ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

ORG_CITY: ANN ARBOR

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative The MICHR Translational Science Immersion program (MICHR-TSI) is designed to increase diversity in the biomedical research workforce. Key to this new R25 program is multi-level mentoring and hands-on research experience designed to expose participants to research practice and inspire them to pursue further training focused on eliminating health disparities and improving health care quality. The MICHR-TSI will provide greater training inlets to MICHR and U-M, such that we will build and retain a strong pipeline of next-generation translational researchers.

PI_NAMEs: ELLINGROD, VICKI L;WOOLFORD, SUSAN  (contact)

PROGRAM_OFFICER_NAME: KRASNOVA, IRINA N

PROJECT_TERMS: Accountability;Active Learning;Area;Behavioral Research;Biomedical Research;Black race;career;Career Choice;career development;career networking;Characteristics;Clinical;Clinical and Translational Science Awards;Clinical Sciences;cohort;Communication;Communications Media;Communities;Competence;Degree program;design;Economics;Education;Education Projects;Educational Curriculum;Eligibility Determination;Enrollment;Equity;equity, diversity, and inclusion;Exercise;experience;Exposure to;faculty mentor;Feedback;Female;flexibility;Foundations;Goals;graduate student;hands on research;Health;health care quality;Health Disparities Research;health disparity;Health Occupations;Health Professional;Hispanic;Historically Black Colleges and Universities;Hour;Immersion;improved;Individual;Information Sciences;Instruction;interest;Latinx;Leadership;Learning;Maps;massive open online courses;Master of Science;member;Mentored Clinical Scientist Development Program;Mentors;Mentorship;Michigan;Minority-Serving Institution;multi-racial;next generation;Oral;Outcome;Participant;peer;performing art;Phase;Play;pre-doctoral;Precision Health;Preparation;Process;Program Development;programs;Research;Research Project Grants;research to practice;Research Training;Resources;responsible research conduct;Role;Science;science education;Series;skills;social;social media;Social Network;Structure;Students;summer research;Time;TNFSF15 gene;Training;translational health science;Translational Research;translational scientist;Trust;undergraduate student;United States;United States National Institutes of Health;Universities;Visual;Work;Writing

PROJECT_TITLE: MICHR-Translational Science Immersion (MICHR-TSI)

STUDY_SECTION_NAME: Special Emphasis Panel[ZTR1 CI-6 (01)]


ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: RICHMOND

ORG_COUNTRY: UNITED STATES

ORG_DEPT: GENETICS

ORG_FIPS: US

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE Taking discoveries in the laboratory and using them to improve human health requires researchers specifically trained to work collaboratively with other scientists as well as with patients, caregivers, clinicians, and other healthcare stakeholders. Knowing diversity enhances research training environments and is necessary to address the most complex, translational problems, Virginia Commonwealth University’s Translational Biomedical Sciences (TBS) Predoctoral Training Program will give special attention to including program trainees from backgrounds underrepresented in the biomedical sciences. It is within this context that the TBS Program will train a diverse group of scientists with specific knowledge, skills, and abilities to conduct research that will have a meaningful impact on human health.

PI_NAMEs: MOSAVEL, MAGHBOEBA ;NEIGH, GRETCHEN N;SARKAR, DEVANAND  (contact)

PROGRAM_OFFICER_NAME: DIBELLO, ANTHONY THOMAS

PROJECT_TERMS: pre-doctoral;Universities;Virginia

PROJECT_TITLE: CTSA Predoctoral T32 at Virginia Commonwealth University


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Diabetes;Osteoporosis

ORG_CITY: MADISON

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE One component of the proposed research focuses on signal transduction by a set of cell-surface receptors that play crucial roles in human physiology and are targets of peptide-based drugs. The other focus involves liquid-liquid phase separation (LLPS), a unique form of biomolecular assembly that occurs within living cells but can go awry to cause disease. For both phenomena, we pursue unique molecular-level experimental designs to gain fundamental insights that could provide a foundation for new therapeutic strategies.

PI_NAMEs: GELLMAN, SAMUEL H. (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Address;Agonist;alpha helix;Biopolymers;Cell Physiology;Cell Surface Receptors;Cells;chemical synthesis;design;Diabetes Mellitus;Disease;dynamical evolution;Evaluation;Experimental Designs;Family;Foundations;Future;G-Protein-Coupled Receptors;GLP-2R;Glucagon;Glucagon Receptor;glucagon-like peptide 1;Goals;Human;human disease;Hypoglycemia;insight;Liquid substance;Mediating;Medicine;Membrane;Modeling;Molecular;Molecular Conformation;Neurodegenerative Disorders;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutic intervention;Organelles;Osteoporosis;Outcome;Parathyroid Hormone Receptor;Patients;peptide drug;Peptides;Phase;Physiology;Play;polypeptide;Polypeptide Hormones;Process;Proteins;receptor;receptor binding;Research;RNA;Role;Shock;Short Bowel Syndrome;Signal Transduction;Testing;Therapeutic;Transcend;Work

PROJECT_TITLE: Processes mediated by polypeptides

STUDY_SECTION: MRAE

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - E Study Section[MRAE]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Clinical Research;Immunization;Infectious Diseases;Malaria;Malaria Vaccine;Orphan Drug;Pediatric;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE Malaria causes 247 million cases and 619,000 deaths annually. Successful development and deployment of a highly efficacious malaria vaccine that achieves the World Health Organization target of >90% efficacy would both reduce malaria morbidity and mortality and accelerate malaria eradication efforts. The proposed research seeks to plan for a two-part clinical trial of the PfSPZ-LARC2 vaccine in a highly endemic area of Burkina Faso.

PI_NAMEs: LAURENS, MATTHEW BRENT (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: Acceleration;Adolescent;Adult;Africa;Age;Age Months;Anti-malarials;Area;Attenuated;Beds;Blood;Budgets;Burkina Faso;Case Report Form;Cessation of life;Characteristics;Child;Clinical;Clinical assessments;clinical development;clinical trial protocol;Clinical Trials;Consent Forms;Country;Cyclic GMP;Data;data management;Development;Dose;efficacy testing;experience;Generations;Genes;Germany;Goals;Hospitalization;Human;Immune response;immunogenicity;Individual;Infant;Infection;Infection prevention;Insecticides;Intervention;Investments;Malaria;malaria infection;malaria transmission;Malaria Vaccines;Mali;Manuals;manufacture;Measures;Monitor;Morbidity - disease rate;mortality;Parasites;Plasmodium falciparum;Plasmodium falciparum vaccine;prevent;Procedures;programs;Protocols documentation;Publishing;Radiation;Research;Residual state;Safety;Seasons;side effect;Sporozoite vaccine;Tanzania;Testing;Time;Training;transmission blocking;transmission process;Vaccination;vaccine efficacy;vaccine evaluation;Vaccines;World Health Organization

PROJECT_TITLE: Safety, immunogencity, and efficacy of PfSPZ LARC2 malaria vaccine in malaria-exposed adults and children

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 SAS-M (S1)]


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

ORG_CITY: Newark

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative: The New Jersey Alliance for Clinical and Translational Science (NJ ACTS), a partnership among four institutions, Rutgers, Princeton, the New Jersey Institute for Technology, and RWJBarnabas Health has profoundly altered the trajectory of clinical and translational science (CTS) across New Jersey. NJ ACTS now seeks to advance CTS further by developing, demonstrating, and disseminating best-in-class processes and providing infrastructure, services, and training that incorporate and advance team science, diversity and inclusion, health policy, and a learning health system. By moving discoveries to practice to policy, we hope to improve health, reduce inequities, and hope to understand why some, but not, all people acquire a disease or respond to therapy.

PI_NAMEs: PANETTIERI, REYNOLD ALEXANDER (contact)

PROGRAM_OFFICER_NAME: GANNOT, GALLYA

PROJECT_TERMS: Academia;Academy;Acceleration;Achievement;Address;Adoption;Area;Assessment tool;career;career development;Clinical Research;Clinical Sciences;Clinical Trials;Cohort Studies;Communities;community collaboration;community engagement;Competence;cost;Data;data warehouse;Databases;digital;Disease;disease heterogeneity;Disparate;dissemination science;Diverse Workforce;diversity and inclusion;Ecosystem;Education;Elements;equity, diversity, and inclusion;Ethnic Population;Evaluation;evidence base;experience;Faculty;Feedback;Fostering;Foundations;Funding;Genus Mentha;Goals;Government;Health;health care delivery;health disparity;health equity;health equity promotion;Health Policy;Health system;Image;implementation science;improved;Individual;Industry;Inequity;Informatics;Infrastructure;innovation;Institution;interdisciplinary approach;Intervention;Learning;Logistics;Mentored Clinical Scientist Development Program;Mentors;Mission;Neighborhoods;New Jersey;next generation;novel strategies;pandemic disease;Participant;Patients;Performance;Persons;Policies;Policy Maker;Population;population health;Process;programs;Provider;Qualifying;racial population;Recommendation;recruit;Research;Research Personnel;Resources;Safety;Science;science teacher;Services;Solid;Students;success;Technology;Testing;Time;tool;Training;Training and Education;Training Programs;Translating;translational progress;Translational Research;translational scientist;Translations;treatment response;Universities;Vision;Work;Workforce Development

PROJECT_TITLE: NJ ACTS: A Platform for Translational Science in New Jersey

STUDY_SECTION_NAME: Special Emphasis Panel[ZTR1 CI-9 (01)]


ORG_CITY: PITTSBURGH

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative Our research is focused on three lipid GPCRs in inflammation and the resolution of inflammation, which represent promising targets for developing new drugs for many inflammatory disorders. We take a variety of research strategies to elucidate the structural basis for receptor function and develop new agents targeting these receptors as novel pharmacological tools. The discoveries from our research will advance our understanding of inflammation biology and facilitate the development of new drugs for controlling inflammation in numerous diseases.

PI_NAMEs: ZHANG, CHENG  (contact)

PROJECT_TERMS: Address;Agonist;antagonist;Biology;C5a anaphylatoxin receptor;Cell membrane;Chemicals;CMKLR1 gene;Complex;Computational Biology;Cryoelectron Microscopy;Development;Disease;Dopamine D2 Receptor;drug candidate;Drug Controls;Family;Fatty Acids;fMet-Leu-Phe receptor;FPR2 gene;Funding;Future;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;GPR32 gene;GPR84 gene;Inflammation;Inflammatory;Inflammatory Response;interest;Ligands;Lipids;Macrophage;Mediator;Medium chain fatty acid;member;Molecular;Molecular Conformation;New Agents;novel;novel therapeutics;Omega-3 Fatty Acids;Peptides;Phagocytosis;Pharmaceutical Preparations;pharmacologic;Pharmacology;Process;Property;Prostaglandin D2;receptor;receptor binding;receptor function;Research;Resolution;Signal Transduction;Signaling Molecule;small molecule;structural biology;Structure;targeted agent;tool

PROJECT_TITLE: Structure, pharmacology and signaling of G protein-coupled receptors (GPCRs) in inflammation


NIH_SPENDING_CATS: Bioengineering;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: CLEMSON

ORG_DEPT: PHYSICS

ORG_NAME: CLEMSON UNIVERSITY

ORG_STATE: SC

PHR: Project narrative Electrostatic interactions and the corresponding electrostatic energy components are essential for the function, stability, and interactions of virtually all biological macromolecules, nanoparticles, and substrates. Thus, further development and maintenance of the DelPhi package and associated resources will be beneficial for the biomedical community in its efforts to reveal the molecular effects of human genetic disorders. Revealing molecular effect of disease-causing mutations facilitates early assessment of disease risk and development of therapeutic solutions.

