PHR: PROJECT NARRATIVE New understanding in the mechanism of therapy response and resistance is urgently needed to improve the treatment efficacy of metastatic prostate cancer, which is the second leading cause of cancer death in American men. Completion of this proposal provides new molecular insights in how prostate cancer cells use hypoxia and HIF1 to confer treatment resistance. It will lead to new prognosis and treatment strategies by providing candidates for biomarkers and therapeutic targets.

PI_NAMEs: QIAN, ZHENG DAVID  (contact)

PROGRAM_OFFICER_NAME: COVELL, DAVID G

PROJECT_TERMS: Alanine;Algorithms;alpha ketoglutarate;American;Anabolism;Androgen Antagonists;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Androgens;Automobile Driving;Biological;Biopsy Specimen;Bypass;cancer cell;Cancer Etiology;Cancer Patient;candidate marker;Cell model;Cells;Cessation of life;Chemicals;Clinical;clinical development;clinically significant;CRISPR/Cas technology;Cytoprotection;Data;deprivation;design;Development;Disease Outcome;Disseminated Malignant Neoplasm;drug efficacy;Energy Metabolism;enzalutamide;Enzymes;fatty acid biosynthesis;Fatty Acids;Genetic Transcription;Glucose;glucose metabolism;Glutamates;Glutamine;Growth;Human;Hypoxia;hypoxia inducible factor 1;Immunohistochemistry;improved;In Vitro;in vivo;inhibitor;insight;Link;lipid biosynthesis;Lipids;Literature;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;men;Messenger RNA;Metabolic;Metabolic Pathway;Metabolism;Metastatic Prostate Cancer;Modeling;Molecular;Monitor;mortality;Mus;neoplastic cell;novel;Oncogenic;Pathway interactions;patient derived xenograft model;Patients;Play;prevent;Prognosis;prostate cancer cell;prostate cancer cell line;prostate cancer progression;Protein Overexpression;Pyruvate;Resistance;resistance mechanism;response;Role;Sampling;screening;single cell analysis;Solid;standard of care;Testing;therapeutic target;therapy resistant;Tissue Sample;Transaminases;Transcriptional Regulation;transcriptome;transcriptomics;Treatment Efficacy;treatment response;treatment strategy;tumor;tumor hypoxia;tumor progression;Up-Regulation;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Adaptive resistance to AR inhibitors in hypoxia by GPT1

STUDY_SECTION: MCTB

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics B Study Section[MCTB]


ADMINISTERING_IC: HD

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Clinical Research;Genetic Testing;Genetics;Infant Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Rare Diseases;Tuberous Sclerosis

ORG_CITY: SEATTLE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: PROJECT NARRATIVE Newborn screening (NBS) is one of the most successful public health programs that provides cost-effective early diagnosis of treatable disorders while a major challenge for NBS of many treatable genetic disorders is the unavailability of a biomarker in dried blood spots (DBS). Given the facts that blood (in DBS) is a very complex mixture of proteins and that target proteins relevant to the diseases presented in this proposal are present at relatively low abundance, a technique called Immuno-SRM (Immunocapture coupled to selected-reaction- monitoring, or SRM) has been developed to quantify proteins in DBS. In this grant, our plan is to develop an Immuno-SRM method to quantify 19 peptides for NBS of 12 devastating but treatable genetic disorders using innovative method for covalent tagging of peptides so that several newborns can be analyzed simultaneously in one Immuno-SRM analysis and results easily decoded to link protein levels to each specific newborn.

PI_NAMEs: GELB, MICHAEL H;HAHN, SIHOUN  (contact)

PROGRAM_OFFICER_NAME: PARISI, MELISSA

PROJECT_TERMS: amino group;Bar Codes;Biochemical;Biochemical Genetics;Biological Assay;Biological Markers;Biological Process;Blood;C-terminal;Cell Therapy;Clinical;clinical development;Collection;commercialization;Complex Mixtures;cost effective;Coupled;Development;Disease;Dryness;Early Diagnosis;Early Intervention;effective therapy;Enzymes;Evaluation;experience;FDA approved;Funding;gene therapy;Genes;Genetic Diseases;genetic disorder diagnosis;Genetic Screening;Goals;Grant;Hepatolenticular Degeneration;high throughput screening;Individual;innovation;instrument;Laboratories;link protein;Lysine;Lysosomal Storage Diseases;Mainstreaming;Mass Spectrum Analysis;Measures;Methods;methyl group;Methylation;Modernization;molecular marker;Monitor;Monoclonal Antibodies;multiplex assay;Mutation;N-terminal;Nature;Neonatal;Neonatal Screening;Newborn Infant;next generation sequencing;novel;Patients;Peptides;Performance;Pilot Projects;Population;programs;protein function;Proteins;Proteomics;Public Health;Reaction;Running;Sampling;Scheme;screening;Screening procedure;small molecule;Spottings;System;Techniques;Testing;Time;TSC2 gene;Tuberous Sclerosis;tuberous sclerosis patients;Work

PROJECT_TITLE: Development of a Multiplex Proteomics Assay for High-Throughput Newborn Screening of a New Set of Treatable Neonatal Diseases

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Childhood Obesity;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative Emerging areas of research via the mechanistic human disease modeling approach have led to the development of new hypotheses and technologies to collect massive omics data (e.g. metabolites and epigenetic makers) that present great challenges to the mediation analysis. Mediation analysis is essential to understand mechanistic causal pathways of environmental perturbations and socioeconomic stressors on human health and health inequalities. The existing statistical methodologies are inadequate and underpowered to address major methodological challenges and translational research needs from such high-dimensional data analyses. Substantially motivated by analytic needs from several NIH-funded projects, the primary goal of this project is to advance novel methodological research on high-dimensional statistical inference, which will deliver a set of novel statistical models and efficient algorithms to support translational research in the connection to evaluating, interpreting, and predicting impacts of exposures to environmental and nutritional risk factors as well as socioeconomic determinants to human health, developmental outcomes and health disparity. These new toolboxes provide answers to the most benefit of disease prevention, health equality and health practice as well supporting evidence to new policies.

PI_NAMEs: PETERSON, KAREN EILEEN;SONG, PETER XUEKUN (contact)

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: Address;Adolescence;adolescent health outcomes;Adolescent obesity;Affect;Age;Algorithms;Area;Behavior;Biological Markers;Biological Process;Blood;Body Composition;Centers for Disease Control and Prevention (U.S.);Child;Child Health;Chronic;Chronic Disease;Clinical Pathways;Clinical Research;clinical translation;cognitive function;Complex;Computer software;Data;Data Analyses;Development;Diet;Dimensions;Disease;disease model;Disease Pathway;disorder prevention;DNA Methylation;economic determinant;Economics;Environmental Exposure;Epigenetic Process;Equation;experimental study;Exposure to;Foundations;Funding;Goals;Graph;Growth and Development function;Hand;Health;health disparity;health equality;health inequalities;health practice;high dimensionality;high throughput technology;Human;human disease;improved;innovation;interest;Intervention;Life;life span;Life Style;lipid biosynthesis;lipid metabolism;lipidome;Literature;Measurement;Mediation;Mediator;metabolomics;Methodological Studies;Methodology;Methods;methylation biomarker;Modeling;Molecular;molecular marker;multidimensional data;novel;Nutritional;Obesity;obesity development;online tutorial;operation;Outcome;outcome disparities;Parameter Estimation;Pathway interactions;Phenotype;Policies;Pregnancy;Prevention;Process;Research;Research Methodology;Risk Factors;Sample Size;Science;Scientist;Sexual Maturation;simulation;Site;social;Socioeconomic Status;socioeconomics;Statistical Methods;Statistical Models;Statistical Study;stressor;targeted biomarker;Technology;Testing;theories;Translational Research;United States National Institutes of Health;Update;user friendly software

PROJECT_TITLE: Statistical methods for analysis of high-dimensional mediation pathways

STUDY_SECTION: BMRD

STUDY_SECTION_NAME: Biostatistical Methods and Research Design Study Section[BMRD]


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Hematology;Liver Disease;Orphan Drug;Rare Diseases

ORG_CITY: PITTSBURGH

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE (Public health relevance statement) Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are two genetic diseases characterized by protoporphyrin IX (PPIX)-mediated phototoxicity and hepatotoxicity, and there is no cure. Targeting the transporter ABCG2, the current project will develop a novel strategy for the management of PPIX-mediated toxicities in EPP and XLP.

PI_NAMEs: MA, XIAOCHAO  (contact)

PROGRAM_OFFICER_NAME: DOO, EDWARD

PROJECT_TERMS: ABCG2 gene;analog;Attenuated;bile duct;Bile fluid;biliary tract;Binding Proteins;Bone Marrow;Chemicals;Cholestasis;Clinical;common symptom;cytotoxicity;Data;Drug Design;Drug Kinetics;Drug or chemical Tissue Distribution;Drug usage;efficacy evaluation;Enzymes;Erythrocytes;Erythropoietic Protoporphyria;Evaluation;Excretory function;ferrochelatase;Genetic Diseases;Genetic Engineering;Heme;heme biosynthesis;Hepatobiliary;Hepatocyte;Hepatotoxicity;hydrophilicity;Hydrophobicity;improved;in vivo;inhibitor;Life;Link;Liver;Liver Failure;liver injury;loss of function mutation;Malignant Neoplasms;Mediating;Metabolic;metabolic profile;Metabolism;mouse model;novel;novel strategies;novel therapeutics;Pathway interactions;Patients;Phototoxicity;Plasma;Play;prevent;Prevention;protoporphyrin IX;public health relevance;Pump;Role;Safety;Skin;Specificity;System;Testing;Therapeutic;Toxic effect;Toxic Environmental Substances;uptake;Work

PROJECT_TITLE: The ABCG2 transporter in protoporphyrin IX disposition: from toxicity to therapy

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular

ORG_CITY: TAMPA

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Vascular barrier breakdown is a hallmark of aberrant inflammation associated with trauma, infection, and cardiovascular diseases. There are currently no drugs that can effectively stop or prevent vascular leakage, owing to our incomplete understanding of its underlying mechanisms. We propose an in-depth investigation of the molecular and cellular reactions in the vascular wall during inflammation in hopes to identify new diagnostic or therapeutic targets for effective treatment of vascular inflammation.

PI_NAMEs: YUAN, SARAH Y (contact)

PROGRAM_OFFICER_NAME: GALIS, ZORINA S

PROJECT_TERMS: Address;animal data;Animal Model;Atherosclerosis;Biogenesis;Blood;Blood Vessels;Cardiovascular Diseases;Cells;clinically relevant;comparative;Cytoskeleton;Development;Diabetes Mellitus;drug development;effective therapy;Endothelial Cells;Endothelium;Event;Experimental Designs;extracellular;Extravasation;Functional disorder;Generations;Genetic;Glycocalyx;Histones;Human;human model;Imaging Techniques;In Vitro;in vivo;Infection;Inflammation;Inflammatory;inhibitor;Injury;innovation;insight;Intercellular Junctions;Investigation;Knowledge;leukocyte activation;Leukocytes;Mediating;Microcirculation;microvesicles;Molecular;Molecular Biology;molecular imaging;National Heart, Lung, and Blood Institute;neutrophil;new therapeutic target;novel;novel diagnostics;Organ;palmitoylation;Pathway interactions;Permeability;Pharmaceutical Preparations;pharmacologic;Post-Translational Protein Processing;prevent;Production;programs;Proteins;Reaction;receptor;Reporting;response;Role;Sepsis;Series;Signal Transduction;Sterility;Stroke;Structure;Surface;Techniques;Testing;theories;therapeutic target;Tissues;Translating;translational impact;Trauma;vascular inflammation;Vascular Permeabilities;Vesicle;Work

PROJECT_TITLE: Vascular Barrier Leakage in Inflammation


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: Chicago

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative The etiology of Alzheimer’s disease (AD) is unknown and satisfactory treatments for AD are unavailable. We hypothesize that microglial MyD88 signaling plays a predominant role in exacerbating AD-like pathophysiology in AD mouse models during aging and that chronic, systemic inflammation exacerbates AD-like pathophysiology via synergistic activation of MyD88 signaling in peripheral and brain immune cells in AD mouse models during aging. The long term goals of this study are to determine the roles of microglial and peripheral MyD88 signaling in the AD pathogenesis, to elucidate the molecular mechanism underlying the increased AD risk associated with systemic inflammation and to develop new preventive and therapeutic strategies for AD.

