NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biotechnology;Brain Disorders;Dementia;Depression;Mental Health;Microbiome;Neurodegenerative;Neurosciences

ORG_CITY: ATHENS

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Narrative:  Signaling networks deficient in monoamine neurotransmitters have been linked to the onset and progression of intellectual deficits in Alzheimer's disease (AD). Thus restoring norepinephrine and dopamine inputs represents an effective approach to alleviating AD's cognitive and behavioral symptoms and could delay disease onset. Dopamine replacement therapy with the dopamine precursor L-DOPA remains the most effective treatment for restoring DA/NE inputs in humans. However, the L-DOPA oral tablet's pulsatile delivery is often associated with severe adverse effects after long-term use. Thus, the main goal of this proposal is to develop and optimize a novel therapeutic platform of live biological L-DOPA delivery to restore monoamine neurotransmitters to steady-state levels that relieve symptoms of ADRD without adverse effects.

PI_NAMEs: KANTHASAMY, ANUMANTHA GOUNDER (contact);PHILLIPS, JAMES GREGORY

PROJECT_TERMS: Ablation;Address;Adverse effects;Affect;Agitation;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Amyloid beta-Protein;Animal Disease Models;Animal Model;Animal Testing;Anxiety;Bacteria;Behavioral;Behavioral Symptoms;Biological;Biological Assay;Biological Response Modifier Therapy;Biomedical Engineering;Brain;canine model;Canis familiaris;Carbidopa;Cerebrum;cholinergic;Chromosomes;Chronic;Clinical;Cognitive;Data;Dementia;Disease;Disease Progression;Dopamine;Dopamine Agonists;dopamine replacement therapy;Dopamine Uptake Inhibitors;Dose;drug development;Drug Kinetics;effective therapy;efficacy evaluation;efficacy study;Emotional;Engineered Probiotics;Engineering;Escherichia coli;Evaluation;Executive Dysfunction;FDA approved;Financial Hardship;Flavin-Adenine Dinucleotide;Frequencies;gastrointestinal;Genes;Genetic Engineering;Glutamates;Goals;gut colonization;gut health;gut microbiome;Human;Impaired cognition;improved;In Vitro;in vitro testing;in vivo;in vivo Model;ineffective therapies;Inflammation;irritation;L-DOPA induced dyskinesia;Lead;lead optimization;Legal patent;Link;locus ceruleus structure;Medical;Memory;Mental Depression;Microbial Genetics;microbiome;mild cognitive impairment;Mixed Function Oxygenases;Modality;monoamine;mortality;Motivation;mouse model;Mus;neural circuit;neurobehavioral;Neurobehavioral Manifestations;neurochemistry;Neurodegenerative Disorders;Neurofibrillary Tangles;neuroinflammation;neuron loss;Neurons;Neuropsychology;neurotransmission;Neurotransmitters;Norepinephrine;novel;novel therapeutic intervention;novel therapeutics;Onset of illness;Oral;Oral Administration;Outcome;Oxidoreductase;Pathology;Patients;Pharmaceutical Preparations;Pharmacodynamics;Plasma;Play;pre-clinical;preclinical efficacy;Probiotics;Production;programs;promoter;Property;reduce symptoms;Regulatory Element;resilience;Rhamnose;Ritalin;Rodent;Rodent Model;Role;Safety;Senile Plaques;side effect;Signal Transduction;small molecule;social;Societies;standard care;Standardization;sugar;symptom treatment;Symptoms;Synapses;System;Tablets;targeted treatment;tau Proteins;tau-1;Testing;Therapeutic;therapeutic biomarker;Toxicology;Transgenic Organisms;translational approach;Treatment Efficacy;Ventral Tegmental Area

PROJECT_TITLE: Novel Reengineered Microbiome-based Biologic Therapy to Treat Cognitive and Behavioral Symptoms of Alzheimer's Disease and Related Dementias


ADMINISTERING_IC: HG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_DEPT: GENETICS

ORG_FIPS: US

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: NARRATIVE Genetic variation can offer powerful clues about the biological basis of disease. Human genomes vary at scales large and small; while fine-scale (single-nucleotide) DNA variation is readily recognized by today’s analysis methods, many kinds of complex, larger-scale variation have been challenging to recognize and analyze. The goal of our work is to develop new, powerful ways to combine many kinds of genome analysis data to (i) understand how human genomes vary at these larger scales among many thousands of people; and (ii) identify many ways that genetic variation shapes human biology and risk of disease.

PI_NAMEs: MCCARROLL, STEVEN ANDREW (contact)

PROGRAM_OFFICER_NAME: ARGUELLO, ALEXANDER

PROJECT_TERMS: Alleles;biobank;Biological;Blood;Cholesterol;Code;Collection;Companions;Complex;Computer software;Copy Number Polymorphism;Data;Data Analyses;Data Set;Disease;disorder risk;DNA;DNA Sequence;exome;Exons;Gene Combinations;Gene Conversion;Gene Dosage;Gene Frequency;Gene Proteins;Genes;genetic analysis;genetic approach;genetic association;Genetic Polymorphism;Genetic study;Genetic Variation;Genome;genome analysis;genome wide association study;Genotype;Goals;Haplotypes;Homologous Gene;homologous recombination;Human;Human Biology;Human Genetics;Human Genome;innovation;Lupus;Maps;Methods;Minisatellite Repeats;Mutation;novel;Nucleotides;Pattern;Persons;Phase;Phenotype;phenotypic data;Population;Property;protein structure;Regulatory Element;Research;schizophrenia risk;Scientist;Series;Shapes;Sjogren's Syndrome;SNP array;Structure;Tertiary Protein Structure;Testing;trait;Variant;whole genome;Work

PROJECT_TITLE: Structurally complex genome loci in human populations and human phenotypes

STUDY_SECTION: GCAT

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


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative More than 40% of the US population is projected to suffer from some form of cardiovascular disease within the next decade. This creates a pressing need for novel scientific approaches that can identify therapeutic targets in the intricate cascades that facilitate diseased states of the heart. The studies outlined in this grant application seek to engineer, validate and use optogenetic proteins to better define the specific signaling players of cardiac hypertrophy.

PI_NAMEs: HAAR, LAUREN L (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Action Potentials;Address;Adenylate Cyclase;analog;Applications Grants;Behavior;Behavior Control;Biochemical;Biochemical Pathway;biological adaptation to stress;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular system;Categories;cell behavior;Cell membrane;cell type;Cells;Communication;Complex;coronary fibrosis;Coupling;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Cytoskeleton;Data;Deposition;design;Development;Dimensions;Disease;Engineering;Event;extracellular;Extracellular Matrix;Failure;Fetal Growth;Fibroblasts;Fibrosis;Generations;Genes;Heart;Heart failure;Heart Hypertrophy;Homeostasis;Hypertrophy;Individual;intercellular communication;interest;Ion Channel Gating;Light;light gated;Location;Lower Organism;Maps;Measures;Mediating;Mitochondria;Myocardial;Nature;neural circuit;Neurons;Neurosciences;novel;optogenetics;Organ;Pathologic;Pathway interactions;Physiological;Play;Population;Production;programs;Proliferating;Protein Engineering;Protein Isoforms;Protein Kinase;Protein Kinase C;Proteins;Research;Resolution;response;Role;Sarcoplasmic Reticulum;Series;Signal Pathway;Signal Transduction;Signaling Protein;Site;spatiotemporal;Stimulus;Stress;Technology;therapeutic target;Tissue-Specific Gene Expression;tool;Validation;Work;Workload

PROJECT_TITLE: Optogenetic protein design for hypertrophic signaling pathways

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dietary Supplements;Microbiome;Natural Products;Nutrition;Prevention;Prostate Cancer;Urologic Diseases

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: Project Narrative Currently, there is a paucity of research that systematically examines agents for chemoprevention men on active surveillance (AS) for prostate cancer (PCa). Several epidemiological, in vitro, preclinical and early phase trials completed by our team and others have shown that the green tea catechins (GTC) are potent inhibitors of PCa carcinogenesis through multiple mechanisms, bioavailable in tissue and plasma, reduces several intermediate biomarkers implicated in PCa progression and without toxicities at these doses. Based on the available evidence, we hypothesize that men with biopsy proven adenocarcinoma of the prostate who meet the criteria for AS, who receive GTC at a dose of 800 mg EGCG per day (vs. placebo) for 24 months, will have a significantly decreased rate of clinical progression. We will test this hypothesis using a rigorous experimental design in a phase II, randomized clinical trial to evaluate the bioavailability, safety, effectiveness and mechanism by which GTC prevents clinical progression of disease in men on AS for PCa. Results of the proposed study may inform development of a phase III clinical trial and ultimately provide a strategy for chemoprevention with GTC in men on AS.

PI_NAMEs: KUMAR, NAGI B. (contact)

PROGRAM_OFFICER_NAME: PARNES, HOWARD L

PROJECT_TERMS: 5 Alpha-Reductase Inhibitor;Adherence;Adoption;Adverse event;Anxiety;Apoptosis;Biodistribution;Biological;Biological Availability;Biological Markers;Biopsy;cancer chemoprevention;carcinogenesis;CASP3 gene;Cell Survival;Cessation of life;Characteristics;Chemoprevention;Chemopreventive Agent;Classification;Clinical;Clinical Trials;Conflict (Psychology);Core Biopsy;cyclin-dependent kinase inhibitor 1B;density;design;Detection;Development;Dietary History;Disease;Disease Progression;Dose;Double-Blind Method;Dutasteride;early phase trial;Effectiveness;Eligibility Determination;epicatechin;epicatechin gallate;Epidemiology;Epigallocatechin Gallate;Evaluation;Experimental Designs;Exposure to;Finasteride;Formulation;Future;gallocatechol;Gene Expression;Genetic Markers;Gleason Grade for Prostate Cancer;Green tea;gut microbiome;Histologic;I Kappa B-Alpha;In Vitro;Incidence;indexing;Induction of Apoptosis;inhibitor;Intervention;Kinetics;Life Style;lower urinary tract symptoms;Magnetic Resonance Imaging;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;men;Mental Depression;metabolomics;metatranscriptomics;microbiota;Molecular;Monitor;Morbidity - disease rate;NF-kappa B;novel;oncotype;Outcome;overexpression;overtreatment;Pathway interactions;Patients;Pattern;Periodicals;personalized approach;pharmacologic;Phase;Phase II Clinical Trials;Phase III Clinical Trials;pill;Placebos;Plasma;post intervention;pre-clinical;prevent;Prevention strategy;preventive intervention;progression risk;Prostate Adenocarcinoma;prostate biopsy;prostate cancer cell;prostate cancer progression;prostate cancer risk;prostate carcinogenesis;Prostate-Specific Antigen;Proteasome Inhibition;Quality of life;Randomized;randomized, clinical trials;Recommendation;Regulation;Reporting;Research;Risk;Risk Reduction;Safety;Screening for Prostate Cancer;serum PSA;Signal Transduction;Standardization;stool sample;Subgroup;Testing;Therapeutic Intervention;Time;Tissues;Toxic effect;tumor;Uncertainty;Validation;Variant

PROJECT_TITLE: Phase II Clinical trial of GTC in Men on Active Surveillance

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


ADMINISTERING_IC: MH

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Mental Health;Neurosciences

ORG_CITY: PITTSBURGH

ORG_NAME: CARNEGIE-MELLON UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE An individual’s level of engagement with their environment, often described as arousal, is impaired in a variety of neurologic disorders, including schizophrenia and Alzheimer’s. Systemic metrics of arousal, such as heart rate and pupil diameter, could be used as non-invasive, diagnostic markers if the link between arousal and brain activity was understood. The proposed research investigates how neural activity and cerebral hemodynamics slowly fluctuate with arousal level, measured systemically, and in turn influence behavior.

