy makers and donors; and further strengthen the research enterprise around NCDs at UNZA by establishing a unit to support such research.

PI_NAMEs: HYDER, ADNAN A (contact);PAICHADZE, NINO ;ZYAMBO, COSMAS

PROJECT_TERMS: Address;Africa;burden of illness;Cessation of life;Chronic;Collaborations;Consumption;Data;Databases;Dedications;Development;disability;Disease;disorder risk;Economics;Educational workshop;Evaluation;Faculty;Gender;Goals;Health;Home;Human Resources;implementation research;Individual;innovation;Institution;Intervention;life span;Master of Public Health;Measures;Medicine;Modeling;online course;Persons;Policies;premature;programs;Public Health Schools;Research;Research Personnel;Risk;Risk Factors;symposium;Training;Training Programs;United States;Universities;Washington;webinar;Work;Zambia

PROJECT_TITLE: United States-Zambia Addressing Risk Factors for Non-Communicable Diseases (US-Zambia Risk NCD)


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: IRVINE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: RELEVANCE Genetically programmed degeneration of photoreceptor cells and the retinal pigment epithelium is the underlying cause of blindness in nearly all inherited retinal diseases, many of which have no or only minimally effective treatment options. Thus, additional therapeutic approaches are urgently needed to diminish vision loss associated with these disorders. Using novel genome- editing therapeutic interventions, we aim to slow or halt the development and progression of retinopathies in animal models as a prelude to clinical evaluation of these therapies in humans.

PI_NAMEs: PALCZEWSKI, KRZYSZTOF  (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: 220kDa rod outer segment rim protein;Address;Adenine;Alleles;amino group;Animal Model;autosome;base;base editing;base editor;Benchmarking;Biological Assay;Blindness;Cell Line;Cell Physiology;cell type;Cells;Charge;clinical translation;Color;Complex;Coomassie blue;COVID-19 vaccine;CRISPR/Cas technology;Data;Deletion Mutation;delivery vehicle;Derivation procedure;Development;Disease;disease-causing mutation;DNA;DNA Double Strand Break;DNA Integration;effective therapy;Engineering;Enzymes;experimental study;Eye;FDA approved;functional restoration;gene augmentation therapy;gene function;gene therapy;Genes;Genetic;Genome;genome editing;genome editor;Genomic DNA;Genomics;Guide RNA;Hereditary Disease;Histology;Human;human disease;human model;Imaging Techniques;immunoregulation;improved;in vivo;Inherited;innovation;Insertion Mutation;insertion/deletion mutation;interest;Label;Laboratories;Leber's amaurosis;Link;lipid nanoparticle;Lipids;Mass Spectrum Analysis;Membrane;Messenger RNA;Methods;Modeling;mouse model;Multienzyme Complexes;Mus;mutant;Mutate;Mutation;mutation correction;next generation sequencing;novel;Nucleosides;particle;Penetration;Peptides;photoreceptor degeneration;Photoreceptors;Phototransduction;Point Mutation;preclinical study;Preclinical Testing;prime editing;prime editor;Protein Analysis;Protein Binding Domain;protein expression;Proteins;Publications;Publishing;Quality of life;Reagent;repaired;Reporter;research clinical testing;response;Retina;Retinal Degeneration;Retinal Diseases;Retinitis Pigmentosa;retinol isomerase;Rhodopsin;Ribonucleoproteins;risk minimization;RNA;RNA delivery;RNA Stability;RNA vaccine;Route;RPE65 protein;Safety;screening;Stargardt's disease;Structure of retinal pigment epithelium;success;System;Technology;Testing;Therapeutic;therapeutic genome editing;Therapeutic Intervention;Therapy Evaluation;tool;Toxic effect;transcriptome;transversion mutation;two photon microscopy;two-photon;Viral;Visual Cortex;visual cycle;Visual impairment;Western Blotting

PROJECT_TITLE: Precision genome editing in vivo to treat retinal diseases

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Sleep Research

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The circadian clock controls 24-hour rhythms in the body, and is an important regulator of brain function. We hypothesize that disturbances in circadian function, which are common in our modern society, can promote neurodegenerative diseases, in particular Alzheimer’s Disease. We will investigate the functions of a certain set of “clock proteins”, termed REV-ERBs, which control circadian rhythms in the brain, and determine molecular mechanisms by which they may influence neuroinflammation in Alzheimer’s Disease. We hope to use novel therapies to directly activate or block the function of these REV-ERB proteins to prevent Alzheimer’s Disease and other neurodegenerative diseases.

PI_NAMEs: MUSIEK, ERIK STEVEN (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: Acceleration;age related neurodegeneration;Agonist;Alzheimer associated neurodegeneration;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid beta-Protein;amyloid pathology;Amyloidosis;antagonist;APP-PS1;ARNTL gene;Brain;C3 gene;Cell Physiology;cell type;Cells;circadian;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Clock protein;common symptom;Complement;Complement 4b;complement C3 precursor;Data;derepression;Diurnal Rhythm;gene complementation;Gene Expression;gene repression;Genes;Genetic;Genetic Transcription;glial activation;Gliosis;Goals;Hippocampus;Homologous Gene;Hour;in vivo;Inflammation;Innate Immune System;Knockout Mice;Link;Mediating;Metabolic;Metabolism;Methods;Microglia;Modernization;Molecular;mouse model;Mus;Nerve Degeneration;Neurites;Neurodegenerative Disorders;neuroinflammation;neuroprotection;novel;novel strategies;novel therapeutics;Nuclear Receptors;Organ;overexpression;oxidative damage;Pathogenesis;Pathway interactions;Periodicity;Peripheral;Phagocytes;Phagocytosis;Pharmaceutical Preparations;pharmacologic;Play;prevent;Process;Proteins;Publishing;Regulation;Role;Senile Plaques;Signal Transduction;small molecule;Societies;Synapses;synaptic pruning;therapeutic target;Transcriptional Regulation;transcriptome sequencing;Transgenic Mice;Up-Regulation;Viral Vector

PROJECT_TITLE: Role of REV-ERB Proteins in Neuroinflammation and Alzheimer's Disease

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: PULLMAN

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: WASHINGTON STATE UNIVERSITY

ORG_STATE: WA

PHR: A limiting factor in understanding gene regulation is insufficient knowledge of how regulatory information is encoded in the genome. By studying regulatory elements functionally defined by transcription across evolution, this proposal aims to reveal the key DNA motifs, transcription factors and regulatory networks mediating eukaryotic gene expression. These insights should also be instrumental to better interpret the human genome.

PI_NAMEs: DUTTKE, SASCHA H. (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Award;Binding Sites;Bioinformatics;Biological Process;Biology;Biotechnology;Cell Cycle Regulation;Code;Collaborations;Communities;comparative;comparative genomics;Computer software;Conserved Sequence;Data;data access;Data Analyses;data portal;Data Set;Distant;DNA;Documentation;Enhancers;Eukaryota;Evolution;Fruit;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;Genetic Variation;Genome;genome-wide;Health;Human;Human Genome;insight;Introns;Knowledge;Life;Maps;Mediating;Mentors;Methods;Mus;next generation sequence data;novel;novel strategies;Nucleic Acid Regulatory Sequences;Organism;Orthologous Gene;Pathway interactions;Phase;Positioning Attribute;Preparation;programs;promoter;Proteins;Publishing;recruit;Regulation;Regulatory Element;Research;RNA;Sequence Analysis;Site;skills;Small RNA;software development;TATA Box;Testing;tool;training opportunity;Transcript;transcription factor;Transcription Initiation;Transcription Initiation Site;transcription regulatory network;transcriptome;transcriptome sequencing;Translations;Trees;Untranslated RNA;Update;Variant;Vertebrates;virtual;Visualization;Well in self;Work;Writing

PROJECT_TITLE: Exploiting Natural Genetic and Organismic Variation to Identify the DNA Motifs Regulating Transcription


NIH_SPENDING_CATS: Behavioral and Social Science;Building Research Capacity at Institutions with Limited NIH Funding;Neurosciences;Sleep Research

ORG_CITY: Boulder

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Public Health Relevance Sleep and circadian rhythms are fundamental regulators of neurological function and their dysregulation cause, promote, and exacerbate neurological disorders. This educational program will increase the number of undergraduate students from underrepresented populations in the U.S. Biomedical Sciences for advanced academic training and foster their pursuing sleep and circadian science careers to promote a diverse workforce.

