ADMINISTERING_IC: HD

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

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

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: The research proposed in this application seeks to understand the neurodevelopmental mechanisms through which stable housing can reduce some of the negative effects of poverty on children. Childhood poverty is associated with lower academic achievement, under employment, and poorer health across the life course. This project examines the effect of stable housing on processes likely to improve these outcomes, including decision-making and impulse control.

PI_NAMEs: POLLAK, SETH D (contact);WOLFE, BARBARA L

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: 15 year old;Academic achievement;Academy;Address;Adolescence;Adolescent;Age;age group;Agreement;American;Area;Attention;Attenuated;Automobile Driving;Basic Science;Behavior;Behavior Control;Behavioral;Behavioral Mechanisms;behavioral outcome;biobehavior;Brain;brain control;Child;Child Care;Child Development;child poverty;child protective service;Childhood;Chronic;Chronic stress;cognitive control;cognitive process;Communities;Complex;Consent;County;COVID-19;Data;Decision Making;Development;early adolescence;early life adversity;effective intervention;effectiveness testing;efficacy evaluation;Employment;Environment;experience;Family;Functional Magnetic Resonance Imaging;Funding;Graduation Rates;Growth;Health;Health behavior;health economics;high risk;high school;Household;Housing;improved;improved outcome;Income;Individual Differences;Instruction;Intervention;Interview;Job loss;Judgment;Knowledge;Laboratories;Life;Life Cycle Stages;life span;Link;Literature;Long-Term Effects;Measures;Medical Assistance;neural;neural correlate;Neural Pathways;neurobehavioral;Neurobiology;Neurocognitive;Neurosciences;novel strategies;Nutritional;Outcome;Parents;Participant;Pathway interactions;Pediatrics;Performance;Policies;postnatal;Poverty;Problem behavior;Procedures;Process;programs;Public Health;Public Housing;Public Policy;Race;Randomized;Records;recruit;Research;Resources;Risk;Risk Behaviors;Risk Taking;Sampling;Schools;sex;Skin;socioeconomics;Specific qualifier value;Study Subject;Testing;Time;Treatment Efficacy;U.S. Department of Housing and Urban Development;unemployment insurance;uptake;voucher;Waiting Lists;Well in self;Wisconsin;Youth

PROJECT_TITLE: Child poverty, housing, and healthy decision-making

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: NEW ORLEANS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: LSU HEALTH SCIENCES CENTER

ORG_STATE: LA

PHR: We aim to define the molecular basis of HER3 signaling promotion of triple negative breast cancer (TNBC) progression and metastasis via upregulation of PHF8, a key histone lysine demethylase. The proposed studies will shed a new light on our understanding of epigenetic promotion of HER3-driven TNBC. Data generated will provide compelling evidence to develop novel therapeutic agents/strategies inhibiting HER3 or PHF8 either alone or in combination with chemotherapy for the patients with TNBC, especially those with the subtypes of Basal-like 1 (BL1), Luminal-Androgen receptor (LAR), or Basal-like 2 (BL2).

PI_NAMEs: LIU, BOLIN  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Androgen Receptor;anti-PD-1/PD-L1;anti-PD-L1 antibodies;Antibody-drug conjugates;Bioinformatics;Biology;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Patient;breast cancer progression;Cancer Cell Growth;cancer subtypes;Cell Line;Cell Proliferation;Cessation of life;chemotherapeutic agent;chemotherapy;Cisplatin;Clinical;Data;Data Set;Dimerization;Disease;Drug Combinations;Drug resistance;effective therapy;Epidermal Growth Factor Receptor;Epigenetic Process;ERBB2 gene;ERBB3 gene;Estrogen Receptors;Foundations;gain of function;Genetic Transcription;Goals;Heregulin;histone demethylase;Histones;Immunotherapy;In Vitro;in vivo;inhibitor;insight;Invaded;knock-down;Ligands;Light;loss of function;Lysine;Malignant Breast Neoplasm;Mediating;Mediator;Messenger RNA;Metastatic Neoplasm to the Lung;MicroRNAs;migration;Modeling;Molecular;molecular targeted therapies;Monoclonal Antibodies;Neoplasm Metastasis;neutralizing antibody;novel;novel therapeutics;Outcome;overexpression;Paclitaxel;Patient-derived xenograft models of breast cancer;Patients;PHD Finger;Play;Poly(ADP-ribose) Polymerase Inhibitor;Post-Transcriptional Regulation;Progesterone Receptors;Prognosis;Proteins;receptor expression;Receptor Protein-Tyrosine Kinases;Recurrent tumor;Relapse;research and development;Role;Sampling;Signal Pathway;Signal Transduction;Specimen;System;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic;Therapeutic Agents;therapeutically effective;transcriptome sequencing;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor progression;Up-Regulation

PROJECT_TITLE: HER3-PHF8 signaling axis in triple-negative breast cancer progression

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Dietary Supplements;Immunization;Immunotherapy;Nutrition;Prevention;Vaccine Related;Women's Health Research

ORG_CITY: HOUSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: Narrative-Relevance  This R01 application tackles one of the unmet challenging problems in the breast cancer field: prevention of estrogen receptor-negative (ER-) breast cancer. The major goal of this research is to determine whether and how vitamin E administration via both local and systemic deliveries would enforce dendritic cell antigen presentation, increase tumor antigen-specific T-cell response, boost effector memory T-cells, and potentiate cancer vaccine-induced immunoprevention against ER- mammary tumor and human breast cancer. If preclinical studies are successful, our new strategies could be fast-track translated into breast cancer immunoprevention clinical trials for women at high risk for ER- breast cancer.

PI_NAMEs: YU, DIHUA  (contact)

PROGRAM_OFFICER_NAME: PERLOFF, MARJORIE

PROJECT_TERMS: Agonist;Amaze;anti-cancer;anti-PD-1;Antigen Presentation;Antigen Presentation Pathway;Antigen-Presenting Cells;Antigens;Breast Cancer Patient;breast cancer vaccine;Breast Diseases;cancer diagnosis;Cancer Etiology;cancer prevention;cancer recurrence;Cancer Vaccines;CD34 gene;Cell Physiology;Cells;Cessation of life;Clinic;clinical investigation;Clinical Research;Country;Cytometry;Data;Dendritic cell activation;Dendritic Cell Vaccine;Dendritic Cells;dietary supplements;DNA Vaccines;ERBB2 gene;Estrogen receptor negative;Estrogen receptor positive;Future;Genetic Engineering;Genetically Engineered Mouse;Goals;High Risk Woman;Human;humanized mouse;Immune;Immune response;Immunity;immunogenic;Immunologic Surveillance;Immunophenotyping;Immunoprevention;immunoregulation;Immunotherapy;improved;Incidence;Injections;insight;Insulin-Like Growth-Factor-Binding Proteins;Malignant Breast Neoplasm;Malignant neoplasm of lung;Mammary Neoplasms;mortality;Mouse Mammary Tumor Virus;mouse model;Mus;Mutation;neoantigens;novel strategies;NR0B2 gene;Oral;patient response;Patients;PD-1/PD-L1;Peptide Vaccines;Peptides;Phase;Phase I/II Clinical Trial;Physiologic pulse;Pilot Projects;plasmid DNA;Play;preclinical study;prevent;Prevention;Prevention strategy;Prognosis;Raloxifene;Recurrence;Research;Role;Signal Transduction;Site;STING agonists;Survival Rate;T cell response;T memory cell;T-Lymphocyte Subsets;Tamoxifen;Testing;Toll-like receptors;Translating;treatment response;triple-negative invasive breast carcinoma;tumor;Tumor Antigens;Tumor Immunity;tumor initiation;tumor progression;tumor-immune system interactions;uptake;Vaccines;Vitamin E;Woman;women's clinical trial

PROJECT_TITLE: Exploring novel strategies for immunoprevention of estrogen receptor negative breast cancer

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

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

ORG_CITY: College Station

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

PHR: PROJECT NARRATIVE Women exposed to hexavalent chromium (Cr(VI)) suffer from pre-term labor, pre-mature abortion, and intrauterine fetal growth restriction (IUGR). In humans, exposure to endocrine-disrupting chemicals leads to inadequate uterine spiral artery remodeling in early pregnancy resulting in pregnancy-related disorders. The outcome of the proposed NIH-R21 project will lead to a better understanding of the molecular mechanism of Cr(VI) in causing maladaptation of placental /uterine vasculature, which leads to IUGR and pre-term labor, that in turn might help regulate Cr(VI) exposure in a vulnerable population, such as pregnant women.

PI_NAMEs: BANU, SAKHILA  (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: abortion;Actins;Adverse effects;Affect;Age;Apoptosis;Area;Arteries;Birth Rate;Blood;Blood Vessels;Carcinogens;Cells;Chemical Exposure;Child;Chromium Compounds;chromium hexavalent ion;Clinical Data;Collagen;Communities;Complex;contaminated water;Cytokeratin;Data;Databases;Diameter;Disease;Dose;early pregnancy;Elastin;Endocrine Disruptors;Endothelial Cells;Endothelium;Environmental Exposure;epidemiologic data;Euthanasia;experience;Experimental Designs;experimental group;Exposure to;Extracellular Matrix;Extracellular Matrix Proteins;Female;fetal;Fetal Development;Fetal Growth;Fetal Growth Retardation;Fetal Resorption;Fetal Weight;Fetus;Grant;Growth Factor;Health;Heavy Metals;High-Risk Pregnancy;Hospital Records;Human;human female;immunocytochemistry;indexing;Individual;Infant;Infertility;innovation;Interstitial Collagenase;Invaded;Label;Litter Size;male;Malignant Neoplasms;Mediating;Michigan;Modeling;Molecular;Newborn Infant;novel;Nutrient;Outcome;Oxidative Stress;Pathway interactions;Pattern;Perfusion;Persons;Placenta;Placentation;Potassium;Predisposition;Pregnancy;pregnancy disorder;pregnancy health;Pregnancy loss;Pregnancy Outcome;pregnant;Pregnant Women;premature;Premature Birth;Premature Labor;pressure;Proteins;PTK2 gene;pup;Rattus;Relaxation;Reporting;reproductive;response;Role;Shapes;Signal Pathway;Signaling Molecule;Site;spatiotemporal;Spiral Artery of the Endometrium;Spontaneous abortion;STAT1 gene;STAT3 gene;Stat5 protein;Thick;Time;trophoblast;United States;United States National Institutes of Health;Uterus;Vascular remodeling;Vascular Smooth Muscle;Vulnerable Populations;water quality;Woman;working group

PROJECT_TITLE: Evaluating the effects of hexavalent chromium on uterine vascular remodeling

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Liver Disease;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: DETROIT

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: The cytoplasmic sulfotransferase (SULT) conjugating enzymes are expressed from the earliest stages of human development and throughout the life-course. The SULTs metabolize both endogenous and foreign chemicals, sometimes to less toxic or inactive compounds and sometimes to reactive and carcinogenic compounds, and so are important determinants of the effects of the environment on the human during critical early windows of susceptibility that can program an individual’s likelihood of developing disease later in life. SULT expression varies markedly among individuals and changes over time, but the mechanisms that control these dynamic changes in metabolic capability are not understood. This project will undertake the challenge of developing a comprehensive and detailed understanding of the mechanisms that control SULT expression and function during human development.

