NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Genetics;HIV/AIDS;Immunization;Infectious Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention;Vaccine Related

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: RELEVANCE (See instructions): HIV/AIDS continues to be a major health challenge worldwide. The statistical methods which will be  developed under this proposal will lead to more efficient clinical trials, better characterization of the  epidemic and more effective laboratory studies of HIV, and will be relevant to other infectious diseases as  well.

PI_NAMEs: HUGHES, JAMES P (contact)

PROGRAM_OFFICER_NAME: GEZMU, MISRAK

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;active control;Address;Adopted;Affinity;age related;AIDS prevention;Algorithm Design;Algorithms;Alleles;Antibodies;Antigens;antiretroviral therapy;Area;Attention;B-Cell Antigen Receptor;B-cell receptor repertoire sequencing;B-Lymphocytes;Base Pairing;Base Sequence;Benchmarking;Binding;Biological;Biological Assay;Biological Markers;Blood Tests;CD4 Lymphocyte Count;CD4 Positive T Lymphocytes;Chronic Disease;Clinic Visits;Clinical;Clinical Research;Clinical Trials;Clinical Trials Design;Communicable Diseases;Complex;computerized tools;Confidence Intervals;Consensus Sequence;cost;cost effective;Cox Proportional Hazards Models;Data;deep neural network;deep sequencing;design;Development;Dimensions;Disease;Drug resistance;Effectiveness of Interventions;effectiveness study;Epidemic;Ethics;Evaluation;Event;Evolution;Exhibits;Flow Cytometry;follow-up;Future;Genetic Recombination;Genotype;Geography;Germ Lines;Grant;hazard;Health;HIV;HIV Infections;HIV prevention trial;HIV vaccine;HIV Vaccine Trials Network;HIV/AIDS;Household;Immune;Immunization;Immunoglobulin Genes;Immunoglobulin Somatic Hypermutation;Immunoglobulins;Immunologics;improved;Incidence;Individual;insight;Instruction;interest;International;Intervention;intervention effect;Joints;Knowledge;Laboratory Study;latent HIV reservoir;Lemmings;Life Expectancy;Light;Linear Programming;Machine Learning;Maximum Likelihood Estimate;Measures;Methodology;Methods;Minority;Modeling;mortality;multidimensional data;neutralizing antibody;New Agents;next generation sequencing;novel;Outcome;Participant;Patients;Performance;Periodicals;Pharmaceutical Preparations;placebo controlled trial;Placebos;Population Heterogeneity;pre-exposure prophylaxis;predictive modeling;Process;Progress Reports;Property;Protocols documentation;Quality of life;Relaxation;Research;response;Risk Factors;Sample Size;screening;Screening Result;sequencing platform;Series;simulation;Software Tools;Statistical Methods;Statistical Models;Stochastic Processes;Stroke;Surveys;Testing;theories;Time;time interval;treatment choice;treatment effect;Treatment Factor;treatment strategy;treatment trial;trial design;Update;vaccine trial;Vaccines;Variant;Viral;Viral Load result;Virus;volunteer;Work

PROJECT_TITLE: Statistical Issues in AIDS Research


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Contraception/Reproduction;Estrogen;Uterine Cancer;Women's Health Research

ORG_CITY: IOWA CITY

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative/Public Health Relevance Statement While outcomes have substantially improved for many types of cancer, endometrial cancer incidence and deaths are on the rise, due in large part to inadequate sensitivity to hormonal therapy. Our study is anticipated to revitalize hormonal therapy for endometrial cancer by determining the mechanisms underlying loss of progesterone receptor, which dictates response to hormonal therapy, and successfully combining agents that overcome this hormone receptor suppression. Our research plan, which incorporates valuable clinical specimens from patients and a human-in-mouse tumor xenograft mouse model, is anticipated to have a positive impact by developing molecularly enhanced hormonal therapy to improve outcomes for patients with endometrial cancer.

PI_NAMEs: YANG, SHUJIE  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Aftercare;analog;Apoptosis;Area;Automobile Driving;Biopsy;cancer cell;cancer clinical trial;Cancer Model;Cancer Patient;cancer type;Cell Line;Cessation of life;Clinical;Clinical Research;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Data;derepression;design;differentiation in vitro;Down-Regulation;drug candidate;drug efficacy;Drug Screening;drug testing;Effectiveness;Endometrial;Endometrial Carcinoma;Endometrium;Epigenetic Process;Estrogens;evidence base;first-in-human;Future;Gene Silencing;Genes;genome-wide;Genomics;Goals;Growth;HDAC2 gene;HDAC4 gene;Histologic;Histone Deacetylase Inhibitor;Hormonal;Hormone Receptor;hormone therapy;Human;human model;human tissue;Hysterectomy;improved;improved outcome;In Vitro;in vitro Model;in vivo;Incidence;inhibitor;innovation;Intervention;Invaded;knock-down;Knock-out;Laboratories;Libraries;MAP Kinase Gene;Measures;medication safety;Medroxyprogesterone 17-Acetate;Molecular;mouse model;Mus;neoplastic cell;novel;novel strategies;novel therapeutics;Operative Surgical Procedures;Outcome;participant enrollment;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;PIK3CG gene;Pilot Projects;preclinical study;Prior Therapy;Progesterone;Progesterone Receptors;Progestin Therapy;Progestins;public health relevance;Publishing;Randomized;Receptor Down-Regulation;receptor downregulation;receptor expression;Receptor Inhibition;recruit;Recurrence;Regimen;Regulation;Reporter Genes;Research;Resistance;response;safety and feasibility;SETDB1 gene;Site;small molecule;Specimen;stem;Survival Rate;Testing;Therapeutic Intervention;Time;Topoisomerase-II Inhibitor;treatment choice;trend;tumor;Tumor Suppressor Proteins;tumor xenograft;United States National Institutes of Health;Uterus;Work;Xenograft Model

PROJECT_TITLE: Restoring Progestin Sensitivity in Endometrial Cancer


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

ORG_CITY: CHAPEL HILL

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: While recent successes of cancer immunotherapy have generated considerable excitement, this form of treatment has been largely ineffective in patients with pancreatic cancer. A major barrier for immunotherapeutic approaches is immune suppression instigated by pancreatic tumor and stromal cells. We have identified IL35- producing B cells as important regulators of anti-tumor immune responses in pancreatic cancer, and our proposed research will shed light on the mechanisms by which these cells elicit pancreatic tumor growth and will provide us with novel therapeutic targets that could be used to synergize with existing immunotherapeutic approaches.

PI_NAMEs: PYLAYEVA-GUPTA, YULIYA  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Address;Affect;anti-PD-1;anti-tumor immune response;Antibody Therapy;Antigens;Autoimmunity;Autologous;B-Cell Antigen Receptor;B-Lymphocyte Subsets;B-Lymphocytes;Biological Assay;Blood;Bone Marrow;cancer cell;Cancer Etiology;cancer immunotherapy;CD19 gene;CD8-Positive T-Lymphocytes;Cell Line;Cell Physiology;Cell Proliferation;Cells;Cessation of life;Chemosensitization;Circulation;Coculture Techniques;cytokine;cytotoxic;cytotoxic CD8 T cells;Data;design;Diagnosis;Disease;effector T cell;efficacy evaluation;Evolution;exhaustion;FOXP3 gene;Frequencies;Gene Expression Profile;Genetic;Goals;Growth;healthy volunteer;Hen Egg Lysozyme;Human;Immune;immune checkpoint blockade;Immunologic Surveillance;immunoregulation;Immunosuppression;Immunotherapeutic agent;Immunotherapy;in vivo;insight;Knock-out;lymph nodes;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;Melanoma;mouse model;Mus;new therapeutic target;novel;novel therapeutic intervention;Operative Surgical Procedures;pancreas development;pancreatic cancer cells;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;pancreatic neoplasm;Pathogenicity;Pathway Analysis;Pathway interactions;Patients;peripheral blood;pharmacologic;Production;Publishing;Receptor Signaling;reconstitution;Regulatory T-Lymphocyte;Research;Resected;Resistance;response;Role;Shapes;Signal Pathway;Signal Transduction;Solid;Spleen;Stromal Cells;success;Surveillance Program;Survival Rate;synergism;T cell infiltration;T-Lymphocyte;Testing;Therapeutic;therapy resistant;Time;Tissues;TNFRSF5 gene;translational potential;Translations;tumor;tumor growth;Tumor Immunity;tumor microenvironment;Tumor Promotion;tumor-immune system interactions;Up-Regulation

PROJECT_TITLE: Function of IL35+ B cells in pancreatic cancer


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cancer;Chronic Pain;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Ovarian Cancer;Pain Research;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Rural Health;Social Determinants of Health;Women's Health Research

ORG_CITY: DURHAM

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: DUKE UNIVERSITY

PHR: Narrative Ovarian cancer (OC) survival has improved over the past several decades as new, frontline treatment strategies have been developed; however, the benefits of improved treatment have not been shared equitably. Given the immense complexity of cancer treatment and the importance of access to quality care, an improved understanding of factors underlying access to care – and an understanding of how those factors differ across population sub-groups – is urgently needed. Our proposed extension will comprehensively evaluate the impact of structural racism on healthcare access, quality treatment and survival among diverse OC patients.

PI_NAMEs: AKINYEMIJU, TOMI F (contact)

PROGRAM_OFFICER_NAME: CRONIN, KATHLEEN A

PROJECT_TERMS: Address;Adjuvant;Aftercare;Area;Attitude;barrier to care;black patient;Black race;black women;cancer care;cancer epidemiology;cancer health disparity;Cancer Patient;cancer survival;Cancer Survivor;cancer therapy;Caring;Cessation of life;chemotherapy;Chronic stress;cohort;Complex;Cost Sharing;Data;Data Set;Databases;Development;differences in access;Dimensions;Discrimination;Disparity;disparity reduction;Equation;Equity;Fatigue;female reproductive system;Financial Hardship;Guidelines;Health;health care availability;health care service organization;health difference;health literacy;Health Personnel;Health Services Accessibility;Healthcare;Hospitals;improved;Individual;insight;Joints;Knowledge;Link;Literature;Location;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Medicare;Mental Depression;Modeling;mortality;National Cancer Institute;Neighborhoods;neoplasm registry;Not Hispanic or Latino;Operative Surgical Procedures;Outcome;Pain;Parents;Pathway interactions;Patient Outcomes Assessments;patient-clinician communication;Patients;Patterns of Care;perceived discrimination;Perception;Pharmaceutical Preparations;Platinum;Population;population based;Poverty;preference;Provider;Quality of Care;Quality of life;Race;racial difference;racial disparity;racial population;racism;Recommendation;recruit;Reporting;Research Infrastructure;Research Personnel;residential segregation;Resources;Role;Rural;SEER Program;Social support;socioeconomics;Source;Specialist;Structural Racism;Subgroup;Supportive care;surveillance data;Surveys;survival disparity;survival outcome;Survival Rate;Survivors;Symptom Burden;Symptoms;theories;Therapeutic;Time;translational impact;Travel;Treatment outcome;treatment strategy;trend;Trust;Tumor Debulking;White Women;Woman

PROJECT_TITLE: A Role of Multilevel Healthcare Access Dimensions in Ovarian Cancer Disparities


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: LA JOLLA

ORG_NAME: J. CRAIG VENTER INSTITUTE, INC.

ORG_STATE: CA

PHR: PROJECT NARRATIVE Acute myeloid leukemia (AML) treatment is insufficient even with the latest novel therapeutics, and the overall prognosis is still poor. The JMJD1C protein has been shown to be a potential therapeutic target in AML. The proposed work aims to study the effectiveness of combining JMJD1C modulation and inhibitors against RAS protein pathway, which are commonly mutated in AML, in eliminating leukemia cells in AML with RAS activating mutation.

