ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

ORG_STATE: CO

PHR: Recent years have seen significant advances using targeted and immunotherapies for melanoma, but most patients remain at high risk for recurrence and metastases necessitating the need for more effective therapies. US veterans between ages 55-59, 50-54, and 45-49 are 450%, 17%, and 6% more likely to develop melanoma than the general US population. The survival rate of patients with advanced melanoma at 5 years is less than 5%. Recurrent and/metastatic melanoma is notoriously resistant to all existing forms of cancer therapies. We discovered that a protein named IL-1 receptor associated kinase-M (IRAK-M) is deficient in melanoma but plays a central role in 1) the ability for cancer cells to metastasize and 2) shutting down antitumor immune responses. We will test the novel idea that restoring IRAK-M in melanoma cells, by repurposing already FDA-approved compounds, will prevent metastases and reinstate tumor immunity.

PI_NAMEs: DAVILA, EDUARDO V (contact)

PROJECT_TERMS: Acceleration;Accounting;Adenosine;ADORA2A gene;Age;anti-tumor immune response;cancer cell;Cancer Etiology;cancer immunotherapy;cancer therapy;cancer type;Cell Line;Cell Mobility;cell motility;Cells;Cellular Morphology;Cessation of life;Chronic;Clinical;clinically relevant;Cytoplasm;Cytoskeleton;Data;Development;Disseminated Malignant Neoplasm;Distal;effective therapy;Endothelial Cells;Engineering;exhaustion;Exhibits;experience;extracellular;Family;Family member;FDA approved;Functional disorder;Gene Chips;Generations;Genes;Genetic;genetic approach;Genetic Transcription;Goals;high risk;Homeobox;Human;Immunity;Immunotherapy;Impairment;In Vitro;in vivo;Inflammatory;insight;Integrins;Interleukin-1;Interleukin-1 beta;interleukin-1 receptor-associated kinase;Interleukin-1 Receptors;Interruption;Invaded;IRAK1 gene;ITGA11 gene;knock-down;Link;Malignant Neoplasms;Mediating;Medical;Melanoma;Melanoma Cell;member;Metastatic Melanoma;metastatic process;Metastatic to;Metastatic/Recurrent;Modeling;Molecular;Morbidity - disease rate;Morphogenesis;mortality;Mus;Myeloid-derived suppressor cells;Names;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;novel therapeutic intervention;overexpression;Pathway interactions;Patients;Pharmaceutical Preparations;Phosphotransferases;Platelet-Derived Growth Factor;Play;Population;Pre-Clinical Model;prevent;Process;Production;Property;Proteins;receptor;Recurrence;Regulation;Reporting;Repression;Resistance;Role;Sampling;Signal Pathway;Signal Transduction;standard of care;success;Survival Rate;T cell response;T cell therapy;T-Lymphocyte;Testing;Therapeutic;Toll-like receptors;tumor;tumor growth;Tumor Immunity;tumor microenvironment;tumor progression;Vascular Endothelial Growth Factors;Veterans

PROJECT_TITLE: Restoring the Regulation of a Central Signaling Pathway to Prevent Metastases and Reinstate Tumor Immunity


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: BALTIMORE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: Patients with critical surgical disorders such as trauma, thermal injury, shock, sepsis, and massive surgical operations are commonly complicated with gut mucosal injury and bleeding, but effective therapies to preserve epithelial integrity are limited to date. Delayed mucosal repair causes disruption of mucosal epithelial integrity, thus contributing to morbidity and mortality. Although mucosal healing after acute injury is crucial for maintaining epithelial integrity during critical surgical stress, the exact mechanism underlying this process remains unclear. The immediate goal of this study is to define the cellular and molecular mechanisms underlying intestinal epithelium homeostasis under critical surgical conditions. We will test the possibility that an important protein α4 controls gut mucosal homeostasis by altering given noncoding RNAs. Completion of these experiments will create a fundamental basis for development of novel therapies to preserve epithelial integrity in our VA patients.

PI_NAMEs: WANG, JIAN-YING  (contact)

PROJECT_TERMS: Acute;Affect;Aging;Anabolism;antagonist;Apoptosis;Bacteria;Binding Proteins;Blood;Burn injury;Cause of Death;Caveolins;cell motility;Cell Physiology;cell type;chromatin remodeling;cIAP1 protein;Critical Illness;Development;Disease;effective therapy;Epithelial Cells;epithelial repair;Epithelium;Exhibits;experimental study;Functional disorder;Funding;gastrointestinal epithelium;Gene Expression;gene repression;Genes;Genetic Transcription;Goals;Gut Mucosa;H19 gene;healing;heat injury;Hemorrhage;Homeostasis;human disease;HuR protein;IGF2 gene;Impairment;Inflammation;Injury;intestinal epithelium;intestinal homeostasis;intestinal maturation;Intestinal Mucosa;Intestines;Link;Maintenance;Messenger RNA;MicroRNAs;migration;Mission;Molecular;Morbidity - disease rate;mortality;mRNA Stability;Mucous Membrane;Multiple Organ Failure;Mus;Natural regeneration;novel;novel therapeutics;Nucleotides;operation;Operative Surgical Procedures;Pathway interactions;Patients;Pattern;Permeability;Play;Polyamines;Population;posttranscriptional;preservation;prevent;Process;programs;protein metabolism;Protein phosphatase;Proteins;receptor;repaired;Repression;response;restoration;RNA;RNA-Binding Proteins;Role;Sepsis;Shock;STIM1 gene;Stream;Stress;Testing;Tissues;Toxin;Transcription Process;Transfection;Translational Repression;Trauma;Traumatic injury;Untranslated RNA;wound;Wounded area

PROJECT_TITLE: Surgical Studies on Mucosal Homeostasis


ADMINISTERING_IC: MH

ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Mental Health;Neurosciences

ORG_CITY: RICHMOND

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE Functioning in a social group is fundamental to the human experience and is critical to the health of both the individual and society. Here, to illuminate the molecular origin of complex social behaviors, I will study a novel transcription factor whose expression in prefrontal cortex was previously determined to protect against stress- induced social deficits in laboratory rodents. I will use novel synthetic transcription factor variants, virally delivered to the prefrontal cortex of mice, and combined with behavior and transcriptomic analyses to evaluate the causal role of this transcription factor in regulating gene expression and complex social behaviors.

PI_NAMEs: TRUBY, NATALIE L (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Ablation;adaptive immune response;Agreement;Animals;Area;autism spectrum disorder;awake;Behavior;Behavioral;Behavioral Assay;Binding Proteins;Bioinformatics;Biological;Brain;career;Cartoons;Chronic;Classification;Cognition;Complex;Data;Data Set;Disease;DNA;DNA Sequence;DNA Transposable Elements;Elements;Enhancers;Event;Evolution;experience;Fellowship;Functional disorder;Gene Expression;gene product;Gene Targeting;Genes;Genetic Transcription;Genomics;Goals;Health;hippocampal pyramidal neuron;Human;Immune;Immune response;Immune signaling;in vivo;Individual;Influentials;innovation;Interferons;Intervention;Knowledge;Laboratories;Learning;Link;Literature;Maintenance;Major Depressive Disorder;Medial;Mediating;Mental disorders;Molecular;Mus;Nervous System Disorder;Neurobiology;neuropsychiatric disorder;novel;novel strategies;pathogen;Pathway Analysis;Patients;Positioning Attribute;Prefrontal Cortex;Process;programs;Proteins;Publishing;reference genome;Regulation;Repression;Research;resilience;response;RNA analysis;Rodent;Role;Schizophrenia;Scientist;skills;Social Behavior;social cognition;social deficits;Social Dominance;social group;Social Hierarchy;Social Interaction;social stress;Societies;Stress;stress resilience;synthetic biology;Testing;Therapeutic;Tissues;Training;Transcript;Transcription Coactivator;transcription factor;Transcriptional Regulation;transcriptional reprogramming;transcriptome sequencing;transcriptomic profiling;transcriptomics;Tube;Variant;Viral;Work;Zinc Fingers

PROJECT_TITLE: Reprogramming Transcription Factors to Study Social Behavior

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F02A-W(20)]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics;Microbiome

ORG_CITY: STANFORD

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Project Narrative The human intestinal microbiota is a diverse microbial ecosystem that carries out many essential functions for human health, such that a wide range of illnesses have been linked to an altered gut microbial community. This proposal will examine the roles, ecological relevance and evolutionary dynamics of a set of mobile genes that is shared by many gut bacteria and mediates biofilm formation. This knowledge will further our understanding of intestinal ecology and its recent changes in human populations, and will provide one more key step towards the design of reliable targeted microbiome interventions for therapeutic purposes.

PI_NAMEs: GARCIA-BAYONA, LEONOR  (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Adhesives;Affect;Anabolism;Antibiotic Therapy;Antibiotics;Architecture;Bacteroides;Bar Codes;Biopsy;Cells;China;cohort;Colon;Communities;cost;Costs and Benefits;Data;design;Dissection;DNA;Ecology;Ecosystem;Evolution;Exclusion;experimental study;extracellular;fitness;Food;Frequencies;Gene Exchanges;Genes;genetic element;Gnotobiotic;gut bacteria;gut microbiome;gut microbiota;Health;Health Benefit;Horizontal Gene Transfer;host-microbe interactions;Human;human microbiota;human subject;Human Volunteers;Image;improved;In Vitro;in vitro Assay;Individual;Inflammation;Inflammatory;interest;Intestines;Japanese;Knowledge;Life;Link;Location;Mediating;member;Mentors;Methods;Microbe;microbial;Microbial Biofilms;microbial community;microbiome;microbiome components;microbiome therapeutics;microbiota;Microscopy;Mobile Genetic Elements;mouse model;mucosal biofilms;Mucous body substance;Mus;particle;Persons;Phenotype;Physiologic pulse;Plasmids;Play;polymicrobial biofilm;Polysaccharides;Population;Population Dynamics;preservation;promote resilience;resilience;Role;sample fixation;Sampling;Shapes;Site;skills;Stains;Stress;stressor;Structure;Surface;synergism;targeted treatment;Techniques;Testing;Therapeutic Intervention;Training;Visualization

PROJECT_TITLE: Plasmid encoded biofilm formation by the intestinal Bacteroidales and its importance in community ecology and resilience

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: HANOVER

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: PROJECT NARRATIVE Wnt signaling is a biological pathway that allows cells to communicate and to coordinate their behavior during animal development, tissue maintenance, and regeneration. It is also often dysregulated across a wide variety of human diseases. We are working to discover the mechanisms that allow Wnt signals to induce the activation of genes and thereby regulate changes in cell growth and differentiation. Our discoveries will be applicable to new therapeutic strategies that regulate signaling in Wnt-driven developmental disorders and cancers.

