NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because average years of life lost to pediatric sarcomas has remained unacceptably low and unchanged over the last three decades, with less than 30% overall survival in those with relapsed disease. Immunotherapy offers a potential alternative or synergistic approach to chemotherapy; at the conclusion of this study, we will understand if manipulating immune inhibitory signals in the tumor microenvironment using immune check point inhibition safely augments the clinical efficacy of chimeric antigen receptor T cells, and we will prospectively identify factors that improve patient selection and guide interventions. These findings will contribute to opening research avenues into both the feasibility and biology of combination immunotherapy approaches, akin to the historical emergence of multi-drug chemotherapy regimens to improve cancer outcomes.

PI_NAMEs: HEGDE, MEENAKSHI G (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Address;Adoptive Transfer;Adult;anti-PD1 antibodies;Antigen Targeting;Antigens;antitumor effect;Antitumor Response;Autologous;Biology;biomarker identification;CAR T cell therapy;CD19 gene;CD8B1 gene;Cell Line;cell mediated immune response;Cell Separation;Cell Therapy;Cells;checkpoint inhibition;chemotherapy;Chemotherapy-Oncologic Procedure;Child;childhood sarcoma;chimeric antigen receptor T cells;Clinic;Clinical;clinical efficacy;clinical predictors;Clinical Research;Clinical Trials;cohort;Combination immunotherapy;Cyclophosphamide;Data;design;Development;Disease;Dose;Down-Regulation;Engineering;ERBB2 gene;Event;fludarabine;Functional disorder;Future;Goals;Hematologic Neoplasms;Immune;immune cell infiltrate;immune checkpoint;immune checkpoint blockade;Immune checkpoint inhibitor;Immune signaling;Immunologic Markers;Immunotherapy;improved;In complete remission;Infusion procedures;innovation;Intervention;Investigational Drugs;Investigational New Drug Application;Kinetics;Knowledge;Literature;Malignant Neoplasms;novel strategies;Observational Study;Outcome;Patient Selection;Patients;PD-1 blockade;PD-1/PD-L1;peripheral blood;Pharmaceutical Preparations;Phase;phase 1 study;Phase I Clinical Trials;phase I trial;preclinical study;predictive marker;Predisposition;programmed cell death ligand 1;programmed cell death protein 1;Property;prospective;Public Health;rational design;receptor;Recurrence;Recurrent disease;Refractory;Relapse;Reporting;Research;research clinical testing;Research Personnel;response;Rhabdomyosarcoma;ROR1 gene;Safety;Sarcoma;Serum;Signal Transduction;Solid Neoplasm;success;T cell response;T-Cell Receptor;T-Lymphocyte;Testing;Therapeutic;Toxic effect;Transgenes;Treatment outcome;treatment response;tumor;Tumor Antigens;Tumor Escape;tumor microenvironment;Tumor Promotion;Tumor Tissue;Up-Regulation;years of life lost;young adult

PROJECT_TITLE: Modulating the PD-1/PD-L1 checkpoint to promote antitumor activity of HER2 CAR T cells in patients with sarcoma

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ADMINISTERING_IC: HD

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Contraception/Reproduction;Dissemination and Implementation Research;HIV/AIDS;Health Services;Infectious Diseases;Prevention;Primary Health Care;Women's Health Research

ORG_CITY: SEATTLE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Integrating HIV treatment and prevention into family planning clinics offers a promising approach to reach reproductive aged women, including the priority population of adolescent girls and young women, who may be otherwise missed in a siloed healthcare system. This study will provide necessary information regarding SAIA’s reach, effectiveness, adoption, implementation and maintenance in the real world setting when implemented at scale by Kenyan public health staff to increase HIV counseling, HIV testing, linkage to HIV care, and screening and linkage to PrEP as well as SAIA’s effect on the County budget. SAIA has the potential to dramatically improve women’s sexual and reproductive health by improving HIV prevention and treatment services for women in Kenyan family planning clinics.

PI_NAMEs: EASTMENT, MCKENNA CLAIRE (contact)

PROGRAM_OFFICER_NAME: DEYAMPERT, TARA LYNN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adopted;Adoption;Africa South of the Sahara;African Women;Age;aged;AIDS prevention;Area;budget impact;Budgets;Caring;Client;Clinic;Cluster randomized trial;compare effectiveness;comparison control;comparison intervention;Consolidated Framework for Implementation Research;cost;Counseling;County;Data;Dissemination and Implementation;Effectiveness;effectiveness evaluation;evidence base;experience;Family health status;Family Planning;Female Adolescents;Guidelines;Health;Health care facility;Health Personnel;Health Policy;Healthcare Systems;HIV;HIV Infections;Home;Hospitals;Human immunodeficiency virus test;Human Resources;implementation evaluation;implementation facilitators;implementation research;implementation science;implementation strategy;improved;Incidence;incremental cost;innovation;Intervention;Kenya;Logic;Maintenance;Maps;men;Modeling;NIH Office of AIDS Research;Oral;organizational readiness;Outcome;Persons;Policies;Politics;Population;Positioning Attribute;pre-exposure prophylaxis;Prevalence;Prevention;prevention service;Primary Care;Procedures;Process;programs;Public Health;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;reproductive;Research;Research Priority;scale up;screening;seropositive;Services;sexual and reproductive health;Southern Africa;Surveys;Systems Analysis;Testing;therapy development;Time;tool;treatment arm;treatment as prevention;treatment services;Universities;uptake;Washington;Woman;Women's study;Work;young woman

PROJECT_TITLE: Systems analysis and improvement approach to improve integration of HIV prevention and treatment services

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-RPHB-T(04)]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Eating Disorders;Mental Health;Mental Illness;Nutrition;Serious Mental Illness;Telehealth

ORG_CITY: PHILADELPHIA

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE Digital health technologies have high potential to promote between-session skill utilization and acquisition when used as a treatment augmentation to outpatient CBT for bulimia nervosa and binge eating disorder, yet little is known about which specific technological components may be needed to enhance skill utilization and acquisition and improve treatment outcomes. The proposed study will use a Multiphasic Optimization Strategy approach, including a full factorial design, in which 264 individuals with transdiagnostic binge eating pathology are assigned to one of six treatment conditions, i.e., representing each permutation of two promising digital health technological components that may enhance skill utilization and acquisition (e.g. self-monitoring complexity (Skills-Monitoring On vs. Skills-Monitoring Off) and micro-intervention complexity (No Micro- Interventions vs. Automated Reminder Messages vs. Just-in-Time Adaptive Interventions)) when used as an augmentation to outpatient CBT. Results of the component analysis set up future work to evaluate an optimized digital health tool containing only effective components (which can be expected to have superior target engagement, efficacy, efficiency and disseminability) and will identify key moderators of treatment outcome to facilitate treatment matching.

PI_NAMEs: MANASSE, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: BURSTEIN, MARCY ELLEN

PROJECT_TERMS: acceptability and feasibility;adaptive intervention;Aftercare;Algorithms;Attention;Behavior;Binge Eating;Binge eating disorder;Bulimia;Clinical;Clinical Trials;Cognitive;cognitive benefits;Cognitive Therapy;comparison intervention;cost;Data;data sharing;design;Diagnostic;digital;digital health;digital intervention;discrete time;Disease remission;Eating;Eating Disorders;eating pathology;effective therapy;Emotional;experience;feasibility testing;follow-up;Food;Frequencies;Future;Goals;Health Technology;improved;Impulsivity;Individual;Informal Social Control;Intervention;Learning Skill;loss of control over eating;Machine Learning;Methods;Modality;Monitor;multiphase optimization strategy;National Institute of Mental Health;Outcome;Outpatients;Participant;participant interview;Pathway interactions;patient subsets;Patients;Persons;pilot trial;Randomized;Research;Research Priority;skill acquisition;skills;Symptoms;System;Technology;Testing;Therapeutic;Time;tool;Treatment outcome;Work

PROJECT_TITLE: Optimizing digital health technologies to improve therapeutic skill use and acquisition


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Natural Products

ORG_CITY: TALLAHASSEE

ORG_DEPT: CHEMISTRY

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: PROJECT NARRITIVE The proposed research is relevant to public health because it focuses on the chemistry and biology of terpenoids with impactful pharmacological profiles. The objective of this proposal is to use these complex natural products as a starting point to develop prototype chemotherapeutics for cancer. For this reason, the proposed research is relevant to the NIH’s mission of developing fundamental knowledge that enhances human health.

PI_NAMEs: FREDERICH, JAMES H. (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: 3-hydroxy-3-methylglutaryl-coenzyme A;Address;Apoptosis;Apoptotic;Award;Binding;Biochemical;Biochemistry;Biological;Biology;cancer therapy;Cell Culture Techniques;Cell membrane;Cellular biology;Chemicals;Chemistry;Coenzyme A;Collaborations;Complex;cytotoxic;Cytotoxin;Data;design;Disease;drug discovery;Epitopes;Exhibits;Family;Family member;FDA approved;fungus;fusicoccin;Grant;Health;Human;Individual;inhibitor;innovation;Isomerism;Knowledge;lens;Malignant Neoplasms;Mediator;Medicine;member;Membrane;Methods;Mission;Modification;Molecular;Molecular Conformation;molecular shape;Natural Products;Nature;novel therapeutics;ophiobolins;Organism;Oxidoreductase;Pathway interactions;Peripheral;Pharmaceutical Preparations;pharmacologic;Pharmacology;Property;protein protein interaction;prototype;Public Health;receptor;Reporting;Research;Route;scaffold;Serine;sesterterpenes;skeletal;Specificity;structural determinants;Structure;sugar;Synthesis Chemistry;System;Terpenes;Testing;Therapeutic;tool;translational potential;United States National Institutes of Health;Work

PROJECT_TITLE: A Divergent Platform to Chemically Redesign Bioactive 5-8-5 Terpenoids

STUDY_SECTION: SBCA

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Food Allergies

ORG_CITY: INDIANAPOLIS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: We have discovered a new T cell subset, TFH-IgE cells, that are a key regulator of the allergic immune response and IgE, but much is unknown about how these cells are regulated. These studies will find pathways that control TFH-IgE cells and may lead to new therapies for the treatment of allergic diseases such as asthma and food allergy.

PI_NAMEs: DENT, ALEXANDER L (contact)

PROGRAM_OFFICER_NAME: LIN, ADORA ASHELY

PROJECT_TERMS: Adjuvant;Affinity;Allergens;Allergic;allergic airway inflammation;Allergic Disease;allergic response;Anaphylaxis;Antibodies;Antibody Affinity;Antigens;Asthma;B-Lymphocytes;Bone Marrow;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Chimera organism;Clonal Expansion;cost;Data;Development;Food Hypersensitivity;Gene Expression;Germ Lines;Glucocorticoids;Goals;Healthcare;Helper-Inducer T-Lymphocyte;human disease;IgE;IL4 gene;Immediate hypersensitivity;Immune response;inhibitor;insight;Interleukin-2;Interleukin-4;Knockout Mice;Life;Light;Literature;Mediator;Methods;Modeling;Mus;novel;novel therapeutics;Pathway interactions;Phase;Production;Productivity;Proteins;Quality of life;Reaction;Regulation;Regulator Genes;response;Role;Signal Pathway;Signal Transduction;Structure of germinal center of lymph node;System;T-Lymphocyte;T-Lymphocyte Subsets;targeted treatment;Testing;Th2 Cells;TNFSF5 gene;United States;Work

PROJECT_TITLE: TFH cell programming for IgE responses

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDB-K(57)]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

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

ORG_CITY: EUGENE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: NARRATIVE Tissues and organs are comprised of many different types of cells which are all made from stem cells. Failure to make the proper number of cells can cause disease. The goal of this project is to understand how stem cells produce the correct number of cells, in the hopes that this understanding can lead to new disease treatments.

