NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Infant Mortality;Orphan Drug;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: CHICAGO

ORG_NAME: LURIE CHILDREN'S HOSPITAL OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative Hypoplastic left heart syndrome (HLHS) is one of the most complex forms of congenital heart disease (CHD), with a reported incidence of 0.2 per 1000 live births, or 3% of children born with CHD. Once a universally fatal diagnosis, dramatic improvements in three staged palliative operations now allow the single right ventricle (RV) to functionally support the total circulation. Despite these strides in medical care, the mortality rate of these infants remains as high as 25 to 35% during the first year of life and continues with a high mortality rate for the rest of their life. High mortality may in part be related to RV performance in these challenging infants. The major objective of the proposed study is to assess for the first time in a single blinded randomized control trial (RCT), whether intramyocardial injection of MSCs is beneficial for HLHS patients. The study is randomized so that during the Stage II operation, half the patients will receive MSC treatment and the other half will receive standard of care. The two groups will receive the same care thereafter and CMR will be used to assess RV performance.

PI_NAMEs: BERGER, STUART  (contact);HARE, JOSHUA M;KAUSHAL, SUNJAY

PROGRAM_OFFICER_NAME: BURNS, KRISTIN

PROJECT_TERMS: Address;Allogenic;Anastomosis - action;Arrhythmia;Back;Basic Science;Biological Markers;Cardiac;cardiac magnetic resonance imaging;Cardiac Myocytes;Cardiopulmonary Bypass;Caring;Cell secretion;Child;Childhood;Circulation;Clinical;Clinical Research;clinical research site;Clinical Trials;Complex;Computer Models;congenital heart abnormality;Data;Data Coordinating Center;Death Rate;design;Diagnosis;Down-Regulation;EFRAC;Enrollment;Etiology;exosome;experience;Failure;Family suidae;GDF15 gene;Goals;heart function;Heart Transplantation;Human;Hypertrophy;Hypoplastic Left Heart Syndrome;improved;Incidence;Infant;inhibitor;Injections;Ischemia;Life;Live Birth;MADH2 gene;Magnetic Resonance;Measures;Medical;meetings;member;Mesenchymal Stem Cell Transplantation;Mesenchymal Stem Cells;mortality;Myocardium;novel;novel therapeutic intervention;novel therapeutics;operation;Outcome;Outcome Measure;palliative;Pathway interactions;Patients;Performance;Phase;phase 1 study;phase 3 study;Phase III Clinical Trials;Phosphorylation;Physiological;Plasma;porcine model;Postoperative Period;pre-clinical;preclinical study;pressure;prevent;primary endpoint;primary outcome;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Reporting;Research Design;Resources;Rest;Right Ventricular Dysfunction;Right Ventricular Hypertrophy;right ventricular remodeling;Right ventricular structure;Safety;safety and feasibility;secondary endpoint;secondary outcome;Serious Adverse Event;Serum;Single-Blind Study;standard of care;stem cell biology;stem cell delivery;stem cell exosomes;stem cell therapy;stem cells;Sudden Death;Surgeon;Techniques;Testing;Therapeutic;therapeutic miRNA;Time;transcriptome sequencing;Transforming Growth Factor beta

PROJECT_TITLE: 1/2 Allogeneic Human Mesenchymal Stem Cell (MSC) Injection in Patients with Hypoplastic Left Heart Syndrome: A Phase IIb Clinical Trial

STUDY_SECTION: CLTR

STUDY_SECTION_NAME: Clinical Trials Review Study Section[CLTR(MA)]


ADMINISTERING_IC: HG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_COUNTRY: UNITED STATES

ORG_DEPT: CHEMISTRY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: Project Narrative The proposed research will develop highly sensitive and selective chemical methods to label and sequence 5-hydroxymethylcytosine (5hmC) in DNA at the single-base resolution and single-cell level. New methods that can combine enrichment and base-resolution sequencing of 5-methylcytosine (5mC) in DNA are also proposed. These new methods are expected to enable breakthrough advances in basic biomedical research as well as clinical biomarker studies.

PI_NAMEs: HE, CHUAN  (contact)

PROGRAM_OFFICER_NAME: CHADWICK, LISA

PROJECT_TERMS: Adopted;Antibodies;Azides;base;Base Excision Repairs;Basic Science;Binding;Binding Proteins;Biological Markers;Biomedical Research;Biotin;bisulfite sequencing;Cell Differentiation process;cell free DNA;cell type;Cells;Chemicals;Clinical;clinical application;clinical biomarkers;clinical diagnosis;clinical prognosis;Cytosine;demethylation;Detection;Development;Dioxygen;Dioxygenases;Disease;disease diagnosis;disease prognosis;DNA;DNA analysis;DNA mapping;DNA Methylation;DNA Modification Process;Embryonic Development;Enhancers;Enzymes;Epigenetic Process;epigenome;Family;Gene Expression;gene repression;Genes;Genetic Transcription;genome-wide;Genomic Imprinting;Health;Heterochromatin;High-Throughput Nucleotide Sequencing;Human;human disease;Human Genome;human tissue;Immunoprecipitation;Investigation;Iron;Label;Laboratories;Mammals;Maps;Mediating;member;Methods;Methylation;Modification;Mus;oxidation;Play;Procedures;Process;prognosis biomarker;programs;promoter;Proteins;Recombinants;Regulation;Repetitive Sequence;Research;Resolution;Retrotransposon;Role;Sampling;seal;Sensitivity and Specificity;Site;stoichiometry;success;Technology;Thymine DNA Glycosylase;Tissues;Variant;whole genome;X Inactivation

PROJECT_TITLE: Labeling and sequencing of 5hmC and 5mC in DNA-Renewal

STUDY_SECTION: SBCA

STUDY_SECTION_NAME: Synthetic and Biological Chemistry A Study Section[SBCA]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Prevention;Women's Health Research

ORG_CITY: DAVIS

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PROJECT NARRATIVE Benign breast diseases are common findings on breast biopsy, and certain benign diagnoses are known to be associated with a high risk for development of breast cancer; however, the etiology and risk of cancer associated with other specific benign breast diseases have not been extensively studied or quantified. This study leverages data on over 2.1 million women from 7 diverse Breast Cancer Surveillance Consortium breast imaging registries across the U.S. with up to 25 years of follow-up to identify specific benign breast disease diagnoses and accurately quantify their associations with future breast cancer risk. Our results will provide a better understanding of the relationship between benign breast disease and breast cancer risk among premenopausal and postmenopausal women and by time since diagnosis and may identify subgroups of women most likely to benefit from targeted screening and other prevention efforts.

PI_NAMEs: SATTAYAPIWAT, OLIVIA KAYAN (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: Address;advanced breast cancer;aggressive breast cancer;Architecture;Atypia;Benefits and Risks;Benign;Biometry;Biopsy;Breast;Breast biopsy;Breast Cancer Risk Factor;Breast Cancer Surveillance Consortium;Breast Diseases;breast imaging;breast pathology;cancer diagnosis;cancer epidemiology;cancer risk;Cancerous;career;Categories;Cessation of life;classification trees;clinical practice;Competence;Cox Proportional Hazards Models;Data;Descriptor;Development;Diagnosis;Disease Clusterings;disease diagnosis;disease diagnostic;disorder risk;Duct (organ) structure;Early Diagnosis;Environment;Etiology;Expert Opinion;follow-up;Future;Goals;Harm Reduction;high risk;High Risk Woman;Histologic;Hyperplasia;improved;Incidence;Individual;individualized prevention;Knowledge;Lesion;Lobular;lobular breast carcinoma in situ;Malignant Breast Neoplasm;Mammary Gland Parenchyma;Mammographic screening;Medicine;Menopausal Status;Mentors;Modification;mortality;multidisciplinary;Noninfiltrating Intraductal Carcinoma;Normal Range;Palpable;Pathologic;Pathology;Performance;Postmenopause;Premenopause;Prevention;Prevention strategy;primary outcome;Primary Prevention;Proliferating;Recording of previous events;Registries;Research;Research Personnel;Resources;Risk;Risk Estimate;Risk Factors;risk prediction;risk prediction model;Sample Size;screening;secondary outcome;Secondary Prevention;Subgroup;Technical Expertise;Time;Training;Training and Education;United States;Variant;Woman;women's diagnosis;Women's Group;Work

PROJECT_TITLE: Advancing Evidence of the Associations between specific Benign Breast Diagnoses and Future Breast Cancer Risk

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F18-A(20)L]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Precision Medicine;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative By conventional measures, women with estrogen receptor positive invasive lobular breast cancer (ILC) have poor responses to standard treatment approaches. Given the poor outcomes seen in patients with ILC, there is a great need to improve patient selection for standard chemotherapy and identify novel treatment strategies. In this project, I will develop a new clinical prediction tool to identify chemotherapy responders, and conduct a pilot trial testing a novel agent for estrogen receptor positive tumors.

PI_NAMEs: MUKHTAR, RITA  (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Address;Adjuvant Chemotherapy;Adjuvant Study;Affect;arm;BCL1 Oncogene;Biological Assay;Biological Markers;biomarker development;Breast Cancer Patient;Cancer Burden;cancer clinical trial;career;Cessation of life;Characteristics;chemotherapy;Classification;Clinical;Clinical Investigator;clinical practice;clinical predictors;Clinical Research;Clinical Trials;clinically relevant;cohort;Collaborations;Cytotoxic Chemotherapy;Data;Data Set;design;Detection;Development;Diagnosis;diagnostic strategy;Disease;Disease-Free Survival;Disparate;Drug Combinations;Duct (organ) structure;E-Cadherin;Effectiveness;Endocrine;Estrogen receptor positive;Evaluation;experience;Future;Gene Expression;Gene Expression Profile;Gene Expression Profiling;genetic signature;Goals;Heterogeneity;high risk;Histopathology;hormone receptor-positive;hormone therapy;Image;imaging biomarker;improved;In complete remission;indexing;individual patient;individualized medicine;Indolent;infiltrating duct carcinoma;inhibitor;Institution;Knowledge;Lead;Learning;Lobular;Lobular Carcinoma;Lymph Node Involvement;Machine Learning;Malignant Breast Neoplasm;Malignant Neoplasms;Mammography;Measures;Mentors;Mentorship;Methods;Molecular;Molecular Profiling;Morbidity - disease rate;Neoadjuvant Therapy;novel;oncotype;Operative Surgical Procedures;Outcome;Pathologic;Pathway interactions;Patient Care;patient oriented;Patient Selection;Patients;personalized approach;Pharmacologic Substance;Pilot Projects;pilot trial;Positive Lymph Node;Prediction of Response to Therapy;predictive modeling;predictive tools;programs;prospective;protein expression;Protocols documentation;radiomics;Randomized;randomized trial;Recurrence;Reporting;Research;Residual Cancers;Residual state;responders and non-responders;response;Risk;Running;Safety;side effect;skills;specific biomarkers;standard care;Statistical Methods;targeted agent;targeted treatment;Testing;Therapeutic;Therapy trial;Time;tissue biomarkers;tool;Training;treatment choice;treatment responders;treatment response;treatment strategy;tumor;United States;Woman;women's clinical trial;women's treatment;Work

PROJECT_TITLE: Identifying responders to chemotherapy in invasive lobular carcinoma of the breast: development of a multivariable clinical prediction tool

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Inflammatory Bowel Disease;Nutrition;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: STANFORD

ORG_DEPT: PEDIATRICS

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Ulcerative colitis continues to increase in children and environmental factors such as diet play a vital role in the management of the disease. Sulfites are potentially harmful compounds that must be detoxified in many cells and tissues, but they are also ubiquitous in our diet as preservatives. To inform future practices on the dietary management of pediatric ulcerative colitis, this study proposes innovative scientific approaches to determine whether sulfites interfere with the normal function of the colon function in health and in UC.

