ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE AML is a growing public health problem in the United States: over 20,000 new cases of AML will be diagnosed in 2019, and sadly, greater than 11,000 deaths will occur. Although routine use of dose-intense chemotherapy regimens improves outcomes for patients with AML, the majority of patients die of disease and suffer significant toxicities with therapy. As such, the development of more effective, molecularly-targeted therapies is of urgent clinical importance.

PI_NAMEs: CHALFANT, CHARLES E.;LOUGHRAN, THOMAS P. (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adjuvant;Adjuvant Therapy;Adult;Affect;Age;Apoptosis;Apoptotic;Biochemical;Biochemistry;Biodistribution;Bioinformatics;Biological;Biological Markers;Biophysics;Cell Line;Ceramides;Cessation of life;Chemotherapy-Oncologic Procedure;Clinical;Clinical Trials;clinical trials in animals;combinatorial;Cytotoxic Chemotherapy;Data;delivery vehicle;Development;Diagnosis;Diagnostic;Disease;Disease remission;Dose;Dose Limiting;Drug Delivery Systems;Drug Kinetics;Drug resistance;druggable target;efficacious treatment;efficacy evaluation;Ensure;Enzymes;experience;first-in-human;functional genomics;Funding;Genetically Engineered Mouse;Genomics;glycosylation;Goals;Heterogeneity;Human;improved;improved outcome;in vivo;Incidence;inhibitor;innovation;Investigation;Investigational Drugs;Left;leukemia;lipidomics;Lipids;Malignant Neoplasms;Memorial Sloan-Kettering Cancer Center;Metabolism;metabolomics;Molecular;molecular targeted therapies;nano;nanoliposome;nanoscale;new therapeutic target;Oncologist;Pathogenesis;patient derived xenograft model;Patient-Focused Outcomes;Patients;pharmacologic;Pharmacological Treatment;Phase;Phase I Clinical Trials;Phosphorylation;Population;pre-clinical;Pre-Clinical Model;preclinical trial;predictive marker;Predisposition;Process;prognostic indicator;Program Research Project Grants;programs;progression marker;Progression-Free Survivals;Proteomics;Protocols documentation;Public Health;Publishing;Refractory;Relapse;Resource Sharing;Review Committee;Sampling;Scientist;small molecule;Solid Neoplasm;Sphingolipids;Stable Disease;standard of care;synergism;System;Systems Biology;targeted agent;targeted treatment;Testing;Therapeutic;therapeutic target;therapy resistant;Toxic effect;Toxicology;Treatment Efficacy;tumor progression;United States;United States National Institutes of Health;Universities;Validation;Virginia

PROJECT_TITLE: Targeted Sphingolipid Metabolism for Treatment of AML


ADMINISTERING_IC: MH

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: AUSTIN

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PSYCHIATRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: PROJECT NARRATIVE Latinx children and adolescents experience rates of anxiety and related internalizing disorders at a higher rate than other ethnic groups, but we know little about risk and protective factors for the emergence of symptoms in Latinx children. This K01 will examine the role of neural, dyadic, and cultural markers of emotional processing and regulation in the development of anxiety symptoms in young Latinx children from toddlerhood to preschool. A greater understanding of the individual, dyadic, and cultural factors contributing to an increased risk for anxiety in Latinx children could have a substantial impact on our ability to identify which Latinx children are at the highest risk of starting trajectories towards clinical levels of anxiety and could help generate culturally- tailored interventions to modify developmental trajectories away from increased symptoms in these children.

PI_NAMEs: QUINONES-CAMACHO, LAURA  (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: 4 year old;5 year old;Adolescence;Adolescent;Adult;Age;Anxiety;Anxiety Disorders;anxiety symptoms;anxious;anxious behavior;Area;associated symptom;Biological;Biological Markers;Caregivers;Child;Childhood;childhood anxiety;Clinical;Communities;computerized data processing;Coupling;culturally appropriate intervention;Data;Data Analyses;Data Collection;Development;Discrimination;Disease;Distress;Electroencephalography;emotion regulation;Emotional;Emotions;Environment;Environmental Risk Factor;Ethnic Population;Event;Exclusion;experience;Family;Fright;Functional disorder;Goals;high risk;Income;Individual;Knowledge;Latinx;Life;life span;Link;Literature;Longitudinal Studies;Maps;Measures;Mediating;Mental disorders;Mentored Research Scientist Development Award;Mentors;Methodology;multidisciplinary;multimodality;National Institute of Mental Health;neural;neural correlate;Nursery Schools;Parents;Pattern;Play;Population;Process;programs;protective factors;Psychopathology;Regulation;Research;resilience;Rest;Risk;Risk Factors;Role;Sampling;satisfaction;Shapes;skills;social culture;Socialization;stressor;Symptoms;System;Techniques;Texas;Time;Training;Visit;Well in self;Work;Youth

PROJECT_TITLE: Neural, dyadic, and cultural influences on risk for anxiety in young Latinx children

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Nanotechnology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PROJECT NARRATIVE AML is the 2nd most common type of leukemia diagnosed and has a 5-year survival rate of only 27%. Unlike other non-solid tumors (e.g. CML), few significant improvements in AML survival have been achieved over the past 40 years, despite a large number of clinical trials using both conventional and targeted therapies. Of interest, the Bcl-2 inhibitor Venetoclax recently demonstrated improved clinical outcomes with conventional therapeutics, i.e., cytarabine (AraC) or hypomethylating agents. We posit that non-toxic liposomal-based therapeutics designed to deliver the pro-apoptotic bioactive lipid C6-ceramide will augment the efficacy of standard of care therapeutics and have a substantive clinical impact for the treatment of AML.

PI_NAMEs: CHALFANT, CHARLES E. (contact)

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Animal Model;Apoptotic;BCL2 gene;Biochemistry;Biological;Biological Markers;Biology;BIRC4 gene;cancer biomarkers;Cardiovascular Diseases;Cell Death;Ceramide glucosyltransferase;Ceramides;chemotherapy;Clinical;clinical application;Clinical Trials;cohort;combinatorial;conventional therapy;Cytarabine;Data;design;Diagnosis;diagnostic biomarker;dihydroceramide desaturase;Dose;Down-Regulation;Drug Kinetics;efficacious treatment;Enzymes;Exhibits;Funding;galactosylgalactosylglucosylceramidase;Goals;Grant;improved;In complete remission;In Vitro;in vivo Model;inhibitor;innovation;interest;leukemia;Licensing;Lipids;liposomal delivery;Liposomes;Maximum Tolerated Dose;MCL1 gene;Mediating;Memorial Sloan-Kettering Cancer Center;Metabolism;Molecular;N-caproylsphingosine;nano;nanoliposome;nanoscience;Outcome;Pathway interactions;Patients;Pharmacology;Phase;phase I trial;Pre-Clinical Model;prevent;Prognosis;prognostic;Prognostic Marker;Progression-Free Survivals;Proteins;Protocols documentation;Publishing;Refractory;Regimen;Relapse;Resources;Review Committee;Safety;Sampling;Site;Solid Neoplasm;Sphingolipids;sphingosine kinase;Stable Disease;standard of care;STAT3 gene;Survival Rate;synergism;targeted treatment;Testing;Therapeutic;Treatment Protocols;treatment response;treatment strategy;tumor;Universities;University of Virginia Cancer Center;Validation

PROJECT_TITLE: Clinical Trial of Ceramide nanoLiposomes in AML


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Hematology;Orphan Drug;Patient Safety;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: PROJECT NARRATIVE Race-ethnic disparities in acute leukemia clinical trial enrollment limit the generalizability of study findings and equitable access to high-quality care, while acute leukemia’s unique care patterns limit the utility of existing interventions to reduce them. I propose to combine community engagement with data science methods to develop a multilevel intervention targeting key trial enrollment barriers through three complementary pilot studies: a review system to preemptively modify trial design elements associated with enrollment disparities, an enrollment diversity performance feedback interface for physicians, and a peer-based support application for patients. Together, these interventions promise to create low-cost and scalable methods for diversifying cancer clinical trial enrollment as I prepare for an independent research career focused on ensuring equity in cancer care delivery.

PI_NAMEs: HANTEL, ANDREW  (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;Address;Adult;Affect;arm;Attitude;Behavior;Behavior Therapy;bilingualism;biomedical referral center;Black race;cancer care;Cancer Center;cancer clinical trial;Cancer Control;cancer health disparity;cancer type;care delivery;career;Caring;Catchment Area;Clinical Research;clinical trial enrollment;Communities;community advisory board;community based participatory research;community engagement;Complement;Complex;Comprehensive Cancer Center;cost;Data;data integration;Data Science;demographics;Disparate;Disparity;Educational Materials;Educational workshop;Electronic Health Record;Elements;empowerment;Enrollment;Ensure;Equity;ethnic disparity;ethnic diversity;Feedback;Focus Groups;Goals;health disparity;Hematopoietic Neoplasms;Hispanic;implementation science;Improve Access;improved;Incidence;Incubators;Inequity;innovation;Inpatients;Institution;Intervention;Intervention Trial;Knowledge;leukemia;Link;Lymphoblastic Leukemia;Malignant Neoplasms;marginalized population;Medical Records;Mentors;Methods;mobile application;model design;Modeling;Monitor;National Cancer Institute;neoplasm registry;novel;novel therapeutics;Outcome;Outpatients;Participant;patient-level barriers;Patients;Patterns of Care;peer;peer support;Performance;Persons;Physicians;Pilot Projects;Play;Policies;Population;Preparation;primary outcome;Protocols documentation;Provider;provider-level barriers;Qualitative Methods;Quality of Care;Race;racial disparity;randomized trial;Recommendation;Registries;Reporting;Research;Research Personnel;Research Proposals;Research Training;Risk;risk prediction;Safety;Scientist;secondary outcome;Services;Social Work;stem;Structure;success;System;Testing;therapy design;therapy development;tool;Training;trial design;trial enrollment;usability;Work

PROJECT_TITLE: Diversifying Acute Leukemia Clinical Trial Enrollment Through Multilevel Intervention

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Childhood Leukemia;Clinical Research;Hematology;Nanotechnology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PROJECT NARRATIVE This study focuses on the role of acid ceramidase in leukemic cell survival. Primary goals are to complete preclinical studies with novel acid ceramidase inhibitors and to identify clinical, biochemical, and genetic features that predict sensitivity to these agents. Knowledge gained from this work will be utilized to design improved AML treatments that exploit a novel target in specific patient populations.