PI_NAMEs: FUKUCHI, KEN-ICHIRO  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: 3xTg-AD mouse;abeta accumulation;Acceleration;age related;Aging;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid beta-Protein;Animal Model;Bacterial Infections;Binding;Bone Marrow;Brain;brain parenchyma;CASP1 gene;Cell Death;Cells;Central Nervous System;Chronic;Cognition;cognitive function;cytokine;Cytoplasmic Protein;Data;Dementia;dementia risk;Deposition;Development;Disease;Disease Progression;Early Onset Familial Alzheimer's Disease;Etiology;Event;extracellular;Functional disorder;Genetic Risk;Genetic study;glial activation;Goals;hyperphosphorylated tau;IL18 gene;Immune;Immune response;In Vitro;in vivo;Inflammaging;Inflammasome;Inflammation;Inflammatory;Innate Immune Response;Interleukin Activation;Interleukin-1 beta;Late Onset Alzheimer Disease;marenostrin;Measures;Mediating;Microglia;mild cognitive impairment;Molecular;mouse model;Multiprotein Complexes;MYD88 deficiency;Nerve Degeneration;Neurofibrillary Tangles;neuroinflammation;neuron loss;Neurons;neuropathology;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;Peripheral;Play;Preventive;Preventive measure;Production;protein complex;Proteins;reconstitution;Risk;risk variant;Role;Senile Plaques;sensor;sex;Signal Pathway;Signal Transduction;Synapses;System;systemic inflammatory response;tau aggregation;tau Proteins;tau-1;Therapeutic;Virus Diseases

PROJECT_TITLE: Role of MyD88 signaling in systemic inflammation and Alzheimer disease


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Pediatric

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Over the past two decades, there has been an explosion in pediatric clinical studies requiring a deep understanding of pediatric clinical pharmacology. This has provided unprecedented opportunities in pediatric drug development and clinical pharmacology training. The proposed program will produce diverse pediatric clinical pharmacologists that will be well-trained to lead the efforts in pediatric drug development.

PI_NAMEs: BROUWER, KIM L.R.;GONZALEZ, DANIEL  (contact)

PROGRAM_OFFICER_NAME: SAMEDY BATES, LESLY

PROJECT_TERMS: Childhood;Clinical Pharmacology;post-doctoral training;Training Programs

PROJECT_TITLE: Duke-UNC Collaborative Pediatric Clinical Pharmacology Postdoctoral Training Program


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Genetics;Mental Health;Neurosciences;Women's Health Research

ORG_CITY: MINNEAPOLIS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative There are large sex differences in neurodevelopmental disorders, thought to result in part from sex differences in the effects of associated genotypes. Using touchscreen cognitive testing in mice, we will explore whether sex differences in the effect of a genetic variant seen in neurodevelopmental disorders on cognition are the result of male-specific changes in function in neural circuits involved in representing rewards and choices.

PI_NAMEs: GRISSOM, NICOLA  (contact)

PROGRAM_OFFICER_NAME: TONELLI, LEONARDO HERALDO

PROJECT_TERMS: 16p11.2;Animal Model;Animals;autism spectrum disorder;Behavior;Behavioral;biobehavior;Biology;Brain;Calcium Signaling;cell type;Cells;Choice Behavior;Cognition;Cognitive;cognitive testing;Complex;Computer Models;Copy Number Polymorphism;Corpus striatum structure;Data;Decision Making;Diagnosis;discounting;Dissociation;Dopamine;Equilibrium;Etiology;experimental study;Female;Fiber;flexibility;Fluorescence;frontal lobe;Functional disorder;Functional Magnetic Resonance Imaging;Gender;Genetic;genetic variant;genome-wide;Genotype;gray matter;Knowledge;Laboratories;Literature;Location;Magnetic Resonance;male;Measurement;Measures;Mediating;millisecond;Modeling;mouse model;Mus;neural circuit;neurodevelopment;Neurodevelopmental Disorder;Neurons;neuropsychiatric disorder;neuropsychiatry;Nucleus Accumbens;Outcome;Output;Pathway interactions;Pattern;Photometry;Positioning Attribute;Postdoctoral Fellow;Prognosis;Psychoses;Research;Rest;Rewards;Risk;Role;Scanning;sex;Sex Bias;Sex Differences;Signal Transduction;Task Performances;Testing;touchscreen;Variant;white matter;women versus men

PROJECT_TITLE: Sex-biased impacts of 16p11.2 variants on reward-guided choice

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Systemic lupus erythematosus (SLE) is an autoimmune disease with no known cure and limited effective therapies. A major comorbidity of SLE and common cause of death is accelerated atherosclerosis. This proposal seeks to determine whether defects in T cell metabolism underpin mechanisms for SLE autoimmunity and resulting cardiovascular disease and test two potential targets to address this unmet medical need.

PI_NAMEs: MAJOR, AMY S;RATHMELL, JEFFREY C. (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Acceleration;Acetyl Coenzyme A;Acetylation;Address;Affect;Affinity;alpha ketoglutarate;Anabolism;Animal Model;anti-cancer;Antigen-Antibody Complex;Arthritis;Atherosclerosis;ATP Citrate (pro-S)-Lyase;Autoantibodies;Autoimmune Diseases;Autoimmunity;autoreactive B cell;B-Lymphocytes;Bioenergetics;Bone Marrow;Cardiovascular Diseases;Cause of Death;CD4 Positive T Lymphocytes;Cells;Cellular Metabolic Process;Characteristics;Chimera organism;Chromatin;Chronic;chronic graft versus host disease;Citrates;Clinical Trials;comorbidity;conditional knockout;Consumption;Coronary Arteriosclerosis;cytokine;Data;Defect;Deposition;Disease;DNA;drug repurposing;effective therapy;Epigenetic Process;epigenetic regulation;Event;Frequencies;Gene Expression;Genetic;Glucose;Glucose Transporter;glucose uptake;Glutaminase;Glutamine;Helper-Inducer T-Lymphocyte;Histone Acetylation;histone methylation;Histones;Immune;Immunosuppression;Impairment;in vivo Model;Individual;Inflammation;Inflammatory;inhibitor;insight;Investigation;Knock-out;Mediating;Medical;Metabolic;Metabolic Pathway;Metabolism;Methylation;Modeling;Modification;mortality;mouse model;Mus;Nephritis;new therapeutic target;novel;pathogenic autoantibodies;Pathway interactions;Patients;Phase II Clinical Trials;Play;Production;programs;Proliferating;Publishing;Regulation;Regulatory T-Lymphocyte;response;Role;side effect;Signal Transduction;SLEB1 gene;Structure of germinal center of lymph node;Systemic Lupus Erythematosus;T cell differentiation;T-Cell Activation;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic;therapeutic target;transgene expression;tumor metabolism;vascular inflammation;Work

PROJECT_TITLE: Targeting Tfh Cell Metabolic Regulation in SLE and SLE-Associated Atherosclerosis

STUDY_SECTION: HAI

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


NIH_SPENDING_CATS: Autism;Brain Disorders;Clinical Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: NARRATIVE Unlike de novo gene mutations, which cannot be avoided, chemical exposures can be minimized or eliminated, particularly during critical periods of brain development. Our research will evaluate thousands of chemicals, including mixtures, and identify those with the greatest potential to impact neurodevelopmental processes. This new knowledge will enable us and others to evaluate real-world risks associated with these chemicals/mixtures, permit future generations to minimize exposure, and help to reduce the prevalence of avoidable neurodevelopmental disorders—those that are caused or exacerbated by chemical risks.

PI_NAMEs: ZYLKA, MARK J. (contact)

PROGRAM_OFFICER_NAME: LAWLER, CINDY P

PROJECT_TERMS: Affect;Attention;Attention deficit hyperactivity disorder;autism spectrum disorder;behavioral phenotyping;Biological Monitoring;Brain;building materials;Chemical Exposure;Chemicals;CRISPR/Cas technology;critical period;Data;Development;Developmental Delay Disorders;Disease;End Point Assay;Engineering;Environment;Environmental Health;Environmental Risk Factor;Exposure to;fungicide;Future Generations;Gene Mutation;Genetic;Goals;Heritability;high throughput screening;Home environment;Human;human model;Impairment;in vivo;Individual;Joints;Knowledge;life span;Link;Maternal Exposure;Mitochondria;Molecular Target;mouse model;mucidin;Mutation;nerve stem cell;Neurodevelopmental Disorder;Neurons;Pathology;Pathway interactions;Persons;Pesticides;Placenta;Plastics;Predisposition;Pregnancy;prenatal exposure;Prevalence;Process;programs;Public Health;pyrethroid;Research;Research Personnel;Risk;Sampling;Time;Valproic Acid;Work

PROJECT_TITLE: Environmental-use chemicals that target pathways linked to autism and other neurodevelopmental disorders


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE While ADHD typically onsets in early childhood, there are lengthy delays in the identification of the disorder frequently spanning many years putting the children at risks for developing adverse consequences. This calls for improved efforts in early identification of young children at risk for ADHD. In the K23 award, I aim to identify clinical indicators and neural biomarkers of the risk for ADHD that will foretell which preschool aged, pre- syndromatic children will develop ADHD by their early elementary school years.

PI_NAMEs: UCHIDA, MAI  (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: Accidents;Address;Adolescent;Adult;adverse outcome;Affect;Age;Anxiety;Anxiety Disorders;Area;Attention;Attention deficit hyperactivity disorder;Award;Behavior;Behavioral;Biological Markers;Biometry;Board Certification;Brain;career;Cerebrum;Characteristics;Child;Child Behavior Checklist;Childhood;Clinical;clinical biomarkers;Clinical Data;clinical diagnosis;clinical predictors;Data;Data Collection;Development;Diagnosis;Diagnostic;Dimensions;Disease;Dyslexia;early childhood;Early identification;early onset;Education;elementary school;Executive Dysfunction;executive function;Failure;Family Study;Future;Goals;Heritability;high risk;Impairment;improved;Injury;Intervention;Laboratories;Leadership;Link;longitudinal design;Measurement;Measures;Mental Depression;Mental disorders;Mentored Patient-Oriented Research Career Development Award;Mentorship;Monitor;Mood Disorders;Moods;National Institute of Mental Health;neural;neural circuit;Neurobiology;Neurodevelopmental Disorder;neuroimaging;neuroimaging marker;Nursery Schools;offspring;Outcome;Parents;Population;Population Heterogeneity;Positioning Attribute;predictive marker;preventive intervention;prospective;psychiatric comorbidity;Psychiatrist;Psychopathology;Research Personnel;Risk;Sampling;School-Age Population;Short-Term Memory;Statistical Data Interpretation;Strategic Planning;Substance Use Disorder;Syndrome;Training

PROJECT_TITLE: Neural and Clinical Biomarkers of Risk for ADHD:  A Focus on Preschoolers

STUDY_SECTION: CPDD

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


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Hypertension;Nutrition;Prevention

ORG_CITY: BALTIMORE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Narrative It is unknown if the DASH eating pattern, a diet rich in fruits and vegetables, can improve glucose control and reduce glycemic variability in adults with type 2 diabetes. We will address this gap in the literature using a randomized clinical trial design. The results of this study will inform dietary recommendations in patients with diabetes.

