FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Child Abuse and Neglect Research;Clinical Research;Pediatric;Prevention;Social Determinants of Health;Violence Research;Youth Violence

ORG_CITY: TEMPE

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: PROJECT NARRATIVE  Youth placed in out-of-home care engage in more health risk behaviors, such as substance use and sexual risk behavior, and this risk may be heightened among youth placed during adolescence. However, few studies have tested the short-term and long-term effects of out-of-home placement in adolescence on health risk behavior or examined mechanisms underlying these effects, and no studies have used methods for causal inference that can accommodate the time-varying nature of the variables in these models. The proposed study uses modern quantitative methods for causal inference to test the direct and mediated effects of out-of-home placement on later health risk behaviors among maltreated adolescents, providing important implications for child welfare policy and prevention of health risk behaviors among vulnerable youth.

PI_NAMEs: BLAKE, AUSTIN  (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: Address;Adolescence;Adolescent;Adult;Age;Behavior;Biological;career;Caregivers;Caring;Child;Child Abuse and Neglect;Child Welfare;Childhood;Development;Environment;Event;experience;Exposure to;Family;Fellowship;Financial cost;foster care;Foundations;Health;Health Status;high risk;Home;Individual;Intervention;Long-Term Effects;maltreatment;Mediating;Mediator;Mentors;Methods;Modeling;Modernization;multidisciplinary;Nature;Outcome;Parents;patient home care;Personal Satisfaction;Policies;Population;Prevention;preventive intervention;Probability;Psychopathology;Research;Risk;Risk Behaviors;Risk Factors;Safety;Sampling;Schools;Scientist;Scoring Method;Selection Bias;Services;Sex Behavior;sexual risk behavior;societal costs;Substance Addiction;substance use;Surveys;Symptoms;systems research;Testing;therapy design;Time;Training;Unsafe Sex;young adult;Youth

PROJECT_TITLE: Estimating the Impact of Out-of-Home Placement on Health Risk Behavior in Adolescents Exposed to Maltreatment: An Advanced Causal Inference Approach

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F16-L(20)L]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Climate-Related Exposures and Conditions;Emerging Infectious Diseases;Infectious Diseases;Machine Learning and Artificial Intelligence;Prevention;Rare Diseases;Vector-Borne Diseases

ORG_CITY: COLUMBIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

ORG_STATE: SC

PHR: Project Narrative Mosquito-borne diseases are a global concern that impact public health, tourism, and natural disaster recovery efforts. With no preventative vaccines or effective therapeutic option available for most mosquito-borne diseases, vector control efforts are the only combative option; however, these efforts are often limited by financial constraint and insecticide resistance concern. This proposed project aims to integrate cutting-edge mosquito collection traps, and novel remote sensing and machine learning workflows to guide local vector operations and direct abatement efforts in a cost-efficient manner.

PI_NAMEs: GUNTER, SARAH MURPHY;NOLAN, MELISSA SUZANNE (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Abate;Aedes;Algorithms;Aptitude;arboviral disease;Arbovirus Infections;Arboviruses;Area;Artificial Intelligence;atmospheric sciences;Bite;Breeding;Budgets;Cessation of life;Characteristics;chikungunya;Chikungunya virus;Cities;Climate;climate change;Clinical;Collection;combat;Comparative Study;Competence;Complex;Compost;cost;cost efficient;Culicidae;Data;data standards;Decision Making;Dengue;Dengue Virus;Detection;Development;Discipline;Disease;Disease Outbreaks;Ecology;Economics;Environment;Environmental Health;Environmental Impact;Epidemic;Evaluation;Event;Eye;Food;Gases;Geography;Gravid;Growth;Habitats;Health;Health Benefit;high risk;Household;Human;Human Bites;Image Analysis;Imagery;Impairment;improved;indexing;Individual;Industry;Infrastructure;innovation;Insecticide Resistance;Insecticides;Intervention;Lasers;Life;Location;Machine Learning;machine learning model;Manuals;Maps;meteorological data;Methods;metropolitan;Microclimate;Mosquito Control;Mosquito-borne infectious disease;Natural Disasters;Neighborhoods;Neurologic;next generation;novel;Oils;operation;Outcome;pathogen;Pattern;Persons;Pilot Projects;Population;predictive modeling;predictive signature;preference;preservation;Prevention;Preventive vaccine;Process;programs;prospective;Protocols documentation;Public Health;rapid detection;Reaction;Recovery;remote sensing;Reproducibility;Resolution;Resources;Risk;Robotics;scientific atmosphere;Seasons;Security;Sentinel;Side;Site;Solid;Sorting;spectrograph;Surveillance Methods;System;Techniques;Technology;Testing;therapeutically effective;Time;tool;Toy;transmission process;United States National Aeronautics and Space Administration;vector;vector control;Visualization;wasting;Weather;weather patterns;ZIKA;Zika Virus

PROJECT_TITLE: Next generation mosquito control through technology-driven trap development and artificial intelligence guided detection of mosquito breeding habitats

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Eating Disorders;Mental Health;Mental Illness;Nutrition

ORG_CITY: PHILADELPHIA

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE Self-help cognitive behavior therapies (CBTs) for binge eating are maximally effective when paired with periodic contact with expert clinicians. Clinicians likely improve outcomes because they are trained to utilize specific behavior change techniques for facilitating treatment adherence and skills utilization during self-help CBT program. Given the limited availability of expert clinicians, it is critical to understand how to enhance outcomes from self-help CBTs without clinician involvement. Technological innovations such as Advanced Digital Data Sharing with Coaches and Just-in-time adaptive interventions (JITAIs) can potentially emulate some of the behavior change techniques used by expert clinicians and improve treatment targets. The proposed study will use a full factorial design, in which 76 individuals with transdiagnostic binge eating will be assigned to one of 4 treatment conditions, i.e., representing each permutation of two intervention factors (Advanced Digital Data Sharing with Coaches, and JITAIs) hypothesized to improve treatment adherence and skills utilization being included or excluded from a base self-help CBT program (delivered via a website and companion smartphone application) without clinician involvement.

PI_NAMEs: HAGERMAN, CHARLOTTE  (contact)

PROGRAM_OFFICER_NAME: HAIM, ADAM J

PROJECT_TERMS: Abstinence;acceptability and feasibility;adaptive intervention;Aftercare;Algorithms;Area;Bachelor's Degree;base;Behavior;behavior change;Behavior Disorders;Behavioral;Binge Eating;Books;Cellular Phone;Clinical;Cognitive Therapy;Companions;cost effective;Data;data sharing;design;Development;Diagnostic;digital data;digital monitoring;discrete time;Disease;Eating;Eating Disorders;efficacy evaluation;Electronic Mail;Electronics;Evidence based program;Exclusion;feasibility testing;Feedback;follow-up;Food;Frequencies;Health;Healthcare Systems;improved;improved outcome;Individual;Intervention;Meta-Analysis;Monitor;Outcome;Pathway interactions;Patients;Pattern;Periodicals;programs;Recommendation;Recurrence;Self Administration;Self Direction;self help;skills;smartphone application;System;Techniques;technological innovation;Technology;technology intervention;Testing;Therapeutic;therapy design;Time;Training;treatment adherence;Treatment outcome;treatment program;Validation;web site

PROJECT_TITLE: Using factorial design to examine efficacies of technology-based augmentations for improving treatment adherence and skills utilization in a self-help CBT program for binge eating.


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: NEW YORK

ORG_DEPT: CHEMISTRY

ORG_NAME: NEW YORK UNIVERSITY

ORG_STATE: NY

PHR: Project Narrative Conversion of ubiquitous C–H bonds to C–heteroatom bonds could provide expeditious access to medicinally relevant molecules; however, current methods often require the use of endangered transition-metals, expensive enzymes, and/or harsh oxidants. The strategy proposed offers a sustainable solution by utilizing economical photoexcited nitroarenes that serve as the C–H bond activator and the oxygen atom source to enable novel C– H hydroxylation events anaerobically. Strategies for C–X and C–N bond formation at the expense of C–H bonds via interception of the in-situ formed hydroxylation intermediate under these mild and operationally simple conditions can lead to a universal platform for the incorporation of heteroatoms into organic molecules.

PI_NAMEs: PARASRAM, MARVIN  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: MIRA: C(sp3)-H Heteroatom Incorporation Using Photoexcited Nitroarenes


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

ORG_CITY: NEW HAVEN

ORG_DEPT: PHYSICS

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE The proposed research is relevant to the part of NIGMS’s mission seeking fundamental knowledge relevant to treating human disease because it will investigate the physical basis and functional consequences of phase separated domains in the membrane and cytoplasm. Understanding these domains could transform our understanding of neurodegenerative and other diseases which often involve pathological aggregation and other aberrant domain formation. It could also transform our understanding of a wide variety of drugs and treatments including alcohol and some anesthetics which alter domain formation.

PI_NAMEs: MACHTA, BENJAMIN BROOKS (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Alcohols;analog;Anesthetics;Automobile Driving;Behavior;Binding;Biological;Biological Process;Cells;Cellular biology;Cytoplasm;digital;Disease;Environment;experimental study;Grain;Heterogeneity;high dimensionality;human disease;Individual;insight;Ion Channel;Kinetics;Knowledge;Label;Laboratories;lipidomics;Lipids;Literature;Membrane;Mission;Modeling;molecular dynamics;National Institute of General Medical Sciences;Nerve Degeneration;Nucleic Acids;Pathologic;Pharmaceutical Preparations;Phase;Physics;Play;Process;Proteins;Regulation;Research;Research Personnel;Role;Shapes;Signal Transduction;simulation;Solid;Structure;Surface;Synapses;Systems Biology;Techniques;theories;Thermodynamics;Transcriptional Regulation;Work

PROJECT_TITLE: Physics and Systems Biology of Cellular Domains

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


ADMINISTERING_IC: EB

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Nanotechnology;Neurosciences;Rare Diseases

ORG_CITY: PROVO

ORG_NAME: BRIGHAM YOUNG UNIVERSITY

ORG_STATE: UT

PHR: Project Narrative Fatal or impairing neurological diseases, including movement disorders, brain cancers, psychological disorders, epilepsies, malformations, and memory disorders, impose heavy burdens on both individuals and society at large. Transcranial magnetic resonance guided focused ultrasound surgery (tMRgFUS) is an extremely promising, minimally invasive treatment modality for neurological diseases whereby sound waves are focused to a specific region of the brain and elicit a number of beneficial effects such as heating, immune-modulation, neuromodulation, and blood-brain-barrier disruption. Our experience has identified an opportunity to improve the treatment efficacy of tMRgFUS by resolving a ubiquitous impediment to accurate and information-rich guidance imaging: the acoustic coupling medium. This study will develop and validate a new acoustic coupling medium that promotes more accurate and information-rich guidance during tMRgFUS.

