NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Ovarian Cancer;Prevention;Rare Diseases;Women's Health Research

ORG_CITY: BALTIMORE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE Ovarian cancer is the deadliest gynecologic cancer with 80% of tumors diagnosed at a late stage though there is dras9cally higher survival for early-stage disease. This study proposes to develop novel methodologies to study the >50% of the genome comprising repeat elements in the context of ovarian tumor evolu9on and cell-free DNA, and to use genome-wide approaches to enable a non-invasive screening technology for ovarian cancer. Development of accessible screening and characteriza9on techniques for ovarian cancer has the poten9al to revolu9onize clinical prac9ce for this devasta9ng disease.

PI_NAMEs: ANNAPRAGADA, AKSHAYA VIJAYA (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Benign;Biological;Biological Assay;Biological Markers;Biology;Blood;Blood Tests;CA-125 Antigen;Cancer Detection;cancer genome;Cancerous;carcinogenesis;career;Cell Death;cell free DNA;Cells;Clinical;cost;Darkness;Data;detection assay;Development;Diagnosis;Disease;DNA;DNA Transposable Elements;Doctor of Philosophy;Early Diagnosis;Elements;Ensure;Environment;Evaluable Disease;Faculty;Failure;Future;Genome;genome-wide;genome-wide analysis;Genomics;Goals;Human;Image;insight;Length;Lesion;liquid biopsy;liver cancer model;Machine Learning;Malignant - descriptor;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of ovary;Malignant Neoplasms;Mammalian Oviducts;Mentors;Mentorship;Methodology;Methods;mortality;Movement;Nature;neoplastic cell;novel;novel strategies;Oncogenes;Outcome;Ovarian;Ovarian Mass;ovarian neoplasm;Performance;Physicians;premalignant;Prevalence;professor;protein biomarkers;Qualifying;Records;reference genome;Risk;Role;Science;screening;Screening for cancer;Screening for Ovarian Cancer;Specificity;Symptoms;Techniques;Technology;Testing;Training;transcriptome;tumor;tumor diagnosis;tumorigenesis;Unnecessary Procedures;Woman;Work

PROJECT_TITLE: Genome-wide approaches to non-invasive screening and characterization of ovarian cancers

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: SAINT LOUIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROSCIENCES

ORG_FIPS: US

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE This project seeks to understand the role of immune cells in the brain in multiple sclerosis, a central nervous system disorder with unclear causes and no cure. These immune cells, known as microglia, undergo profound changes in activity in the context of disease and have the ability to support nerves damaged by MS. Identifying how these immune cells are regulated in the context of MS may help pinpoint the causes and potential treatments for a disease that currently affects 3 million people.

PI_NAMEs: BARCLAY, KIA  (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: Ablation;Address;Adopted;Affect;Autoimmune Diseases;Biological Models;Brain;Cell Differentiation process;Cell Physiology;Cell Proliferation;Cells;Central Nervous System;Central Nervous System Diseases;Chromatin Structure;Chronic;Cognitive deficits;Communication;Cuprizone;Data;Demyelinations;design;Development;Disease;Disease associated microglia;disease model;Disease Progression;DNA cassette;Epigenetic Process;epigenetic regulation;experimental study;Faculty;Fellowship;Gene Expression;Genes;genetic signature;Genetic Transcription;Goals;histone modification;human model;Immune;Immune system;Immune Tolerance;Immunologic Memory;Incidence;Inflammation;innate immune mechanisms;insight;Institution;Label;Learning;Left;Mediating;member;Memory;Microglia;Modeling;Modification;Molecular;Morphology;Motor;mouse model;Multiple Sclerosis;multiple sclerosis patient;Mus;Myelin;Nature;nerve damage;Nerve Fibers;Nervous System Trauma;Neurodegenerative Disorders;novel;oligodendrocyte progenitor;Oligodendroglia;Oral;Pathology;Persons;Phagocytes;Phenotype;Play;Population;precursor cell;Process;programs;Recovery;Recurrence;Regulation;Relapsing-Remitting Multiple Sclerosis;remyelination;Reporter;Research;response;Role;Secondary Progressive Multiple Sclerosis;Secondary to;Sensory;Signal Transduction;skills;Specificity;targeted treatment;Techniques;Testing;Therapeutic;Therapeutic Intervention;Training;Work;Writing

PROJECT_TITLE: Examining Microglia Reactivation in Multiple Sclerosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F01A-V (20)]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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

NIH_SPENDING_CATS: Brain Disorders;Breastfeeding, Lactation and Breast Milk;Depression;HIV/AIDS;Infectious Diseases;Mental Health;Microbiome;Neurosciences;Nutrition;Pediatric;Pediatric - AIDS;Prevention;Women's Health Research

ORG_CITY: SEATTLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE An estimated 53 million children under five years of age have developmental disability with 95% of these children living in low- and middle-income countries. This project leverages data from an ongoing R01 aimed to characterize the human milk components, and infant gut microbiome, growth and neurodevelopment in Kenya. The proposed aims will address gaps in knowledge of influence of maternal factors on child neurodevelopment, with an important focus on the varying breastmilk composition by maternal factors and provide the F32 candidate with the opportunity to acquire new methods and scientific expertise and develop necessary skills to become independent researcher.

PI_NAMEs: TIWARI, RUCHI  (contact)

PROGRAM_OFFICER_NAME: RUSSO, DENISE

PROJECT_TERMS: 2 year old;5 year old;adiponectin;Adverse effects;adverse outcome;Affect;Africa South of the Sahara;Age Months;Anemia;Attention;Birth;Brain;Characteristics;Child;Cognitive;cognitive development;cognitive skill;cohort;Communication;Data;depressive symptoms;Development;Developmental Disabilities;Environment;epidemiology study;fetal;follow-up;Geographic Locations;Growth;gut bacteria;gut microbiome;HIV;HIV Infections;Human Milk;human milk oligosaccharides;human old age (65+);immunoregulation;Income;Infant;infant gut microbiome;Infection;insight;Intervention;intestinal barrier;Kenya;Knowledge;Lactation;lacto-N-neotetraose;Learning;Leptin;Link;low and middle-income countries;Maternal Age;maternal risk;Mediating;Memory;Mental Depression;Methods;microbiome;Milk;Mothers;Motor Skills;neurodevelopment;Neurodevelopmental Impairment;Neurophysiology - biologic function;nutrition;Nutritional status;Outcome;Pathogenicity;Pathway interactions;Population;post-doctoral training;postnatal period;Postpartum Period;Pregnancy;prepregnancy;prevent;Property;Publications;Research;Research Personnel;Research Project Grants;Risk;Risk Factors;Role;skills;sociodemographic factors;Statistical Methods;Stress;Training;Woman

PROJECT_TITLE: Association between adverse maternal factors and neurodevelopmental outcomes among children in Kenya

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F18-E (20)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Digestive Diseases;Genetics;Infectious Diseases;Liver Disease;Substance Misuse

ORG_CITY: LEXINGTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Chronic alcohol consumption (CHD) has been shown to poise myeloid cells towards a hyper-inflammatory phenotype and impair key pathogen defense mechanisms. Aberrant myeloid cell responses, specifically tissue- resident macrophages, have been shown to significantly contribute to the pathophysiology of CHD-induced organ damage and alcohol use disorder. Since monocytes are precursors to tissues resident macrophages, and tissue-resident macrophages in organs and organ systems affected by CHD are hard to study longitudinally, this proposal seeks to gain insight into changes that occur in complex organs subsequent to CHD by investigating the effects of repeated bouts of abstinence and post-abstinence drinking on the functional, transcriptional, metabolic, and epigenetic profiles of circulating monocytes.

PI_NAMEs: BLANTON, MADISON BROOKE (contact)

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: Abstinence;Activities of Daily Living;Address;Adult;Affect;Alcohol consumption;alcohol craving;alcohol misuse;alcohol use disorder;Alcohol-Induced Disorders;Alcoholic beverage heavy drinker;Alcoholic Liver Diseases;Alcohols;Alveolar Macrophages;anti-microbial peptide;Automobile Driving;Bacterial Infections;binge drinker;binge drinking;Biological Assay;Biological Response Modifiers;Body System;Brain;Cardiovascular Diseases;Cell Physiology;Cells;Chromatin;Chronic;chronic alcohol ingestion;Classification;Complex;Consumption;Cryopreservation;Defense Mechanisms;drinking;drinking behavior;Energy-Generating Resources;Enzyme-Linked Immunosorbent Assay;Epigenetic Process;epigenome;Ethanol;experimental study;Flow Cytometry;Functional disorder;Gene Expression Profile;Genetic;Genetic Transcription;Genus Hippocampus;Glucose Transporter;glucose uptake;Glycolysis;Glycolysis Inhibition;Heart Diseases;Heavy Drinking;histone modification;Human;Immune;Immune system;Impaired wound healing;Impairment;Incidence;Individual;Inflammatory;Inflammatory Response;insight;Knowledge;Kupffer Cells;Liver;Longitudinal Studies;Lung;Macaca mulatta;Macrophage;Malignant Neoplasms;Mediating;men;Metabolic;metabolic phenotype;Microglia;Modeling;Modification;monocyte;Myeloid Cells;National Institute on Alcohol Abuse and Alcoholism;new therapeutic target;novel;Opportunistic Infections;Organ;organ injury;Oxidative Phosphorylation;pathogen;pathogenic virus;Pathology;Pathway interactions;Peripheral;peripheral blood;Phagocytes;Phenotype;Physiological;Predisposition;preventable death;Production;Reactive Oxygen Species;Relapse;Reporting;response;Role;Self Administration;single cell ATAC-seq;single-cell RNA sequencing;Stroke;Surveys;Techniques;Testing;Therapeutic Intervention;tissue repair;Tissues;Training;transcriptome;United States;Viral;Withdrawal;Woman

PROJECT_TITLE: Uncovering the functional and mechanistic dysregulation of monocytes after abstinence and post-abstinence drinking

STUDY_SECTION_NAME: Special Emphasis Panel[ZAA1 GG (32)]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE The nervous system is composed of cell classes of varied form, function, and genetic profile, yet often these cells originate from the same population of multipotent progenitors. Here, I propose to elucidate the genetic networks regulated by the microRNA, miR9-2 and its distal enhancer, using an in vivo miR9-2 knockout mouse model which has been found to have retinal structure perturbations. This project will fill a gap in our knowledge regarding the specific role of miR9-2 in cell types of the developing retina, its function as a genetic regulator, and its potential contribution to disease.