PI_NAMEs: LOUGHRAN, THOMAS P. (contact)

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adult;Age;Age Years;aggressive therapy;Apoptosis;Apoptotic;BCL2 gene;Behavior;Biochemical;Biology;Caspase;Cell Line;Cell Survival;Cells;Ceramides;Chemoresistance;chemotherapy;Clinic;Clinical;clinical application;combinatorial;Data;design;Diagnosis;Disease;Disease Resistance;DNMT3a mutation;Dose;Drug Delivery Systems;drug development;Drug Kinetics;Enzymes;Exhibits;experience;FLT3 gene;Formulation;Funding;Future;galactosylgalactosylglucosylceramidase;Genes;Genetic;Genetically Engineered Mouse;genetically modified cells;Goals;Hematopoietic stem cells;Human;improved;In complete remission;in vivo;Individual;Induction of Apoptosis;inhibitor;knock-down;Knowledge;leukemia;leukemia treatment;Leukemic Cell;Link;Lipids;MCL1 gene;Mediator;Metabolism;metabolomics;Minority;Modeling;Molecular;Molecular Profiling;molecular subtypes;Molecular Target;mouse model;Mus;Mutation;Myelogenous;N-caproylsphingosine;nanoencapsulated;nanoliposome;non-genetic;novel;novel therapeutics;older patient;outcome prediction;overexpression;patient population;patient subsets;Patients;pharmacologic;Population;pre-clinical;preclinical efficacy;preclinical study;Preclinical Testing;Predisposition;prognostic;programs;Proliferating;Protein Isoforms;Proteins;Public Health;Regimen;Relapse;response;Role;Sampling;small molecule inhibitor;Sphingolipids;sphingosine 1-phosphate;standard of care;Standardization;success;synergism;System;targeted agent;targeted treatment;Technology;Testing;Therapeutic;Therapeutic Agents;Toxic effect;Translating;treatment strategy;Tumor Burden;Work;Xenograft Model

PROJECT_TITLE: Targeting Acid Ceramidase in AML


NIH_SPENDING_CATS: Bioengineering;Cancer;Childhood Leukemia;Clinical Research;Hematology;Nanotechnology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PROJECT NARRATIVE Acute myelogenous leukemia (AML), for which there have been few treatment advances in 40 years, is the most common type of acute leukemia in adults. There is a pressing need to improve treatment of AML, especially for the many that relapse and become drug-resistant. The goal of this work is to develop new, innovative, effective lipid-based therapies for treatment of AML.

PI_NAMEs: FISHER-WELLMAN, KELSEY H (contact)

PROJECT_TERMS: ABCB1 gene;Acceleration;Acute leukemia;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Adjuvant;Adult;analog;anti-cancer;anticancer activity;Antineoplastic Agents;Apoptosis;Apoptotic;Autophagocytosis;cancer cell;cancer therapy;Cell Death;Cell Line;Cell Survival;Cells;Ceramide glucosyltransferase;Ceramides;Chemoresistance;chemosensitizing agent;chemotherapy;Clinical;combinatorial;Cytarabine;cytotoxicity;Data;Daunorubicin;Disease;drug development;Drug resistance;Drug Targeting;effective therapy;Elements;Employment;Enzymes;Equilibrium;Fenretinide;galactosylgalactosylglucosylceramidase;Generations;Glucosylceramides;glycosylation;Goals;Golgi Apparatus;Growth;Human;improved;inhibitor;innovation;leukemia;leukemia treatment;Leukemic Cell;Lipids;Malignant Neoplasms;Membrane;Metabolic;Metabolism;Molecular;Multi-Drug Resistance;nanoliposome;Outcome;Patients;Permeability;Pharmaceutical Preparations;pharmacologic;Phenotype;Play;Pre-Clinical Model;pressure;programs;Property;refractory cancer;Regimen;Relapse;relapse patients;Research;Resistance;response;Role;Selection for Treatments;Sphingolipids;SPHK1 enzyme;Therapeutic;therapeutic target;therapeutically effective;Thinking;Time;treatment response;tumor progression;Tumor Suppressor Proteins;Valspodar;Work

PROJECT_TITLE: Targeting Ceramide Glycosylation in AML


ADMINISTERING_IC: AG

ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PI_NAMEs: PIKE, CHRISTIAN J (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Age;age acceleration;age related;Age-associated memory impairment;Aging;aging related;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease risk;anti aging;Apolipoprotein E;apolipoprotein E-3;Brain;clinical translation;combat;Data;design;Diet;dietary;dietary control;Dietary Intervention;efficacy testing;Energy Metabolism;Environment;Exhibits;Fasting;Female;Genes;Genotype;glial activation;Goals;Human;Impaired cognition;Impairment;improved;improved outcome;In Situ;in vitro Model;Inflammatory;Intervention;Ketones;Link;lipid metabolism;lipidomics;male;Metabolic;metabolic fitness;Methionine;middle age;Mitochondria;mortality;mouse model;Mus;N-formylmethionylphenylalanine;neural;novel;Nutritional;nutritional approach;Outcome;Outcome Measure;Pathogenesis;Pathology;Pathway interactions;Peptides;Phenotype;pre-clinical;prevent;Prevention;Property;Regulation;sex;Sex Differences;Shotguns;Signal Pathway;Testing;transcriptomics;Transgenes;TREM2 gene

PROJECT_TITLE: Dietary protection against APOE4 phenotypes in aging and Alzheimer's


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: BIRMINGHAM

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: HIV remains a deadly pathogen that threatens human's life and the absence of efficient cure poses a major problem for public health. Despite the success of antiretroviral therapy (ART), the emergence of drug resistant strains and the genetic diversity of HIV necessitates the development of even more potent and diverse ART. The proposed studies will advance our understanding of fundamental mechanisms in HIV-1 assembly and envelope incorporation, which may aid in the development of new strategies for antiviral drug design.

PI_NAMEs: SAAD, JAMIL SUBHI (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Affect;Amino Acids;Anti-viral Agents;antiretroviral therapy;Binding;Biochemical;CASP1 gene;Cell membrane;Complex;Cryo-electron tomography;Cryoelectron Microscopy;Cytoplasmic Tail;Data;design;Deuterium;Development;Drug Design;Drug resistance;env Gene Products;Funding;gag Gene Products;Genetic;Genetic Variation;Goals;HIV;HIV-1;Human;Hydrogen;Impairment;in vivo;Infection;innovation;Knowledge;Life;Lipids;Liposomes;Mass Spectrum Analysis;Mediating;Membrane;membrane assembly;Modeling;Molecular;Molecular Conformation;Mutation;myristoylation;N-terminal;novel;novel therapeutics;particle;pathogen;Phase;Phosphatidylinositols;Production;Proteins;Public Health;recruit;resistant strain;Resolution;Site;Structure;success;Techniques;Testing;Therapeutic Agents;Transmembrane Domain;Viral;Virion;Virus;Visualization;X-Ray Crystallography

PROJECT_TITLE: Structural Basis for HIV-1 Gag assembly and Env incorporation

STUDY_SECTION: HVCD

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


NIH_SPENDING_CATS: Bioengineering;Cancer;Nanotechnology

PHR: PROJECT NARRATIVE  Efficient management between performance sites is critical for success of this Program Project that will document dysfunctional sphingolipid metabolism and signaling as therapeutic targets in AML.

PROJECT_TERMS: Accountability;Advisory Committees;Animal Model;Bioinformatics;Biometry;Ceramides;Clinical;Clinical Trials;Collaborations;data sharing;Ensure;galactosylgalactosylglucosylceramidase;glycosylation;Goals;Institution;Laboratories;lectures;Legal patent;Manuscripts;meetings;Memorial Sloan-Kettering Cancer Center;Metabolism;metabolomics;Methodology;Modality;nanoliposome;Nanotechnology;New Hampshire;performance site;Principal Investigator;Productivity;Program Research Project Grants;programs;Progress Reports;Recommendation;Reporting;Resources;response;Signal Transduction;Sphingolipids;success;System;therapeutic target;United States National Institutes of Health;Universities;Virginia

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Clinical Research;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PROJECT NARRATIVE Acute myelogenous leukemia (AML) is the most common acute form of leukemia affecting adults, and it lacks long-term efficacious therapies. Core A serves a vital role in hypothesis testing and generation for the projects by seeking to understand alterations in (glyco)sphingolipid metabolism in AML by providing standardized measurements of the sphingolipid pathways and ADME/PK analytical services to facilitate sphingolipid-based therapy development. The outcome of these studies will help define new therapeutic strategies for AML.

PI_NAMEs: FOX, TODD E (contact)

PROJECT_TERMS: Acute;Acute leukemia;Acute Myelocytic Leukemia;Address;Adult;Affect;Age;Animal Model;Biological;Biostatistics Core;cancer type;Cell Line;Characteristics;Chemoresistance;Clinical;Cytogenetics;Data;design;Disease;Dose;Drug Delivery Systems;drug development;drug efficacy;Drug Kinetics;drug metabolism;efficacious treatment;efficacy study;Encapsulated;Enzymes;Etiology;FDA approved;Generations;Genetic;Goals;improved;improved outcome;in vivo;Incidence;insight;leukemia;Lipids;Liposomes;liquid chromatography mass spectrometry;Mass Spectrum Analysis;Measurement;Messenger RNA;metabolic abnormality assessment;Metabolism;metabolome;metabolomics;Methodology;Modification;Molecular;molecular targeted therapies;Morphology;Nature;novel;novel therapeutic intervention;Older Population;Outcome Study;Pathogenesis;Pathway interactions;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Phenotype;Polymers;Population;pre-clinical;Pre-Clinical Model;Preparation;Process;programs;Property;Public Health;Publishing;Quantitative Reverse Transcriptase PCR;Regimen;Resources;response;Role;Sampling;Services;Sphingolipids;Standardization;Survival Rate;System;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;therapy development;Transcript;Treatment Efficacy

PROJECT_TITLE: Targeted Sphingomics Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Genetics;Hematology;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE The overall goals of the present project are to study sphingolipid metabolism in AML and to design novel sphingolipid-based therapeutics for the treatment of AML. This Core will serve an essential role for all projects by maintaining a repository of human AML samples with defined clinical outcomes, as well as by developing robust murine models to test the efficacy of the Project’s sphingolipid-based AML therapeutics.

