NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics;Hematology;Human Genome;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE Myelodysplastic syndromes (MDS) refers to a collection of clonal blood disorders characterized by ineffective production of mature blood cells by the hematopoietic stem cells in the bone marrow. Various genetic mutations, including those that participate in RNA processing, can corrupt the ability of bone marrow stem cells produce functional blood cells. In this proposal, we seek to understand the molecular causes and consequences of genomic instability caused by RNA splicing factor mutations, and to identify novel treatment options for MDS patients.

PI_NAMEs: LEE, STANLEY CHUN-WEI (contact)

PROGRAM_OFFICER_NAME: GREENBERG, WILLIAM A

PROJECT_TERMS: Affect;age group;age related;alpha-Thalassemia;Anemia;Blood Cells;Bone Marrow;Bone Marrow Stem Cell;BRCA mutations;Cell Line;Cells;CHEK1 gene;Clinical;Clinical Management;clinical translation;Clustered Regularly Interspaced Short Palindromic Repeats;Collection;Combined Modality Therapy;comorbidity;CRISPR interference;CRISPR screen;curative treatments;Custom;cytopenia;Data;Dependence;Development;Diagnosis;Disease;DNA;DNA Damage;DNA Repair;DNA Sequence Alteration;druggable target;Dysmyelopoietic Syndromes;Dysplasia;Elderly;experimental study;Failure;FDA approved;functional decline;Gene Expression Regulation;Gene Mutation;Genes;Genetic;Genetic Engineering;Genetic Transcription;genome integrity;Genome Stability;Genomic Instability;Germ Lines;Hematological Disease;Hematopoietic;Hematopoietic stem cells;high risk;Homeostasis;homologous recombination;Human;Hybrids;improved outcome;in vivo;Induced Mutation;Inferior;inhibitor;Left;Libraries;Marrow;Mediating;Mediator;Messenger RNA;Modeling;Molecular;Molecular Abnormality;Molecular Genetics;Morphology;mRNA Precursor;Mus;mutant;Mutate;Mutation;novel;novel therapeutics;Pathogenesis;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;Poly(ADP-ribose) Polymerase Inhibitor;pre-clinical;Pre-Clinical Model;predictive marker;Process;Production;Prognosis;Proteins;recombinational repair;replication stress;Resolution;response;RNA;RNA Processing;RNA Splicing;Sampling;screening;Secondary to;Series;Signal Transduction;Single-Stranded DNA;Site;Solid Neoplasm;Somatic Mutation;Spliceosomes;SRSF2 gene;Stem cell transplant;stem cells;Structure;synergism;synthetic lethal interaction;Testing;Therapeutic;therapeutic evaluation;therapeutic target;therapeutically effective;Transplantation;treatment strategy;United States;Validation

PROJECT_TITLE: Causes and consequences of genomic instability in myelodysplasia

STUDY_SECTION: MCTC

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics C Study Section [MCTC]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Diabetes;Endocrine Disruptors;Kidney Disease;Pediatric;Prevention

ORG_CITY: Los Angeles

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: PROJECT NARRATIVE Diabetic kidney disease (DKD) in youth with type 2 diabetes (T2D) dramatically increases the risk of early kidney failure and mortality and is increasing in prevalence, but preventive therapies are limited. Exposure to per- and polyfluoroalkyl substances (PFAS) may increase DKD risk in youth with T2D and is associated with altered renal organic anion transporters, which actively reabsorb PFAS from urine, concentrate PFAS in proximal tubules, and potentially increasing PFAS nephrotoxicity and risk of DKD. In this first-of-its-kind study, we will leverage two longitudinal cohorts of youth with T2D to examine how organic anion transporters and exposure to PFAS affect DKD risk in youth and identify potential therapeutic targets and prevention approaches for mitigating PFAS associated nephrotoxicity in high-risk populations.

PI_NAMEs: GOODRICH, JESSE ALLEN (contact)

PROGRAM_OFFICER_NAME: MENDLEY, SUSAN RUTH

PROJECT_TERMS: absorption;Accounting;Address;Adolescence;Adolescent;Affect;African American;Albuminuria;Animals;Biological;Biological Markers;Blood;Cells;Cessation of life;Chemicals;Clinical;cohort;Colorado;consumer product;Data;data integration;Diabetic Nephropathy;Dialysis procedure;disorder prevention;disorder risk;ethnic minority;Ethnic Origin;Etiology;Exposure to;Factor Analysis;Filtration;follow-up;Funding;Gene Expression;Glomerular Filtration Rate;Glucose;Half-Life;hemodynamics;Heterogeneity;high risk population;Human;Hyperglycemia;Impairment;Individual;Industrial Product;inhibitor;inhibitor therapy;Injury;Injury to Kidney;innovation;Insulin Resistance;Intervention;Kidney;kidney biopsy;Kidney Failure;Latinx;Link;Longitudinal cohort;marginalized community;Measures;Mediating;Mediation;Methods;modifiable risk;mortality;multi-ethnic;multiple omics;National Institute of Diabetes and Digestive and Kidney Diseases;nephrotoxicity;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Organic Anion Transporters;Outcome;Persons;pharmacokinetic model;Phenotype;Pilot Projects;Plasma;Poison;Poly-fluoroalkyl substances;Predisposition;Prevalence;prevent;Prevention approach;Preventive therapy;prospective;Race;Regulation;Renal function;Risk;Risk Factors;risk mitigation;Serum;single-cell RNA sequencing;Sodium;Specific qualifier value;standard measure;Survival Analysis;symporter;Techniques;Testing;Therapeutic Intervention;therapeutic target;Time;time use;Toxic effect;transcriptomics;Tubular formation;United States National Institutes of Health;Urine;Visit;Youth

PROJECT_TITLE: PFAS Exposure and Diabetic Kidney Disease in Youth with Type 2 Diabetes: A Multi-Omic Approach for Prevention and Treatment

STUDY_SECTION: KEDD

STUDY_SECTION_NAME: Kidney Endocrine and Digestive Disorders Study Section[KEDD]


ADMINISTERING_IC: GM

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: ALBUQUERQUE

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: Narrative The New Mexico Academic Science Education and Research Training K12 IRACDA Program prepares postdoctoral fellows to excel in all facets of academic life at institutions likely to have highly diverse student populations. Training is achieved through: (1) conduct of cutting-edge research with scientists at the University of New Mexico, (2) career development and skill-building activities, and (3) practical teaching experiences at one of three partnered Minority Serving Institutions in New Mexico. Ninety-eight percent of ASERT alumni are in biomedical research or education positions, where they make new discoveries and technological advances, improve healthcare, innovate teaching strategies, and motivate the next generation of students in research.

PI_NAMEs: HARTLEY, REBECCA S.;LIDKE, DIANE  (contact)

PROGRAM_OFFICER_NAME: NELSON, SHAKIRA M

PROJECT_TERMS: Accreditation;Agreement;American Indians;Anthropology;Area;Bachelor's Degree;Biological;Biology;Biomedical Engineering;career;Career Mobility;Chemistry;cohort;college;Computational Science;Degree program;Development;Development Plans;Discipline;Diverse Workforce;Education;Educational process of instructing;Educational workshop;Engineering;Environmental Science;Equity;Evaluation;experience;Faculty;faculty mentor;Fellowship Program;Goals;Graduate Degree;Grant;Growth;Health Sciences;Hispanic;Individual;Institution;Interdisciplinary Study;Justice;K-Series Research Career Programs;Knowledge;Lead;Learning;Low income;Mathematics;meetings;member;Mentors;Minority;Minority-Serving Institution;New Mexico;Outcome Assessment;Pathway interactions;pedagogy;Pharmacologic Substance;physical science;Postdoctoral Fellow;Private Sector;Productivity;Program Evaluation;recruit;Research;research and development;Research Training;role model;Science;science education;Series;skills;Social Sciences;Southwestern Indian Polytechnic Institute;Students;Technology;Training;Training and Education;training opportunity;Training Programs;tribal college;undergraduate student;Universities;Work

STUDY_SECTION: TWD

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


ADMINISTERING_IC: CA

ED_INST_TYPE: HOSPITALS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Immunotherapy;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: HOUSTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: As a clinical scientist, I have led (as overall Principal Investigator) first-in-kind NCI-supported clinical trials evaluating circulating tumor DNA (ctDNA) as a predictive biomarker for adjuvant chemotherapy in patients with early-stage colon cancer as well as trials testing novel immunotherapy combinations for patients with incurable gastrointestinal malignancies. My research interest focuses on use of the liquid biopsy to characterize genomic (ctDNA) and transcriptomic (extravesicle RNA) changes in association with treatment responses, using plasma samples that may overcome historical challenges of obtaining paired tumor biopsy samples from clinical trials. In seeking R50 funding, I propose to apply these learned experiences to develop other NCI-led clinical trials for colorectal cancer and anal cancer that, if successful, would validate the use of the liquid biopsy as tool valuable for the design of clinical trials aimed to eradicate minimal residual disease (as informed by a “ctDNA(+) status”) and improve survival outcomes for patients with gastrointestinal malignancies.

PI_NAMEs: MORRIS, VAN K (contact)

PROGRAM_OFFICER_NAME: MAHER, MOLLY ELIZABETH

PROJECT_TERMS: Address;Adjuvant Chemotherapy;Biological Assay;Biological Markers;Biopsy Specimen;Blood;blood-based biomarker;Cancer Center;Cetuximab;Clinical;Clinical Trials;Clinical Trials Design;Colon Carcinoma;Colorectal Cancer;Combination immunotherapy;design;Detection of Minimal Residual Disease;Early Therapeutic-Clinical Trials Network;Enrollment;experience;Funding;Future;Genomics;Goals;Grant;Guidelines;hands-on learning;Head;health disparity;Immunotherapy;immunotherapy trials;improved;insight;Institution;interest;Lead;Leadership;liquid biopsy;Malignant neoplasm of anus;Malignant neoplasm of gastrointestinal tract;metastatic colorectal;Methodology;Microsatellite Repeats;Minority Enrollment;multiple omics;National Comprehensive Cancer Network;Nivolumab;novel;Outcome;participant enrollment;Patient-Focused Outcomes;Patients;phase II trial;Phase II/III Trial;pilot trial;Plasma;predictive marker;Principal Investigator;Randomized;Recommendation;Research;Residual Neoplasm;response;RNA;RNA analysis;Role;Sampling;Scientist;Site;Solid Neoplasm;Southwest Oncology Group;survival outcome;Techniques;Testing;therapeutically effective;tool;transcriptomics;translational study;treatment response;tumor;tumor DNA;Underrepresented Minority;Writing

PROJECT_TITLE: Multi-omic liquid biopsy assessment in NCI trials: evaluating ctDNA, extravesicle RNA, and outcomes with immunotherapy in patient with colorectal and anal cancers

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-1 (M1)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;Infectious Diseases;Lung

ORG_CITY: DALLAS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative The nasal mucosa serves as the initial site of viral exposure and infection but the mechanism by which viruses penetrate this physical barrier and infect cells remains unclear. We propose that respiratory viruses hijack motile cilia for viral entry into the nasal cavity. This work will define mechanisms by which respiratory viruses enter the nasal mucosa.

