NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Macular Degeneration;Neurodegenerative;Neurosciences

ORG_CITY: DURHAM

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Narrative Age-related macular degeneration (AMD) affects 30% of individuals over the age of 65 years and is the leading cause of vision loss in the Western World. Though the fundamental abnormalities causing AMD development are not known, several pathogenic pathways altered in AMD have been identified including inflammation, RPE and choroidal degeneration, and RPE barrier dysfunction, among others. The objective of this grant is to perform the first characterization of the roles of the different isoforms of the matricellular protein, osteopontin (OPN), in RPE cells a function of age, and asks the question would targeting OPN be a therapeutic option for dry AMD, using mouse models that present with AMD – like features.

PI_NAMEs: MALEK, GOLDIS  (contact)

PROGRAM_OFFICER_NAME: GORDIYENKO, NATALIYA

PROJECT_TERMS: Affect;Age;Age related macular degeneration;Aging;Animal Model;Anti-Inflammatory Agents;Apoptosis;Atrophic;Autophagocytosis;Biochemical;Biology;Blindness;Blood-Retinal Barrier;Cell Differentiation process;Cell Physiology;Cell secretion;Cells;Cellular Metabolic Process;Characteristics;Complex;Contrast Sensitivity;cytokine;Data;Deposition;design;Development;Disease;Drusen;efficacy testing;Elderly;Epidemiology;Etiology;Exposure to;extracellular;Eye;Functional disorder;gain of function;Genetic;Glycoproteins;Goals;Grant;Health;Homeostasis;Human;human old age (65+);Immune;Impairment;In Vitro;in vitro Model;in vivo;in vivo Model;Individual;Inflammation;Inflammatory;Injury;Knowledge;Link;Lipids;loss of function;Macrophage;Metabolism;Microglia;Molecular;Monitor;Morphology;mouse model;Names;Neurodegenerative Disorders;Nonexudative age-related macular degeneration;osteopontin;Oxidants;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Phagocytosis;Pharmaceutical Preparations;Phenotype;phenotypic biomarker;photoreceptor degeneration;Pigment Epithelium;Plasma;Play;prevent;Process;Property;Protein Isoforms;Proteins;Publishing;recruit;Reporting;Retina;RNA Splicing;Role;Side;Signal Pathway;source localization;stressor;Structure of retinal pigment epithelium;System;Systemic disease;Testing;Therapeutic;Therapeutic Effect;therapeutic evaluation;Therapeutic Use Study;Tissue Donors;Tissues;transdifferentiation;Variant;Western World

PROJECT_TITLE: Deciphering the role of osteopontin in the aging eye and age-related macular degeneration

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


ADMINISTERING_IC: DE

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Pediatric;Prevention

ORG_CITY: AMHERST

ORG_COUNTRY: UNITED STATES

ORG_DEPT: DENTISTRY

ORG_FIPS: US

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: Project Narrative Despite the wealth of biological knowledge about how teeth are formed, the underlying molecular mechanisms of tooth development remain poorly understood. This research will identify the gene regulation programs of tooth enamel development and address the question of why certain genetic mutations result in congenital dental enamel anomalies. Understanding the gene regulation programs of tooth enamel development is important for the development of better strategies for the diagnosis, prevention, and treatment of congenital and acquired dental disorders.

PI_NAMEs: KWON, HYUK JAE EDWARD (contact)

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: Address;Ameloblasts;Amelogenesis;Automobile Driving;Binding;Biological;causal variant;Cell Differentiation process;cell fate specification;Cell Lineage;Cell Proliferation;Cells;ChIP-seq;Chromatin;Clinical;comparative;Competence;Congenital Disorders;Data;Data Set;Dental;Dental Enamel;dental infection;Development;Diagnosis;differential expression;Disease;DNA Sequence Alteration;Dysplasia;Ectodermal Dysplasia;embryonic stem cell;Enamel Formation;Enamel Organ;Environment;Epigenetic Process;epigenomics;Event;experimental study;Family;Gene Expression Regulation;gene regulatory network;Gene set enrichment analysis;Genes;Genetic;genetic signature;Genetic Transcription;Genomics;Genotype;Germ Lines;Goals;Health;Homeostasis;Human;human disease;Incisor;Individual;Infant;Investigation;Knock-out;Knockout Mice;Knowledge;Left;Light;loss of function mutation;malformation;Methods;mineralization;Molecular;Morphogenesis;mouse model;multiple omics;Mus;Mutation;novel therapeutics;Oral health;organ growth;Organogenesis;Pathogenicity;Pathologic;Patients;Penetrance;Personal Satisfaction;Phenotype;prevent;Prevention;programs;Protein Isoforms;Publishing;Quality of life;Reporting;Research;response;Role;Salivary Glands;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Skin;socioeconomics;System;Temporomandibular Joint;Testing;TFAP2A gene;Therapeutic;Tissues;Tooth Diseases;Tooth Germ;Tooth structure;Toothache;TP53 gene;transcription factor;transcription regulatory network;transcriptome;transcriptome sequencing;Work

PROJECT_TITLE: Genomic and functional investigations of the transcriptional regulatory network of tooth enamel development

STUDY_SECTION: ODCS

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


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: This project is to investigate the molecular processes that control the association of protein tyrosine kinases with other cellular proteins. Dysregulation of these associations can lead to aberrant function in immunological response, cell proliferation or cell survival, and lead to disease including autoimmune disorders and cancer. The value of the research is to provide knowledge that can be used to either fuel future efforts to understand disease through biosensors or develop effective drugs against autoimmune disease or metastatic cancer.

PI_NAMEs: POST, CAROL B. (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Affinity;Amino Acid Sequence;Animal Model;Antineoplastic Agents;Autoimmune Diseases;Binding;biophysical analysis;Biophysics;Biosensor;C-terminal;Catalytic Domain;Cell Physiology;Cell Proliferation;Cell Survival;Cells;Chemicals;Clinical;Complex;Computer Simulation;Cytoplasm;Databases;Disease;Disseminated Malignant Neoplasm;DNA;Docking;drug development;Drug usage;Electrostatics;enthalpy;Entropy;Enzymes;Event;Exhibits;experimental study;Future;G-Protein-Coupled Receptors;Genes;Health;Human;Immune response;Immunologic Receptors;improved;In Vitro;inhibitor;ITAM;Knowledge;Libraries;Ligands;Malignant Neoplasms;Mediating;Membrane;Methods;Microscopic;Molecular;molecular dynamics;Motion;Outcome;Pattern;peptide structure;Peptides;Pharmaceutical Preparations;Phosphorylation;Phosphotransferases;Play;polypeptide;Post-Translational Protein Processing;Process;protein complex;Protein Conformation;Protein Kinase;protein protein interaction;Protein Region;Protein Tyrosine Kinase;Protein-Serine-Threonine Kinases;Proteins;receptor;recruit;Research;Role;Sampling;Scientific Advances and Accomplishments;screening;Serine;Side;Signal Pathway;Signal Transduction;Signaling Protein;Site;small molecule;src Homology Region 2 Domain;src-Family Kinases;Structure;Substrate Interaction;SYK gene;Thermodynamics;three dimensional structure;Tyrosine Kinase Inhibitor;Tyrosine Phosphorylation

PROJECT_TITLE: NMR Structure of Peptide and Protein Complexes

STUDY_SECTION: MSFB

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Narrative Obesity induces chronic inflammation that triggers cellular damage involving multiple organs, possibly by damaging reparative cells that reside in tissues. We will test the hypothesis that obesity in human subject induces injury to fat tissue-derived reparative cells, which interferes with their capacity to mend injured mouse microvessels.

PI_NAMEs: EIRIN, ALFONSO ;LERMAN, LILACH O (contact)

PROGRAM_OFFICER_NAME: REID, DIANE M

PROJECT_TERMS: Address;Adipose tissue;Age;angiogenesis;Attenuated;bariatric surgery;Biological Models;Blood Vessels;Bobcat;Body Weight decreased;Bone Marrow;Cardiovascular Diseases;cardiovascular risk factor;cell injury;Cell Physiology;Cells;Chronic;citrate carrier;Clinical;Cost Savings;critical limb Ischemia;Cytosine;Diabetes Mellitus;Down-Regulation;effective therapy;Endocrine;Endothelial Cells;Enhancers;Enzyme Inhibitor Drugs;Epidemic;Epigenetic Process;Event;Exhibits;falls;Family suidae;Fatty acid glycerol esters;Functional disorder;Functional impairment;Gene Expression;Gene Targeting;Genes;Harvest;Histones;Human;human subject;Impairment;improved;In Vitro;in vivo;in vivo imaging;Inflammation;injured;Injury;injury recovery;Ischemia;Kidney;Kidney Diseases;Life Style Modification;Link;Magnetic Resonance Imaging;Mediating;Mesenchymal;Metabolic;Methods;Methylation;microCT;MicroRNAs;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Modification;mortality risk;mouse model;Mus;neutralizing antibody;novel;obese patients;Obesity;Organ;paracrine;Pathogenesis;Patients;Peptide antibodies;Peptides;Peripheral;Peripheral arterial disease;Peripheral Vascular Diseases;Plasma;Predisposition;Prevalence;Process;promoter;Property;protective effect;protein expression;Quality of life;Regulation;Renal Artery Stenosis;repair function;repaired;reparative capacity;restoration;Role;Sampling;Secondary to;stem;Stromal Cells;Structure;System;Techniques;Testing;Therapeutic;Thinness;tissue repair;Tissues;tool;transcriptome sequencing;Vascular Diseases

PROJECT_TITLE: Obesity-induced dysfunction of human MSC in peripheral microvascular repair

STUDY_SECTION: IVPP

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


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Biotechnology;Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Parkinson's Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Transplantation

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE There is great enthusiasm about the regenerative potential of grafting dopamine neurons derived from stem cells into the brains of patients with Parkinson's disease (PD). But there are concerns about the negative impact of the abnormal proteins and inflammation in the Parkinson brain on graft survival. Here we analyze inflammation in brain cells and in human grafts injected into the brain of α-synuclein mouse models of PD; we also develop gene editing methods to enhance the resistance of graft cells to neurotoxicity due to inflammation.

