NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Hematology;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Pediatric;Pediatric Cancer;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health;Telehealth

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

ORG_STATE: CA

PHR: PROJECT NARRATIVE This study will evaluate the ability of a targeted eHealth parent-directed intervention to reduce the burden of cancer survivorship by improving psychosocial and behavioral outcomes in the underserved population of childhood leukemia and lymphoblastic lymphoma survivors. We anticipate that leveraging digital health solutions will produce an effective, scalable therapy that overcomes key barriers to follow-up care and is easily integrated into care delivery.

PI_NAMEs: PATEL, SUNITA K (contact)

PROGRAM_OFFICER_NAME: ADAMS, LYNN S

PROJECT_TERMS: Acute Lymphocytic Leukemia;Address;Adult;adverse outcome;Award;behavioral outcome;Brain;California;Cancer Burden;Cancer Center;Cancer Survivor;Cancer Survivorship;cancer therapy;care delivery;Caring;Central Nervous System;Child;Child Behavior;Childhood Brain Neoplasm;childhood cancer survivor;Childhood Leukemia;Cities;cognitive function;comparative efficacy;design;Development;Diagnosis;digital health;Disparity;E-learning;Education;educational atmosphere;Educational Intervention;Educational process of instructing;effective therapy;effectiveness evaluation;eHealth;Eligibility Determination;Enrollment;Environment;experience;Family;Feedback;follow-up;functional outcomes;Goals;Habits;Health;health care delivery;Health Disparities Research;health disparity;Health Insurance Portability and Accountability Act;health related quality of life;Health Technology;high risk;Impairment;improved;innovation;insight;Intervention;intervention program;Language;Late Effects;Latino;Learning;learning strategy;leukemia;leukemia/lymphoma;Link;Long-Term Care;Los Angeles;low socioeconomic status;Lymphoblastic Lymphoma;Malignant Childhood Neoplasm;Medical center;medically underserved population;meetings;Monitor;Multimedia;Neurocognition;Neurocognitive;Neuropsychological Tests;online resource;Online Systems;Outcome;outcome disparities;parental involvement;Parents;Patient Self-Report;Patients;Pediatric Hospitals;Pediatric Oncologist;Performance;Persons;Phase;pilot trial;Population;prevent;programs;psychosocial;psychosocial outcome;randomized, clinical trials;Randomized, Controlled Trials;Recommendation;Research;Risk;routine care;Schedule;Schools;Shapes;Site;skills;social;sociodemographic group;Socioeconomic Status;Spanish/English;Special Education;standard care;stress management;success;Survivors;Technology;telehealth;Test Result;Testing;Time;tool;Toxic effect;Training;Travel;treatment as usual;Treatment Side Effects;Underserved Population;Unemployment;uptake;Videoconferencing;web site

PROJECT_TITLE: Leveraging Digital Health Solutions to Reduce Learning and Functional Disparities in Children with Cancer


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Hematology;Infectious Diseases;Osteoporosis;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: INDIANAPOLIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ORTHOPEDICS

ORG_FIPS: US

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE  The COVID-19 pandemic has taken the lives of millions, but millions more have survived infection, revealing a large number of effects on the human body, but whether these effects go away with time remains unknown. One understudied area is how contracting COVID-19 impacts the skeleton which is particularly concerning for older people that are more susceptible to both COVID-19 and bone loss associated with osteoporosis. The studies in this application will examine how bone loss changes based on age at the time of infection and the severity of COVID-19 disease, and will demonstrate how cells that breakdown bone, function to decrease bone mass.

PI_NAMEs: AWOSANYA, OLATUNDUN DUPE (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: 2019-nCoV;Age;Age Months;aged;aging population;Area;Autopsy;Blood Platelets;Body System;Body Weight;bone;bone loss;Bone Marrow;bone mass;bone metabolism;Bone Resorption;bone turnover;Brain;Cardiac;Cells;Cessation of life;Clinical;cohort;combat;Conditioned Culture Media;Contracts;COVID-19;COVID-19 complications;COVID-19 impact;COVID-19 pandemic;COVID-19 patient;COVID-19 severity;CXCL10 gene;cytokine;cytokine release syndrome;Data;Disease;disease model;Dose;Epidemic;Euthanasia;Exhibits;experience;Femur;General Population;Goals;Growth Factor;Health;Heart;high risk;Histologic;Homeostasis;Human body;IL17 gene;Infection;Inflammatory;Interleukin-1 beta;Interleukin-6;K-18 conjugate;Laboratories;Lead;Light;Lung;Megakaryocytes;Monitor;mortality;mouse model;Mus;Musculoskeletal;Musculoskeletal System;old mice;Older Population;Organ;Osteitis;osteoclast progenitor;Osteoclasts;Osteoporosis;OSTF1 gene;Patients;Platelet Count measurement;Population;post SARS-CoV-2 infection;Posture;Predisposition;Reporting;SARS-CoV-2 infection;SARS-CoV-2 negative;Serum;severe COVID-19;Severities;Severity of illness;skeletal;Skeleton;substantia spongiosa;Surface;System;Testing;Thrombophilia;Thrombopoietin;Thrombus;Time;Titrations;TNF gene;TNFSF11 gene;Transgenic Mice;treatment strategy;Vaccines;Viral Load result

PROJECT_TITLE: Impacts of SARS-CoV-2 Infection and Age on Musculoskeletal Health


ADMINISTERING_IC: MH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Mental Health;Mental Illness;Pediatric;Rehabilitation;Serious Mental Illness;Social Determinants of Health

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Childhood adversity is associated with higher risk of youth-onset depression, disruptions in cognitive and learning processes, and poor response to front-line depression treatments. Poor treatment response in adversity-exposed youths is largely unexplained, and the proposed research will be the first to examine how adversity and related impairments in learning processes (i.e., sub-processes of cognitive control) influence the acquisition of therapy skills, a primary treatment process in evidence-based psychotherapies. The research strategy presents a critical first step in identifying how childhood adversity impacts treatment effectiveness, and it has the potential to inform intervention research aimed at tailoring and optimizing depression interventions in this vulnerable youth population.

PI_NAMEs: VAUGHN-COAXUM, RACHEL  (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: Adolescence;Affective;Age;anti-depressive agents;Award;Basic Science;Behavior assessment;biobehavior;burden of illness;career;career development;Caregivers;Cessation of life;Characteristics;Child;child depression;Childhood;childhood adversity;Clinical;Cognitive;cognitive control;cognitive process;Cognitive Therapy;computerized;Data;Depressed mood;depressive symptoms;deprivation;Development;Dimensions;Educational process of instructing;Effectiveness;Emotional;Emotions;Evaluation;evidence base;Exposure to;Feedback;flexibility;follow-up;Goals;Health;high risk;Impairment;innovation;Intervention;intervention refinement;Intervention Studies;Interview;Investigational Therapies;Joints;Knowledge;Learning;Learning Skill;Life;longitudinal design;Measures;Mediating;Mental Depression;Mentored Patient-Oriented Research Career Development Award;Mentors;Modeling;neglect;novel;novel strategies;Outpatients;Parents;Pathology;Pathway interactions;Patients;peer;personalized therapeutic;Population;Poverty;Primary Care;Process;Psychiatry;Psychological reinforcement;Psychopathology;Psychophysiology;Psychotherapy;Questionnaires;Recording of previous events;Recovery;recruit;Regulation;remote assessment;Reporting;Research;Resources;response;Response to stimulus physiology;Reversal Learning;Risk;Science;skill acquisition;skills;social deprivation;Testing;Training;translational research program;treatment comparison;Treatment Effectiveness;Treatment outcome;treatment research;treatment response;treatment risk;United States National Institutes of Health;Universities;Update;violence exposure;Visit;Youth

PROJECT_TITLE: The Influence of Childhood Adversity on Psychotherapy Skill Acquisition in Adolescent Depression

STUDY_SECTION: CPDD

STUDY_SECTION_NAME: Child Psychopathology and Developmental Disabilities Study Section[CPDD]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Prevention;Rare Diseases

ORG_CITY: CHICAGO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it offers novel molecular analysis capabilities for detecting epigenetic alterations in various sources of DNA from limited tissue biopsies and liquid biopsies. The validation of this technique will provide opportunities to cancer research that have been limited by technology and the availability of limited clinical biospecimens, e.g., multi-omics studies and liquid biopsy-based early cancer detection. Therefore, the proposed research is relevant to the NIH's mission, in particular to the RFA- CA-21-004 that pertains to novel technologies and molecular analysis for clinical cancer research that will help reduce the morbidity and mortality of cancer.

PI_NAMEs: CHIU, BRIAN C-H (contact);ZHANG, WEI

PROGRAM_OFFICER_NAME: SORG, BRIAN S

PROJECT_TERMS: Acceleration;Achievement;Address;Aftercare;age group;anti-cancer research;base;biobank;Biological Assay;Biological Markers;Biological Process;biomarker discovery;Biopsy;bisulfite;bisulfite sequencing;Blood;Body Fluids;Cancer Biology;Cancer Detection;cancer diagnosis;Cancer Diagnostics;cancer epidemiology;Cancer Patient;cancer type;cell free DNA;Cells;chemical stability;Clinic;Clinical;clinical application;Clinical Oncology;Colon Carcinoma;cost efficient;CpG dinucleotide;Cytosine;design;Detection;Development;Diagnosis;Diagnostic Procedure;DNA;DNA Library;DNA methylation profiling;Early Diagnosis;Ensure;Environment;epidemiology study;Epigenetic Process;FDA approved;Frequencies;Funding;future implementation;Gene Expression Regulation;Genetic;Genomic DNA;Genomics;Goals;Guanine + Cytosine Composition;high risk population;Human;Human Genome;improved;Individual;innovation;innovative technologies;Investigation;large cell Diffuse non-Hodgkin's lymphoma;liquid biopsy;Machine Learning;Malignant neoplasm of liver;Malignant neoplasm of pancreas;Malignant Neoplasms;Methylation;minimally invasive;Mission;Modification;Molecular;Molecular Analysis;Molecular Profiling;Molecular Target;Monitor;Morbidity - disease rate;mortality;multidisciplinary;Multiple Myeloma;multiple omics;nano;new technology;Newly Diagnosed;next generation sequencing;noninvasive diagnosis;novel;Pathogenesis;Patient Monitoring;Patients;Plasma;Plasma Cells;Population Study;Prevalence;Primary Neoplasm;Procedures;Prognosis;prospective;Public Health;recruit;Research;Residual Neoplasm;Resistance;Resolution;RNA;Role;Sampling;screening;Screening for cancer;sex;Source;Specificity;Specimen;success;Systems Biology;Techniques;Technology;Testing;Tissues;tool;tumor;Tumor Bank;tumor DNA;tumor heterogeneity;Tumor Tissue;United States National Institutes of Health;Validation;whole genome

PROJECT_TITLE: A highly sensitive linear amplification based DNA methylation profiling technique for clinical cancer research


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Aphasia;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Machine Learning and Artificial Intelligence;Neurodegenerative;Neurosciences;Rehabilitation

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: In our previous K24 cycle, Dr Gorno Tempini expanded and formalized her POR mentoring and undertook novel research into the susceptibility of the language system to neurodegeneration. This proposed renewal will train the next generation of clinician scientists in language disorders and neurodegenerative disease through didactics, group, and one on one mentoring sessions. The research project will develop novel automated and imaging measures of speech production impairments in PPA.