PI_NAMEs: LAFOYA, BRYCE  (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: Animal Model;Animals;Apical;Biological Assay;Brain;cell cortex;Cell Cycle;Cell division;Cell Lineage;Cell Proliferation;cell type;Cells;Central Nervous System;Data;Daughter;daughter cell;Defect;Development;Disease;Drosophila genus;Educational process of instructing;Ensure;Failure;follow-up;Goals;Grant;Growth;improved;Inherited;Invertebrates;Laboratories;Learning;Lipids;live cell imaging;Measures;Mediating;member;Mentors;Modeling;Molecular;Mothers;nerve stem cell;neurogenesis;Neurons;Organ;Pathway interactions;PIK3CG gene;prevent;programs;Proliferating;Proliferation Marker;Proteins;Regulation;repaired;Research;Role;Running;S-Phase Fraction;screening;segregation;Siblings;Side;skills;Specific qualifier value;stem cell division;stem cell proliferation;stem cell therapy;stem cells;System;Testing;tissue repair;Tissues;Training;Training Activity;training opportunity;tumorigenesis;Vertebrates;Work;Writing;Zebrafish

PROJECT_TITLE: Proliferative asymmetry in the neural stem cell lineage established by asymmetric cell division


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Sleep Research;Social Determinants of Health

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: NARRATIVE African American adults sleep less and obtain worse quality sleep compared to the national average, and emerging evidence links inadequate sleep with morbidity and mortality from chronic diseases such as diabetes, obesity, and cancer. To address this public health concern, the proposed research seeks to understand social contextual factors related to sleep and obesity by using a multi-method approach, and to use the knowledge gained to adapt a sleep intervention for overweight, sedentary, and chronically sleep-deprived African Ameri- can adults. The goal of the project is to understand how the social context impacts sleep and obesity to reduce cancer-related health disparities among African Americans.

PI_NAMEs: WU, IVAN H (contact)

PROGRAM_OFFICER_NAME: STINSON, NATHANIEL

PROJECT_TERMS: Address;Adult;Affect;African American;African American population;African American Women;American Cancer Society;Behavior;Belief;Body mass index;Body Weight;burden of illness;cancer health disparity;Chronic;Chronic Disease;Church;Clinical;Clinical Trials Design;cohort;Communities;Conflict (Psychology);contextual factors;culturally appropriate intervention;Data;Data Analytics;Data Set;Dedications;design;Development;Diabetes Mellitus;Diagnosis;Diet;Disadvantaged;Disease;disparities in morbidity;Disparity;disparity gap;Educational workshop;energy balance;ethnic minority;ethnic minority population;experience;Exposure to;Faith;Family;Fatigue;feasibility testing;Feedback;Goals;Health;Health behavior;Health Campaign;health disparity;healthy lifestyle;improved;improvement on sleep;Individual;innovation;Institutional Review Boards;Intervention;Interview;Knowledge;lectures;Link;Malignant Neoplasms;Mediating;Medicine;member;men;Mentors;Methods;Minority Groups;Morbidity - disease rate;mortality;mortality disparity;National Institute on Minority Health and Health Disparities;neighborhood disadvantage;Neighborhoods;Obesity;Obesity associated cancer;obesity risk;obesity treatment;Overweight;Pathway interactions;Perception;Phase;Physical activity;poor sleep;Positioning Attribute;protective factors;Protocols documentation;psychologic;Psychologist;Public Health;racial minority;racial minority population;racial population;Recommendation;Reporting;Research;Research Methodology;Research Personnel;Research Priority;Risk;Risk Factors;Role;Sample Size;Sampling;satisfaction;sedentary;sedentary lifestyle;Sleep;Sleep Deprivation;Sleep disturbances;sleep quality;Sleeplessness;social determinants;Social Environment;Social support;Spirituality;Stress;Testing;Training;trend;University of Texas M D Anderson Cancer Center;Work

PROJECT_TITLE: Social determinants of sleep and obesity: Disparities in African Americans


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cardiovascular

ORG_CITY: SAN FRANCISCO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Dysregulation of vascular barrier function, the selectively permeable barrier established by endothelial cells that line blood vessels to regulate the exchange of fluids, cells, and nutrients, contributes to a variety of cardiovascular, inflammatory, and neurodegenerative diseases. Despite a critical clinical demand, we lack interventional strategies to repair or modulate vascular barrier, largely due to a poor understanding of the master regulators within the vascular endothelium. This proposal aims to reveal new mechanisms of how the Notch1 receptor activates under shear stress, increasing barrier function, and potentially identify new therapeutic targets for modulating barrier function and other vasculopathies where Notch1 is implicated.

PI_NAMEs: SINGH, TANIA  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: 3-Dimensional;Ablation;Actins;Adherens Junction;Adhesives;Architecture;Atherosclerosis;Barbering;beta catenin;Binding;Biomimetics;Biosensor;Blocking Antibodies;Blood;Blood Circulation;Blood flow;Blood Plasma Volume;Blood Vessels;C-terminal;cadherin 5;Cardiovascular Diseases;career;career development;Cell Adhesion Molecules;Cell Line;Cell membrane;Cell-Cell Adhesion;Cells;Chronic;Clathrin;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Communication;Complex;Coupling;Cytoskeleton;Data;Disease;Edema;Educational process of instructing;Endothelial Cells;endothelial dysfunction;Endothelium;Equilibrium;experience;Family;Friction;Genetic Transcription;Goals;hemodynamics;Homeostasis;Human;Human Development;human model;improved;Inflammatory;inhibitor;insight;Intervention;Ischemia;Knowledge;Lead;Ligands;Link;Liquid substance;live cell microscopy;Measures;mechanical force;Mechanics;Mediating;Mentors;Modeling;Molecular;Morphogenesis;mutant;Myocardial Infarction;Natural regeneration;Neurodegenerative Disorders;new therapeutic target;notch protein;novel;Nutrient;Pathogenesis;Pathologic;Pathway interactions;Permeability;Phosphorylation;polymerization;Polymers;prevent;Process;Proteins;Proteomics;receptor;Receptor Activation;Regulation;repaired;Research;Resistance;response;Role;sensor;shear stress;Signal Transduction;spatiotemporal;Stroke;superresolution microscopy;Testing;Tissue Model;Tissues;Training;Transducers;ultra high resolution;Vascular Cell Adhesion Molecule-1;Vascular Diseases;Vascular Endothelium;Vascular Permeabilities;Work

PROJECT_TITLE: Shear stress-mediated Notch1 activation by intrinsic cell adhesive and cytoskeletal activity


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Pediatric;Rare Diseases

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE Craniofacial microsomia is one of the most common birth defects that affects the face. We have identified a gene, Foxi3, that can cause craniofacial microsomia in both humans and mice. We will use mouse genetics to test the contributions of Foxi3 to craniofacial microsomia, and we will create models of human Foxi3 mutations in mice to understand the signals that are disrupted during fetal development in individuals with these birth defects.

PI_NAMEs: GROVES, ANDREW K (contact)

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: Address;Affect;Alleles;Animal Model;Binding;Bioinformatics;Biological Assay;Branchial arch structure;Cells;Cephalic;Chromatin;Cleavage Under Targets and Release Using Nuclease;cleft lip and palate;Cleft lip with or without cleft palate;Complex;conditional mutant;Congenital Abnormality;craniofacial;Craniofacial Abnormalities;craniofacial development;craniofacial microsomia;Craniosynostosis;Data;Defect;Dermoid Cyst;Development;Disease;disease model;Ear ossicles;Ectoderm;Embryo;Endoderm;Exhibits;External Ear;Face;Facial asymmetry;Family;Fetal Development;First Pharyngeal Arch;GATA3 gene;Gene Expression;Gene Expression Profiling;gene interaction;gene regulatory network;Genes;Genetic;genetic disorder diagnosis;Genetic Transcription;genetic variant;genome wide association study;Goldenhar Syndrome;Health;Heterogeneity;Heterozygote;Human;human model;Individual;Individuation;Inherited;insight;Jaw;Knockout Mice;Live Birth;Mandible;member;microtia;middle ear;migration;Modeling;Molecular;Morphology;mouse genetics;mouse model;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;Neural Crest;Neural Crest Cell;Pathogenicity;Patients;Pattern;Pharyngeal pouch;Pharyngeal structure;Phenotype;Role;Second branchial arch structure;Series;Severities;Side;Signal Transduction;single-cell RNA sequencing;spine bone structure;Symptoms;Testing;Time;Tissues;Toxic Environmental Substances;transcription factor;Variant;virulence gene;Wild Type Mouse

PROJECT_TITLE: The role of the Foxi3 transcription factor in craniofacial microsomia

STUDY_SECTION: SBDD

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


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breast Cancer;Cancer;Digestive Diseases;Immunization;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Narrative Pancreatic ductal adenocarcinoma continues to be one of most deadly malignant diseases due to the tumor’s highly immunosuppressive nature. In this proposal we seek to engineer dual-target binding antibodies that can preferentially bind pancreatic cancer cells and inhibit immunosuppressive molecules within the tumor, while also better engaging immune cells to eliminate the pancreatic cancer cells. If successful, our work may introduce a promising therapeutic strategy for improved treatment of pancreatic cancer.

PI_NAMEs: LAI, SAMUEL  (contact)

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: Abbreviations;Affinity;Agreement;Animals;Antibodies;Avidity;B-Lymphocytes;bi-specific T cell engager;Binding;bioprocess;Bispecific Antibodies;Bite;C57BL/6 Mouse;Cancer Etiology;CD3 Antigens;CD8-Positive T-Lymphocytes;Cells;Cessation of life;Characteristics;chemotherapy;CTLA4 gene;CXCL13 gene;cytokine;Data;Death Rate;design;Disease;Dose;Drug Delivery Systems;effective therapy;Effectiveness;Engineering;Epithelial Cells;Fab domain;Goals;Growth;Human;Image;Immune;Immune checkpoint inhibitor;Immune Evasion;Immunocompetent;Immunoglobulin G;Immunoglobulin M;Immunosuppression;Immunosuppressive Agents;Immunotherapy;improved;Infiltration;knock-down;Lead;Leukocytes;Light;luminescence;Macrophage;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Mammary Neoplasms;Measures;Mediating;Melanoma Tumor;Mesenchymal;Modeling;Molecular;monocyte;mouse model;Mus;Myeloid Cells;Myeloid-derived suppressor cells;nanomedicine;Nature;nuclear factors of activated T-cells;overexpression;Pancreas;pancreatic cancer cells;pancreatic cancer model;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic neoplasm;Patients;Peripheral Blood Mononuclear Cell;Pilot Projects;Production;programmed cell death ligand 1;Publications;Regulatory T-Lymphocyte;Resistance;response;safety assessment;Signal Transduction;Stromal Cells;subcutaneous;Suppressor-Effector T-Lymphocytes;Survival Rate;T cell response;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Therapeutic;Toxic effect;Transforming Growth Factor beta;triple-negative invasive breast carcinoma;tumor;Tumor Cell Migration;tumor growth;tumor microenvironment;Tumor Promotion;Tumor Suppression;Tumor-associated macrophages;tumor-immune system interactions;Vascularization;Work;Xenograft Model

PROJECT_TITLE: Engineering Siglec15/TGF-beta targeted bispecific antibodies that modulate the tumor microenvironment and enhances T-cell immunotherapy against pancreatic cancer


NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Orphan Drug;Prevention;Radiation Oncology;Rare Diseases

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

ORG_STATE: MO

PHR: Narrative Ionizing radiation (IR) therapy for head and neck squamous cell carcinoma (HNSCC) frequently results in salivary gland dysfunction and xerotomia that leads to mucositis, dental caries, malnutrition and overall decreased quality of life. The primary goals of this study are to determine whether and how inhibition of the P2X7 receptor (P2X7R) can protect the salivary gland from IR-induced dysfunction without having a deleterious effect on IR therapy for HNSCC. Results of these studies will be a major step towards validating a P2X7R-targeted therapy for preventing IR-induced salivary gland damage in humans.