PI_NAMEs: ALEXOV, EMIL GEORGIEV (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Amino Acids;Area;Binding;Bioinformatics;Biological;Biophysics;Collaborations;Communities;Computer software;Consensus;Databases;density;Development;Disease;disease-causing mutation;disorder risk;DNA;Electrostatics;Entropy;Event;Free Energy;Genetic Diseases;Human;Human Genetics;interest;Investigation;laboratory experiment;Machine Learning;machine learning method;macromolecule;Maintenance;MAP Kinase Gene;Methods;Missense Mutation;Modeling;Molecular;Molecular Biology;Molecular Conformation;molecular modeling;Mutation;nanoparticle;novel;Pathogenicity;prediction algorithm;Process;Proteins;protonation;Research;Resources;RNA;Schedule;structural biology;symposium;therapeutic development;Training;virtual;web server

PROJECT_TITLE: DelPhi and associated resources: maintenance, development and applications


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Genetics;Human Genome;Immunization;Infectious Diseases;Influenza;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative In this proposal we intend to comprehensively analyze the frequencies and single cell genomic states of circulating Tfh and activated B cells that were induced by the flu vaccine in a unique pediatric cohort which involved longitudinal analysis of antibody responses. These analyses will be complemented with high dimensional cytokine profiling and the use of an in vitro culture systems. In doing so, we will test the hypothesis that cellular properties and molecular features of Tfh and B cells, the latter revealed by regulatory genomics and machine learning, which are reflective of vigorous and sustained GC B cell responses will be predictive of and underlie durable high affinity antibody responses.

PI_NAMEs: ALCORN, JOHN F;DAS, JISHNU ;SINGH, HARINDER  (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: Affinity;Age;aged;Algorithms;Antibodies;Antibody Affinity;Antibody Response;Antibody titer measurement;antibody-mediated rejection;B-Cell Activation;B-Lymphocytes;Biological Assay;Blood;Bone Marrow;CD4 Positive T Lymphocytes;Cell Communication;Cells;Cessation of life;Child;Clinical Trials;Clone Cells;cohort;COVID-19 pandemic;cytokine;Cytokine Signaling;Data Set;design;Disease;Drops;Elasticity;explainable machine learning;Frequencies;gene network;Generations;Genes;Genetic Transcription;genomic data;genomic profiles;genomic profiling;Genomics;Health;Helper-Inducer T-Lymphocyte;Hemagglutinin;high dimensionality;Human;human data;Immune;Immunoglobulin Somatic Hypermutation;Immunology;In Vitro;Influenza;influenza infection;Influenza prevention;Influenza vaccination;influenza virus vaccine;interdisciplinary collaboration;Kidney Transplantation;Lasso;longitudinal analysis;Machine Learning;machine learning algorithm;machine learning prediction algorithm;Measures;Memory B-Lymphocyte;Molecular;mouse model;multimodality;multiple omics;Mus;novel;Participant;Pediatric cohort;Peripheral Blood Mononuclear Cell;Phase;Plasma Cells;Predisposition;Property;Recommendation;Research;response;Sampling;seasonal influenza;seroconversion;Serum;severe COVID-19;single cell analysis;single cell ATAC-seq;single cell genomics;single-cell RNA sequencing;Structure of germinal center of lymph node;System;T-Lymphocyte;Testing;Time;United States;Vaccination;vaccine effectiveness;Vaccinee;Vaccines;vaccinology;Virus;young adult

PROJECT_TITLE: B and Tfh cell dynamics underlying durable antibody responses to flu vaccine in children

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 JTS-I (S1)]


NIH_SPENDING_CATS: Asthma;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Lung;Pediatric;Prevention

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Prevention of asthma is a pressing, unmet need of utmost priority and this trial will test whether treatment of high-risk children with allergy and wheeze with omalizumab (anti-IgE), an intervention directed towards IgE, will prevent and alter asthma progression 2 years after 2 years treatment of therapy. This project will allow us to complete the trial and use state of the art epigenomic and transcriptomic techniques with integrated techniques to examine the role of specific alterations in anti-viral and immunologic responses in transducing clinical responses seen in the trial. Regardless of the outcome is of the primary trial, this project will uncover novel mechanisms affecting the development of asthma and allergic diseases.

PI_NAMEs: PHIPATANAKUL, WANDA  (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: 3 year old;Affect;Aftercare;Allergen Immunotherapy;Allergens;Allergic;Allergic Disease;anti-IgE;Anti-viral Response;antigen-specific T cells;Asthma;asthma prevention;Blood;Cells;Cellular Structures;Child;Childhood;Childhood Asthma;Chronic Disease;Clinical;Clinical Data;clinical effect;clinical phenotype;clinical predictors;Clinical Treatment;cohort;COVID-19 pandemic;Data;Data Set;Development;Disease;disorder prevention;DNA Methylation;double-blind placebo controlled trial;Enrollment;environmental allergen;Epigenetic Process;epigenomics;Epithelial Cells;Epithelium;follow-up;Functional disorder;Funding;Gene Expression;Gene Expression Profiling;gene network;Genetic Transcription;Grant;Heterogeneity;high risk;Hypersensitivity;IgE;Immune response;Immune Tolerance;Immunity;Immunologics;improved;Individual;Inflammation;Inflammatory;insight;Interferon alpha;Intervention;Knowledge;Mediating;Molecular;Mucous Membrane;Multiomic Data;Nasal Epithelium;Natural History;Nose;novel;omalizumab;Outcome;Outcome Study;Pathway Analysis;Pathway interactions;Patients;Phase;Play;Population;potential biomarker;Predisposition;prevent;Prevention;primary outcome;Process;Randomized;Recurrence;Regulatory T-Lymphocyte;Resolution;respiratory;response;restoration;Role;Sampling;Severities;Severity of illness;Source;System;T-Lymphocyte;Techniques;Testing;Time;transcriptome;transcriptomics;treatment effect;Viral;Virus Diseases;Wheezing

PROJECT_TITLE: Controlling and Preventing Asthma Progression and Severity in Kids with Omalizumab Extension (PARK-EXT)

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 KGH-I (S1)]


NIH_SPENDING_CATS: Machine Learning and Artificial Intelligence

ORG_CITY: EAST LANSING

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: Most biological function takes place inside cells. This research aims at understanding the fundamental principles at the molecular level for how cellular environments shape biological function and disease. Understanding how cellular environments alter biomolecular behavior will furthermore inform more effective rational design strategies to identify new therapies targeting a variety of diseases.

PI_NAMEs: FEIG, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Address;Behavior;Biological;Biological Process;Cells;Collaborations;Complement;computerized tools;Cytoplasm;Disease;Drug Design;Environment;Enzymes;experimental study;Goals;insight;Liquid substance;Machine Learning;Membrane;Modeling;models and simulation;Molecular;multi-scale modeling;new therapeutic target;novel;Phase;Physical condensation;Protocols documentation;rational design;Research;Shapes;Structure;System;tool;Work

PROJECT_TITLE: Modeling and dynamics of biomolecules on cellular scales

STUDY_SECTION: MRAB

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Clinical Research;Comparative Effectiveness Research;Emerging Infectious Diseases;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative Isoniazid-monoresistant (IMR) tuberculosis (TB) comprises 1.1 million (11%) of the estimated 10 million new TB cases annually. The proposed R34 NIAID Clinical Trial Planning Grant will plan an open-label, randomized, controlled Phase 2C clinical trial that leverages the latest advances in TB therapeutics to compare the efficacy and safety of two novel 4-month regimens, composed of approved drugs in proven backbones, against the 6- month standard of care recommended by the World Health Organization for IMR-TB. The proposed trial fills a critical and unmet need in IMR-TB drug development by investigating regimens that are congruent with priorities in the NIAID Strategic Plan for Tuberculosis Research, while addressing two research gaps identified by international and US-based guidelines development groups: the evaluation of new regimens specifically for IMR-TB in randomized controlled trials, and reduction of the duration of pyrazinamide in treatment regimens for IMR-TB.

PI_NAMEs: VELASQUEZ, GUSTAVO EDUARDO (contact)

PROGRAM_OFFICER_NAME: LAUGHON, BARBARA E

PROJECT_TERMS: Address;Adolescent;Adult;Adverse event;Award;Caring;Clinical Data;clinical trial protocol;Clinical Trials;Communities;comparative efficacy;Country;Data;Development;Documentation;Dose;Drug Controls;drug development;Drug Interactions;Drug Kinetics;Drug resistance;efficacy evaluation;Ethambutol;Evaluation;Evidence based treatment;Exhibits;experience;Funding;Future;Grant;Guidelines;High Prevalence;improved;individual patient;innovation;International;Intervention;isoniazid;Isoniazid resistance;Lasers;Learning;Leprosy;Levaquin;Linezolid;Liquid substance;Lung;Meta-Analysis;Moxifloxacin;mycobacterial;National Institute of Allergy and Infectious Disease;Newly Diagnosed;novel;open label;Participant;Peru;Peruvian;Pharmaceutical Preparations;Phase;phase 3 study;pre-clinical;Predisposition;Pulmonary Tuberculosis;Pyrazinamide;Randomized;Randomized Controlled Clinical Trials;Randomized, Controlled Trials;Recommendation;Regimen;Relapse;Research;Rifampicin resistance;Rifampin;Rifamycins;rifapentine;Role;Safety;Scientific Advances and Accomplishments;Sputum;standard of care;Strategic Planning;Testing;Therapeutic;Time;treatment arm;treatment duration;Treatment Failure;Treatment Protocols;trial planning;Tuberculosis;tuberculosis drugs;United States National Institutes of Health;Vertebral column;Vietnam;Vietnamese;World Health Organization

PROJECT_TITLE: A Phase 2C Randomized, Controlled, Open-Label Trial of Novel Shortened Regimens for the Treatment of Isoniazid-Monoresistant TB (IMR-TB)

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 CAB-M (S1)]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE The goal of this project is to elucidate fundamental knowledge of the link between three-dimensional genome organization and gene expression. This research will investigate the properties of cohesin complexes, identify and characterize novel cohesin-interacting proteins, and elucidate the role of cohesin-mediated DNA loops in regulation of transcription and chromatin state. This knowledge is critical for understanding human health and disease states linked to altered three-dimensional genome organization, such as developmental disorders and cancers.

PI_NAMEs: DOWEN, JILL  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: 3-Dimensional;Acute;Binding;Biochemical;Biological Assay;Biology;CCCTC-binding factor;Cell Differentiation process;Cells;Chromatin;Chromatin Loop;cohesin;Complex;Defect;developmental disease;Disease;embryonic stem cell;Enhancers;Epigenetic Process;experience;functional genomics;Gene Expression;Gene Expression Regulation;Genetic;Genetic Transcription;Genome;genome editing;Genomics;Goals;Health;histone modification;Human;interdisciplinary approach;Knowledge;Link;Malignant Neoplasms;Mediating;Molecular;novel;promoter;Property;Proteins;Proteomics;Research;Role;Site;small molecule;Technology;Testing;Transcriptional Regulation;Variant

PROJECT_TITLE: The role of genome folding in regulating gene expression and chromatin state

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MRAF-C (01)]


ORG_CITY: OXFORD

ORG_NAME: MIAMI UNIVERSITY OXFORD

ORG_STATE: OH

PHR: PROJECT NARRATIVE Structural and dynamic changes in response to binding events, catalysis, and posttranslational modifications can effect positive or negative regulation of protein activity and downstream function in relevant cellular pathways. These changes cause perturbations of protein quality control and antibiotic resistance pathways and lead to a diverse range of pathologies including infections, neurodegenerative disorders, cancers, ischemia reperfusion injury, and recessive hereditary cerebellar ataxias. The discovery of mechanistic details is crucial for advancing our fundamental understanding of how binding events, catalysis, and posttranslational modifications modulate protein structure, dynamics, and function.

