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

ORG_CITY: EAST LANSING

ORG_DEPT: CHEMISTRY

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: Project Narrative Life-threatening fungal infections occur to more than two million patients annually, with high mortality due to scarcity and limited efficacy of antifungal drugs. The design of novel drugs targeting cell wall biomolecules requires knowledge of their structures and nanoscale assemblies in the native cellular context. We will determine drug-induced structural remodeling of cell walls using living cells of Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans, the three most prevalent fungal pathogens, thus presenting a significant advance in medical mycology research that guides novel antifungal therapeutic strategies.

PI_NAMEs: WANG, TUO  (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Anabolism;anti-fungal agents;Architecture;Aspergillus;Aspergillus fumigatus;beta-Glucans;Biophysics;Biopolymers;Candida;Candida albicans;Candida auris;capsule;carbohydrate structure;Carbohydrates;Cell membrane;Cell Physiology;Cell Wall;Cells;Cellular Structures;Characteristics;Chitin;clinical application;Collection;Cryptococcus;Cryptococcus neoformans;Data;design;Development;Dimensions;Drug Design;Drug Modulation;Drug resistance;drug sensitivity;Drug Targeting;Drug usage;echinocandin resistance;environmental stressor;Family;Fungal Drug Resistance;fungicide;fungus;Genetic Polymorphism;Glucans;Goals;Health;Human;Hydrophobicity;Immune Evasion;Immunocompromised Host;improved;Infection;innovation;insight;Knowledge;Life;Link;mechanical properties;Medical;Melanins;Methodology;Modeling;Molecular;Monitor;mortality;mutant;Mutation;Mycoses;nanoscale;new therapeutic target;nikkomycin;novel;novel therapeutics;Nuclear;Organelles;Osmosis;pathogenic fungus;Pathogenicity;Patients;Performance;Permeability;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Polysaccharides;Positioning Attribute;Predisposition;Process;Production;Publishing;Research;Resistance;resistance mechanism;Resolution;response;Sodium Chloride;solid state nuclear magnetic resonance;Structure;Superbug;targeted agent;targeted treatment;Techniques;Technology;Testing;The science of Mycology;Therapeutic;Toxic effect;Virulence;Water

PROJECT_TITLE: Revealing the Cell Wall Organization of Fungal Pathogens and Structural Responses to Antifungal Drugs Using Cellular Solid-State NMR

STUDY_SECTION: MSFB

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


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Behavioral and Social Science;Building Research Capacity at Institutions with Limited NIH Funding;Neurosciences;Pediatric;Social Determinants of Health

ORG_CITY: SAINT LOUIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROSURGERY

ORG_FIPS: US

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Narrative The future of child and adolescent development and behavioral medicine lies in enhancing the diversity and inclusiveness of the research and clinical workforce. The proposed St. Louis Summer Research Immersion Program in Pediatric Neuroscience (SSRIP) will provide a unique and innovative research training experience to high school students who might not otherwise have access to such opportunities. Thus, this proposed R25 program will `grow the pipeline' for early stage learners for research careers in Pediatric Neuroscience, which has been designated by the NIH/NINDS as a priority area for a diverse workforce.

PI_NAMEs: GURNETT, CHRISTINA  (contact);RICHARDS, LINDA J;STRAHLE, JENNIFER

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Acceleration;Address;Adolescent Development;Affect;Area;Behavioral;Behavioral Medicine;Behavioral Research;Behavioral Sciences;Biomedical Research;Brain Diseases;career;Child Development;Child Health;Child Psychiatry;Childhood;Clinical;Clinical Research;Cognitive;college;Communities;community engagement;Creativeness;Development;Disparity;disparity elimination;Diverse Workforce;diversity and inclusion;Education;Education Projects;education research;educational atmosphere;Educational Curriculum;Ensure;Equity;equity, diversity, and inclusion;experience;Exposure to;Faculty;faculty research;Fostering;Funding;Funding Opportunities;Future;Goals;graduate student;Grant;hands-on learning;health disparity;health equity;High School Student;Immersion;Individual;Inequity;Infrastructure;innovation;Institution;interest;Knowledge;Laboratories;Lead;Leadership;Lifelong disability;Literature;matriculation;medical schools;Medical Students;Mentors;Mentorship;Methods;Minority Groups;Mission;Modeling;National Institute of Neurological Disorders and Stroke;neurobehavioral;Neurologic;Neurology;Neurosciences;Neurosciences Research;neurosurgery;outreach;Participant;Prevention;programs;Reproducibility;Research;Research Methodology;Research Personnel;Research Priority;Research Project Grants;Research Technics;Research Training;Resources;Scholars Program;Science;Scientific Inquiry;Scientist;Series;skills;social;social health determinants;Structure;Students;summer program;summer research;symposium;synergism;Talents;Training;Training Programs;undergraduate student;Underrepresented Populations;Underrepresented Students;underserved community;United States National Institutes of Health;Universities;virtual;Washington;work-study;Writing


ADMINISTERING_IC: ES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Biotechnology;Conditions Affecting the Embryonic and Fetal Periods;Endocrine Disruptors;Genetics;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: PROJECT NARRATIVE Spontaneous preterm birth is a highly significant but understudied perinatal outcome that comprises the majority of premature births and has been linked to prenatal exposure to environmental chemicals, including phthalates. This study will investigate the mechanistic link between prenatal phthalate exposure, placental dysfunction, and spontaneous preterm birth using multi-omics data generated in the placenta. Findings from this study will inform chemical toxicological risk assessment and policy, as well as aid in the development of potential biomarkers of spontaneous preterm birth.

PI_NAMEs: PAQUETTE, ALISON GENEVIEVE (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: absorption;Address;Assessment tool;Big Data;Biological Markers;Black race;Chemicals;Circulation;Clinical;cohort;Computational Biology;Data;Data Set;Development;Endocrine Disruptors;Environment;environmental chemical;Environmental Exposure;Epidemiology;epidemiology study;Etiology;Exposure to;Fatty Acids;Functional disorder;Future;Gene Expression;General Population;Genes;Goals;Health;High Prevalence;high risk;in utero;Inflammation;innovation;insight;knowledge translation;Length;Link;Mediating;Mediation;Medical;Medical Research;Messenger RNA;Metabolic Pathway;Metabolism;MicroRNAs;Minerals;modifiable risk;Molecular;Molecular Profiling;mRNA sequencing;Multiomic Data;multiple omics;National Institute of Environmental Health Sciences;neonatal morbidity;Neonatal Mortality;notch protein;novel;Outcome;Overlapping Genes;Participant;Pathway Analysis;Pathway interactions;perinatal outcomes;phthalates;Physiological;Placenta;Policies;Population;potential biomarker;Pregnancy;Pregnancy Trimesters;Pregnant Women;Premature Birth;prenatal;prenatal exposure;Public Policy;repaired;Research;Risk;Risk Assessment;Risk Factors;Role;Sampling;Second Pregnancy Trimester;Signal Transduction;Steroid biosynthesis;targeted treatment;Therapeutic Intervention;Third Pregnancy Trimester;Toxic effect;Toxicology;Transcriptional Regulation;transcriptomics;Underrepresented Populations;urinary

PROJECT_TITLE: Assessing how Prenatal Phthalate Exposure Disrupts Placental Transcriptional Regulation and Contributes to Changes in Gestational Length


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurosciences;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative Latino adolescents consume and misuse alcohol earlier than their peers, placing them at greater risk for developing addiction, health, and mental health problems across their lifetime. The current project examines how several biological and environmental factors work together to increase the risk of alcohol use and misuse in Latino adolescents. Results from this project will allow for the identification of high-risk adolescents and provide broader targets for alcohol use disorder prevention.

PI_NAMEs: ZHEN-DUAN, JENNY  (contact)

PROGRAM_OFFICER_NAME: BALAKATHIRESAN, NAGARAJA SETHURAMAN

PROJECT_TERMS: abuse neglect;addiction;Adherence;Adolescent;adverse childhood events;Affect;Alcohol abuse;Alcohol consumption;Alcohol dependence;alcohol epidemiology;alcohol misuse;alcohol risk;alcohol use disorder;Alcoholism;Alcohols;Area;Award;binge drinking;Biological;biological adaptation to stress;Biological Factors;Biological Markers;biological systems;Biometry;biopsychosocial;career;Child;Childhood;childhood adversity;Chronic;Clinical;cohesion;Collection;Communities;Consumption;cultural values;culturally appropriate intervention;Data;Data Analyses;Data Collection;Discrimination;disorder prevention;Disparity;DNA Methylation;Drug usage;Endocrine;Endocrinology;Ensure;Environmental Risk Factor;Epigenetic Process;ethnic minority;Etiology;Event;experience;Exposure to;Family;Fortification;Foundations;Future;Genes;Genetic;Goals;Hair;Health;Health Disparities Research;Heavy Drinking;High Prevalence;high-risk adolescents;Hostility;Hydrocortisone;hypothalamic-pituitary-adrenal axis;Immigrant;Intervention;Knowledge;Latino;Latino Population;Link;maltreatment;Measures;Mediating;Mental Health;Mentors;Mentorship;Methylation;Minority;Modeling;National Institute on Alcohol Abuse and Alcoholism;National Institute on Minority Health and Health Disparities;Neurobiology;Parents;Participant;Pathway interactions;Patient Self-Report;peer;Pharmacological Treatment;Prevention;Prevention Research;prospective;protective factors;psychologic;Psychologist;psychosocial;racial minority;Research;Research Personnel;resilience;Resources;Risk;Role;Saliva;Sampling;Scientist;social;social culture;sociocultural determinant;Stress;stressor;Structure;substance use;Substance Use Disorder;System;Testing;Time;Training;Work

PROJECT_TITLE: Adverse childhood experiences and alcohol misuse in Latino adolescents: testing biopsychosocial and cultural mechanisms.

STUDY_SECTION: AA

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Precision Medicine;Rare Diseases

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative Finding the most effective therapies for cancer patients is critically dependent on having detailed genomic and molecular insights into the cancer, which currently is only possible by tissue biopsy. Using multiple myeloma as an example of an incurable cancer we are seeking to demonstrate that liquid biopsy of circulating cancer cells and cell-free DNA can replace tissue biopsy and additionally yields clinically actionable information to inform treatment decisions. In this project, we will employ innovative technologies with the goal to establish multimodal liquid biopsy as a comprehensive longitudinal biomarker and practice-changing standard that eliminates the need for tissue biopsy.

