NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease;Obesity

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Public Health Relevance Non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) are major medical conditions in the United States that are the leading cause of liver transplantation and for which there are no therapeutic options. The EphB/EphrinB bidirectional signaling molecules are an emerging target for effective treatment of NASH fibrosis/cirrhosis and associated metabolic disorder. The work proposed will (1) develop first-in-class small molecular weight drug-like chemical antagonists that target EphB/EphrinB bidirectional signaling, and (2) test the effectiveness of such compounds in reversing established NASH fibrosis and cirrhosis in clinically relevant small animal models.

PI_NAMEs: BOUDINA, SIHEM ;MIMCHE, PATRICE  (contact)

PROJECT_TERMS: absorption;Adult;Affect;analog;angiogenesis;Animal Model;Animals;antagonist;bariatric surgery;Binding;Biochemical;Biological Assay;Biological Availability;Biological Process;Biotechnology;Cardiovascular Diseases;Cell Communication;Cells;Chemicals;Chronic;chronic liver disease;chronic liver inflammation;Cirrhosis;clinical application;clinically relevant;Collagen;combat;commercialization;comorbidity;Coupled;Data;Development;Diabetes Mellitus;Diagnosis;Diet;Disease;Disease Management;Drug Industry;Drug Kinetics;drug-like compound;effective therapy;Effectiveness;effectiveness testing;efficacy testing;efficacy validation;Embryonic Development;EphB2 Receptor;Ephrin B Receptor;Ephrin Receptor EphB1;Ephrins;epithelial to mesenchymal transition;Excretory function;Exhibits;experimental study;FDA approved;fibrogenesis;Fibrosis;Glucose;Goals;healthcare burden;Hepatic;Hepatic Stellate Cell;Hepatocyte;High Density Lipoproteins;high throughput screening;Homeostasis;Human;Hypertension;Hypertriglyceridemia;Impairment;improved;In Vitro;in vitro Assay;in vivo;Inflammation;inhibitor;Insulin;interest;Lead;Life Style;Ligands;Liver;Liver Failure;Liver Fibrosis;liver inflammation;liver transplantation;Measures;Medical;Membrane;Metabolic;Metabolic Diseases;Metabolic dysfunction;metabolic profile;Metabolic syndrome;Metabolism;migration;Modeling;Molecular Weight;mouse model;Mus;Myofibroblast;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;Obesity;Obesity Epidemic;Oral;overexpression;Pathway interactions;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Phase;phase III trial;Play;Population;pre-clinical;prevent;Primary carcinoma of the liver cells;Process;Proliferating;Property;prototype;public health relevance;receptor;Receptor Protein-Tyrosine Kinases;Research;Resolution;response;Rodent Model;Role;Sampling;scaffold;Signal Transduction;Signaling Molecule;small molecule;Structure-Activity Relationship;Testing;Therapeutic;tissue injury;Toxic effect;Transcript;transdifferentiation;translational impact;translational potential;United States;Work;wound healing

PROJECT_TITLE: Small molecule antagonists targeting EphB receptors for the treatment of nonalcoholic steatohepatitis (NASH)


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Diabetes;Kidney Disease

ORG_CITY: ATLANTA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHYSIOLOGY

ORG_FIPS: US

ORG_NAME: MOREHOUSE SCHOOL OF MEDICINE

ORG_STATE: GA

PHR: Project Narrative Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease and end-stage renal disease. Albuminuria and excess lipid accumulation are important mechanisms for DKD progression. The proposed research will enable us to establish new therapeutic strategies to halt the progression of DKD by examining the biochemical pathways that prevent kidney cells from injury in obesity and type 2 diabetes.

PI_NAMEs: ZHAO, XUEYING  (contact)

PROGRAM_OFFICER_NAME: BISSONETTE, GREG

PROJECT_TERMS: 3-Dimensional;absorption;Acute;Affect;Albumins;Albuminuria;Alloxan;Animals;Apical;Apoptosis;Apoptotic;AQP1 gene;Autophagocytosis;Binding;Biochemical Pathway;Biological Markers;C57BL/6 Mouse;Cell Culture System;Cell Culture Techniques;Cell Death;cell injury;Cells;Chronic;Chronic Kidney Failure;cytotoxicity;Data;Deposition;diabetic;Diabetic Nephropathy;Differentiation Antigens;disease model;Disease Progression;DNA Damage;druggable target;End stage renal failure;Endocytosis;endoplasmic reticulum stress;Epithelial Cells;Epithelium;Excretory function;experimental study;Fatty Acids;Fibroblasts;Fibrosis;Genetic Transcription;Geometry;Goals;High Fat Diet;Human;In Vitro;in vivo;Inflammation;Inflammatory;Injury to Kidney;interstitial;interstitial cell;Kidney;kidney cell;Kidney Diseases;Knockout Mice;LDL-Receptor Related Protein 2;Ligands;Link;Lipids;Lipoproteins;Mediating;Modeling;Molecular;monolayer;Mus;Non-Insulin-Dependent Diabetes Mellitus;Nonesterified Fatty Acids;novel;novel therapeutic intervention;Nuclear Translocation;Obesity;Onset of illness;Organoids;overexpression;Oxidative Stress;Palmitic Acids;Pathologic;Pathway interactions;Pericytes;Phagocytosis;Pilot Projects;prevent;Prevention;Primary Cell Cultures;Profibrotic signal;promoter;Proteins;Proteinuria;Proximal Kidney Tubules;rat KIM-1 protein;Regulation;Renal function;Research;response;Role;Saturated Fatty Acids;scavenger receptor;Severities;Signal Transduction;spatiotemporal;STAT3 gene;Surface;trafficking;transcriptome sequencing;Tubular formation;two-dimensional;Up-Regulation;uptake;urinary;Urine

PROJECT_TITLE: Molecular mechanisms underlying renal lipotoxicity and DKD progression


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Clinical Research;Digestive Diseases;Genetics;Human Genome;Inflammatory Bowel Disease;Pediatric;Precision Medicine

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Very early onset inflammatory bowel disease (VEO-IBD), diagnosed at <6 years of age, is a heterogeneous, severe, potentially fatal disorder of increasing incidence, where traditional IBD treatments often fail. Single gene defects are suspected to be the cause of VEO-IBD in a large number of cases, and elucidation of genetic risk factors would undoubtedly enhance our understanding of pathogenesis and suggest novel therapeutic approaches. The goal of this proposal is to widen our genetic analysis through WGS and leverage transcriptome modifications to enhance our capacity in identifying causal variants.

PI_NAMEs: KELSEN, JUDITH RACHEL (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: 6 year old;Age;Alleles;Allelic Imbalance;Alternative Splicing;Biological;Biological Assay;Biological Process;Candidate Disease Gene;candidate identification;candidate validation;causal variant;cell type;Cells;Child;Child Care;cohort;Colon;Complex;conventional therapy;Data;Data Set;Defect;Detection;Development;Diagnosis;differential expression;Disease;disease diagnosis;disease phenotype;early onset;Event;exome sequencing;Family;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Genes;Genetic;genetic analysis;genetic risk factor;Genetic Transcription;genetic variant;genome sequencing;genome wide association study;Genomics;Goals;Heterogeneity;Immune;improved;Incidence;Individual;individualized medicine;infancy;Inflammatory Bowel Diseases;innovation;insight;Knowledge;Link;Mendelian disorder;Methods;Modification;Molecular;Morbidity - disease rate;Mutation;novel;novel therapeutic intervention;Parents;Pathogenesis;Pathway interactions;Patient Recruitments;patient subsets;Patients;Peripheral Blood Mononuclear Cell;Phenotype;Recording of previous events;Refractory;Refractory Disease;risk variant;Role;single cell analysis;single-cell RNA sequencing;Single-Gene Defect;Source;Spliced Genes;targeted treatment;Testing;Tissues;Transcript;transcriptome;transcriptome sequencing;transcriptomics;Translating;Variant;whole genome

PROJECT_TITLE: Integration of genomics and transcriptomics to investigate biological pathways in very early onset IBD

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Drug Abuse (NIDA only);HIV/AIDS;Infectious Diseases;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Prevention;Substance Misuse

ORG_CITY: BALTIMORE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE  The MACS-WIHS Data Analysis and Coordination Center (DACC) brings together two datacenters that have served successfully as the scientific partner and operations center for the MACS and WIHS cohort studies, respectively. The merged datacenter will utilize best practices from both groups to advance knowledge of the basic science, clinical science, and epidemiology of HIV infection in the US, with a focus on HIV-related comorbidities. We will provide epidemiological and statistical expertise to scientific initiatives, as well as continue our quality assurance program in partnership with the clinical research sites that integrates expertise in data management, study coordination, statistical methodology, and scientific disciplines.

PI_NAMEs: D'SOUZA, GYPSYAMBER ;GANGE, STEPHEN J (contact);GOLUB, ELIZABETH T

PROGRAM_OFFICER_NAME: PATHAK, ELIZABETH BARNETT

PROJECT_TERMS: Adherence;adjudication;Adult;American;Archives;Basic Science;Biological;Biostatistics Core;Child;Child Health;Chronic Disease;Clinical;clinical research site;Clinical Sciences;cohort;Cohort Studies;Collaborations;Communication;comorbidity;Data;Data Analyses;data centers;Data Collection;data integration;data management;Data Management Resources;Data Set;data standards;Databases;design;Discipline;Epidemiology;Event;experience;Faculty;Funding;HIV;HIV Infections;HIV/AIDS;integration site;Joints;Kidney Diseases;Knowledge;Lung;Lung Diseases;men;Methodology;Methods;Modeling;Monitor;National Heart, Lung, and Blood Institute;National Institute of Allergy and Infectious Disease;National Institute of Child Health and Human Development;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of Drug Abuse;National Institute of Mental Health;Online Systems;operation;Outcome;Participant;Pathogenesis;Periodicals;programs;Prospective, cohort study;Protocols documentation;Public Health Schools;Publications;quality assurance;Recording of previous events;recruit;repository;Research;Research Design;Research Personnel;Research Priority;Research Project Grants;Resources;Science;Site;Specimen;Standardization;System;The Multicenter AIDS Cohort Study;Training;United States National Institutes of Health;Visit;Woman;Women's Interagency HIV Study;working group

PROJECT_TITLE: Data Analysis and Coordination Center for the MACS-WIHS Combined Cohort Study


NIH_SPENDING_CATS: Aging;Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Neurosciences;Prevention;Substance Misuse

ORG_CITY: Chicago

ORG_NAME: HEKTOEN INSTITUTE FOR MEDICAL RESEARCH

ORG_STATE: IL

PHR: Project Narrative Despite the availability of potent antiretroviral therapy, HIV-infected men and women continue to suffer from premature morbidity and mortality, including cardiovascular and pulmonary disease, neurocognitive dysfunction and malignancies. The goal of the Chicago Cook County Clinical Research Site of the MACS/WIHS Combined Cohort Study is to investigate the mechanisms of HIV-associated co-morbidities in order to inform interventions that will ultimately improve the quality of life and prevent premature disability and death of people living with HIV.

