ADMINISTERING_IC: HD

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

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

PHR: Project Narrative The ability to treat and prevent illness and improve human health requires not only a detailed understanding of the complex interplay of biological systems contributing to disease processes but also the mechanisms underlying the influence of social complexity on biological systems. The systems science approach provides methods uniquely suited to elucidate the mechanisms by which social systems influence health. The proposed research adopts this approach by modeling the short- and long-term effects of social interventions on the multiscale and multilayer networks and their effects on biomarkers of individual health in a well- established nonhuman primate model.

PI_NAMEs: MCCOWAN, BRENDA  (contact)

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TERMS: Acute;Adopted;Adult;Adverse event;Age;age acceleration;aged;Aggressive behavior;Aging;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid beta-Protein;Behavioral;Biological;Biological Markers;biological systems;Biology;Blood - brain barrier anatomy;Buffers;Communities;Complex;Data;dementia risk;Development;Disease;effective intervention;Etiology;experience;Family;Friends;Goals;Grant;Health;Human;Immune;immune function;Immunologics;improved;Incidence;Individual;Inflammaging;Inflammation;Inflammatory;insight;Intervention;late life;Life;Long-Term Effects;Longevity;Longitudinal Studies;Macaca mulatta;Mediator;Methods;middle age;Modeling;Modification;neuroinflammation;nonhuman primate;Outcome;Parents;Pathology;Pattern;Positioning Attribute;pre-clinical;prevent;Process;Public Health;R24;Research;Rhesus;Risk;Risk Factors;Sampling;Science;Shapes;social;social adversity;Social Behavior;Social Environment;Social Hierarchy;social influence;social interventions;social relationships;Social support;System;systemic inflammatory response;tau Proteins;Testing;Time;Work

PROJECT_TITLE: Effects of Altering Social Connectedness on Health (Admin Supplement)

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


ADMINISTERING_IC: DA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Opioid Misuse and Addiction;Opioids;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: LA JOLLA

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

ORG_STATE: CA

PHR: Narrative The present Supplement will investigate the detrimental interactions of drugs of abuse and AD with or without concomitant HIV. To this end we will use iPCS-derived neural cultures to model AD in vitro. Ultimately, the proposed experimental-computational approach will result in a better understanding of the molecular mechanisms that are behind the neurodegeneration in HIV, drug abuse, and AD as well as their interactions and will highlight mechanisms of pathogenesis and candidate new therapeutic targets.

PI_NAMEs: REPUNTE-CANONIGO, VEZ ;SANNA, PIETRO P (contact)

PROGRAM_OFFICER_NAME: WU, DA-YU

PROJECT_TERMS: Address;Administrative Supplement;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid beta-Protein;apolipoprotein E-3;apolipoprotein E-4;Astrocytes;Calcium;cell injury;Cells;Closure by clamp;Cocaine;comorbidity;Dementia;dementia risk;design;Drug abuse;Drug Modelings;drug of abuse;Electrophysiology (science);Experimental Designs;experimental study;Exposure to;Fentanyl;Foundations;Gene Expression;Gene Expression Profile;Gene Expression Profiling;gene regulatory network;Genes;Genetic Determinism;Grant;Heroin;HIV;human induced pluripotent stem cells;Image;Impaired cognition;In Vitro;in vitro Model;induced pluripotent stem cell;Knowledge;Methamphetamine;Microglia;Modeling;Molecular;Morphine;Morphology;Nerve Degeneration;neural;neuroAIDS;Neurons;neuropathology;new therapeutic target;Opioid;opioid abuse;Organoids;Oxycodone;parent grant;Pathogenesis;Pathogenicity;Phenotype;Pilot Projects;programs;Qualifying;Regulator Genes;Research;Research Project Grants;response;Science;single nucleus RNA-sequencing;Stimulant;Substance abuse problem;Systems Biology;Testing;United States National Institutes of Health;Work

PROJECT_TITLE: Modeling drugs of abuse-HIV-AD interactions using iPSC-derived neural cells


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF OSTEOPATHIC MEDICINE

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Building Research Capacity at Institutions with Limited NIH Funding

ORG_CITY: PIKEVILLE

ORG_NAME: UNIVERSITY OF PIKEVILLE

ORG_STATE: KY

PHR: The concept of this program derives from our observations that the involution of the human thymus does not follow linear kinetics and is tailored to each individual. We ask how often we can find a functional thymus in the elderly population and find predictors of the thymic function longevity in the elderly. The preliminary results strongly support our hypothesis that the thymus, or part of the organ, may function into old age. In this research proposal, we aim (1) to meet the research goals specified in three research aims, and (2) to provide the Kentucky College of Osteopathic Medicine students with much-needed exposure to basic biomedical research through this REAP funding mechanism.

PI_NAMEs: SIMM, MALGORZATA  (contact)

PROGRAM_OFFICER_NAME: BAKOS, ALEXIS DIANE

PROJECT_TERMS: Age;age group;aged;Aging;Anatomy;Antibodies;Antigens;Biomedical Research;Cadaver;capsule;Categories;Cause of Death;CD14 gene;CD3 Antigens;CD8B1 gene;Cells;Centenarian;Cessation of life;Characteristics;Classification;college;Data;Diameter;Disease;DNA;Elderly;Elements;end of life;Ensure;Epithelium;Excision;Exposure to;Failure;Fellowship;Funding Mechanisms;Gender;Goals;Grant;Harvest;Height;Human;Human body;human old age (65+);Immigrant;Immune system;Immunohistochemistry;Immunology;Individual;inferential statistics;Kentucky;Kinetics;Learning;Lobe;Longevity;Medical Students;Messenger RNA;Microanatomy;Molecular Biology;Molecular Biology Techniques;MS4A1 gene;Organ;Organ Preservation;Osteopathic Medicine;Output;Phenotype;Population;predictive marker;preservation;primary lymphoid organ;Process;programs;Property;Publishing;Race;recruit;Research;Research Proposals;Sampling;sex;Sorting;Specific qualifier value;Spleen;Splenocyte;Stains;Statistical Data Interpretation;statistics;Structure;student participation;Students;Study Subject;T-Cell Receptor;T-Cell Receptor-Rearrangement Excision DNA Circles;T-Lymphocyte;Techniques;Thick;Thymic Tissue;thymocyte;Thymus Gland;Time;Weight;Work

PROJECT_TITLE: The anatomical and functional study of the thymus - defining the milestones of the thymic aging in the elderly human population

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

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;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: HONOLULU

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF HAWAII AT MANOA

ORG_STATE: HI

PHR: The proposed Center for Pacific Innovations, Knowledge, and Opportunities (PIKO) addresses several issues of central importance to building a robust clinical and translational research (CTR) infrastructure that directly improves the health and wellbeing of indigenous Pacific People (IPP), defined as Native Hawaiians, Other Pacific Islanders, and Filipinos, and other underserved populations. The Center will establish a strong collaborative among three academic institutions and a statewide network of stakeholders, including practice-based and community-based organizations and health care providers; convert basic discoveries into real-world solutions to improve IPP health and reduce IPP health disparities; and increase the number of junior and other investigators, particularly from IPP backgrounds, for CTR careers.

PI_NAMEs: KAHOLOKULA, JOSEPH KEAWE'AIMOKU (contact);PALAFOX, NEAL A.

PROGRAM_OFFICER_NAME: FRINCU, CRINA

PROJECT_TERMS: Acceleration;Address;Adoption;Affect;Asian population;Biometry;Budgets;career;clinical development;Clinical Investigator;Clinical Research;Communication;Communities;community engagement;community organizations;Community Outreach;COVID-19 pandemic;culturally appropriate intervention;Data;Data Science;Death Rate;Development;disorder prevention;Dissemination and Implementation;Doctor of Philosophy;Economically Deprived Population;Economics;efficacy study;Ensure;Environment;Epidemiology;Ethnic Population;Evaluation;evidence base;Face;Filipino;Fostering;Funding;Hawaii;Hawaiian;Health;health care availability;health disparity;health disparity populations;Health Personnel;Health Promotion;Homelessness;Human;Impaired cognition;implementation strategy;improved;Indigenous;innovation;Institution;Institutionalization;Investments;Knowledge;Lead;Left;Life;marginalized community;medically underserved population;Mental Health;Mentors;Native Hawaiian or Other Pacific Islander;operation;Participant;Personal Satisfaction;Persons;physical conditioning;Pilot Projects;Policies;Population;Poverty;programs;racial population;Reduce health disparities;Registries;Research;Research Activity;Research Design;Research Infrastructure;Research Personnel;research study;Resources;Role;Rural;rural area;Science;Sexual and Gender Minorities;social health determinants;socioeconomic disadvantage;socioeconomics;success;symposium;Translational Research;Trust;Underinsured;underserved community;Underserved Population;Unemployment;unhealthy lifestyle;Uninsured;United States;United States National Institutes of Health;Universities;user-friendly;Vulnerable Populations

PROJECT_TITLE: Role of Social CONNECTion in Cognitive Decline in Socioeconomically Disadvantaged Populations (CONNECT)


ORG_CITY: DALLAS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE Proteins are the functional workhorses of cells, and a protein’s function is related to and can be predicted from its structure. There is, however, a large class of proteins that have essential biological roles and yet do not have a defined structure (i.e., they’re disordered) and whose function cannot be predicted. This study will use a novel computational approach to comprehensively classify this enigmatic class of sequences to develop a predictive understanding of their function.

PI_NAMEs: PARKER, MATTHEW W. (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Adopted;Algorithms;Amino Acid Sequence;Amino Acids;Architecture;Binding;Biochemical;Bioinformatics;Biological;Biological Assay;Biological Process;Biology;biophysical techniques;Categories;Cell Physiology;Cells;Cellular Assay;Chromatin;Classification;comparative;Computational algorithm;Data;Desiccation;Development;Disease;disease model;DNA Binding;Drosophila genus;Escherichia coli;Etiology;gaze;Genes;globular protein;In Vitro;in vivo;insight;Libraries;Life;Logic;Modernization;Molecular Conformation;Mutation;Nerve Degeneration;novel;Ontology;Organism;Pathogenicity;protein function;Protein Region;protein structure;Proteins;Proteome;Rationalization;Role;structural biology;Structure;Study models;Testing;three dimensional structure;Veins;Work

PROJECT_TITLE: Defining the modular architecture of protein intrinsically disordered regions for a predictive understanding of biological function

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: The proposed CDA-2 will provide Dr. Loflin with the training and data to advance research aimed at improving mental health care among Veterans. The proposed study will include a novel RCT to investigate the efficacy of PE+CBD compared to PE+placebo using a sample of 136 Veterans with PTSD. This will be the first study to test a cannabinoid therapeutic for PTSD within VA. Results from this study will directly inform patient care among Veterans with PTSD, and will be used to inform development of future clinical trial and implementation studies that seek to improve the lives and functioning of Veterans.

