ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Gene Therapy;Genetics;Hematology;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Stem Cell Research - Umbilical Cord Blood/ Placenta;Stem Cell Research - Umbilical Cord Blood/ Placenta - Human;Transplantation

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: The majority of patients with acute myeloid leukemia (AML) cannot be cured with currently available therapies; however, our team has demonstrated that targeting leukemia antigens using chimeric antigen receptor (CAR) T cells (i.e. 8F4-CAR-T cells) is a safe and efficacious approach to eradicate leukemic cells, including stem cells. Published clinical and preclinical data in hematologic and solid tumor malignancies show that fucosylation of T cells enhances T cell homing and cytotoxic functions. The studies proposed in this grant application will build on these data, and will allow us to obtain preclinical data to study the effects of fucosylation on CAR-T cell function, which will form the basis to develop future clinical trials evaluating adoptive T cell therapy with fucosylated CAR-T cells as a novel therapeutic strategy for patients with cancer.

PI_NAMEs: AL-ATRASH, GHEATH  (contact)

PROGRAM_OFFICER_NAME: SALOMON, RACHELLE

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adoptive Cell Transfers;Adoptive Transfer;Affinity;Allogenic;Antigen Targeting;Antigens;antitumor effect;Applications Grants;blood product;Bone Marrow;Bone neoplasms;cancer cell;cancer immunotherapy;cancer therapy;cell killing;Cell Line;Cell Physiology;Cell Therapy;Cells;Cellular immunotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;Clinical Data;clinical efficacy;clinical trial enrollment;Clinical Trials;Cord Blood stem cells;cytotoxic;Cytotoxic T-Lymphocytes;Data;Development;Disease;Dose;Effectiveness;Effector Cell;end of life care;Endothelial Cells;Engineering;Engraftment;Foundations;Fucose;Fucosyltransferase;Future;Glycoengineering;Goals;graft vs host disease;Hematologic Neoplasms;Home;Homing;Human;Immune;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;Infusion procedures;innovation;Knowledge;leukemia;Leukemic Cell;Leukocyte Elastase;Ligands;Malignant - descriptor;Malignant lymphoid neoplasm;Malignant Neoplasms;Marrow;Mediating;Membrane;Membrane Glycoproteins;Methods;mouse model;Myeloid Leukemia;neoplastic cell;Normal tissue morphology;novel;novel therapeutic intervention;Parents;participant enrollment;Patient Care;patient prognosis;Patients;Phase I Clinical Trials;pre-clinical;Predisposition;Process;Proteinase 3;Proteins;Publishing;Refractory;Regulatory T-Lymphocyte;Relapse;Research;response;Role;Safety;Selectins;Site;Solid Neoplasm;standard of care;Stem cell transplant;stem cells;success;sugar;Surface;T cell therapy;T-Cell Homing Receptors;T-Lymphocyte;Testing;Therapeutic;Tissues;Toxic effect;treatment strategy;tumor;Tumor Antigens;Tumor Tissue;Umbilical Cord Blood;Umbilical Cord Blood Transplantation;vector;Work;Xenograft procedure

PROJECT_TITLE: Enhancing CAR T Cell Homing Through Glycoengineering


ADMINISTERING_IC: EB

ARRA_FUNDED: N

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

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

ORG_CITY: INDIANAPOLIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_FIPS: US

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE The development of innovative medical devices and technologies depends on a biomedical engineering workforce capable of identifying unmet clinical needs and working in teams to develop design solutions. Clinics in urban environments present unique health care issues, and this clinical immersion and team-based design program will challenge students to engage in engineering design in this context, with socioeconomic considerations in mind. The project will implement the novel INdiana Summer Clinical Residency in Innovation for Biomedical Engineers [(IN)SCRIBE] Program at Indiana University–Purdue University Indianapolis, in collaboration with the IU School of Medicine, to prepare biomedical engineering students for clinically-relevant, team-based design in an urban setting.

PI_NAMEs: HIGBEE, STEVEN J.;MILLER, SHARON JANELL (contact)

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: Academia;Achievement;Address;Affect;Area;Articulation;Awareness;Biomedical Engineering;Chronic Disease;Cities;Clinic;Clinical;clinically relevant;Collaborations;Communication;Complex;Death Rate;Decision Making;design;Development;Documentation;Education;Educational Curriculum;Engineering;engineering design;Environment;ethnic diversity;experience;Faculty;Health;health care delivery;health care disparity;Health Professional;Health Sciences;Healthcare;Human Resources;Immersion;improved;Indiana;Industry;Infant Mortality;innovation;Instruction;Knowledge;Legal patent;Literature;Medical;Medical Device;medical schools;Medical Technology;Medicine;Mentors;Mind;Mission;Modeling;multidisciplinary;novel;Nurses;Obesity;Organism;Patients;people of color;Persons;Physicians;Plague;Population;Positioning Attribute;Poverty;programs;racial diversity;real world application;Research;Research Personnel;Residencies;Resources;Rotation;Schools;Self Efficacy;skills;Smoking;social;social consciousness;Societies;socioeconomic disparity;Socioeconomic Factors;socioeconomics;student participation;Students;Technology;Training;Translating;Translations;undergraduate student;United States National Institutes of Health;Universities;Urban Health;urban setting

PROJECT_TITLE: A Clinical Immersion Program to Train Biomedical Engineers to Identify Indiana's Urban Health Needs


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Genetics;Hematology

ORG_CITY: BOSTON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: PROJECT NARRATIVE  Red blood cells are generated through a process of extreme terminal differentiation, whereby thousands of proteins are lost from the cell and replaced primarily by hemoglobin, which eventually constitutes ~98% of soluble protein. It has been a mystery how so many proteins could be eliminated from cells while specific proteins such as hemoglobin are preserved, but our recent work has implicated the protein modifier ubiquitin in this process, and in the proposed studies we will map this novel biological process by applying quantitative global proteomics and biochemical analysis to numerous mutants of ubiquitinating enzymes that are specifically induced in the late phase of red blood cell differentiation. These studies are providing a fundamental new perspective on cellular differentiation.

PI_NAMEs: FINLEY, DANIEL J (contact);FLEMING, MARK D

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: Actinin;Actins;Address;Anabolism;Automobile Driving;Binding;Biochemical;Biochemistry;Biological Process;Biology;Bypass;Cell Differentiation process;cell type;Cells;Cellular biology;Centrosome;Complex;crosslink;Crystallins;Crystallography;Cytoskeletal Modeling;Cytoskeletal Proteins;Cytoskeleton;Data;Development;dynactin;Dynein ATPase;Enzymes;Erythroblasts;Erythrocytes;Erythroid;Erythroid Cells;erythroid differentiation;Eukaryotic Cell;fiber cell;Generations;Genes;Genetic;genetic regulatory protein;Globin;Goals;Hemoglobin;Hydrogen;In Vitro;Informatics;interest;Lens Fiber;Leucine-Rich Repeat;Maps;Mass Spectrum Analysis;Mediating;Messenger RNA;Microscopy;Microtubules;milligram;Mitochondrial Proteins;Motor Activity;mRNA Translation;multicatalytic endopeptidase complex;Mus;mutant;Mutate;Myosin ATPase;novel;Phase;Physiological;Play;preservation;Process;programs;Proteasome Binding;protein crosslink;protein degradation;Proteins;Proteome;Proteomics;Radial;reconstitution;Regulatory Pathway;Reticulocytes;ribosome profiling;Ribosomes;Role;Signal Transduction;Specificity;Spectrin;structural biology;System;Testing;Time;transcriptome sequencing;transcriptomics;Translational Regulation;Translations;Tubulin;Ubiquitin;ubiquitin ligase;Ubiquitin Like Proteins;Ubiquitin-Conjugating Enzymes;Ubiquitination;Variant;Vesicle;Work

PROJECT_TITLE: Erythrocyte maturation through global remodeling of the proteome

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Suppression of anti-tumor immune response is a major mechanism facilitating the progression and therapeutic resistance of glioblastoma (GBM), the most malignant primary brain tumor. The objective of this project is to gain mechanistic insight into how differential accumulation and function of myeloid-derived suppressor cell (MDSC) subtypes in males versus females contribute to persistent GBM growth via suppression of local and systemic immunity, regulation of the complement system and re-programing the tumor microenvironment. The successful completion of this proposal will elucidate novel interventions targeting MDSC subset variation and account for sex as a biological variable for improved immunotherapy response, which will further be developed as part of my independent research program.

PI_NAMEs: BAYIK WATSON, DEFNE  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Accounting;Address;Adoptive Transfer;antagonist;anti-CTLA4;anti-PD-1;anti-tumor immune response;Attenuated;autocrine;Behavior;Blood Vessels;Bone Marrow;cancer stem cell;Cancer Vaccines;CAR T cell therapy;Cell Lineage;Cell Proliferation;Cells;chemotherapy;Chimera organism;Circulation;clinical efficacy;Clinical Trials;clinically relevant;Complement;complement system;density;Development;Disease;Disease Outcome;drug candidate;drug repurposing;efficacy evaluation;experimental study;Female;fludarabine;Foundations;Frequencies;Gene Expression Profile;Generations;genetic signature;Germ Cells;Glioblastoma;granulocyte;Growth;immune activation;immune checkpoint;Immune checkpoint inhibitor;Immune Evasion;Immune response;Immunity;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Impairment;improved;In Vitro;in vitro activity;in vivo;Incidence;Individual;Infiltration;inhibitor;insight;Interleukin-1 beta;Intervention;Knock-out;Laboratories;Left;male;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Mediator;monocyte;Mus;Myeloid-derived suppressor cells;neoplastic cell;novel;Oncolytic viruses;OX40;Pathogenesis;Pathway Analysis;Pathway interactions;Patient-Focused Outcomes;Patients;Peripheral;Pharmaceutical Preparations;pharmacologic;Phase;Play;polarized cell;Population Heterogeneity;Pre-Clinical Model;Predisposition;Primary Brain Neoplasms;Production;Prognosis;programs;receptor;Regulation;Reporting;Research;response;Role;Serum;sex;sex as a biological variable;Sex Differences;standard of care;stem cell self renewal;success;T-Cell Activation;T-Lymphocyte and Natural Killer Cell;Testing;Therapeutic;therapeutic target;therapy outcome;therapy resistant;transcriptome;treatment response;tumor;tumor growth;Tumor Immunity;tumor microenvironment;tumor progression;Tumor-associated macrophages;tumor-immune system interactions;tumorigenesis;Variant;women patients;women versus men

PROJECT_TITLE: Role of myeloid-derived suppressor cells in local and systemic immunosuppression in glioblastoma

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Transition to Independence Study Section (I)[NCI-I]


NIH_SPENDING_CATS: Autoimmune Disease;Cardiovascular;Orphan Drug;Rare Diseases;Scleroderma

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative Transforming growth factor beta2 (TGF-β2) is an important secreted protein that directs the proper development and functioning of the cardiovascular system. Disruption of TGF-β2 is associated with disorders such as Loeys-Dietz Syndrome Type 4, scleroderma, and Kawasaki disease that can cause severe defects in the heart and blood vessels. This grant will deepen our structural and biochemical knowledge of how TGF- β2 is activated in the body and will have broad implications for our understanding of these diseases while setting the stage for the development of new therapeutics.

