NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Neurosciences

ORG_CITY: AMHERST

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: The proposed research will develop a non-invasive, challenge-free, widely available imaging method to map cerebral oxygen extraction fraction (OEF), a direct biomarker for tissue viability and essential for patient care strategies. Successful development will lead to easily and widely usable tool for quantitative mapping of OEF, which can be routinely used on all 3T MRI scanners to study brain functions and neurologic disorders including stroke.

PI_NAMEs: CHO, JUNGHUN  (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Adult;Algorithms;Alzheimer's Disease;Blood;blood oxygen level dependent;Blood Vessels;Brain;Brain Ischemia;Brain Mapping;Brain Neoplasms;brain tissue;Calibration;cerebral atrophy;Cerebral Neoplasm;Cerebrum;clinic ready;Clinical;clinical practice;Complex;computerized data processing;Consumption;Data;data acquisition;deep learning;Dependence;Development;Disease;Elderly;Ensure;experience;Formulation;Functional Magnetic Resonance Imaging;Future;Gases;Half-Life;Hour;Hypoxia;Image;imaging modality;improved;Infarction;Inhalation;Injections;Institution;Intracranial Arterial Stenosis;Iron;Ischemia;Ischemic Stroke;Magnetic Resonance Imaging;Magnetism;Maps;Measures;Metabolism;Methods;Modeling;Multiple Sclerosis;neglect;Nervous System Disorder;neurovascular;new technology;Noise;novel;Oxygen;Participant;Patient Care;Patients;Phase;Positron-Emission Tomography;Predisposition;Property;quantitative imaging;radioligand;Reference Standards;Research;Sampling;Scheme;Severity of illness;Signal Transduction;simulation;Site;Source;Speed;Stroke;Techniques;Time;tissue biomarkers;Tissue Viability;Tissues;tool;Tracer;treatment stratification;usability;Validation;Venous;venule;Visit;Weight

PROJECT_TITLE: Development and Validation of MRI Mapping of Brain Oxygen Metabolism for Clinical Use

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


ADMINISTERING_IC: EY

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Eye Disease and Disorders of Vision;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OPHTHALMOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE To preserve sight, glaucoma patients must take the eye drops recommended by their doctor. And yet, 80% of patients do not consistently take their medications. The Support, Educate, Empower Personalized Glaucoma Coaching Trial will test whether evidence-based individualized education and counseling improves medication adherence compared to standard care.

PI_NAMEs: NEWMAN-CASEY, PAULA ANNE (contact)

PROGRAM_OFFICER_NAME: EVERETT, DONALD F

PROJECT_TERMS: Address;Adherence;Adult;African American;African American population;Behavior;behavior change;blind;Blindness;Caring;Characteristics;Clinic;Clinical;Clinical Practice Guideline;Communication;comparative efficacy;Competence;Consolidated Framework for Implementation Research;cost;Counseling;Data;Diabetes Mellitus;Diagnosis;Disease;Disparity;Distress;Dose;Economically Deprived Population;Economics;Education;effective therapy;Effectiveness of Interventions;eHealth;Electronics;empowerment;Enrollment;Evaluation;evidence base;experience;Eyedrops;Focus Groups;Funding;Future;Glaucoma;Goals;Health behavior;Health Educators;Health Personnel;High Prevalence;implementation facilitators;implementation intervention;implementation study;improved;Income;Intervention;intervention participants;Low income;low socioeconomic status;Mediating;Mediator;medication compliance;Methods;Minority Groups;Modeling;Monitor;Motivation;motivational enhancement therapy;National Eye Institute;novel;Outcome;outreach;Participant;participant interview;Patients;Persons;Pharmaceutical Preparations;Physicians;Physiologic Intraocular Pressure;Pilot Projects;preference;preservation;programs;Provider;psychologic;Psychosocial Influences;Race;racial disparity;randomized, clinical trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;recruit;Reminder Systems;Research;Sampling;satisfaction;Self Determination;Self Management;Shapes;skills;social disparities;sociodemographics;socioeconomic disparity;standard care;Surveys;Technology;Telephone;Test Result;Testing;Text;theories;Time;tool;Training;Trust;Vision;Visual;Work

PROJECT_TITLE: Support, Educate, Empower: The SEE Personalized Glaucoma Coaching Trial

STUDY_SECTION: BMIO

STUDY_SECTION_NAME: Behavioral Medicine, Interventions and Outcomes Study Section[BMIO]


ADMINISTERING_IC: NS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Neurodegenerative;Neurosciences;Physical Activity;Physical Rehabilitation;Rehabilitation

ORG_CITY: NEW YORK

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Balance and aerobic training show promise as treatments for degenerative cerebellar diseases, but the neural effects of both training methods are unknown. The goal of this project is to evaluate how each training method impacts the brain, and particularly, the degenerating cerebellum. Various neuroimaging techniques will be used to accomplish this goal and test our hypothesis that balance training impacts brain structures outside the cerebellum whereas aerobic training causes more neuroplastic changes within the cerebellum.

PI_NAMEs: BARBUTO, SCOTT  (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Aerobic;Aerobic Exercise;Affect;Animals;Area;Ataxia;Back;Balance training;Brain;Brain scan;career;career development;Cerebellar degeneration;Cerebellar Diseases;Cerebellum;Cessation of life;Clinical;Clinical Research;clinically significant;Compensation;Data;Dendrites;Diagnosis;Diffusion Magnetic Resonance Imaging;disability;Disease;Disease Progression;Doctor of Philosophy;effective therapy;Equilibrium;Exercise;exercise training;functional MRI scan;Future;Goals;gray matter;Home;Immunology;improved;Individual;Inherited;interest;K-Series Research Career Programs;Learning;Locomotion;Master of Science;Measures;Mentors;Methods;Motor Cortex;Motor Skills;Movement Disorders;MRI Scans;multidisciplinary;neural;neuroimaging;Neurologic Examination;Neurologic Signs;Neuronal Plasticity;Participant;Persons;Pharmaceutical Preparations;Physical Medicine;Physical Rehabilitation;Population;programs;Public Health;Randomized;Recommendation;Regimen;Research;Research Design;Research Personnel;Research Project Grants;Research Support;responsible research conduct;Rest;sedentary;skills;Spinocerebellar Ataxias;Spinocerebellar Degenerations;Statistical Data Interpretation;Statistical Methods;Structure;symptomatic improvement;Synapses;Techniques;Testing;Training;Training Programs;United States National Institutes of Health;Wheelchairs;Work

PROJECT_TITLE: The Neural Effects of Balance Versus Aerobic Training in Individuals with Degenerative Cerebellar Diseases

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Patient Safety;Precision Medicine

ORG_DEPT: PHARMACOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Narrative The inability to predict cardiovascular activity of compounds has lead to numerous drug failures. This project aims to decipher links between drug signature, structure, and cardiovascular activity through the application of cell based experiments, bioinformatics, and machine learning to genomic information. The resulting validated methods will broaden our understanding of the role of pharmacogenomics in drug development and provide a novel approach to cardiovascular activity prediction.

PI_NAMEs: ZATORSKI, NICOLE  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Address;Adverse reactions;Age;Amino Acid Sequence;Biochemical;Bioinformatics;Biological;Biological Assay;Biological Phenomena;Biological Process;biological systems;Cardiotoxicity;Cardiovascular Agents;Cardiovascular system;career;Cell Physiology;Cells;Chemical Structure;Collaborations;cost;Data;Databases;Development;Disease;Drug Approval;drug development;drug structure;Drug toxicity;drug withdrawal;Environment;experience;experimental study;Failure;Future;Gene Expression;Gene Expression Profile;gene function;Genes;Genomics;Genotype;Goals;Graph;Health;Human;improved;Informatics;insight;Laboratories;Lead;Learning;learning algorithm;Life;Link;Machine Learning;Maps;Marketing;Mentorship;Messenger RNA;Methods;Molecular;next generation;novel strategies;novel therapeutics;Patients;Pattern;personalized medicine;Pharmaceutical Preparations;Pharmacogenomics;Physicians;Play;predictive tools;Process;Program Development;programs;protein folding;protein function;protein structure;Proteins;Proteome;Protocols documentation;Reaction;Reproducibility;Research;Research Personnel;response;Role;Sampling;Scientific Inquiry;Scientist;skills;strength training;Structural Genes;Structure;Technology;Therapeutic;Thinking;three dimensional structure;Time;tool;Toxic effect;Training;training data;Transcript;transcriptomics;web server;Withdrawal;Work

PROJECT_TITLE: Compound Cardiovascular Activity Prediction Using Structural and Genomic Features


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Immunization;Infectious Diseases;Lung;Prevention;Vaccine Related

ORG_CITY: SEATTLE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative This project will develop new Covid-19 therapeutics for infected patients and to protect caregiver and susceptible populations. The therapeutics are designed for nebulizer and mass-distributable inhalation devices to respond rapidly against COVID-19 outbreaks and future coronavirus threats.

PI_NAMEs: STAYTON, PATRICK S. (contact)

PROGRAM_OFFICER_NAME: BASU, DIPANWITA

PROJECT_TERMS: 2019-nCoV;alveolar epithelium;Alveolar Macrophages;Alveolus;Anti-Inflammatory Agents;Anti-viral Agents;Antibiotics;Antimicrobial Resistance;antiviral drug development;Azithromycin;bacterial resistance;Biological Availability;Biomedical Engineering;Burkholderia pseudomallei;Caregivers;Cells;Cessation of life;Clinical;clinical development;Coronavirus;Coronavirus Infections;coronavirus therapeutics;COVID-19;COVID-19 outbreak;COVID-19 pandemic;COVID-19 therapeutics;COVID-19 vaccine;Crowding;density;design;Development;Diffusion;Disadvantaged;Disease;disease model;Disparity population;Dose;Doxycycline;drug candidate;Drug Combinations;drug isolation;Drug Kinetics;Drug resistance;Drug Targeting;Effectiveness;Enzymes;Epithelial Cells;Epithelium;Evolution;Exhibits;experience;Formulation;Future;future pandemic;Gap Junctions;Histologic;Hospitalization;Hospitals;Human;improved;Individual;Inflammatory Response;Inhalation;Inhalation Device;Inhalation Drug Administration;Inhalation Therapy;Intensive Care;Lead;Leadership;Life;Ligands;liquid chromatography mass spectrometry;Lung;Lung infections;lung pathogen;Macrophage;Mannose;manufacture;manufacturing scale-up;Mediating;Melioidosis;Methods;Modality;Modeling;monomer;mouse model;Nebulizer;novel vaccines;Oral;Organ;pandemic potential;pathogen;Patients;Peptides;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;polymerization;Polymers;Population;Positioning Attribute;preclinical development;Predisposition;Procedures;Prodrugs;Property;prophylactic;pulmonary agents;Pulmonology;remdesivir;Research Personnel;Resistance;Resource-limited setting;response;Rodent Diseases;Rodent Model;Safety;SARS-CoV-2 variant;Schedule;Solubility;Source;Structure;Testing;Therapeutic;Time;Toxic effect;Tularemia;unvaccinated;uptake;Vaccination;Vaccines;Variant;Viral;viral entry inhibitor;Viral Load result;Viral reservoir;Work

PROJECT_TITLE: Inhalation Therapy Platform for Coronavirus Infection Treatment

STUDY_SECTION: GDD

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


ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Pathological angiogenesis is a process that is the underlying factor in several conditions and diseases which include, but are not limited to cancer, skin diseases, age-related blindness, diabetic ulcers, cardiovascular disease and diabetic ulcers. The rate at which men and women develop these conditions and their response to treatments for these conditions varies. I am proposing this project to investigate why these contrasting responses exist and aim to offer an explanation as to why and how IgG1 antibodies may be used as a cheaper and alternative therapeutic agent to positively affect outcomes of these type of diseases processes.