PI_NAMEs: AYERS, CATHERINE  (contact)

PROJECT_TERMS: Address;Aftercare;Anxiety;Area;Behavioral;Biometry;Cannabidiol;cannabinoid administration;cannabinoid treatment;Cannabinoids;Caring;Clinic;Clinical;clinical implementation;clinical practice;Clinical Research;Clinical Trials;clinically significant;Cognition;Combination Medication;cost;Data;design;Development;Distress;Double-Blind Method;Dropout;Educational Status;Effectiveness;efficacious treatment;efficacy evaluation;efficacy testing;Exposure to;Extinction;Female;follow-up;Future;future implementation;Goals;Grant;Impairment;implementation study;improved;innovation;Institution;interest;Lead;learning extinction;male;Mediating;Mediation;medical schools;Mental Depression;Mental Health Services;Mentors;Mentorship;military veteran;Mission;Moods;Neurobiology;novel;Participant;Patient Care;Patients;Pharmacotherapy;phytocannabinoid;Placebos;Policies;Post-Traumatic Stress Disorders;pre-clinical research;Psychopharmacology;psychosocial;Psychotherapy;Randomized;Randomized, Controlled Trials;reduce symptoms;Research;Research Personnel;response;Sampling;satisfaction;scaffold;Services;skills;sleep quality;Sleeplessness;Speed;Symptoms;Testing;Training;training opportunity;Trauma;treatment comparison;treatment effect;treatment group;Treatment outcome;treatment response;Veterans;Work;Writing

PROJECT_TITLE: Cannabidiol as an Adjunctive to Prolonged Exposure for the Treatment of PTSD

STUDY_SECTION: MHBB

STUDY_SECTION_NAME: Mental Health and Behavioral Science B[MHBB]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

ORG_CITY: Newark

ORG_DEPT: PHARMACOLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Non-familial Parkinson’s disease is thought to arise from a combination of genetic and environmental factors. The experiments proposed here will enhance our understanding of the epigenetic mechanisms underlying the well-documented epidemiological link between exposure to environmental toxicants and risk of Parkinson’s disease.

PI_NAMEs: BERNSTEIN, ALISON  (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: 3-Dimensional;Adult;Affect;alpha synuclein;Biological;Biological Assay;Brain;Candidate Disease Gene;candidate identification;Cell Culture Techniques;cell type;Corpus striatum structure;cytotoxicity;Data;Development;Dieldrin;Disease;Disease susceptibility;DNA Modification Process;DNMT3a;Dopamine;dopaminergic neuron;Environment;Environmental Risk Factor;Epidemiology;epidemiology study;Epigenetic Process;epigenome;Etiology;experimental study;Exposure to;Functional disorder;Funding;Gene Expression;Gene Expression Profile;Genes;Genetic;genome-wide;genomic locus;Goals;HDAC9 gene;High Pressure Liquid Chromatography;Immunohistochemistry;In Situ;In Vitro;in vivo;in vivo Model;Individual;Inherited;Injections;Knowledge;laser capture microdissection;late life;Link;Luciferases;male;Mass Spectrum Analysis;Mediating;Mediator;Methods;Methylation;methylation pattern;Mission;Modeling;Modification;motor behavior;mouse model;Mus;Mutation;National Institute of Environmental Health Sciences;Neurites;Neurons;neurotransmission;nigrostriatal pathway;novel;NR4A2 gene;offspring;organochlorine pesticide;Parkinson Disease;Parkinsonian Disorders;Pathogenesis;Pathologic;Pathway Analysis;Pathway interactions;Periodicity;Persons;pesticide exposure;Phenotype;Play;pre-formed fibril;Predisposition;Presynaptic Terminals;Radioactive;response;Risk;Risk Factors;Role;Scanning;Sequencing By Hybridizations;sex;Site-Directed Mutagenesis;Specificity;sporadic Parkinson's Disease;synaptic function;synucleinopathy;System;Testing;tool;Toxic effect;Toxic Environmental Substances;toxicant;transcriptome sequencing;uptake;Western Blotting

PROJECT_TITLE: Dieldrin-induced differential gene methylation and parkinsonian toxicity (R01ES031237)


NIH_SPENDING_CATS: Genetics

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Ribonucleic acid (RNA)-protein complexes are integral for every step of gene regulation in the cell, and noncoding RNA-protein complexes especially represent a large unexplored landscape of novel biology and potential therapeutic targets. We have a limited understanding of the contexts – nucleotide sequence, structure, and interaction networks – that determine how and where proteins assemble on RNAs in the cell, and how these complexes might be targeted by small molecules for therapeutic benefit. This proposal describes multiple technological advances in chemical probing and sequencing that will in the long term create a new encyclopedia of RNA-protein network elements, supporting new fundamental discoveries and highlighting the therapeutic potential of noncoding RNA-protein complexes.

PI_NAMEs: WEIDMANN, CHASE A (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Affinity;Antibodies;Antisense Oligonucleotides;base;Base Sequence;Binding;Binding Proteins;Binding Sites;Bioinformatics;Biology;Biotin;Catalogs;Cell Line;Cells;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Data;Data Set;deep sequencing;design;Development;Disease;Drug Targeting;drug-like compound;Elements;Encyclopedias;Environment;experimental study;Gene Expression Regulation;Genes;Genetic;Goals;Human;human disease;Human Genome;improved;interest;Knowledge;Laboratories;Laboratory Research;Laboratory Study;Libraries;Link;Location;Maps;Measurement;Measures;Medical Research;Medicine;Methods;model building;Modeling;Mutation;novel;Nucleotides;Pathway interactions;Postdoctoral Fellow;Process;protein complex;protein structure;Proteins;Protocols documentation;Research;research and development;Resolution;Ribosomes;RNA;screening;Signal Transduction;Site;small molecule;small molecule therapeutics;Specificity;Streptavidin;Structure;targeted treatment;Technology;Therapeutic;therapeutic development;therapeutic target;Time;tool;Transcript;transcriptome;Untranslated RNA;Work

PROJECT_TITLE: Developing RNP-MaP into a broad-spectrum toolset for discovery, definition, and drug targeting of RNA-protein complexes in live cells

STUDY_SECTION: CBP

STUDY_SECTION_NAME: Chemical Biology and Probes Study Section[CBP]


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: PHILADELPHIA

ORG_NAME: RESEARCH INST OF FOX CHASE CAN CTR

ORG_STATE: PA

PHR: PROJECT NARRATIVE DNA damage arising from oxidative stress promotes multiple human diseases, and the cell’s primary defense against these lesions is the base excision repair (BER) pathway. The overarching goal of this study is to elucidate the molecular mechanisms coupling two key biological tasks in response to oxidative DNA damage at certain G- quadruplex promoter sequences –specifically, BER and the transcriptional activation of genes associated with cancer and other diseases. By elucidating the mechanism of gene activation, the findings of this proposal will provide the details required for rational drug design towards targeting their expression by disrupting the key regulatory protein:DNA interactions.

PI_NAMEs: WHITAKER, AMY MICHELLE (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Base Excision Repairs;Biological;Biological Assay;Cells;Coupled;Coupling;Disease;DNA;DNA Damage;DNA Repair;DNA-Protein Interaction;Drug Design;empowerment;endonuclease;Event;Fluorescence;G-Quartets;Gene Activation;Gene Expression Regulation;Genes;genetic regulatory protein;Genetic Transcription;Genome;Goals;Guanine;Hot Spot;human disease;interdisciplinary approach;Knowledge;Lesion;Malignant Neoplasms;Molecular;N-terminal;novel therapeutics;Oxidation-Reduction;oxidative DNA damage;Oxidative Stress;Pathway interactions;Positioning Attribute;programs;promoter;Promoter Regions;Proteins;repaired;Research;response;Role;Scientist;single molecule;structural biology;Techniques;Transcriptional Activation;Transcriptional Regulation

PROJECT_TITLE: Interplay between DNA base excision repair and transcriptional regulation

STUDY_SECTION: MRAA

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: BALTIMORE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Blood flow is essential for ensuring that brain cells have enough energy to fulfill their functions and this energy is extracted from the sugar and the oxygen carried in the blood. Here, we reveal an important novel aspect of an electrical signaling mechanism that brain pericytes (cells that sit on the smallest blood vessels - capillaries) use to precisely match blood flow to local brain energy needs. Through this work we will uncover the unique interactions of ion channels and signaling proteins that constitute this mechanism, which we call the “pericyte chloride clamp”, and thus completing these studies may help to identify novel drug targets on pericytes for therapies that aim to protect or restore blood flow in brain disorders with a blood flow component, such as Alzheimer’s disease and other neurodegenerative conditions.

PI_NAMEs: LONGDEN, THOMAS A (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Alzheimer's Disease;Alzheimer's disease related dementia;Anions;arteriole;Astrocytes;Automobile Driving;biophysical properties;Biosensor;Blood;Blood capillaries;Blood flow;Blood Vessels;Brain;brain cell;brain control;Brain Diseases;brain health;brain pericytes;Brain region;Calcium;Calcium Channel;Calcium Signaling;capillary bed;Capillary Endothelial Cell;Cells;cerebral capillary;cerebral hemodynamics;Cerebrovascular Circulation;Chloride Channels;Chlorides;Closure by clamp;Contracts;Data;Diameter;Dimensions;Disease Progression;Diving;Electrophysiology (science);Endoplasmic Reticulum;Endothelium;Ensure;Event;experimental study;Glucose;Glutamates;hemodynamics;Image;improved;in vivo;in vivo calcium imaging;Ion Channel;Knockout Mice;Knowledge;Laser Scanning Microscopy;Measures;Membrane;Membrane Potentials;Metabotropic Glutamate Receptors;Mus;Nerve Degeneration;Neurons;neurotransmission;new therapeutic target;novel;Optics;optogenetics;Oxygen;P-Q type voltage-dependent calcium channel;patch clamp;Pathologic;Penetration;Pericytes;Pharmacology;Play;Population;Process;Relaxation;Role;Shapes;Signal Pathway;Signal Transduction;Signaling Protein;Smooth Muscle Myocytes;sugar;targeted treatment;Techniques;Therapeutic Intervention;Thinness;Time;tool;two-photon;vascular factor;Work

PROJECT_TITLE: A pericyte Cl- clamp controls capillary electrical signaling and brain blood flow

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


ORG_CITY: CHAPEL HILL

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative The three-dimensional folding of the genome is crucial for the regulation of gene expression. Dysregulations in genome folding have been linked to various diseases, including cancer and developmental disorders. The objective of my proposal is to elucidate the regulatory mechanism of genome folding in living cells, enhancing our understanding of its role in health and disease.