PI_NAMEs: SPRINGER, TIMOTHY A (contact)

PROGRAM_OFFICER_NAME: CHARETTE, MARC F

PROJECT_TERMS: 2019-nCoV;Actins;Affinity;Antibodies;Aortic Aneurysm;Binding;Biochemical;Biological;Biological Process;Blood Vessels;cardiac repair;Cardiovascular Physiology;Cardiovascular system;Cell Line;Cell surface;Cells;Chimeric Proteins;cofactor;Complex;coronary fibrosis;Cryoelectron Microscopy;Crystallization;Crystallography;Cytoplasmic Tail;Cytoskeleton;Defect;Detection;Development;dimer;Dimerization;Disease;disulfide bond;extracellular;Extracellular Matrix;Family;Follow-Up Studies;Foundations;Grant;Growth Factor;Heart;Human;Integral Membrane Protein;Integrin Binding;Integrins;Knowledge;latent TGF-beta binding protein;Length;Loeys-Dietz Syndrome;LRRC32 gene;Mediating;member;Membrane;Modeling;Molecular Chaperones;Molecular Conformation;monomer;Mucocutaneous Lymph Node Syndrome;Mus;Mutagenesis;Mutate;Mutation;N-terminal;nanobodies;novel;novel therapeutics;Patients;Peptide Hydrolases;Peptides;Physiological;Pilot Projects;Preparation;prevent;Process;Protein Secretion;Rana;Reagent;receptor;repaired;Research;RGD (sequence);Role;Scleroderma;Serine Protease;Shapes;Site;Structure;Systemic Scleroderma;Testing;Therapeutic;therapeutic target;Time;Tissues;Transforming Growth Factor beta;Transforming Growth Factor Beta 2;Transforming Growth Factor beta Receptors;Vertebrates;Virus;X-Ray Crystallography

PROJECT_TITLE: Latent TGF-β2 Structure and Activation

STUDY_SECTION: MSFC

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


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

ORG_CITY: CLEVELAND

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE In cancer, arginine metabolism is often shunted into the pathways that produce polyamines, essential for cell growth and immuno-suppression; however, there is a critical gap in developing a method to correct arginine metabolism to suppress cancer growth. The proposed project aims to test whether sepiapterin, the naturally- occurring precursor of nitric oxide synthase (NOS) cofactor BH4, could normalize arginine metabolism to prevent breast cancer formation or enhance the efficacy of immunotherapy for breast cancer. The proposed project is relevant to public health because it will justify the use of sepiapterin as an adjuvant to immunotherapy or preventative agent for breast cancer.

PI_NAMEs: FURUTA, SAORI  (contact)

PROGRAM_OFFICER_NAME: VLAD, ANDA MIOARA

PROJECT_TERMS: Adjuvant;Adjuvant Therapy;Animals;antitumor effect;arginase;Arginine;Arginine decarboxylase;argininosuccinate lyase;argininosuccinate synthase;Breast;Breast Cancer Cell;Breast Cancer Prevention;cancer cell;cancer immunotherapy;cancer type;cell growth;Clinical Trials;cofactor;Drug resistance;efficacy evaluation;Enzymes;ERBB2 gene;FDA approved;Future;Glycine;Goals;Growth;Human;Immune;immunogenicity;Immunosuppression;Immunotherapy;improved;Incidence;innovation;Ligands;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Gland Parenchyma;Mammary Neoplasms;Measures;Mediating;Metabolic Diseases;Metabolic Pathway;Metabolism;Methods;mouse model;Mus;Nature;neoplastic cell;Nitric Oxide Synthase;novel;Ornithine Carbamoyltransferase;Ornithine Decarboxylase;Outcome;Pathway interactions;Phenylketonurias;Polyamine Synthesis Inhibition;Polyamines;prevent;Prevention;Production;programmed cell death ligand 1;Public Health;Reaction;Refractory;Reporting;Safety;sepiapterin;Shunt Device;side effect;systemic toxicity;Testing;tetrahydrobiopterin;Time;translational impact;tumor;tumor growth;tumor microenvironment;Tumor Promotion;Tumor Suppression;Tumor-associated macrophages;tumor-immune system interactions;Work

PROJECT_TITLE: Normalizing arginine metabolism with sepiaptein for immunostimulatory-shift ofHER2+ breast cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-Y(55)R]


ORG_CITY: WASHINGTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Currently, the vast majority of cancer single cell RNA sequencing (scRNA-seq) studies utilize cell-level gene expression to explore intratumorally heterogeneity. We propose to maximize the information gained from scRNA-seq data by integrating assessments of Single Cell-specific Expressed Single Nucleotide Variants (sceSNVs) with cell phenotypes, including gene expression, cell type, developmental stage, and cell fate. We will integrate recently developed by ours and other groups tools to correlate sceSNV expression to cell phenotypes and will catalog sceSNVs and their functional annotations in a public pan-cancer single cell Variome (scVariome) catalogue for community use.

PI_NAMEs: HORVATH, ANELIA  (contact)

PROGRAM_OFFICER_NAME: LI, JERRY

PROJECT_TERMS: Adrenal Glands;Adrenal Neuroblastoma;Alleles;analysis pipeline;Assessment tool;Automobile Driving;Bar Codes;Benchmarking;Biological;cancer cell;cancer type;Catalogs;Cell Line;cell type;Cells;Communities;Complement;Computer software;Data;data integration;Data Set;Deposition;Development;DNA;Embryo;experimental study;fetal;Gene Expression;Gene Expression Profile;Gene Frequency;genetic variant;Genetic Variation;Genomics;Germ Lines;Goals;improved;indexing;Individual;Knowledge;machine learning algorithm;Malignant Neoplasms;MCF7 cell;Metadata;Methods;Modeling;Mutation;neoplastic cell;novel;Outcome;Phenotype;Prevalence;Probability;prostate cancer cell;Reporting;Resources;RNA;RNA Splicing;Sampling;Single Nucleotide Polymorphism;single-cell RNA sequencing;stem;Time;tool;tumor;tumor heterogeneity;two-dimensional;Update;Variant;variant detection;variant of interest;Visualization

PROJECT_TITLE: scSNVariome - single cell SNVs driving cancer dynamics

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: AI

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BERKELEY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

ORG_STATE: CA

PHR: NARRATIVE The flavivirus genus contains many mosquito-borne human pathogens, including dengue, yellow fever, Zika, and West Nile viruses, that pose major public health threats but exhibit distinct tissue tropism and disease manifestations in infected humans, ranging from inapparent infections to severe and sometimes fatal disease. We recently demonstrated that flavivirus NS1 proteins mediate endothelial dysfunction and vascular leak in a tissue-specific manner reflecting the disease tropism of the distinct viruses. Using in vitro human endothelial cell systems, in vivo mouse models, and clinical samples from severe dengue and yellow fever patients, this proposal aims to identify and characterize host factors and viral NS1 determinants critical for NS1 cell binding, internalization, and signaling, which will improve our understanding of flavivirus pathogenesis and result in potential biomarkers for severe disease and novel viral and host therapeutic targets.

PI_NAMEs: HARRIS, EVA  (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Address;Affect;Animal Model;Binding;Biochemical;Biological;Biological Response Modifiers;Biology;biomarker identification;Blood;Blood - brain barrier anatomy;Blood Vessels;brain endothelial cell;Brazil;burden of illness;Cathepsin L;Cell Communication;Cells;Clathrin;Clinical;clinical investigation;Complement;cytokine;Data;Dengue;Dengue Fever;Dengue Virus;Deposition;dimer;Disease;emerging virus;Endocytosis;Endothelial Cells;endothelial dysfunction;Endothelium;enzyme pathway;Enzymes;Event;Exhibits;Family;Fatal Outcome;Flaviviridae;Flavivirus;Functional disorder;Genetic Techniques;Genomics;Glycobiology;Glycocalyx;heparanase;Human;human disease;human pathogen;improved;In Vitro;in vivo;Individual;Infection;Integration Host Factors;Intercellular Junctions;Intervention;Japanese encephalitis virus;Lipoproteins;Liver;Mediating;Medical;Membrane;Molecular;Molecular Virology;mosquito-borne;mouse model;Mus;mutant;Mutation;Neuraminidase;neurotropic;Nicaragua;Nonstructural Protein;novel;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patients;Polysaccharides;potential biomarker;Process;Production;Proteins;Public Health;receptor;Role;Sampling;Serum;severe dengue;Severity of illness;Signal Pathway;Signal Transduction;Specificity;Structural Biochemistry;structural biology;System;Testing;therapeutic target;tissue tropism;Tissues;Tropism;Variant;Vietnam;Viral;Viral Nonstructural Proteins;Virus;Virus Diseases;Virus Replication;West Nile virus;Work;Yellow Fever;Yellow fever virus;ZIKA;Zika Virus

PROJECT_TITLE: Host factors and viral determinants mediating flavivirus NS1 tissue-specific endothelial dysfunction and vascular leak

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Dental, Oral, and Craniofacial Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: ANN ARBOR

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Over 1,800,000 dental implants are placed in the U.S. annually, and by 2020, an expected 45,000,000 patients worldwide could benefit from at least one dental implant. Since bone quality is a key consideration for both short and long-term success of dental implants, new strategies of augmenting bone regeneration in the oral cavity are needed to support their use as the need continues to grow. Exosomes, a cell-secreted product containing bio-instructive molecules, show great promise in causing regeneration of bone and mineralized tissue when paired with an appropriate delivery platform, developed and validated in this proposal.

PI_NAMEs: SWANSON, WILLIAM BENTON (contact)

PROGRAM_OFFICER_NAME: FUQUA, CHANTEL FAYSAN

PROJECT_TERMS: 3-Dimensional;Attention;Biocompatible Materials;Biological;Biological Assay;biomaterial compatibility;Biomimetics;Blood Vessels;bone;bone healing;Bone Marrow;bone quality;Bone Regeneration;Bone Transplantation;Calcium;Calvaria;Cell Differentiation process;Cell secretion;Cell Separation;Cells;Cellularity;Clinical;Communication;controlled release;copolymer;craniofacial bone;craniofacial complex;Data;Defect;delivery vehicle;Dental Implants;Dentition;Denture Retention;differentiation in vitro;Disease;disease transmission;Edentulous Mouth;Elderly;Electron Microscopy;Electrophoresis;Encapsulated;Engineering;exosome;experimental study;fabrication;Gene Expression;Genes;Goals;Guided Tissue Regeneration;healing;Health;Histology;Implant;Implantation procedure;In Vitro;in vivo;in vivo Model;Infiltration;Inflammatory Response;invention;Kinetics;Laboratories;light scattering;Maxilla;mechanical properties;Mediating;Membrane Lipids;Mesenchymal Stem Cells;Messenger RNA;Methods;microCT;Microfluidic Microchips;MicroRNAs;Microspheres;mineralization;Modality;Molecular;molecular carrier;Morbidity - disease rate;Morphology;Mus;nanoindentation;Natural regeneration;Nature;novel;Oral cavity;Osteoblasts;Osteogenesis;osteogenic;Outcome;particle;Particle Size;Patients;Phenotype;Polymers;preservation;Proliferating;Property;Proteins;regenerative;Regenerative capacity;repaired;RNA;scaffold;Scanning Electron Microscopy;self assembly;Site;small molecule;Spectrometry;standard of care;stem cell differentiation;stem cell therapy;Stem cell transplant;Stromal Cells;submicron;success;Surface;technology validation;Therapeutic;Time;Tissue Engineering;Tissues;Trauma;Trehalose;Ultracentrifugation;Wound models

PROJECT_TITLE: Exosome-mediated Craniofacial Bone Tissue Engineering by Controlled Release

STUDY_SECTION: DSR

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]


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

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: PROJECT NARRATIVE Understanding the roles of distinct cell types in the pancreatic tumor microenvironment would inform on the complex biology of this intractable disease and help to identify potential strategies for therapeutic intervention. The studies proposed here will test the novel hypothesis that particular cells within healthy pancreas tissue known as stellate cells give rise to a tumor-promoting, functionally significant subset of the expansive fibroblast population of pancreatic tumors, and therefore represent a viable therapeutic target. Together, these studies will help us understand the mechanisms and consequences of pancreatic cancer stromal evolution, and may identify novel functions of these fibroblastic cells to be targeted for therapeutic benefit.

