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

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Public relevance Emotional well-being is critical for maintaining quality of life and preventing dementia among older adults. A thorough understanding of the brain mechanisms of emotional well-being as well as the relationship between emotional well-being and dementia will form the basis for identification of biomarkers and intervention strategies for promoting positive well-being and preventing dementia among older adults. The proposed network will strengthen the growth of multidisciplinary research and investigators to serve this need.

PI_NAMEs: CONWELL, YEATES  (contact);LIN, FENG VANKEE;WANG, KUAN HONG

PROGRAM_OFFICER_NAME: PLUDE, DANA JEFFREY

PROJECT_TERMS: Address;Adult;Advisory Committees;Aging;aging brain;aging related;Alzheimer's disease related dementia;Animal Model;Animals;Area;Biological Markers;biomarker identification;Brain;brain based;brain health;Brain imaging;brain research;cohort;Cohort Studies;Collaborations;Consultations;Data;Dementia;density;Development;early detection biomarkers;Educational workshop;Emotional;Ensure;Evaluation;Faculty;Funding;Future;Gerontology;Grant;Growth;Health;healthspan;hedonic;Heterogeneity;Human;human model;Interdisciplinary Study;interest;International;Intervention;Learning;Literature;Measurement;Measures;Mediating;meetings;Mental Health;Mentorship;Methods;Modeling;Nature;neuroimaging;neuropathology;Neurosciences;novel;older adult;Outcome;Paper;Pathologic;Peer Review;Personal Satisfaction;Pilot Projects;Population;prevent;Prevention strategy;Process;Productivity;Protocols documentation;Publishing;Quality of life;Regulation;repository;Reproducibility;Research;Research Methodology;Research Personnel;Research Project Grants;resilience;Resources;Risk;Role;Series;Societies;Stress;Testing;therapeutic target;Time;Universities;Update;web site;webinar;Well in self

PROJECT_TITLE: Network For Emotional Wellbeing And Brain Aging (NEW Brain Aging)


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: BALTIMORE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PATHOLOGY

ORG_FIPS: US

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative The proposed research is relevant to public health because it investigates the normal and disease-related functions of tau, a key protein involved in Alzheimer's disease. This research will contribute to our knowledge of mechanisms of sporadic Alzheimer's disease and may lead to new therapeutic strategies to treat this devastating disease. Thus, the proposed research is relevant to the part of the NIH's mission that pertains to seeking knowledge about the behavior of living systems and application of that knowledge to reduce illness and disability.

PI_NAMEs: MORRIS, MEAGHAN O'MALLEY (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: abeta oligomer;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease therapy;AMPA Receptors;Amyloid beta-Protein;Area;Award;Behavior;Binding;Biological Process;Biology;Biometry;career;collaborative environment;Coupled;Data;Development;disability;Disease;fluorescence imaging;Foundations;Future;Goals;Hippocampus;Human;human induced pluripotent stem cells;Imaging Techniques;improved;Induced pluripotent stem cell derived neurons;innovation;insight;Investigation;knock-down;Knock-out;Knockout Mice;Knowledge;Label;Link;Long-Term Depression;MAPT gene;Mass Spectrum Analysis;Mentorship;Mission;Modeling;Molecular;mouse model;Mus;Neurodegenerative Disorders;Neuronal Plasticity;Neurons;neuropathology;new therapeutic target;novel;novel therapeutic intervention;Organism;Outcome;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Pattern;Physicians;postsynaptic;Process;Proteins;Protocols documentation;Public Health;Rattus;Regulation;Research;Resistance;Role;Scientist;Seizures;stem cell model;Synapses;Synaptic plasticity;tau function;tau interaction;tau Proteins;Testing;Therapeutic;therapeutically effective;trafficking;Training;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: The Role of the Tau in Homeostatic Scaling and Mechanisms of Alzheimer's Disease

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Basic Neuroscience of Aging Study Section[NIA-N]


ADMINISTERING_IC: AI

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Cancer;Cervical Cancer;Infectious Diseases;Prevention;Sexually Transmitted Infections;Women's Health Research

ORG_CITY: ANN ARBOR

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Narrative High-risk human papillomaviruses (HPVs) cause essentially all cancers of the uterine cervix, as well as many other anogenital and oropharyngeal cancers. Despite the availability of highly effective prophylactic vaccines against HPV infection, cancers associated with HPV infection remain a major disease burden due to the limited use of the vaccine and the absence of vaccine benefit in people with current HPV infection. As elucidating the cellular basis of HPV infection may reveal valuable new strategies to combat HPV infection, in this proposal we propose to clarify a critical entry step during HPV infection.

PI_NAMEs: DIMAIO, DANIEL C.;TSAI, BILLY  (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Anogenital cancer;Binding;Biochemical;burden of illness;Capsid;Capsid Proteins;Cell Nucleus;Cell Physiology;Cells;Cellular biology;Collaborations;combat;Complex;Cytoplasm;Endocytosis;endosome membrane;Endosomes;Endowment;Event;experimental study;Foundations;gamma secretase;Golgi Apparatus;Golgi Targeting;Grant;high risk;Human;Human papilloma virus infection;Human Papillomavirus;human pathogen;improved;In Vitro;Individual;Infection;Infection prevention;insight;Integral Membrane Protein;Integration Host Factors;intracellular protein transport;L2 viral capsid protein;Malignant neoplasm of cervix uteri;Malignant Neoplasms;malignant oropharynx neoplasm;Mass Spectrum Analysis;Mediating;Membrane;membrane reconstitution;Minor;Molecular;Molecular Chaperones;Molecular Conformation;mutant;Mutation;N-terminal;novel;novel therapeutic intervention;Pathway interactions;Penetration;Peptide Hydrolases;Peptides;Persons;Play;prevent;Preventive vaccine;Process;Productivity;protein complex;Proteins;Proteomics;Publishing;receptor;recruit;Research Personnel;Role;Route;Sorting;Testing;trafficking;trans-Golgi Network;Transmembrane Domain;Uterine Cancer;Vaccines;Viral;Viral Genome;Virion;virology;Virus

PROJECT_TITLE: Mechanism of gamma-secretase action during HPV infection

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Kidney Disease;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn

ORG_CITY: NEW YORK

ORG_DEPT: PEDIATRICS

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Humans born preterm have low nephron number and are at risk for acute kidney injury and chronic kidney disease. We plan to use a mouse model of low nephron number to study the cellular and molecular basis of kidney disease in this population. Our goal is to discover prevention and treatment strategies for acute kidney injury and the development of chronic kidney disease in humans born preterm.

PI_NAMEs: GOOD, PAMELA ISABEL (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: Acceleration;Acute;Acute Renal Failure with Renal Papillary Necrosis;Adult;Animal Model;Apoptosis;Binding;Brush Border;career;career development;CCL2 gene;Cell Death;cell injury;Cells;Cellular Metabolic Process;Cessation of life;Chronic;Chronic Kidney Failure;Clinical Research;clinical training;clinically relevant;critical period;CXCL10 gene;cytokine;Dedications;design;Development;Disease;disease phenotype;Distal;DNA;Duct (organ) structure;Endocytosis;Endowment;Environment;exposed human population;Exposure to;Fellowship;Future;Gentamicins;Gestational Age;Goals;Growth;Growth and Development function;Health;Human;human model;Impairment;improved;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Injury;Injury to Kidney;Institution;Kidney;kidney biopsy;Kidney Diseases;knowledge base;Link;LoxP-flanked allele;Lysosomes;Measures;Mentors;Metanephric Diverticulum;Mitochondria;Modeling;Molecular;Molecular Target;Morphology;mouse model;Mus;Names;Necrosis;Neonatal;neonatal human;nephrogenesis;Nephrons;nephrotoxicity;novel;Pathogenesis;Pathogenicity;Pathway Analysis;Pathway interactions;Pediatrics;Pharmaceutical Preparations;Physicians;Play;Population;Positioning Attribute;postnatal;postnatal period;Pregnancy;premature;Premature Infant;prevent;Prevention strategy;Process;Production;professor;programs;pup;Research;response;RIPK3 gene;Risk;Role;Rupture;Scientist;Signal Transduction;single-cell RNA sequencing;skills;System;targeted treatment;Testing;Tetanus Helper Peptide;Toxic effect;Training;treatment strategy;Tubular formation;Universities;uptake

PROJECT_TITLE: Cellular and Molecular Response to Gentamicin-Induced Injury in Underdeveloped Kidneys

STUDY_SECTION: DDK

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


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Childhood Injury;Clinical Research;Comparative Effectiveness Research;Emergency Care;Health Services;Neurosciences;Pediatric;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Unintentional Childhood Injury

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: PROJECT NARRATIVE This research is relevant to public health because traumatic brain injury is the leading cause of morbidity and mortality in children and adolescents. The proposed study will develop an innovative poly-matching design (PMD) for comparative clinical effectiveness research (CER) and apply causal inference strategies to assess four acute medical management/therapies for pediatric traumatic brain injuries (TBI). The ultimate goal is to provide inno- vative methods for research related to emergency medical services for children (EMSC) and build the evidence base for clinical practice.

PI_NAMEs: GRONER, JONATHAN ;LU, BO ;XIANG, HENRY  (contact)

PROGRAM_OFFICER_NAME: DIXON, CINNAMON ANNE

PROJECT_TERMS: Acute;Adolescent;Adult;Algorithms;arm;Caring;Centers for Disease Control and Prevention (U.S.);Cerebrospinal Fluid;Characteristics;Child;child services;Childhood;Clinical;clinical care;Clinical effectiveness;clinical practice;Clinical Research;Clinical Services;Clinical Trials;comparative;Complex;Data;data registry;Databases;Dependence;design;Development;Diagnostic Services;Drainage procedure;effectiveness evaluation;effectiveness research;Emergency medical service;Ensure;Equilibrium;Ethics;European;Evaluation;evidence base;Face;Foundations;Future;Goals;Government Agencies;Guidelines;Head;Health Benefit;health care quality;Health Care Research;Health Policy;Health Sciences;Healthcare;Healthcare Systems;Hospitals;improved;individual patient;innovation;interest;International;Intervention;Intracranial Pressure;Medical;Medical Records;Meta-Analysis;Methodology;Methods;mild traumatic brain injury;Modeling;Monitor;Morbidity - disease rate;mortality;Observational Study;Outcome;Outcomes Research;Patient Care;Patient-Focused Outcomes;Patients;Pattern;pediatric traumatic brain injury;Play;Policies;Policy Analysis;Policy Maker;Population Heterogeneity;Procedures;programs;Public Health;Randomized;Randomized, Controlled Trials;Research;Research Methodology;Research Personnel;response;Role;Scanning;Shapes;Social Sciences;Source;Statistical Data Interpretation;Statistical Methods;Stratification;Structure;TBI Patients;Time;Trauma;trauma care;trauma centers;Traumatic Brain Injury;treatment arm;treatment group;United States National Institutes of Health;working group;X-Ray Computed Tomography

PROJECT_TITLE: Poly-Matching Causal Inference for Assessing Multiple Acute Medical Managements of Pediatric Traumatic Brain Injuries

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Cancer;Genetics;Hematology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative  Clonal hematopoiesis of indeterminant potential (CHIP) is a common age-related conditions affecting over 50% of elderly individuals over 85 years of age that has been associated with inferior outcome in general population and solid tumor patients, higher incidence of cardiovascular disease and occasional progression to myelodysplastic syndromes and leukemia. The focus of this project is to identify the population at risk for transformation and non-malignant sequalae of CHIP, determine the impact of CHIP in bone marrow transplant donors on post-transplant outcome and define the role of CHIP in development and progression of non- hematologic cancers. If successful, our study will result in clinically relevant risk stratification leading to reduction of CHIP-related consequences and application of personalized therapeutic approaches, improved bone marrow donor selection process and implementation of preventative strategies in the future.