PI_NAMEs: TABAR, VIVIANE  (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, LUIS FLANAGAN

PROJECT_TERMS: Ablation;alpha synuclein;Animal Model;Animals;Anti-Inflammatory Agents;Astrocytes;base editing;Behavior;Behavioral;Bilateral;Brain;brain cell;Brain region;Candidate Disease Gene;Cell Lineage;Cells;cellular engineering;Clinic;clinical lot;Clinical Trials;Collaborations;combinatorial;Complex;Corpus striatum structure;CSF1R gene;Data;Deposition;Derivation procedure;Deterioration;Development;Disease;disease model;Disease Progression;DNA;Dopamine Agonists;dopamine graft;dopaminergic neuron;Environment;Exhibits;Experimental Designs;Gene Expression Alteration;Gene Modified;gene-editing approach;Generations;Genes;glial activation;graft function;Graft Survival;Histologic;Human;human embryonic stem cell;Human Engineering;immunodeficiency;immunoregulation;in vivo;Inflammation;inhibitor;Injections;Lewy Bodies;life span;Longitudinal Studies;Maps;Microglia;Midbrain structure;mitochondrial dysfunction;Modeling;monomer;Motor;motor symptom;mouse model;mouse synuclein alpha;Mus;mutant;Mutation;Natural regeneration;Nature;Nerve Degeneration;Neurodegenerative Disorders;Neuroglia;neuroinflammation;neuron loss;Neuronal Dysfunction;neuronal survival;Neurons;neuropathology;neuroprotection;neurotoxic;neurotoxicity;neurotransmission;novel;Parkinson Disease;pars compacta;Pathogenesis;Pathogenicity;Patients;Persons;Phase I Clinical Trials;Phenotype;Population;pre-formed fibril;predictive modeling;prion-like;Proteins;regeneration potential;Regenerative Medicine;Research;Resistance;Resistance development;restoration;Role;Safety;Signal Transduction;SNCA gene;stem cells;Substantia nigra structure;synucleinopathy;Techniques;Technology;Testing;Therapeutic;Time;tool;Toxic effect;transcriptomics;transmission process

PROJECT_TITLE: Human Dopamine Grafts in Alpha-Synuclein Models of Parkinson Disease

STUDY_SECTION: CDIN

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


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: PITTSBURGH

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: The adenosine (ADO) pathway is a key mechanism by which the body regulates inflammation. Our preliminary results in different nonhuman primate species in which SIV infection has an opposite outcome have shown that, in the nonprogressive SIV infections, in which the gut damage and chronic inflammation are well controlled, there are higher levels of ADO in the gut tissues compared the progressive infections, which associate loss of gut integrity and dramatic increases in inflammatory biomarkers upon SIV infection. These findings strongly support a significant involvement of the ADO pathway in the pathogenesis of SIV/HIV related gut dysfunction. We will probe this hypothesis in nonhuman primates, in which we will therapeutically increase ADO production with Roxadustat. If successful, our experiments may be directly translated as a new therapeutic strategy to alleviate SIV/HIV-related gut damage and residual inflammation that are responsible for multiple comorbidities.

PI_NAMEs: VASILE PANDREA, IVONA  (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: Abbreviations;adaptive immune response;Address;Adenosine;adenosine deaminase;Adenosine Kinase;Adenosine Monophosphate;adenosine transporter;Adenosine Triphosphate;African Green Monkey;antiretroviral therapy;Biological Assay;Biological Markers;Cardiovascular Diseases;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell surface;Characteristics;Chronic;chronic infection;Circulation;Clinical;comorbidity;Data;Development;Dipyridamole;DNA;Down-Regulation;ecto-nucleotidase;Environment;Enzymes;Excision;experimental study;extracellular;Female;Frequencies;Functional disorder;Future;gut health;Gut Mucosa;HIV;HIV Infections;immune activation;immunoregulation;improved;Individual;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory modulation;Inflammatory Response;inhibitor;Innate Immune Response;innovation;Inosine;Intervention;Intestines;Laboratories;Liquid Chromatography;Macaca nemestrina;male;microbial;microbial products;Modeling;mucosal site;Mucous Membrane;new therapeutic target;Nicotinamide adenine dinucleotide;nonhuman primate;novel therapeutic intervention;Nucleosides;Outcome;Pathogenesis;Pathogenicity;Pathway interactions;peripheral blood;Persons;Play;preservation;Prevalence;prevent;Procollagen-Proline Dioxygenase;Production;Prognosis;Purinergic P1 Receptors;Regulatory T-Lymphocyte;Residual state;Role;Signal Pathway;Signal Transduction;SIV;Source;systemic inflammatory response;T cell reconstitution;T-Cell Activation;Testing;Therapeutic;Therapeutic Intervention;Tissues;Translating;trend;Up-Regulation;Viral reservoir;Viremia;Virus Replication

PROJECT_TITLE: Probing the role of adenosine pathway in SIV pathogenesis

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

ORG_CITY: CHAPEL HILL

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE The recent and rapid advancement of genome-wide technologies has enabled major breakthroughs in heart, lung, and blood (HLB) research. Yet, we continue to face a deficit in interdisciplinary and collaborative HLB genetic epidemiologists who can address the challenges and opportunities characterizing today's wide and expanding genomics knowledge base and threats to HLB health. Our internationally known mentors with established research collaborations, unique and multidisciplinary training environment, and innumerable research opportunities make us exceptionally well-positioned to continue to develop the next generation of genetic epidemiology leaders who are well-equipped to investigate the genetic underpinnings and public health challenges of HLB traits and associated diseases.

PI_NAMEs: MOHLKE, KAREN L.;NORTH, KARI E. (contact)

PROGRAM_OFFICER_NAME: COADY, SEAN

PROJECT_TITLE: The Genetic Epidemiology of Heart, Lung, and Blood Traits Training Grant (GenHLB)

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(JA)]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Autoimmune Disease;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: We will be examining the role of Müller glial cells and the process of autophagy in maintaining the immune privilege in the eye. Combining studies on immune privilege, autophagy with Müller cell biology is a novel approach to understanding retinal disease.

PI_NAMEs: FERGUSON, THOMAS ALMON (contact)

PROJECT_TERMS: Ablation;Anti-Inflammatory Agents;antigen-specific T cells;arm;Autoimmune Diseases;autoimmune uveitis;Autoimmunity;Autophagocytosis;Bacteria;Biological Process;Blindness;Blood-Retinal Barrier;cell injury;Cell Physiology;Cells;Cellular biology;cytokine;Data;Degradation Pathway;Development;Disease;disease model;Eating;Elements;Endotoxins;extracellular;Eye;Eye diseases;Failure;Genes;Homeostasis;Immune;Immune response;Immune system;immunoregulation;Infection;Inflammation;Inflammatory;Inflammatory Infiltrate;Inflammatory Response;Keratoplasty;Ligands;Macrophage;Mediating;Minor;Mitochondria;Modeling;Molecular;Morphology;Muller's cell;Mus;Nature;Neuroglia;neuroprotection;Neurotransmitters;novel;novel strategies;Organ;Participant;Pathogenicity;Pathway interactions;Phagocytes;Phagocytosis;Photoreceptors;prevent;Process;Production;Property;protein aggregation;Reaction;Recycling;Resistance;response;Retina;retinal damage;Retinal Degeneration;Retinal Diseases;Role;single-cell RNA sequencing;Site;Stress;System;T cell response;T-Cell Receptor;Testing;Thick;Tissues;Toll-like receptors;Uveitis;virtual;Virus Diseases;Vision;visual cycle;Vitamin A

PROJECT_TITLE: Immune Privilege, Müller cells, and Autophagy


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Liver Disease

ORG_CITY: Chicago

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The overall goal of this project is to implement a series of engineered liver culture platforms for analyzing the microenvironmental regulation of human liver cell functions and epigenetic changes within the context of non- alcoholic fatty liver disease (NAFLD). This approach will enable unique studies focused on the synergistic effects of extracellular matrix composition and stiffness, multicellular interactions, and soluble triggers of NAFLD in cellular phenotypic alterations, which could aid the development of novel drug therapies for this disease.

PI_NAMEs: KHETANI, SALMAN R (contact);UNDERHILL, GREGORY H

PROGRAM_OFFICER_NAME: BURGESS-BEUSSE, BONNIE L

PROJECT_TERMS: 3-Dimensional;adverse outcome;Affect;Animal Model;Antibodies;ATAC-seq;Biochemical;Cell Communication;Cell Physiology;cell type;Cells;cellular targeting;Cirrhosis;Clinical;Coculture Techniques;combinatorial;Cues;Data;Data Set;Development;Disease;Disease Outcome;Disease Pathway;drug metabolism;Drug Screening;Endothelial Cells;Engineering;Epidemic;Epigenetic Process;Exposure to;extracellular;Extracellular Matrix;Extracellular Matrix Proteins;Fatty Acids;FDA approved;Fibrosis;Fructose;Gene Expression Profile;Genes;Glucose;Goals;Hepatic Stellate Cell;Hepatocyte;Human;human model;Hydrogels;improved;In Vitro;Individual;Inflammation;innovation;insight;Insulin;Investigation;Kupffer Cells;Liver;liver biopsy;Liver diseases;Liver Dysfunction;Liver Fibrosis;Mechanics;Mediator;metabolic-associated fatty liver disease;Microfluidics;Modification;Myofibroblast;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;Normal Range;novel;novel therapeutics;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Physiological;Primary carcinoma of the liver cells;Publishing;quantitative imaging;Regulation;response;Role;screening;Series;Signal Transduction;Single Nucleotide Polymorphism;Stimulus;System;Testing;Therapeutic;Tissue Engineering;Tissues;tool;transcription factor;transcriptome sequencing;Work

PROJECT_TITLE: Synergistic effects of ECM and heterotypic crosstalk on cellular responses in non-alcoholic fatty liver disease

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Nutrition;Prevention

ORG_CITY: PISCATAWAY

ORG_DEPT: NUTRITION

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

ORG_STATE: NJ

PHR: PROJECT NARRATIVE The goal of this proposal is to test a novel hypothesis to explain how excess exposure to folic acid can exacerbate vitamin B12 deficiency. The results will inform future research to determine the acute and long- term health effects of depleted B12 status resulting from high folic acid intakes in populations exposed to folic acid fortification and use of folic acid-containing supplements.

PI_NAMEs: JACQUES, PAUL F;MILLER, JOSHUA WILLIAM (contact)

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: Acute;Address;Age;Aging;Anemia;Biochemical;Biological Markers;Blood;Characteristics;Circulation;Clinical;cohort;Cohort Studies;Creatinine;Data;dihydrofolate;Dihydrofolate Reductase;Dose;Enzymes;Epidemiology;epidemiology study;Erythrocytes;Ethnic Origin;experience;Exposure to;Folic Acid;Folic Acid Deficiency;Folic acid fortification;folic acid supplementation;Fortified Food;Goals;Health;Hematology;Hematopoietic;Homocysteine;Human;Hyperhomocysteinemia;Impaired cognition;improved;Individual;Institution;Intake;Intervention Studies;Investigation;Kidney;Linear Regressions;Masks;Measurement;Megaloblastic Anemia;Metabolic;Methylmalonic Acid;Morbidity - disease rate;mortality;National Health and Nutrition Examination Survey;Neural Tube Defects;Neurologic;Neurologic Symptoms;novel;Observational Study;Output;Participant;Patients;Pernicious Anemia;Persons;Plasma;Population;Predisposition;Prevalence;programs;Public Health;Race;Relapse;relapse patients;Renal function;Risk;Risk Reduction;Serum;sex;success;Symptoms;System;Testing;Tetrahydrofolates;Tissues;United States;urinary;Urine;Validation;Vitamin B 12;Vitamin B 12 Deficiency;Vitamins

PROJECT_TITLE: The High Folate/Low Vitamin B12 Interaction is a Novel Cause of Vitamin B12 Depletion: Testing a New Hypothesis

STUDY_SECTION: KEDD

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


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Pediatric;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: WORCESTER

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: PROJECT NARRATIVE Structural racism is embedded in societal structures that limit opportunities and resources for racialized groups; this manifest as social determinants of health (SDOH)—the social circumstances in which people are born, live, and age—and as racial/ethnic health inequities. While healthcare systems that serve low-income patients are implementing SDOH screening, critical knowledge gaps remain regarding the equitable implementation and impact of SDOH screening/referral systems. We will apply an antiracism lens to an evidence-based SDOH screening/referral system and develop an antiracist-informed implementation toolkit aimed at mitigating unequal treatment for patients of color in both the healthcare and social service systems as well as evaluate the impact of the SDOH screening/referral system on mitigating deleterious chronic disease outcomes across the lifespan; this proposal will allow us to create novel community- and patient-engaged strategies for implementing SDOH screening/referral systems that can be disseminated across the country with the potential to reduce racial/ethnic health inequities.

