ORG_CITY: SCOTTSDALE

ORG_NAME: MAYO CLINIC ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE We have discovered that removal of CD2 increases FOXP3 expression and immunoregulatory functions of regulatory T cells (Tregs). We propose some mechanistic studies to uncover molecules and/or signaling pathways involved in determining the fate of Tregs, targeting of which could alter the immune balance toward tolerance. Also, using a pig-specific chimeric antigen receptor (CAR) that we have developed, we will explore the translational aspects of this discovery in humanized mouse model of xeno-islet transplantation (CD2-KO anti pig CAR Treg therapy).

PI_NAMEs: KHOSRAVI MAHARLOOEI, MOHSEN  (contact)

PROGRAM_OFFICER_NAME: NABAVI, NASRIN N

PROJECT_TERMS: Acetyl Coenzyme A;Acetylation;Address;Adverse effects;Antibodies;Antigens;Autoimmunity;cadmium ion;CD2 Antigens;Cells;Cellular immunotherapy;chimeric antigen receptor;Citrates;Citric Acid Cycle;clinical application;conditioning;Cytosol;Data;Deacetylase;Development;effector T cell;efficacy evaluation;epigenome;Equilibrium;Excision;Family suidae;FOXP3 gene;Genetic Transcription;Genome;Glycolysis;Histone Acetylation;histone modification;HLA Antigens;Human;humanized mouse;Immune;Immune response;Immune system;immunoregulation;Immunosuppression;In Vitro;in vivo;Inflammatory;islet;Islets of Langerhans Transplantation;Link;Mediating;Metabolic;Metabolism;Mitochondria;Modeling;mouse model;NADH;Organ;Organ Transplantation;Pathway interactions;Post-Translational Protein Processing;prevent;Protein Acetylation;Proteins;Regimen;Regulatory T-Lymphocyte;Resistance;Respiration;Signal Pathway;Signal Transduction;Siplizumab;SIRT1 gene;Source;T cell therapy;T-Cell Depletion;T-Lymphocyte;transcriptome;Transplantation;Ubiquitin;Work;Xenograft procedure

PROJECT_TITLE: Delineating mechanisms underlying the enhanced stability and functionality of CD2- KO Tregs and chimeric antigen receptor (CAR) Tregs and their application in xenotransplantation

STUDY_SECTION: TTT

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


ADMINISTERING_IC: EY

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Eye Disease and Disorders of Vision;Neurosciences;Pediatric

ORG_CITY: STANFORD

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OPHTHALMOLOGY

ORG_FIPS: US

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Approximately 3% percent of infants and children 6 to <72 months have strabismus (crossed eyes) or amblyopia (lazy eye). The development of amblyopia and strabismus are the result of abnormal vision development in the first few years after birth. The knowledge we gain about the roles of the sensory and motor visual systems and how they communicate during early vision development, particularly in farsighted infants and young children, will lead to the ability to identify infants at highest risk and thus result in improved patient outcomes.

PI_NAMEs: ROBERTS, TAWNA  (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Adult;Afferent Pathways;Age;Age Months;Amblyopia;Birth;Blindness;Caring;Child;Childhood;Clinical;Clinical Research;clinically significant;Communication;Complex;crosslink;design;Detection;Development;Diplopia;Early Intervention;Efferent Pathways;Elements;emmetropization;Esotropia;Evidence based treatment;experience;Eye;fundamental research;Future;Goals;high risk;Hyperopia;improved;improved outcome;individualized medicine;Infant;Knowledge;Lazy Eyes;Learning;lens;Longitudinal Studies;Measures;Methodology;Modeling;neural;neurophysiology;oculomotor;Outcome;Patient-Focused Outcomes;Phase;Preventive measure;Process;Refractive Errors;response;Retina;retinal imaging;Risk;Role;Sensory;Signal Transduction;Stimulus;Strabismus;System;Targeted Research;Testing;Training;treatment strategy;Vision;vision development;Visual;visual motor;Visual System

PROJECT_TITLE: Afferent and Efferent Visual Systems During Abnormal Vision Development


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: CHICAGO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The proposed study is to develop an ultra-low-input RNase footprinting approach for simultaneous quantification of cytosolic and mitochondrial translation. The method will open up an avenue to examining the transcriptomic translation using primary tissue samples for both basic scientific research and clinical prognosis. We will apply it to study the dynamic regulation of translational control during hematopoiesis and build the functional network mediated by mitochondrial translation factors. Our study will lead to novel insights into physiological roles and molecular mechanisms of translational regulation.

PI_NAMEs: JI, ZHE  (contact)

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: Address;Amino Acids;Biological Assay;Blood;Bone Marrow;cancer cell;Cell Count;Cell Differentiation process;cell growth;cell type;Cells;clinical prognosis;Codon Nucleotides;Complex;Consumption;cost;CRISPR library;CRISPR screen;Cultured Cells;Data;Dependence;design;Development;Digestion;Disease Progression;Freezing;Genes;Genome;genome-wide;Genomics;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Heterogeneity;Hour;human disease;in vivo;Individual;insight;Knock-out;Length;Libraries;Lymphocyte;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Mediating;Methods;Mitochondria;mitochondrial genome;mitochondrial metabolism;Molecular;monocyte;Normal Cell;novel;Nucleotides;Open Reading Frames;Oxidative Phosphorylation;Peptides;Physiological;polysome profiling;Preparation;prevent;Procedures;Protein Biosynthesis;Protocols documentation;Regulation;Research;Resolution;Ribonucleases;Ribosomal RNA;ribosome profiling;Ribosomes;RNA;Role;self-renewal;stem cell differentiation;stem cells;Sucrose;Techniques;Technology;Time;Tissue Sample;Tissues;tool;transcriptome sequencing;transcriptomics;Translating;translation factor;Translation Initiation;Translational Regulation;Translations;Ultracentrifugation;usability;Work

PROJECT_TITLE: An ultra-low-input RNase footprinting assay to quantify cytosolic and mitochondrial translation simultaneously

STUDY_SECTION: GCAT

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Genetics

ORG_CITY: DURHAM

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Public health relevance The goals of this project are to uncover genetic and cellular mechanisms controlling the maturation of apical membrane polarization and apical endocytosis during development of the vertebrate intestine. This project will help understand the origin of diseases associated with impaired absorption and cell polarity defects in the digestive tract, such as cancer, nutrient malabsorption, and congenital diarrheal disorders.

PI_NAMEs: BAGNAT, MICHEL  (contact)

PROGRAM_OFFICER_NAME: SENGER, STEFANIA

PROJECT_TERMS: absorption;Affect;Amino Acids;Apical;apical membrane;Automobile Driving;basolateral membrane;Biological;Cell Polarity;Clathrin Adaptors;Complex;Data;Defect;Degradation Pathway;Dependence;Development;Diarrhea;Dietary Proteins;Digestion;Disease;Endocytosis;Endosomes;Enterocytes;Epithelial Cells;Epithelium;fluorescence imaging;Food;forward genetics;Gastrointestinal tract structure;Genes;Genetic;Genetic Screening;glycosylation;Goals;Golgi Apparatus;Homeostasis;Impairment;improved;in vivo;Intestinal Absorption;intestinal epithelium;intestinal maturation;Intestines;intrinsic factor-cobalamin receptor;Introns;Ion Channel;Lipids;Lysosomes;Malabsorption Syndromes;Malignant Neoplasms;Membrane Proteins;Membrane Transport Proteins;Minor;Modeling;Morphology;mRNA Precursor;Mucins;mutant;Mutation;NGFR Protein;Nutrient;nutrient absorption;organ growth;particle;Pathway interactions;Physiological;Physiology;Play;Polysaccharides;Process;Protein Glycosylation;Protein Sortings;Proteins;Proton-Translocating ATPases;public health relevance;receptor;Regulation;RNA Splicing;Role;segregation;Sorting;sugar;superresolution microscopy;Surface;System;Systemic disease;Testing;trafficking;Transcript;transcriptional coactivator p75;transcriptome sequencing;Transmembrane Transport;uptake;vacuolar H+-ATPase;Vacuole;Visual;Zebrafish

PROJECT_TITLE: Developmental regulation of epithelial polarization by pre-mRNA splicing

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


NIH_SPENDING_CATS: Autoimmune Disease;Complementary and Integrative Health;Dietary Supplements;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Microbiome;Nutrition;Prevention

ORG_CITY: ANN ARBOR

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative We have shown that the absence of sufficient dietary fiber triggers an increase in the abundance of mucus degrading bacteria in the colon, leading to erosion of the protective mucus layer and higher susceptibility to development of inflammatory bowel disease (IBD). The goal of the proposed work is to determine the host and bacterial mechanisms involved in disease development and to investigate a newly revealed connection between dietary soy protein and production of an anti-inflammatory metabolite called isobutyrate. This knowledge will be used to improve gastrointestinal health and treat or prevent chronic disease such as IBD and colorectal cancer.

PI_NAMEs: CHEN, GRACE Y.;MARTENS, ERIC C (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Affect;Amino Acids;Animals;Anti-Inflammatory Agents;Bacteria;bacterial metabolism;Bacteroides;Bacteroides thetaiotaomicron;branched chain fatty acid;Butyrates;Caseins;Cells;Chronic Disease;Citrobacter rodentium;Clinical;Colitis;Colon;Colorectal Cancer;commensal bacteria;Complex;Complex Mixtures;Consumption;cytokine;Data;Defect;Degradation Pathway;deprivation;Development;Diet;Diet and Nutrition;dietary;Dietary Factors;Dietary Fiber;Digestion;Disease;Disease Progression;Disease susceptibility;disorder prevention;disorder risk;Enteral Nutrition;Environmental Risk Factor;Epithelial Cells;Epithelium;Equilibrium;Etiology;experimental study;feeding;Fermentation;Fiber;Foundations;gastrointestinal;Genetic;genetic approach;Genetic Polymorphism;Genetic Predisposition to Disease;Germ-Free;Glycoproteins;glycosylation;Gnotobiotic;Goals;Goblet Cells;gut bacteria;gut microbiota;Health;Health Benefit;Human;Human Genetics;Immune;improved;In Vitro;in vivo;Inflammation;Inflammatory Bowel Diseases;insight;Integration Host Factors;Interleukin-10;Intestines;Knockout Mice;Knowledge;Left;loss of function;Measures;Metabolic;microbial;microbial community;microbiome;microbiota;microbiota composition;Modeling;Molecular Genetics;Molecular Weight;mouse model;Mucins;Mucous body substance;Mucous Membrane;Mus;novel therapeutics;Nutrient;Organoids;pathogen;Pathway interactions;Peptides;Play;Polysaccharides;Population;Positioning Attribute;Predisposition;prevent;Process;Production;Proteins;Proteolysis;Proteomics;Reducing diet;Resort;Role;Series;Source;soy;Soy Proteins;Stable Isotope Labeling;Testing;Therapeutic;Thick;transcriptome sequencing;Valine;Variant;Volatile Fatty Acids;Work

PROJECT_TITLE: Dietary fiber and soy protein-based microbiome metabolites for IBD prevention

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-H(03)]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Clinical Research;Dissemination and Implementation Research;Nutrition;Obesity;Prevention;Social Determinants of Health

ORG_CITY: DAVIS

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: NARRATIVE Stores provide over two-thirds of calories and added sugar in the US diet, and product placement within stores influences consumer decisions. A policy that prohibits high-sugar and high-sodium products at store checkouts has the potential to reduce population risk of obesity and type 2 diabetes by lowering consumption of sugar- sweetened beverages, candy, sweets, and salty snacks—the most common foods and beverages at checkout. This project will evaluate the impact of the nation’s first healthy checkout policy on the healthfulness of store food environments and food and beverage sales, and it will examine implementation factors that influence policy effectiveness.

