ADMINISTERING_IC: AT

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Cancer;Complementary and Integrative Health;Contraception/Reproduction;Dietary Supplements;Estrogen;Fibroid Tumors (Uterine);Natural Products;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Uterine Cancer;Women's Health Research

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Relevance to Public Health Botanical dietary supplements are widely consumed for the prevention and treatment of gynecological conditions. Deciphering whether popular dietary supplements contain progesterone-like molecules capable of regulating progesterone receptor signaling is critical to ensuring their safe and effective use for women’s health.

PI_NAMEs: BURDETTE, JOANNA E (contact);MURPHY, BRIAN THACHER

PROGRAM_OFFICER_NAME: STILL, PATRICK COLBY

PROJECT_TERMS: Address;Agonist;Alternative Therapies;Androgen Receptor;Animal Model;antagonist;Area;Awareness;Basic Science;Benign;Binding;Biological;Biological Assay;Botanical dietary supplements;Botanicals;Cells;Cellular Assay;Chemicals;chemo-dietary;Chromatography;Computer Models;Consumption;cost;cost effective;Data;dietary;dietary chemoprevention;dietary supplements;Disease;Dogwood;Elements;endometriosis;Ensure;Estrogen Receptors;experimental study;Family;Fibroid Tumor;Genetic Transcription;genome-wide;Glucocorticoid Receptor;Goals;Growth;Gynecologic;Health;Health Benefit;Herbal supplement;Hormones;improved;Knowledge;Ligands;Luciferases;Marketing;Measures;Mediating;member;Microfluidics;Modeling;Monitor;National Center for Complementary and Integrative Health;Natural Products;neglect;Nuclear Receptors;organ on a chip;Plants;Post-Translational Protein Processing;pre-clinical;Pre-Clinical Model;Premature Birth;prevent;Prevention;Progesterone;Progesterone Receptors;Progestins;Property;Public Health;Rattus;receptor;receptor binding;Receptor Signaling;Repression;Risk;Safety;Signal Transduction;Structure;Synthetic Progestogens;Technology;Testing;Therapeutic Uses;transcriptome sequencing;Trifolium pratense;Uterine Cancer;Uterine Diseases;Uterine hemorrhage;uterus hyperplasia;Vitex;Woman;Women's Health;Yucca

PROJECT_TITLE: Botanical derived progestins and their impact on women's health

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Prevention;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: NARRATIVE Randomized clinical trials of interventions to prevent and treat acute and chronic respiratory failure are the bedrock of evidence-based practice. However, there are several threats to the equity of such trials, including failures to enroll participants with similar characteristics to persons to whom the interventions would be applied, and the possibility that commonly used scoring systems for risk adjustment within such trials would perform inequitably across groups defined by race, ethnicity, or sex. This mid-career investigator award in patient- oriented research will take essential steps toward surmounting these challenges in the context of a multifaceted training program that will make the Principal Investigator a more effective mentor and team leader.

PI_NAMEs: HALPERN, SCOTT D (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Acute;Acute Lung Injury;Acute Respiratory Distress Syndrome;Address;advanced disease;American Heart Association;Award;behavior test;behavioral economics;Calibration;Cardiovascular system;career development;Caring;Characteristics;Chronic;clinical trial enrollment;Clinical Trials;Cohort Studies;comorbidity;Consent;Critical Care;Data;design;Detection;Discrimination;Disparity population;Early treatment;Effectiveness;Electronic Mail;Elements;Engineering;Enrollment;Equity;ethnic diversity;Ethnic Origin;Evidence based practice;experience;Faculty;Failure;Family Caregiver;financial incentive;Funding;Future;Goals;Grant;Growth;health equity;improved;indexing;Individual;Inequity;Infrastructure;innovation;insight;Intervention;intervention effect;Intervention Trial;Interview;Investments;Journals;K-Series Research Career Programs;Lead;Leadership;Learning;Lung;Measures;Medical;Medicine;meetings;Mentors;Mentorship;Methods;Mid-Career Clinical Scientist Award (K24);Midcareer Investigator Award in Patient-Oriented Research;Modeling;National Heart, Lung, and Blood Institute;Natural Language Processing;novel;Outcome;outcome prediction;palliative;participant enrollment;Patient Compliance;Patient Recruitments;Patient Representative;Patient-Focused Outcomes;Patients;Performance;Persons;Postdoctoral Fellow;prediction algorithm;predictive modeling;prevent;Prevention;Principal Investigator;professor;programs;Prospective Studies;Prospective, cohort study;provider adherence;Publishing;Qualitative Methods;Race;racial bias;racial diversity;randomized, clinical trials;recruit;Reporting;Research;Research Project Grants;Resources;Respiratory Failure;Risk;Risk Adjustment;Scientist;sex;skills;Smoking Cessation Intervention;statistics;Structure;student mentoring;System;systematic review;Talents;Technology;Testing;Text;Time;Training;Training Programs;Training Support;trial enrollment;United States National Academy of Sciences;United States National Institutes of Health;Visit;Work

PROJECT_TITLE: Improving the equity of RCTs among patients with acute and chronic respiratory failure

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(JA)]


ADMINISTERING_IC: AR

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Genetics;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CHICAGO

ORG_DEPT: PATHOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative: Self-renewal of adult stem cells is a fundamental property required for stem cell maintenance and tissue homeostasis. In this project, we will study hair follicle stem cells and their niche and investigate molecular mechanisms that govern the formation of the hair follicle stem cell compartment. Knowledge gained from the proposed study will provide new insights into the maintenance and aging of hair follicle stem cells and help to develop potential applications using hair follicle stem cells for regenerative medicine.

PI_NAMEs: YI, RUI  (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: adult stem cell;Affect;aged;Aging;Anatomy;Apoptosis;Architecture;Atlases;Binding;Biological Models;Cell Adhesion;Cell Aging;Cell Compartmentation;Cell Maintenance;cell motility;Cell Survival;cell type;Cells;Chromatin;Data Set;Dermis;Docking;Epithelium;exhaustion;Extracellular Matrix;FOXC1 gene;functional decline;Funding;Gene Expression;Genetic study;Genetically Engineered Mouse;Genome;genomic tools;Germ;Goals;Growth;Hair;Hair bulb structure;Hair follicle structure;Hair shaft structure;hallmarks of aging;Homeostasis;Image;Impairment;Individual;innovation;insight;Intercellular Junctions;intravital imaging;Knock-out;Knowledge;life span;Maintenance;Mammals;Mediating;migration;migratory population;Miniaturization;Modeling;Molecular;mouse model;mutant;next generation;novel;Pattern;Phase;Population;Premature aging syndrome;Process;progenitor;Property;Regenerative Medicine;Research;Resolution;Rest;self-renewal;single cell genomics;single-cell RNA sequencing;Site;Skin;spatiotemporal;Specific qualifier value;stem cell niche;stem cells;Testing;tissue regeneration;tissue stem cells;Tissues;Transcription Factor AP-1;Transcriptional Regulation;transcriptome;transcriptomics;transmission process

PROJECT_TITLE: Transcriptional regulation of skin stem cells and their niche


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Atherosclerosis;Biotechnology;Cardiovascular;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Liver Disease

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE The gene tribbles pseudokinase 1 (TRIB1) has been repeatedly identified by human genome-wide associations studies as a key regulator of cardiometabolic health in human, and in vivo mouse studies have highlighted the importance of hepatic Trib1 in these associations. However, despite the overwhelming human and experimental evidence of the importance of TRIB1, very little is known about its main mechanism of action in the liver. The proposed studies in this application will elucidate how hepatic TRIB1 regulates protein ubiquitination and degradation, determine the therapeutic benefit of increased hepatic TRIB1 activity in preclinical models of cardiometabolic disease, and leverage a unique human genetics data set to identify rare DNA variants in TRIB1 that can inform its therapeutic efficacy and safety.

PI_NAMEs: BAUER, ROBERT CLAYTON (contact)

PROGRAM_OFFICER_NAME: LOH, KATRINA SHUEH WEN

PROJECT_TERMS: 8q24;Address;adiponectin;Animal Model;Animals;Binding;biobank;Biological Assay;Biological Markers;Biology;Cardiometabolic Disease;cardiometabolism;CEBPA gene;Cell Line;Cholesterol;chronic liver disease;Complex;Consent;Coronary Arteriosclerosis;Cryoelectron Microscopy;Data;Data Set;DNA;Dyslipidemias;Enrollment;Enzymes;exome sequencing;experimental study;factor C;Family member;Fatty Liver;Gene Expression;Genes;Genetic;genetic association;genetic manipulation;Genetically Modified Animals;Genome;genome resource;genome wide association study;genomic locus;Glycosylated hemoglobin A;Goals;Health;Hepatic;Hepatocyte;hepatoma cell;High Density Lipoprotein Cholesterol;Human;human disease;Human Genetics;Human Genome;In Vitro;in vivo;Individual;insight;Knock-out;Knowledge;LDL Cholesterol Lipoproteins;Ligation;Link;lipid biosynthesis;lipid metabolism;Lipids;Liver;liver function;liver metabolism;loss of function;Measurement;Mediating;Metabolic;Metabolic Diseases;metabolic phenotype;Metabolic syndrome;Modeling;Molecular;Molecular Conformation;mortality;mouse model;Mus;mutant;Mutation;Myeloid Cells;non-alcoholic fatty liver disease;novel;overexpression;Pakistan;Participant;Pathway interactions;Phenotype;Physiology;Plasma;pleiotropism;Population;Pre-Clinical Model;preclinical study;Process;Proteins;Proteomics;Regulation;Resources;Role;Safety;somatic cell gene editing;Specificity;structural biology;Structure;Testing;Therapeutic;therapeutic evaluation;Thick;trait;transcription factor;transcriptome sequencing;translational potential;translational study;Treatment Efficacy;Triglycerides;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;Ultrasonography;Untranslated RNA;Variant;Very low density lipoprotein;Western World;Work

PROJECT_TITLE: Molecular Mechanisms of TRIB1 Regulation of Hepatic Metabolism

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: Los Angeles

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: Project Narrative How visual information is processed and transformed by cortical and subcortical pathways to generate visually guided behavior is a fundamental question for visual research. By focusing on the superior colliculus, a conserved visuomotor processing center, we will investigate how visual signals from two external input sources, primary visual cortex and ventral lateral geniculate nucleus, shape visual processing in superior colliculus neurons and impact related visual behaviors in a context-dependent manner. This research may help to provide potentially new information on general neural principles for our understanding of control and modulation of visually guided behaviors in normal subjects as well as in neurological and neuropsychiatric conditions.