PI_NAMEs: GORNO TEMPINI, MARIA LUISA  (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Acoustics;Aging;Air;Algorithms;Alzheimer's Disease;Anatomy;Anomia;Anterior;Aphasia;Area;Articulation;Atrophic;Attention;automated analysis;automated speech recognition;Autopsy;Basic Science;Behavior Therapy;Behavioral;Biological Markers;biomechanical test;Biomechanics;Brain;brain circuitry;brain health;Caring;Cessation of life;Characteristics;Clinical;Clinical Sciences;Cognitive;cognitive neuroscience;cohort;Communication;constriction;Data;Data Science;Dementia;Diagnosis;Differential Diagnosis;Disease;Disease Progression;Early Diagnosis;Enrollment;equity, diversity, and inclusion;Evaluation;experience;Faculty;Frontotemporal Lobar Degenerations;Functional Imaging;Future;Goals;Grant;Image;Impairment;improved;innovation;interest;Knowledge;Laboratories;Language;Language Disorders;Leadership;Learning;Left;Machine Learning;machine learning algorithm;Magnetic Resonance Imaging;Measurement;Measures;Memory;Mentors;Methodology;Methods;Molecular;molecular pathology;Monitor;Motor;Movement;Nerve Degeneration;neural;Neuroanatomy;Neurodegenerative Disorders;neuroimaging;Neurologic;Neurologist;Neurology;Neurosciences;next generation;novel;Outcome Measure;Pathologic;Pathologist;Pathology;patient oriented research;Patients;Pattern;Peer Review;Pharmacologic Substance;Pharmacological Treatment;Phenotype;phonology;Positioning Attribute;Postdoctoral Fellow;predictive tools;Predisposition;Primary Progressive Aphasia;Production;Progressive Aphasias;Publications;Reading;real-time images;Research;Research Personnel;Research Project Grants;Resources;response;Sampling;Scientist;Semantics;Severities;shape analysis;Shapes;Site;Speech;Speech Acoustics;Speech Disorders;Speech Sound;structural imaging;Structure;success;Supervision;Syndrome;System;Talents;tau Proteins;Techniques;Technology;Time;Tissues;Training;training opportunity;Training Programs;Translational Research;treatment response;treatment trial;Universities;Update;Variant

PROJECT_TITLE: Training program in the neurology of language and neurodegenerative aphasias

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: HOUSTON

ORG_NAME: VATHES INC.

ORG_STATE: TX

PHR: The project will systematize and disseminate data pipeline designs from leading neuroscience projects imple mented in the open-source DataJoint framework. The designs string together steps for data collection and analysis and integrate diverse informatics tools for neurophysiology experiments. This work will further dis seminate the use of DataJoint in neuroscience, streamline integration of new analysis methods and informatics tools, and provide starting points for new projects.

PI_NAMEs: YATSENKO, DIMITRI  (contact)

PROGRAM_OFFICER_NAME: TRZCINSKI, NATALIE KATHERINE

PROJECT_TERMS: Acceleration;Adopted;Adoption;Algorithms;Architecture;Atlases;Behavior;Books;Brain;BRAIN initiative;Calcium;Cells;Classification;Cloud Service;Collaborations;Collection;complex data;computerized data processing;Data;Data Analyses;Data Collection;data ecosystem;data integrity;data modalities;data pipeline;data sharing;data tools;design;diverse data;E-learning;Electrodes;Electron Microscopy;Electronics;Electrophysiology (science);experimental study;Fostering;graphical user interface;Guidelines;hackathon;Image;imaging Segmentation;informatics tool;International;Learning;Libraries;light microscopy;Methods;neurophysiology;Neurosciences;Nomenclature;online resource;Ontology;open source;optogenetics;Output;Persons;Positioning Attribute;Problem Sets;Research;Resource Informatics;Sampling;Scientist;Sensory;Sorting;System;Techniques;tool;transcriptomics;Transgenic Organisms;Virus;Visualization;Work

PROJECT_TITLE: DataJoint Pipelines for Neurophysiology


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Drug Abuse (NIDA only);Neurosciences;Nutrition;Substance Misuse

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Project Narrative How homeostatic setpoints are determined and represented in the brain remain unanswered questions for all motivated behaviors. In this proposed study, using mating induced resetting of protein intake target in Drosophila as a model system, we aim to elucidate the circuit and molecular substrates mediating the determination of homeostatic setpoint. This study should provide insights into the fundamental principles for the organization and modulation of homeostatic setpoint for motivated behaviors.

PI_NAMEs: LIU, QILI  (contact)

PROGRAM_OFFICER_NAME: DAVID, KAREN KATE

PROJECT_TERMS: Action Potentials;Address;Adult;Animals;Astrocytes;Behavior;Behavior assessment;behavior measurement;behavioral study;Biological Models;Brain;Calcium Signaling;Cell Communication;Cells;Consumption;Dedications;Dendrites;dietary;Drosophila genus;egg;Electrophysiology (science);feeding;Feeds;Female;fly;Food;Fortified Food;Functional Imaging;Future;Genetic;genetic analysis;Genetic Screening;Goals;Growth;Hour;Human;Hunger;Immunohistochemistry;Impairment;in vivo imaging;insight;Insulin;Insulin Receptor;insulin signaling;Intake;interdisciplinary approach;Investigation;Macronutrients Nutrition;Measures;Mediating;Membrane;Membrane Potentials;model organism;Modeling;Molecular;Monitor;motivated behavior;neural circuit;Neuroglia;neuronal circuitry;Neurons;novel;Partner in relationship;patch clamp;Pathway interactions;Peptides;Physiological;pointed protein;pregnant;Process;Production;protein intake;Proteins;Rest;RNA interference screen;sensor;Set protein;sex;Signal Transduction;Sleep;Social Interaction;Starvation;Synapses;System;Testing;tool;Translating;translating ribosome affinity purification and RNA-sequencing;Water

PROJECT_TITLE: Mechanism and Modulation of the homeostatic setpoint for protein feeding


FUNDING_MECHANISM: SBIR-STTR RPGS

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

ORG_CITY: HOWARD BEACH

ORG_NAME: GISMO THERAPEUTICS, INC.

ORG_STATE: NY

PHR: PROJECT NARRATIVE Alzheimer’s disease is a progressive neurologic disease of the brain leading to the irreversible loss of memory and cognitive performance which become severe enough to impede social or occupational functioning. This chronic, debilitating disorder results in a devastating burden on the families and caregivers of patients, with the rising costs of care in the United States exceeding $170 billion a year. The goal of this SBIR proposal is to develop a novel and orally effective small molecule for the treatment of Alzheimer’s disease. The drugs described in this proposal act via a novel and highly differentiated mechanism of action and are postulated to exhibit an improved efficacy / safety risk compared to the current standard of care.

PI_NAMEs: GREGOR, PAUL  (contact)

PROGRAM_OFFICER_NAME: MARTIN, ZANE

PROJECT_TERMS: 3xTg-AD mouse;AD transgenic mice;Address;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Amyloid;Amyloid beta-Protein;amyloid peptide;Amyloidosis;Award;Biochemical;Biochemical Pathway;Biological Assay;Biological Availability;Blinded;Bone Marrow;Brain;Brain Diseases;Canis familiaris;Cardiovascular system;care costs;Caregivers;Central Nervous System;chemical property;Chronic;Cognitive;cognitive performance;Conscious;Data;Development;Disease;Dose;Drug Kinetics;drug-like compound;efficacy evaluation;Exhibits;family burden;Formulation;glycosaminoglycan receptor;Glycosaminoglycans;Goals;Half-Life;Heparitin Sulfate;Hepatocyte;Hippocampus;Hour;Human;hyperphosphorylated tau;improved;In Vitro;inhibitor;Kentucky;Knock-in;Memory Loss;Metabolic;method development;Methods;micronucleus;Microsomes;Modeling;Monkeys;mouse model;Mus;Mutagenicity Tests;Nerve Degeneration;Nervous System Disorder;neuropathology;new chemical entity;novel;Occupational;old mice;Oral;Pathogenesis;Patients;Peptides;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phase;Phase I Clinical Trials;physical property;Plasma;polysulfated glycosaminoglycan;Positioning Attribute;pre-clinical;preclinical development;preclinical evaluation;preclinical study;prion-like;Process;programs;Property;protein aggregation;Rattus;Recovery;respiratory;Risk;Rodent;Safety;safety assessment;scale up;Series;Small Business Innovation Research Grant;small molecule;social;standard of care;tau interaction;tau Proteins;Tauopathies;Testing;Therapeutic;Toxic effect;Toxicokinetics;Toxicology;Transgenic Mice;transgenic model of alzheimer disease;Transgenic Organisms;United States;Universities;Validation;Work;β-amyloid burden

PROJECT_TITLE: Amyloid-Beta and Tau/Glycosaminoglycan Dual Inhibitor for Alzheimer's Disease


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Human Genome;Pediatric;Precision Medicine

ORG_CITY: LOS ANGELES

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Epigenes are genes that encode proteins that can affect chromatin’s spatial organization and regulate cell-type specific transcription. The role of these genes in programming early developmental cell-fate transitions can be best modeled in complex systems such as mouse development. We developed mouse models of epigene mutations in the histone acetyltransferase genes in order to understand the multi-organ effects of KAT6A and KAT6B across early development.

PI_NAMEs: ARBOLEDA, VALERIE A (contact)

PROGRAM_OFFICER_NAME: MIROCHNITCHENKO, OLEG

PROJECT_TERMS: Acetylation;Acetyltransferase;adult stem cell;Affect;Animal Model;Area;associated symptom;ATAC-seq;autism spectrum disorder;Automobile Driving;Barbering;Body System;bone;Brain;Cardiac;cell type;Cells;Child;Childhood;Chromatin;Cleavage Under Targets and Release Using Nuclease;Clinical;clinical phenotype;Complex;conditional mutant;Congenital Heart Defects;design;Development;Developmental Delay Disorders;Developmental Process;diagnostic value;Diarrhea;Disease;Dissection;DNA;early childhood;effectiveness validation;Embryo;Embryonic Development;Enterobacteria phage P1 Cre recombinase;Epigenetic Process;epigenome;epigenomics;exome sequencing;Exons;Eye;flexibility;Fluorescent in Situ Hybridization;Gastrointestinal tract structure;gene function;Genes;Genetic;Genetic Diseases;genetic disorder diagnosis;Genetic Predisposition to Disease;Genetic Transcription;Genomic Segment;Genotype;Germ-Line Mutation;Goals;Health;Heart;Heterozygote;Histone Acetylation;histone acetyltransferase;Histones;Homologous Gene;Human;human data;Human Development;human disease;Human Genetics;improved;Individual;Intellectual functioning disability;interest;Kidney;Knock-in Mouse;Knock-out;Length;Link;Location;Lysine;Messenger RNA;Modeling;Molecular;molecular phenotype;mouse development;mouse model;Mutant Strains Mice;Mutation;neuron development;Organ;Pathogenesis;Pathogenicity;Patients;Phenotype;Precision therapeutics;Protein Truncation;Proteins;response;RNA;Role;Severities;Specific qualifier value;Specificity;Symptoms;Syndrome;System;Tertiary Protein Structure;Tissues;transcriptome sequencing;Transferase;Transgenic Mice;United States;Variant;vector

PROJECT_TITLE: Dissecting out differential molecular phenotypes across Lysine(K) AcetylTransferase mutations in mouse development

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Pediatric

ORG_CITY: RICHLAND

ORG_NAME: BATTELLE PACIFIC NORTHWEST LABORATORIES

ORG_STATE: WA

PHR: Narrative The proposed research aims to develop highly specific, reproducible, and transferable multiplex targeted mass spectrometry assays to enable accurate monitoring of isoform-specific markers of endocrine and exocrine functions in type 1 diabetes (T1D) clinical research. These assays if developed successfully will make a significant contribution to more precise monitoring of pancreatic endocrine and exocrine function, the disease progression, as well as the efficacy of clinical interventions in T1D patients.