PI_NAMEs: FALBE, JENNIFER  (contact)

PROGRAM_OFFICER_NAME: EVANS, MARY

PROJECT_TERMS: Adopted;Advocate;Affect;Area;Authorization documentation;Behavior;Beverages;Calories;Candy;Cities;Code;Consolidated Framework for Implementation Research;Consumption;cost;Country;Dairying;Data;Diet;Dietary Fiber;Disease;Effectiveness;Environment;Ethnic Origin;Evaluation;experience;Fabaceae;Food;food environment;Fruit;implementation barriers;implementation determinants;implementation evaluation;improved;Income;Influentials;innovation;Intervention;Interview;Knowledge;Laws;Licensing;Methods;Natural experiment;Neighborhoods;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuts;obesity risk;Outcome;Policies;Policy Maker;Population;post implementation;Prevalence;Proxy;Public Health;Race;Reaction;Research;Sales;Sampling;Sodium;soft drink;sugar;Surveys;sweetened beverage;tool;Vegetables

PROJECT_TITLE: Impact of a Healthy Checkout Policy on Healthfulness of Grocery Environments and Sales

STUDY_SECTION: SSPB

STUDY_SECTION_NAME: Social Sciences and Population Studies B Study Section[SSPB]


ADMINISTERING_IC: EB

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Building Research Capacity at Institutions with Limited NIH Funding;Clinical Research;Regenerative Medicine

ORG_CITY: Chicago

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Bioengineering Experience for Science Teachers “BEST” Program NARRATIVE Meaningful professional development for teachers requires a focus on specific academic subject matter as well as pedagogical knowledge. A research experience in a bioengineering laboratory at a major research university can enhance knowledge of a high school teacher, making it possible to more effectively communicate the nature of bioengineering concepts and applications to his or her students. In combination with guided instruction in developing Next Generation Science Standard- aligned curriculum, the laboratory research can be translated and applied in high school classrooms using research-supported pedagogical practices.

PI_NAMEs: KOTCHE, MIIRI  (contact)

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: Biocompatible Materials;Biomedical Engineering;biomedical imaging;Career Choice;Chicago;college;Common Core;Communication;Communities;Community of Practice;curriculum development;Development;Education;Educational Curriculum;Educational process of instructing;Educational workshop;Engineering;Enrollment;experience;Faculty;faculty mentor;Goals;high school;High School Faculty;Illinois;improved;Instruction;Knowledge;Laboratories;Laboratory Research;learning materials;low socioeconomic status;Maps;Microfluidics;Modeling;nanobiomaterial;Nature;Neighborhoods;Next Generation Science Standards;Participant;peer;Population;programs;Regenerative Medicine;rehabilitation engineering;Research;Research Support;Resources;scaffold;Schools;science teacher;Self Efficacy;skills;Students;summer research;teacher;Teacher Professional Development;Teaching Materials;Training;Translating;Underrepresented Minority;Underrepresented Students;United States National Institutes of Health;Universities

PROJECT_TITLE: BEST Program:  Bioengineering Experience for Science Teachers


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: IRVINE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative C. difficile toxin B (TcdB) is a dominant virulence factor contributing to diseases associated with C. difficile infection (CDI). However, TcdB sequence variations pose a challenge in developing effective therapeutics for the treatment of CDI. Here we seek to develop receptor-decoy-based therapeutic proteins that block a broad range of toxins, as well as novel vaccine candidates that provide effective protection again most of the known TcdB variants.

PI_NAMEs: JIN, RONGSHENG  (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Address;Affinity;Animal Model;Animals;anti-toxin;Antibiotic Therapy;Antibiotics;Antibodies;antibody mimetics;Antigens;Binding;Binding Sites;Biology;Cells;Clinical;clinical sequencing;Clostridium difficile;Collaborations;Colon;Complex;Cryoelectron Microscopy;CSPG4 gene;design;Developed Countries;Disease;Environment;Epitopes;Escape Mutant;Extracellular Domain;Face;Failure;Family;FDA approved;Formaldehyde;gastrointestinal infection;Generations;Goals;gut microbiota;Healthcare;holotoxins;Hospitalization;Human;Immune response;Immunize;In Vitro;in vivo;Infection;infection risk;Knowledge;Mediating;Membrane;Molecular;Monoclonal Antibodies;Mus;neutralizing antibody;neutralizing monoclonal antibodies;neutralizing vaccine;North America;novel strategies;novel vaccines;opportunistic pathogen;Passive Immunotherapy;Pathogenesis;pathogenic bacteria;patient population;Patients;Phase;Phase I/II Trial;prevent;Prevention;Productivity;prophylactic;protein complex;Protein Engineering;Proteins;prototype;rational design;receptor;receptor binding;Recovery;Recurrence;Recurrent disease;Relapse;Reproduction spores;Resistance;Ribotypes;seal;Site;Speed;standard of care;structural biology;Structural Protein;Structure;Therapeutic;therapeutic development;therapeutic protein;therapeutically effective;Toxin;Toxoids;vaccine candidate;vaccine development;vaccine strategy;Vaccines;Variant;Virulence Factors

PROJECT_TITLE: Developing broad-spectrum therapeutics against C. difficile toxins

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering;Physical Injury - Accidents and Adverse Effects;Rehabilitation

ORG_CITY: HINES

ORG_NAME: CHICAGO ASSN FOR RESEARCH & EDUC IN SCI

PHR: Extensor tendon injuries of the hand are more common than anterior cruciate ligament injuries. Outcomes after treatment vary, with some patient reported outcomes reporting the same quality of life as two and five finger amputees. The goal of this research is to understand the causes of the functional deficits with a view towards improving patient outcomes following extensor tendon injury.

PI_NAMEs: MURIUKI, MUTURI G (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Affect;Aftercare;Algorithms;Amputees;Analysis of Variance;Anatomy;anterior cruciate ligament injury;Biomechanics;Cadaver;Catalogs;Clinical Treatment;Communication;Data;Development;disability;experimental group;Experimental Models;experimental study;Extensor;Fingers;Flexor;General Population;Goals;grasp;Grooming;Hand;hand dysfunction;Hand functions;Hand Injuries;Hand Strength;Hygiene;improved;Incidence;Injury;Interruption;Laceration;mathematical model;Measures;model development;Modeling;Motion;Occupational;Operative Surgical Procedures;Outcome;Outcome Assessment;outcome prediction;Output;Patient Outcomes Assessments;Patient-Focused Outcomes;Patients;Pattern;Persons;Play;Procedures;Quality of life;Recreation;Reporting;Research;Role;Rotation;Running;Severities;sex;skeletal tissue;Skin;soft tissue;Specimen;Surface;System;Tendon Injuries;Tendon structure;Time;tool;Trauma;treatment and outcome;treatment optimization;Treatment outcome;Variant;Work

PROJECT_TITLE: Combined Experimental and Analytical Study of the Effects of Zone V Extensor Tendon Injuries on Hand Function

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Parkinson's disease (PD) is recognized as the second most common age-related neurodegenerative disorder after Alzheimer's disease, affecting up to 1% of the population above the age of 60 and 4-5% above the age of 85. According to the National Institute of Health, about 1 million people in the United States are suffering from PD. Mutations in LRRK2 are known to be the most common genetic causes of PD. Elucidation of the molecular regulation of LRRK2 in PD in this proposal will lead to understanding how the regulation affects the actions of LRRK2 in nigrostriatal pathway. Accomplishment of this study will advance our understanding of the physiologic and pathophysiologic actions of LRRK2 as well as identification of novel therapeutic targets for LRRK2-associated PD.

PI_NAMEs: XIONG, YULAN  (contact)

PROGRAM_OFFICER_NAME: SWANSON-FISCHER, CHRISTINE R

PROJECT_TERMS: Affect;Age;age related neurodegeneration;Alzheimer's Disease;Attention;Behavior;behavior test;Behavioral;behavioral phenotyping;Biology;Cell Physiology;Complex;Corpus striatum structure;Data;Defect;Dimerization;Disease;Disease Progression;disease-causing mutation;dopaminergic neuron;Drosophila genus;Drug Targeting;Future;Genetic;Goals;GTP Binding;GTPase-Activating Proteins;guanine nucleotide binding protein;Guanine Nucleotide Exchange Factors;Guanosine Triphosphate Phosphohydrolases;In Vitro;in vivo;Induced Neurons;interest;Intervention;Investigation;kinase inhibitor;Knowledge;Link;LRRK2 gene;Membrane;Molecular;Monitor;Movement Disorders;Mus;Mutation;Neuroanatomy;Neurons;neurotoxicity;new therapeutic target;nigrostriatal pathway;novel;Nucleotides;Parkinson Disease;pars compacta;Pathogenesis;Pathologic;Pathology;Pattern;Persons;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;Physiological;Population;Proteins;Regulation;Role;Substantia nigra structure;Symptoms;targeted treatment;Testing;Therapeutic;therapeutic development;United States;United States National Institutes of Health

PROJECT_TITLE: Molecular Regulation of LRRK2 in Parkinson's Disease

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Prevention;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Abdominal aortic aneurysm (AAA) is a life-threatening condition which affects ~4% of the population ≥ 65 years of age and for which the only efficacious intervention is surgery. Emerging evidence implicates a causal role for low density lipoprotein cholesterol (LDL-C) and suggests that the intensive LDL-C lowering with PCSK9 inhibitors may be a potential strategy to prevent and treat AAA. This project will integrate human genetic evidence and a mechanistic clinical trial to obtain data that would support conducting a large-scale efficacy trial in humans.

PI_NAMEs: DAMRAUER, SCOTT MICHAEL (contact)

PROGRAM_OFFICER_NAME: REID, DIANE M

PROJECT_TERMS: Abdominal Aortic Aneurysm;Affect;Age Years;ancestry analysis;Aneurysm;Anti-Inflammatory Agents;Aorta;Atherosclerosis;Biological Assay;blind;cell type;Cessation of life;Chronic;Clinical;Clinical Trials;cohort;cytokine;Data;design;Development;Dilatation - action;efficacious intervention;efficacy clinical trial;efficacy evaluation;efficacy trial;Enzymes;European ancestry;Experimental Models;experimental study;Familial Hypercholesterolemia;Future;Gelatinase B;Genetic;genetic approach;genome wide association study;genome-wide;Growth;Human;Human Genetics;human old age (65+);human subject;Hyperlipidemia;immune cell infiltrate;Immunofluorescence Immunologic;Individual;Inflammation;Inflammatory;inhibitor;Interleukin-6;Knowledge;LDL Cholesterol Lipoproteins;Life;Link;Lipids;Low Density Lipoprotein Receptor;Low-Density Lipoproteins;Macrophage;Measurement;Measures;Medical;Meta-Analysis;monocyte;operation;Operative Surgical Procedures;Organ Donor;Pharmaceutical Preparations;Pharmacogenetics;pharmacologic;Pharmacological Treatment;Placebo Control;Placebos;Population;Positioning Attribute;prevent;Prevention;primary outcome;Production;Proprotein Convertases;Randomized;Randomized, Controlled Trials;repaired;Reporting;Research;Risk;Role;Rupture;Schedule;secondary outcome;Secondary Prevention;single nucleus RNA-sequencing;Smooth Muscle Myocytes;Subcutaneous Injections;Subtilisins;Testing;Therapeutic;Time;Tissues;transcriptome sequencing;United States;Variant;Work

PROJECT_TITLE: Impact of PCSK9 inhibition on abdominal aortic aneurysm pathobiology and growth

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_DEPT: OTHER BASIC SCIENCES

PHR: Project Narrative For those over 65, age represents the highest risk factor for Alzheimer’s disease (AD) and our National Plan to Address Alzheimer’s Disease makes clear the need for early identification and monitoring of the disease, its progress, and any treatments. There is a critical need for a highly sensitive measure of hippocampal function to assess change in memory and hippocampal function over time, both for monitoring of disease progression and to evaluate the effectiveness of treatment approaches. The development of the clinical Mnemonic Similarity Task will improve sensitivity compared to existing neuropsychological assessments, making it an extremely valuable tool for tracking progression of disease or decline and critical for determining the effectiveness of treatments, both pharmaceutical and behavioral.

