NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Pediatric;Rare Diseases

ORG_CITY: HERSHEY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Project Narrative Despite improvements in cardiovascular care, heart failure and arrhythmia remain the most common late manifestations of heart disease, and are poorly defined in heritable/congenital heart disease populations. Therefore, the identification of new pathways underlying heart failure and arrhythmia are essential to better assess risk, improve diagnostic evaluation, and change the natural history of this disease. Our proposal will test the role of novel Giant AnkG in cardiac function and dysfunction.

PI_NAMEs: BRADLEY, ELISA ANN (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Actins;Adult;Affect;ANK2 gene;ANK3 gene;Ankyrins;Area;Arrhythmia;betaIV spectrin;Biology;Cardiac;Cardiomyopathies;Cardiovascular Diseases;Cardiovascular system;career;Caring;Cells;Child;Clinical;Communities;Complex;Congenital Cardiovascular Abnormality;congenital heart abnormality;Cytoskeleton;Data;Defect;Diagnostic;Dilated Cardiomyopathy;Disease;disease natural history;disease phenotype;Elements;Etiology;Evaluation;Exhibits;Functional disorder;gene product;Genes;Goals;Heart;Heart Block;Heart Diseases;Heart failure;heart function;Heritability;Human;human disease;improved;In Vitro;in vivo;insight;Intercalated disc;Investigation;Ion Channel;Left ventricular structure;Link;loss of function;loss of function mutation;Membrane;Membrane Proteins;Mentors;Modeling;Molecular;Morphology;Mus;Muscle Cells;Mutation;Myocardial Contraction;Myocardial dysfunction;Myocardium;Neurons;novel;Pathologic;Pathway interactions;Patients;Persons;Phenotype;Physicians;Physiological;Play;Population;Post-Translational Protein Processing;Protein Isoforms;Proteins;recruit;Regulation;response;Risk Assessment;Role;Scientist;Signal Transduction;Sodium Channel;Spectrin;Stimulus;Structure;sudden cardiac death;Testing;Thinness;Tissues;training opportunity;Variant;Ventricular Arrhythmia;voltage;Work

PROJECT_TITLE: Defining New Pathways for Complex Human Heart Failure and Arrhythmia

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(JA)]


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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);Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CHAPEL HILL

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHYSIOLOGY

ORG_FIPS: US

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative The proposed research will identify new genes and genetic variants that increase risk of Alzheimer’s Disease. Our work will break down existing barriers by massively increasing the speed, throughput, and accuracy with which we can identify causal SNPs and their mechanisms of action. This will provide new Alzheimer’s Disease risk genes for further study and drug development, establish a tractable biological system in which to study these genes, and establish a new paradigm for GWAS SNP interpretation that can be applied to other cell types and other diseases.

PI_NAMEs: COHEN, TODD JONATHAN;PHANSTIEL, DOUGLAS H. (contact);WON, HYEJUNG

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: 3-Dimensional;Acceleration;Affect;Alzheimer's Disease;Alzheimer's disease risk;Amyloid beta-Protein;apolipoprotein E-4;Base Pairing;Binding;Biological Assay;biological systems;brain cell;brain tissue;causal variant;Cell Culture Techniques;cell type;Chromatin;Chromatin Loop;Chromatin Structure;Clustered Regularly Interspaced Short Palindromic Repeats;Data Set;Diagnosis;Disease;Distal;drug development;Enhancers;Event;experimental study;Foundations;Genes;Genetic;Genetic Transcription;genetic variant;genome editing;genome wide association study;genomic locus;Genomics;Goals;high throughput technology;Histone Acetylation;Human;human induced pluripotent stem cells;induced pluripotent stem cell;Link;Maps;Mediating;Microglia;Modeling;Molecular;Nerve Degeneration;novel;Nucleic Acid Regulatory Sequences;Pathogenicity;Play;protective allele;Protocols documentation;Regulatory Element;Reporter;Research;Resolution;response;Rest;Risk;risk variant;Role;Senile Plaques;Single Nucleotide Polymorphism;Speed;Stimulus;Techniques;Testing;tool;tool development;transcription factor;transcription regulatory network;Transcriptional Regulation;TREM2 gene;Untranslated RNA;Variant;Work

PROJECT_TITLE: Identifying Alzheimer’s Disease Causal Variants and Target Genes Using iPSC-derived Microglia

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: NEW HAVEN

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Lipid droplets are central to regulating intracellular energy availability. The lipid transport protein ATG2 is known to regulate lipid droplet homeostasis, and its interactors are known to regulate lipid droplet homeostasis and lipoprotein formation. This project seeks to mechanistically determine how ATG2, and its interactors regulate lipid droplet homeostasis in cells.

PI_NAMEs: KORFHAGE, JUSTIN  (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Adipose tissue;Amphipathic Alpha Helix;automated image analysis;Autophagosome;Binding;Biochemistry;Biogenesis;Biological;Biological Assay;Biological Process;Biology;Biotinylation;C-terminal;Carrier Proteins;Cell Physiology;Cells;Cellular biology;Characteristics;Co-Immunoprecipitations;Complex;Consumption;Data;Defect;design;Development;Diabetes Mellitus;Engineering;Esters;Family;fatty acid analog;fatty acid oxidation;Fatty Acids;Fluorescence Microscopy;Fluorescence Resonance Energy Transfer;Goals;Homeostasis;hydrophilicity;Hydrophobicity;Image Analysis;In Vitro;in vivo;knock-down;Knock-out;Label;Lead;Link;lipid metabolism;Lipid Mobilization;lipid transport;Lipids;Lipoproteins;Liposomes;Maintenance;Mediating;Melia;member;Membrane;Mentorship;Metabolic;Metabolic Diseases;Metabolic syndrome;Mitochondria;Movement;mutant;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel strategies;Obesity;Organelles;Organism;Phenocopy;Phospholipids;Physiologic pulse;Process;Protein Family;Proteins;Publishing;quantitative imaging;Regulation;Role;Site;skills;Small Interfering RNA;structural biology;Structure;Testing;trafficking;Training;Triglycerides;Validation;Work

PROJECT_TITLE: ATG2 mediated lipid transport is essential for lipid droplet homeostasis


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Emerging Infectious Diseases;Genetics;Infectious Diseases;Muscular Dystrophy;Rare Diseases;Vector-Borne Diseases

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Modification of proteins by sugars (protein glycosylation) is essential in all eukaryotes, and deficiencies in glycosylation cause severe human disease. We are interested in identifying lipid transporters that are necessary for delivering sugar precursors for glycoprotein synthesis within cells, with the eventual goal of understanding their molecular mechanism and learning how their deficiency causes disease.

PI_NAMEs: MENON, ANANT K (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: 2019-nCoV;adduct;Alkynes;analog;Antibodies;Azides;Benzophenones;Biochemical;Bioinformatics;Biological;Biological Assay;biophysical techniques;candidate identification;Carrier Proteins;Cell-Adhesion Molecule Receptors;Cells;Cellular biology;Characteristics;chemoproteomics;Complex;Congenital disorders of glycosylation;crosslink;Cytoplasm;Cytoskeleton;Data;Defect;Dengue;Disease;Distant;Dolichol;Dolichol Monophosphate Mannose;Dystroglycan;Embryo;Endoplasmic Reticulum;Eukaryota;experience;experimental study;Extracellular Matrix;Face;Future;G-Protein-Coupled Receptors;Genetic Complementation Test;Genome;genomic locus;Glucose;Glycolipids;Glycoproteins;glycosylation;Glycosylphosphatidylinositols;Goals;GPI Membrane Anchors;Hematopoietic;Hereditary Disease;human disease;human stem cells;in silico;in vivo;innovation;interest;Ion Channel;Isomerism;Learning;Link;Lipids;Malaria;Mammals;Mannose;Mediating;Membrane;Membrane Proteins;Methods;Microsomes;Molecular;Mus;Muscular Dystrophies;mutant;Neurologic Symptoms;novel;Organism;paroxysmal nocturnal hemoglobinuria;Phenotype;phospholipid scramblase;Phylogenetic Analysis;Physiological;Plant Resins;Polysaccharides;Positioning Attribute;Post-Translational Protein Processing;Procedures;Process;Proliferating;protein function;Protein Glycosylation;Proteins;Proteomics;Reaction;reconstitution;Reporter;secretory protein;Side;Source;Specificity;Structure;sugar;Testing;Trypanosoma;Universities;Vesicle;Virus;Virus Diseases;Work;Yeasts

PROJECT_TITLE: Scramblases for protein glycosylation

STUDY_SECTION: MBPP

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

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

ORG_CITY: DALLAS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Biofilms have been associated with a number of intestinal diseases such as inflammatory bowel disease and colorectal cancer. I propose further characterize the role of biofilm formation in E. coli colonization of the intestinal tract and to use this model system to understand more generally the role of biofilms in disease pathogenesis at the intestinal mucosal interface. The goal of this project is to develop a deeper understanding of bacterial competition in biofilms and use this knowledge to engineer the mucosally-associated microbiota to modulate intestinal diseases.

PI_NAMEs: NI, JOSEPHINE  (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Address;Anabolism;Animal Model;Bacteria;Bacterial Infections;Biologic Characteristic;Biological;Biological Assay;Biological Models;Body Weight decreased;career development;Cell Adhesion;Characteristics;Chelating Agents;Chemicals;Citrobacter rodentium;Colitis;Colon;Colonic Diseases;Colorectal Cancer;Complement;Complex;Confocal Microscopy;Data;Dental caries;Dietary Iron;Disease;Engineered Gene;Engineering;Enterobactin;Environment;Escherichia coli;Exclusion;experience;experimental study;fitness;gain of function;Gene Modified;Genes;Goals;Growth;gut colonization;gut microbiome;Harvest;Image;Immunofluorescence Immunologic;In Vitro;in vivo;Inductively Coupled Plasma Mass Spectrometry;Infection;Infectious colitis;Inflammatory Bowel Diseases;inhibitor;innovation;Intestinal Diseases;Intestinal Mucosa;Intestines;Investigation;Iron;iron supplementation;Knowledge;knowledge base;Length;Link;loss of function;microbial;Microbial Biofilms;microbial community;Microbiology;microbiome analysis;microbiota;microbiota composition;Modeling;Mucins;mucosal microbiota;Mucous body substance;Mucous Membrane;murine colitis;Mus;mutant;Mutation;Nitrogen Fixation Genes;Nutrient;pathogen;Pathogenesis;Pathway interactions;Pattern;Pennsylvania;Pentetic Acid;Physiological;Pilum;Play;Proteins;Proteomics;Radial;Research;Research Personnel;Role;rRNA Genes;skills;Small Intestines;Specificity;Surface;Techniques;Testing;Universities;Urinary tract

PROJECT_TITLE: Determinants of bacterial biofilm formation at the intestinal mucosal interface and their roles in pathogen exclusion

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

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

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE  Technology increasingly enables researchers to generate very large amounts of genomic data. The Biocon- ductor project makes available statistical software that helps researchers analyze and interprete the data they have generated. As a result of Bioconductor's unique open development and open source approach, a large number of research professionals around the world contribute to and beneﬁt from the project.

