ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Malignantly transformed lymphocytes co-opt growth and survival signaling networks used by healthy lymphocytes. We have identified a new protein complex containing Pacs1 and Wdr37 that promotes lymphocyte survival through its effects on endoplasmic reticulum stress response pathways and calcium signaling. This proposal investigates how Pacs1-Wdr37 controls the survival of healthy and transformed lymphocytes with the intention of validating a new therapeutic target for lymphoid malignancies.

PI_NAMEs: NAIR-GILL, EVAN  (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: Acute;Affect;Antigen Receptors;Antigens;Apoptosis;Apoptotic;autoreactivity;B lymphoid malignancy;B-Cell Antigen Receptor;B-Cell Leukemia;B-Cell Lymphomas;B-Lymphocytes;Behavior;Binding;biological adaptation to stress;Calcium;Calcium Signaling;Cell Survival;cell transformation;Cells;Cellular Stress;Communication;Complex;Coupled;cytokine;Development;Disease;Down-Regulation;Endoplasmic Reticulum;endoplasmic reticulum stress;Exhibits;Failure;genetic approach;Genetic Screening;Genetic Transcription;Growth;Homeostasis;Human;humoral immunity deficiency;Immune;immune activation;immune function;Immune response;Immunity;Impairment;improved;In Vitro;in vivo;Inositol;insight;Intention;ITPR1 gene;knock-down;Lymphocyte;Lymphocyte Activation;Lymphoproliferative Disorders;Malignant - descriptor;Malignant lymphoid neoplasm;Measures;Mediating;Membrane;Mitochondria;Modeling;Mus;Mutagens;Mutation;new therapeutic target;novel;novel therapeutic intervention;overexpression;Oxidative Stress;Pathway interactions;pharmacologic;Phosphatidylinositols;Phosphotransferases;Play;Predisposition;preservation;prevent;Production;Proliferating;Protein Biosynthesis;protein complex;Protein Sortings;Proteins;Public Health;Reactive Oxygen Species;receptor;Receptor Signaling;release of sequestered calcium ion into cytoplasm;Reporter;response;Role;Signal Transduction;Stress;T-Lymphocyte;Testing;Therapeutic;therapeutic target;trafficking;tripolyphosphate;WD Repeat;Xenograft procedure

PROJECT_TITLE: The Role of Pacs1-Wdr37 inLymphocyte Quiescence and Survival

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging

ORG_CITY: SAN FRANCISCO

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE This Stimulating Access to Research in Residency program is designed to provide residents from diverse clinical backgrounds with the tools, mentorship, and support necessary to develop promising careers in aging research. As such, it addresses the need for clinician scientists who combine first-hand perspective on the care of older adults with the methodologic, collaborative, and communication skills necessary to conduct high- impact aging science. By including residencies and departments that do not already have a strong pre-existing tradition of aging research, this proposal also addresses the need for more diverse representation of different clinical perspectives in aging research.

PI_NAMEs: HUANG, ALISON  (contact)

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Address;Aging;aging related;Anesthesia procedures;Basic Science;California;career;career development;Caring;Clinical;clinical care;clinical investigation;Clinical Research;Clinical Sciences;clinically relevant;Communication;Communities;Credentialing;design;Discipline;dissemination research;Doctor of Philosophy;Educational Status;Ensure;epidemiology study;experience;Faculty;faculty mentor;Funding;Future;Goals;Gynecology;Health Services Research;human subject;human tissue;implementation research;Influentials;Institution;interest;Internal Medicine;Investigation;Medicine;Mentors;Mentorship;Methodology;Molecular Medicine;multidisciplinary;Neurology;older adult;Operative Surgical Procedures;Orthopedic Surgery;Outcomes Research;Pathway interactions;Patient Care;population based;Population Sciences;Positioning Attribute;programs;Psychiatry;recruit;Research;Research Methodology;Research Personnel;Research Project Grants;Research Support;Research Training;Residencies;Resources;San Francisco;Science;Scientist;skills;synergism;Time;tool;Training;Training Programs;Translating;Translational Research;translational scientist;Universities;Urology;Work

PROJECT_TITLE: Promoting Multidisciplinary Clinical and Translational Science in Aging by Resident Investigators


ADMINISTERING_IC: GM

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: SYRACUSE

ORG_DEPT: UROLOGY

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

ORG_STATE: NY

PHR: PROJECT NARRATIVE (RELEVANCE) The molecular chaperone Hsp90 is essential for maintaining protein homeostasis, which is critical in many maladies. This project will provide information on complex interplay between regulatory components of the Hsp90 chaperone in cells, which can also be uti- lized to enhance the sensitivity of cells to Hsp90 inhibitors.

PI_NAMEs: MOLLAPOUR, MEHDI  (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: ATP phosphohydrolase;Autoimmune Diseases;Binding;Biochemical;Biological Assay;Biophysics;Cells;chaperone machinery;Client;Clinical Trials;Complex;Coupled;Deceleration;Disease;drug sensitivity;enhancing factor;Goals;Heat-Shock Proteins 90;HSP 90 inhibition;Inflammatory;inhibitor;Knowledge;Malignant Neoplasms;Molecular;Molecular Chaperones;Neurodegenerative Disorders;Pharmaceutical Preparations;Phosphorylation;Phosphotransferases;Post-Translational Protein Processing;preclinical study;Proteins;proteostasis;Regulation;Signal Transduction;Signal Transduction Pathway;targeted treatment;TSC1 gene;Ubiquitination;Vision;Work

PROJECT_TITLE: Regulatory mechanisms of the Hsp90 chaperone machinery

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


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: Aurora

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: NARRATIVE Unhealthful dietary risk factors are rising in parallel with the global diabetes and obesity epidemics, yet the precise aspects of diet that causally influence metabolic disease and overall human health are unknown. Normal human genetic variation known to influence dietary intake will serve as the common human reference to identify comparable dietary traits across diverse studies, which can be combined with unprecedented statistical power for genomic meta-analysis. This approach will uncover novel and robust genetic associations with dietary intake that will enable the identification of diet’s causal role in metabolic health, informing dietary recommendations worldwide and prevent disease.

PI_NAMEs: COLE, JOANNE BURNETTE (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Address;Adherence;Alcohols;biobank;Biological Markers;Body mass index;burden of illness;Cardiometabolic Disease;career;Career Mobility;Clinical;Clinical Markers;cohort;Collaborations;Complex;Consumption;Data;Data Set;design;Diabetes Mellitus;Diet;dietary;Dietary intake;Dietary Intervention;Dietary Practices;Disease;Education;Enzymes;epidemiology study;Ethnic Origin;Etiology;experience;Faculty;follow-up;Food;food consumption;food environment;Food Patterns;Food Preferences;Foundations;Fruit;Genes;Genetic;genetic analysis;genetic association;Genetic Determinism;genetic epidemiology;Genetic Markers;Genetic study;genetic variant;Genetic Variation;genome wide association study;genome-wide;genomic locus;Genomics;Goals;Guidelines;Health;Heritability;Heterogeneity;Human;Human Genetics;improved;Individual Differences;Intake;Intervention Studies;Intervention Trial;Life Style;Link;Maps;Mendelian randomization;Mentors;Meta-Analysis;Metabolic;Metabolic Diseases;Metabolism;Methodology;Methods;Milk;mortality;multi-ethnic;Nomenclature;novel;nutrition;nutritional epidemiology;nutritional genomics;Obesity;Obesity Epidemic;Observational Study;olfactory receptor;Outcome;Pathway Analysis;Phase;phenome;Phenotype;Population;Positioning Attribute;preference;prevent;programs;Recommendation;Research;Research Personnel;Risk Factors;Role;Series;skills;success;Tea;Tissues;Training;trait;Translations;Work

PROJECT_TITLE: Genetically harmonized dietary intake and causal relationships with diabetes-related outcomes

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Genetics;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: SALT LAKE CITY

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Relevance: The project focuses on the mechanisms by which OCA-B governs the development of EAE, a preclinical mouse model of multiple sclerosis, and is most relevant to the evaluation and treatment of MS. Therefore, the findings from experiments in the proposal will advance the field significantly and have significant public health relevance.

PI_NAMEs: TANTIN, DEAN  (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: Alleles;Animals;Antigens;Autoimmune;Autoimmune Diabetes;Autoimmunity;autoreactive T cell;autoreactivity;B-Lymphocytes;Binding Sites;CD4 Positive T Lymphocytes;CD8B1 gene;cell type;Cells;Cervical lymph node group;Chromatin;chromatin modification;Clinical;Conditioned Reflex;Cytoprotection;Data;Development;diabetic;Docking;Drug Targeting;Environment;Evaluation;Excision;Experimental Autoimmune Encephalomyelitis;experimental study;Fertility;Flow Cytometry;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Gene Silencing;Genes;Genetic Polymorphism;Genetic Transcription;genome wide association study;Germ Lines;Goals;Histones;Human;Immune;immune function;Immune response;immunoregulation;Impairment;in vivo;Inbred NOD Mice;Inflammatory;inhibitor;Islets of Langerhans;Knockout Mice;Lightning;Lymphoid;Memory;memory CD4 T lymphocyte;Modeling;Molecular;mouse model;Multiple Sclerosis;multiple sclerosis treatment;Mus;neurotropic virus;Non obese;nuclear factors of activated T-cells;Organ;pathogen;Pathogenesis;Pathway interactions;Pattern;permissiveness;Phase;Phenotype;polarized cell;pre-clinical;preservation;public health relevance;recruit;Relapse;Reporter;Repression;response;Rest;single-cell RNA sequencing;T-Cell Development;T-Lymphocyte;TCF Transcription Factor;Technology;Testing;Therapeutic;transcription factor;Transcription Factor AP-1;Transplantation;Work

PROJECT_TITLE: Targeting OCA-B in multiple sclerosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-J(02)]


ADMINISTERING_IC: AA

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Social Determinants of Health;Substance Misuse

ORG_CITY: SEATTLE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE The career development plan will develop expertise of the investigator in the collection and analysis of passive mobile sensing data, with an emphasis on the application of machine learning methods. The proposed research study will use passive mobile sensing data in a large ambulatory assessment sample of regular drinkers, to develop models linking passive mobile sensing data with predictors of drinking episodes (such as stress, social context, and impulsiveness) and the drinking episodes themselves.

