NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Networking and Information Technology R&D (NITRD);Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health;Telehealth;Vaccine Related

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE Understanding patient and provider responses to COVID-19 and disparities in the care received by patients is essential to inform immediate-term and longer-term policymaking designed to ensure that the U.S. health care system can resiliently provide adequate care for elderly and vulnerable patient populations. Leveraging the assets of the RAND U19 Center on Excellence (COE) on Health System Performance, which has built a multi- year data set of physician organizations (POs) nationally and their attributes, we propose to 1) Estimate how health services utilization changed during the COVID-19 pandemic, if unmet care needs are met in following years, how policy responses (social distancing policies and COVID-19 vaccination) impacted care, and disparities in unmet care among socially and clinical vulnerable patient populations; 2) Measure PO-level changes in the use of telehealth during and in the years following the COVID-19 pandemic and PO adoption of telehealth improves care outcomes; and 3) Estimate the extent of PO closures and consolidation on patient continuity of care and access to providers.

PI_NAMEs: WHALEY, CHRISTOPHER  (contact)

PROGRAM_OFFICER_NAME: NOVAK, PRISCILLA JOY

PROJECT_TERMS: access disparities;Adopted;Adoption;Affect;Businesses;Cantor;care delivery;care outcomes;Caring;Centers of Research Excellence;Characteristics;Clinical;Continuity of Patient Care;County;COVID-19;COVID-19 pandemic;COVID-19 pandemic effects;COVID-19 patient;COVID-19 vaccination;Data;Data Set;design;Disparity;Ensure;Equity;ethnic minority population;experience;Face;Fee-for-Service Plans;Financial Hardship;Financial Support;Funding;Health;health care delivery;health care disparity;health care service utilization;health service use;Health Services;Health Services Accessibility;Health system;Healthcare Systems;Hospitalization;improved;Investments;Lead;Long-Term Care for Elderly;Low income;Marketing;Measures;medical vulnerability;Medicare;Modality;multiple chronic conditions;Natural experiment;Operative Surgical Procedures;Organizational Change;organizational structure;Outcome;pandemic disease;pandemic impact;Patient Care;patient population;patient subsets;Patient-Focused Outcomes;Patients;Pattern;Patterns of Care;payment;Performance;Persons;Physicians;Policies;Policy Making;Population;Positioning Attribute;Privatization;Procedures;Provider;provider adoption;public health emergency;Publishing;Qualifying;Quality of Care;racial minority;racial minority population;Research Personnel;resilience;Resources;response;Risk Factors;Running;Rural;Rural Minority;SARS-CoV-2 exposure;Services;Shapes;Shock;social;Social Distance;social vulnerability;stay-at-home order;System;Technology;telehealth;Telemedicine;Travel;United States;United States Agency for Healthcare Research and Quality;United States Centers for Medicare and Medicaid Services;Variant;Visit;Work

PROJECT_TITLE: Health Care Utilization During the COVID-19 Pandemic

STUDY_SECTION: HSQE

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


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cardiovascular;Chronic Pain;Hematology;Lung;Lymphatic Research;Neurodegenerative;Neurosciences;Orphan Drug;Pain Research;Peripheral Neuropathy;Rare Diseases

ORG_CITY: DALLAS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROSCIENCES

ORG_FIPS: US

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative PIEZO channels are critical sensors of touch and pain (somatosensation), volume regulation (osmosensation), shear stress (cardiovascular tone), baroreception, proprioception and respiratory physiology, and may have other important functions. PIEZO dysfunction has been linked to diverse pathologies including hypertension, lymphatic disease and anemias, somatosensory and neurological disorders, cancer and metastasis, amongst others. Our research will provide a path to development of effective therapeutics targeting neuropathic pain, brain ischemia and gliomas, amongst others.

PI_NAMEs: SYEDA, RUHMA  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Anemia;Biochemical;Biological;Biological Assay;Biological Process;Biological Response Modifier Therapy;biophysical techniques;Brain Ischemia;Cardiovascular Diseases;Cardiovascular system;Cells;Coupled;Data;Development;Disease;Family;Functional disorder;Glioma;Goals;Human;Hypertension;interest;Investigation;Ion Channel;Ions;Link;Lipid Bilayers;Lipids;Lymphatic Diseases;Malignant Neoplasms;Mechanics;mechanotransduction;Medical;Membrane;Neoplasm Metastasis;Nervous System Disorder;Pain;painful neuropathy;Parents;patch clamp;Pathology;Piezo 1 ion channel;Piezo 2 ion channel;Piezo ion channels;pressure;Probability;Process;Proprioception;protein purification;Protocols documentation;reconstitution;Regulation;release of sequestered calcium ion into cytoplasm;Research;Research Proposals;Respiratory physiology;response;sensor;shear stress;single molecule;Somatosensory Disorders;Stress;System;therapeutic development;therapeutic target;therapeutically effective;Touch sensation;Vertebrates;voltage

PROJECT_TITLE: Permeation and Gating Mechanisms of Mechanosensitive PIEZO channels

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: ITHACA

ORG_DEPT: CHEMISTRY

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: Project Narrative This program will investigate the means by which metalloenzymes and transition metal complexes interact with reactive, or, “fixed” nitrogen species. Key research directions include understanding how organisms use fixed nitrogen species as part of their primary cellular energy transduction metabolisms. Reactive nitrogen species such as nitric oxide play vital roles in human health, in particular in controlling vasodilation––understanding how these species are generated and interconverted may help develop new therapeutic strategies for cardiac- related pathologies and for combatting infections.

PI_NAMEs: LANCASTER, KYLE M (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Acids;Address;Administrative Supplement;Ammonia;Archaea;Bacteria;Biochemistry;Bioinorganic Chemistry;Biology;Cardiac;Cell Respiration;Chemicals;Collaborations;Complex;Copper;Dioxygen;DNA-dependent protein kinase;Drug Metabolic Detoxication;electronic structure;Enzymatic Biochemistry;Enzymes;Goals;Health;Heme;Human;human pathogen;Hydroxylamine;Infection;instrumentation;Kinetics;Knowledge;Mass Spectrum Analysis;Metabolic;Metabolism;metal complex;metalloenzyme;Metals;Modeling;Molybdoferredoxin;Nitrates;Nitric Oxide;Nitrogen;Nitrogenase;Nitrous Oxide;novel therapeutic intervention;Organism;Oxidants;oxidation;Oxidation-Reduction;Pathology;Play;programs;Proliferating;Proteins;Proteomics;Protons;Reaction;Reactive Nitrogen Species;Research;Roentgen Rays;Role;Signal Transduction;Site;Spectrum Analysis;System;Transition Elements;Vasodilation;Work;X-Ray Crystallography

PROJECT_TITLE: Administrative Supplement (Instrumentation) for R35 GM124908: Bioinorganic Chemistry of Nitrogen


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Depression;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Services;Mental Health;Mental Illness;Opioid Misuse and Addiction;Opioids;Pain Research;Primary Health Care;Substance Misuse

ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

ORG_STATE: CA

PHR: NARRATIVE This pragmatic trial will test an innovative, scalable model of care management—provided by a nurse over the telephone—for primary care patients with opioid use disorder and depression in Washington state and New Mexico. The trial will test whether patients randomized to the nurse care management are more likely to receive sustained medication treatment for opioid use disorder, and more likely to have clinically significant reduction in symptoms of depression, over the following 12 months.

PI_NAMEs: BRADLEY, KATHARINE ANTHONY;DEBAR, LYNN L. (contact)

PROGRAM_OFFICER_NAME: RUDORFER, MATTHEW V

PROJECT_TERMS: Accident and Emergency department;addiction;Adverse event;Age;alcohol use disorder;Anxiety;Buprenorphine;Care given by nurses;Caring;Case Manager;Cessation of life;chronic pain;chronic painful condition;Clinic;Clinical;Clinical Trials;clinically significant;collaborative care;common treatment;comorbidity;compare effectiveness;comparison group;Consent;depression model;Depression screen;depressive symptoms;design;Development;effectiveness trial;electronic health data;Electronic Health Record;Elements;Eligibility Determination;Enrollment;Ethnic Origin;evidence base;Evidence based treatment;follow-up;formative assessment;Hospitalization;implementation evaluation;implementation process;Improve Access;improved;improved outcome;incremental cost;Injectable;innovation;insurance claims;Intention;Intervention;Managed Care;Massachusetts;Measures;Mediator;medication for opioid use disorder;Mental Depression;Mental Health;Methods;Modeling;Naltrexone;New Mexico;novel;Nurses;Nursing Care Management;Opioid;opioid epidemic;opioid overdose;opioid use disorder;Outcome;Overdose;Pain;Patient Care;patient oriented;Patient-Focused Outcomes;Patients;Persons;Pharmaceutical Preparations;Phase;Post-Traumatic Stress Disorders;practice setting;pragmatic trial;prescription monitoring program;Prevalence;Primary Care;primary care clinic;primary care patient;primary care practice;primary care provider;primary care setting;primary care team;primary outcome;Procedures;programs;Proprotein Convertase 2;Public Health;Race;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recovery;recruit;Research Personnel;Resolution;retention rate;Role;routine screening;Rural;Sampling;secondary outcome;Self-Injurious Behavior;shared decision making;Site;Sleeplessness;social stigma;substance use;Substance Use Disorder;suburb;Suicide attempt;Symptoms;System;Telephone;Testing;Time;treatment as usual;trial enrollment;Universities;uptake;usual care arm;Washington

PROJECT_TITLE: Patient-centered team-based primary care to Treat Opioid Use Disorder, Depression, and Other conditions


ORG_CITY: AMES

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: IOWA STATE UNIVERSITY

ORG_STATE: IA

PI_NAMEs: SASHITAL, DIPALI GURUDUTT (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Administrative Supplement;Affinity;Award;biophysical analysis;biophysical techniques;Biotechnology;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Contract Services;cost;Cryoelectron Microscopy;Data Analyses;Equipment;Fees;Funding;Immunity;instrument;instrumentation;Iowa;Macromolecular Complexes;Measurement;Measures;operation;parent grant;Recurrence;Research;Research Support;Sampling;screening;stoichiometry;Training;United States National Institutes of Health

PROJECT_TITLE: Defining mechanisms of diverse CRISPR-Cas complexes


ORG_CITY: EAST LANSING

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE This proposal focuses on the structure and function of metal ion receptors that translate fluctuations in zinc concentration into changes in cellular processes. These metalloprotein studies will characterize the fundamental zinc-receptor proteins that control cell cycle progression. This proposal will also develop emerging physiochemical methods and new chemical probes to characterize the zinc fluxes that ultimately govern cellular growth and division.

