NIH_SPENDING_CATS: Cancer

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PROJECT NARRATIVE The University of Minnesota Cancer Research, Education and Training Experience (CREATE) program is an immersive, integrated residential summer research experience that will train, motivate and prepare a diverse and talented group of undergraduate students to successfully pursue a biomedical research career. We aim to reduce cancer incidence, morbidity and mortality by developing the next generation of scientists and physician scientists who will develop new and more specific cancer therapies.

PI_NAMEs: SCHWERTFEGER, KATHRYN L;SHIMIZU, YOJI  (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Academic achievement;Acceleration;Accreditation;Address;Administrative Efficiency;Admission activity;Advisory Committees;Aging;anti-cancer research;Area;Biological Sciences;Biomedical Research;Cancer Biology;Cancer Center;Cancer Death Rates;Cancer Research Project;cancer therapy;career;Career Choice;Clinical;cohort;Complement;Comprehensive Cancer Center;Credentialing;Development;Doctor of Philosophy;education research;effectiveness evaluation;Elements;Evaluation;experience;Faculty;Feedback;fighting;Foundational Skills;Foundations;Funding;Goals;Group Meetings;improved;Incidence;Institution;interdisciplinary approach;interest;Interview;Laboratories;Learning;Letters;Malignant Neoplasms;Mathematics;matriculation;Measures;Medical;meetings;member;Mentors;Mentorship;Minnesota;Morbidity - disease rate;mortality;next generation;novel;Outcome;Participant;Persons;Physicians;programs;Puerto Rico;Qualifying;Recommendation;recruit;Recruitment Activity;Research;Research Personnel;Research Project Grants;Role;Science;Scientist;skills;student participation;Student recruitment;Students;success;summer research;Surveys;Talents;Training;Training and Education;Training Programs;undergraduate research experience;undergraduate student;Underrepresented Students;United States;United States National Institutes of Health;Universities;Work;Writing

PROJECT_TITLE: Cancer Research Education And Training Experience

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Institutional Training and Education Study Section (F)[NCI-F]


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: Clinical Research;Clinical Trials and Supportive Activities;Health Services;Kidney Disease;Patient Safety;Telehealth

ORG_CITY: PITTSBURGH

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Acute kidney injury (AKI) incidence in the US is estimated to be about 6.8/1000 population and contributes to the development or progression of chronic kidney disease, end-stage renal disease, cardiovascular symptoms, and death, not to mention recurrent AKI episodes and impaired health-related quality of life. Processes of care after AKI hospitalization have been found to be suboptimal, with lack of continuity of care, delayed follow-up and suboptimal medication management exacerbating the risks of adverse outcomes. Results from the COPE- AKI Consortium will lead to interventions to optimize processes of care and identify key pharmacologic and non-pharmacologic interventions to reduce morbidity among these high-risk patients.

PI_NAMEs: ABEBE, KALEAB Z (contact);FRIED, LINDA FAITH;KANE-GILL, SANDRA L;PALEVSKY, PAUL M

PROGRAM_OFFICER_NAME: GREER, RAQUEL CHARLES

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;Address;Adverse event;adverse outcome;Ambulatory Care;Biometry;cardiovascular risk factor;Cardiovascular system;care coordination;Caring;Cessation of life;Chronic Kidney Failure;Clinical;clinical center;Clinical Data;Clinical Trials;Clinical Trials Design;clinically relevant;Collaborations;Conduct Clinical Trials;Consensus;Continuity of Patient Care;Data;Data Analyses;Data Collection;Data Coordinating Center;data dissemination;data management;data quality;design;Development;Dialysis procedure;disability;Education;End stage renal failure;evidence base;experience;follow-up;Gills;Glucose;Goals;Health;health management;health related quality of life;high risk;hospital care;hospital readmission;Hospitalization;Hospitals;Impaired health;improved;Incidence;Information Dissemination;Injury to Kidney;Intervention;Kidney;Kidney Diseases;kidney dysfunction;Knowledge;Manuals;Measurement;Medical;Medication Management;Monitor;Morbidity - disease rate;multi-component intervention;multidisciplinary;Nonpharmacologic Therapy;Nurses;Online Systems;operation;Outcomes and Health Services Research;Participant;Patient Discharge;patient engagement;patient oriented;Patient Outcomes Assessments;Patient-Focused Outcomes;Patients;Persons;Pharmacists;pharmacologic;Phase;Population;primary outcome;Procedures;Process;process optimization;programs;protocol development;Protocols documentation;Randomized;readmission rates;Recording of previous events;Records;Recurrence;Renin-Angiotensin-Aldosterone System;Reporting;Research;Research Design;Risk;Risk Factors;Safety;satisfaction;Sodium;success;symporter;Symptoms;Syndrome;System;Technology;telehealth;Testing;treatment as usual;United States National Institutes of Health;Universities;virtual visit

PROJECT_TITLE: The Pittsburgh Scientific and Data Research Center for the COPE-AKI Consortium (Pitt-SDRC)


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Genetics;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: LA JOLLA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative Microglia are tissue macrophages that reside in the central nervous system (CNS) and perform unique and critical auxiliary functions important to CNS development, homeostasis, immunity and repair. Major unanswered questions include determining the combination of signals within the brain that trigger the differentiation of erythromyeloid progenitor (EMP) cells to become mature microglia and how alterations in these signals specify distinct microglia phenotypes in health and disease. The proposed studies are intended to qualitatively advance understanding of mechanisms that establish the brain environment dependent program of human microglia gene expression.

PI_NAMEs: GLASS, CHRISTOPHER K (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Address;Antisense Oligonucleotides;Automobile Driving;Autopsy;Biological Models;Brain;brain tissue;Cell Nucleus;cell type;Central Nervous System;Chemistry;Chromatin;Collaborations;Collection;Communities;Computing Methodologies;Data;Dependence;Development;Disease;Enhancers;Environment;Environmental Risk Factor;Epigenetic Process;Erythro;experimental study;Foundations;Freezing;Gene Expression;Genes;Genetic;Genetic Transcription;genetic variant;Goals;Grant;Health;Homeostasis;Human;human induced pluripotent stem cells;humanized mouse;Immunity;improved;In Vitro;in vivo;induced pluripotent stem cell;insight;Laboratories;loss of function;Macrophage;Mediating;Mediator;Methods;Microglia;Modeling;Molecular;Mus;Mutation;Myeloid Progenitor Cells;nervous system development;Nervous System Disorder;Neurosciences;nuclear factors of activated T-cells;Operative Surgical Procedures;overexpression;Pharmacologic Substance;Phenotype;Positioning Attribute;Process;programs;Quantitative Trait Loci;Regulation;Regulatory Element;repaired;Research Personnel;Resources;Role;Sampling;Signal Pathway;Signal Transduction;single cell sequencing;Sorting;Specific qualifier value;Statistical Methods;Technology;Testing;Tissues;transcription factor;Transcription Factor AP-1;transcriptome;transcriptomics

PROJECT_TITLE: Mechanisms controlling human microglia gene expression

STUDY_SECTION: CMBG

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


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: FORT COLLINS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: Narrative This project will investigate how Mycobacterium tuberculosis fine-tunes the structure of its major cell envelope (lipo)polysaccharides to adapt to its environment and cause infection.

PI_NAMEs: GONZALEZ-JUARRERO, MERCEDES ;JACKSON, MARY  (contact)

PROGRAM_OFFICER_NAME: ROBINSON, RICHARD THOMAS

PROJECT_TITLE: Tailoring modifications of polysaccharides in Mycobacterium tuberculosis

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


NIH_SPENDING_CATS: Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Conditions Affecting the Embryonic and Fetal Periods;Genetics;Human Genome;Maternal Health;Nutrition;Obesity;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative The study will assess the feasibility of improving the metabolic health of obese women, and their offspring, by implementing a relatively short, aggressive weight loss intervention. The study is also designed to find specific molecules in the blood of obese women that could be changed by diet or other approaches that could reduce the risk of their children becoming obese in childhood or even in adulthood.

PI_NAMEs: BURANT, CHARLES F (contact);DOLINOY, DANA ;PADMANABHAN, VASANTHA ;ROTHBERG, AMY ELIZABETH

PROGRAM_OFFICER_NAME: EVANS, MARY

PROJECT_TERMS: Adult;Affect;Air;Amino Acids;Birth;Birth Weight;Blood;Body Composition;Body mass index;Body Weight decreased;Cardiometabolic Disease;cardiometabolic risk;Child;Childhood;Chromatin Structure;Chronic Disease;Clinical;clinical phenotype;Collection;Computer Models;Conceptions;Confounding Factors (Epidemiology);Counseling;Cross-Sectional Studies;design;Development;Diabetes Mellitus;Diet;Disease;DNA Methylation;Environment;Environmental Exposure;Epigenetic Process;epigenome;epigenomics;experience;Exposure to;Factor Analysis;fetal;fetal adiposity;Fetal Development;Fetal Growth;First Pregnancy Trimester;Gene Expression;Genes;Genetic;Genome;Gestational Diabetes;gestational weight gain;Health;Heart Diseases;High birth weight infant;histone modification;Human;Hybrids;Hypertension;improved;in utero;indexing;Infant;infant outcome;Inflammation;Inflammatory;inflammatory marker;Institutional Review Boards;Intervention;intrauterine environment;Leukocytes;lipidomics;Lipids;Literature;Lymphocyte;Maternal complication;maternal obesity;maternal outcome;Measures;Mediating;Medical;Messenger RNA;Metabolic;Metabolism;metabolome;metabolomics;Methylation;methylation pattern;methylome;Michigan;Modeling;Molecular;molecular phenotype;Molecular Profiling;Mothers;Multivariate Analysis;Neonatal;neonate;Newborn Infant;Non obese;Nutrient;nutrition;Nutritional;obese mothers;Obesity;obesity in children;obesity in pregnancy;obesity risk;Observational Study;offspring;Outcome;Overweight;Pathway interactions;Phenotype;Physiological;Pisum sativum;Plasma;Plethysmography;Pregnancy;Pregnancy Complications;Pregnant Women;prepregnancy;programs;prospective;Proteome;Proteomics;Randomized;recruit;Regression Analysis;Resources;response;Risk;Risk Marker;Risk Reduction;Rodent;Sampling;Second Pregnancy Trimester;standard of care;success;Testing;Thinness;transcriptome sequencing;ultrasound;Umbilical Cord Blood;Universities;Weight;weight loss intervention;Woman;Women's Group

PROJECT_TITLE: Maternal metabolic and molecular changes induced by preconception weight loss and their effects on birth outcomes

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


ADMINISTERING_IC: GM

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRACTIVE Bacterial cells growing on the surfaces of human tissues are often sources of chronic infections. This project will define mechanisms used by bacteria to grow on solid surfaces with the long- term goal of inhibiting colonization of human tissues by bacterial pathogens.