PI_NAMEs: CAREY, VINCENT JAMES;IRIZARRY, RAFAEL ANGEL (contact)

PROGRAM_OFFICER_NAME: WELLINGTON, CHRISTOPHER

PROJECT_TERMS: Acceleration;Address;Adoption;Advanced Development;Algorithms;analytical method;Archives;Area;Atlases;Bioconductor;Bioinformatics;Biological;Biological Assay;Biology;Cells;cloud based;Code;Collaborations;Communities;community advisory board;community engagement;community engagement process;Community Health Education;Comprehension;Computer software;Computing Methodologies;computing resources;Data;data ecosystem;Data Element;data quality;Data Science;Data Scientist;Data Set;Dedications;Dependence;design;Development;Discipline;Documentation;Education;Educational Models;Environment;experimental study;FAIR principles;Flow Cytometry;Fostering;Funding;Genome;genome analysis;genome resource;genome sciences;genome-wide;genomic data;Genomic medicine;genomic platform;genomic tools;Genomics;Goals;Grant;Growth;Health;Human;Image;improved;Individual;Informatics;Infrastructure;Ingestion;Instruction;International;interoperability;Knowledge;Linux;Maintenance;member;Methodology;Methods;Modernization;National Human Genome Research Institute;new technology;open source;Performance;personalized genomic medicine;Population Genetics;portability;Principal Investigator;Process;Programming Languages;Proteomics;Reproducibility;Research;research and development;Research Personnel;Resources;Running;Services;software development;Software Engineering;Specific qualifier value;Structure;symposium;System;Systematic Bias;Technology;Testing;Time;tool;Training;usability;Visualization;Work

PROJECT_TITLE: Bioconductor: An Open-Source, Open-Development Computing Resource for Genomics


NIH_SPENDING_CATS: Brain Disorders;Cardiovascular;Chronic Pain;Complementary and Integrative Health;Dietary Supplements;Neurosciences;Nutrition;Pain Research

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: Members of the transient receptor potential ion channel (TRP) family act as biological sensors by decoding various physiological cues in the environment to regulate vascular and neuronal function. The proposed study is relevant to NIH’s mission because it will provide the molecular basis by which bioactive lipids modulate the function of vascular and neuronal TRP ion channels. The proposed research is relevant to public health because dietary consumption of polyunsaturated fatty acids, among other bioactive lipids, is known to prevent cardiovascular diseases and ameliorate neurological disorders.

PI_NAMEs: CORDERO-MORALES, JULIO F (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Agonist;antagonist;base;Biosensor;Blood Vessels;C-terminal;Cardiovascular Diseases;Cell membrane;Cerebellar Ataxia;Chemicals;Clinical Trials;Consumption;Cues;Detection;Development;Diabetes Mellitus;dietary;Diglycerides;Disease;Environment;Family;Functional disorder;Health;Hypersensitivity;Hypertension;In Vitro;in vivo;Inflammation;insight;Ion Channel;Kidney Diseases;Lipids;Mediating;member;Mission;Molecular;Nervous System;Nervous System Disorder;Neurons;Omega-3 Fatty Acids;Osmoregulation;Pain;Peripheral Nervous System Diseases;Pharmaceutical Preparations;Pharmacologic Substance;Phosphatidylinositols;Physiological;Physiological Processes;Physiology;Play;Polyunsaturated Fatty Acids;prevent;Public Health;receptor;Research;Role;Sensory;side effect;Stimulus;Temperature;TRP channel;TRPV1 gene;United States National Institutes of Health;Vascular Diseases;Vascular System;Work

PROJECT_TITLE: Sensory Ion Channel Modulation by Bioactive Lipids


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Cancer;Emerging Infectious Diseases;Genetics;HIV/AIDS;Hematology;Infectious Diseases;Lymphatic Research;Lymphoma;Rare Diseases

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative Kaposi’s sarcoma-associated herpesvirus (KSHV) has an etiologic role in several human cancers. KSHV infects tumor cells and persists in these cells in a latent state. This work investigates the mechanisms this virus uses to allow it to be maintained in tumor cells. A better understanding of these viral mechanisms may allow development of strategies which prevent KSHV cancers.

PI_NAMEs: KAYE, KENNETH M (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Africa South of the Sahara;Animal Model;antigen binding;Binding;Biochemical;Biological;Biological Assay;C-terminal;Cell Nucleus;Cell Proliferation;Cell Survival;Cells;Daughter;daughter cell;Development;Disease;DNA;DNA Binding Domain;DNA biosynthesis;Elements;Epidemic;Episome;Etiology;experimental study;gamma-2 herpesvirus;gammaherpesvirus;Genes;Genetic;genetic approach;Genome;Glycogen Synthase Kinase 3;Herpesviridae Infections;Histone H2A;Human;Human Herpesvirus 8;Immunocompromised Host;in vivo;insight;interest;Investigation;Kaposi Sarcoma;latency-associated nuclear antigen;Link;Lysine;Maintenance;Malignant Neoplasms;Mediating;Mitotic Chromosome;Molecular;Multicentric Angiofollicular Lymphoid Hyperplasia;Mus;N-terminal;neoplastic cell;novel;novel strategies;Nucleosomes;Oncoproteins;Oral cavity;Organ;Phosphorylation Site;Plasmids;prevent;primary effusion lymphoma;Proliferating;Proteins;Reader;Repetitive Sequence;Role;segregation;Sequence Deletion;Sequence Homologs;Specificity;Surface;Terminal Repeat Sequences;TP53 gene;tumor;ubiquitin-protein ligase;Viral;viral DNA;Viral Genome;Virus;Virus Replication;Visceral;Work

PROJECT_TITLE: Genetic and Biochemical Studies of KSHV LANA


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Data Science;Dementia;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Patient Safety;Prevention;Primary Health Care;Rehabilitation

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative The ability of clinicians, health systems and researchers to identify patients with mild cognitive impairment (MCI) and Alzheimer’s Disease Related Dementias (ADRD) is limited. This project will apply machine learning to natural language processing (NLP) of electronic health record data and automated speech analysis (ASA) of patient-doctor conversations during primary care visits to identify patients with MCI and ADRD using automated and scalable procedures. The analytic algorithms will be developed with neurocognitive assessment data on 800 primary care patients in New York City and validated in an independent sample of 200 patients in Chicago. 1

PI_NAMEs: FEDERMAN, ALEX D (contact);WISNIVESKY, JUAN P

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Acoustics;Acute;Address;adverse event risk;aging population;Algorithms;Alzheimer's disease related dementia;automated speech recognition;care coordination;Caregivers;Chicago;Clinical;Clinical assessments;clinical encounter;Code;Cognition;Cognitive;cognitive function;cognitive testing;Data;Data Analyses;Data Element;Data Scientist;Data Set;deep learning;demographics;Development;Diagnosis;Diagnostic;diagnostic algorithm;Dimensions;Documentation;Early Diagnosis;electronic health data;Electronic Health Record;electronic structure;falls;feature extraction;financial incentive;health care settings;Health Services;Health system;Impaired cognition;improved;Individual;Insurance Carriers;insurance claims;Machine Learning;machine learning algorithm;machine learning classifier;Measures;Mental disorders;mental state;Methods;mild cognitive impairment;multidisciplinary;Natural Language Processing;Neurocognitive;New York City;Notification;older adult;Parkinson Disease;Patients;Persons;Physicians;Population;Positioning Attribute;prevent;Preventive care;Primary Care;primary care patient;primary care setting;primary care visit;Procedures;Provider;Psychiatric Diagnosis;recruit;Reference Standards;Research;Research Personnel;Resource Allocation;Risk Factors;risk mitigation;Sampling;screening;secondary analysis;Semantics;Sensitivity and Specificity;Services;Signs and Symptoms;Speech;Structure;structured data;Study Subject;success;Technology;Testing;Text;Time;tool;Training;treatment choice;United States;unstructured data;Validation

PROJECT_TITLE: Natural Language Processing and Automated Speech Recognition to Identify Older Adults with Cognitive Impairment

STUDY_SECTION: BCHI

STUDY_SECTION_NAME: Biomedical Computing and Health Informatics Study Section[BCHI]


ADMINISTERING_IC: TW

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Cancer;Climate-Related Exposures and Conditions;Clinical Research;Health Effects of Indoor Air Pollution;Women's Health Research

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE This renewal application proposes to continue a progressive and tiered training program that will further develop researchers and research teams able to carry out the research agenda of the Eastern Africa GEOHealth Hub and to facilitate the translation of the research findings into impactful actions by key stakeholders. The Hub will train 6 Hub Scholars (building on 11 Hub Scholars from the first funding cycle), degree level trainees (5 PhD and 12 MS/MPH degree candidates), research team trainees across the three LMIC primary partners, and additional trainees from stakeholders as well as three more training partner countries who are all expected to become national leaders in environmental and occupational health research. The Hub will continue to train multidisciplinary research teams, develop curricular materials for academic and stakeholder institutions, and foster evidence translation and implementation with a long-range goal of establishing a sustainable Hub for the region.

PI_NAMEs: BERHANE, KIROS T (contact);JACK, DARBY ;KUMIE, ABERA TAKELE;SIMANE, BELAY

PROGRAM_OFFICER_NAME: JESSUP, CHRISTINE

PROJECT_TERMS: Address;Africa South of the Sahara;African;Air;ambient air pollution;California;Cameroon;Case Study;Child;climate change;Collaborations;Colorado;Competence;cost effective;Country;Development;Doctor of Philosophy;Eastern Africa;Educational Status;Educational workshop;Ensure;Environmental Health;Ethiopia;Evaluation;experience;flexibility;Funding;Ghana;Goals;Grant;Guidelines;Indoor Air Pollution;innovation;Institution;Kenya;Leadership;Length of Stay;Link;low and middle-income countries;meetings;Mentors;Modality;Needs Assessment;Occupational Health;Paper;Participant;Policies;Productivity;programs;Public Health Schools;Records;Regulation;Request for Applications;Research;Research Personnel;Rwanda;Scholars Program;skills;success;Training;Training Activity;Training Programs;Translations;Uganda;Universities;Women's Health

PROJECT_TITLE: GEOHEALTH HUB FOR RESEARCH AND TRAINING IN EASTERN AFRICA - U.S.

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

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

PHR: PROJECT NARRATIVE Long term success of human hematopoietic stem cell (HSC) transplantation is curative in many blood and other disorders but challenged by lack of sufficient numbers of HSCs. Studies proposed here are designed to enhance human HSC potency by modulating their non-nuclear organelles specifically the activity of lysosomes and their communication with mitochondria. To achieve this goal, the work will elucidate mechanisms of lysosomal regulation of human HSC potency and likely to identify a new lysosomal-based mode of intervention to improve human HSC engraftment.

PI_NAMEs: GHAFFARI, SAGHI  (contact)

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: adult stem cell;Age;Autophagocytosis;Blood;Cell Cycle;Cell Surface Receptors;Cell Therapy;Cells;Clinic;Communication;design;Disease;Foundations;Generations;Genomics;Goals;Health;hematopoietic stem cell fate;hematopoietic stem cell quiescence;Hematopoietic Stem Cell subsets;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Homeostasis;Human;Image;improved;in vivo;Injury;Intervention;Life;Link;Longevity;Lysosomes;Maintenance;Malignant Neoplasms;Mediating;Membrane Potentials;Metabolic stress;Mitochondria;mitochondrial membrane;Molecular;Mus;novel;novel strategies;Organelles;Output;Pathway interactions;Phenotype;Pluripotent Stem Cells;Process;programs;Property;Recycling;Regulation;repaired;response;self-renewal;stem cell engraftment;stem cell function;stem cell therapy;stem cells;stemness;success;Surface;Testing;therapy resistant;Time;Tissues;Translations;Transplantation;Work

PROJECT_TITLE: Towards Understanding Molecular Mechanisms of Human Hematopoietic Stem Cells' Quiescence

STUDY_SECTION: HTBT

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


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Neurosciences;Pediatric;Social Determinants of Health

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: PROJECT NARRATIVE Workforce diversity in STEM is critical to our success as a nation and our ability to address major public health challenges. However, as a nation, we have fallen short of our STEM workforce diversity goals, a failure that has been long attributed to the “leaky academic pipeline” but in reality, is related to a convergence of complex and interrelated social and environmental factors. The Brain Explorer Academy uses neuroscience and a digitally connected social-ecological framework to deploy and evaluate a multi-year, interdisciplinary training program for high school students from underrepresented minorities to stimulate their interest and persistence in STEM disciplines.