PI_NAMEs: PAGE, RICHARD C (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Antibiotic Resistance;Antibiotics;Ataxia;Bacteria;beta-Lactamase;Binding;Biological;Catalysis;Cell Physiology;Cerebellar Ataxia;Client;Complex;Defect;Enzymes;Event;Heat Shock 70kD Protein Binding Protein;Heat shock proteins;Infection;Inherited;Knowledge;Malignant Neoplasms;Mediating;Methylation;misfolded protein;Modification;Molecular;Molecular Chaperones;Neurodegenerative Disorders;novel therapeutics;Outcome;Pathology;Pathway interactions;Pharmaceutical Preparations;Phosphorylation;Post-Translational Protein Processing;prevent;Process;Protein Dynamics;protein function;protein misfolding;protein structure;Proteins;Quality Control;rational design;Regulation;Reperfusion Injury;response;Role;Set protein;Signal Pathway;Structure;System;Triage;ubiquitin mediated proteasome degradation;ubiquitin-protein ligase;Ubiquitination

PROJECT_TITLE: Function and Pathway outcomes of Dynamic Protein Structures


ORG_DEPT: PHYSIOLOGY

PHR: PROJECT NARATIVE Cell migration is essential for many physiological processes such as wound healing, immune response, and morphogenesis, and plays a significant role in pathological processes such as cancer metastasis and cardiovascular disease, the two leading causes of death in the developed world. We propose to study cell migration using a multi-disciplinary approach involving molecular perturbations, cutting-edge microscopy and image analysis. These studies will directly contribute to understanding of disease states such as tumor metastasis, fibrosis, and cardiovascular disease, and to our understanding of normal physiological processes such as wound repair.

PI_NAMEs: BEAR, JAMES E (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Actins;active control;Architecture;Area;Biochemical;Biological Assay;Biological Process;Cardiovascular Diseases;Cause of Death;Cell Adhesion;cell motility;Cell Physiology;Cell Shape;Cells;Cellular biology;Characteristics;Clathrin;conditional knockout;Cues;Cytoskeleton;Data;Disease;Disseminated Malignant Neoplasm;Embryonic Development;Endocytosis;Environment;Equilibrium;Fibrosis;Genes;Grant;Image Analysis;Immune response;Integrins;interdisciplinary approach;Knockout Mice;Light;Mediating;Microscope;Microscopy;migration;Molecular;Morphogenesis;Motility;mouse model;Neoplasm Metastasis;optogenetics;Pathologic Processes;Pathway interactions;Physiological Processes;Play;Protein Tyrosine Kinase;Proteomics;Publishing;Regulation;response;Role;Signal Pathway;Testing;Traction;tumor;Work;wound healing

PROJECT_TITLE: Systematic Analysis of the Actin Cytoskeleton and Directed Cell Migration

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


ORG_CITY: PISCATAWAY

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

PHR: Project Narrative: RNA-mediated chromatin regulation and transgenerational epigenetic inheritance hold profound implications in genome-environment interaction and inheritance of gene activities relevant to development, aging, and disease. Using C. elegans as a model organism, our short-term research plan will characterize a new chromatin structure and a new mode of siRNA regulation that we have recently identified. The proposed work will provide both conceptual and experimental frameworks towards our long-term goal of exploring the channels and barriers of transgenerational epigenetic inheritance.

PI_NAMEs: GU, GUOPING  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Aging;Animals;Biochemical;Biochemistry;Caenorhabditis elegans;Cell Physiology;Cells;Chromatin;chromatin modification;Chromatin Structure;Development;Disease;DNA;Double-Stranded RNA;Environment;Environmental Impact;Enzymatic Biochemistry;Enzymes;Epigenetic Process;epigenetic silencing;feeding;Funding;gene repression;Generations;Genes;Genetic;Genetic Materials;Genome;Genome Stability;genomic tools;Genomics;Germ Lines;Goals;Guide RNA;Health;Heat Stress;Heritability;Heterochromatin;Histone Code;histone methyltransferase;histone modification;Histones;Human;insight;Location;Mammals;Mediating;model organism;Molecular;novel;Nuclear;Pathway interactions;Plants;Play;Post-Translational Protein Processing;Proteins;Regulation;reproductive;Research;RNA;RNA Interference;Small Interfering RNA;Small RNA;System;theories;transgenerational epigenetic inheritance;Work

PROJECT_TITLE: RNA-mediated Chromatin Regulation and Transgenerational Epigenetic Inheritance in C. elegans


ORG_CITY: BIRMINGHAM

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The research plan is relevant to public health because it explores a novel series of endogenous products derived from normal tryptophan metabolism that have the potential to modulate cellular and systemic responses. Understanding the formation and regulation of these products will not only provide new insights into the biological actions of an essential nutrient, but also has the potential to open new avenues for the development of therapies aimed at improving conditions in which tryptophan metabolism is dysregulated. Thus, this proposal is significant to the NIH mission in that it seeks to apply fundamental knowledge to enhance health, lengthen life, and reduce illness and disability.

PI_NAMEs: VITTURI, DARIO A (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Affect;Aging;Biochemical;Bioenergetics;Biological;Biology;Brain;Cardiovascular Diseases;Catabolism;Cell Physiology;cell type;Chemistry;Clinical;Cysteine;Data;Deamination;Development;dietary;disability;Enzymes;Foundations;Glutathione;Health;Heart;Hepatocyte;Human;Immunity;improved;in vivo;Individual;insight;Intake;interest;Isotope Labeling;Kidney;Kinetics;Knowledge;Kynurenine;Label;Life;Liver;Malignant Neoplasms;Mass Spectrum Analysis;Mediator;Metabolic Biotransformation;Metabolism;microbiome;Mission;Mus;N'-formylkynurenine;novel;Nutrient;organ injury;outcome prediction;Oxidation-Reduction;Paracrine Communication;Pathway interactions;Pregnancy;Process;protein function;Public Health;Publishing;Reaction;Regulation;Research;Resolution;response;Role;Secondary to;Series;Signal Transduction;Site;Solid;Source;therapy development;Tissues;transcription factor;Transcription Regulatory Protein;transcriptomics;Transplantation;Tryptophan;Tryptophan Metabolism Pathway;tumor microenvironment;United States National Institutes of Health

PROJECT_TITLE: Formation, metabolism and cell signaling actions of tryptophan catabolism-derived electrophiles

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


NIH_SPENDING_CATS: Infectious Diseases

PHR: Project Narrative This work will contribute to a fundamental understanding of the mechanisms of integral membrane protein quality control systems, including endoplasmic reticulum-associated degradation (ERAD). ERAD is a central system for cellular stress response and adaptation. A mechanistic understanding of the system and the processes it regulates will establish aspects of this system as viable therapeutic targets in medically relevant pathways of protein misfolding, protein misregulation, and pathogen hijacking.

PI_NAMEs: BALDRIDGE, RYAN DOUGLAS (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Address;Antigen-Antibody Complex;Biochemical;Biochemistry;Biological Assay;Cells;Cellular biology;Cellular Stress;Cytosol;Data;design;Dislocations;Endoplasmic Reticulum;endoplasmic reticulum stress;Genetic;Goals;in vitro Assay;in vivo;innovation;Integral Membrane Protein;Mechanics;Medical;Membrane;Membrane Proteins;multicatalytic endopeptidase complex;Organelles;pathogen;pathogenic bacteria;pathogenic virus;Pathway interactions;Physiological;Process;protein misfolding;Proteins;Quality Control;System;therapeutic target;Work

PROJECT_TITLE: Protein quality control at eukaryotic membranes


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: PROJECT NARRATIVE We build upon our previous successes developing and using genetically encoded single-fluorescent protein biosensors to measure intracellular concentrations of signaling metabolites in different parts of a cell. This will provide a deeper understanding of how cell metabolism can change cellular behavior. Consequently, we can use this information to direct future efforts for new disease interventions.

PI_NAMEs: CAMBRONNE, XIAOLU ANG (contact)

PROJECT_TITLE: Localized Real-time Sensors for Metabolic Signaling


NIH_SPENDING_CATS: Clinical Research;Hematology

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Narrative: Human long-lived plasma cells (LLPC) are responsible for life-long protection from vaccines. Our studies will address fundamental processes underlying the development, maturation and survival of human plasma cells with the final goal of determining the impact of different factors and tissue niches in the generation and durability of LLPC.

PI_NAMEs: LEE, FRANCES EUN-HYUNG (contact)

PROJECT_TERMS: Acute;Adult;Affect;Antibodies;Antigens;autocrine;Autoimmune Diseases;Autoimmune hemolytic anemia;Binding;Binding Sites;Blood;Blood Circulation;Bone Marrow;Cell Differentiation process;cell growth;Cell Maturation;Cell Physiology;Cell secretion;Cell Survival;Cellular Morphology;Cleavage Under Targets and Release Using Nuclease;Collaborations;Color;Complex;cytokine;Data;Development;Down-Regulation;Epigenetic Process;epigenome;Flow Cytometry;Foundations;Generations;Genetic Transcription;Genus Mentha;Goals;Grant;Heterogeneity;Human;human model;Idiopathic Thrombocytopenic Purpura;IL6ST gene;Immunoglobulin-Secreting Cells;Immunoglobulins;In Vitro;in vivo;Individual;Infection;Inflammatory;inhibiting antibody;Inhibition of Apoptosis;inhibitor;Interferon Type II;Interleukin 6 Receptor;Interleukin-10;Interleukin-12;interleukin-21;interleukin-21 receptor;Interleukin-6;Ligands;lymph nodes;Macrophage;malaria infection;Measures;Mediating;mesenchymal stromal cell;microbial;midkine;migration;Modeling;Molecular;mouse model;Mus;nonhuman primate;novel;Organ;Parasites;Pathogenicity;Pathway Analysis;Pattern;Phase;Phenotype;Phosphorylation;Plasma Cells;Plasmodium;Play;Population;prevent;Process;programs;Reaction;receptor;Recovery;Regulatory Pathway;residence;response;Role;Serum;Signal Transduction;single-cell RNA sequencing;Specificity;Spleen;STAT3 gene;Stromal Cells;Structure of germinal center of lymph node;T-Lymphocyte;Testing;Tissues;transcriptome;Transplantation;Vaccines

PROJECT_TITLE: Molecular Mechanisms of Human Long-lived Plasma Cell Generation in the Bone Marrow and Spleen


ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE This proposed work will explore and unveil mechanisms of how the HPV minor capsid protein is able to peek through and stably insert into endosomal membranes. Deeper knowledge into processes like these will advance our fundamental understanding of protein-membrane interactions. The lessons learned by studying HPV and understanding the endosomal microenvironmental requirements will help our understanding of similar membrane translocation processes, common to other viruses and bacterial toxins and may very well reveal pathways that are used by cellular proteins as well.

