NIH_SPENDING_CATS: Aging;Biotechnology;Childhood Obesity;Clinical Research;Genetics;Human Genome;Mental Health;Nutrition;Obesity;Pediatric;Precision Medicine;Prevention

ORG_CITY: SAINT LOUIS

ORG_DEPT: PSYCHIATRY

ORG_NAME: WASHINGTON UNIVERSITY

PHR: PROJECT NARRATIVE Antipsychotic treatment, which is known to cause differential age-related weight gain and related cardiometabolic risk (CMR) conditions in mentally ill populations, is an optimal example of how precision medicine approaches could rapidly impact treatment outcomes. This proposal leverages the existence of large population-based studies and hospital-based biobanks with randomized clinical trial data from studies funded by NIH, PCORI and pharma, and will apply genomics and novel molecular techniques, including array-based genotyping, CRISPR screening and cellular functional studies to understand the genetic risk for and mechanisms underlying antipsychotic-induced weight gain and associated CMR, from childhood to older adulthood. If funded, this project will substantially contribute to the understanding of mechanisms of accelerated aging associated with weight gain, and the development of an analytic algorithm that will eventually be able to predict and prevent antipsychotic-related weight gain.

PI_NAMEs: JUSTICE, ANNE ;NICOL, GINGER E (contact)

PROGRAM_OFFICER_NAME: EVANS, JOVIER D

PROJECT_TERMS: Acceleration;Address;Adipocytes;Adult;Affect;Age;age acceleration;age difference;age related;Aging;aging related;Algorithms;Antipsychotic Agents;biobank;Bioinformatics;Biological;Biological Assay;Biological Markers;Body Composition;Body fat;Body mass index;Body measure procedure;Candidate Disease Gene;cardiometabolic risk;Cardiovascular Diseases;causal variant;Cell Aging;Cell Line;Cell Physiology;cell type;Cells;Cellular Assay;Cellular biology;Characteristics;Child;Childhood;Chromatin;Clinical;Clinical Data;Clinical Trials Design;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Cohort Studies;Collection;CRISPR interference;CRISPR screen;CRISPR-mediated transcriptional activation;CRISPR/Cas technology;Data;Data Set;Decision Making;Development;disorder risk;diverse data;drug development;Drug Exposure;Drug Targeting;Engineering;epidemiology study;Fatty acid glycerol esters;Funding;Future;gene discovery;Gene Expression;General Population;Generations;Genes;Genetic;genetic association;Genetic Determinism;Genetic Risk;genetic variant;Genetic Variation;genome wide association study;genome wide screen;genomic locus;Genomic Segment;Genomics;Genotype;Geriatric Psychiatry;Hospitals;Human;in silico;In Vitro;Individual;induced pluripotent stem cell;Industry;insight;insulin sensitivity;Letters;life span;Link;Lipids;Measures;Mediating;Mental disorders;Mentally Ill Persons;Meta-Analysis;Metabolic;Metabolic Diseases;metabolic phenotype;Methods;Methylation;middle age;Modeling;Molecular;molecular phenotype;Molecular Target;mortality;multiple omics;Neurons;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Obesity;older adult;older patient;Pathway interactions;Pattern;Pharmaceutical Preparations;Pharmacological Treatment;phenotypic data;Physiological;polygenic risk score;Population;population based;population health;Population Study;precision medicine;predictive modeling;Premature Mortality;prevent;psychogenetics;Public Health;randomized, clinical trials;Research;response;Risk;Sampling;Screening Result;secondary analysis;Selection for Treatments;side effect;Source;Techniques;Testing;Tissues;tool;Treatment outcome;treatment response;treatment risk;United States National Institutes of Health;Validation;Variant;variant of interest;Weight;Weight Gain;Youth

PROJECT_TITLE: Discovery and CRISPR validation of genetic factors associated with antipsychotic-induced weight gain and cardiometabolic risk

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-F(02)]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: NEW HAVEN

ORG_COUNTRY: UNITED STATES

ORG_DEPT: CHEMISTRY

ORG_FIPS: US

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative: The control of protein function by modulation of its structure and dynamics is of significant therapeutic benefit to human health. One of the hurdles to such control is a more complete understanding of how different regions in a protein architecture interact with one another. This proposal will fill this void through a collaborative effort combining biophysical experiments and computational methods.

PI_NAMEs: LORIA, JOSEPH P (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Active Sites;Allosteric Regulation;Allosteric Site;Amino Acids;amino group;Architecture;Aspartic Acid;Binding;Binding Proteins;Binding Sites;Biochemical;Biochemistry;Biological;Biological Assay;Biological Process;biophysical analysis;Biophysics;Catalysis;Cells;Cellular biology;Chemicals;computer studies;Computing Methodologies;Disease;Distal;Distant;Drug Targeting;Enzymes;Epidermal Growth Factor Receptor;ERBB2 gene;Excision;Exhibits;experimental study;extracellular;Family member;Funding;Goals;H1-related protein-tyrosine phosphatase;Health;Human;human disease;Immune System Diseases;improved;In Vitro;in vivo;Inflammation;inhibitor;inorganic phosphate;insight;Insulin Receptor;JAK2 gene;Kinetics;Ligand Binding;Ligands;Link;Malignant Neoplasms;MAPK1 gene;MAPK3 gene;MAPK8 gene;Medical;Methods;Molecular;molecular dynamics;Monitor;Motion;Mutate;Mutation;NMR Spectroscopy;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear Magnetic Resonance;Obesity;Paint;Pathway Analysis;Peptides;Pharmaceutical Preparations;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Physiological;Play;Productivity;Protein Dephosphorylation;Protein Family;protein function;protein structure;Protein Tyrosine Phosphatase;protein tyrosine phosphatase 1B;Proteins;Research;Role;screening;Signaling Protein;Site;small molecule;Specificity;Stat5 protein;Structure;Substrate Specificity;success;Sumoylation Pathway;Testing;Therapeutic;Thermodynamics;Tyrosine;Vaccinia;Validation

PROJECT_TITLE: Investigating the relationship between allostery and substrate specificity in protein tyrosine phosphatases

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Data Science;Genetics;Human Genome;Lung;Lung Cancer;Precision Medicine;Prevention

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE  We propose to conduct a well-powered transcriptome-wide association study and methylation-wide association study to discover novel genes and methylation markers for lung cancer risk. We will also evaluate the differences in the expression levels of TWAS-identified genes and the methylation levels of MeWAS- identified loci between lung cancer tissues and normal tissues, investigate the regulating effects of methylation sites on the expression of promising genes by functional genomics analyses, and perform functional analyses to evaluate the potential functions of identified genes and methylation loci. Our results will help us to better understand the mechanistic relationship between genetic and epigenetic variations and how those variations relate to lung cancer risk and may lead to the discovery of biomarkers that would facilitate early detection of lung cancer and the development of targeted gene therapies for personalized treatment.

PI_NAMEs: CAI, QIUYIN  (contact);LONG, JIRONG

PROGRAM_OFFICER_NAME: CARRICK, DANIELLE M

PROJECT_TERMS: Attenuated;biobank;Biological;Biological Assay;biomarker discovery;Cancer Biology;Cancer Etiology;cancer genetics;Cancer Patient;cancer risk;causal variant;Cessation of life;Chest;cost;cost efficient;Country;CRISPR/Cas technology;Data;Data Set;density;Development;Disease susceptibility;disorder prevention;disorder risk;DNA Methylation;epigenetic variation;functional genomics;Gene Expression;gene function;gene-targeted therapy;Genes;Genetic;Genetic Diseases;Genetic Markers;Genetic Models;genetic variant;Genetic Variation;genome wide association study;genomic data;genomic locus;Genomics;Genotype;Genotype-Tissue Expression Project;Immune response;improved;In Vitro;in vitro Assay;innovation;instrument;IRF4 gene;lung cancer screening;lung carcinogenesis;Lung Neoplasms;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of ovary;Malignant neoplasm of prostate;Methodology;Methylation;methylation biomarker;methylome;methylomics;Modeling;Multiomic Data;Normal tissue morphology;novel;novel strategies;Patients;personalized medicine;Phenotype;Pilot Projects;Play;predictive modeling;Prevention;programs;Reporting;Risk;risk variant;Role;Sample Size;Series;Site;Structure of parenchyma of lung;Susceptibility Gene;System;The Cancer Genome Atlas;Tissue Sample;Tissues;transcriptome;transcriptome sequencing;transcriptomics;Translating;translational genetics;tumor;Tumor Tissue;United States;Variant

PROJECT_TITLE: Identification of Genes and DNA Methylation Markers for Lung Cancer Risk by Integrating Multi-omics Data

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Charcot-Marie-Tooth Disease;Clinical Research;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Rare Diseases

ORG_CITY: HOUSTON

ORG_DEPT: GENETICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: The project will provide new insights into mechanisms underlying complex genomic changes resulting from DNA rearrangements - a common cause of neurological disease. This will enable better diagnostics and potential new avenues for therapy by the correction of gene dosage further supporting the Precision Medicine Initiative. Such genomic rearrangements cause gene copy number variations resulting in neurodevelopmental disorders including intellectual disability, behavioral disorders such as autism, psychiatric conditions such as schizophrenia, and neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Charcot-Marie-Tooth disorders.

PI_NAMEs: LUPSKI, JAMES R. (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Adult;Alzheimer's Disease;autism spectrum disorder;Automobile Driving;Behavior Disorders;Biological Assay;Characteristics;Charcot-Marie-Tooth Disease;Chromosomal Rearrangement;chromothripsis;comparative genomic hybridization;Complex;Copy Number Polymorphism;Diagnostic;Disease;DNA Sequence Rearrangement;Evaluation;Evolution;exome sequencing;gene correction;Gene Dosage;Gene Rearrangement;Genes;Genetic;Genome;genome sequencing;genome-wide;Genomic approach;Genomic Instability;Genomic Segment;Genomics;Heterozygote;Human;Individual;insight;Intellectual functioning disability;malformation;Malignant Neoplasms;Maps;Molecular;Mutation;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;Neurodevelopmental Disorder;novel;Parkinson Disease;Pattern;Potocki-Lupski syndrome;Precision Medicine Initiative;Process;Recurrence;Role;Schizophrenia;SNP array;Stretching;trait;Variant;whole genome

PROJECT_TITLE: STRUCTURAL VARIATION IN NEUROLOGICAL DISEASE


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Childhood Injury;Clinical Research;Diabetes;Pediatric;Prevention

ORG_CITY: LEXINGTON

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Project Narrative Individuals with Type 1 diabetes have higher fracture rates and smaller and weaker muscles compared to those without diabetes, even in young ages. With this project we will try to identify whether a molecule that comes from skeletal muscle, called myostatin, is involved in the increased risk of fractures and the poor quality of skeletal muscle in young individuals with Type 1 diabetes.