PI_NAMEs: O'HALLORAN, THOMAS V (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: absorption;Binding Sites;Biochemical;Biochemistry;Catalysis;Cell Cycle;Cell Cycle Progression;Cell Cycle Regulation;cell growth;Cell Physiology;Cells;Chemicals;cofactor;Data;Disease;emission spectroscopy;Environment;Enzymes;Event;Fertilization;genetic regulatory protein;Human;Immune response;Inorganic Chemistry;insulin secretion;Ions;live cell imaging;Mammalian Cell;Mass Spectrum Analysis;Mediating;Meiosis;Metalloproteins;Metals;Methods;Molecular;Movement;Neurons;Pathway interactions;Physiology;Process;Protein Biochemistry;protein structure;Proteins;receptor;response;Roentgen Rays;Role;Signal Transduction;Spectrum Analysis;Structure;Techniques;Testing;tool;trafficking;Translating;Zinc

PROJECT_TITLE: Regulatory Roles of Zinc Fluxes in Metalloprotein Occupancy and Cell Cycle Progression


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: PITTSBURGH

ORG_NAME: CARNEGIE-MELLON UNIVERSITY

ORG_STATE: PA

PI_NAMEs: PITKOW, ZACHARY SAMUEL (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TITLE: CRCNS: Neural computations for continuous control in virtual reality foraging


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: NOVATO

ORG_NAME: BUCK INSTITUTE FOR RESEARCH ON AGING

PHR: PROJECT NARRATIVE Delirium is a devasting acute confusional state that is common in older adults after surgery or in the hospital, especially with Alzheimer's disease. This project investigates the molecular mechanisms that link inflammation to impaired metabolism in delirium and Alzheimer's disease, and how small molecule metabolites with roles in aging might lead to metabolic therapies for delirium.

PI_NAMEs: NEWMAN, JOHN C (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acute;Affect;Age;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;analog;APP-PS1;Area;Attention;Basic Science;Behavior;Behavioral;beta-Hydroxybutyrate;Biological Markers;Biology;Biology of Aging;Brain;Cells;Cerebrospinal Fluid;Cerebrum;Chronic;Clinical;clinical development;Clinical Research;Cognitive deficits;cohort;Cohort Studies;Compensation;Confusion;Conscious;Consumption;Cultured Cells;Data;Delirium;Dementia;Development;disability;drug discovery;Elderly;Encephalitis;Energy Metabolism;Energy-Generating Resources;Enzyme Induction;Enzymes;Failure;Fasting;Functional disorder;Genetic Models;Geroscience;glial activation;Glucose;glucose metabolism;Goals;high risk;Hospitalization;Hospitals;Human;Hypoxia;Impairment;improved;In Vitro;in vitro Model;in vivo;Induced Neurons;Infection;Inflammasome;Inflammation;Inflammatory;Injections;innovation;Intervention;ketogenic diet;Ketone Bodies;Ketones;Knock-out;Knockout Mice;Link;Lipopolysaccharides;Macrophage;Macrophage Activation;Mediator;Memory;Metabolic;Metabolic dysfunction;Metabolism;Microglia;Modeling;Molecular;mortality risk;mouse model;Mus;NAD+ Nucleosidase;neuroinflammation;Neuronal Dysfunction;Neurons;Nicotinamide adenine dinucleotide;older adult;Operative Surgical Procedures;Oxidative Stress;Pathway interactions;Patients;Peripheral;Persons;Pharmaceutical Preparations;Pharmacological Treatment;Phenotype;physiologic stressor;postoperative delirium;Postoperative Period;Predisposition;prevent;Prevention;resilience;Risk;Role;Sampling;sedative;Signal Transduction;small molecule;Surgical complication;Syndrome;System;Testing;theories;Work

PROJECT_TITLE: Geroscience metabolites beta-hydroxybutyrate and NAD+ linking inflammation and neuroenergetic failure in delirium


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PI_NAMEs: SAUCERMAN, JEFFREY J. (contact);WOLF, MATTHEW J

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Cardiac Myocytes;Cardiac Output;Cells;Computer Models;Data;drug candidate;Drug Combinations;Drug Modulation;drug repurposing;Drug usage;FDA approved;Funding;Goals;Heart failure;Heart Hypertrophy;Human;Hypertrophy;In Vitro;in vivo;insight;Modeling;mouse model;muscle form;Myocardium;network models;parent grant;Pharmaceutical Preparations;pharmacologic;Pharmacology;predictive modeling;Rattus;Regulation;Signal Transduction;Signaling Molecule;System;Testing;therapeutic target;Translating

PROJECT_TITLE: Diversity Supplement:  Systems Pharmacology Model of Cardiac Hypertrophy


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Digestive Diseases;Liver Disease;Lung;Organ Transplantation;Transplantation

ORG_CITY: CHICAGO

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Lung tissue removed for transplantation currently cannot be preserved for more than 8 hours, and even then, damage to the lung tissue likely contributes to the low survival rate following lung transplantation (50% of patients do not survive more than 5 years). Our studies seek to improve lung tissue preservation and transplant outcomes; we will test using a liver cell bioreactor to improve lung tissue metabolism and reduce inflammation while the lungs are being transported for transplantation. Ultimately, our work will address current limitations in lung transplantation by helping to extend donor organ transportation time and distance beyond 8 hours and to improve post-transplant patient survival.

PI_NAMEs: GERLACH, JOERG C.;SANCHEZ, PABLO G (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: Address;Biochemical;Biological;Biomedical Engineering;Bioreactors;Blood specimen;Cadaver;cell injury;Cell Physiology;Cells;Chronic;Circulation;clinically significant;Conditioned Culture Media;Cross Circulation;Cryopreservation;cytokine;Cytokine Signaling;Data;Drug Metabolic Detoxication;Endothelium;Experimental Models;experimental study;Family suidae;Genetic;Genetic Transcription;graft dysfunction;Hepatic;Hepatocyte;Histologic;Hour;Human;human model;improved;In Vitro;in vitro testing;in vivo;in vivo evaluation;Individual;Inflammation;Inflammatory;inhibitor;Injury;Intervention;Investigation;Ischemia;liver function;liver injury;Lung;lung preservation;Lung Transplantation;Measures;Metabolism;Mitochondria;Modeling;mortality;National Heart, Lung, and Blood Institute;Nuclear;Organ;Organ Donor;Outcome;Patients;Perfusion;pharmacologic;Phenotype;Play;post-transplant;preservation;pulmonary function;Rattus;Reaction;receptor for advanced glycation endproducts;Regulation;Research;response;Resuscitation;Risk;Risk Factors;Role;Running;Signal Pathway;Signal Transduction;Structure of parenchyma of lung;Survival Rate;Technology;Testing;Time;Tissue Preservation;Tissue Transplantation;Tissue Viability;Tissues;transplant model;Transplant Recipients;Transplantation;Transportation;United States National Institutes of Health;usability;Vascular Endothelium;ventilation;Waiting Lists;Work

PROJECT_TITLE: Incorporating hepatic cell function into lung ex vivo lung perfusion for transplant preservatio

STUDY_SECTION: SAT

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


ADMINISTERING_IC: CA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;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;Prevention;Primary Health Care;Rehabilitation;Rural Health;Social Determinants of Health

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: NARRATIVE There are more than 18 million cancer survivors in the U.S., approximately 20% of which live in rural communities. This study will assess facilitators and barriers to implementing the National Standards for Cancer Survivorship Care in rural health systems. The findings will inform education and outreach efforts in the Consortium Catchment area as well as future research to promote implementation of high-quality, accessible survivorship care in rural health systems nationally.

PI_NAMEs: LYNCH, THOMAS JAMES (contact)

PROGRAM_OFFICER_NAME: HE, MIN

PROJECT_TERMS: Address;American Cancer Society;barrier to care;behavioral health;Cancer Center;Cancer Center Support Grant;Cancer Control;cancer health disparity;Cancer Survivor;Cancer Survivorship;cancer survivorship care;Caring;Catchment Area;Clinical;Communities;community engagement;Community Outreach;Complex;contextual factors;critical access hospital;Data Collection;design;Disparity;Education and Outreach;Ensure;Equity;experience;Federally Qualified Health Center;Geography;Goals;health care availability;health disparity;health equity;health information technology;Health Personnel;Health system;implementation barriers;implementation design;implementation framework;implementation science;implementation strategy;improved;Individual;informant;interest;Intervention;Interview;Malignant Neoplasms;medical specialties;Nurses;Oncologist;Outcome;outreach;patient navigator;Patients;Physician Executives;Policies;primary care provider;Process;Provider;Qualitative Research;Quality of Care;recruit;Research;Research Methodology;Research Personnel;response;Rural;Rural Community;rural counties;Rural Health;rural health clinic;Rural Population;rural setting;Scientist;Structure;success;survivorship;Universities;Washington;Work

PROJECT_TITLE: CCSG Supplement: Assessing Facilitators and Barriers to Implementation of the National Survivorship Care Standards in Rural Health Systems


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE The proposed work seeks to answer important outstanding questions about the function and regulation of the actin cytoskeleton using infectious microbes as cell-biological tools. The actin cytoskeleton plays critical roles in basic cell features and behaviors including shape, migration, division, and intracellular transport, and its misregulation is a crucial contributor to pathogenesis, for example, in inflammation, cardiovascular disease, cancer metastasis, and microbial infection. Therefore, understanding actin regulation and function may lead to new approaches for diagnosing and treating human disease.

PI_NAMEs: WELCH, MATTHEW D (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Actins;Address;Baculoviruses;Behavior;Biochemical;Biological;Biological Process;Burkholderia;Cardiovascular Diseases;cell behavior;Cell Communication;Cell fusion;Cell membrane;Cell Nucleus;Cell Physiology;Cells;Cellular biology;Cytoplasm;Cytoskeleton;Diagnosis;Disease;Event;Extracellular Matrix;Functional disorder;Funding;Gene Expression;Genetic;host colonization;host-microbe interactions;Human;human disease;imaging approach;Infection;Inflammation;insight;Intracellular Transport;Knowledge;Membrane;Methods;Microbe;microbial;Microbiology;migration;Modeling;Molecular;Movement;Mycobacterium marinum;National Institute of General Medical Sciences;Neoplasm Metastasis;novel strategies;Nuclear;Nuclear Envelope;Nucleopolyhedrovirus;Pathogenesis;Play;polymerization;Polymers;Positioning Attribute;prevent;Property;Regulation;Research;response;Role;Shapes;tool;Work

PROJECT_TITLE: Microbial mobilization of the actin cytoskeleton


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_DEPT: PHARMACOLOGY

PHR: Project Narrative This application for administrative supplemental grant is to request fund for purchasing an Octet R2 Biolayer Interferometry (BLI) system for measuring protein-protein interactions in the receptor/ligand systems that the parent grant studies.

PI_NAMEs: ZHANG, XUEWU  (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Acceleration;Administrative Supplement;Affinity;antibody libraries;Binding;Calorimetry;Cardiovascular system;Complex;Core Facility;Development;Electrons;Event;Funding;Future;Grant;heparin proteoglycan;high throughput screening;Human Cell Line;Immune system;Interferometry;KDR gene;Kinetics;Label;Ligands;Light;Measurement;Measures;Mediating;Medical center;Membrane;Microscopic;mutant;nanomolar;Nervous System Physiology;parent grant;parent project;Parents;plexin;Polysaccharides;protein protein interaction;Proteins;receptor;Receptor Activation;Sampling;small molecule;Structure;Surface;System;Techniques;Titrations

PROJECT_TITLE: Request for administrative fund for purchasing of a Biolayer Interferometry (BLI)


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Lupus;Prevention

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: PROJECT NARRATIVE The successful completion of the MONA-LISA project will provide detailed knowledge of the immunological, genomic, and metabolic characteristics of people who are at risk for the development of systemic lupus erythematosus and subsequently go on to develop the disease. This will enable clinical researchers to develop better clinical trials to test novel therapies that prevent the development of autoimmune diseases such as lupus. These data will also allow health care providers to better diagnose patients with early lupus features before they develop permanent organ damage and disability.

