NIH_SPENDING_CATS: Atherosclerosis;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE Coronary artery disease (CAD) is the leading cause of death in the United States, accounting for one in six deaths. Cardiac MRI is a non-invasive non-ionizing technique for comprehensive evaluation of CAD, but its clinical translation is hampered by lengthy exam times. In this work, we will develop and validate techniques for rapid cardiac MRI in a short exam time for comprehensive CAD assessment.

PI_NAMEs: AKCAKAYA, MEHMET  (contact)

PROGRAM_OFFICER_NAME: EVANS, FRANK

PROJECT_TERMS: 3-Dimensional;absorption;Acceleration;Accounting;accurate diagnosis;Anatomy;Angiography;artificial neural network;Award;Back;Breathing;cardiac magnetic resonance imaging;Catheters;Cause of Death;Cessation of life;Chest;Chest Pain;Clinical;clinical translation;cohort;Coronary;Coronary Angiography;Coronary Arteriosclerosis;Coronary Stenosis;cost;Data;Development;Diagnosis;diagnosis standard;Diagnostic;diagnostic tool;disease diagnosis;Evaluation;Excision;Extravasation;Gadolinium;Gatekeeping;Gold;Healthcare;Heart;heart function;high resolution imaging;Image;imaging modality;Imaging Techniques;improved;Ionizing radiation;Machine Learning;Magnetic Resonance Imaging;Medical Care Costs;Methods;Morphologic artifacts;Myocardial perfusion;Noise;non-invasive imaging;noninvasive diagnosis;novel;Patients;Perfusion;Physiological;Preparation;prevent;Procedures;Property;rapid technique;reconstruction;Resolution;revascularization;Risk;Roentgen Rays;Scanning;Scheme;Signal Transduction;Slice;Source;Stenosis;Symptoms;Techniques;temporal measurement;Testing;Time;tool;United States;Work

PROJECT_TITLE: Rapid Comprehensive Cardiac MRI Exam for Diagnosis of Coronary Artery Disease

STUDY_SECTION: EITA

STUDY_SECTION_NAME: Emerging Imaging Technologies and Applications Study Section[EITA]


ADMINISTERING_IC: HS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF PHARMACY

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: Los Angeles

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHARMACOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: Project Narrative Enacted in 1986, the Emergency Medical Treatment and Labor Act (EMTALA) imposed a duty to treat – prior to EMTALA emergency departments could legally turn away patients with emergency conditions based upon ability to pay. Despite its intent to protect vulnerable populations, there is indirect evidence suggesting that EMTALA as currently enforced may exacerbate health disparities, because some hospitals have adapted to EMTALA in ways that might paradoxically reduce access to or quality of emergency care. Understanding whether EMTALA enforcement is associated with measurable changes in access to quality emergency care is needed to inform efforts to enhance and improve the statute.

PI_NAMEs: SEABURY, SETH  (contact);TERP, SOPHIE

PROGRAM_OFFICER_NAME: KARACA, ZEYNAL

PROJECT_TITLE: Impact of EMTALA on Access to and Quality of Emergency Care

STUDY_SECTION: HSVR

STUDY_SECTION_NAME: Healthcare Systems and Values Research[HSVR]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE To date, there are no available in vivo methods to distinguish critical sub-types of frontotemporal lobar degeneration (FTLD) that may be amenable to treatment. We have recently described iron-rich cortical pathology in FTLD, showing distinct laminar distributions associated with underlying proteinopathies. We will develop novel, iron-sensitive MRI protocols to monitor and diagnose FTLD pathologies in vivo, supporting future treatment trials that target individual proteinopathies.

PI_NAMEs: TISDALL, MATTHEW DYLAN (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: Address;Advanced Development;Age;Alzheimer's disease related dementia;Anatomy;Atrophic;Autopsy;Behavior;Biological;Biological Markers;Blood;Brain;brain iron;Cerebral cortex;Clinical;clinical care;Collaborations;Dedications;Dementia;Deposition;Detection;Development;Diagnosis;Diagnostic Specificity;diagnostic value;digital;Disease;disease diagnosis;Disease Progression;disorder subtype;economic impact;Exhibits;FDA approved;Frontotemporal Dementia;Frontotemporal Lobar Degenerations;Future;Genotype;Gliosis;Goals;Grain;gray matter;Histology;Histopathology;Human;Image;imaging biomarker;imaging modality;in vivo;Individual;Iron;Joints;Laboratories;Language;Language Disorders;Magnetic Resonance Imaging;Maps;Measures;Methods;Monitor;motor deficit;motor symptom;Mutation;mutation carrier;Nerve Degeneration;Neurodegenerative Disorders;neuroimaging;neuropathology;non-invasive monitor;noninvasive diagnosis;novel;Pathologic;Pathology;Pathway interactions;Patients;Pattern;Phenotype;Physiologic pulse;Process;Protocols documentation;Recommendation;recruit;Research;Resources;Sampling;Severities;Social Impacts;Spatial Distribution;symposium;Symptoms;Syndrome;targeted imaging;targeted therapy trials;tau Proteins;tool;treatment trial;ultra high resolution;volunteer;white matter;Work

PROJECT_TITLE: Imaging Iron-Rich Pathology to Monitor and Diagnose FLTD Subtypes


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: COLLEGE PARK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because abnormal decision-making is a hallmark of many psychiatric disorders. This proposal is particularly relevant to the aims of NIDA because it will substantially improve our insight into how neural signals in key learning and decision-making circuits develop in normal animals and how they are altered in animals exposed to cocaine. Improving our understanding of the neural, epigenetic, and computational mechanisms underlying the decision-making process will provide a better working knowledge of how we behave normally and how this circuit is affected by chronic drug use, which will aid in the development of more effective treatment solutions and diagnostic strategies for such psychiatric disorders.

PI_NAMEs: ROESCH, MATTHEW R (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: addiction;Affect;Amygdaloid structure;Animals;Anterior;Area;Attention;Attenuated;Behavior;Behavioral;Brain;Brain region;career;Cell Count;Choice Behavior;Chronic;cingulate cortex;Cocaine;cocaine exposure;cocaine self-administration;cocaine use;Cognitive;Conflict (Psychology);Corpus striatum structure;Cues;Data;Decision Making;Development;diagnostic strategy;Diffusion;dopaminergic neuron;Dorsal;Drug usage;effective therapy;Enzymes;Epigenetic Process;Event;executive function;Exhibits;Expectancy;experimental study;Funding;Goals;Habits;HDAC5 gene;Impairment;improved;innovation;insight;Insula of Reil;Knowledge;Lateral;Lead;Learning;Mental disorders;Midbrain structure;Modeling;National Institute of Drug Abuse;neural;neural correlate;neural repair;neuromechanism;Neurons;neurotransmission;Nucleus Accumbens;Odors;optogenetics;Outcome;overexpression;Pharmaceutical Preparations;Play;Policies;Population;Predictive Value;Process;psychologic;Public Health;Publishing;Rattus;Reaction Time;Relapse;Research;response;Response to stimulus physiology;restoration;reward anticipation;Rewards;Sampling;Self Administration;Shapes;Signal Transduction;Stimulus;Structure;System;Task Performances;Testing;Time;Uncertainty;Update;Ventral Tegmental Area;Work

PROJECT_TITLE: Restoration and Further Assessment of the Actor-Critic Circuit and Connected Areas After Cocaine Self-Administration

STUDY_SECTION: BRLE

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: LOUISVILLE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: Alphaviruses, such as Sindbis virus, Chikungunya virus, and Venezuelan Equine Encephalitis virus are significant threats to public health. Alphaviral infection in otherwise healthy individuals may result in severe disease- including persistent severe multi-joint arthritis, viral encephalitis, and death. This proposal seeks to characterize the importance of a novel noncapped viral RNA in regards to the establishment of viral infection and pathogenesis, for the purpose of improving the understanding of alphaviral biology to identify innovative therapeutic strategies.

PI_NAMEs: SOKOLOSKI, KEVIN JOSEPH (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Address;Affect;Alpha Virus;Alphavirus Infections;Anti-viral Agents;Anti-viral Therapy;Arthritis;Attenuated;Binding;Biology;Brain;Cell Line;Cessation of life;Chikungunya virus;Clinical;combinatorial;Cytoplasm;Defect;defined contribution;Development;Disease;Disease Outbreaks;effective therapy;Environment;Event;expectation;Failure;Gene Expression;genomic RNA;Genomics;Growth;Histologic;Immune response;Impairment;improved;In Vitro;in vivo;Individual;Infection;Innate Immune Response;innovation;Integration Host Factors;Interferons;Internal Ribosome Entry Site;Invertebrates;Joints;Kinetics;knowledge base;knowledgebase;Link;Modeling;Molecular;Molecular Analysis;Morbidity - disease rate;mortality;mutant;Nature;neuroinflammation;novel;Nucleocapsid;particle;pathogen;Pathogenesis;Pathologic;Process;Production;Proteins;Proteomics;Public Health;Reporting;Research;response;RNA;RNA chemical synthesis;Role;Ross river virus;Sindbis Virus;Structure;Techniques;Testing;Therapeutic;tissue culture;tissue/cell culture;transcriptomics;vaccine strategy;Vaccines;vector-borne pathogen;Venezuelan Equine Encephalitis Virus;Viral;Viral Encephalitis;Viral Genes;Viral Pathogenesis;viral RNA;Virion;Virulence;Virus Diseases;Virus Replication;Wild Type Mouse;Work

PROJECT_TITLE: Comprehensive Definition of the Critical Role(s) of the Alphaviral Noncapped Genomic RNAs to Infection and Pathogenesis

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: HOUSTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Vancomycin is currently the drug of choice and the most important antibiotic for the treatment of CDI. However, C. difficile strains with decreased susceptibility to vancomycin have emerged in the patient population. The goal of this project is to establish the proportion and characterize the genetic elements responsible for vancomycin non-susceptibility in C. difficile isolates in patients from two geographically distinct locations, and assess the impact of vancomycin non- susceptibility on clinical outcomes.

PI_NAMEs: DARKOH, CHARLES  (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: African;alternative treatment;Antibiotic Therapy;antibiotic-associated diarrhea;Antibiotics;base;Biochemical;Cessation of life;Classification;Clinical;Clostridium difficile;Communicable Diseases;cost;Diarrhea;Elements;Epidemiology;Exhibits;Feces;Foundations;Gene Cluster;Genes;Genetic;genetic element;genome sequencing;Genomics;Geography;Goals;Guidelines;Healthcare;Homologous Gene;Hospitals;Incidence;Infection;insight;Intervention;Kenya;Life;Location;Mediating;Mediator;Metronidazole;mortality;North America;Oral;Outcome;pathogen;patient population;Patients;Peptidoglycan;Pharmaceutical Preparations;Predisposition;Prevention strategy;prospective;Public Health;Pulsed-Field Gel Electrophoresis;Recommendation;Recurrence;recurrent infection;Reporting;Research;Resistance;resistance mechanism;resistant strain;Ribotypes;Severity of illness;Societies;stool sample;Texas;Treatment Failure;treatment response;Vancomycin;Vancomycin Resistance;whole genome;Work

PROJECT_TITLE: Characterizing Vancomycin-Resistant C. difficile Strains at Two Geographically Distinct Locations

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

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Lung;Rare Diseases

ORG_CITY: AUGUSTA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) carry an unacceptably high level of mortality which results from the fundamental lack of effective pharmacological therapies. A common feature of ALI is the loss of endothelial barrier function in the pulmonary circulation, but a multitude of mechanisms underlie the pathological changes that contribute to pulmonary edema and complicates the investigation. This Project is focused on the novel role of cytoplasmic actions of histone deacetylase, HDAC9, in endothelial barrier regulation with the goal of accelerating the development of new therapeutic approaches.