PI_NAMEs: STARK, CRAIG E (contact)

PROGRAM_OFFICER_NAME: TREVINO, MELISSA

PROJECT_TERMS: Address;Adopted;Adult;Age;age group;age related;Aging;Alzheimer's Disease;Alzheimer's disease risk;Amyloid beta-Protein;Bayesian Analysis;Behavioral;Biological Assay;Biological Markers;Clinical;clinical development;Clinical Distribution;Clinical Research;Clinical Trials;clinically relevant;Cognitive;cognitive testing;cohort;Consent;Data;Data Collection;Databases;Dementia;design;Development;Devices;diagnostic screening;diagnostic value;Discrimination;Disease;Disease Progression;early detection biomarkers;Early identification;effectiveness evaluation;Elderly;Encapsulated;Ethnic Origin;Evaluation;Exercise;Exhibits;Functional disorder;Goals;Healthcare;healthy aging;high risk;Hippocampus;human old age (65+);Impairment;improved;Individual;Investigation;Japanese;laptop;large scale data;Levetiracetam;life span;Link;longitudinal design;Magnetic Resonance Imaging;Measures;Medicare;Memory;Memory impairment;Memory Loss;memory recognition;Methods;mild cognitive impairment;Modeling;Monitor;Neuropsychological Tests;Neuropsychology;object recognition;older adult;Pattern;Performance;Persons;Pharmacologic Substance;Population;Publications;Race;Reporting;Research;Sampling;Screening procedure;Standardization;Stimulus;Structure;Surveys;Tablets;tau Proteins;Testing;Time;tool;touchscreen;Training;Treatment Effectiveness;Validation;Variant;wellness visit

PROJECT_TITLE: Development of the mnemonic similarity task as a tool to address age and dementia-related memory decline

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biomedical Imaging;Biotechnology;Genetics;Physical Injury - Accidents and Adverse Effects

ORG_CITY: LOS ANGELES

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE The proposed project aims to explore how radiation damage drives systemic immune imbalances and late organ damage and how this interfaces with changes in circulating miRNA signatures. Ultimately, our goal is to tease out which of these miRNA changes are specific for acute and late radiation tissue damage and build a biomarker panel that would inform on triage decisions after a radiological incident. The appeal in being able to predict the propensity of an exposed individual for developing late effects in a tissue-specific manner after irradiation can not be overstated, and the relevance of these studies may additionally extend to patients receiving cancer radiotherapy.

PI_NAMEs: SCHAUE, DORTHE  (contact)

PROGRAM_OFFICER_NAME: VEDAMONY, MERRILINE M

PROJECT_TERMS: Acute;Address;Age;Animal Model;Animals;Attention;Autopsy;biodosimeter;biological adaptation to stress;Biological Assay;Biological Markers;biomarker panel;Blood;Body Weight;Bone Marrow;cancer radiation therapy;candidate marker;Caring;Cessation of life;Characteristics;Chemicals;Chronic;circulating microRNA;clinical examination;Complex;coronary fibrosis;Cox Proportional Hazards Models;Data;data mining;Dependence;Development;Diagnosis;Disease;Dose;Dose Rate;Echocardiography;Event;experience;Exposure to;Fright;Gender;Goals;Heart;heart damage;Hematopoietic;High-LET Radiation;Histology;Homeostasis;Human;Immune;Immune system;Immune System Diseases;Immunology;improved;in vivo;Inbred C3H Mice;Incidence;Individual;Inflammation;Inflammatory;Infrastructure;Investigation;Ionizing radiation;irradiation;Kidney;Knowledge;Late Effects;life span;Liver;Lung;lung injury;male;Measurable;Medical;MicroRNAs;mindfulness;miRNA expression profiling;Modeling;Monitor;Morbidity - disease rate;mortality;Mus;Myeloid Cells;Nature;Neutrons;nonhuman primate;Normal tissue morphology;novel;Nuclear;Organ;Outcome;Pancreas;Pancreatic enzyme;Pathway interactions;Patients;Pattern;Persons;Plasma;Population;premature;Prognosis;Quantitative Reverse Transcriptase PCR;Radiation;Radiation Accidents;radiation effect;Radiation exposure;Radiation induced damage;Radiation Injuries;Radiation Physics;Radiation Toxicity;radiation-induced tissue damage;Radiobiology;Radiometry;Recurrence;Research;response;Risk;Roentgen Rays;Screening procedure;Signal Transduction;Statistical Data Interpretation;statistics;Survivors;System;Terrorism;Time;Tissues;Toxic effect;Triage;Veterinary Medicine;Whole-Body Irradiation;Work;X-Ray Computed Tomography

PROJECT_TITLE: Acute radiation injury alters microRNA profiles that predict late tissue-specific damage


NIH_SPENDING_CATS: Adolescent Sexual Activity;Biotechnology;Cancer;Cervical Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;HPV and/or Cervical Cancer Vaccines;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Infectious Diseases;Microbiome;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Sexually Transmitted Infections;Vaccine Related;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: PEDIATRICS

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Minority youth have the highest rates of sexually transmitted infections (STIs), including human papillomavirus (HPV) and chlamydia. This study will investigate the real-world effectiveness of the HPV vaccines in an inner- city population of adolescent and young adult women of color. In addition, this study will evaluate the impact of the cervicovaginal microbial environment on the risks of HPV and STIs.

PI_NAMEs: BURK, ROBERT D;DIAZ, ANGELA  (contact);SCHLECHT, NICOLAS

PROGRAM_OFFICER_NAME: CHUANG, ELEANORE JENNIFER

PROJECT_TERMS: Address;Adolescent;Adolescent and Young Adult;adolescent health;Adult women;African American;Age;Antibody titer measurement;Anus;Bacterial Vaginosis;Biological;Biological Assay;Black race;booster vaccine;breakthrough infection;Caring;Cells;Cervical;cervicovaginal;cervicovaginal microbiome;Chlamydia;Chlamydia trachomatis;Clinical Research;Clinical Trials;cohort;Cohort Effect;Cohort Studies;Collection;cytokine;Data;design;Detection;Effectiveness;Enrollment;Environment;epidemiology study;Escape Mutant;Etiology;Female;Female Adolescents;follow-up;Follow-Up Studies;Funding;Genetic;Genetic Variation;Gonorrhea;Hispanic;HPV-High Risk;Human papilloma virus infection;Human Papilloma Virus Vaccination;Human Papilloma Virus Vaccine;Human Papillomavirus;Human papillomavirus 16;Human papillomavirus HPV L1 protein;Immunization;immunogenicity;Immunoglobulin G;Incidence;Infection;inner city;Interleukin-1 beta;Interleukin-10;Longitudinal Studies;Longterm Follow-up;Measures;Mediation;Methods;microbial;minority children;Minority Groups;Minority Women;Molecular;Mutation;Natural History;Nature;next generation sequencing;novel;Oral;oral HPV;Participant;Patients;Population;Prevalence;Productivity;prospective;Protocols documentation;recruit;Recurrence;Reporting;Risk;Risk Behaviors;Risk Factors;safety study;Sampling;screening;Serum;sexual debut;Sexually Transmitted Diseases;Specimen;Syphilis;Time;TNF gene;Trichomonas;Vaccination;vaccine effectiveness;vaccine trial;Vaccinee;Vaccines;Viral;Virus;Woman;women of color;Women's cohort;young adult

PROJECT_TITLE: Cervical, Anal & Oral HPV Persistence/Adolescent Girls

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-A(90)S]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Cystic Fibrosis;Emerging Infectious Diseases;Infectious Diseases;Lung;Rare Diseases

PHR: PROJECT NARRATIVE The environmental bacterium Stenotrophomonas maltophilia is now recognized as a significant, multi-drug resistant pathogen, but it remains greatly understudied. Our data document that S. maltophilia has a type IV secretion system and two protein effectors that impact the viability of competing bacteria, including Pseudomonas aeruginosa, a prominent pathogen that can co-infect the human host. We hypothesize that these secreted proteins influence microbial interactions during infection and may be potential tools for disease control, and therefore the proposed studies are aimed at defining how these novel secreted effectors function and on what other important microbial competitors.

PI_NAMEs: CIANCIOTTO, NICHOLAS P (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Achromobacter xylosoxidans;Anti-Bacterial Agents;Antibiotics;antimicrobial;Apoptosis;Aspergillus fumigatus;Bacteria;bactericide;Binding;Bioinformatics;Biological Assay;Burkholderia cepacia;C-terminal;Cell Death;Cells;Cessation of life;Clinical;Consensus Sequence;Coupling;COVID-19 patient;cystic fibrosis patients;Data;Development;disorder control;emerging human pathogen;enzyme activity;Enzymes;Epithelial Cells;Escherichia coli;fungus;Genes;Haemophilus influenzae;Hospitals;Human;human pathogen;Hybrids;Immunity;Impairment;improved;Individual;Infection;Knowledge;Link;Lipase;Lipids;Lung;Macrophage;Measures;Mediating;Medical;Membrane;Microbe;microbial;microorganism interaction;multi-drug resistant pathogen;Muramidase;mutant;N-Acetylmuramoyl-L-alanine Amidase;novel;pathogen;Pathogenesis;Peptidoglycan;periplasm;Pneumonia;Protein Secretion;Protein translocation;Proteins;Pseudomonas aeruginosa;Pulmonary Cystic Fibrosis;Ralstonia;Reporting;Research Project Grants;Resistance;Risk;Role;Staphylococcus aureus;Stenotrophomonas maltophilia;System;Testing;three dimensional structure;tool;Type IV Secretion System Pathway;United States National Institutes of Health;Water;Work

PROJECT_TITLE: Stenotrophomonas maltophilia TfcA and TfcB: Antibacterial T4SS effectors from an emerging human pathogen

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


NIH_SPENDING_CATS: Antimicrobial Resistance;Digestive Diseases;Infectious Diseases;Rare Diseases

ORG_CITY: WASHINGTON

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Narrative Hookworms are parasitic worms of global importance, infecting nearly 500 million poor people, and causing serious anemia in children, pregnant woman, woman of childbearing age, and the elderly. Current control depends on drugs to which other parasitic worms have already become resistant. We will investigate the mechanism of resistance to one of these drugs, pyrantel, using a resistant hookworm strain we have isolated.