PI_NAMEs: CALLIES, KATELYN NING LULU (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Address;Age related macular degeneration;Binding;Binding Proteins;Cell Cycle;Cell Death;cell fate specification;cell replacement therapy;cell type;Cells;Central Nervous System;Central Nervous System Diseases;Cleavage Under Targets and Release Using Nuclease;Code;Competence;conditional knockout;course development;Data;Development;Disease;Distal;Elements;Enhancers;epigenomics;Family;Family member;follow-up;Gene Expression;gene network;gene regulatory network;Gene Targeting;Genes;Genetic;Genetic Transcription;genomic locus;Genomics;Goals;Histologic;improved;in vivo;insight;Knock-out;Knockout Mice;Knowledge;Link;Machine Learning;machine learning model;macula;MicroRNAs;Modeling;mouse model;Multipotent Stem Cells;Mus;Mutagenesis;Nervous System;neurogenesis;Neurons;Pathway interactions;Pattern;Phenotype;Play;Population;Process;progenitor;programs;Proliferating;Proteins;Regulation;Regulatory Element;Repression;Research;Resolution;Retina;Retinal Diseases;retinal progenitor cell;Role;single cell ATAC-seq;single cell sequencing;single-cell RNA sequencing;Specific qualifier value;stem cell fate;stem cells;Structure;Telangiectasis;Testing;Therapeutic;Time;Tissues;Transcript;transcription factor;transcriptomics;Untranslated RNA;Visualization

PROJECT_TITLE: Control of retinal cell fate specification by the miR9-2 disease gene locus

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Transplantation

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

ORG_STATE: CA

PHR: PROJECT NARRATIVE In patients with aortic stenosis (the most common heart valve disease), imaging of the heart and aorta with Computed Tomography Angiography (CTA) allows doctors to noninvasively assess the aortic valve. The researchers propose to accurately characterize aortic stenosis by novel computerized measurements of fibrotic and calcific components of aortic valves, as well as their progression over time. They propose to further develop and validate new computerized risk scores, derived from these CTA measurements and clinical patient data using artificial intelligence, that will automatically identify the patient’s risk of suffering death or stroke, following minimally invasive transcatheter aortic valve replacement.

PI_NAMEs: DEY, DAMINI  (contact)

PROGRAM_OFFICER_NAME: EVANS, FRANK

PROJECT_TERMS: 3-Dimensional;Address;Adipose tissue;adverse outcome;Affect;aging population;Angiography;Aorta;aortic valve;aortic valve disorder;aortic valve replacement;Aortic Valve Stenosis;Appointment;Artificial Intelligence;Biological Markers;Blood Vessels;Calcium;Cardiovascular Diseases;cardiovascular imaging;Cardiovascular system;Cessation of life;Characteristics;Clinical;Clinical Data;clinical practice;clinical research site;Clinical Trials;clinically significant;Computer software;computerized;Consumption;contrast enhanced computed tomography;Coronary artery;Data;deep learning;deep learning algorithm;Disease;Disease Progression;Echocardiography;Evaluation;Event;experience;Fatty acid glycerol esters;follow-up;Future;Goals;Guidelines;healthcare burden;Heart failure;heart imaging;Heart Valve Diseases;hemodynamics;Image;Image Analysis;improved;individual patient;Inflammation;Manuals;Measurement;Measures;men;Methods;minimally invasive;Monitor;mortality;mortality risk;multi-ethnic;multidisciplinary;multimodality;Myocardium;novel;novel strategies;novel therapeutics;Obstruction;Outcome;outcome prediction;Patient observation;patient registry;Patient risk;Patients;personalized management;personalized medicine;personalized risk prediction;Pharmaceutical Preparations;Phenotype;Population;Positioning Attribute;Postoperative Period;Preventive;prognostication;prospective;radiomics;Reader;Recommendation;Research;Research Personnel;research study;Risk;Risk Assessment;risk prediction;Severities;Stroke;Symptoms;Time;Tissues;tool;Underrepresented Minority;valve replacement;vascular inflammation;Woman;Work;X-Ray Computed Tomography

PROJECT_TITLE: AI-enabled characterization of fibrocalcific aortic valve disease and inflammation from CT Angiography: Patient-specific outcome prediction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ISB-P (03)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Pancreatic Cancer;Rare Diseases

ORG_CITY: HOUSTON

ORG_NAME: METHODIST HOSPITAL RESEARCH INSTITUTE

ORG_STATE: TX

PHR: Targeting signals integral to pancreatic cancer suppressive tumor microenvironment (TME) is an unmet need and an essential goal for achieving complete and durable responses to current therapy including immunotherapy. Here, we investigate a novel mechanism by which JAG1, a pancreatic cancer worse prognostic marker, regulates the suppressive TME by impairing the anti-tumor immune response of immune cell infiltration, metabolic fitness, and function. The overarching goal of this study is to test if targeting JAG1 could overcome pancreatic cancer immunotherapy-resistance and to reinvigorate anti-tumor response.

PI_NAMEs: ZHOU, LAN  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Ablation;Acceleration;anti-tumor immune response;Antibodies;Antitumor Response;Blocking Antibodies;cancer immunotherapy;cancer initiation;cancer therapy;CD8-Positive T-Lymphocytes;Cells;Chemotherapy and/or radiation;Clinical;Coculture Techniques;Combination immunotherapy;Cytometry;cytotoxic CD8 T cells;Dendritic Cells;Dependence;Development;Disease;effector T cell;Functional disorder;Goals;Growth;Heterogeneity;Human;Immune;immune cell infiltrate;Immune checkpoint inhibitor;Immune response;Immunological Models;immunomodulatory therapies;Immunophenotyping;Immunosuppression;Immunotherapy;Impairment;Implant;improved;Infiltration;innovation;insight;Intrinsic factor;KPC model;Left;Ligands;Macrophage;Maintenance;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Melanoma;Memory;metabolic fitness;Modeling;Molecular;Molecular Target;mouse model;multiple omics;Mus;Myeloid Cells;Myeloid-derived suppressor cells;Natural Killer Cells;Neoplasm Metastasis;neoplastic cell;notch protein;novel;Organoids;pancreatic cancer model;pancreatic cancer patients;Pathway interactions;Patient-Focused Outcomes;Phenotype;Play;Population;Prognosis;Prognostic Marker;Radiation therapy;Regimen;Regulation;Resistance;response;Role;Shapes;Signal Transduction;Specimen;stem;Survival Rate;T cell infiltration;T-Cell Depletion;T-cell inflamed;T-Lymphocyte;Testing;therapy resistant;tissue resident memory T cell;transcription factor;transcriptomics;tumor;Tumor Antigens;Tumor Expansion;Tumor Immunity;tumor microenvironment;tumor progression;Tumor-Derived;tumor-immune system interactions;Work

PROJECT_TITLE: Mechanisms of JAG1-mediated immune suppression in the pancreatic cancer microenvironment

STUDY_SECTION: TIR

STUDY_SECTION_NAME: Therapeutic Immune Regulation Study Section[TIR]


ADMINISTERING_IC: AI

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: TUCSON

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative Human cytomegalovirus (HCMV) is a ubiquitous and medically significant pathogen which masterfully evades and manipulates host immune responses. As part of its life cycle, HCMV enters a quiescent state known as latency, which it accomplishes using a combination of viral and host factors. This project seeks to determine the ways HCMV manipulates the human immune system to its own advantage, to enhance viral latency and persistence.

PI_NAMEs: WHITE, TIMOTHY M (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Address;antiviral immunity;Binding;Binding Sites;Biological Assay;Biological Models;Biology;CD34 gene;Cell Physiology;Cells;cofactor;Complex;curative treatments;Cytomegalovirus;Cytomegalovirus Infections;Cytoplasm;Deubiquitination;differential expression;Disease;DNA;Dominant-Negative Mutation;Endosomes;Environment;Event;follow-up;Gene Cluster;Gene Expression;Genes;Genetic Transcription;Genome;genomic locus;global health;Goals;Hematopoietic stem cells;Herpesviridae;Homeostasis;Hour;Human;human model;human pathogen;IFNAR1 gene;Immune response;Immune signaling;Immune system;Immunity;Immunocompromised Host;Immunosuppression;in vitro Model;Infection;Innate Immune Response;insight;Integration Host Factors;interferon alpha receptor;Interferon Type I;Interferons;Investigation;Length;Licensing;Life Cycle Stages;Maintenance;Maps;Measures;Mediating;Medical;Molecular;Monitor;Morbidity - disease rate;mortality;Mutagenesis;mutant;Mutation;new therapeutic target;novel strategies;Nuclear Translocation;pathogen;Pathogenesis;Phosphorylation;Population;Positioning Attribute;Pregnancy;premature;prevent;Process;programs;Protein Dephosphorylation;Proteins;Proteomics;reactivation from latency;Receptor Activation;Receptor Signaling;recruit;Research;Response Elements;Role;Scaffolding Protein;Signal Induction;Signal Pathway;Signal Transduction;Signaling Protein;Site;Sorting;STAT1 protein;superresolution microscopy;Therapeutic;trafficking;Transcript;transcription factor;Transcription Initiation;Ubiquitin;ubiquitin isopeptidase;Viral;Viral Genes;Viral Genome;Viral Proteins;Virus;virus host interaction;Virus Latency;Virus Replication;Work

PROJECT_TITLE: HCMV stimulation of interferon signaling to promote viral gene expression and latency

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07C-Y (20)]


NIH_SPENDING_CATS: Aging;Assistive Technology;Bioengineering;Brain Disorders;Clinical Research;Neurodegenerative;Neurosciences;Parkinson's Disease;Rehabilitation

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Parkinson’s disease is often treated with medications that affect brain dopamine and with chronic deep brain stimulation, but these can result in excessive movement, known as dyskinesia. We aim to understand the brain signals related to dyskinesia in humans, and how modulation of these signals by deep brain stimulation impacts benefits and side effects of stimulation. This work will provide mechanistic insight into medication-induced and stimulation-induced beneficial and adverse effects, and may provide physiological guidance adjusting brain stimulator settings.

PI_NAMEs: OLARU, MARIA  (contact)

PROJECT_TERMS: Address;Adverse effects;Affect;Algorithms;association cortex;Basal Ganglia;Biological Markers;Bradykinesia;Brain;Chronic;Clinical;clinically relevant;cohort;Coupling;Data;Deep Brain Stimulation;Detection;Disease;Dopamine;dopaminergic neuron;Dose;Dyskinetic syndrome;Electrophysiology (science);Environment;experience;Frequencies;Globus Pallidus;Goals;Guidelines;Home;Hour;Human;Implant;insight;Intervention;Involuntary Movements;L-DOPA induced dyskinesia;Levodopa;machine learning model;Measurement;Measures;Modeling;Monitor;Motor;motor function improvement;Motor Manifestations;Movement;Nerve Degeneration;neural;Parkinson Disease;Pathologic;Patients;Pattern;Periodicals;Pharmaceutical Preparations;Physiological;Positioning Attribute;Process;Recommendation;Recording of previous events;sensor;Severities;side effect;Signal Transduction;Site;Specific qualifier value;Structure of subthalamic nucleus;Symptoms;Therapeutic;Time;Tremor;Variant;wearable device;wearable sensor technology;Work;Wrist

PROJECT_TITLE: Gamma oscillations in patients with Parkinson’s Disease using chronic invasive brain recording: detection, entrainment, and functional relevance


ORG_CITY: LITTLE ROCK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: High blood pressure, a leading cause of heart disease and the primary cause of death in the world lacks a complete understanding of its root causes and mechanisms of often-seen recurrence. Recent studies have indicated that the immune system may contribute to this rise in blood pressure, with our lab revealing immune cells interacting with kidney cells, leading to increased salt and water retention. This study aims to identify factors triggering immune cell residence in the kidney and understand their role in long-term blood pressure elevation and recurrence, offering insights for improving medications and ultimately aspiring toward a cure for hypertension.