PI_NAMEs: LOHR, JENS G (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Affect;Biological Markers;Biopsy;Blood;Bone Marrow;Bone marrow biopsy;Bone Marrow Involvement;burden of illness;Cancer Patient;Caring;cell free DNA;Cells;circulating cancer cell;Clinical;clinical care;clinical decision-making;clinically actionable;clinically relevant;cohort;Databases;Detection;Detection of Minimal Residual Disease;Diagnosis;Disease;Disease Marker;DNA;Drug resistance;Drug resistance pathway;Drug Targeting;effective therapy;Evolution;exome;experience;experimental study;Failure;Genetic;Genetic Diseases;genetic predictors;genetic variant;genome sequencing;genomic predictors;Genomics;Goals;Guidelines;Hematological Disease;Heterogeneity;Immunotherapy;innovative technologies;insight;liquid biopsy;Malignant Neoplasms;Methods;Molecular;molecular dynamics;Monitor;multimodality;Multiple Myeloma;National Comprehensive Cancer Network;Nature;Neoplasm Circulating Cells;Newly Diagnosed;novel;novel strategies;optimal treatments;Outcome;outcome prediction;Patients;Performance;Plasma Cells;Principal Investigator;prognostic;prognostication;Proxy;Recommendation;Recurrent disease;Refractory;Relapse;relapse prediction;Residual Neoplasm;Resolution;response;Risk;Risk Reduction;Sampling Biases;Sensitivity and Specificity;Site;Source;standard of care;success;survival prediction;targeted sequencing;Technology;Testing;Therapeutic;Time;Tissues;treatment choice;treatment response;United States National Institutes of Health;Variant;whole genome;Writing

PROJECT_TITLE: Liquid biopsy in myeloma to inform outcome and treatment decisions

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Digestive Diseases;Genetics;Liver Cancer;Liver Disease;Orphan Drug;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: We seek to identify novel connections between metabolism and DNA repair in human cancers. We have discovered that mutations in genes associated with metabolism that are either inherited or occur in cancers confer a DNA repair deficiency and a previously unexpected vulnerability to the class of anti-cancer agents called PARP inhibitors. In the proposed work, we will uncover new connections between metabolism and DNA repair in human cells and develop new ways to treat metabolism-driven cancers in a targeted manner to advance effective new therapies.

PI_NAMEs: GLAZER, PETER M (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Acceleration;Acute Myelocytic Leukemia;Alcohol dehydrogenase;alpha ketoglutarate;Antineoplastic Agents;BCL2 gene;Biological Assay;branched-chain-amino-acid transaminase;BRCA1 Mutation;BRCA2 Mutation;cancer cell;Carcinogenesis Mechanism;Cells;CHEK1 gene;Cholangiocarcinoma;Chromatin;Citrate (si)-Synthase;Citric Acid Cycle;Clinic;Clinical;clinical development;Clinical Trials;clinically relevant;Colorectal Cancer;Data;design;Dioxygenases;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Repair Disorder;DNA Repair Gene;efficacy study;efficacy testing;Enzymes;Fumarate Hydratase;Fumarates;Funding;Future;Gene Expression;Genes;Genetic;Genetic Transcription;Genome;Genomic Instability;Germ-Line Mutation;Glioma;Grant;Health;Hereditary Leiomyomatosis and Renal Cell Cancer;Hereditary Malignant Neoplasm;Hereditary Neoplastic Syndromes;Hereditary Paraganglioma;histone methylation;Histones;HTATIP gene;Human;Hypermethylation;in vivo;Inherited;inhibitor;Iron;Isocitrate Dehydrogenase;Knowledge;Link;Lysine;Malate Dehydrogenase;Malignant Neoplasms;malignant stomach neoplasm;Mammary Neoplasms;Masks;Melanoma;Metabolic;Metabolic Pathway;Metabolism;Mitochondria;Modeling;Mus;mutant;Mutate;Mutation;Nature;novel;novel therapeutic intervention;novel therapeutics;overexpression;Paraganglioma;Pheochromocytoma;Poly(ADP-ribose) Polymerase Inhibitor;Polymerase;pre-clinical;preclinical study;Primary carcinoma of the liver cells;Proteins;Publishing;rational design;recruit;Renal Cell Carcinoma;repaired;response;Sarcoma;Signal Transduction;small molecule;Stomach Carcinoma;Succinate Dehydrogenase;Succinate-CoA Ligases;Succinates;Syndrome;synergism;targeted agent;Testing;Therapeutic;Translating;translational medicine;Translational Research;tumor;Vorinostat;Work

PROJECT_TITLE: Oncometabolites, DNA Repair, and Cancer

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics;HIV/AIDS;Hematology;Immunotherapy;Infectious Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Our goal is to further develop a simple in vivo approach for durable HIV prophylaxis and therapy. Our approach requires only intravenous injections and could be provided as an outpatient treatment. Using in mouse and non-human primate models, we will also address current biological barriers to achieving an HIV cure

PI_NAMEs: KIEM, HANS-PETER ;LIEBER, ANDRE MICHAEL (contact)

PROGRAM_OFFICER_NAME: POON, BETTY

PROJECT_TERMS: Address;Adenoviruses;AIDS therapy;Ambulatory Care;Animals;anti-viral efficacy;B-Lymphocytes;base editor;Berlin;Biological;Biological Models;Blood;Blood Cells;Bone Marrow;Bone Marrow Purging;Brain;Carmustine;CCR5 gene;CD46 Antigen;Cell Lineage;Cells;cellular transduction;chimeric antigen receptor;Clinical;Complex;conditioning;cost;cost efficient;CXCR4 gene;Developing Countries;disease model;Drug Kinetics;Effector Cell;Erythroid Cells;Escape Mutant;expression vector;gene therapy;Gene Transfer;gene transfer vector;Genes;genome editing;Goals;gutless adenoviral vector;Hematopoiesis;Hematopoietic Stem Cell Mobilization;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Hemoglobinopathies;Hemophilia A;High Dose Chemotherapy;HIV;HIV therapy;HIV/AIDS;Homing;Human;humanized mouse;Hyperactivity;IL8RB gene;Immune;immunogenicity;Immunotoxins;In Vitro;in vivo;Infection;Intravenous;intravenous injection;Knock-out;knockout gene;London;Macaca mulatta;Macrophage;Methylation;Microglia;Modeling;mouse model;Mus;New York;nonhuman primate;Patients;peripheral blood;Pharmaceutical Preparations;portability;Preparation;prevent;prime editor;promoter;Prophylactic treatment;Protocols documentation;receptor;Regimen;Resistance;Risk;Safety;safety testing;side effect;simian human immunodeficiency virus;SIV;Sleeping Beauty;Spleen;stem cell gene therapy;Stream;System;T-Lymphocyte;targeted treatment;Terminator Codon;Testing;Tissues;Toxic effect;trafficking;transgene expression;Transgenes;Transgenic Organisms;Transposase;vector;Viral reservoir;Virulent;Virus

PROJECT_TITLE: In vivo HSC gene therapy using a multi-modular HDAd vector for HIV cure


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Diabetes;Neurosciences;Nutrition;Social Determinants of Health;Tobacco;Tobacco Smoke and Health

ORG_CITY: DETROIT

ORG_DEPT: BIOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: NARRATIVE Type 2 diabetes (T2D) is among the most common and costly challenges confronting modern society. Benzene, one of the major components of air pollution has been found capable of inducing oxidative stress and inflammatory responses, which, may affect insulin resistance (IR), leading to whole-body metabolic imbalance and T2D. To understand the etiology of metabolic disorders, including obesity and T2D, it is essential that we gain insight into the mechanisms by which benzene can cause metabolic imbalance.

PI_NAMEs: SADAGURSKI, MARIANNA  (contact)

PROJECT_TERMS: Ablation;Affect;Age;Air Pollution;Astrocytes;Attention;Benzene;Benzene Exposure;biological adaptation to stress;blood glucose regulation;Cells;Chronic;conditional knockout;cost;design;Detergents;Development;Dose;e-cigarette aerosols;endoplasmic reticulum stress;Energy Metabolism;Environment;Environmental and Occupational Exposure;Environmental Exposure;Etiology;exhaust;exposure route;Exposure to;exposure to cigarette smoke;Food;Future;General Population;Genetic;glial activation;Glucose;glucose metabolism;glucose monitor;Goals;Health;Health Policy;Histology;Homeostasis;Human;human model;Hyperglycemia;Hypothalamic structure;Immune;immunological status;Impairment;In Situ Hybridization;In Vitro;in vivo;Individual;Inflammation;Inflammatory;Inflammatory Response;insight;Insulin;Insulin Resistance;insulin signaling;Intervention;Knockout Mice;Leptin;Link;Literature;LoxP-flanked allele;male;Mediating;Meta-Analysis;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolism;Microglia;Modeling;Modernization;Molecular;Morphology;mouse model;Mus;Neuroglia;neuroinflammation;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Occupational;Outcome;Oxidative Stress Induction;Paint;Pathology;Pathway interactions;Peripheral;Physiological;Pollution;Predisposition;Pregnant Women;prevent;Public Health;Publishing;Regulation;Research;response;Risk;Rodent;Role;Shapes;Signal Pathway;Signal Transduction;Societies;System;systemic inflammatory response;Testing;Time;Tissues;Tobacco smoke;Underrepresented Minority;urban area;urinary;volatile organic compound;Water;Work;young adult

PROJECT_TITLE: Benzene exposure promotes neuroinflammation and metabolic dysregulation

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Neurosciences;Rare Diseases

ORG_CITY: BINGHAMTON

ORG_NAME: STATE UNIVERSITY OF NY,BINGHAMTON

ORG_STATE: NY

PHR: PROJECT NARRATIVE We plan to establish how the bi-directional transport of the nucleus is orchestrated, which is important for normal brain and muscle development. Human disease mutations of proteins participating in the transport of the nucleus cause severe brain and muscle developmental defects, including amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia and spinal muscular atrophy, which is the most common genetic cause of death in infants. Results will establish regulatory mechanisms for dynein and kinesin-1-dependent transport, which can be targeted to treat these devastating neuromuscular diseases.

PI_NAMEs: SOLMAZ, SOZANNE R (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Adaptor Signaling Protein;Affect;Affinity;alpha helix;Amyotrophic Lateral Sclerosis;Binding;Biochemical;Biological Assay;Biological Models;biophysical techniques;Biophysics;Brain;Calorimetry;Cause of Death;Cell Cycle;Cell Cycle Regulation;Cell Nucleus;cell type;Cells;Chromosome Segregation;Collaborations;Complex;crosslink;Cytoplasm;Data;Defect;Development;Disease;Drosophila genus;dynactin;Dynein ATPase;Event;G2 Phase;Genetic;Hereditary Spastic Paraplegia;human disease;improved;Infant Mortality;insight;interdisciplinary approach;Kinesin;kinetic model;Length;Link;Methods;Microtubules;Mitotic spindle;Modeling;Molecular;molecular dynamics;Motility;Motor;Muscle;Muscle Development;Mutagenesis;mutant;Mutation;Neocortex;Neuroglia;Neuromuscular Diseases;Neurons;Neutrons;NMR Spectroscopy;novel;Nuclear;Nuclear Envelope;Nuclear Pore;Nuclear Pore Complex Proteins;Pathway interactions;Play;Pore Proteins;Positioning Attribute;Process;Proteins;Radial;reconstitution;recruit;Registries;Regulation;Resolution;Roentgen Rays;Role;Running;Signal Transduction;single molecule;Site;Slide;spatiotemporal;Speed;Spinal Muscular Atrophy;stem cells;Structure;Synapses;Testing;Titrations;transmission process;X-Ray Crystallography

PROJECT_TITLE: Regulation of  bidirectional transport of the nucleus by adapter proteins

STUDY_SECTION: MSFC

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


ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

ORG_STATE: CA

PHR: Narrative: Understanding the allosteric communication mechanisms of how agonist binding to G- protein coupled receptors (GPCRs) allow selective coupling to their cognate G-proteins is the holy grail of functional selectivity in GPCRs. The proposed interdisciplinary research will develop computational methods concurrent with experiments to provide insight into the dynamics and structural basis of how class A GPCRs recognize their cognate G-proteins. The combination of computational methods and experiments will provide an understanding of how agonists with varied efficacies affect the functional selectivity and pave way to designing ligands with functional selectivity for GPCRs for treatment of hypertension, diabetes and cancer.