PI_NAMEs: HERSHEY, DAVID M. (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Bacteria;Bacterial Infections;Caulobacter crescentus;Cell Cycle Progression;Cell Physiology;Cells;Characteristics;Chemotaxis;chronic infection;Data;Development;Genes;Genetic;Genetic Screening;Goals;Health;human tissue;Infection;insight;Laboratories;Link;Lung;mechanotransduction;Modeling;Molecular Machines;novel;Oral cavity;pathogenic bacteria;Physiological;response;Skin;Solid;Source;Surface;System;Therapeutic Intervention;therapeutic target;Tissues;Work

PROJECT_TITLE: Surface adaptation in bacterial cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-C(55)R]


ADMINISTERING_IC: HD

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

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

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Services;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Pediatric;Pregnancy;Prevention;Women's Health Research

ORG_CITY: PROVIDENCE

ORG_NAME: MIRIAM HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE Women with histories of trauma express unique, under-recognized concerns and fears of prenatal care and birth and are at high risk for developing pregnancy complications and perinatal mental health conditions. Therefore, obstetric clinicians need practical evidence-based training and effective tools to meet the needs of pregnant women who have survived trauma without causing further harm in clinical encounters. The proposed study uses an implementation science framework to develop an intervention toolkit that effectively empowers clinicians to integrate trauma-informed approaches into obstetric practice with all patients.

PI_NAMEs: WARD, LAURA G (contact)

PROGRAM_OFFICER_NAME: MITCHELL, MEGAN S

PROJECT_TERMS: Address;Adherence;Administrator;Adopted;Adoption;American College of Obstetricians and Gynecologists;Anxiety;Appointment;Attitude;Behavior Therapy;Behavioral Medicine;Birth;Breast Feeding;career;Caring;Cervical;child bearing;Clinic;Clinical;clinical encounter;Collaborations;Communities;cost effective;Data;Development;Discipline of obstetrics;Disclosure;Discrimination;Dissociation;Distress;Educational workshop;effectiveness/implementation trial;electronic medical record tool;Elements;empowerment;Environment;Environmental Risk Factor;evidence base;Evidence based intervention;experience;Feeling;Feeling suicidal;formative assessment;Fright;Funding;Future;Goals;Health;health administration;Healthcare;high risk;Hospitals;implementation evaluation;implementation framework;implementation outcomes;implementation science;implementation strategy;implementation trial;improved;Individual;Infant;Infant Health;innovation;Intervention;Interview;knowledge base;Mental Health;Mentored Patient-Oriented Research Career Development Award;Mentorship;Methodology;Methods;National Institute of Child Health and Human Development;novel;Nurses;obstetric care;obstetric outcomes;Outcome;Outpatients;Patient Education;Patients;Pelvic Pain;Perception;Perinatal;Perinatal Care;perinatal health;perinatal mental health;perinatal outcomes;Perinatology;peripartum depression;Personal Satisfaction;Physicians;pilot test;pilot trial;Population;post pregnancy;Post-Traumatic Stress Disorders;postpartum care;Postpartum Period;preference;Pregnancy;Pregnancy Complications;pregnancy hypertension;pregnant;Pregnant Women;premature;Premature Labor;Prenatal care;Procedures;Process;Proctor framework;professor;promote resilience;Protocols documentation;Provider;provider factors;psychological trauma;Qualitative Research;Randomized, Controlled Trials;Recommendation;Recording of previous events;Replicating Effective Programs;Reporting;Research;Research Methodology;Research Personnel;Resources;response;Risk;Safety;scale up;Scientist;screening;Screening procedure;Service setting;skills;Stress;Substance abuse problem;Survivors;Testing;therapy development;Time;tool;Training;Trauma;trauma care;Treatment Protocols;United States Substance Abuse and Mental Health Services Administration;Universities;Violence;White Women;Woman;women of color;Women's Health;working group

PROJECT_TITLE: Trauma-Informed Obstetric Care:  Development and Implementation of a Stakeholder-Informed Toolkit for Obstetric Providers and Patients

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Obstetrics and Maternal-Fetal Biology Study Section[CHHD-B]


NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biotechnology;Digestive Diseases;Inflammatory Bowel Disease;Nanotechnology

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Despite advances in available treatment, achieving mucosal healing remains challenging for many patients suffering from inflammatory bowel disease (IBD). In this proposal, we will engineer a biomaterial-based biomimetic system that can selectively target the inflamed mucosa and locally release therapeutics to the damaged epithelium. The proposed research will use innovative approaches that employ drug delivery not only mimicking the mucus layer, but also as a tool to interrogate epithelial repair at the site of mucosal inflammation to shed light on mechanisms of mucosal healing for IBD and many other mucosal barrier disorders.

PI_NAMEs: ZHANG, SUFENG  (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Address;Bacteria;Bacterial Translocation;Biocompatible Materials;Biomimetic Materials;Biomimetics;Biopsy;Categories;Cells;Charge;chemically induced colitis;Chemicals;Chronic;Clinical Trials;Colitis;Colon;combinatorial;Complex;Development;Disease;Disease remission;Drug Combinations;Drug Delivery Systems;drug efficacy;Engineering;Epidermal Growth Factor;Epithelial Cells;epithelial repair;Epithelium;epithelium regeneration;evidence base;Gastrointestinal tract structure;Gel;Gene Expression Profiling;Goals;gut inflammation;healing;Histology;Hydrogels;Immune response;Immune system;immunoregulation;improved;In Situ;in vivo;Inflammation;Inflammation Process;Inflammatory Bowel Diseases;innovation;Interleukin-10;intestinal epithelium;intestinal homeostasis;Intestinal Mucosa;Intestinal permeability;Invaded;Lamina Propria;Measures;Mediating;Mediator;microbiota;Mucins;mucosal site;Mucositis;Mucous body substance;Mucous Membrane;murine colitis;Mus;nanoparticle;nanoparticle drug;Normal tissue morphology;novel strategies;Outcome;Pathogenicity;Patients;Permeability;Pharmaceutical Preparations;Polymers;Pre-Clinical Model;premature;prevent;primary endpoint;Process;protein expression;Proteins;Regulatory T-Lymphocyte;repaired;Research;restoration;Ribosomal RNA;Rodent Model;Severities;Signal Transduction;Site;success;System;targeted treatment;Therapeutic;Tissues;tool;Treatment Efficacy;Ulcer;Vancomycin

PROJECT_TITLE: Engineered biomimetic materials for intestinal mucosal healing

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


NIH_SPENDING_CATS: Diabetes

ORG_CITY: RIVERSIDE

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: PROJECT NARRATIVE The overall objective of this proposal is to achieve fundamental understanding of protein activities that are impacted by abnormal ganglioside expression and to investigate the linkage of such abnormality to diseases such as cancer and diabetes. The research aims to identify key factors that influence complex ganglioside-protein interactions with a new technology platform. The results will provide molecular basis for effective search of anti-cancer and diabetes therapeutics.

PI_NAMEs: CHENG, QUAN JASON (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Affinity;Anabolism;anti-cancer;anti-cancer therapeutic;Binding;Biochemical;Biological;Biomimetics;Biophysics;Blood Cells;Bypass;Carbohydrates;caveolin 1;Cell Adhesion;Cell Communication;Cell membrane;Cell Physiology;Cells;Complex;Development;Diabetes Mellitus;Disease;EGF gene;Environment;Epidermal Growth Factor Receptor;Epithelial Cells;Event;Family;Gangliosides;Glycocalyx;Glycolipids;Glycoproteins;Glycosphingolipids;glycosyltransferase;Goals;Head;Human body;Immune;Individual;Inflammation;Insulin;Insulin Receptor;Insulin Resistance;Investigation;KDR gene;Killer Cells;Libraries;Link;Lipid Bilayers;Lipids;Malignant Neoplasms;Mediating;Membrane;Membrane Microdomains;Membrane Proteins;Modeling;Molecular;Nerve Regeneration;Neurons;neuroregulation;new technology;Non-Insulin-Dependent Diabetes Mellitus;novel;Pathology;Pattern;Play;Polysaccharides;Property;protein function;Proteins;receptor;Research;Role;Series;Sialic Acids;Sialyltransferases;Signal Pathway;Signal Transduction;Spectrum Analysis;Structure;Structure-Activity Relationship;Surface;Surface Plasmon Resonance;System;Techniques;technology platform;Therapeutic;therapeutic target;Toxic effect;tumor;tumor progression;Variant;Vascular Endothelial Growth Factors

PROJECT_TITLE: Glycolipid biointerface to decipher disease-implicated ganglioside-protein interactions

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Nutrition;Obesity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: NARRATIVE Obesity is one of the largest public health challenges, with stark disparities across racial/ethnic and socioeconomic classifications. This research proposal will identify the epigenomic changes that link socioeconomically adverse life circumstances to obesity and cardiovascular disease in a racially/ethnically diverse sample. Our research team has years of collective experience in epidemiology and health disparities research, which we will put to use in our proposed study of how social exposures and biology interact to impact obesity and cardiovascular disease in diverse populations.

PI_NAMEs: FERNANDEZ-RHODES, LINDSAY  (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: Adult;adult obesity;Affect;African American;African American population;Atherosclerosis Risk in Communities;Biological;Biological Process;Biology;Biosocial;blood pressure elevation;Body mass index;burden of illness;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;Central obesity;Classification;Clinical;cohort;Cohort Studies;Complex;Cytosine;Data;Data Analyses;disease disparity;Disease Outcome;disorder risk;Disparity;DNA Methylation;Dyslipidemias;Economic Burden;Education;Environment;Epidemiology;Epigenetic Process;epigenomics;ethnic disparity;ethnic diversity;ethnic minority;Ethnic Origin;Ethnic Population;Etiology;European;Event;experience;Functional disorder;Funding;Gene Expression;Genes;Genetic;Genetic Variation;Genomics;Grant;Guanine;Health Disparities Research;health disparity;Heterogeneity;Hispanic;Impairment;improved;Income;Individual;Inflammation;innovation;inorganic phosphate;Intervention;Investigation;Jackson Heart Study;Japanese American;Latino;Learning;Life;Life Cycle Stages;Life Experience;Link;Measures;Mediating;Metabolic;Methylation;Minority;Modeling;multi-ethnic;National Heart, Lung, and Blood Institute;Native Hawaiian;new therapeutic target;novel;novel marker;Obesity;Obesity Epidemic;obesity risk;Occupational Status;Occupations;Pathway interactions;pharmacologic;Phenotype;Population;population health;Population Heterogeneity;Prevalence;Public Health;Race;racial disparity;racial diversity;racial minority;racial population;Reporting;Research;Research Proposals;Risk;Risk Factors;Role;Sampling;sex;Shapes;Site;Skin;social;social determinants;socioeconomic adversity;Socioeconomic Status;socioeconomics;Source;study population;Surveys;Techniques;Testing;Time;Translating;United States National Institutes of Health;Women's Health;Work

PROJECT_TITLE: Bio-Social Pathways Linking Socioeconomic Adversity to Obesity

STUDY_SECTION: KEDD

STUDY_SECTION_NAME: Kidney Endocrine and Digestive Disorders Study Section[KEDD]


ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE TRPM3, a calcium-permeable nonselective cation channel, plays a key role in pain perception in somatosensory neurons, and inhibition of TRPM3 in pain models showed analgesic effects in mice, highlighting TRPM3 as a potential target for novel pain medications. This research project will focus on determining the first molecular structures of TRPM3 and elucidating the gating mechanism and pharmacology, taking advantage of single- particle cryo-EM and electrophysiological recording. The proposed research is relevant to public health and NIH’s mission, because the work will provide a deep understanding and knowledge of the relationships between atomic structure, function, and pharmacology of the nociceptor channel TRPM3, as well as a foundation for developing new drugs for the treatment of chronic pain.