PI_NAMEs: ALLEN, STEVEN P (contact)

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: Acceleration;Acoustics;Affect;Alzheimer's Disease;aqueous;Bathing;biomaterial compatibility;Blood coagulation;blood-brain barrier disruption;Brain region;Cephalic;Chemistry;Clinical;clinical translation;Compensation;Coupling;decay acceleration;design;Development;Disease;Engineering;Epilepsy;Essential Tremor;experience;FDA approved;Feedback;fluid flow;Focused Ultrasound;Future;Gases;Glioblastoma;Heating;human subject;Image;image guided;Imaging Techniques;immunoregulation;Impairment;improved;improved outcome;Individual;Iron;iron oxide nanoparticle;Liquid substance;Literature;Magnetic Resonance;Magnetic Resonance Imaging;malformation;Malignant neoplasm of brain;Measures;Memory Disorders;Mental disorders;Methods;minimally invasive;Modality;Morbidity - disease rate;Morphologic artifacts;Motion;Movement Disorders;MRI Scans;nanoparticle;Nervous System Disorder;Neurologic;neuroregulation;novel;Operative Surgical Procedures;Parkinson Disease;particle;Patients;Play;Process;Property;Reporting;Research;Role;Science;Signal Transduction;Societies;sound;Surface;Suspensions;Techniques;Technology;Temperature;Testing;Time;Tissues;Transducers;Translations;transmission process;Treatment Efficacy;Tremor;tumor;ultrasound;Unconscious State;vibration;Water;Work

PROJECT_TITLE: Iron Based Coupling Media (IBCM) for MRI-guided Transcranial Ultrasound Surgeries

STUDY_SECTION: IGIS

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


ADMINISTERING_IC: AA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Pediatric;Recovery Support Services;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: The career development plan includes training in alcohol-specific recovery processes and trajectories of change, social identity and social network change processes for recovery during adolescence, social network and mixed methods study design, and lab management and grantsmanship. The K01 study is a longitudinal observational study that will utilize a social identity mapping (SIM) approach to examine social network, social identity, and recovery capital change among adolescents with AUDs in outpatient treatment. The SIM will be adapted from existing adult implementation models to specifically address adolescent needs and a comprehensive longitudinal model of the effects of adolescents' social network, social identity, and recovery capital on substance use outcomes will be developed.

PI_NAMEs: HENNESSY, EMILY A (contact)

PROGRAM_OFFICER_NAME: HAGMAN, BRETT THOMAS

PROJECT_TERMS: Abstinence;Address;Adolescence;Adolescent;adolescent health;adolescents with alcohol use disorders;Adult;Affect;Alcohol consumption;alcohol use disorder;Alcohols;Ambulatory Care;Area;Behavior;behavior change;Behavioral Mechanisms;Brain;burden of illness;Capital;career development;Communities;Coping Skills;Data;Data Collection;Data Set;Development;Development Plans;Educational workshop;emerging adult;Ensure;Equation;Evaluation;Exercise;experience;Family;Focus Groups;Friends;Health behavior;Human;Impairment;improved;Individual;International;Journals;Knowledge;Lead;Longitudinal, observational study;Maintenance;Manuscripts;Maps;meetings;member;Mentored Research Scientist Development Award;Mentors;Methods;Modeling;mortality;Motivation;novel strategies;Occupations;Outcome;Participant;Pathway interactions;Pattern;peer;Peer Group;Peer Review;Process;programs;Protocols documentation;Publications;Quality of life;Questionnaires;Recording of previous events;Recovery;Recovery Support;recruit;reduced substance use;Research;Research Activity;Research Design;research study;Resources;return to use;Review Literature;Risk Behaviors;Role;Sampling;Scientist;secondary analysis;Series;sex;Shapes;Site;skills;skills training;sobriety;social;social attachment;Social Change;Social Environment;social group;Social Identification;social influence;Social Network;Social Processes;Structure;substance use;substance user;Surveys;sustained recovery;symposium;Symptoms;systematic review;Testing;Time;Training;treatment site;visual map;Writing;Youth

PROJECT_TITLE: Mechanisms of social identity, social networks, and recovery capital: Implicationsfor recovery


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Bioengineering;Cancer;Cardiovascular;Digestive Diseases;Esophageal Cancer;Heart Disease;Orphan Drug;Physical Injury - Accidents and Adverse Effects;Precision Medicine;Prevention;Radiation Oncology;Rare Diseases

ORG_CITY: POTOMAC

ORG_NAME: NELSON SCIENTIFIC LABS LLC

ORG_STATE: MD

PHR: Project Narrative There is a need for minimally invasive, cost-effective and high-throughput methods to identify individuals who survive high radiation doses from a radiological event, but are subsequently at risk of developing radiation induced tissue/organ injuries. We propose to validate the CardioWatch panel predictive of radiation cardiac injury. The long-term goal of this work is to design a kit-based biomarker assay that can be used to estimate risk and severity of late radiation injuries in victims of a radiological event before the appearance of clinical symptoms.

PI_NAMEs: KANHOLM, TOMAS  (contact)

PROGRAM_OFFICER_NAME: RIOS, CARMEN I

PROJECT_TERMS: Acute;acute toxicity;Adult women;Advanced Development;Affect;Aftercare;Algorithmic Analysis;Algorithmic Software;Appearance;atomic bomb;biodosimetry;Biological;Biological Assay;Biological Markers;Biological Models;biomarker development;biomarker panel;Blinded;Blood;Cancer Patient;Cardiac;Cardiovascular Diseases;Cause of Death;Characteristics;Chest;Clinical;clinical research site;cohort;commercialization;Companions;coronary fibrosis;Correlative Study;cost effective;Data;design;Development;Diagnostic Reagent Kits;Dose;Early identification;Echocardiography;Ensure;esophageal cancer patient;evaluation/testing;Exhibits;Exposure to;Funding;Future;Gamma Rays;Goals;graphical user interface;Guidelines;Heart;Heart Diseases;heart function;Heart Injuries;Histologic;Inbreeding;Individual;Injury;insight;interest;Intervention;Ionizing radiation;irradiation;Japanese;Kidney;Late Effects;Late Radiation Injury;Leg;Legal patent;Licensing;Lipids;Liquid Chromatography;male;Malignant neoplasm of esophagus;manufacture;Marketing;Mass Spectrum Analysis;Measurement;Measures;medical countermeasure;Methods;minimally invasive;Modeling;Molecular;Monitor;Morbidity - disease rate;mortality;mouse model;multiple omics;multiple reaction monitoring;Mus;National Institute of Allergy and Infectious Disease;nonhuman primate;Nuclear;organ injury;Organ Specificity;Outcome;Patients;Performance;Pericardial effusion;Phase;phase 2 study;Plasma;potential biomarker;predictive panel;predictive test;Predisposition;Procedures;programs;Proteins;Qualifying;Quality of life;Radiation;Radiation Accidents;radiation countermeasure;Radiation Dose Unit;Radiation exposure;Radiation Injuries;radiation response;Radiation therapy;Radiation Toxicity;Rat Strains;Rattus;Reporting;Reproducibility;research clinical testing;Resolution;Risk;Risk Assessment;Risk Estimate;risk prediction;Rodent;Roentgen Rays;Sampling;screening;Serum;Severities;Small Business Innovation Research Grant;Software Tools;Source;Specificity;Sprague-Dawley Rats;Structure of parenchyma of lung;success;Survivors;Symptoms;Terrorism;Testing;Time;Tissues;University Hospitals;Validation;validation studies;Work

PROJECT_TITLE: CardioWatch: An Omics-Based Prediction Assay for Cardiac Late Effects ofAcute Radiation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CTH-E(11)B]


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: DALLAS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative We will systematically explore epistatic interactions that drive evolution of antibiotic resistance with the ultimate goal of developing novel antibiotics and antibiotic treatment strategies that select against resistance. Towards this goal, we will study molecular evolution of the dihydrofolate reductase (DHFR) enzyme in Escherichia coli under antibiotic selection, and engineer mutant-specific competitive and allosteric DHFR inhibitors that can select against resistance-conferring DHFR mutations. Finally, we will develop and synthesize a novel class of molecules that we named “-lactamase traps” (or BLTs) to select against -lactamase genes in Gram-negative bacteria.

PI_NAMEs: TOPRAK, ERDAL  (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Anti-Bacterial Agents;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Bacteria;Bacterial Antibiotic Resistance;beta-Lactam Resistance;beta-Lactamase;beta-Lactams;Biochemical;Biological Assay;Biological Sciences;Carbapenems;Cephalosporinase;Cephalosporins;Chemicals;Clinic;Clinical;Communicable Diseases;Cyclophosphamide;design;Dihydrofolate Reductase;Dihydrofolate Reductase Inhibitor;DNA Gyrase;Drug Targeting;effective therapy;Engineering;Enzymes;Escherichia coli;Evolution;FDA approved;fitness;Folic Acid;Future;Genes;Genetic;Genetic Epistasis;Genotype;Goals;Gram-Negative Bacteria;Health;Hydrolysis;In Vitro;Induced Mutation;inhibitor;innovation;Interdisciplinary Study;Lactamase;Lactams;Libraries;Life;Maps;Mathematics;Metabolism;Modeling;Modification;Molecular Evolution;Monobactams;Mutagenesis;mutant;Mutation;Names;Non-Steroidal Anti-Inflammatory Agents;novel;novel drug class;Operative Surgical Procedures;Pathway interactions;Patient-Focused Outcomes;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Procedures;Prodrugs;programs;Public Health;Research;Resistance;resistance mechanism;Role;Shapes;Site;small molecule;Testing;therapeutic target;Time;tool;treatment strategy;Trimethoprim;Trimethoprim Resistance;Variant

PROJECT_TITLE: Mapping epistatic interactions in molecular evolution of antibiotic resistance

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

ORG_STATE: CA

PHR: PROJECT NARRATIVE The overall objective of this proposal is to develop a workplan for investigating biophysical dynamics of PROTAC interactions by the combination of in silico modeling and in vitro assay screening. The research aims to identify structural features that lead to stable ternary complex formation of drug candidates. The results will provide molecular basis and a technical platform for effective search of therapeutics with a PROTAC strategy.

PI_NAMEs: CHENG, QUAN JASON (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Affect;Affinity;anaplastic lymphoma kinase;Attention;Back;Binding;Binding Proteins;Biological Assay;Biomedical Research;Biomimetics;Biophysics;Cell membrane;Cells;Complex;Computer Models;design;Disease;Dose;drug candidate;drug development;Drug resistance;Drug Targeting;Environment;Excision;experience;experimental study;fabrication;Goals;in silico;In Vitro;in vitro Assay;inhibitor;innovation;insight;interest;Investigation;Knowledge;Label;Left;Ligands;Lipids;Lysosomes;Malignant Neoplasms;Measurement;Membrane;Membrane Lipids;Methodology;Modality;Modeling;Molecular;molecular modeling;molecular recognition;multicatalytic endopeptidase complex;Mutagenesis;novel drug class;Property;Protac;protein degradation;Protein Dynamics;Proteins;Receptor Protein-Tyrosine Kinases;Reporting;Research;Role;screening;side effect;small molecule;stem;Structure;Structure-Activity Relationship;Surface Plasmon Resonance;System;Technology;Theoretical model;Therapeutic;Thinness;ubiquitin-protein ligase;Ubiquitination;Work

PROJECT_TITLE: Rational PROTAC design enabled by integrated in silico molecular modeling and in vitro biomimetic affinity assessment

STUDY_SECTION: MSFA

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


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Genetics;Health Services;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Cancer;Liver Disease;Prevention;Rare Diseases

ORG_CITY: LAGOS

ORG_COUNTRY: NIGERIA

ORG_FIPS: NI

ORG_NAME: COLLEGE OF MEDICINE, UNIVERSITY OF LAGOS

PHR: Project Narrative It is proposed in this application that the use of a minimally invasive quantitative molecular based mitochondrial DNA content of Peripheral Blood Mononuclear Cells (PBMC) as diagnostic biomarker to screen chronic hepatitis B (CHB) infected persons in Nigeria will promote early detection of hepatocellular carcinoma (HCC), minimize hazards and cost of investigation. I will leverage on the access provided by the K43 career development award to effectively utilize resources for the proposed research and training activities as well as the support and guidance provided by my mentors and co-mentors in US, India, and Nigeria for the needed enablement to transition to an independent researcher and translate the research outcomes to beneficial public health policy and practice.