PI_NAMEs: ZHU, NAN  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute Myelocytic Leukemia;Alleles;Apical;Applications Grants;Binding;Biochemical;Biological;Biological Assay;biomarker identification;Cells;chemotherapy;ChIP-seq;Combined Modality Therapy;Complex;conditional knockout;CRISPR/Cas technology;Data;Deacetylase;Deacetylation;demethylation;design;Disease;Disease remission;effectiveness study;Epigenetic Process;Family;Gene Expression;gene repression;genetic corepressor;Genetic Transcription;Hematopoiesis;histone demethylase;Histone H3;Histones;Human;In Vitro;in vitro activity;in vivo;inhibitor;Knockout Mice;Knowledge;leukemia;leukemia treatment;Leukemic Cell;leukemic stem cell;leukemogenesis;Lysine;Mediating;member;Methylation;MLL-AF9;MLL-rearranged leukemia;Molecular;mouse model;Mus;Mutate;Mutation;novel;novel therapeutics;overexpression;parent grant;Pathway interactions;Patients;Physical condensation;Pre-Clinical Model;Prognosis;Proteins;ras Proteins;Ras Signaling Pathway;rational design;Recurrent disease;Relapse;Resistance;resistance mechanism;Role;Sampling;self-renewal;small molecule inhibitor;stem cell biology;stem cell function;stem cell model;stem cell self renewal;Survival Rate;targeted treatment;Testing;Therapeutic Agents;Therapeutic Effect;therapeutic target;therapy outcome;Treatment Efficacy;Work;Xenograft Model;Zinc Fingers

PROJECT_TITLE: The histone demethylase JMJD1C in human Acute Myeloid Leukemia


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: ROCHESTER

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: PROJECT NARRATIVE Humans critically rely on a tiny region of the retina, the foveola, to inspect objects of interest. By examining how foveal processing is jointly shaped by anatomy, eye movements and fine control of attention, this research will advance understanding of the mechanisms responsible for visual acuity in humans and it may lay the basis for new treatment approaches for impairments in foveal functions.

PI_NAMEs: POLETTI, MARTINA  (contact)

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TITLE: Vision, Attention and Eye Movements at the Scale of the Foveola

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: RALEIGH

ORG_DEPT: MISCELLANEOUS

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: PROJECT NARRATIVE – OVERALL The mission of North Carolina Center for Coastal Algae, People, and Environment (NC C-CAPE) is to deliver novel insight and understanding of emergent and future, climate-driven human health risks related to cyanobacterial algal blooms and microcystins in shallow, estuarine environments. The integration of three research projects and a community engagement core will facilitate 1) the characterization of algal composition, microcystin concentrations, and microcystin congener mixtures in water and seafood (oysters and blue crabs) in relation to environmental conditions including toxin transport across the freshwater-to-marine continuum, 2) the examination of the effects of cyanotoxin mixtures on hepatic toxicity, fatty liver diseases, and liver cancers using a combination of a rodent model and a nested case-control study on human populations, 3) the development of predictive models for cyanotoxin risk assessment in the context of climate change, based on diverse algal bloom metrics and environmental covariates, and 4) effective data sharing to prevent bloom exposure of NC coastal communities, activate community science projects that fill data gaps, and improve translation of research findings on oceans and human health to community stakeholders. NC C-CAPE will be a nexus of climate and ocean science, human health, and stakeholder engagement to advance our understanding of harmful algal blooms, and to develop innovative approaches to assess, mitigate and predict their impacts on human health.

PI_NAMEs: BELCHER, SCOTT M;SCHNETZER, ASTRID  (contact)

PROGRAM_OFFICER_NAME: DZIERLENGA, ANIKA LIN

PROJECT_TERMS: Address;Algae;Algal Blooms;Animals;Biological Models;Blue Crab;Chronic;Circulation;Climate;climate change;climate forcing;climate science;coastal water;Collaborations;Communication;Communities;community center;community engagement;community science;Core Facility;County;cyanobacterial toxin;cyanoginosin LR;Cyanotoxin;Data;Data Set;data sharing;design;Detection;Development;Disease Progression;diverse data;Droughts;Ecosystem;Ensure;Environment;Environmental Monitoring;Epidemiology;epidemiology study;Eutrophication;Event;experimental study;fatty liver disease;field survey;Fishes;Frequencies;Fresh Water;Funding;Future;Goals;Guidelines;harmful algal blooms;Health;Hepatocyte;Hepatotoxicity;High Performance Computing;Human;improved;In Situ;Infrastructure;innovation;insight;Justice;Knowledge;land use;Leadership;Link;Lived experience;Liver;Liver diseases;Malignant neoplasm of liver;marine;Measures;member;microcystin;Mission;Modeling;Monitor;mouse model;multidisciplinary;Nested Case-Control Study;non-alcoholic fatty liver disease;North Carolina;novel;Oceanography;Oceans;Outcome;Oysters;Persons;Population;Positioning Attribute;predictive modeling;predictive tools;prevent;Prevention;Primary carcinoma of the liver cells;Procedures;Process;Reporting;Research;Research Project Grants;Research Support;Risk;Risk Assessment;risk prediction;Risk Reduction;Rodent;Rodent Model;Sampling;Science;Seafood;Shellfish;Site;sound;spheroids;Statistical Models;System;Technology;toxic algae;Toxic effect;Toxicology;Toxin;Translational Research;trend;United States National Institutes of Health;Water;Water consumption;Work

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 LKB-K (P)]


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Social Determinants of Health

PI_NAMEs: SCHNETZER, ASTRID  (contact)

PROJECT_TERMS: Achievement;Administrative Efficiency;Adopted;Advisory Committees;Algae;Algal Blooms;Animals;Area;Bayesian Network;Biological;Blue Crab;Businesses;Circulation;Climate;Collaborations;Communication;Communities;community advisory board;community engagement;community science;connected health;Cyanotoxin;Data;Data Collection;Data Set;data sharing;Decision Making;Discipline;diverse data;Ecology;Ecosystem;Ensure;Environment;Environmental Health;Equilibrium;Event;Feedback;Fostering;Fresh Water;Future;Goals;harmful algal blooms;Health;Hepatotoxicity;Human;improved;Individual;Infrastructure;interdisciplinary approach;interest;Justice;Knowledge;Leadership;Logistics;Malignant neoplasm of liver;marine;meetings;member;Mentors;Modeling;National Institute of Environmental Health Sciences;non-alcoholic fatty liver disease;North Carolina;Oceanography;Oceans;Organizational Culture;Output;Oysters;Performance;Personnel Management;Persons;Plankton;Population;predictive modeling;Process;Program Evaluation;Recommendation;Recreation;remote sensing;Reporting;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;Risk;Role;Science;Scientist;Series;Shapes;Shellfish;Structure;Students;success;symposium;synergism;System;Toxic effect;Toxicology;Training and Education;Translations;Water

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Social Determinants of Health

PROJECT_TERMS: Accountability;Address;Advocacy;Advocate;Algae;archive data;Black, Indigenous, People of Color;Businesses;citizen science;Code;Collaborations;Communities;community advisory board;community engagement;community science;Cyanotoxin;Data;Data Collection;data hub;data management;Data Set;data sharing;Data Sources;design;Disease;Disparity;Ecosystem;Educational Curriculum;Educational workshop;Ensure;Environment;Environmental Health;environmental health disparity;environmental justice;Event;expectation;experience;Future;Geography;Goals;Guidelines;harmful algal blooms;hazard;Health;Health Priorities;Hour;Human;human subject protection;improved;informal learning;Infrastructure;innovation;insight;Institutional Review Boards;Intention;Investments;Justice;Knowledge;Leadership;Lived experience;Logistics;marginalized community;marginalized population;member;Metadata;Methods;Monitor;Newsletter;North Carolina;Oceanography;Oceans;open data;Outcome;Persons;Phytoplankton;predictive tools;Procedures;Program Evaluation;Publishing;recruit;Research;Research Personnel;Risk;Scientist;Seafood;Spanish/English;Specialist;success;Techniques;Toxin;Training;volunteer;Water;Water consumption;Work

PROJECT_TITLE: Community Engagement Core


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Digestive Diseases;Foodborne Illness;Liver Disease

PROJECT_TERMS: Acute;Address;Affect;Algae;Algal Blooms;Animals;bioaccumulation;Biological;Blue Crab;Body Burden;Cells;Chronic;Climate;climate change;coastal water;cohort;Communities;community center;community engagement;community science;Complement component C1;Consumption;contaminated seafood;cyanobacterial toxin;Cyanotoxin;Data;data sharing;Detection;Documentation;Drug Metabolic Detoxication;Ecosystem;Environment;Epidemiology;Equilibrium;Eutrophication;Event;Exposure to;field survey;Fisheries;Future;future climate scenario;Goals;Habitats;harmful algal blooms;Health;Hepatotoxicity;High temperature of physical object;Human;In Situ;insight;Kinetics;Link;Malignant neoplasm of liver;marine;Methodology;microcystin;Modeling;Monitor;mouse model;Muscle;North Carolina;Oysters;Pattern;Persons;Poisoning;predictive modeling;Proliferating;Public Health;Recreation;Research Personnel;Research Project Grants;Resources;response;Risk;Risk Assessment;risk prediction;Sampling;Seafood;Seasons;Seawater;sensor;severe weather;Shellfish;shellfish contamination;Site;sound;Source;spatiotemporal;Statistical Models;System;Temperature;Testing;Time;Tissues;Toxic effect;Toxin;Translating;uptake;vector;Viscera

PROJECT_TITLE: Examining Linkages among Microcystins, Shellfish Contamination, and Toxin Transfer in Oysters and Blue Crabs across a Coastal North Carolina Sound


NIH_SPENDING_CATS: Cancer;Chronic Liver Disease and Cirrhosis;Climate-Related Exposures and Conditions;Clinical Research;Digestive Diseases;Foodborne Illness;Liver Cancer;Liver Disease;Rare Diseases

PROJECT_TERMS: Acute;Algae;Animals;Arsenic;Biological Markers;Biological Models;Biological Monitoring;Biomedical Research;Cadmium;carcinogenicity;case control;Chemicals;Chronic;Clinical;cohort;Cohort Studies;Communities;cyanoginosin LR;Data;data modeling;data repository;Derivation procedure;Dose;drinking water;Environment;Environmental Pollution;Epidemiology;epidemiology study;experience;experimental study;Exposure to;Fatty Liver;Female;Future;Geography;Goals;harmful algal blooms;hazard;Health;Hepatotoxicity;HepG2;Human;human data;In Vitro;in vivo;Individual;Intervention;Laboratories;Liver;Liver diseases;Liver Fibrosis;male;Malignant neoplasm of liver;Measures;Mediating;Metabolic;microcystin;Monitor;mouse model;Mus;National Institute of Environmental Health Sciences;Nested Case-Control Study;non-alcoholic fatty liver disease;North Carolina;novel;Oceans;Organ;Outcome;Participant;perfluorooctane sulfonate;Persons;Phenotype;Policies;pollutant;Poly-fluoroalkyl substances;Population;predictive modeling;Primary carcinoma of the liver cells;Public Health;Questionnaires;Reference Values;Reporting;Research;Research Project Grants;Risk;Risk Assessment;Seafood;secondary analysis;sound;Specimen;spheroids;Sulfonic Acids;System;Testing;therapeutic target;three-dimensional modeling;Toxic effect;toxic metal;Toxicity Tests;Toxin;uptake;Water Supply;water treatment

PROJECT_TITLE: Human Epidemiologic and Toxicity Assessment of Microcystin Mixture Effects on Hepatic Disease and Cancer