PI_NAMEs: GUTHRIDGE, JOEL MARVIN;KARP, DAVID R (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: Administrative Supplement;Anti-malarials;Atlases;Autoimmune;Autoimmune Diseases;Autoimmunity;B cell repertoire;Black American;Black Populations;Categories;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Characteristics;Classification;Clinical;Clinical assessments;Clinical Data;clinical development;Clinical Trials;cohort;Data;Development;Diagnosis;diagnostic tool;disability;Disease;disorder prevention;DNA;Double-Blind Method;effective intervention;Enrollment;Epidemiology;epigenomic profiling;epigenomics;Ethnic Population;Evolution;Funding;Gene Expression Regulation;Genetic Complementation Test;Genomics;Genotype;Goals;Health Personnel;Hispanic Americans;Hydroxychloroquine;Immune;Immune response;Immune system;Immunologics;Immunophenotyping;Individual;Inflammation Mediators;Insulin-Dependent Diabetes Mellitus;Intervention Trial;Knowledge;Learning;lipid mediator;lipidomics;Lipids;Lupus;Lupus Erythematosus;Mediator;Messenger RNA;Metabolic;metabolome;metabolomics;Methodology;Mononuclear;multiple omics;National Institute of Allergy and Infectious Disease;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;Native American population;new therapeutic target;next generation sequencing;novel;novel diagnostics;novel therapeutics;Organ;Participant;Pathogenesis;Pathway interactions;Patient Outcomes Assessments;Patients;Performance;peripheral blood;Peripheral Blood Mononuclear Cell;Persons;phase 2 study;Placebo Control;Plasma;Populations at Risk;prevent;prognostic tool;programs;progression risk;prospective;Randomized;recruit;Reporting;Research Personnel;Resolution;Resources;Rheumatoid Arthritis;Risk;Risk Assessment;risk variant;RNA;Sampling;Serum;single-cell RNA sequencing;skin disorder;Specimen;Standardization;Systemic Lupus Erythematosus;Systems Analysis;T-Lymphocyte;Testing;therapeutic target;Time;tool;transcriptomics;Urine;Variant;Whole Blood

PROJECT_TITLE: Supplement to Mechanisms of New-Onset Autoimmunity/Longitudinal Immune Systems Analysis (MONA-LISA)


ADMINISTERING_IC: EY

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Prevention;Wound Healing and Care

ORG_CITY: SYRACUSE

ORG_NAME: DUB THERAPEUTICS INC.

PHR: Narrative: Worldwide, poor healing from mechanical or surgical wounds, infections, and ulcers are an unmet clinical need. Tissue regeneration has a common mechanistic underpinning between different tissues. The current project will test our novel topical self-delivery siRNA-based therapeutic in an in vivo dermal wound healing pig model and in ex vivo human skin equivalents. These studies will set the stage for indication expansion to other wound healing applications.

PI_NAMEs: WILLIAMS, TERE M. (contact)

PROGRAM_OFFICER_NAME: GOVER, TONY DOUGLAS

PROJECT_TERMS: Adrenal Cortex Hormones;Adverse event;Affect;animal efficacy;Biological Products;blind;Blindness;Cataract;Cholesterol;Cicatrix;Clinical;Cornea;corneal scar;Cyclic GMP;Defect;Dose;Economic Burden;efficacy study;Encapsulated;Environment;Epithelium;experimental study;Eyedrops;Family suidae;Fibroblasts;first-in-human;Funding;Glaucoma;healing;Human;improved;in vivo;Infection;Injury;Investments;Keratoplasty;knock-down;manufacturing process;manufacturing run;manufacturing scale-up;Marketing;Mechanics;Modeling;monocular;Mus;novel;nuclease;Organ Culture Techniques;Oryctolagus cuniculus;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Phase;Phase I Clinical Trials;Population;porcine model;Preparation;prevent;Prevention;Quality of life;Resistance;response;Safety;siRNA delivery;Skin;Skin wound healing;Small Business Innovation Research Grant;Surgical wound;Testing;Therapeutic;therapeutic siRNA;tissue regeneration;Tissues;Toxicology;Transplantation;Trauma;ubiquitin isopeptidase;Ulcer;Visual impairment;Work;wound healing;Wound models

PROJECT_TITLE: A single dose anti-scarring therapeutic for the cornea

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(12)-B]


NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Genetics;Neurodegenerative;Orphan Drug;Rare Diseases

PHR: Project Narrative Our goal is to understand the recognition of nucleic acids inside cells. One focus will be RNA- mediated recognition in cell nuclei. We will use our understanding of mechanism to develop new methods to control expression of genes involved in disease, including the genes responsible for Friedreich's Ataxia and Fuchs' Dystrophy.

PI_NAMEs: COREY, DAVID R (contact)

PROJECT_TERMS: Affect;Area;Biological Process;Biological Response Modifier Therapy;Cell Line;Cell Nucleus;Cell Physiology;Cells;Cellular biology;cellular targeting;Chemicals;Chemistry;Complex;Corneal Endothelium;crosslink;Cytoplasm;Degenerative Disorder;Disease;drug development;Family;Friedreich Ataxia;Fuchs' Endothelial Dystrophy;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Human;Immunoprecipitation;insight;Knock-out;Laboratories;Mass Spectrum Analysis;Mediating;Medicine;Methods;MicroRNAs;Modification;mutant;novel;Nuclear;nucleic acid structure;Nucleic Acids;Oligonucleotides;patient population;Peer Review;Pharmaceutical Preparations;Proteins;Publications;Regulation;RNA;RNA Interference;RNA Splicing;Role;synthetic nucleic acid;therapeutic development;tool;transcriptome sequencing;Translations;Trinucleotide Repeats;Untranslated RNA;Validation;Work

PROJECT_TITLE: Recognition of Cellular Targets by single and double-stranded nucleic acids


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

ORG_CITY: TEMPE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: Project Narrative This project is focused on the molecular-genetic mechanisms associated with the evolution of genetic variation, diversification of phenotypes, and the consequences for organismal fitness. The research will: 1) generate a comprehensive understanding of the rates at which cellular errors arise at the DNA, RNA, and protein levels across the Tree of Life and develop theory to explain the patterns; 2) further establish the Daphnia model system to help understand the evolutionary features of genes involved in key functions such as translation, bioenergetics, environmental sensing, and lifespan determination; and 3) develop theory to explain scaling patterns in the emerging field of evolutionary cell biology and the mechanisms by which cells evolve.

PI_NAMEs: LYNCH, MICHAEL R (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Amino Acids;Architecture;asexual;Attention;Automobile Driving;Bioenergetics;Biological Models;Cells;Cellular biology;Collection;Crustacea;Daphnia;design;DNA;Environment;Evolution;fitness;Gene Structure;Genes;Genetic;Genetic Drift;genetic evolution;Genetic Recombination;Genetic Variation;Genome;Genomics;Genotype;Health;Human;insight;Joints;Life;life span;male;Meiotic Recombination;Messenger RNA;Methods;Mitochondria;Modeling;Molecular;Molecular Genetics;Mutation;Natural Selections;Nuclear;Ovum;Pattern;Pest Control;Phenotype;Phylogenetic Analysis;Play;Population;Population Genetics;prevent;Production;protein aggregation;Proteins;Proteomics;Research;Ribosomes;RNA;Role;sex determination;Sexual Reproduction;Structure;Surveys;System;Testing;theories;Toxic effect;trait;Translations;Trees;Variant;Work

PROJECT_TITLE: Causes and Population-genetic Consequences of Molecular Variation


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: Newark

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: The treatment of human disease is highly dependent on efficient synthetic access to the nitrogen-containing small molecules that constitute the majority of pharmaceutical agents. The need for greater efficacy, safety, and selectivity in new treatments drives increases in molecular complexity, creating urgent need for new synthetic methods to prepare the required compounds. To meet this need, this proposal aims to develop new methods to construct complex, nitrogen-rich molecules by developing new reactions of highly oxidized nitrogen compounds and supporting technologies to enable their use.

PI_NAMEs: WATSON, DONALD ALLEN (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Administrative Supplement;Automobile Driving;chemical reaction;Chemical Structure;Complex;Data;design;Development;Disease;Dose;drug synthesis;Equilibrium;experimental study;Goals;Health;Human;human disease;instrument;Manuals;manufacture;Measures;Methods;Molecular;Nitrogen;nitrogen compounds;novel;novel therapeutics;parent project;Parents;Pharmacologic Substance;Powder dose form;programs;Reaction;Reagent;Research;Research Project Grants;Robot;Safety;small molecule;Solid;Speed;Synthesis Chemistry;Technology;Work

PROJECT_TITLE: Administrative Supplement to Novel Reactions of Electrophilic Nitrogen for Preparing Bioactive Molecules


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: BOSTON

ORG_NAME: TUFTS UNIVERSITY BOSTON

ORG_STATE: MA

PHR: Narrative Obesity is a pervasive disorder linked to serious medical complications and reaching epidemic proportions in the United States. This proposal seeks to investigate the role of thrombospondin-3/a2d-1 signaling in the ventromedial hypothalamus facilitating feeding control and glucose and lipid metabolism in a body-weight independent manner. These investigations will inform new avenues for the treatment of obesity-associated metabolic disorders and mechanisms underlying metabolic dysfunction in individuals treated with gabapentinoid drugs, known to inhibit a2d-1 function.

PI_NAMEs: RIOS, MARIBEL  (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Adult;Affect;Analgesics;anti-epileptic agents;Astrocytes;Binding;blood glucose regulation;Body Weight;Brain;Brain-Derived Neurotrophic Factor;Cells;diet-induced obesity;Disease;Dyslipidemias;Eating;Electrophysiology (science);energy balance;Epidemic;Excitatory Synapse;Exhibits;Fatty Liver;feeding;gabapentin;Glucose;Glucose Intolerance;glucose metabolism;glycemic control;Health;Hepatic;Homeostasis;Human;Hyperphagia;Hypothalamic structure;improved;in vivo;Individual;Insulin Resistance;Investigation;knock-down;Link;lipid metabolism;Lipids;Maps;Mediating;medical complication;Metabolic;Metabolic Control;Metabolic Diseases;Metabolic dysfunction;Morbid Obesity;Mus;mutant;Neurons;Neurotrophic Tyrosine Kinase Receptor Type 2;novel;Obesity;obesity treatment;obesogenic;Overweight;parent grant;Pathologic;Pharmaceutical Preparations;Physiology;Play;Predisposition;pregabalin;prevent;receptor;Regulation;response;Role;Signal Transduction;Synapses;Synaptic plasticity;Synaptic Transmission;Testing;thrombospondin 3;Thrombospondins;United States;Viral

PROJECT_TITLE: Alpha2/delta1- thrombospondin-3 signaling in the central control of metabolic function

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


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

PHR: PROJECT NARRATIVE Our lab focuses on the structural and functional studies of human proteases that degrade amyloidogenic peptides, e.g. amyloid beta and insulin, peptides associated with Alzheimer disease and diabetes, respectively. We use integrative structural approaches to better understand the molecular basis of substrate recognition and regulation of human insulin degrading enzyme (IDE) and other amyloid peptide degrading enzymes such as neprilysin and angiotensin-converting enzyme. The success of our studies will allow us to selectively modulate the degradation of amyloid β and glucose regulating hormones.