PI_NAMEs: OJO, BABAJIDE  (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Adverse effects;Affect;American;Animal Model;Award;Bar Codes;biobank;Biology;Biopsy;career;Cell Differentiation process;Cell Respiration;Cells;Cellular Metabolic Process;Child;Child Nutrition;Childhood;Chromatin;Colitis;Colon;Colonic inflammation;Complex;Consumption;Data;Defect;Developed Countries;Diet;dietary;Dietary Factors;Digestive System Disorders;Disease;Disease Management;disease model;disorder control;Drug Metabolic Detoxication;Environment;Environmental Risk Factor;epigenome;epigenomics;epithelial injury;epithelial repair;epithelial stem cell;Epithelium;Excision;Exposure to;feeding;Food Preservatives;Foundations;Funding;Future;gastrointestinal epithelium;Genes;Goals;gut microbiota;Health;Homeostasis;Human;human tissue;Impairment;in vivo;Incidence;Inflammatory Bowel Diseases;Ingestion;inhibitor;innovation;Intake;intestinal barrier;intestinal epithelium;Intestines;Maintenance;Metabolic;Metabolism;Mitochondria;Mitochondrial DNA;mitochondrial DNA mutation;mitochondrial dysfunction;mitochondrial metabolism;Modeling;molybdenum cofactor;mouse model;Mus;Mutation;Natural regeneration;nutrition;Organoids;Outcome;Pathway interactions;Patients;pediatric patients;Pediatric ulcerative colitis;Phase;Phenotype;Physiological;Play;Predisposition;Prevalence;programs;Publishing;Recovery;regenerative;Research;Research Personnel;response;Role;Safety;Sampling;Science;self-renewal;Shapes;Signal Transduction;single cell ATAC-seq;Site;skills;Source;stem cell differentiation;stem cells;Sulfites;Sulfur;tissue stem cells;Tissues;Training;transcriptomics;Ulcerative Colitis;United States National Institutes of Health;Variant;western diet;Work

PROJECT_TITLE: Dysregulation of Epithelial Metabolism and Regeneration by Sulfite Exposure in Pediatric Ulcerative Colitis

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: DURHAM

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative: I determined how SARS-CoV-2 nucleocapsid (N) protein recognizes viral RNA to undergo condensation in an RNA sequence, RNA structure, and temperature dependent manner. I will uncover new modes of condensation function by identifying how RNA-RNA interactions are modulated by condensation as well as identifying which N role(s) in viral replication require condensation. Lastly, I will design and test novel inhibitors of N condensation including synthetic RNA-binding proteins and small molecules with the goal of eventually developing treatments for SARS-CoV-2.

PI_NAMEs: RODEN, CHRISTINE ANNE (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;Address;betacoronavirus;Biochemical;Biochemistry;Biological Assay;Biological Models;Biological Process;Biology;Biomedical Engineering;biosafety level 3 facility;Cells;Cellular Assay;Cellular biology;Chemicals;Collaborations;Coronavirus;COVID-19 treatment;crosslink;Cytoplasm;design;Development;dimer;Dimerization;Disease;Disease Outbreaks;Double-Stranded RNA;Failure;future outbreak;Generations;genetic manipulation;Genome;Goals;Growth;Health Benefit;inhibitor;Inosine Diphosphate;interest;Lead;Learning;Maps;Membrane;Modeling;Molecular;Molecular Biology;Mutation;novel;novel therapeutics;Nucleocapsid;Nucleocapsid Proteins;Peptides;Phase;Phenotype;Physical condensation;Physiological;Process;Property;protein crosslink;protein phosphatase inhibitor-2;Proteins;Proteome;Public Health;recruit;Research;Research Personnel;RNA;RNA Binding;RNA Probes;RNA Sequences;RNA Viruses;RNA-Binding Proteins;RNA-Protein Interaction;Role;Running;Safety;Sensitivity and Specificity;skills;small molecule;small molecule inhibitor;small molecule libraries;Specific qualifier value;Structural Protein;Structure;symposium;System;Techniques;Temperature;Testing;Time;Training;Translational Regulation;Translations;Universities;Viral;Viral Physiology;viral RNA;virology;Virus;Virus Replication;Work

PROJECT_TITLE: Double-stranded RNA dictates SARS-CoV-2 nucleocapsid condensation temperature

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Clinical Research;Pediatric

ORG_CITY: NEW YORK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: NEW YORK UNIVERSITY

ORG_STATE: NY

PHR: PROJECT NARRATIVE This research tests the role of everyday walking experience in the development of adaptability in infant walking skill. Despite abundant research characterizing improvements in walking skill under uniform conditions (bare feet, flat ground), little research tested infants’ ability to adapt their walking patterns to changing conditions (i.e., changes to the body or environment). The proposed project will characterize experience-related changes in the adaptability of walking in typically developing infants and thus has the potential to inform early interventions to improve locomotor function for children with disabilities.

PI_NAMEs: HOSPODAR, CHRISTINA M (contact)

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TERMS: Address;Affect;Age;Ankle;Back;behavior measurement;Biomechanics;Child;Child Support;Clinical assessments;Collaborations;Computer Vision Systems;coping;density;design;Development;Disabled Children;Early Intervention;Environment;Equilibrium;Euclidean Space;experience;experimental study;falls;foot;Gait;Growth;Hip region structure;improved;Infant;innovation;Intervention;Joints;Knee;Knowledge;Learning;Length;Machine Learning;Measures;mechanical force;Motor;motor behavior;motor control;Motor Skills;Movement;novel;Outcome Measure;Pattern;Recording of previous events;Research;Research Personnel;Role;Shoes;skills;spatiotemporal;Speed;Surface;Techniques;Testing;theories;Time;Toes;walker;Walking;Work

PROJECT_TITLE: Adaptability in infant walking


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Estrogen;Neurosciences;Nutrition;Obesity

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: NUTRITION

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: Project Narrative Our basic research is focused on elucidating the connections and functions of aromatase neurons relevant to energy balance control. In addition to the urgent search for novel controls of body weight with the hope of identifying new anti-obesity treatments, the urgency of the current proposal is increased by the fact that pharmaceuticals inhibiting aromatase production are prescribed to many women yearly. They are capable of crossing the blood brain barrier, and their ability to affect behavior and metabolism via action on brain aromatase is poorly understood.

PI_NAMEs: SKIBICKA, KAROLINA P (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Adult;Affect;Amygdaloid structure;Androgens;Appetite Stimulants;Aromatase;Aromatase Inhibition;Aromatase Inhibitors;Basic Science;Behavior;Behavior Control;Behavioral;blood-brain barrier crossing;Body Temperature;Body Weight;Brain;Brain region;Brown Fat;Cell Nucleus;Cells;Clinic;Data;design;Desire for food;Diet;Disease;Disinhibition;Distal;energy balance;Energy Metabolism;Enzymes;Estradiol;Estrogen Receptors;Estrous Cycle;experimental study;feeding;Feeding behaviors;Female;Food;Functional disorder;Goals;Gonadal Steroid Hormones;Gonadal structure;Health;Homeostasis;Human;Hyperphagia;Hypothalamic structure;hypothalamic-pituitary-thyroid axis;knock-down;Lateral;Ligands;Link;liquid chromatography mass spectrometry;Maintenance;male;Measurement;Measures;Mediator;men;Metabolic;Metabolic Control;Metabolism;Molecular;motivated behavior;neural;neural circuit;Neuroanatomy;neurochemistry;Neurons;novel;Obesity;obesity treatment;obesogenic;overexpression;paraventricular nucleus;Pathway interactions;Pharmacologic Substance;Physiologic Thermoregulation;Physiological;Physiology;Plasma;Population;Production;Rattus;receptor;Research;response;Rodent;Role;Self-control as a personality trait;sex;Site;Source;Steroids;System;Testing;Testosterone;Thermogenesis;translational potential;Viral Vector;Weight Gain;Weight maintenance regimen;Woman;Work

PROJECT_TITLE: Neuroanatomical substrates underpinning brain aromatase control of feeding behavior and metabolic homeostasis

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging

ORG_CITY: CHARLOTTE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF NORTH CAROLINA CHARLOTTE

PHR: Public Health Relevance Statement PROJECT NARRATIVE The importance of this project for human health is to reveal fundamental new insights into the molecular mech- anism by which the gut communicates with the muscle to promote tissue-health, stress resilience and lifespan extension. This knowledge will be crucial if we are to design effective small molecules aimed at activating key intercellular signaling components to combat age-associated degenerative diseases and prolong healthy tissue function throughout life.

PI_NAMEs: VAN OOSTEN-HAWLE, PATRICIJA  (contact)

PROGRAM_OFFICER_NAME: OROSZ, ANDRAS

PROJECT_TERMS: age related;age related neurodegeneration;age-related disease;Aging;Alzheimer's Disease;Animals;Auxins;Binding;Binding Sites;Biological Models;Caenorhabditis elegans;Cell membrane;Cell Nucleus;Cells;Chromatin;Clinical;combat;Communication;Data;Degenerative Disorder;Dementia;design;Development;Disease;Distal;Endocrine;Enteroendocrine Cell;extend lifespan;extracellular;Genes;genetic approach;Genetic Transcription;Genome;Genomics;Goals;Guanylate Cyclase;Health;healthspan;healthy aging;Heat Stress;Heat-Shock Proteins 70;Heat-Shock Proteins 90;homeodomain;Hormones;Human;Impaired health;improved;insight;Intervention;Intestines;knock-down;Knowledge;Life;life span;Longevity;Mediating;Mediator;Membrane;Metabolic Diseases;Methodology;Molecular;Molecular Chaperones;Muscle;Muscle Cells;muscle degeneration;Myopathy;Names;Nervous System;Neurons;Neuropeptides;new therapeutic target;Organ;Organism;Outcome;paracrine;pathogen;Pathway interactions;Patients;Peptides;pharmacologic;preservation;Process;programs;protein misfolding;Proteins;Proteomics;proteostasis;public health relevance;Publications;Quality Control;Regulation;Reporting;response;Risk;Role;sarcopenia;Set protein;Signal Induction;Signal Pathway;Signal Transduction;small molecule;Stress;stress resilience;Stress Response Signaling;System;Testing;Therapeutic;therapeutic target;Time;Tissues;transcription factor;transcriptome;transmission process;Up-Regulation;Visualization;Work

PROJECT_TITLE: Gut stress-induced intercellular signaling networks promoting longevity and proteostasis

STUDY_SECTION: CMAD

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Genetics;Hematology;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE Acute myeloid leukemia is one of the deadliest blood cancers, yet decades-old chemotherapies remain the standard of care for treatment due to its molecularly heterogeneous pathobiology. The epigenetic repression of LINE1 retrotransposons (“jumping genes”) is a newly recognized feature of AML-initiating cells to maintain malignant self-renewal, differentiation blockade, and genomic stability, whereas aberrant LINE1 reactivation impairs AML development. This project aims to elucidate the functional and mechanistic role of retrotransposon- mediated interferon signaling in AML pathogenesis, knowledge of which can inform whether and how the retrotransposon-innate immune crosstalk may be leveraged to selectively eradicate AML-initiating cells.