PI_NAMEs: HAWDON, JOHN M (contact);O'HALLORAN, DAMIEN M

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Albendazole;Anemia;Anthelmintics;Area;benzimidazole;benzimidazole resistance;Caenorhabditis elegans;Canis familiaris;Child;cognitive development;companion animal;CRISPR/Cas technology;Cues;Data;Defect;Dependence;Depressed mood;Detection;Developing Countries;Development;DNA Sequence Alteration;Drug resistance;Elderly;Event;Exploratory/Developmental Grant;Exposure to;Family;feeding;Female of child bearing age;Filarial Elephantiases;Genes;Genetic;Guanylate Cyclase;Heat shock factor;Heat shock proteins;Heat-Shock Proteins 90;Heat-Shock Response;Helminths;Hookworm Infections;Hookworms;Human;In Vitro;Incubated;Individual;Infection;inhibitor;insight;Intervention;Iron deficiency anemia;Ivermectin;Larva;Link;Livestock;member;Membrane;Molecular;Molecular Chaperones;Monitor;Morbidity - disease rate;Mutation;Names;Nature;Nematoda;novel;Orthologous Gene;Parasitic nematode;Pathway interactions;Periodicals;Persons;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Population;Predisposition;Pregnant Women;pressure;programs;Public Health;Pyrantel;receptor;Resistance;Resistance development;resistance mechanism;resistant strain;response;Role;Signal Transduction;Single Nucleotide Polymorphism;Soil;Temperature;Testing;Time;tool;transmission process;Virulent;whole genome

PROJECT_TITLE: Dissecting the mechanism of pyrantel resistance in hookworm

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-B(82)]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: IOWA CITY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative DNA damage interferes with DNA replication leading to genome instability – the hallmarks of cancer, aging, and other diseases. The long-term goal of our research program is to understand DNA damage bypass pathways, such as translesion synthesis and template switching, which help mitigate the effects of DNA damage during replication. Our proposed studies are relevant to public health because they will provide important insights into the maintenance of genome stability.

PI_NAMEs: WASHINGTON, M. TODD (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Aging;Biochemical;Biological;Biophysics;Bypass;Cells;Chromosomal Rearrangement;Complex;coping;Disease;DNA biosynthesis;DNA Damage;DNA replication fork;Ensure;Enzymes;Eukaryota;Genome Stability;Genomic Instability;Goals;helicase;insight;Maintenance;Malignant Neoplasms;Multiprotein Complexes;Mutation;Pathway interactions;Polymerase;Positioning Attribute;Process;programs;Public Health;Regulation;Research;System;tool

PROJECT_TITLE: Structural and Mechanistic Studies of DNA Damage Bypass Pathways in Eukaryotes


ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative Cell-adhesion receptors are key molecules for cellular communication and have emerging functions in numerous cellular processes. The research proposed in this application will yield key insights into fundamental molecular mechanisms that underlie the function of two poorly understood families of cell-adhesion receptors in multicellular organisms (namely the 33 adhesion G Protein-Coupled Receptors (aGPCRs) and the four teneurins). This research will provide critical knowledge into the molecular mechanisms of intercellular communication, and since many aGPCRs and teneurins are found mutated in neurological disorders and cancers, this research is expected to provide crucial clues for the development of novel strategies to understand and treat these disorders.

PI_NAMEs: ARAC-OZKAN, DEMET  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: adhesion receptor;Adhesions;Biochemical;Biological Assay;Biophysics;brain malformation;Cell Adhesion;Cell Physiology;Cell Surface Receptors;Communication;Communities;Complex;Development;developmental disease;Disease;Eukaryota;Evolution;extracellular;Family;FDA approved;Future;G-Protein-Coupled Receptors;Genetic study;Goals;Heart;human disease;insight;intercellular communication;interdisciplinary approach;Knowledge;Ligands;Link;Malignant Neoplasms;malignant neurologic neoplasms;Mediating;Molecular;Mutagenesis;Mutate;Nature;nervous system development;Nervous System Disorder;novel strategies;Organism;Pharmaceutical Preparations;Physiological;programs;Protein Engineering;receptor;receptor function;Research;Role;Signal Transduction;Skeletal system;Structure;success;Testing;Therapeutic;three dimensional structure;tool;Work

PROJECT_TITLE: Structural and Functional Studies of Cell-Adhesion Receptors

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


NIH_SPENDING_CATS: HIV/AIDS;Human Fetal Tissue;Infectious Diseases

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: PROJECT NARRATIVE Although antiretroviral drugs can suppress HIV infection, these drugs do not eliminate latently infected cells that resupply active virus and thus require life-long administration with cost, compliance, resistance and chemo- exposure concerns. Combining computer-based design, synthesis, medicinal chemistry and state-of-the-art in vitro and in vivo modeling, the proposed studies will evaluate a new concept and new compounds for reversing HIV latency including conceptually new analog and prodrug latency reversing agents (LRAs) representing the most effective and best tolerated LRAs thus far, determine mechanistic requirements for their LRA activation using PKC inhibitors and transcriptomic analyses, determine synergies and tolerabilities between our new and known LRAs, and test the best performing LRAs or LRA combinations with kill components in an integrated kick and kill strategy evaluation, collectively serving as a preclinical prelude for HIV eradication and clinical evaluation.

PI_NAMEs: WENDER, PAUL ANTHONY;ZACK, JEROME A. (contact)

PROGRAM_OFFICER_NAME: SANDERS, BRIGITTE E

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;analog;Animal Model;Anti-Retroviral Agents;antiretroviral therapy;Area;benzotriazole;Biodistribution;bryostatin;Cells;Cellular biology;chemical synthesis;Chemicals;Clinical;Comparative Study;Computers;cost;cytokine;design;Disease Progression;Dose;Drug or chemical Tissue Distribution;Effector Cell;efficacy evaluation;Esters;Evaluation;Family;Generations;Goals;Health;Histone Deacetylase;HIV;HIV Infections;HIV/AIDS;humanized mouse;Immune;improved;In Vitro;in vitro Assay;in vivo;in vivo Model;Individual;Infection;inhibitor;Interruption;Laboratories;Libraries;Life;Mediating;mimetics;mouse model;Natural Killer Cells;next generation;NF-kappa B;Noise;novel;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;Plasma;pre-clinical;preclinical development;Prodrugs;programs;prostratin;protein farnesyltransferase;Protein Isoforms;Protein Kinase C;Protein Kinase C Inhibitor;Proviruses;Publishing;purge;Regimen;Reporting;research clinical testing;Resistance;scaffold;Science;Signal Pathway;Source;Structure;synergism;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Toxic effect;Transcriptional Activation;transcriptomics;Viral Cytopathogenic Effect;Viral load measurement;Viral reservoir;virology;Virus;Virus Latency;Virus Replication;Work

PROJECT_TITLE: Towards HIV eradication: New concepts and potent compounds for PKC-mediated latency reversal

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


ORG_CITY: GALVESTON

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: Project Narrative Mutational inactivation of translesion synthesis DNA polymerases and of the protein factors that function with them cause an increase in cancer proneness. Our studies will provide an understanding of the mechanisms via which intrinsically error-prone translesion synthesis DNA polymerases are made to conduct predominantly error- free replication through DNA lesions in human cells – essential for cellular homeostasis and genome stability.

PI_NAMEs: PRAKASH, LOUISE  (contact)

PROJECT_TERMS: Active Sites;Affect;ATP phosphohydrolase;Biochemical;Cell Physiology;Cells;Chromosomal Instability;Cryoelectron Microscopy;DNA biosynthesis;DNA lesion;DNA-dependent ATPase;DNA-Directed DNA Polymerase;Excision;Family;Genetic;genome integrity;Genome Stability;genome-wide;helicase;Homeostasis;Human;Label;Malignant Neoplasms;Molecular;Mutation;Nucleotides;Phosphodiesterase I;Play;Polymerase;prevent;protein function;Proteins;replicase;Research;restraint;Role;tumorigenesis;WRN gene;Y protein

PROJECT_TITLE: Mechanisms for the high fidelity of translesion synthesis by Y-family DNA polymerases in human cells

STUDY_SECTION: MRAA

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


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_DEPT: VETERINARY SCIENCES

PHR: Abnormalities in cell migration lead to severe developmental defects and contribute to numerous disease states, including heart disease and cancer - the two leading causes of death in the United States. The current proposal will delineate the mechanistic basis for novel regulation of cell migration by novel mechanisms including actin coding sequence and posttranslational arginylation, with the goal of enabling the development of new therapeutics that regulate aberrant cell migration and adhesion in these disease states.

PI_NAMEs: KASHINA, ANNA S (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Actins;Base Sequence;beta Actin;Biological;Cause of Death;Cell Adhesion;cell motility;cell type;Cells;Cellular biology;Code;Data;Defect;Development;Disease;Ensure;Enzymes;Event;Exhibits;extracellular;gamma Actin;Gene Transfer Techniques;Goals;Heart Diseases;Immune response;in vivo;Lead;Malignant Neoplasms;Messenger RNA;Microfilaments;migration;Morphogenesis;Mus;N-terminal;Neoplasm Metastasis;novel;novel therapeutics;Nucleotides;Physiological Processes;Process;programs;Protein Biochemistry;Protein Isoforms;Proteins;Publishing;Regulation;Research;response;Specificity;Speed;Stimulus;Tissues;Translations;Ubiquitination;United States;virtual;Work

PROJECT_TITLE: Regulation of cell migration by nucleotide coding sequence and arginylation

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: FORT COLLINS

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: The Initiative to Maximize Student Development in Translational Medicine (IMSDTM) Training Program will recruit, matriculate and support diverse predoctoral students from underrepresented populations in biomedical research that translates to human clinical applications to address human health and disease globally. Trainees will benefit from the vast expertise of experienced mentors, state-of-the-art facilities, and substantial institutional programmatic resources and extra- mural funding. Together, activities to encourage inclusivity, synergism in training, and unique experiential opportunities will provide diverse cohorts of predoctoral trainees with the necessary skills to confront threats to human health as they embark upon academic or non-academic research careers in translational medicine research.

PI_NAMEs: CROSS, JENNIFER EILEEN;JOHN, GILBERT H (contact);ZABEL, MARK D

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - C[TWD-C]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Biotechnology;Brain Disorders;Eye Disease and Disorders of Vision;Neurosciences;Rehabilitation

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Sensory information influences how the brain develops and recovers from injury. We propose studies to investigate cellular mechanisms that operate during brain circuit development and during recovery from injury.