PI_NAMEs: KALAITZOGLOU, EVANGELIA  (contact)

PROGRAM_OFFICER_NAME: MALOZOWSKI, SAUL N

PROJECT_TERMS: 20 year old;Activin Receptor;Address;Affect;Age;Animal Model;Antibodies;Basic Science;Biopsy;bone;bone cell;Bone Density;bone fracture repair;bone imaging;Bone Marrow Stem Cell;bone mass;Bone Resorption;bone turnover;career;career development;Cell Line;Cells;Childhood;Clinical;Clinical Research;clinically significant;Communication;Complication;Complications of Diabetes Mellitus;cost;Data;Development;Diabetes Mellitus;diabetic;diabetic bone disease;diabetogenic;Disease;Endocrine;Endocrinology;Environment;Equipment;Exhibits;Foundations;Fracture;fracture risk;FRAP1 gene;Functional disorder;Future;GDF8 gene;Gene Expression;Gene Proteins;General Population;Genes;Health;high risk;Hip Fractures;Hip region structure;Human;Hyperglycemia;Impairment;improved;In Vitro;in vivo;Incidence;Incidental Findings;Individual;Insulin deficiency;Insulin-Dependent Diabetes Mellitus;Intervention;Kentucky;Knowledge;Laboratories;Life;MAP Kinase Gene;Measures;Mechanics;Mediating;Mediator;Mentors;mineralization;mouse model;Mus;Muscle;muscle form;Muscle function;Musculoskeletal;Musculoskeletal Diseases;Musculoskeletal System;novel;Nurses' Health Study;osteoblast differentiation;Osteoblasts;Osteocalcin;Osteocytes;Osteogenesis;Outcome;paracrine;Pathway interactions;Pediatrics;pharmacologic;Phenotype;Physical Capacity;Population;Population Study;Positioning Attribute;Prevalence;prevent;Prevention;professor;Program Development;prospective;receptor;reduced muscle mass;reduced muscle strength;Relative Risks;Research;Resources;Risk;Roentgen Rays;Role;Sampling;Scientist;Serum;Signal Pathway;Signal Transduction;Skeletal bone;Skeletal Muscle;skills;Time;Trabecular Bone Score;Translational Research;Universities;Upper Extremity Fracture;Work;young adult

PROJECT_TITLE: Muscle bone interaction and its role in diabetic bone disease of Type I diabetes

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: BOSTON

ORG_DEPT: BIOLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: Project Narrative Our study will provide new insights into the control and manipulation of the p53 pathway, one of the most important pathway protecting human cells against the development of cancer. Specifically, it will give a quantitative understanding of how p53 is controlled in individual cells; how it turns appropriate genes on and off, how this control is misregulated in cancers; and how therapeutic strategies to manipulate p53 activity can be combined with other cancer treatments to eliminate tumor cells. The knowledge gained from these studies will advance our understanding of how p53 operates in normal and cancer cells and help translate our insights to address important clinical needs.

PI_NAMEs: LAHAV, GALIT  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: 3-Dimensional;Address;Affect;Architecture;cancer cell;cancer therapy;Cell Death;Cell Fate Control;cell killing;Cells;Cellular Stress;Clinical;clinically relevant;combinatorial;Data;Development;DNA Damage;Dose;Environment;Gene Expression;Genes;Goals;Human;Image;imaging system;Immune;Immune system;Immunotherapy;in vivo;Individual;inhibitor;insight;Knowledge;Link;Malignant Neoplasms;Mediating;mutant;neoplastic cell;new technology;Normal Cell;novel;Outcome;overexpression;Pathway interactions;Pattern;Population;Post-Translational Protein Processing;Predisposition;Process;programs;protective pathway;Proteins;Radiation;Regulation;response;RNA;Schedule;Signal Transduction;single-cell RNA sequencing;spheroids;Stimulus;System;targeted treatment;Therapeutic;Time;TP53 gene;transcription factor;Translating;tumor;Tumor Suppressor Proteins;Work

PROJECT_TITLE: Dynamics, Regulation and Function of p53 in Single Cells

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


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Breastfeeding, Lactation and Breast Milk;Clinical Research;Clinical Trials and Supportive Activities;Cost Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infant Mortality;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: CHICAGO

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

ORG_STATE: IL

PHR: Project Narrative Black very low birth weight infants are significantly less likely to receive mother’s own milk. The costs associated with adhering to pumping are borne by mothers and contribute to this disparity. This randomized controlled trial will test an intervention to offset costs associated with pumping and its cost effectiveness.

PI_NAMEs: JOHNSON, TRICIA J.;PATEL, ALOKA LAHOTI (contact)

PROGRAM_OFFICER_NAME: DAGHER, RADA K

PROJECT_TERMS: Address;Adherence;Adopted;Adoption;Affect;African American;Asian;authority;Behavior;Benchmarking;Birth;Birth Weight;Black race;breast pump;Bronchopulmonary Dysplasia;Child;comparative cost effectiveness;coping;cost;Cost Analysis;cost comparison;cost effectiveness;Cost Effectiveness Analysis;Data;Deposition;Disparity;disparity reduction;Donor Exclusions;Dose;economic evaluation;Economics;effectiveness evaluation;Effectiveness of Interventions;emotional distress;Employee;Equipment;Family;feeding;Funding;Goals;Health;Hispanic;Home;hospital readmission;Hospitalization;Hospitals;Hour;Household Heads;Human Milk;improved;Infant;infant outcome;Inferior;Infrastructure;innovation;International;Intervention;Lactation;late onset sepsis;Life;Low income;Maternal Behavior;maternal outcome;Measures;Mediating;Milk;milk volume;Morbidity - disease rate;Mothers;Native Americans;Necrotizing Enterocolitis;Neonatal Intensive Care Units;Neurodevelopmental Problem;Not Hispanic or Latino;novel;opportunity cost;Outcome;pasteurization;payment;Population;Poverty;Predisposition;primary outcome;Pump;Quality Indicator;randomized, clinical trials;Randomized, Controlled Trials;Recommendation;Regimen;Research;response;Risk;Risk Reduction;secondary outcome;Sepsis;standard of care;Testing;Training;Transportation;United States National Institutes of Health;Very Low Birth Weight Infant;Work

PROJECT_TITLE: Reducing Disparity in Receipt of Mother’s Own Milk in Very Low Birth Weight Infants: An Economic Intervention to Improve Adherence to Sustained Maternal Breast Pump Use

STUDY_SECTION: HDEP

STUDY_SECTION_NAME: Health Disparities and Equity Promotion Study Section[HDEP]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Pediatric;Prevention

ORG_CITY: Charlestown

ORG_NAME: MGH INSTITUTE OF HEALTH PROFESSIONS

PHR: PROJECT NARRATIVE This Randomized Controlled Trial (RCT) aims to translate years of basic research into clinical practice by providing early evidence-based language and comprehension intervention to those most vulnerable for reading comprehension failure. This project is relevant to the NIDCD's mission to improve the lives of individuals with communication disorders because findings from the proposed studies are expected to be informative for refinement of prognosis and treatment methods for this population, which includes children with low language comprehension, many of whom have Developmental Language Disorder (DLD). This project is also relevant to the broader field of public health because of the importance of language and literacy skills to quality of life outcomes.

PI_NAMEs: HOGAN, TIFFANY P (contact);PIASTA, SHAYNE B.

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Age;Area;base;Basic Science;Child;Child Language;Clinical;clinical practice;Clinical Trials;Communication impairment;Complex;Comprehension;comprehension skill;Developmental Process;dosage;Education;Educational Curriculum;Educational process of instructing;efficacy evaluation;efficacy testing;efficacy trial;elementary school;evidence base;Evidence based practice;Failure;Family;Foundations;Funding;Goals;Grant;Guidelines;Head;Human;implementation intervention;improved;Individual;innovation;Instruction;Intervention;intervention effect;Language;language comprehension;Language Development Disorders;listening comprehension;literacy;Methods;Mission;multidisciplinary;National Institute on Deafness and Other Communication Disorders;non-verbal;Oral;Outcome;Phase;Population;Prevention;Printing;Process;Prognosis;Public Health;Quality of life;Randomized, Controlled Trials;Reading;reading comprehension;Research;Research Activity;Research Personnel;research to practice;Risk;Schools;Science;Site;skills;Socioeconomic Status;System;Translating

PROJECT_TITLE: Translating research into school-based practice via small-group, language-focused comprehension intervention


ADMINISTERING_IC: EY

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE The integration of color and form is an enriching and often necessary component of visual perception. Thus, deficits and abnormalities in visual feature integration, common to many ophthalmologic and neuropsychiatric disorders, are debilitating to those afflicted. This proposal will expand our fundamental understanding of how the brain processes color and integrates it into visual space, paving the way to possible therapies for visual processing deficits.

PI_NAMEs: SANTIAGO MORENO, JUAN GABRIEL (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Architecture;area striata;Behavior;Biophysics;Brain;career;Cell Shape;Cells;Clinical;Color;color processing;Complex;Comprehension;computational neuroscience;Computer Models;Computing Methodologies;Contrast Sensitivity;Data;Data Analyses;density;Electrophysiology (science);Environment;experience;experimental study;Form Perception;Future;Goals;Impairment;information processing;insight;Knowledge;large scale data;Lateral Geniculate Body;Lighting;luminance;Mammals;Measures;Methods;model organism;Motion;Mus;neural;neural information processing;neuromechanism;Neurons;neuropsychiatric disorder;novel;Pathology;Patients;Photoreceptors;Physicians;Population;preference;Process;Property;Resolution;response;Retina;Retinal Photoreceptors;Scientist;Signal Transduction;spatial integration;spatiotemporal;Specificity;Stimulus;Stream;Structure;Support System;Synapses;System;Testing;Thalamic structure;Therapeutic;Training;Translating;V1 neuron;Variant;Visual;Visual Motion;Visual Perception;visual processing;Visual System;Work

PROJECT_TITLE: Thalamocortical mechanisms producing spatial chromatic contrast in mouse V1


ORG_CITY: PHILADELPHIA

ORG_DEPT: NEUROSCIENCES

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE Fast and efficient neurotransmission is essential for normal brain function, and a thorough understanding of how synapses are organized is essential to our understanding of neurological diseases. The pre-synaptic calcium sensor Synaptotagmin VII (SYT7) has been recently linked to Bipolar Disorder, ALS and numerous cancers, yet its localization in neurons remains debated. Here, we will answer key outstanding questions surrounding SYT7 by determining its cellular and nanoscale localization at synapses.

PI_NAMEs: CAIN, RACHEL  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Agreement;Apoptosis;Applications Grants;Architecture;Award;Biochemical;Biochemistry;Biological Assay;Biotinylation;Bipolar Disorder;Brain;Calcium;Cell membrane;Cell surface;Cell Surface Proteins;Central Nervous System;channel blockers;Color;Data;design;Disease;DLG4 gene;Docking;experimental study;Family member;Fellowship;Functional disorder;Head and Neck Cancer;Image;inhibitor;insight;Learning;Link;Malignant neoplasm of brain;Malignant Neoplasms;Membrane Proteins;Mental disorders;Mus;nanocolumn;nanoscale;Nervous System Disorder;Neurons;neurotransmission;neurotransmitter release;NMDA receptor A1;Oncogenes;overexpression;Physicians;postsynaptic;Preparation;presynaptic;Presynaptic Terminals;Prostate;Protein Family;protein function;Proteins;Publishing;Rattus;Recycling;Role;Scientist;sensor;Site;skills;Slice;Stains;Structural Models;Structure;superresolution microscopy;Surface;Synapses;Synaptic Cleft;Synaptic Transmission;synaptotagmin;synaptotagmin VII;Testing;Tetrodotoxin;Training;transmission process;Tretinoin;ultra high resolution;Vertebral column;Vesicle;vesicular release;Work

PROJECT_TITLE: Determining the cellular and nanoscale localization of Synaptotagmin VII


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Digestive Diseases;Liver Cancer;Liver Disease;Machine Learning and Artificial Intelligence;Radiation Oncology;Rare Diseases

ORG_CITY: MADISON

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Histotripsy is a noninvasive, nonthermal and nonionizing ablation modality that has recently undergone a successful phase I human clinical trial. However, a critical limitation to more widespread adoption is the reliance on fixed 2D ultrasound for targeting the tumor, monitoring the ablation, and assessing the ablation zone. In this grant, we will develop a C-arm based platform to accurately and automatically target liver tissue for histotripsy as well as validate prospectively in real-time the performance of the platform in in vivo large animal (porcine, rabbit VX2) models.