PI_NAMEs: LEE, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Ablation;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Adult;Affect;Apoptosis;Biology;cancer type;Cell Aging;Cell Cycle Arrest;Cell Proliferation;chemotherapy;clinical heterogeneity;Clustered Regularly Interspaced Short Palindromic Repeats;Complementary DNA;CRISPR-mediated transcriptional activation;cross immunity;Dependence;Development;DNA;Double-Stranded RNA;Elements;Epigenetic Process;epigenetic silencing;feature detection;Gene Expression Regulation;gene product;Genetic;Genetic study;Genetic Transcription;Genome Stability;Genomic DNA;Hematologic Neoplasms;Hematopoiesis;Hematopoietic;Hematopoietic Neoplasms;Human;Immune;Impairment;In Vitro;in vivo;Individual;Inflammation;inhibitor;Innate Immune Response;Interferon Activation;Interferon Type I;Interferons;Jumping Genes;knock-down;Knockout Mice;Knowledge;leukemia;leukemia initiating cell;leukemogenesis;Link;Long Interspersed Elements;Maintenance;Malignant - descriptor;Malignant Neoplasms;Mediating;mimicry;MLL-AF9;Modeling;Molecular;mouse model;Mus;mutant;Myelogenous;Myeloid Leukemia;Natural Immunity;Nature;novel therapeutics;Nucleic Acids;overexpression;Pathogenesis;Pathway interactions;Patients;receptor;Reporting;Repression;response;Retrotransposition;Retrotransposon;Reverse Transcription;RNA;Role;self-renewal;sensor;Signal Pathway;Signal Transduction;small hairpin RNA;standard of care;Survival Rate;targeted treatment;Therapeutic;Transcript;Transgenic Mice;tumor;tumorigenesis;Viral;Work;Xenograft procedure

PROJECT_TITLE: Dissecting the functional role of LINE1 retrotransposon-mediated interferon signaling in myeloid leukemia


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Injury;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Mental Health;Pediatric;Physical Injury - Accidents and Adverse Effects;Prevention;Telehealth;Violence Research;Youth Violence

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE This project aims to develop and evaluate a digital mental health intervention (DMHI) for adolescents who engage in nonsuicidal self-injury (NSSI) and who are not currently engaged in treatment. I will employ user- centered design methodologies to understand adolescents' specific needs and preferences, which will guide the development of a scalable, low-intensity DMHI designed to be implemented within the digital offerings of a large mental health advocacy website. The DMHI will support the acquisition and practice of skills to reduce NSSI frequency, and encourage use of external supports to increase further help-seeking among high-risk adolescents who are currently unable or uninterested in accessing traditional psychological treatments.

PI_NAMEs: KRUZAN, KAYLEE PAYNE (contact)

PROGRAM_OFFICER_NAME: SIMS, BELINDA ENITA

PROJECT_TERMS: 14 year old;17 year old;Address;Adolescence;Adolescent;adolescent health;Advocacy;advocacy organizations;Affect;Anxiety;Assessment tool;Attenuated;Attitude;Award;barrier to care;Behavior;behavior change;Behavioral;career;chatbot;Cognitive;Collaborations;Conduct Clinical Trials;cost;Data;demographics;design;Development;digital;digital delivery;digital intervention;digital mental health;Disclosure;Dissemination and Implementation;Distress;Early Intervention;early onset;effectiveness-implementation RCT;effectiveness/implementation hybrid;effectiveness/implementation trial;efficacy testing;Emotional;Ensure;Ethnic Origin;evidence base;Evidence based practice;follow-up;Frequencies;Future;Gender;Goals;health literacy;help-seeking behavior;high risk;high-risk adolescents;Hospitalization;implementation design;implementation evaluation;improved;Informal Social Control;Intervention;Interview;iterative design;Leadership;Link;literacy;Lived experience;meetings;Mental Depression;Mental Health;Methodology;Methods;Modeling;Motivation;non-suicidal self injury;Participant;Pathway interactions;Persons;pilot trial;Population;Positioning Attribute;preference;Prevalence;prevent;primary outcome;Process;programs;psychiatric comorbidity;psychoeducation;psychologic;Quality of life;Race;Randomized;Randomized, Controlled Trials;recruit;Reporting;Research;Research Activity;Research Personnel;Research Project Grants;Resources;Risk;secondary outcome;Self Assessment;Severities;skills;skills training;social stigma;Stigmatization;suicidal;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Testing;therapy design;Time;Tissues;Training;treatment effect;usability;user centered design;web site

PROJECT_TITLE: Developing a Digital Intervention for Adolescent Nonsuicidal Self-injury

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BOSTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PHR: Narrative Microglia, the resident immune cells of the brain, are one of the causal cell types of neurodegenerative disease, especially in Alzheimer’s disease (AD). While neuronal dysfunctions prior to cognitive impairment detected in AD patients, it is unclear how microglia affect neuronal function especially selectively vulnerable brain regions of prodromal AD stage. The goal of this project is to understand the mechanisms of AD microglia effect in brain network and determine the efficacy of microglia-targeted pharmacological and cell therapeutic interventions.

PI_NAMEs: TCW, JULIA  (contact)

PROGRAM_OFFICER_NAME: THOMAS, CIBU PAUL

PROJECT_TERMS: Acceleration;Acute;Adult;Affect;Aging;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer's disease therapeutic;Amyloid;Amyloidosis;antagonist;Apolipoprotein E;apolipoprotein E-3;Astrocytes;Binding;Brain;brain cell;Brain region;brain repair;Cell Physiology;cell type;Cells;Cognitive deficits;Development;Disease;Disease Progression;efficacy evaluation;Electronics;Electrophysiology (science);entorhinal cortex;Environment;Excision;Exhibits;Functional disorder;Genes;Genetic;genome wide association study;Genotype;Gliosis;Goals;Hippocampus;Human;human induced pluripotent stem cells;Immune;immune activation;Immunoassay;Impaired cognition;Impairment;in vivo;Infiltration;Inflammation;Inflammatory;interdisciplinary approach;Intervention;Intravenous;Late Onset Alzheimer Disease;Lead;Macrophage Colony-Stimulating Factor Receptor;Memory;Microglia;Modeling;Molecular;mouse model;Mus;Neonatal;Nerve Degeneration;Neurodegenerative Disorders;Neuronal Dysfunction;Neurons;neurotoxicity;Newborn Infant;novel therapeutics;Pathogenesis;Pharmaceutical Preparations;pharmacologic;preclinical development;prodromal Alzheimer's disease;progenitor;protective effect;Protein Isoforms;Proteins;Recovery;Research;risk variant;Role;self-renewal;Senile Plaques;single-cell RNA sequencing;Synapses;Therapeutic;Therapeutic Intervention;transcriptomics;Traumatic Brain Injury;virtual reality;way finding;Xenograft procedure

PROJECT_TITLE: Microglia targeted interventions in prodromal Alzheimer's disease stage

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Urologic Diseases;Vaccine Related

ORG_CITY: SEATTLE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: NARRATIVE The primary goal of this proposal is to understand how the ability of most common Escherichia coli adhesin, FimH, to dynamically change its structure is affecting the type of antibodies that are produced against it. We intend to perform a comprehensive analysis of the molecular and protective properties of the antibodies in context of the their specificity and inhibition of the bacterial cell adhesion and ability to cause UTI.

PI_NAMEs: CARTWRIGHT, MARK ;SOKURENKO, EVGENI VENIAMINOVIC (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Adhesives;Affect;Affinity;antibiotic resistant infections;Antibodies;Antibody Repertoire;Antibody Response;Antimicrobial Resistance;Attention;Bacteria;Bacterial Adhesins;Bacterial Adhesion;Bacterial Infections;Binding;Biocompatible Materials;Black race;Cell Adhesion;Cell-Matrix Junction;Cells;Code;Color;Communities;conformer;Cystitis;Effectiveness;Elderly;Engineering;Epitopes;Escherichia coli;Escherichia coli Adhesins;fimbria;Fimbriae Proteins;Fimbrial Adhesins;Goals;Human;Immune response;Immunity;Immunoglobulin G;in vivo;Infant;Infection;Invaded;Journals;kidney infection;Lectin;Ligands;Mannose;Mannose Binding Lectin;mannose receptor;Maps;Mediating;Medicine;Microbial Biofilms;Microbiology;Molecular;Molecular Analysis;Molecular Biology;Molecular Conformation;Monoclonal Antibodies;Morbidity - disease rate;mortality;mouse model;Multi-Drug Resistance;Nature;neutralizing antibody;nosocomial UTI;novel strategies;Passive Immunization;Pathogenesis;pathogenic bacteria;pathogenic microbe;Pilum;polyclonal antibody;Population;Property;Proteins;Public Health;Receptor Cell;response;Specificity;Structure;Testing;type 1 fimbriae;Universities;Urinary tract infection;Uropathogenic E. coli;Urothelium;urovirulent isolates;Vaccinated;Vaccination;vaccine candidate;Vaccine Design;vaccine development;Vaccines;Virus Diseases;Washington;young woman

PROJECT_TITLE: Optimization of protective antibodies response against bacterial adhesins

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


NIH_SPENDING_CATS: Diabetes;Nutrition;Obesity

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative The studies in this grant proposal address the molecular mechanisms of mitochondrial cristae biogenesis and respiratory/thermogenic function in specialized brown and beige adipocytes. These mechanisms are central to our understanding of energy balance linked to obesity and type 2 diabetes.

PI_NAMEs: PUIGSERVER, PERE  (contact)

PROGRAM_OFFICER_NAME: LYNCH, CHRISTOPHER

PROJECT_TERMS: Address;Adipocytes;Adipose tissue;Adrenergic Agents;Adult;Agonist;Applications Grants;bariatric surgery;Biogenesis;Body Temperature;Body Weight;Calories;Clinical;cold stress;cold temperature;combat;Complex;cost;cost effective treatment;Coupled;Crista ampullaris;Devices;diabetic;Diet;dietary;dietary control;Electron Transport;energy balance;Energy Metabolism;Exercise;Exhibits;expectation;Fatty acid glycerol esters;feeding;gain of function;Genetic;glycosylation;Goals;Health;Heart;High Fat Diet;Human;Impairment;In Vitro;in vivo;Inner mitochondrial membrane;Intake;Knockout Mice;Life;Link;loss of function;Malignant Neoplasms;Metabolic;Metabolic Diseases;Mitochondria;mitochondrial fitness;Mitochondrial Proteins;Molecular;Molecular Chaperones;Molecular Profiling;mouse model;Mus;non-compliance;Non-Insulin-Dependent Diabetes Mellitus;Obesity;OPA1 gene;Organelles;organizational structure;Outcome;Outcome Study;Outer Mitochondrial Membrane;Oxygen Consumption;PERK kinase;Phenotype;protein complex;Protein Import;Proteins;Protons;Reaction;Regimen;Regulation;Respiration;respiratory;Respiratory physiology;respiratory protein;response;Risk;Signal Transduction;Signaling Protein;Stimulus;Structure;Thermogenesis;Tubular formation;UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase;Virus Diseases;Weight Gain

PROJECT_TITLE: Regulatory mechanisms of mitochondrial cristae biogenesis and thermogenic function

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breast Cancer;Cancer;Gene Therapy;Genetics;Immunotherapy;Women's Health Research

ORG_CITY: HOUSTON

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE Chimeric antigen receptor macrophage (ChARM) therapy offers great promises against solid tumors, but their ex vivo production is complex and technically challenging. The proposed research aims to investigate an innovative strategy of producing ChARMs in vivo using macrophage-targeting exosomes loaded with CAR- encoding mRNA. If successful, the results generated from the proposal will pave the way for a new strategy to produce CAR cells in vivo and greatly expand the utility of cell therapy against solid tumors.