PI_NAMEs: CLINE, HOLLIS T. (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Address;Amblyopia;Animals;avoidance behavior;Behavior;Behavioral;Behavioral Assay;behavioral plasticity;Biological Assay;Brain;Brain Injuries;Cell Physiology;cohort;Date of birth;Development;developmental disease;Electrophysiology (science);Event;experience;experimental study;flexibility;Functional Imaging;genetic manipulation;Goals;Image;Impairment;in vivo;in vivo imaging;Induced Neurons;injured;Injury;injury recovery;insight;Investigation;Knowledge;Label;Mass Spectrum Analysis;Metabolic;Modeling;Molecular;Molecular Genetics;multidisciplinary;mutant;Nerve Degeneration;Nervous System;neural circuit;neurological rehabilitation;Neuronal Plasticity;Neurons;newborn neuron;novel;Optics;Photic Stimulation;Protein Biosynthesis;Protein Dynamics;Protein Synthesis Induction;Proteins;Proteomics;Protocols documentation;Recovery;Rehabilitation therapy;repaired;response;RNA Transport;RNA-Binding Protein FUS;RNA-Binding Proteins;Role;Sensory;Stimulus;structural imaging;superior colliculus Corpora quadrigemina;Synapses;synaptic function;System;Tadpoles;Tectum Mesencephali;Testing;Translations;treatment strategy;Untranslated RNA;Visual;Visual impairment;visual motor;Visual System;Western Blotting;Xenopus;Xenopus laevis

PROJECT_TITLE: Experience-dependent Cellular Plasticity Mechanisms

STUDY_SECTION: SYN

STUDY_SECTION_NAME: Synapses, Cytoskeleton and Trafficking Study Section[SYN]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Social Determinants of Health;Violence Research

ORG_CITY: BOSTON

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

ORG_STATE: MA

PHR: PROJECT NARRATIVE This project will pilot test an online class to promote healthy relationships for autistic adults. 160 autistic participants age ≥18 years old will be randomized to the class (HEARTS) or to an active control condition. The goal is to produce a new and innovative relationships intervention within a neurodiversity framework that is highly accessible, delivered at low cost, effective, and satisfying to participants.

PI_NAMEs: ROTHMAN, EMILY F (contact);WHITE, SUSAN WILLIAMS

PROGRAM_OFFICER_NAME: PUGLIESE, CARA ELISABETH

PROJECT_TERMS: 18 year old;active control;Adult;adult with autism spectrum disorder;Advocate;Affect;Age;autism spectrum disorder;autistic;Behavior;behavioral health;bullying;Child;Clinical;Clinical Trials;Collaborations;Communities;community based participatory approach;community setting;Consent;contextual factors;cost;Data;dating violence;design;Dropout;Education;Educational Curriculum;Educational process of instructing;Effectiveness;Enrollment;Ensure;epidemiologic data;evidence base;Evidence based intervention;experience;Exploration, Preparation, Implementation, and Sustainment;Eye;feasibility testing;Feeling;Feeling hopeless;Feeling suicidal;follow-up;Friends;Friendships;Goals;Grant;Health;Hybrids;Impairment;implementation design;implementation/effectiveness;improved;individuals with autism spectrum disorder;innovation;Intervention;K-18 conjugate;Life;Link;Loneliness;Manuals;Masks;Mediation;meetings;Mental Depression;Methods;Modeling;Motivation;National Institute of Mental Health;novel;online delivery;Outcome;Participant;patient engagement;Patients;Pediatric epidemiology;peer;peer violence;Persons;pilot test;Preparation;Program Appropriateness;programs;Provider;psychiatric symptom;public health relevance;Randomized;Randomized, Controlled Trials;recruit;Research;Sampling;satisfaction;Secondary to;Services;sex;Sex Orientation;sexual violence;skills;social;social anxiety;Social isolation;social skills;Strategic Planning;suicidal;teacher;teacher community;Teacher Professional Development;Testing;Thinking;Thinness;Time;Training;United States National Institutes of Health;Victimization;violence prevention;Vulnerable Populations;willingness;Work

PROJECT_TITLE: Healthy Relationships on the Autism Spectrum: Feasibility and Target Engagement

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


NIH_SPENDING_CATS: Genetics;Nutrition

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project Narrative Whether and how cells detect and respond to the presence of lipid stores is largely unknown. Here we define how factors modulating gene expression bind to cellular lipid droplets, and how such sequestration alters their response to available glucose in the medium. Because this gene expression network is of broad importance to mammalian metabolism, these findings will have a broad impact on our understanding of the consequences of cellular lipid accumulation.

PI_NAMEs: FARESE, ROBERT V;WALTHER, TOBIAS C (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: alpha-glycerophosphoric acid;Attenuated;Binding;Biochemical;Buffers;Carbohydrates;Cells;Cellular biology;Cellular Metabolic Process;Data;developmental disease;Dietary Fatty Acid;Dimerization;Esterification;Family;fascinate;Fatty Acids;Gene Expression;Genetic;Genetic Transcription;Glucose;glucose metabolism;glucose uptake;Health;Hepatocyte;Homeostasis;Human;insight;Intervention;Knowledge;Link;lipid biosynthesis;lipid metabolism;Lipids;Liver;member;Membrane;Metabolic;Metabolic Diseases;Metabolic syndrome;Metabolism;Modeling;Mus;novel;Nutrient;Obesity;Organelles;Organism;pandemic disease;Physiological;Physiology;Process;Regulation;response;Role;Surface;Testing;Therapeutic;transcription factor;Transcriptional Activation;Transcriptional Regulation;Triglycerides;Williams Syndrome

PROJECT_TITLE: Lipid Droplets and Transcriptional Regulation of Metabolism

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: TEMPE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because of a growing need to innovate the current Alzheimer’s Disease (AD) clinical trial recruitment and assessment process in order to enhance trial efficacy. We propose the application of an online video game as a potential enrichment tool to predict long-term declines in older adult cognition and daily function relevant to AD, thereby aligning with new initiatives in NIA to identify key behavioral patterns/signals that are sensitive and specific to AD. The online nature of this proposed research allows for a fast, affordable and engaging enrichment technique that is particularly timely in the context of COVID-19, where participants can participate remotely in their homes without physical face-to-face contact.

PI_NAMEs: HOOYMAN, ANDREW  (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: Age;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer’s disease biomarker;arm;Behavioral;Biological Assay;career;Characteristics;clinical heterogeneity;clinical trial recruitment;Clinical Trials;Cognition;Cognitive;Cognitive aging;cognitive change;cognitive function;cognitive testing;cohort;Collaborations;Consent;COVID-19;crowdsourcing;daily functioning;Data;design;Diagnosis;early detection biomarkers;Education;efficacy trial;Electronics;experience;FDA approved;Fingers;functional decline;Future;game development;Goals;handheld mobile device;Health;Home;Impaired cognition;improved;Individual;Infrastructure;innovation;interest;Investigation;Learning;Life Style;Measures;Mentorship;Modernization;Motor;Nature;Neuropsychology;next generation;non-demented;novel;older adult;Paired-Associate Learning;Participant;Patient Self-Report;Pattern;Performance;Persons;Play;Process Assessment;Prognosis;Public Health;Publishing;Questionnaires;Research;Risk Factors;Sampling;Sampling Studies;screening;Screening procedure;sex;Signal Transduction;Social Distance;success;Supervision;Surveys;Symptoms;Techniques;Testing;Time;tool;Training Activity;treatment response;Video Games;virtual laboratory;Vision;Work

PROJECT_TITLE: Using an Online Video Game to Predict Functional and Cognitive Decline within the MindCrowd Electronic Cohort


NIH_SPENDING_CATS: Chronic Pain;Infectious Diseases;Neurosciences;Pain Research

PHR: The goal of these studies is to understand how nerves in the skin may be silenced by parasitic worms found in contaminated soil when they penetrate the skin. We think that protective immunity against these worms may be dependent on interactions between nerve and immune cells in the skin, but this has not been studied before. The proposed experiments may also identify novel analgesic or anti-inflammatory compounds derived from these worms.

PI_NAMEs: HERBERT, DE'BROSKI R;ROSSI, HEATHER L (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Address;Affect;Afferent Neurons;Agonist;Analgesics;Anemia;Anti-Inflammatory Agents;Automobile Driving;Awareness;Bathing;behavioral outcome;behavioral response;Biological;Biological Models;Bone Marrow;Brain;Bypass;Calcium;Capsaicin;Case Study;Cations;Cell Communication;Cell Physiology;Cells;Chimera organism;Chronic;cytokine;Data;Dermal;Development;Disease;Dose;Epithelial Cells;Epithelium;Equation;experimental study;Exposure to;fast protein liquid chromatography;foot;gastrointestinal epithelium;gastrointestinal symptom;Goals;helminth infection;Helminths;Host resistance;Human;Immune;Immune response;Immunity;immunoregulation;Impairment;Infection;Inflammation;Inflammatory;Injections;insight;Invaded;keratinocyte;Knowledge;Larva;Lasers;Light;Mass Spectrum Analysis;Mediating;Methods;Modeling;Morbidity - disease rate;Mucous Membrane;multidisciplinary;Mus;Needles;Nematoda;Nerve;Neuroimmune;neuroimmunology;Neuromedin U;Neurons;Neuropeptides;neurotransmitter release;Nociceptors;novel;optogenetics;Pain;pain inhibition;pain perception;pain sensation;pain signal;Parasites;Parasitic infection;parasitism;pathogenic fungus;pathogenic microbe;Penetration;Perception;Persons;Population;prevent;Process;Proteins;Pruritus;recruit;release of sequestered calcium ion into cytoplasm;Resistance development;response;Rhodopsin;Role;Saline;secondary infection;Sensory;sensory neuroscience;Skin;skin damage;skin disorder;Soil;Stimulus;Strongyloides ratti;Strongyloides stercoralis;System;Techniques;Testing;Therapeutic;Tissues;Transgenic Mice;transmission process;TRPV channel;TRPV1 gene;Vanilloid;Wild Type Mouse;Withdrawal;Work

PROJECT_TITLE: Central role for skin sensory neurons in anti-helminth immunity

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


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

ORG_DEPT: NEUROLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Narrative The proposed research is relevant to public health because it will establish and validate a powerful new model to assay drugs or genetic targets that can treat the debilitating balance symptoms that define a neurodenera  tive disease. Therefore, the proposed research is relevant to the part of the NIH’s mission to develop scientific resources that will ensure the Nation’s capability to prevent and one day cure disease.

PI_NAMEs: BURTON, EDWARD ALAN;SCHOPPIK, DAVID  (contact)

PROGRAM_OFFICER_NAME: ROOF, REBECCA

PROJECT_TERMS: Address;appendage;Behavior;behavior test;Behavioral;Biochemical;Biological Assay;Biological Models;Brain;Brain Stem;Candidate Disease Gene;Cell Survival;cellular pathology;Chemical Modifier;Chemicals;Clinic;Clinical;Deglutition;Dementia;Deposition;design;Development;Diagnosis;Disease;disease prognosis;Disease Progression;Dissociation;effective therapy;Ensure;Equilibrium;Evaluation;Experimental Models;experimental study;Face;falls;Fracture;Functional disorder;Gene Targeting;Genetic;Hospitalization;Human;Impairment;improved;in vivo;Individual;innovation;Intervention;Label;Laboratories;Light;Limb structure;Link;MAPT gene;Measures;Mission;Modeling;Molecular;Molecular and Cellular Biology;molecular pathology;Monitor;Motor;Movement Disorders;Muscle;mutant;Nerve Degeneration;neural;neural circuit;Neurobiology;Neurodegenerative Disorders;neurodegenerative phenotype;Neurologic;Neurologic Deficit;Neurologic Symptoms;Neurologist;Neuronal Differentiation;neuronal patterning;Neurons;Neurophysiology - biologic function;novel;novel therapeutics;oculomotor;Ophthalmoplegia;Optics;Outcome;Pathologic;Pathology;Pharmaceutical Preparations;Phase;Phenotype;Physicians;Pilot Projects;Posture;posture instability;predictive test;prevent;programs;Progressive Supranuclear Palsy;Protein Isoforms;Protocols documentation;Public Health;Reagent;Reproducibility;Research;Resources;response;Scientist;Severities;skills;success;Symptoms;System;tau expression;tau mutation;tau Proteins;Tauopathies;Testing;Time;transgene expression;Transgenic Organisms;United States National Institutes of Health;Validation;Work;Zebrafish

PROJECT_TITLE: A Phenotype-Optimized Zebrafish Model of Progressive Supranuclear Palsy

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders B Study Section[NSD-B]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Rare Diseases;Sleep Research;Tuberous Sclerosis

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: NARRATIVE  Our internal biological clocks have a profound effect on many aspects of physiology and behavior including the sleep-wake cycle. Disruption of circadian rhythms causes sleep deficiency and puts people at higher risk of neurocognitive impairment. Our research focuses on a particular mechanism that links energy sensing in the cell with the circadian clock and how deregulation of this mechanism causes consequence in circadian, sleep and other neurophysiological functions.