PI_NAMEs: AHMED, YASMATH  (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Adenosine Diphosphate Ribose;Animals;Behavior;beta catenin;Biochemical;Biological;Biological Assay;Cell Differentiation process;cell growth;Cell Proliferation;Cells;Collaborations;Colorectal Cancer;combat;Communication;Complex;design;Development;developmental disease;Disease;Dissection;Drosophila genus;Gene Activation;Genetic;Genetic Transcription;genome wide screen;Goals;Homeostasis;human disease;in vivo;in vivo Model;innovation;Knowledge;Laboratories;Maintenance;Malignant Neoplasms;Mass Spectrum Analysis;Membrane;Modeling;Molecular;Monitor;Natural regeneration;novel therapeutic intervention;Nuclear;Pathway Analysis;Pathway interactions;Phosphotransferases;Polymerase;Post-Translational Protein Processing;Predisposition;Productivity;programs;receptor;Receptor Activation;reconstitution;Research;Research Personnel;Role;Scaffolding Protein;Signal Transduction;Signal Transduction Pathway;Tankyrase;therapeutic target;Tissues;Tumor Suppressor Proteins;ubiquitin ligase;WNT Signaling Pathway;Work

PROJECT_TITLE: Genetic and Molecular Dissection of Wnt Pathway ActivationSupplement

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


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Depression;Mental Health;Mental Illness;Neurodegenerative;Neurosciences

ORG_CITY: SAINT LOUIS

ORG_DEPT: PSYCHOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Healthy aging is associated with a striking paradox: As adults age, they typically have better control over their emotions while also simultaneously experiencing decline in cognitive functions and brain systems that have been associated with emotion regulation. This study will investigate the brain basis of emotion regulation in middle- and older-age adults, and how a history of depression might impact the typical pattern of age-related improvement in emotional control. Ultimately, the proposed research will help to improve quality of life for healthy older adults, while also providing treatment targets to prevent recurrence of depression for those with a depression history.

PI_NAMEs: ENGLISH, TAMMY  (contact);THOMPSON, RENEE J

PROGRAM_OFFICER_NAME: STOECKEL, LUKE

PROJECT_TERMS: Address;Adult;Affective;Age;age effect;age related;age related changes;age related decline;Behavior assessment;Behavioral;Brain;Cicatrix;Code;Cognitive;cognitive control;cognitive function;cognitive reappraisal;Cues;Data;Data Set;Decision Making;Depressed mood;design;Development;Diagnostic;Dimensions;Disease remission;Ecological momentary assessment;emotion dysregulation;emotion regulation;Emotional;emotional experience;emotional functioning;Emotions;Ethnic Origin;Exhibits;experience;Facial Expression;Foundations;Functional Magnetic Resonance Imaging;Goals;healthy aging;human old age (65+);Image;improved;Incentives;Individual;Individual Differences;individual variation;Influentials;innovation;insight;Intervention;Interview;Knowledge;Laboratories;Lateral;Learning;Life;Maintenance;Major Depressive Disorder;Matched Group;Measures;Mediating;meetings;Mental Depression;Mental disorders;Mental Health;Methods;middle age;Modeling;Motivation;neural;neural circuit;Neurobiology;neuroeconomics;neuroimaging;neuromechanism;normal aging;novel;Nucleus Accumbens;older adult;Participant;pathological aging;Patient Self-Report;Pattern;Personal Satisfaction;Persons;Play;Population;positive emotional state;Prefrontal Cortex;prevent;Process;Protocols documentation;Quality of life;racial diversity;Recording of previous events;recurrent depression;Research;response;reward processing;Rewards;Role;Sampling;Scanning;Self-control as a personality trait;side effect;Source;Standardization;success;System;Testing;therapeutic target;trait;Update;Variant;Ventral Striatum;Woman;Work

PROJECT_TITLE: Neural and motivational mechanisms of age-related change in emotion regulation

STUDY_SECTION: CP

STUDY_SECTION_NAME: Cognition and Perception Study Section[CP]


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;Neurosciences

ORG_CITY: SAN ANTONIO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: Project Narrative: The proposed research is relevant to public health because Alzheimer's disease (AD) is the most common cause of dementia worldwide. However, available therapies have not been shown to delay its onset or progression. The current application aims to understand a novel mechanism underlying lipid deficiency- induced activation of a type of brain cell (i.e., astrocytes) in AD. Positive results may lead to new understanding of AD pathogenesis and development of novel drugs for effective treatment of AD.

PI_NAMEs: HAN, XIANLIN  (contact)

PROGRAM_OFFICER_NAME: OPANASHUK, LISA A

PROJECT_TERMS: Acceleration;age related;Aging;aging related;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease risk;Alzheimer's disease therapy;Amyloid beta-Protein;Anabolism;Animal Model;Apolipoprotein E;apolipoprotein E-4;Astrocytes;astrogliosis;Behavioral;Blood;Brain;brain cell;brain dysfunction;Cells;Clinical;cognitive function;cognitive performance;Communication;Complex;CSF1R gene;Cyclodextrins;cytokine;Data;Dementia;Development;Disease;effective therapy;Elderly;Electron Microscopy;Etiology;Event;Extracellular Matrix Proteins;galactosylceramide sulfotransferase;Gender;Genes;genetic risk factor;Gliosis;Histologic;Homeostasis;Impaired cognition;Inflammatory Response;Inflammatory Response Pathway;inhibitor;Integrins;Interleukin Activation;Interleukin-6;Knockout Mice;Laminin;Late Onset Alzheimer Disease;LDL-Receptor Related Protein 1;life span;lipid metabolism;lipidomics;Lipids;LoxP-flanked allele;Mediating;Mediator;Metabolic;Metabolism;Microglia;Modeling;Molecular;mouse model;Mus;Myelin;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;neuropathology;novel;novel therapeutics;old mice;Older Population;Oligodendroglia;oncostatin M;overexpression;particle;Pathogenesis;Pathologic;pharmacologic;Phosphorylation;Play;prevent;Process;Protein Isoforms;Proteins;Public Health;Publishing;Reaction;receptor;Receptor Signaling;recruit;Regulation;Research;response;risk variant;RNA;Role;Secondary to;Signal Transduction;Slice;Stat3 protein;Sulfoglycosphingolipids;Testing;Therapeutic;Time;Up-Regulation;Vitamin K;Western Blotting;Work

PROJECT_TITLE: Sulfatide deficiency: A novel mechanism leading to reactive astrogliosis in aging and Alzheimer’s disease


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

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE Sleep is an essential pillar of human health and sleep disruption later in life is believed to be a source of vulnerability in the development of Alzheimer's disease (AD), a devastating neurodegenerative condition. The proposed study will examine the mechanisms of age-related sleep disruption and its impact on the synapse. Based on our molecular understanding of sleep's restorative processes, we will test the ability of new sleep- based medicines to limit AD progression or even to reverse age-related pathology and cognitive decline.

PI_NAMEs: COHEN, TODD JONATHAN;DIERING, GRAHAM HUGH (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: Acceleration;Acute;Affect;Age;age related;Age related pathologies;Aging;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease related dementia;Amyloid;amyloid pathology;anandamide;Automobile Driving;Behavior;Behavior Therapy;Behavioral;Biological Markers;Biological Models;Brain;brain health;Chemicals;Cognition;cognitive function;Data;Defect;Development;Disease;Disease Progression;Early Diagnosis;endocannabinoid signaling;Endocannabinoids;endogenous cannabinoid system;Etiology;Excision;Exposure to;Functional disorder;Genetic Models;Glutamate Receptor;Growth;Health;Hippocampus;Homeostasis;Human;human disease;Impaired cognition;Impairment;improvement on sleep;In Vitro;in vitro Model;Individual;inhibitor;insight;Intervention;Knockout Mice;Learning;Life;Link;Lipase;Maintenance;Measures;Mediating;Mediator;Medicine;Memory;Metabotropic Glutamate Receptors;Modeling;Molecular;mouse model;Mus;Nerve Degeneration;Neurofibrillary Tangles;Neurons;neurotoxic;novel;Onset of illness;Pathologic;Pathology;Patients;Performance;Pharmaceutical Preparations;pharmacologic;Phenotype;Physiological Processes;predictive marker;Process;Prosencephalon;Protein Dephosphorylation;Publishing;Regulation;Risk;Senile Plaques;Signal Transduction;Sleep;sleep behavior;Sleep disturbances;sleep quality;Sleep Wake Cycle;Source;Structure;Symptoms;Synapses;synaptic function;Synaptic plasticity;System;tau aggregation;tau interaction;tau mutation;tau Proteins;Tauopathies;Testing;Therapeutic;therapeutic evaluation;therapeutic target;Treatment Efficacy;Variant;Work

PROJECT_TITLE: Sleep-dependent synaptic homeostasis in Alzheimer's disease

STUDY_SECTION: CDIN

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


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Genetics;Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Aging and neurodegeneration are characterized by cognitive declines. We have discovered an evolutionary conserved but poorly understood steroid hormone that significantly improves learning capacity. We investigate the mechanistic basis of this improvement with the long-term goal of developing therapies.

PI_NAMEs: ASHRAFI, KAVEH  (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Affect;Age;Aging;Anabolism;animal old age;Animals;Behavioral Assay;behavioral plasticity;Binding;Biochemical;Brain;Caenorhabditis elegans;Cells;Chemicals;Data;Development;Disease;Enhancers;Enzymes;Estrogen Receptor 2;experimental study;Gene Expression;Generations;Genes;genetic manipulation;Genetic Screening;Genetic Transcription;Glycols;Goals;Head;High Pressure Liquid Chromatography;Homologous Gene;hormonal signals;Hormones;Human;Image;Impaired cognition;improved;insight;Interneurons;Investigation;Kynurenic Acid;Learning;Ligand Binding Domain;Ligands;Link;Mammals;Measurement;Measures;Mediating;Memory;Metabolism;Methodology;Molecular;Molecular Genetics;Monitor;Mus;N-Methyl-D-Aspartate Receptors;Names;Nature;Nerve Degeneration;Nervous System;neural;neuromechanism;Neurons;neuroregulation;novel;Nuclear Hormone Receptors;Nutritional status;Peripheral;pharmacologic;Phylogeny;Physiological;Physiology;Process;Production;Proteins;Puberty;Reagent;receptor;reconstitution;Regulation;Reporter;reproductive;Role;steroid hormone;Steroids;Suggestion;tandem mass spectrometry;Techniques;Testing;Therapeutic;Therapeutic Intervention;therapy development;Tissues;transcription factor;Tryptophan;Variant

PROJECT_TITLE: Regulation of learning and memory by steroid hormone signaling during development and aging

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Autosomal recessive polycystic kidney disease (ARPKD) is a rare disease that can cause kidney failure and liver complications and currently does not have any available FDA-approved treatments. Even though several drugs have appeared promising in animal studies, there are few clinical trials in humans due to a lack of detailed information about the natural history of ARPKD and difficulty in recruiting enough patients who are able and willing to take part in trials. The goal of this proposal is to accelerate clinical trials for ARPKD by creating PKDnet, a resource that will help to inform future clinical trial design by identifying children with ARPKD and efficiently collecting high quality, large-scale natural history data from PEDSnet, a large National Pediatric Learning Health System, and by performing patient and family surveys to identify research priorities and understand factors affecting willingness to participate in clinical trials.

