NIH_SPENDING_CATS: Cancer;Genetics;Hematology;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Germline RUNX1 mutations establish a preleukemic state in hematopoietic stem and progenitor cells that predispose affected individuals to developing acute leukemia. We will identify how transcriptomic changes and an inflammatory microenvironment alter hematopoiesis in germline RUNX1 mutation carriers. These data will provide a roadmap to monitor asymptomatic family members, devise therapeutic strategies to prevent or improve patient outcome, and will facilitate translation of these findings to other leukemia predisposition syndromes.

PI_NAMEs: AGARWAL, ANUPRIYA  (contact);GODLEY, LUCY ANN

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: 3-Dimensional;Acute leukemia;Affect;Biogenesis;biomarker identification;Bone Marrow;Bone Marrow Cells;Bone Marrow Diseases;Bone Marrow Transplantation;Candidate Disease Gene;CCL2 gene;Cell Differentiation process;Cell Survival;Cells;Chronic;Classification Scheme;Climacteric;Clinical;Clonal Expansion;Coculture Techniques;Collection;CRISPR/Cas technology;cytokine;Data;Defect;Development;Diagnostic;Differentiation and Growth;Disease;Disease Progression;DNA Damage;early detection biomarkers;Early identification;Elements;Environment;erythroid differentiation;Event;Evolution;experience;Exposure to;Extracellular Fluid;Familial Platelet Disorder;Family;Family member;First Degree Relative;Gene Expression;Genetic;Genetic Predisposition to Disease;Genetic Transcription;Germ Lines;Germ-Line Mutation;Goals;Growth;Guidelines;Hematopoiesis;Hematopoietic;hematopoietic differentiation;Hematopoietic Neoplasms;Hematopoietic stem cells;IL8 gene;Impairment;improved;improved outcome;In Vitro;in vivo;Individual;induced pluripotent stem cell;Inflammation;Inflammatory;Knowledge;leukemia;Leukemic Cell;Malignant Neoplasms;Mediating;Megakaryocytes;mesenchymal stromal cell;Modeling;Molecular;Monitor;monocyte;mouse model;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;mutation carrier;Myelogenous;novel;novel therapeutics;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;Platelet aggregation;Predisposition;Preleukemia;premalignant;prevent;Prevention;Prevention strategy;Production;progenitor;Prognostic Marker;programs;proto-oncogene protein Spi-1;rational design;Regulation;Resources;response;Ribosomes;Risk;Role;RUNX1 gene;Sampling;Screening for cancer;Signal Transduction;stem;stem cell self renewal;stem cells;Stress;Stromal Cells;Syndrome;Techniques;Testing;Therapeutic;therapeutic biomarker;therapeutically effective;Thrombocytopenia;Time;tool;transcriptomic profiling;transcriptomics;Transgenic Mice;Translations;transplant model;Up-Regulation;World Health Organization;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Hematopoiesis in germline RUNX1mutation carriers: impact of inflammation and the bone marrow niche

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


ADMINISTERING_IC: HL

ARRA_FUNDED: N

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Lung;Pulmonary Hypertension;Rare Diseases

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Pulmonary arterial hypertension (PAH) is a progressive disease of lung arteries that causes shortness of breath, heart failure, and death. C-terminal Src kinase (Csk) is a protein that may contribute to lung artery damage early in the course of disease. Treatments blocking Csk are anticipated to stop lung artery destruction and prevent shortness of breath, heart failure, and death from PAH.

PI_NAMEs: WERTHEIM, BRADLEY  (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: advanced disease;Advisory Committees;Anabolism;Area;Arterial Disorder;arterial stiffness;Arteries;Atomic Force Microscopy;Award;Binding;Biochemistry;Biological;Biological Assay;Blood Vessels;career development;Cells;Cessation of life;Clinical;Clinical Investigator Award;Collagen;Computer Models;Coupling;Data;Dedications;Deposition;Development;didactic education;Disease;Doctor of Medicine;Doctor of Philosophy;Early treatment;effective therapy;endothelial dysfunction;Endothelium;Fibrillar Collagen;Fibrosis;Functional disorder;Functional impairment;Funding;Gel;Gene Expression Profile;Heart failure;Hospitalization;Hospitals;Human;Hydrogen Peroxide;Hypoxia;Immunofluorescence Immunologic;Immunoprecipitation;Impairment;improved;in silico;In Vitro;in vivo;Inflammatory;Investigation;K-Series Research Career Programs;Lung;lung hypoxia;Mass Spectrum Analysis;Mediating;Mediator;Medical;medical schools;Medicine;Mentors;Mentorship;Modeling;Modification;Molecular;Monocrotaline;mortality;multicatalytic endopeptidase complex;novel;novel strategies;Outcome;overexpression;oxidant stress;oxidation;Oxidation-Reduction;Pathogenesis;Pathogenicity;Pathway Analysis;Pathway interactions;Phenotype;Phosphotransferases;Physicians;Physiologic intraventricular pressure;posttranscriptional;predictive modeling;Predisposition;Premature Mortality;prevent;Principal Investigator;programs;Progressive Disease;Proteasome Inhibition;Protein Tyrosine Kinase;protein-tyrosine kinase c-src;Proteins;Proteomics;Proto-Oncogenes;Publications;pulmonary arterial hypertension;pulmonary arterial pressure;Pulmonary arterial remodeling;pulmonary artery endothelial cell;Pulmonary artery structure;Pulmonary Hypertension;Pulmonary Vascular Resistance;Regulation;Research;Resistance;Right Ventricular Dysfunction;right ventricular failure;Right Ventricular Function;Right ventricular structure;Role;scaffold;Scientist;Shortness of Breath;Signal Transduction;Site-Directed Mutagenesis;Small Interfering RNA;Smooth Muscle Myocytes;src-Family Kinases;SU 5416;Substrate Interaction;Sulfhydryl Compounds;symposium;targeted treatment;Testing;Time;Training;Training Programs;transcriptomics;Treatment Efficacy;Ubiquitin;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitination;Vascular Diseases;Vascular remodeling;Ventricular;Western Blotting;Woman

PROJECT_TITLE: Ubiquitination and Endothelial Fibrosis in Early Pulmonary Arterial Hypertension

STUDY_SECTION: MCBS

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


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF PHARMACY

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Physical Injury - Accidents and Adverse Effects

ORG_CITY: LITTLE ROCK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: PROJECT NARRATIVE Victims of a nuclear event can be exposed to ionizing radiation, which has long-term adverse effects on their immune system. This application will investigate 2 mechanisms of radiation-induced immune dysregulation: 1) the interaction between platelet receptor glycoprotein Ibα (GPIbα) and leukocyte Mac-1 and 2) the production of platelet-derived microparticles (PMPs). We will test whether exogenous administration of GPIbα and blocking PMP production are viable strategies to mitigate the adverse effects of ionizing radiation.

PI_NAMEs: CANNON, MARTIN J;PATHAK, RUPAK  (contact);WARE, JERRY

PROGRAM_OFFICER_NAME: WINTERS, THOMAS A

PROJECT_TERMS: Acute;adaptive immune response;Address;Adverse effects;Age;Anti-Inflammatory Agents;Antibodies;Area;Autoimmune Diseases;B-Lymphocytes;Binding;Biological;Blood Platelets;bone cell;Bone Marrow;Cardiovascular Diseases;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Physiology;Cells;Circulation;cytokine;Data;Dendritic Cells;Development;Dose;Event;Exhibits;Experimental Models;Exposure to;FDA approved;Functional disorder;gastrointestinal;Generations;Glucosamine;Glycoproteins;Growth Factor;Health;Heart;heart function;Histology;Hour;Human;IL2RA gene;Immune;immune function;Immune system;Immune System Diseases;immunoregulation;Immunosuppression;In Vitro;in vivo;Incubated;Individual;Inflammation;Inflammatory;Innate Immune System;insight;Interleukin 4 Receptor;intestinal injury;Intestines;Ionizing radiation;ITGAM gene;ITGAX gene;Knockout Mice;leukocyte activation;Leukocytes;Ligand Binding Domain;Macrophage;Macrophage-1 Antigen;medical countermeasure;member;monocyte;morphometry;mouse model;Mus;mutant mouse model;N-terminal;neutrophil;novel;Nuclear Accidents;Organ;organ injury;particle;Pathologic;Persons;Pharmaceutical Preparations;Phenotype;Plasma;Platelet Activation;Platelet Glycoproteins;Play;polymicrobial sepsis;primary endpoint;Production;Radiation;Radiation Accidents;Radiation exposure;Radiation induced damage;Radiation Injuries;radiation mitigator;Radiation Protection;radiological attack;receptor;Regulation;Regulatory T-Lymphocyte;Research;response;Risk;RNA;Role;secondary endpoint;Serum;small molecule;Spleen;submicron;systemic inflammatory response;Testing;Vaccination;Whole-Body Irradiation;Wild Type Mouse

PROJECT_TITLE: Platelets in radiation-induced immune dysregulation


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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

ORG_CITY: DALLAS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE Obesity and non-alcoholic fatty liver disease (NAFLD) results in perturbed liver function which can be improved by lifestyle interventions. The pathophysiology of NAFLD and its treatments, such as exercise, are associated with changes in sympathetic nervous system activity. The purpose of this proposal is to elucidate the role of liver sympathetic nervous system in control of hepatic metabolic flux during obesity in vivo and to determine how it is modulated by exercise, with a particular focus on mitochondrial function, hepatic glucose and ketone production.

PI_NAMEs: DEJA, STANISLAW MAREK (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Acute;Adrenergic Receptor;Aerobic;Aerobic Exercise;Affect;Amino Acids;Body Weight decreased;career development;Cell Respiration;Chronic;Citric Acid Cycle;Complication;cost;Development Plans;Diabetes Mellitus;Discipline;Disease;Event;Exercise;exercise capacity;Exhibits;Fatty acid glycerol esters;Fatty Liver;fighting;Functional disorder;Genetic;Gluconeogenesis;Glucose;glucose production;Glycogen;Goals;Healthcare;Hepatic;hepatic gluconeogenesis;Hepatocyte;High Fat Diet;Human;Impairment;improved;in vivo;Infusion procedures;Insulin;Intervention;ketogenesis;ketogentic;Ketones;Knockout Mice;Knowledge;lifestyle intervention;lipid metabolism;Lipids;Liver;liver function;liver metabolism;Mediating;Metabolic;Metabolic Control;Metabolism;metabolomics;Mitochondria;Monitor;Mus;Neurons;neurophysiology;non-alcoholic fatty liver disease;Norepinephrine;novel;Obese Mice;Obesity;Output;oxidation;Pathway interactions;Physical activity;Physiology;Play;Prevalence;Process;Production;Protocols documentation;receptor binding;receptor function;Receptor Signaling;Regulation;remediation;Research;Research Personnel;response;Role;Route;Running;Scientist;Signal Transduction;Skeletal Muscle;stable isotope;Stimulus;Stress;Sympathetic Nervous System;Testing;Tissues;tool;Tracer;Training;Training Programs;treadmill;Triglycerides

PROJECT_TITLE: Sympathetic Control of Liver Metabolism in Exercise and Obesity

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK(M1)-1-C]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Mental Health;Neurosciences

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Dysregulation of inhibitory synapses, specifically GABAARs, alters excitatory-inhibitory balance and has been implicated in a number of neurological disorders, including ischemia. GABAAR trafficking regulates overall inhibitory synaptic strength and is influenced by phosphorylation status of the receptor. Here, I propose to test the hypothesis that GABAAR trafficking during OGD is differentially regulated based on neuronal populations, and this contributes to defined synaptic and cellular alterations based on the susceptibility of these neuronal populations.