PI_NAMEs: KING, KEVIN MICHAEL (contact)

PROGRAM_OFFICER_NAME: ZHA, WENXING

PROJECT_TERMS: Accelerometer;Age;Alcohol abuse;Alcohol consumption;alcohol risk;alcohol use disorder;Alcoholic beverage heavy drinker;Alcohols;Algorithms;analytical method;Award;behavior prediction;Behavioral;burnout;career development;Cellular Phone;Collection;Consultations;Data;Data Reporting;data streams;design;Detection;Development;Development Plans;Diagnosis;diaries;disorder risk;drinking;drinking behavior;Ecological momentary assessment;Emotions;experience;feature selection;Fostering;Frequencies;Funding;Goals;handheld mobile device;Heavy Drinking;high risk drinking;Impulsivity;Independent Scientist Award;Individual;Intervention;K-Series Research Career Programs;Light;Link;Logistics;Machine Learning;machine learning method;marijuana use;marijuana user;Mental Health;Meta-Analysis;meter;Methodology;Methods;Mining;mobile sensing;mobile sensor;Modeling;Moods;open source;Outcome;outcome prediction;Parents;Participant;Patient Self-Report;perceived stress;personalized intervention;personalized medicine;Persons;Population;prediction algorithm;predictive modeling;Probability;Process;programs;Protocols documentation;Psychological reinforcement;real time monitoring;Recovery;Reporting;Research;Research Design;Research Personnel;Research Proposals;research study;Risk;Risk Factors;Sampling;sensor;Sleep;Social Environment;Stress;stressor;substance use;Techniques;Telephone;temporal measurement;Testing;Text Messaging;theories;Time;Training;young adult

PROJECT_TITLE: Passive mobile sensing and machine learning for the detection of drinking episodes

STUDY_SECTION: AA

STUDY_SECTION_NAME: Epidemiology, Prevention and Behavior Research Study Section[AA-2]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Opioid use disorder is a major epidemic in the United States; new, more effective, targeted treatments are critically needed to help prevent craving and relapse as current pharmacological treatments result in ~50% relapse. Focused ultrasound is a new, non-invasive, non-pharmacological method to modulate brain activity with high precision. Here, using an animal model, we will determine whether focused ultrasound can target and repair pathways that are dysfunctional in addiction to reduce craving and prevent relapse.

PI_NAMEs: LYNCH, WENDY JEAN (contact);VENTON, B. JILL

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: Acute;addiction;Address;Affect;Animal Model;Behavior;Behavioral;Brain;brain circuitry;Brain region;Clinic;Clinical Trials;craving;Cues;Data;Disease;Dopamine;Dose;drug craving;Epidemic;Female;Fentanyl;Focused Ultrasound;Focused Ultrasound Therapy;Future;Glutamates;Goals;Human;Hyperactivity;Incubated;Intervention;Investigation;Learning;male;Measures;Methods;Modeling;neuroadaptation;neurochemistry;Neurons;neuroregulation;Nucleus Accumbens;Opioid;opioid use disorder;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Phosphorylation;pre-clinical;Prefrontal Cortex;prevent;Rattus;Relapse;relapse prevention;repaired;Research;Resolution;Saline;Self Administration;Testing;Time;Translating;Translations;transmission process;treatment duration;Treatment Protocols;ultrasound;United States;Withdrawal

PROJECT_TITLE: An investigation of low-intensity focused ultrasound for addiction

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Digestive Diseases;Esophageal Cancer;Genetics;Human Genome;Prevention;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE (PUBLIC HEALTH RELEVANCE) Barrett’s esophagus (BE) is a pre-cancerous lesion which gives rise to esophageal adenocarcinoma (EAC), one of the most lethal of all cancers. In this proposal, we seek to elucidate the genes and biological pathways that mediate inherited genetic susceptibility to BE, through integration of new analytical tools and data with unique existing resources. Discoveries and insights from this study are expected to inform the development of novel strategies for prevention and treatment and ultimately help reduce the public health burden of BE/EAC.

PI_NAMEs: BUAS, MATTHEW FRANK (contact);YAN, LI

PROJECT_TERMS: 19p13;8p23.1;Address;Affect;Alleles;analytical tool;Barrett Esophagus;Bayesian Method;Biological;Biological Assay;Biological Process;biological specimen archives;Biology;Biopsy;Candidate Disease Gene;candidate identification;candidate validation;causal variant;Cell Line;cell type;Cells;Chromatin;Chronic;Chronic Disease;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Conserved Sequence;Data;Development;Disease;DNA Binding;Down-Regulation;Enhancers;Epidemiology;Esophageal Adenocarcinoma;Esophagogastric Junction;Esophagus;Evaluation;Exhibits;Future;Gastroesophageal reflux disease;Gene Expression;Gene Targeting;Genes;Genetic;Genetic Determinism;Genetic Predisposition to Disease;Genetic Variation;genome wide association study;genome-wide;Genotype;Genotype-Tissue Expression Project;Goals;Healthcare;in silico;Incidence;indexing;Inflammation;Informatics;Inherited;Injury;insight;Intervention;knock-down;Lesion;Link;Luciferases;Malignant Neoplasms;Maps;Mediating;Mediator;member;Methods;Molecular;mortality;Mucous Membrane;Network-based;novel;novel strategies;overexpression;Pathogenesis;Pathway Analysis;Pathway interactions;Patients;Phase;Predisposition;premalignant;prevent;Prevention;Prevention strategy;Preventive;Probability;Promoter Regions;Public Health;public health relevance;Reflux;Regulatory Element;Reporter;Research;Resources;Risk;risk variant;Scheme;screening;Signal Transduction;single-cell RNA sequencing;statistics;success;Susceptibility Gene;System;Testing;The Cancer Genome Atlas;Tissues;trait;Transcriptional Regulation;transcriptome sequencing;transcriptomic profiling;Translating;Untranslated RNA;Variant;virtual;Weight;Work

PROJECT_TITLE: Genetic susceptibility to Barrett's esophagus: From GWAS to biology

STUDY_SECTION: GHD

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Cardiovascular;Emerging Infectious Diseases;Genetics;Heart Disease;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza

ORG_CITY: Columbus

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: NARRATIVE Influenza virus can damage the heart, though this is a poorly understood aspect of influenza pathogenesis. We are investigating how and why specific virus strains traffic to the heart from the lung, how these viruses damage the heart, and how the immune system provides both beneficial and nonbeneficial effects during infection. This work will identify new strategies to prevent or treat influenza-associated cardiac dysfunction.

PI_NAMEs: YOUNT, JACOB  (contact)

PROGRAM_OFFICER_NAME: ARNOLD, MICHELLE MARIE

PROJECT_TERMS: 1918 influenza pandemic;Address;Animal Model;Area;Attenuated;Autopsy;Bone Marrow;Cardiac;Cardiac Myocytes;Cell membrane;Cells;Chimera organism;Chromosome Mapping;Classification;Clinical;Custom;Data;Dose;Endowment;Engineering;Event;Fibrosis;Functional disorder;Funding;Genetic;Genetic Determinism;genetic risk factor;Heart;heart cell;heart damage;Hematopoietic;Hospitalization;Human;human mortality;Immune;Immune system;Immunity;Individual;Infection;Inflammation;Inflammatory;Influenza;influenza infection;influenza virus strain;influenzavirus;Innate Immune System;innovation;Integral Membrane Protein;Interferons;Knockout Mice;Knowledge;Laboratory mice;Lung;Lung infections;lung injury;Measurement;Modeling;Monitor;mouse model;Mouse Strains;Mus;Mutation;Myocardial dysfunction;Myocarditis;Natural Immunity;new pandemic;novel;Organ;pandemic influenza;Pathogenesis;Pathogenicity;Pathology;Patients;Population;Positioning Attribute;Predisposition;prevent;Process;Proteins;Reassortant Viruses;Recombinants;reconstitution;Reporting;Research;Resistance;reverse genetics;Role;seasonal influenza;systemic inflammatory response;Testing;theories;Tissues;trafficking;Tropism;Vaccination;Viral;Viral Genes;Viral Proteins;Viremia;Virus;Virus Diseases;virus genetics;virus host interaction;Virus Replication;Work

PROJECT_TITLE: Mechanisms of innate resistance to virus infections

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Heart Disease;Kidney Disease

ORG_CITY: BOSTON

ORG_NAME: TUFTS MEDICAL CENTER

ORG_STATE: MA

PHR: NARRATIVE Reduced kidney function is highly prevalent among patients with heart failure, and has been consistently shown to be one of the most powerful risk factors for poor clinical outcomes. Acute declines in kidney function, on the other hand, remain poorly understood and how they are related to outcomes including longer term kidney function decline and cardiovascular events is controversial. This study will examine acute kidney function declines in the context of three critical factors—congestion, cardiac hemodynamics and neurohormonal activity—in order to better understand mechanisms and develop clinical phenotypes of the acute cardiorenal syndrome.

PI_NAMEs: MCCALLUM, WENDY  (contact)

PROGRAM_OFFICER_NAME: GREER, RAQUEL CHARLES

PROJECT_TERMS: Acute;Adoption;adverse outcome;arm;Biological Assay;Biological Markers;Biostatistical Methods;Blood specimen;Cardiac;Cardiorenal syndrome;Cardiovascular system;career development;Catheters;Central venous pressure;Clinical;Clinical Management;clinical phenotype;Collaborations;Cues;Data;Data Analyses;Data Collection;Data Set;Development Plans;Electronic Health Record;Enrollment;epidemiology study;Event;experience;functional decline;Functional disorder;Funding;Future;glomerular filtration;Glomerular Filtration Rate;Goals;Heart failure;hemodynamics;high risk;Hospitalization;Hospitals;Immersion;improved;improved outcome;indexing;Informatics;Institution;Intervention Studies;Joints;Left;Literature;Manuscripts;Measures;Medical center;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methodology;Modeling;mortality;Outcome;Pathway interactions;Patient Admission;patient population;Patient Recruitments;Patients;Plasma;Population;pressure;Productivity;prognostic;prospective;Prospective Studies;Pulmonary artery structure;Renal function;Renin;Research;Research Design;Risk Factors;Side;targeted treatment;Testing;tool;Training;Universities;Ventricular

PROJECT_TITLE: Relation between acute changes in kidney function with clinical outcomes among patients with heart failure

STUDY_SECTION_NAME: Kidney, Urologic and Hematologic Diseases D Study Section[DDK-D]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Dental, Oral, and Craniofacial Disease;Disability Research;Neurosciences

PHR: Project Narrative Patients with facial paralysis have a severe facial soft tissue disability that includes impairments in movements, particularly facial expressive behaviors. We have developed and refined novel 3D dynamic and static quantitative (objective) measures and dynamic modeling comparisons for characterization of facial disability and outcomes of treatment in patients with facial paralysis. Thus, the goals of this study are to determine outcomes of mid-facial reanimation surgeries in patients with more extensive and permanent, unilateral, paralysis of varied etiology and presentation using patient-centered 3D objective facial measures/modeling and patient-centered measures of facial appearance and well-being.

PI_NAMEs: TROTMAN, CARROLL ANN (contact)

PROGRAM_OFFICER_NAME: GRISIUS, MARGARET

PROJECT_TERMS: 3-Dimensional;Affect;Age;animation;Anxiety;Appearance;Area;Behavior;Botulinum Toxins;Characteristics;cleft lip and palate;Client satisfaction;comparison control;Computer software;Control Groups;Data;Decision Making;Defect;Dimensions;disability;Disability outcome;Disease;Disparate;Esthetics;Etiology;Evaluation;Face;facial disfigurement;Facial nerve structure;Facial paralysis;Goals;Grant;Health Care Costs;Image;Impairment;Incidence;Intervention;Literature;Measurement;Measures;Medical;Methods;Modeling;Movement;Muscle;Nerve;nerve supply;novel;Observational Study;Operative Surgical Procedures;Outcome;Outcome Assessment;Outcome Study;Paralysed;Pathologic;patient oriented;Patient-Focused Outcomes;Patients;Perception;Personal Satisfaction;Photography;Process;programs;prospective;Questionnaires;reconstruction;Recovery;repaired;Reporting;Research;Resolution;satisfaction;Self Perception;Severities;sex;SF-36;Smiling;Social Interaction;soft tissue;Surgeon;Syndrome;Testing;three dimensional structure;Three-dimensional analysis;three-dimensional modeling;Trauma;Treatment outcome;treatment planning;Trigeminal nerve structure;tumor;two-dimensional;United States;United States National Institutes of Health

PROJECT_TITLE: 3D Dynamic and Patient-Centered Outcomes of Facial Reanimation Surgery in Patients with Facial Paralysis

STUDY_SECTION: BMIO

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


NIH_SPENDING_CATS: Digestive Diseases;Infectious Diseases

PHR: Project Narrative Parasitic worms, allergens, and some protists all trigger a “type 2” immune response, but we do not yet fully understand the underlying mechanisms of immune sensing and regulation. More than 1 billion individuals are currently infected with worms, and the incidence of allergies is rising worldwide. By studying the role of epithelial tuft cells in type 2 immunity, we hope to discover novel targets for therapeutic intervention in helminth infection and allergy.