PI_NAMEs: LAESEKE, PAUL F (contact);WAGNER, MARTIN GERD

PROGRAM_OFFICER_NAME: LIU, GUOYING

PROJECT_TERMS: 3-Dimensional;Ablation;Adoption;Alcoholism;Algorithms;Animals;anti-cancer;arm;Biological;bone;Breathing;Cancer Etiology;Cessation of life;checkpoint inhibition;Clinical;clinical translation;Clinical Trials;Compensation;Complement;cone-beam computed tomography;Data;deep learning;Dependence;design;Development;Disease;Effectiveness;Environment;expiration;Failure;Family suidae;Fluoroscopy;Focused Ultrasound Therapy;Gases;Goals;Grant;Hepatic;Hepatitis B;Hepatitis C;Human;Image;image guided;imaging capabilities;imaging modality;imaging platform;imaging system;Immune;improved;in vivo;Institution;Intestines;Kidney;Liver;Liver neoplasms;Location;Lung;Magnetic Resonance Imaging;Measures;Methods;Microbubbles;Modality;Modeling;Monitor;Morphologic artifacts;Motion;multidisciplinary;non-alcoholic fatty liver disease;novel;Oryctolagus cuniculus;Pancreas;Patients;Penetration;Performance;Phase;Phase I Clinical Trials;physical process;Physiologic pulse;porcine model;Positioning Attribute;Primary carcinoma of the liver cells;Primary Malignant Neoplasm of Liver;prospective;Radiation therapy;Respiration;respiratory;Respiratory Diaphragm;Robotics;Rodent;Roentgen Rays;Safety;Shapes;simulation;sound;Speed;standard of care;System;targeted imaging;Techniques;Testing;Therapeutic;Thermal Ablation Therapy;Time;Tissues;training data;Transducers;treatment planning;tumor;Ultrasonic Therapy;Ultrasonography;ultrasound;validation studies;Visualization;Work;X-Ray Computed Tomography

PROJECT_TITLE: Advanced C-arm imaging platform for histotripsy treatment of liver tumors

STUDY_SECTION: IGIS

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

PHR: Project Narrative Social memory is essential for the human experience – remembering others enables us to form relationships and successfully navigate through society. The social memory deficits common to many neuropsychiatric disorders are thus debilitating. This proposal will expand our fundamental understanding of how the brain forms and recalls lasting social memories, paving the way to possible therapies for social memory deficits.

PI_NAMEs: SHEERAN, WILLIAM M (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: Alzheimer's Disease;Area;Base Pairing;Brain;Brain region;career;cellular imaging;clinical translation;Cognitive Therapy;Communication;comparative;daily functioning;Data;Disease;Dissection;Distant;Elements;Emotional;Ensure;experience;Family;Friends;frontal lobe;Future;Genetic;Goals;Hippocampus;Human;Impaired cognition;Impairment;in vivo calcium imaging;Knowledge;Label;Laboratories;long term memory;Longitudinal Studies;Maintenance;Medial;member;Memory;memory acquisition;memory consolidation;memory encoding;Memory impairment;memory process;memory recall;memory recognition;Methods;Microtus;Modeling;mouse model;Mus;Nature;neural;neural circuit;neuromechanism;Neurons;neuropsychiatric disorder;neuropsychiatry;Neurosciences;neurotechnology;neurotransmission;novel;Pair Bond;Partner in relationship;Pathway interactions;Persons;Physicians;Population;Post-Traumatic Stress Disorders;prairie vole;preference;Prefrontal Cortex;prevent;Process;Proxy;psychological distress;Rattus;recruit;Rodent;Rodent Model;Role;Signal Transduction;social;Social Interaction;Societies;System;Technology;Testing;therapeutically effective;Time;Training;Translating;Translations;Work

PROJECT_TITLE: Investigating the role of hippocampocortical circuitry in long term social memory.


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Lymphatic Research;Lymphedema;Prevention;Women's Health Research

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative Breast cancer related lymphedema affects 1.2 million patients in the U.S. and is one of the most significant cancer survivorship burdens. Our proposal aims to identify normal variations in lymphatic anatomy and function that predispose women to lymphedema.

PI_NAMEs: SINGHAL, DHRUV  (contact)

PROGRAM_OFFICER_NAME: GALIS, ZORINA S

PROJECT_TERMS: Affect;Anatomy;Area;arm;arm function;Attention;Axilla;Axillary Lymph Node Dissection;Axillary lymph node group;Back;Bilateral;Breast Cancer Patient;Breast Cancer survivor;Breast Cancer Treatment;Cadaver;Cancer Survivorship;Circulation;Clinical;cost;Data;Development;Disease;Dissection;Dyes;Event;Fatigue;Female;fluorophore;Goals;Hand;high risk;High-Risk Cancer;Imaging Techniques;individual variation;Indocyanine Green;Infection;Injury;innovation;intraoperative optical imaging;Life;Lymph;Lymphatic;lymphatic drainage;Lymphatic function;Lymphatic System;Lymphedema;Lymphography;lymphoscintigraphy;Malignant Breast Neoplasm;Malignant Female Reproductive System Neoplasm;Malignant Neoplasms;Maps;Measures;Medical Care Costs;Methods;Modeling;Modernization;novel;nuclear imaging;Operating Rooms;operation;Operative Surgical Procedures;Pain;Pathway interactions;Patient risk;Patients;Physical therapy;Population;Positive Lymph Node;prevent;Prevention;preventive intervention;Procedures;Prospective Studies;Quality of life;Radiation;Risk;Risk Factors;Sarcoma;Scanning;Secondary to;Skin Cancer;standard care;Symptoms;temporal measurement;Testing;Time;Tissues;treatment strategy;United States;Upper arm;Upper Extremity;Urologic Cancer;Variant;volunteer;Woman

PROJECT_TITLE: Mapping & quantifying lymphatic drainage of the arm's alternate pathway


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Epilepsy;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Precision Medicine

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Cardiac arrest impacts the lives of 500,000 Americans every year, and nearly half of patients surviving the initial resuscitation will develop seizures or seizure-like brain activity as a complication of hypoxic-ischemic brain injury. We aim to reduce secondary brain injury and neurological disability from seizures after cardiac arrest by personalizing seizure treatment using EEG and brain MRI biomarkers of neuro-recovery. We expect that the outcome of the proposed studies will provide critical knowledge about epileptogenesis after hypoxic-ischemic brain injury andguide the development of goal-directed seizure treatment and patient selection in future clinical trials.

PI_NAMEs: AMORIM, EDILBERTO  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Acceleration;Acute;Acute Brain Injuries;American;Anesthetics;Anticonvulsants;Area;authority;Big Data Methods;Biological Markers;biomarker driven;Biomedical Technology;Biometry;Brain;Brain imaging;Brain Injuries;brain magnetic resonance imaging;California;career development;Caring;Categories;Cause of Death;Cerebrum;Clinical;Clinical Trials;Clinical Trials Design;cohort;Collaborations;Coma;Complication;Computing Methodologies;Critical Care;Data;Data Scientist;Data Set;Decision Making;deep learning;deep learning algorithm;Development;Development Plans;Diagnosis;Diffusion Magnetic Resonance Imaging;Early identification;Educational Curriculum;Electroencephalography;Environment;Epilepsy;epileptiform;Epileptogenesis;Evolution;Feedback;Frequencies;Future;Goals;hands-on learning;Heart Arrest;Hospitals;Hour;Human;Hypoxic-Ischemic Brain Injury;improved;improved outcome;Individual;Infusion procedures;Injury;innovation;insight;International;Intervention Trial;K-Series Research Career Programs;Knowledge;Machine Learning;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Mediating;Mentors;Methods;Modeling;Monitor;Morphology;MRI Scans;multidisciplinary;natural hypothermia;Nervous System Disorder;neuroimaging;Neurological disability;Neurological outcome;neurological recovery;Neurologist;neurophysiology;Outcome;outcome prediction;Patient Selection;Patients;Performance;personalized medicine;Phenotype;Physiology;Positioning Attribute;Prediction of Response to Therapy;predictive marker;prevent;prognostication;programs;Propofol;Publishing;Recovery;Recovery of Function;Recurrence;Refractory;Research;Research Personnel;resilience biomarker;response biomarker;Resuscitation;San Francisco;Scientist;Seizures;Selection for Treatments;Series;skills;Specificity;Survivors;Techniques;technological innovation;Testing;Therapeutic;Therapeutic Intervention;Time;Titrations;Training;treatment effect;treatment response;treatment strategy;trend;Universities;Validation;Weaning;Work

PROJECT_TITLE: Physiology-driven seizure management post-cardiac arrest

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Genetics

ORG_CITY: Los Angeles

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Our proposal describes multiple approaches to uncover the mechanisms underlying H3 tail proteolysis- mediated gene activation during osteoclast differentiation. The results from this study will provide opportunities for developing therapeutics to treat a large number of devastating bone diseases.

PI_NAMEs: AN, WOOJIN  (contact)

PROGRAM_OFFICER_NAME: CHEN, FAYE H

PROJECT_TERMS: Acetylation;Binding;Biochemical;Biological Assay;Biological Process;Bone Development;Bone Diseases;Bone Regeneration;Bone remodeling;Bone Resorption;Catalytic Domain;Cell Differentiation process;Cell Nucleus;Cells;Chromatin;Chromatin Structure;Chromatin Structure Alteration;Clustered Regularly Interspaced Short Palindromic Repeats;collaborative environment;CRISPR/Cas technology;crosslink;Data;Deoxyribonuclease I;Digestion;Disulfides;DNA;domain mapping;EP300 gene;Epigenetic Process;epigenetic regulation;epigenome;Event;Excision;experimental study;Extracellular Matrix;Family;Gelatinase B;Gene Abnormality;Gene Activation;Gene Expression;Gene Silencing;Genes;Genetic Transcription;genome-wide;Goals;Guide RNA;hematopoietic differentiation;Histone H3;Histones;Hydroxyl Radical;In Vitro;in vivo;insight;Laboratories;Light;Link;Macrophage;Maintenance;Maps;Matrix Metalloproteinases;Mediating;Mediator;member;Methylation;Modeling;Molecular;Molecular Conformation;monocyte;Mononuclear;N-terminal;Nucleosomes;osteoclastogenesis;Osteoclasts;Pathway interactions;Peptide Hydrolases;Peptides;Permeability;Play;precursor cell;Process;programs;Property;Proteolysis;reconstitution;recruit;Regulatory Pathway;Research;Role;Secure;Series;Signal Pathway;Signal Transduction;Site;skeletal;skeletal disorder;System;Tail;Techniques;Therapeutic;TNFSF11 gene;tool;Transactivation;Transcription Repressor;Transcriptional Activation;Transcriptional Regulation;transcriptome sequencing;Work

PROJECT_TITLE: Epigenetic Regulation of Osteoclastogenic Gene Expression: Factors, Targets, and Mechanisms

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Patient Safety

ORG_CITY: DAVIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Phase 1 trials are a critical first step in the search for new treatments and cures for serious neurological diseases. In order to conduct these studies ethically, research ethics committees must determine both that the risks of the trials are reasonable in relation to their potential benefits and that research candidates are given the key information they need in order to understand the potential risks and benefits in such a trial. These committees currently are not provided with instructions from the Department of Health and Human Services for determining whether there is a reasonable ratio between risks and benefits or what counts as the key information about them that need to be disclosed to research candidates. This project will develop and test new strategies and materials that can assist research ethics committees to make these critical determinations.