PI_NAMEs: GUERRA, NANCY G.;YASSA, MICHAEL A (contact)

PROGRAM_OFFICER_NAME: BECK, LAWRENCE A

PROJECT_TERMS: Academy;Address;Adoption;Attitude;Bachelor's Degree;bilingualism;Brain;career;Collaborations;Collection;college;Communication;Competence;Complex;Critical Thinking;Curiosities;Degree Completion;Development;digital;digital repositories;digital technology;Disparity;Drops;Economic Factors;education pathway;Enrollment;Environment;Environmental Risk Factor;Evaluation;experience;Failure;Family;Fostering;Goals;Health;high school;High School Student;Hispanic;improved;Individual;innovation;Institution;interest;Intervention;Knowledge;Learning;learning materials;lens;meetings;Mentors;minority disparity;Minority Groups;Modeling;Neurosciences;Neurosciences Research;neurotechnology;next generation;Outcome;outreach;Parents;Participant;Process;programs;Public Health;Randomized, Controlled Trials;recruit;Research;Resources;Schools;Science;science education;Science, Technology, Engineering and Mathematics Education;skill acquisition;skills;social;social factors;Societies;Spanish/English;STEM career;STEM field;Structure;Student recruitment;student retention;Students;success;Teacher Professional Development;Testing;Training Programs;Transportation;undergraduate education;Underrepresented Minority;underrepresented minority student;underserved community;Underserved Population;United States;video module;web site;Woman

PROJECT_TITLE: The Brain Explorer Academy (BEA): An Informal Science Education Partnership

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


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dietary Supplements;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Narrative: Native Tribes have been, and continue to be, exposed to significant amounts of toxic waste as a product of environmental injustice and are at an increased risk of adverse health outcomes due to contaminated soils that grow traditional food sources, degraded qualities of water, food, and air, and loss of infrastructure, and cultural practices that build community strength and resiliency. Such is the case for the Ramapough Lunaape Turtle Clan in NJ (1 of 3 Clans of the Ramapough Lunaape Nation) who live in a 500 acre toxic waste site created by a decade of industrial dumping of thousands of gallons of paint sludge in northern NJ. As no culturally-meaningful interventions have been implemented for theTribal community that could promote health and well-being to date, we propose to build on our long and equitable Tribal-academic partnerships with the Ramapough to advance tradition-centered, evidence-based best practice strategies for sustainable environmental food systems that address food insecurity, nutritional deficiency, and chronic disease health outcomes among the Ramapough Turtle Clan communities disproportionately affected by environmental contamination.

PI_NAMEs: ERDEI, ESTHER ;ZELIKOFF, JUDITH TERRY (contact)

PROGRAM_OFFICER_NAME: O'FALLON, LIAM

PROJECT_TERMS: Address;Affect;Air;American;assault;Blood;Blood Pressure;Body mass index;burden of illness;Calcium;Chronic Disease;Church;citizen science;Communities;Community Actions;community building;Community Health;community-centered;Complex;Consensus;Deficiency Diseases;demographics;design;Development;Disease;disease disparity;Eating;Education;Engineering;Enrollment;Environment;Environmental Health;Environmental Pollution;Environmental sludge;Equity;evidence base;experience;Exposure to;Farm;Folic Acid;Food;food insecurity;food security;Health;Health Food;Health Promotion;Heavy Metals;Height;Home;implementation framework;improved;Indian reservation;Individual;Industrialization;Infrastructure;innovation;Intervention;Iron;life span;Malnutrition;manufacturing facility;Maps;marginalization;Measurement;Medicine;member;Methods;Micronutrients;mind/body;Native Americans;Native-Born;New Jersey;non-Native;nutrition;Nutritional;Outcome;Paint;Personal Satisfaction;Persons;Plants;Poverty;prevent;Process;programs;psychosocial stressors;Public Health;Qualifying;Quality of life;Recreation;Research;resilience;Risk;sex;Sister;Site;Soil;Solvents;Source;superfund site;Surface;Surveys;System;Testing;toxicant;Translations;tribal community;tribal member;tribal Nation;Tribal-academic partnership;Tribes;Turtles;Urine;Vitamins;volunteer;wasting;Water;water quality;Weight

PROJECT_TITLE: Building food sovereignty, sustainability and better health in environmentally-impacted Native Americans


NIH_SPENDING_CATS: Genetics

PHR: PROJECT NARRATIVE The capability of a cell to divide relies on its ability to produce proteins and is directly related to the production of ribosomes in the nucleolus. We seek to understand the role of a novel complex that we found to be involved in maintaining nucleolar integrity, protein synthesis, and cell growth.

PI_NAMEs: CONACCI-SORRELL, MARALICE  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Alzheimer's Disease;Architecture;Binding;Biogenesis;Cell Cycle;cell growth;Cell Nucleolus;Cells;Complex;Data;Defect;Development;Disease;Experimental Designs;Fingers;Generations;Genetic Transcription;Health;human disease;Immunoprecipitation;In Vitro;in vivo;knock-down;Knock-out;Maintenance;Malignant Neoplasms;Mammalian Cell;Measures;Membrane;Molecular;Morphology;Names;Neurodegenerative Disorders;novel;novel strategies;NPM1 gene;Nucleolar Proteins;Organelles;overexpression;Parkinson Disease;Pathologist;Pathway interactions;Point Mutation;Production;Property;Protein Biosynthesis;Proteins;recruit;Regulation;Research;Ribosomal Proteins;Ribosomal RNA;Ribosomes;RNA;RNA Processing;Role;self organization;Seminal;Signal Transduction;Solid Neoplasm;Specific qualifier value;Structure;Testing;Translations;Work;Yeasts;Zinc Fingers

PROJECT_TITLE: Uncovering novel players in nucleolar organization and function

STUDY_SECTION: NCSD

STUDY_SECTION_NAME: Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section[NCSD]


ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Peter Hunt, MD is a physician-scientist at the University of California San Francisco whose primary research program seeks to understand why people living with HIV have persistent inflammation despite treatment and an increased risk of diseases associated with the aging process. This career development award will provide him with enhanced training and protected time for mentoring junior investigators in patient-oriented research focused on these topics.

PI_NAMEs: HUNT, PETER W (contact)

PROGRAM_OFFICER_NAME: JANCI, ELIZABETH WONDERLICH

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adipose tissue;aging process;AIDS clinical trial group;Anti-Inflammatory Agents;antiretroviral therapy;Automobile Driving;Award;base;Blood Vessels;California;cardiometabolism;Cardiovascular system;career;career development;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;Cessation of life;Clinical;co-infection;cohort;collaboratory;Cytomegalovirus;Data;Dedications;Defect;Diabetes Mellitus;Disease;disorder risk;Educational workshop;Environment;Epithelial Cells;Etiology;Event;Exhibits;Foundations;Frequencies;Funding;gastrointestinal epithelium;Grant;Heart Diseases;high risk;HIV;HIV Infections;HIV Seropositivity;Immune;immune activation;immunodeficiency;Immunologics;Impairment;improved;indexing;Individual;Inflammation;Inflammatory;inflammatory marker;inhibitor;Insulin Resistance;interest;International;Intervention;K-Series Research Career Programs;Laboratories;Life Expectancy;lifestyle factors;Link;Malignant neoplasm of lung;Mediating;Medicine;Mentored Research Scientist Development Award;Mentors;Mentorship;microbial;Mid-Career Clinical Scientist Award (K24);mid-career faculty;Modernization;Morbidity - disease rate;mortality;multidisciplinary;Non-Insulin-Dependent Diabetes Mellitus;Organ;Pathway interactions;patient oriented research;Peer Review;Peptides;Persons;Phase;Physicians;Placebos;Population;Productivity;programs;Publications;Randomized, Controlled Trials;Recovery;Reporting;Research;Research Institute;Research Personnel;Research Training;Risk;Role;San Francisco;Science;Scientist;Secure;Series;skills;skills training;Smoking;Substance Use Disorder;systemic inflammatory response;T cell infiltration;T-Cell Activation;T-Lymphocyte;Time;TNF gene;Training;Training Activity;Training Programs;Universities;Valganciclovir;Vascular Diseases;Vascular Endothelium;Viral

PROJECT_TITLE: Persistent Functional Immune Defects in Treated HIV Infection

STUDY_SECTION: AIDS

STUDY_SECTION_NAME: Acquired Immunodeficiency Syndrome Research Study Section[AIDS]


NIH_SPENDING_CATS: Bioengineering;Cancer

ORG_DEPT: PHARMACOLOGY

PHR: Project Narrative To behave properly cells must integrate information coming from many extracellular stimuli. Cells accomplish this by forming transient complexes of multiple proteins, and causing these proteins to change their shapes and surface charges. We are developing new techniques to make this process visible, so we can study its role in immune cell function, cancer metastasis and basic cellular mechanisms.

PI_NAMEs: HAHN, KLAUS M. (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Active Sites;Adhesions;Behavior;Binding Sites;Biological Models;Biosensor;Blood Vessels;cancer cell;Cell Physiology;Cells;Cellular biology;Charge;Chemicals;Collagen;Complex;Computer Models;Cytoskeleton;Data;Elements;Engineering;Event;extracellular;Feedback;Frequencies;Frustration;Geometry;Image Analysis;Immune;in vivo;Individual;Kinetics;Light;Macrophage;mathematical model;mechanical force;Mechanical Stress;Methods;Microscopy;Molecular Conformation;multiplexed imaging;Neoplasm Metastasis;novel;novel strategies;organizational structure;Pattern;Phagocytes;Phagocytosis;Process;Proteins;quantitative imaging;Regulation;Reproducibility;Role;Shapes;Signal Transduction;Signaling Protein;small molecule;spatiotemporal;Stimulus;Stretching;Surface;Techniques;Time;tool;Variant;Visualization

PROJECT_TITLE: Dissecting signaling in vivo via precise control and visualization of protein activity

STUDY_SECTION: MRAB

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: DENVER

ORG_NAME: NATIONAL JEWISH HEALTH

ORG_STATE: CO

PHR: PROJECT NARRATIVE: Although treatment with immune checkpoint inhibitors (CPIs) has significantly improved outcomes for patients with cancer, CPIs are associated with a diverse spectrum of immune-related adverse events, the majority of which are skin related (ircAEs), which may result in CPI dose interruption or discontinuation. The overall objective of our current grant application is to identify pathways to mitigate ircAEs associated with cancer immunotherapy. Elucidation of the diverse mechanisms leading to ircAEs will result in actionable approaches for their management and improve cancer therapy.