PI_NAMEs: WU, CHIEN-TING  (contact)

PROGRAM_OFFICER_NAME: KIM, SONNIE

PROJECT_TERMS: 2019-nCoV;ACE2;Air;airway epithelium;Anatomy;Architecture;base;Binding;Biological Models;Cell Culture Techniques;Cell fusion;Cell membrane;Cells;cellular microvillus;chemokine receptor;Cilia;cilium motility;comparative;CX3C Chemokines;Data;Defense Mechanisms;Distal;Epithelial Cells;Goals;Human;in vivo Model;Infection;inhibitor;insight;Invaded;Kinetics;Knowledge;Light;Link;Liquid substance;Mediating;Membrane;Membrane Fusion;Microscopy;Modeling;Mucins;Mucociliary Clearance;Mucous body substance;Nasal cavity;Nasal Epithelium;Nose;Organelles;particle;Penetration;Property;protein transport;Publishing;receptor;Replication-Associated Process;Research;Respiration;respiratory;respiratory infection virus;Respiratory syncytial virus;Respiratory Syncytial Virus Infections;Respiratory syncytial virus RSV proteins;respiratory virus;Role;SARS coronavirus;SARS-CoV-2 infection;Site;Specialized Epithelial Cell;Structure of mucous membrane of nose;superresolution microscopy;Surface;System;Time;Tissues;trafficking;Travel;Viral;viral RNA;Virion;Virus;Virus Diseases;Virus Receptors;Work

PROJECT_TITLE: Cilia-mediated mechanisms of viral entry into nasal mucosa

STUDY_SECTION: VDT

STUDY_SECTION_NAME: Viral Dynamics and Transmission Study Section [VDT]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Networking and Information Technology R&D (NITRD);Radiation Oncology;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative  Brachytherapy is a procedure to radiate a tumor internally through thin tubes called catheters inserted in the tissue and has been widely used to treat locally advanced cervical and endometrial cancers. For safe and complete radiation, placing the catheters in the tumor at optimal locations is crucial. In this project, we will develop a remotely-controlled manipulator that assists the clinician in placing the catheters in the patient in an imaging scanner while checking their locations using advanced shape-sensing technology and providing real-time quantitative evaluation of the implant quality during the implant procedure for better clinical outcomes.

PI_NAMEs: CORMACK, ROBERT A.;IORDACHITA, IULIAN IOAN;TOKUDA, JUNICHI  (contact)

PROGRAM_OFFICER_NAME: BITTMANN, MORIA FISHER

PROJECT_TERMS: Anatomy;Brachytherapy;Catheters;Cessation of life;Clinical;Clinical Data;clinical translation;Collaborations;Compensation;Computer software;Computers;Dose;dosimetry;Endometrial Carcinoma;Evaluation;experimental study;falls;Feedback;Fiber;Fiber Optics;Goals;Gynecologic Brachytherapy;High-Dose Rate Brachytherapy;Image;image guided;Image-Guided Surgery;Implant;implantation;Implantation procedure;improved;Locally Advanced Malignant Neoplasm;Location;machine learning model;Magnetic Resonance;Magnetic Resonance Imaging;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of cervix uteri;Malignant Neoplasms;Measurement;Measures;Modeling;multidisciplinary;novel;Oncology;optical fiber;Organ;Outcome;Patient imaging;Patients;Positioning Attribute;Postoperative Period;Procedures;Process;prostate biopsy;Quantitative Evaluations;Radiation;Radiation Dose Unit;Radioactive;Recording of previous events;Risk;robot assistance;Robotics;Scientist;sensor technology;Shapes;Source;standard of care;Structure;System;Technology;teleoperation;Testing;Thinness;Three-Dimensional Imaging;Time;Tissues;Toxic effect;training data;treatment planning;Tube;tumor;Tumor Volume;ultrasound;United States;Visualization;X-Ray Computed Tomography

PROJECT_TITLE: Robot-assisted catheter placement with novel shape-sensing stylet to facilitate adaptive image guided pelvic brachytherapy

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: Our application aims to apply advances in tissue engineering to address the need for the development of cancer metastasis model that can reflect in vivo biology. We aim to engineer a novel cancer metastasis model that can reflect organ-specificity and validate this model using kidney cancer. Success of this application will provide a powerful new tool for cancer research and reveal new cancer biology.

PI_NAMEs: WANG, ANDREW ZHUANG (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: Address;Adrenal Glands;anti-cancer research;Biological Models;Biology;Biomimetics;Bone Marrow;Brain;Cancer Biology;cancer care;Cancer cell line;Cancer Model;cancer site;cancer therapy;Cell Proliferation;Cells;Cultured Tumor Cells;Data;Development;disease model;Disseminated Malignant Neoplasm;Engineering;Event;Extracellular Matrix;Extracellular Matrix Proteins;Extracellular Protein;Fatty acid glycerol esters;Goals;Heart;Human;improved;In Vitro;in vivo;innovation;Kidney;Liver;Lung;lymph nodes;Malignant Neoplasms;Modeling;Morbidity - disease rate;mortality;Neoplasm Circulating Cells;Neoplasm Metastasis;neoplastic cell;novel;Organ;Organ Specificity;Pancreas;Patients;Pattern;personalized medicine;precision oncology;prevent;Process;Proliferating;Proteins;Renal Carcinoma;Reporting;Research;Rodent;screening;Site;Skeletal Muscle;Skin;Soil;Spleen;success;System;Technology;theories;Therapeutic;Tissue Engineering;Tissues;tool;treatment response;tumor;Tumor Biology;tumor microenvironment;tumor specificity;validation studies;Work

PROJECT_TITLE: Tissue engineered organ-specific cancer metastasis model for cancer research

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Services;Heart Disease;Hematology;Patient Safety;Stroke

ORG_NAME: HEBREW REHABILITATION CENTER FOR AGED

PHR: PROJECT NARRATIVE Half of adults aged 65 years or older with atrial fibrillation (AF) are not treated with oral anticoagulants (OAC) due to concerns for major bleeding. Even though the greatest need for left atrial appendage occlusion (LAAO) is in OAC-ineligible patients and patients with frailty, the randomized clinical trials of LAAO tested LAAO in OAC-eligible patients, did not measure frailty at baseline, and most likely excluded patients with frailty. The objective of the proposal is to address the evidence-practice gap by investigating utilization and the comparative effectiveness and safety of LAAO against therapeutic alternatives (i.e., OAC and non-use of OAC) and heterogeneous treatment effects by frailty status in medically complex routine population.

PI_NAMEs: KO, DARAE  (contact)

PROGRAM_OFFICER_NAME: SIDDIQUI, AYESHA SAEED

PROJECT_TERMS: Address;Adult;Affect;Anemia;Anticoagulants;Atrial Fibrillation;auricular appendage;Blood Platelets;Boston;Calendar;Cardiovascular system;Cessation of life;Characteristics;Chronic Kidney Failure;Clinical;Clinical Research;Clinical Trials;comorbidity;comparative effectiveness;comparative effectiveness study;comparative safety;Complex;Data;data registry;Data Set;Data Sources;Dementia;demographics;Devices;Effectiveness;effectiveness evaluation;effectiveness outcome;Elderly;Electronic Health Record;Eligibility Determination;Embolism;Event;evidence base;Exclusion;experience;fall injury;falls;Fee-for-Service Plans;frailty;Future;Goals;Guidelines;health care service utilization;Hemorrhage;Heterogeneity;high risk;Home;human old age (65+);improved;indexing;Individual;innovation;Ischemic Stroke;Israel;Left;Link;Massachusetts;Measures;Medical;Medical center;Medicare;Methods;older adult;Oral;Outcome;Outcome Measure;Outcomes Research;Patient-Centered Care;Patient-Focused Outcomes;Patients;Persons;Pharmaceutical Preparations;Pharmacoepidemiology;Pharmacotherapy;Population;Population Heterogeneity;Practice Guidelines;programs;Prophylactic treatment;Qualifying;randomized, clinical trials;Randomized, Controlled Trials;Recommendation;Recurrence;Research;Research Personnel;Risk;Safety;safety outcomes;safety study;Sampling;Site;Source;Stroke;Stroke prevention;Testing;Therapeutic;Time;Time trend;treatment effect;United States Centers for Medicare and Medicaid Services;Vulnerable Populations

PROJECT_TITLE: Utilization and Clinical Outcomes of Left Atrial Appendage Occlusion in Older Adults with Atrial Fibrillation and Frailty

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Infectious Diseases

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: The Infectious Disease and Basic Microbiological Mechanisms training program continues to train postdoctoral trainees as independent physician scientists (M.D. and M.D.-Ph.D.) and Ph.D. scientists able to recognize and answer clinically relevant questions in the fields of infectious diseases and microbiology. This training program is especially important now, as we witness the emergence of new infectious diseases and global pandemics, the continued challenges of illnesses due to antibiotic-resistant pathogens, and the development of revolutionary scientific technologies and approaches that have the potential to address these and other issues in the field.

PI_NAMEs: GOLDBERG, MARCIA B (contact)

PROGRAM_OFFICER_NAME: BROWN, LILIANA L

PROJECT_TERMS: Biological;Communicable Diseases

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Research Study Section[MID]


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

ORG_CITY: ANN ARBOR

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative. The metastatic niche is a site that promotes the homing and colonization of immune cells and cancer cells to solid organs, which is often the cause of mortality. We propose to develop nanoparticles the reprogram the function of innate immune cells to disrupt the metastatic niche and thereby enable the immune system to clear metastatic cancer cells from endogenous metastatic sites.

PI_NAMEs: JERUSS, JACQUELINE SARA;SHEA, LONNIE D (contact)

PROGRAM_OFFICER_NAME: CHEN, JERMONT

PROJECT_TERMS: 4T1;adaptive immune response;Adjuvant;Adjuvant Therapy;Adoptive Transfer;Behavior;Biodistribution;Blood;Breast Cancer Model;cancer cell;Cell Communication;Cell Count;cell type;Cells;Chemicals;chemokine;chimeric antigen receptor T cells;Circulation;Clinic;Clinical Trials;Complement;Cytoprotection;design;Development;Disease;Disseminated Malignant Neoplasm;Distal;Engineering;Environment;Goals;Growth;Homing;Immune;immune checkpoint blockade;Immune mediated destruction;Immune response;Immune system;Immunologist;immunomodulatory strategy;Immunosuppression;Immunotherapy;In complete remission;in vivo;Inflammatory;innate immune function;Innate Immune System;Intravenous;Lung;Malignant Breast Neoplasm;Malignant Neoplasms;Metastatic Neoplasm to the Lung;monocyte;mortality;Mus;Myelogenous;Myeloid Cells;nanoparticle;nanoparticle delivery;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;neutrophil;novel strategies;Organ;particle;Pathologic;Patients;Phase;Phenotype;polarized cell;Population;prevent;Primary Neoplasm;programs;Proliferating;Property;Recording of previous events;recruit;Recurrence;Research;Role;Safety;Site;Solid;Systemic disease;systemic inflammatory response;T cell response;T-Cell Activation;T-Cell Depletion;T-Lymphocyte;T-Lymphocyte Subsets;targeted treatment;Therapeutic;trafficking;Translating;Travel;Treatment Efficacy;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor progression;Tumor-infiltrating immune cells;Work

PROJECT_TITLE: Nanoparticles to reprogram innate immune cells and disrupt the metastatic niche

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


NIH_SPENDING_CATS: Clinical Research;Cystic Fibrosis;Lung;Pediatric;Rare Diseases

ORG_CITY: LEBANON

ORG_NAME: DARTMOUTH-HITCHCOCK CLINIC

ORG_STATE: NH

PHR: This innovative and potentially paradigm shifting research in human subjects is important for public health because understanding the mechanisms underlying impaired resolution of inflammation in CF will have a critical impact on investigations of new therapeutic interventions for CF lung disease. Furthermore, the proposed research is germane to the NIH’s mission focusing on discoveries related to human disease pathogenesis and translation of these studies to clinical medicine.