PI_NAMEs: COHEN, MARDGE H;FRENCH, AUDREY  (contact);ROSS, RYAN DEE

PROJECT_TERMS: Address;adjudication;Advisory Committees;Advocacy;Affect;Age;Aging;antiretroviral therapy;Applications Grants;Area;Award;behavioral health;Behavioral Sciences;Biological Testing;Cardiovascular Diseases;Cardiovascular system;career;Cessation of life;Chicago;Chronic Disease;Cities;Clinical;Clinical Data;clinical research site;cohort;Cohort Studies;Collaborations;collaborative approach;Collection;Communities;community engagement;Community Health;community partners;comorbidity;Complex;Consent;Consequences of HIV;cooking;Cost efficiency;County;Data;Data Analyses;Development;disability;Disparity;Distress;Education;Educational process of instructing;Enrollment;Epidemiology;Ethics;flexibility;Fostering;Functional disorder;Funding;Future;Goals;Grant;Health;Health Sciences;HIV;HIV therapy;HIV/AIDS;improved;innovation;insight;Intervention;Language;Lead;Leadership;Learning;Life;Liver diseases;Lung;Lung Diseases;Malignant Neoplasms;Medical;men;Mental disorders;Mentorship;Metabolic;microbiome;microbiome research;Morbidity - disease rate;mortality;multidisciplinary;National Institute on Minority Health and Health Disparities;Neurocognition;Neurocognitive;opportunistic pathogen;Oral health;Outcome;Participant;participant retention;Pathogenesis;Persons;Positioning Attribute;premature;prevent;Protocols documentation;Publications;Qualifying;Quality of life;Race;Recording of previous events;recruit;Research;Research Personnel;Resources;Risk;Sampling;Science;Scientist;Site;Sleep;social media;social stigma;socioeconomics;Specimen;stressor;Structure;Substance abuse problem;success;Surveys;Time;translational approach;urban poverty;Woman;Women's Interagency HIV Study;Women's study

PROJECT_TITLE: MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS)


NIH_SPENDING_CATS: Aging;Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Drug Abuse (NIDA only);HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurosciences;Prevention;Substance Misuse

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: EMORY UNIVERSITY

PHR: Project Narrative The overarching goal of the Atlanta Clinical Research Site (CRS) is to advance the unified scientific agenda of the MACS/WIHS CCS by: a) providing leadership in the development of the unified science protocols; b) serving as a local reading center and support laboratory for studies; and c) leveraging our research infrastructure to implement the CCS protocols by retaining current participants, recruiting new participants from under-represented minority groups, and engaging Emory scientists and the local community in CCS science and activities.

PI_NAMEs: OFOTOKUN, IGHOVWERHA  (contact);SHETH, ANANDI NAYAN;WINGOOD, GINA MARIA

PROJECT_TERMS: adjudication;Advisory Committees;Affect;Age related comorbidities;Ancillary Study;Award;base;Biological;career development;Career Mobility;Caring;Clinic;Clinical;Clinical Research;clinical research site;cohort;Cohort Studies;Communities;community advisory board;community engagement;Community Outreach;Consent;Data;data quality;Databases;Dedications;Development;disease registry;Enrollment;Environment;Epidemic;Event;Faculty;Fostering;Foundations;Funding;Funding Agency;Goals;good laboratory practice;Growth;Health;health disparity;HIV;HIV diagnosis;HIV Seropositivity;Home;Individual;innovative technologies;Institution;K-Series Research Career Programs;Laboratory Study;Lead;Leadership;Link;Location;Mediation;men;men who have sex with men;Mentored Clinical Scientist Development Program;Mentorship;Minority Groups;multidisciplinary;next generation;operation;Participant;Pathogenesis;Patients;Persons;Pharmacologic Substance;Population Heterogeneity;Principal Investigator;Procedures;Productivity;programs;Protocols documentation;Publications;Quality Control;Reading;recruit;Research;Research Activity;Research Infrastructure;Research Personnel;Resources;Risk;Role;Rural;Science;Scientist;Site;Specimen;Structure;Training;Underrepresented Minority;United States National Institutes of Health;Visit;volunteer;Woman;Women's cohort

PROJECT_TITLE: Atlanta MACS/WIHS Combined Cohort Study Clinical Research Site


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Precision Medicine;Psychosis;Schizophrenia;Serious Mental Illness

ORG_CITY: DALLAS

ORG_DEPT: PSYCHIATRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Treatment advances in psychosis may be limited by the use of phenomenology-defined diagnoses based on symptomatic outcomes, rather than by neurobiological constructs monitored by quantitative characteristics. The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) uses biomarkers to define psychosis subgroups with the goal of testing the advantages of B-SNIP biomarkers for diagnostic and therapeutic decisions, consistent with principles in the NIMH Strategic Plan. We propose to test Biotype1 psychosis subgroup with clozapine, and predict a differential clinical response to clozapine compared with Biotype2, marked by normalization of IEA, cortical attractor network activity and an advantage over usual antipsychotic drugs, establishing low IEA in Biotype1 as a predictive biomarker for clozapine efficacy.

PI_NAMEs: TAMMINGA, CAROL A (contact)

PROGRAM_OFFICER_NAME: RUDORFER, MATTHEW V

PROJECT_TERMS: anti-depressive agents;Antipsychotic Agents;Bacterial Artificial Chromosomes;Biological Markers;biotypes;blind;Blinded;Blood;Characteristics;Chemistry;Clinical;Clinical assessments;clinical efficacy;Clinical Trials;Clinical Trials Cooperative Group;Clinical Trials Design;Clozapine;Cognition;Communities;Complex;Consent;deviant;Diagnosis;Diagnostic;Dose;Double-Blind Method;Dropout;Drug Monitoring;Electrocardiogram;Electroencephalography;forging;Future;Goals;Grant;improved;Individual;Libraries;Measures;Monitor;Myocarditis;National Institute of Mental Health;neural;Neurobiology;Neutropenia;Outcome;Participant;Patients;Pharmaceutical Preparations;Pharmacotherapy;phenomenological models;Phenotype;phenotypic biomarker;Physicians;Physiological;Plasma;predictive marker;Preparation;proband;Prognosis;Psychoses;Randomized;recruit;Regimen;research clinical testing;Resistance;response;Risperidone;Saccades;Safety;Sampling;Schedule;Schizophrenia;Seizures;side effect;Site;Specific qualifier value;stimulus processing;Strategic Planning;Subgroup;symptomatic improvement;Symptoms;Testing;Therapeutic;Time;Titrations;treatment duration;volunteer;Work

PROJECT_TITLE: 1/5 - Selective Antipsychotic Response to Clozapine in B-SNIP Biotype-1 (Clozapine)


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: LOS ANGELES

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: PROJECT NARRATIVE This Program Project Grant is designed to investigate the effects of obesity on pancreatic cancer development and to evaluate potentially preventive/interceptive strategies. The Program consists of three highly synergistic and integrative Projects, which are led by experienced pancreatic cancer researchers with proven track record of successful collaboration for more than 12 years. The Projects are supported by an Administrative Core and one Shared Resource Core (Animal and Cell Model Core).

PI_NAMEs: EIBL, GUIDO ERWIN MICHAEL (contact)

PROGRAM_OFFICER_NAME: KUMAR, AMIT

PROJECT_TERMS: Adipose tissue;Advocate;Animal Model;Animals;Anti-diabetic Drugs;Anti-Inflammatory Agents;Biological;Biometry;cancer prevention;Cell Culture Techniques;Cell model;Chemoprevention;chronic pancreatitis;Clinical;clinical practice;Collaborations;Complex;Data;design;Development;Diabetes Mellitus;diet-induced obesity;Dietary Component;Disease;disorder prevention;Event;Excision;experience;Genetic;Genetic Engineering;Goals;Growth;Health Promotion;high risk;Inflammation;innovation;insight;Intercept;Interdisciplinary Study;International;Intervention;Intervention Studies;Investigation;Lipids;Malignant neoplasm of pancreas;Malignant Neoplasms;Medical center;Metformin;Modeling;Mutate;novel;obese patients;Obesity;Pancreas;pancreas development;Pancreatic Adenocarcinoma;pancreatic stellate cell;Pathology;Patient Care;Patients;prevent;Prevention strategy;Preventive;Primary Prevention;Program Research Project Grants;programs;Recommendation;Research;Research Personnel;Resource Sharing;Risk;Role;Secondary Prevention;Signal Transduction;synergism;translational impact;translational potential;tumor;Tumor Promotion;Tumor-associated macrophages

PROJECT_TITLE: Chemoprevention and mechanisms of obesity-promoted pancreatic adenocarcinoma


NIH_SPENDING_CATS: Infectious Diseases;Lung;Rare Diseases

ORG_CITY: DENVER

ORG_NAME: NATIONAL JEWISH HEALTH

ORG_STATE: CO

PHR: PROJECT NARRATIVE This proposal aims to understand why nontuberculous mycobacteria (NTM) act as opportunistic pathogens that are readily cleared by healthy lungs but can cause pulmonary infections in individuals with chronic airway diseases. Using animal models and human cells, we will characterize initial events that occur when NTM interact with specific immune cells (macrophages), and demonstrate how local environments within different parts of the lung determine whether or not macrophages can kill inhaled NTM. Results from the proposed research will aid development of novel therapies to treat non-resolving NTM infections in people with chronic airway diseases.

PI_NAMEs: HISERT, KATHERINE B (contact)

PROGRAM_OFFICER_NAME: MONGODIN, EMMANUEL FRANCK

PROJECT_TERMS: Acceleration;Address;Agar;Airway Disease;airway obstruction;alveolar epithelium;Alveolar Macrophages;Alveolus;Animal Model;antimicrobial;Bathing;Blood;Blood Circulation;Bronchiectasis;Case Study;Categories;Cells;Chronic lung disease;chronic respiratory disease;Clinical;Colony Stimulating Factor Activation;conditional knockout;cytokine;Data;Development;Disease;Disease susceptibility;Distal;enhancing factor;Environment;Epithelial Cells;Event;Exposure to;Goals;Grant;Granulocyte-Macrophage Colony-Stimulating Factor;Granulocyte-Macrophage Colony-Stimulating Factor Receptors;Growth;Heterogeneity;high risk;Human;human data;Immune;Immunologics;Immunotherapy;improved;In Vitro;Individual;Infection;Inhalation;innovation;Knockout Mice;Knowledge;Legal patent;Location;Lung;Lung infections;Macrophage;Macrophage Colony-Stimulating Factor;Macrophage-Activating Factors;Measures;Mediating;Methods;Modeling;Molecular;monocyte;mouse model;Mucociliary Clearance;Mus;mycobacterial;Mycobacterium abscessus;Mycobacterium avium;Mycobacterium Infections;non-tuberculosis mycobacteria;novel;novel therapeutics;opportunistic pathogen;pathogen;Patients;Persons;Phagolysosome;Phagosomes;Phenotype;Predisposition;Prevalence;Production;pulmonary function decline;recruit;Reporter;Research;Respiratory System;Respiratory Tract Infections;Risk;Role;Stains;Symptom Burden;Symptoms;Testing

PROJECT_TITLE: GM-CSF, macrophages, and susceptibility to Mycobacterium abscessus pulmonary infection

STUDY_SECTION: LCMI

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


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

PHR: PROJECT NARRATIVE This project is part of a Program Project designed to determine the effects of obesity on tumor promotion in an animal model of pancreatic cancer. We will test the hypothesis that obesity leads to visceral adipose tissue inflammation, which promotes pancreatic cancer development, and investigate the effects of the lipid-lowering drugs, statins, on adipose tissue inflammation and pancreatic cancer development. Our studies will provide the scientific rationale for the use of statins in chemoprevention of pancreatic cancer.