PI_NAMEs: VERIN, ALEXANDER D (contact)

PROGRAM_OFFICER_NAME: ESPINOZA GRANDON, INGRID CECILIA

PROJECT_TERMS: Acceleration;Acute Lung Injury;Acute Respiratory Distress Syndrome;Adherens Junction;Affect;Agonist;analog;Antibiotics;Bacterial Toxins;beta catenin;Blood Vessels;Cell Nucleus;Clinical;Complex;Cytoplasm;Cytoplasmic Protein;Cytoskeletal Proteins;Cytosol;Data;Deacetylation;Development;Endothelial Cells;Endothelium;Escherichia coli;Functional disorder;GAB1 gene;Gene Modified;genetic corepressor;Genetic Transcription;Goals;Gram-Negative Bacteria;Gram-Negative Bacterial Infections;HDAC9 gene;HGF gene;Histone Deacetylase;Human;improved;In Vitro;in vivo;Inflammation;Inflammatory Response;Intensive Care;Investigation;Knockout Mice;Link;Lipopolysaccharides;Lung;lung microvascular endothelial cells;Mediating;Modeling;Molecular;mortality;Mus;novel;novel therapeutic intervention;Nuclear;Nuclear Export;Nuclear Import;overexpression;Pathologic;Patients;Permeability;pharmacologic;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;plakoglobin;Property;protective effect;Protein Dephosphorylation;Protein phosphatase;Proteins;Pulmonary Circulation;Pulmonary Edema;pulmonary function;receptor;Regulation;Respiratory distress;Role;Sepsis;Signal Transduction;Source;Syndrome;Testing;Transgenic Mice;Vascular Endothelium;Vascular Permeabilities

PROJECT_TITLE: HDAC9 nuclear/cytoplasmic shuttling in pulmonary vascular endothelial barrier regulation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-A(05)]


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Contraception/Reproduction;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_DEPT: OBSTETRICS & GYNECOLOGY

PHR: Project Narrative This randomized controlled intervention maternal (BIPOC).  trial addresses social and structural inequities to reduce SMM and mortality in the most at-risk patients – those that self-identify as Black, indigenous and people of color Specifically, our intervention will implement and evaluate anintegrated, multi-level maternity care home model (MCHM) aimed at reducing SMM among a group of BIPOC patients. With this trial, we aim to test our central hypothesis that a patient-centered MCHM will address the gap in social, structural, and health system factors that contribute to disparities for our most vulnerable patients, thereby reducing SMM.

PI_NAMEs: LEVINE, LISA DANIELLE;SRINIVAS, SINDHU K (contact)

PROGRAM_OFFICER_NAME: TYUS, NADRA

PROJECT_TERMS: Address;Birth;Black Populations;Black race;Black, Indigenous, People of Color;Blood;care coordination;care costs;care delivery;care systems;Caring;Cities;clinical practice;Collaborations;Color;Complication;cost;Cost Savings;Developed Countries;Disparity;Education;Effectiveness;effectiveness evaluation;effectiveness testing;effectiveness/implementation trial;Emergency Situation;Ensure;Equity;ethnic disparity;Event;experience;Failure;Health;Health Resources;Health system;Healthcare;high risk;Hospitals;implementation determinants;implementation facilitators;improved;Indigenous;Individual;Inequity;Institution;Insurance;Intervention;intrapartum;Life;Maternal Health Services;maternal morbidity;Maternal Mortality;Medicaid;Medical;Mental Health;Methods;Modeling;Morbidity - disease rate;mortality;Outcome;Outsourcing;patient centered medical home;patient home care;patient oriented;Patients;people of color;Persons;Philadelphia;post pregnancy;postpartum care;Postpartum Period;Pregnancy;prenatal;Prenatal care;pressure;Primary Care;programs;Provider;racial disparity;Randomized;Randomized, Controlled Trials;referral services;Reporting;Resources;Review Committee;Risk;screening;secondary outcome;service delivery;Service delivery model;severe maternal morbidity;social;Social Conditions;social determinants;social health determinants;Social outcome;Social Work;standard of care;structural determinants;structural health determinants;Substance Use Disorder;success;Surveys;Testing;Text;Translating;United States;uptake;Visit;White Women;Wit;Woman

PROJECT_TITLE: Enhance Trial-Enriched Holistic Care to Eradicate Maternal Morbidity


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics;HIV/AIDS;Infectious Diseases;Mental Health;Neurosciences

PHR: Narrative. Characterization of the CNS reservoir and empiric testing of novel cure strategies require physiologically relevant animal models of HIV persistence in the brain. Here, we propose to integrate major advances from our groups in transmitted/founder (TF) SHIV NHP models and AAV-delivered CRISPR/Cas9 editing to delineate key features of the CNS reservoir and assess a promising approach to eradicative cure. In coordinated NHP experiments, we will use barcoded, macrophage-tropic TF SHIV.D to elucidate the mechanisms of CNS persistence and test the efficacy of global and myeloid-specific CRISPR/Cas9 gene editing to cure HIV.

PI_NAMEs: BAR, KATHARINE JUNE (contact);BURDO, TRICIA HELEN

PROGRAM_OFFICER_NAME: RAO, VASUDEV RAMACHANDRA

PROJECT_TERMS: adenovirus mediated delivery;Aftercare;Animal Model;Antibodies;Autologous;Bar Codes;Binding;Biodistribution;Biological Assay;Biological Availability;Brain;Brain region;CCR5 gene;CD4 Positive T Lymphocytes;cell type;Cells;Clinic;Clonality;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;Data;efficacy evaluation;efficacy testing;endonuclease;Evolution;Excision;experimental study;gene delivery system;gene editing technology;gene therapy;gene-editing approach;Genes;Genetic;Genome;Guide RNA;HIV;HIV-1;Human;Immunohistochemistry;improved;in vitro activity;in vivo;in vivo evaluation;Infection;insight;Interruption;Kinetics;Lymphoid Tissue;Macaca mulatta;Macrophage;Measures;Mediating;memory CD4 T lymphocyte;Modeling;Molecular;monocyte;Myelogenous;Neuropathogenesis;nonhuman primate;novel;Pathogenesis;Pattern;Physiological;pre-clinical;predictive modeling;Prevention;Proviruses;Safety;simian human immunodeficiency virus;SIV;Source;System;Testing;Time;Tissues;transmission process;Tropism;Variant;Viral;Viral Genome;viral rebound;Viral reservoir;Virus;virus host interaction;Virus Latency

PROJECT_TITLE: Novel macrophage-tropic transmitted/founder SHIV model of CNS persistence to evaluate CRISPR/Cas9 gene editing


ADMINISTERING_IC: CA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Gene Therapy;Genetics;Human Genome;Immunotherapy;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: STANFORD

ORG_DEPT: PEDIATRICS

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE While chimeric antigen receptor T cell (CAR-T) therapies have revolutionized treatment options in a variety of pediatric cancers, CAR-Ts have provided little benefit to metastatic or relapsed solid tumor patients, in part because of inadequate CAR-T expansion. To understand the potential causes of poor CAR-T expansion, this research proposal will evaluate the effect of costimulatory domain and pre-apheresis chemotherapy on solid tumor patient CAR-T expansion and efficacy. Results will identify predictors or drivers of CAR-T efficacy and provide a platform to improve future CAR-T treatment options for children with solid tumors.

PI_NAMEs: RAMAKRISHNA, SNEHA  (contact)

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Advisory Committees;Affect;Aftercare;Agammaglobulinaemia tyrosine kinase;Antigens;ATAC-seq;B-Cell Acute Lymphoblastic Leukemia;Biological Assay;Biology;Blood Component Removal;CAR T cell therapy;career;CD28 gene;Cell Line;Cells;Cellular immunotherapy;chemotherapy;Child;Childhood Solid Neoplasm;chimeric antigen receptor T cells;Clinical;Clinical Research;Clinical Trials;Clonality;cytokine;cytotoxicity;Data;Data Analyses;design;diffuse midline glioma;Dimensions;Epigenetic Process;exhaustion;experience;Failure;fitness;Foundations;Funding;Future;Gene Expression Profile;Hematologic Neoplasms;Immune;Immunology procedure;immunoregulation;Immunotherapy;improved;In Vitro;innovation;insight;Learning;Malignant Childhood Neoplasm;Malignant Neoplasms;manufacture;Mediating;Memory;Mentors;Mentorship;Modeling;Molecular;Molecular Profiling;multidimensional data;Mus;novel;Osteosarcoma;Outcome;overexpression;OX40;Pathway interactions;patient variability;Patients;Pediatric Oncology;Pharmaceutical Preparations;Phenotype;pre-clinical;Pre-Clinical Model;Prior Chemotherapy;Production;profiles in patients;Relapse;Research;Research Proposals;response;Sampling;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;T cell receptor repertoire sequencing;T memory cell;T-Cell Activation;T-Lymphocyte;TCF Transcription Factor;Technology;Testing;Training;transcription factor;Transcription Factor AP-1;transcriptome;transcriptome sequencing;transcriptomics;translational research program;tumor;Tumor Antigens;tumor immunology;Tyrosine Kinase Inhibitor;Up-Regulation;Work;Xenograft Model;young adult

PROJECT_TITLE: Defining Pre-treatment Correlates of Patient GD2 CAR T Cell Exhaustion and Memory Using Multi-Dimensional Immune Profiling

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Autism;Biotechnology;Brain Disorders;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative This project is relevant to NIH’s mission by providing fundamental knowledge regarding cellular and circuit basis underlying SCN2A deficiency-related neuronal hyperexcitability and seizures. Knowledge gained through the completion of this project provides a foundation for the development of novel therapeutic interventions to alleviate seizures in SCN2A related human disorders.

PI_NAMEs: YANG, YANG  (contact)

PROGRAM_OFFICER_NAME: MATOS GALICIA, HEIDI YANICE

PROJECT_TERMS: Action Potentials;Address;Adult;Affect;ASD patient;autism spectrum disorder;Brain;Brain region;Cells;Central Nervous System;Child;comorbidity;Corpus striatum structure;Data;density;Development;Disease;Down-Regulation;efficacy evaluation;Electroencephalography;Electrophysiology (science);Epilepsy;epileptiform;Foundations;gain of function;gene therapy;Genetic;Genetic study;hippocampal pyramidal neuron;Human;in vivo;innovation;insight;Knock-out;Knockout Mice;Knowledge;Length;loss of function;Medial;Mission;Modeling;Molecular;mouse model;Mus;neural network;neuronal excitability;Neurons;novel;novel therapeutic intervention;novel therapeutics;Outcome;patch clamp;Pentylenetetrazole;Pharmacology;Phenotype;Physiology;Potassium Channel;Predisposition;Prefrontal Cortex;Research Personnel;restoration;SCN2A protein;Seizures;Signal Transduction;Slice;Sodium Channel;Technology;Testing;Therapeutic Intervention;therapeutically effective;TNFSF5 gene;transcriptome sequencing;United States National Institutes of Health;Variant;voltage;Work

PROJECT_TITLE: Neuronal hyperexcitability and seizures in a Scn2a deficient mouse model

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ORG_CITY: IOWA CITY

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative Bacteroidetes are major components of the intestinal microbiota linked to many human diseases. The proposed research will identify interbacterial responses among Bacteroides spp. important for intestinal colonization and persistence. Better understanding of commensal bacterial interactions will ultimately guide development of targeted therapeutics.