PI_NAMEs: HARTUNG, ERUM AFTAB (contact)

PROGRAM_OFFICER_NAME: FERMAGLICH, LEWIS

PROJECT_TITLE: PKDNet - ARPKD Learning Network

STUDY_SECTION_NAME: Special Emphasis Panel[ZFD1 OC-S (01)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: This Project Narrative was originally submitted with R01 NS079518 and is included here unchanged to satisfy submission system requirements. PROJECT NARRATIVE This proposal examines the neural basis for how organisms make decisions about movements. Understanding neural activity in specific types of neurons under normal conditions, and how it is altered under pathological conditions, can contribute to improving treatments for movement disorders like Parkinson's disease.

PI_NAMEs: FELSEN, GIDON S (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Animal Model;Animals;awake;Behavior;Brain;Brain region;Contralateral;Cues;Decision Making;Distal;experimental study;Funding;Goals;improved;Left;Mediating;Midbrain structure;Motor;Motor output;mouse model;Movement;Movement Disorders;Mus;Nervous System Physiology;neural;neural circuit;Neurons;Odors;Organism;Outcome;Parkinson Disease;Pathologic;Population;Research;Rewards;Series;Shapes;Site;Slice;superior colliculus Corpora quadrigemina;System;Testing;Work

PROJECT_TITLE: Diversity supplement to Functional neural circuitry for decision making in the superior colliculus


ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

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

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

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

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

PROGRAM_OFFICER_NAME: PLUDE, DANA JEFFREY

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

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


ORG_CITY: Columbus

ORG_DEPT: CHEMISTRY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative This MIRA application seeks to uncover the specific functions of a growing family of trans-editing proteins that play a universal role in maintaining the fidelity of protein synthesis. Our knowledge of the broader physiological functions of these proteins, especially in eukaryotes, will be addressed in this work. The therapeutic potential of trans-editing domains has not been exploited and represents another major gap in the field that we hope to address by our planned studies.

PI_NAMEs: MUSIER-FORSYTH, KARIN M (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Address;Amino Acids;Amino Acyl-tRNA Synthetases;Aminoglycosides;Area;Bacteria;Cell Survival;Cells;deacylation;design;Drug Combinations;Eukaryota;Family;Genes;Genetic Code;Goals;Homologous Gene;In Vitro;infancy;knock-down;Knowledge;knowledge base;Lead;new therapeutic target;novel;pathogen;Physiological;Play;Process;proline-tRNA;Protein Biosynthesis;Protein Family;protein function;Protein Synthesis Inhibitors;Proteins;Quality Control;Research;Ribosomes;Role;Shapes;Solid;Structure;Therapeutic;therapeutically effective;Transfer RNA;Work

PROJECT_TITLE: Translational quality control by trans-editing domains


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: PITTSBURGH

ORG_DEPT: BIOLOGY

ORG_NAME: DUQUESNE UNIVERSITY

PHR: Relevance  We wish to understand how DNA is segregated and packaged in the special filamentous organisms that produce the majority of biologically active compounds used to treat bacterial infection and cancer. These organisms are major producers of the compounds that we all rely on for our health and quality of life. Basic knowledge of fundamental cell functions of these organisms may lead to better production of known and novel compounds, which may lower the cost of buying medicines.

PI_NAMEs: MC CORMICK, JOSEPH R (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Alanine;Anthelmintics;anti-cancer;anti-fungal agents;Antibiotics;Architecture;ATP phosphohydrolase;Bacteria;Bacterial Infections;Basic Science;Binding;Biotin;Cell Physiology;Cellulose;Characteristics;Chitin;Chromosome Segregation;Chromosomes;cost;Development;DNA;Environment;Genes;genetic approach;Genome;Goals;Health;Human;Immunosuppressive Agents;in vivo;Knowledge;Label;Life Cycle Stages;Ligase;Malignant Neoplasms;Medical;Medicine;Mutagenesis;mutant;novel;Nutrient;Odors;Organism;Pharmacologic Substance;Physical condensation;Polymers;Production;protein protein interaction;Protein Secretion;Proteins;Quality of life;Recycling;Reproduction spores;Scanning;segregation;Shapes;Soil;Streptomyces;Structure;System;tumor;Veterinary Medicine;Viral

PROJECT_TITLE: Development-Associated Linear Chromosome Segregation in Streptomyces


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Women's Health Research

ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PI_NAMEs: KERI, RUTH A. (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: Address;Affect;African American Women;anti-cancer research;Biology;Breast Cancer Cell;Breast Cancer Patient;breast cancer progression;Cancer Biology;cancer subtypes;Cellular biology;Centrosome;chemotherapy;Computational Biology;Cytoplasm;Data;density;Development;Disease;Disease Progression;Dryness;Education;EGFR gene;Elements;Endothelium;Environment;Epidermal Growth Factor Receptor;ERBB2 gene;Estrogen Receptors;Fibroblasts;follow-up;Fostering;Foundations;FOXM1 gene;Future;gene discovery;Gene Expression Profile;Gene Expression Profiling;Genes;Genetic;Genetic Transcription;Goals;Growth;Heterogeneity;Human;human disease;improved;Individual;inhibitor;interest;JUN gene;Laboratories;Language;Malignant Breast Neoplasm;Malignant Neoplasms;MAPK8 gene;member;Membrane;Messenger RNA;Mitosis;Mitotic;mRNA Expression;Mus;neoplastic cell;Non-Small-Cell Lung Carcinoma;parent grant;parent project;Parents;Pathway interactions;Patient-Focused Outcomes;Patients;Pattern;pharmacologic;protein expression;receptor;Recurrence;Regulatory Pathway;Research;Research Training;resilience;response;Role;Sampling;Series;Signal Transduction;skills;social;src-Family Kinases;Stains;standard of care;Supporting Cell;targeted agent;taxane;therapeutic target;therapy resistant;Tissue Microarray;Tissues;Training;Training Programs;transcription factor;transcriptome;transcriptomics;Treatment Efficacy;triple-negative invasive breast carcinoma;tumor;Tumor Biology;Xenograft procedure;YES1 gene

PROJECT_TITLE: Supplement - Discovering the role of YES1 in triple negative breast cancer


ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative About 1300 American children will develop intestinal failure each year; 30% of these children will die or need an intestinal transplant within 6 years. This proposal aims to combine the patient and family perspective with natural history data to support new drug development.

PI_NAMEs: AVITZUR, YARON ;HORSLEN, SIMON  (contact)

PROGRAM_OFFICER_NAME: HAGHPANAH, SEPIDEH

PROJECT_TITLE: Defining pediatric intestinal failure natural history


ORG_NAME: UNIVERSITY OF TEXAS SAN ANTONIO

PHR: PROJECT NARRATIVE Disease, degeneration, or traumatic injury of the nervous system are among the greatest public health concerns in the United States. Human ESCs and 3D neural organoid models raise hope that functional regeneration of nervous tissue may be feasible, if we understand the mechanisms that promote neurogenesis in human cell models. This research will lead to improved understanding of aberrant neurogenesis, possibly leading to the development of new treatments for mitigating epilepsy.

PI_NAMEs: HSIEH, JENNY  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: 3-Dimensional;Ablation;Acute;Address;Adult;adult neurogenesis;Animal Model;Animals;Brain;Brain Injuries;Candidate Disease Gene;Cell Cycle;Cell Maturation;Cell model;cell motility;Cells;clinically relevant;Clozapine;comparison control;controlled cortical impact;Dendrites;designer receptors exclusively activated by designer drugs;Development;digital;Disease;Epilepsy;Epileptogenesis;experimental study;Extracellular Matrix;Frequencies;Functional Regeneration;G-Protein-Coupled Receptors;Gene Expression;Gene Expression Regulation;Generations;Genes;granule cell;Hilar;Hippocampus;Human;human embryonic stem cell;Hypertrophy;Immunohistochemistry;improved;Injury;knock-down;Laboratories;Ligands;loss of function;Maps;Matrix Metalloproteinase Inhibitor;Mediating;migration;Modeling;Molecular;Morphology;mossy fiber;Motion;mouse model;Mus;Nerve Tissue;Nervous System Disorder;Nervous System Trauma;nestin protein;neural;neurogenesis;Neurons;novel;older adult;Organoids;Oxides;Parents;Pathway interactions;pharmacologic;Pilocarpine;Post-Traumatic Epilepsy;Process;Production;programs;Public Health;Publishing;Receptor Activation;Recurrence;Regulation;Research;Retroviridae;Role;Seizures;Signal Pathway;Signaling Molecule;small molecule;Status Epilepticus;Testing;therapeutic target;Thymidine Kinase;TIMP3 gene;Tissues;transcriptome sequencing;Transgenic Mice;Transgenic Organisms;Translating;Traumatic Brain Injury;Traumatic injury;United States;Wild Type Mouse;Work

PROJECT_TITLE: Molecular control of aberrant adult-born granule cells in epilepsy.


FUNDING_MECHANISM: RESEARCH CENTERS

NIH_SPENDING_CATS: Clinical Research;Infectious Diseases

ORG_CITY: LAWRENCE

ORG_NAME: UNIVERSITY OF KANSAS LAWRENCE

ORG_STATE: KS

PHR: PROJECT NARRATIVE The development of new chemotherapeutic approaches for the treatment of infectious disease is, by acclamation, one of the preeminent challenges of modern biomedical science. This Phase II proposal is designed to strengthen and enhance the investments and infrastructure established in Phase I for the Center for Chemical Biology of Infectious Diseases. The CBID Center will continue to address critical gaps and enable researchers at the University of Kansas (KU) and associated institutions to apply these tools to better understand and potentially prevent infectious diseases.

PI_NAMEs: HEFTY, P SCOTT (contact)

PROGRAM_OFFICER_NAME: BERNAL, FEDERICO

PROJECT_TERMS: Address;Animals;Area;base;Biological;Biological Models;Biology;Centers of Research Excellence;Chemicals;Chemistry;Chemotherapy-Oncologic Procedure;Collaborations;Communicable Diseases;Communities;Core Facility;Coupled;design;Development;drug discovery;Education and Outreach;effective therapy;expectation;experience;Faculty;high throughput screening;Infectious Agent;infectious disease treatment;Infrastructure;innovation;Institution;Intervention;Investments;Kansas;member;Mentors;Mentorship;Microbiology;Modernization;multidisciplinary;novel;Organism;Pathway interactions;Pharmaceutical Chemistry;Pharmacologic Substance;Pharmacology;Phase;Pilot Projects;prevent;Principal Investigator;Process;professor;programs;Proteomics;Public Health;recruit;Research;research facility;Research Personnel;Research Project Grants;Resistance;Resources;Science;Scientist;Series;success;Therapeutic;tool;United States National Institutes of Health;Universities;Validation;Work

PROJECT_TITLE: Chemical Biology of Infectious Disease


PHR: PROJECT NARRATIVE Transfer RNAs (tRNAs) are the universal adaptor molecules essential for protein synthesis in all living cells and their coordinated and accurate processing is critical to ensure production of a high-quality tRNA pool. Mutations in the human tRNA methyltransferase enzyme Trm10 are associated with a multi-faceted disease phenotype that indicates important functions for Trm10. This project will uncover how diverse Trm10 enzymes modify their specific tRNA substrates and the biological effects of the modification they introduce, to define the role of Trm10 in maintaining optimal cellular health and as a potential novel target for therapies for human disease.

