NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: Columbus

ORG_DEPT: NEUROSCIENCES

ORG_NAME: OHIO STATE UNIVERSITY

PHR: The Exploration in Neuroscience Research for High School Students provides substantive research experiences and professional development activities to support future participation of high school students, including those typically underrepresented in neuroscience, in undergraduate neurological disease research, neuroscience majors, and careers in neuroscience research. This program is designed to provide a strong foundation for early neuroscientists to excel in competitive research programs.

PI_NAMEs: ASKWITH, CANDICE C (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Address;Adolescence;Alzheimer's Disease;Area;Attitude;Bachelor's Degree;Biomedical Research;career;Career Choice;Child;Cognitive;cohort;college;Critiques;Databases;Dedications;design;Development;Disease;Educational workshop;Effectiveness;Ensure;Environment;expectation;experience;Exposure to;Faculty;field study;Foundations;Future;Goals;graduate student;hands on research;High School Student;Individual;interest;Learning;Link;Long-Term Effects;Measures;Mentors;metropolitan;Middle School Student;Mind;Nerve Degeneration;Nervous System Disorder;Nervous System Trauma;Neurology;Neuronal Injury;Neurosciences;Neurosciences Research;outreach;Participant;Postdoctoral Fellow;Process;programs;Published Comment;Research;Research Activity;Research Design;Research Personnel;Research Project Grants;Secure;skills;Societies;Solid;Students;Surveys;tool;Training;Training and Education;Training Programs;Traumatic injury;undergraduate education;undergraduate research;undergraduate research experience;undergraduate student;Underrepresented Populations;Work;young adult

PROJECT_TITLE: Explorations in Neuroscience Research For High School Students


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Assistive Technology;Behavioral and Social Science;Bioengineering;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Kidney Disease;Neurosciences;Pain Research;Palliative Care;Patient Safety;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: PROJECT NARRATIVE Pain is a highly common and morbid condition among persons with end-stage kidney disease (ESKD) requiring hemodialysis (HD). Because the current method of managing pain in this population typically involves the use of analgesic medications that confer substantial health risks, novel non-drug therapies are needed to reduce pain and lessen reliance on opioid and other drug therapies. We will undertake a randomized controlled trial to determine the efficacy of an at-home neuromodulatory device to mitigate pain and improve other outcomes (e.g., mood, quality of life) in a stratified sample to include approximately equal numbers of Hispanics, non- Hispanic Blacks, and non-Hispanic white ESKD patients requiring HD.

PI_NAMEs: DHINGRA, LARA K;REID, MANNEY CARRINGTON (contact)

PROGRAM_OFFICER_NAME: ABBOTT, KEVIN C

PROJECT_TERMS: Address;Adherence;Adult;Adverse effects;adverse outcome;Affect;Age;Analgesics;biological sex;Black American;Black Populations;Black race;Body mass index;Cephalic;Characteristics;Chronic;Chronic Disease;chronic pain;chronic pain management;Client satisfaction;Clinical;Cognitive;Consumption;Depressed mood;Devices;Disease;efficacy evaluation;End stage renal failure;Enrollment;Ensure;ethnic diversity;ethnic minority;Ethnic Origin;Ethnic Population;evidence base;experience;Face;falls;follow-up;follower of religion Jewish;Fracture;Health;Healthcare Systems;Hemodialysis;Hispanic;Hispanic Populations;Home;Hospitalization;improved;innovation;Interdisciplinary Study;Knowledge;Long-Term Effects;Medicine;metropolitan;minimal risk;Minority;Minority Groups;Minority Status;Mission;Moods;mortality;Motor Cortex;neuroregulation;Nonpharmacologic Therapy;Not Hispanic or Latino;novel;Opioid;opioid therapy;Outcome;Pain;Pain intensity;Pain interference;Pain management;Pain Management Method;pain reduction;Palliative Care;Participant;patient population;Patients;people of color;Persons;Pharmaceutical Preparations;Pharmacotherapy;Population;post intervention;Practice Management;Prevalence;primary outcome;Procedures;Protocols documentation;Quality of life;Race;racial minority;racial population;Randomized;Randomized, Controlled Trials;Reporting;Risk;Safety;Sample Size;Sampling;satisfaction;secondary outcome;side effect;sociodemographics;Supervision;Tablets;telehealth;Telephone;Therapeutic Intervention;Time;transcranial direct current stimulation;treatment arm;treatment effect;Treatment outcome;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Delivery of an At-Home Nonpharmacologic Intervention (Transcranial Neurostimulation) to Mitigate Pain in Patients with End Stage Kidney Disease Receiving Hemodialysis

STUDY_SECTION: CMGC

STUDY_SECTION_NAME: Clinical Management in General Care Settings Study Section[CMGC]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: VANCOUVER

ORG_COUNTRY: CANADA

ORG_FIPS: CA

ORG_NAME: UNIVERSITY OF BRITISH COLUMBIA

ORG_STATE: BC

ORG_ZIPCODE: V6T 1Z3

PHR: Project Narrative. The relevance of this project comes from the pressing need to control fungal infections in humans with impaired immune systems. In particular, the >37 million people infected with HIV have a high chance of succumbing to fungal diseases. The research will specifically examine the potential to control these infections by targeting the ability of fungal pathogens to acquire iron as a vital nutrient during infection. !

PI_NAMEs: KRONSTAD, JAMES W (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;anti-fungal agents;Binding;capsule;Cell surface;Cells;Ceruloplasmin;Cessation of life;combat;Communication;comparative genomics;Complex;Cryptococcosis;Cryptococcus;Cryptococcus gattii;Cryptococcus neoformans;Cysteine;detection of nutrient;Disease;Drug Targeting;Environment;functional genomics;fungus;Gene Expression;Genetic Screening;glutaredoxin;Goals;Growth;Heme;heme a;HIV;Homeostasis;Human;Immune system;Immunocompetent;Impairment;In Vitro;in vivo;Infection;Infection Control;Inhalation;Iron;Iron Chelation;Knowledge;Knowledge acquisition;Lead;Link;Location;Mammals;Membrane;Meningoencephalitis;Mitochondria;mitochondrial membrane;Modeling;Molecular Analysis;mouse model;Mus;mutant;Mutation;Mycoses;new therapeutic target;novel therapeutic intervention;novel therapeutics;Nutrient;Nutritional;Nutritional Immunity;pathogen;pathogenic fungus;Patients;permease;Persons;Pharmaceutical Preparations;Phenotype;Play;Polysaccharides;Process;Productivity;programs;Proliferating;protein complex;protein function;Proteins;Proteomics;Regulation;Research;Role;sensor;Siderophores;Signal Transduction;Site;Structure;System;Testing;Tissues;trafficking;transcription factor;United States National Institutes of Health;uptake;Vaccines;Vacuole;Virulence;Virulence Factors

PROJECT_TITLE: Comparative and functional genomics of C. neoformans

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Clinical Research;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Prevention;Rare Diseases;Social Determinants of Health;Vector-Borne Diseases;Zika Virus

ORG_CITY: SANTA CRUZ

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

ORG_STATE: CA

PHR: The goal of this proposal is to develop a rapid, sensitive, low-cost, and easy-to-use diagnostic technology for diagnostics of arboviral infections in point-of-care settings. In our preliminary experiments with serum samples, we demonstrated that our novel approach is 10,000 fold more sensitive than the most sensitive ELISA tests. Our goal is to develop our novel approach into a standalone diagnostic unit, validate it with PCR measurements, and field-test in Grenada. The proposed studies will take advantage of the considerable resources and expertise at University of California, Santa Cruz (UCSC) and Stanford University, the established febrile human disease surveillance and archived serum banks from Kenya, the established human disease surveillance in Grenada, as well as industry expertise in development and production of antibodies specific to non-structural 1 protein (NS1), recombinant NS1 proteins and anti-IgM antibodies.

PI_NAMEs: YANIK, AHMET ALI (contact)

PROGRAM_OFFICER_NAME: DYALL, JULIE

PROJECT_TERMS: Acute;Animals;anti-IgM;Antibodies;Antibody Formation;arboviral disease;Arbovirus Infections;Arboviruses;Archives;Area;arthropod-borne;biodefense;Biological Assay;Blood;Blood specimen;California;Chikungunya virus;Chronic;Clinical;clinical diagnostics;Collaborations;cost;cost effective;Country;Dengue Virus;design;Detection;detection assay;Development;Diagnosis;Diagnostic;diagnostic platform;diagnostic strategy;diagnostic technologies;Diagnostic tests;diagnostic tool;disease diagnostic;Disease Outbreaks;Disease Outcome;Disease Surveillance;disease transmission;Early Diagnosis;Education;emerging pathogen;Endemic Diseases;Engineering;Enzyme-Linked Immunosorbent Assay;Epidemic;experimental study;Fever;field study;Foundations;Geography;Goals;Grant;Grenada;Health;high risk;Human;human disease;improved;Industry;Infection;Infectious Disease Epidemiology;Infrastructure;Island;Kenya;Laboratories;Location;Measurable;Measurement;Medical;Microfluidics;Molecular;Molecular Virology;multidisciplinary;multiplex detection;nanoengineering;nanophotonic;National Institute of Allergy and Infectious Disease;new technology;novel;novel diagnostics;novel strategies;Nucleic Acid Amplification Tests;pathogen;Patients;Phase;Plasma;point of care;Population;Populations at Risk;portability;programs;Proteins;prototype;Public Health;Recombinants;Research;Resource-limited setting;Resources;Risk;Sampling;Scheme;Serum;Special Equipment;Surveillance Program;Symptoms;System;Technology;Testing;Time;tool;Training;transmission process;United States National Institutes of Health;Universities;Validation;Viral;Viral Antigens;viral detection;Virus;Work;Zika Virus

PROJECT_TITLE: Sample-to-Answer, Rapid, Multiplexed and PCR-Free Diagnostics of Arboviral Diseases in Resource Limited Settings

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-U(02)M]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE  In adults, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic cancer with a poor overall survival, high relapse rate, and significant treatment-related side effects due to intense chemotherapy regimens. Using mouse genetic models and primary T-ALL patient samples, this project will study the importance of JAK/STAT signaling in the pathology of T-ALL driven by loss-of-function DNMT3A mutations. The main goal of these research efforts is the development of precision medicine approaches for DNMT3A- mutant adult T-ALL patients, a group with poor clinical outcomes and no established standard-of-care for relapsed patients.