PI_NAMEs: LIU, ANDREW C. (contact)

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: Address;Affect;Aggressive behavior;Alleles;anxiety-like behavior;autism spectrum disorder;Behavior;Behavioral;Benign;Biological Clocks;Biological Markers;Brain;brain dysfunction;Brain Neoplasms;Caregivers;Categories;cell growth;Cell model;Cells;Central Nervous System;Chronic;circadian;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Cognition;cognitive function;Data;Developmental Delay Disorders;Disease;Dose;Epilepsy;epileptiform;Fasting;feeding;Foundations;FRAP1 gene;Functional disorder;functional outcomes;Future;gain of function;Genes;Genetic;Genetic Diseases;genetic variant;Genotype;Goals;Growth;high risk;Homeostasis;Hyperactivity;Hyperphagia;Hypothalamic dysfunction;Impaired cognition;improved;improvement on sleep;inhibitor;insight;Intellectual functioning disability;Knock-in Mouse;Learning;Lentivirus;Link;Macrocephaly;Metabolic;Modeling;molecular clock;Motor Activity;mouse model;mTORopathies;Mus;Mutation;Nervous System Physiology;neurobehavior;Neurocognitive Deficit;neurophysiology;novel;Pathogenicity;Pathologic;Pathway interactions;Patients;Pattern;Persons;pharmacologic;Phase;Phenotype;Physiological;Physiology;precision medicine;proteostasis;Regimen;Regulation;Research;Role;Seizures;Sirolimus;Sleep;Sleep Deprivation;Sleep disturbances;Sleep Wake Cycle;Symptoms;Syndrome;System;Testing;Therapeutic Research;Time;Tissues;treatment strategy;TSC1 gene;Tuberous Sclerosis;Variant;variant of unknown significance

PROJECT_TITLE: Role of mTOR in Circadian and Sleep Deregulation in Smith-Kingsmore Syndrome (SKS)

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Nutrition;Orphan Drug;Rare Diseases

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: PROJECT NARRATIVE: Glioblastoma (GBM) is lethal brain tumor with a median survival of 15 months. Therefore novel therapy is urgently needed. Following analysis of data from The Cancer Genome Atlas, and subsequent experimental validation studies, we have identified a subgroup of GBM patients who can be treated with a novel combination of a specific drug and a research diet. We expect that our studies will shed new insights into a novel glioblastoma therapy.

PI_NAMEs: DASGUPTA, BIPLAB  (contact)

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: 1p36;Ablation;Acids;acquired drug resistance;Address;Algorithms;Alleles;Analytical Chemistry;Atlases;biological adaptation to stress;Biological Availability;Biological Markers;Biology;blood-brain barrier crossing;Brain Mass;Brain Neoplasms;cancer cell;Cancer Etiology;CDKN2A gene;cell growth;Cell Line;Cell Survival;Cells;Chromosome 10;chromosome 1p loss;Chromosomes;Classification;classification trees;Clinical Trials;Collaborations;Combined Modality Therapy;CRISPR/Cas technology;Culture Media;Custom;Data;Data Analyses;Data Set;Databases;Diet;Diet Research;Diet therapy;dietary;Dietary Component;Dose;Down-Regulation;driver mutation;drug sensitivity;efficacy evaluation;endoplasmic reticulum stress;enolase;Environmental Risk Factor;Enzyme Inhibitor Drugs;Enzymes;Epidermal Growth Factor Receptor;Etiology;Event;experience;experimental study;Fatty Acids;Feasibility Studies;FRAP1 gene;Gene Deletion;Genes;Genetic;Glioblastoma;Glioma;Goals;Growth;Human;Hypersensitivity;in vivo;inhibitor;inhibitor therapy;insight;Lesion;Lipids;loss of function;Malignant neoplasm of prostate;Malignant Neoplasms;Maximum Tolerated Dose;Medicine;Melanoma;Melanoma Cell;Membrane Fluidity;Messenger RNA;metabolomics;Methods;Methylation;Molecular;Monounsaturated Fatty Acids;mouse model;mTOR Inhibitor;Mus;Mutation;novel;novel therapeutics;Oleates;Oleic Acids;Oncogenes;Oral;overexpression;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Pharmacology;PI3K/AKT;PIK3CG gene;Plant Oils;Point Mutation;pre-clinical;preclinical study;Proliferating;Proteins;Proto-Oncogene Proteins c-akt;PTEN gene;Reducing diet;Refractory;Regimen;regression trees;Research;Residual state;Resistance;Resistance development;RNA Polymerase II;Signal Transduction;Specificity;statistics;Stearoyl-CoA Desaturase;stem cells;Stress;Subgroup;targeted cancer therapy;Testing;The Cancer Genome Atlas;Therapeutic;TP53 gene;treatment response;tumor;tumor growth;Tumor Suppressor Genes;Tumor Suppressor Proteins;Up-Regulation;Validation;validation studies

PROJECT_TITLE: Bystander gene deletions in cancer: mechanisms of therapeutic opportunities and challenges

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Digestive Diseases;Inflammatory Bowel Disease

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: We have found that a group of interferons (IFNs), named IFNλ, are critical for modulating inflammatory bowel diseases (IBDs) in both mice and humans yet can play opposing roles during the development and repair of disease, respectively. We found that IFNλ can dampen tissue damage by acting on neutrophils, but also decreases tissue repair by acting on intestinal epithelial cells. Employing both mouse and human model systems and patient-derived tissues, we propose to unveil the mechanistic basis for these activities, anticipating that these studies will be foundational for developing novel and effective therapeutic interventions against IBD.

PI_NAMEs: SNAPPER, SCOTT B;ZANONI, IVAN  (contact)

PROGRAM_OFFICER_NAME: PERRIN, PETER J

PROJECT_TERMS: Acute;Affect;Amphiregulin;Anti-viral Response;Apoptosis;Bacteria;Biochemical;Biological Models;Biopsy;Cell Death;Cell Line;cell type;Cells;Chronic;Colitis;COVID-19 patient;Critical Illness;Data;Defect;Development;Disease;early childhood;Enteral;Environment;Environmental Risk Factor;Epithelial Cells;Epithelium;Equilibrium;Etiology;Exposure to;Family;Flare;gastrointestinal epithelium;Gastrointestinal tract structure;Genes;Genetic;Genetic Transcription;Goals;healing;Homeostasis;Human;human model;human tissue;Immune response;Immune system;infancy;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory modulation;insight;Interferon Type I;Interferon Type II;Interferons;intestinal epithelium;Intestines;irradiation;Knowledge;Lamina Propria;Link;Lung;member;Mendelian disorder;microbial;microbial community;microbiota;Molecular;mouse model;Mucosal Immunity;Mucous Membrane;murine colitis;Mus;mutant;Mutation;Names;neutrophil;new therapeutic target;novel;novel therapeutic intervention;Organoids;Paneth Cells;Pathogenesis;Pathogenicity;Patients;Phase;Play;prevent;Production;programs;Proliferating;Property;Proteins;receptor expression;Receptor Signaling;Regulation;repaired;response;Role;Signal Transduction;Small Intestines;spatiotemporal;Stimulus;Surface;systemic inflammatory response;Therapeutic;Therapeutic Intervention;therapeutically effective;Time;tissue repair;Tissues;Variant;Viral;Viral Physiology;virome;Virus;Virus Diseases

PROJECT_TITLE: Type III interferon Control of Mucosal Immunity

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE Occupational exposure to manganese (Mn) through welding fumes continues to bear the risk of developing neurological impairments, with a safe exposure limit to airborne Mn being unknown. This study will define the dose-response relation of Mn deposition and elimination in the human brain, and investigate oxidative stress markers and neurotransmitter changes in a cohort of welders using personal air sampling and novel, non-invasive brain imaging techniques such as magnetic resonance imaging and spectroscopy. Understanding the spatial-temporal characteristics of human brain Mn deposition and neurochemical responses of the human brain will have significant translational impact on our understanding of the Mn dose-response relationship in welding, and will help defining a safe level of occupational exposure to Mn.

PI_NAMEs: DYDAK, ULRIKE  (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: air sampling;Aluminum;Aminobutyric Acids;Animals;Antioxidants;apprenticeship;Area;Basal Ganglia;Bayesian Analysis;Brain;Brain imaging;Brain Mapping;Brain region;career;Cells;Cerebellum;Chronic;Cognition;Cognitive;cognitive function;cohort;Data;Deposition;Diffusion;Dose;experience;Exposure to;frontal lobe;gamma-Aminobutyric Acid;Glutamates;Glutathione;Health;Human;Human Characteristics;imaging approach;imaging biomarker;imaging study;Imaging Techniques;Imaging technology;Impaired cognition;Impairment;Individual;Inhalation;innovation;Knowledge;Lead;Longitudinal Studies;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Manganese;Manufacturer;Maps;Measurement;Measures;Mediating;Mediation;Methods;Modeling;Moods;Motor;motor disorder;neurochemistry;neuroimaging;Neurologic;Neurological outcome;Neuropsychological Tests;neurotoxic;neurotoxicity;Neurotransmitters;novel;Occupational;Occupational Exposure;Occupations;Outcome;Oxidative Stress;Parkinson Disease;Parkinsonian Disorders;Phenotype;professional atmosphere;Protocols documentation;psychologic;recruit;Reduced Glutathione;Relaxation;Reporting;Research Design;response;Risk;Risk Factors;Schools;spatiotemporal;Spectrum Analysis;Substantia nigra structure;Symptoms;Techniques;Technology;Testing;Thalamic structure;Time;Toxic effect;Toxicokinetics;Translating;translational impact;uptake;Welding;white matter;Work

PROJECT_TITLE: Neuroimaging of Manganese Toxicity

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


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

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Anthrax is an acute infectious disease that affects both animals and humans with a high mortality rate. The proposed research is highly relevant to public health because the discovery of the molecular mechanisms of anthrax lethal toxin, the major virulence factor in anthrax infection, is critically important in order to develop potential therapeutics that could prevent anthrax-induced mortality. This application will develop the new concept of the reactivation/mobilization of toxin-disrupted pathways as a mechanistic-based targeted therapy.

