NIH_SPENDING_CATS: Diabetes;Regenerative Medicine

ORG_CITY: NEW YORK

ORG_STATE: NY

PHR: Narrative Types 1 and 2 diabetes represent a global health crisis, and result in part or entirely from a reduction of insulin- producing pancreatic beta cells. Despite the existence of ~30 different commercially available diabetes drugs, none has the ability to induce human beta cell regeneration. We describe herein entirely novel and tractable pathways to human beta cell proliferation, and have identified multiple combinations of drugs that act via these pathways to induce human beta cells to regenerate.

PI_NAMEs: STEWART, ANDREW F. (contact);WANG, PENG

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Adult;Affect;Agonist;American;analog;Beta Cell;c-myc Genes;Calcium;Calcium Channel;CCNE1 gene;CDC2 gene;CDKN1A gene;CDKN1C gene;Cell Count;Cell Cycle;Cell Cycle Regulation;Cell Differentiation process;Cell Nucleus;Cell Proliferation;cell regeneration;Chromatin;Complex;CREBBP gene;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cyclin A;Cyclins;Cytoplasm;Diabetes Mellitus;Dimethyl Sulfoxide;Dose;drug action;Drug Combinations;Enzyme Inhibitor Drugs;Extended Family;EZH2 gene;Family;FK506;FOXM1 gene;GCG gene;gene repression;Genes;Genome;genome-wide;global health;Goals;Harmine;Human;In Vitro;in vivo;indexing;inhibitor;Insulin;Insulin-Dependent Diabetes Mellitus;insulinoma;islet;Label;Link;Maintenance;Mediating;Mediator;member;Metabolic syndrome;Modeling;Natural regeneration;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Nuclear;nuclear factors of activated T-cells;Pathway interactions;Persons;Pharmaceutical Preparations;Phosphorylation;Phosphotransferases;Polycomb;Prediabetes syndrome;Proliferating;Proteins;receptor;Refractory;regenerative therapy;Regulation;Research;Residual state;restraint;Role;Scaffolding Protein;Signal Transduction;Structure of beta Cell of islet;synergism;therapeutic target;trafficking;transcription factor;transdifferentiation;Transforming Growth Factor beta;YY1 Transcription Factor

PROJECT_TITLE: DREAM Complex Maintenance of Human Beta Cell Quiescence

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project Narrative Cancer immunosurveillance ascribes a role of cellular immunity in eliminating transformed cells. Cancer immunotherapy approaches exploiting such activity of conventional T lymphocytes have produced durable responses in a subset of cancer patients. Experiments proposed in this project will define a novel class of cancer immunosurveillance response mediated by tumor-resident cytotoxic innate lymphocytes and innate-like T cells, which can be targeted for therapy of a wide range of solid tumors.

PI_NAMEs: LI, MING  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Ablation;Acceleration;adherent junction;Agonist;Alleles;Antigens;autoreactive T cell;cancer cell;cancer immunotherapy;Cancer Patient;cancer therapy;cancer type;Carcinoma;CD8-Positive T-Lymphocytes;CDH1 gene;Cell Differentiation process;Cell Lineage;cell transformation;Cells;Cellular Immunity;Characteristics;Chromatin;cytokine;cytotoxic;cytotoxicity;Development;Diphtheria Toxin;E-Cadherin;Enterobacteria phage P1 Cre recombinase;exhaust;Exhibits;experimental study;gain of function;Gene Expression;Genetic;genomic locus;Granzyme;Growth;Hematopoietic stem cells;immune checkpoint blockade;Immune response;Immune system;Immunologic Surveillance;Immunotherapy;insight;Integrins;Interleukin-15;Intestines;intraepithelial;intravital imaging;Investigation;Life;Lymphocyte;Lymphoid Cell;Maintenance;Malignant Neoplasms;Mammary gland;Mammary Neoplasms;Maps;Mediating;Missense Mutation;Modality;mouse model;Mouse Strains;Mus;Names;Natural Killer Cells;neoplastic cell;novel;Oncogenes;Parabiosis;Pathway interactions;Patient Care;Patients;perforin;Process;programs;receptor;Receptor Signaling;Regulation;Renal Cell Carcinoma;Reporter;Repression;Residencies;response;Role;Sampling;Sentinel;Signal Transduction;Solid Neoplasm;Specific qualifier value;stem cells;T-Cell Receptor;T-Lymphocyte;targeted treatment;Testing;Thymus Gland;Tissue Expansion;Tissues;transcription factor;transcriptome;Transforming Growth Factor beta;Transgenic Mice;tumor;Tumor Escape;tumor growth;tumor progression;Tumor Promotion;Tumor Tissue

PROJECT_TITLE: Ontogeny and Function of Tumor-Resident Innate Lymphocytes and Innate-Like T Cells

STUDY_SECTION: TTT

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


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Diabetes;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Lung

ORG_CITY: CORAL GABLES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative COVID-19 is a severe threat to human health, caused by the novel coronavirus SARS-CoV-2. Infection with this virus can trigger an increase in blood glucose levels but the underlying mechanisms are not understood. We found that vascular cells in pancreatic islets, the organs that control blood glucose levels, express the receptor for the virus. Here we will study the effects of SARS-CoV-2 on islet vascular function and glucose metabolism.

PI_NAMEs: ALMACA, JOANA  (contact)

PROJECT_TERMS: 2019-nCoV;ACE2;Affect;Amino Acid Sequence;angiotensin I (1-7);Angiotensin II;Animal Model;Autopsy;Blood flow;Blood Glucose;blood glucose regulation;Blood Vessels;Cells;cellular targeting;Coronavirus;COVID-19;COVID-19 patient;Data;Diabetes Mellitus;diabetes pathogenesis;disease natural history;Endocrine;Endocytosis;Functional disorder;Functional impairment;global health;Glucose Intolerance;glucose metabolism;Hamsters;Health;Healthcare;histopathological examination;Hormone secretion;Human;Hypoxia;Immunohistochemistry;Impairment;in vivo;Incubated;Infection;Infiltration;Inflammation;Injections;islet;Islets of Langerhans;Lesion;Link;Lung;Microvascular Dysfunction;Modeling;mortality;non-diabetic;novel;novel coronavirus;Organ;Pancreas;Pancreatic Diseases;Pancreatitis;particle;Patients;Pattern;Pericytes;permissiveness;Persons;Phenotype;Predisposition;Property;Proteins;Publishing;receptor;Recombinant Proteins;Recombinants;Research;Respiratory Failure;response;SARS-CoV-2 infection;SARS-CoV-2 spike protein;Slice;small molecule inhibitor;spatiotemporal;Specimen;Surface;Testing;Time;Tissues;Tropism;Vascular System;Vascularization;vasoconstriction;Vasodilator Agents;vasomotion;Viral;Virus;Virus Diseases;Virus Receptors

PROJECT_TITLE: Investigating the link between pericyte dysfunction and loss of glucose homeostasis in COVID-19

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Dental, Oral, and Craniofacial Disease;Neurosciences;Nutrition

ORG_CITY: WALTHAM

ORG_DEPT: PSYCHOLOGY

ORG_NAME: BRANDEIS UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative When a taste is placed on our tongues, we must recognize that a taste is on the tongue, identify that taste, decide whether it’s palatable or not, and then either swallow it or expel it. This thought process can be observed to play out in the firing of neurons in taste cortex, but evidence suggests that cortex doesn’t work alone. We will rigorously test how the amygdala (the seat of emotion in the brain) and hypothalamus (the center that controls hunger and thirst) work with cortex, and with one another, to make taste decisions happen, and how these decisions get implemented by motor circuits—adding to a systemic understanding of taste that will help us fight against a spectrum of feeding-related disorders.

PI_NAMEs: KATZ, DONALD B (contact)

PROGRAM_OFFICER_NAME: SABRI, MERAV

PROJECT_TERMS: Affect;Amygdaloid structure;Automobile Driving;awake;Axon;Back;Behavior;Biological;Brain;brain circuitry;Brain region;Brain Stem;cell type;Cells;central pattern generator;Code;Complex;Consumption;Coupled;Coupling;Decision Making;Deglutition;Disease;Dissociation;Eating;Electrophysiology (science);Emotions;experimental study;feeding;fighting;Food;Generations;Green Fluorescent Proteins;Hunger;Hypothalamic structure;insight;Lateral;Lighting;Mediating;Molecular;Monitor;Motor;Movement;Nature;neural;Neurons;Nonlinear Dynamics;novel;Optics;optogenetics;Oral;Oral cavity;orofacial;Output;Pathway interactions;Perception;Periodicity;Play;Population Dynamics;Process;Production;Property;Prosencephalon;Rattus;Reporting;Research Project Grants;response;Rodent;Role;Sampling;sensorimotor system;Signal Transduction;Site;Stimulus;Structure;sugar;sweet taste perception;System;Taste Perception;taste system;Testing;Thinking;Thirst;Time;Tongue;tool;Work

PROJECT_TITLE: Temporal Coding and Palatability in Gustatory Cortex


ADMINISTERING_IC: AG

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Machine Learning and Artificial Intelligence;Neurodegenerative;Patient Safety

ORG_DEPT: PHYSIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Swallowing dysfunction is common in older adults, and leads to significant morbidity, including aspiration pneumonia, malnutrition, and dehydration, and is the leading cause of death in older adults with AD/ADRD. Unfortunately, the bedside swallow evaluation currently used by speech language pathologists and nurses to detect swallowing dysfunction is unreliable, especially in individuals with AD/ADRD. We propose to develop a sensitive smartphone-based clinical decision support tool that incorporates analysis of multiple characteristics of a patient's recorded voice and cough to determine their aspiration risk.

PI_NAMEs: RAMEAU, ANAIS  (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Acoustics;Address;Adult;Advocacy;Affect;Aging;Alzheimer's disease related dementia;aspirate;Aspiration Pneumonia;Barium swallow;Behavioral Research;Biological Markers;canine model;career;career development;Caring;Cause of Death;Cellular Phone;Characteristics;Clinical;clinical decision support;cohort;Collaborations;cost;Coughing;curriculum development;Data;Deglutition;Deglutition Disorders;Dehydration;Dental Hygiene;Detection;dietary;digital;Elderly;Environment;Evaluation;Evidence based treatment;Exercise;experience;Fellowship;flexibility;Food;Foundations;frailty;Functional disorder;Funding;Geriatrics;Goals;Grant;Head and Neck Surgery;Health Care Costs;high risk;Human;human old age (65+);improved;improved outcome;Individual;Institution;interdisciplinary collaboration;interest;Language;Leadership;Length of Stay;Lung;Machine Learning;Malnutrition;medical schools;Mentors;Mentorship;Methods;mobile application;Morbidity - disease rate;mortality risk;novel strategies;Nurses;Nursing Assessment;Nursing Homes;older adult;Oral;Otolaryngologist;Otolaryngology;Pathologist;Patients;Perception;Performance;Pharyngeal structure;Pilot Projects;prospective;Protocols documentation;Research;Research Personnel;Risk;Site;skills;smartphone application;sound;Specialist;Speech;Standardization;support tools;Techniques;Technology;Testing;tool;treatment strategy;United States National Institutes of Health;Vision;vocal cord;Voice

PROJECT_TITLE: Developing an App-Based Voice Clinical Decision Support Tool to Augment the Sensitivity of the Bedside Swallow Evaluation in Older Adults


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Emerging Infectious Diseases;Immunotherapy;Infectious Diseases;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: HERSHEY

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: PROJECT NARRATIVE JC polyomavirus (JCPyV), a prevalent human-only pathogen, causes life-threatening brain diseases in immunologically compromised individuals. The list of immunotherapeutic and chemotherapeutic agents linked to JCPyV CNS diseases is rapidly expanding; no anti-JCPyV agents are available. Using a mouse virus in the same family as JCPyV, we developed a tractable animal model to explore early stages in the pathogenesis of polyomavirus brain infections that precede development of irreversible lesions.