PI_NAMEs: TANG, WEI-JEN  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Address;Algorithms;Alzheimer's Disease;Amyloid beta-Protein;Amyloid Fibrils;amyloid peptide;Animal Model;Blood Glucose;combat;Cryoelectron Microscopy;cytotoxic;Defect;design;Development;Diabetes Mellitus;Disease;Engineering;Enzyme Inhibitor Drugs;Enzymes;Family;Foundations;Glucagon;Glucose;Goals;Hormones;Human;image processing;improved;innovation;Insulin;Insulinase;islet amyloid polypeptide;Knowledge;Link;Mechanics;member;Metalloproteases;Methods;Modeling;Molecular;Molecular Conformation;monomer;Motion;Mus;Neprilysin;Non-Insulin-Dependent Diabetes Mellitus;novel;Peptide Hydrolases;Peptides;Peptidyl-Dipeptidase A;Physiological;Process;Proteome;Regulation;Research;Role;screening;simulation;small molecule;success;Time;time use;Work

PROJECT_TITLE: Integrative structural analysis of human insulin degrading enzyme--Revision-2

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PUBLIC HEALTH RELEVANCE (PROJECT NARRATIVE)  The proposed research is relevant to public health because it provides detailed insight into the fundamental mechanism of mitochondrial fission, an essential process in cellular homeostasis. Consequently, mitochondrial division is misregulated in several diseases, leading to organelle dysfunction and eventually cell death. Therefore, the proposed research aims dissect the regulatory mechanisms that govern organelle division and the physiologic changes associated with altered mitochondrial morphology to identify novel therapeutic targets and inform future studies that advance disease diagnosis, treatment and prevention.

PI_NAMEs: MEARS, JASON  (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: advanced disease;Apoptosis;Binding;Bioenergetics;Cardiovascular Diseases;Cell Death;Cells;combinatorial;Complex;constriction;Cryoelectron Microscopy;Cues;Defect;Degenerative Disorder;Disease;disease diagnosis;Dynamin;Evaluation;Event;experimental study;Functional disorder;Future;Guanosine Triphosphate Phosphohydrolases;Homeostasis;insight;Lipids;Liquid substance;Malignant Neoplasms;Mediating;Membrane;Metabolic stress;Methods;Mitochondria;mitochondrial membrane;Molecular;Molecular Conformation;Monitor;Morphology;Nerve Degeneration;new therapeutic target;Nucleotides;Organelles;Physiological;Prevention;Process;Production;Proteins;Public Health;public health relevance;reconstitution;recruit;Regulation;Research;response;self assembly;Shapes;Signal Transduction;Site;Stimulus;Stress;Structure;Surface;Therapeutic;therapeutic target;three dimensional structure;Time;Visualization

PROJECT_TITLE: Supplement: Defining Molecular Interactions that Drive Mitochondrial Fission


NIH_SPENDING_CATS: Infectious Diseases;Natural Products

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative  Experiments to devise new methods to synthesize cyclic peroxides will enable new approaches to prepare this family of potential drugs and explore how they are active as anti-cancer agents. Studies of the reactions involved in organic synthesis and carbohydrate chemistry will help medicinal chemists use such reactions to make biologically active compounds with greater control of three-dimensional structure. These studies are relevant to human health because they could lead to new ways of making medicines.

PI_NAMEs: WOERPEL, KEITH ALLEN (contact)

PROJECT_TERMS: Acceleration;Acetals;Address;Administrative Supplement;Antineoplastic Agents;Apoptosis;Applications Grants;Attention;Bacterial Infections;Biochemical Reaction;Biological;Biological Models;Biological Process;cancer cell;Carbamates;Carbohydrate Chemistry;Carbohydrates;Cell Death;cell killing;chemical reaction;Chemicals;Collaborations;Column Chromatography;Communication;Complication;Computer software;Computers;Cyclization;design;Disease;enantiomer;Enzyme Inhibitor Drugs;Exhibits;experimental study;Family;Funding;Goals;Grant;Health;High Pressure Liquid Chromatography;Human;Hydrogen Peroxide;innovation;instrument;Investigation;Ions;Isomerism;Kinetics;Laboratories;Literature;Malaria;Malignant Neoplasms;Medicine;Metabolic;Methods;Modernization;Molecular Conformation;National Institute of General Medical Sciences;Natural Products;NMR Spectroscopy;novel strategies;Organic Synthesis;Pathway interactions;Periodicity;Peroxides;Pharmaceutical Preparations;Phase;professor;Property;Reaction;repaired;Reproducibility of Results;Research;Resolution;Sialic Acids;Silicon Dioxide;Solvents;Structure;Study models;sugar;Synthesis Chemistry;System;Techniques;Thin Layer Chromatography;three dimensional structure;Time;Translating;Universities;Virus Diseases;Wireless Technology

PROJECT_TITLE: Stereoselective Reactions of Oxocarbenium Ions and Related Intermediates


ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative Glucocorticoids regulate genetic programs in all tissues to control inflammation, metabolism, and differentiation as a primary stress response hormone, but synthetic glucocorticoids can achieve tissue- selective effects through unknown mechanisms. The goal of this project is to understand how differences in the chemical structure of the synthetic glucocorticoids alters the shape of the receptor to differentially control stress responses across tissues, and in doing so develop glucocorticoids for treatment of colitis with improved skeletomuscular on target side-effects

PI_NAMEs: NETTLES, KENDALL W (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Acute;Antiinflammatory Effect;Binding;Biological;biological adaptation to stress;Biology;blood glucose regulation;bone;Chemical Structure;Chemicals;Chemistry;Chronic;Code;Colitis;Data;Development;Disease;Enzymes;Equipment;Fasting;feeding;Genes;Genetic;Genetic Transcription;Glucocorticoid Receptor;Glucocorticoids;glucose metabolism;Goals;Hormones;Hydrocortisone;Hyperactivity;Immune response;improved;Inflammation;Inflammatory Response;Insulin Resistance;Ligands;Link;Machine Learning;Medicine;Metabolic;Metabolism;mineralization;Modeling;Molecular;Muscular Atrophy;National Institute of General Medical Sciences;novel;Nutrient;Osteoblasts;Osteoporosis;pain reduction;Physiological;Process;programs;Proteins;receptor;response;restraint;scaffold;Shapes;side effect;Signal Transduction;Skeletal Muscle;stem cell differentiation;Stress;structural biology;Structure;Systems Biology;T cell differentiation;Techniques;Testing;Tissues;Transcriptional Regulation

PROJECT_TITLE: NIGMS Equipment Supplement for R01GM146385 TSGC


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: PHILADELPHIA

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Abnormalities in meiosis are leading causes of infertility, pregnancy loss, and birth defects (trisomy and monosomy) in humans. A number of key meiosis factors will be investigated in this project. Completion of this project will provide important insights into the etiology of infertility, birth defects, and sex chromosome anomalies.

PI_NAMEs: WANG, PEIJING JEREMY (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Biochemical;Biological;Cells;Chromosome abnormality;Chromosome Pairing;Chromosomes;Congenital Abnormality;Coupled;Defect;DNA Double Strand Break;Etiology;Eukaryota;Evolution;F Factor;Genetic;Genetic Recombination;Genetic Variation;Genome;genome integrity;Genomics;Germ Cells;Haploidy;Human;Infertility;innovation;insight;Knowledge;Maintenance;Meiosis;Meiotic Recombination;Molecular;Monosomy;novel;Organism;Play;Ploidies;Population;Pregnancy loss;prevent;Process;Proteins;Proteomics;Regulation;Role;segregation;sex;sex chromosome aneuploidy;Sex Chromosomes;Trisomy

PROJECT_TITLE: Molecular Mechanism and Regulation of Meiosis


ORG_CITY: Nashville

ORG_DEPT: BIOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: No changes being proposed.

PI_NAMEs: NORDMAN, JARED  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TITLE: Developmental control of replication initiation and genome stability


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Circadian clocks rely on precisely timed creation and destruction of clock proteins to communicate environmental signals and achieve 24-hour periodicity. We propose to understand how protein degradation impacts daily and seasonal timing mechanisms in eukaryotes.

PI_NAMEs: GENDRON, JOSHUA MARTIN (contact)

PROGRAM_OFFICER_NAME: AKACEM, LAMEESE DANA

PROJECT_TERMS: Address;Arabidopsis;Award;Biological Models;Biological Process;Biology;circadian pacemaker;Clock protein;Communication;day length;Environment;Eukaryota;Family;Feedback;Functional disorder;Funding;Future;Genetic Transcription;Goals;Hour;Human;human disease;Investigation;Laboratories;Logic;Measurement;Measures;Mediating;Molecular;Mood Disorders;National Institute of General Medical Sciences;Organism;Output;Periodicity;Photoperiod;Physiology;Plants;Prevalence;Process;protein degradation;Research;Seasons;Signal Transduction;System;ubiquitin-protein ligase;Work

PROJECT_TITLE: Protein degradation mechanisms that regulate daily and seasonal timing

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


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Martell project narrative (2-3 sentences) Technologies that enable the identification of which proteins reside in specific locations inside cells are critical for elucidating biological processes and disease states, including neurodegeneration, pathogenic infection, and cancer. One promising strategy to achieve this goal is proximity labeling (PL), but in order to enhance the sensitivity and specificity of proximal protein detection, improved PL catalysts are needed. We propose that hybrid biological-abiotic PL catalysts developed in our laboratory will enhance both sensitivity and specificity in spatially- resolved proteomic mapping, and we are employing these catalysts in neurons to benchmark their performance against existing methods and establish their broad utility as research tools.