PI_NAMEs: JIANG, WEN  (contact);KIM, BETTY

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Animals;Antibodies;Antigen Presentation;antigen-specific T cells;antitumor effect;Antitumor Response;Autologous;Breast;Breast Cancer Cell;Breast Cancer Model;cancer immunotherapy;CAR T cell therapy;CD8B1 gene;Cell Therapy;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;Complex;Consumption;cytokine;design;Dose;draining lymph node;engineered exosomes;Engineering;Epidermal Growth Factor Receptor;Exhibits;exosome;experimental study;extracellular;Face;Flow Cytometry;Gene Expression;Generations;Genes;Hematologic Neoplasms;Human;Immune;immune activation;Immunocompetent;Immunofluorescence Immunologic;Immunologic Stimulation;In Vitro;in vivo;Infusion procedures;innovation;insight;interest;ITGAM gene;lymph nodes;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Maps;Mediating;Membrane;Messenger RNA;Metastatic breast cancer;mRNA delivery;multiphoton microscopy;Mus;Myeloid-derived suppressor cells;Nature;novel strategies;Pathway interactions;patient derived xenograft model;Phagocytes;Phagocytosis;Phenotype;Population;Pre-Clinical Model;Preparation;Production;programs;protein expression;receptor;Receptor Cell;reconstitution;Regimen;Research;Solid;Solid Neoplasm;Spatial Distribution;Specificity;T cell infiltration;T-Lymphocyte;Testing;Therapeutic;Time;Toxic effect;transcriptome sequencing;transcriptomics;tumor;tumor growth;tumor heterogeneity;tumor microenvironment;Viral Vector

PROJECT_TITLE: Engineering In Vivo Chimeric Antigen Receptor Macrophages (CARMs) using mRNA-exosomes for Cancer Immunotherapy


NIH_SPENDING_CATS: Clinical Research;Genetics;HIV/AIDS;Infectious Diseases;Mental Health;Neurosciences

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Some people living with HIV on effective antiretroviral therapy show signs of inflammation in their brain and continue to experience cognitive impairment. This study will examine whether HIV leaves molecular “scars” changing gene activity in specific types of immune cells that produce inflammation in people’s brains.

PI_NAMEs: CORLEY, MICHAEL JAY (contact);FARHADIAN, SHELLI

PROGRAM_OFFICER_NAME: RAO, VASUDEV RAMACHANDRA

PROJECT_TERMS: 3-Dimensional;Abnormal Myeloid Cell;Acute;antiretroviral therapy;Automobile Driving;Autopsy;Biological;Biological Assay;Biological Markers;biotypes;Blood;Brain;Brain region;brain tissue;CD8B1 gene;Cell Nucleus;Cell Physiology;cell type;Cells;Cellular Assay;Central Nervous System;Cerebrospinal Fluid;Chromatin;Cicatrix;Clinical;Cognition;Cognitive;cognitive control;cognitive function;cognitive testing;Cohort Studies;comorbidity;Congenital neurologic anomalies;Disease;DNA;DNA Methylation;DNA Modification Process;epigenetic marker;Epigenetic Process;epigenome;experience;Gene Expression;gene network;Genes;Genetic Transcription;glial activation;Goals;Health;histone modification;HIV;HIV Infections;HIV-1;HIV-associated cognitive impairment;IL6 gene;Immune;immune activation;Immune system;Impaired cognition;in vivo;Individual;Inflammation;Inflammatory;inflammatory marker;innovation;Interleukin-1 beta;Intervention;lens;life span;Link;Machine Learning;Mediating;Mediator;Memory;Microglia;Molecular;multimodality;multiple omics;Myelogenous;Myeloid Cell Activation;Myeloid Cells;National NeuroAids Tissue Consortium;Nervous System Trauma;Neuroglia;Neuroimmune;neuroinflammation;Neurologic;Neuronal Injury;novel;novel therapeutics;NR4A2 gene;Nucleic Acid Regulatory Sequences;Outcome;Participant;Pathway interactions;Performance;Persons;Population;prevent;programs;protein expression;Proteins;Protocols documentation;Publishing;Research;Resolution;RNA;Role;Sensorimotor functions;Short-Term Memory;single cell analysis;single cell genomics;Specimen;Spinal Puncture;Structure of choroid plexus;success;Syndrome;T memory cell;T-Lymphocyte;Technology;Testing;Therapeutically Targetable;Time;Tissues;TNF gene;transcriptomics;Ventricular;Viral;Viral Pathogenesis;Virus Replication;Work

PROJECT_TITLE: Decoding epigenetic scars of smoldering neuroinflammation and CNS complications in people with HIV


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Machine Learning and Artificial Intelligence;Neurosciences;Rehabilitation

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative Loss of communication is one of the most disabling and distressing symptoms of neurologic disease and injury and is often cited as a primary factor in the decision to withdraw life-sustaining treatments. For the hundreds of thousands of people worldwide living with ALS, muscular dystrophy, brainstem stroke, and other paralyzing conditions, the existing augmentative and assistive devices that attempt to restore communication by adapting residual volitional motor control (e.g., eye gaze) are often slow, error-prone, and difficult to use, leading to high rates of abandonment. Dr. Rubin’s proposed career development and research plan has the potential to greatly improve the lives of this large patient population by studying the neural basis of speech motor control for the purpose of enabling an intracortical brain computer interface able to restore near-fluent rates of communication by decoding intended speech directly from the associated motor cortical neural activity.

PI_NAMEs: RUBIN, DANIEL B (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Algorithms;Amyotrophic Lateral Sclerosis;association cortex;Behavior;behavior influence;brain computer interface;Brain region;Brain Stem Infarctions;Broca's area;career;career development;Caring;Characteristics;Chronic;Climacteric;Clinical Trials;Code;cognitive process;Communication;Communication impairment;Complex;computational neuroscience;computerized tools;Data;Development;Development Plans;didactic education;Dimensions;Disabling;disabling symptom;Distress;Electrophysiology (science);Elements;Endowment;Engineering;Environment;Epilepsy;Evaluation;experience;Eye;flexibility;frontal lobe;functional restoration;Gait;gaze;General Hospitals;Generations;Goals;grasp;Human;improved;Individual;Inferior frontal gyrus;insight;Intervention;Knowledge;Language;Life;Machine Learning;Massachusetts;Mentors;Mentorship;Microelectrodes;Motor;motor control;Motor Cortex;Movement;Muscular Dystrophies;Natural Language Processing;Nervous System Disorder;Nervous System Trauma;neural;neural patterning;Neurologic;Neurologic Symptoms;neurological recovery;neuromechanism;neurophysiology;neuroregulation;Neurosciences;neurotechnology;neurotransmission;next generation;novel;operation;Operative Surgical Procedures;Output;Paralysed;Participant;participant enrollment;patient oriented research;patient population;Patients;Pattern;Performance;Persons;Physicians;Population Dynamics;Principal Component Analysis;Production;prospective;Quality of life;reduce symptoms;Research;research and development;Research Personnel;Research Project Grants;Residual state;Resources;restoration;Self-Help Devices;Semantics;Signal Transduction;skills;Speech;Stream;Stroke;Structure;System;Technology;Temporal Lobe;Time;tool;Training;Translating;Work

PROJECT_TITLE: Neural control of speech generation in human motor cortex

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Estrogen;Genetics;Human Genome;Infertility;Women's Health Research

ORG_CITY: ITHACA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CORNELL UNIVERSITY

PHR: Project Narrative Inappropriate chromosome segregation during meiosis is common in humans and represents the leading cause of miscarriage, birth defects, and infertility. The rate of chromosome segregation errors is strikingly higher in females by comparison to males. This study will use mice from diverse genetic backgrounds to investigate the molecular and genetic factors underlying sex differences that contribute to making female meiosis more error-prone.

PI_NAMEs: HORAN, TEGAN SONIA-ADELINE (contact)

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: Address;Affect;age related;Aneuploidy;Automobile Driving;Candidate Disease Gene;career development;Chromatin;Chromosome Mapping;Chromosome Pairing;Chromosome Segregation;Chromosomes;cohesin;cohesion;Complex Genetic Trait;Computer Analysis;Congenital Abnormality;Data;Development;Development Plans;DNA;DNA Double Strand Break;dosage;Double Strand Break Repair;egg;Ensure;Event;Exhibits;Female;Frequencies;Future;Genes;Genetic;genetic association;Genetic Crossing Over;Genetic Recombination;Genetic Variation;Genome;genomic data;genomic locus;Goals;Heritability;Heterozygote;high resolution imaging;Homeostasis;Homologous Gene;Human;imaging modality;Inbred Strains Mice;Incidence;Infertility;insight;Laboratory mice;Learning;Length;Link;male;Male Sterility;Maps;Mediating;Meiosis;Meiotic Prophase I;Meiotic Recombination;Mentors;MLH1 gene;Molecular;mouse genetics;mouse model;Mouse Strains;MSH4 gene;Mus;mutant;Mutation;nuclease;Oocytes;Organism;Pathway interactions;Pattern;Phase;Phenotype;programs;Proteins;Quantitative Genetics;Quantitative Trait Loci;Recombinants;Regulation;repaired;Reporting;Research;Resolution;Role;Screening Result;segregation;Severities;sex;Sex Differences;sexual dimorphism;Site;skills;sperm cell;Spermatocytes;SPO11 gene;Spontaneous abortion;Stains;Sterility;Structure;superresolution microscopy;Synaptonemal Complex;Techniques;Training;Variant;Work

PROJECT_TITLE: Uncovering molecular factors driving sexual dimorphism in crossing over in diverse mouse genetic backgrounds

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Reproduction, Andrology, and Gynecology Study Section[CHHD-R]


ED_INST_TYPE: SCHOOLS OF EDUCATION

NIH_SPENDING_CATS: Aging;Neurosciences;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Rehabilitation

ORG_CITY: MINNEAPOLIS

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Public Health Narrative The neuromuscular junction (or NMJ) is the point of contact between a motor neuron and skeletal muscle fiber, it initiates muscle contraction and allows physical movement across the lifespan. Without innervation (due to a loss of this connection), muscle fibers cannot contract, significantly reducing function. My work seeks to understand the similarities that occur at the neuromuscular junction with aging and injury to identify treatment targets to improve function and physical movement.