PI_NAMEs: ARGYLE, DIONNE ALEXIS (contact)

PROJECT_TERMS: Address;Adult;Affect;Affinity;age related;Age related macular degeneration;angiogenesis;Angiogenesis Inhibition;Angiogenesis Inhibitors;Animal Model;Animals;Antibodies;antigen binding;Antigens;Arthritis;Beds;Binding;Biochemical;Biological Assay;Biological Models;Birth;Blindness;Blood Vessels;Bone Marrow;Cardiovascular Diseases;Categories;CBL gene;Cell model;Cells;Characteristics;Chemotaxis;Code;Coronary Arteriosclerosis;diabetic ulcer;Disease;Disparity;Equilibrium;Estrogens;Exhibits;Exudative age-related macular degeneration;Fc domain;Fc Receptor;Female;Genes;Germ Cells;Goals;Guidelines;Heart failure;helicase;Homeostasis;Hormonal;Human;human male;IgG Receptors;improved;Incidence;Inflammatory Bowel Diseases;Intervention;Ischemic Stroke;knockout gene;Knowledge;Link;Macrophage;male;Malignant Neoplasms;Mediating;Mediator;Medical;men;Modeling;Molecular;mouse model;Mus;Outcome;Pathogenesis;Pathologic Neovascularization;Pathway interactions;Pattern;Peripheral arterial disease;personalized approach;Phosphorylation;Physiological;Play;Policies;Process;Proteins;Publishing;receptor;Regulation;Reporting;Research;response;Risk Factors;Role;Severities;sex;sex as a biological variable;Sex Bias;Sex Chromosomes;Sex Differences;sex disparity;sexual dimorphism;Signal Transduction;skin disorder;Solid Neoplasm;Testing;Testosterone;Therapeutic Agents;therapy outcome;Tissues;Transgenes;treatment response;Ubiquitination;United States National Institutes of Health;vascular abnormality;Vascular Endothelial Growth Factor Receptor-1;Vascular remodeling;Woman;Y Chromosome

PROJECT_TITLE: Sexual dimorphism in antigen-independent angiogenesis inhibition of IgG1 antibodies


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: DALLAS

ORG_DEPT: PATHOLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE This study investigates the mechanisms by which the gut microbiota influences brain metastasis outgrowth. The specific aims of this project will evaluate the impact and functional significance of gut-derived signaling molecules in brain metastasis outgrowth and cross-talk of brain-resident myeloid cells with peripherally-derived myeloid and T lymphocytes. Furthermore, this study will also assess a clinically applicable therapeutic strategy combining microbiota modulation and immunotherapy to treat brain metastasis.

PI_NAMEs: GOLOMB, SAMANTHA M (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Affect;anti-PD-L1 antibodies;Antibiotic Therapy;Antibiotics;Antibodies;Antitumor Response;Astrocytes;Biological Assay;Brain;brain behavior;Brain Neoplasms;brain remodeling;brain shape;brain tissue;cancer immunotherapy;cell type;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Central Nervous System;clinical application;combinatorial;Control Groups;Data;Development;differential expression;dysbiosis;effector T cell;Endothelial Cells;Environment;Etiology;fatty acid supplementation;Frequencies;Genetic Models;genetic signature;gut dysbiosis;gut microbiota;gut-brain axis;Histopathology;Immune;immune checkpoint blockade;Immune response;Immune signaling;Immune system;Immunity;Immunofluorescence Immunologic;Immunology procedure;Immunotherapy;improved;In Situ;in vivo;Incidence;Inflammatory;Inflammatory Response;insight;Light;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;Mediator;Melanoma;Metastasis Suppression;Metastatic malignant neoplasm to brain;microbiota;microbiota composition;Microglia;Molecular;mortality;mouse model;Mus;Myelogenous;Myeloid Cells;Neoplasm Metastasis;neoplastic cell;Neurons;neutrophil;novel;patient prognosis;Peripheral;Phenotype;Play;Prevention strategy;Process;Proto-Oncogene Protein c-kit;rational design;Regulation;response;Role;Shapes;Signal Transduction;Signaling Molecule;single cell analysis;Spatial Distribution;Stains;T cell differentiation;T-Cell Depletion;T-Cell Proliferation;T-Lymphocyte;Therapeutic;Transgenic Mice;Transplantation;treatment group;treatment strategy;tumor;tumor progression;Tumor Promotion;Volatile Fatty Acids

PROJECT_TITLE: Dissecting Gut Microbiota Modulation on Brain Metastasis Progression


ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: OVERALL NARRATIVE A serious complication of chronic lymphocytic leukemia (CLL) is the transformation from this relatively slow- growing malignancy to a highly aggressive lymphoma-like disease, called Richter's Syndrome (RS). Although the treatment landscape for patients with CLL has vastly improved over the last 5 years, the same therapeutic progress has been lacking for RS. Here, we aim to gain comprehensive understanding of the molecularly-defined subtypes of RS and its underlying cellular wiring so that we can more sensitively and accurately diagnosis it, and develop more rational therapeutic approaches to treat it; in this fashion, we propose a path by which individual patients with RS can be matched with specific tailored therapies.

PI_NAMEs: WU, CATHERINE JU-YING (contact)

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: accurate diagnosis;Address;Algorithms;anti-PD1 therapy;Apoptosis;Area;B-Lymphocytes;behavioral phenotyping;Biological;Biological Assay;Biology;Biometry;cancer cell;cell behavior;Cell Death;cell free DNA;Cell Physiology;Cell Therapy;Cells;chemotherapy;Chronic Care;Chronic Lymphocytic Leukemia;Clinical;clinical care;clinical investigation;Clustered Regularly Interspaced Short Palindromic Repeats;combinatorial;Combined Modality Therapy;Complication;Computer Analysis;curative treatments;Data;Data Set;design;Detection;Diagnosis;Diagnostic;diagnostic strategy;Disease;disease classification;Disease remission;disorder subtype;Dissection;DNA;effective therapy;Epigenetic Process;epigenomics;Evaluation;Exposure to;Funding;Gene Expression Profile;Genetic;Genome;genome editing;Genomics;Goals;Heterogeneity;human disease;Immuno-Chemotherapy;immunoregulation;Immunotherapeutic agent;improved;in vivo;Individual;individual patient;individualized medicine;interdisciplinary approach;International;Kinetics;Link;Lymphoma;Malignant Neoplasms;Maps;methylome;Modernization;Molecular;molecular subtypes;Monitor;morphological criteria;mouse model;multidisciplinary;Mus;next generation;Non-Invasive Detection;non-invasive monitor;novel;novel therapeutics;Outcome;Pathology;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern;personalized approach;Pharmaceutical Preparations;phase I trial;phenome;Phenotype;Prediction of Response to Therapy;Predisposition;programs;Proteins;Proteomics;rational design;Refractory;Research;Resistance;Resources;response;Richter's Syndrome;RNA;sample collection;Sampling;small molecule;small molecule libraries;Specimen;System;targeted agent;Therapeutic;therapy resistant;transcriptomics;treatment response;tumor;Vision

PROJECT_TITLE: Comprehensive dissection of the CLL genome & phenome to improve patient outcomes


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE The exact molecular mechanisms triggering RGC cell death and axonal degeneration in glaucoma are still not fully understood Poreover, the recent discovery that autophagy plays a yet unidentified role in the pathophysiology of glaucoma, and the conflicting evidence regarding its pro-survival or pro-cell death role suggest that the overall picture might be even more complex than anticipated. Therefore, it is imperative to gain a deeper understanding of the major pattern of RGC and axon loss and the crosstalk between autophagy and apoptosis in glaucoma. Identification of the early critical molecular events in RGCs in response to elevated IOP would add to our understanding of the nature of glaucomatous injury and provide potential targets for neuroprotective strategies for the treatment of glaucoma.

PI_NAMEs: LITON, PALOMA  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Acute;acute stress;Address;age-related disease;Agreement;Apoptosis;Apoptotic;Applications Grants;Autophagocytosis;Autophagosome;Axon;axon injury;axonal degeneration;Axonal Transport;Biological Models;Blindness;Cell Death;Cell Death Induction;Cessation of life;Chronic;Complex;Consensus;Data;Development;Disease;Early identification;Evaluation;Event;Exhibits;Experimental Models;Functional disorder;Genetic Models;Glaucoma;Homeostasis;human disease;hypertensive;Injury;Laboratories;Magnetism;Microspheres;Modeling;Molecular;Mus;Nature;Nerve Degeneration;neural;Neurodegenerative Disorders;neuron loss;Neuronal Injury;neuroprotection;new therapeutic target;novel;Ocular Hypertension;Optic Nerve;Organelles;overexpression;Pathogenicity;Pathway interactions;Pattern;pharmacologic;Physiologic Intraocular Pressure;Play;Process;Proteins;Regulation;response;response to injury;retinal ganglion cell degeneration;Retinal Ganglion Cells;Role;Scotoma;Signal Pathway;Stress;Testing;Therapeutic;Tissues;tool;Transgenic Mice;Transgenic Organisms;Traumatic injury;treatment strategy;Vesicle

PROJECT_TITLE: Autophagy and Retinal Ganglion Cell Death in Glaucoma

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Rare Diseases

PHR: Narrative: Richter’s Syndrome (RS) occurs when a patient’s Chronic Lymphocytic Leukemia (CLL) transforms to an aggressive, and often deadly, lymphoma. Unfortunately, when this occurs, there are very few therapeutic options with limited success, which is in part due to our lack of understanding of the biology underlying this disease and what triggers the transformation from an indolent leukemia into an aggressive lymphoma. In this Project, we will create a comprehensive atlas of the molecular features of RS and discover the changes that drive this transformation, and use this atlas to develop tools for assessing a patient’s risk, as well as a blood- based test for identifying and monitoring the emergence or recurrence of RS.

PI_NAMEs: GETZ, GAD A (contact)

PROJECT_TERMS: analytical method;anti-cancer research;Assessment tool;ATAC-seq;Atlases;Attention;B lymphoid malignancy;Biological Assay;Biological Markers;Biological Process;Biology;bisulfite sequencing;Blood;cell free DNA;Cell Physiology;Cells;Chromatin;Chromosome Mapping;Chronic Lymphocytic Leukemia;chronic lymphocytic leukemia cell;clinical decision-making;Clinical Trials;cohort;Collaborations;Collection;Data;data integration;Data Set;Detection;detection assay;Diagnostic;Disease;disorder control;Dissection;Early Diagnosis;Epigenetic Process;epigenome;Event;Evolution;exome;exome sequencing;Funding;Future;Genetic;Genetic study;Genome;genome analysis;genome sequencing;Genomics;Germ Lines;Goals;high risk;Histology;histone methylation;improved;Individual;Indolent;large cell Diffuse non-Hodgkin's lymphoma;leukemia;leukemic transformation;Lymphoma;Malignant Neoplasms;Manuscripts;Maps;Mass Spectrum Analysis;Molecular;molecular subtypes;Monitor;Mutate;Mutation;new therapeutic target;novel;Outcome;outcome prediction;Pathway interactions;Patient risk;Patient-Focused Outcomes;Patients;Pattern;phenome;phosphoproteomics;Plasma;predict clinical outcome;predicting response;prognostic model;Proteins;Proteomics;Recurrence;Refractory;Relapse;Resolution;Richter's Syndrome;risk stratification;Sampling;Signal Pathway;Signal Transduction;single cell analysis;single-cell RNA sequencing;success;targeted treatment;Testing;Therapeutic;therapeutic development;Therapeutic Intervention;therapeutic target;therapeutically effective;tool;transcriptome sequencing;transcriptomics;Venipunctures;whole genome;Work

PROJECT_TITLE: Generating an atlas of Richter's Syndrome: from molecular understanding to outcome prediction, detection and monitoring


ED_INST_TYPE: SCHOOLS OF OPTOMETRY/OPHT TECH

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Eye Disease and Disorders of Vision;Neurosciences;Physical Injury - Accidents and Adverse Effects;Wound Healing and Care

ORG_CITY: BIRMINGHAM

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The eye is 10 times more susceptible to exposure to vesicant chemical warfare agents than other organs, for example, the skin or the respiratory tract. The lack of molecular understanding of the underlying mechanism driving the ocular tissue pathobiology in victims of vesicant exposures impedes the development of effective medical countermeasures. In this proposal, we attempt to uncover the key molecular signaling controlling acute and chronic stages of ocular injury in animals with direct ocular exposure to vesicants.