PI_NAMEs: RUNGE-MORRIS, MELISSA A (contact)

PROJECT_TERMS: Address;Adult;Affect;Binding;Biological Assay;Birth;carcinogenicity;Carcinogens;Cells;Chemicals;Chromatin;chromatin immunoprecipitation;cofactor;Cytoplasm;Data;Development;Developmental Process;Disease;Environment;Environmental Exposure;Environmental Pollutants;Enzymatic Biochemistry;Enzymes;Estrogens;Estrone sulfotransferase;fetal;Fetal Liver;Fetus;Food;Genes;Genetic Transcription;genome-wide;Hepatic;Hepatocyte;High-Throughput Nucleotide Sequencing;Hormones;Human;Human Activities;Human Development;human model;In Situ;Individual;induced pluripotent stem cell;insight;Investigation;Kinetics;knock-down;Knowledge;Life;Life Cycle Stages;Liver;liver development;Metabolic;Metabolism;Modeling;Molecular;molecular modeling;monoamine-sulfating phenol sulfotransferase;Neurotransmitters;Nucleic Acid Regulatory Sequences;Pattern;Pharmaceutical Preparations;pharmacophore;Physiological;Placenta;Predisposition;Pregnancy;prenatal;Probability;Prodrugs;programs;Property;Qualifying;Regulation;Reporter;Research;Role;small hairpin RNA;Specimen;stem cell model;Sterols;Structure;Substrate Specificity;sulfotransferase;Testing;Time;Toxic effect;transcription factor;Transposase;vector;Xenobiotics

PROJECT_TITLE: Expression, Regulation and Function of the SULT1C Carcinogen-Activating Enzymes

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Genetic Testing;Genetics;Mental Health;Pediatric;Prevention;Social Determinants of Health;Telehealth;Women's Health Research

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Young adult women biologically-related to people carrying breast cancer-causing genes may be at high risk for developing breast cancer themselves. These relatives should take precautions to learn about their risk and possibly act on it. Our study aims to understand how trained peer coaches can help young adult women navigate this process--potentially changing how they learn to control hereditary breast cancer.

PI_NAMEs: O'NEILL, SUZANNE C. (contact);TERCYAK, KENNETH

PROGRAM_OFFICER_NAME: FERRER, REBECCA

PROJECT_TERMS: Address;Adult women;Affective;Age;behavioral outcome;brca gene;BRCA mutations;Breast Cancer Risk Factor;Breast Magnetic Resonance Imaging;Cancer Burden;cancer care;Cancer Center;Cancer Control;cancer genetics;cancer prevention;cancer risk;Cancer Survivor;career;Caring;Clinical;Clinical Trials;clinically significant;Communities;Conflict (Psychology);coping;Coping Skills;Counseling;Data;Decision Making;Development;Diagnosis;Disadvantaged;Distress;Emotional;empowerment;Engineering;Equation;evidence base;expectation;experience;Face;Family;Family Planning;feasibility trial;Funding;Genes;Genetic;Genetic Counseling;Genetic Predisposition to Disease;genetic testing;Genomic medicine;Health;Health Personnel;Hereditary Breast and Ovarian Cancer Syndrome;Hereditary Breast Carcinoma;high risk;High-Risk Cancer;improved;improved outcome;indexing;innovation;interest;Intervention;intervention effect;Learning;Life Cycle Stages;Literature;Magnetic Resonance Imaging;Malignant Breast Neoplasm;Malignant Neoplasms;Mammography;Manuals;Mediating;Medical;meetings;Memorial Sloan-Kettering Cancer Center;Modeling;mutation carrier;Operative Surgical Procedures;Outcome;Participant;Partner in relationship;Pattern;peer;peer coaching;peer support;Persons;Population;population health;premature;Printing;Problem Solving;Process;programs;Protocols documentation;psychologic;psychological distress;psychosocial;psychosocial outcome;Quality of life;Randomized;Recommendation;recruit;Reporting;response;Risk;Risk Estimate;Risk Management;Risk Reduction;screening;Second Degree Relative;Self Efficacy;Services;Site;skills;Social support;stress reduction;Surveys;Target Populations;Telephone;telephone coaching;Testing;theories;Training;treatment as usual;trial enrollment;ultrasound;Uncertainty;United States National Academy of Sciences;uptake;Woman;Work;young adult

PROJECT_TITLE: Peer Support for Young Adult Women with High Breast Cancer Risk

STUDY_SECTION: PRDP

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


NIH_SPENDING_CATS: Cancer;Genetics;Lung;Lung Cancer

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

PHR: Project Narrative  Lung cancer is the leading cause of cancer deaths among men and women in the United States. Using laboratory-based science, this project aims to elucidate novel functions and the regulation of an enzyme, MOF/KAT8, in lung cancer. This research has the potential to save lives and improve lung health by advancinge strategies for lung cancer treatment.

PI_NAMEs: SETO, EDWARD  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, RONALD L

PROJECT_TERMS: Acetylation;Acetyltransferase;Adenocarcinoma Cell;Affect;Binding;cancer diagnosis;Cancer Etiology;Cancer Prognosis;cancer therapy;Cell Physiology;Cessation of life;Complex;Cytokine Gene;Data;Data Set;Deacetylase;Deacetylation;Development;Disease;DNA Damage;Embryonic Development;Enzymes;epithelial to mesenchymal transition;Epithelium;Event;Family;Future;Gene Expression;Gene Expression Regulation;gene repression;Genes;Genetic Transcription;HDAC2 gene;Histone Deacetylation;Histone H4;Histones;Immunohistochemistry;improved;insight;interest;Knock-in Mouse;Knock-out;knowledge of results;KRAS2 gene;Laboratories;Link;loss of function;Lung;Lung Adenocarcinoma;lung health;lung tumorigenesis;Lysine;MADH4 gene;male;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;member;men;Methyltransferase;Molecular;mouse model;non-histone protein;novel;novel therapeutic intervention;Outcome;Patient-Focused Outcomes;Patients;Play;Post-Translational Protein Processing;Process;promoter;protein function;Proteins;Regulation;Repressor Proteins;Research;response;Role;Science;Signal Transduction;SIRT1 gene;Site;survival outcome;Testing;The Cancer Genome Atlas;Therapeutic;therapeutic target;Tissues;TP53 gene;Transcription Repressor;transcriptome sequencing;Transforming Growth Factor beta;treatment strategy;tumor;Ubiquitination;United States;Woman;Work

PROJECT_TITLE: Targeting lysine acetyltransferase MOF/KAT8 in lung cancer

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Mental Health;Neurosciences

ORG_CITY: MINNEAPOLIS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative Fundamental behaviors, including reward-based learning, attention, and movement invigoration, rely on a complex recurrent network of striatal, midbrain, thalamic, and cortical brain circuit loops. Here, we propose to functionally dissect the anatomical organization of this system, using new methods to simultaneously manipulate and measure neural activity in multiple circuits at once during behavior. Our goal is to better understand information flow at the network level, for insight into basic neurobiological mechanisms of normal and pathological states.

PI_NAMEs: SAUNDERS, BENJAMIN THOMAS (contact)

PROGRAM_OFFICER_NAME: FERNANDEZ, FERNANDO R

PROJECT_TERMS: Anatomy;Animals;Architecture;Association Learning;Attention;Automobile Driving;Back;Behavior;Behavioral;Biosensor;body position;Brain;Cells;Cognition;Communication;Complex;Consumption;Corpus striatum structure;Cues;Data;Development;Disease;Disinhibition;Dopamine;Dopaminergic Cell;dopaminergic neuron;Dorsal;Fiber;gamma-Aminobutyric Acid;Glutamates;Goals;Head;in vivo;Influentials;innovation;insight;Learning;learning engagement;Measures;Methods;Midbrain structure;Modeling;Monitor;Motivation;Motor Cortex;Movement;neural;neurobiological mechanism;Neurobiology;Neurons;Nucleus Accumbens;optogenetics;Output;Pathologic;Pathway interactions;Pattern;Photometry;Positioning Attribute;Process;Rat Transgene;Rattus;recruit;Recruitment Activity;Recurrence;Rewards;Role;sensor;Series;Signal Transduction;Site;Stimulus;Substantia nigra structure;Sucrose;Synapses;System;Testing;Thalamic structure;Time;Training;Transgenic Organisms;transmission process;Ventral Striatum;Ventral Tegmental Area

PROJECT_TITLE: Functional architecture of striatal networks in cue-reward learning

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: NARRATIVE Maintaining normal calcium and phosphate homeostasis is essential for a myriad of cellular and metabolic functions that promote healthy skeletal development and ensure optimal organ function. Disordered mineral homeostasis causes metabolic bone diseases and nephrolithiasis, and is a common and morbid complication of chronic kidney disease. By performing the first detailed analyses of the tissue-specific effects of the vitamin D degrading enzyme, CYP24A1, in health and in disease, we will generate new evidence to support the design of novel therapies to enhance treatment of metabolic bone diseases, nephrolithiasis and chronic kidney disease.

PI_NAMEs: WOLF, MYLES S (contact)

PROGRAM_OFFICER_NAME: CHAN, KEVIN E

PROJECT_TERMS: Address;Adenine;Animals;Attention;Attenuated;Biological Assay;Blood Vessels;bone;Bone Diseases;Calcium;calcium absorption;Cardiac;Cardiovascular Diseases;Catabolism;Cessation of life;Chronic Kidney Failure;Complication;CRISPR/Cas technology;CYP27B1 gene;Data;design;Diet;Dihydroxycholecalciferols;Disease;Ensure;Enterocytes;Enzymes;fibroblast growth factor 23;Fibroblast Growth Factor Receptors;Fracture;Genes;Genetic;genetic approach;genome wide association study;Health;Heart;Histology;Homeostasis;Human;Human Genome;Hypercalcemia;in vivo;indexing;inhibitor;inorganic phosphate;Intestines;Intoxication;Investigation;Kidney;Kidney Diseases;Knockout Mice;Liver;Longitudinal Studies;loss of function mutation;Measures;Metabolic;Metabolic Bone Diseases;Minerals;Mixed Function Oxygenases;Molecular;mouse model;Mus;Nephrolithiasis;nephrotoxicity;novel;novel therapeutic intervention;novel therapeutics;Organ;Organoids;Phenotype;Physiological;Protein Isoforms;PTH gene;Regulation;Renal function;Research;Role;Secondary Hyperparathyroidism;Serum;Signal Pathway;Signal Transduction;Skeletal Development;Structure;Surgical Models;Syndrome;synthetic enzyme;Tamoxifen;Testing;Tissues;Toxic effect;Variant;Vitamin D;Vitamin D3 Receptor;Wild Type Mouse

PROJECT_TITLE: Tissue-Specific Regulation and Effects of CYP24A1

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Lung;Pulmonary Fibrosis;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative Idiopathic pulmonary fibrosis (IPF) is a disease that is more prevalent in the elderly, but it is not clear how cell types that contribute to aging can promote lung fibrosis. Our proposal will take advantage of a novel tool to identify and characterize senescent cells, a cell type that accumulates with aging, in lung fibrosis. Our study will define how senescent cells promote lung fibrosis, and screen for drugs that might better target these cells.