PI_NAMEs: GONDEK, LUKASZ PAWEL (contact)

PROGRAM_OFFICER_NAME: DI FRONZO, NANCY L

PROJECT_TERMS: Acceleration;Acute Myelocytic Leukemia;Address;Adverse event;adverse outcome;Affect;Age;age group;age related;Age Years;Aged, 80 and over;Aging;Allogenic;Biological;Biology;Blood;Blood Cells;Bone Marrow;Bone Marrow Transplantation;Cardiovascular Diseases;Cardiovascular system;Cells;Chronic;Clinical;Clinical Data;clinically relevant;Clonal Evolution;Clonal Expansion;cohort;Cohort Studies;Complication;Data;Development;Disease;DNMT3a;Donor person;Donor Selection;Dysmyelopoietic Syndromes;Elderly;Enrollment;Epigenetic Process;Event;Female;follow-up;Frequencies;Future;General Population;Genes;Genetic;genetic evolution;graft vs host disease;Growth;Hematology;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Human;human model;human very old age (85+);improved;in vivo;Incidence;Individual;Inferior;Inflammation;Inflammatory;insight;Length;leukemia;Leukemic Cell;leukemogenesis;longitudinal, prospective study;Malignant - descriptor;Malignant Neoplasms;Mutation;Natural History;Nature;Non-Hematologic Malignancy;Non-Malignant;Older Population;Oncogenic;Outcome;Pathway interactions;patient stratification;Patients;personalized therapeutic;Persons;Phenotype;Populations at Risk;post-transplant;pre-clinical;premalignant;Prevalence;Prevention strategy;Process;prognostic;progression risk;Proliferating;prospective;Prospective Studies;Publishing;Risk Factors;risk stratification;Role;Sampling;screening;self-renewal;Solid Neoplasm;Somatic Mutation;Study models;Testing;Time;Tissues;Toxic effect;Transplant Recipients;tumor

PROJECT_TITLE: The Biological Consequences of Age-related Clonal Hematopoiesis

STUDY_SECTION: MCH

STUDY_SECTION_NAME: Molecular and Cellular Hematology Study Section[MCH]


ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

ORG_STATE: CA

PHR: The increased expression of angiotensin converting enzyme (ACE) enhances the immune function of macrophages and neutrophils by altering their metabolism and increasing cell production of ATP. This proposal is to investigate exactly how ACE modifies myeloid cell metabolism to learn how to increase myeloid cell function in treating human infection, malignancy and other diseases.

PI_NAMEs: BERNSTEIN, KENNETH E (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: ACE2;Acute;adaptive immune response;Address;Affect;Angiotensin II;Angiotensin-Converting Enzyme Inhibitors;Angiotensins;Antibacterial Response;autocrine;Biochemical;Blood Pressure;Cardiovascular system;Cell Physiology;Cell Respiration;Cells;Cellular Metabolic Process;Chemicals;Chronic;Chronic Disease;Clinical;Data;Disease;Effectiveness;enzyme activity;Enzyme Induction;enzyme mechanism;enzyme substrate;Enzymes;fighting;Genetic;Goals;Human;Immune;immune function;Immune response;Infection;Inflammatory;Innate Immune Response;Knock-out;Learning;Link;lipid metabolism;Lipids;Macrophage;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Medical Research;Metabolic;Metabolism;Mus;Myelogenous;Myeloid Cells;neutrophil;novel;overexpression;Oxidative Phosphorylation;Paper;paracrine;Peptides;Peptidyl-Dipeptidase A;Phenotype;PPAR alpha;Process;Production;Proteins;Ramipril;response;Role;Solid;Superoxides;transcription factor;tumor;volunteer

PROJECT_TITLE: ACE and myeloid cell metabolism

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-D(90)]


NIH_SPENDING_CATS: Aging;Clinical Research;Digestive Diseases;Genetics;Liver Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: STANFORD

ORG_DEPT: SURGERY

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative: Cell therapy using human hepatocyte-like cells (h-iHLCs) has the potential to address the unmet need for high quality and less invasive therapies to treat liver disease. We aim to identify and modulate age-related mechanisms that affect the quality of h-iHLCs with the ultimate goal of making h-iHLCs a safe and practical technology for clinical applications in regenerative medicine, as well as in disease modeling and pharmaceutics.

PI_NAMEs: KIRCHNER, VARVARA A (contact)

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: Acute Liver Failure;Address;Adult;Affect;Age;age effect;age group;age related;age related changes;Age Years;age-related disease;aged;Allogenic;alternative treatment;Animals;Architecture;Attention;Autologous;Bilirubin;Biological Assay;Biology of Aging;Bypass;career;career development;cell age;Cell Differentiation process;Cell Maturation;Cell Physiology;Cell Reprogramming;Cell Therapy;Cell Transplantation;Cells;Cessation of life;Clinical;clinical application;Cytochrome P450;Data;Data Correlations;Development Plans;Diabetes Mellitus;Diagnosis;disease model;DNA Methylation;DNA Methyltransferase Inhibitor;Education;Elderly;embryonic stem cell;Engraftment;Epigenetic Process;epigenetic regulation;epigenome;Ethics;Exhibits;experience;Future;Gene Expression;Genes;Genetic;Genus Hippocampus;Goals;Hepatic;Hepatocyte;hepatocyte engraftment;Hepatocyte transplantation;Human;human induced pluripotent stem cells;Immune response;In Vitro;in vivo;induced pluripotent stem cell;Liver;Liver diseases;Liver Failure;liver transplantation;Macular degeneration;Mass Spectrum Analysis;Measures;Mentors;Metabolic;metabolic profile;Metabolism;minimally invasive;Monitor;Morbidity - disease rate;mortality;mouse model;multiple omics;Mus;novel;operation;Operative Surgical Procedures;Organ;Organ Transplantation;Oxygen Consumption;Pathology;Patients;Persons;Pharmacy (field);Play;Positioning Attribute;preservation;prevent;Proteins;Proteome;Protocols documentation;Publishing;Regenerative Medicine;Regulation;Rejuvenation;Research Personnel;Risk Factors;Role;Serum Albumin;Solid;Source;stem cell biology;stem cells;success;Technology;Testing;therapeutic evaluation;Training;Transaminases;Transcript;transcriptome;transcriptome sequencing;Transplant Surgeon;Transplantation;Treatment Efficacy;Tyrosinemias

PROJECT_TITLE: The effect of donor age on the function and therapeutic efficacy of human hepatocyte-like cells

STUDY_SECTION_NAME: Biological Aging Study Section[NIA-B]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Clinical Research;Genetics;Human Genome

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

ORG_STATE: MA

PHR: This project will increase the diversity of our nation’s research scientists. We will train members of underrepresented groups to seek graduate studies and succeed in research careers. We will create an annual workshop in Atlanta to facilitate genomic research and teaching within the Atlanta University Center consortium.

PI_NAMEs: BIRREN, BRUCE W. (contact)

PROGRAM_OFFICER_NAME: COLLEY, HEATHER

PROJECT_TERMS: Academic advising;Academy;Address;Admission activity;aspirate;Biomedical Research;career;career development;Career Mobility;career preparation;Collaborations;collaborative environment;college;Communication;Communities;Critical Thinking;Data Set;Development;Disparity;Education and Outreach;Educational Curriculum;Educational process of instructing;Educational workshop;Ensure;Environment;equity, diversity, and inclusion;Ethnic Population;Evaluation;evidence base;expectation;experience;Faculty;genome resource;genome sciences;Genomics;graduate school;Historically Black Colleges and Universities;human disease;improved;Incubators;Individual;Institution;Intervention;Lead;Leadership;leadership development;marginalized community;marginalized population;member;Mentors;Mentorship;Minority Groups;Morehouse School of Medicine;multidisciplinary;next generation;novel strategies;Outcome;Participant;peer;Postbaccalaureate;programs;racial population;Research;Research Personnel;Resources;Rest;Role;Scholars Program;Science;Scientist;Self Efficacy;skills;social;Social Identification;Socialization;STEM career;Structure;Students;success;successful intervention;summer institute;summer research;support network;Time;tool;Training;undergraduate student;Underrepresented Populations;Underrepresented Students;Universities;Vocational Guidance;Work

PROJECT_TITLE: Promoting Diversity, Equity, Inclusion, and Belonging in Genomic Research.

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM(O1)-G]


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research;Health Services;Machine Learning and Artificial Intelligence;Mental Health;Patient Safety

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PUBLIC HEALTH RELEVANCE:  Managing predicted burnout in RNs is important because, despite RNs comprising half of the global health workforce, there is still a critical shortage of hospital-based RNs in the U.S. While the proposed project focuses on predicting burnout in RNs, the insights derived in this work could be potentially applied to other healthcare workers (e.g., clinicians, clinical support staff) and may translate to non-healthcare workforces.

PI_NAMEs: ATHREYA, ARJUN PRASANNA (contact);BOBO, WILLIAM V

PROGRAM_OFFICER_NAME: MCNAMARA, KAREN MARIE

PROJECT_TERMS: Absenteeism;Address;administrative database;Adopted;Adoption;Adverse effects;Affect;Bioethics;burnout;care delivery;Case Study;Client satisfaction;Clinic;Clinical;cohort;coping;Data;data de-identification;Data Set;Deterioration;Discipline of Nursing;Distress;Electronic Health Record;Employee;Engineering;Ethics;experience;Florida;global health;Goals;Health;Health Personnel;Healthcare Systems;High Prevalence;Hospital Administrators;Hospitals;Individual;insight;International;interpersonal conflict;Measures;Medical Errors;Modeling;Morals;multi-task learning;Nosocomial Infections;Nurses;Occupational;Occupations;patient safety;Patient-Focused Outcomes;Patients;Performance;Performance at work;Physiological;Predictive Factor;Productivity;psychologic;public health relevance;Quality of Care;Registered nurse;Reporting;Resources;Rest;Risk;Risk Reduction;Science;Site;smart watch;Stress;synergism;Technology;Technology Assessment;Translating;Vision;wearable device;Work;Workplace;World Health Organization

PROJECT_TITLE: SCH: Wearable Augmented Prediction of Burnout in Nurses: A Synergy of Engineering, Bioethics, Nursing

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-VH-N(50)R]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases;Orphan Drug;Precision Medicine;Rare Diseases;Tuberculosis

ORG_CITY: SEATTLE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE We recently discovered that small differences in bacterial susceptibility to TB drugs are important predictors of treatment outcome, but what drives those differences is not known. This project unites three labs with highly complementary expertise to interrogate how M. tuberculosis clinical strains respond to treatment. We will apply with leading edge approaches in genetics, metabolism, gene regulation and network-based modeling to reveal fundamental new knowledge about TB that could lead directly to shorter treatment times and better treatment outcomes.