PI_NAMEs: KIM, WONHO  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: 3-Dimensional;cell type;Cells;cohesin;Complex;Development;developmental disease;Disease;Distant;DNA;Elements;Enhancers;experimental study;Gene Expression;Gene Expression Regulation;Genes;Genome;Genomics;Health;In Vitro;Ligation;Link;Malignant Neoplasms;Mediating;Molecular;molecular imaging;Motor Activity;novel;Nuclear;Organism;Pathogenesis;Physiological;Positioning Attribute;Post-Translational Protein Processing;Process;promoter;Regulatory Element;Research;Role;Signal Transduction;single molecule;Techniques

PROJECT_TITLE: Deciphering the Stepwise Regulatory Mechanisms of Genome Folding

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


ORG_CITY: BETHESDA

ORG_NAME: U.S. NATIONAL HEART LUNG AND BLOOD INST

PHR: Project Narrative  Fold-switching proteins challenge the expectation that amino acid sequence dictates only one secondary structure  fold with little understanding of the evolution pathway that made fold-switching prevalent in multiple species downstream of the mutation event. Recent work has identiﬁed fold-switching proteins in human disease, ORF9b in  SARS-CoV-2, but there continues to be a limitation in analyzing fold-switching proteins using techniques that rely  on in vitro techniques. At the completion of this this proposed work I anticipate to not only have an ancestral  reconstruction of the RfaH fold-switching protein, but also structural characterization of mutations to identify  critical residues that support folding dynamics using a new robust and rapid technique, FLIM-FRET.

PI_NAMEs: RONISH, LESLIE  (contact)

PROGRAM_OFFICER_NAME: NELSON, SHAKIRA M

PROJECT_TERMS: 2019-nCoV;3-Dimensional;Accidents;Adopted;alpha helix;Alternative Splicing;Amino Acid Sequence;Amino Acids;beta barrel;Binding;Bioinformatics;Biological Assay;Biophysics;C-terminal;Cell Physiology;Circular Dichroism;Computer software;Confocal Microscopy;Cryoelectron Microscopy;Data;design;Development;Diagnosis;Dissociation;driving force;Escherichia coli;Event;Evolution;expectation;experimental study;Family;Fluorescence;Fluorescence Resonance Energy Transfer;Fostering;Frequencies;Genome;Homologous Gene;Hour;Human;human disease;Human Genome;Hydrogen Bonding;In Situ;In Vitro;Induced Mutation;insertion/deletion mutation;interest;Length;Measures;Medical;Methods;Microscopy;Molecular Conformation;Mutate;Mutation;Mutation Analysis;N-terminal;Nature;NMR Spectroscopy;Organism;pathogen;Pathway interactions;Phylogenetic Analysis;Property;protein complex;protein folding;protein purification;Protein Splicing;protein structure;protein structure prediction;Proteins;rapid technique;reconstruction;Resolution;rho;Ribosomes;RNA Splicing;Screening procedure;Sequence Alignment;Sequence Analysis;Signal Transduction;Site-Directed Mutagenesis;Solubility;statistics;Structure;targeted treatment;Techniques;Tertiary Protein Structure;tool;Translations;Trees;Variant;virulence gene;Work;X-Ray Crystallography

PROJECT_TITLE: Characterization of RfaH evolution and folding dynamics: pairing in vitro and in situ methods

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 TWD-B (MK)]


ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: NARRATIVE This competing renewal requests continued support for the U19 “Center without Walls” entitled “Center Without Walls for Imaging Proteinopathies with PET”. This Center consists of the scientific integration of individuals with an international reputation in the fields of neurobiology, neurology, medicinal chemistry, PET radiochemistry and CNS PET imaging studies towards the common goal of developing PET radiotracers for imaging aggregated alpha synuclein and 4R tau, and investigating their role in neurodegenerative disorders such as Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Frontotemporal Dementia. The scientific resources created by the funding of this U19 Center has led to the first application of the use of ultrahigh throughput screening of large in silico compound libraries in PET radiotracer development. Two radiotracers for imaging alpha synuclein in MSA and PD have been translated to date to the Clinical Core; a third radiotracer for 4R tau is anticipated in year 5 of the current application. The radiotracers developed by this U19 Center are expected to have an important impact on the scientific mission of the National Institute on Neurological Disorders and Stroke (NINDS) in the study of the synucleinopathies and 4R tauopathies.

PI_NAMEs: MACH, ROBERT H (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Acceleration;alpha synuclein;Alzheimer's disease related dementia;Applications Grants;Basic Science;Biology;Brain;brain tissue;California;Central Nervous System Diseases;Chemicals;Chemistry;Clinical;Clinical Investigator;Clinical Research;Collaborations;Communication;Consensus;corticobasal degeneration;Development;Diagnosis;dosimetry;Faculty;first-in-human;Fostering;frontotemporal degeneration;Frontotemporal Dementia;Funding;Funding Mechanisms;Goals;high throughput screening;Histologic;Image;image reconstruction;image translation;Imaging Device;imaging facilities;Imaging ligands;imaging study;Imaging technology;in silico;in vitro Assay;Individual;innovation;Institution;instrumentation;interest;International;Investigational Drugs;Knowledge;Lead;Lewy Body Dementia;Libraries;Ligands;meetings;member;Methods;Mission;multidisciplinary;Multiple System Atrophy;Names;Nervous System Disorder;Neurobiology;Neurodegenerative Disorders;Neurology;novel;Parkinson Disease;Participant;Pennsylvania;Performance;Pharmaceutical Chemistry;Positron-Emission Tomography;professor;programs;Progressive Supranuclear Palsy;protein aggregation;Radiochemistry;Radiology Specialty;radiotracer;Research;Research Personnel;Research Project Grants;Resolution;Resources;response;Role;San Francisco;Series;Site;Stroke;structural biology;Structure-Activity Relationship;synucleinopathy;tau aggregation;tau Proteins;Tauopathies;Translating;United States National Institutes of Health;Universities;Validation;validation studies;Washington

PROJECT_TITLE: Center without Walls for Imaging Proteinopathies with PET

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-N (26)]


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

PROJECT_TERMS: Achievement;Basic Science;Clinical;clinical imaging;Collaborations;Communication;Development;Doctor of Philosophy;Documentation;Ensure;first-in-human;Funding;Goals;Image;image translation;in silico;In Vitro;Individual;Infrastructure;Institutional Review Boards;Investigational Drugs;Maintenance;meetings;member;Mission;molecular imaging;Monitor;National Institute of Neurological Disorders and Stroke;operation;Participant;Patient Recruitments;Pharmaceutical Chemistry;Philadelphia;Positron-Emission Tomography;programs;Protein Biochemistry;Protocols documentation;Radiation;Radiochemistry;radiotracer;Research;Research Personnel;Research Project Grants;Resources;Schedule;screening;Site;structural biology;Teleconferences;Translations;Update;Validation;Writing

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences;Orphan Drug;Parkinson's Disease;Rare Diseases

PROJECT_TERMS: Affinity;alpha synuclein;Amides;Amyloid;Amyloid beta-Protein;analog;Animal Experiments;Autopsy;Autoradiography;Benzamides;Binding;Binding Sites;Biological Assay;Biology;Brain;Chemicals;Clinical;Collaborations;Computer Models;corticobasal degeneration;Cryoelectron Microscopy;Data;design;Development;Disease;Evaluation;Feedback;first-in-human;Fluorescent Probes;Frontotemporal Dementia;High Pressure Liquid Chromatography;high throughput screening;Human;Hydrolysis;Image;imaging study;improved;in silico;in vivo;in vivo evaluation;Indazoles;Individual;Indoles;Institution;Lead;Ligands;Machine Learning;Mass Spectrum Analysis;member;Metabolic;Metabolism;Methods;Modeling;Modification;molecular dynamics;multidisciplinary;Multiple System Atrophy;National Institute of Neurological Disorders and Stroke;nonhuman primate;Parkinson Disease;Patients;Pennsylvania;Pharmaceutical Chemistry;Positron-Emission Tomography;Progressive Supranuclear Palsy;Property;Protein Chemistry;Proteomics;Radiochemistry;Radiolabeled;radioligand;radiotracer;Research;Research Personnel;Research Project Grants;Resolution;Rodent;Route;Sampling;scaffold;Site;solid state nuclear magnetic resonance;Specificity;structural biology;Structure;synucleinopathy;tau aggregation;tau Proteins;Tauopathies;Testing;Tissue Sample;Tissues;Tracer;Universities;Washington

PROJECT_TITLE: Medicinal Chemistry and Radiochemistry Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences;Parkinson's Disease;Rare Diseases

PI_NAMEs: PERLMUTTER, JOEL SYNES (contact)

PROJECT_TERMS: alpha synuclein;Amyloid beta-Protein;Area;Autopsy;Autoradiography;Brain Pathology;California;Clinical;Clinical Data;clinical diagnosis;Clinical Investigator;Clinical Trials Design;cohort;Consensus;Data;Data Collection;data management;data sharing;Data Storage and Retrieval;Development;Devices;Diagnosis;Diagnostic;Disease;dosimetry;Evaluation;Exclusion Criteria;experience;first-in-human;Freezing;Frontotemporal Dementia;Genes;Human;human imaging;Idiopathic Parkinson Disease;Image;Infrastructure;Institution;Institutional Review Boards;International;Investigation;kinetic model;Kinetics;Letters;Longitudinal cohort;Magnetic Resonance Imaging;method development;Movement Disorders;Multicenter Studies;Multicenter Trials;Multiple System Atrophy;Neurodegenerative Disorders;Online Systems;Parkinson Disease;Parkinsonian Disorders;Participant;Patients;Pennsylvania;Pharmaceutical Chemistry;Planet Mars;Positron-Emission Tomography;pre-clinical;Process;Progressive Supranuclear Palsy;Protocols documentation;Radiochemistry;Radiopharmaceuticals;radiotracer;Research Personnel;Resolution;Role;San Francisco;Scheme;Site;Standardization;Structure;symposium;synucleinopathy;tau mutation;tau Proteins;Tauopathies;Tissues;Tracer;Universities;Validation;Washington;web-based tool;Work

PROJECT_TITLE: Clinical Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Dementia;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease

PROJECT_TERMS: Affinity;alpha synuclein;Amyloid beta-Protein;Antibodies;Area;Ataxia;Autonomic Dysfunction;Autopsy;Autoradiography;Binding;Binding Sites;Biological Assay;blood-brain barrier crossing;Brain;brain control;candidate selection;Cells;Clinical;Communication;computational chemistry;Cytoplasm;Cytoplasmic Inclusion;Dementia with Lewy Bodies;Deposition;Development;diagnostic accuracy;Disease;Disease Progression;dominant genetic mutation;Drug Kinetics;efficacy evaluation;Family;Generations;Genes;Goals;high throughput screening;Human;Image;image translation;imaging agent;imaging study;immunohistochemical markers;improved;in silico;In Vitro;in vivo;Individual;Kinetics;Label;Lead;Levodopa;Lewy Bodies;Lewy neurites;Ligands;Measurement;Measures;meetings;member;metabolic abnormality assessment;Methods;microPET;monomer;mouse model;Movement Disorders;Multiple System Atrophy;Mus;Neocortex;Nerve Degeneration;Neurodegenerative Disorders;Neurons;nonhuman primate;Parkinson Disease;Parkinson's Dementia;Parkinsonian Disorders;Pathogenesis;Pharmaceutical Chemistry;Plasma;Positron-Emission Tomography;prevent;Property;protein aggregation;protein TDP-43;Proteins;Radiochemistry;Radiolabeled;radioligand;radiotracer;Research;Role;Sampling;screening;Series;Specificity;Structure-Activity Relationship;Symptoms;synucleinopathy;tau Proteins;Teleconferences;Therapeutic;Tissues;Transgenic Mice;Universities;uptake