PI_NAMEs: PENG, TIEN  (contact)

PROGRAM_OFFICER_NAME: LIN, SARA

PROJECT_TERMS: 3-Dimensional;Address;Adoptive Cell Transfers;Adoptive Transfer;age acceleration;age related;Age related pathologies;age-related disease;aged;Aging;Alveolus;Area;Biological Assay;Biological Markers;Biology;CDKN2A gene;cell behavior;Cell Cycle Arrest;Cell Line;Cell Separation;cell type;Cells;Characteristics;Chemicals;Chronic lung disease;Cicatrix;Collagen;combinatorial;Cues;Data;defined contribution;Disease;disease model;Drug Screening;Elderly;Engineering;epithelial stem cell;Epithelium;Exhibits;Fibroblasts;Fibrosis;fibrotic lung;fibrotic lung disease;functional decline;Genetic;genetic approach;Genetic Models;high throughput screening;Human;idiopathic pulmonary fibrosis;Image;In Vitro;in vivo;Induction of Apoptosis;Inflammatory;Injury;Knowledge;Ligands;Lung;lung injury;Maintenance;Metaplasia;Methodology;migration;Modeling;Morphology;Mus;novel;Organ;Organoids;Outcome;Pathogenesis;Pathologic;Phenotype;Physiological;Process;progenitor;programs;prospective;Pulmonary Fibrosis;rational design;regenerative cell;Regenerative response;Reporter;Reporting;response;Risk Factors;Role;screening;senescence;senescent cell;senolytics;single cell analysis;single-cell RNA sequencing;stem cell division;stem cell expansion;stem cells;Testing;Therapeutic;therapeutic target;Time;Tissues;tool;Traction;Transplantation;Tumor Suppressor Proteins;tumorigenesis;Uncertainty;Validation;wound healing

PROJECT_TITLE: Deciphering the role of p16INK4A+ fibroblasts in lung fibrosis

STUDY_SECTION: LIRR

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


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Eye Disease and Disorders of Vision;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: BALTIMORE

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative  Retinal vein occlusion is a leading cause of vision loss for which present therapy is limited to incompletely treating the complications of the occluded vein, rather than by directly addressing the causative thrombus. Retinal vein cannulation with precise delivery of therapeutic agent is a very difficult freehand procedure that is well suited to robotic assistance—and potentially best suited for bilateral robotic support. To consistently enable human clearance of obstruction in a retinal vein, we propose to develop a novel bilateral robotic system that will enhance retinal vein cannulation efficiency, success and safety via coordinated bilateral robotic assistance with real-time, multipoint, multisensory feedback.

PI_NAMEs: GEHLBACH, PETER LOUIS;IORDACHITA, IULIAN IOAN (contact);KOBILAROV, MARIN

PROGRAM_OFFICER_NAME: BITTMANN, MORIA FISHER

PROJECT_TERMS: adaptive learning;Address;Affect;Algorithms;Animal Model;Apoptosis;Area;Behavior;Bilateral;Blindness;Blood coagulation;Blood Vessels;Cannulas;Cannulations;Clinical;Clinical Treatment;Coagulation Process;Cognitive;Discipline;Disease;Emerging Technologies;experience;Eye;Eye diseases;Eye Movements;Family suidae;Fatigue;Goals;Grant;Hand;Hemorrhage;Human;Hybrids;in vivo;in vivo Model;Infusion procedures;Injury;innovation;instrument;Ischemia;machine learning method;Manuals;Maps;Measures;Micromanipulation;Microsurgery;Motion;multisensory;Needles;Neural Retina;Neurons;neurosurgery;novel;Obstruction;Operative Surgical Procedures;Otolaryngology;Perception;Performance;Perfusion;Persons;Pharmaceutical Preparations;Physiological;Positioning Attribute;pre-clinical;prevent;Procedures;Psyche structure;Puncture procedure;Readiness;real time monitoring;Reproducibility;Research;Retina;retina blood vessel structure;Retinal Diseases;retinal regeneration;Retinal Vein Occlusion;Robot;robot assistance;robot control;robotic system;Robotics;Safety;Sclera;Sensory;sensory feedback;Sensory Thresholds;Stress;Structure of central vein of the retina;success;Surgeon;System;Tactile;Techniques;Technology;theories;Therapeutic Agents;Thrombus;Time;Tissues;tool;Translations;Tremor;Validation;vein occlusion;Veins;virtual;Vision;Visualization;Work

PROJECT_TITLE: Enabling Technology for Safe Robot-assisted Surgical Micromanipulation

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Genetics;Immunotherapy;Pancreatic Cancer;Rare Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Tumor intrinsic CREB activation exacerbates the immunosuppressive tumor microenvironment and hinders the adaptive immune response in pancreatic cancer. Targeting CREB can remodel the tumor immune microenvironment, specifically through macrophage signaling, to enhance the efficacy of immunotherapy. This study will investigate the tumor intrinsic cellular mechanism of CREB-mediated immunosuppression using various preclinical mouse models and clinical samples to refine ongoing therapeutic approaches to this lethal disease.

PI_NAMEs: NAGATHIHALLI, NAGARAJ S. (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: adaptive immune response;Affect;anti-tumor immune response;attenuation;Automobile Driving;Binding;Biological Response Modifiers;CD8-Positive T-Lymphocytes;cell growth;Cell Line;Cells;checkpoint inhibition;checkpoint therapy;Chemotaxis;chemotherapeutic agent;Clinical;clinically relevant;Complement;Complex;CRISPR/Cas technology;Cyclic AMP-Responsive DNA-Binding Protein;cytokine;Data;Development;Disease;effective therapy;Fibrosis;gene regulatory network;Genetic;Genetic Models;Genetic Transcription;Genetically Engineered Mouse;genome editing;High-Throughput Nucleotide Sequencing;Human;humanized mouse;Immune;Immune checkpoint inhibitor;immunomodulatory therapies;Immunophenotyping;immunoregulation;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Impairment;improved;in vivo;Infiltration;Inflammation;inhibitor;insight;Interleukin-6;Knock-out;KRAS2 gene;Laboratories;leukemia inhibitory factor receptor;LIF gene;Macrophage;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;Modeling;Molecular;mortality;mouse model;Mus;Myelogenous;Myeloid-derived suppressor cells;Nature;Neoplasm Metastasis;Neoplasms;neoplastic cell;novel therapeutic intervention;Oncogenic;Organoids;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;pancreatic neoplasm;paracrine;Pathway interactions;patient derived xenograft model;Patients;pharmacologic;Phenotype;pre-clinical;preclinical study;Primary Neoplasm;Production;Prognosis;promoter;Receptor Signaling;recruit;Regulation;Regulatory T-Lymphocyte;release factor;Resistance;response;Role;Safety;Sampling;Shapes;Signal Transduction;STAT3 gene;synergism;T-Cell Activation;T-Lymphocyte;Therapeutic;therapy resistant;Time;Tissues;transcription factor;transcription regulatory network;treatment strategy;tumor;Tumor Burden;tumor growth;tumor microenvironment;Tumor Promotion;Tumor-associated macrophages;tumor-immune system interactions;tumorigenesis;Up-Regulation;Work

PROJECT_TITLE: Impact of CREB-driven mechanism in shaping the tumor-immune landscape

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-D(08)F]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Brain Disorders;Neurosciences

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative G protein–coupled receptors, the targets of one-third of all FDA-approved drugs, undergo a set of concerted conformational changes that enable them to respond to external stimuli and stimulate intracellular signaling. This proposal proposes to develop a computational–experimental biophysical approach to determine the activation mechanisms for members of a GPCR subfamily, the metabotropic glutamate receptors, thereby enabling discovery of new ligands with safer therapeutic profiles.

PI_NAMEs: LATORRACA, NAOMI  (contact)

PROGRAM_OFFICER_NAME: HARTON, MARIE DEBORAHGAYNELLE

PROJECT_TERMS: academic preparation;addiction;Address;Adopted;Affect;Affinity;Binding;Biochemical;biophysical techniques;Biophysics;career;Cell membrane;Clinic;Communication;Complex;computer studies;cost;Data;design;Deuterium;Development;dimer;Disease;Doctor of Philosophy;drug discovery;Drug Targeting;Elements;Environment;experimental study;extracellular;Extracellular Domain;Family;FDA approved;flexibility;Fluorescence Resonance Energy Transfer;G-Protein-Coupled Receptors;glutamatergic signaling;Glutamates;Goals;Hydrogen;Hydrogen Bonding;Individual;Investigation;Knowledge;Learning;Leucine-Rich Repeat;leucine-rich repeat protein;Ligand Binding;Ligand Binding Domain;Ligands;Maps;Mass Spectrum Analysis;Measurement;member;Membrane Proteins;Mental Depression;Mental disorders;Mentors;Metabotropic Glutamate Receptors;Molecular Conformation;molecular dynamics;Monitor;Motion;Nature;Nervous System Disorder;novel;novel strategies;Output;Pathway interactions;Pharmaceutical Preparations;Physics;Point Mutation;Population;Positioning Attribute;post-doctoral training;Postdoctoral Fellow;programs;Protein Conformation;Protein Family;Proteins;rational design;receptor;Receptor Activation;Regulation;Reporting;Research;response;Schizophrenia;side effect;Signal Transduction;Signaling Protein;simulation;single molecule;skills;Specificity;Stimulus;structural biology;structural determinants;Supervision;Surface;Synapses;System;temporal measurement;Tertiary Protein Structure;Testing;theories;Therapeutic;therapeutic target;Training;Transmembrane Domain;transmission process;Variant;Work

PROJECT_TITLE: Decoding Structural Determinants of Efficacy and Specificity in a GPCR Subfamily


ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative Humans have an incredible number of different T Cell Receptors (TCR) giving T cells their specificity; some of these, called "public TCRs," are shared in the population and may have important functions. We have discovered 3 special public TCRs whose presence in the peripheral blood of cancer patients correlates with progression free and overall survival. In this proposal, we will investigate the scope of predictive power for these special public TCRs and investigate their potential for therapeutic applications.

PI_NAMEs: POLLACK, SETH M (contact)

PROGRAM_OFFICER_NAME: SORG, BRIAN S

PROJECT_TERMS: Adult;alpha-beta T-Cell Receptor;Amino Acid Sequence;Antigens;Autoantigens;Autoimmune Diseases;Autoimmunity;Awareness;Biological Markers;blood-based biomarker;cancer immunotherapy;cancer infiltrating T cells;Cancer Patient;CD4 Positive T Lymphocytes;CD8B1 gene;Cell Separation;Cells;Clinical;Clone Cells;cohort;complementarity-determining region 3;CTAG1 gene;Cytomegalovirus;Data;Gene Rearrangement;HIV;Human;Human Herpesvirus 4;Immune checkpoint inhibitor;Immunophenotyping;Immunotherapy;immunotherapy trials;improved;Individual;Institution;J-Chain Immunoglobulins;Life;Link;Malignant neoplasm of lung;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Melanoma Cell;Melanoma patient;Merkel cell carcinoma;neoantigens;novel;Nucleotides;Outcome;outcome prediction;pathogenic virus;Patient-Focused Outcomes;Patients;PDL1 inhibitors;Peptides;peripheral blood;Peripheral Blood Mononuclear Cell;Persons;Phenotype;Play;polypeptide;Population;Predictive Value;Process;prognostic value;Progression-Free Survivals;Proteins;Renal Cell Carcinoma;Risk Reduction;Sarcoma;Specificity;T cell receptor repertoire sequencing;T-Cell Development;T-Cell Receptor;T-Lymphocyte;Testing;Therapeutic;Thymus Gland;transcriptome sequencing;tumor;Viral

PROJECT_TITLE: Special Public T Cell Receptor Sequences that Predict Outcomes for Cancer Patients


ORG_CITY: DAVIS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative All cells in tissues and organs experience some degree of physical forces, but how cells react to such forces is not well defined. Using innovative techniques to detect protein associations, we will determine how physical forces change protein interactions surrounding cyto-keratins, a family of fibrous proteins required for maintaining the physical integrity of cells and tissues. This proposal aims to understand the molecular basis of the keratin network’s force-induced responses and reveal novel keratin functions that may contribute to how cancer cells break free from their primary tissues and metastasize to tissues elsewhere and identify targets for novel therapeutics.

