NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Endocrine Disruptors;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE Autism spectrum disorder (ASD) is a highly prevalent disease affecting 1 in 54 children in the US and risk to this disease is increased in individuals exposed to environmental chemicals such as BPA. Although mutations in the coding regions of genes affecting protein function have been identified in patients with ASD, the contribution of non-coding variants present in different individuals to ASD phenotypes and their interaction with the environment has not been explored. This study will identify non-coding genome variants that respond to BPA exposure by causing gene expression changes and alterations of neural cell fate similar to those observed in ASD patients, increasing our understanding of how chemicals in the environment may alter brain development in children with autism.

PI_NAMEs: CORCES, VICTOR G. (contact)

PROGRAM_OFFICER_NAME: LAWLER, CINDY P

PROJECT_TERMS: Affect;Age;Air;Alleles;ASD patient;ATAC-seq;autism spectrum disorder;autism symptoms;autistic children;Autopsy;Bar Codes;base;Behavior;Behavioral;Binding;Biological Assay;bisphenol A;Blood;Brain;Brain region;brain tissue;building materials;Cell Differentiation process;Cell Line;Cell Lineage;cell type;Cells;Cerebral cortex;Cerebrovascular system;Cerebrum;Chemicals;Child;Chromatin;Chronic Disease;Code;Collection;combinatorial;Communication;Cosmetics;Dendritic Spines;density;Dependence;Development;Diagnosis;Disease;Endocrine Disruptors;Environment;environmental chemical;exome sequencing;experimental study;exposed human population;Exposure to;Family;Female;Fetal Development;Food;gene environment interaction;Gene Expression;Genes;Genome;genome editing;genome sequencing;genome wide association study;genome-wide;Germ Lines;Goals;gray matter;Growth;Heart Diseases;Household Products;Human;human induced pluripotent stem cells;Impairment;Incidence;Individual;induced pluripotent stem cell;Knowledge;Laboratory Animals;Malignant Breast Neoplasm;Malignant neoplasm of testis;Monitor;Mus;Mutation;nerve stem cell;neural;Neurodevelopmental Disorder;Neuroglia;Neurons;novel;Nuclear Hormone Receptors;Nucleic Acid Regulatory Sequences;Obesity;Organoids;Paper;Pathway interactions;Patients;Penetrance;Phenotype;Plastics;Population;pregnant;Process;programs;protein function;Race;Reporter;Research;response;Risk;Role;Sampling;sex;single nucleus RNA-sequencing;Site;social communication;social integration;Social Interaction;Societies;Testing;Time;transcription factor;Untranslated RNA;Urine;Variant;Water;white matter;whole genome

PROJECT_TITLE: Gene-Environment interactions in Autism


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Pancreatic Cancer;Rare Diseases

ORG_CITY: PITTSBURGH

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Development of new treatment strategies that interfere with RAS oncogene-dependent signaling pathways could greatly improve the outcome of PDAC patients. Successful completion of this study will validate PYK2 as a new functionally relevant and pharmacologically actionable target for PDAC and PYK2–targeted therapy as a novel effective approach to treating PDAC.

PI_NAMEs: HU, JING  (contact)

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: Acinar Cell;anti-cancer research;anticancer activity;antitumor effect;beta catenin;Biological;Cancer Etiology;cancer therapy;carcinogenesis;Cell Line;Cell Reprogramming;Cells;Cessation of life;chemotherapy;cofactor;Cytoplasm;Data;Death Rate;Development;Diagnosis;Disease;druggable target;Duct (organ) structure;gain of function;Genetic;Genetic Transcription;Growth;Heterozygote;Human;improved;improved outcome;In Vitro;inhibitor;interest;Intervention;intestinal tumorigenesis;knock-down;Knock-in Mouse;Knockout Mice;KRAS oncogenesis;KRAS2 gene;KRASG12D;Lesion;Life Expectancy;LoxP-flanked allele;Maintenance;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediator;Metaplasia;Molecular;mouse model;mouse tyrosine kinase 2;Mus;mutant;Mutation;novel;novel strategies;novel therapeutic intervention;Outcome Study;p65;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;Pancreatic Intraepithelial Neoplasia;Pathway interactions;patient derived xenograft model;Patients;pharmacologic;Phosphorylation;Phosphotransferases;pre-clinical;Pre-Clinical Model;preclinical evaluation;premalignant;Protein Tyrosine Kinase;Proteins;PTK2B gene;ras Oncogene;research clinical testing;Role;Serine;Signal Pathway;Signal Transduction;small hairpin RNA;Solid;Survival Rate;targeted treatment;Testing;Text;Therapeutic Intervention;therapeutic target;therapeutically effective;Tissues;tumor growth;Tyrosine;United States;Validation;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Targeting PYK2 for the treatment of PDAC


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Services;Nutrition;Obesity;Prevention

ORG_CITY: PROVIDENCE

ORG_NAME: MIRIAM HOSPITAL

ORG_STATE: RI

PHR: PROJECT NARRATIVE  Forty percent of emerging adults have overweight or obesity; however, emerging adults are underrepresented in traditional weight loss programs, drop-out at high rates, and have blunted weight loss outcomes. In this project, I propose to develop, iteratively adapt, and pilot test a behavioral weight loss intervention designed specifically to optimize feasibility, acceptability, and weight loss in emerging adults as well as be easily disseminable and implementable in college health service settings to improve intervention reach and access. This project will address a critical public health need and explore a novel treatment delivery model to improve weight status in emerging adults in the present that could reduce increasing obesity and related downstream health consequences in later adulthood.

PI_NAMEs: HAYES, JACQUELINE F (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: Acceleration;active control;Address;Adherence;Adult;adult obesity;Age;age group;aged;Award;Behavior;behavior change;behavior test;Behavioral;Benchmarking;Body mass index;Body Weight Changes;Body Weight decreased;Calories;career;Caring;Cognitive;cohort;college;community advisory board;Control Groups;Data;Dedications;design;Development;Disease remission;Dropout;Early treatment;Eating;effective intervention;Effectiveness of Interventions;effectiveness trial;efficacy trial;Eligibility Determination;emerging adult;energy balance;Enrollment;Environment;evidence base;experience;Feedback;flexibility;formative assessment;Future;Goals;Health;Health Services;Hospitals;Hybrids;implementation facilitators;implementation intervention;implementation outcomes;implementation science;improved;Individual;Institution;Intake;Intervention;Intervention Studies;Interview;Life Style;Maintenance;men;Mentored Patient-Oriented Research Career Development Award;Mentors;Methods;Milk;Modeling;Monitor;novel;Obesity;obesity treatment;obesogenic;online delivery;Outcome;Overweight;Persons;pilot test;pilot trial;Population;Populations at Risk;Positioning Attribute;preference;Prevalence;prevent;Proctor framework;prototype;psychoeducation;Public Health;Randomized;recruit;Research;Research Activity;Research Personnel;research study;Risk;Self Efficacy;Series;Service setting;Statistical Methods;Students;Testing;theories;therapy design;Time;Training;Training Activity;Translations;Universities;university student;Weight;weight gain prevention;weight loss intervention;weight loss program;Weight maintenance regimen;Woman;Work;young adult

PROJECT_TITLE: Developing a Behavioral Weight Loss Intervention for Emerging Adults Implemented within College Health Service Centers

STUDY_SECTION: DDK

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


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Brain Disorders;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Pediatric;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Narrative: Structural malformations of the face are common and often exhibit a large degree of morphologic variation; however, the mechanisms underlying variation are not known. Our objective is to examine the mechanistic basis for variable expressivity and penetrance that produce craniofacial malformations.

PI_NAMEs: HALLGRIMSSON, BENEDIKT ;MARCUCIO, RALPH S (contact)

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: Address;Affect;Alleles;Biological Models;Biological Process;Brain;Child;Cleft lip with or without cleft palate;Clinical;Complex;Congenital Abnormality;Craniofacial Abnormalities;Development;Diagnosis;Diagnostic;Disease;Drops;Dysmorphology;Embryo;Event;Exhibits;Face;Failure;FGF17 gene;FGF8 gene;Fibroblast Growth Factor 8;Funding;Gene Expression;gene interaction;Genes;Genetic;Genetic Diseases;Genetic Epistasis;Genetic Variation;Genome;genome-wide;Genomics;Genotype;Goals;Heterozygote;Holoprosencephaly;Homozygote;Human;Human Genome;Image;Individual;innovation;Jaw;Ligase;malformation;Maps;Medical;Medicine;Mendelian disorder;Modeling;Molecular;Molecular Diagnosis;Monoubiquitination;Morphology;multimodality;Mus;mutant;Mutant Strains Mice;Mutation;Nitric Oxide Synthase;null mutation;Outcome;overexpression;Pathway interactions;Patients;Penetrance;Phase;Phenotype;Post-Translational Protein Processing;Probability;Process;Prognosis;prognostic;programs;Prosencephalon;Proteins;Quantitative Trait Loci;Rare Diseases;rare genetic disorder;Research;Role;Secure;Series;Shapes;SHH gene;Signal Transduction;single-cell RNA sequencing;Structural defect;Symptoms;Testing;theories;Therapeutic;Tissues;trait;transcriptomics;Translating;ubiquitin-protein ligase;Variant;Work

PROJECT_TITLE: The role of continuous phenotypic variation in structural defects of the face


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: WALTHAM

ORG_DEPT: BIOLOGY

ORG_NAME: BRANDEIS UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative  Neurons must constantly rebuild themselves as the membrane proteins that give rise to synaptic connectivity and electrical excitability are replaced. At the same time, brain circuits must be stable. The goals of this project are to understand how individual animals achieve robust function over time in the face of the need to respond flexibly to environmental perturbations.

PI_NAMEs: MARDER, EVE E (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Address;Animals;Behavior;Biological;Brain;Compensation;Computer Models;Crustacea;experimental study;flexibility;Funding;Future;Ganglia;Goals;Human;Individual;Invertebrates;Ion Channel;Measures;Membrane Proteins;Modeling;National Institute of Neurological Disorders and Stroke;Nervous System;Neuromodulator Receptors;Neurons;neuroregulation;receptor;Regulation;response;Synapses;Temperature;Time;Work

PROJECT_TITLE: Neuromodulation and Robustness of Neurons and Networks


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Clinical Research;Congenital Structural Anomalies;Digestive Diseases;Genetics;Human Genome;Liver Disease;Pediatric;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Project Narrative Because our understanding of hepatobiliary disease is incomplete, a significant number of children with biliary tree dysgenesis and liver disease have nondiagnostic genetic testing. The goal of this research proposal is to improve the diagnosis and care of children and adults with liver and biliary disease by better characterizing the genetic landscape of these conditions. To accomplish this goal, we will assemble and characterize a large cohort of patients with biliary and liver disease and apply a research pipeline for gene discovery and validation, with additional focus on MED12 as a novel biliary dysgenesis gene.