PI_NAMEs: GARG, ARVIN  (contact)

PROGRAM_OFFICER_NAME: GODETTE, DIONNE

PROJECT_TERMS: Academy;Address;Adult;Age;American;anti-racism;Asian;Asthma;Black race;Caregivers;Childhood;Chronic Disease;Clinic;Clinical;Color;Communities;community engaged approach;Country;design;Diabetes Mellitus;Discrimination;Disease Outcome;Effectiveness;effectiveness evaluation;effectiveness-implementation RCT;effectiveness/implementation hybrid;effectiveness/implementation study;Equity;ethnic diversity;ethnic health disparity;Ethnic Origin;evidence base;experience;Face;Family;Family Physicians;Family Practice;food insecurity;Goals;Health;health care delivery;health care service;health disparity;health equity;health inequalities;Health system;Healthcare Systems;Hyperlipidemia;Hypertension;implementation evaluation;implementation outcomes;implementation protocol;implementation strategy;improved;Individual;Inequity;informant;Institution;Insurance Carriers;Intervention;Interview;Knowledge;Latinx;Lead;lens;Life Cycle Stages;life span;Low income;lower income families;Massachusetts;Medicaid;Medical;Medicine;Mental Depression;minority patient;Mission;National Institute on Minority Health and Health Disparities;Neighborhood Health Center;novel;organizational structure;Outcome;patient engagement;patient oriented;Patients;Pediatrics;people of color;Persons;programs;Protocols documentation;Race;racial diversity;racial health disparity;racial population;racism;Research;Research Personnel;Resources;screening;screening guidelines;social;social health determinants;social stigma;Social Work;Strategic Planning;Structural Racism;Structure;System;tool;United States;uptake;Work

PROJECT_TITLE: Improving Chronic Disease Outcomes Across the Lifespan by Addressing Structural Racism


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Infectious Diseases;Neurosciences;Orphan Drug;Osteoporosis;Rare Diseases

ORG_CITY: CHARLOTTE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF NORTH CAROLINA CHARLOTTE

PHR: Project Narrative Bone disorders resulting from bacterial infection are associated with severe inflammation and bone loss and/or abnormal bone formation but the mechanisms underlying such damage are poorly understood. While the neuropeptide substance P is recognized to exacerbate inflammation in a range of tissues, its role in the damage associated with bacterial infections of bone tissues has not been examined. In these studies, we will determine whether inhibiting the substance P receptor can attenuate bacteria-induced bone damage, providing an essential step in evaluating the therapeutic potential of repurposing clinically approved substance P receptor antagonists as an adjunctive therapy to limit inflammatory bone loss.

PI_NAMEs: JOHNSON, MORGAN BRITTANY;MARRIOTT, IAN  (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Acute;Address;Affinity;Animal Model;antagonist;Anti-Inflammatory Agents;anti-microbial drug;Attenuated;Bacteria;Bacterial Infections;Biological;Biological Response Modifiers;bone;bone cell;Bone Diseases;bone loss;Bone remodeling;Bone Resorption;Bone Tissue;Cells;Central Nervous System;Chemotactic Factors;Clinical;clinically relevant;Dendritic Cells;Development;Diagnosis;Disease;experimental study;FDA approved;Gastrointestinal tract structure;Genus staphylococcus;Goals;Human;human model;Immune;immune function;improved;In Vitro;in vivo;Incidence;Infection;Inflammation;Inflammation Mediators;Inflammatory;inflammatory bone loss;inhibitor;Leukocytes;Macrophage;Maintenance;Mediating;Mediator;Microbe;microbial;mouse model;Mus;Myeloid Cells;Nerve Fibers;nerve supply;Neuropeptide Receptor;Neuropeptides;neutrophil;Organism;Osteitis;Osteoblasts;Osteoclasts;Osteocytes;Osteogenesis;osteogenic;Osteolytic;Osteomyelitis;pathogenic microbe;Performance;Peripheral;Physiological;Play;preclinical evaluation;Production;prophylactic;Prophylactic treatment;recruit;Regulation;Research;response;Role;Sensory;Severities;Severity of illness;Site;Skin;Staphylococcus aureus;Substance P;Tachykinin;TACR1 gene;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Tissues;Work

PROJECT_TITLE: Substance P exacerbation of staphylococcal bone damage

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Sleep Research

ORG_CITY: MIAMI

ORG_NAME: FLORIDA INTERNATIONAL UNIVERSITY

ORG_STATE: FL

PHR: PROJECT NARRATIVE Abnormal neural synchrony between the medial prefrontal cortex and hippocampus is a key feature of several pathophysiological and cognitive brain disorders including but not limited to schizophrenia, Alzheimer's disease, and epilepsy, thus understanding how prefrontal-hippocampal interactions are supported at the circuit level can have a significant impact on public health. Nucleus reuniens (RE) of the midline thalamus is thought to drive coherent neural states between the medial prefrontal and the hippocampus during wake and sleep states, however, this idea remains experimentally untested. The proposed research will explore the excitatory actions of RE pathway-specific neurons on the coherent activity of the prefrontal-hippocampal circuit during an episodic-like sequence memory task, and during theta and delta driven rhythms in sleep (REM/NREM) to determine how RE influences those interactions in support of memory and behavior.

PI_NAMEs: VIENA, TATIANA DANELA (contact)

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: Alzheimer's Disease;Anatomy;Arousal;Automobile Driving;Award;Behavior;Behavioral;Brain;Brain Diseases;career;Cells;Cognition;Cognitive;Decision Making;Dimensions;Electrophysiology (science);Epilepsy;episodic like memory;Equipment;Event;excitatory neuron;experimental study;Fire - disasters;Florida;Foundations;Frequencies;frontal lobe;Future;Generations;Glutamates;Goals;Hippocampus;Hispanic-serving Institution;International;Knowledge;Laboratories;Learning;Link;Medial;medial temporal lobe;Mediating;Memory;memory consolidation;Mental disorders;Mentors;Methodology;Monitor;Nervous System Disorder;neural;Neurons;neurophysiology;non rapid eye movement;Odors;Optics;optogenetics;Pathway interactions;Performance;Periodicity;Phase;Physiologic pulse;Physiological;Play;Population;Positioning Attribute;Pre-Clinical Model;Prefrontal Cortex;Principal Investigator;Process;Program Development;programs;Public Health;Rattus;REM Sleep;Research;Research Personnel;Resources;Reuniens Thalamic Nucleus;Rodent;Role;role model;Running;Sampling;Schizophrenia;Scientist;Shapes;Site;skills;Sleep;success;Symptoms;System;Technical Expertise;Testing;Thalamic structure;theories;therapeutic target;Theta Rhythm;Time;Training;Underrepresented Students;Universities

PROJECT_TITLE: Nucleus reuniens of the thalamus as a target for driving network-wide memory states


ED_INST_TYPE: SCHOOLS OF OPTOMETRY/OPHT TECH

NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Prevention

ORG_NAME: STATE COLLEGE OF OPTOMETRY

PHR: Project Narrative The proposed research is relevant to public health because it aims to identify early diagnostic markers of glaucoma in myopic eyes with the goal to accelerate the development of new prevention, diagnostic and treatment strategies and prevent glaucomatous visual impairment in myopic eyes. The project is relevant to the NEI's mission because, by addressing the unknown nature of the relationship between myopia and glaucoma, the results will have the potential to reduce vision loss and improve the quality of life of the rising numbers of myopic patients with associated glaucomatous degeneration.

PI_NAMEs: BENAVENTE-PEREZ, ALEXANDRA  (contact)

PROGRAM_OFFICER_NAME: SONG, HONGMAN

PROJECT_TERMS: Acceleration;Acute;Address;Affect;Anatomy;Animal Model;Architecture;Astrocytes;axon injury;axonal degeneration;Blindness;cardiovascular disorder risk;Cell Count;Cell Physiology;Cell Survival;Cells;Complex;Connexin 43;Coupling;Data;Detection;Development;Diagnosis;diagnostic biomarker;diagnostic strategy;early detection biomarkers;Early identification;Epidemic;Epidemiologist;Etiology;Exhibits;experience;Exposure to;Eye;Functional disorder;ganglion cell;Genetic;Genetic Markers;Glaucoma;glial activation;Goals;Growth;Health Professional;Human;hypertensive;Impairment;improved;Individual;innovation;Intervention;Investigational Therapies;Link;Masks;mechanical stimulus;Mechanical Stress;Mechanics;mechanotransduction;Microglia;Mission;Modeling;Molecular;Myopia;Nature;Neuroglia;Neuropathy;neuroprotection;nonhuman primate;novel;Optic Disk;Outcome;Patients;Pattern;Perception;pharmacologic;Population;Predisposition;pressure;Prevalence;prevent;Prevention strategy;Progressive Myopia;Public Health;Quality of life;Research;response;Retinal Ganglion Cells;Risk;Scientist;Secondary to;Signal Pathway;Signal Transduction;Smoker;stressor;Stretching;Stroke;Testing;Therapeutic;therapeutic target;Thick;Thinness;Time;Tissues;tool;treatment strategy;Vision;Visual impairment

PROJECT_TITLE: Myopia and Glaucoma, Linked via Mechanotransduction Mechanisms Affecting the Ganglion Cell Complex

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 2 Study Section[PED2]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: LA JOLLA

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: NARRATIVE Ovarian cancer recurrence is a leading cause of cancer deaths among women due to tumor resistance to therapy. The tumor microenvironment is highly immunosuppressive, and this constitutes a major treatment barrier. Utilizing our newly-developed and highly characterized murine models of ovarian cancer and patient- derived tumors, we will systematically examine the molecular mechanisms and targets associated with FAK- dependent oncogenic signals reprogramming the tumor microenvironment promoting tumor immune evasion.

PI_NAMEs: SCHLAEPFER, DAVID D (contact)

PROGRAM_OFFICER_NAME: MERCER, NATALIA

PROJECT_TERMS: Antibodies;Antigens;Ascites;Automobile Driving;Bioinformatics;Cancer Etiology;cancer infiltrating T cells;Cancer Model;cancer recurrence;Cause of Death;CCL2 gene;CD8-Positive T-Lymphocytes;CD8B1 gene;cell motility;Cells;chemokine;Chemoresistance;chemotherapy;Chromosomes;Combination immunotherapy;combinatorial;Complement;cyclooxygenase 2;cytokine;Disease;effector T cell;Endothelial Cells;Etiology;Exhibits;Focal Adhesion Kinase 1;gain of function;Gene Amplification;Genes;Genetic;genetic regulatory protein;Goals;Growth;Hypoxia;Immune;immune checkpoint;Immune Evasion;Immune signaling;Immunoassay;immunodeficiency;Immunosuppression;Immunotherapy;Implant;In Vitro;in vivo;inducible gene expression;Infiltration;insight;ITIM;kinase inhibitor;Knock-out;Knockout Mice;Knowledge;KRAS2 gene;Leukocytes;Link;loss of function;LoxP-flanked allele;Malignant - descriptor;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Membrane Proteins;Messenger RNA;Modeling;Molecular;Molecular Analysis;Molecular Conformation;mouse model;Mus;Myeloid-derived suppressor cells;nano-string;nectin;neoplastic cell;Nuclear;Oncogenes;Oncogenic;Operative Surgical Procedures;Ovarian;Ovarian Carcinoma;ovarian neoplasm;Pancreas;Pathway interactions;Patients;Peritoneal;pharmacologic;Phenotype;Phosphotransferases;poliovirus receptor;prevent;prognostic significance;programmed cell death ligand 1;protein expression;Protein Tyrosine Kinase;PTK2 gene;PTPRC gene;recruit;Recurrence;Resistance;Role;Serous;Signal Transduction;Squamous cell carcinoma;Supporting Cell;System;T-Lymphocyte;Testing;therapy resistant;TNF gene;TP53 gene;transcriptome sequencing;tumor;Tumor Escape;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;Women's mortality

PROJECT_TITLE: Reprogramming the Tumor Microenvironment in Ovarian Cancer

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


NIH_SPENDING_CATS: Attention Deficit Hyperactivity Disorder (ADHD);Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Eye Disease and Disorders of Vision;Mental Health;Neurosciences

ORG_CITY: EAST LANSING

ORG_DEPT: PSYCHOLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE Impairment in attention is associated with many neuropsychological conditions, such as neglect due to stroke, attention deficit-hyperactivity disorder, autism, and Alzheimer’s disease, as well as certain visual problems such as strabismic amblyopia. By elucidating the basic brain mechanisms of attention, the proposed research will inform our understanding of the nature of attentional deficits in these disorders and contribute to the basic research foundation that will ultimately guide the diagnosis and treatment of these disorders.