PROJECT_TITLE: In Vitro and In Vivo Characterization of Alpha-Synuclein PET Radiotracers


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

PI_NAMEs: MATHIS, CHESTER A (contact)

PROJECT_TERMS: Affinity;Alzheimer's Disease;Alzheimer's disease therapy;Amyloid beta-Protein;analog;Animals;Applications Grants;Autopsy;Autoradiography;Binding;Binding Proteins;Binding Sites;Biochemical;Biodistribution;Biological Assay;Brain;brain tissue;candidate identification;Chemistry;Clinical;Clinical Trials;computing resources;corticobasal degeneration;density;Derivation procedure;Development;Disease;Drug Kinetics;efficacy evaluation;Evaluation;experimental study;Feedback;first-in-human;Frontotemporal Lobar Degenerations;Goals;Grant;high throughput screening;Human;Image;imaging agent;Imaging Device;imaging properties;imaging study;improved;in silico;In Vitro;in vitro testing;in vivo;Indazoles;Indoles;Lead;lead series;meetings;Metabolic;Methods;Microtubules;Molecular;Mutation;Natural History;nonhuman primate;novel;Pathologic;Pathology;Patients;Pharmaceutical Chemistry;Positron-Emission Tomography;preclinical study;Progressive Supranuclear Palsy;Property;Radiochemistry;radioligand;Radiopharmaceuticals;radiotracer;Recommendation;Reporting;Research;Resources;response;Rodent;Rodent Control;Rodent Model;scaffold;Sensitivity and Specificity;Series;Signal Transduction;Source;Specimen;Structure-Activity Relationship;targeted treatment;tau aggregation;tau interaction;tau Proteins;Tauopathies;Testing;Therapeutic;Therapeutic Agents;Tissue Sample;Tissues;Transgenic Organisms;Treatment Efficacy;Variant;Wild Type Mouse;Work

PROJECT_TITLE: In Vitro and In Vivo Characterization of PET Radiotracers for the 4R Variant of Tau


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Schizophrenia;Serious Mental Illness

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Public Health Significance Understanding the alterations in neuropil and connectivity pattern in multiple layers of networks involving structural covariance, white matter and functional connectomes is critical to elucidate adolescent brain maturation. Alterations in these processe may elucidate potential mechanisms underlying nearly 50% of psychiatric illnesses beginning during adolescence which are increasing in the last 2 decades especially among adolescents from lower socioeconomic status (SES) with its adverse consequences on school performance, family relationships, substance use and criminal justice system. This is more onerous for persons who have a first-degree relative with schizophrenia where our proposal could highlight neural pathways as targets for developing new treatment approaches and develop better predictive models to potentially mitigate the risk and develop preventative efforts.

PI_NAMEs: PRASAD, KONASALE M (contact)

PROGRAM_OFFICER_NAME: PACHECO, JENNIFER LYNN

PROJECT_TERMS: 14 year old;18 year old;3-Dimensional;Acceleration;Adolescence;Adolescent;Adult;adverse outcome;Age;Axon;Biochemistry;Biology;Brain;brain tissue;Cells;Childhood;Clinical;Cognitive;cognitive function;cohort;connectome;Criminal Justice;Data;Dendrites;density;design;Development;Diagnosis;Diffusion;Diffusion Magnetic Resonance Imaging;Dimensions;Disease;early adolescence;Enrollment;Ensure;Family Relationship;First Degree Relative;follow-up;Frequencies;Functional Magnetic Resonance Imaging;Goals;gray matter;Growth;high risk;Image;Impairment;improved;in vivo;indexing;Individual;innovation;Interneurons;Literature;low socioeconomic status;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Measures;Mental disorders;Modality;Modeling;Morbidity - disease rate;Nature;Neural Pathways;Neurites;neurobiological mechanism;Neuroglia;neuroimaging;Neuropil;novel;novel therapeutic intervention;Outcome;outcome prediction;Pathology;Pathway Analysis;Pattern;Performance;Persons;Phenotype;Phosphorus;predictive modeling;preservation;Process;Proxy;Psychopathology;Psychoses;Puberty;Public Health;recruit;Research Domain Criteria;Resolution;Rest;Risk;risk mitigation;Schizoaffective Disorders;Schizophrenia;schizophrenia risk;Schools;Severities;social deficits;Social Functioning;Specificity;Structure;substance use;Synapses;System;therapy development;Thick;transition to adulthood;ultra high resolution;white matter

PROJECT_TITLE: Adolescent brain maturation and psychopathology

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Clinical Research

ORG_CITY: PISCATAWAY

ORG_DEPT: BIOMEDICAL ENGINEERING

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

PHR: PROJECT NARRATIVE The long-term goal of this work is to study the structure-function relationship of fibrin(ogen) and its relation to health and disease. To do this, we will probe the structural regulation of key mechanical and enzymatic stability. These fundamental properties of fibrin(ogen) have pathological implications for a variety of diseases and conditions including cancer, thrombosis, pregnancy, and wound healing.

PI_NAMEs: TUTWILER, VALERIE  (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TITLE: MIRA R35: Fibrin(ogen) in regulating health and disease

STUDY_SECTION: MRAD

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Genetics;Regenerative Medicine

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: Project Narrative: A fundamental question for the field of biology is understanding the molecular and cellular mechanisms that regulate tissue regeneration. The proposed research focuses on uncovering the genes and gene regulatory networks operating within cells to facilitate and orchestrate the process of regeneration. This work will expand our understanding of how tissue regeneration is regulated and provide insights for the advancement of regenerative medicine.

PI_NAMEs: WORLEY, MELANIE I. (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Area;Biology;blastema;Cell Reprogramming;Cell Survival;cell type;Cells;Developmental Biology;Dissection;Drosophila genus;Drosophila melanogaster;Event;gene function;gene regulatory network;Genes;Genetic;Genetic Models;Genetic Screening;Genetic Transcription;Goals;in vivo;Individual;insight;Investigation;model organism;Molecular;Natural regeneration;Pattern;Phase;Process;programs;Proliferating;regenerative;regenerative biology;regenerative growth;Regenerative Medicine;Regenerative response;Research;response;single cell technology;support tools;tissue regeneration;Tissues;tumor;tumor growth;tumorigenesis;Work

PROJECT_TITLE: Cellular and Molecular Mechanisms of Regenerative Growth and Repatterning

STUDY_SECTION: MRAC

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


ED_INST_TYPE: OTHER SPECIALIZED SCHOOLS

ORG_CITY: RALEIGH

ORG_DEPT: MISCELLANEOUS

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: PROJECT NARRATIVE This project aims to develop a library of switchable and functional fluorescent probes for multi-functional single-molecule super-resolution imaging of live cells. I will encode distinct single-molecule spectral features of the switchable fluorophores and integrate them with a spectroscopic single-molecule optical imaging platform in the three research thrusts to collectively achieve multi-functional nanoscopic imaging capabilities. This project will allow biomedical researchers, for the first time, to achieve simultaneous interaction imaging of multiple molecules and functional imaging of their surrounding nanoenvironment which fundamentally regulate distinct subcellular processes.

PI_NAMEs: ZHANG, YANG  (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Address;Architecture;Binding;Biochemical;Biology;Biophysics;Cell Physiology;Cells;Cellular biology;Chromatin;chromatin remodeling;chromophore;Complex;complex biological systems;computer studies;design;Development;Dimensions;Engineering;Environment;environmental change;Epigenetic Process;experimental study;Fluorescence;Fluorescent Probes;fluorophore;Functional Imaging;Goals;Higher Order Chromatin Structure;Image;imaging capabilities;imaging platform;Imaging Techniques;Individual;innovation;Label;Libraries;live cell imaging;Maps;Microscopy;Molecular;molecular imaging;multiple omics;nano;nanoenvironment;nanoscale;optical imaging;Optics;Photons;Process;programs;Proteins;Reporting;Research;Research Personnel;Resolution;response;Role;sensor;single molecule;Specificity;Subcellular structure;superresolution imaging;superresolution microscopy;Time;transcription factor;ultra high resolution;Visualization

PROJECT_TITLE: Developing Switchable and Functional Fluorophores For Multi-Functional Super-Resolution Microscopy

STUDY_SECTION: MRAE

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


NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_DEPT: NEUROSCIENCES

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative Dissecting synaptic connectivity is essential for understanding normal brain functions and diseases. However, current available fluorescent sensors that are aimed for detecting synaptic contacts have limitations in in vivo settings. We propose to demonstrate the versatility of a newly developed sensor and apply it to investigate both excitatory and inhibitory connectivity in the context of learning, which will yield valuable resources that contribute significantly to the study of neural circuits.

PI_NAMEs: KWON, HYUNGBAE  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Achievement;Acute;Address;Animal Behavior;Animals;awake;Axon;Biological Process;Brain;cell type;Color;Communication;Complex;Coupled;Dedications;Dendrites;Dendritic Spines;design;detector;Dimerization;Disease;Fluorescence;gamma-Aminobutyric Acid;Goals;Heterodimerization;hippocampal pyramidal neuron;Imaging Techniques;In Vitro;in vivo;in vivo imaging;intercellular communication;Interneurons;Label;Learning;Link;Maps;Methods;Monitor;Names;neural circuit;Neurons;novel;Physiological;Play;Population;postsynaptic;postsynaptic neurons;presynaptic;presynaptic neurons;Process;Property;Proteins;real time monitoring;Reporting;Research;Research Personnel;Resolution;Resources;Role;sensor;sensor technology;Signal Transduction;Slice;Source;Structure;Synapses;Synaptic plasticity;Techniques;Technology;Testing;Time;two-photon;Visualization

PROJECT_TITLE: Real-time mapping of neuronal connectivity at a synapse resolution

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: NARRATIVE: Mitochondrial dysfunction is closely linked to a spectrum of disorders, ranging from primary mitochondrial diseases to age-associated conditions like neurodegenerative diseases. The proposed work here seeks to comprehensively uncover the intricate molecular mechanisms governing the maintenance of mitochondrial homeostasis. These findings hold significant promise for unlocking potential therapeutic avenues to treat diseases associated with mitochondrial dysfunction.