PI_NAMEs: SELVIN, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: GOROSPE, RAFAEL

PROJECT_TERMS: Address;Adult;Affect;American;Ancillary Study;Biological Markers;Blood Glucose;blood glucose regulation;Blood Pressure;blood pressure elevation;Clinical;Clinical Trials Design;cohort;Continuous Glucose Monitor;COVID-19 pandemic;DASH diet;Data;design;Diabetes Mellitus;Diet;dietary;Dietary Factors;Dietary Sodium;Eating;feeding;Frequencies;Fructosamine;fruits and vegetables;Funding;Future;Glucose;glycemic control;Glycosylated hemoglobin A;glycosylated serum albumin;Goals;Grant;Hyperglycemia;Hypoglycemia;improved;Insulin-Dependent Diabetes Mellitus;Intake;Intervention Trial;Laboratories;Level of Evidence;Literature;Measures;Non-Insulin-Dependent Diabetes Mellitus;Participant;Patients;Pattern;Persons;Population;primary endpoint;randomized, clinical trials;Recommendation;Research Personnel;Risk;Running;secondary endpoint;Site;Sodium;Testing;Time;Universities;Variant

PROJECT_TITLE: Effects of the DASH diet on glucose patterns in adults with type 2 diabetes

STUDY_SECTION: CIDO

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Disability Research;Dissemination and Implementation Research;Health Services;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Prevention

ORG_CITY: EAST LANSING

ORG_DEPT: PSYCHOLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: Project Narrative Despite strong consensus that early, specialized intervention for children with Autism Spectrum Disorder (ASD) can have a dramatic impact on outcomes, the public health system’s capacity to provide such services is severely challenged by the rapid rise in ASD prevalence. The goal of this research is to increase timely and equitable access to ASD-specialized early intervention during the critical first three years of life by capitalizing on the existing infrastructure of the Part C Early Intervention (EI) system, which is publicly funded and available in all U.S. States. This project will train EI providers to use an evidence-based, inexpensive, parent-mediated intervention that can improve child and family outcomes as well as mitigate the substantial economic costs associated with ASD.

PI_NAMEs: INGERSOLL, BROOKE  (contact)

PROGRAM_OFFICER_NAME: PUGLIESE, CARA ELISABETH

PROJECT_TERMS: acceptability and feasibility;Address;Aftercare;Age;Area;autism spectrum disorder;autism symptoms;autistic children;Behavior;Behavior Therapy;Birth;Characteristics;Child;Child Language;Child Rearing;clinically relevant;Code;Consensus;Consensus Development;Consultations;Data;data management;Development;Developmental Delay Disorders;Developmental Disabilities;dosage;Early Intervention;economic cost;Educational process of instructing;Effectiveness;effectiveness evaluation;effectiveness testing;effectiveness/implementation design;effectiveness/implementation hybrid;Equity;evidence base;Evidence based intervention;Family;Family member;follow-up;Funding;Future;Goals;Health system;Heterogeneity;Home;hybrid type 1 design;Hybrids;implementation determinants;implementation evaluation;improved;improved outcome;Individuals with Disabilities Education Act;Infrastructure;innovation;Intervention;intervention program;Interview;joint attention;Language;Language Development;language outcome;Lead;Learning;Life;Measures;Mediating;member;Methods;Modification;Motor;multi-site trial;National Institute of Mental Health;Outcome;Parents;Patient Self-Report;Personal Satisfaction;Play;Population;Prevalence;Procedures;Protocols documentation;Provider;provider intervention;Public Health;quality assurance;Quality of life;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Reporting;Research;Role;Sample Size;Sampling;Self Efficacy;service delivery;service intervention;Services;Site;social communication;Source;Stress;System;Technology Assessment;Testing;Training;treatment as usual;treatment effect;Variant

PROJECT_TITLE: 2/4: Improving the Part C Early Intervention Service Delivery System for Children with ASD: A Randomized Clinical Trial


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: SAINT LOUIS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative DNA helicases, translocases and single stranded DNA binding (SSB) proteins play fundamental roles in DNA metabolism in all organisms including humans. Mutations in a number of human DNA helicases are linked to several human diseases. Because of their pivotal roles in nucleic acid metabolism in all organisms, including bacteria, helicases are prime targets for drugs or antibiotics that may inhibit them specifically. Our basic studies of SSB and its interacting proteins in bacteria can potentially lead to new targets for the development of novel antibiotics.

PI_NAMEs: LOHMAN, TIMOTHY M (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Address;Affect;Allosteric Regulation;Antibiotics;Armadillo Repeat;Bacteria;Binding;Binding Proteins;C-terminal;Communication;Complex;Defect;Development;Disease;DNA;DNA Binding;DNA biosynthesis;DNA Double Strand Break;DNA metabolism;DNA Repair;DNA Repair Pathway;DNA-Binding Proteins;Drug Targeting;Escherichia coli;Fluorescence;Genetic Recombination;Genome;helicase;Human;human disease;human DNA;Kinetics;laser tweezer;Link;Maintenance;melting;Molecular Motors;Motor;Mutation;novel;nuclease;nucleic acid metabolism;optic tweezer;Organism;Play;Process;Property;Proteins;repaired;Role;single molecule;Single-Stranded DNA;Site;SS DNA BP;Tail;Thermodynamics;translocase;Variant

PROJECT_TITLE: Mechanisms of Helicases, Translocases and SSB Proteins involved in Genome Maintenance

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


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Eczema / Atopic Dermatitis

ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Narrative: Mast cells play important roles in anaphylaxis, asthma, atopic dermatitis and other chronic inflammatory diseases. We have discovered novel pathways via which functions of mast cells are regulated. Understanding the molecular mechanisms involved in this regulation may provide new approaches for the modulation of mast cell-mediated allergic and inflammatory diseases.

PI_NAMEs: ALI, HYDAR  (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Actins;Adaptor Signaling Protein;ADRBK1 gene;airway hyperresponsiveness;Allergic Contact Dermatitis;Allergic Disease;allergic response;Anaphylaxis;Antigens;Arr2;Asthma;Atopic Dermatitis;Attenuated;B-Cell Lymphomas;beta-arrestin;Cell Aggregation;Cell Degranulation;Cell surface;Cells;Cellular biology;chemokine;Chemotaxis;chronic inflammatory disease;cofilin;Connective Tissue;CRISPR/Cas technology;Cutaneous;cytokine;depolymerization;desensitization;Development;Disease;Environment;G protein coupled receptor kinase;G-Protein-Coupled Receptors;Generations;Hematopoietic;Histamine;Homeostasis;Host Defense;Hypersensitivity;IgE;IgE Receptors;Immune;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Response;Life;mast cell;Mediating;Membrane Proteins;Modeling;Molecular;Mucosa- associated lymphoid tissue lymphoma translocation protein-1;Mucous Membrane;Mus;mutant;Neurogenic Inflammation;novel;novel strategies;novel therapeutics;Pain;Passive Cutaneous Anaphylaxis;Pathway interactions;Peritoneal;Phosphorylation;Play;polymerization;Polymers;PRKCA gene;Production;protein activation;Protein Dephosphorylation;protein kinase C beta;Proto-Oncogene Proteins c-akt;Pruritus;Pulmonary Inflammation;receptor;recruit;Regulation;Resistance;response;Role;Scaffolding Protein;Signal Pathway;Signal Transduction;Skin Tissue;Testing;Tissues;Tryptase

PROJECT_TITLE: Novel Roles of GRK2 and beta-arrestin2  on mast cell-mediated allergy and Inflammation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)]


ORG_CITY: DENTON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF NORTH TEXAS

ORG_STATE: TX

PHR: Project Narrative    Our  mission  is  to  provide  a  biomedical  Ph.D.  training  program  that  is  truly  inclusive,  culturally  responsive,  increases  diversity,  enhances  student  scientific  skill  sets,  develops  student  career  and professional skill sets, provides new opportunities for the participants, and increases faculty  development  as  a  mentor.  The  primary  goal  of  the  UNT  G- RISE  program  is  to  increase  the  number of trainees from underrepresented groups who enter and complete a Ph.D. and enter into  the  biomedical  and  behavior  science  workforce.    To  align  with  this  goal,  the  objectives  of  this  training  program  are  to  1)  further  develop  an  inclusive,  diverse,  and  culturally  responsive  predoctoral  training  program;;  2)  provide  high- quality  scientific  training  for  Ph.D.  students  in  the  Biomedical Sciences;; 3) provide student participants with career and professional training;; and 4)  enhance the Ph.D. mentoring experience for both students and mentors.

PI_NAMEs: BURGGREN, WARREN ;HUGHES, LEE ;PADILLA, PAMELA ANNE (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Texas;Universities

PROJECT_TITLE: G-RISE at the University of North Texas

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Organ Transplantation;Regenerative Medicine;Transplantation

ORG_CITY: TALLAHASSEE

ORG_NAME: FLORIDA AGRICULTURAL AND MECHANICAL UNIV

PHR: Liver diseases afflict millions of individuals in the United States, yet there are no effective treatments to curb the pathology and there remains a shortage of available livers for transplantation. However, a viable solution is the use of a model liver system that accurately mimics the biomechanical and biochemical functioning of in vivo liver tissue. This will be achieved through the development of a novel 3D printed bioscaffold for assembly of a liver organoid for in vivo tissue restoration and ex vivo drug screening.

PI_NAMEs: ALI, JAMEL  (contact)

PROGRAM_OFFICER_NAME: FRINCU, CRINA

PROJECT_TERMS: 3-Dimensional;3D Print;Adoptive Transfer;aging population;Animal Experiments;Animal Model;Autologous;Biochemical;Biocompatible Materials;Biological Models;Biomechanics;Biomedical Engineering;bioprinting;bioscaffold;Cells;Cessation of life;copolymer;design;Development;diagnostic screening;Dialysis procedure;Disease;Drug Compounding;drug discovery;Drug Screening;Drug Targeting;effective therapy;Engineering;Evaluation;Future;Graft Rejection;Health;Hepatic;Hepatic Tissue;Hepatocyte;Hepatotoxicity;high throughput screening;Human;Immune response;Implant;implantation;In Vitro;in vitro Model;in vivo;in vivo engraftment;in vivo Model;in-vitro diagnostics;indexing;Individual;innovation;Investigation;Laboratories;Legal patent;Liver;Liver diseases;Liver Failure;liver function;liver injury;liver transplantation;Measures;Metabolic;Methods;mimetics;Modeling;Monitor;mouse model;Mus;novel;Organoids;Pathology;Persons;Physiological;Printing;Property;Publishing;rapid technique;Reporting;response;restoration;scaffold;screening;spheroids;Structure;success;System;Therapeutic;three dimensional cell culture;Tissue Donors;tissue support frame;Tissues;tool;Toxic effect;Transplantation;United States;viscoelasticity;Work

PROJECT_TITLE: Engineering a Novel Bio-Scaffold for Hepatic Tissue Restoration and Drug Screening


NIH_SPENDING_CATS: Biotechnology

PHR: Project Narrative Phototherapeutics offer the promise of targeted delivery at diseased sites with a consequent reduction in untoward side effects. We’ve developed an erythrocyte-based carrier system that conveys phototherapeutics throughout the circulatory system. The proposed research program seeks to assess the (a) the mechanism of drug release, (b) optimized structural motifs for efficient drug delivery, (c) drug scope, (d) therapeutic efficacy, and (e) optimized photo-delivery parameters.