PROJECT_TERMS: Acceleration;Adipocytes;Adipose tissue;Animal Model;Anti-Inflammatory Agents;Attenuated;cancer prevention;CCL2 gene;Cells;Chemoprevention;Chronic Disease;Complex;cytokine;design;Development;Diabetes Mellitus;Diet;diet-induced obesity;Dietary Component;Disease;Dose;drug repurposing;Economics;efficacious intervention;Excision;FDA approved;gastrointestinal;Genetic;Growth;Growth and Development function;high risk;Incidence;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Infiltrate;Intervention;Kinetics;KRAS oncogenesis;KRASG12D;Lesion;Life;Link;Lipids;lipophilicity;Macrophage;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Metabolic Diseases;Molecular;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;Non-Malignant;novel;novel strategies;obese patients;Obesity;Obesity associated cancer;obesity genetics;obesogenic;Organoids;Outcome;Pancreas;pancreas development;Pancreatic Adenocarcinoma;pancreatic cancer model;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;Pancreatic Intraepithelial Neoplasia;Pathway interactions;Patients;Pharmaceutical Preparations;Play;Positive Reinforcements;prevent;Primary Prevention;Production;programs;Proliferating;rho;Risk Factors;Role;Secondary Prevention;Signal Transduction;Societies;Sociology;Testing;Time;Tissues;TLR4 gene;Transcription Coactivator;translational approach;translational impact;tumor;Tumor Promotion;Visceral

PROJECT_TITLE: Project 1: Adipose tissue inflammation in obesity-promoted pancreatic cancer


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

PHR: Project Narrative (Public Health Relevance Statement) Bromodomain-containing protein 4 (BRD4) is an emerging cancer therapeutic target whose functional inhibition by two widely used small compounds (JQ1 and I-BET) often leads to suppression of cancer-associated phenotypes; nevertheless, insensitivity to drug treatment and development of drug resistance upon prolonged treatment remain serious concerns in cancer therapy. In our preliminary studies, we found that BRD4 has two predominant protein isoforms with the long (L) form likely being tumor-suppressive and the short (S) form potentially being oncogenic. In this proposal, we will investigate the functional role of BRD4-L and BRD4-S in regulating breast cancer cell growth and tumor progression and in gene programming using biochemical and molecular biological approaches, synthetic chemistry, genomics, proteomics, and mouse breast cancer tumor models with concurrent analysis of human breast cancer specimens, which collectively will unravel the mechanisms by which BRD4 regulates normal and cancer cell growth and tumor progression as well as provide a rationale for BRD4-targeted cancer therapy.

PI_NAMEs: CHIANG, CHENG-MING  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Acute Myelocytic Leukemia;Address;Animal Model;Antibodies;Binding;Biochemical;Biological;Biological Assay;BRD2 gene;Breast Cancer Cell;Breast Cancer Treatment;Bromodomain;Bromodomains and extra-terminal domain inhibitor;Burkitt Lymphoma;c-myc Genes;cancer cell;Cancer Cell Growth;cancer gene expression;cancer heterogeneity;cancer initiation;Cancer Patient;cancer subtypes;cancer therapy;cancer type;Cathepsins;Cell model;cell motility;Cell Proliferation;Cells;Chemicals;Cholesterol;Chromatin;Classification;Clinical;Clinical Trials;Cultured Cells;Cystatins;Detection;Development;Disease;DNA;DNA Sequence Alteration;drug development;drug resistance development;Enhancers;Epidermal Growth Factor Receptor;Epigenetic Process;ERBB2 gene;ESR1 gene;Estrogen receptor positive;Extracellular Matrix;Family member;Fos-Related Antigens;Future;gain of function;Gene Cluster;Gene Expression;Gene Targeting;Genes;Genetic;Genetic Heterogeneity;genetic signature;Genetic Transcription;genome wide association study;genome-wide;Genomics;Goals;Hematologic Neoplasms;Hematopoietic Neoplasms;Histologic;Homeobox;Human;In Vitro;in vivo;Individual;Inflammatory;inhibitor;knock-down;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Mammary Neoplasms;medical attention;Metastatic breast cancer;mevalonate;Modeling;Molecular;molecular marker;mouse model;Mucins;Multiple Myeloma;Mus;mutant;Neoplasm Metastasis;NF-kappa B;Nonmetastatic;Normal Cell;Oncogenes;Oncogenic;Outcome;Pathologic;Pathway interactions;Patients;personalized medicine;pharmacologic;Pharmacotherapy;Phenotype;Positioning Attribute;posttranscriptional;pre-clinical;progesterone receptor positive;programs;Property;Protein Family;Protein Isoforms;protein protein interaction;Proteins;Proteomics;public health relevance;Regimen;Regulation;Role;Solid Neoplasm;Specimen;Stress;Surveys;Synthesis Chemistry;targeted cancer therapy;targeted treatment;Testing;therapeutic target;tool;TP53 gene;trait;transcription factor;transcriptome;transcriptomics;transgene expression;treatment planning;triple-negative invasive breast carcinoma;tumor;tumor microenvironment;tumor progression;tumorigenesis;Variant;whole genome;Work

PROJECT_TITLE: Opposing Functions of BRD4 Isoforms in Breast Cancer

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Cancer;Clinical Research;Diabetes;Digestive Diseases;Genetics;Nutrition;Obesity;Pancreatic Cancer;Prevention;Rare Diseases

PHR: PROJECT NARRATIVE The central hypothesis to be tested in this Project is that statins significantly delay or prevent the tumor-promoting effects of the high fat, high calorie diet (HFCD) either singly or acting synergistically with metformin. Since statins, including simvastatin, are FDA-approved drugs widely used in the prevention and treatment of cardiovascular diseases, the outcome of the studies will provide the scientific rationale for its use in chemoprevention of pancreatic cancer and elucidate its mechanism. Our results may also be transferable to other obesity-related cancer and even non-malignant chronic diseases.

PI_NAMEs: ROZENGURT, JUAN ENRIQUE (contact)

PROJECT_TERMS: Acinus organ component;Adipose tissue;Anchorage-Independent Growth;Anti-diabetic Drugs;atorvastatin;Attenuated;Biological Availability;Calories;Cancer Etiology;Cardiovascular Diseases;Cell Proliferation;Cells;cerivastatin;Cessation of life;Chemoprevention;Chemopreventive Agent;Cholesterol;Chronic;Chronic Disease;Clinical;clinically significant;combinatorial;connective tissue growth factor;CXCL5 gene;design;Development;Diet;diet-induced obesity;dietary control;DNA biosynthesis;Dose;Duct (organ) structure;epidemiology study;Epidermal Growth Factor Receptor;Family;Fatty acid glycerol esters;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Gene Modified;Genes;Genetic Transcription;Growth;Growth Factor;Human;human disease;Hyperinsulinism;in vivo;Inflammation;Insulin;Insulin Resistance;insulin signaling;Insulin Signaling Pathway;Insulin-Like Growth Factor I;Insulin-Like-Growth Factor I Receptor;interest;Knowledge;KRAS2 gene;KRASG12D;Lesion;Link;Lipids;lipophilicity;Malignant neoplasm of pancreas;Malignant Neoplasms;Metabolic Diseases;Metaplasia;Metformin;Modeling;Molecular;mouse model;Mus;Mutation;neoplastic;Non-Insulin-Dependent Diabetes Mellitus;Non-Malignant;novel;Nutrient;Obesity;Obesity associated cancer;obesity genetics;obesogenic;Oral Administration;Organoids;Outcome;Outcome Study;Pancreas;pancreas development;Pancreatic Adenocarcinoma;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;Peripheral;Pharmaceutical Preparations;pre-clinical;preclinical study;prevent;Prevention;Prevention strategy;programs;Proliferating;protein expression;receptor;Receptor Signaling;Research;restraint;rho;Risk;sensor;Signal Pathway;Signal Transduction;Simvastatin;Site;Survival Rate;System;Testing;therapeutic development;Transcription Coactivator;Translations;Tumor Promotion;United States Food and Drug Administration

PROJECT_TITLE: Project 2: Chemoprevention of pancreatic cancer with lipid-lowering and antidiabetic agents


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Neurosciences

ORG_CITY: LEUVEN

ORG_COUNTRY: BELGIUM

ORG_FIPS: BE

ORG_NAME: KATHOLIEKE UNIVERSITEIT LEUVEN

PHR: PROJECT NARRATIVE Noninvasive neuromodulation methods hold great promise for treating a wide range of neurological and psychiatric disorders. However, reported effects are often small, difficult to reproduce and the basic mechanisms underpinning them are not clear. Understand the basic tDCS mechanism is the first step towards improving noninvasive neuromodulation methods, leading to improved therapies for neurological and psychiatric disorders.

PI_NAMEs: MC LAUGHLIN, MYLES  (contact)

PROGRAM_OFFICER_NAME: TILGHMAN, JESSICA IRENE

PROJECT_TERMS: addiction;Affect;Anesthetics;Animal Experiments;Animals;Automobile Driving;Behavioral;Brain;Cell Nucleus;Cephalic;Cervical nerves;Clinical Trials;Cognitive;Communication;compare effectiveness;Cranial Nerves;cranium;Cream;Development;Devices;Effectiveness;effectiveness evaluation;electric field;Electrodes;Electrophysiology (science);empowerment;experience;experimental study;Funding;healthy volunteer;Human;Human Resources;Impaired cognition;improved;insight;Investigation;Knowledge;Learning;locus ceruleus structure;Marketing;Medical;Membrane;Memory;Mental Depression;Mental disorders;Methods;mild cognitive impairment;Monitor;Motor;Motor Cortex;Motor Evoked Potentials;motor learning;Nature;Nervous System Disorder;neural;neuromechanism;Neurons;neurophysiology;neuroregulation;Norepinephrine;novel;Peripheral Nerve Stimulation;Peripheral Nerves;pharmacologic;Positioning Attribute;Publications;Rattus;Reporting;Reproducibility;Resources;Role;Route;Sales;Scalp structure;Schizophrenia;Series;skills;Sympathetic Nervous System;Synaptic plasticity;Testing;Time;transcranial direct current stimulation;transcutaneous stimulation;Trigeminal nerve structure;Work

PROJECT_TITLE: Elucidating the neural mechanisms behind transcranial direct current stimulation

STUDY_SECTION: EITN

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


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: BLACKSBURG

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

ORG_STATE: VA

PHR: PROJECT NARRATIVE: Despite significant progress in the fight against pancreatic cancer, survival rates are dismal and the prognosis remains bleak, with less than 7% of patients living longer than 5 years following diagnosis. There is a dire need for new treatment strategies and pre-clinical models to evaluate emerging therapeutic approaches. This interdisciplinary proposal will deploy histotripsy, which is the first non-invasive, non-ionizing, non-thermal, image-guided tumor ablation modality that destroys tumors through the precise control of acoustic cavitation, targeting pancreatic cancer in pre-clinical mouse and novel orthotopic pig models.