PI_NAMEs: ADISA, RAHMAT ADETUTU (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Ablation;Accreditation;Advocate;Africa;Africa South of the Sahara;Age;aged;Alcohol consumption;arm;Award;Base Pairing;bench to bedside;Biological Markers;Biopsy;Blood specimen;Blood Vessels;career development;Chronic Hepatitis B;Clinic;Clinical Research;Cohort Studies;comparative;Competence;Contracts;cost;Data;data management;Detection;detection method;Diagnosis;Diagnostic;diagnostic accuracy;diagnostic biomarker;Diagnostic Procedure;Diagnostic tests;early detection biomarkers;Early Diagnosis;Early identification;early screening;effectiveness evaluation;Enrollment;experience;Frequencies;Gastroenterology;Gender;Genetic;Genomics;Goals;hazard;Health care facility;Health Policy;health practice;Healthcare Systems;Hepatitis B Infection;Hepatitis B Virus;Hepatology;Histologic;improved;India;Institution;interest;Invaded;Investigation;Ionizing radiation;K-Series Research Career Programs;Lesion;low and middle-income countries;Malignant neoplasm of liver;Malignant Neoplasms;Mentors;Mentorship;Methods;minimally invasive;Mitochondria;Mitochondrial DNA;Modality;Molecular;Molecular Biology;MRI Scans;Neoplasm Metastasis;Nigeria;Nigerian;Nodule;Normal Range;novel;Outcomes Research;Oxidative Stress;Participant;participant enrollment;Patient Care;Patients;Performance;peripheral blood;Peripheral Blood Mononuclear Cell;Persons;Ploidies;Policies;Population;Primary carcinoma of the liver cells;Primary Malignant Neoplasm of Liver;programs;Public Health;Radiation exposure;Research;Research Activity;Research Methodology;Research Personnel;Research Project Summaries;Resource-limited setting;Resources;Risk;Risk Factors;Safety;Scanning;Scourge;screening;Screening procedure;Sensitivity and Specificity;Sequence Analysis;Serum;Severities;sex;skill acquisition;skills;Smoking;Specificity;Statistical Data Interpretation;Techniques;Testing;therapeutic target;Time;Tissue Sample;Tissues;Training;Training Activity;Translating;Translational Research;translational scientist;treatment center;Tumor Markers;ultrasound;United States National Institutes of Health;Vaccination;Work;Writing;X-Ray Computed Tomography;α-Fetoproteins

PROJECT_TITLE: Use of Peripheral Blood Mononuclear Cells Mitochondrial DNA Content to Detect Hepatocellular Carcinoma in Hepatitis B Virus Infected Nigerians.

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Brain Disorders;Cerebrovascular;Infectious Diseases;Lung;Neurosciences;Pneumonia;Pneumonia and Influenza;Rehabilitation;Stroke

ORG_DEPT: NEUROLOGY

PHR: Project Narrative Post-stroke pneumonia is one of the most common complications after stroke and leads to poor outcomes after stroke. The overall goal of the proposal is to identify mechanisms that lead to severe pneumonia after stroke and that lead to poor neurological outcomes with the goal of identifying new treatment targets.

PI_NAMEs: DELA CRUZ, CHARLES S;SANSING, LAUREN H (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Affect;Aging;Alveolar;Anti-Bacterial Agents;Antibiotics;antimicrobial;Apoptosis;Aspiration Pneumonia;Bacterial Infections;behavioral outcome;Blood capillaries;Body Weight;Brain;brain endothelial cell;Brain Injuries;Bronchoalveolar Lavage Fluid;Cause of Death;Cells;Cerebral Ischemia;chemokine;Clinical Trials;Cognitive;Complication;cost;Critical Care;CXCL1 gene;cytokine;Data;disability;Endothelial Cells;Event;Experimental Models;experimental study;extracellular;Feasibility Studies;Female;Flow Cytometry;Foundations;Functional impairment;Gene Expression Profiling;Genetic Transcription;Goals;Growth;Host Defense;Immune response;Immunity;Immunofluorescence Immunologic;Immunologist;immunoregulation;Immunosuppression;Impairment;improved;improved outcome;In Vitro;in vivo;Incidence;Infection;Inflammatory;Inflammatory Response;Interferon Receptor;Interferon Type I;Interferons;Interleukin-6;Investigation;Ischemic Stroke;Klebsiella Infections;Klebsiella pneumoniae;Knock-out;Lung;Lung infections;male;Microglia;Middle Cerebral Artery Occlusion;migration;Modeling;monocyte;Morbidity - disease rate;mortality;Mus;Natural Immunity;neurobehavioral;Neuroimmune;Neuroimmunomodulation;neuroinflammation;Neurological outcome;neurological recovery;Neurologist;neutrophil;Neutrophil Activation;Neutrophil Infiltration;Organ;Outcome;Pathogenicity;Patients;Peripheral;Physicians;Pneumonia;post stroke;Predisposition;prevent;Production;Prognosis;prophylactic;Recovery;Recovery of Function;Regimen;Reperfusion Therapy;Research Personnel;Resolution;Respiratory Tract Infections;response;Risk;Role;Signal Transduction;single-cell RNA sequencing;Spleen;Stains;Stroke;stroke outcome;stroke patient;stroke recovery;Structure of parenchyma of lung;Supportive care;T-Lymphocyte;targeted treatment;Testing;therapeutic target;Time;United States;Up-Regulation;Weight Gain;Work

PROJECT_TITLE: Reciprocal brain-lung responses in post-stroke pneumonia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CN-E(90)S]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Patient Safety;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: LOS ANGELES

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Relevance to Public Health Evidence-based preventive health services are vastly underutilized by older Americans. This proposal’s promising multilevel intervention will stimulate greater use of the Medicare Annual Wellness Visit, an established but underused mechanism that gives providers dedicated time to focus on preventive health services. The anticipated increase in preventive health services stemming from greater Annual Wellness Visit use will improve population health and lower mortality, particularly in at-risk racial/ethnic minority patients.

PI_NAMEs: TARN, DERJUNG M (contact)

PROGRAM_OFFICER_NAME: KIM, THERESA YOUNGJOO

PROJECT_TERMS: Academy;Address;Adult;Advisory Committees;Agreement;American;Breast Cancer Detection;Caring;Cessation of life;Clinical Decision Support Systems;cloud based;colorectal cancer screening;colorectal cancer treatment;Communities;Country;Coupled;Data;Data Coordinating Center;data sharing;Dedications;design;Early Diagnosis;Early treatment;Effectiveness;Electronic Health Record;electronic health record system;Electronics;Eligibility Determination;ethnic disparity;ethnic diversity;ethnic minority;evidence base;Family Physicians;Geography;Goals;health data;health service use;Health Services Needs;Herpes zoster disease;human old age (65+);Immunization;improved;Individual;individual patient;Infection prevention;Influenza;Intervention;intervention cost;intervention effect;intervention refinement;Low income;Malignant Breast Neoplasm;Medicare;meetings;minority patient;Morbidity - disease rate;mortality;National Cancer Institute;Notification;novel;Nursing Staff;older adult;older patient;Online Systems;Outcome Assessment;patient registry;Patients;Phase;Physicians;pilot test;Pneumonia;population health;Population-Based Registry;practice-based research network;pragmatic trial;Preventive care;Preventive Health Services;Preventive service;primary care practice;Prostate;Provider;Public Health;racial disparity;racial diversity;racial minority;Randomized, Controlled Trials;Recommendation;Research;Risk;Screening for cancer;Services;Solo Practices;stem;Syndrome;therapy design;Time;tool;Training;United States;United States Preventative Services Task Force;uptake;Vaccination;Videoconferencing;Visit;wellness visit;Work;Writing

PROJECT_TITLE: Medicare Annual Wellness Visit Practice Redesign Toolkit: A Tailored Intervention to Improve Preventive Health Service Use


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Hematology;Infectious Diseases;Microbiome;Pediatric;Prevention;Sepsis;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: PROJECT NARRATIVE Bloodstream infections (BSI) caused by bacteria translocating across an injured mucosa are a significant cause of morbidity and mortality in patients who undergo stem cell transplantation. There are no known strategies to prevent BSI from translocation of BSI through the injured mucosa, including those through the oral cavity. Through this study, we will determine the effectiveness of twice daily xylitol-wipe application on reducing BSI from oral organisms through a randomized, multicenter, double-blind, placebo-controlled study in pediatric stem cell transplant recipients.

PI_NAMEs: DANDOY, CHRISTOPHER EUGENE (contact)

PROGRAM_OFFICER_NAME: FISCHER, DENA

PROJECT_TERMS: Adherence;Admission activity;Adopted;arm;Bacteremia;Bacteria;Bacterial Translocation;Blood Circulation;Bone Marrow Transplantation;Childhood;Clinical;Clinical Trials;clinically relevant;Communicable Diseases;cost estimate;Data;Dental;Dental Plaque;Dentists;Diagnosis;Double-Blind Method;effectiveness evaluation;expectation;Fiber;fruits and vegetables;Funding Opportunities;Gingiva;Gingivitis;Goals;graft vs host disease;Healthcare;Immune System Diseases;improved outcome;Incidence;Infection;Inflammation;injured;Injury;innovation;Intensive Care Units;Intervention;microbial;microbiome analysis;Morbidity - disease rate;mortality;Mucositis;Mucous Membrane;Multi-Institutional Clinical Trial;National Institute of Dental and Craniofacial Research;Oral;oral bacteria;oral care;Oral cavity;oral infection;oral microbiome;Oral mucous membrane structure;oral plaque;Oral Ulcer;Organism;Pathogenicity;Patients;Physicians;placebo controlled study;Population;Positioning Attribute;preservation;prevent;Prevention;Prevention strategy;Randomized;Randomized, Controlled Trials;Research;response;Route;Saliva;Secondary to;Sepsis;Septic Shock;Specialist;standard of care;Stem cell transplant;Streptococcus mitis;Sugar Alcohols;Testing;Time;Transplant Recipients;trial planning;U-Series Cooperative Agreements;United States;Work;Xylitol

PROJECT_TITLE: Reduction of bloodstream infections from oral organisms in pediatric stem cell transplant: a randomized multicenter double-blind placebo-controlled study evaluating twice daily oral xylitol


ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE We propose to develop and validate an functional magnetic resonance imaging (fMRI) technique for mapping awake mouse brain function. Successful completion of this work will create a new fMRI data acquisition and on- line reconstruction package on the preclinical MRI platform, for which mouse models are frequently used to study brain function/dysfunction. Our experiments will also examine the contrast mechanisms of this non-invasive fMRI technique, explore a novel means to further boost contrast, and overcome the key limitations of the conventional fMRI that could translate to significant public health impact.