PI_NAMEs: BOSCH, DUSTIN E (contact)

PROJECT_TERMS: Affect;Anatomy;antagonist;Applications Grants;Bacteria;bacterial genetics;Bacteriology;Bacteroides;Bacteroides fragilis;Bacteroides thetaiotaomicron;Bacteroidetes;Board Certification;Carbohydrates;career;career development;cell behavior;Cells;Clinical;Clinical Pathology;Coculture Techniques;Communication;Communities;Complex;Development;Development Plans;Diet;Disease;DNA;Doctor of Medicine;Doctor of Philosophy;Ecosystem;Educational workshop;Elements;Environment;experimental study;Faculty;Funding;gastrointestinal;Genome;Germ-Free;Gnotobiotic;Goals;Grant;Growth;gut colonization;gut microbiota;Human;human disease;Immunity;Individual;Intestines;K-Series Research Career Programs;Lateral;Leadership;Link;Mannans;Mediating;meetings;Mentored Clinical Scientist Development Award (K08);Mentorship;Microbiology;microbiota composition;Molecular;mouse model;Mus;novel;nuclease;Pathology;Physicians;Polysaccharides;Process;professor;Proteins;Proteomics;Research;Research Infrastructure;Research Personnel;Resource Development;response;Role;Scientist;Shapes;skills;Starch;Structural Protein;symbiont;System;targeted treatment;Technology;Testing;Therapeutic;Toxin;Training;Translating;Transmembrane Transport;United States National Institutes of Health;Writing;Yeasts

PROJECT_TITLE: Contact-dependent interbacterial responses modulate intestinal colonization by Bacteroides species

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


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

ORG_CITY: RICHMOND

ORG_DEPT: CHEMISTRY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE Micro-RNAs (miRNAs) are promising biomarkers for cancer staging, diagnosis, prognosis, and therapeutics, however, their clinical applications are greatly limited by the inconsistent results among studies and lack of high-confidence detection methodologies. We will develop and optimize a single-molecule detection platform for simultaneous detection of endogenous miRNAs in cancer samples and develop a microfluidic chip to enable a speedy analysis of multiple samples in under 1 hour. While the detection platform is generic to miRNA biomarkers of different cancers, we will test our platform with a set of diverse preclinical triple-negative breast cancer (TNBC) samples from TNBC-carrying patient-derived xenograft (PDX) mice.

PI_NAMEs: DHAKAL, SOMA  (contact)

PROGRAM_OFFICER_NAME: PATRIOTIS, CHRISTOS F

PROJECT_TERMS: Address;Antibodies;Attention;Benchmarking;Binding;Biological;Biological Assay;Biological Markers;Buffers;cancer biomarkers;cancer diagnosis;cancer therapy;Cells;circulating microRNA;Clinical;clinical application;clinical diagnosis;clinical practice;cost;design;Detection;detection assay;detection method;detection platform;detection sensitivity;Development;Diagnosis;Diagnostic Neoplasm Staging;Diagnostic Specificity;Disease;Disease Progression;DNA;DNA Sequence;Dyes;Early Diagnosis;Enzymes;Exhibits;Face;Fluorescence;Fluorescence Microscopy;Fluorescence Resonance Energy Transfer;fluorophore;Goals;Health;Hour;Human;human disease;innovation;interest;Label;Malignant Neoplasms;Measures;Methodology;Methods;Microfluidic Microchips;microRNA biomarkers;MicroRNAs;miRNA expression profiling;Monitor;multiplex detection;Mus;mutant;Mutation;Nature;Noise;novel strategies;Nucleic Acids;overexpression;Pathway interactions;patient derived xenograft model;Patient-derived xenograft models of breast cancer;Patients;Physiology;Point Mutation;pre-clinical;Process;Prognosis;Recurrence;Reproducibility;Research;Resources;response;Risk;Risk Assessment;RNA Sequences;Role;Sampling;Scheme;Screening for cancer;sensor;Serum;Signal Transduction;single cell technology;single molecule;Speed;Staging;synthetic construct;Techniques;Technology;technology platform;Testing;Therapeutic;TP53 gene;Translating;treatment response;triple-negative invasive breast carcinoma;tumor;tumor growth;Tumor Suppressor Genes;Tumor Tissue;tumor xenograft;Uncertainty;Work

PROJECT_TITLE: Single-Molecule High-Confidence Detection of miRNA Cancer Biomarkers


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative The goal of this research effort is to develop versatile new methods for the preparation of compounds of biomedical significance. Through a multidisciplinary approach, improvements in the speed, efficiency, selectivity, and cost of introducing structural subunits that impact the biological properties and function of complex structures will be developed.

PI_NAMEs: MONTGOMERY, JOHN  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Health Services;Neurodegenerative;Neurosciences;Primary Health Care

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Delivering coordinated, comprehensive care to older adults with Alzheimer's Disease and Related Dementias (ADRD) is challenging. The goal of this proposal is to examine the frequency and consequences of simultaneous enrollment in more than one care management program and to develop and implement a practical primary care based intervention to facilitate collaboration across care management programs for older adults with ADRD. This proposal will support the career development of Dr. Stephanie Nothelle who aims to develop embedded interventions to improve care delivery for older adults with ADRD.

PI_NAMEs: NOTHELLE, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: RADZISZEWSKA, BARBARA

PROJECT_TERMS: acceptability and feasibility;Accident and Emergency department;Acute;Address;Aging;Alzheimer's disease related dementia;Area;Baltimore;Behavioral;Bioinformatics;care coordination;care delivery;career development;Caring;Case Manager;Clinic;Collaborations;collaborative approach;collaborative care;comorbidity;Complex;Comprehensive Health Care;Data;Data Set;Dementia;dementia care;design;Development;Discipline;Disease Management;Enrollment;Environment;experience;Family Caregiver;feasibility testing;Fostering;Frequencies;Funding;Future;Goals;Grant;Health;health information technology;Health system;Heart failure;Hospital Departments;Hospitals;improved;Individual;Intervention;intervention refinement;Interview;Lead;Link;Managed Care;Managed Care Programs;Matched Group;Medical;medical specialties;Mentors;multidisciplinary;novel;older adult;Older Population;Operative Surgical Procedures;Outcome;Persons;pilot test;population health;Prevalence;Primary Care;primary care clinician;programs;Publications;Research;Research Methodology;Research Personnel;Resources;Role;Scholarship;Services;Social support;Statistical Methods;Structure;Symptoms;systematic review;Testing;therapy design;Training Activity;Work

PROJECT_TITLE: Primary care based collaborative approach to care management for older adults with dementia

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Clinical Aging Study Section[NIA-C]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: SAN FRANCISCO

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Anesthesiologists play a critical role in the treatment of a wide range of health issues for diverse patient populations in multiple clinical arenas. The breadth of the field affords anesthesiologists the capacity to contribute enormously to basic, translational and clinical research and to push forward discovery, knowledge and care of patients in the operating room, intensive care units, pain medicine clinics, and other perioperative settings. This training grant program will provide the next generation of anesthesiologists and allied scientists with rigorous training in biomedical research so that they can bring more scientific discoveries to patients, and carefully document the safety, efficacy, and importance of the discoveries.

PI_NAMEs: HELLMAN, JUDITH  (contact)

PROGRAM_OFFICER_NAME: PAUL, MOUSHUMI

PROJECT_TERMS: Anesthesia procedures;Research Training

PROJECT_TITLE: Comprehensive Anesthesia Research Training


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases;Tickborne Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: Phoenixville

ORG_NAME: ADVAC THERAPEUTIC, LLC

PHR: PROJECT NARRATIVE Vector-borne viral pathogens pose a global health risk to humans. SFTSV is a highly pathogenic, emerging bunyavirus that causes viral hemorrhagic disease in humans, with spillover potential. This project will leverage results with a 1st generation vaccine vector for development of an effective preventative therapeutic for SFTSV that may also aid in pandemic preparedness against other novel disease threats.

PI_NAMEs: BATES, PAUL  (contact);COCKA, LUIS

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Andes Virus;Animal Model;Animals;Antibodies;Antibody Response;Antigens;Biological Assay;Blood;Case Fatality Rates;Cell membrane;Cell surface;Cells;China;clinically relevant;cross immunity;Death Rate;design;Development;Disease;Disease Outbreaks;Distant;Domestic Animals;Dose;Ebola;Ebola Vaccines;Ebola virus;Engineering;experience;Far East;Fc Receptor;Fever;Foundations;Future;future outbreak;Gene Order;Generations;Genes;Genome;Genomic Segment;Geography;global health;Glycoproteins;Golgi Apparatus;Hantavirus;Health;Heartland virus;Hemorrhage;Human;human pathogen;Immune;Immune response;Immunity;Immunization;Immunocompromised Host;immunogenic;immunogenicity;improved;In Vitro;in vivo;Infection;Influenza;Injections;Interferon Receptor;Japan;Kinetics;Korea;Lassa;Learning;Leukopenia;Licensing;manufacture;Modification;Molecular;mouse model;Mucous Membrane;Mus;Mutate;Mutation;neutralizing antibody;novel;Orthobunyavirus;outbreak concern;pandemic preparedness;particle;pathogen;pathogenic virus;Pathogenicity;Phase;Positioning Attribute;pre-clinical;Production;prophylactic;protective efficacy;protein expression;Proteins;Readiness;Recombinants;research and development;Respiratory syncytial virus;response;Reverse engineering;reverse genetics;Rift Valley Fever;Risk;RNA;RNA Viruses;Severe Fever with Thrombocytopenia Syndrome Virus;Site;Surface;T cell response;T-Lymphocyte;Therapeutic;tick-borne;transmission process;Vaccinated;Vaccination;Vaccine Production;Vaccines;vector;vector tick;vector vaccine;vector-borne;Vesicular stomatitis Indiana virus;Vietnam;Viral;Viral Genome;Viral Hemorrhagic Fevers;Viral reservoir;Viral Vaccines;Virion;Virus;Virus Diseases;Virus Replication;Wild Animals;Work;Zoonoses;zoonotic spillover

PROJECT_TITLE: Development of recombinant VSV vaccines for emerging bunyaviruses

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


NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Immunotherapy;Infectious Diseases;Malaria;Neurosciences;Rare Diseases;Vector-Borne Diseases

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: NARRATIVE Blood-brain barrier disruption, brain swelling and edema were recently defined as biomarkers of disease severity in the first clinical studies using MRI in patients suffering from cerebral malaria. In this proposal, we use novel transgenic mice to present evidence that CD8 T cell induced lethal blood-brain barrier disruption is initiated through priming by discrete antigen presenting cell types. In this proposal, we will this “nature verses nurture” hypothesis pertaining to how CD8 T cells induce BBB disruption in vivo using the Plasmodium berghei ANKA (PbA) model of experimental cerebral malaria.