PI_NAMEs: VON MOLTKE, JAKOB H. (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Acetylcholine;Allergens;Allergic Disease;Attention;Biological Assay;burden of illness;Cell secretion;Cells;cytokine;Effector Cell;Electron Microscopy;Eosinophilia;Epithelium;Event;experimental study;Frequencies;Funding;Gene Expression Profile;Gene Expression Profiling;Gene Modified;Goals;Goblet Cells;Health;helminth infection;Helminths;Human;Hyperplasia;Hypersensitivity;Immune;immune function;Immune response;Immunity;Immunology;In Vitro;in vitro Assay;in vivo;Incidence;Individual;Infection;Inflammation;innovation;Interleukin-13;Interleukin-5;Intestines;Ions;Laboratories;Leukotriene C4;Leukotrienes;Ligands;Link;Lipids;Liquid substance;Lung;Lymphoid Cell;Measures;Membrane;microbial;Modeling;Morphology;mouse model;Mouse Strains;Mucous body substance;Mucus-Secreting Cell;Mus;Neuromedin U;Neuropeptides;new epidemic;new therapeutic target;NF-kappa B;novel;nuclear factors of activated T-cells;paracrine;Pathway interactions;Peptides;Physiology;Positioning Attribute;Prevalence;Production;Publishing;Reagent;Regulation;release of sequestered calcium ion into cytoplasm;response;Role;Sensory;Sentinel;Signal Induction;Signal Transduction;skills;Small Intestines;Stimulus;Succinates;Testing;Therapeutic Intervention;Tissues;tool;Transcription Factor AP-1;Transgenic Mice;Work

PROJECT_TITLE: Tuft cell effector functions in the small intestine

STUDY_SECTION: GMPB

STUDY_SECTION_NAME: Gastrointestinal Mucosal Pathobiology Study Section[GMPB]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Genetic Testing;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurodegenerative;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_DEPT: NEUROLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE  This study will investigate the impacts of receiving personal information about risk of Alzheimer's disease related to the genetic susceptibility gene APOE, among Latinos who reside in three communities in northern Manhattan. Participants will be randomly assigned to receive risk information based on either (a) self-reported Latino ethnicity and family history of Alzheimer's disease or (b) the same information plus their APOE genotypes. Surveys and in-depth qualitative interviews at 6-weeks, 9-months, and 18-months after they receive risk information will be used to evaluate their responses. The results will provide important information for tailoring genetics education and counseling interventions to Latinos.

PI_NAMEs: OTTMAN, RUTH  (contact);SIEGEL, KAROLYNN

PROGRAM_OFFICER_NAME: HETTINGER, JANE CECELIA

PROJECT_TERMS: Acculturation;Address;Adult;adverse outcome;Aging;Alzheimer's Disease;Alzheimer's disease risk;Anxiety;anxiety symptoms;Apolipoprotein E;apolipoprotein E-4;behavior change;Behavioral;Belief System;Caribbean Hispanic;Caucasians;Characteristics;Cognition;Communities;contextual factors;coping;Coping Skills;Counseling;cultural values;Data;depressive symptoms;design;Disclosure;Disease;Distress;Dominican;Education;emotion regulation;Enrollment;ethnic minority population;Ethnic Origin;Ethnic Population;European ancestry;Evaluation;Event;experience;Family;Family history of;General Population;Genetic;genetic information;genetic predictors;Genetic Predisposition to Disease;Genetic Risk;Genetic Status;genetic testing;Genotype;Health behavior;Height;high risk;Homozygote;improved;Incidence;Influentials;interest;Intervention;Interview;Investigation;Late Onset Alzheimer Disease;Latino;Latino Population;Learning;lifetime risk;Lived experience;Masks;Measures;Memory;Mental Depression;Methodology;Methods;Modeling;Modification;Outcome;Participant;Patient Self-Report;Pattern;performance tests;Persons;Population;presymptomatic testing;Prevention trial;primary endpoint;Psychosocial Assessment and Care;psychosocial outcome;Qualitative Research;Questionnaires;Randomized;Recording of previous events;Research;response;Risk;Risk Assessment;Risk Estimate;Risk Marker;Running;Sampling;secondary endpoint;social stigma;Source;standardize measure;Stress and Coping;Study of Latinos;Subgroup;Surveys;Susceptibility Gene;Telephone;Testing;Time;Treatment/Psychosocial Effects;Washington;Work

PROJECT_TITLE: Impacts of receiving Alzheimer's disease genetic risk information among Latinos in northern Manhattan

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-SEIR-B(80)]


PHR: PROJECT NARRATIVE Human cytomegalovirus (HCMV) infection is associated with a myriad of chronic inflammatory organ diseases, which can lead to multi-organ failure in transplant recipients. Inflammatory organ diseases associated with HCMV are a direct consequence of viral replication in tissue and subsequent systemic spread to multiple organ sites mediated by infected circulating blood monocytes. This project will seek to provide a proof-of-concept that targeting unique alterations to the cellular programing of infected cells during HCMV infection can be utilized to simultaneously inhibit virus replication and/or viral dissemination.

PI_NAMEs: CHAN, GARY CHING TAO (contact)

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: Ablation;Adverse effects;Advocate;Animal Model;antagonist;Anti-viral Agents;Anti-viral Therapy;Attenuated;Biological;biological adaptation to stress;Bone Marrow Cells;cell type;Cells;Cessation of life;Chronic;Clinical;Cytomegalovirus;Cytomegalovirus Infections;Data;design;Development;Disease;Distal;drug discovery;drug efficacy;Drug Kinetics;Drug toxicity;efficacy evaluation;Failure;Fibroblasts;Foundations;Future;Genes;Genetic;genetic approach;heat-shock factor 1;Heat-Shock Response;high risk;Human;human model;human tissue;Immunocompromised Host;immunosuppressed;improved;in vivo;in vivo evaluation;Infection;Infiltration;Inflammatory;inflammatory milieu;inhibitor;insight;Kinetics;knock-down;latent infection;Lytic;lytic replication;Macrophage;Mediating;Monitor;monocyte;mouse model;Multiple Organ Failure;Mus;Myeloid Cells;neonate;new therapeutic target;novel;Nuclear;Opportunistic Infections;Organ;organ transplant recipient;Organ Transplantation;Pathogenesis;Peripheral;permissiveness;Persons;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Pharmacology;prevent;Prophylactic treatment;Proteins;Regimen;Resistance;Role;Site;Skin;standard of care;Stress;Testing;Therapeutic;Tissues;tool;transcription factor;transcriptome;transcriptome sequencing;translatome;transplant model;Transplant Recipients;Transplantation;Viral;Viral Genome;Viral Physiology;viral rebound;Virus;Virus Replication;virus testing

PROJECT_TITLE: Targeting Nuclear HSF1 as a Novel Anti-HCMV Strategy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-B(82)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Drug Abuse (NIDA only);Methamphetamine;Neurodegenerative;Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE Methamphetamine is a highly addictive psychostimulant that can induce significant neuronal damage. Pilot studies indicated that repeated methamphetamine administration resulted in neuron loss in the substantia nigra pars compacta and locus coeruleus but not the ventral tegmental area or dorsal raphe. Our studies are aimed at understanding why some neuronal populations are vulnerable to methamphetamine-induced neurodegeneration while some are resistant; moreover, by determining mechanisms underlying vulnerability versus resistance we hope to identify neuroprotective strategies.

PI_NAMEs: GRAVES, STEVEN MICHAEL (contact)

PROGRAM_OFFICER_NAME: TSAI, SHANG-YI ANNE

PROJECT_TERMS: Abstinence;Achievement;Antioxidants;ATP Synthesis Pathway;Axon;Back;Behavioral;Biosensor;Brain;Buffers;calbindin;Chronic;conditioned fear;Dangerousness;Data;density;Dependence;Dopamine;Dorsal;experimental study;genetic approach;genetic manipulation;Human;Immunohistochemistry;Impaired cognition;Impairment;Induced Neurons;Laser Scanning Microscopy;locus ceruleus structure;Metabolism;Methamphetamine;methamphetamine abuse;Mitochondria;monoamine;Mus;Nerve Degeneration;neuron loss;neuronal cell body;Neurons;neuroprotection;Neurotransmitters;Norepinephrine;novel;object recognition;pars compacta;Pattern;pharmacologic;Pilot Projects;prevent;Proteins;psychostimulant;Resistance;Role;Serotonin;Slice;Stress;Substantia nigra structure;Testing;two-photon;Ventral Tegmental Area;Vesicle;vesicular monoamine transporter 2;Vulnerable Populations

PROJECT_TITLE: Methamphetamine, mitochondria, and neurodegeneration

STUDY_SECTION: NOMD

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


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

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Narrative Postoperative delirium is a common and significant cognitive complication after major surgery in older people. Nonetheless, luck of its underlying pathophysiology delays advances in prevention and treatment of postoperative delirium. In this study, we aim to identify age and gender-dependent microglia-mediated molecular mechanisms underlying postoperative cognitive impairments in mouse models and also examine inhibition of glutaminase may reverse the abdominal surgery-induced microglia-mediated neuroinflammation, which may alleviate age-dependent postoperative cognitive impairments.

PI_NAMEs: KAMIYA, ATSUSHI  (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Abdomen;Acute;Adult;Affect;Age;age related;aged;Aging;Alzheimer's Disease;Attention;Behavior;Behavioral;Brain;Brain Diseases;Brain Injuries;Brain region;C57BL/6 Mouse;Cells;Clinical;Cognition;Cognitive;cognitive function;Complication;cytokine;Delirium;Dementia;design;Disease;disease model;Drug Targeting;Elderly;Environment;Enzymes;Etiology;excitotoxicity;experimental group;experimental study;extracellular;Female;Functional disorder;Gender;Gene Expression Profile;Gene Expression Profiling;Genes;Glutamates;Glutaminase;Glutamine;glutamine analog;Heterogeneity;Hippocampus;Immune;Impaired cognition;Impairment;improved;Infiltration;Inflammation;Inflammatory;inhibitor;Link;male;Medial;Mediating;Metabolic;Microglia;Molecular;molecular phenotype;Molecular Profiling;monocyte;mouse model;Mus;neural;neuroinflammation;Neurotransmitters;Norleucine;old mice;Older Population;Operative Surgical Procedures;Oral;Penetration;pharmacologic;Play;postoperative delirium;Postoperative Period;Prefrontal Cortex;prevent;Prevention;Prodrugs;Production;Public Health;Reporting;Research;Risk;Role;sex;single-cell RNA sequencing;Stress;Synapses;Syndrome;systemic inflammatory response;transcriptome;transcriptome sequencing;Up-Regulation

PROJECT_TITLE: Targeting age and gender-dependent microglia-mediated mechanisms underlying postoperative cognitive impairment for treatment of delirium in the elderly


NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SALSBURY COVE

ORG_NAME: MOUNT DESERT ISLAND BIOLOGICAL LAB

ORG_STATE: ME

PHR: Project Narrative Cellular pluripotency in the germline is maintained through processes within cytoplasmic assemblies called germ granules. Core germ-granule proteins are conserved in almost all animals, frequently repurposed during development, and re-expressed in multi-potent cancers. Understanding the function of individual germ-granule proteins, the purpose and conditions of their assembly, and their capacity for cellular reprogramming, will lead to applications that improve reproductive health, regeneration, and cancer therapeutics.