PI_NAMEs: CONN, GRAEME L;JACKMAN, JANE ELIZABETH (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Address;Adopted;Amino Acid Sequence;analog;Archaea;Aspartic Acid-Specific tRNA;Award;base;Biochemical;biochemical tools;Biological;biological adaptation to stress;Biological Assay;Biological Models;Biological Process;Biology;Cell Physiology;Cells;Chemicals;cofactor;Complex;Cryoelectron Microscopy;Defect;dimer;Disease;disease phenotype;drug sensitivity;Endocrine;Ensure;Enzymatic Biochemistry;Enzymes;Eukaryota;Exhibits;Family;fitness;Functional disorder;Generations;Genetic;genetic approach;Genetic Code;Genetic Models;Health;Homologous Gene;Human;human disease;in vitro Assay;in vivo;Individual;insight;interdisciplinary approach;Investigation;Knowledge;Life;Ligation;loss of function;Maintenance;member;Methylation;Methyltransferase;Modeling;Modification;Molecular;monomer;mutant;Mutation;Neurologic;new therapeutic target;Nucleic Acids;Nucleotides;Organism;Orthologous Gene;Pathway interactions;Pattern;Phenotype;Positioning Attribute;posttranscriptional;Process;Production;Protein Biosynthesis;Proteins;Purine Nucleotides;Quality Control;Ribosomes;RNA;RNA Biochemistry;Role;S-Adenosylhomocysteine;S-Adenosylmethionine;Saccharomyces cerevisiae;Specificity;Structure;Substrate Specificity;Syndrome;System;Time;Tissues;Transfer RNA;Translations;tRNA Methyltransferases;yeast genetics;Yeasts;Zebrafish

PROJECT_TITLE: Mechanisms and biological functions of SPOUT methyltransferases


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Eye Disease and Disorders of Vision;Infectious Diseases;Neurosciences;Vector-Borne Diseases

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: The original Narrative document has not changed as a result of the proposed supplement activities.

PI_NAMEs: HOLMES, TODD C (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TITLE: UV to blue neuronal phototransduction mechanisms

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


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Diabetes;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prevention

ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

ORG_STATE: MI

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because the predisposing factors for metabolic disease are largely unknown. Due to ethical and technical limitations of human studies the demonstration of causality is impossible and mechanistic insights remain inaccessible. The project will use a newly developed mouse model to study how paternal exposure to benzene, a major air pollutant, triggers an alternative offspring developmental trajectory in offspring leading to increased susceptibility to metabolic disease.

PI_NAMEs: LEMPRADL, HEIDI  (contact);SADAGURSKI, MARIANNA

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Address;Adhesives;Air Pollutants;Behavior;Benzene;Benzene Exposure;bisulfite sequencing;blastocyst;cigarette smoke;Closure by clamp;Communication;Communities;Conceptions;Continuous Glucose Monitor;Data;Development;Diabetes Mellitus;Diet;Disease;Disease susceptibility;DNA Methylation;DNA methylation profiling;Dose;Embryo;Environmental Exposure;Epigenetic Process;Ethics;Etiology;Event;experience;Exposure to;Fathers;Fertilization;Gene Expression Profile;Gene Expression Profiling;Generations;Genetic Transcription;Germ Lines;glucose tolerance;glycemic control;Health;Heritability;Homeostasis;Human;Hyperglycemia;Hyperinsulinism;Impairment;improved;insight;Insulin;Insulin Resistance;Intercept;interest;intergenerational;Intervention;male;Measurable;Messenger RNA;Metabolic;Metabolic Diseases;Metabolic stress;Metabolism;Molecular;Motor Vehicles;mouse model;Nature;non-genetic;novel;Occupational Exposure;offspring;Oocytes;Paint;Paternal Exposure;Pattern;Petroleum;Pharmaceutical Preparations;pharmacologic;Phenotype;Physiological;Population;Predisposing Factor;Predisposition;prevent;programs;Public Health;Research;Risk;RNA;Rubber;Severities;sex;Signal Transduction;Small RNA;Solvents;Source;sperm cell;System;Testing;Time;Tissues;Tobacco smoke;transcriptome sequencing;transmission process;Vehicle Emissions;volatile organic compound;whole genome;zygote

PROJECT_TITLE: Molecular mechanisms underlying metabolic reprogramming by paternal benzene exposure

STUDY_SECTION: EDD

STUDY_SECTION_NAME: Environmental Determinants of Disease Study Section [EDD]


NIH_SPENDING_CATS: Aging;Biotechnology;Brain Disorders;Genetics;Huntington's Disease;Neurodegenerative;Neurosciences;Rare Diseases

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

PHR: NARRATIVE The proposed research is relevant to public health because the mitonuclear interaction is altered is altered in a number of different diseases including cancer, obesity, neurodegeneration, and aging. Given that the mechanisms regulating mitonuclear interaction are conserved from yeast to humans, understanding this genetic network may allow us to identify new therapeutic targets for potential interventions for human diseases associated with harmful consequences of mitochondrial dysfunction. Therefore, the research is relevant to NIGMS’s mission in supporting basic research that increases understanding of biological processes and laying the foundation for advances in disease treatment.

PI_NAMEs: KAYA, ALAATTIN  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Age;Aging;Basic Science;Biological;biological adaptation to stress;Biological Process;Cell Physiology;Cells;cellular engineering;Cellular Stress;Communication;Cytoprotection;Disease;fitness;Foundations;Functional disorder;Gene Expression;Genetic;Genome;Genotype;Goals;Haplotypes;Hemostatic function;heteroplasmy;Homeostasis;Human;human disease;Human Pathology;Huntington Disease;innovation;Intervention;Knowledge;Laboratories;Leber's Hereditary Optic Neuropathy;Link;Maintenance;Malignant Neoplasms;Metabolism;Mission;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial dysfunction;Modeling;Molecular;National Institute of General Medical Sciences;Nerve Degeneration;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear;Obesity;Pathway interactions;pharmacologic;Public Health;Research;Research Project Grants;Resistance;response;Role;Specificity;Stress;stressor;System;Testing;Yeasts

PROJECT_TITLE: The role of mito-nuclear communication in the adaptation to mitochondrial dysfunction and stress resistance

STUDY_SECTION: MRAD

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


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

ORG_CITY: WINSTON-SALEM

ORG_NAME: WINSTON-SALEM STATE UNIVERSITY

PHR: NIH SuRE Project Narrative  This NIH SuRE proposal aims to develop and utilize highly selective metal catalyzed carbon carbon bond formation reactions that will lead to efficient synthesis of novel selenium, sulfur, and oxygen-containing heterocycles with rich biological activities. Further elaboration of this chemistry will likely allow the first enantioselective synthesis of very important classes of heterocycles such as biselenoflavonoids, bithioflavonoids and bioactive biflavonoids, potential small molecule therapeutics for Alzheimer’s disease. This SuRE project is expected to significantly enhance and expand the research capacity towards a sustainable research excellence that actively involves underrepresented minority students in funded research at WSSU, a HBCU.

PI_NAMEs: GUO, FENGHAI  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Acylation;Alzheimer's disease therapeutic;Biological;biological systems;Carbon;Chemistry;Communication;Complex;Coupling;Development;drug discovery;enolate;Funding;Generations;Heterocyclic Compounds;In Situ;innovation;Metals;Names;Natural Products;Nature;novel;novel strategies;nucleophilic addition;oxidation;Oxygen;Pharmaceutical Preparations;Pharmacologic Substance;Process;Reaction;Reproduction;Research;Selenium;small molecule therapeutics;Sulfur;Therapeutic;underrepresented minority student;United States National Institutes of Health

PROJECT_TITLE: Development of Efficient Carbon Carbon Bond Formations for Novel Se-, S-, and O-Heterocycle Synthesis


NIH_SPENDING_CATS: Behavioral and Social Science;Child Abuse and Neglect Research;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;Mental Health;Pediatric;Primary Health Care;Rural Health;Social Determinants of Health;Violence Research;Youth Violence

ORG_DEPT: PSYCHIATRY

PHR: Project Narrative  Improving access to evidence-based mental health treatment is critical to improving outcomes for children who experience maltreatment. This study will develop and pilot strategies to improve multidisciplinary team functioning and facilitate implementation of a mental health screening and referral protocol in in rural Child Advocacy Centers. The proposed training and research will prepare the investigator to advance NIMH Strategic Objective 4.2 – “establish research-practice partnerships to improve dissemination, implementation, and continuous improvement of evidence-based mental health services” – and has the potential to positively impact public health by improving the capacity of systems in rural areas to meet the mental health needs of vulnerable children.

PI_NAMEs: MCGUIER, ELIZABETH ANN (contact)

PROGRAM_OFFICER_NAME: SWEENEY, MARY MARGARET

PROJECT_TERMS: Adoption;Advisory Committees;Advocate;Affect;Affective;Behavior;Behavioral;Behavioral Sciences;Businesses;California;Caregivers;Caring;Child;Child Abuse and Neglect;Child Advocacy;Child Mental Health;Child Welfare;Clinical;Clinical Sciences;cognitive process;cohesion;Committee Members;Communication;community based research;community partners;Competence;Conflict (Psychology);Data;Development;Education;effectiveness/implementation hybrid;Eligibility Determination;Ensure;evidence base;Evidence based practice;Evidence based treatment;experience;Goals;health care settings;Health Personnel;hybrid type 2 trial;Hybrids;Impairment;implementation efforts;implementation facilitation;implementation outcomes;implementation process;implementation science;implementation strategy;implementation/effectiveness;Improve Access;improved;improved outcome;Intervention;intervention mapping;Interview;Law Enforcement;maltreatment;member;Mental Health;Mental Health Services;Mentors;Mentorship;Methods;Modeling;multidisciplinary;National Institute of Mental Health;Outcome;Partnership Practice;patient safety;Pediatrics;peer;Penetration;Pennsylvania;Performance;pilot trial;Play;Positioning Attribute;post implementation;Primary Care;Process;professor;Protocols documentation;Psychiatry;Psychology;Public Health;Randomized;Recommendation;Replicating Effective Programs;Research;Research Personnel;Resources;response;Rewards;Rice;Risk;Role;routine practice;Rural;rural area;Rural Health Services;Schools;screening;Screening procedure;Service setting;skill acquisition;skills;Speed;Standardization;stress symptom;Structure;suicidal;Suicide;suicide rate;Surveys;System;team-based care;Testing;theories;tool;Training;Translational Research;traumatic stress;Universities;Utah;Vulnerable Populations;Washington;Youth

PROJECT_TITLE: Improving access to mental health services for rural youth: Leveraging multidisciplinary teams to enhance implementation of a screening and referral protocol in rural Child Advocacy Centers

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


ORG_CITY: Aurora

PHR: Parent Grant 5R35GM146923-02 Narrative: Intermediate filaments are abundant cytoskeletal proteins that interact with numerous cellular proteins and contribute to a variety of cellular processes, yet we lack a complete mechanistic understanding of their function. Here we propose to interrogate how intermediate filaments are regulated and how they contribute to inflammation by focusing on the intermediate filament vimentin and its role in neutrophil inflammatory processes and trafficking. The successful completion of this proposal is highly likely to identify new mechanisms by which intermediate filaments contribute to inflammation and to cellular and tissue function.