PI_NAMEs: ALLAND, DAVID ;SHERMAN, DAVID R (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, KAREN A

PROJECT_TERMS: Affect;Antitubercular Agents;Bacillus;Bacteria;Bacterial Physiology;Biological;biomarker development;candidate marker;causal variant;Cell Death;Cells;Characteristics;Chemicals;Clinical;Computer Models;Data;DNA Sequence Alteration;driving force;drug metabolism;drug relapse;Drug resistance;drug sensitivity;Drug Tolerance;Ethambutol;Event;Evolution;fitness;functional genomics;Future;Gene Expression Profile;Gene Expression Regulation;gene network;gene regulatory network;Genes;Genetic;Genetic Transcription;genetic variant;genome-wide;Genomics;global health;Health system;improved;improved outcome;in vivo;insight;Intervention;isoniazid;knock-down;Knowledge;Lead;Length;Measures;Metabolic;Metabolic Pathway;Metabolism;Methods;minimal inhibitory concentration;Modeling;Mutation;Mycobacterium tuberculosis;Network-based;new therapeutic target;novel;Patient Noncompliance;Patients;Permeability;personalized medicine;Pharmaceutical Preparations;Phenotype;Prediction of Response to Therapy;Predisposition;pressure;programs;Public Health;Radiology Specialty;rate of change;Regimen;Regulatory Pathway;Relapse;relapse patients;relapse risk;Research;resistance gene;resistance mutation;response;Rifampin;success;Surveys;System;Testing;tool;Toxic effect;treatment duration;Treatment Failure;Treatment outcome;Tuberculosis;tuberculosis chemotherapy;tuberculosis drugs;tuberculosis treatment;Variant;Work

PROJECT_TITLE: Genetic, Metabolic and Regulatory Control of MIC and Relapse in M. tuberculosis

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: Los Angeles

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative Inter-tissue communication is essential for organismal homeostasis. Our research is focused on the fundamental mechanisms by which bidirectional communication between the nervous system and the intestine regulates antioxidant activity through neuropeptide signaling. Our research will uncover new mechanisms by which reactive oxygen species regulate neuropeptide secretion, which may lead to the development of new therapies for neurodegenerative diseases linked to defective antioxidant homeostasis.

PI_NAMEs: SIEBURTH, DEREK  (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Antioxidants;Axon;Behavioral;Brain;Butyrates;Caenorhabditis elegans;Communication;Cysteine;Dense Core Vesicle;Development;Diet;Distal;Endocrine;Experimental Designs;experimental study;Genetic;Goals;gut-brain axis;Homeostasis;Hydrogen Peroxide;hypocretin;Impaired cognition;in vivo;insight;Intestinal Secretions;Intestines;Laboratories;Link;Mediating;Mitochondria;Modeling;Modification;Molecular;Nervous System;Neurodegenerative Disorders;neuron loss;Neurons;Neuropeptides;Neurosecretion;neurotransmission;neurotransmitter release;novel;novel therapeutics;Nutrient;Organism;Oxidation-Reduction;Oxidative Stress;Physiological;Play;Protein Kinase C;Proteins;Reactive Oxygen Species;receptor;Regulation;release factor;Research;response;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Site;Source;Stress;Tissues;transcription factor;vesicular release;Vitamins;Volatile Fatty Acids;water channel

PROJECT_TITLE: Stress regulation of neurotransmission

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: RICHMOND

ORG_DEPT: PHARMACOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Relevance Opioid use disorder has become a real threat to our society. This proposal will focus on the development of highly selective mu opioid receptor modulators as novel opioid use disorder treatment by applying multidisciplinary tools, including drug discovery and development, medicinal chemistry, neuropharmacology, and behavioral pharmacology. The goal of this project is to identify clinical candidates as suitable treatments for opioid use disorder.

PI_NAMEs: ZHANG, YAN  (contact)

PROGRAM_OFFICER_NAME: SOUSA, JASON CARLOS

PROJECT_TERMS: abuse liability;Acute;Affinity;Agonist;American;antagonist;Attenuated;attenuation;behavioral pharmacology;Binding;Binding Proteins;Biologic Characteristic;Biological Assay;Biological Availability;Biological Products;Buprenorphine;Categories;Cell Line;Chemicals;Chronic;Clinical;clinical candidate;compound 30;Cyclic GMP;Dependence;design;Development;Dose;drug candidate;drug development;drug discovery;Drug Kinetics;drug metabolism;effective therapy;FDA approved;Fentanyl;Food;Formulation;G-Protein-Coupled Receptors;Goals;Heroin;in silico;In Vitro;in vivo;Laboratory Research;Lead;Libraries;Ligands;Macaca mulatta;manufacture;manufacturing scale-up;Metabolic;Methadone;Modeling;molecular modeling;mu opioid receptors;multidisciplinary;Mus;Naltrexone;National Institute of Drug Abuse;Neuropharmacology;next generation;novel;Opioid;Opioid agonist;Opioid Antagonist;opioid epidemic;opioid overdose;Opioid Receptor;opioid use disorder;opioid withdrawal;Oral;Penetration;Permeability;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacotherapy;Phase;Plasma Proteins;pre-clinical;Procedures;Property;Rattus;Research;Self Administration;small molecule libraries;Societies;Stimulus;Study models;Tail;Testing;Therapeutic;Therapeutic Effect;Time;tool;Toxic effect;United States;United States Food and Drug Administration;Universities;Virginia;Water;Withdrawal;Withdrawal Symptom

PROJECT_TITLE: Mu Opioid Receptor Modulator Development to Treat Opioid Use Disorder


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: Aurora

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative: Understanding protein folding mechanisms is important for human health. This proposal investigates how a protein cotranslationally folds by developing and applying technology to image in real-time folding dynamics at the single mRNA level in living cells. Using a combination of advanced single-molecule fluorescence microscopy and novel intrabodies to distinguish unfolded and folded forms of proteins, I will study the cystic fibrosis transmembrane conductance regulator (CFTR) to address the basic questions of when, where, and how CFTR folds in living cells.

PI_NAMEs: ZHAO, NING  (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Address;Alzheimer's Disease;Bacteriophage M13;Binding;Biological Assay;cell fixing;Cell Line;Cells;Color;combat;Communities;Coupled;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;Delta F508 mutation;density;Development;Diagnostic;Disease;Engineering;experience;Fab Immunoglobulins;Fluorescence Microscopy;graduate student;Hand;Health;Heterogeneity;Human;Huntington Disease;Image;imaging modality;imaging platform;In Vitro;in vivo;Intrabody;Kinetics;Label;Left;Length;Light;Location;Measures;Messenger RNA;method development;Methods;Modeling;mRNA Translation;mutant;nanobodies;new therapeutic target;novel;Nucleotides;Parkinson Disease;Persons;Phage Display;Phase;Positioning Attribute;Postdoctoral Fellow;protein folding;protein misfolding;Proteins;Reagent;real-time images;Reporter;Research;Research Personnel;Resolution;Ribosomes;Signal Transduction;single molecule;Site;spatiotemporal;Spottings;System;Technology;Testing;thermostability;Time;Translations;Tube;Visualization;Work

PROJECT_TITLE: Imaging cotranslational protein folding with high spatiotemporal resolution in living cells

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Genetics;Infectious Diseases;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_CITY: DURHAM

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: The emergence of new malaria parasites from primate reservoirs into human populations is an increasing threat to human health, particularly in Asia and South America, and a major barrier to malaria elimination. This proposal will inform the host and parasite genetic basis of malaria’s ability to shift hosts, leading to downstream drug targets and prediction of emerging parasites.

PI_NAMEs: GOLDBERG, AMY  (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Alouatta;Americas;Asia;Back;Binding Proteins;Blood Cells;Brazil;burden of illness;Case Study;Cell Surface Proteins;Cells;Clinical;Complex;Computer Models;Computing Methodologies;cross-species transmission;Demography;Development;Drug Targeting;Environment;Erythrocytes;European;Evolution;experimental study;Face;Future;Gene Expression;Gene Family;Genes;Genetic;genetic evolution;genetic signature;Genetic Variation;Genome;genome resource;Genome Scan;genome sequencing;genome-wide;genomic data;Genomics;Goals;Health;Human;Human Genome;improved;Infection;insight;Intervention;Invaded;Life Cycle Stages;Location;Malaria;method development;Methods;Modeling;Monkeys;nonhuman primate;novel;offspring;Parasites;Pattern;Phylogenetic Analysis;Phylogeny;Plasmodium;Plasmodium falciparum;Plasmodium vivax;Population;Population Genetics;Predisposition;preference;pressure;Primates;protein structure;Proteins;Publishing;Recording of previous events;Reporting;Reticulocytes;Risk;Role;Route;Sampling;Sexual Reproduction;simulation;South America;South American;Southeastern Asia;Specificity;System;Techniques;Testing;timeline;tool;Transgenic Organisms;transmission process;Variant;whole genome;Work;Zoonoses

PROJECT_TITLE: Evolutionary dynamics of zoonotic malaria

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE. Latinx are at increased risk for Alzheimer's disease and related dementias (ADRD) compared with non- Hispanic whites. Bilingualism may reduce ADRD risk but prior studies lack detailed characterization of within- group differences among bilinguals such as age of second language (L2) acquisition, L2 proficiency, and frequency of dual language use and its relationship to cognition in the presence of neuropathology. The current study will elucidate mechanisms underlying the relationship among bilingualism, neuroimaging markers of pathology, and cognitive function, which has the potential to inform novel interventions to preserve cognitive function and reduce ADRD disparities.

PI_NAMEs: ARCE, MIGUEL  (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Adult;Age;Aging;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid;Attention;bilingualism;Biological Markers;Brain;Buffers;California;career;cerebral atrophy;Cerebrovascular Disorders;Clinical;Cognition;Cognitive;Cognitive aging;cognitive change;cognitive function;cognitive neuroscience;cognitive reserve;cognitive testing;cohort;Communities;comparison control;Cross-Sectional Studies;Data;Data Analyses;data harmonization;dementia risk;Disparity;disparity reduction;Education;Enrollment;Environmental Risk Factor;Exclusion;executive function;experience;Family;Foundations;Frequencies;Goals;health disparity;Healthcare Systems;Height;Hispanic Populations;Home;human old age (65+);imaging biomarker;Immigrant;Immigration;Impaired cognition;Intervention;Knowledge;Language;Latinx;Latinx population;Longitudinal cohort;Magnetic Resonance Imaging;Measurement;Methodology;Methods;middle age;Modeling;Nerve Degeneration;neuroimaging;neuroimaging marker;neuropathology;Neuropsychology;Not Hispanic or Latino;novel;offspring;Outcome;Pathology;Phase;Population;Population Heterogeneity;Populations at Risk;Positron-Emission Tomography;preservation;protective effect;protective factors;Proxy;Psycholinguistics;recruit;Reporting;Research;Research Personnel;resilience;resilience factor;Risk;Role;sex;Sex Differences;social culture;sociocultural determinant;Socioeconomic Status;Statistical Methods;Symptoms;tau Proteins;Training;Universities;Washington

PROJECT_TITLE: Factors of Resilience to Alzheimers Disease and Related Dementias among Latinx: The Role of Bilingualism


NIH_SPENDING_CATS: Bioengineering;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: MINNEAPOLIS

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: Project Narrative Despite the success of genome-wide association studies (GWAS), our ability to predict genetic risk remains limited, especially for people of non-European ancestry. This research proposes to uncover, and correct, statistical biases in our inference of the genetic architecture of disease risk and study genetic risk factors in underrepresented non-European populations. The findings of this research will improve the applicability of clinical genetic research to a more diverse set of people and lead to an improved understanding of the fundamental architecture of disease risk in humans.