PI_NAMEs: UPDIKE, DUSTIN LYNN (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: 3' Untranslated Regions;Animals;Binding;Caenorhabditis elegans;Cell Nucleus;Cell Reprogramming;Cells;Chromatin;Complex;Cytoplasm;Cytoplasmic Granules;Development;drug discovery;Ensure;Event;experimental study;follow-up;Gene Expression;Germ;Germ Cells;Germ Lines;Glycine;healing;Human;improved;in vivo;Individual;Malignant Neoplasms;Messenger RNA;Mutation;Names;Natural regeneration;Nematoda;neuronal cell body;novel;Nuclear;Pathway interactions;pluripotency;Process;Proliferating;Proteins;Regenerative capacity;Reproductive Health;Research;RNA;somatic cell nuclear transfer;Sterility;Therapeutic;Translation Initiation;Visualization;wound

PROJECT_TITLE: The function of germ granule processes that maintain pluripotency in the C. elegans germline

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: Los Angeles

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative Epistasis causes genetic variants to exhibit different effects depending on the genotypic contexts in which they occur. This context dependence makes it hard to achieve a predictive understanding of the relationship between individuals’ genomes and traits. We will improve understanding of epistasis by (1) studying how epistasis causes CRISPR perturbations to show different effects in distinct individuals and (2) using chromosome synthesis to characterize the extent of epistasis between related taxa.

PI_NAMEs: EHRENREICH, IAN MICHAEL (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Bar Codes;base;Cells;Chromosomes;Cloning;Clustered Regularly Interspaced Short Palindromic Repeats;Code;combinatorial;CRISPR interference;Data;Dependence;Disease;DNA;Exhibits;Genes;Genetic;Genetic Epistasis;genetic variant;Genome;genomic data;Genotype;Goals;Health;High temperature of physical object;Human;improved;Individual;Induced Mutation;insight;Maps;Meiosis;Methods;Molecular;Partner in relationship;personalized genomics;Phenotype;Population;portability;prevent;programs;Proteins;Research;Shapes;Techniques;trait;Variant;Work;Yeasts

PROJECT_TITLE: Characterizing epistasis in yeast using CRISPR and chromosome synthesis

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biotechnology;Eye Disease and Disorders of Vision;Neurosciences

ORG_DEPT: ANESTHESIOLOGY

PHR: Project Narrative: The technology proposed here will lead to new techniques for spatial and temporal control of neuromodulator signaling in the brain. The light sensitive tools we will develop will have multi-functional abilities to allow for discrete control over time and space of critical receptor signaling pathways in the awake- behaving brain. These new optogenetic tools will allow neuroscientists and biologists to have unprecedented resolution in uncovering the basis for brain diseases, and have translational potential for delivery of new treatments for brain disorders.

PI_NAMEs: BERNDT, ANDRE ;BRUCHAS, MICHAEL R. (contact);SHALEV-BENAMI, MORAN ;YIZHAR, OFER

PROGRAM_OFFICER_NAME: TALLEY, EDMUND M

PROJECT_TERMS: Activities of Daily Living;Acute;Address;Adoption;Animals;Arrestins;awake;Behavior;behavior measurement;Behavioral;Behavioral Assay;Biological Assay;biological systems;Biosensor;Brain;Brain Diseases;BRAIN initiative;brain tissue;Calcium;candidate selection;Cell Culture Techniques;cell type;Color;Communication;Communities;Complex;Coupled;Coupling;Cryoelectron Microscopy;Databases;Development;Dissection;Electrophysiology (science);Engineering;Fiber;G-Protein-Coupled Receptors;Goals;GTP-Binding Proteins;high throughput screening;Image;imaging approach;In Vitro;in vivo;innovation;Ions;Kinetics;Laboratories;Libraries;Light;Mammalian Cell;Membrane;mutant;Mutation;neural;neural circuit;Neuromodulator;neuronal circuitry;Neurons;neurophysiology;neuroregulation;Neurosciences;Neurotransmitters;new technology;next generation;novel;Opsin;Optics;optogenetics;Organism;Pathway interactions;Pharmacology;Photometry;Photophobia;Physiology;Property;Protein Analysis;Protein Engineering;Publishing;receptor;Receptor Signaling;Resolution;Rhodopsin;scaffold;Scheme;sensor;Series;Signal Pathway;Signal Transduction;Signaling Protein;simulation;Site;Slice;spatiotemporal;Specificity;Structural Biologist;structural biology;Structure;Synapses;System;Techniques;Technology;Testing;Time;tool;Translating;translational potential;two-photon;Validation;Variant;Work

PROJECT_TITLE: Next Generation Opto-GPCRs for Neuromodulatory Control


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Liver Disease;Lung;Microbiome;Organ Transplantation;Transplantation

ORG_CITY: PITTSBURGH

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Carbapenem-resistant Enterobacteriaceae (CRE) are major pathogens among lung/liver transplant recipients, who continue to experience infections years after transplant. I hypothesize that chronic CRE colonization and late-onset infection are caused by persistence of CRE that colonize the gut early after transplant, a process which is associated with a state of chronic gut dysbiosis and the emergence of antibiotic tolerance. I will longitudinally characterize serial CRE isolates from patients and study the gut microbiome environment in which CRE colonization, persistence, and infection occur, which will lead to future studies evaluating the mechanisms of tolerance among CRE isolates after transplant, and of strategies to modify the microbiome of transplant recipients with CRE infections.

PI_NAMEs: HAIDAR, GHADY  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acceleration;Advisory Committees;Antibiotic Resistance;antibiotic tolerance;Antibiotics;Attention;Bacteremia;Bacteria;Bacteroides;Bacteroidetes;Biometry;carbapenem resistance;carbapenem-resistant Enterobacteriaceae;Ceftazidime;Characteristics;Chronic;Clinical Research;clinical risk;Colistin;Communicable Diseases;Data;design;Detection;Disease;drug resistant bacteria;dysbiosis;Enterobacteriaceae Infections;Environment;Event;Exhibits;experience;fecal microbiome;Feces;Firmicutes;Future;Genetic;Genetic study;genomic epidemiology;Genomics;Goals;Gram-Negative Bacteria;gut colonization;gut dysbiosis;gut microbiome;gut microbiota;high risk;Imipenem;In Vitro;Individual;Infection;insight;liver transplantation;Lung;lung microbiome;Lung Transplantation;Malignant Neoplasms;Medical center;Medicine;Mentored Patient-Oriented Research Career Development Award;Mentors;Meropenem;metagenomic sequencing;microbial;microbiome;microbiome research;microbiome therapeutics;microbiota;microbiota transplantation;Morbidity - disease rate;mortality;Multi-Drug Resistance;Mutation;novel;organ transplant recipient;Organ Transplantation;pathogen;Pathogenesis;Patients;Physicians;Plasmids;Pneumonia;post-transplant;prevent;Prevention strategy;Process;professor;prospective;Prospective Studies;Proteobacteria;rational design;Rectum;recurrent infection;Research;Research Personnel;Resistance;Resistance development;Ribosomal RNA;Risk Factors;Sequence Analysis;skill acquisition;skills;Solid;Source;stool sample;Swab;Technical Expertise;Testing;Time;Training;translational physician;translational scientist;translational study;Transplant Recipients;Transplantation;treatment strategy;trial design;Universities;whole genome;Work

PROJECT_TITLE: The Gut Microbiome in Carbapenem-Resistant Enterobacteriaceae Colonization, Persistence, Infection, and Tolerance after Lung or Liver Transplantation

STUDY_SECTION: AITC

STUDY_SECTION_NAME: Allergy, Immunology, and Transplantation Research Committee[AITC]


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

ORG_CITY: BURLINGTON

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: Project Narrative Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pelvic pain syndrome, exacerbated by stress, with an enormous impact on quality of life. We hypothesize that increases in urinary frequency and pelvic pain that accompany BPS/IC reflect changes in the expression, function and interactions of neurochemical mediators and the sensory transducer, TRPV4/Ca2+, in the sensory components of the micturition reflex that favor a pro-excitatory state. These studies will provide insights into novel targets with the potential to treat or prevent disease.

PI_NAMEs: VIZZARD, MARGARET ANN (contact)

PROGRAM_OFFICER_NAME: MULLINS, CHRISTOPHER V

PROJECT_TERMS: Acute;Address;Affect;afferent nerve;Animal Model;Apoptosis;Attenuated;Biological Assay;Bladder;Bladder Dysfunction;bladder pain;Cations;Cells;Chronic;chronic pelvic pain;Clinical;Clinical Trials;confocal imaging;Conscious;Coupled;Cyclophosphamide;Cystitis;Disease;Dose;effective therapy;Enzyme-Linked Immunosorbent Assay;Esthesia;Event;Exocytosis;Experimental Models;Flare;Frequencies;Functional disorder;Human;Image;Immunohistochemistry;improved;Increased frequency of micturition;innovation;insight;interdisciplinary approach;Interruption;Interstitial Cystitis;Knockout Mice;Laboratories;Link;MAP Kinase Gene;Mediating;Mediator;member;Micturition Reflex;Modeling;mouse model;multidisciplinary;Mus;neurochemistry;NGFR Protein;novel;overexpression;Pain;Pain Disorder;pain perception;Pathway interactions;Patients;Pelvic Pain;Pelvis;pharmacologic;prevent;protein expression;Psychological Stress;Publishing;Quality of life;receptor;Recovery;Research;Resistance;response;Role;Sensory;Signal Pathway;Signal Transduction;Signs and Symptoms;small molecule;Spinal cord injury;Spinal Ganglia;Stress;Symptoms;System;Testing;Tissues;Transcript;Transducers;Transgenic Mice;urinary;Urination;Urothelial Cell;Urothelium;Vanilloid;Work

PROJECT_TITLE: Cystitis-induced bladder dysfunction and pain

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-B(90)]


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Complementary and Integrative Health;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Physical Activity;Social Determinants of Health

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE: The K24 award will provide me with protected time to engage in targeted mentoring in technology enhanced mind-body approaches to promising trainees from diverse backgrounds within a diverse, creative and supportive research environment. It will afford me with valuable time to increase my own mentoring, training and research skills in novel and timely research areas that are in line with NCCIH priorities.