PI_NAMEs: WEISMAN, GARY ANDREW (contact)

PROGRAM_OFFICER_NAME: CHANDER, PREETHI

PROJECT_TERMS: Acceleration;Acute;Adenosine;antagonist;Antitumor Response;Apoptosis;cancer therapy;CASP3 gene;Cations;cell injury;cell type;Cells;Chronic;Cytoplasm;Cytoskeleton;Dental caries;Dinoprostone;Dose;Epithelium;Exhibits;extracellular;Functional disorder;Genetic;Goals;Head and Neck Cancer;head and neck cancer patient;Head and Neck Squamous Cell Carcinoma;Human;Human Cell Line;Immune;in vivo;Individual;Inflammasome;Inflammatory;innovation;Interleukin-1 beta;Ionizing radiation;irradiation;Kinetics;Knowledge;Malnutrition;Mediating;Morphology;mouse model;mouth squamous cell carcinoma;Mucositis;Mus;neoplastic cell;Normal tissue morphology;novel;novel strategies;nucleotide receptor;Nucleotides;Output;Patients;pharmacologic;preservation;prevent;Prevention;Production;Purinergic P1 Receptors;Quality of life;Radiation;Radiation Protection;Radiation therapy;Radiation-Induced Cancer;Radiation-Protective Agents;radioprotected;Reactive Oxygen Species;receptor;Receptor Activation;Regimen;response;Salivary;Salivary Glands;Sialadenitis;Signal Transduction;Site;targeted treatment;Technology;Testing;Therapeutic;therapeutic target;Time;Tissues;transcriptome;transcriptomics;Translating;Translations;Treatment Protocols;tripolyphosphate;tumor;tumor growth;Xerostomia

PROJECT_TITLE: The P2X7 receptor for ATP as a therapeutic target in the prevention of radiation-induced salivary gland dysfunction


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Infectious Diseases;Maternal Health;Pediatric;Pregnancy;Prevention;Social Determinants of Health;Vaccine Related;Women's Health Research

ORG_NAME: UNIVERSITY OF SAN FRANCISCO

PHR: PROJECT NARRATIVE Although pregnant persons are at higher risk of severe COVID-19 infection, there is currently limited data to inform COVID-19 immunization policies for this population group. Drawing from national, linked health information for over 870,000 mother-infant pairs, this research will provide large-scale evidence on the uptake, safety and effectiveness of maternal COVID-19 vaccination in terms of perinatal, neonatal and infant health outcomes. Completion of this research will facilitate informed decision-making among pregnant persons, those planning pregnancy and their healthcare providers.

PI_NAMEs: REGAN, ANNETTE KARENA (contact)

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TERMS: 2019-nCoV;Admission activity;adverse outcome;adverse pregnancy outcome;Advisory Committees;Age;American College of Obstetricians and Gynecologists;Anxiety;care providers;Centers for Disease Control and Prevention (U.S.);Cessation of life;Clinical;Clinical Trials;Cohort Studies;Computerized Medical Record;COVID-19;COVID-19 diagnosis;COVID-19 impact;COVID-19 vaccination;COVID-19 vaccine;Data;Databases;Decision Making;Discipline of obstetrics;Disease;Effectiveness;Electronic Health Record;Eligibility Determination;Emergency Situation;Ensure;Epidemiology;Event;Exclusion;experience;FDA Emergency Use Authorization;fetal;Fetal health;Goals;Guidelines;Health;Health Personnel;high risk;Immunization;implementation evaluation;Individual;Infant;Infant Health;Infection;influenza virus vaccine;Intensive Care;Intention;interest;Learning;Link;Maternal Health;maternal outcome;Mechanical ventilation;Medical;Mothers;Nature;neonatal health;neonatal outcome;neonate;new technology;Observational Study;Outcome;Participant;Passive Immunity;Perinatal;Perinatal mortality demographics;Persons;Phase;Phase II/III Clinical Trial;Phase III Clinical Trials;Planned Pregnancy;Policies;policy implication;Policy Making;policy recommendation;Population;Population Group;post implementation;post SARS-CoV-2 infection;Pregnancy;Pregnancy loss;pregnant;Premature Birth;prevent;Probability;programs;Public Health;Recommendation;Reporting;reproductive;Research;Risk;Risk Factors;Safety;SARS-CoV-2 exposure;SARS-CoV-2 infection;severe COVID-19;sociodemographics;Special Event;Surveys;System;systematic review;Time;unvaccinated;Update;uptake;Vaccinated;Vaccination;vaccination outcome;vaccination strategy;vaccine acceptance;vaccine safety;Vaccines;variants of concern;Woman

PROJECT_TITLE: Uptake, Safety and Effectiveness of COVID‐19 Vaccines during Pregnancy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-N(90)]


ADMINISTERING_IC: AR

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: NEW YORK

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

ORG_STATE: NY

PHR: PROJECT NARRATIVE The proposed new pre-doctoral Integrated Musculoskeletal Training Program aims to provide a unique and timely opportunity to promote, enhance, and deepen multidisciplinary musculoskeletal research by supporting trainees with the skills and the values needed to enter the diverse biomedical research workforce and to solve the complex problems of musculoskeletal disease in the future.

PI_NAMEs: CHAHINE, NADEEN O.;GUO, X. EDWARD (contact)

PROGRAM_OFFICER_NAME: VINCENT, ISAAH S

PROJECT_TERMS: Musculoskeletal;Training Programs


NIH_SPENDING_CATS: Complementary and Integrative Health;Congenital Structural Anomalies;Dietary Supplements;Genetics;Neurosciences;Nutrition;Pediatric;Prevention;Rare Diseases;Spina Bifida

ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: NARRATIVE Neural tube defects are the second most common birth defect leading to fetal mortality or life-long complications. The risk for developing a neural tube defect can be reduced by increasing folic acid in the diet of pregnant people in some cases, however we cannot predict who this preventative strategy is most beneficial for. The objective of this proposal is to provide insight into how folic acid can support neural tube closure to better inform risk assessment of neural tube defects.

PI_NAMEs: KAKEBEEN, ANNEKE D (contact)

PROGRAM_OFFICER_NAME: KOSTER, MARANKE IRENE

PROJECT_TERMS: Address;Affect;Articulation;Back;Bioinformatics;Brain;Candidate Disease Gene;candidate validation;cell behavior;cell fixing;cell motility;Cell Physiology;cell type;Cells;cellular imaging;Chick;Chick Embryo;Chromatin;Clinical;Collaborations;Communication;Communities;Compensation;Complex;Congenital Abnormality;Congenital Disorders;Data Analyses;Data Set;de novo mutation;Deposition;design;Development;Diet;Dimensions;Disease;Educational process of instructing;Embryo;Embryology;Environmental Risk Factor;environmental stressor;Etiology;experimental study;Extracellular Matrix;Failure;Family;Fetal Mortality Statistics;Folic Acid;Folic acid fortification;folic acid supplementation;Fortification;gene discovery;gene environment interaction;Gene Expression;Gene Expression Profile;Gene Mutation;gene regulatory network;Genes;Genetic;genetic testing;Genetic Transcription;high risk;Histological Techniques;Histology;Human;Image;improved;Incidence;information model;innovation;insight;Knock-out;Lead;Learning;meetings;Mentors;Mentorship;Modeling;Molecular;Morphogenesis;mouse genetics;Movement;Multiomic Data;Mus;mutant;mutant mouse model;Mutant Strains Mice;Neural tube;Neural Tube Closure;Neural Tube Defects;null mutation;Pattern;Persons;Play;Population;Pregnancy;pregnant;prenatal;Preparation;prevent;Prevention;Prevention strategy;Process;provider communication;Public Health;Research;Research Personnel;Risk;Risk Assessment;risk variant;screening;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;skills;Spinal Cord;Students;System;teacher;Techniques;Testing;Training;transcription factor;undergraduate research;undergraduate research experience;undergraduate student;United States;Validation;Work

PROJECT_TITLE: Uncovering the cellular and molecular mechanisms of folic acid fortification in neural tube defects

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-Q(20)L]


NIH_SPENDING_CATS: Cancer;Hematology;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Myelofibrosis (MF) is a devastating blood disorder. Current therapies are not sufficient to effectively treat MF. Therefore, there is an unmet critical need for new therapies for MF. In this study, we will investigate the effectiveness of pharmacological inhibition of IL-1 signaling in pre-clinical models of myelofibrosis. Results from this study may lead to new therapeutic approach for myelofibrosis.

PI_NAMEs: MOHI, GOLAM  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: Acute Myelocytic Leukemia;anakinra;Antibodies;Applications Grants;Binding;Bone Marrow;Bone Marrow Cells;calreticulin;Cell Lineage;Cells;chemotherapy;Chronic;Clonal Expansion;Clonal Hematopoietic Stem Cell;Collagen;Constitutional Symptom;cytokine;Data;Development;Disease remission;Drug Combinations;Effectiveness;effectiveness testing;efficacy testing;Exhibits;expectation;Genes;Genetic;Goals;Hematologic Neoplasms;Hematological Disease;Hematopoietic;Hematopoietic stem cells;Hemorrhagic Thrombocythemia;Heterozygote;Human;improved;Inflammation;inhibitor;Interleukin-1;Interleukin-1 Receptors;JAK2 gene;knock-down;Knock-in;Knock-in Mouse;MAP Kinase Gene;Mediating;mesenchymal stromal cell;Modeling;Molecular;mouse model;MPL gene;Mus;mutant;Mutation;Myelofibrosis;Myelogenous;Myeloid Cells;Myeloproliferative disease;new therapeutic target;novel strategies;novel therapeutic intervention;novel therapeutics;Oncogenic;p38 Mitogen Activated Protein Kinase;Pathogenesis;Pathway interactions;Patients;Penetrance;peripheral blood;pharmacologic;Play;Polycythemia Vera;Pre-Clinical Model;prevent;Production;Prognosis;Role;Signal Transduction;small hairpin RNA;Splenomegaly;Testing;Time;transcriptome sequencing;treatment effect;Treatment Failure;treatment strategy;Work

PROJECT_TITLE: Targeting of IL-1 Signaling in Myelofibrosis


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

PHR: Excess deaths have occurred during the coronavirus disease 2019 (COVID-19) pandemic, most commonly due to heart disease and particularly among vulnerable populations, raising the possibility of suboptimal healthcare utilization or quality of care. Accordingly, we propose an observational, retrospective, national cohort study of Veterans with cardiovascular disease. We will compare potential decreases in cardiovascular healthcare utilization and quality of care and an increase in mortality to that which occurred prior to the pandemic with a focus on vulnerable populations. We will then assess whether the changes in healthcare utilization and quality of care were associated with an increased risk of mortality. A stakeholder advisory panel led by VA operational leaders, investigators, and Veterans, will then be convened to develop recommendations and guide VA policies in the late- and/or post-pandemic period.