PI_NAMEs: WRIGHT, KENNETH P (contact)

PROJECT_TERMS: Academic Training;Address;Admission activity;African American population;Alaska Native;American Indians;Area;Biological Process;Biomedical Research;Black American;career;Career Choice;circadian;Circadian Rhythms;Clinical;cohort;Colorado;Communities;Competence;design;Development;Development Plans;disability;disadvantaged background;Diverse Workforce;diversity and equity;diversity and inclusion;Doctor of Philosophy;Education;Education Projects;Educational Curriculum;Educational process of instructing;Ensure;ethnic minority;Evaluation;experience;Exposure to;Faculty;faculty mentor;First Generation College Students;Fostering;Foundations;Funding;Goals;Hispanic Populations;Housing;Impairment;Individual;innovation;Institution;Knowledge;laboratory experience;Latino Population;Leadership;lectures;Life;Manuscripts;medical schools;Mentors;Michigan;Mission;Monitor;Morehouse School of Medicine;National Institute of Neurological Disorders and Stroke;Native Hawaiian or Other Pacific Islander;Nervous System Disorder;Nervous System Physiology;Neurosciences;next generation;organizational climate;Outcome;peer coaching;Pennsylvania;Positioning Attribute;programs;Psyche structure;public health relevance;Qualifying;racial minority;recruit;Research;Research Activity;Research Personnel;Resources;rural area;Schools;Science;Scientist;Site;Sleep;sound;Students;success;summer program;summer research;symposium;Talents;Texas;Text;Training;training opportunity;Training Programs;undergraduate research experience;undergraduate student;Underrepresented Populations;United States;Universities;virtual;Vocational Guidance;Wages;Washington;web page;Woman

PROJECT_TITLE: Multi-Institutional Summer Undergraduate Research Program to Promote Diversity and Excellence in Sleep and Circadian Research Careers


NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Immunotherapy;Prostate Cancer;Radiation Oncology;Urologic Diseases

ORG_CITY: NEW YORK

ORG_DEPT: UROLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Narrative Metastatic castration-resistant prostate cancer remains an incurable disease. Alterations in the genes that regulate the body’s processes for repairing damaged DNA, particularly BRCA2, have been linked to treatment failure and poor prognosis for men with prostate cancer. In this project, we aim to comprehensively investigate the role of such alterations in the development of lethal, untreatable prostate cancer with the goal of identifying and developing novel combination treatments, such as targeted immunotherapy and radiotherapy.

PI_NAMEs: CHAKRABORTY, GOUTAM  (contact);PILLARSETTY, NAGAVARAKISHORE ;PONOMAREV, VLADIMIR

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Address;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Antigen Targeting;Biometry;BRCA2 gene;BRCA2 Mutation;Cancer Biology;Cancer Etiology;Cancer Patient;CAR T cell therapy;Caring;Castrate sensitive prostate cancer;Castration;Cells;Cellular biology;Cessation of life;chimeric antigen receptor T cells;Clinical;Clinical Oncology;Clinical Trials;Clinical Trials Design;cohort;Combined Modality Therapy;CRISPR screen;CRISPR-mediated transcriptional activation;Data;Development;Discipline;Disease;DNA Double Strand Break;DNA Repair;DNA Sequence Alteration;effective therapy;efficacy study;Epidemiology;Exhibits;FOLH1 gene;Foundations;gain of function;Gene Mutation;gene repair;Genes;Genomic Instability;Goals;Heterozygote;immunogenic;Immunology;Immunotherapy;in vivo;Indolent;Induced Mutation;insight;Knock-out;Lesion;Link;loss of function;Malignant neoplasm of prostate;men;Molecular;mortality;Mutation;novel;Organoids;PARP inhibition;Pathology;Patients;pharmacologic;Poly(ADP-ribose) Polymerase Inhibitor;pre-clinical;Pre-Clinical Model;Process;Prognosis;programs;prospective;prostate cancer cell;prostate cancer cell line;prostate cancer progression;Prostate Cancer therapy;Radiation therapy;Radiochemistry;rational design;receptor function;Reporting;Research Personnel;Resistance;response;Role;Signal Pathway;synergism;Targeted Radiotherapy;targeted treatment;Testing;Therapeutic;therapeutic development;therapy resistant;Time;Transcriptional Regulation;Treatment Failure;treatment strategy;tumor;Up-Regulation;Work

PROJECT_TITLE: Functional Characterization and Development of Therapeutic Paradigms for DNA Damage Repair (DDR)-deficient Lethal Prostate Cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Prevention;Vaccine Related

ORG_CITY: GALVESTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

PHR: PROJECT NARRATIVE: The current Coronavirus disease 2019 virus (COVID-19) pandemic has made a serious impact on global public health and economy. The goal of this project is to develop COVID-19 subunit vaccine formulated by a modified porous silicon microparticle and delivered by parenteral and mucosal prime/boost vaccination. This vaccine approach is expected to generate both systemic and mucosal humoral and Th-1 directed cellular immune responses, which will provide long-lasting cross protection against SARS-CoV-2 variants of concern and prevention of future coronavirus outbreaks.

PI_NAMEs: WANG, TIAN  (contact)

PROGRAM_OFFICER_NAME: GORDON, JENNIFER L

PROJECT_TERMS: 2019-nCoV;Adjuvant;airway epithelium;Antigens;B-Lymphocytes;betacoronavirus;cell mediated immune response;Cells;Clinical;Clinical Trials;combat;combinatorial;Coronavirus;COVID-19;COVID-19 vaccine;cross immunity;cross reactivity;Disease;Disease Outbreaks;dosage;Dose;efficacy evaluation;Epithelial Cells;Epithelium;Epitopes;Exhibits;FDA Emergency Use Authorization;FOLH1 gene;Formulation;Future;future outbreak;Goals;Grant;Hamsters;Helper-Inducer T-Lymphocyte;Human;Immune;Immune response;Immunity;Immunization;immunogenicity;Immunoglobulin A;in vivo;Infection;Infection Control;Inflammation;Lung;Measures;Mediating;Mesocricetus auratus;Messenger RNA;Modeling;Mucosal Immune Responses;Mucosal Immunity;mucosal uptake;mucosal vaccination;Mucous Membrane;Mus;Nasal Epithelium;Nose;novel vaccines;Nucleocapsid;old mice;pandemic virus;parenteral administration;particle;Population;Porosity;prevent;Prevention;protective efficacy;Proteins;Public Health;receptor binding;Reporting;response;RNA vaccine;Role;Route;safety testing;Sarbecovirus;SARS-CoV-2 B.1.1.529;SARS-CoV-2 B.1.617.2;SARS-CoV-2 infection;SARS-CoV-2 transmission;SARS-CoV-2 variant;Severe Acute Respiratory Syndrome;Severity of illness;Silicon;Subunit Vaccines;success;T-Lymphocyte;T-Lymphocyte Epitopes;Testing;Toxic effect;transmission process;uptake;Vaccination;Vaccine Antigen;vaccine candidate;vaccine development;vaccine platform;vaccine-induced immunity;Vaccines;Variant;variants of concern;Viral Load result;viral transmission;Virus Diseases;Work