PI_NAMEs: QIAN, WEI-JUN  (contact);QU, JUN

PROGRAM_OFFICER_NAME: WANG, XUJING

PROJECT_TERMS: Affinity;Antibodies;assay development;Autoantibodies;Autoimmune;Benchmarking;Biological Assay;Blinded;Blood Glucose;C-Peptide;Child;Chromogranins;Clinical;clinical application;Clinical Chemistry;clinical efficacy;Clinical Research;cohort;Collaborations;Communities;Coupled;Detection;diabetes pathogenesis;Disease;Disease Progression;Endocrine;experience;experimental study;Failure;Fractionation;Genes;Glucagon;glycation;Goals;high throughput screening;Human;Hybrids;Immunoassay;Indiana;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;interest;Intervention;islet amyloid polypeptide;Islets of Langerhans;Laboratories;Mass Spectrum Analysis;Measures;Mediating;Medicine;Methods;Monitor;multiplex assay;nano;nanobodies;novel;Pathogenesis;Patients;Pediatric Hospitals;peptide hormone;Peptides;Performance;Philadelphia;Play;Post-Translational Protein Processing;pressure;proglucagon;prohormone;Proinsulin;Protein Isoforms;Proteins;Protocols documentation;Publications;Reagent;Reporting;Reproducibility;Research;Resolution;RNA Splicing;Role;Sampling;serological marker;Serum;Somatostatin;Specificity;Standardization;Structure of beta Cell of islet;Trypsinogen;Universities;Validation;validation studies;Variant;Work;young adult

PROJECT_TITLE: Robust Mass Spectrometric Protein/Peptide Assays for Type 1 Diabetes Clinical Applications


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: SAN ANTONIO

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: PROJECT NARRATIVE By providing access to cancer clinical trials closer to home, the Texas Pediatric NCORP MU aim at improving cancer survival for children, adolescents and young adults living in the vast catchment area comprised of Central, South and West Texas and encompassing the entire Texas-Mexico border region.

PI_NAMEs: LANGEVIN, ANNE-MARIE R. (contact)

PROGRAM_OFFICER_NAME: HECKMAN-STODDARD, BRANDY

PROJECT_TERMS: Address;Adolescent and Young Adult;Adolescent and young adult cancer patients;barrier to care;base;cancer care;cancer clinical trial;cancer survival;care delivery;Catchment Area;Certification;Child;Childhood;clinical development;Clinical Research Associate;Clinical Trials;Communities;Continuing Education;Data;Development;Diagnosis;digital media;Education;Educational Materials;Enrollment;experience;Family;Goals;health care delivery;health care disparity;Health Disparities Research;Health Services Accessibility;Home;improved;innovation;Institution;Joints;Malignant Neoplasms;meetings;Mentors;Mentorship;Mexico;Patient Education;Patients;posters;programs;Provider;recruit;Research;Research Personnel;Research Project Grants;research study;Site;Societies;South Texas;Spanish;System;Texas;Time;Training;Translating;Travel;treatment center

PROJECT_TITLE: Texas Pediatric NCORP MU


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Infectious Diseases;Malaria;Orphan Drug;Prevention;Rare Diseases;Vector-Borne Diseases

ORG_CITY: DALLAS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative. Our program seeks to identify novel inhibitors of malaria dihydroorotate dehydrogenase (DHODH) to combat the continuing threat of drug resistant malaria to clinical control of the disease. Our lead optimization program has identified potent compounds with reduced resistance risk compared to past DHODH inhibitors, and we are currently optimizing the series to identify compounds with the properties needed to support dosing in humans. We also plan to use computational and experimental approaches to identify features of enzyme/ligand interactions that can inform design of drugs with reduce resistance risk, allowing us to identify a candidate for development with the best chance to avoid clinical resistance.

PI_NAMEs: PHILLIPS, MARGARET A. (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Active Sites;Africa;African;Age;Amino Acids;Anabolism;Anti-malarials;Artemisinins;Binding;Binding Sites;Biological Assay;Calorimetry;candidate selection;Cessation of life;chemical property;Chemicals;Chemistry;Chemoprevention;Child;Clinical;clinical development;Collaborations;combat;Communicable Diseases;Complex;Computer Models;design;Development;Dihydroorotate dehydrogenase;Dihydroorotate Dehydrogenase Inhibitor;Disease;disorder control;Dose;drug candidate;Drug Design;drug discovery;Drug Kinetics;Drug resistance;Effectiveness;efficacy study;Enzyme Inhibitor Drugs;Enzymes;Flavin Mononucleotide;Free Energy;Funding;Gene Amplification;Generations;Goals;Half-Life;Hot Spot;Human;Hydrogen Bonding;improved;in silico;In Vitro;in vivo;inhibitor;Kinetics;lead optimization;Learning;Ligands;lipophilicity;Malaria;Measures;Medicine;Metabolic;Mitochondria;Modeling;Molecular Conformation;molecular dynamics;mutant;Mutation;nanomolar;next generation;novel;novel therapeutics;orotate;Outcome;Parasite resistance;Parasites;Parasitology;Pathway interactions;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phase;phase 2 study;Plasmodium;Point Mutation;Population;pre-clinical;preclinical development;pressure;programs;Property;Pyrazoles;Pyrimidine;Pyrroles;Resistance;resistance allele;Resistance development;resistance frequency;resistance mechanism;Risk;Roentgen Rays;safety study;scaffold;Series;Solubility;Source;Structure;Study models;Surface Plasmon Resonance;targeted treatment;Testing;Thermodynamics;Time;Toxic effect;Validation;Work

PROJECT_TITLE: Lead Optimization of DHODH Inhibitors for Malaria

STUDY_SECTION: DMPA

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology A Study Section [DMPA]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

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

ORG_CITY: PASADENA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PUBLIC HEALTH RELEVANCE STATEMENT (Three Sentences) There remains an important need for the development of effective and safe methods for diagnosis of breast cancer. Photoacoustic computed tomography (PACT), as the fastest growing imaging technology, is able to image breasts with rich contrast information at high spatiotemporal resolution using neither ionizing radiation nor exogenous contrast agents. In our proposed study, PACT will diagnose disease conditions in breasts with abnormal mammograms — leading to a more streamlined and accurate workup that reduces unnecessary benign breast biopsies.

PI_NAMEs: WANG, LIHONG  (contact)

PROGRAM_OFFICER_NAME: ZHANG, YANTIAN

PROJECT_TERMS: 3-Dimensional;Acoustics;attenuation;Benign;Biopsy;Blood Vessels;Breast;Breast biopsy;breast cancer diagnosis;breast imaging;breast lesion;Clinical;clinically significant;Contrast Media;cost;detection limit;Development;Diagnosis;diagnostic tool;diffuse optical tomography;disease diagnosis;Elasticity;elastography;follow-up;Hemoglobin;Hemorrhage;Image;imager;imaging system;Imaging technology;in vivo;innovation;Ionizing radiation;Lasers;Lead;Lesion;Light;Malignant - descriptor;Mammary Gland Parenchyma;Mammographic screening;Mammography;Methods;Modeling;Morphologic artifacts;Motion;Operative Surgical Procedures;Optics;Oxygen;Pain;Pathology;Patients;Penetration;public health relevance;Resolution;response;Roentgen Rays;Scanning;screening;Shapes;side effect;soft tissue;spatiotemporal;Speed;Stress;System;Systemic Therapy;temporal measurement;Testing;Tissues;tomosynthesis;Tumor Volume;Ultrasonography;ultrasound;X-Ray Computed Tomography

PROJECT_TITLE: High-speed panoramic 3D photoacoustic computed tomography of the breast


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology

PHR: Project Narrative Tissue structure and function requires coordination between the dynamic physical organization of cells and the genetic programs controlling cell phenotype. Our understanding of this coordination is poor due to limitations of existing experimental systems, but critically needed to understand development and combat pathologies such as cancer and cardiovascular disease. This proposal is designed to contribute new molecular and platform technologies that will uncover fundamental molecular control systems at cell-cell interfaces that orchestrate these physical and genetic processes.

PI_NAMEs: KUTYS, MATTHEW L (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: 3-Dimensional;Actins;Adhesions;Adhesives;Architecture;Area;arm;Behavior;Biological Process;Biomimetics;Biophysics;Cardiovascular Diseases;cell behavior;Cell Communication;cell cortex;Cell-Cell Adhesion;Cells;combat;Complex;Crowding;design;Development;Disease;Endothelial Cells;Engineering;Epithelium;Exposure to;Extracellular Matrix;Family;Gene Expression;gene regulatory network;Genetic;Genetic Processes;Genetic Transcription;Goals;human model;human tissue;In Vitro;in vivo;insight;Instruction;interdisciplinary approach;Investigation;Laboratories;Malignant Neoplasms;Mechanics;Methods;Microfluidics;Microscopy;Molecular;Natural regeneration;next generation;notch protein;operation;Output;Pathology;Pathway interactions;Phenotype;physical process;Postdoctoral Fellow;Process;programs;Proteomics;receptor;Research;shear stress;Signal Transduction;Structure;System;Technology;technology platform;Time;Tissues;tool

PROJECT_TITLE: Decoding cortical Notch signaling and morphogenic instruction at cell-cell interfaces

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biodefense and Related Countermeasures;Brain Disorders;Dementia;Emerging Infectious Diseases;Infectious Diseases;Neurodegenerative;Neurosciences;Rare Diseases;Transmissible Spongiform Encephalopathy (TSE)

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE  Prion diseases are fatal neurodegenerative disorders caused by the misfolding of the cellular prion protein into aggregates that target specific cell types and brain regions. Heparan sulfate (HS) proteoglycans promote the selective internalization and replication of conformationally variable prions (prion strains) in different neural cell types. These studies will help to define the molecular mechanisms of selective cell vulnerability in neurodegenerative diseases and may provide new therapeutic targets based on blocking HS:prion binding.