PI_NAMEs: CAMPOS, SAMUEL K (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Bacterial Toxins;C-terminal;Capsid Proteins;Cells;Cellular biology;Elements;endosome membrane;Endosomes;Family;gamma secretase;Golgi Apparatus;Human Papillomavirus;Infection;insight;Ions;Knowledge;L2 viral capsid protein;lens;Membrane;Membrane Proteins;Minor;Organism;Pathway interactions;Penetration;Peptides;Process;protein transport;Proteins;retrograde transport;Role;Signal Transduction;sorting nexins;trafficking;Transmembrane Domain;Viral;virology;Virus;Work

PROJECT_TITLE: Membrane Spanning and Subcellular Trafficking Mechanisms of a Viral Capsid Protein- Lessons from a Master Cell Biologist


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: BURLINGTON

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: PROJECT NARRATIVE The four serotypes of dengue virus cause 100 million cases of disease annually in humans. Durable tetravalent dengue vaccines are necessary to control disease but must safely protect against all four serotypes. We propose to use human specimens available from innovative dengue vaccine/viral challenge models and apply novel cellular and molecular approaches to define how vaccine-induced development of dengue-specific immunity safely and durably protects against infection and disease.

PI_NAMEs: DIEHL, SEAN A. (contact);DURBIN, ANNA PALMER;KIRKPATRICK, BETH DIANE

PROJECT_TERMS: adaptive immunity;Address;Adolescent;Adult;Age;Antibodies;Antibody-Dependent Enhancement;Antibody-Producing Cells;Antigens;Area;Attenuated;B-Lymphocytes;Bangladesh;Bangladeshi;Biological Assay;CD8-Positive T-Lymphocytes;Child;Clinical;Clinical Research;Clinical Trials;cohort;Complement;cross reactivity;Cytolysis;cytotoxic;Cytotoxic T-Lymphocytes;Data;Dengue;Dengue Vaccine;Dengue Virus;design;Development;dimer;Disease;disorder control;disorder risk;Epitopes;Exposure to;Flaviviridae;follow-up;Funding;Growth;Hospitalization;Human;Immune;Immune response;Immunity;immunogenicity;Immunologics;Individual;Infection;innovation;insight;Knowledge;Letters;Lytic;Mediating;Modeling;Molecular;National Institute of Allergy and Infectious Disease;neutralizing antibody;novel;Persons;Play;Population;prevent;protective efficacy;Research Personnel;response;Risk;Role;Safety;Sampling;Scientist;Serotyping;Specimen;T cell response;T-Lymphocyte;Travel;United States;United States National Institutes of Health;Vaccinated;Vaccination;vaccine candidate;vaccine platform;Vaccinee;Vaccines;vector mosquito;Viral;Viral Nonstructural Proteins;Viral Physiology;Virus;Work

PROJECT_TITLE: Mechanisms of Protection and Durability for a Live Attenuated Tetravalent Dengue Vaccine


NIH_SPENDING_CATS: Genetics

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: PROJECT NARRATIVE The highly conserved bone morphogenetic protein (BMP) signaling pathway plays critical roles in a variety of developmental and homeostatic processes. Defects in this pathway can result in various disorders, including cancer, as well as musculoskeletal and cardiovascular diseases. Identifying regulators and targets of BMP signaling and determining how they function in vivo will not only yield critical insight into our general understanding of development and diseases, but may also help identify potential therapeutic targets for the diseases caused by mutations in the BMP pathway.

PI_NAMEs: LIU, JUN  (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Animals;Bone Morphogenetic Proteins;Caenorhabditis elegans;Cardiovascular Diseases;Cell surface;Cells;Complex;Defect;Development;Disease;extracellular;Genetic Screening;Genetic study;Goals;Hereditary Disease;Human;Image;in vivo;insight;Malignant Neoplasms;Membrane;metabolomics;Modeling;Molecular;Molecular Genetics;Musculoskeletal Diseases;Mutation;Pathway interactions;Play;Process;Productivity;protein phosphatase inhibitor-2;Protein Secretion;Proteins;Proteomics;Regulation;Research;Resolution;Role;Signal Pathway;Signal Transduction;Signaling Protein;skeletal disorder;therapeutic target;Time;transcription factor

PROJECT_TITLE: Molecular mechanisms regulating and interpreting BMP signaling


ORG_DEPT: BIOLOGY

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: Project Narrative Billions of cells die every day in the human body, and these cells must be removed to prevent inappropriate immune responses. Our research aims to understand how cell death and corpse clearance are controlled and coordinated, and how defects in these processes affect organismal health. A complete understanding of the diverse mechanisms controlling cell death and cell clearance may reveal new therapeutic targets for diseases such as neurodegenerative disorders and cancer.

PI_NAMEs: MCCALL, KIMBERLY A (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Address;Affect;Animals;Apoptosis;Biological;Brain;Cell Death;cell transformation;cell type;Cells;Defect;Development;Disease;Drosophila genus;egg;Epithelial Cells;Epithelium;Excision;fly;Future;Genetic;Genomics;Germ Lines;Health;Homeostasis;Human;Human body;human disease;immune activation;Immune response;Immune signaling;insight;Link;lysosomal proteins;Macrophage;Maintenance;Malignant Neoplasms;Mammals;model organism;Modeling;Nerve Degeneration;Neurodegenerative Disorders;new therapeutic target;Nurses;Organism;Ovary;Pathway interactions;Phagocytes;Phagocytosis;Physiological;Predisposition;prevent;Process;programs;Research;response;Starvation;Tissues;tool;Work

PROJECT_TITLE: The coordination of cell death and corpse clearance in Drosophila

STUDY_SECTION: MRAC

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


ORG_CITY: HADLEY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

PHR: PHS statement / Narrative. The highly conserved ClpXP and Lon proteases are critical for bacterial stress responses. Because loss of these proteases in pathogenic bacteria results in loss of virulence, identifying how these proteases are regulated and what pathways they govern will be of immense value for the pursuit of new therapies.

PI_NAMEs: CHIEN, PETER  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Allosteric Regulation;Bacteria;Biochemistry;biological adaptation to stress;Caulobacter;Cell Cycle;Dedications;Development;DNA-Binding Proteins;endopeptidase La;Genetic;Growth;Hydrophobicity;insight;Ligands;Modeling;Molecular;Molecular Conformation;novel therapeutics;pathogenic bacteria;Pathway interactions;Peptide Hydrolases;protein folding;Protein Region;Proteins;Proteolysis;Proteomics;Quality Control;recruit;Regulation;Replication-Associated Process;Role;Specificity;System;transposon sequencing;Virulence;Work

PROJECT_TITLE: Regulated Proteolysis in Bacteria Development and Stress Response

STUDY_SECTION: MRAA

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


ADMINISTERING_IC: CA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: OVERALL PROJECT NARRATIVE Yale Cancer Center (YCC) is committed to eliminating the burden of cancer through transformative research, with attention to the needs of all people facing this disease. Our goal is to understand and prevent cancer, detect cancer early, and manage cancer more effectively, while maximizing access to care, addressing the needs of the community, ensuring equity and diversity in our workplace, and training future cancer researchers, clinicians, and leaders.

PI_NAMEs: WINER, ERIC P (contact)

PROGRAM_OFFICER_NAME: HE, MIN

PROJECT_TERMS: Academia;Address;AIDS related cancer;anti-cancer research;Area;Attention;Award;Back;Basic Cancer Research;Basic Science;Biological Markers;Cancer Burden;cancer care;Cancer Center Support Grant;cancer health disparity;cancer prevention;cancer therapy;career development;Caring;Catchment Area;Clinic;Clinical;clinical care;Clinical Sciences;Clinical Trials;Collaborations;combat;Communicable Diseases;Communities;community involvement;Connecticut;design;Diagnosis;Direct Costs;Disease;Disparity;Disparity in diagnosis;disparity reduction;Diverse Workforce;diversity and equity;Dreams;Ensure;Equity;Fostering;Funding;Future;Goals;Grant;Health Services Accessibility;Heart;Improve Access;improved;Individual;Industry;innovation;Institution;Investments;Journals;Knowledge;Laboratories;Leadership;Link;Malignant Neoplasms;member;Mentors;NCI Center for Cancer Research;next generation;novel;novel therapeutic intervention;Outcome;Output;Patient Selection;Patients;Peer Review;Persons;Physicians;Population;Population Sciences;prevent;programs;Publications;Recording of previous events;recruit;Research;Research Personnel;Resource Sharing;Resources;Role;Scientist;Screening for cancer;Services;social health determinants;Source;Strategic Planning;synergism;Technology;therapy resistant;Training;Training and Education;Translating;Translational Research;Universities;Vision;Work;Workplace;Yale Cancer Center

PROJECT_TITLE: Integrated Infectious Diseases and Cancer Care to Address SDOH for Patients with HIV-associated Cancer (Social Determinants of Health and Quality of Cancer Care in HIV-associated Cancers)


ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: Narrative Dysregulation of cell signaling is the cause for many diseases, yet the underlying mechanistic details are incompletely understood. This project will apply advanced microscopy and cell biology approaches to the study of signaling pathways that are involved in driving cancer and allergy/asthma. Our goal is to translate this new and fundamental knowledge about signaling mechanisms into therapeutic understanding.

PI_NAMEs: LIDKE, DIANE  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Antigens;Asthma;Automobile Driving;Behavior;Biochemical;Biological Process;Biology;Biophysics;Cell Physiology;Cells;Cellular biology;Chemicals;Collaborations;Complex;Cues;Disease;Environment;Epidermal Growth Factor Receptor;Event;Geometry;Goals;Hypersensitivity;Image;Imaging Techniques;innovation;Integrins;Knowledge;Ligands;Malignant Neoplasms;mast cell;mechanical signal;Membrane;Microscopy;Molecular;novel therapeutics;Outcome;Pathogenesis;Post-Translational Protein Processing;Process;protein protein interaction;Proteins;receptor;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Regulation;Research;response;Shapes;Signal Pathway;Signal Transduction;Specificity;System;Techniques;Therapeutic;Translating;tumorigenesis

PROJECT_TITLE: Imaging the Early Events in Membrane Receptor Signaling


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Hematology;Microbiome;Neurosciences;Physical Injury - Accidents and Adverse Effects;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: GAINESVILLE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: NARRATIVE Traumatic injury followed by critical illness provokes pathophysiologic changes in the bone marrow and the gut that contribute to persistent anemia and changes in the microbiome which significantly impact long-term recovery. This project will define the interactions between the stress, chronic inflammation, bone marrow dysfunction, and an altered microbiome which will provide a strong foundation for future clinical interventions to help improve outcomes following severe trauma.