PI_NAMEs: KERN, JEFFREY A;LACOUTURE, MARIO ;LEUNG, DONALD YM (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Adrenal Cortex Hormones;Adverse event;Affect;anti-CTLA4;Anti-Inflammatory Agents;anti-PD-L1;Applications Grants;Autoimmune;autoinflammatory;biobank;Biological;Biological Assay;Biological Markers;Biological Products;Blood;cancer immunotherapy;cancer therapy;Clinical;clinical phenotype;Cutaneous;cytokine;Cytokine Activation;Dermatologic;Development;Dose;Early identification;Endocannabinoids;Event;filaggrin;Glucocorticoid Receptor;glucocorticoid receptor alpha;Goals;Guidelines;Homing;Immune;Immune checkpoint inhibitor;Immune response;Immune Targeting;Immune Tolerance;immune-related adverse events;immunoreaction;improved;improved outcome;In Vitro;Inflammatory;Interleukin-13;Interleukin-4;Interruption;Intervention;Knowledge;Lead;Leukotrienes;Link;lipidome;Lipids;Maintenance;Malignant Neoplasms;novel therapeutic intervention;Organ;Pathogenicity;Pathway interactions;Patient-Focused Outcomes;Patients;Peripheral Blood Mononuclear Cell;Phenotype;Plasma;predicting response;Prevention;prospective;Prostaglandins;Reaction;Recommendation;Registries;Repression;Resolution;response;Role;Sampling;Signal Pathway;Signal Transduction;Skin;skin barrier;Skin Manifestations;Steroids;T-Lymphocyte;targeted treatment;Testing;TNF gene;Toxic effect;translational approach;translational immunology;Urine

PROJECT_TITLE: Identification of  pathways to mitigate Immune-Related Adverse Events with Cancer Immunotherapy


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Clinical Research;Emergency Care;Genetics;Neurosciences;Stroke

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE: Quick and confident recognition of stroke at initial clinician contact increases the odds of successful treatment and positive outcome. The proposed clinical study aims to determine whether the detection of molecules originating from damaged brain tissue in the blood can indicate if a stroke is occurring in patients who have neurological symptoms. If successful, the work will lay the immediate groundwork for the development of rapid blood-based diagnostic tests that could be used to aid in the recognition of stroke in emergency medicine settings.

PI_NAMEs: O'CONNELL, GRANT C (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Accident and Emergency department;Address;Admission activity;Ambulances;amplification detection;Area;Back;Biological Assay;Biological Markers;Blood;Blood specimen;Blood Tests;Blood Volume;Brain;Brain hemorrhage;Brain Injuries;brain tissue;Caring;Cause of Death;Cell Differentiation process;Cells;cerebrovascular;circular RNA;Clinical;Clinical Research;cohort;Country;Custom;Data;Detection;Development;Diagnosis;Diagnostic;Diagnostic Specificity;Diagnostic tests;diagnostic tool;digital;Emergency Medicine;Exhibits;Family;Foundations;Hospitalization;Immunoassay;improved;Informatics;innovation;interest;Intervention;Investigation;Ischemic Stroke;isothermal amplification;Laboratories;Laboratory Research;Lifelong disability;Measures;Mediating;Methods;Modeling;Molecular;Molecular Biology;Morbidity - disease rate;mortality;Myocardial Infarction;Nature;Nervous System Disorder;Nervous System Trauma;neural;Neurologic Symptoms;Neurons;novel;Nucleic Acids;Organ;Outcome;Patient-Focused Outcomes;Patients;Performance;point of care;Process;Proteins;Quantitative Reverse Transcriptase PCR;random forest;rapid detection;Resistance;Ribonucleases;RNA;Sampling;Screening procedure;Sensitivity and Specificity;Serum;Source;Stroke;stroke patient;stroke-like outcome;Surrogate Markers;Symptoms;tau Proteins;Techniques;Testing;Tissues;Transcript;Triage;Troponin;UCHL1 gene;United States;Untranslated RNA;Variant;Work

PROJECT_TITLE: Investigation of brain-originating circRNAs as targets in blood-based stroke triage diagnostics

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


NIH_SPENDING_CATS: Cancer;Climate-Related Exposures and Conditions;Clinical Research;Cost Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Social Determinants of Health

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative  Our proposal will be focused on increasing capacity in the Middle East and North Africa in environmental health research and especially with regards to climate change. There is a major gap in research capacity in this field despite the region is already suffering the health consequences of climate change in terms of increased frequency of heatwaves, desert dust storms, and drought and low frequency of precipitation. The hub will create the platform to expand and sustain this focus as the state-of-art go to entity in the region to help the populations and decisions makers address the climate change health impacts.

PI_NAMEs: ABDULLA, FAYEZ AHMAD;AL-DELAIMY, WAEL K (contact)

PROJECT_TERMS: Address;Air Pollution;Area;Awareness;California;Climate;climate change;climate impact;climate-related health;Collaborations;Communicable Diseases;Communities;Cost Effectiveness Analysis;dissemination science;Doctor of Philosophy;Droughts;Dust;Economic Models;Educational workshop;Environmental Health;Event;extreme weather;Floods;Grant;Health;Health Benefit;Health Policy;Health Sciences;Heat Waves;Human;implementation science;Individual;Institution;institutional capacity;Intervention;Jordan;Lebanon;Link;Local Government;Mental disorders;Mentors;Middle East;Morocco;Northern Africa;Planet Earth;Policies;Policy Maker;Pollution;Precipitation;programs;Research;Research Training;Risk;Science;symposium;Technology;Training;Training Programs;Universities;vector;virtual;Visit;water quality;webinar;Wildfire;Work

PROJECT_TITLE: 2/2 GeoHealth Hub for Climate Change and Health in the Middle East and North Africa-U.S.


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Dietary Supplements

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: CHEMISTRY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE Radical S-adenosylmethionine enzymes, which are iron-sulfur-dependent proteins, catalyze myriad cellular reactions using free radical mechanisms, including the methylation of small molecules, DNA, RNA, proteins, and lipids. Many of these methylation reactions are involved in numerous processes important in human health, such as antibiotic biosynthesis and resistance, and the biosynthesis of essential cellular molecules.

PI_NAMEs: BOOKER, SQUIRE J. (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Mechanisms of Iron-Sulfur Dependent Reactions


ADMINISTERING_IC: DP

IC_NAME: NATIONAL CENTER FOR CHRONIC DISEASE PREVENTION AND HEALTH PROMOTION

ORG_CITY: MADISON

ORG_NAME: WISCONSIN DEPARTMENT OF HEALTH SERVICES

ORG_STATE: WI

PHR: Project Narrative The Wisconsin Department of Health Services (DHS), Division of Public Health (DPH) is applying to the Centers for Disease Control and Prevention for the Pregnancy Risk Assessment Monitoring System (PRAMS) Funding Opportunity Announcement Number: RFA-DP-21-001, Component A: Core Funding. PRAMS is an ongoing survey of mothers who recently had a live birth, conducted by the CDC and local agencies. This fourth cycle of funding will allow Wisconsin PRAMS to continue for the project period May 1, 2016 – April 30, 2021. PRAMS will survey mothers asking about maternal behaviors before, during, and after pregnancy.

PI_NAMEs: PERZAN, MIREILLE  (contact)

PROJECT_TITLE: RFA-DP-21-001 DP006598 Wisconsin Pregnancy Risk Assessment Monitoring Systems (PRAMS): Understanding Racial Disparities


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE  Since the ancient Greeks, sulfur containing molecules have been used in a medicinal context, and they continue to represent a large portion of new FDA approvals. Despite their prevalence, existing methods to prepare C-S bonds lack the chemo- and enantioselectivity that is necessary in targeted pharmaceutical synthesis. This proposal describes the regio- and enantioselective preparation of thioethers from feedstock olefins using copper(I) hydride catalysis in conjunction with a sulfenamide-based sulfur transfer reagent.

PI_NAMEs: STRAUSS, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TITLE: Enantioselective Thioetherification of Olefins Guided by CuH Catalysis


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Brain Disorders;Clinical Research;Substance Misuse

ORG_DEPT: ADMINISTRATION

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE: Many individuals with alcohol use disorder (AUD) receive no treatment, including evidence-based medications. Prior studies of AUD medication use primarily relied on claims data and so could not account for whether someone received a prescription in the first place. This study, using linked electronic health record data on medication orders and claims data (combined with qualitative methods), will allow more precise identification of where individuals fall off the path of AUD medication use, and the outcomes associated with different treatment trajectories.

PI_NAMEs: HODGKIN, DOMINIC ;HUSKAMP, HAIDEN A. (contact)

PROGRAM_OFFICER_NAME: KWAKO, LAURA ELIZABETH

PROJECT_TERMS: acamprosate;Accidental Injury;Acute;addiction;Address;Adherence;Admission activity;alcohol use disorder;Alcohols;Caring;Characteristics;Chronic;Clinical;clinical training;clinically relevant;Data;Data Set;Deductibles;demographics;design;Diagnosis;Diffuse;Disulfiram;Drug Prescriptions;Education;Effectiveness;efficacious treatment;Electronic Health Record;Emergency department visit;Enzymes;evidence base;experience;Failure;falls;Familiarity;Fill-It;Future;health plan;Household;improved;Income;indexing;Individual;Injury;insight;Insurance;Insurance Carriers;Intervention;Interview;Laboratory Finding;Lead;Link;Liver;Liver Cirrhosis;Liver diseases;male;Measures;Medical;medication compliance;Medicine;men;Mental disorders;Methods;Morbidity - disease rate;mortality;Naltrexone;Outcome;Outpatients;Patients;Perception;Persons;Pharmaceutical Preparations;Pharmacotherapy;Physicians;Play;Policies;Policy Maker;Population;Practice Management;practice setting;preference;primary care provider;Process;Provider;provider factors;Psychiatrist;Qualitative Methods;Readiness;Relapse;Reporting;Research;Role;screening, brief intervention, referral, and treatment;Services;social stigma;Specialist;Structure;therapy design;Time;Toxicology;uptake;Visit;Woman;Writing

PROJECT_TITLE: Medications for Alcohol Use Disorder:  Unfilled Prescriptions and Treatment Trajectories

STUDY_SECTION: AA

STUDY_SECTION_NAME: Clinical, Treatment and Health Services Research Study Section[AA-3]


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

ORG_CITY: ATLANTA

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

ORG_STATE: GA

PHR: Copper is an essential trace nutrient critical to human health. A significant number of diseases, including Wilson disease, Menkes syndrome, or Alzheimer’s disease, are caused by impaired copper transport and regulation. The goal of this project is to create molecular tools that will enable the elucidation of copper trafficking pathways in these diseases, and thus support the development of novel diagnostic and therapeutic approaches that will aid in combating copper related human diseases.