PI_NAMEs: ZAIDI, SYED ARSLAN ABBAS (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Address;Admixture;Advisory Committees;African American population;Aging;Apoptosis;Architecture;Asian population;Award;biobank;causal variant;Cell Respiration;clinical application;Communities;Complex;Computer Simulation;computerized tools;Consanguinity;Data;Demographic Impact;Demography;Developing Countries;Diagnosis;Disease;disorder risk;DNA;Electronic Health Record;ethnic diversity;Ethnic Population;Ethnography;Genes;Genetic;genetic architecture;Genetic Epistasis;genetic predictors;Genetic Research;Genetic Risk;genetic risk factor;Genetic Structures;Genetic study;Genome;genome wide association study;Goals;Haplogroup;Heart Diseases;Human;human disease;improved;Individual;Learning Skill;Medicine;Metabolism;Methods;Mission;Mitochondria;Mitochondrial DNA;Modeling;mortality;National Institute of General Medical Sciences;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Nuclear;Pakistan;Pattern;Pennsylvania;Performance;Persons;phenome;Phenotype;Play;polygenic risk score;Population;Population Heterogeneity;precision medicine;Premature Birth;Prevention;programs;rare variant;Recording of previous events;Research;Residual state;Resources;Risk;risk prediction;Role;Scientist;Shapes;simulation;South Asian;Statistical Bias;Statistical Methods;Structure;success;Testing;Training;trait;Uncertainty;United States National Institutes of Health;Universities;Variant;Veterans

PROJECT_TITLE: Leveraging human evolutionary history to improve our understanding of complex disease architecture


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: NARRATIVE The fields of neurology and neurosurgery are poised to make rapid advances in the treatment of neurological disorders, but the success of this endeavor depends on the availability of a cadre of academically based clinician scientists who are engaged in translational research, and who will catalyze the translation of advances between the laboratory and the bedside. The proposed program has been refined over three project periods and provides a facilitated and intensively mentored pathway to a research career as a physician-scientist in the clinical neurosciences.

PI_NAMEs: AGUIRRE, GEOFFREY KARL (contact);CHEN, HAN-CHIAO ISAAC;DETRE, JOHN A

PROGRAM_OFFICER_NAME: WEIGAND, LETITIA ALEXIS

PROJECT_TERMS: Adult;career;career development;Clinical;Clinical Investigator;Communities;Country;design;Development;Disease;Education;Education Projects;experience;Faculty;Fellowship;Fostering;Home;Institution;Interdisciplinary Study;Interview;K-Series Research Career Programs;Laboratories;Laboratory Research;matriculation;medical schools;Medicine;member;Mentors;Mentorship;Mission;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;Neurology;Neurosciences;Neurosciences Research;neurosurgery;Pathway interactions;Pediatric Hospitals;Pediatric Neurology;Pennsylvania;Phase;Philadelphia;Physicians;Procedures;programs;Radial;Research;research faculty;Research Methodology;Research Personnel;Research Training;Residencies;responsible research conduct;Schools;Scientist;success;Training;Training Programs;Translational Research;Translations;Universities;University Hospitals;Visit

PROJECT_TITLE: Research Training Program in Disease-Oriented Neuroscience (R25)

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-B (03)]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Cardiovascular

PHR: PROJECT NARRATIVE This past decade has been marked by a cessation in the previous steady decline of cardiovascular deaths, and potentially even a slight uptick, creating a public health imperative to better understand the causes and treatments for cardiovascular disease. Building on an exceptionally strong prior track record of academic training, this proposal seeks to train the next generation of investigators with modern techniques for cardiovascular research, including in new areas particularly relevant to the aging demographics of the American population, leveraging new insights into mechanisms of cardiovascular disease for all and especially for women, and the digital health revolution. Working with a diverse and experienced cohort of faculty preceptors, trainees will immerse themselves in both experiential/project-based learning as well as didactic training in critical elements of cardiovascular science, to emerge as future thought leaders to better understand, diagnose, and treat a broad spectrum of cardiovascular diseases.

PI_NAMEs: PINSKY, DAVID J. (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TITLE: Multidisciplinary Cardiovascular Research Training

STUDY_SECTION: NITM

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


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

PHR: Project Narrative  An in-depth Genomic Medicine education, as provided by a master’s degree, is needed to prepare the medical students for careers analyzing the human genome in academic research centers, government, and industry, including biotechnology firms, pharmaceutical companies, and clinical laboratories. Thus, there is a great need for master’s education programs that provide health professional and related trainees with the knowledge and skills required to manipulate, annotate, and interpret human genome data, and a foundation for pursuing genomics research. To address this need, we will leverage our evolving expertise in analysis of genomic data and education (Nara Sobreira, Joann Bodurtha, David Valle, Weiyi Mu, Nancy Hueppchen, Kim Doheny, Winston Timp, Xiao Peng, Jim Stevenson, Dane Witmer, Carolyn Applegate) and the unique tools and resources available at JHUSOM such as the ones offered by the Office of Online Education (Robert Kearns), by the Johns Hopkins Advanced Academic Programs (Robert Lessick), and PhenoDB Teaching Tool to develop a Genomic Medicine Master’s program that will address the expanding need for genomic literacy and create opportunities for these individuals to train others.

PI_NAMEs: SOBREIRA, NARA  (contact)

PROJECT_TERMS: 3-Dimensional;academic program;Active Learning;Address;Ambulatory Care Facilities;Assessment tool;Bioinformatics;bioinformatics resource;Biotechnology;career;Classification;Clinic;Clinical;Clinical Medicine;cohort;Communication;Competence;Copyright;Course Content;curriculum development;Data;Data Analyses;Decision Making;Degree program;Development;Diagnosis;diagnostic tool;Disease;DNA sequencing;E-learning;Education;Educational Curriculum;Educational process of instructing;Educational workshop;ethical, legal, and social implication;Europe;evidence base;exome sequencing;Exposure to;Faculty;Family;Foundations;Free Will;Genetic;Genetic Processes;genetic testing;Genetic Variation;Genome;genome sequencing;genomic data;Genomic medicine;Genomics;Government;graduate student;Guidelines;Health Professional;Healthcare;high throughput analysis;Hour;Human Genome;Hybrids;improved;Individual;Industry;Informatics;Institution;International;Knowledge;Laboratories;Learning;learning materials;lectures;Libraries;Licensing;Life;literacy;Malignant Neoplasms;Master of Science;Medical Genetics;Medical Informatics;medical schools;Medical Societies;Medical Students;meetings;Methods;Mutation;Paper;Participant;patient health information;Patients;Persons;Pharmacologic Substance;Phenotype;Physicians;Portuguese;Postdoctoral Fellow;proband;Process;Professional counselor;programs;Publications;Reading;Recording of previous events;Research;Resources;Rotation;skills;Slide;South America;Spanish;Structure;Students;Surveys;Test Result;Testing;The Jackson Laboratory;tool;tool development;Training;Translating;Translational Research;Universities;variant of unknown significance;virtual;whole genome;Work

PROJECT_TITLE: Genomic Medicine Master of Science (M.S.) Degree Program

STUDY_SECTION_NAME: Special Emphasis Panel[ZHG1 HGR-W (O1)]


ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Overall Program Narrative Dysregulated blood clotting is a major cause of heart attacks and strokes and underlies bleeding diseases. This program uses a multi-disciplinary approach to understand basic molecular mechanisms of the blood clotting reactions to reveal new approaches for the treatment of human diseases.

PI_NAMEs: KRISHNASWAMY, SRIRAM  (contact)

PROGRAM_OFFICER_NAME: WARREN, RONALD Q

PROJECT_TERMS: Active Sites;Address;aptamer;Area;Atomic Force Microscopy;base;Biochemical;Biochemistry;Biological;Biological Process;Biology;biophysical analysis;biophysical techniques;Blood coagulation;Blood Coagulation Disorders;Blood Vessels;Chemistry;Coagulation Process;cofactor;Complex;Deuterium;Disease;Ensure;Enzyme Precursors;enzyme substrate;Enzymes;Factor V;Factor Va;gene therapy;Goals;Hemophilia A;Hemophilia B;Hemorrhage;Hemostatic Agents;Hemostatic function;human disease;human morbidity;human mortality;Hydrogen;improved;Individual;inhibitor;insight;interdisciplinary approach;interest;Kinetics;Knowledge;Life;Ligands;Link;Membrane;membrane assembly;Membrane Proteins;Molecular;Molecular Biology;Multienzyme Complexes;Myocardial Infarction;novel;novel strategies;novel therapeutic intervention;Participant;Peptide Hydrolases;Physiology;Play;programs;protein expression;Proteins;prothrombinase complex;Reaction;Recombinants;Records;Regulation;Regulation of Proteolysis;Research;Research Personnel;response;Rest;RNA;RNA Probes;Role;Series;Serine Protease;Specificity;Stroke;structural biology;Structure;Substrate Specificity;synergism;Techniques;Testing;Therapeutic;Thrombosis;Translating;Translations;treatment strategy;Trypsin;Variant;Western World;X-Ray Crystallography

PROJECT_TITLE: Hemostasis and Thrombosis: Chemistry, Biology and Physiology

STUDY_SECTION: HLBP

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP (OA)]


NIH_SPENDING_CATS: Cardiovascular;Hematology

PHR: Core A Narrative Core A provides administrative support and scientific leadership for the program.

PROJECT_TERMS: Biochemical;Biology;Chemistry;computer program;Computer software;Data Analyses;Ensure;Evaluation;Extramural Activities;Fees;Financial Support;Funding;Goals;Graph;Hemostatic function;Individual;Institution;Leadership;Licensing;meetings;member;Occupational activity of managing finances;operation;Participant;Physiology;programs;Scientific Evaluation;Services;structural biology;Thrombosis;Visit

PROJECT_TITLE: Administrative Core


PHR: Core B Narrative Core B assists the program in molecular biology, recombinant protein expression, protein purification, x- ray crystallography, small angle x-ray scattering, Cryo-EM, hydrogen-deuterium exchange and atomic force microscopy. These services are essential to the program directed towards establishing the molecular basis for the reactions of hemostasis.

PROJECT_TERMS: Acids;Address;Affinity;analytical ultracentrifugation;Area;Atomic Force Microscopy;Awareness;beamline;Biology;Cell Line;Chemistry;Chromatography;Coagulation Process;Collection;Core Facility;Coupled;Cryoelectron Microscopy;Crystallization;Data;Data Analyses;Data Collection;data modeling;Deuterium;Development;Docking;Electron Microscopy;Ensure;Equity;experience;expression vector;Factor V;Factor VIII;Fees;Foundations;Goals;Hemostatic function;high end computer;Human Resources;Hydrogen;Image;in silico;Individual;interest;Kinetics;Laboratories;liquid chromatography mass spectrometry;Mammalian Cell;manufacturing run;Measurement;Measures;member;model building;Modeling;Molecular;Molecular Biology;Motivation;overexpression;parallel computer;particle;Pennsylvania;Physiology;Plasma Proteins;Post-Translational Protein Processing;Preparation;Production;Productivity;programs;Property;protein expression;protein purification;Proteins;Protocols documentation;Quality Control;Reaction;Reagent;Recombinant Proteins;Recombinants;reconstruction;repository;Research Personnel;Resolution;Resources;Roentgen Rays;Running;Sampling;Schedule;screening;sedimentation equilibrium;sedimentation velocity;Series;Serum;Services;skills;stable cell line;structural biology;Structure;success;Synchrotrons;Thrombosis;Time;Titan;Training;Transfection;Universities;Variant;Vitamin K;Work;X-Ray Crystallography;Yeasts

PROJECT_TITLE: Molecular Biology, Protein Expression and Structural Biology


NIH_SPENDING_CATS: Cardiovascular;Hematology;Immunization

PHR: Project 1 Narrative Excessive blood clotting is a major cause of heart attacks and strokes in the United States and also underlies ~25% of cancer-related death. Our research brings new concepts and methodologies to bear on understanding basic molecular mechanisms underlying the blood clotting reactions. Our findings will address important but unresolved aspects of function to yield novel strategies for interfering with the formation of life-threatening blood clots in human disease.

