ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: Project Narrative Cancer cells encase themselves in a soft material coating, termed the cellular glycocalyx, with specific properties that protect against recognition and destruction by the immune system. In this project, we will investigate the mechanisms through which the cancer cell glycocalyx physically protects against attack by Natural Killer (NK) cells, key frontline defenders of the human immune system that guard against cancer. The new mechanistic insight will inform the development of engineered NK cell therapeutics that are intended to overcome the protective glycocalyx barrier of cancer cells and improve patient outcomes.

PI_NAMEs: PASZEK, MATTHEW J (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Adoptive Cell Transfers;Attention;Biochemical;Biocompatible Coated Materials;Biophysics;Biopolymers;cancer cell;cancer immunotherapy;cancer therapy;Cations;Cell Communication;cell killing;Cell surface;cell type;Cells;Cellular biology;cellular engineering;cellular microvillus;Cessation of life;chimeric antigen receptor;chimeric antigen receptor natural killer cells;Clinical;clinical application;clinically relevant;Cytolysis;Cytoplasmic Granules;cytotoxic;cytotoxicity;design;Detection;Development;Dimensions;Effector Cell;Elements;Endowment;engineered NK cell;Engineering;Environmental Monitoring;Enzymes;extracellular;Glycocalyx;glycosylation;Goals;Human;Image;imaging approach;Imaging Techniques;Immune;Immune Evasion;Immune mediated destruction;Immune system;immunoengineering;Immunotherapy;improved;Individual;innovation;insight;interest;Interference Microscopy;Intrinsic factor;Knowledge;Malignant Neoplasms;Measures;Mediating;Metabolic;Molecular;mucinase;Mucins;Mucolytics;nanometer;nanoscale;Natural Killer Cells;neoplastic cell;Oncogenic;overexpression;Pathway interactions;Patient-Focused Outcomes;Pattern;Penetration;Physical Function;physical property;Polymers;Polysaccharides;Predisposition;Process;programs;Property;receptor;Receptor Signaling;Refractory;Reporter;Reporting;Resistance;Role;Scanning;Signal Transduction;Structure;superresolution imaging;Surface;Techniques;Technology;Testing;Therapeutic;Thick;tool;Tumor Antigens;uptake

PROJECT_TITLE: Physical Resistance to Immune Cell Attack by the Cellular Glycocalyx

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-S(09)F]


ADMINISTERING_IC: AG

ARRA_FUNDED: N

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurodegenerative;Neurosciences;Patient Safety;Prevention;Primary Health Care;Telehealth

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative Primary care access and continuity of care improve outcomes for older adults with multimorbidity (multiple chronic conditions), so a recent decline in primary care office visit rates – likely due in part to barriers attending office visits – raises concerns about these two core functions of high-value outpatient care. The proposed study will determine if multimorbid older adults with Alzheimer’s Disease (AD) and AD-related dementia (AD/ADRD) and social risk factors were at greater risk of office visit barriers; assess how expansion of virtual care catalyzed by the Covid-19 pandemic affects primary care use for those with AD/ADRD and social risk factors; and determine whether a novel continuity measure that includes virtual care is associated with preventable hospitalizations among multimorbid older adults. The results of this research – using national claims-linked Medicare survey data and claims-linked electronic health record data in a large Medicare Accountable Care Organization – will identify policy and delivery changes needed to promote high-value outpatient care and improve outcomes among multimorbid older adults.

PI_NAMEs: GANGULI, ISHANI  (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: accountable care organization;Address;Adult;Affect;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Ambulatory Care;Award;beneficiary;care delivery;care outcomes;career;Caring;Chronic;clinical training;Continuity of Patient Care;cost;COVID-19 pandemic;COVID-19 pandemic effects;Data;Data Analyses;Drops;Electronic Health Record;Evaluation;experience;Fee-for-Service Plans;Future;Geriatrics;Goals;Health;Health Services;Health Services Accessibility;Health Services Research;Health system;Hospitalization;Hospitals;human old age (65+);Improve Access;improved;improved outcome;Incentives;indexing;innovation;Insurance Claim Review;Internet;Knowledge;Link;Low income;Measures;medical schools;Medicare;Medicare claim;Medicine;Memory;Mentored Patient-Oriented Research Career Development Award;Mentorship;Methods;Modeling;multiple chronic conditions;novel;Office Visits;older adult;Organizational Models;Outcome;pandemic disease;Patients;payment;Policies;Policy Maker;Population;Populations at Risk;post-pandemic;pre-pandemic;Primary Care;Primary Care Physician;primary care provider;primary care setting;primary care visit;professor;Quality of Care;Quasi-experiment;racial minority;Reporting;Research;Research Personnel;Risk;Risk Factors;Role;Secure;social;Surveys;Telephone;Touch sensation;Training;video visit;virtual;virtual assessment;virtual delivery;virtual healthcare;Visit;Woman;Work

PROJECT_TITLE: The Role of Virtual Care in Improving Primary Care Access and Continuity for At-Risk Multimorbid Older Adults

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Clinical Aging Study Section[NIA-C]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Aging;Building Research Capacity at Institutions with Limited NIH Funding;Physical Activity;Physical Injury - Accidents and Adverse Effects

ORG_CITY: SAN BERNARDINO

ORG_DEPT: BIOLOGY

ORG_NAME: CALIFORNIA STATE UNIV SAN BERNARDINO

ORG_STATE: CA

PHR: Project Narrative The percentage of the US population over the age of 60 is growing steadily, and issues affecting quality of life and mobility of the elderly are of significant concern. Tendinopathy in later stage aging may be impacted by adolescent exercise, but the relationship between these phenomena is not well understood. This project aims to test if early life exercise relates to improved tendon performance in late life, and seeks to understand the contributing mechanisms.

PI_NAMEs: HORNER, ANGELA  (contact)

PROGRAM_OFFICER_NAME: BECK, LAWRENCE A

PROJECT_TERMS: Address;Adolescent;Adult;Advanced Glycosylation End Products;Affect;Age;age effect;age related decline;aged;Aging;aging population;Area;Biological Assay;Cell Density;Cellular Structures;cohort;Collagen Fibril;Dimensions;Elderly;Exercise;Exercise Therapy;exercise training;Failure;falls;Future;Growth;Harvest;healing;histological slides;Histology;Human;improved;injured;Isotopes;Label;late life;Life;Locomotion;Lysine;mechanical load;mechanical properties;Mechanics;middle age;Mitosis;Mobility decline;Morphology;mouse model;Mus;Musculoskeletal;Pathway interactions;Performance;Peripheral;Population;Preparation;protein degradation;Protocols documentation;Quality of life;Recording of previous events;repaired;Research;Resistance;response;Rodent;Role;sedentary;skeletal;stable isotope;Stress;Tendinopathy;tendon development;Tendon Injuries;Tendon structure;Testing;Tissues;Training

PROJECT_TITLE: Early life exercise effects on tendon maturation and resistance to late life tendinopathies


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Clinical Research;Data Science;Epilepsy;Neurodegenerative;Neurosciences;Patient Safety;Precision Medicine;Prevention

ORG_CITY: PHILADELPHIA

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative The proposed research is relevant to public health because over 20 million people worldwide suffer from focal drug-resistant epilepsy and are potential candidates for cure with epilepsy surgical interventions or devices. Upon successful completion of the proposed research, we expect our contribution to be the development of a biomarker to predict outcomes to responsive neurostimulation device therapy for epilepsy. Our findings may inform physicians and patients on the most effective therapy for an individual patient with drug-resistant epilepsy and pave the way to bringing quantitative rigor into clinical decision making for epilepsy patients.

PI_NAMEs: DAVIS, KATHRYN ADAMIAK (contact)

PROGRAM_OFFICER_NAME: TAYLOR-BURDS, CAROL C

PROJECT_TERMS: Acceleration;Address;Adopted;Adoption;American;analysis pipeline;Biological Markers;biomarker discovery;biomarker signature;biomarker validation;Brain;candidate marker;Chronic;Clinic;Clinical;clinical center;Clinical Data;clinical decision-making;clinical research site;Clinical Trials;cloud based;Collaborations;computational neuroscience;Data;data exchange;data mining;Data Set;Data Store;Decision Making;Development;Devices;effective therapy;Electroencephalography;Electrophysiology (science);Engineering;Ensure;Epilepsy;Evaluation;experience;FDA approved;federated data;Freedom;Frequencies;geographically distant;Goals;hands-on learning;Heterogeneity;Image;Implant;implantable device;implantation;improved;Individual;individual patient;Industry;Industry Collaboration;industry partner;Infrastructure;innovation;Institutional Review Boards;Intractable Epilepsy;Machine Learning;Medical;Metadata;Modeling;Monitor;multimodal data;multimodality;Nervous System Disorder;Network-based;neural;neuroimaging;novel;Operative Surgical Procedures;Outcome;outcome prediction;participant enrollment;patient population;patient privacy;patient response;Patient Selection;Patient-Focused Outcomes;Patients;personalized biomarkers;Persons;Pharmaceutical Preparations;Phase;Physicians;predicting response;predictive marker;predictive signature;preservation;Prior Therapy;Privatization;Prognostic Marker;prospective;Public Health;Research;Resistance;response;Running;screening;Secure;Seizures;Site;Standardization;success;Testing;Therapeutic Effect;Time;Tonic-Clonic Epilepsy;Training;translational neuroscience;treatment response;Work

PROJECT_TITLE: Biomarkers to Predict Outcome from Responsive Brain Stimulation for Epilepsy

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders A Study Section[NSD-A]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Infectious Diseases;Liver Disease;Microbiome;Substance Misuse

ORG_CITY: LA JOLLA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative Alcohol-associated liver disease affects several million people in the United States. Gut-derived bacterial products are necessary for progression of alcohol-associated liver disease, but changes in the intestinal fungi are poorly characterized. Understanding the mechanisms by which intestinal fungi promote alcohol-associated liver disease would greatly enhance our ability to design preventive and therapeutic interventions for patients.

PI_NAMEs: SCHNABL, BERND G. (contact)

PROGRAM_OFFICER_NAME: WANG, JOE

PROJECT_TERMS: adaptive immunity;Adoptive Transfer;Affect;Alcohol abuse;alcohol response;alcohol use disorder;Alcoholic Liver Diseases;Alcoholism;Alcohols;anti-fungal agents;Antigens;Bacteria;bacteriome;Belgium;Binding;California;Candida;Candida albicans;CD4 Positive T Lymphocytes;Cells;Chronic;Circulation;cohort;Data;design;Developed Countries;Disease;dysbiosis;Ethanol;Etiology;Experimental Animal Model;feeding;Functional disorder;fungal microbiota;fungus;Gene Modified;Genetic Transcription;Germany;Glucans;Goals;Growth;gut microbiome;gut-liver axis;Health;Hepatic;Human;IL17 gene;Immune response;Immunity;Infrastructure;innovation;insight;Interdisciplinary Study;Intervention;Intestinal permeability;Intestines;Kupffer Cells;Laboratories;Ligation;Liver;Liver diseases;liver inflammation;liver injury;Macrophage;Malassezia;Mediating;Medical;Methods;microbial;microbiome research;microbiome sequencing;microbiota;migration;Molecular;Morbidity - disease rate;mortality;mouse dectin-2;mouse model;Mus;mycobiome;Natural Immunity;Nature;new therapeutic target;novel;Patients;Persons;pharmacologic;Population;Portal vein structure;prevent;preventive intervention;Principal Investigator;Publications;receptor;Research;Research Personnel;Ribosomal DNA;Role;Steatohepatitis;Supplementation;T cell response;T-Cell Receptor;Testing;Therapeutic Intervention;Transgenic Mice;United States;Universities;University Hospitals;Virulence Factors;Virus

PROJECT_TITLE: The Role of the Intestinal Mycobiome in Alcoholic Liver Disease

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ADMINISTERING_IC: CA

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Women's Health Research

ORG_CITY: PITTSBURGH

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Breast cancer ranks second among cancer deaths in women in the United States. In this project, we will examine the underlying mechanisms of how profilin1, a major actin cytoskeleton regulatory protein, controls the early steps of breast cancer metastasis. Specifically, we will identify how Pfn1 dysregulation alters the signaling pathways at the cell membrane-cytosol interface to promote specific dissemination-promoting steps leading to tumor cell escape from the primary tumor. A successful completion of this study will yield novel insights into fundamental tumor cell biology, provide molecular underpinnings of basic adenocarcinoma behaviors that lead to progression in metastatic breast cancer.