PI_NAMEs: FEDYK, MARK  (contact);KIMMELMAN, JONATHAN M

PROGRAM_OFFICER_NAME: HARTMAN, ADAM L

PROJECT_TERMS: Authorization documentation;Benefits and Risks;Brain;Characteristics;Clinical;clinical efficacy;Clinical Research;clinical translation;common rule;Computer software;CRISPR/Cas technology;Data;Data Analytics;Decision Aid;Decision Making;design;Disclosure;Disease;early phase trial;effective therapy;efficacy study;Enrollment;Ethics;falls;Future;Health;Human;improved;Informed Consent;Institutional Review Boards;Instruction;International;Interview;Investigational Drugs;Judgment;Learning;Legal;Life;member;Modality;Modeling;Morals;Nervous System Disorder;novel;Occupations;Online Systems;Organoids;Participant;Persons;Phase;phase 1 study;phase I trial;pilot test;pre-clinical;preclinical efficacy;preclinical safety;preclinical study;Process;Qualitative Research;Research;Research Ethics Committees;Research Personnel;Research Technics;Resources;Risk;Safety;safety testing;Specificity;Structure;Surveys;Technology;Testing;Text;therapeutic development;tool;Translations;Uncertainty;United States Dept. of Health and Human Services;United States Food and Drug Administration

PROJECT_TITLE: The RATIOS Study: Risk/benefit AssessmenT by IRB review of Phase One Studies


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative Lung cancer is the leading cause of cancer related deaths worldwide and many patients eventually stop responding to treatments including immunotherapies, so a better understanding of why patients stop responding will help us develop strategies to overcome this challenge. My current work uses novel mouse models of lung cancer to investigate mechanisms of acquired resistance to immune checkpoint inhibitors, whereas my postdoctoral work will focus on developing efficacious neoantigen vaccines that induce tissue resident memory T cells. In both settings, my overarching goal is to produce strategies to expand immunotherapy benefits to a broader patient population.

PI_NAMEs: ROBLES-OTEIZA, CAMILA  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Address;Advanced Development;anti-PD-1;Antigen Presentation;Antigen Presentation Pathway;Antitumor Response;Automobile Driving;Biological Models;Biopsy;Cancer Etiology;Cancer Patient;cancer therapy;cancer type;Cancer Vaccines;candidate validation;Carcinogens;Categories;CD8B1 gene;Cell Physiology;Cessation of life;checkpoint inhibition;checkpoint therapy;chemotherapy;Clinical;Clinical Research;Correlation Studies;Defect;Disease;Disseminated Malignant Neoplasm;DNA Replication Proofreading;Enzymes;exome sequencing;experimental study;Genes;Genetic;Genetic Transcription;Genetically Engineered Mouse;Goals;Harvest;Human;human disease;Immune;Immune checkpoint inhibitor;Immune response;Immunotherapy;improved;in vivo;innovation;insight;K-ras mouse model;Lung Adenocarcinoma;Malignant neoplasm of lung;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Methods;MHC Class I Genes;Minority;Modeling;mouse model;Mus;mutant;Mutation;neoantigen vaccine;neoantigens;neoplastic cell;Non-Small-Cell Lung Carcinoma;nonsynonymous mutation;novel;Oncogenic;patient derived xenograft model;patient population;Patients;Peripheral;personalized therapeutic;Phase;Positioning Attribute;Postdoctoral Fellow;pre-clinical;programmed cell death protein 1;programs;Research;Resistance;resistance mechanism;response;Signal Transduction;single-cell RNA sequencing;Site;standard of care;Survival Rate;T cell infiltration;T cell response;T memory cell;T-Lymphocyte;T-Lymphocyte Subsets;targeted treatment;Testing;therapeutic vaccine;tissue resident memory T cell;Tissues;tool;tumor;tumor growth;Tumor Immunity;tumor microenvironment;vaccine development;Vaccines;Work

PROJECT_TITLE: Investigating Immune Responses to Neoantigen Cancer Vaccines using In Vivo Functionalized Lineage


NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Hematology;Infectious Diseases;Sepsis

ORG_CITY: LOS ANGELES

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

PHR: Project Narrative Numerous intestinal diseases, including necrotizing enterocolitis and inflammatory bowel dis- ease, have disruption of the intestinal barrier. Absence of the bile acid receptor FXR protects animals from acute intestinal injury by maintaining their intestinal barrier. Because FXR may be responsible for gut barrier failure in acute injury, this research proposal will explore the signaling cascades involved in these effects with relevance to human disease.

PI_NAMEs: GAYER, CHRISTOPHER  (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Acids;Acute;Affect;Agonist;Animals;Apical;Award;bile acid transporter;Bile Acids;Body System;Bone Marrow;career development;cecal ligation puncture;Cells;Cessation of life;Chronic;Colon;cytokine;Data;Defect;Development;Dichloromethylene Diphosphonate;Disease;disease model;Disease Progression;Dominant Negative Receptor;Epidermal Growth Factor Receptor;Epithelial Cells;Epithelium;Experimental Designs;experimental study;Failure;farnesoid X-activated receptor;fluorescein isothiocyanate dextran;gastrointestinal;Genetically Modified Animals;Goals;Growth Factor;Growth Factor Receptors;gut inflammation;human disease;Immune;Impairment;improved;improved outcome;In Vitro;in vivo;in vivo evaluation;in vivo Model;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Injections;Injury;insight;intestinal barrier;Intestinal Diseases;intestinal epithelium;intestinal injury;Intestines;Knock-out;knockout animal;Knockout Mice;Link;Liposomes;Macrophage;Measures;Mediating;Mentors;Modeling;monolayer;Mucous Membrane;Mus;Necrotizing Enterocolitis;occludin;Organ failure;Organoids;Outcome;Outcome Study;Pathology;Pathway interactions;Patient-Focused Outcomes;Permeability;pharmacologic;physiologic model;Physiology;prevent;protein activation;protein expression;Proteins;Publications;receptor;Receptor Activation;Receptor Inhibition;Receptor Signaling;Regulation;Reporting;Repression;Research;Research Personnel;Research Project Grants;Research Proposals;response;Role;Scientist;Sepsis;Signal Transduction;Sodium;Source;src-Family Kinases;Surgeon;Testing;Therapeutic;therapeutic target;Thinking;Tight Junctions;Time;Tissues;TNF gene;uptake;Western Blotting

PROJECT_TITLE: The Role of FXR on the Intestinal Barrier in Acute Injury.

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Human Genome;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: ALS and other neurodegenerative diseases are devastating for individuals and families involved; there are no cures and few treatments. Our studies have revealed new insights into ALS contributors TDP-43 and FUS/TLS, defined a new genetic risk factor for ALS – mutations in the ataxin 2 gene and discovered a cellular process to explain how mutations in the C9orf72 gene, the most common known cause of ALS, might contribute to neurodegeneration. The studies proposed will reveal insight into the role of dipeptide repeat proteins abnormally produced from the C9orf72 mutation and will pursue ataxin 2 as a therapeutic target in ALS, laying the foundation for the development of novel therapeutic approaches.

PI_NAMEs: GITLER, AARON D. (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: alpha synuclein;Antisense Oligonucleotides;Award;Biological;c9FTD/ALS;C9ORF72;Cell model;Cell Physiology;Cells;CRISPR screen;CRISPR-mediated transcriptional activation;design;Development;Dipeptides;Disease;experimental study;Family;flexibility;Foundations;Funding;Gene Silencing;Genes;Genetic;genetic approach;genetic risk factor;genome-wide;Human;Human Genetics;Individual;inhibitor;innovation;insight;interest;Laboratories;lariat debranching enzyme;Length;Libraries;life span;Modeling;Molecular;mouse model;Mus;Mutation;National Institute of Neurological Disorders and Stroke;Nerve Degeneration;Neurodegenerative Disorders;Neurons;novel;novel therapeutic intervention;novel therapeutics;Nucleotides;Parkinson Disease;Pathway interactions;polyglutamine;Process;programs;protein TDP-43;Proteins;Research;RNA;Role;SCA2 protein;stem;Testing;therapeutic target;Time;Transgenic Mice;Translating;Translations;Work;yeast genetics;Yeast Model System

PROJECT_TITLE: Innovating Yeast and Human Genetics Approaches to Define Mechanisms of Neurodegenerative Disease


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_DEPT: PHARMACOLOGY

PHR: Project narrative Coronary revascularization (i.e., stent placement) has been adopted worldwide and is the most common modality in patients with coronary heart diseases in the United States. However, it is also among the most costly and is often associated with a high incidence of restenosis (repeat narrowing of a coronary artery). This application aims to elucidate the mechanisms responsible for restenosis and thus identify new therapeutic targets to develop new drugs to treat restenosis after coronary revascularization.

PI_NAMEs: GONG, MING C;GUO, ZHENHENG  (contact)

PROGRAM_OFFICER_NAME: FLEG, JEROME L

PROJECT_TERMS: Abdominal Aortic Aneurysm;Adopted;Affect;Aging;Aldosterone;Alzheimer's Disease;American;Angiotensin II;Arachidonic Acids;ARNTL gene;Arterial Injury;Atherosclerosis;Binding;Biological Assay;Carotid Arteries;Cause of Death;Cell Proliferation;Cells;chromatin immunoprecipitation;circadian pacemaker;Clinical Research;Coronary;Coronary artery;Coronary Artery Bypass;Coronary heart disease;cost;Cytosolic Phospholipase A2;Data;Development;Diabetes Mellitus;Endothelial Cells;Enzymes;Female;femoral artery;Genetic;Genetic Transcription;Goals;Hyperplasia;Hypertension;Immune response;Incidence;Injury;insight;Knockout Mice;Lesion;Ligation;loss of function;male;Malignant Neoplasms;Mediating;men;Messenger RNA;Metabolism;Metals;Modality;Molecular;mouse model;Mus;new therapeutic target;novel therapeutic intervention;novel therapeutics;overexpression;Pathway Analysis;Patients;percutaneous coronary intervention;Personal Satisfaction;Pharmaceutical Preparations;Platelet-Derived Growth Factor;pleiotropism;pre-clinical;Proliferating;promoter;Reporting;restenosis;revascularization;Risk;Role;Scheme;Signal Transduction;Site;Sleep;Smooth Muscle Myocytes;stent thrombosis;Stents;Testing;Thrombosis;Time;transcription factor;transcriptome sequencing;United States;Up-Regulation;vascular inflammation;vascular injury;Vascular remodeling;Vascular Smooth Muscle;Woman

PROJECT_TITLE: Targeting smooth muscle cell BMAL1 as a new therapeutic strategy against restenosis

STUDY_SECTION: IVPP

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


ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: The ability to sense force is critical for myriad functions in the body, yet the molecular mechanisms of force-sensing are the least understood among all sensory systems. We identified the mechanically-activated Piezo2 ion channel, and showed that it plays a critical role in detecting touch, proprioception and lung stretch, but not noxious mechanical stimuli. In this proposal, we describe approaches we will take to explore the roles of Piezo2 in various forms of internal-organ mechanotransduction and to identify the elusive receptors involved in mechanical pain.