PI_NAMEs: GREISING, SARAH M (contact)

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: Activities of Daily Living;Address;Affect;Age;age related;age related changes;aged;Aging;aging population;Applications Grants;Area;Biogenesis;Biology of Aging;Breathing;career;Cells;Chronic;Clinical;Codependence;Collaborations;comorbidity;Contracts;Data;Denervation;design;Development;disability;Doctor of Philosophy;Education;Effectiveness of Interventions;Elderly;Environment;Evaluation;exercise training;Failure;Fiber;Fostering;Foundations;frailty;functional decline;Functional disorder;Functional impairment;functional improvement;functional restoration;Genomics;Goals;Health;healthspan;human old age (65+);Impairment;improved;Independent Scientist Award;Injury;International;Intervention;K-Series Research Career Programs;Kinesiology;Knowledge;life span;Link;Metabolic;Metabolic dysfunction;mid-career faculty;Minnesota;Mitochondria;mitochondrial dysfunction;Modality;mortality;Motor;Motor Neurons;Movement;Muscle;Muscle Contraction;Muscle Fibers;nerve supply;neuromuscular;neuromuscular function;Neuromuscular Junction;neuromuscular system;neuromuscular transmission;novel;Operative Surgical Procedures;Outcome;overexpression;Pathologic;Pathology;Pathway interactions;Physiology;Population;Public Health;Publishing;Recovery;recruit;regeneration function;regeneration potential;Regenerative capacity;Rehabilitation therapy;repaired;Research;response;sarcopenia;Schools;Scientist;Signal Transduction;Site;Skeletal Muscle;Skeletal muscle injury;skeletal muscle wasting;Synapses;Techniques;Time;tool;Traumatic injury;United States;Universities;volumetric muscle loss;Work

PROJECT_TITLE: Age, Injury, and the Neuromuscular Junction

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Established Investigators and Conference Grants Study Section[AGCD-4]


NIH_SPENDING_CATS: Aging;Lung;Neurosciences;Sarcopenia

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

PHR: PROJECT NARRATIVE By 2030, ~70 million people in the USA will be >65 years of age and ~10 million will be >85 years old, and with aging of our population, the incidence of sarcopenia (age-related muscle wasting and weakness) will increase, which is a significant predictor of chronic disease and mortality in the elderly. The diaphragm muscle is the most important inspiratory muscle, and it is also susceptible to sarcopenia, which may limit higher force expulsive airway clearance behaviors such as coughing and sneezing and thereby increase the risk for airway infections in the elderly. The proposed studies will examine the mechanisms underlying age-related loss of phrenic motor neurons and diaphragm muscle sarcopenia and explore the development of novel therapies to mitigate sarcopenia.

PI_NAMEs: MANTILLA, CARLOS B;SIECK, GARY C. (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Affect;age related;Age Years;age-related muscle loss;Aging;aging related;Amyotrophic Lateral Sclerosis;Atrophic;Behavior;Biogenesis;Brain-Derived Neurotrophic Factor;Breathing;CDC2 gene;cell type;Chronic Disease;Coughing;CREB1 gene;cytokine;Denervation;density;Development;Elderly;endoplasmic reticulum stress;Equilibrium;Experimental Designs;Fiber;Gene Expression;Gene Targeting;human old age (65+);human very old age (85+);Impairment;Incidence;infliximab;injured airway;Intervention;Link;Mediating;Mitochondria;mitochondrial dysfunction;Modeling;mortality;motor neuron degeneration;Motor Neurons;Muscle;Muscle Fibers;Muscle Weakness;Muscular Atrophy;neuron loss;neuronal survival;novel;novel therapeutic intervention;novel therapeutics;older adult;Parkin;Pathway interactions;Performance;Persons;Phosphorylation;PINK1 gene;Population;Predisposition;protective behavior;protein expression;Quercetin;Rattus;Research;respiratory;Respiratory Diaphragm;Respiratory Tract Infections;Risk;Role;sarcopenia;Serine;Serum;Signal Transduction;Sneezing;Techniques;Work

PROJECT_TITLE: Respiratory Control in Old Age

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Clinical Research;Genetics;Lung;Prevention;Tobacco;Tobacco Smoke and Health

PHR: PROJECT NARRATIVE Although cigarette smoke exposure is the leading risk factor for the development of chronic obstructive pulmo- nary disease (COPD), how smoke causes progressive lung damage in COPD is poorly understood. Our prelim- inary data suggest that the abnormal accumulation of iron in alveolar macrophages, sentinel immune cells in the lung, may be a critical link between smoke and its downstream detrimental effects. In this proposal, we will develop and confirm this biological connection between iron, alveolar macrophages, and COPD development using a mouse smoke-exposure model and an extensively characterized multicenter COPD cohort, with the goal of building evidence to eventually develop therapy targeting iron in COPD.

PI_NAMEs: ZHANG, WILLIAM ZHENGYANG (contact)

PROGRAM_OFFICER_NAME: REYES, MADELYN

PROJECT_TERMS: Acceleration;Address;Advisory Committees;Alveolar;alveolar epithelium;Alveolar Macrophages;Alveolus;Area;Award;Biological;Biological Markers;Biology;Bronchoalveolar Lavage Fluid;career development;Cause of Death;Cell Death;Cells;Chronic Obstructive Pulmonary Disease;cigarette smoke;cigarette smoke-induced;cigarette smoke-induced lung injury;Clinical;Clinical Data;clinically relevant;cohort;cytokine;Data;Data Set;Defect;Development;Development Plans;Disease;Disease Marker;disease model;Disease Outcome;Environment;Epithelial Cells;Exhibits;experience;experimental study;exposure to cigarette smoke;extracellular;Ferritin;Functional disorder;Gene Expression;Gene Expression Profile;Genes;Genetic;Genetic Markers;genetic signature;Goals;Histologic;Homeostasis;Human;Immune;immune activation;Immune response;Immunology;improved;Infection;Inflammation;Inflammatory;Inflammatory Response;Injury;innovation;Institution;Iron;iron metabolism;Iron Overload;Knowledge;Link;Lipid Peroxidation;Lung;Lung Diseases;lung injury;Macrophage;Measures;Medicine;Mentorship;Modeling;mouse model;Mus;National Heart, Lung, and Blood Institute;novel;Nuclear Receptor Coactivator 4;pathogen;Pathogenesis;Pathway interactions;Patients;Phagocytes;Phagocytosis;Phenotype;Physicians;Physiological;Pneumococcal Infections;Positioning Attribute;Production;prospective;Proteins;Pulmonary Emphysema;pulmonary function;radiological imaging;Recombinants;Research;Research Personnel;Resources;Respiratory Disease;response;Risk Factors;Role;Scientist;Sentinel;Severity of illness;single-cell RNA sequencing;skills;small airways disease;Smoke;Smoker;Smoking;Source;Streptococcus pneumoniae;Structure of parenchyma of lung;Surrogate Markers;targeted treatment;Techniques;Testing;Therapeutic;therapeutic target;therapy development;Time;tissue injury;Training;transcriptome sequencing;Translational Research;uptake

PROJECT_TITLE: Alveolar Macrophage Iron Overload in COPD Pathogenesis

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(MA)]


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Cancer;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Prevention;Rural Health;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE The COVID-19 pandemic has created unprecedented disruptions in cancer care, and patients with cancer who have slipped through the system unidentified will present with late-stage disease that is too advanced for curative treatments. While studies have demonstrated deficits in new cancer diagnoses, healthcare leaders and policymakers have no data on the impact of these deficits on cancer outcomes or outcome disparities exacerbated in already vulnerable populations. We propose a comprehensive evaluation of this evolving crisis and a framework for systematic surveillance of changing cancer outcomes and disparities.

PI_NAMEs: ENGLUM, BRIAN ROBERT (contact)

PROGRAM_OFFICER_NAME: STINSON, NATHANIEL

PROJECT_TERMS: access disparities;Address;Affect;Age;Black race;Businesses;cancer care;cancer diagnosis;cancer health disparity;Cancer Patient;cancer recurrence;cancer type;Caring;Cessation of life;Characteristics;China;Clinical Services;Colonoscopy;Computerized Medical Record;Country;COVID-19;COVID-19 disparity;COVID-19 pandemic;COVID-19 pandemic effects;Cox Proportional Hazards Models;curative treatments;Data;data infrastructure;Data Set;Databases;design;Detection;Diagnosis;Diagnostic;Diagnostic Procedure;Disease;Disparate;Disparity;Disparity population;Drops;Early Diagnosis;Early identification;Education;Ethnic Origin;Evaluation;experience;Female;Fright;Future;future outbreak;Geographic Locations;Geography;health care availability;Health system;Healthcare;Healthcare Activity;Healthcare Systems;Hospitals;Individual;Informatics;Infrastructure;Inpatients;Intervention;Intervention Studies;Italy;Latino;Location;low socioeconomic status;Malignant Neoplasms;Medical;Methodology;Modeling;mortality;Newly Diagnosed;news;operation;Outcome;outcome disparities;Outpatients;pandemic disease;pandemic disruption;pandemic impact;Patient risk;patient subsets;Patients;Policy Maker;Population;Populations at Risk;preservation;Procedures;programs;Race;repository;Research;Resources;Risk Factors;routine screening;Rural;rural area;SARS-CoV-2 B.1.1.529;SARS-CoV-2 B.1.617.2;SARS-CoV-2 transmission;screening;Screening for cancer;Screening procedure;sex;simulation;Subgroup;System;Testing;Time;transmission process;United States;United States Department of Veterans Affairs;Vaccination;Veterans;Vulnerable Populations

PROJECT_TITLE: Disparities in Cancer Outcomes from the COVID-19 Pandemic

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HSS-B(90)S]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Dental, Oral, and Craniofacial Disease

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Tooth enamel is the most highly mineralized tissue in the human body, formed by the ameloblasts to create a structure consisting of long, thin and intricately interwoven crystals. We will investigate how pH cycling in the enamel matrix directs matrix mineralization and ameloblast function. By understanding these processes, we can, develop strategies to improve resistance to dental caries and enamel fracture, and to synthesize biomaterials with enamel-like structures.

PI_NAMEs: DEN BESTEN, PAMELA K (contact)

PROGRAM_OFFICER_NAME: WAN, JASON

PROJECT_TERMS: Actins;Adhesions;Affect;AKT Signaling Pathway;Ameloblasts;Amelogenesis Imperfecta;amelogenin;Apical;Biocompatible Materials;biomineralization;Calcium;Cell Adhesion;Cell membrane;Cell Physiology;Cells;Cellular Morphology;Code;conditional knockout;crosslink;Cytoskeleton;deamidation;Defect;Dental caries;Dental Enamel;Developmental Process;Enamel Formation;enamel matrix proteins;Enamel Organ;Endocytosis;Environmental Risk Factor;Enzymes;Epigenetic Process;Epithelium;Esthetics;Etiology;extracellular;Extracellular Matrix;Fluorides;fluorosis;Focal Adhesions;Fracture;FRAP1 gene;Gene Expression;Genes;Genetic;Goals;Human body;Hydrolysis;Hydroxyapatites;improved;In Vitro;in vivo Model;Integrins;Knowledge;Maintenance;Maturation-Stage Ameloblast;Mediating;mineralization;Morphogenesis;mouse model;mTOR Signaling Pathway;mutant;novel;Pathway Analysis;PIK3CG gene;polymerization;Polymers;Predisposition;Process;Protein Secretion;protein structure;Proteins;Proto-Oncogene Proteins c-akt;Recombinants;Regulation;repaired;Resistance;Risk Reduction;Role;Signal Transduction;Structure;System;Testing;therapeutic protein;Thinness;three dimensional cell culture;Time;Tissue Engineering;Tissues;Tooth structure;transcriptome;transglutaminase 2

PROJECT_TITLE: Enamel biomineralization; the role of pH cycling

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]


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

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Dogs are outbred companion animals that develop naturally occurring osteosarcoma in the setting of an intact immune system, allowing for comparative studies evaluating complex genetic interactions and the role of the immune and tumor microenvironment during progression and metastasis. This proposal seeks to build on extensive prior work in canine osteosarcoma biology and clinical trials to better understand the fundamental biology of naturally occurring osteosarcoma in dogs. Importantly, the proposed research will expand the utility of the canine and will identify cellular and molecular signatures to guide the futuredesign of canine osteosarcoma trials to improve translational impact and inform human trials aimed to improve outcomes in human patients with osteosarcoma.