PI_NAMEs: ROY, PARTHA  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Actin-Binding Protein;Actins;Adenocarcinoma;Animals;antagonist;arm;Behavior;Binding;Biochemical;Biological Assay;Biology;Biosensor;Breast Cancer Cell;breast cancer metastasis;cancer cell;Cell membrane;cell motility;Cells;Cessation of life;Clinical;Cytoskeleton;Cytosol;Data;Diagnosis;Diffusion;Down-Regulation;Extracellular Matrix;Family;gain of function;Generations;genetic regulatory protein;Goals;Human;Hydrolysis;Image;Immunofluorescence Immunologic;Immunohistochemistry;In Vitro;in vivo;INPPL1 gene;insight;intravital imaging;Invaded;Knowledge;Link;Lipids;live cell imaging;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Membrane;Metastatic breast cancer;migration;Modeling;Molecular;Motility;mouse model;Neoplasm Metastasis;neoplastic cell;novel;Pathway interactions;Phenotype;Phosphatidylinositols;phosphoinositide-3,4,5-triphosphate;phosphoinositide-3,4-bisphosphate;Phospholipase C;Phosphoric Monoester Hydrolases;Physiological;PIK3CG gene;Primary Neoplasm;profilin;profilin 1;Proline;Protein Dephosphorylation;Protein Dynamics;Proteins;Proto-Oncogene Proteins c-akt;PTEN gene;recruit;Regulation;residence;Resolution;Role;Sampling;Signal Pathway;Signal Transduction;single molecule;Study models;Testing;Time;Tumor Cell Biology;Tumor Cell Invasion;tumor progression;United States;Up-Regulation;vasodilator-stimulated phosphoprotein;Woman;Women's mortality;Zebrafish

PROJECT_TITLE: Profilin biology in breast cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Osteoporosis;Prevention;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative PTH1-34 (Teriparatide, Forteo®) and Abaloparatide (Tymlos®) target the PTH receptor and are approved anabolic drugs for Osteoporosis, a widespread bone fragility chronic condition linked to aging and characterized by dysfunctions of cells in bone, often associated with an increase in bone marrow fat. Bone forming cells (osteoblasts) and fat cells (adipocytes) share a common precursor, and understanding PTH influence on the choice of cells to become a bone or a fat cell is important for the development of future treatments for osteoporosis, fracture healing as well as for the cell therapy aimed at bone regeneration. This grant will investigate whether preventing bone marrow fat will favor bone formation in response to PTH treatment.

PI_NAMEs: BARON, ROLAND E (contact);ROSEN, CLIFFORD JAMES

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: adipocyte differentiation;Adipocytes;Adipose tissue;Aging;Animal Model;bone;Bone Density;bone fracture repair;bone fragility;bone loss;Bone Marrow;bone marrow mesenchymal stem cell;bone mass;Bone Regeneration;bone repair;Bone Resorption;Cell Lineage;Cell Therapy;Cells;Chronic;Clinic;Clinical;clinically relevant;Development;Elderly;Equilibrium;Estrogen deficiency;Event;Fatty acid glycerol esters;Forteo;Fracture;fracture risk;Functional disorder;Future;Genes;Glucocorticoids;Goals;Grant;health economics;Homeostasis;Human;Impairment;improved;Injections;innovation;Link;lipid biosynthesis;Maintenance;Marrow;mechanical load;Mediating;Mesenchymal Stem Cells;Molecular;novel;Obesity;osteoblast differentiation;Osteoblasts;Osteocytes;Osteogenesis;Osteoporosis;Osteoporosis prevention;Parathyroid Hormone Receptor;parathyroid hormone-related protein;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacotherapy;Play;prevent;Process;receptor;Receptor Signaling;Regulation;Repression;response;Rodent;Role;Signal Pathway;Signal Transduction;skeletal;Skeleton;socioeconomics;stem cell fate specification;Testing;Therapeutic Effect;Therapeutic Uses;transcription factor;treatment effect;WNT Signaling Pathway;Work

PROJECT_TITLE: Mechanism of action of PTH: New signaling components that regulate bone formation and bone marrow fat

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Breastfeeding, Lactation and Breast Milk;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Fetal Alcohol Spectrum Disorders (FASD);Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Substance Misuse;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_DEPT: NUTRITION

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative  We propose to design, pilot test, and validate the efficacy of innovative new multivariate protocols for estimating risk for fetal alcohol spectrum disorders (FASD). In the R61 Phase we will research, create, design, and pilot test new protocols for: 1) interviewing mothers (with biomarker validation) to determine daily/weekly prenatal alcohol exposure across pregnancy and postpartum alcohol use during breastfeeding; 2) determining maternal experience with stress, trauma, and mental health status during pregnancy and their contribution to FASD diagnostic traits; 3) interviewing fathers regarding paternal traits that contribute to risk for FASD; and 4) establishing a comprehensive, summary FASD risk score from the above innovations when combined with multiple other empirically-established variables of risk. The R33 Phase will draw on our existing clinical epidemiology infrastructure, the experience of our multi-disciplinary team, and the participants in existing longitudinal cohorts to assess the efficacy of multivariate FASD risk assessment in two applications: A) a multivariate assessment of FASD risk via a prospective study of 200 women recruited from prenatal clinics, and their offspring who will be assessed postpartum for FASD traits; and B) and linking retrospectively-collected multivariate FASD risk information with data from two existing cohorts of mothers and their children who have been previously assessed for FASD and the severity of their physical, neurodevelopmental, and behavioral traits.

PI_NAMEs: CHEATHAM, CAROL L (contact)

PROGRAM_OFFICER_NAME: BALACHOVA, TATIANA NIKOLAYEVNA

PROJECT_TERMS: Adolescence;Age;Age Months;alcohol and other drug;Alcohol consumption;alcohol exposure;Alcohols;Anxiety;Behavioral;biomarker validation;Birth;Breast Feeding;Cannabis;Categories;Child;child bearing;Childhood;Clinic;Clinical assessments;clinical epidemiology;cohort;Conceptions;Consent;Consultations;Data;design;Development;Diagnosis;Diagnostic;Dietary intake;disorder risk;Distal;Drug usage;Dysmorphology;efficacy evaluation;efficacy trial;efficacy validation;Environmental and Occupational Exposure;Environmental Exposure;Environmental Risk Factor;Epigenetic Process;Etiology;Event;experience;Exposure to;Fathers;Feedback;Fetal Alcohol Exposure;Fetal Alcohol Spectrum Disorder;Genetic;Goals;Growth;Growth Disorders;Health;Health Status;Human Milk;improved;Individual;Infrastructure;innovation;insight;Interview;Knowledge;Learning;Life;Link;Longitudinal cohort;Longitudinal cohort study;maternal alcohol use;Measures;Mental Depression;Mental Health;Methamphetamine;Methodology;Methods;Moods;Mothers;multidisciplinary;novel;offspring;Outcome;Parents;Participant;Pharmaceutical Preparations;Phase;pilot test;Post-Traumatic Stress Disorders;Postpartum Period;Predisposition;Pregnancy;prenatal;Prevention;prospective;Prospective Studies;Prospective, cohort study;Protocols documentation;Questionnaires;Recording of previous events;recruit;remediation;Research;Research Methodology;response;Retrospective Studies;Risk;Risk Assessment;Risk Estimate;Risk Factors;Severities;social;Specificity;Stress;Techniques;Teratogens;Time;Toxic Environmental Substances;trait;Trauma;Validation;Violence;Woman

PROJECT_TITLE: Adventures in the Design and Trial of an Innovative FASD Risk Assessment: Integrating Known Risks with New Measures of Weekly Prenatal Alcohol Exposure, Maternal Mental Health, and Paternal Alcohol

STUDY_SECTION: AA

STUDY_SECTION_NAME: Epidemiology, Prevention and Behavior Research Study Section[AA-2]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Genetics;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE Alzheimer’s disease is considered the most costly and burdensome disease in the U.S, and its public health impact will only grow with the increase of older adults in the next decade. Despite the protracted progression of AD brain pathology, little is known about its early temporal course from middle to older age, particularly for in vivo neuroimaging indices. With neuroimaging, cognitive, and biomarker data beginning when participants were in their 50s, the longitudinal VETSA MRI project stands to advance progress toward early identification, and in turn, toward improving quality of life and reducing societal burden.

PI_NAMEs: DALE, ANDERS M;ELMAN, JEREMY A (contact);FENNEMA-NOTESTINE, CHRISTINE ;KREMEN, WILLIAM S.

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Adult;Age;Aging;aging brain;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid beta-Protein;apolipoprotein E-4;arterial spin labeling;Biological Markers;Brain;Brain Pathology;Brain region;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;cerebrovascular health;cerebrovascular pathology;Cognition;Cognitive;cohort;Consensus;cost;Data;data acquisition;Data Collection;Dementia;Deposition;design;Development;Diabetes Mellitus;Diffusion Magnetic Resonance Imaging;Disease;Disease Marker;Disease Progression;Early identification;Education;Etiology;Funding;Genetic;Genetic Variation;genome-wide;Genotype;Goals;Grant;Health;Hour;human old age (65+);Hypertension;hypoperfusion;Impaired cognition;improved;in vivo;indexing;Individual;interest;Knowledge;life span;Link;locus ceruleus structure;Magnetic Resonance Imaging;Measures;Mediating;Medical;middle age;mild cognitive impairment;Modality;modifiable risk;multimodality;Nerve Degeneration;neuroimaging;novel;older adult;Onset of illness;Outcome;Participant;Pathologic;Pathology;Pattern;Perfusion;Phase;Plasma;Population;Positioning Attribute;Predisposition;prevent;Process;prodromal Alzheimer's disease;protective factors;psychosocial;Public Health;Quality Control;Quality of life;Resources;Risk;Risk Factors;Sampling;Savings;Signal Transduction;Site;Smoking;Source;Structure;tau Proteins;tau-1;Testing;Thick;Time;Twin Multiple Birth;Twin Studies;United States National Institutes of Health;vascular risk factor;Vietnam;virtual;White Matter Hyperintensity;Work

PROJECT_TITLE: The VETSA Longitudinal MRI Twin Study of Aging (VETSA MRI 4)

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project Narrative Our genetic information must be duplicated accurately each time a cell in our body divides and distributed appropriately to the daughter cells in order to prevent the accumulation of mutations and preserve the integrity of the genome. This proposal seeks to understand how various pathways that act to preserve genomic integrity during DNA replication operate and interact with one another and how the topoisomerases and condensins that manage chromosome conformation and segregation cooperate to accomplish their task.