PI_NAMEs: MARTELL, JEFFREY DANIEL (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TERMS: Amino Acids;Benchmarking;Biological;Biological Process;cancer cell;catalyst;Cells;Chemicals;Collaborations;Communities;Detection;detection sensitivity;Development;Diffusion;Directed Molecular Evolution;Disease;DNA;Electronics;Enzymes;Equipment;Exhibits;Goals;Heme;Hybrids;improved;Infection;interest;Label;Laboratories;Length;Location;Malignant Neoplasms;Mammalian Cell;Maps;Mass Spectrum Analysis;Methods;nanorod;Nerve Degeneration;Neurons;novel;novel strategies;Pathogenicity;Performance;Peroxidases;protein function;protein protein interaction;Proteins;Proteome;Proteomics;Radial;Reaction;Request for Proposals;Research;Resolution;Sensitivity and Specificity;Specificity;Structure;Surface;Synapses;synthetic construct;System;Technology;tool;Tyrosine

PROJECT_TITLE: Hybrid Biological-Abiotic Proximity Labeling Catalysts for Enhancing Spatially-Resolved Proteomics


NIH_SPENDING_CATS: Biotechnology;Infectious Diseases

ORG_CITY: WALTHAM

ORG_NAME: BRANDEIS UNIVERSITY

PHR: Project Narrative Carbohydrate binding proteins (CBPs) are a broad category of proteins involved in diverse biological processes that either guard against disease or that promote it. These proteins are involved in cancer, infectious disease, immunity, autoimmunity, diabetes, and fibrosis, to name a few. This project will develop technologies that enable rapid discovery of CBP inhibitors, which would enable us to treat disease and to untangle the complex web of CBP functions that are currently poorly understood.

PI_NAMEs: KRAUSS, ISAAC JONATHAN (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Affinity;angiogenesis;aptamer;Atherosclerosis;Autoimmunity;Avidity;Binding;Biological Process;carbohydrate binding protein;carbohydrate receptor;Categories;Cell Adhesion;Communicable Diseases;Complex;Diabetes Mellitus;Directed Molecular Evolution;Disease;Elements;Eye;Fibrosis;Goals;Heart;Immunity;Immunosuppression;in vivo;Individual;inhibitor;interest;Internet;Liver;Lung;Malignant Neoplasms;Names;nuclease;pathogen;Polysaccharides;Process;protein function;Protein-Carbohydrate Interaction;Proteins;Resistance;Rheumatoid Arthritis;RNA;Signal Transduction;Specificity;Technology;Vertebral column

PROJECT_TITLE: Technology for Directed Evolution of Glycoaptamers

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Rare Diseases

ORG_CITY: MINNEAPOLIS

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Human T-cell leukemia virus type 1 (HTLV-1) is a cancer-causing human retrovirus that infects about 15-20 million individuals worldwide. While virus particle assembly at cell-cell contacts are required for efficient virus transmission (both within and between individuals), many fundamental aspects involved in this critical mode of virus spread are poorly understood, including the nature of virus spread and particle morphology of released particles. Development of experimental workflows to enable new cutting-edge technologies will improve understanding of this distinct mode of virus transmission, which has broad relevance to other viruses capable of spread via cell-cell contacts – including transmission events

PI_NAMEs: MANSKY, LOUIS M. (contact)

PROGRAM_OFFICER_NAME: MCNEALY, TAMARA L

PROJECT_TERMS: 2019-nCoV;Address;Adult T-Cell Leukemia/Lymphoma;Behavior;Biogenesis;Biomedical Engineering;Capsid;Cell Communication;Cell Culture Techniques;Cells;Cellular biology;Cryoelectron Microscopy;Development;Disease;Electron Microscope;Electron Microscopy;Engineering;Etiology;Event;experimental study;Eye;fluorescence imaging;Fluorescence Microscopy;Goals;high resolution imaging;Human;Human Characteristics;human imaging;Human T-Cell Leukemia Viruses;Human T-lymphotropic virus 1;Image;imaging study;Imaging technology;improved;Individual;Infection;Inflammatory;insight;instrument;Knowledge;Lasers;light microscopy;live cell imaging;Malignant Neoplasms;microscopic imaging;Morphology;mutant;Nature;new technology;novel;Oral;Organ;particle;Pattern;permissiveness;Preparation;Proteins;Pulmonary Pathology;quantitative imaging;Reproducibility;Research;Resolution;Retroviridae;Role;Sampling;Skin;Spinal Cord Diseases;success;superresolution microscopy;Syndrome;Technology;Testing;Thyroid Gland;Tissues;transmission process;Tropical Spastic Paraparesis;Viral;viral transmission;Virion;virological synapse;virology;Virus;Virus Assembly;Virus Diseases;Virus Replication

PROJECT_TITLE: Imaging of HTLV-1 by cryo-CLEM

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Neurosciences;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative We propose to determine the role of sensory-evoked activity in immature adult-born olfactory sensory neurons in their survival and integration in both the healthy and the regenerating adult olfactory system. This will advance our fundamental understanding of the contribution of newborn neurons to olfactory processing and regeneration. Furthermore, our findings may suggest strategies to promote the survival and integration of transplanted stem cell-derived neurons to repair damaged brain areas.

PI_NAMEs: CHEETHAM, CLAIRE ELIZABETH JANE (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: Ablation;Adult;Affect;Area;Axon;Behavior;Biological Assay;Brain;Brain Injuries;Calcium;Chemicals;Data;Detection;Development;Effectiveness;Electron Microscopy;epithelial stem cell;Exhibits;Functional Imaging;Functional Regeneration;Genetic;Goals;Image;Immunohistochemistry;in vivo;innovation;insight;Life;Location;Mammals;Maps;Mediating;Modeling;Mus;Natural regeneration;Nervous System Disorder;neural circuit;Neurodegenerative Disorders;neurogenesis;neuron development;neuronal survival;Neurons;Newborn Infant;newborn neuron;Odorant Receptors;Odors;olfactory bulb;Olfactory Epithelium;olfactory marker protein;Olfactory Pathways;olfactory sensory neurons;optogenetics;Phase;Play;Population;Presynaptic Terminals;protein expression;Publishing;receptor expression;repaired;Research;Role;Sensory;sensory input;Signal Transduction;Stem Cell Development;stem cell population;stem cell therapy;Stem cell transplant;stem cells;structural imaging;Synapses;synaptogenesis;Testing;Time;Transcript;two-photon;Work

PROJECT_TITLE: Functional integration of newborn olfactory sensory neurons in the healthy and regenerating olfactory system

STUDY_SECTION: CSS

STUDY_SECTION_NAME: Chemosensory Systems Study Section[CSS]


ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Public Health Relevance: All life requires some form of nitrogen to function, and although the atmosphere is comprised of roughly 78% of dinitrogen (N2), it is biologically unavailable without reduction by nitrogenase enzymes, which convert unreactive N2 to a biologically-available form for uptake. The intimate details of this critical (and difficult) transformation are not understood, and although biological studies on the enzyme have demonstrated a critical role of cooperative interactions by nearby amino acid residues and a multi-metallic enzyme core, we do not know the intimate molecular details. This project aims to develop a molecular level understanding of these cooperative effects on substrate activation, which in addition to contributing important mechanistic details that govern nitrogenase function, may also translate into new catalyst development for organic and inorganic transformations.

PI_NAMEs: SZYMCZAK, NATHANIEL KOLNIK (contact)

PROJECT_TITLE: The Role of Secondary Interactions - equipment supplement

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


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Comparative Effectiveness Research;Dental, Oral, and Craniofacial Disease;Health Services;Opioid Misuse and Addiction;Opioids;Pain Research;Patient Safety;Pediatric;Prevention;Primary Health Care;Substance Misuse

PHR: High-risk medications for anesthesia, sedation and pain are frequently prescribed and administered by dentists to children and have resulted in serious unintended consequences, but unique challenges with prescribing high-risk medications to pediatric dental patients are not well understood. Understanding patterns of dental prescribing and factors associated with adverse safety outcomes can inform training models and interventions to improve evidence-based practice, ultimately decreasing risks of serious adverse events and mortality among children. Thus, this project is relevant to the NICHD high research priority to improve systems of care which can mitigate medical errors and advance child health.

PI_NAMEs: SUDA, KJ  (contact)

PROGRAM_OFFICER_NAME: ELWOOD, WILLIAM N

PROJECT_TERMS: Adolescent;Adult;Adverse event;adverse event risk;adverse outcome;Age;airway obstruction;American;Anesthesia procedures;Anti-Anxiety Agents;Attitude;Benzodiazepines;care systems;Caring;Case Study;Cessation of life;Child;Child Health;Child health care;Childhood;Chronic;Clinical;Clinical Trials;Communities;Conscious Sedation;Data;Decision Making;Dental;Dental Care;Dental Care for Children;Dental caries;Dental General Practice;Dentistry;Dentists;design;Development;Disease;Drug Prescriptions;early childhood;effectiveness testing;Emergency Care;emerging adult;Ensure;evidence base;Evidence based intervention;Evidence based practice;Exposure to;Future;General Anesthesia;General anesthetic drugs;Goals;Harm Reduction;High Prevalence;high risk;Hospitalization;human error;Hypoxemia;improved;Incidence;Infection;Inflammation;Intervention;Interview;Knowledge;Measures;Medical;Medical Care Team;Medical Errors;Medical History;medication administration;medication safety;Methods;Modeling;mortality;National Institute of Child Health and Human Development;Nurse Practitioners;Opioid;Opioid Analgesics;opioid misuse;opioid overdose;opioid use;Outcome Study;Pain;Pain management;Parents;patient safety;Patient-Focused Outcomes;Patients;Pattern;pediatric patients;Pediatrics;Perception;Pharmaceutical Preparations;Physician Assistants;Physicians;pilot test;poor health outcome;population based;practice setting;prescription opioid;Procedures;Provider;Research;Research Priority;Resources;Risk;risk perception;Risk Reduction;routine practice;Safety;safety outcomes;safety practice;Sampling;Sedation procedure;Serious Adverse Event;sociodemographic factors;Standardization;Testing;third molar extraction;Training;trend;urgent care;usability;Ventilatory Depression;wisdom tooth;Youth

PROJECT_TITLE: Pediatric Adverse Event Risk Reduction for High Risk Medications in Children and Adolescents: Improving Pediatric Patient Safety in Dental Practices


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: KINGSTON

ORG_NAME: UNIVERSITY OF RHODE ISLAND

ORG_STATE: RI

PHR: PROJECT NARRATIVE Reactive species from lipid peroxidation generated under disease conditions damage DNA and form etheno lesions, which are strongly cytotoxic, mutagenic, and carcinogenic. This project will characterize the repair of these etheno adducts by enzymes across two distinct pathways: base excision repair and direct reversal repair. Results will identify the differential repair fingerprints of such lesions and inform future translational studies that capitalize on these repair mechanisms to protect against genomic instability.

PI_NAMEs: DELANEY, SARAH ;LI, DEYU  (contact)

PROJECT_TERMS: adduct;Alkylation;base;Base Excision Repairs;cancer risk;carcinogenesis;carcinogenicity;Carcinogens;Cells;Chromatin;Chronic;chronic infection;Complex;Core Protein;cytotoxic;Data;Development;Disease;DNA;DNA Adducts;DNA Damage;DNA Packaging;DNA Repair;DNA Repair Pathway;DNA Sequence;DNA-Protein Interaction;ds-DNA;Enzymes;epigenetic marker;Equipment;experimental study;Fingerprint;Future;genome integrity;Genomic Instability;Goals;Histones;Human;improved;in vivo;Inflammation;Inflammatory;innovation;Knowledge;Lesion;Link;Lipid Peroxidation;Malignant Neoplasms;Mutation;National Institute of General Medical Sciences;Neoplastic Cell Transformation;novel;Nucleosome Core Particle;Pathway interactions;Process;programs;Proteins;repair enzyme;repaired;Reporting;Research;Research Project Grants;Techniques;Therapeutic;translational potential;translational study;Variant;Vinyl Chloride;Work

PROJECT_TITLE: NIGMS Equipment Supplement Program - 5 R01GM145790-02


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Eye Disease and Disorders of Vision;Nanotechnology;Neurosciences

ORG_CITY: RIVERSIDE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

ORG_STATE: CA

PHR: A lack of ideal optogenetic tools to investigate the physiology and pathogenesis of neurological diseases/disorders has been an impediment to the development of therapeutic interventions. The proposed research is relevant to public health by developing new technology based on acoustically activatable nanomaterials that enable the wireless modulation of neuronal functions for neuroscience research. The project speaks directly to the mission of the NIH, particularly in developing innovative technology to improve human health and well-being.