PI_NAMEs: ASHARE, ALIX  (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Binding;Bronchiectasis;Bronchoscopy;CD14 gene;Cells;Chronic;chronic infection;Clinical Medicine;cohort;Cystic Fibrosis;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Data;differential expression;extracellular vesicles;Failure;Glycolysis;Goals;human disease;human subject;Immune;Impairment;improved;Inflammation;Inflammatory;Inflammatory Response;innovation;Investigation;Knowledge;Lipids;Longevity;Lung;Lung infections;Macrophage;Mediating;Metabolic Pathway;Metabolism;MicroRNAs;Mission;Morbidity - disease rate;Mutation;neutrophil;new therapeutic target;novel therapeutic intervention;Oxidative Stress;Pathogenesis;Persons;Phenotype;Population;prevent;Public Health;Pulmonary Cystic Fibrosis;Pulmonary Inflammation;Quality of life;Regulator Genes;Research;Resolution;Respiratory Failure;Sampling;Sorting;Surface;Testing;transcription factor;translational study;United States National Institutes of Health;vesicular release

PROJECT_TITLE: Mechanisms of Impaired Inflammation Resolution in Cystic Fibrosis Lung Disease

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Bioengineering;Cocaine;Drug Abuse (NIDA only);Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: GAINESVILLE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE: The proposed research is relevant to public health because facilitating accurate interpretation of fast voltammetric data is expected to help establish the precise role that specific neurochemicals play in regulating core brain processes and behavior. This is essential for the treatment of neurological disorders and maladaptive behaviors which are devastating, as well as difficult and costly to treat. Thus, the proposed research is relevant to the part of NIH’s mission that pertains to developing fundamental knowledge that will help to improve health and reduce the burdens of illness.

PI_NAMEs: SOMBERS, LESLIE A (contact)

PROGRAM_OFFICER_NAME: HILLERY, PAUL

PROJECT_TERMS: acquired factor;Address;Adoption;Affect;Animals;awake;Behavior;Brain;burden of illness;Calibration;Carbon;Cells;Chemicals;Cocaine;Cocaine Abuse;Compensation;Complex;Corpus striatum structure;cost;Coupled;Data;Data Analyses;data quality;Data Set;Development;Dopamine;electric impedance;Electrodes;Electron Transport;Environment;Evaluation;Event;experimental study;Feedback;Glutamates;Goals;Health;Hour;Implant;improved;In Situ;Individual;innovation;instrumentation;Investigation;Ions;Knowledge;Laboratories;macromolecule;maladaptive behavior;Maps;Measurement;method development;Methods;Microelectrodes;Microscopic;Mission;Monitor;Nature;Nervous System Disorder;neural;neurochemistry;Neurosciences;Neurotransmitters;Performance;Periodicity;pharmacologic;physical property;Play;Process;Public Health;Reaction;receptor;Research;Research Personnel;Resistance;Resolution;reuptake;Role;Scanning;Shapes;Signal Transduction;Slice;Source;Spectrum Analysis;Speed;Standardization;Surface;System;Techniques;Technology;Thinking;Time;Tissues;Training;treatment strategy;United States National Institutes of Health;usability;Work

PROJECT_TITLE: Expanding the Scope and Usability of Fast Voltammetric Measurements

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


NIH_SPENDING_CATS: Genetics;Hematology;Human Genome

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: NARRATIVE  One of the major vascular causes of death and disease in the USA is abnormal blood clots in the lung or feet, a condition called venous thromboembolism. Inheriting abnormal genes increases the risk of blood clots, but the genetic causes of abnormal blood clots are not well understood. We propose to study a new genetic pathway that increases the risk for abnormal blood clots, and our research may lead to improved risk prediction and new treatments to prevent and treat blood clots.

PI_NAMEs: LOWENSTEIN, CHARLES J (contact);OSBURN, WILLIAM OWEN

PROGRAM_OFFICER_NAME: KINDZELSKI, ANDREI L

PROJECT_TERMS: Adhesions;Affect;Animal Model;Automobile Driving;BCL1 Oncogene;BCL6 gene;Binding;Bioinformatics;Biological;Bleeding time procedure;Blood coagulation;Blood Coagulation Factor;Blood Coagulation Factor VII;Blood Platelets;Blood Vessels;Candidate Disease Gene;Cause of Death;Cell Line;Cell model;Cells;Chemicals;Chromatin Structure;Coagulation Factor Gene;Coagulation Process;Complex;conditional knockout;CRISPR/Cas technology;Data;Disease;Enhancers;Epigenetic Process;epigenetic regulation;experimental study;F7 gene;Family member;Fibrin;foot;Gene Abnormality;Gene Expression;Genes;Genetic;genetic corepressor;Genetic Enhancer Element;Genetic Risk;Genetic study;Genetic Transcription;genetic variant;Genome;genome wide association study;genomic locus;Goals;Grant;Hemorrhage;Hemostatic function;Hepatic;Hepatocyte;histone modification;Human;Human Genetics;improved;In Vitro;in vivo;inhibitor;Injury;innovation;knock-down;Knockout Mice;Knowledge;Label;Link;Liver;Lung;Mediating;member;Molecular;molecular modeling;Morbidity - disease rate;mortality;Mus;Mutagenesis;new therapeutic target;novel;novel therapeutics;Pathogenesis;Pathway interactions;Phenotype;Plasma;Play;Polycomb;PRC1 Protein;prevent;Production;Proteins;Prothrombin time assay;Regulation;Repressor Proteins;Research;Risk;risk prediction;risk variant;Role;Signal Transduction;Single Nucleotide Polymorphism;Single Nucleotide Polymorphism Map;Testing;Thrombosis;Thrombus;transcription factor;venous thromboembolism

PROJECT_TITLE: BCOR Regulation of Venous Thromboembolism

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IVBH-V (02)]


NIH_SPENDING_CATS: Bioengineering;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Health Relevance/Narrative: Liver cells from fetal liver can provide a unique regenerative cell source to generate new healthy tissue mass. We have identified the underlying mechanism and developed methods to produce similar growth- advantaged cells in vitro. Our studies will dissect the mechanism of cell competition/fitness and how it impacts chronic liver disease progression. Results from our proposed studies will provide new information for developing novel cell-based therapies in patients with liver disease.

PI_NAMEs: EBRAHIMKHANI, MO REZA;OERTEL, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: activin A;Activin Receptor;Adult;Aging;Alcoholic Liver Diseases;Animal Model;antagonist;Apoptosis;Automobile Driving;Bar Codes;Biological Process;Blood Vessels;Cell Cycle;Cell Differentiation process;cell injury;Cell Therapy;Cell Transplantation;Cells;Chemicals;chronic liver disease;Cirrhosis;Clinical;Competitive Behavior;Data;Development;Disease Progression;Engineering;Engraftment;Ethics;Exhibits;Fetal Liver;Fibrosis;fitness;functional restoration;Genes;Genetic;Growth;Health;Hepatic;Hepatic Mass;Hepatocyte;Hepatocyte transplantation;Human;human induced pluripotent stem cells;In Vitro;in vivo;induced pluripotent stem cell;Infusion procedures;inhibitor;injured;Knowledge;Liver;liver cell proliferation;Liver Cirrhosis;Liver diseases;Liver Fibrosis;liver inflammation;liver injury;liver repair;Liver Stem Cell;Mediating;Metabolic;Metabolism;Methods;Modeling;Molecular;Molecular Profiling;Mutate;Natural regeneration;next generation;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel therapeutic intervention;Oncogenic;Organ;Organoids;overexpression;Pathway interactions;Patients;Population;progenitor;Proliferating;Publishing;Rattus;receptor;receptor expression;regenerative;regenerative cell;replacement tissue;Resistance;senescence;Signal Pathway;Signal Transduction;small molecule;Source;stem cell derived tissues;stem cells;Technology;Testing;Therapeutic;Tissues;transplant model;Transplantation;vector;Virus

PROJECT_TITLE: Combating Chronic Liver Diseases via Understanding and Engineering Cell Competition and Fitness

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Liver Disease;Nutrition;Obesity;Prevention

ORG_DEPT: NEUROSCIENCES

PHR: Mice lacking the NADP(H) phosphatase, Nocturnin, are resistant to diet-induced obesity and hepatic steatosis on a high-fat diet, yet the mechanisms underlying this phenotype are unknown. In the experiments outlined in this proposal, we will subject adipose-, liver-, muscle-, and intestine-specific Nocturnin knock-out mice to a high- fat diet and analyze their adiposity and overall metabolic health. From these experiments, we will be able to both determine if loss of Nocturnin in a single tissue is sufficient to confer resistance to diet-induced obesity and better understand Nocturnin’s, and thus NADP(H)’s, tissue-specific impact on metabolism.

PI_NAMEs: GREEN, CARLA B. (contact);TAKAHASHI, JOSEPH S

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Adipocytes;adipokines;adiponectin;Adipose tissue;Affect;Body Composition;Body Weight;Calories;cell type;Cells;Cholesterol;Chylomicrons;circadian;Circulation;cofactor;conditional knockout;Cre driver;Cre lox recombination system;Cytoprotection;Darkness;Data;Deposition;Development;diet-induced obesity;Disease;Dissection;Eating;Electrons;Energy Metabolism;Enzymes;Exhibits;experimental study;Fatty acid glycerol esters;fatty acid oxidation;Fatty Acids;Fatty Liver;Female;Gene Expression;Genetic;Genotype;Health;High Fat Diet;Histology;Individual;Intestines;Knockout Mice;Leptin;lipid biosynthesis;Lipid Mobilization;lipid transport;Lipids;Lipoproteins;Liver;male;Measurement;Measures;Metabolic;Metabolism;Modeling;Molecular;Morphology;mRNA Expression;Mus;Muscle;NADP;nocturnin;Nonesterified Fatty Acids;novel therapeutics;Obesity;Obesity associated disease;obesity treatment;Olive oil preparation;Oxidative Stress;Pathway interactions;Periodicity;Phase;Phenotype;Phosphoric Monoester Hydrolases;Plasma;Population;Prevalence;prevent;Primary carcinoma of the liver cells;programs;Reaction;Resistance;Risk Factors;Role;Testing;therapy development;Thinness;Time;Tissues;transcriptome;transcriptome sequencing;Triglycerides;Very low density lipoprotein;Wild Type Mouse

PROJECT_TITLE: Genetic dissection of tissue-specific roles of a circadian NADPH phosphatase

STUDY_SECTION: CSRS

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome

ORG_NAME: DANA-FARBER CANCER INST

PHR: Colorectal cancer is the second most deadly cancer worldwide and responsible for an alarming trend of rising incidence among younger adults. Cell state plasticity by way of impaired differentiation contributes to cancer initiation, molecular heterogeneity, and resistance to targeted therapies. The proposed research will utilize rigorous model systems and cutting-edge scientific tools to define key mechanisms underlying cell state plasticity and impaired differentiation, aiming to provide original conceptual insights and stimulate new strategies for therapeutic development.