PI_NAMEs: VAIDEHI, NAGARAJAN  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Affect;Agonist;Angiotensin Receptor;Binding;Binding Sites;Biological Assay;Biological Process;Cells;Code;Collaborations;Communication;Complex;Computing Methodologies;Coupled;Coupling;design;Diabetes Mellitus;drug discovery;Drug Targeting;Engineering;Exhibits;experimental study;Explosion;extracellular;Fluorescence Resonance Energy Transfer;Funding;G alpha q Protein;G-Protein Signaling Pathway;G-Protein-Coupled Receptors;Goals;Grant;GTP-Binding Proteins;hypertension treatment;insight;Interdisciplinary Study;Knowledge;Ligand Binding;Ligands;Malignant Neoplasms;Measurement;Measures;Mediating;Methods;Modeling;Molecular Conformation;molecular dynamics;molecular scale;Outcome;Pathway interactions;Pharmaceutical Preparations;Process;protein complex;Protein Dynamics;receptor;Research Proposals;Resolution;Role;sensor;Shapes;side effect;Signal Pathway;Site;spectroscopic survey;structural determinants;Structure;Techniques;Testing;Therapeutic;three dimensional structure;Tissues;tool;Universities;Variant;Work

PROJECT_TITLE: Structural dynamics underlying GPCR-G protein selectivity

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Mental Health;Prevention;Sexually Transmitted Infections;Social Determinants of Health

ORG_CITY: BRONX

ORG_DEPT: PSYCHIATRY

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Stigma remains a pernicious impediment to health, deterring engagement in services that are vital to ending the HIV epidemic. This K23 plans to integrate frameworks from stigma and implementation science to explore drivers and mitigators of sexual stigma in healthcare, and then to develop and pilot an intervention for health workers that mitigates stigma during their interactions with gay and bisexual men. This approach to intervention development optimizes the likelihood of yielding high acceptability, feasibility, and appropriateness among those intended to benefit from the intervention’s use in healthcare settings, and holds the promise of identifying broadly applicable and theory-based behavior change techniques and mechanisms of action to mitigate stigma among health workers in ways that improve the quality of care and HIV-related outcomes among stigmatized groups.

PI_NAMEs: KUTNER, BRYAN A. (contact)

PROGRAM_OFFICER_NAME: GREENWOOD, GREGORY LOUIS

PROJECT_TERMS: Acceleration;AIDS prevention;Algorithms;Anal Sex;Anus;Attitude;Award;Behavior;behavior change;Behavior Therapy;Behavioral;Belief;Bisexual;career;career development;Caring;Collaborations;Communication;Competence;condoms;Counseling;Data;Dedications;design;Development Plans;Disclosure;Discrimination;E-learning;Education;Educational workshop;effectiveness testing;Environment;Epidemic;Equipment and supply inventories;Evaluation;Evidence based program;Expert Opinion;follow-up;Funding;Future;Gays;gender minority group;Goals;Health;health care settings;health communication;Health Personnel;health training;Healthcare;HIV;HIV Infections;HIV/STD;HIV/STI intervention;Human;hybrid type 2 design;implementation framework;implementation intervention;implementation outcomes;implementation science;improved;Incidence;Intention;Intervention;Interview;Knowledge;Learning;Link;Longitudinal Surveys;Lubricants;Malignant Neoplasms;Mediation;men;men who have sex with men;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methods;mHealth;Modeling;novel;Outcome;Pamphlets;Persons;Physiology;Population;prevent;Prevention;Process;Prophylactic treatment;Provider;Quality of Care;Recording of previous events;rectal microbicide;Reporting;Research;Research Personnel;Resources;response;Risk;Risk Factors;Sampling;Scientist;screening;Services;Sex Behavior;sexual minority group;sexual minority health;Sexuality;skills;social stigma;Stigmatization;Techniques;Technology;Testing;Theoretical Domains framework;theories;Theory of Change;therapy development;tool;Training;transmission process;Triage;United States National Institutes of Health;uptake;Viremia;Visit;Visualization;Well in self;Work;Workforce Development

PROJECT_TITLE: Mitigating sexual stigma within healthcare interactions to improve engagement of MSM in HIV prevention


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: This proposal will examine the effects of infection with the SARS-CoV-2 coronavirus (more commonly known as COVID-19) on mental health, cognition, and social integration in recently housed Veterans and Veterans without a history of chronic homelessness. It is evident that the effects of the pandemic on mental health and functioning will be felt for years to come. Many Veterans who have contracted COVID-19 are continuing to exhibit severe cognitive and psychological impacts months after recovering from the acute illness. Furthermore, we do not know the impact of the pandemic on recently housed Veterans, who are considered a vulnerable population. This project will prospectively examine over 18 months cognition, mental health, and social integration in a large sample of vulnerable and non-vulnerable Veterans who have or have not been infected with COVID-19.

PI_NAMEs: WYNN, JONATHAN  (contact)

PROJECT_TERMS: 2019-nCoV;Acute;Address;administrative database;Affect;American;Anxiety;Area;Buffers;Chronic;Cities;Cognition;Cognitive;cognitive function;combat;Community Integration;Contracts;coping;Coronavirus;Coronavirus Infections;Country;COVID-19;COVID-19 impact;COVID-19 pandemic;Cross-Sectional Studies;Data;Databases;Economics;effective therapy;Environment;Exhibits;experience;Face;Family;future pandemic;Home;Homelessness;Housing;improved;Individual;Infection;infection risk;Intervention;Interview;Joints;Knowledge;Long-Term Effects;Los Angeles;Measures;Mental Depression;mental function;Mental Health;metropolitan;Nature;Neurologic;Outcome;pandemic disease;pandemic impact;Participant;Pattern;Persons;Phase;Population;Post-Traumatic Stress Disorders;prospective;protective factors;Psychological Factors;Psychological Impact;psychological outcomes;Recording of previous events;Recovery;recruit;Relaxation;remote assessment;Research Proposals;resilience;Risk Factors;Sampling;SARS-CoV-2 infection;SARS-CoV-2 positive;Series;service utilization;social;Social Distance;social integration;Telephone;Textiles;Time;treatment strategy;Uncertainty;United States;Vaccinated;Vaccination;Veterans;Virus;Virus Diseases;Vulnerable Populations

PROJECT_TITLE: The Enduring Effects of COVID-19 Infection on Psychological Factors, Cognition, and Social Integration inRecently Homeless Veterans

STUDY_SECTION_NAME: Behavioral Health & Social Reintegration[RRD4]


ADMINISTERING_IC: HL

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cystic Fibrosis;Digestive Diseases;Gene Therapy;Genetics;Liver Disease;Lung;Nanotechnology;Rare Diseases

ORG_CITY: CAMBRIDGE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: The proposed research will improve the available tools for editing the human genome, which has the potential to treat or cure a broad variety of devastating genetic disorders. Thus, this proposal will advance the NIH’s core mission to improve human health through new, safe, and effective therapies.

PI_NAMEs: ANDERSON, DANIEL G (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Bar Codes;base editing;Cells;Chimeric Proteins;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;combinatorial chemistry;Combinatorial Chemistry Techniques;Cystic Fibrosis;Dangerousness;design;Development;Disease;disease model;disease-causing mutation;DNA;DNA Double Strand Break;Drug Kinetics;effective therapy;Encapsulated;Endonuclease I;Epithelium;Event;experimental study;follow-up;Formulation;Fumarylacetoacetase;Gene Delivery;gene editing technology;gene-editing approach;Genes;Genetic Diseases;Genome;genome editing;Health;Hereditary Disease;Human;Human Genome;Hydrolase;improved;In Vitro;in vitro testing;in vivo;in vivo evaluation;Inbred CFTR Mice;Individual;Intravenous;Libraries;Lipid Inclusion;lipid nanoparticle;Lipids;Liver;Liver diseases;Lung;Lung Diseases;Measures;Mission;mouse model;Mus;Mutation;nanoformulation;nanoparticle delivery;Nebulizer;novel;novel strategies;Organ;Phenotype;pre-clinical;prime editing;prime editor;Property;Proteins;Reporting;Research;RNA;RNA delivery;RNA-Directed DNA Polymerase;Somatic Cell;Sorting;stem cells;Structure;System;Techniques;Technology;Testing;Time;Tissues;tool;Toxic effect;Tyrosinemias;United States National Institutes of Health;Writing

PROJECT_TITLE: Nonviral delivery techniques for in vivo prime editing

STUDY_SECTION: GDD

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


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biotechnology;Infectious Diseases;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: MADISON

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Lymphatic ﬁlariasis is a mosquito-transmitted nematode (roundworm) parasitic disease that infects millions of people worldwide, causing chronic disability and physical disﬁgurement. The goal of this research is to leverage technical advances we have made to (1) gain a better understanding of a parasite tissue system that is essential to how parasites communicate with and manipulate their hosts, and (2) to identify and proﬁle receptors within this system that can potentially be targeted to disrupt the establishment or maintenance of infection.

PI_NAMEs: ZAMANIAN, MOSTAFA  (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Address;Adult;Anthelmintics;Antiparasitic Agents;Bioinformatics;Biological Assay;Biological Process;Brugia;Brugia malayi;Caenorhabditis elegans;candidate identification;Cell Surface Receptors;cell type;Cells;Chemicals;Chronic disability;Communication;Culicidae;Data;Development;Diagnostic;disorder control;drug discovery;Drug Targeting;Environment;Excretory function;exosome;Filarial Elephantiases;Filariasis;G-Protein-Coupled Receptors;global health;Goals;Health;Helminths;high throughput screening;Human;Immune;immunoregulation;in vitro Assay;Infection;innovation;interest;Ivermectin;Knowledge;Larva;Lead;Life Cycle Stages;Ligands;loss of function;Lymphatic;Maintenance;Mammalian Cell;Measures;Medical;Medicine;Methods;Mining;model organism;Molecular;Nature;Nematoda;Nematode infections;new therapeutic target;novel;novel strategies;Parasite Control;Parasites;Parasitic Diseases;Parasitic nematode;parasitism;pathogen;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacology;Poverty;prevent;Process;programs;Protein Secretion;Proteins;receptor;Receptor Activation;Regulation;Research;Resistance;response;reverse genetics;RNA Interference;Role;screening;Secretory Cell;Source;spatiotemporal;Structure;success;System;Tissue Model;Tissues;transcriptome;transcriptomics;transmission process;Vaccines;Vesicle;Whole Organism

PROJECT_TITLE: Molecular mechanisms controlling secretion in filarial nematode parasites

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: Columbus

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: The successful duplication of a cell's genome involves replication of both the sequence of the DNA and the structure of the genome. Errors in either of these aspects can result in numerous human diseases. The goal of this proposal is to define how dynamic histone acetylation regulates the epigenetic inheritance of genome structure.