PI_NAMEs: DECK, KATHERINE  (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: adaptive immune response;Address;Adult;American;Angiotensin II;Animals;Anti-Hypertensive Agents;Antigens;Blood Pressure;blood pressure control;blood pressure elevation;Calcium;Cardiovascular system;Cause of Death;CD8-Positive T-Lymphocytes;Cell Communication;Cell Separation;Cells;Chronic;Clinical;Complex;cytokine;Defect;Development;Distal;Diuretics;DOCA;Event;Excess Dietary Salt;Flow Cytometry;Grant;Heart Diseases;Homing;Hypertension;hypertensive;Immune;Immune system;improved;In Vitro;Individual;insight;Interferon Type II;Investigation;Kidney;kidney cell;Kidney Transplantation;Knock-out;Knockout Mice;Longevity;Mature T-Lymphocyte;Mediating;Memory;Modeling;Molecular;mortality;mouse model;Mus;Nature;Pathogenesis;Patients;Pharmaceutical Preparations;Population;prevent;Production;PTPRC gene;Purinoceptor;Recombinant Transforming Growth Factor;Recurrence;Renal Hypertension;Renal tubule structure;residence;Residencies;Role;salt sensitive hypertension;Signal Transduction;SLC12A3 gene;Sodium;Sodium Chloride;T cell therapy;T-Lymphocyte;Testing;Therapeutic;therapeutic target;Tissues;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;United States;Up-Regulation;Water

PROJECT_TITLE: Kidney-resident memory CD8+ T cells promote hypertension and memorize salt sensitivity.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-B (20)]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Digestive Diseases;Immunotherapy;Orphan Drug;Pancreatic Cancer;Radiation Oncology;Rare Diseases

ORG_CITY: STANFORD

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Narrative This proposal seeks to engineer a targeting ligand for molecularly-specific treatment via peptide targeted radionuclide therapy (PTRT) in pancreatic cancer. Spatial sequencing of human pancreatic tumors with both spatial transcriptomics and CODEX (protein) allowed us to identify claudin-4 as a promising target and we will assess peptides with high affinity for this target through preclinical studies to create both an imaging agent and therapeutic radiopharmaceutical.

PI_NAMEs: FERRARA, KATHERINE W (contact)

PROGRAM_OFFICER_NAME: CAPALA, JACEK

PROJECT_TERMS: Adenocarcinoma Cell;Affinity;Area Under Curve;Binding;Biological;cancer cell;Cancer Cluster;Cancer Etiology;Cell Culture Techniques;Cells;checkpoint inhibition;Chelating Agents;chemoradiation;chemotherapy;claudin 4;Clostridium perfringens enterotoxin;Combined Modality Therapy;Computational algorithm;Computer software;Computing Methodologies;Contracts;Cyclic Peptides;cytotoxic;Data;design;Development;Diagnosis;Diagnostic Imaging;Disease;Drug Kinetics;Engineering;Ensure;Exopeptidase;Family;Fibroblasts;Genes;Half-Life;Human;human study;Image;imaging agent;immunogenicity;Immunotherapy;improved;In Vitro;Integral Membrane Protein;Integrins;Investigation;Kidney;KRAS2 gene;Label;Laboratories;Ligands;Location;Lutetium;Machine Learning;Malignant neoplasm of pancreas;Malignant Neoplasms;Methods;Microscopy;Modeling;Molecular;Molecular Target;molecular targeted therapies;Monitor;mortality;mouse model;Mus;Mutate;nanomolar;Neoplasm Metastasis;neoplastic cell;Normal tissue morphology;older adult;overexpression;Pancreatic Adenocarcinoma;pancreatic cancer model;pancreatic cancer patients;pancreatic neoplasm;Pathway interactions;Patients;Penetration;Peptide Fragments;Peptide Hydrolases;Peptides;Periodicity;Peritoneal;Persons;Positron-Emission Tomography;pre-clinical;preclinical study;premalignant;programs;Protein Engineering;Proteins;Radiation Dose Unit;Radiolabeled;Radionuclide therapy;Radiopharmaceuticals;receptor;research clinical testing;Resistance;RHOA gene;Sampling;Site;small molecule;Specificity;Spottings;Staging;success;Tertiary Protein Structure;Therapeutic;Therapy Evaluation;Tight Junctions;Time;Tissues;tool;transcriptomics;Transgenic Mice;Transgenic Organisms;treatment response;treatment strategy;tumor;Tumor Tissue;United States;Unresectable;Update;vector;Work;Xenograft procedure

PROJECT_TITLE: Development of a theragnostic radiopharmaceutical for pancreatic cancer

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Data Science;Digestive Diseases;Genetics;Networking and Information Technology R&D (NITRD);Pancreatic Cancer;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The dismal prognosis of pancreatic adenocarcinoma (PDAC) is in large part due to >80% of newly diagnosed cases being advanced in stage. Therefore, a better understanding of the progression of PDAC could inform earlier detection and interception strategies for PDAC. Herein, we will use a multi-disciplinary approach (the BForePC Team) to develop a 3D model of PDAC progression, focusing on a unique High-Risk population who carry mutations in relevant DNA repair genes (BRCA1, BRCA2, PALB2), as a first step, to understanding this heterogenous, complex devastating disease.

PI_NAMEs: BRODY, JONATHAN ;FERTIG, ELANA ;SEARS, ROSALIE C (contact);WOOD, LAURA DELONG

PROGRAM_OFFICER_NAME: KOHAAR, INDU

PROJECT_TERMS: 3-Dimensional;Atlases;Bioinformatics;BRCA deficient;BRCA1 gene;BRCA2 gene;Cancer Center;Cancer Etiology;cancer genetics;cancer genomics;Carcinoma;Categories;cell behavior;Cell model;Cell Physiology;Cells;Cessation of life;clinical center;Clinical Pathology;cohort;Collection;Communities;Complex;Computational Biology;Computer Models;Coupling;Curative Surgery;data infrastructure;data integration;Data Science;data visualization;Death Rate;design;Detection;Development;Diagnosis;Disease;DNA Repair;DNA Repair Gene;driver mutation;dynamical evolution;early detection biomarkers;Early Diagnosis;Event;Evolution;Family;Fright;Future;General Population;Genetic;Genomic Instability;Germ Lines;Germ-Line Mutation;Guidelines;Health;high risk;high risk population;Imaging technology;improved outcome;Indiana;individual patient;Infrastructure;interdisciplinary approach;Intraepithelial Neoplasia;Lesion;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;malignant state;Maps;mathematical model;Microscopic;model development;Modeling;Molecular;molecular modeling;Molecular Profiling;Morphology;multidisciplinary;multiple omics;Mutate;Mutation;Newly Diagnosed;novel;novel marker;Oregon;Other Genetics;PALB2 gene;Pancreas;Pancreatic Adenocarcinoma;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Pancreatic Intraepithelial Neoplasia;pancreatic tumorigenesis;Pathogenicity;Patients;premalignant;Probability;Process;Prognosis;progression risk;Publishing;Quality Control;Rare Lesion;Recommendation;Recording of previous events;Registries;Research;research clinical testing;Resources;risk variant;Route;Science;screening;screening guidelines;spatiotemporal;Specimen;Surveillance Program;Survival Rate;Techniques;Technology;technology platform;Testing;Therapeutic;three-dimensional modeling;Tissues;translational impact;tumor;tumor microenvironment;United States;Universities

PROJECT_TITLE: An atlas of pancreatic tumorigenesis in the context of altered DNA repair occurring in high-risk individuals

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RTRB-U (M3)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_DEPT: CHEMISTRY

PHR: Project Narrative The GTPase RAS serves as a critical molecular switch involved in cellular signaling, with mutations driving approximately 30% of human cancers. Despite persistent efforts over four decades to target RAS, once deemed undruggable, questions surrounding the spatiotemporal regulation of RAS remain. This proposal tackles these challenges by developing and applying of chemical genetic tools, protein engineering, and chemoproteomic methods to unravel how spatiotemporal compartmentalization governs RAS-driven signaling.

PI_NAMEs: BANALES MEJIA, FERNANDO  (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Address;Affect;Apoptosis;Automobile Driving;Behavior;behavior influence;Binding;C-terminal;Cell membrane;Cell Physiology;chemical genetics;Chemicals;chemoproteomics;Chimera organism;Complex;Development;Disease;Dose;Environment;Enzymes;Epidermal Growth Factor Receptor;Exhibits;extracellular;Future;Goals;GTP Binding;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;Human;insight;Integral Membrane Protein;Kinetics;Malignant Neoplasms;Measures;Mediating;Membrane;membrane activity;Methods;migration;Molecular;mutant;Mutation;Nature;novel;Phosphorylation;Physiology;Play;Positioning Attribute;Process;Proliferating;Protein Engineering;protein oligomer;Proteins;RAS driven cancer;receptor;Receptor Protein-Tyrosine Kinases;receptor-mediated signaling;recruit;Regulation;Research;Role;Scaffolding Protein;Signal Transduction;Signaling Protein;small molecule;spatiotemporal;Specificity;synthetic biology;System;T-Cell Development;Tail;targeted treatment;tool;Transmembrane Domain

PROJECT_TITLE: Developing a Chemically-Controlled RAS Toolset

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04A-V (20)]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Prevention;Rare Diseases

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: NARRATIVE Malignant gliomas represent 60% of all CNS tumors and are responsible for about 80% of all primary malignant brain tumors; yet despite recent efforts to identify genetic and molecular risk factors for glioma progression, we still do not have predictive markers to stratify clinical outcomes. We aim to understand the molecular and cellular mechanisms at the low-grade stage that are predictive of malignant transformation by constructing a comparative spatial atlas of LGGs with distinct progression outcomes. The atlas and the computational tools will allow us to not only predict the progression outcomes of the low-grade gliomas based on the tumor microenvironment, which is applicable to clinical risk assessment and early detection, but also to suggest therapeutic targets for intervention at an early stage.

PI_NAMEs: CAI, LONG  (contact);EVERSON, RICHARD GEORGE;THOMSON, MATTHEW W.;WOLD, BARBARA J

PROGRAM_OFFICER_NAME: FU, SIDNEY WANG

PROJECT_TERMS: Affect;Architecture;Atlases;biobank;Biological Assay;Brain Neoplasms;Catalogs;Cell Communication;cell type;Cells;Central Nervous System Neoplasms;Chromosome abnormality;Chromosomes;Classification;clinical risk;Clinical stratification;cohort;Collaborations;Collection;Communities;comparative;computational pipelines;computerized data processing;computerized tools;Data;data modalities;Data Set;Diagnosis;DNA;Early Diagnosis;Early Intervention;Freezing;Gene Expression;Genes;Genetic;genomic data;Glioma;high risk;Human;Immune;immune cell infiltrate;Indolent;interoperability;Intervention;Machine Learning;machine learning model;Malignant - descriptor;Malignant Glioma;Malignant neoplasm of brain;Malignant Neoplasms;Mechanics;Messenger RNA;Methods;Minority Groups;model building;Modeling;Molecular;Molecular Analysis;mouse model;multimodality;mutant;neurosurgery;novel;Outcome;Pathway interactions;Patients;predictive marker;premalignant;preservation;prevent;Process;prospective;Proteins;Proteomics;recruit;Recurrence;Research;Resolution;Resources;Risk Assessment;Risk Factors;RNA;Role;Sampling;spatial integration;Survival Rate;Technology;therapeutic target;therapy design;Tissue Banks;Tissues;tool;Training;transcriptomics;Translations;tumor;tumor microenvironment;tumor progression;Underrepresented Minority;Visualization;Work

PROJECT_TITLE: Understanding the role of tumor microenvironment in low grade glioma progression to malignancy


NIH_SPENDING_CATS: Cancer;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

PHR: NARRATIVE Our proposal brings a unique resources and technologies to create a Pediatric Tumor Microenvironment Atlas by focusing on novel single cell spatial biology tools to identify extrinsic effects attributable to tumor microenvironment on lineage plasticity and therapy resistance of childhood solid tumors including rhabdomyosarcoma, Wilms tumor, and neuroblastoma. Through spatial transcriptomic and proteomic technologies, the project will focus on classification of immune and non-immune cells comparing diagnostic samples among responders versus non-responders, and evaluating effect of therapy on TME and lineage plasticity that could aid in identifying resistant tumor phenotype. Identification of shared TME-induced pathways and networks across pediatric solid tumors could provide insights in devising novel immunotherapy approaches that would improve outcome and reduce reliance on chemotherapies and their long-term toxic sequala in children with solid tumor cancers.