PI_NAMEs: REBHUN, ROBERT B (contact)

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: Acceleration;Address;Adolescent;Alternative Therapies;Amputation;Biological Markers;Biology;canine model;Canis familiaris;Chemoresistance;chemotherapy;Child;Client;Clinical;clinical outcome measures;Clinical Trials;cohort;companion animal;comparative;Comparative Study;Complex;Cytotoxic Chemotherapy;Data;Data Commons;Data Set;Deposition;design;Disease;Disease Outcome;Disease Progression;effective therapy;Enrollment;Ensure;Future;Genetic;Genomics;high risk;Human;human disease;Immune;Immune system;Immunologics;improved;improved outcome;insight;Institution;Knowledge;Long-Term Survivors;Minority;Modeling;Molecular;Molecular Abnormality;Molecular Biology;Molecular Profiling;mouse model;Mus;Neoplasm Metastasis;novel therapeutics;oncology trial;Operative Surgical Procedures;Osteosarcoma;Outcome;Outcome Assessment;Patients;Pattern;Pharmaceutical Preparations;Platinum;Population;Population Control;Positioning Attribute;pre-clinical;Primary Neoplasm;prospective;Rare Diseases;Research;Resistance;Resources;Retrospective Studies;Role;screening;species difference;standard of care;success;Survival Rate;transcriptomics;translational impact;translational model;translational potential;trial design;tumor microenvironment;tumor-immune system interactions;Work

PROJECT_TITLE: Clinical, molecular, and immune characterization of naturally occurring osteosarcoma in dogs

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


NIH_SPENDING_CATS: Cancer;Cardiovascular;Heart Disease;Hematology;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Although the introduction of ponatinib, a third-generation tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myelogenous leukemia (CML) patients with T315I mutation, leading to a significant impact on overall survival and prognosis of patients, cardiotoxicity associated with ponatinib put the cancer survivors at a heightened risk of dying from heart failure instead. Several studies have linked that ponatinib-induced cardiotoxicity to impaired pro-survival signaling pathways leading to cell death, however, the molecular underpinning of these events is currently unknown making it difficult to efficiently counteract treatment-related adversities. Using human induced pluripotent stem cell-derived cardiomyocytes, an inducible cardiac-specific transgenic knockout and overexpression mouse, and CML mouse models, this research proposal aims to delineate novel molecular mechanisms responsible for ponatinib-induced cardiotoxicity and assess whether a small-molecule integrated stress response inhibitor (ISRIB) can mitigate undesirable outcomes of ISR activation on the heart without compromising the efficacy of ponatinib to limit cancer burden.

PI_NAMEs: LEE, WON HEE  (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Adenosine Triphosphate;Adult;Affect;Apoptotic;BCR gene;Binding;biological adaptation to stress;Cancer Burden;cancer cell;Cancer Patient;Cancer Prognosis;Cancer Survivor;Cardiac;Cardiac Myocytes;cardioprotection;Cardiotoxicity;Cardiovascular system;Cell Death;Cell Line;cell type;Cells;Chronic Myeloid Leukemia;chronic myeloid leukemia cell;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complement;Complex;Coupled;Couples;Data;Defect;Distress;Effectiveness;EIF-2alpha;Event;extracellular;FDA approved;Gatekeeping;Generations;Genes;Heart;Heart failure;Heart Injuries;Human;human induced pluripotent stem cells;Impairment;improved;In Vitro;in vivo;Individual;induced pluripotent stem cell;induced pluripotent stem cell derived cardiomyocytes;Induction of Apoptosis;inhibitor;Injury;innovation;insight;Intervention;K-562;Knock-out;knockout gene;Knowledge;Link;Maintenance;Malignant Neoplasms;Mediating;Mitochondria;mitochondrial dysfunction;Modeling;Molecular;molecular targeted therapies;mortality;mouse model;Mus;Mutation;Myocardial dysfunction;Names;neoplastic cell;novel;Oncology;Outcome;overexpression;Oxidation-Reduction;Oxidative Stress;Pathogenicity;Pathology;Pathway interactions;patient prognosis;Patients;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;Play;Prevalence;protective effect;Protein Biosynthesis;proteostasis;Reactive Oxygen Species;Research Proposals;Resistance;Risk;Role;Signal Pathway;Signal Transduction;small molecule;Stress;Study models;success;systemic toxicity;Therapeutic;therapeutic target;Time;tool;Toxic effect;Transgenic Organisms;Treatment Efficacy;Treatment-Related Cancer;tumor;tumor progression;Tyrosine Kinase Inhibitor;Up-Regulation

PROJECT_TITLE: Mitochondrial Dysfunction Underlies the Integrated Stress Response Activation in Ponatinib-Induced Cardiotoxicity

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE This study proposes to examine the role of Oxidation resistance 1 (Oxr1) in the development and progression of Parkinson's disease (PD) and Lewy Body Dementia (DLB) using rodent models of α-synucleinopathy. The study will improve our understanding of Oxr1-mediated neuroprotective pathways observed in PD and DLB to identify the new target(s) for therapeutic intervention.

PI_NAMEs: THOMAS, BOBBY  (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Affect;alpha synuclein;Autophagocytosis;Biochemical;biological adaptation to stress;C-terminal;Catalytic Domain;Cell Nucleus;Cell Survival;cell type;Cells;Clinical;Complement;Corpus striatum structure;Cytoplasmic Inclusion;Data;Defect;Dementia with Lewy Bodies;Development;Disease;disease model;DNA;dopaminergic neuron;Economics;Escherichia coli;Etiology;Exhibits;Functional disorder;Genes;Genome;Glucosyltransferases;Goals;GTP Phosphohydrolase Activators;Heme;Hippocampus;Homeostasis;Human;human data;Impaired cognition;Impairment;improved;in vivo;Inflammatory;innovation;insight;Intervention;Knowledge;Length;Lewy Bodies;Lewy Body Dementia;lysin;Lysine;Mediating;Mediator;Metabolism;mitochondrial dysfunction;Modeling;Molecular;Molecular Target;Motor;motor behavior;motor symptom;mouse model;Movement Disorders;Mus;mutant;myotubularin;Nerve Degeneration;neural network;Neurocognitive;Neurocognitive Deficit;Neurodegenerative Disorders;neuroinflammation;Neuronal Dysfunction;neuronal survival;Neurons;neuropathology;neuroprotection;new therapeutic target;novel;novel therapeutic intervention;Onset of illness;overexpression;oxidation;Oxidation-Reduction;Oxidative Phosphorylation;Oxidative Stress;Parkinson Disease;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;Phenotype;pre-clinical;Pre-Clinical Model;pre-formed fibril;Process;Prosencephalon;protective pathway;Proteins;Proteomics;Proton Pump;Quality Control;Quality of life;Regulation;repaired;Resistance;response;Rodent Model;Role;Signal Transduction;single nucleus RNA-sequencing;synucleinopathy;Systems Biology;Testing;Therapeutic;Therapeutic Intervention;transcriptomics;Transgenic Organisms;USP6 gene;vacuolar H+-ATPase;Wild Type Mouse

PROJECT_TITLE: Molecular Mechanisms of Oxidation Resistance 1 in Parkinson's disease and Lewy Body Dementia

STUDY_SECTION: CDIN

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: The neuronal aggregation of alpha-synuclein is deeply connected to Parkinson’s Disease and Alzheimer’s Disease Related Dementias. We recently uncovered an entirely new mechanism of alpha-synuclein toxicity in neurons, through modulation of mRNA. We will now systematically assess how important this is across a range of neuronal models and postmortem brain samples, examine why certain mRNAs are more perturbed in synucleinopathy, and determine key enzymes in the pathway that may be prospective therapeutic targets.

PI_NAMEs: KHURANA, VIKRAM  (contact)

PROGRAM_OFFICER_NAME: SWANSON-FISCHER, CHRISTINE R

PROJECT_TERMS: Affect;alpha synuclein;Alzheimer's disease related dementia;Autopsy;Binding;Biological Assay;Biology;Body Composition;Brain;Cellular Membrane;clinically significant;Complex;CRISPR interference;CRISPR/Cas technology;Cytoplasmic Granules;Cytosol;Data;decapping enzyme;Dementia with Lewy Bodies;Disease;dopaminergic neuron;Enzymatic Biochemistry;Enzymes;Exonuclease;experimental study;Functional disorder;Gene Expression Regulation;Genes;Genetic;genetic analysis;Homeostasis;Human Genetics;human induced pluripotent stem cells;Impaired cognition;In Vitro;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Investigation;knock-down;Knowledge;Lead;Left;Lesion;Lewy Bodies;Lewy Body Dementia;Lewy Body Disease;Link;Maps;Measures;Membrane;Membrane Proteins;Messenger RNA;Metabolism;model organism;Modeling;mouse model;mRNA decapping;mRNA Decay;Mutation;Nerve Degeneration;Neurons;neurotoxicity;novel;novel therapeutic intervention;Parkinson Disease;Parkinson's Dementia;Pathogenesis;Pathology;Pathway Analysis;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Physiological;Point Mutation;prevent;prospective;protein aggregation;Protein Biosynthesis;protein function;protein transport;Proteins;Publications;reconstitution;Research;response;Ribonucleoproteins;Risk;RNA;RNA Interference;RNA-Binding Proteins;Role;Sampling;scaffold;SNCA gene;sporadic Parkinson's Disease;Surveys;synucleinopathy;System;tau Proteins;Testing;therapeutic target;Toxic effect;trafficking;Transcript;translation factor

PROJECT_TITLE: Investigating physiologic and pathophysiologic connections between the Parkinson's disease protein alpha-synuclein and RNA binding proteins

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Disability Research;Headaches;Mental Health;Mental Illness;Migraine;Neurosciences;Pain Research;Rehabilitation;Telehealth

ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: DETAILED DESCRIPTION Migraine is a common, painful and disabling disorder; depressive symptoms are often comorbid with in people with migraine and increase suffering. The goal of this project is to evaluate the fidelity, feasibility, and acceptability of remote-delivered (telephone and video) mindfulness-based cognitive therapy (MBCT) for migraine disability and depressive symptoms. We will use pre-specified decision rules to determine study design for a future phase III clinical trial of remote-delivered MBCT.