PI_NAMEs: GORBATYUK, MARINA  (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Ablation;Acute;Affect;Agreement;Animal Model;Animals;Antidotes;Apoptotic;Automobile Driving;Blindness;Blood Vessels;Bulla;Cell Death;central retinal vein occlusion;Cessation of life;Chemical Warfare Agents;Chronic;combat;Cornea;corneal epithelium;Corneal Injury;Corneal Neovascularization;Corneal Opacity;Cultured Cells;Data;Development;Dose;Electroretinography;Endothelial Cells;Epithelial Cells;experience;experimental study;Exposure to;Extravasation;Eye;Eye Injuries;Functional disorder;Future;Genetic;Goals;Harvest;healing;Homologous Gene;Human;Individual;Inflammation;Injury;Iran;Iraq;lewisite;Link;Mechlorethamine;Mediating;Mediator;medical countermeasure;Molecular;Mus;Mustard Gas;neovascularization;novel;Organ;overexpression;Oxides;Pathogenesis;Penetration;Photophobia;Photoreceptors;Population;Predisposition;prevent;Proteins;Publishing;Reporting;Respiratory System;response;Retina;retina blood vessel structure;retinal toxicity;Retrospective Studies;Severities;Signal Transduction;Skin;small molecule inhibitor;Survivors;Symptoms;Time;tissue injury;Tissues;tool;toxicant;transmission process;Tupaiidae;Up-Regulation;Vascular Endothelial Growth Factors;vascular injury;Vascularization;Vegf Inhibitor;VEGF Trap;Vesicants;Vision;War

PROJECT_TITLE: The mechanism of vesicant-induced ocular injury


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Racial and ethnic minorities represent the fastest growing segment of the United States adult population, yet they remain significantly underrepresented in cancer clinical trials (CCTs). The overarching goal of this proposal is to create an evidence-based, scalable communication strategy to increase referrals to CCTs in Florida by clinicians, community health educators (CHEs), and patients through engagement with the ALEX Research Portal. The Portal will consolidate referral channels, extend the reach of CHEs, and facilitate access to culturally and linguistically tailored resources.

PI_NAMEs: CARRASQUILLO, OLVEEN ;RAUP-KRIEGER, JANICE LEE (contact)

PROGRAM_OFFICER_NAME: SAN MIGUEL-MAJORS, SANDRA L

PROJECT_TERMS: Address;Adult;Black race;Cancer Center;cancer clinical trial;Cancer health equity;Cancer Patient;Caregivers;Clinic;Clinical Research;clinical trial recruitment;Clinical Trials;Collaborations;Communication;Communities;Community Health;Complex;Conduct Clinical Trials;cost;Custom;Data;data repository;digital;Dissemination and Implementation;Early Therapeutic-Clinical Trials Network;Enrollment;ethnic diversity;ethnic minority;evidence base;Evidence based intervention;experience;Family;Family member;Florida;Funding;Geographic Locations;Geography;Goals;Health Educators;Hispanic;Human;improved;Inequity;Interactive Systems Framework;Intervention;Knowledge;Language;Latino;Life;Linguistics;Malignant Neoplasms;member;Minority Enrollment;Minority Groups;minority patient;Modeling;Morbidity - disease rate;mortality;older adult;online community;Outcome;Participant;Pathway interactions;patient navigation;patient portal;patient registry;Patients;Phase;Population;Population Heterogeneity;preference;primary outcome;Process;racial diversity;racial minority;Randomized;Randomized Controlled Clinical Trials;Recording of previous events;recruit;Research;Resources;Role;Schedule;Science;Screening for cancer;secondary outcome;social media;Source;Techniques;Technology;Testing;Translating;Trust;Underrepresented Populations;United States;Universities;user centered design;videoconference;virtual human;Visit;web site;Work

PROJECT_TITLE: Precision Clinical Trial Recruitment to Promote Cancer Health Equity Across Florida


ORG_CITY: LOS ANGELES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE This Type 2 R35 proposal builds on the science from the current OIA. We propose to use state-of-the-art approaches to analyze large numbers of patient biopsies, use CRISPR screens for mechanistic analyses and use model systems to improve responses and treat resistance to cancer immunotherapies.

PI_NAMEs: RIBAS, ANTONI  (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Adoptive Cell Transfers;anti-tumor immune response;Antigen Presentation;Antigens;Antitumor Response;Area;Back;Bioinformatics;Biological Models;Biopsy;BRAF gene;cancer cell;cancer immunotherapy;Cell Line;Cell Physiology;Clinical;Clinical Trials;combinatorial;Combined Modality Therapy;CRISPR screen;cytokine;data modeling;Drug Screening;Engineered Gene;Exposure to;Functional disorder;Funding;Genes;Genetic;immune checkpoint blockade;Immunotherapy;improved;in vivo;Interferon Type II;Knock-out;Knowledge;loss of function mutation;MEKs;Melanoma;Melanoma Cell;Methods;mouse model;next generation;novel therapeutics;Pathway Analysis;Patients;PD-1 inhibitors;pharmacologic;programmed cell death ligand 1;programs;repository;Resistance;response;Science;Shapes;Signal Pathway;T cell therapy;T-Cell Receptor;T-Lymphocyte;targeted treatment;Testing;transcription factor;tumor

PROJECT_TITLE: Next Generation Cancer Immunotherapies to Defeat Melanoma


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: SYRACUSE

ORG_NAME: SYRACUSE VA  MEDICAL CENTER

PHR: Many Veterans experience psychological distress that is further complicated by unmet social needs (e.g., housing/food instability) and seek care from VHA’s integrated Patient Aligned Care Teams (PACTs) in primary care. Although the VHA has integrated PACTs with additional resources by adding specific providers with specialized skillsets, such as social workers and Primary Care-Mental Health Integration providers, there is significant variability among integrated PACTs in Veterans’ access to care. This proposal builds upon this prior work and seeks to evaluate integrated PACT characteristics and their relationship with access within this Veteran population with complex needs. A noted gap in the literature, we aim to identify integrated PACT characteristics and processes that can be used to further optimize care for these complex Veterans. Another novel aspect of this research is its utilization of multiple sources of data to partner results obtained from the electronic medical record with surveys from PACT members’ and Veteran perspectives.

PI_NAMEs: FUNDERBURK, JENNIFER S (contact)

PROJECT_TERMS: Address;Administrator;Affect;Area;Attention;Behavior;burnout;Care given by nurses;care seeking;care systems;Caring;Case Manager;Characteristics;Clinical Nursing;comorbidity;Competence;Complex;Computerized Medical Record;Data;Data Sources;design;Dimensions;electronic data;Eligibility Determination;Equation;Evidence based intervention;experience;Food;food insecurity;Future;Health;Health Services Accessibility;Healthcare;Homelessness;Housing;housing instability;Improve Access;improved;innovation;Intervention;Interview;Literature;Measures;Mediating;Mediator;Medical;meetings;member;Mental Health;Mental Health Services;Methodology;Methods;military veteran;Modeling;Monitor;multidisciplinary;multiple data sources;novel;Nurses;patient navigation;Patient-Focused Outcomes;Patients;Perception;Play;Population;Primary Care;primary care patient;primary care provider;primary care setting;Process;Provider;psychologic;psychological distress;psychosocial;Publications;Quality of Care;Quality of life;Recommendation;Reporting;Research;Resources;Risk;Role;Sampling;skills;social;social health determinants;Social Work;Social Workers;Structure;success;Surveys;Testing;Time;Training;Variant;Veterans;Visit;Work

PROJECT_TITLE: Identifying Modifiable Factors that Affect Veterans At-Risk due to Social Determinants of Health and Psychological Distress Access to Care Within Integrated Primary Care Settings

STUDY_SECTION_NAME: Social Determinants of Health[HS2A]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Immunotherapy;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Rare Diseases

PHR: Narrative A serious complication of chronic lymphocytic leukemia (CLL) is the transformation from this relatively slow- growing malignancy to a highly aggressive lymphoma-like disease, called Richter's Syndrome (RS). Since newer therapies for RS are beginning to show promise in the treatment of this deadly entity, we propose to perform a parallel analysis of evolution of both RS cells and their surrounding immune cells over time and in relationship to these novel therapeutic strategies. By employing a suite of cutting-edge experimental tools, new analytic pipelines and new animal models, we will perform an in-depth tumor cell and immune profile analyses of samples collected from a unique portfolio of innovative investigator-initiated clinical trials for which clinical response data will be linked; and we will investigate the idea that tumor cells shape and are shaped by their immune microenvironment.

PROJECT_TERMS: Address;Allogenic;American Society of Clinical Oncology;analytical tool;Animal Model;Antigens;BCL2 gene;biomarker identification;Cell Shape;Cells;Cessation of life;Characteristics;chemotherapy;Chronic Lymphocytic Leukemia;Clinical;clinical investigation;Clinical Investigator;Clinical Trials;Combined Modality Therapy;Complication;CRISPR/Cas technology;curative treatments;Data;Detection;Development;Disease;Disease remission;disorder control;Dissection;DNA sequencing;Engineering;Enrollment;Evolution;exome sequencing;experience;Flow Cytometry;Funding;Genetic;Genetically Engineered Mouse;Genome;Genomics;Hematopoietic Stem Cell Transplantation;human disease;Immune;immune cell infiltrate;immune checkpoint blockade;Immunity;Immunogenomics;Immunohistochemistry;improved;in vivo;Incidence;Individual;Infiltration;inhibitor;innovation;insight;Link;longitudinal analysis;loss of function;lymph nodes;Lymphoma;Malignant Neoplasms;Marrow;Mediating;Modeling;Molecular;Mus;Mutation;neoplastic cell;novel;novel therapeutic intervention;novel therapeutics;Outcome;Pathway interactions;patient response;Patient-Focused Outcomes;Patients;phenome;Phenotype;Population;predicting response;programmed cell death protein 1;Proteins;Regimen;Research Personnel;Resistance;responders and non-responders;response;Richter's Syndrome;Role;Sampling;Shapes;single-cell RNA sequencing;Specificity;Specimen;Statistical Data Interpretation;T cell infiltration;T-cell receptor repertoire;T-Lymphocyte;Therapeutic;Therapeutic Agents;therapeutic development;Therapeutic Trials;therapy resistant;Time;Tissue Microarray;Tissues;tool;TP53 gene;transcriptome;transcriptome sequencing;treatment response;tumor;tumor-immune system interactions;Validation

PROJECT_TITLE: Defining the determinants of response and resistance to therapy for Richter's Syndrome


NIH_SPENDING_CATS: Lymphatic Research

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative Lymphatic disorders, which affect upwards of 200 million people worldwide, are not well characterized and lack any pharmacological treatment. Defining and understanding the process of lymphangiogenesis will facilitate treatment of lymphatic disorders and improve patient outcome. This training proposal aims to molecularly characterize the Adrenomedullin-RAMP3-ACKR3 signaling axis and clarify its role in the process of healthy and pathological lymphangiogenesis.

