NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: Project Narrative Our study of the mechanisms of nematode molting can impact public health in two areas. Processes conserved in humans, such as extracellular matrix remodeling and oscillatory gene expression, could provide insight into human disease and development. Nematode-specific mechanisms are strong candidates to target for developing therapeutics against parasitic nematodes, a class of organisms that infect over one billion people and threaten food security through infesting livestock and crops.

PI_NAMEs: WARD, JORDAN DAVID (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Address;Affect;Animals;Area;Arthropods;Bacteria;Behavior;Binding;Biochemical;Biogenesis;Biological;Biological Assay;Biological Process;Biology;Caenorhabditis elegans;cancer cell;candidate identification;Cells;Cholesterol;Circadian Rhythms;Clock protein;Collagen;combat;Defect;Dermal;design;Development;Developmental Process;Diet;dietary;Ecdysone;Ensure;Environment;exoskeleton;experimental study;Extracellular Matrix;Feedback;food security;Foundations;Future;Gene Expression;gene function;gene regulatory network;Genes;Genome;genome editing;Goals;Growth;Homologous Gene;Hormonal;hormonal signals;hormone regulation;Hormones;Hour;Human;Human Development;human disease;Insecta;insight;interest;Intervention;Invaded;leucine-rich repeat protein;Ligand Binding;Ligands;Light;Livestock;Mammals;Messenger RNA;MicroRNAs;Modeling;Molecular;Molting;Monitor;Mutation;neglected tropical diseases;Nematoda;Nematode infections;novel;Nuclear Hormone Receptors;Organism;Orthologous Gene;Parasitic nematode;Pattern;Peptide Hydrolases;Persons;pharmacologic;Physiology;prevent;Process;Protease Inhibitor;Proteins;Public Health;Research;Series;Signal Transduction;Signaling Molecule;Skin;Sleep;Stereotyping;steroid hormone;Steroids;Structure;Sulfate;System;Testing;Therapeutic;Time;trafficking;trait;transcription factor;Tumor Cell Invasion;Work;wound healing;Zona Pellucida

PROJECT_TITLE: Mechanisms of nematode molting

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences

ORG_CITY: SALT LAKE CITY

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROSCIENCES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE The neurotransmitter dopamine is crucial for the proper execution of locomotor behaviors. This project will determine how a previously overlooked population of dopamine-producing neurons in the vertebrate brain controls movement through its neural targets. The outcome of these experiments will be a better understanding of the diverse means by which the brain generates behaviors appropriate to an animal’s environment.

PI_NAMEs: DOUGLASS, ADAM D (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TITLE: Functional architecture of dopamine signaling within a zebrafish sensorimotor network

STUDY_SECTION: SMN

STUDY_SECTION_NAME: Sensory-Motor Neuroscience Study Section[SMN]


ADMINISTERING_IC: GM

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: BOSTON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: TUFTS UNIVERSITY BOSTON

ORG_STATE: MA

PHR: Project Narrative Improving public health and fostering future leaders who can meet the unknown future challenges and unmet needs in health care requires the training of individuals who will incorporate contemporary medical knowledge and best practices, and also will explore the fundamental, scientific and evidential basis of medicine. Our program trains MD-PhD students to become the physician-scientist leaders who will expand the frontiers of medicine and science, thereby identifying new paradigms for the diagnosis, prevention and treatment of human disease. Through our program, students acquire the lifelong skills in medicine, science and personal resilience needed to understand the mechanisms underlying disease, resolve key healthcare issues and drive innovative biomedical research over the course of their careers, thereby improving the health and well-being of current and future generations.

PI_NAMEs: CHIN, MICHAEL T (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TITLE: Medical Scientist Training Program at Tufts University

STUDY_SECTION: TWD

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Urologic Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE We have previously developed a computer decision support system for (CDSS-T) for monitoring of bladder cancer treatment response. If successfully deployed and utilized, CDSS-T will be a useful tool to aid clinicians in improving the accuracy and reproducibility of tumor treatment response assessment. Improving the reliability in assessment of treatment response to neoadjuvant therapy at an early stage is vital for identifying patients who do not respond to preserve their physical condition, thus allowing them to seek alternative treatment, which may reduce morbidity and improve the quality of life of patients suffering from bladder cancer. In addition, the multi-site pilot clinical trial will provide an excellent opportunity to experience the process of bringing laboratory research from bench to bedside, which will serve as a valuable guide for future development of clinically practical tools for various diseases.

PI_NAMEs: ALVA, AJJAI SHIVARAM;HADJIYSKI, LUBOMIR M (contact)

PROGRAM_OFFICER_NAME: TATA, DARAYASH B

PROJECT_TERMS: Adjuvant Chemotherapy;alternative treatment;bench to bedside;Biological Markers;Bladder;Bladder Neoplasm;Cancer Etiology;cancer imaging;cancer type;Cessation of life;Characteristics;chemotherapy;Clinical;Clinical assessments;clinical care;clinical decision support;clinical development;clinical research site;Clinical Treatment;Clinical Trials;Collaborations;Computers;Data;Decision Support Systems;design;Diagnosis;Disease;effectiveness validation;Ensure;Evaluation;experience;Feedback;Future;Goals;Image;Image Analysis;improved;innovation;Interobserver Variability;Laboratory Research;Machine Learning;Malignant neoplasm of urinary bladder;men;Monitor;Morbidity - disease rate;mortality;Neoadjuvant Therapy;Oncologist;Outcome;outcome prediction;Output;Patient Care;Patients;Performance;predictive modeling;preservation;Process;prospective;Quality of life;quantitative imaging;Radical Cystectomy;radiologist;radiomics;Reproducibility;responders and non-responders;response;Site;support tools;System;Techniques;Testing;Time;tool;Training;treatment response;tumor;Tumor Volume;United States;Woman

PROJECT_TITLE: Biomarker-Based Tools for Treatment Response Decision Support of Bladder Cancer


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative The intracellular pathogen Shigella flexneri is the causative agent of Bacillary dysentery, a severe form of diarrheal disease associated with massive destruction of the intestinal mucosa and presence of blood in stool. We have recently developed a unique small animal model of shigellosis in infant rabbits. Here, we propose to develop Transposon-sequencing approaches to identify the bacterial factors that support Bacillary dysentery.

PI_NAMEs: AGAISSE, HERVE F (contact);CAMILLI, ANDREW

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Actins;Address;Agreement;Animal Model;Animals;Bacteria;bacterial fitness;Blood;Blood Vessels;cell type;Cells;Cessation of life;Collaborations;Colon;Complex;Cytoskeleton;Cytosol;Data;Development;diarrheal disease;Disease;Dysentery;enteric pathogen;Epithelial Cells;Epithelium;experience;experimental study;Feces;fitness;Genes;Grant;Hemorrhagic colitis;Histology;Hour;Human;Immune;immune cell infiltrate;Immune system;In Vitro;in vivo;Individual;Infant;Infection;Inflammation;intestinal epithelium;Intestinal Mucosa;Invaded;Investigation;Lamina Propria;Lesion;Location;Membrane;Modeling;Motility;Mucous Membrane;mutant;nonhuman primate;Oryctolagus cuniculus;Outcome;pathogen;Pathogenesis;Phase;Phenotype;Plasmids;Process;Proteins;Role;Seminal;Shigella flexneri;Shigella Infections;success;Survival Rate;Symptoms;System;Techniques;Testing;tissue culture;transposon sequencing;Type III Secretion System Pathway;Ulcer;uptake;Vacuole;Virulence;Virulence Factors

PROJECT_TITLE: Characterization of virulence factors in shigellosis


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

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

ORG_CITY: RIVERSIDE

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

ORG_STATE: CA

PHR: Project Narrative The objective of our proposed MIRA program is to develop novel statistical methods for multiscale analysis of single-cell transcriptomes. Our program will address the critical need for statistical and computational tools that can accurately evaluate biological hypotheses for single cell populations at different scales, from cells to genes to RNA molecules. The successful completion of our proposed research will provide efficient and broadly applicable statistical and bioinformatics tools for generating substantial insights into the identification of key cells, pathways, gene interactions, and RNA transcripts associated with various biological contexts, including human disease.

PI_NAMEs: LI, WEI VIVIAN  (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Address;Bioinformatics;bioinformatics tool;Biological;Biology;Biotechnology;Cancer Biology;Cancer Institute of New Jersey;cell type;Cells;Computer software;computerized tools;Computing Methodologies;Data;Data Science;denoising;design;Development;Disease;Disease Progression;experimental study;Foundations;Gene Expression;gene interaction;Genes;Genetic Transcription;genomic data;Goals;Health;High-dimensional Modeling;human disease;improved;innovation;insight;Intestines;Knowledge;Measurement;Methods;Molecular Profiling;Neurobiology;novel;Pathway interactions;Patients;Polyadenylation;Population;Post-Transcriptional Regulation;posttranscriptional;programs;Research;Resolution;RNA;Sampling;single cell analysis;single-cell RNA sequencing;Statistical Methods;Statistical Models;Structure;Tissues;Transcript;transcriptome;user friendly software;Work

PROJECT_TITLE: Novel Statistical Methods for Multiscale Analysis of Single-cell Transcriptomes

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: NORTH DARTMOUTH

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS DARTMOUTH

PHR: PROJECT NARRATIVE: Human CD4 receptors are potent inhibitors of HIV-1 infection and are antagonized by the virus through a se- ries of stringent, well-coordinated mechanisms. This project is designed to elucidate the details of these mech- anisms. Once completed, this work should reveal opportunities for developing novel antiretrovirals, which can restore CD4 in infected cells and thus unleash its inhibitory power to combat HIV-1 infection.

PI_NAMEs: JIA, XIAOFEI  (contact)

PROGRAM_OFFICER_NAME: SHANKAR, UDAY K

PROJECT_TERMS: Affinity;Anti-Retroviral Agents;antiretroviral therapy;Back;base;beta-Transducin Repeat-Containing Proteins;Binding;Biochemical;CD4 Antigens;CD4 Positive T Lymphocytes;Cell surface;Cells;Chemicals;Clathrin;Clathrin Adaptors;combat;Complex;crosslink;Cryoelectron Microscopy;Crystallography;Cullin Proteins;Cytoplasmic Tail;Data;Degradation Pathway;design;Development;Down-Regulation;drug discovery;Drug resistance;Endocytosis;Endoplasmic Reticulum;Endosomes;enhancer-binding protein AP-2;Event;Excision;experience;HIV;HIV Infections;HIV Receptors;HIV-1;Human;Immune;immune clearance;Immune response;improved;In Vitro;Individual;Infection;inhibitor;insight;Integration Host Factors;Knowledge;Laboratories;Literature;Lysosomes;Mediating;Molecular;molecular assembly/self assembly;multicatalytic endopeptidase complex;Multivesicular Body;nef Protein;novel;novel therapeutics;Pathway interactions;Pharmaceutical Preparations;Play;Polyubiquitination;protein transport;Proteins;recruit;Resolution;Role;Secure;Series;side effect;Structure;Substrate Interaction;Surface;Testing;Therapeutic;trafficking;trans-Golgi Network;Transcription Factor AP-1;ubiquitin-protein ligase;Variant;Vesicle;Viral;Viral Proteins;viral rebound;Virion;Virus;Virus Inhibitors;Virus Replication;vpu Protein;Work

PROJECT_TITLE: Elucidating the Structural Bases of HIV-1-Induced CD4 Degradation

STUDY_SECTION: HVCD

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


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Dental, Oral, and Craniofacial Disease

ORG_CITY: BIRMINGHAM

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE Our nation is faced with a growing shortage of highly qualified, well-trained clinician scientists and scientists to address the expanding dental, oral and craniofacial health needs of our diverse population. The Dental Academic Research Training (DART) Program is a comprehensive research-training program focused on an innovative, integrated, multi-disciplinary approach to produce a cadre of well-trained, skilled, collaborative scientists and clinician scientists that are capable to address the critical dental, oral and craniofacial research issues of our nation. The program is housed in the University of Alabama at Birmingham School of Dentistry, ranked among the top ten in NIDCR funding (dental school and institution), which is an integral component of a vital major health science center with a “Highest Research Activity” Carnegie Classification located in the southeast region of our nation.