PI_NAMEs: SHERMAN, MARA H. (contact)

PROGRAM_OFFICER_NAME: BERA, TAPAN K

PROJECT_TERMS: Ablation;Acceleration;Address;Biology;cancer cell;Cancer Etiology;cell behavior;Cell Differentiation process;Cell Physiology;cell type;Cells;Cellular Metabolic Process;Cessation of life;chemotherapy;Clinic;Complex;Data;density;Desmoplastic;Development;Disease;disease phenotype;effective therapy;Epithelium;Evolution;experimental study;Extracellular Matrix;Fibroblasts;gain of function mutation;Gene Expression Profiling;Genetic;Genetic Transcription;Genotype;Goals;Heterogeneity;immune checkpoint blockade;immunoregulation;Immunotherapy;improved;in vivo;Inflammatory;Lipids;Malignant neoplasm of pancreas;Malignant Neoplasms;Minor;Modeling;mortality;mouse model;Mutation;neoplastic cell;novel;novel therapeutic intervention;novel therapeutics;Pancreas;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic neoplasm;pancreatic stellate cell;pancreatic tumorigenesis;Patients;pharmacologic;Phenotype;Population;Population Heterogeneity;Prognosis;programs;Proliferating;Property;rational design;Reaction;Regulation;Reporter;Reporting;Resistance;Role;Route;Sampling;Solid Neoplasm;Source;standard of care;stellate cell;Stromal Cells;targeted treatment;Testing;Therapeutic Intervention;therapeutic target;therapy resistant;Time;Tissues;TP53 gene;transdifferentiation;treatment response;tumor;tumor growth;Tumor Immunity;tumor microenvironment;tumor progression;Tumor Promotion;Tumor Tissue;Tumor Volume;United States;Work

PROJECT_TITLE: Origins and functions of pancreatic cancer-associated fibroblasts

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Bioengineering;Data Science;Endocrine Disruptors;Machine Learning and Artificial Intelligence;Maternal Health;Networking and Information Technology R&D (NITRD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_DEPT: PEDIATRICS

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE  Advances in high-resolution mass spectrometry (HRMS) offer unique opportunities to study the human exposome and the development of adverse health outcomes. Despite advances in non-targeted analysis, the number of confirmed chemicals remains fairly limited compared to the number of detected chemical features. The goal of this proposal is to develop novel computational methods to derive chemical structures and apply them to a large dataset of HRMS data from blood samples of pregnant women to study the influence of the exposome on pregnancy outcomes with a focus on preterm birth.

PI_NAMEs: ABRAHAMSSON, DIMITRI  (contact)

PROGRAM_OFFICER_NAME: CUI, YUXIA

PROJECT_TERMS: advanced analytics;Algorithms;Amino Acids;Analytical Chemistry;apprenticeship;Area;Award;Bile Acids;Binding;Bioinformatics;Biological;Biological Monitoring;Biometry;Birth;Blood specimen;California;Chemical Structure;Chemicals;Chemistry;Chlorobenzene;Clinical Data;cohort;Complement;computational chemistry;computer framework;computerized tools;Computing Methodologies;dashboard;Data;Data Analyses;data integration;Data Set;Development;developmental toxicity;Endocrine Disruptors;environmental chemistry;Environmental Exposure;Epidemiology;Equilibrium;Ethyl Ether;experience;exposed human population;Exposure to;feature detection;Flame Retardants;Fortification;Fundulus heteroclitus;Goals;Health;Human;Human Development;human disease;Hydrocortisone;in silico;Industrialization;innovation;insight;Knowledge;large datasets;Liquid Chromatography;Low Birth Weight Infant;Machine Learning;machine learning algorithm;Malignant Neoplasms;Mass Spectrum Analysis;Mentors;Metabolic Diseases;metabolome;metabolomics;Methods;molecular mass;Neurodevelopmental Disorder;novel;Octanols;Organic solvent product;Outcome;Pathway interactions;Persons;Pesticides;Plasticizers;Poly-fluoroalkyl substances;Postdoctoral Fellow;prediction algorithm;Pregnancy;Pregnancy Outcome;Pregnant Women;Premature Birth;prenatal;prenatal exposure;Property;psychologic;Race;Reading;reproductive toxicity;Research;Resolution;response;Risk Assessment;Sampling;Science;skill acquisition;skills;small molecule libraries;Stimulus;stressor;Structure;success;Sum;Term Birth;Time;time of flight mass spectrometry;tool;Toxicity Tests;Training;Umbilical Cord Blood;Visualization;Water;Work

PROJECT_TITLE: Non-target analysis of maternal and cord blood samples: Advancing computational tools and discovering novel chemicals

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Aging;Atherosclerosis;Bioengineering;Biomedical Imaging;Cardiovascular;Diabetes;Heart Disease;Heart Disease - Coronary Heart Disease;Obesity

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: PROJECT NARRATIVE The proposed study aims to provide the first evidence that after a heart attack, fat accumulation within injured heart tissue leads to impaired glucose utilization in healthy heart muscle. Furthermore, our goal is to use a novel imaging method that will provide reproducible and accurate assessment of glucose utilization in injured fatty hearts after treatment with antiallergic medications.

PI_NAMEs: ADER, MARILYN ;COKIC, IVAN  (contact);LI, DEBIAO

PROGRAM_OFFICER_NAME: SHANBHAG, SUJATA MADHUKAR

PROJECT_TERMS: Adipocytes;Adipose tissue;Aftercare;aged;Aging;Animal Model;Anti-Allergic Agents;Anti-Inflammatory Agents;atherogenesis;Attenuated;Cardiac;cardiac aging;Cardiomyopathies;Cell Degranulation;Cell membrane;Cholesterol;Chronic;Cicatrix;Coculture Techniques;Complex;Defect;Deposition;Diagnosis;Equilibrium;Event;Exhibits;Family suidae;Fatty acid glycerol esters;Fatty Acids;fluorodeoxyglucose;fluorodeoxyglucose positron emission tomography;Foam Cells;Glucose;Glucose Clamp;glucose disposal;Glucose Transporter;glucose uptake;Goals;Heart;Heart failure;Heart Injuries;High Prevalence;Hyperinsulinism;imaging approach;imaging modality;Impairment;improved;Infarction;Inflammaging;Inflammation;Inflammatory;Inflammatory Response;injured;Insulin;Insulin Resistance;insulin sensitivity;Ischemia;Link;Lipids;Loratadine;Macrophage;Magnetic Resonance Imaging;mast cell;Measurement;Metabolic;metabolic phenotype;Metaplasia;Methods;Modeling;Myocardial;Myocardial Infarction;Myocardial Ischemia;Myocardium;non-diabetic;non-invasive imaging;novel;novel therapeutic intervention;Obesity;oxidation;Pathologic;Patients;Pharmaceutical Preparations;Phase;Phenotype;physical inactivity;Play;porcine model;Positron-Emission Tomography;Predisposition;Process;Rattus;Reproducibility;Role;senescence;Sterility;Stress;Sudden Death;Tissues;uptake;Ventricular Remodeling

PROJECT_TITLE: Multiparametric PET/MRI Assessment of Mast Cell Stabilization Effects on Inflammaging and Glucose Utilization in Infarcted Myocardium

STUDY_SECTION: IGIS

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Biomedical Imaging;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Schizophrenia;Serious Mental Illness

ORG_CITY: BALTIMORE

ORG_DEPT: PSYCHIATRY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE This project aims to study a marker expressed by microglia, the resident immune cells in the brain, using a new imaging agent, [11C]CPPC. The availability of this microglial marker in the striatum and dorsolateral prefrontal cortex in brains of those with recent onset of schizophrenia and healthy controls will be compared. We will also assess the relationship between the microglial imaging marker and clinical signs characteristic of SZ.

PI_NAMEs: COUGHLIN, JENNIFER MARIE (contact)

PROGRAM_OFFICER_NAME: WIJTENBURG, SARAH ANDREA

PROJECT_TERMS: Ablation;Acute;Adolescence;Adult;Age;Animal Model;Astrocytes;Autoradiography;Back;Binding;Biological Models;Blood;Brain;Brain Diseases;Brain imaging;brain parenchyma;brain shape;brain tissue;Cell Communication;Cell surface;cell type;Cells;Characteristics;Clinical;Clinical Research;cognitive control;comparison control;Corpus striatum structure;Cross-Sectional Studies;cytokine;Data;Data Collection;Decision Making;design;Development;Diet;Disease;Dopamine;Down-Regulation;Drug Kinetics;Elements;Embryonic Development;Environmental Risk Factor;Extracellular Matrix;Functional disorder;Gene Expression Profile;Genes;Genetic;Genetic Models;Genetic Predisposition to Disease;glial activation;Glutamates;Hippocampus;Human;Image;imaging agent;imaging biomarker;Immune;immune activation;Immune response;Immunocompetent;Impaired cognition;Impairment;in vivo;Individual;Infiltration;Inflammation;Inflammatory;Interview;Learning;Lipopolysaccharides;Lymphocyte;Macrophage;Macrophage Colony-Stimulating Factor Receptor;Maintenance;Measures;Microglia;Modeling;molecular imaging;Monitor;Morphology;mouse model;Mus;neural circuit;neuroepithelium;neuroimaging;neuroinflammation;Neuronal Plasticity;Neurons;Neuropsychology;neurotransmission;nonhuman primate;offspring;Patients;Performance;Peripheral;pharmacologic;Phenotype;Population;Positioning Attribute;Positron-Emission Tomography;postnatal;Prefrontal Cortex;prenatal;presynaptic;Property;Proteins;Psychoses;Publishing;radiotracer;receptor;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Reporting;response;Role;Sampling;Schizophrenia;Short-Term Memory;Signal Transduction;Stress;Structure;Surface;targeted imaging;Temporal Lobe;Therapeutic;tool;Translational Research;translational study;trend;uptake;Validation;Viral;white matter

PROJECT_TITLE: Imaging microglial dysfunction in schizophrenia

STUDY_SECTION: NPAS

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


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: DETROIT

ORG_NAME: JOHN D DINGELL VA MEDICAL CENTER

PHR: Veterans, who were exposed to loud noise during training and while in theater, are more likely to experience dizziness, imbalance, and poor postural control. Vestibular organs transmit key information to central vestibular nuclei that control body position and movement in space as well as posture. Compromise of these critical cues for maintaining postural control and balance puts our Veterans at higher risk for falls as they age. Falls account for more than 50% of accidental deaths. Peripheral vestibular organs project to central vestibular nuclei responsible for transmitting signals for control of posture. Identifying and testing interventions for vestibular dysfunction in humans and in pre-clinical models requires central assessment tools, which are currently lacking in the field. We will examine differential noise effects on activity in vestibular central pathways while validating tools for future assessment of chronic effects.

