NIH_SPENDING_CATS: HIV/AIDS;Immunization;Immunotherapy;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative T cells control infections and cancer, but prolonged stimulation can result in T cell dysfunction and senescence which allows disease progression. This proposal will demonstrate how T cells can avoid dysfunction and senescence and undergo indefinite proliferation while retaining function and longevity. Outcomes of the proposal will inform vaccination, T cell engineering, and adoptive cell therapies for infectious and malignant disease.

PI_NAMEs: MASOPUST, DAVID  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Acute;Address;Adoptive Cell Transfers;Affinity;Antigens;Cancer Control;CD8-Positive T-Lymphocytes;Cell division;Cell Maintenance;Cells;Cellular biology;Cessation of life;Chronic;Chronic Disease;chronic infection;Chronology;Clinical;Clonal Expansion;Clone Cells;cohort;cytokine;Cytoprotection;Data;Disease;Disease Progression;engineered T cells;Engineering;Environment;exhaustion;Exhibits;Experimental Designs;fitness;Frequencies;Functional disorder;Goals;Grant;Immunity;Immunize;Immunologic Memory;Immunology;immunomodulatory therapies;immunoregulation;Immunotherapy;Impairment;in vivo;Infection Control;Learning;Longevity;Malignant - descriptor;Malignant Neoplasms;Mucous Membrane;Mus;Nutritive Value;Organism;Outcome;pathogen;Population;preservation;prevent;Process;Proliferating;proliferation potential;Proteins;Resistance;response;Rest;Sampling;senescence;stem cells;T cell differentiation;T cell regulation;T memory cell;T-Cell Receptor;T-Lymphocyte;targeted treatment;Testing;therapy development;tool;Vaccination;vaccine development;Work

PROJECT_TITLE: Mucosal T cell memory to pathogens

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Genetics;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: MILWAUKEE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: PROJECT NARRATIVE In autoimmune diabetes, a person’s immune system kills insulin-producing beta cells in the pancreas, which makes the pancreas unable to produce insulin to control blood sugar levels. The reasons people develop autoimmune diabetes are not entirely known, but the cause goes beyond a family history of diabetes. This proposal aims to determine how specific beta cell proteins control changes in genetic programs that promote beta cell health or disease and to create new drugs and cells that promote beta cell health.

PI_NAMEs: SMITH, BRIAN CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: SPAIN, LISA M

PROJECT_TERMS: Acetylation;Adverse effects;Antiinflammatory Effect;Attenuated;attenuation;Autoimmune Diabetes;Autoimmune Diseases;autoimmune inflammation;Beta Cell;beta cell replacement;Binding;Biochemical;Blood Glucose;BRD2 gene;Bromodomain;Bromodomains and extra-terminal domain inhibitor;Cell Differentiation process;Cell Line;Cell Physiology;cell type;Cells;Chromatin;Cytoprotection;Data;Defect;Development;Diabetes Mellitus;Diabetic mouse;Disease;Dose Limiting;Drug Delivery Systems;Drug Targeting;endocrine pancreas development;Enhancers;Epigenetic Process;epigenomics;Family history of;Family member;Fatigue;fetal;gastrointestinal;Genes;Genetic;Genetic Engineering;Genetic Transcription;Goals;Health;Histone Acetylation;Histones;human induced pluripotent stem cells;Immune system;immune system function;improved;Inbred NOD Mice;Individual;Inflammation;Inflammatory;inhibitor;innovation;Insulin;Insulin deficiency;Insulin-Dependent Diabetes Mellitus;islet;islet stem cells;Knock-out;Learning;Lysine;Memory;Methods;mouse model;next generation;Non obese;novel therapeutics;overexpression;Pancreas;Persons;Phenotype;Preparation;prevent;programs;promoter;Proteins;Publishing;Reader;Research;response;Role;side effect;Structure of beta Cell of islet;T-Lymphocyte;Testing;therapeutic effectiveness;Toxic effect;transcription factor;transcriptomics;type I diabetic

PROJECT_TITLE: Biochemical mechanisms of beta cell protection through bromodomain inhibition

STUDY_SECTION: BMDM

STUDY_SECTION_NAME: Basic Mechanisms of Diabetes and Metabolism Study Section[BMDM]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Diabetes;Eye Disease and Disorders of Vision;Neurosciences;Prevention

ORG_CITY: NEW YORK

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE  In the retina, vascular endothelial growth factor (VEGF) production is induced in response to hypoxia or ischemia and is considered the key agent responsible for neovascularization in diabetic retinopathy (DR). The proposed work aims to improve anti-VEGF treatment evaluation in DR by 1) improving our understanding of how retinal vascular structures and perfusion relate to DR severity and 2) develop valid, reliable and objective measures for evaluating treatment response. As novel therapeutic agents for DR continue to emerge, this data is urgently needed to help personalize choices and tailor dosing of therapies to the individual patient with DR.

PI_NAMEs: CHUI, YUEN PING TOCO (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: adaptive optics;Address;Age;American;Angiography;Area;Biological;Biological Markers;Blindness;Blood capillaries;Blood Cells;Blood Vessels;Categories;Cell Density;Clinical;Clinical assessments;Clinical Data;Clinical Trials;Computer software;contrast imaging;Custom;Data;Data Collection;Databases;density;design;Detection;Diabetic Retinopathy;Dose;Early Diagnosis;Engineering;Erythrocytes;Evaluation;Event;Funding;Goals;Hypoxia;Image;Image Analysis;image processing;Imaging Techniques;improved;Individual;individual patient;Injections;inter-individual variation;Intervention;Ischemia;Knowledge;Light;Maps;Measurable;Measurement;Measures;Methods;Microaneurysm;Monitor;neovascularization;novel strategies;novel therapeutics;Ophthalmology;Ophthalmoscopes;Ophthalmoscopy;Optical Coherence Tomography;Optics;Outcome;Patients;Perfusion;prevent;Production;proliferative diabetic retinopathy;prospective;Prospective, cohort study;quantitative imaging;Race;Reference Values;Reperfusion Therapy;Resolution;response;Retina;Retinal Diseases;retinal imaging;retinal ischemia;Scanning;Severities;Severity of illness;sex;Structure;Therapeutic Agents;Time;time interval;Treatment Efficacy;Treatment Factor;treatment response;Uncertainty;Vascular Diseases;Vascular Endothelial Growth Factors;vasoconstriction;Visual Acuity;Visual impairment;Visualization;Work

PROJECT_TITLE: Characterization of vascular responses to intravitreal anti-VEGF injections in diabetic retinopathy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 NV-P (81)]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: BIRMINGHAM

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: One of the indicators of poor prognosis in T-cell acute lymphoblastic leukemia (T-ALL) is extramedullary infiltration of leukemic cells to the CNS/meninges. We propose to study how T-ALL cells exploit pro- inflammatory pathway to facilitate meningeal infiltration. The identification of the mechanism by which leukemic cells form a supportive niche in the meninges will lead to novel targets for future therapies.

PI_NAMEs: MATLAWSKA-WASOWSKA, KSENIA  (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Acute Lymphocytic Leukemia;Acute T Cell Leukemia;acute T-cell lymphoblastic leukemia cell;Address;Adopted;Affect;Animal Model;Automobile Driving;Cell Culture System;Cell Lineage;cell motility;Cells;Central Nervous System;Central Nervous System Diseases;Central Nervous System Leukemia;Cerebrospinal Fluid;chemokine;chemokine receptor;Chemotaxis;Child;Childhood Leukemia;CXCL10 gene;CXCR3 gene;cytokine;Data;Development;Diagnosis;Disease-Free Survival;Encephalitis;Extramedullary;Future;Goals;Hematologic Neoplasms;high risk;Immunocompetent;improved;Infiltration;Inflammation Mediators;Inflammatory;insight;Invaded;leukemia;Leukemic Cell;Leukemic Infiltration;Leukocytes;Mediating;Mediator;Meningeal;Meninges;Meningitis;Microfluidics;migration;Modeling;Morbidity - disease rate;mouse model;Mus;neuroinflammation;novel;novel therapeutics;Pathway interactions;patient derived xenograft model;patient prognosis;Patient-Focused Outcomes;Patients;pediatric patients;Pericytes;Phenotype;Play;Prognosis;Prognostic Factor;Prognostic Marker;Property;Relapse;Research;response;risk stratification;Role;Signal Pathway;Signal Transduction;Site;Solid Neoplasm;Survival Rate;T-Lymphocyte;TAL1 gene;targeted treatment;Testing;Therapeutic;three dimensional cell culture;TNF gene;trafficking;Treatment Failure;Tropism;Up-Regulation

PROJECT_TITLE: Role of CXCR3-CXCL10 signaling in T-ALL CNS disease

STUDY_SECTION: TEHM

STUDY_SECTION_NAME: Tumor Evolution, Heterogeneity and Metastasis Study Section[TEHM]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Estrogen;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Menopause;Mental Health;Mental Illness;Neurosciences;Prevention;Serious Mental Illness;Sleep Research;Women's Health Research

ORG_CITY: LA JOLLA

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Narrative The purpose of this study is to investigate the biological basis of mood, sleep and energy (activity) disturbances in women undergoing the menopausal transition, examine whether disruption in circadian rhythms measured by melatonin underlies these disturbances, and determine whether critically-timed sleep and light treatments administered in home environments can correct the biological rhythm dysregulation, and thereby improve mood, sleep and activity, enhancing health and well-being and preventing further dysfunction and disability.

PI_NAMEs: PARRY, BARBARA L (contact)

PROGRAM_OFFICER_NAME: LYONS, ELIZABETH ANNE

PROJECT_TERMS: 6-sulfatoxymelatonin;abeta deposition;actigraphy;Address;affective disturbance;Aging;aging brain;Alzheimer's disease risk;Award;Basic Science;Biological;Biological Rhythm;Cardiovascular system;circadian;Circadian Dysregulation;Circadian Rhythms;Clinical;Cognitive;cost;Data;Depressed mood;depressed patient;depressive symptoms;design;disability;Disease;disorder prevention;Diurnal Rhythm;Estradiol;Female;Functional disorder;functional improvement;Future;global health;Goals;Health;health disparity;Home;Home environment;Hormonal;Hormonal Change;Hospitals;Hour;Human;immune function;Impairment;improved;Individual;innovation;Intervention;Investigation;Light;Longevity;Major Depressive Disorder;Malignant Neoplasms;Measures;Mediator;Medicine;Melatonin;Mental Depression;Mental Health;Metabolic;middle age;Modeling;Mood Disorders;Moods;mortality;Nobel Prize;novel;Osteoporosis;Ovarian;Participant;Perimenopause;Periodicity;peripartum depression;Personal Satisfaction;Phase;Phototherapy;Physical activity;physical conditioning;Physiology;Plasma;Polysomnography;Population;prevent;Preventive Medicine;Progesterone;Psychometrics;Psychoses;Randomized;Recurrence;Reduce health disparities;Regulation;Reporting;response;restoration;Risk;Scientist;Severities;Sleep;Sleep Disorders;Sleep disturbances;Sleeplessness;stress reactivity;Suicide;symptomatic improvement;Symptoms;targeted treatment;tau-1;Testing;Therapeutic;therapy design;Time;Translating;treatment optimization;Treatment outcome;treatment response;Underserved Population;urinary;Woman;Work

PROJECT_TITLE: Chronobiological Basis of Depression during the Menopause Transition

STUDY_SECTION: NPAS

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Hematology;Neurosciences;Nutrition;Pediatric;Women's Health Research

ORG_CITY: SAINT LOUIS

ORG_DEPT: PEDIATRICS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Adolescent females who develop iron deficiency anemia are at higher risk for strokes and decreased school performance than non-anemic peers. This study will use MRI to examine potential mechanisms of reversible and irreversible neurocognitive effects of late-childhood iron deficiency anemia in females ages 12-21 years, and may lead to changes in screening practices in order to optimize health and cognitive performance in the developing brain.