PROJECT_TITLE: Porous silicon microparticle-based subunit vaccines for SARS-CoV-2

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Pediatric;Rare Diseases;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Shigella is a primary cause of moderate-to-severe diarrhea including dysentery in children living in impoverished areas of the world. The current World Health Organization (WHO) guidelines for treatment of shigellosis (in the absence of a rapid, simple and inexpensive diagnostic test) recommends treatment with antibiotics when presence of visible blood in stool, although, majority of the Shigella diarrhea are watery diarrhea in nature and thus the non-dysentery Shigella associated diarrhea (NDSD) cases would not be treated, which might result in an appreciable amount of unaddressed Shigella-associated morbidity and mortality. We aim to study the pathophysiology of NDSD and the impact of NDSD in children to understand if there is a need to change the current treatment guidelines for shigellosis to improve survival and long-term developmental potential in children and we also aim to evaluate our novel, simple, rapid and sensitive diagnostic assay, if capable of identifying the patients with shigellosis who will benefit from antibiotics.

PI_NAMEs: CHAKRABORTY, SUBHRA  (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Address;Age;Anthropometry;Antibiotic Therapy;Antibiotics;Bangladesh;Biological Assay;Birth;Blood;Blood specimen;care seeking;Case/Control Studies;Child;Child Development;Child Health;Chronic;Clinical;Cognitive;cognitive development;Cohort Studies;Collaborations;cost;Country;Detection;Development;diagnostic algorithm;diagnostic assay;Diagnostic tests;Diarrhea;Dysentery;Enrollment;evidence base;Feces;field study;fitness;Functional disorder;Future;Gene Expression Profile;Guidelines;gut health;gut inflammation;Home visitation;Hospitalization;Hospitals;Hydration status;Impairment;improved;indexing;India;Infection;Inflammation;Inflammatory;intestinal epithelium;Invaded;Kinetics;Laboratories;Length;Life;Literature;Malnutrition;Morbidity - disease rate;mortality;mortality risk;Mucous Membrane;Nature;novel;nutrition;Nutritional status;Patients;Performance;Peru;Poverty Areas;prospective;Proxy;Publishing;rapid test;Recommendation;recruit;Research;Risk;Rural;Rural Hospitals;rural setting;Sampling;Shigella;Shigella Infections;standard care;stool sample;Symptoms;systemic inflammatory response;Testing;treatment guidelines;World Health Organization;Zambia

PROJECT_TITLE: The impact of non-dysentery Shigella-associated diarrhea in children

STUDY_SECTION: CRFS

STUDY_SECTION_NAME: Clinical Research and Field Studies of Infectious Diseases Study Section[CRFS]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative This project is relevant to public health because it will investigate the function of a human enzyme involved in the metabolism of fats. Specifically, the project will elucidate how this enzyme modifies the chemical composition of membranes and how these modifications impact the metabolism of lipoproteins and the regulation of body fat. As a result, the work will provide fundamental knowledge relevant to obesity, the metabolic syndrome, and atherosclerosis.

PI_NAMEs: HUSSAIN, M MAHMOOD;SCHLAME, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Ablation;Acyl Coenzyme A;Acylation;Acyltransferase;Address;Affect;Atherosclerosis;Biochemical Pathway;Biochemical Reaction;Biological Process;Body fat;Carbon;Chemicals;Collaborations;Data;deacylation;Disease;Enzymes;experience;Fatty Acids;Glycerol;Health;Hepatic;Hepatocyte;Human;In Vitro;Isotope Labeling;knock-down;Knock-out;Knowledge;Laboratories;Lecithin;Link;lipid biosynthesis;lipid metabolism;lipidome;lipidomics;Lipids;Lipoproteins;Low Density Lipoprotein Receptor;Mass Spectrum Analysis;Measures;Membrane;Metabolic syndrome;Metabolism;Methods;Methylation;Modeling;Modification;Mus;novel;Obesity;Organelles;Palmitates;Pathway interactions;Phosphatidylethanolamine;Phospholipase A2;Phospholipids;Play;Positioning Attribute;Production;Public Health;reconstitution;Regulation;Resolution;Role;Saturated Fatty Acids;Second Messenger Systems;Specificity;Stearates;stearoyl-coenzyme A;Testing;Time;Tissues;tool;Unsaturated Fatty Acids;Vertebral column;Work

PROJECT_TITLE: The Function of Mammalian LPGAT1

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Pancreatic Cancer;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Public Health Relevance (Project Narrative) International consensus guidelines have a dismal specificity for discriminating benign from malignant intraductal papillary mucinous neoplasm (IPMN) (a type of common pancreatic cyst and precursor to pancreatic cancer) and a poor accuracy of predicting IPMN malignant progression during surveillance. The proposed study is expected to develop models that integrate plasma and pancreatic cyst fluid levels and trajectories of protein and metabolites with clinical and imaging features, which are more accurately predictive of IPMN malignant progression and early-stage pancreatic cancer than the current clinical guidelines based solely on clinical and imaging findings. Such expected results are significant because they will lead to an improved clinical management of IPMN and an increased long-term survival of pancreatic cancer patients.

PI_NAMEs: SCHMIDT, CHRISTIAN MAXIMILLIAN (contact);ZHANG, JIANJUN

PROGRAM_OFFICER_NAME: ZHU, CLAIRE

PROJECT_TERMS: Age;Benign;Biological;Biological Markers;biomarker identification;CA-19-9 Antigen;Cancer Center;cancer invasiveness;Clinical;Clinical Management;Clinical/Radiologic;cohort;Colorectal;Consensus;cost;Cyst;Cyst Fluid;Data;density;Diagnosis;Diagnostic;Dinoprostone;Disease;Dysplasia;Early Diagnosis;Early identification;Enrollment;Enzyme-Linked Immunosorbent Assay;Excision;follow-up;Guidelines;high risk;Image;improved;Incidence;Indiana;International;Lung;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Measures;metabolomics;Modeling;mortality;Mucinous Neoplasm;Natural History;neoplasm surgery;Nested Case-Control Study;Operative Surgical Procedures;Ovarian;pancreatic cancer patients;Pancreatic Cyst;Pancreatic Ductal Adenocarcinoma;Papillary;Pathology;Patients;Physicians;Pilot Projects;Plasma;Population;predictive marker;predictive signature;Prognosis;progression risk;prospective;Prospective, cohort study;Prostate;Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial;Proteins;Proteomics;PTPRJ gene;public health relevance;Race;radiological imaging;Recommendation;Resected;Risk;risk prediction model;Sampling;sex;Specificity;Surgical Pathology;surveillance study;Testing;THBS2 gene;TIMP1 gene;tumor progression;Universities;Unnecessary Surgery;Utah

PROJECT_TITLE: Longitudinal Proteomic and Metabolomic Predictors of Pancreatic Cyst Malignant Progression and Early Stage Pancreatic Cancer


ORG_CITY: MINNEAPOLIS

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Viral vectors are an essential component in many disease therapies but they have practical limitations that warrant investments in rational engineering to enable precision gene therapy. We develop a novel viral vector platform technology that uses antibodies to target gene delivery to specific cell types.