PI_NAMEs: HESS, PAUL LAURENCE;WALDO, STEPHEN  (contact)

PROJECT_TERMS: Acute myocardial infarction;Admission activity;adverse outcome;Age;Ambulatory Care Facilities;Atrial Fibrillation;Cardiology;Cardiovascular Diseases;cardiovascular health;Cardiovascular system;care delivery;Caring;Cessation of life;Clinic Visits;Clinical;Clinical assessments;clinical risk;cohort;Cohort Studies;Consensus;Coronary;Coronary Arteriosclerosis;COVID-19;COVID-19 pandemic;COVID-19 pandemic effects;Data;Data Sources;data warehouse;Death Rate;Diagnosis;Diagnostic tests;Discipline;Ensure;Equity;Ethnic Origin;Evaluation;evidence base;Federal Government;follow-up;Future;Gender;Guidelines;health care delivery;health care quality;health care service utilization;health equity;Health Personnel;Healthcare;Healthcare Systems;Heart Diseases;Heart failure;Hospitalization;Hospitals;improved;improved outcome;inpatient service;Inpatients;Integrated Health Care Systems;International;Investigation;Mediation;medical specialties;Methodology;Modeling;mortality;mortality risk;Outcome;Outpatients;pandemic disease;pandemic potential;Patient Admission;patient safety;Patients;percutaneous coronary intervention;Pharmaceutical Preparations;Policies;post-COVID-19;post-pandemic;pre-pandemic;Principal Investigator;Procedures;Process;Professional Organizations;programs;Quality of Care;Race;racial difference;Recommendation;Reporting;Research;research clinical testing;Research Personnel;Resources;revascularization;Sample Size;sex;Standardization;Subgroup;System;Time;tool;United States;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Virus;Vulnerable Populations;Work

PROJECT_TITLE: Impact of the Coronavirus Disease 2019 Pandemic on Cardiovascular HealthcareUtilization, Quality of Care, and Clinical Outcomes

STUDY_SECTION_NAME: HSR-5 Health Care System Organization and Delivery and Women's Health[HSR5]


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

PHR: Improving the quality, safety, and outcomes for our patients along with increasing bed availability and surge capacity in our hospitals while decreasing costs all fulfill the VA mission.

PI_NAMEs: BARRETT, THOMAS WILLIAM (contact)

PROJECT_TERMS: Adrenergic beta-Antagonists;Adverse drug event;Affect;Anaphylaxis;Anesthetics;Angiotensin Receptor;Angiotensin-Converting Enzyme Inhibitors;Anti-emetics;Antibiotics;Anticoagulants;Antidotes;Artificial Intelligence;artificial neural network;Aspirin;Bacteremia;Beds;Blood Vessels;Cardiac;Cardiac Surgery procedures;Cardiovascular system;Caring;Cessation of life;Characteristics;classification trees;Clinical;clinical care;clinical decision support;clinical practice;clopidogrel;Collaborations;cost;cost effectiveness;Cox Proportional Hazards Models;Cytochrome P450;Data;data warehouse;Databases;Decision Making;Delirium;design;drug metabolism;Drug Targeting;Drug Transport;Drug usage;Environment;Event;Exposure to;Frequencies;functional status;Future;Genes;Goals;Heart failure;Hemorrhage;Heparin;high risk;Home;hospital readmission;Hospitals;Immune response;Immunotherapeutic agent;improved;improved outcome;Individual;Informatics;Infrastructure;Injury to Kidney;innovation;Intervention;Intervention Studies;kidney dysfunction;Label;Learning;Length;Length of Stay;Life;Linear Regressions;Liver Dysfunction;liver injury;Machine Learning;machine learning method;Malignant hyperpyrexia due to anesthesia;Medicine;Metabolism;Methodology;Mission;Modeling;Myocardial Infarction;Naloxone;Non-Steroidal Anti-Inflammatory Agents;novel therapeutics;Operative Surgical Procedures;Opioid;opioid exposure;Oral;Outcome;pain score;Patient Care;patient oriented;patient subsets;Patients;performance site;Perioperative;Persons;Pharmaceutical Preparations;Pharmacogenomics;phenomics;phenotypic data;Pneumonia;Postoperative Pain;Postoperative Period;Private Sector;Procedures;process improvement;programs;prospective;Reaction;regression trees;Research;Resources;Retrospective cohort study;Risk;risk prediction;Safety;Sepsis;Single Nucleotide Polymorphism;Stroke;Subgroup;surgery outcome;surgical risk;Testing;thrombotic;Time;Treatment Effectiveness;treatment response;Update;Urinary tract infection;Variant;Venous;Veterans;Vitamin K;Warfarin;Wound Infection

PROJECT_TITLE: Precision Pharmacogenomic Perioperative Prediction

STUDY_SECTION_NAME: HSR-3 Healthcare Informatics[HSR3]


ORG_CITY: PITTSBURGH

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative: Transplantation is in critical need of improved therapeutics to enhance long-term graft survival. New knowledge reveals a previously underappreciated role of innate immune cells in transplant rejection, which are poorly controlled using current immunosuppressive regimens. These studies promise to discover novel nanotherapeutic drugs aiming at blocking innate immune cells and greatly improving long-term graft survival.

PI_NAMEs: CAMIRAND, GEOFFREY  (contact)

PROGRAM_OFFICER_NAME: NABAVI, NASRIN N

PROJECT_TERMS: Affect;allograft rejection;Allografting;Applications Grants;Calcineurin;Calcineurin inhibitor;Cell Physiology;Cells;Chronic;Data;effector T cell;Environment;Epigenetic Process;experimental study;FOXP3 gene;Genetic;genetic approach;Graft Rejection;Graft Survival;Grant;Homeostasis;Homologous Transplantation;Human;Immune;Immunity;Immunobiology;Immunologic Memory;immunoregulation;Immunosuppressive Agents;improved;Infiltration;Inflammation;intravital imaging;intravital microscopy;ITGAX gene;Knowledge;Molecular Target;mTOR Inhibitor;multi-photon;Mus;Myelogenous;nanobiologic;nanoparticle;nanotherapeutic;novel;nuclear factors of activated T-cells;Pathway interactions;Pharmaceutical Preparations;Phenotype;Positioning Attribute;prevent;Process;receptor;Regimen;Regulatory T-Lymphocyte;Role;Science;Signal Transduction;stem;success;targeted treatment;Technology;Testing;Therapeutic;therapeutic target;Time;Training;Transplantation;Visualization

PROJECT_TITLE: Promoting and Visualizing Immune Regulation in Transplantation


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Liver Disease;Obesity;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Non-alcoholic fatty liver disease (NAFLD), caused by excess accumulation of fat in the liver (steatosis), has a global prevalence of 25.2% and is the most common cause of chronic liver disease worldwide. The objective of this application is to identify additional rare variants with effects on NAFLD through whole genome sequencing (WGS) in ethnically diverse populations. In addition, CRISPR/Cas9 will be used to test genes for loss of function effects on hepatic steatosis. Results from our work will help us to understand the genetic architecture of NAFLD and link these associations to genes that can be targeted for therapeutic intervention.

PI_NAMEs: ALLRED, NICHOLETTE D. (contact);SPELIOTES, ELIZABETH K

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Affect;African;African ancestry;Alleles;attenuation;Biological;causal variant;Cell Line;Cells;chronic liver disease;clinical practice;cohort;cost;CRISPR screen;CRISPR/Cas technology;Data;Diagnosis;Disease;ethnic diversity;Ethnic Origin;Ethnic Population;Etiology;European;European ancestry;Fatty acid glycerol esters;Fatty Liver;follow-up;Functional disorder;Gene Frequency;Genes;Genetic;genetic architecture;genome sequencing;genome wide association study;genome wide screen;genome-wide;genome-wide analysis;genomic locus;Genomics;Glycogen;Goals;Hepatocyte;Heritability;High Prevalence;Hispanic ancestry;Hispanic Populations;Histologic;Histology;Human;Image;improved;Individual;insight;Investments;Knock-out;Link;Liver;Liver diseases;loss of function;Maps;Measures;Medical;Meta-Analysis;minimal risk;Minority Groups;multi-ethnic;National Heart, Lung, and Blood Institute;non-alcoholic fatty liver disease;novel;Obesity associated liver disease;obesity genetics;Pathology;Population;population based;Population Heterogeneity;Predisposition;Prevalence;prevent;Prevention;Public Health;Publishing;rare variant;Resources;Risk;Role;Signal Transduction;targeted treatment;Testing;Therapeutic Intervention;Time;Trans-Omics for Precision Medicine;United States National Institutes of Health;Variant;Weight;whole genome;Work;X-Ray Computed Tomography

PROJECT_TITLE: Identification and Characterization of Loci Associated with Non-alcoholic Fatty Liver Disease

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


NIH_SPENDING_CATS: Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE COUNTY

ORG_STATE: MD

PHR: Narrative The goal of U-RISE at UMBC is to develop a diverse pool of undergraduates, prioritizing underrepresented races and ethnicities, students with disabilities, and students from disadvantaged backgrounds, who complete their baccalaureate degree, and transition into and complete biomedical, research-focused, higher-degree programs (e.g., Ph.D. or M.D./Ph.D.), and pursue biomedical research careers. Increasing diverse perspectives within the biomedical research workforce will maximize potential for complex scientific problem-solving. The program will provide a combination of activities to ensure: (i) excellence in academic science, (ii) adapting to the intensity of contemporary scientific research, (iii) student interest in pursuing a Ph.D. degree and subsequent career in biomedical research, (iv) selection of graduate school and successful completed applications, and (v) a value placed on student mental health and wellness amongst the rigor.

PI_NAMEs: ROBINSON, PHYLLIS R (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Admission activity;Advisory Committees;Bachelor's Degree;Baltimore;Biomedical Research;career;college;community college;County;course development;Degree program;design;disabled students;Doctor of Medicine;Doctor of Philosophy;Eligibility Determination;Enrollment;ethnic minority;faculty mentor;Financial Support;Funding;graduate school;Hour;Institution;interest;Internships;low socioeconomic status;Maryland;Mental Health;Monitor;Participant;Performance;Policies;programs;racial minority;recruit;Research;Research Ethics;Research Personnel;Research Support;Research Training;Science;Science, Technology, Engineering and Mathematics;Students;summer research;Surveys;Training;undergraduate research;undergraduate student;Underrepresented Students;Universities;Well in self;Writing

PROJECT_TITLE: U-RISE at University of Maryland Baltimore County

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Genetics;Kidney Disease

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: There is no change to the Public Health Relevance Section as previously submitted.