PI_NAMEs: GUO, XIAOYAN  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: age related;attenuation;biological adaptation to stress;Biological Assay;cell type;Cells;Coping Skills;CRISPR screen;Disease;Eukaryotic Cell;Event;fitness;Goals;Homeostasis;Human;Investigation;Link;Maintenance;Mediating;Mitochondria;Mitochondrial Diseases;mitochondrial dysfunction;Molecular;Neurodegenerative Disorders;new therapeutic target;Outcome;Pathologic;Pathway interactions;Phosphorylation;Phosphotransferases;Play;preservation;programs;Protein Biosynthesis;Protein Dynamics;protein transport;Proteomics;reconstitution;Reporter;Research;response;Role;Signal Transduction;Source;Stress;Therapeutic;therapeutic target;transcription factor;transmission process;Work

PROJECT_TITLE: Mechanistic Elucidation of Mitochondrial Stress Response in Human Cells


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Estrogen;Genetics;Human Genome;Orphan Drug;Precision Medicine;Rare Diseases;Women's Health Research

ORG_DEPT: SURGERY

PHR: PROJECT NARRATIVE Male breast cancer has been critically understudied leading to a lack of knowledge of how treatments work in male patients. We will utilize samples from our ongoing ETHAN clinical trial comparing efficacy of endocrine therapy regimens in breast cancer to understand why certain therapies work and why certain tumors respond. In this proposal, we will investigate molecular determinants of response and resistance in men with breast cancer to generate biomarkers of response and identify therapeutic targets to improve response rates.

PI_NAMEs: LEONE, JOSE P.;SPANHEIMER, PHILIP M (contact)

PROGRAM_OFFICER_NAME: BERA, TAPAN K

PROJECT_TERMS: Address;Aftercare;anastrozole;Automobile Driving;Binding;Biological;Biological Markers;Biology;Biopsy;Breast Cancer Patient;Cancer Burden;cancer cell;CDK4 gene;cell type;Cells;Characteristics;ChIP-seq;Clinical Trials;clinically relevant;cohort;comparative efficacy;Copy Number Polymorphism;Counseling;Data;design;differential expression;Endocrine;ERBB2 gene;ESR1 gene;Estrogen Receptors;Estrogens;Excision;Exclusion;experience;Experimental Models;Female;Gene Expression;Gene Expression Profile;Genes;genetic signature;Goals;Heterogeneity;hormone therapy;Hormones;improved;improved outcome;in vitro Model;indexing;Infrastructure;inhibitor;insight;knock-down;Knowledge;Learning;male;Male mammary gland;Malignant Breast Neoplasm;Malignant neoplasm of male breast;Mammary Neoplasms;Measures;men;Molecular;Neoadjuvant Therapy;neoplastic cell;Nuclear RNA;Operative Surgical Procedures;Organoids;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phenotype;Population;pre-clinical assessment;preclinical efficacy;predicting response;Progesterone Receptors;promoter;prospective;Randomized;Rare Diseases;Receptor Gene;Regimen;Residual Cancers;Resistance;Resources;responders and non-responders;response;response biomarker;Sampling;Signal Pathway;single cell sequencing;Specimen;Tamoxifen;targeted treatment;Testing;therapeutic evaluation;therapeutic target;Tissue Procurements;transcriptome sequencing;translational potential;translational study;Treatment Protocols;treatment response;tumor;Woman;women patients;Women's study;Work

PROJECT_TITLE: Predicting Endocrine Therapy Response In Male Breast Tumors

STUDY_SECTION: MCTB

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics B Study Section[MCTB]


ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: NARRATIVE This project addresses fundamental questions about the genetic, molecular, and evolutionary mechanisms underlying changes in gene regulation. Gene regulation is a fundamental process that underlies human health, and how regulation evolves is a key determinant of how it can break down and contribute to disease. A better understanding of the causes and consequences of regulatory change will improve our ability to predict the effects of genetic variation on health and disease.

PI_NAMEs: METZGER, BRIAN PATRICK HANSEN (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TITLE: The genetic and evolutionary mechanisms underlying the origins of new molecularfunctions

STUDY_SECTION: MRAF

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - F Study Section[MRAF]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention;Substance Misuse;Telehealth

ORG_CITY: MADISON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Digital therapeutics for alcohol use disorder are modestly effective but their benefits may be constrained because engagement is often not sustained or matched to patients’ needs. “Smart” digital therapeutics that are enhanced by personal sensing and embedded machine learning lapse prediction models that provide individualized, temporally-precise, risk-relevant information to patients may address these limitations. Our broad goal is to develop a machine learning guided engagement message system that can be added to any smart digital therapeutic to increase risk-relevant engagement and improve clinical outcomes.

PI_NAMEs: CURTIN, JOHN J. (contact)

PROGRAM_OFFICER_NAME: WHITAKER, DAMIYA EVE

PROJECT_TERMS: Address;Adult;alcohol intervention;alcohol use disorder;Back;Behavior monitoring;Behavioral;Clinical;clinical application;Complex;digital measure;digital treatment;drinking;experimental study;Feedback;Frequencies;Future;Goals;Grant;health disparity;Heavy Drinking;Hour;improved;Individual;Influentials;insight;Interpersonal Relations;Intervention;Learning;Life Style;Machine Learning;machine learning model;machine learning prediction;marginalization;Medical;Mental disorders;Mental Health;Modeling;Monitor;multiphase optimization strategy;Nature;Nonlinear Dynamics;Outcome;Output;Participant;Patients;Perception;Performance;Persons;Play;Positioning Attribute;predictive modeling;prevent;Probability;Process;Recommendation;Recovery;Relapse;relapse prevention;Research;Risk;Risk Factors;Role;Sensitivity and Specificity;smartphone application;System;Testing;Therapeutic Uses;Time;Trust;Underserved Population;Update;Variant

PROJECT_TITLE: Optimizing Smart Digital Therapeutic Message Components for Engagement and Clinical Outcomes for Alcohol Use Disorder

STUDY_SECTION: IPTA

STUDY_SECTION_NAME: Interventions to Prevent and Treat Addictions Study Section[IPTA]


PHR: PROJECT NARRATIVE The mammalian innate immune system is essential for host survival, and dysregulation is associated with many human diseases. Activation of the innate immune system is mediated by multiprotein signaling complexes called inflammasomes, but the mechanism of how inflammasomes assemble are not well understood. The goal of this proposal is to systematically map out the assembly of inflammasomes in space and time, which will yield unprecedented mechanistic insights about human immunology that may help develop new treatments for inflammatory diseases and also provide a blueprint for studying other multiprotein signaling pathways.

PI_NAMEs: TAABAZUING, CORNELIUS  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Adaptive Immune System;Adaptor Signaling Protein;Address;Autoimmune Diseases;autoinflammatory diseases;Biology;Biomedical Research;CASP1 gene;Caspase;Cell Death;cell type;Complex;cytokine;Cytokine Activation;Development;Disease;Ensure;Family;Germ Lines;Goals;Homeostasis;Human;human disease;IL18 gene;Immune;Immune system;Immunology;immunoregulation;Inflammasome;Inflammation;Inflammatory;Innate Immune System;insight;Interleukins;Invaded;Lytic;Maps;Mediating;Molecular;Natural Immunity;pathogen;Pattern recognition receptor;Play;Proteins;recruit;Regulation;response;Role;Signal Pathway;Signal Transduction;Signaling Protein;spatiotemporal;therapeutic development;Time;tool;VDAC1 gene

PROJECT_TITLE: Dissecting the molecular mechanism of cytokine activation and spatiotemporal regulation of innate immunity


ADMINISTERING_IC: HS

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: PROJECT NARRATIVE Administrative burdens—the compliance, learning, and psychological costs people face when interacting with and applying for government services—are a key barrier to obtaining health insurance for the over 11 million uninsured Americans that are eligible for subsidized coverage in the Health Insurance Marketplaces created by the Affordable Care Act, as well as millions of Americans that lost Medicaid coverage at the end of the Public Health Emergency and are now eligible to enroll in subsidized Marketplace coverage. This project will use com- plementary quantitative and qualitative research methods from economics, public administration, and anthro- pology to: (1) determine whether premium payment-related compliance costs affects reenrollment in Market- place coverage; (2) determine whether reducing the burden of information costs through advertising affects Marketplace coverage take-up; and (3) create a person-centered understanding of how compliance, infor- mation, and psychological costs erect barriers to Marketplace coverage. This project is relevant to public health because it will identify policy changes state and federal policymakers could make to increase Marketplace health insurance take-up that are not dependent on federal legislation or significant state budget outlays, thereby providing health insurance coverage, which has been shown to reduce mortality, to the remaining un- insured, who disproportionately consist of AHRQ priority populations.

PI_NAMEs: DRAKE, COLEMAN  (contact)

PROGRAM_OFFICER_NAME: KARACA, ZEYNAL

PROJECT_TITLE: Reducing Uninsurance by Addressing Administrative Burdens in the Health Insurance Marketplaces

STUDY_SECTION: HSVR

STUDY_SECTION_NAME: Healthcare Systems and Values Research[HSVR]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Childhood Obesity;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Pediatric;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: Washington

ORG_DEPT: ADMINISTRATION

ORG_NAME: AMERICAN UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative By 2030 almost half of adults are projected to be obese, with nearly 25% projected to have severe obesity. As relatively little is known about how to reduce the prevalence of obesity, our proposal will provide new evidence on the effects of awards from the CDC’s Division of Nutrition, Physical Activity, and Obesity to state and local health departments, land-grant universities, and community-focused organizations, aimed at promoting healthy eating and physical activity. To study the effects of federal funding for obesity prevention on weight-related health behaviors, the prevalence of obesity, and the incidence of obesity-related chronic conditions, we will leverage variation in which states and counties received these awards, when they received the awards, the size of the awards, and the demographic groups targeted by the awards.

PI_NAMEs: CHURCHILL, BRANDYN F (contact)

PROGRAM_OFFICER_NAME: UNALP-ARIDA, AYNUR

PROJECT_TERMS: Address;Adolescent;Adult;adult obesity;Affect;Age;aged;Area;Atherosclerosis;Authorization documentation;Award;behavior influence;Behavioral Risk Factor Surveillance System;blood pressure elevation;Body Weight;Body Weight decreased;cancer type;Centers for Disease Control and Prevention (U.S.);Cessation of life;Child;Chronic;Classification;Communities;Community Health;Congresses;cost;County;Data;Data Set;Diabetes Mellitus;Dietetics;Epidemic;ethnic health disparity;ethnic minority;Ethnic Origin;Exercise;Focus Groups;Funding;Goals;Government;Grant;Health;Health behavior;Health Food;Healthcare Systems;Healthy Eating;healthy weight;Heart Diseases;improved;Incidence;Individual;insight;Life Expectancy;life span;Malignant Neoplasms;Medical Care Costs;Morbid Obesity;National Health and Nutrition Examination Survey;National Heart, Lung, and Blood Institute;Non-Insulin-Dependent Diabetes Mellitus;novel;nutrition;obese person;Obesity;Obesity Epidemic;obesity in children;obesity prevention;Outcome;Overweight;Patient Self-Report;Physical activity;physical state;Policies;Policy Maker;population health;premature;Prevalence;Program Appropriateness;programs;Public Health;Quasi-experiment;Race;racial health disparity;racial minority;Research;Research Personnel;Research Proposals;Risk;Role;Shapes;Social Desirability;Societies;Testing;Universities;Variant;Vital Statistics;Weight

PROJECT_TITLE: New Evidence on the Role of Federal Funding in Reducing the Prevalence of Obesity

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Orphan Drug;Rare Diseases

ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Narrative The emergence of therapy-resistant disease in acute myeloid leukemia (AML) is a major clinical problem. The overall goal of this project is to better understand the leukemia-initiating cells (LICs) that drive disease progression and to identify novel therapeutic regimens that more effectively target the LIC population. These studies stand to improve the efficacy and safety of current therapeutic regimens and increase overall survival for patients with AML.