PI_NAMEs: FIELDS, MELANIE ERIN (contact);GUILLIAMS, KRISTIN

PROGRAM_OFFICER_NAME: GILLASPY, ALLISON

PROJECT_TERMS: 21 year old;Acute;Adult;Age;Anemia;Attention;Blood;Brain;brain health;brain magnetic resonance imaging;career;Cerebrovascular Circulation;Cerebrum;Child;Childhood;Clinical;clinically relevant;Cognition;Cognitive;cognitive ability;cognitive function;cognitive performance;cognitive testing;comparison control;Compensation;Data;Development;Diagnosis;Disease;early childhood;Education;Enrollment;Evaluation;executive function;experience;Failure;falls;Female;Female Adolescents;Foundations;Functional disorder;Future;Goals;Health;Hemoglobin;High Prevalence;high risk;Image;Impaired cognition;improved;Incidence;Infant;Infarction;innovation;Iron;Iron deficiency anemia;Knowledge;Late Effects;Life;Link;Magnetic Resonance Imaging;Measures;Menstruation;Metabolic;metabolic rate;Metabolic stress;Metabolism;Nervous System Trauma;Neurocognitive;Neurocognitive Deficit;neurodevelopment;neuroimaging;Neurologic;Neurologic Dysfunctions;Outcome;Oxygen;Participant;peer;Performance;Persons;Population;prevent;prospective;Recommendation;Reporting;Resolution;Risk;Schools;screening;screening guidelines;Secondary to;sex;Sickle Cell Anemia;stroke risk;Structure;Subgroup;Symptoms;Techniques;Testing;Time;Toddler;Transfusion;treatment optimization;United States;white matter;Work;years lived with disability;young woman

PROJECT_TITLE: Neurocognitive Effects of Late-Childhood Iron Deficiency Anemia

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE:  Targeting neuroinflammation represents a promising therapeutic strategy for Alzheimer's disease. This work will investigate the potential of small molecules that target the microglial receptor TREM2 to alleviate neuroinflammation and reduce amyloid plaque deposition in animal models. Successful completion of this work has the potential to establish a new immunotherapeutic strategy for Alzheimer's disease focused on modulation of TREM2 function using small molecules.

PI_NAMEs: GABR, MOUSTAFA  (contact)

PROGRAM_OFFICER_NAME: GROTHAUS, PAUL G

PROJECT_TERMS: absorption;Affinity;Alzheimer's Disease;Alzheimer's disease therapeutic;Amyloid;Animal Model;Anti-Inflammatory Agents;Antibodies;antibody mimetics;Area;Binding;Binding Sites;Biological Assay;Biophysics;Blood - brain barrier anatomy;blood-brain barrier crossing;Brain;Calorimetry;Cells;Chemicals;Clinical Trials;computer studies;cytokine;Deposition;Distal;Dose;drug candidate;Drug Kinetics;Energy Transfer;Evaluation;Excretory function;familial Alzheimer disease;Fluorescence;Galectin 3;glial activation;Goals;Immune;immune function;immune-related adverse events;Immunotherapeutic agent;Impairment;In Vitro;in vivo;Inflammatory;inhibitor;innovation;Interferometry;Investigation;lead optimization;Libraries;Ligand Binding;Ligands;Maps;Mediating;Memory impairment;Metabolism;Microglia;mouse model;mutant;Mutation;nanomolar;neuroinflammation;novel;novel therapeutic intervention;Pathogenesis;Pathologic;Permeability;Phagocytosis;pharmacophore;Play;Positioning Attribute;Production;protein data bank;Protocols documentation;receptor;Receptor Cell;Reporting;Research;response;Role;screening;Senile Plaques;small molecule;small molecule inhibitor;small molecule libraries;Structure;success;Surface;Surface Plasmon Resonance;Temperature;Testing;Therapeutic;therapeutic target;Time;Titrations;TREM2 gene;virtual screening;Work

PROJECT_TITLE: Discovery of first-in-class small molecule TREM2 ligands as therapeutics for Alzheimer's disease

STUDY_SECTION: DMPB

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology B Study Section[DMPB]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Digestive Diseases;Immunotherapy;Inflammatory Bowel Disease

PHR: PROJECT NARRATIVE: Current therapeutic approaches for inflammatory bowel disease (IBD) have reached a plateau in the rates of response and/or remission. Overcoming this plateau requires the identification of rational combinations of therapies with complementary mechanisms of action. This work is focused on the preclinical validation of small molecule-based dual CD28/ICOS blockade as a new therapeutic strategy for IBD.

PROGRAM_OFFICER_NAME: NGUYEN, KHOA DINH DANG

PROJECT_TERMS: absorption;Address;Adverse event;adverse event risk;Affect;Affinity;analog;Animal Model;antagonist;Antibodies;antibody mimetics;Binding;Biological Assay;Biological Products;Biophysics;Cells;Chronic;Clinical;clinical translation;Clinical Trials;Colitis;Combined Modality Therapy;cytokine;Digestive System Disorders;Disease;Disease remission;Docking;Drug Kinetics;effective therapy;efficacy evaluation;Evaluation;Excretory function;Free Energy;Goals;human subject;Immune;Immune System Diseases;Immune Targeting;immunogenic;immunogenicity;Immunomodulators;immunoregulation;Immunotherapeutic agent;improved;In Vitro;in vivo;Incidence;Individual;Inflammatory;Inflammatory Bowel Diseases;inflammatory modulation;inhibitor;innovation;Integrins;Interleukins;Investigation;Investigational Drugs;Lead;lead optimization;Libraries;Life;Ligand Binding;Maps;Metabolism;Modeling;Molecular;mouse model;Mus;nanomolar;new combination therapies;novel strategies;novel therapeutic intervention;Pathogenesis;Pathway interactions;Patients;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;pharmacophore;Phase II Clinical Trials;Play;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;Proteins;Protocols documentation;Receptor Cell;Reporting;response;Risk;Role;Route;Sampling;screening;Severities;small molecule;small molecule inhibitor;Structure;success;Surface Plasmon Resonance;Systemic Lupus Erythematosus;T-Lymphocyte;targeted treatment;Temperature;Testing;Therapeutic;therapeutic evaluation;therapeutic protein;therapy outcome;TNF gene;Treatment Failure;treatment optimization;Validation;Work

PROJECT_TITLE: Optimization of small molecule immunomodulators as combination therapy for IBD

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


ED_INST_TYPE: SCHOOLS OF NURSING

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

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project narrative. Statistical methods to characterize patients who highly benefit from treatments on multiple clinical outcomes, are important for Alzheimer’s disease and other related dementias (ADRDs): such methods allow individual patients/physicians to choose a treatment if it is predicted to provide them multiple high benefits and minimal risks. However, accurate methods for multiple such goals do not exist. This work proposes to develop such methods for characterizing patients with multiple such benefits, by incorporating the clinical goals directly into the method construction process; and shows, with strong preliminary evidence, that the new methods can benefit an overwhelmingly larger group of patients than standard methods.

PI_NAMEs: FRANGAKIS, CONSTANTINE E (contact)

PROGRAM_OFFICER_NAME: HETTINGER, JANE CECELIA

PROJECT_TERMS: Address;Agitation;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;American;Benefits and Risks;Caregivers;Citalopram;Clinical;Cognitive;cognitive function;Dementia;design;Dimensions;disease heterogeneity;Disputes;Goals;Healthcare;improved;individual patient;innovation;Link;Methodology;Methods;minimal risk;Modeling;Modernization;neural;neural network;Observational Study;Outcome;outcome prediction;Patients;personalized medicine;Physicians;precision medicine;primary outcome;Primary Progressive Aphasia;Process;prototype;Randomized;randomized trial;Statistical Methods;Symptoms;Testing;transcranial direct current stimulation;treatment choice;Uncertainty;Work

PROJECT_TITLE: Statistical methods to characterize patients who highly benefit across multifaceted clinical outcomes, from treatments in Alzheimers Disease and Related Dementias (ADRD)

STUDY_SECTION: ASPA

STUDY_SECTION_NAME: Analytics and Statistics for Population Research Panel A Study Section[ASPA]


NIH_SPENDING_CATS: Aging;Cardiovascular;Estrogen;Orphan Drug;Rare Diseases;Women's Health Research

ORG_CITY: LEXINGTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Project Narrative Abdominal aortic aneurysm (AAA) is a severe vascular disease affecting millions of Americans. Women develop AAA less and later than men, but AAA in women is more aggressive, with more rapid expansion, a higher tendency to rupture, and higher mortality following rupture. This application aims to investigate the mechanisms that underlie AAA in female mice and to identify new therapeutic targets to develop new drugs to treat AAA.

PI_NAMEs: GONG, MING C;GUO, ZHENHENG  (contact)

PROGRAM_OFFICER_NAME: STABLEY, JOHN N

PROJECT_TERMS: Abdominal Aortic Aneurysm;Accounting;Affect;Aging;Aldosterone;American;Aneurysm;Animal Model;Animals;Antibodies;Aorta;Aortic Aneurysm;Atherosclerosis;Blocking Antibodies;Cell Nucleus;Cessation of life;circadian;Clinical Trials;Data;Diameter;Disease;Endothelial Cells;eplerenone;Estrogens;Exhibits;Female;Genes;Genetic;Goals;high risk;Hormone replacement therapy;hormone therapy;Human;Hypertension;ICAM1 gene;Infiltration;insight;Intercellular adhesion molecule 1;juvenile animal;Literature;male;men;Mineralocorticoid Receptor;Modeling;Molecular;Morality;Morbidity - disease rate;mortality;mouse model;Mus;Myeloid Cells;neutrophil;Neutrophil Infiltration;new therapeutic target;Nicotine;novel therapeutics;Nuclear Translocation;old mice;Older Population;Operative Surgical Procedures;Ovariectomy;Pathology;Pharmaceutical Preparations;Postmenopause;pre-clinical;Premenopause;Progesterone;receptor;receptor expression;repaired;Research;Risk Factors;Role;Rupture;salt intake;Scheme;sex;sexual dimorphism;Signal Transduction;Smoke;Smoking;Sodium Chloride;Stanolone;Testing;Therapeutic;United States;Up-Regulation;Vascular Diseases;Woman

PROJECT_TITLE: Targeting Endothelial Cell Mineralocorticoid Receptor Against Aortic Aneurysm in Females

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


NIH_SPENDING_CATS: Genetics;Human Genome;Lung

ORG_CITY: MOBILE

ORG_NAME: UNIVERSITY OF SOUTH ALABAMA

PHR: PROJECT NARRATIVE The contribution of oxidative mitochondrial (mt) damage to lung injury, repair, and remodeling is undisputed, but mechanisms underlying associations between mtDNA damage and these pathophysiological events remain to be elucidated. Moreover, despite the severity and prevalence of these debilitating conditions, there are no specific biomarkers or therapies available to facilitate diagnosis and treatment. Thus, the goal of this proposal is to test the transformative hypothesis that a signaling axis involving mtDNA repair and caspase-1 integrates processes essential for initiation and resolution of NLRP3-dependent inflammation, and leverage these findings towards discovery of novel targets to treat acute lung injury.