PROJECT_TERMS: Acidic Region;Active Sites;Address;Affect;Anions;antibody libraries;aptamer;Area;Bacteriophage M13;base;Behavior;Binding;Binding Sites;Biochemistry;Biology;biophysical analysis;Blood coagulation;Calorimetry;cancer procoagulant;Cessation of life;Chemistry;Coagulation Process;cofactor;Collaborations;Complex;design;Development;Disease;Distant;Enzymatic Biochemistry;Enzyme Precursors;Enzymes;Equilibrium;Excision;Face;Factor IXa;Factor V;Factor Va;Factor VIII;Factor Xa;Foundations;Goals;Hemostatic Agents;Hemostatic function;human disease;Immunization;Impairment;inhibitor;insight;Kinetics;Lead;Life;Ligand Binding;Ligands;Light;Link;Llama;Malignant Neoplasms;Measurement;Membrane;Methodology;Molecular;Molecular Conformation;Multienzyme Complexes;Myocardial Infarction;nanobodies;novel;novel strategies;Peptide Hydrolases;Peptides;Physiology;polypeptide;Positioning Attribute;prevent;Protein Family;protein function;Proteins;Proteolysis;Prothrombin;prothrombinase complex;Reaction;Research;response;RNA;Site;small molecule;Specificity;Stroke;structural biology;Structure;Testing;therapeutic target;Thermodynamics;Thrombin;Thromboplastin;Thrombosis;Titrations;United States;Variant;Vascular Diseases;Work

PROJECT_TITLE: Macromolecular Recognition in Coagulation


PHR: PROJECT 2-PROJECT NARRATIVE The formation of a blood clot following vascular injury is an essential defensive mechanism that is highly regulated. This proposal seeks to better understand how one clotting factor, factor V, is activated and participates in the regulation of blood coagulation. Mechanisms underlying these processes have relevance for better understanding and possibly treating the pathological states of bleeding and thrombosis.

PI_NAMEs: CAMIRE, RODNEY M (contact)

PROJECT_TERMS: Acceleration;Acidic Region;activated Protein C;Address;Adopted;Affect;Affinity;Antibodies;Anticoagulants;Atomic Force Microscopy;Autoantibodies;Binding;Binding Sites;Biological Assay;Biology;biophysical techniques;Blocking Antibodies;Blood coagulation;Blood Coagulation Disorders;Blood Coagulation Factor;cancer procoagulant;Chemistry;Clinical;Coagulation Process;cofactor;Data;Development;Elements;Ensure;Epitopes;Equilibrium;Excision;Factor V;Factor V Deficiency;factor V Leiden;Factor Xa;Gatekeeping;Generations;Goals;Hemorrhage;Hemorrhagic Disorders;Hemostatic Agents;Hemostatic function;improved;in vivo;Injury;insight;Knowledge;Ligands;Light;Mediating;Minor;mouse model;Mutation;novel;novel therapeutic intervention;Pathologic;Pathway interactions;Patients;Phenotype;Physiological;Physiology;Plasma;Play;Process;Property;Protein S;Proteins;Proteolysis;prothrombinase complex;Regulation;Resistance;Risk;RNA Splicing;Role;Series;Structure;System;Testing;Texas;Therapeutic;Thrombin;Thrombosis;tubulin-specific chaperone C;Variant;vascular injury;Work

PROJECT_TITLE: Structural Correlates of (Pro)Cofactor Function


PHR: Project Narrative Coagulation enzymes form macromolecular complexes to modulate important biological processes that are critical to normal health but become dysregulated in disease. One critical pathway that needs to be exquisitely controlled for human life is the coagulation system as to much blood coagulation leads to thrombosis, pathological blood clotting, and potentially death if it occurs in vital organs whereas to little coagulation can result in life threatening bleeding. In this proposal we will explore how such coagulation protein interactions tightly regulate this essential blood coagulation process using combinatorial chemistry and chemical biology approaches to generate novel probes for these processes. The results of these studies will yield a more thorough understanding of blood coagulation and potentially new therapeutic agents to limit thrombosis and bleeding in acute care settings.

PI_NAMEs: SULLENGER, BRUCE ALAN (contact)

PROJECT_TERMS: activated Protein C;Active Sites;acute care;Animal Feed;Animal Model;Anticoagulants;Antidotes;Antithrombin III;aptamer;Binding;Biological Assay;Biological Process;Biology;bivalirudin;Blood;Blood coagulation;Blood Coagulation Factor;blood coagulation process;Blood specimen;Cardiopulmonary Bypass;Cessation of life;Chemicals;Chemistry;clinical application;clinically relevant;Coagulation Process;cofactor;combinatorial chemistry;cost;Coupled;Critical Pathways;Data;design;Devices;Disease;Enzymes;Extracorporeal Membrane Oxygenation;Factor Va;Factor Xa;Factor XIa;Family suidae;Funding;Generations;Health;Hemophilia A;Hemorrhage;Hemostatic function;Hirudin;Human;In Vitro;in vivo Model;inhibitor;invention;Knowledge;Laboratories;Life;Ligands;Link;Macromolecular Complexes;Modeling;Mus;Nature;novel;novel therapeutics;Oligonucleotides;Organ;Pathologic;Patients;Peptide Hydrolases;Peptides;Physiology;Plasma;Process;Program Research Project Grants;Protease Inhibitor;protein purification;Proteins;Research;Resolution;RNA;Roentgen Rays;Series;small molecule;Specificity;Structure;System;Therapeutic Agents;Thrombin;Thromboplastin;Thrombosis;Ticks;Whole Blood

PROJECT_TITLE: RNA Aptamers as Probes and Modulators of Coagulation


PHR: PROJECT 4-PROJECT NARRATIVE The formation of a blood clot following vascular injury is an essential defensive mechanism that is highly regulated. Some people have inherited bleeding disorders because they are missing essential clotting factors such as factor VIII, IX, of X. This proposal seeks to both better understand how these clotting factors work together in the regulation of blood coagulation and to use this improved understanding to develop new and better therapies for these bleeding disorders.

PI_NAMEs: SAMELSON-JONES, BEN J (contact)

PROJECT_TERMS: Address;Adopted;Adult;Age;Amino Acid Substitution;analog;Animals;Binding;Biochemical;Biology;Bispecific Antibodies;Blood coagulation;Blood Coagulation Disorders;Blood Coagulation Factor;cancer procoagulant;Chemistry;Child;Clinical;clinically relevant;Coagulation Process;cofactor;Complex;Data;Disease;Elements;Enzyme Kinetics;experimental study;F8 gene;Factor VIII;Factor VIIIa;Fluorescence;Functional disorder;gain of function;gene therapy;Gene Transfer;Genotype;Hemophilia A;Hemophilia B;Hemostatic Agents;Hemostatic function;Human;Hyperactivity;improved;In Vitro;in vitro activity;in vivo;in vivo evaluation;Infusion procedures;Inherited;Injury;insight;Lead;Ligands;loss of function;mimetics;Modeling;Molecular;molecular assembly/self assembly;Molecular Conformation;mouse model;Multienzyme Complexes;Mus;novel;novel therapeutic intervention;novel therapeutics;Patients;Peptide Hydrolases;Persons;Pharmaceutical Preparations;Physiology;programs;Prophylactic treatment;protein purification;Proteins;Recombinant Proteins;Recombinants;Regulation;Resources;Risk;Role;Safety;Scanning Electron Microscopy;Structure;subcutaneous;synergism;System;Testing;Therapeutic;Thrombin;Thrombosis;Translating;translational potential;Variant;vascular injury;Work

PROJECT_TITLE: Translating Mechanistic Insights into Intrinsic Xase Function


NIH_SPENDING_CATS: Data Science;Neurosciences

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative The knowledge in basic neuroscience has grown exponentially over the past generation, but there is a gap in bringing those discoveries to patients with disorders of the brain, spinal cord, and peripheral nerves. The Neurology, Neurosurgery, and Neuropathology Pittsburgh Research Education Program (N3-PREP) is designed to increase the number of well-prepared physician-neuroscientists from the University of Pittsburgh who will progress to being at the forefront of research that will ultimately reduce the burden of neurologic diseases. Our goal is to train the next generation of physician-neuroscientists in basic science, translational science, data science, and clinical (patient-oriented) research through a strongly mentored approach, in an environment ripe with physical and faculty resources across the translational spectrum of neuro-focused research.

PI_NAMEs: HADJIPANAYIS, CONSTANTINOS GEORGE;KOFLER, JULIA K;PENNELL, PAGE BUCKHANNAN (contact)

PROJECT_TERMS: Address;Adult;Advisory Committees;Anatomy;Applications Grants;Basic Science;big-data science;Biomedical Research;Brain Diseases;career;career development;Caring;Clinical;Clinical Research;clinical training;clinical translation;Communication;Competence;Country;Data Science;design;Diagnostic;Education;education research;Educational Curriculum;Environment;Experimental Designs;Faculty;Fellowship;Fostering;Funding;Generations;Goals;Grant;Grant Review;Incubators;Infrastructure;innovation;Integrated Health Care Systems;interest;K-Series Research Career Programs;Knowledge;knowledge base;Laboratories;Life;matriculation;medical schools;Mentors;Methodology;Minority Groups;Nervous System Disorder;Neurobiology;Neurology;neuropathology;Neurosciences;Neurosciences Research;Neurosurgeon;neurosurgery;next generation;Participant;Pathology;Pathway interactions;patient oriented;patient oriented research;patient population;Patients;Pediatric Neurology;Peripheral Nerves;Persons;Physicians;Positioning Attribute;primary outcome;Principal Investigator;Program Development;programs;Publications;Research;research facility;research faculty;Research Personnel;Research Training;Residencies;Resources;responsible research conduct;Scientist;secondary outcome;skills;Spinal Diseases;Structure;Study Section;success;Therapeutic;Time;Training;Training and Infrastructure;Translating;translational pipeline;Translational Research;Underrepresented Minority;United States National Institutes of Health;Universities;Writing

PROJECT_TITLE: N3-PREP (Neurology, Neurosurgery, & Neuropathology Pitt Research Education Program)


NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Genetics;Human Genome;Kidney Disease;Pediatric;Polycystic Kidney Disease

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The proposed research is relevant to public health because it focuses on identifying cell-specific mitochondrial differences between and across cell types during autosomal dominant polycystic kidney disease (ADPKD) progression. We anticipate that similar to other conditions where mitochondria have central roles in disease pathogenesis, the proposed studies will identify contributions of mitochondrial dysfunction and transcriptional diversity to disease initiation and progression. These advances have the potential to transform the development of precision-targeted therapeutics and biomarkers for monitoring ADPKD, drug selection, and drug dosage; all unmet clinical ADPKD needs relevant to NIH’s mission of improving human health.

