NIH_SPENDING_CATS: Aging;Atherosclerosis;Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Nutrition;Obesity;Prevention;Social Determinants of Health

ORG_CITY: BOSTON

ORG_DEPT: NUTRITION

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

PHR: Narrative  Adhering to a Mediterranean dietary pattern can reduce the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD); yet there is scant evidence of this benefit in non-Mediterranean populations for which this diet may not be familiar or accessible, as well of trials examining the mechanisms that contribute to these cardiometabolic improvements. PROMED is a randomized clinical trial among adults in Puerto Rico that will test the efficacy of a culturally-tailored intervention using traditional foods vs. a standard healthy eating program in improving cardiometabolic risk factors in 2yr, and assess if these effects are mediated by metabolite changes, psychosocial factors, or food security and access. PROMED is expected to generate evidence on posited mechanisms of action of a healthy diet and to shift the paradigm from recommending generalized diets to adapting guidance according to the biological, psychosocial, and social needs of diverse populations.

PI_NAMEs: MATTEI, JOSIEMER  (contact)

PROGRAM_OFFICER_NAME: HERREN, OLGA MARINA

PROJECT_TERMS: Address;Adoption;Adult;aged;American;arm;Atherosclerosis;bean;Biological;blood lipid;Blood Pressure;cardiometabolic risk;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;Clinical;Clinical Trials;clinically significant;cohort;Consumption;Control Groups;Cooking Utensils;Counseling;Cultural Backgrounds;culturally appropriate intervention;Data;Diet;dietary;dietary guidelines;Dietary Practices;Dryness;Dyslipidemias;efficacy testing;Equation;Expenditure;experience;Fabaceae;Food;Food Access;food insecurity;food security;fruits and vegetables;glucose metabolism;Goals;good diet;group intervention;Health;health disparity;Health Food;Healthy Eating;High Density Lipoproteins;high risk;high risk population;Household;Household Products;Hypertension;improved;Individual;Intervention;intervention effect;Laboratories;Maintenance;Measures;Mediating;Mediation;member;metabolome;Monitor;multidisciplinary;Non-Insulin-Dependent Diabetes Mellitus;Nutritional;Nutritional Study;Obesity;Olives - dietary;Overweight;Participant;Persons;Plasma;Population;Population Heterogeneity;portion control;precision nutrition;Prediabetes syndrome;predictive signature;prevent;preventive intervention;primary outcome;programs;psychosocial;Psychosocial Factor;Puerto Rico;randomized trial;randomized, clinical trials;Recommendation;Reporting;Resources;response;Risk;Risk Estimate;Risk Factors;Risk Reduction;Role;satisfaction;Secure;Self Efficacy;Self-control as a personality trait;social;Social support;Soybeans;Strategic Planning;Sum;Supermarket;Testing;Text Messaging;texting support;treatment arm;Treatment Efficacy;Triglycerides;United States;United States National Institutes of Health;Vegetable Oils;voucher

PROJECT_TITLE: A culturally-tailored dietary trial for cardiometabolic health in Puerto Rico

STUDY_SECTION: BMHO

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


ADMINISTERING_IC: MH

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Depression;Dissemination and Implementation Research;Health Services;Mental Health;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: SAINT LOUIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PSYCHIATRY

ORG_FIPS: US

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Children living in adversity and poverty are at much higher risk for poor socio-emotional outcomes and later psychopathology; yet, interventions that can improve developmental trajectories by enhancing nurturing caregiving early in development are often unavailable in communities in need. Educational settings offer a promising solution to increase access to innovative parent-child preventive interventions. It is expected that this test of THRIVE will have public health impact by informing best practices related to enhancing the emotional development of at-risk young children to prevent later emotional and behavioral disturbances

PI_NAMEs: KOHL, PATRICIA LYNN;LUBY, JOAN L. (contact)

PROGRAM_OFFICER_NAME: ROONEY, MARY

PROJECT_TERMS: 6 year old;Adherence;Aftercare;aged;Behavioral;Caregivers;caregiving;Characteristics;Child;Child Behavior;Child Rearing;Clinical;Code;Cognitive;Communities;comparison intervention;Complex;Consolidated Framework for Implementation Research;cost;Cost Analysis;cost effective;cost effectiveness;Cost Measures;County;COVID-19 pandemic;depressive symptoms;Development;Early Intervention;Education;effectiveness study;effectiveness testing;effectiveness/implementation design;effectiveness/implementation study;Emotional;emotional functioning;Emotions;experience;Family;functional near infrared spectroscopy;Health Services Accessibility;high risk;Home;Hybrids;implementation barriers;implementation context;implementation cost;implementation outcomes;implementation strategy;improved;improved outcome;inclusion criteria;innovation;Intervention;intervention delivery;Length;Life;Measures;Mediating;meetings;Mental Depression;Mental Health;Methods;neural;optimism;Outcome;Outcome Measure;Outcome Study;Parent-Child Relations;Parenting Education;Parents;Population;post intervention;Poverty;prevent;Prevention;preventive intervention;primary caregiver;Professional counselor;programs;Psychopathology;Public Health;Randomized;Resources;response;Risk;school district;Schools;service delivery;Social Functioning;Stress;symposium;System;Testing;Training

PROJECT_TITLE: Promoting Emotional Development Among Young Children Facing Adversity: An Effectiveness Implementation Study in St. Louis Schools

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

ORG_STATE: CA

PHR: PROJECT NARRATIVE The improvement of long-term outcomes for patients with treatment-refractory acute myeloid leukemia (AML) represents one of the highest unmet need for cancer therapy in general. Based on the initial preclinical and clinical studies, we propose to combine new image-guided AML radiotherapy, which spares normal organs, with a novel oligonucleotide-based immunotherapeutic agent, CpG-STAT3 inhibitor, to stimulate patients’ own immune responses against leukemia. The overarching goal is to develop a paradigm-shifting, effective and safer combinatorial treatment for relapsed and recurrent AML patients.

PI_NAMEs: HUI, SUSANTA K;KORTYLEWSKI, MARCIN  (contact)

PROGRAM_OFFICER_NAME: PEREZ, J MANUEL

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adverse effects;Aftercare;Allogenic;Biopsy;Blood Vessels;Bone Marrow;Bone marrow biopsy;cancer cell;cancer therapy;Cause of Death;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Death;Cell Death Induction;Cell Differentiation process;cell mediated immune response;Cell Survival;Cell Transplantation;Cells;Clinical;clinical biomarkers;Clinical Research;Clinical Trials;clinically relevant;combinatorial;Combined Modality Therapy;comparative efficacy;conditioning;cytokine;cytotoxic;cytotoxicity;design;Development;DNA;DNMT3a;Effector Cell;efficacy evaluation;efficacy study;Epigenetic Process;epigenomics;experience;FDA approved;Feedback;Flow Cytometry;Gene Expression;Gene Silencing;Generations;Genetic Transcription;Goals;Growth;Hematopoietic Stem Cell Transplantation;Human;image guided;image-guided radiation;Immune;immune checkpoint;Immune Evasion;Immune response;Immunocompetent;Immunodeficient Mouse;immunogenic;immunogenic cell death;immunogenicity;Immunophenotyping;Immunosuppression;Immunotherapeutic agent;Immunotherapy;immunotoxicity;improved;in vivo;in vivo Model;Inflammasome;inhibitor;innovation;Interleukin-6;Intravenous;leukemia;leukemia relapse;leukemia treatment;Leukemic Cell;leukemic stem cell;lymphoid irradiation;Macrophage;Malignant Neoplasms;Marrow;Mediating;Mediator;Modeling;Molecular;Mus;Myeloid Cells;neovascularization;NF-kappa B;Normal tissue morphology;novel;nuclease;oligonucleotide delivery;oligonucleotide therapeutics;Oligonucleotides;Oncogenes;Organ;Patient-Focused Outcomes;Patients;personalized approach;Positioning Attribute;potential biomarker;Pre-Clinical Model;preclinical study;Property;Radiation;Radiation Dose Unit;Radiation Protection;radiation resistance;Radiation therapy;Radiation-Induced Cancer;Radioimmunotherapy;recruit;Recurrence;Recurrent disease;Refractory;Refractory Disease;Regimen;Regulator Genes;Regulatory T-Lymphocyte;Relapse;Reporting;Research;Resistance;Role;Secondary acute myeloid leukemia;sensor;Signal Transduction;Small Interfering RNA;small molecule;Solid Neoplasm;Stat3 protein;Structure;Survival Rate;synergism;System;T cell infiltration;T-Lymphocyte;Testing;Time;timeline;Tissues;TLR9 gene;Toxic effect;trafficking;transcriptomics;translational goal;treatment comparison;Treatment Efficacy;tumor;Tumor Debulking;tumor microenvironment;Tumor-associated macrophages;uptake;Vascularization

PROJECT_TITLE: Myeloid cell-selective, oligonucleotide-based STAT3 inhibition combined with total marrow and lymphoid irradiation for immunotherapy of acute myeloid leukemia

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Neurodegenerative;Neurosciences;Parkinson's Disease;Rehabilitation

ORG_CITY: DALLAS

ORG_DEPT: NEUROSURGERY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Despite the prevalence and disability attributable to Parkinson’s disease (PD), we still do not have an integrated understanding of how brain circuits go awry and cause symptoms in PD. The goal of this proposal is to develop a more comprehensive understanding of motor network dysfunction by recording signals from multiple areas of the brains of patients with PD undergoing deep brain stimulation (DBS) implantation surgery. The knowledge gained will provide a critical framework for the development of novel therapies, contribute to improvements in surgical targeting and techniques, and potentially be used for the design of closed-loop DBS systems, all of which can lead to improving the quality of life of PD patients, improving the efficacy of therapies, and reducing health care expenditures.

PI_NAMEs: POURATIAN, NADER  (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Accounting;Address;Affect;Apomorphine;Area;Basal Ganglia;Behavior;Behavioral;biomarker identification;Bradykinesia;Brain;Clinical;Communication;Coupling;Deep Brain Stimulation;design;Development;disability;Disease;Dissociation;Dorsal;dynamic system;Entropy;Etiology;Event;Failure;Frequencies;Functional disorder;Globus Pallidus;Goals;Health Expenditures;Impairment;implantation;improved;Information Theory;innovation;insight;kinematics;Knowledge;Laws;Measurement;Modeling;Monitor;Motor;Motor Cortex;motor symptom;Movement;Movement Disorder Society Unified Parkinson's Disease Rating Scale;Nature;network dysfunction;novel;novel therapeutics;Operative Surgical Procedures;Parkinson Disease;Pathologic;Pathology;Pathway Analysis;Patients;Pattern;pharmacologic;Phase;Physiological;Physiology;Population;Prevalence;Probability;programs;Publishing;Quality of life;Reporting;Research;Rest;Signal Transduction;Site;Structure of subthalamic nucleus;success;symptomatology;Symptoms;System;Techniques;temporal measurement;Testing;Thalamic structure;Therapeutic;Treatment Efficacy;Variant;volunteer;Work

PROJECT_TITLE: The Pathophysiology of Network Synchrony in Parkinson's Disease

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Edited magnetic resonance spectroscopy (MRS) allows us to measure levels of biologically interesting chemicals in the brain; this project has allowed us to develop edited MRS methods with researchers around the world. In this renewal period, we will study these brain chemicals in a cohort that covers the entire lifespan, address the longstanding technical challenge of unwanted signals, and continue to share methods with collaborators.