PI_NAMEs: GARCIA, JOSHUA DAYLON (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: autism spectrum disorder;Behavior;Behavioral Assay;behavioral phenotyping;Brain;Brain region;Calcineurin;Calcium;Cell Death;Cell Death Induction;Cell membrane;Cell Surface Receptors;cell type;Cerebral Ischemia;Clathrin;Cognition;Data;deprivation;Development;Disease;Down-Regulation;Electrophysiology (science);Endocytosis;Equilibrium;Event;Excision;Excitatory Synapse;experience;Functional disorder;Future;Glucose;hippocampal pyramidal neuron;Hippocampus;Impairment;In Vitro;in vivo;in vivo imaging;in vivo Model;Inhibitory Synapse;interest;Investments;Ischemia;Knowledge;Laboratories;Learning;Mediating;Memory;Mentors;Modeling;Molecular;mouse model;Mutation;Nervous System Disorder;Neurodevelopmental Disorder;neuronal circuitry;neuronal excitability;Neurons;novel;Output;Oxygen;Pathogenicity;Pathologic;Pathology;Phosphoric Monoester Hydrolases;Phosphorylation;Play;Population;Postdoctoral Fellow;postsynaptic;Predisposition;Presynaptic Terminals;prevent;programs;Protein Dephosphorylation;Protein Phosphatase 2A Regulatory Subunit PR53;receptor;Receptor Down-Regulation;receptor downregulation;receptor expression;receptor internalization;Regulation;Research;Research Project Grants;Resistance;Role;scaffold;Schizophrenia;Serine;Signal Pathway;Signal Transduction;Site;Slice;Surface;Synapses;synaptic inhibition;Synaptic plasticity;Technical Expertise;Testing;Therapeutic Intervention;trafficking;Up-Regulation;Vulnerable Populations;Work

PROJECT_TITLE: The role of dendritic excitatibility in controlling GABAergic synapse maturation


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_NAME: TUFTS MEDICAL CENTER

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because therapeutic advances in treating bone metastases is likely to reduce the large number of deaths that disproportionately affects men of African and Caucasian descent. The proposed research is aligned with the NIH/NCI mission to develop fundamental knowledge in order reduce the burden of suffering and premature death from cancer.

PI_NAMEs: MATHEW, PAUL  (contact)

PROGRAM_OFFICER_NAME: HARRIS, RAYMOND D

PROJECT_TERMS: Acceleration;Adhesives;advanced disease;Affect;African;Androgen Receptor;Animal Model;Anoikis;Antibodies;Antibody Therapy;Autopsy;Behavior;Benign;biobank;Biological Markers;Bispecific Antibodies;bone;Bone Marrow;Breast;Castration;Caucasians;Cell Communication;Cessation of life;Characteristics;Chemotaxis;Clinical;clinical research site;Clinical Trials;crosslink;Data;Dimensions;Disease;Disease Progression;Down-Regulation;efficacy evaluation;Elements;Endothelium;Epithelium;Experimental Models;Fibronectins;Functional disorder;Generations;Genetic;Goals;Growth;Homing;Human;Image;Immunodeficient Mouse;improved;In Vitro;in vivo;in vivo Model;innovation;Integrin alpha5beta1;Integrin alphaV;Integrin Binding;Integrins;ITGA5 gene;Kidney;Knowledge;Laboratory Study;Life;Link;Lung;lymph nodes;Malignant Breast Neoplasm;Malignant neoplasm of prostate;Malignant Neoplasms;Matrix Metalloproteinases;Measures;Mediating;men;Mesenchymal;mesenchymal stromal cell;Metastatic Neoplasm to the Bone;Metastatic Prostate Cancer;migration;Mission;Molecular;Molecular Mechanisms of Action;Neoplasm Metastasis;neoplastic cell;Noninfiltrating Intraductal Carcinoma;novel;novel therapeutic intervention;Organ;Organ Specificity;Outcome;Pathway interactions;patient derived xenograft model;Patients;Pattern;pharmacodynamic biomarker;Phenotype;premature;Prostate Adenocarcinoma;prostate cancer cell;prostate cancer metastasis;prostate cancer progression;Prostatic Neoplasms;Public Health;Quality of life;receptor;Research;Resistance;response;Role;Signal Transduction;Skeleton;Solid Neoplasm;Specificity;Stromal Cells;survival outcome;Testing;Therapeutic;Therapeutic antibodies;tissue resource;Treatment Efficacy;tumor;Tumor Burden;United States National Institutes of Health;Up-Regulation;Visceral

PROJECT_TITLE: Control of lethal prostate cancer with a bispecific av and a5b1 integrin antibody

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Digestive Diseases;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: STANFORD

ORG_DEPT: SURGERY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on the clinical translation of a new antibody-based optical fluorescent technology for ultrasensitive detection of occult pancreatic cancer in vivo. The anticipated validation of this intraoperative molecular imaging method in identifying very small (1-3mm3) pancreatic cancer deposits will not only enhance surgical staging and outcomes for this highly lethal cancer, but can also lay the foundation for the development of new horizons for earlier detection of this challenging malignancy. As essentially every patient diagnosed with pancreatic cancer currently will eventually die of this disease, the proposed research is relevant to the part of the NIH’s mission that pertains to reducing illness and disability.

PI_NAMEs: POULTSIDES, GEORGE  (contact)

PROGRAM_OFFICER_NAME: LIN, CHARLES

PROJECT_TERMS: Antibodies;Beds;Cancer Detection;Cetuximab;Clinical;clinical efficacy;Clinical Research;clinical translation;cost effective;curative treatments;Data;Decision Making;Deposition;Detection;Development;Diagnosis;diagnostic accuracy;disability;Disease;Disease-Free Survival;Disseminated Malignant Neoplasm;Distant;Early Diagnosis;efficacy evaluation;Eligibility Determination;Epidermal Growth Factor Receptor;Excision;Eye Surgeon;Failure;Fc Receptor;first-in-human;Fluorescence;fluorescence imaging;Foundations;Goals;Human;Image-Guided Surgery;imaging agent;imaging modality;imaging scientist;Imaging technology;improved;in vivo;Infiltration;Infusion procedures;innovation;Label;lymph nodes;Malignant neoplasm of pancreas;Malignant Neoplasms;Mission;Modality;molecular imaging;Neoplasm Metastasis;novel strategies;Oncologist;Operative Surgical Procedures;Optics;Outcome;overexpression;Palpation;Pancreatic Adenocarcinoma;pancreatic neoplasm;panitumumab;Pathologist;Patient-Focused Outcomes;Patients;Peritoneal;Peritoneum;Primary Neoplasm;prospective;Public Health;radiological imaging;radiologist;Radiology Specialty;Recurrent disease;Refractory;Research;Resected;Residual Neoplasm;Residual state;response;safety and feasibility;Sensitivity and Specificity;Site;Specificity;Specimen;Staging;Surgeon;Surgical margins;Technology;Therapeutic;Time;tool;tumor;United States National Institutes of Health;Validation;Visualization

PROJECT_TITLE: Highly Sensitive Detection of Occult Pancreatic Cancer Using Intraoperative Molecular Imaging

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: ANN ARBOR

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Understanding why we sleep remains one of the most enduring mysteries in science and is essential for addressing the role of sleep in neurological diseases. Here we apply innovative molecular tools to decipher the components of the sleep homeostat that determines how much and well we sleep.

PI_NAMEs: ALLADA, RAVI  (contact)

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: Address;Alzheimer's Disease;Animal Model;Behavior;Brain;Brain Diseases;Brain region;Caring;Cells;Central Nervous System;circadian regulation;Diabetes Mellitus;Disease;Drosophila genus;Eating;Exhibits;experience;Genes;Genetic;Genomics;innovation;insight;Jellyfish;Label;life span;Link;Logic;memory consolidation;Mental Depression;Molecular;Nervous System Disorder;neuromechanism;Neurons;Obesity;Organism;Partner in relationship;Proteins;Proteomics;Resolution;Role;Science;single-cell RNA sequencing;Sleep;Sleep Deprivation;sleep regulation;Taxes;tool;transcriptomics;Wakefulness

PROJECT_TITLE: The Molecular and Cellular Basis of the Sleep Homeostat


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Cancer;Prevention

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE Research in cancer prevention and control is a key to combat both the incidence of and suffering associated with cancer, particularly among `priority' populations such as racial/ethnic minorities, low-income, and older adults. Our program has been highly successful in its first funding cycle with recruitment of a very diverse group of trainees, having 100% of graduates in full-time academic research careers focused on cancer prevention and control, and 75% having already obtained external K (or equivalent) funding. We are applying for a renewal of this postdoctoral research training program to train the next generation of independent cancer researchers through tailored curricular and research experiences that promote interdisciplinary approaches to cancer prevention and control.

PI_NAMEs: MONTGOMERY, GUY H;WISNIVESKY, JUAN P (contact)

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Cancer Control;cancer prevention;Population;Training Programs

PROJECT_TITLE: Training Program in Cancer Prevention and Control for Priority Populations

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Institutional Training and Education Study Section (F)[NCI-F]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: CHAMPAIGN

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

ORG_STATE: IL

PHR: PROJECT NARRATIVE To form successful multidisciplinary research teams of chemists and biologists with the ability to solve longstanding problems that impact human health, chemists and biologists must have an understanding of the language, concepts, and techniques of each group. The Chemistry-Biology Interface Training Program (CBI-TP) at the University of Illinois, Urbana-Champaign addresses this critical need through a variety of activities aimed at training the next generation of scientists with expertise at the chemistry-biology interface.

PI_NAMEs: HERGENROTHER, PAUL  (contact)

PROGRAM_OFFICER_NAME: PAUL, MOUSHUMI

PROJECT_TERMS: Biology;Chemistry;Training Programs

PROJECT_TITLE: Training Program at the Chemistry Biology Interface

STUDY_SECTION: TWD

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


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cancer;Clinical Research;Digestive Diseases;Dissemination and Implementation Research;HPV and/or Cervical Cancer Vaccines;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Patient Safety;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Rare Diseases;Sexually Transmitted Infections;Social Determinants of Health;Vaccine Related;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

ORG_STATE: PA

PHR: Project Narrative Human Papillomavirus (HPV) is a common sexually transmitted infection that can cause anal cancer. Currently there is a vaccine available that can prevent HPV infection and subsequent anal cancers. In this study, innovative marketing evaluation techniques will be used to create patient education health messages focused on anal cancer prevention for high-risk populations.