PI_NAMEs: SERAFIN, DONALD STEPHEN (contact)

PROJECT_TERMS: adrenomedullin;adrenomedullin receptor;Affect;Binding;Biological Assay;Biology;Biotin;Blood Vessels;C-terminal;Cell membrane;cell motility;Cell Proliferation;Cells;chemokine receptor;Chronic Disease;Clinical Management;Co-Immunoprecipitations;Communication;Defect;Development;Diameter;Dimerization;Embryo;Ethics;experience;FDA approved;Functional disorder;G-Protein-Coupled Receptors;Genetic;Growth;Harvest;Human;Immunohistochemistry;Impairment;improved;In Vitro;in vivo;innovation;Intercellular Fluid;interest;knock-down;Knowledge;Laboratories;Laboratory Study;Ligands;Lymphangiogenesis;Lymphatic;Lymphatic Diseases;Lymphatic Endothelial Cells;Lymphatic Endothelium;lymphatic vessel;Mass Spectrum Analysis;Mediating;migration;Modeling;Molecular;Molecular Biology;mouse model;Mus;N-ethylmaleimide-sensitive protein;novel;Output;overexpression;Pain;Pathologic;Patient-Focused Outcomes;Peptides;Performance;Persons;Pharmacological Treatment;prevent;Process;Proliferating;protein protein interaction;Proteins;Publishing;receptor;receptor function;receptor internalization;receptor-activity-modifying protein;Recycling;Regulation;Reporter;Reporting;Research;Retina;Role;Signal Pathway;Signal Transduction;Techniques;Therapeutic;trafficking;Training;Western Blotting

PROJECT_TITLE: Elucidating the GPCR protein networks that drive lymphatic growth


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Sexual and gender minority adults bear an excess burden of harmful alcohol use (e.g., binge drinking and hazardous alcohol use), necessitating exploration of underlying causal mechanisms. Structural drivers of harmful alcohol use disparities in the form of state equality-promoting policies are underexplored yet offer an important opportunity for applying advanced econometrics methods to rigorously estimate causal effects. This study proposes a triple differences approach with causal identifiability assumptions to examine potential differential effects of state equality-promoting policies on binge drinking and hazardous alcohol use for U.S. sexual and gender minority adults compared to cisgender straight adults from 2014-2022.

PI_NAMEs: TURNER, CAITLIN MARIE (contact)

PROGRAM_OFFICER_NAME: PARASURAMAN, SARIKA RANE

PROJECT_TERMS: Address;Adult;Alcohol abuse;alcohol consequences;Alcohol consumption;Alcohol dependence;alcohol research;Alcohols;Behavioral Risk Factor Surveillance System;binge drinking;Birth;career;cisgender;Data;Disparity;disparity reduction;econometrics;Educational Status;Employment;Environment;evidence base;Gender;gender minority;gender minority group;gender minority health;gender minority health disparity;Gender Role;General Population;Goals;hate crimes;Housing;indexing;Individual Differences;Intervention;Laws;Lesbian Gay Bisexual;Libido;Link;Literature;Measures;men;Mentorship;Methods;minority disparity;minority stress;Modeling;Morbidity - disease rate;mortality;Names;National Institute on Alcohol Abuse and Alcoholism;Policies;Population;public policy on alcohol;Research;Research Personnel;Services;sex assigned;Sex Orientation;Sexual and Gender Minorities;sexual minority;sexual minority disparity;sexual minority group;sexual minority men;sexual minority women;skills;social determinants;Social Policies;social stigma;Specific qualifier value;Strategic Planning;training opportunity;transgender men;transgender women;Variant;Woman;women versus men

PROJECT_TITLE: Examining differential effects of state equality-promoting policies on harmful alcohol use among sexual and gender minority adults in the U.S.: an econometrics approach for causal inference


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

PHR: PROJECT NARRATIVE Type 2 diabetes-associated breast cancer supports an immunosuppressive microenvironment that impairs CD8+ T cell anti-tumor response and promotes regulatory T cell immunosuppression via dysregulated Hedgehog signaling, precipitating into poorer overall and disease-free outcomes in this distinct, but highly prevalent, patient subset. More studies are required in understanding the modulation of CD8+ and regulatory T cell activity by Hedgehog signaling and hyperglycemia during mammary tumorigenesis. This proposal will elucidate the roles of hyperglycemia and Hedgehog signaling in breast cancer progression and control, as well as support the initiative of developing effective combination therapies for highly-aggressive, diabetes- associated breast cancer.

PI_NAMEs: SWAIN, COURTNEY A (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Antigens;Antitumor Response;Applications Grants;Automobile Driving;Bioenergetics;Bioinformatics;Biological Assay;Biological Models;Breast Cancer Patient;breast cancer progression;Breast Cancer therapy;Breast Cancer Treatment;Breast Carcinoma;Cancer Control;cancer infiltrating T cells;career;CD8-Positive T-Lymphocytes;CD8B1 gene;Clinical;Combined Modality Therapy;Competence;cytokine;cytotoxic;Data;Diabetes Mellitus;diabetic;diabetic patient;Disease;Doctor of Philosophy;Environment;Erinaceidae;exhaustion;Female;Foundations;FOXP3 gene;Functional disorder;Genes;Genetically Engineered Mouse;Glucose Intolerance;glycemic control;Glycolysis;Goals;Hyperglycemia;Immune;immunogenicity;Immunologics;Immunosuppression;Immunotherapy;Impairment;Infiltration;Investigation;Lymphocyte;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Neoplasms;Mammary Tumorigenesis;marginalized population;Mentors;Mentorship;Metabolic;Metabolism;Metformin;Modeling;Morbidity - disease rate;mouse model;Nomenclature;Non-Insulin-Dependent Diabetes Mellitus;novel;Oncologist;Outcome;Pathogenesis;patient population;patient subsets;Patients;Peripheral;Phenotype;Physicians;Population;pre-clinical;Pre-Clinical Model;Primary Neoplasm;Process;Production;Prognosis;programs;Readiness;Regulatory T-Lymphocyte;Reporting;Reproducibility;Research;Research Project Grants;response;responsible research conduct;Risk;Role;Scientist;Signal Pathway;Signal Transduction;smoothened signaling pathway;Solid;stem;T-Lymphocyte;T-Lymphocyte Subsets;Techniques;Training;treatment and outcome;treatment response;triple-negative invasive breast carcinoma;tumor;tumor microenvironment;tumor-immune system interactions;tumorigenic;Type 2 diabetic;United States;Woman;Work

PROJECT_TITLE: Investigating the impact of hyperglycemia on modulating T cell populations in breast cancer


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Lymphatic Research;Women's Health Research

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative Current immunotherapeutic approaches largely fail to improve survival for patients with breast cancer, the second-leading cause of cancer related deaths of women in the United States. Completion of this research proposal will advance our understanding of how loss of tumor-intrinsic REST function, found in 15-20% of breast cancers, promotes an immune suppressive tumor microenvironment, which may, in part, promote resistance to immunotherapy. Information gained from these studies will provide targetable mechanisms to increase sensitivity to immunotherapies in REST-less breast cancer with the potential to inform treatment strategy for other REST- less tumor types.

PI_NAMEs: MICHAUD, DANIEL E (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Agitation;anti-PD-1;Antigens;Biological Assay;biomarker discovery;biomarker identification;Breast Cancer Cell;cancer cell;Cancer Etiology;career;CD8-Positive T-Lymphocytes;Cell secretion;Cells;Cellular Immunity;Characteristics;chemokine;Coculture Techniques;CSF1R gene;cytokine;Cytometry;cytotoxicity;Data;effector T cell;Flow Cytometry;functional loss;Gene Expression Profile;Genes;Goals;Grant;Immune;immune cell infiltrate;immune checkpoint blockade;Immune response;Immunofluorescence Immunologic;Immunologist;immunoregulation;Immunosuppression;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;in vivo Model;Infiltration;Intrinsic factor;KDR gene;Knock-out;Link;loss of function;Lymphangiogenesis;Lymphatic;Lymphatic Endothelium;Lymphocyte;Lymphocyte Activation;Lymphocyte Function;Lymphocyte Suppression;Lymphocytic Infiltrate;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Mediating;Migration Assay;Modeling;molecular subtypes;Mus;Myelogenous;nano-string;Neurosecretory Systems;novel;Outcome;Pathway Analysis;Patients;Periodicity;Phenotype;Population;Positioning Attribute;Prognosis;prognostic of survival;programmed cell death ligand 1;Proliferating;recruit;Refractory;Regulation;Research;Research Proposals;Resistance;response;Rest;RNA;RNA analysis;Role;Signal Transduction;single-cell RNA sequencing;skills;Solid Neoplasm;synergism;T-Lymphocyte;targeted treatment;Technical Expertise;Testing;The Cancer Genome Atlas;Therapeutic;Training;Transcription Repressor;transcriptome;transcriptome sequencing;treatment response;treatment strategy;tumor;tumor growth;tumor microenvironment;Tumor Promotion;Tumor-associated macrophages;tumor-immune system interactions;Tumor-Infiltrating Lymphocytes;United States;Vascular Endothelial Growth Factors;Women's mortality;Writing

PROJECT_TITLE: Mechanisms of REST-mediated immunosuppression in cancer


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Eye Disease and Disorders of Vision;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Wound Healing and Care

ORG_CITY: Columbus

ORG_DEPT: SURGERY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Chemical vesicant exposure poses a potential threat to our society. Currently, there are no effective countermeasures to treat vesicant-induced corneal injury. This U01 aims to develop a novel protein therapeutic that can be stockpiled and conveniently deployed to mitigate vesicant induced damages to the eye.

PI_NAMEs: CHANDLER, HEATHER  (contact);MA, JIANJIE ;ZHU, HUA

PROJECT_TERMS: Ablation;Acute;Advanced Development;Affect;Animal Model;Aqueous Humor;Benefits and Risks;Biology;Cell membrane;Cellular Structures;chemical threat;Chemicals;Contracts;Cornea;corneal epithelial stem cells;corneal epithelial wound healing;corneal epithelium;Corneal Injury;Cutaneous;Data;Dermal;Development;Dose;Environment;Epithelial Cells;epithelium regeneration;Event;extracellular;Eye;Eye Injuries;Eyedrops;Fibrosis;Film;First Aid;Goals;Goblet Cells;Homeostasis;Human;Immune response;improved;In Vitro;in vivo;Infiltration;Injury;irritation;Joints;Knowledge;Lesion;limbal;live cell imaging;Manuscripts;Measures;Mechlorethamine;Medical;Medicine;member;Modeling;Mus;Mustard Gas;Nature;novel;Ocular Pathology;ocular surface;Ohio;Organ;Oryctolagus cuniculus;Patients;Pharmacologic Substance;Phase;Photophobia;Physiology;preservation;Process;Production;Program Development;programs;Protein Family;Proteins;Protocols documentation;Publishing;pulmonary symptom;re-epithelialization;Reagent;Recombinants;Regenerative capacity;Regenerative Medicine;Regimen;repaired;Resistance;Respiratory System;response to injury;Rodent;Role;Safety;screening program;Societies;stem cell function;stem cell survival;stem cells;Stress;Surface;Symptoms;Technology;Therapeutic;therapeutic protein;tissue injury;tissue repair;Topical application;Toxic effect;Toxicology;Transgenic Mice;Treatment Efficacy;TRIM Gene;Ulcer;United States National Institutes of Health;Universities;validation studies;Vascularization;Vesicants;Wild Type Mouse;wound healing

PROJECT_TITLE: First Aid Medicine to Treat Vesicant Induced Corneal Injury

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-P(50)]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Obesity;Prevention;Women's Health Research

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: PROJECT NARRATIVE Breast cancer is the most common cancer in the United States and its incidence and mortality increase with obesity. This proposal aims to investigate if hypertrophic expansion of mammary adipocytes upon weight gain contributes to the poor prognosis of obese breast cancer patients via vesicle-mediated alterations to tumor cell metabolism. Collectively, this proposal will identify molecular mechanisms between adipocytes and tumor cells that can be targeted in the clinic and indicate if mammary adipocyte hypertrophy could serve as a prognostic biomarker for breast cancer patients.