PI_NAMEs: MARIANS, KENNETH J (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Amino Acid Sequence;Binding Proteins;Cell Cycle;Cell division;Cells;Cellular Stress;Chromatin;Chromatin Loop;Chromosomal Duplication;Chromosome Segregation;Chromosome Structures;Chromosomes;Complex;condensin;daughter cell;DNA;DNA biosynthesis;DNA replication fork;DNA Sequence;DNA Topoisomerase IV;DNA-Directed RNA Polymerase;Failure;genetic information;Genetic Materials;Genetic Transcription;genome integrity;Genome Stability;Genomic Instability;Head;histone modification;Human;insight;Lead;Malignant Neoplasms;MCM Protein;Molecular Conformation;Mutation;next generation;ORC1L gene;Pathway interactions;Play;preservation;prevent;Proteins;Reaction;reconstitution;repaired;Role;segregation;System;Time;Topoisomerase;transmission process

PROJECT_TITLE: Mechanisms of DNA Replication, Chromosome Compaction, and Chromosome Unlinking

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


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

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative Our proposal exemplifies how identification of neural circuit mechanisms by which adult-born neurons contribute to memory may edify new strategies to improve social memory in aging and MCI

PI_NAMEs: SAHAY, AMAR  (contact)

PROJECT_TERMS: Adult;Affect;age related;Age-associated memory impairment;aged;Aging;aging related;aging reversal;Behavioral Paradigm;candidate validation;Cells;CHD7 gene;Chromatin;Cognitive;Communities;Coupling;Data;dentate gyrus;design;Development;Discrimination;Episodic memory;experience;Female;Frequencies;gain of function;Genetic;genetic approach;Goals;Grant;granule cell;Hippocampus;Human;Hyperactivity;Hypothalamic structure;Impairment;improved;in vivo;Interneurons;male;Maps;Mediating;Memory;memory consolidation;Memory impairment;Memory Loss;memory process;memory recognition;middle age;mild cognitive impairment;Molecular;Molecular Profiling;Mus;neural circuit;neurogenesis;neuronal excitability;Neurons;Neurosciences;nonhuman primate;novel;old mice;optogenetics;overexpression;Parvalbumins;patch clamp;Play;Prefrontal Cortex;programs;Property;Publishing;recruit;Resources;response;ribosome profiling;Rodent;Role;Route;Site;social;Testing;tool;Update;Viral

PROJECT_TITLE: Targeting neurogenesis-inhibition coupling to improve memory in aging


ED_INST_TYPE: SCHOOLS OF EDUCATION

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Pediatric;Prevention;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_CITY: LOGAN

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UTAH STATE UNIVERSITY

ORG_STATE: UT

PHR: PROJECT NARRATIVE Rooted in life course developmental theory, the proposed study examines how disruptions related to the COVID-19 pandemic are associated with immediate and longitudinal changes in adolescents' and their parents' alcohol and other substance use. Testing life course principles about developmental timing, linked lives, and cumulative disadvantage, we will specifically investigate how the timing of COVID-19 pandemic- induced disruptions, other family members' substance use patterns, and youth's personal, dispositional, and relational qualities shape teens' alcohol and other substance use trajectories over the arc of the pandemic. Understanding how adolescents and parents suffered, adapted, and coped with pandemic challenges is critical for developing responses to other public health emergencies, including economic crises and natural disasters, for anticipating long-term trends in alcohol and other substance use among the current cohort of adolescents, and for supporting recovery from this era.

PI_NAMEs: WHITEMAN, SHAWN DAVID (contact)

PROJECT_TERMS: Acceleration;Acute;Address;Adolescent;adolescent alcohol and drug use;Adult;Affect;Age;Alcohol consumption;Alcoholic beverage heavy drinker;Alcohols;Anxiety;Child;Chronic;Chronology;Cognition;cohort;Cohort Studies;Communities;Conflict (Psychology);coping;COVID-19;COVID-19 pandemic;Data;Data Analyses;Data Collection;design;Development;Developmental Course;Disadvantaged;Disease remission;Economics;Emergency Situation;Epidemiology;Equation;Essential worker;Esthesia;Event;experience;falls;Family;Family member;Family Relationship;Financial Hardship;flexibility;follow-up;Frequencies;Friends;Gender;Health;Heavy Drinking;high school;Home;Individual;Individual Differences;Institution;Interruption;Life;Life Cycle Stages;Link;longitudinal design;Longitudinal Studies;Longitudinal trends;Modeling;Mothers;Natural Disasters;novel;pandemic disease;pandemic disruption;pandemic impact;pandemic stressor;parental involvement;parental monitoring;Parents;Pattern;peer;Persons;pre-pandemic;Predisposition;Procedures;prospective;protective factors;Public Health;public health emergency;Recovery;Recovery Support;Relapse;resilience;response;Risk;Risk Factors;Role;Schools;Shapes;Siblings;Site;social disparities;Social Environment;Socialization;Stress and Coping;stressor;Structure;substance use;Surveys;Teenagers;Testing;theories;Time;underage drinking;United States;vaccine acceptance;Work;Youth

PROJECT_TITLE: Longitudinal Impacts of Pandemic-Induced Disruptions on Adolescent Siblings' and Parents' Alcohol Use: A Family Life Course Perspective


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Health Services;Hematology;Kidney Disease;Pediatric;Precision Medicine;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative Transplant-associated thrombotic microangiopathy (TA-TMA) is an often-fatal hematologic disorder without an effective treatment currently. This project aims to provide a better understanding of the epidemiology and risk factors for this rare disease and to design and test a dynamic risk prediction tool through a prospective cohort study. Results of this proposal will be helpful to the understanding of the disease and the design of future interventional trials.

PI_NAMEs: LI, ANG  (contact)

PROGRAM_OFFICER_NAME: DI FRONZO, NANCY L

PROJECT_TERMS: Acute Graft Versus Host Disease;Address;adjudication;Adult;Advisory Committees;Age;Allogenic;Alveolar;Angiopoietin-2;Aspergillosis;Benign;Bioethics;Biological Markers;Biological Specimen Banks;Biometry;Blood Vessels;Calcineurin inhibitor;career development;Child;Childhood;Chronic Kidney Failure;Clinical;Clinical Data;clinical diagnosis;clinical diagnostics;clinical epidemiology;Clinical Informatics;clinical predictors;clinical risk;Cohort Studies;college;Complement;Complement Activation;complement pathway;Complication;Data;design;Development;Development Plans;Diagnosis;diagnostic criteria;Diffuse;Disease;Dose;early detection biomarkers;Early Diagnosis;effective therapy;End stage renal failure;Endothelium;Enrollment;Environment;Enzyme-Linked Immunosorbent Assay;Epidemiologic Factors;Epidemiology;experience;follow-up;Funding;Future;genetic association;graft vs host disease;Grant;Hematological Disease;Hematology;Hematopoietic Stem Cell Transplantation;Hemolytic Anemia;Hemorrhage;Immune;Immunoassay;improved;Incidence;Infection;Informatics;Injury;Institution;Intervention Trial;Judgment;Kidney;kidney dysfunction;Laboratories;lateral flow assay;Measures;Medicine;Mentored Patient-Oriented Research Career Development Award;Mentorship;Modeling;Monitor;Morbidity - disease rate;mortality;Nested Case-Control Study;Neurologic Dysfunctions;novel;Organ;Outcome;Outcomes Research;Pathogenesis;Pathway interactions;patient oriented;Patient-Focused Outcomes;Patients;Pediatric cohort;Pediatric Hospitals;pediatric patients;Pharmaceutical Preparations;Physicians;Population Sciences;post-transplant;predictive tools;prospective;Prospective cohort;Prospective, cohort study;Qualifying;Rare Diseases;Regimen;Reporting;Research;Research Training;Retrospective cohort study;Retrospective Studies;Risk;Risk Factors;Risk Marker;risk prediction;risk stratification;Scientist;screening;Sirolimus;Source;Southwestern United States;specific biomarkers;Steroids;success;Testing;Texas;Thrombocytopenia;Thrombosis;thrombotic;Time;Toxic effect;Training;transplant centers;Transplant Recipients;Transplantation;United States;Validation;Viremia

PROJECT_TITLE: Epidemiology and Biomarkers in Transplant Associated Thrombotic Microangiopathy (TA-TMA): A Prospective Validation Cohort Study

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(JA)]


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Conditions Affecting the Embryonic and Fetal Periods;Depression;Fetal Alcohol Spectrum Disorders (FASD);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infant Mortality;Intellectual and Developmental Disabilities (IDD);Machine Learning and Artificial Intelligence;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rare Diseases;Serious Mental Illness;Sleep Research;Social Determinants of Health;Substance Misuse;Sudden Infant Death Syndrome;Tobacco;Tobacco Smoke and Health;Women's Health Research

ORG_NAME: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC

PHR: PROJECT NARRATIVE The current application is a comprehensive analysis of prenatal maternal risk factors (alcohol use, smoking, depression, and anxiety), as well as deep phenotyping of infant electrophysiological/physiological data, and associations with neurobehavioral outcomes. It will use extant data from ~11,000 participants from the Safe Passage Study and extant neurodevelopmental outcome data from a subset of participants at 12 months and 24-37 months of age. Findings will have important implications for public health by documenting the effects of prenatal maternal substance abuse and psychological health on shaping children’s cognitive and social- emotional development.

PI_NAMEs: FIFER, WILLIAM P. (contact)

PROGRAM_OFFICER_NAME: POWELL, ELIZABETH

PROJECT_TERMS: 3 year old;Address;Age;Age Months;Alcohol consumption;alcohol exposure;alcohol risk;Alcohols;antepartum depression;Anxiety;Artificial Intelligence;autism spectrum disorder;Autonomic nervous system;biomarker identification;Birth;Central Nervous System;Child;Cognitive;cognitive ability;cohort;Data;Data Analyses;Data Set;Databases;demographics;Development;Documentation;drinking;Early identification;Early Intervention;Electrocardiogram;Electroencephalography;Electrophysiology (science);Emotional;Enrollment;Ethnic Population;experience;Exposure to;fetal;Fetal Alcohol Exposure;Fetal Alcohol Spectrum Disorder;follow-up;Follow-Up Studies;Funding;Geography;Goals;Grant;health disparity;health disparity populations;health economics;improved;Infant;Infant Development;infant outcome;innovation;insight;Learning;Life;Machine Learning;maternal alcohol use;maternal anxiety;maternal depression;maternal risk;Measures;Mediating;Mediator;Medical History;Mental Depression;Mental Health;Methodology;Mission;Modified Checklist for Autism in Toddlers;Mothers;Motor Skills;National Institute on Alcohol Abuse and Alcoholism;Neonatal;nervous system development;Nervous System Physiology;neurobehavioral;neurodevelopment;neurodevelopmental effect;neurophysiology;Newborn Infant;Northern Plains;offspring;Outcome;Parents;Participant;Pattern;Perinatal;Phenotype;Physiological;Physiology;Populations at Risk;Pregnancy;prenatal;prenatal exposure;psychiatric symptom;Psychopathology;Psychosocial Factor;Public Health;racial diversity;racial population;recruit;Reporting;Research;Research Design;Research Personnel;resilience;Risk;Risk Factors;screening;secondary analysis;Shapes;signal processing;Signal Transduction;Smoking;smoking during pregnancy;smoking exposure;social;Socioeconomic Factors;Socioeconomic Status;socioeconomics;South Africa;stillbirth;Substance abuse problem;substance use;Sudden infant death syndrome;Techniques;Testing;Underrepresented Populations;United States;United States National Institutes of Health

PROJECT_TITLE: Neurodevelopmental Effects of Prenatal Exposure to Maternal Drinking, Smoking and Adverse Psychosocial Factors: Deep Phenotyping of Infant CNS and ANS Function

STUDY_SECTION: CPDD

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


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cannabinoid Research;Cardiovascular;Chronic Pain;Complementary and Integrative Health;Dietary Supplements;Heart Disease;Natural Products;Pain Research;Therapeutic Cannabinoid Research

ORG_NAME: HERBERT H. LEHMAN COLLEGE

PHR: Project Narrative There is a pressing need to find new compounds to help manage pain due to the ongoing opioid epidemic, and plants, being a source of other analgesic drugs, provide a useful starting point for discovering such compounds. Aconitum is a plant species used in traditional Chinese medicine that produces analgesic diterpenoid alkaloids, while American medicinal Aconitum species also produce diterpenoid alkaloids, but have not been explored in detail for analgesic properties. This project will analyze eight Aconitum species, specifically regarding their analgesic diterpenoid alkaloids that lack cardiotoxicity, with the goal of identifying lead compounds for future preclinical studies.