PI_NAMEs: PARTHUN, MARK R (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: 3-Dimensional;Acetylation;Architecture;Cell division;Cell Maintenance;Cell Nucleus;Cells;Chromatin;chromatin modification;Chromatin Structure;Complex;Cytoplasm;Data;Daughter;Defect;density;Deposition;DNA;DNA biosynthesis;DNA Modification Process;DNA replication fork;DNA Sequence;Epigenetic Process;epigenome;epigenomics;Eukaryota;experimental study;Gene Expression;Genes;genetic approach;Genetic Transcription;Genome;Genome Stability;Genomic DNA;Goals;HAT1 gene;Heterochromatin;Histone Acetylation;histone acetyltransferase;Histone H3;Histone H4;histone modification;Histones;human disease;infancy;innovation;insight;Knowledge;Laboratories;Lamins;Link;Location;Mammalian Cell;mammalian genome;Methylation;Modeling;Modification;Molecular Genetics;non-histone protein;Nuclear;Nuclear Lamina;Nucleosomes;Outcome;Pathway interactions;Pattern;Phenocopy;Play;Post-Translational Protein Processing;preservation;programs;Proteins;Recycling;Regulation;Research;restoration;Role;S phase;Solid;spatial memory;Structure;Therapeutic;three dimensional structure;Work

PROJECT_TITLE: Histone Acetylation Dynamics and Epigenome Duplication

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Precision Medicine;Women's Health Research

PHR: Project Narrative Our team recently led the clinical development of Sacituzumab Govitecan (SG, aka Trodelvy), the first FDA- approved antibody-drug conjugate (ADC) for triple-negative breast cancer (TNBC), leading to substantially improved outcomes for this most aggressive and poor-prognosis breast cancer subtype. Here, we propose to build on this success by testing a new targeted drug combination incorporating SG for resistant tumors, and by developing biomarkers and additional combinations to guide rational use of this new treatment approach. We seek to move potentially transformative new combination therapies rapidly into clinical trials.

PI_NAMEs: BARDIA, ADITYA ;ELLISEN, LEIF W (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Acceleration;Antibody-drug conjugates;Basic Science;Biological Markers;Biopsy;Breast Cancer Cell;Breast Cancer Patient;cancer subtypes;Cell model;Cells;chemotherapy;Clinical;clinical biomarkers;clinical development;Clinical Sciences;clinical trial analysis;Clinical Trials;clinically relevant;combinatorial;Combined Modality Therapy;Complement;Complex;Coupled;CRISPR screen;Data;Disease;DNA Damage;DNA Repair;Dose;Drug Combinations;Drug Targeting;druggable target;Exhibits;exome sequencing;experience;FDA approved;Funding;homologous recombination;humanized monoclonal antibodies;Immunohistochemistry;improved;improved outcome;in vivo;in vivo evaluation;inhibitor;innovation;irinotecan;Lead;Link;Malignant Breast Neoplasm;Mediating;Modeling;Molecular Analysis;Morbidity - disease rate;mortality;new combination therapies;new therapeutic target;next generation;novel;novel therapeutic intervention;objective response rate;optimal treatments;Organoids;PARP inhibition;Pathway interactions;patient derived xenograft model;patient subsets;Patients;Pharmaceutical Preparations;pharmacodynamic biomarker;Phase;Phase Ib/II Clinical Trial;PIK3CG gene;Preclinical Testing;predicting response;Prediction of Response to Therapy;Prognosis;Progression-Free Survivals;Refractory;repaired;Research Personnel;Resistance;resistance mechanism;response;Sampling;Schedule;Series;SN-38;success;synergism;Testing;Therapeutic;Therapeutic Trials;Therapeutic Uses;Topoisomerase;Toxic effect;transcriptome sequencing;translational goal;Translational Research;treatment response;Treatment-related toxicity;triple-negative invasive breast carcinoma;Triplet Multiple Birth;tumor;Tumor Antigens;Validation;Work

PROJECT_TITLE: Synergistic combinatorial DNA damage response/repair inhibition and Sacituzumab Govitecan in triple-negative breast cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Clinical Research;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Anaphylaxis is a potentially life-threatening IgE-mediated systemic allergic reaction with no known preventative therapies. Our preliminary data suggest that pharmacologic inhibitors of Bruton’s tyrosine kinase (BTK) can prevent IgE-mediated human mast cell and basophil activation in vitro and in humanized mouse models in vivo. Specific aims will determine the ability of BTK inhibitors to prevent drug-induced anaphylaxis, in addition to further defining the kinetics and degree of their efficacy as potential therapies for preventing anaphylaxis in humans.

PI_NAMEs: DISPENZA, MELANIE C. (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Accidents;Agammaglobulinaemia tyrosine kinase;Allergen Immunotherapy;Allergens;Allergic;Allergic Reaction;Anaphylaxis;Award;B-Cell Antigen Receptor;B-Lymphocytes;Basophils;beta-n-acetylhexosaminidase;Biological Markers;Biometry;Board Certification;career;CCL2 gene;CD34 gene;cell type;Cells;Cellular biology;Clinical;clinical care;Clinical Immunology;Clinical Trials;cost;cost effective;Cutaneous;cytokine;Data;desensitization;design;Development;Doctor of Philosophy;Dose;efficacy evaluation;Engraftment;Epinephrine;experimental study;Exposure to;FDA approved;Food;food challenge;Frequencies;Funding;Goals;Grant;Histamine;Human;human model;human tissue;humanized mouse;Hypersensitivity;Hypersensitivity skin testing;IgE;IL8 gene;Immune response;Immunologist;Immunology;Immunotherapy;improved;In Vitro;in vivo;in vivo Model;Inflammatory;inhibitor;Inpatients;Insect Sting;Interleukin-6;Kinetics;Learning;Leukocytes;Leukotriene C4;Life;Logic;mast cell;Measurement;Mediating;Mediator;medical schools;Medicine;Mentors;mouse model;Mus;novel;novel strategies;novel therapeutics;Nuts;open label;Oral;particle;Pathway interactions;Patient Care;patient oriented;Patient-Focused Outcomes;Patients;Penicillin Allergy;Penicillins;Peripheral;Pharmaceutical Preparations;pharmacologic;Phase;Phenotype;Phosphotransferases;Plasma;prevent;Preventive therapy;Principal Investigator;Production;professor;Prostaglandin D2;Qualifying;Reaction;Receptor Signaling;Research;Research Design;Research Personnel;Risk;risk mitigation;Role;Sampling;Scientist;Serum;Severities;Signal Pathway;Signal Transduction;skills;Skin;skin prick test;Small Interfering RNA;Specificity;standard of care;stem cells;Stimulus;Study Skills;Testing;Tissues;TNF gene;Training;translational physician;Translational Research;Trees;Tryptase;Tyrosine Kinase Inhibitor;Universities;Venoms;Work;X-Linked Agammaglobulinemia

PROJECT_TITLE: Using BTK Inhibitors to Prevent Anaphylactic Drug Reactions

STUDY_SECTION: AITC

STUDY_SECTION_NAME: Allergy, Immunology, and Transplantation Research Committee[AITC]


NIH_SPENDING_CATS: Nutrition

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE   Given the involvement of ERK signaling in several diseases including Alzheimer disease, diabetes, obesity and  cancer,  this  proposal  will  establish  a  new  level  of  understanding  of  how  ERK  directly  regulates  activity  of  the  metabolic  pathways  essential  for  cellular  homeostasis.  Our  preliminary  data  place  us  in  the  unique  position  to  uncover and understand at a biochemical and molecular level new regulatory processes, new biomarkers and  new potential strategies that are needed for personalized therapeutic intervention in metabolic diseases that can  be driven by improper ERK signaling.

PI_NAMEs: BEN-SAHRA, ISSAM  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Acute;Adipocytes;Alzheimer's Disease;base;Biochemical;Biogenesis;Biological Assay;Biological Markers;Biology;Biomass;Bone Marrow;c-myc Genes;Cancer cell line;Catabolic Process;CD3 Antigens;CD8B1 gene;Cell Cycle Progression;Cell Differentiation process;cell growth;Cell membrane;Cell Physiology;Cell Proliferation;Cells;Cellular Metabolic Process;Chemicals;Complex;cytokine;Data;Diabetes Mellitus;Disease;DNA biosynthesis;Environment;Enzymes;Epithelium;Event;fighting;FRAP1 gene;Genetic Transcription;Glutamine;Goals;Growth;Growth Factor;Guanosine Triphosphate;Hela Cells;Homeostasis;Human Cell Line;human disease;In Vitro;inhibitor;insight;interest;isotope incorporation;Isotopes;Knock-out;liquid chromatography mass spectrometry;macromolecule;Malignant Neoplasms;Mammalian Cell;MAP Kinase Gene;Measures;Mediating;MEK inhibition;MEKs;Metabolic;Metabolic Control;Metabolic Diseases;Metabolic Pathway;Metabolism;metabolomics;Mitogens;Molecular;mutant;Nerve Degeneration;Non-Insulin-Dependent Diabetes Mellitus;Normal Cell;novel therapeutic intervention;Nucleic Acids;nucleotide metabolism;Nucleotides;Nutrient;Obesity;Oncogenic;Organism;Pathologic;Pathology;Pathway interactions;personalized therapeutic;phosphoproteomics;Phosphorylation;Phosphotransferases;Physiological;PIK3CG gene;Play;Positioning Attribute;Post-Translational Protein Processing;Process;Production;Proliferating;Protein-Serine-Threonine Kinases;Proteins;Proteomics;purine metabolism;Purines;Pyrimidine;Pyrimidines;raf Kinases;Ras/Raf;reconstitution;Recurrence;Recycling;Regulation;resistance mechanism;response;Ribosomes;RNA chemical synthesis;Role;Science;Serine;Signal Pathway;Signal Transduction;Spleen;System;T-Lymphocyte;Therapeutic Intervention;therapeutic target;Tissues;Tracer;transcription factor;Western Blotting

PROJECT_TITLE: Regulation of de novo purine synthesis by the MAPK/ERK pathway

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PUBLIC HEALTH STATEMENT High blood pressure is an enormous health care burden in the United States, affecting one in three adults. It is a major cause of stroke, heart attack and kidney disease and despite this, the causes of hypertension remain poorly understood and treatment is not always successful. In our proposed studies, we will further define the inflammation that causes hypertension and develop new strategies to prevent this.

PI_NAMEs: HARRISON, DAVID G (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: adaptive immunity;adduct;Adult;Affect;Antigen-Presenting Cells;Biological Markers;CD8-Positive T-Lymphocytes;Cells;Collaborations;Data;Dendritic Cells;Disease;Experimental Models;healthcare burden;Histocompatibility Antigens Class I;Human;Hypertension;hypertensive;IL17 gene;immune activation;Immunization;immunogenic;Individual;Inflammation;Interferon Type II;Kidney Diseases;Lipids;Major Histocompatibility Complex;Mass Spectrum Analysis;Mitochondria;monocyte;Mus;Myocardial Infarction;NADPH Oxidase;Natural Immunity;neoantigens;novel;oxidation;Pathogenicity;Peptides;prevent;Process;programs;Proliferating;Proteins;Public Health;Reactive Oxygen Species;Research;Severity of illness;single cell sequencing;Source;Stroke;T memory cell;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;translational immunology;United States

PROJECT_TITLE: Mechanisms of Immune Activation in Hypertension


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biotechnology;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: IRVINE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative The proposed studies will provide some of the first insights into mechanisms for how the force of muscle contraction influences gene expression and extracellular matrix assembly during tendon development. Understanding how muscle attachments develop will enhance our ability to discover pharmacological treatments for tendon injuries and atrophy with aging. It will also inform strategies for producing stem/progenitor cells to repair damaged tendons and ligaments as well as genetic disorders of human tendons.