PI_NAMEs: VRANCEANU, ANA-MARIA  (contact)

PROGRAM_OFFICER_NAME: MUDD, LANAY MARIE

PROJECT_TERMS: Accelerometer;Acute;Acute Pain;Aging;Area;Award;barrier to care;Behavioral Medicine;Boston;brain health;Brain Injuries;Bypass;career;career development;Caregivers;Chronic;Chronic Disease;chronic pain;Clinical;Clinical Psychology;Clinical Research;Clinical Trials;Clinical Trials Design;Complementary Health;Consultations;Creativeness;Critical Care;Dedications;Department of Defense;Development;Devices;digital health;Doctor of Philosophy;educational atmosphere;Enhancement Technology;Environment;ethnic diversity;ethnic minority;Family;Feedback;First Generation College Students;fitbit;Foundations;Funding;Future;General Hospitals;Goals;Grant;Health;health disparity;Hospital Departments;Immigrant;informal caregiver;innovation;Institution;Integrative Medicine;International;Internships;Leadership;life span;lifestyle intervention;Link;low socioeconomic status;Manuscripts;Massachusetts;Medical;Medical center;medical schools;meetings;Mentors;Mid-Career Clinical Scientist Award (K24);Mind-Body Intervention;Mind-Body Method;mind/body;mobile application;Monitor;Multi-Institutional Clinical Trial;National Center for Complementary and Integrative Health;Neurofibromatoses;novel;Outcome;Patient Care;Patients;Peer Review;Persons;Postdoctoral Fellow;pre-doctoral;Principal Investigator;programs;Psychiatry;Psychologist;Publishing;racial diversity;racial minority;Research;Research Activity;Research Assistant;Research Personnel;Resources;Rewards;rural area;Scientist;sensor;skills;Societies;System;Talents;Technology;Time;Training;Training Activity;Underserved Population;Work

PROJECT_TITLE: Mentoring in technology enhanced mind body and lifestyle interventions


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Biotechnology;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: STANFORD

ORG_DEPT: SURGERY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Recent studies have identified a number of similarities between cancer and cardiovascular disease. Indeed, the uncontrolled growth of ‘stem-like’ cells in the blood vessel wall may cause those vessels to narrow and become obstructed. Learning how to target those cells for clearance may lead to new therapies for heart attack and stroke - leading killers in the United States.

PI_NAMEs: LEEPER, NICHOLAS JAMES (contact)

PROGRAM_OFFICER_NAME: OLIVE, MICHELLE

PROJECT_TERMS: atherogenesis;Atherosclerosis;biobank;Blood Vessels;Cardiovascular Diseases;Cells;Clonal Expansion;Color;Complement;Data;Development;Disease;Excision;flexibility;Goals;Greek;Growth;Heart Diseases;Human;insight;interdisciplinary collaboration;Learning;Malignant Neoplasms;Mission;Modeling;Myocardial Infarction;Natural Immunity;next generation;novel;novel therapeutics;Patients;Phagocytes;Phenotype;Population;prevent;programs;Research Personnel;Resistance;single-cell RNA sequencing;Smooth Muscle Myocytes;Specimen;stem;stem cells;stem-like cell;Stroke;Testing;tool;Tracer;Training;Transgenic Animals;translational therapeutics;United States;United States National Institutes of Health;vascular inflammation;Vascular Smooth Muscle

PROJECT_TITLE: Clonal expansion, resistance to efferocytosis and innate immunity in atherosclerosis


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Conditions Affecting the Embryonic and Fetal Periods;Cost Effectiveness Research;HIV/AIDS;Health Services;Infectious Diseases;Maternal Health;Microbiome;Pediatric;Pediatric - AIDS;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Sexually Transmitted Infections;Women's Health Research

PHR: PROJECT NARRATIVE This effectiveness trial will increase understanding of the value and cost-effectiveness of diagnostic screening for sexually transmitted infections (STIs) among pregnant women in low and middle-income countries, to reduce adverse pregnancy and infant outcomes. Further, results from this study will provide important data on the role of the vaginal microbiome in Chlamydia trachomatis (CT) testing outcomes and further rationale for studying the vaginal microbiome in pregnant women with CT treatment failure. Together, findings from this R01 are likely to inform changes to STI screening and treatment guidelines in low-middle income countries globally.

PI_NAMEs: KLAUSNER, JEFFREY DAVID (contact);MEDINA-MARINO, ANDREW

PROGRAM_OFFICER_NAME: CHUANG, ELEANORE JENNIFER

PROJECT_TERMS: acceptability and feasibility;adverse birth outcomes;adverse pregnancy outcome;Aftercare;Agreement;Algorithms;antenatal care;arm;Bacteria;Bacterial Vaginosis;Biological Factors;Birth;care systems;case control;Chlamydia Infections;Chlamydia trachomatis;chronic infection;Clinic;Clinical Research;Collaborations;Communities;congenital infection;cost;Cost Analysis;cost comparison;cost effective;cost effectiveness;cost estimate;Data;diagnostic screening;Diagnostic tests;disability-adjusted life years;effectiveness trial;Enrollment;experience;follow-up;Frequencies;Guidelines;HIV;HIV Infections;HIV Seropositivity;Hybrids;In Vitro;Incidence;infant outcome;Infection;innovation;Institution;Intervention;Lactobacillus;low and middle-income countries;Low Birth Weight Infant;male;Metronidazole;Modeling;Molecular;Mother-to-child HIV transmission;National Institute of Child Health and Human Development;Neisseria gonorrhoeae;neonate;Newborn Infant;novel;Outcome;Outcome Study;Perinatal mortality demographics;Play;point of care;Pregnancy;Pregnant Women;Premature Birth;Premature Labor;preterm premature rupture of membranes;Prevalence;prevent;Randomized;Research;Research Personnel;Resources;response;Risk;Role;screening;screening guidelines;Sexually Transmitted Diseases;Signs and Symptoms;Site;South Africa;South African;Specimen;standard of care;Testing;Time;treatment duration;Treatment Failure;treatment guidelines;Treatment outcome;Trichomonas vaginalis;Update;Vagina;vaginal microbiome;vaginal microbiota;Visit;Woman;Women's study;Work

PROJECT_TITLE: Clinical Study of STI Screening to Prevent Adverse Birth and Newborn Outcomes

STUDY_SECTION: IRAP

STUDY_SECTION_NAME: Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section[IRAP]


ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: PROJECT NARRATIVE Interleukin-2 is an immune hormone that regulates immunity to infection, but also influences the development of inflammatory disorders. Human genetic variation at IL2 and its receptor IL2RA is associated with loss of self- tolerance and increased susceptibility to autoimmune disease. However, these polymorphisms are not in the genes themselves, but are located kilobases away in non-coding DNA. We hypothesize that the function disease- associated variants lie within key gene regulatory regions, and the studies proposed in this application will use state-of-the-art 3D epigenomics and CRISPR/Cas9 genome editing to solve the mystery of how non-coding variation influences IL-2-dependent immune functions, and may suggest new ways that tolerance can be restored, and inflammatory disorders can be treated or avoided.

PI_NAMEs: CAMPBELL, DANIEL J;WELLS, ANDREW D (contact)

PROJECT_TERMS: 3-Dimensional;Affinity;Alleles;Animals;Antibodies;Architecture;ATAC-seq;Autoimmune;Autoimmune Diseases;Autoimmune Process;autoinflammatory diseases;B-Lymphocytes;biobank;CD8-Positive T-Lymphocytes;Chromatin;Clinical;Complex;CRISPR/Cas technology;cytokine;Cytokine Receptors;design;Development;Disease;Disease susceptibility;disorder risk;Distant;DNA;Dose;Elements;Engineering;Enhancers;Epigenetic Process;epigenomics;Equilibrium;Extrinsic asthma;Gene Expression;Genes;Genetic;genetic association;Genetic Enhancer Element;Genetic Polymorphism;Genetic Transcription;genetic variant;Genetic Variation;genome editing;genome wide association study;genome-wide;Genomics;Graft Rejection;Homeostasis;Hormones;Human;human disease;Human Genetics;human subject;IL2 gene;IL2RA gene;Immune;immune function;Immune response;Immune Tolerance;Immunity;in vivo;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;insight;Insulin-Dependent Diabetes Mellitus;Intercistronic Region;Interleukin 2 Receptor;Interleukin-2;isoimmunity;Knowledge;Link;Maps;Measures;Mediating;Modeling;Molecular;Mus;novel;novel therapeutic intervention;Nucleic Acid Regulatory Sequences;organ transplant rejection;pathogen;Population;Predisposition;Process;promoter;receptor;Recombinants;Regulatory Element;Regulatory T-Lymphocyte;Reporter;Research Institute;response;risk variant;Role;Self Tolerance;Single Nucleotide Polymorphism;SNP genotyping;Surveys;System;Systemic Lupus Erythematosus;T cell differentiation;T cell response;T-Cell Activation;T-Lymphocyte;Testing;tool;trait;Untranslated RNA;Validation;Variant

PROJECT_TITLE: Mechanisms of autoimmune disease risk in IL2/IL2RA-dependent immune tolerance

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


NIH_SPENDING_CATS: Clinical Research;Genetics;Regenerative Medicine;Wound Healing and Care

ORG_CITY: New York

ORG_NAME: HOSPITAL FOR SPECIAL SURGERY

PHR: Macrophages are immune cells that play important roles in defense against infections, inflammation, and repair of injured tissues. The long term goals of this project are to understand how macrophages are regulated to balance inflammatory and reparative functions to promote tissue repair and restore tissue integrity. This project will investigate communication between inflammatory and reparative pathways and injury-associated macrophage subtypes to gain knowledge that can be used to modulate the immune system to promote tissue repair and wound healing.

PI_NAMEs: IVASHKIV, LIONEL B (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Acceleration;Anatomy;angiogenesis;Anti-Inflammatory Agents;Cells;Cholesterol;Chromatin;Chronic;chronic wound;Cicatrix;Communication;Cues;cytokine;Cytometry;Data;diabetic ulcer;dimensional analysis;Disease;Embryo;Epigenetic Process;Epithelial Cells;Equilibrium;Fatty Acids;Fetal Liver;Fibrosis;Gene Expression Profile;Genes;Genetic Transcription;Glucocorticoids;Goals;Growth;Growth Factor;high dimensionality;Homeostasis;Host Defense;Human;Immune;Immune system;Immunity;immunoregulation;improved;in vivo;Infection;Inflammation;Inflammatory;Inflammatory Response;Injury;injury and repair;insight;Interferon Type II;Interleukin-1;Interleukin-10;Interleukin-13;Interleukin-4;Knowledge;Ligands;Macrophage;microbial products;Modeling;Molecular;monocyte;mouse model;Myelogenous;neutrophil;novel;novel therapeutic intervention;Outcome;Pathologic;Pathology;Pathway interactions;pharmacologic;Phase;Phenotype;Physiological;Platelet-Derived Growth Factor;Play;Population;Production;Proliferating;Regulation;repair function;repaired;Resolution;response;response to injury;Rheumatoid Arthritis;Role;Signal Induction;Signal Pathway;Signal Transduction;single-cell RNA sequencing;STAT3 gene;Stress;Stromal Cells;synergism;Testing;Therapeutic;tissue repair;Tissues;TNF gene;transcription factor;Vascular Endothelial Growth Factors;wound;wound healing;Wound models;Yolk Sac

PROJECT_TITLE: Inhibition of STAT3 and inflammatory cytokine production

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


NIH_SPENDING_CATS: Aging;Biotechnology;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Neurodegenerative;Neurosciences;Parkinson's Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

ORG_CITY: BELMONT

ORG_NAME: MCLEAN HOSPITAL

PHR: Project Narrative: Parkinson’s disease lacks a therapy that could restore dopaminergic neurons permanently lost to the disease process. With a completed development of all steps required for initiating IND-enabling studies, this U01 project in the CREATE Bio Development Track program will accomplish the first cell therapy clinical trials with cGMP frozen autologous midbrain dopaminergic neurons to restore function in patients with Parkinson’s disease. The results from this U01 project will provide necessary information about the safety and feasibility of autologous cell therapy for Parkinson’s disease.