PI_NAMEs: AMATRUDA, JAMES F;ASGHARZADEH, SHAHAB  (contact);CAI, LONG

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Address;Adolescent and Young Adult;Adult;adversarial learning;Aftercare;analysis pipeline;Antibodies;Atlases;Automobile Driving;Biology;California;Cancer Biology;cancer cell;cancer therapy;causal variant;Cell Lineage;cell type;Cells;Cephalic;chemotherapy;Child;Childhood;Childhood Solid Neoplasm;Classification;Clinical;clinical research site;clinical risk;Collaborations;Communities;Complex;computational pipelines;Coupled;Cytotoxic Chemotherapy;Data;data acquisition;Data Analytics;Data Science;Development;Diagnostic;Disease;Disease-Free Survival;DNA;embryo cell;Ensure;Environment;epithelial to mesenchymal transition;ethnic diversity;Fibroblasts;Generations;Genes;Goals;high risk;Immune;Immunotherapy;improved;improved outcome;innovation;insight;Institution;Investigation;Knowledge;Lead;Los Angeles;Macrophage;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Mesenchymal;Modernization;Morbidity - disease rate;Motivation;multidisciplinary;multiple omics;Mutation;Neighborhoods;Neoplasm Metastasis;neoplastic cell;Nephroblastoma;Neuroblastoma;novel;Outcome;Pathway interactions;patient population;Patients;Pediatric Hospitals;Pediatric Neoplasm;personalized medicine;Phenotype;Population;Probability;Process;Prognosis;programs;Proteins;Proteomics;Recovery;Recurrence;Relapse;Research;Resistance;Resources;responders and non-responders;response;Rhabdomyosarcoma;risk stratification;RNA;Role;Sampling;searchable database;Solid Neoplasm;Specimen;stem;T-Lymphocyte;targeted treatment;Technology;Therapeutic;therapeutically effective;therapy resistant;Tissue Sample;tool;transcriptomics;Transforming Growth Factor beta;treatment response;tumor;Tumor Biology;tumor heterogeneity;tumor microenvironment;tumor progression;Tumor Subtype;Tumor-associated macrophages;user-friendly

PROJECT_TITLE: Pediatric Solid Tumor Microenvironment Atlas

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-K (M2)]


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Fetal Alcohol Spectrum Disorders (FASD);Intellectual and Developmental Disabilities (IDD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Substance Misuse

ORG_CITY: SAN DIEGO

ORG_DEPT: PSYCHOLOGY

ORG_NAME: SAN DIEGO STATE UNIVERSITY

PHR: Project Narrative Prenatal alcohol exposure can cause a wide range of neurocognitive, behavioral, and functional impairments that persist throughout the lifespan. However, it is unknown how the postnatal family environment influences developmental trajectories in individuals with prenatal alcohol exposure. The proposed research will use a mixed methods approach to identify postnatal risk and resilience factors in the family environment and explore the impact of these risk factors on developmental outcomes in order to inform targeted interventions that address the unique needs of children who have been prenatally exposed to alcohol and their families.

PI_NAMEs: FELICICCHIA, RILEY JORDAN (contact)

PROGRAM_OFFICER_NAME: BALACHOVA, TATIANA NIKOLAYEVNA

PROJECT_TERMS: Address;Adolescent;adverse childhood events;adverse outcome;Affect;alcohol consumption during pregnancy;Alcohol-related birth defects;Alcohol-Related Neurodevelopmental Disorder;Area;assault;Behavioral;behavioral impairment;behavioral outcome;Biological;Caregivers;Caring;Child;Clinical;Cognitive;Data;Data Analyses;Data Collection;Data Sources;Development;Developmental Process;Diagnosis;Disparity;Environment;experience;Family;Family member;Fetal Alcohol Exposure;Fetal Alcohol Spectrum Disorder;Fetal Alcohol Syndrome;foster parent;Fostering;Functional impairment;functional outcomes;grandparent;Home;Home environment;Impairment;improved;Individual;insight;Intervention;Interview;Life;Life Experience;life span;Lived experience;Measures;Methods;Neurocognitive Deficit;novel;Outcome;Parents;Population;postnatal;protective factors;Public Health;Qualitative Methods;Recording of previous events;Research;resilience;resilience factor;Risk;Risk Factors;School-Age Population;Severities;Teratogenic effects;Woman

PROJECT_TITLE: Exploring Risk and Resilience Factors in Families of Children with FASD: A Mixed Methods Approach


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Cancer;Digestive Diseases;Pancreatic Cancer;Rare Diseases

ORG_CITY: LA JOLLA

ORG_NAME: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE

PHR: PROJECT NARRATIVE Age is a major risk factor for pancreatic ductal adenocarcinoma (PDAC) with the median age at diagnosis and death being around 70 and 72 years old, respectively. It is not clear why PDAC is a disease of aging, but like other age-associated pathologies there are likely multiple variables at play. Using our preliminary data as a launching point, in this application we will develop new experimental models and decipher the mechanisms of how aging accelerates PDAC initiation and progression.

PI_NAMEs: COMMISSO, COSIMO  (contact)

PROGRAM_OFFICER_NAME: GUO, MAX

PROJECT_TERMS: Acceleration;Address;Affect;Age;age acceleration;age effect;Age Months;age related;age related changes;Age related pathologies;aged;Aging;aging mechanism;aging related disease;animal old age;Animals;Biological Assay;Biology;cancer cell;cancer diagnosis;Cancer Etiology;Cells;Cessation of life;Characteristics;Clinical;Data;Death Rate;Dependovirus;Desmoplastic;Diagnosis;Disease;Endoderm;Experimental Models;Fibroblasts;fibromodulin;Genetic Recombination;Genetically Engineered Mouse;Glean;Growth;human disease;Immune;Impact evaluation;implantation;improved;In Vitro;in vivo;Incidence;Individual;Injections;insight;KRAS oncogenesis;KRASG12D;Life;Link;Malignant Neoplasms;Modeling;mouse model;Mus;mutant;Neoplasm Metastasis;neoplastic cell;novel therapeutic intervention;old mice;Oncogenic;Outcome;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;pancreatic tumorigenesis;Patients;Persons;Phenotype;Play;Primary Neoplasm;Rejuvenation;Risk;Risk Factors;Role;Stromal Cells;Survival Rate;Testing;tool;tumor;tumor growth;tumor initiation;tumor progression;Tumor Promotion;tumorigenic;United States;Work

PROJECT_TITLE: The Aging Pancreas as a Pro-tumorigenic Niche

STUDY_SECTION: TEHM

STUDY_SECTION_NAME: Tumor Evolution, Heterogeneity and Metastasis Study Section[TEHM]


ADMINISTERING_IC: TW

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Emerging Infectious Diseases;HIV/AIDS;Health Services;Infectious Diseases;Lung;Orphan Drug;Primary Health Care;Rare Diseases;Tuberculosis

ORG_CITY: KAMPALA

ORG_COUNTRY: UGANDA

ORG_FIPS: UG

ORG_NAME: INFECTIOUS DISEASES INSTITUTE

PHR: PROJECT NARRATIVE An estimated 3 in 10 people with tuberculosis (TB)/HIV in sub-Saharan Africa have a suboptimal TB treatment outcome despite receiving effective anti-TB and anti-retroviral therapy (ART) regimens. Monthly health facility visits to collect anti-TB drugs and ART refills present several challenges due to both direct and indirect costs, resulting in poor healthcare access, continuity of care, and treatment adherence. The proposed studies will evaluate whether integrating TB treatment into community pharmacies (a well-established differentiated ART delivery model) can improve access to both anti-TB drugs and ART refills and enhance TB/HIV treatment outcomes, hence contributing to the End TB Strategy goals (zero TB deaths, zero TB infection, and zero catastrophic costs) and the UNAIDS target of ≥95% viral load suppression among people living with HIV.

PI_NAMEs: IZUDI, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: BANSAL, GEETHA PARTHASARATHY

PROJECT_TERMS: Acceleration;Address;Adherence;Africa South of the Sahara;antiretroviral therapy;Antitubercular Agents;Applications Grants;arm;Award;Behavioral Research;career;Caring;Cause of Death;Cessation of life;Clinic;Cluster randomized trial;Communities;community based treatment;Community Pharmacy;Competence;Complement;Consolidated Framework for Implementation Research;Continuity of Patient Care;cost;Data;Diagnosis;Direct Costs;Disclosure;drug distribution;Educational workshop;Effectiveness;Epidemic;Epidemiology;experience;Facilities and Administrative Costs;Feedback;Funding;Goals;Health;health care availability;Health care facility;Health system;high risk;HIV;HIV/TB;human centered design;implementation evaluation;implementation fidelity;implementation outcomes;implementation science;implementation strategy;Improve Access;improved;improved outcome;Individual;informant;Intervention;Intervention Studies;Interview;Mentors;Mentorship;Methodology;Modeling;Multi-Drug Resistance;Multidrug-Resistant Tuberculosis;Outcome;Patients;person centered;Persons;Pharmaceutical Preparations;prevent;Prevention;primary outcome;Public Health;Randomized;randomized trial;Regimen;Reporting;Research;Research Infrastructure;Research Methodology;research study;Risk;routine care;Scientist;secondary outcome;Service delivery model;Site;skills;Social Behavior;social stigma;sound;standard of care;success;Surveys;System;Testing;theories;Training;treatment adherence;treatment arm;Treatment Failure;Treatment outcome;Tuberculosis;tuberculosis drugs;tuberculosis treatment;Uganda;United States National Institutes of Health;usability;Viral Load result;Visit;World Health Organization

PROJECT_TITLE: Integrating tuberculosis treatment into community pharmacies to improve TB/HIV outcomes in Uganda.

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


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: INDIANAPOLIS

ORG_NAME: RLR VA MEDICAL CENTER

ORG_STATE: IN

PHR: PROJECT NARRATIVE Despite the close link between depression and suicide, and the high prevalence of depression in transgender Veterans, the mental healthcare utilization patterns of transgender Veterans with depression are not well understood, nor the barriers to care this population faces. This project aims to identify an approach to address barriers to mental healthcare for transgender patients with depression The objective of this proposal is consistent with VA research priorities in mental health and health equity. The lessons learned will inform efforts to improve care for transgender Veterans.