PI_NAMEs: CHALLEN, GRANT ANTHONY (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Acute T Cell Leukemia;acute T-cell lymphoblastic leukemia cell;Adult;Adult Precursor B Lymphoblastic Leukemia;Adult Precursor T Lymphoblastic Leukemia;Apoptosis;Automobile Driving;BCL2L1 gene;Binding;Biological Assay;Biological Process;Cell Death;Cell Proliferation;Cell Survival;Cells;Central Nervous System;Chemoresistance;chemotherapeutic agent;chemotherapy;Chemotherapy-Oncologic Procedure;Child;Childhood Precursor T Lymphoblastic Leukemia;Clinical;clinical prognosis;Combined Modality Therapy;Coupled;CRISPR/Cas technology;cytokine;Development;Disease-Free Survival;DNA Methylation;DNA Modification Methylases;DNMT3a;DNMT3a mutation;Dose;Down-Regulation;Enhancers;Enzymes;gain of function mutation;Gene Expression;Generations;Genetic;Genetic Enhancer Element;Genetic Models;Genome;Genome engineering;genome sequencing;Genomics;Goals;Hematologic Neoplasms;Hematopoietic Neoplasms;high risk;high risk population;Human;Hypersensitivity;IL7 gene;Impairment;in vivo;Inferior;inhibitor;Interleukin-6;leukemia;Link;loss of function;lymphadenopathy;Maintenance;Malignant - descriptor;Malignant Neoplasms;Modeling;Molecular;Molecular Abnormality;mouse genetics;mouse model;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;Neoplasms;NOTCH1 gene;novel;novel therapeutic intervention;Oncogenic;Outcome;Pathogenesis;Pathology;patient derived xenograft model;patient population;Patient-Focused Outcomes;Patients;Phenotype;Positioning Attribute;precision medicine;Prognosis;programs;PTPN6 gene;rational design;Reagent;Recurrence;Relapse;relapse patients;Research;Resistance;Role;Sampling;Signal Transduction;standard of care;Stat5 protein;stem cells;Stress;Survival Rate;System;T-Cell Lymphoma;T-Cell Transformation;T-Lymphocyte;Testing;Time;tool;Treatment outcome;Treatment Side Effects;treatment strategy;Tumor Suppressor Proteins;Up-Regulation;virulence gene;White Blood Cell Count procedure

PROJECT_TITLE: JAK/STAT signaling in the pathogenesis of DNMT3A mutant T-ALL

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Congenital Structural Anomalies;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: Boulder

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: How do we generate all the right numbers of neural stem cells and differentiated neural cell types that make up the brain and spinal cord? Disruption of this highly coordinated process can result in neurodevelopmental disorders such as microcephaly or macrocephaly. Our studies explore a new set of non-coding RNAs that control the balance between proliferation and differentiation, and their relationship to proteins that are known to be associated with the birth defect, microcephaly.

PI_NAMEs: NISWANDER, LEE A. (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Address;Animal Model;ATRX gene;Attention;Biogenesis;Brain;Brain Diseases;Bruck-de Lange syndrome;cell behavior;Cell Differentiation process;Cell Line;Cell Maintenance;Cell Survival;cell type;Chromosome Cohesion;Chromosome Deletion;Chromosome Segregation;cohesin;cohesion;Complex;Congenital Abnormality;CRISPR/Cas technology;CSPG6 gene;Data;Defect;Deletion Mutation;Development;Developmental Process;Embryo;Ensure;Equilibrium;Exons;Functional disorder;Gene Mutation;Genes;Genetic;Goals;Growth;Human;In Vitro;in vivo;knock-down;Knock-out;Knowledge;Link;Macrocephaly;Mediating;Methyl-CpG-Binding Protein 2;Microcephaly;MicroRNAs;Mitosis;Mitotic;Modeling;Molecular;mouse model;Multiprotein Complexes;Mus;Mutate;nerve stem cell;Nervous System Disorder;Neurodegenerative Disorders;neurodevelopment;Neurodevelopmental Disorder;Neuroepithelial;Neuronal Differentiation;Neuronal Injury;Neurons;neuroregulation;novel;Patients;Pattern;Phenotype;Play;Polyadenylation;prevent;Process;progenitor;Proliferating;Protein Isoforms;Proteins;Regulation;Rett Syndrome;RNA;Role;scaffold;Sister Chromatid;Spinal Cord;stem cell biology;stem cell proliferation;stem cell self renewal;stem cell survival;stem cells;Syndrome;Testing;Transcript;Untranslated RNA

PROJECT_TITLE: Non-coding RNA regulation of early neural development

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Iron overload disorders and iron-restricted anemias are the most common hematological diseases worldwide. Many of these disorders are caused by altered expression of the liver secreted hormone hepcidin, thus considerable interest exists in understanding hepcidin transcriptional regulation. Knowledge gained from this proposed project will help understand the role of Syndecan-1 as an hepcidin regulator and a putative novel therapeutic target that can be used to treat iron-overload disorders and iron-restricted anemias.

PI_NAMEs: GORDTS, PHILIP  (contact)

PROGRAM_OFFICER_NAME: ROY, CINDY

PROJECT_TERMS: absorption;Anemia;Anemia due to Chronic Disorder;Antisense Oligonucleotides;Automobile Driving;BMP6 gene;Bone Morphogenetic Proteins;Brucella abortus;Characteristics;Chronic Kidney Failure;Circulation;clinically relevant;Complex;CRISPR/Cas technology;dietary;Disease;disease model;efficacy evaluation;Enterocytes;Erythrocytes;Erythropoiesis;Exhibits;Functional disorder;Genetic;Goals;Hematological Disease;Heparan Sulfate Biosynthesis;Heparan Sulfate Proteoglycan;Heparitin Sulfate;Hepatic;Hepatocyte;hepatoma cell;hepcidin;Homeostasis;Hormone secretion;Hormones;Human;IL6 gene;improved;Induced Hepatocytes;induced pluripotent stem cell;Inflammation;interest;Interleukin-6;Iron;iron absorption;iron metabolism;Iron Overload;Knowledge;Ligands;Liver;Macrophage;Measures;Mediating;metal transporting protein 1;Modeling;mouse model;Mus;mutant;Natural History;new therapeutic target;novel;pharmacologic;pre-clinical;prevent;Proteomics;receptor;reconstitution;Recycling;Regulation;Risk Reduction;Role;Signal Transduction;Signaling Protein;Structure;syndecan;System;Testing;Tissues;Trace Elements;Transcriptional Regulation

PROJECT_TITLE: Investigating Syndecan-1 in Hepcidin Regulation and Iron Metabolism

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-C(02)]


NIH_SPENDING_CATS: Kidney Disease

ORG_CITY: BOSTON

ORG_NAME: TUFTS MEDICAL CENTER

ORG_STATE: MA

PHR: Narrative Kidney function is usually estimated from markers that are measured in the blood, but current estimates are less accurate for people with chronic illness, such as those with heart or liver failure, or diverse racial, ethnic and geographic groups. The current project will fill this important gap in knowledge by developing a simple method to estimate kidney function from markers that can be easily measured from a single blood draw and that is more accurate than current estimates for all people across the continuum of health and disease. More accurate kidney function estimates will enable better clinical decision making for patients, more rigorous research designs, and better estimates of the public health burden of chronic kidney disease in the United States.

PI_NAMEs: INKER, LESLEY ANN (contact)

PROGRAM_OFFICER_NAME: CHAN, KEVIN E

PROJECT_TERMS: access restrictions;Adverse event;analytical method;Benchmarking;Biological;Biological Assay;biomarker evaluation;biomarker panel;Black race;Blood;Blood specimen;candidate selection;Caring;Characteristics;Chronic Disease;Chronic Kidney Failure;Clinical;clinical decision-making;clinical practice;Clinical Practice Guideline;cohort;Collaborations;cost efficient;Creatinine;Cystatins;Data;demographics;design;Development;Diet;Disease;Dose;Epidemiology;Equation;Ethnic Origin;Evaluation;experience;Filtration;Foundations;Geography;Glomerular Filtration Rate;Goals;Health;Health Services Accessibility;Heart failure;Hospitalization;improved;Individual;Inflammation;innovation;Investigation;Joints;Kidney Diseases;Knowledge;Laboratories;Liquid Chromatography;Liver Failure;marginalization;mass spectrometer;Mass Spectrum Analysis;Measures;metabolomics;Methods;Modeling;multiplex assay;Muscular Atrophy;novel;novel strategies;Obesity;Outcome;outcome prediction;Participant;patient population;Patients;Persons;Pharmaceutical Preparations;Physiological;Population;Population Heterogeneity;post gamma-globulins;predictive modeling;Prognosis;Property;Public Health;Race;racial diversity;reduced muscle mass;Renal function;Research;Research Design;Science;Serum;Statistical Methods;Techniques;Testing;United States;Validation;Weight;Work

PROJECT_TITLE: Improving Kidney Function Assessment in Health and Disease

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Kidney Disease;Regenerative Medicine

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Project Narrative Chronic kidney disease is common and causes serious complications – including loss of kidney function. With a goal to protect against loss of function, the proposed studies will investigate a new potential therapeutic target – Par1 signaling. The mechanisms to be examined may also be important in kidney repair after acute kidney injury.

PI_NAMEs: REIDY, KIMBERLY JEAN (contact)

PROGRAM_OFFICER_NAME: BRUNSKILL, ERIC WAYNE

PROJECT_TERMS: Ablation;Activities of Daily Living;Acute;Acute Renal Failure with Renal Papillary Necrosis;Adult;Cell Cycle;Cell Differentiation process;Cells;Chronic;Chronic Kidney Failure;Clinical;Compensation;Data;Development;Dialysis procedure;Disease Progression;Epithelial Cells;epithelial stem cell;Epithelium;Family;Fibrosis;Folic Acid;Gene Expression;Goals;Human;human disease;Impairment;in vivo;Infiltration;Inflammatory;inhibitor;Injections;Injury;Injury to Kidney;innovation;insight;interstitial;Kidney;Kidney Diseases;kidney fibrosis;kidney repair;knock-down;Knowledge;Laboratories;Link;loss of function;LoxP-flanked allele;member;Membrane;Modeling;mouse model;Mus;Myofibroblast;new therapeutic target;notch protein;Notch Signaling Pathway;novel;Pathway interactions;Persons;pharmacologic;Phosphotransferases;prevent;Proliferating;Protein Family;Protein-Serine-Threonine Kinases;Recovery;Regulation;Renal function;Renal tubule structure;repaired;Reperfusion Injury;response;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;stem cell population;stem cell proliferation;stem cells;synergism;targeted treatment;Testing;Tetanus Helper Peptide;therapeutic target;Time;tool;Tubular formation;Up-Regulation;Ureteral obstruction;WNT Signaling Pathway

PROJECT_TITLE: Cell specific Partitioning Defective Par1a/b deletion effects on renal repair

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


ADMINISTERING_IC: HG

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Data Science;Genetics;Human Genome

ORG_CITY: CHAMPAIGN

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it increases the accessibility and, importantly, the diversity of genomic data available to researchers - thereby increasing both equity and the pace of advancement in genomic science - and facilitates Open Science practices in genomic research through a novel technical solution called sign and mask, which simultaneously ensures the integrity of the data and protects the security and privacy of potential research participants. This project will make it technically possible to bring genomic analyses to existing genomic data in the possession of direct-to-consumer service users for the purpose of study recruitment, conduct a robust legal and regulatory analysis for distributed analysis on next-generation genomic sequencing data, and identify the factors that lead laypeople and genomic researchers to accept and use sign and mask and home genetic testing technologies. Thus, the proposed research is relevant to part of the NHGRI’s mission in seeking to create a more inclusive precision medicine.