PI_NAMEs: LUKACHER, ARON ELIOT (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Affinity;Animal Model;Autoimmune;Biological Products;Brain;Brain Diseases;brain parenchyma;Capsid Proteins;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Central Nervous System Diseases;Central Nervous System Infections;Cerebrum;chemotherapeutic agent;chronic infection;Complication;Cryoelectron Microscopy;Custom;Demyelinations;Development;Disease;drug withdrawal;Ependyma;Epitopes;Event;Family;Foundations;Hematologic Neoplasms;Heterogeneity;Human;human pathogen;image reconstruction;Immune;immune modulating agents;Immunity;Immunologics;Immunotherapeutic agent;in vivo;in vivo evaluation;Incidence;Individual;Infection;Inflammatory;interleukin-21;Invaded;JC Virus;Lesion;Life;Link;Maintenance;Maps;Memory;Modeling;mortality;mouse polyomavirus;multiple sclerosis patient;Mus;Mutation;natalizumab;Natural Immunity;neuropathology;neutralizing antibody;next generation sequencing;pathogen;Pathogenesis;Patients;Polyomavirus;preservation;Progressive Multifocal Leukoencephalopathy;Reaction;Relapse;Resolution;Staging;STAT1 gene;T cell response;T-Lymphocyte;Therapeutic;Three-Dimensional Imaging;tissue culture;Tropism;Tysabri;Variant;Ventricular;Virus;Visualization

PROJECT_TITLE: Deciphering Early Stages of Polyomavirus CNS Pathogenesis and Immunity


ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Mental Health;Mental Illness;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE PTSD prevalence is high and PTSD increases the risk of dementia. The proposed research will: a) investigate the impact of PTSD on the rate of domain-specific cognitive decline, b) test potential effect modifiers, including sex, of the relationship between PTSD and rate of cognitive decline, and c) determine the association between cognitive functioning and PTSD severity with and without Criterion A trauma. Successful completion of this project has important public health implications including indicating whether PTSD should be considered a target for the early prevention of cognitive decline that may lead to dementia and increasing understanding of sex differences in the relationship between PTSD and cognitive decline.

PI_NAMEs: LAWRENCE, KAREN ANN (contact)

PROGRAM_OFFICER_NAME: TREVINO, MELISSA

PROJECT_TERMS: Accidents;Address;Adult;Affect;aged;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Anxiety;apolipoprotein E-4;biopsychosocial factor;carrier status;Clinical;clinical center;Clinical Sciences;Cognition;Cognitive;Cognitive aging;cognitive function;cohort;comorbidity;COVID-19;COVID-19 pandemic;Cross-Sectional Studies;Data;Data Collection;Dementia;dementia risk;Diagnosis;Diagnostic;Diagnostic and Statistical Manual of Mental Disorders;disability;Disasters;DSM-V;Epidemiology;Episodic memory;Event;executive function;first responder;functional decline;Funding;Goals;Health;human old age (65+);Impaired cognition;Incidence;Intervention;Investigation;Kentucky;Link;Longitudinal Studies;Medical;meetings;men;Mental Depression;Mentored Research Scientist Development Award;Mentors;Mentorship;mild cognitive impairment;military veteran;Modeling;Modification;multilevel analysis;National Center for Advancing Translational Sciences;Neuropsychology;older adult;pandemic disease;Participant;Pharmaceutical Preparations;post-pandemic;Post-Traumatic Stress Disorders;pre-clinical;pre-pandemic;Prevalence;Prevention;processing speed;prospective;Psychologist;Public Health;Recording of previous events;recruit;Research;Research Design;Research Personnel;Risk;Risk Factors;Severities;sex;Sex Differences;sexual assault;Short-Term Memory;statistics;Survivors;Symptoms;Testing;Training;Translational Research;Trauma;Traumatic Brain Injury;traumatic stress;United States;Universities;War;Woman;Women's prevalence;young adult

PROJECT_TITLE: Cognitive Aging Trajectories in Survivors of Trauma

STUDY_SECTION: AGCD

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


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Burden of Illness;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: STANFORD

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE – RELEVANCE While a growing body of evidence demonstrates the presence of racial bias in algorithms, little is known about how racial bias in algorithms impacts disparities in public health insurance programs, such as Medicaid and Medicare. The central objectives of this project are to: (i) obtain causal estimates of the effect of risk-adjusted managed long-term care (MLTC) on different care utilization and health outcomes among dual-eligible beneficiaries in New York, separately by patient race/ethnicity; (ii) identify differences in the magnitudes of racially disparate impacts across other patient characteristics, including sex, age, health status, and local area; and (iii) identify differences in the magnitudes of racially disparate impacts across different types of plans. This research will help policymakers, healthcare organizations, providers, and patients understand how bias in risk- adjusted MLTC impacts patient health, identify the subgroups of patients most severely impacted, and learn about the plan features that contribute to curbing or eliminating racial health disparities in managed care.

PI_NAMEs: LEE, AJIN ;ROSSIN-SLATER, MAYA  (contact)

PROGRAM_OFFICER_NAME: NOVAK, PRISCILLA JOY

PROJECT_TERMS: Acute;Affect;Age;Algorithms;Area;Authorization documentation;Automobile Driving;Behavior;beneficiary;black patient;Black race;care systems;Caring;Characteristics;Chronic;Classification;Code;comorbidity;Contracts;cost;County;Cream;Data;Data Set;design;Disparity;Drug Prescriptions;Drug usage;dual eligible;Enrollment;Ethnic Origin;Ethnic Population;Exclusion;financial incentive;Gender;Government;Health;Health Care Costs;health care disparity;health care service;health care service organization;health care service utilization;Health Insurance;Health Status;Healthcare;hospitalization rates;Incentives;Income;Inpatients;Insurance Carriers;insurance plan;Knowledge;Lead;Learning;Link;Literature;Long-Term Care;Managed Care;Managed Care Programs;Mediation;Medicare/Medicaid;Modeling;mortality;New York;Nursing Homes;Outcome;outcome disparities;participant enrollment;Patient Care;patient home care;patient subsets;Patient-Focused Outcomes;Patients;payment;Policy Maker;Privatization;programs;Provider;public health insurance;Quality of Care;Race;racial bias;racial difference;racial disparity;racial health disparity;racial population;Randomized;Records;Research;Resources;Risk Adjustment;Role;Service provision;sex;Socioeconomic Factors;Subgroup;System;Systematic Bias;Testing

PROJECT_TITLE: Racial Bias in Risk Adjustment Algorithms and Implications for Racial Health Disparities: Evidence from Dual-Eligible Medicare/Medicaid Long-term Care Patients in New York


ADMINISTERING_IC: GM

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: SEATTLE

ORG_NAME: LAMPROGEN, INC.

ORG_STATE: WA

PHR: Project Narrative There is a growing demand in clinical and personalized medicine to measure many DNA sequences in a single sample. PCR-based diagnostic assays are widely used clinically for monitoring gene expression and detecting disease-related mutations and infectious agents due to their accuracy, simplicity, and fast turnaround time, but are only able to assess 4–6 DNA sequences per sample. This project is relevant to public heath because it will significantly increase PCR multiplexing to enable clinical assays (up to 30 sequences per reaction and hundreds per instrument run), providing highly sensitive, accurate, and reproducible clinical assay measurements while eliminating the need for complex, slow, and expensive genomic sequencing.

PI_NAMEs: YU, JIANGBO  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Achievement;Address;Base Sequence;Bioinformatics;Biological Assay;carrier testing;Clinical;clinical diagnosis;clinical diagnostics;Clinical Medicine;Color;companion diagnostics;comparative;Compensation;Complex;Computer software;cost;Custom;design;Development;Diagnostic;diagnostic assay;digital;dimer;Disease;disease diagnosis;DNA Sequence;Dyes;Early Diagnosis;Energy Transfer;Exhibits;Family;Flow Cytometry;Fluorescence;Fluorescent Dyes;Fluorescent Probes;Future;Gene Expression Profiling;Genes;Genetic;Genomics;Genotype;Hemorrhage;Hydrophobicity;improved;Infectious Agent;innovation;instrument;Licensing;liquid biopsy;Measurement;Measures;method development;Methods;molecular diagnostics;Mutation;Nature;next generation sequencing;novel strategies;nucleic acid quantitation;Oligonucleotides;operation;Outcome;Penetration;Performance;personalized medicine;Pharmacotherapy;Play;point of care;Polymers;Prognosis;prognostic;Proteins;Protocols documentation;Public Health;Quantum Dots;Reaction;Reproducibility;reproductive;Risk;Role;Running;Sampling;Science;screening;Screening for cancer;Series;System;Technology;Time;Tube;Validation;Western Blotting

PROJECT_TITLE: Significant expansion of spectral multiplexing in PCR


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Primary Health Care;Rural Health;Social Determinants of Health

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Older adults make up a growing portion of rural communities in the United States, but are experiencing a two- pronged challenge of an increasingly severe burden of chronic conditions and limited access to health care— both of which have the potential to exacerbate existing rural-urban health disparities. The goal of this proposal is to measure trends in access to care, chronic condition management, and rural-urban disparities in these outcomes among older adults in the United States, and measure the effects of a novel strategy designed to bolster rural health care delivery, known as global budgets, on these outcomes using a mixed methods approach.

PI_NAMEs: CHATTERJEE, PAULA  (contact)

PROJECT_TERMS: Acceleration;Address;Adopted;Adult;Affect;Affordable Care Act;Aging;Ambulatory Care;Budgets;care delivery;career development;Caring;Chronic;Communities;Continuity of Patient Care;Country;Data;Death Rate;Dedications;design;Development Plans;Diagnosis;Disparity;econometrics;Environment;Evaluation;experience;Future;Goals;Growth;Health;Health and Retirement Study;health care availability;health care delivery;health disparity;health related quality of life;Health Services;Health Services Accessibility;Health Services Research;Healthcare Systems;Heart Diseases;Hospitalization;Hospitals;human old age (65+);Human Resources;implementation science;Improve Access;improved;improved outcome;Infrastructure;innovation;inpatient service;insight;interest;Internist;Interview;Investments;Learning Skill;Life Expectancy;Malignant Neoplasms;Measures;medical specialties;Medicare claim;Mentors;Mentorship;Methods;Modeling;Morbidity - disease rate;mortality;multidisciplinary;novel;novel strategies;older adult;Outcome;Patient-Focused Outcomes;Patients;Pattern;payment;Pennsylvania;Physicians;Population;preservation;programs;prospective;Qualitative Methods;Qualitative Research;Quasi-experiment;readmission rates;Research;Research Methodology;Research Personnel;response;Risk;Rural;rural area;Rural Community;rural disparities;Rural Health;rural healthcare;Rural Hospitals;Rural Population;Site;skills;Source;Stroke;Surveys;System;Time;Training;treatment as usual;trend;United States;Universities;urban disparity;urban health disparities;Visit

PROJECT_TITLE: Improving Access to Care and Chronic Condition Management for Rural Older Adults in the US

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Behavior and Social Science of Aging Study Section[NIA-S]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: LOS ANGELES

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE  We all develop from a single cell to a fully-formed human with trillions of cells, during which process the DNA duplex experiences various types of spontaneous damage. Incorrect repair of spontaneous DNA breaks can lead to various types of genome alterations and instability. Here, we develop and apply high-throughput single- cell sequencing technologies to study how the repair of DNA breaks causes error-free and mutational genome rearrangements, and to better understand effects from genomic contexts, genetic mutations and tissue-of-origin.