PI_NAMEs: FAHRNI, CHRISTOPH J (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Alzheimer's Disease;Amines;Applications Grants;Biological Process;cofactor;combat;Complex;Copper;Development;Disease;Drug Metabolic Detoxication;Environment;Failure;Goals;Health;Hepatolenticular Degeneration;Homeostasis;Human;human disease;Hydroxyl Radical;Impairment;Iron;Knowledge;Ligands;Membrane Transport Proteins;Menkes Kinky Hair Syndrome;Metalloproteins;Methods;Molecular;Molecular Chaperones;Neurodegenerative Disorders;novel diagnostics;novel therapeutic intervention;novel therapeutics;Pathologic;Pathway interactions;Physiological;Production;Proteins;Proteome;Reactive Oxygen Species;Regulation;Research Personnel;Respiration;Superoxides;tool;Toxic effect;Trace Elements Nutrition;trafficking;transcription factor;uptake

PROJECT_TITLE: Molecular Tools to Illuminate Copper Transport and Homeostasis

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


ORG_CITY: DETROIT

ORG_DEPT: BIOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Project narrative – public health relevance  Perturbation of inositol metabolism is associated with pathologies as diverse as psychiatric and neurological illnesses, myopathies, cancer, and diabetes. The proposed studies will lead to the first molecular model of regulation of inositol synthesis in mammalian cells and demonstrate how inositol deprivation affects mitochondrial function and the cellular stress response. The identification of specific pathways that are perturbed as a result of inositol deprivation will provide insights into the tumor-suppressive effects of upregulating inositol synthesis and may suggest candidates for new mood stabilizing inositol-depleting drugs for the treatment of bipolar disorder.

PI_NAMEs: GREENBERG, MIRIAM L (contact)

PROJECT_TERMS: 3-Methylglutaconic aciduria type 2;Affect;Anabolism;Binding;Biochemical;biological adaptation to stress;Bipolar Disorder;Cell Physiology;Cells;Cellular Metabolic Process;Cellular Stress;Ceramides;Code;deprivation;Diabetes Mellitus;drug action;Drug usage;Enzymes;Eukaryotic Cell;Exhibits;Gene Expression;Genes;Genetic Transcription;Homeostasis;Human;Human Cell Line;Inositol;inositol hexakisphosphate kinase;Inositol Metabolism Pathway;insight;Knock-out;Knowledge;Light;Lipids;Malignant Neoplasms;Mammalian Cell;Mediating;Mental disorders;Mitochondria;Mitochondrial Diseases;mitochondrial dysfunction;molecular modeling;monolysocardiolipin;Moods;myoinositol;Myopathy;Neurologic;Nuclear;Pathology;Pathway interactions;Pharmaceutical Preparations;Pharmacotherapy;Phosphatidic Acid;Play;Population;promoter;Proteins;public health relevance;Regulation;Repression;Research;response;Role;Signal Transduction;Starvation;Stress;Testing;Therapeutic;tumor

PROJECT_TITLE: Regulation of inositol biosynthesis and consequences of inositol depletion


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Bipolar Disorder;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Serious Mental Illness;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_CITY: AUSTIN

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: This application describes a research plan for a longitudinal study in bipolar disorder and typical developing young adults aimed at capturing biological risk factors that are predictive of alcohol use disorders. The goals of the research are to investigate longitudinal changes in subjective response to alcohol, placebo response, corticolimbic neural trajectories, stress, and emergence of alcohol misuse and problems during the young adult epoch and interactions with bipolar disorder. Findings may inform prediction models of alcohol use disorders.

PI_NAMEs: LIPPARD, ELIZABETH THOMAS COX (contact)

PROGRAM_OFFICER_NAME: EGLI, MARK

PROJECT_TERMS: Acute;acute stress;Address;Adolescence;Affect;aged;Alcohol abuse;Alcohol consumption;alcohol effect;alcohol misuse;alcohol response;alcohol risk;alcohol sensitivity;alcohol use disorder;Alcohols;Amygdaloid structure;Back;Biological;Bipolar Disorder;Child Abuse and Neglect;Clinical;clinical phenotype;clinical prognosis;Clinical Research;Cognitive deficits;comorbidity;Corpus striatum structure;Coupling;Data;Development;Diagnosis;Disease;early life stress;Enrollment;Exclusion;Exposure to;Female;Fibrinogen;follow-up;functional loss;functional MRI scan;Funding;General Population;Goals;gray matter;Human;improved;improved outcome;Impulsivity;Individual;Insula of Reil;interest;Intervention;Longitudinal Studies;Mentored Research Scientist Development Award;Methodology;Modeling;Moods;multidisciplinary;multimodal neuroimaging;neural;neurodevelopment;neuroimaging;neurophysiology;novel;Outcome;participant enrollment;Placebo Effect;Placebos;Population;preclinical study;Predictive Factor;predictive modeling;Prevention;Procedures;prospective;Reporting;Research;Research Personnel;Research Project Grants;response;reward processing;Risk;Risk Factors;Risk Marker;Risk Taking;Role;Stress;stressor;Structural Models;Structure;Substance Use Disorder;suicide rate;Symptoms;Testing;Time;Translating;Variant;white matter;Work;young adult;Youth

PROJECT_TITLE: Biological Risk Factors for the Prospective Development of Alcohol Use Disorders in Young Adults with Bipolar Disorder and Typically Developing Young Adults

STUDY_SECTION: NPAS

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Eye Disease and Disorders of Vision;Genetics;Human Genome;Rare Diseases

ORG_DEPT: DERMATOLOGY

PHR: Project Narrative Uveal melanoma is a devastating eye cancer that is untreatable once it metastasizes. We have identified major genetic alterations and will now use long read single molecule sequencing to expand our findings. These changes will be modeled in the fly model system to identify novel therapeutic candidates.

PI_NAMEs: BOWCOCK, ANNE MARY (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Abnormal Karyotype;Address;Age;Alternative Splicing;Antineoplastic Agents;Applications Grants;Automobile Driving;BAP1 gene;Biological Models;Biological Sciences;Blindness;cancer genome;Cancer Model;Candidate Disease Gene;Cell Line;Cessation of life;Characteristics;chromatin modification;Chromatin Remodeling Factor;chromosome 1p loss;Chromosome 3;chromosome 8q gain;Chromosome abnormality;Chromosomes;Classification;Clinical;Competence;Complement;cysteinyl leukotriene receptor 2;Detection;Development;Diagnosis;DNA Sequence Rearrangement;DNA sequencing;driver mutation;Drosophila genus;effective therapy;epigenomics;Epithelium;Event;Exhibits;exome;experimental study;Eye;Eye Neoplasms;fly;Future;G-Protein-Coupled Receptors;Gene Expression Profile;Gene Fusion;Generations;Genes;Genetic;Genome;Genomic DNA;Genomics;GNAQ gene;Grant;Growth;GTP-Binding Proteins;guanine nucleotide binding protein;high risk;Human;Immune checkpoint inhibitor;insight;Introns;Length;loss of function;loss of function mutation;Loss of Heterozygosity;malignant neoplasm of eye;Malignant Neoplasms;Maps;MEKs;melanocyte;Melanoma;Modeling;Molecular;monolayer;Mutation;Neoplasm Metastasis;Nonmetastatic;novel therapeutics;Ocular Melanoma;Oncogenic;Orthologous Gene;Pathogenicity;Pathway interactions;Patients;Phenotype;polypeptide;preferentially expressed antigen in melanoma;Primary Neoplasm;Prognosis;Protein Isoforms;Recurrence;Research;Resolution;Risk;RNA;Signal Transduction;single molecule;Site;Solid Neoplasm;Somatic Mutation;success;System;Systemic Therapy;Testing;therapeutic candidate;Tissues;transcriptome sequencing;Transgenic Organisms;tumor;tumor diagnosis;Up-Regulation;Uveal Melanoma;Variant;Wing;Work

PROJECT_TITLE: The Genetics of Ocular Melanoma


NIH_SPENDING_CATS: Hematology;Immunotherapy;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: BALTIMORE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Project Narrative Neurotransmitters and hormones serve as a link between the nervous and immune systems. This study will determine the mechanisms by which the β2-adrenergic signaling pathway regulates immune cell development and reconstitution, and its impact on graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT).

PI_NAMEs: CAO, XUEFANG  (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: adaptive immunity;Adrenal Medulla;Adrenergic Agents;Adrenergic Agonists;Allogenic;antagonist;Autoimmune Diseases;beta-2 Adrenergic Receptors;Biological Assay;blood treatment;Bone Marrow;Bone Marrow Cells;Cell Count;Cell Differentiation process;Cell Physiology;cell type;Cells;Clinical Trials;Collaborations;Complex;Cre-LoxP;CSF1R gene;Cytometry;Dendritic Cells;Development;Disease;Epinephrine;Flow Cytometry;Functional disorder;Genes;Genetic Polymorphism;Genus Hippocampus;germ free condition;graft vs host disease;Hematological Disease;Hematopoietic Neoplasms;Hematopoietic Stem Cell Transplantation;Homeostasis;Hormones;Host Defense;Human;Immune;immune reconstitution;Immune response;Immune signaling;Immune system;Immune System Diseases;Immunotherapy;improved;Intervention;Knock-out;Ligands;Link;Macrophage;Macrophage Colony-Stimulating Factor;Mature T-Lymphocyte;Metabolic;metabolic fitness;migration;Modeling;Molecular;monocyte;mouse model;Mus;Myelogenous;myeloid cell development;Myeloid Cells;Natural Immunity;Nervous System;Neuroimmune;Neurons;Neurotransmitters;Norepinephrine;Organ;Outcome;Pathogenesis;Patients;Peripheral;peripheral lymphoid organ;pharmacologic;Phenotype;Play;Proliferating;Publishing;Receptor Signaling;reconstitution;Regulation;Reporting;Research;restraint;Role;Signal Pathway;Signal Transduction;Sympathetic Nervous System;System;T cell differentiation;T cell reconstitution;T cell response;T-Cell Depletion;T-Cell Development;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Therapeutic;Thymus Gland;transcriptome sequencing;transcriptomics;translational potential;Transplantation

PROJECT_TITLE: Beta-2 adrenergic signaling in immune homeostasis and reconstitution

STUDY_SECTION: TTT

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


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Prevention

ORG_CITY: IOWA CITY

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE Neurodegenerative disorders are a significant public health and economic problem affecting about 450 million people worldwide are the leading cause of disability and ill-health according to world health organization. The main objective of the proposal is the development, validation and translation of a non-invasive diffusion MRI assay, that enable efficient encoding of diffusion parameter space to characterize the neurodegenerative processes that drive the progression of neurodegeneration. We validate the framework in a cohort of Huntington's disease, with the prospect of extending these studies to understand the neurodegenerative cascade in the entire class of neurodegenerative diseases, including Parkinson's and Alzheimer's.

PI_NAMEs: MANI, MERRY  (contact)

PROGRAM_OFFICER_NAME: BARRY, ROBERT LEO II

PROJECT_TERMS: 3-Dimensional;Acceleration;advanced disease;Affect;Algorithms;Alzheimer's Disease;Animal Model;Architecture;axonal degeneration;Biological Assay;Biological Markers;biophysical model;Brain;brain circuitry;Calibration;Cause of Death;Clinical Research;clinical translation;cohort;Compensation;Coupled;Cross-Sectional Studies;Data;Dedications;deep learning;deep learning model;Demyelinations;design;Development;Diffusion;Diffusion Magnetic Resonance Imaging;Dimensions;disability;Disadvantaged;Disease;Early Diagnosis;Economics;effectiveness evaluation;Effectiveness of Interventions;Ensure;Fiber;Health;healthy volunteer;high resolution imaging;Human;Huntington Disease;Image;image reconstruction;improved;in vivo;Intervention;Iron;Joints;Learning Module;Link;Machine Learning;Magnetic Resonance Imaging;Malignant Neoplasms;Maps;Measurement;Measures;Methods;millimeter;Modeling;Morphologic artifacts;Motion;multimodality;Myelin;Nerve Degeneration;neural network;Neurodegenerative Disorders;neuroinflammation;neuron loss;Neurons;noninvasive brain stimulation;novel;Outcome;Parkinson Disease;Pattern;Persons;Pharmaceutical Preparations;Phase;physical property;Physics;Play;Process;Property;Protocols documentation;Public Health;reconstruction;Recovery;Resolution;Sampling;Self Correction;Signal Transduction;Specificity;Structural Models;Structure;Study models;Symptoms;targeted treatment;Techniques;Technology;Time;Tissue Model;Tissues;Translations;Validation;Water;white matter;Work;World Health Organization

PROJECT_TITLE: Fast Multi-dimensional Diffusion MRI with Sparse Sampling and Model-based Deep Learning Reconstruction

STUDY_SECTION: EITN

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


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: CHARLESTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Compulsive drug seeking despite negative consequences is a hallmark of opioid addiction, and such behaviors are associated with abnormal activity patterns in the prefrontal cortex. Characterizing the precise neuronal circuits in prefrontal cortex that contribute to drug seeking is therefore critical for developing effective treatment strategies that can normalize brain activity and reduce relapse vulnerability. Here, we use cutting edge neuro- technologies to determine the function of precisely-defined prefrontal circuits for cue-induced heroin seeking.