PI_NAMEs: SENG-TAMACCIO, ELIZABETH K;SHALLCROSS, AMANDA J (contact)

PROGRAM_OFFICER_NAME: BAUMGARTNER, JENNIFER NICOLE

PROJECT_TERMS: Abbreviations;Absenteeism at work;acceptability and feasibility;Address;Adherence;Area;arm;associated symptom;Behavioral;Certification;Chronic;Chronic Disease;chronic pain;chronic painful condition;Classification;Client satisfaction;Clinical;Code;common symptom;comorbidity;Competence;Comprehension;Data;depressive symptoms;design;Development;disability;Disabling;Disease;Economic Burden;Emotional;evidence base;Feasibility Studies;Feedback;Future;Genetic;Goals;Guidelines;Headache;Headache disability;Headache Disorders;Health;Health Services Accessibility;High Prevalence;Home;Hour;Hypertension;improved;Individual;innovation;Integrative Therapy;International;intervention delivery;Interview;Knowledge;Length;Light;Manuals;Measures;Medical Care Costs;Mental Depression;Mental Health;Migraine;Migraine disability;migraine treatment;Mind-Body Intervention;mindfulness based cognitive therapy;National Center for Complementary and Integrative Health;Nausea;Neurobiology;New York;Occupational;opioid therapy;Pain;pain symptom;Participant;Pathway interactions;patient engagement;Patients;Persons;Phase;Phase III Clinical Trials;phase III trial;pleasure;primary outcome;Procedures;Productivity;Protocols documentation;Questionnaires;Randomized, Controlled Trials;recruit;remote delivery;Reporting;Research Design;Research Personnel;retention rate;Site;social;sound;Specific qualifier value;Standardization;symposium;Telephone;telephone based;telephone delivery;telephone session;Therapeutic;therapy development;Training;treatment arm;treatment as usual;United States National Institutes of Health;video delivery;Videoconferencing;Vomiting

PROJECT_TITLE: Feasibility and Acceptability of Telephone-delivered MBCT for Migraine and Depression (FATE-MD)


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

PHR: PROJECT NARRATIVE Cerebrospinal fluid flow plays an essential role in brain’s waste clearance system, and disrupted CSF flow is implicated in Alzheimer's disease. The goal of this project is to obtain previously unavailable knowledge on brain- wide CSF flow dynamics and pathways in the human brain using novel MR imaging technologies, and investigate the alteration of CSF flow in aging and in Alzheimer's disease, particularly its correlation with neuropathological protein depositions in AD patients, laying the foundation for future studies to discover CSF-flow-based imaging biomarkers and therapeutic interventions for Alzheimer's disease.

PI_NAMEs: DONG, ZIJING  (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: aged;Aging;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease related dementia;Amyloid beta-Protein;Animals;Arachnoid mater;Area;Automobile Driving;Blood Vessels;Brain;Brain imaging;Brain Mapping;Cardiac;career;career development;Cerebrospinal Fluid;cerebrospinal fluid clearance;cerebrospinal fluid flow;Circulation;Clinical;Communities;Data;Deposition;Elderly;Flowmetry;Foundations;Functional Magnetic Resonance Imaging;Future;General Hospitals;glymphatic system;Goals;Grant;healthy aging;Human;human study;Image;imaging biomarker;Imaging Device;imaging modality;Imaging Techniques;Imaging technology;Impairment;improved;innovation;Investigation;Knowledge;Link;Magnetic Resonance Imaging;Maps;Massachusetts;Measurement;Measures;Mentors;Methodology;Methods;Modeling;Morphologic artifacts;Motion;multidisciplinary;Nerve Degeneration;neural;Neurodegenerative Disorders;neuroimaging;neuropathology;new therapeutic target;non-invasive imaging;novel;Outcome;Outcome Study;Participant;Pathogenesis;Pathway interactions;Patients;Physics;Physiologic pulse;Physiology;Play;Positron-Emission Tomography;Process;programs;Proteins;Protocols documentation;Research;Research Personnel;research study;Resolution;Resources;Respiration;Role;Scanning;signal processing;Signal Transduction;skills;Spatial Distribution;spatiotemporal;Specificity;Subarachnoid Space;System;tau aggregation;tau Proteins;Techniques;Technology;Testing;therapeutic development;Therapeutic Intervention;Time;tool;Training;Translating;Translational Research;Transportation;wasting;Work

PROJECT_TITLE: Imaging brain-wide subarachnoid and perivascular cerebrospinal fluid flow in aging and Alzheimer's disease

STUDY_SECTION_NAME: Career Development Facilitating The Transition to Independence Study Section[AGCD-1]


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Bioengineering;Cancer;Data Science;Genetics;Hematology;Human Genome;Lymphatic Research;Lymphoma;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Obesity;Rare Diseases

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Public Narrative No model organism has contributed more than the laboratory mouse to improving human health. This project will develop computational tools that will greatly accelerate the pace of genetic discovery using the many available murine genetic models for human disease. Also, the mechanism by which computationally identified murine genetic factors that cause two diseases (lymphoma and diabetes) that are major public health problems will be characterized.

PI_NAMEs: PELTZ, GARY A (contact)

PROGRAM_OFFICER_NAME: MIROCHNITCHENKO, OLEG

PROJECT_TERMS: Acceleration;Affect;Alleles;Amino Acid Sequence;Artificial Intelligence;Artificial Intelligence enhanced;Candidate Disease Gene;candidate identification;causal variant;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;computational pipelines;computerized tools;Data;Data Analyses;Data Set;Data Sources;Databases;Development;Diabesity;Diabetes Mellitus;Disease;disease model;disease phenotype;DNA Sequence Alteration;Engineering;Evaluation;Exhibits;Exons;Foundations;Generations;Genes;Genetic;Genetic Enhancement;Genetic Models;genetic variant;Genetic Variation;Genome engineering;genome wide association study;Genomics;graph neural network;Health;Healthcare;Hodgkin Disease;Homologous Gene;Human;human disease;human model;improved;Inbred Strain;Individual;innovation;Knock-in Mouse;Knock-out;knockout gene;Laboratory mice;Lymphoma;Machine Learning;Malignant Neoplasms;Maps;Measures;Methods;model organism;mouse genetics;mouse genome;mouse model;Mus;Network-based;novel;Obesity;Paper;Pattern;Phenotype;protein protein interaction;public database;Public Health;Publishing;Research;response;Tandem Repeat Sequences;Training;trait;Validation;Variant

PROJECT_TITLE: Enabling AI-based Mouse Genetic Discovery

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-C(56)R]


ADMINISTERING_IC: LM

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Rural Health;Social Determinants of Health

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: NARRATIVE Despite the dramatic health inequities faced by sexual and gender minority (SGM) individuals, there are a dearth of training opportunities in general, and especially in the Deep South. Over 4 years, we will develop and implement a one-year training program for graduate students pursuing careers in health research, GenderS (Education on Gender and Sex), to synthesize SGM health content, develop concrete advocacy skills, and facilitate transparent dialogues regarding the systems and structures that limit SGM experience in the Deep South. Led by a unique community-academic partnership, and refined by rigorous evaluation and strategically disseminated to have national reach, the GenderS program will demonstrate to future investigators in health research how leaders from diverse backgrounds can work together to improve SGM health.

PI_NAMEs: KAY, EMMA SOPHIA;MACCARTHY, SARAH  (contact)

PROGRAM_OFFICER_NAME: BARR, ELIZABETH ANNE

PROJECT_TERMS: Academic Training;Academy;Acquired Immunodeficiency Syndrome;Address;Adult;Advocacy;Advocate;Age;Alabama;Anxiety;Attention;Automobile Driving;Biological;career;cisgender;Cities;Civil Rights;cohort;Collaborations;Communities;community academic partnership;community engagement;community organizations;community partners;Complex;Country;Deep South;Degree program;design;Development;Discrimination;Education;Educational Curriculum;Educational process of instructing;end of life care;Endowment;Enrollment;ethnic diversity;Ethnic Origin;Evaluation;experience;Face;Faculty;Feedback;Funding;Future;Gender;Gender Identity;gender minority community;gender minority group;gender minority health;gender minority youth;Goals;graduate student;Grant;Health;Health care facility;health inequalities;Heterosexuals;high school;Hispanic;Home;Homelessness;human centered design;Human Rights;Hybrids;improved;Inequity;Institution;interest;Interview;junior high school;Knowledge;Learning;lens;Lesbian Gay Bisexual Transgender Queer;Lived experience;lonely individuals;Magic;Malignant Breast Neoplasm;Malignant neoplasm of anus;Malignant neoplasm of lung;member;Mental Depression;Mentors;Methods;online course;Outcome;Perception;Persons;Politics;Positioning Attribute;Primary Care;programs;Psyche structure;Public Health;Race;racial diversity;recruit;Research;Research Institute;Research Personnel;Research Training;Residencies;resilience;Risk;Role;rurality;sex;Sex Orientation;Sexual and Gender Minorities;sexual minority group;sexual minority youth;skills;social;social implication;social stigma;Social Work;Structure;Students;success;Suicide attempt;support tools;Surveys;System;Training;training opportunity;Training Programs;United States;United States National Institutes of Health;virtual;Voice;Wellness Center;Work

PROJECT_TITLE: Education on Gender and Sex

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


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Data Science;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: BLOOMINGTON

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: This project develops advanced computational analysis methods for magnetic resonance imaging of brain networks. It uses novel tractometry techniques and high-performance computing methods to create new tools that will be useful for studying the structure of the brain’s white matter, both in healthy and diseased populations. In addition, this project seeks to validate these methods and tools in existing publicly available human and non-human primate data.

PI_NAMEs: GARYFALLIDIS, ELEFTHERIOS  (contact)

PROGRAM_OFFICER_NAME: DUAN, QI

PROJECT_TERMS: Acceleration;Address;Adoption;Algorithmic Software;Algorithms;analytical method;Anatomy;Area;Axon;base;Basic Science;Behavior;Brain;Brain imaging;brain pathway;Brain region;brain research;Clinical;clinical application;clinical translation;cluster computing;Cognitive;Collection;Communities;Computer Analysis;Computer software;Computing Methodologies;connectome;connectome data;Data;Data Analyses;Data Set;Detection;Development;Diffusion;Diffusion Magnetic Resonance Imaging;digital imaging;Disease;Goals;Health;High Performance Computing;Hour;Human;human data;Image;image processing;improved;in vivo;Individual;Individual Differences;innovation;insight;interest;large datasets;large scale data;Libraries;Magnetic Resonance Imaging;Maps;Measures;method development;Methodology;Methods;Modernization;Motion;neural;Neuroanatomy;neuroimaging;Neurologic;Neurons;Neurosciences;next generation;nonhuman primate;novel;open source;Outcome;parallel computer;Pathway interactions;Performance;Phase;physical property;Play;Population;Predisposition;Process;Property;Pythons;Quality Control;Research;Research Methodology;Research Personnel;Resources;secondary analysis;Sensitivity and Specificity;Software Tools;Speed;Structure;Structure-Activity Relationship;Techniques;Technology;Time;Tissues;tool;tractography;Translating;Validation;white matter;Work

PROJECT_TITLE: Community-supported open-source software for computational neuroanatomy


NIH_SPENDING_CATS: Brain Disorders;Genetics;HIV/AIDS;Human Genome;Infectious Diseases;Mental Health;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Project Narrative In the United States, nearly half of all HIV infected individuals show neurocognitive defects despite effective anti- retroviral treatment suggesting potential widespread HIV infections that impact the CNS. We will test whether silent HIV infections in the brain become reactivated in response to inflammation and how they are regulated by a specific class of nuclear receptors using model systems derived from induced pluripotent stem cells and humanized mice. The availability of numerous clinically-effective brain-penetrant drugs targeting key microglial cell nuclear receptors will allow us to identify drug candidates with high therapeutic potential.