PI_NAMEs: ISSAR, DEEPA  (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Affect;alertness;Alzheimer's Disease;Arousal;Attention;Attention Deficit Disorder;Auditory;Behavior;behavior influence;Behavioral;Biological Markers;biomarker identification;Blood Vessels;Brain;Brain Diseases;Brain region;Brain Stem;Cells;cerebral hemodynamics;Cerebrovascular system;circadian;Clinical;Cognition;Cognition Disorders;Cognitive;Cognitive deficits;cognitive function;cognitive task;Communities;Coupled;Cues;Detection;diagnostic biomarker;Diameter;Discrimination;Disease;Electroencephalography;Electrophysiology (science);Engineering;Environment;experimental study;Functional Magnetic Resonance Imaging;Global Change;Goals;Heart Rate;hemodynamics;Hour;Impairment;Individual;insight;Link;Macaca mulatta;Measures;Modality;Monkeys;multimodality;Near-Infrared Spectroscopy;Nervous System Disorder;neural;neuromechanism;Neurosciences;Optics;Performance;Perfusion;Physicians;Physiology;Population;Positioning Attribute;Prefrontal Cortex;Psychophysics;Pupil;Reaction Time;recruit;Reporting;Research;Rest;Scalp structure;Schizophrenia;Scientist;Short-Term Memory;Signal Transduction;skills;Stimulus;System;Terminology;Testing;Training;trend;Universities;Variant;Wakefulness;Work

PROJECT_TITLE: Internally and externally driven arousal changes in neural activity and hemodynamics


ADMINISTERING_IC: DA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

ORG_CITY: STANFORD

ORG_DEPT: PSYCHIATRY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: C-DIAS OVERALL: PROJECT NARRATIVE In this revised P50 proposal, we envision a Center for Dissemination and Implementation At Stanford: C-DIAS. Public access to (reach) and routine delivery of (adoption) evidence-based addiction treatments are historic and persistent problems. Serving as an open, national and enduring resource, this unique Center of Excellence will integrate broad-based multi-disciplinary expertise, creatively develop expert capacity, advance the science of implementation, and promote the equitable sustainment of proven addiction treatments.

PI_NAMEs: MCGOVERN, MARK P (contact)

PROGRAM_OFFICER_NAME: MARTIN, LINDSEY ANN

PROJECT_TERMS: Acceleration;addiction;Address;Adoption;Area;Communities;Consultations;contingency management;cost;County;Creativeness;data harmonization;Dedications;design;digital treatment;Disparity population;Dissemination and Implementation;dissemination science;Economic Models;Epidemic;Equity;evidence base;Evidence based treatment;Fellowship;Fostering;Funding;Geography;Goals;health care disparity;health economics;Health Policy;Health Services;Health Services Research;Health system;Healthcare Systems;human capital;implementation efforts;implementation evaluation;implementation research;implementation science;implementation strategy;improved;Individual;Intervention;Lead;Leadership;Link;Measures;Medicine;member;Mentorship;Methods;Modeling;multidisciplinary;National Institute of Drug Abuse;National Institute of Mental Health;online resource;opioid use disorder;Outcome;overdose death;Overdose reduction;Patients;pharmacologic;Phase;Policy Maker;Preparation;primary care clinic;Privatization;psychosocial;Public Health;Reaction;Research;Research Institute;Research Project Grants;Resources;scale up;service delivery;Services;Standardization;standardize measure;stimulant use;Strategic Planning;Substance Use Disorder;success;synergism;System;Techniques;tool;Training and Education;Translating;Translations;treatment program;treatment services;Variant

PROJECT_TITLE: Center for Dissemination and Implementation At Stanford (C-DIAS)


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);Substance Misuse

PROJECT_TERMS: Acceleration;Accountability;Active Learning;addiction;Advisory Committees;Advocacy;Advocate;Atmosphere;career development;career networking;certificate program;Chemistry;Collaborations;Communication;Communities;Consultations;cost effectiveness;Creativeness;Data;data sharing;Dedications;design;Dissemination and Implementation;dissemination science;Education;Educational workshop;Engineering;Ensure;Environment;Ethics;Evaluation;evidence base;experience;Faculty;Fostering;Foundations;Funding;Goals;Health system;Home;Housing;implementation research;implementation science;Individual;Influentials;innovation;Institution;interest;Investments;Knowledge;Knowledge acquisition;Lead;Leadership;Learning;lectures;Logistics;Measurable;member;Mentors;Mission;Monitor;multidisciplinary;National Institute of Drug Abuse;National Institute of Mental Health;open data;operation;organizational structure;Policies;Positioning Attribute;Process;Productivity;programs;promoter;Public Domains;Public Health;Publications;Qualifying;Quality Control;Research;Research Assistant;Research Institute;Research Personnel;Resource Sharing;Resources;response;Rewards;scale up;Science;Services;social media;symposium;synergism;Technology;technology platform;Thinness;tool;Training;Training and Education;treatment research;treatment services;United States National Institutes of Health;United States Substance Abuse and Mental Health Services Administration;user centered design;user-friendly;virtual;web portal;web site

PROJECT_TITLE: Center for Dissemination and Implementation At Stanford (C-DIAS): Administrative Core


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Comparative Effectiveness Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse

PI_NAMEs: SALDANA, LISA  (contact)

PROJECT_TERMS: Acceleration;access disparities;Acute;addiction;Address;Adoption;Behavior Therapy;Clinical;Communities;Community Health Systems;Community Practice;community setting;Complex;contextual factors;cost;COVID-19 pandemic;design;Disparity;disparity gap;Dissemination and Implementation;effective therapy;Effectiveness;effectiveness clinical trial;efficacy clinical trial;Ensure;Epidemic;Equity;ethnic minority;evidence base;Evidence based intervention;Evidence based practice;flexibility;Funding;Goals;Health Services Research;Healthcare Systems;implementation evaluation;implementation facilitation;implementation measures;implementation process;implementation research;implementation science;implementation strategy;Improve Access;improved;Individual;innovation;instrument;Intervention;Investments;Knowledge;Laboratory Research;Learning;marginalized population;Measures;member;Methodology;Methods;Modeling;Monitor;mortality;Motivation;multidisciplinary;National Institute of Drug Abuse;opioid use disorder;Outcome;Patients;Persons;pharmacologic;Pharmacological Treatment;Policies;Policy Maker;Positioning Attribute;Privatization;Process;psychosocial;racial minority;Research;Research Methodology;Research Project Grants;Resource-limited setting;Resources;response;routine care;scale up;Scientific Advances and Accomplishments;Scientist;Standardization;stimulant use disorder;Substance Use Disorder;support tools;System;Techniques;Time;tool;Translating;Underrepresented Populations;United States National Institutes of Health;Variant;Work

PROJECT_TITLE: Center for Dissemination and Implementation At Stanford (C-DIAS): Research Core


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Health Services;Palliative Care

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: PROJECT NARRATIVE The proposed research is consistent with the broader public health goals focused on improving disease self- management among patients with advanced or serious illness and the Centers for Medicare and Medicaid Services (CMS) call for increased patient engagement in advance care planning (ACP) as part of standard care. Specifically, the proposed study will address this critical public health issue by refining and pilot testing the Conversations Helpful for Awareness of Illness Trajectory (CHAT) intervention to improve communication about illness trajectory, and subsequently improve symptom burden and advance care planning, among patients with heart failure with preserved ejection fraction (HFpEF). Therefore, this study is aligned with the NIA’s long-term goals of improving the quality of care for patients with advanced illness and CMS’s goal of improving engagement in ACP.

PI_NAMEs: GOYAL, PARAG  (contact);SHEN, MEGAN JOHNSON

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: acceptability and feasibility;Address;Advance Care Planning;advanced disease;aging related;animation;Area;Awareness;Behavior;behavior change;Behavioral Model;Caregivers;Caring;Chronic;Communication;Communication Tools;Competence;Data;Decision Making;Disease;driving behavior;EFRAC;Elderly;Eligibility Determination;Enrollment;Feedback;Future;Goals;Health;health goals;health training;Healthcare;Heart;Heart failure;Hospitalization;Image;Impairment;implementation science;improved;innovation;Internist;Intervention;intervention refinement;Interview;Knowledge;Learning;Life;Malignant Neoplasms;Managed Care Programs;Medical;Methods;Modeling;Monitor;Nurses;older adult;Palliative Care;Participant;Patient Care;patient engagement;patient oriented;Patient Outcomes Assessments;patient population;Patients;Persons;Physician-Patient Relations;Physicians;pilot test;preservation;Primary Care Physician;primary outcome;Prognosis;psychologic;Public Health;Quality of Care;Quality of life;Randomized, Controlled Trials;Recommendation;Reporting;Research;Research Personnel;Scientist;Self Care;Self Determination;Self Efficacy;Self Management;social;Specialist;standard care;Structure;Survival Rate;Symptom Burden;symptom management;symptomatic improvement;Symptoms;Syndrome;System;Techniques;Telephone;Terminal Disease;Text;theories;Therapeutic Intervention;therapy development;tool;treatment arm;treatment as usual;United States Centers for Medicare and Medicaid Services;United States National Institutes of Health;Videoconferencing

PROJECT_TITLE: Advancing the Conversations Helpful for Awareness of Illness Trajectory (CHAT) Intervention

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Stimulant Use and Misuse;Substance Misuse

PI_NAMEs: BROWN, C. HENDRICKS (contact)

PROJECT_TERMS: Accident and Emergency department;addiction;Address;Adopted;Adoption;Affect;Behavior;Caring;Cessation of life;Communities;community research;Complex;contextual factors;contingency management;cost;Country;County;COVID-19 pandemic;Criminal Justice;Data;data harmonization;data integration;Decision Making;Decision Support Model;Decision Support Systems;design;Disparity;Dissemination and Implementation;effective therapy;epidemiologic data;Epidemiology;Equity;Evidence based intervention;Evidence based practice;experimental study;Failure;falls;Feedback;flexibility;Florida;Funding;Heart;Homelessness;Hospitalization;Human Resources;implementation context;implementation outcomes;implementation process;implementation strategy;improved;Individual;Influentials;innovation;Intervention;Interview;Knowledge;Learning;Local Government;Location;Measures;Mediation;medication for opioid use disorder;Methodology;Methods;Minority;Modeling;models and simulation;Monitor;mortality;novel therapeutics;open data;Opioid;opioid overdose;Outcome;Output;Overdose;overdose death;Overdose reduction;Persons;Phase;Policy Maker;Population;Process;programs;Public Health;Recommendation;Recovery;Research;Research Personnel;Research Project Grants;Resources;response;Risk;service providers;Services;simulation;Specific qualifier value;Standardization;standardize measure;Stimulant;Stimulant overdose;stimulant use disorder;substance use;support tools;Surface;Surveys;System;Testing;Time;tool;Training;trustworthiness;Universities;US State

PROJECT_TITLE: C-DIAS RP 1: A community-driven modeling approach for identifying and implementing evidence-based interventions and implementation strategies to reduce overdose deaths.