PI_NAMEs: KENNELLY, EDWARD JAMES (contact)

PROGRAM_OFFICER_NAME: CUPIT, PAULINE

PROJECT_TERMS: Aconitum;Alkaloids;American;Analgesics;Animals;Anti-Inflammatory Agents;Asia;Asian;Biological;Biological Assay;Biological Testing;Cannabidiol;cannabinoid receptor;Capsaicin;Cardiotoxicity;career development;Chemical Structure;Chemicals;Chemistry;Chinese;Chinese Traditional Medicine;Complex;Data;Discriminant Analysis;Diterpenes;drug discovery;endogenous cannabinoid system;Europe;Family;Future;Goals;graduate student;in vivo;Lead;Liquid Chromatography;Manuscripts;Medicine;metabolomics;Modeling;Modernization;Molecular;Molecular Target;Natural Products;Natural Products Chemistry;non-opioid analgesic;North America;novel;novel therapeutics;opioid epidemic;Opioid Receptor;opioid withdrawal;Opium;Outcomes Research;Pain;Pain management;Pattern;Pharmaceutical Preparations;Pharmacopoeias;Physicians;Phytochemical;Plant Extracts;Plants;preclinical study;Property;Public Health;Ranunculaceae;Reporting;Research;response;Safety;Salicylic Acids;scaffold;Source;Structure;symposium;System;tandem mass spectrometry;Techniques;Technology;Testing;Therapeutic;Therapeutic Uses;time of flight mass spectrometry;tool;Traditional Medicine;Training;undergraduate student;Underrepresented Populations;United States National Institutes of Health;Variant;Zebrafish

PROJECT_TITLE: Discovery of analgesic diterpenoid alkaloids from medicinal Aconitum plants using a metabolomic approach


ORG_CITY: DURHAM

ORG_DEPT: PHARMACOLOGY

ORG_NAME: DUKE UNIVERSITY

PHR: The proposal aims to characterize the regulation of LRRK2 during lysosome stress response and its importance in neurodegeneration.

PI_NAMEs: YAO, TSO-PANG  (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TITLE: Regulation of LRRK2 in lysosomal stress response

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Congenital Structural Anomalies;Kidney Disease;Pediatric;Polycystic Kidney Disease

ORG_CITY: DETROIT

ORG_DEPT: PHYSIOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE The autosomal dominant polycystic kidney disease (ADPKD) which is the fourth leading cause of kidney failure is characterized by development of multiple cysts, hollow sacks containing liquid, which replace normal tissues and lead to kidney failure. Growing evidence suggests that high ATP level in the cysts is involved in PKD progression but the origins and pathogenic effects of the ATP accumulation in cysts remains unknown. If funded, the proposed project would contribute to fundamental knowledge and provide a strong evidential base for targeting purinergic signaling in ADPKD treatment.

PI_NAMEs: PAVLOV, TENGIS S (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Ablation;absorption;Adenosine;Affect;Aging;Aldosterone;Autosomal Dominant Polycystic Kidney;Autosomal Recessive Polycystic Kidney;base;Breeding;Calcium;Calcium Signaling;Cell Culture Techniques;Cell Line;Cell membrane;Clinical;Clinical Research;Complex;Cyst;Cyst Fluid;Cystic kidney;Data;design;Development;Disease Progression;Duct (organ) structure;Electrolytes;epithelial Na+ channel;Epithelium;Excretory function;Exhibits;Experimental Models;experimental study;Funding;Genetic;Genetic Predisposition to Disease;Gout;Growth;Human;Image;Impairment;improved;in vivo;Inherited;inorganic phosphate;Integral Membrane Protein;Intervention;Ion Transport;Kidney Diseases;Kidney Failure;Knock-out;Knockout Mice;Knowledge;Liquid substance;Live Birth;Mammalian Cell;Measurement;Mediating;Membrane;Modeling;Molecular Conformation;Monitor;monolayer;mouse model;Mus;Nephrons;Normal tissue morphology;P2X-receptor;paracrine;patch clamp;Pathogenicity;Pathologic;Patients;Permeability;pharmacologic;Polycystic Kidney Diseases;prevent;Probenecid;Process;promoter;Protein Family;Proteins;Publishing;Purinoceptor;Rattus;receptor;Regulation;Renal function;Reporting;Rodent Model;Role;Signal Transduction;Sodium;Stimulus;Study models;System;Testing;Water

PROJECT_TITLE: Pannexin-1/P2X7 interaction promotes excessive ATP release in kidney cysts and ADPKD progression via reduced NaCl reabsorption

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-P(03)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Machine Learning and Artificial Intelligence;Mental Health;Neurosciences

ORG_CITY: GAINESVILLE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative Social behavior deficits are key features of many psychiatric disorders, yet little is known about how the brain controls normal social behaviors. I propose to dissect the role of the medial prefrontal cortex circuits in social dominance by combining wireless electrophysiology, calcium imaging, optogenetics and machine learning. This study will broaden our understanding of how neural circuits control normal social behaviors and will contribute to the identification of novel interventions for social deficits.

PI_NAMEs: PADILLA COREANO, NANCY  (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Affect;Agonistic Behavior;Animals;Behavior;Behavioral;Behavioral Assay;Bilateral;Biological Assay;brain control;Calcium;cell cortex;Cells;Data;Dissection;Electrophysiology (science);Food;Frequencies;Glutamates;Goals;Hippocampus;Human;Hypothalamic structure;Image;in vivo;in vivo imaging;Individual;Investigation;Knowledge;Lateral;Literature;Machine Learning;Measurement;Medial;Memory;Mental disorders;Mentors;Methods;Modeling;Motivation;Mus;neural;neural circuit;neural correlate;nonhuman primate;novel;novel strategies;Opsin;Optics;optogenetics;Output;Partner in relationship;Pathway Analysis;Phase;Play;Prefrontal Cortex;Probability;programs;recruit;redshift;Research;resilience;Resources;Rewards;Rodent;Role;Signal Transduction;Site;social;Social Behavior;social competition;social deficits;Social Dominance;Social Environment;social influence;Social Interaction;social interventions;social neuroscience;Stress;Structure;Techniques;Testing;Therapeutic;Time;tool;Training;training opportunity;Tube;unsupervised clustering;unsupervised learning;wireless

PROJECT_TITLE: Studying how the hippocampal-prefrontal-hypothalamic circuit encodes social dominance

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Pediatric;Primary Immunodeficiencies;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative  Discovering the genetic and molecular basis of monogenic inborn errors of immunity is an important scientific goal because it helps patients with rare and often neglected diseases while also providing fundamental insights that apply more broadly to prevalent human diseases. The goal of this proposal is to elucidate the cellular, molecular, and immunological mechanisms underlying a novel autoinflammatory disease we discovered is caused by a monogenic transcription factor defect.

PI_NAMEs: LUCAS, CARRIE L. (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Affect;Age;anakinra;antagonist;Anti-Inflammatory Agents;antiviral immunity;autoinflammation;autoinflammatory;autoinflammatory diseases;Automobile Driving;Biochemical;Biological Assay;Biology;Biopsy;CD3 Antigens;CD8B1 gene;Cell Differentiation process;Cell model;cell type;Cells;Childhood;congenital immunodeficiency;constitutive expression;CXCL1 gene;Data;Defect;Development;Disease;disease model;DNA Binding;DNA Binding Domain;early onset;Epithelial Cells;Etiology;Evolution;Exhibits;Experimental Autoimmune Encephalomyelitis;Feces;Fever;fitness;gain of function;Gene Expression;Gene Targeting;Genes;Genetic;Genetic Transcription;Genomics;Goals;Hematopoietic System;Homing;Homodimerization;Housekeeping Gene;Human;human disease;Human Genetics;human genomics;IL17 gene;IL18 gene;IL1R1 gene;Immune;immune activation;immune function;Immune System Diseases;Immunofluorescence Immunologic;Immunologics;Immunology;immunopathology;immunoregulation;In Situ;in vivo;Inflammasome;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory marker;Inflammatory Response;Injury;insight;Interferon Type I;Interferons;Interleukin-1;Interleukin-10;Investigation;Knock-out;Knockout Mice;Knowledge;Leukocyte L1 Antigen Complex;Life;Link;loss of function;loss of function mutation;LoxP-flanked allele;Macrophage;male;Measures;Mediating;Mediator;Methods;Microbe;microbial;Modeling;Molecular;molecular modeling;mouse model;Mouse Strains;mRNA Decay;Mucositis;Mucous Membrane;Mus;mutant;Mutant Strains Mice;Mutation;Myelogenous;Myeloid Cells;Names;Natural Killer Cells;neglect;Nonsense-Mediated Decay;novel;Nucleotides;old mice;Oral Ulcer;pathogen;Pathology;Pathway interactions;Patients;Phenotype;Physiological;Post-Translational Protein Processing;Production;programs;Proliferating;Proteins;Publishing;receptor;Regulation;Reporter Genes;Reporting;response;Role;Serum;Shapes;Signal Transduction;Sodium Dextran Sulfate;Stains;STAT1 gene;STAT3 gene;Surface;targeted treatment;Therapeutic;Time;Tissues;transcription factor;Tryptophan;Variant;Work

PROJECT_TITLE: Mechanisms of mucosal autoinflammation elucidated by a novel monogenic transcription factor defect

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Digestive Diseases;Immunotherapy;Nanotechnology;Orphan Drug;Pancreatic Cancer;Rare Diseases

PHR: Narrative: This application will develop a new combination therapy for the treatment of pancreatic cancer that lacks effective treatments.