PI_NAMEs: CANNON, PAULA M;KARN, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: RAO, VASUDEV RAMACHANDRA

PROJECT_TERMS: Acetylation;Agonist;Antiinflammatory Effect;antiretroviral therapy;Astrocytes;Biological Assay;Biological Models;Brain;Cell Maturation;Cell model;Cells;Central Nervous System;Central Nervous System Infections;Characteristics;chromatin immunoprecipitation;Chromatin Structure;Clinical;Coculture Techniques;cohort;Collaborations;Complex;Defect;design;drug candidate;Drug Targeting;Environment;Enzymes;Epigenetic Process;epigenetic regulation;epigenetic silencing;epigenomics;Evaluation;Event;Exhibits;experimental study;Family;FDA approved;genetic manipulation;Genetic Transcription;Glucocorticoid Receptor;Glucocorticoids;Goals;Heterogeneity;histone methylation;histone modification;Histones;HIV;HIV Infections;HIV-1;HIV-associated neurocognitive disorder;Human;humanized mouse;IL13RA1 gene;Individual;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Infection;Inflammation;Inflammatory Response;Intervention;knock-down;Knock-out;Laboratories;Lead;Ligands;Maps;Measures;Mediating;member;Methods;Microglia;Modeling;Molecular Cloning;Monitor;mouse model;Mus;Neurocognitive;neuroinflammation;Neurons;Neuropathogenesis;neurotoxic;novel;novel therapeutic intervention;NR4A2 gene;Nuclear;Nuclear Receptors;Outcome;Patients;Pharmaceutical Preparations;pharmacologic;Phosphorylation;Physiology;Play;pre-clinical;programs;promoter;Promoter Regions;reactivation from latency;receptor;recruit;Refractory;Regulation;Resolution;response;RNA;Role;RXR;Sampling;single cell ATAC-seq;single cell sequencing;single cell technology;single-cell RNA sequencing;Symptoms;System;T-Lymphocyte;Testing;Therapeutic;transcriptome;Transformed Cell Line;Transgenic Mice;translatable strategy;United States;Variant;Vesicular stomatitis Indiana virus;Viral;Virus;Virus Replication;Work

PROJECT_TITLE: Nuclear receptor regulation of epigenetic mechanisms regulating HIV CNS latency


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Bioengineering;Biotechnology

ORG_CITY: Santa Clara

ORG_NAME: CYTORUM, INC.

PHR: Narrative  Flow cytometry is a powerful analysis platform that is capable of measuring dozens of characteristics of single cells within complex populations of cells. In this grant, we propose to further develop a technology that can greatly increase the number of proteins that can be measured by flow cytometry, focusing on developing markers for T cells, which play an essential role in the immune system's response to pathogens, in diseases such as autoimmunity, and more recently in the fight against cancer.

PI_NAMEs: KRUTZIK, PETER  (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: Acrylamides;Antibodies;Antigens;Area;Attention;Autoimmune Diseases;Autoimmunity;Biological Assay;biomarker discovery;Blood;Blood specimen;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Compartmentation;Cell Surface Proteins;cell type;Cells;Cellular biology;Characteristics;Classification;Clinical Trials;Complex;Cryopreservation;Cytometry;data acquisition;Data Set;Development;differential expression;Disease;Disease Progression;Encapsulated;exhaust;experimental study;fighting;Flow Cytometry;Freezing;Genomics;Grant;Human;human disease;Human Pathology;Hydrogels;Immune response;Immune system;Immunologics;Immunology;Immunooncology;Industry;Malignant Neoplasms;Mass Spectrum Analysis;Measures;Mediating;Methods;Modernization;Nature;next generation;novel;novel marker;pathogen;Pathology;performance tests;Peripheral Blood Mononuclear Cell;Phase;phase 1 study;phase 2 study;Phase I Clinical Trials;Phenotype;Play;Population;Process;programs;Protein Analysis;protein biomarkers;Proteins;Proteome;Proteomics;Protocols documentation;Qualifying;Reagent;Regulatory T-Lymphocyte;Reproducibility;Research;Resolution;response;Rest;Role;Running;Sampling;Scientist;Services;single cell analysis;single cell proteins;Speed;Stains;success;Surface;System;T memory cell;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Therapeutic;tool;transcriptomics;Treatment Efficacy;Western Blotting;Whole Blood;Work

PROJECT_TITLE: Proteome Capture in Hydrogel Beads for High Resolution Single Cell Analysis


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Emerging Infectious Diseases;Genetics;Infectious Diseases;Rare Diseases

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative: In the life cycle of the human oncogenic virus Kaposi’s sarcoma-associated herpesvirus, the expression of key viral lates genes is dependent on replication of the viral genome. Here, we propose to use a variety of functional genomics methods to discover the viral proteins, viral DNA regulatory regions, and functional host interactors that maintain this dependency. Together, these will allow us to develop and test new models for this key therapeutic target in this human oncovirus.

PI_NAMEs: MORGENS, DAVID W (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Affect;Automobile Driving;Binding;Biological;Cancer Etiology;Cells;CRISPR/Cas technology;Data;Dependence;DNA;DNA biosynthesis;DNA-Directed DNA Polymerase;DNA-Directed RNA Polymerase;Double Stranded DNA Virus;ds-DNA;Elements;Essential Genes;Event;functional genomics;gammaherpesvirus;Gene Expression;Genes;Genetic;Genetic Transcription;Genome;Genomic approach;Genomic Instability;Herpesviridae;Human;human DNA;Human Herpesvirus 8;Immunocompromised Host;Individual;Infection;Integration Host Factors;Knowledge;Late Gene Transcriptions;Life Cycle Stages;Link;Lytic;lytic replication;Malignant Neoplasms;Measures;Methods;Modeling;Molecular;Mutagenesis;mutant;Mutation;Nucleic Acid Regulatory Sequences;Oncogenic;Oncogenic Viruses;Oncornaviruses;particle;Pathogenicity;Patients;Phenotype;Play;Postdoctoral Fellow;prevent;Process;Proteins;Regulatory Element;Replication Origin;RNA;Role;Testing;Therapeutic;therapeutic target;Transcription Coactivator;transcription factor;Viral;viral DNA;Viral Genes;Viral Genome;Viral Proteins;Virion;Virus;Virus Diseases;virus genetics;Virus Replication;Work

PROJECT_TITLE: Separating late gene transcription from viral DNA replication in KSHV

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Advisory Committee[MID]


ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Skeletal muscle is the largest insulin-sensitive tissue and a major regulator of metabolic homeostasis in the human body. Human variants in the cytoskeletal protein ankyrin-B, highly expressed in skeletal muscle, lead to ankyrin-B deficiency and metabolic disease. This project will determine how ankyrin-B deficiency in skeletal muscle leads to altered skeletal muscle energetic and metabolic capacity via its association with mitochondria. These studies are essential to understand mitochondrial physiology and the development of skeletal muscle and metabolic diseases.

PI_NAMEs: VOOS, KAYLEIGH MARIE (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: age related;Aging;ANK2 gene;Binding;Biochemical;Bioenergetics;Biogenesis;Biological;Biological Assay;Calcium;Cardiometabolic Disease;Cardiovascular Diseases;Cell Adhesion Molecules;Cell Respiration;cell type;Cells;Cellular biology;Complement;Complex;cost;Cytoskeletal Proteins;Cytoskeleton;Data;Deficiency Diseases;defined contribution;Diabetes Mellitus;Disease;Dissociation;Endoplasmic Reticulum;endurance exercise;energy balance;Exercise;exercise capacity;Exhibits;extracellular;flexibility;Genetic Transcription;genetic variant;genome editing;Glucose;Goals;Health;Homeostasis;Human;Human body;Human Genetics;Impairment;in vivo;inorganic phosphate;Inositol;insight;Insulin;insulin regulation;insulin sensitivity;Ion Channel;ITPR1 gene;Knock-in Mouse;Knockout Mice;Label;Lead;Link;Measures;Membrane Microdomains;Membrane Transport Proteins;Metabolic;Metabolic Diseases;Metabolism;Microscopy;Mitochondria;Molecular;mouse model;Mus;Muscle Cells;Muscle Fibers;Myopathy;Nature;Neurons;Non obese;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Organ;Organelles;Oxygen Consumption;Pathway interactions;Physiological Processes;Physiology;Positioning Attribute;Production;Proteins;Publishing;receptor;Regulation;release of sequestered calcium ion into cytoplasm;Reporting;Resolution;Respiration;Risk Factors;Role;Signal Transduction;Site;Skeletal Development;Skeletal Muscle;skeletal muscle metabolism;Stress;stressor;Structure;superresolution microscopy;Techniques;Testing;Tissues;Training;Translating;Transmission Electron Microscopy;ultra high resolution;Variant;western diet;Work

PROJECT_TITLE: A mechanism of skeletal muscle ER-mitochondria interaction and bioenergetics modulation

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


ORG_CITY: FAYETTEVILLE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE

ORG_STATE: AR

PHR: Project Narrative Exercise is a powerful stimulus for attenuating age-associated tissue decline, but the molecular mechanisms behind this are incompletely understood. Using muscle functional, bioenergetic, and cellular measures as well as nucleus-specific DNA methylation aging analysis and single myonuclear RNA-sequencing, the purpose of this proposal is to provide fundamental information on what mediates skeletal muscle molecular reprogramming toward youthfulness. Combined with a conditional and inducible muscle-specific gene expression model and a new murine exercise training approach, we hypothesize that the exercise-responsive Yamanaka factor MYC plays a central role in promoting a youthful tissue profile during aging and can be leveraged to improve muscle health throughout the lifespan.

PI_NAMEs: MURACH, KEVIN  (contact)

PROGRAM_OFFICER_NAME: BOYCE, AMANDA T

PROJECT_TERMS: Acute;Adult;Affect;Age;age effect;Age Months;age related;age related decline;Aging;aging clocks;Bioenergetics;biological age;Biological Aging;c-myc Genes;Cell Nucleus;Cells;Characteristics;cost;DNA;DNA Methylation;DNA Methylation Regulation;Dose;Doxycycline;Elderly;endurance exercise;enhancing factor;epigenetic aging;epigenetic clock;Epigenetic Process;epigenome;Euthanasia;Exercise;exercise training;experimental study;Extracellular Matrix;Female;Fiber;Foundations;functional decline;functional mimics;Gastrocnemius Muscle;Gene Expression;Gene Expression Profile;Genetic Transcription;Genome;genome wide methylation;Health;healthspan;Hindlimb;Histologic;Human;improved;In Vitro;in vivo;injury recovery;innovation;Knowledge;Label;late life;Life;Life Expectancy;life span;male;Measures;Mediating;Mediator;Metabolic;methylation pattern;methylome;Modeling;Molecular;mouse model;Mus;Muscle;muscle aging;Muscle Fibers;muscle form;Muscle function;muscle progenitor cell;Myosin ATPase;novel;Nuclear;old mice;overexpression;Periodicals;Phenotype;Physical Function;Physiologic pulse;Plantaris muscle;Play;Population;Process;Regulation;Rejuvenation;Reporting;Research;Resistance;resistance exercise;Resolution;Role;Running;sedentary;senescence;senescent cell;Shapes;Skeletal Muscle;Soleus Muscle;Spirometry;Stimulus;Testing;Time;Tissues;transcriptome;transcriptome sequencing

PROJECT_TITLE: Mediators of Muscle Rejuvenation with Aging

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