PI_NAMEs: OTIS, JAMES M (contact)

PROGRAM_OFFICER_NAME: TSAI, SHANG-YI ANNE

PROJECT_TERMS: Axon;Behavior;beta-adrenergic receptor;Brain;Brain region;Calcium;calcium indicator;Cells;Characteristics;Complex;Cue-induced relapse;Cues;Data;Development;drug reward;drug seeking behavior;Drug usage;effective therapy;Elements;excitatory neuron;experimental study;Extinction;Foundations;Future;Gene Expression;Genetic;Heroin;heroin use;Human;Image;Impairment;Individual;Jaw;Light;Literature;locus ceruleus structure;Measures;Mus;Neuromodulator;neuronal circuitry;Neurons;neurotechnology;noradrenergic;Norepinephrine;novel;Opiate Addiction;Opsin;optogenetics;Output;Patients;Pattern;Pharmaceutical Preparations;Population;Prefrontal Cortex;Publications;redshift;Relapse;Resolution;Rewards;Rodent;Self Administration;Stimulus;Structure;Substance Use Disorder;Sucrose;Testing;therapy development;Time;treatment strategy;two-photon

PROJECT_TITLE: The influence of noradrenergic circuitry on prefrontal neuronal ensemble dynamics and cue-induced heroin seeking

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Complementary and Integrative Health;Congenital Structural Anomalies;Dietary Supplements;Kidney Disease;Nutrition;Pediatric;Polycystic Kidney Disease;Prevention

ORG_CITY: SANTA BARBARA

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: Project Narrative We have discovered that the metabolic state of ketosis profoundly inhibits - and even reverses - the progression of polycystic kidney disease (PKD) in animal models. Inducing ketosis with dietary interventions or mimicking it by administration of the natural ketone body β-hydroxybutyrate (BHB) all proved highly effective in inhibiting renal cyst proliferation and ?brosis. Here, we propose to identify the most effective treatments and study the underlying mechanisms in order to be able to design a future clinical trial to test the ef?cacy of dietary interventions and/or treatment with BHB, an inexpensive and safe compound that is FDA-classi?ed as a dietary supplement.

PI_NAMEs: WEIMBS, THOMAS  (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Acceleration;Adherence;Affect;Animal Model;Autosomal Dominant Polycystic Kidney;beta-Hydroxybutyrate;Cells;Classification;clinical practice;clinical translation;Clinical Trials;cost;Cyclic AMP;Cyst;Cystic kidney;Data;Defect;design;Dietary Intervention;dietary supplements;disease model;Disease Progression;Dose;drinking water;Eating;effective therapy;Epithelial Cells;experimental study;Family Felidae;Fatty acid glycerol esters;Fatty Acids;FDA approved;Fibrosis;Formulation;Future;G-Protein-Coupled Receptors;Genetic Diseases;Glucose;Goals;Growth;high reward;human disease;Intervention;Investigation;ketogenic diet;ketogentic;Ketone Bodies;Ketones;Ketosis;Kidney Diseases;Kidney Failure;Knock-out;Lead;Metabolic;Metabolic Diseases;Modeling;Molecular;mouse model;mTOR inhibition;Mus;Myofibroblast;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Physiological;Polycystic Kidney Diseases;prevent;Proliferating;Quality of life;Rattus;receptor;Regimen;Reporting;response;Risk;Rodent;Rodent Model;side effect;Signal Transduction;Sodium Chloride;Starvation;Supplementation;Testing;Time;Time-restricted feeding;Toxic effect;Work

PROJECT_TITLE: Ketosis as a therapy for polycystic kidney disease

STUDY_SECTION: KMBD

STUDY_SECTION_NAME: Kidney Molecular Biology and Genitourinary Organ Development[KMBD]


ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative I discovered that CDK13, a gene expression kinase, is mutated in patient melanomas and is required to activate a nuclear RNA surveillance pathway. When CDK13 is mutated, prematurely terminated RNAs accumulate and are translated, resulting in more aggressive melanoma. Having recently identified recurrent mutations in RNA surveillance pathway members in cancer, I propose to determine how CDK13 mutations and loss of nuclear RNA surveillance members cause more aggressive melanoma.

PI_NAMEs: INSCO, MEGAN LEIGH (contact)

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Affect;Aggressive behavior;Area;Award;Binding;Biological Assay;Boston;Cancer Biology;Cell Culture System;Cell Proliferation;Cells;Cellular Stress;Clinical;Collaborations;Complex;Cyclin-Dependent Kinases;Cyclins;Cytoplasm;Dana-Farber Cancer Institute;Data;Dissection;Dominant-Negative Mutation;Down-Regulation;Drug Targeting;Endoplasmic Reticulum;Environment;Epigenetic Process;exosome;Failure;Family;Gene Expression;Genes;Genetic;Genetic Transcription;Grant;Growth;Heat shock proteins;Hematologist;Human;Image;Immunotherapy;In Vitro;in vivo;inhibitor therapy;Investments;kinase inhibitor;Laboratories;Leadership;Learning;Lysosomes;Mainstreaming;Malignant Neoplasms;Measures;medical schools;melanocyte;Melanoma;Melanoma Cell;Melanoma patient;member;Mentors;Metastatic Melanoma;model organism;Modeling;Molecular;mutant;Mutate;Mutation;Nuclear;Nuclear RNA;Oncogenic;Oncologist;Pathway interactions;Patients;Pediatric Hospitals;Peptides;Phenotype;Phosphorylation;Phosphotransferases;Phylogenetic Analysis;Pigments;premature;Process;Prognosis;Progressive Disease;Proliferating;protein expression;Protein Truncation;Proteins;Proteomics;Publishing;Recommendation;Recurrence;Refractory;Reporter;Research;Research Personnel;Resistance;RNA;Scientist;skills;Skin Cancer;Stress;stress granule;System;Techniques;Testing;Therapeutic;Time;Training;Transcription Elongation;transcriptome sequencing;transcriptomics;Translating;Translations;tumor;tumorigenesis;Western Blotting;Work;Zebrafish

PROJECT_TITLE: Investigating Transcriptional Elongation and Nuclear RNA Surveillance in Melanoma

STUDY_SECTION: NCI

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


NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Neurosciences;Pediatric;Rare Diseases;Sickle Cell Disease

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Children with anemia, including sickle cell anemia, are at risk for not having enough oxygen for full brain growth and development. Upon conclusion of this study, we will have a greater understanding of the interaction of lower oxygen supply and brain development. Determining the age-dependence of vulnerability to low oxygen and the effect on brain development will allow us to personalize treatment strategies for children at high risk for neurodevelopmental brain injury.

PI_NAMEs: GUILLIAMS, KRISTIN  (contact)

PROGRAM_OFFICER_NAME: HARTMAN, ADAM L

PROJECT_TERMS: Adult;Affect;African American;Age;age related;age stratification;Anemia;Area;arteriole;Blood flow;Brain;brain dysfunction;Brain imaging;Brain Injuries;brain volume;Cell Death;Cell Physiology;cellular imaging;Cerebral Infarction;cerebrovascular reactivity;Cerebrum;Child;Childhood;Chronic;Clinical Treatment;cohort;cost;Coupled;Data;Data Set;Databases;Dependence;Development;Ensure;Evolution;experience;follow-up;Goals;gray matter;Growth;Growth and Development function;hemodynamics;Hemoglobin;high risk;hydroxyurea;Hypoxemia;Image;Imaging Techniques;impaired brain development;improved;Infarction;Injury;innovation;Intervention;Knowledge;Link;Magnetic Resonance Imaging;Measures;Metabolic;metabolic imaging;Metabolism;Modeling;Neurological outcome;Only Child;Oxygen;personalized medicine;Physiological;Population;Prevention therapy;Resolution;Risk;Role;sex;Sickle Cell;Sickle Cell Anemia;Signal Transduction;Stroke prevention;structural imaging;Technology;Thick;Thinness;Transfusion;treatment strategy;white matter

PROJECT_TITLE: The role of metabolic and hemodynamic reserve in age-related brain vulnerability in pediatric sickle cell anemia

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Microbiome

PHR: PROJECT NARRATIVE Generalized approaches for laryngopharyngeal reflux (LPR), a prevalent syndrome in which laryngeal symptoms are attributed to gastroesophageal reflux disease, have resulted in poor patient outcomes, inappropriate utilization of healthcare resources, and tremendous expenditure. Information from this biomarker targeted randomized sham-controlled clinical trial of the upper esophageal sphincter assist device will be analyzed using novel latent class and microbiomics methods in order to define a phenotype guided treatment approach for LPR and inform the mechanistic understanding of reflux associated oral microbiome changes as a source of chronic inflammation in LPR. These findings will ultimately contribute to developing modern practice paradigms for LPR in order to optimize patient care, as well as provide fundamental knowledge about mechanistic pathways and symptom generation in LPR.

PI_NAMEs: YADLAPATI, RENA HIREN (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: Accounting;Address;Adult;arm;authority;Bioinformatics;Biological Markers;California;career;career development;Caring;Chronic;Clinical;Clinical Data;Clinical Management;clinical translation;Clinical Trials;colorectal cancer screening;Communities;constriction;Controlled Clinical Trials;cost;Data;Deglutition Disorders;design;Devices;Diagnosis;Diagnostic;diagnostic biomarker;Diagnostic Procedure;Digestive System Disorders;Disease;Double-Blind Method;Dysphonia;electric impedance;Ensure;Environment;Esophageal Diseases;Esophagus;Expenditure;experience;Fluoroscopy;Future;Gastroesophageal reflux disease;Generations;Goals;Grant;gut microbiome;Health;Health Care Costs;health care service utilization;healthcare burden;improved;indexing;Inferior esophageal sphincter structure;Inflammation;Infrastructure;innovation;Institution;International;Knowledge;laryngopharyngeal reflux;Larynx;Manometry;Measures;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Metagenomics;Methods;microbial;microbiome;microbiome research;microbiome sequencing;Modernization;multidisciplinary;National Institute of Diabetes and Digestive and Kidney Diseases;novel;novel diagnostics;novel therapeutics;Observational Study;Operative Surgical Procedures;Oral;Oral Characters;oral microbial community;oral microbiome;Outcomes Research;Pathway interactions;Patient Care;Patient-Focused Outcomes;Patients;Pepsin A;Pharyngeal structure;Phenotype;Physicians;Physiological;Physiology;poor health outcome;primary outcome;Proton Pump Inhibitors;Randomized;Randomized, Controlled Trials;recruit;Reflux;Research;Research Design;research facility;Research Institute;Research Personnel;Research Training;Resources;response;Salivary;Scientist;Screening procedure;secondary outcome;Self-Help Devices;Seminal;Shotgun Sequencing;Signs and Symptoms;skill acquisition;skills;Source;supportive environment;Symptoms;Syndrome;targeted biomarker;Techniques;Testing;Therapeutic;tool;Training;Translational Research;Treatment outcome;treatment strategy;trial design;United States National Institutes of Health;Universities;Upper Esophageal Sphincter;validation studies;Visit;Voice Disorders;Work

PROJECT_TITLE: Mechanism Guided Therapy for Laryngopharyngeal Reflux

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative This project seeks to develop scalable long acting medicines for HIV-1 prevention. Our aims are to improve adherence to life saving medicines and reduce the likelihood of viral transmission.