PI_NAMEs: LIU, TAOSHENG  (contact)

PROGRAM_OFFICER_NAME: WIGGS, CHERI

PROJECT_TERMS: advanced analytics;Affect;Alzheimer's Disease;Anatomy;Architecture;Area;Attention;Attention Deficit Disorder;Attention deficit hyperactivity disorder;Attentional deficit;Auditory;autism spectrum disorder;Automobile Driving;Basic Science;Behavior;Behavioral;Biological Models;Brain;Calibration;Characteristics;Clinical Research;Code;cognitive control;cognitive neuroscience;Computer Models;coping;Data Analytics;Diagnosis;Dimensions;Disease;Dissociation;Dorsal;Environment;feature selection;Foundations;Goals;Health;Human;Impairment;Influentials;information processing;innovation;insight;Learning;Literature;Location;Measures;Mediating;Methodology;Methods;Mission;Modeling;multimodality;Nature;neglect;Nervous System Disorder;neural;neuroimaging;neuromechanism;Neuropsychology;Neurosciences Research;neurotransmission;novel;Perception;Population;Process;Property;Psychophysics;Radiology Specialty;Reading;Research;Research Project Grants;Resolution;response;Role;Scanning;screening;Selection Criteria;selective attention;Signal Transduction;Social Interaction;somatosensory;Stimulus;Stimulus Deprivation-Induced Amblyopia;Stroke;Structure;support network;Techniques;Testing;Theoretical Studies;theories;Time;Variant;Visual;Visual attention;visual information;Visual Perception;visual stimulus;Visual System;Work

PROJECT_TITLE: Representation of attentional priority for visual features in the human brain


ADMINISTERING_IC: AG

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: OKLAHOMA CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: NARRATIVE Aging is the major risk factor for the most economically expensive diseases afflicting the United States today. The Oklahoma Nathan Shock Center will focus on the newly-developing field of Geroscience with Research Cores that deliver unique, innovative services that are accessible to the entire research community studying aging and geroscience. The Research Development Core is designed to provide unprecedented service to the scientific community at large, not just investigators at the host institution.

PI_NAMEs: GALVAN, VERONICA  (contact);VAN REMMEN, HOLLY

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: Address;age effect;age related;age-related disease;Aging;aging related;animal tissue;Award;Bioinformatics;bioinformatics tool;Biological Assay;Biology;Biology of Aging;career;career development;Cell Culture Techniques;Cells;Centers of Research Excellence;Cities;Communities;Country;Couples;Data;Data Analyses;Data Set;design;Development;Disease;DNA;Education;Environment;epigenetic aging;Equipment;Faculty;Foundations;Free Radicals;Funding;Future;Generations;Genes;Genome;genome sciences;genome-wide;Geropathology;Geroscience;Goals;graduate student;Grant;Health Sciences;heteroplasmy;high throughput analysis;Human;Image;In Situ;in vivo;Individual;innovation;Institution;instrumentation;Intervention;Label;large datasets;Mass Spectrum Analysis;Measurement;Measures;Medical center;Medical Research;Mentors;Methods;Methylation;Mitochondria;mitochondrial genome;Modeling;Molecular Target;Mus;Mutation;next generation sequencing;novel;novel strategies;Oklahoma;Organism;outreach;Oxidation-Reduction;oxidative damage;Pathologic;Pathway interactions;Population;Production;programs;Protein Analysis;Protein Biosynthesis;protein degradation;Proteins;Proteomics;Rattus;Reactive Oxygen Species;recruit;Research;research and development;Research Personnel;Resources;Risk Factors;Rodent;Running;Sampling;Services;Shock;Site;Structure;symposium;Techniques;Technology;Tissues;Training;transcriptomics;Travel;United States;Universities;Variant

PROJECT_TITLE: Oklahoma Nathan Shock Center of Excellence in Basic Biology of Aging


NIH_SPENDING_CATS: Aging

PI_NAMEs: SONNTAG, WILLIAM EDMUND (contact)

PROJECT_TERMS: Adopted;age-related disease;Aging;aging related;Applications Grants;Award;Biology of Aging;career;Career Mobility;catalyst;Collaborations;collaborative approach;collaborative environment;Communities;Country;Data Analyses;design;Development;disability;Disease;Education;Ensure;Evaluation;experience;Experimental Designs;Faculty;Foundations;Funding;Funding Agency;Geroscience;Goals;Grant;Health Sciences;Individual;innovation;Institution;interest;Interest Group;investigator training;Laboratories;Medical center;Medical Research;meetings;member;Mentors;new technology;novel;Oklahoma;Outcome;outreach;Performance;Pilot Projects;Productivity;Program Evaluation;programs;Publications;Research;research and development;Research Personnel;Resources;Sampling;Scientist;Senior Scientist;Series;Services;Shock;Strategic vision;Structure;Talents;Technology;Training;United States National Institutes of Health;Universities;web site;Work;Writing

PROJECT_TITLE: Research Development Core


ORG_CITY: AUSTIN

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: Project Narrative This application proposes to establish a new NIA P30 Center on the Demography and Economics of Aging at The University of Texas at Austin (UT Austin)—The Center on Aging and Population Sciences (CAPS). CAPS will promote and support research key to the mission of the NIA P30 program, particularly novel research that illuminates how biosocial and environmental factors intersect, compound, and cascade throughout the life course to shape health and well-being at older ages. CAPS research will offer new insights critical to furthering the health and well-being of a diverse aging US population.

PI_NAMEs: UMBERSON, DEBRA J. (contact)

PROGRAM_OFFICER_NAME: BANDIERA, FRANK

PROJECT_TERMS: Address;Administrator;Affect;African American population;Age;Aging;Area;arm;Biological Process;Biosocial;Birth;career;Center Core Grants;Childhood;Collaborations;Communication;Communities;Complex;Data;Demographer;Demography;design;Development;Dimensions;Disadvantaged;Discipline;Disparity;Disparity population;Economics;Ensure;Environmental Risk Factor;ethnic minority status;Ethnic Origin;Evolution;experience;Extramural Activities;Faculty;Family Demographies;family structure;Fostering;Foundations;Funding;Geographic Locations;Health;health disparity;health inequalities;Hispanic Populations;human old age (65+);improved;Infrastructure;infrastructure development;innovation;insight;Institution;Knowledge;late life;Leadership;Life;Life Cycle Stages;Mission;Neighborhoods;novel;older adult;Outcome;Personal Satisfaction;Persons;Pilot Projects;Population;Population Dynamics;population health;Population Research;Population Sciences;Productivity;Program Development;programs;Race;racial minority status;Research;Research Personnel;Research Support;Resources;Role;Scientist;Services;Sexual and Gender Minorities;sexual minority status;Shapes;social engagement;Social isolation;Social Processes;Socioeconomic Status;socioeconomics;Source;Texas;Time;Universities;Work

PROJECT_TITLE: Center on Aging and Population Sciences


PI_NAMEs: GALVAN, VERONICA  (contact)

PROJECT_TITLE: Program Enhancement Core


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

PHR: Project Narrative As stated in RFA-AG-20-001 the project narrative is not to be completed for this component.

PROJECT_TERMS: Administrator;Advisory Committees;Aging;Applications Grants;Attention;Award;Biosocial;Center Core Grants;Collaborations;Communication;Communities;Consult;Demography;design;Development;Economics;Educational workshop;Environmental Risk Factor;Event;experience;Faculty;Fostering;Funding;Future;Goals;Grant;Health;human old age (65+);Infrastructure;Institution;Leadership;Life;Life Cycle Stages;Logistics;meeting reports;Mission;Monitor;National Institute of Child Health and Human Development;novel;operation;Outcome;Personal Satisfaction;Phase;Pilot Projects;Population;Population Research;Population Sciences;Procedures;Productivity;Program Development;programs;Publications;Ramp;Research;Research Project Grants;Research Support;Resource Sharing;Resources;scale up;Scientist;Series;Services;Shapes;Strategic vision;success;symposium;Time;Universities;Work

PROJECT_TITLE: Administrative and Research Support Core


PI_NAMEs: FREEMAN, WILLARD M (contact)

PROJECT_TERMS: age related changes;Aging;aging mechanism;anti aging;Applications Grants;Area;base;Bioinformatics;Biology of Aging;bisulfite;Cell Aging;Cell Separation;cell type;Cells;Chromium;Core Facility;cost;Country;CpG Islands;Cytosine;Data;Data Analyses;design;digital;DNA;DNA analysis;DNA Damage;DNA Modification Process;Epigenetic Process;epigenome;epigenomics;Functional disorder;Funding;Generations;Genes;Genetic Transcription;Genome;genome sciences;genome-wide;genome-wide analysis;Genomic Segment;Genomics;Geroscience;Goals;Heart;Heterogeneity;heteroplasmy;Human Genome;human genome sequencing;Individual;Institution;instrumentation;Intervention;Laboratories;Letters;Measures;meetings;Methods;Methylation;Mitochondria;Mitochondrial DNA;mitochondrial DNA mutation;mitochondrial dysfunction;mitochondrial genome;model organism;Modernization;Molecular Biology;mouse genome;Mus;next generation sequencing;Nucleic Acid Regulatory Sequences;Nucleic Acids;Oklahoma;Oligonucleotides;prevent;promoter;Proteomics;Provider;rat genome;Rattus;Research;Research Personnel;Resolution;Resources;Sampling;Services;Shock;single-cell RNA sequencing;Speed;targeted sequencing;Technology;Tissue Sample;Tissues;tool;transcriptome;transcriptome sequencing;transcriptomics;usability;Variant;whole genome

PROJECT_TITLE: Genomic Sciences Core


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Social Determinants of Health

PI_NAMEs: FINGERMAN, KAREN L (contact)

PROJECT_TERMS: Address;Aging;Area;Benchmarking;Biosocial;Caliber;career;Charge;Collaborations;Communities;Data;Data Sources;Development;Disadvantaged;Educational workshop;Ensure;Environmental Risk Factor;experience;faculty mentor;Family Demographies;Fostering;Funding;Goals;Grant;Health;high reward;high risk;human old age (65+);Incubated;Infrastructure;innovation;insight;Institution;interdisciplinary collaboration;International;Investments;Life;Life Cycle Stages;Mentors;Methods;Mission;Monitor;Nature;novel;Personal Satisfaction;Pilot Projects;Population;population based;Population Research;Population Sciences;Preparation;Productivity;Program Development;programs;Publications;Qualifying;Ramp;Research;Research Personnel;Research Priority;Research Project Grants;Research Support;Resource Sharing;response;Running;Scholarship;Science;Scientist;Services;Shapes;social engagement;Social isolation;success;symposium;Time;Training;Work;Writing

PROJECT_TITLE: Program Development and Pilot Core


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

ORG_CITY: OMAHA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Project Narrative:  Mechanisms underlying the initiation and persistence of lethal cardiac rhythms are of significant clinical interest. Changes in connexin distribution, density, and/or properties are characteristic of arrhythmic heart disease; therefore, understanding what causes alterations in gap junction properties in heart disease is essential for defining the pathological substrate and devising effective therapies. The rationale for the proposed basic science research is that understanding the mechanistic basis of Cx43 and Cx45 regulation will lead to possible points of therapeutic intervention to restore proper gap junction intercellular communication that has been altered due to heart failure.