PI_NAMEs: TAO, HUIZHONG WHIT (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Address;approach behavior;area striata;Attenuated;Behavior;Behavior Control;Behavioral;behavioral response;Cells;Data;Detection;excitatory neuron;Exhibits;Freezing;genetic approach;Geniculate body structure;Glutamates;Heterogeneity;information processing;insight;Lateral Geniculate Body;luminance;Maps;Mediating;Midbrain structure;Mus;nerve supply;neural;Neurologic;Neurons;neuropsychiatry;optogenetics;Pathway interactions;Pattern;pharmacologic;preference;Process;Property;Reaction;receptive field;Research;response;Retina;Role;screening;Shapes;Signal Transduction;Source;Stimulus;Structure;superior colliculus Corpora quadrigemina;Testing;Training;Transgenic Organisms;Visual;Visual Fields;visual information;visual motor;Visual Pathways;visual processing;visual receptive field;visual stimulus

PROJECT_TITLE: Processing and transformation of visual signals in the superior colliculus


ORG_CITY: ANN ARBOR

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative: Successful completion of the goals of this project will reveal how heme oxygenases regulate heme and carbon monoxide levels and protect cells against renal, cardiovascular and central nervous system pathologies induced by oxidative stress. Studies on Rev-Erb, which links the circadian clock to metabolism and inflammation, will help explain why abnormal circadian rhythms are associated with cancer, disturbances in the cell cycle and metabolic disorders. Our research on heme responsive motifs (HRMs) will reveal their multi-tier regulation of Rev-Erbβ and heme oxygenase-2.

PI_NAMEs: RAGSDALE, STEPHEN WILEY (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Address;Affect;Affinity;Antioxidants;Bilirubin;Biliverdine;Binding;Binding Sites;Biological Assay;Biological Availability;Biological Process;Carbon Monoxide;Cardiac;Cardiovascular Diseases;Cardiovascular system;Catalytic Domain;Cell Cycle;Cell Nucleus;Central Nervous System;Chemicals;Chemistry;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Co-Immunoprecipitations;Complex;Coupling;crosslink;Cytoprotection;Data;Deuterium;Diffusion;Disease;Distant;Disulfides;DNA;Environment;Enzymes;Exhibits;experimental study;Fluorescence;Fluorescence Anisotropy;Functional disorder;Gases;genetic corepressor;Genetic Transcription;Goals;heart function;Heat-Shock Proteins 90;Heme;heme a;heme oxygenase-1;heme oxygenase-2;Hemeproteins;Homeostasis;Human;Hydrogen;Hypoxia;In Vitro;Inflammation;Inflammatory Response;insight;Kidney;Kidney Diseases;Kinetics;Label;Length;Ligation;Link;Lipids;Liposomes;Malignant Neoplasms;Mammals;Mass Spectrum Analysis;Mediating;Membrane;Metabolic Diseases;Metabolism;meter;Methods;Mitochondria;Modeling;Molecular;Molecular Chaperones;Monitor;nanodisk;novel;Oxidation-Reduction;Oxidative Stress;Oxidative Stress Induction;Oxygenases;Pathology;Physiological;Play;Process;Property;protein complex;protein degradation;protein function;Proteins;Regulation;Reporter;Research;Rest;Role;sensor;Signal Transduction;Signaling Molecule;Source;Sulfhydryl Compounds;System;Tail;transcription factor;Transcription Repressor;Travel;Variant

PROJECT_TITLE: Heme-, Redox-, and CO-dependent Regulation of Heme Homeostasis

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Osteoporosis;Physical Injury - Accidents and Adverse Effects;Prevention

ORG_CITY: ROCHESTER

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Despite the prevalence and socioeconomic burdens of Osteoporosis and the associated fragility fractures, screening rates using standardized bone density scans are abysmal. This is attributed to disparities in access to screening, which can potentially be corrected with accessible pre-screening tools in physician offices and community clinics. Therefore, this proposal aims to develop an accessible, noninvasive optical vibrational spectroscopy tool to assess bone quality and fragility fracture risk.

PI_NAMEs: AWAD, HANI A;BERGER, ANDREW J (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: access disparities;Address;Affect;Age;Algorithms;American;Anatomy;arm;Biochemical;biomechanical test;Body mass index;bone;Bone Density;Bone Diseases;bone fragility;bone health;bone quality;bone strength;Cadaver;Classification;Clinic;Clinical Research;clinically relevant;community clinic;Complement;Data;data acquisition;Data Set;detector;Diagnosis;Diagnostic;Digital X-Ray;Distal;dosage;Dual-Energy X-Ray Absorptiometry;Early identification;Early Intervention;Economic Burden;Enrollment;falls;Female;Foundations;Fracture;fracture risk;fragility fracture;Funding;Future;global health;Hand;Heterogeneity;Hip Fractures;Hip region structure;Human;Human Volunteers;improved;in vivo;Incidence;instrumentation;irradiation;Libraries;Lighting;Limb structure;Location;male;Measurement;Measures;Medical center;men;Metacarpal bone;Methodology;Methods;Minerals;Monitor;Monte Carlo Method;mouse model;Mus;novel;Optics;Osteoporosis;osteoporotic bone;Patients;Peripheral;Phalanx;Photons;Physicians' Offices;Prevalence;primary care provider;Protocols documentation;Race;Radius Fractures;Raman Spectrum Analysis;Reporting;Reproducibility;response;Retrospective Studies;Risk;Risk Assessment;Risk Estimate;Safety;Sampling;scale up;Scanning;screening;Screening procedure;Sensitivity and Specificity;sex;Signal Transduction;Site;Skin;skin color;socioeconomics;soft tissue;Source;Spectrum Analysis;spine bone structure;Standardization;Thick;Tissues;tool;United States National Institutes of Health;Vertebral column;Visit;volunteer;Woman;Wrist;wrist fracture

PROJECT_TITLE: Raman spectroscopic platform for transcutaneous monitoring of bone quality

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Diabetes;Obesity;Osteoporosis;Physical Injury - Accidents and Adverse Effects

ORG_CITY: TROY

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: RENSSELAER POLYTECHNIC INSTITUTE

PHR: Project Narrative Bone fractures in type 2 diabetes cannot be accurately predicted by current bone density-based clinical tools as T2D patients exhibit normal to high bone mineral density. This project will establish Carboxymethyl-lysine (CML) as a new biomarker of T2D fracture and determine how the oxidation and glycation processes, associated with diabetes under obese and non-obese conditions, impact accumulation of CML and other Advanced Glycation Endproducts (AGEs) and enhance bone fragility. The results will provide new strategies to diagnose, treat and mitigate T2D and fragility fractures.

PI_NAMEs: VASHISHTH, DEEPAK  (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Advanced Glycosylation End Products;Affect;Age;Aging;Assessment tool;Biological Assay;Biological Markers;Body Composition;bone;Bone Density;bone fragility;bone loss;Bone Matrix;bone quality;bone toughness;Cadaver;Calcium ion;Charge;Clinical;cohort;Collagen;cortical bone;Diabetes Mellitus;diabetic;Diagnosis;Dominant-Negative Mutation;Etiology;Exhibits;Femur;Fracture;fracture risk;fragility fracture;Glucose;glycation;Glyoxal;Goals;Growth;Health;Health Care Costs;health data;High Fat Diet;high risk;Hip Fractures;Human;Hydroxyapatites;Hyperglycemia;Impairment;In Vitro;in vitro Model;in vivo;Insulin-Like-Growth Factor I Receptor;Length;Link;Lipids;long bone;Measures;mechanical properties;Mechanics;microCT;mineralization;Minerals;MM form creatine kinase;Modification;Molecular;mouse model;Mus;muscle engineering;N(6)-carboxymethyllysine;Natural Products;Non obese;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Obesity;oxidation;Oxidative Stress;Patients;pentosidine;Persons;Post-Translational Protein Processing;Predisposition;Process;promoter;Property;Proteins;Quality of life;Reaction;Ribose;Risk;Roentgen Rays;Role;Serum;skeletal;Skin;Specimen;spine bone structure;substantia spongiosa;sugar;Techniques;Testing;Time;Tissues;tool;Type 2 diabetic;Urine

PROJECT_TITLE: Effects of Advanced Glycation Endproducts on Type 2 Diabetic and Fragility Fractures

STUDY_SECTION: SBSR

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


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Data Science;Drug Abuse (NIDA only);Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Opioid Misuse and Addiction;Opioids;Pain Research;Substance Misuse

ORG_CITY: Nashville

ORG_DEPT: CHEMISTRY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE Small molecules that selectively activate targeted signaling pathways of the μ-opioid receptor (MOR), such as biased/partial agonists and/or chemogenetic probes, can help to disentangle the mechanisms of analgesia versus dangerous side-effects involved in opioid addiction, as well as potentially act as novel pain management drugs without addictive properties. Here, we will develop computer-aided drug discovery tools that can model large-scale induced-fit conformational changes during drug design and simulate chemogenetics design (receptor-ligand co-design), which we will then apply to identify partial and biased agonists of the MOR and MOR-based DREADDs. In silico molecules and DREADD designs will be experimentally validated and enter hit- to-lead optimization.

PI_NAMEs: BROWN, BENJAMIN PATRICK (contact)

PROGRAM_OFFICER_NAME: ANANTHAN, SUBRAMANIAM

PROJECT_TERMS: Absence of pain sensation;Acute;Adopted;Adult;Agonist;Algorithms;Analgesics;Back;Cessation of life;Chronic;Clinical;Clinical Management;Collaborations;computational platform;Computer Assisted;Dangerousness;deep learning;design;designer receptors exclusively activated by designer drugs;Docking;Drug Design;drug discovery;Feedback;G-Protein-Coupled Receptors;Genetic;in silico;innovation;interest;lead optimization;Ligands;Methods;Modeling;Molecular Conformation;mu opioid receptors;novel;Opiate Addiction;Opioid Receptor;opioid therapy;opioid use disorder;Pain management;Pharmaceutical Preparations;plasma protein Z;Play;prescription opioid;Property;protein structure prediction;Proteins;Rapid screening;receptor;recruit;Resources;Role;side effect;Signal Pathway;Signal Transduction;Signaling Protein;small molecule;small molecule libraries;Structure;targeted treatment;Therapeutic;therapeutic opioid;Time;tool;Ventilatory Depression

PROJECT_TITLE: Developing a computational platform for induced-fit and chemogenetic drug design


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Narrative JC virus (JCPyV) infects greater than 50% of the human population worldwide and causes a fatal central nervous system disease in humans known as Progressive Multifocal Leukoencephalopathy or PML in individuals with compromised immune systems. This proposal focuses on understanding the pathophysiology of JC virus induced PML. Our work is focused on translating our significant work on the basic biology of JCPyV infection to the clinic by the identification of biomarkers and the identification of small compounds that can prevent or treat disease.

PI_NAMEs: ATWOOD, WALTER J (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Anatomy;Autoimmune Diseases;Biology;biomarker identification;Bone Marrow;Brain;Brain Diseases;brain parenchyma;Cells;Central Nervous System;Central Nervous System Diseases;Chronic small plaque psoriasis;Clinic;Complication;Crohn's disease;Development;Disease;extracellular vesicles;Functional disorder;Hematologic Neoplasms;Human;Immune system;Immunologic Surveillance;Immunotherapy;Individual;Infection;Invaded;JC Virus;Kidney;Life;Lytic Phase;macroglia;Mediating;Meningeal;MicroRNAs;Multiple Sclerosis;novel strategies;Patients;Play;Polyomavirus;Population;prevent;programs;Progressive Multifocal Leukoencephalopathy;promoter;receptor;Regulation;Rheumatoid Arthritis;Role;Structure of choroid plexus;Systemic Lupus Erythematosus;Translating;Viral;Virus;Vision;Work

PROJECT_TITLE: Progressive Multifocal Leukoenephalopathy: Endemic Viruses and Lethal Brain Disease


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biotechnology;Chronic Pain;Neurodegenerative;Neurosciences;Pain Research;Pediatric;Peripheral Neuropathy;Rare Diseases

ORG_CITY: MILWAUKEE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Project Narrative: Fabry disease is a lysosomal storage disease whereby lipids collect abnormally inside cells thus disrupting physiological functions. Here we will use a novel animal model of Fabry disease to determine how sensory neurons contribute to the neuropathic-like pain in Fabry disease, ultimately identifying improved pain treatment strategies.