PI_NAMEs: PIRET, SIAN  (contact)

PROGRAM_OFFICER_NAME: SADUSKY, ANNA BURKART

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Address;Affect;anaerobic glycolysis;Automobile Driving;Autophagocytosis;Biology;Branched-Chain Amino Acids;Catabolism;Cells;Chronic Kidney Failure;Citric Acid Cycle;Clinical;Compensation;Complex;design;Development;Drug Design;Enzymes;Family;fatty acid oxidation;Fatty Acids;Fibrosis;FRAP1 gene;gene repression;Genes;Genetic Transcription;Glycolysis;Goals;Grant;Human;improved;In Vitro;injured;Injury;injury and repair;Isoleucine;Kidney;knock-down;Leucine;Link;member;Metabolic;Metabolic Pathway;Metabolism;Mitochondria;Morbidity - disease rate;mortality;mouse model;Mus;nephrotoxicity;new therapeutic target;novel;novel therapeutics;Outcome;overexpression;oxidation;Oxidative Phosphorylation;Oxygen Consumption;Pathogenesis;Pathway interactions;Patients;Pilot Projects;Process;Production;protective effect;public health relevance;Recovery;Regulation;Reporting;Research;Respiration;restoration;Risk Factors;Role;Severities;Signal Transduction;small molecule;Testing;Therapeutic;transcription factor;Transcriptional Regulation;Up-Regulation;Valine;Zinc Fingers

PROJECT_TITLE: Role of branched-chain amino acid catabolism in the proximal tubule

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE This project concerns spatial integration of light by a ganglion cell photoreceptor that connects the eye to the brain and senses light to drive the often-subconscious effects of light on physiology and behavior. The proposed experiments will define how phototransduction is integrated across the photoreceptor cell’s subcellular compartments and how spatial integration emerges at the population level, providing insights that are likely to generalize to other types of sensory neurons. The knowledge gained in this project will be important for developing therapeutics that compensate for disruptions in light’s regulation of critical functions like circadian rhythms, mood, and sleep.

PI_NAMEs: CAVAL-HOLME, FRANKLIN  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Address;Afferent Neurons;Area;Axon;Behavior;biophysical analysis;Biophysical Process;Brain;Cells;circadian pacemaker;circadian regulation;Circadian Rhythms;Closure by clamp;Compensation;Complement;Cone;constriction;Data;Dendrites;desensitization;Distal;Electrophysiology (science);Exhibits;experimental study;Eye;Fire - disasters;ganglion cell;Goals;Human;Image;insight;Investigation;Knowledge;Label;Lasers;Length;Light;light effects;light intensity;Lighting;Macaca;Mammals;Measures;Mediating;melanopsin;Methods;Miosis disorder;Moods;Mus;neuronal cell body;Neurons;Optic Disk;optical disc;Output;patch clamp;Patch-Clamp Techniques;Pattern;Perception;Perforation;Peripheral;Photons;Photophobia;Photoreceptors;Photosensitivity;Phototransduction;Physiology;Population;Preparation;preservation;Preservation Technique;Presynaptic Terminals;Property;Proteins;Protocols documentation;Psychophysics;Publishing;Pupil;receptor;Reflex action;Regulation;response;Retina;Retinal Ganglion Cells;Rod;Shapes;Signal Transduction;Site;Sleep;Slice;spatial integration;Stimulus;Subconscious;Supporting Cell;Surface;Testing;Therapeutic;transmission process;two-photon;Variant;Vision;Visual;Visual Pathways;voltage clamp

PROJECT_TITLE: Subcellular Origins of Extensive Spatial Integration by Ganglion Cell Photoreceptors


NIH_SPENDING_CATS: Aging

ORG_CITY: SYRACUSE

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

PHR: Narrative of Public Health Relevance V-ATPases are present in all cells and help control pH in specific sub-compartments, degrade defective proteins, and respond to environmental stresses. Their dysfunction is associated with diseases like Alzheimer’s disease, cancer, and osteoporosis. V-ATPases are involved in many functions, and it is hard to target subpopulations of V-ATPases therapeutically. We are characterizing regulators of V-ATPases in specific locations. Targeting these regulators might make it possible to treat diseases associated with aberrant V-ATPase activity.

PI_NAMEs: KANE, PATRICIA M (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Acute;Aging;Albers-Schonberg disease;Alzheimer's Disease;Binding;Cell membrane;Cell Physiology;Cells;Chronic;Complex;deafness;Defect;Disease;Distal;Endocytosis;Endosomes;Environment;environmental stressor;Enzymes;Epilepsy;Eukaryota;Eukaryotic Cell;extracellular;Functional disorder;fungus;In Vitro;Infertility;Link;Lipids;Location;Lysosomes;Malignant Neoplasms;Mammalian Cell;Membrane;Mutation;Neoplasm Metastasis;Nerve Degeneration;Organelles;Osteoporosis;Peripheral;pH Homeostasis;Phosphatidylinositols;Phospholipids;Play;Process;Protein Isoforms;Proteins;Proton Pump;public health relevance;Pump;Regulation;Renal tubular acidosis;Role;Structure;Therapeutic;vacuolar H+-ATPase;Vacuole;virtual;Virus;Yeasts

PROJECT_TITLE: Regulation and Cellular Functions of V-ATPases

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


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

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

ORG_CITY: RALEIGH

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: PROJECT NARRATIVE/PUBLIC HEALTH RELEVANCE STATEMENT  The abysmal survival rate of patients with advanced colon cancer is attributable to resistance to chemotherapies that have been designed to efficiently stop proliferation and initiate apoptosis in cancer cells, but fail to appreciate the pro-chemoresistance signals emanating from cells surrounding the tumor. Proposed studies will explore the impact of enteric glial cells, which form a dense network infiltrating colon adenocarcinomas, and yet have been understudied in colon carcinogenesis, and in particular colon cancer resistance to chemotherapies. Therefore, the outcomes of this project will not only improve our understanding of the cellular and molecular mechanisms driving colon cancer chemoresistance but may also demonstrate the therapeutic potential of developing strategies combining targeted therapies against enteric glial cell-derived chemoprotective ligands and traditional chemotherapy regimens.

PI_NAMEs: VAN LANDEGHEM, LAURIANNE CHANTAL (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: 3-Dimensional;Apoptosis;ataxia telangiectasia mutated protein;ATM Signaling Pathway;Automobile Driving;Biological;cancer cell;cancer stem cell;cancer therapy;carcinogenicity;Cell Line;Cells;Chemoprotection;Chemoprotective Agent;Chemoresistance;chemotherapy;Chemotherapy-Oncologic Procedure;Coculture Techniques;Colon;Colon Adenocarcinoma;colon carcinogenesis;Colon Carcinoma;Colonic Neoplasms;Complex;Cues;Cytoprotection;design;Development;Dinoprostone;DNA Damage;DNA Repair;Drug resistance;Drug usage;Embryo;Engraftment;Enteral;Enteric Nervous System;Fluorouracil;Follistatin;Gene Targeting;Genetic;glial activation;Glial Fibrillary Acidic Protein;Growth;healing;Human;Immunodeficient Mouse;improved;In Vitro;in vivo;Induction of Apoptosis;Infiltration;Knockout Mice;Ligands;Light;Maintenance;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Molecular;Molecular Profiling;mouse model;neoplastic cell;Neuroglia;new therapeutic target;novel;novel therapeutics;Operative Surgical Procedures;Outcome;oxaliplatin;paracrine;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Probability;Production;Prognosis;Proliferating;protective effect;public health relevance;Rattus;Resistance;resistance factors;response;sensor;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;stem cell survival;Survival Rate;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Time;Tissues;Transgenic Mice;Treatment Efficacy;tumor;tumor microenvironment;Tumor Stem Cells;WFDC2 gene

PROJECT_TITLE: Enteric Glia is New Biological Target to Block Drug Resistance in Colon Cancer

STUDY_SECTION: MCTB

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics B Study Section[MCTB]


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences

ORG_CITY: COLLEGE STATION

ORG_DEPT: PSYCHOLOGY

ORG_NAME: TEXAS A&M UNIVERSITY

PHR: PROJECT NARRATIVE  Comorbidity in anxiety disorders is common, exerts tremendous personal and societal costs, is difficult to treat and is associated with increased negative emotionality. Little is known about the neural mechanisms that promote anxiety comorbidity and negative emotionality. The current project focuses on a neural profile that corresponds to increased comorbidity load across the anxiety disorders and could lead to better ways to diagnose and treat the most burdened anxiety patients.

PI_NAMEs: MACNAMARA, ANNMARIE EILEEN (contact)

PROGRAM_OFFICER_NAME: WIJTENBURG, SARAH ANDREA

PROJECT_TERMS: Amygdaloid structure;Anterior;Anxiety;Anxiety Disorders;anxiety-related disorders;Attention;Attenuated;blood oxygenation level dependent response;Brain;burden of illness;Categories;cingulate cortex;Clinical;Clinical assessments;clinically relevant;comorbidity;Data;Data Collection;Detection;Development;Diagnosis;Diagnostic;diagnostic platform;Diffuse;Dimensions;disability;Disease;Disease remission;Dorsal;dysphoria;Electroencephalography;Emotional;Emotions;Epidemiology;Etiology;experience;falls;Fright;Functional disorder;Functional Magnetic Resonance Imaging;functional magnetic resonance imaging/electroencephalography;Future;Generations;Genetic;Image;improved;indexing;Individual;insight;Interview;Link;Measures;Methods;Modeling;negative affect;Negative Valence;neural;neural circuit;Neurobiology;neuromechanism;neurophysiology;novel;Outcome;Participant;Pathway interactions;Patient Self-Report;Patients;prevent;Process;prospective;Psychopathology;Recovery;recruit;Relapse;Research Domain Criteria;Risk;Role;Sampling;societal costs;stimulus processing;Stress;stress reactivity;Stressful Event;stressor;Sum;Symptoms;System;Testing;Transcend;Work

PROJECT_TITLE: HARM-A: A neurobiological predictor of comorbidity and stress reactivity in anxiety disorders

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ORG_CITY: AMHERST

ORG_DEPT: PHYSIOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: Project Narrative: Ventricular tachyarrhythmias are responsible for 300,000 sudden cardiac deaths a year in the US. In addition, the ever-increasing prevalence of obesity also poses a significant burden on the health care system with increased morbidity and mortality associated with fatal ventricular arrhythmias. In this project, we will a multi-modal and multi-scale approach to characterize how obesity induces ventricular arrhythmias in donor human hearts and use that knowledge to potentially develop new markers to predict and treat ventricular arrhythmias in a clinical setting.

PI_NAMEs: ARAS, KEDAR KIRTIKUMAR (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: adipocyte biology;adiponectin;Adipose tissue;Anatomy;Anti-Inflammatory Agents;Arrhythmia;Bioinformatics;Body mass index;Calcium;calmodulin-dependent protein kinase II;Cardiac;Catecholamines;Categories;Clinical;Coupling;cytokine;Data;Development;Down-Regulation;Experimental Designs;experimental study;Fatty acid glycerol esters;Future;Genetic Transcription;Healthcare Systems;Heart;Heart failure;Human;Hyperactivity;IL6 gene;Incidence;Inflammation;Inflammatory;insight;Interleukin-6;Isoproterenol;Knowledge;Link;Maps;Mediating;Mediator;Mentors;Molecular;Morbidity - disease rate;mortality;multimodality;next generation sequencing;novel marker;Obesity;obesity treatment;Optics;Organ;Overweight;paracrine;Paracrine Communication;Phase;Physiological;Play;Predisposition;Prevalence;Risk;Risk Factors;Role;Site;Stimulus;sudden cardiac death;Tachyarrhythmias;Testing;Tissues;Toll-like receptors;Training;transcriptome;transcriptome sequencing;Up-Regulation;Ventricular;Ventricular Arrhythmia;Ventricular Fibrillation;Ventricular Premature Complexes;Ventricular Tachycardia;Western Blotting

PROJECT_TITLE: Role of epicardial adiposity as a local mediator of VT/VF dynamics in donor human hearts

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


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

ORG_CITY: Boston

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: TUFTS UNIVERSITY MEDFORD

PHR: PROJECT NARRATIVE  A major bottleneck in untargeted metabolomics workflows is assigning chemical identities to measured spectra. This work proposes several novel computational techniques to annotate spectral measurements. We anticipate that this work will advance discoveries in biomedical research and have direct benefits to human health.