PI_NAMEs: STRONG, ALANNA  (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Acute Liver Failure;Adult;Advisory Committees;Animal Model;Applications Grants;Autoimmune;Award;beta catenin;Biliary;Biliary Atresia;biliary tract;Biological Assay;Candidate Disease Gene;candidate selection;career;career development;Cell Line;Cell model;Child;Child Care;Childhood;cholangiocyte;Cholestasis;cleft lip and palate;Clinical;clinical diagnosis;Clustered Regularly Interspaced Short Palindromic Repeats;Code;cohort;Complex;Computerized Medical Record;congenital hepatic fibrosis;Copy Number Polymorphism;Data;Defect;Development;Diagnosis;Disease;Ethylnitrosourea;Etiology;exome;exome sequencing;experience;Experimental Designs;Faculty;Fellowship;Fibrosis;Filtration;Functional disorder;Future;Gastroenterology;gene discovery;Gene Expression;Genes;Genetic;genetic disorder diagnosis;genetic testing;Genetic Transcription;genetic variant;Genomics;Goals;Grant;Hardikar syndrome;Hepatic;Hepatobiliary;Hepatology;Hepatopancreas;Heterozygote;Human Genetics;Immunofluorescence Immunologic;improved;Individual;Intellectual functioning disability;Intestines;K-Series Research Career Programs;Laboratories;Lead;Learning;Life;Literature;Liver;Liver diseases;Liver Dysfunction;malformation;Mediator;Medical Genetics;Medicine;Mentors;Messenger RNA;Metabolic;Microscopy;Modeling;Morbidity - disease rate;Morphology;mortality;mutant;Mutation;neurogenetics;notch protein;Notch Signaling Pathway;novel;novel therapeutic intervention;novel therapeutics;Online Mendelian Inheritance In Man;Paper;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pattern;Pediatric Hospitals;pediatric patients;Pediatrics;Pennsylvania;Phenotype;Philadelphia;Physicians;Population;Postdoctoral Fellow;professor;Proteins;Reagent;Recording of previous events;Reporting;Research;Research Proposals;Residencies;Resources;Retinal Diseases;RNA Polymerase II;Role;Running;Scientist;Signal Transduction;Standardization;Structure;Syndrome;Testing;TGFB1 gene;Training;transcription factor;Universities;urinary tract obstruction;Validation;Variant;Western Blotting;Work;Writing;X-linked intellectual disability;Zebrafish

PROJECT_TITLE: Novel gene discovery in disorders of the liver and biliary tree


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_CITY: BALTIMORE

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE  The loss or damage of sensory cells in the inner ear, specifically the outer hair cells (OHCs), is a critical cause of age-related and noise-induced hearing loss, which are now worldwide epidemics. This competitive renewal builds on our success in identifying transcription factors critical for the functional maturation and survival of OHCs to now define their role within the OHC genetic program. Successful completion of this research will: impact our understanding of inner ear sensory cell development and survival; advance research on the molecular basis of age-related hearing loss; and, inform the design of future therapeutic interventions such as hair cell regeneration therapy.

PI_NAMEs: AHMED, ZUBAIR M. (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Address;Age;Bioinformatics;Biological;Candidate Disease Gene;candidate identification;Cell Differentiation process;Cell Maturation;Cell Physiology;Cell Survival;cell type;Cells;Cellular biology;cilium biogenesis;Cochlea;Communities;Compensation;conditional knockout;Data;Data Set;Defect;design;Development;Disabling;Disease;Ear;Embryo;Epidemic;Epigenetic Process;Equilibrium;follow-up;Funding;Future;Gene Expression;Gene Expression Profiling;Genes;Genetic;Genetic study;Genetic Transcription;Genomics;GFI1 gene;Goals;Grant;Hair;hair cell regeneration;Hair Cells;Hearing;hearing loss treatment;Hour;Human;Informatics;inner ear development;International;Intervention;Knockout Mice;Knowledge;Labyrinth;Lead;Letters;Maintenance;Maps;Modeling;Molecular;molecular targeted therapies;mouse model;multiple omics;Mus;Mutagenesis;Names;Noise-Induced Hearing Loss;novel;Outer Hair Cells;Pathology;Pathway interactions;Phenotype;Play;Population;postnatal;Presbycusis;prevent;Process;Production;programs;Protocols documentation;regenerative therapy;Regulator Genes;Research;Research Personnel;RFX1;RiboTag;Role;Route;Running;Sensory;Sensory Hair;Signal Pathway;Signal Transduction;stem cell fate;stem cells;success;Testing;Therapeutic Intervention;tool;transcription factor;transcriptomics;translatome;Vestibular Hair Cells;vestibular system;Visualization;Work;Zebrafish

PROJECT_TITLE: Cell Type Specific Transcriptional Cascades in Inner Ear Development

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: ROCHESTER

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Project Narrative Human hearing is characterized by high sensitivity and high frequency-selectivity. Unfortunately, this hearing function is fragile. A prominent signature of hearing loss is damage of outer hair cells, which can result in 40-60 dB of hearing loss. This project has Relevance to Public Health because it holds the promise to improve quality of life in individuals suffering hearing difficulty by identifying how outer hair cells operate to amplify small sounds. The project uses state-of-art measurement methods and computational simulations to quantify key unknowns related to the function of the outer hair cells.

PI_NAMEs: NAM, JONG-HOON  (contact)

PROGRAM_OFFICER_NAME: CYR, JANET

PROJECT_TERMS: Address;Adult;Affect;Animals;Apical;Basilar Membrane;biophysical properties;Biophysics;Cell Communication;cell motility;Cell Physiology;Cells;Chemicals;Cochlea;Collagen Fiber;Complex;Computer Models;computer program;Computer Simulation;Data;design;electric impedance;Electric Stimulation;electrical potential;Ensure;Epithelium;experience;experimental study;Frequencies;Functional disorder;Hair Cells;Hearing;hearing impairment;Human;Image;improved;In Situ;In Vitro;in vivo;Individual;Labyrinth;Link;Liquid substance;Location;Measurement;Measures;mechanical properties;Mechanical Stimulation;Mechanics;mechanotransduction;Methods;Modeling;Molecular;Motion;neural;neuronal cell body;novel;Optical Coherence Tomography;Organ;Organ of Corti;Organelles;Outcome;Outer Hair Cells;Physics;Play;Property;Public Health;Quality of life;Radial;Research;Resolution;response;Role;Science;Scientist;Sensory;Series;Side;sound;Specific qualifier value;Structure;Supporting Cell;System;Techniques;tectorial membrane;Testing;theories;tool;transmission process;United States;Velocimetries;vibration;virtual

PROJECT_TITLE: The Role of the Organ of Corti for Cochlear Power Transmission


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Bioengineering;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Nanotechnology

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Our long-term goal is to understand the molecular and cellular events that underlie the formation and growth of unstable atherosclerotic plaques in blood vessels, which can cause heart attacks and strokes. These medical conditions represent the leading cause of death worldwide and are highly-relevant to the mission of the NIH. In particular, we are investigating how arterial inflammation and endothelial cell dysfunction contribute to the formation of vulnerable plaques with the goal of identifying new therapeutic targets to treat atherosclerosis.

PI_NAMEs: CHEN, HONG  (contact);SHI, JINJUN ;SHYY, JOHN YJ

PROGRAM_OFFICER_NAME: PLAYFORD, MARTIN P

PROJECT_TERMS: Acceleration;Adaptor Signaling Protein;Advanced Development;Animal Model;Aorta;ApoE knockout mouse;Apolipoprotein E;Arterial Fatty Streak;Artificial nanoparticles;atherogenesis;atheroprotective;Atherosclerosis;Binding;Biological Availability;Birth;Blood Vessels;Breeding;Cardiovascular Diseases;Cause of Death;Cell Physiology;Cells;Clathrin;clinically relevant;clinically significant;combat;Complement;Complex;Curiosities;Data;Development;disabled;Disabled Homolog 2 Protein;effective therapy;Endocytosis;Endosomes;Endothelial Cells;endothelial dysfunction;Endothelium;Ensure;epsin;Event;Exhibits;Foundations;Functional disorder;Gene Activation;Gene Expression;Genes;Goals;Growth;Health;Heart Diseases;Human;Immune;Impairment;In Vitro;Inflammation;Inflammatory;inhibitor;innovation;Interleukin-6;Investigation;Knockout Mice;Lesion;Low-Density Lipoproteins;MAP4;Mediating;Medical;Messenger RNA;Microscopy;Mission;Modeling;Molecular;Morbidity - disease rate;mortality;mRNA delivery;Mus;Myocardial Infarction;nanoparticle;Nanotechnology;new therapeutic target;NOS3 gene;novel;novel therapeutics;oxidized low density lipoprotein;particle;Pathway interactions;Patients;Phosphotransferases;PIK3CG gene;Pilot Projects;Play;prevent;Production;Proteins;Quantitative Reverse Transcriptase PCR;Reagent;recruit;Reporting;Research;Resolution;response;restraint;Risk;Role;Rupture;sharpin;shear stress;Signal Pathway;Signal Transduction;stem;Stroke;targeted delivery;Technology;Testing;Therapeutic;TNF gene;trafficking;transcriptome sequencing;Tumor Suppressor Proteins;Ubiquitin;Ubiquitination;United States;United States National Institutes of Health;Vasodilation;western diet;Work

PROJECT_TITLE: The Role of Adaptor Protein Disabled-2 in Maintaining Endothelial Cell Function in Atherosclerosis

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


ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Narrative The recently discovered checkpoint inhibitors for cancer immunotherapy that target T cell activation through blockage of PD1/PDL1 or CTLA4 have had amazing success in a subset of cancers but poor success in other cancer types. Thus, additional targets for therapeutic intervention are needed that boost the immune response and, in particular, ones that target the innate immune system. The focus of this proposal is to understand how expression of ST8Sia6 accelerates tumor growth through modulation of the immune response through Siglec- E, and to determine if ST8Sia6 downregulation on tumors renders them more susceptible to immune attack.

PI_NAMEs: SHAPIRO, VIRGINIA SMITH (contact)

PROGRAM_OFFICER_NAME: HOWCROFT, THOMAS K

PROJECT_TERMS: Acceleration;Amaze;anti-PD-L1 therapy;Bone Marrow;cancer immunotherapy;cancer type;cell growth;Cell surface;Cells;Coculture Techniques;Colon Carcinoma;conditional knockout;CTLA4 gene;Databases;Development;Down-Regulation;Doxycycline;Engineering;Family;Frequencies;Glycolipids;glycosylation;Growth;Human;HuR protein;Immune;immune activation;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immune system;immunoregulation;Immunotherapy;Impairment;in vivo;in vivo Model;Innate Immune System;Knockout Mice;Ligands;lymph nodes;Macrophage;Maintenance;Malignant Neoplasms;MC38;Mediating;Membrane Glycoproteins;Microsatellite Instability;Modeling;Modification;mouse model;mRNA Stability;Mus;neoplastic cell;novel;overexpression;Patients;PD-1/PD-L1;Phenotype;Play;Pre-Clinical Model;Predisposition;programmed cell death ligand 1;programmed cell death protein 1;receptor;recruit;Regulation;response;RNA-Binding Proteins;Role;sialic acid binding Ig-like lectin;Sialic Acids;sialylation;Signal Pathway;success;synergism;T cell response;T-Cell Activation;T-Lymphocyte;targeted treatment;Testing;Tetanus Helper Peptide;Therapeutic Intervention;Transferase;Transgenes;Transplantation;tumor;Tumor Cell Line;tumor growth;Tumor Promotion;Tumor-associated macrophages;tumorigenic

PROJECT_TITLE: ST8Sia6 expression on tumors inhibits the immune response

STUDY_SECTION: TTT

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


NIH_SPENDING_CATS: Cancer;Lung;Lung Cancer;Nutrition

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: NARRATIVE  Mutant KRAS ( K M ) is the most common oncogenic mutation of lung cancer. We determined that in  lung cancer KM establishes a critical dependency on fatty acid synthase (FASN), the enzyme that  catalyzes the synthesis of saturated long chain fatty acids.  In this proposal, we will test the innovative hypothesis that FASN exerts a pro-survival function by providing fatty acids to feed the Lands cycle, the main cellular process that deflect ferroptosis, a form of programmed cell death. We anticipate that our findings will provide unanticipated insights into KM-driven tumorigenesis, unravelling novel therapeutic venues.