PI_NAMEs: STUCKY, CHERYL LOUISE (contact)

PROGRAM_OFFICER_NAME: GREENWELL, THOMAS

PROJECT_TERMS: 3-Dimensional;Affect;Affective;Afferent Neurons;Age;allodynia;Alpha-galactosidase;Analgesics;Anatomy;Animal Model;Anxiety;Automobile Driving;Behavior;Behavioral;Behavioral Assay;behavioral response;behavioral sensitization;Biology;Categories;Cells;Cellular Morphology;Chronic;conditioned place preference;Consumption;CRISPR/Cas technology;Cutaneous;debilitating symptom;Diameter;Disease;enzyme replacement therapy;Enzymes;Exercise;Exhibits;Fabry Disease;Fatigue;FDA approved;Female;Fever;Fiber;Functional disorder;Gene Deletion;gene replacement;Generations;globotriaosylceramide;Glycosphingolipids;Goals;hearing impairment;Human;Hypersensitivity;Immune response;improved;in vivo;Incidence;Infusion procedures;Intravenous infusion procedures;Ion Channel;knock-down;Lipid Inclusion;Lipids;Lysosomal Storage Diseases;Lysosomes;Maintenance;male;Marble;mechanical stimulus;Mechanics;mechanotransduction;Mediating;Mental Depression;Modeling;Molecular;mustard oil;neuronal cell body;Neurons;Neuropathy;novel;Pain;pain behavior;Pain management;Patients;Peripheral;Persistent pain;pharmacologic;Phenotype;Physiological;Piezo 2 ion channel;Rat Transgene;Rattus;Recombinants;release factor;response;Risk;Role;Running;Schwann Cells;Sensory;Serum;Site;small hairpin RNA;somatosensory;Spinal Ganglia;spontaneous pain;Stimulus;Stress;Swimming;System;Tactile;Testing;Therapeutic Intervention;Time;treatment strategy;TRPA channel

PROJECT_TITLE: Pain Mechanisms in Fabry Disease


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_DEPT: SURGERY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Oral potentially malignant disorders (OPMD) are a common and heterogeneous group of mucosal lesions in the oral cavity without robust and consistent biomarkers for their risk of progression to can cer. Here we propose to use whole slide imaging analysis of routine clinical samples to develop a more robust risk assessment process. These analyses will be combined with genomic and immune biomarkers that should provide improved clinical risk assessment as well as new insights on the biology of progression in OPMD.

PI_NAMEs: PICKERING, CURTIS  (contact);XIAO, GUANGHUA

PROGRAM_OFFICER_NAME: OKI, NOFFISAT

PROJECT_TERMS: Affect;Algorithmic Analysis;Algorithms;Architecture;Biological;Biological Markers;Biology;Biopsy;cancer diagnosis;cancer risk;Case/Control Studies;Cell Nucleus;cell type;Cells;Characteristics;Classification;Clinical;clinical care;Clinical Data;clinical risk;Clinical Trials;cohort;Collection;Computational algorithm;Computer Analysis;Computing Methodologies;Data;data integration;deep learning;Development;Diagnosis;Disease;disorder risk;Dysplasia;Epithelial Cells;Evaluation;Exclusion;Future;General Population;genomic biomarker;genomic data;Genomics;Goals;Hematoxylin and Eosin Staining Method;Heterogeneity;high risk;Histologic;Histology;Histopathologic Grade;Image;Image Analysis;imaging biomarker;Immune;Immunologic Markers;improved;Individual;innovation;insight;Intraepithelial Neoplasia;learning algorithm;Lesion;Leukoplakia;Machine Learning;Malignant - descriptor;malignant mouth neoplasm;Malignant Neoplasms;Measurement;Measures;Methods;Modeling;Morphology;mouth squamous cell carcinoma;Mucous Membrane;mutational status;novel;Oral;Oral cavity;Oral Leukoplakia;Oral mucous membrane structure;oral plaque;Pathologic;Pathology;Patient Care;Patient risk;Patients;Performance;Persons;phenotypic data;predict clinical outcome;predictive modeling;Prevention;Procedures;Process;Process Assessment;Prognostic Marker;prognostic value;progression risk;prospective;Protocols documentation;Recording of previous events;Research;Risk;Risk Assessment;Risk Marker;risk stratification;Sampling;Slide;Stains;Standardization;Statistical Models;System;Testing;Therapeutic Intervention;Tissue imaging;Tissue Sample;Tissues;TP53 gene;treatment planning;Uncertainty;Validation;whole slide imaging

PROJECT_TITLE: Deep Learning Image Analysis Algorithms to Improve Oral Cancer Risk Assessment for Oral Potentially Malignant Disorders

STUDY_SECTION: EITA

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


NIH_SPENDING_CATS: Aging;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_DEPT: ORTHOPEDICS

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Adult stem cells perform tissue maintenance and repair throughout our lifetime but a decline in stem cell function with age leads to progressive and systemic degeneration. There are still significant gaps in our understanding of how aging influences skeletal stem cells. In this proposal, we will determine the molecular mechanisms that regulate skeletal stem cell function and investigate 2 potential therapeutic targets for improved bone healing in the elderly patient.

PI_NAMEs: LEUCHT, PHILIPP  (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Adenosine;Adult;adult stem cell;Affect;Age;age related;age-related disease;aged;Aging;aging population;Agonist;animal old age;Anti-Inflammatory Agents;Apoptosis;Automobile Driving;Biological Assay;bone;bone fracture repair;bone healing;bone health;bone preservation;Bone Regeneration;bone repair;Cell Aging;Cell Count;Cell Physiology;cell type;Cells;Chronic;Data;Deterioration;Down-Regulation;Elderly;Elements;Environment;Enzymes;Equilibrium;experimental study;extracellular;factor A;Feedback;Fracture;fracture risk;Functional disorder;functional loss;gain of function;Genetic Transcription;hallmarks of aging;Homeostasis;Impaired cognition;Impairment;improved;In Vitro;in vivo;Individual;Inflammaging;Inflammation;Inflammatory;inflammatory milieu;Inflammatory Response;Injury;insight;knock-down;lipid biosynthesis;loss of function;Maintenance;Mediating;middle age;Molecular;Monitor;mortality risk;Multipotent Stem Cells;Mus;Musculoskeletal;novel;novel therapeutics;old mice;older patient;Organ;Osteogenesis;osteogenic;overexpression;Pathway Analysis;Pathway interactions;Population;prevent;progenitor;Proliferating;Publishing;Quality of life;receptor;Receptors, Tumor Necrosis Factor, Type II;Regenerative capacity;repaired;Resolution;response;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;skeletal;skeletal stem cell;Skeleton;Small Interfering RNA;stem;stem cell aging;stem cell function;stem cell niche;stem cell self renewal;stem cells;Structure;therapeutic target;Time;Tissues;TNF gene;TNFRSF1A gene;TNFRSF1B gene;transcriptome sequencing;Work

PROJECT_TITLE: Dissecting the aging skeletal stem cell niche

STUDY_SECTION: SBDD

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: KNOXVILLE

ORG_NAME: UNIVERSITY OF TENNESSEE KNOXVILLE

PHR: PROJECT NARRATIVE Membrane proteins are fundamental for the function of the cell. When membrane proteins malfunction, diseases such as cancer occur. We propose to develop a method that allows to study how membrane proteins work, and to design molecules that can be used to prevent errors in the activity of membrane protein.

PI_NAMEs: BARRERA, FRANCISCO NICOLAS (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Acidity;Autoimmune Diseases;Binding;Cell Physiology;Data;design;Development;Disease;Generations;improved;Investigation;Knowledge;Ligand Binding;Ligands;Lipids;Malignant Neoplasms;Membrane;membrane activity;Membrane Proteins;Methods;Molecular;novel therapeutic intervention;Peptides;prevent;receptor;receptor function;single molecule;Stimulus;Thermodynamics;Tissues;Transmembrane Domain;Work

PROJECT_TITLE: Mechanisms of modulation of transmembrane interactions

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


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Contraception/Reproduction;Estrogen;Menopause;Neurosciences;Sleep Research;Social Determinants of Health;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative Menopausal symptoms can impact women's quality of life during the menopausal transition and in old age. Limited evidence exists on the associations between climate-related factors and menopausal symptoms. The proposed research will shed light on the associations of ambient temperature and greenness with menopausal symptoms and sleep duration and quality in women undergoing the menopausal transition.

PI_NAMEs: JOFFE, HADINE  (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Behavioral;Biological;Climate;cohort;Data;Demographic Factors;Epidemiologist;experience;Exposure to;Frequencies;Goals;Green space;Health;Hot flushes;human old age (65+);Longitudinal Studies;Menopausal Symptom;Menopause;Mentors;Mentorship;mullerian-inhibiting hormone;neuroregulation;Outcome;ovarian reserve;parent grant;Perimenopause;Positioning Attribute;psychologic;Quality of life;reproductive;reproductive epidemiology;reproductive senescence;Research;Research Personnel;Severities;skills;Sleep;sleep difficulty;Stress;Symptoms;Temperature;Training;Woman;Women's Health

PROJECT_TITLE: Center for Stress and Neural Regulation of Reproductive Aging Health Outcomes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(70)-R]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: DAVIS

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The proposed research focuses on understanding how plants regulate the strength, duration and specificity of immune responses. Due to significant similarity in immune perception between plants and vertebrates, we anticipate experimental insights will broadly enhance our understanding of immune perception and signaling.