PI_NAMEs: YAMADA, SOICHIRO  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: 3-Dimensional;Actins;Adhesions;Animal Model;Behavior;Binding;Biochemical;Biological;biophysical techniques;Biotin;cancer cell;candidate identification;cell behavior;cell motility;Cell Physiology;Cells;Cytokeratin;Cytokeratin filaments;Cytoskeleton;Data;Dependence;Disease;Elements;Environment;Epithelial Cells;Epithelium;experience;Extracellular Matrix;Family;Fiber;fibrous protein;Gene Expression;Gene Expression Profile;Genetic Transcription;Goals;In Situ;In Vitro;in vivo;innovation;Intermediate Filament Proteins;Keratin;Knowledge;Label;Link;Maintenance;Malignant Neoplasms;mechanical properties;mechanotransduction;Mediating;Molecular;Needles;Neoplasm Metastasis;new therapeutic target;novel;Organ;Physical Stimulation;Physiological;Property;protein protein interaction;protein purification;Proteins;Proteomics;Reaction;Recombinant Proteins;reconstitution;recruit;Regulation;response;Role;Sagittaria;Signal Pathway;Signal Transduction;Stretching;Techniques;Testing;Time;Tissues;Transcriptional Regulation;Tumor Promoters;Tumor Suppressor Proteins

PROJECT_TITLE: Molecular basis of force-sensing by the keratin network

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-H(80)S]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Health Services;Mental Health;Mental Illness;Pediatric;Social Determinants of Health

ORG_CITY: SANTA MONICA

ORG_NAME: RAND CORPORATION

PHR: Project Narrative This project will examine how large-scale increases in funding for and access to school counselors, through California’s 2006 Supplemental School Counseling Program, impacted youth mental health, health behaviors, and well-being. It will describe how schools used the funding to increase access to counselors and mental health services, and examine heterogeneity in policy implementation and impacts by gender, race, geography, and income, which is important given disparities in access to mental healthcare and the incidence of mental health disorders. This study will have a high impact because it can inform the current policy debate about whether and how to expand mental health counseling in schools, and it will provide evidence on how to effectively design related policies so that they impact the children most in need of these services and address the current national child and adolescent mental health emergency.

PI_NAMEs: MULHERN, CHRISTINE  (contact)

PROGRAM_OFFICER_NAME: MARRO, MARY ACRI

PROJECT_TERMS: Academic achievement;Academy;access disparities;Address;adolescent health;adolescent mental health;Adolescent Psychiatry;Adult;Adverse event;Advocate;Age;aged;American;Anxiety;Attention deficit hyperactivity disorder;Behavior;Black race;California;Certification;Child;Child Health;Child Mental Health;Child Psychiatry;Counseling;Country;COVID-19;Data;demographics;design;Diagnosis;Disease;Education;Emergency department visit;Emergency Situation;Ethnic Origin;Event;experience;falls;Family;Funding;Future;Gender;Geography;Goals;Grant;Health;Health behavior;Health behavior and outcomes;health care availability;Health Professional;Health Services Accessibility;Heterogeneity;high risk;high school;Hispanic;Hour;Human Resources;improved;Incidence;Income;insight;instrument;Intervention;junior high school;Licensing;Life;Light;Low income;Measures;Medical;Mental Depression;Mental disorders;Mental Health;mental health counseling;Mental Health Services;Modeling;National Institute of Child Health and Human Development;Observational Study;Outcome;pandemic disease;Parents;Patient Self-Report;Pediatric Hospitals;Pediatrics;peer;Performance;Personal Satisfaction;Persons;Policies;Policy Maker;poor health outcome;Professional counselor;programs;Provider;Race;Records;Research;Research Design;Schools;Services;Students;Study models;suicidal risk;Suicide attempt;suicide rate;Surveys;Time;transition to adulthood;Urbanicity;Variant;Youth

PROJECT_TITLE: School Counselors and Children's Mental Health

STUDY_SECTION: SSPB

STUDY_SECTION_NAME: Social Sciences and Population Studies B Study Section[SSPB]


NIH_SPENDING_CATS: Genetics

PHR: PROJECT NARRATIVE Gene expression requires the splicing of mRNA precursors by the spliceosome, a dynamic cellular ribonucleoprotein machine of staggering complexity harboring over 150 proteins in human cells and mutated in numerous cancers. We recently developed the first global genetic methods for investigating the function of the spliceosome in haploid human cells. In this project, we will leverage our new methods and reagents to explore functions of individual spliceosomal proteins to understand human-specific features of gene expression in a manner not possible previously.

PI_NAMEs: MADHANI, HITEN D (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: 3' Splice Site;Alleles;Amino Acids;base editing;Binding;Biological Assay;C-terminal;Cell Line;Cells;Chicago;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Conserved Sequence;cost;CRISPR/Cas technology;Cytosine;Decision Making;design;experimental study;Family;flexibility;forward genetics;Gene Expression;Genes;Genetic;genetic approach;Genetic study;Goals;Hand;Haploid Cells;Haploidy;helicase;Homologous Gene;Human;improved;In Vitro;in vivo;Individual;inhibitor;Introns;Label;Lead;Length;Malignant Neoplasms;member;Methods;Missense Mutation;Molecular;molecular phenotype;mRNA Precursor;Mutagens;mutant;Mutate;Mutation;mutation screening;Phenotype;Point Mutation;predictive modeling;preference;programs;Proline;Protein Isoforms;Proteins;Reagent;Regulation;Reporter;Reporter Genes;Resistance;resistance mutation;Ribonucleoproteins;RNA Splicing;RNA-Binding Proteins;Role;Saccharomyces cerevisiae;Signal Transduction;Site;Spliceosomes;System;Testing;transcriptome sequencing;U1A protein;U2 Small Nuclear Ribonucleoprotein;Validation;Variant;Work;Yeasts

PROJECT_TITLE: Mechanisms of Gene Expression

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


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);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences

PHR: Narrative Cells are equipped with enzymes to generate physiological amyloids. These enzymes govern amyloidogenesis by regulating unusually long poly(A)-rich RNA tails that act as linear polyanionic stimulants of amyloid fiber formation. These enzymes modulate amyloid toxicity in Alzheimer’s and Parkinson’s disease models.

PI_NAMEs: BOKROS, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: active control;age related;Aging;alpha synuclein;Alzheimer's Disease;Amyloid;Amyloid beta-Protein;Amyloid deposition;Amyloid fibers;Amyloid Fibrils;amyloid formation;amyloidogenesis;beta pleated sheet;Biological Process;Biology;cell assembly;Cells;cofactor;combat;Complement;Data;Dedications;Disease;disease model;Enzymes;Equilibrium;exhaust;exosome;Family;genetic manipulation;innovation;Link;Liquid substance;Modeling;novel strategies;nucleotidyltransferase;Organism;Parkinson Disease;Pathologic;Phase;Phase Transition;Physical condensation;Physiological;Poly(A)+ RNA;Process;programs;Property;protein aggregation;protein folding;proteotoxicity;Regulation;Research;Ribosomal RNA;RNA;RNA Degradation;RNA Folding;Solid;Stimulant;Tail;Testing;Toxic effect

PROJECT_TITLE: Uncovering an Enzymatic Program that Drives Physiological and Pathological Amyloid Formation.

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development Facilitating The Transition to Independence Study Section[AGCD-1]


ORG_NAME: LIEBER INSTITUTE, INC.

PHR: Project Narrative Cognitive impairment is a core feature of many psychiatric and neurological disorders and a major unmet therapeutic need. This project will provide novel compounds to study the role of the dopamine D5 receptor in neurobiology, behavior, and ultimately its utility as a therapeutic target.

PI_NAMEs: BARROW, JAMES ;CARR, GREGORY V (contact)

PROGRAM_OFFICER_NAME: MANDELBLAT-CERF, YAEL

PROJECT_TERMS: Adverse effects;Agonist;Behavior;Binding;Binding Sites;Biological Assay;Brain;Brain-Derived Neurotrophic Factor;candidate identification;Cell Line;Cells;Characteristics;Chemicals;Clinical Research;Cognitive;cognitive function;counterscreen;Cyclic AMP;design;Dopamine;Dopamine D1 Receptor;dopamine D5 receptor;Drug Kinetics;experimental study;Exposure to;Family;Feedback;functional outcomes;G-Protein-Coupled Receptors;Goals;high throughput screening;Human;Impaired cognition;improved;In Vitro;in vitro activity;in vivo;in vivo evaluation;Ion Channel;Knock-in Mouse;Ligands;Measures;Mediating;Mental disorders;Metabolic;mouse model;Mus;Nervous System Disorder;Neurobiology;Neurons;Neurophysiology - biologic function;neuropsychiatric disorder;new therapeutic target;novel;novel therapeutic intervention;Patient-Focused Outcomes;Penetration;Pharmacodynamics;Physiology;Plasma;Play;positive allosteric modulator;Prefrontal Cortex;Property;receptor;Receptor Signaling;Research;Role;screening;Second Messenger Systems;Signal Pathway;Signal Transduction;Site;small molecule;Testing;Therapeutic;therapeutic target;tool;Validation

PROJECT_TITLE: Small-molecule probes for augmenting D5 receptor signaling

STUDY_SECTION: DDNS

STUDY_SECTION_NAME: Drug Discovery for the Nervous System Study Section[DDNS]


NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Hematology;Orphan Drug;Patient Safety;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Currently, diagnosis of graft vs host disease (GVHD) is often complicated by the potential of chemotherapy/infectious colitis in patients that have undergone allogeneic hematopoietic stem cell transplant.This proposal seeks to evaluate Multispectral optoacoustic tomography (MSOT) imaging as a method to separately detect and stratify patients with GVHD from patients with chemotherapy/infectious colitis.