PI_NAMEs: ALLEN, IRVING C (contact)

PROGRAM_OFFICER_NAME: BUCHSBAUM, JEFFREY

PROJECT_TERMS: Ablation;Acoustics;Aftercare;Anatomy;Animal Model;anti-tumor immune response;Antitumor Response;bile duct;Blood Vessels;Cancer cell line;Cessation of life;Chemotherapy and/or radiation;Clinical;clinical translation;Clinical Trials;clinically relevant;Complication;Data;Development;Diagnosis;Diameter;Disease;Dose;Duct (organ) structure;effective therapy;Electroporation;Family suidae;Feedback;fighting;Focused Ultrasound Therapy;Future;Human;image guided;Immune response;Immunocompetent;Immunocompromised Host;improved;In Situ;in vivo;Injury;instrument;Intestines;ionization;Location;Malignant neoplasm of pancreas;Malignant Neoplasms;Mechanics;Methods;millimeter;Modality;Modeling;mouse model;Mus;Nodule;novel;novel therapeutic intervention;Pancreas;pancreatic cancer cells;pancreatic cancer model;pancreatic cancer patients;Pancreatic duct;pancreatic neoplasm;Pancreatitis;patient derived xenograft model;Patients;physical property;Physiological;porcine model;pre-clinical;Pre-Clinical Model;preservation;prevent;Prognosis;Pulse Pressure;real-time images;Recurrence;Research;response;Risk;Rupture;Safety;Shapes;Site;Stenosis;Structure;Survival Rate;Techniques;Testing;Therapeutic;Time;Tissues;Transducers;translation to humans;Treatment Protocols;treatment strategy;tumor;tumor ablation;tumor progression;tumor xenograft;United States;Unresectable;Work

PROJECT_TITLE: Deploying Histotripsy Based Tumor Ablation Strategies to Treat Pancreatic Cancer

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


PHR: PROJECT NARRATIVE This project is designed to determine the effects of obesity on tumor promotion in experimental models of pancreatic cancer. We will test the hypothesis that obesity produces unique signals in the microenvironment of developing pancreatic cancer that are responsible for alterations in tumor fibroblastic cells called pancreatic stellate cells (PaSC) so that they produce signals that promote proliferation and apoptosis resistance in the cancer cells as well as shift the immune response in the tumor making it resistant to immune defenses. We will also test if the cholesterol lowering drug simvastatin and the anti-diabetes drug metformin prevent these PaSC promoting effects on the developing tumor.

PI_NAMEs: PANDOL, STEPHEN J. (contact)

PROJECT_TERMS: Acceleration;Animals;Apoptosis;Attenuated;Autophagocytosis;Calories;cancer cell;Cancer Cell Growth;Cancer Death Rates;Cancer Etiology;cancer risk;Cell Count;cell growth;Cell Physiology;cell type;Cells;Characteristics;chemokine;Chemoprevention;Chemopreventive Agent;Cholesterol;Chronic;Coculture Techniques;Collaborations;Complex;Cues;cytokine;Data;Databases;Death Rate;Deposition;design;Development;Diabetes Mellitus;Diagnosis;Diet;diet-induced obesity;Disease;Disease-Free Survival;Early Diagnosis;Environment;Excision;Experimental Models;extracellular;Extracellular Matrix Proteins;Fatty acid glycerol esters;fighting;FRAP1 gene;Genetic;Growth Factor;high risk population;Immune;Immune response;Immune system;immunoregulation;improved;improved outcome;in vitro Model;in vivo;Incidence;Induction of Apoptosis;Inflammatory;insight;Insulin;Insulin Resistance;insulin signaling;Insulin-Like Growth Factor I;interest;Interleukin-13;Interleukin-4;Interleukins;KRAS oncogenesis;KRASG12D;Leptin;Macrophage;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;Metabolism;Metformin;Mind;Mitochondria;Monitor;mortality;mouse model;Mus;mutant;Mutation;Myofibroblast;neoplastic cell;novel;Obese Mice;Obesity;obesity prevention;obesogenic;Oncogenic;Operative Surgical Procedures;Organoids;Outcome;Pancreas;Pancreatic Adenocarcinoma;pancreatic cancer model;Pancreatic Intraepithelial Neoplasia;pancreatic stellate cell;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Pilot Projects;Play;pre-clinical;prevent;prevention clinical trial;Prevention strategy;Process;programs;Proliferating;Proteins;Regimen;Relapse;Research Personnel;Resectable;Resistance;response;Risk;Role;Signal Transduction;Simvastatin;ST13 gene;STAT3 gene;success;Survival Rate;System;Testing;Time;Tissues;Transforming Growth Factor beta;tumor;tumor microenvironment;tumor progression;Tumor Promotion;tumorigenesis;tumorigenic;Weight Gain;Wild Type Mouse

PROJECT_TITLE: Project 3: Role of the pancreatic fibroinflammatory microenvironment in obesity-promoted pancreatic cancer


ADMINISTERING_IC: HD

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

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

NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: DURHAM

ORG_DEPT: GENETICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative The Developmental & Stem Cell Biology (DSCB) Program provides innovative training for the next generation of scientists and fosters discoveries that improve an understanding of developmental diseases. This research may translate to treatments that improve human health, reduce illness, repair tissue damage and lengthen life.

PI_NAMEs: SILVER, DEBRA  (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Development;stem cell biology;Training Programs

PROJECT_TITLE: Training Program in Developmental and Stem Cell Biology


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Congenital Structural Anomalies;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Various types of extracellular matrix (ECM) play important roles in shape and pattern formation during cardiac development through dynamic interactions with cells. Our research team will create three-dimensional human embryonic heart models that mimic chamber formation, and utilize artificial intelligence (AI) and ECM microarrays to identify the ECM that most effectively induces chamber-shape formation. Then, we will analyze the biological and physical effects of the optimized ECM at single-cell resolution to elucidate the mechanisms of ECM-cell interactions for cardiac development.

PI_NAMEs: RAJADAS, JAYAKUMAR ;WONG, WING H.;WU, JOSEPH C. (contact)

PROGRAM_OFFICER_NAME: THAKAR, RAHUL GAUTAM

PROJECT_TERMS: 3-Dimensional;African American population;Artificial Intelligence;Asian population;Biochemical;Biocompatible Materials;Bioinformatics;Biological;Candidate Disease Gene;Cardiac;Cardiac Myocytes;cardiogenesis;Caucasians;cell behavior;Cell Communication;Cell Differentiation process;Cell Separation;Cells;Clover;congenital heart abnormality;Data Set;deep neural network;Development;Developmental Process;differentiation protocol;Elasticity;Embryonic Heart;Extracellular Matrix;Genomics;Heart;Heart Diseases;Hispanic Populations;Human;human induced pluripotent stem cells;Image;improved;induced pluripotent stem cell;Life;Machine Learning;machine learning prediction;malformation;Measurement;Measures;mechanical signal;Mechanics;mechanotransduction;Modality;Modeling;Modulus;Morphogenesis;Morphology;multiple omics;novel;Organoids;Pattern;Pattern Formation;Play;prevent;Property;Reporter;Reproducibility;Research;Resolution;Role;screening;Shapes;Signal Pathway;Signal Transduction;Standardization;System;Therapeutic;Training;training data;Validation;Variant;Wing

PROJECT_TITLE: Elucidating ECM Signaling in Cardiac Organoids with Machine Learning and Single-cell Multiomics

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Obesity;Pancreatic Cancer;Prevention;Rare Diseases

PI_NAMEs: GO, VAY LIANG W (contact)

PROJECT_TERMS: Adipose tissue;Advisory Committees;Alcohols;Animal Model;Animals;Anti-diabetic Drugs;Area;Biometry;Budgets;California;Cell model;Chemoprevention;Clinical Sciences;Collaborations;Communication;Computer software;Consultations;Core Facility;daily functioning;Data;Data Analyses;data management;data sharing;design;Digestive System Disorders;Ensure;Funding;gang;Goals;Grant;Healthcare Systems;Inflammation;Information Dissemination;Institution;Laboratories;Lipids;Liver diseases;Los Angeles;Malignant neoplasm of pancreas;Manuscripts;Medical center;meetings;member;Methodology;Minority;Monitor;National Cancer Institute;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute on Alcohol Abuse and Alcoholism;Obesity;Occupational activity of managing finances;Pancreas;Pancreatic Adenocarcinoma;Pancreatic Diseases;Policies;Preparation;Principal Investigator;professor;Program Research Project Grants;programs;Progress Reports;Protocols documentation;Recommendation;Records;recruit;Research;Research Personnel;Research Project Grants;Resource Sharing;Resources;Role;Schedule;Services;Specific qualifier value;Statistical Study;symposium;Translational Research;Woman

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Hematology;Lymphatic Research

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Sinusoidal and lymphatic vessels are lined by distinct, VEGFR3-expressing endothelial cells, but the mechanisms by which these specialized vasculatures grow remain incompletely understood. Our preliminary studies reveal a reciprocal negative regulatory loop between VEGFC-VEGFR3 signaling and CDH5 function such that gain of CDH5 function confers loss of sinusoidal or lymphatic growth like that observed with loss of VEGFC or VEGFR3, and loss of CDH5 function enables growth of sinusoidal and lymphatic vessels in the complete absence of VEGFR3. This proposal will define the molecular mechanisms of this regulatory axis, and test the ability of CDH5 manipulation to enhance sinusoidal and lymphatic growth in mature animals to improve hematopoietic and lymphatic regeneration in disease states.

PI_NAMEs: KAHN, MARK L (contact)

PROGRAM_OFFICER_NAME: CATANIA, SELEN MURATOGLU

PROJECT_TERMS: Acceleration;Anemia;Animals;Blood Vessels;bone cell;Bone Marrow;Bone Marrow Transplantation;C cadherin;cadherin 5;Cadherins;cell motility;Cell Proliferation;Cytoskeleton;Defect;Disease;Edema;Endocytosis;Endosomes;Endothelial Cells;Endothelium;Erythroid;Exhibits;fetal;Fetal Liver;gain of function;Genetic;Genetic study;Growth;Hematopoiesis;Hematopoietic;Hepatocyte;improved;In Vitro;in vivo;insight;irradiation;KDR gene;loss of function;Lymph;Lymphangiogenesis;Lymphatic;Lymphatic Capillaries;lymphatic development;Lymphatic Endothelial Cells;lymphatic vessel;Lymphedema;Marrow;mature animal;Mediating;Molecular;Mus;Natural regeneration;novel therapeutic intervention;Organ;Pathway interactions;Patients;Permeability;Phenocopy;Phenotype;Phosphorylation;Pregnancy;Recovery;Regulation;Regulatory Pathway;Role;Signal Transduction;Tail;Testing;trafficking;translational impact;Translations;Tyrosine;vascular bed;Vascular Diseases;Vascular Endothelial Growth Factor Receptor-3;Vascular Endothelial Growth Factors;VEGFA gene;VEGFC gene

PROJECT_TITLE: Reciprocal VEGFC/VEGFR3-CDH5 regulation of lymphatic and sinusoidal vascular growth

STUDY_SECTION: CDD

STUDY_SECTION_NAME: Cardiovascular Differentiation and Development Study Section[CDD]


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Digestive Diseases;Nutrition;Obesity;Pancreatic Cancer;Prevention;Rare Diseases

PHR: PROJECT NARRATIVE This Core will provide the common animal/cell culture models and animal-related services to all Projects of the Program. Several animal studies will be carried out that investigate pancreatic cancer development promoted by obesity. Biological samples from this study will be shared and collaboratively examined by all three Projects.