PI_NAMEs: COAKER, GITTA LAUREL (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Animals;Binding;Cells;Cysteine;Data;defense response;Exhibits;Germ Lines;Immune;Immune response;Immune signaling;Immunologic Receptors;Innate Immune Response;Innate Immune System;insight;Leucine-Rich Repeat;Mediating;next generation;Nucleotides;Organ;pathogen;pathogenic bacteria;Pattern recognition receptor;Perception;Phosphotransferases;Plant Leaves;Plants;Post-Translational Protein Processing;Protein Kinase;receptor;Regulation;Research;response;Role;Scientist;Signal Transduction;Specificity;Surface;Training;Vertebrates

PROJECT_TITLE: Immune Perception of Bacterial Pathogens in Plants


ADMINISTERING_IC: CK

IC_NAME: National Center for Emerging and Zoonotic Infectious Diseases

ORG_CITY: JAKARTA PUSAT

ORG_COUNTRY: INDONESIA

ORG_FIPS: ID

ORG_NAME: ALERTASIA FOUNDATION

PHR: Project Narrative The main objectives of this program are to ensure that a well-trained group of Indonesian researchers have the capacity to detect and characterize pathogens of potential human significance from clinical and environmental samples and to examine archival and prospective samples for the presence of human pathogens using a range of virological and molecular methodologies. This new research proposal is designed to build on programmatic elements that were implemented in the CK15-001 which will conclude 7/31/2020. With infrastructure, trained personnel, and primary equipment in place, we can now proceed to discover, diagnose, and characterize vector-borne and zoonotic pathogens; strategically conduct surveillance to establish the role of these pathogens in presentations of acute febrile illness (AFI); and investigate the transmission dynamics of vector-borne and zoonotic disease agents. By the end of Year 5 of this new cooperative agreement, we anticipate having significantly increased and broadened Indonesia’s capacity for molecular diagnosis of emerging vector-borne diseases. Specifically, we plan to have the ability to routinely carry out deep sequencing of selected AFI specimens, institute metagenomic testing, and establish routine testing for Rickettsia and arboviruses found in neighboring countries. We anticipate testing 1000-1500 samples per year collected from all regions of the country. Additionally, we plan to incorporate testing for several pathogens that cause symptoms similar to vector-borne agents and would be included in any differential diagnosis, including leptospirosis and hantavirus. Additional partners and studies will be incorporated in later years of this agreement (CK20-002) to incorporate areas with distinct ecologies and transmission potential as opportunities are identified and deemed appropriate to the goals of the program.

PI_NAMEs: MYINT, KHIN SAW AYE (contact)

PROJECT_TITLE: CK20-002 - Enabling Rapid and Accurate Identification of Emerging Vector-Borne and Zoonotic Threats in Indonesia


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: CAMBRIDGE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative We will develop new computational methods that learn from millions of examples to design antibodies that can be used to help cure a wide variety of human diseases such as cancer and viral infection. Previous antibody design approaches used a trial and error approach to find antibodies that worked well. In contrast our mathematical methods will directly produce new antibody designs by learning from large-scale experiments that test antibodies for function against disease targets. !

PI_NAMEs: GIFFORD, DAVID K (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Affinity;Animals;Antibodies;Antibody Affinity;Antigens;Architecture;Binding;Biological Assay;Budgets;Classification;cloud based;Cloud Computing;commercialization;Communicable Diseases;Computing Methodologies;computing resources;cost;Data;Data Set;deep learning;design;Disease;DNA Sequence;experimental study;Goals;Human;human disease;Immunize;Immunotherapeutic agent;improved;iterative design;Learning;learning strategy;Machine Learning;machine learning method;machine learning model;Malignant Neoplasms;manufacture;mathematical methods;Methodology;Methods;Modeling;molecular dynamics;Molecular Machines;novel;novel strategies;Oligonucleotides;outcome prediction;Output;Performance;Phage Display;Property;Randomized;receptor;Research;Services;Specific qualifier value;Specificity;Statistical Models;Technology;Test Result;Testing;Therapeutic;Time;Training;training data;Treatment Efficacy;Update;Virus Diseases;Work

PROJECT_TITLE: Deep learning based antibody design using high-throughput affinity testing of synthetic sequences

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Mental Health;Prevention;Social Determinants of Health

PHR: Narrative This project will answer basic questions about how life circumstances in both childhood and adulthood affect epigenetic change and how that change in turn is associated with health after age 50 in three countries with different histories and life circumstances. It will add significantly to our understanding of how social, economic, psychological factors get under the skin.

PI_NAMEs: CRIMMINS, EILEEN M (contact);FAUL, JESSICA

PROGRAM_OFFICER_NAME: BRAUDT, DAVID BRUCE

PROJECT_TERMS: Address;Adult;adverse childhood events;Affect;Age;Aging;aging process;aging related;Base Sequence;Behavioral;Biological;Biological Assay;Buffers;Characteristics;Childhood;Chronic Disease;Chronic stress;cognitive function;Collaborations;Collection;comparative;contextual factors;Country;Data;data harmonization;Data Set;design;Development;Diabetes Mellitus;disability;Disease;DNA Methylation;early onset;Economics;Education;Educational Status;epigenetic clock;epigenetic marker;Epigenetic Process;epigenomics;Ethnic Origin;Event;experience;Exposure to;Family health status;frailty;Funding;Funding Agency;Genome;Grant;Grant Review;hallmarks of aging;Health;Health and Retirement Study;Health behavior;Health Policy;Health Promotion;Heart Diseases;Income;Ireland;late life;Life;Life Cycle Stages;Link;Longitudinal cohort study;Longitudinal Studies;Measures;member;Methylation;Minority Groups;Modification;Molecular;mortality;Northern Ireland;older adult;Outcome;Pattern;Persons;Physical Function;Physiological;Policies;Population;population based;potential biomarker;Poverty;Premature Mortality;psychologic;Psychological Factors;Race;Recording of previous events;Research;research and development;resilience factor;Resources;response;Risk;Role;safety net;Sampling;Skin;social;social adversity;social determinants;social disparities;social factors;Social isolation;Social support;socioeconomics;Speed;Stress;Stroke;Surveys;Trauma;United States;United States National Institutes of Health

PROJECT_TITLE: Social Circumstances and Epigenomics Promoting Health in Three Countries

STUDY_SECTION: SSPA

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Clinical Research;Digestive Diseases;Esophageal Cancer;Genetics;Human Genome;Precision Medicine;Rare Diseases;Stomach Cancer

PHR: The proposed research is relevant to public health since long-term survival rates for patients with tumors of the stomach or esophagus remain stubbornly low despite advances in genomics. This work directly addresses this challenge based on the hypothesis that it is possible to use living patient samples ex vivo on rapid timeframes to refine and validate associations between genotype and therapeutic dependency. Since this approach will enable both basic and translational cancer research it is centrally focused on the NCI’s mission to support research to reduce the morbidity and mortality of difficult-to-treat tumors such as gastroesophageal adenocarcinomas.

PI_NAMEs: BOEHM, JESSE SAMUEL (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Address;Ascites;Basic Cancer Research;Benchmarking;Biopsy;Biopsy Specimen;Biosensor;cancer cell;Cancer Model;Cell Line;Cell Survival;cell type;Cells;Clinical;cohort;Collection;CRISPR/Cas technology;Data;Data Collection;Dependence;Derivation procedure;Development;Disease;Drug Exposure;Esophageal Neoplasms;experience;Experimental Models;Foundations;functional genomics;Future;gastroesophageal adenocarcinoma;gastroesophageal cancer;Genomics;Genotype;Goals;Heterogeneity;Image;imaging approach;imaging modality;improved;innovation;Instruction;Label;light transmission;Liquid substance;Malignant Neoplasms;Maps;Methods;microscopic imaging;Microscopy;Mission;model development;Modeling;Molecular;Monitor;Morbidity - disease rate;mortality;novel;novel strategies;Operative Surgical Procedures;Organoids;Outcome Study;Paracrine Communication;patient response;Patients;Pharmaceutical Preparations;pharmacologic;Physiological;Population;pre-clinical;precision medicine;precision oncology;preservation;pressure;Primary Neoplasm;Public Health;Reagent;Reproducibility;Research;Research Personnel;Research Support;Resolution;response;Sampling;Sensitivity and Specificity;single-cell RNA sequencing;Stomach Neoplasms;success;Survival Rate;technology development;Testing;Therapeutic;Therapeutic Studies;Time;timeline;Tissues;tool;translational cancer research;tumor;tumor heterogeneity;Visualization;Work

PROJECT_TITLE: Rapid ex vivo biosensor cultures to assess dependencies in gastroesophageal cancer

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


ORG_DEPT: GENETICS

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE  The proposed research program will use computational approaches to advance genomic, biological and clinical understandings of human disease. We propose a series of studies to: i) quantify population-based penetrance of clinical variants; ii) dissect the phenotypic heterogeneity of complex disease; iii) assess the impact of natural selection using the deleterious load on human phenotypes; and iv) use human genomics to guide drug side effect prediction. Findings from these studies can lead to new biological insights and useful tools that can inform prevention, diagnosis and treatment of human diseases.

PI_NAMEs: DO, RON  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Address;Area;Award;Biological;Clinical;Clinical Data;clinical risk;Code;Complex;Data;data resource;Data Set;Development;Diagnosis;Disease;disorder risk;drug development;Drug Side Effects;Drug Targeting;Electronic Health Record;Evaluation;exome;exome sequencing;fitness;Genes;Genetic;genetic architecture;genetic variant;Genomics;Heterogeneity;Human;human disease;human genomics;improved;indexing;Individual;insight;Knowledge;Laboratories;Link;Medical;Mendelian randomization;method development;National Institute of General Medical Sciences;Natural Selections;novel;Penetrance;Pharmaceutical Preparations;Phenotype;population based;Prevention;programs;Publishing;Research;Research Design;Research Personnel;Risk Factors;Science;Series;Statistical Methods;therapeutic candidate;tool;trait;Translating;translational medicine;Variant

PROJECT_TITLE: Computational approaches to advance genomic, biological and clinical understandings of human disease

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Immunotherapy;Skin Cancer

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Although remarkable progress has been made on a scientific level in understanding regulatory processes governing the activity of the immune system against cancer, the clinical application of these findings to develop effective cancer therapies requires a more detailed knowledge of the molecules and pathways involved. Despite recent advances in anti-PD-(L)1 therapies in over a dozen different cancer types, treatment resistance remains a major unsolved clinical problem. Our objectives are 1) to characterize intratumoral factors, including immune cell, tumor cell, and stromal components, underlying anti-PD-(L)1 resistance; and 2) to use this knowledge to develop more effective cancer immunotherapies based on PD-1 pathway blockade, by co-targeting additional tumor immune resistance pathways.