PI_NAMEs: WEINER, MICHAEL  (contact)

PROJECT_TERMS: Address;Adult;Attention;barrier to care;care seeking;Caring;cisgender;cohort;Communication;Communities;Coupled;Data;design;Development;Diagnosis;Discrimination;Disparity;efficacy testing;experience;Face;Feedback;Formulation;Fright;Funding;Future;Gender Identity;Goals;harassment;health care availability;health care service utilization;health disparity;health equity;Health Personnel;Healthcare;High Prevalence;improved;Individual;innovation;Intervention;Interview;Link;maltreatment;marginalized population;Medical Care Team;Mental Depression;Mental Health;Mental Health Services;Methodology;Methods;online community;Outcome;Patients;Pattern;perceived discrimination;Persons;Pilot Projects;Play;Population;Reporting;Research Priority;Risk Factors;Role;Secure;social media;social stigma;Source;Structure;suicidal;Suicide;suicide rate;Surveys;Technology;Testing;therapy design;transgender;Treatment Efficacy;verbal;Veterans;Work

PROJECT_TITLE: Engaging Transgender Veterans with Communication Technology

STUDY_SECTION_NAME: HSR-2 Behavioral, Social, and Cultural Determinants of Health and Care[HSR2]


ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative  The development of catalytic methods for the synthesis of complex molecules from simple building blocks ultimately impacts the efficiency and cost at which pharmaceutical drugs can be made. This proposal outlines the development and mechanistic interrogation of a new method for the synthesis of enantioenriched amine- containing compounds, which are ubiquitous motifs found in many life-saving medicines. It is anticipated that the successful execution of the proposed research will reveal a general method for the conversion of simple building blocks to valuable products, which will be of interest to practicing chemists engaged in the synthesis of bioactive molecules.

PI_NAMEs: NISTANAKI, SEPAND K (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: Acceleration;Alkenes;Amines;Anions;bioactive natural products;Carbon;Catalysis;catalyst;Cations;Chemicals;Chemistry;Complex;Computer Analysis;cost;Coupling;Development;discount;Drug Industry;experimental analysis;experimental study;functional group;Gases;Generations;Goals;Health;Human;Hydrogen Bonding;interest;ionization;Ions;Libraries;Life;Ligands;Ligation;Mediating;Medicine;metal complex;Metals;Methodology;Methods;Modeling;National Institute of General Medical Sciences;novel strategies;Pharmaceutical Preparations;Pharmacologic Substance;Preparation;pressure;Process;Property;Reaction;reaction rate;Reporting;Research;Role;screening;Source;System;Thinking;Transition Elements

PROJECT_TITLE: Stereoselective Transition Metal Catalysis Enabled by Hydrogen-Bond Donor Mediated Electrophile Activation


ADMINISTERING_IC: DA

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Drug Abuse (NIDA only);Immunization;Neurosciences;Opioid Misuse and Addiction;Opioids;Prescription Drug Misuse;Prevention;Substance Misuse;Vaccine Related

ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: PROJECT NARRATIVE Opioid use disorder (OUD) and associated overdoses are public health crises of increasing urgency in the United States, where overdose rates have skyrocketed in recent years. This F31 research proposal investigates the protection offered by a novel vaccine targeting oxycodone, a commonly abused prescription opioid. Based on the results of this research, we will inform effective vaccine design as a new treatment strategy in the face of the growing opioid epidemic.

PI_NAMEs: ROMANO, ISABELLA  (contact)

PROGRAM_OFFICER_NAME: LAO, GUIFANG

PROJECT_TERMS: American;Animal Model;Animals;Antibodies;Antibody Avidity;Antibody Response;Bacteriophages;Binding;Blood;Blood - brain barrier anatomy;blood-brain barrier crossing;booster vaccine;Brain;Carrier Proteins;Cessation of life;chemical conjugate;Clinical Trials;clinically relevant;combat;Conjugate Vaccines;cross reactivity;Data;Development;Dose;drug distribution;Drug Exposure;Drug Targeting;Effectiveness;Engineering;Enzyme-Linked Immunosorbent Assay;exposure route;Fellowship;Fentanyl;Foundations;Goals;Haptens;High Pressure Liquid Chromatography;Human;Immunization;Immunize;immunogenic;Immunology;improved;In Vitro;in vivo;Individual;interest;Intervention;Intravenous;Investigation;Keyhole Limpet Hemocyanin;Knowledge;liquid chromatography mass spectrometry;Mass Spectrum Analysis;Mediating;medication for opioid use disorder;medication-assisted treatment;Modeling;Naloxone;novel;novel strategies;novel therapeutic intervention;novel vaccines;Opioid;Opioid Antagonist;opioid epidemic;opioid overdose;Opioid Receptor;opioid use disorder;Overdose;Oxycodone;Patients;Pharmaceutical Preparations;Phase;pre-clinical;prescription opioid abuse;prevent;Prevention;protective efficacy;Public Health;Rattus;Research;Research Project Grants;Research Proposals;Route;Safety;self assembly;Serum;Severities;skills;Structure;subcutaneous;Surface;Techniques;Tetanus Toxoid;translational applications;treatment strategy;United States;Vaccinated;Vaccination;Vaccine Design;vaccine development;vaccine platform;Vaccines;vaccinology;Ventilatory Depression;Virus-like particle;Whole Body Plethysmography

PROJECT_TITLE: Bacteriophage virus-like particle based vaccines against oxycodone


NIH_SPENDING_CATS: Aging;Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Genetics;Human Genome;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Project Narrative (3 sentences) The incidences of several devastating age-related neurodegenerative diseases (NDDs) are on the rise as improved therapies for other conditions such as cancer and coronary artery disease have resulted in an aging population. Recent work has suggested that shared neuroinflammatory mechanisms play a crucial, although still somewhat unclear role in multiple NDDs. The current proposal focuses on understanding the role of the MS4A family of genes in neuroinflammatory processes in the context of amyotrophic lateral sclerosis (ALS), with the hope that this will provide mechanistic insight across a number of distinct NDDs.

PI_NAMEs: HILLER, ABIGAIL JEAN (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Address;Adult;Affect;Age;age related neurodegeneration;aging population;Alleles;ALS patients;Alzheimer's Disease;Alzheimer's disease model;American;Amyotrophic Lateral Sclerosis;Animal Model;Animals;Attenuated;Behavioral;Biological Assay;Brain;Brain Stem;Cell Death;Cells;Central Nervous System;Cessation of life;Chemoreceptors;cognitive function;Coronary Arteriosclerosis;Corticospinal Tracts;Data;Defect;Development;Diagnosis;Disease;Disease associated microglia;disease model;disease phenotype;effective therapy;Exhibits;experimental study;extend lifespan;Family;Family member;frontal lobe;Functional disorder;functional restoration;Future;Gene Cluster;Gene Expression Profile;Gene Family;Genes;Genetic Polymorphism;Genetic Transcription;genome wide association study;Gliosis;Histologic;human model;human old age (65+);Huntington Disease;Immune system;improved;in vivo;Incidence;Individual;Inflammatory;insight;interest;Knock-out;Knockout Mice;Knowledge;late life;life span;Link;Macrophage;Malignant Neoplasms;Mediating;Mediator;member;Membrane;Microglia;Motor;motor deficit;motor function improvement;motor neuron degeneration;Motor Neuron Disease;Motor Neurons;mouse genetics;mouse model;Multiple Sclerosis;Mus;Muscle Weakness;Neurodegenerative Disorders;Neuroimmune;neuroinflammation;neuron loss;novel;novel therapeutics;Parkinson Disease;Pathogenesis;Pathologic;Pathology;Pathway interactions;Phagocytosis;Phenotype;physically handicapped;Play;Population;Process;Prognosis;Property;protective allele;protein expression;Reagent;receptor;Research;response;Risk;Role;Series;sex;Single Nucleotide Polymorphism;single-cell RNA sequencing;Spinal Cord;Synapses;System;targeted treatment;Testing;therapeutic development;therapy development;transcriptomics;United States;Up-Regulation;Work

PROJECT_TITLE: Investigating the Role of MS4As in Amyotrophic Lateral Sclerosis


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Aging;Bioengineering;Dental, Oral, and Craniofacial Disease;Genetics;Osteoporosis;Regenerative Medicine

ORG_CITY: Columbus

ORG_DEPT: DENTISTRY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: NARRATIVE Defects and diseases of bones and teeth affect a large portion of the population and significantly reduce the quality of life of individuals, yet current therapies lack efficacy and predictable outcomes, therefore identification of novel factors and approaches for repair and regeneration is a critical goal. Bone sialoprotein (BSP), an extracellular matrix protein found in mineralized tissues, is important in proper skeletal and dental development. We aim to define the mechanistic functions of BSP in periodontal and skeletal development and repair and test the efficacy of BSP as a novel therapeutic for treating bone defects and injuries.

PI_NAMEs: CHAVEZ, MICHAEL B. (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: Ablation;Adult;Affect;Age;alveolar bone;Alveolar Bone Loss;Alzheimer's Disease;Arginine;Aspartate;Atomic Force Microscopy;Binding;Biological;Biological Assay;Biology;biomineralization;bone;Bone Diseases;bone fragility;bone healing;Bone Regeneration;Bone remodeling;bone repair;bone sialoprotein;C-terminal;Caring;Cell Culture Techniques;Cell Line;Cells;Cementoblast;Cephalic;Collagen;Collagen Fiber;Collagen Fibril;Collagen Type I;Complex;Connective Tissue;cost;craniofacial;CRISPR/Cas technology;Defect;Dental;Dental Cementum;Dental Implants;Dentin;Deposition;Development;Diabetes Mellitus;Disease;efficacy testing;Esthetics;Exhibits;Extracellular Matrix;Extracellular Matrix Proteins;Family;Fibrillar Collagen;Fracture;fragility fracture;Gel;Gene Expression;Genes;Genetic;Glycine;Glycoproteins;Goals;Growth;healing;Health;Heart Diseases;Histology;Human body;human old age (65+);Hydrophobicity;Hydroxyapatites;Implantation procedure;improved;In Vitro;in vivo;Individual;Injury;insight;Integrin Binding;Integrins;Joints;Knock-in;Knock-out;Knockout Mice;Knowledge;Left;Ligand Binding;Link;Location;long bone;Mastication;Mechanics;member;microCT;mineralization;Modeling;Mus;Mutant Strains Mice;Mutation;N-terminal;Natural regeneration;novel;novel therapeutics;Odontogenesis;Oral health;Osteoblasts;Osteogenesis;Osteoporosis;Outcome;Peptides;Periodontal Diseases;Periodontal Ligament;Phenotype;Physiologic calcification;Planet Earth;Play;Polyglutamic Acid;Population;Postmenopause;practical application;Premature Birth;Process;Proliferating;Proteins;Quality of life;Rattus;repaired;RGD (sequence);Role;Serum;Signal Transduction;skeletal;Skeletal Development;Skeleton;Speech;Structure;substantia spongiosa;System;Testing;Therapeutic;Time;tissue regeneration;tissue repair;Tissues;Tooth Loss;Tooth structure;Transgenic Mice;Woman

PROJECT_TITLE: Functional domains of bone sialoprotein in dentoalveolar development and healing

STUDY_SECTION: DSR

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: CLEVELAND

ORG_DEPT: PATHOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: PROJECT NARRATIVE Acute traumatic brain injury (TBI) is causally linked to chronic neurodegeneration and is the leading environmental risk factor for Alzheimer’s disease (AD), yet the reasons why are not understood. In this study, I will investigate the role of hematopoietic stem cell (HSC) dysfunction in mediating the transition from acute TBI to chronic neurodegeneration, and will examine HSC dysfunction in AD and TBI-accelerated AD. Through this research, I aim to contribute to our understanding of the pathophysiology of these neurodegenerative diseases and guide future treatments by unveiling novel therapeutic targets to counteract progressive neurodegeneration.