PI_NAMEs: WHELDON, CHRISTOPHER W. (contact)

PROGRAM_OFFICER_NAME: WHITE, DOLLY PENN

PROJECT_TERMS: 3-Dimensional;Address;Adolescent;Adult;Age;age related;aged;AIDS prevention;Anal Sex;Anus;Bass;Behavioral;black men who have sex with men;Black race;cancer health disparity;cancer prevention;cancer risk;care delivery;Caring;cis-female;cisgender;Clinic;clinical decision-making;Decision Making;Development;Dose;education resources;Effectiveness;Eligibility Determination;Equity;ethnoracial;Evaluation;Exposure to;Face;Feedback;Female;Focus Groups;Future;Gender;General Population;Health;health communication;Health Disparities Research;Health Insurance;Healthcare;Healthcare Systems;high risk;high risk population;Hispanic;HPV vaccine acceptance;HPV vaccine hesitancy;Human papilloma virus infection;Human Papilloma Virus Vaccination;Human Papilloma Virus Vaccine;Human Papillomavirus;implementation strategy;improved;Incidence;Individual;innovation;intersectionality;Intervention;Interview;Lesion;Malignant neoplasm of anus;Malignant neoplasm of cervix uteri;Maps;Marketing;Mathematics;Medical;men who have sex with men;men's group;Methods;Modeling;mortality;Motivation;National Institute on Minority Health and Health Disparities;Needs Assessment;novel;novel strategies;Oncogenic;Outcome;Patient Education;patient engagement;patient-clinician communication;Patients;Population Heterogeneity;pre-exposure prophylaxis;preference;premalignant;prevent;prevention service;Preventive service;primary care setting;prototype;Provider;Recommendation;Research;Risk;Risk Factors;Sampling;screening guidelines;Sexually Transmitted Diseases;skills;social stigma;Surveys;syndemic;System;Techniques;Testing;tool;transgender women;uptake;vaccine access;vector;Visual;Women's Group

PROJECT_TITLE: Development and user testing of a culturally targeted anal cancer prevention decision tool

STUDY_SECTION: ODHS

STUDY_SECTION_NAME: Organization and Delivery of Health Services Study Section[ODHS]


PHR: PROJECT NARRATIVE The mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals in order to control cell physiology. Increased mTORC1 activation is frequently observed in human disease, including cancer, type 2 diabetes, metabolic disorders, and neurodegeneration. The goal of this MIRA is to elucidate the molecular mechanisms by which mTORC1 is regulated by upstream stimuli. Completion of this project will provide valuable insight about mTORC1 biology and will uncover novel therapeutic targets.

PI_NAMEs: JEWELL, JENNA L (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Amino Acids;Autophagocytosis;Biology;cell growth;Cell Physiology;Clinic;Complex;Disease;FRAP1 gene;G-Protein-Coupled Receptors;Goals;human disease;insight;Malignant Neoplasms;Mediating;Metabolic Diseases;Metabolism;Molecular;Multiprotein Complexes;Nerve Degeneration;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;Phosphotransferases;Regulation;Signal Transduction;Sirolimus;small molecule;Stimulus;success

PROJECT_TITLE: mTORC1 Regulation by Upstream Stimuli

STUDY_SECTION: MRAC

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


NIH_SPENDING_CATS: Childhood Obesity;Clinical Research;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Nutrition;Obesity;Pediatric;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: HOUSTON

ORG_DEPT: PEDIATRICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE (Relevance Statement) Just as individual genetic variation can affect risk of obesity, so too can individual epigenetic variation. In particular, special genomic regions called CoRSIVs, which we recently discovered by screening in Caucasians, offer the best opportunity to advance our understanding of epigenetic etiology of obesity because their stable and systemic nature means that – like genetic polymorphisms – they can be assessed in any easily obtainable tissue sample, such as peripheral blood. Since we know there are many more human CoRSIVs to discover, and given that African Americans are disproportionately burdened by obesity, it is now urgent to screen for CoRSIVs directly in African Americans, and determine whether interindividual epigenetic variation at these regions affects risk of obesity.

PI_NAMEs: WATERLAND, ROBERT A (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Adipocytes;Affect;African;African American;African American population;African ancestry;Age;Archives;Area;Asian population;Birth;bisulfite sequencing;Blood;Body mass index;Brain;California;Caucasians;cell type;Child;Childhood;Cohort Studies;computational pipelines;Consent;Cross-Sectional Studies;Custom;Data;Databases;Development;DNA;DNA Methylation;Ectoderm;Embryo;Endoderm;energy balance;Environment;Epidemiology;epidemiology study;Epigenetic Process;epigenetic regulation;epigenetic variation;epigenomics;Etiology;Exhibits;Eye diseases;Gene Expression;Genes;Genetic;genetic epidemiology;Genetic Polymorphism;Genetic Variation;genome sequencing;genome-wide;Genomic DNA;Genomic Segment;Genomics;Germ Layers;Heart;Heritability;Human;Hypothalamic structure;Individual;Individuality;inter-individual variation;Los Angeles;Maps;Measurement;Measures;Mediating;Mesoderm;Metabolic Diseases;Methylation;methylation pattern;Mitotic;multi-ethnic;Nature;Neurons;Newborn Infant;novel;Obesity;obesity in children;obesity prevention;obesity risk;Organ;Overweight;Paper;Participant;peripheral blood;Population;programs;prospective;Prospective Studies;Public Health;Publishing;racial minority population;Reporting;Risk Factors;risk prediction;Role;Sampling;scale up;screening;Social Justice;Spottings;Testing;Thyroid Gland;Tissue Sample;Tissues;transcriptome sequencing;United States National Institutes of Health;Validation;Variant;Weight;whole genome

PROJECT_TITLE: Systemic interindividual epigenetic variants in African Americans: Identification, characterization, and prospective associations with obesity

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


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

ORG_NAME: RESEARCH INST OF FOX CHASE CAN CTR

PHR: PROJECT NARRATIVE The proposed project will contribute to a greater understanding of health trajectories among Chinese immigrants across different neighborhood settings, and will clarify the mechanisms by which neighborhoods foster social connections in this fast-growing but understudied population. The data obtained will inform our understanding of how best to invest in communities to increase engagement, social connectedness, and improve health.

PI_NAMEs: FANG, CAROLYN Y. (contact);TSENG, MARILYN

PROGRAM_OFFICER_NAME: JONES, NANCY LYNNE

PROJECT_TERMS: Acculturation;Address;Affect;African;allostatic load;Anthropometry;Asian;Asian Americans;Asian population;Behavioral;Biological;biological adaptation to stress;Blood Pressure;Blood specimen;Businesses;Cardiovascular system;Chinese;Chinese American;Chronic;Chronic Disease;Church;cohort;Communities;Data;Data Collection;density;disorder risk;Ethnic Origin;Ethnic Population;experience;Family;Fasting;Feeling;follow-up;Fostering;Glucocorticoids;Growth;Health;Human;Immigrant;Immigration;Immune;improved;Individual;Inflammatory;Institution;Insulin Resistance;Investigation;Investments;Language;Latinx;Life;Location;Loneliness;Measures;Metabolic;migration;Neighborhoods;Neurosecretory Systems;outreach;Pathway interactions;Persons;Philadelphia;Physiological;Play;Population;Questionnaires;racial population;recruit;Religion;Reporting;Research;residence;Resources;Role;Services;Shapes;social;Social Development;social engagement;Social Identification;Social isolation;Social Network;social space;social structure;Social support;Societies;Stress;stressor;Structure;Subgroup;support network;Time;Travel;United States;Visit;Volunteer Group;Vulnerable Populations;Work

PROJECT_TITLE: Neighborhood, social connectedness, and allostatic load in US Chinese immigrants

STUDY_SECTION: CIHB

STUDY_SECTION_NAME: Community Influences on Health Behavior Study Section[CIHB]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: CITY COLLEGE OF NEW YORK

PHR: Project Narrative Spinal cord stimulation (SCS), a pain-relief technique that delivers electrical current continuously to the spinal cord to mask pain signal before it reaches the brain, is a transformative therapy for hundreds of thousands of people suffering from chronic pain; taking on an extra urgency given the pressures from the ‘opioid epidemic’ and the substantial harm addictive drugs may have on patients. This proposal will provide the first comprehensive mechanism of action (heating-base gate-control) for a clinically transformative innovation in SCS: high frequency (kHz) SCS that provides pain relief (analgesia) without the tingling side-effects (paresthesia). The proposed research is relevant to public health because it will provide a detailed and experimentally-buttressed mechanism for kHz SCS thereby enhancing ongoing use and improved technology, and highly relevant to the BRAIN initiative’s mission by accelerating the development and application of innovative perturbation technologies.

PI_NAMEs: BIKSON, MAROM  (contact)

PROGRAM_OFFICER_NAME: HWANG, GRACE MEI-HUA

PROJECT_TERMS: 3-Dimensional;3D Print;Absence of pain sensation;Acceleration;Action Potentials;Acute;Address;Anatomy;Animal Disease Models;Architecture;base;biophysical model;Biophysical Process;biophysical properties;Blood flow;Brain;BRAIN initiative;Cell model;chronic pain;Clinical;clinical efficacy;Clinical Trials;clinically relevant;Code;computational network modeling;Computer Models;computerized tools;Convection;Coupled;Coupling;Custom;Data;Dependence;design;Development;Device Designs;Devices;disease model;Dorsal;dorsal horn;Dose;electric field;Electric Stimulation;Electrodes;Electrophysiology (science);Family suidae;FDA approved;Foundations;Frequencies;Goals;Heating;Heterogeneity;Human;Hydrogels;Implant;improved;in vivo;in vivo Model;innovation;Interneurons;Intervention;Lead;Maps;Marketing;Masks;Measurement;Membrane;Metabolism;Methods;Mission;Modality;Modeling;Molds;network models;neural stimulation;Neurobiology;neuromechanism;Neurons;neuroregulation;Neurostimulation procedures of spinal cord tissue;next generation;novel;opioid epidemic;Outcome;Pain management;pain processing;pain relief;pain signal;Paresthesia;Patients;Perfusion;Persons;Pharmaceutical Preparations;Phase;Physics;Physiologic pulse;porcine model;Porosity;predictive modeling;predictive tools;pressure;Printing;Procedures;product development;Property;Public Health;Research;Resolution;response;safety testing;sensor;side effect;Spatial Distribution;spatiotemporal;Spinal;Spinal Canal;Spinal Cord;System;Techniques;Technology;Temperature;Testing;theories;Time;Tissues;tool;Validation;Vertebral column;Width;Work

PROJECT_TITLE: kHz frequency Spinal Cord Stimulation: Novel Temperature-Based Mechanisms of Action


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

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Project Narrative BRCA1 is a well-established tumor suppressor that is frequently mutated in sporadic and hereditary breast and ovarian cancer. BRCA1 plays a critical, but poorly understood role in regulating various chromatin-signaling pathways that control access to genomic DNA. Understanding how these pathways normally protect the genome and the consequences of their dysfunction will provide important insight into how cancer cells develop and respond to specific chemotherapeutic treatments.

PI_NAMEs: LONG, DAVID THOMAS (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Apoptosis;Architecture;Biology;BRCA1 gene;cancer cell;Cell Cycle Progression;Cell-Free System;Chromatin;chromatin modification;chromatin remodeling;Chromatin Structure;Coupled;Coupling;Defect;Development;DNA;DNA biosynthesis;DNA Repair;egg;Embryo;Event;Functional disorder;Gene Expression;Genetic Transcription;Genome;genome integrity;Genomic DNA;Genomics;Hereditary Breast and Ovarian Cancer Syndrome;insight;Link;Maintenance;Mutate;Pathway interactions;Physical condensation;Plasmids;Play;Process;Regulation;repaired;response;Role;sensor;Signal Pathway;Signal Transduction;Stress;Support System;System;Therapeutic;tool;Tumor Suppressor Proteins;Xenopus

PROJECT_TITLE: BRCA1 and the regulation of chromatin dynamics in gene expression

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Neurosciences;Prevention

ORG_CITY: LOS ANGELES

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative  Despite the potential for generativity interventions to improve health and well-being in older adults, this has been a highly understudied area of research. As such, the goal of this project is to test the effect of a writing-based generativity intervention on well-being and inflammatory markers in a sample of older adults, as well as to examine the neurobiological mechanisms behind any observed effects. The results of this study may inform a low-effort, low-cost tool to improve well-being in older adults and thus may have broad implications for public health.