PI_NAMEs: HOLTER CHAKRABARTY, JENNIFER LIN (contact);MCNALLY, LACEY R

PROGRAM_OFFICER_NAME: BEIER, HOPE THOMAS

PROJECT_TERMS: Abdomen;Adverse event;Alloantigen;Allogenic;Anesthesia procedures;Autoimmune Responses;Biological Markers;Biopsy;Body Weight decreased;Caring;Categories;chemotherapy;Clinical;clinical diagnosis;clinical efficacy;Clinical Research;Clinical Trials;Colitis;Collagen;Colonoscopy;Complication;congenital immunodeficiency;Contrast Media;Crohn's disease;Data;deoxyhemoglobin;Deposition;Diagnosis;diagnostic accuracy;Diagnostic tests;Disease;Dose;Endoscopy;experience;Feces;gastrointestinal;Genetic Diseases;Goals;graft vs host disease;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;Hemoglobin;high risk;histological stains;Human;Image;Immune system;Immunocompromised Host;immunodeficiency;Immunologic Deficiency Syndromes;improved;individual patient;Infectious colitis;Intervention;Intestines;Liver;Methods;Modality;Molecular;mortality;Mus;Muscular Dystrophies;Non-Neoplastic Hematologic and Lymphocytic Disorder;optoacoustic tomography;Output;Oxyhemoglobin;Pathologic;Patient risk;patient stratification;Patients;personalized medicine;Pharmaceutical Preparations;Phase;photoacoustic imaging;Physicians;Pilot Projects;Refractory;Risk;safe patient;safety assessment;safety testing;Schedule;Skin;Skin Temperature;Solid Neoplasm;Steroids;Symptoms;T-Lymphocyte;Testing;Therapeutic;Time;Transplant Recipients;Weight Gain

PROJECT_TITLE: Non-invasive assessment of graft vs host disease using optoacoustic imaging


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Cannabinoid Research;Chronic Pain;Clinical Research;Drug Abuse (NIDA only);Mental Health;Neurosciences;Pain Research;Pediatric;Prevention;Sleep Research;Substance Misuse;Telehealth

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative Pediatric chronic pain is a common, complex and highly debilitating developmental health concern that has been associated with multiple risk factors for heavy and frequent marijuana use. However, the longitudinal interplay among chronic pain and two key risk factors, sleep disturbances and decreased inhibitory control, as it relates to adolescent marijuana use, remains minimally explored. This study aims to map the unfolding of pathophysiological processes using a combination of mobile health assessment tools, in order to implement personalized, early intervention in these vulnerable adolescents.

PI_NAMEs: KOSSOWSKY, JOE  (contact)

PROGRAM_OFFICER_NAME: VIDAL, SARAH

PROJECT_TERMS: actigraphy;Adolescence;Adolescent;adolescent alcohol abuse;adolescent health;Adolescent marijuana use;adolescent patient;Adolescent Risk Behavior;adolescent substance abuse;adolescent substance use;Age;Alcohols;Area;Assessment tool;Award;Behavior;Cannabis;career;Cellular Phone;Characteristics;Childhood;chronic pain;chronic pain patient;circadian;circadian biology;Cognitive;cognitive testing;Collection;Complement;Complex;Data;Data Reporting;Development;digital;Dimensions;Drowsiness;Early Intervention;Ecological momentary assessment;Environment;Event;executive function;Frequencies;Funding;Goals;Grant;Health;health assessment;Health Technology;high risk;Impulsivity;Individual;Informatics;Interruption;Intervention;K-Series Research Career Programs;Life;Link;Maps;Marijuana;marijuana use;marijuana use disorder;marijuana user;Measurement;Mediating;Mental Health;Mentored Research Scientist Development Award;Mentors;Mentorship;Methods;mHealth;mobile application;Mobile Health Application;Modeling;neural network;Outcome;Pain;pain perception;pain symptom;patient oriented;Patient Self-Report;Patients;Phenotype;Polysomnography;Population;Positioning Attribute;preference;Process;prospective;Protocols documentation;public health priorities;Randomized, Controlled Trials;Reporting;Research;Research Personnel;Research Project Grants;responsible research conduct;Risk;Risk Factors;Risk Reduction;Risk Taking;Sampling;sensor technology;Severities;Sleep;Sleep Disorders;Sleep disturbances;sleep pattern;sleep quality;social;Stream;substance use;Techniques;Technology;Teenagers;Time;Training;United States;vulnerable adolescent;wearable device;Youth

PROJECT_TITLE: Mobile health applications in adolescent marijuana use: assessing the interplay among sleep, pain and inhibitory control

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Congenital Structural Anomalies;Genetics;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: Project Narrative Current studies of Marfan Syndrome (MFS) etiology, identification of potential early diagnostic markers, and development of non-invasive therapies have been hindered by animal models which fall short in to completely replicate signaling mechanisms in humans or provide a limited observational window of disease progression. Here, we propose to develop and utilize a patient-derived vascular graft as a novel in vitro model to study MFS. We anticipate understanding the underlying mechanism of vascular fragility and identify diagnostic markers or footholds for early therapeutic intervention for MFS.

PI_NAMEs: HALL, FRANKLYN  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: 3-Dimensional;Abnormal Cell;acetovanillone;Affect;Animal Model;Aorta;Apoptosis;Architecture;Behavior;Binding;Biocompatible Materials;Biological Assay;Blood Vessels;cell behavior;Cell Communication;Cells;Coculture Techniques;Collagen;Complex;Confocal Microscopy;Connective Tissue;Connective Tissue Diseases;Contractile Proteins;Data;Deposition;Development;diagnostic biomarker;Diameter;differentiation protocol;Disease;Disease Progression;Early Diagnosis;Elasticity;Elastin;Endothelial Cells;Endothelium;Enzyme-Linked Immunosorbent Assay;Etiology;Event;Exposure to;Extracellular Matrix;Extracellular Matrix Proteins;fastins;FBN1;fibrillin;Fibrin;Fibronectins;fibulin-4;Genes;Genetic Diseases;Genetic study;hemodynamics;Human;human induced pluripotent stem cells;Impairment;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;inhibitor;insight;interdisciplinary approach;Marfan Syndrome;Matrix Metalloproteinases;mechanical force;mechanical properties;mechanical signal;mechanical stimulus;Mechanics;Mediator;Methods;Microfibrils;MMP2 gene;MMP9 gene;Modeling;mouse model;Mutation;NADPH Oxidase 1;new therapeutic target;novel;overexpression;Paracrine Communication;Pathogenesis;Pathology;patient derived induced pluripotent stem cells;Patients;Perfusion;Phenotype;Physiological;pressure;Production;Property;protein expression;Reactive Oxygen Species;Regulation;response;scaffold;shear stress;Signal Transduction;Small Interfering RNA;Smooth Muscle Myocytes;Source;Tensile Strength;Testing;TGFB1 gene;Therapeutic;therapeutic development;Therapeutic Intervention;therapeutic target;Time;Tissues;Transgenic Mice;Tubular formation;Vascular Graft;Vascular Smooth Muscle

PROJECT_TITLE: Elucidating the Endothelial-Smooth Muscle Cell Interactions in Marfan Syndrome Using iPSCs


NIH_SPENDING_CATS: Digestive Diseases;Genetics;Human Genome;Microbiome;Nutrition;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: SAINT LOUIS

ORG_DEPT: PATHOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE  Proper lineage development and function of intestinal epithelium is critical to human health. Preliminary evidence suggests that epithelial PPARsignaling and fatty acid oxidation may be under the modulation of intestinal microbiota. This project will determine the mechanism of actions of how key members of human gut microbiota spatially shape epithelial differentiation and function along the crypt-villus axis and provide novel metabolites that have potential to impact intestinal health.

PI_NAMEs: WANG, YI  (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: ATAC-seq;bacterial community;Bangladeshi;Binding;Biological Assay;cell fate specification;Cell Lineage;Cell Nucleus;Cells;Child;Chromatin;Co-Immunoprecipitations;Collection;Colon;Communities;Data Set;Development;dietary;Duodenum;Eicosanoids;Enterocytes;Epigenetic Process;Epithelial Cells;Epithelium;Exclusion;experimental study;Exposure to;fatty acid metabolism;fatty acid oxidation;Fatty Acids;Genes;Genetic;Genome;Germ-Free;Gnotobiotic;Goals;Growth;gut health;gut microbes;gut microbiota;Health;HNF4A gene;Human;improved;In Situ Hybridization;Infant;insight;Intervention;intestinal epithelium;Intestines;Length;Ligands;liquid chromatography mass spectrometry;Malnutrition;Mediating;Mediator;member;Metabolic;microbial;microbiota;migration;Mothers;mouse genetics;mouse model;Mus;new therapeutic target;novel;Nuclear Receptors;Nucleic Acid Regulatory Sequences;Organoids;Pattern;Peroxisome Proliferator-Activated Receptors;pharmacologic;Physiology;Polyunsaturated Fatty Acids;postnatal;Prevotella;Process;programs;pup;receptor;Regulator Genes;Research;Resolution;response;Sampling;self-renewal;Shapes;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;Specific qualifier value;stem cells;System;Testing;Therapeutic;Tissue Harvesting;transcription factor;transmission process;two-dimensional;Villus;Work

PROJECT_TITLE: Key gut microbes shape intestinal epithelial lineage development, differentiation and metabolic function

STUDY_SECTION: DDK

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


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

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative As the burden of neurological disorders and neurodegenerative diseases in the United States and worldwide is high, there is a critical need to develop novel molecule imaging tools, such as PET ligands, to visualize and monitor pathophysiological processes in the brain. This work will develop key imaging ligands designed (1) to advance the scientific understanding of subtype-specific phosphodiesterase and its role in the pathophysiology and altered neuroimmune function of CNS diseases, including Alzheimer’s disease and related dementias; and (2) to enable target engagement studies and facilitate drug discovery of novel neurotherapeutics for Alzheimer’s patients.

PI_NAMEs: LIANG, STEVEN H (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: ABCB1 gene;abeta deposition;Affinity;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Amyloid beta-Protein;Autopsy;Autoradiography;Behavior;Binding;Binding Proteins;Biochemical Process;Biodistribution;Biological;Biological Assay;Biological Process;Blood specimen;Brain;brain tissue;Central Nervous System Diseases;Cerebellum;Characteristics;Chemistry;clinical translation;Corpus striatum structure;Cyclic AMP;design;Development;Docking;Dose;drug discovery;Enzymes;Evaluation;Exhibits;Family;Functional disorder;Generations;Goals;Human;Image;image translation;Imaging Device;Imaging ligands;imaging study;Immune response;immunoregulation;improved;In Vitro;in vivo;in vivo evaluation;Inflammatory Response;inhibitor;kinetic model;Kinetics;Knockout Mice;Knowledge;Label;Lead;Libraries;Ligands;lipophilicity;Liver Microsomes;Mediating;Memory;Metabolic Clearance Rate;Methylation;Molecular;molecular imaging;Monitor;mouse model;National Institute of Mental Health;Nervous System Disorder;Neurodegenerative Disorders;Neuroimmune;nonhuman primate;novel;Permeability;Pharmaceutical Chemistry;Pharmaceutical Preparations;phosphoric diester hydrolase;Plasma;Plasma Proteins;Play;Pontine structure;Positioning Attribute;Positron;Positron-Emission Tomography;Process;Radiolabeled;radioligand;Research;response;Rodent;Role;Scientific Advances and Accomplishments;Selection Criteria;Signal Transduction;Site;Specificity;tau-1;Testing;Toxic effect;transgenic model of alzheimer disease;Transgenic Organisms;Translations;United States;uptake;Validation;Visualization;Western Blotting;Work

PROJECT_TITLE: Subtype-selective phosphodiesterase PET ligands


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hematology;Liver Disease

ORG_CITY: Newark

ORG_DEPT: PHARMACOLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Chronic liver disease is a major contributor to morbidity and mortality worldwide, in part because there are no therapies to delay progression or promote resolution of hepatic fibrosis, the end stage pathology of chronic liver disease. Activation of the blood clotting cascade is associated with chronic liver disease progression, but the specific mechanisms linking clotting factors to deposition of scar tissue (i.e., collagen) in the injured liver are poorly understood. The primary goal of this research proposal is to uncover precisely how blood clotting factors interact with collagen-producing cells in the injured liver so that new therapies can be designed to delay the progression of liver fibrosis in patients.