PI_NAMEs: SCAGLIONI, PIER PAOLO (contact)

PROGRAM_OFFICER_NAME: SALNIKOW, KONSTANTIN

PROJECT_TERMS: Acyl Coenzyme A;Acylation;Acyltransferase;Affect;airway epithelium;antitumor effect;Apoptosis;Biochemical Pathway;Bioenergetics;cancer cell;Cancer cell line;Cancer Etiology;cancer therapy;Cell Death;Cell Physiology;Cell Survival;Cells;Cessation of life;Coenzyme A;Coenzyme A Ligases;coping;Data;Dependence;Development;Drug Targeting;effective therapy;Enzymes;Essential Fatty Acids;Esters;experimental study;Extinction;Family member;fatty acid metabolism;Fatty Acids;Fatty-acid synthase;feeding;Goals;Growth;Guanosine Triphosphate Phosphohydrolases;Human;Image;Immunotherapy;In Vitro;in vivo;inhibitor;innovation;insight;Intracellular Accumulation of Lipids;Iron;Knowledge;Lead;Lecithin;lipid metabolism;Lipid Peroxides;lipidome;lipidomics;long chain fatty acid;lung cancer cell;lung tumorigenesis;Lysophosphatidylcholines;Maintenance;Malignant neoplasm of lung;Malignant Neoplasms;Metabolic;Metabolism;Minority;Modeling;mouse model;mutant;Mutation;Non-Small-Cell Lung Carcinoma;Nonesterified Fatty Acids;novel;novel therapeutics;Oncogenes;Oncogenic;Oral;Outcome;Oxidative Stress;Patients;peroxidation;Peroxides;Phase II Clinical Trials;Phenotype;Phospholipase A2;Phospholipids;PLA2G4C gene;Pre-Clinical Model;Process;Prognosis;Proliferating;Property;Proto-Oncogenes;Reaction;Reactive Oxygen Species;reconstitution;repaired;Resolution;Role;Signal Transduction;Specimen;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;tandem mass spectrometry;Testing;Therapeutic;therapeutic target;therapy resistant;Transgenic Mice;tumor;tumorigenesis;Validation

PROJECT_TITLE: Fatty acid metabolism regulates ferroptosis in mutant KRAS lung cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Contraception/Reproduction;Heart Disease;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: NARRATIVE  This research is relevant to public health because women who have had an adverse pregnancy outcome, such as hypertensive disorders of pregnancy, preterm delivery, or small for gestational age, are more likely to develop heart disease later in life. The objective of this research is to determine whether there are differences in ultrasound markers of heart and blood vessel disease risk in women who had an adverse pregnancy outcome compared with those who did not, and to determine whether blood pressure and proteins measured during a woman’s first pregnancy are linked to risk of heart and blood vessel disease. Our study is very relevant to the NHLBI’s mission to improve maternal cardiovascular health.

PI_NAMEs: KHAN, SADIYA SANA (contact)

PROGRAM_OFFICER_NAME: BURNS, KRISTIN

PROJECT_TERMS: Abnormal placentation;Accounting;Address;adjudication;Adverse event;adverse pregnancy outcome;Age;Ancillary Study;Angiogenesis Pathway;antiangiogenesis therapy;Biological Assay;Biological Markers;Blood Pressure;Blood Proteins;Blood Vessels;Cardiac health;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;Carotid Arteries;carotid intima-media thickness;Chronic;Clinical;cohort;cytokine;Data;Development;Disease;disorder risk;Early identification;early pregnancy;Enrollment;Ethnic Origin;experience;Exposure to;follow-up;Functional disorder;Funding;Future;Geography;Gestational Diabetes;Goals;Guide prevention;Guidelines;Heart;Heart Diseases;Heterogeneity;high risk;High Risk Woman;Hypertension;Image;improved;Incidence;Individual;Inflammation;Inflammatory;insight;Interleukin-6;Intervention;Life;Link;maternal morbidity;Maternal Mortality;Measures;Mediating;Mission;Monitor;Mothers;National Heart, Lung, and Blood Institute;new therapeutic target;novel;novel marker;novel therapeutics;Nulliparity;Outcome Study;Pathogenesis;Pathway interactions;Persons;Phenotype;Placentation;post pregnancy;Postpartum Period;Pregnancy;pregnancy disorder;Pregnancy Outcome;Premature Birth;prepregnancy;Prevention;Prevention strategy;Process;Proteomics;Public Health;Pulse Pressure;Race;recruit;Research;Research Priority;Risk;Risk Factors;risk prediction;Risk Reduction;Sampling;screening;Small for Gestational Age Infant;study population;Testing;Texture;ultrasound;United States;Validation;Vascular Diseases;Vascular Endothelial Growth Factor Receptor-1;Woman;Work;working group;young woman

PROJECT_TITLE: PRegnancy OuTcomEs and subclinical Cardiovascular disease sTudy: (PROTECT)

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: Nashville

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Narrative Faithful replication and maintenance of our genomes, which is vital to our survival, requires the action of complex multi-protein machinery that replicates our DNA and responds respond to aberrations in DNA that arise as a by-product of exposure to environmental toxins, sunlight, and even molecules produced naturally in cells. Defects in these protein machines lead to mutation and ultimately cancer and other diseases associated with genomic instabilities. Investigating the three-dimensional structure of the protein components of DNA replication and damage response machines and their interactions with each other and with the DNA will reveal intricate details of how replication and damage response occurs, what is defective in disease-associated mutant proteins, and open up new avenues for development of targeted therapies for patients suffering from maladies such as cancer that arise as a result of genomic instability.

PI_NAMEs: CHAZIN, WALTER J. (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Automobile Driving;Binding Proteins;Biochemical;biophysical properties;Biophysics;Cells;cofactor;Collaborations;Complex;Coupled;Cryoelectron Microscopy;daughter strand;Defect;Development;Disease;DNA;DNA Binding;DNA biosynthesis;DNA Damage;DNA polymerase alpha-primase;DNA Primase;DNA replication fork;Exposure to;Genome;Genomic Instability;Goals;insight;Knowledge;Lead;Length;Maintenance;Malignant Neoplasms;Modeling;Motor;Multiprotein Complexes;mutant;Mutation;Oxidation-Reduction;Pathway interactions;Patients;Play;Polymerase;Process;Property;Proteins;recruit;response;RNA chemical synthesis;Role;Signal Transduction;Single-Stranded DNA;structural biology;Structure;Sunlight;targeted treatment;Testing;three dimensional structure;Toxic Environmental Substances

PROJECT_TITLE: Integrative Structural Biology in DNA Replication and Damage Response


NIH_SPENDING_CATS: Diabetes;Genetics;Obesity

ORG_DEPT: PHYSIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: NARRATIVE Loss of mitochondria and oxidative capacity have been implicated in the development or progression of many diseases, from type 2 diabetes to cardiovascular diseases and skeletal muscle diseases. Understanding the mechanisms by which adipose cells respond to physiological signals, such as adrenergic stimulation, to build more mitochondria and higher capacity to oxidize nutrients, can present new ways for intervention in diseases associated with decreased oxidative capacity.

PI_NAMEs: KRALLI, ANASTASIA  (contact)

PROGRAM_OFFICER_NAME: GUPTA, DHANANJAY

PROJECT_TERMS: adipocyte biology;Adipocytes;Adipose tissue;Adrenergic Agents;Adrenergic Agonists;Biogenesis;Bioinformatics;Biology;Body Temperature;Brown Fat;Cardiovascular Diseases;Cell Physiology;Cell Respiration;cell type;Cells;Code;Coupled;Cytoplasm;Defect;Development;Disease;Environment;ERR1 protein;estrogen-related receptor;Family;Functional disorder;gain of function;Gene Expression;gene induction;Genes;Genetic Transcription;Genome;Goals;Grant;Health;Heart;Homeostasis;Human;insight;Insulin Resistance;insulin sensitivity;Intervention;Kidney;Lead;lifestyle intervention;Link;Lipids;Liver;loss of function;member;Messenger RNA;Metabolic;Metabolism;Mining;Mitochondria;Mitochondrial Proteins;Molecular;mouse model;Mus;Myopathy;Nature;Non-Insulin-Dependent Diabetes Mellitus;Norepinephrine;novel;Nuclear;Nuclear Orphan Receptor;Nuclear Receptors;Nutrient;Obesity;Obesity associated disease;Organelles;overexpression;oxidation;Oxidative Phosphorylation;Pathway interactions;Pattern;Peroxisome Proliferator-Activated Receptors;pharmacologic;physiologic stressor;Physiological;Physiology;Post-Transcriptional Regulation;posttranscriptional;Proteins;Publishing;receptor;Receptor Signaling;recruit;Regulation;Regulator Genes;Regulatory Element;response;Role;Signal Transduction;Skeletal Muscle;Tertiary Protein Structure;Testing;Therapeutic Intervention;Thermogenesis;Tissues;trait;transcription factor;Transcriptional Regulation;Work

PROJECT_TITLE: Regulators of adipocyte oxidative metabolism

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Despite enormous progress, significant challenges remain in preventing, treating and curing HIV infection. The Boston/Jackson/Providence HIV Clinical Trials Unit will carry out innovative clinical trials that address major questions in HIV clinical research. The results of these studies will lead to major improvements in ways to prevent and treat HIV and related diseases.

PI_NAMEs: BADEN, LINDSEY ROBERT;KURITZKES, DANIEL R. (contact);MAYER, KENNETH H

PROGRAM_OFFICER_NAME: ROBY, GREGG A,

PROJECT_TERMS: Address;Adjuvant;Administrative Efficiency;Affect;African American population;AIDS clinical trial group;AIDS diagnosis;AIDS prevention;Anti-Retroviral Agents;Antigens;Area;Behavioral;Boston;candidate selection;Chemoprophylaxis;Cities;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Design;Clinical Trials Network;Clinical Trials Unit;co-infection;Collaborations;Combined Vaccines;Communities;community engagement;Conduct Clinical Trials;Data;Decision Making;design;Development;Disease;Disease remission;Epidemiology;Evaluation;experience;Formulation;Funding;General Hospitals;Goals;Health;Hepatitis B Virus;HIV;HIV Infections;HIV prevention trials network;HIV vaccine;HIV Vaccine Trials Network;HIV-1;HIV/AIDS;Hospitals;Human immunodeficiency virus test;improved;Infection;Infrastructure;innovation;Institution;Intervention;Israel;Laboratory Research;Leadership;Licensing;Massachusetts;Medical center;medical schools;Methods;metropolitan;Mississippi;Modality;Names;National Institute of Allergy and Infectious Disease;neutralizing antibody;novel;Occupational activity of managing finances;Organ;organizational structure;Pharmacy facility;Phase;phase 1 study;phase 2 testing;phase I trial;Population;Pregnancy;prevent;Prevention;Prevention Research;Prevention strategy;Preventive vaccine;Research;Research Personnel;Research Priority;Resource Allocation;Resources;response;Rhode Island;social;Social Behavior;Southeastern United States;STI prevention;Structure;System;Technology;Testing;Therapeutic;Therapeutic Studies;treatment research;Universities;vaccine candidate;Vaccine Research;Vaccine Therapy;vaccine trial;Vaccines;virology;Woman;Work

PROJECT_TITLE: Boston HIV CTU


NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Lung;Lung Cancer;Precision Medicine;Radiation Oncology

ORG_CITY: SEATTLE

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE Patients with metastatic non-small cell lung cancer undergo complex combinations of treatments including chemotherapy, immunotherapy, and radiation therapy; and while some patients have prolonged cancer control from therapy, others develop rapid progression. We propose to assess and monitor treatment response with positron emission tomography imaging and circulating immunologic biomarkers to improve patient outcomes by quickly detecting patients who are not benefiting from standard of care chemo-immunotherapy, and selecting for patients whose outcomes can be improved with the addition of radiation therapy. Development and validation of combined imaging and circulating biomarkers can support treatments that are adapted to the response of individual patients with metastatic non-small cell lung cancer and improve clinical outcomes.