PI_NAMEs: LAWRENCE, DAVID S. (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: absorption;Address;Adverse effects;aggressive therapy;analog;Attention;Behavior;Biochemistry;Biological;Cardiovascular system;Cell surface;Cells;Circulation;Clinical Trials;Combined Modality Therapy;design;Disease;dosage;drug action;Drug Delivery Systems;drug disposition;Drug Kinetics;Elements;Enzymatic Biochemistry;Erythrocytes;Eye;Face;fluorophore;functional group;Generations;Half-Life;improved;in vivo;inhibitor;interest;Light;Malignant Neoplasms;Mediating;Metabolic;Metabolism;Modification;Molecular;new technology;Optics;Organism;Parents;Penetrance;Penetration;peptide drug;Peptides;Pharmaceutical Preparations;photolysis;Phototherapy;Plasma;Positioning Attribute;Prodrugs;programs;Property;Proteins;Reactive Oxygen Species;Reporting;Research;scaffold;side effect;Site;small molecule;small molecule therapeutics;standard of care;Surface;System;targeted delivery;targeted treatment;Technology;Therapeutic;Therapeutic Agents;therapeutic protein;Tissues;Toxic effect;Treatment Efficacy;Vitamin B 12;water solubility

PROJECT_TITLE: Design and Application of Photoresponsive Modules in Circulating Erythrocytes

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Liver Disease;Nutrition;Obesity

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease, with prevalence growing in parallel with the obesity epidemic. NAFLD has no approved pharmacotherapy, due to incomplete understanding of its molecular mediators which is compounded by its unpredictable progression to liver fibrosis, the major determinant of morbidity/mortality of this disease. In this application, we study the potential role of hepatocyte-derived Adipsin, previously considered an adipose-specific secreted factor, to induce liver fibrosis.

PI_NAMEs: PAJVANI, UTPAL  (contact)

PROJECT_TERMS: Adipocytes;Adipose tissue;Alternative Complement Pathway;Animals;Binding;C3AR1 gene;Cells;chronic liver disease;Coculture Techniques;comorbidity;Complement;Complement 3a;Complement 3b;Complement Activation;Complement Factor D;Complication;Conditioned Culture Media;CRISPR/Cas technology;Cross-Sectional Studies;cytokine;Data;Data Set;Development;Diet;dietary;Disease;disease heterogeneity;Disease Progression;experimental study;feeding;Fibrosis;Genetic Transcription;Goals;Hepatic Stellate Cell;Hepatocyte;Human;In Vitro;in vitro activity;in vivo;inhibitor;knock-down;Knock-in Mouse;Knock-out;knockout animal;Knockout Mice;Lipids;Liver;liver biopsy;Liver Fibrosis;liver inflammation;liver transplantation;LoxP-flanked allele;Mediating;Mediator;Metabolic;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;obese patients;Obesity;Obesity Epidemic;overexpression;pandemic disease;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Pharmacotherapy;Phenocopy;Phenotype;Play;Population;PPAR gamma;PPARgamma2;Prevalence;Prevention strategy;Protein Isoforms;Protein Secretion;Proteolysis;receptor;Recombinants;Reproducibility;Role;Signal Transduction;small hairpin RNA;Small Interfering RNA;Testing;Therapeutic;tool;transcriptome sequencing;transcriptomics;translational potential;treatment strategy;Viral Vector;Wild Type Mouse

PROJECT_TITLE: Adipsin in NASH

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


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

PHR: Proposed research is designed to determine the molecular mechanisms by which arsenic exposure alters the homeostatic function of neural cellular populations (neurons, astrocytes, and microglia) during different developmental stages and with aging. Furthermore, we will determine alterations in synaptic pruning and LXR regulated lipid homeostasis. These mechanism could trigger impaired neuronal development and biogenesis, dysregulated synaptic plasticity and chronic neuroinflammation, impacting over all cognition and predisposing the brain to neurodegeneration later in life.

PI_NAMEs: FITZ, NICHOLAS FRANCIS (contact)

PROJECT_TERMS: Acceleration;Acetylation;ADD-1 protein;Adult;Affect;Age;Aging;aging brain;aging related;Alzheimer associated neurodegeneration;Alzheimer's Disease;Alzheimer's disease risk;Arsenic;Astrocytes;ATP binding cassette transporter 1;Biochemical;Bioenergetics;Biogenesis;Blood;Blood - brain barrier anatomy;Brain;brain cell;Brain Injuries;Brain Pathology;cancer cell;cardiovascular disorder risk;Cell Communication;cell injury;cell type;Cells;Central Nervous System;Child;Cholesterol;Chronic;Clinical;Cognition;Cognitive deficits;Complement;Complex;Cytoskeletal Proteins;Data;Dementia;design;Development;Disease;disorder risk;DNA Methylation;Embryonic Development;Environment;Environmental Exposure;Environmental Risk Factor;epidemiology study;epigenetic marker;Epigenetic Process;epigenetic regulation;epigenome;epigenomics;Etiology;Exposure to;fatty acid metabolism;Fatty Acids;Functional disorder;gene environment interaction;Gene Expression;Generations;Genes;Genetic;genetic signature;Genetic Transcription;genome wide association study;Health;Heavy Metals;histone modification;Histones;Homeostasis;Human;Image;immune function;Immune system;Impaired cognition;Impairment;improved;in utero;Inflammation;Inflammatory;Inflammatory Response;Injury;injury and repair;Life;lifestyle factors;Lipid Peroxidation;lipid transport;Lipids;Liver X Receptor;Lysine;Malignant Neoplasms;Mediating;Membrane;Metabolic;Metabolic Diseases;Metabolic Pathway;Metabolism;Methylation;Microglia;Mitochondria;mitochondrial dysfunction;Modification;Molecular;Nerve Degeneration;nerve injury;neural;Neurodegenerative Disorders;neurodevelopment;Neuroglia;neuroinflammation;neuron development;Neurons;Neurophysiology - biologic function;neuroprotection;Nuclear Receptors;Organ;Outcome;Oxidative Stress;Oxygen Consumption;Pathogenesis;Pathologic;Pathology;Pathway interactions;Peripheral;peroxidation;Persons;Placenta;Play;Poison;Population;postnatal;Predisposition;prenatal;Process;Reactive Oxygen Species;receptor expression;Receptor Signaling;Research;response;response to injury;risk variant;Role;RXR;Signal Transduction;single-cell RNA sequencing;Stimulus;Stress;Synapses;Synaptic plasticity;synaptic pruning;Synaptosomes;Tail;Testing;Toxic Environmental Substances;Toxicant exposure;Transcription Alteration;transcriptomics;two-photon;Untranslated RNA;Water

PROJECT_TITLE: Neurodevelopmental and neurodegenerative effects of environmental determinants: altering neural cellular populations impacting homeostatic functions and inflammatory response.

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Congenital Structural Anomalies;Genetics;Heart Disease;Human Genome;Pediatric

PHR: Project Narrative A continuing mystery in human biology is how the same genetic material can give to the more that 200 different types of cells found in the body. My proposal is focused on understanding how the genetic material in cardiac cells is organized in three-dimensions and revealing how that organization is maintained throughout the lifetime of a cell. These studies will help identify new therapeutic strategies for patients with disease that result from the failure to properly establish or maintain the correct organization in cardiac cells.

PI_NAMEs: JAIN, RAJAN  (contact)

PROGRAM_OFFICER_NAME: SCHRAMM, CHARLENE A

PROJECT_TERMS: 3-Dimensional;Architecture;Cardiac;cardiogenesis;cell type;Cells;Chromatin;congenital heart abnormality;Development;Disease;Engineering;Epigenetic Process;epigenome;Equilibrium;Failure;flexibility;Gene Expression;Genes;genetic manipulation;Genetic Materials;Genetic Transcription;Genome;Genomics;Heart Diseases;Heart failure;Human;Human Biology;interest;life span;Link;Maintenance;Mechanics;Modeling;Molecular;morphogens;Multipotent Stem Cells;Neural Crest;novel therapeutic intervention;Nuclear;Nuclear Lamina;Pathologic;Patients;Physiological;Positioning Attribute;programs;recruit;Regulation;Repressor Proteins;Resolution;Shapes;shift work;Signal Transduction;spatiotemporal;superresolution imaging;Therapeutic;Three-Dimensional Imaging;Tissues;transcription factor;Vision;Work

PROJECT_TITLE: Deciphering how 3D genome organization orchestrates cardiac cellular identity


NIH_SPENDING_CATS: Physical Rehabilitation;Rehabilitation

ORG_CITY: KANSAS CITY

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE This unique program provides interdisciplinary predoctoral training for future basic and clinical scientists in the rapidly evolving field of neurorehabilitation. The program will help ensure that both bench scientists and health care workers are prepared to fully and rapidly exploit the exciting new discoveries now emerging in this dynamic field. Effective treatments for neurological conditions will only be developed through interdisciplinary team science as modeled in this program.

PI_NAMEs: NUDO, RANDOLPH J. (contact)

PROGRAM_OFFICER_NAME: NITKIN, RALPH M

PROJECT_TITLE: Kansas University Training Program in Neurological and Rehabilitation Sciences


NIH_SPENDING_CATS: Biotechnology;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Networking and Information Technology R&D (NITRD);Prevention

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

PHR: Project Narrative This project aims to develop and apply advanced statistical and computational methods to empower the integrative analysis of large scale whole genome sequencing studies (WGS) and biobanks. These methods will advance prevention and intervention strategies in common diseases, such as heart and lung diseases. We will improve the power of rare variant association studies through ensemble testing and the incorporation of cell- type specific functional annotations, and ensemble meta-analysis; developing distributed methods for analyses of large scale WGS studies and federated biobanks; and constructing polygenic risk scores using both common and rare variants, and studying the causal effects of biomarkers and omics markers on diseases and traits by using both common and rare variants in WGS studies and biobanks.

PI_NAMEs: LIN, XIHONG  (contact)

PROGRAM_OFFICER_NAME: WOLZ, MICHAEL

PROJECT_TERMS: Address;biobank;Biological Markers;catalyst;cell type;Cells;Cellular Assay;Cloud Computing;cloud platform;cluster computing;Code;Complex;Computer software;Computing Methodologies;Data;data privacy;Data Set;Disease;disorder risk;Electronic Health Record;empowerment;Environment;Epidemiology;European;European ancestry;exome;Face;FAIR principles;Genetic;Genetic Research;Genetic study;genetic variant;Genome;genome sequencing;genome wide association study;health disparity;Heart Diseases;improved;Individual;Institution;interest;Intervention;learning strategy;Lung Diseases;Mendelian randomization;Meta-Analysis;Methods;Modeling;multi-ethnic;National Heart, Lung, and Blood Institute;National Human Genome Research Institute;Nature;Pathway interactions;Performance;polygenic risk score;Population;power analysis;Prevention strategy;Principal Component Analysis;privacy protection;programs;rare variant;Research;research study;Risk Factors;risk prediction;Sample Size;Sampling;statistical learning;Statistical Methods;Structure;System;Testing;trait;Trans-Omics for Precision Medicine;Underrepresented Populations;United States National Institutes of Health;Untranslated RNA;user friendly software;Variant;Veterans;whole genome

PROJECT_TITLE: Statistical Methods for Integrative Analysis of Large-Scale Multi-Ethnic Whole Genome Sequencing Studies and Biobanks of Common Diseases


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cachexia;Cancer;Digestive Diseases;Neurosciences;Nutrition;Orphan Drug;Pancreatic Cancer;Prevention;Rare Diseases

ORG_CITY: PORTLAND

ORG_DEPT: PEDIATRICS

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Involuntary weight loss, anorexia, fatigue, and cognitive decline are common in patients with cancer. New research demonstrates that these problems limit quality of life for many patients, and also are a significant contributor to risk of death. Our studies are designed to investigate the ways in which cancer leads to these disabling changes in behavior and metabolism to better understand how this might be treated.