PI_NAMEs: AGUILAR CALVO, PATRICIA  (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Abeta clearance;abeta oligomer;Affect;Age;age related changes;age related neurodegeneration;aged;Alzheimer's Disease;Alzheimer's disease brain;Amyloid beta-Protein;Animal Model;Astrocytes;Binding;Brain;Brain region;Cause of Death;Cell membrane;Cell surface;cell type;Cells;Cerebellum;Chemicals;Dependence;design;differential expression;Disease;disease phenotype;Engineering;Environment;Extracellular Matrix;Glycocalyx;Glycoproteins;Goals;Heparan Sulfate Proteoglycan;Heparin;Heparitin Sulfate;Hippocampus;IGF Type 2 Receptor;In Vitro;in vivo;innovation;Length;Lesion;Lysosomes;Malignant Neoplasms;mannose 6 phosphate;Mass Spectrum Analysis;mast cell;Measures;Mediating;Mentors;Microglia;mimetics;misfolded protein;Molecular;Molecular Conformation;mouse model;Mus;Nerve Degeneration;neuroblastoma cell;Neurodegenerative Disorders;Neurons;neuroprotection;new therapeutic target;Oligodendroglia;Pathogenesis;Pathway interactions;Patients;Pattern;Persons;Physiological;Pilot Projects;polysulfated glycosaminoglycan;Population;Post-Translational Protein Processing;prevent;Prion Diseases;Prions;protein aggregation;Protein Isoforms;Proteins;PrP;rational design;Research;Role;Senile Plaques;Sulfate;Tail;Techniques;Testing;therapeutic target;Training;transmission process;Tropism;uptake;Variant

PROJECT_TITLE: Role of heparan sulfate in neural cell vulnerability to prions


NIH_SPENDING_CATS: Aging;Biomedical Imaging;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dietary Supplements;Microbiome;Nutrition;Osteoporosis;Prevention;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: HEBREW REHABILITATION CENTER FOR AGED

ORG_STATE: MA

PHR: PROJECT NARRATIVE and Relevance to Public Health Our proposed study is an 18-month randomized, double-blinded, placebo-controlled clinical trial in 220 postmenopausal women aged 60 years and above. Our objective is to test the efficacy of a probiotic/prebiotic combination (“synbiotic”) on the skeleton in a clinical trial that is designed to provide mechanistic insights into the action of the symbiotic supplement. Understanding these mechanisms might lead to the development of medical food supplements to aid in the dietary management of aging associated bone loss. 1

PI_NAMEs: SAHNI, SHIVANI  (contact)

PROJECT_TERMS: Adult;Age;Age-Related Bone Loss;aged;Aging;aging related;American;Biochemical Markers;Biomechanics;bone;Bone Density;bone loss;bone mass;bone strength;bone turnover;Clinical;Clinical Research;Clinical Trials;Colon;comparison control;Compressive Strength;Consumption;Controlled Clinical Trials;cost;Data;design;Development;Diet;dietary;Dietary Fiber;Dietary Intervention;Double-Blind Method;Drug Prescriptions;Dual-Energy X-Ray Absorptiometry;efficacy testing;Enzymes;Equilibrium;Feces;Fermentation;Fiber;Food;Food Supplements;Fracture;fracture risk;fruits and vegetables;Genes;Goals;Guidelines;gut microbes;gut microbiome;Health Promotion;Homologous Gene;Hydrolase;improved;Inflammation;inflammatory marker;insight;Intake;Interleukins;Maintenance;Measures;Mediating;medical food;Metabolism;metagenome;metatranscriptome;Microbe;microbial;middle age;Minerals;mouse model;Mus;novel;older adult;older women;Osteitis;osteoclastogenesis;Osteopenia;Osteoporosis;Ovariectomy;Pathway interactions;Peripheral;Placebo Control;Placebos;Plants;Postmenopause;prebiotics;preclinical study;primary outcome;Probiotics;Production;Public Health;Randomized;Recommendation;Regulatory T-Lymphocyte;secondary outcome;Shotgun Sequencing;side effect;skeletal;Skeleton;spine bone structure;Testing;TNF gene;Vertebral column;Vitamin K 2;Vitamins;Volatile Fatty Acids;Weight-Bearing state;Woman;women's treatment;X-Ray Computed Tomography

PROJECT_TITLE: A randomized, double-blind, placebo-controlled, clinical trial of a probiotic/prebiotic supplement for the dietary management of age-related bone loss.

STUDY_SECTION: AIMR

STUDY_SECTION_NAME:
Aging, Injury, Musculoskeletal, and Rheumatologic Disorders Study
Section[AIMR]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Obesity;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROPOSAL NARRATIVE Cardiometabolic disease risk is emerging earlier in life than ever before and disproportionately affects racial and ethnic minority populations. This proposal will apply advanced methods in epidemiology and implementation science to identify, adapt, and test a multi-component intervention to address cardiometabolic disease risk in Samoan children. Results will inform action that can be taken at the earliest possible opportunity to mitigate cardiometabolic disease risk and reduce health disparities among Samoans and other Pacific Islander populations.

PI_NAMEs: CHOY, COURTNEY CHEU LIN (contact)

PROGRAM_OFFICER_NAME: MINTZER, KEITH A

PROJECT_TERMS: 11 year old;13 year old;4 year old;8 year old;Active Learning;Address;Affect;Age;Americas;Area;Award;Behavioral;Belief;beneficiary;Blood Pressure;blood pressure elevation;Body fat;Body mass index;boys;Cardiometabolic Disease;cardiometabolic risk;career development;Child;Child Health;Clinical Trials;cohort;Cohort Studies;combat;Communities;cost;Country;Data;Development;diabetic;Disease Marker;disorder risk;Early Intervention;Effectiveness;efficacious intervention;Enrollment;Ensure;Environment;Environmental Risk Factor;Epidemiology;ethnic minority population;Evaluation;evidence base;experience;Faculty;Focus Groups;girls;Glycosylated Hemoglobin;Glycosylated hemoglobin A;Goals;Growth;Health;health assessment;High Prevalence;high risk;Human Biology;implementation framework;implementation science;Income;indexing;Infrastructure;innovation;Intervention;Interview;leadership development;learning strategy;Life;Life Style;Longitudinal Studies;member;Mentors;Mentorship;Methods;Modeling;modifiable risk;multi-component intervention;multidisciplinary;Obesity;Outcome;Overweight;Pacific Islander;Pacific Islands;Personal Satisfaction;Phase;pilot test;Polynesian;Population;Populations at Risk;Positioning Attribute;Prediabetes syndrome;Prevalence;Prevention;primary caregiver;Probability;programs;Public Health;Qualitative Methods;Qualitative Research;racial minority population;Reduce health disparities;Research;Research Training;Resource-limited setting;Risk;Risk Factors;Samoa;Samoan;scale up;Scientist;skills;Southeastern Asia;tenure track;Testing;therapy development;Training;Underserved Population;United States;usability;Work

PROJECT_TITLE: Developing a multi-component intervention to address cardiometabolic disease (CMD) risk in Samoan children

STUDY_SECTION: MTI

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


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Complementary and Integrative Health;Drug Abuse (NIDA only);HIV/AIDS;Infectious Diseases;Natural Products;Substance Misuse

ORG_CITY: Auburn

ORG_DEPT: PHARMACOLOGY

ORG_NAME: AUBURN UNIVERSITY AT AUBURN

PHR: Project Narrative Individuals living with the stress of HIV are at increased risk of substance abuse, including abuse of natural substances, such as the botanical, Mitragyna speciosa (kratom). This investigation will address the critical safety issue of botanical-HIV drug interactions as natural substances can alter therapeutic drug levels in the blood and thereby affect the safety and efficacy of HIV drugs. By enabling the fundamental understanding of interactions between HIV drugs and kratom, this project will provide a rationale for confirmatory clinical trials and ultimately, an improved efficacy of HIV treatment protocols.

PI_NAMEs: CALDERON, ANGELA ISABEL (contact)

PROGRAM_OFFICER_NAME: ANANTHAN, SUBRAMANIAM

PROJECT_TERMS: Acceleration;Adverse event;Affect;Alcohol abuse;alcohol risk;Alkaloids;Analytical Chemistry;antiretroviral therapy;Applications Grants;Area;Binding;Binding Proteins;Biological Assay;Blood;Botanicals;Cells;Cessation of life;Clinical;Clinical Research;clinically relevant;confirmatory clinical trial;Core Facility;CYP2D6 gene;CYP3A4 gene;Cytochrome P450;Data;Databases;Dialysis procedure;dosage;Dose;Drug Interactions;Drug Kinetics;drug metabolism;Drug usage;Education;emtricitabine;Ensure;Enzymes;Equilibrium;follow-up;Foundations;Funding;Future;Glucuronosyltransferase;Goals;Hepatic;Hepatocyte;HepG2;HIV;HIV anti-retroviral;HIV/AIDS;Human;improved;In Vitro;in vitro Model;Incubated;Individual;innovation;insight;Institution;instrumentation;Investigation;Knowledge;Leadership;Legal;Link;Liver Microsomes;Measures;Mediating;Metabolism;Mitragyna;mRNA Expression;National Institute of Drug Abuse;Natural Products;Natural Substance;Opioid;Oregon;Outcome Study;Patients;Persons;Pharmaceutical Preparations;Pharmacognosy;pharmacokinetic model;Pharmacology;Pharmacy facility;Phase;Physiological;Plant Leaves;Plasma;Plasma Proteins;Positioning Attribute;preclinical study;Preparation;Property;Quantitative Evaluations;quetiapine;Recombinants;Recommendation;Regimen;Reporting;Research;Rifampin;Risk;Safety;Serotonin Syndrome;Serum;Serum Albumin;Serum Proteins;Standardization;Stimulant;Stress;Substance abuse problem;substance use;System;Tenofovir;Testing;Therapeutic;therapy outcome;Toxic effect;Treatment Efficacy;Treatment Protocols;Treatment-related toxicity;United States Food and Drug Administration;United States National Institutes of Health;Universities;venlafaxine

PROJECT_TITLE: In vitro assessment of kratom pharmacokinetic CYP interactions with HIV ART drug metabolism

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Gene Therapy;Genetics;Human Genome;Immunotherapy

ORG_CITY: AUGUSTA

ORG_NAME: AUGUSTA UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative The STAT5 signaling pathway is critical for T cell expansion, persistence, and function. The proposed research will characterize the transcriptomic and epigenetic features of antitumor CD4 T cells expressing a constitutively active form of STAT5 and establish the therapeutic utility of these genetically modified CD4 T cells in the context of adoptive T-cell therapy including the use of T cells expressing chimeric antigen receptors (CAR).

PI_NAMEs: SHI, HUIDONG ;ZHOU, GANG  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: anti-tumor immune response;Antigens;antitumor effect;ATAC-seq;Bioinformatics;Biological Models;cancer immunotherapy;Cancer Patient;CAR T cell therapy;CD19 gene;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Characteristics;chimeric antigen receptor;ChIP-seq;clinical application;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;cytokine;Data;Dendritic cell activation;Ectopic Expression;effective therapy;effector T cell;Endowment;Epigenetic Process;epigenetic profiling;epigenomics;Epitope spreading;Event;exhaust;exhaustion;Exposure to;Functional disorder;Gene Expression;Gene Expression Profile;Gene Modified;gene-editing approach;Genetic Transcription;genome-wide;Growth;Heterogeneity;histone modification;Histones;Human;IL7 gene;Immunologics;Immunotherapy;improved;In Vitro;Infiltration;Inflammatory;Infusion procedures;Knock-out;Laboratories;Lymphoma;Maintenance;Malignant Neoplasms;Mediating;Modeling;Mus;novel strategies;overexpression;Patient-Focused Outcomes;Patients;Phenotype;Population;pre-clinical;Pre-Clinical Model;Predisposition;prevent;Process;Production;Productivity;progenitor;Relapse;Reporting;Research;Resistance;Role;Signal Induction;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;STAT protein;Stat5 protein;System;Systems Biology;T cell therapy;T-Cell Activation;T-Lymphocyte;Technology;Therapeutic;therapy outcome;transcriptomic profiling;transcriptomics;Treatment Efficacy;tumor;tumor growth;Tumor Immunity;tumor microenvironment;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Persistent STAT5 signaling in polyfunctional CD4 T cells and its application in adoptive T cell therapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: EAST LANSING

ORG_DEPT: PHYSIOLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: Mast cells (MCs) are innate immune cells that play a central role in sickness, allergies, and psychiatric diseases, yet the genetic and transcriptional mechanisms by which MCs are regulated remain poorly understood, and the means to target MCs to treat infection and stress-related diseases remain largely unavailable. We have uncovered a novel transcription factor in MC activation and modulation, ΔFosB, and our preliminary evidence suggests that its expression in MCs is essential for normal physiology and behavioral responses to immune challenge or chronic stress in mice. The proposed work will uncover the specific mechanisms by which ΔFosB regulates MC function in vivo as well as the key transcriptional targets of ΔFosB in MCs that may act as molecular handles for therapeutic intervention in MC-related diseases or infection.