PI_NAMEs: BOWEN, STEPHEN R. (contact);ZENG, JING

PROGRAM_OFFICER_NAME: VIKRAM, BHADRASAIN

PROJECT_TERMS: anti-PD-1;Biological Assay;Biological Markers;biomarker identification;biomarker signature;burden of illness;Cancer Control;cancer survival;CD8-Positive T-Lymphocytes;Cells;Cessation of life;chemotherapy;circulating biomarkers;Clinical;clinical imaging;Clinical Trials;Combination Drug Therapy;Combined Modality Therapy;Complex;Consensus;cytokine;Data;Development;Disease;disorder control;Early Intervention;Enrollment;External Beam Radiation Therapy;Financial Hardship;fluorodeoxyglucose positron emission tomography;Future;Glycolysis;high risk;Image;imaging biomarker;Immune;Immune checkpoint inhibitor;Immune response;Immuno-Chemotherapy;Immunologic Markers;Immunophenotyping;Immunotherapy;improved;improved outcome;individual patient;individual response;Intervention;irradiation;learning strategy;Lesion;Ligands;Link;Malignant neoplasm of lung;Metabolic;Monitor;monocyte;multidisciplinary;Newly Diagnosed;Non-Small-Cell Lung Carcinoma;Observational Study;Outcome;outcome prediction;Patient Selection;patient stratification;Patient-Focused Outcomes;Patients;Pattern;Peripheral;peripheral blood;phase II trial;Phenotype;Positron-Emission Tomography;Precision Medicine Initiative;Precision therapeutics;predictive marker;prognostic value;prognostication;programmed cell death ligand 1;Progression-Free Survivals;Progressive Disease;prospective;Proteins;quantitative imaging;Radiation;radiation response;Radiation therapy;Radio;radiomics;randomized trial;response;response biomarker;Risk;risk stratification;Site;standard of care;Standardization;support tools;survival outcome;synergism;Systemic disease;Systemic Therapy;T-Cell Receptor;Therapeutic;Toxic effect;Treatment Efficacy;treatment response;Treatment-related toxicity;tumor;Tumor Volume;United States National Institutes of Health;uptake;Validation;X-Ray Computed Tomography

PROJECT_TITLE: Biomarkers of Response to Immuno-chemotherapy & oliGometastatic Hypofractionated radioTherapy (BRIGHT) for Lung Cancer: Synergy of PET/CT Imaging and Peripheral Blood Assays

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Neurofibromatosis;Neurosciences;Pediatric;Precision Medicine;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Impact This project employs novel Nf1 mouse strains, human iPSC lines, and converging experimental methodologies to define the risk factors and etiologies that dictate the development, clinical course, and treatment response of neurological dysfunction in children with NF1 with translatability to future precision medicine strategies.

PI_NAMEs: GUTMANN, DAVID H (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Affect;Assessment tool;base;Bioinformatics;Brain Neoplasms;Caring;Cell Line;Child;Clinical;clinical application;clinical subtypes;Cognitive;Development;Diagnosis;disease heterogeneity;Disease Outcome;disorder risk;effective therapy;Engineering;epidemiology study;Etiology;Future;Gene Mutation;Genetic;Genetically Engineered Mouse;Germ Lines;Germ-Line Mutation;Goals;Heterogeneity;Human;human induced pluripotent stem cells;Individual;Infant;Medical;Medicine;Methodology;Mission;Modeling;Molecular;Mouse Strains;Mus;Nervous System Disorder;Neurofibromatosis 1;neurogenetics;Neurologic;Neurologic Dysfunctions;Neurology;NF1 gene;novel;patient derived induced pluripotent stem cells;Patients;precision medicine;Problem behavior;prognostic;Research Personnel;Risk Assessment;Risk Factors;System;Systems Biology;Translating;treatment response

PROJECT_TITLE: Defining the Mechanistic Basis for Neurofibromatosis-1 Nervous System Disease Heterogeneity


NIH_SPENDING_CATS: Genetics;HIV/AIDS;Human Genome;Immunization;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Program Narrative Despite the critical role for memory B cells in establishing long-lived humoral immunity, the molecular programs that regulate their enhanced function and protective capabilities remain to be defined. Herein, we propose that epigenetic mechanisms serve as a molecular memory of prior states and underpins the enhanced recall responses of memory B cells. Using a robust set of assays and tools, we will define the epigenetic architecture of memory B cell subsets and identify pathways and transcription factors that ultimately could be used to improve immunity or treat autoimmune diseases where memory B cells are a component.

PI_NAMEs: SCHARER, CHRISTOPHER D (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Antigens;Architecture;ATAC-seq;Autoimmune Diseases;B-Cell Activation;B-Lymphocyte Subsets;B-Lymphocytes;Binding Sites;Bioinformatics;bioinformatics pipeline;Biological Assay;Cell division;Cell Physiology;Cells;Cellular Assay;Chromatin;Chromatin Structure;Cleavage Under Targets and Release Using Nuclease;Data;Deposition;design;differentiation protocol;Disease;DNA;DNA Methylation;Enhancers;Enzymes;Epigenetic Process;epigenetic profiling;Equilibrium;EZH2 gene;Gene Expression;Gene Expression Profiling;gene network;Generations;Genetic;genetic signature;Genetic Transcription;Goals;Heritability;Histone H3;histone modification;Homeostasis;Humoral Immunities;Immune response;Immunity;Immunoglobulin A;Immunoglobulin Class Switching;Immunoglobulin G;Immunoglobulin M;Immunologic Memory;Immunotherapeutic agent;improved;in vivo;Influenza;influenza infection;Instruction;Lupus;Lysine;Maps;Mediating;Memory;Memory B-Lymphocyte;Metabolic;Metabolism;Methylation;Molecular;Mouse Strains;Mus;Nature;Outcome;Pathway interactions;Patients;Phenotype;plasma cell differentiation;Plasma Cells;Population;Process;programs;promoter;Property;Protocols documentation;Reaction;Regulatory Element;Repression;response;Role;Series;shared memory;Stimulus;Structure of germinal center of lymph node;T-Lymphocyte;Tamoxifen;targeted treatment;therapeutic target;therapy development;tool;transcription factor;transcriptome;transcriptome sequencing;Vaccine Design;vaccine strategy;Work

PROJECT_TITLE: Epigenetic instruction of memory B cell function and reactivation

STUDY_SECTION: CMIB

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


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Genetics;Human Genome;Nutrition;Obesity;Patient Safety;Precision Medicine;Prevention

PHR: There is considerable variation in response to the same antidiabetic therapy among individual diabetic patients. The proposed study aims to identify biomarkers to predict how an individual diabetic patient will respond to the glucagon-like peptide-1 receptor (GLP1R) agonist class of antidiabetic drugs. Availability of predictive biomarkers would enable physicians to prescribe therapies for each individual patient based on predictors of the magnitude of beneficial response.

PI_NAMEs: BEITELSHEES, AMBER L (contact);TAYLOR, SIMEON I.

PROGRAM_OFFICER_NAME: LI, YAN

PROJECT_TERMS: Acceleration;Aftercare;Agonist;American;Amish;Amputation;Anti-diabetic Drugs;Biological Markers;biomarker identification;Blindness;Body Weight decreased;Bolus Infusion;Cardiovascular system;Circulation;Clinical;clinical predictors;Clinical Trials;clopidogrel;cost;County;Data;density;design;Diabetes Mellitus;Diabetic Angiopathies;diabetic patient;Diet;DNA Sequence;Dose;Drug Prescriptions;End stage renal failure;Environmental Risk Factor;European;Evaluation;Event;Exercise;experience;Frequencies;General Population;Genetic;Genetic Anticipation;Genetic Markers;Genetic study;genetic variant;genome wide association study;Genotype;GLP-I receptor;Glucose;glucose metabolism;glycemic control;Glycosylated hemoglobin A;Head;healthy volunteer;improved;Individual;individual patient;individual response;insulin secretion;intravenous administration;intravenous glucose tolerance test;liraglutide;Literature;logarithm;Measurement;Measures;Mediating;Mediation;National Heart, Lung, and Blood Institute;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Obesity;optimal treatments;Outcome;Overweight;Participant;patient population;patient response;Patients;Pharmaceutical Preparations;Pharmacodynamics;Pharmacogenetics;Pharmacogenomics;pharmacologic;Phase;Physicians;Physiological;Plasma;Population;precision medicine;predictive marker;primary endpoint;Principal Investigator;programs;Property;Publishing;recruit;Reporting;Research;Research Subjects;response;Risk;Sampling;side effect;subcutaneous;Trans-Omics for Precision Medicine;Type 2 diabetic;Variant;volunteer;whole genome

PROJECT_TITLE: Pharmacogenetics of the Response to a GLP1R Agonist

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Cannabinoid Research;Chronic Pain;Complementary and Integrative Health;Dietary Supplements;Endocannabinoid System Research;Natural Products;Neurodegenerative;Neurosciences;Opioids;Pain Research;Peripheral Neuropathy;Therapeutic Cannabinoid Research

ORG_CITY: HONOLULU

ORG_NAME: QUEEN'S MEDICAL CENTER

ORG_STATE: HI

PHR: PROJECT NARRATIVE Chronic pain – often arising from musculoskeletal injury, neurological disease, cancer, or autoimmune disease – affects ~100 million Americans. There is growing evidence that the plant Cannabis sativa has analgesic and anti‐inflammatory properties without the detrimental side effects seen by opioid use. Our studies will find the ingredients in Cannabis that reduce inflammation and chronic pain, which may help abate the nation's opioid epidemic.

PI_NAMEs: MACKIE, KENNETH ;PENNER, REINHOLD  (contact)

PROGRAM_OFFICER_NAME: BELFER, INNA

PROJECT_TERMS: Abate;absorption;Acceleration;Acute;Address;Affect;Agonist;American;Analgesics;Animal Model;animal pain;Anti Inflammatory Analgesics;Anti-Inflammatory Agents;aqueous;Autoimmune Diseases;Binding Proteins;Biochemical;Biological;Biological Assay;Biology;Biophysics;Calcium Signaling;Cannabinoids;Cannabis;Cannabis sativa plant;Cell Line;Cells;Cellular Assay;cellular imaging;Cessation of life;Chronic;chronic pain;CNR1 gene;CNR2 gene;combinatorial;cytokine;Data;Drug Kinetics;economic cost;efficacy evaluation;Electrophysiology (science);Endocannabinoids;Evaluation;Excretory function;experimental study;Flavonoids;Freund's Adjuvant;G-Protein-Coupled Receptors;Genetic;GPR55 receptor;GTP-Binding Proteins;high throughput screening;Human;human model;Immune;Immunoassay;In Vitro;in vivo;in vivo Model;Individual;Inflammation;Inflammation Mediators;Inflammatory;inflammatory pain;inhibitor;Ion Channel;knowledge base;Lignans;Link;Macrophage;Maintenance;Malignant Neoplasms;mast cell;Measures;Mediating;Membrane Potentials;Metabolism;Microglia;Microsomes;Molecular;Molecular Target;monocyte;mouse model;musculoskeletal injury;Natural Products Chemistry;Nature;Nervous System Disorder;Neurologic Dysfunctions;Neuropathy;neutrophil;Nociception;Opioid Analgesics;opioid epidemic;opioid overdose;opioid use;Paclitaxel;Pain;pain model;painful neuropathy;patch clamp;Pathway interactions;pharmacologic;Pharmacology;Phytochemical;Plants;Plasma Proteins;Potassium Channel;Property;Public Health;receptor;Research;screening;side effect;Signal Pathway;Signal Transduction;Small Interfering RNA;Solubility;sulfated glycoprotein 2;System;T-Lymphocyte;Terpenes;Therapeutic;TRP channel;TRPV1 gene;Western Blotting;Work

PROJECT_TITLE: Modulation of pain mechanisms by cannabis-derived phytochemicals.