PI_NAMEs: LASSEIGNE, BRITTANY NICOLE (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: aerobic glycolysis;Alternative Splicing;Animal Model;Autosomal Dominant Polycystic Kidney;Biological Markers;Calcium;Cell Culture Techniques;cell type;Cells;Classification;Clinical;Code;Complement;Complex;Cyst;Cystic kidney;Data;Data Science;Deposition;Development;differential expression;digital object identifier;Disease;Disease Progression;DNA copy number;dosage;drug testing;Epigenetic Process;FDA approved;Functional disorder;Gene Expression;Gene Expression Profile;Genes;Genetic Transcription;Genome;genome sciences;Glycolysis;Growth;Health;Hepatotoxicity;Hereditary Disease;heteroplasmy;Human;improved;In Situ;Individual;innovation;intercellular communication;Kidney;Longevity;Magnetic Resonance Imaging;Maps;Measures;Mediating;Metabolic;Mission;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial dysfunction;mitochondrial genome;Modeling;Molecular;Molecular Profiling;Monitor;mouse model;Mus;Mutation;novel strategies;Oxidative Phosphorylation;Pathogenesis;Pathway interactions;Patients;Pattern;Pharmaceutical Preparations;Phenotype;PKD2 protein;polycystic kidney disease 1 protein;preference;Process;programs;Proprotein Convertase 1;Proprotein Convertase 2;Proteins;Public Health;recruit;Research;RNA;Role;single cell ATAC-seq;single-cell RNA sequencing;Spliced Genes;Stains;targeted biomarker;Targeted Research;targeted treatment;Testing;Therapeutic;therapeutic candidate;therapeutic target;Tissues;tolvaptan;Training;Transcript;Translations;Tubular formation;United States National Institutes of Health;uptake;urinary;Variant;Warburg Effect;web app;Wild Type Mouse

PROJECT_TITLE: Differentiating slow from rapidly progressive ADPKD by cell-specific mitochondrial and transcriptional profiles

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Project Narrative The education and training of the next generation of MD and Ph.D. researchers are essential to continued progress in lung health. This training application fills a critical need because it prepares scientists to work at the cutting edge of biomedical research in lung research. Therefore, this training program focuses on mentoring, career development, and advanced degrees in basic and translational research applied to lung diseases.

PI_NAMEs: KHERADMAND, FARRAH  (contact);ROSAS, IVAN O.

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Research Training;respiratory

PROJECT_TITLE: BCM-Respiratory Research Training


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

PHR: OVERALL NARRATIVE The proposed Program is relevant to public health because it seeks to discover fundamental principles of cancer etiology, evolution, and evasion of response to therapy, focusing on the childhood malignancy neuroblastoma. The research is highly relevant to the NIH mission and the urgent unmet need of developing rational evidence- based therapeutic strategies to reduce the health burden of cancer. This integrated multi-disciplinary Program is designed to continue to catalyze improved cure rates with decreased morbidity for patients with high-risk neuroblastoma, and many advances will be applicable to the field of cancer in general.

PI_NAMEs: MARIS, JOHN M (contact)

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Achievement;Address;Adolescent;Adult;Agreement;Automobile Driving;Basic Science;bench to bedside;Biological Markers;Cancer Burden;Cancer Etiology;cancer therapy;candidate identification;Cell model;Cells;Cessation of life;Child;Child Care;Childhood;Childhood Solid Neoplasm;clinical predictors;Clinical Research;Clinical Trials;Collection;Combined Modality Therapy;Complex;Coupled;Data;Data Set;design;Development;Disease;Ecosystem;Engineering;Epigenetic Process;epigenomics;evidence base;Evolution;experience;experimental study;Goals;Health;Heterogeneity;high risk;Human;Immunocompetent;Immunooncology;Immunotherapy;improved;improved outcome;inhibitor;innovation;insight;Institution;Intervention;Leadership;Malignant Childhood Neoplasm;Malignant Neoplasms;Mission;Modeling;Modernization;Molecular;Morbidity - disease rate;Motivation;mouse model;multidisciplinary;Multiomic Data;Mutation;neoplastic cell;Neuroblastoma;neuroblastoma cell;new therapeutic target;Newly Diagnosed;novel;novel marker;novel strategies;novel therapeutics;Oncogenic;Paper;patient derived xenograft model;patient population;Patient-Focused Outcomes;Patients;Pediatric Oncology Group;Phase;phase 3 testing;Phase I Clinical Trials;Phase II Clinical Trials;phase III trial;Physicians;Play;Population;pre-clinical;Pre-Clinical Model;preclinical trial;pressure;Probability;Productivity;programs;Public Health;Publications;Recurrent disease;Refractory;Relapse;Research;research clinical testing;Research Design;Research Personnel;Resistance;resistance mechanism;Resolution;Resources;response;Role;Sampling;small molecule therapeutics;Structure;Sympathetic Nervous System;symposium;targeted radiotherapeutic;targeted treatment;Technology;Testing;Therapeutic;therapeutic candidate;Therapeutic Intervention;Therapy Clinical Trials;therapy resistant;Time;Translating;Translational Research;Translations;Treatment Failure;treatment response;tumor;tumor microenvironment;tumorigenesis;United States National Institutes of Health;Work

PROJECT_TITLE: Discovering and Exploiting Mechanisms of Neuroblastoma Therapy Resistance

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RPRB-J (O1)]


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

PHR: NARRATIVE Project 1 is relevant to public health because it seeks to discover the fundamental reasons why cancer becomes resistant to therapy by understanding solid tumor cellular heterogeneity and adaptation to modern therapies, within a Program focused on the childhood malignancy neuroblastoma. The research is highly relevant to the NIH mission and the urgent unmet need of developing rational evidence-based therapeutic strategies to reduce the health burden of high-risk neuroblastoma, and perhaps other human cancers.

PI_NAMEs: MOSSE, YAEL P (contact)

PROJECT_TERMS: Address;ATAC-seq;ATRX gene;BCL2L1 gene;Biological Assay;Biological Markers;cancer therapy;Cell Nucleus;Cell Survival;Cell Therapy;Cells;Certification;chemoradiation;Chemoresistance;chemotherapy;childhood cancer mortality;chimeric antigen receptor;Chimeric Proteins;Clinical;Clinical Trials;Collaborations;Complex;Data;design;Detection;Diagnosis;Diagnostic;Diapause;Disease;Disease Progression;disorder risk;Epigenetic Process;epigenomics;Etiology;Europe;evidence base;Evolution;EZH2 gene;fitness;Funding;Future;gain of function mutation;Gene Frequency;gene panel;Genes;Genetic Heterogeneity;genetic variant;Genome;Genomics;Goals;Health;Heterogeneity;high risk;Human;Immunotherapeutic agent;Immunotherapy;improved;improved outcome;Indolent;industry partner;inhibitor;Knowledge;Left;Life;Major Histocompatibility Complex;Malignant - descriptor;Malignant Childhood Neoplasm;Malignant Neoplasms;MAP Kinase Gene;Mediating;Mediator;Methods;Mission;Modeling;Modernization;Molecular;Molecular Profiling;molecular targeted therapies;Monitor;multiple omics;mutant;Mutate;Mutation;Neuroblastoma;neuroblastoma cell;new therapeutic target;Newly Diagnosed;next generation sequencing;North America;Oncogenes;Oncogenic;Oncoproteins;Operative Surgical Procedures;Outcome;Pathway interactions;patient population;Patient-Focused Outcomes;Patients;Pediatric Oncology;Pediatric Oncology Group;Peptides;peripheral blood;phase 3 study;phase III trial;Phenotype;Plasma;pre-clinical;pressure;prevent;Process;programs;Proteins;Proteome;Public Health;Receptor Protein-Tyrosine Kinases;Recurrence;Relapse;Research;Research Personnel;Resistance;response;Sampling;sequencing platform;side effect;single cell technology;Single Nucleotide Polymorphism;single-cell RNA sequencing;small molecule;Solid Neoplasm;System;Technology;telomere;Testing;Therapeutic;therapeutic target;Therapeutically Targetable;therapy development;therapy resistant;Time;timeline;Tissues;transdifferentiation;Transforming Growth Factor beta;Translating;Treatment Failure;tumor;tumor DNA;tumor heterogeneity;tumorigenesis;United States National Institutes of Health;Validation;Work

PROJECT_TITLE: Targeting evolving therapy resistance


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

PHR: PROJECT 2 NARRATIVE Distinct adrenergic (ADR) and mesenchymal (MES) epigenetic states exist in NB, likely contributing to therapy resistance. We discovered that the MES state is associated with impaired responses to the immunotherapy dinutuximab, an FDA-approved antibody directed against GD2, a glycolipid on the surface of NB cells, and that the lysine methyl transferase EZH2 and the scaffolding protein MEN1 (menin) both regulate cell-surface GD2 levels in NB. Our proposal tests chromatin modifying compounds, including clinical inhibitors of EZH2 and menin, hypothesizing that these agents will transdifferentiate MES NB models into an ADR-like state, thereby increasing expression of targets critical to both small molecule inhibitors and to immunotherapies, leading to enhanced responses, meeting the NIH mission of improving patient outcomes.

PI_NAMEs: WEISS, WILLIAM A (contact)

PROJECT_TERMS: Address;Adrenergic Agents;Antibodies;ARID1A gene;ATRX gene;CAR T cell therapy;CD47 gene;Cell Line;Cell model;Cell surface;Cells;chemical genetics;Chemicals;chemotherapy;Child;Childhood Extracranial Solid Tumor;Chromatin;Clinical;Collaborations;Combined Modality Therapy;Complex;CRISPR screen;CRISPR/Cas technology;Data;Dependence;Development;Down-Regulation;Embryonal Neoplasms;Enhancers;Enzymes;Epigenetic Process;epigenetic therapy;EZH2 gene;FDA approved;GD3-synthase;Genes;Genetic;genetic approach;Genetic Transcription;Genetically Engineered Mouse;genome-wide;Germ Lines;Glycolipids;histone methyltransferase;Histone-Lysine N-Methyltransferase;Human;Immunocompetent;Immunotherapy;Impairment;improved;In Vitro;in vivo;inhibitor;inhibitor therapy;interest;Lysine;meetings;member;Menin;Mesenchymal;Mesenchymal Differentiation;Mission;MLL gene;Modeling;mouse model;Mutation;MYCN gene;NBPhox protein;Neuroblastoma;neuroblastoma cell;NOTCH3 gene;novel;Pathogenesis;Patient-Focused Outcomes;Peptides;Play;Polycomb;pre-clinical;programs;Proteins;Receptor Protein-Tyrosine Kinases;Resistance;resistance mechanism;response;Role;Scaffolding Protein;small hairpin RNA;small molecule;small molecule inhibitor;Surface;targeted treatment;Testing;Therapeutic;therapy resistant;transdifferentiation;Transferase;tumor growth;United States National Institutes of Health

PROJECT_TITLE: Targeting neuroblastoma cell state plasticity


NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Immunotherapy;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PROJECT 3 NARRATIVE Project 3 brings a unique perspective to the program project by focusing on external mechanisms (the tumor microenvironment) that – combined with intrinsic mechanisms (genetic and epigenetic alterations in tumor cells) - lead toward therapy resistance in neuroblastoma. The project has a focus on tumor-associated macrophages and cancer-associated fibroblasts that are a source of numerous inflammatory cytokines/chemokines activating TGFb-dependent and -independent pathways that promote the emergence of therapy resistant mesenchymal neuroblastoma cells. Discoveries made will lead to the preclinical testing of inhibitors of TGFb and JAK/STAT3 and to the development of TGFb resistant cellular therapies in combination with chemo-and immuno-therapy.