PI_NAMEs: AUDIA, JONATHON PETER;GILLESPIE, MARK N (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: Acute;Acute Lung Injury;Affect;analytical method;Attention;Attenuated;base;Base Excision Repairs;Biogenesis;C-terminal;CASP1 gene;Cell Death;Cells;Coupled;Cultured Cells;cytokine;Cytosol;Diagnosis;DNA biosynthesis;DNA glycosylase;DNA Repair Pathway;DNA Sequence;Ensure;Enzymes;Event;extracellular;Functional disorder;Generations;Genomics;Goals;Guanine;Inflammasome;Inflammation;Inflammatory;inflammatory lung disease;Inflammatory Response;Injury;innovation;insight;Isotope Labeling;Link;Lung;Lung Diseases;lung injury;Maps;Mediating;Methods;Mitochondria;Mitochondrial DNA;mitochondrial DNA mutation;mitochondrial genome;Modeling;Molecular;Mus;Mutation;Nature;novel;novel marker;Outcome;Oxidative Stress Induction;Parents;Pathway interactions;Pattern;Pattern recognition receptor;pharmacologic;Prevalence;prevent;Process;Reactive Oxygen Species;receptor;Recovery;repair function;repaired;Replication Error;Resolution;restoration;ribonuclease H1;Risk;risk minimization;Rodent;Severities;Signal Transduction;Somatic Mutation;specific biomarkers;Stimulus;Stress;Testing;Titrations;Transgenic Organisms;Work

PROJECT_TITLE: The mitochondrial genome in lung disease: a signaling hub linking the persistence and severity of inflammation to recovery

STUDY_SECTION: LIRR

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


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

ORG_CITY: SAN FRANCISCO

ORG_NAME: NORTHERN CALIFORNIA INSTITUTE/RES/EDU

PHR: NARRATIVE Deprescribing is an essential component of safe and effective health care for older adults. This proposal seeks to fund the next phase of the US Deprescribing Research Network, a national research network that aims to expand the quality, quantity, and translational impact of research on deprescribing for older adults. Through a series of connected cores and programs, the network will advance the science of deprescribing and elevate the research career development of investigators who are poised to lead the next generation of impactful scholarship in this field.

PI_NAMEs: BOYD, CYNTHIA MELINDA;STEINMAN, MICHAEL A. (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Address;Administrative Supplement;Adverse effects;adverse outcome;Alzheimer's disease related dementia;Area;Attention;Award;behavior change;career;career development;Caring;Clinical;clinical effect;clinical practice;Cognitive;Collaborations;Communities;community building;data harmonization;Dementia;Development;Education;Ensure;evidence base;Excision;frailty;functional decline;Functional impairment;Funding;Future;Generations;Geography;Goals;Grant;Growth;Health;Healthcare;high risk;high risk population;hypnotic;Medical Research;Mentorship;Methods;Mission;multiple chronic conditions;next generation;older adult;Paper;Persons;Pharmaceutical Preparations;Phase;Play;Population;Productivity;programs;R24;Research;research and development;Research Personnel;Research Project Grants;Research Support;Resources;Risk;Role;Scholarship;Science;sedative;Series;stakeholder perspectives;success;Testing;Thinking;tool;Translating;translational impact;translational potential;Work;working group

PROJECT_TITLE: The U.S. Deprescribing Research Network

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-2 (J1)]


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Cancer;Lung;Lung Cancer;Sleep Research

ORG_CITY: ROCHESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Project Narrative The cells of all mammals have daily internal cycles that are known as circadian rhythms, and many cancers, including lung cancers, have disrupted or absent circadian rhythms, but the reasons for this and its importance for tumor growth are not well understood. Lung cancers may shut down their circadian rhythms to grow more rapidly and resist therapy, and this proposal aims to study the role of the common oncogene MYC in blocking lung cancer cells from having a normal circadian rhythm, which may cause normal lung cells to turn into cancer cells and lose their ability to stop growing when exposed to steroids, either those naturally produced from the body or those used in treatment. We will determine how restoring circadian rhythmicity prevents lung cells from becoming cancer cells, and whether restoring rhythmicity makes lung cancer cells stop growing when treated with steroids as a therapy.

PI_NAMEs: ALTMAN, BRIAN JAMES (contact)

PROGRAM_OFFICER_NAME: LUO, RUIBAI

PROJECT_TERMS: Acceleration;Aggressive behavior;Alveolar;Alveolar Cell;alveolar epithelium;Architecture;ARNTL gene;Automobile Driving;Binding;Biological Assay;Biological Process;cancer biomarkers;cancer cell;Cell Cycle;Cell Cycle Regulation;Cell model;cell transformation;Cells;Chromatin;circadian;Circadian Dysregulation;Circadian gene expression;circadian pacemaker;Circadian Rhythms;Circulation;Clinical;Clinical Research;Complex;Data;Development;disabled;Disease;DNA;Down-Regulation;Epithelial Cells;Epithelium;experimental study;Exposure to;Family;Genetic Transcription;Glucocorticoid Receptor;Glucocorticoids;Growth;Hormones;Hour;Human;In Vitro;in vivo;in vivo Model;Link;Lung;Lung Adenocarcinoma;lung cancer cell;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Mammals;Mediating;Molecular;molecular clock;molecular subtypes;mouse model;Mus;MYC gene;Non-Small-Cell Lung Carcinoma;Oncoproteins;Organoids;overexpression;Patients;Periodicity;Peripheral;pharmacologic;pre-clinical;preclinical study;prevent;Process;Prognosis;Proliferating;promoter;Proteins;Repression;Resistance;resistance mechanism;response;restoration;restraint;Role;Sampling;Signal Transduction;Steroids;Testing;Time;transcription factor;tumor;tumor growth;tumor progression;tumorigenesis;Up-Regulation

PROJECT_TITLE: Disruption of the circadian clock in lung cancer

STUDY_SECTION: GRIC

STUDY_SECTION_NAME: Gene Regulation in Cancer Study Section[GRIC]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Prevention;Social Determinants of Health

ORG_CITY: PHILADELPHIA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Unhealthy diets are a significant contributor to major chronic diseases including heart disease and stroke, type 2 diabetes, and certain cancers. To advance our understanding of the policies needed to support healthy diets, our overall objective is to examine the degree to which a suite of healthy food policies influence online grocery store and restaurant purchases and dietary intake.

PI_NAMEs: ROBERTO, CHRISTINA ANN (contact);RUMMO, PASQUALE

PROGRAM_OFFICER_NAME: EVANS, MARY

PROJECT_TERMS: Accounting;Address;Adult;Agreement;Area;Behavior;Beverages;Chronic Disease;Cities;Data;design;dietary;Dietary intake;Disease;ethnic minority population;Evaluation;experimental study;Food;Food Industry;Food Labeling;food marketing;Food Packaging;Food Policy;Goals;good diet;Health;Health Food;health organization;Health Policy;Heart Diseases;High Prevalence;Household;improved;Industry;innovation;Intake;interest;Intervention;Interview;Location;Low income;Low Income Population;Malignant Neoplasms;Marketing;Methods;Non-Insulin-Dependent Diabetes Mellitus;nutrition;Nutrition Labeling;Obesity;Participant;Philadelphia;Policies;Policy Analysis;Population;prevent;Process;Public Health;Questionnaires;racial minority population;Randomized;recruit;Regulation;Research;Restaurants;Sales;Security;Stroke;sugar;Surveys;sweetened beverage;System;Taxes;Testing;Unhealthy Diet;United States National Institutes of Health;warning label;Work

PROJECT_TITLE: A longitudinal, randomized-controlled experiment of healthy food policies in online retail settings

STUDY_SECTION: LHB

STUDY_SECTION_NAME: Lifestyle and Health Behaviors Study Section[LHB]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

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

ORG_CITY: NORTH DARTMOUTH

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS DARTMOUTH

ORG_STATE: MA

PHR: Project Narrative This project aims to request funding to purchase a JASCO CD spectropolarimeter with adequate accessories to investigate the structural information of biological molecules. This instrument, currently unavailable to UMass Dartmouth, will promote the University's biomedical research and education capabilities. Broad access to this spectropolarimeter is expected with users from UMass Dartmouth, local academic institutes, and industry partners.

PI_NAMEs: CHANG, WEI-SHUN  (contact)

PROGRAM_OFFICER_NAME: BECKETT, DOROTHY

PROJECT_TERMS: Biochemistry;Biological;Biology;Biomedical Engineering;Biomedical Research;Cell Physiology;Chemistry;chiral molecule;Circular Dichroism;Collaborations;community college;Development;Education;Faculty;Fees;Funding;Goals;Grant;human disease;industry partner;instrument;Massachusetts;Measurement;member;Methods;nanoparticle;Play;programs;Research;Research Support;Role;Sampling;solid state;Structure;System;Temperature;Therapeutic;Titrations;tool;undergraduate student;United States National Institutes of Health;Universities

PROJECT_TITLE: CD spectropolarimeter

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDB-L (30)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dementia;Dietary Supplements;Microbiome;Natural Products;Neurodegenerative;Neurosciences;Nutrition;Prevention

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: RELEVANCE TO PUBLIC HEALTH This study will provide new information about how regular dietary polyphenol intake in the elderly population at risk of Alzheimer's disease (AD) will help maintain cognitive function and brain health. Specifically, it tests the hypothesis that polyphenol intake beneficially alters the brain-gut-microbiome system and healthier cognitive function. A better understanding of how polyphenols contribute to alterations in the brain and gut microbial metabolites in older adults with enhanced AD risk could lead to novel therapeutic strategies tailored to support healthy cognitive aging and reduce risk of disease.

PI_NAMEs: CHURCH, ARPANA  (contact);MAYER, EMERAN A

PROGRAM_OFFICER_NAME: MCLINDEN, KRISTINA

PROJECT_TERMS: Address;Affect;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease risk;Alzheimer’s disease biomarker;Anatomy;Animal Model;Atrophic;Autopsy;Axon;Behavior;Behavioral;Berry;bile acid metabolism;Bile Acids;Bioinformatics;Brain;brain health;Brain imaging;Brain region;Brain scan;brain volume;C-reactive protein;Cholic Acids;Cocoa Powder;Cognitive;Cognitive aging;cognitive function;Coupled;Data;data integration;dehydroxylation;Dementia;Deoxycholic Acid;Development;dietary;Dietary intake;Dietary Polyphenol;Disease Marker;disorder risk;dorsal raphe nucleus;Double-Blind Method;double-blind placebo controlled trial;effective therapy;Elderly;executive function;fecal transplantation;Fiber;flavan-3-ol;Flavonoids;flexibility;Food;Funding;Glial Fibrillary Acidic Protein;gut microbiome;gut microbiota;HDAC1 gene;Health;Health Care Costs;healthcare burden;Hippocampus;Human;Impaired cognition;improved;Inflammatory;inflammatory marker;Intake;Interleukin-1 beta;Interleukin-6;Interleukins;Intervention;Ireland;Light;locus ceruleus structure;Machine Learning;Measures;Mediating;Mediterranean Diet;Metabolic;metabolomics;microbial;microbiome;microbiota;microbiota metabolites;Molecular;mouse model;multimodality;Mus;myelination;Nerve Degeneration;neurofilament;Neuroglia;neuron loss;neuroprotection;Northern Ireland;novel;novel therapeutic intervention;older adult;Participant;Pathway interactions;Physiology;placebo controlled study;Placebos;Plasma;Play;polyphenol;Pontine structure;Population;Populations at Risk;preservation;Prevalence;prevent;programs;protective effect;Proteins;Public Health;Purines;Randomized;reconstitution;research and development;Risk;Risk Reduction;Role;Sampling;Serum;Short-Term Memory;Signal Transduction;Structure;Supplementation;Synaptic Transmission;System;tau Proteins;Tea;Techniques;Testing;TNF gene;Tocopherols;transcriptomics;translational approach;transplant model;Tryptophan;Tyrosine;United States;United States National Institutes of Health;Validation;White Matter Hyperintensity

PROJECT_TITLE: MAEVE: Microbiota mediated flavonoid metabolites for cognitive health

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Brain Disorders;Cancer;Childhood Leukemia;Digestive Diseases;Down Syndrome;Genetics;Hematology;Human Fetal Tissue;Intellectual and Developmental Disabilities (IDD);Liver Disease;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PHR: PROJECT NARRATIVE  Children with Down syndrome have a significantly increased risk of developing preleukemia during early childhood compared to children without Down syndrome. Our proposal aims to determine the molecular mechanisms that underlie the predisposition of trisomy 21 versus disomic hematopoietic stem cells towards initiating the preleukemic condition transient abnormal myelopoiesis. We are employing a combination of multi- omic analyses of human primary trisomy 21 fetal liver samples and subsequent functional interrogation using CRISPR/Cas9-mediated genome editing to uncover fundamental mechanisms and therapeutic targets of preleukemia in Down syndrome.