PI_NAMEs: HASSOUN, SOHA  (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Address;Algorithms;annotation  system;Biological;biomarker discovery;Biomedical Research;Chemicals;Computational Technique;Data;data modalities;Data Set;data sharing;deep learning;deep learning model;experience;experimental study;Gases;Goals;graph neural network;Health;Human;improved;innovation;instrument;Learning;Liquid substance;Maps;Mass Spectrum Analysis;Measurement;Measures;Metabolism;metabolomics;Modeling;Molecular;neural network;novel;Ontology;Performance;Research;success;tandem mass spectrometry;Technology;Training;Translations;Work

PROJECT_TITLE: Deep Learning Models for Metabolomics Analysis


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: PULLMAN

ORG_NAME: WASHINGTON STATE UNIVERSITY

PHR: Project Narrative Heroin withdrawal is characterized by aversive physical and emotional states which can lead to recurrent drug seeking and relapse. The goal of the proposed studies is to gain insight into the contribution of paraventricular thalamic circuits in opioid withdrawal syndrome and heroin seeking, such that novel therapeutic strategies can be identified for the treatment of opioid addiction.

PI_NAMEs: GIANNOTTI, GIUSEPPE  (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Abstinence;Acute;Attenuated;Automobile Driving;Behavior;Brain;Cells;Clinical Research;cocaine relapse;Cocaine withdrawal;Cognitive Therapy;Data;drug craving;Drug usage;Electrophysiology (science);Emotional;experience;experimental study;Exposure to;Extinction;Genetic;genetic approach;Glutamates;Goals;Heroin;Hyperalgesia;In Vitro;in vivo;insight;Knowledge;Long-Term Depression;Measures;Mediating;Mentors;Modality;Modeling;Morphine;Mus;N-Methylaspartate;Naloxone;neural circuit;Neurons;novel;novel therapeutic intervention;Nucleus Accumbens;Opiate Addiction;Opioid;opioid epidemic;opioid use disorder;opioid withdrawal;Opsin;optogenetics;Pain;pain sensitivity;patch clamp;Pathway interactions;Pharmaceutical Preparations;Phase;Population;postsynaptic;Prefrontal Cortex;Procedures;Protocols documentation;Public Health;Rattus;recruit;Recurrence;Relapse;relapse prevention;relapse risk;Research;Rodent Model;Role;Self Administration;Slice;Structure of paraventricular nucleus of thalamus;Substance Withdrawal Syndrome;Synapses;Testing;Thalamic structure;Therapeutic Intervention;Training;United States;Withdrawal;Withdrawal Symptom

PROJECT_TITLE: Paraventricular thalamic control of opioid withdrawal and relapse


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

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Acute myeloid leukemia (AML) is an aggressive form of leukemia and approximately 20-30% of AML patients harbor an activating mutation in the FLT3 receptor tyrosine kinase, which is associated with decreased survival and an increased rate of disease relapse. This application describes experiments aimed at testing the effects of 150030, a small molecule inhibitor of FLT3 and SRC family kinases, on AMLs using genetically engineered syngeneic and PDX models, with a long term goal of conducting clinical trials in patients.

PI_NAMEs: REDDY, E PREMKUMAR (contact)

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Animal Model;Animals;Aspartate;Attention;Binding;Biological Assay;Biological Availability;Biological Models;Bone Marrow;Cell Line;Cell Survival;Cells;Cessation of life;chemotherapy;Clinical;Clinical Research;Clinical Trials;clinically relevant;Combined Modality Therapy;comparative efficacy;compare effectiveness;Conduct Clinical Trials;Cytarabine;Dasatinib;Daunorubicin;Differentiation and Growth;Disease Progression;Disease remission;drug testing;efficacy evaluation;Exhibits;experimental study;FDA approved;FLT3 gene;Genes;Genetic Engineering;Goals;Hematopoietic stem cells;In complete remission;In Vitro;Induction of Apoptosis;inhibitor;kinase inhibitor;leukemia;leukemia treatment;Malignant - descriptor;MAP Kinase Gene;Measures;Medical;Methods;Modeling;Molecular Conformation;Mus;Mutagenesis;mutant;Mutation;Myeloid Cells;Nature;neoplastic cell;Nude Mice;Oral;overexpression;Pathway interactions;patient derived xenograft model;patient response;Patients;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;PI3K/AKT;PKC412;placebo group;Placebos;Population;Process;Protein Kinase C;Protocols documentation;Receptor Protein-Tyrosine Kinases;Recurrent disease;Relapse;relapse patients;Remission Induction;Resistance;resistance mechanism;response;Risk;Route;Signal Pathway;small molecule;small molecule inhibitor;src-Family Kinases;Stat5 protein;Survival Rate;System;Testing;theories;Therapeutic;tumor;Work;Xenograft procedure

PROJECT_TITLE: Targeting FL3 and SRC kinases for AML therapy


NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Dental, Oral, and Craniofacial Disease;Rare Diseases

ORG_CITY: HANOVER

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: PROJECT NARRATIVE The long-term survival and quality of life of head and neck cancer patients that undergo surgical resection are pivotal on the ability of the surgeon to fully remove the tumor while avoiding healthy normal tissue structures. Our capacity to successfully obtain tumor-free surgical margins is limited by our ability to visualize microscopic residual tumor cells. The proposed paired-agent imaging technique allows the separation of bound signal from non-specific signals due to plasma transport kinetics, and tissue leakage that plagues single fluorescent tracer techniques. If successful, this technology will ultimately allow clinicians to identify and remove involved tumor margins to maximize patient survival and reduce life-long surgery-induced morbidities.

PI_NAMEs: SAMKOE, KIMBERLEY  (contact)

PROGRAM_OFFICER_NAME: TANDON, PUSHPA

PROJECT_TERMS: Antibodies;Binding;Biophysics;Blood Vessels;cancer cell;cancer imaging;Cancerous;canine model;Canis familiaris;clinic ready;Clinical;clinical imaging;clinical translation;Clinical Trials;clinically relevant;clinically significant;Compensation;Complex;Controlled Environment;Cosmetics;density;Dependence;Detection;Development;Dose;Ensure;Epidermal Growth Factor Receptor;Excision;extracellular;Extravasation;Face;Fluorescence;Fluorescent Dyes;Goals;head and neck cancer patient;Head and Neck Squamous Cell Carcinoma;Head and neck structure;Head and Neck Surgery;Human;Image;Image Analysis;imaging agent;imaging capabilities;imaging modality;imaging system;Imaging Techniques;Immunohistochemistry;improved;in vivo;Injections;innovation;Investigational Drugs;Kinetics;Lead;Ligand Binding;Light;Lymphatic clearance;Magnetic Resonance Imaging;Malignant Neoplasms;Microscopic;Modeling;molecular imaging;Morbidity - disease rate;mortality risk;Mus;Neck Cancer;neoplastic cell;Noise;Normal tissue morphology;Operating Rooms;Operative Surgical Procedures;Oral;overexpression;Pathologist;Patient-Focused Outcomes;Patients;Perfusion;Physiological;Plasma;Production;Prognosis;Quality of life;real-time images;receptor;receptor binding;receptor expression;Receptor Signaling;Research Personnel;Residual Neoplasm;Resolution;Signal Transduction;Structure;Surgeon;Surgical margins;Surgical Models;System;targeted agent;Techniques;Technology;Texture;Therapeutic;Time;Tissues;Tracer;tumor;Tumor Tissue;Visualization;volunteer;Xenograft procedure

PROJECT_TITLE: Paired-agent imaging for resection during surgery (PAIRS) for head & neck cancers

STUDY_SECTION: CMIP

STUDY_SECTION_NAME: Clinical Molecular Imaging and Probe Development[CMIP]


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative: Aside from these few examples, the prevalence and functions of alternative polyadenylation (APA) in a wide spectrum of human traits and diseases remain largely unknown. We propose to develop innovative bioinformatics and experimental methods for identifying 3′UTR APA quantitative trait loci (3′aQTLs) and nominating APA-linked disease/trait susceptibility genes in a wide variety of cell types and environmental factors, followed by in vivo functional characterization using our unique CRISPR engineering system. We expect to establish APA as an emerging and important molecular phenotype to explain a large fraction of GWAS risk SNPs, leading to significant novel biological insights into the genetic basis of APA and APA-linked susceptibility genes in a wide spectrum of human traits and diseases. 1

PI_NAMEs: LI, WEI  (contact)

PROGRAM_OFFICER_NAME: LI, JERRY

PROJECT_TERMS: 3' Untranslated Regions;Algorithms;Atlases;Binding Sites;Bioinformatics;Biological;Cancer-Predisposing Gene;cell type;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Computer Models;Data;Disease;Engineering;Environmental Risk Factor;Experimental Models;Gene Expression;Genes;Genetic;Genetic Structures;genome wide association study;Genotype;Genotype-Tissue Expression Project;Glioblastoma;Grant;Hereditary Disease;Heterogeneity;Human;human disease;idiopathic pulmonary fibrosis;In Vitro;in vivo;Individual;innovation;insight;Link;Malignant neoplasm of prostate;Methods;MicroRNAs;Modeling;Molecular;molecular phenotype;Nature;neuropsychiatric disorder;novel;Oncogenes;patient subsets;Play;Polyadenylation;Positioning Attribute;Post-Transcriptional Regulation;Prevalence;prostate cancer progression;Proteins;PTEN gene;Pulmonary Fibrosis;Quantitative Trait Loci;Regulation;Regulatory Element;Reporting;Repression;Risk;RNA;RNA Splicing;RNA-Binding Proteins;Role;Sampling;Single Nucleotide Polymorphism;Statistical Methods;Study models;Subgroup;Susceptibility Gene;System;Tissues;trait;Transcript;transcriptome;transcriptome sequencing;treatment effect;Tumor Suppressor Genes;Untranslated Regions;Untranslated RNA;Work

PROJECT_TITLE: Computational and Experimental Modeling of Alternative Polyadenylation

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: HONOLULU

ORG_NAME: HAWAII BIOTECH, INC.

ORG_STATE: HI

PHR: 8. Project Narrative The proposed research is focused on the development of a cross-protective recombinant subunit candidate vaccine against Eastern, Venezuelan and Western Equine Encephalitis Viruses (EEEV, VEEV and WEEV, respectively) that are highly pathogenic in humans. The proposed vaccine combines recombinant glycoproteins from all three New World Alphaviruses into a single formulation. The use of a single vaccine candidate to protect against multiple related encephalitic Alphaviruses provides a valuable medical countermeasure for pandemic threats and a safeguard against biothreats. Validating the success of this vaccine candidate would have a significant impact on human health.