PI_NAMEs: MOESER, ADAM ;ROBISON, ALFRED J (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: Ablation;Acute;Adult;Affect;Allergic Reaction;Anxiety;anxiety reduction;Behavior;Behavioral;behavioral response;biochemical tools;Blood Vessels;Bone Marrow;Brain;Cell Degranulation;Cell Physiology;Cell Proliferation;Cells;Chronic;Chronic stress;Cleavage Under Targets and Release Using Nuclease;Cultured Cells;cytokine;Data;Development;Disease;Enzymes;Etiology;Exhibits;Exposure to;Family;Feedback;FOSB gene;Future;Gene Expression;gene function;Gene Targeting;Genes;Genetic;Genetic Transcription;Histamine;Hypersensitivity;Image;Imaging Techniques;Immune;immune activation;immune function;Immune System Diseases;Immunohistochemistry;In Vitro;in vivo;Infection;Inflammation;innovation;Link;Lipopolysaccharides;Location;lymphatic vessel;mast cell;Mediating;Mediator;Membrane;Meningeal;Meninges;Mental Depression;Mental disorders;Molecular;Mood Disorders;Moods;Mus;Neurodegenerative Disorders;Neuroimmune;neuroinflammation;Neurons;neuropsychiatric disorder;novel;Peptide Hydrolases;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physiological;Physiology;Play;Positioning Attribute;prevent;Regulation;response;Role;Serotonin;sex;Stimulus;Stress;Techniques;Testing;Therapeutic Intervention;Tissues;tool;Toxin;transcription factor;Transcription Factor AP-1;transcriptome sequencing;two-photon;Work

PROJECT_TITLE: Transcriptional mechanisms in mast cells underlying immune function and disease


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Tickborne Diseases;Vector-Borne Diseases

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative Type VI Secretion Systems (T6SS) are macromolecular nanomachines and important virulence determinants present in one-quarter of Gram-negative bacteria, including many that cause serious human diseases, and thus, they are an important new target for strategies to combat infections caused by the bacterial pathogens that use them. However, to develop these strategies, we must better understand the composition, structure, and function of the T6SS. This proposal seeks to fill the gaps in our understanding of the T6SS in Francisella, which is classified as a Tier 1 Select Agent and requires the T6SS for its extremely high infectivity and pathogenicity.

PI_NAMEs: HORWITZ, MARCUS AARON (contact);ZHOU, Z HONG

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, SUMAN

PROJECT_TERMS: Aerosols;Affinity;Animals;Attenuated Vaccines;Bacteria;Bacterial Infections;Biochemical;Bioterrorism;Burkholderia pseudomallei;Cells;Chemicals;Classification;combat;Complex;Contracts;crosslink;Cryo-electron tomography;Cryoelectron Microscopy;Cues;Cytosol;design;Development;Disease;Dose;Early identification;Electrons;Endowment;Escherichia coli;Eukaryotic Cell;Exhibits;Federal Government;Foundations;Francisella;Francisella tularensis;Free Energy;Freezing;Future;Genes;Genetic;genetic manipulation;Goals;Gram-Negative Bacteria;Homologous Gene;Human;human disease;human pathogen;Hybrids;In Situ;Infection;Infection prevention;Injections;Knowledge;Label;Life Style;Macrophage;Mass Spectrum Analysis;Mediating;Membrane;Methods;Modeling;Molecular Conformation;Molecular Structure;Morbidity - disease rate;mortality;Mutagenesis;nanomachine;particle;Pathogenesis;pathogenic bacteria;Pathogenicity;Pathogenicity Island;Phagosomes;prevent;Process;Prokaryotic Cells;protein complex;Proteins;Proteomics;reconstruction;Rest;Role;Rotation;Sequence Homology;Structure;System;Technology;Testing;Toxin;Tube;Tularemia;Vibrio cholerae;Virulence;Virulent;Western Blotting

PROJECT_TITLE: Composition, Atomic Structure and Function of the Francisella Type 6 Secretion System, a Distinct Subtype Essential for Phagosomal Escape, Intracellular Replication, and Virulence

STUDY_SECTION: PCMB

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


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative Antibiotics represent a landmark achievement of medical science and have saved countless lives. Unfortunately, their efficacy is rapidly declining due to the emergence of drug-resistant pathogens. This study combines mathematical tools from physics with quantitative experiments on pathogenic bacteria to investigate how the spatial arrangement of bacteria in microbial communities contributes to—and is shaped by—the spread of resistance to widely-used antibiotics.

PI_NAMEs: WOOD, KEVIN  (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Achievement;Antibiotic Resistance;Antibiotics;Architecture;Bacteria;bacterial community;Bacterial Infections;Behavior;Biological Models;Biology;Cancer Biology;cell community;Cells;Communities;Complex;Disease;drug discovery;drug resistant pathogen;Ecology;Environment;Evolution;Experimental Models;experimental study;Health;Innovative Therapy;Length;Mathematics;Medical;microbial;Microbial Biofilms;microbial community;Molecular;pathogenic bacteria;Pharmaceutical Preparations;Physics;Population;programs;Public Health;Research;Resistance;response;Role;Science;Shapes;Spatial Behavior;spatiotemporal;Structure;Testing;theories;tool;Work

PROJECT_TITLE: Spatiotemporal Dynamics of Collective Antibiotic Resistance in Microbial Communities

STUDY_SECTION: MRAA

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


ORG_CITY: IRVINE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Glioblastoma multiforme (GBM) is the most common and deadliest form of brain cancer. The proposed program seeks to evaluate FLASH, a new radiation delivery platform that has shown strong promise for targeting cancer cells with significantly less harm to surrounding healthy tissue than is possible with current radiotherapies. Findings from proposed studies will enable the rapid translation of FLASH to the clinic, and provide a long-awaited breakthrough in the treatment of GBM.

PI_NAMEs: LIMOLI, CHARLES  (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Aftercare;Animals;Autopsy;behavior test;Brain;Brain Neoplasms;cancer cell;cancer type;Canis familiaris;Cause of Death;Characteristics;Chemicals;Clinic;Clinical;clinical implementation;Clinical Management;clinical practice;Cognition;Combined Modality Therapy;Conduct Clinical Trials;conventional dosing;Data;design;Dose;Dose Limiting;Dose Rate;dosimetry;Electron Beam;Electrons;Evaluation;follow-up;Follow-Up Studies;functional outcomes;genetic approach;Glioblastoma;Glioma;glutathione peroxidase;Goals;high risk;Histologic;Human;Hydrogen Peroxide;Hypoxia;Immunologics;Impaired cognition;improved;Indiana;Inflammation;innovation;Investigation;Ions;Irradiated tumor;irradiation;Lipid Peroxidation;Malignant neoplasm of brain;Malignant Neoplasms;metal chelator;Metals;Metastatic malignant neoplasm to brain;Modality;Modeling;Molecular;mouse model;Nature;neurobehavioral;neurobiological mechanism;Neurocognition;Neurocognitive;neurocognitive test;neuroinflammation;Neurons;Normal tissue morphology;novel;operation;Organ;Oxidation-Reduction;oxidative damage;Oxygen;oxygen toxicity;Pathology;Patients;performance site;pharmacologic;Physics;Physiological;preclinical study;programs;Protocols documentation;Radiation;radiation delivery;Radiation Dose Unit;Radiation Oncology;Radiation Protection;Radiation therapy;Radiation-Induced Change;Radiobiology;Radiometry;recruit;Research;Research Personnel;response;Rodent;Roentgen Rays;Role;Safety;Series;standard care;Standardization;Structure;Switzerland;technological innovation;temozolomide;Testing;Therapeutic;Therapeutic Index;Time;Tissues;Toxic effect;Transgenic Mice;Translating;Translations;treatment optimization;Treatment Protocols;tumor;tumor progression;Tumor Tissue;Universities;virtual;Work

PROJECT_TITLE: Increasing the therapeutic index of brain tumor treatment through innovative FLASH radiotherapy


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases

PHR: PROJECT NARRATIVE – Project 1: Optimizing Treatment of GBM by FLASH The suboptimal therapeutic index of brain tumor therapies, including radiotherapy, is in great need of improvement. The proposed program seeks to evaluate ultra-rapid FLASH radiotherapy, a new radiation treatment approach that has shown strong promise for killing cancer cells with significantly less harm to surrounding healthy brain tissue than is possible with current technologies. In this project, we will compare FLASH and conventional dose rate irradiation in clinically relevant regimens and evaluate mechanistic endpoints to accelerate clinical translation of this novel paradigm.

PROJECT_TERMS: Acceleration;Address;Aftercare;Anatomy;Behavioral;Biology;Blood Vessels;Brain;Brain Injuries;Brain Neoplasms;brain tissue;cancer cell;cancer therapy;Canis familiaris;Cause of Death;Cessation of life;chemotherapy;Clinic;Clinical;Clinical Management;clinical practice;clinical translation;Clinical Trials;clinically relevant;Cognition;Cognitive;cognitive function;Collaborations;comparison control;Complement;Complex;conventional dosing;Coupled;Cranial Irradiation;Data;Data Set;design;Development;Dose;Dose Rate;dosimetry;Electron Beam;Electrons;experimental study;Fractionation;Glioblastoma;Goals;Human Resources;Immunologics;immunoregulation;improved;indexing;Indiana;Individual;Inflammation;Inflammatory;inflammatory marker;Infrastructure;innovation;insight;Institution;International;irradiation;Laboratories;Medical;Modality;Modeling;Molecular;mouse model;multidisciplinary;Mus;neurobehavioral;neurobiological mechanism;Neurocognition;Neurocognitive;Neurologic;Neurons;neurotoxicity;Normal tissue morphology;novel;novel strategies;Oncologist;Outcome;Outcome Assessment;Oxidation-Reduction;Oxygen;Patients;Physics;pre-clinical;preclinical imaging;preclinical study;Program Research Project Grants;programs;Radiation;Radiation Injuries;Radiation Oncology;Radiation therapy;Radiation-Induced Change;Radiobiology;Radiotherapy Research;Regimen;Research;Research Design;response;Roentgen Rays;Science;Series;Structure;success;Symptoms;Techniques;Technology;temozolomide;Testing;Therapeutic Index;therapy design;Time;Toxic effect;Translating;Translations;treatment optimization;tumor;tumor progression;Tumor Tissue;Universities;University Hospitals;Vascular Morphologic Change;Work


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: CHEMISTRY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Project Narrative The picornavirus 3CD protein is central to every stage of the virus life cycle, including in genome replication and encapsidation, and in the formation of virus-induced replication organelles. Our proposal seeks to elucidate structural states sampled by 3CD that are responsible for its many functions and which differentiate its functions from those of the related 3C and 3D proteins. Characterization of these various structural states will provide a framework for devising more effective anti-viral strategies against a range of current and emerging human virus pathogens, including rhinovirus, enterovirus, coronavirus and poliovirus.