PI_NAMEs: EISENBERGER, NAOMI ILANA (contact)

PROGRAM_OFFICER_NAME: STOECKEL, LUKE

PROJECT_TERMS: Affect;Aging;Amygdaloid structure;Area;Biological Markers;Biology;Blood;caregiving;Caring;Control Groups;cost;Dedications;design;disability risk;expectation;Feeling;Gene Expression;Generations;Goals;group intervention;Health;Health Promotion;human old age (65+);Immune;improved;Inflammation;Inflammatory;inflammatory marker;innovation;insight;Intervention;late life;Learning;Link;Literature;Measures;Mediating;Mental Health;Methods;mortality;neural;neurobiological mechanism;Neurobiology;neuroimaging;neuromechanism;novel;older adult;Participant;Pathway interactions;Patient Self-Report;Perception;Personal Satisfaction;Physical activity;physical conditioning;Pilot Projects;Play;Population;post intervention;Productivity;Psyche structure;psychologic;psychological distress;Public Health;Publishing;Randomized;Research;Resources;response;Role;Sampling;Septal Area;social;System;Testing;tool;Ventral Striatum;Well in self;Writing

PROJECT_TITLE: Exploring the Neural Mechanisms Underlying the Effects of Generativity on Well-Being

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


NIH_SPENDING_CATS: Cancer;Clinical Research;Digestive Diseases;Pancreatic Cancer;Prevention;Rare Diseases

PHR: PROJECT NARRATIVE Despite our reliance on pancreatic cyst fluid biochemical and cytological analyses to guide clinical decision- making for patients with pancreatic cystic lesions, little effort has been directed toward optimization of biospecimen processing for pancreatic cyst fluid. We will systematically (1) evaluate the impact of preanalytical variables on pancreatic cyst fluid biochemical and cytological analyses and (2) identify strategies to mitigate the small volumes of available pancreatic cyst fluid in order to (3) develop a streamlined, reproducible protocol that improves the reliable early detection of pancreatic cancer. By improving the reproducibility and diagnostic yield of our assays for the detection of mucinous pancreatic cysts, we will increase the proportion of patients with pancreatic cystic lesions that undergo complete diagnostic testing, thereby improving the early diagnosis of pancreatic cancer while avoiding the burdens of overdiagnosis and overtreatment.

PI_NAMEs: KIRKWOOD, KIMBERLY SAUNDERS (contact)

PROGRAM_OFFICER_NAME: GUAN, PING

PROJECT_TERMS: Adenocarcinoma;Amylases;Aspartic Endopeptidases;aspirate;Attention;Biochemical;Biological;Biological Assay;Blood;Carcinoembryonic Antigen;Cells;Cellularity;Clinical;clinical biomarkers;clinical decision-making;clinical practice;clinical translation;Collaborations;Collection;Cyst;Cyst Fluid;Cytology;Data;detection assay;detection limit;Diagnosis;Diagnostic;diagnostic accuracy;Diagnostic tests;Dysplasia;Early Diagnosis;Epithelial Cells;Evaluation;Excision;Fluorescence;Freezing;gastricsin;Gastroenterology;Glucose;Health Care Costs;High grade dysplasia;improved;Industry;Intervention;Liquid substance;Malignant - descriptor;Malignant neoplasm of pancreas;Mass Spectrum Analysis;Morbidity - disease rate;mortality risk;Mucinous;Mucins;Mucous body substance;Needles;Neoplasms;neoplastic;novel;Operative Surgical Procedures;overtreatment;Pancreatic Adenocarcinoma;Pancreatic Cyst;Pancreatic cystic neoplasia;Pathology;Pathway interactions;Patients;Peptide Hydrolases;Performance;Pharmaceutical Chemistry;Procedures;prospective;Protocols documentation;Publishing;radiological imaging;Reader;Reproducibility;risk stratification;Running;sample collection;Sampling;Serine Protease;Serum;Site;standard of care;Standardization;Stomach;Technology;Temperature;Testing;tool;tripeptidyl aminopeptidase;United States;Viscosity;Warm Ischemia

PROJECT_TITLE: Advancing the Clinical Translation of Cyst Fluid Assays for Early Detection of Pancreatic Cancer


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

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE/PUBLIC HEALTH SIGNIFICANCE The proposed research is relevant to public health because new neurotechnologies in development represent the most promising pathway to much-needed new treatments for neuropsychiatric disorders, but existing disparities and research practices raise concerns about whether new advances will be developed for and disseminated to groups of greatest need. A rigorous examination of disparities and other ethical challenges in dissemination is critical to ensure that the public investment in BRAIN Initiative-funded neurotechnology achieves the broad aim of improving treatment for brain disorders.

PI_NAMEs: CHIONG, WINSTON  (contact);DOHAN, DANIEL P.

PROGRAM_OFFICER_NAME: CHURCHILL, JAMES D

PROJECT_TERMS: Address;Adoption;Affect;Attention;Attitude;Brain;brain based;Brain Diseases;BRAIN initiative;Caring;Clinic;Clinical;Collaborations;Communities;community advisory board;community engaged research;community engagement;comparative;Complex;Consensus;Consent;COVID-19 pandemic;Democracy;Development;Devices;disability;Disparity;Ensure;Epilepsy;Equity;Ethics;ethnic disparity;Ethnic Origin;Ethnography;family burden;FDA approved;Funding;Future;geographic disparity;Goals;health equity;Health Promotion;Housing;Implant;improved;individual patient;Information Dissemination;innovation;insight;Institution;Institutional Racism;International;Internet;Intervention;Interview;Investments;Justice;Leadership;member;Methods;Mind;Mission;neglect;neural implant;neuroethics;Neurology;neuropsychiatric disorder;neuropsychiatry;neuroregulation;Neurosciences;neurotechnology;new technology;novel;novel strategies;novel therapeutics;Participant;Pathway interactions;Patient Care;Patient Compliance;Patients;Persons;Population;Privacy;prospective;Psychiatry;Public Health;Race;racial disparity;Recording of previous events;recruit;Religion;Reporting;Research;Research Methodology;Research Personnel;Risk;Role;Sampling;Science;science and society;side effect;social;Social Problems;Social Sciences;socioeconomic disparity;Socioeconomic Status;Specialized Center;Surveys;Techniques;Technology;tool;Underserved Population;United States National Institutes of Health;Universities;Victimization;Work

PROJECT_TITLE: Anticipating ethical challenges and disparities in the dissemination of novel neurotechnologies


NIH_SPENDING_CATS: Bioengineering;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Hepatitis;Liver Disease;Machine Learning and Artificial Intelligence;Organ Transplantation;Precision Medicine;Prevention;Transplantation

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Narrative Liver transplantation (LT) is the only effective cure for end-stage liver disease. Post-LT NASH fibrosis is a major concern for patient health. Our goal is to develop new computational and experimental methods and discover new biomarkers for post-LT fibrosis that can efficiently identify at-risk individuals. A second goal of the project is to identify molecular mechanisms of post-LT fibrosis, which could be targeted therapeutically.

PI_NAMEs: ARTEEL, GAVIN E (contact);BENOS, PANAGIOTIS V;DUARTE-ROJO, ANDRES ;MERCHANT, MICHAEL L

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: Acceleration;acute liver injury;Address;algorithm development;Algorithms;Area;Biological;Biological Markers;Biology;biomarker discovery;biomarker identification;Cardiovascular Diseases;Cells;Chronic;Cirrhosis;Clinical Data;clinically actionable;clinically significant;cohort;Collagen;Data;design;Development;Disease;effective therapy;end stage liver disease;Extracellular Matrix;Extracellular Matrix Proteins;fatty liver disease;Fibrosis;Generations;Goals;Graph;graph learning;Health;Hepatic;Homeostasis;Human;Incidence;Individual;individual patient;insight;interest;Lead;learning algorithm;Lifestyle Therapy;Link;Liquid substance;liver development;Liver Fibrosis;liver injury;liver transplantation;machine learning method;Matrix Metalloproteinases;Mediating;Medical;Methods;minimally invasive;Modeling;Molecular;Molecular Weight;mouse model;multimodal data;Multivariate Analysis;Neoplasm Metastasis;new therapeutic target;nonalcoholic steatohepatitis;novel;novel marker;organ injury;Outcome;outcome prediction;Patient risk;Patient-Focused Outcomes;Patients;Peptide Fragments;Peptide Hydrolases;Peptide Synthesis;Peptides;Pharmacotherapy;Plasma;Population;post-transplant;predictive modeling;predictive tools;Predictive Value;Prevention;Production;profiles in patients;Prognosis;Prognostic Marker;prospective;Protease Inhibitor;Protein Fragment;Proteins;Recurrence;Risk;risk prediction;risk stratification;Role;Signal Transduction;simple steatosis;Steatohepatitis;targeted treatment;Testing;Time;Tissues;tool;Work

PROJECT_TITLE: Novel Biomarkers for Post-Liver Transplant NASH Fibrosis

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Aging;Neurodegenerative;Neurosciences

ORG_CITY: BATON ROUGE

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: LOUISIANA STATE UNIV A&M COL BATON ROUGE

ORG_STATE: LA

PHR: NARRATIVE Many hearing and language disorders arise from pathological alterations to the central auditory pathways. This study is relevant to public health since it will investigate the hitherto overlooked contralateral auditory tectothalamic pathways as a neural substrate in these disorders. Therefore, this research is relevant to part of NIH’s mission, since it develops the basic knowledge that will lead to improved methods for diagnosing, preventing, and treating auditory disorders associated with aging, development, trauma, and neurodegeneration.

PI_NAMEs: LEE, CHARLES C (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: Acoustics;Affect;Aging;Auditory;auditory pathway;auditory processing;auditory stimulus;Auditory system;auditory thalamus;Behavior;behavioral impairment;Bilateral;Binaural;Binding;Brain;Brain Stem;cell type;Cells;Central Auditory Processing Disorder;Contralateral;Development;Diagnosis;Diagnostic;diagnostic development;diagnostic strategy;Disease;Ear;Equilibrium;Esthesia;experience;experimental study;Failure;Future;Glutamates;Goals;Health;Hearing problem;Impaired cognition;Impairment;improved;In Vitro;in vivo;Inferior;Inferior Colliculus;information processing;Injections;innovation;Investigation;Ipsilateral;Knowledge;Language Disorders;Lasers;life span;Light;Link;Medial geniculate body;Mediating;Methods;Midbrain structure;Mission;Modernization;Mus;Nerve Degeneration;neural;neural circuit;Neuroanatomy;neuromechanism;Neurons;neurophysiology;normal hearing;optogenetics;Outcome;Pathologic;Pathway interactions;Pattern;Physiological;Population;Presbycusis;prevent;Preventive measure;Process;Productivity;Property;prospective;Public Health;Quality of life;Research;response;Role;Scanning;Scheme;Signal Transduction;Slice;Societies;sound;Source;source localization;Stimulus;Structure;Synapses;System;Techniques;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Tinnitus;Tracer;Trauma;United States National Institutes of Health;Viral

PROJECT_TITLE: Bilateral integration of the auditory scene

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Drug Abuse (NIDA only);Substance Misuse

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE The purpose of this application is to continue a highly successful training program of nearly 25 years in translational and interdisciplinary research on substance use disorders and offers research training on bio- behavioral factors in substance use disorders at the pre-doctoral and post-doctoral levels. Graduates of this program are actively involved in research, teaching, publishing articles, and becoming independent addiction researchers. We aim to continue this record of success in the next funding period because the need for a translational or interdisciplinary program is greater today than ever before, and the proposed training program fills a unique niche in substance use disorder research.