PI_NAMEs: SHIH, YEN-YU IAN (contact)

PROGRAM_OFFICER_NAME: BARRY, ROBERT LEO II

PROJECT_TERMS: 3-Dimensional;Accounting;Acoustics;Address;Affect;Agreement;Anesthesia procedures;Animals;awake;Behavioral;Benchmarking;Blood;blood oxygen level dependent;blood oxygenation level dependent imaging;Brain;Brain imaging;Brain Mapping;brain tissue;brain volume;Calcium;cerebral blood volume;Cerebrovascular Circulation;Communities;contrast enhanced;Data;data acquisition;Data Analyses;Detection;Development;Echo-Planar Imaging;Electromagnetics;Equation;experience;experimental study;Fiber;Functional disorder;Functional Magnetic Resonance Imaging;Future;Gases;Goals;graphical user interface;Head;hemodynamics;Image;Imaging Techniques;Imaging technology;improved;in vivo;innovation;instrument;Knowledge;magnetic field;Magnetic Resonance Imaging;Manganese;Maps;Marketing;Measurement;Methods;Modality;Modeling;Molecular;Morphologic artifacts;Motion;mouse model;Mus;Music;neuroimaging;Neurons;Noise;novel;novel strategies;Outcome;Oxygen;Performance;Phase;Photometry;pre-clinical;Predisposition;Protocols documentation;Public Health;radio frequency;Ramp;reconstruction;Research;Resolution;response;Rest;Rodent;sample fixation;Sampling;Scheme;Sensitivity and Specificity;Signal Transduction;spatiotemporal;Specificity;Stress;Surrogate Markers;Techniques;Technology;Time;tissue oxygenation;Tissues;tool;Translating;uptake;Vendor;Venous;Work

PROJECT_TITLE: SORDINO-fMRI for mouse brain applications

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Genetics;Hematology;Rare Diseases

ORG_CITY: CHICAGO

ORG_DEPT: PATHOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Successful completion of this proposed study will help elucidate how age-related inflammatory bone marrow microenvironment influences the development and progression of myelodysplastic syndromes (MDS). Understanding these processes may lead to the identification of novel targets for the treatment of MDS.

PI_NAMEs: JI, PENG  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Age;age related;Aging;aging related;Biological Assay;Bone Development;Bone Marrow;Bone Marrow Cells;Bone remodeling;CASP1 gene;CD34 gene;Cells;Cues;cytokine;Data;Development;Disease;Disease Progression;Dysmyelopoietic Syndromes;experimental study;Family;Fc Receptor;gain of function;Genes;Genetic;Hematopoietic;Hematopoietic stem cells;high risk;IL-6 inhibitor;Immune signaling;Immunotherapy;In Vitro;in vivo;Individual;Inflammasome;Inflammation;Inflammatory;inhibitor;Innate Immune System;Interleukin 6 Receptor;Interleukin-1;Interleukin-6;Knock-out;Knockout Mice;leukemia;Mediating;Medical;Modeling;mouse model;Mus;mutational status;NF-kappa B;novel;Pathogenesis;Pathway interactions;Patients;Permeability;Phenocopy;Phenotype;Population;prevent;Process;Proliferating;Proto-Oncogene Protein c-kit;Reporter;Role;single-cell RNA sequencing;Source;Stromal Cells;System;Testing;Therapeutic;Transgenic Mice;transplant model;Transplantation;Up-Regulation;Wild Type Mouse;Xenograft procedure

PROJECT_TITLE: Targeting gasdermin D to treat myelodysplastic syndromes

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Brain Disorders;Genetics;Human Genome;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: NARRATIVE This grant will develop and apply a novel genomic technology to study rare astrocyte subsets important to multiple sclerosis.

PI_NAMEs: ABATE, ADAM R. (contact);CHAN, JONAH R;CONDELLO, CARLO L

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Address;Alternative Splicing;Astrocytes;Atlases;Biological Markers;Biology;brain cell;Cell Separation;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;conditional knockout;CRISPR/Cas technology;Cytometry;detection method;Disease;disorder control;DNA;DNA Markers;epigenomics;Experimental Autoimmune Encephalomyelitis;Gene Expression Profile;Genetic;genetic corepressor;Genomics;Grant;Human;in vivo;interest;Investigation;knock-down;Knockout Mice;Link;Methods;mouse model;Multiple Sclerosis;Mus;Mutation;NCOR2 gene;Nerve Degeneration;Nervous System Disorder;novel;NR3C2 gene;Nuclear Receptors;Nucleic Acids;Pathogenesis;Pathogenicity;Pathology;Physiological;Population;posttranscriptional;pre-clinical;Pre-Clinical Model;Prions;Receptor Signaling;Reporting;response;RNA;RNA marker;RNA Splicing;Role;Sampling;Signal Transduction;single cell genomics;single cell technology;single molecule;single-cell RNA sequencing;Surface;Technology;Therapeutically Targetable;Transcript;transcription factor;Transcriptional Activation;transcriptome sequencing;transcriptomics;Virus Integration;XBP1 gene

PROJECT_TITLE: Identification of regulatory mechanisms operating in rare pathogenic astrocyte subsets in multiple sclerosis with a novel genomic technology

STUDY_SECTION: GCAT

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE  Coronaviruses, including the pandemic SARS-CoV-2, have posed severe threats to global health and led to substantial economic loss. However, the limited knowledge of coronavirus biology and pathogenesis greatly hinders the development of effective antiviral treatments. This work aims to understand how the dynamic interplay between SARS-CoV-2 and host factors controls viral gene expression with the goal of revealing novel druggable targets for innovative strategies against these highly pathogenic coronaviruses.

PI_NAMEs: LIU, CHANG  (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;3' Untranslated Regions;5' Untranslated Regions;Active Sites;Address;Affect;Affinity Chromatography;Anti-viral Agents;Anti-viral Response;arms race;Binding;biochemical tools;Biological;Biological Models;Biological Process;Biology;Biophysics;Cells;Color;Communicable Diseases;Complex;Coronavirus;coronavirus therapeutics;COVID-19 pandemic;COVID-19 therapeutics;Cryo-electron tomography;Cryoelectron Microscopy;Deposition;design;Development;DNA-Directed RNA Polymerase;Drug resistance;Economics;experimental study;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;global health;Goals;GPRC5C gene;Host Defense Mechanism;human coronavirus;In Situ;innovation;Integration Host Factors;Interferons;Intervention;Kinetics;Knowledge;Life Cycle Stages;Link;Mass Spectrum Analysis;Mediating;Methyltransferase;Modification;Molecular;mutant;new therapeutic target;novel;novel coronavirus;novel strategies;novel therapeutics;Outcome;pandemic disease;Pathogenesis;Pathogenicity;Process;programs;Proteins;reconstitution;reconstruction;Regulation;Replication-Associated Process;Replicon;Reporter;Research;research and development;RNA Biochemistry;RNA chemical synthesis;RNA Polymerase Inhibitor;RNA Viruses;RNA-Directed RNA Polymerase;Role;SARS-CoV-2 genome;sensor;Signal Pathway;single molecule;single-molecule FRET;Stream;structural biology;success;Surface;System;targeted agent;Therapeutic;therapeutic development;therapeutically effective;Time;tool;Transcription Initiation;Transcription Process;Translations;Tretinoin;Vaccines;Viral;Viral Genes;Viral Pathogenesis;viral RNA;virology;Virus;Virus Diseases;virus host interaction;Virus Replication;Visualization;Work

PROJECT_TITLE: Emerging mechanisms of viral gene regulation from battles between host and SARS-CoV-2


ORG_CITY: AUGUSTA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Vascular diseases involve a phenotypic switch of vascular smooth muscle cells (VSMCs) to diverse, pathological cell states. I will study a transcription factor, MEIS1, that safeguards the VSMC differentiated phenotype thus preserving normal vascular homeostasis. The current proposal utilizes innovative and genetically edited mouse models, vascular smooth muscle cultures, and collaborations with pioneers in the field, to gain foundational insight into the functional role and transcriptional regulation of MEIS1 in vivo.

PI_NAMEs: SALEM, AMR  (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Alleles;Angioplasty;Antibodies;Arteries;atherogenesis;Atherosclerosis;Award;Binding;Binding Sites;biobank;Biological Assay;Blood Vessels;career;Cell Cycle;cell dedifferentiation;Cell Differentiation process;cell motility;cell type;Cells;ChIP-seq;Chromatin;chromatin immunoprecipitation;Chromosomes;cofactor;Collaborations;combat;Coronary;Coronary artery;Cre driver;Data;data mining;Detection;Disease;Down-Regulation;Elements;Endarterectomy;Enhancers;epigenetic marker;epigenome;Epitopes;Event;EVI1 gene;Foundations;gain of function;Gel;Gene Expression;Genes;Genetic Transcription;genome editing;genome-wide analysis;Homeostasis;Human;in vivo;Inflammation;inhibitor;Injury;innovation;insight;Knockout Mice;loss of function;LoxP-flanked allele;Luciferases;Maintenance;MEIS1 gene;Mentors;Methods;migration;Mission;mouse model;multiple omics;Mus;Mutate;Myelogenous;myocardin;National Heart, Lung, and Blood Institute;novel;Nuclear;Nuclear Accidents;Paper;Pathologic;Pathology;Patients;Phase;Phenotype;Positioning Attribute;preservation;prevent;prime editing;Proliferating;promoter;Promoter Regions;protein expression;Proteins;Pulmonary Hypertension;Rattus;Regulation;Regulatory Element;Reporting;Research;Research Personnel;Resources;Response Elements;restenosis;Rodent;Role;Serum Response Factor;Signal Pathway;Smooth Muscle Myocytes;spatiotemporal;Stenosis;Testing;therapeutic target;Training;Transactivation;Transcription Coactivator;transcription factor;Transcriptional Regulation;transcriptome;transcriptome sequencing;transcriptomic profiling;transcriptomics;Validation;Vascular Diseases;vascular injury;Vascular Smooth Muscle;vascular smooth muscle cell migration;vascular smooth muscle cell proliferation;virtual;Work

PROJECT_TITLE: Function and Regulation of MEIS1 in Vascular Disease

STUDY_SECTION: MTI

STUDY_SECTION_NAME: NHLBI Mentored Transition to Independence Study Section[MTI(MA)]


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

ORG_CITY: SANTA CRUZ

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: The proposed research will provide deep insight into the cellular and molecular mechanisms by which cortical neural stem cells generate different types of neurons and macroglia during development. Thus results from the proposed studies will have fundamental importance in stem cell biology, brain development, and human disease prevention and treatment.

PI_NAMEs: CHEN, BIN  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Applications Grants;Astrocytes;ATAC-seq;Binding;Birth;Brain;Brain region;Cell Lineage;cell motility;Cell Physiology;cell type;Cells;Central Nervous System;Cerebral cortex;ChIP-seq;Cleavage Under Targets and Release Using Nuclease;Defect;Development;disorder prevention;Drosophila genus;Enhancers;Etiology;excitatory neuron;Gene Expression;Generations;Genes;Genetic Transcription;Germ Cells;gliogenesis;Glutamates;Goals;human disease;Individual;insight;Interneurons;Investigation;Knowledge;macroglia;migration;Molecular;mouse genetics;Multipotent Stem Cells;Mus;nerve stem cell;neural circuit;neuroblast;Neurodevelopmental Disorder;neurogenesis;Neuroglia;Neurons;Neurosciences;olfactory bulb;oligodendrocyte lineage;Oligodendroglia;Outcome;Pathway interactions;Pattern;Population;Process;Production;progenitor;promoter;Publications;Radial;Reporting;Research;segregation;Signal Transduction;single-cell RNA sequencing;Specific qualifier value;stem cell biology;Technology;Testing;transcription factor;Transcription Repressor;transcriptome sequencing;Ventricular

PROJECT_TITLE: Lineage Progression of Cortical Neural Stem Cells


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Lung;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Acute respiratory distress syndrome (ARDS)—which manifests as acute lung injury—is characterized by an exaggerated host immune response and cellular damage, as a result of which it is a major cause of disability and death. There is an urgent need to better understand host immune response mechanisms in the lung, with the goal of yielding new strategies to improve ARDS treatment. Our proposal directly addresses this need by investigating and employing C3—an evolutionary conserved complement protein central to host defense—to reduce the morbidity and mortality associated with ARDS due to its ability to protect the lung.