PI_NAMEs: PATAPOUTIAN, ARDEM  (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Cations;Functional disorder;functional genomics;Genomic approach;Hearing;high throughput screening;Interoception;Ion Channel;Lung;mechanical force;mechanical stimulus;Mechanics;mechanotransduction;Mediating;Molecular;Nervous System;Organ;Pain;pain perception;Physiological;Physiology;Piezo 1 ion channel;Piezo 2 ion channel;Play;Process;Proprioception;receptor;Role;Satiation;sensor;Sensory;sensory system;Smell Perception;Stretching;System;Taste Perception;therapeutic target;Touch sensation;Vision

PROJECT_TITLE: Mechanisms of force sensing in the nervous system


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Contraception/Reproduction;Endocrine Disruptors;Estrogen;Fibroid Tumors (Uterine);Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Women's Health Research

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Uterine fibroids (leiomyomas) are tumors that affect up to 80% of all women during their lifetime and constitute a major health problem worldwide. MED12 gene mutations occur in approximately 70% of all leiomyomas, and endocrine disruptors are known risk factors; we do not know, however, how these genetic or environmental factors cause tumor growth. We propose to determine the role of the tryptophan-kynurenine-aryl hydrocarbon receptor (AHR) pathway that is activated by these factors in tumorigenesis. We expect that our proposal will lead to a better understanding of this understudied disease and future development of new treatments.

PI_NAMEs: BULUN, SERDAR E. (contact);YIN, PING

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Affect;Age;amino acid metabolism;Amino Acid Transporter;Anemia;antagonist;Apoptosis;ARNT gene;Aryl Hydrocarbon Receptor;aryl hydrocarbon receptor ligand;Bioinformatics;Biological Assay;cell growth;Cell Proliferation;Cell Survival;Cells;Chemical Exposure;Chromatin;consumer product;Development;Diet;Diethylhexyl Phthalate;Disease;Endocrine Disruptors;Environmental Pollutants;Environmental Risk Factor;Enzymes;Epidemiology;epidemiology study;Exposure to;FDA approved;Fibroid Tumor;Future;Gene Expression;Gene Expression Profile;Gene Mutation;Genes;Genetic;genome-wide analysis;Goals;Growth;Health;histone modification;Human;Hysterectomy;In Vitro;in vivo;Inhibition of Apoptosis;inhibitor;knock-down;Kynurenine;Leiomyoma;Ligands;Link;Malignant Neoplasms;Maps;Masks;Mediating;Medical;Metabolism;Molecular;mouse genome;mouse model;mutant;Mutation;myometrium;novel;novel therapeutic intervention;novel therapeutics;Obstruction;Pathogenesis;Pathway interactions;Perimenopause;pharmacologic;phthalates;Pregnancy loss;Premenopause;Process;Production;Progesterone Receptors;Proliferating;Receptor Activation;Recurrence;Reporting;reproductive;reproductive system disorder;research and development;response;Risk Factors;Role;Sampling;small hairpin RNA;Small Interfering RNA;Smooth Muscle Myocytes;steroid hormone;Testing;therapeutic target;Time;Tissues;transcriptome;transcriptome sequencing;Translational Research;Tryptophan;Tryptophan Metabolism Pathway;Tryptophanase;tumor;tumor growth;tumorigenesis;Up-Regulation;uptake;Urine;Uterine Fibroids;Uterine hemorrhage;Uterus;Woman;Xenograft procedure

PROJECT_TITLE: Environmental Pollutants and AHR pathway in Uterine Leiomyoma

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Pain Research;Prescription Drug Misuse;Substance Misuse

ORG_CITY: GAINESVILLE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: NARRATIVE Oxycodone is consistently among medications widely prescribed for pain, but is also widely abused and involved in overdose deaths -- creating an urgent need for interventions that preserve oxycodone analgesia while curtailing its abuse potential. Research shows that syntocinon (the intranasal formulation of the neuropeptide oxytocin) could reduce the abuse liability of opioids, and simultaneously has analgesic properties. The present study will determine if syntocinon will significantly reduce the abuse potential of oxycodone and experimental pain via its effects on brain structure, function and biochemistry, which could lead to a novel therapeutic to curb the opioid crisis.

PI_NAMEs: BERRY, MEREDITH  (contact)

PROGRAM_OFFICER_NAME: LAO, GUIFANG

PROJECT_TERMS: Absence of pain sensation;abuse liability;Acute Pain;addiction;Address;Affect;Analgesics;analog;Animal Model;Animals;antinociception;Area;behavioral economics;behavioral pharmacology;Biochemistry;Brain;brain pathway;Brain region;brain volume;Buprenorphine;Cardiovascular system;career;chronic pain;conditioned place preference;Corpus striatum structure;Dose;Double-Blind Method;Drug Prescriptions;Formulation;Goals;Grant;Health;hedonic;Heroin;Hour;Human;Impairment;Individual;Inflammation;inter-individual variation;Intervention;Intravenous;Laboratory Study;Link;Literature;Manuscripts;Measures;Mechanics;Mediator;Mentors;Methadone;Morbidity - disease rate;Morphine;mortality;Motivation;multidisciplinary;multimodal neuroimaging;multimodality;Mus;neurobiological mechanism;Neurobiology;neuroimaging;Neurons;Neuropeptides;novel;novel therapeutics;Opiate Addiction;Opioid;opioid abuse;opioid epidemic;opioid injection;opioid misuse;opioid mortality;opioid overdose;Opioid replacement therapy;opioid sparing;opioid use disorder;opioid user;Oral;overdose death;Oxycodone;Oxytocin;Pain;pain chronification;Pain Disorder;Pain management;Pain Measurement;pain model;pain reduction;pain sensitivity;Pathway interactions;Percocet;Pharmaceutical Preparations;Pharmacotherapy;Placebo Control;Placebo Effect;Placebos;pre-clinical;Prefrontal Cortex;preservation;prevent;Property;Public Health;Randomized;Rattus;Recreation;Reducing Agents;Regulation;Research;respiratory;response;Rest;Rewards;Scientific Advances and Accomplishments;Self Administration;Sensory;skills;Source;Standardization;Stimulus;Stress;Structure;substance use treatment;Supervision;System;Techniques;Testing;Translations;Writing

PROJECT_TITLE: Opioid-Sparing and Pain-Reducing Properties of Syntocinon:  A Dose-Effect Determination


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Orphan Drug;Rare Diseases

PHR: Project Narrative IL-12 is a powerful cytokine that stimulates both the adaptive and innate immune system to eliminate cancer but safe delivery of therapeutically active doses has been a major barrier to its widespread clinical use. In this application, we will test two unique and potent methods of delivering the IL-12 gene into cancerous tumors in a clinical trial of pet dogs that have naturally developed soft tissue tumors. If successful, this project will both answer fundamental questions regarding the biology of IL-12 and lead to the clinical development of a new of cancer treatment in humans.

PI_NAMEs: POLLACK, SETH M (contact)

PROGRAM_OFFICER_NAME: SORG, BRIAN S

PROJECT_TERMS: Adaptive Immune System;Adoptive Cell Transfers;Aftercare;Alpha Virus;Animal Hospitals;Animal Model;Antigen Presentation;Antigen-Presenting Cells;Biological Assay;Biology;Biotechnology;Blood;cancer immunotherapy;Cancer Patient;cancer therapy;Cancerous;Canis familiaris;Categories;CD209 gene;CD4 Positive T Lymphocytes;Cells;Cellular Immunity;cellular transduction;Clinic;Clinical;clinical development;Clinical Trials;Collaborations;companion animal;Companions;cytokine;Dangerousness;delivery vehicle;Dendritic Cells;design;Disease;Disease remission;Disease-Free Survival;Dose;Elements;Endothelial Cells;Engineering;Experimental Models;Flow Cytometry;Formulation;Gene Delivery;Human;Immune;immune checkpoint;Immune checkpoint inhibitor;Immunity;Immunohistochemistry;Immunotherapy;Impairment;improved outcome;industry partner;Infiltration;Inflammatory;Inflammatory Response;Innate Immune System;Interleukin-12;Interleukin-12 Gene;intravenous administration;Investments;Kinetics;Lentivirus;Malignant Neoplasms;Methods;Modeling;mouse model;Movement;Necrosis;Neoadjuvant Therapy;neoplastic cell;novel;novel therapeutics;Oncology;Patients;Peripheral Blood Mononuclear Cell;Phenotype;Population;prevent;primary endpoint;Production;Quality of life;recruit;Regulatory T-Lymphocyte;RNA;RNA delivery;RNA replication;Sampling;Serum;single-cell RNA sequencing;Soft Tissue Neoplasms;Soft tissue sarcoma;Solid Neoplasm;Sorting;Specificity;Specimen;synergism;System;T cell infiltration;T cell receptor repertoire sequencing;T cell response;T-Lymphocyte;targeted delivery;Testing;Therapeutic;therapeutically effective;transcriptome sequencing;tumor;Tumor Immunity;tumor immunology;tumor microenvironment;Up-Regulation;vector;Veterinarians;Viral;Virus

PROJECT_TITLE: Novel IL-12 Gene Delivery Vehicles for Transformation of Solid Tumors


ADMINISTERING_IC: AG

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Arthritis;Assistive Technology;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Networking and Information Technology R&D (NITRD);Osteoarthritis;Patient Safety;Physical Activity;Physical Rehabilitation;Rehabilitation;Telehealth

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: BARRON ASSOCIATES, INC.

ORG_STATE: VA

PHR: PROJECT NARRATIVE The proposed Knee Biofeedback Rehabilitation Interface for Game-based Home Therapy (“KneeBRIGHT”) system aims to motivate patients with knee osteoarthritis to engage in regular muscle strengthening exercise through an engaging, EMG-driven video game therapy. KneeBRIGHT will enhance rehabilitation by: (1) increasing functional recovery through physical practice of evidence-based exercise routines; (2) promoting adherence through fun activities and real-time performance feedback; (3) providing a low-cost option for effective home therapy; (4) creating reliable tracking mechanisms for patient adherence and functional status; and (5) increasing access to care in remote, underserved areas.