PI_NAMEs: HOLT, AVRIL GENENE  (contact)

PROJECT_TERMS: Acceleration;Accidents;activity marker;Adult;Age;Animals;Assessment tool;auditory pathway;awake;Behavioral;body position;Brain;Brain region;Calcium;Cessation of life;Chronic;clinical application;Compensation;Complex;Cues;Data;Dizziness;Dose;equilibration disorder;Evoked Potentials;experience;Exposure to;fall risk;falls;FOS gene;Future;Genetic;Genetic Markers;Goals;Hair Cells;Head Movements;high risk;Histologic;Human;Immediate-Early Genes;In Vitro;in vivo;Intervention;Ions;Label;Labyrinth;Life;Literature;Loudness;Magnetic Resonance Imaging;Manganese;Measurement;Measures;Military Personnel;Movement;Musculoskeletal Equilibrium;Nature;Neuronal Differentiation;Neurons;Noise;noise exposure;noise trauma;Organ;otoconia;Pathologic;Pathology;Pathway interactions;Pattern;Perception;Peripheral;Physiological;Posture;Pre-Clinical Model;Rattus;Recording of previous events;Recovery;repaired;response;Rotation;Semicircular canal structure;Signal Transduction;Stimulus;Symptoms;Synapses;System;Testing;Time;tool;Training;transmission process;Trauma;Unsteady Gait;uptake;Vestibular dysfunction;Vestibular function;Vestibular nucleus structure;vestibular pathway;vestibular system;Veterans;Visualization

PROJECT_TITLE: MEMRI as an in vivo marker for changes in neuronal activity in central vestibular pathways

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


ORG_NAME: RLR VA MEDICAL CENTER

PHR: NARRATIVE  Chronic pain and disability after bone fracture is common. Approaches to pain management following orthopaedic surgery often include the use of opioids. We have identified a new targeted bone healing agent that may not only improve bone healing but may also decrease the associated pain. The latter could replace the necessity of opioids for pain management and serve as an important step in fighting the current opioid crisis.

PI_NAMEs: KACENA, MELISSA A (contact)

PROJECT_TERMS: Abdomen;Acceleration;Acute Pain;addiction;Afferent Neurons;angiogenesis;Attenuated;Behavior;Binding;Biological;Blood Platelets;bone;Bone callus;bone fracture repair;bone healing;Bone Marrow;Bone Morphogenetic Proteins;Bone Pain;Bone Regeneration;bone repair;C57BL/6 Mouse;cancer pain;CASP1 gene;Cell Lineage;cell type;Cells;Chest;Chimeric Proteins;Chronic;Chronic disability;chronic pain;Clinic;cytokine;disability;Drug usage;Endothelial Cells;Engineering;Family suidae;FDA approved;Female;fighting;Foundations;Fracture;Future;Growth Factor;healing;Health;Healthcare Systems;Hydroxyapatites;Immunohistochemistry;Impaired cognition;Impairment;improved;improved outcome;in vivo;Inflammasome;Inflammation;Inflammatory;inhibitor;Injury;Interleukin-1 beta;Lead;limb injury;Locomotion;Lower Extremity;Macrophage;male;Mechanics;Mediating;Mediator;Megakaryocytes;Modeling;Mus;musculoskeletal injury;nerve injury;Neuropathy;Nociception;Non-Steroidal Anti-Inflammatory Agents;novel;old mice;Operative Surgical Procedures;Opioid;opioid epidemic;Orthopedic Surgery;Osteitis;Osteoblasts;Osteogenesis;Pain;pain behavior;pain inhibition;Pain management;Patients;peptidomimetics;Pharmaceutical Preparations;pharmacologic;Phase;Platelet-Derived Growth Factor;platelet-derived growth factor BB;Platelet-Derived Growth Factor Receptor;Postoperative Pain;Postoperative Period;Prevention;Process;Production;progenitor;Rattus;Recombinants;Recovery;side effect;Signal Transduction;Site;skeletal;skeletal injury;spatiotemporal;surgical pain;Thrombopoietin;Transgenic Organisms;Translations;Trauma;Veterans

PROJECT_TITLE: Thrombopoietin Mimetic Peptides for Treatment of Fractures

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ENDB-P (01)]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Sleep Research

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative Older people sleep less, have more fragmented sleep, and nap more during the day, but the cause of these changes is not known. However, we now know that neurodegenerative processes deposit the hallmark proteins for Alzheimer’s disease (Abeta and phospho-tau), Parkinson’s disease (phospho-α-synuclein) and fronto-temporal lobe dementia (phospho-TDP-43) in neurons in the brain for many years before the neurological disorder can be diagnosed. We will investigate whether the aging changes in sleep are due to the deposition of these pathological proteins in neurons in the wake-sleep and circadian circuitry in the brain and may serve as a biomarker for these disorders.

PI_NAMEs: SAPER, CLIFFORD B (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: actigraphy;Address;Affect;Age;Aging;alpha synuclein;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease related dementia;Amyloid beta-Protein;Autopsy;Behavior;Behavioral;Biological Markers;Brain;Brain Stem;Cells;Cessation of life;Characteristics;circadian;Circadian Dysregulation;Circadian Rhythms;Clinical;Cognition;Cognitive;cohort;Data;demented;Dementia;Deposition;Diagnosis;Disease;Early identification;endophenotype;falls;Frontotemporal Dementia;Goals;Hour;hypocretin;Hypothalamic structure;Individual;Lewy Body Dementia;Life;Lobe;locus ceruleus structure;Measures;Memory;Napping;Nature;Nerve Degeneration;nerve supply;Nervous System Disorder;neurodegenerative dementia;Neurodegenerative Disorders;neuron loss;neuronal survival;Neurons;neuropathology;normal aging;Older Population;Optics;Parkinson Disease;Pathologic;Pathology;Patients;Pattern;Persons;Phase;Play;pre-clinical;preoptic nucleus;preservation;Process;prospective;protein TDP-43;Proteins;REM Sleep Behavior Disorder;Research;Rest;Role;Sampling;Sleep;Sleep disturbances;Sleep Fragmentations;sleep regulation;specific biomarkers;Structure;suprachiasmatic nucleus;symptomatology;synucleinopathy;tau-1;Testing;Time;tool;Validation;Vasopressins;Work;Wrist

PROJECT_TITLE: Wake-sleep Circuitry in Neurodegenerative Dementias

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Aging;Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Human Genome;Liver Disease

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: The incidence and prevalence of nonalcoholic fatty liver disease (NAFLD) are rapidly rising worldwide, but an effective pharmacotherapy is lacking. This project will apply state-of-the-art approaches to comprehensively characterize senescent hepatocytes that accumulate during NAFLD progression, uncover the underlying mechanisms for their senescence and determine whether targeting these mechanisms improves NAFLD. Successful complete of this study will provide the groundwork for future studies that exploit cellular senescence as a novel therapeutic strategy to treat liver diseases.

PI_NAMEs: DU, KUO  (contact)

PROGRAM_OFFICER_NAME: LOH, KATRINA SHUEH WEN

PROJECT_TERMS: Adult;adverse outcome;Age;Age related pathologies;aged;Aging;aging population;Animal Model;Area;Award;Bioenergetics;Bioinformatics;Biology;career;career development;Cell Aging;Cell Communication;Cell Death;Cell Line;Cell Reprogramming;cell type;Cells;Cellular Metabolic Process;Characteristics;Chemicals;chronic liver disease;clinically relevant;Coculture Techniques;Country;CRISPR library;CRISPR screen;Critical Pathways;cytotoxic;Data;Development Plans;disease model;Disease Progression;DNA Damage;Ensure;Epidemic;Etiology;F2R gene;Faculty;Fibrosis;Fluorogenic Substrate;Functional disorder;Future;Genes;genome editing;genome-wide;Goals;hallmarks of aging;Hepatocyte;hepatoma cell;Hepatotoxicity;Heterogeneity;high throughput screening;Histologic;Homeostasis;Human;Hydrolysis;immune cell infiltrate;Impairment;improved;Incidence;inhibitor;innovation;insight;Knowledge;Lead;Liver;Liver diseases;Liver Fibrosis;liver repair;Mediating;Mentored Research Scientist Development Award;Mentors;Mentorship;Metabolic;Metabolic syndrome;Molecular;Mus;non-alcoholic fatty liver disease;novel;novel strategies;novel therapeutic intervention;Nuclear RNA;Obesity Epidemic;old mice;overexpression;Oxidation-Reduction;Oxidative Stress;paracrine;Pathogenesis;Pathway interactions;Patients;Pharmacotherapy;Phenotype;Population;Positioning Attribute;Prevalence;prevent;Productivity;Proteomics;Records;release factor;Research;Research Personnel;Research Training;Resources;response;Rodent;Role;Scientist;screening;Seasons;senescence;senescent cell;senolytics;Senotherapy;Severities;single nucleus RNA-sequencing;skills;Sorting;stem cell expansion;System;Testing;Therapeutic;therapeutic target;Tissues;Training;transcriptome;transcriptome sequencing;wound healing

PROJECT_TITLE: Targeting Hepatocyte Senescence to Improve NAFLD

STUDY_SECTION: DDK

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


FUNDING_MECHANISM: OTHERS

ORG_CITY: PROVIDENCE

ORG_NAME: PROVIDENCE VA  MEDICAL CENTER

ORG_STATE: RI

PHR: This project will utilize clinical data from several hundred Veterans who have received and will receive transcranial magnetic stimulation (TMS) for depression as part of the nationwide “VA TMS Pilot Program” to develop a generalized model of TMS treatment response. This project will replicate and expand a nonlinear modeling approach of the TMS treatment response that we have developed using clinical data from our lab (n=97) as well as published group-level data from multiple large clinical trials of TMS. This nonlinear modeling approach uses an exponential decay function to quantify the magnitude, speed, and outcomes of TMS treatment response. This model provides a comprehensive characterization of the total TMS treatment course as well as an approach to predict treatment outcomes based on early response. This CDA2 will replicate and expand this work using the largest dataset of TMS response in Veterans to date and will yield precision psychiatry tools that would be widely applicable to many psychiatric interventions.

PI_NAMEs: BERLOW, YOSEF ALFRED (contact)

PROJECT_TERMS: Adoption;Algorithms;Award;Brain;Brain region;Caring;Clinical;Clinical Data;Clinical Trials;Data;Data Set;Databases;design;Development;disability;Early treatment;effective therapy;expectation;Feeling suicidal;Foundations;Goals;Individual;Infrastructure;instrument;Intervention;K-Series Research Career Programs;Literature;magnetic field;Major Depressive Disorder;Mathematics;Measurement;Measures;Mental Depression;Mentorship;Methods;Modeling;Monitor;neural network;neuropsychiatric disorder;neuroregulation;Non-linear Models;Nonpharmacologic Therapy;novel;Outcome;Pathologic;Patients;Pattern;pharmacologic;Pharmacological Treatment;Pharmacotherapy;Physicians;Physiologic pulse;Population;Post-Traumatic Stress Disorders;prediction algorithm;Prediction of Response to Therapy;Prognosis;programs;prospective;prospective test;Protocols documentation;Psychiatric therapeutic procedure;Psychiatry;psychosocial;Publishing;Questionnaires;reduce symptoms;Resistance;response;Scientist;side effect;Site;Software Tools;Specific qualifier value;Speed;Standardization;Symptoms;Techniques;Testing;Therapeutic;Time;tool;Training;Transcranial magnetic stimulation;treatment optimization;Treatment outcome;treatment pattern;treatment response;Veterans;Work

PROJECT_TITLE: Modeling the Treatment Response of Transcranial Magnetic Stimulation for Depression

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 MHBC-F (01)]


PHR: VA sleep medicine clinics exceeded 720,000 patient visits in 2018, and Veterans continue to have high rates of sleep disturbances and insomnia disorders. Rapidly expanding legislation in the U.S. has engendered widespread beliefs about cannabis’ therapeutic benefits, and Veterans often use cannabis for sleep despite equivocal evidence supporting its efficacy. Moreover, it remains uncertain which cannabis modes, formulations, or THC:CBD ratios are most harmful (or helpful) to sleep. This CDA-2 application will implement an innovative approach using different technologies to assess Veterans’ cannabis use and sleep over time, and in the natural environment. Results from this proposal and subsequent grants extending those findings will address a crucial knowledge gap concerning bi-directional links between cannabis, subjective sleep quality and sleep physiology (e.g., efficiency). Implications of this new knowledge cannot be overstated as sleep and several mental health issues common to Veterans (e.g., cannabis use disorder) are inextricably intertwined.