PI_NAMEs: GUNTER, CARL A (contact)

PROGRAM_OFFICER_NAME: LOCKHART, NICOLE C

PROJECT_TERMS: Acceleration;Adopted;Adoption;Algorithms;Attitude;Belief;Cellular Phone;Computers;Data;data access;data ecosystem;data integrity;Data Set;data sharing;Databases;Democracy;design;digital;Distant;Dreams;Ecosystem;Elements;Enhancement Technology;Ensure;Equity;ethnic diversity;Face;Failure;Genetic;genetic testing;Genome;genome integrity;genome sciences;genomic data;Genomics;Goals;Hand;Home;improved;in silico;Individual;Infrastructure;innovation;Intention;Knowledge;Lead;Legal;Masks;Methodology;Methods;Mission;Modeling;Motivation;National Human Genome Research Institute;new technology;next generation;novel;open data;Participant;Persons;Policies;precision medicine;prevent;Principles of law and justice;Privacy;Privatization;Process;Protocols documentation;prototype;Public Health;racial diversity;recruit;Research;Research Methodology;Research Personnel;Rights;Risk;Security;Services;social;Source;System;Technology;Technology Assessment;Testing;Time;trend;United States National Institutes of Health;usability;volunteer;Work

PROJECT_TITLE: A Sociotechnical Approach to Improving Security and Privacy in the Genomic Data Ecosystem


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF EDUCATION

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Racial and Ethnic Minority Health Research

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE  We will develop a test of morphosyntax for identifying developmental language disorder (DLD) in bilingual children based on their English language performance. We will translate information about DLD in Spanish- English bilinguals and extend this to Vietnamese-English bilinguals. The outcome will be a test, given in English, that will help the 94% of speech language pathologists who speak only English identify DLD in bilingual children.

PI_NAMEs: PEÑA, ELIZABETH D (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: 11 year old;Affect;Age;Benchmarking;bilingualism;biomarker identification;Characteristics;Child;Child Language;Childhood;Classification;Clinical;Clinical Markers;clinical practice;Data;Data Set;Development;Diagnostic;disability;Early treatment;English Language;English Learner;Ensure;Evaluation;experience;field study;Focus Groups;health disparity;Home;Human Development;Impairment;Incidence;indexing;instrument;Intervention Studies;Knowledge;knowledge base;Language;Language Development;Language Development Disorders;language impairment;language outcome;Language Tests;Learning;Linguistics;Literature;Measures;Outcome;Output;Pathologist;Performance;pilot test;Population;Procedures;Publishing;recruit;Reduce health disparities;remediation;Reporting;Research;Research Personnel;response;Risk;Role;Schools;secondary analysis;skills;Spanish;Spanish/English;Speech;Statistical Models;Structure;Testing;theories;Time;tool;Translating;Typology;Vietnamese;Work

PROJECT_TITLE: Test of English Language Learning (TELL)


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Cocaine;Genetics;HIV/AIDS;Infectious Diseases;Lung;Prevention;Pulmonary Hypertension;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE University of Kansas Medical Center Research Institute, Inc. The proposed research will have an important positive impact on human health because understanding the basis of pathogenesis and identification of long non-coding RNAs related mechanism(s) involved in the development of HIV and/or drugs of abuse associated vascular remodeling are expected to provide new targets for therapeutic interventions that will aid the growing number of HIV-infected and/or intravenous drug users. In addition, the results will fundamentally advance the field of cardio-pulmonary vascular research in general.

PI_NAMEs: DHILLON, NAVNEET KAUR (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: Animal Model;antiretroviral therapy;Apoptosis;Apoptotic;BCL1 Oncogene;BCL2L1 gene;Binding;Bioinformatics;Biological Assay;Biological Process;Blood;Blood Vessels;Cardiopulmonary;Cell Culture Techniques;Cell Cycle Progression;cell growth;Cell Proliferation;cell type;Chronic Obstructive Pulmonary Disease;Cocaine;cocaine exposure;Combined Modality Therapy;comorbidity;Detection;Development;differential expression;Drug abuse;drug abuser;drug of abuse;Early Diagnosis;Exposure to;Functional disorder;gene repression;Genes;Health;Heart;HIV;HIV-1;HIV/AIDS;Human;Hyperplasia;Illicit Drugs;in vivo;Individual;Inhibition of Cell Proliferation;inhibitor;innovation;intravenous drug user;Kansas;knock-down;Light;Link;Lung;lung vascular injury;Macaca;Mediating;Medical center;Micro Array Data;Microarray Analysis;Modeling;mRNA Expression;new therapeutic target;non-drug;novel;overexpression;Pathogenesis;Pathogenicity;Patients;Phenotype;pre-clinical;Prevalence;prevent;Preventive;Proliferating;Protein Isoforms;Proteins;Publishing;pulmonary arterial hypertension;pulmonary arterial pressure;Pulmonary Emphysema;Pulmonary Hypertension;pulmonary vascular disorder;pulmonary vascular remodeling;Rat Transgene;Rattus;Regulation;Reporting;Research;Research Institute;Resistance;response;Right Ventricular Dysfunction;right ventricular failure;Risk;RNA;RNA Splicing;RNA-Binding Proteins;Role;SIV;Sleep;Smooth Muscle;Smooth Muscle Myocytes;Structure of parenchyma of lung;Study models;Systolic Pressure;Therapeutic Intervention;tumor;Universities;Untranslated RNA;Up-Regulation;Vascular Diseases;vascular injury;Vascular remodeling;Ventricular

PROJECT_TITLE: Drug abuse and HIV-associated pulmonary vascular injury

STUDY_SECTION: HVCD

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


ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE HIV post-treatment controllers (PTCs) are individuals who can maintain virologic suppression after interruption of antiretroviral therapy and represent a natural model of sustained HIV remission. However, our understanding of the virologic determinants of HIV remission remains incomplete, which is in part due to the scarcity of PTCs identified through any one research center or clinical trial, and in part because of the limited scope of viral reservoir studies that have been performed to date. The main goal of this proposal is to perform an in-depth virologic analysis of PTCs and our overarching hypotheses are that HIV reservoir characteristics can provide mechanistic insights behind their ability to achieve HIV remission.

PI_NAMEs: LI, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: Aftercare;Anti-Retroviral Agents;antiretroviral therapy;ATAC-seq;Biological Assay;Biological Markers;Characteristics;Chromatin;Clinical Trials;cohort;Complex;design;Disease remission;Distal;DNA;Ecology;Environment;experience;Gene Silencing;Genetic Transcription;Genome;Goals;HIV;holistic approach;Individual;insight;integration site;International;Interruption;Laboratories;Length;Location;Lymph Node Tissue;Measures;Modeling;Molecular;novel;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;Persons;Pharmaceutical Preparations;Poly A;Polyadenylation;Proviruses;Reporting;Research;Research Personnel;RNA;RNA Splicing;T memory cell;T-Lymphocyte Subsets;Therapeutic Intervention;Tissues;Transcription Initiation;Transcriptional Regulation;transcriptome sequencing;transcriptomic profiling;Viral;viral rebound;Viral reservoir;Withholding Treatment

PROJECT_TITLE: HIV Reservoir Ecology of Viral Remission

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


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

ORG_CITY: PITTSBURGH

ORG_DEPT: BIOLOGY

ORG_NAME: CARNEGIE-MELLON UNIVERSITY

ORG_STATE: PA

PHR: NARRATIVE Although inhibition prevents runaway excitation that can destabilize brain circuits and lead to epilepsy, it must be at least briefly suppressed in order for cortical plasticity and learning to occur. Here we will investigate how a specific type of inhibitory neuron controls cortical activity during reinforcement learning. We hope to discover fundamental mechanisms about stimulus- reward coupling in neocortical circuits that will inform strategies for learning across diverse paradigms and species.

PI_NAMEs: BARTH, ALISON L (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Acetylcholine;Acute;Anatomy;Association Learning;Aversive Stimulus;barrel cortex;Brain;Cells;cholinergic;cost;Coupled;Coupling;Data;Desire for food;Detection;Disinhibition;Environment;Epilepsy;excitatory neuron;experience;experimental study;Feedback;Fire - disasters;hippocampal pyramidal neuron;In Vitro;in vivo;inhibitory neuron;Interneurons;Learning;learning strategy;Maps;Mediating;Memory;Mental Depression;Minor;Modeling;Molecular;Mus;Neocortex;neocortical;neural;Neurons;optogenetics;Output;Parvalbumins;patch clamp;Pattern;Perception;Phase;Play;prevent;Probability;Psychological reinforcement;Research;Rewards;Role;Runaway;Sensory;sensory cortex;sensory input;Signal Transduction;Skin;Slice;Somatosensory Cortex;Somatostatin;Source;Stimulus;Synapses;Synaptic plasticity;Tactile;Testing;Thalamic structure;Time;Touch sensation;Training;Vasoactive Intestinal Peptide;Vibrissae;Water

PROJECT_TITLE: Determinants of sparse activity in neocortex

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-SMN-B(90)S]


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE Multiple sclerosis is an inflammatory demyelinating and neurodegenerative disease of the central nervous system. While current anti-inflammatory therapies are effective during the initial phase of the disease, they have limited success as the disease progresses, and in some cases even increase disease severity. Our proposed studies aim to understand how cells of the nervous and immune systems communicate to promote neuroprotection and reveal novel therapeutic targets that prevent neurodegeneration and disease progression during chronic phases of MS.

PI_NAMEs: WILLIAMS, JESSICA L (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Acute;Adult;Animal Model;Anti-Inflammatory Agents;Area;Astrocytes;Autoimmunity;Autopsy;Axon;Biological Response Modifiers;Brain;Cell Survival;Cells;Central Nervous System;Central Nervous System Diseases;Chronic;Chronic Disease;Chronic Phase;Chronic Progressive Multiple Sclerosis;CNS autoimmunity;Communication;cytokine;Data;Demyelinating Diseases;Development;disability;Disease;Disease Progression;Excision;Experimental Autoimmune Encephalomyelitis;Functional disorder;Goals;Homeostasis;IFNGR1 gene;Immune;Immune system;immunoregulation;improved;In Vitro;in vivo;Inflammation;Inflammatory;Injury;Interferon Type II;Kinetics;Lesion;Maintenance;Mediating;mouse model;multicatalytic endopeptidase complex;Multiple Sclerosis;Multiple Sclerosis Lesions;multiple sclerosis patient;Mus;Myelin;Nerve Degeneration;Nervous System;Nervous System Physiology;Neurodegenerative Disorders;neuroinflammation;Neurons;neuropathology;neuroprotection;new therapeutic target;novel;novel therapeutic intervention;Oligodendroglia;oxidative damage;Oxidative Stress;Pathogenesis;Pathologic;Pathway interactions;pharmacologic;Phase;Phenotype;prevent;Process;protein aggregation;Proteins;Proteome;proteostasis;Reactive Oxygen Species;repaired;Research;Resolution;restoration;Role;Severity of illness;Signal Transduction;Source;Spinal Cord;Spinal Cord Lesions;success;Symptoms;Testing;therapeutic target;Tissues;Up-Regulation;white matter;young adult

PROJECT_TITLE: The role of the astrocyte immunoproteasome during chronic CNS autoimmunity

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: TAMPA

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Sepsis is a life-threatening disease arising from dysregulated host response to infection. There are limited diagnostic tools or effective drugs to treat this problem. This study examines the molecular property and function of novel molecules produced during septic injury that contribute to multiple organ dysfunction, with the potential to develop new diagnostic and therapeutic targets for effective treatment of infectious diseases.