PI_NAMEs: KULKARNI, HRISHIKESH SATISH (contact)

PROGRAM_OFFICER_NAME: SHENOY, SIDDHARTH KAUP

PROJECT_TERMS: Acute Lung Injury;Acute Respiratory Distress Syndrome;Address;Affect;airway epithelium;Alveolar;alveolar epithelium;Alveolar Macrophages;Area;Binding;Bioinformatics;Biological Assay;Biology;Cell Compartmentation;Cell Death;Cell Death Induction;cell injury;Cell Physiology;Cell Survival;cell type;Cells;Cessation of life;Characteristics;Circulation;Clustered Regularly Interspaced Short Palindromic Repeats;Compensation;Complement;Complement 3a;Complement 3b;complement C3 precursor;Complement Factor B;complement system;conditional knockout;CRISPR screen;cytokine;Cytoprotection;Data;Dependence;design;disability;Epithelial Cells;Epithelium;Experimental Models;extracellular;Extracellular Space;Gene Delivery;Genetic;Goals;Host Defense;Host Defense Mechanism;Human;human model;Immune;immune cell infiltrate;Immune response;improved;In Vitro;in vivo;in vivo Model;Inflammatory;Injury;Knock-out;Knockout Mice;Knowledge;Libraries;Liver;Lung;lung injury;Macrophage;Mediating;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Myeloid Cells;National Heart, Lung, and Blood Institute;novel therapeutics;overexpression;pathogen;Phagocytosis;Population;Predisposition;Principal Investigator;Process;Production;protective effect;Proteins;Pseudomonas aeruginosa;Pseudomonas aeruginosa pneumonia;Publishing;receptor;Research Personnel;Research Priority;resilience;response;response to injury;Role;Site;Source;Stress;Testing;Thinking;Time;Tissues;Transgenic Mice;uptake;Wild Type Mouse;Work

PROJECT_TITLE: Lung epithelial cell-derived C3 in acute lung injury

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Mental Health;Neurosciences;Pediatric;Social Determinants of Health

ORG_CITY: ATLANTA

ORG_DEPT: PEDIATRICS

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE Prior social experiences influence our everyday choices; for instance, we might favor a particular restaurant because it’s where we had a first date with our spouse. This process likely reinforces the value of social information but is not well understood neurobiologically. We will study the developmental processes by which organisms come to prioritize social information and use it to make choices.

PI_NAMEs: GOURLEY, SHANNON LEIGH (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Adolescence;Adolescent;Affinity;Alzheimer's disease risk;Amygdaloid structure;anterograde transport;base;Behavior;Behavioral;Binding;Biological Assay;Biological Availability;Brain;Brain-Derived Neurotrophic Factor;career;cell type;Cells;cofactor;Cognitive;cognitive function;Complex;critical period;Decision Making;Dendritic Spines;Development;Developmental Process;Dissociation;early life adversity;Eating;Empathy;excitatory neuron;experience;experimental study;Food;Future;Goals;Grant;Human;Incentives;information processing;insight;Investigation;Learning;Length;Life;Mammals;Medial;Mediating;Mental Health;Modality;model organism;Mus;National Institute of Mental Health;National Institute of Neurological Disorders and Stroke;Nature;neural circuit;Neurobiology;Neurons;neurotrophic factor;novel;novel therapeutics;Nucleus Accumbens;Operant Conditioning;Organism;Outcome;overexpression;Phosphotransferases;Population;postsynaptic;Prefrontal Cortex;premature;Process;Protein Isoforms;Proteins;PTK2B gene;receptor;Restaurants;Rewards;Risk Factors;Rodent;Role;Signal Transduction;Site;social;Social Behavior;Social Controls;Social Functioning;social influence;Social Interaction;Social isolation;Social Values;Socialization;Spouses;Strategic Planning;Stress;Testing;Therapeutic;Training;Tropomyosin;United States National Institutes of Health;Up-Regulation;Viral;willingness;young adult

PROJECT_TITLE: Understanding how social interactions influence reward-seeking behaviors: Developmental mechanisms

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: Project Narrative Adenosine methylation (m6A) is a highly prevalent RNA modification that has been linked to several human cancers. The m6A methyltransferase complex has emerged as a potential therapeutic target; however, efforts to identify methyltransferase inhibitors have been hampered by the lack of methods that provide a cellular readout of adenosine methylation on a high-throughput scale. Here, we will develop a novel genetically encoded m6A sensor system that provides a fluorescence-based readout for mRNA methylation which can be used both for high-throughput drug discovery efforts as well as studies investigating m6A biology and its contribution to cancer.

PI_NAMEs: MEYER, KATHRYN D (contact)

PROGRAM_OFFICER_NAME: DUECK, HANNAH RUTH

PROJECT_TERMS: Address;Adenosine;Antibodies;Benchmarking;Biological Assay;Biology;Cancer Biology;Cell Differentiation process;Cell Line;Cell Physiology;cell type;Cells;Chemicals;Complex;Consumption;cost;cost effective;Couples;cross reactivity;Data;Deposition;design;detection method;Development;drug candidate;drug discovery;Drug Targeting;Fluorescence;Gametogenesis;Gene Expression;genetic manipulation;genome wide methylation;Goals;high throughput screening;Human;human disease;immunoregulation;improved;in silico;In Vitro;in vivo;inhibitor;Investigation;Learning;Life Cycle Stages;Link;Malignant Neoplasms;Mass Spectrum Analysis;Measurement;Measures;Memory;Messenger RNA;Methods;Methylation;Methyltransferase;Modification;Molecular;neurodevelopment;Neurons;novel;novel therapeutics;Oncogenes;Performance;Pharmaceutical Preparations;Physiological Processes;Play;Predisposition;Protein Methyltransferases;Proteins;Reader;Regulation;RNA;RNA methylation;Role;screening;sensor;small molecule;stem cell proliferation;Structure;System;Technology;therapeutic target;Time;tool;tumor progression;Tumor Suppressor Proteins;Virus

PROJECT_TITLE: A High-Throughput Screening Platform to Discover RNA Methylation Inhibitors


ORG_CITY: MINNEAPOLIS

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE Magnetic resonance spectroscopy (MRS) can provide metabolic concentration noninvasively in the human brain. The tools for measuring metabolism are very limited. This research project will develop and evaluate the tools, which would allow the robust measurement of both metabolic concentrations and metabolic rates in the human brain.

PI_NAMEs: BOGNER, WOLFGANG ;MARJANSKA, MALGORZATA  (contact)

PROJECT_TERMS: Acetates;Back;Brain;Brain Diseases;brain metabolism;Brain region;Calibration;Chemicals;Citric Acid Cycle;Data;Dementia;Deuterium;Development;Fostering;Future;gamma-Aminobutyric Acid;Glucose;Glutamates;Glutamine;Glycolysis;Goals;healthy volunteer;Human;Human body;human data;Image;imaging approach;Imaging Device;imaging modality;improved;in vivo;Label;magnetic field;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Malignant Neoplasms;Measurement;Measures;Mental disorders;Metabolic;metabolic imaging;Metabolic Pathway;metabolic rate;Metabolism;metabolome;Methods;Monitor;Neurosciences;novel;Nutrient;Pathogenesis;Pathologic;Pathology;Performance;Pharmaceutical Preparations;Physiological;Positron-Emission Tomography;Protons;Rattus;Reproducibility;Research;Research Project Grants;Scanning;Sensitivity and Specificity;sensor;Specificity;spectroscopic imaging;Spectrum Analysis;success;Techniques;Technology;Tissues;tool;Translating;Translations;Work

PROJECT_TITLE: Novel 10.5 T deuterium-based MRS/I method to measure brain metabolism

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Chronic Pain;Neurosciences;Pain Research;Wound Healing and Care

ORG_CITY: PITTSBURGH

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative While surgical incision healing is of tantamount importance in restoring the integrity of skin and protecting against invading pathogens, the essential role of cutaneous sensory afferents in recruiting and activating immune cells to the surgical site is not fully understood. The goal of the proposed research is to advance the understanding of neural-immune signaling during surgical wound repair and of the impact of peripheral nerve blocks (PNBs), an indispensable perioperative tool, on this interaction. This work will advance our understanding of how sensory neurons and PNBs impact wound repair and lead to improved, personalized perioperative care of patients.

PI_NAMEs: RITTER JONES, MARSHA ELIZABETH (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Acute;Affect;Afferent Neurons;Antiinflammatory Effect;Architecture;Calcitonin Gene-Related Peptide;Cells;chronic wound;Communication;Conduction Anesthesia;Cutaneous;Data;Genes;Goals;GTP-Binding Proteins;healing;Immune;Immune response;Immune signaling;Immune system;Impaired healing;improved;Inflammation;Inflammatory;Inflammatory Response;Innate Immune System;Invaded;Knockout Mice;Local Anesthetics;Medicare;Modeling;Mus;Myelogenous;Nerve Block;neural;Neuroimmune;neuron loss;Neurons;Neuropeptides;novel;Operative Surgical Procedures;Pain;pain behavior;pathogen;Patient Care;peptide P;Perioperative;Perioperative Care;Peripheral Nerves;Phase;programs;Publishing;receptor;recruit;Research;response to injury;Role;sciatic nerve;Sensory;Signal Transduction;Site;Skin;Substance P;Surgical incisions;Surgical wound;Tissues;tool;transcriptomics;Work;wound care;wound healing

PROJECT_TITLE: Neuroimmune signaling in surgical wound healing and modulation by regional anesthesia

STUDY_SECTION: MRAD

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


ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Sepsis-induced acute kidney injury is associated with high mortality. This deadly disease lacks effective therapeutics due in large part to poorly understood pathophysiological mechanisms. The proposed research is highly relevant to the NIH's mission as well as to public health because the discovery of pathophysiological mechanisms involved in sepsis-induced kidney injury will lead to the development of rational therapeutic and preventative interventions at the bedside.