PI_NAMEs: RUSH, CRAIG R;STOOPS, WILLIAM WALTON (contact)

PROGRAM_OFFICER_NAME: KAUTZ, MARY A

PROJECT_TERMS: Behavior;Drug abuse;Research Training

PROJECT_TITLE: Research Training in Drug Abuse Behavior


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Postural Orthostatic Tachycardia Syndrome

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Postural Tachycardia Syndrome is a disabling condition that affects 3 million young people in the US. This project will test the novel idea that GIP, a hormone that is released after meals, contributes to the presyncopal symptoms, and increased upright heart rate in these patients. The results from these studies will inform the public on the cause and potential treatment for these symptoms.

PI_NAMEs: SHIBAO, CYNDYA ADRIANA (contact)

PROGRAM_OFFICER_NAME: SCHUM, PAULA

PROJECT_TERMS: Adult;Affect;Age;antagonist;arteriole;Blood;Blood flow;Blood Pressure;Blood Volume;Body mass index;C-Peptide;Canis familiaris;Carbohydrates;Cardiac Output;Chronic;Clinical;Communities;Consumption;Continuous Positive Airway Pressure;Cross-Over Studies;Data;Diet;Disabling condition;Disease;Dose;Double-Blind Method;Eating;Electric Capacitance;electric impedance;Endothelial Cells;Enrollment;Experimental Designs;falls;Fasting;Functional disorder;gastric inhibitory polypeptide receptor;Glucose;Goals;Head;Heart Rate;hemodynamics;Hormones;Human;Human body;improved;incretin hormone;Ingestion;innovation;insulin secretion;Intake;Intestines;Intravenous infusion procedures;Knowledge;Measures;Mesentery;novel;Oral;Orthostatic tachycardia;Patients;Peripheral Resistance;Persons;Physiological;Polypeptide Hormones;Positioning Attribute;positive airway pressure;Postprandial Period;Postural Orthostatic Tachycardia Syndrome;Posture;Property;Quality of life;Randomized;receptor;Research;response;Saline;Smooth Muscle Myocytes;Splanchnic Circulation;Stroke Volume;Superior mesenteric artery structure;Supination;Surveys;symptom treatment;Symptoms;Tachycardia;Techniques;Testing;Time;United States;Veins;Venous;young woman

PROJECT_TITLE: Mechanism of Glucose-dependent insulinotropic polypeptide (GIP) on Splanchnic Venous Capacitance in Postural Tachycardia Syndrome

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: ATLANTA

ORG_DEPT: ORTHOPEDICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: NARRATIVE Painful disc degeneration is a major public health concern with few minimally invasive and effective treatments available. This study identifies the role of the phosphatase PHLPP1 on nucleus pulposus tissue during disc degeneration and 1) investigates if PHLPP1 inhibition can delay disease progression via suppressing inflammation and matrix degradation using conditional Phlpp1 knockout mice and PHLPP1 gene knockdown in human nucleus pulposus cells, and 2) develops nanoformulations for controlled PHLPP inhibitor release into degenerated Wildtype mouse IVDs. This study addresses a highly significant clinical problem, identifies a novel mechanism for disc degeneration and investigates drug delivery vehicles for developing novel minimally invasive treatments.

PI_NAMEs: ILLIEN-JUNGER, SVENJA  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Acceleration;Address;Aftercare;Age;aged;Aging;Animal Model;Apoptosis;Back Pain;Biochemical;Biological;biomaterial compatibility;Biomechanics;bone;Cell Death Induction;Cell Proliferation;Cells;Cellularity;Chronic;Clinical;cytokine;Data;Deceleration;Degenerative polyarthritis;delivery vehicle;Deposition;Deterioration;Development;discogenic pain;Disease;Disease Progression;Drug Delivery Systems;Economic Burden;effective therapy;efficacy evaluation;efficacy testing;Ensure;Enzyme-Linked Immunosorbent Assay;Enzymes;experimental study;Extracellular Matrix;Extracellular Matrix Degradation;fetal;Formulation;Genes;Genotype;Glycosaminoglycans;Human;human tissue;improved;In Vitro;in vivo;Incubated;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;Injectable;Injections;innovation;insight;interest;Intervertebral disc structure;intervertebral disk degeneration;knock-down;Knock-out;Knockout Mice;Lead;leucine-rich repeat protein;loss of function;Macrophage;MAP Kinase Gene;MAPK Signaling Pathway Pathway;Methods;minimally invasive;Modality;Modeling;Molecular;mouse model;Mus;Musculoskeletal;mutant;nanocarrier;nanoformulation;nanolabel;nanoparticle;Nanotubes;Needles;neutrophil;novel;nucleus pulposus;old mice;Operative Surgical Procedures;Osteoclasts;Outcome Measure;Pain;pain relief;Pathway interactions;Pattern;PH Domain;Pharmaceutical Preparations;Phosphoric Monoester Hydrolases;Phosphorylation;PI3K/AKT;Play;prevent;Property;Protein Dephosphorylation;Protein phosphatase;Protein Phosphatase Inhibitor;protein phosphatase inhibitor-1;Proto-Oncogene Proteins c-akt;Public Health;Publications;Publishing;Repression;Research;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Small Interfering RNA;small molecule;small molecule inhibitor;socioeconomics;Suspensions;Testing;Therapeutic;Time;Tissues;transcriptome sequencing;translational study;Traumatic Arthropathy;United States;Western Blotting;Wild Type Mouse;Work

PROJECT_TITLE: Targeting PHLPP to treat interval disc degeneration using surgical and drug delivery methods

STUDY_SECTION: SBSR

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


NIH_SPENDING_CATS: Cancer;Cervical Cancer;Genetics;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human;Women's Health Research

ORG_CITY: CORAL GABLES

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative Beyond its role in noncoding RNA processing, we find Integrator, an RNA polymerase II- associated complex, regulates the 3’-end processing and termination of a set of protein coding genes. Unexpectedly, we further uncover a role for Integrator in regulation of NFκB signaling, a critical mediator of inflammatory response. Our studies will provide fundamental insight into regulation of gene expression, which will be the basis for development of rational therapies against pathogenic gene expression.

PI_NAMEs: SHIEKHATTAR, RAMIN  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Affinity Chromatography;Antibodies;Architecture;Atrophic;B-Cell Activation;Biogenesis;Biological Process;Bone Marrow;BRCA1 gene;C-terminal;cancer cell;Catalytic Domain;Catalytic RNA;Cell Differentiation process;Cells;Chromatin;chromatin immunoprecipitation;Cleavage And Polyadenylation Specificity Factor;Code;Complex;conditional knockout;Development;Disease;embryonic stem cell;Endoribonucleases;Enhancers;Enzymes;Epigenetic Process;Focal Seizure;Funding;Gene Expression;Gene Expression Regulation;Genes;Genetic Enhancer Element;Genetic Transcription;Genomics;Grant;Growth Factor;Hour;Human;human disease;Immediate-Early Genes;Immune system;inducible Cre;Inflammation Mediators;Inflammatory;Inflammatory Response;insight;Knockout Mice;Lead;Light;Macrophage;Malignant neoplasm of cervix uteri;Mass Spectrum Analysis;Messenger RNA;Mouse Embryonic Stem Cells;Multiprotein Complexes;Mutate;Mutation;neonate;Neurodevelopmental Disorder;NF-kappa B;Nuclear;p65;Pathway interactions;Play;pluripotency;programs;promoter;Proteins;Proteomics;Regulation;RELA gene;response;RNA;RNA Polymerase II;RNA Processing;Role;Seizures;self-renewal;Set protein;Signal Transduction;Site;Small Nuclear RNA;Spliceosomes;stable cell line;Stress;Syndrome;System;Testing;Time;TNF gene;Transcription Elongation;transcription factor;Transcription Factor AP-1;Transcriptional Regulation;Untranslated RNA;virulence gene

PROJECT_TITLE: Elucidation of Integrator's Function

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Hematology;Immunotherapy;Patient Safety;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative The proposed study is a multi-center phase III trial that compares the percentage of newly diagnosed SAA patients with immune suppression-free survival with adequate counts (ISFS-AC) at 2-years between those randomized to Immune Suppression Therapy (IST) vs 9-10/10 HLA matched unrelated donor (URD) bone marrow transplant (BMT). The study will also address patient-reported outcomes and markers of fertility in each arm and explore critical biological correlates including assessing for germline genetic mutations associated with pediatric SAA that may affect response to BMT or IST and the development of clonal hematopoiesis following IST vs BMT. The study would represent the largest randomized study in pediatric SAA ever attempted with the goal of providing practice-altering conclusions to the field.

PI_NAMEs: PULSIPHER, MICHAEL A;WILLIAMS, DAVID A (contact)

PROGRAM_OFFICER_NAME: HAILU, BENYAM

PROJECT_TERMS: Address;Adult;Adverse event;Affect;Age;American;Aplastic Anemia;arm;autoimmune pathogenesis;Biological;Blood;Bone marrow failure;Bone Marrow Transplantation;Cell Therapy;Child;Childhood;Clinical;cohort;Collaborations;Consensus;Cyclophosphamide;Cyclosporine;Cyclosporins;cytopenia;Data;Development;Disease;Disease-Free Survival;DNA Sequence Alteration;Donor Selection;Dose;Equus caballus;Failure;Fertility;fertility preservation;fludarabine;Funding;Genetic;Germ Lines;Goals;graft failure;graft vs host disease;health assessment;health related quality of life;Hematology;Hematopoiesis;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;HLA Antigens;human leukocyte antigen testing;Immune;Immunosuppression;improved;In complete remission;Incidence;Institution;international center;Malignant Neoplasms;Marrow;Mind;Molecular;mortality;Movement;National Heart, Lung, and Blood Institute;Newly Diagnosed;North America;novel therapeutic intervention;Oryctolagus cuniculus;Outcome;Patient Outcomes Assessments;Patients;Pediatric cohort;pediatric patients;Phase;phase change;phase III trial;pilot trial;Publishing;Quality of life;Randomized;randomized trial;Recommendation;Relapse;Reporting;Research;response;Risk;safety and feasibility;Siblings;standard of care;Survival Rate;Time;transplantation therapy;trial comparing;United States National Institutes of Health;Whole-Body Irradiation;young adult

PROJECT_TITLE: A Phase III Randomized Trial Comparing Unrelated Donor Bone Marrow Transplantation with Immune Suppressive Therapy for Newly Diagnosed Pediatric and Young Adult Patients with Severe Aplastic Anemia


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Hematology;Infectious Diseases;Kidney Disease;Patient Safety;Prevention;Sepsis

PHR: PROJECT NARRATIVE Acute kidney injury (AKI) is an independent risk factor for death that affects 10-15% of hospitalized patients and more than 50% of patients admitted to the intensive care unit. Sepsis is the most frequent cause of AKI, affecting 48 million people worldwide every year, and accounting for approximately 11 million of annual global deaths. Despite these figures, there are no known therapies to prevent or reverse septic AKI; hence this study aims to establish the safety and feasibility of the implementation of metformin in the treatment of AKI in patients with sepsis.