PI_NAMEs: SORGEN, PAUL L (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Acute;Affect;Arrhythmia;Basic Science;beta Tubulin;Binding;Cardiac;Cells;Characteristics;Chronic;Clinical;Connexin 43;Connexins;Coupling;cytokine;Cytoplasm;Data;density;Development;Disease;Distal;drebrins;effective therapy;experimental study;F-Actin;gap junction channel;Gap Junctions;Growth;Growth Factor;Heart;Heart Diseases;Heart failure;heart rhythm;human disease;Hypertrophy;In Vitro;Infarction;insight;Integral Membrane Protein;Intercalated disc;intercellular communication;interdisciplinary approach;interest;intermolecular interaction;Ion Exchange;Ischemia;Knowledge;Lateral;Left ventricular structure;Link;Mediating;Membrane;molecular mass;Morphology;mouse model;Muscle Cells;Myocardial dysfunction;Myocardial Infarction;Myocardium;novel;Pathologic;Pathology;Pathway interactions;Permeability;Phosphorylation;Phosphotransferases;prevent;Process;Property;Proteins;Regulation;Research;Role;Signal Transduction;Signaling Molecule;SRC gene;Testing;Therapeutic;Therapeutic Intervention;Tubulin;Up-Regulation;Ventricular;Ventricular Arrhythmia;voltage

PROJECT_TITLE: Mechanisms of Gap Junction Regulation

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative:  T cells and immune suppressive regulatory T (Treg) cells are pivotal in immune homeostasis and diseases. It is critical to understand the functional protein networks underlying T and Treg cell function. Our recent study revealed an unexpected critical role for innate senor AIM2 (Absent In Melanoma 2) in controlling Treg cell function to mitigate autoimmune EAE, by modulating Akt-mTOR signaling. Based on these exciting findings, we propose to study how the expression and function of AIM2 in Treg cells are controlled through mechanisms both distinct from and shared with those found in the innate cells, to uphold tolerance and restrain autoimmunity. This study will highlight a previously unappreciated critical role for AIM2, shed new lights on the molecular networks underlying Treg cell function, and reveal potential novel molecular targets and therapies for autoimmune diseases.

PI_NAMEs: WAN, YISONG  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: adaptive immune response;adaptive immunity;Address;AIM2 gene;Attenuated;Autoimmune;Autoimmune Diseases;Autoimmunity;Binding;Binding Proteins;Biochemical;CASP1 gene;CD4 Positive T Lymphocytes;cell growth;Cell Physiology;Cells;Cellular biology;Cues;Disease;disease model;DNA Integration;ds-DNA;Ensure;Experimental Autoimmune Encephalomyelitis;FOXP3 gene;FRAP1 gene;Funding;Generations;Genetic;Health;histone modification;Homeostasis;Human;Immune;immune activation;immune function;Immune response;immune system function;Immunologics;Immunosuppression;Immunosuppressive Agents;In Vitro;in vivo;Infection;Inflammasome;Inflammation;Inflammatory;Innate Immune Response;insight;Investigation;Laboratories;Malignant Neoplasms;Maps;Mediating;Metabolism;Molecular;Molecular Target;multiple omics;Mus;novel;Pathway interactions;Progress Reports;Proliferating;Protein Phosphatase 2A Regulatory Subunit PR53;Proteins;Publications;Regulatory T-Lymphocyte;Research;Resistance;restraint;Role;Self Tolerance;sensor;Signal Transduction;SKI gene;Suppressor-Effector T-Lymphocytes;T-Lymphocyte;Testing;Transforming Growth Factor beta

PROJECT_TITLE: Functional protein networks underlying T cell growth, proliferation and differentiation

STUDY_SECTION: CMIB

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


ORG_CITY: NEW HAVEN

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative The proposed research is relevant to public health because it aims to define a critical mechanism for signal transduction that leads to immune responses against pathogen infection and cancer progression. Thus, this work is in line with NIGMS’s mission in supporting basic research that increases the understanding of biological processes and lay the foundation for disease treatment.

PI_NAMEs: SU, XIAOLEI  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Address;Affect;Antigens;Basic Science;Biological Process;cell killing;Cell membrane;Cell Nucleus;Cells;Charge;Cytoplasm;Disease;Environment;extracellular;Foundations;Geometry;Goals;Immune response;Infection;Inner Leaflet of the Lipid Bilayer;Lipid Bilayers;Lipids;Mediating;Membrane;Mission;National Institute of General Medical Sciences;pathogen;Pathway interactions;Phase;Physical condensation;Process;protein protein interaction;Proteins;Public Health;Receptor Activation;Receptor Signaling;Research;self assembly;Signal Transduction;Signaling Molecule;Stimulus;System;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;three dimensional structure;tumor progression;Work

PROJECT_TITLE: Spatial Organization of Membrane Signaling

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


PI_NAMEs: KINTER, MICHAEL T (contact)

PROJECT_TERMS: Acetylation;Affinity;age-related disease;Aging;aging related;Animals;Biochemical Pathway;Biogenesis;Biological Assay;Biology;Biology of Aging;Caenorhabditis elegans;Cell Proliferation;cell type;Cells;Citric Acid Cycle;Communities;Complex;Consult;Core Facility;Data Analyses;design;Deuterium;Deuterium Oxide;Development;Dissociation;DNA;DNA biosynthesis;Drosophila genus;experience;experimental study;flexibility;Freezing;Funding;Genome;Geroscience;Gluconeogenesis;Glycolysis;Goals;Half-Life;Immobilization;Individual;insight;instrument;interest;Ions;Kinetics;Label;Laboratories;Mass Fragmentography;Mass Spectrum Analysis;Measurement;Measures;Metals;Methods;model organism;Modeling;Modification;Molecular;Monitor;Mus;Nucleotides;Oklahoma;Peptides;Phosphorylation;Post-Translational Protein Processing;Preparation;Procedures;Process;Protein Analysis;Protein Biosynthesis;protein degradation;Proteins;Proteome;Proteomics;proteostasis;Rattus;Reaction;Regulation;Research;Research Design;Research Personnel;Resolution;Resources;Ribosomes;RNA;RNA chemical synthesis;Running;sample collection;Sampling;selected ion monitoring;Services;Shock;stable isotope;Stable Isotope Labeling;System;tandem mass spectrometry;Tissues;tool;Tracer;Trypsin;ultra high resolution;Western Blotting;Yeasts

PROJECT_TITLE: Multiplexing Protein Analysis Core


NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Data Science;Genetics;Human Genome;Networking and Information Technology R&D (NITRD)

PI_NAMEs: WREN, JONATHAN DANIEL (contact)

PROJECT_TERMS: Acarbose;Age;age effect;age related;age related changes;aged;Aging;aging related;Area;ATAC-seq;Autophagocytosis;Big Data;Binding Sites;Bioinformatics;Biological;Biology;Biology of Aging;bisulfite sequencing;Caloric Restriction;Categories;Cell Culture Techniques;cell type;Cells;Chemicals;ChIP-seq;Cities;Communities;Computer software;Custom;Data;Data Analyses;Data Set;Data Sources;Databases;design;Development;Disadvantaged;Disease;Estradiol;experience;experimental analysis;Experimental Designs;experimental study;Frequencies;Genes;Genetic Transcription;Genome;genome annotation;genome sciences;Genomic Segment;Genomics;Geroscience;Goals;Grouping;Guilt;high throughput analysis;Human;Human Resources;Individual;infancy;Informatics;innovation;Institution;interest;Intervention;Laboratories;large datasets;large scale data;Literature;Longevity;metabolomics;method development;Methods;Methylation;Molecular;Molecular Analysis;Molecular Biology;novel;Oklahoma;Ontology;Pathway interactions;Phenotype;Process;programs;Proteomics;proteostasis;Publications;Publishing;Research Personnel;response;Resveratrol;Sampling;Science;senescence associated secretory phenotype;senescent cell;Services;Shock;single cell sequencing;single-cell RNA sequencing;Sirolimus;software development;software infrastructure;Software Tools;Statistical Data Interpretation;statistics;stem cells;Technology;Testing;Tissues;transcription factor;transcriptome;transcriptome sequencing;transcriptomics;Troglodytinae;Untranslated RNA;Validation;Visual

PROJECT_TITLE: GeroInformatics Core


NIH_SPENDING_CATS: Behavioral and Social Science;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Hematology;Immunotherapy;Networking and Information Technology R&D (NITRD);Orphan Drug;Patient Safety;Pediatric;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE This Midcareer Investigator K24 Award in Patient-Oriented Research will provide the candidate, Sung Won Choi MD MS, protected time to act as a research mentor for early stage investigators conducting patient-oriented research. Dr. Choi has devoted her career to improving the clinical and health-related quality of life outcomes (HRQOL) of family caregivers and patients undergoing hematopoietic cell transplantation (HCT) by: i) designing and executing rigorous clinical trials; ii) incorporating innovative correlative studies; and iii) leveraging mobile health technologies to enhance care delivery. Thus, her research program offers a rich training environment for early stage investigators to pursue patient-oriented research in HCT.

