ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Biotechnology;Clinical Research;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Rheumatoid Arthritis

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Narrative We will develop advanced machine learning approaches to combine single-cell multiomic and bulk 3D interactome data to model the impact of genetic variation on gene regulation, using rheumatoid arthritis (RA) as a disease model. Our gene regulatory models and experimental analyses will focus on two cell types that drive RA tissue pathology—T cells and synovial fibroblasts—and will serve as a case study for examining the genetics of polygenic human diseases that dysregulate multiple interacting cell types within affected tissues.

PI_NAMEs: LESLIE, CHRISTINA S (contact);RUDENSKY, ALEXANDER Y

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: 3-Dimensional;Affect;Alleles;Antigen-Presenting Cells;arthropathies;Autoimmune;autoimmune inflammation;Case Study;CAST/EiJ Mouse;Cell Communication;cell community;Cell model;Cell Physiology;cell type;Cells;Clinical;Complex;connectome;Data;Degenerative Disorder;Development;Disease;disease model;disease phenotype;Distant;empowerment;Enhancers;epigenetic regulation;epigenome;Etiology;experimental analysis;experimental study;Fibroblasts;Functional disorder;functional genomics;Gene Expression;Gene Expression Regulation;gene network;gene regulatory network;Genes;Genetic;Genetic Polymorphism;genetic variant;Genetic Variation;Genome;genomic locus;genomic variation;Genomics;Goals;Hereditary Disease;Heterogeneity;Human;human data;human disease;Hybrids;Immune;Immunology;In Situ;Inflammation;Inflammatory;intercellular communication;joint inflammation;Joints;Knowledge;Laboratories;Learning;learning strategy;Link;Machine Learning;machine learning framework;machine learning model;Metabolic Diseases;Modeling;Molecular;mouse genetics;multiple omics;Mus;Nature;network models;novel;Organizational Models;parallelization;Pathology;Patients;Phenotype;Polygenic Traits;predictive modeling;Primary Cell Cultures;Process;programs;Public Health;Regulation;Regulator Genes;Regulatory Element;Rheumatoid Arthritis;Sampling;sedentary;Specific qualifier value;System;T cell regulation;T-Cell Activation;T-Lymphocyte;Technology;Tissues;Training;training data;transcription factor;Transcriptional Regulation;transcriptome;transcriptomics;transfer learning;Variant

PROJECT_TITLE: Deciphering the Genomics of Gene Network Regulation of T Cell and Fibroblast States in Autoimmune Inflammation


ADMINISTERING_IC: NS

ARRA_FUNDED: N

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The Developmental Neurology Training Program supports postdoctoral fellows in the laboratories of neuroscientists at Boston Children's Hospital and related institutions in the Harvard Medical Area. The trainees are engaged in ground-breaking research into the molecular mechanisms underlying brain development, including studies of autism, epilepsy, Rett syndrome, spinomuscular atrophy, muscular dystrophy, and tuberosclerosis. With significant attention to the skills needed for rigorous studies, the trainees are prepared for careers in fundamental research that are informed by clinical needs.

PI_NAMEs: ENGLE, ELIZABETH C.;SCHWARZ, THOMAS L. (contact)

PROGRAM_OFFICER_NAME: WEIGAND, LETITIA ALEXIS

PROJECT_TERMS: Development;Neurology

PROJECT_TITLE: Developmental Neurology


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Hypertension;Lung;Neurosciences;Obesity;Physical Activity;Prevention;Sleep Research

ORG_CITY: TUCSON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative 150 minutes of moderate intensity exercise/week has well-documented benefits for lowering blood pressure (BP) and improving cardiovascular health. However, we have compelling preliminary data showing that only 5 min/day of inspiratory muscle strength training (IMST) over 6 weeks lowered resting systolic BP (SBP) by ~12 mmHg. While IMST could be applied to almost any population, here we seek to establish the efficacy of IMST as an intervention to reduce SBP in the context of obstructive sleep apnea (OSA) -- an increasingly prevalent disorder among older adults accompanied by hypertension, obesity and exercise intolerance.

PI_NAMEs: BAILEY, E. FIONA (contact)

PROGRAM_OFFICER_NAME: RADZISZEWSKA, BARBARA

PROJECT_TERMS: Acute;Adherence;Adult;Advocate;Aerobic Exercise;airway obstruction;Antioxidants;Apnea;arterial stiffness;Ascorbic Acid;Biopsy;Blood Pressure;blood pressure reduction;Blood Vessels;brachial artery;Cardiac Output;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cell Culture Techniques;Chronic;Clinical Treatment;Clinical Trials;clinically relevant;clinically significant;Continuous Positive Airway Pressure;Data;Development;Diastolic blood pressure;Disease;Double-Blind Method;efficacy evaluation;Elasticity;Endothelial Cells;endothelial dysfunction;Endothelium;Event;evidence base;Exercise;exercise intensity;exercise intolerance;Fatigue;Femur;Guidelines;Health;Heart Rate;Hour;Human;Hyperactivity;Hypertension;hypertension treatment;Hypoxemia;improved;in vivo;indexing;Inflammation;Inflammatory;inflammatory marker;Infusion procedures;insight;Interleukin-10;Interleukin-6;Intervention;Measures;Mediating;men;Methods;Modeling;Molecular;molecular marker;Muscle;muscle strength;Nerve;Nitric Oxide;Norepinephrine;novel;Obesity;Obstructive Sleep Apnea;older adult;Overweight;Oxidative Stress;Patients;peer;Peripheral Resistance;Physiologic pulse;Placebo Control;Placebos;Plasma;Population;preservation;pressure;Prevalence;Prevention strategy;Production;Randomized;randomized placebo-controlled clinical trial;Reactive Oxygen Species;Research;response;Rest;Safety;sedentary;Serum;Signal Transduction;Sleep Apnea Syndromes;Snoring;Source;strength training;Superoxides;Sympathetic Nervous System;Time;tool;Training;trial comparing;Umbilical vein;United States;Vasoconstrictor Agents;Woman;young adult

PROJECT_TITLE: Time-efficient inspiratory muscle strength training for improving blood pressure and vascular function in older adults with sleep-disordered breathing

STUDY_SECTION: CICS

STUDY_SECTION_NAME: Clinical and Integrative Cardiovascular Sciences Study Section[CICS]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Services;Palliative Care

ORG_CITY: PITTSBURGH

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative: The proposed project addresses a major public health problem that arises in the care of patients with incurable malignancies: failure to deliver end-of-life (EOL) care consistent with patients' needs, values and preferences. The purpose of this trial comparing the effectiveness of (1) in-person, facilitated advance care planning versus (2) web-based advance care planning is to identify the best approach to improve treatment decisions near EOL and ensure patients' wishes are honored. Data from this study will inform clinicians, payers and health systems seeking to adopt and scale the most effective and efficient ACP strategy in real-world oncology settings, with the potential to improve care for the over 600,000 Americans who die annually from cancer and their families. 3

PI_NAMEs: SCHENKER, YAEL  (contact)

PROGRAM_OFFICER_NAME: STRECK, BRENNAN PARMELEE

PROJECT_TERMS: Academy;Address;Adopted;Advance Care Planning;advanced directive;Advanced Malignant Neoplasm;American;American Society of Clinical Oncology;Anxiety;anxiety symptoms;Attention;Behavior Therapy;cancer care;Cancer Center;Cancer Patient;care delivery;Caregivers;Caring;chemotherapy;clinical care;comparative effectiveness;comparative effectiveness trial;compare effectiveness;comparison intervention;Consensus;cost;Data;depressive symptoms;design;Effectiveness;effectiveness evaluation;end of life;end of life care;Ensure;evidence base;experience;Failure;Family;Family Caregiver;Family Physicians;Future;Goals;health care service utilization;Health system;Home;hospice utilization;Hospitalization;implementation cost;implementation evaluation;improved;Infrastructure;innovation;International;Intervention;Intervention Trial;Interview;Investments;Malignant Neoplasms;Measures;Medicine;Methods;Modeling;Oncology;Online Systems;Outcome;Patient Care;patient oriented;Patient Outcomes Assessments;Patient Preferences;Patient-Centered Care;Patients;peace;Persons;post-traumatic stress;preference;primary outcome;Public Health;Qualitative Evaluations;Qualitative Research;Quality of Care;randomized trial;relative effectiveness;Reporting;Research;Research Methodology;Resources;Single-Blind Study;System;Time;Training;trial comparing;Writing

PROJECT_TITLE: Patient-centered and efficacious advance care planning in cancer: the PEACe comparative effectiveness trial

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-NRCS-V(08)]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Clinical Research;Mental Health;Neurosciences;Pain Research;Patient Safety;Prevention;Social Determinants of Health

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE Approximately 20-30% of surgical patients are at risk of developing clinically significant Persistent Post-Surgical Pain (PPSP). Our previous studies have revealed that greater pain amplification at baseline, either by psychosocial factors (e.g., anxiety, catastrophizing) or by psychophysical factors (e.g., temporal summation of pain) is quite variable among individuals, is measurable, and is associated with greater PPSP risk. One goal of the proposed studies is to utilize our scalable bedside measurement of a patient’s pain amplification phenotype to screen and identify high-risk patients before surgery, and then to test the ability of targeted interventions to prevent PPSP. Another goal is to gain insight into the mechanisms underlying the development of PPSP in humans, particularly the relationship of the pain amplification phenotype to pro- inflammatory and pro-resolving mediators. As a practicing Anesthesiologist and PhD- trained pain neuroscientist with experience in OR- and lab-based translational studies, I am well-situated to conduct these mechanistic and preventive clinical studies in diverse samples of patients.

PI_NAMEs: SCHREIBER, KRISTIN  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Absence of pain sensation;addiction;Anguish;Anxiety;Award;Basic Science;biopsychosocial;Clinical Research;clinically significant;design;Development;disability;Doctor of Philosophy;experience;Exposure to;Goals;high risk;high risk population;Human;human model;Individual;Inflammatory;Inflammatory Response;insight;Intervention;Longitudinal Studies;Measurable;Measurement;Measures;Mediator;Mental Processes;Nervous System;Neurosciences;non-opioid analgesic;novel;Operative Surgical Procedures;Opioid Analgesics;opioid use;Pain;pain chronification;pain signal;Patients;Perioperative;Persistent pain;Persons;Phenotype;Physical Sufferings;Postoperative Pain;Postoperative Period;Predictive Factor;prevent;Prevention;Prevention strategy;Preventive;Preventive treatment;programs;Psychophysics;psychosocial;Psychosocial Assessment and Care;Psychosocial Factor;Questionnaires;Research;response;Risk;Risk Factors;rumination;Sampling;Sensory;Site;Sleep disturbances;Standardization;Stress;success;System;Testing;Training;Translating;translational study;Variant

PROJECT_TITLE: Personalizing Perioperative Preventive Analgesia: Translational Studies Investigating the Biopsychosocial Underpinnings of Enhanced Pain Propensity


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Autoimmune Disease;Bioengineering;Biomedical Imaging;Brain Disorders;Data Science;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: BALTIMORE

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project narrative. The project provides statistical analysis methods for quantiﬁcation of the evolution in the intensity of brain lesions on multi-sequence Magnetic Resonance Imaging (MRI). Methods are motivated by the need to develop new neuroimaging-based biomarkers for multiple sclerosis (MS), but can be applied to other types of brain diseases including stroke, Alzheimer disease, and cancer.