PI_NAMEs: EDDEN, RICHARD ANTHONY EDWARD (contact)

PROGRAM_OFFICER_NAME: BARRY, ROBERT LEO II

PROJECT_TERMS: Acceleration;Address;Adolescence;Adopted;Age;aged;Aging;Anatomy;Anterior;Antioxidants;Area;area striata;ascorbate;Aspartate;Back;Brain;Brain region;Chemicals;Child Development;Childhood;Clinical;Code;Cognitive;cohort;Coupled;Data;Data Set;Detection;Development;experimental study;Florida;Functional disorder;Funding;gamma-Aminobutyric Acid;Geometry;Glutamates;Glutamine;Glutathione;Grant;improved;in vivo;in vivo magnetic resonance spectroscopy;indexing;Individual;Infant;Inferior frontal gyrus;interest;Intervention;invention;Life;life span;Location;machine learning method;Magnetic Resonance Spectroscopy;Maryland;Measurement;Measures;Medial;medial temporal lobe;Metabolic;Methodology;Methods;Modeling;Morphologic artifacts;Motor Cortex;N-acetylaspartylglutamate;Nerve Degeneration;neurochemistry;neurodevelopment;Neuromodulator;Neurosciences;Neurotransmitters;novel;Oxidative Stress;Paper;Phase;Physiologic pulse;Prefrontal Cortex;Productivity;Protocols documentation;recruit;Research Personnel;Scanning;Signal Transduction;Site;Temporal Lobe;Time;Universities;Update;Water;Work

PROJECT_TITLE: Universal Edited MRS at 3T

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: The proposed study of paradoxical lucidity is very early stage; refinement of definition, development of a staff-report measure using qualitative and quantitative methods and prevalence estimation are important steps in understanding the phenomenon. Such findings will likely both provide useful tools and inform future basic and intervention research. The study will result in the development of a case-reporting method for use by front-line staff to identify episodes of lucidity, with the potential of involving family and staff caregivers as witnesses who may provide comfort to patients prior to death.

PI_NAMEs: LUCHSINGER, JOSE ALEJANDRO;TERESI, JEANNE A. (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Activities of Daily Living;Address;adjudication;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Assessment tool;Assisted Living Facilities;Basic Science;Beds;Care given by nurses;Caregivers;case finding;Case Study;Categories;Cessation of life;Characteristics;Clinical Trials;Collaborations;Coma;Communication;Complex;Consensus;Data;Dementia;Development;Diagnosis;Diagnostic;Doctor of Philosophy;Educational workshop;end of life;Epidemiology;epidemiology study;Event;Family;Frequencies;Frontline worker;Future;Geriatric Psychiatry;Geriatrics;Gerontology;Goals;Health care facility;Husband;Individual;interest;Intervention Studies;Interview;Knowledge;Link;Literature;Long-Term Care;Measurement;Measures;Medical;Methodology;Methods;Modification;multidisciplinary;National Institute on Aging;Nature;Nervous System Disorder;Neurologic;Neurology;Neurons;Neurosciences;non-verbal;Nursing Homes;Participant;Patients;Persons;Phase;Pilot Projects;Population Study;Positioning Attribute;Prevalence;Probability;Procedures;Property;Psychology;Psychometrics;Qualitative Methods;Rain;Recovery;remediation;Reporting;Research;response;Retrospective Studies;Sampling;Signal Transduction;statistics;symposium;Synapses;tool

PROJECT_TITLE: Measurement and estimation of lucidity prevalence in persons with dementia and neurological disorders


ADMINISTERING_IC: AI

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Cancer;Digestive Diseases;Orphan Drug;Physical Injury - Accidents and Adverse Effects;Prevention;Radiation Oncology;Rare Diseases

ORG_CITY: HUMMELSTOWN

ORG_NAME: APOGEE BIOTECHNOLOGY CORPORATION

ORG_STATE: PA

PHR: PROJECT NARRATIVE  With the goal of emergency preparedness, the NIAID is seeking drugs to prevent acute tissue damage and chronic pathologies resulting from accidental or terroristic exposure to ionizing radiation. The first-in-class, clinical-stage sphingosine kinase-2 inhibitor opaganib has anticancer and anti-inflammatory activity in many animal models, including Gastrointestinal Acute Radiation Syndrome in mice. The present studies will provide critical pharmacologic and mechanistic information needed for approval of opaganib as a medical countermeasure to protect people against radiation poisoning.

PI_NAMEs: SMITH, CHARLES D (contact)

PROGRAM_OFFICER_NAME: VEDAMONY, MERRILINE M

PROJECT_TERMS: Accidents;Acute;Address;Affect;Animal Model;animal rule;Animals;anti-cancer;Anti-Inflammatory Agents;Apoptosis;authority;Autophagocytosis;Biochemical;Biological Availability;Biological Markers;Bone Marrow;c-myc Genes;Cell Cycle Arrest;Cell Death Induction;cell killing;Cell Physiology;Cell Survival;Ceramides;chemical stability;Cholangiocarcinoma;Chronic;Clinical;Clinical Trials;cytokine;Department of Defense;Development;DNA Damage;DNA lesion;DNA Repair;Dose;Down-Regulation;drug development;Drug Kinetics;efficacy study;emergency preparedness;Epithelial Cells;Event;Exposure to;Future;gastrointestinal;Generations;Goals;Human;improved;in vitro activity;in vivo;Induction of Apoptosis;Inflammation;Inflammatory;inhibitor;Interleukin-6;intestinal epithelium;Investigational Drugs;Ionizing radiation;irradiation;liquid chromatography mass spectrometry;Malignant neoplasm of prostate;Mediating;medical countermeasure;Methods;Modeling;Molecular Target;mortality;Multiple Myeloma;Mus;National Institute of Allergy and Infectious Disease;NF-kappa B;novel therapeutics;Oral;Oral Administration;Outcome;Pathology;Patients;Persons;Pharmaceutical Preparations;pharmacodynamic biomarker;pharmacologic;Pharmacotherapy;Phase;Phase I Clinical Trials;Phase II Clinical Trials;Plasma;Pre-Clinical Model;pre-Investigational New Drug meeting;prevent;Process;Production;programs;Proteins;Qualifying;Radiation;Radiation Accidents;radiation countermeasure;Radiation Dose Unit;radiation effect;Radiation exposure;Radiation induced damage;Radiation Induced DNA Damage;Radiation Protection;Radiation Toxicity;radioprotected;repaired;research and development;response;Role;Safety;Sampling;severe COVID-19;Signal Pathway;Small Business Innovation Research Grant;Solid Neoplasm;Sphingolipids;sphingosine 1-phosphate;sphingosine kinase;Testing;Tissues;TNF gene;Toxicology

PROJECT_TITLE: Opaganib as a Medical Countermeasure for Gastrointestinal Acute Radiation Syndrome


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Genetics;Hematology;Lymphatic Research;Lymphoma;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Narrative GSK3E functions as essential negative regulator of E-catenin-signaling, which represents a central oncogenic driver throughout most types of cancer. In striking contrast to other cancer-types, we found that B-cell malignancies are not only exempt from activating E-catenin lesions but highly sensitive to E-catenin nuclear accumulation and critically depend on its negative regulation by GSK3E-mediated degradation. To establish a conceptual framework for GSK3E as novel drug-target in refractory B-lymphoid malignancies, we propose two Aims to (1) elucidate the mechanistic basis of E-catenin-mediated tumor suppression and to (2) develop concepts to leverage GSK3E small molecule inhibitors for therapeutic intervention to overcome drug-resistance in refractory B-cell malignancies.

PI_NAMEs: MÜSCHEN, MARKUS  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: Acute;Adhesions;Alleles;B lymphoid malignancy;B-Cell Acute Lymphoblastic Leukemia;B-Cell Leukemia;B-Cell Neoplasm;B-Lymphocytes;cancer type;Cell Adhesion;Cell Death;Cell Death Induction;Cell membrane;Cell Nucleus;cell transformation;clinical development;Clinical Trials;Complex;Data;Deacetylation;Disease;Drug Combinations;Drug resistance;E-Cadherin;Elements;Engineering;Enhancers;Epithelial Cells;Exclusion Criteria;Exons;experimental study;Future;Gene Expression;gene repression;Genes;Genetic;genome editing;Glucocorticoids;Goals;human stem cells;humanized mouse;In Vitro;in vivo;inhibitor;Knock-in;Label;Lesion;leukemia/lymphoma;loss of function mutation;Lymphoid;lymphoid neoplasm;Malignant - descriptor;Malignant lymphoid neoplasm;Malignant Neoplasms;Mantle Cell Lymphoma;Mediating;member;mouse model;Mutation;nanomolar;Nervous System Disorder;new therapeutic target;novel strategies;Nuclear;Nucleosomes;Oncogenic;patient derived xenograft model;patient subsets;Patients;Phosphorylation;pre-clinical;Refractory;Regulation;Repression;Repressor Proteins;Resistance;response;Role;Safety;Signal Transduction;small molecule;small molecule inhibitor;Solid Neoplasm;stem cells;T-Lymphocyte;Testing;Therapeutic;Therapeutic Intervention;Transcription Coactivator;transcription factor;Transcriptional Activation;Transcriptional Regulation;Treatment Protocols;Tumor Suppression;Zinc Fingers

PROJECT_TITLE: Targeting GSK3B in refractory B-cell malignancies


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Immunotherapy;Infectious Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Toxoplasma gondii is an obligate intracellular pathogen that infects almost all warm-blooded animals and causes severe diseases in fetuses and immunocompromised individuals, such as AIDS patients. I will focus on Toxoplasma secretory effectors and determine the mechanism by which these effectors modulate the innate immune response in rat and human macrophages. This will help to uncover novel anti-Toxoplasma mechanisms from a host-pathogen interaction point of view and has the potential to provide the field with new drug targets against toxoplasmosis.

PI_NAMEs: WANG, YIFAN  (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute;adaptive immune response;Affect;Animals;Binding;Biochemical;Breeding;cell type;Cells;Cessation of life;chronic infection;CRISPR screen;cytokine;Cytoplasmic Granules;Data;Development;Disease;Disease Outcome;Drug Targeting;Fetus;fitness;follow-up;Future;Gene Expression Profile;Genes;Genetic Polymorphism;Genetic Screening;Genetic Transcription;genome-wide;Goals;Growth;Human;Immune system;Immunocompromised Host;Immunotherapy;In Vitro;in vivo;Individual;Infection;Inflammasome;innate immune pathways;Innate Immune Response;insight;Interferon Type II;Knowledge;Laboratory mice;Leadership;Libraries;Ligase;Macrophage;Mediating;Mentors;Modeling;Molecular;Mus;Names;new therapeutic target;novel;novel therapeutics;obligate intracellular parasite;Organelles;Outcome;Parasites;Parasitic infection;pathogen;Pathogenesis;Patients;persistent symptom;Phase;Physiology;Play;Predisposition;Proliferating;Proteins;Proteomics;Rat Strains;Rattus;Rattus norvegicus;receptor;Research Personnel;Resistance;response;rhoptry;Role;secretory protein;single-cell RNA sequencing;skills;Technical Expertise;Testing;Toxoplasma;Toxoplasma gondii;Toxoplasmosis;Training;ubiquitin-protein ligase;Ubiquitination

PROJECT_TITLE: Toxoplasma effector-mediated modulation of innate immune pathways in non-murine macrophages

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


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

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: SUMMARY Despite the promise of the immune checkpoint inhibitors, the outcomes with recently approved immunotherapies remain poor in many cancers. Less than 20% of patients treated with immune checkpoint inhibitors show durable response. This proposal studies a novel mechanism of immune evasion by nanotube-mediated mitochondria harvesting from immune cells by cancer cells, and will develop novel exocyst inhibitors that can overcome this barrier that limits immune checkpoint inhibitors.