PI_NAMEs: LI, SONG  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: Abraxane;Adjuvant Therapy;Albumins;antagonist;anti-PD1 therapy;Binding;Biodistribution;Biological;Biological Availability;Biophysics;Blood;Blood Circulation;Breast Cancer Model;Cancer Etiology;cancer type;CCL2 gene;CCL7 gene;CD8-Positive T-Lymphocytes;Cells;Cessation of life;chemotherapy;Circulation;Clinic;Colon Carcinoma;Combined Modality Therapy;Complex;Cytidine Deaminase;Data;Deaminase;Death Rate;design;Development;Diagnosis;Doxorubicin;Doxorubicin Hydrochloride Liposome;Drug vehicle;Early Diagnosis;effective therapy;Extravasation;gemcitabine;Human;hydrophilicity;Hydrophobicity;Immune;improved;In Vitro;in vivo;Incidence;Malignant neoplasm of pancreas;Malignant Neoplasms;Metabolic;Modeling;Mus;Myeloid-derived suppressor cells;Names;nanocarrier;nanomedicine;nanoparticle;nanosized;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;new combination therapies;novel therapeutics;Paclitaxel;pancreatic cancer model;pancreatic ductal adenocarcinoma model;Particle Size;patient derived xenograft model;Patients;Penetration;Pharmaceutical Preparations;Polymers;preclinical study;Probability;Prodrugs;Property;recruit;Recurrence;Regimen;Resectable;Survival Rate;T cell response;Time;Toxic effect;Treatment Efficacy;tumor;Tumor Cell Invasion;Tumor Promotion;Tumor Tissue;tumor-immune system interactions;United States;Up-Regulation

PROJECT_TITLE: Combination Therapy for Pancreatic Cancer

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Childhood Leukemia;Clinical Research;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Acute Myeloid Leukemia (AML) is a deadly hematologic malignancy that results from the progressive acquisition of mutations over time. Mutations in the hematopoietic transcription factor CEBPA must precede mutations in the cytokine receptor CSF3R in order for leukemia to develop. This proposal seeks to understand the mechanism of this order dependent leukemia development and leverage this understanding to develop novel therapeutics.

PI_NAMEs: BRAUN, THEODORE PAUL (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;Area;Bioinformatics;Biological Assay;Bone Marrow;Bone Marrow Cells;CCAAT-Enhancer-Binding Protein-alpha;Cells;ChIP-seq;Chromatin;Clonal Evolution;Committee Members;core binding factor alpha;Core-Binding Factor;Cytokine Receptors;cytotoxicity;Data;Dedications;Dependence;Development;Disease;DNA Binding;driver mutation;Enhancers;Epigenetic Process;epigenetic profiling;epigenetic therapy;epigenome;experimental study;Flow Cytometry;FLT3 gene;Functional disorder;gene therapy;Goals;Grant;Granulocyte Colony-Stimulating Factor Receptors;Hematologic Neoplasms;Hematopoietic;Hematopoietic stem cells;Human;In Vitro;in vivo;Individual;inhibitor;KDM1A gene;knock-down;Laboratories;leukemia;loss of function;Lysine;Malignant - descriptor;Malignant Neoplasms;Mentors;Mentorship;Modeling;Mus;mutant;Mutation;Myelogenous;Myeloproliferative disease;MYH11 gene;novel;novel therapeutic intervention;novel therapeutics;Outpatients;overexpression;Participant;Patients;Phenotype;prevent;Process;Property;receptor;recruit;Research;Research Personnel;Role;Running;Sampling;Signal Pathway;Signal Transduction;small hairpin RNA;Sum;synergism;System;t(8;21)(q22;q22);targeted agent;targeted cancer therapy;targeted treatment;Therapeutic;Therapeutic Intervention;Time;Training;transcription factor;transcriptome sequencing;Work

PROJECT_TITLE: Epigenetics of Mutation-Order in Acute Myeloid Leukemia


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

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative: High levels of cholesterol are linked to many chronic diseases including heart disease, type II diabetes and fatty liver disease. We have generated novel mouse models where cells in the body have lost the ability to respond to changes in cholesterol. When fed a high cholesterol diet these mice rapidly develop liver disease and will provide a new model system to study how cholesterol influences many chronic diseases.

PI_NAMEs: SCHULMAN, IRA G (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Adult;Affect;Agonist;Binding;Biological Models;Cardiovascular Diseases;Cell model;cell type;Cells;Cholesterol;Cholesterol Homeostasis;Chronic Disease;chronic liver disease;Cirrhosis;Collagen;Coupled;Deposition;Diet;Dominant-Negative Mutation;Enterobacteria phage P1 Cre recombinase;Event;experimental study;Fatty acid glycerol esters;Fatty Acids;fatty liver disease;Fibrosis;Gene Expression;Genes;Genetic;Genetic Transcription;Heart Diseases;Hepatic;Hepatic Stellate Cell;Hepatocyte;Heterozygote;Human;Immune;immune cell infiltrate;Impairment;Individual;Inflammation;Inflammatory;insight;Ligands;Link;lipid metabolism;Liver;Liver diseases;Liver Failure;liver inflammation;LXRalpha protein;mouse model;Mus;Mutation;Myeloid Cells;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;overexpression;Pathogenesis;Pathologic;Pathology;Patients;pharmacologic;Phenotype;Phenylalanine;Population;Primary carcinoma of the liver cells;Process;response;Risk;Role;selective expression;sensor;Severity of illness;Signal Transduction;single-cell RNA sequencing;Testing;Time;Tissues;tool;Transcriptional Activation;Transcriptional Coactivator with PDZ-Binding Motif;Transcriptional Regulation;Triglycerides;Tryptophan;United States

PROJECT_TITLE: LXR-Dependent Cholesterol Sensing

STUDY_SECTION: CSME

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


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Rare Diseases;Social Determinants of Health;Vector-Borne Diseases

ORG_CITY: Framingham

ORG_NAME: KEPHERA DIAGNOSTICS, LLC

PHR: Project Narrative This project addresses the critical need for an accurate rapid, point-of-care test for Chagas disease. This parasitic infection has emerged as a threat to public health and the blood supply both within the U.S. and internationally, yet only one FDA-cleared, commercial rapid test for Chagas disease is currently available. In Phase II, we propose to complete development of a Chagas disease lateral flow rapid test based on native antigens of the parasite. We will carry out a clinical study to support a 510(k) submission to FDA, and achieve clearance of the Chagas point-of-care test for in vitro diagnosis of infected individuals.

PI_NAMEs: LEVIN, ANDREW E. (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Acceleration;Acute;Address;Algorithms;anti-IgG;Antibodies;antigen detection;Antigen-Antibody Complex;Antigenic Diversity;Antigenic Variation;Antigens;Archives;Area;assay development;Binding;Biological Assay;Biotinylation;Blood;Blood Transfusion;Blood-Borne Pathogens;Cardiomyopathies;Caring;Central America;Central American;Chagas Disease;chronic infection;Clinical;Clinical Research;Clinical Sensitivity;cost effective;Country;cross reactivity;design;detection sensitivity;Development;Devices;Diagnosis;Diagnostic;diagnostic development;Diagnostic tests;Disadvantaged;Epidemiologic Monitoring;Excretory function;FDA approved;Filtration;Generations;Genotype;Geography;Gold Colloid;Harvest;Health;health inequalities;Hepatitis C virus;HIV;Human;Immigrant;Immigrant community;Immigration;Immunoassay;Improve Access;in vitro testing;Individual;Infection;Infrastructure;innovation;Insect Vectors;International;Laboratories;Lateral;lateral flow assay;Latin America;Latin American;Leishmania;Life;manufacture;manufacturing scale-up;manufacturing test;Medical;Membrane;Methods;Mexican Americans;Mexico;Morbidity - disease rate;mortality;Organ Transplantation;Outcome;Parasites;Parasitic Diseases;Parasitic infection;Pathologic;Patients;Performance;performance tests;Phase;phase 1 study;point of care;point of care testing;point-of-care diagnostics;Population;Populations at Risk;Procedures;Production;prospective;Proteins;prototype;Public Health;rapid test;Readiness;Reagent;Recombinants;Resource-limited setting;Resources;Risk;Rural;Sampling;Sensitivity and Specificity;Serology;Serology test;Serum;Site;South America;Streptavidin;Study models;success;System;Temperature;Testing;Time;tool;transmission process;Trypanosoma;Trypanosoma cruzi;Validation;Vascular blood supply

PROJECT_TITLE: Point-of-care diagnostic test for T. cruzi (Chagas) infection


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Infectious Diseases;Malaria;Malaria Vaccine;Orphan Drug;Prevention;Rare Diseases;Social Determinants of Health;Vaccine Related;Vector-Borne Diseases

ORG_CITY: LEIDEN

ORG_COUNTRY: NETHERLANDS

ORG_FIPS: NL

ORG_NAME: LEIDEN UNIVERSITY MEDICAL CENTER

PHR: PROJECT NARRATIVE Reports on resurgence in Plasmodium falciparum malaria cases, after years of control, indicates that a highly efficacious vaccine is needed, yet, promising malaria vaccines first tested in high income countries, show disappointing results in endemic areas. Our multi-omics technologies that has uncovered the importance of baseline immunological profiles to predict vaccine induced and naturally acquired immunity, will be applied to malaria vaccine cohorts from diverse geographical areas to understand malaria vaccine (hypo)responsiveness. The knowledge will build a strong foundation for developing an improved malaria vaccine with high efficacy in malaria endemic areas.

PI_NAMEs: YAZDANBAKHSH, MARIA  (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: acquired immunity;Address;Adjuvant;Affect;Africa;African;American;Antibodies;Antigen Presentation;Area;Attenuated;B-Lymphocytes;Bayesian Modeling;Biological;Biological Assay;Cell Physiology;Cells;Chemoprophylaxis;clinical development;clinically relevant;cohort;Complement;Country;Cytometry;Data;Data Analytics;Data Engineering;data integration;data management;Disease;Dose;Ebola;Environmental Exposure;Environmental Risk Factor;Erythrocytes;Europe;European;evidence base;experimental study;Exposure to;Falciparum Malaria;Foundations;Gabon;Genetic;Genetic Determinism;Geographic Locations;global health;glycosylated IgG;Hepatocyte;high dimensionality;Human;Immune;immune activation;Immune response;Immune system;Immunity;immunogenicity;Immunologics;immunoregulation;improved;Income;Individual;Infection prevention;Inflammation;Influenza;influenza virus vaccine;innovation;insight;Integration Host Factors;Knowledge;Link;Liver;low and middle-income countries;Lymphocyte;Malaria;Malaria Vaccines;Measures;Mediation;Metabolic;Methodology;microorganism;Molecular;multiple omics;Myelogenous;Nature;North America;Outcome;Parasites;Pathway interactions;Phenotype;Plasmodium falciparum;Plasmodium falciparum vaccine;Play;Population;Process;Public Health;Recording of previous events;Regimen;Reporting;Research;response;Role;Rural;rural area;Safety;Sampling;Secure;Shapes;Sporozoites;Subunit Vaccines;T-Lymphocyte;Technology;Testing;Tetanus Vaccine;Time;Tissues;transcriptome sequencing;transcriptomics;urban area;Vaccination;vaccine efficacy;vaccine response;vaccine trial;vaccine-induced immunity;Vaccines;Variant;Whole Organism;Yellow Fever

PROJECT_TITLE: Baseline host and environmental factors that impact pre-erythrocytic malaria vaccine (hypo)responsiveness in endemic regions


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Skin Cancer

ORG_DEPT: SURGERY

PHR: PUBLIC HEALTH RELEVANCE STATEMENT Melanoma is a skin cancer that can be aggressive when it recurs or spreads. This study will explore the modified poliovirus (PVSRIPO) for treatment of advanced melanoma. The studies in the proposal will examine data in human melanoma tumor cells, an animal model of melanoma, and a small human clinical trial of PVSRIPO injected into melanoma tumors.