PI_NAMEs: CORELLA, SOFIA  (contact)

PROJECT_TERMS: Acceleration;Acute;Address;Adopted;Age Months;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Animal Experiments;Animals;Area;Automobile Driving;axonal degeneration;Blood;Blood Cell Count;Blood Cells;Bone Marrow;Brain;brain tissue;Caring;Cell Cycle;Cell Proliferation;Cells;Centers for Disease Control and Prevention (U.S.);Characteristics;Child;Chronic;clinically relevant;Data;Diffuse;disability;Disadvantaged;emotion dysregulation;Engraftment;Environmental Risk Factor;Event;experience;Experimental Designs;experimental study;fitness;Fluorouracil;Frequencies;Functional disorder;Future;Health;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hematopoietic System;Hospitalization;Immune;immune activation;immune cell infiltrate;Immune response;Immune system;Immune System Diseases;Immunohistochemistry;Impaired cognition;Impairment;Inbred C57BL Mice;Infiltration;Inflammation Mediators;inflammatory marker;Injury;injury-related death;Knowledge;Learning;Link;Measures;Mediating;men;Modeling;multimodal modeling;multimodality;Mus;Nerve Degeneration;Nervous System;Nervous System Trauma;Neurodegenerative Disorders;Neurofibrillary Tangles;neuroinflammation;Neurologic;neuron loss;new therapeutic target;novel;Organ;Outcome;Pathogenesis;Pathologic;Patients;Peripheral;Phagocytes;Phenotype;Physicians;Physiological;Play;progressive neurodegeneration;Public Health;reconstitution;Recovery;Research;Role;Scientist;Senile Plaques;stem cell exhaustion;stem cell function;Survivors;System;systemic inflammatory response;TBI Patients;Testing;Therapeutic;therapeutic target;Training;Transplantation;Traumatic Brain Injury;United States;Wild Type Mouse;Woman;Work

PROJECT_TITLE: Hematopoietic stem cell dysfunction in traumatic brain injury and Alzheimer's disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03C-K (20)]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;HIV/AIDS;Infectious Diseases;Mental Health;Mental Illness;Prevention;Primary Health Care;Social Determinants of Health;Suicide;Suicide Prevention

ORG_CITY: RONDEBOSCH

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: UNIVERSITY OF CAPE TOWN

PHR: PROJECT NARRATIVE In South Africa, people with HIV (PWH) face synergistic psychosocial and situational stressors that increase their risks for suicide and adversely affect outcomes across the HIV care continuum, including delayed antiretroviral therapy initiation, poor treatment adherence, increased risk of transmission, and lower life expectancy. This study aims to 1) explore primary healthcare-level suicide treatment practices, gaps, and needs among PWH; 2a) develop a brief behavioral intervention addressing suicide and HIV care engagement (MI-Cope-Care); 2b) refine MI-Cope-Care in an iterative, sequential pre-pilot study; and 3) evaluate the feasibility, acceptability, and preliminary effectiveness of MI-Cope-Care in a pilot randomized controlled trial. If MI-Cope-Care is found to be feasible and acceptable, it will produce the first intervention in South Africa that addresses the dual burdens of suicide and HIV, which could be further examined for effectiveness and application in other resource-constrained settings.

PI_NAMEs: RABIE, STEPHAN  (contact)

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Affect;antiretroviral therapy;Award;Behavior Therapy;behavioral clinical trial;Biometry;brief intervention;career;Caring;Cessation of life;Characteristics;Chronic;Clinic;Clinical;Clinical Trials Design;Cognitive Therapy;Communities;comorbidity;Competence;Continuity of Patient Care;coping;Coping Behavior;Coping Skills;Country;Data;Data Analyses;Diagnosis;Diagnostic;Effectiveness;effectiveness evaluation;Effectiveness of Interventions;Elements;Enrollment;Environment;experience;Face;Feedback;Feeling suicidal;Funding;General Population;Goals;health care settings;Health Care Visit;Health Personnel;Health Professional;HIV;HIV/AIDS;improved;Income;Individual;Intervention;intervention delivery;intervention mapping;Intervention Studies;Interview;K-Series Research Career Programs;Life Expectancy;Logistics;low and middle-income countries;Medical Records;Mental disorders;Mental Health;Mentors;Mentorship;Modeling;motivational enhancement therapy;Outcome;Participant;Patients;Perception;Persons;Pilot Projects;pilot trial;post intervention;Precipitating Factors;preventive intervention;Primary Care;primary care setting;Primary Health Care;primary outcome;Process;Psychiatric therapeutic procedure;Psychiatry;psychologic;Psychologist;Psychology;psychosocial;Randomized;Randomized, Controlled Trials;recruit;reducing suicide;Research;Research Personnel;Research Priority;Resource-limited setting;Resources;Risk;Risk Management;Safety;secondary outcome;skills;social determinants;South Africa;stressor;suicidal behavior;suicidal risk;Suicide;Suicide prevention;Tanzania;telehealth;Testing;therapy adherence;therapy development;Time;Training;transmission process;Trauma;treatment adherence;treatment as usual;trend;trial design;United States National Institutes of Health;Universities;Viral;Viral Load result

PROJECT_TITLE: Developing a suicide prevention intervention for people with HIV in South Africa


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human;Transplantation;Wound Healing and Care

ORG_CITY: Princeton

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative While growing fully functional skin in culture would greatly benefit a diverse array of patients, including those with severe burns, slowly healing wounds, and advanced forms of scarring alopecia, developing skin in culture with hair follicles that are correctly arranged in a spatial pattern has been particularly difficult to accomplish. Turing’s Reaction-Diffusion model has long been employed to theoretically explain periodic pattern formation; however, data from our lab has unveiled striking plasticity in hair follicle placode formation, uncovering a robust program for developing a periodic pattern. In this project, we will test the hypothesis that long-distance cell migration, rather than local signaling, serves as an underlying mechanism for hair placode induction.

PI_NAMEs: PHILLIPS, BROOKE K (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Adopted;Alopecia;Animals;Antigen-Presenting Cells;appendage;Basic Science;Behavior;beta catenin;Biology;cell motility;Cell Separation;cell type;Cells;Chemotaxis;Cicatrix;Clinical;Collaborations;Coupled;Cre lox recombination system;Cues;Data;design;Development;Developmental Biology;Diffusion;Embryo;Embryonic Development;Ensure;Environment;epidermal stem cell;Epithelium;experimental study;Family;Feathers;FGF20 gene;Foundations;Genes;Goals;Grant;Growth;Hair;Hair follicle structure;Image;inhibitor;keratinocyte;Knock-out;Knowledge;Ligands;Mediating;Medical;Medicine;Mentorship;migration;Modeling;Molecular;Monitor;Morphogenesis;mosaic;mouse model;Mus;novel strategies;Output;P-Cadherin;Pathway interactions;Patients;Pattern;Pattern Formation;Periodicals;programs;promoter;Reaction;Regenerative Medicine;Reporter;Resources;Sampling;self organization;severe burns;Signal Transduction;Skin;Skin graft;skin organogenesis;Skin Transplantation;Specific qualifier value;stem cell derived tissues;Structure;Suggestion;Sweat Glands;System;Testing;Time;Tissue Transplantation;Tissues;Training;transcription factor;Undifferentiated;Universities;WNT Signaling Pathway;Wood material;Work;wound healing

PROJECT_TITLE: Investigating the Mechanism of Hair Follicle Placode Induction : A novel approach to understanding establishment of the periodic pattern

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-Q (20)]


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Over 60% of T cell acute lymphoblastic leukemias (T-ALLs) harbor mutations in the NOTCH1 signaling pathway; however, pan-Notch inhibitors are associated with significant toxicities. We previously showed that the lymphoid- restricted transcription factor ETS1 is essential for Notch-activated T-ALL survival, but not essential for overall health. Here, we propose a study to define the downstream oncogenic pathways and cis-regulatory elements of ETS1 in T-ALL, which may lead to new anti-leukemic strategies without intolerable toxicities.

PI_NAMEs: LIN, KARENA HSIJAN (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Acute Lymphocytic Leukemia;Acute T Cell Leukemia;acute T-cell lymphoblastic leukemia cell;Binding;Binding Sites;candidate validation;Cell Line;Cell Survival;chemotherapy;Chromatin;Chromatin Loop;Clinical Trials;CRISPR interference;Data;Dependence;Development;Disabling;Dose Limiting;Downstream Enhancer;Elements;Enhancers;ETS1 gene;gamma secretase;gastrointestinal;Genes;Genetic;Genetic Transcription;genome wide screen;genome-wide;Growth;Guanine Nucleotide Exchange Factors;Health;Histones;Human;Impairment;In Vitro;in vivo;inhibitor;Knowledge;leukemia;leukemia treatment;leukemogenesis;Lymphoid;mouse model;Mus;Mutation;Names;notch protein;Notch Signaling Pathway;NOTCH1 gene;novel;Oncogenes;Oncogenic;overexpression;Pathway interactions;patient derived xenograft model;Patients;Play;postnatal;Probability;programs;Regulation;Regulatory Element;Relapse;Repression;response;Role;Signal Pathway;Site;Survival Rate;T-Cell Activation;T-Cell Development;T-Lymphocyte;targeted treatment;Testing;Toxic effect;transcription factor;tumor

PROJECT_TITLE: Defining the genetic mechanisms of ETS1 dependency in Notch-activated T Cell Acute Lymphoblastic Leukemia (T-ALL)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

PHR: PROJECT NARRATIVE Glioblastoma (GBM) is a highly malignant primary brain tumor and with a median survival of 15 months despite aggressive surgical and chemotherapeutic interventions. Glioblastoma stem-like cells (GSCs) are the key cells responsible for initiating this tumor and they can adapt to the complex environment in the brain, even areas of low oxygen. This project will help us develop a deeper understanding of GSC biology, especially the tools of translation regulation (mRNA-to-protein), as they are corrupted for use in stressful low-oxygen conditions thereby revealing a novel list of targets for future therapy in GBM patients.

PI_NAMEs: DASHORA, HIMANSHU RAJEEV (contact)

PROJECT_TERMS: Adaptive Behaviors;Address;Adult;Affect;angiogenesis;Area;Behavior;behavioral response;Bioinformatics;Biological;biological adaptation to stress;Blood Vessels;Brain;Brain Neoplasms;cancer cell;Candidate Disease Gene;Cell Culture Techniques;Cell Line;Cell Maintenance;Cell Physiology;Cell Survival;Cells;Cellular biology;Cellular Stress;Central Nervous System Neoplasms;Characteristics;chemoradiation;chemotherapy;Complex;Data;DNA;Down-Regulation;effective therapy;Environment;Epigenetic Process;Excision;Experimental Designs;experimental study;Future;GCN2 protein kinase;Gene Expression Regulation;gene network;Gene Silencing;Genes;genetic information;Genetic Transcription;Glioblastoma;Glioma;Heterogeneity;Human;Hypoxia;Impairment;improved;in vivo;insight;Invaded;knock-down;Knowledge;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Measures;Mediating;member;Messenger RNA;Metabolic Pathway;mouse model;Mus;nerve stem cell;Neuroglia;novel;Operative Surgical Procedures;Outcome;Oxygen;Pathway interactions;Patient Care;patient derived xenograft model;Patient-Focused Outcomes;Patients;Post-Transcriptional Regulation;precision medicine;pressure;Primary Brain Neoplasms;programs;Proliferating;Property;Protein Biosynthesis;Proteins;Radiation therapy;Recurrence;Regulation;Research;Ribosomal RNA;ribosome profiling;Role;Sampling;self-renewal;small hairpin RNA;stem cells;stem-like cell;stemness;Techniques;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;therapy resistant;Tissues;tool;Transcript;transcriptome sequencing;Translational Regulation;Translational Repression;Translations;treatment strategy;tumor;tumor behavior;tumor growth;tumor initiation;Tumor Promotion;tumor xenograft;Tumorigenicity;virtual;Work

PROJECT_TITLE: Translation Regulation Contributes to Hypoxia Adaptation in Glioblastoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09B-C (20)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Kidney Disease;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative Copy number variations (CNVs) of Apolipoprotein L1 (APOL1) are associated with nondiabetic kidney diseases, albeit the allelic architecture of the APOL1 kidney disease risk variants within CNVs remains unclear. Our studies aim to discriminate the non-risk and risk variant copies within APOL1 CNVs and determine the functional consequences of APOL1 CNVs. This research will provide insights into risk variant dosage mechanisms of APOL1 CNVs as a driver for the phenotypic variability observed in APOL1-associated nondiabetic kidney diseases in African Americans.