PI_NAMEs: KREPKOVICH, EILEEN T. (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Address;Adherence;arthropathies;Biofeedback;Certification;Clinic;clinical practice;Clinical Trials;clinically relevant;Cloud Service;Combined Modality Therapy;comparison control;Computer software;Control Groups;control trial;cost;COVID-19 pandemic;dashboard;data dashboard;Degenerative polyarthritis;design;design verification;Development;Devices;disability;Documentation;effective therapy;Electrodes;electromyographic biofeedback;Electromyography;Equilibrium;evidence base;Evidence based practice;Exercise;exercise program;exercise regimen;exercise rehabilitation;experience;Feedback;functional improvement;functional outcomes;functional status;Health Insurance Portability and Accountability Act;Health Services Accessibility;Home;Home environment;improved;innovation;Insurance;Knee;Knee Osteoarthritis;Label;Marketing;Modeling;Monitor;Motivation;New Device Approvals;next generation;Notification;Outcome;Pain;Pain Measurement;pain reduction;Participant;Patient Compliance;patient engagement;Patients;Performance;Phase;Physical Function;Physical therapy;Production;programs;Protocols documentation;prototype;Provider;Psychology;Public Health;quadriceps muscle;Questionnaires;Randomized;Randomized Controlled Clinical Trials;Randomized, Controlled Trials;Recovery of Function;Regimen;Rehabilitation therapy;remote patient monitoring;Research Personnel;Resistance;Risk;Safety;Secure;sensor;Software Design;Specific qualifier value;strength training;Study models;success;Support System;System;Technology;telehealth;Teletherapy;Testing;Time;tool;Training;Translational Research;Travel;trend;underserved area;United States;usability;Validation;Video Games;virtual world;walking speed;web app;wireless

PROJECT_TITLE: Knee-Biofeedback Rehabilitation Interface for Game-based Home Therapy (KneeBRIGHT)


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Project Narrative The proposed work aims to understand the organization and function of the brain systems that support human memory and to illuminate the nature of memory disorders. We are studying individuals with memory impairment due to brain injury, and we are studying healthy volunteers using functional magnetic resonance imaging (fMRI). The neuropathology has been thoroughly documented quantitatively with MRI. Memory problems are commonly reported in conjunction with neurological and psychiatric illness and are a significant issue in veterans’ health. Improved knowledge about how memory works, and about how memory fails after injury or disease, lays a foundation for the development of interventions to help diagnose, treat, and prevent the diseases that affect memory, including Alzheimer’s disease. Better knowledge about how memory works, and how to measure it, also provides a foundation for improved assessment of memory impairment, which is increasingly significant in Veterans returning from combat and in aging Veterans.

PI_NAMEs: SQUIRE, LARRY R (contact)

PROJECT_TERMS: Academy;Affect;Aging;Alzheimer's Disease;Anatomy;Animal Model;Autobiography;Award;Awareness;Bilateral;Biological;Book Chapters;Books;Brain;brain based;Brain Diseases;Brain Injuries;career;Code;Cognition;Collaborations;Collection;combat;Confusion;Conscious;Diagnosis;Disease;distinguished professor;Doctor of Philosophy;Early Diagnosis;Educational Curriculum;Epilepsy;Episodic memory;Event;experience;Eye Movements;Face;Faculty;Familiarity;Foundations;Functional Magnetic Resonance Imaging;Funding;Future;Grant;Health;health science research;healthy volunteer;Hippocampus;Human;human model;Impairment;improved;indexing;Individual;Injury;insight;Internet;Investigation;journal article;Knowledge;Learning;Lesion;life history;long term memory;Magnetic Resonance Imaging;Measures;medial temporal lobe;Medicine;member;Memory;Memory Disorders;Memory impairment;memory recognition;Mental disorders;military veteran;Mind;National Institute of Mental Health;Nature;Nervous System Disorder;Neurologic;Neurons;neuropathology;Neuropsychology;Neurosciences;nonhuman primate;normal aging;novel;Operative Surgical Procedures;Paper;Patients;Peer Review;Population;prevent;Prevention;Principal Investigator;procedural memory;programs;Progress Reports;Psyche structure;Psychology;Publications;Rattus;Reporting;Research;Research Activity;Research Personnel;response;Rodent;Role;sample fixation;Sampling;Scanning;Science;Scientist;Series;Specialist;Structure;Support System;System;Techniques;Testing;therapy development;Unconscious State;United States National Academy of Sciences;United States National Institutes of Health;Veterans;Work

PROJECT_TITLE: CSR&D Research Career Scientist Award

STUDY_SECTION: RCSR

STUDY_SECTION_NAME: Research Career Scientist[RCSR]


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

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE: Many promising drug candidates fail to advance clinically due to issues with systemic toxicity, the inability to appropriately reach target tissues/cells, and improper synergy with combinatorial partners. We take a unique approach to overcome these limitations using bottlebrush polymer prodrugs that allow for tissue-selective drug release, precise delivery of combinatorial therapeutics at specific ratios, and cell-selective targeting through tunable antibody-brush polymer conjugates. In addition, we adapt this technology to achieve real-time MRI imaging of cellular and molecular processes that can be used to non-invasively evaluate pharmacological efficacy.

PI_NAMEs: JOHNSON, JEREMIAH ALLEN (contact)

PROGRAM_OFFICER_NAME: TATA, DARAYASH B

PROJECT_TERMS: Acetals;Address;Affinity;anti-PD-L1;anti-tumor immune response;Antibodies;Antibody-drug conjugates;Architecture;attenuation;Binding;Biodistribution;Biological Availability;Bromodomains and extra-terminal domain inhibitor;cancer cell;CASP3 gene;Cell Death;Cells;cellular imaging;Characteristics;checkpoint inhibition;checkpoint therapy;Chemistry;chemotherapy;Clinical;clinically relevant;combinatorial;Combined Modality Therapy;Companions;Contrast Media;Cytotoxic T-Lymphocytes;cytotoxicity;Data;Desmoplastic;Development;Disease;Disulfides;drug candidate;Drug Delivery Systems;Drug Kinetics;Drug Synergism;Drug toxicity;effective therapy;Elements;Enhancers;enzyme activity;epigenetic therapy;esterase;Esters;Event;Fc Receptor;gemcitabine;Gene Expression;Generations;Granzyme;image guided;Immune checkpoint inhibitor;immunogenic cell death;Immunotherapy;improved;In Vitro;in vivo;in vivo imaging;Individual;Induction of Apoptosis;Intervention;invention;irinotecan;Lead;Lymphoid Tissue;macromolecule;Magnetic Resonance Imaging;Malignant neoplasm of pancreas;Mediating;Metals;Methodology;Methods;Mitomycin C;Modeling;Molecular;mouse model;Mucin 1 protein;neoplastic cell;novel strategies;Outcome;Paclitaxel;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Penetration;Peptides;Pharmaceutical Preparations;pharmacologic;Polymers;Population;Process;Prodrugs;programmed cell death ligand 1;programs;Property;Proteins;ratiometric;receptor binding;Reporter;Reporting;Resistance;response;Shapes;SN-38;standard of care;Stromal Cells;Structure-Activity Relationship;synergism;System;systemic toxicity;T-Cell Activation;T-Lymphocyte;targeted delivery;targeted treatment;Technology;Tertiary Protein Structure;Testing;Therapeutic;therapy development;therapy outcome;Time;Tissues;Toxic effect;toxic metal;Treatment Efficacy;treatment response;tumor;Tumor Burden;tumor growth;Tumor Immunity;tumor microenvironment;Work

PROJECT_TITLE: Bottlebrush polymer prodrugs for targeted delivery of combination therapies and in vivo imaging of pharmacological response

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


ORG_CITY: RICHMOND

ORG_DEPT: PHYSIOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

PHR: PROJECT NARRATIVE  Information from this project will help the design of novel therapeutic interventions targeting regulatory points in cardiac palmitoylome. 1

PI_NAMEs: TSENG, GEA-NY  (contact);UEBERHEIDE, BEATRIX MAGDALENA

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Address;Affect;Area;Binding;Bioinformatics;Biometry;Canis familiaris;Cardiac;Cardiac Myocytes;Cardiomyopathies;Case Study;Cell membrane;Cell Nucleus;cell type;Cysteine;Cytosol;Data;Data Analyses;design;Detection;Development;Disease;enzyme substrate;Enzymes;experimental study;Genetic Transcription;genetic variant;Glues;Health;Heart;high resolution imaging;Human;Hydrophobicity;Image;Impairment;Integral Membrane Protein;Ion Channel;junctophilin;Link;Location;Membrane Microdomains;multitask;Muscle Cells;novel therapeutic intervention;Palmitic Acylation Site;palmitoylation;Pathogenicity;Patients;Post-Translational Protein Processing;Prevalence;prevent;protein distribution;protein function;Protein S;protein transport;Proteins;Proteome;Proteomics;Rattus;Regulation;Research;Role;RyR2;Sarcoplasmic Reticulum;Side;single molecule;Structure;Sulfhydryl Compounds;Testing;Variant

PROJECT_TITLE: Protein S-Palmitoylation in the Heart: Function and Regulation in Health and Disease

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


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

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project narrative Postoperative delirium is a common, costly, and potentially fatal complication that is strongly associated with aging, Alzheimer’s disease (AD), and other forms of dementia. The goal of the project is to establish the role of neural circuits affected early in AD and aging on prodromal cognitive function and risk of postoperative delirium using clinically relevant behavioral testing paradigms in a rat model of AD. The proposed studies implement chemogenetic tools to identify specific therapeutic targets for POD intervention.

PI_NAMEs: VINCENT, KATHLEEN FRANCES (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acute;Address;Adult;Advisory Committees;Affect;Age;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid;Anesthesia procedures;Anesthetics;Animals;Attention;Attentional deficit;Attenuated;Automobile Driving;Award;Basic Science;behavior test;Behavioral;Brain;Brain Pathology;brain tissue;career;career development;career networking;Chronic;Clinical;Clinical Research;clinically relevant;Cognitive deficits;cognitive function;cognitive recovery;cognitive testing;Communication;Communities;Complication;Confusion;cost;Curiosities;Dementia;Development;Development Plans;dopaminergic neuron;Elderly;Environment;Functional disorder;General Anesthesia;General anesthetic drugs;General Hospitals;Genetic;Genetic Techniques;Goals;Grant;Healthcare;Histopathology;Hospitalization;Hour;Human;Impairment;inattention;insight;Intervention;Lead;Linear Models;locus ceruleus structure;Massachusetts;Mediating;medical schools;Mentors;Mentorship;mortality risk;neural circuit;Neurocognitive;Neurons;neuropathology;noninvasive brain stimulation;noradrenergic;novel;novel therapeutics;Operant Conditioning;Outcome;Pathologic;Pathology;Phase;Positioning Attribute;Postoperative Complications;postoperative delirium;pre-clinical;Pre-Clinical Model;prevent;prodromal Alzheimer's disease;programs;Rattus;Reaction Time;Research;Research Personnel;Risk;Rodent Model;Role;Severities;skills;statistics;sustained attention;Symptoms;tau aggregation;tau Proteins;Techniques;Testing;Therapeutic Intervention;therapeutic target;Time;tool;touchscreen;Training;transgenic model of alzheimer disease;Transgenic Organisms;Translational Research;Unconscious State;Variant;Ventral Tegmental Area;Viral;Work;Writing

PROJECT_TITLE: Neural Circuits Underlying Post-operative Delirium in Early Stage Alzheimer's Disease

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development Facilitating The Transition to Independence Study Section[AGCD-1]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Social Determinants of Health;Substance Misuse

ORG_CITY: SALT LAKE CITY

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Life expectancy in the US has not kept pace with other countries recently due to the rise in mortality related to drug overdose, suicide, and alcohol as well as stalled progress in preventing cardiometabolic mortality. This study uses two longitudinal samples with twenty years of follow-up merged with rich place-based data to understand how structural, social, built, and environmental features prospectively affect individual-level substance misuse, mental health, cardiometabolic health, and mortality. This comprehensive research effort will produce novel evidence to support the development of effective place-based interventions.