PI_NAMEs: LEBEAU, AARON MATTHEW;SCHMIDT, DANIEL  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Address;Adverse reactions;Affinity Chromatography;Animals;Antibodies;Binding;Biochemical;Biomanufacturing;Biophysical Process;Capsid;Capsid Proteins;Cell Surface Receptors;cell type;Cells;Clinic;Clinical Trials;Coupled;Dependovirus;design;Development;Disease;Dose;Ectopic Expression;Engineering;Enhancers;Gene Delivery;gene therapy;Generations;Genes;Genetic Engineering;Hereditary Disease;Human;immunodeficiency;improved;in vivo;Infection;Insertional Mutagenesis;Investments;Lead;Libraries;Machine Learning;Malignant neoplasm of prostate;Malignant Neoplasms;Maps;Mediating;Molecular;Monoclonal Antibodies;Mus;neutralizing antibody;novel;novel therapeutic intervention;Nucleic Acid Regulatory Sequences;Outcome;patient safety;Patients;Performance;Population;Positioning Attribute;Production;promoter;Property;prototype;Randomized;receptor;Reporting;Risk;Safety;scaffold;Serotyping;Site;Specificity;Structure;Surface;Technology;technology platform;technology validation;therapeutically effective;tissue tropism;Tissues;Transgenes;Tropism;Variant;Viral;viral gene delivery;Viral Vector;Virion;Virus;virus tropism;wasting;Work;Xenograft Model

PROJECT_TITLE: Viral vector technology for cell type specific gene delivery

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes;Digestive Diseases;Estrogen;Women's Health Research

ORG_CITY: TUSKEGEE INSTITUTE

ORG_DEPT: BIOLOGY

ORG_NAME: TUSKEGEE UNIVERSITY

ORG_STATE: AL

PHR: Project narrative: Diabetes-associated gastrointestinal motility disorders are a major public health concern and are more prominent in females than males. The long-term goal of this project is to understand the mechanisms of sexual dimorphism in gastrointestinal motility and how diabetes causes motility disorders in females. The studies may offer insights into the development of new therapeutics for diabetes-associated motility disorders.

PI_NAMEs: MAHAVADI, SUNILA  (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Acetylation;Agonist;Animal Model;Autonomic nervous system;Binding;chromatin immunoprecipitation;clinically significant;Colon;Constipation;Coupled;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cyclic GMP;Data;Development;Diabetes Mellitus;Diabetic mouse;Diestrus;differential expression;Down-Regulation;epigenetic regulation;ESR1 gene;Estrogen Receptor 2;Estrogens;Estrus;Etiology;Event;Exhibits;Female;gastrointestinal;Gastrointestinal Motility;Gastrointestinal Transit;Gastroparesis;Goals;GPER gene;Health;Histone Acetylation;Histone Deacetylase;Histone H3;Homeostasis;Hormonal Change;Impairment;insight;Knockout Mice;Knowledge;Lysine;male;Mediating;Membrane;Menstrual cycle;Methylation;Molecular;motility disorder;Mus;Muscle function;Muscle relaxation phase;Neurons;novel therapeutics;Nuclear Receptors;Obesity;Oxidative Stress;Oxidative Stress Induction;Pathway interactions;Pattern;Peripheral;Phase;Pregnancy;Prevalence;Proestrus;promoter;Promoter Regions;Protein Isoforms;Public Health;receptor expression;Receptor Gene;Regulation;Relaxation;Reporting;Research Proposals;response;Role;selective expression;Serotonin;sex;Sex Bias;sexual dimorphism;Signal Pathway;Signal Transduction;Smooth Muscle;STIM1 gene;Stomach;Testing;transcriptome sequencing;Vascular Smooth Muscle;Woman;women versus men

PROJECT_TITLE: Gender Bias in Gastrointestinal Motility in Health and Diabetes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-A(90)]


NIH_SPENDING_CATS: Bioengineering;Networking and Information Technology R&D (NITRD)

ORG_CITY: CHICAGO

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE  This project concerns the development and application of multiscale computer simulation methods to study key biomolecular processes in the cell involving membranes, membrane proteins, cytoskeleton filaments, and cytoskeleton-associated proteins. The specific systems to be studied have been implicated in a wide range of cellular phenomena pertinent to disease, including endo- and exo-cytosis, cellular trafficking, centronuclear myopathy, cancer, Alzheimer’s disease, cell invasion, and virus budding. 1

PI_NAMEs: VOTH, GREGORY A. (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Actin-Binding Protein;Actins;Alzheimer's Disease;amphiphysin;Area;Back;Behavior;Binding;Biological;Capsid Proteins;Cell division;Cell membrane;Cell Physiology;Cells;Cellular biology;Centronuclear myopathy;Coat Protein Complex I;Collaborations;Collection;Complex;Computer Simulation;computer studies;Computing Methodologies;Consultations;Coupled;Coupling;Cytoskeletal Filaments;Cytoskeletal Proteins;Cytoskeleton;Development;Disease;Dynamin;Endocytosis;Exocytosis;Filament;Filopodia;Free Energy;Funding;Generations;Goals;Grain;Grant;Growth;Hand;Immune response;Infection;innovation;Invaded;Length;Letters;Lipids;Machine Learning;Malignant Neoplasms;Mediating;Membrane;Membrane Lipids;membrane model;Membrane Proteins;Methodology;Methods;Microfilaments;Modeling;Molecular;Molecular Conformation;molecular dynamics;molecular modeling;monomer;Morphology;Movement;nano;Nature;novel;Organelles;Paper;Peripheral;Play;Preparation;Process;profilin;protein protein interaction;Proteins;Publishing;recruit;Research;Research Personnel;Role;Sampling;self assembly;Signal Transduction;simulation;Site;Solvents;spatiotemporal;System;Time;trafficking;United States National Institutes of Health;Universities;vasodilator-stimulated phosphoprotein;Virginia;virtual;Virus;Work

PROJECT_TITLE: Multiscale Computer Simulation of Key Biomolecular Processes in the Cell


NIH_SPENDING_CATS: Biotechnology;Digestive Diseases;Genetics;Infectious Diseases;Liver Disease;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE A unique feature of Plasmodium vivax biology is that, after hepatocyte infection, a fraction of sporozoites do not initiate genome replication and schizogony but instead form hypnozoites, non-replicating stages that persist within hepatocytes for weeks, months or even years after the primary infection. In this application we will identify the parasite molecular drivers of hypnozoite formation and persistence and host hepatocyte factors that impact hypnozoite formation and persistence. The findings of this application might lead to the identification of new parasite-targeted and host-targeted therapeutics that prevent relapsing malaria infection.