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Foodborne Illness;Social Determinants of Health

PROJECT_TERMS: Affect;Algae;Algal Blooms;Area;Bayesian Modeling;Bayesian Network;Body Burden;Circulation;Climate;climate change;coastal water;community engagement;Complex;contaminated seafood;contaminated water;Coupled;Cyanobacterium;Cyanotoxin;Data;Data Analyses;data integration;Data Set;Development;Dimensions;diverse data;Environment;Environmental Risk Factor;Event;Experimental Designs;Exposure to;Fresh Water;Future;Goals;Habitats;harmful algal blooms;Health;high risk;Human;hydrodynamic model;Knowledge;land use;Lead;Literature;Location;Machine Learning;Maps;marine;Measurement;Measures;microcystin;Mission;Modeling;Monitor;North Carolina;novel strategies;Nutrient;Outcome;Output;Oysters;Persons;Population;predictive tools;Production;programs;Public Health;remote sensing;Research;Research Project Grants;Resolution;Risk;Risk Assessment;risk prediction;sea level rise;Severities;solar radiation;sound;Source;Spatial Distribution;spatiotemporal;Study models;System;Temperature;Time;Tissues;tool;Toxin;Update;user-friendly;Water;water quality

PROJECT_TITLE: Predicting Cyanotoxin Risks under Current and Future Climate along the Freshwater-to-Marine Continuum


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_DEPT: ZOOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: The goal of the Scripps Center for Oceans and Human Health (SCOHH) is to advance the science of marine contaminants and seafood security. This multidisciplinary project involving ocean and human health scientists will examine the sources, fates, and toxicology of anthropogenic and natural chemicals in the ocean, and to probe their environmental distribution and movement through the seafood chain in a changing climate. Importantly, SCOHH will bridge science discovery, environmental health literacy, and community engagement to build capacity for public health risk prevention while highlighting the health benefits of consuming fish.

PI_NAMEs: HAMDOUN, AMRO M;MOORE, BRADLEY S (contact)

PROJECT_TERMS: Address;anthropogenesis;Area;Attention;Benefits and Risks;bioaccumulation;Bioenergetics;Biophysics;Biota;Cardiovascular system;Cell Line;Chemicals;Chemistry;Climate;climate change;Communication;Communities;community engagement;Consumption;data modeling;Dedications;developmental toxicity;Ecology;embryo cell;Environmental Health;experience;exposed human population;Exposure to;Fishes;Food Webs;Genomics;global health;Goals;Guidelines;Health;Health Benefit;health literacy;Heavy Metals;Human;Immune;Individual;Indoles;Intake;Learning;literacy;marine;Metals;Methylmercury Compounds;microbial;Microbiology;microbiome;Micronutrients;Minerals;Modeling;Movement;multidisciplinary;National Institute of Environmental Health Sciences;Neurologic;Oceanography;Oceans;Outcome;Persons;Pharmaceutical Preparations;Planets;Play;Policies;pollutant;polybrominated diphenyl ether;Polychlorinated Biphenyls;Polyunsaturated Fatty Acids;Prevention;Privatization;Process;Production;programs;Proteins;Public Health;reproductive;Research;Research Personnel;Research Project Grants;Risk;Role;Safety;Science;Scientist;Sea Urchins;Seafood;Security;Selenium;Social Perception;Societies;Source;technology development;Teratogens;toxicant;Toxicology;Transgenic Organisms;Xenobiotics

PROJECT_TITLE: Scripps Center for Oceans and Human Health: advancing the science of marine contaminants and seafood security


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Stem Cell Research;Stem Cell Research - Embryonic - Human

PI_NAMEs: MOORE, BRADLEY S (contact)

PROJECT_TERMS: Advisory Committees;Area;Award;Biochemistry;Biology;Budgets;Businesses;career;Collaborations;commercialization;Communication;Communities;community engagement;Dedications;Developmental Biology;distinguished professor;Educational workshop;Ensure;experience;Foundations;Funding;Funding Agency;Government;Health;Human;Human Resources;Infrastructure;innovation;Institution;Internships;Lead;Leadership;marine;meetings;member;microbial;Monitor;National Institute of Environmental Health Sciences;National Oceanic and Atmospheric Administration;Oceanography;Oceans;outreach;Persons;Pharmacologic Substance;Pharmacology;Pharmacy Schools;professor;programs;Recommendation;Reporting;Research;Research Personnel;Research Project Grants;Savings;Schedule;Science;Seafood;Security;symposium;synergism;Time;undergraduate research;undergraduate student;underrepresented minority student;United States National Institutes of Health;virtual;web site;Work

PROJECT_TITLE: Scripps Center for Oceans and Human HealthAdministrative Core


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Foodborne Illness;Patient Safety

PI_NAMEs: TALLEY, THERESA SINICROPE (contact)

PROJECT_TERMS: Advisory Committees;aquarium;Benefits and Risks;Betula Genus;Biology;California;climate change;Communication;Communication Tools;Communities;community engagement;Consumption;cooking;Development;Eating;Education;Educational workshop;Environmental Health;Event;Exhibits;Exposure to;Faculty;Festival;Fishes;Food;Fostering;Future;Goals;Group Meetings;Guidelines;Health;Health Benefit;health literacy;Health Professional;Health Sciences;Human;improved;Individual;Industry;innovation;interest;Joints;Knowledge;Link;literacy;marine;Marketing;member;Methylmercury Compounds;Motivation;National Oceanic and Atmospheric Administration;news;nutrition;Oceans;Outcome;outreach;Persons;Policies;Policy Maker;pollutant;Polychlorinated Biphenyls;Production;programs;Public Health;Reaction;Recommendation;Research;Research Project Grants;Resources;Risk;Safety;sample collection;Schools;Science;Scientist;Sea;Seafood;Security;Series;social media;Students;System;Techniques;Toxic effect;Training Programs;Translating;Translational Research;Work

PROJECT_TITLE: Community Engagement Core: Seafood risks and benefits - Science, literacy and engagement


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Dietary Supplements;Foodborne Illness;Nutrition;Prevention

PI_NAMEs: SCHARTUP, AMINA BOCARY (contact)

PROJECT_TERMS: Air;Area;Benefits and Risks;bioaccumulation;Biochemical;Bioenergetics;Biological Models;Biota;burden of illness;Chemicals;Chemistry;Circulation;Climate;climate change;Collaborations;Communities;community engagement;Complex;Consumption;Coupled;Data;data modeling;Diet;dietary;disability-adjusted life years;Ecology;Ecosystem;Energy Transfer;environmental change;Equilibrium;experience;exposed human population;Exposure to;Fatty acid glycerol esters;Fisheries;Fishes;Food Webs;Future;geochemistry;Geographic Locations;Government;Habitats;Health;Health Benefit;Human;Hypoxia;improved;innovation;Intake;Link;lipophilicity;Literature;marine;Measurement;Metabolic;Metals;Methylmercury Compounds;microbial;micronutrient deficiency;Micronutrients;Modeling;National Oceanic and Atmospheric Administration;Nature;Nutrient;Nutritional;ocean ecosystems;Oceans;Omega-3 Fatty Acids;Output;Oxidation-Reduction;particle;Persons;Phytoplankton;Plankton;Plastics;pollutant;Polychlorinated Biphenyls;Population;Process;Proteins;Public Health;Reaction;Records;Relationship-Building;Research Personnel;response;Risk;Role;Safety;Sampling;Science;Sea;Seafood;Seawater;Security;Selenium;Services;Shapes;Social Perception;Source;Specimen;Stomach;stressor;Structure;Temperature;Time;Tissues;Tracer;Work;Zooplankton

PROJECT_TITLE: Project 1 - Climate change impacts on the human intake of seafood micronutrients and contaminants


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Endocrine Disruptors;Foodborne Illness;Microbiome

PI_NAMEs: ALLEN, ERIC ELLSWORTH (contact)

PROJECT_TERMS: Algae;Anabolism;anthropogenesis;Bacteria;Basic Science;bioaccumulation;Biochemical;Biodegradation;Bioreactors;Biota;Cardiovascular Diseases;chemical standard;Chemicals;Climate;climate change;climate impact;Collaborations;Complex;Cyanobacterium;Development;dietary;Dioxins;Dioxygenases;Disease Outcome;DNA;Drug Metabolic Detoxication;Ecosystem;Environment;Enzymes;Fishes;Flame Retardants;Food Webs;Genes;Genetic;halogenation;Health;Health protection;Heavy Metals;Human;Hydroxylation;Immune System Diseases;improved;Indoles;Industrialization;Insecticides;Institution;Laboratories;Life;Light;Los Angeles;Lubricants;marine;Mercury;Metabolic Biotransformation;metabolomics;Metagenomics;metatranscriptomics;Microbe;microbial;microbial community;microbiome;microbiota;Monitor;natural product inspired;Natural Source;Nervous System Disorder;neurotoxic;Nitriles;ocean ecosystems;Oceanography;Oceans;Oxygenases;Pathway interactions;Pentas;pharmacologic;Pharmacology;Planets;pollutant;polybrominated diphenyl ether;Polychlorinated Biphenyls;Population;Process;Production;Productivity;Property;Proteins;Proteobacteria;Pyrroles;Recording of previous events;reproductive;Research;Research Personnel;Resolution;Risk;Route;Ryanodine Receptor Calcium Release Channel;Safety;Sampling;Science;Seafood;Security;Site;Source;System;Teratogens;Testing;Thyroid Hormone Receptor;Toxic effect;toxicant;Toxicology;Toxin;Translations

PROJECT_TITLE: Project 2 - The marine microbiome as a source for the synthesis, transformation, and distribution of seafood contaminants


NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Endocrine Disruptors;Foodborne Illness;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Stem Cell Research;Stem Cell Research - Embryonic - Human

PI_NAMEs: HAMDOUN, AMRO M (contact)

PROJECT_TERMS: ABCB1 gene;absorption;Address;anthropogenesis;ATP phosphohydrolase;ATP-Binding Cassette Transporters;Binding;bioaccumulation;Biological Assay;biophysical techniques;Biophysics;Cardiovascular system;Cell Line;Cell model;cell type;Cells;cellular targeting;Chemicals;Complex;Consumption;contaminated seafood;Cryoelectron Microscopy;Data;Development;Developmental Biology;developmental toxicity;developmental toxicology;early life exposure;Embryo;embryo cell;embryonic stem cell;Environment;Excretory function;exposed human population;Exposure to;Fishes;Food Chain;Foundations;Generations;Genes;Germ Lines;Goals;Health;Homologous Gene;Human;human model;Image;Immobilization;Immune;Infrastructure;innovation;knock-down;Knock-out;Knowledge;Life;Ligands;Lytechnius;marine;marine organism;Measures;Metabolism;microbial;miniaturize;model organism;Modeling;Molecular Structure;Movement;Mus;nanobodies;nanodisk;Neurologic;novel;Oceans;Outcome;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Pharmacologic Substance;Pharmacology and Toxicology;Phase;Poison;pollutant;pollutant interaction;predictive modeling;Predisposition;Proteins;Reaction;Reagent;Regulator Genes;Reporter;reproductive;reproductive fitness;Research;Resolution;Resources;Risk;Role;Route;Science;Sea Urchins;Seafood;Security;small molecule;Structure;Structure of primordial sex cell;Surface Plasmon Resonance;Teratogens;tool;Toxic effect;toxicant;Toxicology;Toxin;Transgenic Organisms;Translating;Tuna;uptake;Work;X-Ray Crystallography;Xenobiotics

PROJECT_TITLE: Bioaccumulation and developmental toxicity of seafood pollutants


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative – No change from original submission Many oral anti-cancer medications have proven effective in preventing cancer recurrence and mortality, however, treatment adherence to these oral medications, some of which are taken for years, can be challenging for cancer patients due to a variety of factors, including side effects and high costs. Since medication discontinuation can lead to lower survival rates, increased risk of recurrence, and higher healthcare costs, society will benefit from gaining a deeper understanding of the causes of medication discontinuation and knowing who are at a high risk of medication discontinuation. In this project, we will analyze the online communications between patients and healthcare providers in a patient portal and apply them as well as structured electronic medical records to predict medication discontinuation.