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Cancer;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Immunotherapy;Rare Diseases

ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: The lack of molecular mechanistic insights into the initiation and progression of oral squamous cell carcinoma has been the main hindrance in the development of new, directed therapy. HuR an RNA-binding protein that is overexpressed in oral cancers, post-transcriptionally control gene expression of epithelial and metabolic genes. The experiments described in this proposal will evaluate the biological properties of HuR and the contribution of cross-talk between oral epithelium and T-lymphocytes using a mouse model of oral tumorigenesis.

PI_NAMEs: MEHROTRA, SHIKHAR ;PALANISAMY, VISWANATHAN  (contact)

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: anti-tumor immune response;bench-to-bedside translation;Binding;Biological;Biology;carcinogenesis;CD8-Positive T-Lymphocytes;Cell Compartmentation;cell mediated immune response;Cell Separation;Cell Survival;Collaborations;Cues;cytokine;Data;Development;Disease;Down-Regulation;effector T cell;Elements;Embryo;Energy Metabolism;Epithelial Cells;Epithelium;Equilibrium;Eukaryota;Exhibits;experimental study;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene network;Genes;glucose metabolism;Glycolysis;Head and Neck Squamous Cell Carcinoma;Health;Homeostasis;Human;HuR protein;Hyperplasia;IL2RA gene;Immune;immune cell infiltrate;Immune response;Immunosuppression;Inflammation;Inflammatory;insight;Interferon Type II;Intervention Studies;Keratin;Knock-out;Knockout Mice;Laboratories;Lead;Lesion;LoxP-flanked allele;malignant mouth neoplasm;Mammalian Cell;Mass Spectrum Analysis;Mediating;Messenger RNA;Metabolic;Modeling;Molecular;mouse model;Mouth Neoplasms;mouth squamous cell carcinoma;Mus;neoplastic cell;Nitroquinolines;novel;Oral;oral cavity epithelium;oral tumorigenesis;Outcome;overexpression;Oxidative Phosphorylation;Oxides;Pathologic;Pharmaceutical Preparations;pharmacologic;Play;Positioning Attribute;Post-Transcriptional Regulation;prevent;Proliferating;Property;Proteins;Proteomics;Publishing;Pyrvinium pamoate;Regulator Genes;Regulatory T-Lymphocyte;Resistance;response;RNA;RNA-Binding Proteins;Role;small molecule;Spleen;Squamous cell carcinoma;T cell response;T-Lymphocyte;Testing;Therapeutic;Therapeutic Intervention;Tissues;TNF gene;transcriptome sequencing;transcriptomics;Transgenic Organisms;Translations;tumor;tumor growth;tumor immunology;tumor metabolism;tumor microenvironment;tumor progression;Tumor Tissue;tumorigenesis;Vision

PROJECT_TITLE: Intersections of RNA-binding proteins and T-cells in oral epithelial plasticity

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Machine Learning and Artificial Intelligence;Nutrition;Obesity;Precision Medicine;Prevention;Social Determinants of Health

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE This multidisciplinary effort aims to accelerate the discovery of gene-environment (GxE) interactions that influence colorectal cancer (CRC) risk. We will conduct functional-genomic guided genome-wide GxE scans in over 230,000 racially and ethnically diverse CRC cases and controls across the spectrum of environmental risk factors. This approach improves the statistical power and biological interpretability of GxE findings. Discoveries have high translational potential for precision prevention as they can guide lifestyle interventions as well as personalize screening decisions, ultimately, reducing the burden of CRC.

PI_NAMEs: GAUDERMAN, WILLIAM JAMES;PETERS, ULRIKE  (contact)

PROGRAM_OFFICER_NAME: MECHANIC, LEAH E

PROJECT_TERMS: Acceleration;Age;Age of Onset;Alcohols;Atlases;biobank;Biological;Biological Markers;Biological Process;Biopsy;C-reactive protein;Cancer Etiology;cell type;Cells;Cessation of life;Chromatin;Chromosome Mapping;Chronic;Clinical;Clinical Data;cohort;Colorectal;Colorectal Cancer;colorectal cancer prevention;colorectal cancer risk;Communities;Complex;computerized tools;Data;data integration;Data Set;Databases;deep learning;deep learning model;Development;Diabetes Mellitus;Diet;Dietary Factors;Disease;Drug usage;Environment;Environmental Exposure;Environmental Risk Factor;epidemiologic data;ethnic diversity;Ethnic Population;functional genomics;gene discovery;gene environment interaction;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic epidemiology;Genetic Risk;genetic risk factor;Genetic study;genetic variant;Genetic Variation;Genome;genome-wide;Genomics;Glucose;Guide prevention;high dimensionality;improved;Individual;individualized prevention;Inflammation;inflammatory marker;innovation;insight;instrument;Insulin;interest;Interleukin-6;Intervention;Life Style;lifestyle intervention;Link;Malignant Neoplasms;Measures;Metabolic;Methods;modifiable risk;Mucous Membrane;multidisciplinary;multimodality;Multiomic Data;multiple omics;novel;Obesity;Participant;personalized screening;predictive marker;preventive intervention;Process;racial diversity;racial population;Resources;Risk;Risk Factors;risk prediction;risk prediction model;risk variant;Sampling;Scanning;sex;single cell ATAC-seq;single cell technology;Smoking;Statistical Methods;Stress;study population;Technology;Testing;Tissues;Training;Transcriptional Regulation;Translating;translational potential;Translations;Tumor Subtype;Untranslated RNA;Variant

PROJECT_TITLE: An integrative omics approach to investigate gene-environment interaction in colorectal cancer risk

STUDY_SECTION: CHD

STUDY_SECTION_NAME: Cancer and Hematologic Disorders Study Section[CHD]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Comparative Effectiveness Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Services;Opioid Misuse and Addiction;Opioids;Stimulant Use and Misuse;Substance Misuse

PI_NAMEs: BECKER, SARA  (contact)

PROJECT_TERMS: Abstinence;addiction;Address;Adoption;Advisory Committees;Black Box;Cessation of life;Climate;Cocaine;cohort;Collaborations;Computerized Medical Record;contextual factors;contingency management;Data;Data Collection;data harmonization;design;Dissemination and Implementation;Drops;effective intervention;Effectiveness;effectiveness testing;effectiveness/implementation trial;Ensure;Equity;Evaluation;evidence base;Evidence based intervention;Evidence based treatment;Excision;experience;experimental study;Family;Feedback;follow up assessment;follow-up;Goals;high risk;HIV Infections;Human Resources;implementation context;implementation determinants;implementation outcomes;implementation science;implementation strategy;implementation/effectiveness;improved;Incentives;Individual;Interview;Laboratories;Leadership;Legal;Maintenance;Measures;Mediator;Medical;medical specialties;medication for opioid use disorder;Mentors;Methamphetamine;Methods;Modeling;New England;Opioid;opioid epidemic;opioid overdose;opioid treatment program;opioid use;opioid use disorder;Outcome;Overdose;overdose death;Patient-Focused Outcomes;Patients;Perception;Performance;Persons;Pharmaceutical Preparations;Phase;Population;Provider;psychostimulant;Public Health;Public Sector;Quality of Care;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;recruit;Reporting;Research;Research Project Grants;research to practice;Risk;Role;Science;Service provision;Services;Source;Specific qualifier value;standardize measure;Stimulant;stimulant dependence;stimulant use;Technology Transfer;Testing;Time;Training;treatment duration;treatment organization;treatment response;treatment services;United States Substance Abuse and Mental Health Services Administration;uptake;Vocation

PROJECT_TITLE: C-DIAS RP 2: Implementing contingency management for stimulant use in specialty addiction treatment organizations


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Telehealth

PI_NAMEs: GLASS, JOSEPH EDWIN (contact)

PROJECT_TERMS: addiction;Address;Adherence;Advisory Committees;African American;Asian Americans;Authorization documentation;Black American;brief intervention;Buprenorphine;Caring;Cellular Phone;Clinic;Collaborations;Communication;Community Health Systems;comorbidity;cost;Data;data harmonization;design;Devices;digital divide;digital health;digital healthcare;digital treatment;Disparity;Disparity population;disparity reduction;Dissemination and Implementation;effectiveness/implementation hybrid;Engineering;Ensure;Equity;Ethics;Ethnic Origin;Evidence based practice;Evidence based treatment;Failure;Feedback;Glass;health disparity populations;health equity;Health Services Accessibility;Health system;Healthcare;Healthcare Systems;high risk;Hispanic;Home;Human Resources;implementation context;implementation cost;implementation evaluation;implementation outcomes;implementation science;implementation strategy;implementation study;improved;Individual;Inequity;innovation;Intervention;Laboratories;Language;Latino;Leadership;Learning;Medicine;member;Mental Health Services;Mentors;Methodology;Modeling;Outcome;Ownership;Patient Care;patient subsets;Patient-Focused Outcomes;Patients;Perception;Performance;Persons;Phase;Population Heterogeneity;pragmatic trial;Primary Care;primary care clinic;primary care clinician;primary care patient;primary care team;primary care visit;Privacy;Privatization;Problem Solving;Public Health;Race;Randomized;Research;Research Design;Research Personnel;Research Project Grants;Role;Service provision;social determinants;social stigma;Spanish;standardize measure;Statistical Methods;stem;substance use;Substance Use Disorder;substance use treatment;success;System;Testing;Time;United States National Academy of Sciences;United States National Institutes of Health;Visit;Washington;web-based intervention;World Health

PROJECT_TITLE: C-DIAS RP3: Scaling-out app-based treatments: a multi-level strategy to promote equity across primary care patients with substance use


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Nutrition;Physical Activity

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Many people suffer from Heart Failure with Preserved Ejection Fraction (HFpEF), but unfortunately, we do not have any drug treatments that consistently improve a patient’s ability to exercise or his/her quality of life in this syndrome. The goal of this proposal is to test whether improving skeletal muscle metabolism and energy production can improve exercise tolerance in HFpEF patients. We hope that this proposal will identify new ways to treat HFpEF patients, allowing these individuals, who are currently very limited in what they can do and how they feel, to enjoy life more.