PI_NAMEs: HATO, TAKASHI  (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Acceleration;Acute Renal Failure with Renal Papillary Necrosis;Adenosine;Animal Model;Anti-Inflammatory Agents;Anti-viral Response;Antibodies;Antisense Oligonucleotides;Bacteremia;Bacterial Infections;Binding;Complex;Coupled;Cytoplasm;Data;Development;Disease;Double Effect;Double-Stranded RNA;Elements;Endotoxins;Eukaryotic Initiation Factors;Functional disorder;Genes;Genetic Transcription;Heart;Hour;Immunoprecipitation;Infection;Inflammation;Inflammatory;Injury to Kidney;Inosine;Intensive Care Units;Interferons;Kidney;Kidney Failure;Link;Mediating;Mediator;mimicry;Mission;Mitochondria;Modeling;mortality;Multiple Organ Failure;Mus;Nature;novel diagnostics;novel therapeutics;Nuclear;Nucleic Acids;Open Reading Frames;Organ;Organ failure;pathogen;Pathologic;Pathway interactions;Phase;Phosphorylation;Phosphotransferases;preventive intervention;Prognosis;programs;Prokaryotic Initiation Factor-2;Protein Dephosphorylation;Proteins;Public Health;Publishing;receptor;Recovery;Reporting;Repression;Research;RNA;RNA Binding;RNA Editing;Role;Sepsis;septic;Severities;Site;Source;Sterility;Stimulus;Stress;stress granule;successful intervention;Supportive care;Syndrome;targeted treatment;Therapeutic Intervention;therapeutically effective;timeline;tissue injury;TLR3 gene;TLR4 gene;transcriptome sequencing;Translational Repression;Translations;translatome;United States National Institutes of Health;Untranslated Regions;Up-Regulation;Viral;Viral Genes;viral RNA;Virus Diseases;Work

PROJECT_TITLE: The role of antiviral programs in bacterial sepsis

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Genetics

ORG_CITY: BOSTON

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: Project Narrative Cells in many organisms contain important proteins called nucleosome chaperones that regulate how gene instructions in DNA are copied into RNA before being used to make other proteins. We propose to study this process with tools that let us measure the behavior of single molecules at a time, focusing on how the function of nucleosome chaperones change depending on decorations on DNA-packaging proteins that change with the energy status of the cell. Because cancer cells have more nucleosome chaperone proteins and different decorations on their DNA-packing proteins, and chaperone proteins are involved in replication of viruses, our results may be used in the development of cancer therapies, as well as antiviral therapeutics.

PI_NAMEs: WILLIAMS, MARK C (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Acylation;Affect;Anti-viral Agents;Atomic Force Microscopy;Behavior;Binding;Biological Process;cancer cell;cancer therapy;Cells;Charge;Chromatin;chromatin modification;chromatin remodeling;Complex;Crystallins;Data;Development;Disease;Dissociation;DNA;DNA Integration;DNA Packaging;DNA-Directed RNA Polymerase;Equilibrium;Excision;Fluorescence;Genes;Genetic Transcription;Growth Factor;hepatoma-derived growth factor;histone methylation;histone modification;Histones;HIV-1;Individual;Instruction;Integrase;Kinetics;laser tweezer;Learning;lens epithelium-derived growth factor;Lysine;Measures;Mediating;Metabolic;Methods;mimetics;Modification;Molecular;Molecular Chaperones;monomer;mutant;Nucleosomes;optic tweezer;Organism;Physiological;Play;preservation;Process;Proteins;Reader;RNA;Role;single molecule;Site;Specificity;Stress;Testing;Time;tool;Virus Replication

PROJECT_TITLE: Chromatin modifications that enhance DNA accessibility

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: DALLAS

ORG_DEPT: SURGERY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE  A leading cause of microbial infections in hospitalized patients is Gram-negative bacteria, which release the cell wall component lipopolysaccharide capable of activating innate immune pathways. We postulate that ACOD1 is a mediator of lethal bacterial infection independent of its canonical function in itaconate production. Our research could not only provide new therapeutic targets for infectious diseases, but also establish promising uses for anticancer drugs in limiting inflammatory responses.

PI_NAMEs: TANG, DAOLIN  (contact)

PROGRAM_OFFICER_NAME: NELSON, SHAKIRA M

PROJECT_TERMS: Aconitic Acid;Adaptor Signaling Protein;Animals;Anti-Inflammatory Agents;Antineoplastic Agents;Attenuated;Automobile Driving;Bacterial Infections;Binding;Biochemistry;Biological Response Modifiers;Carbon;Carboxy-Lyases;CDK2 gene;Cell Wall;Cells;Clinical;cohort;Communicable Diseases;Complex;cytokine;cytokine release syndrome;Development;Dinucleoside Phosphates;Drug Screening;efficacy evaluation;Enzymes;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Erlotinib;fighting;gain of function mutation;Genes;Genetic;Genetic Transcription;Gram-Negative Bacteria;Guanosine Triphosphate Phosphohydrolases;Hospitalization;Immune system;Immune System Diseases;Immunity;improved;Infection;infectious disease treatment;Inflammation;Inflammatory;Inflammatory Response;inhibitor;innate immune pathways;Innate Immune Response;insight;jun Oncogene;Lipopolysaccharides;Macrophage;Mediating;Mediator;Metabolism;microbial;Mitochondria;monocyte;Multiple Organ Failure;Mus;Myeloid Cells;Natural Immunity;new therapeutic target;next generation sequencing;Non-Small-Cell Lung Carcinoma;novel;novel therapeutic intervention;Pathway interactions;Patients;Periodicity;pharmacologic;Phosphorylation;Positioning Attribute;pre-clinical;prevent;Production;protein complex;Proteins;Research;response;Role;Safety;Severities;Signal Pathway;Signal Transduction;Stimulus;Testing;therapeutic target;TNF gene;transcription factor;Transgenic Animals;Up-Regulation

PROJECT_TITLE: Targeting ACOD1 to attenuate innate immune responses to lethal infections

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


NIH_SPENDING_CATS: Microbiome

ORG_CITY: HANOVER

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: PROJECT NARRATIVE The bacterial residents of the gut impact human health. The specific makeup of these bacterial communities can differ dramatically between people, yet how these differences arise is not understood. My research combines computational analyses with experimentation to generate unique insights into the forces that sculpt the inhabitants of the human gut, through the lens of interbacterial antagonism and defense.

PI_NAMEs: ROSS, BENJAMIN  (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TITLE: Mechanisms of adaptation to interbacterial antagonism by the human gut microbiota

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


NIH_SPENDING_CATS: Bioengineering;Genetics;HIV/AIDS;Infectious Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: PHILADELPHIA

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: PROJECT NARRATIVE: PUBLIC HEALTH RELEVANCE There are ~40 million people world-wide infected by the Human Immunodeficiency Virus Type 1 (HIV-1, commonly referred to as HIV); there is currently no cure, and antiretroviral treatment is the primary treatment option. As antiretroviral treatment eventually fails over time due to the development of drug resistance, we will develop new computational tools for forecasting HIV evolutionary trajectories under therapeutic selection pressure leading to drug resistance, using high resolution all atom molecular dynamics simulations together with physics-based machine learning models of sequence co-variation. The computational work, complimented by structural, biophysical, and virological studies, will lead to the development of surveillance tools to forecast the response of viral systems to the selection pressure of antiviral therapeutics which may be used to individualize and develop new combination antiretroviral therapies.

PI_NAMEs: LEVY, RONALD  (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Active Sites;Affect;Affinity;Amino Acids;Anti-viral Agents;antiretroviral therapy;Base Sequence;Benchmarking;Binding;biophysical properties;Biophysics;Calibration;Capsid;Capsid Proteins;Chemicals;Clinical;clinically relevant;computer studies;computerized tools;Cryoelectron Microscopy;Data;Defect;Development;drug discovery;Drug resistance;drug resistance development;Drug resistance pathway;Environment;experience;experimental study;fitness;Free Energy;Genetic Epistasis;Goals;HIV;HIV Genome;HIV Integrase;HIV Integrase Inhibitors;HIV-1;improved;inhibitor;Integrase;interfacial;Knowledge;Laboratories;Lead;Ligand Binding;Liquid substance;Machine Learning;machine learning model;Maps;Measurement;Methods;Modeling;Molecular;Molecular Conformation;molecular dynamics;mutant;Mutation;mutation screening;next generation;novel;novel therapeutics;particle;Pathway interactions;Pattern;Persons;Pharmaceutical Preparations;Physics;Play;pressure;Proteins;Protocols documentation;public health relevance;Publications;Resistance;Resolution;response;Role;Sampling;simulation;Solvents;structural biology;Structure;System;Techniques;Therapeutic;Thermodynamics;Time;tool;Viral;Viral Proteins;Water;Work

PROJECT_TITLE: Mechanisms of HIV fitness and drug resistance inferred from high-resolution molecular dynamics and sequence co-variation models


PHR: Project Narrative: Diseases such as cystic fibrosis, hypogonadotropic hypogonadism, idiopathic lung fibrosis and retinitis pigmentosa result from improper biogenesis of mutant membrane proteins and a breakdown of the cell’s innate protein quality control mechanisms. Our overall goal is to understand how ER associated Hsp70 and Hsp40s facilitate the biogenesis, quality control, and maintenance of membrane proteins that perform essential cellular functions and are mutated in recessive (cystic fibrosis) and dominant (interstitial lung disease, retinitis pigmentosa) protein misfolding disease. Mechanisms identified will be targets for development of therapies that can treat this devastating set of diseases.

PI_NAMEs: CYR, DOUGLAS M (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Adopted;Amyloid;ATP phosphohydrolase;ATP-Binding Cassette Transporters;Attention;Autophagocytosis;Autophagosome;Benign;Binding;Biochemical;Biogenesis;Biological Assay;Biosynthetic Proteins;Blindness;Cell Physiology;Cell Survival;Cells;Client;Complex;conformer;Cystic Fibrosis;Cytoplasm;Cytosol;Data;Detergents;Diameter;Disease;Distal;Docking;Endoplasmic Reticulum;Ensure;Event;Exhibits;Experimental Designs;experimental study;Face;farnesylation;G-Protein-Coupled Receptors;Goals;Health;Human;human disease;Image;Induction of Apoptosis;Inferior;Inherited;Intermediate resistance;Interstitial Lung Diseases;Kinetics;Klinefelter's Syndrome;Length;Light;live cell imaging;Location;lysosomal proteins;lysosome membrane;Lysosomes;Maintenance;man;Membrane;Membrane Protein Traffic;Membrane Proteins;meter;Microtubules;misfolded protein;Missense Mutation;Molecular Chaperones;Motility;Movement;multicatalytic endopeptidase complex;mutant;Mutate;non-Native;Paint;Peptides;Phosphatidylinositols;Phosphotransferases;Poison;polypeptide;premature;prevent;Process;protein aggregation;protein degradation;protein folding;protein misfolding;Proteins;Proteome;proteotoxicity;Pulmonary Fibrosis;Quality Control;receptor;receptor function;recruit;Resistance;restraint;Retinitis Pigmentosa;Role;screening;Series;Shapes;Side;Site;Surface;System;Testing;therapy development;Thermodynamics;Triage;Tubular formation;ubiquitin-protein ligase;WD Repeat;Work;Yeasts

PROJECT_TITLE: Hsp40 and Hsp70 in Membrane Protein Triage

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Cancer;Clinical Research;Cost Effectiveness Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative Early stage oral cancers and precancers are currently under-detected, representing missed opportunity to improve the poor outcomes of oral cancer. While screening with conventional visual-tactile examination is limited in accuracy, artificial intelligence-assisted precision diagnostics could shift the cancer prevention paradigm toward screening for the broader population if enabling reliable triage of oral lesions for risk-based management. The proposed disease simulation model will evaluate the benefits and harms of harnessing these devices and precision treatment thresholds, guiding translation toward cancer control.