PI_NAMEs: KAPPE, STEFAN HI (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Anti-malarials;Biological;Biology;Blood;Cells;Cellular biology;Clinical;Complex;Culicidae;Data;Development;enhancer-binding protein AP-2;Environment;Epidemiology;Erythrocytes;Event;Feeds;Frequencies;Gene Deletion;Gene Expression;Gene Expression Profiling;Gene Transfer Techniques;Genes;Genome;Goals;Growth;GRP94;Hepatocyte;Host Defense;Human;humanized mouse;In Vitro;Infection;insight;Integration Host Factors;knock-down;Knock-out;Knowledge;Laboratories;Liver;liver infection;Malaria;malaria infection;Mediating;Messenger RNA;Metabolism;Modeling;Molecular;Monkeys;mouse model;Mus;National Institute of Allergy and Infectious Disease;overexpression;Parasites;pathogen;Pathogenicity;Persons;Phase;Phenotype;Plasmodium;Plasmodium vivax;Primary Infection;Process;Recombinants;Regulation;Relapse;relapse prevention;Reporter Genes;Research;response;Rodent;Role;Saimiri;Salivary Glands;Shapes;Small Interfering RNA;Source;Sporozoites;stress granule;symptom treatment;System;targeted treatment;Techniques;tool;transcription factor;Transfection;transgene expression;Transgenic Organisms;Translational Repression;vector control;Vivax Malaria;Work

PROJECT_TITLE: Parasite and host cell factors involved in the formation and persistence of Plasmodium vivax hypnozoites


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: NARRATIVE  The heart's upper chambers, the atria, and its lower chambers, the ventricles, contain fundamentally dis- tinct types of muscle cells, and are affected by different types of disease. One common and severe disease specific to the atria is atrial fibrillation, which occurs in over 9% of older individuals. This proposal will investi- gate the mechanisms that maintain atrial muscle cell gene expression, and perturbation of these mechanisms that cause atrial fibrillation, resulting in new insights into the causes of atrial diseases such as atrial fibrillation.

PI_NAMEs: PU, WILLIAM TSWENCHING (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Adult;Affect;Affinity;Age Years;Arrhythmia;Atrial Fibrillation;Binding;biochip;Biological Assay;Biotinylation;Cardiac;Cardiac Myocytes;Cardiovascular system;Cells;ChIP-seq;Chromatin;combinatorial;Data;Dependovirus;Development;Disease;Dissection;dosage;Dose;Enhancers;EP300 gene;Etiology;experimental study;functional genomics;GATA4 gene;Gene Expression;Gene Expression Regulation;Gene Mutation;gene regulatory network;Gene Silencing;gene therapy;Gene Transduction Agent;Genes;Genetic;Genetic study;Genetic Transcription;genome wide association study;genomic locus;Goals;Heart;Heart Atrium;heart function;Homeostasis;Human Genetics;human old age (65+);in vivo;insight;Knock-out;Knowledge;Link;loss of function;Machine Learning;Maps;Measurement;Measures;Mechanical Stress;Metabolic stress;Molecular;Morphology;mosaic;Mus;Muscle Cells;muscle enhancer factor-2A;Mutagenesis;Mutation;Nodal;novel;novel strategies;Older Population;organ growth;Pathogenesis;Persons;Phenotype;Physiological;Population;Precipitation;Predisposition;Prevalence;prevent;programs;Reagent;Regulation;Regulatory Element;Reporter;Reproducibility;Research Proposals;Risk;Signal Transduction;stem;Techniques;Testing;Therapeutic;tool;Transcription Coactivator;transcription factor;Variant;Ventricular;Work

PROJECT_TITLE: Genetic regulation of atrial gene expression in development and disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-R(02)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Genetics;Human Genome;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Opioid Use Disorder (OUD) is a debilitating condition for which we have an incomplete knowledge of pathobiological processes. A better understanding of these processes in key affected cell types will lead to the development of better therapeutic targets. The goals of this project are to perform single cell studies across OUD-relevant mouse brain regions under various opioid exposure paradigms, in order to identify candidate OUD driver genes, pathways and cell types, and to test the causal involvement in OUD of the candidates identified.

PI_NAMEs: ALVAREZ, VERONICA A;HEIMAN, MYRIAM  (contact);KELLIS, MANOLIS

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Acute;addiction;Addictive Behavior;advanced analytics;Affect;analytical tool;Animals;approach behavior;Area;Behavior;Behavioral;Brain;Brain region;Candidate Disease Gene;candidate identification;causal variant;cell type;Cells;Cellular Structures;Chronic;Communities;complex data;Corpus striatum structure;Data;Data Analyses;Dependence;Development;differential expression;Dimensions;Dissection;Dopamine;dopamine system;Dorsal;epigenomics;experimental group;Gender;Genes;Goals;Human;In Situ Hybridization;in vivo;Knowledge;Mediating;Methods;Midbrain structure;Minor;Molecular;Molecular Profiling;Morphine;mouse model;mu opioid receptors;multimodal data;Mus;Nature;Neuroglia;Neurons;novel;Nucleic Acid Regulatory Sequences;Nucleus Accumbens;Opiate Addiction;Opioid;opioid exposure;opioid use;opioid use disorder;pars compacta;Pathway interactions;Pattern;Pharmacotherapy;Phenotype;Play;Process;Proteins;Protocols documentation;Resolution;response;Rewards;RNA;Rodent;Role;Sampling;Self Administration;single-cell RNA sequencing;Societies;Specificity;Stimulus;striosome;substance use;Substance Use Disorder;Substantia nigra structure;Testing;therapeutic target;transcriptomics;Transgenic Mice;translating ribosome affinity purification and RNA-sequencing;Validation;Ventral Tegmental Area;Viral;Withdrawal

PROJECT_TITLE: Single-Cell Dissection of Ensembles and Cell Types Mediating Opioid Action in the Rodent Brain


ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Rheumatoid arthritis (RA) is a common joint disease characterized by loss of mobility and chronic pain, in which currently available therapies remain without effect in 30-70% of the patients, suggesting a critical need for identification of new therapeutic avenues. We discovered that the engulfment and cell motility protein-1 (ELMO1) contributes to disease development in mouse models of RA by facilitating recruitment of immune cells called neutrophils into the joints, where they contribute to inflammation and bone degradation. In this proposal, we will delineate the mechanisms by which ELMO1 regulates neutrophil recruitment into joints, which could lead to the discovery of new targets for therapeutic development in rheumatoid arthritis.

PI_NAMEs: ARANDJELOVIC, SANJA  (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Actins;Address;Adhesions;Affect;Alleles;Anti-Bacterial Agents;Arthritis;arthropathies;Attenuated;Bacteria;Biochemical;Biology;bone;bone erosion;Cell Line;cell motility;Cell surface;cell type;Cells;chemokine;Chronic Disease;chronic pain;Circulation;Collagen;Collagen Arthritis;Communities;CRISPR/Cas technology;Cytoskeleton;Data;Development;diagnostic tool;Disease;Disease Resistance;disorder control;Etiology;Event;Exhibits;ezrin;Genes;Genetic Transcription;HL60;Human;Immune;Impairment;improved;in vivo;Infectious Arthritis;Inflammation;Inflammatory Arthritis;inhibitor;Injections;innovation;Integrins;Introns;ITGAM gene;Joints;K/BxN model;Knowledge;L-Selectin;Leukocytes;Lung;Lymphocyte;Mass Spectrum Analysis;Mediating;microbial;migration;Minor;Modeling;moesin;Molecular;Molecular Biology;mouse model;Mus;neutrophil;Neutrophil Activation;Neutrophil Infiltration;new therapeutic target;novel diagnostics;novel strategies;novel therapeutics;Pain;pathogen;Pathogenicity;Pathology;Patients;peripheral blood;Peritoneum;Peritonitis;Phagocytosis;Population;Post-Translational Protein Processing;programs;Proteins;radixin protein;recruit;Resolution;response;Rheumatoid Arthritis;Role;SELL gene;Serum;Signal Transduction;Staphylococcus aureus;Stimulus;Symptoms;Synovial Fluid;Synovial joint;Synovitis;Testing;Therapeutic;therapeutic development;therapeutic target;Tissues;tool;transcriptomics;Transfection;Zymosan

PROJECT_TITLE: Understanding A Molecular Cascade That Drives Neutrophil Mediated Pathology In Arthritis

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


NIH_SPENDING_CATS: Genetics;Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: PHILADELPHIA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: NARRATIVE In contrast to mammals, non-mammalian vertebrates including zebrafish have retained a remarkable capacity for spontaneous CNS regeneration. This proposal takes advantage of the zebrafish system to identify mechanisms that promote regrowth of injured spinal cord axons.