PI_NAMEs: DU, JUAN  (contact)

PROJECT_TERMS: 3-Dimensional;Action Potentials;Afferent Neurons;Affinity;Affinity Chromatography;Analgesics;Antibodies;Architecture;Binding;Binding Proteins;Binding Sites;Biochemical;Brain;Calcium;Canis familiaris;Cations;Cell membrane;chemical association;Chemicals;chronic pain management;comorbidity;Complex;CRISPR/Cas technology;Cryoelectron Microscopy;Data;desensitization;Detection;Detergents;Development;Disease;Dose;Electrophysiology (science);Ensure;Environment;Epilepsy;epileptic encephalopathies;Epitopes;experimental study;Fire - disasters;Foundations;G-Protein-Coupled Receptors;Genes;Glucose;GTP-Binding Proteins;Human;Inflammatory;inhibitor;Injury;Insulin;Intellectual functioning disability;Ion Channel;Ions;Knock-in;Knowledge;Length;Letters;Ligand Binding;Ligands;Lipids;Mediating;Medical;Membrane Proteins;Miconazole;Mission;Molecular;Molecular Mechanisms of Action;Molecular Structure;Monoclonal Antibodies;Mus;nanodisk;Negative Staining;Neurons;neurosteroids;Nociceptors;novel;novel therapeutics;Outcome;Pain;pain model;pain perception;pain sensation;particle;patch clamp;Pathologic;Pathway interactions;Peripheral;Permeability;Pharmaceutical Preparations;pharmacologic;Pharmacology;Pharmacotherapy;Physiological;Play;pregnenolone sulfate;pressure;Primidone;Property;Protein Biochemistry;protein complex;protein purification;protein structure;Proteins;Protocols documentation;Public Health;receptor;Recombinant Proteins;Recombinants;Research;Research Project Grants;Resolution;response;Role;sensor;Sensory;Signal Pathway;small molecule;Solid;somatosensory;Source;Stimulus;stoichiometry;Structure;Structure of beta Cell of islet;success;System;Temperature;Therapeutic;Thermal Hyperalgesias;Tissues;Transgenic Mice;TRP channel;TRPV1 gene;United States National Institutes of Health;Work

PROJECT_TITLE: Structural Basis of Nociceptor Channel TRPM3 gating and pharmacology

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Machine Learning and Artificial Intelligence;Neurosciences

ORG_CITY: CHAMPAIGN

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Project Narrative This proposed research project will integrate the disruptive high-performance 3D CZT imaging-spectrometer technologies with a novel synthetic compound eye (SCE) camera design, as well as an innovative iterative image reconstruction method using deep-learning based priors, to develop a next-generation clinical brain SPECT imaging system with transformative spatial resolution and imaging sensitivity unattainable previously. The long- term objective is to apply this innovative imaging system to human brain SPECT studies using a collection of various SPECT radiotracers, and develop and advance physiological parametric imaging methodologies, in order to investigate the long-standing issues in neurobiology and improve our understanding of the interplay and relationship among cerebral blood flow and perfusion, brain tissue oxygenation, neuronal cell metabolism, and brain cell tracking under different cognitive challenges and biophysical conditions in healthy and in disease. We would envision the proposed system to serve as a unique imaging platform to significantly advance our understanding of neural cell biology and regional brain functions in response to various cognitive, behavioral, and physiological challenges by employing these unprecedentedly innovative SPECT imaging methodologies in order to assess all relevant quantitative physiological measurements that will be interpreted in an integrated fashion and synergistically so that new perspectives in brain research unattainable previously can be formulated.

PI_NAMEs: MENG, LING-JIAN  (contact);METZLER, SCOTT DEAN

PROGRAM_OFFICER_NAME: WANG, SHUMIN

PROJECT_TERMS: 3-Dimensional;Address;Advanced Development;animal imaging;Area;Attention;Behavioral;Biophysics;blood perfusion;Brain;brain cell;Brain imaging;Brain region;brain research;brain tissue;Cellular biology;Cerebrovascular Circulation;Characteristics;Clinical;Cognitive;Collection;commercial prototype;Communities;compound eye;Computer software;computerized data processing;Coupled;data acquisition;DCNU;deep learning;design;detection platform;detector;Devices;Disease;Electronics;Ensure;Evaluation;experimental study;fabrication;Helmet;Human;Image;image reconstruction;imaging capabilities;imaging platform;imaging study;imaging system;improved;Industrialization;innovation;Isotopes;Label;Measurement;Methodology;Methods;Microscopic;Modeling;Nature;Neurobiology;neuronal metabolism;Neurons;next generation;Noise;novel;parametric imaging;Performance;Photons;Physiological;prototype;Radioisotopes;radiotracer;Research;Research Project Grants;Resolution;response;sensor;Shapes;single photon emission computed tomography;spectrograph;Starvation;synthetic construct;System;Techniques;Technology;Time;tissue oxygenation;Tracer;Translating;ultra high resolution;uptake;Visualization;Width;Work

PROJECT_TITLE: 1 mm resolution single-photon spectral imaging of the brain


ORG_CITY: KANSAS CITY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE The proposed work seeks to understand the mechanism of protein conformational switching on membrane interfaces, a fundamental and unanswered question in cell biology that is crucial for proper cellular functions and of major relevance to cancer therapy. Using a battery of complementary experimental and computational approaches, we aim to characterize the interplay of lipid properties, pH, and divalent cations in modulating the tumor-targeting action of the pH Low Insertion Peptide (pHLIP). We will also refine and advance sequence-based prediction of protein-membrane interactions. The results of the proposed studies will be instrumental in the development of molecular platforms for cell-selective targeting and to advance therapeutic strategies.

PI_NAMEs: LADOKHIN, ALEXEY  (contact);THEVENIN, DAMIEN ;TOBIAS, DOUGLAS J

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Address;Affect;Amino Acids;Apoptosis;Apoptotic;Bacterial Toxins;Bacteriophages;Base Sequence;BCL2 gene;Behavior;cancer cell;cancer therapy;Cell membrane;Cell Physiology;Cells;Cellular biology;Cellular Membrane;Charge;Cholesterol;Circular Dichroism;Collaborations;Complex;Coupled;Data;design;Development;Divalent Cations;Drug Targeting;Environment;experimental study;Family;Fluorescence;Goals;Health;Human;improved;Individual;insight;interfacial;Ions;Knowledge;Letters;Lipid Bilayers;Lipids;Liquid substance;macromolecule;Malignant Neoplasms;Mammalian Cell;Measurement;Measures;Membrane;Membrane Lipids;membrane model;Membrane Proteins;Modeling;Molecular;Molecular Conformation;molecular dynamics;molecular modeling;monomer;NMR Spectroscopy;novel;Organelles;Outcome;Pathogenicity;Peptides;Physiological;Play;Process;Property;Protein Conformation;Protein Family;protein structure;Proteins;protonation;Protons;Publications;Regulation;Role;Structure;System;Testing;Therapeutic;Thermodynamics;Tissues;tool;tumor;United States National Institutes of Health;Variant;Vesicle;Water;Work

PROJECT_TITLE: Elucidating the Molecular Mechanisms of Conformational Switching during Protein Insertion into Membranes


NIH_SPENDING_CATS: Bioengineering;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_DEPT: NEUROSCIENCES

ORG_NAME: BROWN UNIVERSITY

PHR: HNN DISSEMINATION NARRATIVE This project supports the continued dissemination of a software tool (Human Neocortical Neurosolver, HNN) that allows researchers to develop and test hypotheses on the cellular and circuit level origin of human magneto- and electro-encephalography. A key value of HNN is to connect functionally-relevant human signals to circuit level dynamics studied in animal models, including data from revolutionary genetic and imaging tools used in mice and monkeys. Insights gained from the dissemination tool will be helpful in understanding the underpinnings of neurological and psychiatric diseases, such as Alzheimer’s disease, pain, depression, autism and schizophrenia.

PI_NAMEs: JONES, STEPHANIE RUGGIANO (contact)

PROGRAM_OFFICER_NAME: TRZCINSKI, NATALIE KATHERINE

PROJECT_TERMS: Address;Adopted;Adoption;Alzheimer's Disease;Animal Model;application programming interface;Area;autism spectrum disorder;base;Basic Science;Biophysics;Brain;BRAIN initiative;Calcium;Clinical Research;Code;code development;Collaborations;Communities;Complement;Complex;Computer software;Consultations;Data;design;Development;Disease;Documentation;Educational process of instructing;Educational workshop;Electroencephalography;Electrophysiology (science);Ensure;FAIR principles;Fee-for-Service Plans;Feedback;Fostering;Frequencies;Funding;Genetic;Goals;graphical user interface;Growth;Guidelines;hackathon;Health;Human;Image;Imaging Device;information processing;innovative technologies;insight;Letters;Link;Maintenance;Mental Depression;Mental disorders;Methods;Modeling;Monkeys;Mus;neocortical;Nervous System Disorder;neural;neural model;Neurons;neuropathology;Neurosciences;open source;Pain;Parameter Estimation;Physics;program dissemination;Publishing;Pythons;Reproducibility;Research Personnel;response;Running;Schizophrenia;scripting interface;Sensory;Service delivery model;Signal Transduction;simulation;Software Design;software development;Software Tools;Source;Standardization;success;supercomputer;Techniques;Testing;tool;Training;translational neuroscience;Update;user-friendly;Validation;voltage;Work;Writing

PROJECT_TITLE: Dissemination of the Human Neocortical Neurosolver (HNN) software for circuit level interpretation of human MEG/EEG


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Skin Cancer

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE  Epitranscriptomics, which details the functional and regulatory roles of RNA modifications, is an emerging mechanism of tumorigenesis and further studies into this field may unveil potential novel, druggable targets that will lead to the development of more effective cancer therapies. The F99 phase of this proposal will establish the mechanism by which ALKBH1 regulates mRNA m6A methylation and arsenic-induced skin tumorigenicity and may characterize ALKBH1 and/or its targets as therapeutic targets for arsenic-induced skin cancer. The K00 phase of this proposal will profile the dynamic role of m6A methylation throughout the process of malignant transformation and will identify novel m6A-dependent therapeutic targets or biomarkers that underlie the transition from non-transformed cell to transformed, tumorigenic cell.

PI_NAMEs: WILKINSON, EMMA ANNE (contact)

PROGRAM_OFFICER_NAME: ELJANNE, MARIAM

PROJECT_TERMS: Arsenic;arsenic carcinogenesis;Biology;cancer biomarkers;cancer therapy;cancer type;Carcinogen exposure;carcinogenicity;Carcinoma;career;Cause of Death;cell transformation;cell type;Cells;Chemicals;Chronic;contaminated drinking water;Data;Death Rate;demethylation;Development;Dioxygenases;Disease;druggable target;epitranscriptome;epitranscriptomics;Exposure to;Family;Funding;Gene Expression;Gene Expression Regulation;Gene Targeting;Genetic;Goals;In Vitro;in vitro Model;in vivo;insight;Investigation;keratinocyte;knock-down;Knowledge;Longitudinal Studies;Lung;Malignant - descriptor;Malignant Neoplasms;Mediating;member;Messenger RNA;Methylation;Modeling;Modification;Molecular;new therapeutic target;Normal Cell;novel;novel therapeutic intervention;novel therapeutics;Pathogenesis;Phase;Postdoctoral Fellow;posttranscriptional;potential biomarker;Primary carcinoma of the liver cells;Process;Regulation;Research;Research Personnel;Research Project Grants;RNA;RNA immunoprecipitation sequencing;RNA metabolism;Role;Running;Skin;Skin Cancer;Skin tumorigenesis;targeted biomarker;targeted cancer therapy;targeted treatment;Testing;Therapeutic;therapeutic biomarker;therapeutic target;Time;Transcript;transcriptome;Translating;tumorigenesis;tumorigenic;Tumorigenicity;United States National Institutes of Health;Work

PROJECT_TITLE: Elucidating the role of mRNA m6A methylation in tumorigenesis


NIH_SPENDING_CATS: Breast Cancer;Cancer;Digestive Diseases;Liver Disease;Maternal Health;Maternal Morbidity and Mortality;Women's Health Research

ORG_CITY: PORTLAND

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE To date there is no standard of care treatment for liver metastasis. Little is known about the role of liver fibroblasts in the liver pre-metastatic niche. This project will investigate the unique roles of liver fibroblasts in two distinct pre-metastatic niches: 1) liver fibroblasts during tissue remodeling that occurs during the postpartum period (liver involution) to better understand the increased liver metastasis observed in postpartum breast cancer, and 2) changes to liver fibroblast antigen presentation during pre-metastatic niche education of breast and pancreatic cancer.