PI_NAMEs: NAM, JIN  (contact);YIN, YADONG

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Achievement;Acoustics;Address;aging population;Animal Testing;Animals;base;Biomedical Engineering;Brain;BRAIN initiative;brain tissue;candidate identification;Cardiovascular system;Cations;Cell Line;Cognitive;Colloids;Complex;Computer Models;Data;Dependence;Development;Dimensions;Disease;Dissection;effective therapy;electrical potential;Electrospinning;Encapsulated;Engineering;Exhibits;Fiber;Fluorides;Goals;Growth;Health;Human;Hybrids;Impairment;improved;In Situ;In Vitro;in vitro Model;Injectable;innovative technologies;interest;Ion Channel;Ions;Light;light emission;Longitudinal Studies;magnetic field;Metals;Methods;Mission;Morphology;Motor;nanocomposite;nanofiber;nanomaterials;nanoparticle;nanopolymer;Nanostructures;nerve stem cell;Nervous System;Nervous System Disorder;neural;neural circuit;Neurons;Neurophysiology - biologic function;neuroregulation;Neurosciences Research;new technology;novel;novel therapeutic intervention;optogenetics;particle;Pathogenesis;Pathologic;Penetration;Performance;Personal Satisfaction;Phase;Photons;Physiological;Physiology;Polymers;polyvinylidene fluoride;Prevalence;Prevention;Process;Property;Public Health;rapid growth;Research;Resolution;response;Sensory;Shapes;Signal Transduction;Site;Source;spatiotemporal;Structure;System;Technology;Testing;therapeutic development;Therapeutic Intervention;Tissues;tool;Transducers;transmission process;ultrasound;United States National Institutes of Health;vinyl fluoride;wireless;Yin;zinc sulfide

PROJECT_TITLE: Mechanoluminescent nanomaterials for optogenetic neuromodulation


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: PROJECT NARRATIVE The majority of emerging viral diseases result from the zoonotic transmission of pathogen from animals to humans. While the innate immune system plays a critical role in limiting cross-species transmissions, cellular determinants mediating this effect have yet to be fully described. This study aims to identify and characterize novel cellular factors responsible for limiting viral replication in human cells.

PI_NAMEs: POSTON, DANIEL  (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: Address;Animals;Anti-Retroviral Agents;Anti-viral Agents;Biological Assay;Biological Models;Candidate Disease Gene;Cells;Co-Immunoprecipitations;cofactor;CRISPR screen;CRISPR/Cas technology;cross-species transmission;Data;design;Emerging Communicable Diseases;Epidemic;experimental study;Future;Genes;global health;Goals;Health;HIV;HIV-2;Host Defense;Human;Human Cell Line;immunodeficiency;Individual;Infection;Infectious Agent;Innate Immune System;insight;Interferon Type I;Interferons;Life Cycle Stages;Macaca;Mediating;Methods;Monitor;Natural Immunity;nonhuman primate;novel;pathogen;pathogenic virus;Play;Primate Lentiviruses;Primate Retrovirus;Production;Proteins;Publishing;Resistance;Role;screening;Screening procedure;SIV;System;tool;transmission process;TRIM5 gene;Tropism;Viral;Viral Physiology;Viral Proteins;viral transmission;Virus;Virus Diseases;Virus Replication;Work;Zoonoses

PROJECT_TITLE: Elucidating antiviral defenses against diverse immunodeficiency viruses using a novel, high-throughput CRISPR/Cas9 screening method.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F17-P(20)L]


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative This administrative supplement to the parent grant will support the career of Amanda McArthur, PhD, who comes from a background underrepresented in science. Further, the project Dr. McArthur undertakes will provide data about how stigmatizing documentation relates to observed interpersonal processes and patient experience of care. The project proposed here could provide compelling evidence of the need for change in the ways we document about patients.

PI_NAMEs: BEACH, MARY CATHERINE  (contact)

PROGRAM_OFFICER_NAME: OLADEINDE, YEWANDE A

PROJECT_TERMS: Administrative Supplement;Affect;Age;Agreement;Algorithms;Area;Attention;Attitude;Behavior;Bypass;Canis familiaris;career;Caring;Categories;Clinical;Communication Methods;Computerized Patient Records;Consensus;Data;Disparity;disparity reduction;Doctor of Philosophy;Documentation;Drug Prescriptions;Education;Equity;ethnic identity;experience;Feedback;Focus Groups;Gender;Goals;health care quality;health literacy;Health Professional;Health system;Healthcare;Healthcare Systems;Impaired health;implementation science;implicit bias;improved;Individual;individual patient;Judgment;Language;low health literacy;Measures;Medical;Medical Records;medical specialties;Natural Language Processing;Obesity;older adult;oral communication;parent grant;Pathway interactions;patient-clinician communication;Patients;Pattern;Persons;Physicians;pilot test;Politics;Process;Punishment;Quality of Care;Race;racial disparity;Reading;Records;Role;Science;sex;Sickle Cell Anemia;Social Class;Social status;Speech;Stereotyping;Stigmatization;substance abuser;Substance Use Disorder;Taxonomy;Testing;transmission process;Work;Writing

PROJECT_TITLE: Association of Stigmatizing EHR Language with Clinician-Patient Communication and Patient Experience


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

ORG_STATE: PA

PHR: Project Narrative Trauma and surgical sepsis frequently lead to death and/or persistent critical illness, however there are no targeted therapies to improve outcomes. With advances in technologies, we can now measure changes in gene and protein expression in thousands of cells at the single cell level and at the same time measure levels of thousands of biomolecules in the circulation. We will continue to apply these technologies to the study of trauma and sepsis to identify predictive biomarkers and identify novel therapeutic targets.

PI_NAMEs: BILLIAR, TIMOTHY R (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acidosis;Acute;Age;Animal Model;Anticoagulants;Apoptosis;Atlases;Automobile Driving;Award;biomarker identification;Blood;Blood specimen;Breeding;Cardiac;Cardiac Myocytes;Cell Death;Cell Lineage;cell type;Cells;Cessation of life;Chromatin;Circulation;Citrates;Coagulation Process;Comparative Study;Complex;Contract Services;cost;Creativeness;Critical Illness;Cytolysis;Data;Data Set;derepression;Development;Endothelial Cells;Epigenetic Process;Equipment;equipment acquisition;equipment training;Female;Functional disorder;Funding;Funding Agency;Future;Gene Expression;Hand;Hematology;Hemorrhage;Hemorrhagic Shock;Heparin;Hepatocyte;Hour;Human;Immune;Immune System Diseases;Immunosuppression;improved outcome;indexing;Injury;insight;instrument;Intensive Care;Laboratories;Laboratory Research;Lead;Lipids;Liquid substance;Maintenance;male;Manuals;Measures;Medicine;Megakaryocytes;member;metabolomics;Modeling;Morbidity - disease rate;mortality;mouse model;multidimensional data;multiple omics;Mus;Myeloid Cells;Nature;new therapeutic target;novel;online resource;Operative Surgical Procedures;Organ;Outcome;Parents;Pathway interactions;patient stratification;Patients;Pattern;Peripheral Blood Mononuclear Cell;Phenotype;Plasma;Polycomb;predictive marker;Predisposition;Process;programs;protein expression;Proteins;Proteomics;Publishing;Puncture procedure;Recurrence;Research;Resources;response;response to injury;Resuscitation;Role;secondary infection;Secondary to;Sepsis;severe injury;sex;single cell genomics;Standard Model;Study models;surgical research;systemic inflammatory response;targeted treatment;Technology;Temperature;therapeutic target;Time;Training;Translating;Trauma;trauma induced coagulopathy;Trauma patient;treatment group;Tube;Work

PROJECT_TITLE: Mechanisms of Immune Dysfunction after Trauma and Surgical Sepsis


NIH_SPENDING_CATS: Genetics

ORG_CITY: DURHAM

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Relevance: Mammalian cells use biological zip codes to transport mRNAs, which encode the information for the synthesis of proteins, to specific locations in the cell, so that proteins are made in their appropriate location. This RNA localization process is critical to early development, learning and memory, and at the level of the individual cell, to the secretion of hormones and neurotransmitters as well the cell surface localization of proteins functioning in signaling and cell-cell communication. The findings from this study are expected to reveal new mechanisms of RNA localization and identify conserved pathways that may be dysregulated in diseases of development, metabolism, and ageing.

PI_NAMEs: NICCHITTA, CHRISTOPHER V. (contact)

PROJECT_TERMS: Address;Aging;Binding;Binding Proteins;Biochemical;Biogenesis;Biological;Biology;Cell Communication;Cell Culture System;Cell surface;Cells;crosslinking and immunoprecipitation sequencing;Development;Disease;Endoplasmic Reticulum;Gene Expression;Genes;Hormone secretion;in vivo evaluation;Individual;insight;Laboratories;Learning;Location;Mammalian Cell;Mediating;Membrane Proteins;Memory;Messenger RNA;Metabolism;Modeling;Neurotransmitters;Pathway interactions;Peptide Signal Sequences;posttranscriptional;Process;Protein Biosynthesis;protein function;Protein translocation;Proteins;Proteome;proteostasis;Regulation;Research;ribophorin I;ribosome profiling;Ribosomes;RNA;RNA-Binding Proteins;Role;secretory protein;Signal Recognition Particle;signal sequence receptor;Signal Transduction;Site;System;Testing;tissue/cell culture;trafficking;Transcript;transcriptome;transcriptome sequencing;Translation Initiation;Translational Regulation;Translations

PROJECT_TITLE: Mechanisms of RNA localization and translational regulation on the endoplasmic reticulum


NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE  Wnt signaling is a rapidly evolving and important field of investigation and new regulators involved in this cascade are continuously being identified. Our study focuses on developing a mechanistic understanding of PTPRF-mediated regulation of Wnt signaling and intestinal stem cell function. Results from our studies will help identify new therapeutic strategies for treating Wnt-driven diseases by using PTPRF as a target.