PI_NAMEs: KANG, STELLA  (contact)

PROGRAM_OFFICER_NAME: OKI, NOFFISAT

PROJECT_TERMS: Adult;Affect;Alcohol consumption;American;Appearance;Artificial Intelligence;aspirate;Benign;Biopsy;Cancer Control;Cancer Detection;cancer prevention;Cancerous;Carcinoma;Caring;Categories;Cells;Characteristics;Clinical;clinical application;clinical care;clinical decision-making;clinical risk;clinical translation;Complex;Computer Vision Systems;Computers;Consultations;cost;cost effective;cost effectiveness;curative treatments;Cytology;Cytopathology;Data;Decision Aid;Decision Making;Decision Modeling;Detection;Devices;Diagnosis;Diagnostic;Diagnostic Equipment;Diagnostic Imaging;diagnostic screening;diagnostic strategy;Diagnostic tests;Disease;disease model;disorder risk;Dysplasia;Early Diagnosis;Early identification;economic evaluation;economic outcome;Effectiveness;Goals;Health;Health Benefit;High Prevalence;high risk;Histologic;Image;improved;improved outcome;Incidence;Intraepithelial Neoplasia;Lesion;Longitudinal cohort study;longitudinal dataset;Machine Learning;Malignant - descriptor;malignant mouth neoplasm;Malignant neoplasm of pharynx;Malignant Neoplasms;Methods;Mild Dysplasia;Modeling;models and simulation;mortality risk;mouth squamous cell carcinoma;National Center for Advancing Translational Sciences;National Institute of Dental and Craniofacial Research;new technology;Optics;Oral;oral care;Oral Diagnosis;oral diagnostics;Oral Examination;oral lesion;Oral Medicine;oral premalignancy;Oral Stage;Organ;Outcome;overtreatment;Pathway interactions;Patients;Performance;personalized diagnostics;personalized management;Persons;point of care;Population;Precision therapeutics;premalignant;premature;prevent;Procedures;Quality of life;Risk;Risk Assessment;Risk Factors;risk stratification;Role;scalpel;Science;screening;Screening for Oral Cancer;screening guidelines;Specialist;Structure;Tactile;Testing;Tissues;Tobacco use;tool;Translating;translational diagnostics;Translations;Triage;United States National Institutes of Health;usability;Visual;Visualization;Work

PROJECT_TITLE: Optimizing Oral Cancer Screening and Precision Management of Potentially Malignant Oral Lesions

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Endocrine Disruptors;Genetics;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Social Determinants of Health

ORG_CITY: AUSTIN

ORG_NAME: VIVOVERSE, LLC

PHR: Product safety profiling, of which developmental and reproductive toxicology (DART) testing is an important component, is necessary to determine and continually ensure safe dosage or exposure levels of every chemical that comes into contact with humans. Toxicity testing is mostly done in genetically inbred mammals such as rats and rabbits, but public and regulatory pressure has led to directives eliminating the use of animals in safety testing where possible. In this proposal, we will develop a DART assay using genetically different wild strains of a microscopic soil worm, C. elegans, to provide a faster, cheaper, and more ethical alternative to testing on mammals, and investigate population-wide differences in responses to hazardous chemicals.

PI_NAMEs: HEGARTY, EVAN  (contact)

PROGRAM_OFFICER_NAME: RAVICHANDRAN, LINGAMANAIDU V

PROJECT_TERMS: Adolescent;Adult;age related;analysis pipeline;Animal Model;Animal Testing;Animal Testing Alternatives;Animal Welfare;Animals;automated analysis;Biological Assay;Biological Sciences;Body measure procedure;Caenorhabditis elegans;Case Study;Categories;Cell Line;Chemicals;Classification;Collection;Communities;cost;cost effective;Data;Databases;Development;developmental toxicity;Devices;Dimensions;dosage;Dose;Embryo;Embryonic Development;Ensure;environmental justice;Environmental Risk Factor;Ethics;Exposure to;Fishes;Genetic;Genetic Predisposition to Disease;Genetic Variation;Geography;Germ Lines;Goals;Guidelines;Hazardous Chemicals;Health;high resolution imaging;high throughput screening;Human;Image;Image Analysis;imaging platform;Immobilization;improved;in silico;in utero;In Vitro;in vivo;in vivo evaluation;Inbreeding;Industry;inorganic phosphate;Intestines;Invertebrates;Laboratory culture;Length;Life;Mammals;manufacture;Mercury;Methods;Microfluidics;microphysiology system;Microscopic;model organism;Modeling;Modernization;Monitor;Motility;mutant;Nematoda;new chemical entity;next generation;novel;novel strategies;Organ;Organism;Oryctolagus cuniculus;Outcome;Pathway interactions;Pharmaceutical Preparations;Pharyngeal structure;Phase;Phenotype;Poison;Population;pressure;Procedures;Protocols documentation;Publishing;Qualifying;Rattus;Reproducibility;reproductive;Reproductive system;reproductive toxicity;Resolution;response;Risk;Risk Assessment;Safety;safety testing;social;Soil;Source;Spearman Rank Correlation Coefficient;Statutes and Laws;Study models;Surveys;System;Technology;Testing;Time;Toxic effect;Toxic Environmental Substances;toxicant;Toxicity Tests;Toxicology;treatment response;Variant;Vertebrates;Visualization;Vulnerable Populations;Weight;Whole Organism

PROJECT_TITLE: The Next-Generation Developmental and Reproductive Toxicology (DART) Assay using High-Content Analysis of Genetically Diverse C. elegans Populations


NIH_SPENDING_CATS: Aging;Digestive Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative Older individuals have a significantly elevated risk for organ dysfunction and mortality when exposed to trauma or injury. We will examine a previously unknown mechanism for the increased morbidity in aged individuals due to chronic leak of digestive enzymes from the bowel into the systemic circulation and tissues, resulting in gradual but inexorable organ dysfunction with age. We propose and test a new translatable approach to block leaking digestive enzymes originating from the bowel and thereby reduce the high sensitivity to trauma in the old.

PI_NAMEs: KISTLER, ERIK ;SCHMID-SCHOENBEIN, GEERT W. (contact)

PROGRAM_OFFICER_NAME: FLORES, ROBERTO L

PROJECT_TERMS: Acute;Address;Affect;Aftercare;Age;aged;Aging;aging population;Amylases;animal old age;Attenuated;attenuation;Blood Coagulation Disorders;blood pressure reduction;Brain Injuries;Carbohydrates;Cardiac Surgery procedures;Cardiovascular Surgical Procedures;Cause of Death;Cells;Characteristics;Chronic;Circulation;Clinical;Digestion;Enteral;enzyme activity;Enzyme Inhibitor Drugs;Enzymes;Epithelium;Event;Exposure to;Extracellular Matrix Degradation;Extracellular Matrix Proteins;FDA approved;Female;Food;Functional disorder;Gastrointestinal Surgical Procedures;Gastrointestinal tract structure;Gender;Hemorrhage;high risk;Human;Impairment;improved;Incidence;Individual;Infiltration;Inflammation;inhibitor;injured;Injury;Insulin Resistance;Intervention;intestinal barrier;Intestinal permeability;Intestines;Life;Lipase;Lipids;male;Matrix Metalloproteinases;Measurement;Measures;Mediating;Membrane;meter;Morbidity - disease rate;mortality;Mucins;novel strategies;Nucleotides;older patient;Older Population;Operative Surgical Procedures;Organ;organ growth;Outcome;Pancreas;Pathogenesis;Pathologic;Patients;Peptide Hydrolases;Perfusion;Peripheral;phase 2 study;Phase II Clinical Trials;Phase III Clinical Trials;phase III trial;Plasma Proteins;Probability;Process;Productivity;Proteins;Rattus;receptor;Research;Resistance;Respiratory distress;Risk;senescence;Sepsis;septic patients;Serine Protease;Shock;Site;Small Intestines;Source;stressor;Symptoms;systemic barrier;Testing;Time;Tissues;Trauma;trauma exposure;Vasoconstrictor Agents;Work

PROJECT_TITLE: Attenuation of Multiorgan Dysfunction after Shock in the Aged


NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Nutrition

ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE This project will explore a mechanism we have uncovering by which selenium exerts its biological effects in a mechanistically distinct from its ‘textbook’ role of producing selenoproteins. Our findings indicate that selenium can also donate its electrons to ubiquinol and that this is a rapid mechanism by which selenium can counter oxidative stress and restore electron transport chain activity, expanding what is known about selenium in biology. We will explore how this mechanism can protect against cell death in models for various disease contexts including heart attacks, mitochondrial disorders, and environmental toxin exposure.

PI_NAMEs: KIM, DOHOON  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Anabolism;Antioxidants;arm;Biological;Biology;Bypass;Cardiac Myocytes;Cardiovascular Physiology;Cell Death;Cell model;Cell Respiration;Cell Survival;Cells;Chronic;Clinical;CRISPR screen;Cytoprotection;Data;dietary supplements;Disease;disease model;Dose;electron donor;Electron Transport;Electrons;Functional disorder;Genes;Genetic;glutathione peroxidase;Health;Impairment;in vitro activity;in vivo;Intoxication;Intravenous;intravenous administration;Ischemia;Knockout Mice;Lipid Peroxidation;Mediating;Membrane;Metabolic;Micronutrients;Mitochondria;Mitochondrial Diseases;mitochondrial membrane;Modeling;Mus;Myocardial Infarction;Nerve Degeneration;novel;Oxidation-Reduction;Oxidative Stress;Oxidoreductase;Pathologic;Pathway interactions;Peptides;pharmacologic;Physiological;Production;Property;Quinones;Reaction;Role;Route;Selenite;Selenium;selenium deficiency;selenium poisoning;Selenocysteine;selenocysteine lyase;Selenomethionine;selenoprotein;Skin;Source;success;Sulfides;Supplementation;Testing;Textbooks;Therapeutic;Therapeutic Effect;thioredoxin reductase;Toxic effect;Toxic Environmental Substances;Trace Elements;ubiquinol;Ubiquinone

PROJECT_TITLE: Selenoprotein-independent biological roles for selenium in selenium deficiency and excess

STUDY_SECTION: NMHD

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


NIH_SPENDING_CATS: Cardiovascular;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Lung;Networking and Information Technology R&D (NITRD);Sleep Research

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Time-to-event outcomes are commonly encountered in diagnostic and therapeutic research for heart, lung, blood and sleep diseases, e.g. time to stroke. Because the popular hazard ratio measure does not provide a valid marginal causal effect interpretation, we propose to develop a comprehensive propensity score matching based restrict mean survival time estimation strategy and a software package for clinical researchers to tackle this complex causal inference problems in observational studies. We will also apply these methods to conduct a secondary data analysis on effectiveness of anticoagulant drugs using electronic medical record data.

PI_NAMEs: LU, BO  (contact)

PROGRAM_OFFICER_NAME: ANAYA, GABRIEL

PROJECT_TERMS: Accounting;Adopted;Algorithms;Anticoagulants;Area;Asthma;cardiovascular risk factor;Cardiovascular system;Cessation of life;Clinical;Clinical assessments;clinical diagnosis;Communities;Comparative Effectiveness Research;Complex;Computer software;Computerized Medical Record;Cox Proportional Hazards Models;Data;Data Analyses;data registry;Databases;design;Development;Diagnostics Research;Disease;Disparity;Drug usage;Effectiveness;effectiveness evaluation;Event;Funding Mechanisms;Gender;Goals;hazard;health disparity;Heart Diseases;Hematological Disease;Lung Diseases;Mean Survival Times;Measures;method development;Methodology;Methods;Modeling;mortality;Myocardial Infarction;National Heart, Lung, and Blood Institute;novel;Observational Study;Oral;Outcome;Outcome Measure;Patient-Focused Outcomes;Patients;Performance;Pharmaceutical Preparations;primary endpoint;Procedures;Race;Randomized;randomized trial;Reporting;Research;Research Methodology;Research Personnel;Research Project Grants;respiratory;Risk;Selection Bias;simulation;Sleep Disorders;Sleeplessness;Stratification;Stroke;Subgroup;Survival Analysis;Therapeutic;Therapeutic Effect;Therapeutic Research;Time;tool;treatment effect;treatment group;venous thromboembolism;Warfarin;Work

PROJECT_TITLE: Matched Design with Sensitivity Analysis for Observational Survival Data in Cardiovascular Patient Management using EMR Data

STUDY_SECTION: ASPB

STUDY_SECTION_NAME: Analytics and Statistics for Population Research Panel B Study Section[ASPB]


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

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: PROJECT NARRATIVE: Glioblastoma (GBM) is the most common malignant primary brain tumor and among the most lethal due to their recurrence and therapeutic resistance. These properties are associated with a GBM stem cell (GSC) fraction present within distinct microenvironmental niches of the tumor and we have identified the protein WDR5 as specifically essential for GSCs to grow and maintain stem-cell-like biology in GSC-rich niches of GBM tumors. The successful completion of this proposal will yield an understanding of the roles of WDR5 in GBM niche biology and an appraisal of the therapeutic efficacy of inhibiting WDR5 in GBM.