PI_NAMEs: CURTIS, DAVID STUART (contact)

PROGRAM_OFFICER_NAME: JAIN, KRITI MUNJAL

PROJECT_TERMS: Address;Adult;Affect;Age;aged;Air;Alcohols;Area;Attention;Birth Certificates;Black race;built environment;cardiometabolism;Cardiovascular Diseases;Cessation of life;college;Communities;Complex;Country;County;Data;Data Set;Death Records;design;Development;Diabetes Mellitus;Disadvantaged;Economic Conditions;Enrollment;Environment;Equation;Family;Floods;follow-up;geographic difference;Health;Health behavior;health disparity;improved;Individual;innovation;insight;Intervention;Investigation;Knowledge;Licensing;Life Expectancy;Link;Literature;Longitudinal Studies;Measures;Mediating;Medical;Mental Health;Methods;middle age;Modeling;Morbidity - disease rate;mortality;mortality disparity;novel;obesogenic;Outcome;Overdose;overdose death;Pathway interactions;Persons;Pharmaceutical Preparations;Physical activity;Population;Population Database;Premature Mortality;prescription opioid;prevent;Process;prospective;psychosocial;Records;Research;Resources;Risk;Role;Sampling;social;social capital;social norm;social organization;Socioeconomic Status;socioeconomics;Statistical Methods;substance misuse;Suicide;Surveys;Survival Analysis;synthetic opioid;System;Testing;Time;trend;Unemployment;United States;urban area;Utah;walkability

PROJECT_TITLE: Area-level Socio-economic Conditions and Individual-level Health and Mortality: Exploring Place-Based Mechanisms and Individual-level Psychosocial Processes


NIH_SPENDING_CATS: Brain Disorders;Neurosciences

ORG_DEPT: PATHOLOGY

PHR: PROJECT NARRATIVE This study will determine how a novel immune cell type that resides in the protective linings of the brain impacts brain development and healing after injury. We will test the signals that these immune cells produce, the targets of these signals, and how they ultimately promote connections between brain nerve cells.

PI_NAMEs: MOLOFSKY, ANNA V;MOLOFSKY, ARI B (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Adult;Area;autism spectrum disorder;Automobile Driving;Behavior;Behavioral;Blood - brain barrier anatomy;Blood Vessels;Brain;Brain Injuries;brain parenchyma;Brain region;brain remodeling;brain repair;Cell Physiology;Cell Survival;cell type;Cells;cellular targeting;Coculture Techniques;Communication;cytokine;Data;Defect;Development;Electrophysiology (science);Fibroblasts;Flow Cytometry;GABA Receptor;gain of function;Genetic;Genetic Transcription;Goals;Grant;Growth;healing;Heterogeneity;Image;Image Cytometry;Immune;immune cell infiltrate;Immune signaling;Immunity;Immunology;Immunophenotyping;Impairment;In Vitro;in vivo;Inflammation;Inhibitory Synapse;Injury;injury recovery;Interleukin-13;interleukin-13 receptor;Interleukin-4;Interleukins;Life;loss of function;Lymphocyte;Lymphocyte Function;Lymphoid Cell;Macrophage;Mediating;memory recall;Meningeal;Meninges;Microglia;Modeling;Molecular;Morphology;Mus;Myelogenous;Neurodevelopmental Disorder;Neuroglia;neuroinflammation;Neurons;Neurosciences;novel;novel therapeutic intervention;Organ;Pathologic;Phenocopy;Physiology;Play;postnatal;postnatal period;Production;receptor;recruit;Regulation;repaired;response;Role;Schizophrenia;Signal Transduction;single cell sequencing;Slice;social;Social Behavior;Source;Stromal Cells;Supporting Cell;Synapses;synaptic function;synaptogenesis;System;Testing;Three-Dimensional Imaging;Tissues;transcriptome;Work;wound healing

PROJECT_TITLE: Meningeal type 2 immunity in cortical synapse remodeling during brain development and injury

STUDY_SECTION: CMBG

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


NIH_SPENDING_CATS: Cancer;Genetics;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PROJECT NARRATIVE Neuroblastoma is the most common solid malignant tumor of childhood and accounts for approximately 15% of all deaths due to pediatric cancers. High-risk neuroblastoma is often characterized by the expression of amplified MYCN for which no direct inhibitors have yet been generated. We propose to take advantage of the increased requirement for protein synthesis in MYCN-amplified cells by exploring therapeutic inhibition of translation initiation using novel rocaglate derivatives that are expected to provide selective targeting of this process.

PI_NAMEs: GEORGE, RANI E. (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: 5' Untranslated Regions;addiction;analog;Apoptosis;Biogenesis;Biological Assay;Boston;cancer cell;Cell Cycle Progression;cell growth;Cell Line;Cell Proliferation;Cells;cellular targeting;Cessation of life;chemical synthesis;Chemistry;childhood cancer mortality;Childhood Solid Neoplasm;Clinical;clinical application;Closure by clamp;cytotoxic;cytotoxicity;Development;Digit structure;Disease;disorder risk;Dose;efficacy study;established cell line;Evaluation;Exhibits;Gene Expression;gene function;Genes;Genetic Transcription;Goals;Growth;high risk;in vivo;inhibitor;Libraries;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Messenger RNA;Modeling;MYCN gene;N-Myc Protein;nanomolar;neoplastic cell;Neuroblastoma;neuroblastoma cell;novel;novel strategies;novel therapeutic intervention;Oncogenes;Oncogenic;overexpression;patient derived xenograft model;Patients;Peptide Initiation Factors;pharmacologic;pre-clinical;premature;prevent;Process;Property;Protein Biosynthesis;protein expression;Protein Synthesis Inhibitors;Proteins;recruit;Regulation;Regulatory Element;Research Personnel;Resistance;response;ribosome profiling;Ribosomes;RNA;RNA Helicase;RNA immunoprecipitation sequencing;Role;scaffold;Scanning;Solid;success;Sympathetic Nervous System;Testing;Therapeutic;therapeutic target;Transcript;transcription factor;Translation Initiation;translational potential;Translational Repression;Translations;tumor;Universities;Untranslated Regions;Validation

PROJECT_TITLE: Translation initiation as a therapeutic target in neuroblastoma


ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE A novel class of dietary-derived nitro-fatty acid hybrids having dual nitrate ester (R-ONO2) and nitroalkene (R- NO2) substituents (NO2-ONO2-FA) is proposed to promote vasodilation and inhibit cardiovascular inflammatory responses via both cGMP-dependent and cGMP-independent signaling actions, establishing a safe pharmacological strategy targeting inflammatory-related CVD.

PI_NAMEs: FAZZARI, MARCO  (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: Alkylation;Alternative Therapies;Anions;Anti-Inflammatory Agents;Antioxidants;Attenuated;Binding;Biochemical;Blood Vessels;Carbon;Cardiovascular Diseases;cardiovascular effects;Cardiovascular system;Cause of Death;Cell Adhesion Molecules;Cell Proliferation;Cessation of life;Charge;Chemicals;Chylomicrons;Circulation;Clinical;Clinical Data;Clinical Research;Conjugated Linoleic Acids;Consumption;Cyclic GMP;Cysteine;cytokine;Dairy Products;Data;Development;dietary;dietary constituent;Dietary Intervention;Digestion;Drug Kinetics;Drug Targeting;Electrons;endothelial dysfunction;Environment;Enzymes;epidemiology study;Esters;Fatty Acids;Foundations;Fruit;Gene Expression;Generations;Genes;genetic regulatory protein;Goals;good diet;Guanylate Cyclase;Heme;Hybrids;hypertensive;In Vitro;in vivo;Incidence;Individual;Inflammation;Inflammatory;Inflammatory Response;Injury;insight;Intestinal Absorption;Ischemia;Isosorbide Mononitrate;lipid mediator;Meat Products;Mediating;Mediator;Metabolic;microbiome;mortality;Myocardial;NBL1 gene;nitrated conjugated linoleic acid;Nitrates;nitration;Nitrites;nitroalkene;Nitrogen Dioxide;Nitrogen Oxides;Nitroglycerin;novel;novel drug class;Organic Synthesis;Outcome;Pathologic;Peroxidases;pharmacologic;Pharmacology;Post-Translational Protein Processing;pre-clinical;Prodrugs;Reaction;Reactive Oxygen Species;Reporting;Research;response;Route;Salivary;Signal Transduction;small molecule;Source;stem;Stomach;Stress;Testing;Transcription Regulatory Protein;Triglycerides;Unsaturated Fatty Acids;Vasodilation;Vegetables

PROJECT_TITLE: Nitro-nitrate fatty acid derivatives as novel cGMP-dependent and cGMP-independent signaling mediators


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Biodefense and Related Countermeasures;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Dementia;Emerging Infectious Diseases;Estrogen;Infectious Diseases;Neurodegenerative;Neurosciences;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID);Women's Health Research

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE  This project will address a critical emerging public health concern by elucidating the cerebrovascular and microstructural brain changes following COVID-19 infection that may predispose aging adults to long-term cognitive impairment or neurodegenerative changes. By examining how COVID-19-related brain and cognitive measures differ by sex and are modified Alzheimer’s disease genetic risk and pathology, results are expected to help identify individuals at greatest risk for adverse COVID-19-related neurological outcomes and to guide personalized approaches for risk assessment and treatment. This project will support the mission of the NIH by clarifying how COVID-19 impacts neurobiological aging and may amplify an already grave public health crisis of age-related cognitive decline and dementia.

PI_NAMEs: REAS, EMILIE T. (contact)

PROGRAM_OFFICER_NAME: FRANKOWSKI, DAVID WITT

PROJECT_TERMS: 2019-nCoV;Acceleration;ACE2;Acute;acute COVID-19;Adult;Age;age related;Age-associated memory impairment;aged;Aging;aging population;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Anti-Inflammatory Agents;apolipoprotein E-4;Attention;Binding;biomarker identification;Blood;Blood - brain barrier anatomy;Blood brain barrier dysfunction;blood-brain barrier permeabilization;Brain;brain abnormalities;brain dysfunction;brain health;Brain Injuries;brain tissue;Central Nervous System;cerebrovascular;Cerebrovascular Disorders;Cognitive;Cognitive deficits;cognitive function;cognitive recovery;cognitive testing;comorbidity;Complex;Confusion;contrast enhanced;COVID-19;COVID-19 impact;COVID-19 mortality;COVID-19 pandemic;COVID-19 patient;COVID-19 risk;COVID-19 sequelae;COVID-19 severity;COVID-19 survivors;Dementia;Diffusion;Diffusion Magnetic Resonance Imaging;Disease;Drops;Endothelial Cells;Estrogens;executive function;Exhibits;Extravasation;Genetic;Genetic Risk;genetic risk factor;Gonadal Steroid Hormones;hazard;high risk population;Hippocampus;hormone regulation;human old age (65+);Hyperactivity;Immune;Immune response;Impaired cognition;Individual;Infection;Infiltration;Inflammation;Inflammatory;Injury;Investigation;late life;Long COVID;long term consequences of COVID-19;Magnetic Resonance Imaging;Measures;Medial;Mediating;Memory;men;Menopause;mental state;Methods;Mission;Modification;multimodal neuroimaging;Nerve Degeneration;nerve injury;Neurobehavioral Manifestations;Neurobiology;neuroimaging;neuroinflammation;Neurologic;Neurologic Effect;neurologic sequelae of COVID-19;Neurologic Symptoms;Neurological outcome;Neurons;neuropathology;neurovascular;older adult;Outcome;outcome prediction;Participant;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;Permeability;personalized approach;Plasma;post SARS-CoV-2 infection;pre-clinical;Predisposition;preservation;Public Health;Reporting;Research;respiratory virus;response;Restriction Spectrum Imaging;Risk;Risk Assessment;Risk Estimate;Risk Factors;Role;SARS-CoV-2 infection;severe COVID-19;sex;Sex Differences;Structure;Symptoms;synergism;tau-1;Techniques;Testing;Testosterone;Time;tool;United States National Institutes of Health;Vascular Diseases;Viral;Woman

PROJECT_TITLE: COVID-19-related blood-brain barrier and microstructural brain injury; Sex differences and synergy with Alzheimer's disease risk

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Cardiovascular;Hypertension

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project narrative: Nitric oxide (NO) regulates vascular tone and blood pressure; however, the process of vascular NO metabolism is not well understood. We have shown that the recently discovered globin, Cytoglobin (Cgb), is expressed in smooth muscle and functions to regulate NO metabolism in the vessel wall, in turn, modulating vascular tone. We will determine how the NO degrading and antioxidant properties of Cgb control NO and redox metabolism in normal and hypertensive vessels, and how this in turn regulates vessel tone and blood pressure in normal physiology and cardiovascular disease, leading to development of novel therapeutics to reverse vascular disease.