PI_NAMEs: BEREY, BENJAMIN LEONARD (contact)

PROJECT_TERMS: Acceleration;Address;Adherence;advanced analytics;Affect;Alcohols;Area;assessment application;Attention;Award;Behavior;Belief;Cannabidiol;Cannabinoids;Cannabis;cannabis administration;cannabis use behavior;career;Cellular Phone;Characteristics;Chronic;Clinic;Clinical;contextual factors;Data;design;Devices;Diagnosis;Dose;Drug Prescriptions;Ecological momentary assessment;Environment;experience;fitbit;fitness;Flowers;Formulation;Frequencies;Future;Goals;Grain;Grant;Health;Health behavior;ICD-9;Impairment;improved;Individual;innovation;Intervention;Interview;K-Series Research Career Programs;Knowledge;Laboratory Study;Link;Lived experience;marijuana use;marijuana use disorder;Measurement;Measures;Medical Marijuana;Medicine;Mental Health;Mentors;Mentorship;Methods;Observational Study;Outcome;Participant;Patient Self-Report;Patients;Perception;Personal Satisfaction;Phase;physical conditioning;Physiological Processes;Pilot Projects;poor sleep;Population;Post-Traumatic Stress Disorders;Prevention;Procedures;Productivity;programs;prospective;Protocols documentation;Public Health;Publishing;Quality of life;Random Allocation;Recommendation;recruit;Reporting;Research;Research Methodology;Research Personnel;Risk;Scientist;Services;skills;Sleep;sleep behavior;Sleep Disorders;Sleep disturbances;sleep health;sleep physiology;sleep quality;Sleeplessness;smartphone application;Smoke;Statutes and Laws;stem;Structure;substance use;Surveys;Techniques;Technology;Testing;Tetrahydrocannabinol;THC concentration;Therapeutic;Time;tool;Training;Training Activity;Traumatic Brain Injury;usability;vaporization;Veterans;Visit;Wakefulness;wearable device

PROJECT_TITLE: Applying Mixed Methods to Identify Links between Cannabis Use and Sleep Behaviors with Ramifications for Veterans Clinical Health Outcomes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURA-N (01)]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Therapeutics and Interventions;Depression;Dissemination and Implementation Research;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Lung;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Palliative Care;Post-Traumatic Stress Disorder (PTSD);Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health

PHR: Narrative Cardiorespiratory diseases are the most common causes of mortality and morbidity worldwide, including high rates of psychological distress symptoms (e.g., depression, anxiety, PTSD). Although symptomatic patients experience worse outcomes from their cardiorespiratory conditions, there are few interventions designed to address this problem at the population scale needed. This application is designed to test Blueprint, a self-directed mobile app-based intervention for psychological distress versus an Education Program control in a multicenter efficacy-focused clinical trial with specific targets for enrollment by race, ethnicity, gender, and Spanish spoken as a first language.

PI_NAMEs: COX, CHRISTOPHER ETHAN (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Acute Respiratory Distress Syndrome;Address;Adherence;Age;Anxiety;Behavioral;Black race;Characteristics;Clinical;Clinical Trials;clinically relevant;Cognitive Therapy;Colorado;community engagement;comparison control;Congestive Heart Failure;Coping Skills;COVID-19;COVID-19 pneumonia;Critical Illness;Data;depressive symptoms;design;disadvantaged background;Disease;Distress;Education;Educational Intervention;efficacy testing;Elements;Eligibility Determination;emotion regulation;Enrollment;Ensure;ethnic minority population;Ethnic Origin;experience;Failure;follow-up;future implementation;Gender;Health;health care delivery;health equity;Heterogeneity;Hispanic;Home;Hospitalization;Hospitals;Hybrids;implementation framework;implementation outcomes;Implementation readiness;improved;innovation;interest;Intervention;intervention delivery;Interview;Language;Lead;Mental Depression;Mental Health;Mental Health Services;Methods;mHealth;mobile application;Modeling;Morbidity - disease rate;mortality;Online Systems;Oregon;Outcome;Participant;patient population;Patients;Persons;physical symptom;Poly-fluoroalkyl substances;Population;Population Heterogeneity;Post-Traumatic Stress Disorders;preference;primary outcome;Problem Solving;programs;psychological distress;psychological symptom;Quality of life;Race;racial minority population;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Relaxation;Research;Research Priority;response;Sampling;Self Direction;Self Efficacy;Sepsis;Severity of illness;Site;skills;social;social factors;sociodemographics;Socioeconomic Status;Spanish;Spanish/English;Structure;Subgroup;success;Survivors;symptom management;symptom treatment;Symptoms;Telephone;Testing;therapy design;Time;Training Programs;treatment effect;Treatment Efficacy;treatment response;Work

PROJECT_TITLE: 1/2 Self-directed mobile adaptive coping skills intervention to improve psychological distress symptoms among cardiorespiratory failure survivors: the Blueprint RCT

STUDY_SECTION: CLTR

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


ORG_CITY: BEDFORD

ORG_NAME: EDITH NOURSE  ROGERS MEMORIAL VETERANS HOSPITAL

PHR: Older Veterans are more likely to die by suicide, as well as have more physical and cognitive challenges than the general population of the same age. Also, older Veterans with depression have major challenges that affect social involvement in their community, and connections with friends, and family. This can negatively affect their lives in many ways. VOICES Veterans Socials is a peer intervention in the community that creates weekly social groups for Veterans and has the potential to improve social functioning, mental health symptoms, and create lasting social support. These goals are consistent with the National Strategy on Reducing Military and Veteran Suicide, priority goal 4, addressing upstream risk and protective factors.

PI_NAMEs: GORMAN, JAY  (contact)

PROJECT_TERMS: Address;adverse outcome;Affect;Affective;Aftercare;Age;age effect;Applications Grants;Behavior;Behavioral;Belief;Buffers;Cessation of life;Cognitive;cognitive function;Collaborations;combat;Communities;community engagement;community setting;Consultations;cost effective;dementia risk;depressive symptoms;design;Development;Diagnostic;Elements;Eligibility Determination;Enrollment;Family;Feeling suicidal;follow up assessment;follow-up;Friends;Funding;Future;General Population;Goals;group intervention;guidebooks;Health;High Prevalence;human old age (65+);Impaired cognition;Impairment;improved;Individual;innovation;interest;Interpersonal Relations;Intervention;Interview;Life;Manuals;Measurement;Measures;meeting reports;meetings;member;Mental Depression;Mental Health;Military Personnel;military service;Modeling;Moods;mortality;novel;older adult;optimism;outreach;Participant;peer;peer support;Persons;physical conditioning;Physical Function;physical impairment;Pilot Projects;premature;prevent;protective effect;protective factors;psychological distress;randomized, clinical trials;recruit;Research;Retirement;Risk Factors;Role;Schedule;Self Efficacy;Services;Site;social;social contact;social engagement;Social Functioning;social group;Social Impacts;social interventions;Social isolation;Social support;Specialist;suicidal behavior;suicidal risk;Suicide;Suicide prevention;suicide rate;Symptoms;theories;Time;Training;Veterans;Well in self;Widowhood;Withdrawal

PROJECT_TITLE: VOICES Socials for Older Veterans with Depression


ADMINISTERING_IC: DA

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Drug Abuse (NIDA only);Gene Therapy;Genetics;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: Project Narrative There is an urgent need to develop new treatments for opioid use disorder. Here we propose to test an innovative new chemogenetic treatment strategy for opioid use disorder in mice. The proposed experiments will provide the proof-of-concept necessary to continue with further refinement of this technology in rats and eventually testing in nonhuman primates.

PI_NAMEs: SJULSON, LUCAS L (contact)

PROGRAM_OFFICER_NAME: NAIR, SUNILA GOPI

PROJECT_TERMS: addiction;adeno-associated viral vector;Adherence;Adult;Affect;Affinity;aged;Animal Model;Animals;Area;Behavior;Behavioral Paradigm;Binding;Brain;Buprenorphine;Cause of Death;Cocaine;Designer Drugs;Dopamine;Dopaminergic Cell;Drug usage;effective therapy;Effectiveness;Epidemic;experimental study;FDA approved;Fentanyl;Fiber;gene delivery system;Genetic;genetic approach;Goals;high reward;high risk;Human;ineffective therapies;Injections;innovation;Lead;Ligands;Measures;Methadone;Modeling;mu opioid receptors;Mus;nonhuman primate;novel;Nucleus Accumbens;Opioid;opioid use;opioid use disorder;Oral;Oxycodone;Patients;Peptides;Pharmaceutical Preparations;Phase II Clinical Trials;Photometry;Point Mutation;Procedures;Property;Psychological reinforcement;Public Health;Publishing;Rattus;receptor;Recording of previous events;Regimen;Research;Rewards;Self Administration;side effect;Structure;Technology;Testing;Therapeutic;Therapeutic Effect;treatment strategy;United States;Viral Vector

PROJECT_TITLE: Validating a novel chemogenetic strategy for opioid use disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 SKP-N (O1)]


ORG_CITY: MIAMI

ORG_NAME: MIAMI VA HEALTH CARE SYSTEM

PHR: Over 200,000 veterans suffer from chronic kidney disease, and nearly 30,000 of them already require dialysis to save their lives. Despite all technological and surgical advances, hemodialysis vascular access failure remains the primary source of hospitalization and complication, especially in veteran patients. This study identifies the molecules responsible for the most common vascular access failure in veterans, the arteriovenous fistula. Outcomes from these studies may represent a breakthrough that will provide new therapeutic targets and strategies to improve vascular access dysfunction, reduce medical complications, and ultimately save lives.

PI_NAMEs: VAZQUEZ PADRON, ROBERTO IRENARDO (contact)

PROJECT_TERMS: Aging;Anabolism;Anastomosis - action;Area;Arteriovenous fistula;Atlases;Autophagocytosis;Award;Basic Science;Biological;Biology;Blood flow;Blood Vessels;Cardiovascular system;cell type;Chronic Kidney Failure;Clinical;clinically relevant;cohort;Collagen;Complication;conditional knockout;Data;Deposition;Development;Dialysis procedure;discoidin domain receptor 1;Disease;ELK1 gene;End stage renal failure;Endothelial Cells;Etiology;experience;Experimental Animal Model;Extracellular Matrix;Failure;Fibrosis;Fistula;Functional disorder;Gene Expression;Gene Proteins;General Population;Genes;Genetic Transcription;Hemodialysis;Hospitalization;Human;Hyperplasia;improved;in vitro Model;in vivo;Injections;Knockout Mice;MADH3 gene;MAP Kinase Gene;Mediating;medical complication;Molecular;Morbidity - disease rate;Mus;MYH11 gene;new therapeutic target;Non-Fibrillar Collagens;novel therapeutics;Operative Surgical Procedures;Outcome;Outcome Study;Pathway interactions;Patients;personalized intervention;Phosphorylation;Physiologic arteriovenous anastomosis;Postoperative Period;prevent;Production;Proteins;Publishing;Research;Research Personnel;response;Retrospective cohort;Risk;Role;Sampling;Signal Transduction;single-cell RNA sequencing;Smooth Muscle Myocytes;Source;Spatial Behavior;Study models;Tamoxifen;Technology;Testing;therapeutic target;Time;Tissues;Transforming Growth Factor beta;Translational Research;United States;United States Department of Veterans Affairs;Venous;Veterans

PROJECT_TITLE: BCCMA: Cardiovascular Remodeling following Arteriovenous Fistula Creation: Type VIII Collagen Contributes to Adverse Arteriovenous Fistula Remodeling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 CARB-R (01)]


PHR: A crucial component of treatment success in HCC is early and appropriate diagnosis, currently done via CT/ MRI scans with or without biopsy. We propose a new way to enhance the detection and accuracy of staging of HCC, by using PSMA PET in addition to standard CT/MRI, in three different clinical settings (surveillance, untreated, and previously treated veterans). We anticipate that PSMA PET will improve HCC detection in indeterminate lesions, enable additional visualization of entire tumors in a more functional manner, and decrease reliance on invasive and limited biopsies. The overall impact of the study is to enhance treatment capabilities by decreasing time to initiation of therapy based upon improved detection of HCC or potential HCC by using PSMA PET and early initiation of systemic therapy in patients with otherwise undetectable metastases.