PI_NAMEs: CRAINICEANU, CIPRIAN M (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Address;Affect;Alzheimer's Disease;Area;Biological Markers;biomarker discovery;biomarker identification;biomarker validation;Biostatistical Methods;Brain;Brain Diseases;Brain imaging;Central Nervous System Diseases;clinical practice;Clinical Research;cognitive disability;Collection;Complex;computer infrastructure;Computer software;Corpus Callosum;Country;Cox Models;Data;Data Set;Dedications;Demyelinations;Dependence;design;Development;Diffusion Magnetic Resonance Imaging;Disease;Evolution;Funding;Grant;gray matter;Health;high dimensionality;Image;Imaging Device;imaging modality;imaging study;Immune;Impaired cognition;Joints;Lesion;Literature;longitudinal analysis;Longitudinal Studies;Magnetic Resonance Imaging;Malignant Neoplasms;massive open online courses;Measures;Mediating;method development;Methodology;Methods;Modeling;multidimensional data;Multiple Sclerosis;Multiple Sclerosis Lesions;neuroimaging;novel;Online Systems;open source;Outcome;Participant;Persons;physical impairment;Process;Reader;Recovery;repository;Reproducibility;Research;Sample Size;scale up;serial imaging;Severity of illness;software development;Statistical Data Interpretation;Statistical Methods;statistics;Stroke;Structure;Techniques;Time;United States;web app;white matter

PROJECT_TITLE: Statistical Methods for Multilevel Multivariate Functional Studies

STUDY_SECTION: BMRD

STUDY_SECTION_NAME: Biostatistical Methods and Research Design Study Section[BMRD]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE: In spite of decades of research and expenditure of billions of dollars, cardiovascular disease (CVD) remains the leading cause of death worldwide and is increasing in incidence as a consequence of global Westernization with subsequent epidemics in obesity, metabolic disease, and diabetes, all of which greatly exacerbate CVD. A central premise of this Basic and Translational Cardiovascular Research Training Program (CVTP) is that these diseases are extremely complex, and that rigorous study of them requires trainees to have a strong foundation of knowledge in basic CV physiology, developmental biology, genetics, genomics, bioinformatics, epigenetics, pathology, systems biology, biomedical engineering, and many other disciplines. The goal of this training program is to provide both pre- and post-doctoral trainees a highly integrated training experience to enable them to be facile in all of these disciplines thus uniquely enabling them to conduct pioneering studies of the pathogenesis of CVD, and to contribute to development of innovative and much more effective ways to treat or prevent them.

PI_NAMEs: ISAKSON, BRANT E (contact);OWENS, GARY K

PROGRAM_OFFICER_NAME: LIDMAN, KARIN FREDRIKSSON

PROJECT_TITLE: Basic Cardiovascular Research Training Grant

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(OA)]


ORG_CITY: NEW ORLEANS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: PROJECT NARRATIVE Brain microvascular dysfunction leads to impairments of neurovascular coupling leading to cognitive dysfunction. Mitochondria are cellular energy sensors and impairments of cellular bioenergetics alter the neurovascular coupling. We believe that selective targeting of endothelial variant of neuronal nitric oxide synthase isoform, as we propose, could benefit the brain by protecting microvasculature from hypoglycemia-induced mitochondrial damage.

PI_NAMEs: KATAKAM, PRASAD V (contact);MOSTANY, RICARDO

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Acute;Animals;Anti-diabetic Drugs;awake;Bioenergetics;Biology;Blood capillaries;Blood Glucose;blood glucose regulation;Blood Vessels;Brain;brain dysfunction;brain endothelial cell;C57BL/6 Mouse;cardiovascular disorder risk;Cardiovascular system;Cells;cerebral microvasculature;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;Cerebrum;Clinical;Cognitive;cognitive function;Complications of Diabetes Mellitus;Coupled;Dangerousness;Data;db/db mouse;Dementia;dementia risk;Diabetes Mellitus;diabetic patient;Diameter;discrimination task;Electron Spin Resonance Spectroscopy;Endothelial Cells;Endothelium;experience;extracellular;Generations;Genus Hippocampus;Hypoglycemia;hypoglycemia unawareness;Impaired cognition;Impairment;in vivo;Injury;Insulin;Insulin-Dependent Diabetes Mellitus;Knock-out;Knockout Mice;Laser Scanning Microscopy;Leptin receptor mutation;Link;Measures;Mediating;Meta-Analysis;Methods;Microvascular Dysfunction;Mitochondria;mitochondrial dysfunction;Modeling;Morbidity - disease rate;mortality;Mus;neglect;Neurons;neurovascular coupling;Nitric Oxide;Nitric Oxide Synthase;Nitric Oxide Synthase Type I;Non-Insulin-Dependent Diabetes Mellitus;NOS1 gene;novel;Oxidative Stress Induction;Oxygen Consumption;Patients;Peripheral;Physiological;Play;Production;Protein Isoforms;Reactive Oxygen Species;Recurrence;Regulation;Research;Respiration;response;Risk;Role;Saline;sensor;side effect;Somatosensory Cortex;Streptozocin;Symptoms;Technology;Testing;Texture;Therapeutic;Time;two-photon;Variant;vascular injury;Vibrissae;Work

PROJECT_TITLE: Cerebral Microvascular Bioenergetics and Neurovascular Coupling

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: NEW YORK

ORG_DEPT: CHEMISTRY

ORG_NAME: CITY COLLEGE OF NEW YORK

ORG_STATE: NY

PHR: Project Narrative Our proposed research focuses on the development of general methods to modify the three-dimensional structure of organic molecules, which will expedite preparation of diverse libraries of biologically active molecules for testing as drug candidates. We aim to devise new drug discovery techniques that permit rapid access to common, high- demand molecular architectures predictably, safely, and inexpensively.

PI_NAMEs: BISCOE, MARK ROGER (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: 3-Dimensional;Architecture;Biological;Biological Assay;Carbon;Chemicals;Coupling;Derivation procedure;Development;drug candidate;drug discovery;enantiomer;interest;Libraries;Medicine;Methods;Molecular;Molecular Structure;novel therapeutics;Pharmacologic Substance;Preparation;Principal Investigator;Process;Reaction;Research;stereochemistry;Structure;Techniques;Testing;three dimensional structure;tool;Transition Elements;Work

PROJECT_TITLE: Stereospecific Cross-Coupling Reactions as a Tool for Three Dimensional Molecular Diversification

STUDY_SECTION: SBCA

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


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Machine Learning and Artificial Intelligence;Neurosciences;Pediatric

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative Intracranial hypertension (ICH) may lead to brain injury, developmental delay or even death in children, but its early identification to prevent potentially severe sequelae is challenging. Current invasive approaches to identify ICH are inaccurate and carry important risks, and its non-invasive evaluation is highly subjective and often inconclusive. In this proposal, we aim to use image analysis and machine learning methods together with a unique CT image dataset to identify and quantify for the first time cranial bone development abnormalities that have been qualitatively observed in patients with ICH and that could substantially improve current evaluation approaches.

PI_NAMEs: PORRAS PEREZ, ANTONIO REYES  (contact)

PROGRAM_OFFICER_NAME: OKI, NOFFISAT

PROJECT_TERMS: Affect;Age;age related;Anatomy;Area;Birth;bone;Bone Density;Bone Development;Bone Resorption;Brain;Brain Injuries;Calvaria;Cephalic;Cessation of life;Child;Childhood;Chronic;Clinical;Clinical Management;Clinical Research;Copper;Craniosynostosis;cranium;Data Set;density;Deposition;Development;Developmental Delay Disorders;Diagnosis;Early identification;Evaluation;Growth;Head;Headache;Hemorrhage;Hydrocephalus;Hypertension;Image;Image Analysis;imaging biomarker;imaging Segmentation;impression;improved;Infection;Intervention;Intracranial Hypertension;Intracranial Hypotension;Intracranial Pressure;Intracranial Sinus Thrombosis;Lesion;Live Birth;Location;machine learning method;machine learning model;Magnetic Resonance Imaging;Measurement;Methods;Minerals;Modeling;Monitor;Neurologic;neurosurgery;Normal Range;Operative Surgical Procedures;Parietal bone structure;Pathology;Patients;Pattern;pediatric patients;Physiologic calcification;Physiologic Ossification;Pilot Projects;Population;pressure;prevent;quantitative imaging;radiological imaging;relapse patients;repaired;Reporting;Reproducibility;Risk;sex;skull base;Spinal Tap;Statistical Models;Surgical sutures;suture fusion;Symptoms;Thick;Thinness;Time;tool;Training;Translating;Validation;Venous;Vomiting;X-Ray Computed Tomography

PROJECT_TITLE: Development of CT image-based cranial bone markers of intra-cranial hypertension

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

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

ORG_CITY: BIRMINGHAM

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: NARRATIVE Strong autofluorescence signal from the retinal pigment epithelium (RPE) has high potential for noninvasive, spatially and molecularly precise early detection, and longitudinal follow-up for AMD clinical trials. Using human donor eyes, we will use high-resolution microscopy and imaging mass spectrometry to localize RPE organelles emitting autofluorescence signal in regions rich in cone or rod photoreceptors, as well as areas in high-risk AMD pathology. With analytic chemistry we will identify the responsible molecules.

PI_NAMEs: ACH, THOMAS ;CURCIO, CHRISTINE A (contact);SCHEY, KEVIN L

PROGRAM_OFFICER_NAME: LEE, PAEK-GYU

PROJECT_TERMS: 3-Dimensional;Address;Adult;Age;Age related macular degeneration;aged;Algorithms;Analytical Chemistry;Anterior;Apical;Area;Automobile Driving;Biological;Biology;Blindness;Cellular biology;chemical property;Choroid;Classification;Clinical;clinical application;clinical imaging;Clinical Trials;Cone;Cytoplasmic Granules;data sharing;density;Detection;Development;diagnostic technologies;Disease;Early Diagnosis;Electron Microscopy;Eye;Fluorescence;fluorescence lifetime imaging;fluorophore;follow-up;Fortification;fovea centralis;Funding;Fundus;fundus imaging;German population;Health;high risk;Histologic;Histology;Human;Image;In Situ;in vivo;Ions;Knowledge;Left;Light;Lighting;Lipids;Lipofuscin;Liquid Chromatography;macula;Maps;mass spectrometric imaging;Measures;Melanins;Melanosomes;member;Microscopy;migration;Molecular;Molecular Profiling;Morphology;multidisciplinary;neovascularization;novel;Older Population;Optic Disk;Optical Coherence Tomography;optical spectra;Organelles;Outcome;Outcome Measure;Pathology;patient population;Peripheral;Photoreceptors;Process;progression risk;Resolution;Retina;Retinal Cone;Retinal Diseases;retinal rods;Rod;Signal Transduction;Site;Solvents;Source;Structure;Structure of retinal pigment epithelium;success;Sucrose;synergism;tandem mass spectrometry;Techniques;Technology;Thin Layer Chromatography;Tissue Donors;Tissue imaging;Tissues;Translating;Validation;Vertebrate Photoreceptors;Visualization

PROJECT_TITLE: A hyperspectral approach to RPE fluorophores in AMD

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


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Brain Disorders;Cerebrovascular;Electronic Nicotine Delivery Systems;Lung;Neurosciences;Prevention;Substance Misuse;Tobacco

ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: Electronic cigarettes have become very popular, especially among adolescent users, yet their long-term effects on brain and cognitive function in relationship to lung injury are essentially unknown. Electronic cigarettes are often used together with alcohol which can further aggravate brain and lung damage. Our preliminary data indicate harmful effects of exposure to electronic cigarettes and alcohol on lung tissue, brain microvessels and neuroinflammation. We propose to study injury mechanisms caused by the combination of electronic cigarettes and alcohol and develop therapeutic interventions to prevent them.