PI_NAMEs: OZAKI, MICHELLE KAYOKO (contact)

PROJECT_TERMS: 3-Dimensional;Address;Affinity;Age;Antigen Presentation;Breast Cancer Cell;breast cancer diagnosis;Breast Cancer Education;breast cancer metastasis;Breast Cancer Patient;cancer cell;career;cell growth;Cell Separation;Cells;Childbirth;Coculture Techniques;Cues;cytokine;Data;Data Analyses;Deposition;Diagnosis;Disease;Distant;Education;effective therapy;Environment;Equation;Extracellular Matrix;Fibroblasts;Functional disorder;Gene Expression Profile;Growth Factor;Heterogeneity;Human;human data;Immune;Immune System Diseases;Immune Tolerance;Immunohistochemistry;In Vitro;in vivo;insight;Knowledge;Laboratory Finding;Lactation;Liver;Liver Fibrosis;Malignant Breast Neoplasm;Malignant neoplasm of pancreas;Malignant Neoplasms;Mammary gland;Mammary Neoplasms;Mediating;Metastatic Neoplasm to the Liver;Modeling;Mus;Neoplasm Circulating Cells;Neoplasm Metastasis;neoplastic cell;new therapeutic target;Nulliparity;Pathologic;Patients;Phase;Platelet-Derived Growth Factor alpha Receptor;Population;postpartum breast cancer;Postpartum Period;Pregnancy;pregnant;prevent;Primary Neoplasm;Process;Production;Prognosis;Proteins;Reporting;reproductive;Research Personnel;Research Project Grants;Research Training;response;Risk;Rodent;Rodent Model;Role;single-cell RNA sequencing;skills;standard of care;Stromal Cells;Survival Rate;Testing;Tissue Expansion;Tissues;transcriptional reprogramming;transcriptome sequencing;tumor;tumor growth;tumor immunology;tumor microenvironment;tumor progression;Tumor Promotion;Weaning;Woman;wound healing;young woman

PROJECT_TITLE: Fibroblasts in the establishment of the liver pre-metastatic niche


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Clinical Research;Eczema / Atopic Dermatitis;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: PHILADELPHIA

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Atopic children impact anxiety while among Mutations barrier little including further genetic understanding and Dermatitis (AD) i s chronic, inflammatory skin disease that is highly prevalent in both and adults and is associated with marked morbidity and disease burden due to the of symptoms, such as intense itch and sleep loss, increase prevalence of depression, and suicidal ideation, increased risk of comorbid disease and high economic cost, and the cause of AD remains to be fully elucidated, it is clear that it involves an interplay genetics, skin barrier defects, immune dysregulation and environmental factors.  in the FLG gene which ultimately produces Filaggrin, a critical component of the skin in humans, are associated with more severe AD disease primarily among Europeans, yet is known about the association between FLG variants and AD among other populations, admixed populations such as Latinx. Investigation of these aims would allow us to describe the genotypic characteristics of AD i n t his roup, help us better understand how ancestry and sociocultural factors contribute to risk for AD and gained a more robust of the pathogenesis of this disease which could then lead to novel prevention management strategies for populations at higher risk. a g

PI_NAMEs: CHIESA FUXENCH, ZELMA CHARLOTTE (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Acute Disease;Adult;African American population;African ancestry;Anxiety;Asian ancestry;Atopic Dermatitis;Award;Biology;Biometry;Board Certification;burden of illness;Candidate Disease Gene;care systems;career;career development;Characteristics;Child;Chromosome 1;Chronic;Clinical;Clinical Research;cohort;Collaborations;comorbidity;Complex;Data;Defect;Dermatitis;Dermatologist;Dermatology;Development;Development Plans;Diagnosis;Diagnostic;Disease;Disease susceptibility;disorder risk;Doctor of Medicine;Doctor of Philosophy;early onset;economic cost;Environment;Environmental Risk Factor;Epidemiology;ethnic minority;Ethnic Origin;Etiology;European;European ancestry;experience;Feeling suicidal;filaggrin;Flare;Foundations;Functional disorder;Funding;Future;gene environment interaction;Gene Mutation;Genes;Genetic;genetic epidemiology;genetic risk factor;genetic variant;Genetic Variation;Genomics;Genotype;Goals;Health Care Costs;health equity;Health system;high risk;High-Throughput Nucleotide Sequencing;Human;Immune;Immunologic Factors;improved;Individual;Inflammatory;Informatics;Institution;Investigation;Knowledge;Latinx;Latinx population;loss of function;loss of function mutation;Master of Science;medical schools;Mental Depression;Mentors;Mentorship;Mexican;microfluidic technology;Morbidity - disease rate;Mutation;Native Americans;next generation;novel;Onset of illness;Pathogenesis;Pathogenicity;Patient Care;patient oriented;Patients;Pennsylvania;Population;population based;Prevalence;Prevention;Prevention strategy;Production;professor;Proteins;Pruritus;Puerto Rican;Quality of life;Race;Research;research and development;Research Personnel;Residencies;Resources;Risk;Scientist;Series;Severities;Severity of illness;skills;Skin;skin barrier;skin disorder;Sleep Deprivation;social culture;sociocultural determinant;Statistical Methods;stratum corneum basic protein precursor;Susceptibility Gene;Symptoms;Therapeutic;Time;Training;United States;Universities;Variant;Work

PROJECT_TITLE: Investigation of Filaggrin Gene Mutations among Latinx patients with Atopic Dermatitis

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Social Determinants of Health

ORG_CITY: FLUSHING

ORG_NAME: QUEENS COLLEGE

ORG_STATE: NY

PHR: Public Health Relevance We will examine the roles of prenatal Superstorm Sandy stress, postnatal family environment, and COVID-19 pandemic stress on the trajectory of neural adaptation and neurobehavioral development, in an intact cohort of mother/offspring pairs, whom we have followed since pregnancy. The study will help us chart the course of developmental psychopathology from in utero to pre/puberty and determine whether intervention could preempt early-onset developmental psychopathology.

PI_NAMEs: NOMURA, YOKO  (contact)

PROGRAM_OFFICER_NAME: ZEHR, JULIA L

PROJECT_TERMS: Acceleration;Adolescence;Adolescent;Age;Aggressive behavior;Amygdaloid structure;Anxiety;Area;Back;Behavior;behavior measurement;Behavioral;behavioral outcome;behavioral phenotyping;Behavioral Symptoms;Biological;Birth;boys;Brain;Buffers;Child;Child Rearing;Childhood;childhood adversity;Clinical;Cluster Analysis;cognitive control;cohort;comorbidity;comparison control;Complement;COVID-19;COVID-19 pandemic;Data Collection;Data Set;Development;Developmental Course;Diagnostic;Diffusion;Disease;Disruptive Behavior Disorder;early adolescence;early onset;Emotional;Environment;Etiology;Exposure to;Face;Family;fetal;fetal programming;follow up assessment;Fright;girls;Goals;gray matter;Growth;Hair;hazard;high risk;Hippocampus;in utero;indexing;Individual;Individual Differences;Intervention;Interview;Life;Link;longitudinal analysis;low socioeconomic status;Measurable;Measures;Mediating;Mental Depression;Mental Health;Minority;Modeling;Mothers;Multimodal Imaging;National Institute of Mental Health;Natural Disasters;Natural experiment;Nature;Negative Valence;neural;neuroadaptation;neurobehavior;neurobehavioral;neuroimaging;neuromechanism;New York;offspring;Organ;Outcome;pandemic disease;pandemic impact;pandemic stress;Participant;Phenotype;Population;Positioning Attribute;postnatal;predictive modeling;preempt;Pregnancy;Pregnant Women;prenatal;prenatal exposure;prenatal influence;prenatal stress;Preparation;prospective;Protocols documentation;Psychopathology;psychosocial;Psychosocial Stress;Puberty;public health relevance;Quasi-experiment;Race;Random Allocation;random forest;Randomized;rate of change;recruit;Regulation;repository;Research Domain Criteria;response;Rest;Risk;Role;Sampling;sex;Sex Differences;sexual dimorphism;Signal Transduction;socioeconomics;Source;Specimen;Stress;stressor;Structure;substance use;Surface;symptomatology;Symptoms;System;Testing;Thick;Time;United States National Institutes of Health;white matter;Work

PROJECT_TITLE: The Evolutionary Basis of the Developmental Course and Etiologies of Anxiety and Disruptive Behaviors during Early Adolescence

STUDY_SECTION: CPDD

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


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: DAVIS

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Rates of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) in the United States have been rising exponentially over the past decade and the American Heart Association has identified the rigorous evaluation of naloxone’s efficacy in OA-OHCA as an important knowledge gap. There are currently no evidence-based methods for the real-time identification of OA-OHCA, making clinical trials of targeted naloxone in this population difficult. Developing externally valid and generalizable criteria to identify suspected OA-OHCA is the first step in designing an ethical and successful clinical trial of targeted-naloxone treatment in OA-OHCA, relevant to NIH’s mission to protect and improve health.

PI_NAMEs: DILLON, DAVID G (contact)

PROGRAM_OFFICER_NAME: REDMOND, NICOLE

PROJECT_TERMS: Accident and Emergency department;Address;adjudication;Age;Age Years;American Heart Association;antagonist;Autopsy;Blood;Canada;Cardiac;Characteristics;Clinical;Clinical Treatment;Clinical Trials;Clinical Trials Design;cohort;Coroner;County;Data;Data Set;Derivation procedure;design;Drug usage;Emergency Medicine;epidemiology study;Ethics;Etiology;Evaluation;Event;evidence base;experience;Funding;Future;Goals;Grant;Health;Heart Arrest;Hospitals;improved;inclusion criteria;innovation;instrument;Intervention;Investigation;Knowledge;Medical Examiners;Methods;Mission;Naloxone;National Heart, Lung, and Blood Institute;Opioid;opioid overdose;Opioid Receptor;opioid use disorder;out-of-hospital cardiac arrest;Patients;Pharmaceutical Preparations;Physicians;Population;Prevalence;Probability;prospective;randomized, clinical trials;Recommendation;Recording of previous events;Research;Residencies;Resuscitation;Retrospective cohort;Risk;Running;Safety;San Francisco;scale up;Scientist;screening;Secondary to;sudden cardiac death;Testing;Time;Toxicology;Training;United States;United States National Institutes of Health;Urine

PROJECT_TITLE: Improving the Identification of Opioid-Associated Out-of-Hospital Cardiac Arrest


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Obesity;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention

ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: PROJECT NARRATIVE This research will facilitate a holistic understanding of how early-life exposures and experiences shape chronic disease risk in children. The findings will provide insights into multi-level targets for preventive action, with a focus on preventing the development of obesity and related cardiometabolic traits in early life.