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Hearing Loss;Neurosciences

ORG_CITY: SAN DIEGO

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: SAN DIEGO STATE UNIVERSITY

PHR: Public Health Relevance This research will benefit individuals who are deaf and use sign language as their primary language and will support the medical and rehabilitative organizations that serve this population. The findings will advance knowledge of the neural underpinnings of sign language, providing crucial information to clinicians and neurologists who are treating deaf patients with brain injury or disease.

PI_NAMEs: EMMOREY, KAREN  (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Adopted;Agreement;American Sign Language;Area;Body part;Brain;Brain Diseases;Brain Injuries;Child;Cognition;cognitive neuroscience;Communication;cortex mapping;Coupled;deaf;density;design;Diagnosis;Electrophysiology (science);Event-Related Potentials;Exhibits;experience;experimental study;extrastriate;extrastriate visual cortex;Foundations;Functional Magnetic Resonance Imaging;Gestures;Goals;Hearing;Human;indexing;Individual;Inferior;Inferior frontal gyrus;Injury;insight;Investigation;Knowledge;Language;language comprehension;Language Development;Language Disorders;language impairment;language perception;language processing;Learning;Left;lexical;Linguistics;Location;Maintenance;Manuals;Maps;Medical;Methods;Modality;Modeling;Motor;Multimodal Imaging;National Institute on Deafness and Other Communication Disorders;Neighborhoods;neural;neural circuit;neural correlate;neural network;Neurobiology;Neurologist;Neurons;neurophysiology;Parents;Parietal Lobe;Patients;pedagogy;Perception;Personal Satisfaction;Persons;phonology;Population;practical application;Process;Property;Psychology;public health relevance;Recycling;Rehabilitation therapy;Research;response;Role;Semantics;Sensory;Shapes;Sign Language;sound;Speech;Speech Perception;Stimulus;Strategic Planning;Structure;Structure of superior temporal sulcus;Structure of supramarginal gyrus;support network;syntax;System;Testing;theories;United States;Visual;Visuospatial

PROJECT_TITLE: Language, Modality and the Brain

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


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

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE There is a great clinical need for additional therapies for refractory Inflammatory Bowel Disease (IBD). In this proposal, we will study intestinal epithelial cells in mouse models and directly from patients to uncover more about the pathways involved in preserving intestinal epithelial integrity. The goal of this proposal is to identify potential methods of protecting intestinal epithelial cells from injury, rather than further suppressing the immune system, in patients with IBD.

PI_NAMEs: KATTAH, MICHAEL GEORGE (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Acute;Adult;Affect;Antibodies;Bioinformatics;Biology;career;career development;CASP8 gene;Caspase Inhibitor;Cell Death;Cell Death Induction;cell injury;Cell secretion;Cell Survival;Cells;Cellular biology;Cessation of life;Clinical;Clinical Trials;Coculture Techniques;colon cancer risk;Complement;CRISPR/Cas technology;Crohn's disease;Cytoprotection;Data;Development Plans;disability;Disease;Epithelial Cells;epithelial injury;Epithelium;Exhibits;experience;Feedback;Frequencies;gene product;Genes;Genetic;genome wide association study;Goals;Goblet Cells;gut inflammation;Health;Health Expenditures;Hematopoietic;Hemorrhage;Histologic;Homeostasis;Hospitalization;Human;Immune;Immune system;Immunology;Immunosuppression;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Injury;interest;intestinal epithelium;intestinal homeostasis;intestinal injury;Intestines;kinase inhibitor;Lead;Link;Methods;Microscopy;Modeling;Morbidity - disease rate;mortality;mouse model;Mucous Membrane;Mus;neutralizing antibody;Operative Surgical Procedures;Organoids;overexpression;Paneth Cells;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Personal Satisfaction;Pharmaceutical Preparations;Phosphorylation;Play;Predisposition;preservation;prevent;Publishing;Refractory;Research;Research Personnel;RIPK1 gene;risk variant;RNA;Role;Sampling;Signal Transduction;Signaling Protein;single-cell RNA sequencing;skills;small molecule;stem cell differentiation;Stimulus;Stromal Cells;System;targeted treatment;Techniques;Testing;TNF gene;Training;Ulcerative Colitis;Viral;Work

PROJECT_TITLE: Mechanisms of intestinal epithelial injury in intestinal inflammation


NIH_SPENDING_CATS: Aging;Atherosclerosis;Autoimmune Disease;Cardiovascular;Diabetes;Digestive Diseases;Heart Disease;Liver Disease;Pediatric;Prevention

PHR: Intensive insulin therapy, which requires meticulous insulin dosing, every day and through the night, reduces cardiovascular disease in type 1 diabetes but is difficult for patients to maintain. We expect that the proposed study will lead to new drugs that can supplement insulin therapy and prevent atherosclerosis even when intensive insulin therapy is not possible.

PI_NAMEs: BIDDINGER, SUDHA B (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: absorption;Acute;Adrenergic Agonists;atheroprotective;Atherosclerosis;bile acid metabolism;Bile Acids;bile salts;Cardiovascular Diseases;cardiovascular disorder risk;Cholesterol;cholesterol absorption;Compensation;Data;Defect;Dependovirus;Diabetes Mellitus;Diabetic mouse;diabetic patient;Dietary Cholesterol;Dose;drug development;gain of function;Genes;Glucose;Glucose Clamp;Goals;Hepatic;Hepatocyte;high risk;Homeostasis;Human;hypercholesterolemia;Hyperglycemia;Hyperinsulinism;Hyperlipidemia;Impairment;Individual;Inflammation;Inflammatory;insight;Insulin;Insulin deficiency;Insulin Receptor;insulin regulation;insulin signaling;Insulin-Dependent Diabetes Mellitus;Intestines;Knock-out;LDL Cholesterol Lipoproteins;lipid metabolism;Lipids;Liver;loss of function;Measures;Micro Array Data;Modeling;mouse model;Mus;novel;novel drug class;novel therapeutics;oxysterol 7-alpha-hydroxylase;Pathogenesis;Patients;Peripheral;Pharmaceutical Preparations;Physiological;Plasma;Play;Portal vein structure;prevent;Regulation;restoration;Risk Factors;Role;Signal Induction;Signal Pathway;Site;Streptozocin;subcutaneous;Testing;type I diabetic;Validation;vascular inflammation

PROJECT_TITLE: Novel Targets for Reducing Atherosclerosis in Type 1 Diabetes

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

PHR: Narrative The ultimate goal of this project is to engineer antibodies that we have previously identified that have broad and potent activity against most HIV viruses into ones that are active against all HIV viruses. After engineering the antibodies, we will test in a mouse model in the hope that these antibodies can eventually be used to prevent or treat HIV infection in humans.

PI_NAMEs: SAJADI, MOHAMMAD MOHSENI (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, GERARD

PROJECT_TERMS: Adherence;AIDS prevention;Animal Model;Anti-Retroviral Agents;Anti-viral Agents;Antibodies;Antibody Binding Sites;antibody engineering;Autologous;Behavior;Binding;Binding Sites;Biochemical;biophysical properties;Cells;clinically relevant;Collection;combinatorial;Crystallography;Data;design;Development;Drug Combinations;Drug Kinetics;Engineering;Ensure;Exhibits;experimental study;Face;Family;Germ Lines;Goals;Half-Life;HIV;HIV envelope protein;HIV Envelope Protein gp120;HIV Infections;HIV-1;HIV/AIDS;Human;human monoclonal antibodies;humanized mouse;IgG1;Immune;immunogenic;immunotherapy trials;improved;In Vitro;in vivo;Infection;interest;Libraries;Life Extension;Logistics;Mediating;Membrane Proteins;Methods;Modality;Molecular Sieve Chromatography;Monoclonal Antibodies;mouse model;Mutagenesis;Neutralization Tests;neutralizing antibody;novel;Passive Immunization;Passive Immunotherapy;Persons;Pharmaceutical Preparations;Plasma;Polysaccharides;pre-exposure prophylaxis;prediction algorithm;prevent;Prevention;Preventive;Property;prophylactic;protective efficacy;Recombinants;recruit;Resistance;Risk;side effect;Solubility;Structure;Surface;Target Populations;Techniques;Testing;Vaccines;Variant;Virus;Work;X-Ray Crystallography;Yeasts

PROJECT_TITLE: Engineering of pan-neutralizing anti-HIV envelope antibodies

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Neurosciences

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Relevance: Because this basic science proposal relates how different parts of the auditory cortex participate in sound perception, the work is relevant to increasing the understanding about how restricted brain damage such as that caused by stroke affects auditory function. The results of these studies will help us better understand how attention modulates auditory activity and thus has relevance for the spectrum disorders (that include, but are not limited to attention deficit disorder, dyslexia, etc). The results also could have relevance in helping to guide approaches to coding for hearing aids and cochlear implants since both neural coding and the ability to attend sounds are relevant for designing these devices.

PI_NAMEs: SUTTER, MITCHELL L (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TITLE: Spectral and Temporal Integration in the Auditory System


NIH_SPENDING_CATS: Nutrition;Obesity

ORG_CITY: NEW YORK

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: World-wide obesity rates pose a significant threat to public health, however pathways promoting weight loss are poorly understood. During lipolysis, adipocytes reuptake and oxidize a significant proportion of the released fatty acids. I propose to investigate a novel function of STAT3, required for this energy expending process, which occurs in non-thermogenic white adipocytes and therefore could be a powerful therapeutic target for achieving weight loss and winning the battle against obesity.