PI_NAMEs: YIN, ZHIJUN  (contact)

PROGRAM_OFFICER_NAME: CHOU, WEN-YING

PROJECT_TERMS: Academic Medical Centers;Adjuvant;anti-cancer;Area;Attention;Back;Biometry;Cancer Patient;cancer recurrence;cancer therapy;Cessation of life;Clinical;Code;Communication;Computer software;Computerized Medical Record;Consumption;cost;Data;Death Rate;design;Diagnosis;electronic structure;expectation;experience;Future;Health;Health Care Costs;health care delivery;Health Care Research;health care service utilization;Health Personnel;Healthcare;high risk;hormone receptor-positive;hormone therapy;Human Characteristics;human subject;improved;Intervention;Interview;Investigation;Knowledge;Knowledge Discovery;Label;language processing;Learning;Machine Learning;machine learning model;Malignant Breast Neoplasm;Malignant Neoplasms;Manuals;Medical;Methods;mobile computing;Modeling;Morbidity - disease rate;mortality;Oncology;Oral;Patient Compliance;patient engagement;patient portal;patient-clinician communication;Patients;Pharmaceutical Preparations;prevent;Probability;Process;recruit;Recurrence;Regimen;Research;Research Personnel;Resources;Risk;risk prediction;Sampling Biases;Self Administration;Semantics;Services;side effect;social cognitive theory;Societies;Sociology;Statistical Models;Surveys;Survival Rate;Technology;Test Result;Testing;Text Messaging;text searching;Time;treatment adherence;Treatment Protocols;United States;unsupervised learning;Work

PROJECT_TITLE: Prediction of Anti-Cancer Medication Discontinuation via Patient Portal Messages and Structured Electronic Medical Records


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Digestive Diseases;Genetics;Nanotechnology;Pancreatic Cancer;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative Pancreatic cancer is characterized by KRAS mutation and extreme compression of cells in the highly mechanically perturbed tumor microenvironment. We have developed devices to apply precise compressive stresses and probes that enable the rapid determination of the physical properties of cells, and discovered that KRAS and compression lead to extremely high rates of mitotic error, thereby accelerating cancer genome evolution. We will now determine how evolved cancer cells survive and proliferate far more effectively in compressive environments.

PI_NAMEs: HOLT, LIAM J (contact)

PROGRAM_OFFICER_NAME: JOHNSON, ERIC MICHAEL

PROJECT_TERMS: Acceleration;Address;Affect;Aneuploidy;Automobile Driving;barrier to care;Biological Process;Biophysics;Biopsy Specimen;Blood Vessels;cancer cell;cancer genome;CDKN2A gene;Cell Physiology;Cell Proliferation;Cell Survival;Cell Volumes;Cells;Cellular biology;centromere protein A;Chromosome 8;Chromosomes;Crowding;Data;Devices;DNA biosynthesis;DNA Sequence Alteration;Drug resistance;Drug Targeting;Environment;Evaluation;Evolution;experimental study;follow-up;Gel;gene discovery;Genes;Genetic;Growth;high throughput analysis;Homeostasis;Hypoxia;Immunosuppression;In Vitro;Individual;Inflammation;innovation;KRAS2 gene;KRASG12D;Lead;Liquid substance;MADH4 gene;Malignant neoplasm of pancreas;Malignant Neoplasms;mechanical pressure;mechanical properties;Mechanics;Microfluidics;Mitotic;Mitotic spindle;Molecular;molecular assembly/self assembly;monomer;Motion;mutant;Mutation;nanoparticle;new technology;new therapeutic target;novel strategies;Nuclear;Oncogene Activation;Oncogenes;Oncogenic;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic tumorigenesis;Parents;Patients;Phase;Phenotype;Physical environment;physical property;physical state;Physiology;PIK3CG gene;Play;Polyploidy;Positioning Attribute;Predisposition;preference;pressure;prevent;Process;Proliferating;Property;Regulation;Reproducibility;Research;resilience;Resistance;response;Ribosomes;RNA;Rupture;Signal Pathway;Signal Transduction;Solid Neoplasm;Stereotyping;Stress;stress granule;Survival Rate;Technology;Tissues;tool;TP53 gene;Translations;tumor;tumor microenvironment;Viscosity;whole genome

PROJECT_TITLE: Cancer under pressure: Mechanisms of adaptation to compressive stress


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Cancer;Dietary Supplements;Natural Products;Nutrition;Prevention;Prostate Cancer;Urologic Diseases

ORG_CITY: Chicago

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because the characterization of diterpenes that can promote degradation of the androgen receptor for a new treatment approach for prostate cancer. Therefore, the proposed research is relevant to a part of NIH’s mission which is to foster fundamental creative discoveries, innovative research strategies, and their applications as a basis for ultimately protecting and improving health.

PI_NAMEs: JOHNSON, JEREMY JAMES (contact)

PROGRAM_OFFICER_NAME: KUMAR, AMIT

PROJECT_TERMS: abiraterone;Androgen Antagonists;androgen independent prostate cancer;Androgen Receptor;androgenic;Animal Model;Apoptosis;Apoptotic;Applications Grants;Automobile Driving;Award;Benign;Binding;Binding Proteins;Biological;cancer chemoprevention;Castration;Cell Nucleus;Cell surface;Cells;Chemicals;Chemoprevention;Clinical;Clinical Trials;Creativeness;Data;Development;dietary;Dimerization;disorder risk;Diterpenes;Dose;Drug Kinetics;Drug Targeting;Dutasteride;Early Diagnosis;efficacy evaluation;endoplasmic reticulum stress;enzalutamide;Enzymes;Epithelial Cells;Estrogen Antagonists;Evaluation;FDA approved;Finasteride;Fostering;Fruit;Future;Garcinia mangostana;Genetic Polymorphism;Goals;GRP78 gene;Health;Heat-Shock Proteins 70;Immunoglobulin binding proteins;improved;In Vitro;in vivo;Individual;innovation;isoprenylation;Length;Ligands;Malignant Breast Neoplasm;Malignant neoplasm of prostate;men;Microsomes;Mission;Molecular;Molecular Chaperones;mouse model;Mus;Natural Products Chemistry;novel strategies;novel therapeutic intervention;Nuclear Translocation;Oral Administration;parent grant;Pathway interactions;Patients;PC3 cell line;Pharmaceutical Preparations;Phenotype;Phosphotransferases;prevent;Prevention;Proliferating;Property;Prostate;prostate cancer cell;prostate cancer risk;Prostate Cancer therapy;prostate carcinogenesis;Proteins;Public Health;receptor;Recombinants;Research;Resistance;Resistance development;Risk Reduction;RNA Splicing;Role;side effect;small molecule;Source;Stanolone;Structure-Activity Relationship;Testing;Therapeutic;Transfection;transgenic adenocarcinoma of mouse prostate;Transgenic Animals;treatment strategy;United States National Institutes of Health;Variant;Xanthones;Xenograft procedure

PROJECT_TITLE: Defining the role of isoprenylated xanthones from the mangosteen for enhancing degradation of full length and variant forms of androgen receptor in prostate cancer


NIH_SPENDING_CATS: Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: Narrative There is no change from the current project period. Project Narrative

PI_NAMEs: NAM, KIBO  (contact)

PROGRAM_OFFICER_NAME: AVULA, LEELA RANI

PROJECT_TERMS: 3-Dimensional;Academia;Acceleration;Accounting;Acoustics;Adjuvant Chemotherapy;advanced breast cancer;Affect;Biological Markers;Breast Cancer Patient;Breast Cancer therapy;breast imaging;Breast-Conserving Surgery;cancer subtypes;cancer therapy;chemotherapy;Clinical;Clinical Research;Computer software;contrast enhanced;cost;Diagnosis;Diameter;Early treatment;Environment;Evaluation;Frequencies;high risk;improved;improved outcome;Industry;ineffective therapies;innovation;Institution;Intercellular Fluid;Local Therapy;Malignant Breast Neoplasm;Mammary Neoplasms;Measurement;Measures;Methods;Microbubbles;Modification;Monitor;Morphology;Needles;Needs Assessment;Neoadjuvant Therapy;Normal tissue morphology;novel;novel marker;Operative Surgical Procedures;Outcome;Pathologic;Patients;Physiological;Pilot Projects;Prediction of Response to Therapy;pressure;pressure sensor;prevent;Regimen;Reporting;research clinical testing;Research Personnel;response;screening;side effect;Signal Transduction;standard of care;Subgroup;System;Techniques;Technology;Testing;Therapeutic Agents;Time;timeline;treatment response;tumor;Tumor Volume;ultrasound;uptake;Woman;women's diagnosis

PROJECT_TITLE: Monitoring neoadjuvant chemotherapy of breast cancer using 3D subharmonic aided pressure estimation


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: Decatur

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: GA

PHR: Alzheimer’s disease (AD) and stroke are two common neurological diseases that often occur in the same aging individuals including veterans, but little research has been focused on the comorbidity of these diseases. Memantine (MEM) is a NMDA receptor antagonist used for moderate to severe AD patients. The investigation will test the hypothesis that chronic MEM treatment in AD mice of mild and moderate stages can ameliorate AD progression as well as precondition the AD brain for neuroprotection against ischemic stroke that attacks <50% of AD patients.

PI_NAMEs: YU, SHAN P. (contact)

PROJECT_TERMS: abeta deposition;Acceleration;Accounting;Acute;Affinity;Aging;aging population;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease therapy;Amyloid beta-Protein;Animal Model;Animals;antagonist;Apoptotic;APP-PS1;Area;Attention;Basic Science;Behavioral;Blood flow;Brain;Brain Diseases;Brain imaging;Cause of Death;Chronic;Clinical;clinical application;clinical translation;Clinical Treatment;Clinical Trials;cognitive function;comorbidity;Contingent Negative Variation;Control Groups;Data;Dementia;Deterioration;Development;disability;Disease;Disease Progression;drinking water;Early treatment;effective therapy;Electrophysiology (science);excitotoxicity;experience;experimental study;Failure;FDA approved;Female;Glutamates;high risk;Hour;human old age (65+);Hyperactivity;improved;Individual;Infarction;Inflammation;Inflammatory;innovation;Investigation;Ischemia;Ischemic Stroke;male;Mediating;Medical;Memantine;Memory;mild cognitive impairment;military veteran;Molecular;Monitor;mouse model;Mus;N-Methyl-D-Aspartate Receptors;Nervous System Disorder;neural network;Neurodegenerative Disorders;neuron loss;Neurons;neuroprotection;Neuroprotective Agents;neurovascular;neurovascular unit;NMDA receptor antagonist;novel;novel therapeutics;Older Population;Outcome;Pathogenicity;Pathology;Pathway interactions;Patients;Pharmaceutical Preparations;Physiological;Population;post stroke;post stroke cognitive impairment;post stroke dementia;post stroke depression;pre-clinical research;preconditioning;Predisposition;Preventive treatment;Process;protective effect;psychologic;Reaction;receptor;Recommendation;Recovery;regenerative;Reporting;Research;Risk Factors;Safety;sham surgery;Signal Transduction;Slice;Social Behavior;Stage Grouping;Stroke;stroke model;stroke patient;stroke risk;symptom treatment;Symptoms;Synaptic plasticity;tau Proteins;Testing;Therapeutic;therapeutic target;Time;translational potential;Veterans

PROJECT_TITLE: Innovative memantine therapy for neuroprotective effects against ischemic stroke and Alzheimer's disease

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_DEPT: NEUROSCIENCES

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Interneuron dysfunction is strongly associated with autism, schizophrenia and childhood epilepsy. Increasing experimental evidence points towards imbalances between the excitatory and inhibitory circuits in the brain as a prominent component in the etiology of these illnesses. This project is aimed at further our understanding on how electrical activity affects early brain maturation during critical periods of development with an emphasis on inhibitory neurons.