PI_NAMEs: CHOI, SUNG WON  (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: acceptability and feasibility;Active Learning;Acute Graft Versus Host Disease;adaptive intervention;Address;Adolescent and Young Adult;Adult;Affect;Allogenic;Applications Grants;Area;Attitude;Behavioral;Biological;Biological Process;Biological Products;Blood specimen;Cardiovascular Diseases;care delivery;career;Caregivers;Caring;Child;Childhood;Clinical;Clinical and Translational Science Awards;Clinical Investigator;Clinical Trials;Clinical Trials Design;Clinical Trials Support Unit;cognitive testing;Collection;Communication;Correlative Study;Coupled;Data;Data Analytics;Data Collection;Data Science;design;Development;Development Plans;Diabetes Mellitus;Dose;Drug Kinetics;early phase clinical trial;early phase trial;effective therapy;effectiveness evaluation;Electronic Health Record;Environment;Ethics;experience;Family Caregiver;Frequencies;Functional disorder;Funding;Future;global health;Goals;graft vs host disease;Grant;Growth;HDAC4 gene;Health;health care service utilization;health related quality of life;Health Technology;Healthcare;Hematological Disease;Hematology;Hematopoietic Stem Cell Transplantation;high risk;Histone Deacetylase Inhibitor;human disease;human subject protection;Immunotherapy;improved;Individual;Infrastructure;innovation;insight;interest;Intervention;intervention delivery;Interview;Knowledge;Life;Manuscripts;Measures;Mental disorders;Mental Health;Mentors;mHealth;Michigan;Mid-Career Clinical Scientist Award (K24);Mobile Health Application;Modernization;Morbidity - disease rate;mortality;multidisciplinary;National Heart, Lung, and Blood Institute;Neurocognitive;next generation;novel;novel therapeutics;Outcome;Participant;patient oriented research;Patient Self-Report;Patients;Pediatric Oncologist;Pharmacodynamics;Pharmacologic Substance;Phase I/II Clinical Trial;physical conditioning;Physicians;Physiological;Population;post-transplant;prevent;prevention clinical trial;Prevention strategy;primary outcome;programs;Prophylactic treatment;Psychology;psychosocial;Public Health Schools;Randomized;randomized trial;Randomized, Controlled Trials;Research;Research Methodology;Research Personnel;Research Project Grants;research study;Resources;Safety;safety testing;Science;Scientist;secondary outcome;skills;smoking cessation;social;Solid;Technology;Testing;Time;tool;Training;training opportunity;Transplant Recipients;trend;trial design;United States National Institutes of Health;Universities;Vorinostat;wearable data;wearable sensor technology;Writing

PROJECT_TITLE: Patient-Oriented Research and Mentoring in Hematopoietic Cell Transplantation

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(JA)]


NIH_SPENDING_CATS: Aging;Biomedical Imaging

PI_NAMEs: VAN REMMEN, HOLLY  (contact)

PROJECT_TERMS: Age;age-related disease;Aging;aging mechanism;aging related;Bioenergetics;Biological;Biological Assay;Biology;Biology of Aging;Blood Vessels;Cell Culture Techniques;cell injury;Cell Respiration;Cells;Cellular Structures;Charge;Communities;cost;Couples;Deoxyguanosine;Diabetes Mellitus;Diffusion Magnetic Resonance Imaging;Disease;DNA;energy balance;Environment;Equilibrium;Equipment;Evaluation;Excision;extracellular;F2-Isoprostanes;Free Radicals;Freezing;Fresh Tissue;Functional Magnetic Resonance Imaging;Generations;Genus Hippocampus;Geroscience;Glutathione Disulfide;Goals;Homeostasis;Human;Hydrogen;In Vitro;in vivo;in vivo evaluation;in vivo imaging;Individual;insight;Institution;Invertebrates;Laboratories;Lipid Peroxidation;Lipids;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Malignant Neoplasms;Measurement;Measures;Metabolism;Mitochondria;Modeling;Molecular;Mus;NADH;NADP;Nature;Neurodegenerative Disorders;Oklahoma;Organism;Oxidants;oxidation;Oxidation-Reduction;oxidative damage;Oxidative Stress;Oxygen;Pathway interactions;perfusion imaging;Permeability;Phosphorus;Physiological Processes;prevent;Process;Production;Proteins;Reaction;Reactive Oxygen Species;Reproducibility;Research;Research Personnel;Respiration;Rodent;Sampling;Sensitivity and Specificity;Series;Services;Shock;Site;Spin Trapping;Spirometry;System;Technology;Tissues;Vascular Diseases

PROJECT_TITLE: Geroscience Redox Biology Core


NIH_SPENDING_CATS: Bioengineering;Genetics;Human Genome

PHR: Project Narrative The proposed research program seeks to understand how genomic information is organized and accessed by direct observation across scales—from single molecules to mesoscale reactions toward behaviors in living nuclei. The organization and structure of chromatin in the cell of often dictates when and how DNA sequences are processed and perturbing chromatin architecture can lead to misregulation of genes, errors in differentiation and development, and genome instability, all of which lead to a host of maladies in living organisms. By connecting newly accessible in vivo measurements into mechanistic frameworks of individual protein actions, many long-standing problems in chromatin biology are likely to be resolved.

PI_NAMEs: REDDING, SY  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: 3-Dimensional;Architecture;Behavior;Biological Assay;Biology;biophysical properties;Cell Nucleus;Cells;Chromatin;Chromatin Fiber;Chromatin Structure;Crowding;Development;Dimensions;Disease;DNA;DNA Sequence;Environment;Epigenetic Process;experimental study;Free Energy;Genes;genetic information;Genome;Genomic Instability;Genomics;Imaging Device;In Vitro;in vivo;Individual;Investigation;laser tweezer;Measurement;Measures;Modeling;novel;optic tweezer;Organism;Partition Coefficient;Physical condensation;Play;Process;programs;Proteins;Reaction;Regulation;Research;Resolution;Role;single molecule;Structure;Testing;Tube;Work

PROJECT_TITLE: Physical determinants of DNA recognition and genome organization in crowded environments

STUDY_SECTION: MRAA

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


NIH_SPENDING_CATS: Brain Disorders;Cancer;Congenital Structural Anomalies;Genetics;Hematology;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative The project proposed in this application seeks to understand the pathogenic effects of the aberrant bone marrow microenvironment on resident blood forming stem cells in Noonan syndrome (NS), a developmental disorder that has an increased risk of developing leukemia. This work will establish a framework for the rational design of new therapeutics, which may ultimately lead to improvements in prevention of leukemia development in NS and in stem cell transplantation therapy for NS-associated leukemia.

PI_NAMEs: QU, CHENG-KUI  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Adrenergic Receptor;Bone Marrow;Bone Marrow Cells;Bone Marrow Neoplasms;Cell surface;cell type;Cells;chemokine;Clinical Management;congenital heart abnormality;cytokine;Data;Development;developmental disease;Disease;Embryonic Development;Face;Funding;gain of function;Genes;Germ Lines;Germ-Line Mutation;Hematologic Neoplasms;Hematopoietic;Hematopoietic stem cells;Heterozygote;Hormones;Human;improved;In Vitro;Juvenile Myelomonocytic Leukemia;Knock-in Mouse;Knowledge;Laboratories;leukemia;leukemogenesis;Maintenance;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Mental Retardation;Mesenchymal Stem Cells;Molecular;mouse model;Mus;mutant;Mutate;Mutation;Myeloproliferative disease;Nerve Fibers;nestin protein;Neural Crest;Neuroglia;Neurotransmitters;Noonan Syndrome;novel;novel therapeutic intervention;novel therapeutics;Osteoblasts;osteoprogenitor cell;Pathogenesis;Pathogenicity;Patients;Peripheral Nervous System;prevent;Prevention;Prognosis;protein protein interaction;Protein Secretion;Protein Tyrosine Phosphatase;Proteins;PTPN11 gene;Ras Signaling Pathway;rational design;Receptor Signaling;Research;Risk;Role;Schwann Cells;Signal Pathway;Signaling Molecule;Specimen;Stem cell transplant;stem cells;Structure;Testing;therapeutic development;Therapeutic Intervention;trafficking;Transplantation;transplantation therapy;Treatment outcome;Work

PROJECT_TITLE: Germline mutations of PTPN11 (SHP2) in the stem cell microenvironment

STUDY_SECTION: MCH

STUDY_SECTION_NAME: Molecular and Cellular Hematology Study Section[MCH]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

ORG_DEPT: PSYCHIATRY

PHR: HEALTH RELEVANCE NARRATIVE Neuroactive steroids (NAS) represent an innovative direction in psychiatric therapeutics. Our Conte Center will unite a group of scientists with internationally-recognized expertise in the chemistry and biology of NAS to understand mechanisms underlying the psychotropic effects of NAS, focusing on ion channel, synaptic, neural circuitry and behavioral effects of novel NAS. These studies have the potential to lead to new treatments for psychiatric illnesses.

PI_NAMEs: MENNERICK, STEVEN J (contact);ZORUMSKI, CHARLES F

PROGRAM_OFFICER_NAME: NADLER, LAURIE SUE

PROJECT_TERMS: Allopregnanolone;analog;anti-depressive agents;antidepressant effect;Behavior;Behavioral;Biological;Biology;Brain;Calcium Channel;Catalogs;Cause of Death;Cell Physiology;cell type;Cellular Stress;Chemistry;Collaborations;Complement;Data;Development;disability;Disease;drug development;Enhancers;experience;FDA approved;Formulation;Fostering;Funding;Future;GABA Agents;gamma-Aminobutyric Acid;Glutamate Receptor;Goals;Health;Hippocampus;improved;Inflammation;Inflammatory;innovation;insight;International;Ion Channel;Ketamine;Ligands;Major Depressive Disorder;Mass Spectrum Analysis;Mediating;Medical;member;men;Mental disorders;Modernization;Molecular;Molecular Target;mouse model;multidisciplinary;Mus;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;neural circuit;neural network;neuroinflammation;Neurons;neurosteroids;novel;novel therapeutics;Oral;Pathway interactions;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Phase;phase 3 study;Photoaffinity Labels;Positioning Attribute;Postpartum Depression;Postpartum Period;Productivity;programs;prototype;Psychiatric therapeutic procedure;receptor;Recording of previous events;Research;Research Personnel;Research Support;Resources;Role;Scientist;Seminal;side effect;Site;steroid analog;Steroids;Stress;Structure;success;Synapses;Testing;Therapeutic;therapeutic development;Therapeutic Effect;tool;Translational Research;voltage;Woman;women's treatment;Work

PROJECT_TITLE: Neuroactive steroids as novel psychiatric treatments: mechanistic studies


ADMINISTERING_IC: HD

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

ORG_CITY: BOSTON

ORG_DEPT: GENETICS

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE Defects in gut formation lead to serious birth defects. This study will shed light on how the digestive tract attains its proper shap and structure, allowing it to perform its key functions in absorbing nutrients.

PI_NAMEs: TABIN, CLIFFORD J. (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Address;Agonist;Anatomy;antagonist;Architecture;Biochemical;biophysical properties;Biophysics;Characteristics;Chick;Chick Embryo;Computer Models;Congenital Abnormality;Defect;Development;Dimensions;Disparate;Embryonic Development;Environment;Epithelium;Equilibrium;Erinaceidae;Esophagus;Event;experience;Experimental Models;experimental study;Family;Fiber;Fingers;Gastrocoele;Gastrointestinal tract structure;Gene Expression Profiling;Generations;Genes;Genetic;Genetic Transcription;Growth;Hindgut;In Situ Hybridization;in vivo;insight;intestinal villi;Large Intestine;Lead;Link;Location;mathematical model;Measures;mechanical force;Mechanics;Mesenchyme;Mesoderm;Microdissection;Midgut;Molecular;Morphogenesis;morphogens;Morphology;Mucous Membrane;Muscle;Muscle Fibers;nutrient absorption;Organ;Pathway interactions;Pattern;Pharmaceutical Preparations;Play;Primitive foregut structure;programs;Property;Radial;Retroviral Vector;Role;Series;Shapes;Signal Transduction;Small Intestines;Smooth Muscle;Specific qualifier value;Stress;Structure;Surface;System;Testing;Thick;Time;Tissue Recombination;Tissues;transcription factor;transcription factor USF;Tube;Undifferentiated;Variant;Villus;Work

PROJECT_TITLE: Signals and mechanical forces controlling radial gut morphogenesis

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


NIH_SPENDING_CATS: Mental Health;Neurosciences

PHR: ADMINISTRATIVE CORE – PROJECT NARRATIVE The Administrative Core will coordinate and support all the Projects and Cores, facilitate outreach through a website and social media, and will coordinate training efforts of the Center.