PI_NAMEs: REILLY, SHANNON MARIE (contact)

PROJECT_TERMS: absorption;Acyltransferase;Adipocytes;Adipose tissue;Adrenergic Agents;Adrenergic Receptor;Agonist;alpha-glycerophosphoric acid;Animals;Binding;Biological;Biological Assay;Body Weight decreased;Catecholamines;Cell Respiration;Cells;Co-Immunoprecipitations;Cyclic AMP;Data;Defect;Dependence;design;Development;diet-induced obesity;energy balance;Energy Metabolism;Esterification;Esterified Fatty Acids;Event;Exhibits;experimental study;Fasting;fatty acid metabolism;fatty acid oxidation;Fatty Acids;feeding;Female;Glycerol;High Fat Diet;Homeostasis;Hypertriglyceridemia;improved;In Vitro;in vivo;insight;Intake;Knockout Mice;Link;Lipids;Lipolysis;male;MAPK8 gene;Maps;Metabolic;Metabolic Diseases;Modeling;Mus;mutant;Mutant Strains Mice;Nature;Nerve;non-genomic;Nonesterified Fatty Acids;novel;novel therapeutic intervention;Nutrient;Obesity;obesity development;oxidation;Pathway interactions;Phosphorylation;Phosphorylation Site;Phosphotransferases;Physiological;Post-Translational Protein Processing;preference;Process;Protein Isoforms;Proteins;Proteomics;Public Health;recruit;Regulation;Regulatory Pathway;response;reuptake;Role;Signal Pathway;Signal Transduction;STAT1 protein;Stat2 protein;Stat3 protein;Sympathetic Nervous System;Techniques;therapeutic target;Time;Triglycerides;Weight Gain

PROJECT_TITLE: Regulation of fatty acid metabolism in adipocytes

STUDY_SECTION: MCE

STUDY_SECTION_NAME: Molecular and Cellular Endocrinology Study Section[MCE]


NIH_SPENDING_CATS: Diabetes;Nutrition;Obesity

PHR: Project Narrative: The proposed studies will advance our understanding of a basic mechanism by which adipose tissue FA oxidation is regulated, and how its dysregulation impacts energy metabolism in obesity. The data derived from this project will guide the design of new therapeutic approaches that improve outcomes for patients with obesity and its related metabolic disorders such insulin resistance and type 2 diabetes.

PI_NAMEs: LIU, JUN  (contact)

PROJECT_TERMS: Ablation;Acute;adipocyte differentiation;Adipocytes;Adipose tissue;Adult;Affect;Agonist;Apolipoproteins;attenuation;Binding;Body fat;Body Temperature;Body Weight;Body Weight decreased;Brown Fat;Carbon;Cell Line;Cell model;cell type;Cells;Chronic;combat;Data;design;Development;diet-induced obesity;dietary;energy balance;Energy Metabolism;enzyme activity;Enzymes;Epidemic;Exhibits;Family;fat burning;Fatty acid glycerol esters;fatty acid oxidation;Fatty Acids;gain of function;Glucose;glucose metabolism;glucose tolerance;Goals;Guanosine Triphosphate Phosphohydrolases;Housing;Human;improved outcome;In Vitro;in vivo;inhibitor;insight;Insulin Resistance;insulin sensitivity;Knock-out;Knockout Mice;lipid metabolism;loss of function;Mammals;Mass Spectrum Analysis;Measures;member;Metabolic;Metabolic Diseases;Metabolic syndrome;Mitochondria;Modeling;Molecular;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;Normal tissue morphology;novel;novel therapeutic intervention;obese patients;Obesity;Organ;oxidation;Oxygen Consumption;Pathogenesis;Phenotype;Physiological;Play;Prevalence;Proteins;recruit;Regulation;Respiration;Rodent;Role;Stable Isotope Labeling;subcutaneous;Temperature;Testing;Thermogenesis;Tissues;transgene expression;Transgenic Mice;Transgenic Organisms

PROJECT_TITLE: Lipid metabolism and adipose tissue function

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


PHR: PROJECT NARRATIVE Ucp1-dependent thermogenesis in brown adipocytes has been traditionally viewed as a major thermogenic mechanism for systemic thermoregulation and energy balance. This proposal investigates how brown adipocytes regulates energy homeostasis independently of Ucp1.

PI_NAMEs: WANG, BIAO  (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Abbreviations;Ablation;Acids;Acute;Adipocytes;Adipose tissue;Aging;beta-adrenergic receptor;Brown Fat;Cell Nucleus;Cells;cold stress;complex IV;conditional knockout;cytochrome c oxidase;Defect;Diet;Dietary Proteins;differentiation in vitro;Diphtheria Toxin;energy balance;Energy Metabolism;Etiology;Exhibits;Family;feeding;Future;Genetic;Health;High Fat Diet;Homeostasis;Human;improved;in vivo;Investigation;Knock-out;Knockout Mice;Leigh Disease;Leucine;Lipids;Mass Spectrum Analysis;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;metabolic fitness;Metabolism;Mitochondria;Mitochondrial DNA;Molecular;mouse model;Mus;Mutation;novel;novel therapeutic intervention;obesity treatment;overexpression;Physiologic Thermoregulation;Physiological;Process;programs;Protein-Restricted Diet;Proteins;Proteome;Receptor Signaling;Regulation;Respiration;response;RNA;Role;Side;Stress Tests;Temperature;Therapeutic;Thermogenesis;uncoupling protein 1;uptake;Variant;Visualization;Work

PROJECT_TITLE: Ucp1-independent functions in brown and beige adipocytes


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Health Services;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Pediatric;Prevention;Primary Health Care;Telehealth

ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

PHR: NARRATIVE Mental illnesses often first appear in childhood and yet go mostly untreated until a serious disorder develops. This study will (a) implement ways to identify early mental health needs in children 4-12 years of age using free text notes entered into medical records, and (b) carry out a two-arm randomized trial to test if offering navigator support and video-based psychotherapy result in more mental health visits over a 6-month period of time.

PI_NAMEs: PENFOLD, ROBERT B. (contact)

PROGRAM_OFFICER_NAME: MARRO, MARY ACRI

PROJECT_TERMS: 12 year old;Abnormal coordination;Accident and Emergency department;Address;adjudication;Adolescent;Adult;Antipsychotic Agents;Appointment;arm;burden of illness;California;Caring;Case Manager;Child;child mental health service;Childhood;Chronic;Clinic;Clinical;Communities;comparison control;comparison intervention;Consent;Data;Diagnosis;Disease;Documentation;Dose;Early identification;Eligibility Determination;Enrollment;Family;Family health status;follow-up;Goals;Health Personnel;Health Services Accessibility;Health system;Healthcare Systems;Home;improved;improved outcome;Individual;Integrated Health Care Systems;Intervention;Intervention Studies;Licensing;Logistic Regressions;Machine Learning;machine learning algorithm;Managed Care;Medical Records;medical specialties;Mental Depression;Mental disorders;Mental Health;mental health organization;Mental Health Services;Modeling;Monitor;motivational enhancement therapy;Natural Language Processing;Nurses;Outcome;outreach;participant enrollment;Patients;peer;Persons;Pharmaceutical Preparations;pragmatic randomized trial;pragmatic trial;prediction algorithm;predictive modeling;prevent;Primary Care;primary care provider;primary outcome;Process;Professional counselor;programs;Provider;Psyche structure;Psychotherapy;random forest;randomized trial;recruit;Registries;Reporting;Research;Role;Schedule;screening;secondary outcome;severe mental illness;skills;social stigma;Social Workers;structured data;Symptoms;Testing;Text;Therapeutic;Time;time use;tool;treatment arm;treatment as usual;trial design;urgent care;usual care arm;video visit;Videoconferencing;Visit;waiver;Washington;Work;Youth

PROJECT_TITLE: Assisted Identification and Navigation of Early Mental Health Symptoms in Children

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Immunization;Immunotherapy;Women's Health Research

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The triple negative breast cancer (TNBC), which is characterized by rapid growth, metastasis and recurrence, comprises about 15% of all breast cancers, and often regrows after primary treatment, leading to poor prognosis in TNBC patients. It is highly desired to develop an effective therapy for elimination of TNBC. Therefore, the combined antibody-drug conjugates (ADCs) that integrate the advantages of specific targeting and antibody- dependent cellular cytotoxicity of a novel tumor-specific monoclonal antibody and the direct cytotoxicity of the antibody-delivered payloads will be developed and characterized for TNBC treatment.

PI_NAMEs: LIU, RUNHUA RUNA (contact);LIU, XIAOGUANG MARGARET

PROGRAM_OFFICER_NAME: BOURCIER, KATARZYNA

PROJECT_TERMS: 4T1;Animal Model;anti-cancer;Anti-CD47;Antibodies;antibody-dependent cell cytotoxicity;Antibody-drug conjugates;Antigens;Biodistribution;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Patient;Breast Cancer Treatment;cancer subtypes;CD276 gene;CD47 gene;Cell Death;Cell surface;Cells;chemotherapy;chimeric antigen receptor;Clinical;Clinical Trials;curative treatments;cytotoxic;Cytotoxic Chemotherapy;cytotoxicity;design;dosage;Dose;Doxorubicin;Drug Kinetics;Drug resistance;Drug Synergism;effective therapy;engineered T cells;Epidermal Growth Factor Receptor;Evaluation;Experimental Designs;Extracellular Domain;folate-binding protein;Future;gemcitabine;glycosylation;Goals;Human;Imaging Techniques;immune activation;Immune response;improved;In Vitro;in vivo;in vivo imaging system;inhibitor;innovation;Investigation;Laser Scanning Confocal Microscopy;Luciferases;Malignant Breast Neoplasm;Malignant Neoplasms;Maximum Tolerated Dose;MDA MB 231;MDA-MB-468;Mediating;Medical;microscopic imaging;Modeling;Monoclonal Antibodies;Mus;Neoplasm Metastasis;neoplastic cell;Normal Cell;novel;Operative Surgical Procedures;overexpression;Paclitaxel;Patients;Pharmaceutical Preparations;Positron-Emission Tomography;pre-clinical;Pre-Clinical Model;preclinical evaluation;prevent;Procedures;Production;Prognosis;Protocols documentation;Quality of life;rapid growth;receptor;Recurrence;Recurrent tumor;Relapse;Residual state;response;Safety;Sampling;side effect;small molecule;small molecule inhibitor;Solid Neoplasm;Specificity;Surface;Survival Rate;synergism;systemic toxicity;targeted treatment;Testing;Therapeutic;Toxic effect;translational applications;translational potential;treatment strategy;triple-negative invasive breast carcinoma;tumor;Tumor Angiogenesis;Tumor Suppression;tumor xenograft;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Synergistic Targeted Therapy of Antibody-Drug Conjugates for Triple-Negative Breast Cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

PHR: NARRATIVE Gene translocations often create fusion oncoproteins (FOs) that cause uncontrolled cell proliferation and oncogenesis in a wide variety of cancers. Our preliminary results show that gene fusions often create FOs that are abnormal transcription factors that we hypothesize drive oncogenesis by forming aberrant transcription centers, and other aberrant functional bodies through the process of liquid-liquid phase separation (LLPS). Our studies are addressing open questions regarding the oncogenic mechanisms associated with myriad FOs and may enable mechanistic interpretation of clinical genomics data on novel fusion oncogenes in the future.

PI_NAMEs: DENIZ, ASHOK A;KRIWACKI, RICHARD W (contact);MOHAN, MADAN

PROGRAM_OFFICER_NAME: AMIN, ANOWARUL

PROJECT_TERMS: Address;Algorithms;Amino Acid Sequence;Binding;Biological Process;Biophysics;Cell Nucleus;Cell Proliferation;cell transformation;Cells;Childhood Leukemia;Chromatin;Clinical;Code;Computer Analysis;Data;Disease;Distal;DNA;Elements;Enhancers;EWS-FLI1 fusion protein;Fusion Oncogene Proteins;Future;Gene Abnormality;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Gene Fusion;gene translocation;Genes;Genetic Transcription;genomic data;Genomic Segment;Hematopoietic;Homeobox Genes;HOXA9 gene;Hybrids;In Vitro;Information Resources;lens;Link;Liquid substance;Malignant Neoplasms;Mediating;Membrane;Molecular Conformation;Morphology;novel;Nuclear;Nucleic Acids;NUP98 gene;Oncogenes;Oncogenic;Optics;Organelles;Parents;Phase;Phenotype;Process;promoter;Property;protein function;protein protein interaction;Protein Region;Proteins;Recurrence;RNA Polymerase II;Role;Saint Jude Children's Research Hospital;Sarcoma;Source;Structure;submicron;Testing;transcription factor;Transcriptional Regulation;Translating;tumorigenesis

PROJECT_TITLE: Role of Phase separation by fusion oncoproteins in oncogenesis

STUDY_SECTION: MSFB

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


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Lymphatic Research;Lymphoma;Nutrition;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE A challenge of targeting metabolic pathways in cancer is that tumor cells engage various adaptive mechanisms to suffice their metabolic demands or bypass their requirement. Using lymphoid malignancies, including acute lymphoblastic leukemia (ALL) and aggressive B cell lymphoma, as models, we will determine the signaling and chromatin-modifying components that dictate ALL cells' adaptation to asparagine limitation and how glutamine/asparagine availability modulates oncogenic MYC function.