PI_NAMEs: CLAXTON, DAVID F (contact)

PROJECT_TERMS: 3-Dimensional;Aliquot;Alleles;Animal Model;Benchmarking;biobank;Biochemical;Biological;Biological Assay;Biology;Blood;Cell Culture Techniques;Cell Line;Cells;Ceramides;Characteristics;chemotherapy;Chemotherapy-Oncologic Procedure;Classification;Clinical;Clinical Data;clinical development;clinical material;Clinical Research;Clinical Trials;clinically relevant;Correlative Study;Cryopreservation;Cytogenetics;Data;Dependence;design;Disease;disorder subtype;DNA Library;Dose;Doxorubicin;Drug Kinetics;Eastern Cooperative Oncology Group;efficacy study;efficacy testing;efficacy trial;Elderly;Engraftment;Epigenetic Process;Exhibits;Frequencies;Gene Frequency;Genes;Genetic;genetic variant;Genetically Engineered Mouse;German population;Goals;Grant;Hematopoietic;Heterogeneity;Human;Human Resources;Immunocompetent;In Vitro;in vivo;Incidence;insight;Label;Laboratories;leukemia;leukemia tissue bank;Luciferases;Malignant Neoplasms;Maximum Tolerated Dose;Memorial Sloan-Kettering Cancer Center;Metabolism;Modeling;Molecular;molecular modeling;Molecular Profiling;molecular subtypes;Monitor;Morphology;mouse model;Mus;Mutate;Mutation;Myeloproliferative disease;nanoliposome;Neoplasms;novel;novel therapeutics;Outcome;Pathogenesis;patient derived xenograft model;Patients;Phase;Plasma;pre-clinical;preclinical efficacy;preclinical toxicity;Probability;programs;Protocols documentation;Publishing;Regimen;repository;Reproducibility;Research;Research Personnel;Resources;Review Committee;Role;Sampling;Services;Specimen;Sphingolipids;standard of care;success;System;Testing;Therapeutic;therapeutic development;therapeutic evaluation;Therapeutic Studies;Time;Tissue Banks;Toxic effect;Toxicokinetics;Translating;Transplantation;tumor;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Tissue Repository and Animal Models Core


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: CAMBRIDGE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: HARVARD UNIVERSITY

PHR: Project Narrative Episodic memory is important for numerous activities in everyday life, and disorders of episodic memory that impair everyday functioning are frequently observed in neurological disorders such as Alzheimer’s disease and amnesic syndromes, normal aging, and psychopathological conditions including depression and anxiety. The proposed research is highly relevant to public health because it focuses on understanding cognitive functions supported by episodic memory, such as future thinking and everyday problem solving, that are impaired in many clinical populations.

PI_NAMEs: SCHACTER, DANIEL L (contact)

PROGRAM_OFFICER_NAME: RANGEL GOMEZ, MAURICIO

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;angular gyrus;Anxiety;Autobiography;Behavioral;Behavioral Paradigm;Brain;Brain region;Clinical;Cognition;Cognitive;cognitive function;cognitive neuroscience;cognitive task;Collection;Common Core;Cues;Disease;Elements;Episodic memory;episodic memory impairment;Event;executive function;experience;experimental study;flexibility;Functional Magnetic Resonance Imaging;Future;Genetic Recombination;Goals;Hippocampus;Human;Impairment;innovation;insight;Knowledge;Life;Link;Location;Measures;Memory;Mental Depression;Methods;Nature;Nervous System Disorder;neural;neural patterning;neuroimaging;neuromechanism;normal aging;novel;novel strategies;Participant;Pattern;Persons;Play;Population;Problem Solving;Process;Public Health;recruit;Research;Retrieval;Rewards;Role;Semantics;Services;simulation;support network;Syndrome;Testing;Thinking;Time;Transcranial magnetic stimulation

PROJECT_TITLE: Event-related Neuroimaging of Human Memory Formation

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


NIH_SPENDING_CATS: Bioengineering;Cancer;Childhood Leukemia;Clinical Research;Data Science;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

PHR: PROJECT NARRATIVE The overall research team is collecting large, complex datasets from cancer patients, which must be analyzed comprehensively to inform critical decisions about the development of novel therapeutics. This shared resource core will act as a hub for individual research projects to combine their data types with those generated by others on the research team to make smarter choices about what targets to pursue in which patient subpopulations.

PI_NAMEs: JANES, KEVIN A (contact)

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Back;Biochemical Pathway;Biological;Biological Assay;Biological Markers;Cancer Model;Cancer Patient;Cell Line;Ceramides;Classification;Clinical;cohort;complex data;Cytogenetics;cytotoxic;Data;Data Analyses;data integration;Data Set;Decision Making;Descriptor;Development;drug development;drug discovery;Drug Targeting;enzyme activity;Enzyme Inhibition;Enzymes;experience;follow-up;Gene Mutation;gene product;Genes;Genetic;Goals;Head;heterogenous data;Human;human disease;human model;Hydrolysis;Individual;innovation;Leadership;Least-Squares Analysis;leukemogenesis;lipidomics;Lipids;Measurement;Mediating;Metabolism;metabolomics;Modeling;Molecular Profiling;multidimensional data;multiple data types;Mutation;nanoliposome;network models;novel marker;novel therapeutics;Outcome;Pathway interactions;patient stratification;patient subsets;Patients;pharmacologic;preclinical development;predicting response;predictive modeling;programs;Proportional Hazards Models;prospective;Reaction;reconstruction;Recurrence;Regulation;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;response;Sampling;Services;Somatic Mutation;Source;Sphingolipids;standard of care;System;Systems Biology;targeted treatment;Testing;Training;Transcript;translational impact;Validation

PROJECT_TITLE: Systems Metabolomics Core


ADMINISTERING_IC: GM

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: The Medical Science Training Program (MSTP) at the Medical College of Wisconsin (MCW) provides integrated basic science and medical training as the educational foundation for future academic physician scientists. The mission of MCW-MSTP is to prepare students for careers as physician-scientists, which allows students to conduct hypothesis-driven research and to practice evidence-based medicine as an MD-PhD. MCW-MSTP welcomes all applicants, including students of diversity, students with disabilities, and students from socio-economically disadvantaged backgrounds.

PI_NAMEs: BARBIERI, JOSEPH T;SALZMAN, NITA H (contact)

PROGRAM_OFFICER_NAME: AIYEGBO, MOHAMMED S

PROJECT_TERMS: Medical;Scientist;Training Programs

PROJECT_TITLE: Medical Scientist Training Program

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Cancer;Clinical Research

PHR: PROJECT NARRATIVE Biostatistics and data management support are critical for the success of the Program Project, which involves human subjects, animal models, and approximately 30 different hAML cell lines. The Biostatistics Core provides easy and guaranteed access for investigators and also allows the biostatisticians to specialize in the Project areas regarding content knowledge and appropriate statistical methodology. The dedicated and experienced personnel in the Core provide the resources and support available to all investigators in the Program Project, and the Core serves as the interface to the larger resources in biostatistics in the Department of Public Health Sciences (DPHS) of the School of Medicine at the University of Virginia.

PI_NAMEs: HORTON, BETHANY JABLONSKI (contact)

PROJECT_TERMS: Address;Animal Model;archive data;Area;Biometry;Biostatistics Core;Cell Line;Clinical;Collaborations;Data;Data Analyses;data management;data repository;data sharing;Dedications;design;Ensure;experience;Experimental Designs;experimental study;Goals;Health Sciences;Human Resources;human subject;improved;insight;Knowledge;Laboratories;Manuscripts;medical schools;Metabolism;Methodology;Methods;Modeling;multiple data sources;novel;Patient-Focused Outcomes;Patients;Preparation;preservation;programs;Public Health;Research;Research Design;Research Personnel;Resources;Sample Size;Sampling Studies;Services;Source;Specific qualifier value;Sphingolipids;success;synergism;Technology;Testing;tool;Universities;Variant;Virginia

PROJECT_TITLE: Biostatistics Core


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes

ORG_CITY: SALT LAKE CITY

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE To accelerate the pace of diabetes research, there is a pressing need to train computational scientists the biological basis of diabetes and related metabolic disorders. The University of Utah Computational Approaches to Diabetes and Metabolism Research Training Program trains both predoctoral and postdoctoral trainees in the computational and mathematical sciences and in the biological basis of diabetes and obesity. These bioinformatics scientist trainees will gain the expertise and leadership skills to apply computational methods to complex biological questions that will ultimately impact the prevention, treatment, and outcomes of people with diabetes and related metabolic diseases.

PI_NAMEs: EILBECK, KAREN LOUISE (contact);PEZZOLESI, MARCUS GUY

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TITLE: University of Utah Interdisciplinary Training Program in Computational Approaches to Diabetes and Metabolism Research

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: IRVINE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE Transposable elements are prevalent selfish DNA sequences present in many organisms, and they constitute about 45% of the human genome. Their activity and abundance are related to their ability to cause inherited diseases and cancers, including breast cancer, colon cancer, and leukemia. The proposed research will identify factors that influence the abundance of transposable elements and determine their consequences on host function and fitness, with strong implications for human health and disease states.

PI_NAMEs: LEE, GRACE YUH CHWEN (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: 3-Dimensional;Affect;Biochemical;Cellular biology;chromatin modification;Colon Carcinoma;comparative;Disease;DNA;DNA Insertion Elements;DNA Sequence;DNA Transposable Elements;Drosophila genus;Epigenetic Process;Evolution;Exhibits;Fertility;fitness;Genes;Genetic;Genetic Processes;Genome;genome-wide;Genomics;Goals;Health;Hereditary Disease;Human;Human Genome;Inherited;Laboratories;leukemia;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Modeling;Molecular;novel;Nuclear;Organism;Parasites;Persons;Positioning Attribute;programs;Research;RNA;Role;Salamander;Selfish DNA;Shapes;species difference;Structure;Tetraodontidae;Variant;vertebrate genome

PROJECT_TITLE: How transposable elements drive genome evolution through epigenetic mechanisms

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: PORTLAND

ORG_DEPT: NEUROLOGY

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Glial cells, the primary immune responders in the brain, respond swiftly to neurodegeneration, and abnormal innate immune responses are coupled to the progression of devastating neurological conditions, as well as poor recovery from acute traumatic events. This proposal is relevant to public health because it will provide critically needed insight into the molecular and cellular signaling pathways that govern glial responses to neural injury. These discoveries will advance our understanding of neuron-glia communication in the brain, provide a springboard for the development of treatments to reduce the burden of neurological disorders and, thus, will be highly relevant to the NIH mission.