PI_NAMEs: BEASLEY, GEORGIA  (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: adaptive immune response;Aftercare;age group;Animal Model;antagonist;anti-tumor immune response;Antineoplastic Agents;Antitumor Response;Attenuated;Award;Biopsy;Blood;career;career development;Cell Line;Cells;Cessation of life;Clinical;clinical practice;Clinical Trials;Combined Modality Therapy;cytotoxic;cytotoxicity;Data;Dedications;Dendritic Cells;Development;Disease;disease diagnosis;Disease Progression;Doctor of Philosophy;effective therapy;efficacy evaluation;experience;experimental study;Gene Modified;Genes;Glioblastoma;Goals;Human;Human poliovirus;Immune;immune activation;Immune checkpoint inhibitor;Immunocompetent;immunogenic;Immunologics;Immunologist;Immunology;improved;In Vitro;in vivo;Incidence;Infection;Inflammation;Inflammatory;Innate Immune Response;Innate Immune System;Interferon Type II;Interferons;Laboratories;Macrophage;Malignant Neoplasms;Mediating;Melanoma;Melanoma Cell;Melanoma patient;Melanoma Tumor;Mentors;Metastatic Melanoma;Modeling;mouse model;Mus;neoplastic cell;neurovirulence;novel;novel therapeutics;Oncolytic;oncolytic virotherapy;Operative Surgical Procedures;Patient Care;patient prognosis;Patients;PD-L1 blockade;Phase I Clinical Trials;phase I trial;Physicians;Poliovirus Vaccines;Positioning Attribute;pre-clinical;Principal Investigator;professor;Program Development;programmed cell death ligand 1;programmed cell death protein 1;Proteins;public health relevance;Publishing;Recurrence;Research;research and development;Resistance;Resistance development;Risk;Scientist;Serotyping;skills;Skin Cancer;Skin Malignancy;Specimen;stem;Surgeon;Testing;Therapeutic;Time;tool;Toxic effect;Translating;Translations;Treatment Failure;tumor;tumor growth;Tumor Immunity;tumor microenvironment;Tumor Tissue;United States;Universities;Viral;Virus Activation;Work;young adult

PROJECT_TITLE: PVSRIPO in melanoma


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Immunotherapy;Neurosciences;Orphan Drug;Patient Safety;Pediatric;Pediatric Cancer;Radiation Oncology;Rare Diseases

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: PBTC Project Narrative The Pediatric Brain Tumor Consortium (PBTC) conducts novel and innovative clinical trials for Pediatric Central Nervous System (CNS) malignancies that incorporate correlative biology, genomics, pharmacology and sophisticated imaging techniques to advance the understanding of high-risk and recurrent pediatric brain tumors. PBTC trials are designed to define appropriate dosing, describe pediatric-specific toxicities and tumor biology as well as to identify early signals of efficacy, thereby directly impacting future prognostication and treatment strategies. It is only through this continued prospective and systematic drug development via early phase clinical trials that the overarching goal of achieving longer, healthier lives with less morbidity can ultimately be realized for children with CNS tumors.

PI_NAMEs: DUNKEL, IRA J;ONAR-THOMAS, ARZU  (contact)

PROGRAM_OFFICER_NAME: SMITH, MALCOLM M

PROJECT_TERMS: Adult;Adverse event;anti-cancer research;appropriate dose;Area;Basic Science;Biological;Biology;Biometry;Biotechnology;BRAF gene;Brain Neoplasms;Cancer Therapy Evaluation Program;Cancer Vaccines;Central Nervous System;Central Nervous System Neoplasms;Cessation of life;Child;Childhood;Childhood Brain Neoplasm;Childhood Central Nervous System Neoplasm;Clinical;Clinical Trials;Collaborations;Contracts;Convection;data acquisition;data management;data submission;Development;Diffuse intrinsic pontine glioma;drug development;Early identification;early phase clinical trial;Electronics;Eligibility Determination;Ependymoma;epigenomics;experience;Focused Ultrasound;Future;Genomics;Geography;Glioma;Goals;high risk;Image;Imaging Techniques;Immune checkpoint inhibitor;Immunologics;Immunotherapeutic agent;Immunotherapy;improved;infant embryonal tumors;innovation;Institution;Intervention;Intrinsic factor;Laboratories;Laboratory Study;Local Therapy;Magnetic Resonance Imaging;Malignant Neoplasms;MAP Kinase Gene;Measures;Mediation;Medulloblastoma;member;Mission;Modality;Molecular Target;Monitor;Morbidity - disease rate;mortality;multidisciplinary;Mutation;National Cancer Institute;neuroimaging;neuropathology;Neurosurgeon;novel;novel strategies;Oncolytic viruses;operation;Pathway interactions;Pediatric Brain Tumor Consortium;Pediatric Neoplasm;Pediatric Oncology Group;pediatric patients;Pediatrics;Persons;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Pharmacologic Substance;Pharmacology;Phase;phase 2 study;Prognostic Factor;prognostication;programs;prospective;protocol development;quality assurance;Quality of life;Radiation Oncologist;Radiation Oncology;Recurrence;Refractory;Research;research clinical testing;Research Design;Research Personnel;response;Safety;Saint Jude Children's Research Hospital;Science;Series;Signal Transduction;Site;Solid Neoplasm;Structure;success;survival outcome;System;targeted agent;Therapeutic;Tissues;Toxic effect;Translating;Translational Research;translational scientist;Translational trial;Treatment Failure;treatment response;treatment strategy;trial design;tumor;Tumor Biology;tumor diagnosis;working group

PROJECT_TITLE: Pediatric Brain Tumor ConsortiumA multi-institutional consortium devoted to novel phase I and II clinical evaluations of experimental treatment approaches for pediatric CNS tumors.


ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Narrative This proposal is focused on examining the role of surface sensing in Pseudomonas aeruginosa biofilm formation and pathogenesis as it relates to chronic infection. The expression of several key biofilm matrix components are known to be initiated upon interaction with a surface. This proposal will address gaps in our knowledge as to how surface sensing works and its contribution to pathogenesis; future therapeutic strategies (particularly ones directed towards biofilm communities) will benefit from such knowledge.

PI_NAMEs: PARSEK, MATTHEW R. (contact);WOZNIAK, DANIEL J

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: antimicrobial;Bacteria;Bacterial Adhesins;cell envelope;Cells;Chronic;chronic infection;Clinical;Coculture Techniques;Cystic Fibrosis;Data;Elements;Environmental Risk Factor;Event;experimental study;fitness;Future;Gene Cluster;genetic approach;Genotype;Goals;Growth;Human;Immunology procedure;In Vitro;Infection;Knowledge;Link;Membrane;Microbial Biofilms;Morbidity - disease rate;mortality;mouse model;Mus;Mutagenesis;mutant;Mutation;Natural Immunity;neutrophil;Pathogenesis;Pathogenicity;Persons;polymicrobial biofilm;Predisposition;Production;Proteins;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Role;sensor;Signal Transduction;Stimulus;Stress;Structure;Surface;Surveys;Swimming;System;Testing;Therapeutic;transposon sequencing;Work;Wound models

PROJECT_TITLE: The pel exopolysaccharide gene cluster of Pseudomonas aeruginosa

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


ADMINISTERING_IC: HD

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

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative This proposal is submitted in response to RFA-HD-18-011, Child Health Research Career Development Award (CHRCDA) Program to provide K12 awards through the CHRCDA mechanism to young pediatric basic science investigators. This program is an investment in the future of children's health, as the diverse group of researchers we will train will harness advanced research strategies to address urgent problems (e.g., asthma, cancer, infectious diseases, host defense defects, diabetes, obesity, and developmental malformations of the heart, brain, and other organs), that will result in new treatments to improve child health outcomes.

PI_NAMEs: HIRSCH, RAPHAEL  (contact)

PROGRAM_OFFICER_NAME: WINER, KAREN

PROJECT_TERMS: Academic Training;Academy;Address;Adult;American;Arts;Basic Science;Cardiopulmonary;career;career development;Child;Child Health;Childhood;Clinical;Communities;Computational Science;design;Developmental Biology;Diagnosis;didactic education;Discipline;Doctor of Philosophy;Environment;experience;Faculty;Fostering;Future;Genetic;Health;Immunology;improved;Infrastructure;Institute of Medicine (U.S.);Investments;K-Series Research Career Programs;Laboratory Research;Laboratory Scientists;Malignant Neoplasms;Medical;Medicine;member;Mentored Clinical Scientist Development Program;Mentors;Neurobiology;next generation;pediatric department;pediatrician;Pediatrics;Prevention;Productivity;Program Development;programs;Request for Applications;Research;Research Personnel;Research Project Grants;Resources;response;Scholarship;Science;stem cell biology;Structure;Training;Training Programs;Vision;Work

PROJECT_TITLE: The Child Health Research Career Development Program at UCSF


NIH_SPENDING_CATS: Cancer;Clinical Research;Genetics;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Ovarian cancer remains the most deadly gynecological malignancy facing women, with a 5-year survival rate of less than 28% for advanced stage patients with marked peritoneal metastatic spread. For successful metastasis to occur, tumor cells must adapt to survive anchorage independence in the hostile environment of the peritoneal cavity. Our work focuses on novel mitochondrial signaling pathways that regulate cell survival adaptations during ovarian cancer metastasis and will delineate if these can be exploited to therapeutically target metastatic ovarian cancer.

PI_NAMEs: HEMPEL, NADINE  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Address;AKT inhibition;Anoikis;antioxidant enzyme;Ascites;Biochemical;cancer cell;Cell Adhesion;Cell Culture Techniques;Cell Line;Cell Survival;Cells;clinically relevant;clinically significant;cytotoxicity;Data;Deacetylase;Environment;Epigenetic Process;epigenetic regulation;Future;Genetic Transcription;Glutamine;Goals;Greater sac of peritoneum;Homeostasis;Hydrogen Peroxide;imaging approach;Imaging Techniques;improved;in vivo;inhibitor;intraperitoneal;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mediator;Metabolic;Metabolism;Metastatic Malignant Neoplasm to the Ovary;Methylation;Mitochondria;Mitochondrial Proteins;Modeling;Molecular;Monitor;Mus;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutics;Nutrient;Ovarian Clear Cell Tumor;Oxidants;oxidation;Oxidation-Reduction;Oxidative Phosphorylation;Pathway interactions;Patient-Focused Outcomes;Patients;Peritoneal;Phosphoric Monoester Hydrolases;Play;preservation;promoter;Proteins;PTEN gene;Regulation;Reporting;Resistance;response;Role;sensor;Signal Pathway;Signal Transduction;SOD2 gene;spatiotemporal;Specimen;spheroids;Stress;Stress and Coping;Superoxide Dismutase;Superoxides;Survival Rate;Testing;Therapeutic Intervention;therapeutic target;transcription factor;Transcriptional Regulation;transcriptome sequencing;tumor;Up-Regulation;Woman;Work;Xenograft Model

PROJECT_TITLE: Regulation of mitochondrial redox homeostasis and signaling in metastatic ovarian cancer

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


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

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Glial cells were long considered to serve merely in a supportive role for neuronal cell function. Recent evidence, however, indicates that glial cells are intimately involved in many of the brain's functions, including memory formation. The goal of this project is to understand a key epigenetic mechanism that contributes to gene transcription in astrocytes while considering the potential of manipulating this process to increase resiliency in aging populations including Alzheimer’s disease.