PI_NAMEs: BOEHR, DAVID DOUGLAS (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: 1-Phosphatidylinositol 4-Kinase;3-Dimensional;Active Sites;Affinity;Amino Acid Substitution;Anti-viral Agents;attenuation;Behavior;Binding;Binding Proteins;Biogenesis;Biological Assay;Biological Models;Biological Process;Biophysics;Capsid Proteins;Cells;Complement;Coronavirus;Development;Drug Targeting;Elements;emerging pathogen;Enterovirus;Enterovirus 68;Enterovirus 71;Environment;Enzymes;Event;Family Picornaviridae;flexibility;Funding;Genome;Grant;Heart;Human;Human poliovirus;Immune response;inhibitor;insight;Life Cycle Stages;Lipid Binding;Lipids;Membrane;Membrane Proteins;Molecular Conformation;Motion;Mutagenesis;nanosecond;NMR Spectroscopy;novel;Nucleotides;Organelles;pathogenic virus;Peptide Hydrolases;Peptides;Phosphatidylinositols;phosphodiester;Play;Polymerase;Polyproteins;Process;Production;Proliferating;Protein Conformation;protein function;Proteins;Proteolysis;Proteolytic Processing;Proteome;Replication-Associated Process;Rhinovirus;Ribonucleotides;RNA;RNA Binding;RNA replication;RNA Viruses;RNA-Directed RNA Polymerase;Roentgen Rays;Role;Sampling;Specificity;Structure;Surface;System;Thermodynamics;Translation Process;vaccine development;Viral;Viral Proteins;viral RNA;Virus;Virus Diseases;Virus Inhibitors;Virus Replication;Work

PROJECT_TITLE: Watching conformational rearrangements in picornavirus replication proteins

STUDY_SECTION: MSFC

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


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE/PUBLIC HEALTH RELEVANCE Identifying solutions for HIV-1 and emerging global requires combined expertise and collaboration among scientists. A new generation of scientists is needed who are trained across disciplines to enable real world solutions to complex problems. Efficiency and innovation in the detection, tracking, treatment and prevention of HIV-1 and other infectious diseases is made possible by investing in training young investigators to become facile in thinking and working across multiple disciplines to solve complex problems.

PI_NAMEs: FERRARI, GUIDO ;THIELMAN, NATHAN M (contact)

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Interdisciplinary Study;Training Programs

PROJECT_TITLE: Interdisciplinary Research Training Program in AIDS

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases

PHR: PROJECT NARRATIVE – PROJECT 2 Radiotherapy remains a frontline treatment for primary and metastatic brain cancers, like Glioblastoma multiforme (GBM), but can result in debilitating cognitive side effects. The proposed program seeks to evaluate FLASH, a new radiation delivery platform that has shown strong promise for eradicating cancer cells with significantly less harm to surrounding healthy tissue than is possible with current radiotherapies. This project involves a series of long-term neurocognitive studies that will provide insight into the mechanisms of how normal tissue damage is spared by FLASH.

PROJECT_TERMS: Acute;Aftercare;Animals;behavior test;Behavioral;behavioral outcome;Blood Vessels;Brain;Brain Neoplasms;cancer cell;cancer therapy;Canis familiaris;Chronic;Clinic;Clinical;clinical practice;Clinical Trials;clinically relevant;Cognition;Cognitive;cognitive function;comparison control;conventional dosing;Coupled;Data;Data Set;Development;Disease;Dose;Dose Limiting;Dose Rate;dosimetry;Electron Beam;Exhibits;Foundations;Glioblastoma;Goals;Immunologics;immunoregulation;Impaired cognition;improved;indexing;Inflammation;Inflammatory;innovation;insight;irradiation;Knowledge;Malignant neoplasm of brain;Malignant Neoplasms;Measures;Medical;Modality;Molecular;Morphology;mouse model;Mus;neurobehavioral;neurobiological mechanism;Neurocognitive;neuroinflammation;Neurons;neurotransmission;Normal tissue morphology;novel;Oncologist;Outcome;Oxidation-Reduction;Oxygen;Patients;Pediatric cohort;Physics;pre-clinical;preclinical study;Prognosis;programs;Quality of life;Radiation;radiation delivery;Radiation Injuries;Radiation therapy;Radiation-Induced Change;Research;Research Design;Series;side effect;single fraction radiation;Structure;Survivors;Technology;temozolomide;Testing;Therapeutic;Therapeutic Index;tissue injury;Tissues;Toxic effect;Translating;translational impact;Translations;treatment arm;tumor;weapons

PROJECT_TITLE: Project 2: Sparing in Tumor Free Animals


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Depression;Machine Learning and Artificial Intelligence;Major Depressive Disorder;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Neurosciences;Precision Medicine;Serious Mental Illness

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project narrative In the proposed project, we focus on neuroanatomy and neurofunctional connectivity in MDD. We aim to identify imaging signatures and subtypes in MDD by applying state-of-the-art harmonization, pattern analysis and machine learning methods to structural MRI and resting state functional MRI. The analytic methods allow us to quantify the neuroanatomical and neurofunctional connectivity patterns that comprise MDD to provide powerful predictive markers at the individual level. Our goal is to arrive at a new neuroanatomical-neurofunctional (NA-NF) dimensional coordinate system in MDD (COORDINATES MDD), whereby each dimension reflects a different pattern of brain alterations, hence capturing the underlying NA-NF heterogeneity in quantifiable, replicable and neurobiologically-based metrics.

PI_NAMEs: DAVATZIKOS, CHRISTOS  (contact);FU, CYNTHIA

PROGRAM_OFFICER_NAME: FERRANTE, MICHELE

PROJECT_TERMS: Adult;analytical method;Anatomy;Big Data;Biological Markers;biomarker development;Brain;Brain region;Clinical;Clinical Data;clinical heterogeneity;clinical phenotype;Clinical Trials;cohort;Collaborations;Communities;complex data;Controlled Clinical Trials;Data;Data Set;deep learning;depressive symptoms;Development;Diffusion Magnetic Resonance Imaging;Dimensions;Disabling;Disease;Electroencephalography;Ensure;Etiology;Formulation;Functional Magnetic Resonance Imaging;Goals;Heterogeneity;Image;Image Analysis;imaging modality;Individual;individual patient;International;Knowledge;Knowledge Discovery;Machine Learning;machine learning method;Magnetic Resonance Imaging;Major Depressive Disorder;Measurement;Measures;Methodology;Methods;Modality;Modernization;Multimodal Imaging;multimodality;neural;Neuroanatomy;Neurobiology;neuroimaging;neuropsychiatric disorder;neuropsychiatry;Outcome;Participant;Pathology;Patients;Pattern;personalized biomarkers;personalized diagnostics;Pharmaceutical Preparations;Phenotype;phenotypic data;Placebo Control;Positioning Attribute;predict clinical outcome;Prediction of Response to Therapy;predictive marker;predictive modeling;Probability;prognostication;prospective;Recurrence;Research;Resistance;Resources;Rest;Risk;Sampling;Selection for Treatments;Site;Statistical Models;Stratification;structural imaging;Structure;supervised learning;Symptoms;System;Testing;Time;Treatment outcome;treatment response;Work

PROJECT_TITLE: Disentangling the anatomical, functional and clinical heterogeneity of major depression, using machine learning methods

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


PHR: Project Narrative - Project 4: Mechanistic Basics of FLASH Effect: Role of O2 Recently, exciting and unexpected new data in several animal models strongly supports the premise that ultra- high dose rate irradiation termed FLASH radiotherapy (FLASH-RT) can result in significant sparing of normal tissue while preserving tumor responses, effectively leading to significant increases in the therapeutic window for improving radiotherapy outcomes in brain cancer. However, the mechanisms for this effect are currently unknown. Project 4 will build on the exciting preliminary data to determine how reactions of O2 with free radicals formed at the time of FLASH-RT may be the drivers of the remarkable differential responses of normal and cancer tissue to FLASH-RT.

PROJECT_TERMS: Adjuvant;Animal Model;animal tissue;Animals;ascorbate;Biochemical;Biological;Biological Markers;biomarker validation;Blood;Brain Neoplasms;brain tissue;Breathing;cancer cell;Cancer Survivor;cancer therapy;Carbogen;Carbon Dioxide;Cell Respiration;Cellular Metabolic Process;chemoradiation;Clinical;Clinical Trials;conventional dosing;cost;Data;Development;Dose;Dose Rate;Electrons;Exposure to;Ferritin;Free Radicals;functional outcomes;genetic approach;genetic manipulation;glutathione peroxidase;Hydrogen Peroxide;improved;Inflammatory Response;innovation;Ions;iron metabolism;irradiation;Lead;Learning;Lipid Peroxidation;Malignant neoplasm of brain;Malignant Neoplasms;Measurement;Mediating;Metabolism;metal chelator;Metals;Modeling;Morbidity - disease rate;Morphology;mortality;mouse model;Neurocognitive;Neurons;Normal Cell;Normal tissue morphology;Outcome;overexpression;Oxidation-Reduction;Oxidative Stress;Oxygen;pharmacologic;Photons;preservation;Radiation;Radiation Physics;Radiation therapy;Radiochemistry;Reaction;response;Role;Stress Tests;Testing;Therapeutic;Therapeutic Index;therapy outcome;Time;tissue injury;Tissues;Treatment Efficacy;treatment response;tumor;Tumor Tissue


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_CITY: BERKELEY

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE Although the glucocorticoid receptor has been shown to directly increase the expression of genes encoding gluconeogenic enzymes to promote hepatic gluconeogenesis, here we identify sphingosine-1-phosphate signaling as a unique pathway that is induced upon chronic glucocorticoid exposure, which can occur upon prolonged stress or glucocorticoid therapy. We will dissect the mechanisms governing sphingosine-1- phosphate signaling mediated enhancement of glucocorticoid induced hepatic gluconeogenesis. The knowledge gained from this proposed study will provide novel insights into therapeutic interventions against steroid induced hyperglycemia.