PI_NAMEs: JAVED, AMJAD  (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: Address;Alabama;Basic Science;Biocompatible Materials;Biomimetics;career;Classification;Clinical;Clinical Research;craniofacial;Dental;Dental caries;Dental General Practice;Dentists;design;Development;Development Plans;Developmental Biology;Doctor of Philosophy;Environment;experience;Funding;Genetic;graduate student;Grant;Health Professional;Health Sciences;Immunology;implementation science;innovation;interdisciplinary approach;Interdisciplinary Study;Knowledge;Leadership;Malignant Neoplasms;Microbiology;National Institute of Dental and Craniofacial Research;next generation;Oral;Oral health;orofacial;Outcomes Research;Pathway interactions;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;practice-based research network;pre-doctoral;Productivity;professional students;Research;Research Activity;Research Training;responsible research conduct;School Dentistry;Science;Scientist;skill acquisition;skills;Students;Training;Training Programs;Translational Research;Universities;Writing

PROJECT_TITLE: Dental Academic Research Training Program (DART)


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Infectious Diseases;Microbiome;Nutrition;Precision Medicine;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative South Asia is one of the most populous regions in the world, comprising thousands of populations, with complex demographic histories and disease landscape; yet, it is underrepresented in the genomic literature. This diverse research program integrates ancient and modern genome-wide data to reconstruct the genetic history of South Asians and their infectious diseases, and the impact of lifestyle-induced dietary transitions on the gut microbiome and human health of Indian populations. Ultimately, insights from this research can aid in dissecting the basis of differential disease susceptibilities among South Asians and inform precision medicine efforts in the region.

PI_NAMEs: RAGHAVAN, MAANASA  (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Admixture;Asia;Asian ancestry;Asian population;burden of illness;Communicable Diseases;Complex;Data;Detection;Diet;dietary;Disease;Disease susceptibility;Event;Evolution;Exhibits;Gene Pool;Genes;Genetic;genetic evolution;Genetic Structures;genome-wide;Genomic approach;genomic data;Genomics;gut microbiome;Health;Historical Demography;Human;India;Individual;insight;Life Style;Light;Literature;Microbe;microbiome composition;migration;Modernization;Native-Born;pathogen;Phylogenetic Analysis;Population;precision medicine;Process;programs;Recording of previous events;Research;skeletal;social culture;social structure;South Asian

PROJECT_TITLE: Reconstructing the evolutionary history of humans and human-associated microbes in South Asia using an integrated genomics approach

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


NIH_SPENDING_CATS: Clinical Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative We will evaluate the mechanisms whereby antibody-producing plasma cells succumb to or develop resistance to drugs that inhibit proteasome function. Our results should reveal novel strategies to deplete problematic plasma cells, and hence improve outcomes in transplantation and autoimmunity.

PI_NAMEs: ALLMAN, DAVID M (contact);HILDEMAN, DAVID A;WOODLE, ERVIN STEVE

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Acute;Affect;Alloantigen;antagonist;Antibodies;Antibody titer measurement;Antigens;Apoptosis;Apoptotic;Area;Autoimmunity;Automobile Driving;BIM Bcl-2-binding protein;Biochemical;Bone Marrow;Bortezomib;Cell Death;Cell Physiology;Cell Survival;Cellular biology;Cessation of life;Chronic;Data;Disease;Drug resistance;Drug usage;endoplasmic reticulum stress;experience;Family member;Flow Cytometry;Fostering;Gene Expression;Gene Expression Profile;Genes;HIF1A gene;Homeostasis;Human;Hypoxia;Immunoglobulin-Secreting Cells;improved;improved outcome;Induction of Apoptosis;ineffective therapies;insight;Isoantibodies;Life;Maintenance;MCL1 gene;Mediating;Memory B-Lymphocyte;Mitochondria;multicatalytic endopeptidase complex;Mus;mutant;Mutation;Natural Resistance;Natural Selections;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Organ;Pathway interactions;Patients;Pharmaceutical Preparations;Plasma Cells;Plasma Enhancement;Play;Population;prevent;Proteasome Inhibition;Proteasome Inhibitor;Publishing;Regulatory Pathway;Reporter;Resistance;Resistance development;resistance mechanism;response;restraint;Role;success;Testing;Tissue Donors;transcription factor;transcriptomics;Transplantation;Work

PROJECT_TITLE: Proteasome targeting for alloreactive plasma cells

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


NIH_SPENDING_CATS: Cancer;Genetics;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: Columbus

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Richter’s transformation (RT) is a morphologic change of chronic lymphocytic leukemia (CLL) to an aggressive llymphoma for which no effective therapies exist and all patients rapidly die from. Our preliminary data support the existence of novel biomarkers of transformation in the era of targeted therapies that could present an opportunity to treat CLL with a different approach that may prevent this complication. We employ a comprehensive approach to characterize both CLL prior to developing RT and also RT in the era of targeted therapies and seek to initiate the very first phase 1b/2 trial with BRD4 inhibitor PLX51107 combined with ibrutinib in CLL patients at high risk for RT and also in RT.

PI_NAMEs: LAPALOMBELLA, ROSA  (contact)

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Address;Aftercare;Agammaglobulinaemia tyrosine kinase;Allogenic;BCL2 gene;Biological Assay;Biological Markers;Bromodomains and extra-terminal domain inhibitor;c-myc Genes;Chronic Lymphocytic Leukemia;Clinical;Clinical Trials;clinically significant;cohort;Complex;Complication;Confidence Intervals;CRISPR screen;Data;Development;Diagnosis;Disease;Disease Progression;driver mutation;effective therapy;Epigenetic Process;follow-up;founder mutation;Frequencies;Future;Gene Mutation;Genes;Genomics;Goals;high risk;human model;Immune;Immuno-Chemotherapy;Immunologics;in vivo;inhibitor;inhibitor therapy;innovation;Institution;Karyotype;Knowledge;large cell Diffuse non-Hodgkin's lymphoma;Lesion;Long-Term Survivors;Lymphoma;Methods;Modeling;Morphology;mouse model;Mutation;NOTCH1 gene;novel;novel marker;Ohio;Outcome;participant enrollment;Pathway interactions;patient subsets;Patients;Pharmacodynamics;Phase;Phase Ib/II Trial;Phenotype;pre-clinical;prevent;Prevention;Relapse;Reporting;Resistance;Risk Factors;Sampling;Series;Stem cell transplant;targeted treatment;Testing;Tetraploidy;Therapeutic;Time;TP53 gene;Translating;Translational trial;treatment effect;treatment risk;tumor;Tyrosine Kinase Inhibitor;Universities;Work

PROJECT_TITLE: Understanding Richter's Transformation in the targeted therapies era

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


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

ORG_CITY: ATLANTA

ORG_DEPT: BIOLOGY

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Human development and survival depends greatly on how and when individual cells decide to proliferate, lay dormant, or carry out specialized functions. Congenital syndromes, cancer, and other cell diseases occur when there is a breakdown in the regulation of these behaviors in specific cells. We will use the small, transparent embryos of Ciona, one of the invertebrates most closely related to humans, to better understand which genes are activated to regulate behaviors that allow certain cells to survive and proliferate during the remarkable remodeling of the animal during metamorphosis from the larval to the adult phase.

PI_NAMEs: STOLFI, ALBERTO  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Adult;adult stem cell;Aging;Animals;Apoptosis;Apoptotic;Behavior;Binding;Binding Proteins;Biochemical;Biochemical Pathway;Biological;Biological Assay;Biological Metamorphosis;Biological Process;Cell Compartmentation;Cell Death;cell growth regulation;Cell Lineage;Cell Proliferation;Cell Reprogramming;cell type;Cells;Cellular Structures;Chordata;Complex;CRISPR/Cas technology;Development;developmental plasticity;Disease;Embryo;Embryonic Development;Equilibrium;Fibroblast Growth Factor;Fluorescence Microscopy;Gene Expression Regulation;gene function;Genes;genetic architecture;Genetic Transcription;genome editing;Genomics;Goals;Heavy Metals;hindbrain;Homologous Gene;Human;Human Development;human disease;In Vitro;in vivo fluorescence;Individual;Injury;innovation;intercalation;Invertebrates;knockout gene;Knowledge;Larva;Life;Life Cycle Stages;Link;Maintenance;Malignant Neoplasms;Marine Invertebrates;Metabolic;Metalloproteins;Midbrain structure;Modeling;Molecular;Motility;Natural regeneration;Neck;Nervous System;new technology;next generation sequencing;Nitric Oxide;Nitric Oxide Pathway;novel therapeutics;Organ;Outcome;Oxidants;Pathway interactions;Pattern;Phase;Population;Process;Proliferating;Property;Proteins;Regulation;Research;Role;sedentary;Signal Pathway;Signal Transduction;Sister;smoothened signaling pathway;Specific qualifier value;stem cells;Stereotyping;Structure;Swimming;Syndrome;Testing;Tissues;tool;Transcript;Undifferentiated;Up-Regulation;Urochordata;Vanadium;Vertebrates;Work

PROJECT_TITLE: Specification and maintenance of quiescent progenitor cells set aside for the biphasic life cycle of an invertebrate chordate

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


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

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative RNA viruses represent an existing and emerging threat to US public health. The proposed studies will create important knowledge that should contribute to development of strategies to treat and to prevent RNA viral infections, including those of current concern: ebola virus, enterovirus D68, and Severe acute respiratory syndrome coronavirus. Achievement of the goals of the application will provide novel targets and mechanisms for development of vaccines and inhibitors to prevent and to treat infections by RNA viruses.