PI_NAMEs: PERSIDSKY, YURI  (contact)

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: 3-Dimensional;Adhesions;Adolescent;Adverse effects;Affect;alcohol exposure;alcohol use disorder;Alcohols;Alveolar;Animal Model;Animals;antagonist;Bacterial Infections;Biological Assay;Blood;Blood - brain barrier anatomy;Blood Vessels;blood-brain barrier disruption;blood-brain barrier function;blood-brain barrier permeabilization;Brain;brain endothelial cell;Brain Injuries;Bronchoalveolar Lavage;C-reactive protein;Cells;cellular targeting;central nervous system injury;Cerebral endothelium;cerebral microvasculature;Cerebrovascular Disorders;Chronic;cigarette smoke;Clinical Research;Cognition;Cognitive;cognitive function;combustible tobacco;cytokine;Data;Devices;Dissection;e-cigarette aerosols;Electronic cigarette;electronic cigarette use;electronic cigarette user;Endothelial Cells;endothelial dysfunction;Endothelium;Epithelial Cells;Evaluation;experimental study;Exposure to;extracellular;feeding;Functional disorder;Generations;Glucose Transporter;Health;Hippocampus;Human;immune activation;Immune response;Immune system;Immunohistochemistry;Impaired cognition;Impairment;improved;In Vitro;in vivo;Individual;Infiltration;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;Inhalation;Injury;innovation;intercellular cell adhesion molecule;knockout animal;Knockout Mice;Knowledge;Leukocytes;Link;Lipids;Long-Term Effects;Lung;lung injury;Macrophage;Magnetic Resonance Imaging;Marketing;Measures;Mediating;Messenger RNA;Metals;Microglia;Mitochondria;mitochondrial dysfunction;multidrug abuse;Mus;Myosin Light Chain Kinase;neuroinflammation;neurotoxic;neurotrophic factor;neutrophil;Nicotine;Organ;Oxidative Stress;P2X-receptor;Pathology;Pathway interactions;Permeability;Phenotype;Phosphotransferases;Play;prevent;Production;Proteins;Publications;Purinoceptor;Reaction;Reactive Oxygen Species;receptor;Receptor Signaling;response;Rho-associated kinase;Role;Safety;Secondary to;Smoking;Structure of parenchyma of lung;System;systemic inflammatory response;Testing;Therapeutic Intervention;Tight Junctions;tissue injury;vaping;Virus Diseases;volunteer;Work

PROJECT_TITLE: Injury of blood brain and alveolar-endothelial barriers caused by alcohol and electronic cigarettes via purinergic receptor signaling

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ORG_DEPT: BIOLOGY

PHR: PROJECT NARRATIVE The bacterial outer membrane serves as a barrier to protect the cell from a wide range of external stresses, but also restricts the uptake of nutrients and other molecules into the cell and thus is a critical bacterial organelle. Understanding outer membrane biogenesis and the mechanisms of transport across the cell envelope will provide fundamental new insights into bacterial cell biology, and has the potential to form the basis of future work that could open up new drug targets for next-generation antimicrobials. Here we will continue our study of a poorly understand family of transporters that are important for the trafficking of lipids and other hydrophobic molecules across the bacterial cell envelope, which will allow us to understand how the outer membrane is assembled and maintained, and how other hydrophobic cargos are moved in and out of the cell.

PI_NAMEs: EKIERT, DAMIAN CHARLES (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: Antibiotic Resistance;Antibiotics;antimicrobial;aqueous;Bacteria;Biochemical;Biological Process;cell envelope;Cell Physiology;Cells;Cellular biology;Chloroplasts;Complex;Cryoelectron Microscopy;Cytoprotection;Dedications;Detergents;Development;Escherichia coli;Family;Future;Genetic;Hydrophobicity;Individual;insight;Lipid Bilayers;lipid transport;Lipids;Mammalian Cell;member;Membrane;membrane biogenesis;new therapeutic target;next generation;Nutrient;Organelles;Pathway interactions;periplasm;Phospholipids;Play;Protein Family;Proteins;Publishing;Research;Stress;Structure;System;Testing;trafficking;uptake;Work;X-Ray Crystallography

PROJECT_TITLE: Structure and function of MCE systems in bacteria

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: This project aims to understand the properties and function of a novel population of specialized cells within the thymus that are derived from cells that previously expressed Aire, a gene that is important in the prevention of autoimmunity. These post-Aire-expressing cells have unique features to that suggest they may further support maturation of T cells and induction of other important regulatory T cells. The proposed studies will define the important characteristics of these cells, how these cells develop, and how they may influence T cell development. The results of these studies will allow us to better understand how these cells may promote immune tolerance to self and prevent autoimmune diseases, such as Type 1 diabetes.

PI_NAMEs: ANDERSON, MARK S (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Ablation;Adopted;Adult;Affect;Antigens;Autoantigens;Autoimmune;Autoimmune Diseases;Autoimmunity;autoreactive T cell;Binding;Biological Response Modifiers;CD80 gene;Cell Compartmentation;Cell Differentiation process;cell type;Cells;Characteristics;Clinical;clinically relevant;Complex;cytokine;Data;Developed Countries;Development;Down-Regulation;Education;Epithelial Cells;falls;Gene Expression Profile;Generations;Genes;Genetic;genetic approach;Growth;Hassall's Corpuscle;Health;Human;Immune system;Immune Tolerance;in vivo;insight;Insulin-Dependent Diabetes Mellitus;Intestines;keratinocyte;Label;Life;Link;Maintenance;Maps;Mediating;MHC Class II Genes;Multiple Sclerosis;Mus;Natural Killer Cells;novel;novel marker;Pathogenicity;Pathway interactions;Peripheral;Play;Polyglandular Autoimmune Syndrome Type I;Population;prevent;Prevention;Process;Property;Receptor Gene;Regulator Genes;Regulatory T-Lymphocyte;Reporter;Role;secondary lymphoid organ;Self Tolerance;Series;Shapes;Signal Transduction;Site;Skin;Stains;Structure of thymic medulla;Syndrome;System;T-Cell Development;T-Lymphocyte;Taste Buds;Testing;Thymic epithelial cell;thymocyte;Thymocyte Development;Thymus Gland;Tissue Microarray;Tissues;tool;transcriptome sequencing

PROJECT_TITLE: Thymic medullary epithelial cell turnover and control of immune tolerance

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: PROVIDENCE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: This COBRE Center will support research focusing on central nervous system function in healthy humans, those with brain disorders and pre-clinical model systems through the activities of the administrative and a research core. The Pilot Project Program will provide resources to early stage investigators and also to established investigators who propose novel lines of inquiry. Overall, the COBRE Center will help facilitate neuroscience research in the Rhode Island community, with collective outcomes that bear upon brain health throughout the United States.

PI_NAMEs: SANES, JEROME N (contact)

PROGRAM_OFFICER_NAME: KOVBASNJUK, OLGA NIKOLAEVNA

PROJECT_TERMS: Applications Grants;Award;Behavior;behavioral phenotyping;Biological Models;Biology;Brain;Brain Diseases;brain health;career;Centers of Research Excellence;Central Nervous System;cluster computing;cognitive enhancement;cohort;Communities;Computational Biology;Core Facility;Country;Data Analyses;design;disease model;Ensure;Environment;Experimental Designs;Faculty;Functional Magnetic Resonance Imaging;Funding;Generations;Goals;Grant;Growth;High Performance Computing;Hospitals;Human;Human Characteristics;Hybrids;Japan;Journals;K-Series Research Career Programs;Leadership;Link;Magnetic Resonance Imaging;member;Mentors;Mission;National Institute of General Medical Sciences;Nervous System Physiology;neuroimaging;Neurons;Neurosciences;Neurosciences Research;novel;Outcome;outreach services;Paper;Peer Review;Performance;Phase;Phase Transition;Pilot Projects;Positioning Attribute;Pre-Clinical Model;Privatization;programs;Publications;Publishing;Records;Research;research facility;Research Infrastructure;Research Institute;Research Methodology;Research Personnel;Research Project Grants;Research Support;Research Technics;Resources;Rhode Island;Rodent;Science;Scientist;Services;success;System;United States;United States Department of Veterans Affairs;United States National Institutes of Health;Universities;Vision;Work;Writing

PROJECT_TITLE: COBRE Center for Central Nervous System Function


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Neurosciences

PROJECT_TERMS: Advisory Committees;Applications Grants;Award;Behavior;behavioral phenotyping;Budgets;career;career development;Centers of Research Excellence;Central Nervous System;cohesion;Collection;Core Facility;data dissemination;data sharing;effectiveness evaluation;Evaluation;Expenditure;Faculty;faculty mentor;Fee-for-Service Plans;Fees;Goals;Grant;Hospitals;Human Resources;Individual;Infrastructure;Journals;Leadership;Magnetic Resonance Imaging;Maintenance;Manuscripts;meetings;Mentors;Mentorship;Mission;Monitor;Nervous System Physiology;neuroimaging;Neurosciences Research;Occupational activity of managing finances;Office of Administrative Management;organizational structure;outreach;Phase;Pilot Projects;Preparation;Principal Investigator;Process;Productivity;programs;Progress Reports;Records;Research;research facility;Research Personnel;Research Project Grants;Resources;Rhode Island;Rodent;Role;Scientist;senior faculty;Series;Service delivery model;Services;Structure;System;Work

PROJECT_TITLE: Administrative Core


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Genetics;Hematology;Infectious Diseases;Sepsis

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Project Narrative  Acute gut barrier dysfunction occurs commonly in patients with critical surgical disorders, leading to the translocation of luminal toxic substances and bacteria to the bloodstream and, in some instances, resulting in multiple organ dysfunction syndrome and death. Effective therapies to preserve the gut barrier integrity are limited, because of poorly understood mechanisms underlying gut barrier dysfunction in various critical surgical conditions. Studies proposed this project will identify the roles and mechanisms of novel extracellular vesicle small noncoding vault RNAs (vtRNAs) in the control of gut barrier function under various critical surgical conditions and will create a fundamental basis for development of new therapies to protect the gut barrier in patients with critical surgical illnesses.