PI_NAMEs: WAGENBLAST, ELVIN  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute Myelocytic Leukemia;biological adaptation to stress;Blood;Bone Marrow;Candidate Disease Gene;CD34 gene;Cell Cycle Deregulation;Cell surface;Cell Transplantation;Cells;Cellular Structures;Child;Childhood;Chromosome 21;Chromosome abnormality;Chromosome Mapping;Clinic;Coculture Techniques;CRISPR/Cas technology;Development;Diagnosis;differential expression;Disease;Down's Syndrome;early childhood;Endothelial Cells;Erythroid;fetal;Fetal Development;Fetal Liver;fetal stem cell;Fibrosis;Frequencies;GATA1 gene;Gene Expression;Gene Mutation;genetic manipulation;Genetic Transcription;genome editing;Goals;Hematopoiesis;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Hepatocyte;high risk;Human;Immune;Immunodeficient Mouse;in utero;in vivo Model;Infant;Inflammation;inflammatory marker;Intrinsic factor;Knock-out;Lead;leukemia;Life;Ligands;Link;Live Birth;Liver;Liver Failure;Liver Fibrosis;Malignant Neoplasms;Maps;Mediating;Megakaryoblast;Microsatellite Repeats;Modeling;Molecular;multiple omics;Mutation;Myeloid Leukemia;Myelopoiesis;Neonatal;neonate;Newborn Infant;Pathway interactions;Patients;pharmacologic;Play;Predisposition;Preleukemia;prenatal;Process;progenitor;programs;Proliferating;Proteins;receptor;Research;Resolution;Risk;Role;Sampling;single-cell RNA sequencing;Site;Somatic Mutation;stem;stem cell migration;stem cells;stromal progenitor;System;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;transcription factor;transcriptomics;Translations;Twin Multiple Birth;Vision

PROJECT_TITLE: Intrinsic and Extrinsic Factors Contributing to Trisomy 21 Preleukemia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IVBH-B (57)]


NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Pediatric

PHR: PROJECT NARRATIVE Our previous study of nondiabetic, single autoantibody-positive (against glutamic acid decarboxylase, GADA+) donors revealed early dysfunction of glucagon-secreting α-cells which precedes the loss of insulin-secreting β- cell mass and function during the development of T1D. The proposed study will investigate whether this α-cell dysfunction is causally related to altered cAMP signaling and/or dysregulated bioenergetics in α-cells. This study will elucidate mechanisms underlying the specific defects in α-cell function during the progression of T1D.

PI_NAMEs: DOLIBA, NICOLAI  (contact);STOFFERS, DORIS A

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Affect;Alpha Cell;analog;arm;Autoantibodies;Beta Cell;Bioenergetics;Biological Assay;Biological Markers;Biosensor;Cell Aggregation;Cell Membrane Permeability;Cell Physiology;Cells;Clinical;Complex;Concentration Camps;Custom;Cyclic AMP;Cyclic AMP-Dependent Protein Kinases;Data;Defect;Development;Diabetes Mellitus;Disease;Down-Regulation;Electrophysiology (science);Evaluation;Exocytosis;experimental study;Functional disorder;Future;Genes;Genetic;Genetic Risk;Glucagon;Glucokinase;Glucose;glucose metabolism;Glutamate Decarboxylase;Glycolysis;Human;Hyperglycemia;Immune response;Impairment;Individual;insulin secretion;Insulin-Dependent Diabetes Mellitus;Intervention;Ion Channel;islet;Islet Cell;islet cell antibody;Islets of Langerhans;lens;Longitudinal Studies;Measurement;Measures;Membrane Potentials;Mitochondria;Modification;multidisciplinary;new therapeutic target;non-diabetic;Outcomes Research;Oxidative Phosphorylation;Pathogenesis;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Phenotype;PKA inhibitor;Positioning Attribute;prevent;Property;protein kinase inhibitor;ratiometric;Role;Signal Transduction;Spirometry;Symptoms;Testing;transcriptomics;Viral

PROJECT_TITLE: Role of Alpha Cells in Pathogenesis of Type 1 Diabetes

STUDY_SECTION: CSME

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


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Aging;Bioengineering;Cardiovascular;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Contraception/Reproduction;Maternal Health;Nanotechnology;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: GAINESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative The proposed research is relevant to public health because the development of placental therapies would lead to a treatment for Placental Insufficiency, Fetal Growth Restriction, Preterm birth and a reduced risk of developing adult diseases such as diabetes and cardiovascular disease. Furthermore, this study will elucidate mechanisms of Developmental Origins of Health and Disease and identify if treating the placenta will alleviate sequelae through the lifespan. Thus, the proposed research is relevant to the part of the NIH’s mission that pertains to fostering innovative research strategies and their applications as a basis for ultimately protecting and improving health as well as Themes 1, 3, 4 and 5 of the current NICHD strategic plan.

PI_NAMEs: JONES, HELEN N (contact)

PROGRAM_OFFICER_NAME: REN, ZHAOXIA

PROJECT_TERMS: Abnormal placentation;Accounting;Admission activity;Adult;Animal Model;Area;Award;biological adaptation to stress;Blood - brain barrier anatomy;Blood Vessels;Brain;cancer therapy;cardiogenesis;Cardiovascular Diseases;Cardiovascular system;Cavia;Cells;Cessation of life;Clinical Research;Complex;copolymer;Data;Development;Diabetes Mellitus;Diagnosis;Disease;effective therapy;Endocrinology;Environment;Etiology;Face;Failure to Thrive;feeding;fetal;fetal diagnosis;Fetal Growth;Fetal Growth Retardation;fetal programming;Fetal Reduction;Fetus;fetus nutrition;Fostering;Functional disorder;Gene Expression;gene therapy;Genes;genetic manipulation;Genetic Transcription;Goals;Growth;Growth Factor Gene;Health;healthy pregnancy;Heart;Human;Hydrocortisone;Image;Immune response;impaired brain development;improved;in utero;In Vitro;in vivo;Individual;infant morbidity;infant morbidity/mortality;Inflammation;Inflammatory;innovation;insight;Insulin-Like Growth Factor I;interest;Intervention;Knowledge;late life;Late pregnancy;Life;life span;Link;maternal nutrient restriction;Mediating;Metabolic;Metabolic Diseases;Mission;Modeling;Molecular;Mus;nanoparticle;nanopolymer;National Institute of Child Health and Human Development;neonatal period;neuroinflammation;Neurologic;Newborn Infant;novel;Nutrient;offspring;Operative Surgical Procedures;Organ;organ growth;Oxidative Stress;Pathway interactions;Perfusion;Physiological;Physiological Adaptation;Placenta;Placenta Diseases;Placental Insufficiency;placental trophoblasts;Placentation;Plasmids;Pregnancy;Pregnancy Complications;pregnancy prevention;pregnant;Premature Birth;prenatal therapy;prevent;promoter;Public Health;Regulation;Regulatory Pathway;Research;Respiratory Disease;response;restoration;Risk;Risk Reduction;Safety;Signal Pathway;Signal Transduction;Sterility;Strategic Planning;Stress;Stretching;Stroke;Structure;Syncytiotrophoblast;Systems Biology;targeted treatment;Testing;Therapeutic;therapeutic nanoparticles;Time;Tissues;translational impact;trophoblast;United States National Institutes of Health;uptake;Vascularization

PROJECT_TITLE: Placental-specific therapy for fetal growth restriction

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Cardiovascular;Heart Disease;Muscular Dystrophy;Nutrition;Obesity;Orphan Drug;Rare Diseases

PHR: Project Narrative This project advances our basic research technology, used to understand the regulation of intracellular calcium in the heart, toward the high-throughput application to early-phase drug discovery. This work is driven by the motivation to design more effective therapeutic approaches for heart disease, and identify compounds that may be used as chemical probes to further understand regulation of intracellular calcium. More generally, this work will also provide insight into other Public Health challenges involving faulty calcium regulation, such as diabetes, obesity, Alzheimer’s, Parkinson’s, and muscular dystrophy. 1

PI_NAMEs: REBBECK, ROBYN T;THOMAS, DAVID D (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: absorption;Acceleration;Adult;Affinity;Alzheimer's Disease;analog;Anti-Arrhythmia Agents;Arrhythmia;ATP phosphohydrolase;Automobile Driving;Basic Science;Binding;Biochemical;Biological Assay;Biophysics;Biosensor;Calcium;Cardiac;Cardiac Myocytes;Cardiology;Cells;Characteristics;Chemicals;Clinical;Clinical Data;Critical Pathways;design;Development;Diabetes Mellitus;Disease;Dose;drug development;drug discovery;Drug Kinetics;Drug Targeting;Drug Transport;dwarf open reading frame;Ensure;Enzymes;FDA approved;Fluorescence;Fluorescence Resonance Energy Transfer;Fluorescence Spectroscopy;Future;genetic regulatory protein;Goals;Heart;Heart Diseases;Heart failure;high throughput screening;Human;Implementation readiness;in vivo;Industrialization;industry partner;innovation;insight;Lead;Leadership;Lipids;Malignant Neoplasms;Measures;Membrane;Metabolism;Methods;Molecular;Motivation;Muscle;Muscle Cells;Muscular Dystrophies;Myocardium;novel;Obesity;Outcome;Parkinson Disease;Peptides;Pharmaceutical Chemistry;Phase;phospholamban;Process;programs;Property;Protein Dynamics;Protein Isoforms;protein protein interaction;Proteins;Proteolysis;Public Health;Pump;Reader;Regulation;Relaxation;Reproducibility;Research;Resolution;Running;sarcolipin;sarcopenia;Sarcoplasmic Reticulum;Scanning;screening;SERCA2a;skeletal;Skeletal Muscle;small molecule;small molecule libraries;Structure;Structure-Activity Relationship;success;System;Techniques;Technology;Testing;Therapeutic;therapeutic target;therapeutically effective;Tissues;tool;Toxic effect;Translating;Translations;Tryptophan;Validation;Ventricular;Work

PROJECT_TITLE: Protein structural biophysics driving drug discovery for cardiac calcium transport regulation, producing translational advances and mechanistic insights

STUDY_SECTION: CBP

STUDY_SECTION_NAME: Chemical Biology and Probes Study Section[CBP]


ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The goals of this project are to define how mitochondria regulate telomere length reprogramming during mammalian embryogenesis using complementary animal models that provide insight into human embryo development. Moreover, therapies will be developed that mitigate defects in the telomere elongation process to ensure normal fetal and postnatal development, as well as healthy aging.