PI_NAMEs: MOHR, ALICIA M (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Age;Age Years;Anemia;Area;beta diversity;biological adaptation to stress;Blood Transfusion;Bone Marrow;Brain;Catecholamines;Cause of Death;Chronic;Chronic stress;Clinical;cohort;Critical Illness;Erythroid;Erythroid Progenitor Cells;erythropoiesis inhibitor;Erythropoietin;Foundations;Functional disorder;Future;Goals;hematopoietic stem cell fate;Hematopoietic stem cells;Human;Impairment;improved;improved outcome;Inflammation;Innate Immune Response;Intervention;Iron;Laboratories;Life;Link;long term recovery;microbial composition;microbiome;microbiome alteration;microbiota;Morbidity - disease rate;novel;Outcome;Patients;Persons;pre-clinical;Principal Investigator;Productivity;Quality of life;Regulation;Research;response;Risk;Rodent;Rodent Model;Role;severe injury;sex;stem cell fate;stem cell function;stem cell homeostasis;Stress;stress reduction;survivorship;systemic inflammatory response;transcriptomics;Trauma;Traumatic injury

PROJECT_TITLE: The Role of Brain-Bone Marrow-Gut Interaction following Major Trauma


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Eczema / Atopic Dermatitis;Patient Safety;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: NEW YORK

ORG_DEPT: DERMATOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Alopecia areata (AA) is a complex T-cell-driven disease, lacking treatments in children with moderate-to-severe AA. We have established a Type 2 immune polarization in AA, particularly in atopic patients, and also the ability to regrow hair with specific Th2-targeting with dupilumab in adult patients with atopy and/or high IgE. In this placebo-controlled study we test the safety and efficacy of dupilumab in children (6-17yo) with extensive (≥50% scalp loss), coupled with molecular profiling of inflammatory, regulatory, and hair-associated keratins, with the potential to change the treatment paradigm for children with AA, and also expand its mechanistic understanding.

PI_NAMEs: GUTTMAN, EMMA  (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: 17 year old;Adolescent;Adult;Adverse event;Affect;Aftercare;Alopecia;Alopecia Areata;antagonist;Atopic Dermatitis;atopy;Biological Markers;Biopsy;Blocking Antibodies;Blood;Child;Childhood;Chronic;Clinical;clinical effect;clinical efficacy;Clinical Trials;comorbidity;Complex;Coupled;Coupling;Cyclosporine;cytokine;Data;Development;Disease;Distress;Double-Blind Method;Economic Burden;exhaustion;Flow Cytometry;follow-up;Gene Expression Profiling;Growth;Hair;IgE;Immune;impression;indexing;Inflammation;Inflammatory;inflammatory modulation;inhibiting antibody;Interleukin-13;Interleukin-4;Janus kinase;Keratin;kinase inhibitor;Laboratories;lifetime risk;Measures;Mediating;Molecular;Molecular Profiling;Monitor;Monoclonal Antibodies;Nature;open label;Oral;Pathogenesis;Pathway interactions;Patients;pediatric patients;Phenotype;Physical Examination;placebo controlled study;Placebos;Population;primary endpoint;Proteins;psychosocial;PUVA Photochemotherapy;Quality of life;Quality of Life Assessment;Randomized;Randomized, Controlled Trials;Recurrence;Regulatory Pathway;Reporting;response;Role;Safety;safety assessment;safety testing;Scalp structure;Serum;Severities;side effect;Signal Transduction;Skin;skin disorder;Societies;Solid;stem cell biomarkers;Steroids;subcutaneous;Symptoms;systemic inflammatory response;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Tissues;tool;transcriptome sequencing;Withholding Treatment

PROJECT_TITLE: Dupilumab in the Treatment of Pediatric Alopecia Areata

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 AM-I (S1)]


PHR: Project Narrative  We have limited structural information on membrane proteins and channels, but they play an important part in numerous biomedical diseases such as heart disease and cancer. New biophysical tools are urgently needed to study membrane proteins. The research discussed in this MIRA R35 application will develop new biophysical methods for studying the structural and dynamic properties of integral membrane proteins and channels. We will also apply these methods to probe the structure of several different biological systems.  We will focus on investigating the structural and dynamic properties of integral membrane proteins in the KCNE family which is responsible for the modulation of voltage gated potassium (Kv) channels including KCNQ1 (Q1). This channel is expressed throughout the body to regulate physiological functions and mutations in this channel are linked to several diseases such as Long QT syndrome and other heart diseases. Increased understanding of the molecular underpinnings of KCNE modulation of potassium channels, specifically Q1, would help expand our understanding of the etiology of these diseases. We will study three members of the KCNE family: KCNE1(E1), KCNE3(E3), and KCNE4(E4). When E1 forms a complex with Q1, it causes the activation kinetics of the channel to slow, giving rise to the slow-delayed rectifier potassium channel, IKs, which is crucial to the repolarization of cardiac action potential. E3 forms a complex with Kv channels that are voltage-independent under physiological ranges. Q1/E3 channels are important for cardiac action potentials and transport of nutrients across epithelial cells. A major gap in our understanding of E3 is due to limited structural information. E4 has been shown to inhibit current in Kv channels, including Q1. Previously, the role of E4’s tetraleucine motif has been tied to its inhibitory effects and interaction with Kv channels. It is currently not understood how the tetraleucine motif drives protein-protein interactions and how this leads to changes in the structure of E4 Presently, E3 and E4 are being studied in the Lorigan lab to provide knowledge regarding structure, topology, and dynamics which can lead to better molecular level understanding as previously done with E1.  Over the next five years, we will: (1) Develop new biophysical techniques to dramatically improve structural studies of membrane proteins, (2) Probe the structural and dynamic properties of E3, and E4, (3) Elucidate the binding mechanism of E1 and Q1 to help us better understand the mechanism of Q1 regulation, and (4) Apply the membrane protein techniques that we develop to investigate the structure of several biologically important integral membrane proteins (S2E Coronavirus Envelope Protein, Canonical Holin, TRPV1, and Grp94) using pulsed EPR spectroscopy. The TRPV1, and GRP94 projects will be done via collaboration. Each lab will send us samples for pulsed EPR measurements. Transformative biophysical techniques will be developed to study the structural and dynamic properties of membrane proteins. These state-of-the-art pulsed EPR spectroscopic techniques will move the field forward by dramatically increasing sensitivity and distance measurements of membrane protein systems such as E3 and E4. Also, a new polymer-based membrane mimetic system will be developed that will enable researchers to more easily conduct structural and functional measurements of membrane proteins in a lipid bilayer. The size of the SMALPs can be fine-tuned by the polymer to match the size of the membrane protein complex. The state-of-the-art pulse EPR techniques, unique spin labels, and our powerful SMALPs membrane systems will dramatically improve our ability to study the structure and dynamics of a wide variety of different membrane protein complexes of various sizes.

PI_NAMEs: LORIGAN, GARY A (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: Action Potentials;Binding;Biological;biological systems;biophysical techniques;biophysical tools;Biophysics;Cardiac;Cell membrane;Collaborations;Complex;Coronavirus;Coupled;Data;delayed rectifier potassium channel;Detergents;Disease;Electron Spin Resonance Spectroscopy;env Gene Products;Epithelial Cells;Etiology;experimental study;Family;Goals;GRP94;Heart Diseases;improved;instrumentation;Integral Membrane Protein;interest;Ion Channel;Kinetics;Knowledge;Letters;Link;Lipid Bilayers;Long QT Syndrome;Malignant Neoplasms;Measurement;Measures;member;Membrane;Membrane Proteins;Methods;Micelles;mimetics;Molecular;Mutation;Nutrient;Physiologic pulse;Physiological;Play;Polymers;Potassium;Potassium Channel;Preparation;Property;protein complex;protein protein interaction;Proteins;Regulation;Research;Research Personnel;Role;Sampling;spectroscopic survey;Spin Labels;Structure;System;Techniques;TRPV1 gene;voltage;Work

PROJECT_TITLE: EPR Spectroscopic Studies of Membrane Proteins


PHR: Project Narrative The proposed research will develop new computational and experimental tools to study 3D chromatin struc- ture and apply them to understand the mechanisms and phenotypic impacts of a newly discovered class of 3D chromatin structures, phase separation-driven chromatin loops.

PI_NAMEs: PHANSTIEL, DOUGLAS H. (contact)

PROJECT_TERMS: 3-Dimensional;Chromatin Loop;Chromatin Structure;Communities;computerized tools;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Human Development;Maps;Phase;Phenotype;Play;promoter;Research;response;Role;Stimulus;tool;Visualization;Work

PROJECT_TITLE: Mechanisms and impacts of chromatin looping


NIH_SPENDING_CATS: Nutrition

ORG_CITY: College Station

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

PHR: PROJECT NARRATIVE Copper is an essential trace metal required by mitochondria to produce energy from the food we eat. Genetic defects in copper transport to mitochondria result in debilitating and often fatal pediatric disorders for which no approved treatment is available. In the proposed research, we seek to build on our recent discoveries in copper trafficking to mitochondrial energy-generating machinery and leverage this information to discover copper- transporting drugs with therapeutic potential.

PI_NAMEs: GOHIL, VISHAL MAHENDRASINGH (contact)

PROJECT_TERMS: Adjuvant;Aerobic;Biological Models;Biology;Cell Respiration;Cells;Childhood;cofactor;Copper;cytochrome c oxidase;Disease;disease-causing mutation;Drug Transport;Eating;Enzymes;Food Energy;Generations;Genomics;Goals;Growth and Development function;hypocupremia;improved;infancy;interdisciplinary approach;Knowledge;Menkes Kinky Hair Syndrome;Metabolic Pathway;Micronutrients;Mitochondria;Mitochondrial Diseases;Mitochondrial Matrix;mitochondrial metabolism;model organism;Molecular;mouse model;Mutation;novel;Organism;Pathway interactions;Play;programs;Property;Proteomics;Research;Role;Safety;small molecule;success;Therapeutic;Trace metal;trafficking;Translating;Work;Yeast Model System;Yeasts;Zebrafish

PROJECT_TITLE: Mitochondrial Copper Biology


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Genetics;Human Genome;Immunization;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: KINGSTON

ORG_NAME: UNIVERSITY OF RHODE ISLAND

ORG_STATE: RI

PHR: Project Narrative  This project will apply comprehensive flow cytometry and single-cell RNA sequencing to identify functional, transcriptomic, and epigenomic profiles in individual dengue virus (DENV)-specific T and B lymphocytes present early after immunization that are predictive of the durability of DENV-specific serological immunity over a >8-year follow-up period.

PI_NAMEs: ROTHMAN, ALAN L (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: 2019-nCoV;Address;Antibodies;Antibody Response;Antigens;ATAC-seq;Attenuated Vaccines;B-Lymphocytes;Binding;Blood specimen;Cells;Chromatin;Clonality;cohort;Data;Dengue;Dengue Infection;Dengue Vaccine;Dengue Virus;Disease;Elements;Epigenetic Process;epigenomics;Flow Cytometry;follow-up;Frequencies;Gene Expression;Generations;Genetic Transcription;global health;Goals;Immune;Immune response;Immunity;Immunization;Immunologics;improved;Individual;Infectious Agent;influenza virus vaccine;innovation;Knowledge;Lead;Licensing;Licensure;Longitudinal Studies;neutralizing antibody;Participant;pathogen;Peripheral Blood Mononuclear Cell;Pertussis;Phase;Phase III Clinical Trials;phase III trial;Population;response;Safety;Secondary Immunization;Serology;single-cell RNA sequencing;Smallpox;Sorting;Specificity;T memory cell;T-Lymphocyte;Testing;Time;transcriptomics;Vaccination;vaccine development;vaccine efficacy;vaccine immunogenicity;vaccine trial;Vaccines;Yellow Fever;Yellow Fever Vaccine

PROJECT_TITLE: Long-term durability of DENV-specific immunity after vaccination in a dengue-endemic population


NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_CITY: GALVESTON

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

PHR: Project Narrative This research project will deepen our understanding of how proteins scan and recognize DNA. New knowledge from this project can help improve therapeutics for human diseases caused by problems with DNA-binding proteins.