PI_NAMEs: SENGUPTA, SHILADITYA  (contact)

PROGRAM_OFFICER_NAME: SOMMERS, CONNIE L

PROJECT_TERMS: 3-Dimensional;4T1;Actins;Autologous;Binding;Biopsy;Breast Cancer Cell;cancer cell;cancer immunotherapy;Cell Communication;Cell Culture Techniques;Cell Death;Cell Survival;cell type;Cells;cellular engineering;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Complex;Cryoelectron Microscopy;Crystallography;Dose;effector T cell;efficacy testing;efficacy validation;Electrons;Exhibits;Genetic;Genus Hippocampus;Guanosine Triphosphate Phosphohydrolases;Harvest;Hour;Human;humanized mouse;Image;Immune;Immune checkpoint inhibitor;Immune Evasion;Immune response;Immunocompetent;Immunologic Memory;Immunologics;Immunotherapy;improved;In Vitro;in vivo;Infiltration;inhibitor;insight;knock-down;Knock-out;Label;Lead;Malignant Neoplasms;Mediating;Metabolic;meter;Minor;Mitochondria;mouse model;Mus;nano;nanoscale;Nanotechnology;Nanotubes;Nature;next generation;Normal tissue morphology;novel;Outcome;overexpression;Patients;Penetration;Pharmacology;Physiology;Play;programmed cell death ligand 1;programmed cell death protein 1;Publishing;rational design;Research;response;Role;Safety;Scanning;Science;Small Interfering RNA;small molecule;small molecule inhibitor;Structure;survival outcome;systemic toxicity;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;therapeutic target;Time;Toxic effect;Toxicokinetics;trafficking;tumor;Tumor Antigens;Tumor Escape;tumor immunology;tumor progression

PROJECT_TITLE: Tunneling Nanotube Inhibitors for Cancer Immunotherapy

STUDY_SECTION: INN

STUDY_SECTION_NAME: Innovations in Nanosystems and Nanotechnology Study Section [INN]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Genetics;Heart Disease;Hematology;Human Genome;Machine Learning and Artificial Intelligence;Precision Medicine;Prevention

ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Clonal hematopoiesis of indeterminate potential (CHIP), which involves the gain of mutations in blood stem cells, is common in older individuals and is linked to increased risk for blood cancers and cardiovascular disease. Genes commonly mutated in CHIP include genes known to regulate epigenetic changes to DNA and splicing of RNA. We will use genome-wide epigenetic and RNA expression data collected from tens of thousands of individuals to investigate whether epigenetic and gene expression patterns differ in individuals with CHIP, and whether this may contribute to their increased risk for cardiovascular disease.

PI_NAMEs: CONNEELY, KAREN  (contact);NATARAJAN, PRADEEP

PROGRAM_OFFICER_NAME: YARDEN, RONIT I

PROJECT_TERMS: Adult;Age;aging related;Alternative Splicing;Atherosclerosis;atherosclerosis risk;Biological Process;Blood;Blood Cells;Blood specimen;Cardiovascular Diseases;cardiovascular disorder risk;cell type;Cells;cohort;Data;Data Discovery;data resource;Data Set;deep learning;deep learning model;deep neural network;Development;Disease;disorder risk;DNA;DNA Methylation;DNMT3a;Epigenetic Process;epigenome;epigenomics;Gene Expression;Gene Expression Profile;Genes;Genetic Transcription;genome sequencing;genome wide association study;genome-wide;Hematologic Neoplasms;Hematopoiesis;Hematopoietic Neoplasms;Hematopoietic stem cells;Immune;Individual;interest;JAK2 gene;Link;Literature;Malignant neoplasm of prostate;Mediating;Mediator;Mendelian randomization;Methylation;methylomics;Modality;Modeling;mortality;Multiomic Data;Mutate;Mutation;mutational status;National Heart, Lung, and Blood Institute;network models;neural network architecture;novel;Older Population;patient stratification;Pattern;Phenotype;Population;PPM1D gene;predictive modeling;Prevalence;Process;programs;Protein Isoforms;response;Risk;risk prediction;risk stratification;RNA Splicing;Role;Signal Transduction;Site;Somatic Mutation;statistics;Testing;Tissues;tool;TP53 gene;Trans-Omics for Precision Medicine;transcriptome;transcriptome sequencing;transcriptomics;Validation;Whole Blood;whole genome;Work

PROJECT_TITLE: Integrated omics analysis of clonal hematopoiesis and cardiovascular disease risk in TOPMed

STUDY_SECTION: GHD

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


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

ORG_DEPT: PHYSIOLOGY

PHR: PROJECT NARRATIVE The proposed project will have direct and immediate relevance for public health. Alzheimer’s disease (AD) is a major cause of dementia in the elderly and an enormous health problem. This Multi-PI project is focused on understanding the molecular mechanisms that lead to early synaptic dysfunction early in the disease. If successful, our studies will facilitate selection of therapeutic agents that have potential to correct memory dysfunction at early stages of AD.

PI_NAMEs: MALTER, JAMES S (contact)

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: Acceleration;Address;Age Months;Alzheimer's Disease;Alzheimer's disease model;Applications Grants;Behavioral;behavioral study;Biochemical;Calcineurin;Calcineurin inhibitor;calcineurin phosphatase;Calcium;Calcium Signaling;Cell Death;Cognitive;cognitive function;Communication;conditioned fear;Data;Defect;Dementia;dentate gyrus;Dependovirus;Detection;Development;Disease;Dominant-Negative Mutation;dosage;Doxycycline;effective therapy;Elderly;Electrophysiology (science);entorhinal cortex;Evaluation;Evolution;excitatory neuron;experience;experimental study;FK506;Functional disorder;Health;Hippocampus;Human;Image;Impaired cognition;In Vitro;in vivo;Incidence;innovation;Label;Laboratories;Lateral;Learning;Light;loss of function;Mediating;Memory impairment;microscopic imaging;Microscopy;Molecular;mouse model;Mus;mutant;network dysfunction;Neurodegenerative Disorders;neuron loss;Neurons;neuropathology;neuroprotection;novel;object recognition;Outcome;overexpression;Pathogenesis;Pathology;Patients;Peptidylprolyl Isomerase;Peripheral;Pharmaceutical Preparations;Play;promoter;prospective;Proteins;Public Health;public health relevance;Publishing;Research Personnel;Resistance;restoration;Role;Schedule;Signal Transduction;Slice;structural imaging;Structure;Synapses;Talents;Techniques;Testing;Therapeutic Agents;Therapeutic Intervention;therapeutically effective;Tissues;Transplant Recipients;transplantation therapy;vector

PROJECT_TITLE: Calcium dysregulation and vulnerability of entorhinal cortex neurons in Alzheimer's disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AN-T(90)S]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Cannabinoid Research;Drug Abuse (NIDA only);HIV/AIDS;Infectious Diseases;Neurosciences;Substance Misuse

ORG_CITY: VALHALLA

ORG_DEPT: PATHOLOGY

ORG_NAME: NEW YORK MEDICAL COLLEGE

PHR: Narrative BMCs play important roles in various physiological contexts, such as transcription, stress response, and in pathophysiological conditions, including cancer, viral infections, and neurodegenerative diseases, and may thus represent a hallmark of HIV/SIV disease. In this proposal, we aim to optimize a novel tool for the isolation and retrieval of in vivo generated BMCs, including blood plasma, CSF, saliva, and intestinal contents from rhesus macaques, then investigate how chronic administration of delta-9-tetrahydrocannabinol (THC) to SIV-infected rhesus macaques affects the composition and function of BMCs. The outcome of these studies will provide illuminating initial example of BMCs as central organizers of biochemistry in vivo, and minimally, the product of this proposal will be an outstanding experimental resource and data sets that will facilitate studies of BMCs in vivo and in the setting of HIV/SIV and THC use.

PI_NAMEs: MOHAN, MAHESH ;OKEOMA, CHIOMA M (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Affect;Alzheimer's Disease;Amyloid fibers;Anti-HIV Agents;Anti-Retroviral Agents;antiretroviral therapy;Attenuated;Behavior;Biochemical;Biochemistry;Bioenergetics;Biological;biological adaptation to stress;Biological Assay;Biological Process;Biology;Blood;Body Fluids;Brain;CCR5 gene;Cell Nucleolus;Cell Nucleus;Cell Physiology;Cells;Cellular biology;Centrosome;Cerebrospinal Fluid;Chemicals;Chronic;Classification;Clinical;Complex;Cytoplasm;Cytoplasmic Granules;cytotoxic;Data;Data Set;Development;Disease;Dyes;electron energy;Electron Microscope;Electron Microscopy;Elements;Environment;Experimental Designs;Exposure to;extracellular vesicles;Genetic Transcription;Goals;HIV;HIV Envelope Protein gp120;HIV Infections;HIV-associated neurocognitive disorder;HIV/AIDS;Homeostasis;Human;in vivo;Individual;Infection;Inflammation;Interruption;Intestinal Content;Knowledge;Link;Liquid Chromatography;Liquid substance;live cell imaging;Macaca;Macaca mulatta;Malignant Neoplasms;marijuana use;Mediating;Membrane;Microscopy;Modeling;Molecular;Molecular Biology;Molecular Target;Morphology;nanocompound;Neurodegenerative Disorders;neuroinflammation;neuronal transport;Neurons;new therapeutic target;Normal Range;novel;Nucleic Acids;Outcome Study;particle;Pathogenesis;Pathologic;Peripheral;Pharmaceutical Preparations;Phase;Physical condensation;physical property;Physiological;Physiological Processes;Plasma;Play;Process;Property;protein aggregation;protein function;Proteins;Proteomics;recruit;Regulation;Reporting;Resources;response;Retrieval;RNA;Roentgen Rays;Role;Saliva;scaffold;Seminal fluid;Shapes;SIV;stress granule;Structure;Symptoms;System;tat Protein;Testing;Tetrahydrocannabinol;Thermodynamics;tool;transcriptomics;transmission process;Viral;Viral Pathogenesis;Viral Proteins;Virus;Virus Diseases;Virus Replication;Visualization;Work

PROJECT_TITLE: Characterizing the physicochemical properties of membraneless condensates and its regulation by delta-9-tetrahydrocannabinol in HIV/SIV infection.


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Genetics;Regenerative Medicine;Rehabilitation

ORG_DEPT: DERMATOLOGY

PHR: Project Narrative Regenerative medicine and cell therapy hold great promise to treat disease. We propose to try to help amputees who use prosthetics but find them painful or the cause of skin problems at the stump site. To do so, we will purify and expand cells from a native palm and sole and inject them into the stump site to hopefully give the stump some of the properties of normal palms and soles such as resilient skin that is pressure adaptive.

PI_NAMEs: GARZA, LUIS ANDRES (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Address;Affect;Amputation;Amputees;Autologous;Biological Models;Biology;Biopsy;Categories;Cell Therapy;Cells;Clinical;Clinical Trials;Collagen;Cytoplasm;Data;decubitus ulcer;Dermis;Development;Disease;Dose;Engraftment;Enrollment;Environment;enzyme replacement therapy;Epithelium;Face;Fibroblasts;foot sole;Freezing;Funding;Future;gene correction;Gene Expression;Gene Expression Profile;gene therapy;Genes;Genetic Diseases;Goals;Grant;healthy volunteer;Histologic;Human;human subject;human tissue;improved;in vivo;Infection;Injections;Intervention;keratinocyte;Large Keratinocyte;Lead;Length;Limb structure;Maryland;Medicine;Mesenchyme;Modeling;Molecular;Morbidity - disease rate;Morphogenesis;Mus;next generation;novel therapeutics;Ontology;organ growth;Pain;Patients;Phase;phase II trial;Population;pressure;prevent;Production;Property;Prosthesis;Prosthesis Design;Protein Deficiency;Proteins;Protocols documentation;Quality of life;regenerative cell;Regenerative Medicine;Research;resilience;Schedule;Side;single-cell RNA sequencing;Site;Skin;stem cell therapy;Testing;Thick;Time;Tissues;transcriptome sequencing;Transduction Gene;treatment optimization;trial enrollment;Viral Vector;Work;wounded soldier

PROJECT_TITLE: Injection of autologous volar fibroblasts to the stump site to allow pressure adaptation and enhanced prosthetic use in amputees


NIH_SPENDING_CATS: Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Recovery of function after nerve damage, which is a very common affliction, involves a regenerative process in which damaged axons within the nerve bundle must regrow back to their target tissues. Regeneration often fails, resulting in chronic pain and functional deficits for many patients, and therapeutic improvements are currently limited by our poor understanding of how this process is controlled. This project will use the zebrafish vagus nerve as a model to identify mechanisms that guide regrowing axons back to their target tissues during regeneration, thereby providing fundamental insights that will inform development of improved therapeutic interventions.