PI_NAMEs: RUSSO, BRIAN  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TITLE: The role of intermediate filaments during inflammation


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Palliative Care

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: PROJECT NARRATIVE There is a need to mentor junior clinical investigators with the research skills to improve care for persons living with Alzheimer's disease and related dementias (ADRD) and family care partners. As a geriatrician and ADRD researcher, Dr. Hillary Lum's research activities will enhance the science of engagement involving persons living with dementia and their care partners, and her mentorship activities will focus on enhancing the pipeline of ADRD investigators who progress to independent research careers that prioritize the needs of persons living with dementia and their care partners. Note: This file is identical to that submitted for the parent award and is attached to meet system requirements.

PI_NAMEs: LUM, HILLARY  (contact)

PROGRAM_OFFICER_NAME: FAZIO, ELENA

PROJECT_TERMS: Address;advanced dementia;Affect;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;career;Caring;certificate program;Clinical Investigator;Clinical Trials;Collaborations;collaboratory;Colorado;Communities;community engaged research;community engagement;community involvement;community organizations;Dementia;dementia care;design;Discipline;Doctor of Philosophy;Elderly;Equity;equity, diversity, and inclusion;Ethics;experience;Faculty;Family;Fellowship Program;Funding;Geriatrics;Goals;Grant;health equity;health information technology;Health Priorities;Health system;Healthcare;improved;Individual;informal care;Institution;Intervention;investigator training;Justice;Latino;Lead;Leadership;Lived experience;Medicine;member;Memory;Mentors;Mentorship;Methods;Mid-Career Clinical Scientist Award (K24);Midcareer Investigator Award in Patient-Oriented Research;mild cognitive impairment;multidisciplinary;National Center for Advancing Translational Sciences;Neurology;Nursing Faculty;older adult;online resource;Outcome;Palliative Care;Palliative Medicine;parent project;Parents;patient oriented;patient oriented research;Patients;peer;Persons;Physicians;Postdoctoral Fellow;Process;programs;Publications;Recommendation;recruit;Research;Research Activity;research faculty;Research Methodology;Research Personnel;Role;Scholars Program;Science;skills;System;Testing;therapy design;Time;timeline;tool;Training;Training Activity;Underserved Population;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: DEIA Mentorship Related to Engaging Persons with Alzheimer's Disease and Care Partners to Advance Dementia Research


ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: No changes being proposed.

PI_NAMEs: EICHMAN, BRANDT F (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: biological adaptation to stress;DNA biosynthesis;structural biology

PROJECT_TITLE: Structural Biology of the DNA Replication Stress Response


ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Primary cilia are microtubule-based projections on virtually every cell type and are linked to multiple signaling pathways. Among the best studied is Sonic hedgehog (Shh), which requires the cilium for signal transduction. Here we use a series of mouse models to genetically uncouple ciliogenesis and vertebrate Hh signaling, and in the process paint a clearer mechanistic picture of each. These proposed experiments have great potential to give us the fundamental knowledge we need to develop strategies to treat diseases related to abnormal cilia or Shh signaling.

PI_NAMEs: CASPARY, TAMARA J. (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Affect;Base Pairing;cell type;Cilia;cilium biogenesis;Cilium Microtubule;Comprehension;Disease;Dissection;Engineering;experimental study;Family;Genetic;Genetic Screening;Guanosine Triphosphate Phosphohydrolases;hedgehog signal transduction;in vivo;Individual;interest;Knowledge;Link;Molecular Genetics;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;neurodevelopment;Organelles;Paint;Pathway interactions;Process;Proteins;Regulation;Resolution;Role;Scientist;Series;SHH gene;Signal Pathway;Signal Transduction;smoothened signaling pathway;Structure;Variant;virtual

PROJECT_TITLE: Diversity Supplement to Genetic Dissection of Signaling and Cilia


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: HOUGHTON

ORG_NAME: MICHIGAN TECHNOLOGICAL UNIVERSITY

PHR: Research Strategy Our NIH award 1 R15GM152969-01 entails the synthesis and characterization of fluorescent-based probes operating in the red to near-infrared region to determine pH levels within organelles. It is critical to produce probes that would function ratiometrically as that would negate erroneous measurements based on differential diffusion rates. The syntheses of these probes involve many steps and at the end of each stage, as the compounds cannot be separated based on solubility differences, silica gel chromatography is employed. This requirement ends up adding days to the synthesis. Chromatography requires lots of glassware to do the synthesis and collect all the various fractions, not to mention the huge quantities of solvents such as dichloromethane that are utilized in these steps. Great skill is also required to prepare the columns and, while this is quite constructive, some preps are not as good as others and, in some cases, effective separation of the compounds is not accomplished. Unfortunately, we do not possess such a system in our laboratories. Our synthesis schemes are very involved,1-23 and we are going to use this equipment to purify compounds at every step of the process. We propose acquiring a preparative high-pressure liquid chromatography (HPLC) system for the purification of our reaction products, moving away from the conventional approach involving silica gel packed columns. This shift is driven by the superior capabilities of preparative HPLC, which excels in achieving enhanced resolution and improved separation of closely related compounds. Our decision is grounded in the intricate nature of our probes, composed of multiple fluorophore components linked through complex, multi-step synthetic procedures, where traditional packed silica gel column chromatography used in organic labs is often incapable of effectively separating side products with subtle structural variations. An example of one synthetic pathway is shown below. OO ,O  O  HO Pd(PPh3)4 HO  N Toluene, water O DCC, DMAP HN Toluene, acetic acid, isopropylamine  I O H O Dean Star apparatus  26 OH 100 oC, 8-h OH CH2Cl2  OH reflux OH O H HOOC O CH3SO3H N O N O H2N R1O R1  100 oC, 5 h (HO)2B OH N O R1O N  COOH I 29 O 30 25 27 28 OH 31 OOH  OR1 or  group BN OR1  R1 , sodium ascorbate, THPTA 32 FF N OR1 33 N  CuSO4 FB OR1 O H O FN  O R1 HN R1 HN N3 O O NH OS NH2 R HN O O O O 8O OH OH 36a OH R  HN  OR1 OR1 OR O  N3 O N OH  OR1 OR1 O 8 HN O OR OR HN O HN O O N 36b N  F B N FNB N FFB N  HN O OR  OH F OH F O OH N  35 N3 O O NH S Probe A1 OH FFB N  34 36c O SO3  N3 N Probe A2  R1O OR1 N or RO OR  R1 O P  N3 O 8 36e  N R Where  36d N N N N SO3  NN NN NN N O P  R group N O O N O N N O O Br N N  O NH S NH2 O O NH S 8  8 8O O  O 8 O amphiphilic zwitterion moiety  Goblegni zaepnpeasrautlufosn-sapmeicdiefic Lysomsoormpeh-oslpineecific Mitochondria-specific Cell membrane-specific  ER-specific p-toluenesulfonamide triphenylphophonium bromide Preparative HPLC provides the advantage of employing different stationary phases and fine-tuning mobile phase conditions, allowing targeted separation of complex reaction mixtures. The increased plate counts associated with HPLC columns further facilitate efficient separation, especially when dealing with high load volumes necessary for preparative-scale purifications. This not only ensures the production of higher purity products but also expedites the purification process. In the specific context of our probes, incorporating oligo(ethylene glycol) moieties with organelle-specific functional groups, preparative reverse phase HPLC is particularly advantageous. It enables the use of water-rich mobile phases, overcoming the limitations associated with silica gel normal phase column chromatography, which utilizes organic solvents that could excessively solubilize polar products, resulting in broad peaks and co-elutions. With preparative HPLC, we gain precise control over solvent strength, yielding tight, concentrated bands that can be efficiently collected at the preparative scale. Rationale: High-performance liquid chromatography is an essential technique in modern analytical chemistry, allowing for the separation, identification, and purification of chemical compounds. The preparative column with a refractive index detector is particularly valuable for our research, and the chosen system offers the following advantages:  1. High-Resolution Separation: The HPLC preparative column will provide high-resolution  separation of complex mixtures, allowing us to isolate target compounds with greater precision.  2. Purification Capability: The preparative column we are hoping to obtain is designed for 1 g of  material, making it suitable for the purification of compounds at preparative scale, a critical  aspect of our research objectives.  3. Refractive Index Detection: This will enable the detection and quantification of compounds  based on differences in their refractive indices. This will be useful for the separation of all  molecules as it is non-selective and responds to everything coming off a column. Unlike UV  detection, it does not rely on chromophores in the mixtures. Additionally some compounds have  weak UV absorptions. In essence it provides universal detection of compounds.  4. Reverse Phase: As the system is reverse phase, water or a water-based solvent can be used in the  mobile phase. This has many advantages over normal phase HPLC including lower costs  compared to other HPLC methods, less toxicity, accurate results, reduced solvent evaporation (as  polar solvents utilized), can change pH to affect separation, elimination of skewed analyte  retention times, and increased accuracy of gradient separations.  5. Non-toxic solvent use: Finally, another significant advantage is the ability to analyze samples  containing polar (hydrophilic), non-polar (hydrophobic), ionic, and ionizable compounds, due to  the use of a hydrophobic stationary phase. Benefits to NIH: The acquisition of the proposed HPLC preparative column with a UV detector will not only advance our research capabilities but also align with the NIH's mission to support groundbreaking scientific discoveries. The resulting research outcomes will contribute to the understanding of ratiometric fluorescent probes, with implications for the development of new diagnostic tools, therapeutic agents, or other applications that align with the NIH's broader goals. Conclusion: The acquisition of a preparative HPLC system is motivated by its unparalleled resolving power, flexible solvent options, and scalability in purifications. This strategic shift addresses the challenges inherent in the composition of our probes, ensuring efficient and high-quality purification tailored for their intended biomedical imaging applications. The chemistry department will maintain and preserve this instrument beyond the 3-year timeline of the NIH proposal GM152969. A confirmation letter from the department chair Dr. Athar Ata is attached.