PI_NAMEs: YIN, YI  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: 3-Dimensional;Address;Affect;Alleles;Area;Automobile Driving;Biochemical Process;Biological Assay;Cell Death;Cell Line;cell type;Cells;Cellular Assay;Cicatrix;cost effective;detection assay;Diploidy;DNA;DNA Double Strand Break;DNA Repair;DNA Sequence Alteration;Embryo;Embryonic Development;Event;experience;Genes;Genetic;Genome;genome integrity;genome-wide;Genomic Instability;Genomics;Homologous Gene;homologous recombination;Human;Hybrids;in vivo;knock-down;Lead;Lesion;Malignant Neoplasms;Mammalian Cell;Maps;Meiosis;Methods;Mitotic;multiple omics;Mus;mutant;Mutation;Outcome;Pathway interactions;Process;repaired;Replication Initiation;RNA;scale up;single cell sequencing;Sister Chromatid;System;Technology;Testing;Tissues;tool;tumorigenesis;Variant;Vision;Yeasts

PROJECT_TITLE: Understanding spontaneous mitotic crossover by single-cell multi-omics

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


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Liver Cancer;Liver Disease;Rare Diseases

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Tumor-associated macrophages play an important role in promoting tumor growth, angiogenesis, metastasis and immune evasion. However, how tumor-associated macrophages regulate anti-tumor immunity within the tumor microenvironment remains largely unknown. The proposed work will study the role of tumor-associated macrophages in inducing intraturmoral T cell dysfunction and develop novel strategies targeting tumor- associated macrophages for treating cancer.

PI_NAMEs: HUANG, XIAOPEI  (contact)

PROJECT_TERMS: angiogenesis;Anti-Inflammatory Agents;anti-PD-L1;anti-tumor immune response;antitumor effect;autocrine;cancer infiltrating T cells;CD8-Positive T-Lymphocytes;Cell Differentiation process;Cell Proliferation;Cells;Chimera organism;CXCL10 gene;CXCL9 gene;Data;Development;Engineering;Erinaceidae;exhaustion;Functional disorder;Heterogeneity;Human;Immune;immune checkpoint;Immune Evasion;Invaded;Ligands;liver cancer model;Macrophage;Malignant Breast Neoplasm;Malignant neoplasm of brain;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Modeling;Mus;Myeloid Cells;Neoplasm Metastasis;novel;novel strategies;overexpression;paracrine;Pathway interactions;PD-1 blockade;Phenotype;Play;Primary carcinoma of the liver cells;Production;programmed cell death ligand 1;recruit;Regulation;Role;SHH gene;Signal Transduction;Skin Cancer;smoothened signaling pathway;Solid Neoplasm;Stromal Cells;Stromal Neoplasm;subcutaneous;T cell infiltration;T-Lymphocyte;Testing;Therapeutic;Tissues;transcription factor;transcriptome;tumor;tumor growth;Tumor Immunity;tumor microenvironment;Tumor Promotion;Tumor-associated macrophages;Tumor-Derived;tumorigenesis;Up-Regulation;Work

PROJECT_TITLE: Regulation of tumor-infiltrating T cells by macrophages


ORG_CITY: CHICAGO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The proposed study is to use integrated experimental and computational genomics approaches to characterize the functional roles of newly identified short open reading frames (sORFs) in cells. The work will reveal basic molecular mechanisms mediating sORF expression and conservation, as well as the tight coupling between sORF translation vs. other layers of peptide and RNA metabolic processes.

PI_NAMEs: JI, ZHE  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: 5' Untranslated Regions;Automobile Driving;Biological;Biological Process;Cell Proliferation;Cells;Computational algorithm;Coupling;Data;Degradation Pathway;Development;Disease;Disease Progression;Elements;Eukaryota;Evolution;frontier;Genetic study;Genome;Genomic approach;insight;Mediating;Metabolism;Modeling;Molecular;Normal Range;novel;Open Reading Frames;Other Genetics;Peptides;Pseudogenes;Research;ribosome profiling;RNA;RNA Stability;Role;Translating;Translations;Untranslated RNA;Work

PROJECT_TITLE: Characterizing functional translation in putative 'noncoding' regions of a genome

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


PHR: NARRATIVE Despite recent progress in immune-oncology, most patients with solid tumors still do not respond to Immune checkpoint blockade and adoptive T cell based therapies. We propose to image signaling activity through the IDO/TDO-Kyn-AHR pathway, to optimize the timing (scheduling) of combination drug treatment (treatments targeting this pathway combined with immune based therapies).

PI_NAMEs: KESHARI, KAYVAN R;MERGHOUB, TAHA  (contact)

PROGRAM_OFFICER_NAME: LIN, CHARLES

PROJECT_TERMS: Address;Adoptive Transfer;Agonist;antagonist;Antigens;Aryl Hydrocarbon Receptor;Basic Science;Biological;Biological Assay;Biological Markers;Biological Models;Biosensor;cancer cell;Cancer Model;cancer type;Catabolism;CD4 Positive T Lymphocytes;CD8B1 gene;cell type;Cells;Characteristics;Clinical;clinical translation;clinically relevant;combinatorial;Combined Modality Therapy;Communication;CTLA4 blockade;Data;design;Dioxins;Drug Combinations;effector T cell;Elements;Enhancers;Enzymes;Evaluation;experience;FOXP3 gene;Generations;Genetic Transcription;Glucose;Glutamine;Human;Image;image guided;Immune;immune checkpoint blockade;immune resistance;Immunooncology;Immunosuppression;Immunotherapy;improved;In Vitro;in vivo;Inflammatory;Infrastructure;Interdisciplinary Study;Kinetics;Kynurenine;Letters;Link;Macrophage;Malignant Neoplasms;Mediating;Metabolic;Modeling;Monitor;Myelogenous;Myeloid-derived suppressor cells;Nature;neoplastic cell;novel;Nutritional;overexpression;Pathway interactions;Patients;personalized approach;Pharmacotherapy;Phenotype;Play;Population;pre-clinical;Pre-Clinical Model;prevent;Production;programmed cell death protein 1;Publications;rational design;Receptor Activation;Receptor Inhibition;Records;recruit;Regulatory T-Lymphocyte;Reporter;Research;Resistance;resistance mechanism;response;Role;Schedule;Signal Transduction;Solid Neoplasm;success;System;T cell anergy;T cell therapy;T-Lymphocyte;targeted agent;Therapeutic Intervention;therapy design;therapy resistant;Time;transcription factor;Tryptophan;Tryptophan 2,3 Dioxygenase;Tryptophanase;tumor;Tumor Cell Line;Tumor Immunity;tumor microenvironment;tumor progression;Tumor-associated macrophages

PROJECT_TITLE: Image-guided Trp-IDO/TDO-Kyn-AHR pathway inhibition, combined with immunotherapy

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


NIH_SPENDING_CATS: Aging;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research

ORG_CITY: CAMBRIDGE

ORG_NAME: NATIONAL BUREAU OF ECONOMIC RESEARCH

PHR: OTHER PROJECT INFORMATION – Project Narrative - Relevance The NBER summer institute workshops in aging and health care provide an annual forum for researchers to present and discuss cutting-edge scientific research in this field, and to interact with other scholars in an environment that enhances their ongoing work. The substantive themes addressed in these workshops represent some of the nation’s biggest health challenges and opportunities. In each area, the potential for scientific findings that improve health outcomes is significant, and the opportunity to discuss research in progress enriches the scientific productivity of participating investigators.

PI_NAMEs: SKINNER, JONATHAN S (contact)

PROJECT_TERMS: Address;Aging;aging population;aging related;Alzheimer's disease related dementia;Area;behavior change;Communities;Companions;cost;Country;Data Analytics;Decision Making;Demography;Development;Discipline;economic evaluation;Economics;Ecosystem;Educational workshop;Environment;Funding;Goals;Government Agencies;Grant;Health;health care service organization;health inequalities;Health trends;Healthcare;improved;Information Technology;innovation;Institution;interest;Medical;meetings;Methodology;Older Population;Outcome;Participant;Personal Satisfaction;Productivity;programs;Research;Research Activity;Research Personnel;Research Project Grants;Research Technics;Resources;summer institute;summer research;Time;Training;Training Activity;Training Programs;Travel;United States;Universities;Work

PROJECT_TITLE: Summer Institute Workshop in Aging and Health Care


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Childhood Leukemia;Clinical Research;Genetics;Hematology;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: PROJECT NARRATIVE In this proposal, we will examine the mechanisms by which inherited variants in the gene ETV6 contribute to development of B-acute lymphoblastic leukemia (B-ALL), the commonest childhood cancer and leading cause  of cancer-related death in children. Through these studies, we will define how ETV6 variants influence normal blood cell development and participate in progression to leukemia. This proposal has relevance to public health because it will improve our understanding of B-ALL and thereby inform the creation of new and more effective ways to classify, treat, and possibly also prevent this prevalent and at times deadly childhood cancer.

PI_NAMEs: NICHOLS, KIM ERIKA (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Acute Lymphocytic Leukemia;Affect;ATAC-seq;autosome;B cell differentiation;B-Cell Acute Lymphoblastic Leukemia;B-Cell Development;B-Lymphocytes;Binding;Biological Assay;Biological Models;Biology;Blood Cells;Cancer Biology;Cancer Etiology;cancer predisposition;Cancer-Predisposing Gene;Cell Count;Cell Differentiation process;cell growth;Cell Line;Cells;cellular development;Child;Childhood;Childhood Acute Lymphocytic Leukemia;childhood cancer mortality;ChIP-seq;Chromatin;Classification;Clinical;cohort;Collaborations;Cytoplasm;Data;Databases;Defect;derepression;Development;disease classification;disease prognosis;DNA Binding;Dysplastic Megakaryocyte;Epigenetic Process;ETV6 gene;Event;Exhibits;Family;Gene Expression;Genes;Genetic;Genetic Transcription;Genetic Variation;genome sequencing;Germ Lines;Germ-Line Mutation;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Heterozygote;Human;human induced pluripotent stem cells;Impairment;improved;In Vitro;in vitro Assay;in vivo;Individual;induced pluripotent stem cell;Inherited;insight;Lesion;leukemia;Leukemic Hematopoietic Stem Cell;leukemogenesis;Literature;Malignant - descriptor;Malignant Childhood Neoplasm;Malignant Neoplasms;Modeling;mouse model;Mus;Mutant Strains Mice;Mutate;novel;Pathogenesis;Pathogenicity;Pathway interactions;Patients;personalized management;Phenotype;Physicians;Physiology;Population;Positioning Attribute;Predisposition;prevent;progenitor;programs;Proteins;Public Health;Recurrence;Reporting;Saint Jude Children's Research Hospital;Sampling;Scientist;Somatic Mutation;stem cell population;stem cells;Syndrome;Testing;Thrombocytopenia;transcription factor;Transcription Repressor;transcriptome;transcriptome sequencing;transmission process;treatment optimization;tumorigenesis;Variant;whole genome

PROJECT_TITLE: Pathogenesis of ETV6-Related Acute Lymphoblastic Leukemia

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Genetics;Hepatitis;Liver Disease;Substance Misuse

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: NARRATIVE  Alcohol-associated hepatitis (AH) is a form of subacute liver failure with high mortality and limited treatment options. We hypothesize that HNF4-dependent cholesterol toxicity is a critical pathogenic driver resulting in liver failure in AH. We propose to rigorously interrogate pathways of cholesterol homeostasis and test a strategy to restore cholesterol homeostasis by modulating the expression of HNF4α, the master transcription factor of liver cells.