PI_NAMEs: GRANATO, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Adult;Animal Model;Animals;Astrocytes;Axon;axon regeneration;Axotomy;Cadherins;candidate selection;cell regeneration;cell type;Cells;Central Nervous System;central nervous system injury;Complement;compound 30;Data;Development;Dystroglycan;EGF gene;Environment;experimental study;Foundations;Functional Regeneration;Gene Silencing;Genes;Genetic;Growth;Hour;in vivo;in vivo regeneration;Injury;Knowledge;Lasers;Left;Length;Libraries;live cell imaging;Mammals;Masks;Modeling;Molecular;Molecular Genetics;Molecular Target;mRNA Expression;mutant;Natural regeneration;Nerve Regeneration;neurodevelopment;Neuroglia;Neurons;Oligodendroglia;optic nerve regeneration;Pathway interactions;peripheral nerve regeneration;Phenotype;planar cell polarity;Play;premature;Process;receptor;Recovery;regenerative;regenerative growth;Reporting;Resolution;Role;Siblings;Signal Pathway;Signal Transduction;Site;small molecule;Spinal Cord;Spinal cord injury;spinal cord regeneration;Synapses;System;Testing;Time;tool;Transgenic Organisms;treatment strategy;Vertebrates;Zebrafish

PROJECT_TITLE: Molecular genetic mechanisms of spontaneous spinal cord regeneration

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR]


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Leukemia patients harboring AML1/ETO fusion protein achieve complete remission initially, but many of them relapse and die. This project aims to understand the ways in which AML/ETO contributes to leukemogenesis. Findings will inform intervention strategies for leukemia therapy.

PI_NAMEs: LIU, SHUJUN  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute;Acute Myelocytic Leukemia;acute myeloid leukemia 1 protein;acute myeloid leukemia cell;Address;AML1-ETO fusion protein;Binding;Binding Sites;Biochemical;Biological;Biological Markers;cell growth;Cells;chemotherapy;Chimeric Proteins;Clinical;clinical efficacy;cofactor;cytokine;Disease;Disease Progression;Disease remission;DNA Methylation;DNA Sequence Alteration;DNMT3a;driver mutation;drug testing;druggable target;Environment;Epigenetic Process;Genes;Genetic Transcription;Goals;Growth;HIF1A gene;Hormones;Hyperactivity;Hypoxia;Hypoxia Inducible Factor;improved;In Vitro;in vivo;inhibitor;innovation;insight;Intervention;Investigation;leukemia;leukemia treatment;Leukemic Cell;leukemic stem cell;leukemogenesis;Link;Literature;Malignant Neoplasms;Mediating;Mediator;Medicine;Molecular;molecular pathology;mouse model;Nature;new therapeutic target;normoxia;novel;novel therapeutics;Oncogenic;Outcome;Pathogenesis;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;pharmacologic;Positioning Attribute;predictive signature;Prognosis;Prognostic Marker;promoter;Proteins;Recurrence;Recurrent disease;Refractory;Relapse;relapse patients;Research;response;Role;RUNX1 gene;Signal Transduction;t(8;21)(q22;q22);targeted treatment;Techniques;Testing;Therapeutic;Therapeutic Agents;therapeutic biomarker;therapeutic development;Therapeutic Effect;Therapeutic Index;therapy outcome;Time;transcription factor;Transcription Initiation;Transcriptional Regulation;Transgenic Mice;Transgenic Organisms;Treatment Protocols;Work

PROJECT_TITLE: The Role of HIF1A-DNMT3A axis in AML1/ETO-Driven Acute MyelogenousLeukemia

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Genetics;Neurosciences;Rare Diseases

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE Schwann cells are neural crest derived cells whose primary function is the support and protection of neurons in the peripheral nervous system, and abnormal function of specific sub-populations of these cells can lead to abnormal sensory or motor function, or to tumors. Rac1 is a signaling molecule that functions broadly in Schwann cells, and my laboratory has generated a new mouse model in which the protein is abnormally activated in this cell type and interferes with the formation of normal populations of mature cells. In this pilot project, we will perform single cell analysis to begin to elucidate how the unregulated activation of this protein in all Schwann cells alters both the form and function of distinct populations of mature Schwann cell subtypes.

PI_NAMEs: DEDHIA, PRIYA HARAKH (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Ablation;Abnormal Cell;Address;Adopted;Affect;afferent nerve;Alleles;Animals;Applications Grants;Atrial myxoma with lentigines;Axon;Benign;Biological Models;Biology;C Fiber;Cell Communication;cell growth;Cell Physiology;Cell Proliferation;cell type;Cells;Charcot-Marie-Tooth Disease;Cyclic AMP-Dependent Protein Kinases;Data;Defect;Development;Disease;Embryonic Development;Environment;Esthesia;Exhibits;Family;Fiber;Functional disorder;Future;Human;improved;in vivo;Individual;Inherited;Knowledge;Laboratories;Location;Mediating;Modeling;Molecular;Monomeric GTP-Binding Proteins;Morphology;Motor;mouse model;Mus;mutant;Myelin;Myelin Sheath;neoplastic cell;Nerve;nerve damage;Neural Conduction;Neural Crest Cell;Neurilemmoma;Neurofibromatoses;Neurofibromin 2;Neurons;NF1 gene;Nociception;Outcome;Pain;pain perception;Pathway interactions;Patients;Peripheral;Peripheral Nervous System;Peripheral Nervous System Malignant Neoplasms;Phenotype;Physiological;Pilot Projects;Play;Population;Process;Proliferating;Proprioception;protein activation;Proteins;response;rho;Role;Schwann Cells;Sensory;Signal Pathway;Signal Transduction;Signaling Molecule;single cell analysis;single-cell RNA sequencing;Structure;Supporting Cell;Symptoms;Syndrome;Touch sensation;Transcript;transcriptome;transcriptomics;transmission process;tumor;tumorigenesis;Work

PROJECT_TITLE: Single cell transcriptomics of nerves that lack Remak bundles

STUDY_SECTION: CMBG

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


ED_INST_TYPE: SCHOOLS OF OSTEOPATHIC MEDICINE

NIH_SPENDING_CATS: Chronic Pain;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy

ORG_CITY: BIDDEFORD

ORG_NAME: UNIVERSITY OF NEW ENGLAND

ORG_STATE: ME

PHR: PROJECT NARRATIVE Intractable pain is a major clinical challenge that poses a heavy societal burden and is driving a national controversy over the use of potentially dangerous opioid analgesics. This project explores novel endogenous mechanisms by which mitochondrial function regulates sensory neuron sensitization and excitability in preclinical models of acute and chronic inflammatory and neuropathic pain. Experiments proposed here will use mild mitochondrial uncoupling compounds as pharmacological tools to manipulate mitochondrial function in sensory neurons, and will test their efficacy as novel anti-nociceptive agents.