PI_NAMEs: LUBIN, FARAH DOMINIQUE (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: adenovirus mediated delivery;Adult;Age;age related;age related changes;Age-associated memory impairment;age-related disease;aged;Aging;aging brain;aging hippocampus;aging population;aging related;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Animal Model;animal old age;Animals;Area;Astrocytes;awake;behavior measurement;Biological Models;Brain;Calcium Signaling;Cell Physiology;Cells;Chromatin;chromatin isolation by RNA purification sequencing;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;CRISPR-mediated transcriptional activation;Data;density;designer receptors exclusively activated by designer drugs;DNA;DNA Methylation;Dorsal;Epigenetic Process;G9a histone methyltransferase;Gene Expression;Gene Expression Profile;Genes;Genetic;Genetic Transcription;Goals;Head;Hippocampus;histone methylation;histone modification;Human;Hypermethylation;insight;Intervention;J20 mouse;juvenile animal;knock-down;Knock-out;LoxP-flanked allele;Mediating;Memory;Memory impairment;Memory Loss;Molecular;Mus;Neuroglia;Neurons;normal aging;novel;old mice;overexpression;Pathogenesis;Pilot Projects;Play;Population;Positioning Attribute;Process;programs;promote resilience;promoter;Proteins;Regulation;Regulator Genes;Research;research study;resilience;RNA;Role;Signal Transduction;single nucleus RNA-sequencing;small hairpin RNA;System;Testing;Therapeutic;Tissue-Specific Gene Expression;transcription factor;transcriptome sequencing;Untranslated RNA;Vertebral column;Western Blotting;Work;young adult

PROJECT_TITLE: Long Non-coding RNA Regulation in Astrocytes within the Aging Brain


NIH_SPENDING_CATS: Congenital Structural Anomalies;Genetics;Kidney Disease;Pediatric;Polycystic Kidney Disease

ORG_CITY: TOLEDO

ORG_NAME: UNIVERSITY OF TOLEDO

ORG_STATE: OH

PHR: Public Health Relevance Mutations in the polycystin genes lead to one of the most common human genetic disorders, Autosomal Dominant Polycystic Kidney Disease. However, little is known about the cellular function of polycystins in cell proliferation. Here we propose to uncover the molecular role and the regulation of polycystin during the last stage of cell division cytokinesis using the model organism fission yeast.

PI_NAMEs: CHEN, QIAN  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Actin-Binding Protein;Actins;Actomyosin;Autosomal Dominant Polycystic Kidney;autosome;Biomass;Calcineurin;Calcium;Calcium Signaling;Calcium Spikes;Calmodulin;Cell Cycle;Cell division;cell growth;Cell membrane;Cell Physiology;Cell Proliferation;Cell Separation;Cell Size;Cells;Collaborations;constriction;Cytokinesis;Cytoskeleton;daughter cell;driving force;Endocytosis;Environment;Evolution;Family;Fission Yeast;Genes;Genetic Diseases;Genetic Screening;Growth;Human;Human Genetics;Image;imaging modality;In Vitro;innovation;Intracellular Transport;Ion Channel;Ions;Kidney Diseases;Lead;Lipids;loss of function mutation;mechanical force;mechanical signal;mechanotransduction;Mediating;Michigan;Microfilaments;Microfluidics;model organism;Modeling;Molecular;Morphogenesis;multidisciplinary;Mutation;Myosin Type I;Myosin Type V;novel;Osmosis;Osmotic Pressure;patch clamp;Pathway interactions;Pattern;Permeability;permissiveness;Phosphotransferases;Play;Polycystic Kidney Diseases;Process;public health relevance;Quantitative Microscopy;reconstitution;Regulation;Regulation of Cell Size;Reproducibility;response;Role;Signal Pathway;Signaling Molecule;Stimulus;Structure;synergism;Techniques;Tennessee;Testing;Universities;Work;Yeasts

PROJECT_TITLE: The mechanism of cell size regulation by polycystins

STUDY_SECTION: NCSD

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


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

ORG_CITY: IRVINE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative  Alzheimer's disease (AD) is an escalating age-related major health concern in the US. The proposed research will examine the molecular changes that occur in the course of AD using mouse models that mimic this neurodegenerative condition. The results could lead to new biomarkers for early detection of AD and candidate drug targets for development of effective treatments.

PI_NAMEs: REN, BING ;XU, XIANGMIN  (contact)

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: Affect;Age;age related;Alzheimer disease detection;Alzheimer's Disease;Alzheimer's disease model;American;Amyloid Beta A4 Precursor Protein;Amyloid beta-Protein;Animals;Architecture;ATAC-seq;Atlases;Back;Behavior;behavior change;Behavior Therapy;Behavioral;brain health;brain tissue;Cell Nucleus;cell type;Cells;Chromatin;Chromosomes;Coupled;Data;Defect;Dementia;design;Development;diagnostic tool;Disease;Disease Progression;DNA mapping;DNA Methylation;DNA methylation profiling;Dominant-Negative Mutation;drug candidate;Drug Targeting;early detection biomarkers;effective therapy;epigenome;epigenomics;exercise intervention;Exhibits;Gene Expression;Gene Expression Profile;Genes;Genetic Transcription;Goals;HDAC3 gene;Health;Hippocampus;Histone Deacetylase Inhibitor;histone modification;Human;imaging approach;Impaired cognition;Impairment;improved;in vivo calcium imaging;inhibitor;intervention effect;Joints;Knock-in;Learning;Location;Maps;Measures;Memory;Memory Loss;middle age;Modeling;Molecular;molecular marker;mouse model;multiple omics;Mus;mutant;Nerve Degeneration;neural;neural circuit;Neurodegenerative Disorders;Neurons;neuropathology;neuroregulation;new therapeutic target;novel therapeutic intervention;older adult;optogenetics;Pathogenesis;Pathway interactions;Performance;Physical Exercise;Physiology;Population;programs;Publishing;Research;response;Running;sedentary;Shapes;single cell genomics;single nucleus RNA-sequencing;targeted biomarker;Technology;Testing;transcriptome;transcriptome sequencing;Untranslated RNA;Wild Type Mouse;Work

PROJECT_TITLE: Epigenomic analysis of neural circuits in Alzheimer's disease mouse models

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: Bioengineering;Breast Cancer;Cancer;Women's Health Research

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: The majority of breast cancer deaths result from metastatic disease. Accumulated evidence indicates that breast tumor cells invade as complex, heterogeneous clusters rather than single cells and to do so they are led by cells called leader cells. How these leader cells develop to lead directed collective migration, and whether this phenomenon is necessary and sufficient to effect directed collective migration is largely unknown. This is a focus of the current proposal.

PI_NAMEs: LONGMORE, GREGORY D. (contact);PATHAK, AMIT

PROJECT_TERMS: 3-Dimensional;Adhesions;Affect;Basement membrane;Biological Process;biomechanical engineering;Biomedical Engineering;Biophysics;Blood Vessels;Breast Cancer Cell;Breast Cancer Model;Cancer Biology;Cancer Etiology;Carcinoma;cell motility;Cells;Cessation of life;chemical property;Chemicals;chemokine;Circulation;Collagen;Complex;Computer Models;Computer Simulation;Coupling;Data;Development;Disease;Environment;Event;Extracellular Matrix;Feedback;Fibroblasts;Hemidesmosomes;Heterogeneity;Human;Hypoxia;insight;Integrins;Intercellular Junctions;Invaded;Lead;live cell imaging;Lymphatic;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;mechanical properties;mechanical signal;Mechanics;mechanotransduction;Mediating;Microfluidic Microchips;Microfluidics;migration;Molecular;Motility;mouse model;Movement;Neoplasm Circulating Cells;Neoplasm Metastasis;neoplastic cell;novel;Organ;Organoids;Pathway interactions;polarized cell;preservation;Primary Neoplasm;Production;Regulation;response;Signal Transduction;single-cell RNA sequencing;Source;Stromal Cells;Stromal Neoplasm;Subgroup;Testing;transcriptome sequencing;treatment response;tumor;Tumor Cell Invasion;tumor microenvironment;tumor progression

PROJECT_TITLE: Leader cell development and function in Breast Tumor Collective Migration


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Conditions Affecting the Embryonic and Fetal Periods;Contraception/Reproduction;HIV/AIDS;Immunization;Infectious Diseases;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Vaccine Related;Vaccine Related - AIDS;Women's Health Research

PHR: Cytomegalovirus (CMV) can be transmitted from mother to fetus causing significant disabilities. It is important to find strategies that will either prevent or lessen the risk of virus acquisition for women, thus reducing the risk of damaging congenital CMV infection in their infants. The proposed project seeks to prevent maternal CMV infections by increasing CMV risk-reduction behaviors in urban pregnant women.

PI_NAMEs: FOWLER, KAREN B (contact)

PROGRAM_OFFICER_NAME: CHAKHTOURA, NAHIDA ABDO

PROJECT_TERMS: acceptability and feasibility;Adherence;Age;American;Anxiety;Attention;Avidity;Behavior;behavior change;Behavior Therapy;Behavioral;Biological Assay;Blood specimen;Child;Clinic;Cognitive Therapy;cohort;college;congenital cytomegalovirus;Control Groups;Counseling;Cytomegalovirus;Cytomegalovirus Infections;disability;Discipline of obstetrics;DNA;Dose;Education;efficacy evaluation;Electronic Mail;Enrollment;Ethnic Origin;Ethnic Population;evidence base;Exposure to;Family;Fetus;follow-up;Friends;Goals;group intervention;Gynecologist;Healthcare;high risk;High Risk Woman;Home;Hygiene;Immunoglobulin G;Immunoglobulin M;indexing;Infant;Infection;infection rate;infection risk;innovation;Intervention;Intervention Trial;Knowledge;Life;Maternal-Fetal Transmission;Measures;Medical Records;Mothers;next generation sequencing;offspring;Oral;Outcome;Outcome Study;Participant;Patient Self-Report;Population;post intervention;Pregnancy;Pregnant Women;prenatal;Prenatal care;prenatal health;prevent;Prevention;Primary Infection;primary outcome;protective behavior;psychosocial;Questionnaires;Race;racial population;Randomized;randomized, controlled study;Randomized, Controlled Trials;recruit;Reporting;Research;response;Risk;Risk Behaviors;Risk Factors;Risk Reduction;Risk Reduction Behavior;Saliva;sample collection;screening;secondary endpoint;seroconversion;Serology;Serology test;seropositive;Sex Behavior;skills;Source;Specimen;Stress;stress reduction;Text;theories;Third Pregnancy Trimester;transmission process;trial enrollment;Umbilical Cord Blood;Urine;Vaccination;vaccine development;Vagina;Variant;viral DNA;Viral Load result;Virus;Virus Shedding;Visit;Woman

PROJECT_TITLE: Prenatal behavioral intervention to prevent maternal cytomegalovirus in pregnancy

STUDY_SECTION: CMPC

STUDY_SECTION_NAME: Clinical Management of Patients in Community-based Settings Study Section[CMPC]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Chronic Pain;Neurosciences;Pain Research

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative Pain is currently the most common cause of long-term disability in the United States, affecting over 70 million Americans and 1.5 billion people worldwide. The first line of treatment for pain has been opioids, however their use is associated with addiction, dependence and overdose. The objective of this proposal is to rigorously and mechanistically explore the role of an important motivational circuit in inflammatory pain driven changes in behavior, with the long term goal of identifying a novel circuit target for treatment of inflammatory pain.