PI_NAMEs: WU, MACK H;YUAN, SARAH Y (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: 3-Dimensional;Address;Affect;Age;Animal Model;Animal Organ;Animals;Bacteremia;Bacterial Infections;Bacterial Pneumonia;Bacterial Toxins;Biological Assay;Biological Markers;Blood Circulation;blood perfusion;Blood Vessels;Cells;Circulation;Communicable Diseases;comparative;Complex;Coupled;Critical Illness;Cytoskeleton;design;Development;Diagnostic;diagnostic tool;Disease;Disintegrins;effective therapy;Endothelial Cells;Endothelium;Enzymes;experimental study;Exposure to;extracellular;Extravasation;Functional disorder;Future;Glycocalyx;Glycoproteins;Glycosaminoglycans;Goals;Human;Immune response;Infection;infectious disease treatment;Inflammatory;Inflammatory Response;Injury;innovation;innovative technologies;insight;Intercellular Junctions;intravital microscopy;Invaded;knockout gene;Knowledge;Life;Link;Lipopolysaccharides;Liquid substance;Lung;Lung infections;Measures;Mediating;Mediator;Mesentery;Metalloproteases;Microcirculation;MicroRNAs;microscopic imaging;Modeling;Molecular;Molecular Target;Morphology;mortality;multidisciplinary;Multiple Organ Failure;nanoimaging;Nanotechnology;new therapeutic target;novel;novel diagnostics;optoacoustic tomography;Organ;overexpression;pathogen;Pathogenesis;Pathologic;Pathway interactions;Peptides;Perfusion;Permeability;Pharmaceutical Preparations;pharmacologic;Plasma;Play;Prevention;Process;Production;Property;Proteins;Proteoglycan;Proteomics;Pseudomonas aeruginosa;Regional Perfusion;Research Personnel;response;response to injury;Role;Sepsis;septic;sex;Signal Transduction;Structure;Surface;syndecan;systemic inflammatory response;Techniques;technology platform;Testing;Therapeutic;therapeutically effective;Time;tissue oxygenation;Tissues;Toxin;Translating;ultra high resolution;Up-Regulation;Vascular Endothelial Cell;vascular inflammation;Work

PROJECT_TITLE: Endothelial glycocalyx shedding in septic injury

STUDY_SECTION: SAT

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


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: MILWAUKEE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Project Narrative Dopamine receptors play important roles in human dopamine signaling pathway; therefore, targeting these membrane proteins provide promising therapies for many diseases, including schizophrenia, Huntington's disease, cognitive disorders and Parkinson’s disease. Here we propose to resolve the structure of human dopamine D1 like receptor (D1R), along with the relevant G protein complexes. We expect the structural information we obtain from this study will facilitate allosteric modulation and activation mechanism studies, and therefore benefit rational design of safer and more efficacious therapeutics.

PI_NAMEs: LIU, WEI  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: addiction;Address;Adherence;Affinity;Agonist;antagonist;Antibodies;Area;Arizona;Attentional deficit;Behavior;Binding;Clinical Research;Cognition Disorders;Collaborations;Complex;Computational Biology;computer studies;Cryoelectron Microscopy;Crystallization;design;Development;Disease;Docking;Dopamine;Dopamine D1 Receptor;dopamine D3 receptor;Dopamine Receptor;Drug Design;drug discovery;electron diffraction;Family;Family member;Feedback;Foundations;Future;G-Protein-Coupled Receptors;Goals;GTP-Binding Proteins;Human;Huntington Disease;Hyperactivity;Image;insight;Knowledge;Laboratories;Ligand Binding;Ligands;medical schools;member;Membrane Proteins;Mental Depression;Molecular;molecular modeling;nanobodies;Nerve;Nervous System;Nervous System Disorder;Neurons;neurotransmission;Neurotransmitters;novel therapeutics;Parkinson Disease;Pathway interactions;Play;positive allosteric modulator;preclinical study;Process;protein complex;Protein Family;protein structure;Proteins;rational design;receptor;receptor binding;Receptor Signaling;Research;research and development;Resolution;Rewards;Roentgen Rays;Role;Schizophrenia;screening;side effect;Signal Pathway;Signal Transduction;Signaling Protein;Site-Directed Mutagenesis;Solid;structural biology;Structure;Structure-Activity Relationship;success;System;Techniques;Technology;Testing;Therapeutic;Therapeutic Intervention;Therapeutic Studies;therapeutic target;three dimensional structure;Universities;Work;X-Ray Crystallography;x-ray free-electron laser

PROJECT_TITLE: Structural Biology of Dopamine Signaling

STUDY_SECTION: MSFC

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


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Primary Immunodeficiencies;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Stem Cell Research - Umbilical Cord Blood/ Placenta;Stem Cell Research - Umbilical Cord Blood/ Placenta - Non-Human

ORG_CITY: MADISON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: PROJECT NARRATIVE  Elucidating mechanisms that regulate blood cell development is critical for devising novel therapeutics, e.g. for anemia insensitive to erythropoiesis-stimulating agents or GATA2-deficiency syndrome involving immunodeficiency and myelodysplastic syndrome, and innovating strategies to generate blood cells for transplantation therapies. We discovered enhancers essential for blood stem cell generation/function and progenitor cell differentiation, and mechanistic dissection of the enhancers and downstream processes has generated new scientific paradigms and clinical practice to screen for genetic variation in the enhancers. Our multidisciplinary studies utilizing human disease mutations, innovative mouse models, primary cell rescue assay and multiomics will enable testing of how enhancer-regulated networks govern stem/progenitor cells and suppress development of blood diseases in which therapies are critically needed.

PI_NAMEs: BRESNICK, EMERY H (contact)

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: Acute Myelocytic Leukemia;Address;Alleles;AML/MDS;Anemia;Base Pairing;Biological Assay;Blood;Blood Cells;Bone marrow failure;Cells;Chromatin;Chronic Myeloid Leukemia;CISH gene;Clinical;clinical center;clinical practice;Code;cohort;Cytokine Signaling;Data;Development;Disease;Dissection;Dissociation;DNA Binding;Dysmyelopoietic Syndromes;Elements;Enhancers;Erythrocytes;Erythroid;erythroid differentiation;Erythropoiesis;EVI1 gene;Exhibits;forging;Foundations;Functional disorder;Funding;G-Protein-Coupled Receptors;gain of function;gain of function mutation;GATA2 deficiency;Gene Expression;Generations;Genes;Genetic;Genetic Determinism;Genetic Screening;Genetic Transcription;Genetic Variation;Genomics;granulocyte;Granulopoiesis;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hematopoietic System;Heterozygote;Human;human disease;IFN consensus sequence binding protein;immunodeficiency;Immunologic Deficiency Syndromes;Impairment;innovation;insight;Interferons;Life;Link;loss of function;Macrophage;Modeling;monocyte;mouse model;Mouse Strains;multidisciplinary;multiple omics;Mus;mutant;Mutant Strains Mice;Mutation;Myelopoiesis;Myeloproliferative disease;Natural regeneration;novel therapeutics;Nucleotides;Pathology;Pathway interactions;Predisposition;Process;progenitor;Proteins;Proteome;Proteomics;Proto-Oncogene Protein c-kit;receptor;regenerative;Regulation;Reporting;response;Signal Transduction;Site;stem cell biology;stem cell differentiation;stem cell fate;stem cell function;stem cells;Syndrome;System;Testing;transcriptome;transcriptomics;transplantation therapy;Up-Regulation

PROJECT_TITLE: Hematopoietic Regulation via GATA Switches

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-C(02)M]


NIH_SPENDING_CATS: Clinical Research;Physical Injury - Accidents and Adverse Effects

ORG_CITY: BURLINGTON

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: The endothelial surface lines all blood vessels, serving as the nexus between blood and the body, and forming a membrane that directs coagulation and innate immune responses to injury. This project will elucidate mechanisms by which the endothelium detects histones and will test therapeutic strategies to protect the endothelial cells from maladaptive coagulation responses after severe trauma.

PI_NAMEs: FREEMAN, KALEV  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acute;Biology;Blood;Blood flow;Blood Vessels;burden of illness;Clinical;Coagulation Process;Diagnosis;Disease;Endothelial Cells;endothelial dysfunction;Endothelium;Health;Health Care Costs;Histones;Impairment;improved;improved outcome;Inflammation;Injury;Innate Immune Response;Intervention;Membrane;Molecular;molecular modeling;novel strategies;programs;Research;response;response to injury;Role;Signal Transduction;Surface;Syndrome;Testing;therapeutic evaluation;Translating;Trauma;Trauma patient;Vascular Endothelium

PROJECT_TITLE: Molecular Mechanisms of Histone-Induced Endotheliopathy in Trauma

STUDY_SECTION: MRAC

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


ADMINISTERING_IC: DA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Networking and Information Technology R&D (NITRD);Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Telehealth;Tobacco;Tobacco Smoke and Health

ORG_CITY: HERSHEY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: Project Narrative This project focuses on improving the impact of mobile health (mHealth) technology among African Americans using state quitline services. This research has implications for how smoking cessation interventions are designed with the potential to reduce disparities in tobacco-caused diseases. This project has the potential to be expanded to other state quitlines and leverage the use of advanced statistical methodologies such as just- in-time adaptive interventions (JITAIs).

PI_NAMEs: ALLEN, SOPHIA I. (contact)

PROGRAM_OFFICER_NAME: FITZ-RANDOLPH, MARCY ESTHER

PROJECT_TERMS: Abstinence;Academic Medical Centers;adaptive intervention;addiction;Address;Adult;African American;African American population;automated text message;Award;Behavior;Behavior assessment;Black Populations;Black race;Cancer Etiology;career development;Career Mobility;Cessation of life;Characteristics;Cigarette;cigarette smoking;Clinical Research;Communities;Consumption;Counseling;craving;Data;Data Analyses;Data Set;design;Disease;Disparity;disparity reduction;Ecological momentary assessment;Enrollment;Environment;Environmental Risk Factor;Equipment;evidence base;experience;follow-up;Funding Agency;Goals;health disparity;Health Technology;improved;Individual;Intervention;Interview;K-Series Research Career Programs;Knowledge;Life Expectancy;Mentors;Methodology;Methods;mHealth;mhealth interventions;Minority Groups;Mobile Health Application;Monitor;Moods;Motivation;National Institute of Drug Abuse;Nicotine;nicotine replacement;Participant;participant enrollment;participant interview;Pennsylvania;Perception;Persons;Pharmacotherapy;pilot test;post-doctoral training;premature;preventive intervention;programs;Public Health;quitline;racial minority;relapse prevention;Reporting;Research;Research Methodology;Research Personnel;Research Support;Resources;Risk Reduction;secondary analysis;service engagement;Services;skills;Smoke;Smoker;Smoking;smoking abstinence;smoking cessation;Smoking Cessation Intervention;Smoking Status;social culture;social determinants;social health determinants;social influence;sociocultural determinant;Socioeconomic Status;substance use;Technology;technology intervention;Text Messaging;therapy design;Time;Tobacco;tobacco regulatory science;Training;Translating;varenicline

PROJECT_TITLE: Mixed methods research to increase engagement and smoking abstinence among African Americans enrolled in Quitline text messaging services

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


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

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Project Narrative  This research will contribute to a greater understanding of the origin of aortic valve malformations including bicuspid aortic valve that can lead to disease and rupture of the major blood vessel, the aorta. There are currently no drugs that can treat valve diseases. Our approach is aimed at developing new drug targets that recognize common factors found in diseased valve tissues that contribute to tissue damage and their inability to direct blood flow to the body.