PI_NAMEs: GAO, TIANYAN  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: 3-Dimensional;Attention;Attenuated;Automobile Driving;beta catenin;Bioinformatics;Biological Process;cancer cell;Caveolins;Cell Differentiation process;Cell membrane;Cell Proliferation;Cells;Cellular biology;Colon;colon cancer patients;Colon Carcinoma;colon tumorigenesis;Colorectal Cancer;Complex;CRISPR/Cas technology;Data;Development;Disease;Endocytosis;Ensure;Epithelium;Equilibrium;Genes;Goals;Human;Human body;In Vitro;in vivo;inhibitor;insight;Internal Ribosome Entry Site;intestinal crypt;intestinal epithelium;intestinal homeostasis;Intestines;Investigation;knock-down;Knock-out;Knockout Mice;Knowledge;LGR5 gene;Maintenance;Mediating;Modeling;Molecular;Mus;Mutation;novel;novel therapeutic intervention;Oncogenic;Organism;Organoids;Pathway interactions;Phosphoric Monoester Hydrolases;Phosphorylation;Physiological;Physiology;Play;Process;Proliferating;Protein Dephosphorylation;Protein Kinase;Protein phosphatase;Protein Tyrosine Phosphatase;Proteins;PTPRR gene;receptor;Regulation;Reporter;Role;Sampling;self-renewal;Signal Transduction;single-cell RNA sequencing;stem cell fate;stem cell function;stem cell proliferation;stem cells;success;System;targeted treatment;Technology;Testing;Tissues;tumor growth;ubiquitin-protein ligase;Ubiquitination;Villus;WNT Signaling Pathway

PROJECT_TITLE: Study of PTPRF-Mediated Regulation of Wnt Signaling- Supplement


NIH_SPENDING_CATS: Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_STATE: MI

PHR: Molecular mechanisms of intersecting human telomeric functions Narrative Telomeres are structures found at the ends of our chromosomes that are instrumental in ensuring the integrity of our genomes. This proposal aims to understand at a molecular level how human telomeres help maintain chromosome ends in different biological contexts, including in cancer cells, stem cells, and cells undergoing meiosis. These studies will enhance our knowledge of how telomeres uphold genome integrity and help develop strategies to counter telomere dysregulation in human diseases like cancer and infertility.

PI_NAMEs: NANDAKUMAR, JAYAKRISHNAN  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Binding;Biochemical;Biochemistry;Biological;cancer cell;Cell Proliferation;Cells;Cellular biology;Chromosomes;Complex;Crystallography;Cytoskeleton;Disease;DNA;DNA Damage;Ensure;Enzymes;Functional disorder;Genetic Crossing Over;Genome;genome integrity;Germ Cells;Human;human disease;Infertility;Knowledge;Malignant Neoplasms;Meiosis;Molecular;novel therapeutic intervention;novel therapeutics;Nuclear Envelope;Pathway interactions;Process;Production;protein complex;Proteins;recruit;Ribonucleoproteins;RNA;S phase;Somatic Cell;stem cells;Structure;Telomerase;telomere;Telomere Recombination;Testing;Therapeutic;therapeutic development


ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE: Vimentin intermediate filaments are a key regulator of mammalian cell shape, mechanical integrity, and motility, but remain poorly understood for groups of cells embedded within 3D extracellular matrix. Here, we investigate the role of vimentin in cellular deformability, matrix adhesion, and multicellular coordination during directed migration. These fundamental studies will enable new insights into the structure and function of vimentin during physiological processes, as well as its dysregulation in pathologic states.

PI_NAMEs: GUO, MING  (contact);WONG, IAN Y

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: 3-Dimensional;Address;Adhesions;Affect;Cancer Model;Cell Communication;cell motility;Cell Shape;Cell-Cell Adhesion;Cells;Cytoskeleton;Development;Disease;Epithelial Cells;Epithelium;Exhibits;Extracellular Matrix;Genetically Engineered Mouse;Goals;Impairment;In Vitro;in vivo regeneration;insight;Intermediate Filaments;Keratin;Knock-out;Mammalian Cell;mammary gland development;Measurement;Mechanics;Mesenchymal;migration;Molecular Biology;Morphology;mosaic;Motility;Mus;Organ;Pathologic;Physiological;Physiological Processes;Play;repaired;Research Personnel;Role;spheroids;Structure;Technology;tissue repair;Tissues;Traction;tumor progression;Vimentin;Work;wound

PROJECT_TITLE: Mechanobiology of Vimentin Intermediate Filaments in 3D Collective Cell Migration


NIH_SPENDING_CATS: Patient Safety;Prevention

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Unanticipated adverse drug reactions remain a major cause for restricted access to new medications and post marketing withdrawals of new drugs. Adverse drug reactions are often caused by reactive metabolic species that form covalent adducts with proteins but the identitiy and extent of protein adducts formed is often difficult to predict or prevent. This project will establish novel proteomics tools that can be used to evaluate mechanisms of adverse drug reactions and that can be incorporated into drug development workflows for early identification of drug protein adducts.

PI_NAMEs: ISOHERRANEN, NINA  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: access restrictions;adduct;adverse drug reaction;Adverse event;Biological;Biological Markers;Catalogs;Characteristics;Chemicals;Clinical;Complex;Data;Development;drug development;drug discovery;drug withdrawal;Early identification;enzyme mechanism;Enzymes;Exposure to;Genotype;Goals;Hepatocyte;high dimensionality;Human;In Situ;In Vitro;Individual;innovation;insight;inter-individual variation;Liver;Liver Microsomes;Mass Spectrum Analysis;medication safety;Metabolic;Methods;Modeling;Modification;novel;novel therapeutics;Patients;Pharmaceutical Preparations;post-market;Post-Translational Protein Processing;Preparation;prevent;Protein Secretion;Proteins;Proteome;Proteomics;rapid technique;Recombinants;Research;risk mitigation;Safety;safety assessment;System;targeted treatment;Testing;therapy design;tool;Withdrawal;Work;Xenobiotics

PROJECT_TITLE: Identification and quantification of drug-protein adducts by mass spectrometry

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(02)]


NIH_SPENDING_CATS: Contraception/Reproduction;Genetics

ORG_CITY: WORCESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Project Narrative Argonaute proteins in animals, plants, fungi, and bacteria use small pieces of RNA or DNA to find and control genes. Studying how Argonautes work has already led to small RNA drugs to turn off fatal human disease genes. The proposed research will reveal how organisms make small RNAs and use Argonautes to control development and reproductive health.

PI_NAMEs: ZAMORE, PHILLIP D (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Animals;Bacteria;Bacterial Genome;Biochemical;Biochemistry;Biology;Chromosomes;Compensation;Complex;computer studies;design;Development;Dicer Enzyme;DNA;DNA biosynthesis;DNA Sequence;DNA Topoisomerase IV;Ensure;Evolution;Exclusion;experimental study;fly;fungus;Gene Expression;Genes;Genetic;Genetic Transcription;Genomic Segment;Germ Cells;Goals;Guide RNA;human disease;improved;in vivo;insight;Male Infertility;Mediating;MicroRNAs;Molecular;Moths;mouse genetics;mRNA Stability;Mus;Mutation;Organism;Pathway interactions;Pharmaceutical Preparations;piRNA;placental mammal;Plants;pre-miRNA;Process;Protein Family;Proteins;Reproductive Health;Research;Ribosomes;RNA;RNA Precursors;RNA Sequences;Role;Small RNA;Specificity;sperm cell;Spermatocytes;Thermus thermophilus;Transcript;Translations;Work

PROJECT_TITLE: Understanding the Evolution, Biology, and Molecular Mechanism of Argonaute


ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

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: Body Size;Bone Morphogenetic Proteins;Caenorhabditis elegans;Cardiovascular Diseases;Computer software;Defect;Development;Disease;Fluorescence;Funding;imaging software;improved;in vivo;insight;Malignant Neoplasms;Measurement;Molecular;Musculoskeletal Diseases;Mutation;Output;Pathway interactions;Play;Process;Productivity;Proteins;Research;Role;Signal Pathway;Signaling Protein;therapeutic target

PROJECT_TITLE: Molecular mechanisms regulating and interpreting BMP signaling


NIH_SPENDING_CATS: Rehabilitation

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: Project Narrative This program targets molecular scale prosthetics to replace missing proteins that underlie a range of currently incurable human diseases and a general and automated platform for making these and many other types of natural product-based therapeutics. Collectively, these efforts stand to unleash the substantial untapped potential for naturally occurring small molecules to better human health.

PI_NAMEs: BURKE, MARTIN D (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Chemistry;Molecular;Prosthesis

PROJECT_TITLE: Molecular Prosthetics and Lego Chemistry


NIH_SPENDING_CATS: Neurosciences

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE The goal of our laboratory is to understand the mechanisms of action of volatile anesthetics (VAs) in order to optimize clinical care and understand control of consciousness. We discovered that VAs inhibit mitochondrial function, producing specific defects in excitatory neurotransmission. We are extending the studies of VAs and mitochondria to understand arousal from the anesthetic state, and how VAs produce undesired long-term effects.

PI_NAMEs: MORGAN, PHILIP G (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Acute;Administrative Supplement;Anesthetics;Animals;Arousal;Calcium;Cells;cholinergic neuron;clinical care;Complex;Conscious;Data;Defect;Electron Transport;Endocytosis;Endoplasmic Reticulum;Equipment;Exposure to;Failure;genetic approach;Glutamates;Goals;Hand;Human;Isoflurane;Laboratories;Link;Long-Term Effects;Metabolism;Mitochondria;Modern Medicine;Molecular Mechanisms of Action;Mus;Neurons;neurotransmission;Phylogenetic Analysis;Production;reuptake;Synapses;synaptic inhibition;Testing;Unconscious State;Volatilization;Work

PROJECT_TITLE: Volatile Anesthetics and Metabolism Administrative Supplement for Equipment


ORG_CITY: IRVINE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: The supplement instructions PA-20-272 state: “At a minimum, the Research Strategy section should be completed and must include a summary or abstract of the funded parent award or project. Other sections should also be included if they are being changed by the proposed supplement activities.” The original Project Narrative has not changed as a result of the proposed supplement activities.

PI_NAMEs: HUANG, LAN  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Funding;multicatalytic endopeptidase complex;parent project;Proteomics;Research;supplemental instruction;System;Technology;Ubiquitin

PROJECT_TITLE: Supplement: Advancing Proteomics Technologies to Decipher the Ubiquitin-Proteasome System

STUDY_SECTION: MRAB

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


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: PROJECT NARRATIVE P. aeruginosa is a principal pathogen in cystic fibrosis and hospital-acquired infections; its pathogenicity is linked to biofilm formation. Here we aim to further the research of our current RO1 and deeper characterize a pathway for biofilm regulation in P. aeruginosa. The proposed research is relevant to public health because the discovery of new pathways that regulate biofilm growth will provide new targets for preventive and therapeutic interventions. Thus, the proposed research is relevant to the part of the NIH’s mission that pertains to developing fundamental knowledge that will extend healthy life and reduce the burdens of illness.