PI_NAMEs: JOHNSON, AARON J (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Ablation;Acute;Adoptive Transfer;Antigen-Presenting Cells;Biological Markers;Blood Vessels;blood-brain barrier disruption;Brain;Brain Edema;brain endothelial cell;C57BL/6 Mouse;CD11c Antigens;CD8-Positive T-Lymphocytes;cell type;Cells;Cerebral Malaria;Clinic;Clinical;Clinical Research;Complication;conditional knockout;Core Facility;Cytometry;cytotoxicity;Data;Dendritic Cells;Deposition;drug resistance development;Drug usage;Edema;Employment;Etiology;Experimental Models;experimental study;Fibrinogen;Generations;Goals;Hemorrhage;Human;human disease;human model;Image;Immune;Immunity;in vivo;Infection;Infiltration;Inflammation;Inflammatory;innovation;Investigation;ITGAX gene;Knockout Mice;Knowledge;Location;Lymphocyte Subset;Macrophage;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Malaria;Mediating;Methodology;MHC Class I Genes;Microglia;Modeling;Morbidity - disease rate;mouse model;Mus;Nature;Nervous System Disorder;neuropathology;novel;Parabiosis;Pathology;Patients;perforin;Phase;Plasmodium berghei;Plasmodium falciparum;Population;Process;programs;Proteins;Protocols documentation;Publishing;Reporting;Research;Resistance;Resistance development;response;Role;Severity of illness;System;T cell response;T cell therapy;Testing;Therapeutically Targetable;Tight Junctions;Tissues;Transgenic Mice;Transgenic Organisms;Vascular Endothelial Growth Factors;Vascular Permeabilities;Work

PROJECT_TITLE: CD8 T cell mediated disruption of Blood Brain Barrier Tight Junctions

STUDY_SECTION: BINP

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


NIH_SPENDING_CATS: Bioengineering;Clinical Research;Immunization;Infectious Diseases;Malaria;Malaria Vaccine;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

PHR: PROJECT NARRATIVE Immunity to malaria naturally develops in those repeatedly infected by malaria parasites, but is a complex process involving different parts of the immune system and therefore poorly understood. In this proposal, we will broadly profile the immune systems of children and adults living in a malaria endemic area over multiple points in time, building state-of-the-art computational models to learn how infection affects the immune system and how this eventually leads to protection against malaria.

PI_NAMEs: BUTTE, ATUL J;GREENHOUSE, BRYAN R (contact);JAGANNATHAN, PRASANNA

PROGRAM_OFFICER_NAME: BREEN, JOSEPH J

PROJECT_TERMS: acquired immunity;Acute;adaptive immune response;Adult;Affect;Africa South of the Sahara;Age;age group;Animals;Antibodies;Antibody Response;Antiparasitic Agents;Area;attenuation;Bayesian Network;Biological;Biological Assay;Blood;Cell Physiology;Child;Chronic;Clinic;Clinical;cohort;Cohort Studies;Complex;Computer Models;Data;Development;Disease;Educational workshop;epidemiologic data;Evolution;experimental study;Exposure to;Falciparum Malaria;Fever;flexibility;Gene Expression Profiling;Genetic;Growth;Human;Immune;Immune response;Immune system;Immunity;Immunologics;Individual;Infection;Inflammatory;Inflammatory Response;Innate Immune Response;insight;Intervention;Laboratories;Learning;longitudinal dataset;Malaria;Malaria Vaccines;Measurement;Modeling;Modernization;Morbidity - disease rate;mortality;Outcome;Parasites;Participant;pathogen;Phenotype;Plasmodium falciparum;Process;Property;public repository;Recurrence;recurrent infection;Research;response;Time;Uganda;Vaccine Design;Vaccines;Validation;Visualization;web site

PROJECT_TITLE: Computational models of naturally acquired immunity to falciparum malaria


ORG_CITY: SANTA BARBARA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: Morrissey Project Narrative: (3 sentences) Cells measure, add, and subtract stimuli to determine when to respond and when to remain quiescent. This project is focused on how macrophages measure ‘Eat me’ and ‘Don’t eat me’ signals to set a threshold for triggering phagocytosis and inflammation. Our goal is to understand the biochemical and biophysical mechanisms underlying this decision, which may serve as the foundation for future studies manipulating macrophage signaling in a disease context.

PI_NAMEs: MORRISSEY, MEGHAN A (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Affect;Binding;Biochemical;Biophysical Process;Cell Survival;Cells;Data;density;Disease;Dose;Eating;Environment;Fc Receptor;Foundations;Future;Goals;Immunoglobulin G;Inflammation;Ligands;Macrophage;MAPK Signaling Pathway Pathway;Measures;Molecular;NF-kappa B;Output;pathogen;Pattern;Phagocytosis;rapid detection;Reaction;receptor;response;Signal Pathway;Signal Transduction;Stimulus

PROJECT_TITLE: Signal Integration during Phagocytosis

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


ORG_CITY: BROOKINGS

ORG_NAME: SOUTH DAKOTA STATE UNIVERSITY

ORG_STATE: SD

PHR: Project Narrative The proposed project is relevant for public health because therapeutic antibodies are one of the most promising class of drugs for treatment of autoimmune diseases, infections, cancers and modulation of immune function. This work is relevant to the mission of NIH in that it will advance the critically needed understanding of how therapeutic antibodies function thereby providing new guiding principles for therapeutic design.

PI_NAMEs: HOPPE, ADAM DAVID (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Actins;Adoptive Transfer;Agonist;anti-CD20;Antibodies;Antibody Therapy;antibody-dependent cellular phagocytosis;Autoimmune Diseases;B-Lymphocytes;Binding;Biological Assay;Bone Marrow;CCND1 gene;CD47-SIRPα;CD8B1 gene;CDW52 gene;Cells;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR screen;cytokine;Data;Data Set;defined contribution;Dependence;design;Disease remission;effective therapy;Environment;Functional dependence;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;gene function;Genes;Genetic Transcription;Goals;Human;human tissue;humanized mouse;IL4 gene;Immune;immune function;Immunocompetent;Immunoglobulin G;Immunologics;immunoregulation;Immunosuppression;improved;in vivo;in vivo Model;Infection;Inflammatory;inhibiting antibody;innovation;Interferon Type II;Interferons;Intervention;Knock-out;Ligands;Lymphocyte;Lymphoma;Macrophage;Macrophage Activation;Malignant - descriptor;Malignant Neoplasms;Mediating;Membrane;Metabolic;Methods;Microscopy;Mission;Modeling;Molecular;Monoclonal Antibody Therapy;mouse model;Mus;Myeloid Cells;novel;Pathway interactions;patient response;Patients;Peripheral Blood Mononuclear Cell;Pharmacotherapy;programs;Public Health;receptor;receptor expression;receptor function;Receptor Signaling;Regulation;Regulatory T-Lymphocyte;response;rituximab;screening;Signal Transduction;Spleen;Stimulator of Interferon Genes;Surface;System;Systems Biology;T-Lymphocyte;Testing;Therapeutic;Therapeutic antibodies;Therapeutic Effect;therapeutic target;tissue repair;transcriptome sequencing;transcriptomics;Translating;Translations;United States National Institutes of Health;Variant;whole genome;Work

PROJECT_TITLE: The immune regulation of macrophage antibody dependent cellular phagocytosis


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biomedical Imaging;Clinical Research;Coronaviruses;Coronaviruses Diagnostics and Prognostics;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Infectious Diseases;Lung;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative Leveraging expertise in innovative lung imaging and growing experience in COVID-19 clinical care at Columbia University Irving Medical Center (CUIMC) in New York City, we propose to apply state-of-the-art dual energy computed tomography to define the lung vasculature and parenchyma in 200 patients hospitalized for COVID- 19 at CUIMC and 100 matched controls. To strengthen our investigation into microvascular mechanisms of COVID-19 lung injury, we will correlate imaging findings at 3-12 months and 27-36 months post-COVID hospital discharge with biomarkers of inflammation, hypercoagulability, and complement activation. This will provide important insights on the development, progression, and prognosis of post-COVID chronic lung disease that will be suitable to guide post-COVID care and risk stratification, suggest targets for therapeutic interventions, and inform policies for risk mitigation and public health in the COVID-19 era.

PI_NAMEs: OELSNER, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: 2019-nCoV;Acute;acute COVID-19;Adult;Age;Alveolar;angiogenesis;Biological Markers;Blood capillaries;blood perfusion;Blood Vessels;Blood Volume;Body mass index;C-reactive protein;Carbon Monoxide;Caring;cell injury;Cessation of life;Chronic lung disease;Clinical;clinical care;Cohort Studies;Complement;Complement 5a;Complement Activation;complement pathway;contrast enhanced;COVID-19;COVID-19 impact;COVID-19 mortality;COVID-19 pandemic;COVID-19 sequelae;COVID-19 survivors;Critical Care;Defect;Deposition;design;Development;Diagnosis;Diffuse;Diffusion;Endothelial Cells;Endothelium;Epithelial Cells;Epithelium;Ethnic Origin;Etiology;experience;Fibrin fragment D;Fibrosis;follow-up;Glass;Health;Heterogeneity;Histopathology;Hospitalization;Hospitals;Hypoxemia;Image;imaging approach;improved;in vivo;Infiltration;Inflammation;innovation;Inpatients;insight;Interleukin-6;Intubation;Investigation;Long COVID;Longterm Follow-up;Lung;Lung Capacity;lung imaging;lung injury;Measurement;Measures;Mechanical ventilation;Medical center;Modeling;multi-ethnic;Neighborhoods;New York City;Participant;Patients;Pattern;Perfusion;Phenotype;Policies;post-COVID-19;posthospitalization care;Prognosis;prognostic;Protocols documentation;Public Health;Pulmonary Emphysema;Questionnaires;Race;Recording of previous events;Recovery;Regional Perfusion;Residual state;risk mitigation;risk stratification;Sampling;SARS-CoV-2 antibody;severe COVID-19;sex;Spirometry;Structure;targeted treatment;Testing;Texture;Therapeutic Intervention;Thrombophilia;Thrombus;Universities;vascular abnormality;Venous blood sampling;Visit;Work;X-Ray Computed Tomography

PROJECT_TITLE: COVID-19 Lung Microvascular and Parenchymal Sequelae (Lung-MaPS)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-C(90)]


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

ORG_NAME: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC

PHR: Anxiety disorders such as phobias, panic disorder, and generalized anxiety disorder, are often characterized by maladaptive fear responses, but mechanistic insight into underlying neurocircuit function is still incomplete. Here, we study the role of serotonin in the periaqueductal grey to understand how this major modulatory neurotransmitter can change innate fear responses in adulthood and after developmental interference. Experiments are designed to reveal causal relationships between serotonergic activity, postsynaptic neurophysiology and behavior, to improve diagnosis, prevention, and treatment strategies in psychiatry.