PI_NAMEs: SCHILLING, THOMAS F (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: absorption;Address;Aging;Atrophic;Binding Proteins;bone;cell type;Cells;Cephalic;Contracts;craniofacial;Data;Development;developmental genetics;Disease;effective therapy;Embryo;experimental study;Extracellular Matrix;Feedback;Fibroblasts;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Genetic;Genetic Diseases;genetic manipulation;Genetic study;Genetic Transcription;Goals;Head;Heterogeneity;Human;Image;In Situ;in vivo;in vivo imaging;insight;Knowledge;ligament injury;Ligaments;Limb structure;Location;Maintenance;mechanical force;mechanical load;Mesoderm;Methods;Molecular;Morphogenesis;Mus;Muscle;Muscle Contraction;Musculoskeletal Development;Musculoskeletal System;mutant;Neural Crest Cell;novel;Paralysed;pharmacologic;Pharmacological Treatment;Physiological;Play;Population;Production;progenitor;Property;Regulation;repaired;Research;response;Role;scaffold;Scaffolding Protein;scleraxis;Shock;Signal Transduction;single-cell RNA sequencing;Site;skeletal;Sorting;Specific qualifier value;stem cells;tendon development;Tendon Injuries;Tendon structure;Testing;thrombospondin 4;Thrombospondins;Tissues;transcription factor;transcriptomics;Transforming Growth Factor beta;Tretinoin;Variant;Weight-Bearing state;Zebrafish

PROJECT_TITLE: Developmental regulation of cranial tendon fibroblast diversity and ECM interactions

STUDY_SECTION: SBDD

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


NIH_SPENDING_CATS: Cancer;Genetics;Radiation Oncology

ORG_CITY: HERSHEY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: Project Narrative Replication fork stability is essential for suppressing genome mutagenesis. This application will investigate novel roles for PARP14 proteins in genomic stability. PARP14 may represent a novel biomarker to predict the risk of cancer development and the tumor response to cancer therapy.

PI_NAMEs: MOLDOVAN, GEORGE LUCIAN (contact)

PROJECT_TERMS: ADP ribosylation;Affect;Binding;Biochemical;Biological Assay;BRCA deficient;BRCA1 gene;BRCA2 Protein;cancer risk;cancer therapy;carcinogenesis;Cell Physiology;cell type;Cells;chemotherapy;Chemotherapy and/or radiation;Chromosomal translocation;Clinic;Clinical;Complex;Development;DNA;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA lesion;DNA Repair;DNA replication fork;Double Strand Break Repair;environmental agent;Excision;EXO1 gene;Family;Genome;Genome Stability;Genomic DNA;Genomic Instability;genotoxicity;Germ Lines;Goals;Health;homologous recombination;Human;inhibitor;Knowledge;Lesion;Measures;Mediating;member;Mutagenesis;mutant;novel;novel marker;nuclease;Pathway interactions;Process;Proteins;Radiation;radiation resistance;radiation response;Radiation Tolerance;recruit;Resistance;response;risk prediction;Role;Single-Stranded DNA;Sister Chromatid;Site;Structure;Testing;translocase;tumor;Tumor Markers;Tumor Suppression

PROJECT_TITLE: The Role of Mono-ADP-Ribosylation by PARP14 in Radioresistance

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ORG_CITY: SANTA BARBARA

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: Project Narrative: Novel and highly efficient synthetic methods developed in this proposal could be applied in and/or facilitate the preparation of bioactive compounds either as small molecular probes for elucidating medically relevant biological pathways or as drug candidates for disease management.

PI_NAMEs: ZHANG, LIMING  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Development of Asymmetric Cooperative Gold Catalysis and Beyond

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


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Clinical Research;Pediatric;Social Determinants of Health

ORG_CITY: New York

ORG_NAME: TEACHLEY, LLC

PHR: Project Narrative  There is an enormous need for students majoring in the fields of Science, Technology, Engineering and Mathematics (STEM), yet lacking a strong foundation in mathematics makes students, especially women, minorities and those from low-income backgrounds, less likely to pursue careers in STEM. Teachley Problem Solving will bolster students’ mathematics abilities, including mathematical reasoning, problem-solving and self-efficacy in the short and long term. This will, in turn, lead to several positive distal outcomes, such as increased STEM majors and careers.

PI_NAMEs: CARPENTER, KARA  (contact)

PROGRAM_OFFICER_NAME: FAUPEL-BADGER, JESSICA

PROJECT_TERMS: Belief;career;Child;Classification;Computer software;dashboard;Data;data integration;data tools;design;digital;digital tool;Distal;education resources;Educational Curriculum;elementary school;Ensure;Environment;Feedback;fifth grade;formative assessment;Foundational Skills;Foundations;Geometry;Goals;Grant;Health;high school;High School Student;improved;Ingestion;Instruction;intervention effect;Investments;Learning;Low income;lower income families;Marketing;mathematical ability;mathematical learning;mathematical model;mathematical theory;Mathematics;Mathematics Curriculum;Minority;Modeling;Outcome;Performance;Persons;Phase;Problem Sets;Problem Solving;prototype;Qualifying;Research;Sales;Science, Technology, Engineering and Mathematics;Self Efficacy;skills;STEM career;STEM field;Structure;student participation;Students;success;teacher;Testing;Time;tool;Underrepresented Minority;usability;Visual;Woman

PROJECT_TITLE: Building a mathematical problem-solving environment to prepare K-5 students for success in STEM and health careers.


NIH_SPENDING_CATS: Autoimmune Disease;Genetics;Kidney Disease;Rare Diseases

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative The immune system maintains a careful balance between protecting the body from infectious pathogens and the collateral damage that may arise as a result of too much inflammation, particularly autoimmunity. Interleukin (IL)-17 is an important mediator of immune inflammation and protects against various microorganisms. However, an overabundance of IL-17 signaling contributes to the pathogenesis of autoimmunity. Autoimmune kidney damage (glomerulonephritis) is serious consequence of many autoimmune conditions that impact the kidney, and emerging data implicate IL-17 in driving this process. Although we know quite a bit about which cells make IL-17, the molecular process of IL-17 cellular activation in the kidney is poorly defined. This proposal focuses on understanding how regulation of IL-17-driven gene expression promotes pathology in autoimmune kidney disease.

PI_NAMEs: GAFFEN, SARAH L (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: ANCA vasculitis;Antibodies;Antigen Targeting;Antineutrophil Cytoplasmic Antibodies;Autoantibodies;Autoimmune;Autoimmune Diseases;Autoimmunity;autoinflammation;autoinflammatory;Automobile Driving;Binding;Biological;Biological Markers;Biological Response Modifiers;Biopsy;Blood Vessels;CCAAT-enhancer-binding protein-delta;CCAAT-Enhancer-Binding Proteins;cell type;Cells;chemokine;Complex;cytokine;Cytokine Signaling;Data;Deposition;Disease;Drug Targeting;Elements;Epithelial Cells;Equilibrium;Event;Gene Expression;Generations;Genes;Glomerulonephritis;Goals;Goodpasture Syndrome;Half-Life;Helper-Inducer T-Lymphocyte;Human;IL17 gene;Image;Immune system;Immunology;Impairment;improved;in vivo;Inflammation;Interleukin-6;Kidney;kidney biopsy;kidney cell;Kidney Diseases;LCN2 gene;Mediating;Messenger RNA;microorganism;Modification;Molecular;Molecular Target;mouse model;murine antibody;Mus;Neutrophil Infiltration;novel;Organ;pathogen;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;Physiological;Post-Transcriptional Regulation;posttranscriptional;Process;Publishing;Regulation;renal damage;Resistance;RNA;RNA-Binding Proteins;Role;Signal Transduction;success;targeted treatment;Tissues;transcription factor;Translations;Tubular formation;Up-Regulation

PROJECT_TITLE: RNA binding proteins in end-organ autoimmune pathology

STUDY_SECTION: HAI

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


ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Narrative A key feature of the immune system is the generation of “memory”, which allows us to become “immune” after the first encounter with a pathogen or vaccine, successfully fending off future encounters with that pathogen. One population of memory cells, called memory T cells, come in a variety of “flavors” which exhibit distinct functional properties – one major subdivision is into memory T cells that patrol the body incessantly (recirculating memory cells) and ones that stay in tissues long-term (resident memory cells) , which can promptly respond to local infections. Key to immune “memory” is that these T cell populations last long-term (decades in humans, years in mice) and preserve their distinct “identities” (e.g. as recirculating or resident cells): however, while this has been a topic of considerable interest for decades, discrepancies in published studies need to be resolved in order to determine how memory T cells are maintained. We will use sophisticated genetic models, as well as pharmaceutical treatments, to accurately determine how distinct subsets of memory T cells are sustained by the soluble factors (called cytokines) IL-7 and IL-15 and how the “identity” of recirculating and resident memory cells is maintained by expression of a DNA binding protein called KLF2 and some of the genes it regulates. These studies will give us an improved understanding of how memory T cell maintenance is maintained and identify areas of potential therapeutic intervention to enhance or reshape the T cell memory population for clinical goals.

PI_NAMEs: JAMESON, STEPHEN C (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: Address;Affect;Area;Biological Models;Blood;cancer immunotherapy;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Maintenance;Cells;Characteristics;Circulation;Clinical;Cues;cytokine;Data;differential expression;DNA-Binding Proteins;Environment;Equilibrium;Exhibits;Focal Infection;Future;Gene Knock-Out Model;Generations;Genes;genetic manipulation;Genetic Models;Goals;Homeostasis;Host Defense;Human;IL7 gene;Immune;Immune system;Immunity;Immunologic Memory;immunopathology;improved;Infection;interest;Interleukin-15;Investigation;knockout gene;Knowledge;Literature;Maintenance;Memory;Modeling;mouse genetics;Mus;Names;novel;pathogen;Pathogenicity;Pathway interactions;Pattern;Pharmaceutical Preparations;Pharmacologic Substance;Pharmacological Treatment;Play;Population;preservation;prevent;Procedures;programs;Proliferating;Property;Publishing;Residencies;response;restraint;Role;Route;Shapes;Signal Transduction;Sphingosine-1-Phosphate Receptor;System;T cell response;T memory cell;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic;Therapeutic Intervention;Tissues;trafficking;transcription factor;Vaccines;Work

PROJECT_TITLE: T Cell Homeostasis


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: SALT LAKE CITY

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: NARRATIVE The current next generation sequencing (NGS) data analysis turnaround, not sequencing itself, is too slow for time sensitive clinical applications, such as identifying the optimal treatment for a cancer patient days after biopsying, and according to the unique genomic characteristics of that patient’s tumor. This exploratory development proposal aims to greatly accelerate genomic analysis (60X whole human genome in 10 minutes) using heterogeneous computing techniques. In addition to enabling NGS for time critical clinical applications, our emphasis on an open-source development model, reusable software components, and the acceleration of widely used algorithms will allow for the adoption of accelerated computing by a large developer and user community.