PI_NAMEs: MENNERICK, STEVEN J (contact)

PROJECT_TERMS: Administrator;Award;Budgets;Chemicals;Chemistry;Colorado;Communication;Communities;Education and Outreach;Educational Activities;Equipment and supply inventories;Event;Facebook;Faculty;Festival;Human Resources;Infrastructure;Institution;Knowledge;Link;medical schools;meetings;member;Monitor;Mus;neurosteroids;news;novel;outreach;Postdoctoral Fellow;Psychiatric therapeutic procedure;Public Relations;Publications;Reagent;Research Activity;Research Support;Resource Sharing;Resources;Schools;Science;science museum;Site;social media;Students;symposium;Taste Perception;tool;Training;Travel;Twitter;Universities;Viral Vector;Washington;web site;Work

PROJECT_TITLE: Administration Core


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Aging;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Patient Safety;Physical Injury - Accidents and Adverse Effects;Prevention;Racial and Ethnic Minority Health Research;Wound Healing and Care

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Public Health Relevance/Project Narrative Pressure injuries, local areas of damage to the skin and underlying soft tissue that are costly and painful, are often preventable if repeated instances of mechanical forces can be lessened with timely implementation of prevention strategies. Identification of early pressure induced tissue damage among nursing home residents by nursing staff during routine skin assessment is critical because detection cues initiation of prevention actions and may allow viable tissue rescue, lessening morbidity and mortality. We propose use of sub-epidermal moisture (SEM) measures as the cue for initiating pressure injury prevention because it offers significant promise by: 1) providing early detection of PrI damage by as much as 5 to 10 days prior to any visual skin discoloration, which can trigger prompt, effective, individualized prevention, 2) eliminating the inherent structural bias in visual skin assessment for residents with dark skin tones, 3) demonstrating a model of care using technology innovation in poorly-resourced healthcare settings, and 4) providing bedside, real-time, point- of-care feedback that is immediately actionable by nursing staff, the daily care providers for frail, vulnerable elders.

PI_NAMEs: BATES-JENSEN, BARBARA M. (contact);YAP, TRACEY

PROGRAM_OFFICER_NAME: HUSS, KAREN

PROJECT_TERMS: acute care;Admission activity;Adoption;Age;Area;biophysical techniques;Biophysics;Black race;Body mass index;care providers;Caring;Characteristics;Clinical;Clinical assessments;Clinical Practice Guideline;Clinical Trials;Clinical Trials Design;Cognitive;cost;Coupled;Cues;Dangerousness;Darkness;Data;decubitus ulcer;Dermal;design;Detection;detection method;Development;Devices;Discipline of Nursing;Disparity;Early Diagnosis;Early identification;Edema;Effectiveness;Elderly;Electric Capacitance;Electronic Health Record;Erythema;ethnic health disparity;Ethnic Origin;Ethnic Population;Feedback;Focus Groups;Future;Gender;Goals;Guidelines;healing;health care settings;health disparity;Health Resources;Heel;hospital care;Hospitals;Incidence;Individual;individualized prevention;Inflammation;Injury;injury prevention;innovation;Intention;International;Intervention;Knowledge;Long-Term Care Nursing;Measurement;Measures;mechanical force;medical specialties;Mental Depression;Methods;Minority;Modeling;Morbidity - disease rate;mortality;Muscle;Nursing Homes;Nursing Staff;Pain;Periodicals;Persons;point of care;Policies;pressure;Prevalence;prevent;Prevention;Prevention Guidelines;prevention practice;Prevention Protocols;Prevention strategy;Preventive;Procedures;public health relevance;Quality of life;Race;racial health disparity;racial population;Resources;Risk;Risk Assessment;Safety;Sampling;Science;Severities;Skin;skin damage;skin discoloration;soft tissue;standard of care;Standardization;Surface;technological innovation;Technology;Testing;Time;Tissue Viability;Tissues;usability;Visual;Visualization

PROJECT_TITLE: Biophysical detection of skin changes to cue pressure injury prevention in nursing homes

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


NIH_SPENDING_CATS: Brain Disorders;Depression;Mental Health;Mental Illness;Neurosciences

ORG_NAME: WASHINGTON UNIVERSITY

PHR: Project Narrative Neurosteroids are rapidly acting anti-depressant agents with an undefined mechanism of action. The proposed research will identify specific neurosteroid binding sites on putative target proteins as well as novel neurosteroid binding proteins, enabling assessment of the functional role of these target proteins in anti-depressant physiology and behavior. The work will provide the basis for synthesizing compounds that target the specific proteins and sites that mediate neurosteroid anti-depressant effects, leading to novel therapeutics and insights into the biology of naturally occurring neurosteroids.

PI_NAMEs: EVERS, ALEX S. (contact)

PROJECT_TERMS: Affinity;Agonist;Alkynes;Allopregnanolone;Amino Acids;analog;Anesthetics;antagonist;Anti-Anxiety Agents;anti-depressive agents;anti-epileptic agents;Anti-Inflammatory Agents;antidepressant effect;Automobile Driving;Autophagocytosis;Behavior;Behavior assessment;Behavioral;beta Tubulin;Binding;Binding Proteins;Binding Sites;Biological;biological adaptation to stress;Biological Assay;Biology;Brain;Carrier Proteins;Cell membrane;Cellular Stress;Chemicals;Chemistry;Cholesterol;Clustered Regularly Interspaced Short Palindromic Repeats;Coupled;Data;Development;Docking;Electrophysiology (science);enantiomer;Goals;Golgi Apparatus;Hippocampus;in vivo;Inflammatory;insight;Intracellular Membranes;Ion Channel;Ketamine;Knock-out;Label;Link;lipid transfer protein;lipid transport;Lipids;liquid chromatography mass spectrometry;Maps;Mass Spectrum Analysis;Mediating;Membrane;Mental Depression;Methods;Molecular;molecular modeling;Molecular Target;Mutation;N-Methyl-D-Aspartate Receptors;network dysfunction;neuroinflammation;neuronal excitability;Neurons;neurosteroids;Nitrous Oxide;NMDA receptor A1;novel;novel therapeutics;Organelles;Output;oxysterol binding protein;Pathway interactions;Phospholipids;Photoaffinity Labels;Physiological;Physiological Processes;Physiology;positive allosteric modulator;Protein Chemistry;protein expression;Protein Isoforms;Proteins;Proteome;Proteomics;Psychiatric therapeutic procedure;Reagent;receptor;Receptor Inhibition;Research;Research Support;response;Role;sedative;Signal Transduction;Site;steroid analog;Sterols;Techniques;Therapeutic;trans-Golgi Network;Treatment Efficacy;Work

PROJECT_TITLE: Molecular Targets of Neurosteroid Anti-depressant Action


ORG_DEPT: SURGERY

PHR: Project Narrative It is poorly understood how T cells are affected by tumor metabolism in the tumor microenvironment. We will explore the molecular mechanisms of effector T cell survival and functional potency, amino acid circuits in T cells, and the methionine metabolism-associated immune alteration. The proposal will provide an opportunity to take our understanding of effector T cell biology in the tumor to a new level of mechanism and application.

PI_NAMEs: ZOU, WEIPING  (contact)

PROJECT_TERMS: Address;Affect;amino acid metabolism;Amino Acids;Apoptosis;Avidity;cancer therapy;cancer type;cancer vaccination;Cancer Vaccines;Carbon;CD8-Positive T-Lymphocytes;Cell Physiology;Cell Survival;Cells;Cellular biology;chimeric antigen receptor T cells;Clinical;Clinical Research;Colon Carcinoma;combinatorial;cytotoxic;Data;design;effector T cell;Epigenetic Process;exhaust;Family member;Functional disorder;Genes;Genetic Transcription;Glycolysis;Goals;Histones;Human;Immune;immune checkpoint blockade;Immune Evasion;Immunity;Immunotherapeutic agent;Immunotherapy;Impairment;Knowledge;Link;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Metabolic;Metabolism;Methionine;Methionine Metabolism Pathway;Methylation;Molecular;Mus;Nature;neoantigens;neoplasm immunotherapy;neoplastic cell;novel;Oncogenic;Oxidative Stress;Patients;Pattern;PD-1 blockade;PD-1/PD-L1;Phenotype;practical application;Predisposition;Property;Regimen;Research;response;Role;S-Adenosylhomocysteine;S-Adenosylmethionine;Signal Pathway;Signal Transduction;solute;Stat5 protein;T memory cell;T-Lymphocyte;Testing;Therapeutic;Treatment Efficacy;tumor;Tumor Immunity;tumor immunology;tumor metabolism;tumor microenvironment;Vaccination;Warburg Effect

PROJECT_TITLE: Metabolic impact on T cell-mediated cancer immunity and therapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ORG_CITY: AUGUSTA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: AUGUSTA UNIVERSITY

PHR: Project Narrative Movement disorders are a collection of neurological disorders that lead to abnormal motor control, which results in a considerable public health concern. The studies in this proposal will investigate neuronal signaling processes that play an essential role in motor function. A better understanding of the mechanisms that modulate information transfer between neurons is expected to have practical implications for targeted therapy in movement disorder patients.

PI_NAMEs: MUNTEAN, BRIAN S (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Acute;adenylyl cyclase type V;Binding;Biochemical;Biological Assay;Brain;Caring;Cells;Clinical;Collection;Complex;conditional knockout;Corpus striatum structure;Coupled;CRISPR/Cas technology;Cyclic AMP;Data;Deep Brain Stimulation;Development;Disease Progression;disease-causing mutation;Dyskinetic syndrome;Dystonia;Environment;Enzymes;Etiology;Event;Feedback;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Genes;Genetic;Genetic Markers;Goals;GTP-Binding Proteins;Image;Impairment;insight;Investigation;Knockout Mice;Logistics;Molecular;Motor;motor control;mouse model;Movement Disorders;Mutation;Nervous System Disorder;Neurons;neuroregulation;neurotransmission;optical sensor;Optics;Pathogenicity;Pathway interactions;Patient-Focused Outcomes;Patients;Physiological;Physiology;Play;Positioning Attribute;postsynaptic;Potassium Channel;pressure;Prevalence;Process;Protein Family;Proteins;Public Health;receptor;Regulation;Research;Role;sensor;Shapes;Signal Transduction;Signaling Protein;Slice;targeted treatment;Testing;Therapeutic;therapeutically effective;Tissues;Transducers;two-photon;Variant;Work;Zinc;zinc-binding protein

PROJECT_TITLE: Role of KCTD proteins in striatal signaling

STUDY_SECTION: MCNP

STUDY_SECTION_NAME:
Molecular and Cellular Neuropharmacology Study Section
[MCNP]


ORG_CITY: SAINT LOUIS

PHR: Project Narrative The mechansims by which neurosteroids provide antidepressant benefit are unclear. These studies represent a comprehensive evaluation of various structural analogues of an antidepressant neurosteroid to identify new understand cellular mechanisms by which neurosteroids alter neuronal function, thereby identifying new drug candidates.