PI_NAMEs: ISABELLA, ADAM JAMES (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Address;Adhesives;Affect;Affinity;American;Axon;axon growth;axon injury;axon regeneration;Back;Biological;Biological Assay;Brain;Cell Adhesion Molecules;cell regeneration;Cell surface;Cells;Chemicals;Chemotactic Factors;Chimera organism;Chronic;chronic pain;Clinical;Complex;Connective Tissue;Coupled;Coupling;Cues;Development;Embryo;Environment;Esthesia;Exhibits;Genetic;Goals;Growth;Growth Cones;Health;Human;Image;improved;In Vitro;in vivo;Injury;insight;knowledge base;Label;Measures;member;Methods;Modeling;Molecular;Morphology;Motor;motor deficit;Muscle fasciculation;Mutagenesis;mutant;Natural regeneration;Nerve;nerve damage;Nerve Fibers;nerve injury;Nerve Regeneration;nerve supply;neural patterning;Neuroglia;Neurons;novel;Outcome;Patients;Pattern;peripheral nerve damage;pharmacologic;Positioning Attribute;Process;programs;Property;Recovery;Recovery of Function;regenerative;reinnervation;Research;Resolution;scaffold;Sensory;Signal Transduction;Structure;Subgroup;Synapses;System;Techniques;Therapeutic;Therapeutic Intervention;therapy development;tissue regeneration;Tissues;tool;transcriptome sequencing;Vagus nerve structure;Zebrafish

PROJECT_TITLE: Mechanisms of Target-Specific Axon Regeneration

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes;Genetics

ORG_CITY: CHARLESTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Project Narrative  The formation of reactive oxygen and nitrogen species (ROS and RNS), such as hydrogen peroxide and nitric oxide, have been implicated in the demise of β-cells during diabetes development. However, we have demonstrated (1) that β-cells maintain a robust antioxidant defense system that allows them to detoxify ROS and RNS, and (2) that interleukin-1β and nitric oxide may play a protective role in β-cells. The broad goals of these studies are to identify mechanisms of β-cell protection from environmental challenges so we can better understand how β-cells fail during the pathogenesis of diabetes.

PI_NAMEs: STANCILL, JENNIFER SUSAN (contact)

PROGRAM_OFFICER_NAME: WANG, XUJING

PROJECT_TERMS: acute infection;Advisory Committees;Affect;animation;Antioxidants;Attenuated;Beta Cell;Biochemical;Blood Glucose;Cell Death;Cell Physiology;Cell Respiration;Cell Survival;cell type;Cells;Cellular Stress;Characteristics;cytokine;Cytoprotection;Data;Development;Diabetes Mellitus;diabetes pathogenesis;Diffuse;Diffusion;DNA;DNA Damage;Drug Metabolic Detoxication;Endocrine;Environmental Protection;Enzymes;experience;experimental study;Free Radicals;Gene Expression;Genes;Genetic;Glucose;Goals;Human;Hydrogen Peroxide;Immunologics;in vivo;Inflammatory;Insulin;insulin secretion;insulinoma;Interferon Type II;Interleukin-1;Interleukin-1 beta;Interleukin-1 Receptors;Investigation;islet;Knock-out;Knockout Mice;Lipids;LoxP-flanked allele;Mentors;Mitochondria;Modeling;Molecular;mouse model;Mus;new therapeutic target;Nitric Oxide;Nitrogen;NOS2A gene;Organism;Oxidants;oxidation;Oxidative Phosphorylation;Oxygen;Pancreas;Pathway interactions;peroxiredoxin;peroxiredoxin I;Peroxonitrite;Phase;Play;preservation;prevent;Production;protective pathway;Proteins;Publishing;Rattus;Reaction;Reporting;Repression;response;Role;Signal Transduction;Signaling Molecule;Structure of beta Cell of islet;Superoxides;System;Testing;therapy design;thioredoxin reductase 1;TXN gene;Viral

PROJECT_TITLE: Protective mechanisms in pancreatic Beta-cells


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Brain Disorders;Chronic Pain;Dental, Oral, and Craniofacial Disease;Headaches;Migraine;Neurosciences;Pain Research;Temporomandibular Muscle/Joint Disorder (TMJD);Women's Health Research

ORG_CITY: COLLEGE STATION

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

PHR: Project Narrative: In this project, we focus on investigation of female-specific role of trigeminal dynorphin in the regulation of temporomandibular disorder (TMD) and migraine overlapping pain. Understanding sex-specific mechanisms of the comorbid TMD and migraine could lead to development of a novel therapy for this trigeminal overlapping pain condition.

PI_NAMEs: TAO, FENG  (contact)

PROGRAM_OFFICER_NAME: GHIM, MELISSA M

PROJECT_TERMS: Address;Animal Model;animal pain;antagonist;Binding;Bradykinin;Bradykinin B2 Receptor;Bradykinin Receptor;comorbidity;Development;Dose;dynorphin receptor;Dynorphins;epidemiologic data;epidemiology study;Female;Genes;Genetic;Goals;Injections;innovation;interdisciplinary approach;Investigation;kappa opioid receptors;knock-down;Knowledge;Ligation;Masseter Muscle;Mediating;Migraine;Molecular;Mus;Neurons;Nitric Oxide;Nitric Oxide Synthase Type I;Nitroglycerin;Nociception;non-opioid analgesic;novel therapeutics;Pain;pain model;Pathway interactions;Patients;Peptides;Play;Prevalence;Production;prodynorphin;Publishing;receptor;Receptor Inhibition;Regulation;Research;Role;sex;Sex Differences;sexual dimorphism;Signal Transduction;small hairpin RNA;Structure of trigeminal nerve spinal tract nucleus;System;Temporomandibular joint disorder pain;Temporomandibular Joint Disorders;Tendon structure;Testing;therapeutic target;Time;transcriptome sequencing;Trigeminal Pain;Trigeminal System;Up-Regulation;Woman;Women's prevalence;Work

PROJECT_TITLE: Female-specific role of trigeminal dynorphin in temporomandibular disorder and its comorbidity

STUDY_SECTION: NPI

STUDY_SECTION_NAME: Neurobiology of Pain and Itch Study Section [NPI]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Congenital Structural Anomalies;Genetics;Neurosciences;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: CAMBRIDGE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: HARVARD UNIVERSITY

PHR: Narrative The project seeks to gain a quantitative understanding of how human stem cell organoids, which have been validated against fetal tissue using single cell and in situ sequencing, respond to and process signals to axially elongate, and how the stem cells in the elongating tailbud are maintained to sustain this elongation. To achieve this goal, the reproducible embryonic stem cell organoid system will be studied using a combination of microscopy, single cell sequencing, statistical inference, mathematical modeling, and molecular biology. In the longer term, a quantitative understanding of how the embryo sustains axial elongation will help better understand the mechanisms of developmental defects.

PI_NAMEs: RAMANATHAN, SHARAD  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Address;Agreement;Anterior;Automobile Driving;Biomedical Engineering;Buffers;Cell Line;cell type;Cells;Complex;CRISPR interference;Data;Defect;Development;Developmental Biology;developmental disease;dynamic system;Embryo;embryo tissue;embryonic stem cell;Ethics;Etiology;experimental study;Feedback;Fetal Tissues;Fibroblast Growth Factor;Gene Expression;Gene Expression Profile;gene regulatory network;Genes;Genetic;Goals;Growth;Human;Human Development;human disease;human model;human stem cells;Image;image processing;In Situ;in situ sequencing;in utero;In Vitro;in vitro Model;in vivo;insight;knock-down;Ligands;Maintenance;mathematical model;Measures;Mesoderm;Mesoderm Cell;Methods;Microscopy;model organism;Modeling;Molecular Biology;Monitor;Morphogenesis;morphogens;Morphology;Mus;neural;Neural tube;Neurons;Noise;novel;optogenetics;Organoids;Paraxial Mesoderm;Pattern;predictive modeling;Predisposition;prevent;Process;progenitor;Proliferating;Proteins;receptor;Reporter;Reproducibility;Research;Role;scoliosis;self-renewal;Signal Pathway;Signal Transduction;single cell sequencing;somitogenesis;Source;spatiotemporal;Spinal Cord;Spinal Dysraphism;stem cell fate;stem cell organoids;stem cells;System;Tail;Testing;Tissues;tool;transcription factor;Transcriptional Regulation;transcriptome sequencing;Tretinoin;Undifferentiated;Vertebrates;WNT Signaling Pathway;Work

PROJECT_TITLE: Measuring and modeling the dynamics ofpatterning in human stem cells

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


NIH_SPENDING_CATS: Brain Disorders;Genetics;Mental Health;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Mutations in calcium channels and proteins involved in decoding calcium signals have been strongly associated with a variety of psychiatric disorders, including autism spectrum disorders and schizophrenia. The research described in this proposal aims to obtain a mechanistic understanding of the processes by which calcium signals influence immature neural progenitor cells to commit to specific identities in the developing brain. The results of our studies will have significant translational potential, providing insights into common pathways underlying psychiatric disease and revealing potentially novel therapeutic targets.

PI_NAMEs: PANAGIOTAKOS, GEORGIA  (contact)

PROGRAM_OFFICER_NAME: KISHORE, SANDEEP

PROJECT_TERMS: Adoption;Agonist;Alternative Splicing;autism spectrum disorder;Brain;Calcineurin;Calcium;Calcium Channel;Calcium Signaling;Cell Cycle;Cell Differentiation process;Cell Lineage;cell type;Cells;Cerebral cortex;Complex;Cues;Data;Defect;detector;Development;developmental disease;Disease;Electroporation;Embryo;Endoplasmic Reticulum;Equilibrium;Event;Exons;extracellular;Failure;Foundations;Functional disorder;Future;Gene Expression;Generations;Genetic;Genetic Models;gliogenesis;Goals;human induced pluripotent stem cells;in utero;in vivo;Individual;insight;Knowledge;L-type calcium channel alpha(1C);Label;Link;Maintenance;Membrane Potentials;Mental disorders;migration;Molecular;Motion;Mus;Mutation;nerve stem cell;neurodevelopment;neurogenesis;Neuroglia;Neuronal Differentiation;Neurons;neuropsychiatric disorder;neuroregulation;Neurosciences;new therapeutic target;NFAT Pathway;nuclear factors of activated T-cells;Output;Pathway interactions;Pattern;pharmacologic;Phosphotransferases;Population Heterogeneity;prevent;Process;programs;Proliferating;Prosencephalon;Protein Isoforms;Proteins;Publishing;Regulation;Reproducibility;Research;response;RNA Splicing;Role;Schizophrenia;sensor;Series;Signal Pathway;Signal Transduction;Signaling Protein;single molecule;stem cell function;Testing;Time;Transcript;transcription factor;transcriptome sequencing;Transducers;translational potential;Variant;voltage

PROJECT_TITLE: Calcium-Dependent Regulation of Neural Fate in Development and Disease

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


NIH_SPENDING_CATS: Aging;Genetics;Neurosciences;Sarcopenia

PHR: Project Narrative Sarcopenia, the age-related decline in skeletal muscle mass and force, is a significant public health challenge due to its key role in the development of physical frailty and loss of independence in the elderly population. While degeneration of the structure of the synapses between motor neurons and muscle fibers and a resultant loss of innervation is widely accepted as a major contributor to sarcopenia, a lack of mechanistic understanding of the causes of these degenerative changes during aging represents a critical barrier to the development of effective and widely applicable interventions to mitigate the devastating effects of muscle loss and improve quality of life for elderly individuals. This research will clarify the role of changes in the expression of the protein Lamin A/C in a specific population of muscle fiber nuclei as important mediator of the recovery of innervation following denervation to identify potential therapeutic targets for preserving muscle during aging.