PI_NAMEs: SETHI, NILAY  (contact)

PROGRAM_OFFICER_NAME: LIU, ZHIHUI

PROJECT_TERMS: Address;adenoma;advanced disease;Algorithms;ATAC-seq;Binding;Biological Models;Biology;Biotechnology;cancer cell;cancer initiation;Cancer Model;Carcinogens;Cell Line;Cells;cellular engineering;Chromatin;Cleavage Under Targets and Release Using Nuclease;colon cancer cell line;Colorectal Cancer;colorectal cancer progression;Combination Drug Therapy;Complex;Credentialing;CRISPR screen;Custom;Data;Dependence;Deposition;Development;disabled;Engineering;Enhancers;Evaluation;Exhibits;fetal;Foundations;functional genomics;Gastroenterology;Gene Expression;Genes;Genetic;Genetic Screening;genetic selection;Genetic Transcription;Genetically Engineered Mouse;genome-wide;Genomic approach;Glycoproteins;Goals;Heterogeneity;Histones;Histopathology;Human;Human Engineering;human model;Impairment;In Vitro;in vivo;Incidence;innovation;insight;Interruption;intestinal epithelium;Intestines;Investigation;Knowledge;Link;Malignant - descriptor;Malignant Neoplasms;Mediating;Mediator;Messenger RNA;Methods;Modeling;Molecular;mortality;mouse genetics;mouse model;Mutation;neoplastic cell;next generation;novel therapeutic intervention;Oncogenes;Organoids;overexpression;patient subsets;Patients;Pharmaceutical Preparations;Phenotype;programs;Proteins;Regulation;Regulatory Element;Reporter;Research;Resistance;restoration;Role;Science;Series;single cell ATAC-seq;single-cell RNA sequencing;stemness;System;TACSTD2 gene;targeted agent;targeted treatment;Testing;Therapeutic;therapeutic development;therapeutic target;therapy design;therapy development;tool;Toxic effect;transcription factor;transcriptome sequencing;treatment response;trend;Tumor Burden;tumor growth;young adult

PROJECT_TITLE: Molecular mechanisms of developmental reprogramming in colorectal cancer

STUDY_SECTION: GRIC

STUDY_SECTION_NAME: Gene Regulation in Cancer Study Section[GRIC]


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Integrating histology image data to predict spatial gene expression in large-scale spatial transcriptomics (ST) studies is a promising approach. This application aims to develop informatics tools to conduct such predictions and implement them in open-source software packages. With these tools, researchers can generate virtual ST data at single-cell resolution, enabling 3D ST tissue volume reconstruction, exploration of spatial gene expression variations in population-based studies, and the creation of prognostic models.

PI_NAMEs: LI, MINGYAO  (contact)

PROGRAM_OFFICER_NAME: FARRELL, CATHERINE MARY

PROJECT_TERMS: 3-Dimensional;Address;Adoption;Algorithms;Area;biobank;Biological;Biomedical Research;Budgets;Cells;Characteristics;Clinical;Cloud Computing;collaborative environment;commercialization;Communities;Complex;computational platform;Computer software;cost;cost effective;cost efficient;Data;Data Analyses;data integration;design;Detection;Development;diagnosis standard;Disease;Ensure;experience;Feedback;Fostering;Gene Expression;Gene Expression Profile;gene expression variation;Generations;Genes;Goals;Hematoxylin and Eosin Staining Method;Histologic;histological image;Histology;Histopathology;Image;informatics tool;innovation;insight;interest;Investigation;Literature;Location;Methods;novel strategies;open source;Outcome;Pathology;Phase;Population;population based;Population Study;predictive modeling;preservation;prognostic model;reconstruction;Research;Research Design;Research Personnel;Resolution;Sampling;Stains;success;Techniques;Technology;Time;tissue reconstruction;Tissue Sample;Tissues;tool;Training;training data;transcriptomics;tumor microenvironment;usability;user-friendly;virtual;Visualization

PROJECT_TITLE: Developing informatics tools to predict virtual spatial transcriptomics data with single-cell resolution in large-scale studies

STUDY_SECTION: BLR

STUDY_SECTION_NAME: Biomedical Informatics, Library and Data Sciences Review Committee[BLR]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Mental Health;Neurosciences;Rehabilitation

ORG_NAME: MASSACHUSETTS EYE AND EAR INFIRMARY

PHR: This project will test the capability of a vestibular prosthesis (or implant) to improve cognitive function in patients with severe vestibular damage. We will measure how higher-level behaviors, including spatial orientation, navigation, and neuropsychologic function, are affected by long-term stimulation provided by the vestibular implant, and in parallel will study these behaviors in non-implanted patients with different degrees of vestibular impairment. The goal of these studies is to determine if the cognitive dysfunction experienced by patients with severe vestibular damage can be improved with prosthetic stimulation, findings which would expand the clinical utility of the vestibular implant while concomitantly improving understanding of the role of vestibular information in cognition.

PI_NAMEs: LEWIS, RICHARD F (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: 3-Dimensional;Acceleration;Adult;Affect;analog;Animal Model;Animals;Area;Behavior;behavioral study;Bilateral;Brain;brain fog;Child;Chronic;Chronic disability;Clinical;clinical development;Cochlear Implants;Cognition;Cognitive;Cognitive deficits;cognitive function;cognitive process;cognitive testing;Cues;Data;Development;disability;Disabling;Dizziness;Equilibrium;experience;Eye Movements;Force of Gravity;Gait;Goals;Head;Hippocampus;Human;human subject;Impaired cognition;Impairment;Implant;Implanted Electrodes;improved;Knowledge;Measures;Mediating;Motor;motor deficit;Neurobehavioral Manifestations;Neuropsychology;Outcome Measure;Patient Outcomes Assessments;Patients;Pattern;Performance;Peripheral;Physical therapy;Postural response;Posture;programs;Prosthesis;Quality of life;Reflex action;Research;response;restoration;Rodent;Role;Scientific Advances and Accomplishments;Semicircular canal structure;Severities;Signal Transduction;Space Perception;Symptoms;Testing;time use;Universities;Vestibular dysfunction;Vestibular function;Vestibular loss;vestibular prosthesis;vestibular system;vestibulo-ocular reflex;Vision;Visual;Visuospatial;Work

PROJECT_TITLE: Vestibular implant tested in patients with peripheral vestibular damage: effects on spatial orientation, navigation, and neuropsychologic function

STUDY_SECTION: SMN

STUDY_SECTION_NAME: Sensory-Motor Neuroscience Study Section[SMN]


ADMINISTERING_IC: OH

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Diisocyanates are essential industrial chemicals for making polyurethane and are a major cause of occupational asthma. This application aims to elucidate the unique mechanisms by which these chemicals cause disease, and biomarkers of exposure for disease screening/prevention.

PI_NAMEs: WISNEWSKI, ADAM  (contact)

PROGRAM_OFFICER_NAME: O'NEILL, EDUARDO

PROJECT_TITLE: Deciphering Occupational Asthma Pathogenesis Caused by Isocyanate

STUDY_SECTION: SOH

STUDY_SECTION_NAME: Safety and Occupational Health Study Section[SOH]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Esophageal Cancer;Rare Diseases;Stomach Cancer

PHR: People and parity are among the central tenets of public health efforts, and improving the design and implementation of NCI-sponsored clinical trials can directly improve patient access and survival. The work proposed in this R50 submission seeks to enhance the matching of NCI-sponsored trials and optimize resource allocation both locally and nationally, which will improve accrual and expedite successful trial completion. Increasing the speed at which we answer clinical questions in NCI- sponsored trials has direct impacts on enhancing health and lengthening life in gastrointestinal cancers.

PI_NAMEs: KLEMPNER, SAMUEL J (contact)

PROGRAM_OFFICER_NAME: LINDWASSER, ONN WOLF

PROJECT_TERMS: Address;Advisory Committees;Altruism;Award;Biological Markers;Clinical;Clinical Research;Clinical Trials;Communities;Dedications;demographics;design;experience;gastroesophageal adenocarcinoma;gastroesophageal cancer;Goals;Health;improved;Infrastructure;Institution;Institutional Review Boards;Lead;Leadership;Life;Malignant neoplasm of gastrointestinal tract;next generation;novel;parity;Patients;Persons;pragmatic trial;Program Evaluation;programs;Public Health;Renaissance;Research;Resource Allocation;Role;Site;Specialist;Speed;Work

PROJECT_TITLE: Steering the next generation of NCI-sponsored clinical trials in gastroesophageal cancers


NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Narrative. New evidence that the LGR5+ CSCs are not the sole driving force behind CRC progression and resistance to therapy took the community by surprise13 and suggested a more complex interplay between LGR5+ and LGR5- cells. We and others have recently uncovered the presence of a second stem cell population (OnFSCs) in CRC. Here, we aim to promptly assess their functional relevance in CRC evolution and define potentially targetable vulnerabilities.

PI_NAMEs: MZOUGHI, SLIM  (contact)

PROGRAM_OFFICER_NAME: YASSIN, RIHAB R

PROJECT_TERMS: 3-Dimensional;Ablation;Accounting;Address;Adenocarcinoma;adenoma;Adjuvant Therapy;advanced disease;Automobile Driving;Benign;Bypass;Cancer Biology;Cancer Etiology;cancer recurrence;cancer stem cell;cancer type;Cells;Cessation of life;Characteristics;Clinical;Colon;Colorectal Cancer;colorectal cancer progression;colorectal cancer treatment;Combined Modality Therapy;Communities;Complex;Coupled;Coupling;Death Rate;design;Diagnosis;driving force;Drug Combinations;drug use screening;Ecosystem;Ensure;Epigenetic Process;Epithelium;Evaluation;Evolution;fetal;Foundations;Gatekeeping;Gene Expression Profile;Genetic;Genetic Transcription;Goals;Growth;Human;in vivo;insight;intestinal epithelium;intestinal tumorigenesis;Knowledge;leukemia;LGR5 gene;Maintenance;Malignant - descriptor;Malignant Neoplasms;malignant phenotype;Modeling;Molecular;mortality;mouse model;multiple omics;Mus;Names;Neoplasm Metastasis;Nomenclature;novel;Operative Surgical Procedures;Organoids;Patients;Phenotype;Population;prevent;Recovery;Recurrence;regeneration potential;regenerative;Reporter;Reporting;Resistance;Resources;response;Role;screening;single cell sequencing;Solid;standard of care;stem cell population;stem cells;suicide gene;targeted treatment;Testing;Therapeutic;therapeutically effective;therapy resistant;Thinking;transcription factor;tumor;Tumor Expansion;tumor growth;Work;Xenograft procedure

PROJECT_TITLE: Functional and molecular characterization of Oncofetal Stem Cells in CRC

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Public Health Relevance: Heart disease is the leading cause of morbidity and mortality in the United States. This proposal aims to delineate the molecular mechanisms underlying the transformation of cardiac fibroblasts (CFs) into myofibroblasts and the reprogramming of CFs into induced cardiomyocytes, with the goal of leveraging the new knowledge of CF biology for reducing fibrotic scarring and regenerating lost myocardium in heart diseases.