PI_NAMEs: ZHANG, JI  (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: acute lymphoblastic leukemia cell;Acute Lymphocytic Leukemia;Affect;Amino Acids;Anabolism;asparaginase;Asparagine;Aspartate;Aspartate-Ammonia Ligase;B-Cell Lymphomas;Biochemical;biological adaptation to stress;Biological Availability;Bypass;cancer cell;Cancer Patient;cancer therapy;Catabolism;cell growth;Cell Proliferation;Cells;Cellular Metabolic Process;Childhood Acute Lymphocytic Leukemia;Chromatin;Citric Acid Cycle;Clinic;Complex;Consumption;Data;Dependence;deprivation;Development;dietary restriction;DNA;Environment;Enzymes;Face;Gene Expression;Genes;genetic approach;Genetic Transcription;Glutamine;Goals;improved;in vivo;Leukemic Cell;macromolecule;Malignant lymphoid neoplasm;Malignant Neoplasms;Metabolic;Metabolic Pathway;Metabolic stress;Metabolism;Methylation;Modeling;Molecular;mouse model;MYC Family Protein;neoplastic cell;Neoplastic Lymphocyte;new therapeutic target;Non-Essential Amino Acid;Nutrient;Nutrient availability;Oncogenic;Pathway interactions;Patients;Play;Process;Production;programs;Proliferating;promoter;Promoter Regions;Protein Biosynthesis;Proto-Oncogenes;Refractory;Resistance;response;Role;Signal Transduction;Therapeutic;Therapeutic Intervention;therapy resistant;Tissues;transamination;transcription factor;Translating;translational approach;Translational Repression;tumor;tumor growth;Variant;Vascular blood supply

PROJECT_TITLE: Metabolic adaptation in lymphoid malignancies


ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: We propose to define the role of hepatic TAZ in the regulation of glucose and lipid homeostasis in normal and insulin resistant states. Deciphering the molecular mechanisms controlling metabolic regulation is crucial for the understanding of normal physiology and for developing new therapies for metabolic disorders. Therefore, we expect that our studies will advance our understanding of normal physiology as well as the pathogenesis of insulin resistance-associated metabolic disorders, which may uncover new opportunities for therapeutic intervention.

PI_NAMEs: MIAO, JI  (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Binding;Biochemical;Blood Glucose;blood glucose regulation;Cardiovascular Diseases;cell growth;chromatin immunoprecipitation;Data;Diabetes Mellitus;differential expression;Dyslipidemias;Fasting;Fatty Liver;feeding;Gene Expression;Genes;genetic approach;genome-wide;glucocorticoid receptor alpha;Glucose;glucose metabolism;glucose production;Goals;Hepatic;Hepatocyte;High Fat Diet;Homeostasis;Hyperglycemia;Hypertriglyceridemia;insight;Insulin Resistance;Knock-out;Knockout Mice;lipid metabolism;Lipids;Liver;liver metabolism;Liver X Receptor;LXRalpha protein;Metabolic;Metabolic Control;Metabolic Diseases;Molecular;Mus;non-alcoholic fatty liver disease;novel therapeutics;Obesity;Organism;overexpression;Pathogenesis;Pathologic;Pathway interactions;Physiological;Physiology;Plasma;Proliferating;promoter;Protein Binding Domain;Proteins;Regulation;response;Role;Series;Testing;Therapeutic Intervention;therapy development;Tissues;Transcriptional Coactivator with PDZ-Binding Motif;transcriptome sequencing;Triglycerides;Up-Regulation;Work

PROJECT_TITLE: Role of TAZ in metabolic regulation in both normal and insulin resistant states


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Prevention

ORG_CITY: GAINESVILLE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PI_NAMEs: RUMBAUGH, GAVIN R (contact)

PROGRAM_OFFICER_NAME: DOSS, ARGENIA LANISHA NECOLE

PROJECT_TERMS: Adaptive Behaviors;Air;Animal Model;Animals;Area;ASD patient;autism spectrum disorder;awake;Behavior;Behavioral;behavioral impairment;behavioral phenotyping;Biological;Brain;brain abnormalities;Brain region;Cognitive;Darkness;Disease;Echolocation;Electrophysiology (science);Emotions;Environment;Epilepsy;Esthesia;Etiology;experience;Fingers;Functional impairment;Generations;Genes;Genetic Risk;genetic variant;Goals;Head;Heterozygote;Impairment;in vivo;Individual;individuals with autism spectrum disorder;insight;Intervention;Link;Location;Measurement;Measures;Mendelian disorder;Modeling;Motor;Motor Cortex;Motor output;mouse model;Movement;Mus;Mutant Strains Mice;Nervous System;neural;neural circuit;neural network;Neurons;novel;Organ;physical model;Population;Positioning Attribute;Process;Research;Research Project Grants;response;Risk Factors;risk variant;Running;Saccades;Scanning;Sensory;sensory input;sensory processing disorder;sensory system;Silicon;social;Somatosensory Cortex;Source;Structure;Structure of trigeminal ganglion;Study models;SYNGAP1;System;Tactile;Telephone;Testing;Thalamic structure;Thinking;Time;Touch sensation;Vibrissae;Visual Fields

PROJECT_TITLE: Causal Interactions between genetic risk, precise cortical connectivity, and autism-associated behaviors

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Obesity

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Relevance Statement Adipose tissue fibrosis is an integral part of and likely to be a driving force for adipose tissue dysfunction and negative systemic metabolic consequences. Here, we want to focus on dermal adipose tissue, due to its easy accessibility, new genetic models that we have created and the established feature of almost uniform differentiation and de-differentiation of dermal adipocytes; a key aspect on the pathological road to fibrosis in all adipose tissues.

PI_NAMEs: SCHERER, PHILIPP E (contact)

PROGRAM_OFFICER_NAME: HAFT, CAROL R

PROJECT_TERMS: Address;adipocyte differentiation;Adipocytes;adipokines;adiponectin;Adipose tissue;Agonist;Apoptosis;Attenuated;autocrine;Bleomycin;cell type;Cells;Characteristics;Collagen;Communication;Cre lox recombination system;Deposition;Dermal;dermal exposure;Dermis;design;driving force;Ensure;Extracellular Matrix;Fatty acid glycerol esters;feeding;Fibroblasts;Fibrosis;Functional disorder;gain of function;Genetic;genetic approach;genetic manipulation;Genetic Models;Heterogeneity;High Fat Diet;Immune system;in vivo;Inflammation;insight;Label;Laboratories;Leptin;Light;Link;Lipids;Lipolysis;loss of function;Metabolic;Metabolism;Modeling;mouse model;Mus;Mutation;Myofibroblast;Nature;novel;overexpression;paracrine;Pathogenesis;Pathologic;Physiological;Population;PPAR gamma;precursor cell;prevent;Process;Production;promoter;Reporting;response;Role;rosiglitazone;single cell sequencing;Skin;skin fibrosis;skin lesion;System;Thick;Time;Tissues;Topical application;transdifferentiation;Translating;Up-Regulation

PROJECT_TITLE: Physiological Role of Dedifferentiating Dermal Adipose Tissue

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Bioengineering;Chronic Pain;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects

ORG_CITY: MILWAUKEE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE The sensory neuron-specific mechanisms underlying mechanosensation in normal and pathological states are not well known. Piezo1 is a mechanosensitive cation channel that is a candidate mechanism in sensory neuron- mediated somatosensation. This proposal examines whether sensory neuron Piezo1 ion channels mediate peripheral tactile sensation and mechanical hypersensitivity following peripheral nerve injury.

PI_NAMEs: EHLERS, VANESSA  (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Action Potentials;Afferent Neurons;Agonist;Animals;Attention;Behavioral;Behavioral Assay;Cations;Cells;cellular targeting;Characteristics;comparative;Cutaneous;Data;Detection;Development;Electrophysiology (science);Esthesia;experimental study;Fiber;Freund's Adjuvant;Goals;Homologous Gene;Human;Hyperalgesia;Hypersensitivity;Inflammation;inflammatory pain;Injury;Ion Channel;Ion Channel Gating;keratinocyte;Measures;mechanical allodynia;mechanical force;Mechanical Stimulation;mechanical stimulus;Mechanics;Mechanoreceptors;mechanotransduction;Mediating;Mus;Nature;Nerve;nerve injury;Neurons;Nociception;Organism;overexpression;Pain;Pain management;pain sensation;painful neuropathy;patch clamp;Pathologic;Peripheral;Peripheral nerve injury;Peripheral Nerves;Peripheral Nervous System;Peripheral Nervous System Diseases;peripheral pain;Persistent pain;pharmacologic;Piezo 1 ion channel;Piezo 2 ion channel;Play;Prevalence;Proprioception;release of sequestered calcium ion into cytoplasm;Reporting;response;Rodent;Role;severe injury;single-cell RNA sequencing;Skin;somatosensory;spared nerve;Spinal Ganglia;Stimulus;Structure of tibial nerve;System;Tactile;Testing;Tissues;Touch sensation;Transcript;Transgenic Mice;translational potential;transmission process;Traumatic Nerve Injury;Wild Type Mouse;Work

PROJECT_TITLE: Role of Piezo1 in Mechanical Touch and Nociception

STUDY_SECTION: NST

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


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: LA JOLLA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative The proposed research is relevant to public health because defects in endocytosis are at the heart of many diseases including cancer, neurodegeneration, and heart disease. Therefore, the proposed research plan to elucidate the fun- damental biophysical principles underlying endocytosis is relevant to the part of NIH's mission that seeks to develop fundamental knowledge that will mitigate the burden of human disease. Further, the proposed work studies an in- novative method to modulate endocytosis using substrate curvature, paving the way for the potential design of new strategies to treat multiple pathologies.