PROJECT_TERMS: animal care;Animal Euthanasia;animal facility;animal imaging;Animal Model;animal tissue;Animals;Area;Backcrossings;Biological;Biometry;Blood;Breeding;Calories;Cell Culture Techniques;Cell model;Chemoprevention;Collaborations;Comprehensive Cancer Center;cost;Data;Data Collection;design;Development;Diet;diet-induced obesity;Dietary Component;dietary control;Digestive System Disorders;Drug or chemical Tissue Distribution;Ensure;Environment;Evaluation;experimental group;experimental study;Fatty acid glycerol esters;Flow Cytometry;Formalin;Generations;Genetic;Genetically Engineered Mouse;Genotype;Human;Human Resources;Individual;innovation;Institution;Intervention;Intervention Studies;KRASG12D;Laboratories;Laboratory Research;Leptin deficiency;Logistics;Malignant neoplasm of pancreas;Medical center;member;Modeling;Monitor;mouse model;Mus;novel;Obesity;Organoids;Pancreas;Pancreatic Adenocarcinoma;pancreatic cancer model;Pancreatic Diseases;Pancreatic Intraepithelial Neoplasia;Paraffin;Pathology;Phase;Preparation;Primary Cell Cultures;Procedures;Process;programs;Random Allocation;Randomized;Research Personnel;Resource Sharing;Resources;Sampling;Sampling Studies;Services;square foot;Standardization;three dimensional cell culture;Tissue Banks;Tissue Harvesting;tissue processing;Tissues;training project;tumor;Tumor Promotion;Work

PROJECT_TITLE: Core 1: Animal and Cell Model Core


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Eating Disorders;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Nutrition;Obesity;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: PROVIDENCE

ORG_NAME: MIRIAM HOSPITAL

ORG_STATE: RI

PHR: Project Narrative The current project targets body image as a risk factor for poor weight loss outcomes. Using the Obesity- Related Behavioral Intervention Trials (ORBIT) model, an empirically-supported body image intervention developed for adolescent females will be refined to increase suitability, appropriateness, and enhance treatment effects for women with overweight or obesity who are attempting weight loss. Utilizing a systematic approach to addressing risk factors for poor treatment outcome is aligned with priorities for personalized obesity medicine.

PI_NAMEs: OLSON, KAYLONI L. (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: Address;Adherence;Adult women;Affect;Aftercare;Area;Athletic;Behavior;Behavior Therapy;Behavioral;Behavioral Weight Control;black women;Body Image;Body mass index;Body Weight;Body Weight decreased;Calories;Clinical;Clinical Research;clinically significant;comparison control;Cues;Data;depressive symptoms;design;Development;Diabetes Mellitus;diet and exercise;dietary;Ecological momentary assessment;Education;Elements;Ensure;Environment;Ethnic Origin;Ethnic Population;Exercise;experience;Feedback;Female Adolescents;Focus Groups;follow-up;Fostering;Future;Goals;Growth;Guidelines;Health;Health Care Costs;Hospitals;Hydrocortisone;Hyperphagia;Individual;individual variation;Inflammation;Infrastructure;innovation;Intervention;Intervention Studies;Intervention Trial;Interventional Imaging;K-Series Research Career Programs;Life;Maps;Mediating;Medicine;Mentors;Mentorship;Methodology;Methods;Modeling;Obesity;Outcome;Overweight;Participant;Pathway interactions;patient oriented;Phase;Phase Ib Trial;pilot trial;Population Control;Positioning Attribute;Prediction of Response to Therapy;programs;Protocols documentation;Public Health;Quality of life;Questionnaires;Race;racial population;Randomized;Recommendation;recruit;Reporting;Research;Research Personnel;Resources;Risk;Risk Factors;Sampling;Scientist;Shapes;skill acquisition;skills;social stigma;Stigmatization;Subgroup;success;Target Populations;Teenagers;Testing;therapy development;Thinking;Thinness;Training;Training Programs;treatment effect;Treatment outcome;United States;Weight;Weight Gain;weight loss intervention;Weight maintenance regimen;White Women;Wing;Woman;women's outcomes;Women's trial;Work

PROJECT_TITLE: Addressing Body Image in Weight Management: An Overlooked Risk Factor for Poor Treatment Outcome Among Women

STUDY_SECTION: DDK

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


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Comparative Effectiveness Research;Cost Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Maternal Health;Maternal Morbidity and Mortality;Patient Safety;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Telehealth;Women's Health Research

ORG_CITY: EAST LANSING

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: African American women are three to four times more likely to die of pregnancy related complications than non- Hispanic white women. This study will scale a community, provider, and system-level intervention to reduce African American maternal morbidity and mortality disparities and will test the intervention using data from all Medicaid insured women who deliver in Michigan from 2016-2019 and 2021–2024 (approximately 540,000 births, including 162,000 births to African American women).

PI_NAMEs: JOHNSON, JENNIFER E (contact);MEGHEA, CRISTIAN IOAN

PROGRAM_OFFICER_NAME: OLADEINDE, YEWANDE A

PROJECT_TERMS: Address;Adoption;Affect;African American;African American Women;Behavior;Birth;Birth Records;built environment;Businesses;care coordination;Caring;Child;Communities;Community Health Aides;Community Healthcare;community intervention;community organizations;cost;cost effectiveness;cost-effectiveness evaluation;Country;County;Data;Data Set;Death Rate;Death Records;design;disparities in morbidity;Disparity;effectiveness evaluation;effectiveness testing;Eligibility Determination;Emergency department visit;Enrollment;evidence base;explicit bias;Face;Family;family management;flexibility;Guidelines;health disparity;Health education;Health system;Hearing;Home visitation;Hour;implicit bias;Improve Access;improved;Income;Inequity;Infant Health;Information Systems;innovation;Intervention;intervention effect;Lead;Learning;Life;Link;Maternal Health;maternal morbidity;Maternal Mortality;maternal safety;Measures;Medicaid;meetings;Michigan;Minority Women;mortality;mortality disparity;Mothers;Not Hispanic or Latino;Occupations;Outcome;Outpatients;Participant;patient safety;Perinatal;Physicians;Policies;Population;Postnatal Care;Postpartum Period;Pregnancy;Pregnancy Complications;Prenatal care;programs;Provider;Public Health;Quality of Care;Quasi-experiment;Race;racial disparity;response;Sampling;Sampling Studies;Schedule;Science;service utilization;Services;severe maternal morbidity;social health determinants;Social support;Speed;Structure;System;telehealth;Testing;Training;Visit;White Women;Woman;Women's Health;Work

PROJECT_TITLE: Meeting women where they are: Multilevel intervention addressing racial disparities in maternal morbidity and mortality


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Clinical Research;Dementia;Health Services;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: GREENSBORO

ORG_NAME: NORTH CAROLINA AGRI & TECH ST UNIV

PHR: A Diagnostic Platform for Extracellular Vesicle-Derived Biomarkers:  Towards Early Detection of Alzheimer’s Disease IMPACT STATEMENT. This work can be expected to produce the foundations for a new assay to detect Alzheimer’s disease prior to the onset of clinical symptoms. A clinical tool to screen for Alzheimer’s disease could support early interventions to improve patient prognosis and decrease both the societal and economic costs associated with long-term care.

PI_NAMEs: DELLINGER, KRISTEN  (contact)

PROGRAM_OFFICER_NAME: PEI, WUHONG

PROJECT_TERMS: Address;Affect;Affinity;Alzheimer disease detection;Alzheimer disease screening;Alzheimer's Disease;Alzheimer's disease care;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer’s disease biomarker;Amyloid beta-42;Amyloid beta-Protein;Area;Binding;biochip;Biological;Biological Assay;Biological Markers;Biomedical Research;Biosensing Techniques;Biosensor;Blood;Blood specimen;care costs;Caring;Cerebrospinal Fluid;Characteristics;Clinical;Clinical assessments;clinical diagnostics;clinical practice;Cognitive;Cognitive Therapy;Complex;cost effective;Coupled;Dementia;design;Detection;detection limit;Development;Devices;Diagnosis;diagnostic criteria;diagnostic platform;diagnostic screening;Disease;early detection biomarkers;Early Diagnosis;Early Intervention;economic cost;effective intervention;Effectiveness of Interventions;Endowment;Engineering;Environment;Enzyme-Linked Immunosorbent Assay;Executive Dysfunction;Exhibits;Experimental Designs;extracellular vesicles;Foundations;Goals;Gold;graduate student;Human;human induced pluripotent stem cells;Impaired cognition;improved;Individual;Institutionalization;Language;Long-Term Care;Molecular;Monitor;multidisciplinary;Neurofibrillary Tangles;Neurons;North Carolina;novel;Optics;Participant;patient prognosis;Patients;Pharmacologic Substance;point of care;Positioning Attribute;pre-clinical;predictive marker;prognostic tool;Protein Isoforms;Proteins;Raman Spectrum Analysis;Rapid screening;rational design;Recording of previous events;Research;Research Support;routine practice;routine screening;Sampling;screening;Screening procedure;Senile Plaques;Sensitivity and Specificity;Serum;societal costs;Societies;Source;Specificity;Spectrum Analysis;Spinal Puncture;Surface;Symptoms;tau Proteins;tau-1;Technology;Time;tool;Treatment outcome;undergraduate student;Underrepresented Populations;United States National Institutes of Health;Universities;Update;Visuospatial;Western Blotting;Work

PROJECT_TITLE: A Diagnostic Platform for Extracellular Vesicle-Derived Biomarkers - Towards Early Detection of Alzheimer's Disease


ORG_CITY: ORLANDO

ORG_NAME: UNIVERSITY OF CENTRAL FLORIDA

ORG_STATE: FL

PHR: Project Narrative Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curative therapy for hematologic malignancy; however, chronic graft-versus host disease (cGVHD) remains a significant cause of morbidity and mortality. Steroid, the standard initial therapy of cGVHD, often is unsuccessful in preventing permanent organs damage and has been associated with toxicities. This research proposal is to understand how medium chain fatty acid (MCFA) signaling regulates cGVHD pathobiology and validate MCFA- metabolism targeting as a valid approach to treat cGVHD and steroid refractory cGVHD.

PI_NAMEs: NGUYEN, HUNG  (contact)

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Adrenal Cortex Hormones;Affect;Allogenic;antagonist;B-Cell Activation;B-Lymphocytes;Biological Assay;Biological Process;Biology;Bronchiolitis Obliterans;CD8B1 gene;Cell Physiology;Cell Survival;Cells;Cellular Metabolic Process;chronic graft versus host disease;Clinical;CRISPR/Cas technology;curative treatments;Data;Development;Diet;dietary;disease model;disorder prevention;effective therapy;efficacy testing;Epigenetic Process;experimental study;fatty acid metabolism;Fatty Acids;Fibrosis;Flow Cytometry;Functional disorder;Gene Silencing;Genetic;Glucose;glucose uptake;Glutamine;Glycolysis;Goals;GPR84 gene;graft vs leukemia effect;Graft-Versus-Tumor Induction;gut microbiome;Helper-Inducer T-Lymphocyte;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;high dimensionality;Human;Immune;improved;In Vitro;Inflammation;inhibitor;Isoantibodies;Knock-out;Knockout Mice;long chain fatty acid;Mediating;Medium chain fatty acid;Metabolic;metabolic fitness;Metabolism;metabolomics;microbiome;migration;Mitochondria;mitochondrial fitness;Morbidity - disease rate;mortality;mouse model;Mus;novel;novel therapeutics;Organ;Oxidative Phosphorylation;Pathogenicity;Pathway interactions;Patients;peripheral blood;pharmacologic;Phase;Phase II Clinical Trials;Phenotype;post-transplant;preservation;prevent;Prevention;Proliferating;receptor;Refractory;Research Proposals;research study;Resources;Role;Scleroderma;Signal Transduction;single cell ATAC-seq;stable isotope;Steroids;stool sample;Structure of germinal center of lymph node;System;T cell differentiation;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Thymus Gland;Tissues;Toxic effect;Tracer;transcriptome sequencing;Transplant Recipients;tumor;Volatile Fatty Acids

PROJECT_TITLE: Targeting medium chain fatty acid metabolism for the treatment of chronic Graft-versus-Host Disease

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative This project aims to understand how alterations in insulin peptide presentation can promote changes in T cell selection that lead to increased autoimmunity and diabetes pathogenesis. Improved knowledge of how changes in peptide epitopes affect the generation of pathogenic effector T cells versus selection of suppressive T regulatory cells will have broader application to a more mechanistic understanding of T cell selection in the thymus as well as for mechansisms of peripheral tolerance. Finally, results of our work will determine if manipulation of insulin peptide epitopes can provide a potential target for furture efforts in tolerance induction and therapeutic intervention Type 1 diabetes.