PI_NAMEs: WANG, JIAN-YING  (contact)

PROGRAM_OFFICER_NAME: SENGER, STEFANIA

PROJECT_TERMS: Acute;Affect;Apoptosis;Attention;Autophagocytosis;Bacteria;Biogenesis;Biological Markers;Blood;Blood Circulation;cecal ligation puncture;cell type;Cells;Cessation of life;clinically relevant;conditioning;Critical Illness;Data;Defect;design;Deterioration;Development;Disease;Distant;Drug resistance;effective therapy;Enterocytes;Environment;Epithelial Cells;Epithelium;Eukaryota;Exhibits;Exons;Exposure to;extracellular vesicles;Functional disorder;gastrointestinal epithelium;Genetic Transcription;Goals;H19 gene;heat injury;Homeostasis;Host Defense;Human;human disease;HuR protein;Impairment;In Vitro;in vivo;Inflammatory Bowel Diseases;inhibition of autophagy;intestinal barrier;intestinal epithelium;Intestinal Mucosa;Intestinal permeability;Intestinal Secretions;Ischemia;Link;microbiome;MicroRNAs;Mucous Membrane;multidisciplinary;Multiple Organ Failure;Mus;novel;novel therapeutics;operation;Operative Surgical Procedures;Pathogenesis;Patients;Permeability;Play;Poison;preservation;Regulation;response;RNA;RNA-Binding Proteins;Role;Sepsis;septic;Series;Serum;Shock;Sorting;Stream;Stress;targeted treatment;Testing;Tight Junctions;Tissues;Transcript;Trauma;Untranslated RNA;vesicular release;Virus Replication;Work

PROJECT_TITLE: Surgical Studies of Gut Permeability

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Heart Disease;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Low-income individuals, especially those who are racial minorities, in the US have a disproportionately higher burden of cardiovascular disease, and also have lower rates of health insurance coverage. This study aims to understand whether health insurance coverage for low-income individuals is associated with improvements in access to inpatient and outpatient cardiovascular care, improvements in racial disparities in care access, as well as care after discharge from a cardiovascular hospitalization. The findings of this study will help understand the mechanisms by which recent expansion of Medicaid under the Affordable Care Act was associated with improved cardiovascular mortality, as well as inform future health policies seeking to improve cardiovascular outcomes.

PI_NAMEs: KHATANA, SAMEED AHMED MUSTAFA (contact)

PROGRAM_OFFICER_NAME: REDMOND, NICOLE

PROJECT_TERMS: Acute;Acute myocardial infarction;Adherence;administrative database;adverse outcome;Advisory Committees;Affect;Affordable Care Act;Ambulatory Care;Behavior;behavior influence;Black Populations;Black race;Cardiology;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular health;cardiovascular risk factor;Cardiovascular system;career;Caring;Cessation of life;Chronic;Chronic Care;Cohort Studies;court;Data;Data Set;Databases;Death Rate;Disparity;econometrics;Eligibility Determination;Event;experience;Face;Federal Government;Funding;Future;General Population;Goals;Health;health care availability;health care disparity;health difference;Health Insurance;Health Personnel;Health Policy;health seeking behavior;Health Services Accessibility;Health Status;hospital readmission;Hospitalization;hospitalization rates;Improve Access;improved;Individual;inpatient service;Inpatients;Insurance;Insurance Coverage;Interview;Low income;Low Income Population;Medicaid;Medicaid eligibility;Medical;Medicine;Mentorship;Methodology;Morbidity - disease rate;mortality;Not Hispanic or Latino;Outcome;Outcomes Research;Outpatients;Patient Discharge;Patient-Focused Outcomes;Patients;Policy Maker;Policy Research;Primary Prevention;prospective;Public Health;Publishing;Qualitative Methods;Qualitative Research;Quality of life;racial disparity;racial minority;racial population;Research;Research Methodology;Research Personnel;Risk Factors;Secondary Prevention;Site;Stroke;Structure;Techniques;Time;Training;Uninsured;United States;Work

PROJECT_TITLE: Association of Health Insurance with Access to Cardiovascular Care

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(MA)]


NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Infertility;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Urologic Diseases

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE We will study the cellular and molecular mechanisms that permit a population of stem cells in the vertebrate testis to produce billions of sperm over the lifespan of an individual male. The results of our study will be relevant to our understanding of male infertility, and may direct efforts to culture stem cells in the dish to generate sperm.

PI_NAMEs: GAGNON, JAMES ALAN (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Adolescent;Adult;aged;Animals;Atlases;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;comparative;CRISPR/Cas technology;Development;Gene Expression;Gene Expression Profiling;germline stem cells;Gonadal structure;high resolution imaging;Homeostasis;Human;Individual;Infertility;life span;male;Male Infertility;Methods;Molecular;Mutagenesis;Mutagens;Organ;Phenotype;Phylogenetic Analysis;Population;Process;Regulator Genes;Sampling;self-renewal;single-cell RNA sequencing;sperm cell;stem cell genes;stem cell homeostasis;stem cell population;stem cells;Structure of primordial sex cell;teleost;Testis;Tissues;Trees;Vertebrates;Zebrafish

PROJECT_TITLE: Cellular and molecular mechanisms of vertebrate testis homeostasis

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


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Biomedical Imaging;Building Research Capacity at Institutions with Limited NIH Funding;Data Science;Networking and Information Technology R&D (NITRD);Neurosciences

PI_NAMEs: SHEINBERG, DAVID L (contact)

PROJECT_TERMS: Acceleration;analysis pipeline;analytical tool;Area;Behavior;Behavioral;behavioral phenotyping;Brain;brain research;Businesses;Centers of Research Excellence;Central Nervous System;Clinical;Collaborations;Communities;community involvement;Complex;complex data;computer infrastructure;computerized data processing;computing resources;Consultations;Data;data acquisition;data analysis pipeline;Data Collection;data management;data quality;data repository;Data Set;data sharing;Data Sources;Database Management Systems;Dedications;design;Development;Devices;Diffusion;Diffusion Magnetic Resonance Imaging;Educational workshop;Electroencephalography;Ensure;Environment;Equipment;experimental study;fabrication;Fees;forging;Functional Magnetic Resonance Imaging;Galvanic Skin Response;Goals;Head;High Performance Computing;Image;Individual;Information Dissemination;Infrastructure;Internet;Knowledge;Leadership;Magnetic Resonance Imaging;Maintenance;meetings;Methods;Modeling;Modernization;multimodal neuroimaging;Names;Nervous System Physiology;neuroimaging;Neurosciences;Neurosciences Research;noninvasive brain stimulation;Phase;Play;Procedures;Process;programs;Protocols documentation;quality assurance;Research;Research Activity;research facility;Research Infrastructure;Research Personnel;Research Project Grants;Research Project Summaries;Research Support;Resource Sharing;Resources;Rest;Rhode Island;Rodent;Role;Running;Science;Specific qualifier value;Structure;success;System;Techniques;Technology;Testing;tool;Training;transcranial direct current stimulation;Transcranial magnetic stimulation;visual tracking;Visualization;Work

PROJECT_TITLE: Behavior and Neurodata Core


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Climate-Related Exposures and Conditions;Clinical Research;Digestive Diseases;Endocrine Disruptors;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Liver Disease;Mental Health;Neurosciences;Pediatric;Prevention

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative This investigation will assess concurrent and long-term associations of pesticide exposures with systemic and liver inflammatory markers, and cognitive performance as part of a 12-year follow-up of the ESPINA study, a cohort of children living in agricultural communities in Ecuador. The proposed work will be the first investigation to assess, contrast and account for effects of both insecticides and fungicides (measured in urine) on children's health. Findings from this research will advance the current field of environmental health and inform future risk assessments and disease prevention programs in children and adolescents.

PI_NAMEs: SUAREZ, JOSE RICARDO (contact)

PROGRAM_OFFICER_NAME: GRAY, KIMBERLY A

PROJECT_TERMS: Acetylcholinesterase;Adolescence;Adolescent;Affect;Age;agricultural community;agricultural pesticide;Agriculture;Americas;anti-fungal agents;Azoles;biobank;Biological Markers;Blood;CCL2 gene;Child;Child Development;Child Health;Cholinesterase Inhibitors;clinical practice;Cognition;Cognitive;cognitive performance;cohort;County;Cytochrome P450;Cytokeratin 18;Data Collection;Development;developmental toxicity;Disease;disorder prevention;Drug Metabolic Detoxication;Ecuador;Environmental Health;Enzymes;epidemiology study;Epigenetic Process;experimental study;exposure pathway;Exposure to;Fatty Liver;Flowers;follow-up;Food;Free Radicals;fruits and vegetables;Funding;fungicide;Future;Gender;Hair;Health;Hepatotoxicity;Human;Impairment;In Vitro;individuals with autism spectrum disorder;Inflammation;inflammatory marker;inhibitor;Insecticides;Interleukin-6;Investigation;Link;Liver;liver inflammation;Measurement;Measures;Mediating;Mental Health;Methods;Microtubules;monocyte;National Institute of Environmental Health Sciences;Nerve Degeneration;neurobehavior;neurobehavioral;Neurocognition;Neurocognitive;Neurocognitive Deficit;neuroinflammation;Neurons;neurotoxic;novel;Organophosphates;Outcome;Participant;Patients;Performance;pesticide exposure;Pesticides;Pharmaceutical Preparations;Physiological;Plasma;Population;prenatal exposure;Prevention program;Process;Production;prospective;Prospective Studies;prospective test;pyrethroid;Quinones;Recurrence;Research;Risk Assessment;Safety;Sales;Saliva;Sampling;Serum;Structure;study population;Technology;Testing;Time;TNF gene;Toxic effect;Transaminases;United States National Institutes of Health;urinary;Urine;Vascular Endothelium;Work;young adult

PROJECT_TITLE: The 2020 ESPINA study follow-up Exam: Fungicides, Insecticides, Inflammation and Child Development

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


NIH_SPENDING_CATS: Clinical Research;Hematology;Immunotherapy;Infectious Diseases;Physical Injury - Accidents and Adverse Effects;Sepsis

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE Rather than acute mortality, a significant proportion of severe trauma and sepsis patients develop chronic critical illness (CCI), primarily characterized by recurrent infections, a failure to physically rehabilitate and dismal long- term outcomes. The overarching goal of our laboratory’s research program is to define distinct immunologic endotypes after severe injury or sepsis, to determine their role in the chronic inflammation, immunosuppression and muscle wasting, and to delineate their interactions, such that therapeutic interventions may be identified.

PI_NAMEs: BRAKENRIDGE, SCOTT CHARLES (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Acute;Age;Area;Catabolism;Chronic;Clinical;clinical development;clinical phenotype;clinically relevant;Critical Illness;cytokine release syndrome;design;Ethnic Origin;Event;Failure;Functional disorder;Genomics;Goals;Health care facility;Heterogeneity;Homeostasis;Hospitals;Immune;Immune response;Immunity;Immunologics;Immunosuppression;indexing;Infection;Inflammation;Inflammatory;Innate Immune Response;innovation;Intensive Care Units;Laboratory Research;Mediating;Mediator;microbial products;mortality;Multiple Organ Failure;Muscle;Muscular Atrophy;novel;Organ;organ injury;Outcome;Pathway interactions;Patients;Phenotype;Production;programs;Race;Recurrence;recurrent infection;Refractory;Research;Resources;Resuscitation;Role;secondary infection;Sepsis;septic patients;severe injury;sex;Source;Supportive care;Survivors;Syndrome;systemic inflammatory response;Therapeutic Intervention;therapeutically effective;Time;Trauma;Trauma patient;Traumatic injury;Work

PROJECT_TITLE: Immunological Endotyping of Chronic Critical Illness after Severe Trauma or Sepsis

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


PROJECT_TERMS: Award;Budgets;Career Mobility;Centers of Research Excellence;Central Nervous System;Clinical Research;Communities;Core Facility;design;Direct Costs;Educational process of instructing;Eligibility Determination;Environment;Faculty;Funding;Funding Agency;Goals;Grant;Growth;Mentors;Nervous System Physiology;Neurosciences;Neurosciences Research;novel;Phase;Phase Transition;Pilot Projects;programs;Recording of previous events;recruit;Research;Research Personnel;Research Project Grants;Research Support;Rhode Island;Scientist;service organization;success;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Pilot Projects Program


ORG_CITY: BLACKSBURG

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

PHR: Project Narrative  This proposal aims to develop catalytic asymmetric transformations using organoboron compounds. The proposed studies will explore novel reactivities of organoboron compounds to address the challenges in asymmetric synthesis. It is anticipated that the studies will allow for the access to enantioenriched molecules that are valuable for organic synthesis, and relevant to medicinal chemistry and drug discovery.