PI_NAMEs: GOMEZ DANIES, HERNANDO  (contact)

PROGRAM_OFFICER_NAME: SCHULMAN, IVONNE HERNANDEZ

PROJECT_TERMS: 5'-AMP-activated protein kinase;Accounting;Acute Renal Failure with Renal Papillary Necrosis;Address;Adherence;Adult;Affect;Agreement;arm;Biological;Biological Markers;Blood Platelets;Cardiac;Cellular Metabolic Process;Cessation of life;Clinical Trials Design;Consensus;Consent;Control Groups;Data;design;Development;diabetic patient;Diagnosis;Dose;Drops;Drug Kinetics;Effectiveness;efficacy evaluation;efficacy trial;energy balance;Enteral;Exposure to;extracellular;Feasibility Studies;Feedback;follow-up;Functional disorder;Funding;Future;gastrointestinal;Goals;Heterogeneity;Hospitalization;Human;Hypoglycemia;Immune;Immune response;improved;Infection;Injury to Kidney;Intensive Care Units;International;Intervention;Kidney;Knowledge;Life;Meta-Analysis;Metabolic acidosis;Metformin;Mitochondria;mitochondrial dysfunction;Mitochondrial Electron Transport Complex I;mitochondrial metabolism;mortality;mortality risk;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Observational Study;Oral;Organ;organ injury;Outcome;Pathway interactions;Patient Admission;patient screening;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Physicians;Placebo Control;Placebos;Predisposition;prevent;protective effect;Protocols documentation;Randomized;randomized, clinical trials;Recommendation;Recovery;recruit;Regimen;Reporting;Respiration;Retrospective Studies;Risk Factors;Safety;safety and feasibility;safety assessment;Sepsis;septic;Septic Shock;Serious Adverse Event;Stress;therapeutic candidate;TIMP2 gene;Traumatic Brain Injury;treatment arm;treatment strategy;urinary;Western Blotting

PROJECT_TITLE: A Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis induced AKI (LiMiT AKI)

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

PHR: PROJECT NARRATIVE Parkinson’s Disease (PD) is the second most common neurodegenerative disease, affecting nearly one million Americans and ten million people worldwide. This proposal aims to understand how the LRRK2 kinase, mutation of which is the most common genetic cause of PD, works at the molecular level. We believe that the outcomes of our research will provide the conceptual framework for novel drug discovery strategies to combat PD.

PI_NAMEs: LEE, CHIA-HSUEH  (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Accounting;Address;Affect;AGFG1 gene;Aging;American;Architecture;Biochemical;Biological Assay;Biophysics;Cells;Cellular Assay;Cellular biology;combat;Complex;Cryoelectron Microscopy;Data;design;Development;Disease;DNA Sequence Alteration;drug development;drug discovery;experience;Family;Foundations;gain of function mutation;Genes;Genetic;Guanosine Triphosphate Phosphohydrolases;Histologic;Human;Idiopathic Parkinson Disease;Image;In Vitro;inhibitor;Knockout Mice;Knowledge;Lead;Length;LRRK2 gene;Lysosomes;Membrane;Molecular;Molecular Conformation;Monomeric GTP-Binding Proteins;Movement Disorders;Mutagenesis;Mutation;Neurodegenerative Disorders;novel;novel strategies;novel therapeutics;Outcome;Parkinson Disease;particle;Persons;Pharmacologic Substance;Phenotype;Phosphorylation;Phosphotransferases;Play;Process;Proteins;rab GTP-Binding Proteins;reconstitution;recruit;Research;Risk Factors;risk variant;Role;sporadic Parkinson's Disease;structural biology;Structure;Substrate Specificity;Techniques;Tertiary Protein Structure;trans-Golgi Network;vesicle transport;Work

PROJECT_TITLE: Structural analysis of the human LRRK2

STUDY_SECTION: MSFC

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


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

ORG_CITY: IRVINE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE The integration of sensory and cognitive information streams is critical for complex behaviors. While the breakdown of this interaction is thought to underpin numerous neuropsychiatric disorders, our understanding of how individual neurons combine sensory signals with cognitive inputs remains limited. Here, we propose a comprehensive experimental and computational approach to determine the principles guiding pathway integration in individual neurons, establishing the foundation for future basic and translational research.

PI_NAMEs: LUR, GYORGY  (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Action Potentials;Afferent Pathways;Attention;Basic Science;Behavior;Behavioral;Brain;Cell Physiology;cell type;Cells;Cognitive;cognitive process;Color;Complex;Computer Models;Computing Methodologies;Data;Decision Making;Dependence;designer receptors exclusively activated by designer drugs;Distant;Electrophysiology (science);Exhibits;expectation;experimental study;Feedback;Foundations;Future;Genetic;Goals;hippocampal pyramidal neuron;Human;Impairment;in vivo;Individual;information processing;insight;Knowledge;Measures;Memory;multimodality;multisensory;N-Methylaspartate;Neocortex;nerve supply;neural;neuronal circuitry;Neurons;neuropsychiatric disorder;novel;optogenetics;Outcome;Output;Parietal Lobe;Pathway interactions;Pharmacology;Play;Population;predictive modeling;Primates;Research;response;Rodent;Role;Sensory;sensory feedback;sensory input;sensory integration;Short-Term Memory;Signal Transduction;Slice;Source;Specificity;Stream;Sum;superior colliculus Corpora quadrigemina;Synapses;Testing;Translational Research;Work

PROJECT_TITLE: Feedforward-feedback integration in the posterior parietal cortex

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences

ORG_DEPT: BIOLOGY

PHR: PROJECT NARRATIVE Intellectual disability, characterized by an I.Q. less than 70 and significant impairments in intellectual and adaptive behavior, affects approximately 1-3% of the world population. Despite the heterogeneous and genetically complex nature, recent studies have led to the discovery that many genes linked to intellectual disability converge on a limited set of molecular pathways, suggesting that distinct intellectual disabilities are unified by common underlying molecular dysfunctions. Here we utilize the fruit fly Drosophila as a system to model a heritable form of intellectual disability by exploring the intersection of specific factors and RNA modifications to define molecular mechanisms underlying intellectual disability disease pathogenesis.

PI_NAMEs: LANCASTER, CARLY L (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Adaptive Behaviors;Adult;Affect;Alternative Splicing;analog;Axon;axon guidance;Binding;Biochemical;Brain;brain dysfunction;brain morphology;career development;Cells;Clinical;clinical heterogeneity;Complex;Defect;Deposition;Development;Diagnosis;Disease;disease heterogeneity;Drosophila genus;Drosophila melanogaster;epitranscriptomics;Etiology;Event;experience;Functional disorder;Gene Expression Regulation;Genes;Genetic;Genetic Techniques;Guanine Nucleotide Exchange Factors;Heritability;Hippocampus;Human;Hypermethylation;Impairment;Individual;Inherited;inhibitor;insight;Intellectual functioning disability;Introns;Lesion;life time cost;Link;Locomotion;loss of function mutation;Mediating;Memory;Mentors;Messenger RNA;Methyltransferase;model organism;Modeling;Modification;Molecular;Morphology;Mushroom Bodies;Mutate;Mutation;Nature;Nervous System;neurodevelopment;Neurodevelopmental Disorder;Neurologic;neuron development;Neuronal Differentiation;Neurons;novel;Nuclear;Orthologous Gene;Pathogenesis;Pathway interactions;Patients;Play;Poly(A)+ RNA;Population;Post-Transcriptional Regulation;posttranscriptional;protein expression;protein function;Protein Isoforms;Proteins;Regulation;Research Project Grants;rho;RNA;RNA Splicing;RNA, Messenger, Splicing;RNA-Binding Proteins;Role;spatiotemporal;Synaptic plasticity;System;Testing;Tissues;Training;Transcript;transcriptome;transcriptome sequencing;TRIO gene;Vertebrates;Work;Zinc Fingers

PROJECT_TITLE: A Conserved RNA Binding Protein Regulates RNAs Critical for Neurodevelopment


ORG_CITY: LA JOLLA

ORG_NAME: LA JOLLA INSTITUTE FOR IMMUNOLOGY

PHR: Narrative T cells are a class of immune cells that fight diseases and cancer, whereas regulatory T cells (Tregs) are an opposing class that are essential to prevent autoimmune disease and rejection of organ or bone marrow transplants. Our project aims to understand how DNA methylation and demethylation affect T cell expansion and regulatory T cell function. This may give us new methods for improving how T cells and regulatory T cells function in the body to improve the efficacy of patient treatment.

PI_NAMEs: RAO, ANJANA  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: Adoptive Transfer;Affect;Aging;alpha ketoglutarate;Aneuploidy;Antigens;Architecture;Autoimmune;Autoimmune Diseases;Biochemical;Bone Marrow;Bone Marrow Transplantation;cancer cell;Cardiovascular Diseases;CD19 gene;CD4 Positive T Lymphocytes;Cell Culture System;Cell Lineage;Cell Physiology;cell type;Cells;Chimera organism;Chromosomal Instability;Chromosome 17;chromosome missegregation;congenic;cytokine;Cytosine;Data;demethylation;Development;Dioxygenases;Disease;DNA;DNA Damage;DNA Methylation;DNA Modification Methylases;DNA Structure;DNA Transposable Elements;Enhancers;Enterobacteria phage P1 Cre recombinase;Enzymes;experimental study;Female;fighting;FOXP3 gene;Functional disorder;G-Quartets;Genes;Genome;genome-wide;Hematopoiesis;Hematopoietic;Hematopoietic Neoplasms;Heterochromatin;Heterozygote;Histones;Human;IL17 gene;Immune;Immunocompetent;Impairment;improved;In Vitro;in vivo;Inflammation;Inflammatory;innate immune sensing;Interferon Type I;Interferons;Interleukin-6;Iron;Link;LoxP-flanked allele;Lymphocytic Infiltrate;Lysine;Malignant Neoplasms;Methods;methyl group;Methylation;methylation pattern;micronucleus;Molecular;Mouse Strains;Mus;Mutant Strains Mice;Mutation;Myelogenous;Neurodegenerative Disorders;Older Population;Oncogenic;Organ;organ transplant rejection;Outcome;Oxygen;Paper;Pathway interactions;Patients;Penetrance;Phenotype;premalignant;prevent;promoter;Proteins;Recurrence;Regulatory T-Lymphocyte;Repetitive Sequence;Reporting;response;RNA;Role;Signal Transduction;Solid;Specific qualifier value;stem;Sterility;Structure;Syndrome;System;systemic inflammatory response;Systemic Lupus Erythematosus;T-Cell Receptor;T-Lymphocyte;Testing;Tetanus Helper Peptide;Trisomy 17;Up-Regulation;whole genome;X Chromosome;X Inactivation

PROJECT_TITLE: Investigating the role of TET deficiency in promoting T cell expansion and inflammation

STUDY_SECTION: CMIA

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


NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Inflammatory Bowel Disease

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: The proposed research is relevant to public health as inflammation has long been considered to play a causative role in colon cancer development and druggable targets involved, however, remain largely unknown. This application will test the hypothesis that p38 MAPK activation converts inflammation responses to colon tumorigenesis. Thus, by demonstrating the essential role of p38 in intestinal tumorigenesis in mouse models and the therapeutic activity of its pharmacological inhibitor pirfenidone, the proposed research is highly relevant to the NIH’s mission of extending healthy life and reducing the burdens of illness.