PI_NAMEs: LOGAN, MARY ALLISON (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Acute;Adult;Affect;Astrocytes;Axon;axon injury;axonal degeneration;Axotomy;Biological Assay;Biological Models;Brain;brain health;Calcium;Calcium Oscillations;cell motility;Cells;Chronic;cohort;Communication;Communities;confocal imaging;Coupled;Cues;Cytoskeleton;Data;Defect;Degenerative Disorder;Dense Core Vesicle;Drosophila genus;Drosophila melanogaster;Ensure;Event;Excision;Fluorescence;Fluorescent in Situ Hybridization;fly;Gene Expression;Gene Expression Profiling;Genes;genetic manipulation;Genetic Models;Genetic Transcription;high resolution imaging;imaging modality;Immune;Immune response;Immunity;Immunologic Factors;immunoreaction;immunoregulation;in vivo;in vivo monitoring;Infiltration;Inflammation;Injury;Innate Immune Response;insight;Insulin;insulin-like signaling;Label;Ligands;Matrix Metalloproteinases;Messenger RNA;Methods;migration;Mission;Modeling;Molecular;molecular subtypes;Monitor;Motility;Nerve;Nerve Degeneration;nerve injury;Nervous System;Nervous System Disorder;Neuroglia;Neurologic;Neurons;Neuropeptides;neuroprotection;neurotoxic;neurotransmission;novel;Olfactory Pathways;Organism;Peripheral;Phagocytes;Play;Process;programs;Public Health;Reaction;receptor;Recovery;Reporter;response;Ribosomal Interaction;Role;Signal Pathway;Signal Transduction;single molecule;Site;Stress;Synaptic plasticity;System;Techniques;therapy development;Transcript;transcriptome sequencing;Translating;Translations;Trauma;traumatic event;United States National Institutes of Health;Up-Regulation;vesicular release;Visualization;Wallerian Degeneration;Wing;Work

PROJECT_TITLE: Exploring the Role Dense Core Vesicle Release in Glial Immunity

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Infectious Diseases;Inflammatory Bowel Disease

ORG_CITY: RIVERSIDE

ORG_DEPT: ZOOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: Project Narrative Nematodes are successful and devastating parasites of humans, capable of modulating host biology in numerous ways including suppressing the immune system. The goal of my lab is to understand modulation of host biology by nematode parasites, and to characterize the host signaling pathways they target to achieve this modulation. This research project contributes to our understanding of lipid signaling in innate immunity and how nematode proteins affect host immunity.

PI_NAMEs: DILLMAN, ADLER RAY (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Affect;Autoimmune Diseases;Binding;Biological Models;Biology;Celiac Disease;Cells;Crohn's disease;Drosophila genus;Drosophila melanogaster;Drug resistance;Eicosanoids;Evolution;Fatty Acids;Genetic;Genetic Models;Goals;Health;Human;Immune response;Immune signaling;Immune system;Immunity;immunoregulation;Immunosuppression;in silico;In Vitro;in vivo;Infection;Inflammatory Bowel Diseases;Learning;Lipids;Mediating;member;Modeling;Molecular;Morbidity - disease rate;mortality;Natural Immunity;Nematoda;Nematode infections;novel;novel therapeutic intervention;Outcome;Parasites;Parasitic nematode;Pathology;Pathway interactions;Population;Prevalence;Protein Family;Protein Secretion;Proteins;recurrent infection;Research;Research Project Grants;Retinol Binding Proteins;Signal Pathway;Signal Transduction;small molecule;Source;success;Tissues;vaccination strategy

PROJECT_TITLE: Molecular mayhem: Immune modulation and eicosanoid signaling during infection

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Disability Research;Mental Health;Networking and Information Technology R&D (NITRD);Pain Research;Palliative Care;Prevention;Rehabilitation;Telehealth

ORG_CITY: OKLAHOMA CITY

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: PROJECT NARRATIVE Chronic pain, a common and distressing complication of advanced cancer, is commonly treated with analgesics with minimal access to comprehensive biopsychosocial pain management approaches. Aligning with NCI’s mission to advance scientific knowledge to help patients live longer, healthier lives, this K08 proposal seeks to improve cancer patients’ pain self-management by adapting and integrating cognitive behavioral therapy for pain into an existing mHealth intervention designed to optimize pharmacologic management (e.g. daily pain/opioid monitoring and tailored advice) for patients with advanced cancer. This integrated psychological and pharmacologic mHealth intervention has strong potential to improve cancer pain outcomes and to readily disseminate pain management support and alleviate pain for a wide range of patients with advanced cancer.

PI_NAMEs: HILTON, DESIREE R (contact)

PROJECT_TERMS: acceptability and feasibility;Active Learning;Advanced Malignant Neoplasm;Advisory Committees;Affect;Algorithms;Analgesics;Attention;Award;Behavior;Behavior Therapy;Behavioral;behavioral clinical trial;Behavioral Model;Behavioral trial;biopsychosocial;Cancer Intervention;cancer pain;Cancer Patient;Cancer Survivor;cancer therapy;Cellular Phone;Chronic Cancer Pain;chronic pain;chronic pain management;chronic pain patient;Clinical Trials;Cognitive Therapy;Complication;Constipation;Coping Skills;curative treatments;daily pain;Data;Data Analytics;Dedications;design;Development;digital healthcare;disability;Distress;Doctor of Philosophy;Ecological momentary assessment;Education;effective therapy;efficacy study;efficacy trial;Emergency Situation;Exercise;experience;Fatigue;Feasibility Studies;feasibility testing;Funding;Future;Goals;Health Technology;improved;Intervention;intervention refinement;Intervention Studies;Interview;Knowledge;Learning;Life;longitudinal analysis;Malignant - descriptor;Malignant Neoplasms;Measures;Medical;Medication Management;Mentors;Mentorship;Methods;mHealth;mhealth interventions;Mission;mobile application;Mobile Health Application;Monitor;Moods;Multimedia;negative mood;non-cancer chronic pain;novel;Online Systems;Opioid;opioid use;Pain;pain catastrophizing;Pain intensity;Pain interference;Pain management;pain outcome;pain relief;pain self-management;palliate;Palliative Care;patient subsets;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;pilot trial;Population;Preparation;programs;psychoeducation;psychologic;Psychological Factors;Psychology;Quality of life;Randomized;randomized, clinical trials;recruit;Relaxation;Research;Research Activity;research faculty;Research Personnel;retention rate;Scientific Advances and Accomplishments;secondary outcome;Secondary pain;Sedation procedure;Self Efficacy;Self Management;Self-reflection;Series;Service delivery model;Severities;side effect;skills training;smartphone application;Solid;Stress;Structure;Surveys;Symptoms;Target Populations;Technology;telehealth;Testing;therapy design;therapy development;Time;Training;Training Programs;treatment as usual;treatment duration;trial design;United States National Institutes of Health;Video Recording;Visit;Work

PROJECT_TITLE: Integrating pain-CBT into an mHealth analgesic support intervention for patients with chronic pain from advanced cancers


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Heart Disease;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Women's Health Research

ORG_CITY: IOWA CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE Women who develop gestational diabetes during pregnancy are two times more likely to develop cardiovascular disease and 7 times more likely to develop type 2 diabetes in the decade after pregnancy, but the reason why this occurs is unclear and there are currently no specific treatment strategies to prevent this disease progression. This project addresses this public health issue in three ways: examining if woman with a history of gestational diabetes have reduced micro-vessel responses to insulin (aim 1), delineating if oxidative stress is the cause of this reduced function and where this oxidative stress is coming from (aim 2), and examining if metformin treatment after pregnancy is able to specifically reverse this micro-vessel dysfunction (aim 3). Answering these questions will increase our understanding of what causes elevated disease risk after gestational diabetes and lay the foundation for trials of mechanism-specific treatment and prevention strategies in these women with high lifetime cardiovascular and metabolic disease risk.

PI_NAMEs: STANHEWICZ, ANNA  (contact)

PROGRAM_OFFICER_NAME: VARAGIC, JASMINA

PROJECT_TERMS: Acceleration;Acetylcholine;Acute;Address;Animals;Attenuated;attenuation;Biochemical;Biopsy;Blood capillaries;Blood Vessels;Cardiovascular Diseases;cardiovascular disorder risk;Cells;Chronic;Clinical;clinical translation;Clinical Treatment;Coupled;Cutaneous;Data;Development;Disease;Disease Progression;Disease Resistance;disorder risk;Dissection;efficacy testing;Endothelial Cells;Endothelium;experimental study;Foundations;Functional disorder;Future;Gestational Diabetes;Goals;high risk;Human;improved;in vivo;innovation;Insulin;Insulin Resistance;insulin sensitivity;Intervention;Mediating;Metabolic Diseases;Metformin;Microcirculation;Microvascular Dysfunction;Modeling;Molecular;NADP;NADPH Oxidase;Nitric Oxide;Non-Insulin-Dependent Diabetes Mellitus;novel;Onset of illness;Oxidases;Oxidative Stress;Patients;pharmacologic;post pregnancy;pre-clinical;Pregnancy;Pregnancy Complications;prevent;Prevention strategy;preventive intervention;programs;Public Health;Reactive Oxygen Species;Recording of previous events;recruit;Research;response;Risk;risk mitigation;Role;Source;therapeutic evaluation;therapeutic target;Translational Research;treatment strategy;vascular bed;Vascular Diseases;vascular endothelial dysfunction;Vascular Endothelium;Vasodilation;Woman;Women's cohort;Work

PROJECT_TITLE: The role of oxidative stress in reduced microvascular function after gestational diabetes

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences

ORG_CITY: CHESTNUT HILL

ORG_NAME: BOSTON COLLEGE

PHR: Project Narrative. There is an unmet clinical need for effective anxiety disorder treatments. The brainstem has been overlooked as a source of threat computation and a locus of dysfunction in disorders. This proposal will rigorously reveal threat signaling, prediction error computation, and specific fear behavior organization by brainstem networks: knowledge essential to developing effective anxiety disorder treatments.

PI_NAMEs: MCDANNALD, MICHAEL A (contact)

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Amygdaloid structure;Anxiety Disorders;Area;Behavior;Behavioral;Brain;Brain Stem;Clinical;conditioned fear;Cues;Data;density;Dependence;designer receptors exclusively activated by designer drugs;Discrimination;Disease;Dorsal;effective therapy;Equation;Female;fluorophore;Foundations;Freezing;Fright;Functional disorder;genetic manipulation;Implant;Infusion procedures;Injections;innovation;Interruption;Knowledge;Laboratories;Learning;learning network;Link;Locomotion;male;midbrain central gray substance;Mus;neural;neural circuit;Neurons;optogenetics;Outcome;Output;Phase;Play;Probability;Procedures;Prosencephalon;Rattus;Role;Shapes;Shock;Signal Transduction;Source;Testing;treatment of anxiety disorders;Update;Virus

PROJECT_TITLE: Brainstem-forebrain networks and threat computation

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


ORG_CITY: DAVIS

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The proposed studies in this K01 application promise to greatly expand our understanding of PARP inhibitor function and the development of resistance to these drugs. This knowledge may lead to enhanced treatment strategies and methods to both expand the utility of PARP inhibitors and the efficacy which they produce. Thus, completion of this work may prolong survival of critically ill patients.