PI_NAMEs: PARDOLL, DREW M. (contact);TAUBE, JANIS M.;TOPALIAN, SUZANNE LOUISE

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: activin A;Activin Receptor;Address;Advanced Malignant Neoplasm;Affect;Aftercare;anti-PD-1;anti-PD-L1;anti-PD1 therapy;anti-tumor immune response;Antibodies;antitumor effect;Area;Biological Markers;biomarker identification;Biopsy;Blocking Antibodies;cancer immunotherapy;Cancer Patient;cancer therapy;cancer type;cell type;Cells;chemokine;Clinic;Clinical;clinical application;clinical translation;combinatorial;Combined Modality Therapy;Complex;Core Biopsy;Cross Reactions;cytokine;Data;data curation;Development;Dimensions;Dinoprostone;Disease;Dissociation;Elements;Enhancers;Excision;Failure;FDA approved;Formalin;Funding;Gene Expression Profiling;Geography;Head and Neck Squamous Cell Carcinoma;Human;Image;imaging platform;Immune;immune resistance;Immune system;Immunofluorescence Immunologic;Immunohistochemistry;Immunosuppression;Immunotherapeutic agent;Immunotherapy;In Situ;In Vitro;in vivo;in vivo evaluation;in vivo Model;individual patient;inhibitor;Interferon Type II;Knock-in Mouse;Knock-out;Knowledge;Laboratories;Lasers;Ligands;LRRC32 gene;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Melanoma;Membrane;Merkel cell carcinoma;Modeling;Molecular;Monoclonal Antibodies;mouse model;Mus;Nature;Neoadjuvant Therapy;neoplastic cell;next generation;novel;Operative Surgical Procedures;Outcome;Paraffin Embedding;Pathologic;Pathway interactions;Patients;Pattern;PD-1 pathway;PD-1/PD-L1;PDL1 pathway;personalized immunotherapy;Pharmaceutical Preparations;Play;Population;pre-clinical;Process;programmed cell death ligand 1;programmed cell death protein 1;promoter;Prostaglandin Receptor;Prostaglandins;PTGS2 gene;receptor;Regimen;Regulation;Regulatory Pathway;Regulatory T-Lymphocyte;Relapse;Resistance;resistance mechanism;Resolution;responders and non-responders;response;RNA;Role;selective expression;Signal Pathway;Signal Transduction;single-cell RNA sequencing;small molecule;Solid Neoplasm;Sorting;Specimen;spectrograph;Squamous cell carcinoma;standard of care;Structure;T-Lymphocyte;Technology;Testing;therapy resistant;Tissue imaging;Tissue Stains;Tissues;transcriptome sequencing;Transforming Growth Factor beta;Translating;treatment response;tumor;tumor growth;tumor initiation;tumor microenvironment;tumor-immune system interactions;Tumor-infiltrating immune cells;Up-Regulation

PROJECT_TITLE: PD-1/PD-L1 modulation in cancer therapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Hematology;Nutrition

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative Iron is an important factor for hemoglobin synthesis in red blood cells. An insufficient supply of iron is associated with anemia. This proposal seeks to understand the molecular basis of how hemoglobin synthesis is regulated by a mitochondrial protein-dependent signaling in iron-deficient red blood cells.

PI_NAMEs: SEKINE, SHIORI  (contact);SEKINE, YUSUKE

PROGRAM_OFFICER_NAME: ROY, CINDY

PROJECT_TERMS: Address;Anemia;attenuation;Binding;Binding Proteins;Biological;biological adaptation to stress;Cell Death;Cell Line;Cell model;Cell Physiology;Cells;Cessation of life;Characteristics;cofactor;Communication;Cytosol;Data;Death Domain;Defect;Disease;Enhancers;Equilibrium;Erythrocytes;Erythroid;Erythroid Cells;erythroid differentiation;erythroleukemic cell;Erythropoiesis;Exhibits;Globin;Goals;Heme;heme 1;heme a;Hemoglobin;Hemoglobinopathies;Homeostasis;Human;In Vitro;in vivo;Inherited;inhibitor;insight;Iron;iron deficiency;Iron deficiency anemia;iron metabolism;Iron Regulatory Protein 1;Knockout Mice;Life;Lung;Mammals;Mass Spectrum Analysis;Mediating;Messenger RNA;Mitochondria;Mitochondrial Matrix;Mitochondrial Proteins;Modeling;Molecular;Molecular Biology Techniques;Monitor;Mus;novel;novel therapeutic intervention;Organelles;Organism;Outer Mitochondrial Membrane;Oxygen;Pathway interactions;Peptide Hydrolases;Phenocopy;Phenotype;Phosphotransferases;Play;Porphyrins;progenitor;Protein Import;Proteins;Proteomics;proteostasis;Regulation;Reporting;Research Proposals;response;Role;Signal Transduction;Signaling Molecule;Stress;success;Sulfur;System;Testing;therapeutic target;transcription factor;Transcriptional Activation;Transition Elements;Translations;Work

PROJECT_TITLE: Deciphering a Novel Mechanism for Iron-sensing at Mitochondria and Its Role in Erythropoiesis

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: SAN ANTONIO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE Precise regulation of the DNA repair machinery is essential to protect our genetic material from DNA damage and prevent genome instability, which is a hallmark of cancer. Therefore, understanding the regulations how cells control the choice of DNA repair pathway is essential for devising a therapeutic strategy for cancer treatment. Our goal is to elucidate the molecular mechanism on the cell cycle- regulated DNA repair by identifying a key histone mark reader that potentially regulates repair proteins homeostasis at damaged chromatin.

PI_NAMEs: LEUNG, JUSTIN WAI CHUNG (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: BARD1 gene;Binding;Binding Proteins;Biochemical;Biological;Biological Assay;biomarker discovery;BRCA1 gene;cancer cell;cancer therapy;Cell Cycle;Cell Cycle Regulation;Cell Line;Cell Physiology;Cells;Choices and Control;Chromatin;chromatin modification;Complex;Cytoprotection;Defect;Development;DNA;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Repair Gene;DNA Repair Pathway;Docking;Double Strand Break Repair;drug discovery;Drug Targeting;Ensure;Epigenetic Process;epigenome;G1 Phase;Genetic;Genetic Materials;Genetic study;Genome;genome integrity;Genomic Instability;Goals;histone modification;Histones;homologous recombination;Inherited;innovation;insight;Kinetics;Knock-out;Knowledge;Maintenance;Malignant - descriptor;Malignant Neoplasms;Mediating;Mental Retardation;Methylation;Modeling;Molecular;Mutagens;Mutation;neoplastic cell;Nonhomologous DNA End Joining;novel therapeutic intervention;p53-binding protein 1;Pathway interactions;Peptides;potential biomarker;prevent;protective pathway;Proteins;Proteomics;proteostasis;Radiation;Radiation therapy;Reader;Recombinants;recombinational repair;recruit;Regulation;repaired;Reporter;response;Role;Scaffolding Protein;Shapes;Site;spatiotemporal;Tail;Testing;Therapeutic;Therapeutic Agents;Time;Translating;tumor;Work;Zinc Fingers

PROJECT_TITLE: Mechanistic characterization of the cell cycle-dependent DNA repair pathway- Resubmission

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: OMAHA

ORG_NAME: OMAHA VA  MEDICAL CENTER

ORG_STATE: NE

PHR: Peripheral artery disease (PAD) is a cardiovascular disease manifesting from atherosclerotic blockages in the leg arteries which results in physical activity induced claudication, leg pain, discomfort, or cramping. PAD is the most common disorder treated within the surgical service at the Omaha Veterans Affairs Medical Center (VAMC). As the median age of VA patients increases, the number of patients suffering from PAD is expected to rise. PAD results in inability of the ankle plantarflexors to generate normal torque and power in legs. We are currently testing whether ankle foot orthoses can offset ankle plantarflexor torque and power deficiency. The current proposed exoskeleton footwear was developed to address limitations identified in our ongoing trial. Determining the levels of EF assistance force that produce better walking performance and subject-reported preference can improve EF intervention efficacy and prescriptive specifications. The project will provide fundamental information for future implementation and clinical trials in Veterans with PAD.

PI_NAMEs: MYERS, SARA A (contact);PIPINOS, IRAKLIS ILIAS

PROJECT_TERMS: 3-Dimensional;Activities of Daily Living;Address;Adopted;Adoption;Affect;Age;analog;Angioplasty;Ankle;Arteries;Atherosclerosis;Benefits and Risks;Biological;Biomechanics;Blood flow;Bypass;Cardiovascular Diseases;claudication;Clinical Trials;Communities;comorbidity;Compensation;cost;design;Devices;Disease;Distal;Elasticity;Ensure;Exertion;exoskeleton;Fatigue;Fibrosis;Flexor;foot;future implementation;Gait;Goals;Impairment;implementation trial;improved;Individual;Injury;Intervention;Interview;Iowa;Ischemia;Knowledge;Laboratories;Leg;light weight;Lower Extremity;male;Measures;mechanical force;Medical center;Metabolic;Modeling;Morphology;Muscle;Muscle Cramp;muscle physiology;Myopathy;Near-Infrared Spectroscopy;Nebraska;older adult;Older Population;Orthotic Devices;Oxygen;Pain;Pain in lower limb;Participant;patient population;Patients;Pattern;Performance;Peripheral arterial disease;Phase;Physical activity;Population;preference;Procedures;Quality of life;Questionnaires;recruit;Reporting;Research;revascularization;Risk;satisfaction;sedentary;Self-Help Devices;Severity of illness;Shapes;Specific qualifier value;Stress;surgical service;Surveys;Testing;Torque;treadmill;Treadmill Tests;Treatment Efficacy;United States Department of Veterans Affairs;Veterans;Visual;Walking;walking performance;Work

PROJECT_TITLE: Exoskeleton footwear to improve walking performance and subject-reported preference.

STUDY_SECTION_NAME: Rehabilitation Engineering & Prosthetics/Orthotics [RRD5]


NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Networking and Information Technology R&D (NITRD);Nutrition;Obesity;Physical Activity;Prevention;Rural Health;Social Determinants of Health;Telehealth

ORG_CITY: LEXINGTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE  Rural residents, especially Appalachians, have among the nation’s highest rates of cardiovascular disease (CVD), diabetes, and obesity, all associated with unhealthy diet and lack of physical activity. New tools, including personal technology, offers an opportunity to make long lasting behavioral changes and improve health. We will test a culturally adapted evidence-based multicomponent mHealth intervention, Make Better Choices 2 (MBC2), a behavioral program consisting of personalized health coaching, an app, accelerometer, and financial incentives and, explore optimal implementation and sustainment approaches.

PI_NAMEs: PHILLIPS, SIOBHAN MARIE;SCHOENBERG, NANCY E. (contact)

PROGRAM_OFFICER_NAME: BROWN, ALISON GWENDOLYN MARY

PROJECT_TERMS: Acceleration;Accelerometer;acceptability and feasibility;Accountability;active control;active lifestyle;Adaptation research;Address;Adult;Appalachian Region;arm;attentional control;Behavior;behavior change;Behavioral;Blood Pressure;Body mass index;Budgets;Cardiovascular Diseases;cardiovascular disorder risk;Cellular Phone;Characteristics;Chronic;Chronic Disease;Clinical;Communities;Consolidated Framework for Implementation Research;Consumption;contextual factors;cost;Data;design;Devices;Diabetes Mellitus;Diet;Effectiveness;effectiveness evaluation;effectiveness research;effectiveness study;effectiveness testing;effectiveness trial;effectiveness/implementation study;effectiveness/implementation trial;Elements;Equipment and supply inventories;evidence base;Evidence based intervention;experience;Fatty acid glycerol esters;financial incentive;Focus Groups;fruits and vegetables;Future;Goals;good diet;Health;health equity;health inequalities;hybrid type 1 design;implementation context;implementation evaluation;implementation outcomes;implementation research;implementation science;implementation study;improved;Influentials;informant;information gathering;insight;Intake;Internet;Intervention;intervention cost;intervention delivery;intervention program;Interview;iterative design;knowledge base;Leisures;Life Style;Lipids;low socioeconomic status;Malignant Neoplasms;meetings;Methods;mHealth;mhealth interventions;Modality;Monitor;Morbidity - disease rate;mortality;Obesity;Outcome;Participant;Physical activity;physical inactivity;poor health outcome;Population;prevent;primary outcome;Process;programs;Public Health;Randomized;Randomized, Controlled Trials;Recommendation;Reporting;Research Activity;Resources;Rural;Rural Appalachia;rural dwellers;Rural Population;rural underserved;scale up;secondary outcome;sedentary;sedentary lifestyle;Shapes;smartphone application;smartphone based device;stress management;successful intervention;Techniques;Technology;Testing;Time;tool;Training Support;tv watching;Underserved Population;Unhealthy Diet;Uninsured Medical Expense;usability;virtual;Vulnerable Populations;waist circumference

PROJECT_TITLE: Implementing an evidence-based mHealth diet and activity intervention: Make Better Choices 2 for rural Appalachians

STUDY_SECTION: DIRH

STUDY_SECTION_NAME: Dissemination and Implementation Research in Health Study Section[DIRH]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Orphan Drug;Rare Diseases

ORG_CITY: ITHACA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: CORNELL UNIVERSITY

PHR: The emerging henipaviruses are a growing genus of viruses that include the Nipah and Hendra viruses, which are deadly to humans. This study focuses on the viral glycoproteins, which coordinate their efforts to mediate entry of these viruses into host cells, and cell-cell fusion, a pathogenic event in viral infections. Our studies will provide a fundamental understanding of viral entry and cell-cell fusion and identify viral targets for the development of anti-viral therapeutic agents.