PI_NAMEs: EDAGWA, BENSON ;GENDELMAN, HOWARD E (contact)

PROGRAM_OFFICER_NAME: PROTOPOPOVA, MARINA

PROJECT_TERMS: Adherence;Adverse event;AIDS prevention;Animal Model;Animals;Anti-Retroviral Agents;antiretroviral therapy;Area;bench to bedside;Biological Availability;Biological Models;biomaterial compatibility;CD4 Positive T Lymphocytes;Cell Count;Cells;Characteristics;chemical synthesis;Chemicals;Chemistry;Conscious;cost;Creativeness;Data;Data Set;design;Development;disease transmission;Dose;Drug Design;Drug Formulations;Drug Kinetics;drug modification;Drug or chemical Tissue Distribution;efficacy evaluation;emtricitabine;Esterification;Esters;expectation;Female;forging;Formulation;Freeze Drying;Frequencies;Funding;Future;Goals;Good Manufacturing Process;Half-Life;Health;Healthcare;Hematology;high risk;Histology;HIV Infections;HIV-1;Human;humanized mouse;Hydrolysis;Hydrophobicity;Immunologics;improved;Individual;Industry;Infection;Infrastructure;Injections;innovation;interdisciplinary approach;Interdisciplinary Study;Intramuscular Injections;Investigational New Drug Application;Laboratories;large scale production;Lead;Letters;Life;Link;Lipids;lipophilicity;Macaca mulatta;Macrophage;male;manufacture;manufacturing facility;Measures;Medicine;Metabolic;Modification;multidisciplinary;Mus;Names;nano;nanocrystal;nanoformulation;nanomedicine;Nebraska;novel;novel strategies;nucleoside monophosphate;Nucleotides;particle;Pathway interactions;Penetrance;Personal Satisfaction;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacologic Substance;Pharmacy (field);pill;Plasma;Powder dose form;pre-exposure prophylaxis;Preclinical Testing;prevent;Prevention;Process;Prodrugs;product development;Publications;Publishing;Quality Control;Rattus;Reproducibility;Research;Research Design;Research Personnel;Research Project Grants;Rest;Reticuloendothelial System;Rodent;Safety;scale up;Scheme;Science;Scientist;Sex Differences;Site;Specific qualifier value;Substance Use Disorder;surfactant;Suspensions;Tenofovir;Test Result;Testing;therapy design;Tissues;tool;Toxicology;translational study;transmission process;Treatment Protocols;United States Food and Drug Administration;Universities;uptake;Validation;Viral Load result;Viral reservoir;viral resistance;viral transmission;Virus;Virus Replication;Work

PROJECT_TITLE: LASER ART for PreP

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Inflammatory Bowel Disease

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Unchecked intestinal inflammation predisposes inflammatory bowel disease patients to colitis associated cancer (CAC). Delineating the epithelial-specific and immune pathways that contribute to CAC is critical to identifying genetic factors in patients that place them at increased risk for developing CAC. In this application, the candidate outlines a detailed scientific plan to mechanistically dissect the role of an intestinal epithelial repair protein, LINGO2, in control of colitis and its complications with the goal of unraveling the pathophysiology of CAC.

PI_NAMEs: BELLE, NICOLE MALONEY (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: 3-Dimensional;Abscess;adenoma;Affect;American;Azoxymethane;Biological Models;Biology;Bone Marrow;Carcinogens;Carcinoma;career development;cell type;Cells;Cellular biology;Chimera organism;Chronic;Colitis;colitis associated cancer;Colitis associated colorectal cancer;Colonic Neoplasms;comparison control;CRISPR/Cas technology;cytokine;Data;Defect;Development;dextran sulfate sodium induced colitis;Disease;disease model;Disease remission;disorder risk;EGFR inhibition;Environment;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Epithelial Cells;epithelial repair;Epithelium;experimental study;Exposure to;Faculty;Fistula;Foundations;Functional disorder;Funding;Genes;Genetic;genetic manipulation;Genetic Polymorphism;genome wide association study;Germ Lines;Goals;Growth;gut inflammation;Hematopoietic;Hemorrhagic colitis;Homeostasis;Human;IL6 gene;Immune;Immunology;In Vitro;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;innovation;Interleukin-6;intestinal barrier;intestinal epithelium;Intestines;Investigation;Kinetics;Knock-in;Knock-out;Knockout Mice;knowledge base;leucine-rich repeat protein;Malignant - descriptor;Malignant Neoplasms;member;Membrane;microbiota;Molecular;mouse model;Mucous Membrane;Mus;Mutant Strains Mice;Myelogenous;Myeloid Cells;novel;organoid transplantation;Organoids;overexpression;Pathway interactions;Patients;Pennsylvania;Phosphorylation;Predictive Factor;Predisposition;Production;Proliferating;Protein Family;Proteins;Publications;Publishing;receptor;Receptor-Interacting Protein;Regulation;Relapse;repaired;Research;response;Risk;Role;Severities;Signal Transduction;skills;small molecule;Sodium Dextran Sulfate;STAT3 gene;Susceptibility Gene;Techniques;tenure track;Testing;tool;Training;Transplantation;trefoil factor;tumor;tumor microenvironment;tumorigenic;United States National Institutes of Health;Universities;Up-Regulation

PROJECT_TITLE: Regulatory role for an epithelial repair protein, LINGO2, in colitis


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Depression;Genetics;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Substance Misuse

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: NARRATIVE: Individuals with alcohol use disorder (AUD) often suffer from depression, but the underlying neurobiological reasons for this co-occurrence are poorly defined. The current application will utilize a rodent model of AUD, similar to the human condition of alcohol dependence, to understand why individuals continue to drink despite negative affect during withdrawal - at the molecular, cellular, and behavioral levels. If our hypotheses bear out, this work will (1) identify the biochemical underpinning of the antidepressant/negative reinforcement properties of ethanol, (2) have broad implications to other complex brain disorders, and (3) help inform future applications with new druggable targets and reduce the burdens of illness and disability.

PI_NAMEs: RAAB-GRAHAM, KIMBERLY FRANCES (contact)

PROGRAM_OFFICER_NAME: LORANG-LEINS, DOMINIQUE

PROJECT_TERMS: Abstinence;Acute;Alcohol consumption;Alcohol dependence;alcohol effect;alcohol exposure;alcohol prevention;alcohol risk;alcohol use disorder;Alcohols;Anhedonia;Animals;antagonist;anti-depressive agents;antidepressant effect;Anxiety;anxiety-like behavior;Attention;Behavior;Behavioral;Binding;Binding Proteins;Biochemical;Biochemical Pathway;Bioinformatics;Brain Diseases;burden of illness;Chronic;Code;Communication;comorbidity;Complex;Data;Dendrites;depressive symptoms;detection assay;detection method;Development;disability;drinking;effective therapy;Electrophysiology (science);Emotional;Emotions;epidemiologic data;Ethanol;Ethanol dependence;experimental analysis;FDA approved;Female;FMR1 gene;Foundations;Future;Genetic Transcription;Genomic approach;Grant;Human;Immunoprecipitation;Individual;Influentials;Injections;Intervention;Intoxication;Knockout Mice;Knowledge;Laboratories;Libraries;Literature;Major Depressive Disorder;male;Mediating;Mental Depression;Mental Health;Messenger RNA;Methods;Modeling;Molecular;Motivation;Mus;N-Methylaspartate;National Institute on Alcohol Abuse and Alcoholism;negative affect;negative emotional state;Negative Reinforcements;Network-based;neural circuit;Neurobiology;Neurotransmitters;new therapeutic target;novel;Peptides;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phase;Phenotype;Play;Positive Reinforcements;pre-clinical;Pre-Clinical Model;Property;Protein Biosynthesis;protein expression;Proteins;Publishing;Repression;Research;Research Personnel;Rewards;RNA;RNA immunoprecipitation sequencing;RNA-Binding Proteins;Rodent Model;Role;Signal Pathway;Signal Transduction;Signaling Protein;Strategic Planning;Synapses;synaptogenesis;System;Techniques;Testing;transcriptome sequencing;Up-Regulation;Withdrawal;Work

PROJECT_TITLE: Biochemical Studies Underlying Acute Ethanol's Antidepressant-like effects during Withdrawal in a Preclinical Model of Ethanol Dependence

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative Mitochondria are central hubs of eukaryotic cells, playing essential roles not only for energy production but also in the regulation of metabolic pathways, innate immune responses and cell death/survival fate. Post-translational modifications (PTMs) of mitochondrial proteins are numerous and provide an important link between the regulation of mitochondrial functions and inter-organelle communication, and the availability of cellular metabolites. A better understanding of the role of mitonuclear communication pathways in modulating mitochondria functions through ubiquitination and ADP-ribosylation may provide important insights about metabolic regulatory strategies to be exploited therapeutically.

PI_NAMEs: PERISSI, VALENTINA  (contact)

PROJECT_TERMS: Address;ADP ribosylation;Area;biological adaptation to stress;Cell Death;Cell Differentiation process;Cell Nucleus;Communication;Complement;Dedications;Department of Defense;Disease;Enzymes;Eukaryotic Cell;Future;Gene Expression Regulation;Genetic Transcription;Genome Stability;Genomics;GPS2 gene;Homeostasis;inhibitor;Innate Immune Response;insight;Link;Malignant Breast Neoplasm;Mediating;Metabolic;Metabolic Control;Metabolic Pathway;Mitochondria;Mitochondrial Proteins;Molecular;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of General Medical Sciences;Natural Immunity;Nuclear;Nutrient availability;Obesity;Organelles;Oxidative Stress;Pathway interactions;Physiological;Play;Positioning Attribute;Post-Translational Protein Processing;Process;Production;programs;Regulation;Research;response;Role;Signal Transduction;Stress;targeted treatment;Therapeutic;Transferase;translational potential;Translational Regulation;Translations;Ubiquitin;Ubiquitination;Work

PROJECT_TITLE: Coordination of PAR and Ub signaling in mitochondria


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Neurosciences;Rehabilitation

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Severe bilateral loss of vestibular sensation – the inner ears' sense of balance – causes chronic dizziness, blurry vision during head movement, a constant need to exert conscious effort to do things that are normally automatic (like walking without wobbling or falling), and inability to drive or swim safely. In an already FDA- approved and actively recruiting first-in-human trial, we have recently shown that a vestibular implant that senses head motion and artificially stimulates the vestibular nerve – much like the way a cochlear implant helps treat people with severe hearing loss – helps to improve the signs and symptoms of bilateral vestibular loss caused by medicines that are sometimes toxic to the inner ear. The research project we now propose will (1) determine whether a vestibular implant can help the nearly 1 million adults disabled by bilateral vestibular loss that is idiopathic (has no identified cause); (2) assess the long-term safety and effectiveness of vestibular implants by supporting and tracking the performance of the pioneering subjects already implanted; (3) lay the groundwork for the first pivotal multicenter trial of vestibular implantation; (4) help ensure that vestibular implantation is available at centers in the United States; and (5) create a solid foundation from which vestibular implantation can grow, as did cochlear implantation, to become a routine and effective treatment, a robust and diverse field of clinical investigation, and a technology that opens new lines of scientific inquiry into how the inner ear and brain work together to help you see clearly, walk automatically, and focus your thoughts on where you are headed and why rather than on how to avoid falling on your way there.