PI_NAMEs: RUIZ, LLOYD PHILLIP (contact)

PROGRAM_OFFICER_NAME: BOYCE, AMANDA T

PROJECT_TERMS: Acceleration;Action Potentials;Acute;Address;Adult;Age;age group;age related;age related decline;age-related muscle loss;Aging;animal old age;Cell Nucleus;Cells;Chromatin;confocal imaging;Crush Injury;Data;Denervation;Development;disability;DNA Damage;Elderly;Ethnic Origin;Event;Exhibits;frailty;Functional disorder;functional restoration;Gender;Gene Expression;Goals;healthspan;Histologic;Homeostasis;Immunohistochemistry;Impairment;improved;In Situ;Individual;Injury;insight;Intermediate Filament Proteins;Intervention;Investigation;Lamin Type A;Light;Link;Maintenance;Mediating;Mediator;Membrane Proteins;Mobility decline;molecular array;Morphology;Motor Endplate;Motor Neurons;mouse model;Mus;Muscle;muscle aging;Muscle denervation procedure;Muscle Fibers;muscle form;muscle reinnervation;Muscular Atrophy;Nerve;nerve injury;nerve supply;Nervous System;neuromuscular;neuromuscular function;Neuromuscular Junction;Nuclear Envelope;Nuclear Lamina;old mice;Operative Surgical Procedures;Pathologic;Personal Satisfaction;Phenotype;Physiological;Play;Population;Positioning Attribute;postsynaptic;Predisposition;preservation;Process;Property;protein expression;Proteins;Public Health;Quality of life;Recovery;reinnervation;repaired;Reporting;Research;Resolution;Role;sarcopenia;sciatic nerve;Shapes;Skeletal Muscle;skeletal muscle wasting;Socioeconomic Status;Structure;Synapses;targeted treatment;Techniques;Testing;Therapeutic Intervention;therapeutic target;Time;transmission process;Up-Regulation;Wild Type Mouse

PROJECT_TITLE: Lamin A/C is required for maintaining subsynaptic myonuclei integrity

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Established Investigators and Conference Grants Study Section[AGCD-4]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Cardiovascular;Clinical Research;Dementia;Dietary Supplements;Neurodegenerative;Neurosciences;Nutrition;Prevention

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: In this project, we propose using the personalized nutrition framework to test the effect of a brain healthy diet and omics signatures of a brain healthy diet on the brain of participants in the Framingham Heart Study. We will assess the anti-inflammatory and anti-oxidant potential of the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet and its objective omics signatures and assess brain effects using dementia surveillance data and PET-imaging scans. Results from our study will provide important information for future dietary intervention trials for brain aging and dementia.

PI_NAMEs: MELO VAN LENT, DEBORA  (contact)

PROGRAM_OFFICER_NAME: ANDERSON, DALLAS

PROJECT_TERMS: Adherence;Age;aging brain;aging related;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer’s disease biomarker;Amyloid;Amyloid beta-Protein;Amyloid deposition;Anti-Inflammatory Agents;Antioxidants;apolipoprotein E-4;Assessment tool;Biological;Biological Markers;biological systems;biomarker signature;Blood;Body mass index;Brain;Brain Diseases;Cardiovascular Diseases;Chronic;cohort;Cohort Studies;Complex;Cox Proportional Hazards Models;DASH diet;Data;Dementia;dementia risk;design;Diabetes Mellitus;Diet;Dietary Assessment;Dietary Factors;Dietary intake;Dietary Intervention;Dietary Practices;Disease;Disease Outcome;Eating;effective therapy;Energy Intake;Etiology;follow-up;Food;Framingham Heart Study;Frequencies;Functional disorder;Future;Generations;Genetic Determinism;Genome;Goals;good diet;High Density Lipoprotein Cholesterol;imaging biomarker;Impaired cognition;improved;indexing;Individual;Inflammatory;Intake;inter-individual variation;Intervention Trial;Investigation;Lateral;Linear Regressions;Link;Lipids;Liquid substance;Memory;Metabolic;Metabolism;metabolome;metabolomics;Methodology;Nerve Degeneration;Neurodegenerative Disorders;novel;nutrition;Nutrition Assessment;Nutritional;Nutritional status;Nutritional Study;Observational Study;offspring;Outcome;Oxidative Stress;Participant;Pathology;Pathway interactions;Pattern;personalized nutrition;Pharmaceutical Preparations;Physical activity;Plasma;Play;Positron-Emission Tomography;Prevention;Preventive;Process;Questionnaires;Regulation;Reporting;Research;Research Priority;Role;Sampling;Scanning;sex;Sex Differences;Smoking;Strategic Planning;Subgroup;surveillance data;systemic inflammatory response;tau Proteins;Testing;United States National Institutes of Health

PROJECT_TITLE: Metabolic signatures of the MIND diet to objectively investigate with all cause and Alzheimer’s Disease dementia and PET imaging Biomarkers of Alzheimer's Disease

STUDY_SECTION: AIMR

STUDY_SECTION_NAME:
Aging, Injury, Musculoskeletal, and Rheumatologic Disorders Study
Section[AIMR]


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

PHR: PROJECT NARRATIVE Many patients with Alzheimer’s disease (AD) have an increased risk of developing epilepsy, and over 40% of AD patients without a history of epilepsy exhibit subclinical epileptiform activity. Increased expression of the voltage-gated sodium channel SCN8A has been observed in brains from AD patients and mouse models of AD, and we speculate that increased Nav1.6 activity in AD contributes to multiple clinically challenging features of AD, including epileptiform discharges, cognitive impairment, and AD neuropathology. We will use genetic, behavioral, and electrophysiological, approaches to establish the beneficial effects of selectively reducing SCN8A expression in AD.

PI_NAMEs: WONG, JENNIFER C. (contact)

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Anatomy;APP-PS1;Axon;Behavior;behavior change;Behavioral;Biological;Brain region;Characteristics;Clinical;Cognitive;Data;Dementia;Development;Disease;disease phenotype;Disease Progression;Early Onset Alzheimer Disease;Electrophysiology (science);Epilepsy;epileptiform;excitatory neuron;Exhibits;experimental study;General Population;Generations;Genetic;High Prevalence;Hippocampus;Impaired cognition;Incidence;inhibitory neuron;knock-down;Knowledge;Knowledge Portal;Learning;locus ceruleus structure;male;Membrane;Memory;Moods;mouse model;mutant;Mutation;Nervous System Disorder;Neurodegenerative Disorders;Neurofibrillary Tangles;neuroinflammation;neuronal excitability;Neurons;neuropathology;novel;novel therapeutic intervention;novel therapeutics;Pathology;Pathway interactions;Patients;Play;precision medicine;Predisposition;prevent;Prosencephalon;Proteomics;Recording of previous events;Reporting;Resistance;Risk;Role;SCN8A gene;Seizures;Sodium;Sodium Channel;spatial memory;Synapses;tau Proteins;Tauopathies;Therapeutic;therapeutic target;therapy development;translational potential;treatment strategy;voltage

PROJECT_TITLE: Targeting Excitability in Alzheimer's Disease

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: NARRATIVE The goal of the Neurofibromatosis (NF) and Schwannomatosis (SWN) Genes Variant Curation Expert Panel (VCEP) is to develop, apply, and disseminate disease-specific curation guidelines for genes associated with neurofibromatosis type 1 (NF1), Legius syndrome (LS), and schwannomatosis (SWN), including NF2-related schwannomatosis (NF2-SWN, formerly known as neurofibromatosis type 2) and non-NF2-related schwannomatosis (non-NF2-SWN). The team will publish a series of manuscripts describing the ClinGen- endorsed specific guidelines for interpreting germline variants in NF1, NF2, SMARCB1, LZTR1, and SPRED1. This information will standardize the assignment of pathogenicity across academic and commercial labs, will improve the diagnosis clinical management of patients by clarifying the interpretation of both intronic and missense variants, and will increase the number of curated variants deposited in ClinVar. page 1

PI_NAMEs: CASTELLANOS, ELISABETH ;PLOTKIN, SCOTT R (contact)

PROGRAM_OFFICER_NAME: LEE, CRYSTAL ANNE

PROJECT_TERMS: accurate diagnosis;Address;Affect;Benign;Cancer Patient;Child Support;Classification;Clinic;Clinical;clinical diagnosis;Clinical Management;Clinical Research;Clinical Treatment;clinically relevant;clinically significant;ClinVar;Communities;Comprehensive Health Care;Country;Databases;Dedications;Deposition;Diagnosis;diagnostic criteria;Diagnostic tests;Disease;Disease susceptibility;Ensure;Fostering;Foundations;Freckles;Funding;Funding Opportunities;gene panel;Genes;Genetic Predisposition to Disease;Genetic Risk;genetic testing;genetic variant;Genome;Genotype;Germ-Line Mutation;Goals;Guidelines;improved;Individual;Intellectual functioning disability;International;Journals;Laboratories;Legius syndrome;Literature;Malignant Neoplasms;Manuscripts;member;meningioma;Nervous System Disorder;Neurilemmoma;Neurofibromatoses;Neurofibromatosis 1;Neurofibromatosis 2;Neurofibromin 2;neurogenetics;NF1 gene;offspring;Oncogenes;Pathogenicity;Patient Representative;Patients;Peer Review;Persons;Phenotype;Philosophy;Predisposition;Prevalence;Procedures;Process;public database;Publishing;Recommendation;Reporting;Schwannomatosis;Series;Skin;SMARCB1 gene;Somatic Mutation;Standardization;Syndrome;Testing;tumor;Tumor Suppressor Proteins;United States National Institutes of Health;Update;Variant;variant of unknown significance;Work

PROJECT_TITLE: Neurofibromatosis and Schwannomatosis Genes Variant Curation Expert Panel (VCEP)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MGG-V (50)]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

ORG_STATE: FL

PHR: Project narrative Clostridioides difficile is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of life-threatening pseudomembranous colitis in the developed world, and is classified as ‘urgent threat’ by the Centers for Disease Control and Prevention (CDC). We propose to develop multivalent mucosal /parenteral vaccines against C. difficile infection (CDI).