PI_NAMEs: ZAMANI, PAYMAN  (contact)

PROGRAM_OFFICER_NAME: TINSLEY, EMILY

PROJECT_TERMS: Acetyl Coenzyme A;active control;Activities of Daily Living;acylcarnitine;Adipose tissue;Animal Model;Aorta;Attention;Basal metabolic rate;Bioenergetics;Biogenesis;Biological Availability;Biopsy;Blood;Blood flow;Blood Vessels;Carbohydrates;Carbon Dioxide;Cardiac Output;Cardiovascular Diseases;Cell Respiration;Clinical Trials;Consumption;Cross-Over Trials;Data;Disease;Double-Blind Method;EFRAC;electric impedance;endurance exercise;Epidemic;Ergometry;Essential Fatty Acids;Exercise;exercise capacity;Exercise Test;Exercise Tolerance;Exertion;exhaustion;fatty acid oxidation;Fatty Acids;Functional impairment;Glucose;Goals;Heart failure;Hemoglobin;Imaging Techniques;Impairment;improved;In Vitro;in vivo;in vivo imaging;Individual;inhibitor;insight;Intervention;Intramuscular;Ketone Bodies;Ketones;Kinetics;Life;Link;Magnetic Resonance Imaging;Measurement;Measures;Mediating;Mediator;Metabolic;Metabolism;metabolome;Mitochondria;Muscle;Muscle Fibers;Muscle Mitochondria;Myocardium;Nitric Oxide;Nitric Oxide Donors;Nonesterified Fatty Acids;novel;oxidation;Oxidative Phosphorylation;Oxygen;Oxygen Consumption;Palmitates;Participant;Pathway interactions;Patients;Perfusion;Permeability;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phenotype;Plasma;Play;Population;Potassium Chloride;potassium nitrate;preservation;prevent;primary endpoint;Production;protein expression;Proteome;Quality of life;Randomized;Respiration;respiratory;restoration;Signal Transduction;Site;Skeletal Muscle;skeletal muscle metabolism;Sodium;Source;symporter;Syndrome;targeted treatment;Techniques;Testing;therapeutic target;Time;Triglycerides;uptake;Venous;Walking;Work

PROJECT_TITLE: Multidrug Metabolic Approach to Improve Exercise and Skeletal Muscle Oxidative Capacity in HFpEF

STUDY_SECTION: CICS

STUDY_SECTION_NAME: Clinical and Integrative Cardiovascular Sciences Study Section[CICS]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Infectious Diseases;Microbiome;Orphan Drug;Prevention;Rare Diseases;Tobacco;Tobacco Smoke and Health

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE The food additive nisin has been increasingly recognized for its broad-spectrum bactericidal action and immunomodulatory effects in both animals and humans; however, its clinical benefit in improving outcomes of human oral cancer patients has not been explored. Here, we will conduct a Phase I/IIa trial of nisin in patients with oral squamous cell carcinoma to establish tolerability and feasibility of the treatment regimen. In parallel, we will analyze patient biological samples for nisin-induced changes in oral microbiome diversity, inflammasome expression, and anti-cancer cellular responses, which we predict are the mechanisms through which nisin promotes an anti-tumorigenic environment and protects against oral cancer.

PI_NAMEs: KAPILA, YVONNE L (contact);YOM, SUE S.

PROGRAM_OFFICER_NAME: XI, DAN

PROJECT_TERMS: Adjuvant;Adverse event;Alcohol consumption;Anatomy;Animals;anti-cancer;Anti-Inflammatory Agents;antimicrobial;antitumor effect;Apoptosis;Bacteria;bactericide;bacteriocin;Biological;cancer cell;Cancer Patient;cancer recurrence;cancer risk;cancer therapy;cancer type;carcinogenesis;carcinogenicity;cell motility;Cell Proliferation;Cells;chemokine;Chronic;Clinical;Clinical Trials;cohort;Communities;Complex;cytokine;demographics;dental biofilm;Dental Hygiene;Detection;Development;Diet;Dietary intake;differential expression;Disease;Dose;dysbiosis;effective therapy;Elements;Enrollment;Environment;Environmental Risk Factor;Enzyme-Linked Immunosorbent Assay;Evolution;Excision;Food Additives;Food Preservatives;Frequencies;fungus;Future;Genetic Transcription;Goals;Gram-Positive Bacteria;Growth;Head and Neck Cancer;head and neck cancer prevention;Heavy Drinking;high risk population;Homeostasis;Human;Human Microbiome;Human papilloma virus infection;Human Papilloma Virus Vaccination;Immunohistochemistry;immunoregulation;Immunotherapy;improved;improved outcome;In Vitro;in vivo;Incidence;Individual;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;insight;Investigation;Link;malignant mouth neoplasm;Malignant Neoplasms;malignant oropharynx neoplasm;Maximum Tolerated Dose;Measures;Mediating;metagenomic sequencing;Metastatic/Recurrent;microbial;Microbial Biofilms;microbial composition;migration;modifiable risk;mouse model;Mouth Diseases;mouth squamous cell carcinoma;multiple omics;Nisin;novel;novel therapeutics;Operative Surgical Procedures;Oral;oral bacteria;Oral cavity;Oral Characters;oral microbiome;oral plaque;Oral Stage;oral tumorigenesis;Organism;Outcome;Participant;pathogen;pathogenic bacteria;Patient-Focused Outcomes;Patients;Periodontal Diseases;Perioperative Adjuvant Therapy;Phase;phase I/IIa trial;Population;Prevalence;primary endpoint;Progression-Free Survivals;Proliferating;Protozoa;Quantitative Reverse Transcriptase PCR;Radiation therapy;Recurrence;Regimen;Research;resident commensals;Resistance;response;Risk;Risk Factors;Role;rRNA Genes;Safety;Saliva;saliva sample;Sampling;Shotguns;Signaling Molecule;smoking cessation;Specimen;Structure;Survival Rate;targeted treatment;Therapeutic;time use;Tissue-Specific Gene Expression;Tissues;Tobacco use;Toll-like receptors;transcriptome sequencing;treatment duration;Treatment Protocols;treatment response;tumor;tumor progression;tumorigenesis;tumorigenic;Virus

PROJECT_TITLE: Oral microbiome and inflammatory status in antimicrobially-treated oral cancer patients


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

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

ORG_CITY: ANN ARBOR

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE To ensure equitable access to scientific advances, datasets must include patients reflecting the demographic distribution of disease. But our previous research demonstrates that many patients are uncomfortable with hospitals sharing their data with industry, and that individuals who identify as Black or Hispanic are consistently more likely to report discomfort. This research aims to explore and characterize hospital data-sharing practices with industry as well as patient response in order to identify areas for compromise that are respectful of individual patient autonomy and equitable in impact across diverse communities.

PI_NAMEs: SPECTOR-BAGDADY, KAYTE KELLEHER (contact)

PROGRAM_OFFICER_NAME: COLLIER, ELAINE S

PROJECT_TERMS: Address;Area;Artificial Intelligence;Asian;Biotechnology;Black race;Characteristics;cohort;Communities;Data;Data Set;data sharing;data sharing networks;design;Disease;Ensure;Equity;ethical, legal, and social implication;Ethnic Origin;evidence base;Exclusion;General Practices;Goals;health disparity;Hispanic;Hospitals;improved;Individual;individual patient;Industry;Inequity;innovation;interest;Interview;Knowledge;Life;Measures;Methodology;Methods;Not Hispanic or Latino;Other Genetics;patient response;Patients;Policies;Positioning Attribute;precision medicine;preference;Prevalence;Race;Remunerations;Reporting;Research;Research Personnel;response;Sampling;Scientific Advances and Accomplishments;skills;Structure;Surveys;Technology;translational impact;Translational Research;Translations;Writing

PROJECT_TITLE: Hospitals Sharing Patient Data and Biospecimens with Commercial Entities: Evidence-Based Translation to Improved Practice


NIH_SPENDING_CATS: Cancer;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Uterine Cancer;Women's Health Research

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE The incidence of early-onset endometrial cancer has risen in young obese patients. The proposed study will result in the development of screening methods using methylation markers in cell-free DNA testing. Furthermore, given PAI-1 plays a role in comorbidity complications, the study may open new preventive measures targeting downstream PAI-1 pathways.

PI_NAMEs: HUANG, TIM H.-M.;KIRMA, NAMEER  (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Address;Adhesiveness;adipokines;Adipose tissue;Age;Atomic Force Microscopy;Attenuated;Biological Assay;Biophysics;Blood;cancer cell;cancer recurrence;cancer subtypes;Caring;cell free DNA;cell motility;Cell Polarity;Cell secretion;Cell Shape;Cell surface;cell type;Cells;chromatin immunoprecipitation;Clinic;Clinical;Coculture Techniques;cohort;comorbidity;demographics;Development;Disadvantaged;Disease;Disparity;DNA Methylation;DNA Modification Methylases;DNMT3B gene;Dyes;early onset;Elasticity;Endometrial;Endometrial Carcinoma;Epidemic;epigenetic marker;Epigenetic Process;epigenetic silencing;Epithelial Cells;experience;Exposure to;Expression Profiling;Extracellular Matrix;Fertility;fertility preservation;food desert;Future;Gene Expression;Genes;Genetic Transcription;Growth;Health Insurance;high body mass index;Homeostasis;Hormones;Hypermethylation;Immune;in vivo;Incidence;Infiltration;insight;Insulin Resistance;intercellular communication;Ions;knock-down;LDL-Receptor Related Protein 1;Link;MADH4 gene;Malignant Neoplasms;Mediating;Medical;Metabolic syndrome;metaplastic cell transformation;Methodology;Methods;Methylation;methylation biomarker;Methyltransferase;Modeling;Molecular;Monitor;neoplastic;Neoplastic Epithelial Cell;novel;obese patients;Obesity;Onset of illness;paracrine;Pathway interactions;Patients;Permeability;Phenotype;Plasminogen Activator Inhibitor 1;Play;Predisposition;Preventive measure;Primary Neoplasm;Prognosis;programs;Proliferating;promoter;Property;Protein C Inhibitor;protein protein interaction;Proteomics;recruit;Recurrence;Recurrent disease;Repression;Risk;Role;rural area;Sample Size;Sampling;screening;Signal Transduction;Signaling Molecule;single-cell RNA sequencing;Socioeconomic Factors;Stromal Cells;Testing;Time;Tissue Microarray;transcriptional reprogramming;Transforming Growth Factor beta;Travel;tumor;tumor microenvironment;tumorigenesis;Ubiquitin;Up-Regulation

PROJECT_TITLE: PAI-1-mediated early-onset endometrial cancer


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Brain Disorders;Clinical Research;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: DURHAM

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DUKE UNIVERSITY

PHR: Relevance Statement Recent years have witnessed an explosion of information derived from genome wide association studies (GWAS) linking genetic variation with increased risk for diseases such as Multiple Sclerosis (MS). To date, little mechanistic insight has been gleaned from the majority of risk-associated variants, a challenge reflecting their primary localization to non-coding regulatory regions of the genome. The proposed work will capitalize on emerging genomics approaches to prioritize lineage-relevant MS risk variants, determine their mechanism of action in contributing to the pathogenesis of MS, and as such, provide new avenues for therapeutic interventions targeting MS.