PI_NAMEs: KERN, CHRISTINE BRUINS (contact)

PROGRAM_OFFICER_NAME: EVANS, FRANK

PROJECT_TERMS: Active Sites;ADAMTS;Adult;Affect;aggrecan;Amino Acids;Aneurysm;Aorta;Aortic Rupture;aortic valve;aortic valve disorder;Arteries;ascending aorta;Behavior;bicuspid aortic valve;Blood flow;Blood Vessels;Cardiac;Cardiovascular system;cell behavior;Cell Lineage;Cells;comorbidity;congenital heart abnormality;Coronary artery;Data;Defect;Degenerative polyarthritis;design;Development;Disease;Elasticity;Endothelium;Event;Exhibits;experimental study;Extracellular Matrix;Fetus;Heart Valves;Human;in vivo;Individual;inhibitor;insight;Investigation;Label;Lasers;malformation;Mesenchymal;Metabolism;Modeling;Molecular;Morphology;mouse model;Mus;Mutation;Myocardial;Neural Crest;new therapeutic target;Organ;Patients;Pattern;Penetrance;Pharmaceutical Preparations;Pregnant Women;Prevalence;prevent;Proteoglycan;Publishing;Reporting;Reproducibility;Research;Risk Factors;Role;Rupture;side effect;Signal Transduction;Stromelysin 1;Sudden Death;targeted sequencing;Testing;Therapeutic;therapeutic target;therapeutically effective;Tissues;transcriptome sequencing;versican

PROJECT_TITLE: Proteoglycan Metabolism During Cardiac Valve Development and Disease

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


NIH_SPENDING_CATS: Clinical Research;Diabetes;Digestive Diseases;Liver Disease;Microbiome;Nutrition;Obesity

ORG_CITY: ATLANTA

ORG_DEPT: MISCELLANEOUS

ORG_NAME: GEORGIA STATE UNIVERSITY

ORG_STATE: GA

PHR: Public Health Relevance Statement: Humanity is facing an epidemic of interrelated obesity-associated metabolic disorders including insulin resistance, hyperglycemia, hyperlipidemia, and hepatic steatosis, collectively referred to as metabolic syndrome (Met Syn). Estimates for incidence of Met Syn range from 50-80 million Americans, many of whom will develop morbid diseases including type 2 diabetes, cardiovascular disease, and liver failure. This project seeks to better understand mechanisms that drive Met Syn thus paving the way to develop novel means to combat this public health emergency.

PI_NAMEs: GEWIRTZ, ANDREW T (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: 16S ribosomal RNA sequencing;Ablation;Adipocytes;Adipose tissue;American;Antibiotics;Antibodies;Antigens;Applications Grants;Automobile Driving;Bacteria;Biopsy;Cardiovascular Diseases;Chronic;Colon;combat;Cost of Illness;Coupled;Diabetes Mellitus;Diet;diet-induced obesity;Disease;endoplasmic reticulum stress;Epidemic;Event;Exhibits;Fatty Liver;Flagellin;Food Supply;gastrointestinal epithelium;Gene Expression;Genetic Engineering;Germ-Free;Gnotobiotic;gut microbiota;host microbiota;Human;Humanities;Hyperglycemia;Hyperlipidemia;Hypertension;Immune system;Immunization;immunodeficiency;Immunoglobulin A;Incidence;Industrialization;Infiltration;Inflammation;Inflammatory;Insulin;Insulin Resistance;Intestines;laser capture microdissection;Leptin;Lipids;Liver;Liver Failure;Metabolic;Metabolic Diseases;Metabolic syndrome;Metabolism;microbiome;microbiota;Mucosal Immunity;Mucous body substance;Mucous Membrane;Mus;nanoparticle;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Oral;Organ;pathobiont;Phagocytes;prevent;public health emergency;public health relevance;response;Role;Signal Pathway;Signal Transduction;Sterility;TLR5 gene;Toll-like receptors;Training;Vaccinated;western diet;Work

PROJECT_TITLE: DECONSTRUCTING INFLAMMATION AND ALTERED MICROBIOTA IN METABOLIC SYNDROME

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-P(02)]


ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: Project Narrative Higher brain functions such as learning, memory and cognition require synaptic plasticity, i.e. the controlled changes in the strength of the connections between neurons. Conditions such as global cerebral ischemia (GCI) and Alzheimer's disease (AD) cause not only neuronal cell death, but also impaired synaptic plasticity in the surviving neurons. Based on strong preliminary data, this proposal will elucidate the mechanisms how GCI causes both, neuronal cell death and impaired plasticity. Importantly, this proposal will develop an intervention to prevent cell death and to possibly even restore the impairments in synaptic plasticity. Together, the results will further our understanding of the mechanisms underlying both neuronal cell death and functional impairment of the surviving neurons. Additionally, the results will directly aid the development of a new therapeutic intervention.

PI_NAMEs: BAYER, K. ULRICH  (contact);HERSON, PACO S

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Ablation;Affect;Alzheimer's Disease;Amyloid beta-Protein;Binding;Brain;calmodulin-dependent protein kinase II;Cardiopulmonary Resuscitation;Cell Death;Cell Survival;Cerebral Ischemia;Clinical Trials;clinically relevant;Cognition;Data;deprivation;Development;Excitatory Synapse;excitotoxicity;experimental study;Family suidae;Functional impairment;Future;Genetic;Glucose;Heart Arrest;Human;Impairment;in vivo;Individual;Induced Neurons;Informed Consent;inhibitor;Injections;Intervention;Ischemia;Knockout Mice;Learning;Literature;Long-Term Potentiation;Mediating;Mediator;Memory;Mental Depression;Modeling;Molecular;motor impairment;Movement;Mus;Mutant Strains Mice;N-Methyl-D-Aspartate Receptors;natural hypothermia;neuron loss;neuronal survival;Neurons;neuroprotection;Nitric Oxide Synthase Type I;novel therapeutic intervention;optimal treatments;Outcome;Oxygen;Pathologic;Pathway interactions;Pharmacological Treatment;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Preparation;prevent;Publishing;Regulation;restoration;Risk Factors;Role;Signal Transduction;standard of care;Synaptic plasticity;Testing;Therapeutic;Therapeutic Intervention;Time;Validation;Ventricular Fibrillation;Work

PROJECT_TITLE: CaMKII in global cerebral ischemia: mechanisms and therapeutic intervention

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR-M]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Schizophrenia;Serious Mental Illness;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BIRMINGHAM

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative Schizophrenia is a serious mental illness associated with significant societal and personal costs as well as early mortality. A consistent finding in schizophrenia brain is disruptions in energy usage leading to increased acidity. Here, I propose to study a group of proteins called sodium hydrogen exchangers that help regulate the pH of cells in schizophrenia brain in order to identify new treatment targets for this illness.

PI_NAMEs: PRUETT, BRANDON SCOTT (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Acidity;Acute;Affect;AMPA Receptors;Astrocytes;Autopsy;Biology;Brain;brain tissue;Calibration;cancer cell;career;Cell Culture Techniques;Cell membrane;cell type;Cells;Closure by clamp;Co-Immunoprecipitations;Confocal Microscopy;cost;Development;Diagnosis;Disease;Doctor of Philosophy;economic cost;Endosomes;Energy Metabolism;Enrollment;Enzymes;Excision;experience;experimental study;first episode schizophrenia;Fluorescence;Funding;Future;Glycolysis;Goals;Health;high throughput screening;Hypoxia;Individual;induced pluripotent stem cell;Knowledge;Learning;Measures;Mediating;Mentorship;Metabolic;Methods;Modeling;Molecular;mortality;multimodality;neuroimaging;Neurons;Neurotransmitter Receptor;new therapeutic target;novel;novel therapeutics;Organelles;patient derived induced pluripotent stem cells;Patients;Peripheral;Pharmaceutical Preparations;PHluorin;pluripotent stem cell differentiation;Positioning Attribute;Post-Translational Protein Processing;Pre-Clinical Model;Prefrontal Cortex;professor;programs;protein distribution;protein transport;Proteins;Psychiatry;Psychopathology;ratiometric;receptor;Regulation;Reporting;Research Personnel;Research Project Grants;Residencies;Resolution;response;Role;Scaffolding Protein;Schizophrenia;severe mental illness;skill acquisition;Sodium-Hydrogen Antiporter;Stress;stressor;Subcellular Fractions;Synapses;Techniques;Testing;Time;Tissues;trafficking;Training;Transfection;Universities;Visualization;Work

PROJECT_TITLE: Organellar Na+/H+ Exchangers and Intracellular pH Regulation in Schizophrenia Brain


ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Cancer genomes are shaped by mutation and chromosome rearrangement. Understanding mutational processes driving these alterations advances our understanding of how cancer develops and has potential to lead to new cancer therapies. Building on preliminary work, we propose to elucidate the essential mechanistic steps of catastrophic mutational processes termed chromothripsis and chromoplexy.

PI_NAMEs: PELLMAN, DAVID S (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Address;Adenine;Aneuploidy;Automobile Driving;Base Excision Repairs;cancer genome;cancer therapy;Cell division;Cell Nucleus;Cell Separation;Cells;Chromatin;Chromosomes;chromothripsis;Coupled;Cytoplasm;Data;Deaminase;Defect;deoxyinosine;Deoxyribonucleases;Development;DNA;DNA biosynthesis;DNA Damage;DNA glycosylase;DNA replication fork;DNA sequencing;DNA-Directed DNA Polymerase;ds-DNA;egg;endonuclease;Evolution;experimental study;Exposure to;fitness;Fluorescence;Funding;Genetic Transcription;Genome;genome sequencing;Genome Stability;Goals;Grant;Hybrids;In Vitro;Interphase;Interphase Chromosome;Knock-out;live cell imaging;Malignant Neoplasms;Mass Spectrum Analysis;micronucleus;Mitosis;Mitotic;Mitotic Chromosome;Mitotic spindle;Modeling;Mutation;novel;Nuclear Envelope;Nuclear Structure;Oncogenic;Outcome;Pathway interactions;Pattern;Polyploidy;Process;Proteins;Purines;Reporter;RNA;Rupture;Series;Shapes;Single-Stranded DNA;Structure;System;Testing;Transcriptional Regulation;whole genome;Work;Xenopus

PROJECT_TITLE: Polyploidy, Aneuploidy and Genome Stability

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Cardiovascular;Duchenne/ Becker Muscular Dystrophy;Heart Disease;Heart Disease - Coronary Heart Disease;Hematology;Muscular Dystrophy;Pediatric;Pediatric Cardiomyopathy;Prevention;Rare Diseases;Sickle Cell Disease

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Narrative Although calcium (Ca) and iron (Fe) are known to play vital cellular roles in the heart, when there is dysregulation of these two ions there are different pathways that can result in myocardial damage and systolic failure. Under specific biological pathologies, multiple signaling pathways can dictate the susceptibility of cardiomyocytes to contractile failure. We propose that it is an active cross talk and cellular signaling between dysregulation of both Fe and Ca that leads to myocardial contractile failure, ischemia reperfusion injury and ultimately cardiomyopathy (CM). We will identify triggers and signaling pathways that are involved in the observed systolic and diastolic dysfunction and ferroptosis associated with iron induced CM and Duchenne muscular dystrophy associated CM. We will also create an E-C Mitochondria (ECM) coupling 3D network model based on our experimental findings to be used in an interpretative as well as predictive fashion. Our project will therefore address broad scientific as well as clinical questions with regard to the mechanism of clinical myocardial stunning, I/R injury, and CM.