PI_NAMEs: KASH, THOMAS L. (contact)

PROGRAM_OFFICER_NAME: GREENWELL, THOMAS

PROJECT_TERMS: Acute;Acute Pain;addiction;Affect;Affective;American;antinociception;Automobile Driving;Behavior;Behavioral;Brain;Calcium;chronic pain;chronic pain management;Clinical;Corticotropin-Releasing Hormone;CRISPR/Cas technology;Data;Dependence;Development;Dopamine;Dopamine Receptor;dopaminergic neuron;emotional behavior;Exhibits;Genetic;Goals;heat stimulus;Image;in vivo;in vivo calcium imaging;inflammatory pain;insight;Link;Long term disability;Measurement;Mediating;midbrain central gray substance;Motivation;Mus;Neurons;Nociception;nociceptive response;novel;novel strategies;Opioid;Overdose;Pain;Pain management;Persons;pharmacologic;Physiological Adaptation;Physiology;Play;Population;Property;receptor;receptor function;Rewards;Role;Signal Transduction;Signaling Molecule;Site;Slice;Structure of terminal stria nuclei of preoptic region;System;Testing;United States

PROJECT_TITLE: Determining the impact of BNST CRF systems on inflammatory pain-induced disruptions of behavior

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: Los Angeles

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE The Children’s Oncology Group (COG) is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. Over 220 leading children’s hospitals, universities, and cancer centers across US, Canada and other countries participate in COG research, which is focused on developing better treatments that can improve the cure rate and outcome for all children with cancer.

PI_NAMEs: ALONZO, TODD A (contact)

PROGRAM_OFFICER_NAME: MOONEY, MARGARET M

PROJECT_TERMS: 1 year old;Acceleration;Acute;Acute Myelocytic Leukemia;Adolescent;anti-cancer research;Australia;Biology;Brain Stem Glioma;Canada;Cancer Center;Cancer Patient;cancer therapy;Caring;Cause of Death;Cell Therapy;chemotherapy;Child;Child Support;Childhood;childhood cancer survivor;Childhood Cancer Treatment;Childhood Leukemia;Clinical;Clinical Research;clinical translation;Clinical Trials;Clinical Trials Cooperative Group;Clinical Trials Design;Collaborations;Collection;Communities;Companions;Complication;Country;Data;data centers;Data Coordinating Center;data management;data sharing;density;design;Development;Diagnosis;Disease;Ensure;experience;Family;Foundations;Functional disorder;functional outcomes;Generations;Genomics;Goals;health related quality of life;high risk;Hormonal;Immunotherapy;improved;improved outcome;Industry;Infrastructure;innovation;Institution;Interdisciplinary Study;Knowledge;Laboratories;Late Effects;Malignant Childhood Neoplasm;Malignant Neoplasms;member;Methods;Mission;Molecular;Morbidity - disease rate;mortality;multidisciplinary;National Cancer Institute;National Clinical Trials Network;Neuroblastoma;New Zealand;novel;novel therapeutic intervention;Organ;organizational structure;Outcome;Patients;Pediatric Hospitals;Pediatric Oncology Group;Pharmaceutical Preparations;Population Heterogeneity;Population Research;Prognosis;programs;Quality of life;Rare Diseases;Reporting;reproductive;Research;Research Personnel;Science;Second Primary Cancers;small molecule;statistics;Survival Rate;Survivors;survivorship;Tissues;translational clinical trial;Translational Research;translational scientist;translational study;trial design;United States;Universities;Work

PROJECT_TITLE: Children's Oncology Group Statistics and Data Center


ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Project Narrative The incidence of type 1 diabetes (T1D), an autoimmune disease which affects millions of people worldwide, has been rising for the past half century. While both genetic and environmental factors contribute to the risk of developing T1D, recent studies indicate that early-life microbial interactions with the developing immune system offer a critical window of opportunity to influence the immune system’s development to prevent disease. Our study uses an innovative approach that leverages a community of early life microbes to identify microbial products and immune system pathways that may lead to therapies to prevent the development of T1D.

PI_NAMEs: SILVERMAN, MICHAEL A (contact)

PROGRAM_OFFICER_NAME: SPAIN, LISA M

PROJECT_TERMS: Adult;Affect;Alleles;Anatomy;Antigen Presentation;Antigens;Autoantigens;Autoimmune Diabetes;Autoimmune Diseases;Autoimmunity;Bacteria;Birth;CD4 Positive T Lymphocytes;Cells;Child;Childhood;Communities;Complex;Data;Development;Diabetes Mellitus;diabetes pathogenesis;Disease;early life exposure;effective therapy;Environmental Risk Factor;Exposure to;Genetic;genetic linkage;Genetic Models;Germ-Free;Gnotobiotic;Goals;Growth;gut microbes;gut microbiome;Haplotypes;Histocompatibility Antigens Class II;HLA Antigens;host microbiota;Human;Immune;Immune response;Immune system;Immunization;immunoregulation;In Vitro;in vivo;Inbred NOD Mice;Incidence;innovation;insight;Insulin-Dependent Diabetes Mellitus;intestinal homeostasis;Intestines;Investigation;islet autoimmunity;Knowledge;Life;Major Histocompatibility Complex;Maps;mass spectrometric imaging;Mediating;member;Metabolic;metabolomics;Microbe;microbial;microbial community;microbial products;microbiome;microbiota;microorganism antigen;microorganism interaction;Modeling;mouse model;Mucous Membrane;Mus;Pathway interactions;Peptides;Peripheral;Persons;Phylogenetic Analysis;Predisposition;prevent;Property;protective effect;Proteins;Publishing;rational design;Regulatory T-Lymphocyte;Research;response;restraint;Risk;Role;Shapes;Site;System;Systems Development;T cell receptor repertoire sequencing;T cell response;T-Lymphocyte;Testing;Therapeutic;Time;tool;Transgenic Mice;Transgenic Organisms;transmission process;validation studies;Weaning;Work

PROJECT_TITLE: Leveraging early-life microbes to prevent type 1 diabetes

STUDY_SECTION: HAI

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


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Eye Disease and Disorders of Vision;Liver Disease;Orphan Drug;Rare Diseases

ORG_CITY: ATLANTA

ORG_NAME: ONCOSPHERIX, INC.

ORG_STATE: GA

PHR: Project narrative  Uveal melanoma (UM) is the most common malignant eye tumor in adults. In approximately half of the patients, the cancer cells metastasize to the liver despite using either surgery or radiation to control tumors in the eye, and this tumor spread leads to patient demise. This SBIR focuses on advancing a safe and effective drug called 64B that inhibits the function of hypoxia inducible factors (HIFs) and improves tumor control in preclinical models of UM. Based on its novel mechanism of action and pre-clinical demonstrations of stand-alone therapeutic efficacy and synergy with other oncologic therapeutics, our goal is to advance 64B into clinical trials for use in humans in combination with another oncologic therapeutic drug to improve quality of life and longevity in patients with high risk and metastatic UM.

PI_NAMEs: OFFERMANN, MARGARET KENNY (contact)

PROGRAM_OFFICER_NAME: ZHAO, MING

PROJECT_TERMS: acute toxicity;Adult;Alabama;amorphous solid;Antitumor Response;BAY 54-9085;Behavioral;bHLH-PAS factor HLF;Body Weight decreased;Bolus Infusion;cancer cell;Canis familiaris;catalyst;Cell Line;Cell Survival;cell type;Cells;Chemistry;Chromatography;Clinical Research;Clinical Trials;cofactor;Combined Modality Therapy;Complement;Coupled;CRISPR/Cas technology;Development;Dose;efficacy study;EP300 gene;Excipients;Eye;Formulation;Funding;Genetic Transcription;Goals;high risk;Human;Hypoxia Inducible Factor;hypoxia inducible factor 1;Implant;improved;in vivo;inhibitor;innovation;insight;Laboratories;Liver;Longevity;malignant neoplasm of eye;Malignant Neoplasms;manufacture;manufacturing process;Maximum Tolerated Dose;Melanoma Cell;Metabolic;Metastatic Neoplasm to the Liver;Methods;Microscopic;microwave electromagnetic radiation;Modeling;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;novel;Operative Surgical Procedures;Oral;Oral Administration;Organ;Palladium;parenteral administration;Patients;Pharmaceutical Preparations;Phase;phase 2 study;Plasma;pre-clinical;Pre-Clinical Model;preclinical study;prevent;Primary Neoplasm;Process;Production;Protocols documentation;Publishing;Quality of life;Radiation;Rattus;recruit;research clinical testing;response;Role;Secure;Small Business Innovation Research Grant;small molecule therapeutics;Solubility;synergism;Testing;Therapeutic;Toxic effect;Toxicology;transcription factor;Treatment Efficacy;tumor;tumor behavior;tumor growth;Tyrosine Kinase Inhibitor;Uvea;Uveal Melanoma;Work

PROJECT_TITLE: Arylsulfonamides for the Treatment of Primary and Metastatic Uveal Melanoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CTH-T(10)B]


NIH_SPENDING_CATS: Bioengineering;Data Science;Diabetes;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: EMORY UNIVERSITY

PHR: Project Narrative Diabetes is known to be highly heterogeneous with various phenotypes, causes and outcomes. Current effective subtyp- ing of diabetes is limited due to the inability of modeling complex disease variables potentially interconnected across multiple modalities of patient data. This project develops a novel and practical analytic tool to understand the hetero- geneity of diabetes to enhance its precise detection, in-depth analysis and personalized treatment.

PI_NAMEs: YANG, JI (CARL)  (contact)

PROGRAM_OFFICER_NAME: WANG, XUJING

PROJECT_TERMS: advanced analytics;Amputation;analytical tool;Behavioral;Biological Markers;Biotechnology;Blindness;Caring;Characteristics;Chronic Disease;Clinical;Clinical Data;clinical phenotype;clinical practice;clinically actionable;cohort;combinatorial;comorbidity;Complex;complex data;computer science;computer scientist;Computer software;cost;cost effective treatment;Data;Data Science;Data Set;data structure;design;Detection;Development;diabetes management;Diabetes Mellitus;diabetic;diabetic patient;digital;Disease;Disease Progression;Early Diagnosis;Early Intervention;Economic Burden;Economics;effective therapy;Electronic Health Record;Electronics;Environmental Risk Factor;Epidemic;Genomics;Goals;Grain;Graph;graph neural network;Health;health data;Healthcare;Healthcare Systems;Heart Diseases;Heterogeneity;high risk;Human;improved;Individual;individual patient;individual variation;Information Networks;insight;Institution;Kidney Diseases;Life Experience;Machine Learning;machine learning model;Measures;Methods;Mining;Modality;Modeling;Modernization;Molecular;multimodal data;multimodality;multiple omics;National Institute of Diabetes and Digestive and Kidney Diseases;Neural Network Simulation;Non-Insulin-Dependent Diabetes Mellitus;novel;open source;Outcome;outcome prediction;Pathologic;patient response;Patients;Pattern;personalized medicine;Phenotype;Population;precision medicine;Prediabetes syndrome;Prevalence;Production;prototype;Records;Research;Research Personnel;secondary analysis;sensor;social;social factors;Social Interaction;Source;Structure;Surveys;Symptoms;System;therapy design;time interval;Training;Translating;Translational Research;treatment effect;treatment strategy;United States;United States National Institutes of Health

PROJECT_TITLE: Understanding Diabetes Heterogeneity via Mining Multimodality Interconnected Data

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]