PI_NAMEs: ARNOLD, JAMIE JON;CAMERON, CRAIG E. (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Achievement;Active Sites;Amino Acids;Anti-viral Agents;Attenuated;base;Base Pairing;Biochemical;Biological;Biological Assay;Biological Models;Biological Process;Biology;biophysical analysis;biophysical properties;Biophysics;Bypass;Cells;Complex;Defect;Development;DNA;Ebola virus;Enterovirus;Enterovirus 68;Enterovirus 71;epitranscriptome;Evolution;Frequencies;Genetic;Genetic Drift;genetic manipulation;Genetic Recombination;Genome;Goals;Guanine;Human poliovirus;In Vitro;in vitro Assay;in vivo;Individual;inhibitor;insight;Knowledge;Laboratories;Link;Mediating;Modeling;Modification;mutant;Mutation;novel;Nucleotides;pharmacologic;Polymerase;Positioning Attribute;posttranscriptional;prevent;Process;Property;Public Health;reconstitution;RNA;RNA Virus Infections;RNA Viruses;RNA-Directed RNA Polymerase;SARS coronavirus;Speed;structural determinants;sugar;Testing;vaccine development;Viral;viral fitness;Viral Pathogenesis;Viral Proteins;viral RNA;Virion;Work

PROJECT_TITLE: RNA-dependent RNA Polymerase


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Kidney Disease;Nutrition;Obesity;Orphan Drug;Rare Diseases;Urologic Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: NARRATIVE Oxalate is a waste product produced by the liver and also present in various foods. The main route of oxalate excretion is the kidneys where it can produce calcium oxalate kidney stones for which there are currently no approved therapies. This proposal aims to advance first-in-class drug candidates (SLC26A3 inhibitors) that block oxalate uptake in the intestine and thus direct oxalate excretion through stool and protect the kidneys from the detrimental effects of oxalate.

PI_NAMEs: CIL, ONUR  (contact)

PROGRAM_OFFICER_NAME: KETCHUM, CHRISTIAN J

PROJECT_TERMS: ABCB1 gene;absorption;Acute;animal efficacy;Animal Model;Anions;bariatric surgery;Bicarbonates;Binding Proteins;Biological Availability;Biological Process;Calcium;Calcium Oxalate;Cells;Chemicals;Chemistry;Chlorides;Chronic Kidney Failure;Clinical;clinically relevant;Colon;compound 30;Cystic Fibrosis;Data;Deposition;Development;Diet;dietary;Disease Progression;Dose;drug candidate;Drug Kinetics;efficacy study;efficacy testing;Enteral;Enzymes;Excretory function;Exocrine pancreatic insufficiency;experimental study;extracellular;Feces;Food;Frequencies;G-Protein-Coupled Receptors;Gastric Bypass;Gastrointestinal Diseases;General Population;Goals;high throughput screening;Histology;Human;Hyperoxaluria;In Vitro;in vitro testing;in vivo;Industry Standard;Inflammatory Bowel Diseases;Ingestion;inhibitor;Intestines;Ion Channel;Kidney;Kidney Calculi;Kidney Diseases;Knockout Mice;lead candidate;Liver;Metabolic;Modeling;mouse model;Mus;Mutation;nanomolar;Nephrocalcinosis;Nephrolithiasis;novel;novel strategies;Obese Mice;Obesity;Oral;Oxalates;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Plasma Proteins;preclinical development;Primary Hyperoxaluria;programs;Property;Rattus;renal calcium;Research Contracts;Risk;Risk Factors;Rodent Model;Route;Safety;scaffold;screening;Serum;Site;SLC26A3 gene;small molecule;Sodium;Solubility;Surface;Testing;Therapeutic;Tissues;Toxic effect;Toxicity Tests;treatment strategy;uptake;urinary;Urinary Calculi;Urine;Waste Products

PROJECT_TITLE: SLC26A3 (DRA) Inhibitors for Treatment of Hyperoxaluria and Nephrolithiasis


ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative Diseases such as sepsis, stroke and heart attack involve a program of cell death called pyroptosis that leads to breakdown of the cell membrane, or lysis. Our data demonstrate that muscimol is a small molecule that prevents lysis during pyroptosis, but we do not yet understand how this happens. This proposal aims to understand the mechanism of muscimol protection and determine the structural requirements for protective small molecules, with the ultimate goal of defining a new paradigm for disease intervention.

PI_NAMEs: FINK, SUSAN LEILANI (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Affect;Agonist;analog;Area;Binding Proteins;CASP1 gene;Caspase;Cell Death;Cell Death Process;Cell membrane;Cells;chemical property;Coupled;Cytolysis;Data;Development;Disease;experimental study;Exposure to;Family;Foundations;Future;GABA Agonists;GABA Receptor;Glycine;Goals;human disease;Immune signaling;in vivo evaluation;Inflammasome;Inflammatory;inhibitor;innovation;Intervention;Lytic;Mediating;member;Modeling;Molecular;mortality;Muscimol;Myocardial Infarction;Nervous System Physiology;Neurons;novel;novel therapeutic intervention;Parents;Pathogenesis;Pathology;Peptide Hydrolases;Peptides;prevent;Process;programs;Property;Proteins;Proteomics;receptor;release factor;Research Project Grants;Role;Rupture;Sepsis;Shotguns;Site;small molecule;Stimulus;Stroke;Structure-Activity Relationship;System;systemic inflammatory response;Testing;Therapeutic;therapeutic target;Ultraviolet Rays;VDAC1 gene

PROJECT_TITLE: Mechanism of Muscimol as a Novel Pyroptosis Inhibitor

STUDY_SECTION: CSRS

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Assistive Technology;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Disability Research;Hearing Loss;Mental Health;Neurodegenerative;Neurosciences;Rehabilitation

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Neuropsychiatric symptoms (NPS) are major manifestations of Alzheimer’s disease and Related Dementias (ADRD) and a major public health problem. Although hearing loss has been shown to be independently associated with more severe NPS, hearing loss largely goes undetected and unaddressed among older adults with ADRD. The goal of the proposal is to refine an affordable, accessible hearing care intervention strategy from a prior study, evaluate preliminary efficacy of the revised hearing care intervention, and characterize response heterogeneity and potential underlying mechanism(s) of action between hearing care and NPS.

PI_NAMEs: NIEMAN, CARRIE L;OH, ESTHER SEUNGHEE (contact)

PROGRAM_OFFICER_NAME: RIDDLE, MELISSA

PROJECT_TERMS: Address;Admission activity;Adult;Adverse event;Age;Agitation;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Ambulatory Care;Attenuated;Behavior Therapy;Caring;Characteristics;Clinic;Clinical;cohort;Communication;Communication impairment;comorbidity;Consultations;Control Groups;cost;Dementia;dementia care;Devices;Disease;Disease Progression;Distress;efficacy trial;Elements;Ensure;Environmental Risk Factor;Equation;Equipment and supply inventories;Ethnic Origin;Etiology;experience;Exposure to;functional decline;Goals;Health;Hearing;Hearing Aids;hearing impairment;Hearing Tests;Heterogeneity;High Prevalence;holistic approach;Home;human old age (65+);Impaired cognition;implementation barriers;improved;Individual;innovation;insight;Institution;Intervention;intervention refinement;Interview;Knowledge;Link;Maintenance;Manuals;Measures;Mental Depression;Methodology;Methods;mild cognitive impairment;Modeling;Nature;neuropsychiatric symptom;neuropsychiatry;Nonpharmacologic Therapy;Nursing Homes;older adult;Outcome;Outcome Measure;Outpatients;Patients;Perception;Personal Satisfaction;Pharmaceutical Preparations;Pilot Projects;post intervention;Presbycusis;Prevalence;primary outcome;Process;Protocols documentation;Public Health;Quality of life;Questionnaires;Race;Randomized, Controlled Trials;Recommendation;recruit;reduce symptoms;Research;responders and non-responders;response;Role;Safety;Series;Severities;Sleep disturbances;socioeconomics;Specific qualifier value;Structure;Surveys;symptom management;Symptoms;Target Populations;Technology;tertiary prevention;Testing;theories;Therapeutic;therapy design;Time;Translating;Waiting Lists;Work

PROJECT_TITLE: Addressing Hearing Loss as a Common Unmet Contributor to Neuropsychiatric Symptoms


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Clinical Research;Hematology;Immunotherapy;Pediatric;Pediatric Cancer;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

PHR: PROJECT NARRATIVE Allogeneic hematopoietic stem cell transplantation (SCT) is a curative therapy for high-risk acute myeloid leukemia (AML); however, SCT suffers from substantial treatment related toxicity and a high frequency of disease relapse. It is likely that AML is cured post-SCT due to donor immune cells targeting minor histocompatibility antigens (mHA) presented by patient leukemia cells. This research proposal will investigate the magnitude of donor immune targeting of leukemia associated mHA and mechanisms of resistance active in AML, which could lead to improved SCT outcomes.

PI_NAMEs: VINCENT, BENJAMIN G (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Allogenic;Antigen Presentation;Antigen Targeting;antigen-specific T cells;Automobile Driving;Behavior Therapy;Biochemical;Biological Assay;Cause of Death;CD8-Positive T-Lymphocytes;Cell-Mediated Cytolysis;Cells;Clinical;Clinical Protocols;computational pipelines;computerized tools;curative treatments;cytotoxicity;Data;Data Set;disorder risk;donor stem cell;empowerment;Exposure to;Failure;Frequencies;Gene Expression Profiling;genetic variant;Goals;graft vs host disease;graft vs leukemia effect;Hematopoietic;Hematopoietic Stem Cell Transplantation;hematopoietic tissue;high risk;Human;human tissue;Immune;Immune Targeting;immunogenicity;Immunologics;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;Investigation;leukemia;leukemia relapse;Leukemic Cell;Major Histocompatibility Complex;Maps;Mass Spectrum Analysis;Measurement;Measures;Mediating;Methods;Minor Histocompatibility Antigens;Mutation;neoantigens;novel;Outcome;Patients;Phenotype;Population;Predisposition;pressure;prevent;Prevention;Proliferating;Protocols documentation;Recurrent disease;Relapse;Research;Research Proposals;Resistance;resistance mechanism;response;Role;Sampling;single-cell RNA sequencing;Specificity;Statistical Models;Stem cell transplant;T cell response;T-Lymphocyte;Technology;Testing;Time;Tissue Banks;transcriptome;Transplant Recipients;Treatment-related toxicity;tumor;Work

PROJECT_TITLE: Gvl mHA Specific T Cell Responses Prevent AML Relapse Following Allogeneic Stem Cell Transplantation

STUDY_SECTION: TTT

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


NIH_SPENDING_CATS: Infectious Diseases

ORG_DEPT: BIOCHEMISTRY

PHR: Fungal cells have a family of surface-attached proteins that aggregate to enable cell-cell interactions and virulence through properties shared with disease-causing proteins that aggregate in neurodegenerative disorders. We hypothesize that the specificity of fungal interactions through these aggregation-prone sequences drives cell-cell recognition in microbial communities, and here we will determine cross-protein interactions with these sequences. The data will identify barriers to this type of protein aggregation and advance our understanding of targets for antifungal drug development.