PI_NAMEs: DE MARCO GARCIA, NATALIA VANESA (contact);RAJADHYAKSHA, ANJALI M

PROGRAM_OFFICER_NAME: KISHORE, SANDEEP

PROJECT_TERMS: Ablation;Adult;Affect;Alleles;Apoptosis;attenuation;autism spectrum disorder;barrel cortex;Behavior;Behavioral;behavioral impairment;Bipolar Disorder;Brain;brain abnormalities;Calcium;Cell Death;Cerebral cortex;childhood epilepsy;clinically relevant;critical period;Data;Defect;Development;Disease;Electroporation;Emergency Situation;Ensure;Equilibrium;Etiology;Event;excitatory neuron;experimental study;Functional disorder;gamma-Aminobutyric Acid;Genes;Genetic;genetic approach;Goals;high risk;Image;Impairment;in utero;in vivo;in vivo calcium imaging;inhibitory neuron;innovation;Interneurons;Knowledge;L-Type Calcium Channels;Laser Scanning Microscopy;Lead;maladaptive behavior;Medial;Mediating;Mus;mutant;Mutation;neonate;Neurodevelopmental Disorder;Neurons;neuropathology;novel;optogenetics;Outcome;Output;Parvalbumins;Patients;Pattern;Phenotype;postnatal;postnatal development;Process;programs;pup;Pyramidal Cells;receptor;Regulation;Research;response;Role;Schizophrenia;Sensory;Shapes;Signal Pathway;Signal Transduction;Slice;Somatostatin;Source;Stimulus;Study models;Synapses;Tactile;Techniques;Testing;Timothy syndrome;translational impact;two-photon;Vibrissae;Work

PROJECT_TITLE: GABAergic Interneuron Dysfunction in Developing Cortical Circuits Underlying Autism Spectrum Disorders


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases;Lymphatic Research;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAN FRANCISCO

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Endothelial cells are known to aid in stem cell maintenance and regeneration in many tissues, but little is known about the role of endothelial cells, particularly lymphatic endothelial cells in the intestinal niche. Additionally, how lymphatic endothelial cells in the small intestine change in chemotherapy induced mucositis and how these changes relate to epithelial repair, remains unknown. My proposed work aims to understand how lymphatic endothelial cells, in part through the expression of the WNT modulators RSPO3 and WLS, contribute to ISC regeneration after cytotoxic injury.

PI_NAMEs: PALIKUQI, BRISA  (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Adult;Affect;Apoptosis;Automobile Driving;Blood;Blood Vessels;Cancer Patient;cancer therapy;cell behavior;Cell Line;Cell Maintenance;cell regeneration;cell type;Cessation of life;chemotherapy;comparison control;Comprehension;cytotoxic;Data;differential expression;Endothelial Cells;Enteral;Epithelial Cells;epithelial repair;Epithelium;Exhibits;Fluorouracil;Genetic Transcription;Goals;Health;Inflammatory;Injury;intestinal injury;Intestines;Knock-out;Knockout Mice;Knowledge;Lymph;Lymphatic;Lymphatic Endothelial Cells;lymphatic vessel;Malnutrition;Metabolic;Modeling;mouse model;Mucositis;Mus;Natural regeneration;novel;Outcome;paracrine;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Play;Plumbing;Process;Proliferating;Radiation;Recovery;repaired;response;Role;self-renewal;Signal Transduction;Signaling Molecule;single-cell RNA sequencing;Small Intestines;Sodium Dextran Sulfate;stem cell division;stem cell expansion;stem cell function;stem cell niche;stem cell self renewal;stem cells;Study models;Testing;Therapeutic;therapeutic target;Tissues;WNT Signaling Pathway;Work

PROJECT_TITLE: Assessing the role of lymphatic endothelial cell niche in intestinal regeneration


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Narrative The goal of this applications is to characterize in detail the mechanism by which three proteins that we discovered to bind to the HIV genome regulate up or down HIV expression. Drugs that can manipulate HIV expression from infected cells have immense potential in functional cure approaches. The more knowledge we gain on the how these host proteins interact with viral proteins and regulate HIV, the more we can leverage host regulators as antiviral targets.

PI_NAMEs: VALENTE, SUSANA T (contact)

PROGRAM_OFFICER_NAME: SHANKAR, UDAY K

PROJECT_TERMS: Acceleration;acrosome stabilizing factor;Affect;Affinity Chromatography;antiretroviral therapy;Automobile Driving;Binding;Binding Proteins;Biological;CD4 Positive T Lymphocytes;Cell model;Cells;Cellular Metabolic Process;ChIP-seq;Chromatin;Chromatin Remodeling Factor;Chromatin Structure;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;cortistatin;Dependence;detection limit;Elements;Environment;Epigenetic Process;epigenetic silencing;ERCC3 gene;follow-up;Generic Drugs;Genes;Genetic Transcription;Goals;Heterochromatin;HIV;HIV Genome;HIV-1;Impairment;In Vitro;in vivo;in vivo Model;Individual;inhibitor;insight;Integration Host Factors;Interruption;knock-down;Knock-out;Knowledge;Link;Mass Spectrum Analysis;Mediating;Messenger RNA;Modification;Molecular;Molecular Conformation;novel;Nucleosomes;overexpression;Pathway interactions;Pharmaceutical Preparations;Positioning Attribute;Post-Translational Protein Processing;Productivity;prohibitin;Proliferating;promoter;protein complex;Proteins;Proviruses;reactivation from latency;recruit;Reporting;Reproducibility;Residual state;RNA Polymerase II;RNA Splicing;Role;small hairpin RNA;small molecule;Spironolactone;targeted agent;Testing;Transactivation;Transcription Coactivator;transcription factor;transcription factor TFIIH;transcriptomics;Translational Protein Modification;Viral;Viral Proteins;viral rebound;Viremia

PROJECT_TITLE: Host factors regulating HIV latency and reactivation

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Tumor cells display nuclear pore and chromosomal defects, however, their specific mechanistic contribution to cancer progression is ill-defined. To enable the dissection of these intricate biological processes and their contribution to the aggressiveness of prostate cancer, our laboratory interrogates in vitro and in vivo patient- derived experimental models via transcriptomic, high-resolution live imaging microscopy, biochemistry and genetic approaches combined with publicly available patient datasets evaluation and patient tumor tissue validation. Our studies aim to identify novel actionable nuclear pore-regulated mechanisms in lethal prostate cancer that may benefit the clinical management of therapy refractory disease.

PI_NAMEs: RODRIGUEZ-BRAVO, VERONICA  (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Address;Advanced Development;advanced prostate cancer;Anaphase;Androgen Receptor;aurora B kinase;Automobile Driving;Binding;Biochemical;Biochemistry;Biological Assay;Biological Process;Cancer Patient;Carcinoma;Castration;Cell Death;Cell Survival;Cells;Chemoresistance;Chromatin;Chromosome abnormality;Clinical;clinical development;clinical efficacy;Clinical Management;clinically relevant;clinically significant;cofactor;cohort;Computer Analysis;Coupled;Cytogenetic Analysis;Data;Data Set;Defect;Development;Disease;Dissection;efficacy evaluation;efficacy testing;Epigenetic Process;Evaluation;Experimental Models;functional genomics;Future;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;Genes;Genetic;genetic approach;Genetic Transcription;Genome;genome integrity;Genome Stability;Genomic approach;Goals;high resolution imaging;Human;human disease;Immunohistochemistry;Importins;improved;In Vitro;in vitro Model;in vivo;inhibitor;inner centromere protein;innovation;Laboratories;Link;live cell imaging;Malignant neoplasm of prostate;Malignant Neoplasms;Metastatic Prostate Cancer;microscopic imaging;Microscopy;Mitosis;Mitotic;Mitotic Activity;Mitotic Checkpoint;Modeling;Molecular Target;neoplastic cell;novel;novel marker;novel therapeutic intervention;Nuclear Pore;Nuclear Pore Complex;Nuclear Pore Complex Proteins;nucleocytoplasmic transport;Oncogenic;Organoids;Outcome;Pathogenesis;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Phosphotransferases;Post-Translational Protein Processing;pre-clinical;Pre-Clinical Model;predictive marker;prevent;Production;Proliferating;Property;Prostate;prostate cancer cell;prostate cancer model;prostate cancer progression;Prostate Cancer therapy;Prostatic Neoplasms;Protein Isoforms;Proteomics;Publishing;Receptor Cross-Talk;Receptor Signaling;Refractory;Refractory Disease;Regulation;Research Proposals;Resistance;Resolution;response;Role;Sampling;Solid Neoplasm;Testing;Therapeutic Intervention;therapy resistant;Tissue Sample;transcription factor;Transcriptional Regulation;transcriptomics;tumor;tumor progression;Tumor Tissue;tumorigenesis;Up-Regulation;Validation;Variant;Work

PROJECT_TITLE: Role of Nuclear Pore-Regulated Mechanisms in Prostate Cancer Aggressiveness

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Cancer;Clinical Research;Prostate Cancer;Urologic Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

PHR: Narrative/Relevance  Castration-resistant prostate cancer is the lethal form of prostate cancer and the second leading cause of cancer death for men in the United States. This proposal will elucidate metabolic mechanisms that enable resistance to potent androgen receptor antagonist therapies. We anticipate that the insights gained from this proposal will directly lead to the identification of new drug targets and the development of improved treatment strategies for more effective clinical therapy.

PI_NAMEs: SHARIFI, NIMA  (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Ablation;advanced prostate cancer;Agonist;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;androgen sensitive;Androgens;antagonist;AR gene;Cancer Etiology;Castration;Cessation of life;Clinic;Clinical;clinical application;cofactor;Data;Development;enzalutamide;enzyme activity;Enzymes;Generations;Genes;Glucocorticoid Receptor;Glucocorticoids;Growth;Hexoses;hormone therapy;Human;Hydrocortisone;Hydroxysteroid Dehydrogenases;improved;inorganic phosphate;insight;Ligands;Malignant neoplasm of prostate;Mediating;Medical Castration;men;Metabolic;metabolic phenotype;Metabolism;Metastatic Prostate Cancer;Molecular;Neoplasm Metastasis;new therapeutic target;next generation;novel therapeutic intervention;Oxidoreductase;Pathway interactions;Patients;pharmacologic;protein degradation;protein expression;Proteins;Receptor Up-Regulation;receptor upregulation;reconstitution;Recurrence;Resistance;resistance mechanism;response;restoration;standard of care;Stanolone;targeted agent;Testosterone;Therapeutic;Therapeutic Effect;therapeutic target;treatment strategy;tumor;tumor metabolism;tumor progression;Tumor Tissue;United States;Up-Regulation;Work

PROJECT_TITLE: Aberrant tumor metabolism that enables AR antagonist-resistant prostate cancer

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: SYRACUSE

ORG_DEPT: BIOLOGY

ORG_NAME: SYRACUSE UNIVERSITY

PHR: PROJECT NARRATIVE: De novo tissue morphogenesis is a fundamental process that contributes to building and maintaining organs, as well as orchestrating overall embryogenesis. This project will determine the mechanisms behind lumen formation and the role of cytokinesis/abscission in this process. Specifically, we will determine whether the site of abscission provides a landmark to initiate polarity and cilia formation through directed vesicle transport.