PI_NAMEs: HENNEBOLD, JON D (contact);ROBKER, REBECCA LOUISE

PROGRAM_OFFICER_NAME: RAVINDRANATH, NEELAKANTA

PROJECT_TERMS: 10 year old;Adult Children;Age related comorbidities;age-related disease;Aging;Animal Model;Animals;Automobile Driving;Bioenergetics;Biological Assay;Biology;Birth;blastocyst;Body Weight decreased;Cardiovascular Diseases;Cell Aging;Cell division;Child;Chromosomes;Clinical;clinically relevant;Communication;Conceptions;Consumption;Data;Defect;Development;Developmental Process;Diet;disorder risk;DNA;DNA Damage;DNA Sequence;Embryo;Embryonic Development;Endowment;Ensure;Event;Exhibits;Fat-Restricted Diet;Female;Fertilization;fetal;Functional disorder;Future;Gene Expression;Generations;Genetic Transcription;Genome;Genome Stability;Genomics;Goals;Health;healthy aging;Human;human embryonic development;human model;human old age (65+);Impairment;improved;Individual;Inner Cell Mass;insight;Intervention;Lead;Length;Leukocytes;Life;life span;Link;Longevity;Macaca mulatta;maternal obesity;Maternal Physiology;Measures;Membrane Potentials;Metabolic syndrome;Micromanipulation;Mitochondria;mitochondrial dysfunction;mitochondrial membrane;Modeling;Modification;Molecular;mortality;Morula;Mus;Natural regeneration;nonhuman primate;Nuclear;Obese Mice;obese mothers;Obesity;obesity in children;obesogenic;offspring;Oocytes;Outcome;Ovarian Stimulations;oxidative DNA damage;Oxidative Stress;Pathology;Physiological;Play;postnatal development;pre-clinical;Pre-implantation Embryo Development;Pregnancy;preimplantation;Prevalence;Primates;Process;Production;programs;Reactive Oxygen Species;Regulation;Reporting;Risk;Role;Rotenone;Safety;Somatic Cell;Source;stem cells;Telomerase;telomere;Telomere Shortening;Testing;Therapeutic;therapeutic target;Tissues;tool;transcriptional reprogramming;Voltage-Dependent Anion Channel;western diet;Woman;Work;zygote

PROJECT_TITLE: Oocyte mitochondrial activity regulates embryo telomere reprogramming

STUDY_SECTION: CMIR

STUDY_SECTION_NAME: Cellular, Molecular and Integrative Reproduction Study Section[CMIR]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Heart Disease;Heart Disease - Coronary Heart Disease;Nutrition;Prevention;Women's Health Research

ORG_CITY: NEW ORLEANS

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Narrative Circulating proteomic profiles are strongly influenced by diet and may act as important molecular transducers of the diet’s effects on coronary heart disease (CHD). Using exceptional resource from six independent and well-characterized prospective cohorts, the study proposes to perform proteome-wide study on the dynamic interrelations between diet (quality and circadian/temporal eating patterns), circulating proteome and its changes over 10 years, and CHD risk. We will also investigate the mediation effects of non-protein vascular risk factors, and multi-omics proteome-metabolome associations with CHD. Our findings are expected to provide novel insight into the mechanistic pathways, and advance the development of new preventive and therapeutic strategies.

PI_NAMEs: MANSON, JOANN ELISABETH;QI, LU  (contact)

PROGRAM_OFFICER_NAME: PRICE, CANDICE

PROJECT_TERMS: Advanced Development;Affect;Beverages;biobank;Biological Markers;Blood;Cardiometabolic Disease;cardiometabolism;career;circadian;cohort;Coronary Artery Risk Development in Young Adults Study;Coronary heart disease;cost efficient;Data;design;Development;Diet;Diet Habits;Diet Records;dietary;Dietary Factors;Dietary intake;Dietary Practices;Disease Progression;disorder control;doubly-labeled water;Eating;Food;Frequencies;Funding;Genetic Predisposition to Disease;Glycosylated hemoglobin A;Goals;heart disease risk;Human;Incidence;Inflammation;insight;Jackson Heart Study;Joints;Knowledge;Life Style;lifestyle factors;Link;Lipids;Machine Learning;Measures;Mediating;Mediation;metabolome;Methods;Molecular;multiple omics;novel;Nurses' Health Study;Nutrient;Nutrition Assessment;Participant;Pathway interactions;Pattern;Plasma;Preventive;Prospective cohort;Prospective, cohort study;Proteome;Proteomics;Publications;Research Personnel;Resources;Risk;Risk Factors;Role;Sampling;secondary analysis;Testing;Therapeutic;Training;Transducers;urinary;validation studies;vascular risk factor;Woman;Work

PROJECT_TITLE: RISK FACTORS FOR CVD IN WOMEN

STUDY_SECTION: CRD

STUDY_SECTION_NAME: Cardiovascular and Respiratory Diseases Study Section[CRD]


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Genetics;Hepatitis;Liver Disease;Nutrition

PHR: PROJECT NARRATIVE Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, can lead to cirrhosis, liver cancer, and death. The underlying mechanisms that drive this process are multifactorial and remain poorly understood. The proposed research aims to characterize the role of a novel LXR-regulated gene in liver lipid homeostasis and NAFLD pathogenesis, potentially revealing novel pathways to be therapeutically targeted in metabolic liver disease.

PI_NAMEs: NGUYEN, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Adverse effects;Advisory Committees;Affect;Agonist;Award;Bile Acid Biosynthesis Pathway;Biliary;Binding;career;career development;cell growth regulation;Cells;Cessation of life;Cholesterol;Cholesterol Homeostasis;Chronic;chronic liver disease;Cirrhosis;Clinical Sciences;Core Facility;CRISPR/Cas technology;Defect;Development;Diet;dietary;Dietary Fats;Doctor of Medicine;Doctor of Philosophy;Drug Metabolic Detoxication;Equilibrium;Excretory function;Fellowship;Fibrosis;Gastroenterologist;Gastroenterology;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;gene function;Genes;Goals;Hepatic;Hepatocyte;Homeostasis;Human;in vivo;Inflammation;inflammatory marker;Institution;Internal Medicine;International;Knock-out;Knockout Mice;Lecithin;lipid biosynthesis;lipid metabolism;Lipids;Lipoproteins;Liver;liver biopsy;Liver diseases;liver function;liver metabolism;Liver X Receptor;Malignant neoplasm of liver;Mediating;medical schools;Mentors;Mentorship;Metabolic;Metabolism;Methyltransferase;Methyltransferase Gene;Modeling;Molecular;Mus;Mutate;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;novel therapeutic intervention;Nuclear Hormone Receptors;Nutritional;Pathogenesis;Pathway interactions;Patients;Phospholipids;Physicians;Physiological;Physiology;Play;Postdoctoral Fellow;prevent;Process;programs;promoter;Receptor Activation;Research;Research Personnel;Research Proposals;Residencies;Resources;Response Elements;Role;Scientist;small molecule;Steatohepatitis;Stimulus;Substrate Specificity;Testing;Therapeutic;therapeutic target;Tissues;Training;transcription factor;Transcriptional Activation;Transcriptional Regulation;Translational Research;uptake;Work;Xenobiotics

PROJECT_TITLE: Role of a Novel Methyltransferase in Liver Lipid Metabolism

STUDY_SECTION: DDK

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Cancer;Congenital Structural Anomalies;Pediatric;Rare Diseases;Wound Healing and Care

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: Project Narrative Our recently published work has identified a novel role in cellular secretion for type VII collagen, the largest of human collagen molecules, and our unpublished data have identified anti-viral compounds as potential drugs that can normalize disruption to secretion after loss of functional type VII collagen. Absent or non-functional type VII collagen leads to the devastating inherited disease recessive dystrophic epidermolysis bullosa characterized by skin and mucosa fragility, chronic wounds, progressive fibrosis and cancer. This project seeks to understand the secretory defects resulting from loss of functional type VII collagen and determine the mechanism of action for anti-viral drugs which we show can extend the lifespan of a murine model of recessive dystrophic epidermolysis bullosa.

PI_NAMEs: SOUTH, ANDREW  (contact)

PROGRAM_OFFICER_NAME: KOCH, PETER

PROJECT_TERMS: Address;Adhesions;Animals;anterograde transport;Anti-viral Agents;Binding;Bulla;Cause of Death;Cell secretion;Cells;Cellular Stress;chronic wound;Cicatrix;Clinic;Clinical Trials;clinically relevant;COL7A1;Collagen;Collagen Type VII;Data;Defect;Deposition;Dermal;Destinations;Development;Disease;drug candidate;Endoplasmic Reticulum;endoplasmic reticulum stress;Endosomes;Epidermolysis Bullosa;Epidermolysis Bullosa Dystrophica;extend lifespan;Extracellular Matrix;Extracellular Matrix Proteins;Fibroblasts;Fibrosis;functional loss;Funding;Future;Genes;genetic manipulation;Golgi Apparatus;Hereditary Disease;Human;improved;In Vitro;in vitro Assay;in vivo;Lead;Life;Ligands;Link;live cell imaging;loss of function;Malignant Neoplasms;Mediating;Membrane Protein Traffic;Microscopy;Molecular;mouse model;Mucous Membrane;Mutation;non-healing wounds;novel;novel therapeutic intervention;particle;Pathogenesis;Pathology;Pathway interactions;Patients;Pharmaceutical Preparations;pre-clinical;pre-clinical assessment;preclinical efficacy;prevent;Process;Production;Protein Isoforms;Protein Secretion;Proteins;Publishing;Recycling;Role;scaffold;Secretory Vesicles;Series;shift work;Signal Transduction;Skin;Skin Cancer;spatial relationship;Squamous cell carcinoma;System;Testing;Thrombospondin 1;Time;Tissues;Transforming Growth Factor beta;Translating;Trauma;Vesicle;Viral;Western Blotting;Work;wound;wound healing

PROJECT_TITLE: The role of collagen VII in extracellular matrix protein secretion

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


ORG_CITY: SAN MARCOS

ORG_NAME: TEXAS STATE UNIVERSITY

ORG_STATE: TX

PHR: Myriad proteins — from those that process methane in our gut to those used by fungal pathogens to sequester nutrients from their hosts — function by exploiting metal centers with unpaired electrons. These centers are best studied using electron paramagnetic resonance spectroscopy, wherein microwave radiation perturbs these electrons and teaches us about the nature of the metal. Texas State University wishes to acquire an electron paramagnetic resonance spectrometer to support research on biological and synthetic samples, as well as offer valuable hands-on experiences in students’ coursework.

PI_NAMEs: SCHILTER, DAVID  (contact)

PROJECT_TERMS: Active Sites;base;Biochemistry;Biological;Biology;Biomedical Research;Biotechnology;Books;Carrier Proteins;Chemistry;college;Complex;Copper;cost;Data Collection;Discipline;Education;Educational process of instructing;Electron Spin Resonance Spectroscopy;Electrons;Energy Metabolism;Engineering;experience;Geometry;Hispanic-serving Institution;instrument;materials science;Measurement;metal complex;metalloenzyme;Methane;mutant;Nature;NMR Spectroscopy;operation;Operations Research;Oxidation-Reduction;Oxygen;pathogenic fungus;programs;Protein Isoforms;Research;Resolution;Sampling;Science;Scientist;Students;System;Techniques;Temperature;Texas;Training;Transition Elements;undergraduate student;Universities;uptake

PROJECT_TITLE: Continuous-Wave X-Band Electron Paramagnetic Resonance Spectrometer


NIH_SPENDING_CATS: Lung

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

PHR: Our preliminary data suggest that DHRS9 is a robust, broadly specific oxylipin dehydrogenase, which plays an important role in the regulation of inflammation in lungs. This project seeks to characterize the specificity of DHRS9 toward the major classes of biologically active oxylipins, to elucidate the molecular basis of the substrate specificity of DHRS9 for oxylipin substrates, and to establish the nature of physiological derangements associated with deficiency of DHRS9. The results of these studies will lay the foundation for the development of new approaches targeting lung inflammation.