PI_NAMEs: GESTWICKI, JASON E;KUMAR, ANUJ  (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Adhesions;Affect;Amino Acids;Amyloid;Amyloid Fibrils;Amyloid Proteins;amyloid structure;anti-fungal agents;Antifungal Therapy;Bacterial Adhesins;Binding;Biological Assay;Biology;Candida albicans;Cell Adhesion;Cell Communication;Cell surface;cell type;Cell Wall;Cell-Cell Adhesion;Cells;Communities;Data;Development;Discrimination;Disease;drug development;Exclusion;experience;experimental study;Family;fascinate;Filament;Flocculation;functional genomics;fungus;Future;Genetic study;genome-wide;glycosylation;Goals;Growth;high throughput screening;Human;improved;Infection;innovation;insight;Investigation;Knowledge;knowledgebase;Link;Mediating;Methods;microbial;Microbial Biofilms;microbial community;Molecular;Mus;nano;Neurodegenerative Disorders;novel;Outcome;Pathogenesis;pathogenic fungus;Phenotype;Pilot Projects;Point Mutation;Prions;Process;Property;protein aggregation;Protein Isoforms;Proteins;Rapid screening;Recombinant Proteins;remediation;Role;Saccharomyces cerevisiae;scaffold;screening;self assembly;Specificity;structural determinants;Structure;Supporting Cell;Surface;System;Tandem Repeat Sequences;tau Proteins;Testing;Variant;Virulence;Virulence Factors;Work;Yeasts

PROJECT_TITLE: Adhesin Amyloid Biology

STUDY_SECTION: MSFB

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


NIH_SPENDING_CATS: Autoimmune Disease;Biomedical Imaging;Brain Disorders;Clinical Research;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: AMHERST

ORG_DEPT: NEUROLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it will open new horizons for the development of more efficacious treatments of multiple sclerosis by providing a deeper understanding of the mechanisms driving disease progression. The project is relevant to NINDS’s mission because it paves the way for therapeutic discoveries to reduce the burden of multiple sclerosis by generating fundamental knowledge about the association between cellular iron loss in the gray matter and different aspects of disease progression.

PI_NAMEs: SCHWESER, FERDINAND  (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: acute symptom;Affect;Atrophic;Automobile Driving;Biochemical Pathway;Biological;Biological Markers;Brain;Brain Injuries;brain iron;Cell Nucleus;Chronic Phase of Disease;Clinical;clinical application;clinical practice;clinical predictors;Clinical Trials;cofactor;comparison control;Data;deprivation;Detection;Development;disability;Disease;Disease Progression;Disease remission;disorder subtype;effective therapy;efficacious treatment;Evolution;Finding by Cause;Functional disorder;Giant Cells;Goals;gray matter;Homeostasis;illness length;Image;imaging biomarker;improved;in vivo;individual patient;inflammatory modulation;Injury;innovation;Iron;Knowledge;Lesion;Link;Longitudinal Studies;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Magnetism;Maps;Measurement;Measures;Mission;model generalizability;Modeling;Molecular;Monitor;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;Myelin;National Institute of Neurological Disorders and Stroke;Nerve Degeneration;Neuroglia;Neuronal Injury;novel;novel therapeutic intervention;Oligodendroglia;Outcome;Outcome Measure;Pathogenicity;Pathologic;Pathology;Patients;Physiological;Predisposition;Process;Public Health;Pulvinar structure;Research;Role;Signal Transduction;Symptoms;Techniques;Thalamic structure;Therapeutic;Time;Tissues;Toxic effect;white matter

PROJECT_TITLE: Deep Gray Matter Iron and Disease Progression in Multiple Sclerosis

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Neurosciences

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Ingestion of food contaminated by Listeria monocytogenes bacteria causes two different types of brain infection in humans. One type (meningitis) happens primarily in individuals with compromised immune systems (for example, neonates and the elderly); the other type (rhombencephalitis) occurs in otherwise healthy people. The goal of this research is to identify the bacterial factors which allow Listeria to invade cranial nerves in the gut and spread directly to the brainstem resulting in rhombencephalitis.

PI_NAMEs: D'ORAZIO, SARAH E. F. (contact)

PROJECT_TERMS: Actins;Alleles;Animal Model;Area;Axon;Bacteremia;Bacteria;Bacterial Adhesins;Blood;Blood - brain barrier anatomy;blood-brain barrier crossing;Body System;Brain;Brain Stem;Bypass;Cattle;Cell Nucleus;cell type;Cells;Clinical;Coculture Techniques;Cranial Nerves;Data;Death Rate;Diffuse;Elderly;Endowment;Enteral;enteric infection;Enteric Nervous System;Event;Failure;Follow-Up Studies;Food Contamination;foodborne;foodborne illness;foodborne infection;Goals;Growth;Gut Mucosa;Human;Immune;Immune system;Immunocompetent;In Vitro;in vivo;Individual;Infection;Inflammatory;Inflammatory Response;Ingestion;insight;intestinal epithelium;Intestines;Intravenous;Invaded;Kinetics;Lamina Propria;Length;Life;Listeria;Listeria monocytogenes;Listeriosis;live cell imaging;Liver;Lymphoid;Mediating;Membrane Proteins;Meningitis;Meningoencephalitis;microbiome;microbiota;Microscopic;migration;Monitor;Motility;mouse model;Movement;Mus;Mutagenesis;mutant;Myelogenous;Myenteric Plexus;Nature;neonate;Nerve;nerve supply;Nervous System;neural;Neuroglia;Neurons;neurotropic;Neurotropism;neurovirulence;novel;Oral;pathogen;Pathogenesis;Pattern;Persons;Phase;Process;Proline-Rich Domain;Proteins;Reporting;Research;Role;Route;Sheep;Slice;Speed;Spleen;Submucosa;Submucous Plexus;System;Tail;Testing;Time;Tissues;transmission process;Vagus nerve structure;Variant;Virulence Factors;Work

PROJECT_TITLE: Invasion of the enteric nervous system by neurotropic Listeria monocytogenes

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Narrative: We must understand how a mutation causes cancer before we can develop targeted therapeutics or design drug combinations that eliminate the leukemic cells, leaving normal cells to flourish. This proposal seeks to define how AML1-ETO alters epigenetic circuits to establish a permissive environment that allows secondary mutations to transform these cells into AML. We will focus on the recruitment of HDAC3 and PRC1.5 by AML1-ETO and test how recruitment of these histone-modifying complexes is use to set the stage for the development of AML.

PI_NAMEs: HIEBERT, SCOTT W (contact)

PROJECT_TERMS: Abbreviations;Acute Myelocytic Leukemia;Affect;Affinity Chromatography;Alleles;AML1-ETO fusion protein;analog;Binding;Biological Assay;Cancer Etiology;CBFA2T1 gene;CD34 gene;CEBPA gene;Cell Culture Techniques;Cell Differentiation process;Cell fusion;Cell Nucleus;cell transformation;Cells;chemical genetics;chemotherapy;Chimeric Proteins;ChIP-seq;Chromatin;Chromosomal translocation;Cleavage Under Targets and Release Using Nuclease;Cloning;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Compensation;Complex;Coupled;Coupling;CRISPR/Cas technology;Cytoplasm;Data;Development;differential expression;DNA Binding Domain;DNA-Directed RNA Polymerase;DRPLA protein;Drug Combinations;Drug Design;Enhancers;Environment;Enzymes;Epigenetic Process;established cell line;Family member;Future;Gene Expression;Genes;Genetic;Genetic Complementation Test;Genetic Transcription;Genome;Genomics;GFI1B gene;Goals;HDAC3 gene;Hematopoietic;Hematopoietic stem cells;histone modification;Histones;Human;Impairment;inhibitor;insight;Intestinal Neoplasms;KAI1 gene;Leukemic Cell;leukemogenesis;Link;Mass Spectrum Analysis;Mediating;Methods;Methylation;Modeling;Molecular;mouse genetics;mouse model;Mutate;Mutation;Myelogenous;Normal Cell;novel;Nuclear;Nucleosomes;Outcome;Patients;permissiveness;Phenotype;Point Mutation;PRC1 Protein;Preleukemia;Prognostic Marker;programs;Protac;protein degradation;Proteins;Reagent;recruit;Regulator Genes;Relapse;Repression;RNA Interference;Role;Running;RUNX1 gene;side effect;small hairpin RNA;Sodium Chloride;Solid Neoplasm;success;System;t(8;21) acute myeloid leukemia;t(8;21)(q22;q22);targeted treatment;Testing;Thalidomide;Time;tool;Transcript;transcription factor;Transcriptional Regulation;transcriptome sequencing;Tumor Suppressor Proteins;tumorigenesis;ubiquitin isopeptidase;ubiquitin-protein ligase;Work;yeast two hybrid system;Yeasts

PROJECT_TITLE: Role of PRC1 in RUNX1-ETO-mediated transcriptional control

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Kidney Disease;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Embryonic - Non-Human;Transplantation

ORG_CITY: NEW YORK

ORG_NAME: ROGOSIN INSTITUTE

PHR: Approximately 730,000 Americans have end stage renal disease, in which kidney function is insufficient to sustain life. Ex vivo organogenesis has the potential both to provide functional tissue for renal replacement therapy and to provide research tools with which we can understand the causes of chronic kidney disease and identify new therapies. The long-term goal of this proposal is to establish protocols that will enable the generation of functionally significant numbers of physiologically relevant, vascularized nephrons in culture and in grafted tissues and the technology to asses function.

PI_NAMEs: CARROLL, THOMAS JOSEPH;CLEAVER, ONDINE B;MARCIANO, DENISE K;OXBURGH, LEIF  (contact);YODER, BRADLEY K.

PROGRAM_OFFICER_NAME: BRUNSKILL, ERIC WAYNE

PROJECT_TERMS: American;Anastomosis - action;Anatomy;Animals;Biological Assay;Blood Vessels;Cardiovascular system;Cell Line;Cellular biology;Chronic Kidney Failure;Complement;Complex;Cues;Data;Embryo;End stage renal failure;Engraftment;Enzyme-Linked Immunosorbent Assay;Epithelium;fluid flow;Generations;Goals;graft function;Growth;human induced pluripotent stem cells;Image;Imaging technology;Impairment;Implant;in vivo;in vivo evaluation;induced pluripotent stem cell;Investigation;Kidney;Kidney Diseases;Kidney Transplantation;Knowledge;Laboratories;Left;Life;Macrophage;Maintenance;Mus;nephrogenesis;Nephrons;Normal Statistical Distribution;novel;novel therapeutics;Organogenesis;Organoids;Patients;Pattern;Physiological;Population;Production;Protocols documentation;Reagent;recruit;regenerative;renal epithelium;Renal function;Renal Replacement Therapy;Renal Tissue;replacement tissue;Reporter;Research;Resources;Role;Series;Signal Pathway;Signal Transduction;Site;Source;stem cell niche;Stromal Cells;Techniques;Technology;Testing;Tissue Grafts;Tissues;tool;Tubular formation;Urinary system;Urine;Vascular System;Vascularization

PROJECT_TITLE: Application of Progenitor Niche Signals to Ex Vivo Nephrogenesis


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Clinical Research;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Orphan Drug;Pediatric;Precision Medicine;Rare Diseases;Rett Syndrome;Women's Health Research

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project narrative MECP2 Duplication Syndrome (MDS) and Rett Syndrome (RTT) are allelic diseases, caused, respectively, by too much and too little MeCP2. MDS is now poised for clinical trials of disease-altering treatments such as anti-sense oligonucleotides (ASO), yet we lack reliable biomarkers to prevent over-suppression of MeCP2 (which would produce Rett symptoms). We have identified several molecules that track with MeCP2 levels in both mice and human MDS subjects, and will validate these biomarkers and our clinical measures in the largest cohort of MDS subjects collected to date.