PI_NAMEs: HEHNLY, HEIDI  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Ablation;Address;Apical;apical membrane;Attention;Biology;Cardiac;Cell Cycle;Cell Differentiation process;Cell division;Cell membrane;Cell Nucleus;Cells;Cellular biology;Centrosome;Cilia;ciliopathy;cilium biogenesis;cilium motility;Congenital Heart Defects;Cyst;Cystic Fibrosis Transmembrane Conductance Regulator;Cytokinesis;Cytosol;daughter cell;Defect;Development;Developmental Biology;Embryonic Development;Epithelial Cells;epithelial to mesenchymal transition;Epithelium;Event;Excision;fluid flow;Genes;Hair;Heart;Human;In Vitro;in vivo;Kidney;kinetosome;Lasers;Left;Link;Liver;Membrane;Membrane Protein Traffic;Mesenchymal;Mesenchymal Stem Cells;Microtubules;Mitosis;model organism;Modeling;Molecular;Morphogenesis;optogenetics;Organ;Organelles;Pancreas;Pathway interactions;Patients;Pattern;Play;PLK1 gene;Positioning Attribute;precursor cell;premature;Process;protein expression;Publications;Resolution;Role;Signal Transduction;Site;System;Testing;Time;Tissues;trafficking;Vertebrates;Vesicle;vesicle transport;Visualization;Work;Zebrafish

PROJECT_TITLE: Cell cycle dependent mechanisms triggering lumen formation in vivo

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Mental Health;Pediatric

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: PROJECT NARRATIVE This pilot clinical trial leverages novel, scalable, and sustainable mobile technology, applied as an adjunct to behavioral treatment, to enhance real time skills utilization and promote sustained improvement for adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). This research will provide valuable data toward understanding how technology can optimize skills engagement, promote adherence, and improve treatment response in adolescents, which has the potential to critically inform treatment research with wide- reaching applications for other skills-based and behavioral treatments.

PI_NAMEs: DVORSKY, MELISSA RENEE (contact)

PROGRAM_OFFICER_NAME: SIMS, BELINDA ENITA

PROJECT_TERMS: acceptability and feasibility;adaptive intervention;Address;Adherence;Adolescence;Adolescent;Adult;Affect;Aftercare;Age;Attention;Attention deficit hyperactivity disorder;Award;behavior change;Behavior Therapy;Behavioral;California;care costs;career;career development;Caring;Childhood;Clinical Sciences;Clinical Trials;cognitive process;cognitive system;Compensation;computer human interaction;contingency management;Data;design;Development;Development Plans;digital;digital health;digital tool;digital treatment;Effectiveness;effectiveness trial;empowerment;Enhancement Technology;Evaluation;evidence base;Executive Dysfunction;executive function;experience;Family;Feedback;Financial Hardship;Focus Groups;follow-up;forgetting;Functional impairment;Funding;Future;Goals;Grant;Health Personnel;Health Technology;Hyperactivity;Impairment;improved;in vivo;innovation;interactive tool;Intervention;intervention effect;intervention refinement;Intervention Trial;Interview;Laboratories;Learning;Life;Maintenance;Mechanics;Mental disorders;Mental Health;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methods;mobile computing;Modality;Monitor;Motivation;National Institute of Mental Health;novel;Outcome;Parents;Pathway interactions;Performance;personalized strategies;Phase;Positioning Attribute;Positive Valence;Process;programs;Protocols documentation;Provider;Psychological reinforcement;Recommendation;reduce symptoms;Research;research data dissemination;Research Personnel;Research Support;Resources;response;reward processing;Rewards;Risk;San Francisco;School Drop-Outs;Schools;Severities;Short-Term Memory;skills;social;Social support;Societies;Strategic Planning;Student Dropouts;substance use;System;Technology;Testing;theories;therapy design;therapy development;Time;tool;Training;Translational Research;treatment adherence;treatment optimization;Treatment outcome;treatment research;treatment response;trial comparing;Universities;usability;user centered design;Validation;Work;Writing;Youth

PROJECT_TITLE: Leveraging Technology to Promote Skill Utilization and Enhance Treatment Outcomes in Young Adolescents with ADHD

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Machine Learning and Artificial Intelligence

PHR: Project narrative Bacteria and fungi have evolved intricate mechanisms to detect their environment and transduce signals across biological membranes, inducing responses in organismal behaviors like growth, survival, and pathogenicity. Despite the prevalence of these transmembrane receptors, our understanding of the discrete mechanisms by which signals are propagated is still evolving. Through protein design and structural biology, we will elucidate the biophysical mechanisms of transmembrane signal transduction, establishing structure-function relationships that help us to better understand how biological systems have evolved to sense the world around them and leave us poised to more effectively target and engineer these signaling mechanisms.

PI_NAMEs: HATSTAT, ANNA KATHERINE (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: Address;Adopted;Algorithms;Area;Bacteria;Behavior;Binding;Biochemical;Biological;Biological Assay;biological systems;Biophysical Process;Biophysics;career;Cells;Chimera organism;Collaborations;Complex;Computational Biology;conformer;Coupling;Cryoelectron Microscopy;Data;Data Collection;data modeling;design;Engineering;Environment;Exhibits;extracellular;Fingerprint;fitness;fungus;generative adversarial network;Genetic Transcription;Goals;Growth;In Vitro;insight;interest;Knowledge;Libraries;Ligand Binding;Ligands;Machine Learning;Membrane;Membrane Proteins;mimetics;Modeling;Molecular;Molecular Conformation;Mutate;neural network algorithm;non-Native;Output;particle;Pathogenicity;Pathway interactions;Phosphorylation;Plants;post-doctoral training;Postdoctoral Fellow;Preparation;Prevalence;Process;Protein Dynamics;Protein Engineering;protein structure;protein-histidine kinase;Proteins;receptor;Receptor Signaling;reconstitution;Research;response;scaffold;sensor;sensor histidine kinase;Signal Transduction;Signal Transduction Induction;skills;Specificity;Stimulus;structural biology;Structure;Structure-Activity Relationship;System;Testing;Thermodynamics;Training;Translating;Universities;Work;X-Ray Crystallography

PROJECT_TITLE: A protein design- and structure-guided interrogation of signal transduction mechanisms


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Prevention

ORG_CITY: AMHERST

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: Narrative Gram-negative ‘superbugs’ have been classified as an urgent threat to public health globally. Recently, strains of Escherichia coli and Klebsiella pneumoniae that are resistant to all antibiotics have emerged and spread worldwide. This highlights the significance of the current project, which aims to devise innovative strategies for combinations of available antibiotics to successfully combat these highly resistant, deadly pathogens.

PI_NAMEs: BULITTA, JURGEN BERND;TSUJI, BRIAN  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Abdominal Infection;Affinity;Antibiotics;Aztreonam;Bacteria;beta-Lactamase;beta-Lactams;Binding;Binding Proteins;Biological Assay;carbapenem resistance;carbapenem-resistant Enterobacteriaceae;carbapenemase;Carbapenems;Ceftazidime;Cell Membrane Permeability;Chromosomes;Classification;Clinic;Clinical;Clinical Trials;colistin resistance;combat;Combined Antibiotics;CRISPR/Cas technology;Data;data integration;Data Set;design;Disease Outbreaks;dosage;Dose;Drug Combinations;Drug Kinetics;Drug resistance;Engineering;Escherichia coli;Extended-spectrum β-lactamase;Face;Fiber;Future;Genetic Engineering;Genomics;global health;Goals;Health;Hospitals;Human;Immune system;Immunocompetent;Impairment;improved;In Vitro;Infection;inhibitor;innovation;insight;Intra-abdominal;Klebsiella pneumoniae;Mediating;Medical;Membrane;Modeling;Molecular;mortality;Mus;Mutation;Nevada;novel;novel strategies;pathogen;Patients;Penetration;Penicillin-Binding Proteins;Permeability;Pharmaceutical Preparations;pharmacodynamic model;Pharmacology;Plasmids;pneumonia model;Polymyxin B;Polymyxin Resistance;Polymyxins;prevent;Prevention;prospective;Public Health;receptor;receptor binding;Regimen;Reporting;Resistance;resistance gene;resistance mechanism;resistant Klebsiella pneumoniae;resistant strain;respiratory;Safety;Sepsis;Site;Superbug;System;Techniques;Testing;Therapeutic;Time;transcriptomics;Translations;Urinary tract;Validation;VDAC1 gene

PROJECT_TITLE: Novel Strategies for Antibiotic Combinations to Combat Gram-negative Superbugs

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


NIH_SPENDING_CATS: Digestive Diseases;Genetics;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_CITY: SAINT LOUIS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: SAINT LOUIS UNIVERSITY

ORG_STATE: MO

PHR: Hepatitis B virus (HBV) chronically infects >250 million people world-wide and kills ~900,000 annually by inducing liver failure or liver cancer, but current therapies are not curative and only partially suppress disease progression. HBV replicates by coordinate action of the viral reverse transcriptase and ribonuclease H (RNaseH) activities, but no anti-HBV RNaseH drugs exist despite the RNaseH being an attractive drug target. Here, we will conduct lead optimization and hit-to-lead medicinal chemistry campaigns to advance development of two related chemotypes of HBV RNaseH inhibitors as novel drug leads for treating chronic HBV infections.

PI_NAMEs: MEYERS, MARVIN J;TAVIS, JOHN E (contact)

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: Active Sites;Advanced Development;analog;anti-hepatitis B;Binding Proteins;Capsid;Cell Nucleus;Chronic;Chronic Hepatitis B;Clinical;cytotoxic;cytotoxicity;design;detection limit;Development;Disease Progression;DNA;DNA biosynthesis;DNA Viruses;DNA-Directed DNA Polymerase;Drug Kinetics;Drug Targeting;experimental study;Genome;Genomics;Hepatitis B Virus;Hepatocyte;HIV;Human;in vivo;inhibitor;Ions;Lead;lead optimization;Liver;Liver Failure;Maintenance;Malignant neoplasm of liver;Measures;Medicine;metalloenzyme;Microsomes;mouse genome;Mus;novel;novel therapeutics;novel virus;Nuclear;pathogenic microbe;Pathway interactions;Patients;Permeability;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Plasma Proteins;pre-clinical;prevent;Recycling;Reverse Transcription;Ribonuclease H;RNA;RNA-Directed DNA Polymerase;screening;Solubility;Specificity;Structure-Activity Relationship;synergism;Testing;Therapeutic Index;Toxicology;Viral;viral DNA;Viral Genome;viral RNA;Viremia;Virion;Virus Inhibitors;Virus Replication

PROJECT_TITLE: Lead optimization of Hepatitis B Virus ribonuclease H inhibitors


NIH_SPENDING_CATS: Anxiety Disorders;Brain Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Pediatric;Prevention;Serious Mental Illness

ORG_DEPT: PSYCHIATRY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative  Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition that causes enormous human suffering and is thought to result from a complex interplay of genetic and the environmental factors. Our goal in this study is to learn more about what precise genetic factors influence an individuals risk for OCD. We propose to do this by resequencing the protein coding portion of the genome in a large number of OCD subjects and matched controls.