PI_NAMEs: SIMEONE, CHRISTOPHER A (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Address;African American population;Alleles;Allelic Imbalance;Amino Acid Substitution;Amino Acids;Apolipoproteins;Architecture;Automobile Driving;Biological Assay;Black race;career;Cell Death;Cell Survival;Cells;Code;cohort;Collaborations;Complex;computerized tools;congenital anomalies of the kidney;Copy Number Polymorphism;cytotoxicity;Data;Data Set;design;Detection;Development;Discrimination;Disease;Disease susceptibility;disorder risk;dosage;Dose;educational atmosphere;End stage renal failure;Event;Exons;experimental study;Family;Fellowship;Focal and Segmental Glomerulosclerosis;Foundations;Functional disorder;Future;Gene Dosage;Gene Duplication;gene function;Genes;Genetic;Genetic Predisposition to Disease;genome sequencing;Genomics;Genotype;Goals;Heterogeneity;Heterozygote;high risk;Home;Human Genome;Human Herpesvirus 4;Hypertension;IGA Glomerulonephritis;In Vitro;Individual;Injury to Kidney;insight;Institution;Interferon Type II;Interferons;Investigation;Israel;Kidney;Kidney Diseases;Kidney Failure;Knowledge;Laboratories;Link;Mediating;Medical center;medical schools;member;Mentorship;mouse model;Nephronophthisis;non-diabetic;Patients;Phenotype;Population;population based;Predisposition;Principal Investigator;Proteinuria;Recurrence;Research;Research Personnel;response;Risk;Risk Assessment;risk variant;Role;Structure;Study Skills;Techniques;Training;Transcript;transcriptome sequencing;transcriptomics;transforming virus;Untranslated RNA;Urinary tract;Variant;whole genome;Work

PROJECT_TITLE: The Impact of APOL1 Copy Number Variation on Kidney Disjavascript:autoSave('https://apps.era.nih.gov:443/gmii/home.era?menu_itemPath=59%27)ease Susceptibility in African Americans

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Fellowships in Kidney, Urology, and Hematology[DDK-G]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE There are numerous retinal and systemic conditions that negatively impact the development of the fovea, a specialized anatomical region of the retina that supports high-acuity vision. This project aims to investigate structural and functional specializations of the fovea, including one such condition, using a combination of clinical and research-grade non-invasive ocular imaging tools. The training environment is particularly suited to support my interests in translational research and my development into a successful, independent vision scientist.

PI_NAMEs: KREIS, JOSEPH G (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Abbreviations;absorption;achromatopsia;adaptive optics;Affect;Albinism;Angiography;Area;blue cone monochromacy;career;Caring;Cells;Clinical;clinical application;Clinical assessments;clinical imaging;Clinical Research;Collaborations;Cone;Contrast Sensitivity;Data;density;Development;Diameter;Disease;Engineering;Environment;experience;Eye;Fellowship;Foundations;fovea centralis;Functional Imaging;ganglion cell;Goals;Health;Histologic;Human;Image;Imaging Device;Imaging Techniques;improved;in vivo;in vivo imaging;Individual;Injury;insight;Interdisciplinary Study;interest;Investigation;Knowledge;Laboratories;Lead;Light;Maps;Measures;Mediating;meter;Methods;Modality;Morphology;mosaic;Neurobiology;non-invasive imaging;ocular imaging;Ophthalmoscopy;Optical Coherence Tomography;Optics;Pathology;Perimetry;Photons;Photoreceptors;Pigments;Positioning Attribute;premature;Premature Birth;Privatization;Process;Psychophysics;Publishing;Recording of previous events;Regional Anatomy;Reporting;Research;Research Project Grants;Resolution;Retina;Retinal Cone;Retinal Diseases;Retinal Ganglion Cells;retinal imaging;retinal rods;Rod;Scanning;Scientist;Scotoma;statistics;structural imaging;Structure;Structure-Activity Relationship;Technology;Testing;Thick;Tissues;tool;Training;training opportunity;Translational Research;translational scientist;Variant;Vertebrate Photoreceptors;Vision;vision science;Visual;Visual Acuity;visual dysfunction;Work

PROJECT_TITLE: Assessing Foveal Specializations in Health and Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03B-L (20)]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: HADLEY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: RELEVANCE (See instructions): mR NA in cells contains base modifications, strategically (and dynamically) placed at specific position in the RNA. The proposed research will develop a novel system to generate RNA with (multiple and different) modified bases incorporated site-specifically. This capability will allow new studies to dramatically expand our understanding of base modifications in specific genes throughout biology.

PI_NAMEs: MARTIN, CRAIG T (contact)

PROGRAM_OFFICER_NAME: NOVA, IAN CURTIS

PROJECT_TERMS: Alternative Splicing;base;Biology;Cells;chemical synthesis;Environment;Fluorescence Resonance Energy Transfer;Fluorescent Probes;fundamental research;Future;Genes;Genetic Transcription;Immobilization;Instruction;Label;Length;Measurement;Messenger RNA;Modification;novel;Play;Positioning Attribute;Research;RNA;RNA chemical synthesis;Role;Site;stable isotope;Structure;System;therapeutic RNA;Translations

PROJECT_TITLE: MFB: Fluidics system for efficient site-specific labeling of RNAs

STUDY_SECTION_NAME: Special Emphasis Panel[ZHG1 HGR-P (J3)]


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

PHR: PROJECT NARRATIVE Recent surveys in the United States reveal that the fear of developing Alzheimer's disease (AD) has now surpassed the fear of developing cancer. This is undoubtedly related to the lack of effective medications for AD, which is due to the large gap in our scientific understanding of the problem. I seek to tackle this problem by investigating the novel pathophysiologic role of neuronal primary cilia deterioration in AD.

PI_NAMEs: MILLER, EMIKO L (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: abeta accumulation;Acceleration;Address;Adenylate Cyclase;Affect;Age;age related;Aging;aging related disease;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease patient;Amyloid;Amyloid beta-Protein;Amyloid beta-Protein Precursor;amyloid pathology;amyloid precursor protein processing;Autopsy;Binding;Biological Assay;Biometry;Brain;brain control;brain health;Brain Mass;career;Cells;Cilia;Clinical;Co-Immunoprecipitations;Cognition;Deletion Mutation;Dementia;Deterioration;differential expression;Disease Progression;effective therapy;Electron Microscopy;Engineering;Environment;extend lifespan;extracellular;Fright;Functional disorder;functional loss;Genes;Goals;High Prevalence;Hippocampus;Human;Immunofluorescence Microscopy;Immunohistochemistry;Impaired cognition;Impairment;In Vitro;in vitro Model;in vivo;Incidence;insight;Investigation;Kinetics;Label;Length;Life Expectancy;Link;Maintenance;Malignant Neoplasms;mouse model;Mus;Mutate;Mutation;Neurons;new therapeutic target;novel;Organelles;Pathogenicity;Pathologic;Pathology;Pharmaceutical Preparations;Phenotype;Play;Population;Positioning Attribute;pre-clinical;Prevalence;Prevention;Process;Property;Proteins;Recombinants;Recovery;Research;Role;sarkosyl;Senile Plaques;Sensory;Signal Transduction;Structure;Surveys;Techniques;Testing;Training;United States;Work

PROJECT_TITLE: The Role of Neuronal Primary Cilia Deterioration in Alzheimer's Disease


NIH_SPENDING_CATS: Pediatric;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

PHR: PROJECT NARRATIVE Mammalian embryogenesis is a robust process with numerous checkpoints and corrective processes in place to ensure proper development. The proposed project sets forth to examine how morphogenesis regulates cell cycle remodeling during early postimplantation development and identify how this paradigm may contribute to cell number regulation in the mammalian embryo. Increased understanding of the details of developmental transitions in normal and perturbed conditions will reveal novel insight into the mechanisms regulating developmental robustness in mammalian embryos.

PI_NAMEs: BERNYS, ALANA CATHERINE (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Acceleration;Apical;Apoptosis;Basement membrane;Biological Assay;cell behavior;Cell Count;Cell Cycle;Cell Cycle Progression;Cell Cycle Regulation;Cells;Collagen;Communication;Conceptus;Data Analyses;Defect;design;Development;Developmental Biology;Educational workshop;Embryo;embryo cell;Embryology;Embryonic Development;embryonic stem cell;Ensure;Environment;Epiblast;Epithelium;ex vivo imaging;Exhibits;Exposure to;G1/S Transition;G2/M Transition;Genetic Engineering;Goals;Growth;Image;Impairment;Implant;implantation;Individual;insight;Integrins;Investigation;Link;Maintenance;Mammals;Manuscripts;Measurement;Membrane;Methods;migration;Molecular Probes;Morphogenesis;Mus;natural Blastocyst Implantation;novel;Nuclear;outreach;Phase;preimplantation;prevent;Process;Proliferating;Regulation;Reporter;Research Personnel;Resistance;Role;Sampling;Science;self organization;Shapes;Signal Transduction;Site;skills;stem cell model;success;Surface;System;Testing;Time;Tissues;Training;Universities;Uterus;Work;Writing

PROJECT_TITLE: Mechanisms of cell cycle regulation in embryos of normal and unusual size

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Project Narrative Mutation to WW-domain containing adapter with coiled-coil (WAC), an adapter in the deposition of histone H2B ubiquitination (H2Bub), leads to DeSanto-Shinawi Syndrome, a neurodevelopmental disorder with autism-like characteristics. The proposed studies will leverage genomic and behavioral analyses to define the role of WAC in H2Bub-dependent gene regulation in neurons, exploring the hypothesis that WAC facilitates proper neuronal activity-dependent transcription. This work will establish H2Bub as a novel epigenetic regulator of neuronal activity and provide insight into the molecular etiology of neurodevelopmental disorders driven by dysfunction of H2Bub regulators.