PI_NAMEs: JOHN, BINU  (contact)

PROJECT_TERMS: Abdomen;Ablation;Accounting;Aftercare;Alcoholic Liver Diseases;Antigen Targeting;Biology;Biopsy;Cancer Etiology;Cause of Death;Cessation of life;Cirrhosis;Clinic;Clinical;Clinical Research;Clinical Trials;contrast enhanced computed tomography;Data;Detection;Diagnosis;diagnostic accuracy;Diagnostic Neoplasm Staging;Disease;Distant;Distant Metastasis;Dose;Early Diagnosis;Emission-Computed Tomography;Evaluation;Extrahepatic;fluorodeoxyglucose;FOLH1 gene;Future;Healthcare Systems;Hepatitis C;Image;improved;In complete remission;Incidence;Infection;innovation;intrahepatic;Label;Lesion;Liver;Liver diseases;Longitudinal Studies;lymph nodes;lymphadenopathy;Magnetic Resonance Imaging;Malignant neoplasm of liver;Malignant neoplasm of prostate;Malignant Neoplasms;men;Methods;military veteran;Monitor;MRI Scans;Neoplasm Metastasis;Newly Diagnosed;Nodule;non-alcoholic fatty liver disease;novel;Observational Study;patient population;Patients;Positron-Emission Tomography;precision oncology;Primary carcinoma of the liver cells;Prognosis;prognostic indicator;Property;Provider;Radiogenomics;randomized, clinical trials;Recommendation;Residual Neoplasm;Residual state;response;Risk;Role;Sensitivity and Specificity;serial imaging;Specificity;Staging;standard of care;statistics;success;Systemic Therapy;Testing;Time;Tracer;treatment response;tumor;United States;uptake;Veterans;Viral hepatitis;Visualization;X-Ray Computed Tomography

PROJECT_TITLE: Addition of F18-Piflufolastat PET/CT to Cross-Sectional Imaging for the Staging and Management of Hepatocellular Carcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCC-S (01)]


NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

ORG_CITY: SAN FRANCISCO

ORG_NAME: J. DAVID GLADSTONE INSTITUTES

PHR: RELEVANCE (See instructions): The proposed research is relevant to public health because it will determine if and how new acetyl-lysine  reader proteins sBET and RPRD1 control HIV latency. These results will improve the understanding of the  basic biology of HIV latency and will, ultimately, inform the development of new therapies to reverse HIV  latency in infected individuals. This project supports the NIH’s mission and aligns with one of its high-priority topics of research that awards AIDS-designated funds to support research toward a cure for HIV.

PI_NAMEs: OTT, MELANIE MARIA (contact)

PROGRAM_OFFICER_NAME: MCDONALD, DAVID JOSEPH

PROJECT_TERMS: Acetylation;Acetyltransferase;Acquired Immunodeficiency Syndrome;Award;Binding;Biology;Bromodomain;C-terminal;Cells;chromatin immunoprecipitation;Chromatin Remodeling Factor;Clustered Regularly Interspaced Short Palindromic Repeats;Co-Immunoprecipitations;cofactor;Complex;CRISPR interference;Data;Deposition;Development;DNA;DNA Damage;DNA Double Strand Break;DNA-Directed RNA Polymerase;Drug Targeting;ds-DNA;Endogenous Retroviruses;Ensure;Epidemic;Event;experimental study;Funding;Gene Expression;Gene Silencing;Genetic Transcription;Genome;Goals;Health;Histones;HIV;HIV Infections;Hybrids;improved;Individual;induced pluripotent stem cell;insight;Instruction;Integrase;Integration Host Factors;Invaded;Investigation;Journals;knock-down;Life;Location;Lysine;Maintenance;Methyltransferase;Microbiology;Mission;Modeling;Modification;Molecular;Monitor;Mutagenesis;Nature;new therapeutic target;novel;novel therapeutics;Nuclear;Nucleosomes;Polymerase;Positioning Attribute;prevent;Process;Productivity;programs;promoter;Protein Isoforms;Proteins;Provirus Integration;Proviruses;Public Health;Publishing;Reader;recruit;Regulation;Reporting;Repressor Proteins;Research;Research Support;Retroviridae;RNA;RNA Polymerase II;Role;Site;T-Cell Activation;targeted nucleases;Testing;Therapeutic;therapeutic target;Transcription Elongation;Transcription Initiation Site;United States National Institutes of Health;Viral;virology;Virus;Virus Integration

PROJECT_TITLE: Role of Factor Acetylation in the Regulation of HIV Transcription


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

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: RELEVANCE (See instructions): A major obstacle to rational HIV-1 vaccine design is the lack of an outbred primate animal model where  the induction of broadly neutralizing antibodies (bNAbs) can be achieved in a consistent and reproducible manner.  This application proposes proof-of-concept preclinical immunogenicity and protection studies in rhesus  macaques, which will test the ability of novel germline-targeted CAP256 Env based priming immunogens,  together with lineage based as well as V2 apex SET designed boosting immunogens, to elicit V2 apex bNAbs  that protect monkeys from a heterologous tier 2 virus challenge.

PI_NAMEs: HAHN, BEATRICE H (contact)

PROGRAM_OFFICER_NAME: MALASPINA, ANGELA

PROJECT_TERMS: Affinity;Animal Model;Animals;Antibodies;Antibody Response;Antibody-mediated protection;Antigens;Apical;Autologous;B-Cell Receptor Binding;B-Lymphocytes;Binding;bioinformatics tool;booster vaccine;breakthrough infection;CD4 Positive T Lymphocytes;Cell Lineage;Characteristics;COVID-19;Data;design;Development;Dose;env Glycoproteins;Epitopes;Event;Evolution;Genes;Germ Lines;Goals;HIV;HIV vaccine;HIV-1;HIV-1 vaccine;Human;Immunization;Immunize;immunogenicity;improved;in vivo;Infection;Instruction;lipid nanoparticle;Macaca;Macaca mulatta;Maps;Masks;member;Membrane;Messenger RNA;Monkeys;Monoclonal Antibodies;neutralizing antibody;neutralizing monoclonal antibodies;novel;Nucleosides;Paper;Pathway interactions;Pattern;Polysaccharides;pre-clinical;Primates;Productivity;Property;protective efficacy;Publishing;rational design;Regimen;Reproducibility;response;Rhesus;simian human immunodeficiency virus;Testing;Translating;transmission process;Vaccination;Vaccine Design;vaccine development;Vaccine Research;Vaccines;Variant;vector;Virus;Work

PROJECT_TITLE: Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative Cerebral amyloid angiopathy (CAA) is one of the leading causes of symptomatic intracerebral hemorrhage (ICH) in the elderly, and bleeding from the leptomeningeal vasculature has recently been implicated in the pathophysiological mechanisms underlying CAA-related ICH. The proposed research will use a multimodal approach combining neuropathological analysis of human tissue and in vivo imaging of mouse models to investigate the causes and consequences of leptomeningeal bleeding in CAA. This project has the potential to uncover novel, and much-needed, therapeutic targets for the prevention of CAA-related ICH.

PI_NAMEs: KOZBERG, MARIEL GAILEY (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: abeta deposition;Acute;Amyloid beta-Protein;Animal Model;Area;Attention;Award;Blood;Blood - brain barrier anatomy;blood product;Blood Vessels;Brain;brain tissue;career;career development;Cerebral Amyloid Angiopathy;Cerebral hemisphere hemorrhage;Cerebrospinal Fluid;Cerebrovascular system;Chronic;Clinical;clinical diagnosis;Cortical vasculature;Data;deep learning algorithm;Deposition;Detection;Development;Development Plans;effective therapy;efficacy evaluation;Elderly;Environment;Evaluation;Event;experience;experimental study;Extravasation;Future;General Hospitals;Goals;Hemorrhage;Human;human tissue;improved;in vivo;in vivo imaging;in vivo optical imaging;Inflammation;Inflammation Mediators;Inflammatory;inflammatory marker;Inherited;Injury;interdisciplinary approach;International;Knowledge;knowledge base;Lead;Leptomeninges;Lesion;Link;Lobar;Macrophage;Magnetic Resonance Imaging;Massachusetts;Mediating;medical schools;Mentors;Mentorship;Microscopic;Microvascular Dysfunction;Modeling;mouse model;multimodality;multiphoton microscopy;Mutation;neuroinflammation;Neurology;neuropathology;new therapeutic target;novel;optical imaging;Pathology;Patients;Penetration;Prevention;Process;Recurrence;Research;Resources;Risk;Risk Factors;Rodent Model;Rupture;Safety;Sampling;Scientist;Secondary to;Siderosis;Sporadic Cerebral Amyloid Angiopathy;Stroke;Subarachnoid Hemorrhage;Subarachnoid Space;symposium;therapeutic target;Time;tissue injury;Tissues;Training;Vascular Diseases;vascular inflammation;vascular injury;Vascular remodeling;Work

PROJECT_TITLE: Causes and Consequences of Leptomeningeal Bleeding in Cerebral Amyloid Angiopathy

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-B (02)]


ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: PROJECT NARRATIVE The current paradigm of autosomal dominant polycystic kidney disease (ADPKD) pathogenesis is based on progressive renal cysts growth over the patient's life, with the most prominent cysts being those that emerged in utero. However, data obtained with our new lab-made image analysis tools show that individual cysts' growth is a dynamic process with highly variable cysts' growth rates that change over time. Therefore, we plan to provide mechanistic insight into the pathobiology of cysts formation’s dynamic and regression phases using a model of injury-induced cystogenesis in our new Pkd2K874A*1/+ rat (with and without C3 complement deficiency) and complement these studies with single-cell and spatial transcriptomics.