PI_NAMEs: JORDAN, CRAIG T. (contact);POLLYEA, DANIEL A

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Animal Model;Azacitidine;BCL2 gene;Biology;Calcium;calcium uniporter;Cell Compartmentation;Characteristics;chemotherapeutic agent;chemotherapy;Clinical;clinical investigation;clinical practice;Clinical Trials;cytotoxic;Data;design;Disease Progression;Disease remission;Disease Resistance;DNA Damage;Dose;Drug resistance;Drug Targeting;Elderly;Evaluation;Event;Genetic;Genotype;Goals;Growth;Hematopoietic stem cells;Heterogeneity;Human;improved;improved outcome;in vivo evaluation;inhibitor;inhibitor therapy;Lethal Dose 50;leukemia initiating cell;Measurable;Measures;Mediating;Metabolic;Metabolism;Mitochondria;mitochondrial metabolism;Mitoxantrone;Modeling;Molecular;nanomolar;Newly Diagnosed;novel therapeutics;optimal treatments;Outcome;Oxidative Phosphorylation;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Phosphorylation Inhibition;Population;pre-clinical;Pre-Clinical Model;Prevalence;Proteomics;Refractory Disease;Regimen;Relapse;Residual Neoplasm;Resistance;response;Role;Safety;Sampling;single-cell RNA sequencing;Study models;System;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;therapy resistant;Toxic effect;transcriptomics;Translating;treatment response;uptake;Xenograft procedure

PROJECT_TITLE: Targeting mitochondrial calcium to eradicate leukemia-initiating cells

STUDY_SECTION: ATA

STUDY_SECTION_NAME:
Advancing Therapeutics A Study Section
[ATA]


ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Project Narrative Hypoxia, oxidants, and metals are environmental stressors that cause cellular death and dysfunction. We have discovered that birds and horses possess an enhanced cellular resistance to these stressors, mediated by novel molecular mechanisms. This proposal will allow us to characterize these adaptations, which could identify novel therapeutic strategies to modulate these pathways when they are disrupted in human diseases.

PI_NAMEs: CASTIGLIONE, GIANNI MARCELLO (contact)

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TERMS: Aging;Animals;Biochemistry;biological adaptation to stress;Biology;Birds;Blindness;Cellular biology;Cessation of life;Chronic;Cytoprotection;Data;environmental stressor;Equus caballus;Fishes;Functional disorder;Genome;Goals;Health;Human;human disease;Hypoxemia;Hypoxia;hypoxia inducible factor 1;improved;Knowledge;Malignant Neoplasms;Mediating;Metals;Molecular;Mus;Natural Selections;novel;novel strategies;novel therapeutic intervention;Oxidants;Oxidative Stress;Pathway interactions;Performance;programs;Proteins;Research;Resistance;response;Reverse engineering;Specialist;stem;Stress;stressor;System;Techniques;Vision;Whales;Work

PROJECT_TITLE: Evolutionary Mechanisms of Enhanced Environmental Stress Resistance


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Clinical Research;Clinical Trials and Supportive Activities;Immunization;Infectious Diseases;Lung;Maternal Health;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Vaccine Related;Women's Health Research

ORG_CITY: Bloomington

ORG_NAME: HEALTHPARTNERS INSTITUTE

ORG_STATE: MN

PHR: PROJECT NARRATIVE To date, there are limited data on the safety of Respiratory Syncytial Virus (RSV) vaccination during pregnancy. The goals of this study are to assess the effect of RSV vaccination during pregnancy on lactation and on newborn and child health. The results of the study will complement ongoing vaccine safety surveillance and will help patients and their clinicians make more informed decisions about RSV vaccination during pregnancy.

PI_NAMEs: PALMSTEN, KRISTIN  (contact)

PROGRAM_OFFICER_NAME: FABIYI, CAMILLE

PROJECT_TERMS: Address;Admission activity;Advisory Committees;Age Months;age related;Allergic;antenatal;Apgar Score;Atopic Dermatitis;Biological;Birth;Breast Feeding;Centers for Disease Control and Prevention (U.S.);Child;Child Health;Clinical;Clinical Trials;Complement;Conduct Clinical Trials;Convulsions;COVID-19 vaccination;Data;data structure;Decision Making;Development;Diagnosis;Electronic Health Record;Epidemiologic Methods;Exclusion;FDA approved;Food;Food Hypersensitivity;Funding;Gestational Age;Goals;Growth;Growth and Development function;Guidelines;Hawaii;Health system;high risk;Hospitalization;IgE;Immunization;Infant;Information Systems;Lactation;Lower respiratory tract structure;Mediating;Mediation;Medical;Methods;Minnesota;Monoclonal Antibodies;Mothers;Neonatal;neonatal health;Neonatal Intensive Care Units;Neonatal Jaundice;neonatal outcome;neurodevelopment;Newborn Infant;newborn wet lung disease;Oregon;Outcome;Patients;Persons;Phase;placebo group;Pneumonia;Population;Positioning Attribute;Postpartum Period;Pregnancy;pregnant;Premature Birth;prenatal;prevent;Probability;Proctocolitis;Proteins;Recommendation;Reporting;Research;Research Design;respiratory distress syndrome;Respiratory syncytial virus;Respiratory Syncytial Virus Infections;Respiratory Syncytial Virus Vaccines;Risk;Safety;screening;Screening Result;Seasons;Selection Bias;Sepsis;Small for Gestational Age Infant;Surveys;Time;United States;United States Food and Drug Administration;United States National Institutes of Health;unvaccinated;uptake;Vaccination;vaccine acceptance;vaccine efficacy;vaccine safety;Vaccinee;Vaccines;volunteer;Washington;Well Child Visits;Wisconsin

PROJECT_TITLE: Neonatal, Lactation, and Child Health Outcomes Following RSV Vaccination During Pregnancy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-M (81)]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Kidney Disease;Precision Medicine

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: PROJECT NARRATIVE Immune checkpoint inhibitor (ICI) therapy leverages the body’s immune system to target cancer, but it can lead to off-target side effects that present as acute interstitial nephritis in the kidneys. There are no non-invasive biomarkers of ICI-induced acute interstitial nephritis, which poses significant diagnostic and therapeutic challenges. We will recruit a longitudinal cohort of 400 participants receiving ICIs who develop acute kidney injury to identify biomarkers and dysregulated pathways in acute tubulointerstitial nephritis to improve diagnosis and treatment response phenotyping.

PI_NAMEs: MOLEDINA, DENNIS G. (contact);SISE, MEGHAN E.

PROGRAM_OFFICER_NAME: SCHULMAN, IVONNE HERNANDEZ

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;Address;adjudication;Adrenal Cortex Hormones;Automobile Driving;Award;biobank;Biological Markers;biomarker discovery;biomarker identification;Biometry;cancer care;cancer type;Caring;CCL1 gene;checkpoint therapy;chemokine;Classification;Clinical;Clinical Trials;cohort;Collaborations;Creatinine;CXCL9 gene;Data;Diagnosis;Diagnostic;diagnostic biomarker;early detection biomarkers;Enrollment;Etiology;experience;FDA approved;follow-up;Future;General Hospitals;Goals;Healthcare;Healthcare Systems;Histologic;Immune checkpoint inhibitor;Immune system;Immune Targeting;immune-related adverse events;Immunoassay;Immunologic Markers;Immunosuppressive Agents;implementation trial;improved;Infiltration;Inflammation;Injury to Kidney;Interferon Type II;interstitial;Interstitial Nephritis;Intervention;Judgment;Kidney;kidney biopsy;lateral flow assay;Life;Ligands;Longitudinal cohort;Malignant Neoplasms;Massachusetts;Measurement;Measures;Monitor;mortality;mRNA Expression;multidisciplinary;Oncology;Organ;Participant;Pathway Analysis;Pathway interactions;Patient Care;Patient-Focused Outcomes;Patients;personalized management;Pharmaceutical Preparations;Phenotype;Plasma;point of care;predicting response;Prediction of Response to Therapy;predictive marker;prospective;Proteins;Proteomics;rapid diagnosis;Recovery;Recovery of Function;recruit;Refractory;renal damage;Renal function;Research;response;response biomarker;Risk;Sampling;Serum;side effect;Site;Steroid therapy;Steroids;Subgroup;T cell response;T-Lymphocyte;Testing;Therapeutic;Therapeutic immunosuppression;Time;Tissues;treatment response;Tubulointerstitial Nephritis;Tumor Antigens;Urine;Validation

PROJECT_TITLE: Rapid Diagnosis and Treatment Response Phenotyping of Immune Checkpoint Inhibitor-Associated Acute Interstitial Nephritis

STUDY_SECTION: KEDD

STUDY_SECTION_NAME: Kidney Endocrine and Digestive Disorders Study Section[KEDD]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Arthritis;Biotechnology;Osteoarthritis;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: ORTHOPEDICS

PHR: Osteoarthritis (OA) is a painful and disabling joint disorder affecting more than 30 million Americans, and none of the current treatments for OA are clinically demonstrated to reverse OA progression. In this application, we propose to use the in vitro models to repurpose FDA-approved drugs for OA treatment through high-throughput screening. The successful completion of this study will generate a potential drug pool that is ready for study in human clinical trials.

PI_NAMEs: BUNNELL, BRUCE A.;GOODMAN, STUART B;LIN, HANG  (contact)

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: Address;Adipose tissue;Affect;aged;aggrecan;American;analog;Animal Model;Animals;arthropathies;B-Cell Activation;Biosensor;bone;Cartilage;cartilage regeneration;Cell Count;Cell Survival;cell type;Cells;Chondrocytes;Clinical;Clinical Trials;clinically relevant;cost efficient;Degenerative polyarthritis;Disabling;Disease;Disease Progression;Dose;Drug Combinations;drug repurposing;drug testing;efficacy testing;Encapsulated;Enhancers;FDA approved;Fibroblasts;Fluorescence;Generations;Green Fluorescent Proteins;Heterogeneity;high throughput screening;Histology;Human;human induced pluripotent stem cells;hydrogel scaffold;Image;Impairment;In Vitro;in vitro Model;in vivo;Inflammation;Inflammatory;Interleukin-1 beta;Joints;Knee joint;Lentivirus Vector;Libraries;Light;Macrophage;mesenchymal stromal cell;microphysiology system;Modeling;Molecular Target;Monitor;monocyte;multipotent cell;National Center for Advancing Translational Sciences;novel;novel therapeutics;Nuclear;Organoids;osteochondral tissue;Pain;pain relief;Patients;personalized approach;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Physiological;preclinical efficacy;preservation;Process;promoter;Reporter;Safety;screening;senescence;Signal Transduction;Stains;stressor;Synovial Membrane;Testing;Therapeutic;Time;Tissue Model;Tissues;Toxic effect;Translating;Variant

PROJECT_TITLE: Repurposing FDA-approved drugs for the treatment of osteoarthritis using high-throughput screening in microphysiological models

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]


NIH_SPENDING_CATS: Brain Disorders;Fragile X Syndrome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: PROJECT NARRATIVE  The proposed work will fill a major gap of our knowledge in understanding function of FMRP in regulating energy metabolism during human brain development. Such understanding is critical for better therapeutic development for fragile X syndrome as well as other neurodevelopmental disorders including autism.