PI_NAMEs: LUCK, RUDY LIN (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: absorption;Acetic Acids;Address;Affect;amphiphilicity;Analytical Chemistry;ascorbate;Award;biomedical imaging;Bromides;Cell membrane;Chemicals;Chemistry;Chromatography;chromophore;Column Chromatography;Complex;Complex Mixtures;cost comparison;Department chair;design;Detection;detector;Development;diagnostic tool;Diffusion;Ensure;Equipment;ethylene glycol;evaporation;flexibility;Fluorescent Probes;fluorophore;functional group;Funding;Gel Chromatography;Goals;High Pressure Liquid Chromatography;hydrophilicity;Hydrophobicity;improved;instrument;Laboratories;Letters;Link;Measurement;Measures;Methods;Methylene Chloride;Mission;Mitochondria;Modernization;Nature;novel diagnostics;Oligonucleotides;Organelles;Organic solvent product;Outcomes Research;Pathway interactions;Phase;preservation;Procedures;Process;Production;Pump;ratiometric;Reaction;Reflux;Refractive Indices;Research;Resolution;Sampling;Scheme;Side;silochrome;skills;Sodium;Solubility;Solvents;System;Techniques;Therapeutic Agents;timeline;Toluene;Toxic effect;United States National Institutes of Health;Variant;Water

PROJECT_TITLE: Preparative binary pump HPLC system with UV and refractive index detector capabilities


NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: We seek to construct biocompatible chemical tools that can interrogate the dynamic molecular events of living systems across space and time. By embedding highly eﬃcient reactions within 2D/3D nucleic acid scaﬀolds, we will build toolkits with the speed and sensitivity to capture the deep complexity of living cells and tissues. With architectures that can translate chemical events into new sequence information, we aim to erase boundaries between in vivo chemistry and nucleic acid biotechnologies, transforming (bio)molecular tracking and sensing.

PI_NAMEs: CARLSON, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TITLE: Bioorthogonal temporospatial tools - Admin Supple Equipment

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


NIH_SPENDING_CATS: Bioengineering;Infectious Diseases

ORG_DEPT: PHYSICS

ORG_NAME: CARNEGIE-MELLON UNIVERSITY

PHR: Project Narrative Many pathogenic bacteria are notorious for surviving harsh environments, adapting to different niches in the human body, and developing tolerance to drug treatments, all examples of phenotypic plasticity. Cellular organizations, as a hallmark of cell phenotype, dictate the physiological state and fitness of bacteria, and unraveling the origins and consequences of its plasticity is key to understanding the survival, growth, adaption, and drug tolerance of pathogenic bacteria. Exploring the optimality principles for the cellular organization could help identify bottlenecking cellular processes that can serve as non-molecular-specific targets with minimal concerns of rising drug resistance.

PI_NAMEs: SI, FANGWEI  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Algorithms;antibiotic tolerance;Bacteria;Bacterial Infections;Behavior;Biological Process;Biomedical Engineering;Biophysics;Cell Death;Cell membrane;Cell Physiology;Cells;Cessation of life;Chemicals;Collaborations;Communities;Computer software;Crowding;Data Set;density;Drug resistance;Drug Tolerance;Environment;Escherichia coli;experimental study;fitness;Fostering;Goals;Growth;Hallmark Cell;Human body;human pathogen;Image Analysis;Knowledge;laboratory experience;Life;Membrane;Membrane Proteins;Microfluidic Microchips;model organism;Modeling;Molecular Biology;non-genetic;operation;Organism;Outcome;pathogen;pathogenic bacteria;Pharmacotherapy;Phenotype;physical model;physical property;Physics;Physiological;Physiology;Positioning Attribute;Protein Databases;Proteins;Pseudomonas aeruginosa;Publishing;Research;Testing;tool

PROJECT_TITLE: Gauging how the plasticity of cellular organizations dictates growth, death and adaptation in single bacterial cells

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(54)-R]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease

ORG_CITY: SAN JUAN

ORG_NAME: UNIVERSITY OF PUERTO RICO MED SCIENCES

ORG_STATE: PR

PHR: PROJECT NARRATIVE Several cell death types are involved in the pathogenesis of myocardial infarction and ischemia- reperfusion injury. This project will elucidate the role of ferroptosis, a recently discovered cell death mechanism, in cardiac dysfunction induced by ischemia-reperfusion. These studies will be useful for the development of new therapeutic strategies to mitigate cardiac ischemia-reperfusion injury by targeting ferroptotic cell death.

PI_NAMEs: TORRES-RAMOS, CARLOS A (contact)

PROGRAM_OFFICER_NAME: REVILLEZA, MARIA

PROJECT_TERMS: Apoptosis;Cardiac;Cardiac Myocytes;Cell Death;Cells;Citric Acid Cycle;comparative;Coronary heart disease;coronary perfusion;Cysteine;Development;dihydrolipoic acid;effectiveness evaluation;Exposure to;Generations;Glutamates;glutathione peroxidase;Heart;heart damage;inhibitor;innovation;Iron;Ischemia;Mediating;Mitochondria;Molecular;Morbidity - disease rate;mortality;Myocardial dysfunction;Myocardial Infarction;Myocardial Ischemia;Myocardial Reperfusion Injury;novel;novel therapeutic intervention;Pathogenesis;Phosphatidylethanolamine;Phospholipids;Production;Reduced Glutathione;Reducing Agents;Reperfusion Injury;Reperfusion Therapy;response;Role;selenoprotein;Severities;Severity of illness;Signal Transduction;specific biomarkers;System;Techniques;Therapeutic;therapeutically effective;treatment strategy

PROJECT_TITLE: Mitochondria-mediated mechanisms of ferroptosis in response to cardiac ischemia-reperfusion injury


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: ITHACA

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative Improving our ability to recover from injuries like heart attacks and strokes is a major goal of regenerative medicine. Stem cells produce new tissues after injury, but we do not fully understand the mechanisms that control their behavior. This proposal will leverage the unlimited regenerative capacity and abundant stem cell population in planarian flatworms to identify the signaling pathways that control stem cell responses to surgical injuries.

PI_NAMEs: ADLER, CAROLYN ELIZABETH (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Apoptosis;Automobile Driving;Behavior;Biochemistry;cell behavior;Cell Cycle;Cell Cycle Arrest;Cell Differentiation process;Cells;Chemicals;Cues;design;differentiation in vitro;DNA Repair;embryonic stem cell;flexibility;forkhead protein;Foundations;Future;gene conservation;Goals;Homeostasis;improved;Injury;lens;Methods;Mitogen-Activated Protein Kinases;model organism;Molecular;Monitor;Myocardial Infarction;Natural regeneration;Organ;organ regeneration;Pathway interactions;Pharmacology;Pharyngeal structure;Physiological;Planarians;Platyhelminths;Pluripotent Stem Cells;Proliferating;Radiation;receptor;regenerative approach;Regenerative capacity;Regenerative Medicine;response;response to injury;RNA Interference;Role;Signal Pathway;Signal Transduction;single cell sequencing;stem cell differentiation;stem cell population;stem cell proliferation;stem cells;Stroke;Surgical Injuries;Technology;Testing;tissue regeneration;Tissues;Up-Regulation

PROJECT_TITLE: Mechanisms driving stem cell responses to injury in planarians


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: NORMAN

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF OKLAHOMA

ORG_STATE: OK

PHR: Project Narrative The supplement fund is requested under PA-20-272, NOT-OD-24-048, and NOT-GM-24-021 to purchase a light scattering device for the NIGMS R01 funded research. The device will accelerate the development of the next generation intracellular delivery platform for cell engineering. The proposed approach has the potential to provide advanced genetic modifications that are required to treat advanced diseases such as solid tumor immunotherapy and neurodegenerative diseases.

PI_NAMEs: YOON, SANGPIL  (contact)

PROJECT_TERMS: Acceleration;Acoustics;advanced disease;Area;Bacteria;Behavior Control;Binding;Biological Assay;Biotinylation;Blood - brain barrier anatomy;cell killing;Cell Line;Cell Survival;cell type;Cells;cellular engineering;Chimeric Proteins;Clinic;Clinical;clinical application;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Contrast Media;design;Development;Device or Instrument Development;Devices;Diagnosis;Disease;disease diagnosis;Drug Delivery Systems;effective therapy;Frequencies;Funding;Future;gas vesicle protein;Gases;Gene Delivery;gene editing technology;Gene Expression;Genes;Genetic;genome editing;Goals;Human body;Image;In Situ;In Vitro;in vivo;Individual;individualized medicine;innovation;Laboratories;light scattering;macromolecule;Mammalian Cell;manufacturability;Measures;Mediating;Medical;Methods;Microbubbles;Modification;monomer;Mus;nanoparticle;Nanostructures;National Institute of General Medical Sciences;neoplasm immunotherapy;Neurodegenerative Disorders;next generation;novel;off-target mutation;Particle Size;Penetration;Permeability;plasmid DNA;process improvement;Production;protein expression;Proteins;Radial;Recovery;Research;Resolution;Ribonucleoproteins;Safety;Sampling;scale up;side effect;Solid Neoplasm;spatiotemporal;Specificity;Streptavidin;System;T-Lymphocyte;targeted treatment;Techniques;Testing;theranostics;Therapeutic;tool;TP53 gene;Transfection;translational applications;tumor;ultra high resolution;Ultrasonic Therapy;Ultrasonic Transducer;Ultrasonography;ultrasound;Vesicle

PROJECT_TITLE: Light scattering device for the development of protein clouds


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Genetics

ORG_CITY: NEW YORK

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative We focus on highly characterized bacterial RNA polymerases, which have a high degree of conservation of structure and function from bacteria to man. The bacterial RNA polymerase is a proven target for antimicrobials, such as rifampicin (or its derivatives), widely used in combination therapy to treat tuberculosis, but bacterial strains resistant to rifampicin arise with appreciable frequency, compromising treatment. Insights into the mechanism of bacterial transcription, as well as into the inhibition mechanism of inhibitors, can lead to new avenues for the development of antimicrobials.

PI_NAMEs: DARST, SETH A. (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Antibiotics;antimicrobial;Bacteria;Bacterial RNA;Behavior;Binding;Biology;Chemicals;Combined Modality Therapy;Complex;Cryoelectron Microscopy;Development;Dissociation;DNA;DNA-Directed DNA Polymerase;DNA-Directed RNA Polymerase;Elements;Enzymes;Frequencies;Gene Expression;Genetic Transcription;Goals;Holoenzymes;inhibitor;insight;interest;man;melting;Methods;Molecular Conformation;Molecular Machines;Prokaryotic Cells;promoter;Regulation;resistant strain;Rifampicin resistance;Rifampin;RNA;Series;small molecule;structural biology;Structure;three dimensional structure;Transcript;transcription termination;tuberculosis treatment;Visualization

PROJECT_TITLE: Structure, function, and regulation of the bacterial transcription cycle


ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Administrative Supplement for Equipment - GM122917 Margaret A. Titus, PI Project Narrative  The metastatic spread of cancer cells relies on the ability of these cells to invade into tissue surrounding the tumor. Cancer cells use specialized structures called filopodia to move through tissues and spread throughout the body. The work in this proposal will define how cells make filopodia and will thus aid in the development of therapeutics to block their formation.