PI_NAMEs: PEHLIVAN, DAVUT  (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Affect;Alleles;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;Automobile Driving;Biliverdine;Binding Proteins;Biological Markers;biomarker identification;biomarker panel;biomarker validation;Blood specimen;Boston;Brain;Brain region;candidate marker;Cell Nucleus;Child;Chromatin;Clinical;clinical biomarkers;clinical diagnostics;clinical outcome measures;Clinical Trials;cohort;comparative genomic hybridization;Complex;Country;debilitating symptom;Dedications;Development;diagnostic criteria;Disease;DNA Sequence Rearrangement;Dose;Drops;Enrollment;Female;gene product;Genes;Genetic;genome sequencing;Genomics;Genotype;Heme;Human;human subject;humanized mouse;Intellectual functioning disability;Link;loss of function mutation;lymphoblast;male;Maps;Measurable;Measurement;Measures;MeCP2 Duplication Syndrome;Mentors;Methyl-CpG-Binding Protein 2;Modality;molecular marker;Moods;motor control;multiple omics;Mus;Natural History;Neurodevelopmental Disorder;Neurons;Nuclear;Office Visits;Optics;Outcome Measure;patient population;Patients;Pediatric Hospitals;Phenotype;Phosphoric Monoester Hydrolases;Phosphotransferases;Physical Examination;Population;Positioning Attribute;preclinical study;prevent;Proteins;Recording of previous events;Resolution;Rett Syndrome;Severities;Severity of illness;Structure;Symptoms;Syndrome;Texas;Therapeutic;treatment response;Universities;Visit;Western Blotting;whole genome;Wild Type Mouse;Work

PROJECT_TITLE: Comprehensive Deep Phenotyping and Multi-omics to Develop Clinical and Molecular Biomarkers for MeCP2-related Diseases

STUDY_SECTION: NST

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


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: The goal of this proposal is the development of aqueous scandium and lutetium coordination chemistry that enables the synthesis of 18F, 43/44/47Sc and 177Lu labeled radiopharmaceuticals under mild conditions compatible with biologics. The corresponding constructs will be validated using comprehensive chemical, in vitro and in vivo analyses.

PI_NAMEs: BOROS, ESZTER  (contact)

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: Acceleration;Albumins;Amides;Antigen Targeting;aqueous;Binding;Biological Products;Chelating Agents;chelation;Chemicals;Chemistry;chemotherapy;Clinical;clinical application;clinical development;cohort;cold temperature;Companions;Complex;Development;Diagnostic;Disadvantaged;Discipline of Nuclear Medicine;Disease;Dose;dosimetry;Drug Kinetics;Fluorine;FOLH1 gene;Generations;Goals;Half-Life;Hardness;Image;improved;In Vitro;in vivo;in vivo evaluation;Injections;Ions;Isotope Therapy;Isotopes;Kinetics;Knowledge;Label;Libraries;Link;Lutetium;metallicity;Metals;Methods;Mus;Nitrogen Dioxide;novel;Patient-Focused Outcomes;Peptides;Performance;Plant Resins;Positron-Emission Tomography;pre-clinical;Procedures;Production;Property;Proteins;Radial;Radiation therapy;radiochemical;Radiochemistry;Radioisotopes;Radiolabeled;Radiopharmaceuticals;rational design;Saline;Scandium;small molecule;Solid;System;targeted imaging;Temperature;theranostics;Therapeutic;Tracer;tumor;tumor growth;Validation;Xenograft Model

PROJECT_TITLE: Harnessing scandium chelation chemistry for the development of radiopharmaceuticals

STUDY_SECTION: SBCA

STUDY_SECTION_NAME: Synthetic and Biological Chemistry A Study Section[SBCA]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);American Indian or Alaska Native;Atherosclerosis;Behavioral and Social Science;Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Dementia;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Heart Disease - Coronary Heart Disease;Infectious Diseases;Neurodegenerative;Neurosciences;Nutrition;Obesity;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: ORANGE

ORG_NAME: CHAPMAN UNIVERSITY

PHR: This research will investigate the risk of cognitive impairment, dementia and brain atrophy in relation to physical activity, infection and immune pathways, biological sex, and APOE genotype among two cohorts of Native Americans whose lifestyle and environment require high levels of physical activity and expose them to high pathogen burdens, most like the human preindustrial past. The study extends on-going research that has revealed a very low prevalence of dementia, especially Alzheimer’s disease, but a high level of arterial calcification in the brain associated with mild cognitive impairment. These populations offer a vanishing opportunity to study how risk factors operate in diverse environments, assess the role of infection in AD and brain aging, and generate a biobank for future research and access to data-sharing consortia.

PI_NAMEs: FINCH, CALEB E;GATZ, MARGARET ;GURVEN, MICHAEL DOUGLAS;KAPLAN, HILLARD S (contact);STIEGLITZ, JONATHAN P;THOMAS, GREGORY SCOTT;THOMPSON, RANDALL ;TRUMBLE, BENJAMIN CHAPIN

PROGRAM_OFFICER_NAME: ANDERSON, DALLAS

PROJECT_TERMS: 2019-nCoV;Adult;Affect;Age;aged;aging brain;Alleles;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;amyloid peptide;Anti-Inflammatory Agents;Antibodies;Antigens;Aorta;Apolipoprotein E;Apolipoproteins;Arteriosclerosis;Atherosclerosis;Atrophic;Bacterial Antigens;Bacterial Infections;Basal Ganglia;biobank;Biological;Biological Markers;biological sex;Blood;Blood - brain barrier anatomy;blood lipid;Brain;Brain region;brain volume;calcification;Carotid Arteries;case control;causal model;cerebral atrophy;Chest;Cognition;Cognitive;cognitive testing;cohort;Collection;Coronary Arteriosclerosis;Coronary artery;Data;Data Collection;Dementia;dementia risk;design;Developing Countries;Diet;differential expression;Disease;Disease Outcome;Environment;Europe;European;Exposure to;Family;Fatty acid glycerol esters;Female;Food;Gene Expression;Gene Expression Profile;gene network;Genes;Genotype;genotypic sex;gray matter;helminth infection;Helminths;Hematological Disease;High Prevalence;high risk;Human;Immune;Immune response;immunoregulation;Impaired cognition;In Vitro;Incidence;Individual;Industrialization;Infection;Inflammasome;Inflammation;Inflammatory Response;innovation;Interview;Intestinal parasite;Intestines;Leadership;Leukocyte Trafficking;Life Style;Link;Longitudinal Studies;Low Prevalence;male;Measures;Medial;Mediator;Medical;Messenger RNA;Metabolic;mild cognitive impairment;Native American population;Native Americans;neurofilament protein L;Neurologic;Neuropathy;Obesity;Parasites;Parasitic infection;pathogen;Pathogenesis;Pathway interactions;Physical activity;Play;Population;population based;Population Study;post-COVID-19;Prevalence;Production;Research;Risk;Risk Factors;Risk Reduction;Role;Sampling;Scanning;screening;Severities;sex;Sex Differences;Signal Transduction;South American;Specimen;tau Proteins;Testing;transcriptome;transcriptomics;Variant;Vascular Endothelial Growth Factors;Viral;Viral Antigens;Virus Diseases;white matter;Whole Blood;X-Ray Computed Tomography

PROJECT_TITLE: Testing Hypothesized Pathways Linking Infection, Physical Activity, Apoe Genotype, And Biological Sex To Low Dementia Prevalence And Reduced Brain Atrophy In Two Native American Populations

STUDY_SECTION: NAME

STUDY_SECTION_NAME: Neurological, Aging and Musculoskeletal Epidemiology Study Section[NAME]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Natural Products;Neurosciences;Orphan Drug;Rare Diseases

ORG_DEPT: NEUROSURGERY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: NARRATIVE The blood-brain barrier (BBB) is major obstacle to medical therapy of infiltrative glioma. Here we test an approach that allows for repeated and reversible BBB disruption, thus allowing systemic agents to penetrate the brain and tumor tissue in high concentrations. Our clinical trial will directly investigate the efficacy of this approach for delivery of paclitaxel, one of the most potent chemotherapeutics for this disease, and test the ability of this technology to actually increase the concentration of drugs in the human brain, a key question for drug delivery for brain cancer.

PI_NAMEs: SONABEND, ADAM M (contact);STUPP, ROGER

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Abraxane;Albumins;Area;Binding;Biopsy;Blood - brain barrier anatomy;blood-brain barrier crossing;blood-brain barrier disruption;blood-brain barrier penetration;bone;Brain;Brain Injuries;Brain Neoplasms;Brain region;brain tissue;brain volume;Bypass;Carboplatin;Cell Line;Cells;chemotherapy;Clinical;Clinical Research;Clinical Trials;cohort;comparative efficacy;contrast enhanced;Controlled Clinical Trials;cranium;Cremophor;design;Devices;Disease;disorder control;Dose;Drug Delivery Systems;efficacy evaluation;Excision;Exhibits;Exposure to;Failure;FDA approved;first-in-human;Formulation;Generations;Glioblastoma;Glioma;glioma cell line;Human;human study;Implant;implantable device;implantation;improved;improved outcome;Infiltration;Infusion procedures;intravenous injection;Localized Disease;Location;Magnetic Resonance Imaging;Malignant neoplasm of brain;Maps;Maximum Tolerated Dose;Measures;Mediating;Medical;Microbubbles;Microtubules;neurotoxicity;novel;novel therapeutic intervention;Operative Surgical Procedures;Paclitaxel;Patients;Pattern;Penetration;Perfusion;Peripheral Nerves;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phase I Clinical Trials;Phase I/II Trial;Physiologic pulse;Plasma;Postoperative Period;Pre-Clinical Model;prevent;primary endpoint;Primates;Procedures;Progression-Free Survivals;prototype;Radiation therapy;radiological imaging;Recommendation;Recurrence;Residual Neoplasm;Role;Safety;safety testing;Sampling;Solid Neoplasm;Solvents;Sonication;Source;Surgical margins;Survival Rate;Technology;temozolomide;Testing;Therapeutic;Thick;Tissues;Toxic effect;Treatment Protocols;tumor;tumor growth;Tumor Tissue;Ultrasonic wave;ultrasound;uptake;Work

PROJECT_TITLE: Blood-brain barrier disruption with implantable ultrasound to enhance paclitaxel delivery: A Phase 1-2 clinical trial in recurrent glioblastoma


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

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE Adult stem cell function is defined by multipotency, self-renewal, and plasticity, and is required for homeostasis and regeneration in epithelial tissues. This project aims to understand how stem cell function is genetically regulated by dynamic chromatin landscapes, including how cells can be “primed” to adopt alternative cell fates via differentiation and de-differentiation. By applying in vivo and in vitro tools to study chromatin regulation in stem cells of the intestinal epithelium, this project will address basic questions at the interface of genomics and cell biology with foundational relevance to human health and disease, including inflammation, traumatic injury/regeneration, and cancer.