PI_NAMEs: CIOFANI, MARIA  (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: analytical method;Antigens;Autoimmunity;Automobile Driving;Binding;Bioinformatics;Biological Assay;Brain;causal variant;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Central Nervous System;Cerebrospinal Fluid;Chromatin;Chromatin Loop;Chronic;Clinic;Clinical;Core Facility;CRISPR/Cas technology;Data;Demyelinations;Development;Disease;Disease susceptibility;disorder risk;Elements;Enhancers;Environmental Risk Factor;Epigenetic Process;epigenome editing;Etiology;Experimental Autoimmune Encephalomyelitis;experimental study;Explosion;Functional disorder;Gene Expression Profile;Gene Expression Regulation;Gene Targeting;gene therapy;Genes;Genetic;genetic variant;Genetic Variation;Genome;genome wide association study;Genomic approach;Genomics;Genotype;Glean;Goals;Human;Immune system;Immunologist;In Vitro;in vivo;Infiltration;Inflammatory;insight;Knowledge;Link;Machine Learning;machine learning prediction;Maps;Mediating;Methods;Modeling;Molecular;Molecular Conformation;mouse model;multiple omics;Multiple Sclerosis;multiple sclerosis patient;Mus;Myelin;neuroimmunology;neuroinflammation;Neurology;novel;Nucleic Acid Regulatory Sequences;Pathogenesis;Pathogenicity;Patients;Phenotype;Physiological;Physiology;promoter;Regulator Genes;Regulatory Element;Reporter;Research Personnel;Risk;risk variant;Role;Sampling;Scientist;single cell ATAC-seq;single cell genomics;Specialist;Spinal Cord;stem;T cell response;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Th1 Cells;Therapeutic Intervention;transcription factor;Transcriptional Regulation;Untranslated RNA;Variant;Work

PROJECT_TITLE: Deciphering the role of noncoding variation in the pathogenesis of multiple sclerosis

STUDY_SECTION: HAI

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Breast Cancer;Cancer;Diethylstilbestrol (DES);Endocrine Disruptors;Estrogen;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Women's Health Research

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Exposures to chemicals that mimic the estrogen hormone increase the risk of a woman developing breast cancer later in life. We have identified changes to the mammary gland following estrogen-like chemical exposures that are associated with breast cancer risk. The goal of this proposal is to determine how the hormone-like activity of these chemicals causes mammary gland changes and the role they play in increasing risk of developing cancer.

PI_NAMEs: BURD, CRAIG J (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Acute;Adult;Age;Animal Model;Architecture;Automobile Driving;Biochemical;Biochemistry;Biological;Biological Markers;Biological Models;Biology;biomarker identification;Biophysics;bisphenol A;Breast;Breast Cancer Risk Factor;breast density;breast tumorigenesis;cancer initiation;cancer risk;Chemical Exposure;Chemicals;Clinical;Clinical Research;Collagen;Consensus;Data;Daughter;Deposition;Development;dichlorodiphenyltrichloroethane;Diethylstilbestrol;Disease susceptibility;Elasticity;Endocrine disruption;Endocrine Disruptors;Environment;Environmental Exposure;Epigenetic Process;Epithelium;ESR1 gene;estrogenic;estrogenic activity;Estrogens;Event;Exhibits;Exposure to;Extracellular Matrix;Fibroblasts;Foundations;Genetic;Goals;Hormones;in utero;Incidence;Individual;Industrial Product;Life;Link;Maintenance;Malignant Breast Neoplasm;Malignant Neoplasms;mammary epithelium;Mammary gland;mammary gland development;Mammary Gland Parenchyma;Measures;Mediating;Molecular;Molecular Biology;Molecular Target;Mothers;mouse model;mRNA Expression;Outcome;Pathogenicity;Permeability;Pesticides;Phenotype;Play;Population;Porosity;potential biomarker;Predisposition;Pregnant Women;prenatal exposure;programs;Risk;Role;Screening procedure;Signal Transduction;Stromal Change;Structure;Study models;Testing;therapeutic target;Therapeutic Uses;Tissue Recombination;Tissues;tumorigenesis;Uterus;Woman

PROJECT_TITLE: Defining the role of in utero estrogenic endocrine disruption on mammary gland stiffness and breast cancer risk

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Clinical Research;Emerging Infectious Diseases;Infectious Diseases

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Our ability to effectively treat infections is threatened by increasing resistance among many microbes to the antibiotics that we use today. One approach to the development of new antibiotics is to engineer antimicrobial peptides (AMPs), miniproteins naturally produced by the human body to defend against microbes, which may treat infections both by killing microbes and by promoting an appropriate immune response. This proposal uses protein engineering and related technologies to systematically characterize and engineer human AMPs for the development of new types of antibiotics.

PI_NAMEs: ALBIN, JOHN S. (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: alpha-Defensins;anti-microbial drug;anti-microbial peptide;Antibiotic Resistance;Antibiotics;antimicrobial;antimicrobial peptide LL-37;Antimicrobial Resistance;attributable mortality;beta-Defensins;Biology;career;cathelicidin;cathelicidin antimicrobial peptide;Cessation of life;Chemistry;Chemotaxis;Clinical;clinical training;Combined Modality Therapy;Communicable Diseases;Complex;cytotoxicity;Derivation procedure;Development;drug development;Engineering;Environment;experience;Face;Funding;General Hospitals;genetic approach;Genomics;Goals;Gram-Negative Bacteria;Head;Home;Human;Human body;Human Engineering;Humanities;Immune response;Immune system;Immunology;immunoregulation;Infection;insight;K-Series Research Career Programs;Lead;Libraries;Life;Lipopolysaccharides;Malignant Neoplasms;Mammalian Cell;Maps;Mass Spectrum Analysis;Massachusetts;Mediating;Membrane;Mentors;Microbe;Microbiology;mortality;Natural Products;novel;novel antibiotic class;pathogen;Pathogenesis;Peptide Synthesis;Phagocytes;Phenotype;pre-clinical;programs;Property;Protein Engineering;Proteins;Proteome;Proteomics;rational design;recruit;Research;Resistance;Resources;Scientist;small molecule;Source;Structure;Structure-Activity Relationship;Technology;Testing;Therapeutic;Toxic effect;Training;United States;Work

PROJECT_TITLE: Protein engineering for the development of novel antimicrobial agents

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Osteoporosis

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: PROJECT NARRATIVE  The focus of this project is a group of secreted signaling molecules that play critical roles in regulating bone mass. The overall goal of this project will be to use genetic approaches in mice to elucidate the precise roles of these signaling molecules as well as their inhibitory binding proteins, which we believe will be important for developing the most effective strategies to target this regulatory system for clinical applications to treat patients with bone loss.

PI_NAMEs: GERMAIN-LEE, EMILY L;LEE, SE-JIN  (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: activin A;Activin A type II receptor;Activins;Acute;ACVR2 gene;ACVR2B gene;Affect;Binding Proteins;bone;Bone Density;Bone Diseases;bone loss;bone mass;Bone structure;cell growth regulation;Chronic;clinical application;Complex;Development;Differentiation and Growth;extracellular;Family member;Follistatin;GDF11 gene;GDF8 gene;Genetic;genetic approach;Genetic study;Goals;Growth;Health;Homeostasis;Individual;interest;Ligands;LoxP-flanked allele;Molecular;morphogens;Mus;Muscle;muscle form;Names;novel therapeutic intervention;Osteoblasts;Pathway interactions;Patients;pharmacologic;Pharmacology Study;Physiological;Play;preservation;prevent;receptor;Regulatory Pathway;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Skeletal Muscle;skeletal muscle growth;stem;Subgroup;System;TGF-beta type I receptor;Tissues;tool;Transforming Growth Factor beta;virtual;Work

PROJECT_TITLE: Extracellular regulation of bone mass by transforming growth factor-ß-related ligands and their binding proteins

STUDY_SECTION: SBDD

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: RALEIGH

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: PROJECT NARRATIVE Transcription factors (TFs) regulate gene expression responses to a variety of input signals; and ensuring accurate transmission of this information remains an important challenge in understanding disease progression as dysregulation can lead to autoimmune disorders or cancer. TF p65/RELA regulates hundreds of genes in the NF-κB pathway, including those implicated in inflammation and tumor suppression. Here, we will develop a precisely regulated, optogenetic, single cell, and genome-wide approach to comprehensively characterize dynamic regulation by NF-kB, providing a new platform to gather fundamental knowledge of gene regulation in human cells for downstream applications in therapeutics and biomedical engineering.

PI_NAMEs: CAYWOOD, LEANDRA  (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Address;Affect;Autoimmune Diseases;biological systems;Biomedical Engineering;Bypass;Cell Line;Cells;cellular engineering;Chemical Stimulation;Cues;Development;differential expression;Disease;Disease Progression;Dissection;Ensure;Environment;environmental stressor;Eukaryotic Cell;experience;Exposure to;extracellular;Fibrinogen;Fluorescence;Fluorescence Microscopy;Foundations;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genes;Genetic Transcription;genome-wide;Hela Cells;Heterogeneity;Human;Immune response;Immune System Diseases;Individual;Inflammation;interest;Knock-out;Knowledge;Lead;Light;Malignant Neoplasms;Maps;Masks;Measurable;Methods;Modeling;Modernization;Nature;NF-kappa B;NF-Kappa B p65;Nuclear;Nuclear Translocation;optogenetics;p65;Pathway interactions;Pattern;Perception;phenomenological models;Phenotype;Polymerase Chain Reaction;Population Heterogeneity;programs;Proliferating;promoter;Regulation;RELA gene;Research;response;Reverse Transcription;Signal Transduction;single-cell RNA sequencing;Stimulus;Stretching;synthetic biology;System;Techniques;Technology;Therapeutic;TNF gene;tool;transcription factor;Transcriptional Regulation;transcriptome;transcriptomics;transmission process;Tumor Suppression;Validation;whole genome;Work

PROJECT_TITLE: Single cell, genome wide dissection of dynamic transcription factor regulation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-M(20)L]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Biomedical Imaging;Clinical Research;Contraception/Reproduction;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Women's Health Research

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Preterm birth is the greatest and costliest burden in perinatology and it not only results in a high rate of fetal mortality but also puts the children at a lifelong risk of negative health consequences. However, the factors that result in preterm birth are still not very well understood, which is largely due to our limited ability to monitor the human uterine maturation with sufficient spatial and temporal resolutions. We propose to investigate the feasibility of a wirelessly powered, wearable patch system capable of providing high-resolution three-dimensional mapping of uterine surface electrical activity during contractions, which would permit the study of birth-related risks and improve maternal and child outcomes.