PI_NAMEs: KEDISHVILI, NATALIA Y (contact);POPOV, KIRILL M

PROGRAM_OFFICER_NAME: ESPINOZA GRANDON, INGRID CECILIA

PROJECT_TERMS: Acids;Acute Lung Injury;Affect;Agreement;Anabolism;Anti-Inflammatory Agents;Arachidonic Acids;Binding;Biochemical Reaction;Biological;Blood coagulation;Catabolism;Cells;Characteristics;chemokine;Complex;cytokine;Data;design;Development;dietary;Disease;Disease Progression;Docosahexaenoic Acids;docosapentaenoic acid;Dryness;Dyes;Edema;Eicosanoids;Eicosapentaenoic Acid;Environment;Enzymatic Biochemistry;Enzyme-Linked Immunosorbent Assay;Enzymes;Equilibrium;Evans blue stain;Exhibits;experimental study;Extravasation;Family;Flow Cytometry;Foundations;Gastric Acid;Goals;Human;Hydroxyeicosatetraenoic Acids;hydroxyl group;Hydroxylation;Immune;Immune response;Immunoassay;Immunology;Inflammation;Inflammation Mediators;Inflammatory;influenzavirus;Injury;Kinetics;Knowledge;Leukotriene B4;Link;Linoleic Acids;lipid mediator;lipidomics;Lipopolysaccharides;lipoxin A4;Lipoxins;Lung;lung injury;Mass Fragmentography;Mass Spectrum Analysis;Mediating;Mediator;member;Metabolic;Metabolic Pathway;Metabolism;Microsomes;Modeling;Molecular;Mus;Nature;Neutrophil Infiltration;novel;novel strategies;Organ;oxidation;Oxidoreductase;Pain;Pathology;Pathway interactions;Permeability;pharmacologic;Physiological;Play;Polyunsaturated Fatty Acids;Population;Positioning Attribute;Predisposition;Production;Prostaglandins;Proteins;Publishing;Pulmonary Inflammation;Reaction;Regulation;Research;Resolution;response;Role;Scheme;Site-Directed Mutagenesis;Specificity;Stimulus;structural biology;Structure;Structure of parenchyma of lung;Substrate Specificity;Testing;Therapeutic;three dimensional structure;Tissues;Transgenic Model;Weight

PROJECT_TITLE: Role of DHRS9 in oxylipin metabolism


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Down Syndrome;Epilepsy;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Pediatric

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it will identify molecular regulators that underlie comorbidities in Down syndrome, which will offer insights into the development of therapeutic treatments that target these conditions. It will also provide molecular and cellular insights into other neurological disorders, such as intellectual disabilities, epilepsy, and ASD. Thus, the proposed research is relevant to NIH’s mission because it is expected to develop fundamental knowledge that will help to reduce the burdens of disease and disability.

PI_NAMEs: DIERSSEN, MARA ;VALERO GARCIA, MANUEL ;YE, BING  (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Affect;Alzheimer's Disease;autism spectrum disorder;burden of illness;cell type;Cells;Characteristics;Chromosome 21;cognitive ability;Cognitive deficits;cognitive function;cognitive performance;comorbidity;Development;disability;Disease;Down Syndrome Cell Adhesion Molecule;Down's Syndrome;effective therapy;Epilepsy;Epileptogenesis;Functional disorder;Gene Expression Profile;Genes;Genetic;granule cell;hippocampal pyramidal neuron;Hippocampus;Human;Human Chromosomes;Hyperactivity;Impairment;in vivo;Inhibitory Synapse;innovation;insight;Intellectual functioning disability;Interneurons;Knowledge;Laboratory Finding;Learning;Link;Memory;Memory impairment;Mission;Molecular;mouse model;mouse Ts65Dn;Mus;Neocortex;Nervous System Disorder;Neurologic;neuromechanism;Neurons;neurotransmission;novel;overexpression;Parvalbumins;Pharmaceutical Preparations;Play;Population;Positioning Attribute;Public Health;Research;Resolution;restraint;Risk;Role;Seizures;Synapses;Synaptic plasticity;Synaptic Transmission;synaptogenesis;System;Techniques;Temporal Lobe Epilepsy;Testing;therapeutic development;transcriptomics;Trisomy;United States National Institutes of Health;Variant

PROJECT_TITLE: Molecular regulators of GABAergic systems that underlie comorbidities in Down syndrome


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Neurosciences

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Deuterium metabolic imaging (DMI) is a novel MR-based method to image metabolism of deuterium-labeled substrates in healthy or diseased human brain, whereby the unique metabolic information has shown clinical potential in patients with aggressive brain tumors. Establishing clinical relevance of DMI requires studies on larger patient populations, during which standard, but time-consuming sequential acquisition of DMI and MRI can compromise patient compliance and system throughput. Here we pursue the technical development of time- efficient parallel acquisition of MRI and DMI to accelerate the practical use of DMI in a clinical MR environment.

PI_NAMEs: DE GRAAF, ROBIN A (contact)

PROGRAM_OFFICER_NAME: BARRY, ROBERT LEO II

PROJECT_TERMS: Acceleration;Address;Adopted;anatomic imaging;Anatomy;base;Blinded;Brain;Brain imaging;Brain Neoplasms;Cancer Detection;Cell Nucleus;Clinical;clinical implementation;Clinical Research;clinical research site;clinically relevant;Computer software;Consumption;contrast imaging;cost;Data;Dedications;design;Detection;Deuterium;deuteron;Development;Diffusion Magnetic Resonance Imaging;Elements;Environment;experience;Frequencies;Glucose;glucose metabolism;Goals;Head;healthy volunteer;Hour;Human;human disease;Image;imaging detection;imaging modality;Imaging Techniques;in vivo;in vivo evaluation;interest;intravenous administration;Label;Length;magnetic field;Magnetic Resonance Imaging;Maps;Metabolic;metabolic imaging;Metabolism;Methods;Modification;Morphologic artifacts;novel;Oral Administration;Patient Compliance;patient population;Patients;Philosophy;Positioning Attribute;Predisposition;Protocols documentation;Protons;radio frequency;Research;research clinical testing;Resolution;Scanning;Scheme;Shapes;Shoulder;Signal Transduction;software development;spectroscopic imaging;System;Techniques;technological innovation;Testing;Time;Translating;tumor;Validation;volunteer;Warburg Effect

PROJECT_TITLE: Time-efficient MRI and deuterium metabolic imaging (DMI) through parallel signal acquisition

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


NIH_SPENDING_CATS: Aging;Clinical Research;Dietary Supplements;Genetics;Hematology;Human Genome;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: PROJECT NARRATIVE Clonal hematopoiesis of indeterminate potential (CHIP) is strongly linked to aging and confers to an increased risk for blood cancers, non-hematological diseases, and all-cause mortality. ASXL1 is one of the commonly mutated genes in CHIP. In particular, the hotspot frameshift mutation at codon 646 (corresponding to codon G643 in mice-Asxl1tm) represents pathological CHIP mutation with high risk to drive myeloid diseases. Corroborating this observation in humans, we recently found that Asxl1tm/+ bone marrow cells and hematopoietic stem cells underwent significant expansion in old/aged recipients (20-24 months) but not in young recipients (2- 4 months old). In this R01 application, we propose to study the molecular and cellular mechanisms underlying mutant Asxl1-driven CH. The central goal of this proposal aims to provide fundamental insights into ASXL1 mutations-driven CH and serve the basis for future development of preventative and/or therapeutic strategies.

PI_NAMEs: ZHANG, JING  (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: aged;Aging;aging related;Apoptotic;Applications Grants;BCL2 gene;BCL2L1 gene;Biological Assay;Blood Cells;bone aging;Bone Marrow;Bone Marrow Cells;Bromodomains and extra-terminal domain inhibitor;C-terminal;Cell Surface Proteins;Cell Survival;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Cleavage Under Targets and Release Using Nuclease;Clonal Expansion;Codon Nucleotides;Coupled;Data;Development;Dietary Supplementation;Disease;DNMT3a;DNMT3a mutation;Endothelial Cells;Enhancers;Epigenetic Process;experimental study;Flow Cytometry;Frameshift Mutation;Frequencies;Future;Genes;Goals;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic Neoplasms;hematopoietic stem cell expansion;Hematopoietic stem cells;high risk;Histones;Human;Immune;In Vitro;in vivo;Inflammatory;inhibitor;insight;Interleukin-1 beta;Lead;Length;Link;mesenchymal stromal cell;Molecular;mortality;Mus;mutant;Mutate;Mutation;myeloid leukemia cell;Myeloproliferative disease;neutrophil;nicotinamide riboside supplementation;nicotinamide-beta-riboside;Non-Malignant;Nonsense Mutation;old mice;overexpression;Pathogenesis;Pathologic;Patients;PH Domain;Phenotype;Population;Preleukemia;prevent;Prevention;programs;Protein Truncation;Proteins;Resolution;response;Risk;RNA analysis;Sampling;senescence;senescent cell;Serum;single-cell RNA sequencing;systemic inflammatory response;Testing;Therapeutic;transcriptome sequencing;transcriptomics;Transplant Recipients;Transplantation;Validation

PROJECT_TITLE: Molecular and Cellular Mechanisms of Mutant ASXL1-driven Clonal Hematopoiesis

STUDY_SECTION: CMAD

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Pediatric;Pediatric Cancer;Prevention;Rare Diseases;Skin Cancer

ORG_CITY: BLOOMINGTON

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative While exposure to UV light between the ages of 15-20 is the most important etiological factor for skin cancer risk, adolescent and young adult (AYA) boys/men and girls/women and young gay and bisexual boys/men (GBBM) are more likely to engage in health-compromising behaviors like indoor and outdoor tanning without the use of skin protection. The goals of this project are to 1) characterize the social media landscape regarding skin cancer-related posts; and 2) develop and test messages for skin cancer prevention among at-risk adolescents and young adults that are clear, specific, consistent, and scientifically up to date. This project is relevant to public health because it will contribute to the skin cancer prevention knowledge base and to improved skin cancer- related communication/messaging on social media; it will provide a strong basis for the future development of improved and targeted prevention efforts via digital platforms frequently used and easily accessed by these young priority populations, effectively supporting The Surgeon General’s Call to Action to Prevent Skin Cancer and the National Cancer Institute’s mission to “advance scientific knowledge and help all people live longer, healthier lives”.

PI_NAMEs: WALSH-BUHI, ERIC RICHARD (contact)

PROGRAM_OFFICER_NAME: CHOU, WEN-YING

PROJECT_TERMS: 17 year old;20 year old;Adolescent and Young Adult;Adult;Age;aged;analytical method;Behavior;behavior change;Bisexual;Black race;boys;Cancer Prevention Intervention;cancer risk;Characteristics;checkup examination;Code;Communication;design;Development;Diffuse Pattern;Diffusion;digital platform;Education;Etiology;Evaluation;Exposure to;Facebook;Future;future implementation;Gays;girls;Goals;Health;health communication;Heterosexuals;Hispanic;Human;human centered design;improved;innovation;Instagram;Intervention;Knowledge;knowledge base;Libraries;machine learning method;Male Adolescents;Malignant Neoplasms;Measures;men;Methods;Misinformation;Mission;Modality;Modeling;multidisciplinary;multilevel analysis;National Cancer Institute;Not Hispanic or Latino;peer;Persons;Physicians;pilot test;Population;posters;predictive modeling;Prevention;Proliferating;Public Health;Publishing;Reporting;Research;Risk;Sampling;Scientific Advances and Accomplishments;Skin;Skin Cancer;skin cancer prevention;Skin Care;Skin tanning;social media;Social Network;social organization;Source;Subgroup;sun protection;sun safety;Sunburn;Sunscreening Agents;Surgeon;tanning booths;Testing;the sun;training data;Twitter;Ultraviolet Rays;Woman;Work

PROJECT_TITLE: Skin cancer on social media: Analyzing current communications, modeling diffusion potential, and developing innovative prevention-focused messages

STUDY_SECTION: HPC

STUDY_SECTION_NAME: Health Promotion in Communities Study Section[HPC]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_DEPT: NEUROSCIENCES

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: PROJECT NARRATIVE  The studies proposed in this application will enhance our understanding of phototransduction and vision in retinal rods and cones, in both human health and disease.