PI_NAMEs: GWATHMEY, JUDITH K;XIE, LAI-HUA  (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: 3-Dimensional;Acute;Address;American;Animal Model;beta Thalassemia;Biological;Biological Markers;Blood Transfusion;Calcium;calcium uniporter;Cardiac;Cardiac Myocytes;Cardiomyopathies;Cardiotoxicity;Cause of Death;Cell Death;Cell Death Induction;Cell Physiology;Cells;Chelation Therapy;Clinical;Computer Models;Coupling;Cytosol;Data;Dependence;Development;Diastolic heart failure;Dilated Cardiomyopathy;Duchenne cardiomyopathy;Duchenne muscular dystrophy;Environment;Exhibits;Failure;Functional disorder;Genes;Genetic Diseases;Heart;Heart Diseases;Hereditary hemochromatosis;Homeostasis;Human;In Vitro;in vivo;inhibitor;Injury;insight;Intervention;Ion Channel;Ions;Iron;Iron Chelation;Iron Overload;Ischemia;Lead;life span;Link;Lipid Peroxidation;lipidomics;Lipids;Mediating;Mitochondria;Molecular;mouse model;Mus;Muscle Cells;Muscular dystrophy cardiomyopathy;Myocardial;myocardial damage;Myocardial dysfunction;Myocardial Infarction;myocardial injury;Myocardial Stunning;network models;novel;oxidation;Oxidative Stress;Participant;Pathology;Pathway interactions;Patients;Persons;Play;Predisposition;Prevention;Preventive therapy;Proteins;Reaction;receptor;Regulation;Reperfusion Injury;Reperfusion Therapy;Reporting;Role;Running;Sickle Cell Anemia;Signal Pathway;Signal Transduction;simulation;SLC11A2 gene;targeted treatment;Testing;tool;United States;uptake;Volatilization;Western Blotting;Woodchuck

PROJECT_TITLE: Ferroptosis in the Heart: Iron Calcium Crosstalk and Compartmentalization

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Nutrition;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: SAN DIEGO

ORG_DEPT: NUTRITION

ORG_NAME: SAN DIEGO STATE UNIVERSITY

PHR: NARRATIVE Hispanics/Latinos are the largest minority group in the U.S. and have a high prevalence of cardiovascular disease (CVD) risk factors, which is further compounded by the large proportion of Hispanics/Latinos living in poverty and experiencing food insecurity. Mobilizing existing capital (i.e. assets) to promote food security and a healthy diet may contribute to reducing CVD risk among low-income Hispanics/Latinos, but in-depth evidence on the sources of capital influential to food security, diet, and CVD risk is limited. This proposed research will address these gaps by using data from an existing Hispanic/Latino cohort to identify sources of capital that promote food security, a healthy diet, and cardiovascular health, and then apply these results, along with results from qualitative data, to develop a pilot intervention for low-income, Hispanic/Latino adults that targets influential sources of capital to promote cardiovascular health.

PI_NAMEs: MCCLAIN, AMANDA CHRISTINE (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: Address;Adopted;Adult;Ancillary Study;Area;bean;Behavior;Capital;cardiometabolism;cardiovascular disorder risk;cardiovascular health;Cardiovascular system;career development;Caregivers;Clinical Trials;cohort;Communities;Community Healthcare;Complement;Coronary heart disease;Data;Data Analyses;Diastolic blood pressure;Diet;dietary;Dietary intake;Economic Conditions;Elements;Epidemiology;Evaluation;Exhibits;experience;Fiber;Focus Groups;Food;Food Access;food insecurity;food security;Funding;Goals;good diet;Health;health equity;Health Insurance;Health protection;Healthcare;High Density Lipoprotein Cholesterol;High Prevalence;high risk;Hispanic;Hispanic Community Health Study/Study of Latinos;Hispanic Populations;Household;Human;implementation research;improved;Influentials;innovation;Intake;interest;Intervention;intervention mapping;Intervention Studies;Interview;Knowledge;Latino;Latino Population;Leadership;Low income;member;Mentored Research Scientist Development Award;Mentors;Mentorship;Metabolic syndrome;Methodology;Methods;Minority Groups;mortality;National Heart, Lung, and Blood Institute;Not Hispanic or Latino;nutrition;Outcome;Participant;Personal Attribute;Pilot Projects;Poverty;prevent;Process;programs;protective factors;Protocols documentation;Public Health;Qualitative Research;recruit;Research;Research Methodology;Research Personnel;Research Proposals;Resources;Risk Factors;Risk Marker;Role;Shapes;skills;social;social culture;sociocultural determinant;socioeconomics;Source;Statistical Data Interpretation;Training;Triglycerides;Typology;Uninsured;uptake;waist circumference;Work;Youth

PROJECT_TITLE: Capacity-oriented approaches to food security, diet quality, and cardiovascular disease risk among Hispanics/Latinos

STUDY_SECTION: MCBS

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


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Aging;Amyotrophic Lateral Sclerosis (ALS);Bioengineering;Biotechnology;Brain Disorders;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_DEPT: CHEMISTRY

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Project Narrative Protein misfolding and aggregation underpin several neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. While there are no effective treatments for these disorders, the application of protein disaggregases like Hsp104 is an innovative strategy to tackle these disorders. I aim to understand more about Hsp104’s intrinsic function and develop the technology to engineer Hsp104 variants that dissolve aggregates associated with disease which could simultaneously counter both a loss or gain of function mechanism.

PI_NAMEs: RYAN, JEREMY  (contact)

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Aging;alpha synuclein;Alzheimer's Disease;Amyloid;amyloid fibril formation;Amyloid Fibrils;Amyotrophic Lateral Sclerosis;Animal Model;Bacteria;Biosensor;Cell Line;Cells;Chemosensitization;Collection;conformer;Data;deep sequencing;design;Development;Disease;disease phenotype;DNA Sequence Alteration;dopaminergic neuron;effective therapy;efficacy evaluation;efficacy validation;Engineering;Ensure;experimental study;Failure;Fluorescence Resonance Energy Transfer;fungus;Future;gain of function;Generations;Goals;high throughput analysis;Homologous Gene;Human;human disease;improved;innovation;insight;Learning;Lewy Bodies;Libraries;Life;Link;Mammalian Cell;Modeling;motor neuron degeneration;Mutation;Neurodegenerative Disorders;Neuroglia;Neurons;novel therapeutics;Parkinson Disease;Pathology;Patients;Pilot Projects;Plants;Prions;Property;protein aggregation;Protein Dynamics;Protein Engineering;protein folding;protein misfolding;protein TDP-43;Proteins;Proteome;proteostasis;Regulatory Pathway;Role;screening;Structure;Substrate Specificity;Surveys;System;Techniques;Technology;Testing;Therapeutic;Toxic effect;trend;Variant;yeast prion;yeast protein;Yeasts

PROJECT_TITLE: Engineering and evolving substrate-specific Hsp104 variants


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cerebrovascular;Neurosciences

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: Project Narrative In this project, we will analyze adhesion and signaling cascades regulated by integrins and determine how they promote blood vessel development in the brain and retina. We will also study how genetically targeting components of these pathways lead to vascular pathologies. !

PI_NAMEs: MCCARTY, JOSEPH H (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Address;Adhesions;Affinity;age related;age related neurodegeneration;Arteries;Avidity;Binding;Biochemical;Biological Assay;Biology;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood capillaries;blood vessel development;Blood Vessels;Brain;brain endothelial cell;Brain Pathology;Cardiovascular system;Cell Adhesion;cell behavior;Cell Communication;Cell Culture System;Cell Physiology;cell type;Cells;Central Nervous System;Communication;Complex;Cytoplasm;Cytoplasmic Tail;Cytoskeleton;Data;Development;developmental disease;Disease;Dissection;Docosahexaenoic Acids;Down-Regulation;Endothelial Cells;Endothelium;Event;experimental study;extracellular;Extracellular Domain;Extracellular Matrix;Extracellular Matrix Proteins;fetal;Fluorescence Microscopy;Focal Adhesions;Functional disorder;Gene Expression;Genetically Engineered Mouse;Growth Factor;Homeostasis;human disease;Image;insight;integrin alphavbeta8;Integrins;Internet;Ions;Knock-in;Knock-in Mouse;Laboratories;Lead;Ligands;Link;link protein;Mediating;Membrane;Metabolism;Microglia;Modeling;Morphogenesis;mouse model;Mus;mutant mouse model;Mutant Strains Mice;Mutation;Nerve Degeneration;Nervous System Disorder;neural;Neurocognitive Deficit;Neuroglia;Neurologic Deficit;neurological pathology;Neurons;neuropathology;neurovascular;neurovascular unit;Organ;Paracrine Communication;Pathogenesis;Pathology;Pathway interactions;Pericytes;Perinatal subependymal hemorrhage;Permeability;Physiology;Play;Polyunsaturated Fatty Acids;pre-clinical;Primary Cell Cultures;Property;Proteins;receptor;Regulation;Resolution;Retina;Role;Signal Pathway;Signal Transduction;Stroke;Structure;Tight Junctions;tool;transcriptome sequencing;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;Vascular Dementia;Vascular Endothelial Cell;Vascular System;Vascularization;Veins

PROJECT_TITLE: Signal Transduction by alphavbeta8 Integrin

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG-M]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Lung;Machine Learning and Artificial Intelligence;Pediatric;Precision Medicine;Sleep Research

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: Obstructive sleep apnea is a serious upper-airway condition in children, as chronic lack of sleep causes many problems such as developmental delay and heart abnormalities; however, surgeries aimed at relieving symptoms are often not successful. In this proposal a combination of fast magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) will be used to assess how inhaled air interacts with the anatomy of the airway to predict how this will change after surgery. We believe these techniques will allow surgeons a far better means to predict the best surgical path for each individual patient and will improve their quality of life.

PI_NAMEs: BATES, ALISTER  (contact)

PROGRAM_OFFICER_NAME: DIXIT, SHILPY

PROJECT_TERMS: 3-Dimensional;Acceleration;Adenoidal structure;Affect;Air;Air Movements;Air Pressure;airway obstruction;Airway Resistance;Anatomy;Apnea;Artificial Intelligence;Award;Behavioral;Biomechanics;Biometry;Breathing;candidate validation;Cardiovascular system;career;career development;Child;Childhood;Chronic;Clinical;Cognitive;Computer Models;computerized tools;Continuous Positive Airway Pressure;Data;design;Developmental Delay Disorders;Disease;Environment;Event;experience;Face;Failure;Gases;Geometry;Goals;Growth;Heart Abnormalities;Hour;Image;imaging Segmentation;Impairment;improved;improved outcome;In Vitro;in vivo;indexing;Individual;individual patient;Inhalation;Ionizing radiation;Knowledge;Liquid substance;Lung;Machine Learning;Magnetic Resonance Imaging;Maps;Measurement;Measures;Medicine;Mentors;Metabolic;Methods;Modality;Modeling;Morbidity - disease rate;Motion;neuromuscular;Noble Gases;non-compliance;novel;Obstructive Sleep Apnea;Operative Surgical Procedures;Outcome;Patients;Pattern;Pediatric Hospitals;pediatric patients;Phase;Physiology;Polysomnography;positive airway pressure;Postoperative Period;precision medicine;predictive modeling;predictive tools;pressure;Pulmonology;Quality of life;Radiology Specialty;reduce symptoms;Research;Research Personnel;Resistance;Resolution;respiratory;Respiratory Airflow;respiratory surgery;Shapes;simulation;skills;Sleep;Sleep Apnea Syndromes;Sleep disturbances;Soft Palate;soft tissue;Structure;success;Surgeon;surgery outcome;Techniques;Testing;Time;Tongue;Tonsil;tool;Validation;virtual;virtual model;virtual surgery;Wing;Xenon

PROJECT_TITLE: Improving Outcomes in Pediatric Obstructive Sleep Apnea with Computational Fluid Dynamics

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: HD

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

ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: PROJECT NARRATIVE The PIWI/piRNA pathway is a highly conserved mechanism responsible for the maintenance of genomic integrity in the germline which is primarily responsible for the silencing of transposons during sperm and egg development. Aberrant transposon activity in the germline can cause DNA damage leading to heritable mutations associated with both infertility and birth defects, and has been implicated in the production of heat- induced DNA damage in developing sperm but not eggs. Understanding how sexually dimorphic piRNA pathway responses to heat stress regulate gene expression, including transposons, in developing sperm and eggs will contribute to our understanding of infertility, birth defects and miscarriage.