PI_NAMEs: ZWEIER, JAY LOUIS (contact)

PROJECT_TERMS: Accounting;Affect;Angiotensins;Antioxidants;Biological Assay;Biological Availability;Blood Pressure;Blood Vessels;Cardiovascular Diseases;Cardiovascular Physiology;Cardiovascular system;Computer Models;Cytochromes b5;Data;Development;Diffusion;Dioxygenases;Disease;Endothelium;Evaluation;Gene Modified;Globin;Grant;heart function;Hemeproteins;Heterozygote;Histology;Hypertension;hypertensive;in vivo;in vivo evaluation;inhibitor;insight;Knockout Mice;Knowledge;mathematical model;Measurement;Measures;Mediating;Mediator;Metabolism;mimetics;mouse model;Mus;Nitrates;Nitric Oxide;Nitric Oxide Synthase;novel;novel therapeutic intervention;novel therapeutics;overexpression;Oxidation-Reduction;Oxidoreductase;Peroxonitrite;Physiological;Physiology;preservation;Process;programs;Property;Publishing;Reaction;Regulation;Relaxation;Reporting;Research;Resistance;response;Role;Smooth Muscle;Soluble Guanylate Cyclase;Spin Trapping;Superoxide Dismutase;Superoxides;Support System;Systemic blood pressure;Testing;Thick;Vascular Diseases;Vascular Smooth Muscle

PROJECT_TITLE: Role of Cytoglobin in the Regulation of Vascular Tone


NIH_SPENDING_CATS: Behavioral and Social Science;Building Research Capacity at Institutions with Limited NIH Funding;Social Determinants of Health

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

PHR: NARRATIVE The overall objective of the Summer Undergraduate Research Experience in Environmental Health Sciences (SURES) program is to use a research-intensive approach for introducing students from the impoverished region of Appalachia to the multidisciplinary nature of environmental sciences and opportunities for pursuing relevant careers. Exceptional training in a wide variety of research areas working with interdisciplinary collaborative research groups who are housed in multiple departments and colleges is provided. In addition, seminars, outreach opportunities and interactive workshops are designed to prepare students for successful, environmental health related careers.

PI_NAMEs: PEARSON, KEVIN JOSEPH;SWANSON, HOLLIE ISABEL (contact)

PROGRAM_OFFICER_NAME: HUMBLE, MICHAEL C

PROJECT_TERMS: Address;Affect;Appalachian Region;Area;career;citizen science;climate change;cohort;Collection;college;Communities;community building;Critical Thinking;design;Development;Doctor's Degree;Economics;Education;Educational workshop;Elevator;Engineering;Environment;Environmental Exposure;Environmental Health;Environmental Science;Ethics;Evaluation;Exercise;experience;experimental study;Faculty;faculty mentor;Family member;Fellowship;Film;Funding;Future;global health;Goals;Government;hands on research;Health Professional;health science research;improved;Individual;Industry;Institution;interest;Interview;Kentucky;Laboratories;Lead;Life;Measures;member;Mentors;Mission;multidisciplinary;National Institute of Environmental Health Sciences;Nature;novel;Oral;Outcome;outreach;Paint;Participant;patient engagement;peer;peer coaching;Personal Satisfaction;Persons;Play;podcast;Population Heterogeneity;Positioning Attribute;Postdoctoral Fellow;posters;Poverty Areas;Professional Competence;programs;Publications;Questionnaires;recruit;Reporting;Research;research facility;Research Personnel;Research Project Grants;Research Training;Role;Safety;Science;Scientist;skills;social;Speech;STEM field;student mentoring;student participation;student retention;Students;success;summer program;summer research;supportive environment;Surveys;Technology;Training;Training Programs;undergraduate education;undergraduate research;undergraduate research experience;undergraduate student;Underrepresented Students;United States;Universities;Work

PROJECT_TITLE: Summer Research in Environmental Health Sciences


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Genetics;Human Genome;Mental Health;Neurosciences;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECTIVE NARRATIVE The objective of this grant is to study the detailed molecular and cellular mechanisms by which different forms of chronic stress alter specific types of neurons within the brain's reward circuitry. We focus on changes at the chromatin—or epigenetic—level as mediators of particularly long-lasting effects of stress exposure. These studies will provide new information concerning how chronic stress causes lifelong changes in stress susceptibility and, in turn, identify novel leads toward the development of improved treatments for stress- related disorders in humans.

PI_NAMEs: NESTLER, ERIC J. (contact)

PROGRAM_OFFICER_NAME: LEINWAND, SARAH GOLDBERG

PROJECT_TERMS: Adult;Affect;Anxiety Disorders;Applications Grants;Autopsy;Behavioral;behavioral response;Biological Assay;Biology;Brain;Brain region;brain reward regions;Categories;cell type;Cells;Chromatin;chromatin modification;Chromatin Structure;Chronic stress;Cicatrix;Clinical Trials;clinically relevant;Data;Data Set;Depressed mood;desensitization;Development;Diagnosis;Diagnostic tests;DSM-V;early life stress;Ensure;Enzymes;Epigenetic Process;expectation;Exposure to;Female;Gene Expression;gene network;Genes;Genetic Transcription;genome wide association study;genome-wide;Genomic Segment;Goals;Grant;histone demethylase;Histone H3;histone methyltransferase;histone modification;Histones;Human;improved;Individual;inhibitor;innovation;insight;Investigation;knock-down;Knowledge;Laboratories;Life;Link;male;Malignant Neoplasms;Maps;Measures;Mediating;Mediator;Mental Depression;Methyltransferase;Modeling;Modification;Molecular;Molecular Target;Motivation;Mus;National Institute of Mental Health;neural;Neurons;next generation sequencing;novel;Nucleus Accumbens;overexpression;Patients;Play;Post-Traumatic Stress Disorders;Predisposition;Procedures;Proteomics;Regulation;Research;resilience;response;reward circuitry;Rewards;Role;screening;Signal Transduction;Stress;stress disorder;stress related disorder;stress resilience;Stress Tests;Testing;Time;Tissues;transcriptome sequencing;transcriptomics;translational potential;Viral;Weaning;Work

PROJECT_TITLE: Epigenetic Mechanisms of Chronic Stress Action

STUDY_SECTION: MCNP

STUDY_SECTION_NAME:
Molecular and Cellular Neuropharmacology Study Section
[MCNP]


ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: NARRATIVE Our primary research goal is to understand the function of long non-coding RNAs in the cardiovascular system. In this project, we will examine whether the large intergenic non-coding RNA called lincRNAp21 can alleviate pressure overload induced cardiac hypertrophy, a medical condition that is a leading cause of death worldwide and highly relevant to the mission of the NIH. Our studies using mutant mouse models are designed to be translated into novel therapeutic strategies to treat patients with hypertrophic cardiomyopathy.

PI_NAMEs: WANG, DA-ZHI  (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: adeno-associated viral vector;adeno-associated virus 9 delivery;Affect;Apoptosis;Area;Atherosclerosis;Biochemical;Biological;Biological Process;Cardiac;Cardiac Myocytes;cardiac regeneration;cardiogenesis;Cardiomyopathies;Cardiovascular Diseases;Cardiovascular system;Cause of Death;Cell Nucleus;Cell Proliferation;Code;Cyclin-Dependent Kinase Inhibitor 3;Data;Defect;Dependovirus;design;Development;differential expression;Disease;effective therapy;epigenetic regulation;gain of function;Gene Delivery;Gene Expression;Gene Expression Regulation;gene repression;Genes;Genetic;Genetic Engineering;Genetic Transcription;Genome;Goals;Growth;Heart;Heart Diseases;heart function;Heart Hypertrophy;Human;Hypertrophic Cardiomyopathy;improved;in vivo;interest;Investigation;ischemic cardiomyopathy;knock-down;Length;Link;loss of function;Medical;MicroRNAs;Mission;model design;Molecular;Molecular Target;molecular targeted therapies;mouse model;Mus;mutant mouse model;Mutant Strains Mice;Myocardial Infarction;Natural regeneration;new therapeutic target;novel;novel therapeutic intervention;Nuclear Protein;Nucleotides;Organism;overexpression;Pathologic;Pathologic Processes;Patients;Physiological;Physiological Processes;Play;pressure;Process;Proliferating;protein function;Proteins;Regulation;Reporting;Research;response;RNA;Role;screening;Stress;Testing;Therapeutic;therapeutic evaluation;therapeutic target;therapeutically effective;TP53 gene;Transcript;transcriptome sequencing;Translating;Translational Repression;United States;United States National Institutes of Health;Untranslated RNA;Vascular Diseases;Vascular remodeling

PROJECT_TITLE: lncRNA Function and Mechanisms during Cardiac Development and Disease


ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Dyads are heart muscle structures that coordinate cardiomyocyte contraction. Dyad’s structure and function is disturbed in diseased heart muscle cells, We will study mechanisms responsible for maintaining normal dyad structure and function, and mechanisms that alter dyad structure and function in heart disease.

PI_NAMEs: PU, WILLIAM TSWENCHING (contact)

PROJECT_TERMS: Architecture;Arrhythmia;Binding;Cardiac;cardiac muscle disease;Cardiac Myocytes;Cell membrane;Cells;Coupled;Coupling;Data;Development;Diffusion;Dilated Cardiomyopathy;Disease;Endoplasmic Reticulum;extracellular;Functional disorder;Heart;Heart Diseases;Heart failure;Homeostasis;Human;in vivo;induced pluripotent stem cell;Inherited;insight;Link;Maintenance;Mediating;Membrane;Molecular;Mus;muscular structure;Mutation;Myocardial dysfunction;Myocardium;nanoscale;Nanostructures;novel;overexpression;Pathogenesis;Pattern;Positioning Attribute;preservation;pressure;Proteins;Proteomics;Regulation;Relaxation;response;Risk;Ryanodine Receptor Calcium Release Channel;Sarcomeres;Sarcoplasmic Reticulum;Signal Transduction;Structure;Testing;transmission process;Tubular formation;Work

PROJECT_TITLE: CMYA5 regulation of cardiac dyad structure and function