PI_NAMEs: CHEN, MING  (contact)

PROJECT_TERMS: Address;Agrochemicals;Anions;Area;Biology;Boron;Carbon;Chemicals;chiral molecule;Collaborations;computational chemistry;design;Development;drug discovery;Drug Industry;Generations;Health;Human;innovation;materials science;metal complex;Methods;novel;Organic Synthesis;Pharmaceutical Chemistry;Process;programs;Property;Reaction;Research;three dimensional structure

PROJECT_TITLE: Asymmetric Synthesis via Organoboron Compounds


ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE COUNTY

PHR: Project Narrative In the proposed research, we will develop physiologically relevant yet easy-to-use liver modeling technologies; meanwhile, new insights regarding ECM-cell metabolism interactions will be generated for future therapy developments targeting fibrosis.

PI_NAMEs: CHEN, CHENGPENG  (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TERMS: 3-Dimensional;5'-AMP-activated protein kinase;Architecture;cell type;Cellular Metabolic Process;cost;Dedications;Development;drug development;Extracellular Matrix;fabrication;Fibrosis;Future;Hepatic;Homeostasis;human subject;Impairment;innovative technologies;insight;Integrins;Laboratories;Literature;Liver;liver metabolism;Logic;Maintenance;Metabolic;metabolic abnormality assessment;Microfluidics;Modeling;novel therapeutics;operation;Pharmacologic Substance;Physiological;Property;Proteins;Reporting;Research;Risk;Role;screening;Structure;success;Technology;Testing;therapy development;Time;Tissue Model;Work

PROJECT_TITLE: A physiological and translational liver model to study the metabolism-modulating roles of extracellular matrix microstructures


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Epilepsy;Genetics;Neurodegenerative;Neurosciences

ORG_DEPT: NEUROLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Non-lesional focal epilepsy (NLFE) is a common and difficult to treat condition that consists of recurrent seizures arising from a brain region with no apparent abnormality on standard clinical MRI. Recently, we identified brain-specific somatic variants in the gene SLC35A2 as a cause of NLFE. We propose to clarify clinical phenotypes associated with these mutations, further define the range of somatic genetic mutations in this and other genes, use advanced imaging to detect subtle abnormalities preoperatively, and determine the spatial patterns of histopathologic and electrophysiologic alterations in NLFE.

PI_NAMEs: CRINO, PETER B;HEINZEN, ERIN L;WINAWER, MELODIE ROSE (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Age;Alleles;Area;Biological Markers;Biology;Biopsy;Biopsy Specimen;BRAF gene;Brain;Brain imaging;Brain region;brain tissue;Caring;Cerebral cortex;Characteristics;Childhood;Clinical;clinical phenotype;cohort;Cortical Dysplasia;Detection;Development;disease-causing mutation;DNA Sequence Alteration;DNA sequencing;Electroencephalography;Electrophysiology (science);Epilepsy;Evaluation;Excision;Exhibits;exome sequencing;Focal Seizure;FRAP1 gene;Frequencies;Functional disorder;gene discovery;Gene Frequency;Genes;Genetic;Genetic Predisposition to Disease;genetic variant;Genotype;Histopathology;Image;improved;Individual;Investigation;Lesion;Link;Magnetic Resonance Imaging;malformation;Medical;Mutation;novel;Operative Surgical Procedures;Outcome;Partial Epilepsies;Pathogenicity;Pathologic;Pathology;Pattern;Phenotype;Positioning Attribute;Procedures;prospective;radiological imaging;Recurrence;Resected;Resolution;Role;Sample Size;Sampling;Seizures;Signal Transduction;Site;Somatic Mutation;Source;structural imaging;Structure;success;surgery outcome;Techniques;Time;Tissues;UDP-galactose transporter;Variant

PROJECT_TITLE: Somatic Mutation in Intractable Focal Epilepsy


ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Cellular metabolic enzymes are critical for survival and are also aberrant in many human pathologies including cancer, diabetes, and genetic diseases. One major pathway linked to several diseases is a complex pathway called autophagy. This proposal will seek to understand the enzymes involved in autophagy and other metabolic pathways using chemical probes and structural biology.

PI_NAMEs: LAZARUS, MICHAEL BLOCK (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Alzheimer's Disease;Autophagocytosis;Binding;Biology;Cells;Chemicals;Collaborations;Communities;Complex;Crystallography;Degradation Pathway;Diabetes Mellitus;Disease;disease model;drug discovery;enzyme structure;Enzymes;Family;Family member;Funding;Generations;Genetic Diseases;glutaric acidemia;glycosyltransferase;Goals;Homeostasis;Human Biology;human disease;Human Pathology;Inborn Errors of Metabolism;inhibition of autophagy;inhibitor;Link;Lysine;Malignant Neoplasms;Metabolic;Metabolic Diseases;Metabolic Pathway;Molecular;multidisciplinary;nanomolar;Nerve Degeneration;O-GlcNAc transferase;Pathway interactions;Patients;Pharmaceutical Chemistry;Phosphotransferases;Positioning Attribute;programs;protein degradation;proteostasis;Quality Control;Research;Resolution;Role;Schizophrenia;sensor;Starvation;structural biology;Structure;synergism;therapeutic target;Vision

PROJECT_TITLE: Chemical and Structural Approaches to Study Energy Homeostasis Pathways in Cancer and Metabolic disorders


ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition in which a somatic mutation that is associated with blood cancers is detectable in the peripheral blood. We propose to examine the biology of individual mutations, to interrogate how CHIP progresses to malignancy, and to investigate how mutant blood cells might alter solid tumor development and response to therapy.

PI_NAMEs: EBERT, BENJAMIN LEVINE (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: addiction;age related;Biological;Biology;Blood;Blood Cells;cancer cell;Cells;Clinical;Development;DNMT3a;Genes;Genetic;Genetic study;genetic variant;Growth;Hematologic Neoplasms;Hematopoiesis;Hematopoietic Neoplasms;Immune response;Immunotherapy;Individual;Infiltration;Macrophage;Malignant - descriptor;Malignant Neoplasms;mutant;Mutate;Mutation;Myeloproliferative disease;peripheral blood;progression risk;response;Risk;Role;Solid Neoplasm;Somatic Mutation;therapeutic target;treatment response;tumor;Tumor Biology

PROJECT_TITLE: The role of clonal hematopoiesis in the development and therapy of myeloid malignancies


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biodefense and Related Countermeasures;Brain Disorders;Clinical Research;Dementia;Emerging Infectious Diseases;Frontotemporal Dementia (FTD);Infectious Diseases;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease;Prevention;Rare Diseases;Transmissible Spongiform Encephalopathy (TSE)

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Using an ultrasensitive RT-QuIC/PMCA assays, our recent study has indicated that skin samples of patients with Creutzfeldt-Jakob disease or Parkinson's disease, neurodegenerative diseases associated with the deposition of misfolded protein aggregates (PrPSc) or α-Synuclein, contains detectable PrPSc or α-Synuclein. The aim of the current proposal is to extend our preliminary finding to test a new hypothesis that skin tissues of Alzheimer's disease (AD), the most common neurodegenerative disease, contain the misfolded tau that can be a biomarker for diagnosing, characterizing and predicting outcome of AD.

PI_NAMEs: CHEN, SHU G.;KRAUS, ALLISON L (contact);WANG, ZERUI ;XU, BIN

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: Age;alpha synuclein;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease related dementia;Amyloid beta-Protein;Animal Model;Animals;Area;Autopsy;Biochemical;Biological Assay;Biological Markers;biomarker identification;Biopsy Specimen;Blinded;Brain;Brain imaging;Brain Injuries;brain tissue;Cadaver;Cerebrospinal Fluid;Clinical;Clinical Trials;corticobasal degeneration;Creutzfeldt-Jakob Syndrome;Dementia;Deposition;Detection;Development;Diagnosis;diagnostic biomarker;Diagnostic tests;Differential Diagnosis;Disease;Disease Progression;early detection biomarkers;Early Diagnosis;Exhibits;Goals;Histologic;Human;Hypersensitivity skin testing;Immunoassay;Individual;Lewy Body Dementia;Measures;misfolded protein;mouse model;Mutation;neurobehavioral;Neurodegenerative Disorders;neuropathology;novel marker;outcome prediction;Outcome Study;Parkinson Disease;Pathologic;Patients;Peripheral;Pick Disease of the Brain;potential biomarker;pre-clinical;predict clinical outcome;Prion Diseases;prion-like;Prions;Progressive Supranuclear Palsy;protein aggregation;Protein Isoforms;protein misfolding cyclic amplification;PrP;PrPSc Proteins;Radioactivity;Recombinants;Sampling;Severity of illness;sex;Site;Skin;skin biopsy;Skin Tissue;Specimen;Spinal Puncture;tau aggregation;tau Proteins;Tauopathies;Technology;Testing;therapeutic evaluation;Time;Treatment Efficacy

PROJECT_TITLE: Skin biomarkers for diagnosing and characterizing AD and ADRD

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Tickborne Diseases;Vector-Borne Diseases

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: Project Narrative The goal of this study is to demonstrate the natural course of SFTSV infection and reassortment for fitness, immunogenicity, transmissibility, and pathogenesis in in vitro and in vivo animal models and H. longicornis ticks, ultimately bridging basic research to clinical application.

PI_NAMEs: JUNG, JAE U (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: 4 year old;Affect;Age;age related;aged;Animal Model;Animals;Antigenic Variation;Arboviruses;Asia;Attenuated Live Virus Vaccine;Basic Science;Biological Assay;Blood;Cell Culture Techniques;Cells;Characteristics;climate change;Clinical;clinical application;clinical diagnosis;CNR1 gene;co-infection;Communicable Diseases;Coxiella;Dangerousness;Death Rate;Disease;DNA Vaccines;egg;Emergency Situation;Epidemic;Far East;Fatality rate;feeding;Female;Ferrets;Fever;fitness;Future;Genes;Genetic;Genetic Processes;Genetic Recombination;Genome;Genotype;Glycoproteins;Goals;Haemaphysalis longicornis;Heartland virus;Human;IFNAR1 gene;Immunocompetent;immunogenicity;In Vitro;in vivo;Infection;insight;Interferons;Larva;Mammals;Mediating;Methods;Midgut;Modeling;mortality;mouse model;Mus;Nature;neutralizing antibody;novel;Nymph;older patient;Orthobunyavirus;outbreak concern;Ovary;pathogen;Pathogenesis;pathogenic virus;Pathogenicity;Patients;Phenotype;reverse genetics;Risk Factors;RNA;RNA Viruses;Role;Salivary;Salivary Glands;Severe Fever with Thrombocytopenia Syndrome Virus;symbiont;Symptoms;Syndrome;System;Testing;Thrombocytopenia;tick feeding;tick-borne;tick-borne virus;Ticks;Time;tool;transmission process;vector;viral fitness;Viral Pathogenesis;viral transmission;Virus;Virus Diseases;virus testing;Virus-like particle

PROJECT_TITLE: Reassortment of Bunyavirus in ticks and animal models


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Social Determinants of Health;Substance Misuse

ORG_CITY: LOWELL

ORG_NAME: UNIVERSITY OF MASSACHUSETTS LOWELL

PHR: Social and behavioral determinants of MOUD utilization and opioid overdose In the US, over 192 people die each day due to opioid overdose (OOD), the leading cause of accidental death among adults. Veterans are especially vulnerable to OOD, experiencing rates double those of non-Veterans, due to their higher prevalence of opioid use disorder (OUD). Medication treatment for OUD (MOUD) is the gold standard treatment for opioid use disorder (OUD). However, in the Veterans Health Administration of the Department of Veterans Affairs (VA), access to MOUD care is lacking. Compounding poor access, many patients who receive MOUD discontinue within 1 year, an indicator of suboptimal treatment retention. The overarching goal of this proposal is to understand social and behavioral determinants of health, biological variables, clinical settings and clinical factors that impact MOUD access and outcomes and to develop predictive models for MOUD outcomes.