PI_NAMEs: JIANG, ZHENGHUI GORDON (contact)

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: Acute;Acyltransferase;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;Atlases;Bile Acid Biosynthesis Pathway;Bile Acids;Binding;Blood;Cells;Cholestasis;Cholesterol;Cholesterol 7-alpha-Monooxygenase;Cholesterol Homeostasis;Chronic;Development;Disease;disease model;efficacy testing;Enzymes;Esterification;Exhibits;Experimental Models;feeding;first-in-human;Functional disorder;Hepatitis;Hepatocyte;hepatocyte nuclear factor;Hepatotoxicity;HNF4A gene;Human;Impairment;In Vitro;in vivo;Individual;Knowledge;Lecithin;Link;Lipoproteins;Liver;Liver diseases;Liver Failure;Maps;Messenger RNA;Metabolic Pathway;Modeling;mortality;mouse model;multidisciplinary;multimodality;multiplexed imaging;Mus;novel;novel therapeutic intervention;Nuclear RNA;Pathogenesis;Pathogenicity;Pathway interactions;Patients;pre-clinical;predict clinical outcome;Production;Protein Isoforms;Proteins;Regulatory Pathway;Resolution;reverse cholesterol transport;RNA;RNA Interference;Route;Sampling;Scientist;screening;single nucleus RNA-sequencing;success;targeted treatment;Technology;Testing;Therapeutic;therapeutic target;tool;Toxic effect;transcription factor;transcriptome sequencing;transcriptomics;Transgenic Model;Transportation;Treatment Efficacy;treatment strategy;Up-Regulation;uptake;Very low density lipoprotein

PROJECT_TITLE: Cholesterol toxicity in alcohol-associated hepatitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-KUDS-Y(05)]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Gene Therapy;Genetics;Infectious Diseases;Microbiome

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE The mammalian gastrointestinal tract is home to a diverse community of microorganisms whose roles in human health and behavior are being increasingly appreciated, yet few tools are available for genetically modifying this crucial environmental niche with gene- and species-level control. The proposed project aims to develop a new platform technology for precision microbiome engineering that combines programmable, CRISPR RNA-guided integrases with broadly transmissible vectors for highly specific, in situ metagenome alteration. In addition to laying a foundation for future biological insights on host-microbiome metabolism, this work will reveal new therapeutic avenues for inactivating multidrug resistance genes in bacterial pathogens, a looming global health threat.

PI_NAMEs: STERNBERG, SAMUEL HENRY;WANG, HARRIS H (contact)

PROGRAM_OFFICER_NAME: DARINGER, NICHOLE MARIE

PROJECT_TERMS: Address;Algorithm Design;Area;Automobile Driving;Bacteria;bacterial community;Bacterial Genes;Bacterial Genome;base editor;Basic Science;Behavior;bile acid metabolism;bile salts;Biological;Biological Models;Candidate Disease Gene;carbapenemase;Catalogs;Cells;Central Nervous System;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Collection;Communities;Complex;Coupled;CRISPR-associated transposons;CRISPR/Cas technology;Custom;Data;data integration;Data Pooling;Data Set;design;Directed Molecular Evolution;Disease;disease model;DNA;DNA Double Strand Break;Drug resistance;dysbiosis;Elements;Engineering;Environment;Escherichia coli;Exhibits;experimental study;flexibility;Foundations;Future;gain of function;Gastrointestinal tract structure;gene editing technology;Gene Modified;Gene Silencing;Genes;genetic approach;Genetic Engineering;genetic manipulation;genetic payload;Genome;Genome engineering;genome-wide;global health;Gnotobiotic;Guide RNA;gut microbiome;Health;Home;homologous recombination;Horizontal Gene Transfer;host microbiome;Human;Human Engineering;Hydrolase;Hyperactivity;Immunity;In Situ;In Vitro;in vivo;Industrialization;innovation;Insertional Mutagenesis;insight;Integrase;interest;Klebsiella oxytoca;Klebsiella pneumoniae;Knock-out;Laboratories;loss of function;Mammalian Cell;metabolic engineering;Metabolism;metagenome;Metagenomics;Methods;Microbe;microbial community;microbiome;microbiome composition;microbiota;microorganism;Modification;mouse model;Multidrug Resistance Gene;Mus;Mutation;Names;Nervous System Physiology;next generation;novel therapeutic intervention;novel therapeutics;Nucleotides;Orthologous Gene;Outcome;pathogen;pathogenic bacteria;Pathway interactions;Performance;Physiological;Plasmids;Play;prevent;prime editor;Pseudomonas putida;Regulatory Element;repaired;Research;resistance gene;resistome;reverse genetics;RNA library;Role;Scientist;screening;site-specific integration;Specificity;synthetic biology;System;Technology;technology platform;Therapeutic;Time;tool;transmission process;Transposase;Variant;vector;Vibrio cholerae;Work

PROJECT_TITLE: A high-performance and versatile technology for precision microbiome engineering

STUDY_SECTION: GCAT

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


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

ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: PROJECT NARRATIVE Defects in replication stress response, which promotes fork stability and genome integrity when DNA replication is challenged, can cause diseases associated with developmental abnormalities, premature aging and cancer predisposition. This proposal focuses on the functional characterization of replication fork components, to uncover new proteins and regulatory mechanisms that promote accurate DNA replication in the context of replication stress. Since replication stress drives cellular transformation, investigating replication stress response pathways can lead to critical drug discoveries targeted for cancer chemotherapies.

PI_NAMEs: DUNGRAWALA, HUZEFA MANNAN (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;age acceleration;Area;biological adaptation to stress;cancer predisposition;Cell Cycle;Cells;Chemoresistance;Chemotherapy-Oncologic Procedure;Clinical Trials;Complex;Data Set;Defect;design;Development;Disease;Dissociation;DNA biosynthesis;DNA Damage;DNA Repair;DNA replication fork;drug discovery;effective therapy;Failure;Genetic Transcription;Genome;genome integrity;Goals;Human;inhibitor;insight;Macromolecular Complexes;Maintenance;Malignant Breast Neoplasm;Mediator;metaplastic cell transformation;Modeling;Molecular;Pathway interactions;Phosphorylation;Premature aging syndrome;prevent;programs;Proteins;Proteomics;recruit;Regulation;Repetitive Sequence;replication stress;Research;Resources;screening;Signal Transduction;Therapeutic;Work

PROJECT_TITLE: Molecular Mechanisms of Replication Stress Response


ADMINISTERING_IC: AI

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Hepatitis - C;Immunization;Immunotherapy;Infectious Diseases;Liver Disease;Vaccine Related

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: The role of functionally distinct hepatic T cell subsets in providing protective immunity from hepatotropic viruses, such as hepatitis C virus (HCV), or mediating liver pathology during inflammatory liver disease is poorly defined. Using a mouse model of an HCV-related virus we will investigate the functional properties and potential interplay of distinct type 1 and type 2 T cell and natural killer T (NKT) cell subsets during different stages of hepacivirus infection in vivo. Our results should reveal new concepts of hepatic T cell immunity with implications for the development of HCV vaccine strategies and new therapeutic options for liver disease.

PI_NAMEs: BILLERBECK, EVA  (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Acute;acute infection;Address;Adoptive Cell Transfers;Animal Model;Biological;Biology;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Chronic;Chronic Hepatitis C;chronic infection;chronic liver inflammation;Cirrhosis;comparison control;cytokine;Cytotoxic T-Lymphocytes;Data;Development;Disease Progression;end stage liver disease;Epitopes;Equilibrium;experimental study;Fibrosis;Flow Cytometry;Generations;Hepatic;Hepatitis B Virus;Hepatitis C;Hepatitis C Vaccination;Hepatitis C Vaccine;Hepatitis C virus;Hepatitis C-Like Viruses;Hepatocyte;high dimensionality;Human;Immune;Immune response;Immunity;Immunocompetent;Immunologics;Immunology;immunoregulation;Immunotherapeutic agent;in vivo;Infection;Inflammation;Inflammatory;innovation;insight;Interleukin-13;Interleukin-4;Kinetics;Knockout Mice;Link;Liver;Liver diseases;Liver Fibrosis;liver injury;Lymphocyte Subset;Mediating;Mediator;Memory;Metabolic stress;MHC Class I Genes;Modeling;mouse model;Mouse Strains;Mus;novel;novel therapeutics;Pathology;Patients;Phenotype;Play;polarized cell;Predisposition;Primary carcinoma of the liver cells;Property;Rattus norvegicus;repaired;response;restraint;Rodent;Role;Sampling;secondary infection;single-cell RNA sequencing;Steatohepatitis;T cell response;T-Cell Activation;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic;Time;tissue repair;Tissues;Toxin;transcriptome;Translating;vaccination strategy;vaccine strategy;Viral;Viral hepatitis;Virus;Virus Diseases

PROJECT_TITLE: New insights into the functional diversity of the hepatic antiviral T cell response during hepacivirus infection in vivo

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Estrogen;Genetics;Human Genome;Women's Health Research

ORG_CITY: MAYWOOD

ORG_DEPT: BIOLOGY

ORG_NAME: LOYOLA UNIVERSITY CHICAGO

PHR: Project Narrative Activating somatic mutations to estrogen receptor alpha (ERα) enable hormone therapy resistance and significantly contribute to breast cancer mortality. We recently identified a novel therapeutic structural interaction that correlates with improved anti-cancer activities for Y537S ERα, the most aggressive and drug-resistant of the known mutants. We will use a library of over 100 structurally diverse ERα-targeted small molecule antagonists to reveal the interplay between Y537S ERα structure, genomic actions, and anti-cancer activities to overcome hormone therapy resistance in breast cancer.