PI_NAMEs: LIU, SHIHUI  (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, SUMAN

PROJECT_TERMS: Acute;Affect;Animals;Anthrax Attack;Anthrax disease;anthrax lethal factor;anti-toxin;Antibiotics;Antibodies;Bacillus anthracis;Bacterial Infections;Bioenergetics;Biological;Biological Process;Bioterrorism;c-myc Genes;Cardiac Myocytes;cardiovascular collapse;Cardiovascular system;Caring;Cell Proliferation;Cell Survival;Cells;Cessation of life;Clinical;Clinical Management;Communicable Diseases;Complement;Data;Death Rate;Disabling;Disease;Epidermal Growth Factor;evidence base;expectation;flu;Goals;Host Defense Mechanism;Human;Impairment;in vivo;Infection;Inhalation;lethal factor;MAP Kinase Gene;MAP2K1 gene;MAPK8 gene;Mediating;Medical;Medical Assistance;MEKs;Metabolism;Metalloproteases;Mitogens;Molecular;Molecular Target;mortality;mouse model;novel;Organ;p38 Mitogen Activated Protein Kinase;pathogen;Pathogenesis;Pathway interactions;Patients;Play;prevent;Public Health;repaired;Research;Resistance;resistance allele;Role;Septic Toxemia;Stress;Symptoms;targeted treatment;Testing;Therapeutic;Time;Tissues;Toxic effect;Toxin;Virulence Factors

PROJECT_TITLE: Mechanisms of anthrax lethal toxin-induced mortality and the novel biological-based targeted therapies

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Genetics;Health Effects of Indoor Air Pollution;Human Genome;Lead Poisoning;Mental Health;Neurosciences;Prevention;Social Determinants of Health

PHR: PROJECT NARRATIVE Early-life lead (Pb) exposures are known to result in pervasive effects on cognition and behavior that can persist across the lifespan, and, in some cases, across generations of descendants. There is increasing evidence linking developmental lead exposures, cognitive decline, and neurodegenerative disease risk in aged populations. The mechanistic underpinnings of these effects of toxicant exposure are unclear. Here, we seek to delineate how developmental lead exposure causes genetic and epigenetic changes that lead to adverse neurological health outcomes and transmit this public health issue over several generations.

PI_NAMEs: BAKER, TRACIE R (contact)

PROJECT_TERMS: Adult;aged;Aging;aging population;Air;Award;Behavior;Behavioral;Behavioral Assay;behavioral response;Biological Markers;Biological Process;blood lead;Brain;Brain region;Characteristics;Child;Chromatin;Cognition;Data;Development;diagnostic strategy;Disease;Disease Outcome;disorder risk;Dose;drinking water;Dust;Elderly;Embryo;Embryonic Development;Environment;Environmental Exposure;Epigenetic Process;epigenetic regulation;epigenome;epigenomics;evidence base;Exhibits;Exposure to;Gene Expression;Generations;Genes;Genetic;Genetic Processes;Genome;Genomics;Goals;HDAC4 gene;Health;Heritability;Histology;histone modification;Household;human old age (65+);Hyperactive behavior;Impaired cognition;Impairment;Investigation;Laboratories;late life;Lead;lead exposure;Lead levels;Lead Poisoning;Learning;Life;life span;Link;Mediating;Memory;Methods;Methylation;Modification;Molecular;Motor Activity;Mutation;National Institute of Environmental Health Sciences;Nervous System;Nervous System Physiology;neurobehavior;neurobehavioral;Neurodegenerative Disorders;neurodevelopment;neurogenesis;Neurologic;neurotoxic;Outcome;Paint;Pathway interactions;Phenotype;Predisposition;prevent;Prevention;Process;Public Health;Research;response;Risk Assessment;Route;Series;sex;Soil;Speech;Testing;Time;Toxic Environmental Substances;toxicant;Toxicant exposure;Toy;transcriptome;transcriptomics;Transgenic Organisms;transmission process;treatment strategy;United States;urban children;World Health Organization;Zebrafish

PROJECT_TITLE: Transcriptomic and epigenetic mechanisms of lead (Pb)-induced neurobehavioral disease in aged populations and subsequent generations


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative: Several neurodegenerative disorders are linked to lysosomal dysfunction whereby neurotoxic aggregates accumulate in and rupture lysosomes. Thus, neurons rely on lysosomal quality control mechanisms to rescue lysosomal membrane integrity or sequester damaged lysosomes via selective autophagy. The fundamental mechanisms activating the selective autophagy of lysosomes in neurons are unknown, and therefore, this proposal will investigate conserved mechanisms within lysosomal quality control, providing a groundwork for our understanding of lysosomal dysfunction in neurodegenerative disease.

PI_NAMEs: GALLAGHER, ELIZABETH RAYE (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Autophagocytosis;Autophagosome;Biogenesis;Biological Assay;Cell Death;Cells;Complex;Cytoprotection;Cytosol;cytotoxic;Data;density;Deubiquitinating Enzyme;Disease;Endosomes;Excision;experimental study;Functional disorder;Goals;Health;Hela Cells;Homo;Human;human induced pluripotent stem cells;immunocytochemistry;Immunoprecipitation;In Vitro;insight;knock-down;Link;link protein;Liquid substance;live cell imaging;Lysosomes;Measures;Mediating;Membrane;Microscopy;Monitor;mutant;Neurodegenerative Disorders;Neurons;neurotoxic;novel;Optics;Organelles;Parkinson Disease;Phase;Physical condensation;premature;prevent;Process;Proteins;Quality Control;receptor;Recombinants;reconstitution;reconstruction;recruit;Recycling;Regulation;repaired;Resistance;Role;Rupture;Signal Transduction;Small Interfering RNA;Sorting;Starvation;Stereotyping;superresolution microscopy;targeted treatment;Testing;Time;Ubiquitin;ubiquitin isopeptidase;Ubiquitination;Western Blotting

PROJECT_TITLE: Investigating mechanisms activating the selective autophagy of lysosomes


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: CHICAGO

PHR: PROJECT NARRATIVE Many solid tumors display a desmoplastic response characterized by an extensive deposition of collagen by cancer-associated fibroblasts (CAFs) which contributes to cancer progression and promotes therapy resistance. The proposed research will investigate the metabolic regulation of collagen production in CAFs. A better understanding of the unique metabolic requirements for CAF-mediated collagen production will help to identify targets to reduce tumor desmoplasia and thereby create novel therapeutic vulnerabilities.

PI_NAMEs: SCHWÖRER, SIMON  (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Acceleration;Advisory Committees;Affect;Amino Acids;Anabolism;Award;Bioenergetics;Biology;cancer cell;Cancer Model;Cancer Patient;Carbon;career;career development;cell type;chemotherapy;Citric Acid Cycle;Collaborations;Collagen;Communication;Data;Deposition;deprivation;Desmoplastic;Development;Development Plans;Educational process of instructing;Environment;experimental study;extracellular;Extracellular Matrix;Extracellular Matrix Proteins;Face;Faculty;Fibroblasts;Future;Glutamate Dehydrogenase;Glutamates;Glutamine;Goals;Grant;Hyperactivity;Impairment;improved;improved outcome;in vivo;Investigation;Knowledge;Laboratories;Laboratory Research;Malignant Neoplasms;Mediating;Memorial Sloan-Kettering Cancer Center;Mentors;Mentorship;Metabolic;metabolic abnormality assessment;Metabolism;metabolomics;Mitochondria;mouse model;Normal tissue morphology;novel;novel strategies;novel therapeutics;Nutrient;Outcome;oxidation;Oxidation-Reduction;Pancreatic Ductal Adenocarcinoma;Pathway interactions;Phase;Positioning Attribute;Production;Prognosis;programs;Proline;Proteins;Pyruvate;Pyruvate Carboxylase;Pyruvate Metabolism Pathway;Regulation;Reporting;Research;research and development;Research Personnel;Research Training;Resistance;response;Role;skills;Solid;Solid Neoplasm;Therapeutic;Tissues;Transfer RNA Aminoacylation;Translations;tumor;tumor metabolism;tumor progression;Tumor Promotion;Vascular blood supply;Vertebral column;Work;wound healing;Writing

PROJECT_TITLE: Investigating the metabolic regulation of tumor desmoplasia

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Transition to Independence Study Section (I)[NCI-I]


NIH_SPENDING_CATS: Bioengineering;Data Science;Networking and Information Technology R&D (NITRD)

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB

PHR: Project Narrative Basic biochemical mechanisms fundamental to human health arise from understanding the structure of large biological molecules, both proteins and nucleic acids. X-ray crystallography has been a key method for uncovering their function, and it continues to grow in importance as brighter X-ray sources and more sensitive detectors are developed. This is a computational technology project intended to provide a sharper picture than previously available, allowing some reactions to be followed with snapshots over time, and other experiments to avoid X-ray damage that would otherwise interfere with the measurement.

PI_NAMEs: SAUTER, NICHOLAS K (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: absorption;Accounting;Algorithms;Amino Acids;Bayesian Analysis;Big Data;Biochemical;Biochemical Reaction;Biological;Cellular Structures;Chemicals;Collaborations;Computer software;computerized data processing;Computing Methodologies;cost;Cryo-electron tomography;Crystallography;Data;Data Adjustments;Data Analyses;Data Collection;detector;Development;Diffuse;Electronics;Electrons;Environment;experimental study;flexibility;Funding;Gases;Genes;Geometry;Goals;Health;Heterogeneity;Human;improved;Incubated;Inherited;instrumentation;Lasers;Learning;Light;macromolecule;Measurement;metalloenzyme;Metals;Methods;Modality;Modeling;Molecular Conformation;molecular modeling;Monitor;Motion;Nucleic Acids;Organism;Oxidation-Reduction;Pattern;Physiologic pulse;Physiological;Process;Proteins;Pump;Radiation induced damage;Reaction;Regulation;Resolution;risk mitigation;Roentgen Rays;Role;Rotation;Sampling;Science;Site;small molecule;Source;spatiotemporal;Spottings;Structure;Structure-Activity Relationship;Supercomputing;Synchrotrons;Technology;Temperature;temperature jump;terabyte;Time;Water;X-Ray Crystallography;x-ray free-electron laser;Xray Emission Spectroscopy

PROJECT_TITLE: Cctbx.xfel:  Serial crystallography computational methods aimed at biomolecular function


PHR: Narrative Biofilms are communities of bacteria that adhere to one together and attach to surfaces; by virtue of growing in a biofilm, bacteria become highly resistant to antibiotics or immune responses and cause recurrent, hard-to- treat infections. In this project we will investigate the structure of key staphylococcal surface proteins and their interactions that hold bacterial cells together in the biofilm. The results from this research will provide new insights into controlling bacterial biofilm formation and reducing the risk of recurrent infections. 1

PI_NAMEs: HERR, ANDREW B (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Adhesions;Adhesives;Amyloid Fibrils;anti-microbial drug;Antibiotic Resistance;Bacteria;Biological;biophysical analysis;Cell Wall;Cells;Communities;Confocal Microscopy;design;Disease;Epidemic;Epithelial Cells;Genus staphylococcus;Goals;Growth;Immune response;Infection;insight;keratinocyte;Laboratories;Ligands;Liquid substance;mechanical properties;Mechanics;Mediating;Membrane Proteins;methicillin resistant Staphylococcus aureus;Microbial Biofilms;Molecular;Morphology;Nose;Orthologous Gene;Phase;polymicrobial biofilm;Predisposition;prevent;protein protein interaction;Proteins;Recurrence;recurrent infection;Research;Risk Reduction;Role;self assembly;Site;Spectrum Analysis;Staphylococcus aureus;Staphylococcus epidermidis;Structure;Surface;Therapeutic;Therapeutic Intervention;Virulence

PROJECT_TITLE: Structure and function of staphylococcal surface proteins involved in biofilm growth and virulence

STUDY_SECTION: MRAE

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - E Study Section[MRAE]


ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Project Narrative Autophagy plays an important role in animal health and development, and defects in this process are associated with a variety of human disorders including neurodegeneration, cancer and inflammatory diseases. We are investigating novel mechanisms that control cell context- specific regulation of autophagy during animal development, including cargo-specific autophagy pathways. The recent association of autophagy with multiple diseases, and interest in manipulating autophagy for therapeutic purposes, illustrates the importance of investigating the mechanisms that control cell context-specific regulation of autophagy.