PI_NAMEs: COOPER, OLIVER ;HALLETT, PENELOPE JANE (contact);ISACSON, OLE ;SCHUMACHER, JAMES M

PROGRAM_OFFICER_NAME: BOSHOFF, CHRIS

PROJECT_TERMS: Address;Affect;Agreement;Allogenic;Autologous;Autologous Transplantation;Biodistribution;Biological Assay;Blood;Boston;Bradykinesia;Brain;Cell Line;cell preparation;cell replacement therapy;Cell Therapy;Cell Transplantation;Cells;Chronic;Clinic;Clinical;clinical practice;Clinical Research;Clinical Trials;Core Facility;Corpus striatum structure;Cryopreservation;Cyclic GMP;Dana-Farber Cancer Institute;Deep Brain Stimulation;Development;Devices;Diagnosis;Disease;disease model;Dopamine;Dopaminergic Cell;dopaminergic neuron;Enrollment;Excipients;experimental study;Family;fetal;fetus cell;first-in-human;Freezing;functional restoration;Future;Generations;Guidelines;Hospitals;Human;human induced pluripotent stem cells;immunodeficiency;Immunodeficient Mouse;Immunosuppression;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;innovation;Intervention;L-DOPA induced dyskinesia;Medical;Medical Care Costs;Midbrain structure;Motor;motor function improvement;motor symptom;National Institute of Neurological Disorders and Stroke;nerve supply;Nervous System Disorder;Neurologic;nonhuman primate;open label;Parkinson Disease;Parkinsonian Disorders;patient derived induced pluripotent stem cells;patient population;Patient Recruitments;Patients;Phase;Phase I Clinical Trials;pluripotent stem cell differentiation;posture instability;pre-Investigational New Drug meeting;Preparation;Procedures;Process;programs;Published Comment;putamen;Qualifying;Quality Control;Rattus;Reagent;repaired;Research Personnel;Rodent;Safety;safety and feasibility;safety testing;side effect;Somatic Cell;Source;sporadic Parkinson's Disease;Symptoms;Synapses;Technology;Testing;Therapeutic;Therapy Clinical Trials;Time;Transplant Recipients;Transplantation;Tremor;Tumorigenicity;Woman;Work

PROJECT_TITLE: Parkinsons Disease Scalable iPSC Autologous Cell Therapy

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders B Study Section[NSD-B]


NIH_SPENDING_CATS: Bioengineering;Lung;Machine Learning and Artificial Intelligence;Orphan Drug;Pulmonary Fibrosis;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: LOS ANGELES

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative We have developed a 3D bioengineered model of human Idiopathic Pulmonary Fibrosis. We aim to further develop, improve and validate this model as a clinically relevant model for Idiopathic Pulmonary Fibrosis. The overall goal is to develop this model for drug screening to find new therapies for this terrible lung disease.

PI_NAMEs: BELPERIO, JOHN A;DAMOISEAUX, ROBERT ;GOMPERTS, BRIGITTE N (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: 3-Dimensional;Affect;Age;age related changes;airway epithelium;Algorithmic Analysis;Alveolar;analysis pipeline;Animal Model;antifibrotic treatment;Apoptosis;Architecture;Biological Assay;Biological Models;Biological Process;Biology;Biomedical Engineering;CASP3 gene;Cell Aging;Cell Differentiation process;Cell Line;cell type;Cells;Characteristics;chemokine;Chronic;clinically relevant;Collection;curative treatments;cytokine;Data;deep learning;Disease;disease model;drug discovery;Drug Modelings;Drug Screening;drug use screening;efficacy study;Epithelial Cells;Epithelium;Ethnic Origin;Etiology;Extracellular Matrix;Fibroblasts;Fibrosis;fibrotic lung;Gender;genetic risk factor;genetic variant;Goals;Health;Heterogeneity;high-throughput drug screening;Host Defense;Human;human induced pluripotent stem cells;human model;idiopathic pulmonary fibrosis;Image;Image Analysis;image processing;improved;in vitro Model;induced pluripotent stem cell;Inflammatory;innovation;International;Interstitial Lung Diseases;Lung;Lung Diseases;machine learning algorithm;Measures;Mesenchymal;Methods;Michigan;Modeling;Molecular;MUC5B gene;novel therapeutics;Pathogenesis;Pathologist;patient derived induced pluripotent stem cells;Patients;Phenocopy;Phenotype;precision medicine;prevent;Race;Reporter;Reporting;Research;Research Personnel;RNA analysis;Running;senescence;senescence associated secretory phenotype;Signal Transduction;single-cell RNA sequencing;small molecule;Standardization;stem cell model;Structure of parenchyma of lung;success;System;Techniques;three-dimensional modeling;Tissues;Validation

PROJECT_TITLE: Validation of an in vitro model of progressive fibrosis that mimics Idiopathic Pulmonary Fibrosis


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Microbiome

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE C. Difficile infection is common in patients undergoing antibiotic treatment and might have severe health consequences, including death. Here we propose to leverage on our recent findings that bacteria-derived metabolites, such as acetate, may decrease severity of C. difficile infection. Our goal is to mechanistically understand how good intestinal bacteria and their metabolites harness immune responses in the gut to contain C. difficile growth.

PI_NAMEs: COLONNA, MARCO  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: 16S ribosomal RNA sequencing;Acetates;Address;anti-microbial peptide;Antibiotic Therapy;antimicrobial;Bacteria;Binding Proteins;Biological Availability;Brazil;Cell Surface Receptors;cell type;Cessation of life;Chemotactic Factors;Clostridium difficile;cohort;Colectomy;Collaborations;Data;Diarrhea;dysbiosis;Epithelial Cells;experimental study;fecal transplantation;FFAR2 gene;forging;fundamental research;Gene Expression Profile;Genetic Transcription;Germ-Free;Goals;Growth;gut microbiota;Health;high risk;Hospitalization;Host Defense;Human;Immune response;In Vitro;in vivo;Incidence;Infection;Infection prevention;Inflammasome;innovation;Interleukin-1 beta;interleukin-22;intestinal epithelium;Intestines;Joints;Laboratories;Lymphoid;Lymphoid Cell;Mediating;Metabolism;metabolomics;microbial;microbiota;mortality;Mucosal Immune Responses;Mucous Membrane;Mus;Natural Immunity;neutrophil;Neutrophil Activation;Neutrophil Infiltration;novel;Organogenesis;Patients;Play;Production;Productivity;protective effect;Protein Deficiency;Pseudomembranous Colitis;receptor;Recurrence;Regulation;Resistance;response;Role;Secure;Severities;Signal Transduction;Surface;synergism;Testing;Therapeutic;Therapeutic Intervention;Time;Toxic Megacolon;Toxin;transcriptome;Translating;translational potential;Treatment Failure;Volatile Fatty Acids;Work

PROJECT_TITLE: MICROBIOTA-DEPENDENT CONTROL OF CLOSTRIDIUM DIFFICILE: THE ROLE OF ACETATE AND IL-22 BINDING PROTEIN


ORG_CITY: SAN FRANCISCO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative: Our program of research uses molecular, genetic, neuroanatomical, cellular imaging and behavioral approaches to provide a comprehensive analysis of the circuits that transmit pain and itch messages to the brain. This program will provide a more complete picture of the extent to which pain and itch circuits remain independent or interact throughout the neuroaxis and we will continue to develop revolutionary cell transplantation approaches to the management of chronic pain and itch. \

PI_NAMEs: BASBAUM, ALLAN I. (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Ablation;Afferent Neurons;animal pain;awake;Behavioral;Behavioral Paradigm;Brain;Cell Transplantation;cellular imaging;chronic itch;chronic pain;chronic pain management;designer receptors exclusively activated by designer drugs;Development;Electrophysiology (science);experience;experimental study;Genetic;Heterogeneity;Human;Image;Imaging Techniques;Injury;innovation;insight;Interneurons;Knowledge;Mechanics;Mediating;Molecular;molecular subtypes;mouse model;multidisciplinary;Mus;Neuroanatomy;Neurology;Neurons;novel;novel strategies;Pain;pain perception;Pain quality;Population;Process;programs;Property;Pruritus;Rabies;Research;response;segregation;Signal Transduction;Simplexvirus;Spinal Cord;Stimulus;Time;transmission process;Validation;Viral

PROJECT_TITLE: From the spinal cord to the brain: Neurology of the pain and itch neurons


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

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE: While cognitive impairment is the major manifestation of Alzheimer’s disease (AD), the leading cause of dementia in the elderly, unintentional body weight loss from unclear reasons often precedes the mental decline and can result in faster progression of the disease. The present application seeks to explore the novel hypothesis that brain regions regulating body weight and metabolism, including the hypothalamus, are selectively vulnerable at the early stages of AD. The proposed research is relevant to public health because understanding the underlying mechanisms for the early weight loss and metabolic dysfunction may suggest new therapies for this currently incurable disease with no effective treatments.

PI_NAMEs: ISHII, MAKOTO  (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: abeta accumulation;Acceleration;Adipocytes;Affect;Aging;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease related dementia;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Atrophic;Attention;Award;base;bench to bedside;beta amyloid pathology;Body Weight;Body Weight decreased;Brain;Brain region;cell type;Cells;Cerebrospinal Fluid;Clinical;clinically relevant;Cognition;Cognitive;cognitive change;Cognitive deficits;cohort;comparison control;Cre lox recombination system;Data;Dementia;Diagnostic;Disease;Disease Progression;Early identification;effective therapy;Elderly;Event;experimental study;Failure;Functional disorder;Genetic;Genomic approach;Goals;Homeostasis;Hormones;Human;human subject;Huntington Disease;Hypothalamic dysfunction;Hypothalamic structure;imaging approach;Impaired cognition;improved;in vivo;Individual;insight;Intervention Trial;Knock-out;Knowledge;Leptin;Longitudinal Studies;Medical Research;Memory impairment;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolism;Molecular;mortality;mouse model;neural network;neuron loss;Neuronal Dysfunction;Neurons;neuropeptide Y;neurophysiology;novel;novel therapeutics;Outcome Study;Pathogenesis;Pathologic;Pathway interactions;Peptides;Plasma;Population;pre-clinical;prospective;Psyche structure;Public Health;Research;Research Institute;Role;Senile Plaques;Signal Pathway;Signal Transduction;Signaling Molecule;Synapses;Testing;Tg2576;Therapeutic;Transgenic Mice;Universities;Washington;Weight Gain

PROJECT_TITLE: Hypothalamic and metabolic dysfunction in Alzheimer's disease


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

ORG_CITY: LUBBOCK

ORG_NAME: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER

PHR: PUBLIC HEALTH RELEVANCE STATEMENT (PROJECT NARRATIVE) There is growing evidence that pathological accumulation of toxic reactive oxygen species (ROS) is an early event in the hippocampal dentate gyrus (DG) of patients with Alzheimer’s disease. This proposal tests the hypothesis that depletion of the antioxidant all-trans retinoic acid (ATRA) in the DG promotes ROS toxicity, mitochondrial dysfunction, and transcriptional dysregulation of ATRA-sensitive genes. Combining novel AD mouse model crosses, single cell transcriptomics, and electrophysiology, this proposal investigates roles of RA in preserving DG-specific learning, DG circuit function, and transcription of RA-sensitive genes across DG cell types.