PI_NAMEs: BOON, ELIZABETH M (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: acute infection;Antibiotic Resistance;Antibiotics;Bacteria;Binding;Biochemical;Biochemical Process;Biological Assay;burden of illness;Chronic;chronic infection;Clinical;Cystic Fibrosis;denitrification;Development;experience;Failure;Family;Feedback;forging;Funding;Goals;Growth;Hemeproteins;human pathogen;Infection Control;infectious disease treatment;innovation;Intervention;Knowledge;Laboratories;Life;Link;member;Microbial Biofilms;Mission;Molecular;Motility;Nitric Oxide;Nosocomial Infections;novel;novel therapeutics;Organism;pathogen;Pathogenicity;Pathway interactions;Periodicity;Phenotype;Phosphotransferases;preventive intervention;protein-histidine kinase;Proteins;Pseudomonas aeruginosa;Public Health;quorum sensing;Regulation;Research;Respiration;Risk;Role;sensor;Signal Pathway;Signal Transduction;Testing;Therapeutic;Therapeutic Intervention;United States National Institutes of Health;Virulence;Work

PROJECT_TITLE: The role of NosP in Pseudomonas aeruginosa biofilm development


ORG_CITY: Newark

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Cellular stress response is a common pathway for cells to respond to daily stress. It is dysregulated in many human diseases accompanied by disrupted daily rhythms. Understanding its interactions with the body clock is therefore fundamentally important for understanding general principles of biological systems and for treating these diseases using its FDA-approved modulators.

PI_NAMEs: CAO, RUIFENG (RAY)  (contact)

PROJECT_TERMS: Address;Behavioral;biological adaptation to stress;Biological Clocks;Biological Process;biological systems;Brain Diseases;Cell Physiology;Cells;Cellular Stress;circadian;circadian pacemaker;Circadian Rhythms;Complex;Couples;Data;Disease;Endoplasmic Reticulum;Eukaryotic Initiation Factors;FDA approved;Functional disorder;Gene Proteins;Genes;Health;Homeostasis;Human;human disease;imprint;inhibitor;innovation;Link;Metabolism;Molecular;mouse genetics;mouse model;Neuronal Differentiation;Neurons;novel;Pathway interactions;Patients;Pharmaceutical Preparations;Phosphotransferases;Physiology;Prokaryotic Initiation Factor-2;Property;protein kinase R;Proteins;Publishing;response;Role;Signal Transduction;Stress;stressor;Testing;Time;tissue regeneration;tool;Work

PROJECT_TITLE: Integrated stress response and the circadian clock

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR]


NIH_SPENDING_CATS: Nutrition;Pediatric;Rare Diseases

ORG_CITY: College Station

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

ORG_STATE: TX

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)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Active Sites;Address;Adjuvant;Aerobic;Autophagocytosis;Back;Binding;Biological Models;Biology;Bypass;cell growth;Cell membrane;Cell Physiology;Cell Respiration;Cells;Child;Childhood;Coenzymes;cofactor;Complex;Copper;Cysteine;cytochrome c oxidase;Cytosol;Development;Disease;disease-causing mutation;Disulfides;Drug Transport;Eating;Enzymes;Eukaryota;Family;FDA approved;Food Energy;Funding;gene discovery;Generations;Genetic;Genetic Models;genome-wide;Genomics;Goals;Golgi Apparatus;Growth and Development function;Health;Homeostasis;Human;human disease;hypocupremia;improved;infancy;Infant;Inner mitochondrial membrane;innovation;interdisciplinary approach;Investigation;Ionophores;Knowledge;Ligands;Medicine;Membrane;Menkes Kinky Hair Syndrome;Metabolic Pathway;Micronutrients;Mitochondria;Mitochondrial Diseases;Mitochondrial Matrix;mitochondrial metabolism;model organism;Molecular;mouse model;Mutation;National Institute of General Medical Sciences;neuropathology;novel;Organism;Oxidoreductase;Pathway interactions;Perinatal mortality demographics;Pharmaceutical Preparations;Play;programs;Proliferating;Property;Proteins;Proteomics;PTGS1 gene;PTGS2 gene;Research;respiratory enzyme;restoration;Role;Saccharomyces cerevisiae;Safety;Signal Transduction;small molecule;Spanish;Structure;success;superoxide dismutase 1;Therapeutic;therapeutic development;Trace metal;trafficking;Translating;treatment strategy;Work;Yeast Model System;Yeasts;Zebrafish

PROJECT_TITLE: Mitochondrial Copper Biology


NIH_SPENDING_CATS: Natural Products

PHR: Project Narrative  This program is discovering catalytic reactions that selectively perform the atomistic change of C(sp3)–H to C–O, C–N, and C–C in complex molecules, which has been demonstrated to alter their biological function and efficacy as therapeutics. Using these reactions, we are pioneering the area of late-stage functionalization where atomistic changes are made directly on drugs and natural products, circumventing lengthy, individual de novo syntheses, which present a significant technological challenge to drug discovery. To broaden the application of late-stage functionalization, we are inventing catalysts that have a higher tolerance for pre-existing reactive functionality and effect novel site-selectivity; control over three-dimensional outcomes; and C(sp3)–H cross- couplings with O- , N- , and C-containing complex fragments.

PI_NAMEs: WHITE, MARIA CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Selective C(sp3)-H Oxidations and Functionalizations with Tunable Metal Catalysts for Synthesis


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Project Narrative Successful completion of development requires tight control of gene expression. The research described in this proposal will examine the basic mechanisms that determine where and when the DNA regulatory elements controlling gene expression are used. Defects in gene regulation can endow cells with new properties that lead to disease; therefore, knowledge of the underlying mechanisms is important for human health.

PI_NAMEs: MCKAY, DANIEL J (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: 3-Dimensional;Adopted;Animal Model;Animals;Binding;Cell Differentiation process;Cells;Chromatin;Decision Making;Defect;Development;Developmental Gene;Disease;DNA;DNA Binding;DNA Sequence;Drosophila genus;Endowment;Enhancers;Epigenetic Process;Equipment;Gatekeeping;Gene Activation;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic information;genetic resource;Genetic Transcription;Genome;Genotype;Grant;Health;histone modification;Histones;Human;Knowledge;Maintenance;Multipotent Stem Cells;mutant;Nucleosomes;Play;Post-Translational Protein Processing;prevent;Process;Property;Proteins;Regulatory Element;Research;Role;Switch Genes;Testing;Time;transcription factor;Transcriptional Regulation

PROJECT_TITLE: Genetic and epigenetic mechanisms of developmental gene regulation


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

ORG_STATE: MA

PHR: PROJECT NARRATIVE Gene expression plays a central role in immune regulation and is often affected in immune diseases and during viral infections. The goal of the proposed research is to determine the rules governing the regulation of immune genes and to determine the mechanisms by which viruses hijack immune expression programs to favor viral replication. The findings and principles uncovered by these studies will lay a foundation for the design of novel therapeutic strategies.

PI_NAMEs: FUXMAN BASS, JUAN IGNACIO (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Affect;Binding;Biological;Biological Assay;Biological Process;Cell Proliferation;cell type;Cells;Cues;cytokine;Cytokine Gene;Data Set;design;Disease;DNA Viruses;Double Stranded DNA Virus;Foundations;Gene Expression;Gene Expression Profile;gene regulatory network;Genes;genetic manipulation;Genetic Transcription;Genome;genome-wide;Goals;Human;Hybrids;Immune;Immune Evasion;immune function;Immune response;Immune System Diseases;immunoregulation;Immunosuppression;Individual;Laboratories;Logic;Metabolic;Modeling;novel;novel therapeutic intervention;Outcome;pathogen;Play;Productivity;programs;Promoter Regions;protein protein interaction;Regulation;Regulatory Element;Reporter;Research;response;Retroviridae;Role;Specificity;Structure;Therapeutic;transcription factor;Transcriptional Regulation;Viral;Viral Genes;Viral Genome;Viral Physiology;Virus;Virus Diseases;Virus Latency;Virus Replication;Yeasts

PROJECT_TITLE: Structure and Function of Immune Gene Regulatory Networks


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: RESEARCH STRATEGY 1) The parental grant abstract (R35GM136379)  Fungal pathogens infect humans, animals, and plants and cause severe consequences on global human health and crop production. Communication between hosts and pathogens is essential for host defense and pathogen virulence, but the underlying mechanisms are not well understood. Previous studies in my lab discovered that some non-coding regulatory small RNAs (sRNAs) from fungal pathogens, such as Botrytis cinerea, which causes grey mold disease on more than 1000 plant species, can be transported into host plant cells and suppress host immunity genes, a mechanism called “Cross-Kingdom RNAi”. Recently, we discovered that such sRNA communication is bi-directional. Plant hosts have also developed the ability to deliver sRNAs, mainly using extracellular vesicles, to fungal cells and induce cross-kingdom RNAi of fungal virulence-related genes. Such sRNA communication was also observed between mammals and parasites. Despite more studies across diverse systems demonstrating that mobile sRNAs are key regulatory molecules in host and pathogen interactions, the field of cross-kingdom/cross-species RNA communication is still in its infancy. This proposal is designed for the use of the plant Arabidopsis and the fungal pathogen Botrytis as a model system to address the outstanding questions in this field. These questions include how host cells control sRNA transport upon infection, how specific classes of small RNAs are sorted into extracellular vesicles, how fungal cells deliver sRNAs into host cells, what are the mechanisms of RNA and vesicle uptake in the host cells and fungal cells, and whether other classes of RNAs such as mRNAs and long non-coding RNAs associate with extracellular vesicles and move between host and fungal cells as well as how they function in the counter party, etc.. A combination of genetics, genomics, biochemical and molecular biology approaches will be used. This project is expected to provide unprecedented insight into the underlying mechanisms of cross-kingdom/cross- species RNA communications, which will ultimately help develop innovative and eco- friendly disease control strategies such as RNA-based fungicides or antifungal drugs. 2) Scientific justification Request for a Blizzard NU-99828JG -86°C Ultralow Freezer The PI requests fund to purchase a Blizzard NU-99828JG -86°C Ultralow Freezer (with necessary racks) from NuAire, Inc., which will replace our 20-year-old broken -80C freezer. The old -80C freezer was unstable for the last two years, and the temperature could only go down to -50 to -40C. It was completely broken recently, which caused serious problems for the research in the lab. This instrument is essential for this project and for a molecular biology lab. It will enable us to store all the plant leaves and cultured fungal and bacterial samples, extracellular vesicles isolated from plants, fungi and bacteria, isolated small RNAs and mRNAs, all the bacterial and fungal strains etc..

PI_NAMEs: JIN, HAILING  (contact)

PROJECT_TERMS: 20 year old;Address;Animals;anti-fungal agents;Arabidopsis;Bacteria;Biochemical;Biochemistry;Biological Models;Botrytis;Cells;Cellular biology;Communication;design;Disease;disorder control;extracellular vesicles;Friends;Funding;fungicide;fungus;Genes;Genetic;Genomics;Grant;Health;Host Defense;Human;Immunity;infancy;Infection;innovation;insight;instrument;Mammals;Messenger RNA;Molds;Molecular Biology;Parasites;pathogen;pathogenic fungus;Plant Leaves;Plants;Production;Research;RNA;RNA Interference;RNA Transport;Sampling;Small RNA;Sorting;System;Temperature;Untranslated RNA;uptake;Vesicle;Virulence

PROJECT_TITLE: Cross-kingdom RNA communications between plant and fungal pathogens