PI_NAMEs: BAEHRECKE, ERIC H (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TITLE: Regulation of autophagy during animal development


ORG_CITY: CLEVELAND

ORG_DEPT: PATHOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Narrative Pyroptosis is a highly inflammatory form of cell death mediated by the gasdermin family members, and is implicated in infections and autoimmune or autoinflammatory disorders. This proposal will leverage our expertise in structural and biochemical studies of gasdermins and inflammatory caspases to investigate the post-translational regulation of gasdermins by proteases, ubiquitin ligases, palmitoyltransferases, and other enzymes. Better understanding of the mechanisms of gasdermin regulation is highly significant, which may stimulate the development of novel therapeutics that target pyroptosis and inflammation.

PI_NAMEs: XIAO, TSAN SAM (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Autoimmune Diseases;autoinflammatory diseases;Biochemical;Biology;Caspase;Cell Death;cytokine;Development;Enzymes;Family member;IL18 gene;Immune signaling;Infection;Inflammasome;Inflammation;Inflammatory;insight;Knowledge;Mediating;microbial;Modification;Molecular;new therapeutic target;Pathologic;Pathway interactions;Peptide Hydrolases;Physiological;Post-Translational Protein Processing;Post-Translational Regulation;programs;Regulation;Research;Signal Pathway;Structure;ubiquitin ligase;Ubiquitination

PROJECT_TITLE: Regulation of gasdermins through protease processing and other post-translational modifications.

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


NIH_SPENDING_CATS: Genetics;Human Genome;Neurosciences

ORG_CITY: NEW HAVEN

ORG_DEPT: NEUROSCIENCES

ORG_NAME: YALE UNIVERSITY

PHR: The precise regulation of mRNA translation, the process of protein synthesis carried out by the ribosome, plays an essential role in most biological functions. Our research focuses on understanding the role of mRNA translation control in the development and function of the nervous system, as well as how its dysregulation contributes to disease.

PI_NAMEs: GUO, JUNJIE  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Area;Biological Process;Data;Development;Disease;Elements;genome-wide analysis;Goals;human disease;Initiator Codon;Investigation;Mammalian Cell;Measurement;Measures;Messenger RNA;Metabolism;Microsatellite Repeats;mRNA Translation;Nervous System;Nervous System Physiology;neuronal pentraxin receptor;Neurons;Play;Post-Transcriptional Regulation;posttranscriptional;Procedures;Process;Protein Biosynthesis;Regulation;Research;ribosome profiling;Ribosomes;RNA;Role;transcriptome;Translation Initiation;Translations;Work

PROJECT_TITLE: Post-transcriptional mRNA regulation in the mammalian nervous system

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MRAF-C (01)]


NIH_SPENDING_CATS: Bioengineering;Networking and Information Technology R&D (NITRD)

ORG_DEPT: CHEMISTRY

PHR: Project Narrative  Lack of robust and selective methods for the synthesis of structurally diverse organic molecules is a major bottleneck in the drug discovery process. This proposal aims to address this general challenge by developing and applying computational tools to guide experimental development of transition metal and enzyme-catalyzed reactions to selectively functionalize alkenes.

PI_NAMEs: LIU, PENG  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Active Sites;Address;Alkenes;Biomedical Research;Catalysis;catalyst;Collaborations;Complex;Computer Models;computer studies;computerized tools;density;design;Development;drug discovery;Engineering;Enzymes;experimental group;flexibility;Goals;improved;innovation;insight;Mediating;Methods;Modeling;Molecular Conformation;molecular dynamics;Nature;Pathway interactions;predictive modeling;Process;programs;Reaction;Research;Role;screening;Series;Solvents;Substrate Interaction;System;theories;Transition Elements

PROJECT_TITLE: Computational Models for Reactivity and Selectivity in Catalytic Olefin Functionalization


NIH_SPENDING_CATS: Biotechnology;Genetics;Machine Learning and Artificial Intelligence

PHR: We will characterize the cellular mechanism(s) of endosomal membrane damage and repair, which we can now observe directly, to relate these mechanisms to delivery of cargo into the cytosol. This understanding will facilitate development of strategies for enhancing delivery of biological therapeutics into targeted cells.

PI_NAMEs: KIRCHHAUSEN, TOMAS  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: 3-Dimensional;adaptive optics;alpha synuclein;Antisense Oligonucleotides;Biological Response Modifier Therapy;Cells;Cellular biology;Clathrin;Color;Cytosol;Data Set;deep learning;Detection;Development;Endocytosis;endosome membrane;Endosomes;Event;Goals;imaging modality;Light;Link;Lipopolysaccharides;Liquid substance;Lysosomes;Mediating;MicroRNAs;Microscopy;movie;novel;Phase;prevent;repaired;Route;Small Interfering RNA;Three-Dimensional Imaging;uptake;Work

PROJECT_TITLE: Cell Biology of Endosomal Escape

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


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

ORG_CITY: BLOOMINGTON

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

PHR: Project Narrative This proposal outlined research to dissect the mechanisms of the evolutionarily conserved homologous recombination pathway in DNA damage repair. Defects in homologous recombination cause a high risk of cancer with breast and ovarian cancer in particular. Hence, the knowledge acquired from our research endeavor will shed light on both the tumorigenesis and cancer treatment.

PI_NAMEs: NIU, HENGYAO  (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: cancer therapy;Cells;Chromosome Breakage;Chromosome Segregation;Defect;Digestion;Dimerization;DNA biosynthesis;DNA Double Strand Break;DNA lesion;DNA Repair;Double Strand Break Repair;Excision;Genome;helicase;High-Risk Cancer;homologous recombination;Human;Knowledge acquisition;Laboratories;Maintenance;Malignant Breast Neoplasm;Malignant neoplasm of ovary;mutant;novel;nuclease;Pathway interactions;Regulation;repaired;Research;Role;Single-Stranded DNA;SS DNA BP;tool;tumorigenesis;Work;Yeasts

PROJECT_TITLE: Mechanism and Regulation of Homologous Recombination in Genome Maintenance


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

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative The efforts of my research program have been directed at probing the actions of membrane receptors and their G protein signaling partners that influence cell growth, differentiation, and development. These studies have culminated in a series of exciting new discoveries that describe how these signal transduction pathways are linked to the assembly of multi-protein complexes that regulate the metabolic activities of cells and the biogenesis of extracellular vesicles, important in embryonic stem cell function, differentiation, cellular senescence and aging, cancer, and infectious disease. By probing the signaling mechanisms that regulate these metabolic complexes and the biogenesis and function of extracellular vesicles, together with elucidating their structural features, we expect to gain new insights into the critical roles they play in a broad spectrum of biology and disease, as well as highlight new targets and strategies for therapeutic intervention.

PI_NAMEs: CERIONE, RICHARD A. (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Address;Area;Bacteria;Biochemical;Biogenesis;Biological Process;Biology;cancer cell;cancer survival;cdc42 GTP-Binding Protein;Cell Aging;cell growth;cell growth regulation;cell motility;Cell Physiology;Cell Polarity;Cell Survival;Cells;Cellular biology;Cloning;Communicable Diseases;Complex;Cues;Development;Disease;embryonic stem cell;Environment;Epidermal Growth Factor Receptor;Evolution;extracellular vesicles;FRAP1 gene;genetic regulatory protein;Glutamine;Goals;GTP-Binding Proteins;Human;insight;intercellular communication;interdisciplinary approach;Knowledge;Laboratories;Link;Malignant Neoplasms;Mediating;Membrane;Messenger RNA;Metabolic;Metabolism;Monomeric GTP-Binding Proteins;Multiprotein Complexes;Neuronal Differentiation;novel;Organism;Physiology;Play;Process;programs;protein complex;Protein Kinase;receptor;Regulation;Research;RNA Splicing;Role;Series;Signal Transduction;Signal Transduction Pathway;Signaling Protein;stem cell function;Therapeutic Intervention;three dimensional structure;Up-Regulation;Yeasts

PROJECT_TITLE: Studies of Global Signal Transduction


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: ANN ARBOR

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: The proposed research will lead to new fundamental insights into how the active transport and positioning of essential cellular cargos in bacteria are spatiotemporally driven and coordinated with each other and the cell cycle. The research also lays the groundwork for exploring therapeutic avenues aimed at disrupting the spatial organization of cellular cargos associated with bacterial pathogenicity. Finally, this work will generate the necessary fundamental knowledge for engineering transport systems for protein-based organelles for synthetic biology and biomedical applications, such as the biological production of drugs, drug delivery, and bioimaging.

PI_NAMEs: VECCHIARELLI, ANTHONY G (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Active Biological Transport;Adaptor Signaling Protein;Antibiotics;ATP phosphohydrolase;Bacteria;bioimaging;Biological;Cell Cycle;Cell division;Cells;Chemotaxis;Chromosome Segregation;Chromosomes;Creativeness;Data;Dedications;design;Disparate;Drug Delivery Systems;drug production;Engineering;Eukaryotic Cell;Family;field study;Flagella;Genetic;Goals;Health;Human;human pathogen;insight;Knowledge;link protein;Mind;Modeling;Motor;novel;Organelles;Organism;Pathogenesis;pathogenic bacteria;Pathogenicity;Positioning Attribute;Proteins;Reaction;Research;spatiotemporal;Specificity;synthetic biology;System;Therapeutic;Thiobacillus neapolitanus;trafficking;Variant;Work

PROJECT_TITLE: Coordinated Spatial Organization in Bacteria

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


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: Columbus

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative Dramatic changes in glucose metabolism-associated O-GlcNAc signaling occur in response to pathogen infection. Based on my preliminary results, I aim to study the role and mechanism of the O-GlcNAc transferase in mounting host defense response against viral and bacterial challenge. Dissecting the enzyme activity- dependent and -independent function of OGT in host defense mechanism will be instrumental for the generation of new strategies targeting the prevention and/or treatment of infectious diseases.

PI_NAMEs: WEN, HAITAO  (contact)

PROJECT_TERMS: Affect;Bacteria;Cell model;Cell Physiology;defense response;Detection;Development;Diabetes Mellitus;Disease;enzyme activity;Enzymes;Fatty Acids;Gene Deletion;Generations;glucose metabolism;Goals;Health;Host Defense;Host Defense Mechanism;human disease;Immune;immune activation;Immune signaling;immunoregulation;Individual;Infection;infectious disease treatment;Inflammation;Innate Immune Response;Invaded;Knowledge;lipid metabolism;Malignant Neoplasms;Mediating;Metabolic;Metabolic Pathway;Metabolism;Modeling;Molecular;mouse model;Neurodegenerative Disorders;Nuclear Proteins;O-GlcNAc transferase;pathogen;Pathway interactions;Physiological;Play;Post-Translational Protein Processing;Prevention;Proteins;Regulation;Research;response;Role;septic;Signal Transduction;Ubiquitination;Viral;Virus;Virus Diseases;Virus Integration;Work

PROJECT_TITLE: Essential functions of OGT in host defense mechanism