PI_NAMEs: LOMBARD, ALAN  (contact)

PROGRAM_OFFICER_NAME: WALI, ANIL

PROJECT_TERMS: Address;advanced prostate cancer;androgen independent prostate cancer;Apoptosis;Biochemical;Cancer Patient;CDC2 gene;Cell Cycle;Cell Cycle Checkpoint;Cell Death;Cell Line;Cell Maintenance;cell repository;Cell Survival;Cells;Cessation of life;Clinical Oncology;clinical translation;Clinical Treatment;clinically relevant;Critical Illness;cytotoxicity;Data;Defect;Development;Disease;disease model;DNA Damage;DNA Repair;Drug resistance;Drug usage;Educational workshop;Environment;Exhibits;experience;experimental study;expression vector;Faculty;FDA approved;Fostering;G2/M Arrest;G2/M Checkpoint Pathway;Gene Mutation;gene repair;Genomics;Goals;Grant;homologous recombination;homologous recombination deficiency;IGFBP3 gene;improved;in vivo;interest;Knowledge;Lead;Link;LNCaP;M cell;Maintenance;Malignant neoplasm of prostate;Mediating;Mentored Research Scientist Development Award;Mentors;Methods;Modeling;Monitor;neoplastic cell;novel;novel therapeutics;overexpression;PARP inhibition;patient subsets;Patients;Pharmaceutical Preparations;Phase;Phenotype;Poly(ADP-ribose) Polymerase Inhibitor;Positioning Attribute;potential biomarker;pre-clinical;Principal Investigator;prostate cancer cell;prostate cancer cell line;prostate cancer model;Prostate Cancer therapy;Proteomics;repository;Research Personnel;Resistance;Resistance development;Resources;response;RNA Interference;Role;senescence;senescence associated secretory phenotype;senescent cell;Signal Transduction;Single Strand Break Repair;Stress;success;Techniques;Testing;Therapeutic;TP53 gene;Training;Training Activity;transcriptomics;treatment response;treatment strategy;tumor;tumor progression;Up-Regulation;Work;Writing

PROJECT_TITLE: Defining PARP Inhibitor Response and Resistance in Prostate Cancer


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Microbiome;Nutrition;Pediatric;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: NARRATIVE We will examine mechanisms of impaired oral tolerance due to cryptosporidiosis in neonatal animals. These studies may help explain the long-term growth stunting that is associated with early cryptosporidiosis infection in humans.

PI_NAMEs: SIBLEY, L. DAVID (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Adult;Age;age related;Antigens;Architecture;Automobile Driving;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Child;Clinical;Colon;community-level factor;Complex;Cryptosporidiosis;Cryptosporidium;Cryptosporidium parvum;Defect;Developing Countries;Development;diarrheal disease;dietary;Dietary Factors;Disease;dysbiosis;enteric infection;Environment;Failure to Thrive;Food;food antigen;FOXP3 gene;Goblet Cells;Growth;Height;Human;IL18 gene;Immune response;Impairment;Individual;Infant;Infection;Inflammation;Intestines;Knowledge;Life;Livestock;Maintenance;Malnutrition;mesenteric lymph node;microbial community;microbiome;microbiota;Molecular;Morbidity - disease rate;mortality;mouse model;Mucosal Immune System;Mucosal Immunity;Mucous Membrane;Mus;Neonatal;neonatal infection;neonatal mice;Newborn Animals;old mice;Oocysts;Oral;oral tolerance;Organism;Outcome;Peripheral;Play;Predisposition;Prevalence;prevent;Primary Infection;Process;Production;Regulatory T-Lymphocyte;response;Role;Sampling;Shapes;Signal Transduction;Testing;Time;Villus;Weight;Zoonoses

PROJECT_TITLE: Cryptosporidiosis and Oral Tolerance

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: American Indian or Alaska Native;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Depression;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Major Depressive Disorder;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Pregnancy;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Serious Mental Illness;Social Determinants of Health;Telehealth;Women's Health Research

ORG_CITY: DENVER

ORG_NAME: UNIVERSITY OF DENVER (COLORADO SEMINARY)

ORG_STATE: CO

PHR: NARRATIVE Postpartum depression is a significant public health concern, as at least 1 in 7 individuals will experience postpartum depression and alarming related health disparities exist, both in rates of postpartum depression and in availability of efficacious treatment. This project has clear relevance, affecting this significant mental health problem by determining whether an established preventive intervention (group interpersonal psychotherapy) delivered virtually shows the same benefits for preventing postpartum depression as it does in person. Recommendations based on this study will support sustainability and scalability of the intervention to other healthcare settings.

PI_NAMEs: DAVIS, ELYSIA POGGI;RHOADES, GALENA  (contact)

PROGRAM_OFFICER_NAME: CHU, SERENA PO-LAN

PROJECT_TERMS: 37 weeks gestation;access disparities;Address;Adoption;Affect;African American;Alaska Native;American Indians;Area;Birth;Black American;Characteristics;community setting;cost;Data;Depression screen;depressive symptoms;design;Developmental Delay Disorders;Diagnosis;Discipline of obstetrics;Discrimination;Economically Deprived Population;Effectiveness;effectiveness testing;effectiveness trial;efficacious intervention;efficacious treatment;Electronic Health Record;Enrollment;Ethnic Origin;evidence base;experience;future implementation;Gestational Age;Health;health care service utilization;health care settings;health disparity;Health Services;Health Services Accessibility;Health Surveys;Health system;Healthcare;Hispanic;Hospitals;implementation outcomes;implementation process;Individual;interpersonal therapy;Intervention;intervention cost;intervention program;Latinx;Link;Medicaid;Mental Depression;Mental Health;Minority Groups;Modeling;Mothers;neighborhood safety;next generation;obstetric care;Outcome;Patients;people of color;Perinatal;perinatal complications;perinatal health;peripartum depression;Persons;Population;Postpartum Depression;Postpartum Period;Predictive Factor;Pregnancy;pregnant;Pregnant Women;Premature Birth;prenatal;Prenatal care;prevent;Prevention;Prevention program;preventive intervention;Proctor framework;Program Sustainability;programs;Psychopathology;Public Health;Qualifying;Race;Randomized;Randomized, Controlled Trials;Recommendation;Research;safety net;screening;Service delivery model;service providers;Services;social stigma;Social support;sociodemographic factors;socioeconomic disadvantage;Spanish/English;standard of care;Stress;Surveys;telehealth;Testing;Underserved Population;Uninsured;United States Preventative Services Task Force;Videoconferencing;virtual;virtual delivery;virtual group;virtual intervention;Women's Health

PROJECT_TITLE: Group-based Prevention of Postpartum Depression: In-person vs. Virtual Delivery


ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Atrial fibrillation (AF) is the most common abnormal heart rhythm, affecting >3 million Americans and may lead to bothersome symptoms including palpitations, congestive heart failure and stroke. Our proposal seeks to determine whether chronic premature atrial contractions (PACs) cause adverse atrial electrical and structural remodeling and contribute to the development of AF over time. If our hypothesis is correct, it could lead to a novel upstream preventive therapy for AF, improving quality of life, reducing morbidity and mortality and reducing healthcare costs for many Americans.

PI_NAMEs: GERSTENFELD, EDWARD PAUL (contact)

PROGRAM_OFFICER_NAME: SOPKO, GEORGE

PROJECT_TERMS: Ablation;Affect;Age;American;Atrial Fibrillation;Atrial Premature Complexes;Benign;Calcium;Cardiac ablation;Cardiomyopathies;cardiovascular health;Case/Control Studies;Chronic;Clinic;Congestive Heart Failure;Coupled;Coupling;Data;density;Development;Early Intervention;Echocardiography;Electrophysiology (science);experience;experimental study;Fibrosis;Framingham Heart Study;Future;Health Care Costs;Heart Abnormalities;Heart Atrium;Heart failure;heart rhythm;hemodynamics;Histology;Holter Electrocardiography;Hour;Human;improved;Individual;Laboratories;Lateral;Lead;Left;Left atrial structure;lifestyle factors;Link;Maintenance;Maps;Measurement;Mediating;Medical;Molecular;Molecular Profiling;Morbidity - disease rate;mortality;Myopathy;novel;Palpitations;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Pirfenidone;porcine model;prevent;Prevention;Preventive therapy;Prospective, cohort study;Pulmonary veins;Quality of life;Recurrence;Research;Research Personnel;Risk;Series;Shortness of Breath;Source;Stress;Stroke;Symptoms;Testing;Time;Tissues;transcriptome sequencing;Ventricular;Ventricular Premature Complexes;Work

PROJECT_TITLE: Elucidating Mechanistic Relationships Between Atrial Ectopy, Atrial Remodeling and Atrial Fibrillation


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: CHARLESTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Opioid use disorder (OUD) is a complex multi-symptomatic disorder whereby traits non-linearly interact on an individual basis across the OUD phases influencing vulnerability and resiliency. Using a novel rat model capturing this behavioral heterogeneity present in human OUD, cell- and pathway- specific adaptions underlying OUD propensity will be characterized. Work from this proposal will contribute to disentangling the neurobiological and behavioral complexities associated with OUD vulnerability, yielding valuable insight into the compensatory mechanisms in place to promote resiliency.

PI_NAMEs: KUHN, BRITTANY NICOLE (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: addiction;Affect;Attenuated;Behavior;Behavioral;Behavioral Model;behavioral phenotyping;career;Cells;Characteristics;Cluster Analysis;Complex;Confocal Microscopy;Cues;Dendrites;Dendritic Spines;density;Development;Diameter;Disease;Drug Regulations;drug seeking behavior;Electrophysiology (science);experimental study;Female;FOS Protein;functional plasticity;Genetic;genetic approach;genetic technology;Globus Pallidus;Habenula;Head;Heroin;heroin use;Heterogeneity;Human;human model;Immunohistochemistry;Individual;individual variation;insight;Label;Lateral;Link;male;Measures;Mediating;Modeling;Morphology;N-Methylaspartate;network models;Network-based;neural circuit;neurobiological mechanism;Neurobiology;Neuronal Plasticity;Neurons;novel;Nucleus Accumbens;opioid use disorder;optogenetics;Output;patch clamp;Pathway interactions;Phase;Phenotype;Population;postsynaptic;Prediction of Response to Therapy;Process;promote resilience;protein biomarkers;Rattus;Regulation;Relapse;Reporter;resilience;response;Rewards;Rodent Model;Signal Transduction;Structure;Structure of subthalamic nucleus;Substance Use Disorder;Symptoms;Synaptic Potentials;Techniques;Testing;Tracer;Training;trait;Treatment Efficacy;United States;Vertebral column;Viral;Work

PROJECT_TITLE: Neurobiological mechanisms underlying resiliency and vulnerability to opioid use disorder

STUDY_SECTION: NIDA

STUDY_SECTION_NAME: Career Development Education and Training Study Section[NIDA-K]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: ATHENS

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Project Narrative Cell multinucleation is essential for the development and function of multiple types of human tissues. Despite the significance, we know little about the mechanism that controls the behavior and fitness of multinucleated cells. Our study will fill this critical knowledge gap, and ultimately provide a basis to treat human diseases where multinucleated cells malfunction.