PI_NAMEs: MOLLIVER, DEREK C (contact)

PROGRAM_OFFICER_NAME: GREENWELL, THOMAS

PROJECT_TERMS: 2,4-Dinitrophenol;Acute;Acute inflammatory pain;Acute Pain;Affect;Afferent Neurons;allodynia;American;Analgesics;Animals;antinociception;ATP Synthesis Pathway;Attenuated;Automobile Driving;behavior measurement;Behavioral;Bioenergetics;Biological Assay;Buffers;Cell Differentiation process;Cell Line;Cells;Cessation of life;Chronic inflammatory pain;chronic pain;chronic painful condition;Clinical;Coupled;Dangerousness;Data;Development;Diabetes Mellitus;Dinitrophenols;Dissociation;dorsal horn;Dose;Drug Targeting;Drug usage;electrical property;Electrophysiology (science);experimental study;Female;fluorescence imaging;Gene Deletion;Genus Hippocampus;Glycolysis;healthy aging;Human;Hyperalgesia;Hypersensitivity;improved;In Vitro;in vivo;Inflammation;Inflammatory;inflammatory pain;injured;Injury;innovation;Intractable Pain;male;Measures;Mechanics;Mediating;Membrane Potentials;Messenger RNA;Metabolic;Mitochondria;mitochondrial membrane;mitochondrial metabolism;Modeling;Molecular;Mus;Nerve Crush;nerve injury;Neurodegenerative Disorders;neuronal excitability;Neurons;Neuropathy;Nociceptors;novel;Opioid Analgesics;overexpression;oxidation;Oxidative Stress;Pain;pain chronification;Pain management;Pain Measurement;pain relief;painful neuropathy;patch clamp;Pharmaceutical Preparations;pharmacologic;Phosphoproteins;Physiological;Pre-Clinical Model;prescription opioid;Production;Property;Protein Isoforms;Proteins;Reactive Oxygen Species;Receptor Signaling;Regulation;Reporting;Respiration;response;RNA;Rodent;sciatic nerve;Sensory Ganglia;Signal Pathway;Signal Transduction;societal costs;Spinal Ganglia;Stress;Testing;therapeutic evaluation;tissue injury;tool;transcriptome sequencing;Transgenic Mice;TRPV1 gene

PROJECT_TITLE: Mitochondrial Regulation of Nociceptor Function

STUDY_SECTION: NOMD

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


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Estrogen;Genetics;Women's Health Research

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Advanced breast cancers of the most common type (Estrogen Receptor (ER) positive) initially respond to hormonal therapy, but then become resistant to further therapy. As they invade, breast cancers shed cells into the bloodstream (Circulating Tumor Cells; CTCs), which we have been able to culture repeatedly in the laboratory during the course of therapy, providing an exceptional resource to better understand acquired drug resistance. Using these patient-derived cell cultures, we propose to apply sophisticated functional genomic and chemical proteomic technologies to characterize and ultimately overcome the most common, and least well understood, mechanism of acquired resistance to hormonal therapy, namely the complete loss of ER expression in breast cancers that were initially ER positive.

PI_NAMEs: HABER, DANIEL A. (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: acquired drug resistance;Address;advanced breast cancer;Binding;Biopsy;Blood Circulation;Blood specimen;Breast;cancer cell;Cell Culture Techniques;Cell Line;Cell model;Cell Survival;Cells;Chemicals;Chemistry;Chromatin;Clinical Treatment;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;CRISPR screen;CRISPR-mediated transcriptional activation;crosslink;Cultured Tumor Cells;Cysteine;Data;Dependence;Drug resistance;drug resistance development;Drug Targeting;Endocrine;Epigenetic Process;epigenetic regulation;ESR1 gene;Estrogen receptor positive;Functional dependence;functional genomics;Funding;Genes;genome-wide;Genomics;Goals;Heterogeneity;hormone receptor-positive;hormone therapy;In Vitro;in vivo;individual patient;inhibitor;Intervention;Invaded;Knock-out;Laboratories;Libraries;Ligands;Malignant Breast Neoplasm;Malignant Neoplasms;Mass Spectrum Analysis;Microfluidic Microchips;Microfluidics;Modeling;Molecular;Mutation;Neoplasm Circulating Cells;Neoplasm Metastasis;neoplastic cell;new therapeutic target;Oncogenic;Outcome;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;PIK3CA gene;Predisposition;preservation;prevent;Proliferating;Property;protein expression;Proteins;Proteome;Proteomics;Refractory;Resistance;Resources;restoration;Sampling;screening;Signal Transduction;Source;Technology;Testing;tool;tumor;Tumor Cell Line;tumorigenic;Woman

PROJECT_TITLE: Modeling Metastasis and Acquired Drug Resistance Using Circulating Tumor Cells

STUDY_SECTION: MCTA

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Immunization;Infectious Diseases;Networking and Information Technology R&D (NITRD);Prevention;Rare Diseases;Vaccine Related

ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: This research measures vulnerability to emerging and endemic infectious diseases in space and time. By measuring vulnerability to outbreaks before they occur, this work can reduce outbreak response times and help prevent outbreaks. The methods and tools developed will be generalizable and adaptable.

PI_NAMEs: BHARTI, NITA  (contact);ROBINSON, ANTHONY CHRISTIAN

PROGRAM_OFFICER_NAME: JESSUP, CHRISTINE

PROJECT_TERMS: Behavior;Biology;Collaborations;Communicable Diseases;comparison intervention;data quality;Decision Support Systems;Democratic Republic of the Congo;Dimensions;Disease;Disease Outbreaks;disorder prevention;Ebola;Elements;Emerging Communicable Diseases;Environment;Epidemiology;Geography;graduate student;Health;health data;Human;Immunization;improved;indexing;Interdisciplinary Study;Intervention;Link;Measles;Measures;Methods;mHealth;Modeling;Morbidity - disease rate;mortality;outbreak control;outbreak response;Output;pathogen;Pattern;Population;Population Dynamics;prevent outbreaks;Prevention;Province;Public Health;Reaction Time;Recurrence;Research;response;Seasons;spatiotemporal;System;Targeted Research;Testing;theories;Time;tool;transmission process;usability;Vaccination;Visual;Visualization;Work

PROJECT_TITLE: Measuring human behavior and ecological dimensions of pathogen transmission for outbreak control and prevention


NIH_SPENDING_CATS: Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: DALLAS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative This study aims to determine the role of a particular growth factor in sensory neuron viability, axonal regeneration, and potentially neuronal regeneration in the periphery. Success in these aims will influence the development of treatment strategies for peripheral nerve injuries and degenerative diseases.

PI_NAMEs: LAI, HELEN  (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: adenovirus mediated delivery;Adult;adult neurogenesis;adult stem cell;Affect;Afferent Neurons;Alleles;Area;Autocrine Communication;Axon;axon regeneration;Cell Lineage;Cell Proliferation;Cell secretion;Cell Survival;cell type;Cells;Central Nervous System;Classification;Degenerative Disorder;Development;Distal;Enterobacteria phage P1 Cre recombinase;experimental study;Exploratory/Developmental Grant;Foundations;Future;gain of function;Generations;Genetic;Goals;Growth Factor;Hippocampus;IGF2 gene;in vivo;Injury;insight;Insulin-Like Growth Factor II;Label;Link;Literature;loss of function;Macrophage;mouse model;Mus;Natural regeneration;Nerve Crush;Nerve Degeneration;nerve injury;nerve stem cell;Neural Crest;neurogenesis;Neuroglia;neuron development;neuron regeneration;neuronal cell body;neuronal growth;neuronal survival;Neurons;novel;Paracrine Communication;Peripheral nerve injury;Peripheral Nervous System;Population;Process;progenitor;Proliferating;Property;regenerative;research study;Role;sciatic nerve;Sensory;Signal Transduction;somatosensory;Source;Spinal Ganglia;stem cells;stemness;Structure of choroid plexus;success;System;Testing;Therapeutic;therapy development;timeline;tool;transcription factor;treatment strategy