PI_NAMEs: YAU, KING-WAI  (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TITLE: Phototransduction and Signaling in Photoreceptors

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Nanotechnology

ORG_CITY: SAN JOSE

ORG_NAME: SAN JOSE STATE UNIVERSITY

PHR: Project Narrative We request the purchase of a circular dichroism spectrophotometer. This instrument is crucial in characterizing the structure and stability of molecules involved in human diseases, drug development and delivery, antibiotic resistance and biomaterials. This instrument will greatly increase the breadth, depth and efficiency of research at SJSU and surrounding institutions; as well as give students hands-on experience in a classroom setting to help enhance their career-related skills.

PI_NAMEs: WANG, NINGKUN  (contact)

PROJECT_TERMS: 20 year old;Academia;Area;Biochemical;Biochemistry;Biomedical Engineering;Biomedical Research;career;Circular Dichroism;circular magnetic dichroism;Complex;Detection;Education;Equipment;experience;experimental study;Fluorescence;Funding;Future;Goals;Grant;improved;Industry;Inorganic Chemistry;Institution;instrument;Journals;laboratory curriculum;Ligands;materials science;Metals;Modeling;Nanotechnology;Organic Chemistry;Peer Review;Peptides;Proteins;Publishing;Request for Applications;Research;Research Personnel;Research Support;Sampling;small molecule;Spectrophotometry;Structure;Students;Techniques;Temperature;Titrations;undergraduate research experience;United States National Institutes of Health;Universities

PROJECT_TITLE: Circular Dichroism Spectrophotometer


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza;Prevention

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: IgG antibodies are critical for protecting against respiratory viruses, yet a detailed understanding of how they mediate immunity in the lung is lacking. Experiments proposed here will define how distinct glycosylation patterns of IgG antibodies impact their functional properties against the respiratory pathogens SARS-CoV-2 and influenza viruses. These studies are designed to address several key gaps in knowledge around basic antibody biology, mechanisms of lung immunity, and the pathogenesis of SARS-CoV-2 and influenza virus infections with the goal of improving pandemic preparedness and treatments against these and potentially other important human respiratory viral pathogens.

PI_NAMEs: DIAMOND, MICHAEL S;WANG, TAIA  (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: 2019-nCoV;Acute Respiratory Distress Syndrome;Address;Affect;Affinity;Alveolar Macrophages;Anti-Inflammatory Agents;Antibodies;Antibody-mediated protection;Antigen Presentation;Antigen-Antibody Complex;autocrine;Binding;Biology;Bronchoalveolar Lavage Fluid;Cell Maturation;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Cellular Infiltration;chemokine;cytokine;Data;design;disorder risk;experimental study;Fc domain;Fc Receptor;Gases;Genetic Transcription;glycosylated IgG;glycosylation;Goals;Heterogeneity;Human;Immune;immune function;Immune response;Immunity;Immunization;Immunoglobulin G;improved;in vivo;in vivo Model;Infection;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;Influenza A virus;influenza infection;influenzavirus;interest;Knowledge;Lung;Lung Capacity;lung histology;Lung immune response;Mediating;Modeling;Modification;Molecular;Morbidity - disease rate;mortality;Mus;Netherlands;novel;Outcome;pandemic preparedness;paracrine;Pathogenesis;pathogenic virus;Pathway interactions;Pattern;Persons;Phagocytosis;Phenotype;PIK3CG gene;Polysaccharides;Post-Translational Protein Processing;prevent;Production;Property;protein expression;Pulmonary Inflammation;receptor;recruit;Regulation;respiratory;respiratory infection virus;respiratory pathogen;Respiratory Tract Infections;respiratory virus;response;Role;SARS-CoV-2 antibody;SARS-CoV-2 pathogenesis;Sentinel;severe COVID-19;Severity of illness;sialylation;Signal Pathway;Signal Transduction;Site;Symptoms;System;Testing;Time;tissue injury;Tissues;TNF gene;Transcriptional Regulation;Transgenic Mice;Tropism;Viral;Viral Respiratory Tract Infection;Virus;Virus Diseases;Work

PROJECT_TITLE: Regulation Of Lung Immunity By Antibody Glycosylation

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Bioengineering;Biotechnology;Genetics;Human Genome;Infectious Diseases

ORG_CITY: DALLAS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Imbalanced enzyme production inside a cell can lead to inefficient metabolism, altered cell growth, and disease in all organisms, yet the amount of each enzyme necessary for “normal” cell function is poorly characterized. The goals of this grant are to: (1) measure the constraints on intracellular enzyme abundance in E. coli, and (2) use these data to create models predicting how E. coli drug resistance and growth change in response to the abundance of different enzymes. This work has potential to reveal new antibiotic targets, define rules for engineering metabolic pathways, and will create a suite of tools for measuring and predicting enzyme abundance-growth rate relationships for use by the broader scientific community.

PI_NAMEs: REYNOLDS, KIMBERLY ANN (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Address;amino acid metabolism;Anabolism;Antibiotic Resistance;Antibiotics;Bar Codes;biological adaptation to stress;cell growth;Cell Physiology;Cells;Chromosome Mapping;Clinical;Collection;combinatorial;Communities;comparative;Copy Number Polymorphism;CRISPR interference;Data;Data Set;Dihydrofolate Reductase;Disease;Drug resistance;Engineering;Environment;Environmental Risk Factor;Enzymes;Escherichia coli;Escherichia coli drug resistance;experimental study;Folic Acid;Foundations;Funding;Gene Expression;gene expression variation;gene product;gene repression;Genes;Genetic;Genetic Epistasis;Genetic Variation;genome editing;genome-wide;Genomics;Goals;Grant;Growth;Guide RNA;interest;knock-down;Knowledge;Laboratories;Left;machine learning model;Maps;Measurement;Measures;Mediating;Metabolic;Metabolic Diseases;metabolic engineering;Metabolic Pathway;Metabolism;Methods;Modeling;Molecular;Monitor;Mutation;new therapeutic target;Noise;Normal Cell;Nucleotide Biosynthesis;Nutrient;Operon;Organism;Pathway interactions;Pharmacogenomics;Phenotype;Plasmids;Play;pleiotropism;predictive modeling;Production;Proteins;Purine Nucleotides;Repression;Resources;response;Reverse Transcriptase Polymerase Chain Reaction;ribosome profiling;RNA;Role;Sampling;Shapes;Source;stoichiometry;stressor;Structure;Synteny;System;Testing;Thymidine;Time;Titrations;tool;Training;training data;transcriptome sequencing;Trimethoprim;Trimethoprim Resistance;Variant;Work

PROJECT_TITLE: Mapping genetic variation in enzyme velocity to growth rate phenotype

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


NIH_SPENDING_CATS: Digestive Diseases;Liver Disease;Neurodegenerative;Nutrition;Prevention;Rare Diseases

ORG_CITY: BALTIMORE

PHR: PROJECT NARATIVE Dysregulation of nutrient absorption is detrimental to human health and causes a broad spectrum of disorders. This project will determine absorption of copper and fat in small intestine are co-regulated and how this process is altered in disease. The results will offer new approaches to regulate fat absorption in healthy intestine and to fine-tune treatments for Wilson disease.

PI_NAMEs: LUTSENKO, SVETLANA  (contact)

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: absorption;Acetylation;Affect;American;Amino Acids;Animal Model;Animals;Apolipoproteins B;ATP Synthesis Pathway;Cells;Cessation of life;Chelating Agents;Chylomicrons;Complex;Copper;Coupled;Coupling;Cytoskeleton;Data;dietary;Dietary Fats;Disease;disorder control;Duodenum;Elderly;Endocytosis;Enterocytes;experience;experimental study;Fatty acid glycerol esters;Fatty Acids;Feedback;Food;Food Processing;Funding;Gastroenterology;Gastrointestinal Diseases;gastrointestinal function;gastrointestinal nutrient absorption;Gastrointestinal tract structure;Health;Hepatolenticular Degeneration;Homeostasis;Human;human disease;Impairment;in vivo;insight;Intestinal Diseases;Intestines;jejunum;Kinetics;Lateral;Link;lipid transport;Lipids;Lipoproteins;long chain fatty acid;Macromolecular Complexes;Measures;Membrane;Metabolic;Microtubules;Mitochondria;Modeling;Modification;Molecular;monolayer;mouse model;Mouse Strains;Mus;mutant;National Institute of Diabetes and Digestive and Kidney Diseases;novel strategies;Nuclear;Nutrient;nutrient absorption;particle;Pathway interactions;Patients;Persons;Physiological;Process;programs;protein complex;Protein Secretion;protein transport;Proteins;Proteome;Role;Sampling;Site;Site-Directed Mutagenesis;Small Intestines;Surveys;Testing;Tissues;Tomatoes;trafficking;Translating;Triglycerides;Tubulin;uptake;Work

PROJECT_TITLE: Molecular Mechanisms of Active Copper Transport

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Biotechnology;Cancer;Immunotherapy

PHR: PROJECT NARRATIVE All cells are coated with sugars, but cancer cells have altered sugar structures compared to their healthy counterparts. This project focuses on understanding how cancer cell-surface sugars contribute to disease progression, and on inventing new cancer therapies that target disease sugars.

PI_NAMEs: BERTOZZI, CAROLYN  (contact)

PROGRAM_OFFICER_NAME: COUCH, JENNIFER A

PROJECT_TERMS: Antibodies;antigen binding;bi-specific T cell engager;Binding;Biological;Bispecific Antibodies;cancer cell;Cancer Model;Cancer Patient;Cathepsins;Cell Adhesion;Cell Culture Techniques;Cell Proliferation;Cell surface;Cell Survival;Cell Therapy;Cells;checkpoint receptors;Chimera organism;Circulation;clinical translation;Dependence;Development;Disease;Disease Progression;Engineering;Family;Fc domain;Focal Adhesions;Funding;Glycocalyx;Glycoconjugates;Glycoproteins;glycosylation;Human;Human Engineering;Immune;Immune Cell Suppression;Immune Evasion;Immunologic Surveillance;Immunosuppression;Immunotherapy;invention;Knowledge;Lectin;Ligands;Malignant Neoplasms;Mediating;member;Modality;Modeling;Monoclonal Antibodies;mucinase;Mucins;Mus;Myeloid Cells;nanobodies;Neuraminidase;novel strategies;novel therapeutic intervention;overexpression;Patient-Focused Outcomes;Pattern;Peptide Hydrolases;Pharmacologic Substance;Phase II Clinical Trials;Phenotype;physical property;Polysaccharides;preclinical development;programs;Proliferating;receptor;response;sialic acid binding Ig-like lectin;Sialic Acids;Signal Transduction;Specificity;Structure;sugar;T-Cell Activation;T-Lymphocyte;targeted cancer therapy;Testing;Tumor Antigens;Work

PROJECT_TITLE: Targeting the cancer glycocalyx


NIH_SPENDING_CATS: Digestive Diseases;Infectious Diseases

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative This work will define new requirements for intraepithelial lymphocyte (IEL) homeostasis and function in the intestine. The work will establish the role of Gα13-coupled receptors in IEL using flow cytometric, cell signaling, imaging, and functional approaches. The mechanism by which Gα13 signaling controls the generation of IgA+ B cells in mesenteric lymph nodes will also be defined.