PI_NAMEs: ANDERSON, MARK S (contact)

PROGRAM_OFFICER_NAME: SPAIN, LISA M

PROJECT_TERMS: Ablation;Address;Adoptive Transfer;Affect;Affinity;Agonist;Amino Acids;anergy;Antibodies;Antigens;Autoantigens;Autoimmune Diseases;Autoimmunity;autoreactive T cell;autoreactivity;Bacterial Artificial Chromosomes;Binding;Biochemical Pathway;Blood Glucose;CD4 Positive T Lymphocytes;Cells;central tolerance;Characteristics;Clonal Deletion;Collaborations;Coupling;Data;Development;Diabetes Mellitus;diabetes pathogenesis;Diabetes prevention;Disease;Disease Outcome;effector T cell;Epitopes;experience;experimental study;Future;Generations;Genes;genetic association;genome wide association study;Histocompatibility Antigens Class II;Immune Tolerance;immunoregulation;Immunotherapy;improved;Inbred NOD Mice;insight;Insulin;Insulin-Dependent Diabetes Mellitus;insulitis;invariant chain;Knock-in;Knowledge;Laboratories;Mediating;MHC Class II Genes;Modeling;mouse model;Mus;Mutation;novel;Pathogenicity;Peptide/MHC Complex;Peptides;Peripheral;peripheral tolerance;Positioning Attribute;prevent;Prevention;promoter;Regulatory T-Lymphocyte;Role;single cell sequencing;Specificity;T-Cell Immunologic Specificity;T-cell receptor repertoire;T-Lymphocyte;Testing;Therapeutic;Therapeutic Intervention;Thymus Gland;thymus transplantation;Time;TNFSF11 gene;tool;Transgenic Mice;Transgenic Model;Transgenic Organisms;translational potential;Variant;Work

PROJECT_TITLE: Tuning peptide specifities for T cell tolerance in Type 1 diabetes

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


ORG_CITY: SAINT LOUIS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The proposed research will address the molecular mechanisms involved in the generation, storage, and conversion of energy within the cell power plant, the mitochondrion. It will also identify promising new strategies for pharmacological control of the mitochondrion to treat obesity, type II diabetes, fatty liver, and other metabolic disorders.

PI_NAMEs: KIRICHOK, YURIY  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Address;Bioenergetics;Biophysics;Cells;Chemicals;Chemosensitization;Citric Acid Cycle;Enzymes;Fatty Liver;Foundations;Generations;Inner mitochondrial membrane;Ion Transport;Measures;Mediating;Membrane Transport Proteins;Metabolic Diseases;Methods;Mitochondria;mitochondrial membrane;Molecular;Non-Insulin-Dependent Diabetes Mellitus;Nonesterified Fatty Acids;Obesity;patch clamp;Pharmaceutical Preparations;pharmacologic;Physiology;Power Plants;Proteins;Research;Structure;Therapeutic;uptake;voltage

PROJECT_TITLE: Molecular Biophysics of Mitochondrial Membranes

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


NIH_SPENDING_CATS: Cancer;Emerging Infectious Diseases;Genetics;HIV/AIDS;Hematology;Immunotherapy;Infectious Diseases;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Kaposi's sarcoma (KS) is the most common cancer in people living with AIDS, and lymphomas are the second most common. The Kaposi sarcoma herpesvirus (KSHV) also called human herpesvirus 8 (HHV-8) is the etiologic agent of KS and some lymphomas. We will develop laboratory models that resemble diseases caused by KSHV, including the immune tumor microenvironment, which will allow us to test new treatments.

PI_NAMEs: CESARMAN, ETHEL  (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: 3-Dimensional;Acquired Immunodeficiency Syndrome;Address;Affect;Africa South of the Sahara;AIDS related cancer;Animals;Antibody Therapy;Attention;B-Lymphocytes;Biopsy;Blood Vessels;candidate identification;CD4 Positive T Lymphocytes;CD8B1 gene;Cell Line;Cells;checkpoint therapy;chemotherapy;Chronic;Clinical;common treatment;Complement 3d;Cytometry;Detection;Development;Disease;Drug Targeting;Elements;Endothelial Cells;Engineering;Environment;Etiology;Evaluation;Gene Expression;Genes;Genetically Engineered Mouse;Goals;Grant;Growth;histogenesis;HIV;Human;human disease;Human Herpesvirus 8;Hydrogels;Image;Immune;immune cell infiltrate;Immunocompetent;Immunodeficient Mouse;immunoregulation;immunosuppressed;Immunotherapy;Implant;In Vitro;in vivo;in vivo Model;Individual;Infection;Inflammatory;Inflammatory Infiltrate;Kaposi Sarcoma;Laboratories;Lead;Lesion;Lymphoma;Lymphoproliferative Disorders;Lytic;Macrophage;Malignant Neoplasms;mast cell;Messenger RNA;Methods;Modeling;mouse model;Multicentric Angiofollicular Lymphoid Hyperplasia;Mus;neoplastic cell;novel;novel therapeutics;organ transplant recipient;Organoids;Pathogenesis;Pathology;Patients;Pattern;Permeability;Persons;Pharmaceutical Preparations;Phenotype;Plasma Cells;pre-clinical;primary effusion lymphoma;Process;Proteins;Research;resistance mechanism;response;Rodent;Role;Schedule;Signal Transduction;Solid;System;T-Cell Depletion;targeted treatment;Testing;Therapeutic;therapeutic evaluation;Tissues;Transcript;Translating;Translations;tumor;Tumor Biology;tumor microenvironment;tumor-immune system interactions;tumorigenesis;Viral Genes;Viral Genome;Viral Proteins;Virus;Virus Latency;Xenograft procedure

PROJECT_TITLE: (PQ 6) New Models of KSHV Oncogenesis and KS Immune Environment


NIH_SPENDING_CATS: Bioengineering;Data Science;Machine Learning and Artificial Intelligence;Nanotechnology

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Narrative  The Virtual Nanostructure Simulation (VINAS) database uses novel nanostructure annotation technique and machine learning approaches. The VINAS web portal will be the first available online data depository tool to lead the machine learning modeling of nanomaterials to guide the development of new nanomedicines.

PI_NAMEs: ZHU, HAO  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Acceleration;Address;Animal Model;Area;artificial intelligence method;Big Data;Biological Assay;Buffers;Carbon Nanotubes;Cells;chemical property;Chemical Structure;Chemistry;Communities;Complex;Computer Models;consumer product;Cyclic Peptides;cytotoxicity;Data;Data Collection;data curation;data repository;data sharing;Databases;deep learning;deep learning algorithm;deep learning model;Dendrimers;design;Development;DNA;Ensure;expectation;experimental study;explainable artificial intelligence;Fullerenes;Future;generative adversarial network;graphene;Health;Health Technology;In Vitro;in vivo;Inflammatory Response;Information Retrieval;large datasets;Lead;Ligands;Machine Learning;machine learning model;Manuals;Manuscripts;Medicine;Methods;Modeling;Modernization;Names;nano;nanoengineering;nanomaterials;nanomedicine;nanoparticle;Nanostructures;Nanotechnology;novel;Oxidative Stress Induction;Peptide Nanotubes;Physics;predictive modeling;Procedures;programs;Property;protein data bank;Proteins;Protocols documentation;PubChem;public database;Quantum Dots;Readability;Research;Resources;response;simulation;small molecule;Structure;Study models;success;Surface;Techniques;Temperature;Testing;tool;Toxic effect;uptake;user-friendly;virtual;web portal;zeta potential

PROJECT_TITLE: Virtual nanostructure simulation (VINAS) portal

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


ADMINISTERING_IC: NS

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative Expansion of a GGGGCC repeat in the C9orf72 gene is the most common known cause of two devastating neurodegenerative diseases, amyotrophic lateral sclerosis and frontotemporal dementia. This repeat generates toxic proteins in patient brains through a non-canonical form of RNA translation. My project is aimed at elucidating how this unusual form of translation works and developing tools aimed at reducing its efficiency as a path towards therapeutic development in these currently untreatable disorders.

PI_NAMEs: MILLER, SHANNON LYNNE (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Affect;Antisense Oligonucleotides;Biochemical;Biological Assay;Biological Models;Brain;C9ORF72;Cell Death Induction;Cell Nucleus;Cell Survival;Cells;Cellular Neurobiology;clinical application;Codon Nucleotides;Confocal Microscopy;Coupled;Cytoplasm;design;Dipeptides;Disease;druggable target;Enzyme-Linked Immunosorbent Assay;Enzymes;Exons;frontotemporal lobar dementia amyotrophic lateral sclerosis;Future;Generations;Genes;Genetic;Genetic Transcription;Homeostasis;immunocytochemistry;Impairment;Induced Neurons;insight;Introns;knock-down;lariat debranching enzyme;Measures;Messenger RNA;Molecular;Molecular Neurobiology;mRNA Precursor;Nature;Neurodegenerative Disorders;neuronal survival;Neurons;novel;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;patient oriented;Patients;Physiological;polysome profiling;Production;protein aggregation;protein expression;Proteins;Quantitative Reverse Transcriptase PCR;Reaction;Reading Frames;Reporter;Ribosomes;RNA;RNA Splicing;Role;Source;Techniques;Therapeutic;therapeutic development;tool;Toxic effect;Training;Transcript;Transcription Initiation;Translating;Translation Initiation;translational neuroscience;Translations;Work

PROJECT_TITLE: Determining the Mechanism of RAN Translation in C9orf72-Associated ALS/FTD

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-M(20)L]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_CITY: CAMBRIDGE

ORG_DEPT: CHEMISTRY

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: Project Narrative  Directed evolution is a valuable technique for the development and optimization of proteins with valua- ble new functions, as well as for the elucidation of fundamental biological mechanisms that impact the ability of proteins to robustly explore mutational space. A major issue that currently limits the power of these ap- proaches, however, is that current directed evolution workflows are currently performed almost exclusively in simple systems such as test tubes, yeast, or bacteria. This research will (1) build and apply next-generation, human cell-based directed evolution platforms to open new doors in research and biotechnology and (2) apply evolution strategies in human cells to illuminate how the proteostasis network impacts protein evolution, espe- cially as it relates to diseases like cancer.

PI_NAMEs: SHOULDERS, MATTHEW DONALD (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Acceleration;Address;anti-cancer research;Area;Bacteria;Biological;Biology;Biophysics;Biotechnology;Cells;Charge;chemical genetics;Chemicals;Complex;Directed Molecular Evolution;Disease;drug development;drug resistance development;Ensure;Environment;Escherichia coli;Evolution;G-Protein-Coupled Receptors;Human;inhibitor;insight;interest;Laboratories;Libraries;Lower Organism;Malignant Neoplasms;Methodology;Molecular Chaperones;mutant;Mutation;National Institute of General Medical Sciences;Neurosciences;next generation;novel;Oncogenes;Organism;Process;protein folding;Proteins;proteostasis;Research;Role;Signal Pathway;System;technique development;Testing;tool;Tube;tumorigenesis;unnatural amino acids;Variant;Yeasts

PROJECT_TITLE: Leveraging Next-Generation Directed Evolution Platforms and Chemical Control of Proteostasis to Deliver Robust Biotechnologies and Illuminate Roles of Chaperone Networks in Protein Evolution

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


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Contraception/Reproduction;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Women's Health Research

ORG_CITY: MADISON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Maternal-fetal medicine clinicians still lack the ability to understand placental health and function, critical for a successful pregnancy, in real time with non-invasive methodologies. We propose to use experimental interventions in a nonhuman primate model expected to result in inflammation, placental and decidual lesions, and disrupted intervillous blood flow to refine and optimize magnetic resonance imaging as a method for the real-time assessment of placental function. Since inflammation and disrupted blood flow are thought to be primary contributors to adverse pregnancy outcomes including fetal growth restriction, these studies will work towards the ultimate goal to be able to identify problems and “treat the placenta” to improve the health of both mothers and babies.