PI_NAMEs: KURHANEWICZ, NICOLE A (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: Acute;Affect;Caenorhabditis elegans;ChIP-seq;Chromatin;Congenital Abnormality;Data;Deposition;derepression;Development;DNA;DNA Damage;DNA Transposable Elements;DNA Transposons;egg;Elements;Exposure to;Female;Fertility;follow-up;Functional disorder;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene repression;Gene Silencing;Gene Targeting;Generations;Genes;genetic element;Genome;genome integrity;Genomics;Germ Cells;Germ Lines;Heat Stress;Heat-Shock Response;Heritability;Histone H3;histone modification;Immunofluorescence Microscopy;Impairment;Infertility;insight;knock-down;Light;Link;Lysine;Maintenance;male;Male Infertility;Mediating;Monitor;Mutation;Oocytes;Pathway interactions;piRNA;Prevention;programs;Pseudogenes;Publishing;Regulation;Repression;Research;response;Role;sex;Sex Differences;sexual dimorphism;Site;Small RNA;sperm cell;Spermatocytes;Spontaneous abortion;Testing;Thermogenesis;transcriptome sequencing;Transposase;Work

PROJECT_TITLE: Regulation of sexually dimorphic piRNA pathways in heat-induced infertility

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Reproduction, Andrology, and Gynecology Study Section[CHHD-R]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Contraception/Reproduction;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Women's Health Research

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

ORG_STATE: CA

PHR: Project Narrative We will generate a new model of trophoblast organoid using human induced pluripotent stem cells, replicating the early stage of gestation from normal and preeclamptic pregnancies and will evaluate novel drugs that target pathways unique to humans with preeclampsia.

PI_NAMEs: KARUMANCHI, S. ANANTH (contact)

PROGRAM_OFFICER_NAME: VARAGIC, JASMINA

PROJECT_TERMS: 3-Dimensional;Abnormal placentation;Activities of Daily Living;Address;Angiogenesis Inhibitors;Angiogenic Proteins;Binding;Biological Markers;Blood Circulation;Blood Vessels;Cardiovascular system;Cell Culture System;Cell Line;cell type;Cells;Cellular biology;Cerebral Palsy;Cessation of life;Chromosome 13;Circulation;Clinical;comparison control;Complex;Complication;cytotrophoblast;Data;Defect;Development;Developmental Process;Discipline of obstetrics;Disease;Drug Screening;early onset;Eclampsia;Endothelial Cells;endothelial dysfunction;Endothelial Growth Factors Receptor;epidemiology study;Epithelium;Etiology;Event;Exhibits;experimental study;fetal;Fetus;Fibroblasts;First Pregnancy Trimester;FLT1 gene;Functional impairment;Genes;Genetic;Goals;Greater sac of peritoneum;HELLP Syndrome;Human;human embryonic development;human induced pluripotent stem cells;human model;Hypertension;Hypoxia;Immunocompromised Host;Impairment;Implant;improved;in vivo evaluation;induced pluripotent stem cell;infancy;Invaded;Ischemia;Kidney Failure;Laboratories;Lead;Length;LTK gene;Maternal complication;Mediating;Membrane;Methods;Modeling;Monoclonal Antibodies;Mothers;Mus;neonatal morbidity;Neonatal Mortality;Nervous System Trauma;new therapeutic target;nonhuman primate;novel;novel therapeutics;Nude Mice;Organ;Organoids;Patau's syndrome;Pathogenesis;Pathologic;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Physiology;Placenta;placental trophoblasts;Placentation;Pre-Eclampsia;precision medicine;Pregnancy;pregnancy disorder;Premature Birth;Primates;Protein Isoforms;Proteinuria;Protocols documentation;Rapid screening;receptor;Regenerative Medicine;Reproducibility;Research Personnel;Risk;Rodent;Seizures;self-renewal;Signal Transduction;Signs and Symptoms;Small for Gestational Age Infant;Specimen;stem cell population;stem cells;Stroke;Structure;Syncytiotrophoblast;Syndrome;Testing;therapeutic candidate;therapeutic evaluation;three dimensional cell culture;Time;Tissues;trophoblast;Uterus;Vascular Endothelial Growth Factor Receptor-1;Vascular Endothelial Growth Factors;Villous;Woman

PROJECT_TITLE: Placental Organoids to Model Preeclampsia

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_STATE: MO

PHR: PROJECT NARRATIVE The need for effective subunit vaccines has prompted the development of combination adjuvants that stimulate multiple pathways of innate immunity for eliciting durable and protective immunity. In this project we will evaluate the molecular mechanisms by which peptide nanofiber adjuvants that induce damage-associated molecular patterns (DAMPs) synergize with pathogen-associated molecular patterns (PAMPs) to enhance adaptive immune response against antigens. Successful completion of the project will lead to an improved understanding of combinatorial adjuvant design for developing effective and safe subunit vaccines.

PI_NAMEs: RUDRA, JAI  (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Acetylmuramyl-Alanyl-Isoglutamine;adaptive immune response;adaptive immunity;Adjuvant;Agonist;aluminum sulfate;Antigen Presentation;Antigens;Autophagocytosis;CD8-Positive T-Lymphocytes;cell injury;Cell Maturation;Cell Physiology;Cells;Cellular Immunity;Charge;Chemicals;Chemistry;combinatorial;cytokine;Dendritic cell activation;Dendritic Cells;design;Development;Disease;Dissection;dosage;efficacy validation;Emulsions;engineered T cells;Ensure;Experimental Designs;Flow Cytometry;Formulation;Goals;Human;Hydrophobicity;Immune;Immune response;Immune signaling;Immunity;Immunize;immunogenicity;Immunologic Adjuvants;Immunology procedure;improved;in vivo;Individual;Infection;Inflammation;Innate Immune Response;insight;Investigation;Knockout Mice;Licensing;Lung;Mediating;Metabolism;MHC Class I Genes;microbial;Molecular;Morphology;mouse model;Mus;nanofiber;nanomaterials;Natural Immunity;Osmosis;Outcome;Oxidative Stress;pathogen;Pathway interactions;Pattern;Pattern recognition receptor;Peptides;Phenotype;Production;Property;receptor;response;Safety;self assembly;Signal Pathway;Signal Transduction;Small Interfering RNA;stoichiometry;Subunit Vaccines;synergism;T cell response;T-Lymphocyte;Testing;tissue resident memory T cell;Tissues;TLR2 gene;Toll-like receptors;transcriptome sequencing;translational potential;Tuberculosis;Vaccination;Vaccine Adjuvant;vaccine immunogenicity;vaccine response;Vaccines

PROJECT_TITLE: Mechanisms of Nanomaterials-based Combination Adjuvants

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


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

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: NARRATIVE Carbapenem-resistant Klebsiella pneumoniae ‘superbugs’ cause life-threatening infections and have been classified as an urgent public health threat. Current antibiotic treatment options for carbapenem-resistant Klebsiella pneumoniae are not sustainable due to the development of resistance and clinical treatment failures. This highlights the critical importance of the current project, which will rationally develop precise combination treatment approaches for these deadly pathogens.

PI_NAMEs: BULMAN, ZACKERY P. (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Algorithms;Aminoglycoside resistance;Aminoglycosides;Antibiotic Therapy;Antibiotics;bacterial resistance;beta-Lactamase;beta-Lactams;Biological Assay;Blood Circulation;carbapenem resistance;Categories;Ceftazidime;Classification;Clinical;Clinical Research;Clinical Treatment;Clinical Trials;clinically relevant;combat;Combined Modality Therapy;Data;data modeling;Data Set;Death Rate;design;Development;dosage;Dose;Enzymes;Failure;Fiber;Foundations;Future;genetic signature;global health;Goals;Human;Imipenem;improved;In Vitro;in vivo;Infection;inhibitor;innovation;insight;Life;Medicine;Meropenem;Modeling;Molecular;mouse model;Mus;nephrotoxicity;novel;Outcome;pathogen;Penetration;Pharmacodynamics;Pharmacology;pneumonia model;predictive modeling;Predisposition;prospective;Protein Biosynthesis;Public Health;receptor binding;Regimen;Resistance;Resistance development;resistance gene;resistance mechanism;resistant Klebsiella pneumoniae;Respiratory System;Role;Site;Superbug;synergism;System;Therapeutic;Time;Translating;Translations;treatment duration;Treatment Failure;Treatment Protocols;Urinary tract;Validation;World Health Organization

PROJECT_TITLE: Precise Combination Strategies Targeting Carbapenem-Resistant Klebsiella pneumoniae

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: LA JOLLA

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE This project aims to disseminate validated technologies and resources of the National Center for Microscopy and Imaging Research (NCMIR) at UC San Diego to hasten the completion of strategic goals of the BRAIN Initiative for unlocking the role of different cell types and producing maps of brain circuits and ultrastructure at multiple scales. NCMIR will provide specialized molecular probes, novel specimen preparation methods, leading- edge microscopy and imaging technologies, and scalable computational tools to help brain investigators traverse difficult to navigate spatial and temporal scales, deliver new insight into multiscale structure/function relationships, and provide a fundamental understanding of the macromolecular mechanisms underlying brain function.

PI_NAMEs: ELLISMAN, MARK H (contact)

PROGRAM_OFFICER_NAME: TRZCINSKI, NATALIE KATHERINE

PROJECT_TERMS: 3-Dimensional;Achievement;Actins;Animal Model;Behavior;Biomedical Technology;Brain;brain cell;Brain imaging;BRAIN initiative;Brain Mapping;brain research;brain tissue;cell type;Chemicals;Communities;Community Outreach;Complex;computerized tools;connectome;cost;cryogenics;cyber infrastructure;data acquisition;Data Analyses;data dissemination;data management;data sharing;deep learning;Disease;Electron Microscopy;Elements;Endoplasmic Reticulum;Extracellular Matrix;Face;Genetic;Goals;Histologic;Image;Imaging Device;imaging platform;Imaging Techniques;Imaging technology;In Situ;Information Technology;insight;instrument;instrumentation;interest;Investigation;Label;large scale data;Learning;Light;light microscopy;Maps;Measures;Methods;Microscopy;Mitochondria;Molecular;Molecular Probes;multimodal data;multimodality;nano;National Center for Research Resources;National Institute of General Medical Sciences;Nerve Tissue;neural;Neurons;Neurosciences;novel;operation;Physiological;Population;Preparation;preservation;Process;reconstruction;Recovery;Research;Research Personnel;Research Project Grants;Resolution;Resource Sharing;Resources;Roentgen Rays;Role;Sampling;Scanning Electron Microscopy;Shapes;spatiotemporal;Specimen;Stains;Structure;Subcellular Anatomy;success;synaptic function;Techniques;Technology;technology validation;tomography;tool;Training;Ultramicrotomy;Vertebral column;Vesicle;Visualization;voltage;way finding;Work;X ray microscopy

PROJECT_TITLE: National Center for Microscopy and Imaging Research: A BRAIN Technology Integration and Dissemination Resource


NIH_SPENDING_CATS: Brain Disorders;Neurosciences

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS SAN ANTONIO

PHR: The proposed experiments determine how local interconnections within the basal ganglia nuclei alter signal processing and oscillatory activity generated within the basal ganglia circuit. Local processing has previously not been taken into account in models of basal ganglia that are used to predict and evaluate potential treatments for Parkinson's disease. A next generation basal ganglia model incorporating this information may improve understanding of basal ganglia disorders and predictions of treatment effectiveness.