PI_NAMEs: BEEGHLY, GARRETT F (contact)

PROJECT_TERMS: Actins;Address;Adipocytes;Adipose tissue;Adopted;Adult women;behavior in vitro;Biogenesis;Biological Assay;Biological Markers;Biophysics;Biopsy;Body mass index;Breast;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Patient;breast cancer progression;Breast Cancer Risk Factor;Cancer Prognosis;cell behavior;cell motility;Cell Proliferation;Cell Separation;cell type;Cells;Chemoresistance;Clinic;Clinical;Coculture Techniques;cohort;Communication;Cues;Cytoskeleton;Data;Data Analyses;Diameter;Exhibits;Experimental Designs;experimental study;extracellular vesicles;fatty acid oxidation;Frequencies;Genes;genetic inhibitor;Goals;humane endpoint;Hypertrophy;imaging study;implantation;improved;In Vitro;in vivo;Incidence;Inguinal lymph node group;Injections;Institution;interest;Intervention;Invaded;Lipids;Malignant Breast Neoplasm;Malignant Neoplasms;Mammaplasty;mammary;Mammary Duct;Mass Spectrum Analysis;Mediating;Mediator;Mentors;Mentorship;Metabolic Diseases;Metabolic dysfunction;Methods;Microfluidics;MicroRNAs;migration;Molecular;mortality;Mus;nanoparticle;neoplastic cell;Obese Mice;obese person;Obesity;Obesity Epidemic;Organ;Organoids;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;precursor cell;Prognosis;Prognostic Marker;Proliferating;Research;Research Personnel;Risk Factors;Science;skills;Smoking;Sorting;targeted treatment;Techniques;Thinness;Tissues;Training;Transcriptional Regulation;transcriptome sequencing;tumor;tumor metabolism;tumor progression;Tumor Promotion;United States;Vesicle;vesicular release;Weight;Weight Gain;Woman;Work

PROJECT_TITLE: Hypertrophic adipocytes as biophysical mediators of breast cancer progression


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Neurosciences

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative During development, seven distinct and essential retinal cell types are formed. The formation of three of these cell types relies upon Otx2, yet how this transcription factor's expression is regulated during retinal development is poorly understood. Here, I will determine how multiple enhancers combine to regulate Otx2 expression and how they can substitute for each other during development.

PI_NAMEs: PURVIS, IAN J (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Ablation;Adopted;Adult;Amacrine Cells;Animals;Biological Assay;Bite;Brain;career;cell type;Cells;chromosome conformation capture;Clustered Regularly Interspaced Short Palindromic Repeats;Compensation;Complex;CRISPR interference;CRISPR/Cas technology;Development;DNA;DNA Sequence;Electroporation;Embryo;Enhancers;Ensure;experience;experimental study;Frequencies;Gene Expression;Gene Silencing;Genes;homeodomain;horizontal cell;improved;Interneurons;Knowledge;Light;Liver;loss of function;Mediating;Modeling;Mus;novel;Occupations;Pattern;Phenotype;Photoreceptors;Plasmids;Play;postmitotic;postnatal;precursor cell;prevent;Production;promoter;Regulation;Resolution;Retina;Retinal Cone;retinal rods;Role;Techniques;Testing;Tissues;transcription factor;Untranslated RNA;Vertebrate Photoreceptors;Vision;visual information

PROJECT_TITLE: In The Loop: Investigating Enhancer-Mediated Regulation of OTX2 During Retinal Development

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-D(21)L]


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

ORG_CITY: KANSAS CITY

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE Greater than 90% of Pancreatic Ductal Adenocarcinoma (PDAC) cases harbor a mutation in KRAS that allows continuous, sustained activity. We’ve found that SHP2 is essential for PDAC development by playing a role in promoting KRAS signaling, but we’ve found it functions in other signaling pathways that can drive tumor progression, as well. Therefore, we propose that SHP2 acts in multiple ways to promote tumor growth, providing tumors resistance to treatments that block KRAS signaling alone.

PI_NAMEs: WALSH, RICHARD MCKINNON (contact)

PROGRAM_OFFICER_NAME: SCHMIDT, MICHAEL K

PROJECT_TERMS: Ablation;Address;Affect;Aggressive behavior;Binding;Bioenergetics;Calcium;calcium metabolism;Calcium Signaling;cancer cell;Cancer Etiology;Catabolism;Cell Line;Cell Survival;cell type;Cells;Cessation of life;Citric Acid Cycle;Consumption;Data;Data Analyses;Dependence;design;Development;Disabling;Disease;Disease Progression;Endoplasmic Reticulum;enzyme activity;Enzymes;extracellular;Genetic;genome-wide;Genus Hippocampus;Global Change;Glycolysis;Goals;Impairment;improved;improved outcome;In Vitro;Individual;inhibitor;insight;interest;Ions;Knock-out;KRAS2 gene;liquid chromatography mass spectrometry;Literature;MAP Kinase Gene;mass spectrometer;Mediating;MEK inhibition;MEKs;Metabolic;Metabolic stress;Metabolism;Methods;migration;Mitochondria;mitochondrial membrane;Modeling;Molecular;mouse model;Mus;mutant;Mutate;Mutation;Nodal;novel;Oncogenes;Oncogenic;Outcome;Oxidoreductase;pancreas development;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;Pathway Analysis;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;phosphoproteomics;PLC gamma1;Positioning Attribute;prevent;Process;Production;Proliferating;Proteins;Proteome;PTPN11 gene;Regulation;release of sequestered calcium ion into cytoplasm;Resistance;resistance mechanism;response;Role;Sampling;Signal Pathway;Signal Transduction;Source;Stress Tests;System;targeted treatment;Testing;therapeutic development;Tissues;Traction;tumor;tumor growth;tumor progression;Tumor Promotion;tumorigenic;Tumorigenicity;vector;Veins

PROJECT_TITLE: Investigating the role of SHP2-PLCG1 interaction in PDAC calcium signaling and metabolism


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative Many undruggable targets are involved in intracellular protein-protein interactions (PPIs), which are challenging to inhibit with small molecules and antibodies. Cell-penetrating miniproteins are a promising class of proteins which have the potential to inhibit various PPIs in disease. The proposed research aims to identify the determinants of cytosolic delivery in a multiplexed approach to understand and develop new cell-penetrating miniproteins.

PI_NAMEs: PHOUMYVONG, CLAIRE M (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Antibodies;Binding;Biological Products;Cell membrane;Cells;cellular targeting;Charge;Complex;covalent bond;Cytosol;design;Diffuse;Disease;Endosomes;Enzymes;extracellular;FDA approved;Gel;Goals;Human;human disease;Hydrophobicity;Incubated;Individual;inhibitor;Libraries;Mass Spectrum Analysis;Measures;Methods;novel drug class;novel strategies;Penetration;peptide drug;Peptide Hydrolases;Peptides;Pharmaceutical Preparations;Plasma Cells;Property;Protein Engineering;Protein Inhibition;protein protein interaction;Proteins;Publishing;Reaction;Recovery;Research;Sampling;small molecule;Specificity;Structure;success;Surface;System;Tertiary Protein Structure;Testing;Therapeutic;therapeutic protein;Visualization;Work

PROJECT_TITLE: Identifying the determinants of cell-penetrant miniproteins


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative The overall goal of the T32-supported Visual Sciences Training Program (VSTP) is to recruit talented young researchers, both pre- and postdoctoral fellows, and provide them with broad research training in the visual system, ranging from normal development and function to mechanisms of vision loss in the context of human disease. This training will prepare the trainees for careers in the visual sciences.

PI_NAMEs: NATHANS, JEREMY ;RIAZUDDIN, AMER ;ZACK, DONALD J. (contact)

PROJECT_TERMS: Training Programs;vision science

PROJECT_TITLE: Visual Science Training Program


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Neurodegenerative;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: NARRATIVE Autosomal dominant optic atrophy (DOA) is the most commonly diagnosed inherited optic neuropathy, and a disease for which there is no treatment. We will use CRISPR/Cas9 based genome editing techniques and human pluripotent stem cells to generate three new DOA models that track DOA disease progression from stem cell differentiation to retinal ganglion cell (RGC) degeneration. We propose to use these models to study the role of OPA1 in RGC differentiation and degeneration.

PI_NAMEs: ZACK, DONALD J. (contact)

PROGRAM_OFFICER_NAME: HENLE, STEVEN JOHN

PROJECT_TERMS: Action Potentials;ATOH7 gene;Autosomal Dominant Optic Atrophy;Biochemical;Biological Models;Cell Death;Cell Death Induction;Cell Differentiation process;cell injury;Cell model;Cell Survival;Cells;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Comparative Study;Competence;CRISPR/Cas technology;Cytoprotection;Defect;Development;Diagnosis;differentiation in vitro;Disease;disease mechanisms study;Disease Progression;drug discovery;Dynamin;Energy Metabolism;Exhibits;experimental study;Eye;Eye diseases;Family;functional genomics;Future;Ganglion Cell Layer;Gene Dosage;Genes;Genetic Transcription;genome editing;Guanosine Triphosphate Phosphohydrolases;high throughput screening;Homeostasis;Human;human embryonic stem cell;human induced pluripotent stem cells;human pluripotent stem cell;human stem cells;in vivo;induced pluripotent stem cell;Induction of Apoptosis;Inherited;inhibitor;Lead;loss of function;Methods;Mitochondria;mitochondrial dysfunction;Modeling;Morphology;mouse model;Mus;mutant;Mutation;Neurons;Neuroprotective Agents;OPA1 gene;Optic Disk;optic nerve disorder;Oxidative Phosphorylation;Oxidative Stress;Oxidative Stress Induction;Pathogenesis;patient derived induced pluripotent stem cells;Patients;Pilot Projects;Population;Predisposition;Process;programs;protective pathway;Proteins;Protocols documentation;Reactive Oxygen Species;regenerative agent;resilience;Retina;retinal ganglion cell degeneration;Retinal Ganglion Cells;retinal nerve fiber layer;Role;Sales;Sampling;Secondary to;single-cell RNA sequencing;Site;SOX11 gene;Specific qualifier value;stem cell differentiation;stem cell model;stem cells;Study models;System;Techniques;tert-Butylhydroperoxide;Testing;Thinness;transcription factor;transcriptomics;Undifferentiated

PROJECT_TITLE: Role of OPA1 in Retinal Ganglion Cell Differentiation and the Pathogenesis of Dominant Optic Atrophy

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


ORG_CITY: DETROIT

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: Project Narrative Bone metastasis results in significant morbidity and mortality for prostate cancer patients due to the supportive roles of the bone marrow microenvironment in promoting tumor aggressiveness. The proposed research will investigate how the interaction between tumor cells and fat cells within the bone marrow activates adaptive mechanisms to promote PCa survival and progression in bone. This study will elucidate novel interactions between bone marrow adipocytes and PCa cells that affect tumor cell metabolism and potentially reveal novel therapeutic targets for treating this presently incurable disease.