PI_NAMEs: ZIMMERS, TERESA A (contact)

PROGRAM_OFFICER_NAME: WATSON, JOANNA M

PROJECT_TERMS: Acute;Address;Adipose tissue;Agonist;Amplifiers;Animals;Anorexia;appetite loss;Attenuated;Automobile Driving;Bacterial Infections;Behavior;Behavioral;Blood - brain barrier anatomy;Body Weight decreased;Bone Marrow;Brain;Cachexia;Cancer Cachexia;Cancer Patient;cancer prevention;cancer therapy;cancer type;cell transformation;Cells;Central Nervous System;Central Nervous System Neoplasms;central nervous system vasculature;Cerebral endothelium;Chronic;Chronic Disease;Collaborations;Data;Dedications;design;Desire for food;Development;Disabling;Disease;drug development;Encephalitis;Endocrine;Event;Evolution;Fatigue;Goals;Growth;Hippocampus;Hypothalamic structure;Immune;Impaired cognition;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Response;Injury;Intervention;Iron;Laboratories;LCN2 gene;Lethargies;Life;Malignant Neoplasms;Melanocortin 4 Receptor;melanocortin receptor;Metabolic;Metabolism;Morbidity - disease rate;mortality risk;motivated behavior;Motivation;mouse model;Muscle;Muscular Atrophy;Myeloid Cells;neural circuit;Neurocognitive;Neurocognitive Deficit;Neuroendocrinology;neuroinflammation;Neurologic;Neurons;neurotoxic;neurotoxicity;new therapeutic target;novel;nutrition;Pancreatic Ductal Adenocarcinoma;pathogen;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Peripheral;Pharmacologic Substance;Physiological;Population;Prevention;Process;Production;Proliferating;Protein Secretion;Proteins;Publications;Quality of life;Reagent;Receptor Signaling;recruit;Research;Research Design;resilience;response;Role;sensor;Series;Sick Role;Signal Pathway;Signal Transduction;Sterility;Stroke;Sympathetic Nervous System;Symptoms;Systemic disease;Testing;Therapeutic Intervention;therapeutic target;therapeutically effective;Tissues;Toxic effect;tumor growth

PROJECT_TITLE: PQ6: Lipocalin-2 as a therapeutic target for prevention of cancer cachexia


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences;Pediatric;Substance Misuse;Underage Drinking

ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Alcohol addiction is a neurological disease that affects millions of individuals in the U.S. and worldwide for which the efficacy of current pharmacological treatments remains limited. To improve such treatments, a better understanding of the long-lasting changes in neuronal communication that occur following chronic alcohol exposure is critical.  It has been theorized that the transition from casual to compulsive drinking is driven by poor decision-making, a phenomenon particularly strong during adolescence and whose influence diminishes with age. The initial loss of control over alcohol consumption may be caused by the weakening of the frontocortical-reflective system, and by the concomitant strengthening of the amygdala-impulsive system.  The objective of this project is to test the existence of a cellular correlate of this theory in the nucleus accumbens (NAc) by examining how nucleus accumbens medium spiny neurons compute competing cognitive and emotional information coming from the prefrontal and amygdala regions, respectively, and how binge alcohol drinking controls this phenomenon.  To explore this question, we will combine in vitro patch-clamp recordings, 2-photon laser scanning microscopy, and a novel double-optogenetics technique in naive and alcohol treated wild-type and transgenic mice.

PI_NAMEs: MARTIN, GILLES E (contact)

PROGRAM_OFFICER_NAME: CUI, CHANGHAI

PROJECT_TERMS: Acute;Adolescence;Adolescent;Affect;Affective;Age;age effect;age related;Alcohol consumption;Alcohol dependence;alcohol effect;alcohol exposure;Alcohols;Amygdaloid structure;Animals;Behavior;binge drinking;biophysical techniques;Brain;Chronic;Cognitive;cognitive computing;Communication;Consumption;Darkness;Data;Decision Making;drinking;drug of abuse;Electrophysiology (science);Emotional;Equilibrium;executive function;experimental study;Glutamates;Goals;hippocampal pyramidal neuron;improved;Impulsivity;In Vitro;Individual;insight;Judgment;Laboratories;Laser Scanning Microscopy;Link;Mediating;Modeling;mouse genetics;Mus;Nervous System Disorder;neural circuit;neurochemistry;neuronal excitability;Neurons;novel;Nucleus Accumbens;Opsin;optogenetics;patch clamp;Pathway interactions;Pharmaceutical Preparations;Pharmacological Treatment;Phase;Play;Prefrontal Cortex;Process;Property;Prosencephalon;Research Support;Rewards;Role;Signal Transduction;Slice;Stimulus;Structure;Synapses;System;Techniques;Testing;theories;Transgenic Mice;transition to adulthood;Translating;two-photon;vulnerable adolescent

PROJECT_TITLE: Effects of binge alcohol drinking on synaptic computing in the nucleus accumbens


NIH_SPENDING_CATS: Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative Thrombopoietin (TPO), a plasma glycoprotein that stimulates platelet production, has been shown to be regulated at the transcriptional level and at the level of its plasma clearance. This project will utilize human derived cell lines and mouse genetics models to dissect the mechanisms of TPO regulation at the level of its intracellular trafficking/secretion and at the level of its intracellular degradation, two previously unrecognized mechanisms of TPO regulation. Knowledge gained from this proposal may lay the foundation for the development of novel strategies to therapeutically regulate the plasma TPO level.

PI_NAMEs: KHORIATY, RAMI  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Animals;Autophagocytosis;autosome;Binding;Biological;Birth;Blood Platelets;Bone Marrow;Cell Line;Cell Maintenance;Cell Maturation;Cell Proliferation;Cell Surface Receptors;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Co-Immunoprecipitations;Complex;Defect;design;Development;Disease;Dose;Endoplasmic Reticulum;Exhibits;experimental study;extracellular;Failure;Flow Cytometry;Foundations;gain of function mutation;Genetic;Genetic Models;Genetic Transcription;genome-wide;Germ Lines;Glycoproteins;Hematopoietic;Hematopoietic stem cells;Hepatocyte;HepG2;Histology;Human;Immunofluorescence Immunologic;Impairment;Interleukin-6;Knock-out;Knowledge;Liver;loss of function mutation;Lysine;Mediating;Megakaryocytes;Membrane;Messenger RNA;mouse genetics;multicatalytic endopeptidase complex;Mus;novel;novel strategies;overexpression;Physiological;Plasma;Platelet Count measurement;Play;Production;progenitor;Proteins;receptor;Regulation;response;Ribosomes;Role;secretory protein;stem cell survival;Testing;Therapeutic;Thrombocytopenia;thrombocytosis;Thrombopoietin;trafficking;Transcriptional Regulation;ubiquitin-protein ligase;Ubiquitination;Validation;validation studies

PROJECT_TITLE: The regulation of thrombopoietin levels

STUDY_SECTION: HT

STUDY_SECTION_NAME: Hemostasis and Thrombosis Study Section.  Committee was terminated on 11/30/2020. [HT]


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Nearly all glioblastomas go through an accelerated growth phase initiated by the onset of necrosis, which proceeds quickly to death. Despite this, little is known about the mechanisms by which necrosis restructures the tumor microenvironment (TME) to drive this fatal expansion, in large part because an appropriate animal model has not been available. We are developing novel mouse models that allow us to induce necrosis within a high-grade glioma in order to directly visualize and analyze its effect on glioma dynamics and growth. In particular we focus on 1) glioma cell migration; 2) glioma stem cell (GSC) localization and accumulation; and 3) the influx of tumor-associated macrophages (TAMs). An improved model that parallels the human disease will demonstrate how these TME elements impact tumor expansion and could potentially be antagonized by novel therapies.

PI_NAMEs: BRAT, DANIEL J (contact)

PROJECT_TERMS: 3-Dimensional;Acceleration;angiogenesis;Animal Model;Animals;antagonist;Automobile Driving;Biological;Brain;Brain Neoplasms;CD34 gene;cell motility;cell type;Cells;Cessation of life;clinically relevant;Coagulation Process;Complex;cranium;CXCR4 gene;Data;Development;Disease Outcome;Disease Progression;Elements;Etiology;Event;Evolution;Genetic;Genetic Transcription;Glioblastoma;Glioma;Growth;Human;human disease;Hypoxia;Immune;Immune system;Immunocompetent;improved;improved outcome;In Vitro;in vivo;Infiltration;innovation;Investigation;Label;Lasers;Link;Literature;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Mesenchymal;Methods;Microscope;Microscopic;microsystems;migration;Modeling;Molecular;monocyte;mouse model;multiphoton microscopy;Mus;Mutation;Necrosis;Necrosis Induction;NF1 mutation;novel;novel therapeutics;patient derived xenograft model;Patients;Pattern;PDGFB gene;Phase;photoactivation;Primary Brain Neoplasms;Process;Proliferating;Property;Radial;Radial Growth Phase;radiation resistance;recruit;Recurrence;Role;Rose Bengal;Sampling;segregation;Shapes;Signal Transduction;spatiotemporal;stem cells;stemness;targeted treatment;Textbooks;Therapeutic;Therapeutic Intervention;therapeutic target;therapeutically effective;therapy development;therapy resistant;Thrombosis;Time;time use;TP53 gene;translational applications;tumor;Tumor Cell Migration;Tumor Expansion;tumor growth;tumor microenvironment;Tumor-associated macrophages;tumorigenic;Up-Regulation;Vascular blood supply;Visualization;Xenograft procedure

PROJECT_TITLE: Modeling the Glioblastoma Microenvironment to Uncover Progression Mechanisms and Therapeutic Targets

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


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

ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: PROJECT NARRATIVE Recovery from hematopoietic injuries, which include significant bleeding, overwhelming infection, radiation exposure and myelosuppressive therapy, will benefit from strategies that modulate hematopoietic stem cell activation and return to quiescence. The proposed research contributes to human health by increasing the understanding of the molecular and cellular mechanisms responsible for the tight regulation of hematopoietic stem cell quiescence signaling within the bone marrow. Knowledge of the basic mechanisms that regulate hematopoietic stem cell quiescence within the bone marrow will aid in the identification of therapeutic targets that improve the regeneration response to hematologic injury, significantly improving overall patient outcomes from hematopoietic stresses.