PI_NAMEs: GRACZ, ADAM DAVID (contact)

PROJECT_TERMS: Adopted;Adult;adult stem cell;Aging;Biological Models;Cell Differentiation process;cell type;Cells;Cellular biology;Chromatin;chromatin modification;Dedications;Development;Disease;Enhancers;Enzyme Interaction;Enzymes;epithelial stem cell;Epithelium;Equilibrium;Exhibits;genomic locus;Genomics;Goals;Health;Homeostasis;Human;In Vitro;in vivo;Infection;Inflammation;Informal Social Control;Injury;interest;intestinal epithelium;Intestines;Life;Malignant Neoplasms;Modeling;mouse model;Natural regeneration;novel;progenitor;programs;Property;regeneration following injury;Regenerative response;Regulation;Reporter;Research;response;self-renewal;Site;stem cell differentiation;stem cell function;stem cells;stemness;Tissues;tool;transcription factor;Transgenes;Traumatic injury;tumorigenesis

PROJECT_TITLE: Chromatin regulation of epithelial stem cell function

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


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT RELEVANCE The formation of an organism during development requires cells to actively proliferate and to subsequently differentiate or enter proliferation pause. The proposed research aims to understand how the pathways that promote cell proliferation are regulated by and intersect with developmental and nutritional signals to promote accurate tissue formation. Understanding this regulation will be critical to elucidating the origin of cancer, where cells proliferate uncontrollably, as well as certain developmental abnormalities where cell proliferation is halted.

PI_NAMEs: LARA-GONZALEZ, PABLO ANDRES (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Abnormal Cell;Address;aging related;Biochemistry;Caenorhabditis elegans;Cancer Etiology;Cell Cycle;Cell Cycle Regulation;Cell Cycle Stage;Cell Differentiation process;cell fate specification;Cell Proliferation;Cells;Complex;Cues;Cyclin B;Defect;Development;Disease;Embryonic Development;Equilibrium;Event;Failure;Generations;Genomics;Germ Lines;Goals;In Vitro;in vivo;insight;Malignant Neoplasms;Mitosis;Mitotic;Molecular;Nutrient;Nutritional;Organism;Pathway interactions;prevent;programs;Proliferating;Regulation;Research;response;Signal Transduction;Tissues;Work

PROJECT_TITLE: Developmental regulation of the cell cycle machinery

STUDY_SECTION: MRAC

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


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Normal vision requires photoreceptors to transmit their light-generated signals to other neurons in the retina and loss in this ability results in many blinding conditions. The work proposed herein will yield a clearer understanding of the structural organization of molecular complexes at photoreceptor synapses which is expected to increase our understanding of blinding retina diseases and facilitate the development of therapies for them.

PI_NAMEs: MARTEMYANOV, KIRILL A. (contact);SINGH, APPU

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: Architecture;Biochemical;Biochemistry;Bipolar Neuron;Blindness;Brain;Cell Adhesion;Cell Adhesion Molecules;Cells;Cellular biology;Cessation of life;Collaborations;Communication;comorbidity;Complex;Cone;Cone dystrophy;Cryoelectron Microscopy;Dedications;Disease;Elements;experimental study;extracellular;follow-up;Functional disorder;G-Protein-Coupled Receptors;Glean;Glutamates;Goals;GTP-Binding Protein Regulators;Human;improved;India;interdisciplinary approach;International;Laboratories;Light;macromolecular assembly;Membrane Potentials;Molecular;Molecular Structure;Mutation;Neurons;Neurotransmitter Receptor;Neurotransmitters;Night Blindness;novel therapeutic intervention;Ocular Pathology;Orphan;Photons;Photoreceptors;Phototransduction;Play;postsynaptic;presynaptic;Presynaptic Terminals;programs;protein protein interaction;Proteins;receptor;reconstitution;Regulation;Research;Resolution;response;Retina;Retinal Cone;Retinal Diseases;RGS Proteins;Rod;Role;scaffold;Sensory;Signal Transduction;Site-Directed Mutagenesis;Structure;success;Synapses;Synaptic Cleft;synaptic function;Synaptic Receptors;Synaptic Transmission;System;therapy development;transmission process;Vertebrate Photoreceptors;virtual;Vision;visual processing;Work

PROJECT_TITLE: Structural landscape of photoreceptor synapses

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Precision Medicine

ORG_DEPT: PHYSIOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative Drug repositioning - the application of approved drugs in a novel disease context - has gained increasing attention as a way to identify alternative treatment strategies for Alzheimer's Disease (AD). We here propose a novel machine-learning approach to identify drug repositioning candidates in a network-based framework by combining multi-omics associations from large studies of AD with molecular pathway information, extensive drug-drug target data, as well as molecular drug effect data. In silico repositioning candidates will be further prioritized through retrospective analyses in studies of AD and large-scale mining of electronic health records, and the resulting top three candidates will be experimentally validated in mouse models of AD.

PI_NAMEs: ARNOLD, MATTHIAS ;KRUMSIEK, JAN  (contact)

PROGRAM_OFFICER_NAME: ARUNKUMAR, NANDINI

PROJECT_TERMS: Acceleration;Address;Affect;Age;Aging;aging population;Algorithms;alternative treatment;Alzheimer's Disease;Alzheimer's disease model;amyloid pathology;Animal Model;Atlases;Attention;Attenuated;Autopsy;Behavior assessment;Behavioral;Binding;biobank;Biological Markers;biological systems;Biomedical Research;Brain;candidate identification;candidate selection;Clinical;Clinical Trials;Cognitive;Collection;Complex;Data;data mining;Data Set;Databases;Development;Disease;drug candidate;Drug Combinations;drug development;Drug Exposure;drug repurposing;Drug Screening;Drug Targeting;Drug usage;Electronic Health Record;Electrophysiology (science);endophenotype;Exhibits;experimental study;Future;Gene Expression Regulation;genetic association;Genetic Complementation Test;genome wide association study;Graph;graph database;Immunohistochemistry;in silico;Individual;Intake;Intervention;Investments;Late Onset Alzheimer Disease;Link;Longitudinal Studies;Machine Learning;machine learning method;Measures;Medicine;Memory;Metabolic Pathway;metabolomics;Methods;Mining;Molecular;Molecular Profiling;mouse model;multidisciplinary;multiple omics;Network-based;Neurodegenerative Disorders;neuroimaging;neuropathology;novel;old mice;Outcome;Pathology;Pathway Analysis;Pathway interactions;Pharmaceutical Preparations;Pharmacogenomics;Pharmacologic Substance;Pharmacotherapy;Phase;population based;Population Study;Positioning Attribute;pre-clinical;Probability;Process;protein expression;protein protein interaction;Proteins;Publishing;Quantitative Trait Loci;Reaction;religious order study;Research;Resources;Retrospective Studies;Route;Scoring Method;Screening Result;standardize measure;Synapses;synaptic function;System;tau Proteins;Testing;Tissue-Specific Gene Expression;Tissues;treatment strategy;United States National Institutes of Health;Validation;validation studies;Visit

PROJECT_TITLE: TargetAD: A systems multi-omics approach to drug repositioning in Alzheimer's disease


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Dental, Oral, and Craniofacial Disease

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

PHR: PROJECT NARRATIVE Our nation is faced with a growing shortage of highly qualified, well-trained clinician scientists and scientists to address the expanding dental, oral and craniofacial health needs of our diverse population. The Dental Academic Research Training (DART) Program is a comprehensive research-training program focused on an innovative, integrated, multi-disciplinary approach to produce a cadre of well-trained, skilled, collaborative scientists and clinician scientists that are capable to address the critical dental, oral and craniofacial research issues of our nation. The program is housed in the University of Alabama at Birmingham School of Dentistry, ranked among the top ten in NIDCR funding (dental school and institution), which is an integral component of a vital major health science center with a “Highest Research Activity” Carnegie Classification located in the southeast region of our nation.

PI_NAMEs: JAVED, AMJAD  (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: Address;Alabama;Basic Science;Biocompatible Materials;Biomimetics;career;Classification;Clinical;Clinical Research;craniofacial;Dental;Dental caries;Dental General Practice;Dentists;design;Development;Development Plans;Developmental Biology;Doctor of Philosophy;Environment;experience;Funding;Genetic;graduate student;Grant;Health Professional;Health Sciences;Immunology;implementation science;innovation;interdisciplinary approach;Interdisciplinary Study;Knowledge;Leadership;Malignant Neoplasms;Microbiology;National Institute of Dental and Craniofacial Research;next generation;Oral;Oral health;orofacial;Outcomes Research;Pathway interactions;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;practice-based research network;pre-doctoral;Productivity;professional students;Research;Research Activity;Research Training;responsible research conduct;School Dentistry;Science;Scientist;skill acquisition;skills;Students;Training;Training Programs;Translational Research;Universities;Writing

PROJECT_TITLE: Dental Academic Research Training Program (DART)


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Behavioral and Social Science;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CHICAGO

PHR: PROJECT NARRATIVE  South Asian Americans are disproportionately burdened by atherosclerotic cardiovascular disease (ASCVD) at younger ages compared to other groups. 2nd generation South Asian Americans are hypothesized to have unique cardiovascular health profiles and risk factors compared to 1st generation immigrant South Asians. Characterizing and contextualizing antecedent cardiovascular health and its multi-level contributors in 2nd generation young South Asian American adults will provide fundamental new knowledge to adapt clinical and behavior modification prevention strategies to improve cardiovascular health trajectories and to reduce ASCVD disparities in this risk-enhanced yet understudied population.

PI_NAMEs: SHAH, NILAY S. (contact)

PROGRAM_OFFICER_NAME: COADY, SEAN

PROJECT_TERMS: 21 year old;Acculturation;Address;Adult;Adult Children;Age;American Heart Association;Ancillary Study;Asian Americans;Asian population;Atherosclerosis;Bangladesh;Behavior Therapy;behavioral health intervention;Bhutan;Body Composition;Body mass index;Calcium;Cardiology;cardiometabolic risk;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;Cardiovascular Models;Cardiovascular system;career development;Child;Clinical;Clinical Sciences;cohort;Collaborations;Communities;community engaged research;community engagement;coronary artery calcium;Death Rate;Development;Development Plans;Diabetes Mellitus;disease disparity;enhancing factor;Epidemiology;ethnic diversity;Ethnic Origin;Ethnic Population;Event;evidence base;experience;Fatality rate;feasibility trial;Funding;Future;Generations;genome sciences;genome wide association study;Genomic approach;Genomics;Guidelines;Health;Health behavior;health difference;health disparity populations;Health Promotion;Health Sciences;heart disease prevention;High Prevalence;high risk population;Hypertension;Immigrant;implementation science;improved;India;Individual;Infrastructure;Institution;Intervention;intervention mapping;Intervention Trial;Interview;Investigation;K-Series Research Career Programs;Knowledge;Life;Life course epidemiology;Life Cycle Stages;Logic;Maldives;Measures;Mediator;Medicine;Mentors;Mentorship;Minority Groups;Mission;multidisciplinary;Myocardial Infarction;National Heart, Lung, and Blood Institute;Neighborhood Health Center;Neighborhoods;Nepal;novel;Obesity;offspring;Pakistan;Parents;Participant;Patient Recruitments;Persons;Pilot Projects;polygenic risk score;Population;Population Heterogeneity;Population Intervention;Positioning Attribute;premature;Prevalence;prevent;Prevention;Prevention strategy;preventive intervention;Preventive Medicine;Primary Prevention;protective factors;Protocols documentation;racial population;recruit;Research;research and development;Research Infrastructure;Research Personnel;Risk;Risk Assessment;Risk Factors;skills;social culture;Social Network;socioeconomics;South Asian;Sri Lanka;Statistical Methods;Statistical Models;Structure;Testing;tool;Training;training opportunity;Translational Research;Universities;young adult

PROJECT_TITLE: MASALA-2G: Multi-level Assessment of the South Asian Life-course of Atherosclerosis (2nd Generation Offspring Study)

STUDY_SECTION: MPOR

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


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Combatting infectious diseases remains a centrally important quest for global health. Sustaining this mission requires a workforce of basic researchers and clinical practitioners who understand principles of how microbes cause disease, how our immune system controls infectious agents, and how beneficial microbes limit disease, all with an eye toward developing new ways of preventing or treating infectious diseases. This program provides advanced training and professional development opportunities to prepare talented Predoctoral and Postdoctoral trainees for careers dedicated to fighting infectious diseases.