PI_NAMEs: POOLE, LAUREN G (contact)

PROGRAM_OFFICER_NAME: DOO, EDWARD

PROJECT_TERMS: Agonist;Automobile Driving;Blood coagulation;Blood Coagulation Factor;Carbon Tetrachloride;career;Cell Physiology;Cells;chronic liver disease;chronic liver injury;Cicatrix;Clinical;Coagulation Process;Collagen;Deposition;design;Development;Discipline;Disease Progression;Event;Exogenous Factors;Factor VIIa;Factor XI;Factor XII;Foundations;Genetic;Goals;Hemostatic function;Hepatic Stellate Cell;Hepatology;hepatotoxin;In Vitro;in vivo;Inflammation;Intrinsic drive;Ligands;Link;Liver diseases;Liver Fibrosis;liver injury;Mediating;Membrane;Morbidity - disease rate;mortality;Mus;Mutant Strains Mice;Myofibroblast;new therapeutic target;novel;novel therapeutics;Outcome;PAR-1 Receptor;Pathologic;Pathology;Pathway interactions;Patients;Peptide Hydrolases;pharmacologic;Phenotype;Play;programs;Prothrombin;Publishing;receptor;Research;Research Personnel;Research Proposals;Resolution;Role;Scheme;Signal Transduction;skills;Testing;Thrombin;Thromboplastin;Thrombosis;tissue injury;Tissues;Toxicology;translational study;Up-Regulation

PROJECT_TITLE: Novel mechanisms linking blood coagulation to liver fibrosis


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: COLLEGE STATION

ORG_DEPT: BIOLOGY

ORG_NAME: TEXAS A&M UNIVERSITY

PHR: PROJECT NARRATIVE Changes in the genome structure due to copying, deletion, rearrangement, or otherwise reorganization of sequences is a major source of genetic variation in all organisms, including humans. Although structural variants cause many heritable diseases and underlie phenotypic changes, 40-80% of this genetic variation remains hidden to the common genotyping strategies. Here, we propose to create a comprehensive catalog of polymorphic structural genetic variation using 50 de novo platinum genome assemblies of genetically diverse D. melanogaster strains and investigate their fitness consequences using population genetic theories and experimental fitness assays.

PI_NAMEs: CHAKRABORTY, MAHUL  (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Affect;Biological Assay;Biological Process;Biological Sciences;California;career;Catalogs;Categories;causal variant;Classification;Complement;Complex;CRISPR/Cas technology;Data;Development;Disease;Drosophila genus;Drosophila melanogaster;Engineering;Ensure;experience;fitness;Frequencies;Gene Duplication;Generations;Genetic;Genetic Polymorphism;Genetic Variation;Genome;genome editing;Genome engineering;genome-wide;Genomic Segment;Genomics;Genotype;Grant;Heritability;Human;human disease;Human Genome;Individual;Link;Malignant Neoplasms;Maps;Measures;Mendelian disorder;Methods;model organism;Modeling;Molecular;Mutation;Natural Selections;Nicotine;Organism;Other Genetics;Oxidative Stress;Pattern;Pesticides;Phase;Phenotype;Platinum;Population Genetics;Positioning Attribute;Proxy;reference genome;Research;Resistance;Resources;response;Sampling Biases;Schizophrenia;Series;Site;SNP array;Source;Structure;theories;thermal stress;tool;Training;trait;Universities;Variant

PROJECT_TITLE: Evolutionary and functional consequences of structural genetic variation in Drosophila

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Brain Disorders;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Psychosis;Schizophrenia;Serious Mental Illness

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE This study will uncover the abnormalities in brain development that precede and predict the emergence of psychosis spectrum symptoms in youth. A detailed understand of such antecedent brain abnormalities is critical for early identification and intervention of disorders related to the psychosis spectrum, such as schizophrenia. Such knowledge would benefit public health by reducing the costs and burden of psychosis-related disorders on individuals and society at large.

PI_NAMEs: PARKES, LINDEN  (contact)

PROGRAM_OFFICER_NAME: PACHECO, JENNIFER LYNN

PROJECT_TERMS: Adolescent;Affect;Age;Award;biological heterogeneity;Biological Markers;biological sex;Brain;brain abnormalities;Clinical Data;clinically significant;cognitive development;cohort;Communication;Complex;control theory;cost;Coupled;Data;Data Set;Delusions;Development;Disease;dynamic system;Early identification;Early Intervention;emotion dysregulation;Female;follow-up;Goals;Graph;graph theory;gray matter;Growth;Hallucinations;indexing;Individual;insight;Knowledge;Learning;Link;Machine Learning;male;Maps;Measurement;Measures;Mediating;Mediation;Methods;model building;Modeling;multimodal neuroimaging;multimodality;network models;neurodevelopment;neuroimaging;neuroimaging marker;neuropsychiatry;Neurosciences;novel;Participant;Pathway interactions;Patients;Pattern;Persons;Phenotype;Philadelphia;Population;predictive marker;predictive modeling;prognostic;Prognostic Marker;Property;Psychiatry;Psychopathology;Psychoses;Public Health;Research;Rest;Risk;Risk Reduction;Sampling;Schizophrenia;Severities;sex;Sex Differences;social;Societies;Structure;Symptoms;Techniques;Time;tool;Training;Variant;white matter;Withdrawal;women versus men;Work;Youth

PROJECT_TITLE: Discovering prognostic neuroimaging biomarkers of the psychosis spectrum using network control theory


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Gene Therapy;Genetics;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE According to the American Brain Tumor Association, over 16,000 people are estimated to die from brain tumors this year while the currently available therapies cause motor and cognitive impairments and only extend life by 2 years. CAR T cell immunotherapy has the potential to improve outcomes in adult and pediatric brain tumor patients; however, optimized CAR design must be evaluated in models that closely mimic human disease and barriers for therapy. In this study, I propose using immune competent brain tumor models to enhance CAR T cell efficacy for brain tumors by optimizing CAR costimulatory domains, silencing negative T cell regulators, and targeting suppressive effectors of the brain tumor microenvironment including tumor associated macrophages.

PI_NAMEs: HAYDAR, DALIA  (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Adoptive Transfer;Adult;Adverse effects;American;Antigen Targeting;antigen-specific T cells;Antigens;antitumor effect;Biological;Brain Neoplasms;CAR T cell therapy;career;CBLB gene;CD276 gene;CD28 gene;Cell Cycle;Cell surface;Cells;Cellular immunotherapy;Chemotherapy and/or radiation;Childhood;Childhood Brain Neoplasm;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;Clinical Research;Core Facility;CRISPR screen;CRISPR/Cas technology;cytokine;cytotoxicity;design;Disease;Down-Regulation;engineered T cells;Engineering;exhaustion;extracellular;Gene Modified;Generations;Genes;Genetic;genome wide screen;Glioma;Goals;Hematologic Neoplasms;Heterogeneity;Homing;human disease;IL3RA gene;Image;Immune;immune cell infiltrate;Immune response;Immunocompetent;Immunology;Immunotherapy;Impaired cognition;Impairment;improved;improved outcome;In Vitro;in vitro activity;in vivo;Inflammatory;innovative technologies;interest;Intervention;Life;Macrophage;Mediating;Mediator;Memory;Modeling;Modification;Molecular;motor impairment;mouse model;Mus;Mutate;neoplastic cell;novel;Operative Surgical Procedures;Outcome;Patients;Penetration;Performance;Persons;Phase;Phenotype;Play;Positioning Attribute;Pre-Clinical Model;Primary Brain Neoplasms;Proliferating;prototype;receptor;Receptor Signaling;Research;research clinical testing;Research Personnel;Resistance;Role;Safety;Saint Jude Children's Research Hospital;Shapes;Subgroup;success;T-Cell Activation;T-Cell Homing Receptors;T-Cell Receptor;T-Lymphocyte;targeted treatment;TCR Activation;Techniques;Testing;tool;trafficking;Training;transcriptomics;Transmembrane Domain;tumor;Tumor Antigens;tumor microenvironment;tumor xenograft;Tumor-associated macrophages;tumor-immune system interactions;Xenograft Model

PROJECT_TITLE: Improving CAR T cell therapy for brain tumors using immune competent models


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Cost Effectiveness Research;HIV/AIDS;Health Services;Infectious Diseases;Mental Health

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE In South Africa, where 8 million persons are living with HIV, 56% are on ART, and only 45% are virally suppressed (the key indicator of treatment success) due to barriers to care including offering streamlined care only those persons demonstrating treatment success. To address this implementation gap, we propose to test the effect of adaptive differentiated service delivery by offering, in sequence, more tailored services to clients with detectable viral load and those not engaged in care. Working closely with the local HIV clinic, we will leverage ongoing changes in clinic practices to determine the impact of adapting the best clinic practices to include lottery incentives, community ART, and home ART delivery on viral suppression and cost-effectiveness at population level.

PI_NAMEs: BARNABAS, RUANNE VANESSA (contact);VAN HEERDEN, ALASTAIR

PROGRAM_OFFICER_NAME: STIRRATT, MICHAEL JAMES

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;antiretroviral therapy;arm;Back;barrier to care;Behavior;budget impact;care delivery;Caring;Cessation of life;Characteristics;Client;Clinic;Clinic Visits;Communities;cost;Cost Analysis;cost effectiveness;cost estimate;Cost Savings;Disease;Enrollment;Evaluation;experience;follow-up;Frequencies;Friends;Goals;Health Benefit;HIV;HIV Infections;HIV Seronegativity;HIV Seropositivity;Home;improved;incentive strategies;Incentives;Intervention;intervention delivery;Interview;Life;Measures;microcosting;Modeling;Morbidity - disease rate;mortality;Participant;patient-level barriers;peer;Persons;Population;preference;prevent;primary outcome;Provider;Randomized;randomized trial;recruit;Sampling;Sequential Multiple Assignment Randomized Trial;service delivery;Service provision;Services;South Africa;Subgroup;success;System;Testing;transmission process;treatment strategy;trial design;Viral;Viral Load result;Wages;Wait Time

PROJECT_TITLE: A sequential, adaptive model of differentiated service delivery to reach persons living with HIV who are lost-to-follow-up or who have detectable viral load

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: NEW YORK

ORG_DEPT: PHYSIOLOGY

ORG_NAME: ROCKEFELLER UNIVERSITY

ORG_STATE: NY

PHR: Project Narrative We propose to characterize the transcription cycle structurally and functionally in the actinobacteria phylum, focusing on the pathogen Mycobacterium tuberculosis. RNA polymerase, the central enzyme of transcription, is a proven target for antimicrobials, and regulators of the transcription cycle are often clade-specific but essential for viability and virulence. Understanding how these factors regulate Mycobacterium tuberculosis RNA polymerase informs us on unified and clade-specific mechanisms, providing a more comprehensive understanding of the transcription cycle that can lead to new therapeutics against specific bacterial pathogens.