PI_NAMEs: WILSON, ALEXIS RYLEE (contact)

PROJECT_TERMS: Address;Adipocytes;Adipose tissue;Affect;Age;Amino Acids;arm;Aspartate-Ammonia Ligase;biological adaptation to stress;bone;Bone Marrow;Cancer Patient;cancer survival;cancer type;Cell Communication;Cell Culture Techniques;Cell Death;Cell Energetics;cell growth;Cell Line;Cell model;Cell Survival;cell type;Cells;Cessation of life;Chemoresistance;chemotherapy;Coculture Techniques;Data;Defense Mechanisms;Detection;Disease;docetaxel;Endoplasmic Reticulum;endoplasmic reticulum stress;Enzymes;Exposure to;Future;Genes;Glutamine;Growth;Homeostasis;Human;improved;In Vitro;in vivo;in vivo Model;Incidence;Inflammatory;knock-down;Link;Lipase;Lipid Mobilization;Lipid Peroxidation;Lipids;Lipolysis;Malignant neoplasm of prostate;Marrow;Mediating;Metabolic;Metabolism;metabolome;metabolomics;Metastatic Neoplasm to the Bone;Metastatic Prostate Cancer;Modeling;Molecular;Molecular Target;Morbidity - disease rate;mortality;mouse model;Mus;neoplastic cell;new therapeutic target;novel;Obesity;Oxidative Stress;palliative;Pathway interactions;pharmacologic;Phenotype;Play;Prevention;prostate cancer cell;prostate cancer metastasis;Research;response;Role;Signal Transduction;Site;skeletal disorder;Stearoyl-CoA Desaturase;stem;Stress;Testing;transcriptome sequencing;tumor;tumor growth;tumor metabolism;tumor progression;Tumor Promotion;Work

PROJECT_TITLE: ATF4-SCD axis in bone metastatic prostate cancer


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

PHR: Narrative Richter's Syndrome (RS) is the appearance of an aggressive, difficult-to-treat lymphoma from a prior case of chronic lymphocytic leukemia. We have developed a novel method, called BH3 profiling, for identifying drugs that coax cancer cells into destroying themselves. Here we propose to employ BH3 profiling on samples from patients with RS to expand the therapeutic options for RS.

PI_NAMEs: LETAI, ANTHONY G (contact)

PROJECT_TERMS: Address;Apoptosis;Apoptotic;Appearance;Back;BCL1 Oncogene;BCL2L1 gene;BH3 peptide;Biological;Biological Assay;Biological Models;cancer cell;Cell Death;Cell Physiology;Cells;Cessation of life;Chronic Lymphocytic Leukemia;Clinical;clinical predictors;Clinical Trials;Collaborations;companion diagnostics;Coupled;Data;Dependence;Dissection;Drug Exposure;Drug Screening;drug sensitivity;Drug Targeting;early phase clinical trial;effective therapy;Ensure;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Family;Funding;Genome;Genomic approach;Genomics;Goals;Human;improved;in vivo;Individual;Induction of Apoptosis;inhibitor;insight;Intervention;Learning;Liquid substance;Lymphoma;Malignant neoplasm of lung;Maps;MCL1 gene;Measures;Medical;Methods;mimetics;Mitochondria;Modeling;Molecular Abnormality;mouse model;mutant;novel;Occupations;Pathology;Patient-Focused Outcomes;Patients;Pattern;Permeability;Pharmaceutical Preparations;pharmacologic;phenome;precision medicine;predicting response;Proteins;Proteomics;Regulation;Resistance;response;Richter's Syndrome;Sampling;Signal Pathway;Signal Transduction;small molecule;Solid Neoplasm;Specimen;success;Techniques;Testing;Therapeutic;transcriptomics;translational applications;tumor

PROJECT_TITLE: Functional identification of drug response and resistance in Richter's Syndrome


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

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE The proposed studies focus on understanding the mechanisms through which activation of the fibroblast growth factor (FGF) / FGF receptor (FGFR) axis drives breast cancer growth and progression. This research is relevant to human health because understanding the mechanisms driving tumor cell-stromal interactions during the growth and metastasis of human breast cancers will ultimately lead to the development of novel therapeutic strategies that will improve patient outcome by enhancing initial response, preventing resistance and reducing relapse.

PI_NAMEs: SCHWERTFEGER, KATHRYN L (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: aggressive breast cancer;autocrine;Automobile Driving;Biological Assay;bone;Breast Cancer Cell;Breast Cancer Model;Breast Cancer Patient;breast cancer progression;cancer cell;Cancer Etiology;Cell Communication;Cell Culture Techniques;Cholesterol;Cholesterol Esters;Cholesterol Homeostasis;clinically relevant;Coculture Techniques;Data;Development;Disease;Environment;Esterification;Exhibits;experimental study;FGFR1 gene;Fibroblast Growth Factor;Fibroblast Growth Factor Receptors;Gene Expression;Generations;Genetic;Genetic Transcription;Goals;Growth;Health;Human;Imaging Techniques;immunosuppressive macrophages;improved;inhibitor;Ligands;Link;lipid metabolism;Lipids;Liver;Macrophage;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Mediating;Mediator;Metabolic;Metabolic Pathway;Modeling;mouse model;multiplexed imaging;Mus;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;novel therapeutic intervention;paracrine;Pathway interactions;patient subsets;Patient-Focused Outcomes;Physiological;Population;prevent;promoter;receptor;Receptor Activation;Receptor Signaling;Regulation;Relapse;Research;Resistance;response;Sampling;Signal Pathway;Site;SRE-2 binding protein;Sterol O-Acyltransferase;sterol O-acyltransferase 2;Stromal Cells;Stromal Neoplasm;targeted treatment;Testing;Therapeutic;Tissues;transcriptomics;translational impact;Treatment Efficacy;triple-negative invasive breast carcinoma;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;tumor-immune system interactions;tumorigenic;Women's mortality

PROJECT_TITLE: Contributions of FGFR-Mediated Tumor-Stromal Interactions to Breast Cancer Growth and Progression

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Digestive Diseases;Digestive Diseases - (Gallbladder);Liver Disease;Patient Safety;Prevention

ORG_CITY: PALO ALTO

ORG_NAME: KOLI, INC.

PHR: Gallstones are present in up to 25% of adults. Approximately 1% to 4% of people with gallstones develop symptoms and complications such as acute cholecystitis, obstructive jaundice, or pancreatitis. Surgery is currently the only definitive solution. Unfortunately, a timely operation is not always an option. Patients may be unable to tolerate surgery due to other medical conditions and risk the chance of a recurrence while surgery is delayed. Kōli is a medical device company developing a novel implantable device to prevent recurrent obstruction in patients with gallstone disease without surgery.  This Direct to Phase II award will fund advanced development of the filtering system, including incorporation of an innovative micro surface textured coating to replace the current barbed metal anchors, integration of radiopaque tantalum markers, and validation of the updated system in bench and large animal studies.

PI_NAMEs: CHENG, CHRISTOPHER  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Abdominal Pain;Acute Cholecystitis;Address;Adult;Advanced Development;Adverse event;adverse outcome;Affect;Age;Animals;Antibiotics;Area;Award;Bile fluid;biliary tract;Body Weight decreased;Capital;Cholecystectomy;Cholelithiasis;Cholesterol;Chronic;Cicatrix;Clinical;clinical practice;commercialization;common treatment;comorbidity;Complication;Consumption;Crohn's disease;design;Devices;Diabetes Mellitus;Duct (organ) structure;effective therapy;Elderly;Emergency Situation;Excision;Failure;Family;Fasting;Feasibility Studies;Film;first-in-human;Fluoroscopy;Funding;Gallbladder;gallstone disease;Gastroenterology;General Anesthesia;grasp;Heart Diseases;high risk;Histopathology;Hormone replacement therapy;human old age (65+);Implant;implantable device;Incidence;Infection;Inflammation;innovation;Intervention;Interventional radiology;Investments;Legal patent;Life;Lung Diseases;manufacture;Mechanics;Medical;Medical Device;Metals;migration;minimally invasive;Modeling;Morbidity - disease rate;mortality;Myocardial Infarction;Neck;novel;obese person;Obstruction;Obstructive Jaundice;operation;Operative Surgical Procedures;Organ;Outpatients;Pancreatitis;Patient observation;Patients;Pattern;Penetration;Perforation;Performance;Persons;Phase;Philippines;Polyurethanes;porcine model;Positioning Attribute;Pregnancy;Pregnant Women;prevent;Privatization;Procedures;programs;prototype;radiologist;Recording of previous events;Recurrence;Reporting;Risk;Risk Factors;Safety;Sampling;Schedule;Sepsis;Series;Small Business Innovation Research Grant;Small Intestines;Solid;Stroke;Surface;Symptoms;System;Tantalum;Techniques;Technology;Testing;Texture;Time;Tissues;Traction;ultrasound;United States;Update;Validation;Vomiting;Wait Time;western diet;Woman;Work

PROJECT_TITLE: Koli: A non-surgical solution for gallstone disease


NIH_SPENDING_CATS: Cancer;Skin Cancer

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Interactions between melanoma cells and the tumor microenvironment have important implications for tumor progression and metastasis. Melanoma cells and adipocytes closely interact at the tumor-fat interface, but the mechanism of melanoma-adipocyte communication is poorly understood. In this study, we aim to determine how melanoma cells and adipocytes interact and the role of this crosstalk in melanoma progression.

PI_NAMEs: PERLEE, SARAH  (contact)

PROJECT_TERMS: Adhesions;Adipocytes;Adipose tissue;Attention;autocrine;Binding;Biological Assay;cancer cell;cancer therapy;Cell Adhesion Molecules;Cell Communication;Cell Line;Cell Physiology;cell type;Cell-Cell Adhesion;Cells;Coculture Techniques;Communication;Communications Media;Connexin 43;connexin 45;Connexins;Coupled;Coupling;CRISPR/Cas technology;Cyclic AMP;Cyclic Nucleotides;Data;Dermal;Disease;Distant;Dyes;Endothelial Cells;Engineering;Fatty acid glycerol esters;Fatty Acids;Fibroblasts;Fishes;Gap Junctions;Goals;Growth;Human;Immunofluorescence Immunologic;Immunohistochemistry;In Vitro;in vivo;in vivo Model;insight;intercellular communication;Intercellular Junctions;Invaded;Ions;keratinocyte;Knock-out;Knowledge;Lipase;Lipids;Lipolysis;Malignant Neoplasms;MCAM gene;Mediating;Mediator;Melanoma;Melanoma Cell;Melanoma Tumor;Metabolic Pathway;Molecular;Neoplasm Metastasis;new therapeutic target;Organ;Outcomes Research;paracrine;Pathway interactions;Patients;Phosphorylation;Play;Process;Protein Isoforms;Proteins;Role;Signal Pathway;Signaling Molecule;Skin;Skin Cancer;Source;subcutaneous;Subcutaneous Tissue;System;Testing;theories;transcriptome sequencing;transplant model;Triglycerides;tumor;Tumor Cell Invasion;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;tumorigenesis;Work;Zebrafish

PROJECT_TITLE: Investigating the role of melanoma-adipocyte cell junctions in heterotypic communication and tumor progression


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Narrative Development of disruptive hybrid proteomics pipeline technologies to revolutionize antibody discovery, characterization, analysis and applications.

PI_NAMEs: SHI, YI  (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TITLE: Development of the next generation antibody technologies and their applications

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

PHR: Core A Project Narrative The Administrative Core will oversee the administrative responsibilities of the various laboratory studies outlined in the three Projects, by providing high-level organizational support for the Projects. These include provision of necessary resources, fiscal oversight, adherence to institutional and NIH guidelines/regulations, and the coordination of regular joint meetings to disseminate results, discuss scientific challenges, and discover innovative solutions to advance the science. The Administrative Core will further promote the rapid dissemination of significant research findings to the scientific community.