PI_NAMEs: MARTH, GABOR T;QIAO, YI  (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Acceleration;Adopted;Adoption;Advanced Malignant Neoplasm;Algorithmic Analysis;Algorithms;analysis pipeline;Area;Artificial Intelligence;base;Bioinformatics;Biopsy;Cancer Patient;cancer therapy;Characteristics;Childhood;Clinic;Clinical;clinical application;clinically relevant;Code;Collaborations;Collection;Communities;Computer software;computerized data processing;Consumption;cost;Critically ill children;Data;Data Analyses;Data Set;Democracy;design;Development;Diagnostic;DNA sequencing;Drops;Exclusion;experience;Funding Opportunities;Future;Generations;Genome;genome sequencing;genome-wide;Genomics;Germ-Line Mutation;gigabyte;Goals;Hour;Human Genome;Informatics;informatics tool;Laboratories;Libraries;Manuals;Mathematics;Measures;Modality;model development;Mutation Detection;Neonatal Intensive Care Units;next generation sequencing;open source;optimal treatments;parallelization;Patients;Performance;Positioning Attribute;precision medicine;precision oncology;Process;programs;Research;Selection for Treatments;Sequence Alignment;Somatic Mutation;Speed;success;task analysis;Techniques;Time;tool;tumor;Variant;whole genome;Work

PROJECT_TITLE: Accelerating genomic analysis for time critical clinical applications

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA MEDICAL RESEARCH FOUNDATION

ORG_STATE: OK

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because the discovery of mechanisms through which proteases negatively impact vascular integrity could be therapeutically beneficial for combating pathologies associated with dangerous or debilitating hemorrhage or edema. Thus, the proposed research supports the NIH mission of developing knowledge that will help reduce illness and lengthen life.

PI_NAMEs: GRIFFIN, COURTNEY T (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: angiogenesis;Area;Award;blood damage;Blood Vessels;Cell Death;Dangerousness;Data;Development;Disease;Edema;Embryonic Development;Endothelial Cells;Endothelium;Extracellular Matrix Degradation;genetic approach;Genetic Models;Health;Hemorrhage;in vivo;Inflammation;Knowledge;Life;lymphatic vessel;Mediating;Mission;Mus;National Heart, Lung, and Blood Institute;new therapeutic target;Pathology;Peptide Hydrolases;Phenotype;postnatal;Prevention;Proteolysis;Public Health;Publishing;Research;Research Personnel;Research Support;Role;Rupture;scaffold;Signal Transduction;Site;Therapeutic;Thrombosis;Tissues;United States National Institutes of Health;Vascular Diseases;Work

PROJECT_TITLE: Protease-Mediated Vascular Instability in Development and Disease


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Chronic Pain;Disability Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Opioid Misuse and Addiction;Opioids;Pain Research;Physical Injury - Accidents and Adverse Effects;Prevention;Rehabilitation;Social Determinants of Health;Substance Misuse

ORG_CITY: NEW YORK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: People with physical disabilities may be particularly vulnerable to opioid misuse and overdose, as they have a high prevalence of chronic pain due to musculoskeletal conditions and high exposure to opioid analgesics. However, disabled adults have been largely left out of research into the prevention and treatment of opioid use disorder and overdose. This project will improve understanding of the mechanisms that place low-income, disabled adults at increased risk of opioid overdose, as well as the potential for improved pain management practices and increased receipt of recommended treatments for substance use disorder and chronic pain to reduce overdose risk in this population.

PI_NAMEs: RUDOLPH, KARA ELIZABETH (contact)

PROGRAM_OFFICER_NAME: SU, SHELLEY

PROJECT_TERMS: Adult;Affect;Affordable Care Act;Aftercare;attributable risk;beneficiary;Benzodiazepines;Cessation of life;Chronic;chronic pain;chronic pain management;chronic painful condition;comorbidity;Confounding Factors (Epidemiology);County;Deaths of despair;Disabilities experience;disability;disabled;Disabled Persons;Disease Management;Disparity;Economics;Eligibility Determination;Ethnic Origin;Ethnic Population;Exclusion;Exposure to;Future;Gender;geographic difference;Geography;Goals;High Prevalence;high risk;Hospitalization;improved;indexing;Individuals with physical disabilities;Injury;Insurance;Intervention;Joints;Left;Link;Literature;Low income;Machine Learning;Mediating;Mediation;Mediator;Medicaid;Mental Depression;Methods;middle age;multimodality;Musculoskeletal;National Institute of Drug Abuse;non-cancer pain;novel;Opioid;Opioid Analgesics;opioid epidemic;opioid misuse;opioid overdose;opioid use disorder;Outcome;Overdose;overdose death;Overdose reduction;overdose risk;Pain;Pain management;Pathway interactions;Pharmaceutical Preparations;physically handicapped;Population;Practice Management;prescription opioid;Prevalence;Prevention;Prevention strategy;Probability;Property;Qualifying;Race;Recommendation;Research;Risk;risk mitigation;Risk Reduction;Role;Statistical Methods;Stimulant;stressor;Subgroup;substance use;Substance Use Disorder;substance use treatment;surveillance study;Vulnerable Populations

PROJECT_TITLE: Role of disability and pain in opioid overdose: mechanism and risk mitigation

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Sexually Transmitted Infections;Vaccine Related;Women's Health Research

ORG_CITY: CORVALLIS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: OREGON STATE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The goal of this proposal is to develop a protective gonorrhea vaccine using highly conserved, surface-exposed lipoprotein antigens, displayed in their native conformation on a virus-like particle delivery system, and to define the vaccine-induced mechanism(s) of protection by characterizing the immune response in pre-clinical studies.

PI_NAMEs: SIKORA, ALEKSANDRA ELZBIETA (contact)

PROGRAM_OFFICER_NAME: CONNOLLY, KRISTIE LEE

PROJECT_TERMS: Address;Adjuvant;aluminum sulfate;Antibiotic Resistance;Antibodies;Antibody Response;Antigen Targeting;antigen-specific T cells;Antigens;antimicrobial;B-Lymphocytes;bactericide;Binding;Bioinformatics;Blocking Antibodies;Capsid Proteins;Categories;Cells;Clinical;clinical development;Clinical Trials;cohort;comparative;Complement;Complex;Control Groups;cost effective;Country;Coupling;COVID-19 prevention;Data;density;design;Disease;efficacy evaluation;efficacy study;Ensure;ethnic minority;FDA approved;Female;Fimbriae Proteins;Formulation;Funding;Future;gender minority;Geography;Goals;Gonorrhea;gonorrhea vaccine;Gram-Negative Bacteria;Health;Helper-Inducer T-Lymphocyte;his6 tag;Human;Human Papilloma Virus Vaccine;Human Papillomavirus;Immune;Immune response;Immune system;Immunization;Immunize;immunogenicity;Immunoglobulin A;Immunoglobulin G;Immunoglobulins;Immunology;In Vitro;Incidence;Infection;innovation;Knock-out;Lead;Length;Lipoproteins;Lymphoid Tissue;male;Measures;Memory;Metabolic Clearance Rate;Mining;Molecular Conformation;Morbidity - disease rate;mouse model;Mucous Membrane;Multi-Drug Resistance;Mus;Neisseria gonorrhoeae;neonatal health;neutrophil;novel vaccines;Outcome;Particulate;Pathogenesis;Physiology;Plasma;preclinical efficacy;preclinical study;priority pathogen;protein folding;Protein Subunits;Proteins;Proteomics;Psychological Impact;Public Health;racial minority;receptor binding;Recombinants;Reproductive Health;Research;research and development;Resistance;Resources;response;SARS-CoV-2 spike protein;self assembly;Serum;sexual minority;Sexually Transmitted Diseases;Standardization;statistics;Structure of germinal center of lymph node;Subunit Vaccines;Superbug;Surface;System;T cell response;vaccine candidate;vaccine development;vaccine evaluation;vaccine immunogenicity;vaccine platform;Vaccines;vaccinology;Vagina;vaginal mucosa;Viral Antigens;Virus-like particle

PROJECT_TITLE: Proteomics-Driven Reverse Vaccinology for Gonorrhea

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


NIH_SPENDING_CATS: Natural Products

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE The natural products and pharmacologically relevant compounds stemming from this project have significant biomedical ramifications, specifically in pain, psoriasis, allergy, asthma, emphysema, chronic bronchitis, sleep, antifungal, antimicrobial, and Alzheimer’s disease.

PI_NAMEs: KWON, OHYUN  (contact)

PROJECT_TERMS: Air;Alcohols;Alkaloids;Alkenes;Alkylation;Alzheimer's Disease;Amination;anti-fungal agents;antimicrobial;Area;Ascorbic Acid;Asthma;Breathing;Carbon;carbonyl compound;chemical synthesis;Chemicals;Chemistry;Chronic Bronchitis;Complex;controlled release;Coupling;Disease;functional group;Goals;halogenation;Hydrogen;Hydrogen Bonding;Hydrogen Peroxide;Hydroxylation;Hypersensitivity;Imines;Lactams;macromolecule;Maleic Anhydride;Mediating;Methods;Methylation;Modification;Molecular;Natural Products;novel strategies;Operative Surgical Procedures;Organic Synthesis;oxidation;Oxidation-Reduction;Ozone;Pain;Pathway interactions;Periodicity;pharmacologic;Pharmacologic Substance;Phenols;Physical condensation;pi bond;Preparation;Process;Production;programs;Psoriasis;Pulmonary Emphysema;Reaction;Research;Route;Salts;Side;single bond;Sleep;small molecule;Sodium Chloride;Source;stem;Steroids;Synthesis Chemistry;Technology;Terpenes;tertiary amine;Therapeutic;Transition Elements;Vision

PROJECT_TITLE: Deconstructive Molecular Editing Technology Involving C-C Bond Scission

STUDY_SECTION: SBCA

STUDY_SECTION_NAME: Synthetic and Biological Chemistry A Study Section[SBCA]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Wound Healing and Care

ORG_CITY: BATON ROUGE

ORG_NAME: LOUISIANA STATE UNIV A&M COL BATON ROUGE

ORG_STATE: LA

PHR: PROJECT NARRATIVE Pseudomonas aeruginosa, one of the most problematic antibiotic-resistant Gram-negative pathogens, has a proclivity to form biofilms that are intrinsically tolerant to antibiotics, which is an important reason for the persistence of chronic (biofilm) infections. Our team has discovered proof-of-concept inhibitors of the BfrB-Bfd protein-protein complex which dysregulate bacterial iron metabolism and kill P. aeruginosa in biofilms. This project will improve the proof-of-concept molecules into lead molecules for inhibiting the BfrB-Bfd complex in Gram-negative bacteria.

PI_NAMEs: RIVERA, MARIO  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Acinetobacter baumannii;Address;Affect;Affinity;analog;Animal Model;Anti-Bacterial Agents;Anti-Infective Agents;Antibiotic Resistance;Antibiotic susceptibility;Antibiotic Therapy;antibiotic tolerance;Antibiotics;antimicrobial;Bacteria;bactericide;Binding;Binding Sites;Biology;Cell Death;Cell Survival;Cells;Chemicals;Chronic;chronic wound;Clinical;combat;Complex;Cytosol;cytotoxicity;deprivation;design;diabetic patient;drug development;drug discovery;Drug Industry;Effectiveness;Elderly;Electron Transport;Environment;Escherichia;experience;Generations;Genes;Gram-Negative Bacteria;Health care facility;Healthcare;Homeostasis;Immune response;Impairment;improved;in vivo;in vivo Model;Infection;inhibitor;insight;Invaded;Ions;Iron;iron metabolism;Laser Scanning Confocal Microscopy;Lead;Long-Term Care;Maintenance;Mammalian Cell;medical schools;Metabolism;Microbial Biofilms;Microbial Genetics;Modification;Multi-Drug Resistance;Mus;Mutation;next generation;novel;Organic Synthesis;pathogen;Patient Admission;Pharmaceutical Chemistry;Pharmaceutical Preparations;Phenotype;Physiological;Predisposition;protein complex;protein protein interaction;Proteins;Pseudomonas aeruginosa;rational design;Reaction;research and development;Resistance;Resistance development;resistant strain;small molecule;small molecule inhibitor;Staphylococcus aureus;structural biology;Structure;synergism;Synthesis Chemistry;Testing;Theft;tool;tool development;Work;wound care;Wound Infection;Wound models;X-Ray Crystallography

PROJECT_TITLE: Small molecules for perturbing iron homeostasis in bacterial biofilms

STUDY_SECTION: MSFA

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


NIH_SPENDING_CATS: Asthma;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Lung;Pediatric;Prevention

ORG_CITY: HOUSTON

ORG_DEPT: PEDIATRICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative Ascariasis (roundworm) is the most common intestinal parasitic infection globally and causes severe life-long illness in children. The larval stage ascariasis can cause an asthma-like allergic airway disease. This proposal will identify the immunologic mechanisms of Ascaris-induced allergic airway disease in order to develop interventions that are urgently needed to prevent significant illness in children globally.