PI_NAMEs: FANNING, SEAN WILLIAM (contact)

PROGRAM_OFFICER_NAME: GREENBERG, WILLIAM A

PROJECT_TERMS: Address;Adopted;Affect;antagonist;anticancer activity;appropriate dose;Binding;Breast Cancer Cell;breast cancer genomics;Breast Cancer Model;Breast Cancer therapy;Cancer Etiology;CDK4 gene;Cessation of life;Clinical;Data;Development;Dimerization;Disease Progression;Drug Kinetics;Drug resistance;Emergency Department patient;ESR1 gene;Estrogen Antagonists;Estrogen receptor positive;Estrogen Receptors;Fulvestrant;Genes;Genetic Transcription;Genome;genome-wide;Genomics;Growth;hormone therapy;Hormones;Hydrogen Bonding;improved;In Vitro;in vivo;inhibitor;insight;Legal patent;Libraries;Ligand Binding;Ligand Binding Domain;Ligands;Malignant Breast Neoplasm;MCF7 cell;Missense Mutation;Modeling;Molecular Conformation;mortality;mutant;Mutation;Neoplasm Metastasis;next generation;novel;novel therapeutics;Oral;overexpression;Pathology;patient derived xenograft model;Patients;Pharmaceutical Preparations;pharmacologic;Population;Pre-Clinical Model;pressure;prevent;programs;Proliferating;protein protein interaction;Proteins;receptor;Resistance;Resolution;response;Roentgen Rays;Route;Selective Estrogen Receptor Modulators;Series;Shapes;side effect;small molecule;Somatic Mutation;Structure;Structure-Activity Relationship;Tamoxifen;Therapeutic;therapeutic target;Tissues;Transcription Coactivator;Transcriptional Regulation;transcriptome;Treatment Efficacy;tumor;tumor growth;tumor xenograft;United States

PROJECT_TITLE: Structural-Transcriptional Relationships that Improve Y537S Estrogen Receptor Antagonism

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


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

ORG_CITY: NEW YORK

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: PROJECT NARRATIVE  The proposed research is relevant to public health because understanding the mechanisms linking iron to Alzheimer's disease will provide evidence for the development of new therapeutics targeting iron, which may slow cognitive decline. This research is relevant to the NIA's mission to support research to improve the health and well-being of older people.

PI_NAMEs: CHIANG, GLORIA CHIA-YI (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: abeta deposition;Acceleration;Affect;Age;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer’s disease biomarker;Amyloid;Amyloid beta-42;Amyloid beta-Protein;Amyloid deposition;Animal Model;Apolipoprotein E;Atrophic;Autopsy;Brain;brain iron;Brain region;cerebral atrophy;Cerebrospinal Fluid;Cerebrum;Clinical Trials;Cognition;Cognitive;cognitive testing;cohort;Dementia;Development;Disease;Elderly;Enrollment;frontal lobe;Glutathione;Health;Human;Hydroxyl Radical;hyperphosphorylated tau;Imaging Techniques;Impaired cognition;improved;In Vitro;in vivo;in vivo imaging;Individual;Iron;Iron Chelating Agents;Iron Chelation;Isoprostanes;Knowledge;Lateral;Link;Lipid Peroxidation;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Magnetic Resonance Spectroscopy;Maps;Measures;Memory;Memory Loss;Microglia;mild cognitive impairment;Mission;Modeling;Monitor;Nerve Degeneration;neurofibrillary tangle formation;neuron loss;Neuronal Injury;neuropsychiatric disorder;new therapeutic target;Nitrogen;Older Population;oxidative damage;Oxidative Stress;Oxygen;Parietal Lobe;Pathogenesis;Pathologic;Personal Satisfaction;Persons;Pittsburgh Compound-B;Positron-Emission Tomography;preclinical study;Predisposition;Process;prospective;Prospective Studies;Prostaglandins;Protons;Public Health;Reaction;Research;Research Support;Role;Sampling;Senile Plaques;Specimen;targeted treatment;tau Proteins;tau-1;Temporal Lobe;Testing;therapeutic target;Therapeutic Trials;Thinness;Tissues;Tracer

PROJECT_TITLE: The effects of iron on oxidative stress and Alzheimer's biomarkers in amyloid-positive and negative elderly normal

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE  Attention is critical in our everyday life and serves as an important building block of many of our more complex behaviors. The proposed research will identify the cellular and circuit level signatures of successful attention through examination of neuronal activity in typically functioning mice and mutant mouse lines with attention impairments. Results generated from this proposal will answer fundamental questions about how the brain supports attention and provide a basis for the development of effective therapeutics for attentional impairments across disease states.

PI_NAMEs: FERGUSON, BRIELLE  (contact)

PROGRAM_OFFICER_NAME: ROSSI, ANDREW F

PROJECT_TERMS: Address;Attention;autism spectrum disorder;Behavior;behavioral response;Biological Assay;Brain;cell type;Cells;Cognition;comorbidity;Complex;Cues;Data;design;Development;Disease;Dissection;Epilepsy;Fiber;flexibility;Functional disorder;Genetic;hippocampal pyramidal neuron;Image;Impaired cognition;Impairment;in vivo;Individual;Interneurons;Length;Life;Link;Measures;Medial;Mediating;Mental Depression;Mental disorders;Microscope;miniaturize;Monitor;mouse model;Mus;Mutant Strains Mice;neuronal cell body;Neurons;novel;optogenetics;Parvalbumins;Perception;Performance;Phase;Photometry;Physiological;Physiology;Play;Population;Prefrontal Cortex;Process;Public Health;recruit;Regulation;Research;response;Role;Schizophrenia;selective attention;Signal Transduction;Slice;Somatostatin;Source;Specificity;Structure;sustained attention;Techniques;Testing;Thalamic structure;therapeutic target;therapeutically effective;Training;Vasoactive Intestinal Peptide;Visual attention;Work

PROJECT_TITLE: Identifying prefrontal signatures of successful and dysfunctional attention

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: COLLEGE PARK

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: PROJECT NARRATIVE  Oxycodone seeking progressively increases after prolonged abstinence from drug self-administration. This proposal uses a rat model to investigate the role of March5 and associated mitochondrial dynamics underlying this “incubation of oxycodone craving”. These studies will advance our understanding of molecular mechanisms underlying oxycodone relapse and may help us uncover potential therapeutic targets for oxycodone relapse prevention.

PI_NAMEs: LI, XUAN ANNA (contact)

PROGRAM_OFFICER_NAME: BORGMANN, KATHLEEN RUTH

PROJECT_TERMS: Abstinence;activity marker;addiction;Anatomy;Behavior;Biochemical;Cell Physiology;Clinical;cocaine relapse;cocaine seeking;craving;Cues;Data;drug abstinence;Drug Addiction;drug craving;Drug usage;Dynamin;Exploratory/Developmental Grant;Exposure to;Extinction;Frequencies;genetic manipulation;Incubated;innovation;Intervention;Label;Lead;Length;Link;Literature;male;Mediating;Mediator;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;Molecular Target;Morphine;Morphology;mRNA Expression;multicatalytic endopeptidase complex;Mus;neuromechanism;Neurons;Nucleus Accumbens;Opiate Addiction;Opioid;opioid epidemic;Oxycodone;oxycodone seeking;oxycodone self-administration;Pharmaceutical Preparations;pharmacologic;Play;prescription opioid abuse;prolonged abstinence;protein degradation;protein expression;Proteins;psychostimulant;Publishing;Rattus;Regulation;Relapse;relapse prevention;Research;Rewards;Role;Saline;Self Administration;System;Testing;therapeutic target;Time;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;Viral;Viral Vector;Work

PROJECT_TITLE: March5 and Associated Mitochondrial Dynamics in Incubation of Oxycodone Craving

STUDY_SECTION: MCNP

STUDY_SECTION_NAME:
Molecular and Cellular Neuropharmacology Study Section
[MCNP]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Pediatric

ORG_CITY: BALTIMORE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Understanding death rates by cause and age in children is critical to guide child survival policymaking and resource allocation, particularly in low resource settings where most deaths happen unregistered or undocumented. Improving age- and cause-specific under-five mortality estimation requires improved understanding of data quality while maintaining a focus on efficiency and cost effectiveness of data collection.

PI_NAMEs: LIU, LI  (contact);MCCORMICK, TYLER

PROGRAM_OFFICER_NAME: CHINN, JUANITA JEANNE

PROJECT_TERMS: 5 year old;Accounting;Address;Adoption;Adult;Age;age group;age related;Autopsy;Azithromycin;Bangladesh;Bayesian Modeling;Cause of Death;Cessation of life;Child;Childhood;Classification;Cluster randomized trial;Communities;Computer software;Congenital Abnormality;contextual factors;cost effectiveness;Country;Custom;Data;Data Analyses;Data Collection;data management;data quality;Death Rate;Decision Making;Development;Diarrhea;Disease;Elderly;Epidemiology;Error Sources;Evaluation;experience;flexibility;Focus Groups;Frequencies;Future;Government;Health;Heart Diseases;Heterogeneity;Household;Impact evaluation;improved;Infrastructure;innovation;International;Intervention;Investments;Life;low income country;Malaria;Malaria Vaccines;Measurement;Meningitis;Methodology;Methods;Modeling;mortality;Mozambique;National Institute of Child Health and Human Development;neonate;open source tool;Periodicals;Pneumonia;Policies;Policy Making;Prevalence;Program Effectiveness;programs;Randomized, Controlled Trials;Reference Standards;Research;Resolution;Resource Allocation;Resource-limited setting;Risk;Sampling;scale up;Series;Site;Source;Specificity;Statistical Models;Surveys;System;theories;tool;Training;Uncertainty;validation studies;Variant;verbal;Work

PROJECT_TITLE: Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries

STUDY_SECTION: SSPA

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


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_CITY: SAINT LOUIS

ORG_NAME: SAINT LOUIS UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative Cellular integration of hepatitis B virus (HBV) represents an alternative biological source for HBV surface antigen (HBsAg) that is closely associated with clinical outcomes in patients with chronic HBV infection. Currently, the contribution of HBV integration to HBsAg remains an elusive issue. A non-invasive method to quantitate integration-derived HBsAg, as proposed in the current application, would be extremely valuable in translational research, clinical trials, and patient management for the globally 257 million people infected with HBV.

PI_NAMEs: FAN, XIAOFENG  (contact)

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Address;Antigens;Biological;Blood specimen;Characteristics;Chronic Hepatitis B;Circular DNA;Circulation;Clinical;Clinical Trials;cohort;Cohort Studies;Confidence Intervals;Data;Data Analyses;deoxyguanosine triphosphate;Digestion;digital;DNA;Exclusion;experimental study;Family;Genetic Transcription;Hepatitis B;Hepatitis B e Antigens;Hepatitis B Infection;Hepatitis B Virus;Hepatocarcinogenesis;Hepatology;Human;Human Genome;Immune;Immunosuppression;Incidence;insight;Interruption;Knowledge;Legal patent;Liver;Measurement;Measures;member;Methods;next generation sequencing;North America;novel;Nuclear;Outcome;Pathogenesis;Patients;Persons;Phenotype;Preparation;Primary carcinoma of the liver cells;Procedures;promoter;Proteins;Quantitative Reverse Transcriptase PCR;reference genome;Research;Resistance;Sampling;Serum;simulation;Source;Specimen;Study of serum;Surface Antigens;Tissue Sample;Tissues;Transcript;transcriptomics;Transgenic Model;Translational Research;United States National Institutes of Health;Validation;validation studies;Viral;viral DNA;Viral Genome;viral RNA;Virus Integration

PROJECT_TITLE: Transcriptomic Quantitation of Hepatitis B Virus Surface Antigen from Integration

STUDY_SECTION: EDIT

STUDY_SECTION_NAME: Etiology, Diagnostic, Intervention and Treatment of Infectious Diseases Study Section[EDIT]


ORG_CITY: WINSTON-SALEM

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: Chronic pain from injury is a major source of disability and an enormous economic and social burden. There is a clear need to identify disease-modifying therapies that prevent or reduce chronic pain after injury, including major surgery. This P01 will study oxytocin as a potential disease-modifying agent across rodents and humans, identifying critical pharmacokinetic, physiological, and behavioral measures that contribute to mitigating chronic pain development and speeding resolution of pain after injury.