PI_NAMEs: GILLETTE, JENNIFER  (contact)

PROGRAM_OFFICER_NAME: GILLASPY, ALLISON

PROJECT_TERMS: Adhesions;Attenuated;Biochemistry;Bone Marrow;Cadherins;Cell Communication;Cell Cycle;Cells;combinatorial;Complex;Coupled;Data;Development;exhaustion;Family;Foundations;genetic manipulation;Hand;Health;Hematology;Hematopoietic;hematopoietic stem cell quiescence;Hematopoietic stem cells;Hematopoietic System;Hemorrhage;Human;Image;imaging approach;Imaging Techniques;improved;Individual;Infection;Injury;innovation;insight;Integrins;KAI1 gene;Knock-out;Knockout Mice;Knowledge;Ligands;Light;Link;Mediating;Membrane;Molecular;mouse model;mutant;Mutation Analysis;Myelosuppressive Therapy;Natural regeneration;neutralizing antibody;novel;Patient-Focused Outcomes;Phenotype;prevent;protein protein interaction;Publishing;Radiation exposure;receptor;Receptor Signaling;Recovery;recruit;Regenerative capacity;Regenerative response;Regulation;Research;response;Role;scaffold;Scaffolding Protein;Signal Transduction;single molecule;spatiotemporal;stem cell niche;stem cell self renewal;Stress;Testing;Therapeutic;therapeutic target;Tissues;trafficking;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;Transforming Growth Factors;transplantation therapy;Work

PROJECT_TITLE: Functional Role of Tetraspanin CD82 in Hematopoietic Stem Cell Interactions

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Project Narrative The overall goal of this proposal is to understand and target cancer cell addictions to stress- tolerance pathways. We have identified that many different cancer cells employ translesion synthesis (TLS) to replicate in a continuous manner and subvert the replication stress response. Here, we will implement state-of-the-art assays to analyze how TLS alters DNA replication fork dynamics, replisome components, and identify cancers dependent on TLS in order to fully develop the anti-cancer potential of our lead small molecule inhibitors of TLS.

PI_NAMEs: CANTOR, SHARON B (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: addiction;anti-cancer;anti-cancer therapeutic;Antineoplastic Agents;biological adaptation to stress;Biological Assay;Biological Markers;biomarker identification;cancer cell;Cancer cell line;cancer therapy;Cell Aging;Cell Survival;Cells;Collection;combination cancer therapy;Databases;Dependence;Development;DNA;DNA biosynthesis;DNA Damage;DNA fiber assay;DNA replication fork;DNA Replication Inhibition;Effectiveness;Electron Microscopy;experimental study;Future;gene synthesis;Genes;genome integrity;Goals;Immunoblot Analysis;improved;in vivo;inhibitor;insight;Knowledge;Lead;Malignant - descriptor;Malignant Neoplasms;Measures;Modeling;novel;Oncogenes;Pathway interactions;Patient-Focused Outcomes;Pharmaceutical Preparations;preclinical study;preservation;prevent;Proliferating;Property;Proteins;Proteomics;replication stress;Research;response;scaffold;screening;single molecule;Single-Stranded DNA;small molecule;small molecule inhibitor;Stress;stress tolerance;Structure-Activity Relationship;System;targeted cancer therapy;targeted treatment;Testing;Therapeutic;tool;tumor growth;tumor progression;tumorigenesis

PROJECT_TITLE: Targeting replication stress avoidance in cancer

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Cryptococcosis is a fungal infection that predominantly affects immunosuppressed individuals such as patients with AIDS. A major problem in cryptococcosis is the accumulation of capsular polysaccharide in tissue, which cause local immunosuppression and interfere with the ability of the immune system to clear the infection. The goal of this proposed research program is to develop catalytic antibodies to degrade the capsular polysaccharide in the tissue of AIDS patients as a new therapeutic approach.

PI_NAMEs: CASADEVALL, ARTURO  (contact)

PROGRAM_OFFICER_NAME: LIU, BAOYING

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Affect;AIDS-Related Cryptococcosis;Anthrax disease;anti-fungal agents;anti-microbial drug;Antibodies;Antibody Binding Sites;antibody engineering;Antibody Formation;Antibody Therapy;Antibody-mediated protection;Antigen-Antibody Complex;Antigens;antimicrobial;antiretroviral therapy;Asthma;Basic Science;Binding;Biological;Biological Response Modifier Therapy;capsule;Catalysis;Catalytic Antibodies;Catalytic Domain;Cell surface;Cells;Central Nervous System;Cessation of life;Clinical;Collection;Communicable Diseases;Complement Activation;cost;Crohn's disease;Cryptococcosis;Cryptococcus;Cryptococcus neoformans;Darkness;Deposition;Disease;Dose;drug efficacy;Epidemic;Epitopes;Etiology;Excision;experimental study;fungus;Future;Goals;Hematuria;HIV;HIV Infections;HIV Seronegativity;HIV Seropositivity;Host Defense;Human;human monoclonal antibodies;Hydrolysis;Hydrophobic Surfaces;immune reconstitution;Immune response;Immune system;Immunity;Immunodeficient Mouse;Immunoglobulins;immunosuppressed;Immunosuppression;improved;In Vitro;Individual;Infection;Inflammation;Inflammatory;Learning;Licensing;Malignant Neoplasms;Maps;Mediating;Medicine;Meningoencephalitis;Modality;Modern Medicine;Monoclonal Antibodies;Morbidity - disease rate;mortality;mouse model;Mus;Mycoses;natural antibodies;novel therapeutic intervention;novel therapeutics;Pathogenesis;pathogenic fungus;Patients;Phagocytosis;Phase I/II Trial;Physicians;Polysaccharides;Positioning Attribute;Predisposition;Prevalence;Prevention;programs;Property;Pseudomembranous Colitis;Reagent;Reporting;Research;Resistance;Respiratory syncytial virus;response;Rheumatism;Rheumatoid Arthritis;Risk;Safety;Serum;Site;Site-Directed Mutagenesis;Syndrome;Therapeutic;Time;Tissues;tool;Toxic effect;Variant;Virulence;Visit;Work

PROJECT_TITLE: Exploiting antibody catalysis for treating Cryptococcosis

STUDY_SECTION: HCAC

STUDY_SECTION_NAME: HIV Coinfections and HIV Associated Cancers Study Section[HCAC]


NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Genetics;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Women's Health Research

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: Narrative. In the United States, breast cancer is the most commonly diagnosed cancer among women and still accounts for over 40,000 deaths each year. The underlying goals of this proposal are to identify, at the molecular level, anti-neoplastic strategies that target breast cancer stem cells/tumor initiating cells and to take advantage of tumor cell selective metabolic processes to ultimately lessen disease related mortality.

PI_NAMEs: WALTZ, SUSAN E (contact);WELLS, SUSANNE I

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: advanced breast cancer;aggressive breast cancer;Animal Model;Antineoplastic Agents;beta catenin;Biochemical Pathway;Biological Markers;Biological Process;Biology;Breast Cancer Cell;Breast Cancer Model;Breast Cancer Patient;Breast Cancer Prevention;breast cancer progression;Breast Cancer Treatment;cancer cell;Cancer Cell Growth;cancer diagnosis;Cancer Prognosis;cancer recurrence;cancer stem cell;cancer subtypes;cancer survival;cancer therapy;candidate identification;candidate marker;Carbon;Catabolic Process;Cell Compartmentation;Cell Culture Techniques;cell growth;cell motility;Cell Physiology;Cells;Cessation of life;chemotherapy;Cholesterol;cholesterol biosynthesis;Cholesterol Homeostasis;Chromatin;Clinical;clinically relevant;Coupled;Data;Death Rate;DEK gene;Detection;Disease;Distal;Distant Metastasis;Drops;Enzymes;ERBB2 gene;Estrogen receptor positive;Gene Expression Profiling;Gene Expression Regulation;Genetic;Genus Hippocampus;Glycolysis;Goals;Growth;hormone therapy;Human;in vivo;Individual;insight;Joints;knowledge of results;Laboratories;Link;macromolecule;Malignant Breast Neoplasm;Mammary Neoplasms;Maps;Mediator;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Metastatic breast cancer;Metastatic/Recurrent;Molecular;mortality;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;Nitrogen;novel;Nuclear;Nutrient;Oncogenes;Outcome;overexpression;Pathway interactions;Patients;Phenotype;Population;pre-clinical;Prevention;Preventive measure;Preventive treatment;Process;Production;Prognosis;programs;Property;Proteins;Publishing;Receptor Protein-Tyrosine Kinases;Recommendation;Recurrence;Recurrent disease;Recurrent tumor;Reporting;Resistance;Resolution;response;risk prediction;Role;Sampling;Scientist;self-renewal;side effect;Signal Transduction;sobriety;Source;Specimen;stable isotope;stem-like cell;Testing;Therapeutic;tool;Transcription Coactivator;transcription factor;Transcriptional Activation;treatment strategy;tumor;Tumor Biology;tumor growth;tumor initiation;tumor metabolism;tumor progression;United States;Up-Regulation;Woman

PROJECT_TITLE: Defining genetic and metabolic requirements of aggressive breast cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-T(02)M]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Cocaine;Drug Abuse (NIDA only);Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: NEW HAVEN

ORG_DEPT: PSYCHIATRY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Animal studies have shown that cocaine produces long lasting changes in the connections between nerve cells (so-called “synapses”), suggesting that cocaine use disorder (CUD) may be a form of aberrant structural synaptic density. In pilot studies, we have collected preliminary data using 11C-UCB-J positron emission tomography (PET), suggesting, for the first time, that cocaine users have fewer such connections (i.e., lower synaptic density than healthy individuals. The current study proposes to replicate and extend these initial findings in a larger number of subjects using a more definitive longitudinal, within-subject design.

PI_NAMEs: ANGARITA, GUSTAVO ADOLFO (contact)

PROGRAM_OFFICER_NAME: FEDOTA, JOHN RAPHAEL

PROJECT_TERMS: Abstinence;Admission activity;Affect;Age;Alcohol consumption;Animals;Anterior;Award;Basic Science;Behavior;behavioral sensitization;Binding;Brain;Chronic;cingulate cortex;Clinical;clinical translation;Cocaine;cocaine use;Cocaine use disorder;Cocaine Users;cohort;craving;Data;Decision Making;Dendritic Spines;density;design;Development;Disease;drug abstinence;Drug abuse;drug craving;Drug usage;effective therapy;Exploratory/Developmental Grant;Exposure to;follow-up;Frequencies;Glycoproteins;Hospitals;Hour;Human;Image;Impairment;Individual;Inpatients;Intoxication;Measures;Medial;Mediating;Modeling;Monitor;Neurobiology;Neurocognitive;Neurons;Neurosciences Research;nicotine use;novel;Outcome;Outpatients;Pattern;Performance;Pharmaceutical Preparations;Pilot Projects;Plague;Positron-Emission Tomography;preclinical study;Prefrontal Cortex;presynaptic;Principal Investigator;prolonged abstinence;Proteins;Race;radiotracer;Recurrence;Regimen;Regulation;Relapse;Rewards;Rodent;Role;Sample Size;Scanning;Seminal;sex;Specificity;Stimulant;Study Subject;Synapses;synaptic function;Synaptic plasticity;Synaptic Vesicles;Testing;Time;Toxicology;Translations;Urine

PROJECT_TITLE: Aberrant Synaptic Plasticity in Cocaine Use Disorder: A 11C UCB J PET Study

STUDY_SECTION: NPAS

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Lung;Lung Cancer;Orphan Drug;Precision Medicine;Rare Diseases

PHR: Genomic profiling of solid tumor samples is now essential for the diagnosis and clinical management of many cancer types including lung adenocarcinoma, however current approaches for detecting the full spectrum of cancer mutations involve complicated testing methods and often fail due low specimen quantity or quality. In this proposal, we aim to optimize a rapid and robust whole genome sequencing method, ChromoSeq, that provides a genome-wide profile of all cancer mutation types from commonly available fixed biopsy material, and then validate its clinical performance for patients with lung adenocarcinoma.