PI_NAMEs: CHEN, GUAN  (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: antagonist;Anti-Inflammatory Agents;APC gene;Attenuated;Azoxymethane;burden of illness;c-myc Genes;cancer cell;Carcinoma;Cessation of life;chemotherapy;Clinical;cofactor;Colitis;colitis associated cancer;Collaborations;Colon Carcinoma;colon tumorigenesis;Colorectal Cancer;Complex;cytokine;Development;dextran sulfate sodium induced colitis;DNA;driving force;druggable target;Effectiveness;Epithelial Cells;Epithelium;Fluorouracil;Genetic;Genetic Transcription;Growth;Growth and Development function;Human;In Vitro;in vivo;Inflammation;Inflammatory;inhibitor;Interleukin-10;intestinal epithelium;intestinal tumorigenesis;Intestines;Knock-out;Knockout Mice;Leucocytic infiltrate;Life;Malignant - descriptor;MAP Kinase Gene;MAPK12 gene;member;Mission;mouse model;multicatalytic endopeptidase complex;murine colitis;Mus;Mutant Strains Mice;novel;novel strategies;Nuclear Translocation;Oncogenic;overexpression;p38 Mitogen Activated Protein Kinase;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phosphorylation;Phosphotransferases;Pirfenidone;Play;promoter;Public Health;Research;response;Role;Severities;Signal Transduction;Sodium Dextran Sulfate;Specimen;Spontaneous colitis;Suppressor Mutations;targeted cancer therapy;targeted treatment;TCF7L2 gene;Testing;Therapeutic;Therapeutic Intervention;Tissues;tumorigenesis;United States National Institutes of Health;Wild Type Mouse;WNT Signaling Pathway;Xenograft procedure

PROJECT_TITLE: p38gamma MAPK signaling promotes intestinal tumorigenesis

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Project Narrative This work seeks to define the role of developmental context in oncohistone-mediated glioma initiation and maintenance using a novel inducible transgenic cerebral organoid system. The overall approach is to alter the timing and sequence of oncogene induction during human cerebral organoid development, interrogate the functional consequences at single cell resolution, and evaluate the impact on tumor phenotype and maintenance. The long-term goal of this research program is to identify better therapeutic targets for oncohistone-driven pediatric high-grade gliomas, one of the most lethal childhood cancers.

PI_NAMEs: GRAHAM, MAYA SRIKANTH (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: 3-Dimensional;Address;Adult;Advisory Committees;Area;Automobile Driving;Bioinformatics;Biological Models;Biology;Biomedical Research;Brain;Brain Neoplasms;Cancer Etiology;career;career development;Cell Lineage;Cell Separation;Cells;Cerebrum;childhood cancer mortality;Childhood Glioma;Chromatin;chromatin remodeling;Chronology;Clinical;Clinical Trials;Collaborations;Competence;constitutive expression;Data;Development;Development Plans;DNA methylation profiling;Dominant-Negative Mutation;Doxycycline;effective therapy;Engineering;Environment;Epigenetic Process;epigenetic regulation;Event;experience;gene induction;Genetic;Glioma;Gliomagenesis;Goals;Histology;Histone H3;Histones;Human;human stem cells;In Vitro;in vivo;induced pluripotent stem cell;inhibitor;innovation;insight;instructor;Knowledge;Maintenance;Malignant - descriptor;Malignant Childhood Neoplasm;Malignant Glioma;Mediating;Memorial Sloan-Kettering Cancer Center;Mentors;Mentorship;Mesenchymal;Mission;Modeling;Molecular;mutant;Mutation;National Institute of Neurological Disorders and Stroke;nerve stem cell;neural;neuro-oncology;neurodevelopment;Neurons;novel;Oncogenes;oncohistone;Organoids;Pathogenesis;Patients;PDGFRA gene;pharmacologic;Phenotype;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;programs;promoter;Qualifying;Regulation;Research;Research Personnel;Resolution;Resources;Role;screening;Side;Signal Transduction;single-cell RNA sequencing;skills;stem cell population;System;targeted treatment;Techniques;Therapeutic;therapeutic development;therapeutic target;TP53 gene;Training;transcriptome sequencing;transgene expression;Transgenes;Transgenic Mice;Transgenic Organisms;Translating;translational oncology;tumor;tumor initiation;Variant;Work

PROJECT_TITLE: Defining the Role of Developmental Context in Oncohistone-Driven Gliomagenesis

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative While all cells contain the same genetic information, control of gene expression is crucial for defining unique cell types. The nuclear lamina contributes to gene repression by compacting and repressing approximately one third of the genome in heterochromatin at the nuclear periphery, yet it remains a mystery how association with the nuclear lamina confers repression. The overarching goal of my research program is to resolve this mystery by defining how components of the lamina and chromatin communicate to mediate gene repression.

PI_NAMEs: BUCHWALTER, ABIGAIL LYNN (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Acute;Binding;Biological Assay;Cell Physiology;cell type;Cells;Chromatin;chromatin modification;Communication;Complex;Elements;Euchromatin;Gene Abnormality;Gene Expression;gene repression;Genes;genetic information;Genetic Transcription;Genome;genome integrity;genomic locus;Goals;Heterochromatin;Histone H3;histone modification;human disease;In Vitro;lamin B receptor;Lamin Type A;Lamins;Link;Lysine;Mammalian Cell;Mediating;Membrane Proteins;Methyltransferase;Modeling;Modification;Mutation;Nuclear;Nuclear Inner Membrane;Nuclear Lamina;Nucleosomes;Peripheral;programs;Proteins;Repression;Reproducibility;Research;residence;Signal Transduction;Specific qualifier value;Structure;Syndrome;time use;Work

PROJECT_TITLE: Understanding mechanisms of heterochromatin tethering at the nuclear lamina

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


ADMINISTERING_IC: HD

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

PHR: Narrative The goal of this renewal application is to continue Vanderbilt Department of Pediatrics mentored training program for early career pediatricians possessing both the aptitude and passion to become a new generation of basic and translational physician scientists. We will focus on career development areas where Vanderbilt has internationally recognized programs of discovery combined with a record of sustained excellence in research mentorship. Each pediatric K12 scholar will have an individualized training program developed by the PI and Training Directors in collaboration with a multidisciplinary mentorship team, and will be supported by a broad array of institutional and departmental resources.

PI_NAMEs: DEBAUN, MICHAEL R. (contact)

PROGRAM_OFFICER_NAME: WINER, KAREN

PROJECT_TERMS: Academic Medical Centers;Aptitude;Area;Cancer Biology;cardiogenesis;career;career development;Childhood;Collaborations;collaborative environment;Communicable Diseases;Core Facility;Coupled;Diabetes Mellitus;Disease;distraction;Elements;emerging pathogen;Environment;Evaluation;Faculty;Funding;Future;Genetic Medicine;Genomic medicine;Goals;Grant;Group Meetings;Health system;Heart Diseases;Hospitals;Institution;International;laboratory facility;Leadership;lung development;Lung Diseases;medical schools;meetings;Mentored Clinical Scientist Development Program;Mentors;Mentorship;Metabolism;Molecular;multidisciplinary;Nervous System Disorder;next generation;novel vaccines;Obesity;Pathogenesis;pediatric department;pediatrician;Physicians;Positioning Attribute;programs;Research;research and development;research facility;Research Personnel;Research Project Grants;Resources;Scientist;targeted treatment;therapeutic target;therapeutic vaccine;Time;Training;training opportunity;Training Programs;translational physician;Underrepresented Minority;United States National Institutes of Health

PROJECT_TITLE: Pathogenesis, Targeted Therapeutics, and New Vaccines for Childhood Disease


NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Brain Disorders;Drug Abuse (NIDA only);Genetics;Opioids;Pain Research;Substance Misuse

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: PROJECT NARRATIVE More than 76 million Americans use opioid drugs as analgesics for the treatment of long-term pain, and more than 2 million Americans now have opioid use disorders. This research program will study genetic and molecular mechanisms with important implications for treatment of chronic pain and management of problematic opioid side effects, such as tolerance, addiction and withdrawal. Thus, this project has long-term potential to contribute significantly to managing several major medical problems.

PI_NAMEs: GRILL, BROCK  (contact);ZHENG, NING

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: 26S proteasome;Acute;addiction;Affect;Affinity Chromatography;American;Analgesics;Animals;Behavior;Behavioral;Behavioral Genetics;Behavioral Model;behavioral response;behavioral tolerance;Binding;Binding Proteins;Biochemical;Biochemistry;Biological Assay;Biology;Caenorhabditis elegans;Cells;chronic pain management;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR/Cas technology;Dependence;desensitization;Development;Disease;drug action;Engineering;Exhibits;experimental study;Fentanyl;forward genetics;G-Protein-Coupled Receptors;Genes;Genetic;Genetic study;genome sequencing;Goals;GTP-Binding Proteins;high throughput screening;high-throughput drug screening;Human;Impairment;in vivo;inhibitor;innovation;Lesion;Mediating;Medical;Modeling;Molecular;Morphine;multicatalytic endopeptidase complex;mutant;Mutation;Nematoda;Nervous System;Nervous System Physiology;novel;opiate tolerance;Opioid;Opioid Analgesics;opioid exposure;Opioid Receptor;opioid use;opioid use disorder;Organism;Orphan;Orthologous Gene;Outcome;Pain;Pain management;Pathway interactions;Peripheral;Pharmaceutical Preparations;Pharmacology;prevent;programs;Proteomics;Regulation;Research;response;Rewards;Rodent;Role;screening;Shapes;side effect;Signal Transduction;Signaling Molecule;small molecule;small molecule inhibitor;System;targeted treatment;Testing;Time;Transgenic Organisms;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitination;Validation;whole genome;Withdrawal

PROJECT_TITLE: Regulation of Opioid Sensitivity and Tolerance by Ubiquitin Ligase Signaling


NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Project Narrative – PI: C. Mac Donald – EVOLVE-10 Study The overall goal is to investigate long-term advanced MR imaging measures and clinical outcome of concussive traumatic brain injury (TBI) sustained during deployment in US military personnel. We will relate these findings to prospectively acquired longitudinal imaging and clinical data from the acute/sub-acute, and early chronic stages following combat concussion collected on these patients as part of previous collaborative efforts. We hypothesize that early clinical and imaging measures can be used to predict high risk vs. low risk for poor 10-year outcome which will offer important insight into the long-term impact of war-time mild TBI thereby guiding new recommendations for clinical management and therapeutic intervention.

PI_NAMEs: MACDONALD, CHRISTINE L (contact)

PROGRAM_OFFICER_NAME: UMOH, NSINI ALEASE

PROJECT_TERMS: active duty;Acute;Afghanistan;aging brain;Anatomy;Brain;Brain Concussion;brain control;Brain Injuries;Chronic;Clinical;Clinical assessments;Clinical Data;Clinical Management;clinical outcome measures;clinical predictors;cognitive function;cohort;combat;Data;Diffusion Magnetic Resonance Imaging;Enrollment;Evaluation;Evolution;Exposure to;Germany;Goals;Growth;high risk;Image;Image Analysis;injured;Injury;insight;Journals;Link;Long-Term Effects;Longitudinal Studies;Longitudinal, observational study;Magnetic Resonance Imaging;Measures;Medical;Medicine;men;Mental Health;mild traumatic brain injury;Military Personnel;Modeling;Neurobehavioral Manifestations;neuroimaging;Neurologic;Neurology;Neuropsychology;New England;Outcome;Patient Self-Report;Patients;Population;prospective;Prospective Studies;Publications;Recommendation;Recovery;Reporting;research clinical testing;resilience;Resolution;Risk;screening;Screening procedure;serial imaging;service member;Services;Subgroup;Symptoms;targeted treatment;Therapeutic Intervention;Time;Traumatic Brain Injury;Veterans;Woman

PROJECT_TITLE: EValuation Of Longitudinal outcomes in mild TBI Active-Duty Military and VEterans 10-Year

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Pediatric

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: Narrative The studies proposed in this application are focused on typical language development in infants and toddlers. The studies will measure infants’ use of statistical regularities in language input during predictive language processing, error-based learning, and infant-controlled exploration. The results will inform subsequent studies of children at risk for atypical language development, which is a significant public health concern, with the goal of promoting positive language acquisition outcomes.