PI_NAMEs: MRUG, MICHAL  (contact)

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Affect;Age;Alleles;Animal Model;Animals;Autosomal Dominant Polycystic Kidney;Biological Markers;Birth;Cells;Child;Clinical;Clinical Trials;cohort;Complement;complement deficiency;Complex;Cyst;Cystic kidney;Data;Defect;Development;Diagnosis;Disease;disease classification;Disease Progression;Early identification;End stage renal failure;Exclusion;FDA approved;Foundations;Future;Genes;genetic variant;Goals;Growth;Heterozygote;high risk;Human;Image;Image Analysis;Imaging Techniques;improved;in utero;indexing;Individual;Injury;insight;Intervention;Kidney;Kidney Diseases;Knock-out;Life;Magnetic Resonance Imaging;Mediating;Modeling;Monitor;mouse model;Mus;novel;Outcome;outcome prediction;Pathogenesis;Pathogenicity;Pathway interactions;Patients;pediatric patients;Phase;Phenotype;PKD1 gene;PKD2 gene;Process;Proteins;rate of change;Rattus;Reperfusion Injury;Research;Risk Assessment;Role;Staging;Testing;Therapeutic;Therapeutic Intervention;Time;time interval;tool;transcriptomics;Transplantation;Veterans;virulence gene

PROJECT_TITLE: Role of complement in injury-induced cystogenesis among carriers of a single ADPKD gene defect

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NEPH-N (01)]


ORG_CITY: MADISON

ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

ORG_STATE: WI

PHR: Veterans are at increased risk for cholangiocarcinoma (CCA)—a type of liver cancer—due to their advanced age and increased incidence of hepatitis C virus and chronic liver disease. Despite the use of systemic chemotherapy, CCA is deadly with a 5-year survival of 10% in the advanced setting. Recent work has defined distinct molecular subtypes of CCA, however tuning precision strategies for an individual remains limited to a few select biomarkers and chemotherapy remains a standard of care, despite significant clinical toxicities. I hypothesize that cyclin-dependent kinase 7 (CDK7) regulates response to DNA damage after chemotherapy in patient-derived organoid and xenograft models of CCA. By characterizing the mechanism of this response in combination with chemotherapy, we can develop biologically informed combination therapy. Together, this project utilizes human models of CCA to better understand both therapeutic sensitivities and resistance mechanisms to inform rational strategies to improve the survival of Veterans with this devastating disease.

PI_NAMEs: KRATZ, JEREMY DAVID (contact)

PROJECT_TERMS: advanced disease;American;Apoptosis;biliary tract;Biological Assay;biomarker selection;Cancer Biology;Cancer Etiology;cancer stem cell;career;career development;Cell Cycle;Cell Cycle Arrest;chemotherapy;Cholangiocarcinoma;chronic liver disease;Cisplatin;Clinical;Clinical Management;clinical predictors;clinical translation;Colorectal Cancer;Combination Drug Therapy;Combined Modality Therapy;Core Facility;Cyclin-Dependent Kinases;Cytotoxic Chemotherapy;Data;Dedications;Developmental Therapeutics Program;Diagnosis;Disease;DNA Damage;DNA Repair;Down-Regulation;educational atmosphere;Educational workshop;Elderly;Environment;epigenomics;Equipment;experience;Expression Profiling;Flow Cytometry;Fluorescence Microscopy;Funding;Gamma-H2AX;gemcitabine;Genetic Transcription;genomic data;Genomics;Goals;Growth;Health;Hepatitis C Incidence;hepatobiliary cancer;Histologic;homologous recombination deficiency;human model;Image;Immunofluorescence Immunologic;improved;in vivo;in vivo Model;Individual;Induction of Apoptosis;Inferior;inhibitor;Institution;Internal Medicine;Investigation;Knowledge;Laboratories;Lead;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of liver;Malignant Neoplasms;Mediating;Mediator;Medical Oncologist;Medical Oncology;medical schools;Medical Staff;Medicine;Mentors;Mentorship;Michigan;Microscopy;military veteran;Modeling;Molecular;molecular subtypes;mortality;Mus;Necrosis;new therapeutic target;Non-Malignant;novel;oncology program;Organ;Organoids;Outcome;overexpression;oxaliplatin;Pathologic;Pathway interactions;patient derived xenograft model;Patients;Phosphorylation;Physicians;post-doctoral training;Pre-Clinical Model;precision oncology;predict clinical outcome;Prediction of Response to Therapy;professor;prognostic;programs;prospective;Public Health;recruit;Research;Research Project Grants;Resistance;resistance mechanism;Resources;response;Risk;RNA Polymerase II;Sampling;Scientist;Signal Pathway;skills;Solid;spheroids;standard of care;Standardization;stem cell model;targeted treatment;Testing;Therapeutic;therapy resistant;Time;Tissues;tool;Toxic effect;Training;Transcriptional Regulation;transcriptome sequencing;Translational Research;treatment response;tumor;United States;United States Department of Veterans Affairs;Universities;Veterans;Veterans Hospitals;Western Blotting;Wisconsin;Work;Xenograft Model

PROJECT_TITLE: Defining Therapeutic Sensitivity of Patient-Derived Cancer Organoids in Cholangiocarcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCB-A (01)]


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

PHR: The purpose of this application is to develop sensitive imaging agents for pan-amyloid beta species of Alzheimer’s disease. The proposed studies will provide beneficial information for the drug development for Alzheimer’s disease.

PI_NAMEs: RAN, CHONGZHAO  (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: AD transgenic mice;Affinity;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Alzheimer’s disease biomarker;Amino Acids;Amyloid beta-Protein;analog;Animal Model;APP-PS1;Appearance;Binding;Biological Markers;Brain;brain tissue;Categories;Clinical;computational chemistry;cost efficient;Cryoelectron Microscopy;Data;Deposition;design;Detection;Development;Diagnosis;Docking;drug development;Early Diagnosis;FDA approved;first-in-human;Future;Generations;Human;Hydrophobicity;imaging agent;imaging study;In Vitro;in vivo;Institutional Review Boards;Isotopes;Label;Libraries;Ligands;Measurement;Measures;Methods;Modeling;Molecular;Monitor;mouse model;Mus;National Institute on Aging;Neurologic;neurotoxic;nonhuman primate;optimism;Pathology;Penetration;Positron-Emission Tomography;Preventive;Preventive treatment;Publishing;Quantitative Structure-Activity Relationship;Radiochemistry;Research;screening;Series;Slice;Slide;Stains;Structure;Symptoms;Syndrome;tau Proteins;Testing;Tracer;Transgenic Organisms;translational study;uptake;urinary gonadotropin fragment

PROJECT_TITLE: Development of sensitive PET tracers of pan-Amyloid-beta species for Alzheimer's disease

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


ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA CITY VA MEDICAL CENTER

ORG_STATE: OK

PHR: The demographics of the veteran population clearly demonstrate that illnesses afflicting the elderly are a major concern of the Department of Veterans Affairs. Currently, the number of veterans over 50 years of age represents over 70% of the total veteran population. Research has shown that chronic, low-grade inflammation increases dramatically with age and that inflammation is a major risk factor for a variety of age- related diseases that affect elderly veterans, especially neurogenerative diseases like Alzheimer's disease. The research in this application will study a novel mechanism involved in neuroinflammation: the activation of necroptosis specifically in neurons is proposed to induce the release of necroptotic extracellular vesicles from neurons that activate microglia and astrocytes leading to neuroinflammation, which results in neuronal dysfunction and reduced cognition. Data from this project has the potential of leading to new therapies to treat neurodegeneration and the loss of cognition that occurs with age in elderly veterans.

PI_NAMEs: FREEMAN, WILLARD M;RICHARDSON, ARLAN G. (contact)

PROJECT_TERMS: Adult;Affect;Age;age related;Age Years;age-related disease;Aging;aging brain;aging related;Alzheimer's Disease;Astrocytes;Attenuated;Binding;Brain;Brain region;Calcium;Cell Culture Techniques;Cell Death;Cell membrane;cell type;Cells;Cessation of life;chemokine;Chronic;Cognition;conditioned fear;cytokine;Cytolysis;Data;demographics;Disease;Elderly;experimental study;extracellular vesicles;Gene Expression;Generations;Grant;hallmarks of aging;Hippocampus;Immune;Impaired cognition;improved;Induced Neurons;Inflammaging;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;Knock-in Mouse;Knockout Mice;Knowledge;Link;Long-Term Potentiation;Measures;Microglia;military veteran;Molecular;Morbidity - disease rate;morris water maze;mortality;mouse model;Mus;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;neuron loss;Neuronal Dysfunction;Neurons;novel;novel therapeutics;object recognition;old mice;overexpression;Pathway interactions;Pattern;Phosphorylation;Population;prevent;Research;response;RIPK1 gene;RIPK3 gene;Risk Factors;Role;Rupture;single-cell RNA sequencing;Slice;Stimulus;targeted treatment;Testing;Time;Tissues;transcriptome;transcriptomics;Transgenic Mice;Transgenic Organisms;United States Department of Veterans Affairs;Veterans;Wild Type Mouse

PROJECT_TITLE: Does Necroptosis Play A Role in Inflammation And Aging?

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURD-E (01)]


NIH_SPENDING_CATS: Biotechnology;Endocrine Disruptors;Genetics;Human Genome;Lead Poisoning;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Social Determinants of Health;Women's Health Research

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Environmental exposures to metals (e.g., lead) early in life have long-term adverse health effects, partly due to dysregulated epigenetic reprogramming that includes genomic imprinting. The proposed study seeks to investigate molecular mechanisms governing genomic imprinting following early life lead exposure by characterizing sex-, tissue-, and developmental stage-specific imprinted gene dysregulation. Evaluation of exposure-relevant mechanisms during gestation will elucidate toxicoepigenetic reprogramming by fetal sex to lay the groundwork for potential interventions.

PI_NAMEs: PERERA, BAMBARENDAGE PINITHI UPEKKA (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: adverse outcome;adverse pregnancy outcome;Age;Alleles;Animals;Automobile Driving;Bioinformatics;Biological Markers;Birth;bisulfite sequencing;blood lead;Brain;Child;Collaborations;Conceptions;Core Facility;critical period;Dangerousness;Data;Data Analyses;Defect;Development;developmental toxicology;Disease;disorder risk;DNA Methylation;Educational process of instructing;Embryo;Embryonic Development;Ensure;Environment;Environmental Exposure;Epigenetic Process;epigenome;Evaluation;exposed human population;Exposure to;Female;fetal;Fetal Growth;Fetal Tissues;Foundations;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Genomic Imprinting;Goals;Grant;Growth;Health;histone modification;House mice;Human;human disease;Hybrids;imprint;in utero;Intervention;Investigation;Knowledge;Laboratories;Lead;lead exposure;Lead levels;Lead Poisoning;Leadership;Life;Link;Literature;Maps;Mentors;Mentorship;Metal exposure;Methods;Michigan;Modeling;Molecular;Morphology;mouse model;multidisciplinary;Mus;neurodevelopment;neurotoxic;old mice;Outcome;Parents;Partner in relationship;Pathology;Pattern;Perinatal;Perinatal Exposure;Phenotype;Placenta;placental mammal;Population;Predisposition;Pregnancy;pregnant;Pregnant Women;prenatal exposure;programs;Regulation;Research;sex;Sex Differences;sex-specific imprints;Single Nucleotide Polymorphism;skills;success;Tissues;Toxic effect;Toxic Environmental Substances;toxicant;Toxicant lead;Toxicology;Training;transcriptome sequencing;Universities;Untranslated RNA;whole genome

PROJECT_TITLE: Imprinted Gene Regulation by in utero Lead Exposure in Mice

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 BWD-D (KS)]


NIH_SPENDING_CATS: Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Lung;Prevention;Sleep Research;Social Determinants of Health

ORG_CITY: TUCSON

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative. Existence of disparities in health in disadvantaged populations in the country is a major problem. The lack of sufficient diverse representation among researchers and scientists who work on lung, sleep, and pandemic related consequences on lung and sleep problems has become a critical and urgent challenge. Our proposed training program is designed to help address these problems by increasing the number of well-trained early career faculty from institutions across the country that will be positioned to contribute to research geared to resolve health and healthcare disparities in the area of lung, sleep, and pandemic consequences to lung and sleep conditions and thereby promote health equity.