PI_NAMEs: CAMPBELL, ELIZABETH A (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Actinobacteria class;Antibiotic Resistance;Antibiotics;antimicrobial;Bacteria;Biochemical;Biological;Biophysics;Cell Physiology;Cells;Cessation of life;Complex;Coupling;Cryo-electron tomography;Cryoelectron Microscopy;DNA Sequence;DNA-Directed RNA Polymerase;Enzymes;Escherichia coli;experimental study;Funding;Genetic;Genetic Transcription;genome-wide;Genomic DNA;Genomics;Genus Mycobacterium;global health;In Situ;interdisciplinary approach;Methods;Molecular;mycobacterial;Mycobacterium tuberculosis;novel therapeutics;particle;pathogen;pathogenic bacteria;pleiotropism;Regulation;Regulator Genes;Regulon;Reporting;Resolution;response;Ribosomes;Rifampin;RNA Polymerase Inhibitor;RNA purification;Role;Signal Transduction;Stress;Structure;Transcript;transcription factor;Transcription Initiation;transcriptome sequencing;Tuberculosis;tuberculosis treatment;Virulence;Vision

PROJECT_TITLE: Structural and functional studies of the mycobacterial transcription cycle

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MRAF-C (01)]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Cardiovascular;Childhood Obesity;Climate-Related Exposures and Conditions;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: Aurora

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Exposure to air pollution from traffic early in life may increase the risk of childhood obesity. We will examine whether maternal and child exposure to a traffic-related component of air pollution, black carbon, promotes higher adiposity, overweight, and obesity and changes to markers of cardiometabolic risk. If associations are identified, results will inform a comprehensive evaluation of the health risks associated with traffic-related air pollution exposure to pregnant women and children.

PI_NAMEs: FRIEDMAN, CHLOE S (contact)

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: 6 year old;8 year old;adipokines;adiponectin;Adipose tissue;Adult;adverse birth outcomes;Age;aged;Air;Air Pollutants;Air Pollution;ambient air pollution;Area;Biological;Biological Markers;biomarker panel;Birth;Blood;Body Composition;Body mass index;Body measure procedure;Body Weight;Brain;Carbon Black;Cardiometabolic Disease;cardiometabolic risk;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;career;career development;Chemicals;Child;Childhood;Chronic Disease;cohort;Cohort Studies;Colorado;Complex;Data;Diabetes Mellitus;Diameter;Dietary Factors;disorder risk;doctoral student;early childhood;early life exposure;Enrollment;Environment;environmental chemical;Environmental Epidemiology;Environmental Exposure;Environmental Impact;Environmental Policy;Environmental Pollutants;Epidemiologic Methods;epidemiology study;ethnic diversity;Evaluation;Exposure to;Faculty;fasting glucose;Fatty acid glycerol esters;fine particles;Glucose;Goals;Growth;Health;Heterogeneity;high risk;Homeostasis;improved;indexing;Institution;Insulin;Insulin Resistance;International;Knowledge;Leptin;Life;Life course epidemiology;Life Cycle Stages;Link;Lipids;Literature;longitudinal analysis;Measurement;Measures;Medical;Mentorship;Metabolic;Metabolic Diseases;meter;Methodology;Methods;metropolitan;Modeling;modifiable risk;mortality;Motor Vehicles;Nature;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;obesity in children;obesity risk;offspring;Outcome;Overweight;Participant;Particulate Matter;Phenotype;Placenta;Play;Plethysmography;Policies;Policy Maker;pollutant;Postdoctoral Fellow;postnatal;predictive modeling;Pregnancy;Pregnant Women;prenatal;Prevalence;Productivity;Public Health;Research;Research Design;research facility;Research Personnel;Research Project Grants;Resource Development;Risk;Risk Factors;Role;Scientist;sedentary lifestyle;skills;Source;spatiotemporal;Statistical Models;Techniques;Toxic effect;traffic-related air pollution;Training;Universities;Vehicle Emissions;waist circumference;Work

PROJECT_TITLE: Prenatal and early-life black carbon exposure and childhood cardiometabolic health

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F18-D(20)L]


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: Project Narrative  The mechanisms of sex determination are an important and complex medical issue that involves multiple interacting cell types, several organs, and impacts susceptibility to disease, psychological development, and sense of person. We lack, however, full knowledge of how various genetic factors interact with the environment and its contaminants to direct sex determination. Because zebrafish is an important medical model with a sex- determination system that is sensitive to unidentified genetic variation and poorly understood environmental influences, we propose a research program to discover the developmental genetic basis for zebrafish sex determination.

PI_NAMEs: POSTLETHWAIT, JOHN H. (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Bacterial Artificial Chromosomes;Biological Assay;Body System;Cell Communication;cell type;Cells;Chromosomes;Complex;CRISPR/Cas technology;Development;developmental genetics;Disease;Disease susceptibility;dosage;Dose;Environment;Environmental Risk Factor;experimental study;Female;Fishes;Gene Expression;gene interaction;Gene Transfer Techniques;Genes;Genetic;Genetic Polymorphism;Genetic Recombination;Genetic Variation;Genome;Genotype;Goals;Human;India;insertion/deletion mutation;Knock-out;Knowledge;Learning;male;Medical;Meiosis;Minority;Modeling;Molecular;Molecular Genetics;mutant;Mutation;neuronal cell body;non-genetic;Oocytes;Organ;Pathway interactions;Persons;Predisposition;programs;psychologic;Research;sex;sex determination;Sexual Development;Signal Transduction;single-cell RNA sequencing;Specific qualifier value;System;Vision;Work;Zebrafish

PROJECT_TITLE: Mechanisms of Sex Determination in Zebrafish

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


NIH_SPENDING_CATS: Biotechnology;Genetics;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: MINNEAPOLIS

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: Project Narrative The failure of proper termination of tissue regeneration results in the emergence of unwanted cells, leading to abnormal organ size and a high risk of cancer. However, the mechanisms by which stem cell proliferation is precisely controlled during the course of regeneration are poorly understood. The proposed study is designed to define the molecular mechanisms that function for stem cell inactivation and the extracellular matrix remodeling at the regeneration termination stage using the Drosophila midgut intestinal stem cell model.

PI_NAMEs: NAKATO, HIROSHI  (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Actins;Activins;Affect;Bacterial Infections;Biological Models;Cells;Complex;Data;design;Drosophila genus;Dystroglycan;Dystrophin;ECM receptor;Epithelium;Extracellular Matrix;Failure;Filopodia;Foundations;Future;gastrointestinal system;Gene Silencing;Genes;Genetic;gliotactin;Glycoproteins;helicase;Heparan Sulfate Proteoglycan;High-Risk Cancer;Homeostasis;Integrins;Intestines;Knowledge;Link;Mediating;member;Membrane;Messenger RNA;MicroRNAs;Midgut;Mitotic Activity;Modeling;Molecular;Natural regeneration;Nature;Order Coleoptera;Organ Size;Papio;Pathway interactions;Phase;Process;regenerative tissue;response;Role;Septate;Signal Transduction;Stem Cell Development;stem cell function;stem cell model;stem cell proliferation;stem cell therapy;stem cells;syndecan;targeted cancer therapy;Testing;tissue regeneration;tissue repair;Tissues;tool;transcriptome sequencing;tumor;Type I Activin Receptors

PROJECT_TITLE: Molecular Mechanisms of Regeneration Termination

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


ADMINISTERING_IC: OH

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_CITY: Atlanta

ORG_NAME: COUNCIL OF STATE & TERRITORIAL EPIDEM

PHR: The overall goal of the Western States Occupational Network (WestON) meeting is to strengthen state-based occupational epidemiology in the Western region through capacity building and scientific collaboration, including the ongoing surveillance of work-related injuries and diseases, investigation of cases and outbreaks, and dissemination of information for public health prevention. The WestON meeting aligns with several NIOSH NORA Sector and Cross-Sector Program goals, including Agricultural, Forestry and Fishing (AFF); Mining; Oil and Gas Extraction; Health Hazard Evaluation; and Surveillance.

PI_NAMEs: HARRISON, ROBERT J (contact)

STUDY_SECTION: SOH

STUDY_SECTION_NAME: Safety and Occupational Health Study Section[SOH]


NIH_SPENDING_CATS: Asthma;Lung

ORG_CITY: RICHMOND

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Narrative The proposed studies will reveal how dendritic cells utilize environmental signals from allergens to alter energy metabolism towards glutaminolysis that results in T follicular helper13 (Tfh13) stimulation. Tfh13 induction leads to allergen-specific IgE production and a pro-asthmatic state. Moreover, this work promises an exciting new avenue for allergic sensitization reversal by inhibiting glutaminolysis.

PI_NAMEs: MARTIN, REBECCA KELLEY (contact)

PROGRAM_OFFICER_NAME: LU, JINING

PROJECT_TERMS: Affinity;airborne allergen;airway hyperresponsiveness;Allergens;Allergic;alpha ketoglutarate;Antibodies;Antigen Presentation Pathway;Antigens;Asthma;asthma model;asthmatic;B-Lymphocytes;Biological Assay;Blood;Bronchoconstriction;Carbon;Cell Nucleus;Cells;Chronic;Chronic lung disease;chronic respiratory disease;Citric Acid Cycle;clinical translation;cytokine;Data;demethylation;Dendritic Cells;Development;Disease;Effector Cell;Energy Metabolism;environmental allergen;Enzymes;Exhibits;extracellular;Extrinsic asthma;fatty acid oxidation;Flow Cytometry;Fumarates;Gene Expression;Genetic Transcription;Glucose;Glutaminase;Glutamine;Goals;Helper-Inducer T-Lymphocyte;high dimensionality;Human;Hypersensitivity;IgE;In Vitro;in vivo;Inflammation;inhibitor;Knowledge;Label;Lung;Malates;mast cell;Mediastinal lymph node group;Metabolic;Metabolism;metabolomics;migration;Mus;new therapeutic target;O Antigens;Pathway interactions;polarized cell;Prevalence;Prevention strategy;Production;programs;Pulmonary Inflammation;Regulation;response;Signal Transduction;Stimulus;Succinates;T-Lymphocyte;Testing;Tonsil;transcriptome sequencing;Work

PROJECT_TITLE: Metabolic perturbations in conventional dendritic cells modulate Tfh13 induction in asthmatic sensitization

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Heart Disease;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: RESEARCH TRIANGLE PARK

ORG_NAME: RESEARCH TRIANGLE INSTITUTE

PHR: PROJECT NARRATIVE Cardiovascular disease (CVD) is the leading cause of illness and death in U.S. women at all ages, and although it has been linked to earlier difficult pregnancies, we lack the strong evidence about the causes of CVD in women that is needed to guide effective clinical prevention strategies. To optimize CVD risk prediction and prevention strategies for women, we propose to continue follow-up of the nuMoM2b Heart Health Study cohort, a diverse group of 4,475 women enrolled starting 7 years ago during their first pregnancy. Continuing to follow these women—building on a foundation of high-quality data and biospecimens collected under a regulatory framework that allows responsible sharing among vetted scientists, and taking advantage of an existing robust administrative and scientific framework—provides what we believe to be a unique opportunity for scientists to understand how CVD starts and develops in women.

PI_NAMEs: GREENLAND, PHILIP ;MCNEIL, REBECCA BOEHM (contact);SAADE, GEORGE R.