PI_NAMEs: WEATHERHEAD, JILL ELIZABETH (contact)

PROJECT_TERMS: Acceleration;Accounting;adaptive immune response;Adaptive Immune System;Advisory Committees;airway hyperresponsiveness;Allergens;allergic airway disease;Antigens;Area;Ascariasis;Ascaris;Asthma;asthma model;Attenuated;authority;Basic Science;career;career development;Cell Physiology;Cells;Child;Child Health;Childhood;college;Communicable Diseases;Communication;Complex;Comprehension;cytokine;Data;Development;Development Plans;Dissection;egg;Environment;Extrinsic asthma;Fibrinogen;fungus;Goals;health disparity;helminth infection;Helper-Inducer T-Lymphocyte;high risk;Hospitalization;Host-Parasite Relations;IgE;Immune;immune activation;Immune response;Immune Tolerance;Immunologics;improved;Infection;Inflammatory;Ingestion;Innate Immune Response;Innate Immune System;innovation;insight;Instruction;Interleukin-13;Interleukin-4;Interleukin-5;Intervention;Intestines;Investments;K-Series Research Career Programs;Laboratories;Larva;Leadership;Ligands;Link;Lung;Mediating;Medicine;meetings;Mentors;Mentorship;microbial;microbial host;migration;Molecular;Molecular Immunology;Morbidity - disease rate;mouse model;Mus;Nematoda;new therapeutic target;novel;Parasitic infection;Parasitology;pathogen;Pathogenesis;Pathway interactions;Peptide Hydrolases;Peripheral;Persons;Phenotype;Physicians;Poverty;prevent;professor;Regulatory T-Lymphocyte;Research;Research Personnel;Research Proposals;Resolution;Resources;response;Role;Schedule;Scientist;Signal Transduction;skills;STAT6 Transcription Factor;Symptoms;Teacher Professional Development;Th2 Cells;Therapeutic;TLR4 gene;Training Activity;Translational Research;translational research program;Tropical Medicine;United States National Institutes of Health;vaccine development;Vaccines

PROJECT_TITLE: Discovering the Immunologic Mechanism of Ascaris-induced Allergic Airway Disease.


NIH_SPENDING_CATS: Biotechnology;Genetics;Infectious Diseases;Sexually Transmitted Infections

ORG_CITY: IOWA CITY

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Project Narrative/Relevance Virus proteins accomplish virus assembly by making critical interactions with each other. Identifying and characterizing those interactions represents a promising avenue for development of viral therapies and vaccines. This proposal presents a new approach to identifying and characterizing these critical interactions.

PI_NAMEs: ROLLER, RICHARD J (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Biological Assay;Capsid Proteins;Cell Culture Techniques;Cells;Complex;Conserved Sequence;Cytoplasm;Data;Defect;Development;Directed Molecular Evolution;Gene Targeting;Genes;Growth;Herpesviridae;Herpesvirus 1;Herpesvirus Type 3;Homologous Gene;Homologous Protein;Human;Immediate-Early Proteins;Maps;mutant;Mutation;novel;novel strategies;Nuclear;Nuclear Envelope;Play;Process;protein complex;Protein Kinase;Protein-Serine-Threonine Kinases;Proteins;Proteomics;Reporting;Role;Simplexvirus;System;Testing;Vaccines;Viral;Viral Genes;Viral Genome;Viral Proteins;Virus;Virus Assembly;Virus Replication;VP 16

PROJECT_TITLE: HSV/VZV chimeric viruses for identifying critical virus herpesvirus assembly interactions

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Pediatric;Prevention

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Deteriorations in glycemic control are common among adolescents with type 1 diabetes (T1D). Although family-based interventions are empirically supported to bolster disease management during this period, they are not widely implemented. The current study seeks to optimize family-based interventions for adolescents with T1D to provide a judicious, streamlined, and robust program to be implemented within diabetes care.

PI_NAMEs: WONG, JESSIE J. (contact)

PROGRAM_OFFICER_NAME: THORNTON, PAMELA L

PROJECT_TERMS: acceptability and feasibility;Adolescence;Adolescent;Adult;Age;Award;base;Behavior;behavioral health;biological development;Blinded;career;Caring;Child Rearing;Childhood diabetes;Clinic;Code;comparison group;Conflict (Psychology);contextual factors;Control Groups;Data;design;Deterioration;diabetes distress;diabetes management;Diabetes Mellitus;Disease Management;Distal;Enrollment;Ensure;experience;Family;Family Process;Focus Groups;follow-up;Foundations;Genetic Transcription;glucose monitor;glycemic control;Glycosylated hemoglobin A;Goals;Health;Health Services;improved;improved outcome;Individual;Insulin-Dependent Diabetes Mellitus;integrated care;intersectionality;Intervention;intervention effect;Intervention Studies;Intervention Trial;Knowledge;Link;Literature;Mediating;Mediation;Mental Depression;Mental Health;Mentored Patient-Oriented Research Career Development Award;Mentorship;Methodology;Modeling;multi-component intervention;Outcome;parental involvement;parental monitoring;Parents;Participant;Pathway interactions;patient outreach;patient screening;physical conditioning;prevent;primary endpoint;primary outcome;Process;programs;psychosocial development;Qualitative Methods;Quality of life;Randomized;randomized trial;Research;Resources;Risk;Sampling;satisfaction;Science;Scientist;secondary outcome;skills;Statistical Data Interpretation;Stress;Structure;therapy design;Time;Training;Videoconferencing;Waiting Lists;Youth

PROJECT_TITLE: Family Matters: Optimizing Family-Based Interventions for Adolescents with Type 1 Diabetes

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Bioengineering;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Cells respond to and control the tension of their plasma membrane by internalizing parts of their membrane through endocytosis, which regulates the number of receptors on the membrane. When this process is dysregulated, cells tend to lose the molecular identity of their membranes and become metastatic cancer cells, but the physical basis for this transition is not well-understood. This proposed project will combine live cell three-dimensional fluorescence microscopy with mathematical modeling to understand, on a molecular and mechanical level, how which cells regulate their membrane tension by bending and internalizing their plasma membranes during endocytosis.

PI_NAMEs: AKAMATSU, MATTHEW SATARO (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: 3-Dimensional;Actins;analytical tool;Apical;base;Binding;Biological Models;Biophysical Process;Biophysics;Bulla;Calibration;cancer cell;Cell membrane;cell motility;Cell Physiology;Cell Polarity;Cells;cellular imaging;Cellular Membrane;Characteristics;Chimeric Proteins;Classification;Classification Scheme;Clathrin;Collaborations;Complex;Computer Models;Cytoskeleton;Development Polarity;Diploidy;Disseminated Malignant Neoplasm;Endocytosis;endogenous stem cells;epithelial to mesenchymal transition;Event;experimental study;extracellular;Extracellular Fluid;Feedback;Fluorescence;fluorescence imaging;Fluorescence Microscopy;Foundations;Gatekeeping;Generations;glycosylation;human induced pluripotent stem cells;Image;induced pluripotent stem cell;inhibitor;interest;laboratory experiment;Lead;Light;live cell imaging;Machine Learning;machine learning method;mathematical model;Measures;Mechanics;Membrane;Methods;Microfilaments;Microscopy;Modeling;models and simulation;Molecular;Monitor;multi-scale modeling;Neoplasm Metastasis;novel;Osmosis;physical model;Physiological;Plasma Cells;polarized cell;polymerization;Polymers;post-doctoral training;Postdoctoral Fellow;predictive modeling;Process;protein biomarkers;protein function;Proteins;receptor;receptor internalization;recruit;Research;Role;simulation;Site;skills;spatiotemporal;stem cells;Stress;Surface;temporal measurement;Tertiary Protein Structure;Testing;theories;Training;Work

PROJECT_TITLE: Molecular and biophysical mechanism of plasma membrane internalization during nonclathrin endocytosis

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Rehabilitation;Schizophrenia;Serious Mental Illness

PHR: This study is designed to test the feasibility and effectiveness of a novel intervention, Motivation Skills Training (MST), for improving functional outcomes for people with a schizophrenia spectrum diagnosis. MST fills a critical gap in the available psychosocial approaches by teaching people how to regulate their own motivational state in the service of personal recovery goal attainment. The knowledge gained will inform the scope of evidence-based services needed to advance recovery outcomes for people with schizophrenia and schizoaffective disorder, and therefore alleviate a significant public health burden.

PI_NAMEs: SAPERSTEIN, ALICE M. (contact)

PROGRAM_OFFICER_NAME: HAIM, ADAM J

PROJECT_TERMS: acceptability and feasibility;Address;Adult;Aftercare;Age;Ambulatory Care Facilities;Behavior;Behavior Control;Belief;Client;Clinic;Clinical;Communities;community clinic;Control Groups;daily functioning;Data;Data Collection;design;Diagnosis;Education;Educational process of instructing;Effectiveness;effectiveness evaluation;effectiveness study;effectiveness testing;effectiveness trial;Employment;empowerment;Enrollment;evidence base;executive function;Feasibility Studies;feasibility testing;follow-up;Fostering;Functional impairment;functional improvement;functional outcomes;Funding;future implementation;Goals;Impairment;improved;Individual;Informal Social Control;Intervention;Knowledge;Life;Literature;Manuals;MASP2 gene;Measures;Mental Health;Methods;Modeling;Monitor;motivated behavior;Motivation;National Institute of Mental Health;New York;novel;Outcome;Outcome Measure;Outpatients;Participant;participant retention;Performance;Persons;pharmacologic;Phase;Pilot Projects;pleasure;primary outcome;Process;Provider;psychiatric symptom;psychosocial;Public Health;Quality of life;Randomized;Randomized, Controlled Trials;Recovery;Recovery of Function;recruit;Schizoaffective Disorders;Schizophrenia;schizophrenia spectrum disorder;Science;Self Direction;Services;Severities;skills;skills training;Source;Students;Symptoms;Techniques;Testing;Training;treatment comparison;treatment effect;uptake;Work

PROJECT_TITLE: Motivation Skills Training to Enhance Functional Outcomes for People with Schizophrenia


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because the discovery of mechanisms by which intestinal microorganisms influence dietary fat metabolism is expected to lead to increased understanding and new treatments for human obesity and undernutrition. The proposed research is therefore relevant to the part of NIH’s mission that pertains to developing fundamental new knowledge that will enhance health and reduce the burdens of illness.