PI_NAMEs: WANG, CHUAN  (contact)

PROGRAM_OFFICER_NAME: LONGO, MONICA

PROJECT_TERMS: 3-Dimensional;Abdomen;Address;Adoption;Area;Benchmarking;Birth;Body of uterus;Body Surface;Brain;Cerebral Palsy;Child;Clinical;clinical application;clinical translation;Clinical Treatment;cohort;cost;Data;Delivery Rooms;density;design;effectiveness evaluation;Electric Capacitance;electrical property;Electrodes;Engineering;Fetal Monitoring;Fetal Mortality Statistics;Geometry;Health;hearing impairment;Heart;Heart failure;Home;Human;human subject;Image;imaging platform;imaging study;imaging system;Imaging technology;Impaired cognition;improved;instrument;instrumentation;Joints;Knowledge;Magnetic Resonance Imaging;Maps;Measurement;Measures;mechanical properties;Medical center;member;Mental Retardation;Methods;Monitor;Morphologic artifacts;Motion;new technology;novel;Organ;Outcome;Outpatients;Pathologic;patient mobility;Patients;Pattern;Performance;Perinatology;Persons;portability;Pregnancy;Pregnant Women;Premature Birth;Premature Labor;prevent;Printing;Research;Research Activity;Resolution;Risk;Schedule;sensor;Signal Transduction;Site;Surface;System;Technology;Telemetry;temporal measurement;tool;Transducers;Translating;treatment strategy;United States;Universities;Uterine Contraction;Uterine Monitoring;Uterus;Validation;Visual impairment;Washington;wearable device;wireless;Wireless Charging

PROJECT_TITLE: A self-capacitance driven wearable electromyometrial imaging system for maternal and fetal monitoring during pregnancy and labor

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Kidney Disease;Prevention

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Project Narrative: Renal ischemia/reperfusion injury (IRI) occurs commonly in hospitalized patients and mechanistic evaluations are urgently needed in order to develop preventive and therapeutic strategies. The PI’s laboratory has found that blockade of an intracellular pattern recognition receptor (NLRP3) prevents injury to the kidney following experimental reduction of blood flow. The proposed project examines the mechanisms by which NLRP3 signaling is regulated, and can be effectively targeted, in renal tubular epithelial cells.

PI_NAMEs: MCKAY, DIANNE B (contact)

PROGRAM_OFFICER_NAME: SADUSKY, ANNA BURKART

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Address;antimicrobial;Blood flow;Blood Vessels;Bone Marrow Transplantation;Cell Death;Cell Death Signaling Process;cell type;Cells;Cellular Stress;Clinical;clinical development;clinically relevant;Complex;cytokine;Cytoplasm;Data;defense response;design;detector;Development;Disease;Elements;Engineering;Epithelial Cells;Epithelium;Evaluation;experimental study;Functional disorder;gain of function mutation;genetic approach;Goals;Health;Hospitalization;Host Defense;Human;Hypoxia;IL18 gene;Immune;Immunologic Receptors;Impairment;improved;in vivo;in vivo Model;infection risk;Inflammasome;Inflammatory Infiltrate;injured;Injury;Injury to Kidney;Innate Immune System;Ischemia;Kidney;Knowledge;Laboratories;Learning;loss of function;Mediating;medication safety;meetings;Modeling;Mus;novel therapeutic intervention;Operative Surgical Procedures;organ injury;Organ Procurements;Outcome;Pathway interactions;Patients;Pattern recognition receptor;Play;pre-clinical;preservation;prevent;Prevention therapy;Preventive;Production;Proteins;Proximal Kidney Tubules;renal hypoxia;renal ischemia;Renal tubule structure;Reperfusion Injury;Reperfusion Therapy;Research;Research Design;Research Methodology;response;response to injury;Role;Sepsis;Shock;Signal Pathway;Signal Transduction;small molecule inhibitor;targeted treatment;Testing;Therapeutic;therapeutic target;tissue injury;Tissues;Transplantation;Tubular formation

PROJECT_TITLE: Role of NLRP3 signals in ischemia/reperfusion-induced organ injury

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

PHR: Program Narrative Double hit lymphoma (DHL) and double-expressing lymphoma (DEL) are highly aggressive incurable B-cell malignancies that are characterized by co-overexpression of two oncoproteins called MYC and BCL2, which drive uncontrolled cell growth and resistance to cell death (for example that caused by chemotherapeutic drugs), respectively. Accordingly, there is a dire need for new therapeutic strategies to treat DHL and DEL and, using a novel cell-based platform and unbiased screening approaches, we discovered that these lymphomas have a unique transcriptional landscape that relies on protein kinases called CDK7 and CDK9 that are necessary to sustain the expression of genes in these lymphomas that control B-cell fate or that function as oncoproteins, including MYC. The proposed studies will define the role and mechanism by which CDK7 and CDK9 sustain DHL growth, survival and tumorigenicity, and will pre-clinically validate a therapeutic strategy that combines drugs that disable CDK7, CDK9 and BCL2 as a new therapeutic approach to treat DHL and DEL patients.

PI_NAMEs: CLEVELAND, JOHN L. (contact)

PROGRAM_OFFICER_NAME: SALOMON, RACHELLE

PROJECT_TERMS: Apoptosis;Apoptotic;B lymphoid malignancy;B-Cell Lymphomas;B-Lymphocytes;BCL1 Oncogene;BCL2 gene;Biology;Bone Marrow;bropirimine;C-terminal;Cancer Cell Growth;Cell Cycle Progression;Cell Death;cell growth;Cell Line;Cell Proliferation;Cell Survival;Cells;Cellular Metabolic Process;Chemicals;chemotherapy;ChIP-seq;Chromosomal Duplication;Chromosomal translocation;Clinical;Clinical Trials;cofactor;Coin;Combined Modality Therapy;Cyclin-Dependent Kinase Inhibitor;Cyclin-Dependent Kinases;Data;data integration;Disease;Drug Combinations;Drug resistance;Drug Screening;Drug Targeting;effective therapy;Enhancers;Foundations;Gene Expression;Genes;Genetic Transcription;genomic profiling;Growth;Histologic;in vivo;inhibitor;kinase inhibitor;Laboratories;large cell Diffuse non-Hodgkin's lymphoma;Leucine Zippers;Lymphoma;Lymphoma cell;Maintenance;Malignant Neoplasms;Metabolism;Modeling;Molecular;Mus;novel;novel therapeutic intervention;novel therapeutics;Oncogenes;Oncogenic;Oncoproteins;Outcome;overexpression;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;Pharmacogenomics;pharmacologic;Pharmacotherapy;Phenotype;Phosphorylation;Phosphotransferases;pre-clinical;programs;Protein Kinase;Proteomics;Publishing;Refractory;Research;Resistance;Resistance development;response;RNA Polymerase II;Role;Sampling;screening;Signal Transduction;Specimen;targeted treatment;Testing;Therapeutic;therapeutic evaluation;therapy resistant;tool;Transcription Elongation;transcription factor;transcriptome;transcriptome sequencing;transcriptomic profiling;Treatment Efficacy;treatment response;tumor microenvironment;Tumorigenicity;uncontrolled cell growth;Up-Regulation

PROJECT_TITLE: New Therapeutic Vulnerabilities for Aggressive B-Cell Lymphoma

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


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

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Funding of this proposal will allow me to train in neuroinflammation, an important process in Alzheimer’s disease (AD) and Alzheimer’s disease related dementias (ADRD). In addition, the proposed scientific project will add the measurement of neuroinflammation to the detailed measurement of amyloid, tau, and neurodegeneration in a unique cohort of middle-aged Hispanics in New York City. This project will support mentoring of a future generation of AD/ADRD investigators.

PI_NAMEs: LUCHSINGER, JOSE ALEJANDRO (contact)

PROGRAM_OFFICER_NAME: ANDERSON, DALLAS

PROJECT_TERMS: Address;aged;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid;Applications Grants;Atrophic;Award;Biological Markers;Brain;Brain imaging;brain magnetic resonance imaging;Brain region;Calendar;cardiometabolic risk;career;Cerebrovascular Disorders;Clinical Investigator;Cognition;Cognitive deficits;cognitive testing;cohort;Collaborations;Data;dementia risk;Diabetes Mellitus;diabetic;Funding;Future Generations;Glial Fibrillary Acidic Protein;Gliosis;glucose tolerance;Goals;Grant;Hispanic;Hispanic Populations;Human;Hyperglycemia;Image;Impaired cognition;Inflammation;Knowledge;Ligands;Light;Link;Magnetic Resonance Imaging;Measurement;Mediating;Memory;Memory impairment;Mentors;metabolomics;Methods;Microglia;Mid-Career Clinical Scientist Award (K24);Midcareer Investigator Award in Patient-Oriented Research;middle age;Mus;Nerve Degeneration;Neurodegenerative Disorders;neurofilament;neuroinflammation;New York City;parent project;Parents;Participant;patient oriented research;Performance;Peripheral;Persons;Pilot Projects;Plasma;Positron-Emission Tomography;Prevention;Process;Proteins;Research;Research Personnel;Resources;Role;Standardization;tau Proteins;Testing;Thick;Time;Training;Training Activity;uptake

PROJECT_TITLE: Midcareer Award for Research in Dementia Risk Factors and Prevention

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Established Investigators and Conference Grants Study Section[AGCD-4]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Aging

ORG_CITY: BOSTON

ORG_NAME: HEBREW REHABILITATION CENTER FOR AGED

PHR: Project Narrative: This training program addresses the critical need for new investigators in the field of aging who can help solve the numerous health-related problems that will soon confront our rapidly aging population. The program will prepare a new cadre of academic leaders in geriatric medicine and aging research, who will be equipped with the necessary skills to understand the aging process, study why it often leads to disease, and determine how to prevent the onset of disease and disability in late life. .

PI_NAMEs: LIPSITZ, LEWIS  (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TITLE: Harvard Translational Research in Aging Training Program


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;Health Services;Hepatitis;Liver Disease;Organ Transplantation;Prevention;Substance Misuse;Transplantation

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Alcohol-associated liver disease represents a growing public health burden, particularly among younger age groups, women, and ethnic minorities, and is now the leading cause of liver transplantation in the United States. This project will identify predictors of outcome and improve prognostication in severely ill patients with alcohol- associated liver disease. Identifying reliable non-invasive markers that characterize the distinct phenotypes of alcohol-associated liver disease will be crucial to advance our understanding of this liver disease, target interventions, and appropriately allocate resources including liver transplantation.