PI_NAMEs: LIU, JIANDONG  (contact)

PROGRAM_OFFICER_NAME: POIZAT, CORALIE ISABELLE

PROJECT_TERMS: Abbreviations;Ablation;Acceleration;Accounting;Acute myocardial infarction;Address;Adult;Animal Model;ATAC-seq;Attenuated;Biology;Cardiac;Cardiac Myocytes;cardiac regeneration;Cardiovascular Diseases;Cardiovascular system;cell type;Cells;Cessation of life;ChIP-seq;Chromatin;Cicatrix;coronary fibrosis;Cytoplasmic Granules;Cytosol;Data;Development;DNA Binding;essays;experimental study;Extracellular Matrix;Extracellular Matrix Proteins;Fibroblasts;Fibrosis;Foundations;GATA4 gene;Gene Expression;Gene Expression Regulation;Generations;Goals;Heart Diseases;Heart failure;heart function;Heart Injuries;High Prevalence;Homeostasis;improved;in vivo;Induced Cardiomyocytes;Injury;interest;Investigation;Knock-out;Knowledge;Life Cycle Stages;lipid nanoparticle;Liquid substance;Mechanics;Mediating;Messenger RNA;Molecular;Morbidity - disease rate;mortality;mRNA delivery;Myocardial Infarction;Myocardium;Myofibroblast;Natural regeneration;novel;Pathologic;Patients;Phase;Phenotype;Play;Polyribosomes;Population;Post-Transcriptional Regulation;Prevalence;public health relevance;Reagent;Regenerative capacity;Ribonucleoproteins;RNA Splicing;RNA-Binding Proteins;Role;scaffold;Series;single-cell RNA sequencing;Testing;Therapeutic;Tissues;tool;transcription factor;Transcriptional Regulation;transcriptome;Translating;Translational Repression;Translations;translatome;United States

PROJECT_TITLE: Role of RBP in programming and reprogramming of cardiac fibroblasts

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDD-Q (81)]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Social Determinants of Health;Substance Misuse;Telehealth;Women's Health Research

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PSYCHIATRY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: NARRATIVE Over the past decade, alcohol consumption in the US has risen by 84% in women compared with 35% in men. Given that women experience accelerated health-related problems at lower consumption levels (“telescoping”), and there are no approved medications tailored to the unique needs of women, this presents a public health crisis. We propose a multicenter clinical trial, conducted using a remote platform, to examine whether guanfacine extended release (GXR; 3mg/d) versus placebo can reduce drinking in women with Alcohol Use Disorder (AUD) by targeting biological and behavioral processes integral to compulsive drinking in women.

PI_NAMEs: FOX, HELEN CECILIA (contact)

PROGRAM_OFFICER_NAME: SENEVIRATNE, CHAMINDI

PROJECT_TERMS: Acceleration;adherence rate;Agonist;Alcohol consumption;alcohol craving;alcohol monitoring;alcohol relapse;alcohol use disorder;Alcohols;Anxiety;Arousal;Attenuated;Behavioral;binge drinking;biobehavior;Biological;caregiving;Cellular Phone;Characteristics;Clinical;Clinical Trials;Consumption;Controlled Clinical Trials;cost effective;craving;Data;design;Disadvantaged;Double-Blind Method;drinking;Ecological momentary assessment;efficacy evaluation;emotion dysregulation;emotion regulation;experience;FDA approved;Gender;Guanfacine;Health;health disparity;Heavy Drinking;Hour;Laboratories;Measurement;Medical;medication compliance;men;Mental Health;Methods;mood regulation;Moods;Motivation;Multi-Institutional Clinical Trial;Multicenter Trials;negative mood;Norepinephrine;parity;Participant;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacodynamics;Phase;pill;Placebo Control;Placebos;postsynaptic;pre-clinical;presynaptic;primary outcome;Process;prospective;Public Health;Randomized;Rattus;receptor;recruit;Relapse;relapse prevention;remote visit;Reporting;Research;Riboflavin;Risk;Risk Factors;safety assessment;Sampling;secondary outcome;self-reported anxiety;Severities;sex;Shame;Site;social stigma;Solid;Stigmatization;Stress;substance use;Techniques;Technology;telehealth;Time;treatment group;United States Substance Abuse and Mental Health Services Administration;Urine;Use Effectiveness;Visit;week trial;Woman;women versus men

PROJECT_TITLE: Guanfacine for women with AUD: A multisite study using a telehealth approach

STUDY_SECTION: AA

STUDY_SECTION_NAME: Clinical, Treatment and Health Services Research Study Section[AA-3]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cystic Fibrosis;Gene Therapy;Genetics;Human Genome;Lung;Nanotechnology;Orphan Drug;Rare Diseases

ORG_CITY: TORONTO

ORG_COUNTRY: CANADA

ORG_FIPS: CA

ORG_NAME: UNIVERSITY OF TORONTO

ORG_STATE: ON

ORG_ZIPCODE: M5S 1S8

PHR: SPECIFIC AIMS Current therapies for cystic fibrosis (CF) are insufficient for a large segment of American patients, particularly those harboring CFTR nonsense mutations (NMs). This gap in treatment options signifies a critical unmet medical need, as these mutations represent the most common genetic variants causing CF, yet remain largely unaddressed by existing therapies. To address this therapeutic void, we aim to develop a non-viral base-editing approach specifically designed to correct such mutations. Specific Aim 1: In Vitro Optimization and Characterization of RNA-Encoded ABE Systems This aim focuses on the refinement and characterization of RNA-encoded Adenine Base Editors (ABEs) for in vitro applications, targeting the G542X mutation in the CFTR gene associated with CF. Sub-aim 1.1 is devoted to the synthesis and optimization of chemically modified ABE mRNA to enhance its stability and cellular uptake. Sub-aim 1.2 aims to fine-tune guide RNA (gRNA) configurations to maximize base-editing efficacy while minimizing off-target risks. Sub-aim 1.3 explores the functional recovery of CFTR post-base editing. Utilizing the 16HBEge CFTR G542X cell line as our disease model, we will employ the second-generation PAM-less Cas9 variant, CE-8e-SpRY, which has shown superior performance in preliminary studies. Various methodologies, such as in vitro transcription, gel-based cleavage, and Ussing Chamber assays, will be implemented for comprehensive validation. Specific Aim 2: Development and Screening of LNPs for Pulmonary Delivery of ABE Systems The objective of this aim is to engineer optimized lipid nanoparticles (LNPs) for efficient pulmonary delivery of ABEs. To address key challenges like mucus barrier penetration and endosomal escape, our approach incorporates a high-throughput combinatorial synthesis (HTCS) platform for formulating a novel library of ionizable lipids. A two-tiered screening process will initially be performed in 2D human bronchial cell cultures, followed by ex vivo validation in air-liquid interface (ALI) 3D cultures. The most promising LNP candidates will undergo in vivo testing in murine models, offering a robust, iterative optimization process. Specific Aim 3: Efficacy and Safety Assessment of ABE LNPs in CFTR G542X Mouse Models The overarching objective of this aim is to rigorously evaluate the efficacy and safety of LNP-encapsulated ABEs in a CFTR G542X mouse model, which faithfully replicates the cardinal features of CF. Leveraging the targeted lung delivery of LNPs, we expect to mitigate the risks of off-target effects compared to systemic delivery. Sub- aim 3.1 focuses on the re-optimization of gRNA sequences for mouse primary lung epithelial cells, evaluating both A>G editing efficiency and edit purity. Sub-aim 3.2 involves intratracheal administration of optimized ABE LNPs at variable dosages, assessing therapeutic impact through nasal potential difference (NPD) and genomic analyses. Sub-aim 3.3 will undertake exhaustive molecular scrutiny of potential off-target editing events, utilizing whole-genome sequencing for definitive verification. Anticipated outcomes include the restoration of functional CFTR protein in over 10% of treated mice with minimal off-target events. In the near term, our research endeavors to offer a transformative base-editing treatment for CF patients harboring the G542X mutation. In the long run, this strategy could extend its applicability to approximately 12% of all inherited diseases caused by NMs, many of which are currently without effective treatments. This would constitute a significant advance in gene therapy for CF, filling a critical gap in patient care while also pioneering techniques in RNA and genome editor delivery systems. Upon successful completion of this research, future work will involve the further optimization of LNP-carrying RNA-encoded ABEs for stability in nebulizers, enhancing the translatability of our approach and potentially catalyzing substantial advancements in American health sciences.

PI_NAMEs: LI, BOWEN  (contact)

PROJECT_TERMS: Address;Adenine;Air;American;base editing;base editor;Biological Assay;Cell Culture Techniques;Cell Line;cellular engineering;Chemicals;Clinical;combinatorial;Combinatorial Synthesis;Cystic Fibrosis;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;design;Development;Disease;disease model;dosage;effective therapy;efficacy evaluation;Encapsulated;Endosomes;Engineering;Epithelial Cells;Event;Formulation;Foundations;functional restoration;Future;Gel;gene therapy;Generations;Genes;Genetic Diseases;Genetic Transcription;genetic variant;genome editor;genome sequencing;Genomic medicine;Genomics;Guide RNA;Health Sciences;Hereditary Disease;Human;In Vitro;in vivo;in vivo evaluation;innovation;Libraries;Lipid Chemistry;lipid nanoparticle;Lipids;Liquid substance;Lung;Lung Diseases;Mediating;Medical;Messenger RNA;Methodology;Molecular;mouse model;Mucous body substance;Mus;Mutation;nanoparticle;Nebulizer;Nonsense Mutation;Nose;novel;Other Genetics;Outcome;Pancreas;Patient Care;Patients;Penetration;Performance;premature;Process;process optimization;protein expression;Proteins;Recovery of Function;Regulator Genes;Research;Risk;risk mitigation;RNA;RNA Sequences;Safety;safety assessment;screening;stem;System;Techniques;Technology;Terminator Codon;Therapeutic;therapeutically effective;three dimensional cell culture;Treatment Efficacy;Treatment Protocols;uptake;Validation;Variant;whole genome;Work

PROJECT_TITLE: Combinatorial design of nonviral base editing systems for treating cystic fibrosis with nonsense mutations

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-X (81)]


ADMINISTERING_IC: AG

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Prevention;Social Determinants of Health;Vaccine Related

ORG_DEPT: MISCELLANEOUS

PHR: Project Narrative We inform evidence-based policies to address inequities and improve public health when resources are scarce and specifically inform the impact of policies that target early access by geographic vs. individual- level health, social vulnerability, and race by using a large randomized experiment that took place when vaccines were extremely scarce to estimate inequities in vaccine takeup among patients age ≥65 that persist given randomized early access. We quantify the potential equity impacts of further public health policies that go beyond targeting greater numbers of invitations by quantifying how much of the inequities that persist given randomized early access can be explained by various mechanisms that operate through health behaviors, health conditions, and social and environmental factors available in our rich population-level data, which we plan to disseminate. We inform the potential for vaccine distribution policies to affect current and future inequities in health and economic wellbeing by adapting a well founded framework from economics to characterize how the composition of the vaccinated population changes by health, social vulnerability, and race as the share vaccinated expands with randomization and by relating those changes to inequities in the downstream impact of vaccination.

PI_NAMEs: KOWALSKI, AMANDA ELLEN (contact)

PROGRAM_OFFICER_NAME: KIM, THERESA YOUNGJOO

PROJECT_TERMS: Address;Affect;Age;Alzheimer's disease related dementia;Behavior;Cessation of life;Characteristics;critical period;Data;Data Set;Dimensions;Disparity;Dose;Economics;Electronic Health Record;Eligibility Determination;Environmental Risk Factor;Equitable healthcare;Equity;evidence base;experimental study;follow-up;Future;Geography;Goals;Health;Health behavior;health care delivery;health disparity;health inequalities;Health Policy;Health Resources;Health Surveys;Hospitals;human old age (65+);improved;Individual;Inequity;Letters;Life;Link;Literature;Medicine;Methods;Michigan;Natural experiment;novel;Outcome;outcome disparities;pandemic disease;patient population;Patient Self-Report;Patients;Personal Satisfaction;Persons;Policies;Policy Maker;Population;Positioning Attribute;Public Health;Race;Randomized;Registries;Research Design;Resources;Respiratory Disease;response;Risk Factors;risk mitigation;Site;social factors;social vulnerability;Sociology;Subgroup;supply chain;Surveys;System;Time;Vaccinated;Vaccination;vaccine access;vaccine distribution;Vaccines;Ventilator;Vulnerable Populations;Wages;young adult

PROJECT_TITLE: Tradeoffs Between the Equal and Equitable Distribution of a Scarce Health Resource: Evidence from a Large Randomized Natural Experiment with Targeting by Health, Social Vulnerability, and Race

STUDY_SECTION: ODHS

STUDY_SECTION_NAME: Organization and Delivery of Health Services Study Section[ODHS]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Physical Activity

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Narrative Heart failure patients with preserved ejection fraction (HFpEF) exhibit severe exercise limitation and exertional dyspnea and in this context, the central premise of our proposal is that locomotor and inspiratory muscle pathophysiologic mechanisms contribute to these HFpEF symptoms. In this application, we investigate the role the 1) locomotor muscle reflexes have on the abnormal cardiopulmonary responses during exercise in HFpEF patients, and 2) exaggerated inspiratory muscle blood flow demand during exercise (arising from inspiratory muscle inefficiency) have in contributing to exercise intolerance and exertional dyspnea in HFpEF patients. The novel mechanistic questions we have developed combined with the cutting-edge measurements, innovative experimental design, and use of a clinically relevant intervention (i.e., inspiratory muscle training) will provide new targets to intervene on to improve exercise tolerance and exertional symptomology for HFpEF patients.