PI_NAMEs: EISENACH, JAMES ;MARTIN, THOMAS JEFFREY (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Acute;Acute Pain;addiction;Affective;Analgesics;Animals;Anti-Anxiety Agents;Anxiety;Area;Behavior;behavior measurement;Behavioral;Blood;Brain;brain tissue;Central Nervous System;central sensitization;Cesarean section;Chronic;chronic pain;Clinical;clinical practice;Clinical Research;Cognitive;Computers;Data;desensitization;Development;disability;Disease;Dose;Drug Exposure;Drug Kinetics;Economics;efficacy evaluation;electrical property;Feasibility Studies;Female;Fiber;Formulation;Fright;Functional disorder;Goals;Human;Hypersensitivity;improved;in vivo;Infusion procedures;Injury;Intramuscular;knee replacement arthroplasty;Knowledge;Literature;male;Mechanoreceptors;Methods;Modeling;multimodality;Nature;Nerve Block;Nerve Fibers;Nervous System;Neuropathy;neurophysiology;neuroprotection;Nociception;Operative Surgical Procedures;Oxytocin;Pain;pain behavior;pain chronification;pain reduction;Pain Research;Patients;Pelvis;Penetration;Peripheral;Peripheral Nerves;Persons;pharmacodynamic model;pharmacokinetics and pharmacodynamics;Physical therapy;Physiological;Physiology;postoperative recovery;pre-clinical;prevent;Process;Psychophysics;Rattus;Recovery;Reporting;Research;Resolution;response;Rodent;Role;Sensory;sensory stimulus;sex;Site;Sleep;social;Social Behavior;Source;Speed;Sweden;Therapeutic;Time;tool;translational approach;translational study;Translations;transmission process;Trust;Universities;verbal;vibration perception;Woman

PROJECT_TITLE: Oxytocin: a pain disease-modifying agent in the nervous system after injury


PHR: The Administrative Core coordinates all activities of the P01 across 9 investigators and 3 institutions. This includes assurance of high-quality standards and rigorous approaches, tracking progress, providing a structure for resource allocation, and providing mechanisms for resolving problems and assuring integration across all projects and cores.

PI_NAMEs: MARTIN, THOMAS JEFFREY (contact)

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Brain Disorders;Cannabidiol Research;Cannabinoid Research;Drug Abuse (NIDA only);Genetics;HIV/AIDS;Human Genome;Infectious Diseases;Natural Products;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Substance Misuse

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE The effects of cannabis on the brain of people living with HIV are controversial, underscoring the need for well-controlled studies generating reproducible data from specific cannabinoids, brain regions, and specific brain cell types. The research proposed in this application harnesses advances in single cell methods to generate data from unique regions of the brain where neurogenesis occurs to improve our understanding of the effects of HIV and cannabinoids.

PI_NAMEs: CORLEY, MICHAEL JAY;NDHLOVU, LISHOMWA C (contact);WILLIAMS, DIONNA WHITNEY

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Address;adult neurogenesis;Age;Anti-Inflammatory Agents;antiretroviral therapy;Area;Autopsy;Binding Sites;bioinformatics pipeline;Brain;brain cell;Brain region;brain tissue;Cannabidiol;Cannabinoids;Cannabis;Cell Nucleus;cell type;Cells;Cellular Assay;Central Nervous System;Cerebrospinal Fluid;Cerebrum;Chromatin;comorbidity;Controlled Study;Data;Data Set;dentate gyrus;Disease;DNA-Binding Proteins;Dose;Drug abuse;Epigenetic Process;epigenomics;experience;Exposure to;Frequencies;Funding;Gene Expression;Genes;Genetic Transcription;genome-wide;Genomics;Goals;Hippocampus;histone modification;HIV;HIV Infections;HIV-associated cognitive impairment;Human;Immunohistochemistry;Impairment;improved;Individual;Inflammation;Interferons;Knowledge;lateral ventricle;marijuana use;marijuana use disorder;Measures;Mediator;Medicine;Methods;Microglia;Modeling;multiple omics;Myelogenous;nerve stem cell;neuroAIDS;Neurobiology;neurogenesis;neuroinflammation;neuron loss;Neuronal Injury;Neurons;Neuropathogenesis;neuroprotection;nonhuman primate;Oral;Oral Administration;Organoids;Outcome;Pathogenicity;Pathway interactions;Pattern;Persons;pharmacologic;Pharmacology;programs;Proliferating;Protocols documentation;Proviruses;Recreation;Regimen;Reproducibility;Research;Research Personnel;response;Risk;RNA;Role;single cell technology;SIV;Specimen;Structure;subventricular zone;Tetrahydrocannabinol;Therapeutic;Tissue Sample;Tissues;Toxic effect;Transcript;transcriptomics;Transposase;United States National Institutes of Health;Validation;Viral;Viral Load result;Virus;XCL1 gene

PROJECT_TITLE: Elucidating single cell changes in neurogenic brain regions during HIV and cannabinoid exposure


NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Neurosciences;Pain Research

PHR: The Animal Core will provide essential services and facilities to the preclinical projects in a standardized and efficient manner, utilizing shared facilities, equipment, and personnel in a coordinated fashion. The services provided to each preclinical project include animal procurement, identification, transgenic colony management, surgical preparation and behavioral assessment. The Core will also standardize methods for collection of plasma and brain tissue for assessing oxytocin levels and for immunohistochemical verification of efficient viral vector transduction and ablation.

PI_NAMEs: PETERS, CHRISTOPHER MICHAEL (contact)

PROJECT_TERMS: Ablation;Affective;Anatomy;Animals;Behavior assessment;Behavior Control;behavior test;Behavioral;Behavioral Assay;Biochemical;Biohazardous Substance;Brain;brain tissue;Breeding;Catheterization;Collaborations;Collection;Complex;cost effective;Cryoultramicrotomy;Custom;Data;Data Analyses;Data Collection;data exchange;Databases;Disease;DNA Sequence;Electrophysiology (science);Ensure;Enterobacteria phage P1 Cre recombinase;Equipment;Equipment and supply inventories;femoral artery;Generations;Genotype;Human Resources;IACUC;Immunohistochemistry;in vivo;Individual;Injury;Label;Ligation;Maintenance;Mediating;Methods;microscopic imaging;Microscopy;Nervous System;Neurons;novel;offspring;Operative Surgical Procedures;Oxytocin;Pain;pain outcome;paraform;Perfusion;pharmacokinetics and pharmacodynamics;Plasma;Plasmids;Population;pre-clinical;preclinical study;Preparation;Procedures;programs;protein expression;Protocols documentation;Quality Control;Rat Transgene;Rattus;Regulatory Affairs;Research;Safety;Sampling;Scheme;Sensory;Serotyping;Services;Source;Spinal Cord;Spinal nerve structure;Standardization;Statistical Data Interpretation;Structure;Structure of jugular vein;Supervision;Tissue Banks;Tissue Harvesting;Tissue Sample;Tissues;Training;Transgenic Organisms;Vendor;Viral;Viral Packaging;Viral Vector

PROJECT_TITLE: Animal Core


PHR: The Pharmacokinetics/Pharmacodynamics Core will utilize data generated through Projects 1, 2 and 3 and the Animal Core to construct PK/PD models of oxytocin biodisposition and drug effect in rats and humans. These models will be subsequently used by Projects 1, 2 and 3 to determine the disease modification potential for oxytocin in mitigating the progression from acute to chronic pain, equating exposure levels across species, sex, and experimental paradigms.

PI_NAMEs: SHAFER, STEVEN LOUIS (contact)

PROJECT_TERMS: Acute;Acute Pain;Age;Animals;Behavior;Blood;Blood - brain barrier anatomy;Blood specimen;Brain;Central Nervous System;chronic pain;Clinical;clinical effect;clinical translation;Clinical Trials;Collaborations;Complex;Data;design;Disease;Dose;drug action;Drug Kinetics;Ensure;Equation;Goals;healing;Human;human subject;Injury;Intramuscular;Kinetics;mathematical model;Measurement;Measures;Modeling;Modification;Nervous System;neurophysiology;Nociception;Operative Surgical Procedures;Outcome Measure;Oxytocin;Pain;Pain Measurement;pain reduction;Patient Care;Peripheral;Pharmaceutical Preparations;pharmacodynamic model;Pharmacodynamics;pharmacokinetic model;pharmacokinetics and pharmacodynamics;pharmacologic;Plasma;programs;Rattus;Recovery;Regimen;Reproducibility;Research;Research Personnel;response;Role;Route;Sensory;Serum;sex;Site;Speed;subcutaneous;Therapeutic;Time;tissue injury;Tissues;Translations;uptake;Weight;Work

PROJECT_TITLE: Pharmacokinetics/Pharmacodynamics Core


NIH_SPENDING_CATS: Bioengineering;Chronic Pain;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects

PHR: NARRATIVE This project will examine the pharmacology and neurobiology of systemically administered OXT in the setting of nerve injury. We have shown that acute and chronic injury produce opposite effects on sensibility and responsiveness of tactile (desensitization) and nociceptive (sensitization) mechano-sensory afferents and the abnormal response of these afferents are critical to the maintenance of the neuropathic state and its recovery after nerve injury. Our published and preliminary data suggest that oxytocin (OXT) may speed recovery from pain after injury by returning peripheral input to normal. These data suggest that OXT may be used as a disease- modifying treatment after traumatic injury. With a base on the strength of our preliminary results, we anticipate that this research will contribute to understanding the role of OXT in the modulation of both normal and abnormal peripheral inputs, how this modulation may affect the recovery after nerve damage (L5 SNL), driving central circuitry, nocifensive behavior and attention (Project 2). We also expect to provide information on these afferents physiological properties and OXT mediated modulation to guide a detailed translational study to be implemented in human patients (Project 3).

PI_NAMEs: BOADA, MARIO DANILO (contact)

PROJECT_TERMS: Acute;Acute Pain;Address;Affect;Animal Behavior;Animals;Attention;Automobile Driving;base;Behavior;Behavioral;Central Nervous System;Chronic;Data;desensitization;Development;Disease;Dose;Drug Kinetics;electrical property;Exposure to;Fiber;Goals;Hour;Human;Hypersensitivity;Infusion procedures;injured;Injury;Intravenous infusion procedures;Joints;Ligation;Maintenance;mechanical stimulus;Mechanics;Mechanoreceptors;Mediating;Modification;Nerve Block;nerve damage;nerve injury;Nervous System;Neurobiology;Neurons;Neuropathy;neurophysiology;neurotransmission;Nociception;Nociceptors;Operative Surgical Procedures;Oxytocin;Pain;pain chronification;Pain management;pain reduction;pain relief;Patients;Peripheral;Peripheral Nerves;Persistent pain;pharmacodynamic model;Pharmacodynamics;Pharmacology;Phenotype;Physiological;Placebos;Plasma;Postoperative Pain;Process;Property;Prophylactic treatment;Publishing;Rattus;receptive field;Recovery;Research;Resolution;response;response to injury;Role;Sensory;sensory input;Site;Speed;Spinal Cord;Spinal nerve structure;Stimulus;synergism;Tactile;Testing;Time;translational study;Trauma;Traumatic injury;treatment optimization;Work

PROJECT_TITLE: Oxytocin-mediated modulation of peripheral mechanical sensibility after injury


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Clinical Research;Comparative Effectiveness Research;Health Services;Mental Health;Prevention;Suicide;Suicide Prevention

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

PHR: Project Narrative Scientific advances in addressing the rising suicide rate in the U.S. will require high-level interdisciplinary research that takes advantage of the increasing availability of big data to investigate the comparative effectiveness of alternative interventions prior to carrying out expensive and time-consuming large-scale controlled treatment trials or community interventions. The next generation of suicide prevention researchers will need to be comfortable using the advanced designs and analysis methods of comparative effectiveness research (CER) and appreciate the importance of addressing under-represented populations and recognizing the role played by health disparities in suicides and SRBs in order to address the rising U.S. suicide rate. We aim for our proposed Training Program in Comparative Effectiveness Research for Suicide Prevention to advance these goals by bringing together and cross training a talented group of epidemiologists and clinical predocs and postdocs who will become the vanguard of a new generation of sophisticated CER suicide prevention researchers.