PI_NAMEs: BI, PENGPENG  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Animals;Award;Behavior;Behavior Control;Biochemical;Biological;Body System;cancer cell;Cardiac Myocytes;Cell Communication;Cell Nucleus;cell type;Cells;cellular engineering;Cellularity;Communities;Development;Environment;fascinate;fitness;Gene Expression;gene function;Genetic;Genomics;Giant Cells;Homeostasis;Human;human disease;human tissue;Imaging technology;in vivo;innovation;intercellular communication;Investigation;Knowledge;Messenger RNA;Methodology;Modeling;Mononuclear;Muscle;Nature;Polyploidy;programs;Research;response;Retinal blind spot;Reverse engineering;single cell genomics;single molecule;Stimulus;Syncytiotrophoblast;System;Techniques;Technology;Tissues;trafficking;transcriptomics

PROJECT_TITLE: Spatial genetics investigation of multinucleated cells

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Networking and Information Technology R&D (NITRD)

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: Project Narrative The proposed junior level clinical immersion course will provide training and preparation of undergraduate engineering students through virtual reality clinical immersion experiences to be able to identify and evaluate real world healthcare problems in today’s evolving healthcare infrastructure. Through both online and in class learning modules, students will be able to work in multidisciplinary teams to develop a proposed innovative medical solution that can improve current practices of healthcare that were observed through virtual reality immersion. Using this scalable approach, large institutions and those institutions who do not have access to medical centers will be able to improve the next generation of biomedical engineering education by allowing students who would otherwise be unable to enter a clinic an understanding of current medical practices and how to identify and use technologies to improve the current field of healthcare.

PI_NAMEs: KHINE, MICHELLE ;KING, CHRISTINE E (contact);WIECHMANN, WARREN

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: Active Learning;Ambulatory Care;Biomedical Engineering;Caring;Clinic;Clinical;Clinics and Hospitals;Collaborations;commercialization;Communication;design;Development;E-learning;economic evaluation;Education;Educational Curriculum;Educational process of instructing;Engineering;engineering design;Environment;Ethics;Evaluation;experience;Film;Healthcare;ideation;Immersion;improved;Industry;Infrastructure;innovation;inpatient service;Institution;Interview;Intuition;invention;Learning;Learning Module;lectures;Life;Manikins;Marketing;Medical;Medical center;Medical Device;multidisciplinary;next generation;novel;open source;Operative Surgical Procedures;Pathway interactions;pedagogy;Persons;Physicians;Preparation;Problem Solving;Product Approvals;product development;programs;Protocols documentation;prototype;Rotation;simulation;skills;student training;Students;Teaching Method;Techniques;Technology;Training;undergraduate student;virtual;virtual reality;virtual reality environment;virtual reality simulation;web site;Work;working group;World Health

PROJECT_TITLE: Enhancing Biomedical Engineering Education Clinical Needs Finding Courses through Immersive and Virtual Experiences


ORG_CITY: BOSTON

ORG_DEPT: PHYSICS

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: Project Narrative The aim of this research proposal is to gain mechanistic understanding of the relationships among genomic variation, phenotype, and disease. The proposed research will combine data from DNA-DNA proximity ligation assays and multiple genome alignments to extract coevolutionary information about DNA elements and to infer the network of functional interactions among them. The PI has already made important contributions to the field of 3D genomics employing similar approaches.

PI_NAMEs: DI PIERRO, MICHELE  (contact)

PROGRAM_OFFICER_NAME: YU, GUOQIN

PROJECT_TERMS: 3-Dimensional;Affect;Architecture;Biological Assay;Biology;cell type;Chromosomes;Computing Methodologies;Coupling;Data;Data Set;Disease;Distal;DNA;Elements;experimental study;Explosion;Frequencies;functional genomics;Genetic Transcription;genetic variant;Genome;genomic data;genomic variation;Genomics;Health;Hi-C;Human;improved;insight;Life;Ligation;Link;Liquid substance;machine learning method;Maps;Measures;Methods;Modeling;Nature;organizational structure;Phase;Phenotype;Play;Research;Research Proposals;Resolution;Role;Trees;Untranslated RNA;Variant;variant of interest

PROJECT_TITLE: Coevolution and Functional Interactions in the Non-Coding Genome

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-S(55)R]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Social Determinants of Health

ORG_CITY: PITTSBURGH

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE This application requests support for the five-year continuation of our NIMH-funded institutional training grant, “A Training Program to Address HIV-related Health Disparities in MSM” seated within a leading School of Public Health, a research environment rich in HIV prevention research, LGBT health research, theoretical and empirical approaches to explaining risk among MSM, and HIV global health and bio-behavioral research, all creating an ideal environment to rain the next generation of HIV prevention scientists who will address the epidemic among MSM. This training program has been designed with the goal of providing trainees with the necessary skill sets to not only launch their careers, but also to make a substantial difference in the fight against HIV/AIDS among MSM. Continuation of a T32 training program within an extraordinarily rich environment will continue a mechanism to mentor the next generation of HIV prevention scientists who will be uniquely poised to find ways to end the epidemic among MSM.

PI_NAMEs: EGAN, JAMES ERIN;HAWK, MARY ELIZABETH (contact)

PROGRAM_OFFICER_NAME: KAMATH, SUSANNAH M A

PROJECT_TERMS: Address;health disparity;HIV;men who have sex with men;Training Programs


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

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE The aging process directly leads to a multitude of diseases that affect nearly all systems of the body, including blood system. We have discovered a candidate rejuvenation signaling pathway and we intend to test whether enhancing this signaling axis can restore the functional capacity of an aging blood system. These studies will lay the foundation for the development of therapeutic strategies to rejuvenate the aged blood stem cell and to reduce the morbidity and mortality associated with myelosuppression used to treat a wide range of age-related hematopoietic disorders.

PI_NAMEs: BUTLER, JASON MATHEW (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Activities of Daily Living;Affect;age related;aged;Aging;aging population;aging process;aging related;animal imaging;Animal Model;Award;Biological Assay;Blood;Blood Vessels;Body System;bone aging;Bone Marrow;bone preservation;Cell Maintenance;Cell Therapy;Cells;Clinical Trials;Data;Defect;design;Development;Disease;DNA Damage;Endothelial Cells;endothelial stem cell;Endothelium;experimental study;Failure;fitness;Foundations;functional restoration;Genes;healthspan;healthy aging;Hematopoiesis;Hematopoietic;hematopoietic stem cell expansion;hematopoietic stem cell niche;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Hematopoietic System;Imaging Techniques;improved;in vivo;in vivo Model;Infusion procedures;Injury;innovation;insight;Knockout Mice;Longevity;Mesenchymal Stem Cells;Molecular;Morbidity - disease rate;mortality;Myelosuppression;Natural regeneration;netrin receptor;new therapeutic target;novel;NTN1 gene;old mice;Organ;overexpression;Pathologic;Pathway interactions;permissiveness;Phenotype;Play;Predisposition;Premature aging syndrome;preservation;prevent;Publishing;receptor;Recovery;Regenerative Medicine;Regimen;Rejuvenation;repaired;Research;Research Proposals;Resolution;response;Risk;Role;Scientist;self-renewal;Signal Pathway;Signal Transduction;Source;stem cell function;stem cells;success;System;Testing;Therapeutic;therapeutic development;Tissues;Vascular System

PROJECT_TITLE: Preserving bone marrow niche integrity and function to rejuvenate aged hematopoietic stem cells

STUDY_SECTION: HTBT

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Immunization;Infectious Diseases;Orphan Drug;Pediatric;Prevention;Rare Diseases;Social Determinants of Health;Vaccine Related

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: NARRATIVE Relevance to public health There is a need to develop vaccines protective against Shigella spp, including in young children in resource-limited areas. We propose to advance a quadrivalent shigella conjugate vaccine to address this need.

PI_NAMEs: RYAN, EDWARD T. (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Acids;Address;Amines;Animal Model;Animals;Antibodies;Bacteria;Bangladesh;Biological Assay;Biomedical Engineering;Biotechnology;Carbohydrate Chemistry;Carrier Proteins;Cavia;Cessation of life;Chemicals;Chemistry;Child;Cholera;clinically relevant;Conjugate Vaccines;cost;Cyclic GMP;Data;Development;diarrheal disease;Enteral;Evaluation;experience;Formulation;Future;General Hospitals;Generations;Goals;guinea pig model;Human;Immune response;Immunity;Immunization;immunogenic;immunogenicity;Immunologics;Individual;Industry;industry involvement;International;international center;international partnership;intraperitoneal;Investments;Knowledge;Korea;Koreans;Link;Lipopolysaccharides;low and middle-income countries;Macaca;manufacture;Manufacturer;manufacturing run;Massachusetts;meetings;Modeling;Monoclonal Antibodies;Mus;nonhuman primate;O Antigens;Oligosaccharides;pathogen;Pharmacologic Substance;phase 1 testing;Polysaccharides;pre-clinical;preclinical evaluation;Preclinical Testing;Preparation;Primates;Procedures;Process;product development;Production;programs;protective efficacy;Protocols documentation;Public Health;Recording of previous events;Reproducibility;Research;Resource-limited setting;response;Serotyping;Shigella;Shigella flexneri;Shigella Infections;Shigella sonnei;Shigella Vaccines;Source;South Korea;Species Specificity;stability testing;T-Lymphocyte;technology platform;Technology Transfer;Tetanus Toxin;timeline;Typhoid Fever;United States National Institutes of Health;Universities;vaccine development;Vaccines;Vibrio cholerae;Virulent;Work

PROJECT_TITLE: Shigella Conjugate Vaccine (SCV4) Development, Characterization, and Pre-clinical Evaluation


NIH_SPENDING_CATS: Bioengineering;Neurosciences;Physical Injury - Accidents and Adverse Effects;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Narrative The current proposal is an innovative research plan to determine, for the first time, whether administration of antioxidant (NACA) or alternative biofuel (ALC) known to maintain mitochondrial bioenergetics and promote functional neuroprotection after contusion spinal cord injury (SCI), in combination with novel intrathecal injection of isolated muscle mitochondria embedded in a thermo-gelling, erodible hydrogel system to protect mitochondrial viability fosters greater neuroprotective efficacy. The use of an injectable hydrogel will permit the development of a local environment which can aide in maintaining mitochondrial health through optimization of the hydrogel niche. The knowledge gained from the proposed experiments will provide direct insight into the use of hydrogel systems for organelle delivery in vivo, and the potential of this novel combinatorial therapeutic intervention(s) to maintain cellular bioenergetics while reducing oxidative stress following SCI to promote tissue sparing and functional recovery.