PI_NAMEs: SMITH, JOSHUA R. (contact)

PROGRAM_OFFICER_NAME: TINSLEY, EMILY

PROJECT_TERMS: Address;Adult;associated symptom;Blood flow;Cardiopulmonary;Cardiovascular Abnormalities;Clinical;clinical translation;clinically relevant;comparison control;Contracts;Coupled;Data;Dyspnea;EFRAC;Exercise;exercise intolerance;Exercise Tolerance;Exertion;Exhibits;Experimental Designs;Feedback;Functional disorder;Goals;Heart failure;high risk;Impairment;improved;Infrastructure;innovation;Intervention;Leg;Lung;Measurement;Mechanics;Mediating;Metabolic;mortality;mortality risk;Muscle;National Heart, Lung, and Blood Institute;novel;Oxygen;Pathologic;Patients;Peripheral;Physiological;Play;preservation;programs;Protocols documentation;Reflex action;Research;Research Priority;Research Support;response;Role;Skeletal Muscle;Statistical Data Interpretation;Symptoms;Syndrome;System;Technical Expertise;Techniques;Testing;Training;United States National Institutes of Health;ventilation

PROJECT_TITLE: Peripheral mechanisms of exercise intolerance in HFpEF

STUDY_SECTION: CCHS

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Neurosciences;Rare Diseases

PHR: PROJECT NARRATIVE We propose using cutting-edge microelectrode recordings collected in the operating room to study unprecedented tumor-altered single cell activity at high resolution in the human brain in vivo paired with 3D computer vision-enabled mapping and direct electrical stimulation. This work will lead to a mechanistic basis for understanding how tumors alter activity in neurons and will allow us to test a novel high resolution diagnostic tool to generate a physiological map of the tumor boundary which could aid clinical decisions.

PI_NAMEs: PAULK, ANGELIQUE C (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: 3-Dimensional;Acceleration;activity marker;Age;Animals;Binding;Brain;brain cell;Brain Neoplasms;Brain region;brain tissue;Cells;Clinical;Complex;Computer Vision Systems;Data Set;Development;diagnostic tool;Electric Stimulation;Electrical Stimulation of the Brain;Electrodes;Epilepsy;epileptiform;Equilibrium;Excision;excitatory neuron;FDA approved;Feedback;Frequencies;Future;Glioma;Goals;Hair;Human;human tissue;image guided;Immunologics;improved;In Vitro;in vivo;Infiltration;Informed Consent;inhibitory neuron;Link;Literature;Magnetic Resonance Imaging;Malignant neoplasm of brain;Maps;Measures;Mediating;Methods;Microelectrodes;Molecular;neoplastic cell;neural;Neural Inhibition;Neuroepithelial, Perineurial, and Schwann Cell Neoplasm;Neuroglia;neuroimaging;neuronal tumor;Neurons;neurophysiology;neurosurgery;novel;novel diagnostics;Operating Rooms;Operative Surgical Procedures;Participant;Pathologic;Patients;Physiological;Physiology;Postoperative Period;Printing;Process;prospective;reconstruction;Reporting;Resected;Resolution;response;Sampling;Schedule;Seizures;Site;Surface;Surgical Oncology;Synapses;System;Technology;Testing;Thick;Tissue Sample;Tissues;tumor;Tumor Biology;tumor diagnosis;tumor microenvironment;Tumor-Associated Process;Work

PROJECT_TITLE: Neural Activity Signatures of Tumor Infiltration in the Human Brain

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


NIH_SPENDING_CATS: Data Science;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Biomedical datasets relevant to fundamental biology and human health are increasingly deposited in centralized databases, enabling opportunities to train powerful machine learning models and perform large-scale meta-analyses. Unfortunately, poor metadata in biomedical databases is currently a barrier to these opportunities and thus there is a critical need for metadata curation. We will develop machine learning methodologies for automated standardization and enhancement of biomedical metadata, allowing the information contained within centralized biomedical databases to be used to the fullest extent possible.

PI_NAMEs: DEWEY, COLIN NOEL (contact)

PROGRAM_OFFICER_NAME: REDDY, GOUTHAM

PROJECT_TERMS: Active Learning;Address;Biological;Biological Assay;Biology;biomedical ontology;Biomedical Research;cell type;Cells;central database;Chemicals;cost;Data;Data Aggregation;data integration;Data Set;Databases;deep learning;Deposition;Development;experimental study;Gene Expression;Gene Expression Profile;Health;Human;human disease;human RNA sequencing;interest;Label;large datasets;Liver;Machine Learning;machine learning classifier;machine learning method;machine learning model;Meta-Analysis;Metadata;Methods;Natural Language Processing;Ontology;Paper;Phenotype;Protocols documentation;Publications;Pythons;Research Personnel;Sampling;Sequence Read Archive;single-cell RNA sequencing;Source;Standardization;success;System;Text;Tissues;Training;training data;training opportunity;transcriptome;transcriptome sequencing;web interface;web-accessible;Work

PROJECT_TITLE: Automated methods for standardization and enhancement of metadata in biomedical databases

STUDY_SECTION_NAME: Special Emphasis Panel[ZLM1 AS-C (01)]


NIH_SPENDING_CATS: Genetics;Transplantation

ORG_DEPT: SURGERY

PHR: Project Narrative Effector B cells (Beff) can profoundly influence the immune response by expressing inflammatory mediators that promote transplant rejection and autoimmunity. However, lack of identifying markers make Beff difficult to study. Moreover, factors regulating the development and function of Beff are poorly understood leaving no approach to manipulate their activity. We have now discovered that TIM-4 identifies Beff that express a variety of pro-inflammatory effector molecules. Studies in this proposal will allow us to determine how these cells and their inflammatory mediators are regulated, providing critical insights necessary to manipulate their activity to promote allograft survival and inhibit autoimmunity.

PI_NAMEs: ROTHSTEIN, DAVID M (contact)

PROGRAM_OFFICER_NAME: KULKARNI, SHILPA S

PROJECT_TERMS: Acceleration;Address;allograft rejection;Allografting;anti-CD20;Antigens;antimicrobial;ATAC-seq;Attenuated;autocrine;Autoimmune;Autoimmune Diseases;Autoimmune Responses;Autoimmunity;B-Lymphocyte Subsets;B-Lymphocytes;Binding;Biology;biomarker identification;candidate identification;Cell Physiology;Cells;Cellular biology;Chimera organism;Chromatin;Chronic;Clinical;Colitis;Consensus;Cre driver;CRISPR screen;CRISPR/Cas technology;cytokine;Data;Development;Disease;Equilibrium;Exhibits;Experimental Autoimmune Encephalomyelitis;Gene Expression;Genes;Genetic Transcription;Graft Rejection;Graft Survival;Granulocyte-Macrophage Colony-Stimulating Factor;Heart Transplantation;Hematopoietic;Heterogeneity;Human;IL17 gene;Immune response;Immunologic Markers;improved;In Vitro;in vivo;Individual;Infection;Infiltration;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;insight;Interleukin-10;Interleukin-2;interleukin-22;interleukin-23;Interleukin-6;islet allograft;kidney allograft;Lentivirus Vector;Libraries;Maintenance;Mus;Nature;neuroinflammation;Organ;Pathogenicity;Pathway interactions;Patients;peripheral blood;Phenotype;Plasma Cells;Play;Population;Positioning Attribute;post-transplant;prevent;Production;Property;proteoglycan induced arthritis;Regulation;response;Role;Severities;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Somatic Cell;Specificity;systemic autoimmunity;T-Lymphocyte;Testing;Time;Tissues;transcription factor;transcriptome;transcriptome sequencing;Transplant Recipients;Transplantation;tumor;Vascular Diseases;whole genome;Work

PROJECT_TITLE: Proinflammatory B Cells Defined by TIM-4 in the Alloimmune Response

STUDY_SECTION: TTT

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_CITY: EAST LANSING

ORG_DEPT: CHEMISTRY

ORG_NAME: MICHIGAN STATE UNIVERSITY

PI_NAMEs: ANDORFER, MARY CATHERINE (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Investigation and application of hydrocarbon-degrading enzymes using cryo- electron microscopy and directed evolution

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Cancer;Childhood Leukemia;Genetics;Hematology;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Umbilical Cord Blood/ Placenta;Stem Cell Research - Umbilical Cord Blood/ Placenta - Human

PHR: PROJECT NARRATIVE  NUP98-NSD1 fusion-positive acute myeloid leukemia (AML) is a poor prognostic subtype in children and is frequently associated with co-occurring mutations in the transcription factor WT1. Focusing on the cellular and developmental context, our proposal aims to dissect mechanisms of action of the fusion oncoprotein NUP98- NSD1, investigate WT1's role in therapy resistance, and identify novel therapeutic targets for childhood AML. These results are poised to reshape our understanding of childhood susceptibility to AML and provide a rationale for therapeutic intervention in future clinical studies.

PI_NAMEs: WAGENBLAST, ELVIN  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute Myelocytic Leukemia;Adult;Age;antagonist;Birth;Bone Marrow;Candidate Disease Gene;Cells;Chemoresistance;chemotherapy;Child;Childhood;Childhood Acute Myeloid Leukemia;Childhood Leukemia;Chromatin;Chromosomal translocation;Chromosome 11;Chromosome 5;Clinical Research;cohort;CRISPR/Cas technology;Cytogenetics;Dependence;Development;Diagnosis;Disease;Disease-Free Survival;Early identification;Epigenetic Process;Experimental Models;experimental study;fetal;Fetal Development;Fetal Liver;fusion gene;Fusion Oncogene Proteins;Future;Gene Fusion;Genetic Predisposition to Disease;Genetic Transcription;Genome engineering;Goals;Gonadal Steroid Hormones;Growth;Hematopoietic stem cells;histone methyltransferase;Human;improved outcome;In Vitro;in vivo;in vivo Model;Intervention;Knock-out;leukemia;Leukemic Cell;leukemic stem cell;leukemic transformation;leukemogenesis;Ligands;loss of function mutation;Malignant Childhood Neoplasm;Malignant Neoplasms;Measures;Mediating;Mediator;member;Modeling;Molecular;Monozygotic twins;Mus;Mutation;mutational status;Myelogenous;new therapeutic target;Nuclear Fusion;Nuclear Pore Complex;NUP98 gene;Oncoproteins;Pathway interactions;Patients;pediatric patients;permissiveness;postnatal;postnatal human;Predisposition;prenatal;Prognosis;prognostic;programs;Proliferating;Protein Region;Receptor Signaling;Relapse;Repression;Research;Resistance;response;Role;Sampling;Shapes;single cell ATAC-seq;single-cell RNA sequencing;small molecule inhibitor;stem cells;Steroid Receptors;System;Testing;Therapeutic;Therapeutic Intervention;therapy resistant;transcription factor;Tumor Suppressor Proteins;Umbilical Cord Blood;WT1 gene;Xenograft procedure;Zinc Fingers

PROJECT_TITLE: Overcoming Therapy Resistance in Fusion Oncoprotein Driven Pediatric Leukemia

STUDY_SECTION: BCO

STUDY_SECTION_NAME: Biochemical and Cellular Oncogenesis Study Section[BCO]


NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PHR: Project Narrative Adoptive cellular therapy (ACT) has had dramatic impact on patients with blood cancers, however, these transferred immune cell therapies have a high relapse rate of >50% as they rarely lead to long-term functional anti-cancer immunity. Blood stem cells can be modified to express a chimeric antigen receptor (CAR), which would continuously renew cancer-targeted immune cells; however, in this case, all blood cell types, including those associated with cytokine release syndrome (CRS), would express the CAR, likely leading to unacceptable on-going risk of toxicity. Here, we propose to engineer the CAR vector so that blood stem cells stably carry the DNA (taking advantage of their ability to continuously re-populate all blood cell types and convey long-term anti- cancer immunity), while the mRNA, and thus the therapeutic protein, are only expressed in specific cancer- fighting immune cells, minimizing the risk of toxicity and enabling this therapeutic approach that can prevent relapse through long-lived anti-cancer immunity.