PI_NAMEs: ZANNI, GIULIA  (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: Acute;Address;Adult;Affect;Air Movements;Animals;Anti-Anxiety Agents;Anxiety;Anxiety Disorders;anxiety-like behavior;anxiety-related disorders;Attenuated;avoidance behavior;Behavior;behavior test;Behavioral;Behavioral Assay;Behavioral Paradigm;behavioral response;Biological Assay;Brain;career development;Coupled;Cues;Data;deep learning algorithm;design;designer receptors exclusively activated by designer drugs;Development;Development Plans;Diagnosis;Disinhibition;Drug Targeting;early life stress;Emotional;Emotions;Ensure;Ethology;Etiology;experience;Experimental Designs;Fiber;Fluoxetine;Freezing;Fright;Functional disorder;Functional Imaging;gamma-Aminobutyric Acid;Gene Silencing;Generalized Anxiety Disorder;Genetic;glutamatergic signaling;Glutamates;Goals;Growth;Harm Reduction;HTR2A gene;Human;Hyperactivity;Implant;improved;in vivo;insight;Lead;Life;maladaptive behavior;Mental disorders;Mentors;Mentorship;midbrain central gray substance;Modeling;Molecular;Monitor;mouse model;Mus;nerve supply;neural circuit;Neurons;neurophysiology;Neurosciences;Neurotransmitters;novel therapeutic intervention;Odors;optical fiber;optogenetics;Organism;Output;Panic Disorder;Pathway interactions;Pattern;pharmacologic;Phenotype;Phobias;Photometry;Population;postnatal;postsynaptic;Pregnancy;Prevention strategy;programs;Protocols documentation;Psychiatry;Reaction;receptor;Recurrence;Research;response;Risk Assessment;Risk Factors;Role;Scientist;Selective Serotonin Reuptake Inhibitor;sensor;Serotonin;Signal Transduction;stem;Stimulus;System;Techniques;Testing;Training;treatment strategy;Work

PROJECT_TITLE: Role of serotonin brain circuit in the developmental emergence ofinnate fear

STUDY_SECTION: PMDA

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Genetics;Immunotherapy;Inflammatory Bowel Disease;Microbiome

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Inflammatory Bowel Disease (IBD) is a rapidly growing health problem that already afflicts over 3 million people in the U.S. alone, causing lifelong debilitating conditions that create enormous social and economic burdens to society. This proposal investigates how T cells normally mediate immune tolerance to commensal bacteria of the gastrointestinal system during health, and how a breakdown in this process may contribute to disease. The knowledge gained from these studies will promote our understanding of IBD pathogenesis and provide novel strategies for future treatments.

PI_NAMEs: MOON, JAMES J (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: antigen-specific T cells;Antigens;Autoantigens;Bacteria;Bacterial Antigens;CD4 Positive T Lymphocytes;CD8B1 gene;Cells;Cellular biology;Clonal Deletion;Collection;commensal bacteria;commensal microbes;Complex;cytotoxic;Development;Discrimination;Disease;Economic Burden;Enteral;enteric infection;Environment;Excision;FOXP3 gene;Future;gastrointestinal system;Gastrointestinal tract structure;Goals;gut microbiota;Health;Heterogeneity;Immune;Immune response;Immune system;Immune Tolerance;Immunodominant Epitopes;Inflammatory;Inflammatory Bowel Diseases;Interleukin-10;intestinal epithelium;intraepithelial;Knowledge;Longevity;Lymphocyte;Mediating;Memory;Mus;novel strategies;Pathogenesis;Pathogenicity;Pathway interactions;Peptides;Peripheral;Persons;Phenotype;Population;Process;Property;Reagent;Regulatory Pathway;Regulatory T-Lymphocyte;Reporter Genes;Resolution;Role;Shapes;single-cell RNA sequencing;social;Societies;Sorting;Specificity;System;T cell clonality;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Therapeutic;Thymus Gland;transcriptomics;Transgenic Organisms

PROJECT_TITLE: T cell Tolerance to Enteric Commensal Bacteria

STUDY_SECTION: DHMI

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


PHR: The proposed research is relevant to public health because it will have a positive impact on developing new approaches to lessen the burden of obesity. Specifically, this project will provide new fundamental knowledge of how inflammation, particularly adipose tissue inflammation, influences skeletal muscle molecular responses to exercise. The project is relevant to the mission of NIDDK because it satisfies a critical need for understanding factors that contribute to variability in exercise response, particularly in individuals with obesity.

PI_NAMEs: LANZA, IAN R (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Abdomen;Acute;Adipose tissue;Anatomy;Attenuated;Behavioral;Biochemical;Biology;Biopsy;Blood;Cells;Chemicals;Collection;cytokine;Data;disability;Disease;Endocrine;Event;Exercise;Exercise Physiology;Exhibits;experimental study;Exposure to;Forskolin;Functional disorder;Gene Expression;Genes;Genetic;Human;Impairment;In Vitro;in vivo;in vivo imaging;Individual;Inflammation;Inflammatory;Inflammatory Response;insight;interdisciplinary approach;Ionomycin;knock-down;Knowledge;Leg;Link;Macrophage;Measurement;mechanical stimulus;Messenger RNA;Metabolic;Metabolic Diseases;Mission;mitochondrial dysfunction;Molecular;molecular phenotype;Muscle;Muscle Cells;Muscle Fibers;Muscle function;muscle physiology;Muscle Proteins;National Institute of Diabetes and Digestive and Kidney Diseases;non-invasive imaging;novel strategies;obese person;Obesity;paracrine;Participant;Pathway interactions;Persons;pharmacologic;Phenotype;Physiologic pulse;Population;Prevention;Protein Biosynthesis;protein expression;Proteomics;Protocols documentation;Public Health;Research;resistance exercise;response;Risk;Role;Signal Pathway;Signaling Protein;Skeletal Muscle;skeletal tissue;stable isotope;Stimulus;subcutaneous;Testing;Thigh structure;Tissues;TLR4 gene;tool;Tracer;Training;transcriptomics;translational study;Work

PROJECT_TITLE: Exercise Response in Humans with Obesity

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Bioengineering;Breast Cancer;Cancer;Nanotechnology;Women's Health Research

ORG_CITY: TEMPE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: Project Narrative In this proposal, our long-term goal is to develop a novel “crosslinking-based targeted therapy” for treatment of triple-negative breast cancer patients. If successful, this innovative therapy for the prevention and treatment of TNBC metastasis should have a significant impact on reducing the mortality rate in triple-negative breast cancer patients.

PI_NAMEs: CHEN, SHENGXI  (contact);CUI, XIAOJIANG

PROGRAM_OFFICER_NAME: GREENBERG, WILLIAM A

PROJECT_TERMS: 3-Dimensional;Antibodies;antibody conjugate;Antineoplastic Agents;Apoptosis;Binding;Biological Assay;Breast Cancer Cell;Breast Cancer cell line;breast cancer metastasis;Breast Cancer Patient;Breast Cancer Treatment;cancer cell;Cancer Cell Growth;Cause of Death;Cell Aggregation;cell motility;Cells;chemotherapy;Circulation;Coupled;crosslink;Death Rate;design;Disease;Distant Metastasis;DNA;Doxorubicin;Drug Delivery Systems;Drug Kinetics;Drug or chemical Tissue Distribution;effective therapy;Effectiveness;Epidermal Growth Factor Receptor;ERBB3 gene;Estrogen Receptors;Foundations;Goals;Growth;Hormone Receptor;Human;In Vitro;in vivo;Inbred BALB C Mice;Individual;Induction of Apoptosis;inhibitor;innovation;Innovative Therapy;Invaded;Malignant Breast Neoplasm;Mammary Neoplasms;Mediating;Membrane;Metabolic;Metastatic malignant neoplasm to brain;Metastatic Neoplasm to the Lung;migration;mouse model;Mus;nanoparticle;nanoparticle drug;Nanostructures;Neoplasm Metastasis;New Agents;novel;novel therapeutics;overexpression;Pharmaceutical Preparations;Pilot Projects;prevent;Prevention therapy;Primary Neoplasm;Progesterone;Progesterone Receptors;Prognosis;Protein Overexpression;Reagent;receptor;Recurrent tumor;Resistance;Safety;scaffold;Series;Site;small molecule;Subgroup;targeted agent;targeted treatment;Testing;Therapeutic;triple-negative invasive breast carcinoma;tumor growth;Western Blotting;Xenograft Model

PROJECT_TITLE: Crosslinking-based targeted therapy for triple-negative breast cancer


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Networking and Information Technology R&D (NITRD);Opioid Misuse and Addiction;Opioids;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Telehealth;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: Project Narrative Women involved in the carceral system are at an increased risk of opioid use disorder, overdose and HIV- acquisition. Given the disproportionate number of racial/ethnic minority women, carceral settings provide an opportunity to reduce racial/ethnic disparities in HIV and opioid use disorder treatment engagement by linking these women with innovative biomedical HIV prevention strategies (e.g., pre-exposure prophylaxis; PrEP) and medications for opioid use disorder (MOUD) treatment services. Providing linkage to these services using technology that provides women peer and healthcare provider support could be novel, so we propose the development and pilot testing of the PA-Links web-based app to enhance communication in an existing post- release navigation model embedded in a community-based health services organization in Pennsylvania.

PI_NAMEs: BASS, SARAH B (contact);DAURIA, EMILY F

PROGRAM_OFFICER_NAME: LEE-WINN, ANGELA EUNJI

PROJECT_TERMS: acceptability and feasibility;Access to Information;Address;Adherence;Advocate;AIDS prevention;Attitude;barrier to care;Bass;Behavior;behavioral health;care providers;Communication;Communities;community advisory board;community engagement;Community Health;Community Healthcare;Complex;Counseling;COVID-19 pandemic;Data;Decision Making;Demographic Factors;Development;Discrimination;eHealth;Enhancement Technology;ethnic disparity;Ethnic Minority Women;experience;Feedback;follow-up;formative assessment;Gender;General Population;health care availability;health care delivery;Health Personnel;Health Services;Healthcare;Hepatitis C virus;high risk;High Risk Woman;HIV;HIV Infections;HIV risk;implementation framework;implementation science;Imprisonment;improved;Individual;injection drug use;innovation;interest;Intervention;Intervention Studies;Interview;Jail;Knowledge;Link;Maps;marginalization;Marketing;Medical;medication for opioid use disorder;men;Mental Health;methadone patient;Methods;mHealth;mobile application;mobile computing;Mobile Health Application;Modality;Modeling;multidisciplinary;Needle Sharing;novel;opioid use disorder;Overdose;overdose risk;Participant;patient navigation;Patient Self-Report;Patients;peer;peer support;Pennsylvania;Perception;Pharmaceutical Preparations;Philadelphia;Pilot Projects;pilot test;pilot trial;Poverty;pre-exposure prophylaxis;Prevention strategy;preventive intervention;primary outcome;programs;prototype;Provider;racial disparity;racial minority women;racism;Randomized;Research;Research Design;Resources;Risk;Route;secondary outcome;Self Assessment;service organization;Services;Shapes;smartphone based assessment;social;social stigma;sociocultural determinant;Structure;substance abuse treatment;substance use;Substance Use Disorder;substance use treatment;Surveys;System;Techniques;Technology;Testing;therapy development;three-dimensional visualization;tool;transactional sex;treatment services;underserved community;Unsafe Sex;uptake;usability;vector;web app;web-based assessment;Woman;Women's Group;Work

PROJECT_TITLE: Development and pilot testing of a mobile health application to improve HIV prevention and substance use treatment service access among women involved in the carceral system

STUDY_SECTION: HIBI

STUDY_SECTION_NAME: HIV/AIDS Intra- and Inter-personal Determinants and Behavioral Interventions Study Section[HIBI]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Motoric Cognitive Risk syndrome (MCR) is a recently described pre-dementia syndrome, characterized by the presence of subjective cognitive complaints and slow gait that identifies people at high risk of Alzheimer’s disease and vascular dementia. Previous studies have described the epidemiology and identified modifiable risk factors for MCR. Yet, the pathogenesis of MCR is yet to be established.