PI_NAMEs: BEKELMAN, TRACI ALLISON;DABELEA, DANA  (contact);PERNG, WEI

PROGRAM_OFFICER_NAME: ZANETTI, KRISTA A

PROJECT_TERMS: Address;Adolescence;Age;aged;Area;Asthma;Behavior;Behavioral;Biogenesis;Biological;Biology;Birth;Body Size;cardiometabolism;Caregivers;Chemicals;Child;Child Health;Childhood;Chronic;Chronic Disease;cohort;Collaborations;Collection;Colorado;Communities;COVID-19;Data;Deposition;Development;Developmental Disabilities;Diagnosis;Disease;disorder risk;Disparity;DNA Methylation;early childhood;Early identification;early life exposure;Environmental Exposure;Environmental Health;epidemiology study;Epigenetic Process;Ethnic Population;experience;Exposure to;Family;Fatty acid glycerol esters;Growth;Health;Health behavior;holistic approach;Household;in utero;Individual;infancy;innovation;insight;Institution;Joints;Knowledge;Lead;Life;Link;Mediating;Mental Depression;Metabolic;metabolomics;Methodology;middle childhood;Mothers;Neighborhoods;neurodevelopment;novel;Obesity;obesity development;obesity in children;offspring;Outcome;Overnutrition;Participant;Pathway interactions;Pattern;Pediatric cohort;pediatric health outcomes;Phenotype;Physiology;postnatal;Pregnancy;prenatal exposure;Prevalence;prevent;Preventive;programs;promote resilience;Protocols documentation;psychosocial;Psychosocial Stress;Publications;racial population;recruit;Research;Research Personnel;resilience;response;retention rate;Risk Factors;Sampling Studies;Science;Shapes;social;social stigma;Societies;Toddler;trait;Visceral;Weight;Work

PROJECT_TITLE: Environmental influences on Child Health Outcomes - The Colorado ECHO Pediatric Cohort

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-EPH-S(50)R]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Climate-Related Exposures and Conditions;Dementia;Lymphatic Research;Neurodegenerative;Neurosciences;Sleep Research;Social Determinants of Health;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: ROCHESTER

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Project Narrative A decline in brain fluid transport has been suggested to play a critical role in Alzheimer’s disease-related dementias. The proposed studies are based on the observation that short time exposure to inhaled ultrafine particles suppressed brain fluid transport. The proposed studies will identify the mechanistic link between air pollution and the increased risk of dementia.

PI_NAMEs: ELDER, ALISON ;GRAHAM, USCHI M;HUSSAIN, RASHAD  (contact)

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: abeta deposition;Acceleration;Address;Adrenergic Agents;Adverse effects;Affect;Age Months;aged;Aging;Air;Air Pollution;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease related dementia;Amyloid beta-Protein;Animal Model;APP-PS1;Astrocytes;Behavioral;bioprocess;Blood Vessels;Brain;brain health;brain parenchyma;brain tissue;Cells;Cerebrospinal Fluid;Cervical;Chemistry;Cognitive deficits;cognitive performance;comorbidity;Cranial Nerves;Dedications;dementia risk;Deposition;Development;Diameter;Disease;Disease Progression;Exhibits;experimental study;Exposure to;fluid flow;Functional disorder;Genetic;glymphatic clearance;glymphatic dysfunction;glymphatic function;glymphatic system;Human;Human Amyloid Precursor Protein;human model;Impaired cognition;improved;Inflammation;Inflammatory;Inhalation;Inhalation Exposure;innovation;Intercellular Fluid;interdisciplinary approach;Link;Liquid substance;lymphatic vessel;Maps;Meningeal;Modeling;Molecular;mouse model;Mus;mutant;Nervous System Disorder;Neurobiology;neuroinflammation;Organism;overexpression;Oxidative Stress;Particulate Matter;Pathologic;Pathology;Pathway interactions;Pattern;pharmacologic;Play;presenilin-1;Process;Proteins;regenerative;Resolution;response;Risk;Rodent;Rodent Model;Role;Scanning;Signal Transduction;Sleep;Sleep disturbances;sleep quality;Spinal nerve structure;Subarachnoid Space;System;systemic inflammatory response;Testing;Time;Tissues;Toxic Environmental Substances;Toxicology;Transgenic Organisms;Transmission Electron Microscopy;ultrafine particle;Venous;Waste Products;wasting;water channel;white matter;Wild Type Mouse

PROJECT_TITLE: Glymphatic impairment as a crucial factor in particulate matter exposure related development of Alzheimer's disease pathology

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AN-Z(55)R]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cardiovascular;Cerebrovascular;Dementia;Hypertension;Neurodegenerative;Neurosciences;Nutrition;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Hypertension is a leading risk factor for cognitive impairment and dementia, a condition affecting almost 50 million adults worldwide, and a major cause of death and disability. This application seeks to determine the mechanisms underlying the damaging effects of hypertension on the brain by focusing on salt-sensitivity and immune signaling, key features of human hypertension. By identifying the molecules and cells involved in the harmful effects of hypertension on the brain, our studies have the potential to provide novel therapeutic insights to protect the brain from the effects of high blood pressure.

PI_NAMEs: SANTISTEBAN, MONICA M (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Acetates;Adult;Affect;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;American Heart Association;Angiotensin II;Anti-Hypertensive Agents;Autopsy;base;Behavior;Blood Vessels;Brain;burden of illness;career;Cause of Death;Cells;cellular targeting;cerebral microvasculature;Cerebrospinal Fluid;Cerebrovascular Circulation;Cerebrovascular Disorders;cerebrovascular lesion;clinical diagnosis;Cognition;Cognitive;Consensus;cytokine;Data;Dementia;dementia risk;Deoxycorticosterone;Development;dietary salt;disability;DOCA;Endothelial Cells;Essential Hypertension;Excess Dietary Salt;Free Radicals;Functional disorder;genetic approach;Genetic Models;Goals;Health;Human;human model;Hypertension;hypertensive;IL17 gene;Immune;Immune response;Immune signaling;Impaired cognition;Impairment;Individual;Inflammatory;insight;knock-down;Knowledge;late life;Lead;Link;Macrophage;Mediating;Meningeal;Meninges;middle age;Modeling;mouse model;National Heart, Lung, and Blood Institute;National Institute of Neurological Disorders and Stroke;Neuroimmunomodulation;Neuronal Dysfunction;neurovascular;neurovascular unit;Nitric Oxide;novel strategies;novel therapeutic intervention;novel therapeutics;Nutrient;Oxidative Stress Induction;Pathology;Patients;Peripheral;pharmacologic;Predisposition;Prevention approach;Production;Public Health;Reactive Oxygen Species;receptor;Receptor, Angiotensin, Type 1;Regulation;Renin-Angiotensin System;Risk Factors;Rodent;Rodent Model;Role;salt intake;salt sensitive hypertension;Signal Pathway;Signal Transduction;Site;Sodium Chloride;Source;Stress;symposium;T cell infiltration;T-Lymphocyte;Testing;training opportunity;United States National Institutes of Health;Vascular blood supply;vascular cognitive impairment and dementia;vascular risk factor;working group

PROJECT_TITLE: Neuroimmune Mechanisms of Cognitive Impairment in Salt-sensitive Hypertension


ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Aging;Contraception/Reproduction;Genetics;Human Genome;Pediatric;Prevention;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative During meiosis, crossing-over between homologous chromosomes plays an essential role in preventing nondisjunction of homologs, with defects in segregation being the leading cause of miscarriages and chromosomal disorders. This project will illuminate features of the centromere effect, a meiotic crossover patterning phenomenon that excludes crossovers in centromere-proximal regions, and whose mechanism remains elusive to this day. Studying the centromere effect not only contributes towards understanding a phenomenon that safeguards against age-associated meiotic defects, but also fills a gap in knowledge regarding a fundamental cellular process.

PI_NAMEs: PAZHAYAM, NILA MADASSARY (contact)

PROGRAM_OFFICER_NAME: GUO, MAX

PROJECT_TERMS: Address;advanced maternal age;Affect;age related;Aneuploidy;Area;Attenuated;Biological Models;Cell Nucleus;Cell Physiology;Cells;Centromere;Chromosome Segregation;Chromosome Structures;Chromosomes;Congenital chromosomal disease;Consensus;Defect;design;Double Strand Break Repair;Down's Syndrome;Drosophila genus;Drosophila melanogaster;Ensure;Euchromatin;Event;Exclusion;Exhibits;experimental study;Female;fly;Frequencies;Genetic Crossing Over;Genetic Nondisjunction;Genetic Recombination;genome-wide;Global Change;Heterochromatin;Homologous Gene;homologous recombination;Incidence;Infertility;insight;Knowledge;Light;Mammals;Maternal Age;Measures;Meiosis;novel;older women;Oocytes;Organism;Participant;Pattern;Play;prevent;Process;Regulation;repaired;Research;Rest;Risk;Role;segregation;Spontaneous abortion;System;Testing;Work;X Chromosome;Y Chromosome

PROJECT_TITLE: Preventing Age-Associated Oocyte Aneuploidy: Mechanisms Behind the Drosophila melanogaster Centromere Effect

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-Q(20)L]


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE This project examines novel neoepitopes generated by the crinophagic pathway in pancreatic beta cells. We focus on a novel neoepitope family commonly identified in mice and humans with type 1 diabetes. The proposed studies will center on T cell pathogenicity, mechanisms of neoepitope generation, and translational implications of identified neoepitopes in human type 1 diabetes.

PI_NAMEs: WAN, XIAOXIAO  (contact)

PROGRAM_OFFICER_NAME: SECHI, SALVATORE

PROJECT_TERMS: Address;Affect;Alleles;Amino Acids;Animal Model;Animal Testing;Antigen Presentation;Antigens;Autoimmune;Autoimmune Diseases;autoimmune pathogenesis;Autoimmune Process;Autoimmune Responses;Autoimmunity;autoreactive T cell;autoreactivity;Beta Cell;Binding;Biological Assay;CD4 Positive T Lymphocytes;Cells;Cellular biology;Cellular Stress;Cysteine;Deterioration;Development;Diabetes Mellitus;diabetes pathogenesis;diabetic;diabetogenic;Elements;Endocrine;Epitopes;Family;Generations;Genetic;HLA-DQ8 antigen;Homeostasis;Human;immunogenic;Immunology;in vivo;Incidence;Inflammation;insight;Insulin;insulin dependent diabetes mellitus onset;insulin granule;Insulin-Dependent Diabetes Mellitus;islet;Islets of Langerhans;Knowledge;Laboratories;Link;Lysosomes;Modeling;Mus;Nature;neoantigens;novel;Outcome;Pathogenicity;Pathway interactions;Patients;Peptides;Peripheral Blood Mononuclear Cell;Persons;pharmacologic;Phenotype;Positioning Attribute;Post-Translational Protein Processing;Postdoctoral Fellow;Prevalence;Process;professor;programs;Reagent;repository;Research;Research Personnel;response;Risk;Role;secretory protein;Secretory Vesicles;Serine;Shapes;Siblings;Source;Structure of beta Cell of islet;System;T cell response;T-Lymphocyte;tenure track;Testing;Therapeutic;Tissues;Transgenic Model;translational applications;United States;Vesicle;Work

PROJECT_TITLE: The role of beta-cell crinophagy in generating diabetogenic neoepitopes

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


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

ORG_CITY: SAN DIEGO

ORG_NAME: SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE

PHR: Calorie restriction is beneficial in experimental models of Alzheimer’s disease. We propose experiments to determine to which extent these beneficial effects are due to the hypothermic response that occurs during calorie restriction.