PI_NAMEs: SUN, XINGMIN  (contact);WANG, SHIFENG

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Active Immunization;Adjuvant;Anaerobic Bacteria;Animal Model;Animals;anti-toxin;antibiotic-associated diarrhea;Antibiotics;Antibody Response;Antigens;Attenuated;Binding;Bioinformatics;C-terminal;Caspase;Cause of Death;Cells;Centers for Disease Control and Prevention (U.S.);Chemicals;Classification;Clinical Research;Clinical Trials;Clostridioides difficile vaccine;Clostridium difficile;Clostridium perfringens;Combined Vaccines;cross reactivity;Cytosol;Death Rate;Disease;disease transmission;dosage;enteric pathogen;Environment;Etiology;Exotoxins;Feces;Flagellin;Funding;Glucosyltransferase;Goals;Gut associated lymphoid tissue;Helicobacter pylori;Human;Immune;Immune response;Immunity;Immunization;Immunodominant Epitopes;Immunology;Individual;Infection;Influenza;Intestines;Intramuscular;Licensing;Life;Lipoproteins;M cell;Membrane Proteins;Morbidity - disease rate;mucosal vaccine;Mucous Membrane;Mus;Mycobacterium tuberculosis;N-terminal;novel;Oral;pathogen;Patients;prevent;Production;protective efficacy;Proteins;Pseudomembranous Colitis;receptor binding;Receptor Cell;Recurrence;Recurrent disease;Reproduction spores;Resistance;response;Route;Salmonella;Salmonella typhimurium;Salmonella Vaccines;single-cell RNA sequencing;Stomach;Structure;Symptoms;Tissues;Toxic effect;Toxin;Vaccine Adjuvant;vaccine candidate;vaccine development;vaccine efficacy;vaccine platform;Vaccines;vector;vector vaccine

PROJECT_TITLE: Multivalent vaccines against Clostridioides difficile infection

STUDY_SECTION: VID

STUDY_SECTION_NAME: Vaccines Against Infectious Diseases Study Section[VID]


NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Congenital Heart Disease;Heart Disease;Pediatric;Rare Diseases

ORG_CITY: BOSTON

PHR: In up to 3% of the population, the mitral valve, which allows the heart to pump blood forward to the body while preventing it from going backwards, becomes floppy and billows backwards when the heart contracts. One- third of patients with such floppy valves have abnormal cardiac beats that increase their risk for sudden cardiac death, and those complications are associated with scarring of the heart muscle in the region to which the valve is attached, with the mechanism of such scarring currently unknown and studies limited by lack of a disease model. Based on patient and experimental data and a novel model in which creating mitral valve prolapse causes localized scarring in previously normal hearts, we aim to discover how this scarring occurs and its relation to the stress induced by the valve on the wall of the heart, leading to new ways to preserve healthy heart muscle and prevent sudden cardiac death in this condition.

PI_NAMEs: LEVINE, ROBERT A (contact);NORRIS, RUSSELL

PROGRAM_OFFICER_NAME: EVANS, FRANK

PROJECT_TERMS: Affect;Arrhythmia;Benign;Biology;Biomechanics;Biopsy;blood pump;Cardiac;Cells;Cellular Stress;Cicatrix;Clinical;Collagen;Connexin 43;Contracts;coronary fibrosis;Data;Deposition;disease model;Electrophysiology (science);Event;experience;Fibroblasts;fibrogenesis;Fibrosis;Goals;Guidelines;Heart;Heart Abnormalities;heart rhythm;Histopathology;Image;Implant;improved outcome;In Vitro;in vivo;Individual;Infusion procedures;Interdisciplinary Study;Intervention;Isoproterenol;Left;Left atrial structure;Libraries;Link;Malignant - descriptor;Maps;Measures;mechanical force;mechanical stimulus;Mechanical Stress;Mechanics;Mitral Valve;Mitral Valve Insufficiency;Mitral Valve Prolapse;Modeling;Molecular;Monitor;mouse model;muscle stress;Myocardial;Myocardium;new therapeutic target;novel;Operative Surgical Procedures;Optics;Outcome;papillary muscle;Pathologic;Pathology;Pathway interactions;Patients;pharmacologic;Population;Predisposition;preservation;prevent;Production;Ptosis;Publications;repaired;Research;Risk;Role;sham surgery;Sheep;sheep model;Signal Pathway;Signal Transduction;Slice;Stress;Stretching;sudden cardiac death;Support Groups;Systole;Testing;Time;Tissues;Transducers;Ventricular;Ventricular Arrhythmia;Work

PROJECT_TITLE: Mechanism of Myocardial Fibrosis Induced by Mitral Valve Prolapse

STUDY_SECTION: TDPS

STUDY_SECTION_NAME: Therapeutic Development and Preclinical Studies Study Section[TDPS]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: RALEIGH

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

ORG_STATE: NC

PHR: Narrative: Deep vein thrombosis (DVT) affects two million Americans every year and can cause pulmonary embolism (PE), which is fatal in ~10% of acute cases, with higher rates in patients with cancer. Current DVT treatment techniques include systemic administration of thrombolytic drugs and endovascular catheter-based thrombectomy, which is either slow and/or carries risk of vessel damage. Our renewal proposal will develop an integrated dual-frequency catheter-accelerated sonothrombolysis system (iDUCAS), which can quickly and safely treat even the most advanced and heterogeneous clots and reduce the occurrence of complications, morbidity, and mortality of DVT.

PI_NAMEs: JIANG, XIAONING  (contact);XU, ZHEN

PROGRAM_OFFICER_NAME: GILLASPY, ALLISON

PROJECT_TERMS: Acceleration;Acoustics;Acute;Address;Affect;Age;Alteplase;American;Animal Model;Animals;Blood;Blood coagulation;California;Cardiology;Catheters;Clinical;clinical translation;clinically relevant;Coagulation Process;Contrast Media;Cytolysis;Deep Vein Thrombosis;design;Development;Disease;Dose;Evaluation;Family suidae;FDA approved;Feedback;Fibrinolytic Agents;Formulation;Frequencies;Goals;Grant;Hemorrhage;Hour;Image;image guided;imaging capabilities;improved;In Vitro;in vivo;in vivo evaluation;Injections;Institution;interest;Intervention;Legal patent;Licensing;Liquid substance;Malignant Neoplasms;Measures;Mechanics;Mediating;Michigan;Microbubbles;Modeling;Monitor;Morbidity - disease rate;mortality;Motion;Motor;multidisciplinary;nanoDroplet;nanometer;North Carolina;novel;novel strategies;Pathology;Patients;Performance;phase change;pre-clinical;pressure;Procedures;Process;Pulmonary Embolism;Research;Risk;Safety;Speed;System;Techniques;Technology;technology platform;Testing;Thrombectomy;thrombolysis;Thrombosis;Time;Tissues;tool;Torque;Transducers;translational impact;Ultrasonic Therapy;Ultrasonography;ultrasound;Validation;vaporization;Veins;Venous

PROJECT_TITLE: Integrated Dual-frequency Ultrasound Catheter for Accelerated Sonothrombolysis (iDUCAS)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ISB-N (03)]


ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer highly responsive to immune checkpoint blockade, suggesting a strong antitumor immune response. However, the immune cells contributing to antitumor activity in the tumor microenvironment of MCC are not well understood. This proposal will investigate whether tumor- infiltrating B cells, which have recently shown robust antitumor activity in several different cancer types, have antitumor activity in MCC.

PI_NAMEs: SCHNABEL, JULIA  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: adaptive immune response;Affect;anti-PD-1;anti-tumor immune response;Antibodies;Antibody Response;Antigens;Antitumor Response;Area;Automobile Driving;B-Cell Activation;B-Cell Neoplasm;B-cell receptor repertoire sequencing;B-Lymphocyte Subsets;B-Lymphocytes;Biopsy Specimen;cancer type;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Characteristics;Chemotactic Factors;cytokine;Data;Disease;Etiology;experimental study;Fluorescent Probes;Formalin;Frequencies;Genetic Transcription;Goals;Immune;immune activation;immune checkpoint blockade;immune system function;Immunity;Immunofluorescence Immunologic;Immunoglobulin G;Immunoglobulin Somatic Hypermutation;Immunoprecipitation;Immunotherapy;improved;Infiltration;Inflammatory;insight;interest;Investigation;Large T Antigen;Malignant Epithelial Cell;Malignant Neoplasms;Mass Spectrum Analysis;Merkel cell carcinoma;Merkel Cells;Mutation;Outcome;Paraffin Embedding;Patients;PD-1/PD-L1;Peptides;Polyomavirus;prognostic;Proteins;Recombinants;recruit;response;Role;Sampling;single-cell RNA sequencing;Skin Cancer;Slide;Small T Antigen;Solid Neoplasm;Specificity;Suspensions;T cell infiltration;T-Lymphocyte;tertiary lymphoid organ;Therapeutically Targetable;Tissue Embedding;tumor;Tumor Antigens;Tumor Immunity;tumor immunology;tumor microenvironment;tumor specificity;tumorigenesis;ultraviolet damage;Viral Antigens

PROJECT_TITLE: Understanding B cell immunity in Merkel cell carcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (20)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics;Lung;Lung Cancer;Orphan Drug;Precision Medicine;Rare Diseases

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE KRAS-driven non-small cell lung cancer (NSCLC) remains one of the most aggressive and lethal solid tumors. Therapeutic options and outcomes for NSCLC have remained virtually unchanged over the past thirty years. Using novel CRISPR/Cas9-based genome-engineering technologies we have established a unique and rapid research program to functionally characterize lung cancer mutations and identify genotype-specific metabolic vulnerabilities that can lead to novel therapeutic approaches in KRAS-driven lung cancer.

PI_NAMEs: PAPAGIANNAKOPOULOS, THALES  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Acceleration;Antioxidants;Cells;Clinical;Clinical Oncology;Consumption;CRISPR/Cas technology;Data;Dependence;enzyme pathway;Enzymes;Fructose;Genetic;Genetically Engineered Mouse;Genome engineering;Genotype;Glucose;Goals;Growth;Human;Image;Immunotherapy;inhibitor;KRAS2 gene;KRASG12D;loss of function;loss of function mutation;Lung Adenocarcinoma;Malignant neoplasm of lung;Malignant Neoplasms;Metabolic;Metabolism;Modeling;Molecular;mutant;Mutation;NADP;Neoplasm Metastasis;Non-Small-Cell Lung Carcinoma;novel;novel strategies;novel therapeutic intervention;Outcome;Pathway interactions;patient derived xenograft model;patient stratification;Patients;pharmacologic;polyol;pre-clinical;Pre-Clinical Model;precision medicine;Production;Prognosis;programs;Radiation;Regulation;Research;response;response biomarker;Solid Neoplasm;Sorbitol;standard of care;targeted treatment;Technology;Therapeutic;therapeutic target;transcription factor;treatment responders;tumor;tumor growth;tumorigenesis;virtual;Work

PROJECT_TITLE: Novel approaches to target KEAP1 mutant tumors

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Racial and Ethnic Minority Health Research;Rare Diseases;Stroke

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE Moyamoya disease (MMD) is a severe cerebrovascular condition with unknown cause and confers a high risk of stroke; although historically observed in individuals of East Asian ancestry, MMD is now being reported with increasing frequency in North America over a broader range of races and ethnicities. Stroke risk can be reduced when surgical revascularization procedures are performed, however, surgical response and disease trajectory can be highly variable, especially in the increasingly recognized North American phenotype. This work is focused on using novel neuroimaging methods, in combination with assessments of traditional stroke risk factors, at two of the largest MMD treatment centers to identify personalized signatures of brain tissue health that can be used to portend stroke risk, with the long-term goal of using this information to triage patients for appropriate and personalized surgical revascularization procedures.