PI_NAMEs: RAWLS, JOHN F (contact);YEN, CHI- LIANG ERIC

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: Ablation;absorption;Affect;Animals;Bacteria;Biological Assay;burden of illness;Carbohydrates;Cell Differentiation process;Cells;Cellularity;Chromatin;Chylomicrons;Colon;Consumption;Development;diet-induced obesity;Dietary Fats;Digestion;Disease;energy balance;Energy Intake;Energy Metabolism;Environmental Risk Factor;Enzymes;Epithelial Cells;Esterification;Fatty acid glycerol esters;fatty acid oxidation;Fatty Acids;Fermentation;Foundations;functional genomics;Gene Expression;Genetic;genetic analysis;Genetic Transcription;Germ-Free;Gnotobiotic;Goals;gut bacteria;gut microbiota;Health;High Prevalence;HNF4A gene;Homeostasis;host-microbe interactions;Human;human disease;improved;innovation;intestinal epithelium;Intestines;Knowledge;lipid metabolism;Lipids;Lipoproteins;Malnutrition;Mediating;Mediator;meetings;Metabolic;Metabolic Diseases;Metabolic Pathway;Metabolism;Microbe;microbial;microbial colonization;microbiota;microorganism;Mission;Mitochondria;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Nutrient;Obesity;Outcome;Physiological;Physiological Processes;Physiology;Predisposition;Process;Public Health;Regulation;Research;Resistance;response;Role;Ruminococcus;Signal Pathway;Small Intestines;Symbiosis;Testing;Time;Tissues;transcription factor;Triglycerides;United States National Institutes of Health;uptake;Zebrafish

PROJECT_TITLE: Microbial regulation of intestinal lipid metabolism and its physiological consequences

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DNPD-A(01)]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Dementia;Mental Health;Neurodegenerative;Neurosciences;Palliative Care

ORG_CITY: TEMPE

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: Project Narrative Bereaved AD/ADRD caregivers are at elevated risk for clinically pathological and subclinically problematic consequences and their numbers are increasing quickly. This proposal aims uses a model based on self- determination theory to understand the needs of bereaved AD/ADRD caregivers while accounting for the differences in the ways those needs are satisfied among key subgroups. The wider goal of this research is to use the understanding of bereaved AD/ADRD caregivers’ needs to create interventions to satisfy those needs, reducing the clinical and subclinical consequences of bereavement.

PI_NAMEs: BAKER, ZACHARY G (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: Address;Adult Children;Affect;Age;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Award;Bereavement;Caregivers;Clinical;clinical risk;cognitive interview;Communities;community advisory board;community organizations;Competence;coping;Dementia;Dementia caregivers;dementia caregiving;depressive symptoms;design;Development;Ensure;ethnic minority;Ethnic Origin;experience;Extended Family;Feedback;Funding;Future;Gender;Geographic Locations;Goals;Grief reaction;Impairment;innovation;Intervention;Interview;Leadership;Literature;Loneliness;Measures;medical specialties;member;Mentorship;Methods;Modeling;Motivation;novel;Outcome;outreach;Pathologic;Personal Growth;Personal Satisfaction;Persons;Phase;Physical Function;Process;programs;Public Health Schools;Qualitative Methods;Race;racial minority;recruit;Research;Research Personnel;Sampling;satisfaction;Science;Self Care;Self Determination;sex;Siblings;Source;Spouses;stakeholder perspectives;Structure;Subgroup;Surveys;Testing;theories;therapy development;Time;Training;United States National Institutes of Health;Work

PROJECT_TITLE: Addressing the Needs of Key Subgroups of Caregivers of Persons with Dementia After Loss Using Self-Determination Theory: A Mixed Methods Approach


ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it reveals new knowledge regarding the cause of brain aneurysms, a condition that leads to a high rate of disability and death in stroke patients upon rupture. In particular, our work for the first time identified the role of a novel degradation pathway that regulates the cell-matrix interaction in brain aneurysms and provides anti-degradation strategy as a novel therapy for treating the disease. Thus, the proposed research is relevant to the part of the NIH's mission that pertains to reducing the burdens of illness and disability.

PI_NAMEs: RUI, YANNING  (contact)

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: Affect;Affinity;Animal Model;Area;Autophagocytosis;Binding;Biological Assay;Blood Vessels;Brain Aneurysms;burden of illness;Cause of Death;Cells;cerebral artery;cerebrovascular;Cessation of life;Circle of Willis;Complex;Data;Degradation Pathway;Development;Digestion;disability;Disease;Endothelial Cells;Endothelium;Exhibits;experimental study;Extracellular Matrix;Focal Adhesions;gain of function;Genes;Genetic;Goals;Growth;Health;Hospital Costs;Impairment;improved;Incidence;innovation;Intracranial Aneurysm;Kinetics;knock-down;Knockout Mice;Knowledge;Life;Link;Mediating;Mission;Molecular;Morphology;mouse model;Mus;Names;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pharmacological Treatment;Phosphorylation;Play;preservation;prevent;Process;Public Health;receptor;receptor binding;Research;Resolution;Role;Rupture;Ruptured Aneurysm;Series;shear stress;single molecule;Stains;Stroke;stroke patient;Subarachnoid Hemorrhage;superresolution microscopy;Surgical Clips;System;Testing;therapeutic target;Time;United States National Institutes of Health;Variant;Vascular Permeabilities;vasodilator-stimulated phosphoprotein;Work;Zebrafish

PROJECT_TITLE: Role of Selective Autophagy of Focal Adhesion in Intracranial Aneurysm

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


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

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: Project Narrative TANK-binding kinase 1 (TBK1), a critical downstream effector of mutant active KRAS, is central to Axl- driven epithelial-mesenchymal transition (EMT) in KRAS-mutant Pancreatic Cancer (PDA); however, the mechanism of how TBK1 drives EMT has yet to be elucidated. I hypothesize that Axl-mediated TBK1 drives EMT via direct activation of AKT3 and the stability of downstream transcriptional networks. Despite significant research efforts, the function of EMT in metastasis has yet to be fully elucidated and metastatic cancers and relapse remain the primary cause of cancer related deaths; therefore my postdoctoral studies will be focused on understanding the molecular mechanisms underlying cellular plasticity, EMT, and metastasis to reveal novel strategies to target these programs for effective therapy for metastatic cancer. .

PI_NAMEs: BAKER, EMILY ARNER (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: AKT3 gene;Automobile Driving;axl receptor tyrosine kinase;Binding;Biological Assay;Cancer Biology;cancer cell;Cancer Etiology;cancer therapy;cancer type;Cell Line;cell motility;Cell Survival;Cells;Cessation of life;Chemoresistance;Chronic;combat;Data;Development;Disseminated Malignant Neoplasm;Distant;DNA Repair;DNA Sequence Alteration;effective therapy;epithelial to mesenchymal transition;Epithelium;Exhibits;experimental study;Fibroblasts;gain of function;Gene Amplification;Genetic Transcription;Glioma;Goals;Human;Immunofluorescence Immunologic;Immunoprecipitation;in vivo;Invaded;KRAS2 gene;Location;loss of function;Malignant Breast Neoplasm;Malignant Epithelial Cell;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mesenchymal;migration;Molecular;mutant;Mutation;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;Oncogenes;Organ;Organoids;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;Paracrine Communication;Pathway interactions;Patients;Pattern;Pharmaceutical Preparations;pharmacologic;Phenotype;Postdoctoral Fellow;Process;Prognosis;programs;protein expression;Protein Isoforms;Proteins;Proto-Oncogene Proteins c-akt;Publishing;Receptor Protein-Tyrosine Kinases;Relapse;Research;Resistance;response;Role;single cell sequencing;slug;TANK-binding kinase 1;Techniques;Technology;Therapeutic;Tissues;transcription factor;tumor;tumor microenvironment;tumor progression;tumorigenesis;Work

PROJECT_TITLE: Deciphering molecular mechanisms of Epithelial Plasticity


NIH_SPENDING_CATS: Cardiovascular;Childhood Obesity;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Dietary Supplements;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Indoor Air Pollution;Nutrition;Obesity;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Narrative This proposal allows US-China scientists to leverage resources and expertise on both sides to jointly advance environmental health research, with a focus on the inter-generational health effects of mercury, a persistent and widespread environmental pollutant with adverse impact around the globe. If successful, findings from this study will provide critically needed evidence to inform preconception, pregnancy and newborn risk assessment and primary prevention to reduce the adverse health effects of in utero Hg exposure, beginning at critical developmental windows when interventions may have the greatest life-long impact.

PI_NAMEs: WANG, GUOYING ;WANG, XIAOBIN  (contact)

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: 21 year old;Adult;Adverse effects;Affect;age group;Alcohol consumption;ambient air pollution;Animals;Anti-Inflammatory Agents;Antioxidants;bioaccumulation;Biological Markers;biological specimen archives;Birth;Blood Pressure;blood pressure elevation;Body mass index;Boston;Cardiometabolic Disease;cardiometabolic risk;cardiometabolism;Cardiovascular Diseases;cell growth;Chemical Exposure;Child;China;Clinical;cofactor;cohort;Collaborations;Conceptions;Data;Development;Diabetes Mellitus;Dietary intake;Disease;DNA Methylation;Dose;early onset;early pregnancy;Endothelium;Environmental Exposure;Environmental Health;Environmental Pollutants;Epidemic;Ethnic Origin;Exposure to;Fatty Acids;fetal;Fetal Development;Fetus;Fishes;Folic Acid;Food;Future;global health;Growth;Health;Homocysteine;Human;Hypertension;improved;in utero;Indoor Air Pollution;Inflammatory;insight;Insulin;intergenerational;Intervention;Investigation;Iron;Laboratories;Lead;Life;Lipids;Maternal Exposure;Measures;Mediating;Mercury;Meta-Analysis;Metabolic;metabolome;metabolomics;Metals;Methods;Micronutrients;Modeling;Modification;multi-ethnic;Neurotoxins;Newborn Infant;Non-Insulin-Dependent Diabetes Mellitus;novel;Nucleic Acids;Nutrient;nutrition;Obesity;offspring;Outcome;Overweight;overweight child;Passive Smoking;Pathway interactions;Placenta;Population;Pregnancy;Pregnancy Trimesters;prenatal;prenatal exposure;Primary Prevention;Procedures;Property;prospective;Public Health;Publishing;quality assurance;Quality Control;Race;repaired;Research;Research Design;Resources;response;Risk Assessment;risk mitigation;Role;Scientist;Seafood;Selenium;Side;Socioeconomic Status;Statistical Methods;Testing;Third Pregnancy Trimester;Time;Toxic Environmental Substances;Umbilical Cord Blood;Uterus;Vitamin B Complex

PROJECT_TITLE: Maternal Exposure to Low Level Mercury, Metabolome, and Child Cardiometabolic Risk in Multi-Ethnic Prospective Birth Cohorts

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-B(50)R]


ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative The ability to selectively incorporate heteroatom functionality into unactivated C–H bonds represents a significant advance in chemical synthesis. Developing functional mimics of the monooxygenase reactive intermediates will permit the generation of a new class of catalysts to effect C−H bond functionalization. Correlating the desirable functionality to the underlying electronic structure of reactive intermediates will provide new strategies for catalyst development.

PI_NAMEs: BETLEY, THEODORE A (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Trapping reactive intermediates and their application towards catalysis