PHR: PROJECT NARRATIVE Bacteriophage therapy is a promising new therapy for bacterial infections, including periprosthetic joint infection. The objective of this proposal is to determine how changes in Staphylococcus aureus wall teichoic acid glycosylation vary under different conditions and impact phage activity. This will contribute to our long-term goal to develop new treatment strategies for periprosthetic joint infection which includes an ongoing, independently funded FDA Phase II/III study.

PI_NAMEs: DOUB, JAMES B.;URISH, KENNETH L (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Address;Antibiotics;Bacteria;Bacterial Infections;Bacteriophages;Binding;Biological Assay;Bioreactors;bone;Case Series;Chronic;Clinical;Clinical Research;Complication;Culture Media;Data;Effectiveness;Enrollment;Environment;Failure;FDA approved;Funding;Future;glycosylation;Goals;Growth;Guidelines;Histologic;Implant;improved;In Vitro;in vitro activity;in vivo;knee replacement arthroplasty;Knowledge;Libraries;Malignant Neoplasms;Measures;Methods;Microbial Biofilms;mortality;novel strategies;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Organism;Outcome;Pathway interactions;Patient Isolation;Patients;Pattern;peptidoglycan receptor;Periprosthetic joint infection;Phase;Phenotype;Population;Process;Protocols documentation;receptor;Reproducibility;Role;Safety;screening;Series;Site;soft tissue;Staphylococcus aureus;success;Surface;Synovial Fluid;Teichoic Acids;Testing;Therapeutic;tissue culture;Tissues;Treatment Protocols;United States;Variant;Virus;Work

PROJECT_TITLE: The Role of Teichoic Acid Glycosylation in Phage Activity and Selection in an Ongoing FDA Phase II/III Clinical Study of Bacteriophage Therapy in Chronic Periprosthetic Joint Infection


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Genetics;Immunotherapy;Precision Medicine;Prostate Cancer;Urologic Diseases;Women's Health Research

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: Project Narrative Our Research Program incorporates powerful combinations of mouse genetic models, pharmacology, patient- derived tumor models, and new developments in immuno-oncology to bring about tangible advances in cancer therapy and patient care. Specifically, we propose to build upon our success in developing effective treatments against specific subtypes of cancer and brain metastases by harnessing the power of the immune system to potentiate therapeutic strategies aimed to achieve long-term survival. The research we propose has the potential to significantly enhance response to therapy and decrease the development of therapeutic resistance.

PI_NAMEs: ZHAO, JEAN  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Affect;anti-tumor immune response;Biological Process;Brain;Cancer Biology;Cancer Patient;cancer subtypes;cancer therapy;Cell Physiology;Cells;clinical development;clinically relevant;Development;Disease;effective therapy;experience;Family;Genetic Models;Genetically Engineered Mouse;Goals;Immune;Immune Evasion;Immune response;Immune system;Immunomodulators;Immunooncology;Immunotherapeutic agent;Immunotherapy;Laboratories;Malignant Breast Neoplasm;Malignant neoplasm of prostate;Malignant Neoplasms;Metastatic malignant neoplasm to brain;Modeling;Molecular;mouse genetics;mouse model;multiple omics;Neoplasm Metastasis;new technology;novel;Oncogenic;Patient Care;patient derived xenograft model;Patients;Pharmacology;PIK3CG gene;pre-clinical;programs;PTEN gene;Research;response;Role;Shapes;Signal Transduction;success;targeted treatment;Therapeutic;therapeutic development;therapy outcome;therapy resistant;Translational Research;treatment response;treatment strategy;tumor;tumorigenesis

PROJECT_TITLE: Integrating targeted therapy and immunotherapy to break through cancer


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Rare Diseases

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: Project Narrative The goal of this project is to develop a novel MRI-compatible robotic system for brain tumor biopsy and ablation. The proposed robotic system with an integrated MR imaging coil would enable in-bore real-time image-guided tumor biopsy and ablation. This platform would increase the targeting accuracy and safety of the procedures and reduce the procedure time to enable better patient care.

PI_NAMEs: MONFAREDI, REZA  (contact)