PI_NAMEs: ASGHARZADEH, SHAHAB  (contact)

PROJECT_TERMS: 3-Dimensional;Activated Natural Killer Cell;Adrenergic Agents;Attention;Biological Assay;CCL2 gene;CD276 gene;cell motility;Cell Therapy;Cells;chemokine;chemotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;clinical application;clinically relevant;combinatorial;Complex;cytokine;Cytometry;cytotoxic;Cytotoxic Chemotherapy;cytotoxicity;Data;Deposition;Development;Dominant Negative Receptor;Drug resistance;early phase clinical trial;efficacy evaluation;engineered T cells;Engineering;Environment;Epigenetic Process;Extracellular Matrix;Fibroblasts;Funding;Genetic;Growth;Heterogeneity;high risk;Human;Image;Immune;immune cell infiltrate;immune checkpoint;Immuno-Chemotherapy;Immunodeficient Mouse;Immunofluorescence Immunologic;Immunotherapy;In Vitro;in vivo;in vivo Model;Individual;Infiltration;Inflammatory;inflammatory milieu;inhibitor;Interleukin-6;Invaded;JAK2 gene;Knowledge;Lead;MADH2 gene;Malignant Neoplasms;Mediating;Mesenchymal;mesenchymal stromal cell;metabolic fitness;Modeling;Natural Killer Cells;Neoplasm Metastasis;neoplastic cell;Neuroblastoma;neuroblastoma cell;NF-kappa B;novel;novel marker;novel therapeutics;Outcome;Pathway interactions;Patients;Phenotype;Play;Population;Population Heterogeneity;pre-clinical;Preclinical Testing;Predisposition;Production;programs;Proteins;Protocols documentation;Publishing;Refractory;Relapse;Resistance;Rho-associated kinase;Role;Signal Pathway;Source;Specificity;STAT3 gene;Subgroup;synergism;T-Lymphocyte;targeted treatment;Testing;Therapeutic;therapeutic evaluation;Therapy Evaluation;therapy resistant;Transforming Growth Factor beta;Transforming Growth Factors;Translating;Treatment Efficacy;treatment response;tumor;Tumor Markers;tumor microenvironment;tumor progression;Tumor-associated macrophages;tumor-immune system interactions;tumorigenic;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Tumor microenvironment-dependent therapy resistance


PHR: PROJECT NARRATIVE Project 4 is relevant to public health because it seeks to discover the fundamental reasons why cancer becomes resistant to immunotherapies such as antibodies and chimeric antigen receptor (CAR) T cells within a Program focused on the childhood malignancy neuroblastoma. The research is highly relevant to the NIH mission and the urgent unmet need of developing rational, evidence-based effective therapeutic strategies to reduce the health burden of high-risk neuroblastoma and other human cancers.

PI_NAMEs: MAJZNER, ROBBIE G. (contact)

PROJECT_TERMS: Adrenergic Agents;Antibodies;Antigen Targeting;Antigens;Automobile Driving;Biological;Biology;cancer type;CD276 gene;Cell Density;cell killing;Cell Physiology;Cell surface;Cells;chemotherapy;Child;Childhood Solid Neoplasm;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;clinically relevant;Credentialing;Data;density;design;Disease;Dose;Down-Regulation;effective therapy;Effectiveness;Elements;Engineering;Epigenetic Process;evidence base;exhaustion;EZH2 gene;FDA approved;Flow Cytometry;Funding;Goals;Growth;Health;hearing impairment;High Dose Chemotherapy;high risk;Human;Immune;Immune Targeting;immunoregulation;Immunotherapeutic agent;Immunotherapy;improved;improved outcome;In Vitro;in vivo;Infertility;inhibitor;insight;Intrinsic factor;JUN gene;Knowledge;Laboratories;Late Effects;LCP2 gene;Left;Link;Long-Term Effects;Macrophage;Malignant Childhood Neoplasm;Malignant Neoplasms;Membrane;Mesenchymal;Mission;Modeling;Monoclonal Antibodies;mouse model;Natural Killer Cells;NCAM1 gene;neoplastic cell;Neural Cell Adhesion Molecule L1;Neuroblastoma;neuroblastoma cell;next generation;novel;novel therapeutics;overexpression;patient derived xenograft model;Patient-Focused Outcomes;Patients;Performance;Pharmaceutical Preparations;prevent;programs;Public Health;receptor;Regimen;Regulation;Relapse;relapse patients;Research;Resistance;resistance mechanism;response;Risk;Role;Sampling;Second Primary Cancers;Signal Transduction;Specificity;standard of care;success;Surface;Surface Antigens;Survivors;T cell differentiation;T-Cell Receptor;T-Lymphocyte;Testing;Therapeutic;therapeutically effective;tumor;tumor microenvironment;United States National Institutes of Health;Work

PROJECT_TITLE: Leveraging biological insights to enhance immunotherapies


NIH_SPENDING_CATS: Cancer;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: CORE A NARRATIVE Core A is aligned to the public health mission of the National Institutes of Health as it provides the scientific, budgetary, and administrative leadership necessary to continue to achieve the ambitious goal of improving neuroblastoma patient outcomes through this Program. This translational research Program focused on neuroblastoma will continue to provide insights relevant to the broader fields of both pediatric and medical oncology.

PROJECT_TERMS: Address;anti-cancer research;Applications Grants;Articulation;biobank;Budgets;Child;Clinical Trials;clinically relevant;Collaborations;Complex;Critiques;Department chair;Development;European;experience;Generations;Goals;high risk;improved;improved outcome;Infrastructure;insight;Institution;Investigation;Lead;Leadership;Malignant Childhood Neoplasm;Medical Oncology;member;Mentors;Mission;multidisciplinary;Neuroblastoma;novel strategies;Occupational activity of managing finances;Oncology;pandemic disease;Pathology;Patient-Focused Outcomes;Patients;Pediatric Oncology;Productivity;Program Research Project Grants;programs;Public Health;rational design;recruit;Reporting;Reproducibility;Research;Research Personnel;Research Priority;Research Project Grants;Resistance;responsible research conduct;Retirement;Saint Jude Children's Research Hospital;Science;Site;Structure;Testing;Therapy Clinical Trials;therapy design;Time;Toxic effect;translational goal;Translational Research;translational research program;Translations;United States National Institutes of Health


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

PHR: CORE B NARRATIVE Core B is essential to the public health relevance and alignment to NIH mission of this Program as it will provide the translational output of the laboratory-based Projects into early phase clinical trials and provide the infrastructure for the correlative studies, biomarkers, and unique resistant tumor specimens necessary for Project Investigators to achieve the goal of improving neuroblastoma patient outcomes.

PI_NAMEs: PARK, JULIE R (contact)

PROJECT_TERMS: Acceleration;Address;Advisory Committees;bench-to-bedside translation;biobank;Biocompatible Materials;Biological;Biological Markers;Biology;biomarker development;Biometry;Blood;Bone Marrow;Budgets;Cancer Center;chemotherapy;Child;Childhood Solid Neoplasm;Clinic;Clinical;clinical care;Clinical Data;clinical database;clinical material;Clinical Research;Clinical Trials;Collaborations;Combination immunotherapy;Combined Modality Therapy;Communication;Complex;Conduct Clinical Trials;Contracts;Correlative Study;Data;data quality;Databases;Dedications;design;Development;Differentiation Therapy;Disease;Dose;early phase clinical trial;early phase trial;Electronics;Eligibility Determination;Enrollment;Ensure;Evaluation;Evolution;experience;forging;Funding;Future;Genetic;Genomics;Geography;Goals;high risk;high standard;Image;image archival system;Immune system;Immuno-Chemotherapy;Immunologic Markers;Immunotherapeutic agent;Immunotherapy;improved;improved outcome;individualized medicine;Industry;Infrastructure;inhibitor;innovation;International;Laboratories;Laboratory Research;Leadership;Licensure;Link;metaiodobenzylguanidine;Mission;Molecular;Molecular Abnormality;Molecular Profiling;Monitor;Myeloablative Chemotherapy;Neuroblastoma;new therapeutic target;Newly Diagnosed;Normal tissue morphology;novel;novel strategies;novel therapeutics;operation;Operative Surgical Procedures;Outcome;Output;Parents;Pathology;patient biomarkers;Patient Selection;Patient-Focused Outcomes;Patients;Phase;phase 3 testing;Phase III Clinical Trials;Play;precision medicine;preclinical trial;predictive marker;Probability;programs;Protocols documentation;public health relevance;Publications;Radiation therapy;radiological imaging;Radiopharmaceuticals;randomized trial;Refractory;Relapse;relapse patients;Reporting;Research Personnel;Resistance;Resources;response;response biomarker;Role;Safety;Sampling;Secure;Series;Site;Specimen;success;Summary Reports;targeted treatment;Testing;Therapeutic;therapy resistant;Time;Tissue Banks;Toxic effect;Translating;translational goal;Translations;trial design;tumor;tumor heterogeneity;tumor microenvironment;Tumor Tissue;tumorigenesis;United States Food and Drug Administration;United States National Institutes of Health

PROJECT_TITLE: Translational, statistical, and clinical trials core


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: PROJECT NARRATIVE Nearly all aspects of biology and human disease are rooted in gene regulation. Our knowledge and abilities to understand, control, and rectify gene expression and mis-expression is fundamental to basic biological knowledge and medicine. We propose a continuation of our successful predoctoral training program to prepare a cadre of young scientists who excel in cross-disciplinary skills and address fundamental questions related to gene regulation processes and their impact on human health.

PI_NAMEs: REESE, JOSEPH C (contact)

PROGRAM_OFFICER_NAME: BROWN, ANISSA F

PROJECT_TERMS: Gene Expression Regulation;Training Programs

PROJECT_TITLE: Eukaryotic Gene Regulation (EGR) Training Program

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Hematology

ORG_CITY: MILWAUKEE

ORG_NAME: VERSITI WISCONSIN, INC.

ORG_STATE: WI

PHR: PROJECT NARRATIVE Transfusion Medicine, Classical Hematology, and Glycobiology are increasingly important, but under- subscribed, areas of medicine. We propose a new and comprehensive training program for trainees in these areas of research to become independent scientists who will pursue careers that advance science to improve the health of millions of people with blood disorders.

PI_NAMEs: HOFFMEISTER, KARIN MARIA;MAST, ALAN E (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TITLE: Training in Transfusion Medicine and Classical Hematology


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The Training Program in Basic Immunology at Washington University in Saint Louis seeks continued support (Years 46-50) to maintain a highly successful mechanism to support talented predoctoral and postdoctoral trainees, who aspire to become leaders in immunology research. The program faculty are highly accomplished scientists performing state-of-the-art immunology research in a premier world-class medical research institution. The Program has supported the careers of many of today's most successful immunology researchers, and its continued support will train future leaders to expand our understanding of fundamental immunological mechanisms, with implications for major human diseases.

PI_NAMEs: MURPHY, KENNETH M (contact);RAVICHANDRAN, KODI S

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Immunology;Training Programs

PROJECT_TITLE: Training Program in Basic Immunology

STUDY_SECTION: AITC

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


ORG_CITY: BALTIMORE

ORG_DEPT: ORTHOPEDICS

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Chronic pain is the most prominent symptom of osteoarthritis (OA) that profoundly affects the quality of life and daily physical activity of the patients. In the proposed project, we will examine whether enlargement of subchondral bone cavity promote sensory innervation and sensitization of the nociceptive nervous system. Importantly, we will validate whether abnormal bone remodeling induced enlargement of subchondral bone cavity is a novel treatment target for OA pain.