PI_NAMEs: WU, CATHERINE JU-YING (contact)

PROJECT_TERMS: Address;Adherence;Administrative Coordination;Allogenic;Biology;Chronic Lymphocytic Leukemia;Clinical;clinical care;Clinical Trials;combinatorial;Communication;Communities;Data Collection;data dissemination;data sharing;Dedications;Disease remission;disorder subtype;Dissection;Factor Analysis;Fostering;Generations;Genome;Genomics;Goals;Guidelines;Hematopoietic;Heterogeneity;Immunotherapy;improved;individual patient;innovation;Institution;Joints;Laboratory Study;Maintenance;Malignant Neoplasms;Maps;meetings;member;Molecular;Motivation;mouse model;novel;novel therapeutics;Outcome;Patient Care;Patient-Focused Outcomes;Patients;phenome;programs;prospective;Proteomics;Regulation;Research;Research Personnel;Resolution;Resource Sharing;Resources;Retrieval;Richter's Syndrome;sample collection;Sampling;Science;Services;stem;Stem cell transplant;targeted agent;Therapeutic;Tissue Sample;translational goal;Translations;United States National Institutes of Health;Vision

PROJECT_TITLE: Administrative Core


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

PHR: PROJECT NARRATIVE  The proposed studies will fill the knowledge gap in understanding the biomechanical interplay between peripapillary sclera and optic nerve head, a critical factor influencing the eye’s mechanical susceptibility to intraocular pressure. Combined with the development of a translatable technique to image such interplay in vivo, this knowledge will lay the groundwork for developing novel diagnostic and therapeutic strategies to better mitigate glaucoma-related vision loss.

PI_NAMEs: LIU, JUN  (contact)

PROJECT_TERMS: 3-Dimensional;3D ultrasound;Address;Affect;African American;Aftercare;Age;American;Animal Model;Axon;axon injury;Biochemical;Biomechanics;Blindness;collagenase;combat;Complex;computer studies;Data;Development;diagnostic strategy;elastography;Extracellular Matrix;Eye;Family suidae;feasibility testing;Foundations;genipin;Glaucoma;Human;human old age (65+);Image;imaging modality;Imaging Techniques;in vivo;Individual;Influentials;innovation;Knowledge;Length;Measurement;Measures;Mechanical Stress;Mechanics;modifiable risk;Modification;Modulus;Myopia;nerve damage;neural;novel;novel diagnostics;novel therapeutic intervention;Optic Disk;Optic Nerve;optic nerve disorder;Optical Coherence Tomography;optical imaging;Papillary;Patients;Penetration;Persons;Physiologic Intraocular Pressure;Placebos;Play;porcine model;power analysis;Predisposition;Property;Public Health;Race;Radial;radio frequency;Randomized;Recording of previous events;Resolution;response;retinal imaging;Risk;Risk Factors;Role;Sample Size;Sclera;Stress;submicron;success;Techniques;Testing;Thick;Tissues;treatment effect;treatment group;treatment response;treatment strategy;ultrasound;Vision

PROJECT_TITLE: Biomechanical Interplay between Optic Nerve Head and Peripapillary Sclera


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Dental, Oral, and Craniofacial Disease;Genetics;Hematology;Human Genome;Precision Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Clonal blood disorders exhibit overproduction or underproduction of blood components and develop upon the acquisition of genetic mutations in genes involved in cell signaling and other cellular processes. Recently, we developed a novel tool that can sequence many genes in individual cells (‘single-cell sequencing’), by which we demonstrated that these mutations alter the cells uniquely in different types of blood cells. Now, we seek to study how other factors that are critical for blood cell development, like modifiers of DNA (‘epigenetics’) and the bone marrow environment, affect the changes induced by the gene mutations to impact clinical pictures, by developing and applying innovative single-cell sequencing technologies.

PI_NAMEs: NAM, SEUNG HA  (contact)

PROGRAM_OFFICER_NAME: MILLER, BECKY

PROJECT_TERMS: Acceleration;Admixture;Advisory Committees;Affect;Anatomy;Appointment;biobank;Biochemical;Biological Assay;Biomedical Research;Blood;Blood Cells;Bone Marrow;calreticulin;CD34 gene;Cell Cycle;Cell Physiology;Cell surface;cell type;Cells;Chromatin;Clinical;clinical phenotype;clinical training;college;Communities;Complex;Core Facility;cytokine;Data;Dependence;Development;Diagnostic;Disease;disease phenotype;DNA;DNA Sequence Alteration;doctoral student;driver mutation;Environment;Environmental Risk Factor;Epigenetic Process;epigenome;epigenomics;Exhibits;Faculty;forging;Funding;Gene Expression Profile;Gene Mutation;Genes;Genetic;Genetic Transcription;Genome;Genomic medicine;Genomics;Genotype;Hematological Disease;Hematopathology;Hematopoiesis;Hematopoietic;hematopoietic differentiation;Hematopoietic Neoplasms;Hematopoietic stem cells;Human;Immune;Immunologic Factors;immunomodulatory therapies;improved;Individual;innovation;Inorganic Chemistry;insight;Institution;Intrinsic factor;Investigation;Laboratories;Link;Malignant - descriptor;medical schools;medical specialties;Medicine;Megakaryocytes;Memorial Sloan-Kettering Cancer Center;Mentors;Modernization;Molecular;molecular array;Molecular Genetics;Morphology;mouse model;MPL gene;multidisciplinary;multiple omics;mutant;Mutate;Mutation;Myelogenous;Myeloproliferative disease;Nature;neoplastic;neoplastic cell;Neoplastic Processes;New York;next generation;NF-kappa B;novel;Outcome;Output;Pathology;Pathway interactions;Patients;Peer Review;personalized medicine;Physicians;Population;Process;Production;progenitor;programs;Protein Secretion;Proteins;Publications;Research;Research Personnel;Research Training;Resources;response;Sampling;Scientific Advances and Accomplishments;Scientist;Shapes;Signal Transduction;single cell genomics;single cell sequencing;skills;Somatic Mutation;Specimen;stem cell function;stem cells;T-Lymphocyte;targeted treatment;Technology;Testing;Therapeutic Intervention;Tissues;tool;Training;transcription factor;transcriptome;transcriptomics;Translational Research;Trees;undergraduate student;United States National Institutes of Health

PROJECT_TITLE: Defining malignant hematopoiesis via single-cell multi-omics

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-H(70)R]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Rare Diseases

PHR: Narrative Core 1 will generate a large repository of molecularly and clinically-annotated primary samples from patients with Richter's syndrome and patients with chronic lymphocytic leukemia at high risk of developing Richter's syndrome. These primary samples will be obtained from patients on and off clinical trials at our center and will include extensive collection of cell-free DNA designed for early detection of RS. Samples from this Core will be efficiently distributed to the Projects to provide the primary patient material essential to elucidating the pathogenesis and therapeutic vulnerabilities of Richter's syndrome.

PI_NAMEs: DAVIDS, MATTHEW S (contact)

PROJECT_TERMS: Award;biobank;Biology;Biopsy;Bone Marrow;Bone marrow biopsy;cell bank;cell free DNA;Cells;Chronic Lymphocytic Leukemia;Clinical;Clinical Trials;Collection;Data;design;Development;Dissection;Doctor of Philosophy;Early Diagnosis;Ensure;Evaluation;Event;Foundations;Future;Genetic;Genome;high risk;improved;improved outcome;Infrastructure;Institution;lymph nodes;Methods;Mission;Molecular;Molecular Profiling;Mononuclear;novel;novel marker;Nucleic Acids;participant enrollment;Pathogenesis;patient prognosis;Patient-Focused Outcomes;Patients;peripheral blood;phenome;Plasma;Process;Prognosis;programs;Reporting;repository;Resources;Richter's Syndrome;Risk;sample collection;Sampling;Science;Site;standard of care;System;Therapeutic;therapeutic target;Time;timeline;tissue resource;Tissues;Translational Research;treatment trial

PROJECT_TITLE: Biospecimens


NIH_SPENDING_CATS: Chronic Pain;Neurosciences;Opioids;Pain Research;Physical Injury - Accidents and Adverse Effects;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: Project Narrative: Mechanisms that maintain any form of chronic pain remain mysterious, which helps explain the limited effectiveness of current treatments. This joint project will define mechanisms in injury-detecting sensory neurons that contribute to life-long chronic pain after spinal cord injury. It follows up on discoveries that spinal cord injury causes a large number of these sensory neurons to change from their normal state of electrical silence into a persistent state of spontaneous activity, and that these alterations are linked both to reduced responsiveness to opioids and to synergistic cell signaling mechanisms that offer novel targets for treating chronic pain.

PI_NAMEs: DESSAUER, CARMEN W. (contact);WALTERS, EDGAR T.

PROGRAM_OFFICER_NAME: GREENWELL, THOMAS

PROJECT_TERMS: A kinase anchoring protein;Action Potentials;Acute;Address;Afferent Neurons;Animals;Biochemistry;C Fiber;cannabinoid receptor;Cell membrane;Cellular biology;Central Nervous System;Chronic;chronic pain;chronic pain management;Complex;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;Drug Combinations;Drug Screening;drug testing;Effectiveness;Electrophysiology (science);endogenous opioids;experimental study;Exposure to;FDA approved;Funding;Goals;Hyperactivity;Image;Imaging Device;In Vitro;in vivo;in vivo evaluation;Injury;Joints;KRAS2 gene;Laboratories;Link;Lipids;MAP Kinase Gene;Measures;Mediating;Membrane Lipids;Membrane Potentials;Microscopy;Modeling;nanocluster;Neurons;neurotrophic factor;Nociceptors;novel;Opioid;Opioid Receptor;Pain;painful neuropathy;Pathway interactions;Peripheral;Persistent pain;Pharmaceutical Preparations;Phosphatidylserines;Phosphorylation;Phosphorylation Site;Proteins;RAS inhibition;Ras/Raf;Rattus;recruit;Refractory;Reinforcing Factor;Resistance;response;Rest;Role;scaffold;severe injury;Signal Transduction;Spinal cord injury;Spinal cord injury patients;Spinal Ganglia;spontaneous pain;Stimulus;Testing

PROJECT_TITLE: Mechanisms of cAMP signaling that drive spontaneous activity in nociceptors

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy

ORG_CITY: NEW HAVEN

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE: Cancer cells are prone to genomic instability that can lead to exposure of genomic DNA to the cytosol, where it can be recognized by cytosolic DNA sensors and trigger an innate immune response. However, the mechanisms by which cytosolic DNA sensors such as cGAS are regulated, especially in response to aberrant exposures of self DNA in cancer, is unclear. Therefore, this proposal intends to define the role of novel regulators of the cGAS/STING innate immune response to inform targeted interventions to cancer.