PI_NAMEs: SHAH, DINESH MANILAL;WIEBEN, OLIVER  (contact)

PROGRAM_OFFICER_NAME: ILEKIS, JOHN V

PROJECT_TERMS: 4D MRI;Address;adverse pregnancy outcome;Anatomy;Animals;arterial spin labeling;Biological;Biophysics;Blood flow;blood oxygen level dependent;Blood Vessels;Body Regions;Cardiovascular system;CCL2 gene;Clinic;clinical application;clinical care;contrast enhanced;Contrast Media;diagnostic accuracy;Endocrine;Experimental Animal Model;FDA approved;ferumoxytol;fetal;Fetal Development;Fetal Growth Retardation;Fetal safety;Fetus;Fibrin Tissue Adhesive;Functional disorder;Goals;Grant;Health;Hemostatic Agents;Histologic;Histopathology;Human;human subject;hypoperfusion;Hypoxemia;Hypoxia;Image;Immune response;Immunologics;immunopathology;improved;in vivo;Infiltration;Inflammation;Institutional Review Boards;Intervention;ischemic injury;Lesion;Macaca;Macaca mulatta;Macrophage;Magnetic Resonance Imaging;Maps;Maternal-Fetal Exchange;Maternal-fetal medicine;Measures;Methodology;Methods;model development;Modeling;Molecular;Mothers;Motion;nonhuman primate;novel;novel strategies;Organ;Pathologic;Pathology;Perfusion;Phagocytes;physiologic stressor;Physiological;Physiology;Placenta;Population;Positioning Attribute;predicting response;Pregnancy;pregnant;Pregnant Women;Primates;Process;prognostic value;Prospective Studies;Reproducibility;Risk;Scanning;Second Pregnancy Trimester;Spiral Artery of the Endometrium;Structure;Study Subject;Third Pregnancy Trimester;Time;tissue oxygenation;Tissues;tool;trafficking;Translating;Uterus;Validation;vascular bed;Vascular blood supply;Villous;Visualization;Work

PROJECT_TITLE: Magnetic resonance imaging of the antecedents of fetal growth restriction at the primate maternal-fetal interface


NIH_SPENDING_CATS: Bioengineering;Breast Cancer;Cancer;Immunotherapy;Nanotechnology;Women's Health Research

ORG_CITY: CLEVELAND

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE We seek to develop an immuno-stimulatory nanoparticle targeted to the perivascular regions of metastasis delivering a robust immune-potentiating stimulus. By considering the unique microenvironment of metastatic disease, the nanoparticle can produce a strong anti-tumor immune response and trigger potent activation of cytotoxic T cells that will lead to tumor rejection.

PI_NAMEs: KARATHANASIS, EFSTATHIOS  (contact);SCHIEMANN, WILLIAM

PROGRAM_OFFICER_NAME: BOURCIER, KATARZYNA

PROJECT_TERMS: Agonist;anti-cancer research;anti-tumor immune response;Antigen Targeting;Antigen-Presenting Cells;antigen-specific T cells;Area;Binding;Blood Vessels;breast cancer metastasis;Cancer Biology;cancer cell;cancer immunotherapy;CD8-Positive T-Lymphocytes;Cell Survival;Cells;Cellular Membrane;chemotherapy;Clinical;Clinics and Hospitals;Collaborations;Comprehensive Cancer Center;Cytosol;Cytotoxic agent;cytotoxic CD8 T cells;Cytotoxic T-Lymphocytes;Deposition;design;Disease;Disseminated Malignant Neoplasm;dosage;endosome membrane;Endosomes;Exhibits;Frequencies;Immune;Immune checkpoint inhibitor;Immunologic Stimulation;Immunomodulators;Immunooncology;immunoregulation;Immunosuppression;Immunotherapy;innate immune pathways;Interferon Type I;Interferon-beta;Lead;Lilium;Lipid A;Lipids;lipophilicity;Location;Malignant Neoplasms;Mediating;Mediator;Micrometastasis;mouse model;nanoparticle;nanoparticle delivery;Nanotechnology;Natural Killer Cells;neoplasm immunotherapy;Neoplasm Metastasis;neoplastic cell;Pathway interactions;Patient Care;Patients;Periodicity;Physiological;Population;Porifera;Production;programs;Protons;Publishing;recruit;Recurrence;Research Personnel;response;Route;Safety;senescence;Silicon Dioxide;Site;standard of care;Stimulator of Interferon Genes;Stimulus;Surface;synergism;Testing;TLR4 gene;Toxic effect;Treatment Efficacy;triple-negative invasive breast carcinoma;tumor;Tumor Antigens;tumor immunology;tumor microenvironment;Universities;University Hospitals;uptake

PROJECT_TITLE: Targeted immuno-nanoparticles for directing antitumor immune response against breast cancer metastasis


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Networking and Information Technology R&D (NITRD);Pediatric;Precision Medicine;Prevention;Rural Health;Social Determinants of Health;Substance Misuse;Telehealth

ORG_CITY: Springfield

ORG_NAME: OREGON RESEARCH INSTITUTE

ORG_STATE: OR

PHR: Project Narrative The vast majority of justice-involved youth struggle with multiple behavioral health problems. Substance use, disruptive behavior, depression, and trauma-related stress are among the most common co-occurring problems. A small fraction of youth receive needed treatment services as problems begin to emerge, however, due to the dearth of accessible, effective early treatment resources within the juvenile justice system. This research aims to develop and pilot test a theoretically grounded, web-based, multicomponent behavior change early intervention that features personalized, youth-centered elements to optimize efficacy, equity, usability and engagement, and that will expand access to treatment at the early-stage level for underserved adolescents.

PI_NAMEs: WALDRON, HOLLY BARRETT (contact);WINTERS, KEN C

PROGRAM_OFFICER_NAME: NICKS, SHANNON ELIZABETH

PROJECT_TERMS: Address;Adolescent;Anger;Area;Behavior;behavior change;Behavioral;behavioral health;behavioral health intervention;Caring;Cellular Phone;Characteristics;Clinical;Cognitive;comorbidity;coping;Decision Making;design;Development;digital health;Drug abuse;Early Intervention;Early treatment;eHealth;Electronics;Elements;Emotions;empowerment;Equity;ethnic minority;evidence base;Exhibits;Feedback;Feeling;Focus Groups;follow-up;Friends;Goals;handheld mobile device;Health Resources;Health Services;Health Services Accessibility;improved;Impulsive Behavior;Internet;Interpersonal Relations;Intervention;intervention cost;Justice;juvenile justice system;Link;Literature;Low income;Mental Depression;mHealth;mhealth interventions;Minority;mobile computing;Motivation;negative mood;Online Systems;Outcome;Participant;Patients;personalized approach;personalized intervention;pilot test;Population;prevent;probation;Problem behavior;programs;racial minority;Research;research and development;Resources;Risk;rural area;Rural Community;rural setting;satisfaction;screening;Screening procedure;Self Direction;Service delivery model;service intervention;Severities;skill acquisition;skills;Stress;Substance abuse problem;substance use;System;Technology;therapy development;Thinking;Training;Trauma;treatment services;Underserved Population;usability;Waiting Lists;Youth

PROJECT_TITLE: Adolescent Screening and Personalized Intervention Resource for Mild/Moderate Substance Abuse and Co-Occurring Problems

STUDY_SECTION: IPTA

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


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Eating Disorders;Mental Health;Neurosciences;Nutrition;Obesity;Pediatric;Prevention

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: NUTRITION

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: Project Narrative: Reducing excess food consumption in response to food advertising is a public health goal for preventing excess weight gain and the development of obesity in children. Food marketing is a major contributor to childhood obesity, and the proposed research will identify neurobiological and behavioral characteristics that protect some children from overeating in the presence of this cue. These findings will have direct implications for the development of more effective strategies to reduce energy intake for the prevention of obesity.

PI_NAMEs: KELLER, KATHLEEN L (contact)

PROJECT_TERMS: 8 year old;Address;Advertisements;Advertising;Affect;approach behavior;Attention;Automobile Driving;Behavioral;behavioral outcome;behavioral phenotyping;behavioral response;Brain;Brain region;Characteristics;Child;Child Development;Code;Cognitive;cognitive control;Consumption;Corpus striatum structure;critical period;Cues;Data;design;Development;Dual-Energy X-Ray Absorptiometry;Eating;Eating Behavior;eating in absence of hunger;Energy Intake;Enrollment;Environment;Etiology;Event;excessive weight gain;executive function;Exhibits;experience;Exposure to;Family;Food;food consumption;Food Energy;food marketing;Foundations;health goals;healthy weight;hedonic;high risk;Hyperphagia;Image;Individual;Individual Differences;Laboratories;Literature;Machine Learning;Measures;neural;neural circuit;neural network;Neurobiology;novel;Obesity;obesity development;obesity in children;obesity prevention;obesity risk;obesogenic;Parents;Phenotype;preadolescence;Predisposition;Prefrontal Cortex;prevent;Prevention program;prospective;Prospective Studies;Public Health;public health priorities;Research;resilience;resilience factor;Resistance;response;Rewards;Risk;Science;somatosensory;Source;Speed;Structure of postcentral gyrus;Techniques;Testing;Toy;trait;Weight;Weight Gain

PROJECT_TITLE: Characterizing resilience to food-cue induced overeating in children

STUDY_SECTION: PRDP

STUDY_SECTION_NAME: Psychosocial Risk and Disease Prevention Study Section[PRDP]


NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Sodium MRI (NaMRI) has been challenging due to inherently low signal-to-noise and resolution but holds much promise in the study of neurological diseases including Mild Traumatic Brain Injury (MTBI) where the underlying mechanisms are still unclear and effective therapies are badly needed. Here we propose innovative multinuclear imaging techniques including advances in coil design, acquisition optimization, image reconstruction as well as cutting-edge MRI microstructure modeling to optimally quantify in vivo NaMRI signal in MTBI. We will study the relationship between NaMRI, microstructural injury and clinical outcome at 3.0 Tesla, translating promising evidence from cell and animal studies to a clinical MTBI population in the search for effective noninvasive surrogate imaging markers for injury.