PI_NAMEs: KWONG, ALLISON  (contact)

PROGRAM_OFFICER_NAME: GAO, PETER

PROJECT_TERMS: Abstinence;Academic Medical Centers;Acute;advanced disease;age group;alcohol abstinence;Alcohol consumption;Alcohol Phenotype;alcohol research;alcohol use disorder;Alcoholic Hepatitis;Alcoholic Liver Diseases;Ambulatory Care Facilities;Apoptotic;Ascites;Award;Bacterial DNA;Bilirubin;biobank;Biological;Biological Markers;career;career development;Cessation of life;Characteristics;chemokine;Classification;Clinical;clinical epidemiology;Clinical Investigator;Clinical Research;clinically relevant;cohort;Communication;Communities;Complex;cost;Creatinine;Cytokeratin-18 Staining Method;cytokine;Data;Data Analyses;Dedications;demographics;Development Plans;disease heterogeneity;disease phenotype;Disease Progression;disease registry;ethnic minority;Etiology;experience;Feces;fibrogenesis;Fibrosis;follow-up;Foundations;frailty;Future;Genetic Risk;genetic variant;Hemorrhage;Hepatic;Hepatitis;hepatocyte injury;high risk;Hospitalization;Hospitals;Image;Immunoassay;improved;Inflammation;Inflammatory;Institution;Intervention;Laboratories;lipidome;Lipopolysaccharides;Liver;Liver diseases;liver transplantation;Machine Learning;Measures;Mentorship;microbiome;MicroRNAs;Morbidity - disease rate;mortality;mortality risk;Multicenter Studies;multidisciplinary;Natural History;nutrition;Outcome;outcome prediction;Outcomes Research;Pathway interactions;Patient Care;Patient-Focused Outcomes;Patients;Pattern;pharmacologic;Phenotype;preclinical study;Principal Investigator;Procedures;Process;prognostication;programs;prospective;Psychosocial Influences;Public Health;radiological imaging;Recovery;recruit;Registries;Relaxation;Research;research and development;Research Personnel;Resource Allocation;Resources;Risk;risk prediction model;risk variant;sarcopenia;Serum;Severity of illness;Signal Transduction;skills;sobriety;sociodemographic factors;Subgroup;Susceptibility Gene;Techniques;Technology;Testing;Time;Training;transcriptome;Translating;translational study;Transplant Recipients;Transplantation;United States;Universities;urinary;Visit;Woman

PROJECT_TITLE: Defining Phenotypes of Alcohol-Associated Liver Disease with Acute Hepatic Decompensation

STUDY_SECTION: AA

STUDY_SECTION_NAME: Biomedical Research Study Section[AA-1]


ORG_DEPT: BIOCHEMISTRY

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: PROJECT NARRATIVE Human cytomegalovirus (HCMV) infects the majority of the world’s population for life and can cause severe disseminated infections in immunocompromised patients, e.g., transplant recipients, and a spectrum of developmental abnormalities in neonates. The goal of this proposal is to stabilize glycoprotein gB – a molecular machine that enables HCMV entry and spread – in its biologically-active, prefusion form, characterize its structure and antigenicity, and isolate prefusion-specific neutralizing antibodies from HCMV- seropositive donors. The new reagents and knowledge resulting from the proposed work could lead to a better understanding of HCMV immune response and correlates of protection and aid in the development of optimal vaccines and passive immunization strategies against HCMV.

PI_NAMEs: HELDWEIN, EKATERINA  (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Antibodies;Antibody Response;Antigens;B-Lymphocytes;Binding;Biochemical;Cell membrane;Cells;Closure by clamp;CMV glycoprotein B;Complex;Cryoelectron Microscopy;Cytomegalovirus;Cytomegalovirus Infections;Cytomegalovirus Vaccines;Cytoplasmic Tail;Data;design;Development;Disease;Engineering;Epitopes;Fetus;Frequencies;Glycoproteins;Goals;Herpesviridae;Homologous Gene;Host Defense;Human;Human Activities;Human Herpesvirus 4;human pathogen;Immune response;Immunocompromised Host;immunogenic;Infection;innovation;Knowledge;knowledge of results;Life;Mediating;Membrane;Membrane Fusion;Memory B-Lymphocyte;Molecular Conformation;Molecular Machines;Mothers;Nature;neonate;neutralizing antibody;novel;Passive Immunization;Penetration;Population;Preparation;Prevent viral transmission;Property;prophylactic;Proteins;Reagent;receptor;Regulatory Element;Research;research and development;Resolution;response;restraint;Role;seropositive;Side;Simplexvirus;Site;Sorting;stem;Structure;Testing;Time;tool;Translational Research;Transplant Recipients;vaccination strategy;vaccine candidate;vaccine development;Vaccines;Viral;Work

PROJECT_TITLE: Structure, antigenicity, and function of HCMV fusogen gB


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biodefense and Related Countermeasures;Brain Disorders;Cannabidiol Research;Cannabinoid Research;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Drug Abuse (NIDA only);Emerging Infectious Diseases;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Neurodegenerative;Neurosciences;Substance Misuse

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: HIV infection continues to be a cause of neuropsychological impairment for which there are currently no treatments. Support from a K24 Midcareer Investigator Award in Patient-Oriented Research will allow me to develop mew research directions while mentoring clinically-oriented scientists from diverse backgrounds to prepare them for translational research at the intersection of neuroHIV and substance use.

PI_NAMEs: CHERNER, MARIANA  (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Accounting;addiction;Affect;Anti-Inflammatory Agents;Antioxidants;Award;Biological Markers;biopsychosocial;Brain;California;Cannabidiol;Cannabinoids;career;Career Mobility;Central Nervous System;Chronic;Clinical;Clinical Trials;Clinical Trials Design;cocaine exposure;Communicable Diseases;Communities;Complex;computational neuroscience;Computerized Medical Record;COVID-19;COVID-19 impact;Creativeness;Data;Development;disadvantaged background;Doctor of Philosophy;Dopamine;early-career faculty;Elderly;Environment;Evaluation;experience;faculty mentor;Fellowship;Fostering;Functional disorder;Funding;Funding Opportunities;Future;Goals;health disparity;Hispanic;Hispanic Populations;HIV;HIV Infections;Hospitalization;immune activation;immunoregulation;Impairment;improved;Impulsive Behavior;Individual Differences;Inflammation;Inflammatory;insight;interdisciplinary collaboration;Interdisciplinary Study;interest;Knowledge;Latino Population;Leadership;Learning;Medical;Medicine;Mentors;Methods;Mid-Career Clinical Scientist Award (K24);mid-career faculty;Midcareer Investigator Award in Patient-Oriented Research;Mitochondria;Nature;neuroAIDS;neurobehavioral;Neurocognition;Neurocognitive;neuropsychiatry;Neuropsychology;Oils;Oral;Outcome;Oxidative Stress;Pathology;patient oriented;patient oriented research;Patients;Persons;Plasma;Population;Post-Acute Sequelae of SARS-CoV-2 Infection;Postdoctoral Fellow;Problem Solving;Process;professor;programs;Property;Psychiatry;Psychology;Publications;Regulation;Research;Research Ethics;Research Infrastructure;Research Methodology;Research Personnel;Research Support;Risk Behaviors;Role;SARS-CoV-2 infection;Scientist;skills;Sorbus;Source;Specimen;stimulant use;Substance abuse problem;substance use;Training;Training and Education;Training Programs;translational approach;Translational Research;Universities;Virus Replication;Work

PROJECT_TITLE: Mentoring Clinical Researchers at the Intersection of NeuroHIV and Substance Abuse

STUDY_SECTION: HCCS

STUDY_SECTION_NAME: HIV Comorbidities and Clinical Studies Study Section[HCCS]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Digestive Diseases;Liver Disease;Neurosciences

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Project Narrative The rapidly increasing prevalence and serious complications of type 2 diabetes (T2D) underscore its importance as a public health issue. Despite advances in therapeutic options, optimizing glycemic control still remains an elusive goal. Since excessive glucose production is the main source of increased glucose levels in T2D, understanding mechanisms that regulate glucose production would have important therapeutic implications. Our recent data suggest that the brain exerts important restraining effects on the liver’s glucose production, but that elevated fatty acid levels in T2D impair this regulation. Using studies in both humans and rats, we hope to clearly elucidate the impact of fatty acids on the cells in the brain that control glucose production. These studies could therefore lead to new therapeutic target(s) for the treatment of T2D.

PI_NAMEs: HAWKINS, MEREDITH A (contact);ROUTH, VANESSA H

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Address;antioxidant enzyme;ATP sensitive potassium channel complex;Beta Cell;Blood Glucose;blood glucose regulation;Brain;brain control;Cells;Central Nervous System;Chronic;Closure by clamp;Complications of Diabetes Mellitus;Data;Defect;Diabetes Mellitus;diabetic;diabetic rat;Diazoxide;endoplasmic reticulum stress;euglycemia;extracellular;Fasting;Fatty Acids;Glucose;glucose production;glycemic control;Goals;Hepatic;Human;Hyperglycemia;Hypothalamic structure;Impairment;Individual;Infusion procedures;Insulin;Lead;Lipids;Liver;liver transplantation;Mediating;Mitochondria;nerve supply;Neurons;new therapeutic target;Nicotinic Acids;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Nonesterified Fatty Acids;novel therapeutics;Nutritional status;Obesity;Organ;overexpression;Pancreas;patch clamp;Patients;Play;Population;Potassium;Prevalence;prevent;Process;Public Health;Rattus;Regulation;Regulatory Pathway;restoration;restraint;Rodent;Role;Signal Pathway;Signal Transduction;Somatostatin;Source;Testing;Therapeutic;Transplant Recipients;TXN gene;Work

PROJECT_TITLE: Restoring Central Regulation of Glucose Production in Type 2 Diabetes

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

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

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: The objective of this project is to understand the sources and routes of transmission for Shigella and Campylobacter, two important causes of diarrhea in young children, in an urban low-resource setting in Dhaka, Bangladesh. We will follow a longitudinal transmission cohort of households to identify and attribute sources of infections. These data will inform mathematical models to determine the relative importance of person-to-person and environmental transmission pathways. This project will transform our understanding of enteric pathogen transmission by moving from a broad understanding of fecal-oral transmission routes to pathogen-specific household and environmental pathways of highest relevance.

PI_NAMEs: PLATTS-MILLS, JAMES ALEXANDER;TANIUCHI, MAMI  (contact)

PROGRAM_OFFICER_NAME: JESSUP, CHRISTINE

PROJECT_TERMS: Animals;Bangladesh;burden of illness;Campylobacter;Child;cohort;Culture-independent methods;Data;detection method;Development;Diarrhea;dynamic system;Ecology;enteric pathogen;Environment;Environmental Pollution;exposure route;Exposure to;Feces;Genome;Household;Human;Hybrids;Incidence;indexing;Infection;Longitudinal Studies;mathematical model;Measures;metagenomic sequencing;Methods;model organism;Modeling;Molecular;molecular diagnostics;Nucleic Acids;Oral;Organism;pathogen;Pathogen detection;Pathway interactions;Persons;Resource-limited setting;Route;Sampling;Shigella;Slum;Source;Structure;transmission process;urban setting

PROJECT_TITLE: Source Attribution and Transmission Dynamics of Campylobacter and Shigella Using Culture-Independent Molecular Methods in an Urban Slum in Dhaka, Bangladesh


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_CITY: IOWA CITY

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative: Cochlear implants are one of the most successful biological implants, and while these devices provide hearing to people who have lost significant hearing, most ears implanted with a CI have inflammatory reactions to the device that negatively affects their performance. The implant is made of materials that cause an inflammatory reaction that results in scar formation and limits the ability of the device to provide optimal hearing. In the proposed work, we will perform experiments in mice to investigate the effects of the biomaterials that are used to make cochlear implants and the effects of electrical stimulation to understand how these aspects of cochlear implantation influence inflammation and scar formation in the cochlea.