PI_NAMEs: CLEMENTS, DAVID E (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Acute;Adjuvant;aerosolized;Aerosols;Agonist;Alpha Virus;Alphavirus Infections;Americas;Antibody Response;Antibody titer measurement;Antigens;Area;Attenuated;Awareness;Biotechnology;biothreat;bioweapon;Birds;Blood;Brain;C-terminal;Cells;Centers for Disease Control and Prevention (U.S.);Chikungunya virus;Classification;climate change;Collaborations;college;Combined Vaccines;Culicidae;Data;Dengue Virus;Department of Defense;design;Development;Disease;Disease Outbreaks;DNA;Dose;Drosophila genus;Eastern Equine Encephalitis Virus;Encephalitis;epizootic;Equus caballus;Family;Fever;Formalin;Formulation;future outbreak;Glycoproteins;Goals;Hawaii;Headache;Health;Human;Immune response;Immunize;immunogenic;immunogenicity;Inactivated Vaccines;Inbred BALB C Mice;Individual;Infection;Insecta;interest;Investigational Drugs;Laboratories;Licensing;Licensure;Link;liposomal formulation;long-term sequelae;Lymphopenia;Malaise;manufacture;Measures;medical countermeasure;Medicine;Military Personnel;Modeling;Mus;Myalgia;National Institute of Allergy and Infectious Disease;Nausea;Nervous System Disorder;neutralizing antibody;novel;novel vaccines;pandemic potential;pandemic preparedness;Pathogenicity;Periodicals;Phase;Phase I Clinical Trials;pre-clinical;preclinical study;Production;programs;protective efficacy;Protein Subunits;Proteins;prototype;Public Health;QS21;Recombinant Vaccines;recombinant virus;Recombinants;Research;response;Risk;Rodent;Saponins;Subunit Vaccines;success;Survivors;System;technology platform;Testing;Time;Tissues;TLR4 gene;Togaviridae;transmission process;United States Food and Drug Administration;vaccine candidate;vaccine development;vaccine formulation;Vaccines;Venezuelan;Venezuelan Equine Encephalitis Virus;Viral;Viral Vector;Viremia;Virus;Virus Diseases;Virus-like particle;West Nile virus;Western Equine Encephalitis Virus

PROJECT_TITLE: Development of a Cross-Protective New World Encephalitic Alphavirus Subunit Vaccine

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-U(11)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE We compared alveolar fluid from 88 patients with critical COVID-19 with similar samples from 211 patients with pneumonia from other causes to generate a hypothesis about how SARS-CoV-2 injures the lung. We will test this hypothesis using a novel treatment (CRAC channel inhibition) that has shown promise for the treatment of patients with severe or critical COVID-19.

PI_NAMEs: BUDINGER, GR SCOTT ;MISHARIN, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: 2019-nCoV;ACE2;Acute Respiratory Distress Syndrome;Address;Alveolar;Alveolar Macrophages;Alveolitis;Animal Model;Animals;Anti-Inflammatory Agents;Anti-viral Agents;Antibodies;Antigen-Presenting Cells;Attenuated;Biological;Biological Markers;Bronchoalveolar Lavage Fluid;Calcium;Calcium Channel;Cell Communication;Clinical Data;Clinical Trials;Clinical Trials Design;Coronavirus;COVID-19;COVID-19 patient;COVID-19 pneumonia;Credentialing;Cross Reactions;cross reactivity;cytokine;Data;Data Science;direct application;Disease;Dose;Enrollment;env Gene Products;epithelial repair;Feedback;Flow Cytometry;Future;Generations;genomic data;Goals;Heterogeneity;Human;human disease;human tissue;immune activation;Immunology;In Vitro;Infection;Inflammasome;Inflammation;Inflammatory;inhibitor;Interleukin-1 beta;Interruption;Liquid substance;Lung;lymph nodes;Macrophage;Measures;Mechanical ventilation;Mediating;Minority;mutant;Nature;novel;pandemic disease;participant enrollment;pathogen;Patients;pharmacologic;Pneumonia;post SARS-CoV-2 infection;predictive modeling;Production;Public Health;Publications;Pulmonary Inflammation;Research Personnel;Role;Sampling;SARS-CoV-2 infection;Secondary to;severe COVID-19;Severity of illness;Signal Transduction;single-cell RNA sequencing;small molecule;small molecule inhibitor;Sorting;stem;systemic inflammatory response;T memory cell;T-Cell Activation;T-Lymphocyte;Testing;Tissues;transcriptomic profiling;virology;Virus

PROJECT_TITLE: Targeting abnormal alveolar immune activation and failed epithelial repair in COVID-19

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-A(05)]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Macular Degeneration;Neurodegenerative;Neurosciences

ORG_DEPT: OPHTHALMOLOGY

ORG_STATE: PA

PHR: Project Narrative: This meeting brings together the leading researchers, clinician-scientists, and ophthalmologists from around the world to discuss their research in a relaxed and collegial atmosphere. The young investigators will have an opportunity afforded by no other scientific meeting of its type to meet and interact with these outstanding scientists. There is ample evidence that this conference has had profound effects on the scientific careers of many of the young scientists who attended.

PI_NAMEs: ASH, JOHN D (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Academia;Acceleration;Affect;age related;Area;Argentina;Asia;Basic Science;Biochemical;Books;career;Career Choice;career development;Career Mobility;Clinical;Clinical Research;Clinical Trials;Collaborations;Creativeness;Dedications;design;Development;Disease;Disease Progression;disease-causing mutation;drug development;educational atmosphere;Environment;ethnic diversity;Ethnic Population;Exposure to;Eye;Faculty;Feedback;Fees;Foundations;Funding;Funding Agency;Future;Gender;gene therapy;Genes;Genetic Predisposition to Disease;Geography;graduate student;Human;Individual;Industry;Inherited;inherited retinal degeneration;International;Knowledge;lectures;Location;Macular degeneration;meetings;Mind;Minority;Monitor;Mutation;Names;novel;novel therapeutic intervention;novel therapeutics;Ophthalmologist;Participant;Persons;Photoreceptors;Policies;Positioning Attribute;Postdoctoral Fellow;posters;Preclinical Testing;Privatization;professor;programs;Publications;Publishing;Recording of previous events;Relaxation;Reporting;Research;research and development;Research Personnel;Resources;Retinal Degeneration;Rotation;RPE65 protein;Schedule;Scientist;social;Societies;Specialist;stem cell therapy;Structure of retinal pigment epithelium;Students;symposium;Time;tool;Training;Translating;Translational Research;Travel;Underrepresented Minority;Universities;unpublished works;Update;Vision;Vision research;Woman

PROJECT_TITLE: Retinal Degeneration Conference


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

PHR: PROJECT NARRATIVE Non-alcoholic steatohepatitis (NASH)-related cirrhosis is the second leading cause of liver transplantation in the United States. In this proposal, we will investigate the critical contribution of the heterodimeric integrin receptor α4β7 and its ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), in governing hepatic inflammation and fibrosis via immune cell recruitment to the NASH liver. Our primary objective is to identify viable targets for therapy that will halt the development and progression of NASH.

PI_NAMEs: RAEMAN, REBEN  (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Acetates;Address;Attenuated;Automobile Driving;Biological Availability;Butyrates;CD4 Positive T Lymphocytes;Cells;chemokine;Chronic;Cirrhosis;clinically relevant;confocal imaging;cytokine;Data;Development;Diet;Dietary Supplementation;Disease Progression;Event;Face;Fatty Liver;FDA approved;feeding;Fibrosis;Fructose;Genetic;Glucose;Hepatic;Hepatic Stellate Cell;hepatocyte injury;Histologic;Human;Immune;Immune Targeting;immunoregulation;Impairment;improved;In Vitro;Incidence;indexing;Infiltration;Inflammation;Inflammatory;innovation;insight;Integrins;interest;intestinal epithelium;intrahepatic;Investigation;Ligands;Liver;Liver Fibrosis;liver inflammation;liver transplantation;Mediating;Metabolic;microbial;Modeling;Molecular;Monoclonal Antibodies;monocyte;monomer;mouse model;mucosal addressin cell adhesion molecule-1;Mus;non-alcoholic fatty liver;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;Pathogenesis;Pathway interactions;Patients;Play;Primary carcinoma of the liver cells;Propionates;Publishing;receptor;recruit;Reverse Transcriptase Polymerase Chain Reaction;Risk;Role;targeted treatment;Testing;Therapeutic;therapeutic target;therapeutically effective;Tissues;United States;Volatile Fatty Acids;western diet

PROJECT_TITLE: Mechanisms underlying hepatic immune cell recruitment in nonalcoholic fatty liver disease

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Hepatitis;Hepatitis - C;Infectious Diseases;Kidney Disease;Liver Disease;Organ Transplantation;Transplantation

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative The practice of transplanting kidneys from hepatitis C virus (HCV) infected donors into patients without HCV is considered `experimental' by many leaders in the transplant field because of limited information about risks and benefits. Specifically, when patients consider accepting a kidney from a donor with HCV infection, their doctors are not able to provide good information about key issues, including: the risks of not being cured of HCV, whether choosing to accept these kidneys is likely to improve their survival, the long-term function of these kidneys after transplantation, and whether there are additional infectious risks such as developing complications from viruses other than HCV. This multi-center trial seeks to define the safety and determine the most important outcomes after transplanting kidneys from HCV-viremic donors into HCV-negative patients in order to move the practice from experimental to routine clinical care from the perspective of patients, providers, and payers.

PI_NAMEs: GOLDBERG, DAVID SETH;REESE, PETER PHILIP;SCHAUBEL, DOUGLAS EARL (contact)

PROGRAM_OFFICER_NAME: MENDLEY, SUSAN RUTH

PROJECT_TERMS: Acute Hepatitis C;Address;Allografting;American;Anti-viral Agents;Anti-viral Therapy;Benefits and Risks;Biopsy;Blinded;Cholestasis;Chronic Disease;Chronic Kidney Failure;clinical care;Clinical Trials;cohort;Communicable Diseases;comparison group;Confidence Intervals;Consent;Cytomegalovirus;Cytomegalovirus Infections;Data;early experience;Elderly;End stage renal failure;Ethicists;Evaluation;Fibrosis;Glomerular Filtration Rate;Glomerulonephritis;glomerulosclerosis;Goals;graft failure;Health Care Costs;Hepatitis C;Hepatitis C Therapy;Hepatitis C Transmission;Hepatitis C virus;High Prevalence;implantation;improved;Incidence;Inferior;Informed Consent;Injury;Institutional Review Boards;Insurance Carriers;interstitial;Kidney;kidney allograft;kidney biopsy;Kidney Transplantation;Knowledge;Life;Liver diseases;Mediating;Membranoproliferative Glomerulonephritis;Monitor;Multi-Institutional Clinical Trial;Multicenter Trials;off-label use;opioid epidemic;Organ;Outcome;Overdose;Pathologic;Pathologist;Pathology;Patients;Perception;Persons;Pharmaceutical Preparations;Phenotype;post-transplant;Prevalence;Prospective Studies;Protocols documentation;Provider;Quality of life;Renal function;Reporting;Risk;Risk Assessment;risk mitigation;Safety;Series;side effect;Societies;Specimen;standard of care;Standardization;success;System;Testing;transplant centers;Transplant Recipients;Transplantation;Treatment Failure;Uncontrolled Study;Vascular Diseases;Viral;Viremia;Virus;Virus Diseases;Waiting Lists;Work

PROJECT_TITLE: A trial of transplanting Hepatitis C-viremic kidneys into Hepatitis C-Negative kidney recipients (THINKER-NEXT)


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;Hearing Loss;Neurosciences;Rehabilitation

ORG_CITY: ATLANTA

ORG_DEPT: NEUROSURGERY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Hearing loss is widespread in the United States and can affect our ability to follow speech in noisy environments. The proposed research will investigate how head motion can be used to improve hearing, and how this is enabled by central auditory pathways in the brain. This will lay the groundwork for future studies to develop improved neuroprosthetics, such as cochlear implants, to restore natural hearing ability.