PI_NAMEs: WANG, JEN-CHYWAN  (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Affect;Agonist;antagonist;Attenuated;Binding;Biological Assay;blood glucose regulation;Cells;Cholesterol;cholesterol biosynthesis;chromatin immunoprecipitation;Chronic;comorbidity;Disease;Enzymes;Exposure to;extracellular;Extracellular Space;Functional disorder;Gene Expression;Gene Expression Profiling;Genes;Genetic Transcription;genome-wide;Glucocorticoid Receptor;glucocorticoid-induced orphan receptor;Glucocorticoids;Gluconeogenesis;Gluconeogenesis Induction;Gluconeogenesis Inhibition;Glucose;Hepatic;hepatic gluconeogenesis;Hepatocyte;hepatoma cell;Hyperglycemia;Immune System Diseases;improved;in vivo;Inflammatory;inhibitor;insight;knock-down;Knockout Mice;Knowledge;Liver;MAPK1 gene;MAPK3 gene;Mediating;Membrane;Metabolic Diseases;Metabolism;Modeling;Mus;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;Orphan;overexpression;Pathway interactions;Patients;Pharmacotherapy;Physiological;Production;Pyruvate;Rattus;receptor;receptor expression;recruit;Regulation;response;Response Elements;Role;Signal Transduction;Signaling Molecule;Sphingosine;sphingosine 1-phosphate;sphingosine kinase;Sphingosine-1-Phosphate Receptor;SPHK1 enzyme;Steroids;Stress;Surface;Testing;Therapeutic Intervention;transcriptome

PROJECT_TITLE: Sphingosine-1-phosphate Signaling and the Chronic Glucocorticoid Exposure Induced Glucose Homeostasis Disorder

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


PROJECT_TERMS: Accounting;Animals;Back;Biology;Biometry;Blinded;Brain;Brain Neoplasms;Budgets;Calibration;Caring;Clinical;clinical implementation;Clinical Sciences;Collection;Communication;Communities;Consultations;conventional dosing;Data;Data Analyses;Data Set;Dedications;design;Development;Documentation;Dose Rate;dosimetry;Ensure;Epidemiology;Equity;experience;Experimental Designs;Extramural Activities;follow-up;Funding;Glioma;Goals;Grant;high standard;Human Resources;improved;Indiana;innovation;Institution;Interdisciplinary Study;irradiation;Laboratories;Lead;Leadership;Maintenance;Malignant Neoplasms;Manuscripts;Medical;medical schools;meetings;member;Mission;Modality;Monitor;Mus;Nature;neurobehavioral;Neurosciences;operation;Patient-Focused Outcomes;Personnel Management;Phase;Physics;Positioning Attribute;power analysis;Preparation;Principal Component Analysis;Process;professor;Prognosis;programs;Progress Reports;Protocols documentation;Publications;Radiation;Radiation Oncology;Radiation therapy;Radiobiology;Randomized;Reporting;Reproducibility;Research;Research Design;Research Personnel;Research Project Grants;Resources;Schedule;sex as a biological variable;Site;Source;Statistical Data Interpretation;symposium;System;Teleconferences;Testing;Therapeutic Index;Translational Research;Travel;United States National Institutes of Health;Universities;University adminstration;web site;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Rare Diseases;Tuberculosis

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

PHR: NARRATIVE Mycobacterium tuberculosis (Mtb) infection fate is the product of interactions between host and pathogen coordinated through biological networks. I will systematically dissect host signaling and Mtb gene regulatory network activities that impact Mtb viability and host inflammation during Mtb infection in primary human monocyte-derived macrophages (MDMs), a major infected host cell in vivo. This characterization will uniquely enable dissection of infection phenotypes in primary human host cells at an unprecedented scale and granularity, maximizing clinical relevance of biological insights.

PI_NAMEs: MA, SHUYI  (contact)

PROGRAM_OFFICER_NAME: MENDEZ, SUSANA

PROJECT_TERMS: analytical tool;Attenuated;Binding;Biological;Biological Assay;Bone Marrow;Cells;Cessation of life;clinically relevant;Data;design;Detection;Disease;Dissection;Drug Antagonism;Drug Synergism;empowerment;Equilibrium;Exposure to;FDA approved;Feedback;Future;Gene Expression Profile;gene regulatory network;Genes;Genetic;Genetic Transcription;Goals;Growth;Homeostasis;Human;Immunology;in vivo;Individual;Infection;Infection Control;Inflammation;Inflammatory;inhibitor;innovation;insight;interest;Intervention;Investigation;isoniazid;Joints;kinase inhibitor;Macrophage;Measures;Microbiology;Molecular;molecular dynamics;monocyte;Mus;Mycobacterium tuberculosis;novel;novel therapeutic intervention;novel therapeutics;Organism;Outcome;pathogen;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Pharmaceutical Preparations;Phenotype;Phosphotransferases;Physiological;Postdoctoral Fellow;predictive tools;programs;Regimen;Research;response;Rifampin;Signal Transduction;Stress;Symptoms;synergism;Testing;Therapeutic Effect;tool;tool development;transcription factor;Transcriptional Regulation;transcriptome;transcriptomic profiling;Treatment Protocols;Tuberculosis;tuberculosis drugs;tuberculosis treatment;Work

PROJECT_TITLE: Network Dissection of Host-Pathogen Interactions in Mycobacterium tuberculosis Infection


NIH_SPENDING_CATS: Bioengineering;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases

PHR: PROJECT NARRATIVE – DOSIMETRY, PHYSICS & MODELING CORE Glioblastoma multiforme (GBM) is the most common and deadliest form of brain cancer. The proposed program seeks to evaluate FLASH, a new radiation treatment paradigm that has shown strong promise for eradicating cancer cells with significantly less harm to surrounding healthy tissue than is possible with current radiotherapies. In this core, we will develop three key innovations that will enable the rapid translation of FLASH to the clinic, and provide a long-awaited breakthrough in the treatment of GBM.

PROJECT_TERMS: absorption;Address;Animal Experiments;Animals;Biological;Blood Vessels;Brain;Brain Neoplasms;Cancer Biology;cancer cell;Cancer Patient;cancer therapy;Canis familiaris;Clinic;Clinical;clinical application;clinical implementation;clinical practice;clinical translation;Clinical Trials;clinically relevant;Code;Cognition;conventional dosing;Coupled;Data;Data Set;Development;Dose;Dose Rate;dosimetry;Effectiveness;efficacy testing;Electrons;Emerging Technologies;Ensure;Future;Glioblastoma;Goals;high risk;Human;immunoregulation;in vivo;Indiana;Infrastructure;innovation;Institution;International;irradiation;Laboratories;Linear Accelerator Radiotherapy Systems;Malignant neoplasm of brain;Measurement;Measures;Medical;Modality;Modeling;multidisciplinary;Mus;neurobehavioral;Neurocognitive;Neurons;Normal tissue morphology;novel;novel strategies;Oncologist;Organ;organ injury;Outcome;Oxygen;Patients;Photons;Physics;pre-clinical;Pre-Clinical Model;preclinical imaging;preclinical study;prevent;Program Research Project Grants;programs;Radiation;Radiation Dose Unit;Radiation Injuries;Radiation Oncology;Radiation therapy;Radiobiology;Reproducibility;Research;Research Infrastructure;Roentgen Rays;Science;Scientist;Series;Site;success;System;Technology;Testing;Therapeutic;Therapeutic Index;Therapeutic Studies;Tissues;tool;Toxic effect;Translating;Translations;tumor;Universities;University Hospitals;Validation;Vertebral column

PROJECT_TITLE: Dosimetry, Physics & Modeling Core


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Mental Health;Neurosciences

ORG_CITY: Newark

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: PROJECT NARRATIVE Individuals with developmental language disorder (DLD) comprise ~7% of the U.S. population, and experience persistent difficulties with learning and memory into adulthood. This project seeks to advance our understanding of how to leverage the time of day of learning for the long-term retention of linguistic (speech) and non-linguistic category information in adults with and without DLD. This information will not only advance our understanding of learning and memory in adults with DLD, but will inform intervention practices for other disorders with compromised speech-sound representations (e.g. dyslexia, speech sound disorder).

PI_NAMEs: EARLE, FRANCES SAYAKO (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TITLE: Improving the retention of speech-perceptual learning in adults with and without language disorder

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Cancer;Brain Disorders;Cancer;Mental Health;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases

PHR: PROJECT NARRATIVE – Neurobehavioral Core (Core 3) Glioblastoma multiforme (GBM) is the most common and deadliest form of brain cancer. The proposed program seeks to evaluate FLASH, a new radiation delivery platform that has shown strong promise for eradicating cancer cells with significantly less harm to surrounding healthy tissue than is possible with current radiotherapies. This core will develop a unifying neurobehavioral testing platform that will determine the effects of FLASH and conventional radiation therapies on learning, memory and mood, multifaceted endpoints critical to therapeutic outcome.

PROJECT_TERMS: Animals;Anxiety;Behavior assessment;behavior test;Behavioral;Behavioral Paradigm;Blood Vessels;Brain;Brain Neoplasms;cancer cell;cancer therapy;Canis familiaris;Clinic;Clinical;clinical practice;Clinical Trials;Cognition;Cognitive;cohort;Collection;Combined Modality Therapy;Confounding Factors (Epidemiology);conventional dosing;Coupled;Darkness;Data;data dissemination;Data Set;design;Dose Rate;dosimetry;Ensure;exosome;experience;Extinction;Female;field study;flexibility;forced swim test;Fright;Genetic;Glioblastoma;Goals;Guidelines;Human;immunoregulation;Impaired cognition;Indiana;innovation;Interdisciplinary Study;irradiation;Learning;Light;Location;male;Malignant neoplasm of brain;Memory;Mental Depression;Modality;Moods;Motor Activity;Mus;neurobehavioral;neurobehavioral test;Neurocognitive;neurocognitive test;Neurons;Normal tissue morphology;novel;object recognition;Oncologist;Outcome;Oxygen;Patients;performance site;pharmacologic;Physics;preclinical study;Procedures;programs;Protocols documentation;Radiation;radiation delivery;Radiation Injuries;Radiation Oncology;Radiation therapy;Reproducibility;Research;Research Activity;Schedule;Series;Services;Shipping;Side;Site;Social Interaction;Specific qualifier value;Standardization;stem cells;Technology;Test Result;Testing;Therapeutic Index;therapy outcome;Time;Tissues;Translating;Translations;Treatment Protocols;tumor;Tumor Burden;Universities;Update

PROJECT_TITLE: Neurobehavioral Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Genetics;Hematology;Orphan Drug;Rare Diseases

ORG_NAME: FRED HUTCHINSON CANCER CENTER

PHR: NARRATIVE Mutations affecting RNA splicing factors are common across many cancers, with particularly high frequencies in disease types with few effective, FDA-approved treatments. New therapies to treat these diseases are urgently needed. Here, we will create new precision therapeutics that selectively target and eliminate cells carrying cancer-causing mutations affecting RNA splicing factors.

PI_NAMEs: ABDEL-WAHAB, OMAR ;BRADLEY, ROBERT K (contact)

PROGRAM_OFFICER_NAME: SALOMON, RACHELLE

PROJECT_TERMS: 3' Splice Site;Acute Myelocytic Leukemia;Address;Affect;Alleles;Anatomy;Biomedical Engineering;Biotechnology;Breast Cancer Cell;Cancer Biology;cancer cell;Cancer Patient;cancer type;cell killing;cell type;Cells;Chronic Myelomonocytic Leukemia;Clinical;clinical phenotype;conventional therapy;Disease;Dissection;Drug Delivery Systems;Dysmyelopoietic Syndromes;efficacy evaluation;Elements;Engineering;Event;Exons;experimental study;FDA approved;Frequencies;functional genomics;Ganciclovir;Gene Expression;Growth;Health;Hematologic Neoplasms;Hematological Disease;Hematopoietic;Hematopoietic Neoplasms;immunostimulatory therapy;In Vitro;in vivo;Individual;insight;Interleukin-15;Introns;Left;Lesion;leukemia;Leukemic Cell;lipid nanoparticle;loss of function;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Melanoma;Melanoma Cell;Messenger RNA;Methods;Molecular;mutant;Mutate;Mutation;Myeloid Leukemia;Myeloproliferative disease;Nature;neoplasm relapse;new technology;novel therapeutics;Patient Care;Patients;Pattern;Pharmaceutical Preparations;Physicians;Precision therapeutics;Production;protein expression;Proteins;Recurrence;Refractory;RNA Splicing;Safety;Scientist;selective expression;side effect;Simplexvirus;Solid Neoplasm;Spliceosomes;SRSF2 gene;suicide gene;System;Technology;Testing;Therapeutic;therapeutic protein;therapeutic target;Thymidine Kinase;Tissues;tumor;tumorigenic;Work;Xenograft procedure

PROJECT_TITLE: Synthetic introns for selective targeting of RNA splicing factor-mutant leukemia

STUDY_SECTION: DMPC

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology C Study Section[DMPC]


ADMINISTERING_IC: TW

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Data Science;Dissemination and Implementation Research;Eye Disease and Disorders of Vision;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: MBARARA

ORG_COUNTRY: UGANDA

ORG_FIPS: UG

ORG_NAME: MBARARA UNIVERSITY/SCIENCE/ TECHNOLOGY

PHR: Overall Research Plan Project Narrative Medical images offer great potential for supporting clinical diagnosis and care management; however, their utility for African researchers and clinicians are limited by the number of images available, insufficient linkage to relevant clinical data, limited data from African populations for proper image interpretation, and poor implementation in clinical practice. The Mbarara University Data Science Research Hub is designed to overcome these barriers through robust Data Management and Analysis and Administrative Cores, initially supporting projects in posterior segment eye disease and cervical cancer with plans for expansion to new projects and sites, as well as training in data science and implementation science.