PI_NAMEs: IWAHARA, JUNJI  (contact)

PROJECT_TERMS: Behavior;Binding;biophysical techniques;Cells;Communication;Complex;Diffusion;Disease;Dissociation;DNA;DNA Binding Domain;DNA-Binding Proteins;DNA-Protein Interaction;Electrostatics;Free Energy;Functional disorder;Gene Expression;genome integrity;human disease;improved;Knowledge;Life;Methodology;Methods;Microscopic;Molecular;NMR Spectroscopy;Nuclear Magnetic Resonance;Post-Translational Protein Processing;Process;Protein Dynamics;protein structure;Proteins;Research;Research Project Grants;Scanning;stopped-flow fluorescence;structural biology;Structure;Therapeutic;three dimensional structure

PROJECT_TITLE: Dynamics of DNA scanning and recognition by proteins


ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Proteins catalyze most of the reactions on which life depends, so it is of no surprise that there are many links between the dysregulation of protein synthesis and disease progression. An understanding of the mechanism and regulation of human protein synthesis will help us better understand the progression of many diseases and provide novel drug targets.

PI_NAMEs: FRASER, CHRISTOPHER S (contact)

PROJECT_TERMS: Biological Assay;Cells;crosslink;Disease;Disease Progression;Event;Fluorescence;genome-wide analysis;Hour;Human;Immunoprecipitation;Initiator Codon;innovation;Kinetics;Knowledge;Life;Link;Messenger RNA;model building;Modeling;Monitor;new therapeutic target;Pathway interactions;Peptide Initiation Factors;Physiological;Post-Translational Protein Processing;programs;Protein Biosynthesis;Proteins;Reaction;reconstitution;recruit;Regulation;response;ribosome profiling;Ribosomes;single molecule;Site;Stimulus;Sucrose;System;Testing;Thermodynamics;Time;Translating;translation assay;Translations

PROJECT_TITLE: The mechanisms of mRNA recruitment to the human ribosome


ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: The ASCENT T32 training program, under the auspices of the New Jersey Alliance for Clinical and Translational Science, is designed to provide predoctoral students from Rutgers University, Princeton University, and the New Jersey Institute of Technology a 2-year opportunity to increase their knowledge, skills, and abilities in translational science to prepare them for their careers in translational biomedical science.

PI_NAMEs: MITROFANOVA, ANTONINA ;NOTTERMAN, DANIEL A.;SCOTTO, KATHLEEN W. (contact)

PROGRAM_OFFICER_NAME: DIBELLO, ANTHONY THOMAS

PROJECT_TERMS: Health Sciences;New Jersey;pre-doctoral;Translational Research

PROJECT_TITLE: NJ ACTS: A Platform for Translational Science in New Jersey: CTSA Predoctoral T32 at Rutgers, Biomedical Health Sciences


ORG_DEPT: NEUROSCIENCES

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: DNA methylation, chromatin, transcription initiation and alternative splicing form a tightly linked triangle and single-cell genomics has revolutionized modern-day biology. However, to-date we are lacking a precise understanding of the relationships between the above modalities in the cell types that form complex tissue. Here, we devise new single-cell technology to measure multiple modalities to infer the relationships between them in health and disease.

PI_NAMEs: TILGNER, HAGEN ULRICH (contact)

PROJECT_TERMS: Adult;Alternative Splicing;Bar Codes;Bioinformatics;Biological Sciences;Biology;Brain region;Cell Nucleus;cell type;Cells;Chromatin;Complementary DNA;Complex;Computer software;Data;Detection;Development;Disease;DNA Methylation;Error Sources;Event;experimental study;Freezing;frontier;Frontotemporal Dementia;Funding;Future;Gene Expression;Genetic;Genome;Health;human tissue;Individual;Knowledge;Link;Measurable;Measurement;Measures;Methods;MicroRNAs;Modality;Modernization;multiple omics;Mus;Names;nanopore;National Institute of General Medical Sciences;Nature;Neuroglia;Neurons;novel;Nucleotides;Outcome;Pattern;Protein Isoforms;protein protein interaction;Research;Resolution;RNA;RNA Splicing;single cell genomics;single cell technology;single molecule;Slide;Spliced Genes;Spliceosomes;Technology;Testing;Time;timeline;Tissues;Transcription Initiation;Transcription Initiation Site;transcriptome sequencing;Visualization software

PROJECT_TITLE: Multiome measurements connecting transcription start sites at single-nucleotide resolution, DNA methylation and open chromatin status to splicing outcome across single cells in health and disease


ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

PHR: Eukaryotic genomes are partitioned into distinct functional domains by chromatin modifications. This project will investigate the Polycomb Group chromatin modification system and will generate information about the control and function of Polycomb Repressive Complex 2, a conserved histone methyltransferase that is mutated or dysfunctional in human Weaver syndrome and multiple cancer types. This work will ultimately facilitate development of new tools to prevent, diagnose and treat cancer and other human diseases.

PI_NAMEs: LEWIS, ZACHARY  (contact)

PROJECT_TERMS: Address;Animals;cancer genetics;cancer type;cellular development;Chromatin;chromatin modification;chromatin remodeling;Complex;Development;Diagnosis;DNA biosynthesis;Enzymes;Epigenetic Process;Eukaryota;Fission Yeast;Fungi Model;fungus;Future;Gene Expression Regulation;Genes;Genetic;Genetic Diseases;Genetic Screening;Genome;Genomic approach;Goals;Grant;Health;histone methyltransferase;Human;human disease;improved;insight;Investigation;ISWI;Knowledge;link protein;Maintenance;Malignant Neoplasms;Molecular;Multienzyme Complexes;Mutate;Mutation;Neurospora crassa;Nucleosomes;Other Genetics;Plants;Play;Polycomb;prevent;Proteins;Proteomics;Regulation;Repression;Saccharomyces cerevisiae;Slide;stem cells;System;tool;Weaver Syndrome;Work;X Inactivation;Yeast Model System

PROJECT_TITLE: Control and function of repressive chromatin domains


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: CAMBRIDGE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: The selective transformation of small molecules by naturally occurring proteins known as enzymes produces important products that have far-ranging roles in biological function from signaling pathways to fighting disease. Medicinal chemistry would benefit from having the same tools to selectively transform small molecules for the creation of therapeutic drugs. This project seeks to use computational modeling techniques to increase the fundamental mechanistic understanding of how enzymes enable selective transformations and to improve the rational approaches that can be used to mimic natural enzymes in medicinal chemistry.

PI_NAMEs: KULIK, HEATHER J. (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Revealing Nature's Blueprints for Single-Site Catalysis of C-H Activation with First-principles Modeling and Machine Learning


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Complementary and Integrative Health;Emerging Infectious Diseases;Foodborne Illness;Genetics;Infectious Diseases;Rare Diseases

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative (relevance to public health) Understanding the physiological responses of human pathogens such as Vibrio cholera and Pseudomonas aeruginosa to environmental and genetic perturbations and connecting these responses to underlying gene regulatory controls will potentially open up treatment strategies at a systems level. Elucidating adaptive strategies to the inhibitory effects of SCFA on bacterial growth will provide valuable input to the rationale design of probiotics, to endow them with unique fitness advantages in the gut environment so that they can outcompete the undesirable pathogens.

PI_NAMEs: HWA, TERENCE  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TITLE: Quantitative Systemic Studies of Bacterial Physiology


NIH_SPENDING_CATS: Brain Disorders;Breast Cancer;Cancer;Cerebrovascular;Hematology;Neurosciences;Rare Diseases;Stroke;Women's Health Research

ORG_CITY: CHICAGO

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

ORG_STATE: IL

PHR: Project Narrative Voltage-gated proton channel are proteins that help white blood cells kill bacteria, sperm fertilize eggs, and heart muscle remain healthy. But their abnormal function can promote leukemia, breast cancer metastasis, autoimmune diseases, and brain damage in stroke. By discovering how proton channels work, and which of their parts are important, this project will enable designing drugs to control their activity.

PI_NAMEs: DECOURSEY, THOMAS E (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Autoimmune Diseases;B-Lymphocytes;Bacteria;Basophils;Brain Injuries;breast cancer metastasis;cell killing;Cells;Cholesterol;Chronic Lymphocytic Leukemia;Disease;Drug Design;Family;Functional disorder;Future;Genes;Health;Histamine Release;Human;human tissue;Ion Channel Gating;Ischemic Stroke;Knowledge;Learning;leukemia;Leukocytes;Liquid substance;Malignant Neoplasms;Membrane Lipids;Membrane Microdomains;Membrane Potentials;Mutation;Myocardium;Physiological;Play;Productivity;Proteins;Protons;Regulation;Role;Signal Transduction;sperm cell;Sperm Maturation;Sperm Motility;Stroke;Structure;Structure-Activity Relationship;Tissues;voltage;Work;zygote

PROJECT_TITLE: Control Mechanisms of Human Voltage Gated Proton Channels, hHv1


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Even though the ribosome has evolved to make all the cellular proteins, synthesis of specific polypeptides can be problematic. Cells produce special accessory factors to assist the ribosome in synthesizing the difficult- to-make proteins, but how these factors work and when their help is needed is unknown. Finding the functions of the molecular aids of the ribosome will advance our understanding of the fundamental mechanisms of protein synthesis and provide foundation for developing new medicines and treating diseases related to faulty protein expression.

PI_NAMEs: MANKIN, ALEXANDER S (contact)

PROJECT_TERMS: Antibiotics;Bacterial Genome;Biological Models;Cells;crosslink;Data;design;Development;Disease;Educational process of instructing;experimental study;Foundations;Genes;genetic information;genome-wide;Genomics;Goals;Growth;In Vitro;in vivo;innovation;interest;Knowledge;Laboratories;learning ability;Maps;Medicine;Messenger RNA;Methodology;Modeling;Molecular;Molecular Mechanisms of Action;mutant;Nature;outreach;Physiological;Play;Polymers;polypeptide;Property;Protein Biosynthesis;protein expression;Proteins;recruit;Reporter;Research;ribosome profiling;Ribosomes;Role;Site;Specificity;stem;Stress;Techniques;termination factor;Training;Transfer RNA;Translating;translation factor;Translations;Work

PROJECT_TITLE: Unraveling context specificity of translation by elucidating the mechanism of action of auxiliary translation factors


ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: We combine structural, biophysical, and biochemical techniques to probe the relationships between macromolecular structure, dynamics, and function. We are particularly interested in studying these relationships in large protein-nucleic acid complexes involved in biological processes such as DNA damage repair and mRNA cleavage and polyadenylation. Through the characterization of the three-dimensional structures, protein motions, and biological functions for such protein complexes, our research program will encourage a richer appreciation for how these complexes function in the cell and how alterations in structure and/or dynamics from mutation could lead to disease.

PI_NAMEs: LATHAM, MICHAEL PARKER (contact)

PROJECT_TERMS: Biochemical;Biological Assay;Biological Process;biophysical techniques;Biophysics;cancer type;Cells;cerebral degeneration;Communication;Complex;Disease;DNA biosynthesis;DNA Double Strand Break;DNA Repair;Double Strand Break Repair;Genetic Anticipation;Goals;immunodeficiency;in vivo;interest;Ionizing radiation;Kinetics;Messenger RNA;Modeling;Molecular Structure;Motion;Mutation;NBS1 gene;Nerve Degeneration;NMR Spectroscopy;nucleic acid binding protein;Nucleic Acids;Play;Polyadenylation;Population Heterogeneity;programs;protein complex;Protein Dynamics;Proteins;rational design;Repair Complex;Research;response;Rest;Role;Signal Transduction;structural biology;Structural Models;Structure;Techniques;Telomere Maintenance;three dimensional structure;tumorigenesis;Work

PROJECT_TITLE: Structural Biology Studies of a Large DNA Repair Complex


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Immunotherapy;Infectious Diseases;Kidney Disease;Lung;Organ Transplantation;Prevention;Transplantation;Vaccine Related

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE SARS-CoV-2 is transitioning from pandemic status to becoming an endemic virus, like influenza, and seasonal vaccinations will likely become the primary method for limiting disease. Despite the overall effectiveness of vaccination against SARS-CoV-2, some people are at increased risk of not developing protective immunity, most notably immunocompromised populations such as solid organ transplant recipients on life-long immunosuppressive medications. This research aims to determine how immune dysregulation before vaccination, driven by differences in mycophenolate mofetil immunosuppressive treatment, impacts the development and long-term maintenance of protective immunity against SARS-CoV-2, and ultimately how this dysregulation can be corrected to improve responses to vaccination in this and other at-risk populations.