PI_NAMEs: LI, WENJUN ;SMELSON, DAVID A;YU, HONG  (contact)

PROGRAM_OFFICER_NAME: MARTIN, LINDSEY ANN

PROJECT_TERMS: Accidents;Address;Adult;Age;allostatic load;Behavioral;behavioral health;Biological;Black American;Buprenorphine;Caring;Cessation of life;Clinical;cohort;Communities;coping;Data;deep learning model;demographics;Dose;electronic health information;Electronic Health Record;electronic structure;Ensure;ethnic minority;Ethnic Origin;experience;Exposure to;Financial Hardship;Food;food insecurity;General Population;Goals;Health;health determinants;health record;High Prevalence;Hospitals;Housing;illicit drug use;improved;Individual;innovation;intersectionality;Legal;Machine Learning;Major Depressive Disorder;male health;Marital Status;Mental disorders;Methadone;mindfulness;Modeling;Naltrexone;Natural Extract;Natural Language Processing;Occupations;Opioid;opioid overdose;opioid use disorder;Outcome;Overdose;patient population;Patients;Persons;Pharmaceutical Preparations;Population;Positioning Attribute;predictive modeling;primary care setting;prospective;Race;racial minority;Regression Analysis;Research;Resources;Risk;sex;social;social health determinants;Social Work;standard care;Stress;Structure;structured data;substance use;System;theories;Time;Transportation;United States Department of Veterans Affairs;unstructured data;Veterans;Veterans Health Administration;Violence;Washington;Woman;Work

STUDY_SECTION: LHB

STUDY_SECTION_NAME: Lifestyle and Health Behaviors Study Section[LHB]


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;HIV/AIDS;Infectious Diseases;Prevention;Sexually Transmitted Infections

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an urgent global health threat and the prevalence is highest in the Western Pacific Region. The proposed study will identify risk factors for AMR, measure treatment outcomes of pharyngeal infections, and investigate the genomic epidemiology of AMR in N. gonorrhoeae among men who have sex with men in an HIV pre-exposure prophylaxis (PrEP) program in Vietnam. By contributing new knowledge about AMR in N. gonorrhoeae and providing crucial information from a population at high risk for AMR, this proposal will help guide public health efforts aimed at mitigating the spread of drug-resistant gonorrhea.

PI_NAMEs: ADAMSON, PAUL C (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Address;Affect;Aftercare;Anatomy;Antibiotic susceptibility;Antibiotic Therapy;Antibiotics;antimicrobial;Antimicrobial Resistance;Asia;Azithromycin;Bacteria;Behavioral;Bioinformatics;Biometry;burden of illness;career;career development;Cefixime;Ceftriaxone;Cephalosporin Resistance;Cephalosporins;Clinical Data;Clinical Microbiology;Clinical Trials;cohort;Collaborations;Communicable Diseases;Consumption;Data;Detection;Diagnosis;Diagnostic;DNA Sequence Alteration;drug-resistant gonorrhea;Elements;Epidemiology;epidemiology study;Etiology;Europe;experience;follow-up;Frequencies;Future;Genetic;Genetic Markers;genome sequencing;genomic epidemiology;Genomics;Genotype;global health;global health emergency;Goals;Gonorrhea;high risk;HIV;improved;Infection;Injectable;International;Intervention;Knowledge;Link;low and middle-income countries;Measures;Medical;men;men who have sex with men;Mentored Research Scientist Development Award;Mentors;Mentorship;Molecular Epidemiology;Neisseria;Neisseria gonorrhoeae;Oropharyngeal;pharyngeal gonorrhea;Pharyngeal structure;Phenotype;Physicians;Population;pre-exposure prophylaxis;Predisposition;Prevalence;Prevention Research;priority pathogen;programs;Public Health;Recommendation;Rectum;Reporting;Research;Research Infrastructure;Research Personnel;research study;Resistance;Resistance development;Resistance to infection;Risk Factors;Sexually Transmitted Diseases;study population;Testing;Training;Treatment Failure;Treatment outcome;United Kingdom;United Nations;Universities;Urethra;Vietnam;whole genome;World Health Organization

PROJECT_TITLE: Antimicrobial resistance in Neisseria gonorrhoeae among men on PrEP in Vietnam

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-ICP-L(57)R]


ORG_CITY: BOSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative Newly emerging and re-emerging infectious diseases represent continuing threats to human health, both nationally and globally. To improve our ability to diagnose, treat and prevent these potentially pandemic pathogens, we must understand their biology and pathogenic mechanisms in order to develop the tools we need. The mission of the NEIDL is to conduct this basic and translational research in a safe and secure environment, and through our research and collaborations accelerate the research and development of diagnostics, therapeutics, and vaccines for known and still to be identified emerging microbial threats.

PI_NAMEs: SULLIVAN, NANCY JEAN (contact)

PROGRAM_OFFICER_NAME: DIAZ SAN SEGUNDO, FAYNA C

PROJECT_TERMS: Acceleration;Advanced Development;Animal Model;Animals;Area;Attention;Basic Science;biocontainment facility;biodefense;Biology;biosecurity;Boston;Categories;Clinical Research;Collaborations;Communities;Comparative Study;Complement;Containment;Development;Diagnosis;Diagnostic;diagnostic development;Diagnostic tests;Discipline;Emergency Situation;Emerging Communicable Diseases;emerging pathogen;Engineering;Environment;Environmental Health;Event;experience;Faculty;Faculty Recruitment;flexibility;Goals;Health;Human;human disease;Human Resources;improved;Infectious Diseases Research;Information Technology;innovation;insight;interest;International;Investigation;Laboratories;Medical;Medical center;medical schools;Methodology;microbial;Mission;Modeling;new technology;next generation;operation;pathogen;Pathogenesis;Pathogenicity;pathogens of pandemic potential;Physiological;pre-clinical research;prevent;Process;programs;Public Health;Public Health Schools;recruit;Reporting;Research;research and development;research facility;Research Personnel;Research Support;response;Safety;Science;Scientist;Secure;Security;Services;skills;Strategic Planning;Teaching Hospitals;Therapeutic;tool;Training;Training and Education;Translational Research;United States;Universities;vaccine evaluation;Vaccines;Veterinary Pathology

PROJECT_TITLE: National Emerging Infectious Diseases Laboratories Operations


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

PI_NAMEs: CORLEY, RONALD B (contact)

PROJECT_TERMS: biocontainment facility;biodefense;biosafety level 4 facility;biosecurity;Collaborations;Communication;Communities;Coordination and Collaboration;cost;data sharing;Development;Diagnostic;Emerging Communicable Diseases;Ensure;Faculty;Goals;Infectious Diseases Research;Infrastructure;Leadership;member;Mission;National Institute of Allergy and Infectious Disease;novel therapeutics;operation;organizational structure;pathogen;Pathogenesis;Process;Productivity;Recovery;Research;Research Support;Resources;Role;Services;Structure;Training Activity;Universities;Vaccines

PROJECT_TITLE: Administration


PI_NAMEs: RUSK, SCOTT  (contact)

PROJECT_TERMS: Address;Aging;Area;biocontainment facility;Boston;Communicable Diseases;Communication;Communities;community engagement;Community Outreach;Community Relations;computing resources;Containment;cost effective;COVID-19 pandemic;Dedications;Development;Documentation;Education;Educational Status;Effectiveness;Emerging Communicable Diseases;Environment;Future;Goals;Government;Hand;Health;Human Resources;improved;Infectious Diseases Research;Information Services;Information Systems;Information Technology;Infrastructure;instrumentation;Laboratories;laboratory experience;Lead;Leadership;Maintenance;Medical;member;Mission;mobile application;operation;Parents;Performance;Persons;Procedures;programs;repaired;Research;Research Personnel;Resources;response;Risk;Risk Assessment;Role;Safety;Schools;Science;Security;Services;Students;System;Tablets;Technology;Testing;Training;Training and Education;Trust

PROJECT_TITLE: Core 1: FACILITIES MAINTENANCE AND OPERATION


NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Genetics;Immunotherapy;Liver Cancer;Liver Disease;Orphan Drug;Precision Medicine;Rare Diseases

PHR: NARRATIVE Despite increasing relevance and incidence rates, drugs that effectively target HCC remain elusive. In this project, we advance a multidisciplinary drug development platform that utilizes precision mouse models, tumor 3D organoids, and a proprietary library of small molecule inhibitors as a launching point to uncover novel biological targets, mechanisms, and a new class of lead compounds for precision-based therapeutics in HCC.

PI_NAMEs: DAR, ARVIN ;GUCCIONE, ERNESTO  (contact);LUJAMBIO, AMAIA

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: 3-Dimensional;Animals;BAY 54-9085;beta catenin;Binding;biobank;Biological;Biological Assay;Biology;Cancer Etiology;carcinogenesis;Cells;Cessation of life;chemical genetics;Chemicals;Chromatin;Clinical;comparative efficacy;Complex;cost;Critical Pathways;CTNNB1 gene;Data;Death Rate;Dependence;Development;Dimensions;Disease;Drug Design;drug development;drug discovery;Drug Targeting;Ensure;Enzymes;Epigenetic Process;epigenomics;Failure;FDA approved;gene repression;Genetic;Genetic Screening;Genetic Transcription;Genetically Engineered Mouse;Genomics;Genotype;Goals;Growth;Heterogeneity;Histones;Human;Immune checkpoint inhibitor;Immune system;Immunotherapy;improved;Incidence;insight;kinase inhibitor;Lead;liver cancer model;Malignant neoplasm of liver;Malignant Neoplasms;Modeling;mortality;mouse model;multidisciplinary;Mus;mutant;Mutation;Nature;new therapeutic target;novel;Oncogenic;Organoids;patient derived xenograft model;patient population;patient stratification;Patients;personalized therapeutic;Pharmaceutical Preparations;Phenotype;Phosphotransferases;Pre-Clinical Model;Precision therapeutics;preference;Primary carcinoma of the liver cells;programmed cell death protein 1;Proteomics;Publishing;Regulation;Research;Sampling;Signal Pathway;Signal Transduction;small molecule;small molecule inhibitor;small molecule libraries;standard of care;Stratification;Structure-Activity Relationship;synergism;targeted treatment;Testing;Therapeutic;tool;Toxic effect;tumor;tumor microenvironment;Validation;Xenograft procedure

PROJECT_TITLE: AN INTEGRATED PLATFORM FOR NOVEL PERSONALIZED LIVER CANCER THERAPEUTICS

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: NARRATIVE This program will provide research training for individuals who will make important contributions to our understanding of how inflammation and fibrosis contribute to rheumatic diseases such as scleroderma and systemic lupus erythematosus. We have expanded the program to include research in additional rheumatic diseases and into different fields of research including the microbiome, cellular therapies and regenerative approaches to rheumatic diseases. Our trainee pool has expanded significantly over the last 15 years, both in number and quality, allowing us to further expand the opportunities in research training for enhancing rigor and research ethics and integrity.