PI_NAMEs: LAWRENCE, JOHN JOSHUA (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Acceleration;age related;age related decline;Aging;Agonist;All-Trans-Retinol;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer’s disease biomarker;Amyloidosis;Antioxidants;Autopsy;Behavior;Behavioral;bench to bedside;Biological Markers;Brain;cell type;Cells;Chronic;Data;dentate gyrus;dietary;dietary manipulation;DNA;Electrophysiology (science);Event;Experimental Designs;Free Radicals;Functional disorder;Gene Expression;Genes;Genetic Transcription;granule cell;Hippocampus;Human;human model;Impaired cognition;Impairment;inhibitory neuron;innovation;Intake;interdisciplinary approach;Interneurons;J20 mouse;Knowledge;LacZ Genes;Learning;Lipids;Liver;Measures;Membrane;Memory;Memory impairment;Mitochondria;mitochondrial dysfunction;Molecular;mouse model;Mus;Neuroglia;Neurons;novel;Outcome Measure;oxidative damage;Oxidative Stress;Oxidative Stress Induction;Pathogenesis;Pathologic;Pathway interactions;Performance;Play;preservation;prevent;Process;Production;Property;protective effect;Proteins;public health relevance;Reactive Oxygen Species;Reporter;Retinoic Acid Receptor;Reversal Learning;Rodent;Role;secondary analysis;Signal Transduction;Supplementation;Synapses;synaptic function;Testing;theories;Toxic effect;Transcript;Transcriptional Regulation;transcriptomics;Tretinoin;Up-Regulation;Vitamin A Deficiency

PROJECT_TITLE: Transcriptional Dysfunction in Dentate Gyrus Cell Types: Roles of Retinoic Acid Responsive Genes in Protection Against Alzheimer's Disease Pathogenesis

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project Narrative Cytomegalovirus (CMV) can cause serious health problems and life-threatening disease in newborns and immunosuppressed individuals (including cancer and transplant patients). This proposal seeks to understand the transcriptional mechanisms underlying natural killer (NK) cell metabolism in host immunity against CMV infection. Defining the molecular mechanisms by which NK cells respond to pathogens will potentially lead to therapeutic benefits.

PI_NAMEs: SUN, JOSEPH CHAI-YUEN (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Ablation;Activated Natural Killer Cell;adaptive immunity;aerobic glycolysis;Anti-viral Response;arm;ATAC-seq;Binding;Biological Assay;Biology;Cancer Patient;Carnitine Palmitoyltransferase I;Cell Compartmentation;Cell Separation;Cells;Cellular Metabolic Process;Chemicals;ChIP-seq;Chromatin;Clonal Expansion;Communicable Diseases;Competence;Critical Pathways;cytokine;Cytomegalovirus;Cytomegalovirus Infections;Data;Deposition;detection platform;Disease;Effector Cell;Engineering;Enzymes;Epigenetic Process;epigenomics;Exhibits;experimental study;Exposure to;extracellular;Family;fatty acid oxidation;Fatty Acids;fighting;Flow Cytometry;Generations;Genes;Genetic Transcription;Genus Hippocampus;Glycolysis;Goals;Grant;Health;Histones;Host Defense;Human;Immune;Immunity;Immunization;Immunologic Memory;immunosuppressed;In Vitro;in vivo;Individual;Infection;Inflammatory;inhibitor;Innate Immune System;Invaded;Laboratories;lactate dehydrogenase A;Life;Lymphocyte;Mass Spectrum Analysis;Measures;Mediating;Memory;Metabolic;metabolic abnormality assessment;Metabolic Pathway;Metabolism;metabolomics;Mitochondria;mitochondrial fitness;mitochondrial metabolism;Modeling;Molecular;mouse model;Murid herpesvirus 1;Mus;Natural Killer Cells;Newborn Infant;NK Cell Activation;novel;oxidation;Oxygen Consumption;pathogen;Pathway interactions;Patients;permissiveness;Play;Predisposition;Proliferating;Promoter Regions;Regulation;Reporter;Research;response;Rest;RNA;RNA analysis;Role;STAT4 gene;Therapeutic;transcription factor;Transcriptional Regulation;transcriptome sequencing;transcriptomics;Transgenic Mice;Transplant Recipients;Up-Regulation;Viral;Virus;Virus Diseases

PROJECT_TITLE: Transcriptional control of NK cell metabolism

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


NIH_SPENDING_CATS: Asthma;Breastfeeding, Lactation and Breast Milk;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Indoor Air Pollution;Lung;Pediatric;Prevention

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative Allergic asthma is a chronic inflammatory lung disease, initiated during childhood and directed by T helper type 2 (Th2) cells. The "hygiene hypothesis" proposes that the decreased exposure to dust containing high levels of bacterial endotoxin (LPS) at a very early age increases the incidence of asthma in children, and we have found that this is most likely explained by a natural LPS hyporesponsiveness during infancy. This proposal will determine how natural maternal-interactions and environmental exposure to microbial products can influence the development of allergen-specific Th2 cells and therefore, asthma severity from early infancy.

PI_NAMEs: LUND, FRANCES E. (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Adult;Adult asthma;Affect;Age;airborne allergen;Allergens;Allergic;allergic airway inflammation;Allergic inflammation;allergic response;Asthma;asthma prevention;Breast Feeding;Cell Communication;Cell Differentiation process;Cells;Child;Childhood;Childhood Asthma;Chronic;chronic inflammatory lung disease;Chronic lung disease;Clinical Data;cost;cytokine;Data;Dendritic Cells;Developed Countries;Development;Diet;Disease;Dose;Dust;early childhood;Economic Burden;Endotoxins;Environment;Environmental Exposure;experience;experimental study;Exposure to;Extrinsic asthma;Farm;Formulation;Genes;Genetic;Genetic Transcription;Helper-Inducer T-Lymphocyte;high risk;Human Milk;Hygiene;Hypersensitivity;IL18 gene;Impairment;Incidence;infancy;Infant;Inflammation;Inflammatory Response;interest;Interferon Type II;Interleukin-12;Interleukin-6;ITGAM gene;Lactation;Licensing;Life;Life Style;Mediating;Mediator;Microbe;microbial;microbial products;microorganism;milk supply;monocyte;Morbidity - disease rate;mortality;Mus;Outcome;Pathogenesis;Persons;Play;Predisposition;Prevalence;prevent;Prevention;Prevention approach;Process;Production;programs;Public Health;Publishing;Relapse;response;Risk;Risk Factors;Risk Reduction;Role;rural area;Severities;Signal Transduction;Source;Symptoms;T cell regulation;T cell response;T-Cell Activation;T-Lymphocyte;Testing;Th2 Cells;TNF gene;Up-Regulation;urban area;Work

PROJECT_TITLE: Regulation of T cell responses to allergens and environmental microbes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-T(57)]


PHR: PROJECT NARRATIVE Despite effective anti-retroviral therapy in HIV-infected patients, proviruses persist in a transcriptionally silent, latent state in resting lymphocytes and cells from the central nervous system. Identifying the most effective and selective therapeutic routes to eliminate the latent reservoir requires a comprehensive understanding of the molecular rules normally controlling proviral transcription and how their dysfunction promotes latency establishment and maintenance. In this proposal, we will investigate a previously unexplored host co-factor that is critical for promoting the latency-reactivation switch in response to physiologic immune cell signaling to devise rationale approaches for targeting unique druggable pockets to translate the basic discoveries for pre- clinical applications.

PI_NAMEs: D'ORSO, IVAN  (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, DIANE M

PROJECT_TERMS: Achievement;antiretroviral therapy;Applications Grants;Architecture;Attention;bench to bedside;Binding;Biology;Biomedical Research;C-terminal;CD4 Positive T Lymphocytes;cell type;Cells;Central Nervous System;Chromatin;Clinical;clinically relevant;Clonal Expansion;cofactor;Communication;Complex;Cues;Data;Epidemic;Exposure to;Feedback;Functional disorder;genetic corepressor;Genetic Transcription;Genome;Goals;Heterogeneity;Histone Acetylation;Histone Code;HIV;HIV Infections;Immune;Immune signaling;Immunologic Stimulation;In Vitro;Infection;innovation;Integration Host Factors;Intervention;Knowledge;Lymphocyte;Maintenance;Mediating;Mission;Modeling;Molecular;Molecular Probes;multicatalytic endopeptidase complex;N-terminal;National Institute of Allergy and Infectious Disease;new technology;novel;novel strategies;Outcome;Output;Patients;Phase;Physiological;pre-clinical;programs;promoter;Proviruses;Publishing;reactivation from latency;Reader;Repression;response;Rest;Role;Route;Sampling;scaffold;Shapes;Signal Transduction;System;targeted treatment;Testing;Therapeutic;therapeutic target;Tissues;Transcription Elongation;Transcription Initiation;Transcriptional Activation;Transcriptional Regulation;Translating;Ubiquitin C;ubiquitin-protein ligase;Ubiquitination;Viral;Virus Replication;Work

PROJECT_TITLE: Transcriptional regulatory mechanisms shaping HIV proviral fate

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Digestive Diseases;Genetics

ORG_CITY: STORRS-MANSFIELD

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

ORG_STATE: CT

PHR: Project Narrative The proposed work will elucidate the epigenetic regulatory mechanisms by long noncoding RNAs (lncRNAs) that control homeostasis of drug-metabolizing P450 (CYP) enzymes in a positive and negative feedback loop after exposure to drugs. The proposed work will determine the roles of lncRNAs in CYP-mediated drug metabolism and susceptibility to drug induced liver injury (DILI). The generated knowledge will help to identify novel key factors for predicting therapeutic efficacy and adverse drug reactions (ADRs).

PI_NAMEs: ZHONG, XIAO-BO  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Address;adverse drug reaction;Binding;chromosomal location;constitutive androstane receptor;Cytochrome P450;drug induced liver injury;drug metabolism;Enzymes;Epigenetic Process;Exposure to;Feedback;Gene Expression;Gene Expression Regulation;Genes;hepatocyte nuclear factor;histone modification;HNF4A gene;Homeostasis;In Vitro;in vivo Model;Knowledge;Liver;Liver Regeneration;Mediating;Molecular;novel;outcome prediction;Pharmaceutical Preparations;Pharmacotherapy;Positioning Attribute;Predictive Factor;Predisposition;pregnane X receptor;Process;Regulation;Repression;Response Elements;Role;therapy outcome;transcription factor;Transcriptional Regulation;Treatment Efficacy;Untranslated RNA;Work

PROJECT_TITLE: The role of lncRNAs in P450-mediated drug metabolism and drug-induced liver injury

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


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Burden of Illness;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Lung;Pediatric;Prevention;Rare Diseases;Tuberculosis

ORG_CITY: Stellenbosch

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: STELLENBOSCH UNIVERSITY

PHR: PROJECT NARRATIVE Despite tuberculosis (TB) being a treatable and preventable disease, recent modeling work estimated that nearly 200,000 children <5 years died of TB during 2015, making it one of the top ten causes of death in children under 5 years globally. Unreliable and incomplete surveillance data for children with TB is a key challenge that currently limits our ability to appropriately manage children with this disease, including those suffering from severe forms such as TB meningitis (TBM) who experiences high mortality and often lifelong disability. This project will use interdisciplinary methods, including modelling and spatial analyses, to provide critical information on the burden, incidence and related mortality of TBM in children at a global, national and sub-national level in South Africa, whilst identifying opportunities to improve prevention and care through in- depth prospective surveillance.