PI_NAMEs: CONTI, BRUNO  (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Abbreviations;Affect;Age;age effect;age-related disease;Aging;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease model;Amyloid beta-Protein;Animal Model;Animals;anti aging;Attenuated;Back;Bacteria;Behavior;Behavioral;Biochemical;Biological;Body Temperature;Brain;Caenorhabditis elegans;Caloric Restriction;Calories;Cognitive;cognitive function;Cytoprotection;Data;Deterioration;Diet;dietary;dietary restriction;Disease;entorhinal cortex;Environment;Equilibrium;Evaluation;Evolution;Exhibits;Experimental Models;experimental study;Exploratory/Developmental Grant;extend lifespan;Female;Genetic;Glossary;Hamsters;Hippocampus;House mice;Housing;Human;human model;hyperphosphorylated tau;Hypothalamic structure;Impaired cognition;Incidence;Individual;Intake;Life Extension;life span;Longevity;male;Mammals;Measures;Mediating;Memory;Memory Loss;metabolome;mimetics;misfolded protein;Modeling;Molecular Chaperones;mouse model;Mus;Mutation;natural hypothermia;Nature;Neurodegenerative Disorders;neuroinflammation;neuropathology;neuroprotection;Organism;Outcome;overexpression;Pathology;Pathway interactions;phenomenological models;Plasma;Post-Translational Protein Processing;prevent;protein misfolding;Proteins;proteotoxicity;Regimen;response;Role;senescence;Senile Plaques;Stress;Swedish mutation;System;tau Proteins;Temperature;Testing;Tg2576;Therapeutic;Thermodynamics;Transgenic Model;transgenic model of alzheimer disease;virtual;Work;young adult

PROJECT_TITLE: Calorie Restriction, Body Temperature and Alzheimers Disease

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative It is imperative to identify new therapeutic targets in ccRCC, which is resistnt towares radio or chemotherapy. Here we provide evidence for the new oncogenic role of DCLK2 that regulates TBK1 activity and ccRCC tumorigenesis, which can be potentially therapetucially targeted. This study, if successful, will motivate the development of DCLK2 inhibitors in ccRCC and also provide a foundation for new therapeutic approaches for this lethal disease.

PI_NAMEs: ZHANG, QING  (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: ARNT gene;Cancer Cell Growth;cancer therapy;Cell Proliferation;Cells;chemotherapy;Clear cell renal cell carcinoma;Clinical;Complex;Data;Development;Disease;experimental study;factor A;Foundations;Genes;Growth Cones;HIF1A gene;Hypoxia Inducible Factor;Immune;Immune signaling;Impairment;In Vitro;in vivo;inhibitor;insight;Interferon Type I;IRF3 gene;Kidney;kidney cell;Malignant Epithelial Cell;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Molecular;Natural Immunity;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;novel therapeutic intervention;Oncogenic;Optic Nerve Injuries;overexpression;Pathway interactions;patient derived xenograft model;Patients;phosphoproteomics;Phosphorylation;Phosphotransferases;Play;Predisposition;preservation;Production;programs;Protein Dephosphorylation;Proteins;Publishing;Radiation therapy;Renal Carcinoma;Reporting;Resistance;Role;Signal Pathway;Signal Transduction;Small Interfering RNA;Specialized Program of Research Excellence;Specificity;Specimen;TANK-binding kinase 1;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;transcription factor;tumor;tumor growth;Tumor Promotion;Tumor Suppressor Proteins;tumor xenograft;tumorigenesis;ubiquitin-protein ligase;Ubiquitination;upstream kinase;VHL gene;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Identification of DCLK2-TBK1 signaling axis as a potential therapeutic target in kidney cancer

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Rare Diseases

PHR: Project Narrative: HHV-8-negative, idiopathic multicentric Castleman disease (iMCD) is a deadly hematologic illness with unknown cause and mechanisms. Our preliminary data suggest that uncontrolled PI3K/Akt/mTOR signaling is critical to iMCD pathogenesis, JAK1/2-mediated hypersensitivity to cytokine stimulation is a central mediator of iMCD pathogenesis, and JAK1/2 inhibition can mitigate iMCD in patients. Our proposed studies will advance understanding of iMCD pathogenesis, the mechanistic link between JAK1/2 and mTOR, and may lead to a new treatment paradigm for iMCD and related inflammatory and lymphoproliferative disorders.

PI_NAMEs: FAJGENBAUM, DAVID C (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Body System;Cell Physiology;cell type;Cells;Childhood;Circulation;Clinical;Critical Illness;cytokine;Cytokine Signaling;Cytotoxic Chemotherapy;Data;Data Discovery;Diagnosis;Disease;Disease Progression;Disease remission;Etiology;FDA approved;Flare;FRAP1 gene;Functional disorder;Funding;Goals;Hematology;Human;Human Herpesvirus 8;Hypersensitivity;Immune;improved;In complete remission;In Vitro;in vivo;Individual;Inflammatory;inflammatory marker;Interferon Type I;Interleukin-6;Interruption;IRS1 gene;JAK1 gene;JAK2 gene;Link;lymph nodes;Lymphoproliferative Disorders;Mediating;Mediator;monocyte;mTOR inhibition;Multicentric Angiofollicular Lymphoid Hyperplasia;new therapeutic target;novel;novel therapeutic intervention;Pathogenesis;Pathologic;Pathway interactions;patient subsets;Patients;Pharmaceutical Preparations;Phenotype;phenotypic biomarker;Phosphorylation;PI3K/AKT;PIK3CG gene;Proteomics;Rare Diseases;Refractory;Relapse;Research;Role;Sampling;Serum;Signal Pathway;Signal Transduction;Sirolimus;STAT3 gene;Symptoms;systemic inflammatory response;T-Cell Activation;T-Lymphocyte;Therapeutic Effect;treatment optimization

PROJECT_TITLE: JAK1/2 as a Central Regulator of iMCD Pathogenesis and Novel Therapeutic Target

STUDY_SECTION: CMIB

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


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF OPTOMETRY/OPHT TECH

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences;Pediatric

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF HOUSTON

PHR: PROJECT NARRATIVE Myopia, or nearsightedness, is a significant public health concern because, in addition to the high costs and the complications associated with traditional optical and surgical correction strategies, myopia can lead to permanent vision loss and ocular abnormalities causing blindness. Moreover, recent evidence suggests that the prevalence of myopia and, consequently, its impact are increasing rapidly. Hence, we aim to develop urgently needed treatment strategies to prevent and reduce the degree of myopia.

PI_NAMEs: OSTRIN, LISA A (contact)

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TERMS: Adolescent;Adrenergic Agonists;Adrenergic alpha-Agonists;Adult;Affect;Animal Model;Animals;Anisometropia;Biomechanics;Biometry;Birth;Blindness;Brimodine;Cavia;Cell Culture Techniques;Characteristics;Chick;Child;Childhood;Choroid;Clinical;Collagen;cost;Data;Development;Dinoprost;Dose;Economic Burden;effective therapy;Environment;Etiology;experience;experimental study;Exposure to;Extracellular Matrix;Eye;Fibrillar Collagen;Fibroblasts;Foundations;Goals;Growth;histological studies;Hour;Human;Hyperopia;In Vitro;in vivo;Incidence;Infant;Investigation;Knowledge;Latanoprost;Life;Light;light effects;Lighting;Macaca mulatta;Measurement;Mediating;Methods;Modeling;Monkeys;monocular;Myopia;novel;novel therapeutics;Ocular Pathology;Operative Surgical Procedures;Optics;Outcome Measure;Pathology;Pathway interactions;Pharmacologic Substance;Pharmacological Treatment;Physiologic Intraocular Pressure;Play;Population;Prevalence;prevent;primary outcome;Primates;Production;Productivity;programs;Proliferating;Property;protective effect;protein expression;Protocols documentation;Public Health;Quality of life;Refractive Errors;Research;Retina;Risk;Risk Reduction;Role;Sclera;socioeconomics;Synthetic Prostaglandins;targeted treatment;Techniques;Testing;Therapeutic Effect;therapy development;Time;Timolol;Translating;treatment strategy;Tupaiidae;Vision;Visual;Visual impairment

PROJECT_TITLE: Optically Induced Anisometropias

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


NIH_SPENDING_CATS: Biotechnology;Cystic Fibrosis;Genetics;Human Genome;Lung;Machine Learning and Artificial Intelligence;Rare Diseases

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Narrative: Given the current era of the highly effective modulator therapy (HEMT) Trikafta that has a pronounced, but incomplete, impact on the onset and progression of cystic fibrosis (CF), this proposal will address the interlinked roles of genetic and epigenetic diversity in CF to improve the Trikafta response from an environmental perspective. We will apply novel Gaussian process (GP) based machine learning computational approaches we have developed that can integrate genetic and epigenetic diversity observed across the CF population with experimental and clinical phenotypes. These studies will allow us to understand how histone deacetylase (HDAC), that manages cellular stress epigenetically through control of gene expression and protein function during development, aging and disease, can adjust the response to HEMT to improve the path to a cure in CF disease.

PI_NAMEs: BALCH, WILLIAM EDWARD (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Accounting;Acetylation;Affect;Aging;Automobile Driving;Bacterial Infections;Biology;Cell Death;Cell Physiology;Cells;Cellular Stress;Cessation of life;Chlorides;Chronic;Clinic;Clinical;clinical phenotype;Complex;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;Cytoprotection;Deacetylation;Delta F508 mutation;Development;Disease;Environment;Epigenetic Process;epigenetic profiling;epigenome;epigenomics;Equilibrium;Event;Fibrosis;Functional disorder;Funding;Gene Expression;Gene Proteins;Genetic;Genetic Diseases;Genetic Variation;genomic platform;Genomics;Genotype;HDAC7 histone deacetylase;Histone Acetylation;Histone Deacetylase;Histone Deacetylase Inhibitor;Hospitalization;Immune response;improved;Individual;Infection;Inflammation;Inflammatory Response;inhibitor;Intestines;Knowledge;Lead;Link;Logistics;loss of function;Lung;Lung Diseases;Machine Learning;Maps;Membrane;Mendelian disorder;misfolded protein;Mucociliary Clearance;novel;novel strategies;Organ;Outcome;Pancreas;Paper;Pathology;Pathway interactions;patient population;Patients;Performance;Personal Satisfaction;Phenotype;Play;Population;Population Heterogeneity;Post-Translational Protein Processing;prevent;Process;programs;protein folding;protein function;Protein Isoforms;Proteins;Proteomics;Publications;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Resolution;response;Role;Small Interfering RNA;Stress;Structure;Symptoms;synergism;Technology;Therapeutic;Time;Tissues;tool;trafficking;transcriptome;Treatment Efficacy;Variant

PROJECT_TITLE: Modulation of Lung Disease by Genetic/Epigenetic Profiling

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


FUNDING_MECHANISM: SBIR-STTR RPGS

ORG_CITY: Baltimore

ORG_NAME: SCANOGEN, INC.