PI_NAMEs: CARRUTHERS, VERNON BRUCE (contact)

PROGRAM_OFFICER_NAME: BROWN, LILIANA L

PROJECT_TITLE: Molecular Mechanisms of Microbial Pathogenesis Training Program

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE Epilepsy is the fourth most common neurological disorder, is notoriously pharmacoresistant, and is associated with cerebellar functional and structural changes that can predict negative patient outcomes. Here, I examine how the cerebellum is modulated by chronic, spontaneous hippocampal and neocortical seizures. This proposal provides key insights into alterations in cerebellar dynamics caused by spontaneous seizures and chronic epilepsy, and has the potential to identify new targets for therapeutic modulation across different seizure foci.

PI_NAMEs: STRENG, MARTHA L (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Acute;Address;Affect;Anatomy;Area;Attenuated;attenuation;Behavior;Behavioral;Calcium;career;Cell Nucleus;Cerebellar Cortex;Cerebellum;Cerebral cortex;Cessation of life;Chronic;Cognitive deficits;comorbidity;Cues;Data;Disease;Dorsal;Electrophysiology (science);Epilepsy;epileptiform;experience;Foundations;Functional disorder;Goals;Grant;Health;Hippocampus;Image;Impact Seizures;Impairment;improved;Individual;innovation;insight;interest;Intervention;Kainic Acid;Laboratories;Lateral;Lesion;Literature;Medial;Methods;Modeling;Motor;mouse model;Movement;Mus;neocortical;Nervous System Disorder;Neurons;new therapeutic target;novel;optogenetics;Outcome;Output;Pathway interactions;Patient-Focused Outcomes;Patients;Physiology;Population Dynamics;Prosencephalon;Purkinje Cells;recruit;Research;Research Personnel;Research Technics;response;Rewards;Rodent Model;Role;segregation;Seizures;Sensory;skills;Solid;Somatosensory Cortex;spatiotemporal;Structure;Surface;targeted treatment;Technical Expertise;Techniques;Temporal Lobe Epilepsy;Testing;Thalamic structure;Therapeutic Intervention;Training;United States;Viral;Water;Writing

PROJECT_TITLE: Cerebellar computations in health and epilepsy

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


NIH_SPENDING_CATS: Brain Disorders;Headaches;Migraine;Neurosciences;Pain Research;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: Traumatic brain injury (TBI) is a serious health care problem that affects millions of people annually and it can lead to significant long-term morbidities attributed to diffuse pathologies that are not well understood. Post- traumatic headache (PTH) such as migraine following TBI also has pathological repercussions that are not well defined. This study aims to investigate membrane disruption and the molecular mechanisms driving this diffuse pathology, while further investigating migraine to alleviate the burden of PTH.

PI_NAMEs: HERNANDEZ, MARTINA LAURA (contact)

PROGRAM_OFFICER_NAME: OSHINSKY, MICHAEL L

PROJECT_TERMS: Acute;Address;Affect;Animals;antagonist;Anti-Inflammatory Agents;Automobile Driving;Award;Biological Assay;burden of illness;Calcitonin Gene-Related Peptide;career;Cathepsins B;Cell Death;cell injury;Cell membrane;Cells;Cessation of life;Chronic;Clinical;Collaborations;Cytosol;Data;Dextrans;Diffuse;disability;Electrophysiology (science);Etiology;experience;fluid percussion injury;forging;gliovascular;Goals;Headache;Healthcare;Histologic;Hour;Impairment;in vivo;Infusion procedures;inhibitor;Injury;Injury compensation;insight;Intervention;Intracranial Hypertension;Intracranial Pressure;Laboratories;Learning;Light;Lysosomes;Mediating;Mediator;Membrane;Mentors;Microscopic;Migraine;Modeling;Molecular;Morbidity - disease rate;Nausea;Neuronal Injury;Neurons;Neurosciences;novel;Outcome;pain behavior;Pathologic;Pathology;Peptide antibodies;Peptide Hydrolases;Persons;Pharmacologic Substance;Phase;Phenotype;Play;Population;post-doctoral training;Post-Traumatic Headaches;Postdoctoral Fellow;pre-clinical research;pre-doctoral;Protocols documentation;Publications;Rattus;Research;Research Personnel;Research Project Grants;Role;sound;Techniques;Therapeutic;Tracer;Training;transcriptomics;Traumatic Brain Injury;triptans;United States;Work

PROJECT_TITLE: Effects of ICP elevation on NeuN Negative Membrane Disrupted Neurons


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_CITY: BOSTON

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: TUFTS UNIVERSITY BOSTON

ORG_STATE: MA

PHR: Project Narrative Schistosomes are parasitic worms that infect the bloodstreams of over 200 million people globally causing the serious disease schistosomiasis. In this work we aim to understand how the worms block control blood flow and obtain nutrients necessary for their survival and growth. We aim to overcome these capabilities to debilitate the worms and cure infection.

PI_NAMEs: SKELLY, PATRICK J (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Adenosine;Applications Grants;arm;Biological Assay;Blood;Blood Circulation;Blood coagulation;Blood flow;Blood Platelets;Calpain;Chronic;Coagulation Process;comparison control;Country;Cytolysis;diadenosine triphosphate;Disease;Electrodes;Environment;Enzymes;experimental study;Fibronectins;Funding;Genes;Growth;Helminths;Hemostatic Agents;Hemostatic function;Histopathology;human disease;Immune response;Impairment;In Vitro;in vivo;infected vector rodent;Infection;interest;Intervention;Kininogens;Label;Measures;metabolomics;Molecular;Monitor;Mus;Niacinamide;Nicotinamide Mononucleotide;novel;Nutrient;Parasite Control;Parasites;pathogen;Persons;Pharmaceutical Preparations;Physiological;Plasma;Platelet Activating Factor;Platelet Activation;platelet function;Platyhelminths;Play;Process;protein function;Proteins;Proteomics;Reaction;Recombinants;Research;response;RNA Interference;Role;Schistosoma;Schistosomiasis;Signaling Molecule;Supplementation;Surface;System;Testing;Thrombelastography;thrombolysis;Thrombosis;thrombotic;Thrombus;uptake;Vaccines;Vertebrates;Weight;Work

PROJECT_TITLE: Functional Characterization of the Schistosome Tegument

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Health Services;Mental Health;Pediatric;Prescription Drug Misuse;Prevention;Primary Health Care;Stimulant Use and Misuse;Substance Misuse;Women's Health Research

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Narrative (Parent Grant DA049721) Non-prescribed use, for cognitive enhancement (e.g., while studying) or recreation (e.g., partying), of stimulant medications by young adults is a prevalent problem; this Schedule II controlled medication is usually obtained from peers with prescriptions, yet little data are available to explain this diversion behavior. Efforts to prevent stimulant misuse are therefore missing key information. The proposed research will study diversion behavior among young adults with ADHD and its longitudinal predictors to improve the prevention of stimulant misuse and its associated adverse medical and legal consequences.

PI_NAMEs: MOLINA, BROOKE S.G. (contact)

PROGRAM_OFFICER_NAME: KURAMOTO-CRAWFORD, SATOKO JANET

PROJECT_TERMS: addiction;Address;Adherence;Adolescence;Adolescent;Adult;Adult women;Age;aged;Aging;Anxiety;Area;Attention deficit hyperactivity disorder;Attitude;Behavior;Behavioral;behavioral economics;boys;Caring;Characteristics;Child Rearing;Childhood;Clinical Trials;cocaine use;cognitive enhancement;common treatment;Competence;conduct problem;Cross-Sectional Studies;Data;Databases;Decision Making;Development;Diagnosis;Diagnostic;diagnostic signature;Disease;Drug Prescriptions;emerging adult;Enrollment;Etiology;Evaluation;Exclusion;experience;Formulation;Funding;Future;Gender;gender difference;girls;Health Personnel;improved;insurance claims;Knowledge;Label;Legal;Literature;Longitudinal Studies;Malingering;Medical;medical specialties;men;methamphetamine use;Monitor;mood symptom;National Institute of Drug Abuse;Outcome;parent grant;Parents;Pathway interactions;Patients;pediatrician;peer;Persons;Pharmaceutical Preparations;pill;Population;Prevalence;prevent;Prevention;Primary Care;primary care patient;primary care provider;primary care setting;Process;prospective;Prospective Studies;provider factors;psychiatric comorbidity;Psychiatric therapeutic procedure;Psychiatrist;Published Comment;Recommendation;Recording of previous events;Recreation;recruit;Reporting;Research;Resources;Risk;Risk Factors;Role;Sample Size;Sampling;Schedule;Science;social;social anxiety;statistics;Stimulant;stimulant misuse;stimulant use;Strategic Planning;substance use;Substance Use Disorder;Symptoms;Testing;Time;Training;trend;Update;Variant;Woman;women's diagnosis;women's treatment;young adult;young woman

PROJECT_TITLE: A prospective examination of stimulant diversion and related risk factors for young adults with childhood- or adult-diagnosed ADHD


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF EDUCATION

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Down Syndrome;Heart Disease;Intellectual and Developmental Disabilities (IDD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases

ORG_CITY: ATLANTA

ORG_DEPT: MISCELLANEOUS

ORG_NAME: GEORGIA STATE UNIVERSITY

PHR: PROJECT NARRATIVE Congenital heart defects occur in almost one half of infants with Down syndrome and result in further delays and weaknesses in motor, cognitive, and language development. This project aims to apply mobile technology and computer vision to compare the developmental trajectory of independent sitting, rhythmic arm movement, and canonical babbling and investigate the interrelations between sitting/arm movement and babbling in infants with Down syndrome with and without congenital heart defects. We hypothesize that infants with Down syndrome and congenital heart defects will show a delayed acquisition of sitting, arm movement, and babbling and weaker interrelations between them compared to infants with Down syndrome without congenital heart defects.