PI_NAMEs: RANGAMANI, PADMINI  (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Actins;Address;Affect;Affinity;Binding;Binding Proteins;Biochemical;Biophysics;Cell membrane;Cells;Clathrin;Communities;Computer Models;computerized tools;Coupling;Cytoskeleton;Data;Data Set;Defect;density;design;Development;Diffusion;Disease;Down-Regulation;Drug Delivery Systems;Endocytosis;experimental study;Explosion;Extracellular Fluid;Extracellular Space;Feedback;Filament;Generations;Genes;Goals;Heart;Heart Diseases;Homeostasis;human disease;Imaging technology;in vivo;in vivo evaluation;innovation;insight;Knowledge;Lipid Bilayers;Literature;Malignant Neoplasms;Mammalian Cell;mathematical methods;Measures;Mechanics;Mediating;Membrane;Membrane Lipids;membrane model;Membrane Proteins;Methods;Microfilaments;Mission;model development;Modeling;Modification;Molecular;Morphology;multi-scale modeling;nanomedicine;NanoPillar;Nerve Degeneration;open source;Pathology;Pattern;Play;polymerization;Polymers;predictive modeling;Principal Investigator;Probability;Process;Property;Proteins;Public Health;Radial;Receptor Signaling;Regulation;repository;Research;Role;Scheme;Shapes;simulation;Site;spatiotemporal;Structure;Surface;Testing;Theoretical model;United States National Institutes of Health;uptake;Vesicle;Work;Yeasts

PROJECT_TITLE: Modeling and analysis of the mechanochemical processes that govern clathrin-mediated endocytosis

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Genetics;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Narrative: By defining the relationship between macrophage polarization and protective effector function and how this relationship is regulated, this proposal has the potential to identify new therapeutic targets to control fungal growth. This approach should address the decades-long failure to make major improvements in the outcome of PcP. The goal of this project is directly responsive to the NIH mission statement of the need to generate basic science data that can be developed into translational studies designed to improve patient care. TW19

PI_NAMEs: WRIGHT, TERRY W (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;adaptive immunity;Address;Adrenal Cortex Hormones;Alveolar Macrophages;anti-fungal agents;Antibiotic Therapy;Area;Basic Science;Candidate Disease Gene;candidate identification;CD4 Positive T Lymphocytes;Cells;Characteristics;Chitinase;Chromosome Mapping;Data;Death Rate;Disease;drug discovery;Event;Failure;FVB Mouse;Genetic;genomic locus;Goals;Growth;Host Defense;Immunity;Immunocompetent;Immunocompromised Host;Impairment;improved;In Vitro;in vivo;Inbred Strains Mice;Inbreeding;Infection;Inflammatory;Ingestion;inhibitor;Injury;insight;Interferon Type II;Knowledge;Laboratories;Life;Lung;Macrophage;Maps;Mediating;Mission;Modeling;mouse model;Mouse Strains;Mus;Mycoses;Natural Immunity;new therapeutic target;novel;novel therapeutic intervention;Organism;Outcome;pathogen;pathogenic fungus;Patient Care;Pattern recognition receptor;Phagocytes;Phagocytosis;Phagosomes;Phenotype;Pneumocystis;Pneumocystis carinii Pneumonia;Pneumocystis Infections;Predisposition;Production;Productivity;programs;protein expression;Proteins;Quantitative Trait Loci;rational design;Reagent;receptor;Receptor Protein-Tyrosine Kinases;Regulation;Research;Research Design;Resistance;resistance gene;Resistance to infection;respiratory;Role;Sentinel;Surface;T-Lymphocyte;Testing;Therapeutic;Time;tool;translational study;transmission process;treatment strategy;United States National Institutes of Health;Work

PROJECT_TITLE: Novel mechanisms of Alveolar Macrophage-Dependent Antifungal Innate Immunity

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Neurosciences;Pain Research

ORG_CITY: BOSTON

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Nociceptor neurons are specialized to sense noxious stimuli and protect mammals from danger. We investigate whether gut-innervating nociceptors play a crucial role in protecting the gut barrier at homeostasis and during bacterial invasion by signaling to epithelial cells and immune cells.

PI_NAMEs: CHIU, ISAAC MING-CHENG (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Ablation;Afferent Neurons;Autoimmune Diseases;Bacteria;Calcitonin Gene-Related Peptide;Capsaicin;Cell Physiology;Cells;Cellular biology;Central Nervous System;Citrobacter;Citrobacter rodentium;Data;designer receptors exclusively activated by designer drugs;dietary;Disease;Enteral;enteric pathogen;Epithelial Cells;Epithelium;experimental study;Functional disorder;gain of function;Gastroenterology;gastrointestinal;Gastrointestinal Diseases;gastrointestinal epithelium;Gastrointestinal tract structure;Genetic;Goblet Cells;gut microbiota;Homeostasis;Host Defense;Immune;Immune response;Immunity;Immunology;Infection;Inflammation;Inflammatory;innovation;insight;interdisciplinary approach;Intestines;Invaded;Lead;Ligands;loss of function;M cell;Maintenance;Mammals;Maps;Mediating;Mediator;Microbe;microbial;Molecular;molecular phenotype;Mucous body substance;Mus;mustard oil;Nervous System;neural;Neurobiology;neuroimmunology;Neurons;Neuropeptides;neurotransmission;Nociception;Nociceptors;novel;novel strategies;Pain;pain sensation;pathogen;Pathogenicity;Peptide Signal Sequences;Peripheral;Peripheral Nerves;Peyer's Patches;Physiology;Play;Population;Production;RAMP1;receptor;Reflex action;Regulation;Role;Salmonella;Salmonella typhimurium;Signal Transduction;Stimulus;T-Lymphocyte;Testing;Tissues;villin

PROJECT_TITLE: Nociceptor neuron regulation of gastrointestinal barrier protection and host defense

STUDY_SECTION: GMPB

STUDY_SECTION_NAME: Gastrointestinal Mucosal Pathobiology Study Section[GMPB]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Immunotherapy;Radiation Oncology;Women's Health Research

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: NARRATIVE Low levels of oxygen (hypoxia) within a tumor is a barrier to effective therapy with radiation and immune checkpoint blockade. We have developed some new drug like compounds that can reduce the consumption of oxygen within the tumor and reduce hypoxia. We now propose to test these in model tumors to see if they sensitize to treatment with radiation or PD1 blockade.

PI_NAMEs: DENKO, NICHOLAS C. (contact);LI, ZIHAI

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Acceleration;Adjuvant;Affect;anti-cancer treatment;anti-PD1 therapy;Antigens;Biophysics;Blood;Blood Pressure;Blood Vessels;Brain Neoplasms;cancer infiltrating T cells;Cancer Model;cancer therapy;cardiovascular effects;Cell Hypoxia;cell killing;Cell Respiration;Cells;Cerebrovascular Spasm;Characteristics;chemotherapy;Chimeric Proteins;Chronic;Clinical;Complex;Data;design;Dose;Drops;Drug usage;drug-like compound;effective therapy;Effectiveness;Equilibrium;Erectile dysfunction;exhaustion;FDA approved;Flow Cytometry;Gastrointestinal tract structure;Heterotopic Transplantation;Human;Hypoxia;Immune;immune cell infiltrate;immune checkpoint blockade;Immune Evasion;Immunocompetent;Immunophenotyping;Immunotherapy;improved;in vivo;inhibitor;insight;Kinetics;Lead;Luciferases;Malignant Neoplasms;mammary epithelium;Measures;Metabolic;Mitochondria;Modality;Modeling;mouse model;Mus;Muscle relaxants;Mutation;neoplastic cell;Normal tissue morphology;novel;novel therapeutics;orthotopic breast cancer;Oxygen;Oxygen Consumption;Papaver;Papaverine;Parents;PD-1 blockade;Perfusion;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacodynamics;Phosphodiesterase Inhibitors;phosphoric diester hydrolase;programmed cell death protein 1;Proteins;Publishing;Radiation;radiation response;Radiation therapy;Radiation Tolerance;Radiation-Sensitizing Agents;Radio;Radiosensitization;Relaxation;Reporter;Reporting;Resistance;RNA analysis;Rodent;Safety;small molecule;Smooth Muscle;Solid Neoplasm;stemness;Structure;T-Lymphocyte;Testing;Theft;theories;Transplantation;tumor;tumor hypoxia;tumor microenvironment;Tumor Oxygenation;vascular bed;Vascular resistance;Vasospasm

PROJECT_TITLE: Overcoming hypoxic resistance to anti-cancer therapy

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics

ORG_CITY: Boulder

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative The goal of this application is to develop a new technology platform for delivering proteins and nucleic acids to the intracellular space to alter cellular or organismic phenotypes transiently or permanently in a dose-dependent manner.

PI_NAMEs: LIU, XUEDONG  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: adaptive immune response;Address;Antibodies;Area;Basic Science;Biological Products;Biomedical Research;Bypass;CD47 gene;Cell Line;Cell membrane;Cell Nucleus;Cells;cellular engineering;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;Complement;Complement component C1;Cytosol;design;Diffusion;Dose;Effectiveness;Electroporation;Encapsulated;Endosomes;Engineering;Enzymes;Exhibits;exosome;Extracellular Space;extracellular vesicles;Gene Delivery;gene function;Goals;GTP-Binding Proteins;Heterogeneity;Human;human disease;Immune response;immunogenicity;improved;In Vitro;in vivo;innovation;interest;Intracellular Space;Knock-out;macromolecule;Measures;Mediating;Methods;Microinjections;microvesicles;Modification;Molecular Weight;nanobodies;nanoengineering;new technology;novel therapeutic intervention;novel therapeutics;Nucleic Acids;Pathway interactions;Phenotype;Production;protein aggregation;protein degradation;protein function;Proteins;Publishing;Research;Resistance;Ribonucleoproteins;RNA Interference;RNA Sequences;Safety;Specificity;success;Surface;System;systemic toxicity;Technology;technology platform;Testing;Therapeutic;Time;tool;Toxic effect;Transfection;translational medicine;treatment strategy;ubiquitin-protein ligase;vesicular stomatitis virus G protein;Viral

PROJECT_TITLE: Programmable Microvesicles for Intracellular Macromolecule Delivery

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


NIH_SPENDING_CATS: Biotechnology;Genetics;Hematology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE Somatic mutations arising in clonal hematopoiesis and myelodysplastic syndromes (MDS) are a major public health problem characterized by dysfunctional hematopoietic stem and progenitor cells, abnormal blood production, and a risk of progression to acute leukemia. Deletions or mutations of CUX1, encoding a highly- conserved transcription factor, are recurrent in clonal hematopoiesis and MDS. We aim to understand the mechanism by which CUX1 levels regulate hematopoietic development with the goal of informing new interventions to improve the quality of life for patients with these genetic changes.

PI_NAMEs: MCNERNEY, MEGAN  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Acute leukemia;Address;Anemia;Binding;Biological Assay;Blood;cell behavior;Cell surface;Cells;Chromatin;chromatin protein;chromatin remodeling;Chromatin Remodeling Factor;chromosome 7q loss;cytopenia;Data;Defect;Development;Developmental Biology;Developmental Gene;Disease;DNA;dosage;Dysmyelopoietic Syndromes;Enhancers;Epigenetic Process;Erythroid;Exhibits;experimental study;Family;Fluorochrome;functional genomics;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Genomic approach;Goals;Hematology;Hematopoiesis;Hematopoietic;hematopoietic stem cell differentiation;hematopoietic stem cell fate;Hematopoietic stem cells;Heterogeneity;homeodomain;Human;improved;in vivo;Intervention;Investigation;knock-down;Knowledge;Lead;Length;loss of function mutation;Lymphoid;Measures;Megakaryocytes;Methodology;Modeling;Molecular;Monosomy 7;Multipotent Stem Cells;Mus;Mutation;Myelopoiesis;novel;novel therapeutics;Nucleosomes;Pathogenesis;Patients;Prevalence;Process;Production;progenitor;Prognosis;progression risk;Proliferating;Proteins;Public Health;Quality of life;recruit;Recurrence;Reporter;Reporting;Role;self-renewal;Series;single cell analysis;SMARCE1 gene;Somatic Mutation;stem;stem cell function;stem cells;Tertiary Protein Structure;Testing;Therapeutic;Therapeutic Intervention;transcription factor;Transcriptional Regulation;transcriptome;tumor;Tumor Suppressor Proteins;Up-Regulation;Work

PROJECT_TITLE: Establishing CUX1 as a determinant of hematopoietic stem cell fate

STUDY_SECTION: HTBT

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