PROGRAM_OFFICER_NAME: BURNS, KRISTIN

PROJECT_TERMS: Address;adverse pregnancy outcome;Age;Ancillary Study;Behavioral;Biometry;Birth;Cardiac health;Cardiology;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;Cerebrovascular Disorders;Cessation of life;Clinical;Clinical Data;cohort;Cohort Studies;Data;Data Collection;Development;Diabetes Mellitus;Early identification;Enrollment;Environment;ethnic diversity;Ethnic Origin;experience;follow-up;Foundations;Future;Geography;Gestational Diabetes;Goals;Grant;Hypertension;Incidence;Incidence Study;indexing;Infrastructure;infrastructure development;Investigation;Kidney Diseases;Knowledge;Leadership;Link;Maternal-fetal medicine;Mediating;Metabolic syndrome;Morbidity - disease rate;mortality;multimodality;nutrition;Obesity;Observational Study;patient engagement;Pattern;Persons;Phenotype;Physical activity;post pregnancy;Pregnancy;Pregnancy Complications;pregnancy hypertension;Premature Birth;Prevention;Prevention strategy;Process;prospective;Recurrence;reproductive;Resource Sharing;Resources;Risk Factors;risk prediction;Schedule;Scientist;Sleep Apnea Syndromes;Small for Gestational Age Infant;Smoking;stillbirth;Structure;success;Time;treatment strategy;United States;United States National Institutes of Health;Visit;Woman;women's morbidity;Women's mortality

PROJECT_TITLE: Continuation of the NuMoM2b Heart Health Study


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Kidney Disease;Prevention;Racial and Ethnic Minority Health Research

ORG_NAME: TUFTS MEDICAL CENTER

PHR: NARRATIVE Estimated glomerular filtration rate and urine albumin-to-creatinine ratio, measures of glomerular function and injury respectively, are currently used to stage chronic kidney disease. Novel urine measures that quantify the health of the kidney tubules have recently allowed us to define additional dimensions of kidney health. Our global hypothesis with this application is that kidney tubule damage and dysfunction are related to the onset and progression of atherosclerotic cardiovascular disease and heart failure.

PI_NAMEs: GUTIERREZ, ORLANDO M;IX, JOACHIM H;SARNAK, MARK J (contact);SHLIPAK, MICHAEL G

PROGRAM_OFFICER_NAME: MUSSOLINO, MICHAEL EUGENE

PROJECT_TERMS: absorption;Address;adverse outcome;Age;Age Years;Albumins;Albuminuria;Aldosterone Antagonists;Ankle;Atherosclerosis;atherosclerosis risk;Biological Markers;biomarker panel;Black Populations;Black race;blood glucose regulation;Blood Pressure;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular system;Cessation of life;Chronic Kidney Failure;Cicatrix;Clinical;clinical risk;clinically relevant;cohort;Cohort Studies;Communities;coronary artery calcification;Coronary Artery Risk Development in Young Adults Study;Creatinine;Cross-Sectional Studies;Development;Dietary intake;Dimensions;Disease;Disease Marker;Dyslipidemias;Elderly;ethnic difference;Event;experience;Fibrosis;Functional disorder;Future;General Population;Glomerular Filtration Rate;glomerular function;Goals;Health;Heart failure;high risk;high risk population;Hispanic Populations;HIV Infections;Homeostasis;improved;Incidence;indexing;Individual;inhibitor;Injury;insight;intimal medial thickening;Kidney;kidney biopsy;Kidney Diseases;Kidney Failure;Kidney Transplantation;Left Ventricular Mass;Life;longitudinal analysis;Measures;middle age;Monitor;Morbidity - disease rate;mortality;mortality risk;Multi-Ethnic Study of Atherosclerosis;Myocardial Infarction;National Institute of Diabetes and Digestive and Kidney Diseases;nephrogenesis;new therapeutic target;novel;Obesity;older adult;Pathology;Pathway interactions;Persons;physical inactivity;Population;Prevention strategy;Primary Prevention;prognostic;Prognostic Factor;racial difference;Renal function;Renal tubule structure;repaired;Research;Risk;Risk Factors;Risk Reduction;Role;screening;Smoking;Specimen;Standardization;Stroke;Structure;Transplant Recipients;treatment strategy;Tubular formation;Urine

PROJECT_TITLE: Dimensions of Kidney Tubule Health and Atherosclerotic Cardiovascular Disease and Heart Failure in Middle-Aged and Older Adults

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: HIV/AIDS;Mental Health;Prevention;Social Determinants of Health

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Despite major advances in the care and treatment for people living with HIV (PLHIV), morbidity and mortality among PLHIV remains unacceptably high in sub-Saharan Africa, largely due to the parallel challenges of poverty and food insecurity. The proposed Sustainable Development for HIV Health (SD4H) Training Program aims to train a cadre of interdisciplinary Kenyan PhD and Masters students' at Maseno University who will work at the intersection of sustainable development and health with a focus on improving HIV care, treatment and prevention outcomes. The proposed structure of the program supports young investigators to remain in Kenya because students remain vested and actively engaged in studies and meet the requirements for a degree within their home institution while benefiting from enhancements, i.e. additional courses/certificate offered at participating University of California campuses, full-participation in a SD4H mentored-research experience and a multidisciplinary team of dedicated mentors from Maseno University, the Kenya Medical Research Institute and the UC Global Health Institute.

PI_NAMEs: BUKUSI, ELIZABETH ANNE;COHEN, CRAIG R (contact);NDUNYU, LOUISA ;WEISER, SHERI DAWN

PROGRAM_OFFICER_NAME: BANSAL, GEETHA PARTHASARATHY

PROJECT_TERMS: Address;Affect;Africa South of the Sahara;Agriculture;Biological Sciences;California;Career Mobility;Clinical Research;Collaborations;Community Health;design;Development;Discipline;Discipline of Nursing;Doctor of Philosophy;doctoral student;Economics;Education;Educational workshop;Environmental Science;evidence base;experience;Faculty;faculty mentor;food insecurity;food security;Gender;global health;Health;Health Professional;health training;HIV;HIV/AIDS;improved;innovation;Institution;International;Intervention;Kenya;low and middle-income countries;Medical Research;Medicine;Mentors;Mentorship;Morbidity - disease rate;mortality;next generation;nutrition;online course;Outcome;Persons;Play;Policies;Population;Poverty;poverty alleviation;Prevention;programs;Public Health;Research;Research Institute;Research Personnel;Research Support;Role;Science;Scientist;Social Sciences;Students;Sustainable Development;synergism;Training;Training Programs;Training Support;United States;Universities;university student

PROJECT_TITLE: Sustainable Development for Improved HIV Health and Prevention in Kenya (SD4H-Kenya)


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Immunotherapy;Orphan Drug;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE This application seeks to develop biomarkers of response to immunotherapy in head and neck cancers. We propose to develop unique biomarkers that identify the cells that inhibit the immune attack of the cancer and predict which patients will and will not benefit from immune therapy, as well as guide development of novel drugs based on detailed knowledge of immune phenotypes in patients who respond poorly to treatment.

PI_NAMEs: CHRISTENSEN, BROCK CLARKE;KELSEY, KARL TIMOTHY (contact)

PROGRAM_OFFICER_NAME: BHARTI, SANITA

PROJECT_TERMS: Address;Adverse event;Biological Markers;biomarker identification;Blood;blood treatment;Bone Marrow;Cancer Patient;cancer type;Cell Separation;cell type;Cells;checkpoint therapy;chemotherapy;Clinical;clinical application;clinical decision-making;Clone Cells;cohort;Comprehensive Cancer Center;cost effective;Cryopreservation;Data;Development;Disease;Disease remission;DNA;DNA Methylation;Drug Costs;Epigenetic Process;epigenome-wide association studies;Evaluation;Fingerprint;Funding;Generations;granulocyte;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Hematopoiesis;Human;Immune;immune checkpoint blockade;immune modulating agents;Immune response;Immune system;Immunologic Markers;Immunologic Techniques;immunological status;Immunologics;immunomodulatory therapies;Immunophenotyping;Immunotherapeutic agent;Immunotherapy;improved;in vivo;Individual;Inflammation;innovation;Knowledge;Leukocytes;Libraries;Lymphocyte;Malignant Neoplasms;Measures;Mediating;Methodology;Methylation;methylomics;monocyte;Mutation;Myeloid-derived suppressor cells;Myelopoiesis;Nature;neutrophil;Nivolumab;novel;novel marker;novel therapeutics;patient response;Patient-Focused Outcomes;Patients;Pattern;pembrolizumab;Peripheral;peripheral blood;Phenotype;phenotypic biomarker;Population;Prediction of Response to Therapy;predictive marker;Predictive Value of Tests;Production;Prognosis;prognostic;Prognostic Marker;prognostic value;programmed cell death ligand 1;Property;prospective;Prospective Studies;Recurrence;Recurrent disease;Reproducibility;response;response biomarker;Retrospective Studies;Risk;Role;Site;Standardization;Stratification;survivorship;Therapeutic Agents;Time;tool;treatment duration;treatment response;tumor;Tumor Immunity;tumor microenvironment;Unresectable;Work

PROJECT_TITLE: DNA-based Immune Phenotyping in HNSCC for Biomarkers of Response to Immunotherapy


NIH_SPENDING_CATS: Cancer;Rare Diseases

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Ferroptosis is an iron-dependent, oxidative form of regulated cell death that is morphologically and biochemically distinct from other cell death pathways, and has been implicated in numerous cancer therapies and natural tumor suppression mechanisms. This proposal will utilize small molecule and lipid probes, genetic modulation techniques, lipidomic profiling and activation state assays to investigate the roles of lipid remodeling and lipid-responsive signaling pathways in mediating ferroptotic cell death. Building a more comprehensive model of the molecular networks involved in ferroptosis may uncover new avenues of research to exploit this cell death pathway for therapeutic benefit in cancer.

PI_NAMEs: LIN, ANNIE J (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: ABHD12 gene;acquired drug resistance;Address;anti-cancer;BAY 54-9085;Biochemical;Biological;Biological Assay;Biological Models;cancer cell;Cancer cell line;cancer therapy;Cell Death;Cell Death Induction;Cell Survival;cell type;Cells;Cessation of life;chemotherapeutic agent;Conventional (Clear Cell) Renal Cell Carcinoma;CRISPR/Cas technology;Degenerative Disorder;Dependence;Development;Diglycerides;Dose;Drug Metabolic Detoxication;Enzymes;epithelial to mesenchymal transition;Equilibrium;Etiology;Event;Excision;Exhibits;Fatty Acids;fibrosarcoma;Genes;Genetic;glutathione peroxidase;Heart;Human;immune checkpoint blockade;In Vitro;in vivo;inhibitor;Investigation;Iron;Isoenzymes;kinase inhibitor;knock-down;lipid mediator;Lipid Peroxidation;lipidome;lipidomics;Lipids;Lysophospholipids;Malignant Neoplasms;Mammals;Mediating;Mediator;Membrane;Modality;Molecular;molecular modeling;Morphology;neoplastic cell;network models;novel;Oxidation-Reduction;oxidative damage;Oxidative Stress Pathway;Participant;Pathway interactions;Pharmacotherapy;Phospholipase;Phospholipase A2;Phospholipids;Physiological;Play;Polyunsaturated Fatty Acids;Positioning Attribute;Predisposition;Primary carcinoma of the liver cells;Process;protein activation;Protein Family;Protein Isoforms;Protein Kinase;Protein Kinase C;Reactive Oxygen Species;repaired;Reporting;Research;response;Role;Shapes;Signal Induction;Signal Pathway;Signal Transduction;small hairpin RNA;Small Interfering RNA;small molecule;Specificity;Stress;Techniques;Testing;Therapeutic;therapeutic development;therapy resistant;Time;Tumor Suppression;Up-Regulation

PROJECT_TITLE: Investigating the Roles of Phospholipase A2s and Diacylglycerol Signaling in Ferroptosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-U(20)L]