PI_NAMEs: OZCALISKAN, SEYDA ;WU, JIANHUA  (contact)

PROGRAM_OFFICER_NAME: BARDHAN, SUJATA

PROJECT_TERMS: Age;Age Months;aged;arm;arm movement;Behavioral;Cardiac Surgery procedures;Characteristics;Clinical Services;Clinical Trials;cloud storage;Code;Cognitive;cognitive development;Computer software;Computer Vision Systems;Congenital Heart Defects;Data;Data Analyses;Data Collection;design;Development;Developmental Delay Disorders;disability;Down's Syndrome;Focus Groups;Foundations;Genetic Diseases;Goals;High Prevalence;Home;Home environment;Home visitation;Human;Individual;Infant;Intervention;Knowledge;Language;Language Development;Life;Linear Regressions;Logistics;Longitudinal Studies;Manuals;mobile computing;Modeling;Motor;Motor Skills;Movement;Newborn Infant;parenting intervention;Parents;Participant;Periodicity;personalized intervention;Population;Positioning Attribute;Posture;Precision therapeutics;Process;recruit;Regression Analysis;Research;response;Role;Secure;skill acquisition;skills;smart device;Toddler;tool;Travel;trial planning;United States

PROJECT_TITLE: Role of congenital heart defects in motor skills and language acquisition of infants with Down syndrome

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IVBH-B (56)]


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

PHR: PROJECT NARRATIVE Sleep problems are common in Alzheimer's disease patients and are thought to influence disease severity and progression. The work proposed here seeks to identify genes that underlie an individual's risk for developing Alzheimer's-related loss of sleep using a well-characterized, genetically diverse mouse population that better models the complexity of human genetic diversity; traditional mouse models of Alzheimer's disease have provided substantial insights into possible mechanisms causing sleep loss in Alzheimer's disease. The results from the studies we propose will significantly extend current knowledge and have the potential to identify specific gene targets with the potential for translation to therapies for the elderly population suffering from various neurodegenerations.

PI_NAMEs: KACZOROWSKI, CATHERINE COOK (contact);O'CONNELL, KRISTEN M

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: actigraphy;Age;Aging;Alzheimer disease prevention;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer's disease therapeutic;Amyloid;Autopsy;Behavior;Biological;Biological Models;Brain;burden of illness;Clinical;Cognition;Cognitive;Cognitive aging;Cognitive deficits;cohort;Cohort Studies;Communities;Data;data integration;Data Set;Dementia;Detection;Disease Progression;DNA;Elderly;Electroencephalography;familial Alzheimer disease;Gene Targeting;gene therapy;Genes;Genetic;genetic analysis;genetic resource;Genetic Variation;genome editing;Genomic Segment;Hereditary Disease;Heritability;Heterogeneity;high risk;Human;human data;Human Genetics;human model;humanized mouse;Image;Impaired cognition;improved;Individual;Individual Differences;innovation;insight;Knowledge;Knowledge Portal;Laboratories;Late Onset Alzheimer Disease;Link;machine learning classifier;Mediating;Medical;Memory;Memory impairment;Meta-Analysis;mild cognitive impairment;Modeling;Molecular;mouse model;multidimensional data;Mus;Mutation;Nerve Degeneration;Neurobehavioral Manifestations;neuropathology;non rapid eye movement;novel;Outcome;Pathology;Pathway interactions;Patients;Phenotype;Play;Population;pre-clinical;Predisposition;Publications;Quality of life;Quantitative Trait Loci;Questionnaires;Research;Research Personnel;resilience;Resources;Risk;RNA;Role;Sampling;segregation;Severity of illness;Sleep;Sleep Deprivation;Sleep Disorders;Symptoms;synergism;System;Systems Biology;Testing;The Jackson Laboratory;therapeutically effective;tool;trait;Translating;translational potential;usability;Validation;Variant;Visual;Work

PROJECT_TITLE: Systems Genetics Analysis of Alzheimer's Disease-Related Sleep Loss and the Transition to Dementia


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

PHR: PUBLIC HEALTH RELEVANCE Iron deficiency is very common nationally and globally during fetal-neonatal life, causes significant neurobehavioral abnormalities in children (e.g., cognitive and psychosocial deficits), is not reliably prevented by iron treatment in early life, and results in significant costs to society stemming from lost education/job potential and increased later developing mental health problems. We propose to perform studies in primary neuron cell cultures and a dietary rat model of fetal-neonatal iron deficiency anemia to define the specific role of iron treatment timing and dose in programming brain mitochondrial function and rescuing or exacerbating the long- term neurobehavioral effects caused by early-life ID. Successful completion of these studies will a) identify a critical period during pregnancy or early infancy when iron treatment is effective, b) provide mechanistic insights into how early life iron nutrition programs brain mitochondrial functional capacity across the lifespan and c) provide a biological foundation for the need for early-life biomarkers of brain iron status to prevent long-term dysfunction.

PI_NAMEs: GEORGIEFF, MICHAEL K. (contact)

PROGRAM_OFFICER_NAME: ROSS, SHARON A

PROJECT_TERMS: Accounting;Activities of Daily Living;Acute;Adult;Affect;Anxiety;autism spectrum disorder;Axon;Behavior;Behavioral;Biogenesis;Biological;Biological Markers;Birth;Brain;Brain Diseases;brain dysfunction;brain iron;Cell Culture Techniques;Cells;Child;Chronic;Citric Acid Cycle;clinical translation;Clinical Trials;Cognition;Cognitive;cognitive development;cost;critical period;Data;Dendrites;Development;dietary;DNA Methylation;Dose;Education;electron energy;Electron Transport;Enzymes;Epidemiology;Epigenetic Process;Equilibrium;Event;fetal;Fetus;Foundations;Functional disorder;Genes;Glucose;Growth;Hippocampus;Homeostasis;Human;Impaired cognition;Impairment;in vitro Model;in vivo;infancy;insight;Investigation;Iron;iron deficiency;Iron deficiency anemia;Learning;Life;life span;Link;Long-Term Effects;Memory;memory encoding;Mental Depression;Mental Health;Metabolic;metabolic rate;Mitochondria;mitochondrial therapeutics;Modeling;Morphology;Motility;Motor Skills;mouse model;Mus;Neonatal;neonatal brain;neural circuit;neurobehavior;neurobehavioral;Neurobiology;Neurocognitive;neuron development;neuronal growth;Neurons;neuropsychiatric disorder;neuropsychiatry;neurotransmitter release;Newborn Infant;Nutrient;nutrition;Occupations;Organ;Outcome Measure;Oxidation-Reduction;oxidative damage;Oxidative Phosphorylation;Oxygen;Oxygen Consumption;Pancreas;Pathologic;Persons;postnatal;Pregnancy;Pregnant Women;prenatal;prevent;Process;Production;programs;Proteins;Psychopathology;psychosocial;public health relevance;Publishing;Quality Control;racial health disparity;Rattus;Recovery;Regulation;Research;Respiration;Risk;Role;Schizophrenia;Second Pregnancy Trimester;Signal Transduction;Societies;stem;Structure;Synapses;synaptogenesis;Testing;trafficking;Transcriptional Regulation;treatment strategy

PROJECT_TITLE: Newborn Iron Deficiency

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Clinical Research;Hematology;Rare Diseases;Sickle Cell Disease

PHR: PROJECT NARRATIVE The proposed research will provide important mechanistic insights into how inflammatory caspases are dysregulated by excess extracellular heme, a key pathophysiological feature of sickle cell disease. This is relevant to public health because the discoveries made will have the potential to lead to therapies to control the inflammatory complications in sickle cell disease including pain and stroke. Thus, the proposed research is relevant to the mission of the National Heart Blood and Lung (NHLBI) that pertains to understanding, treating, and preventing adverse clinical outcomes in sickle cell disease.

PI_NAMEs: BOUCHIER-HAYES, LISA  (contact);FLANAGAN, JONATHAN MICHAEL

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: 5 year old;acute chest syndrome;Alleles;Apical;Binding;Binding Sites;Biology;Blood;Brain Death;Caring;CASP1 gene;CASP4 gene;CASP5 gene;Caspase;Catalytic Domain;Cell Death;Cell-Free System;Cells;Child;Chronic;chronic pain;Clinical;Code;cohort;CRISPR/Cas technology;cytokine;Data;dimer;Disease;disease phenotype;Endothelial Cells;Erythrocytes;Event;experimental study;extracellular;FDA approved;gene delivery system;Gene Expression;Heart;Heart Arrest;Heme;Hemolysis;Homologous Gene;Human;improved outcome;In Vitro;Individual;individual patient;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Innate Immune Response;insight;Interdisciplinary Study;Interleukin-1 beta;Interruption;Investigation;Knock-out;Knowledge;Life;Life Expectancy;low income country;Lung;Macrophage;Measures;Mediator;Mission;Modeling;monomer;Multiple Organ Failure;Mus;National Heart, Lung, and Blood Institute;Necrosis;new therapeutic target;Organ;organ injury;Outcome;Pain;Pathway interactions;Patients;Pediatric Hospitals;persistent symptom;Persons;Pharmaceutical Preparations;Physiological;Plasma;predictive modeling;prevent;protein complex;Public Health;recruit;Reporting;Research;response;Role;Sampling;scaffold;Sickle Cell Anemia;sickling;Stroke;Structural Models;Symptoms;systemic inflammatory response;Testing;Texas;Tissues;Variant;vaso-occlusive crisis;VDAC1 gene

PROJECT_TITLE: Inflammatory caspase activation in sickle cell disease

STUDY_SECTION: HTBT

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


NIH_SPENDING_CATS: Aging

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE Testing drugs to see if they increase healthy lifespan in genetically heterogeneous mice is an effective way to find interventions that may alter human aging, because these mice are good models for the clinic, and give reasonably rapid and reliable results, especially when used in three different sites. Identification of interventions that retard aging will suggest research directions leading to clinical treatments designed to prevent or retard deleterious changes with age.

PI_NAMEs: KORSTANJE, RONNY  (contact)

PROGRAM_OFFICER_NAME: COGLIATI, TIZIANA PAOLA

PROJECT_TERMS: Acarbose;Adult;Age;age related;age related changes;Aging;aging mechanism;anti aging;Application procedure;astaxanthine;Beds;Biological Specimen Banks;Biology of Aging;Bladder;Captopril;Cause of Death;Clinic;Clinical Treatment;Collaborations;Communities;comparative;Data;Data Coordinating Center;data management;Data Pooling;Data Set;Diagnostic Specificity;Disease;Dose;Drug Combinations;Drug Kinetics;drug testing;Elements;end of life;Estradiol;Evaluation;experimental study;extend lifespan;Gene Expression;Glycine;Goals;Health;healthspan;Heart;Histopathology;Human;Image Analysis;insight;interest;International;Intervention;intervention effect;Kidney;Laboratories;late life;life span;Link;Longevity;Machine Learning;Mammals;meetings;member;Michigan;middle age;Modeling;Molecular;Mus;New Agents;novel therapeutics;Organ;Outcome;Pathologic;Pathology;Pharmaceutical Preparations;Physiological;preservation;prevent;Procedures;programs;Protocols documentation;Publications;Reliability of Results;Reproducibility;Research;response;Schedule;Scientist;sex;Sirolimus;Site;Specific qualifier value;Specimen;Standardization;Testing;Texas;The Jackson Laboratory;therapy design;tissue archive;tissue preparation;Tissues;Transcript;transcriptome sequencing;transcriptomics;transmission process;Universities;web site;Work

PROJECT_TITLE: Interventions That Retard Mammalian Aging

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-3 (J1)]