ORG_STATE: MD

PHR: Project Narrative We propose the development of a highly multiplexed and automated molecular platform capable of detecting 90+ targets directly in whole blood in under 70 minutes with high sensitivity and specificity. If successful, the system will have broad applicability in biomedical applications. We will use the new platform to develop a diagnostic assay that responds to the urgent need for rapid identification of bloodstream pathogens in patients suspected of sepsis.

PI_NAMEs: CELEDON, ALFREDO ANDRES (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Antibiotics;antimicrobial;Architecture;Area;assay development;Biological Assay;Blood;Blood capillaries;Blood Circulation;Blood specimen;Clinical;Clinical Research;commercialization;Computer software;cost effective;cross reactivity;Cytolysis;Death Rate;design;Detection;detection assay;detection limit;detection method;Development;Device or Instrument Development;Diagnosis;diagnostic assay;Diagnostic tests;Engineering;Etiology;Future;Goals;Head;Hospitals;Image;instrument;Manuals;manufacturability;manufacture;Mass Spectrum Analysis;Methods;Microbe;microbial;Microbiology;microorganism;Molecular;multidisciplinary;multiplex assay;novel;novel strategies;operation;Optics;Organism;pathogen;Pathogen detection;Patients;Performance;Pilot Projects;Preparation;Price;Procedures;Process;Protocols documentation;prototype;Reagent;Resources;Risk;Sampling;Sensitivity and Specificity;Sepsis;single molecule;Specificity;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;standard of care;Symptoms;System;Technology;Testing;Time;Universities;usability;validation studies;Whole Blood;Work

PROJECT_TITLE: Highly Multiplexed Single Molecule Tethering


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease;Substance Misuse

ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE Alcohol abuse is a leading cause of morbidity and mortality worldwide and recent data indicate that alcohol- associated liver disease (ALD) affects over 10 million Americans. The overall objective of this proposal is to investigate how innate immune responses, in combination with alcohol-induced hepatocellular injury, coordinately lead to the pathogenesis of ALD. Understanding the complex interaction between alcohol-induced hepatocellular injury and inflammatory and fibrotic responses will provide the foundation for the future development of rationally designed therapeutic interventions to slow and/or reverse ALD.

PI_NAMEs: NAGY, LAURA E. (contact)

PROGRAM_OFFICER_NAME: PERRUCCIO, ELIZABETH M

PROJECT_TERMS: Acute;Adrenal Cortex Hormones;Affect;Alcohol abuse;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;American;Animal Model;Automobile Driving;Binding Proteins;Biogenesis;Biological Response Modifiers;C Type Lectin Receptors;Carbon Tetrachloride;CASP1 gene;Caspase;Cell Death;cell injury;Chronic;Cirrhosis;Clinical;Collagen;Complex;cytokine;Data;Deposition;Development;Disease;Disease Progression;Dose;effective therapy;end stage liver disease;Endotoxins;Ethanol;extracellular vesicles;Family;feeding;fibrogenesis;Fibrosis;Foundations;Future;Genes;Glucosylceramides;Hepatic;Hepatic Stellate Cell;Hepatitis;hepatocellular injury;Hepatocyte;hepatocyte injury;HMGB1 gene;IL18 gene;Impairment;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Injury;Innate Immune Response;Interleukin-1;Interleukin-1 beta;Interruption;Intervention;Intestinal permeability;IRAK3 gene;IRAK4 gene;Kupffer Cells;Lead;Ligands;Link;Lipid Binding;Lipopolysaccharides;Liver;Liver diseases;Liver Fibrosis;liver function;liver inflammation;liver injury;Macrophage;Malignant Neoplasms;Mediating;member;microbiota;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Nonlytic;novel;novel therapeutic intervention;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Peripheral Blood Mononuclear Cell;pharmacologic;Play;Primary carcinoma of the liver cells;Production;programs;Proteins;rational design;Reporting;response;Risk;Role;sensor;Serum;Serum amyloid A protein;Severity of illness;Signal Transduction;Spliceosomes;stellate cell;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;TLR4 gene;TNF gene;treatment strategy

PROJECT_TITLE: IRAKM and MINCLE in ALD

STUDY_SECTION: DBDT

STUDY_SECTION_NAME: Drug and Biologic Disposition and Toxicity Study Section[DBDT]


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

ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE Multiple sclerosis (MS) is an incurable immune-mediated demyelinating disease of the central nervous system that affects nearly 1 million Americans. Successful B cell depletion therapy in MS patients has invigorated intense interest in how pathogenic B cells contribute to disease. We will use our powerful novel B cell-dependent, antibody-independent EAE model to dissect mechanisms by which B cells shape the CD4 T cell response and determine the role of CNS B cells in autoimmune demyelinating disease.

PI_NAMEs: BOYDEN, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: Affect;American;Animal Model;Antibodies;Antibody Formation;Antigen Presentation;Antigen-Presenting Cells;Antigens;Autoimmune;Autopsy;autoreactivity;B cell therapy;B-Cell Activation;B-Cell Antigen Receptor;B-Lymphocytes;Blood;Bone Marrow;Brain;CD4 Positive T Lymphocytes;Cell Communication;Cell Shape;Cells;central nervous system demyelinating disorder;Central Nervous System Diseases;Cephalic;CXCR3 gene;cytokine;Data;Demyelinating Diseases;Demyelinations;Development;Disease;early onset;Economic Burden;Evaluation;Exhibits;Experimental Autoimmune Encephalomyelitis;Extracellular Domain;Flow Cytometry;Health;Helper-Inducer T-Lymphocyte;Histologic;Homing;Human;human model;IL17 gene;Immune;Immunization;Immunize;immunoreactivity;in vivo;Inflammation;insight;Integrin alpha Chains;Integrin alpha4beta1;interest;Interleukin-6;intravital imaging;Investigation;Kinetics;Lesion;Manuscripts;Mediating;Meningeal;Meninges;MHC Class II Genes;Modeling;Monoclonal Antibodies;mouse model;MS4A1 gene;Multiple Sclerosis;multiple sclerosis patient;Mus;Myelin;Myelin Proteolipid Protein;Nature;neuroinflammation;novel;Pathogenicity;Pathology;Pathway interactions;Patients;Peptides;Peripheral;Pharmaceutical Preparations;Phenotype;Play;polarized cell;Population;Positioning Attribute;Prevalence;Production;Proliferating;Research Personnel;response;Role;Shapes;Spinal Cord;success;Supporting Cell;Surface;Symptoms;T cell response;T-Cell Proliferation;T-Lymphocyte;Testing;Time;Tissues;transcription factor;transcriptome;United States;Visualization;Work

PROJECT_TITLE: Pathogenic B cell:CD4 T cell interactions in a novel B cell-dependent EAE mouse model of multiple sclerosis


NIH_SPENDING_CATS: Bioengineering;Genetics;HIV/AIDS

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative The proposed research is relevant to public health because it develops a deep and predictive molecular understanding of a process crucial for HIV-1 replication and may give rise to improvements in our ability to rationally interfere with this process for therapeutic intervention. Upon conclusion of the proposed studies, we will better understand the mechanisms that underlie RNA-protein interactions and the role of RNA structural dynamics in HIV-1 replication.

PI_NAMEs: AL-HASHIMI, HASHIM M (contact);GOFF, STEPHEN PAINE;HERSCHLAG, DANIEL

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Acceleration;Affinity;Arginine;Automobile Driving;Base Sequence;Behavior;Binding;Binding Proteins;Biochemical;Biochemistry;Biological Process;biophysical properties;Biophysics;Cell model;Cell Physiology;Cells;Communities;Complex;Computer Models;cost;Data;design;Development;Dissection;driving force;Elements;experimental study;Feedback;Future;Genetic Transcription;Genome;HIV-1;Human;improved;In Vitro;Libraries;Link;Maps;Measurement;Measures;Mediating;Methods;Modeling;Molecular;Molecular Computations;Molecular Conformation;molecular dynamics;prediction algorithm;predictive modeling;Process;Property;protein complex;Protein Conformation;protein data bank;Proteins;Public Health;Research;Resolution;Rest;RNA;RNA Conformation;RNA Databases;RNA Recognition Motif;RNA Sequences;RNA-Binding Proteins;RNA-Protein Interaction;Role;Science;small molecule;Structure;Technology;Testing;Therapeutic Intervention;Thermodynamics;three dimensional structure;Trans-Activators;Transactivation;Transcriptional Activation;Variant;Viral;Viral Proteins;viral RNA;Virus Replication;Work

PROJECT_TITLE: Development and application of a quantitive model for HIV-1 transcriptional activation driven by TAR RNA conformational dynamics


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Hematology;Infectious Diseases;Pediatric;Precision Medicine;Sepsis

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: PROJECT NARRATIVE Sepsis is a dysregulated host response to an infection and causes significant morbidity and mortality in children. Patients with sepsis are a mixed group, which present with heterogeneity of pathophysiology and different organ injury. The purpose of our proposal is to establish a biobank of patient small extracellular vesicles, which are pro-inflammatory microparticles released in serum and plasma by many cell types and which can be used as liquid biopsy for future research to determine the basis of sepsis heterogeneity and provide precision treatments.

PI_NAMEs: KAPLAN, JENNIFER MELISSA;ZINGARELLI, BASILIA  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Affect;beta-Lactams;biobank;Biochemical;Biogenesis;Biological;Biological Markers;biomarker identification;biophysical properties;Blood Cells;Blood specimen;Body Fluids;Categories;Cell Communication;cell type;Cells;Characteristics;Child;Childhood;Classification;Clinical;Clinical Trials;cohort;Collection;Complex;Critical Care;Critical Illness;Data;Data Set;Development;Diagnostics Research;Disease;Distant;effective therapy;Endosomes;Endothelial Cells;exosome;extracellular vesicles;Freezing;Functional disorder;Funding;Future;Genomics;Goals;Harvest;Health;Heart;Hepatocyte;Heterogeneity;high throughput analysis;Human;Immune;Immune response;improved;In Vitro;individual variation;Infection;Inflammatory;Inflammatory Response;Investigation;Kidney;lipidomics;Lipids;liquid biopsy;Liquid substance;Liver;Lung;Membrane;metabolomics;Methodology;MicroRNAs;Mind;Molecular;Molecular Profiling;Morbidity - disease rate;mortality;Multiple Organ Failure;nano-string;National Institute of General Medical Sciences;novel;Nucleic Acids;Organ;Organ failure;organ injury;Outcome;particle;patient subsets;Patients;Pediatric cohort;pediatric patients;pediatric sepsis;personalized medicine;pharmacometrics;Phase;Phased Innovation Awards;Phenotype;Phospholipids;Plasma;Population Heterogeneity;potential biomarker;Precision therapeutics;Procedures;Process;prospective;Proteins;Proteomics;Protocols documentation;Quality Control;repository;Reproducibility;Research;Research Personnel;RNA;RNA analysis;sample collection;Sampling;Sepsis;septic;septic patients;Septic Shock;Serum;Source;Specimen;Standardization;Syndrome;Therapeutic Research;Time;Tissues;tool;trait;transcriptome sequencing;transcriptomics;treatment strategy

PROJECT_TITLE: Biobank of small extracellular vesicles for pediatric sepsis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-ISB-D(02)M]


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases;Prevention

ORG_CITY: San Francisco

ORG_NAME: EXAVIR THERAPEUTICS INC.