PI_NAMEs: DELLA SANTINA, CHARLES C (contact)

PROGRAM_OFFICER_NAME: MILLER, ROGER

PROJECT_TERMS: 3-Dimensional;Action Potentials;Adult;Adverse event;Affect;Anatomy;Auditory;Authorization documentation;Bilateral;Brain;cell injury;Chronic;Clinical;clinical investigation;Cochlear implant procedure;Cochlear Implants;cognitive load;cohort;Compensation;Conscious;Consent;cost;Data;Databases;design;Devices;disability;disabled;Disabled Persons;Disabling;Dizziness;Ear;effective therapy;Effectiveness;effectiveness evaluation;efficacy evaluation;Electric Stimulation;Ensure;Equilibrium;Esthesia;Exclusion;Exhibits;experience;fall risk;falls;Feasibility Studies;first-in-human;follow-up;Foundations;Future;Gait;Grant;Hair Cells;Head;Head Movements;health related quality of life;Hearing;hearing impairment;Implant;implantation;improved;inclusion criteria;Individual;Institutional Review Boards;Laboratories;Labyrinth;Life;Longterm Follow-up;Measures;Medical Device;Medicine;Monitor;Motion;Multicenter Trials;National Institute on Deafness and Other Communication Disorders;Nerve;Noise;Operative Surgical Procedures;ototoxicity;Outcome;patient population;Patients;Performance;Persons;Posture;posture instability;power analysis;Procedures;programs;prospective;Prosthesis;Protocols documentation;Recruitment Activity;Regulation;Rehabilitation therapy;Reporting;Research;Research Design;Research Project Grants;response;Rotation;Running;Safety;Sample Size;Sampling;Scientific Inquiry;Semicircular canal structure;Signs and Symptoms;Solid;standard of care;Stimulus;Study Subject;Swimming;System;Technology;Testing;Therapeutic;Thinking;United States;United States Food and Drug Administration;Vestibular loss;Vestibular Nerve;vestibular system;vestibulo-ocular reflex;Vision;volunteer;Walking;Work

PROJECT_TITLE: Vestibular Implantation to Treat Adult-Onset Bilateral Vestibular Hypofunction


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Hematology;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PUBLIC HEALTH STATEMENT Protection from leukemia relapse in the central nervous system (CNS) is crucial to long-term survival and quality of life for leukemia patients. This proposal will define how the CNS protects leukemia cells from chemotherapy and test new therapeutic strategies to target leukemia cells in the CNS.

PI_NAMEs: GORDON, PETER M (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Acute Lymphocytic Leukemia;Adhesions;AMD3100;antagonist;Antibodies;Apoptosis;Apoptotic;Attenuated;Biological Assay;Biological Models;Biology;Blood;Blood - brain barrier anatomy;Bone Marrow;Cell Adhesion;Cell Adhesion Molecules;Cell Communication;Cell Cycle;Cell Cycle Progression;Cell Cycle Regulation;Cell Line;Cell Surface Proteins;Cell Survival;Cells;Central Nervous System;Central Nervous System Leukemia;Cerebrospinal Fluid;Chemoresistance;chemotherapy;Child;Clinic;clinical translation;Clinical Trials;Coculture Techniques;CXCR4 gene;Cytarabine;Data;Equilibrium;Exhibits;FDA approved;Genetic;Hematopoietic stem cells;Homo;improved;In Vitro;in vivo;in vivo evaluation;in vivo Model;insight;knock-down;Knowledge;leukemia;leukemia relapse;leukemia treatment;Leukemic Cell;Link;Mediating;Meningeal;Meninges;Molecular;Morbidity - disease rate;Mus;new therapeutic target;novel;novel strategies;novel therapeutic intervention;Outcome;Pathway interactions;Patient Care;Patients;Pharmaceutical Preparations;pharmacologic;prevent;Proteomics;Public Health;Quality of life;Regulation;Relapse;Research;Role;Serum;Signal Pathway;small hairpin RNA;small molecule;supportive environment;System;Testing;Therapeutic;therapeutic evaluation;Toxic effect;Translating;Treatment Efficacy;Treatment Failure;Treatment Protocols;Up-Regulation;Work;Xenograft procedure

PROJECT_TITLE: Overcoming Leukemia Chemoresistance in the Central Nervous System

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


ORG_CITY: SEATTLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE The aim of this proposal is to better understand why venous clots in the legs sometimes dislodge and travel to the lungs. These clots block circulation to the lungs and are life-threatening. We are interested in identifying inherited factors that lead to clots traveling to the lung and learning how the inherited factors change the biologic function that causes a clot to dislodge.

PI_NAMEs: SMITH, NICHOLAS L (contact);WOLBERG, ALISA S.

PROGRAM_OFFICER_NAME: KINDZELSKI, ANDREI L

PROJECT_TERMS: activated Protein C;Anticoagulants;bioinformatics resource;Biological;Biological Assay;Biological Process;Biology;Blood flow;Candidate Disease Gene;Circulation;Classification;Clinical;Coagulation Process;Cohort Studies;Data;deep vein;Deep Vein Thrombosis;Diagnosis;Embolism;Event;experimental study;Factor V;Fibrinolysis;Functional disorder;Genes;Genetic;genetic information;genetic predictors;genetic risk factor;genetic variant;Genetic Variation;genome wide association study;genome-wide;genomic locus;Heart;Hemostatic function;insight;interest;International;Investigation;Knowledge;Laboratories;Learning;Leg;Life;Link;Linkage Disequilibrium;Lung;Meta-Analysis;mouse model;mutant;North Carolina;novel;Odds Ratio;Other Genetics;Pathology;Pelvis;Phenotype;Process;protein function;Proteins;Prothrombin;Pulmonary artery structure;Pulmonary Embolism;Pump;Research;Resistance;Resources;Risk;Risk Estimate;Structural Genes;Structure;Testing;Therapeutic Embolization;Thrombosis;Travel;Universities;Validation;Variant;Venous;venous thromboembolism;Venous Thrombosis;Work

PROJECT_TITLE: Genetic Discovery and Functional Validation to Identify Precursors of Clot Embolization in those with a Deep Vein Thrombosis

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


NIH_SPENDING_CATS: Genetics;Immunotherapy

ORG_DEPT: BIOCHEMISTRY

PHR: PROJECT NARRATIVE The healthy human immune system responds to pathogens in the body by rapidly increasing the number of lymphocytes, specialized cells that can identify and attack the invaders. This proposal focuses on the enzyme CTP synthase, which controls production of a key molecular building block that is needed to increase lymphocyte numbers. By learning how CTP synthase is controlled and how it can be inhibited we will lay the groundwork for therapies that suppress the immune system, for example in the treatment of hyperactive immune response in autoimmune diseases, or to prevent the rejection of transplanted organs.

PI_NAMEs: KOLLMAN, JUSTIN M (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Active Sites;Adopted;Affinity;Anabolism;Autoimmune Diseases;B Cell Proliferation;Binding;Binding Sites;Biochemical;Biological Assay;biophysical properties;Biophysics;Bypass;C-terminal;Cell Proliferation;Cells;Cellular Assay;Chemicals;Complex;Cryoelectron Microscopy;Defect;Dependence;design;Development;Disease;Dissection;DNA biosynthesis;drug development;Drug Targeting;Enzyme Inhibitor Drugs;Enzymes;Failure;Feedback;flexibility;Genes;Growth;Human;human tissue;Hyperactivity;Immune response;Immune system;immunodeficiency;Immunosuppression;Immunosuppressive Agents;Impairment;improved;in vitro activity;Inherited;inhibitor;insight;Learning;Leukocytes;loss of function mutation;Lymphocyte Count;lymphocyte proliferation;membrane synthesis;Metabolism;Molecular;Molecular Conformation;Mutagenesis;novel;novel therapeutics;Nucleotide Biosynthesis;Nucleotides;organ transplant rejection;pathogen;Pathway interactions;Peptides;Pharmaceutical Preparations;Phosphorylation;Physiological;Play;prevent;Production;Proliferating;Protein Isoforms;Pyrimidine Nucleotides;Regulation;Reporting;Resolution;Ribonucleotides;RNA chemical synthesis;Role;scaffold;side effect;small molecule inhibitor;Solid;Specificity;Structure;success;T-Lymphocyte;Tail;Testing;therapeutic development;Therapeutic immunosuppression;Tissues;tool;uptake;Work

PROJECT_TITLE: Structural basis for differential regulation and selective inhibition of human CTP synthase 1

STUDY_SECTION: MSFC

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


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

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

ORG_DEPT: VETERINARY SCIENCES

PHR: Narrative: We identified host protein filamin B as a novel regulator of both entry and exit of Ebola and Marburg viruses from mammalian cells. Here we seek to determine the molecular mechanism by which filamin B modulates these steps in the virus lifecycle. These studies will enhance our understanding of key virus-host interactions at the molecular level, which may lead to the development of new antiviral strategies to combat these infections.

PI_NAMEs: HARTY, RONALD N (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Actins;Affect;Anti-viral Therapy;Antibody Therapy;BAG3 gene;Biochemical;Biological Assay;Cell division;Cell Fractionation;Cell membrane;cell motility;Cell Physiology;Cell Separation;Cells;Cellular Morphology;Cessation of life;chronic infection;combat;Complex;confocal imaging;crosslink;Cytokinesis;Development;Disease Outbreaks;driving force;Ebola;Ebola virus;emerging pathogen;extracellular;Eye;Family;filamin;Filopodia;Filovirus;Future;Goals;HIV-1;Host Defense Mechanism;Human;Immunologics;Infection;insight;Integrins;Laboratories;Life Cycle Stages;Link;link protein;Liquid substance;long-term sequelae;Magnetism;Mammalian Cell;Marburgvirus;Mediating;member;Membrane;Microscopy;Molecular;nonhuman primate;novel;particle;Pathway interactions;Process;protein crosslink;Proteins;Proteome;Reagent;Recombinants;Regulation;Ribonucleases;Role;Seminal fluid;Site;Small Interfering RNA;Testing;Therapeutic Intervention;Total Internal Reflection Fluorescent;trafficking;ubiquitin-protein ligase;Vesicle;Vesicular stomatitis Indiana virus;Viral;Viral Hemorrhagic Fevers;Virion;Virus;Virus Assembly;Virus Diseases;virus host interaction;Virus Replication;Zoonoses

PROJECT_TITLE: Role of Host Filamin Proteins in Regulating Filovirus Entry and Egress

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]