PI_NAMEs: AGUILAR-CARRENO, HECTOR  (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Animals;antiviral drug development;Avidity;Biological Assay;Category C pathogen;Cell fusion;Cell Physiology;Cells;Death Rate;Development;Event;Family;Funding;future pandemic;Giant Cells;Glycoproteins;Grant;Head;Hendra;Hendra Virus;Henipavirus;Human;human pathogen;In Situ;Individual;Infection;Knowledge;Link;Maps;Measles;Measures;Mediating;Membrane Fusion;Methods;Modeling;Molecular Conformation;Mumps;mutant;National Institute of Allergy and Infectious Disease;Nature;Nipah Virus;novel;novel strategies;Parainfluenza;Paramyxovirus;particle;pathogen;Pathogenicity;Pathologic;Phenotype;Population;Process;Reagent;receptor;receptor binding;Receptor Cell;Research;research and development;Role;Signal Transduction;Structure;targeted treatment;Testing;Therapeutic;Therapeutic Agents;therapeutic development;therapy development;Time;tool;transmission process;Vaccines;Viral;Viral Proteins;Virus;Virus Diseases

PROJECT_TITLE: Mechanisms of Nipah virus fusion and entry

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


ADMINISTERING_IC: HD

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

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

NIH_SPENDING_CATS: Pediatric

ORG_NAME: MIRIAM HOSPITAL

PHR: PROJECT NARRATIVE Childhood stress and trauma are pernicious public health problems linked to increased risk for an enormous array of behavioral and psychiatric disorders and chronic medical conditions across the lifespan. However, progress toward prevention and intervention to reduce the toll of childhood stress and trauma and promote resilience is limited by the small number of researchers trained to conduct translational, developmentally- informed research focused on mechanisms and health consequences of childhood stress and trauma. Training a cohort of diverse researchers to conduct cutting-edge, rigorous research in childhood stress, trauma and resilience is critical to improve childhood health and prevent disease.

PI_NAMEs: PARADE, STEPHANIE HART;STROUD, LAURA R (contact);TYRKA, AUDREY

PROGRAM_OFFICER_NAME: MAHOLMES, VALERIE

PROJECT_TITLE: Research Training in Childhood Stress, Trauma, and Resilience


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: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Although repeated exposure to stress has been known to impede higher level cognition, including decision- making, our understanding of how stress affects brain regions associated with these functions remains incomplete. Here, we propose a multi-level approach to comprehensively link the behavioral, circuit and cellular level consequences of stress. Our research will yield a mechanistic understanding of how stress influences cognitive function and likely contribute to the future development of intervention strategies.

PI_NAMEs: LUR, GYORGY  (contact)

PROGRAM_OFFICER_NAME: ROSSI, ANDREW F

PROJECT_TERMS: Action Potentials;Acute;Address;Affect;Anterior;Area;area striata;Attention;Auditory;Axon;Behavior;behavior test;Behavioral;Blindness;Brain;Brain region;Calcium;Cells;Characteristics;Chronic stress;cingulate cortex;Cognition;cognitive function;cognitive performance;Color;Data;Decision Making;design;designer receptors exclusively activated by designer drugs;Development;disability;Discrimination;Disease;Economics;Elements;Environment;Excitatory Synapse;experimental study;Exposure to;Functional disorder;Future;Genetic;Guidelines;Health Care Costs;Human;Image;Impaired cognition;Impairment;in vivo calcium imaging;in vivo two-photon imaging;innovation;insight;Intervention;Knowledge;Life Expectancy;Link;Measures;Mediating;Memory;Mental Health;Modality;multimodality;Mus;National Institute of Mental Health;Neocortex;Neurons;neuropsychiatric disorder;novel;novel strategies;operation;optogenetics;outcome prediction;Output;Parietal;Parietal Lobe;patch clamp;Physical Restraint;Play;Poverty;Predisposition;preservation;Prevention strategy;Productivity;Publishing;Pyramidal Cells;Research;response;Risk;Role;Sensory;sensory discrimination;sensory input;sensory integration;Signal Detection Analysis;Slice;Stimulus;Stream;Stress;stressor;Synapses;System;Testing;therapy development;two-photon;Visual;visual stimulus;War

PROJECT_TITLE: Cortical mechanisms of stress-induced cognitive impairment

STUDY_SECTION: PMDA

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


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

PHR: PROJECT NARRATIVE (3 sentences) Pharmaceuticals for treatment of B cell malignancies rely on a class of inhibitors that irreversibly bind the ATP-binding cleft of Bruton's Tyrosine Kinase. Due to their covalent binding within this pocket, these inhibitors have significant off-target side effects and are susceptible to resistance mutations. The goal of this project is to elucidate the lipid-binding and oligomerization of Btk to understand the mechanism of membrane association as potential alternative sites and pathways for Btk inhibition.

PI_NAMEs: MCALLISTER, RACHEL  (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: adaptive immune response;Adaptive Immune System;Agammaglobulinaemia tyrosine kinase;Antibodies;antigen binding;Antigens;B cell differentiation;B lymphocyte immortalization;B lymphoid malignancy;B-Cell Activation;B-Cell Antigen Receptor;B-Lymphocytes;Binding;Binding Sites;Biochemical;Biological Assay;cancer cell;cancer therapy;Cell Line;Cell membrane;Cell Proliferation;chemotherapy;Chronic Lymphocytic Leukemia;Complex;Conserved Sequence;Data;Detection;DNA;Environment;Event;experimental study;Generations;Genetic Transcription;Goals;Immunity;In Vitro;in vivo;Informal Social Control;inhibitor;Learning;Length;leukemia/lymphoma;Lipid Bilayers;Lipid Binding;Lipids;Malignant Neoplasms;Mass Spectrum Analysis;Measures;Membrane;Membrane Proteins;Modeling;Molecular;Molecular Conformation;mutant;Mutation;NF-kappa B;Non-Hodgkin's Lymphoma;novel;nuclear factors of activated T-cells;overexpression;pathogen;Pathway interactions;PH Domain;pharmacologic;Pharmacologic Substance;Phosphatidylinositols;Phosphatidylserine Synthase;Phosphatidylserines;phosphoproteomics;Phosphotransferases;Predisposition;preservation;Proliferating;Protein Tyrosine Kinase;Proteins;Raji Cell;Receptor Activation;Receptor Signaling;recruit;Research;Resistance;resistance mutation;response;Sequence Homology;side effect;Signal Pathway;Signal Transduction;Site;Specificity;stoichiometry;success;Surface;Training;tripolyphosphate;Tyrosine Kinase Inhibitor;United States Food and Drug Administration;Vesicle;Western Blotting

PROJECT_TITLE: Molecular mechanism of membrane association of Bruton's Tyrosine Kinase


NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Genetics

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: Project Narrative Autoimmune, or insulin-dependent diabetes mellitus, is characterized by an inflammatory reaction in and around pancreatic islets, followed by selective destruction of b-cells. Soluble mediators known as cytokines are believed to contribute to b-cell damage during this process. We have recently uncovered a number of protective responses that are activated by cytokines and the long range goals of this work are to identify potential thearputic potential of these b-cell protective pathways in an effort to treat or prevent autoimmune diabetes.

PI_NAMEs: CORBETT, JOHN A (contact)

PROGRAM_OFFICER_NAME: WANG, XUJING

PROJECT_TERMS: aerobic glycolysis;antioxidant enzyme;Antioxidants;Apoptotic;Attenuated;Autoimmune;Autoimmune Diabetes;B-Lymphocytes;Bathing;Beta Cell;Biochemical;Biological;Blood;Blood flow;blood glucose regulation;blood perfusion;Blood Volume;cell injury;Cell Physiology;Cell Respiration;Cell Survival;Cells;Chemicals;Collection;cytokine;Cytoprotection;Data;design;Development;Diabetes Mellitus;DNA Damage;Endocrine;Equilibrium;Exposure to;Fever;flexibility;Gene Expression;Genes;Glucokinase;Glucose;Glucose Transporter;Goals;Hormone secretion;Hormones;Human;Immunologics;Impairment;Incidence;Individual;Infection;Infectious Agent;Inflammation;Inflammation Mediators;Inflammatory;Injury;insight;Insulin;insulin secretion;Insulin-Dependent Diabetes Mellitus;Interferon Type II;Interferons;Interleukin-1;islet;Islets of Langerhans;Knockout Mice;Liver;loss of function;LoxP-flanked allele;Mediating;Mediator;Metabolic;Mitochondria;Molecular;mouse model;Mus;Nitric Oxide;Nitrogen;oxidation;Oxidative Stress;Oxygen;Pancreas;Pathway interactions;peroxiredoxin;Phosphorylation;Physiological;Predisposition;preservation;prevent;Process;Production;programs;protective pathway;Proteins;Rat-1;Reaction;Recurrence;Recurrent disease;Research;response;Role;self-renewal;Signal Transduction;single-cell RNA sequencing;Structure of beta Cell of islet;System;Techniques;Testing;Therapeutic;TNF gene;Toxin;Transgenic Organisms;Translations;Transplantation;Travel;TXN gene;Vascularization;Viral;Viral Genes;Weight;Work

PROJECT_TITLE: Biochemical Mechanism of Beta-Cell Destruction

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


NIH_SPENDING_CATS: Bioengineering;Genetics;Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Umbilical Cord Blood/ Placenta;Stem Cell Research - Umbilical Cord Blood/ Placenta - Human

ORG_CITY: SEATTLE

ORG_NAME: INSTITUTE FOR SYSTEMS BIOLOGY

ORG_STATE: WA

PHR: The proposed research is relevant to public health because understanding the mechanism that controls the formation of functional red blood cells is essential to aid in the design of new therapeutic strategies for anemic patients such as those suffering from ß-thalassemia. Thus, the project is relevant to NIH’s mission to pursue fundamental knowledge and to help reduce the burdens of human illness.