PROGRAM_OFFICER_NAME: BITTMANN, MORIA FISHER

PROJECT_TERMS: Ablation;Address;Anesthesia procedures;Area;Arthroscopy;Biopsy;blind;Brain;Brain imaging;Brain Neoplasms;Cadaver;Cephalic;Child;Childhood;Clinical;clinical development;Clinical Research;Complex;Complication;Consumption;cost;cranium;Death Rate;design;Development;Devices;Diagnostic Procedure;Disease;Ensure;Epilepsy;experience;Freedom;Funding;Goals;Head;Hemorrhage;Hospitals;Hour;Human;Image;image guided;image guided intervention;Image-Guided Surgery;imaging modality;improved;Injections;instrument;interest;Intervention;Magnetic Resonance Imaging;Manuals;Maps;Medical center;Medical Device;Methods;Morbidity - disease rate;Needle biopsy procedure;Needles;Neoplasm Metastasis;Neurosurgeon;neurosurgery;Neurosurgical Procedures;novel;operation;Operative Surgical Procedures;Outcome;Pain;Parkinson Disease;Patient Care;Patients;Pediatric Hospitals;Phase;Planning Techniques;Positioning Attribute;Postoperative Hemorrhage;procedure safety;Procedures;real-time images;Research;Rewards;Risk;Risk Reduction;Robot;robotic system;Robotics;Safety;soft tissue;Structure;Surgeon;System;Techniques;Technology;technology platform;Testing;Time;tumor;United States;United States National Institutes of Health;Validation;Visualization;Work;X-Ray Computed Tomography

PROJECT_TITLE: MRI-Compatible Robot for Real-Time Image-Guided Stereotactic Neurosurgical Procedures: A Novel Platform Technology

STUDY_SECTION: BTSS

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


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Depression;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Mental Illness;Pediatric;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Suicide;Suicide Prevention;Telehealth

ORG_CITY: CORAL GABLES

ORG_NAME: UNIVERSITY OF MIAMI CORAL GABLES

ORG_STATE: FL

PHR: PROJECT NARRATIVE This study will evaluate the effectiveness of an online adaptation of a parenting program delivered in primary care for Hispanic youth in preventing/reducing depressive and anxiety symptoms as well as in reducing suicide behavior. It will also examine the factors that facilitate or impede the integration of this parenting program in primary care. The knowledge expected to be gained in this study has the potential to transform the way prevention programs aimed at promoting mental health are delivered in primary care settings.

PI_NAMEs: BROWN, C. HENDRICKS;PRADO, GUILLERMO  (contact)

PROGRAM_OFFICER_NAME: ROONEY, MARY

PROJECT_TERMS: 17 year old;Adolescence;Adolescent;adolescent health;adolescent mental health;Adoption;Adult;Affect;Age;Anxiety;anxiety symptoms;Behavior Therapy;Child;Child Rearing;Childhood;Chronic;Clinic;Communication;communication behavior;cost effective;depressive symptoms;design;Development;Disease;disparity reduction;drug abuse prevention;drug misuse;Drug usage;drug use behavior;Early Intervention;Education;effectiveness evaluation;eHealth;emerging adult;Employment;Engineering;ethnic minority;evidence base;experience;externalizing behavior;Family;Feeling suicidal;Goals;Health;health disparity;Health Insurance;Hispanic;hybrid type 1 trial;ideation;Impairment;implementation process;implementation/effectiveness;improved;Interruption;Intervention;intervention delivery;intervention effect;Knowledge;Latinx;maladaptive behavior;Mediating;Medicine;Mental Depression;Mental disorders;Mental Health;Mental health promotion;minority children;Not Hispanic or Latino;Outcome;parenting intervention;Participant;Pathway interactions;peer;prevent;Prevention;Prevention program;preventive intervention;Primary Care;primary care setting;programs;protective factors;Provider;Psyche structure;Randomized;Recording of previous events;reduce symptoms;reducing suicide;Reporting;Research;Resources;Risk Factors;Schools;Severities;Sexually Transmitted Diseases;single episode major depressive disorder;social;socioeconomic disadvantage;standard of care;statistics;Substance Use Disorder;suicidal behavior;Suicide attempt;Symptoms;System;Testing;theories;therapy design;Time;United States National Academy of Sciences;Youth

PROJECT_TITLE: Scaling a Parenting EBI for Latinx Youth Mental Health in Primary Care


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;Genetics;Mental Health;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES

ORG_STATE: WA

PHR: Project Narrative Opioid addiction is a chronic, progressive disorder that has led to an epidemic of deaths due to overdose. The severity of the opioid withdrawal syndrome is a major disincentive for individuals to attempt to stop opioid use. Therefore, developing new methods of mitigating the opioid withdrawal syndrome will not only alleviate these severe symptoms but may assist addicts in making the decision to discontinue opioid abuse.

PI_NAMEs: NEUMAIER, JOHN F (contact)