PI_NAMEs: LUI, YVONNE W (contact);QIAN, YONGXIAN

PROGRAM_OFFICER_NAME: UMOH, NSINI ALEASE

PROJECT_TERMS: Address;Affect;Animal Experiments;Animal Model;Animals;Axon;Biological Markers;Brain;brain tissue;Cell model;Cells;Characteristics;Clinical;clinical outcome measures;cognitive performance;Complex;Corpus Callosum;Craniocerebral Trauma;Data;Data Analyses;design;Detection;Development;Diffusion;Diffusion Magnetic Resonance Imaging;Disease;effective therapy;Evaluation;experimental study;Functional disorder;Goals;Guidelines;Homeostasis;human subject;Image;image reconstruction;imaging biomarker;Imaging Techniques;improved;In Vitro;in vivo;in vivo imaging;Incidence;Individual;individual patient;Injury;innovation;Ion Pumps;Link;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Measures;Mediating;Metabolic;Metabolic Marker;Methods;mild traumatic brain injury;Modeling;Na(+)-K(+)-Exchanging ATPase;Nervous System Disorder;Neurobehavioral Manifestations;Noise;novel;novel therapeutics;Nuclear;nuclear imaging;Outcome;outcome prediction;Pathway interactions;Patients;Physiological;Play;Population;pre-clinical;Pre-Clinical Model;Predisposition;Protons;Public Health;Recommendation;reconstruction;Recovery;Relaxation;Resolution;return to sport;Risk;risk prediction;Rodent;Role;Signal Transduction;Sodium;Sodium Channel;Structural defect;Structure;Symptom Burden;Symptoms;TBI Patients;Technology;Testing;Time;Torsion;Translating;Translations;voltage;white matter;white matter injury;Work

PROJECT_TITLE: Optimized Sodium MR Imaging at Clinical Field Strength to Study in vivo Sodium Signal in Mild Traumatic Brain Injury


NIH_SPENDING_CATS: Behavioral and Social Science;Caregiving Research;Chronic Liver Disease and Cirrhosis;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Health Services;Liver Disease;Organ Transplantation;Transplantation

ORG_CITY: PHILADELPHIA

PHR: PROJECT NARRATIVE Liver adults liver process. center among transplantation, the only lifesaving treatment for end-stage liver disease, is increasingly performed for older with multiple comorbidities. Medication adherence is key to maintaining proper function of the transplanted  and optimize overall health; however, adhering to post-transplant treatment regimens is a very complex  This clinical trial will tudy how readily available technology-enabled tools combined with transplant resources and caregiver support can optimize medication adherence, quality of life, and health outcomes new liver transplant recipients at 3 diverse centers. s

PI_NAMEs: SERPER, MARINA  (contact)

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: Address;Adherence;Adult;Affect;age group;arm;Behavior;behavioral health;behavioral study;Blood Glucose;Blood Pressure;Cardiovascular Diseases;Caregiver support;Caregivers;Caring;Chicago;Chronic Disease;Cirrhosis;Clinical;Clinical Trials;Cognitive;cohort;comorbidity;Complex;compliance behavior;cost;Cost Analysis;cost effectiveness;digital health;disorder control;dosage;Dose;Economics;effectiveness evaluation;Effectiveness of Interventions;effectiveness outcome;effectiveness testing;Electronic Health Record;Eligibility Determination;end stage liver disease;Enrollment;Ethnic Origin;Evaluation;experience;Failure;follow-up;Funding;Gender;graft function;Graft Rejection;Health;Health Care Sector;Health Promotion;Health Status;Health system;Healthcare;Hepatic Encephalopathy;Hospitalization;human old age (65+);Immunosuppression;Impaired cognition;implementation outcomes;improved;Intervention;Kidney Diseases;Kidney Transplantation;Knowledge;Language;Learning;Life;Lipids;Liver;Liver Failure;liver transplantation;Medical;medication compliance;mHealth;Monitor;mortality;Nature;novel;Nurses;older adult;Operative Surgical Procedures;Outcome;patient oriented;Patients;Pennsylvania;Pharmaceutical Preparations;Pharmacists;Phenotype;Philadelphia;post-transplant;Prevalence;Process;programs;prospective;Provider;psychologic;psychosocial;Quality of life;racial diversity;Randomized, Controlled Trials;Regimen;remote monitoring;Resources;response;side effect;social;Social Work;Spanish;Techniques;Technology;technology intervention;Testing;Time;tool;transplant centers;Transplant Recipients;Transplantation;treatment adherence;treatment as usual;treatment optimization;Treatment Protocols;United States National Institutes of Health;Universities;Waiting Lists;Work

PROJECT_TITLE: Technology Enabled Strategies to Promote Treatment Adherence in Liver Transplant: The TEST Trial

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: Project Narrative Precision medicine promises to customize medical care to the individual patient based on their genome and individual environment and behaviors. However, we lack a basic understanding of the causal connections between the genome and complex trait hierarchies, in which a suite of sub-phenotypes all contribute to produce a high-level phenotype. This research will use a model system to provide general insights into trait hierarchies, with relevance to many health-related trait hierarchies, such as coronary artery disease, exercise endurance, or metabolic syndrome.

PI_NAMEs: KING, ELIZABETH GRIEP (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Affect;Behavior;Biological Models;Caring;causal variant;Communities;Complex;Coronary Arteriosclerosis;Drosophila genus;endurance exercise;Energy Metabolism;Environment;Environmental Risk Factor;Evolution;fly;Genetic;genetic variant;Genome;Genomics;Genotype;Health;Human;Individual;individual patient;innovation;insight;Knowledge;life span;Maps;Medical;Metabolic syndrome;Phenotype;Physiology;pleiotropism;Population;precision medicine;Property;Research;trait

PROJECT_TITLE: Genome evolution across complex trait hierarchies

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Microbiome;Nutrition;Prevention

ORG_CITY: RALEIGH

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: Project Narrative The proposed research is relevant to public health because determining how C. difficile is able to benefit from the loss of colonization resistance in the gut has major implications for the development of microbiome based therapeutics for prevention and treatment of CDI and many other GI diseases. Thus, the proposed research is relevant to the part of the NIH’s mission that pertains to developing fundamental knowledge that will reduce the burdens of human illness. The research is also relevant to the part of the NIGMS’s mission that pertains to supporting basic research, which increases the understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment and prevention. The contribution of the proposed research is significant because it will define the dynamic relationship between nutrient availability and bile acid metabolism at the level of the individual microbial species in commensal Clostridia and within a microbial community. This proposal seeks to define their individual and combinatorial roles in how the gut microbiota is able to provide colonization resistance.

PI_NAMEs: THERIOT, CASEY MICHELLE (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Affect;Amino Acids;Animal Model;Antibiotics;Area;bacterial genetics;Bacterial Physiology;Basic Science;bile acid metabolism;Bile Acids;Biochemistry;Biological Process;Biomass;Clostridium difficile;colonization resistance;combinatorial;Complex;Data;design;Development;Diet;Disease;disease diagnosis;Environment;Foundations;Germ-Free;Goals;Gram-Positive Bacteria;Growth;gut microbiome;gut microbiota;Health;host-microbe interactions;Human;Immune response;improved;In Vitro;in vivo;Indigenous;Individual;Infection;Intestines;Knowledge;Laboratories;Mediating;Metabolism;metabolome;metabolomics;Methods;Microbe;microbial;microbial community;microbiome research;microbiome therapeutics;Mission;model organism;mouse model;National Institute of General Medical Sciences;novel;Nutrient;Nutrient availability;pathogen;prevent;Prevention;Production;Protein Engineering;Proteins;Proteomics;Public Health;Reproducibility;Reproduction spores;Research;Role;Shapes;Structure;Techniques;Technology;therapeutic development;Therapeutic Intervention;transcriptomics;United States National Institutes of Health

PROJECT_TITLE: The interplay between nutrient availability and secondary bile acid metabolism in commensal Clostridia mediates colonization resistance against C. difficile


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Cancer;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

ORG_STATE: CT

PHR: Public Health Relevance Statement The project is relevant to public health because it will lead to better understanding of how the immune system responds to cancer, a diverse group of diseases rooted in dysregulated cell proliferation that affect millions of Americans every year. The proposed studies would investigate the therapeutic potential of activating the immune system to fight cancer using small molecule drugs targeting BTN3A1 as well as assess potential toxicity issues that may arise.

PI_NAMEs: WIEMER, ANDREW J (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Address;Affect;Agonist;American;Animal Cancer Model;Animal Model;anti-cancer;anticancer activity;Antigens;Area;Binding;Biological;Biological Assay;butyrophilin;cancer cell;cancer immunotherapy;Cancer Model;Cancer Patient;Cell Line;Cell Membrane Permeability;Cell model;Cell Proliferation;Cells;checkpoint inhibition;chemotherapy;Clinical;Coculture Techniques;CTAG1 gene;cytokine;Cytolysis;Data;Development;Diphosphates;Disease;Dose;Drug Targeting;efficacy evaluation;Evaluation;Failure;fighting;Goals;Human;Immune;immune checkpoint;Immune checkpoint inhibitor;Immune response;Immune system;Immunologics;Immunotherapeutic agent;Immunotherapy;immunotoxicity;improved;In Vitro;in vivo;Infiltration;innovation;inorganic phosphate;Integral Membrane Protein;Kinetics;leukemia/lymphoma;Ligand Binding;Ligands;Lymphoma;Lymphoma cell;Malignant - descriptor;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Medical;Metabolism;Modeling;mouse model;Mus;neoplastic cell;Normal Cell;novel;Outcome;overexpression;Patients;Pattern;Peripheral Blood Mononuclear Cell;Permeability;Pharmaceutical Preparations;phosphonate;Phosphorus;Plasma;Population;prevent;Prodrugs;Production;programs;Property;Proteins;Public Health;public health relevance;receptor;Research;response;retention rate;Role;Safety;safety assessment;scaffold;Series;small molecule;Specificity;stability testing;T cell infiltration;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Testing;Therapeutic;Time;Toxic effect;Transplantation;tumor;Tumor Antigens;tumor growth;Tumor Immunity;tumor progression;uptake;Work;γδ T cells

PROJECT_TITLE: Synthesis and evaluation of BTN3A1 ligands for cancer immunotherapy

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


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

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE This proposed project aims to discover first-in-class small-molecule degraders of WDR5 as a novel therapeutic strategy for the treatment of MLL-rearranged leukemias. Currently, MLL-rearranged leukemia patients have a dismal prognosis and respond very poorly to standard treatments. Thus, the proposed research is directly relevant to public health.

PI_NAMEs: JIN, JIAN  (contact);WANG, G GREG

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: Acute leukemia;Acute Lymphocytic Leukemia;Acute Myelocytic Leukemia;antitumor effect;Apoptosis;Assessment tool;Binding;Biological Assay;biophysical properties;Biophysics;c-myc Genes;Cell Cycle Progression;cell killing;Cell model;Cell Proliferation;Cells;Chemicals;Childhood Leukemia;Chromatin;Clinic;Clinical Trials;Complex;design;Disease;Dose;drug candidate;Drug Kinetics;Drug Targeting;efficacy evaluation;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;Growth;histone methyltransferase;Human;improved;In Vitro;in vivo;Infant;inhibitor;innovation;knock-down;Knock-out;Lead;leukemia;Leukemic Cell;Ligands;Link;Malignant Neoplasms;Mediating;Mixed-Lineage Leukemia;MLL gene;mouse model;novel therapeutic intervention;Oncogenic;Oncoproteins;patient derived xenograft model;Patients;pharmacologic;Prognosis;programs;Proliferating;Property;Protac;protein degradation;protein protein interaction;Public Health;recruit;Reporting;Research;Resolution;response;small molecule;small molecule inhibitor;standard care;Structure;targeted treatment;Technology;Tertiary Protein Structure;Testing;Therapeutic;therapeutic target;Toxic effect;transcriptome;Translating;treatment strategy;tumor growth;tumorigenesis;ubiquitin-protein ligase;Xenograft procedure

PROJECT_TITLE: Discovery of First-in-class WDR5 PROTACs as a Novel Therapeutic Strategy for MLL-rearranged Leukemias

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]