PROJECT_TERMS: Acute;Allopregnanolone;Amygdaloid structure;analog;antagonist;anti-depressive agents;Automobile Driving;Autophagocytosis;Behavior;Behavioral;Binding Sites;Biological Assay;Brain;Calcium Channel;Cell membrane;Cells;Cellular Stress;cellular targeting;Characteristics;Chemicals;Clinical;cytokine;Data;Development;drug candidate;enantiomer;Engineering;Evaluation;Evolution;Exhibits;Frequencies;Hippocampus;improved;in vivo;innovation;Ion Channel;Knowledge;Ligands;Mediating;Membrane;Molecular;Molecular Target;mouse model;mutant;N-Methyl-D-Aspartate Receptors;neural;neural circuit;neuroinflammation;Neurons;neuroprotection;neuropsychiatry;neurosteroids;next generation;novel;novel therapeutics;Nuclear;Outcome;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Pharmacologic Actions;Physiology;positive allosteric modulator;programs;Proteins;Psychiatric therapeutic procedure;receptor;receptor function;Recombinants;Research;Signal Transduction;Site;steroid analog;Steroid Receptors;Steroids;Stress;Synapses;Techniques;Testing;Therapeutic;tool;Viral;voltage;Work

PROJECT_TITLE: Mechanistic studies of Neurosteroid Analogues


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: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative This is an application for renewal of a training grant for postdoctoral and clinical fellows in the area of Neurobiology of Aging and Alzheimer's Disease. The 29 faculty acting as Preceptors in the training program are chosen from the Arizona Alzheimer's Consortium and have complementary research interests that span basic and clinical science, including brain imaging, computer science, genomics, systems, cognitive and molecular neuroscience, experimental therapeutics and neuropathological approaches to the study of the aging brain and early detection and treatment of Alzheimer's disease (AD) and AD-related dementias (ADRD). The program offers a unique collaborative and interdisciplinary research experience designed individually for each Fellow to provide the next generation of independent investigators the tools needed to enable them to contribute in significant ways to an understanding of cognitive decline in aging, AD and ADRD, so that preventions and treatments can be effectively developed.

PI_NAMEs: BARNES, CAROL A. (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TITLE: Postdoctoral Training, Neurobiology of Aging and Alzheimer's Disease


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Genetics;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: We discovered that endorepellin, a soluble fragment of the heparan sulfate proteoglycan perlecan, evokes excessive autophagy or self-eating in the endothelial cells lining breast cancer vessels with no direct effects on the cancer cells. This novel bioactivity of endorepellin, via selective and specific targeting of the endothelia, will be investigated utilizing state-of-the-art molecular methodologies combined with highly-innovative mouse models of mammary carcinomas. Our research, by focusing on the tumor microenvironment and tumor secretome, will unravel unique avenues of study using endorepellin as a valuable treatment modality to combat this devastating disease in both primary and secondary malignancies.

PI_NAMEs: IOZZO, RENATO V. (contact)

PROJECT_TERMS: adhesion receptor;Affect;Affinity;aggressive breast cancer;Allografting;angiogenesis;Angiogenesis Inhibitors;Angiogenic Factor;Angiostatic Proteins;antagonist;attenuation;Autophagocytosis;Binding;Biological;Biology;Breast Cancer cell line;Breast Carcinoma;C-terminal;Cancer Biology;cancer cell;cell behavior;Cells;cellular engineering;Cellular Stress;Chemicals;clinically relevant;combat;Communication;Complex;confocal imaging;Core Protein;Cues;Development;Disease;Eating;EIF-2alpha;Endothelial Cells;Endothelium;Enzymes;Exons;experimental study;Fibroblast Growth Factor Receptors;Funding;Gene Targeting;Genetic;genetic signature;Genetic Transcription;Grant;Growth;HAS2 gene;Heparan Sulfate Proteoglycan;Hyaluronan;Immunologics;In Vitro;in vivo;inducible Cre;inhibitor;innovation;Integrins;interdisciplinary approach;KDR gene;Knowledge;Laboratories;Ligation;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Methodology;Modality;Modeling;Molecular;mouse model;mTOR inhibition;mTOR Inhibitor;Mus;mutant;Mutate;Names;nano-string;Neoplasm Metastasis;neoplastic cell;neovascularization;novel;novel therapeutics;Nutrient;nutrient deprivation;overexpression;Oxygen;paracrine;Parents;Parkin;Pathway interactions;perlecan;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphorylation Site;Phosphotransferases;predict clinical outcome;programs;promoter;Protein Tyrosine Phosphatase;Proteins;Proteoglycan;PTPN6 gene;receptor;Recombinants;Regulation;Research;Role;Second Primary Cancers;Sensitivity and Specificity;sensor;Signal Transduction;Specificity;Stromal Cells;Tamoxifen;Technology;Testing;Time;transcriptome;transcriptomics;Transgenic Mice;Translating;tumor;Tumor Angiogenesis;tumor microenvironment;tumor progression;tumorigenesis;tumorigenic;ultra high resolution;Vascular Endothelium;Vascularization;VEGFA gene;Women's mortality;Work;Zebrafish

PROJECT_TITLE: Proteoglycan regulation of tumor angiogenesis and endothelial cell autophagy


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Depression;Mental Health;Mental Illness;Neurosciences;Women's Health Research

PHR: Project Narrative The episodic nature of affective disorders suggests that switching between healthy and unhealthy brain and behavioral states is an inherent feature of some psychiatric illnesses. Neuroactive steroids (NAS) have been implicated in affective switching and have demonstrated persistent antidepressant effects, suggesting the ability to influence behavioral states. The current project will investigate the mechanisms through which NAS can alter network and behavioral states, which will potentially provide insight into the episodic nature of psychiatric illnesses as well as the antidepressant effects of NAS.

PI_NAMEs: MAGUIRE, JAMIE LYNN (contact)

PROJECT_TERMS: Acute;Affective;Allopregnanolone;Amygdaloid structure;Animal Model;Anti-Anxiety Agents;anti-depressive agents;antidepressant effect;behavior influence;Behavioral;Brain;brain cell;Brain region;cell type;Chemistry;Chronic;Clinical;Clinical Trials;Collaborations;Communication;CRISPR/Cas technology;Data;delta receptors;Drug Utilization;Formulation;Generations;Goals;Hippocampus;Human;in vivo;insight;Interneurons;intraperitoneal;intravenous administration;Knock-out;Knowledge;Link;Medial;Mediating;member;Mental disorders;Modeling;Mood Disorders;Nature;Neurons;neurosteroids;new technology;novel;Parvalbumins;Patients;Play;positive allosteric modulator;Postpartum Depression;Postpartum Period;Pre-Clinical Model;Prefrontal Cortex;Property;Psychiatric therapeutic procedure;receptor;Research Support;Risk Factors;Role;Site;Stress;Techniques;Testing;Therapeutic

PROJECT_TITLE: Elucidating the Mechanisms Mediating the Impact of Neuroactive Steroids on Network and Behavioral States


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Immunotherapy;Women's Health Research

ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Public health statement The death receptor Fas can kill cancer cells through induction of apoptosis, however in most cancers including breast cancer it is expressed by the cancer cells to drive and maintain tumor growth and facilitate metastases formation. Based on recent preliminary data by the PI this proposal will explore a novel immune suppressive activity of the Fas receptor and to overcome it when expressed on triple negative breast cancer, the breast cancer subtype with the poorest prognosis. Results from this proposed could result in an improved way to use immune therapy for the treatment of triple negative breast cancer where it has not yet been successful.

PI_NAMEs: PETER, MARCUS E. (contact)

PROJECT_TERMS: Antitumor Response;Binding;Binding Proteins;Biochemical;Biological Assay;Breast Cancer Cell;C-terminal;cancer cell;Cancer Etiology;cancer subtypes;cancer therapy;CD95 Antigens;Cells;Cessation of life;Clinic;Clinical;Complement;Complex;crosslink;cytokine;Data;derepression;design;Equilibrium;Fas Signaling Pathway;Genetic Recombination;Genetic Transcription;Genetically Engineered Mouse;Goals;Growth;Immune;immune activation;immune checkpoint;Immune checkpoint inhibitor;Immunocompetent;Immunosuppression;Immunotherapy;Implant;improved;In Vitro;in vivo;Induction of Apoptosis;Infiltration;Inflammatory;inhibitor;Killer Cells;Knock-out;Knockout Mice;Knowledge;Ligands;Lymphocytic Infiltrate;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Modeling;Molecular;molecular subtypes;Mouse Cell Line;mouse model;Mouse Strains;Mus;Myeloid-derived suppressor cells;Natural Killer Cells;Nature;Neoplasm Metastasis;neoplastic cell;NF-kappa B;NF-Kappa B p65;NMR Spectroscopy;novel;Outcome;p65;Patients;peptidomimetics;permissiveness;Production;Prognosis;Prognostic Factor;programs;protein complex;Public Health;receptor;recruit;Role;screening;Signal Transduction;single-cell RNA sequencing;small molecule libraries;targeted treatment;Testing;Tissues;TNFRSF5 gene;TNFRSF6 gene;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor microenvironment;Tumor Promotion;ubiquitin ligase;Woman;Work

PROJECT_TITLE: Novel immune suppressive activities of Fas/CD95 in triple negative breast cancer

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Brain Disorders;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness

PHR: Narrative The neurosteroid brexanolone has recently been approved for the treatment of postpartum depression and other neurosteroids are being evaluated for the treatment of major depressive disorder. The mechanism of action whereby neurosteroids ameliorate depression is currently unknown. This core will provide a panel of neurosteroid analogues with different mechanisms of action that will be used in Projects 1 – 3 to determine physiologic molecular targets and pathways that underlie the antidepressant actions of neurosteroids.

PI_NAMEs: COVEY, DOUGLAS F (contact)

PROJECT_TERMS: academic program;Allopregnanolone;analog;anti-depressive agents;Automobile Driving;Cell membrane;Cellular Stress;Chemistry;clinical efficacy;Clinical Research;Databases;Evolution;Impact evaluation;improved;Ion Channel;Major Depressive Disorder;Mental Depression;Molecular Target;N-Methyl-D-Aspartate Receptors;neurosteroids;novel;novel strategies;Pathway interactions;Pharmacotherapy;Photoaffinity Labels;Physiological;Postpartum Depression;Psychiatric therapeutic procedure;Psychiatry;receptor;Recording of previous events;Research Personnel;side effect;Site;Testing

PROJECT_TITLE: Chemistry Core


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Coronaviruses;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Narrative The human brain’s cerebellar connectome plays an important role in neurodevelopment and aging and has been implicated in a large number of diseases. However, a complete map of the human cerebellar structural connectome is still lacking due to multiple challenges that have thus far prevented comprehensive mapping of its complex intrinsic and extrinsic pathways. We propose to address these challenges to create the most comprehensive, anatomically curated maps of the intrinsic and extrinsic cerebellar connectome to date, which will enable the study of the cerebellar connectome in health and disease.

PI_NAMEs: MAKRIS, NIKOLAOS ;O'DONNELL, LAUREN JEAN (contact);RATHI, YOGESH

PROGRAM_OFFICER_NAME: BENNETT, YVONNE MARIE

PROJECT_TERMS: Address;Affect;Aging;Algorithms;Alzheimer's Disease;Anatomy;Atlases;autism spectrum disorder;Brain;Brain Diseases;Brain Stem;Cell Nucleus;Cerebellar Cortex;Cerebellar Nuclei;Cerebellum;Cerebral cortex;comparative;Complex;Computer software;Computing Methodologies;connectome;Data;data quality;Dedications;deep learning;deep learning algorithm;Diffusion Magnetic Resonance Imaging;Disease;Down's Syndrome;experimental study;Fascicle;Fiber;Generations;Goals;Grain;Head;Health;Human;human subject;Image;improved;in vivo;Individual;Joints;Literature;Maps;meter;Methodology;millimeter;Monkeys;Mutism;Nerve Degeneration;Neuroanatomy;neurodevelopment;Neurons;nonhuman primate;novel;Ontology;open source;Parkinson Disease;Pathway interactions;Play;Predisposition;prevent;Resolution;Role;Scanning;Schizophrenia;Spinal Cord;Structure;Synapses;System;Thalamic structure;Time;Tracer;tractography;Translating;ultra high resolution;Vendor

PROJECT_TITLE: Mapping of the intrinsic and extrinsic cerebellar connectome at ultra high resolution with expert neuroanatomical curation

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]