PI_NAMEs: WILSON, CHARLES J (contact)

PROGRAM_OFFICER_NAME: SIEBER, BETH-ANNE

PROJECT_TERMS: Anatomy;Basal Ganglia;Basal Ganglia Diseases;Cell Nucleus;cell type;Characteristics;Corpus striatum structure;design;Discontinuous Capillary;experimental study;Frequencies;Functional disorder;Ganglia;improved;infancy;Knowledge;Link;Modeling;Neurodegenerative Disorders;Neurons;next generation;optogenetics;Output;Parkinson Disease;Periodicals;Periodicity;Prediction of Response to Therapy;Predictive Value;Property;response;signal processing;Signal Transduction;Substantia nigra structure;Synapses;Therapeutic;therapy development;Treatment Effectiveness

PROJECT_TITLE: Oscillations and Resonance in Basal Ganglia Circuits


NIH_SPENDING_CATS: Brain Disorders;Congenital Structural Anomalies;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Pediatric;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: PROJECT NARRATIVE SCN3A neurodevelopmental disorder is a devastating condition caused by mutation of the gene SCN3A (which encodes the sodium channel subunit Nav1.3) and is defined by treatment-resistant epilepsy, severe/profound intellectual disability, and malformation of cortical development, the latter being a surprising consequence of dysfunction of an ion channel. The objective of this proposal, which employs cutting-edge tools and innovative technical approaches in newly-generated advanced model systems, is to investigate the pathogenic mechanisms that underlie epilepsy and brain malformation in SCN3A neurodevelopmental disorder. The long- term objective of this research is to (1) understand the normal role of Nav1.3 in the function of developing neurons and (2) advance from preclinical models to mechanistically oriented treatments or preventative therapies in human patients.

PI_NAMEs: GOLDBERG, ETHAN M (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Acceleration;Acute;Alleles;Anticonvulsants;Biological Models;biophysical properties;Biophysics;Birth;Brain;brain malformation;Calcium;Cell Line;Cells;Cerebral cortex;channel blockers;Chronic;Clinical;clinical application;clinical phenotype;cohort;Cortical Malformation;CRISPR correction;CRISPR/Cas technology;Data;Defect;Dependence;Development;Disease;Electrophysiology (science);Electroporation;Embryo;Epilepsy;Exhibits;experimental study;Functional disorder;gain of function;Gene Mutation;Genes;genetic variant;Genetic Variation;Heterozygote;Human;human disease;human induced pluripotent stem cells;Immunohistochemistry;Impairment;in utero;In Vitro;Inherited;innovation;Intellectual functioning disability;Ion Channel;Knock-in Mouse;Lead;Link;loss of function;LoxP-flanked allele;malformation in cortical development;Maps;Mediating;Membrane Potentials;migration;Modeling;Morphology;mouse model;Mus;mutant;Mutant Strains Mice;Neurites;Neurodevelopmental Disability;Neurodevelopmental Disorder;neuronal excitability;Neurons;Neurosciences;novel;novel therapeutics;overexpression;Pathogenicity;Pathologic;Pathology;patient derived induced pluripotent stem cells;Patients;pharmacologic;Pharmacology;Physiology;Placenta;postnatal;Pre-Clinical Model;pregnant;prevent;Prevention;Preventive measure;Preventive therapy;Property;Prosencephalon;pup;Registries;Research;Resistance;Role;severe intellectual disability;Severities;Severity of illness;Slice;Sodium;Sodium Channel;System;targeted treatment;Testing;Time;tool;Translating;Variant;variant of unknown significance;voltage;voltage clamp

PROJECT_TITLE: Pathomechanisms of SCN3A-related neurodevelopmental disorder

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ORG_CITY: PITTSBURGH

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Oxidative stress has been indicated as one of the most relevant causes of dopamine neuron degeneration in familial and idiopathic Parkinson disease (PD). The first part of the present proposal is designed to mechanistically identify the contribution in PD pathogenesis of the most represented NADPH oxidase isoforms in brain (1, 2, 4) in PD, focusing on specific key downstream pathogenic effects such as LRRK2 kinase activation, α-synuclein dysmetabolism, mitochondrial dysfunction and neuroinflammation. Based on our preliminary data, (not excluding possible implications of NOX1 and NOX4) we expect to address NOX2 as the most relevant pathogenic isoform and, in this contest, the proposed work will also provide evidence on the therapeutic potential of antisense oligonucleotide mediated NOX2 knock down in the brain of rat models of PD.

PI_NAMEs: DI MAIO, ROBERTO  (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Address;Affect;age related;alpha synuclein;Animal Disease Models;Antisense Oligonucleotides;Binding;Biological Assay;Biological Process;Brain;Cells;Complex;Consensus;Data;Defect;design;Detection;Disease;disease model;dopaminergic neuron;effective therapy;Electron Transport;Environment;Event;Experimental Designs;Experimental Models;Functional disorder;Genes;Histologic;Idiopathic Parkinson Disease;In Situ;Inflammatory Response;knock-down;Knock-out;Ligation;LRRK2 gene;Mediating;Microglia;Mitochondria;mitochondrial dysfunction;Modeling;Movement Disorders;NADP;NADPH Oxidase;Nature;Nerve Degeneration;Neuroglia;neuroinflammation;Neurons;neuroprotection;nigrostriatal degeneration;non-motor symptom;novel;novel drug class;novel therapeutic intervention;Outcome;overexpression;Oxidases;Oxidation-Reduction;oxidative damage;Oxidative Stress;Parkinson Disease;Parkinsonian Disorders;Pathogenesis;pathogenic isoform;Pathogenicity;Pathologic;Pathology;Patients;Persons;pharmacologic;Phosphotransferases;Play;Post-Translational Protein Processing;prevent;Printing;Process;Production;Protein Import;Protein Isoforms;Rattus;Reactive Oxygen Species;Regulatory Pathway;Reporting;Research;Resolution;response;Role;Rotenone;Signal Transduction;Source;Superoxides;System;Technology;Testing;Therapeutic;Time;United States;Work

PROJECT_TITLE: NADPH Oxidase 2 in Parkinson's Disease Pathogenesis

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


NIH_SPENDING_CATS: Neurosciences

PHR: PROJECT NARRATIVE  To study where and when plastic changes occur in the cortical motor areas to acquire and retain skilled sequential movements, we propose to manipulate information storage in primary motor cortex (M1) and dorsal premotor cortex (PMd) of non-human primates by injecting inhibitor for protein synthesis or DNA methylation into these areas. We will examine whether the neural trace for sequential movements is gradually consolidated in M1 with extended practice, whether learning processes in M1 and PMd operate in different time frames, and whether M1 and PMd become sites of long-term storage for the acquired sequential movements. The results will expand our understanding of the temporal evolution of the learning and provide information to develop new strategies for acquiring motor skills.

PI_NAMEs: OBAYASHI (OHBAYASHI), MACHIKO  (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Affect;Animals;Area;Behavior;Cues;Data;Decitabine;design;DNA Methylation;Dorsal;Elements;Evolution;experimental study;frontal lobe;Functional Magnetic Resonance Imaging;Funding;Gene Expression;Gene Expression Regulation;gray matter;Human;Information Storage;inhibitor;Injections;Learning;Learning Skill;Lesion;Maintenance;Memory;memory consolidation;Metabolic;Monkeys;Motor;Motor Cortex;Motor Neurons;Motor Skills;Movement;Nature;neural;Neurons;nonhuman primate;Performance;pharmacologic;Phase;Process;Protein Biosynthesis;Protein Synthesis Inhibition;Protein Synthesis Inhibitors;Recovery of Function;Rodent;sequence learning;Signal Transduction;Site;skills;Stroke;Synaptic plasticity;Testing;Time;Training;Traumatic Brain Injury;Visual;visual performance

PROJECT_TITLE: Motor Skill and the Cortical Motor Areas

STUDY_SECTION: SMN

STUDY_SECTION_NAME: Sensory-Motor Neuroscience Study Section[SMN]


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: Columbus

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE The goal of this project is the design, synthesis, and biological evaluation of novel bacterial topoisomerase inhibitors with activity against pathogens which threaten human health, such as methicillin-resistant Staphylococcus aureus (MRSA). Multidisciplinary studies involving microbiology, pharmacology, and structural biology will yield fundamental knowledge of the mechanisms of action and resistance of these compounds. These novel inhibitors will overcome previous limitations related to resistance, thereby greatly advancing this class of innovative antibacterials.

PI_NAMEs: MITTON-FRY, MARK J. (contact)

PROJECT_TERMS: Address;alkalinity;Amides;Amino Acid Substitution;analog;Anti-Bacterial Agents;Antimicrobial Resistance;Area;Bacteria;bacterial resistance;Binding;Biochemical;Biochemical Pharmacology;Biological;Biological Assay;Cardiovascular system;Cells;Chemicals;Clinical;clinical candidate;clinical development;Collection;computational chemistry;Coupled;design;Development;DNA;DNA Damage;DNA Double Strand Break;DNA Gyrase;DNA Topoisomerase IV;drug resistant bacteria;Drug Targeting;Ensure;Enzyme Inhibition;Enzymes;Evaluation;Exhibits;fitness;fluoroquinolone resistance;Genus staphylococcus;Goals;Growth;Health;Human;improved;In Vitro;in vivo;Infection;inhibitor;inhibitor therapy;innovation;insight;Kinetics;Knowledge;Label;Lead;lead candidate;lipophilicity;Measures;Metabolism;Methicillin Resistance;methicillin resistant Staphylococcus aureus;Microbiology;Minimum Inhibitory Concentration measurement;Modeling;Modification;Molecular;molecular dynamics;mortality;Multi-Drug Resistance;multidisciplinary;mutant;Mutation;novel;pathogen;Pathway interactions;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacology;Phase;phase II trial;Phase III Clinical Trials;Point Mutation;Positioning Attribute;Property;rational design;Refractory;Resistance;Resistance development;resistance frequency;resistance mutation;Resistance profile;resistant strain;Risk;Roentgen Rays;Safety;Series;SOS Response;Staphylococcus aureus;structural biology;Structural Models;Structure;success;Therapeutic;Time;tool;Topoisomerase Inhibitors;Topoisomerase-II Inhibitor

PROJECT_TITLE: Overcoming Resistance to Novel Bacterial Topoisomerase Inhibitors