PI_NAMEs: GILKESON, GARY S (contact)

PROGRAM_OFFICER_NAME: VINCENT, ISAAH S

PROJECT_TITLE: Training Grant in Inflammatory and Fibrosing Diseases


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Prevention;Social Determinants of Health

PI_NAMEs: NEE, KELLY A (contact)

PROJECT_TERMS: Academy;Accountability;arm;Biological;biosecurity;Boston;Collaborations;Computer Security;Data Security;design;Development;Elements;Emergency Situation;Emerging Communicable Diseases;Ensure;Environment;Environmental Health;Equipment and supply inventories;Event;Exercise;Fire - disasters;Firearms;first responder;Grant;Hazardous Substances;Hour;Human Resources;Infectious Diseases Research;Information Technology;Institution;Laboratories;Law Enforcement;Leadership;Licensing;Location;Maintenance;Massachusetts;Medical;Medical emergency;member;Mission;operation;Pathogenicity;Personnel Management;Police;Police officer;Policies;Preparation;prevent;Process;programs;prospective;Public Health;recruit;Regulation;Research;Risk Assessment;Safety;screening;Secure;Security;Services;Specialist;Statutes and Laws;System;Theft;tool;Training;Training Programs;Transportation;Universities;virology;Work;working group

PROJECT_TITLE: Core 2: BioSecurity


PI_NAMEs: TUOHEY, KEVIN MICHAEL (contact)

PROJECT_TERMS: Address;Advisory Committees;Area;biosafety level 4 facility;Boston;Budgets;Centers for Disease Control and Prevention (U.S.);Certification;chemical safety;Chemicals;Collaborations;Competence;Contract Services;Core Facility;Decontamination;Development;Disease Surveillance;Emergency response;Emergency Situation;Emerging Communicable Diseases;Employment;Ensure;Environmental Health;Equipment;Equipment and supply inventories;Exercise;exercise program;follow-up;hazard;Health;Human Resources;Hygiene;Individual;Infectious Diseases Research;Institution;institutional biosafety committee;Investigation;Laboratories;Leadership;Maintenance;Medical;Medical Surveillance;Monitor;Occupational Health;Occupational Medicine;operation;Principal Investigator;Process;Professional Organizations;programs;Public Health;Radiation;Readiness;Records;Regulation;Regulatory Affairs;Reporting;Research;Resources;response;Role;Safety;Services;System;Testing;Training;Universities;Work

PROJECT_TITLE: CORE 3: Environmental Health and Biosafety Regulations and Requirements


ORG_DEPT: PHYSICS

PHR: Project Narrative: This project concerns the development of a nanopore-based single-molecule protein reader, building on promising initial results showing single-amino acid sensitivity at the single-molecule level at extremely high fidelity. We aim to make key developments turning this concept into a technology with direct applications in fundamental biology and the clinic.

PI_NAMEs: DEKKER, CEES ;GUNDLACH, JENS  (contact)

PROGRAM_OFFICER_NAME: FUFA, TEMESGEN D

PROJECT_TERMS: Address;Amino Acid Sequence;Amino Acid Substitution;Amino Acids;Binding;Biological;Biology;Charge;Chemicals;Chemistry;Chimeric Proteins;Clinic;Clinical;Clinical Medicine;clinically relevant;Collaborations;comparative;Complex;constriction;cost;Data;Data Analyses;Data Set;Detection;detection limit;Development;Devices;direct application;Discrimination;DNA;DNA sequencing;Electronics;Elements;Engineering;flexibility;Funding;Goals;Head;Health;helicase;Heterogeneity;Human;improved;Individual;interest;Ions;Label;Laboratories;Length;Libraries;Maps;Mass Spectrum Analysis;Measurement;Measures;Messenger RNA;Methodology;Methods;Motivation;multicatalytic endopeptidase complex;Mutation;nanopore;new technology;Nucleotides;Oligonucleotides;Peptide Sequence Determination;Peptides;Point Mutation;polypeptide;Pore Proteins;Positioning Attribute;Post-Translational Protein Processing;Process;progenitor;Property;protein aminoacid sequence;Protein Analysis;Protein Array;Protein Fragment;Proteins;Proteomics;Protocols documentation;Reader;Reading;RNA Splicing;Sampling;Signal Transduction;single molecule;Structure;success;synthetic peptide;Techniques;Technology;technology development;tool;Variant;variant detection;Vestibule;Vision;Work

PROJECT_TITLE: Towards Single-Molecule Protein Sequencing with Nanopores


NIH_SPENDING_CATS: Emerging Infectious Diseases;Infectious Diseases

PROJECT_TERMS: Advanced Development;Agreement;Animal Model;animal rule;Biological;Boston;Communication;Containment;Control Animal;Data;Development;efficacy evaluation;Emerging Communicable Diseases;Evaluation;good laboratory practice;Human Resources;improved;Infectious Diseases Research;Leadership;Maintenance;medical countermeasure;member;Monitor;operation;Participant;pathogen;Policies;Principal Investigator;Procedures;Process;programs;Protocols documentation;quality assurance;Regulation;risk mitigation;Safety;Schedule;System;Testing;Training;United States Food and Drug Administration;Universities;Work

PROJECT_TITLE: Core 4: Regulatory Compliance


PROJECT_TERMS: Accreditation;Address;Anatomy;Animal Experimentation;Animal Model;Animal Technicians;Animals;Autopsy;Basic Science;Biotechnology;Boston;Cells;Clinic;Clinical;Clinical Chemistry;Collaborations;Communities;comparative;Comparative Pathology;Competence;Containment;cost;Development;Diagnostic;Emerging Communicable Diseases;Ensure;Equipment and supply inventories;Faculty;Fees;Fees and Charges;Flow Cytometry;Fostering;frontier;Funding;Future;Goals;high throughput screening;IACUC;Image;Immunology;Individual;Infectious Agent;Infectious Diseases Research;Infrastructure;innovation;Institution;instrumentation;International;Laboratories;Libraries;Light;Link;Maintenance;Methodology;Methods;Microscopy;Monitor;operation;Outcome;pathogen;Pathologist;Pharmacologic Substance;Private Sector;Procedures;programs;Protocols documentation;Reagent;recruit;Regulation;Research;research and development;Research Personnel;Research Project Grants;Research Support;Resources;response;Safety;Sampling;Sampling Studies;Schedule;Science;Scientific Inquiry;Scientist;screening;Services;single cell sequencing;skills;small molecule inhibitor;Specimen;Technical Expertise;Technology;Therapeutic;Time;Tissues;tool;Training;translational research program;Universities;Vaccines;Veterinary Pathology;Viral;viral genomics;virology;Virus;Visual;Work

PROJECT_TITLE: Core 5: Integrated Support Services


ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: PROJECT NARRATIVE Clostridioides difficile infection remains a significant public health problem that has persisted because of failures to develop an efficacious vaccine. Toxins secreted by C. difficile during infection drive disease pathology, subvert the host immune response, and leave patients vulnerable to recurrent infection. In the Oklahoma C. difficile U19 program, a consortium of investigators will undertake three distinct but complementary projects to advance a second generation vaccine candidate and to understand the mechanisms by which C. difficile toxins subvert the host immune response and contribute to vaccine failure.

PI_NAMEs: LANG, MARK L (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Advanced Development;Affect;anti-toxin;Antibodies;Antibody Response;Area;arm;base;Biometry;Cell Compartmentation;Centers of Research Excellence;Clostridioides difficile vaccine;Clostridium difficile;Collaborations;Communicable Diseases;Communities;Complement;design;Development;Disease;Engineering;Enteral;Enteric Nervous System;Equilibrium;experimental study;Faculty;Failure;Funding;Generations;Goals;Human;Humoral Immunities;Immune;Immune Evasion;Immune response;Immune system;Immunity;Infection;innovation;insight;Institution;interest;Investigation;Joints;Knowledge;Mediating;member;Memory B-Lymphocyte;microbial;Nervous System;Oklahoma;Outcome;pathogen;Pathogenesis;pathogenic bacteria;Pathogenicity;Pathology;Patients;Preclinical Testing;Program Description;programs;Public Health;recruit;recurrent infection;Research;Research Personnel;Research Project Grants;Resources;response;Signal Transduction;success;Testing;Toxin;United States National Institutes of Health;Vaccination;vaccination strategy;vaccine candidate;Vaccine Clinical Trial;vaccine evaluation;vaccine failure;vaccine immunogenicity;vaccine response;vaccine strategy;vaccine-induced immunity;Vaccinee;Vaccines;Work

PROJECT_TITLE: Advancing a second generation C. difficile vaccine


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

PROJECT_TERMS: Award;Benchmarking;Clostridioides difficile vaccine;Clostridium difficile;Collaborations;Communication;Coordination and Collaboration;Ensure;enteric pathogen;Fostering;Funding;Generations;Goals;Group Meetings;Growth;Immune response;Institution;meetings;Monitor;multidisciplinary;National Institute of Allergy and Infectious Disease;Office of Administrative Management;Oklahoma;outreach;Pathogenesis;Phase;programs;Progress Reports;Research;Research Personnel;Research Project Grants;Scientist;success;Travel;United States National Institutes of Health;vaccine development

PROJECT_TITLE: Oklahoma C. difficile U19 Administrative Core


NIH_SPENDING_CATS: Atherosclerosis;Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease;Nutrition

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: NARRATIVE The lipid and cholesterol-rich Western diet causes increased blood low-density lipoprotein (LDL) which are pathologically linked to many human diseases, but the underlying mechanisms are poorly understood. This study proposes that native LDL plays a critical role in inducing inflammation by activating inflammatory signaling pathways which will be tested using in vitro biochemical assays and animal models of intestinal inflammation. Findings of this study will lead to developing novel therapies for LDL-linked inflammatory and metabolic disorders by targeting molecules involved in LDL-mediated activation of inflammatory signaling pathways.