PI_NAMEs: BRAND, MARJORIE CAROLE;PRICE, NATHAN D;RANISH, JEFFREY A (contact)

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: Adult;Anemia;Automobile Driving;Benchmarking;beta Globin;beta Thalassemia;Binding;Blood;Cell Fate Control;Cell model;Cell Physiology;Cell Surface Proteins;Cells;Chromatin;comparative;Complex;Computer Analysis;Data;design;Disease;dosage;Erythrocytes;Erythroid;Erythroid Cells;Erythropoiesis;experimental study;fetal;FLI1 gene;Gene Expression;Genes;Genetic Transcription;genome-wide;Genomics;Goals;Health;Hematopoietic stem cells;Hemoglobin;histone modification;Histones;Human;human model;improved;in vivo;innovation;insight;Joints;Knowledge;Mass Spectrum Analysis;Measurement;Measures;Messenger RNA;Methodology;Methods;Mission;Modeling;Nature;network models;novel;novel therapeutic intervention;novel therapeutics;Outcome;Patients;pharmacologic;Population;Process;Production;progenitor;programs;Proteins;Proteome;Proteomics;Proxy;Public Health;Regulation;Research;Role;Specific qualifier value;stem cells;System;Technology;temporal measurement;Testing;Time;Transcript;transcription factor;transcription regulatory network;Transcriptional Regulation;transcriptome;Umbilical Cord Blood;United States National Institutes of Health;Validation;Work

PROJECT_TITLE: Transcriptional Control During Erythropoiesis

STUDY_SECTION: MCH

STUDY_SECTION_NAME: Molecular and Cellular Hematology Study Section[MCH]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Cannabinoid Research;Clinical Research;Drug Abuse (NIDA only);Substance Misuse

ORG_NAME: BROWN UNIVERSITY

PHR: Public Health Relevance  Project Narrative Driving under the influence of cannabis and related traffic fatalities have become a major public health concern, but little is known about how and when cannabis users decide whether to drive after using cannabis. The project will use mobile technology to assess immediate influences of “real life” contexts in a person’s daily life on the decision to drive after using cannabis. The project will provide information critical to the development of cannabis policy and prevention efforts to reduce the risk of driving under the influence of cannabis.

PI_NAMEs: METRIK, JANE  (contact)

PROGRAM_OFFICER_NAME: GROSSMAN, ELYSE RACHELLE

PROJECT_TERMS: Accelerometer;Acute;Affect;Affective;Area;Automobile Driving;Behavior;Cannabidiol;Cannabinoids;Cannabis;Cannabis policy;Cannabis retail;cannabis use behavior;Cellular Phone;Characteristics;Cognition;contextual factors;Cues;Dangerousness;Data;Decision Making;Destinations;Development;Devices;driving skills;driving under influence;Ecological momentary assessment;Elements;Event;experience;Frequencies;Friends;Geographic Locations;Geography;Impairment;Impulsivity;indexing;Individual;Individual Differences;insight;interest;Interview;Intoxication;Laws;Life;Link;Location;Machine Learning;Maps;marijuana legalization;marijuana use;marijuana user;Measures;Methods;mobile computing;Movement;Near-Infrared Spectroscopy;negative affect;Neighborhoods;Outcome;Participant;Pattern;peer;Perception;permissiveness;Persons;pharmacologic;Policies;Positioning Attribute;Prevention;Process;prospective;Public Health;public health relevance;Reporting;Research;Risk;Risk Factors;Risk Reduction;risky driving;Route;Safety;Science;Short-Term Memory;sobriety;social;Social Environment;spatiotemporal;Speed;substance use;Technology;Testing;Tetrahydrocannabinol;Time;Travel;Weather;Work

PROJECT_TITLE: Individual, contextual, and geospatial influences on decisions to drive under the influence of cannabis

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Maternal Health;Mental Health;Neurosciences;Nutrition;Pediatric;Pregnancy;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: PORTLAND

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Maternal systemic inflammation during pregnancy represents a potential common pathway for effects of a diverse range of preconception and prenatal factors on the developing fetal brain with implications for long term neurodevelopmental outcomes and risk for psychiatric disorders. The current research and training plan addresses major limitations of the research in this area to date by implementing multivariate statistics and cross validation across three independent datasets to capture the complexity of effects of maternal psychosocial, life history and health factors on the maternal inflammatory milieu during pregnancy. Further, heterogeneity in the maternal inflammatory milieu (and specifically cytokine networks) is examined as a mechanism through which variability in prenatal conditions alter offspring neurodevelopment.

PI_NAMEs: ALLEN, MADELEINE  (contact)

PROGRAM_OFFICER_NAME: GIRARDI, GUILLERMINA

PROJECT_TERMS: Address;Affect;Anti-Inflammatory Agents;Area;Awareness;Biological;Biology;Body mass index;Body Size;Brain;Cluster Analysis;Communications Media;Complex;Conceptions;cytokine;Cytokine Network Pathway;Data Set;Decidua Basalis;demographics;Development;dimensional analysis;Dimensions;Discipline of obstetrics;Endocrine;Environment;Experimental Designs;fetal;Goals;Health;Heterogeneity;high dimensionality;Historical Demography;Immune;Individual;Inflammation;Inflammatory;inflammatory milieu;innovation;life history;life span;Literature;longitudinal dataset;Maternal Health;Measures;meetings;Mental disorders;Methods;multidimensional data;Multivariate Analysis;Nature;neurobehavioral;neurodevelopment;Neurosciences Research;nutrition;offspring;Outcome;Participant;Pathway interactions;Pattern;Population;Pregnancy;prenatal;prenatal health;Prenatal Nutrition;prepregnancy;Principal Component Analysis;Psychological Stress;Psychopathology;psychosocial;Psychosocial Factor;Psychosocial Stress;Recording of previous events;Reproducibility;Research;Research Design;response;Risk;Risk Factors;Role;Science;sociodemographics;statistics;Stress;Subgroup;systemic inflammatory response;Techniques;Training;Trauma;United States National Institutes of Health;Validation;Variant;Weight Gain;Work

PROJECT_TITLE: A Multidimensional Approach to Understanding Prenatal Health and Psychosocial Factors in Relation to the Maternal Inflammatory Milieu and Offspring Neurodevelopment

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


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Nutrition;Obesity;Precision Medicine;Prevention

ORG_CITY: PROVIDENCE

PHR: PROJECT NARRATIVE Although dietary lapses (i.e., instances of non-adherence to dietary goals) are a major cause of poor outcomes during behavioral obesity treatment, poorly understood variability in types of lapse behaviors and their mechanisms interferes with an ability to intervene on them. Therefore, we propose to use multimodal real-time assessment of behavioral, psychosocial, and contextual information to uncover and validate lapse phenotypes (i.e., meaningful clusters of lapse behaviors, such as lapsing via overeating vs. lapsing via eating an off-plan food), and then validate these emerging phenotypes by testing their associations with weight change and energy intake. By applying a multi-level analysis approach to phenotype specific lapse behaviors clustered within individuals over time, this project will: a) support the development of sophisticated theoretical models of adherence behaviors, b) inform precision tools that improve dietary adherence in behavioral treatments for obesity, and c) establish novel phenotyping methods that can be used to understand and intervene upon non- adherence across a myriad of other chronic health conditions (e.g., diabetes, renal disease).

PI_NAMEs: GOLDSTEIN, STEPHANIE PAIGE (contact)

PROGRAM_OFFICER_NAME: EVANS, MARY

PROJECT_TERMS: adaptive intervention;Adherence;Adult;Assessment tool;Behavior;Behavior assessment;behavior influence;Behavior Therapy;Behavioral;behavioral phenotyping;Body Weight Changes;Body Weight decreased;Calories;Cellular Phone;Characteristics;Chronic;Clinic Visits;Clinical;clinically significant;Complex;compliance behavior;contextual factors;Data;Data Analyses;Development;Devices;Diabetes Mellitus;Diet;dietary;dietary adherence;Dietary Assessment;disorder risk;Disparate;Eating;Eating Behavior;Ecological momentary assessment;Energy Intake;Environmental Risk Factor;Factor Analysis;Food;Future;Goals;Health;Health behavior;Hour;Hyperphagia;improved;Individual;individual variation;innovation;Intervention;Kidney Diseases;Knowledge;Maintenance;Measurement;Measures;Methods;multilevel analysis;multimodality;novel;Obesity;obesity treatment;Outcome;Overweight;Participant;Patient Self-Report;Patients;Pattern;personalized intervention;Persons;Pharmaceutical Preparations;Phenotype;precision medicine;Predisposition;prevent;Psychological Factors;psychosocial;Psychosocial Factor;Recommendation;Research;Science;Secondary to;Severities;Smoking;Surveys;Techniques;telephone based;Testing;Theoretical model;Time;tool;Treatment Failure;Treatment outcome;Weight;Weight maintenance regimen;Work;Wrist

PROJECT_TITLE: Using Multimodal Real-Time Assessment to Phenotype Dietary Non-Adherence Behaviors that Contribute to Poor Outcomes in Behavioral Obesity Treatment

STUDY_SECTION: BMHO

STUDY_SECTION_NAME: Biobehavioral Medicine and Health Outcomes Study Section[BMHO]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: PROJECT NARRATIVE Depression in the United States is one of the most common psychiatric disorders and can represent a significant cost to quality of life. Findings from the proposed research would enhance knowledge on the effects of neighborhood-level features such as residential segregation and neighborhood social cohesion on depression and the pathways leading to the association in Latino communities. This research would lay the foundation for the development of strengths-based interventions that may be leveraged to improve the mental health of Latinos and other underserved communities and in turn advance mental health equity.

PI_NAMEs: DIAZ, SARAH VALENTINA (contact)

PROGRAM_OFFICER_NAME: AVENILLA, FRANK R

PROJECT_TERMS: Address;Adult;Affect;Ancillary Study;built environment;caucasian American;Characteristics;Communities;cost;Data;Data Analyses;Data Set;Depressed mood;depressive symptoms;Development;Ethnic Population;experience;falls;Fellowship;Foundations;Future;General Population;Geography;Goals;Health;Health behavior;Health Benefit;health equity;health inequalities;Health Surveys;hispanic community;Hispanic Community Health Study/Study of Latinos;implementation research;improved;Individual;insight;interest;Intervention;Intervention Studies;Knowledge;Language;Latino;Latino Population;Latinx;Link;Literature;marginalized community;Measures;Mediation;Mediator;Mental Depression;Mental disorders;Mental Health;Mentorship;Methodology;Methods;Minority Groups;Minority Health Research;Modification;Multi-Ethnic Study of Atherosclerosis;multilevel analysis;National Institute of Mental Health;neighborhood association;Neighborhoods;Not Hispanic or Latino;Pathway interactions;Patient Self-Report;Personal Satisfaction;Persons;Population;population based;Poverty;Quality of life;Race;Reporting;Research;Research Personnel;Research Training;residential segregation;Resources;Respondent;Risk;Running;Sampling;Scientist;segregation;Services;single episode major depressive disorder;skills;social cohesion;social culture;Social Environment;social health determinants;social relationships;Social support;Source;Spanish;Spanish/English;Spatial Distribution;spatial relationship;stress reduction;structural determinants;Study of Latinos;Subgroup;success;Time;Training;Training Programs;Trust;underserved community;United States

PROJECT_TITLE: Neighborhood Social Environment, Composition and Depression in Latinx


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE The nervous system possesses unique immune response aspects that are altered in the context of neurological disorders, ranging from glioblastoma, the most common primary malignant brain tumor, to neuroinflammatory conditions and neurodegenerative disorders. Glioblastoma is highly infiltrated by myeloid-derived suppressor cells (MDSCs) that drive tumor growth and reduce the efficacy of standard therapies, including checkpoint inhibitors. The objectives of this project are to use glioblastoma as a model for neurological disorders to identify the cellular and molecular basis for MDSC lineage commitment and plasticity, interrogate the response of MDSCs to microenvironmental cues, and evaluate pre-clinical MDSC targeting in combination with immune activating therapies.