PI_NAMEs: HERNAN, MIGUEL  (contact);NOCK, MATTHEW K;WANG, PHILIP S

PROGRAM_OFFICER_NAME: SIMS, BELINDA ENITA

PROJECT_TERMS: Comparative Effectiveness Research;Suicide prevention;Training Programs


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics;HIV/AIDS;Human Fetal Tissue;Immunotherapy;Infectious Diseases

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative CAR T cells have emerged as a promising cell therapy to enhance anti-HIV immunity and eliminate latently HIV-infected cells when combined with HIV latency reversal in a ‘kick and kill’ cure approach. However, CAR T cells are affected by immune exhaustion and the most effective latency reversal agents are associated with drug side-effects, including generalized immune activation. Our proposed study aims to investigate the mechanisms and therapeutic potential of autophagy inducers to enhance anti-HIV CAR-T cell function while reducing the toxicity of latency reversal agents.

PI_NAMEs: MARSDEN, MATTHEW DAVID;ZHEN, ANJIE  (contact)

PROGRAM_OFFICER_NAME: ZHOU, YAN

PROJECT_TERMS: adaptive immunity;Affect;Antigen Presentation Pathway;antiretroviral therapy;Autophagocytosis;bryostatin;CAR T cell therapy;CD8-Positive T-Lymphocytes;Cell Physiology;Cell Therapy;Cells;Cellular biology;Cellular immunotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;Chronic;Cytotoxic T-Lymphocytes;Data;Development;Disease remission;Drug Side Effects;Effectiveness;Engineering;Engraftment;exhaust;exhaustion;functional restoration;Genetic Transcription;Goals;Hematopoietic stem cells;HIV;HIV Infections;HIV-1;Homeostasis;humanized mouse;Immune;immune activation;Immune System Diseases;Immunity;Immunologic Surveillance;Immunotherapy;improved;In Vitro;in vitro activity;in vivo;Infection;Inflammation;Inflammatory;inhibitor;insight;Interferons;Lymphocyte;Maintenance;Malignant Neoplasms;Mediating;Memory;Metabolic;metabolic fitness;Metabolic Pathway;Metabolism;Methods;Mitochondria;mouse model;nonhuman primate;novel strategies;Organelles;Peripheral;Play;prevent;Production;reactivation from latency;Recrudescences;Regulation;Reporting;Research;response;Role;Safety;Signal Pathway;Signal Transduction;Sirolimus;Spermidine;success;T cell differentiation;T memory cell;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Toxic effect;trafficking;transcriptome sequencing;treatment effect;Viral;Viral Load result;viral rebound;Withdrawal

PROJECT_TITLE: Induction of autophagy to enhance CAR-T cells in HIV cure approaches

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Chronic Pain;Neurosciences;Pain Research;Physical Injury - Accidents and Adverse Effects

PHR: Oxytocin has been shown to be analgesic under some circumstances in preclinical animal models, however most of these studies use dose-to-effect strategies and simple reflexive behavioral measures. In this project, we model oxytocin pharmacokinetics in rats and use targeted concentration infusion paradigms to determine the effects of oxytocin in complex behaviors modified by peripheral nerve injury. We also modulate endogenous oxytocin circuits using a transgenic rat that expresses Cre recombinase selectively in oxytocinergic neurons. Together with similar studies assessing the effects of oxytocin on primary sensory afferents in rats and humans, and on human oxytocin pharmacokinetics and primary afferent physiology in the program project grant, these studies will provide evidence for or against an important role for oxytocin in promoting recovery from injury and mitigation of chronic pain.

PROJECT_TERMS: Ablation;Affective;affective disturbance;Amygdaloid structure;Analgesics;Anesthesia procedures;Animal Model;Animals;antagonist;antinociception;Attention;awake;Behavior;behavior measurement;Behavioral;behavioral study;Blood;Bolus Infusion;Brain;CASP3 gene;chronic pain;Clinic;Cognitive;Complex;Computers;Data;design;Disease;dorsal horn;Dose;Drug Kinetics;efficacy evaluation;Engineering;Enterobacteria phage P1 Cre recombinase;experimental study;Exposure to;Female;Fright;Human;Impaired cognition;Impairment;Infusion procedures;Injections;Injury;injury recovery;innovation;Knowledge;Literature;male;Methods;midbrain central gray substance;Modality;Modeling;Movement;Mutate;nerve injury;Nervous System;Neurons;Nociception;novel;Outcome Measure;Oxytocin;Oxytocin Receptor;Pain;pain behavior;pain chronification;Pain management;Pathway interactions;Penetrance;Perioperative;Peripheral;Peripheral nerve injury;Persistent pain;pharmacokinetic model;Physiology;Plasma;pre-clinical;Program Research Project Grants;Rat Transgene;Rattus;Recovery;Resolution;response;Rodent;Role;Route;Sensory;Signal Transduction;Spinal;Spinal nerve structure;Surface;Testing;Time;Translating;Trauma;Viral

PROJECT_TITLE: Central oxytocin mechanisms of pain recovery following nerve injury


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE The Medicare Advantage (MA) program serves a growing number of Black and Hispanic beneficiaries, but evidence about the quality and equity of care in MA compared to the traditional Medicare (TM) program is limited. This study will use national MA encounter (i.e., utilization) and survey data, including a new national survey of Medicare beneficiaries, to examine racial/ethnic disparities in care between the MA and TM programs and among MA plans, and to assess patients’ experiences of equity and trust in Medicare plans and providers. This work will illuminate opportunities for the MA program to improve care for racial/ethnic minorities and for policymakers to explicitly incorporate equity into assessments of MA plan performance, with the objective of reducing racial/ethnic disparities in care among Medicare beneficiaries.

PI_NAMEs: ROBERTS, ERIC T;TIPIRNENI, RENUKA  (contact)

PROGRAM_OFFICER_NAME: CHATTERJI, MINKI

PROJECT_TERMS: 10 year old;access disparities;Address;Adult;Advisory Committees;Affect;beneficiary;Black Populations;Black race;care coordination;Caring;cognitive interview;cost;Cost Control;Cost Sharing;Data;Dental;design;Dimensions;Discrimination;Disease;Disparity;Disparity population;disparity reduction;Drug Prescriptions;Enrollment;Equity;ethnic disparity;ethnic health disparity;ethnic minority;Ethnic Origin;experience;Future;Growth;Health;health care disparity;Health Personnel;health plan;Health Services Accessibility;Health system;Healthcare;Hispanic;Hispanic Populations;Hospitalization;improved;Incentives;Inequity;Insurance Carriers;Link;Managed Care;Measures;Medical;Medicare;Modeling;older adult;Patients;payment;Perception;Performance;Policies;Policy Maker;Population;Privatization;Process Measure;programs;Provider;provider networks;Publications;Quality of Care;racial difference;racial disparity;racial minority;Reporting;Risk Adjustment;Sampling;satisfaction;screening;Services;Source;Surveys;Testing;tool;Trust;United States National Institutes of Health;Variant;Vision;Work

PROJECT_TITLE: Racial/Ethnic Disparities in Medicare Advantage vs. Traditional Medicare: Evidence to Improve Equity in Medicare

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Pain Research

PHR: Narrative  Physical injury, including surgery, can cause chronic pain, but this is less likely around the time of childbirth, and initial work suggests this is due to a protective effect of the neurohormone, oxytocin. This project within the P01 will translate recent observations and laboratory work in the other projects to people. We will determine how oxytocin is distributed in the brain and the periphery after intravenous injection and use this to test how and at what sites it alters perceptions of light touch, vibration, and pain from pressure or heat or cold. We will finish with studies with intranasal self- administered oxytocin to apply the findings and prepare for clinical trials in the future.

PI_NAMEs: EISENACH, JAMES  (contact)

PROJECT_TERMS: absorption;Acute;Acute Pain;Affect;Affective;Age;Animals;appropriate dose;Area;Arthritis;Biological;Biological Assay;Biological Markers;Brain;Central Nervous System;Central Nervous System Agents;Childbirth;Chronic disability;chronic pain;Clinic;Clinical;clinical pain;Clinical Research;Clinical Trials;cognitive neuroscience;Complex;Contracts;Controlled Clinical Trials;Cross-Over Studies;Data;desensitization;Diameter;Dimensions;Discipline of obstetrics;Disease;Dose;Double-Blind Method;Drug Kinetics;Eligibility Determination;Enzyme-Linked Immunosorbent Assay;Ethnic Origin;experimental study;Fiber;Foundations;Frequencies;Functional disorder;Funding;Future;Grant;heat stimulus;Human;individual patient;Injury;injury recovery;International;Intranasal Administration;Intravenous infusion procedures;intravenous injection;Knee;knee replacement arthroplasty;Knowledge;Laboratories;Light;liquid chromatography mass spectrometry;Maps;Measures;Mechanoreceptors;men;Methods;Modeling;Nerve;Nervous System;Nervous System Disorder;Neurohormones;Nociception;Nociceptors;novel;Operative Surgical Procedures;Outcome Measure;Oxytocin;Pain;pain reduction;pain relief;Pathology;Patients;Penetration;Perception;Peripheral;Persons;pharmacodynamic model;Pharmacodynamics;pharmacokinetic model;Pharmacology;Placebo Control;Plasma;postoperative recovery;pre-clinical;Pregnant Uterus;pressure;Productivity;protective effect;Protocols documentation;Psychophysics;Pupil;Race;Randomized;Recovery;Reporting;Research;Rodent;Route;Self Administration;Sensory;Series;sex;simulation;Site;social neuroscience;Speed;Stimulus;Sweden;Testing;Time;tool;Touch sensation;Translating;Validation;vibration;volunteer;Weight;Woman;Work

PROJECT_TITLE: Creating PK/PD models for oxytocin action in humans and bridging to intranasal delivery


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Hematology;Infectious Diseases;Lung;Neurosciences;Rare Diseases;Sepsis

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Project Narrative Sepsis and acute respiratory distress syndrome (ARDS) are both life-threatening disorders; the former caused by a dysregulated host immune response to infection and the latter a severe form of acute lung injury that may be non-infectious in etiology. In our animal models, neuro- inflammation develops in both conditions, and this alters ventilatory patterns. We propose to map changes in the respiratory network activity and brainstem neuro-inflammation due to septic and sterile injuries and test whether these changes can be reversed by central anti-inflammatory therapies.