PI_NAMEs: HUBERT, CHRISTOPHER G (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: 3-Dimensional;Biology;Blood - brain barrier anatomy;Blood Vessels;blood-brain barrier penetration;Brain;Brain Neoplasms;cancer type;candidate validation;Cell Fraction;Cell Maintenance;Cell Proliferation;Cells;Chromatin;chromatin immunoprecipitation;Clinical;Combined Modality Therapy;Complex;confocal imaging;CRISPR/Cas technology;Data;Disease;Dose;embryonic stem cell;Epigenetic Process;Essential Genes;Evaluation;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Glioblastoma;Goals;Growth;Histones;Hypoxia;Immunohistochemistry;improved;in vivo;Individual;inhibitor;innovation;Intracranial Neoplasms;Label;Lysine;Maintenance;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Measures;Methodology;Methods;Methylation;Modeling;mouse model;Necrosis;Normal Cell;novel;novel strategies;novel therapeutic intervention;Nutrient;Organoids;Outcome;patient derived xenograft model;Patients;Pharmaceutical Preparations;pharmacologic;Population;pre-clinical;Pre-Clinical Model;prevent;Primary Brain Neoplasms;programs;promoter;Property;Proteins;Proto-Oncogenes;Radiation therapy;rational design;reconstruction;Recurrence;Research;Resistance;Resolution;Role;screening;self-renewal;senescence;Signal Transduction;Slice;Solid Neoplasm;spheroids;standard of care;stem;stem cell biomarkers;stem cell growth;stem cell proliferation;stem cell self renewal;stem cells;stem-like cell;stemness;Structure;System;Techniques;temozolomide;Testing;Therapeutic;therapeutic target;therapy resistant;Thick;transcriptome sequencing;Treatment Efficacy;tumor;Tumor Biology;tumor hypoxia;tumor microenvironment;tumorigenic;WD Repeat;Work

PROJECT_TITLE: Therapeutic Targeting of WDR5 in the Glioblastoma Perivascular Niche

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: Narrative This project will investigate genome-wide patterns of nascent transcription and histone methylation in mouse skin.

PI_NAMEs: LIS, JOHN T;TUMBAR, TUDORITA  (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Address;Adult;Affect;Biological Models;Biological Process;Biology;Cell Lineage;Cell Maintenance;Cell Physiology;Cell Separation;cell type;Cells;Chromatin;conditional knockout;Data;Development;Developmental Gene;Disease;Dissociation;Drug Design;Embryo;Embryonic Development;Enzymes;Epigenetic Process;Epithelium;Future;Gene Expression Regulation;gene repression;Gene Silencing;Gene Targeting;Genes;Genetic;Genetic Transcription;genome-wide;Genomic approach;Hair;Hair follicle structure;Heterochromatin;Histone H3;histone methylation;histone methyltransferase;histone modification;Histones;Homeostasis;Impairment;in vivo;inducible Cre;insight;Investigation;keratinocyte;Knock-out;Knockout Mice;Knowledge;liver development;Maps;Mediating;Messenger RNA;Methodology;Methods;Methyltransferase;Molecular;Morphogenesis;mouse genetics;mouse model;Mus;Natural regeneration;Normal tissue morphology;novel;Nuclear;pancreas development;Pathology;Pattern;pharmacologic;Physiological;Polymerase;Population;Post-Transcriptional Regulation;posttranscriptional;Productivity;promoter;prototype;recruit;Regulation;Repression;RNA;RNA Polymerase II;RNA Probes;RNA Stability;Role;Running;Skin;skin organogenesis;Stratification;Therapeutic Uses;Time;Tissue Engineering;tissue mapping;tissue stem cells;Tissues;tool;Transcript;Transcription Elongation;Transcription Initiation;transcriptome sequencing;Transferase;Work;wound healing

PROJECT_TITLE: Tissue biology studies of histone modification, nascent transcription, and post-transcription regulation


NIH_SPENDING_CATS: Biotechnology;Genetics;Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Rehabilitation;Spinal Cord Injury;Traumatic Head and Spine Injury

PHR: Narrative We propose to study the potential crucial roles of transcriptional factor ZNF362 and cytoskeletal non- muscle myosin IIA & IIB genes in suppressing axon regeneration after spinal cord injury and to develop highly effective systemic therapies for CNS injury in adult mammals.

PI_NAMEs: LI, SHUXIN  (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Actomyosin;Adult;antagonist;Axon;axon growth;axon injury;axon regeneration;axonal degeneration;Binding;cell growth;central nervous system injury;Cervical;Chronic;Clinical;Clinical Trials;combinatorial;Combined Modality Therapy;conditional knockout;Cytoskeletal Proteins;Cytoskeleton;design;disabled;Dorsal;effective therapy;Environment;Failure;Gene Targeting;Genes;Genetic;Growth;Growth Cones;Individual;inhibitor;injury and repair;Knockout Mice;Lesion;Locomotor Recovery;Mammals;Microfilaments;Microtubules;Modeling;Molecular Target;Motor;Mus;mutant;Myosin Type II;Natural regeneration;neuronal growth;Neuronal Injury;Neurons;neurotransmission;non-muscle myosin;Nonmuscle Myosin Type IIA;Nonmuscle Myosin Type IIB;novel;Paralysed;Pathway interactions;Patients;Peptides;pharmacologic;Pilot Projects;Population;Proteins;Recovery;Recovery of Function;regenerative approach;regenerative treatment;repaired;Rodent;Role;safety assessment;Sensory;Signal Pathway;Signal Transduction;Spinal Cord;Spinal Cord Contusions;Spinal cord injury;Synapsins;Systemic Therapy;targeted agent;Therapeutic;therapeutic gene;Thoracic spinal cord structure;Tracer;transcription factor;Translating;translational study;Work;Zinc Fingers

PROJECT_TITLE: Identifying novel regenerative treatments for CNS injury in adult mammals

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


NIH_SPENDING_CATS: Cancer

ORG_CITY: HOUSTON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE This project will investigate how a subset of surface glycosphingolipids regulate the localization and function of KRAS on the inner plasma membrane. KRAS operates as a molecular switch that regulates cell proliferation, survival and differentiation. Unraveling the novel mechanisms underpinning the role of glycosphingolipids will have therapeutic applications since constitutively activated KRAS must be localized to the plasma membrane in the correct lipid environment in order to function.

PI_NAMEs: GORFE, ALEMAYEHU A.;HANCOCK, JOHN F (contact);LIU, JUNCHEN

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: aerobic glycolysis;Anabolism;Animal Model;Apoptosis;Binding;Biological Models;Biophysics;Biosensor;C-terminal;Cancer Model;Carrier Proteins;Cell membrane;Cell Proliferation;Complex;Coupled;Couples;Coupling;Dependence;Electron Microscopy;Endoplasmic Reticulum;Environment;Enzymes;Esters;experimental study;Feeds;Genetic;genetic approach;Glucose;Glycolysis;Glycosphingolipids;Grant;Growth Factor Receptors;GTP Binding;Guanosine Triphosphate Phosphohydrolases;high resolution imaging;imaging approach;In Vitro;in vivo;inhibitor;insight;interdisciplinary approach;KRAS oncogenesis;KRAS2 gene;Lead;Lecithin;Link;lipid transport;Lipids;Lysine;Malignant neoplasm of lung;MEKs;Membrane;Membrane Biology;Membrane Lipids;Membrane Proteins;Metabolic;Metabolism;Methods;Molecular;molecular dynamics;mouse model;Mus;nanocluster;nanoscale;Nanostructures;Noise;novel;Oncogenic;Pancreas;pancreatic cancer model;Pathologic;Pathway interactions;pharmacologic;Phosphatidylethanolamine;phosphatidylinositol 4-phosphate;Phosphatidylserines;Phospholipids;Proteins;Proteolipids;reconstitution;recruit;Regulation;Role;Signal Pathway;Signal Transduction;Site;Specificity;Structure;Surface;synergism;synthetic enzyme;Testing;Therapeutic;Transmembrane Transport;transmission process;tumorigenesis;Warburg Effect

PROJECT_TITLE: Regulation of KRAS plasma membrane targeting by defined glycosphingolipids.


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

ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Therapies that disrupt immune evasion through the PD-1 or CTLA-4 pathways have shown remarkable efficacy yet fail in many patients, likely due to additional mechanisms that are yet to be defined. This proposal will investigate how epigenetic silencing of the repetitive genome drives immune escape in cancer cells, and will specifically explore the role of the epigenetic repressor, SETDB 1, in silencing transposable elements and immune genes in melanoma. A deeper understanding of these mechanisms could ultimately yield new biomarkers and epigenetic therapies capable of selectively enhancing the efficacy and scope of immunotherapy for melanoma and other cancer types.

PI_NAMEs: GRIFFIN, GABRIEL K. (contact)

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: 3-Dimensional;Advisory Committees;Antigens;Area;Automobile Driving;Binding;Biological Markers;Biological Response Modifiers;Burn injury;Cancer Biology;cancer cell;cancer genome;cancer immunotherapy;cancer type;career;career development;Cell division;Chromatin;Chromatin Remodeling Factor;clinical training;Communication;CTLA4 gene;Dana-Farber Cancer Institute;Data;derepression;Detection;Development;DNA Transposable Elements;Elements;Enhancers;Epigenetic Process;epigenetic regulation;epigenetic silencing;epigenetic therapy;epigenomics;Evolution;experience;Faculty;Future;Gene Activation;Genes;Genetic Transcription;Genome;Genomics;Goals;Hematopathology;Hospitals;Human;Immune;immune activation;immune checkpoint blockade;Immune Evasion;immunoregulation;Immunotherapy;in vivo;insight;International;Knock-out;Knowledge;Laboratories;Leadership;Lewis Lung Carcinoma;Lewis lung carcinoma cell;loss of function;lung cancer cell;Malignant Neoplasms;Maps;Mediating;medical schools;meetings;melanocyte;Melanoma;Mentors;Modeling;Mus;Nature;neoplastic cell;novel;Pathology;Pathway interactions;Patients;PAX3 gene;Physicians;Play;professor;programmed cell death protein 1;programs;promoter;Proteins;recruit;Regulation;Research;response;restoration;Role;Scientist;SETDB1 gene;Signal Transduction;skills;System;Testing;Training;Training Programs;transcription factor;Transcriptional Activation;Transcriptional Silencer Elements;tumor;Tumor Immunity;tumor immunology;Woman;Work

PROJECT_TITLE: Harnessing the repetitive genome for cancer immunotherapy

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]