PI_NAMEs: MORENO, FRANCISCO A;NIKOLICH, JANKO Z.;PARTHASARATHY, SAIRAM  (contact)

PROGRAM_OFFICER_NAME: DIXIT, SHILPY

PROJECT_TERMS: Acute;Address;Affect;Area;Arizona;Attention;Biomedical Research;career;career development;Community based prevention;Country;COVID-19 pandemic;design;didactic education;Disparity;Disparity population;early-career faculty;Education;education research;Eligibility Determination;Environment;experience;Faculty;Funding;Funding Mechanisms;Goals;Grant;Health;health care disparity;health difference;health disparity;health equity;health equity promotion;Health Promotion;Healthcare;Home;Individual;Infrastructure;innovation;Institution;interest;knowledge base;Latino;Leadership;Link;long-term sequelae;Lung;Manuscripts;Mentors;Methodology;minority communities;Minority-Serving Institution;Mission;National Heart, Lung, and Blood Institute;Native Americans;pandemic disease;peer;Population;Positioning Attribute;Post-Acute Sequelae of SARS-CoV-2 Infection;Postdoctoral Fellow;Preparation;Productivity;programs;Qualifying;recruit;Reduce health disparities;Research;Research Personnel;Research Project Grants;Research Training;Respiratory Failure;responsible research conduct;Science;Scientist;skill acquisition;skills;Sleep;Sleep Apnea Syndromes;Sleep Disorders;Statistical Methods;success;summer institute;System;Time;Training;training opportunity;Training Programs;translational applications;translational approach;Underrepresented Populations;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Translational Approaches to Health Disparities in Lung, Sleep, and Pandemics

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-G (O2)]


ORG_CITY: ANN ARBOR

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Cryptococcus is a ubiquitous fungal pathogen that causes substantial morbidity and mortality in Veterans and other patients. Veterans have an increased risk of infection due to higher rates of immunocompromising medical conditions relative to the general population. Current therapies for patients infected with Cryptococcus are lengthy, highly toxic, often ineffective, and may contribute to inflammatory complications linked to pathological tissue damage, mortality, and/or the development of lasting disabilities in these patients. Antibody immunotherapies neutralizing targeted pathways already have revolutionized the treatment of autoimmune diseases and some types of leukemia, through their specificity allowing for the elimination of a single immune factor which has a causal role. This validation study will test the effectiveness of anti-CXCR3 antibody treatment in limiting detrimental immune responses during cryptococcal CNS infection using a mouse model of cryptococcal meningitis and promises to create much safer alternative to the existing treatment.

PI_NAMEs: OLSZEWSKI, MICHAL A (contact)

PROJECT_TERMS: Address;Adrenal Cortex Hormones;Adverse effects;Amphotericin B;anti-fungal agents;Antibodies;antibody immunotherapy;Antibody Therapy;Antifungal Therapy;Antiinflammatory Effect;Autoimmune Diseases;Brain;Brain Injuries;Cells;Central Nervous System;Central Nervous System Infections;central nervous system injury;Cessation of life;chemokine;Clinical Trials;Cryptococcal Meningitis;Cryptococcosis;Cryptococcus;Cryptococcus neoformans;Cryptococcus neoformans infection;CXC chemokine receptor 3;CXCR3 gene;Data;Deterioration;Development;disability;Disease;Dose;effectiveness testing;Fluconazole;fungus;Gene Deletion;General Population;Goals;Human;Immune;Immune response;Immunity;Immunocompromised Host;Immunologic Factors;immunopathology;Immunotherapy;Impairment;Infection;infection risk;Inflammation;Inflammatory;Inflammatory Response;Intercept;Intervention;leukemia;Link;Liposomes;Mediating;Medical;Meningoencephalitis;microbial;Modeling;Monoclonal Antibody Therapy;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;Names;Nerve Degeneration;Nervous System Trauma;neuroinflammation;Neurologic;Neurologic Symptoms;neuron apoptosis;Neurons;novel;Pathogenesis;pathogenic fungus;Pathologic;Pathology;Pathway interactions;Patients;Pharmacotherapy;pre-clinical;prevent;Prevention;Quality of life;Reporting;response;Risk;Role;Specificity;standard care;standard of care;Survivors;Symptoms;synergism;T-Lymphocyte;targeted treatment;Therapeutic;Time;Tissues;treatment response;Validation;validation studies;Veterans;Virulence

PROJECT_TITLE: Offsetting CNS inflammatory damage with anti-CXCR3 antibody immunotherapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 INFB-K (01)]


ORG_CITY: MINNEAPOLIS

ORG_NAME: MINNEAPOLIS VA  MEDICAL CENTER

ORG_STATE: MN

PHR: Current therapies for prostate cancer aimed at targeting the androgen receptor (AR) fail due to development of drug-resistance. A possible mechanism is AR axis therapy stress-induced elevation of protein kinase CK2, a major player in cancer pathobiology and progression through its promotion of cell survival. The present work is to identify the mechanism of CK2 function in prostate cancer and to establish that using CX-4945/Silmitasertib (a clinical grade inhibitor of CK2) as a co-therapy may lead to improved precision management of prostate cancer patients.

PI_NAMEs: KLEIN, MARK A.;TREMBLEY, JANEEN H (contact)

PROJECT_TERMS: abiraterone;Address;advanced prostate cancer;Androgen Antagonists;androgen independent prostate cancer;Androgen Receptor;Androgens;Automobile Driving;Basic Science;Biological;Biopsy;Blood;Cancer Biology;cancer cell;cancer diagnosis;Cancer Patient;cancer survival;casein kinase II;Castration;Cell Survival;Cells;ChIP-seq;Chromatin;Clinical;Clinical Data;clinical translation;Clinical Trials;clinically relevant;cohort;CSNK2A1 gene;Data;data modeling;Data Set;deprivation;design;Development;Disease;Disease Progression;Disease Resistance;Disease-Free Survival;Drug Combinations;drug resistance development;Drug usage;efficacy evaluation;Enhancers;Ensure;enzalutamide;Evolution;extracellular;Fostering;genetic signature;Genetic Transcription;health definition;improved;Incidence;inhibitor;Investigation;Link;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;Messenger RNA;Military Personnel;Modeling;Nature;Neoplasm Metastasis;neoplastic cell;Non-Malignant;novel;Nuclear;Nuclear Protein;Oral;Outcome;patient stratification;Patient-Focused Outcomes;Patients;personalized management;Pharmaceutical Preparations;Phase;Phase Ib/II Clinical Trial;Phase II Clinical Trials;programs;Progression-Free Survivals;prospective;Prospective Studies;Prostate;prostate cancer cell;prostate cancer cell line;prostate cancer progression;Prostate Cancer therapy;Prostatectomy;Prostatic;protein complex;protein expression;Protein Kinase;Proteins;receptor binding;receptor expression;Receptor Signaling;Regulation;Research Proposals;Resistance;Resistance development;Retrospective Studies;Role;Sampling;Serum;Signal Transduction;Stress;Suggestion;Survival Rate;targeted treatment;therapy resistant;Time;Transcription Process;Transcriptional Regulation;transcriptome;transcriptome sequencing;Treatment Failure;treatment strategy;tumor;tumor progression;tumor xenograft;Validation;Veterans;Work

PROJECT_TITLE: Protein kinase CK2 in prostate cancer progression and clinical potential for therapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCA-S (01)]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: Project Narrative: Single nucleotide polymorphisms (SNPs) in the protein tyrosine phosphatase N2 (PTPN2) gene are confirmed risk markers in inflammatory bowel disease (IBD), and are associated with earlier onset and increased severity of disease. There are a lack of suitable model systems to study how PTPN2 variants compromise the function of intestinal epithelial cells, the critical cell type that comprises the gut barrier. In this proposal, we will utilize the unique resources of the IBDGC to develop cutting-edge models to uncover a greater translational understanding of how PTPN2 variants contribute to gut barrier dysfunction in IBD, and create novel tools for future ‘personalized’ drug development studies.

PI_NAMEs: MCCOLE, DECLAN  (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Address;Affect;American;Antibacterial Response;Bacteria;Bioinformatics;Biological;Biological Models;Biology;Caco-2 Cells;Celiac Disease;Cell Communication;Cell Line;cell type;chronic inflammatory disease;Clinical;Cluster Analysis;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Collaborations;Crohn's disease;Data Set;Development;Disease;drug development;early onset;Epithelial Cells;Epithelium;experimental study;Functional disorder;Future;Gene Cluster;Gene Expression;General Population;Genes;genetic analysis;genetic approach;genetic variant;Genotype;Goals;Health Care Costs;Human;Immune;in vitro Model;induced pluripotent stem cell;Inflammatory Bowel Diseases;inhibitor;insight;Insulin-Dependent Diabetes Mellitus;intestinal barrier;intestinal epithelium;intestinal homeostasis;Intestinal permeability;Intestines;knock-down;Knock-out;Knowledge;loss of function;lymphoblastoid cell line;Macrophage;Macrophage Activation;migration;Modeling;Modification;Molecular Target;novel;Organoids;Outcome;pathobiont;Pathogenesis;Pathway Analysis;Pathway interactions;Patients;Permeability;pharmacologic;Phosphorylation;Physiological;precision drugs;Proliferating;Property;Protein Analysis;protein expression;Protein Tyrosine Phosphatase;Resources;response;Risk;Risk Marker;risk variant;Role;Sampling;Severity of illness;Single Nucleotide Polymorphism;Source;stem cell organoids;System;tool;transcriptome sequencing;transcriptomics;Ulcerative Colitis;Variant;wound healing

PROJECT_TITLE: Targeted Identification of IBD Risk Gene Variant Impact on Immune-Epithelial Crosstalk and Intestinal Barrier Function

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-C (O1)]


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

ORG_CITY: SAINT LOUIS

ORG_DEPT: NEUROLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Alzheimer’s disease and related disorders represent a major public health problem with a great need for better treatments that can delay, slow, or prevent the disease. Based on recent data from our lab, we are determining the mechanisms via which T cells, antigen presenting cells, and microglia interact to lead to tau- mediated neurodegeneration. We are also exploring novel treatments based on targeting T cells and T cell signaling.

PI_NAMEs: HOLTZMAN, DAVID M. (contact);ULRICH, JASON D

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: abeta accumulation;adaptive immune response;Affect;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease related dementia;Alzheimer's disease risk;Amyloid beta-Protein;Amyloid deposition;Antigen-Presenting Cells;Antigens;Apolipoprotein E;apolipoprotein E-4;Area;Attenuated;Autoimmune Diseases;Brain;Brain Injuries;Brain region;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Count;Cells;cerebral atrophy;Characteristics;Clinical;Clonal Expansion;CTLA4-Ig;Data;Dementia;Dendritic Cells;Development;Disease;exhaust;functional decline;Histocompatibility Antigens Class II;HLA-DRB1;Human;Immune;Immunologics;Immunosuppressive Agents;Impaired cognition;Infiltration;Inflammatory;Innate Immune Response;insight;Interferon Type II;Knock-in;Knock-out;Libraries;Link;Major Histocompatibility Complex;medial temporal lobe;Mediating;MHC Class II Genes;Microglia;Mus;Neocortex;neocortical;Nerve Degeneration;neuron loss;Neurons;new therapeutic target;novel;Pathogenesis;Pathology;Pathway interactions;Peptide/MHC Complex;Peptides;perforin 1;Peripheral;Pharmaceutical Preparations;Play;prevent;programmed cell death protein 1;Protein Isoforms;Proteins;Public Health;receptor;Role;Signal Transduction;Stains;Surface;Synapses;T cell response;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;tau aggregation;tau Proteins;Tauopathies;TCR Activation;Testing;Time;Transgenic Mice;United States

PROJECT_TITLE: Role of T cells in tau-mediated neurodegeneration

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