PI_NAMEs: JACONO, FRANK JOSEPH (contact)

PROGRAM_OFFICER_NAME: LAPOSKY, AARON D

PROJECT_TERMS: 3-Dimensional;Acute Lung Injury;Address;Affect;Anatomy;Animal Model;Anti-Inflammatory Agents;Appearance;Atlases;Attenuated;attenuation;Australia;awake;Biometry;Bleomycin;Brain;Brain Stem;Central Nervous System;clinically relevant;Collaborations;Coupling;COVID-19;Critical Care;cytokine;Data;Disease;Electrophysiology (science);Escherichia coli;Etiology;Feedback;Frequencies;Goals;Homeostasis;Immune response;Immunohistochemistry;improved;In Situ;Infection;Inflammasome;Inflammation;Inflammation Mediators;Inflammatory;Injury;innovation;insight;Interleukin-1 beta;Interleukin-6;International;Intervention;Life;Link;Lipopolysaccharides;Lung;lung injury;Magnetic Resonance Imaging;Maps;Measures;Medicine;Microinjections;Modeling;Molecular;Motor;multi-electrode arrays;multidisciplinary;multimodal data;Nerve;neural network;neuroinflammation;Neuronal Dysfunction;neuroregulation;Organ;Pathology;Pattern;Pattern Formation;Peripheral;Peritonitis;Preparation;prevent;Process;Publishing;Rattus;Reflex action;Regulation;Research Personnel;Respiration;respiratory;response;Science;Sensory;sensory feedback;sensory input;Sepsis;sepsis induced ARDS;septic;Silicon;Sleep;Sprague-Dawley Rats;Sterility;Stimulus;Synapses;Systemic infection;systemic inflammatory response;targeted treatment;Techniques;Technology;Testing;tocilizumab;Universities

PROJECT_TITLE: Neuroinflammation Maladapts Cardio Respiratory Circuits and Patterns

STUDY_SECTION: RIBT

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


NIH_SPENDING_CATS: Cancer;Immunotherapy;Skin Cancer

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Therapeutic antibodies targeting the immune checkpoint glycoprotein, Tim-3, on tumor-infiltrating T- lymphocytes promote immune-mediated tumor cell killing and have thus entered cancer clinical trials. We found that Tim-3 monoclonals also inhibit antigen-presenting cell (APC)- and melanoma cell-expressed Tim-3, the latter of which precariously induces tumor-intrinsic growth and antagonizes benefit of T-cell-directed Tim-3 therapy. This research seeks to optimize Tim-3 treatment modalities by accentuating desired T-cell or APC- mediated immunity, while avoiding undesired effects of melanoma-Tim-3 blockade through cell type-directed targeting of Tim-3 glyco-epitopes and/or signaling pathways.

PI_NAMEs: BARTHEL, STEVEN RUSSELL (contact);SCHATTON, TOBIAS

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: Affinity;antagonist;anti-cancer;Antibodies;Antibody Affinity;Antibody Response;Antibody Therapy;anticancer activity;Antigen-Presenting Cells;Binding;Biological Markers;Biological Models;Blocking Antibodies;cancer cell;cancer clinical trial;Cancer Patient;cell killing;Cell Lineage;cell type;Cells;Cellular Immunity;Charge;Clinical;clinical effect;clinical predictors;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;Disparity;efficacy validation;Epitopes;Evaluation;Glycoproteins;glycosylation;Growth;Human;Immune;immune checkpoint;immune checkpoint blockade;Immune checkpoint inhibitor;Immune Targeting;Immunity;Immunobiology;immunogenicity;Immunoglobulins;Immunooncology;Immunotherapy;Impairment;improved outcome;Infiltration;inhibitor;Investigation;knock-down;Lectin;Ligands;Link;Macrophage;Malignant Neoplasms;MAP Kinase Gene;Mass Spectrum Analysis;Mediating;Mediator;Melanoma;Melanoma Cell;Membrane;Metastatic Melanoma;Modality;Modeling;Modification;Mucins;Mus;mutant;Natural Killer Cells;Neoplasm Metastasis;neoplastic cell;next generation;novel;oncology trial;Outcome;Pathway interactions;Patients;Phosphorylation;Polysaccharides;potential biomarker;pre-clinical;predict clinical outcome;Proteins;Regimen;Research;response;RNA Interference;Sialic Acids;Signal Pathway;Signal Transduction;T-Lymphocyte;Therapeutic;Therapeutic antibodies;Therapeutic Trials;Tissues;Treatment Efficacy;Treatment outcome;tumor;tumor growth;Tumor Immunity;tumorigenesis;Variant;Western Blotting

PROJECT_TITLE: Cell type-directed Tim-3 targeting in melanoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-D(08)F]


ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: Project Narrative: This study centers cell movements called convergent extension which are controlled by a set of proteins called the planar cell polarity (PCP) proteins. These experiments will be significant because convergent extension is essential for neural tube closure and limb morphogenesis, and failure of these movements results in a human birth defects such as neural tube defects and skeletal dysplasia. Thus, experiments proposed here will shed new light on mechanisms underlying human congenital anomalies.

PI_NAMEs: WALLINGFORD, JOHN B (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Actins;Actomyosin;Adhesions;Animals;Award;Behavior;Biological;Biological Process;C cadherin;Cadherins;Cell Adhesion;cell behavior;cell motility;Cell Polarity;cell type;Cell-Cell Adhesion;Cells;Cellular biology;cofilin;Collaborations;Congenital Abnormality;congenital anomaly;convergent extension;Cytoskeleton;Defect;Development;Developmental Biology;Etiology;experimental study;Failure;Genetic;genetic regulatory protein;Goals;Human;Image;in vivo;in vivo imaging;insight;Integral Membrane Protein;Limb structure;Link;Mediating;Morphogenesis;Movement;Neural Tube Closure;Neural Tube Defects;Organ;Pattern;planar cell polarity;protein protein interaction;Proteins;Proteomics;Set protein;Signal Transduction;skeletal dysplasia;Speed;success;superresolution imaging;System;Time;Tissues;UPK3 gene;Vertebrates;Work

PROJECT_TITLE: Control of collective cell movement by planar cell polarity signaling

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


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);Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Prevention;Primary Health Care;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: Aurora

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Computational speech analysis (CSA) has shown promise as a cost-effective, rapid screening for patients with neurocognitive disorders (NCDs) by objectively and automatically quantifying speech and language use; however, critical steps must be taken before these measures can become clinically useful. I have training and experience in the neurology of speech and language, but require additional training in computational linguistics and paralinguistics, longitudinal markers of disease including neuroimaging and neuropsychological measures, and design of novel technology for dissemination in order to bring CSA into clinical practice. In this project, we propose to investigate the utility of using CSA measures in two distinct patient groups, including a highly characterized group of research participants that includes healthy controls, Alzheimer's disease patients, and mild cognitive impairment patients (Group A), and a group of consented clinic patients with different NCDs (Group B) and to follow these two groups in prospective, longitudinal studies to correlate spontaneous speech measures with standardized linguistic, neuropsychological, and biological measures.

PI_NAMEs: PRESSMAN, PETER SCOTT (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Accent;accurate diagnosis;Address;Adult;Advisory Committees;aging population;Algorithms;Alzheimer disease screening;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease pathology;Alzheimer's disease patient;Area;Biological;brain magnetic resonance imaging;career development;Caregivers;Characteristics;Classification;Clinic;Clinical;clinical application;clinical practice;Clinical Trials;Cognitive;cohort;Communities;Computational Linguistics;Computers;Consent;cost effective;Cross-Sectional Studies;Dementia;Dementia with Lewy Bodies;design;Development;Development Plans;Diagnosis;Diagnostic;diagnostic biomarker;Diagnostic Procedure;Diagnostic Sensitivity;diagnostic tool;Disease;Disease Marker;Early Diagnosis;Effectiveness;Enrollment;Ensure;Ethics;Evaluation;experience;Fostering;Frontotemporal Dementia;Goals;healthy aging;Image;imaging biomarker;Impaired cognition;Impairment;improved;Individual;Intuition;Investigation;Knowledge;Language;Language Tests;Linguistics;Liquid substance;Longitudinal Studies;longitudinal, prospective study;Machine Learning;machine learning algorithm;Measures;Memory;Mentorship;mild cognitive impairment;morphometry;Neuroanatomy;Neurocognitive;neurocognitive disorder;neuroimaging;Neurology;neuropsychiatry;Neuropsychological Tests;Neuropsychology;new technology;novel;novel diagnostics;novel therapeutics;Outcome;Participant;patient screening;Patients;Performance;Population;Positioning Attribute;Preparation;Prevalence;Primary Care;primary care provider;primary outcome;prospective;Qualifying;Quality of life;Rapid screening;recruit;Reproducibility;Research;screening;Screening procedure;skills;Speech;Standardization;success;Techniques;Technology;technology development;Testing;Time;tool;Training;trait;Variant

PROJECT_TITLE: Computational Speech Analysis in Alzheimer's Disease and Other Neurocognitive Disorders

STUDY_SECTION_NAME: Basic Neuroscience of Aging Study Section[NIA-N]


ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Project Narrative The IL-17 family of inflammatory cytokines plays important roles in the development of colorectal cancer (CRC). This project aims to uncover how IL-17 inhibits anti-inflammatory regulatory T cells to limit tumorigenesis in the colon. These studies will thus provide novel insights into how the IL-17-Treg circuit might be targeted to prevent or treat CRC.

PI_NAMEs: WANG, KEPENG  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Ablation;Acceleration;adaptive immunity;Adjuvant;Adoptive Transfer;Affect;Anti-Inflammatory Agents;Antibodies;anticancer activity;Autoimmunity;B-Lymphocytes;Bacterial Infections;cancer immunotherapy;cancer initiation;cancer prevention;CCR6 gene;CD8B1 gene;Cell Communication;cell motility;Cell Physiology;Cell Survival;Cells;Cellular biology;chemokine;Colon;colon tumorigenesis;Colonic Neoplasms;Colorectal Cancer;colorectal cancer treatment;Colorectal Neoplasms;CXC chemokine receptor 3;CXCL9 gene;CXCR3 gene;cytokine;design;Development;Environment;Epithelial Cells;Family;Family member;Fibroblasts;FOXP3 gene;Gene Expression;Genetic Transcription;Glucose;Glycolysis;Human;IL17 gene;IL2RA gene;Immune;Immune Cell Suppression;Immunologic Surveillance;Immunosuppression;Immunotherapy;improved;Infiltration;Inflammation;Inflammatory;insight;Interleukin-1 beta;Interleukin-10;interleukin-17C;Interleukin-2;Interleukin-6;invention;Investigation;Knowledge;Malignant Neoplasms;Mediating;Membrane;migration;Molecular;mouse model;Mus;mutant;Myeloid Cells;neoplastic cell;neutrophil;novel;novel therapeutics;PDPK1 gene;Phase;phosphoinositide-3,4,5-triphosphate;PIK3CG gene;Play;Predisposition;prevent;Prevention strategy;Production;Proliferating;receptor;recruit;Regulation;Regulatory T-Lymphocyte;Reporting;Role;Signal Pathway;Signal Transduction;Site;Specimen;Stat5 protein;T-Lymphocyte;Testing;Transforming Growth Factor beta;Treatment outcome;treatment strategy;tumor;Tumor Immunity;tumor microenvironment;tumorigenesis;Work

PROJECT_TITLE: Control of regulatory T cells by IL-17 in colorectal cancer

STUDY_SECTION: TTT

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