PI_NAMEs: DUNCAVAGE, ERIC J (contact);SPENCER, DAVID H

PROGRAM_OFFICER_NAME: CHUAQUI, RODRIGO F

PROJECT_TERMS: Accreditation;accurate diagnosis;Affect;Autopsy;Biological Assay;Biopsy;Blood;Bone Marrow;Cancer Center;cancer genomics;Cancer Patient;cancer subtypes;cancer type;Chromosomal Rearrangement;Chromosomal translocation;Chromosomes;CLIA certified;Clinical;Clinical Management;Clinical Research;clinically relevant;clinically significant;Data;Diagnosis;Diagnostic;Diagnostic Procedure;DNA;DNA Sequence Alteration;DNA sequencing;Evaluation;evaluation/testing;Excision;experimental study;Failure;Formalin;Future;Gene Mutation;Genes;genome sequencing;genome-wide;genomic profiles;genomic profiling;Genomics;Goals;High-Throughput Nucleotide Sequencing;improved;In Situ Hybridization;insertion/deletion mutation;Laboratories;Length;leukemia;Libraries;Lung Adenocarcinoma;Malignant neoplasm of lung;Malignant Neoplasms;Marrow;Measures;Methodology;Methods;Modification;Molecular;Molecular Diagnostic Testing;Molecular Profiling;Molecular Weight;Mutation;Myelogenous;Myeloproliferative disease;next generation;novel;novel strategies;Nucleotides;optimal treatments;Paraffin Embedding;Patients;Performance;performance tests;precision medicine;predicting response;Preparation;Procedures;Process;programmed cell death ligand 1;prospective;Protocols documentation;Reagent;research clinical testing;RNA;Running;Sampling;Single Nucleotide Polymorphism;Solid Neoplasm;Somatic Mutation;Specimen;Stains;standard of care;Structure of parenchyma of lung;success;targeted treatment;Techniques;Technology;Temperature;Testing;Time;Tissue Embedding;tissue processing;Tissue Sample;Tissues;tool;tumor;Validation;variant detection;whole genome

PROJECT_TITLE: A Rapid and Comprehensive Approach for Clinical Genomic Profiling in Lung Cancer


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Cancer Genomics;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Racial and Ethnic Minority Health Research;Women's Health Research

ORG_CITY: EL PASO

ORG_NAME: UNIVERSITY OF TEXAS EL PASO

PHR: We recently discovered two similar anti-cancer compounds with potent toxic activity against many types of human cancer cells. In this proposal, we will perform the requisite experiments to determine how the compounds cause death and if they are able to kill human cancers growing in mice. We expect that in the near future, the identified anti- cancer drugs will result in therapeutic agents that can be used alone or in combination with other FDA approved drugs for the treatment of human cancer and help reduce cancer health disparities.

PI_NAMEs: AGUILERA, RENATO J (contact)

PROGRAM_OFFICER_NAME: BERNAL, FEDERICO

PROJECT_TERMS: Affect;African American;African American Women;analog;Animals;anti-cancer;anti-cancer therapeutic;Antibodies;anticancer activity;Antineoplastic Agents;Asian Women;Basic Science;BCL1 Oncogene;Biochemical;Biological Assay;bioluminescence imaging;Breast;Breast Cancer Cell;Breast Cancer cell line;cancer cell;Cancer cell line;Cancer Etiology;cancer health disparity;cancer type;CASP3 gene;Caspase;Cause of Death;Cell Death Induction;Cell Line;Cell membrane;Cells;Clinical Trials;Combination Drug Therapy;Country;cytotoxic;Data;Databases;Diagnosis;differential expression;DNA Fragmentation;Docking;Drug Screening;effective therapy;Exhibits;experimental study;Family;FDA approved;Future;Gene Expression Profile;Gene Expression Profiling;Genes;Goals;high risk;Hispanic;Human;Hypoxia;Immunotherapy;Implant;in silico;in vivo;Induction of Apoptosis;inhibitor;kinase inhibitor;knock-down;Latina;leukemia;Leukemic Cell;Libraries;live cell imaging;Luc Gene;Luciferases;Malignant Breast Neoplasm;Malignant Neoplasms;MDA MB 231;Minority Groups;Mitochondria;Molecular Target;Monitor;Mus;Names;Network-based;novel;novel anticancer drug;Pathway interactions;Pharmaceutical Preparations;Pharmacotherapy;Phosphorylation;Phosphotransferases;Protein Kinase;Proteins;Pyrazoles;Reactive Oxygen Species;Reverse Transcriptase Polymerase Chain Reaction;Role;screening;Signal Transduction;Signal Transduction Pathway;Small Interfering RNA;stable cell line;Testing;Therapeutic Agents;timeline;transcriptome;transcriptome sequencing;transcriptomic profiling;Translating;triple-negative invasive breast carcinoma;tumor;tumor diagnosis;tumor growth;tumor progression;Tumor Suppressor Genes;United States National Institutes of Health;Western Blotting;White Women;Woman;Women's mortality;Xenograft Model

PROJECT_TITLE: Characterization of novel pyrazole compounds with potent anti-cancer activity


ORG_CITY: Chicago

ORG_DEPT: CHEMISTRY

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: Narrative: Wearable sensor systems present a unique opportunity for the continual monitoring of vital signs and health status of an individual, particularly in the case of cardiac health. In this project we describe a new rapid and reagent-free sensor system for the detection and quantification of a wide range of biomolecules. The project deliverables proposed will directly monitor heart failure markers using a wearable patch, offering a new peripheral biochemical monitoring system that will change how cardiac health is assessed in the United States and beyond.

PI_NAMEs: EFIMOV, IGOR R;KELLEY, SHANA O (contact)

PROGRAM_OFFICER_NAME: THAKAR, RAHUL GAUTAM

PROJECT_TERMS: Acute;Adhesions;Adhesives;Adopted;Adult;Affect;American;Anesthesia procedures;Animal Model;aorta constriction;automated analysis;Benchmarking;Biochemical;Biological;Biological Assay;Biological Markers;Biological Monitoring;biomarker identification;biomarker panel;biomaterial compatibility;Blood;Buffers;Bulla;Cardiac health;Caregivers;Cells;Cellular Phone;Charge;Chronic;Chronic Care;Clinic;Clinic Visits;Clinical;Complex;computer code;Computer software;Data;Data Collection;Deposition;Dermis;design;Detection;detection platform;Deterioration;Development;Devices;Diagnosis;Disease;Disease Management;Economics;electrical measurement;Electrocardiogram;Electrodes;Electronics;Engineering;Environmental Monitoring;Enzyme-Linked Immunosorbent Assay;Enzymes;Exhibits;experience;FDA approved;Filtration;flexibility;Gold;Head;Health Personnel;Health Status;Healthcare;Heart failure;heart function;Heart Rate;hospital readmission;Hospitalization;hospitalization rates;Hospitals;Hydrogels;Hydrophobicity;Implant;implantation;implanted sensor;In Situ;In Vitro;in vivo;in vivo monitoring;Individual;Injections;instrumentation;Intercellular Fluid;Interleukin-1 beta;Interleukin-6;Kinetics;Measurement;Membrane;Metals;Methods;Modeling;Molecular;Monitor;monitoring device;monolayer;nano;Natural regeneration;Needles;novel strategies;Nucleic Acids;Operative Surgical Procedures;Oxygen;Patients;Performance;Peripheral;Persons;Pharmaceutical Preparations;Phosphate Buffer;Photoplethysmography;Platinum;Polymers;Population;porous hydrogel;Positioning Attribute;preservation;pressure;prevent;pro-brain natriuretic peptide (1-76);protein biomarkers;Proteins;Protocols documentation;prototype;Pulmonary artery structure;Pump;Rattus;Reagent;Recurrence;remote monitoring;Reporter;Reporting;Risk;Risk Assessment;Running;Saline;Sampling;sensor;sensor technology;Shapes;Site;Skin;smartphone based device;Specificity;Stress;Suction;Surgical Models;System;Technology;Testing;Textiles;Thinness;Time;Titrations;TNF gene;transmission process;United States;Validation;Vertebral column;wearable device;wearable monitor;wearable platform;wearable sensor technology;wireless;wireless transmission;Wistar Rats;Work

PROJECT_TITLE: Reagentless Sensor Technologies For Continuous Monitoring of Heart Failure Biomarkers

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


NIH_SPENDING_CATS: Asthma;Infectious Diseases;Lung

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Public Health Relevance: Fungal asthma is oftentimes poorly controlled with frequent exacerbations and hospitalizations, and it can be fatal. The medications to treat or prevent these complications are limited and have side effects. The completion of this proposal will advance our knowledge about the pathogenesis of fungal asthma, and establish a foundation for the development of IFN therapy to treat asthma.

PI_NAMEs: CHEN, YIN  (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Abbreviations;Acute;Air;airway epithelium;airway hyperresponsiveness;airway mucous cell metaplasia;Alternaria;Animal Model;anti-fungal agents;Aspergillus;Asthma;asthma exacerbation;asthma model;asthmatic;atopy;Bronchoalveolar Lavage;Cells;Chronic;Cladosporium;Clinical;Coin;Data Analyses;Data Set;Detection;Development;Epithelial Cells;Epithelium;Exposure to;Foundations;Fungal Spores;Fungi Model;fungus;Genes;Genetic Polymorphism;genetic signature;Homeostasis;Hospitalization;Human;Immune response;immunogenic;Immunology;Impairment;Individual;Infection;Inflammasome;Inflammation;Integrins;Interferons;Knockout Mice;Knowledge;Link;Lung;Lymphoid Cell;Mediating;Metaplasia;meter;Modeling;Molds;Molecular;Molecular and Cellular Biology;mouse model;Mucous body substance;Mus;National Heart, Lung, and Blood Institute;Natural Immunity;neutrophil;novel;Pathogenesis;Pathway interactions;Pattern;Pattern recognition receptor;Persons;Pharmaceutical Preparations;Phenotype;Prevalence;prevent;Production;programs;public health relevance;pulmonary function;RARRES3 gene;receptor;Reporting;Reproduction spores;Research;resilience;respiratory;response;Risk Factors;RNA;Role;Sampling;Seasons;sensor;side effect;Signal Transduction;single-cell RNA sequencing;statistics;Subcategory;Testing;therapeutic development;TLR3 gene;transcriptomics;type I interferon receptor;United States National Institutes of Health;Viral

PROJECT_TITLE: Fungal Asthma and Lung Innate Immunity

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Neurosciences;Precision Medicine;Skin Cancer

PHR: Although treatments for patients with metastatic melanoma, including inhibitors of PD-1, have had impressive activity in clinical trials, patients with brain metastases have largely been excluded from these trials. We propose to capitalize on resources generated at Yale in recent years to study brain metastasis to develop new therapeutic approaches. We will continue our studies of combinations of immune therapy and VEGF-targeting therapy, by validating exciting clinical trial results and conducting mechanistic studies in animal models as a basis for future clinical trials aimed at improving outcomes for patients with brain metastasis from melanoma or other tumor types.

PI_NAMEs: JILAVEANU, LUCIA BEATRICE (contact);KLUGER, HARRIET M.