PI_NAMEs: DU PREEZ, KAREN  (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Adult;age related;analytical method;attributable mortality;Autopsy;burden of illness;career;career development;Caring;Case Fatality Rates;Cause of Death;Cessation of life;chemotherapy;Child;Child health care;Childhood;Clinic;Clinical;Community Health Services;comorbidity;Country;Data;Databases;Dedications;demographics;Detection;Development;Diagnosis;Diagnostic;diagnostic algorithm;Disease;Disease Management;Disease Outcome;Disease Progression;disorder risk;Drug resistance in tuberculosis;Early Diagnosis;Early treatment;Economics;effective therapy;Eligibility Determination;experience;Family;family burden;Future;Geography;Goals;Health;Health Services;Heterogeneity;high risk;HIV;Hospitals;improved;Incidence;Individual;Infection;International;Intervention;Laboratories;Leadership;Lifelong disability;Literature;Location;low and middle-income countries;mathematical model;Meningeal Tuberculosis;Mentors;Methods;Modeling;Morbidity - disease rate;mortality;multiple data sources;Mycobacterium tuberculosis;Neurological disability;Neurological outcome;novel;observational cohort study;Outcome;Pharmaceutical Preparations;Pharmacy facility;Policies;Population;Predisposition;Prevalence;prevent;Prevention;Preventive therapy;Program Evaluation;programs;prospective;public health priorities;public health research;Records;Reporting;Research;Research Personnel;Research Support;Resource-limited setting;Risk;Scientist;Severity of illness;skills;social;South Africa;South African;spatiotemporal;support network;surveillance data;surveillance strategy;Symptoms;System;Techniques;Training;Translating;Treatment outcome;Tuberculosis;Tuberculosis diagnosis;tuberculosis treatment;United States Public Health Service;Universities;Work;World Health Organization

PROJECT_TITLE: Interdisciplinary and multi-level approach to estimate the disease burden and outcomes of childhood tuberculous meningitis.

STUDY_SECTION_NAME: International and Cooperative Projects - 1 Study Section[ICP1]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Neurosciences;Nutrition;Obesity

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: PROJECT NARRATIVE Obesity, the leading cause of morbidity and mortality worldwide, is characterized by hypothalamic resistance to the anorexigenic hormone leptin, produced by fat cells, and loss of the satiety hormone uroguanylin, produced by intestinal cells. Receptors for these hormones, leptin receptor and guanylyl cyclase c (GUCY2C), respectively, are uniquely co-expressed by neurons in the hypothalamic ventral premamillary nucleus (PMV), suggesting their function may be linked. Here, we will determine if loss of uroguanylin-GUCY2C signaling in the hypothalamus underlies leptin resistance in obesity and if this resistance, and the associated loss of appetite control, can be reversed using clinically available GUCY2C agonists.

PI_NAMEs: BARTON, JOSHUA R (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Acceleration;Adipocytes;Adipose tissue;Adult;Agonist;Animals;appetite loss;Appetite Regulation;Attenuated;Binding;Biochemical;Body Weight decreased;Cell membrane;Cell Nucleus;Cell surface;Cell Surface Proteins;Cells;Cessation of life;Chronic;Circulation;Clinical;Constipation;Cyclic GMP;Data;desensitization;Desire for food;diet-induced obesity;Disease;Down-Regulation;enterotoxin receptor;Exhibits;Fatty acid glycerol esters;feeding;Genetic;Goals;gut-brain axis;Health Expenditures;Hormone Receptor;Hormone secretion;Hormones;Hyperphagia;Hypothalamic structure;In Vitro;ineffective therapies;insight;Intestines;Laboratories;Leptin;leptin receptor;Leptin resistance;Ligands;Link;Measures;Mediating;Metabolic;Metabolism;Methods;Morbidity - disease rate;mortality;mouse model;Mus;Neurons;Neurosecretory Systems;novel;novel therapeutics;Obese Mice;Obesity;obesity prevention;obesity treatment;Outcome;Overweight;pandemic disease;Patients;Peripheral;pharmacologic;Phenotype;Population;receptor;Receptor Signaling;reconstitution;repaired;Reporter;Resistance;response;Safety;Satiation;Signal Transduction;Small Intestines;Supplementation;Surface;Syndrome;Therapeutic;Tissues;Transgenes;Transgenic Organisms;Translating;translational potential;trend;uroguanylin;Weight Gain

PROJECT_TITLE: Silencing the uroguanylin-GUCY2C gut-brain axis mediates leptin resistance in obesity


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Back Pain;Bioengineering;Biotechnology;Chronic Pain;Pain Research;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Narrative  Intervertebral disc degeneration, a cascade of cellular, structural and compositional changes, is strongly implicated as a cause of low back pain. Stem cell-based disc regeneration holds promise for low back pain patients, but efficacy is adversely impacted by the nutrient poor, acidic and inflammatory microenvironment of the degenerate disc. The overall objective of this proposal is to develop a novel biological therapy for disc degeneration that maximizes the survival and anabolic potential of therapeutic stem cells by simultaneously neutralizing the degenerate disc microenvironment via the sustained delivery of nutrients, anti-inflammatory drugs and buffering agents.

PI_NAMEs: MALHOTRA, NEIL ;MAUCK, ROBERT L;SMITH, LACHLAN JAMES (contact)

PROGRAM_OFFICER_NAME: MARQUITZ, ARON

PROJECT_TERMS: Address;Adopted;Animal Model;Anti-Inflammatory Agents;Biological Assay;Biological Response Modifier Therapy;Biomechanics;Buffers;Cell Physiology;Cells;Characteristics;Chondroitin ABC Lyase;Clinical;clinical application;Clinical Trials;clinically relevant;Coupled;cytokine;design;disability;disc regeneration;Dose;Drug Delivery Systems;economic cost;Failure;Functional Regeneration;Glucose;Goals;Goat;Human;Human Characteristics;implantation;improved;In Situ;In Vitro;in vivo;Inflammation;Inflammation Mediators;Inflammatory;Injections;Intervertebral disc structure;intervertebral disk degeneration;Long-Term Potentiation;Longitudinal Studies;Low Back Pain;Measures;Mechanics;Mediating;Mesenchymal Stem Cells;Methods;Microcapsules drug delivery system;Modeling;novel;novel therapeutics;nucleus pulposus;Nutrient;nutrition;Oxygen;Pain Measurement;pain patient;pain symptom;Performance;Pharmaceutical Preparations;Phenotype;Physiologic Monitoring;Physiological;Positioning Attribute;pre-clinical;preclinical efficacy;quantitative imaging;regeneration potential;Reproducibility;restoration;Safety;Series;Severities;socioeconomics;stem cell survival;stem cell therapy;stem cells;Structure;symptom management;Symptoms;System;Therapeutic;Therapeutic Intervention;Time;Tissues;tool;Treatment Efficacy;United States

PROJECT_TITLE: Neutralizing the degenerate disc microenvironment to enhance the efficacy of therapeutic stem cells


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Infectious Diseases;Prevention;Primary Immunodeficiencies;Rare Diseases;Sexually Transmitted Infections

ORG_DEPT: GENETICS

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative EV is a group of AR inborn errors of cutaneous immunity that underlie persistent and disseminated skin lesions caused by defective yet oncogenic β-HPVs. Despite the identification of several genetic etiologies, suggesting that keratinocytes and T cells jointly contribute to protective immunity against β-HPVs, the molecular and cellular basis of EV remains largely unknown. We will search for novel genetic etiologies of EV, attempt to connect them with known etiologies, and analyze the molecular and cellular mechanisms by which these disorders underlie β- HPVs-driven skin lesions.

PI_NAMEs: CASANOVA, JEAN-LAURENT  (contact);JOUANGUY, EMMANUELLE

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: adaptive immunity;Affect;Alleles;Area;autosome;Binding;Cell Line;Cells;Clinical;Communicable Diseases;Complex;congenital immunodeficiency;CRISPR/Cas technology;Cutaneous;Data;Development;diagnostic strategy;Differentiation and Growth;Disease;Enrollment;Epidermodysplasia Verruciformis;Epithelial Cells;Etiology;exome;exome sequencing;Family;General Population;Genes;Genetic Counseling;Genetic Predisposition to Disease;Genetic study;genome sequencing;genome-wide;genome-wide linkage;Genotype;Goals;Growth;Hematology;Hematopoietic Stem Cell Transplantation;Hereditary Disease;Human;Human Herpesvirus 8;human model;Human papilloma virus infection;Human Papillomavirus;IL2RG gene;Immunity;Immunologics;improved;In Vitro;Individual;Infection;innovation;insight;Interferons;ITGAL gene;ITGB2 gene;JAK3 gene;Kaposi Sarcoma;keratinocyte;kindred;Lesion;Leukocyte Adhesion Deficiency;Malignant Neoplasms;member;Mendelian disorder;Modeling;Molecular;Molecular Diagnosis;Mucous Membrane;Mus;mutant;Mutate;Mutation;Neutropenia;notch protein;novel;novel diagnostics;novel therapeutic intervention;null mutation;Oncogenic;Oncogenic Viruses;OX40;Papillomavirus;particle;Pathogenesis;Pathogenicity;Pathway interactions;Patients;penis foreskin;permissiveness;Phenotype;Physicians;Predisposition;prevent;Preventive;Proteins;Public Health;recruit;Recurrence;Reporting;Research;RHOH gene;Severe Combined Immunodeficiency;Skin;Skin Cancer;Skin Carcinoma;skin lesion;Sun Exposure;T cell reconstitution;T-Lymphocyte;Therapeutic;tumor;Viral;Viral Proteins;Virulent;Virus;whole genome

PROJECT_TITLE: Molecular and cellular basis of epidermodysplasia verruciformis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IMM-K(52)]


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: CHICAGO

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative: Improving care for women with urinary incontinence (UI) begins by systematically and equitably screening for this common disease and then partnering with patients on shared decision-making regarding treatment options. In this application, we propose a multi-faceted strategy to implement routine screening for UI in women in sixty-five primary care clinics and then use our unique existing partnership with Wisercare©, an established evidenced-based patient education tool, to inform patients on treatment options and expand access to non-surgical UI treatments through the primary care setting. Our initiative should produce a sustainable transformation in UI care and a replicable model for other health systems.

PI_NAMEs: KENTON, KIMBERLY SUE;PERSELL, STEPHEN  (contact)

PROGRAM_OFFICER_NAME: ZHANG, XINZHI

PROJECT_TITLE: Identify, Teach and Treat (IT2): Automating clinical decision pathways for the care of women