PI_NAMEs: HANSEN, MARLAN R (contact);HIROSE, KEIKO

PROGRAM_OFFICER_NAME: MILLER, ROGER

PROJECT_TERMS: 3-Dimensional;Ablation;Acoustics;Action Potentials;Adhesions;Affect;Architecture;Auditory Brainstem Responses;battery life;Biocompatible Materials;Biological;capsule;Cells;Charge;chemokine;Cicatrix;Clinical;Cochlea;Cochlear implant procedure;Cochlear Implants;Collagen;confocal imaging;CSF1R gene;Data;density;Devices;Ear;Effectiveness;electric impedance;Electric Stimulation;Electrodes;Electrophysiology (science);Encapsulated;Environment;Equipment Malfunction;Evaluation;experimental study;Fibroblasts;Fibrosis;flexibility;Foreign Bodies;Foreign-Body Reaction;Fractalkine;Frequencies;Future;Genetic;Goals;Health;Hearing;Housing;Implant;implantation;Implanted Electrodes;improved;In Vitro;Inflammation;Inflammatory;inhibitor;Injury;Intervention;Investigation;Knockout Mice;Macrophage;Macrophage Activation;Measures;Mechanics;microscopic imaging;Modeling;mouse model;Mus;Operative Surgical Procedures;Oral Administration;Osteogenesis;otoacoustic emission;Outcome;Patients;Performance;Persons;Physiologic Ossification;Platinum;platinum electrode;Play;polydimethylsiloxane;pre-clinical;preservation;Process;Property;Reaction;recruit;Regulation;Reporter;Residual state;response;Role;Scala Tympani;Signal Transduction;Silicones;Stimulus;Surface;Surface Properties;System;Testing;Therapeutic Studies;Time;Tissues;translational model;Trauma;Work;X ray microscopy

PROJECT_TITLE: Role of Macrophages on Tissue Remodeling Following Cochlear Implantation


ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Narrative The proposed research is relevant to public health because a better understanding of metabolism of T lymphocyte is expected which will help us design therapies and treatments of various immune diseases. Thus, the proposed research is relevant to the part of NIH's mission that pertains to pursuit of fundamental knowledge about the nature of human health systems.

PI_NAMEs: CHANG, CHEONG-HEE  (contact)

PROGRAM_OFFICER_NAME: KELLY, HALONNA R

PROJECT_TERMS: Adipose tissue;Adopted;aerobic glycolysis;Area;arm;Autoimmune Diseases;Biochemical Pathway;Bioenergetics;cancer cell;Carbon;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Cycle Progression;Cell Physiology;Cell Respiration;Cell Survival;Cells;Cellular Metabolic Process;Chronic;cytokine;Cytotoxic T-Lymphocytes;cytotoxicity;Data;Development;Diabetes Mellitus;Ectopic Expression;Environment;Enzymes;Equilibrium;Exhibits;Experimental Models;Gene Expression;Generations;Glucose;glucose metabolism;glucose uptake;Glutamates;Glutamine;Glutathione;Glycolysis Induction;Growth;Health system;Human;Human Characteristics;Immune response;Immune System Diseases;Infection;Inflammatory;innovation;insight;Interferons;Knowledge;Liver;macromolecule;Malignant Neoplasms;Measures;Mediating;Memory;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Mission;Mitochondria;Outcome;Outcome Study;Oxidative Phosphorylation;Pathogenesis;Pentosephosphate Pathway;Phenotype;Play;Population Heterogeneity;Production;programs;Proliferating;Public Health;Publishing;Reactive Oxygen Species;Regulation;Research;response;Rest;Role;Signal Pathway;Signal Transduction;Site;Source;Starvation;T cell differentiation;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Testing;therapy design;Thymus Gland;Time;Tissues;United States National Institutes of Health;virtual;ZNF145 gene

PROJECT_TITLE: Regulation of metabolic pathways in NKT cells

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Data Science;Drug Abuse (NIDA only);Genetics;HIV/AIDS;Human Genome;Infectious Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: PROJECT NARRATIVE  The proposed study is to leverage high-dimensional, multi-scale, and highly heterogeneous genomics data to discover the essential molecular alterations of immune cells introduced by HIV and/or substance use disorder (SUD) at a single-cell resolution. In contrast to existing methods that rely on either transcriptome or epigenome only, this work assumes that several key transcriptomic, epigenetic, and regulatory network alterations jointly occur with HIV and/or SUD, resulting in immune system dysfunction. Hence, we propose a computational framework to depict the comprehensive immune cell regulome, construct molecular networks of various cell types, and pinpoint key immune dysfunction driver events at a single-cell resolution.

PI_NAMEs: GERSTEIN, MARK BENDER (contact)

PROGRAM_OFFICER_NAME: POLLOCK, JONATHAN D

PROJECT_TERMS: Acceleration;adaptive immunity;Affect;ATAC-seq;Atlases;Behavior;Big Data;Binding;Biological Assay;Biological Process;CD4 Positive T Lymphocytes;cell type;Cells;Cellular Immunity;Communities;Companions;Complex;computer framework;Computing Methodologies;Data;data hub;Data Set;Databases;Development;Disease;disorder risk;Distal;Enhancers;Epigenetic Process;epigenome;Event;experience;experimental study;functional genomics;Gene Expression Regulation;gene network;gene regulatory network;General Population;Genes;Genetic;Genetic Transcription;genomic data;genomic profiles;Hi-C;high dimensionality;HIV;HIV Infections;Human Cell Line;Humoral Immunities;Immune;immune function;Immune System Diseases;immune system function;in vivo;Incidence;Individual;Injections;insight;Link;machine learning method;machine learning model;Maps;Methods;Modeling;Molecular;molecular dynamics;Molecular Profiling;multidimensional data;multimodality;Multiomic Data;multiple omics;Natural Immunity;novel;novel sequencing technology;open source;opioid epidemic;opioid overdose;opioid use disorder;Pathogenesis;Persons;pharmacologic;Phenotype;Physiological;Prevalence;programs;promoter;public database;public health emergency;PubMed;Quantitative Trait Loci;Regulatory Element;Reporting;Research;Research Personnel;Resolution;Resources;Risk Factors;Role;Series;single-cell RNA sequencing;substance use;Substance Use Disorder;Technology;text searching;therapeutic target;tool;transcription factor;transcriptome;transcriptomics;transfer learning;transmission process;Twitter;United States;Viral;web services;Work

PROJECT_TITLE: A Big Data Approach to Identify Epigenetic, Transcriptomic, and Network Dynamics as Immune Dysfunction Drivers Associated with HIV Infection and Substance Use Disorder


ADMINISTERING_IC: NS

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: RICHARDSON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: PROJECT NARRATIVE Vagus nerve stimulation (VNS) paired with rehabilitation exercises is currently the only FDA approved neuromodulation therapy for recovery of upper limb function after stroke, and understanding the mechanisms of VNS efficacy is key to improving patient responses to this novel treatment approach. Noradrenaline, an important plasticity-promoting neuromodulator, is thought to mediate many of the effects of VNS, and our labs have recently found that cortical noradrenergic signaling, in particular, is likely to play a critical role in VNS efficacy. The proposed research aims to causally examine the importance of VNS-dependent engagement of the central noradrenergic network in driving motor system synaptic plasticity and functional recovery after stroke.

PI_NAMEs: THORN, CATHERINE A (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Agonist;antagonist;atomoxetine;Attention deficit hyperactivity disorder;Automobile Driving;Behavioral;Cells;Chronic;chronic stroke;clinical translation;Development;disability;effective therapy;Effectiveness;exercise rehabilitation;Exhibits;experimental study;FDA approved;Fiber;Forelimb;Guanfacine;improved;Individual;Infusion procedures;inhibitor;Injury;Intervention;Ischemic Stroke;Lesion;locus ceruleus structure;Mediating;method development;Motor;Motor Cortex;motor function recovery;motor impairment;motor rehabilitation;neocortical;nerve injury;nerve supply;Neurobiology;Neuromodulator;Neuronal Plasticity;Neurons;neuroregulation;noradrenergic;Norepinephrine;novel;novel strategies;optogenetics;Participant;patient response;Patients;Performance;Persons;Pharmaceutical Preparations;pharmacologic;Phase;Physiological;Play;post stroke;pre-clinical;Pre-Clinical Model;Publishing;Quality of life;Rattus;receptor;Receptor Signaling;Recovery;Recovery of Function;Rehabilitation therapy;Research;reuptake;Role;Signal Pathway;Signal Transduction;Stroke;stroke model;stroke patient;stroke recovery;stroke rehabilitation;Synapses;Synaptic plasticity;System;Techniques;Testing;Therapeutic Effect;Tracer;Training;Treatment Efficacy;treatment response;treatment strategy;United States;Upper Extremity;vagus nerve stimulation;Validation;Viral;Work

PROJECT_TITLE: Noradrenergic mechanisms of vagus nerve stimulation mediated stroke rehabilitation

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Mental Health;Neurodegenerative;Neurosciences;Violence Research;Women's Health Research

ORG_CITY: BELMONT

ORG_NAME: MCLEAN HOSPITAL

PHR: Project Narrative Aggression accompanies a number of common human neurodegenerative disorders (e.g. Alzheimer's and other related dementias), with little understanding of how cognitive and aggression symptoms may be linked at the neuronal level. Aggression has been extensively studied in males of many species, but neglected in females (likewise, the interaction of sex and age is neglected). The objective of this research program is to identify the neural circuitry that governs female aggression (K99- mentored phase) and later transition (R00- independent phase) into discovering mechanisms of dementia-related pathology and how these changes affect aggression.

PI_NAMEs: PALAVICINO-MAGGIO, CAROLINE  (contact)

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Abdomen;Address;Affect;Age;age-related disease;Aggressive behavior;Aging;aging related disease;Agitation;Alzheimer's Disease;Amyloid beta-42;Amyloid beta-Protein;Animals;Area;Behavior;behavior change;behavior test;Behavioral;Biological;Body part;Brain region;bullying;Candidate Disease Gene;candidate identification;Cells;cholinergic;cholinergic neuron;Cognitive;Collaborations;common symptom;Complex;Computer software;connectome;Data;Defect;Dementia;design;Development;Dimensions;Disease;disease model;Drosophila genus;Drosophila melanogaster;Electron Microscopy;extracellular;Female;fighting;fly;Ganglia;Gene Cluster;gene conservation;Gene Expression;Genes;Genetic;genetic manipulation;Genetic Transcription;Genome;Human;Instinct;instrumentation;Label;Lateral;Lead;Learning;Libraries;life span;Link;machine learning algorithm;male;Mammals;Mediating;Mediator;Mentors;Mentorship;Methods;Mutation;N-Methylaspartate;neglect;Nerve Degeneration;Nervous System;Network-based;neural;neural circuit;neural network;Neurodegenerative Disorders;neuronal circuitry;neuronal excitability;Neurons;novel;Output;overexpression;Pathology;Pathway interactions;Patients;PC3 cell line;Phase;Phenotype;Physical aggression;Play;Population;postsynaptic;presynaptic;prevent;programs;protein aggregation;Reporter;Reporting;Research;research study;Resources;response;RNA Interference;Role;Senile Plaques;sex;single-cell RNA sequencing;skills;Social Behavior;Subgroup;Symptoms;Synapses;System;Systems Biology;Testing;therapeutic target;Training;Transcript;Transgenes;Transgenic Organisms;Women's study;Work

PROJECT_TITLE: Unraveling the neural basis of female aggression and dementia-related aggression: a systems biology approach.