PI_NAMEs: VERGHESE, JOE  (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Acceleration;Accounting;Address;Affect;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Area;Atrophic;Australia;Biological;Biological Assay;Biological Markers;Biology;Blood Vessels;Brain;Brain Pathology;Canada;cerebral microbleeds;Clinical;clinical phenotype;clinical risk;Cognition;Cognitive;cognitive testing;cohort;Communities;Complex;cost efficient;Country;Data;data harmonization;Dementia;depressive symptoms;Diagnosis;Digit structure;Elderly;Epidemiology;executive function;France;Gait;Genetic;Genetic Polymorphism;Genetic Predisposition to Disease;Geriatrics;Gerontology;gray matter;high risk;hippocampal atrophy;IL10 gene;Impaired cognition;Incidence;Individual;Inflammatory;Japan;Knowledge;Laboratories;Lacunar Infarctions;late life;Link;Longitudinal Studies;Magnetic Resonance Imaging;Microvascular Dysfunction;middle age;mild cognitive impairment;modifiable risk;Motor;motor control;multi-ethnic;Multicenter Studies;Nerve Degeneration;Neuroanatomy;neuroimaging;novel;nutrition;Obesity;older adult;Oxidative Stress;Participant;Pathogenesis;Pathway interactions;Pattern;Persons;Phenotype;Physical activity;polygenic risk score;Polygenic Traits;Prevalence;Process;Publishing;Quebec;Reporting;Risk;Risk Factors;risk prediction;Sampling;Syndrome;Testing;Thinness;Time;Vascular Dementia;White Matter Hyperintensity

PROJECT_TITLE: The biological underpinnings of Motoric Cognitive Risk syndrome: a multi-center study

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


ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE In situ vaccination is a type of cancer immunotherapy that consists of administering a treatment directly into a tumor in order to regress that tumor and initiate a systemic immune response against tumor antigens. Our preliminary data suggest that by incorporating a blocking antibody against the IL10 receptor into in situ vaccines we enhance innate immune cells' ability to (i) directly kill tumor cells and (ii) prime tumor-specific T- cells that act systemically. In experiments that will lead to clinical trials aimed at extending the lives of patients with solid cancers, we will investigate the mechanism and the generalizability of this effect.

PI_NAMEs: KHALIL, DANNY  (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: adaptive immune response;adaptive immunity;Address;Advisory Committees;Affect;Agonist;Animals;Antigen-Presenting Cells;Antitumor Response;Area;Attention;Attenuated;Bilateral;Bioinformatics;Biological Assay;Blocking Antibodies;cancer immunotherapy;Cancer Model;Cancer Patient;cancer type;career;Cells;Cellular biology;Clinical Research;Clinical Trials;cytokine;Cytotoxic T-Lymphocytes;Data;Dependence;design;Development;Disinhibition;Educational workshop;efficacy testing;exhaustion;experimental study;Feedback;Foundations;Funding;Goals;Human;Immune;immune checkpoint blockade;Immune response;Immunology;Immunotherapy;Impairment;Implant;improved;improved outcome;in situ cancer vaccination;in situ vaccination;in situ vaccine;In Vitro;in vivo Model;Innate Immune System;insight;interest;Interleukin-10;interleukin-10 receptor;Investigation;knowledge base;Laboratories;Laboratory Study;Life;Lipid A;Malignant Neoplasms;Mediating;meetings;Melanoma;Memorial Sloan-Kettering Cancer Center;Memory;Mentors;Methods;Modeling;Monoclonal Antibodies;Natural Immunity;neoplastic cell;novel;Patient-Focused Outcomes;Patients;Phenotype;Population;Positioning Attribute;preclinical study;programs;receptor;Receptor Cell;Records;Regimen;Research;Research Project Grants;Research Training;Resistance;response;Role;Scientist;skills;Solid;standard of care;statistics;System;T cell response;T-Lymphocyte;tenure track;Testing;therapeutic vaccine;TLR4 gene;TNFRSF5 gene;Training;Translating;tumor;Tumor Antigens;Tumor Immunity;tumor specificity;vaccination strategy;Work

PROJECT_TITLE: Local blockade of IL10R on innate immune cells to mediate both innate and adaptive anti-tumor immunity


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Liver Disease;Neurosciences;Skin Cancer

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: RELEVANCE TO PUBLIC HEALTH Cancer patients die of metastasis, and this advanced stage of disease is especially aggressive in metastatic melanoma. Melanoma metastasizing to distinct organs not only adapts to these organs' environment but also co-opts organ site-specific niches to thrive and evade therapies. Comprehensive study of organ-specific melanoma biology will enable a clearer understanding on the differential prognosis and therapy response associated with distinct metastatic organs.

PI_NAMEs: HUGO, WILLY  (contact)

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: anti-CTLA4;anti-PD-1;anti-PD1 therapy;Automobile Driving;Autopsy;Biological;Biology;Biopsy;BRAF gene;Brain;Cancer Patient;Cardiovascular system;Cell Compartmentation;cell growth;Cells;Cessation of life;Clinical Trials;clinically relevant;Combination immunotherapy;Data;Dependence;Disease;Disease Progression;Distant;Environment;Evolution;experience;Future;Gene Expression;Genetic;Genomics;Glean;Growth;Growth Inhibitors;Heterogeneity;Hour;Immune;immune checkpoint blockade;Immunocompetent;Immunotherapy;inhibitor;insight;Interferons;Knowledge;Lesion;Liver;Lung;Malignant Neoplasms;MAP Kinase Gene;Mediating;MEKs;Melanoma;Melanoma patient;Metastatic malignant neoplasm to brain;Metastatic Melanoma;Metastatic Neoplasm to the Bone;Metastatic Neoplasm to the Leptomeninges;Metastatic Neoplasm to the Liver;Metastatic Neoplasm to the Lung;Mitogen-Activated Protein Kinase Inhibitor;Modeling;multiple omics;Mus;Neoplasm Metastasis;neoplastic cell;neural;Neuronal Differentiation;non-genomic;Normal Cell;Normal tissue morphology;novel;Organ;Pathway interactions;Patients;Pattern;Phenotype;PIK3CG gene;pre-clinical;Prognosis;Prognostic Marker;programs;Proto-Oncogene Proteins c-akt;Public Health;Research;Research Personnel;Resistance;resistance mechanism;response;response biomarker;Role;Route;Sampling;Site;Skin;Soil;Specimen;Spleen;success;Testing;therapy resistant;Tissues;transcriptomics;treatment response;Triplet Multiple Birth;tumor;tumor growth;tumor heterogeneity;tumor microenvironment;Validation;Work

PROJECT_TITLE: Metastatic Clonal Heterogeneity and its Impact on Melanoma Therapeutic Resistance

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


NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Emphysema;Lung;Prevention;Tobacco;Tobacco Smoke and Health

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative This project will 1) continue to develop a smoking mouse model of NE+ exosome generation and disease transfer to further examine mechanisms of disease and 2) identify mechanism of attachment of human neutrophil elastase to the surface of PMN derived exosomes as a potential therapeutic target and measure the association between these NE+ PMN exosomes and disease metrics in COPD.

PI_NAMEs: GENSCHMER, KRISTOPHER R. (contact)

PROJECT_TERMS: airway obstruction;alpha 1-Antitrypsin;Alveolar;alveolar destruction;Antibodies;Binding;Biological Markers;Biology;Cells;Characteristics;chronic inflammatory disease;Chronic Obstructive Pulmonary Disease;cohort;Collagen Type I;Complex;Coughing;Development;Disease;disease model;disease phenotype;Disease Progression;Dissociation;Early identification;Excision;exosome;exposure to cigarette smoke;Extracellular Matrix;Extracellular Matrix Proteins;Future;Generations;Goals;Grant;high risk population;Human;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory;inhibitor;Integrins;Leukocyte Elastase;Link;Liquid substance;Lung;Lysine;Macrophage-1 Antigen;Measures;Membrane;Methods;Modeling;Molecular;mouse model;Mus;nanovesicle;neutrophil;never smoker;non-smoking;Paper;Pathogenesis;Pathogenicity;Pathway interactions;patient stratification;Patients;Peptide Hydrolases;Phase;Phenotype;Population;Predisposition;Production;Protamines;Protease Inhibitor;Proteoglycan;Pulmonary Emphysema;Resistance;Respiratory Failure;RIPK3 gene;Risk Factors;risk stratification;Role;Sampling;Serine Protease;Serum;Severity of illness;Shortness of Breath;Site;Smoke;Smoker;Smoking;smoking-related lung disease;Sputum;Surface;Therapeutic;therapeutic target;Trypsin;vesicular release;Work

PROJECT_TITLE: A Pathogenic Smoke Associated Neutrophilic Exosomal Pathway.

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Osteogenesis Imperfecta;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: HOUSTON

ORG_DEPT: GENETICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Osteogenesis Imperfecta (OI) is a congenital bone and craniofacial disorder that mainly affects bones with varying severity in postnatal bone regeneration and repair, but how normal or defective structural components of collagen in OI regulate bone stem/progenitor cells are essentially unknown. In this project, we seek to define the in vivo characteristics and function of periosteal and bone marrow SSPCs in clinically relevant OI mouse models and we also propose to define key OI matrix factors that regulate periosteal and bone marrow SSPC function and improve bone healing. The success of the proposed studies will lead to new biological and clinical insights into SSPC function under OI pathophysiological conditions.