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Address;Adhesions;Animal Model;anti-PD-1;Antibodies;Back;bench to bedside;bevacizumab;Blood - brain barrier anatomy;Blood specimen;Blood Vessels;blood-brain barrier function;Brain;cell motility;Cell Physiology;Cells;Central Nervous System;Cephalic;Cerebrum;Characteristics;Clinic;clinical biomarkers;Clinical Research;Clinical Trials;clinically relevant;clinically significant;cohort;Coupled;CTLA4 gene;design;Disease;Drug Combinations;Drug Targeting;early phase clinical trial;Edema;Endothelial Cells;Endothelium;Enrollment;Evaluation;Exclusion;expectation;experimental study;Future;Gene Expression Profile;Human;Immune;Immunity;Immunocompetent;Immunophenotyping;Immunotherapy;improved;improved outcome;In Situ;in vitro Model;Incidence;Infrastructure;inhibitor;Institution;ipilimumab;KDR gene;Lymphocyte;Macrophage;Maintenance;Malignant neoplasm of lung;Melanoma;Melanoma patient;Metastatic malignant neoplasm to brain;Metastatic Melanoma;Methods;Microglia;Modeling;Molecular;Molecular Analysis;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;Neurologic Symptoms;Nivolumab;novel;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;participant enrollment;Pathway interactions;Patient-Focused Outcomes;Patients;PD-1 blockade;PD-1 inhibitors;PD-1 pathway;pembrolizumab;Pharmaceutical Preparations;pharmacologic;phase II trial;Positioning Attribute;pre-clinical;Pre-Clinical Model;preclinical study;predicting response;programmed cell death protein 1;Property;protein expression;Proteomics;Radiation;Radiation necrosis;Regimen;Research Personnel;Resistance;Resources;responders and non-responders;response;Sampling;Series;Signal Transduction;Solid Neoplasm;Specific qualifier value;Specimen;success;System;Systemic Therapy;T-Lymphocyte;targeted treatment;Testing;Therapeutic Effect;Tight Junctions;Toxic effect;trafficking;transcriptomics;treatment response;tumor;Tumor Angiogenesis;tumor growth;tumor microenvironment;Tumor Promotion;Validation;Vascular Endothelial Growth Factors;Vegf inhibition

PROJECT_TITLE: Immune Therapy for Brain Metastasis

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ED_INST_TYPE: HOSPITALS

ORG_CITY: HOUSTON

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: Although metastases are the main cause of colorectal cancer (CRC) deaths, and diet is considered the most important environmental factor for CRC development, we still cannot answer the simple questions, which dietary factors contribute to CRC metastasis and what is the mechanism. Answering these questions is important because, unlike genetic factors, diet can be modified, thereby having immense potential for reducing CRC mortality. In this proposal, we aim to address these fundamental questions by using preclinical models and data on CRC patients’ specimens to test our hypothesis that the consumption of sugar-sweetened beverages containing glucose and fructose, accelerates CRC metastasis.

PI_NAMEs: YUN, JIHYE  (contact)

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: Acceleration;Acute;Address;Adenosine;Adult;Affect;Biological Markers;Blood;Calories;cancer cell;Cancer Etiology;Cause of Death;cell growth;cell motility;Cessation of life;Chronic;clinical practice;Clinical Practice Guideline;colon cancer cell line;colon cancer patients;Colorectal Cancer;colorectal cancer metastasis;colorectal cancer prevention;Complex;Consumption;Data;Databases;Developed Countries;Development;Diabetes Mellitus;Diet;Dietary Factors;dietary guidelines;Dipeptidyl Peptidases;Distant Metastasis;Environmental Risk Factor;Enzymes;epidemiology study;experimental study;Fructose;Genetic;Glucose;Hyperglycemia;in vivo;Incidence;Invaded;Isotopes;Juice;L-Iditol 2-Dehydrogenase;Link;Liquid substance;Mediating;Messenger RNA;Metabolic;Metabolic Pathway;Metabolism;Metastatic Neoplasm to the Liver;Micronutrients;migration;Molecular;mortality;Motility;mouse model;NADH;Neoplasm Metastasis;new therapeutic target;Nutritionist;Obesity;Oncologist;Organoids;Outcome;Pathway interactions;Patients;Persons;Phenotype;Play;polyol;Pre-Clinical Model;Process;protein expression;Proteins;Reaction;Recommendation;Recurrence;response;Role;Sorbitol;Specimen;Sucrose;sugar;Survival Rate;sweetened beverage;Testing;tool;tumor;Xenograft Model;Xenograft procedure;young adult

PROJECT_TITLE: ROLE OF SORD IN SUGAR-MEDIATED CANCER METASTASIS

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: MIAMI

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: FLORIDA INTERNATIONAL UNIVERSITY

PHR: Project Narrative Negative outcomes of behavior problems in early childhood are overrepresented in low-income and underrepresented minority families. We are evaluating the effect of a brief home-based intervention targeting parenting behavior on improvements in behavior and regulation in infants from high-risk families to prevent the need for later, more intensive treatment in childhood. In light of increasing needs and decreasing resources among the most vulnerable families, this research project carries potential for significant public health impact.

PI_NAMEs: BAGNER, DANIEL MARC (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: active control;active control group;Address;aged;Aggressive behavior;Attention;Behavior;Behavioral;behavioral outcome;Child;Child Behavior;Child Development;Child Rearing;Childhood;Clinic;Collaborations;Communities;Data;depressive symptoms;Development;Disadvantaged minority;Distress;dosage;Dropout;early childhood;Early Intervention;Early treatment;economic disparity;efficacy evaluation;Emotional;emotional functioning;Enrollment;Environment;Ethnic Origin;evidence base;Exposure to;Family;follow up assessment;Growth;high risk;high risk behavior;high risk infant;Home;Impairment;improved;indicated prevention;infancy;Infant;Infant Behavior;Infant Development;Infant Health;Intervention;intervention effect;Learning;Light;Low income;Maintenance;Matched Group;Measurement;Measures;Mediating;Mediation;Mediator;Methods;Modeling;National Institute of Child Health and Human Development;negative affect;Neighborhoods;nutrition;Outcome;parental role;parenting intervention;Parents;Pattern;Physiological;pilot test;post intervention;prevent;Prevention;preventive intervention;Primary Care;Problem behavior;programs;Psychopathology;psychosocial adjustment;Public Health;public health priorities;racial minority;Randomized;Randomized, Controlled Trials;Regulation;Reporting;Research;Research Priority;Research Project Grants;Resources;respiratory;Risk Behaviors;Risk Reduction;Role;satisfaction;Science;Sinus Arrhythmia;Source;Stress;Testing;Theoretical model;Therapeutic;Time;Underrepresented Minority;Withdrawal;Work

PROJECT_TITLE: Preventive Intervention for Behavior Problems in Infants from High-Risk Families


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Physical Injury - Accidents and Adverse Effects;Prevention;Substance Misuse

PHR: PROJECT NARRATIVE This experimental study will test the impacts of subsidized ridesharing on drunk driving, alcohol consumption, and mobility. This information is critical because alcohol-involved motor vehicle crashes are a major cause of death and injury, and preliminary studies provide compelling evidence that subsidized ridesharing may be a high-impact prevention strategy. Results of this study will provide important information to guide preventive interventions that use subsidized ridesharing to reduce alcohol-involved crashes—including identifying the individuals who will benefit most substantially and the locations where impacts will be greatest—while minimizing side-effects on alcohol consumption.

PI_NAMEs: MORRISON, CHRISTOPHER NEIL (contact)

PROGRAM_OFFICER_NAME: FREEMAN, ROBERT

PROJECT_TERMS: Advertisements;Affect;Aftercare;aged;alcohol availability;Alcohol consumption;alcohol exposure;alcohol involvement;alcohol risk;Alcohols;arm;Cause of Death;Cellular Phone;Cessation of life;Cities;Control Groups;cost;cost effective intervention;Custom;Data Collection;design;digital;Drunk driving;Eligibility Determination;Engineering;Environment;Equation;Etiology;experimental study;Frequencies;Geography;Goals;group intervention;Health Benefit;Health Care Costs;impaired driving performance;Impairment;improved;Incidence;Income;Individual;injured;Injury;injury burden;Intervention;Licensing;Location;Measures;Medicine;mobile application;Motor Vehicles;Municipalities;Outcome;Participant;Persons;Population;post intervention;Prevention strategy;preventive intervention;Primary Prevention;Privatization;programs;prospective;Public Health;Publishing;Randomized;Randomized, Controlled Trials;recruit;Reporting;Research;Research Design;residence;Risk;Sampling;Shapes;side effect;Single-Blind Study;social media;Surveys;Technology;Testing;theories;therapy design;Time;treatment group;United States;United States National Academy of Sciences;Vehicle crash;voucher;Work

PROJECT_TITLE: Impacts of Subsidized Ridesharing on Drunk Driving, Alcohol Consumption, and Mobility

STUDY_SECTION: CLHP

STUDY_SECTION_NAME: Community-Level Health Promotion Study Section[CLHP]


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Mental Health;Mental Illness;Neurosciences;Women's Health Research

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Despite demonstrated clinical effectiveness of Mindfulness-Based Stress Reduction (MBSR) for anxiety, there remains a gap in knowledge about the brain mechanisms by which MBSR works and the neurobiological mechanism for sex differences in MBSR response for the common condition of Generalized Anxiety Disorder (GAD). GAD is an example of a condition with perturbations in these relevant emotion regulation and attentional neural circuits for whom MBSR has demonstrated efficacy. Building on prior data supporting our hypotheses about MBSR, GAD, and sex differences in fear and extinction neurocircuitry as well as novel whole brain functional connectivity analyses, we propose a rigorous neuroimaging study to examine how MBSR works, focusing on MBSR induced neural mechanisms that drive response to MBSR in patients with generalized anxiety disorder (GAD), and the degree to which sex differences in MBSR response are explained by sex differences in these mechanisms, in line with moving mind body interventions for common problems such as GAD towards precision medicine.

PI_NAMEs: RAIO, CANDACE M;SIMON, NAOMI M (contact)

PROGRAM_OFFICER_NAME: QUINLAN, ERIN BURKE

PROJECT_TERMS: Adherence;Affect;Amygdaloid structure;Animals;Anxiety;anxiety reduction;Attention;attentional control;Awareness;Behavioral;Brain;Brain region;Clinical;Clinical effectiveness;conditioned fear;Conditioned Stimulus;Coupling;Cues;Data;Diagnosis;Education;emotion regulation;Emotional;Emotions;evidence base;Exhibits;Expectancy;Extinction;follow-up;Fright;Functional Magnetic Resonance Imaging;Future;Generalized Anxiety Disorder;Hippocampus;Human;improved;insight;Intervention;Knowledge;Learning;learning extinction;Literature;Measures;Memory;men;Methodology;Methods;Mind-Body Intervention;mind/body;mindfulness-based stress reduction;National Center for Complementary and Integrative Health;neural;neural circuit;neural network;neurobiological mechanism;neuroimaging;neuromechanism;Neuronal Plasticity;novel;Outcome;Participant;Patients;Phase;precision medicine;Prediction of Response to Therapy;predictive modeling;Prefrontal Cortex;Premenopause;Primary Care;Process;Randomized;reduce symptoms;Research;research and development;response;Rest;restoration;rumination;Science;sex;Sex Differences;Standardization;Stress;stress reduction;success;symptomatic improvement;Synapses;Testing;therapy development;Time;treatment response;Woman;Work

PROJECT_TITLE: Elucidating Neural Mechanisms and Sex Differences in Response to Mindfulness Based Stress Reduction in Generalized Anxiety Disorder