PI_NAMEs: PATEL, SAMIRKUMAR  (contact)

PROJECT_TERMS: Acute;Antioxidants;Biochemical;Bioenergetics;Cell Count;cell injury;Cells;combinatorial;Confocal Microscopy;Cytosol;design;Development;dosage;Dose;Engineering;Environment;experimental study;extracellular;Fostering;Functional disorder;functional outcomes;Gel;Glutathione;Health;Histologic;Homeostasis;Hyaluronic Acid;Hydrogels;Hypersensitivity;improved;In Vitro;in vivo;in vivo evaluation;Inflammatory;Injectable;injured;Injury;innovation;insight;Intervention;Intrathecal Injections;Kinetics;Knowledge;Label;Levocarnitine Acetyl;Locomotion;Maintenance;Mechanics;Methylcellulose;Mitochondria;mitochondrial dysfunction;Molecular Chaperones;Muscle Mitochondria;N-Acetylcysteinamide;neuropathology;neuroprotection;novel;Organelles;Osmotic Pressure;Outcome Measure;Oxidative Stress;PC12 Cells;Pharmacologic Substance;Polymers;preservation;Production;Property;Proteins;Rattus;Recovery of Function;Reporting;Research;Route;Site;Soleus Muscle;Spinal Cord;Spinal Cord Contusions;Spinal cord injury;Spinal Injections;System;Testing;Therapeutic Intervention;Time;Tissues;Transplantation;uptake

PROJECT_TITLE: Enhanced Mitochondrial Viability via Engineered Hyrdogels for Intrathecal Spinal Cord Delivery

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Infectious Diseases;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Metastatic breast cancer is a deadly disease with no effective cure to date. This proposal aims to elucidate a novel function for nuclear cGAS in suppressing metastatic gene expression independent of its canonical function in innate immunity. We will also examine whether cGAS acetylation is a critical regulation to promote cGAS nuclear enrichment and whether inhibiting the major cGAS deacetylase could be used as a new avenue of therapeutic intervention for metastatic breast cancer.

PI_NAMEs: LIU, PENGDA  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: 3-Dimensional;Acetylation;Acetyltransferase;Amino Acid Motifs;ATAC-seq;Bacterial Infections;Binding;Biochemical;Biological;Biological Assay;Biophysics;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Patient;Cadherins;cancer recurrence;Cell Aging;cell motility;Cell Nucleus;cell type;Cessation of life;ChIP-seq;Chromatin;Chromatin Structure;Clinical;clinical prognosis;cohort;Complex;Cytoplasm;Data;Deacetylase;Deacetylation;Development;Disease;DNA;Enzymes;Epithelial Cells;epithelial to mesenchymal transition;Exhibits;Female;Gene Expression;Gene Silencing;Genes;Genetic;genetic approach;genetic regulatory protein;Genetic Transcription;genome-wide;Genomic DNA;Genomics;HDAC7 histone deacetylase;histone methylation;Histones;Human;Immune;Immune Evasion;Immune mediated destruction;immune resistance;Immune system;In Vitro;in vivo;Informatics;Injections;Innate Immune Response;insight;Knock-in;lymph nodes;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;Mammary Neoplasms;Mediating;Metastatic breast cancer;Metastatic to;migration;Mitochondrial DNA;Molecular;mortality;mouse model;mRNA Expression;Natural Immunity;Neoplasm Metastasis;novel;novel therapeutics;Nuclear;Nuclear Import;Nuclear Localization Signal;Outcome;pathogen;Pathway interactions;Peptides;Phenotype;Play;Post-Transcriptional Regulation;prevent;Primary Neoplasm;Prognostic Marker;Proteomics;Reader;Regulation;Role;Sampling;sensor;Signal Transduction;Specimen;Stimulator of Interferon Genes;Tail;Testing;The Cancer Genome Atlas;Therapeutic;therapeutic development;Therapeutic Intervention;therapeutically effective;Tissue Microarray;Tissues;transcriptome;transcriptome sequencing;tumor-immune system interactions;tumorigenesis;Veins;Viral;Virus Diseases;Woman;Xenograft procedure

PROJECT_TITLE: Elucidating novel functions of cGAS in breast cancer

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

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

ORG_CITY: BROOKLYN

ORG_NAME: SUNY DOWNSTATE MEDICAL CENTER

ORG_STATE: NY

PHR: NARRATIVE TRANSPORT II is aimed at expanding TRANSPORT I by enhancing the health equity research infrastructure at SUNY Downstate, recruiting and training more than 550 trainees and community partners, and developing multisectoral partnerships with key stakeholders.

PI_NAMEs: BOUTIN-FOSTER, CARLA ;LAMBERT, WILLIAM MARCUS (contact);RILEY, WAYNE JOSEPH;SALIFU, MORO O.

PROGRAM_OFFICER_NAME: MARSHALL, VANESSA J

PROJECT_TERMS: Academic Medical Centers;Acceleration;Advocacy;Advocate;Area;Award;behavioral and social science;Behavioral Sciences;Biomedical Research;Black race;Black, Indigenous, People of Color;career;career development;certificate program;Clinical Research;Communities;community academic partnership;community based participatory research;community engaged research;community engagement;Community Health;community partners;community science;design;Disparity;diversity and equity;doctoral student;Education;empowerment;Endowment;Enrollment;Environment;Equity;Faculty;Fostering;Funding;graduate student;Grant;Health;Health Disparities Research;health disparity;Health equity research;Health Occupations;Health Sciences;High School Student;Hispanic;implementation science;Income;Individual;Infrastructure;innovation;literacy;Marketing;Medically Underserved Area;Medicine;member;Mentors;Mentorship;Mission;Multiple Partners;National Heart, Lung, and Blood Institute;National Institute on Minority Health and Health Disparities;New York City;novel;Participant;Persons;Policies;Population;Population Sciences;post-doctoral training;Postdoctoral Fellow;pre-doctoral;Program Development;programs;Public Health;recruit;Research;research and development;Research Design;Research Infrastructure;Research Methodology;Research Personnel;Research Training;scale up;Scholars Program;Scholarship;Schools;Science;Scientist;senior faculty;Senior Scientist;skills;social determinants;Social Justice;Social Sciences;Structure;Students;success;summer program;Sustainable Development;symposium;Time;Training;Training and Infrastructure;Training Programs;Translating;translational applications;translational engagement;undergraduate student;Underrepresented Populations;United States Health Resources and Services Administration;Universities;Volatilization

PROJECT_TITLE: TRANSPORT II


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;Health Services;Neurodegenerative;Neurosciences;Palliative Care;Telehealth

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Family and unpaid caregivers are at the forefront of managing Alzheimer’s Disease and Related Dementias (ADRD) but are not well-supported in health care delivery. The actions of poorly informed and supported caregivers negatively affect persons living with ADRD and caregivers themselves. The challenges of ADRD caregiving may be alleviated with tailored services and supports. However, evidence-based models have typically been developed outside real-world care settings; few explicitly engage family at the point of care or are poised for widespread diffusion. The spread of consumer health information technology affords new opportunities to support ADRD caregivers within health care delivery. The patient portal allows patients to view test results and sections of their electronic medical record, perform health management tasks (e.g. scheduling visits, paying bills, filling prescriptions), access educational materials, and communicate with clinicians using secure messaging. Many care delivery organizations allow patients to share access to their patient portal account by registering a “care partner” to have their own identity credentials (login/password). Through shared access, patients may select whether and who electronically interacts with clinicians on their behalf, thus, respecting patient preferences while supporting care partners with timely information about patient health and treatments, and a mechanism to electronically navigate health system demands. Emerging evidence suggests that engaging care partners through shared access to the patient portal improves patient and family communication and confidence in their ability to manage care. Shared access may be particularly relevant in ADRD care due to the long and progressive course of the disease and heavy reliance on caregivers. Little is now known about electronic information sharing preferences and practices of persons with ADRD and their caregivers, or the feasibility of deploying novel interventions through consumer health information technologies to better support ADRD care and management. This application responds to RFA-AG-21-007 by building a program of health services research to address Alzheimer’s Disease and Related Dementias Implementation Milestone 13.I to support research on technology-based dementia assessment, care, and management. The applicant is an established investigator who is trained in health services research and gerontology, has deep expertise in the study of family caregiving, and a robust research portfolio that bridges population-based social science and applied behavioral interventions that are embedded in real world care delivery contexts. The program assembles a multidisciplinary team of new and existing mentees at varied career stages to increase evidence regarding the role and use of consumer health information technology in ADRD care and management, and novel technology-supported strategies that hold promise for ADRD assessment, care, and management.

PI_NAMEs: WOLFF, JENNIFER L. (contact)

PROGRAM_OFFICER_NAME: KIM, THERESA YOUNGJOO

PROJECT_TERMS: Address;Affect;Alzheimer's disease related dementia;Behavior Therapy;care delivery;career;Caregiver support;Caregivers;Caring;Communication;Computerized Medical Record;Credentialing;Dementia;dementia care;Dementia caregivers;dementia caregiving;Diffusion;Disease;education access;Educational Materials;Electronics;evidence base;Family;family caregiving;Family Study;Gerontology;Health;health care delivery;health information technology;health management;Health Services Research;Health system;improved;Intervention;Managed Care;Modeling;multidisciplinary;new technology;novel;patient portal;Patient Preferences;Patients;Persons;point of care;population based;preference;programs;provider communication;Research;Research Personnel;Research Support;Role;Schedule;Secure;Services;Social Sciences;Technology;Test Result;Training;Visit

PROJECT_TITLE: Consumer Health Information Technology to Engage and Support  ADRD Caregivers: Research Program to Address ADRD Implementation MIlestone 13.I


ORG_CITY: CHICAGO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative  Physical exercise exerts beneficial effects against type 2 diabetes (T2D), but the mechanisms by which exercise induces systemic metabolic benefits are unclear. We recently discovered that activation of autophagy, a lysosomal degradation pathway, in non-contractile tissues during exercise, via exercise-stimulated muscle-secreted fibronectin (Fn1) and downstream pathways, may play an important role in the regulation of exercise-induced insulin sensitization. In this proposal, we will demonstrate the role and mechanism of autophagy activation in non-contractile tissues in driving exercise-induced metabolic benefits against T2D.