PI_NAMEs: ZHAO, XINYU  (contact)

PROGRAM_OFFICER_NAME: LEE, CRYSTAL ANNE

PROJECT_TERMS: Animal Model;autism spectrum disorder;Behavioral;Biogenesis;Brain;Brain Diseases;Clinical Trials;crosslinking and immunoprecipitation sequencing;Data;Development;Disease;Energy Metabolism;Etiology;Exhibits;Experimental Models;FMR1 gene;Fragile X Syndrome;Gene Expression;Genes;Heritability;Human;Human Development;human pluripotent stem cell;Impairment;Intellectual functioning disability;interest;Knowledge;Leflunomide;Link;Literature;loss of function;Mass Spectrum Analysis;Mediator;messenger ribonucleoprotein;Metabolic;Metabolism;metabolome;Mitochondria;Molecular;mouse development;multiple omics;Mus;Neocortex;neurodevelopment;Neurodevelopmental Disorder;neuron development;Neuronal Differentiation;Neurons;Oxidative Phosphorylation;Paper;Phenocopy;pluripotent stem cell differentiation;prevent;primary endpoint;Process;Proteins;Proteome;Publishing;receptors for activated C kinase;Regulation;response;RNA-Binding Proteins;Rodent;Role;Scaffolding Protein;Stimulus;therapeutic development;transcriptome;Translating;Work

PROJECT_TITLE: FMRP regulation of mitochondria and metabolism in mammalian brain development

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Genetics

PHR: PROJECT NARRATIVE Conflicts between transcription and replication machinery are frequent and the consequences on DNA replication are the subject of many studies. In contrast, the consequences on transcription and gene expression remain essentially unexplored. As accurate regulation of gene expression is crucial for normal development and dysregulation of transcription is a key factor in disease states, this proposal aims to investigate how these conflicts affect transcription and their physiological significance.

PI_NAMEs: BHOWMICK, RAHUL  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Accidents;Affect;Aging;Alternative Splicing;cell type;Cells;circular RNA;Complex;conflict resolution;Dedications;Development;Disease;DNA biosynthesis;DNA Damage;Face;fitness;Future;Gene Expression;Gene Expression Regulation;Genetic Transcription;Genome;Genomic DNA;Genomic Instability;Goals;Homeostasis;Human;Kinetics;Malignant Neoplasms;Oncogene Activation;Pathologic;Pathway interactions;Physiological;Poly A;Polyadenylation;Process;Production;programs;Proliferating;Protein Isoforms;Regulation;Replication Origin;Replication-Associated Process;RNA Polymerase II;Role;small molecule;Speed;Time;Transcript;Transcription Initiation Site;Transcription Process;transcription termination;tumorigenesis;Variant;Work

PROJECT_TITLE: Characterizing the effect of transcription-replication conflicts on transcription and co-transcriptional processes


ORG_CITY: HOUSTON

ORG_DEPT: CHEMISTRY

ORG_NAME: RICE UNIVERSITY

PHR: Project Narrative In this work we will develop advanced cellular labeling and imaging tools to address a range of biophysical questions related to molecular mechanisms behind cellular function, including how the dynamics of chromatin organization affect gene expression and what the molecular mechanisms are that underlie Hutchinson-Gilford Progeria Syndrome (HGPS). HGPS is caused by mutations in the nuclear lamina protein prelamin A. Determining the molecular mechanisms of how mutated prelamin A distributes and interacts with other proteins and DNA and how these mechanisms are affected by available and novel drugs will lay the foundation for advances in disease treatment strategies.

PI_NAMEs: GUSTAVSSON, ANNA KARIN EVA (contact)

PROJECT_TERMS: 3-Dimensional;Address;Affect;aging related disease;Algorithmic Analysis;Binding;biological systems;Biophysics;Cell Nucleus;Cell Physiology;Cells;Chromatin;ciliopathy;Data;design;Detection;Disease;Disease Progression;DNA;Engineering;Enhancers;Environment;extracellular;Fluorescence;Foundations;Frequencies;Gene Expression;Gene Expression Regulation;Genetic Transcription;Goals;Health;Human;Imaging Device;improved;innovation;interest;Kinetics;Label;Light;Lighting;live cell imaging;Malignant Neoplasms;Mammalian Cell;Maps;Measurement;Medical;Methods;Microfluidics;Molecular;Mutate;Mutation;nanobodies;nanometer;nanoscale;novel;novel therapeutics;Nuclear Lamina;Output;Pathogenesis;Photobleaching;prelamin A;Premature aging syndrome;Progeria;promoter;Proteins;Regulatory Element;Research;Resolution;Scheme;single molecule;Spatial Distribution;spatiotemporal;Structure;superresolution imaging;Syndrome;System;treatment strategy;Work

PROJECT_TITLE: Molecular mechanisms in the mammalian cell nucleus

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


ORG_CITY: BINGHAMTON

ORG_NAME: STATE UNIVERSITY OF NY,BINGHAMTON

ORG_STATE: NY

PHR: Project Narrative Addressing the pivotal challenge of re-delivering gene therapy via Adeno-associated viruses (AAVs) due to immune constraints, this research pioneers advanced delivery and targeting strategies across three distinct pharmaceutical platforms to modulate immune responses and enable repeated gene therapy. By overcoming specific biological barriers and controlling adverse immune reactions, this work aspires to significantly advance the safety and efficacy of gene therapies while developing novel delivery platforms for therapeutic cells, enzymes, and vaccines. The realization of this research promises to mitigate illnesses and disabilities associated with genetic disorders, thereby contributing to enhanced public health.

PI_NAMEs: MEI, KUO-CHING  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Address;adeno-associated viral vector;Antibodies;antigen processing;Antigen-Presenting Cells;Antigens;Biological;Biological Response Modifier Therapy;Cell Therapy;cell type;Cells;cellular transduction;chimeric antigen receptor;cytotoxic;delivery vehicle;Dependovirus;disability;Engineering;Ensure;Enzymes;Excision;Formulation;Gene Delivery;Gene Expression;gene therapy;Genes;Genetic Diseases;Health;Human;Immune;Immune response;Immune system;immunogenic;immunogenic cell death;Immunoglobulin G;immunoreaction;immunoregulation;Immunosuppression;improved;in vivo;innovation;Instruction;lipid nanoparticle;Methods;mRNA delivery;neutralizing antibody;novel;Peptide Hydrolases;Pharmacologic Substance;Production;programs;Public Health;Reaction;Regulatory T-Lymphocyte;Research;response;RNA delivery;Safety;siRNA delivery;Site;stem;System;targeted delivery;Therapeutic;Transgenes;Update;Vaccines;vector;viral gene delivery;Work

PROJECT_TITLE: Complementary Biotherapeutic Delivery Platforms for Enabling Gene Re-delivery


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Genetics;Lung;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative: Mast cells (MC) are potent inflammatory cells that dramatically increase in concentration in the lungs of asthmatics and nasal polyps, however the committed progenitor from which they are thought to arise from is one of the rarest cells in circulation. After identifying a series of markers to better identify MC progenitors (MCps) within inflamed airway tissue, we observed that MCp robustly proliferative within inflamed tissue, likely explaining their disproportionate relationship with tissue resident MC concentration. This proposal seeks to better characterize infiltrating MCp in human airway tissue, identify the discrete epithelial- and fibroblast- derived signals responsible for directing MCp proliferation and differentiation, and determining the transcription factor networks that underly the resulting MC phenotypes.

PI_NAMEs: DWYER, DANIEL F (contact)

PROGRAM_OFFICER_NAME: LIU, QIAN

PROJECT_TERMS: Address;Airway Disease;airway epithelium;airway inflammation;Anabolism;Aspirin;Asthma;asthmatic;Automobile Driving;CD34 gene;Cell Differentiation process;Cell Proliferation;Cell surface;Cells;Characteristics;chemokine;chronic rhinosinusitis;Chymase;Circulation;Coculture Techniques;comorbidity;Connective Tissue;CRISPR/Cas technology;cysteinyl-leukotriene;cytokine;Development;differential expression;Disease;Disease Progression;Effector Cell;Eicosanoids;Eosinophilic Esophagitis;Epithelial Cells;Epithelium;Exhibits;experimental study;falls;Family;Fibroblasts;Genes;Genetic Polymorphism;Genetic Transcription;Growth;Histamine;Human;human disease;In Situ;In Vitro;in vivo;Infiltration;Inflammation;Inflammatory;Interleukin-13;Interleukin-5;intraepithelial;knock-down;Ligands;Link;Location;Lung;MADH3 gene;mast cell;mastocytosis;Mediating;Mucous Membrane;Mus;Nasal Polyps;Non-Steroidal Anti-Inflammatory Agents;Nose;novel;novel therapeutic intervention;Nucleotides;Pathway interactions;Peptide Hydrolases;Peripheral;Peripheral Blood Mononuclear Cell;Phenotype;Play;polarized cell;polyposis;Polyps;Population;Process;Production;progenitor;Proliferating;Prostaglandin D2;Publishing;Reaction;recruit;Reporting;Respiration Disorders;respiratory;Respiratory Disease;Respiratory Mucosa;Risk;Role;Series;Severities;Severity of illness;Signal Transduction;Single Nucleotide Polymorphism;small hairpin RNA;stem cell differentiation;stem cell proliferation;stem cells;Stromal Cells;System;Testing;Therapeutic;Time;Tissues;transcription factor;transcriptomics;Transforming Growth Factor beta;Tryptase;WNT Signaling Pathway

PROJECT_TITLE: Determining drivers of mast cell expansion and function during human airway disease

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


ORG_CITY: STORRS-MANSFIELD

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

PHR: Project Narrative The proposed research aims to elucidate the mechanisms and extent of two key processes involved in oral drug absorption, the particle drifting effect and precipitation kinetics, and to provide guidance for the development of oral enabling formulations. The proposed work will develop a combined experimental and modeling framework to achieve model-based formulation development and improved bioavailability prediction. The generated knowledge will greatly decrease drug development costs, reduce the need of animal pharmacokinetic experiments, allow more drugs to enter the market, lessen patients’ financial burden, and ultimately save more patients’ lives.