PI_NAMEs: GRICE, DOROTHY E (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Adolescent;Affect;analytical method;Area;Attention deficit hyperactivity disorder;autism spectrum disorder;Awareness;Biological;Biology;Bipolar Disorder;case control;cell type;Child;Chronic;Clinical;Code;Collaborations;Collection;comorbidity;Complex;Copy Number Polymorphism;Country;Data;Data Set;Detection;Development;Disease;disorder risk;DNA;DNA Resequencing;Environmental Risk Factor;Etiology;exome;exome sequencing;follow-up;Functional disorder;gene discovery;Gene Dosage;Gene Expression;Genes;Genetic;genetic architecture;Genetic Risk;genetic risk factor;Genetic Variation;Genome;genome-wide;Genotype;Gilles de la Tourette syndrome;Goals;Human;improved;Individual;Inherited;insertion/deletion mutation;Intellectual functioning disability;Knowledge;Learning;Mental disorders;method development;Methods;Molecular;Molecular Target;Neurodevelopmental Disorder;neuropsychiatry;new therapeutic target;non-genetic;Norway;novel;Nucleotides;Obsessive compulsive behavior;Obsessive-Compulsive Disorder;Outcome;Parents;Pathway interactions;Peptide Sequence Determination;phenotypic data;Play;Population;power analysis;Prevention strategy;Price;Proteins;psychiatric comorbidity;Psychiatric Diagnosis;psychiatric genomics;Psychiatrist;Public Health;Publishing;Research;Risk;risk variant;Role;Sampling;Schizophrenia;Site;skills;societal costs;Specificity;Sweden;System;Tic disorder;tic related;transmission process;Variant

PROJECT_TITLE: 1/2 Rare Genetic Variation and Risk for Obsessive Compulsive Disorder

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Depression;Mental Health;Mental Illness;Neurosciences

ORG_CITY: STANFORD

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: STANFORD UNIVERSITY

PHR: An important goal of modern mental health research is finding the neural circuit components and activity patterns that cause psychiatric symptom; a remarkable convergence of new technologies is occurring that may allow a fundamental leap forward in such circuit-level understanding of anhedonia (the loss of reward from experience), a defining symptom in, among other conditions, the disease of major depressive disorder. These technologies include mechanisms for collecting cellular-resolution dynamical information from deep within the brains of freely-moving mammals—and technologies that will allow us to test the causation of anhedonic states. Insight into the circuit dynamics of anhedonia may not only guide development of new, potent, and specific therapies, but will also contribute to our basic understanding of how neural circuit activity patterns give rise to behavior, with potential relevance to many neuropsychiatric diseases such as depression and schizophrenia.

PI_NAMEs: DEISSEROTH, KARL A. (contact)

PROGRAM_OFFICER_NAME: KIM, DOUGLAS SUN-IL

PROJECT_TERMS: 3-Dimensional;Address;adjudication;Anatomy;Anhedonia;Animals;Anorexia Nervosa;Automobile Driving;Back;Behavior;Behavior Control;Behavioral;Behavioral Paradigm;Brain;Brain Diseases;cell type;Cells;cellular targeting;clinical application;clinically significant;Complex;Conflict (Psychology);conflict resolution;Consummatory Behavior;data streams;design;Desire for food;Development;Disease;drinking water;Electric Stimulation;Electrophysiology (science);Etiology;experience;feeding;Food;Foundations;Functional disorder;Goals;hedonic;Human;Hunger;Image;Impairment;insight;interest;Intervention;Laboratory Animals;Lesion;Light;Literature;Major Depressive Disorder;Mammals;Maps;Mediating;Medical;Mental Depression;Mental disorders;Mental Health;Methods;Modeling;Modernization;Molecular;Motivation;Mus;Nature;neural circuit;Neurons;neuropsychiatric disorder;new technology;novel;optical imaging;optogenetics;Organism;Pathologic;Pattern;Process;Property;psychiatric symptom;Regulation;Research;Resolution;Rewards;Satiation;Schizophrenia;Science;social;Social Environment;Speed;Stroke;Symptoms;Technology;Testing;Thirst;Time;Tissues;transcriptomics;virtual;Water;Work

PROJECT_TITLE: Brain-spanning and scale-crossing circuitry mediating drive function and dysfunction

STUDY_SECTION: PMDA

STUDY_SECTION_NAME: Pathophysiological Basis of Mental Disorders and Addictions Study Section[PMDA]


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

ORG_NAME: DREXEL UNIVERSITY

PHR: PROJECT NARRATIVE Vancomycin-resistant enterococci (VRE) have become important causes of hospital-acquired infections and now represent serious threats to public health. The proposed experiments seek to elucidate the molecular mechanism that allows VRE to detect and respond to vancomycin. This information will prove invaluable in rationally developing new antibiotics and antibiotic adjuvants to combat this emerging crisis.

PI_NAMEs: LOLL, PATRICK J (contact)

PROJECT_TERMS: Adjuvant;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Binding;Biochemical;Biological;Biophysics;Cell Wall;Clinical;clinically relevant;combat;Communities;Cytoplasm;design;Detection;Development;drug testing;Elements;Enterococcus;Enzymes;experimental study;Genes;Genetic Transcription;Genotype;Hospitals;Human;Immune;In Vitro;Infection;insight;Length;Lipids;Maps;Membrane;Microbe;Molecular;Nosocomial Infections;novel;Operon;Organism;Outcome;pathogen;Pathogen detection;Pathway interactions;Patients;Phenotype;Phosphorylation;Protein Dephosphorylation;protein-histidine kinase;Proteins;Public Health;Reaction;reconstitution;Refractory;Resistance;resistance gene;sensor;sensor histidine kinase;Signal Transduction;Soil;Stress;Structure;System;Therapeutic;Time;transcription factor;Transcription Initiation;transposon/insertion element;Vancomycin;Vancomycin Resistance;Vancomycin resistant enterococcus;Work;World Health Organization;X-Ray Crystallography

PROJECT_TITLE: Antibiotic Recognition and Signaling in Vancomycin-Resistant Enterococci (VRE)


ORG_CITY: BOSTON

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

ORG_STATE: MA

PHR: Pain is a very common and disabling symptom in Parkinson’s disease, yet it is often untreated. This study will assess the impact of home-based physical and cognitive exercise interventions to reduce pain in this disease. This approach would offer an easily implemented and affordable way to encourage and maintain use of these interventions by patients virtually indefinitely through our remote access technology. The study findings may help VA clinicians provide optimal care for the many veterans with Parkinson’s disease and chronic pain.

PI_NAMEs: SPARROW, DAVID W. (contact)

PROJECT_TERMS: Address;Age Years;Analgesics;Brief Pain Inventory;Caring;chronic pain;chronic pain management;chronic pain patient;Cognition;Cognitive;cognitive function;cognitive training;common symptom;Communities;Complex;Concept Formation;Controlled Study;coping;design;Disabling;disabling symptom;Disease;efficacy evaluation;executive function;Exercise;exercise intervention;exercise training;experience;functional improvement;Future;Guidelines;Health education;Home;improved;Individual;interest;Intervention;intervention effect;intervention program;Mediating;Mediation;Methods;non-motor symptom;Nonpharmacologic Therapy;Pain;Pain interference;Pain management;pain outcome;pain perception;pain reduction;Parkinson Disease;Patients;pharmacologic;Physical activity;Physical Exercise;Physical therapy;Population;Prevalence;primary outcome;programs;Quality of life;Randomized;Randomized, Controlled Trials;Reporting;Research;Role;Safety;Sample Size;Severities;Technology;Telemedicine;Testing;therapy design;Training Programs;Veterans;virtual patient

PROJECT_TITLE: Telemedicine intervention in patients with chronic pain in PD

STUDY_SECTION_NAME: Chronic Medical Conditions & Aging[RRD6]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Childhood Leukemia;Genetics;Hematology;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE There is an urgent need to understand mechanisms that lead to T-cell acute lymphoblastic leukemia (T-ALL) relapse. This proposal will establish the contribution of dormant leukemia-initiating cells to therapy resistance and will determine if targeting the non-canonical WNT receptor RYK can be used to eliminate these cells and prevent T-ALL relapse.

PI_NAMEs: O'CONNOR, KEVIN  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Acute T Cell Leukemia;acute T-cell lymphoblastic leukemia cell;beta catenin;Biological Assay;Calcineurin;Cell Cycle;Cell Physiology;cell regeneration;Cell Separation;Cell surface;Cells;Chemoresistance;chemotherapy;Child;Childhood Acute Lymphocytic Leukemia;Childhood Precursor T Lymphoblastic Leukemia;Data;Databases;Development;Diagnosis;differential expression;Disease;Disease remission;Exhibits;Failure;Foundations;Frequencies;Gene Expression Profile;Genes;genetic signature;Genetic Transcription;Genetically Engineered Mouse;Goals;Hematopoiesis;hematopoietic stem cell quiescence;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Heterogeneity;Human;human disease;Immunophenotyping;Impairment;in vivo;insight;Label;Laboratories;leukemia;leukemia initiating cell;leukemia relapse;leukemia treatment;Leukemic Cell;leukemic stem cell;leukemogenesis;Mediating;Modeling;mouse model;Mus;NOTCH1 gene;overexpression;Parents;Pathway interactions;patient derived xenograft model;Patients;Population;prevent;progenitor;Prognosis;programs;Proliferating;Radiation therapy;receptor;Recurrent disease;Refractory Disease;regeneration potential;Relapse;Reporting;Resistance;Role;Sampling;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Sorting;stem cell function;stem cell population;stem cell proliferation;stem cells;T-Lymphocyte;T-Lymphocyte Subsets;TAL1 gene;targeted treatment;Testing;Therapeutic;therapy resistant;thymocyte;Thymus Gland;transcriptome sequencing;Transgenic Organisms;Transplantation;WNT Signaling Pathway;Work

PROJECT_TITLE: Targeting dormant leukemia-initiating cells in T-cell acute lymphoblastic leukemia


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Colorectal Cancer;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Liver Disease

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: The engineering of living cells and microbes is a transformative approach to cancer therapy, as cells can be genetically programmed to intelligently sense and respond to environments potentially leading to improved safety and efficacy of therapies. However, the vast number of rapidly engineered therapies far outpaces the throughput of animal-based testing regimes, thus creating a major bottleneck for clinical translation. Leveraging synthetic biology tools and a high-throughput bacteria-spheroid platform, the objective of this proposal is to rapidly optimize tumor-homing S. tyhpimurium to express therapeutics locally and specifically in tumors.

PI_NAMEs: DANINO, TAL  (contact)

PROGRAM_OFFICER_NAME: FEHR, TUBA HALISE

PROJECT_TERMS: 3-Dimensional;Acceleration;Animal Model;Animals;anti-cancer;anti-cancer therapeutic;Antitumor Response;Attenuated;Automobile Driving;Bacteria;Biological Assay;Cancer Biology;Cancer Model;cancer therapy;CD47 gene;CD8B1 gene;Cell Death;Cell Line;cell type;Cells;Clinical;clinical translation;Clinical Trials;Coculture Techniques;Colorectal;Colorectal Cancer;colorectal cancer treatment;Combined Modality Therapy;Communities;Cues;Cytolysis;cytotoxicity;Databases;delivery vehicle;Development;Diagnostic;Disease;draining lymph node;effective therapy;effector T cell;efficacy study;Engineering;Environment;Euthanasia;Evaluation;Fluorescence Microscopy;Future;Gene Modified;Genes;Genetic;Genetic Engineering;Genetic Programming;Goals;Growth;Heterogeneity;Histologic;Home;Homing;Human;Human body;Hypoxia;immunogenicity;Immunologic Surveillance;Immunotherapeutic agent;improved;in vivo;in vivo imaging system;Infiltration;interest;lead candidate;Libraries;Liver;Malignant Neoplasms;metastatic colorectal;Metastatic Neoplasm to the Liver;Microbe;microbiome research;Microscopy;Modeling;Molecular;mouse model;Mus;Necrosis;Neoplasm Metastasis;novel;novel therapeutics;Oral;Organ;Pathogenicity;Peptides;Performance;Population;pre-clinical;Prevalence;Production;Proliferating;Reporter;Research;response;Route;Safety;safety assessment;safety study;safety testing;Salmonella typhimurium;screening;Solid Neoplasm;Source;spatiotemporal;Specificity;spheroids;synergism;synthetic biology;System;Testing;Therapeutic;therapeutic evaluation;therapy outcome;Time;Tissues;tool;Toxic effect;Toxin;Treatment Efficacy;tumor;tumor growth;tumor hypoxia;tumor microenvironment;Tumor Tissue

PROJECT_TITLE: Engineering S. typhimurium for metastatic colorectal cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Clinical Research;Endocrine Disruptors;Genetics;Neurodegenerative;Neurosciences;Prevention;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative condition, and environmental exposures are hypothesized to play a role in disease pathogenesis and progression. Our goal is to identify environmental pollutant exposures that contribute to ALS disease risk and survival when accounting for genetic susceptibility to understand how these exposures play a role in ALS pathogenesis. This work will have wide-ranging implications on ALS disease prevention and treatment.