PI_NAMEs: SMITH, ERIC L (contact)

PROGRAM_OFFICER_NAME: HARRIS, RAYMOND D

PROJECT_TERMS: adaptive immunity;Address;Adoptive Cell Transfers;Adult;Adult Acute Lymphocytic Leukemia;Adult Lymphoma;anti-cancer;Antigen Targeting;Antigens;ATAC-seq;Autologous Transplantation;Automobile Driving;B-Cell Acute Lymphoblastic Leukemia;Biology;Blood Cells;blood treatment;CAR T cell therapy;CD94 Antigen;Cell Lineage;cell type;Cells;Cellular immunotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;comparative;computational pipelines;cytokine;cytokine release syndrome;Data;daughter cell;design;Development;Disease;Disease remission;DNA;Dose;Effector Cell;Engineering;Exclusion;exhaustion;fighting;follow-up;Foundations;functional loss;Future;Gene Expression;Gene Modified;Generations;Genetic;Genetic Transcription;Hematologic Neoplasms;Hematopoiesis;Hematopoietic;Hematopoietic Neoplasms;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Human;Immune;Immune Targeting;Immunologic Memory;Immunologic Receptors;Immunologic Surveillance;improved;in vivo;in vivo Model;Killer Cells;Lead;lead candidate;leukemia/lymphoma;Libraries;Lymphoma;Malignant Neoplasms;Mediating;Messenger RNA;MicroRNAs;Modeling;Modification;mouse model;Multiple Myeloma;Myeloid Cells;Natural Killer Cells;NK cell therapy;Nucleic Acid Regulatory Sequences;Patients;Phenotype;Plasma Cells;Policies;pre-clinical;premature;prevent;promoter;receptor expression;Refractory;Regulatory Element;Relapse;relapse patients;relapse prevention;Reproducibility;response;Risk;risk minimization;Safety;screening;Sorting;Specificity;stem cell genes;T-Lymphocyte;Therapeutic;therapeutic protein;Thymus Gland;Toxic effect;transcriptome sequencing;transgene expression;Transgenes;Translations;Transplantation;tumor;tumor growth;Tumor Immunity;tumorigenesis;vector;Work;Writing

PROJECT_TITLE: Harnessing naturally occurring cell type-specific regulatory elements and normal HSC hematopoiesis to develop cell lineage-controlled CAR expression and continuously renewing CAR NK cells

STUDY_SECTION: CIC

STUDY_SECTION_NAME: Cellular Immunotherapy of Cancer Study Section[CIC]


NIH_SPENDING_CATS: Lymphatic Research;Lymphedema

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: PROJECT NARRATIVE Lymphatic vessels act like miniature hearts to pump fluid from the tissues to prevent swelling, but these lymphatic pumps fail in lymphedema and contribute to a progressive and incurable swelling. This proposal is focused on determining how calcium handling in lymphatic muscle cells regulates lymphatic pumping and transcriptional control. We propose a set of experiments to investigate calcium signaling through a process called “store operated calcium entry” to maintain functional lymphatic muscle cells.

PI_NAMEs: ZAWIEJA, SCOTT D. (contact)

PROGRAM_OFFICER_NAME: CATANIA, SELEN MURATOGLU

PROJECT_TERMS: Acute;Address;Affect;Agonist;American;Calcium;Calcium Signaling;cancer survival;cell dedifferentiation;Cell membrane;Cell Physiology;Chronic;clinically significant;Contractile Proteins;Data;Dependence;Diabetes Mellitus;Edema;Electrophysiology (science);Endoplasmic Reticulum;Ensure;experimental study;Failure;Female;Fibrosis;Functional disorder;gain of function;Gene Expression;Generations;Genetic Transcription;Goals;Health;Heart;Homeostasis;Hypertension;Impairment;inducible Cre;Inositol;Intervention;Ion Channel;ITPR1 gene;Knockout Mice;Knowledge;Libraries;Limb structure;Link;Liquid substance;Lymphatic;lymphatic dysfunction;Lymphatic function;lymphatic pump;lymphatic vessel;Lymphedema;male;Measures;Mediating;Membrane Potentials;Modeling;Molecular;Morbid Obesity;Mus;Muscle Cells;Myography;new therapeutic target;novel;nuclear factors of activated T-cells;Nuclear Family;Obesity;Outcome;patch clamp;Pathogenesis;Pathologic;Patients;pharmacologic;Phenotype;Physiological;Play;pressure;Prevalence;prevent;Process;protein expression;Protein Isoforms;Proteins;Pump;receptor;Regulation;Reporting;response;Reverse Transcriptase Polymerase Chain Reaction;Risk Factors;Role;secondary lymphedema;sensor;Signal Transduction;single-cell RNA sequencing;Smooth Muscle;Smooth Muscle Myocytes;Source;Stimulus;superresolution microscopy;Swelling;T-Cell Activation;Testing;Tissues;transcription factor;transcription factor NF-AT c3;Transcriptional Regulation;Treatment-Related Cancer;tripolyphosphate;voltage

PROJECT_TITLE: Regulation of lymphatic muscle cell function by store operated calcium entry signaling

STUDY_SECTION: IVPP

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


PHR: PROJECT NARRATIVE This research seeks to enhance public health by pinpointing genetic markers that can forecast who is at risk for serious side effects from widely-used cancer immunotherapies, thereby enabling personalized treatment plans. By investigating how these genetic factors interact with immunological and somatic variables, we aim to improve the safety profile of these therapies, reducing healthcare burdens associated with treatment complications. The project has the potential to minimize treatment-related complications on a broad scale, thereby enhancing the overall quality of healthcare and contributing to a reduction in illness and disability across the population.

PI_NAMEs: CHOUEIRI, TONI  (contact);GUSEV, ALEXANDER

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: 9p21;Adrenal Cortex Hormones;Antitumor Response;Asian population;Autoimmune;Autoimmune Diseases;Biological;Biological Response Modifiers;Blood;cancer immunotherapy;Cancer Patient;cancer subtypes;cancer therapy;cancer type;cell type;Cells;Cessation of life;Clinical;Clinical Data;Clinical Management;Clinical Trials;cohort;Data;Development;disability;efficacy outcomes;Environment;European ancestry;Event;Exhibits;Gene Expression;Gene Frequency;Genetic;genetic architecture;genetic makeup;Genetic Markers;Genetic study;genome wide association study;Genomics;Germ Lines;Germ-Line Mutation;Goals;health care quality;healthcare burden;Heritability;Hospitalization;IL7 gene;Immune;Immune checkpoint inhibitor;immune-related adverse events;Immunologics;Immunology;Immunotherapeutic agent;Immunotherapy;improved;Individual;Infiltration;inhibitor therapy;insight;Interruption;large datasets;Link;Malignant Neoplasms;Melanoma;Modeling;molecular scale;Mutation;novel;Organ;Outcome;Patients;personalized immunotherapy;personalized medicine;Population;Public Health;Randomized;relapse risk;Renal Cell Carcinoma;Research;Resistance;response;Risk;Safety;safety outcomes;Serious Adverse Event;Shapes;Side;side effect;single-cell RNA sequencing;Specificity;Toxic effect;transcriptome sequencing;Treatment outcome;treatment planning;tumor;tumor microenvironment;Variant;Work

PROJECT_TITLE: Assessment of germline variants associated with immune-related adverse events following immune checkpoint inhibitors

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


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

ORG_CITY: ORANGEBURG

ORG_NAME: NATHAN S. KLINE INSTITUTE FOR PSYCH RES

PHR: NARRATIVE: Mitochondria, the essential energy-generating compartment within cells, including neurons, are dysfunctional during aging and in neurodegenerative disorders. We have identified mitovesicles, a small, mitochondria- derived vesicle secreted by cells, and have demonstrated that their amount and content are altered in brains with mitochondrial dysfunction. In this proposal, we will examine the role of mitovesicles in maintaining mitochondrial function in neurons, determining the interrelationship between the most important Alzheimer's disease-risk gene, apolipoprotein E, and mitovesicle generation, mitochondrial health, and the impact of the mitovesicle system on neuron function.

PI_NAMEs: LEVY, EFRAT  (contact);MATHEWS, PAUL M

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Affect;Age;Aging;Alleles;Alzheimer's disease risk;Animal Model;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;Biogenesis;Biology;Brain;brain tissue;Cell membrane;Cell secretion;Cell Survival;Cells;Cholesterol;Collaborations;Cytoprotection;Data;Defect;Diet;Disease;DNA;Electrophysiology (science);Endosomes;Excision;exosome;extracellular;Extracellular Space;extracellular vesicles;Fatty acid glycerol esters;Generations;Genotype;Health;Homeostasis;Human;Impairment;In Vitro;in vivo;Knowledge;late endosome;Lead;Link;Lipids;Long-Term Potentiation;Mediating;Memory;Mitochondria;mitochondrial dysfunction;Mitochondrial Proteins;Multivesicular Body;Mus;Neurodegenerative Disorders;Neurons;novel;Organelles;oxidative damage;Pathology;Pathway interactions;Physiological;postsynaptic;presynaptic;Production;Proteins;Quality Control;resilience;risk variant;RNA;Role;Stress;Supporting Cell;Synapses;synaptic function;System;Testing;Thinking;Toxic effect;transmission process;uptake;Vesicle;wasting

PROJECT_TITLE: Apolipoprotein E genotype modulates brain mitovesicle production, a component of mitochondrial quality control

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Congenital Structural Anomalies;Digestive Diseases;Genetics;Human Genome;Infant Mortality;Lung;Neonatal Respiratory Distress;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE The overall goal of this proposal is to identify and validate novel genes and variants that cause congenital diaphragmatic hernia (CDH), a common and severe birth defect that is poorly understood. We will use genomic data from our large, well-characterized CDH patient cohort to identify novel genes and variants associated with CDH, and prioritize these genes and variants for validation in mouse models. Using advanced genome editing approaches, we will validate candidate variants and study promising hits in depth, providing insight into the genetics and mechanisms that underly CDH pathology.