PI_NAMEs: LI, NA  (contact)

PROJECT_TERMS: absorption;Affect;amorphous solid;Animal Experiments;Animals;aqueous;Area;Biological Availability;commercialization;Complex;cost;design;Development;drug candidate;drug development;drug discovery;Drug Formulations;Drug Kinetics;Excipients;experimental study;Financial Hardship;Formulation;improved;In Vitro;in vivo;insight;kinetic model;Kinetics;Knowledge;Life;Lipids;Lymphatic;Marketing;Modeling;Oral;Outcome;particle;Patients;Permeability;Pharmaceutical Preparations;pharmacokinetic model;Physiological;Positioning Attribute;Precipitation;Process;Property;Research;Resources;Solubility;submicron;Testing;Time;uptake;Work

PROJECT_TITLE: Enabling oral drug formulations: mechanistic studies and modeling


ORG_CITY: UNIVERSITY PARK

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Project Narrative The proposed research aims to develop new synthetic methods that will improve access to critical materials for the discovery and manufacture of medicinal agents. These methods will include (a) olefin difunctionalizations to rapidly convert simple and abundant chemical feedstocks into complex skeletons and pharmacophores, and (b) stereoselective α-functionalizations of carbonyls to generate novel amino acids and medicinal products and intermediates. Owing to their “radical-mediated migration” mechanisms that have significant latent potential, these new approaches will afford clear advances in pharmaceutical synthesis by enabling reactions with improved stereocontrol and a significantly expanded range of medicinally valuable motifs they can access.

PI_NAMEs: NACSA, ERIC D (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Harnessing the Latent Potential of Radical Migration to Drive Synthetic Innovation


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

ORG_CITY: LAWRENCE

ORG_NAME: UNIVERSITY OF KANSAS LAWRENCE

ORG_STATE: KS

PHR: PROJECT NARRATIVE Great Plains and Midwestern states lack scientists with the cross-cutting training to both push forward foundational, biomedical research, and effectively educate the scholars of the future. The IRACDA at the University of Kansas (KU) seeks to address this challenge by providing postdoctoral scholars expertise in research through experiential training with an accomplished KU faculty member. Additionally, our KU-IRACDA scholars will gain instructional experience via collaborations with Haskell Indian Nations University (a tribal college dedicated to educating members of American Indian and Alaska Native communities) and Kansas City Kansas Community College (a 2-year college with a diverse student body), where they will simultaneously act as early career mentors for students from groups underrepresented in the biomedical sciences.

PI_NAMEs: CARTWRIGHT, PAULYN ;MACDONALD, STUART JOHN (contact);NEUFELD, KRISTI L

PROJECT_TERMS: Academia;Advisory Committees;Area;Award;Biomedical Research;Cancer Center;career;Cities;cohort;Communities;community college;Dedications;Development;Development Plans;Educational process of instructing;Educational workshop;Ensure;experience;Faculty;Financial Support;Future;Generations;Goals;Grant;Individual;Institution;Instruction;Kansas;Learning;Life;member;Mentors;Methods;Mission;Modernization;National Institute of General Medical Sciences;next generation;Occupations;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;Preparation;Process;programs;Publications;recruit;Research;Research Infrastructure;Research Personnel;Science;Scientist;Series;skills;Students;success;System;Target Populations;Teaching Method;Time;tool;Training;Training Activity;Universities;Work

PROJECT_TITLE: IRACDA at the University of Kansas

STUDY_SECTION: TWD

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


NIH_SPENDING_CATS: Clinical Research;Microbiome

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Alterations in the human microbiome have been associated with a wide variety of diseases; however, the specific mechanisms that allow microbiota to regulate host health have not been fully elucidated. This work will explore the microbiome’s role in tissue homeostasis by investigating how commensal bacteria degrade ECM, identifying microbial enzymes involved in this process, and understanding the impact of remodeled ECM on innate immune cell behavior. In the long term, these studies will lead to the identification of mechanisms that link human microbiota to ECM dysregulation and inflammation, potentially paving the way towards novel diagnostic and therapeutic approaches.

PI_NAMEs: PORRAS, ANA MARIA (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Address;Award;Bacteria;bacterial metabolism;Biochemical;Biocompatible Materials;Body part;Carbohydrates;cell behavior;Cell Physiology;Cells;commensal bacteria;commensal microbes;Cues;Data;Development;Disease;Environmental Risk Factor;Enzymes;Extracellular Matrix;Extracellular Matrix Degradation;Fibroblasts;Functional disorder;Growth;Health;Homeostasis;Human;Human Microbiome;human microbiota;human tissue;Immune;In Vitro;Incubated;Individual;Inflammation;Inflammatory Bowel Diseases;Knowledge;Light;Link;Macrophage;Maintenance;Malignant neoplasm of cervix uteri;metaproteomics;Microbe;microbial;microbiome;microbiota;microorganism;Modeling;neutrophil;novel diagnostics;novel therapeutic intervention;Nutrient;Peptide Hydrolases;Phenotype;Process;programs;Property;Pulmonary Cystic Fibrosis;Research;Role;Source;Testing;tissue culture;Tissue Engineering;Tissues;Vagina;Vision;Work

PROJECT_TITLE: Microbiota and Extracellular Matrix Interactions that Drive Host Tissue Remodeling

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


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hypertension;Racial and Ethnic Minority Health Research;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Dysregulated aldosterone production from one or both adrenal glands (primary aldosteronism, PA) is the most common cause of endocrine hypertension, accounting for 5-10% of hypertension and 14-20% of resistant hypertension. Research focused on defining the genetic causes of PA in Black Americans is limited despite their high prevalence of hypertension, and the higher susceptibility to hyperaldosteronism and cardiovascular mortality. The central goals of this proposal are to define the spectrum of adrenal aldosterone-driver somatic mutations in Black American PA patients and identify targeted therapeutics that block mutation-driven aldosterone production in endocrine hypertension.

PI_NAMEs: REGE, JUILEE  (contact)

PROGRAM_OFFICER_NAME: PRICE, CANDICE

PROJECT_TERMS: Accounting;Address;adenoma;Adrenal Gland Diseases;Adrenal Glands;adrenal hypertension;Aldosterone;ATP1A1 gene;Bilateral;Black American;black men;Black race;black women;Blood Pressure;Calcium;Calcium Channel;Calcium Signaling;Cardiovascular system;Caring;Cell Line;Cells;Clinical;Consensus;CYP11B2 gene;Data;design;Detection;Development;Diffuse;Disease;DNA;DNA sequencing;driver mutation;East Asian;efficacy evaluation;Essential Hypertension;Etiology;exome sequencing;Formalin;Functional disorder;Future;Gene Mutation;Genes;Genetic;Genetic Engineering;Goals;High Prevalence;Histopathology;Homeostasis;Hyperaldosteronism;Hyperplasia;Hypertension;hypertensive;Immunohistochemistry;improved;inhibitor;inhibitor therapy;inward rectifier potassium channel;L-Type Calcium Channels;Lesion;Medical;Mineralocorticoid Receptor;Molecular;Morbidity - disease rate;mortality;Mutate;Mutation;next generation sequencing;Nodule;novel;Operative Surgical Procedures;Paraffin Embedding;Pathogenesis;Patients;Population;Predisposition;Prevalence;prevent;Production;Proteins;Public Health;racial difference;Receptor Activation;Renin;Research;Resistant Hypertension;salt sensitive hypertension;Series;Sodium;Somatic Mutation;targeted treatment;Technology;Testing;Therapeutic;Tissue Embedding;Tissues;voltage

PROJECT_TITLE: Genetic Causes of Endocrine Hypertension in Black Americans

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: NEW YORK

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Narrative Body development requires precise gene expression in a spatial and temporal manner, which is controlled by epigenetic modifications. We aim to understand how a critical epigenetic mark is regulated to control gene expression. A complete understanding of the regulation program will reveal new cellular or pharmacological strategies for treating genetic disorders with dysregulated gene expression.

PI_NAMEs: LONG, YICHENG  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Cardiac;Cells;chromatin modification;Complex;Data;Deposition;Development;Developmental Gene;Embryo;Enzymes;Epigenetic Process;epigenetic regulation;epigenetic silencing;Gene Expression;gene repression;Genes;Genetic Diseases;genetic manipulation;Genetic Transcription;Genome;Heterochromatin;Histone H3;histone methylation;Human body;human disease;Knowledge;Lysine;Methods;Methylation;Modification;mutant;Mutate;new therapeutic target;Nucleic Acids;pharmacologic;Play;pluripotency;Polycomb;Prevention;Process;programs;Proteins;Regulation;Repression;Series;spatiotemporal;Specific qualifier value;Specificity;Switch Genes;Testing

PROJECT_TITLE: Spatiotemporal regulation of epigenetic silencing by macromolecular interactions

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


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Genetics;Human Genome;Neurosciences

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative Genetic screens, in which mutations are randomly made in a large number of genes in the genome and their phenotypic effect on tissues of interest are assayed, have been a predominant approach for functionally characterizing the roles of genes in development. However, traditional genetic screens are limited because some genes are required for multiple functions, some functions can be accomplished by multiple genes, and because screens are very laborious especially in vertebrates. Here, we leverage recent technological advances in single cell perturbation and measurement along with the “regulative ability” of vertebrates to develop a new type of genetic screen in which cells with different mutations compete within an embryo to form a normal embryo, and use this approach to study the eye.

PI_NAMEs: KLEIN, ALLON MOSHE (contact);MEGASON, SEAN G

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: 3' Untranslated Regions;Animals;Bar Codes;Benchmarking;Biological Assay;capsule;Catalogs;Cataract;cell type;Cells;Cellular biology;Chromium;Classification;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Communities;Complement;cost;cost efficient;CRISPR library;CRISPR/Cas technology;Data;Data Sources;design;Detection;Development;Developmental Biology;developmental genetics;Disease;droplet sequencing;Embryo;Evaluation;Eye;Eye diseases;Fishes;fitness;functional genomics;gene function;Genes;Genetic;Genetic Screening;Genome;genome-wide;Genomics;Genotype;Germ Lines;Glaucoma;Grant;Harvest;Hereditary Disease;Homologous Gene;In Situ;in vivo;Individual;interest;invention;Knock-out;Larva;Libraries;Macular degeneration;Malignant Neoplasms;Mammals;Masks;Measurement;Measures;Medical;Methods;Modeling;Molecular;mosaic;Mus;mutant;Mutate;Mutation;Nature;Nerve Degeneration;novel;Organism;Outcome;Pattern;Phenotype;Plasmids;pleiotropism;prevent;Process;Property;Quality of life;Reiterated Genes;Research;Resources;Retinal Diseases;Role;screening;sensor;single cell genomics;single-cell RNA sequencing;Specific qualifier value;Specificity;Split-Pool Ligation Transcriptome sequencing;success;Technology;technology development;Testing;Tissues;tool;transcription factor;Validation;vector;Vertebrates;Vision;Visual;whole genome;Work;Zebrafish

PROJECT_TITLE: Mosaic in Vivo Perturbation (MVP) for systematic assessment of gene function in the eye

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]