PI_NAMEs: ZAKI, HASAN  (contact)

PROGRAM_OFFICER_NAME: SENGER, STEFANIA

PROJECT_TERMS: Anabolism;Animal Model;Arterial Fatty Streak;Atherosclerosis;Biochemical;Biological;Biological Assay;Biological Process;Blood;Cardiovascular Diseases;CD36 gene;Cell surface;cell type;Chemical Injury;Cholesterol;Chronic;Clinical Markers;Colitis;Critical Pathways;Data;Deposition;dextran sulfate sodium induced colitis;Diabetes Mellitus;Disease;Disease susceptibility;Drug usage;Dyslipidemias;Endocytosis;Endosomes;Etiology;Event;Functional disorder;Genetic Models;Goals;gut inflammation;gut microbiota;High Density Lipoproteins;High Fat Diet;human disease;Immune signaling;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Inflammatory Response;innate immune pathways;innovation;Intake;Intestines;Knowledge;LDL Cholesterol Lipoproteins;Link;Lipids;Lipoproteins;Low Density Lipoprotein Receptor;Low-Density Lipoproteins;Macrophage;MAP Kinase Gene;Measures;Mediating;Metabolic;Metabolic Diseases;Metabolic syndrome;Metabolism;Modeling;Modification;Molecular Biology Techniques;Molecular Structure;murine colitis;Mus;Myeloid Cells;Names;new therapeutic target;NF-kappa B;novel;novel therapeutics;Obesity;oxidized low density lipoprotein;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Peripheral;Physiological;Physiology;Play;Predisposition;receptor;receptor mediated endocytosis;Receptor-Interacting Protein;Research;Risk Factors;Role;Signal Pathway;Signal Transduction;stem;Testing;Time;Tissues;western diet

PROJECT_TITLE: Novel Function of Native Low-Density Lipoprotein in Inflammation

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


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

PI_NAMEs: BALLARD, JIMMY D. (contact)

PROJECT_TERMS: Animal Model;Antibiotic Therapy;Antibiotics;Clostridioides difficile vaccine;Clostridium difficile;Data;Dedications;Disease;Dose;efficacy testing;Ensure;Environment;experience;experimental study;Generations;Goals;gut microbiome;Hamsters;Health;Individual;Infection;interest;Joints;Laboratories;Measures;Methods;microbiome;Modality;Modeling;Monitor;mouse model;Mus;Oklahoma;Oral;Outcome;pathogen;Predisposition;Procedures;programs;Public Health;Publications;Reagent;Recurrence;Recurrent disease;recurrent infection;Reproducibility;Reproduction spores;Research;Research Personnel;Research Project Grants;Services;Standardization;Vaccinated;Vaccination;vaccine candidate;vaccine efficacy;vaccine evaluation;vaccine response;Variant;Withdrawal

PROJECT_TITLE: Oklahoma C. difficile U19 Challenge Core


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

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

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

ORG_STATE: MA

PHR: Project Narrative Minimally invasive neural modulation at sub-millimeter spatial resolution remains a critical yet unmet biomedical need. We propose to build a minimally invasive neuromodulation device by taking advantage of a microwave split ring resonator design and validate its potential in suppression of seizures in a mouse model of epilepsy.

PI_NAMEs: CHENG, JI-XIN  (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Action Potentials;Address;Axon;Back;biomaterial compatibility;Biophotonics;Brain;Brain Injuries;brain tissue;Cellular Phone;Central Nervous System;Cephalic;Chemicals;Chronic;Clinical Treatment;Communication;Contrast Media;Copper;Couples;cranium;design;Development;Device or Instrument Development;Devices;Diameter;Doctor of Philosophy;electric field;Electromagnetic Energy;Epilepsy;Exposure to;Frequencies;Generations;Human;Image;Implant;In Vitro;in vivo Model;Label;Magnetism;Mediating;meter;Methods;microwave electromagnetic radiation;millimeter;minimally invasive;Modeling;Monitor;mouse model;multidisciplinary;Mus;neural;Neural Inhibition;neural stimulation;Neurons;neuroregulation;novel;Ocular dominance columns;Optics;Pacemakers;Pain management;Penetration;Peripheral Nervous System;Peripheral Nervous System Diseases;Photons;Reporting;Research;Research Personnel;Resolution;Risk;Scientist;Seizures;Spottings;Technology;Time;Tissues;Titanium;Toxic effect;Transcranial magnetic stimulation;ultrasound;Visual Cortex;wireless;wireless electronic;wireless fidelity;Work

PROJECT_TITLE: Sub-millimeter precision wireless neuromodulation using a microwave split ring resonator


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

PROJECT_TERMS: Adopted;Amino Acid Sequence;Animals;Antibody Response;Antigens;Cells;Cessation of life;Clinical Trials;Clostridioides difficile vaccine;Clostridium difficile;Combined Vaccines;Data;design;Disease;Drug Metabolic Detoxication;Effectiveness;Ensure;Epitopes;Event;experimental study;FDA approved;Futility;gastrointestinal;Generations;Genetic Engineering;Goals;Hamsters;Human;human monoclonal antibodies;Immune;immune activation;Immune response;Immunologic Memory;Immunosuppression;in vivo;Infection;Investigation;Mediating;Memory;memory recall;Modeling;mouse model;Mus;mutant;neutralizing antibody;next generation;novel;novel vaccines;pathogen;Phase III Clinical Trials;Polysaccharides;prevent;Production;Proteins;Publishing;Relapse;Reporting;response;Rodent;Structure;Testing;Toxic effect;Toxin;Toxoids;Vaccinated;Vaccination;vaccine candidate;vaccine effectiveness;Vaccines;Virulence;Virulence Factors;Work

PROJECT_TITLE: Enhancing C. difficile vaccination in the context of TcdB-mediated immunosuppression.


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: HOUSTON

ORG_NAME: METHODIST HOSPITAL RESEARCH INSTITUTE

PHR: Project Narrative We will determine 1) whether and how blood Tc9 cells induce tumor cell pyroptosis in tumor clearance via IL-9- and granzyme B-induced NFB-NLRP3-caspase-1-gasdermin activation; and 2) whether Tc9 cell persistence and function are mediated by Tc9 cell-secreted IL-9 and tumor-produced IL-1 and IL- 18 in vivo. We hypothesize that tumor-specific Tc9 subset may be superb effector T cells for cancer immunotherapy due to their capacity to induce both pyroptosis and apoptosis in tumor cells and utilize Tc9 cell-secreted IL-9 and tumor-produced IL-1 and IL-18 for their fitness, longevity, and function in vivo. Completing this project will reveal the importance and mechanism in induction of tumor pyroptosis by tumor-specific Tc9 cells and elucidate the mechanisms underlying the longevity and function of Tc9 cells in tumor microenvironment.

PI_NAMEs: YI, QING  (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Adoptive Cell Transfers;Adoptive Transfer;aged;antitumor effect;Antitumor Response;Apoptosis;Blood;cancer immunotherapy;cancer therapy;CASP1 gene;CASP3 gene;CD8-Positive T-Lymphocytes;Cell Death;Cell Survival;Clinical;cytokine;Effector Cell;effector T cell;fitness;Foundations;Granzyme;Growth;Hallmark Cell;Human;IL18 gene;improved;In complete remission;In Vitro;in vivo;Induction of Apoptosis;Inflammatory;Interferons;Interleukin-2;Interleukin-9;Label;life span;Longevity;Malignant Neoplasms;Mediating;Melanoma;neoplastic cell;novel;Patients;Play;PPBP gene;Production;response;Role;Signal Transduction;Solid;STAT3 gene;success;T-Lymphocyte;TC1 Cell;Testing;Therapeutic;Translating;tumor;tumor microenvironment

PROJECT_TITLE: Novel mechanism of induction of tumor pyroptosis by IL-9-secreting Tc9 cells

STUDY_SECTION: TTT

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


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Machine Learning and Artificial Intelligence

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE The major goals of this project are to develop a quantitative framework that enables objective delineation of Mendelian conditions, apply the framework to systematically delineate conditions across all genes known to underlie a Mendelian condition, and predict the number of conditions due to each gene. This framework will provide a fuller, unbiased characterization of the genotypic/phenotypic spectrum for all Mendelian conditions, enable more precise diagnoses and counseling of individuals with difficult to diagnose phenotypes, and accelerate the detection of new Mendelian conditions.

PI_NAMEs: CHONG, JESSICA XIAO-LING (contact)

PROGRAM_OFFICER_NAME: CHADWICK, LISA

PROJECT_TERMS: Acceleration;Affect;autism spectrum disorder;Clinical;Counseling;Data Set;Detection;Developmental Delay Disorders;Diagnosis;disease-causing mutation;gene discovery;Genes;Genome;genome-wide;Genomics;Genotype;Goals;Grouping;hearing impairment;Human;Human Genome;Individual;large datasets;Machine Learning;Maps;Methods;model organism;molecular diagnostics;Natural History;next generation;next generation sequencing;novel;Pathogenicity;Patients;Phenotype;Prognosis;Property;Recurrence;Risk;Variant;web-based tool;Work

PROJECT_TITLE: A next-generation morbid map of the human genome


PHR: NARRATIVE We will develop the foundations of an end-to-end platform for sequencing native, full-length proteins using unfoldase-coupled nanopore array technology. In principle, this platform could be used to directly determine the primary sequence, including certain post-translational modifications, of individual protein molecules found in human cells. This will provide unprecedented insight into proteoform diversity and its role in biological phenotypes and disease states such as cancer.

PI_NAMEs: NIVALA, JEFFREY MATTHEW (contact)

PROJECT_TERMS: 26S proteasome;Affinity;Amino Acid Sequence;Amino Acid Substitution;Amino Acids;base;Biochemical;Bioinformatics;Biological;Cell Culture Techniques;Cells;chemical conjugate;Collaborations;Combinatorics;Complex;Coupled;dark matter;Data;Databases;Detection;detection method;detector;Development;Devices;Disease;DNA;Engineering;Escherichia coli;Eukaryotic Cell;experience;Foundations;Genome;Grant;Human;Human Genome;In Vitro;Individual;insight;Label;Length;Malignant Neoplasms;markov model;Mass Spectrum Analysis;Methods;model organism;Modeling;Modification;Molecular Motors;Motor;Motor Activity;Movement;N-terminal;nanometer;nanopore;neural network;Nucleic acid sequencing;Nucleic Acids;Peptide Sequence Determination;Peptides;Performance;Phenotype;Pore Proteins;Post-Translational Protein Processing;Prokaryotic Cells;protein aminoacid sequence;Protein Isoforms;Protein translocation;Proteins;Proteome;Proteomics;Qualifying;Reagent;research and development;Research Personnel;Resolution;Role;Route;Sampling;Science;sensor;Sequence Analysis;sequencing platform;Signal Transduction;single molecule;Structure;Techniques;Technology;technology platform;Technology Transfer;Tertiary Protein Structure;Testing;tool;Touch sensation;Training;transcriptome;transcriptome sequencing;Translating;unfoldase;Variant

PROJECT_TITLE: Long-read single-molecule protein sequencing on an array of unfoldase-coupled nanopores


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

PROJECT_TERMS: Affinity;Antibodies;Antibody Response;antigen binding;Antigens;B cell repertoire;B-Lymphocytes;Bar Codes;beta-2 Microglobulin;Binding;Biological Assay;Breeding;Bypass;Cell Compartmentation;Cells;clinical efficacy;Clone Cells;Clostridioides difficile vaccine;Clostridium difficile;Data;Databases;Dependence;Disease;dysbiosis;Enteral;Fc Receptor;Generations;Genes;genomic locus;Genomics;Goals;Guanosine Triphosphate Phosphohydrolases;Human;human subject;IgG1;IgG2;Immune response;Immunization;Immunoglobulin A;Immunoglobulin G;Immunoglobulin M;Immunoglobulin Somatic Hypermutation;Immunoglobulin-Secreting Cells;Immunologic Memory;In Vitro;in vitro Assay;in vivo;Individual;Infection;insight;Intoxication;intraperitoneal;Intravenous;Life;Measures;Mediating;Memory B-Lymphocyte;memory encoding;Modeling;Monoclonal Antibodies;monoclonal antibody production;mouse model;Mus;neonatal Fc receptor;neutralizing antibody;neutralizing monoclonal antibodies;next generation sequencing;Oklahoma;Outcome;pathogen;Pathology;Patients;Pattern;Plasma Cells;premature;Production;programs;Property;Public Health;receptor binding;recruit;Recurrence;Recurrent disease;recurrent infection;Relapse;response;Serum;Severities;Severity of illness;Symptoms;Technology;Testing;Therapeutic Monoclonal Antibodies;Toxin;Transgenes;Vaccination;vaccination strategy;vaccine candidate;vaccine development;Virulence Factors;volunteer;Work

PROJECT_TITLE: Functions of human C. difficile-specific memory B cell-derived monoclonal antibodies