PI_NAMEs: TITUS, MARGARET A (contact)

PROJECT_TERMS: 3-Dimensional;Actins;Administrative Supplement;Biological Models;cancer cell;cancer invasiveness;cell motility;cell type;Cells;Computer Models;crosslink;Dictyostelium;Environment;Equipment;ezrin;Filopodia;Goals;in silico;In Vitro;in vivo;Invaded;Knowledge;Length;Membrane;Microfilaments;migration;Modeling;moesin;Molecular;Motor;Myosin ATPase;Neurons;Nonmuscle Myosin Type IIA;parent project;polymerization;Polymers;Process;Property;Proteins;radixin protein;Role;Structure;Tail;therapeutic development;Tissues;tumor;vasodilator-stimulated phosphoprotein;Work

PROJECT_TITLE: Mechanism of myosin motor-dependent filopodia formation


NIH_SPENDING_CATS: Brain Disorders;Genetics;Huntington's Disease;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: ALBANY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT ALBANY

PHR: Project Narrative The CAG microsatellite expansion diseases are a large group of rare neurodegenerative and neuromuscular diseases including spinocerebellar ataxias (SCAs) and Huntington’s disease (HD). Our preliminary data and lessons learned from other repeat expansion disease suggest that targeting the repeat expansion mutation that underlies many of these SCAs and HD will provide therapeutic potential across multiple diseases. Here we will test whether CAG SCA lead candidate compounds are capable of providing therapeutic benefit in HD models and whether combining our RNA regulating compounds with protein regulating compounds can enhance this therapeutic benefit.

PI_NAMEs: BERGLUND, ANDREW  (contact);SHIN, DAMIAN SEUNG-HO;SHORROCK, HANNAH

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Alternative Splicing;CAG repeat;Daphne plant;Data;design;Development;Disease;disease model;experience;Family;FDA approved;Fibroblasts;Genes;Huntington Disease;Huntington gene;Individual;Investigation;lead candidate;Microsatellite Repeats;MJD1 protein;Molecular;Mus;Mutation;Natural Products;Neurodegenerative Disorders;Neuromuscular Diseases;novel;parent grant;Pathogenesis;Pathogenicity;Patients;polyglutamine;preclinical development;Production;Proteins;Publishing;RNA;small molecule;small molecule therapeutics;spinal and bulbar muscular atrophy;Spinocerebellar Ataxias;symptom treatment;Testing;Therapeutic;therapeutic development;Training;Transcript;Treatment Efficacy;Type 1 Spinocerebellar Ataxia;Work

PROJECT_TITLE: Alternative Splicing and Development of Small Molecule Therapeutics in CAG Expansion Spinocerebellar Ataxias


NIH_SPENDING_CATS: Biotechnology;Natural Products

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: The botulinum neurotoxins are some of the deadliest known yet are also revered for their pharmaceutical utility. These toxins are marvels of protein evolution able to inject a toxic cargo enzyme into a specific cell type using a self-contained delivery system. Our unique combination of expertise in single molecule imaging, molecular simulations and protein-engineering will allow us to answer long- standing questions about the delivery mechanism by overcoming the structural heterogeneity that challenged previous studies.

PI_NAMEs: BOWEN, MARK E (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Administrative Supplement;Award;Botulinum Toxins;cell type;Chromatography;Enzymes;equipment acquisition;Evolution;experimental study;fast protein liquid chromatography;Fluorescent Dyes;Funding;Heterogeneity;instrument;Intoxication;Methods;Molecular;molecular imaging;parent project;Pharmacologic Substance;pressure;Protein Engineering;Proteins;Recombinant Proteins;Sampling;simulation;single molecule;structural biology;System;Toxin

PROJECT_TITLE: Resolving the intoxication mechanism of botulinum neurotoxins using single molecule structural biology

STUDY_SECTION: MSFC

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


ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PI_NAMEs: FARBER, DONNA L. (contact);SIMS, PETER ALAN

PROGRAM_OFFICER_NAME: HODGE, DEBORAH


ORG_CITY: CHAPEL HILL

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PARENT PROJECT NARRATIVE Defects in chromatin organization, gene transcription, and DNA packaging are major causes of human disease, notably cancer. Our studies will uncover the functions of readers and writers of histone post-translational modifications and histone variants, as well as the function of a histone chaperone complex. These studies will advance our fundamental understanding of the chromatin regulators that are dysregulated in human disease, thereby identifying new targets for therapeutic intervention.

PI_NAMEs: STRAHL, BRIAN D (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Address;Area;ASH1L gene;Award;Binding;Biological Models;Biology;casein kinase II;cell growth;Cells;Chromatin;chromatin remodeling;Complex;Decision Making;Defect;Development;Disease;DNA Methylation;DNA Packaging;DNA Repair;Enzymes;Event;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;Genome;Genomics;Goals;Histone Code;Histones;Homologous Gene;Human;human disease;Knowledge;Maintenance;Malignant Neoplasms;Metabolic;Modification;Molecular;Molecular Chaperones;Mouse Embryonic Stem Cells;Mutation;N-terminal;new therapeutic target;novel;Nucleosomes;parent project;Phosphorylation;Post-Translational Protein Processing;preference;Process;Proteins;Proteomics;Reader;Reading;Regulation;Repression;Research;Research Design;Seminal;Techniques;Therapeutic Intervention;Transcription Elongation;Transcriptional Regulation;Variant;Writing;Yeasts

PROJECT_TITLE: Mechanisms of chromatin and transcriptional regulation

STUDY_SECTION: MRAA

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


PHR: Our project endeavors to enhance the synthesis of fluorescent probes for biomedical sensing and imaging applications by integrating the state-of-the-art Shimadzu LCMS-2050 system, facilitating real-time monitoring and efficient optimization of synthetic methods, all while prioritizing sustainability and resource efficiency to reinforce our dedication to scientific innovation.

PI_NAMEs: LIU, HAIYING  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Acceleration;Adopted;Biomedical Research;candidate identification;Cells;Chemicals;Computers and Advanced Instrumentation;Consumption;Cost Savings;data integration;Decision Making;Dedications;Detection;Development;Discipline;empowerment;Engineering;Ensure;Environment;Feedback;Fluorescent Probes;Friends;Hazardous Waste;Height;Image;innovation;instrument;Investments;Laboratories;lead candidate;liquid chromatography mass spectrometry;Manuals;Methodology;Methods;Monitor;NADH;next generation;novel;Positioning Attribute;Practice Management;prevent;Process;Protocols documentation;Reaction;Reagent;real time monitoring;Research;Resources;screening;Secure;Stream;System;Technology;Time;tool;wasting

PROJECT_TITLE: Near-infrared Fluorescent Probes for Sensitive Detection of NADH in Live Cells


ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Project Narrative  The application of chemical properties to alter the reactivity of reagents for the synthesis of biomedically important compounds provides an opportunity to enhance the biomedical sciences. The chemical properties of hydrogen-bond-donor organocatalysts will enable the general, selective synthesis of 2-deoxy-β-glycosides, which remains elusive despite the importance of carbohydrates in biological systems, biological chemistry and medicine. Additionally, the properties of sulfur and the C–S bond will provide novel photochromic materials, addressing the stagnant synthetic approach to Stenhouse adducts, which are used in drug delivery, dynamic phase transfer, polymers, liquid crystals, wavelength-selective photoswitching, and chemosensing applications.

PI_NAMEs: PICAZO, ELIAS  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Strategic Molecular Activations for the Selective Synthesis of 2-Deoxy-Beta-Glycosides, and for the Synthesis of Novel Donor-Acceptor Stenhouse Adducts


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Down Syndrome;Infectious Diseases;Intellectual and Developmental Disabilities (IDD);Lung;Pediatric

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: Public Health Relevance Statement: We will elucidate the mechanism mediating the dysregulation of airway antiviral and antioxidative responses in Down Syndrome (DS). This may provide the foundation to develop novel approaches to prevent severe respiratory infections caused by RSV and other viruses (e.g. SARS-CoV-2) in children and adults with DS.

PI_NAMEs: JAISWAL, JYOTI K;NINO, GUSTAVO  (contact)

PROGRAM_OFFICER_NAME: SOOD, BEENA G

PROJECT_TERMS: 2019-nCoV;Adult;Agonist;airway epithelium;Anti-viral Response;Antioxidants;antiviral immunity;Automobile Driving;BACH1 gene;Blood specimen;Cells;cellular pathology;Cessation of life;Child;ChIP-seq;Chromosome 21;Clinical;Cytometry;Development;diagnostic tool;Down's Syndrome;Epithelial Cells;Equilibrium;Exclusion;Exhibits;Exposure to;Foundations;Functional disorder;Gene Expression;Genetic Transcription;Health;high risk;Hospitalization;Human;Immune;Immune response;improved;in vivo;inhibitor;injured airway;innovation;Innovative Therapy;Interferon Activation;Interferon Receptor;Interferons;Knowledge;Lower Respiratory Tract Infection;Mediating;Molecular;mortality;Nose;novel;novel diagnostics;novel strategies;novel therapeutic intervention;Pathogenesis;precision medicine;Predisposition;prevent;public health relevance;Receptor Gene;Recovery;Research;Respiratory syncytial virus;Respiratory Syncytial Virus Infections;Respiratory Tract Infections;response;Role;Severities;Severity of illness;Signal Transduction;single-cell RNA sequencing;transcription factor;Up-Regulation;Viral;Viral Respiratory Tract Infection;Virus;Virus Diseases;Virus Replication;Vulnerable Populations

PROJECT_TITLE: Molecular mechanism of dysregulated airway antiviral responses in children with Trisomy 21

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


ORG_CITY: CHICAGO

ORG_NAME: LURIE CHILDREN'S HOSPITAL OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative Congenital Central Hypoventilation Syndrome (CCHS) is a rare and complex disease, causing a life-threatening inability to regulate breathing and oxygen levels necessitating life-long ventilatory support, in addition to severe Hirschsprung disease, neural crest tumors, and autonomic co-morbidities. Despite limited treatment options and no cures, recent advances in pharmacology, bio-technology, and understanding of the molecular underpinnings of CCHS have paved the way for clinical trials that could advance treatment and reduce morbidity and mortality for these patients. This project will merge traditionally siloed CCHS data, expertise, resources and cohorts to capture extensive, longitudinal natural history data using rigorously defined protocols, common data elements, and established measures reflecting patient and caregiver voices, enriching knowledge of CCHS, establish measures that best correlate with disease severity, inform therapeutic development, and accelerate progress toward clinical trials.

PI_NAMEs: WEESE-MAYER, DEBRA ELLYN (contact)

PROGRAM_OFFICER_NAME: WEIR, NARGUES

PROJECT_TITLE: Progressing toward clinical trial readiness in CCHS: Natural history study to incorporate patient voice, harmonize clinical and registry data, and standardize assessments


ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE The National Center for Quantitative Biology of Complex Systems develops novel technologies that accelerate the pace and depth of protein, lipid, and metabolite analysis. These molecules, and their interactions, regulate the complex cellular processes underlying many devastating diseases. Specifically, the technologies developed in this Resource are being used to advance our understanding of many human conditions including diabetes, Alzheimer’s disease, cancer, and heart disease, among others.