PI_NAMEs: LEE, BRENDAN ;PARK, DONGSU  (contact)

PROGRAM_OFFICER_NAME: VERBRIDGE, SCOTT SPENCER

PROJECT_TERMS: Acceleration;Affect;Animal Model;Biological;bone;Bone Diseases;bone healing;Bone Injury;Bone Marrow;Bone Regeneration;bone repair;bone strength;Breathing;Cell Count;Cell Physiology;Cell Proliferation;Cells;Characteristics;Clinical;Clinical Trials;clinically relevant;Collagen;combinatorial;Combined Modality Therapy;cortical bone;craniofacial;Craniofacial Abnormalities;craniofacial bone;craniofacial disorder;Defect;Deformity;Disease;Environment;Extracellular Matrix;Face;Fracture;fracture risk;Gene Expression Profile;Genetic Diseases;Goals;Heterogeneity;Human;Impaired healing;improved;in vivo;Injury;insight;intravital imaging;KDR gene;Label;Ligands;Location;long bone;Maintenance;Mastication;Methods;Modeling;Modification;Molecular;mouse model;Mus;Mutation;Natural regeneration;neutralizing antibody;novel;Oral;Osteoblasts;Osteogenesis Imperfecta;Patients;Periosteal Cell;Periosteum;Population;postnatal;Procollagen;Proliferating;RANTES;receptor;Regulation;Reporter;restoration;selective expression;Series;Severities;Signal Transduction;single cell analysis;single-cell RNA sequencing;Site;skeletal disorder;skeletal stem cell;Source;stem cell biomarkers;stem cell function;stem cell migration;stem cell model;stem cell proliferation;stem cells;success;Surface;Tail;Technology;Testing;Transforming Growth Factor beta;Transplantation;Vascular Endothelial Growth Factors;Wild Type Mouse;Work

PROJECT_TITLE: Regulation of Skeletal progenitor cells in Osteogenesis Imperfecta

STUDY_SECTION: SBDD

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


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Title: Cellular and Metabolic Basis of the Role of CYP1B1 in Liver Fibrosis Project Narrative Activation of hepatic stellate cells (HSCs) is central to the pathogenesis of liver fibrosis. The cytochrome P450 1B1 (CYP1B1) was initially recognized as a xenobiotic enzyme that metabolizes xenobiotics. CYP1B1 is better known for its extrahepatic functions, whereas the role of CYP1B1 in the liver fibrosis has not been reported. The goal of this study is to test our hypothesis that CYP1B1 has a cell-type specific role in liver fibrosis. We hypothesize that CYP1B1 has a cell-type specific role in HSC activation and liver fibrosis. Specifically, we hypothesize that HSC and/or HEP ablation or pharmacological inhibition of Cyp1b1 inhibits HSC activation and liver fibrosis. Mechanistically, inhibition of Cyp1b1 attenuates HSC activation by suppressing the intestinal trehalase, leading to the accumulation of trehalose, a non-reducing disaccharide that inhibits HSC activation and liver fibrosis. Our study will uncover a previously unrecognized endobiotic function of CYP1B1 in liver fibrosis mediated by the liver-intestine organ crosstalk and the trehalose metabolite. Pharmacological inhibition of Cyp1b1 and/or the use of trehalose represent novel strategies for the clinical management of liver fibrosis.

PI_NAMEs: XIE, WEN  (contact)

PROGRAM_OFFICER_NAME: DOO, EDWARD

PROJECT_TERMS: Ablation;antifibrotic treatment;Aromatic Polycyclic Hydrocarbons;Attenuated;Autophagocytosis;bile duct;Cell Separation;cell type;chronic liver injury;Clinical Management;Cytochrome P450;Data;Disaccharides;Enzymes;Estrogens;Extracellular Matrix Proteins;Extrahepatic;FDA approved;Fibrosis;Genes;Genetic Transcription;Goals;Heme;Hepatic;Hepatic Stellate Cell;Hepatocyte;Human;in vivo;inhibitor;Intestines;Knock-out;Knockout Mice;Ligation;Liver;Liver Cirrhosis;Liver Failure;Liver Fibrosis;Mediating;Metabolic;metabolomics;Mixed Function Oxygenases;Molecular;Molecular Biology;Mus;Myofibroblast;NADP;nonalcoholic steatohepatitis;novel;novel strategies;Organ;Pathogenesis;Pharmaceutical Preparations;pharmacologic;Portal Hypertension;prevent;Prevention;Primary carcinoma of the liver cells;Production;promoter;Reporting;Retinoids;Role;Testing;Testosterone;Thioacetamide;Trehalase;Trehalose;Wilms Tumor Genes;WT1 gene;Xenobiotics

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

PHR: Project Narrative Cochlear implants (CIs) allow most users to hear and understand speech in quiet environments but, they are less effective in the presence of background noise and also do not provide good appreciation of music. An important contributor to suboptimal performance is the imprecise nature of electrode-based stimulation, leading to activation of broad regions of the target auditory neurons; such broad activation leads to unwanted interactions among neighboring channels that degrade the frequency information transmitted to the brain. Our recent findings show that magnetic stimulation from micro-coils activates narrow regions of the target auditory neurons compared with current (electrode) technology, thereby better approximating the neural signaling patterns that arise naturally; we propose here to more fully evaluate the potential of micro-coils as a next-generation CI.

PI_NAMEs: ARENBERG, JULIE G;FRIED, SHELLEY  (contact)

PROGRAM_OFFICER_NAME: MILLER, ROGER

PROJECT_TITLE: Development of a Micro-coil Based Cochlear Implant

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-ICN-W(02)M]


NIH_SPENDING_CATS: Bioengineering;Dental, Oral, and Craniofacial Disease;Osteoporosis;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: Craniofacial bone loss in children occurs frequently due to trauma or congenital bone loss for which costly and invasive surgeries are the only remedy. Autologous bone grafting is the only approved surgical approach to repair craniofacial bone in children but involves high cost, morbidity, and revision surgeries. There are no bone regenerative strategies for children. We will target the Jagged1 non-canonical signaling pathway to develop a novel regenerative strategy to correct craniofacial bone loss using pre-clinical animal models as the first step towards developing a bone regenerative strategy for pediatric patients.

PI_NAMEs: GOUDY, STEVEN L (contact)

PROJECT_TERMS: Adult;Alagille Syndrome;Animal Model;Animals;arm;Autologous;Biliary;Binding;biomechanical test;BMP2 gene;bone;bone cell;Bone Development;Bone Injury;bone loss;Bone Marrow;Bone Regeneration;bone repair;Bone Tissue;Bone Transplantation;Calvaria;carcinogenicity;Cardiac;Cell Density;Cells;Cephalic;Child;Childhood;Clinical;clinically relevant;Complex;cost;craniofacial;craniofacial bone;craniofacial repair;craniofacial structure;craniofacial tissue;Cues;cytokine;Data;Defect;Engineering;Ethylenes;Future;Genes;Glycols;Goals;Harvest;Hip Fractures;Hip Pain;Hip region structure;Histology;Hospitals;Human;Hydrogels;Immune;In Vitro;in vivo;in vivo evaluation;Inflammation;innovation;Life;Ligands;long bone;Maleimides;Measures;Mediating;Mesenchymal Stem Cells;mineralization;Modeling;Morbidity - disease rate;mouse model;Mus;Mutation;Neural Crest;notch protein;Notch Signaling Pathway;novel;Operative Surgical Procedures;Organ Transplantation;Oryctolagus cuniculus;Osteoblasts;Osteogenesis;osteogenic;Outcome;Pathway interactions;Patients;pediatric patients;Phenocopy;Phenotype;Physiologic Ossification;pre-clinical;Pre-Clinical Model;preclinical study;progenitor;Proteomics;Publishing;receptor;regenerative;regenerative approach;regenerative therapy;Reporting;Research;Risk;Role;Safety;Second Look Surgery;Signal Pathway;Signal Transduction;Spine surgery;stem cells;System;targeted treatment;Testing;therapy development;Time;Tissue Engineering;tissue reconstruction;tissue regeneration;Tissues;transcriptome sequencing;translational impact;Trauma;Work

PROJECT_TITLE: Jagged1-based craniofacial bone regeneration

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Neurosciences;Rare Diseases;Tuberculosis

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: The proposed research has public health relevance because it will determine the etiology, role of co-infections, and new molecular diagnostic targets in HIV-associated meningitis in order to improve patient outcomes.

PI_NAMEs: SIDDIQI, OMAR KHALIK (contact)

PROGRAM_OFFICER_NAME: SRINIVASAN, SUDHA

PROJECT_TERMS: Address;Adult;Africa South of the Sahara;African;Area;Automobile Driving;Autopsy;Biological Assay;Biological Markers;Biopsy Specimen;Brain;brain tissue;Burial;Caring;Central Nervous System;Central Nervous System Infections;Cerebrospinal Fluid;Cessation of life;Clinical;Clinical Management;co-infection;Collection;comorbidity;Core Biopsy;Country;Death Rate;Diagnosis;Diagnostic;diagnostic biomarker;diagnostic strategy;doctoral student;Etiology;Evaluation;Family;Fellowship;Future;Goals;Histologic;Histology;HIV;HIV diagnosis;HIV Seropositivity;Hour;improved;improved outcome;Incidence;Infection;innovation;Inpatients;insight;Investigation;Knowledge;Laboratories;lateral flow assay;lipidomics;Lipids;lipoarabinomannan;low and middle-income countries;Measures;Meningeal Tuberculosis;Meningitis;Metagenomics;Methods;Microbiology;minimally invasive;Molecular;molecular diagnostics;mortality;Mycobacterium tuberculosis;mycobactins;neuropathology;next generation sequencing;Organ;Organism;Outcome;pathogen;Pathologist;Pathology;Patient-Focused Outcomes;Patients;point of care;point-of-care diagnostics;Polymerase Chain Reaction;Population;portability;Preparation;Prevalence;prevent;programs;public health relevance;Rapid diagnostics;Recommendation;Religious Belief;Research;Resource-limited setting;Role;Sampling;screening;Services;Site;Specificity;Spinal Puncture;Symptoms;Taboo;Testing;Tissue Sample;Tissues;Training;treatment strategy;uptake;Zambia

PROJECT_TITLE: Minimally Invasive Tissues Sampling to Evaluate HIV-associated Meningitis in Zambia


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Nutrition;Parkinson's Disease;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: J. DAVID GLADSTONE INSTITUTES

PHR: PROJECT NARRATIVE Neurodegenerative dementias including Alzheimer’s disease afflict many elderly people in our society, and effective treatments to prevent neuronal death are severely lacking. Metabolic stress and endosomal dysfunction are early features of neurodegenerative disease, but how these cause neuron death, and strategies to maintain neuron resilience, remain elusive. This proposal will significantly advance our understanding of how endosome- associated risk genes for Alzheimer’s and Parkinson’s disease contribute to metabolic vulnerability and proteostatic functional decline in human neurons, and will explore genetic and metabolic restorative approaches.

PI_NAMEs: BENNETT, NEAL  (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Address;alpha synuclein;Alzheimer's Disease;Alzheimer's disease risk;Amyloid beta-Protein;apolipoprotein E-3;apolipoprotein E-4;Biological;career development;causal variant;Cell Death;cell growth regulation;Cell Line;Cell Physiology;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Communication;Communities;CRISPR interference;Data;Defect;Dementia;Dementia with Lewy Bodies;Development;Development Plans;Diabetes Mellitus;disorder risk;effective therapy;Elderly;Endosomes;Energy consumption;Energy Metabolism;experience;Experimental Designs;Exposure to;Failure;Foundations;functional decline;Functional disorder;gene interaction;gene therapy;Genes;Genetic;genetic manipulation;Genetic Predisposition to Disease;genetic risk factor;Genotype;Glucose;glucose metabolism;Glycolysis;Goals;Human;human induced pluripotent stem cells;Impaired cognition;Impairment;improved;Individual;Induced pluripotent stem cell derived human neuron;insight;knock-down;Knowledge;Lead;Lipids;Measures;Mentorship;Metabolic;metabolic abnormality assessment;Metabolic dysfunction;Metabolic Pathway;Metabolic stress;Metabolism;metabolomics;Mutation;Nerve Degeneration;neurodegenerative dementia;Neurodegenerative Disorders;neuron loss;neuronal cell body;Neuronal Differentiation;neuronal survival;Neurons;novel;Parkinson Disease;Pathology;Pathway interactions;Persons;Predisposition;preservation;prevent;programs;Property;protein transport;Proteins;proteostasis;Radiolabeled;Recycling;Research;research and development;Research Personnel;resilience;Respiration;response;Risk Factors;risk variant;screening;sensor;skills;Societies;Stress;Substrate Interaction;Supplementation;Synapses;System;tau Proteins;Techniques;Technology;Testing;Therapeutic;Therapeutic Intervention;Training;transcriptomics;Ubiquitin;Variant;whole genome

PROJECT_TITLE: Metabolic Vulnerability and Effects of APOE in Human Neurons with Impaired Endocytic Recycling

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Congenital Structural Anomalies;Pediatric;Precision Medicine;Rare Diseases

ORG_CITY: Chicago

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Project narrative The extracellular matrix (ECM) is a complex assembly of hundreds of proteins and a critical regulator of cell, tissue, and organ functions. Yet, the ECM is understudied. Here, we propose to leverage the resources generated by the HuBMAP consortium to build and deploy spatially-resolved maps of the ECM of each tissue of the human body, a first step toward understanding ECM functions in health and disease.