PI_NAMEs: CELI, LEO ANTHONY G;HABERER, JESSICA ELIZABETH;KAGGWA, FRED  (contact)

PROGRAM_OFFICER_NAME: NEWSOME, BRAD

PROJECT_TERMS: Academia;Accounting;Address;Africa;Africa South of the Sahara;African;algorithm development;Artificial Intelligence;artificial intelligence algorithm;Attention;Calibration;Cancer Detection;care delivery;Cellular Phone;Central Africa;Cervical;Cervix Uteri;Clinical;clinical care;Clinical Data;clinical database;clinical diagnosis;clinical practice;clinically relevant;Collaborations;Collection;college;community organizations;computerized data processing;Computerized Medical Record;Data;Data Analyses;data exchange;data harmonization;data infrastructure;data integration;Data Linkages;data management;data quality;Data Science;Data Security;Dermatology;design;Development;Diabetic Retinopathy;Diagnosis;Disease;Eastern Africa;Ecosystem;Ensure;Equipment;Eye diseases;Fostering;Funding;fundus imaging;Future;General Hospitals;Ghana;Goals;Grant;Health;health care delivery;Health Policy;Health Priorities;Health system;Healthcare;Image;Image Analysis;implementation science;improved;Individual;innovation;Institution;Kenya;Knowledge;Label;Machine Learning;Macular degeneration;Malignant neoplasm of cervix uteri;Managed Care;Massachusetts;Medical Imaging;Methodology;Methods;Mission;multidisciplinary;Nongovernmental Organizations;open data;Ophthalmologist;Outcome;Pathway interactions;Patients;Policy Maker;Policy Making;Population;Positioning Attribute;Posterior eyeball segment structure;programs;quality assurance;Quality Control;Radiology Specialty;Research;Research Personnel;Research Project Grants;Resource Allocation;Resources;Role;Science;Site;skills;Southern Africa;Surveys;symposium;Techniques;Technology;technology diffusion;Training;Translating;Uganda;United States National Institutes of Health;Universities;uptake;Work

PROJECT_TITLE: MUST Data Science Research Hub (MUDSReH)

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


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: STANFORD

ORG_DEPT: BIOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative The subject of this project—mapping genotype to phenotype—is of great importance to biomedicine. For example, mutations are a major source of human disease, and understanding how genetic variants impact fitness in a model organism may shed light on these relationships in humans as well.

PI_NAMEs: FRASER, HUNTER B (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Affect;Alleles;Automobile Driving;base;Binding Sites;Biology;Characteristics;Code;Data;Environment;Evolution;Experimental Designs;experimental study;fitness;gene environment interaction;Gene Frequency;Genes;Genetic;Genetic Polymorphism;Genetic Transcription;genetic variant;Genetic Variation;Genome;genome editing;genome-wide;Genomics;Genotype;Goals;Human;human disease;insight;Maps;Measures;Minor;model organism;Molecular;Mutagenesis;Mutation;Natural Selections;novel strategies;Open Reading Frames;Organism;Pattern;Phenotype;Play;Point Mutation;precise genome editing;Process;promoter;Property;rare variant;Research;Resolution;Ribosomes;Role;Saccharomyces cerevisiae;Saccharomycetales;segregation;Shapes;Single base substitution;Source;System;Technology;theories;transcription factor;Variant;Yeasts

PROJECT_TITLE: Evolutionary Genomics of Yeast

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-B(02)M]


ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE Cells constantly need to destroy membrane proteins, either because they are damaged or no longer needed. Failure to do this properly can lead to a variety of human health ailments such a neurodegenerative diseases and cancer. This proposal seeks to understand the different pathways that membrane proteins use to undergo degradation.

PI_NAMEs: PIPER, ROBERT C (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Ablation;ATP phosphohydrolase;Binding;Binding Sites;Biological;Biological Process;Cell surface;cell type;Cells;Chemicals;Chimeric Proteins;Complex;Data;Defect;Degradation Pathway;Dislocations;Endoplasmic Reticulum;Endosomes;examination questions;exosome;extracellular vesicles;Failure;Family;Goals;Health;Human;human disease;Knowledge;Lead;Learning;Link;Lysine;Lysosomes;Malignant Neoplasms;Mediating;member;Membrane;Membrane Proteins;misfolded protein;Molecular;molecular array;multicatalytic endopeptidase complex;Multivesicular Body;mutant;Neurodegenerative Disorders;Organism;Outcome;Pathway interactions;Peptide Hydrolases;Polyubiquitin;posters;Process;protein degradation;Protein Family;protein folding;Protein Sortings;Proteins;proteostasis;proteotoxicity;Publishing;Quality Control;receptor;Scheme;Sorting;Specific qualifier value;Stress;Structure;System;theories;therapeutic development;Therapeutic Intervention;trans-Golgi Network;Ubiquitin;Vesicle;Work;Yeasts

PROJECT_TITLE: Ubiquitin-dependent sorting in endosomes and the TGN

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Infectious Diseases

ORG_CITY: HACKENSACK

ORG_NAME: HACKENSACK UNIVERSITY MEDICAL CENTER

ORG_STATE: NJ

PHR: CD8+ T lymphocytes are essential players in mounting protective cellular immune responses against pathogens and malignantly transformed cells. This proposal will mechanistically elucidate the dynamic interplay of genome organizers and chromatin architecture in programming CD8+ T cell homeostasis and differentiation to memory CD8+ T cells in response to viral infection and tumor microenvironment. Our proposed studies will lead to paradigm-shifting advances in scientific knowledge, and provide novel insights into devising more effective vaccines and therapeutics for infectious diseases and cancers.

PI_NAMEs: PENG, WEIQUN ;XUE, HAI-HUI  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: 3-Dimensional;Adoptive Cell Transfers;Algorithms;antiviral immunity;Architecture;Binding;Biological Assay;CD8-Positive T-Lymphocytes;CD8B1 gene;cell transformation;Cells;Cellular biology;chimeric antigen receptor;chimeric antigen receptor T cells;Chromatin;Communicable Diseases;cytokine;cytotoxic;Development;Elements;Engineered Gene;engineered T cells;epigenetic regulation;flexibility;Follow-Up Studies;Foundations;frontier;Funding;Gene Expression Regulation;Genome;genome-wide;Genomics;Goals;Homeostasis;IL7 gene;Immune response;Immunocompetence;Immunotherapy;improved;in vivo;inducible gene expression;Infiltration;insight;Interleukin-15;Knowledge;Link;Malignant - descriptor;Malignant Neoplasms;Mature T-Lymphocyte;Mediating;Memory;Molecular;Molecular Analysis;Multiomic Data;Nature;novel;Output;pathogen;Pathway interactions;Pattern;Preventive vaccine;Progress Reports;Proliferating;rational design;Regulation;Research;Research Design;Resolution;response;Role;SELL gene;Shapes;stem;Supervision;Systems Biology;T cell differentiation;T-Lymphocyte;Therapeutic;Thymus Gland;transcription factor;Transcriptional Regulation;tumor;Tumor Antigens;Tumor Immunity;tumor microenvironment;Vaccines;Viral;Viral Antigens;Viral Cancer;Virus Diseases

PROJECT_TITLE: CTCF in CD8 T cell homeostasis and anti-viral/tumor immunity


ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE The objective of this study is to determine how the oocyte modifies its calcium signaling machinery in preparation for fertilization. The findings could lead to treatments that improve oocyte quality during in vitro fertilization, thereby improving fertility in humans and domestic animals. This study will also explore how maternal aging impacts the oocyte calcium signaling machinery and how this correlates with inadequate egg activation which is common in oocytes from aged females.

PI_NAMEs: CHRISTENSON, LANE K. (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Actins;advanced maternal age;age effect;age related;aged;Aging;assisted reproduction;Assisted Reproductive Technology;Binding;Binding Sites;biological adaptation to stress;Calcium Signaling;Cell membrane;Cells;Competence;confocal imaging;Confocal Microscopy;contraceptive target;Defect;Deterioration;Development;Docking;Domestic Animals;egg;Endoplasmic Reticulum;endoplasmic reticulum stress;Event;Exhibits;experimental study;Failure;Female;Fertility;fertility improvement;Fertilization;Fertilization in Vitro;Human;Immunofluorescence Microscopy;Impairment;improved;in vivo;Injections;Intracytoplasmic Sperm Injections;Ionophores;Knockout Mice;Macaca mulatta;Mammals;Maps;Maternal Age;Mediating;Modeling;Mus;novel;old mice;oocyte maturation;oocyte quality;Oocytes;Patients;Positioning Attribute;postnatal development;Preparation;Procedures;Process;Proteins;Protocols documentation;Regulation;reproductive;response;Risk;Role;Signal Transduction;Signaling Protein;sperm cell;Sperm Head;sperm protein;Sperm-Ovum Interactions;spermadhesin;Structural defect;Structure;Testing;transcriptome;ultra high resolution;Work

PROJECT_TITLE: Fertilization-induced maturation of cortical ER clusters in oocytes; impact of maternal age

STUDY_SECTION: CMIR

STUDY_SECTION_NAME: Cellular, Molecular and Integrative Reproduction Study Section[CMIR]


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: The proposed work will investigate the molecular structure and mechanism of action of a group of kinesin proteins that modulate the ability of the microtubular cytoskeleton to elongate and shrink. Due to the role that these kinesins have in cell division and tumor growth they are also attractive targets for the development of anti-cancer drugs. Thus, the proposed studies may help the rational design of a new generation of drugs to treat cancer and human diseases associated with kinesin malfunction (kinesinopathies).

PI_NAMEs: SOSA, HERNANDO JOSE (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: 3-Dimensional;Address;Affect;Antineoplastic Agents;ATP Hydrolysis;Binding;Biological Assay;cancer therapy;Cell division;Cell Physiology;Centrioles;Cilia;Classification;comparative;Complex;Coupling;Cryoelectron Microscopy;Cytokinesis;Cytoskeletal Proteins;Cytoskeleton;Data;depolymerization;Development;dimer;Elements;Family;Family member;Generations;Grant;human disease;Hydrolysis;Kinesin;Knowledge;Length;Malignant Neoplasms;member;Microtubule Depolymerization;Microtubule Polymerization;Microtubules;Mitosis;Molecular;Molecular Conformation;Molecular Mechanisms of Action;Molecular Structure;Motility;Motor;Movement;Mutate;neurodevelopment;Nucleotides;optic trap;optical traps;Pharmaceutical Preparations;Play;Power stroke;prevent;Proteins;rational design;Regulation;Reporting;Resolution;Role;Structure;Testing;therapeutic target;transmission process;Tubular formation;Tubulin;tumor growth;Work

PROJECT_TITLE: Mechanism of Microtubule Dynamics Regulation by Kinesins