PI_NAMEs: SAFFRAN, JENNY R. (contact)

PROGRAM_OFFICER_NAME: SALO, VIRGINIA CHARLOTTE

PROJECT_TERMS: adjudication;Adult;Attention;autism spectrum disorder;Behavior;behavior measurement;behavior prediction;Brain;Categories;Child;Cues;Data;data integration;Development;Developmental Disabilities;Environment;experimental study;Exploratory Behavior;Eye Movements;Failure;Future;Goals;Human Development;improved;Individual Differences;Infant;information seeking behavior;Intervention;Investigation;Knowledge;Label;Language;Language Delays;Language Development;language processing;Learning;learning strategy;Linguistics;Literature;Maps;Measures;Outcome;Outcome Study;Paper;Participant;Pattern;Probability;Process;processing speed;Public Health;Research;Research Design;Risk;Role;Sampling;Shapes;skills;Source;statistical learning;statistics;Structure;syntax;Task Performances;Testing;theories;Time;Toddler;Uncertainty;Update;visual tracking;word learning;Writing

PROJECT_TITLE: Statistical Learning in Infant Language Acquisition


ORG_CITY: RICHARDSON

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: Narrative The proposed work aims at developing new methods for selective and efficient conversion of simple and abundant molecules into functionalized compounds of biological importance, as well as late-stage functionalization of complex molecules and drugs. The proposed approaches rely on employment of hybrid transition metal-catalyzed radical methodologies, including desaturation, atom transfer, cross-coupling, and cascade functionalization techniques. If fully developed, these methods would dramatically broaden the arsenal of synthetic tools available for medicinal chemists and biologists, and will most certainly impact drug discovery research and related health-oriented sciences.

PI_NAMEs: GEVORGYAN, VLADIMIR  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Transition Metal-Radical Hybrid Methods for Organic Synthesis

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative Chemotactic behaviors influence the environmental distributions of motile microorganisms, the compositions of microbial communities such as biofilms, and host invasion during the establishment of beneficial symbioses and harmful infections. Better understanding of the molecular mechanisms of stimulus detection and sensory signaling by bacterial chemoreceptors should lead to new strategies for augmenting the beneficial behaviors of bacteria and to new therapies for harmful bacterial infections.

PI_NAMEs: PARKINSON, JOHN S (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Bacteria;Bacterial Infections;Behavior;behavior influence;Binding;Biological Assay;Biological Models;Catalytic Domain;Cell membrane;Cells;Chemicals;Chemoreceptors;Chemotaxis;Collaborations;Communication;Communities;Complex;Coupled;Couples;crosslink;Cryoelectron Microscopy;Cytoplasm;Cytoplasmic Protein;Cytoplasmic Receptors;Detection;Development;Devices;Distal;Dose;Elements;Environment;Escherichia coli;Feedback;flexibility;Fluorescence Resonance Energy Transfer;Glycine;Goals;Histidine;host colonization;Image Enhancement;imaging study;improved;in vivo;Infection;Invaded;Life Cycle Stages;Ligand Binding Domain;Ligands;Mediating;Membrane;Methylation;Microbe;microbial;Microbial Biofilms;microbial community;microbial composition;microorganism;Modeling;Molecular;Molecular Conformation;molecular dynamics;Molecular Genetics;Monitor;Motility;Motion;Motor;Movement;mutant;novel therapeutic intervention;novel therapeutics;OmpR protein;Organism;Output;Phase;Phosphotransferases;Play;prevent;Property;protein crosslink;receptor;Receptor Signaling;Resolution;response;Role;Rotation;Scaffolding Protein;Sensory;Sensory Process;Serine;Signal Transduction;Signaling Protein;Stimulus;Structure;Stuttering;Symbiosis;Testing;transmission process;Work

PROJECT_TITLE: Intracellular Signaling by Bacterial Chemoreceptors

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


NIH_SPENDING_CATS: Clinical Research;Immunization;Infectious Diseases;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Vaccine Related

PHR: PROJECT NARRATIVE Understanding hemolytic lipid mediated toxicity and evaluation of compounds that can inhibit its function is valuable for prevention of Group B Streptococcal infections in humans and is relevant to other microbial lipid toxins.

PI_NAMEs: RAJAGOPAL, LAKSHMI  (contact)

PROGRAM_OFFICER_NAME: GU, XIN-XING

PROJECT_TERMS: Adult;adverse outcome;analog;Antibodies;Antibody Formation;Applications Grants;Area;aspirate;Attenuated;B-Lymphocytes;Bacillus cereus;Bacteria;Bacterial Infections;Bacteroides;Biological;Cell surface;Cells;Cerebral Palsy;chemical synthesis;Clinical;cytotoxic;Cytotoxin;diabetic;Disease;Elderly;Erythrocytes;Evaluation;experimental study;Genes;Genus Mycobacterium;Gram-Positive Bacteria;Group Structure;Hemolysin;Hemolysis;Human;human morbidity;human mortality;Immune;Immune Sera;Immunity;Immunization;Immunocompromised Host;immunogenicity;improved;in utero;in vivo;in vivo Model;Infection;inhibiting antibody;Injury;Integration Host Factors;Intellectual functioning disability;Lipids;Macrophage;mast cell;Mediating;Membrane;Meningitis;Microbe;microbial;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Names;Neonatal;neonatal lung injury;Neurologic;neutrophil;Newborn Infant;Ornithine;pathogen;Pathogenesis;Pathology;Perinatal;Pigments;Placenta;Pneumonia;Pregnancy;pregnant;Premature Birth;prevent;Prevention;Propionibacterium;Proteins;Pseudomonas;Public Health;Reporting;reproductive tract;Research;rhamnolipid;screening;Seizures;Sepsis;stillbirth;streptococcal group B hemolysin;Streptococcal Infections;Streptococcus Group B;T-Lymphocyte;Toxic effect;Toxin;Umbilical Cord Blood;Vaccinated;Vaccination;vaccine candidate;vaccine response;Vaccines;vaginal fluid;Vesicle;Virulence Factors;Woman;Work

PROJECT_TITLE: Neutralizing the GBS hemolytic lipid toxin


ORG_CITY: SYRACUSE

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

PHR: An increasing number of dominant mutations are found in adenine nucleotide translocase 1 (Ant1) to cause multi-systemic neural and muscular degeneration, but the underlying mechanism is poorly understood. We generated mouse models to test the hypothesis that the pathogenic variants of Ant1 affect mitochondrial protein import and cause mitochondrial Precursor Over- accumulation Stress (mPOS) in the cytosol. The studies may uncover protein import stress and mPOS as novel mechanisms of neural and muscular degeneration, and help the understanding and treatment of Ant1-induced diseases and possibly, many other clinical conditions that directly or indirectly affect mitochondrial protein import.

PI_NAMEs: CHEN, XIN JIE  (contact);MASSA, PAUL T;MIDDLETON, FRANK A.

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Address;Adenine Nucleotide Translocase;Affect;Aging;Amyotrophic Lateral Sclerosis;Animals;Area;Autophagocytosis;Behavioral;Bioenergetics;Cause of Death;Cell Death;Cell Death Induction;Cells;Central Nervous System;cerebral atrophy;Charge;Child;Chronic progressive external ophthalmoplegia;Clinical;Cytoprotection;Cytosol;Data;Defect;Degenerative Disorder;Dementia;Disease;dominant genetic mutation;Equilibrium;Experimental Models;FRAP1 gene;Frontotemporal Dementia;Functional disorder;Future;Gene Expression Profile;Genes;Genetic Transcription;Goals;hearing impairment;Heart;Histologic;Human;Impairment;Inner mitochondrial membrane;insight;Intervention;Knock-in Mouse;Late-Onset Disorder;Lateral;Maintenance;Membrane;Missense Mutation;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial dysfunction;Mitochondrial Proteins;Modeling;Molecular;mouse model;Mus;Muscle;muscle form;Muscle Weakness;mutant;Mutation;Myopathy;Names;neural;neuromechanism;neuromuscular;Neuromuscular Diseases;Neurons;novel;Nuclear;Nucleotides;old mice;Oxidative Phosphorylation;Oxidative Phosphorylation Deficiency;Oxidative Stress;Parkinson Disease;Pathogenicity;Pathology;Pathway interactions;Peripheral Nervous System Diseases;Phenotype;Play;posttranscriptional;preference;Protein Import;Protein Isoforms;Proteins;psychiatric symptom;receptor;Repression;Research;Respiration;Role;Seizures;Skeletal Muscle;SLC25A4 gene;Spastic Paraplegia;Spinocerebellar Ataxias;Stress;success;Suppressor-Effector T-Lymphocytes;Surface;Syndrome;System;Testing;tool;translocase;ubiquitin-protein ligase;Ubiquitination;Validation;Variant;Yeasts;young adult

PROJECT_TITLE: Novel mechanism of neural and muscular degeneration

STUDY_SECTION: CMAD

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


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Prevention

PHR: NARRATIVE In this application to address the global epidemic of cardiometabolic disease, the University of Washington (UW) Department of Global Health (DGH) is partnering with two long-standing collaborators, Kathmandu University (KU) and University of Nairobi (UON), to facilitate cross-cultural training experiences for building future research opportunities. As a part of this training, we will support 6 students to complete MPH degrees at UW, 5 students to complete MSc degrees in Public Health at KU, and up to 40 trainees per site to complete online certificate programs. Workshops of special interest to research in cardiometaboic risk factors and conditions will also be offered at each site.

PI_NAMEs: FITZPATRICK, ANNETTE L. (contact);OSOTI, ALFRED ONYANGO

PROGRAM_OFFICER_NAME: LEVINTOVA, MARYA

PROJECT_TERMS: Address;Cardiometabolic Disease;cardiometabolic risk;Caring;certificate program;Collaborations;Communities;community engagement;Country;County;Development;Diet;disability;Disease;Distance Learning;Dyslipidemias;Education;Educational workshop;empowerment;Epidemic;Epidemiology;experience;Face;Faculty;Fogarty International Center;global health;Health;Hypertension;impaired glucose tolerance;implementation science;improved;innovation;Insulin Resistance;International;Investments;Kenya;Leadership;Life Style;low and middle-income countries;member;Mentorship;Metabolic dysfunction;mortality;Nepal;next generation;Obesity;Patient Care;Prevention;programs;Public Health;Research;Research Personnel;Resource-limited setting;Risk;Risk Factors;skills;Students;symposium;Training;Training Programs;Training Support;Translations;Universities;Washington

PROJECT_TITLE: Building Capacity to Address the Burden of Cardiometabolic Risk Factors and Diseases in LMICs