PI_NAMEs: BATTERMAN, STUART A;FELDMAN, EVA LUCILLE (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: absorption;Accounting;Affect;Age;ALS patients;Amyotrophic Lateral Sclerosis;Autopsy;Biological;Biological Monitoring;Body mass index;Brain;Central Nervous System;cohort;comparison control;Complex;Data;demographics;Disease;Disease Progression;disorder prevention;disorder risk;Environment;Environmental and Occupational Exposure;Environmental Exposure;Environmental Monitoring;Environmental Pollutants;Environmental Risk Factor;epidemiologic data;Exposure to;Genes;Genetic;Genetic Predisposition to Disease;Genetic Risk;Geography;Goals;Heavy Metals;Heterogeneity;Hobbies;improved;innovation;insight;interest;Link;Maps;Measurement;Measures;Metabolic;Michigan;Modeling;modifiable risk;Nerve Degeneration;Neurodegenerative Disorders;new therapeutic target;Occupational;Occupational Exposure;Occupations;organochlorine pesticide;organochlorine pesticide exposure;Organophosphates;outreach;Pathogenesis;Patients;Peripheral;persistent organic pollutants;pesticide exposure;Pesticides;Phenotype;Physical activity;pleiotropism;pollutant;polybrominated diphenyl ether;Polychlorinated Biphenyls;polygenic risk score;Population;Predisposition;Public Health;public health intervention;Recording of previous events;recruit;Reporting;repository;Risk;Risk Factors;Sampling;sex;Spinal Cord;Surveys;Testing;Time;Tissues;Toxic Environmental Substances;Toxin;Trace metal;translational impact;Trauma;Universities;uptake;Work

PROJECT_TITLE: Mapping the ALS Exposome to Gain New Insights into Disease Risk and Pathogenesis

STUDY_SECTION: NAME

STUDY_SECTION_NAME: Neurological, Aging and Musculoskeletal Epidemiology Study Section[NAME]


NIH_SPENDING_CATS: Anxiety Disorders;Brain Disorders;Genetics;Human Genome;Mental Health;Mental Illness;Serious Mental Illness

ORG_CITY: RICHMOND

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Narrative This project seeks to clarify the etiology of key internalizing psychiatric disorders and closely associated functional medical disorders by applying a range of methods from epidemiology, genetic epidemiology and molecular genetics to the large informative population-based cohort in the Netherlands called Lifelines. We will attempt to understand the origins of the comorbidity between these disorders and how genes and environment contribute to their development. To meet these goals, we will apply advanced statistical methods to a unique set of epidemiological and molecular genetic resources.

PI_NAMEs: KENDLER, KENNETH SEEDMAN (contact);LOO, HANNA VAN;SCHOEVERS, ROBERT

PROJECT_TERMS: Academic Medical Centers;Adult;Age;age effect;Behavioral Genetics;Blood;Brain;burden of illness;Chronic Fatigue Syndrome;cohort;Cohort Analysis;comorbidity;Data;design;Development;Disease;Dysthymic Disorder;Environment;Environmental Risk Factor;Epidemiologic Methods;Epidemiology;Equation;Etiology;Factor Analysis;Family;family genetics;Family member;family structure;Fibromyalgia;Functional disorder;gene environment interaction;Gene Expression;Generalized Anxiety Disorder;Generations;Genes;Genetic;genetic architecture;genetic epidemiology;genetic resource;genetic risk factor;genome-wide;Genomics;Genotype;Goals;Health;Heterogeneity;improved;Irritable Bowel Syndrome;Joints;Major Depressive Disorder;Measures;Medical;Mendelian randomization;Mental disorders;Methods;microbiome;Modeling;Molecular Genetics;Netherlands;offspring;Panic Disorder;Parents;Pathway interactions;Pattern;Phenotype;polygenic risk score;population based;Principal Investigator;programs;prospective;Psychiatry;psychogenetics;Public Health;Quantitative Trait Loci;Recording of previous events;Research;Risk;Risk Factors;sex;Siblings;Single Nucleotide Polymorphism;Social Phobia;Statistical Methods;Structure;Symptoms;time use;transmission process;Typology;Virginia;Whole Blood

PROJECT_TITLE: An Integrative Approach to the Etiology of Internalizing Disorders in the Lifelines Cohort

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Mental Health;Mental Illness;Neurosciences;Prevention;Serious Mental Illness;Sleep Research;Suicide;Suicide Prevention

ORG_CITY: PROVIDENCE

ORG_NAME: BUTLER HOSPITAL (PROVIDENCE, RI)

ORG_STATE: RI

PHR: Project Narrative Suicidal ideation and suicidal behavior are increasingly serious public health concerns in the United States. We propose the development of a sleep-based, integrated, multi-method model of proximal suicide risk emphasizing near-term and proximal measures of risk and derived from a combination of intensive ecological momentary assessment, digital phenotyping, laboratory-based behavioral assessments, peripheral psychophysiological biomarkers, and cross-sectional measures including clinical interviews and self-report measures.

PI_NAMEs: ARMEY, MICHAEL F (contact);BOZZAY, MELANIE

PROGRAM_OFFICER_NAME: LEITMAN, DAVID ISAAC

PROJECT_TERMS: actigraphy;Acute;Affect;Affective;Algorithms;Arousal;Aviation;Behavior;Behavior assessment;Behavioral;Biological Markers;Cellular Phone;circadian;Clinical;Cognitive;cognitive function;cognitive system;Complex;Coupled;daily functioning;Data;Data Set;Decision Making;Development;digital phenotyping;Distal;Ecological momentary assessment;Effectiveness;Emotional;Emotions;Enhancement Technology;Environment;Equation;Event-Related Potentials;Fatigue;Feeling suicidal;follow up assessment;Future;Goals;heart rate variability;high risk;Hospitals;Hour;Impairment;improved;Impulsivity;indexing;Individual;innovation;Intervention;Interview;Laboratories;Link;Location;Measures;Mental Fatigue;Methods;Mission;Modeling;Motion;negative affect;Neurocognitive;novel;Patient Self-Report;Performance;Peripheral;Persons;Phase;phenomenological models;Phenotype;poor sleep;Population;Populations at Risk;predictive modeling;prevent;Process;prospective;psychiatric inpatient;Psychophysiology;Psychotherapy;Public Health;recruit;reducing suicide;Research Domain Criteria;response;Risk;Risk Factors;rumination;Sampling;sensor;Sleep;Sleep disturbances;sleep pattern;sleep quality;Sleep Wake Cycle;social;social factors;social networking website;Stress;suicidal;suicidal behavior;suicidal risk;Suicide;suicide model;suicide rate;System;Time;trait;United States;Variant

PROJECT_TITLE: Dynamic Impacts of Sleep Disruption on Ecologically Assessed Affective, Behavioral, and Cognitive Risk Factors for Suicide


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: NEW YORK

ORG_DEPT: PHYSIOLOGY

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative Insects are the primary vectors for many pathogens causing human disease and consequently contribute to the death of millions of people annually. Blood-feeding insects locate their human hosts through their exquisitely sensitive olfactory system, but the molecular mechanisms underlying insect odor detection are poorly understood. This project will elucidate the structural basis for modulation of the conserved insect odorant receptor, Orco, providing an inroad to rationally design novel classes of potent repellent chemicals that ward off biting insects and prevent the transmission of insect-borne disease.

PI_NAMEs: RUTA, VANESSA  (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Adopted;Agonist;Anopheles gambiae;Architecture;Behavior;Binding;Biochemical;Biochemistry;Biological Assay;Blood;Cessation of life;Chemicals;Complex;Coupled;Cryoelectron Microscopy;Cues;Culicidae;Data;design;Detection;Development;Disease;disease transmission;disorder control;Drug Design;Environment;Family;feeding;Foundations;Funding;Generations;global health;Goals;Health;Homologous Gene;Human;human disease;Impairment;Insect Bites;Insect Proteins;Insect Repellents;Insect Vectors;Insecta;insight;Ion Channel;Ions;Ligand Binding;Ligands;Lipid Bilayers;Lipids;Malaria;Mediating;Membrane;Membrane Lipids;Modeling;Molecular;Molecular Target;nanodisk;Nature;novel;novel strategies;Odorant Receptors;Odors;Olfactory Pathways;olfactory receptor;pathogen;Pathway interactions;Persons;pharmacologic;Physiological;Play;prevent;Property;protein structure;Proteins;rational design;Reagent;receptor;receptor function;reconstitution;Regulation;Resolution;Role;Route;Signal Transduction;small molecule;Smell Perception;Specificity;stoichiometry;structural determinants;Structure;success;transmission process;vector;virtual;Volatilization;ward;Work

PROJECT_TITLE: Molecular Mechanisms Underlying Insect Odorant Receptor Function and Modulation

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Disability Research;Genetics;Hearing Loss;Human Genome;Neurosciences;Rehabilitation

ORG_CITY: IOWA CITY

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF IOWA

PHR: In Specific Aim 1 of this grant, we will leverage the power of whole genome sequencing and structured bioinformatic analysis to identify novel deafness-associated genes in carefully selected patient cohorts. In Specific Aim 2, we will resolve hidden heritability in known deafness-associated genes by targeted analysis of non-coding regions and select missense and synonymous variants. The completion of these two specific aims will improve the clinical care of persons with hearing loss and provide a foundation for gene therapies that target specific types of genetic deafness.

PI_NAMEs: SMITH, RICHARD J.H. (contact)

PROGRAM_OFFICER_NAME: WATSON, BRACIE

PROJECT_TERMS: Address;Animal Model;Auditory;Bioinformatics;Biology;clinical care;clinical diagnosis;cohort;Complex;deaf;deafness;Development;diagnostic algorithm;Family;Fostering;Foundations;Gene Targeting;gene therapy;gene-targeted therapy;Genes;Genetic;genetic deafness;genetic epidemiology;genetic testing;genetic variant;genome sequencing;Goals;Grant;Haplotypes;hard of hearing;Hearing;hearing impairment;hereditary hearing loss;Heritability;improved;insight;Knowledge;Labyrinth;Molecular;Molecular Target;normal hearing;novel;novel therapeutics;Outcome;Pathogenicity;Patient Selection;Persons;Physiology;Population;precision medicine;Presbycusis;Regulatory Element;Research;Resources;Role;Structure;success;targeted treatment;Technology;Untranslated RNA;Variant;whole genome

PROJECT_TITLE: Non-Syndromic Hearing Loss A Collaborative Study