PI_NAMEs: HE, CONGCONG  (contact)

PROGRAM_OFFICER_NAME: WANG, XUJING

PROJECT_TERMS: Acute;Address;Affect;Anti-diabetic Drugs;Automobile Driving;Autophagocytosis;Autophagosome;Binding;Biochemical;Biological;Biology;Cells;Cellular biology;Circulation;Communication;Complex;Contracts;Cultured Cells;Data;Degradation Pathway;Disease;Exercise;Extracellular Matrix Proteins;Fasting;feeding;Fibronectin Receptors;Fibronectins;Genetic;glucose metabolism;glucose tolerance;Glycoproteins;High Fat Diet;Impairment;improved;Insulin;Integrin alpha5beta1;Integrin Signaling Pathway;Integrins;knock-down;Knock-in;Knock-in Mouse;Liver;Lysosomes;MAPK8 gene;Mediating;Metabolic;Metabolism;Modeling;mouse model;Mus;Muscle;Muscle Cells;Muscle Contraction;Muscle Fibers;mutant;Myoblasts;Non-Insulin-Dependent Diabetes Mellitus;Pathway interactions;Physical Exercise;Physiological;PIK3CG gene;Play;prevent;Prevention;Proteins;Proteomics;receptor;Recycling;Regulation;Rest;Risk Factors;Role;Serum;Signal Pathway;Signaling Molecule;Skeletal Muscle;Stress;stressor;Structure;therapeutic development;Therapeutic Intervention;Tissues;tumorigenesis;Undifferentiated;Wild Type Mouse

PROJECT_TITLE: Mechanism of autophagy activation in exercise-induced anti-diabetic benefits

STUDY_SECTION: POMD

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


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Breastfeeding, Lactation and Breast Milk;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Complementary and Integrative Health;Depression;Dissemination and Implementation Research;Health Services;Major Depressive Disorder;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Pediatric;Pregnancy;Prevention;Serious Mental Illness;Telehealth;Women's Health Research

ORG_CITY: WORCESTER

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Narrative This application is aimed at development and preliminary testing of a text messaging intervention that will reduce the risk of a major depressive episode and worsening depressive symptoms in perinatal individuals. The system would screen pregnant individuals, send tailored text messages with links to enhanced content, and would include a peer chat function. This accessible text platform would leverage both the ease of use inherent in text messages and the power of enhanced content drawn evidence from based behavioral interventions (Interpersonal Therapy and Cognitive Behavioral Therapy).

PI_NAMEs: YONKERS, KIMBERLY A (contact)

PROJECT_TERMS: Adverse effects;Behavior Therapy;Breast Feeding;Caregivers;Caring;Cellular Phone;Child;Child Rearing;Cognitive Therapy;Communication;Complement;cost;Counseling;COVID-19 pandemic;dashboard;Data;depression prevention;depressive symptoms;Development;Education;Effectiveness;Elements;evidence base;Exercise;experience;Explosion;Health;health care settings;Health Personnel;Healthcare;Impairment;implementation intervention;implementation outcomes;improved;Individual;Infant Development;interpersonal therapy;Intervention;inventory of depressive symptomatology;Link;Literature;Lived experience;Medical;Mental Depression;Mental Health Services;Minority Groups;mobile phone based intervention;Modeling;mood symptom;Mothers;Motivation;Nature;Participant;Paste substance;Patient Self-Report;Patients;peer;peer support;Perinatal;peripartum depression;Persons;Postpartum Depression;pragmatic implementation;Pregnancy;pregnant;Premature Birth;prevent;Prevention;Prevention program;preventive intervention;Process;Professional counselor;programs;Provider;Randomized;randomized trial;randomized, clinical trials;Reporting;Reproductive Health;Research;Research Domain Criteria;Risk;Risk Reduction;Screening procedure;Secure;Self Efficacy;single episode major depressive disorder;Site;Sleep Disorders;social stigma;standard care;Stressful Event;System;tailored text messaging;Technology;Testing;Text;Text Messaging;text messaging intervention;Therapeutic Intervention;Time;Training;Triage;United States Preventative Services Task Force;usability;user centered design;user-friendly;web app

PROJECT_TITLE: Development of a Text Intervention for Perinatal Depression


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Depression;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Pediatric;Pregnancy;Prevention;Serious Mental Illness;Social Determinants of Health;Women's Health Research

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Current approaches to prevention and treatment of depression and anxiety among pregnant and postpartum individuals often operate within larger health systems that 1) lack mental health providers, and 2) are not trustworthy for birthing people, especially those who are from communities that have been marginalized. Scalable interventions that focus on improving perinatal mental health care for communities that have been marginalized are needed. We will develop and test an approach to linking the health system and the community to improve the reach and impact mental health care for pregnant and postpartum individuals with a particular focus on communities that have been marginalized.

PI_NAMEs: LARSON, ELYSIA  (contact)

PROGRAM_OFFICER_NAME: SWEENEY, MARY MARGARET

PROJECT_TERMS: acceptability and feasibility;Address;Adoption;Affect;Anxiety;Anxiety Disorders;barrier to care;Behavioral;Birth;Black Populations;career;Caring;Child Psychiatry;Child Rearing;Client;Communities;community based participatory research;community engaged research;community partners;Consult;Consultations;Coping Skills;COVID-19 pandemic;Data;Data Collection;Dedications;Development;Education;effective intervention;Effectiveness;Emotional;Ensure;Equity;Evidence based intervention;experience;feasibility trial;Fostering;Foundations;Goals;Health Personnel;Health system;healthcare community;implementation science;improved;Individual;Infection;innovation;Intervention;intervention refinement;Lead;Leadership;Link;Manuals;marginalization;marginalized community;Massachusetts;Measures;Mental Depression;Mental Health;Mental Health Services;Mentored Research Scientist Development Award;Mentorship;Methods;Modeling;Modification;Mood Disorders;Moods;Morbidity - disease rate;Mothers;multi-component intervention;National Institute of Mental Health;Obstetrical Nursing;Outcome;overdose death;Patients;Perinatal;Perinatal Care;perinatal health;perinatal mental health;perinatal period;peripartum depression;Persons;pilot test;Population;Positioning Attribute;Postpartum Period;Pregnancy Complications;pregnancy related death;pregnant;prevent;Prevention approach;preventive intervention;programs;Provider;Psychiatrist;psychosocial;Qualitative Methods;racism;Randomized;recruit;reduce symptoms;Reporting;Research;Research Methodology;Resources;response;Schedule;Service delivery model;Site;skills;social stigma;Specialist;standard of care;Stress;success;Suicide;Symptoms;Techniques;Telephone;Testing;therapy development;tool;Training;uptake;Voice;Wait Time;women of color;Work

PROJECT_TITLE: Developing and testing a multi-component intervention to improve Perinatal Mental Health

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Public Health Relevance Statement VEXAS syndrome is a newly discovered, deadly autoinflammatory disease and currently has no cure. This proposal will test the therapeutic potential of auranofin for this deadly disease, based on our new finding that auranofin can correct the functional defect of the VEXAS syndrome-causing protein UBA1. Auranofin is a clinical drug currently used to treat rheumatoid arthritis, and therefore, this proposed study may pave the way for repurposing of auranofin as the first drug for treating VEXAS syndrome

PI_NAMEs: FANG, SHENGYUN  (contact)

PROGRAM_OFFICER_NAME: PARK, HEIYOUNG

PROJECT_TERMS: Acceleration;Adult;attenuation;Auranofin;autoinflammatory diseases;Binding;Biochemical;Bioinformatics;biological adaptation to stress;Biological Assay;Cell Line;Cell model;cell type;Cells;Cellular biology;Charge;Clinical;Co-Immunoprecipitations;Codon Nucleotides;CRISPR/Cas technology;Cryoelectron Microscopy;cytokine;Data;Defect;Disease;Dose;effective therapy;Endoplasmic Reticulum;endoplasmic reticulum stress;Enhancers;Enzymes;Exhibits;Gene Expression;Genes;Goals;Hematopoietic stem cells;Immune;In Vitro;in vitro testing;Inflammation;Inflammatory;Inflammatory Response;Innate Immune Response;Interferon Type II;Interferons;Interleukin-6;Investigation;life span;Link;Mass Spectrum Analysis;Mediating;misfolded protein;Missense Mutation;Modeling;Molecular Conformation;monocyte;mutant;Mutation;Myelogenous;Myeloid Cells;Natural Immunity;neutrophil;NF-kappa B;novel;Pathway interactions;Patients;peripheral blood;Pharmaceutical Preparations;pharmacologic;Process;protein expression;Protein Secretion;Proteins;Proteome;Proteomics;proteostasis;public health relevance;Quantitative Reverse Transcriptase PCR;Recommendation;reconstitution;Refractory;Reporting;response;Rheumatoid Arthritis;Serum;Signal Transduction;Spectrometry;Stress;Syndrome;Testing;Text;Therapeutic;Therapeutic Effect;therapeutic evaluation;TNF gene;treatment strategy;Ubiquitin;Ubiquitin-Conjugating Enzymes;ubiquitin-protein ligase;Ubiquitination;United States National Institutes of Health;Zebrafish

PROJECT_TITLE: Pharmacologic enhancement of UBA1 activity in models of VEXAS syndrome

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


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

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Tumor associated macrophages (TAMs) are highly suppressive in the tumor microenvironment (TME) and contribute to chemo- and immuno-therapy resistance. Our lab has made the discovery that a commonly used cancer therapy, PARP inhibitors (PARPi), induce lipogenic metabolism in TAMs rendering them even more suppressive, in which they inhibit T-cell function and activation, and limit therapeutic responses; importantly, however, in the absence of TAMs, PARPi promotes metabolically superior T-cell antitumor traits. Our proposal will formally determine how lipogenic TAM and T-cell metabolism is regulated during PARPi therapy, which is likely to provide opportunities for the development of novel treatment strategies that hold the power to overcome the immune-suppressive TME and improve PARPi therapy success in a number of cancer types.

PI_NAMEs: GUERRIERO, JENNIFER L. (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: adaptive immunity;angiogenesis;Antineoplastic Agents;Antitumor Response;Bioenergetics;Breast Cancer Patient;Breast Cancer Treatment;Breast Oncology;Cancer Patient;cancer therapy;cancer type;CD8-Positive T-Lymphocytes;Cell Physiology;Cell Survival;Cells;Cellular biology;cellular imaging;Cellular Metabolic Process;chemotherapy;Clinical;clinical translation;Clinical Trials;Combined Modality Therapy;Cytotoxic T-Lymphocytes;Data;Dependence;design;Development;DNA Damage;early phase clinical trial;early phase trial;Effectiveness;Equipoise;Excision;Exhibits;fitness;Goals;Human;Immune;immune checkpoint blockade;Immunotherapy;improved;In Vitro;in vivo;inhibitor therapy;Knowledge;Lead;lipid biosynthesis;lipidomics;Lipids;Macrophage;Malignant Breast Neoplasm;Mammary Neoplasms;Mediating;Metabolic;metabolic fitness;Metabolism;metabolomics;monocyte;mouse model;Mus;Neoplasm Metastasis;next generation;novel;novel therapeutic intervention;Nutrient;optimal treatments;Outcome;Oxygen;PARP inhibition;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Poly(ADP-ribose) Polymerase Inhibitor;Positioning Attribute;programs;Protein Biosynthesis;Proteomics;recruit;Regulation;Research;Resistance;response;Sampling;Solid Neoplasm;SRE-1 binding protein;success;synergism;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;therapy resistant;Tissues;trait;Translations;Treatment Efficacy;treatment response;treatment strategy;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor microenvironment;Tumor-associated macrophages;tumorigenesis;Work

PROJECT_TITLE: Immunometabolic pathways enabled by PARP inhibition in breast cancer

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]