PI_NAMEs: HIGH, FRANCES ARIANWEN;MURRAY, STEPHEN A (contact)

PROGRAM_OFFICER_NAME: TOYAMA, REIKO

PROJECT_TERMS: Accounting;Affect;Alleles;Animal Model;Animals;Appearance;Breeding;Bypass;Candidate Disease Gene;candidate validation;Cell Proliferation;cell type;Cells;Characteristics;Child;clinical phenotype;ClinVar;Clustered Regularly Interspaced Short Palindromic Repeats;Code;cohort;conditional knockout;Congenital Abnormality;congenital anomaly;Congenital diaphragmatic hernia;Consumption;cost;Cre driver;CRISPR/Cas technology;Data;Death Rate;Defect;Detection;Development;diagnostic tool;Embryo;embryo tissue;Etiology;exome;exome sequencing;Family member;Future;Gene Deletion;Gene Expression Profile;Gene Frequency;Gene Targeting;Generations;Genes;Genetic;Genetic Predisposition to Disease;genetic variant;Genome;genome editing;Genome Mappings;genome sequencing;genomic data;Germ Lines;Goals;Human;Image;improved;in silico;in vivo Model;Individual;Infant Mortality;insight;Knock-in;Level of Evidence;Live Birth;Longitudinal Studies;Lung;lung development;lung maturation;malformation;Mediating;microCT;migration;Modeling;Morphology;mouse model;Mus;Muscle;Mutagenesis;novel;Optics;Outcome;Pathology;Pathway Analysis;Patients;Phenotype;pulmonary function;Pulmonary Hypertension;pulmonary hypoplasia;Recurrence;Reproducibility;Reproductive Biology;Respiratory Diaphragm;Role;Sampling;Single Nucleotide Polymorphism;Speed;Structural Congenital Anomalies;Structure;Testing;therapeutic development;Time;transmission process;Validation;Variant;whole genome

PROJECT_TITLE: Functional Validation of Novel Variants Associated with Congenital Diaphragmatic Hernia

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Chronic Pain;Interstitial Cystitis;Neurosciences;Pain Research;Urologic Diseases

ORG_CITY: MILWAUKEE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: PROJECT NARRATIVE Millions of people are affected by benign bladder disorders, including overactive bladder, cystitis, recurrent urinary tract infection, and bladder pain syndrome that dramatically decrease quality of life. Urothelial cells, the cells that line the inside of the bladder, are thought to convey sensory and nociceptive information to the brain via sensory neurons, and urothelial cells and their signaling are often disrupted in these disorders. For these reasons, we plan to investigate the role of urothelial cells in sensory signaling and nociception using new innovative approaches.

PI_NAMEs: MICKLE, AARON DAVID (contact)

PROGRAM_OFFICER_NAME: MULLINS, CHRISTOPHER V

PROJECT_TERMS: Address;Affect;afferent nerve;Afferent Neurons;Animals;Area;awake;Behavior;Behavioral;Benign;Bladder;Bladder Diseases;bladder pain;Brain;Brain region;C Fiber;Cell Line;cell type;Cells;Central Nervous System;Chemicals;Chemoreceptors;Classification;Communication;Complex;Cystitis;Data;Devices;Disease;Distress;Electrophysiology (science);Epithelium;Esthesia;experimental study;flexibility;Functional disorder;Functional Magnetic Resonance Imaging;Goals;Histology;improved;Individual;Infective cystitis;Inflammatory;Injury;innovation;insight;Interoception;Interstitial Cystitis;Knowledge;knowledge base;Light;Maps;Methodology;Modeling;Molecular;mouse model;Mus;Nerve;Neurons;neurotransmission;Nociception;novel;optogenetics;Overactive Bladder;Pain;Pain Disorder;Pathologic;Pelvis;Persons;Pharmacology;Phenotype;Physiological;Physiology;Play;Population;Population Heterogeneity;Quality of life;Recurrence;Role;Sensory;Sensory Disorders;Signal Pathway;Signal Transduction;Stimulus;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;tool;Urinary tract infection;Urothelial Cell;Urothelium;Visceral;Visceral pain;wireless

PROJECT_TITLE: Urothelial Cells and Sensory Signaling

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Obesity;Physical Activity;Physical Rehabilitation;Prevention;Rehabilitation

PHR: Heart failure with preserved ejection fraction is common and causes severe shortness of breath with activity. Increasing physical activity improves patients’ symptoms, but most are sedentary. We propose a gamification intervention to increase physical activity and improve quality of life.

PI_NAMEs: FANAROFF, ALEXANDER CRAIG (contact)

PROGRAM_OFFICER_NAME: SHIROMA, ERIC JITSUO

PROJECT_TERMS: Activities of Daily Living;Address;Adherence;Adoption;arm;Atherosclerosis;atherosclerosis risk;Behavior Therapy;behavioral economics;Cardiomyopathies;Cities;Clinical;clinical practice;cohort;Computer software;cost;Data;Decision Making;design;Dyspnea;Economics;effectiveness evaluation;EFRAC;Elements;Exercise;exercise intensity;exercise intolerance;exercise training;Exertion;Family member;Fatigue;Feedback;follow-up;Friends;Funding;Guidelines;Health;Health behavior;Heart failure;Home;Hospitalization;Human;improved;Incentives;Individual;individual patient;innovation;insight;Intervention;Kansas;Label;Measures;Methods;National Heart, Lung, and Blood Institute;obese patients;obese person;older adult;Participant;Patients;Performance;pharmacologic;Physical activity;Population;post intervention;preservation;Prevalence;Psychology;Public Health;Quality of life;Questionnaires;Randomized, Controlled Trials;Recommendation;Reporting;Research Priority;sedentary;Self Direction;Shortness of Breath;social;social competition;Symptoms;Syndrome;Testing;Therapeutic;therapy design;Time;Translating;treatment arm;trial enrollment;United States National Institutes of Health;virtual;Walking;wearable device;working group

PROJECT_TITLE: A Randomized Controlled Trial of Gamification and Social Incentives to Increase Adherence to Physical Activity Among Patients with Heart Failure with Preserved Ejection Fraction

STUDY_SECTION: BMHO

STUDY_SECTION_NAME: Biobehavioral Medicine and Health Outcomes Study Section[BMHO]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Bipolar Disorder;Brain Disorders;Clinical Research;Data Science;Depression;Genetics;Health Services;Human Genome;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Serious Mental Illness;Social Determinants of Health

PHR: NARRATIVE The mission of the PsycheMERGE Network is to advance equitable precision psychiatry in learning healthcare system frameworks across the United States. During the course of this project, an interdisciplinary team of investigators at twelve academic medical centers will bring together clinical data (>29 million individuals), genetic data (>1.9 million), and an extraordinary range of scientific expertise (psychiatry, medical informatics, machine learning, statistics, genetics, sociomedical sciences, decision sciences, and ethics) to advance this mission. We will leverage this expertise and data to build on our prior success and address barriers to scalability, utility of genomic data, clinical application, and translation to clinical practice.

PI_NAMEs: BIERNACKA, JOANNA M (contact)

PROGRAM_OFFICER_NAME: MEINECKE, DOUGLAS L

PROJECT_TERMS: Academic Medical Centers;acceptability and feasibility;Acute;Address;algorithm training;Algorithms;anti-depressive agents;Artificial Intelligence;artificial intelligence method;Attitude;Awareness;Basic Science;Big Data;biobank;Biology;Biomedical Research;Bipolar Disorder;Bipolar I;causal variant;Clinical;clinical application;Clinical Data;clinical decision support;clinical practice;Communities;Country;Data;data privacy;depressive symptoms;Development;Diagnosis;Diagnostic;Differential Diagnosis;disability;Disease;Early Diagnosis;Early treatment;effective therapy;Effectiveness;Environment;Equity;Ethics;experience;federated learning;Funding;Genes;Genetic;genetic analysis;genetic association;genome wide association study;genome-wide;genomic data;Genomics;Goals;Grant;Health system;Healthcare Systems;improved;Individual;individual variation;Infrastructure;innovation;Label;large scale data;Learning;Left;Life Style;Machine Learning;machine learning algorithm;Maps;Medical;Medical Informatics;Medical Records;member;Mental disorders;Methods;Midwestern United States;Mission;Modeling;Mood Disorders;Morbidity - disease rate;mortality;National Institute of Mental Health;network models;novel;Outcome;Patients;Pattern;Performance;Phenotype;Population;precision medicine;predicting response;Prediction of Response to Therapy;Prevention;privacy preservation;Process;Psychiatric Diagnosis;Psychiatry;Records;Research Personnel;response;risk prediction;Sampling;Science;Scientist;Site;social health determinants;Standardization;statistics;Strategic Planning;success;support tools;Testing;Time;tool;Training;transfer learning;Translational Research;Translations;treatment response;United States;Update;Validation;Vision;Work

PROJECT_TITLE: 6/7 PsycheMERGE: Advancing Precision Psychiatry

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 EPH-D (65)]


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

ORG_DEPT: OTHER HEALTH PROFESSIONS

PHR: Many patients with blood cancers now take pills to control their cancer, but it can be difficult for patients to start these medications in a timely manner and to consistently take their pills as prescribed. The reasons for these difficulties, the patients who face the most barriers, and the effects that delays and inconsistent pill taking may have on patients’ health are not well known. This study describes how long it takes patients to start their cancer pills and how they take them over time; identifies barriers they may face; and how patients’ health may be affected by their ability to start and continue taking their cancer pills.

PI_NAMEs: BELCHER, SARAH M. (contact)

PROGRAM_OFFICER_NAME: CASTRO, KATHLEEN M

PROJECT_TERMS: Accounting;Adherence;Affect;African American;anti-cancer;Black race;cancer health disparity;cancer therapy;cancer type;Caring;Characteristics;Chronic Lymphocytic Leukemia;Chronic Myeloid Leukemia;Clinical;clinical predictors;clinically relevant;cost;Data;design;Development;Disparate;Dose;Drops;Drug Prescriptions;Employment;Equity;Ethnic Origin;experience;Future;Goals;Health;health care service utilization;health equity;Hematologic Neoplasms;Hematopoietic Neoplasms;Hispanic;improved;Individual;Infrastructure;Insurance;Intervention;Interview;Knowledge;Life;Malignant Neoplasms;Measures;medical specialties;medication administration;medication compliance;medication nonadherence;Methods;Molecular;mortality;Multiple Myeloma;National Institute on Minority Health and Health Disparities;Not Hispanic or Latino;novel;Oral;Oral Characters;Oral Examination;Outcome;Participant;Patient Self-Report;Patients;Pattern;Pharmaceutical Preparations;Pharmacy facility;Phase;pill;poor health outcome;Progression-Free Survivals;prospective;Quality of life;Race;Reporting;Research;Research Methodology;Research Personnel;response;Risk;Sampling;socioeconomics;standard of care;Structure;Symptom Burden;Symptoms;System;theories;therapy development;Time;treatment response;Work

PROJECT_TITLE: Identifying Multi-Level Predictors and Outcomes of Oral Anticancer Medication Adherence Initiation and Persistence among Patients with Hematologic Malignancies

STUDY_SECTION: CMGC

STUDY_SECTION_NAME: Clinical Management in General Care Settings Study Section[CMGC]


PHR: The mission of the PsycheMERGE Network is to advance equitable precision psychiatry in learning healthcare system frameworks across the United States. During the course of this project, an interdisciplinary team of investigators at twelve academic medical centers will bring together clinical data (>29 million individuals), genetic data (>1.9 million), and an extraordinary range of scientific expertise (psychiatry, medical informatics, machine learning, statistics, genetics, sociomedical sciences, decision sciences, and ethics) to advance this mission. We will leverage this expertise and data to build on our prior success and address barriers to scalability, utility of genomic data, clinical application, and translation to clinical practice.

PI_NAMEs: KEMBER, RACHEL LORRAINE (contact)

PROJECT_TITLE: 4/7-PsycheMERGE: Advancing Precision Psychiatry