PI_NAMEs: ISENHOUR, ANTHONY WAYNE (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Auxins;Biochemical;Cancer Biology;cancer cell;Cancer cell line;career;Cell Line;Cellular biology;Chromatin;chromosome missegregation;Chromosomes;Clupeidae;Complex;CRISPR/Cas technology;Cyclic GMP;Cytosol;Data;Data Analyses;Dedications;Defect;design;DNA;DNA Binding;DNA Repair Pathway;DNA-Binding Proteins;Electron Microscopy;Endosomes;env Gene Products;Enzyme-Linked Immunosorbent Assay;experimental study;Exposure to;Fluorescence Microscopy;Gene Expression;Genes;Genetic;Genomic DNA;Genomic Instability;Goals;Home;Immune signaling;Immunofluorescence Immunologic;Immunotherapeutic agent;Individual;innate immune pathways;Innate Immune Response;insight;Interferons;Interphase;Intervention;Learning;light microscopy;live cell imaging;Malignant Neoplasms;Measures;Membrane Proteins;micronucleus;Mitosis;Modeling;Molecular;novel;Nuclear;Nuclear Envelope;Nuclear Inner Membrane;Outcome;Pathway interactions;Phosphorylation;Production;Productivity;Proteins;Publishing;recruit;Regulation;response;Role;Rupture;Scientist;seal;sensor;Signal Transduction;Site;Sorting;Source;spatiotemporal;Stimulator of Interferon Genes;synergism;System;Testis;Training;Transcript;Transfection;tumor;tumor growth;Tumor Promotion;Western Blotting;Work

PROJECT_TITLE: Determining the role of nuclear envelope reformation proteins in regulating the cGAS/STING innate immune response in cancer


ADMINISTERING_IC: AG

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Nutrition;Physical Activity;Prevention

ORG_CITY: MILWAUKEE

ORG_NAME: MARQUETTE UNIVERSITY

ORG_STATE: WI

PHR: PROJECT NARRATIVE Pre-diabetes (Pre-D) is a precursor to type 2 diabetes (T2D) and characterized by increased exercise fatigability of lower limb muscles, that can impede exercise performance. The cause for the increased fatigability in people with Pre-D is not known. Given the profound vascular disease present in people who have had uncontrolled diabetes for several years, we will determine whether dynamic, fatiguing contractions of the lower limb muscles in people with Pre-D are limited by vascular dysfunction at multiple levels along the vascular tree including the artery, arteriole, and/or capillary. Furthermore, a novel exercise training regime involving blood flow restriction to the exercising limb will be used as a probe to further understand the vascular mechanisms for increased fatigability in people with Pre-D and T2D. The long-term goal is to better understand what limits exercise and functional performance in people with diabetes to help develop targeted, more effective exercise programs.

PI_NAMEs: HUNTER, SANDRA K;SUNDBERG, CHRISTOPHER  (contact)

PROGRAM_OFFICER_NAME: SERRA, MONICA CHRISTINE

PROJECT_TERMS: Acetylcholine;Adult;Affect;Age;American;Arteries;arteriole;Attenuated;Biological Availability;Biopsy;Blood capillaries;Blood flow;Blood Vessels;Body mass index;Cardiovascular Diseases;Clinical;Clinical Trials;clinically significant;Coupled;Couples;density;Dependence;diabetes control;Diabetes Mellitus;diabetic;diet and exercise;Disease;Doppler Ultrasonography;Educational Intervention;effectiveness evaluation;Endothelium;Exercise;exercise program;exercise training;Extensor;Fatigue;femoral artery;Glucose;Glycosylated Hemoglobin;Goals;Human;Impairment;improved;in vivo;Individual;Insulin;Intervention;Knee;Knowledge;Laboratories;Leg;Limb structure;Lower Extremity;Measures;Mediating;mortality;Muscle;Near-Infrared Spectroscopy;Neuropathy;Nitric Oxide;Non-Insulin-Dependent Diabetes Mellitus;novel;older adult;Oxygen;Participant;Performance;Perfusion;Persons;Physical activity;Physical Exercise;Physical Function;physical impairment;Plasma;Population;Prediabetes syndrome;Prevalence;prevent;protective effect;resistance exercise;response;sex;Site;Skeletal Muscle;skeletal muscle metabolism;Testing;Training;Trees;Ultrasonography;Vascular Diseases;Vascular Endothelium;vastus lateralis;Video Microscopy;young adult

PROJECT_TITLE: Mechanisms of Fatigability and the Protective Effects of Exercise in People with Diabetes

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Rare Diseases

PHR: Project Narrative The mission of the Pathology Core (2) is to characterize and bank tumor samples from RS patients representing a full range of biologic characteristics, as well as from engineered RS mouse models of disease. This tissue resource will enable the fundamental discoveries required to understand the pathogenesis of the disease and move toward improved therapies and eventual cure. As part of this effort, the Pathology Core will provide central review and resources for human and mouse RS pathology and generate a bank of patient-derived RS-PDX primagraft models, which would serve as an extraordinary resource for this study of RS.

PI_NAMEs: CARRASCO, RUBEN D (contact)

PROJECT_TERMS: Address;Area;Automobile Driving;B-Cell Antigen Receptor;Biologic Characteristic;Biological;Biology;biomarker identification;Biopsy;candidate validation;cell bank;Cell Line;Cells;Chemotherapy-Oncologic Procedure;chromosome 13q loss;Chronic Lymphocytic Leukemia;Clinical;Clinical Trials;Collaborations;Complication;Credentialing;Data;del(17p13);design;Development;Diagnosis;Diagnostic;Disease;disease model;Dissection;Doctor of Philosophy;Documentation;Drug resistance;effective therapy;Engineering;Engraftment;Evaluation;experimental study;Fibrous capsule of kidney;Formalin;Foundations;Freezing;Future;Genetic;Genetic Polymorphism;Genome;genome editing;Genomics;Goals;Grant;Hematologic Neoplasms;Hematopathology;Hematopoietic stem cells;Histologic;Histopathology;Human;Human Resources;Immunocompromised Host;Immunodeficient Mouse;Immunohistochemistry;Implant;implantation;improved;In Vitro;in vivo;in vivo Model;Infrastructure;Injections;innovation;Institution;interest;large cell Diffuse non-Hodgkin's lymphoma;Lesion;lymphoid neoplasm;Lymphoma;Malignant Neoplasms;Mission;Modeling;Molecular;Morphology;mouse model;MS4A1 gene;Mus;novel;novel marker;Operative Surgical Procedures;Paraffin Embedding;participant enrollment;Pathogenesis;Pathologic;Pathology;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;phenome;Phenotype;pre-clinical;Preparation;Procedures;Process;programs;prospective;Proteomics;PTPRC gene;Receptor Gene;Refractory;Reporting;Research;Research Personnel;Research Support;Resources;Rest;Richter's Syndrome;Risk;sample archive;Sampling;Signal Transduction;Site;Slide;Small-Cell Lymphoma;Solid;Specimen;Stereotyping;Study Section;subcutaneous;Tail;Testing;therapeutic target;Tissue Microarray;tissue resource;Tissues;tool;transcriptomics;Translations;Transplantation;treatment response;tumor;Tumor Bank;tumor microenvironment;Validation;Variant;Veins

PROJECT_TITLE: Pathology


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: ARLINGTON

PHR: PROJECT NARRATIVE Project Title: Long-Term Improvements to the National Animal Food Safety System Through Integration, Strengthened Collaboration, Improved State Regulatory and Surveillance Protection Programs, and Promotion of the Animal Feed Regulatory Program Standards Under an initial 5-year cooperative agreement from FDA, considerable progress has been made toward modernization of the national animal food safety system as envisioned by the Food Safety Modernization Act (FSMA). The work outlined in this project proposal will continue the important joint efforts of AAFCO, NASDA, and FDA as they work together on continuous improvement of the national animal food safety system and promotion of the Animal Feed Regulatory Program Standards (AFRPS).

PI_NAMEs: REARDON, JOE  (contact)

PROGRAM_OFFICER_NAME: ISAKSON, ISAIAH

PROJECT_TITLE: NASDA Foundation and AAAFCO, Long-Term Improvements to the National Animal Food Safety System and Promotion of the Animal Feed Regulatory Program Standards (AFRPS)


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Precision Medicine;Rare Diseases

PHR: Narrative The overarching goal of the Proteomics Core (Core 3) is to provide state-of-the-art, mass spectrometry-based- proteomics and phosphoproteomics data and analyses in support of Projects 1-3; proteomics data will help to identify cancer-relevant pathways triggered by somatic DNA variants or DNA copy number alterations (CNAs) and help to narrow target selection for potential therapeutic intervention of Richter's syndrome and related cancers. The resulting proteomic data, including the critical quantitative and site-specific modification information, will be computationally analyzed and integrated with personalized genomic data using bioinformatics tools integrated into the cloud-based pipeline PANOPLY. To enable more rapid and specific analyses of proteins and phosphopeptides targets of interest emerging from the discovery experiments, the proteomics core will develop high sensitivity targeted MS assays and apply these to analyze human biospecimens and preclinical samples in native and drug-perturbed states.

PI_NAMEs: CARR, STEVEN A (contact)

PROJECT_TERMS: Acceleration;Amino Acids;Apoptotic;B-Lymphocytes;Biocompatible Materials;biocomputing;bioinformatics tool;Biological Assay;Blood;cancer cell;Cells;Chronic Lymphocytic Leukemia;cloud based;Communities;Data;data integration;Data Set;Dependence;Disease;Disease Progression;Dissection;DNA;DNA copy number;Doctor of Philosophy;experimental study;Functional disorder;Gene set enrichment analysis;Genes;Genome;genomic data;Genomics;Goals;Guidelines;Human;improved;insight;interest;Investigation;Label;large cell Diffuse non-Hodgkin's lymphoma;Liquid Chromatography;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Measures;Messenger RNA;Methods;Modification;Molecular;molecular sequence database;mouse model;multiple omics;Mus;Mutation;novel;Pathway Analysis;Pathway interactions;Patient-Focused Outcomes;Patients;Peptides;personalized genomics;Pharmaceutical Preparations;Phase;phenome;Phosphopeptides;Phosphoproteins;phosphoproteomics;Phosphorylation;Post Translational Modification Analysis;Post-Translational Protein Processing;pre-clinical;Pre-Clinical Model;profiles in patients;Protein Analysis;Protein Isoforms;Proteins;proteogenomics;Proteome;Proteomics;Relapse;Resistance;Resources;response;Richter's Syndrome;RNA;RNA Splicing;Sampling;Signal Transduction;Site;Solid Neoplasm;Specificity;stable isotope;Stable Isotope Labeling;Structure;tandem mass spectrometry;targeted treatment;Technology;Therapeutic Intervention;therapy resistant;Transcript;transcriptomics;treatment response;tumor;Variant;Work

PROJECT_TITLE: Proteomics


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE - Core 4 Biostatistics The goal of Core 4 Biostatistics is to assure that all experiments conducted through this P01, centered around chronic lymphocytic leukemia and Richter's Syndrome, have access to state-of-the-art statistical support for their design and analysis. This extends to the basic science and murine experiments described as well as to the clinical and correlative studies undertaken by all the Projects, as well as the Cores. This assures that the work performed on this P01 will be robust and reproducible, and thereby contribute to an improved understanding of these diseases.

PI_NAMEs: ARYEE, MARTIN JOSEPH ANKRAH (contact)

PROJECT_TERMS: Animal Experimentation;Animals;Basic Science;Biological Assay;Biometry;Blinded;Chronic Lymphocytic Leukemia;Clinical;Clinical Data;Clinical Research;Correlative Study;Data;Data Set;design;Disease;Dissection;Epigenetic Process;experimental analysis;experimental study;Genetic;Genome;Germ Lines;Goals;improved;insight;Laboratories;Laboratory Research;member;Molecular;Mus;Mutation;novel;novel therapeutics;Outcome;Patient-Focused Outcomes;Patients;personalized therapeutic;Pharmaceutical Preparations;phenome;programs;Proteomics;repository;Reproducibility;Research Personnel;Research Project Grants;research study;Resistance;Resources;response;Richter's Syndrome;Sampling;Services;single cell analysis;single cell technology;Source;Techniques;Therapeutic Studies;tumor;Work

PROJECT_TITLE: Biostatistics