PI_NAMEs: ERICKSON, ALYSSA A (contact)

PROGRAM_OFFICER_NAME: KIM, JENNY LILY

PROJECT_TERMS: Adaptor Signaling Protein;Affect;autism spectrum disorder;Behavioral;Behavioral Paradigm;Binding;Biology;Brain;brain dysfunction;career;Characteristics;Chromatin;Complex;conditioned fear;Deposition;Development;Developmental Delay Disorders;Disease;Epigenetic Process;epigenomics;Etiology;Face;Functional disorder;Gene Expression;Gene Expression Regulation;gene function;Genes;genetic regulatory protein;Genetic study;Genetic Transcription;Genome;genome sequencing;Genomics;Goals;Heterozygote;Hippocampus;Histone H2B;Histones;Homeostasis;Human Genetics;in vivo;in vivo Model;individuals with autism spectrum disorder;insight;Intellectual functioning disability;Investigation;knock-down;Knock-out;Learning;Link;Loss of Heterozygosity;Lysine;Memory;Modeling;Modification;Molecular;molecular pathology;Monoubiquitination;morris water maze;mouse model;Mus;Mutation;Nervous System;neural;Neurocognitive;neurodevelopment;Neurodevelopmental Disorder;Neurologic;Neurons;Neurosciences;novel;object recognition;Pathology;Pathway interactions;Pattern;Performance;Phenotype;Principal Investigator;programs;recruit;Regulation;Research;response;RNA Polymerase II;Role;Short-Term Memory;Stimulus;Structure;Symptoms;Synapses;Syndrome;System;Testing;Therapeutic;Training;Transcriptional Regulation;transcriptome;transcriptome sequencing;ubiquitin-protein ligase;Ubiquitination;Variant;Work

PROJECT_TITLE: Understanding the Role of Histone Ubiquitination in Plasticity and Neurodevelopmental Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03A-E (20)]


FUNDING_MECHANISM: OTHERS

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Data Science;Hematology;Networking and Information Technology R&D (NITRD);Orphan Drug;Rare Diseases;Sickle Cell Disease

ORG_CITY: RESEARCH TRIANGLE PARK

ORG_NAME: RESEARCH TRIANGLE INSTITUTE

ORG_STATE: NC

PI_NAMEs: KRONER, BARBARA L (contact)

PROGRAM_OFFICER_NAME: MONDORO, TRACI

PROJECT_TERMS: Advanced Development;Area;Clinical Trials;Common Data Element;Data;Data Collection;data harmonization;data interoperability;data management;data registry;data repository;data resource;data sharing;Data Sources;data standards;Dedications;Development;experience;federated data;gene therapy;Goals;Human;Human Resources;improved;Individual;Infant;innovation;Interdisciplinary Study;International;Knowledge;Leadership;National Heart, Lung, and Blood Institute;patient registry;Patients;programs;Provider;Registries;repository;Research Institute;Research Personnel;Resources;Sickle Cell;Sickle Cell Anemia;United States

PROJECT_TITLE: CURE SICKLE CELL INITIATIVE DATA STRATEGY AND DATA RESOURCES PROGRAM


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

ORG_CITY: BALTIMORE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Project Narrative CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) patients often experience strokes and cognitive impairment, and while disease causing mutations in the protein NOTCH3 have been studied deeply in brain blood vessels, a key cell type that envelops brain blood vessels known as the pericyte is virtually unstudied in this disease despite ample NOTCH3 presence. The goal of this proposal is to improve our understanding of pericyte contributions to early brain blood flow deficits seen in this disease as pericytes contribute to multiple blood flow control mechanisms. Determining the role that pericytes play in disease progression can lead to identification of targets for early therapeutic intervention.

PI_NAMEs: VIGDERMAN, ABIGAIL SHIRA (contact)

PROJECT_TERMS: Animals;Arterial Disorder;arteriole;autosome;awake;Bathing;Blood capillaries;Blood flow;Blood Vessels;Brain;Brain Diseases;brain parenchyma;brain pericytes;Calcium;Calcium Channel;Calcium Channel Blockers;Calcium Signaling;Cell membrane;cell type;Cells;Cephalic;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular system;Cerebrum;Clinical;Communication;comparison control;Contracts;Data;Development;Diameter;Disease;disease phenotype;Disease Progression;disease-causing mutation;Electron Microscopy;Electrophysiology (science);Endothelial Cells;Erythrocytes;Exhibits;experience;Fellowship;Fluorescence;Functional disorder;Future;Gap Junctions;Goals;Head;Hyperactivity;Image;Impaired cognition;Impairment;improved;Injections;Inositol;insight;Institution;Intervention;ITPR1 gene;L-Type Calcium Channels;Laser Scanning Microscopy;Measures;Mediating;Membrane;Membrane Potentials;Methodology;Microelectrodes;microscopic imaging;Microvascular Dysfunction;Morphology;mouse model;Mus;Mutate;Mutation;NOTCH3 gene;novel;optogenetics;parenchymal arterioles;Pathogenesis;Pathogenicity;Pathology;Patients;Penetration;Pericytes;pharmacologic;Physiology;Play;Positioning Attribute;Preparation;pressure;prevent;Proteins;receptor;Relaxation;Research Personnel;response;restraint;Role;Signal Transduction;Site;Slice;Smooth Muscle Myocytes;Stroke;Subcortical Infarctions;Subcortical Leukoencephalopathy;success;Therapeutic Intervention;Training;Transgenic Mice;Transgenic Organisms;Trees;tripolyphosphate;two-photon;Vascular Cognitive Impairment;Vibrissae;virtual;voltage;Work

PROJECT_TITLE: Contractile Pericyte-Mediated Cerebrovascular Deficits in a Mouse Model of CADASIL


NIH_SPENDING_CATS: Arthritis;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Machine Learning and Artificial Intelligence;Neurosciences;Patient Safety;Physical Injury - Accidents and Adverse Effects;Rehabilitation

ORG_CITY: PROVIDENCE

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE A new ligament surgery that stimulates the anterior cruciate ligament (ACL) to heal has shown promise in reducing post-surgical posttraumatic osteoarthritis. We believe the reason behind this is that the new surgery restores the native ACL and its neural elements that normally provide information about joint function to the central nervous system, while conventional surgery does not. The parent randomized clinical trial will tell us whether the new surgery is at least as good as the conventional one, and the ancillary study will tell us whether, and how, the new surgery restores muscle and joint function.

PI_NAMEs: BEVERIDGE, JILLIAN ELIZABETH (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Address;Age;Anatomy;Ancillary Study;Animals;Anterior;Anterior Cruciate Ligament;anterior cruciate ligament injury;anterior cruciate ligament reconstruction;anterior cruciate ligament rupture;Athletic;Basic Science;Binomial Distribution;Blood coagulation;bone;Cartilage;Central Nervous System;Classification;Clinical Research;Clinical Trials;clinically relevant;Communication;Communities;Control Groups;Conventional Surgery;Coupled;Cross-Sectional Studies;Data;Decision Making;demographics;Electromyography;Elements;Enrollment;Excision;Extracellular Matrix;follow-up;Functional disorder;functional outcomes;Future;hamstring;healing;Health;high risk;Hospitals;imaging study;Implant;Individual;Inferior;Injury;innovation;joint function;Joint Laxity;Joints;kinematics;Knee;Leg;Length;ligament injury;Ligaments;Linear Models;Longitudinal Studies;Lower Extremity;Machine Learning;machine learning classification;Measurement;Mechanics;Mechanoreceptors;Motion;Muscle;Muscle function;muscle strength;neural;neuromuscular;neuromuscular activity;neuromuscular function;novel;Operative Surgical Procedures;Outcome;Parents;Participant;participant enrollment;Patient Outcomes Assessments;Patient Participation;Patients;Pattern;Phase;Positioning Attribute;pre-clinical;preservation;Procedures;randomized, clinical trials;Randomized, Controlled Trials;Reconstructive Surgical Procedures;Recovery;recruit;Regression Analysis;Research;Research Design;response;restoration;Rhode Island;Risk;Risk Factors;Sample Size;scaffold;sex;Signal Pathway;Site;standard of care;Structure;support vector machine;Surface;Techniques;tendon graft;Testing;tibia;Time;Traumatic Arthropathy;trial comparing;vector;Visit;young adult

PROJECT_TITLE: Neuromuscular response to competing ACL surgeries

STUDY_SECTION_NAME: Special Emphasis Panel[ZAR1 AJ (M1)]


ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE Recently, we have demonstrated that patients with heart failure have decreased acyl-carnitines in heart biopsies as compared to controls, but still have normal (HFpEF) or increased (HFrEF) acyl-carnitines in the blood. This project tests the hypothesis that extracellular acyl-carnitines are taken up and oxidized by cardiomyocytes and intact hearts, that this rises under hemodynamic or metabolic stress, and is impaired by reduced transporters in HF. Understanding how extracellular acyl-carnitines are (or are not) utilized in the normal heart, and hearts under acute or chronic stress could lead to better strategies to metabolically counter heart failure.

PI_NAMEs: MULLIGAN, ABIGAIL S. (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: Acute;acute stress;acylcarnitine;Address;Adipocytes;Adult;aorta constriction;ATP Synthesis Pathway;Basic Science;Binding;Bioinformatics;Biopsy;Blood;Blood Circulation;Carbon;Carbon Dioxide;Cardiac;Cardiac Myocytes;Cardiovascular system;Carnitine;Carnitine Palmitoyltransferase I;CD36 gene;Cell membrane;Cell Respiration;Cells;Cellular Stress;Cessation of life;Chronic;Chronic stress;Citric Acid Cycle;cohort;comparison control;Consumption;Cytoplasm;Data;design;diet-induced obesity;Disease;Disparity;Educational process of instructing;EFRAC;Epidemic;extracellular;fatty acid oxidation;flexibility;Functional disorder;Generations;Genetic;genetic manipulation;Goals;Harvest;Heart;Heart failure;heart function;heart metabolism;hemodynamics;High Fat Diet;Homeostasis;Human;Impairment;improved;In Vitro;in vitro testing;in vivo;Incidence;insight;interest;ischemic injury;Label;Link;Liver;long chain fatty acid;loss of function;Measures;Medical;Membrane Transport Proteins;Metabolic;Metabolic stress;Metabolic syndrome;Metabolism;metabolomics;Mitochondria;Modeling;Molecular;Morbid Obesity;mouse model;Mus;Muscle;Muscle Cells;Myocardial;Myocardium;Neonatal;Nonesterified Fatty Acids;Obesity;Oleic Acids;Organ;oxidation;Oxidative Phosphorylation;Palmitic Acids;Palmitoylcarnitine;Patients;pharmacologic;Phenotype;Plasma;Play;Positioning Attribute;preservation;pressure;Primary Cell Cultures;Process;protein expression;Proteins;Radiolabeled;Rattus;Research;Role;Scientist;Skeletal Muscle;skills;Stress;Testing;Thermogenesis;Training;United States;uptake;Ventricular;Wild Type Mouse;Work;Workload

PROJECT_TITLE: Role of Extracellular Long-Chain Acyl-carnitines in the Normal and Stressed Heart

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-R (20)]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Clinical Research;Neurosciences

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: PROJECT NARRATIVE The proposed research will reveal how the brain integrates information about speech over time, both in silence and in the presence of background noise. The results of these experiments will further our knowledge of the computations that enable speech recognition in noisy real-world conditions, as well as how auditory cortex flexibly adapts to changing environments. Answering these questions is a critical step towards understanding the deficits in listening in noise that are present in auditory neurodevelopmental and attentional disorders.

PI_NAMEs: BOEBINGER, DANA  (contact)

PROGRAM_OFFICER_NAME: SCHURMAN, JACLYN REBECCA

PROJECT_TITLE: The impact of noise on temporal integration of speech in the human brain

STUDY_SECTION_NAME: Special Emphasis Panel[ZDC1 SRB-K (13)]