ORG_STATE: CA

PHR: PROJECT NARRATIVE Despite the availability of successful HIV treatment regimens and prevention strategies, medicine-taking compliance is poor, and there remain nearly 40,000 new infections each year. To address this challenge, we have developed an injectable, nanoformulated antiviral prodrug that enables sustained HIV suppression and protection for up to one year. The work outlined in this Direct-to-Phase II SBIR application will complete the Chemistry, Manufacturing, and Controls, as well as IND-enabling studies, and prepare for a First-in-Human clinical trial.

PI_NAMEs: KEARNEY, BRIAN  (contact)

PROGRAM_OFFICER_NAME: DEY, BARNA

PROJECT_TERMS: Address;Adolescent;Adult;Adverse reactions;AIDS prevention;analytical method;Anti-Retroviral Agents;Biomedical Research;Canis familiaris;Carbon;Caring;CD4 Positive T Lymphocytes;Chemistry;Clinic Visits;Clinical Research;Clinical Trials;Data;Databases;Development;Documentation;Dose;drug development;drug production;drug resistance development;Effectiveness;emerging virus;Fatty Acids;FDA approved;Feedback;first-in-human;follow-up;Future;Guidelines;Health care facility;high risk;HIV;HIV Infections;HIV-1;HIV/AIDS;Human;improved;In Vitro;in vivo;Individual;Infection;infection rate;Injectable;Injections;Kilogram;Legal patent;Lymphoid;Macaca mulatta;Macrophage;manufacture;manufacturing scale-up;medication compliance;Medicine;men who have sex with men;Micronucleus Tests;monocyte;Mucous Membrane;Mutation;nano;nanoformulation;novel;Oral;oral HIV;pandemic disease;Patients;Persons;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Phase I Clinical Trials;Plasma;pre-exposure prophylaxis;pre-Investigational New Drug meeting;preference;Preparation;pressure;prevent;Prevention;Prevention strategy;Process;Prodrugs;Program Development;Proteins;Public Health;Quality of life;Rattus;Recommendation;Regimen;Research Institute;Risk;Rodent;Site;Small Business Innovation Research Grant;stability testing;Stearates;Sterilization;success;Surveys;Suspensions;systemic toxicity;Testing;Therapeutic;Toxicology;transgender women;Treatment Protocols;trial design;truvada;United States;United States Preventative Services Task Force;uptake;Viral;Viral Drug Resistance;viral transmission;Vulnerable Populations;Work

PROJECT_TITLE: XVIR-110 an ultra-long-acting INSTI for HIV pre-exposure prophylaxis in IND-enabling studies

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-F(12)]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Orphan Drug;Peripheral Neuropathy;Rare Diseases

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE KIF1A is the major generator of microtubule plus-end-directed motility in neurons and mutations in its motor domain cause devastating neurodevelopmental neurodegenerative diseases. We are studying the functional and structural mechanism by which KIF1A generates force and moves along microtubules and are determining the structural defects caused by disease mutations in KIF1A.

PI_NAMEs: GENNERICH, ARNE  (contact);SOSA, HERNANDO JOSE

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Affect;Amino Acids;Atrophic;autism spectrum disorder;autonomic neuropathy;Axon;Binding;Biological Assay;Brain Stem;Cell division;Cell Nucleus;Cell Physiology;cerebral atrophy;Complex;Cryoelectron Microscopy;Data;de novo mutation;Degenerative Disorder;Dense Core Vesicle;developmental disease;Disease;Docking;drug development;Dyes;Elements;Encephalopathies;Engineering;Etiology;Exhibits;falls;Family;Fluorescence;Fluorescence Resonance Energy Transfer;Frequencies;Functional disorder;Generations;Goals;Head;Human;human disease;improved;In Vitro;Individual;Inherited;innovation;insight;Intellectual functioning disability;Kinesin;Label;laser tweezer;Link;Measurement;Mediator;member;Microcephaly;Microtubules;migration;Modernization;Molecular;Molecular Motors;molecular targeted therapies;Motility;Motion;Motor;Mutagenesis;mutant;Mutation;N-terminal;Neck;Nervous System Disorder;Neurodegenerative Disorders;Neurodevelopmental Disorder;neuron development;Neurons;novel;nuclear power;Nucleotides;Optic Nerve;optic tweezer;Output;Pattern;Peripheral Nervous System Diseases;Phenotype;Physiological;Plus End of the Microtubule;Positioning Attribute;Presynaptic Terminals;Property;Protein Engineering;Proteins;Resolution;Series;Severities;single molecule;Spastic Paraplegia;stem cells;Structural defect;Structure;Synaptic Vesicles;System;Testing;Therapeutic;Therapeutic Intervention;Time;tool;unnatural amino acids;Work

PROJECT_TITLE: Structure and Mechanism of the Kinesin-3 Motor KIF1A

STUDY_SECTION: MSFC

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


NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Liver Disease;Nutrition

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Glycogen is the stored form of glucose and is present in the liver in large amounts. The metabolism of glycogen maybe affected by diseases such as diabetes, glycogen storage diseases and other liver conditions. In this project, we aim to develop a fast, non-invasive, three-dimensional magnetic resonance imaging technique to image the change of glycogen in the human liver.

PI_NAMEs: XU, XIANG  (contact)

PROGRAM_OFFICER_NAME: TSAP, LEONID V

PROJECT_TERMS: 3-Dimensional;Affect;Amides;bariatric surgery;Biological Assay;Blood Glucose;blood glucose regulation;Brain imaging;Breathing;Chemicals;Circulation;Clinical;clinical translation;Creatine;Deposition;Detection;Development;Diabetes Mellitus;Disease;Ensure;experimental study;Fasting;Fatty acid glycerol esters;Frequencies;Glucagon;Glucose;glucose metabolism;Glycogen;glycogen metabolism;Glycogen Storage Disease;glycogenolysis;Goals;Health;healthy volunteer;Hour;Human;Image;image reconstruction;imaging approach;Imaging Techniques;Imaging technology;improved;in vivo;Individual;Injections;Insulin;Intramuscular;Label;Lipids;Liver;liver biopsy;Liver Cirrhosis;Liver Glycogen;liver imaging;Magnetic Resonance Imaging;Measurement;Measures;Methods;Morphologic artifacts;Motion;Mus;NMR Spectroscopy;Nuclear;Nuclear Magnetic Resonance;nuclear Overhauser enhancement;Organ;Patients;Polymers;Preparation;prevent;Process;process optimization;Protocols documentation;Protons;Radial;reconstruction;Reporting;Scanning;Scheme;Signal Transduction;Spectrum Analysis;Speed;Spottings;stability testing;Structure;technique development;Techniques;temporal measurement;Testing;Time;Translations;Validation;Water

PROJECT_TITLE: Non-invasive Magnetic Resonance Imaging of Glycogen in the Human Liver

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative All living organisms encounter oxidative stress throughout their lifespan, and nature has evolved the oxidative stress response (OSR) to process noxious molecules such as reactive oxygen/nitrogen/carbonyl species (ROS/RNS/RCS). I propose to study obesity induced chronic dysregulated OSR by defining the role of posttranslational modifications (phospho-tyrosine) on the system of antioxidant enzymes. By elucidating the systemic changes in obesity-driven signaling and metabolism, we can better predict molecular targets for therapeutic intervention.

PI_NAMEs: TAMIR, TIGIST Y (contact)

PROGRAM_OFFICER_NAME: GIBBS, KENNETH D

PROJECT_TERMS: antioxidant enzyme;Antioxidants;Biochemical Reaction;biological adaptation to stress;Biological Assay;Cardiovascular Diseases;Cell Line;Cells;Chronic;Classification;Computer Models;Coupled;CRISPR interference;Data;Data Set;diet-induced obesity;dietary;dietary supplements;Disease;Drug Metabolic Detoxication;Enzyme Kinetics;Enzymes;Epidemic;Equilibrium;Evaluation;forest;Foundations;Future;Glutathione Metabolism Pathway;Glycine;Goals;High Fat Diet;high throughput screening;Homeostasis;human disease;In Vitro;in vitro Assay;in vivo;insight;interdisciplinary approach;Knowledge;life span;machine learning prediction;Malignant Neoplasms;Mentors;Metabolic;Metabolic syndrome;Metabolism;metabolomics;Modeling;Modification;molecular dynamics;molecular targeted therapies;mouse model;mutant;Nature;Nitrogen;Nonesterified Fatty Acids;Obesity;Organism;Oxidation-Reduction;oxidative damage;Oxidative Regulation;Oxidative Stress;Oxidative Stress Induction;Oxygen;Pathway interactions;Phase;Phenotype;Phosphorylation;Phosphotyrosine;Post-Translational Protein Processing;Primary carcinoma of the liver cells;Process;Production;Proteomics;Publishing;Recombinant Proteins;Regulation;Research;Research Personnel;Resolution;response;Risk Factors;Role;screening;Serine;sex;Signal Transduction;Site;small molecule;spatiotemporal;stoichiometry;Structure;supervised learning;Supplementation;System;Technical Expertise;Techniques;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Threonine;Training;training data;Tyrosine;Tyrosine Phosphorylation;unsupervised learning;Variant

PROJECT_TITLE: Regulation of oxidative stress signaling by tyrosine phosphorylation of antioxidant enzymes


NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Chronic Pain;Headaches;Migraine;Neurosciences;Pain Research

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: The trigeminal sensory innervation of the cranial meninges has been implicated in headaches and migraine. Yet, we do not clearly understand its sensory function and how it becomes activated in migraine. Our proposal will bridge this gap in knowledge by investigating the normal response of meningeal afferent neurons and the effects of agents implicated in migraine triggering in awake-behaving mice. Advances made could accelerate preclinical translational headache research.

PI_NAMEs: LEVY, DAN  (contact)

PROGRAM_OFFICER_NAME: OSHINSKY, MICHAEL L

PROJECT_TERMS: Acceleration;Afferent Neurons;allodynia;Anesthesia procedures;Automobile Driving;awake;Blood Vessels;Brain;cell type;Cephalic;Complex;Data;Development;Endowment;Exercise;Exhibits;Fiber;fluorescence imaging;Genetic;genetic approach;Head;Headache;Health;Homeostasis;Hour;Human;Image;imaging approach;Immunologics;innovation;Intracranial Hypertension;Intracranial Pressure;Ion Channel;Knock-out;Knowledge;Label;Link;Locomotion;Measurement;mechanical force;mechanical stimulus;Mechanics;Mediating;Meningeal;Meninges;Migraine;Molecular Genetics;Monitor;Mus;Nerve Endings;nerve supply;neural;Neurons;Nitric Oxide Synthase;Nitroglycerin;Nociception;novel;novel strategies;Operative Surgical Procedures;Pain;pain behavior;Pain Disorder;Pathologic;Physical activity;Physiological;Piezo 2 ion channel;Population;pre-clinical;Process;Property;Rattus;Research;response;Rest;Role;Sensory;sensory system;Signal Transduction;Sodium Channel;Stimulus;Stretching;Testing;Tissues;Transgenic Mice;Trigeminal System;two-photon;Vasodilation;vasomotion;voltage

PROJECT_TITLE: Response Properties of Meningeal Afferents in Health and Migraine

STUDY_SECTION: NPI

STUDY_SECTION_NAME: Neurobiology of Pain and Itch Study Section [NPI]