PI_NAMEs: CYSTER, JASON G (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Adhesions;ARHGEF1 gene;B-Lymphocytes;Bone Marrow;CCL25 gene;CCR9 gene;CD8B1 gene;Cell Communication;Cell Compartmentation;Cell Count;Cells;chemokine;chemokine receptor;Chemotaxis;Chimera organism;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Contact Tracing;Coupled;Cues;Data;Dendritic Cells;Dependence;differentiation in vitro;Disease;Dissection;draining lymph node;enteric pathogen;Epithelium;Excision;experimental study;firewall;fMet-Leu-Phe receptor;G-Protein-Coupled Receptors;Gene Expression Profiling;Gene Targeting;Generations;GPR18 receptor;GPR55 receptor;gut microbes;Hematopoietic;Heterotrimeric GTP-Binding Proteins;Homeostasis;Image;Immune;Immune system;Immune System Diseases;Immune Tolerance;Immunity;Immunoglobulin A;Immunoglobulin Class Switching;Immunoglobulin Switch Recombination;Immunosuppressive Agents;Individual;Infection;Inflammatory;Integrins;intestinal barrier;Intestines;intraepithelial;intravital imaging;Knock-out;knockout gene;Lamina Propria;Ligands;Lymphocyte;Lymphoid;Lymphoid Tissue;lysophosphatidylinositol;Mediating;mesenteric lymph node;microbiome;Microscopy;Molecular;Mucous Membrane;Mus;Myeloid Cells;pathogen;Peyer's Patches;Phenotype;Plasma Cells;Play;Population;Positioning Attribute;receptor;recruit;response;restraint;rho;Role;Signal Pathway;Signal Transduction;Small Intestines;Structure of germinal center of lymph node;System;T-Lymphocyte;Tamoxifen;Testing;therapy development;Thymus Gland;Tissues;Transforming Growth Factor beta;Tretinoin;Work

PROJECT_TITLE: Chemokines and Lymphoid Tissue Organization and Function

STUDY_SECTION: CMIA

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


NIH_SPENDING_CATS: Diabetes;Digestive Diseases;Liver Disease;Neurosciences;Nutrition;Obesity;Physical Activity;Prevention

PHR: PROJECT NARRATIVE Exercise improves metabolism throughout the body. We propose that exercise stimulates the brain, which then sends signals through the sympathetic nervous system to the liver and muscle to regulate glucose levels. The goal of this application is to investigate this inter-organ crosstalk and how it responds to exercise. We anticipate that the results from our investigation will aid in the development of novel therapies for diabetes.

PI_NAMEs: ELMQUIST, JOEL K. (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Adrenergic Agents;Adrenergic Receptor;beta-2 Adrenergic Receptors;Binding;Blood Circulation;Blood Glucose;blood glucose regulation;Body Weight decreased;Brain;Catabolism;Catecholamines;Cell Nucleus;Cell Respiration;Central Nervous System;combat;Development;diabetes mellitus therapy;diet-induced obesity;endurance exercise;Epinephrine;Exercise;exercise training;Genetic;Genetically Engineered Mouse;Gluconeogenesis;Glucose;glucose metabolism;glucose production;glycogenolysis;Goals;Hepatic;Homeostasis;Hormonal;Hypothalamic structure;improved;insight;Investigation;knock-down;lifestyle intervention;Liver;liver metabolism;Mediating;Metabolic;Metabolic Diseases;Metabolism;Methods;Modeling;Modification;mouse model;Mus;Muscle;Muscle Fibers;Neurons;Non-Insulin-Dependent Diabetes Mellitus;Norepinephrine;novel;novel therapeutics;Obese Mice;Obesity;Organ;Peripheral;Physical activity;Physiological;Play;PPAR gamma;Process;Protein Isoforms;receptor;Receptor Signaling;Regulation;response;Role;SF1;Signal Transduction;Skeletal Muscle;skeletal muscle metabolism;Sympathetic Nervous System;Testing;Tissues;transcription factor;uptake

PROJECT_TITLE: SF1 neurons and sympathetic regulation of glucose homeostasis

STUDY_SECTION: POMD

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Nanotechnology;Neurodegenerative;Neurosciences;Rare Diseases

PHR: PROJECT NARRATIVE Inherited retinal degenerations affect ~120,000 people in the USA and ~2.5 million world-wide. This project aims to validate lipid nanoparticle gene editing platforms in the retina of a large animal model, the non-human primate. These platforms will be used for the treatment of retinal degeneration.

PI_NAMEs: RYALS, RENEE CHRISTINE (contact)

PROJECT_TERMS: adaptive immune response;Address;Advanced Development;Affect;aged;Amyloidosis;Animal Model;Animals;Area;autosome;Bar Codes;Blindness;Blood;cell type;Cells;Clinical;Clinical Trials;clinically relevant;CRISPR/Cas technology;cytokine;Data;deep sequencing;design;Disease;Dose;Electroretinography;Encapsulated;endonuclease;Event;Family;FDA approved;gene augmentation therapy;gene editing technology;Gene Expression;Genes;genome editor;Genomics;Goals;Guide RNA;Harvest;Hour;Immune response;Immunofluorescence Immunologic;immunogenicity;improved;In Vitro;in vivo;Incidence;Individual;Inherited;inherited retinal degeneration;Injections;Innate Immune Response;insertion/deletion mutation;Investigation;knock-down;Knowledge;Leber's amaurosis;Libraries;Link;lipid nanoparticle;Liver;Macaca mulatta;Macrophage Activation;Measures;Mediating;Messenger RNA;Microglia;Modeling;Modification;Mus;Mutation;nanoparticle delivery;nonhuman primate;novel;Pathology;Patients;Pattern;Persons;Photoreceptors;Prealbumin;protein expression;Proteins;Retina;Retinal Degeneration;Retinal Dystrophy;Rhodopsin;Safety;Saline;Sampling;single-cell RNA sequencing;subretinal injection;Surface;T cell infiltration;Testing;Therapeutic;therapeutic genome editing;timeline;Tissues;Transfection;Translating;Viral Vector;Western Blotting

PROJECT_TITLE: Optimizing lipid nanoparticles for retinal gene editing in the NHP

STUDY_SECTION: INN

STUDY_SECTION_NAME: Innovations in Nanosystems and Nanotechnology Study Section [INN]


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

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

PHR: PROJECT NARRATIVE Dysregulated gene transcription is a major contributing factor in cancer, but the development of drugs interfering with general transcription remains a challenging task. The protein TAF1 is a component of the transcription machinery in eukaryotes, and TAF1 is a potential therapeutic target for acute myeloid leukemia (AML). This project aims at the development of first-in-class TAF1 targeting drugs for AML and other cancers that depend on TAF1 functionality for survival and proliferation.

PI_NAMEs: CHEN, JIANDONG ;LOPCHUK, JUSTIN MATTHEW;SCHONBRUNN, ERNST  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: Acute Myelocytic Leukemia;AML1-ETO fusion protein;Bromodomain;Cancer Biology;cancer cell;Cancer cell line;Cancer Model;cancer therapy;cell killing;Cell Proliferation;Cell Survival;Clinic;Clustered Regularly Interspaced Short Palindromic Repeats;cofactor;combat;Complex;Cryoelectron Microscopy;Data;design;Development;DNA Damage;Dose;drug development;Drug Targeting;efficacious treatment;efficacy study;Essential Genes;Eukaryota;FLT3 inhibition;Gene Expression;Genetic Transcription;Growth;Hematopoietic Neoplasms;Hematopoietic stem cells;immune modulating agents;Impairment;in vivo;Induction of Apoptosis;inhibitor;insight;kinase inhibitor;knock-down;Knock-out;knockout gene;Knowledge;Lead;leukemia treatment;Leukemic Cell;leukemogenesis;lymphoid neoplasm;Malignant Neoplasms;Metabolic;Methods;Modeling;Modification;molecular marker;Mus;mutant;Oncogenes;Oncogenic;patient derived xenograft model;Peptide Initiation Factors;Pharmaceutical Chemistry;Pharmacodynamics;Proliferating;Property;Protac;Proteins;Proteomics;Regulation;Reporting;Research;Research Personnel;RNA Interference;RNA Polymerase II;Role;Scientist;screening;Series;Signal Transduction;small hairpin RNA;small molecule inhibitor;structural biology;Structure;synergism;TAF1 gene;Therapeutic;therapeutic target;Toxic effect;TP53 gene;transcription factor;Transcription Initiation;Treatment Efficacy;treatment response;tumor;tumor xenograft;vector;X-Ray Crystallography

PROJECT_TITLE: Selective targeting of TAF1 function in acute myeloid leukemia

STUDY_SECTION: DMPC

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology C Study Section[DMPC]


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

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: The aging brain is associated with increased risk of developing postoperative delirium (POD), postoperative neurocognitive disorder, and Alzheimer’s disease. POD occurs in 9-50% older patients undergoing anesthesia and surgery, and is associated with high risk of developing Alzheimer’s Disease and Related Dementias (ADRD), worse clinical outcomes, and higher mortality. This proposal uses multidisciplinary tools including intravital multi- photon imaging, genetic manipulation, biochemistry, and animal behavior, to dissect a previously unknown role for PNNs in the pathogenesis of POD, which provides novel mechanistic insights and therapeutic targets for POD, a condition related to ADRD.

PI_NAMEs: SHEN, SHIQIAN  (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Ablation;age related;Agglutinins;aging brain;Alzheimer's Disease;Alzheimer's disease related dementia;Anesthesia procedures;Animal Behavior;Attention;Attenuated;Behavior;Binding;Biochemical;Biochemistry;Biological Markers;Biomechanics;Calcium;Cd68;Cells;Cerebrum;Chondroitin ABC Lyase;Chondroitin Sulfate Proteoglycan;Clinical;Communication;Cues;Data;Dendrites;Development;Environment;Enzymes;excitatory neuron;Extracellular Matrix;Genetic;genetic manipulation;high risk;Hippocampus;Image;Immunofluorescence Immunologic;Incidence;inhibitor;inhibitory neuron;insight;Interneuron function;Interneurons;Kinetics;Lectin;Link;link protein;Liquid substance;Macrophage;Macrophage Colony-Stimulating Factor Receptor;Mediating;Memory;Mental disorders;Microglia;monocyte;mortality;multi-photon;multidisciplinary;multiphoton imaging;multiphoton microscopy;Mus;Nerve Degeneration;neurocognitive disorder;Neuroglia;neuroinflammation;neuronal cell body;Neuronal Dysfunction;Neuronal Plasticity;Neurons;novel;old mice;older patient;Operative Surgical Procedures;Outcome;overexpression;painful neuropathy;Parvalbumins;Pathogenesis;perineural;Photons;Postoperative Complications;postoperative delirium;Postoperative Period;preservation;prevent;Receptor Signaling;Research;Resolution;Risk;Role;scaffold;Stains;Structure;Sulfate;Tamoxifen;tau Proteins;tau-1;Testing;therapeutic target;three photon microscopy;tool;Visualization;Wait Time;Wisteria

PROJECT_TITLE: Neuroinflammation, Perineural Nets, and Postoperative Delirium

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]