PI_NAMEs: GAO, YU ;NABA, ALEXANDRA  (contact)

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: 3-Dimensional;Aging;Antigens;Atlases;Basement membrane;Binding;Binding Proteins;Biochemical;Biology;Biomedical Research;Cardiovascular Diseases;Cell Physiology;Cell Surface Receptors;cell type;Cells;cellular transduction;Collaborations;Collagen;Communities;Complex;Computational Biology;Computer Models;computerized data processing;Data;data analysis pipeline;Data Collection;Data Set;Databases;Degenerative polyarthritis;Development;Diagnostic;Disease;ECM receptor;Effectiveness;Ehlers-Danlos Syndrome;Enhance LC;Ensure;Etiology;Extracellular Matrix;Extracellular Matrix Proteins;Extracellular Space;Fibrosis;Future;Genes;Goals;Growth Factor;Health;Hereditary nephritis;Human;Human BioMolecular Atlas Program;human tissue;Image;intercellular connection;interstitial;Knowledge;Level of Evidence;Link;Malignant Neoplasms;Maps;Marfan Syndrome;Mass Spectrum Analysis;member;Methods;migration;Modality;Modeling;Morphogenesis;Musculoskeletal Diseases;Myopathy;Organ;Pathway interactions;Physiology;Population;Post-Translational Protein Processing;Preparation;Process;Production;Proliferating;protein expression;Proteins;proteogenomics;Proteoglycan;Proteome;Proteomics;Protocols documentation;Receptor Gene;Resolution;Resources;RNA;Role;Sampling;scaffold;Set protein;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Technology;technology development;Therapeutic;Thinking;Time;tissue mapping;Tissues;Transcript;transcriptomics;Visualization

PROJECT_TITLE: Thinking outside the cell: Leveraging HuBMAP data to build the human ECM atlas


NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Immunotherapy;Women's Health Research

ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: Project Narrative In this proposal, we will employ complementary molecular, cellular, genetics, and state-of-the-arts next-generation sequencing techniques, as well as various mouse models, to investigate the function of RBMS3/PRRX1 axis in regulating immunosuppressive effect and response to immunotherapy for TNBC. The results of this study will not only provide insight into the mechanism of TNBC progression, but also lay the foundation for establishing the RBMS3/PRRX1 axis as a therapeutic target for TNBC treatment.

PI_NAMEs: GIBSON, HEATHER MARIE;WU, GUOJUN  (contact)

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: Address;Animal Model;anti-CTLA4;anti-PD-1;Automobile Driving;Biological Assay;Bone Marrow;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Model;Breast Cancer Patient;breast cancer progression;Breast Cancer therapy;Breast Cancer Treatment;Breast Epithelial Cells;C57BL/6 Mouse;cancer cell;cancer type;Carcinoma;cell motility;Cells;chemokine;Chemotaxis;Coculture Techniques;Complex;Contralateral;cytokine;Development;Developmental Process;Disease;effective therapy;epithelial to mesenchymal transition;exhaustion;Expression Profiling;Flow Cytometry;Foundations;Gene Targeting;Genes;Genetic;Genetic Transcription;Goals;Homeobox;Human;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immunocompetent;Immunologic Memory;immunological status;immunosuppressed;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Implant;improved;In Vitro;in vivo;Inbred BALB C Mice;Infiltration;Inflammation;Inflammatory;insight;Intervention;knock-down;Life;Link;Literature;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;MDA MB 231;Mediating;Mesenchymal;Metastatic breast cancer;Modeling;Molecular;Monitor;mortality;Motility;mouse model;Mus;Neoplasm Metastasis;next generation sequencing;Outcome;overexpression;Pathologic Processes;Peripheral;Phenotype;Population;Primary Neoplasm;Prognosis;programs;Property;Proteins;recruit;Reproducibility;Research;response;RNA analysis;RNA Binding;Role;Sampling;Solid;Techniques;Testing;Therapeutic Intervention;therapeutic target;tissue repair;transcriptome sequencing;transcriptomics;Translating;treatment response;triple-negative invasive breast carcinoma;tumor;tumor growth;Tumor Immunity;tumor microenvironment;tumor progression;tumor-immune system interactions;tumorigenesis

PROJECT_TITLE: Exploration of the immunosuppressive function of RBMS3/PRRX1 axis in TNBC


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

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE: Biliary atresia (BA) is a cholestatic liver disease of infancy that is the leading cause of pediatric liver transplantation. Evidence suggests a role for macrophages in the pathogenesis of BA, however, the specific immune-metabolic networks regulating the macrophage immune response have not been well defined. We aim to define how serum metabolites and the hepatic macrophage transcriptional phenotype at diagnosis may influence patient outcome to ultimately identify novel immune-modulatory treatment strategies.

PI_NAMEs: TAYLOR, SARAH ANN (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: 2 year old;Anti-Inflammatory Agents;Apoptotic;Area;Arginine;ATAC-seq;Bile fluid;Biliary;Biliary Atresia;Biochemical Pathway;Biology;cell dedifferentiation;Cells;Characteristics;Childhood;Cholestasis;Clinical;cohort;Collaborations;Critical Pathways;Data;Diagnosis;differential expression;Disease;Drainage procedure;Early identification;Epigenetic Process;epigenetic regulation;Foundations;Freezing;Future;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic Transcription;Granulocyte-Macrophage Colony-Stimulating Factor;Hepatic;Hepatocyte;Human;hydrophilicity;Immune;Immune response;immunoregulation;infancy;Infant;Inflammatory;innovation;Liver;liver transplantation;Macrophage;Measures;Medical;Mentors;Metabolic;Metabolism;metabolomics;Modification;monocyte;Mus;Nature;new therapeutic target;Nitric Oxide Synthase;novel;Obstruction;Operative Surgical Procedures;Outcome;Pathogenesis;Pathway interactions;Patient-Focused Outcomes;Patients;Phenotype;Polyamines;Predictive Value;prognostic;Prognostic Marker;programs;Putrescine;recruit;Regulation;Research;Research Personnel;Rheumatology;ROC Curve;Role;Running;Sampling;Serum;single nucleus RNA-sequencing;Spermidine;Spermine;survival prediction;Survival Rate;Time;total measurement Bilirubin;transcriptional reprogramming;Transplantation;treatment strategy;Up-Regulation;uptake;Validation

PROJECT_TITLE: Immune-Metabolic Regulation of Biliary Atresia

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


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

ORG_DEPT: NEUROLOGY

ORG_STATE: CA

PHR: Intercellular transmission and subsequent amplification of pathological tau contributes significantly to the progression of Alzheimer’s disease (AD) and other tauopathies, the underlying mechanisms of which remains largely unknown. Our preliminary data demonstrates for the first time that soluble tau post-translational modifications (PTMs) could dramatically affect the amplification of pathological tau in AD and other tauopathies, which represents a novel mechanism for the modulation of pathological tau spreading. In this proposed study, we will systematically explore how soluble tau PTMs would regulate the amplification of pathological tau in AD and other tauopathies.

PI_NAMEs: PENG, CHAO  (contact)

PROGRAM_OFFICER_NAME: MCGAVERN, LINDA

PROJECT_TERMS: Acetylation;Acetyltransferase;Affect;alpha synuclein;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Alzheimer's disease therapy;Astrocytes;Brain;brain cell;brain control;Brain region;cell type;Cells;corticobasal degeneration;Data;Development;Disease Progression;disorder subtype;Environment;Enzymes;in vivo;insight;Knockout Mice;mimetics;Molecular;Mus;mutant;Neuroglia;Neurons;new therapeutic target;novel;Oligodendroglia;Pathologic;Performance;Phosphorylation;Phosphotransferases;Pick Disease of the Brain;Post-Translational Protein Processing;Progressive Supranuclear Palsy;Property;Proteins;Regulation;Reporting;response;Site;tau conformation;tau mutation;tau Proteins;tau-1;Tauopathies;Testing;Therapeutic;Time;transmission blocking;transmission process

PROJECT_TITLE: Regulation of Pathological Tau Transmission by Soluble Tau Post-Translational Modifications

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Genetics;Multiple Sclerosis;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: IRVINE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Narrative: An important unmet clinical need for MS patients is an effective method for promoting remyelination that can ameliorate clinical symptoms associated with demyelination and restore motor function while limiting immune cell infiltration into the CNS. Using a well-accepted preclinical animal model for MS, key areas of research include identifying signaling pathways governing neuroinflammation, characterizing signaling pathways controlling oligodendroglia maturation and remyelination, and refinement of strategies to improve neural progenitor cell (NPC)-mediated remyelination following surgical engraftment into the CNS and how non-coding RNAs influence disease. In addition, we will employ state- of-the-art single cell and nuclear RNA sequencing to better understand how immune cells interact with resident cells of the CNS during demyelination and remyelination.

PI_NAMEs: LANE, THOMAS E (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Ablation;Animal Model;Area;associated symptom;Axon;axon injury;C57BL/6 Mouse;Cell Communication;Cell Culture Techniques;Cell Maturation;Cells;chemokine;Clinical;CRISPR/Cas technology;Demyelinating Diseases;Demyelinations;Disease;Disease Progression;Engraftment;Event;Generations;Genes;genetic approach;Goals;Human;Immune;immune cell infiltrate;improved;Infection;insight;Laboratories;Mediating;Methods;MHV-JHM;Microglia;Modeling;Molecular;Motor;Multiple Sclerosis;multiple sclerosis patient;Murine hepatitis virus;Mus;nerve stem cell;neuroinflammation;new therapeutic target;Nuclear RNA;oligodendrocyte progenitor;Oligodendroglia;Operative Surgical Procedures;Pathogenesis;Patients;pre-clinical;Predisposition;Procedures;remyelination;repaired;Research;Research Proposals;Severities;Signal Pathway;Signal Transduction;Therapeutic Intervention;transcriptome sequencing;two photon microscopy;Untranslated RNA;Viral;virus-induced demyelination;Visualization

PROJECT_TITLE: Defining mechanisms of disease and repair in a viral model of multiple sclerosis