PI_NAMEs: DONAHUE, MANUS J (contact);JORDAN, LORI CHAFFIN

PROGRAM_OFFICER_NAME: FARACO, CARLOS CESAR

PROJECT_TERMS: Academic Medical Centers;Address;adjudication;Admission activity;Adult;Affect;Age;American;Anemia;angiogenesis;Angiography;Animal Disease Models;Annual Reports;Asian ancestry;Asian Women;Awareness;Biological Markers;Black race;Blood Vessels;brain tissue;candidate marker;Cerebral Ischemia;Cerebrospinal Fluid;cerebrospinal fluid flow;cerebrovascular;Cerebrovascular Disorders;cerebrovascular reactivity;Cerebrum;Circulation;cognitive testing;Collaborations;Complication;Development;Diagnosis;Diagnostic Imaging;Digital Subtraction Angiography;Disease;East Asian;Equipment;Ethnic Origin;Etiology;Faculty;Feedback;Female;Frequencies;Goals;Health;hemodynamics;high risk;Hispanic;Hospitalization;Image;Impairment;improved;inclusion criteria;Individual;Indolent;Infrastructure;Internal carotid artery structure;Ischemia;Ischemic Stroke;Magnetic Resonance Imaging;male;Measurement;Medical;Metabolic;Methods;Motion;Moyamoya Disease;neuroimaging;neuroimaging marker;Neurologic;Neurologic Symptoms;Neurology;neurosurgery;new technology;Newly Diagnosed;North America;novel;Operative Surgical Procedures;Outcome;Outcome Measure;Participant;Pathogenesis;Pathway interactions;Patient Admission;Patient Triage;Patients;Pattern;Perfusion;personalized management;Phenotype;Physiology;Prevalence;Procedures;Production;prospective;Protocols documentation;Race;Radiology Specialty;Randomized;randomized trial;randomized, clinical trials;rare condition;Reaction Time;Reporting;Research Personnel;respiratory;response;revascularization;revascularization surgery;Risk;Risk Factors;Risk Management;sex;Site;Stress;Stroke;stroke risk;Structure of choroid plexus;success;surveillance imaging;symptomatology;Symptoms;Testing;Time;Tissues;tool;Transient Ischemic Attack;treatment center;treatment response;treatment trial;unethical;United States;Universities;Validation;Work

PROJECT_TITLE: Personalized hemodynamic and metabolic signatures of revascularization response in moyamoya disease

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Hematology;Human Genome;Immunotherapy;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

PHR: NARRATIVE Adoptive transfer of T cells that can recognize tumors and cause tumor cell death is a promising approach and has gained momentum after it was found that novel anti-tumor T cells could be engineered by viral transductions of tumor reactive T cell receptor (TCR), or chimeric antigen receptors (CAR). However, many confounding factors such as susceptibility to immunosuppression, or T cell's inability to persist and undergo activation induced cell death due to chronic antigen stimulation in a tumor microenvironment still persist. In this application, we propose to generate metabolically enhanced CD19-CAR-Ts based on our published methodology in Cell Metabolism and establish the issues of efficacy and toxicity in the phase 1B trial of this approach where targeting immunometabolism to program CAR-Ts could be used in future trials to treat a large umbrella of non-Hodgkin Lymphoma patients.

PI_NAMEs: HESS, BRIAN  (contact);MEHROTRA, SHIKHAR

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Accreditation;Address;Adopted;Adoptive Cell Transfers;Adrenal Cortex Hormones;Adverse effects;Affect;Aftercare;Antigens;Antitumor Response;B-Cell NonHodgkins Lymphoma;CAR T cell therapy;CD19 gene;CD28 gene;CD34 gene;CD8-Positive T-Lymphocytes;Cell Count;Cell Death;Cell Death Induction;Cell Survival;Cell Therapy;Cells;Cellular Metabolic Process;Chicago;chimeric antigen receptor;chimeric antigen receptor T cells;Chronic;Chronic Lymphocytic Leukemia;Clinical;Clinical Trials;commercialization;Coupled;cytokine;cytokine release syndrome;Cytoplasm;Data;design;Development;Disease Progression;Disease remission;Dose;effector T cell;efficacy evaluation;Engineering;Enrollment;Ensure;Environment;Epigenetic Process;Exhibits;Exposure to;Failure;FDA approved;Future;Genetic Engineering;Hybrids;IL17 gene;Immune;immune effector cell-associated neurotoxicity syndrome;Immunosuppression;Immunotherapy;improved;in vivo;Incidence;Indolent;Infusion procedures;Lead;Leukapheresis;Life;Malignant Neoplasms;manufacture;Memory;Metabolic;metabolic fitness;Methodology;Molecular Biology;Molecular Profiling;Mus;neoplastic cell;Non-Hodgkin's Lymphoma;non-Hodgkin's lymphoma patients;novel;Outcome;Patients;Phase;Phase I Clinical Trials;Phase Ib Trial;Phenotype;PPBP gene;pre-clinical;Predisposition;programs;Progression-Free Survivals;Publications;Publishing;Recommendation;Recurrent disease;Refractory;Relapse;Research;response;Risk;Safety;single cell sequencing;Small-Cell Lymphoma;stemness;Sterility;success;T cell response;T cell therapy;T-Cell Receptor;T-Lymphocyte;Th1 Cells;Therapeutic;Therapy trial;Toxic effect;transcriptome sequencing;Translating;tumor;Tumor Antigens;tumor growth;tumor microenvironment;Universities;validation studies;vector;Viral

PROJECT_TITLE: Assessing Metabolically Reprogrammed and Purified CD19-CAR-T in NHL and CLL

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

ORG_CITY: LINCOLN

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF NEBRASKA LINCOLN

ORG_STATE: NE

PHR: NARRATIVE The goal of the proposed research project is to design a new type of orally administered particle system capable of delivering DNA to the intestines for use as a gene therapy (e.g., to treat inflammatory bowel diseases) or a vaccine. These particles will be made using vesicles produced by non-pathogenic bacteria found in a healthy gut. The proposed delivery platform could improve DNA delivery to bring orally delivered, DNA-based medicines to the clinic.

PI_NAMEs: PANNIER, ANGELA K (contact);RAMER-TAIT, AMANDA ELLEN

PROGRAM_OFFICER_NAME: KANG, KIHWA

PROJECT_TERMS: 2019-nCoV;Affect;Anti-Inflammatory Agents;Award;Bacteria;Biocompatible Materials;Biological;Biological Assay;Biology;Blood Circulation;Caco-2 Cells;Cell Survival;Cells;Chromosome Mapping;Clinic;Collaborations;Collection;Colon Carcinoma;Communication;cytokine;cytotoxicity;Data;Defect;delivery vehicle;design;Development;Diabetes Mellitus;Disease;DNA;DNA delivery;Dose;Electron Microscopy;Electroporation;Environment;Epithelial Cells;Escherichia coli;exosome;Exposure to;Fluorescence;Funding Opportunities;Gastrointestinal Diseases;Gastrointestinal tract structure;Gastrointestinal Transit;Gene Delivery;gene therapy;Genes;Goals;gut bacteria;gut microbiota;Hemophilia A;Human;Immunity;immunoregulation;improved;In Vitro;in vivo;in vivo evaluation;Inflammatory Bowel Diseases;Inflammatory Response Pathway;intestinal epithelium;Intestines;Laboratories;lead candidate;Libraries;Macrophage;Mammalian Cell;Marketing;Mediating;Medicine;Membrane;Metabolic;Methods;Microbiology;Morphology;Mucosal Immunity;Mucous Membrane;Mus;nanocarrier;nanoparticle;nanovesicle;Nature;non-viral gene delivery;novel;Nutritional;Oral;Oral Administration;Outcome;particle;Patient Compliance;plasmid DNA;prevent;Production;Property;Proteins;Research Project Grants;response;Route;Stomach;success;System;Systemic Therapy;Techniques;Technology;Testing;Therapeutic;therapeutic gene;therapy outcome;Tissues;Transfection;transgene expression;Transgenes;Translational Research;uptake;Vaccinated;Vaccination;vaccination strategy;Vaccines;Vascularization;Vesicle;Work

PROJECT_TITLE: Developing Outer Membranes Vesicles from Commensal Gut Bacteria as an Oral Gene Delivery Platform

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-X (83)]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Congenital Structural Anomalies;Genetics;Human Genome;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative Infantile hemangioma, a benign vascular tumor that occurs in 4-5% of children, is treated with propranolol, yet why and how propranolol is effective has remained a mystery. We have new data that uncovers a novel, unexpected mechanism downstream of propranolol that involves cholesterol metabolism. In this proposal we will deeply study how propranolol and statins reduce vascular overgrowth in infantile hemangioma with the goal of improving treatment options for infantile hemangioma, and potentially other diseases where vascular overgrowth occurs.

PI_NAMEs: BISCHOFF, JOYCE E. (contact)

PROGRAM_OFFICER_NAME: GALIS, ZORINA S

PROJECT_TERMS: Anabolism;Area;ATAC-seq;Atenolol;base editing;Benign;beta-adrenergic receptor;Binding;Biological Process;Blood Vessels;Breathing;Cells;Child;ChIP-seq;Cholesterol;Cholesterol Homeostasis;Chromatin;Clinical;Clinical Management;Clinical Research;cohort;Coupled;Data;Data Set;diagnostic tool;Drug Modulation;drug repurposing;drug-sensitive;effective therapy;enantiomer;Endothelial Cells;endothelial stem cell;Endothelium;Enhancers;Enzymes;Equation;Etiology;Face;farnesyl pyrophosphate;Farnesyl Transferase Inhibitor;feeding;Foundations;Funding;Gene Expression Profiling;gene regulatory network;gene repression;Genes;Genetic Transcription;genetic variant;Genome;genome editing;Genomics;Goals;Growth;Hemangioma;Human;Implant;improved;in vitro activity;in vivo;Infant;inhibitor;isoprenoid;Link;Location;matrigel;Mediating;Medical;mevalonate;Molecular;Molecular Probes;Molecular Target;Mus;Neoplasms in Vascular Tissue;novel;Nucleic Acid Regulatory Sequences;Operative Surgical Procedures;Outcome;Oxidoreductase;Pathologic;Pathway interactions;Patients;pre-clinical;Pre-Clinical Model;prenylation;prevent;Process;Propranolol;protein expression;Protein Isoprenylation;Reporter;Research;response;Risk;side effect;Signaling Molecule;single-cell RNA sequencing;small molecule;small molecule inhibitor;SOX18 gene;stem cell differentiation;stem cells;stemness;Strawberry nevus;Structure;Surveys;Testing;Therapeutic;Tipifarnib;transcription factor;transcriptome sequencing;transcriptomics;treatment response;Validation;Variant;Vascular Diseases;Vasculogenic;Visual impairment;Xenograft Model

PROJECT_TITLE: Blood vessel assembly from multipotent hemangioma-derived stem cells

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


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

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Narrative In the early stages of Alzheimer’s disease (AD), entorhinal cortex connections with hippocampal CA1 emerges as a primary neural circuit that undergoes significant neurodegenerative change, but the cell type specific connections and their susceptibility remains unclear. Here, we will use advanced viral labeling strategies in an AD mouse model to identify vulnerable CA1 projection cell types and characterize their morphological neurodegenerative changes to AD. After identifying CA1 structural vulnerabilities, we will use MERFISH spatial transcriptomics to investigate the changes to AD-relevant gene expression within these vulnerable neurons and characterize the molecular changes that are associated with AD neurodegeneration.

PI_NAMEs: PACHICANO, MARICARMEN  (contact)

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: 3-Dimensional;abeta accumulation;Affect;aged;Alzheimer's Disease;Alzheimer's disease pathology;Amyloid;Amyloid beta-Protein;Anatomy;Automobile Driving;Brain;Brain region;Categories;Cell Death;Cell Physiology;cell type;Cells;cellular pathology;Characteristics;Classification;Communication;Complex;Cytoskeleton;Data;design;Deterioration;Development;Disease;Disease Progression;Down-Regulation;drug development;Early treatment;entorhinal cortex;experimental study;Extracellular Space;falls;Gene Expression;Genes;Goals;Hippocampus;hyperphosphorylated tau;Impaired cognition;In Situ Hybridization;Individual;Injections;insight;Intervention;Investigation;Label;Lead;Measures;medial temporal lobe;Memory;Memory impairment;memory process;Methodology;Methods;microscopic imaging;Microscopy;mild cognitive impairment;Molecular;molecular pathology;Morphology;mouse model;Mus;Nerve Degeneration;neural circuit;Neurodegenerative Disorders;Neurofibrillary Tangles;neuroimaging;neuron loss;neuronal circuitry;Neurons;novel;Output;Pathologic;Pathology;Pathway interactions;Pattern;Play;Population;postsynaptic;Predisposition;presynaptic;Process;reconstruction;response;Retrieval;Risk;Role;Senile Plaques;Structure;Synapses;targeted treatment;tau Proteins;Taxonomy;Techniques;Technology;Therapeutic Intervention;Thick;transcription factor;transcriptomics;Up-Regulation;Viral;Work

PROJECT_TITLE: CA1 cell-type susceptibility in Alzheimer's


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

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Narrative The proposed research is designed to understand the neuronal circuits that control posture (standing) after spinal cord injury. We use novel transgenic, electrophysiological and rehabilitation methods to target propriospinal neurons that promote motor function after injury. Once successfully developed in our animal preparations, these methods can be adapted to human subjects with spinal cord injury, allowing the possibility of new therapies for recovery of function after spinal cord injury.