PROJECT_TITLE: Regenerative mechanisms of somatosensory neurons


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Orphan Drug;Prevention;Rare Diseases;Tuberculosis;Tuberculosis Vaccine;Vaccine Related

ORG_CITY: ALBANY

ORG_NAME: ALBANY MEDICAL COLLEGE

PHR: PROJECT NARRATIVE Tuberculosis (TB) remains a major public health burden worldwide. An attenuated live vaccine (BCG) is currently licensed but inadequately controls the TB epidemic. The limitation in protection by this vaccine is still elusive. Therefore, a better understanding of the biological difference between TB bacilli (Mtb) and BCG is essential for generation of a more effective TB vaccine. We have demonstrated that a c-di-AMP phosphodiesterase-deficient mutant of Mtb secretes a large amount of c-di-AMP and induces a strong type I interferon (IFN-I) response in the infected macrophages. In contrast, BCG is unable to secrete c-di-AMP and is defective in IFN-I induction, even when the same gene is deleted. Interestingly, it has been reported that IFN-I links between innate and adaptive immunity, and addition of IFN-I elevates the immunogenicity of BCG. Moreover, c-di-AMP itself has been recognized as a vaccine adjuvant. Based on our understanding of the c-di- AMP-mediated signaling network in Mtb and BCG, we will construct novel recombinant BCG strains that secrete c-di-AMP and induce IFN-I in the vaccinated host. It is very likely that this approach will improve BCG's efficacy. Additionally, the result of this proposal will provide fundamental insights into vaccine strategy against other pathogens. Therefore, the outcomes from this proposal will largely impact public health.

PI_NAMEs: BAI, GUANGCHUN  (contact)

PROGRAM_OFFICER_NAME: EICHELBERG, KATRIN

PROJECT_TERMS: adaptive immunity;Adjuvant;Animals;Antibodies;Antigens;Attenuated Vaccines;Bacillus;Bacterial Physiology;BCG Vaccine;Biological;CD8-Positive T-Lymphocytes;Cells;cytokine;design;Dinucleoside Phosphates;draining lymph node;Enzyme-Linked Immunosorbent Assay;Epidemic;epidemic response;Etiology;experimental study;Generations;Genes;Goals;Homeostasis;Immune response;immunogenicity;improved;In Vitro;Infant;insight;Interferon Type I;Knowledge;Licensing;Link;Listeria monocytogenes hlyA protein;Lung;Lung infections;Macrophage;Mediating;Modeling;Mus;mutant;Mycobacterium bovis;Mycobacterium tuberculosis;Mycobacterium tuberculosis antigens;Natural Immunity;novel;novel strategies;novel vaccines;Outcome;pathogen;Pathogenesis;pathogenic bacteria;Periodicity;phosphoric diester hydrolase;Play;Population;Prevention;Production;Proteins;Public Health;rBCG;Recombinant Vaccines;regional difference;Reporting;response;Role;Signal Transduction;Signaling Molecule;Spleen;T cell response;Testing;Tuberculosis;Tuberculosis Vaccines;Vaccinated;Vaccination;vaccination against tuberculosis;Vaccine Adjuvant;vaccine efficacy;vaccine platform;vaccine strategy;Vaccines;Virulence;Virulent;Western Blotting

PROJECT_TITLE: A novel c-di-AMP-based recombinant BCG vaccine


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Tuberculosis

ORG_COUNTRY: UNITED KINGDOM

ORG_FIPS: UK

ORG_NAME: UNIVERSITY OF CAMBRIDGE

ORG_ZIPCODE: CB2 1TN

PHR: This project will investigate the granuloma, the hallmark immune aggregates in tuberculosis. It aims to understand how the granuloma cells die, thereby favoring growth of the TB bacteria.

PI_NAMEs: RAMAKRISHNAN, LALITA  (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Acceleration;Antigen-Antibody Complex;Apoptosis;Bacteria;Bioenergetics;Biology;Cause of Death;Cells;cohort;cytokine;Death Domain;Defect;Disease;Electron Transport;Event;extracellular;FRAP1 gene;Funding;Genetic;Genetic Screening;Genetic Variation;Genus Mycobacterium;Glean;Goals;Granuloma;Growth;Host resistance;Human;hypoxia inducible factor 1;imaging capabilities;Immune;Immune response;Immune signaling;Induction of Apoptosis;innate immune pathways;insight;lens;Lysosomes;Macrophage;Mediating;Medical;Membrane Potentials;Meningeal Tuberculosis;Metabolic;microbicide;Mitochondria;mitochondrial dysfunction;mitochondrial membrane;Modeling;Molecular;Morbidity - disease rate;mortality risk;mutant;mycobacterial;Mycobacterium Infections;Mycobacterium marinum;Mycobacterium tuberculosis;Natural Immunity;Necrosis;Necrosis Induction;Oxidative Phosphorylation;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Patients;Pattern;pharmacologic;Predisposition;prevent;programs;Proteins;Reactive Oxygen Species;Research;resistance factors;RIPK1 gene;Risk Factors;risk variant;Role;Signal Induction;Signal Transduction;Structure;Testing;TNF gene;transmission process;Tuberculosis;tuberculosis granuloma;Tumor Necrosis Factor Receptor;Variant;Virulence;Virulence Factors;Work;Zebrafish

PROJECT_TITLE: Host responses to Mycobacterium infection in Zebrafish

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


PHR: Lay Summary We have identified a pathway involving a protein termed Notch4 that plays a critical role in asthma by disrupting the function of immune regulatory T (Treg cells) that normally inhibit lung inflammation and we also found that different agents that aggravate asthma including allergens, pollutant particles and respiratory viruses all act to activate this pathway. In this proposal, we will employ genetic mouse models and studies on blood samples of human patients with asthma to examine how Notch4 activation impairs immune tolerance and promotes asthmatic inflammation. These studies will be important in devising new therapies to treat asthmatics.

PI_NAMEs: CHATILA, TALAL AMINE (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: adaptive immune response;Address;Affect;airway inflammation;Allergens;allergic airway inflammation;Allergic inflammation;Alveolar Macrophages;Asthma;asthmatic;Automobile Driving;Biology;Blood specimen;Body mass index;Cell Physiology;Cells;Choristoma;Chronic;cohort;Coupled;Cues;cytokine;environmental change;Epigenetic Process;Evolution;Exposure to;Generations;Genetic;Growth Factor;growth factor receptor-bound protein 2;High Prevalence;Human;Immune;immune function;Immune response;Immune Tolerance;Immunologics;immunoregulation;Impairment;Individual;Industrialization;Inflammation;Inflammatory;Innate Immune Response;Interleukin-13;Interleukin-4;Interleukin-6;Licensing;Life;Life Style;Ligands;Link;Lung;Mediating;morphogens;mouse model;notch protein;novel;novel therapeutics;Obesity;obesity-associated asthma;particle;Particulate Matter;Pathogenesis;Pathology;Pathway interactions;Patients;Play;pollutant;Predisposition;Process;Production;Property;Proteins;Pulmonary Inflammation;receptor;Regulation;Regulatory T-Lymphocyte;respiratory virus;RNA;Role;Signal Transduction;Social Change;Source;Structure of parenchyma of lung;Susceptibility Gene;synergism;Th2 Cells;tissue repair;tissue-repair responses;Tissues;Variant;Viral;Viral Respiratory Tract Infection;Virus;Virus Activation;Virus Diseases;WNT Signaling Pathway

PROJECT_TITLE: Genetic and Epigenetic Programming of Allergic Airway Inflammation

STUDY_SECTION: LCMI

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