PI_NAMEs: LATHIA, JUSTIN D. (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Address;Advanced Malignant Neoplasm;Area;Biological Markers;Brain;cancer stem cell;Cell Lineage;Cells;Clinical;Cues;cytotoxic;Development;Disease Progression;Epigenetic Process;flexibility;Funding;Genetic;Glioblastoma;granulocyte;Growth;gut-brain axis;Immune;immune activation;Immune checkpoint inhibitor;Immune response;Immunosuppression;Infiltration;insight;Knowledge;Laboratories;Malignant neoplasm of brain;Mediating;microorganism interaction;Molecular;monocyte;Myeloid-derived suppressor cells;Nervous System;Nervous System Disorder;neural;Neurodegenerative Disorders;Neuroimmune system;neuroinflammation;Neurological Models;novel therapeutics;Patients;pre-clinical;Primary Brain Neoplasms;proctolin;Prognosis;programs;response;Series;sex;Signal Transduction;stem cell function;success;Testing;Therapeutic;therapeutic target;tumor;tumor growth;Work

PROJECT_TITLE: Contribution of Myeloid-Derived Suppressor Cells to Neuro-Inflammatory Alterations and Disease Progression in Glioblastoma


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Cocaine;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: RICHMOND

ORG_DEPT: PSYCHIATRY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Project Narrative Substance use disorders represent a major public health issue, and improved therapies are needed but pre- clinical models of addiction have not translated well into improved therapy options. An improved understanding of the clinical neurobiology of addictions may help refine preclinical models of addiction which may help inform the development of future therapies. The present study aims to further our understanding of the neurobiology of these disorders by assessing between-network functional connectivity and effective connectivity among three key brain networks (Salience Network, Default Mode Network, and Executive Control Network) in opioid and cocaine use disorder subjects compared to non-drug using controls.

PI_NAMEs: WOISARD, KYLE  (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: addiction;Awareness;Brain;Brain Diseases;Brain region;causal model;Clinical;Cocaine use disorder;COVID-19 pandemic;craving;Cues;Data;Development;Disease;Epidemic;executive function;Functional Magnetic Resonance Imaging;Future;Human;improved;insight;interest;Left;Lesion;Measurement;Modeling;Neurobiology;neurophysiology;Neurosciences;non-drug;opioid use;opioid use disorder;Patients;Pattern;Pharmaceutical Preparations;Pharmacotherapy;pre-clinical;Pre-Clinical Model;Prevalence;Public Health;Publishing;Research;Rest;Substance Use Disorder;tool;United States Dept. of Health and Human Services;United States Food and Drug Administration

PROJECT_TITLE: Resting State fMRI Functional and Effective Connectivity in Opioid and Cocaine Use Disorders


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE An effective immune response requires a fine balance between effector T cells that can eliminate pathogens and regulatory T cells that prevent autoimmunity. We hypothesize that a unique population of regulatory T cells recirculate back to the thymus (the site of all T cell development) and act as a rheostat to decrease the stringency of selection once peripheral regulatory T cell tolerance is established, thereby allowing for a more diverse and pathogen-reactive conventional immune system to emerge.

PI_NAMEs: FARRAR, MICHAEL ARCHIBALD (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Adult;Affect;Age;Antigen-Presenting Cells;Antigens;Autoimmunity;autoreactive T cell;autoreactivity;Back;Biological;Cell Count;Cell Density;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;central tolerance;Clonal Deletion;cross reactivity;Cytolysis;Development;Disease;Effector Cell;effector T cell;Ensure;Equilibrium;experimental study;FOXP3 gene;Growth;Heterogeneity;Homeostasis;Human;Immune;Immune response;Immune system;Immune Tolerance;Immunity;Immunologic Surveillance;immunopathology;immunoregulation;Impairment;Infection;Life;Maintenance;Mediating;mouse model;Mus;novel;Organ;Output;pathogen;perforin;Perinatal;Peripheral;Play;Population;prevent;Process;Regulation;Regulatory T-Lymphocyte;Role;Self Tolerance;Site;System;T cell receptor repertoire sequencing;T-Cell Development;T-cell diversity;T-cell receptor repertoire;Testing;Thymic epithelial cell;thymocyte;Thymus Gland;Time;TNFSF10 gene;TNFSF6 gene;transcription factor;transcriptome sequencing;transcriptomics;tumor

PROJECT_TITLE: Regulation of central tolerance and Treg development by recirculating Treg

STUDY_SECTION: TTT

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


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: BOSTON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

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

PHR: Project Narrative Genome-wide association studies (GWAS) have been extremely successful in identifying genetic loci associated with complex diseases. This project aims to develop a statistical method to accurately infer the causal tissue and gene responsible for the functional consequences of each disease locus, thereby furthering our knowledge of disease biology. This project further aims to infer disease subtypes linked to specific tissues using polygenic risk scores, providing a new paradigm for inferring disease subtypes.

PI_NAMEs: STROBER, BENJAMIN  (contact)

PROGRAM_OFFICER_NAME: FUFA, TEMESGEN D

PROJECT_TERMS: Automobile Driving;Biological Assay;biological systems;Biology;Candidate Disease Gene;career;causal variant;Communities;Complex;Computer software;Data;Development;Disease;disease heterogeneity;disorder subtype;Drug Targeting;Evaluation;Gene Expression;Genes;Genetic;Genetic Models;Genetic Risk;genome wide association study;genomic locus;Genotype;Individual;insight;interest;Knowledge;Link;Maps;Mediating;Metabolic;Methods;novel;open source;Patient Care;Pattern;Phenotype;Physiological;polygenic risk score;Postdoctoral Fellow;Probability;Regulation;Research;Research Personnel;skills;Statistical Methods;statistics;Testing;Tissues;Training;trait;transcriptome;Variant;Work

PROJECT_TITLE: Fine-mapping causal tissues at disease-associated loci to infer disease subtypes

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


NIH_SPENDING_CATS: Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE E2 ependymal cells are recently-identified, bi-ciliated cells in the walls of the brain ventricles, located next to adult neural stem cells and brain regions regulating body homeostasis. We propose to characterize E2 cells' specialized cilia, molecular signature, population dynamics, and determine how E2 cell cilia signaling regulates the adult neural stem cell niche.

PI_NAMEs: ALVAREZ-BUYLLA, ARTURO  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Ablation;Address;Adult;adult neurogenesis;adult stem cell;Affect;Age;Aging;alertness;Apical;Apoptosis;Apoptotic;Area;Basal Cell;blood glucose regulation;Brain;brain parenchyma;Brain region;Bromodeoxyuridine;Cell Count;Cell Nucleus;Cell Physiology;Cell Proliferation;cell type;Cells;Central cord canal structure;Cerebral Ventricles;Cerebrospinal Fluid;cerebrospinal fluid flow;Characteristics;Cilia;ciliopathy;cilium motility;Circadian Rhythms;Complex;Conscious;Data;Dependovirus;Detection;Development;Disease;Electrons;Embryo;Ependymal Cell;Ependymoma;Excision;Exhibits;feeding;Floor;Fourth ventricle structure;Functional disorder;Gene Expression;Gene Expression Profiling;Generations;Genetic;Growth;Half-Life;Homeostasis;Human;Hydrocephalus;kinetosome;Knowledge;Label;Laboratories;lateral ventricle;Life;Link;Location;Malignant Neoplasms;Mediating;Metabolic Diseases;Microscopy;migration;Molecular;molecular marker;Molecular Profiling;Motility;mRNA sequencing;Mus;Natural regeneration;nerve stem cell;neuroblast;neurogenesis;Neuroglia;Neurons;novel;Organelles;Pathway interactions;Play;Population;Population Dynamics;postnatal;prevent;Proliferating;promoter;Property;Regenerative capacity;Regulation;Role;Sensory;Signal Pathway;Signal Transduction;Signaling Molecule;Sleep;Speed;stem cell niche;stem cell proliferation;stem cells;Structure;subventricular zone;Testing;Third ventricle structure;Time;transcriptome sequencing;transmission process;ultra high resolution;Ventricular;ventricular system;Work

PROJECT_TITLE: Structure and function of a novel population of regenerating ependymal cells

STUDY_SECTION: CMBG

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


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

ORG_CITY: Princeton

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: Project Narrative: Bacteria have huge positive and negative impacts on human health, and we desperately need new strategies to combat pathogens and shape microbiome composition. We recently found that bacteria don't just affect us through chemicals, but also through their small RNAs (sRNAs). Building off our paradigm-shifting results, here we propose innovative new strategies to identify the sRNAs that “talk” to hosts from pathogens and the healthy microbiome, define how they function, and develop them as candidate immune-modulating therapeutics.

PI_NAMEs: ABOU DONIA, MOHAMED ;GITAI, ZEMER  (contact);MURPHY, COLEEN TARA

PROGRAM_OFFICER_NAME: KIM, HYE-SOOK

PROJECT_TERMS: Address;Affect;Animal Model;Animals;Anti-sense RNA;Antibiotic Resistance;Antibiotics;antimicrobial;Area;Bacteria;Bacterial RNA;bacteriome;Base Sequence;Behavior;Biological Assay;Biological Markers;Biology;Caenorhabditis elegans;Cells;Chemicals;combat;Communities;Computational Biology;Data;design;Development;Disease;Dissection;drug development;Eating;Elements;experience;flexibility;Food;Foundations;Genes;Genetic Transcription;Genome;Genomics;Goals;gut microbiome;Health;Healthcare;High temperature of physical object;host-microbe interactions;Human;Human Microbiome;human pathogen;Immune;immune modulating agents;Immune response;immune system function;Immunomodulators;Infection;innovation;insight;Intervention;Knowledge;Learning;Lung;Mammalian Cell;Mammals;Maps;Mediating;Mediator;member;Microbe;microbial;microbiome;microbiome composition;Modeling;Molecular;novel;novel antibiotic class;novel strategies;novel therapeutics;Nucleic Acids;Nutritional;Organism;pathogen;Pathogenesis;pathogenic bacteria;Patients;Pharmaceutical Preparations;Pharmacology;Probiotics;Pseudomonas aeruginosa;Reading;Research;Research Project Grants;resistance mechanism;Resources;response;Risk;RNA;RNA Interference;RNA Interference Pathway;Role;Shapes;Signal Transduction;Signaling Molecule;small molecule;Small RNA;Societies;Source;Spielmeyer-Vogt Disease;success;Surface;Therapeutic;therapeutic RNA;Virulent;ward;Work

PROJECT_TITLE: Small RNAs as Novel Modulators of Microbe-Host Interactions

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-J(70)R]