PI_NAMEs: BENNETT, DAVID JAMES;HECKMAN, CHARLES  (contact);MANUEL, MARIN

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Acute;Adult;Anatomy;Animals;awake;Bilateral;Bypass;central pattern generator;Chronic;Cutaneous;Data;Decerebration procedure;design;Electrophysiology (science);Excitatory Postsynaptic Potentials;Exhibits;experimental study;Extensor;Felis catus;Hindlimb;human subject;In Vitro;Injury;kinematics;Limb structure;Measures;Methods;Motor;Motor Neurons;Movement;Mus;Muscle;Musculoskeletal Equilibrium;Nerve;neuronal circuitry;Neurons;Neurostimulation procedures of spinal cord tissue;novel;novel therapeutics;optogenetics;Output;Paralysed;Periodicity;Phase;Posture;Preparation;prevent;Property;Recovery;Recovery of Function;Recurrence;Rehabilitation therapy;Research;Residual state;Role;Secure;Sensory;sensory feedback;Sodium;Spasm;Spinal;Spinal Cord;Spinal cord injury;Surveys;sustained recovery;Testing;Training;transcription factor;Transgenic Organisms;treadmill;treadmill training;V3 neuron;voltage;Walking;Weight-Bearing state;Wheelchairs

PROJECT_TITLE: The role of propriospinal neurons in the recovery of posture after spinal cord injury

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CN-T (02)]


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative The aim of this study is to develop an efficient and sensitive system for delivering and detecting multiple molecules, with the objective of understanding the roles of extracellular vesicles in cellular processes and facilitating their widespread use in research and therapy. The proposed system will simplify the labor-intensive and challenging procedures involved in vesicular loading and cargo quantification by integrating a high-throughput particle manipulation technique, physical molecular delivery mechanism, and single-molecule detection technique into a user-friendly device. By providing ease of operation and a streamlined workflow, this approach will offer a systematic and standardized method for manipulating, characterizing, and classifying extracellular vesicles based on their origins, properties, and functions.

PI_NAMEs: HUR, SOOJUNG CLAIRE (contact)

PROJECT_TERMS: Area;Basic Science;Biological Assay;Biological Process;biological research;Biology;cancer cell;Cancer cell line;Cell Communication;Cell Physiology;Cell Reprogramming;Cells;Classification;Clinical;clinical application;Clinical Research;Complex;Coupled;Detection;detection method;detection platform;Development;Devices;Diagnostic;diagnostic biomarker;Disease;Electrodes;Electroporation;Ensure;exosome;extracellular vesicles;fluorophore;Frequencies;Gene Expression Regulation;Horizontal Gene Transfer;Individual;innovation;intercellular communication;Lasers;Lighting;Liposomes;Measurement;Mediating;Medicine;Membrane;Membrane Proteins;Methods;Microfluidic Microchips;Microfluidics;MicroRNAs;Microspheres;Molecular;Molecular Profiling;nanoscale;novel diagnostics;novel therapeutic intervention;Oncogenic;operation;Optics;particle;Pathologic;Pathologic Processes;Pattern;Phenotype;Physiological;Physiological Processes;Play;Preparation;preservation;Procedures;Process;Production;Property;Regulation;Reproducibility;Research;Resolution;Role;segregation;single molecule;Sorting;Source;Spectrum Analysis;Spinal;Standardization;submicron;Surface;System;targeted treatment;Techniques;Therapeutic;Translational Research;Translations;user-friendly;Vesicle

PROJECT_TITLE: STEADI:System for Translational Exosome Analysis and Diagnostics through Integrating electroporation and single-molecule detection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-M (82)]


NIH_SPENDING_CATS: American Indian or Alaska Native;Bioengineering;Biotechnology;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative The proposed work aims to establish the Humanity Unlocking Biomaterials (HUB), a coordinating center that addresses the disconnectedness among biomaterials researchers and emerging disciplines, such as computational modeling and artificial intelligence, to unlock the full potential of biomaterials-based technologies. By creating a diverse community, providing accessible resources and funding opportunities, and fostering cross- disciplinary collaboration, the HUB seeks to revolutionize biomaterials translation and produce innovative technologies for biomedical applications. The HUB aims to significantly improve human health and save lives impacted by various diseases through this initiative.

PI_NAMEs: ENIOLA-ADEFESO, OMOLOLA  (contact);STEVENS, KELLY R

PROGRAM_OFFICER_NAME: RUSSELL, LUISA MARIE

PROJECT_TERMS: Academy;Acceleration;Address;Artificial Intelligence;Biocompatible Materials;Biomedical Engineering;Biomedical Technology;Cardiovascular Diseases;career;Cementation;Clinical;clinical application;clinical translation;Collaborations;commercialization;Communities;community engagement;Complex;Computer Models;Computer Simulation;Coordination and Collaboration;Country;Crystallization;Development;Discipline;Disease;Education;Education and Outreach;education resources;Engineering;Ensure;experience;Faculty;Fostering;Funding;Funding Opportunities;Generations;Harvest;Health;Hispanic-serving Institution;Human;Humanities;Hydrogels;improved;Indian reservation;Inflammatory;Infrastructure;innovation;innovative technologies;Institution;Leadership;Malignant Neoplasms;Medical;meetings;member;National Institute of Biomedical Imaging and Bioengineering;Native Americans;Neurodegenerative Disorders;Organoids;outreach;podcast;power harvesting;Productivity;programs;Publications;Rare Diseases;rational design;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;Scientist;Series;success;symposium;synthetic protein;Technology;technology development;Technology Transfer;Translations;tribal lands;Universities;virtual;Voice;web site;Work;working group;Yakama Indian

PROJECT_TITLE: Humanity Unlocking Biomaterials (HUB)  Coordinating Center

STUDY_SECTION_NAME: Special Emphasis Panel[ZEB1 OSR-E (J2)]


NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Immunotherapy

ORG_CITY: Rockville

ORG_NAME: FEDERATION OF AMER SOC FOR EXPER BIOLOGY

PHR: NARRATIVE Ion channels have a critical role in all cell types and organs but our understanding of their function in the immune system and their role in physiological and pathological immune responses is in its nascent stages. This proposal requests funds to support the first FASEB Science Research Conference (SRC) on the topic of "Channels and Transporters in Immunity" from 14–20th June 2024. The overall goal of this SRC is to establish a recurring venue where immunologists, physiologists, and translational scientists can interact, discuss and collaborate in this burgeoning area of research, advance new therapeutic strategies and enhance the career-development of trainees and junior faculty, especially those from underepresented minorities.

PI_NAMEs: FESKE, STEFAN  (contact)

PROGRAM_OFFICER_NAME: BARTELS, ADELINA EWURA-ABENA

PROJECT_TERMS: adaptive immunity;Advisory Committees;Anxiety;Area;Arrhythmia;Asthma;Autoimmune Diseases;Autoimmunity;Basic Science;Biophysics;Cardiovascular system;career development;cell type;Cells;Cellular biology;Clinical;clinical application;Collaborations;Communities;cost;Dedications;demographics;design;Development;Disabled Persons;Disease;drug discovery;Drug Targeting;Epilepsy;Event;Faculty;FDA approved;Female;frontier;Funding;Genes;Goals;Human;Hypersensitivity;Hypertension;Immune;Immune response;Immune system;Immune System Diseases;Immunity;immunodeficiency;Immunologics;Immunologist;Immunology;immunomodulatory therapies;immunoregulation;Infection;Inflammation;Inflammatory Response;innovation;interdisciplinary collaboration;interest;Ion Channel;Ions;Knowledge;Language;Link;male;Malignant Neoplasms;meetings;Metabolism;Methods;Minority;Minority Groups;Modernization;Mutation;Myelogenous;Natural Immunity;neglect;Nervous System;Neurodegenerative Disorders;neuroinflammation;novel;novel therapeutic intervention;Organ;Pain;Participant;pathogen;Pathologic;Patients;Persons;Phagocytes;pharmacologic;Pharmacologic Substance;Physiological;Physiology;Population;Postdoctoral Fellow;posters;pre-clinical;preclinical study;Recording of previous events;Recurrence;Regulation;Request for Proposals;Research;Role;Schedule;Science;Scientist;Sepsis;Series;Shapes;Signal Transduction;Stimulus;structural biology;Students;success;symposium;targeted treatment;Techniques;Therapeutic;Tissues;Translating;translational approach;translational scientist;Translations;Transmembrane Transport;Tumor Immunity;Underrepresented Minority;virtual;Woman;zinc-binding protein

PROJECT_TITLE: Channels and Transporters in Immunity

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 LK-D (J1)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: PROJECT NARRATIVE This proposal intends to study the role of microRNAs (miRs) contained in the exosomes of Natural Killer (NK) cells in the cytotoxic activity of these vesicles against neuroblastoma (NB) and in their ability to synergize with chemoimmunotherapy. The study will identify the mechanism through which aNK-derived exosomal miRs elicit a cytotoxic effect on NB cells, will explore this mechanism to increase efficacy of current chemoimmunotherapy for the treatment of NB, and will correlate circulating and exosomal miRs to response to chemoimmunotherapy. The results of this study will help identify new strategies to treat NB (and possibly other types of cancer) and will ultimately lead to increased number of saved lives of cancer patients.

PI_NAMEs: ASGHARZADEH, SHAHAB ;FABBRI, MULLER  (contact)

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: Activated Natural Killer Cell;Affect;Antibodies;antibody-dependent cell cytotoxicity;Antigen-Presenting Cells;antitumor effect;aurora kinase A;Biological Markers;Biology;Blood;Blood specimen;cancer cell;Cancer Patient;cancer type;Cell Line;cell type;Cell-Mediated Cytolysis;Cells;chemotherapy;Child;Clinical;cohort;Combined Modality Therapy;cranium;cytotoxic;cytotoxicity;Data;Development;Diagnosis;Disease;DNA;Economic Burden;Emotional;Engineering;exosome;experimental study;extracellular vesicles;Family;Friends;functional loss;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Grant;Granulocyte-Macrophage Colony-Stimulating Factor;Hand;high risk;Human;Immuno-Chemotherapy;Immunotherapeutic agent;Immunotherapy;improved;improved outcome;Interleukin-15;Interleukin-2;K-562;Life;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Messenger RNA;MicroRNAs;Modeling;MYCN gene;nanoparticle;Natural Killer Cell Immunotherapy;Natural Killer Cell toxicity;Natural Killer Cells;NCAM1 gene;Neuroblastoma;neuroblastoma cell;Newly Diagnosed;novel;Pathway interactions;patient response;patient stratification;Patient-Focused Outcomes;Patients;Pediatric Neoplasm;Pediatric Oncology Group;Phase;Plasma;Play;Prognostic Marker;Proteins;Protocols documentation;receptor;Refractory;Regimen;Relapse;Resistance;response;response biomarker;RNA;Role;Sampling;sialogangliosides;social;Solid;Survival Rate;synergism;Testing;TGFBR1 gene;TGFBR2 gene;Therapeutic;therapeutically effective;therapy outcome;transcriptome sequencing;Transforming Growth Factor beta;Treatment Efficacy;tumor;tumor microenvironment;Untranslated RNA;Up-Regulation;Vesicle;weapons;Whole Blood

PROJECT_TITLE: Clinical Implications of Natural Killer-derived exosomal miRNAs in Neuroblastoma