PI_NAMEs: CAO, XU  (contact);GUAN, YUN

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Affect;afferent nerve;Afferent Neurons;Alendronate;Arachidonic Acids;axon growth;axon guidance;bisphosphonate;Blood Vessels;bone;Bone Density;Bone Growth;Bone Marrow;bone mass;Bone Pain;Bone remodeling;Bone Resorption;Bone structure;Cartilage;Cell Aging;Cell Cycle Arrest;Cell Lineage;Cell secretion;Cells;chronic pain;Clinic;conditional knockout;Coupled;Coupling;Coxibs;cyclooxygenase 2;Data;Data Set;Degenerative polyarthritis;Deterioration;Development;Dinoprostone;disability;Disease;Dose;driving force;Edema;Equilibrium;experience;Fiber;functional decline;Future;Generations;inhibitor;Joints;knee pain;Knock-out;Knockout Mice;Lesion;Ligaments;Magnetic Resonance Imaging;Mediating;Medical;medical attention;Meniscus structure of joint;Mobility decline;Mus;Nerve;nerve supply;Nervous System;Neurons;Nociception;Nociceptors;novel;NTN1 gene;osteoarthritis pain;Osteoblasts;Osteoclasts;Osteogenesis;Osteoporosis;osteoporotic bone;Pain;pain relief;Pathogenesis;Patients;Peripheral Nervous System;Persistent pain;Persons;Pharmaceutical Preparations;Physical activity;Production;Quality of life;receptor;Regulation;Reporting;Rest;Risk Factors;Role;senescence;senescence associated secretory phenotype;senescent cell;senolytics;Sensory;small molecule;Source;subchondral bone;Symptoms;Synovial Membrane;Synovitis;Testing;Thinness;Tissues;Transforming Growth Factor beta;United States National Institutes of Health;Visualization;WFDC2 gene;Zoledronic Acid

PROJECT_TITLE: Subchondral Bone Cavities in Osteoarthritis Pain


NIH_SPENDING_CATS: Cancer

PHR: PROJECT NARRATIVE Surgeon-scientists are in a unique position to facilitate the clinical translation of basic science and clinical effectiveness research discoveries, with the potential for significant improvements in patient care. The Surgical Oncology Basic Science and Translational Research Training Program will provide a diverse cadre of surgical trainees from general surgery and other surgical subspecialties the opportunity to develop essential skill sets in basic science, translational, public health and disparities research.

PI_NAMEs: EBERLEIN, TIMOTHY J;GILLANDERS, WILLIAM E. (contact);TORIOLA, ADETUNJI T

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Basic Science;Surgical Oncology;Training Programs;Translational Research

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Institutional Training and Education Study Section (F)[NCI-F]


ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: PROJECT NARRATIVE Lung diseases, such as those caused by gene mutations, result in significant morbidity and mortality worldwide. The advent of stem cell discoveries and regenerative medicine presents new opportunities to improve our understanding of these diseases and to develop new treatment approaches. Here we propose a Program Project Grant, composed of 4 integrated projects and 2 cores, whose goal is advancing the latest discoveries in stem cell biology, human organoid culture models, and gene editing to better understand and develop new treatments for genetic lung diseases.

PI_NAMEs: KOTTON, DARRELL N. (contact)

PROGRAM_OFFICER_NAME: LIN, SARA

PROJECT_TERMS: Address;Affect;Airway Disease;airway epithelium;Alveolar;alveolar epithelium;Alveolus;Area;Automobile Driving;Basal Cell;Basic Science;Biomedical Research;Blood Vessels;cell bank;Cell Compartmentation;Cell Therapy;Cells;Clinical;clinical application;clinical translation;Congresses;Disease;Distal;Engraftment;Epithelial Cells;epithelial stem cell;Epithelium;experimental study;Face;Foundations;Frustration;Functional disorder;Funding;Future;gain of function;Gene Mutation;Genes;Genetic;Genetic Diseases;Genetic Models;Goals;Health;Human;human induced pluripotent stem cells;human model;improved;In Vitro;in vivo;induced pluripotent stem cell;Inherited;Interruption;Lead;Life;Literature;Lung;Lung Capacity;Lung Diseases;Mesenchymal;Metabolic;Methods;Mission;mitochondrial dysfunction;Modeling;Morbidity - disease rate;mortality;Mutation;Natural regeneration;Nobel Prize;novel;novel therapeutic intervention;nuclear reprogramming;Organoids;Pathogenicity;Pathway interactions;patient derived induced pluripotent stem cells;Phenotype;Pluripotent Stem Cells;Precision therapeutics;Primary Ciliary Dyskinesias;Program Research Project Grants;programs;proteostasis;Protocols documentation;Publishing;reconstitution;regenerative cell;Regenerative Medicine;regenerative therapy;repaired;Research;Research Personnel;Resource Sharing;Resources;Solid;stem cell based approach;stem cell biology;stem cell model;stem cell population;Stem Cell Research;stem cells;Strategic Planning;Structure of parenchyma of lung;success;symptom treatment;Technology;Therapeutic;therapeutic development;Time;tissue stem cells;Translating;Translations;Transplantation;Work

PROJECT_TITLE: Developing Pluripotent Stem Cells to Model and Treat Lung Disease


NIH_SPENDING_CATS: Lung;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PROJECT_TERMS: Agreement;Alveolar Cell;Alveolus;Applications Grants;Archives;Automobile Driving;Bioinformatics;Boston;Catalogs;Cell Line;Cells;cohesion;Communication;Communities;Complex;cost effectiveness;Cost efficiency;Data Set;Databases;design;Disputes;Ensure;Funding;Future;gene editing technology;Genes;Genetic;Goals;Group Meetings;Home;induced pluripotent stem cell;Information Dissemination;Infrastructure;Laboratories;Lead;Location;Logistics;Lung;Lung Diseases;meetings;member;Methods;Mission;Modeling;Monitor;National Heart, Lung, and Blood Institute;novel therapeutics;Occupational activity of managing finances;Office of Administrative Management;operation;Operations Research;Performance;Pluripotent Stem Cells;Principal Investigator;Procedures;Process;Productivity;Program Research Project Grants;programs;Protocols documentation;Publications;Quality Control;Regenerative Medicine;Reporting;Research;Resolution;Resources;Schedule;Services;social media;sound;stem cell based approach;stem cells;Structure;success;symposium;synergism;Therapeutic;Training and Education;Training Programs;United States National Institutes of Health;Universities;vector;Work;working group

PROJECT_TITLE: Adminstrative Core


NIH_SPENDING_CATS: Genetics;Lung;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PI_NAMEs: WILSON, ANDREW A (contact)

PROJECT_TERMS: Award;Basal Cell;biobank;Biological Assay;Boston;cell bank;Cell Line;cell repository;Cell Reprogramming;cell type;Cells;Cloning;Country;CRISPR interference;CRISPR-mediated transcriptional activation;Disease;disease model;Ensure;experience;Experimental Models;experimental study;Faculty;Framingham Heart Study;Funding;Future;G-Banding;gene editing technology;Gene Expression;gene-editing approach;Generations;Genes;Genetic;Genetic Fingerprintings;Guide RNA;Individual;induced pluripotent stem cell;innovation;interest;Joints;Karyotype;Karyotype determination procedure;knock-down;Knock-in;Label;Laboratories;Lentivirus;Letters;Lung;Lung Diseases;Measures;medical schools;Modeling;Mutation;mutation correction;National Center for Advancing Translational Sciences;National Heart, Lung, and Blood Institute;Output;overexpression;Participant;Pathway interactions;Patients;Peripheral Blood Mononuclear Cell;pluripotency;pluripotent stem cell differentiation;Pluripotent Stem Cells;Population;Program Research Project Grants;Protocols documentation;Quality Control;R24;Reagent;repository;Research Personnel;Resource Sharing;Science;Services;Standardization;stem cell genes;synergism;Technology;Testing;Time;Tissues;tool;transcription factor;Transcription Initiation Site;United States National Institutes of Health;Universities;Variant;Viral;volunteer;Work

PROJECT_TITLE: iPSC Gene Editing Core


NIH_SPENDING_CATS: Biotechnology;Genetics;Lung;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

PROJECT_TERMS: ABCA3 gene;Activities of Daily Living;Address;airway epithelium;Alveolar;Alveolar Cell;alveolar epithelium;Alveolus;antagonist;Autologous;Basal Cell;Biological Assay;Biology;Blood;Cell Compartmentation;Cell Differentiation process;Cell Line;Cell Physiology;Cell Therapy;cell type;Cells;Childhood;Collaborations;Data;directed differentiation;Disease;disease-causing mutation;Distal;Engineering;Engraftment;Epithelial Cells;epithelial stem cell;Epithelium;Functional disorder;Future;gene correction;gene editing technology;Genes;Genetic;Genetic Models;Goals;Head;Hematopoietic Stem Cell Research;Human;human induced pluripotent stem cells;Immunocompetent;Immunosuppression;in vivo;in vivo engraftment;induced pluripotent stem cell;Interstitial Lung Diseases;Isogenic transplantation;Lung;Lung Diseases;Methods;Modeling;Motility;mouse genetics;mouse model;Mus;Mutation;Normal Cell;novel;patient derived induced pluripotent stem cells;Patients;Phenotype;pluripotent stem cell differentiation;Pluripotent Stem Cells;Population;pre-clinical;Primary Ciliary Dyskinesias;progenitor;Publishing;reconstitution;regeneration function;self-renewal;Seminal;Signal Transduction;simulation;stem cell function;stem cell niche;stem cells;surfactant;Techniques;Testing;Tissues;translational potential;Translations;Transplantation;Work

PROJECT_TITLE: Engraftment of PSC-Derived Lung Lineages to Reconstitute in vivo Airway and Alveolar Stem Cell Function


NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Digestive Diseases;Emphysema;Genetics;Liver Disease;Lung;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PROJECT_TERMS: Acceleration;Address;Affect;Alleles;alpha 1-Antitrypsin;alpha 1-Antitrypsin Deficiency;Alveolar;alveolar epithelium;analog;Animals;Biological Models;cell injury;Cell Line;Cell Lineage;Cell Physiology;cell type;Cells;Cessation of life;Chronic Obstructive Pulmonary Disease;cigarette smoke;Clinical;Data;Deficiency Diseases;Derivation procedure;design;Disease;disease model;endoplasmic reticulum stress;Engineering;Epithelial Cells;Epithelium;experience;experimental study;exposure to cigarette smoke;gain of function;Genes;Genetic Transcription;genome editing;Genotype;Goals;Hepatocyte;hepatocyte injury;Hepatotoxicity;Human;human induced pluripotent stem cells;human model;Immune;Impairment;improved;in vivo;Individual;induced pluripotent stem cell;Inherited;Injury;Intravenous infusion procedures;Liquid substance;Liver;Longitudinal cohort;loss of function;Lung;Lung Diseases;lung injury;Lung Transplantation;Metabolic dysfunction;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;mutant;Mutation;National Heart, Lung, and Blood Institute;novel;Participant;Pathogenesis;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Peptide Hydrolases;Phenotype;Plasma;Pluripotent Stem Cells;Population;Predisposition;Production;Protease Inhibitor;protein aggregation;protein expression;Proteins;Publishing;Pulmonary Emphysema;pulmonary function;pulmonary function decline;Pulmonary Function Test/Forced Expiratory Volume 1;Reagent;response;Sampling;single-cell RNA sequencing;Smoke;standard of care;stem cell function;stem cell model;stem cells;Structure of parenchyma of lung;Testing;Therapeutic;Time;tool;Toxic effect;Transcript;transcriptome;Treatment Efficacy;treatment strategy

PROJECT_TITLE: Elucidating the contribution of lung epithelial gain of function toxicity to AATD disease pathogenesis