PI_NAMEs: REED, ELAINE F (contact)

PROJECT_TERMS: 2019-nCoV;Acute;adaptive immune response;Address;Antibodies;Antibody titer measurement;B-Lymphocytes;Biological Assay;biological systems;Cells;Cellular Immunity;Clinical;Clinical Trials;Computer Models;COVID-19 booster;COVID-19 vaccination;Data;Development;Disease;DNA Methylation;Dose;Effectiveness;Enrollment;General Population;Generations;Goals;high risk;Humoral Immunities;Immune;Immune response;Immune system;Immune System Diseases;Immunity;Immunocompromised Host;Immunologics;Immunosuppressive Agents;Immunotherapy;Impairment;improved;Individual;Infection;Influenza;Kidney Transplantation;Knowledge;Leukocytes;Maintenance;Methods;methylation pattern;Morbidity - disease rate;mortality;mycophenolate mofetil;organ transplant recipient;Organ Transplantation;pandemic disease;pandemic virus;Patients;Peripheral;Peripheral Blood Mononuclear Cell;Persons;Pharmaceutical Preparations;Phase;Plasma;Population;Populations at Risk;prediction algorithm;predictive signature;prevent;recruit;Research;response;Risk;SARS-CoV-2 antibody;SARS-CoV-2 immunity;Seasons;Secondary Immunization;Severe Acute Respiratory Syndrome;Solid;Systems Analysis;T cell response;T-Cell Proliferation;Testing;Therapeutic immunosuppression;tool;Transplant Recipients;Vaccination;vaccination strategy;vaccine efficacy;vaccine immunogenicity;vaccine response;Vaccines;Variant;Virus

PROJECT_TITLE: Systems analyses of induction and maintenance of immunity to SARS-CoV-2 vaccination in kidney transplant recipients receiving mycophenolate mofetil immunotherapy


NIH_SPENDING_CATS: Genetics;Infectious Diseases;Sexually Transmitted Infections

ORG_CITY: OMAHA

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative Improving our knowledge of the structure and mechanisms of human and herpesvirus DNA replication machineries have tremendous significance for the future of medicine. Structure-based design of anticancer compounds targeting human DNA replication is underway, and the data generated by Project 1 will enable the development of drugs selective to viral, bacterial, and potentially yeast polymerases—but not human proteins. Successful completion of Project 2 will foster the discovery of novel medicines for treating a wide range of diseases caused by human herpesvirus and will also facilitate finding solutions to address the problem of drug resistance in these infections.

PI_NAMEs: TAHIROV, TAHIR H (contact)

PROJECT_TERMS: Address;anti-cancer;C-terminal;comparative;Complex;Data;design;Development;Disease;DNA;DNA biosynthesis;DNA Primase;DNA Primers;DNA replication fork;DNA-Directed DNA Polymerase;drug development;Drug resistance;Event;Family;Fostering;Foundations;Future;Genome;helicase;Herpesviridae;Herpesviridae Infections;Herpesvirus 1;Human;human DNA;Human Genome;improved;Infection;inhibitor;Knowledge;Laboratories;Life;Medicine;member;novel;novel therapeutics;Polymerase;polymerization;Polymers;Process;Proteins;RNA;Role;SS DNA BP;Structure;success;Viral;viral DNA;Virus Replication;Yeasts

PROJECT_TITLE: DNA Replication Machines: Structure-Function Studies


ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

ORG_STATE: CA

PHR: The T32 postdoctoral training program of the Scripps Research CTSA aims to establish a new generation of early career scientists capable of bridging science and medicine in the context of a rapidly changing world of healthcare and emerging diseases. Basic science, elucidation of mechanisms of diseases, discovery of new therapeutic approaches and drugs, and digital monitoring of health are primary areas of investigation for our members. In addition, an important component of citizenship is included in our training to promote three important core competencies: (i) mentorship, (ii) inclusion of all groups regardless of gender, racial, and cultural backgrounds, and (iii) community engagement.

PI_NAMEs: LAMIA, KATJA A (contact);TEYTON, LUC

PROGRAM_OFFICER_NAME: CONROY, JENNIE LYNN

PROJECT_TERMS: Postdoctoral Fellow;Research Institute

PROJECT_TITLE: CTSA Postdoctoral T32 at The Scripps Research Institute


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative - Overall Tulane National Primate Research Center (TNPRC) has one of the largest specific pathogen free (SPF) rhesus monkey breeding colonies in the US, a resource that has provided animals for NIH funded research projects for several decades and is a critical component of the Center's successful research program. Over half of all research projects at TNPRC are initiated by outside investigators, making this resource essential to the success of many NIH-funded researchers across the country. Experienced leadership and significant infrastructure investment, combined with proven techniques in breeding colony management, ensure continued responsible stewardship of this nationally recognized resource.

PI_NAMEs: RUSSELL-LODRIGUE, KASI E (contact)

PROGRAM_OFFICER_NAME: SUI, YONGJUN

PROJECT_TERMS: 2019-nCoV;Acquired Immunodeficiency Syndrome;Address;Animals;Award;base;Behavioral;Breeding;Caring;Clinical;Communities;congenital infection;Country;demographics;Development;Emerging Communicable Diseases;Ensure;experience;Funding;Funding Opportunities;Genetic;genetic analysis;genetic testing;germ free condition;Goals;Grant;Growth;HIV/AIDS;Human Resources;improved;Income;Individual;Infectious Agent;Infrastructure;Investigation;Investments;Leadership;Macaca;Macaca mulatta;Maintenance;Measles virus;Medical;Monitor;nonhuman primate;offspring;Opportunistic Infections;Pathology;Population;Population Genetics;Population Sizes;Primates;Production;Program Description;programs;repaired;Research;Research Personnel;Research Project Grants;Resources;Sales;Specific qualifier value;success;Techniques;Testing;Time;Trypanosoma cruzi;United States;United States National Institutes of Health;vaccine development;Viral;Virus;virus testing;Wages;Writing

PROJECT_TITLE: Maintenance of an SPF Macaque Breeding Colony for AIDS Research


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

PI_NAMEs: BOHM, RUDOLF PAUL (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;animal care;Animals;Area;Award;Behavioral;Breeding;Caring;Clinical;clinical care;Decision Making;demographics;Diagnostic Services;Ensure;experience;Fostering;Funding;Genetic;germ free condition;Goals;Grant;HIV/AIDS;Housing;improved;Income;Infectious Agent;Laboratories;Literature;Macaca;Macaca mulatta;Maintenance;Managed Care;Medical;Monitor;operation;Pathology;Philosophy;Population;Preventive Medicine;Primates;Production;programs;Recording of previous events;Research;Research Personnel;Research Project Grants;Resources;Sales;Services;Source;success;United States;United States National Institutes of Health;virus testing

PROJECT_TITLE: Husbandry and Management Core

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AARR-J]


ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: PROJECT NARRATIVE Most common human diseases are difficult to study because they are genetically complex. Conducting human genetic studies that include enough subjects with sufficiently detailed data to make definitive conclusions remains challenging, despite significant advances in genome technologies (e.g. DNA sequencing and editing). Most of these obstacles can be overcome by using standardized, genetically diverse laboratory mice, which offer known and reproducible genetic and phenotypic variation. The goal of the Special Mouse Strain Resource at The Jackson Laboratory is to: i) maintain and distribute these unique mouse populations to the biomedical research community, ii) further develop advanced resources for systems genetics and, iii) to provide leadership in best practices for research and reproducibility.

PI_NAMEs: LUTZ, CATHLEEN M;MURRAY, STEPHEN A (contact)

PROGRAM_OFFICER_NAME: MIROCHNITCHENKO, OLEG

PROJECT_TERMS: Address;Animals;Archives;biobank;Biological;Biomedical Research;Breeding;Caring;Cells;Certification;Collaborations;Collection;Communities;Complex;Consomic Strain;cost;Data;Derivation procedure;design;Development;Disease;Dissection;DNA sequencing;embryo cryopreservation;Ensure;Environmental Risk Factor;Epigenetic Process;Faculty;Foundations;Funding;Future;gene environment interaction;Genes;Genetic;Genetic Drift;Genetic Engineering;Genetic Epistasis;Genetic Heterogeneity;genetic manipulation;Genetic Research;genetic resource;Genetic study;Genetic Variation;Genome;Genotype;Geography;Goals;Health;Health Status;Heritability;Human;Human Biology;human disease;Human Genetics;Inbred Strain;Inbreeding;Infrastructure;Institution;Investments;Laboratories;Laboratory mice;Leadership;Legal;Maps;Medical Records;member;model design;Modeling;Mouse Strains;Mus;outreach;personalized medicine;Phenotype;Physiological;Play;Population;preservation;Production;Qualifying;Quantitative Trait Loci;Quarantine;Recombinants;repository;Reproducibility;Request for Proposals;Research;Research Personnel;Resources;Role;Sample Size;Source;sperm cell;Standardization;System;Technology;The Jackson Laboratory;Tissues;tool;trait;United States National Institutes of Health;Variant;Vendor;Work

PROJECT_TITLE: Special Mouse Strains Resource

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-P(55)R]


PI_NAMEs: LUTZ, CATHLEEN M (contact)

PROJECT_TERMS: Adopted;Age;Archives;avatar models;Breeding;Businesses;Clinic;Collection;Communities;Complex;Consomic Strain;cost;Cryopreservation;Development;Disease;Ensure;experimental study;functional genomics;Funding;Future;gene function;Gene Mutation;Genes;Genetic;Genetic Models;Genetic Research;genetic resource;Genetic study;Genetic Variation;Genotype;Goals;Hand;Health;Health Status;Housing;Human;Human Biology;human disease;Human Genetics;Hybrids;Inbred Strain;Inbreeding;Individual;informatics tool;Investigation;Maps;Mendelian disorder;Modeling;Mouse Strains;Mus;Phenotype;Play;Population;Quality Control;Quantitative Trait Loci;Recombinants;Reproducibility;Research Personnel;Research Project Grants;Resource Informatics;Resources;Role;Study models;success;System;The Jackson Laboratory;Time;tool;trait;Translating;Variant;Work

PROJECT_TITLE: Resource Core

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-P]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Clinical Research;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE Bacterial pneumonia leads to an uncontrolled response of the immune system that frequently causes lung injury/acute respiratory distress syndrome (ARDS). The molecular mechanism by which macrophages resolve infection-associated injury in the lung is not fully understood. Our research is aimed to support the novel concept that TRPV4 integrates the mechanical properties of the matrix and infectious signals to drive macrophage activation functions to protect the lung from injury.