PI_NAMEs: RODGERS, CHRISTOPHER  (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: 3-Dimensional;Affect;Animals;Area;Auditory;Auditory area;auditory pathway;Auditory Physiology;Auditory system;Behavior;Behavioral;behavioral response;Biomedical Engineering;Brain;Brain region;career;Child;Cochlear Implants;Communities;Compensation;Complex;coping;Coupling;Crying;Data;design;Disease;Doctor of Philosophy;Ear;ear infection;Electrophysiology (science);empowerment;Environment;equilibration disorder;Equipment;free behavior;Future;Genetic;Goals;graduate student;Head;Head Movements;Hearing;hearing impairment;Hearing problem;Human Resources;Imaging Device;improved;Individual;innovation;Institution;Learning;Left;Link;Location;Machine Learning;Measures;Mediating;Modeling;Monitor;Motion;Motor;motor impairment;mouse model;Mus;National Institute on Deafness and Other Communication Disorders;neural;neural circuit;Neurons;neuroprosthesis;Neurosciences;neurotransmission;New York;optogenetics;Perception;Persons;Physiological;Play;Population;Positioning Attribute;Posture;professor;programs;psychological distress;pup;Recording of previous events;Recovery;rehabilitation strategy;Research;resilience;Resolution;Resources;response;Role;Scanning;Sensory;Sensory Disorders;Side;Signal Transduction;Somatosensory Cortex;sound;Sound Localization;Source;Specialist;Speech;Stimulus;Techniques;tenure track;Testing;Training;United States;Universities;Variant;Vestibular Diseases;vestibular system;Visual Cortex;Work

PROJECT_TITLE: Central auditory pathways for integrating auditory input with head position during active sound localization in mice

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_CITY: DOYLESTOWN

ORG_NAME: JBS SCIENCE, INC.

PHR: Hepatitis B virus (HBV) infection is a global public health concern and causes acute and chronic hepatitis leading to severe liver diseases. Although HBV DNA replication can be suppressed by effective nucleoside analogs, an indefinite course of antiviral treatment is necessary to suppress viral replication continuously due to its ineffectiveness in eliminating integrated HBV DNA and cccDNA. Currently, the treatment goal is to achieve functional cure that is defined as the clearance of the HBV surface antigen (HBsAg), NO clinical test, however, is currently capable of sensitively detect cccDNA from patients. The goal of this application is to develop a cccDNA assay that can be used to detect cccDNA to monitor antiviral treatment efficacy and identify “cured” subjects who can then be free of a life-long regimen of unneeded anti-viral therapy.

PI_NAMEs: LIN, SELENA  (contact)

PROGRAM_OFFICER_NAME: DYALL, JULIE

PROJECT_TERMS: Acute Hepatitis;Affect;anti-hepatitis B;Anti-viral Therapy;Archives;assay development;Biological Assay;Biological Markers;Biopsy Specimen;Biotechnology;bisulfite;Blood;Cell Culture Techniques;Cell Nucleus;Chronic Hepatitis;Chronic Hepatitis B;Chronic Hepatitis C;chronic liver disease;Circular DNA;Cirrhosis;Clinical;cost;Data;design;Detection;detection assay;detection sensitivity;Development;Diagnostic;diagnostic technologies;Disease;DNA;DNA biosynthesis;DNA Sequence;drug development;Drug Discovery Groups;ds-DNA;Episome;Generations;Goals;Hepatitis B;Hepatitis B e Antigens;Hepatitis B Virus;Hepatocyte;HepG2;innovation;intrahepatic;Laboratories;Liver;liver biopsy;Liver diseases;Malignant neoplasm of liver;manufacture;Marketing;Measurement;Measures;Methods;Modification;Monitor;Multi-site clinical study;novel;novel strategies;novel therapeutics;nucleoside analog;Patients;Performance;peripheral blood;Persons;pgRNA;Phase;phase 1 study;Physicians;Plasma;plasmid DNA;Plasmids;Ploidies;Primary carcinoma of the liver cells;Privatization;prospective;Public Health;Regimen;Relaxation;repository;Research;research clinical testing;Risk;Risk Factors;Sample Size;Sampling;Science;serological marker;Serum;Small Business Innovation Research Grant;Surface Antigens;Survival Rate;Technology;Testing;Time;transmission process;Treatment Efficacy;United States National Institutes of Health;Validation;Viral;viral DNA;Virion;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Development of a PCR assay for quantitative detection of HBV cccDNA

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-V(13)]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

PHR: PROJECT NARRATIVE Variants in the noncoding genome have profound effects on human health, but their role in gene regulation is not always clear. This study will investigate the role of quantitative epistasis between cis and trans regulatory variants in regulating complex traits. Insights from this work will advance basic and applied fields of genetics, providing insights into the tunability of gene expression to promote the development of therapeutics for gene regulatory diseases.

PI_NAMEs: ZEBELL, SOPHIA  (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: Address;Affect;Affinity;Alleles;Architecture;Area;Award;base editing;Binding;Binding Proteins;Biological Assay;Biophysics;Breeding;career;career development;Cell Culture Techniques;cell transformation;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Computational Biology;Dependence;Development;Development Plans;Directed Molecular Evolution;Disease;DNA;DNA Binding;DNA Binding Domain;DNA-Protein Interaction;dosage;Educational workshop;Engineering;Enhancers;Environment;experience;Experimental Genetics;experimental study;Family;flexibility;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Epistasis;Genetic Models;Genetic Polymorphism;Genetic Research;genetic resource;Genetic Techniques;genetic variant;Genetic Variation;Genome;genome editing;genome wide association study;genome-wide;genomic variation;Genomics;Genotype;Health;Human;human disease;In Vitro;in vivo;Individual;inflorescence;insertion/deletion mutation;insight;Laboratories;Learning;Linear Models;Link;Maps;Measurement;Mediating;member;Mentors;Modeling;Molecular;Molecular Biology;Molecular Genetics;Morphology;mutant;Outcome;Output;pan-genome;Pathway interactions;Phase;Phenotype;Physical assessment;Plants;Postdoctoral Fellow;prime editing;Productivity;Professional Competence;programs;Publications;Qi;Quantitative Genetics;Quantitative Trait Loci;Regulation;Research;Research Personnel;Research Training;Role;Site;Specificity;System;Technical Expertise;Testing;therapeutic development;tissue culture;Titrations;Tomatoes;Training;trait;transcription factor;transcription factor USF;transcriptome sequencing;Untranslated RNA;Variant;Whole Organism;Work

PROJECT_TITLE: Investigating Cis and Trans Regulation of Complex Phenotypes


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: MIAMI

ORG_NAME: FLORIDA INTERNATIONAL UNIVERSITY

ORG_STATE: FL

PHR: Public Health Relevance/Narrative N6-methyladenosine (m6A) regulates gene expression and is involved in cancer progression. This project seeks to understand the mechanisms for m6A to regulate DNA repair by interplaying with environmentally-induced RNA and DNA base damage in cancer cells. The results from this project will provide new mechanistic insights into environmental carcinogenesis via the interaction between RNA modifications and DNA repair, the key to developing m6A as a new target for cancer prevention, diagnosis, and therapy.

PI_NAMEs: LIU, YUAN  (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: 8-hydroxyguanosine;Address;Affinity;base;Base Excision Repairs;Binding;Biological Assay;BRCA1 gene;cancer biomarkers;cancer cell;cancer diagnosis;cancer drug resistance;cancer prevention;cancer therapy;carcinogenesis;Cell Physiology;Cells;Complex;demethylation;Deposition;Development;Diagnosis;Disease;DNA;DNA Damage;DNA glycosylase;DNA Modification Process;DNA Polymerase β;DNA Repair;DNA-Directed DNA Polymerase;Drug resistance;Environment;environmental carcinogenesis;Environmental Carcinogens;epitranscriptomics;Excision;fat mass and obesity-associated protein;Gel;Gene Expression;Genes;Guide RNA;Hela Cells;Homologous Gene;Human;Hybrids;Immunoprecipitation;insight;invention;knock-down;Knock-out;Knowledge;Laboratories;Lesion;Location;Malignant Neoplasms;Maps;Measures;Mediating;Messenger RNA;Methods;Methylation;Methyltransferase;Modification;new therapeutic target;novel;Outcome;Play;potassium bromate;Prevention;Process;public health relevance;recruit;Regulation;repair enzyme;Resolution;response;RNA;Role;Site;Terminator Codon;Testing;Therapeutic;Toxic Environmental Substances;Transcript;tumor progression

PROJECT_TITLE: N6-methyladenosine (m6A) Interplays with RNA and DNA Damage to Regulate DNA Repair

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Microbiome

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE. Inflammatory bowel disease (IBD) is in part driven by dysregulated interactions between immunoregulatory and inflammatory T cells within the intestine, however, the exact cellular players involved and how these responses become dysregulated are less clear. We show here that conventional STAT3 and BATF-expressing T cells are critical for maintaining intestinal homeostasis through interactions with microbiota-dependent inflammatory γδ T cells. In this proposal we will define STAT3 and BATF-regulated cellular pathways required for these interactions and the role of microbe-dependent γδ T cells in disease using a novel murine IBD model.

PI_NAMEs: OLSON, MATTHEW R (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Address;alpha-beta T-Cell Receptor;Animal Model;Antibiotic Therapy;Automobile Driving;Cell Communication;Cell Physiology;Cells;Cleavage Under Targets and Release Using Nuclease;Colon;Data;Development;Disease;disease model;dysbiosis;Exhibits;Fluorescent in Situ Hybridization;FOXP3 gene;gene network;Gene Targeting;Genes;Genetic Diseases;Genetic Transcription;Goals;gut inflammation;Homeostasis;Human;Human Characteristics;IL17 gene;Immune;Immune response;Immunogenomics;Immunologics;Immunology;immunoregulation;improved;Inflammatory;Inflammatory Bowel Diseases;innovation;insight;Interferon Type II;Intestinal Diseases;intestinal epithelium;intestinal homeostasis;Intestines;Knowledge;Maps;Mediator;Microbe;microbial;microbiota;microorganism interaction;Monoclonal Antibodies;mouse model;Mucous Membrane;Mus;novel;novel therapeutics;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Persons;Play;Population;prevent;programs;Regulation;Regulatory T-Lymphocyte;response;Role;single-cell RNA sequencing;Spontaneous colitis;STAT3 gene;stem;T cell differentiation;T cell response;T-Cell Receptor;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Tissues;transcription factor;Work;γδ T cells

PROJECT_TITLE: A T cell STAT3-BATF axis regulates intestinal gamma delta T cell homeostasis and disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IIDB-K(57)]