PI_NAMEs: COON, JOSHUA J (contact)

PROJECT_TERMS: Acceleration;Achievement;Alzheimer's Disease;Automobile Driving;Biological;biological systems;Biology;Biomedical Research;Biomedical Technology;Biotechnology;Calibration;Cell Physiology;Chromatography;Collaborations;Communities;community engagement;Complex;Computer software;Data;design;Development;Diabetes Mellitus;Disease;Ensure;Equipment;Evolution;Gene Expression;Genes;Genome;Genomics;Glean;Goals;Heart Diseases;holistic approach;Human;innovation;insight;interest;Internet;Knowledge;Laboratories;Large-Scale Sequencing;Legal patent;lipidome;Lipids;Malignant Neoplasms;Mass Spectrum Analysis;material transfer agreement;Measurement;Metabolism;metabolome;Mission;Molecular;multiple omics;new technology;novel;Nucleic Acids;Pathogenesis;Physiology;Post-Translational Protein Processing;Process;Proteins;Proteome;Proxy;Publications;Regulation;Reporter;Research Personnel;Research Project Grants;Resources;RNA;Role;Scientist;Shoulder;Speed;success;System;Technology;Technology Transfer;Testing;tool;Training;Training Programs;Transcript;transcriptome;Visit;Work

PROJECT_TITLE: P41 Equipment Supplement

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(40)-R]


ORG_CITY: FULLERTON

ORG_NAME: CALIFORNIA STATE UNIVERSITY FULLERTON

ORG_STATE: CA

PHR: Project Narrative from active award number R16GM149204 There has been little innovation in the development of the new analgesic drugs that target novel mechanisms of action. We will focus on the structure-activity relationship studies, biological evaluation, behavioral testing, and optimization of the new dual inhibitors of soluble epoxide hydrolase and fatty acid amide hydrolase enzymes, to increase the levels of anti-inflammatory and analgesic metabolites in the body. Through in vitro and in vivo studies, we aim to demonstrate that the designed dual inhibitors are effectively inhibiting both aforementioned enzymes simultaneously, are metabolically stable, and can produce pain relief in a rat model of chronic inflammatory pain with the potential to become novel, safe, and effective non-opioid treatments for patients suffering from chronic pain.

PI_NAMEs: PECIC, STEVAN  (contact)

PROGRAM_OFFICER_NAME: CUPIT, PAULINE

PROJECT_TERMS: ABCB1 gene;Absence of pain sensation;Acute inflammatory pain;Administrative Supplement;Adult;Affinity;American;Analgesics;analog;Animals;Anti-Inflammatory Agents;antinociception;Applications Grants;Award;behavior test;benzothiazole;Biological;Biological Assay;blood-brain barrier crossing;blood-brain barrier penetration;Brain;Caco-2 Cells;California;Cells;Chronic inflammatory pain;chronic pain;chronic pain management;daily pain;Data;design;Development;Diagnosis;disability;Dose;drug development;Drug Kinetics;Ensure;Enzymes;Epoxide hydrolase;Evaluation;FAAH inhibitor;fatty acid amide hydrolase;follow-up;Formalin;Foundations;Future;Generations;Grant;Hispanic-serving Institution;Human;Hydrolase;IACUC;improved;in silico;In Vitro;in vivo;Incubated;Inflammation;inhibitor;Injections;innovation;Investigation;Ketoprofen;Lead;Libraries;Ligands;Link;Liver Microsomes;Metabolic;Metabolism;Methodology;microwave electromagnetic radiation;Modeling;multidisciplinary;Mus;nanomolar;new therapeutic target;non-opioid analgesic;Non-Steroidal Anti-Inflammatory Agents;novel;Opioid;Pain;Pain management;pain relief;parent project;Patients;Pharmaceutical Preparations;pharmacophore;Play;programs;Property;Protocols documentation;Pump;Rattus;Reporting;Research;Research Personnel;Resources;Role;Side;small molecule;Structure-Activity Relationship;success;System;Testing;Therapeutic;tool;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Designed Multiple Ligands as Non-opioid Analgesics for Treating Chronic Pain


PHR: Mitosis is the process by which duplicated sister chromosomes are evenly distributed to identical daughter cells, and in cancer cells, improper chromosome segregation during mitosis (e.g., such that chromosomes are unevenly distributed between daughter cells) is widely observed, and has been linked to poor prognosis, including decreased overall survival time and fewer treatment free years. In this study, we will make use of physical principles and advanced microscopy to evaluate the role of controlled forces in ensuring proper chromosome segregation during mitosis, and to dissect the role of microtubule structure in the targeting of microtubule- associated proteins. The results generated from our studies will be applicable both towards better understanding the fundamental biophysics of cell division, and also towards providing mechanistic information to shed light on current cancer therapies.

PI_NAMEs: GARDNER, MELISSA  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TITLE: Gardner Lab MIRA Proposal: Microtubules and Mitosis

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_DEPT: NEUROLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative  The overall goal of this proposal is to elucidate the cellular and molecular mechanisms governing the assembly of motor and sensory circuits required for coordinated movement. Our studies will investigate the role of cell fate determinants in establishing synaptic specificity in spinal circuits, and determine how developmental programs contribute to the emergence of specific motor behaviors. Defining the genetic pathways controlling neuronal diversification and connectivity provides basic insights relevant to the study of diseases and injuries that affect spinal motor circuit function.

PI_NAMEs: DASEN, JEREMY S (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Affect;Architecture;Behavior;Breathing;Cells;comparative;design;Development;Disease;Equilibrium;Family;gene function;Genetic;genetic manipulation;genome-wide;Goals;Homeobox Genes;HOX protein;Injury;insight;Mammals;Methods;Modernization;Molecular;Motor;motor behavior;motor control;Motor Neurons;Movement;Muscle;nerve supply;neural circuit;Neural tube;neuromechanism;Neurons;Organism;Pathway interactions;Peripheral;Play;presynaptic;programs;repaired;Research;Role;Sensory;Shapes;Specific qualifier value;Specificity;Spinal;Spinal Cord;Spinal Degenerative Disorder;Synapses;Therapeutic;transcription factor;Walking;Work

PROJECT_TITLE: Genetic Control of Circuit Assembly in the Vertebrate Spinal Cord - Diversity Supplement


ORG_CITY: AMHERST

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: Project Narrative Tight junctions (TJs) are protein assemblies involved in cell adhesion and intercellular transport of molecules through endothelial and epithelial tissues. While many proteins amass at TJs, two families of membrane proteins predominate TJ assembly, organization, and function. The goals of this research are to establish a fundamental understanding of how these two membrane protein families structurally assemble TJs, to identify how their disassembly contributes to TJ dysfunction, and to apply this knowledge by creating new strategies for tissue-specific treatment of TJ-linked diseases in humans.

PI_NAMEs: VECCHIO, ALEX J. (contact)

PROGRAM_OFFICER_NAME: TAYLOR, VERONICA

PROJECT_TERMS: Alzheimer's Disease;Architecture;Bacterial Toxins;base;Biochemical;Bioinformatics;Biophysics;Blood - brain barrier anatomy;Cell Adhesion;Cell membrane;Cells;Charge;Complex;Cytoskeleton;design;Development;Disabling;Disease;Ear Diseases;Endothelial Cells;Endothelium;Environment;Epidermis;Epithelial Cells;Epithelium;experimental study;Extracellular Space;Eye diseases;Family;Food Poisoning;Functional disorder;Gland;Goals;Hepatitis;Human;Huntington Disease;Individual;Inflammatory Bowel Diseases;insight;Integral Membrane Protein;interdisciplinary approach;Ions;Kidney;Knowledge;Laboratories;Limb structure;Link;macromolecular assembly;Malignant Neoplasms;Membrane;membrane assembly;Membrane Proteins;Modification;Molecular;Molecular Conformation;Molecular Structure;novel therapeutics;Organ;Organism;Parkinson Disease;Pathology;Permeability;programs;Protein Family;Proteins;reconstruction;Research;scaffold;Shapes;Side;skin disorder;small molecule;Stroke;structural biology;Structure;Tight Junctions;Tissues;Transport Process;Vertebrates;wasting

PROJECT_TITLE: Structure and assembly of membrane proteins at tight junctions


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Coronaviruses;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Relevance In all living organisms, a molecular machine called the ribosome synthesizes proteins, and decodes the genetic code of messenger RNA (mRNA) in the process of translation. Some mRNAs are translated orders of magnitude more efficiently than the others for reasons that are poorly understood. Translational control by mRNA structure plays an important role in cancer development, and is critical for the infectivity of human viruses such as immunodeficiency virus (HIV) and SARS-CoV-2, which causes the COVID-19 pandemic. We study how structural signals in mRNA regulate translation. Our studies will provide the basis for future development of antiviral and cancer therapies.

PI_NAMEs: ERMOLENKO, DMITRI  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: 2019-nCoV;3' Untranslated Regions;Address;antiviral drug development;Bacteria;Base Pairing;Biochemical;cancer therapy;Cells;Complex;COVID-19 pandemic;Development;DNA;Eukaryota;Future;Genetic Code;HIV;Human;human disease;immunodeficiency;Laboratories;Malignant Neoplasms;Messenger RNA;Microscopy;Molecular;Molecular Biology;Molecular Machines;Movement;Organism;Physiology;Play;Process;Protein Biosynthesis;Proteins;Ribosomes;Role;Signal Transduction;single molecule;Site;stem;Structure;Translating;Translation Initiation;Translation Process;Translational Regulation;translational study;Translations;Virus

PROJECT_TITLE: Structural Dynamics of Translation


NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Heart Disease;Prevention;Social Determinants of Health;Substance Misuse

ORG_CITY: GREENSBORO

ORG_NAME: NORTH CAROLINA AGRI & TECH ST UNIV

PHR: PROJECT NARRATIVE This proposed study seeks to examine the combined effect of lead (Pb), cadmium (Cd), mercury (Hg), perfluorooctane sulfonic acid (PFOS), and perfluorinated alkylated substances (PFOA) on stress, cardiovascular disease (CVD) risk and CVD mortality. The primary analysis will include: (1) assessing the effects of Pb, Cd, Hg, PFOA, and PFOS exposures on individual and neighborhood stress and (2) determining the effects of Pb, Cd, Hg, PFOA, and PFOS exposures on CVD risk and mortality. This study will help close the gap in knowledge of the effects of multiple environmental pollutants on stress and cardiovascular health and will further our understanding of the role that the social environment and the physical environment pose for potentially serious health risks to individuals.

PI_NAMEs: OBENG-GYASI, EMMANUEL  (contact)

PROGRAM_OFFICER_NAME: BERNAL, FEDERICO

PROJECT_TERMS: Address;Affect;Agriculture;alcohol misuse;allostatic load;Black race;Cadmium;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;Censuses;Chronic;Crime;Data;Data Analytics;design;drug misuse;empowerment;Environmental Epidemiology;Environmental Exposure;Environmental Pollutants;environmental stressor;Exclusion;experience;Exposure to;Goals;Health;Hispanic;Individual;Infrastructure;Institution;Intervention;Knowledge;Lead;Life;Life Cycle Stages;Literature;Measures;Mercury;Modeling;mortality;Neighborhoods;North Carolina;Outcome;perfluorooctane sulfonate;Personal Satisfaction;Physical environment;pollutant;Population;programs;Psychosocial Stress;psychosocial stressors;Research;Research Project Grants;Risk;Role;Social Environment;Stress;student training;Students;Surveys;Techniques;theories;United States;Universities;vector;Violence;Vulnerable Populations

PROJECT_TITLE: Acquiring Lambda Vector: Empowering Optimal Analysis of Multipollutant Mixtures with a Full Tower Quad-GPU Workstation