PI_NAMEs: SCHERAGA, RACHEL GREENBERG (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Acute Respiratory Distress Syndrome;Alveolar;alveolar epithelium;Alveolar Macrophages;Alveolus;Bacterial Pneumonia;Binding;Binding Proteins;biophysical properties;Cations;Cell membrane;Cell Physiology;Cells;Chronic;Complex;cytokine;Cytoprotection;Cytoskeleton;Data;design;Disease;effective therapy;Effector Cell;Endothelium;epithelial injury;Goals;Heterogeneity;Homeostasis;Host Defense;Human;Immune;Immune response;In Vitro;in vivo;in vivo Model;Individual;Infection;Inflammatory;injured;Injury;innovation;interstitial;Invaded;Ion Channel;IRAK1 gene;Knockout Mice;Link;Location;loss of function;Lung;lung injury;Macrophage;Macrophage Activation;MAP Kinase Gene;MAPK8 gene;mechanical properties;mechanical signal;Mechanics;Medical;Mission;Modeling;Molecular;monocyte;mortality;Mus;new therapeutic target;novel;novel therapeutics;p38 Mitogen Activated Protein Kinase;p65;pathogen;Pathway interactions;Phagocytes;Phagocytosis;Pharmacological Treatment;Phenotype;Pneumonia;Process;Production;Property;Proteins;Proteomics;Pseudomonas aeruginosa;Pseudomonas aeruginosa pneumonia;Publishing;receptor;recruit;Research;Research Proposals;response;response to injury;Role;Signal Pathway;Signal Transduction;Signaling Molecule;Structure of parenchyma of lung;System;Tail;targeted treatment;Testing;therapy design;tissue injury;Tissues;TLR4 gene;TRPV channel;United States National Institutes of Health;Vanilloid

PROJECT_TITLE: TRPV4 Regulates Mechanosensitive Macrophage Functions in Lung Injury

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Neurosciences;Precision Medicine

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Narrative Transcutaneous vagal stimulation is an emerging, promising modality for atrial fibrillation, yet patient selection and stimulation parameters have not been optimized. This proposal will address these unmet needs by aiming to optimize the stimulation parameters of transcutaneous vagal stimulation and guide selection of the ideal candidates for this novel noninvasive therapy for atrial fibrillation, using physiological and biochemical biomarkers. By introducing an optimized treatment protocol for transcutaneous vagal stimulation, this approach has the potential to impact clinical practice and improve outcomes among a large number of patients.

PI_NAMEs: STAVRAKIS, STAVROS  (contact)

PROGRAM_OFFICER_NAME: TINSLEY, EMILY

PROJECT_TERMS: Ablation;Acute;Arrhythmia;Atrial Fibrillation;Atropine;Autonomic nervous system;Biochemical;Biochemical Markers;Biological Markers;Blood specimen;Cardiovascular system;Chronic;Clinical;clinical practice;Clinical Trials;clinically significant;Coronary sinus structure;Crossover Design;cytokine;Data;Dose;EKG P Wave;Electrocardiogram;Electrophysiology (science);experience;Experimental Models;Frequencies;health care delivery;Heart Atrium;heart rate variability;Hour;Human;improved;improved outcome;individual patient;Inflammatory;Infusion procedures;insight;Isoproterenol;Laboratories;Lead;Measures;metabolomics;Modality;Monitor;Morbidity - disease rate;Morphology;mortality;multidisciplinary;Myocardial;Neuromodulator;neuropeptide Y;novel;Pathogenesis;Patient Participation;Patient Selection;patient subsets;Patient-Focused Outcomes;Patients;Peripheral;Pharmaceutical Preparations;Physiological;placebo group;Play;Population;Randomized;randomized, clinical trials;Refractory;Regimen;Research Personnel;response;response biomarker;Role;Sampling;Series;Serum;side effect;smart watch;success;Surrogate Markers;Testing;tool;treatment optimization;Treatment Protocols;vagus nerve stimulation;Variant;Veins

PROJECT_TITLE: Biomarker-guided optimization of transcutaneous vagal stimulation for atrial fibrillation

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


PI_NAMEs: ALLERS, CAROLINA  (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Animals;Antigens;Biological Assay;Breeding;cost;Data;Detection;Development;diagnostic assay;Diagnostic Services;Future;Grant;interest;Laboratories;Macaca;Maintenance;Microbiology;Mission;nonhuman primate;offspring;pathogen;Pathogen detection;Performance;performance tests;Primates;programs;quality assurance;Research;Research Personnel;Research Support;Sampling;screening;Shipping;Simian Retroviruses;Site;SIV;Subgroup;success;Surveillance Program;targeted agent;Techniques;Testing;Time;United States National Institutes of Health;Validation;Validity of Results;Veterinary Medicine;Viral Physiology;Virus;virus testing;working group

PROJECT_TITLE: Viral Testing Core


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

PI_NAMEs: MURRAY, STEPHEN A (contact)

PROJECT_TERMS: Address;Alleles;Applied Research;Biological Process;Catalytic Domain;Cells;Communities;Complex;CRISPR/Cas technology;Cryopreservation;Development;Disease;DNA;DNA cassette;DNA Sequence;Docking;Electroporation;Embryo;Engineering;Ensure;Enterobacteria phage P1 Cre recombinase;Epitopes;ES Cell Line;Excision;experimental study;expression vector;Gene Activation;Gene Transfer Techniques;Genetic;genetic analysis;Genetic Engineering;genetic manipulation;Genetic Research;Genetic study;Genetic Variation;Genomics;Germ Lines;Goals;Heritability;Human;Human Biology;human disease;Human Genetics;In Vitro;Inbred Mouse;Inbred Strain;Inbreeding;Infrastructure;Integrase;Knock-in;Laboratories;Letters;Mediating;Microinjections;Modeling;Molecular;Mouse Embryonic Stem Cells;Mouse Strains;Mus;novel;Phenotype;Plasmids;Positioning Attribute;Process;Proteins;Quantitative Trait Loci;Recombinants;recombinase;Recommendation;repaired;Reporter;Reproducibility;Research;Research Design;Resources;RNA;Series;Site;Somatic Cell;Surveys;System;Terminator Codon;Tissues;tool;trait;Transgenes;Validation;validation studies;Variant;zygote

PROJECT_TITLE: Applied Research


NIH_SPENDING_CATS: Genetics;Lung

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: NARRATIVE Dendritic cells (DCs) play key roles in orchestrating immunity to pathogens. Multiple subsets of functionally specialized DCs exist, but DC function can also be modulated by microbial and tissue-derived stimuli. We have recently demonstrated a major role for the metabolic sensors mTOR and GCN2 in regulating DC development and function, and the underlying mechanisms of this “metabolic imprinting” will be explored.

PI_NAMEs: PULENDRAN, BALI  (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Ablation;adaptive immunity;Adoptive Transfer;Allergic;Allergic inflammation;Alveolar Macrophages;Amino Acids;Autophagocytosis;Bone Marrow;Cell Communication;Cell Physiology;cell type;Cells;Cellular biology;Chimera organism;conditional knockout;Data;Dendritic Cells;Development;EIF4EBP1 gene;Epigenetic Process;Epithelial Cells;FRAP1 gene;functional plasticity;gene repression;Genetic Transcription;gut inflammation;Hematopoietic;Homeostasis;Immune response;Immunity;imprint;In Situ;Infection;Inflammasome;Inflammation;insight;ITGAM gene;ITGAX gene;Knockout Mice;lipid metabolism;Lung;Lymphoid Cell;Macrophage;Mediating;Metabolic;metabolic profile;microbial;Modeling;Molecular;monocyte;mRNA Translation;mTOR Signaling Pathway;Mus;Natural Killer Cells;Nature;neutrophil;Organ;Outcome;pathogen;Pathway interactions;Phenotype;Play;programs;pulmonary function;receptor;response;Role;sensor;Signal Pathway;Signal Transduction;single cell ATAC-seq;Spleen;Starvation;Stimulus;Stress;Tissues;transcription factor;Vaccination;Viral;Work

PROJECT_TITLE: Metabolic imprinting of dendritic cell fate and function in tissues

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


PI_NAMEs: VALLENDER, ERIC J. (contact)

PROJECT_TERMS: Acceleration;Acquired Immunodeficiency Syndrome;Alleles;animal data;Animal Husbandry;Animals;Behavioral;Breeding;Budgets;Collaborations;Communication Tools;Communities;Data;data sharing;Databases;Decision Making;deep sequencing;design;Development;Disease Progression;DNA Library;Ensure;evidence base;exome sequencing;experience;Funding;Future;Genetic;genetic information;genetic pedigree;genetic resource;Genetic Services;genetic testing;Genetic Variation;Genome;genome sequencing;genomic data;genomic variation;Genomics;Genotype;Geographic Locations;Geography;Goals;Grant;Haplotypes;Health;HIV/AIDS;Immune response;improved;Inbreeding;Infection;Informatics;Institution;Macaca;Macaca mulatta;Maintenance;male;MHC Class I Genes;Mind;Monitor;nonhuman primate;Other Genetics;Output;Population;Predisposition;Preventive Medicine;Primates;Process;programs;Protocols documentation;reproductive;Research;Research Activity;Research Personnel;research study;Role;Scientist;Services;simian human immunodeficiency virus;SIV;Source;Structure;System;Targeted Research;Testing;testing services;Time;Translational Research;Visit;whole genome;Wisconsin;working group

PROJECT_TITLE: MHC Genetic Typing Core


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Paget's Disease;Rare Diseases

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative: Paget’s Disease (PD) is a common bone disease, characterized by highly localized pagetic bone lesions (PDLs) that result from local increases in bone destruction, followed by rapid formation of bone that is of poor quality. However, the mechanisms responsible for the highly focal nature of PDLs, why PD is diagnosed in elderly patients and why the lesions persist for long periods are unclear. This proposal will determine the role of osteocytes, a type of bone cell that comprises 95% of the bone cells in the adult skeleton and can persist for decades, in the development of PD and PDLs, which is currently is unknown.

PI_NAMEs: KURIHARA, NORIYOSHI  (contact)

PROGRAM_OFFICER_NAME: CHEN, FAYE H

PROJECT_TERMS: Adult;Affect;Age Years;Aging;Animal Model;Automobile Driving;bone;bone cell;Bone Development;Bone Diseases;Bone Resorption;Cells;Characteristics;Coupled;Coupling;Data;Dendrites;Development;Diagnosis;Disputes;DNA Sequence Alteration;Dose;Ephrin-B2;Etiology;Exposure to;Home;Homing;IGF1 gene;IL6 gene;in vivo;Innate Bone Remodeling;insight;Insulin-Like Growth Factor I;Interleukin-6;Lesion;Link;Location;Lytic;Measles virus;Measles virus nucleocapsid protein;Modeling;Molecular;Morphology;mouse model;Mouse Protein;Mus;Nature;old mice;older patient;Osteitis Deformans;osteoblast differentiation;Osteoblasts;Osteoclasts;Osteocytes;Osteogenesis;Osteolytic;overexpression;Paget's Disease;Paper;Pathogenesis;Patients;Phase;Population;Process;programs;promoter;protein expression;Proteins;Publications;Reporting;Role;Sampling;senescence;Signal Transduction;Site;skeletal;Skeleton;Tamoxifen;tartrate-resistant acid phosphatase;Testing;TNFSF11 gene;Transgenic Mice

PROJECT_TITLE: Osteoclast-Osteocyte Interaction's in Paget's Disease

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]