PROGRAM_OFFICER_NAME: TSAI, SHANG-YI ANNE

PROJECT_TERMS: 3-Dimensional;Abstinence;Analgesics;Animals;antagonist;Anxiety;Award;Behavior;Behavioral;Behavioral Model;Binding;Biosensor;Brain;brain research;Calcium;Cells;Cessation of life;Chronic;common symptom;Complex;Complication;confocal imaging;Confocal Microscopy;Corpus striatum structure;Cyclic AMP;Decision Making;Dependence;designer receptors exclusively activated by designer drugs;Disease;Disease remission;Disincentive;drug craving;Emotional;Emotions;Epidemic;Face;Fentanyl;fentanyl exposure;fentanyl self-administration;fentanyl use;Fluorescence Resonance Energy Transfer;Genetic;glial activation;Goals;Grant;Harvest;Hyperalgesia;Immune;In Vitro;Individual;Inflammatory;Injections;Investigation;Learning;LoxP-flanked allele;Measures;Mediating;Messenger RNA;Methods;Microglia;Microscopy;Modeling;Molecular;Morphine;Morphology;Motility;Mus;Naloxone;Narcotics;Nature;negative emotional state;Negative Reinforcements;Neuroglia;neuroinflammation;Neurons;neurotransmission;novel therapeutics;Opiate Addiction;opiate tolerance;Opioid;opioid abuse;opioid epidemic;opioid overdose;Opioid Receptor;opioid use;opioid withdrawal;Oral;Overdose;overdose death;Pharmaceutical Preparations;Phase;Physical assessment;Procedures;Process;Purinoceptor;receptor;recruit;Relapse;Reporter;response;Rest;Rewards;Ribosomes;RiboTag;RNA;Role;Severities;Signal Transduction;Slice;Structure;Substance Withdrawal Syndrome;Symptoms;Testing;Time;transcriptome sequencing;Transgenic Mice;Translations;translatome;two-photon;Withdrawal;Withdrawal Symptom

PROJECT_TITLE: Microglia and Opioid Withdrawal: Mechanisms of Negative Reinforcement

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


ADMINISTERING_IC: AI

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Clinical Research;Heart Disease;Hematology;Infectious Diseases;Rare Diseases

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE This project explores the mechanisms by which streptococci produce endocarditis, a life-threatening infection of heart valves. It examines the complex interactions of these bacteria with sialoglycan sugars on host cells and proteins, and how these events are affected by the high flow conditions within the heart. This research will provide important scientific insights about how endocarditis is produced, and may lead to novel therapies.

PI_NAMEs: LOPEZ, JOSE ARON;SULLAM, PAUL M.;THOMAS, WENDY E (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Address;adhesion receptor;Affect;Affinity;Animal Model;antigen binding;Antigens;Attenuated;Bacteria;Bacterial Adhesins;Binding;Binding Proteins;Biomechanics;Biomedical Engineering;Blood;Blood Cells;Blood Circulation;Blood Platelets;Cardiac;Cell Wall;Cells;Circulation;Coagulation Process;Collagen;Complex;Disease;disease model;Disease Progression;Endocarditis;Endocardium;Endothelium;enhancing factor;Event;Family;Fibrin;Flow Cytometry;Genes;Glycoproteins;healing;Heart;heart damage;Heart Valves;hemodynamics;Human;Immobilization;In Vitro;in vivo;Infection;Infective endocarditis;insight;lactosamine;Lesion;Life;Ligands;Link;Measures;mechanotransduction;Mediating;Microbial Biofilms;Microfluidics;microorganism interaction;Modeling;Mutagenesis;mutant;new therapeutic target;novel;novel therapeutics;oral streptococci;Organism;pathogen;Pathogenesis;Pathogenicity;Physiological;Plasma;Plasma Proteins;Platelet Activation;platelet function;Polysaccharides;Production;Proteins;Rattus;receptor;recruit;Research;Role;Serine;shear stress;sialic acid binding Ig-like lectin;single-cell RNA sequencing;Site;Site-Directed Mutagenesis;Stream;Streptococcus;Streptococcus gordonii;Streptococcus sanguis;Structure;sugar;Surface;Thrombosis;Thrombus;Trisaccharides;Variant;Vascular Endothelial Cell;Virulence;Virulent;von Willebrand Factor;Work

PROJECT_TITLE: Role of sialoglycan binding in the pathogenesis of streptococcal endocarditis

STUDY_SECTION: BHI

STUDY_SECTION_NAME: Bacterial-Host Interactions Study Section [BHI]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: SAINT LOUIS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project narrative Mitochondria, commonly known as the “powerhouses of the cell,” facilitate much of the energy production in cells, but how they respond to dynamic cellular cues is not fully understood. This proposal will test the hypothesis that phosphorylation constitutes an important regulatory mechanism in mitochondria. As kinases, the mediators of phosphorylation, are clinically relevant therapeutic targets, this project may reveal new pharmacological strategies to address mitochondrial dysfunction in human disease.

PI_NAMEs: NIEMI, NATALIE  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: Address;Affect;Biochemical;Cells;Citric Acid Cycle;Clinical;clinically relevant;Complement;Complex;Cues;Data;Energy Metabolism;Eukaryotic Cell;Event;Functional disorder;Genetic Identity;Homeostasis;human disease;Human Pathology;Individual;Ions;Knock-out;Knockout Mice;Knowledge;Link;Maps;Mediating;Mediator;Metabolic;Metabolic dysfunction;Metabolism;Mitochondria;mitochondrial dysfunction;Mitochondrial Proteins;Modification;Mus;new therapeutic target;Nutrient;Organelles;Perinatal mortality demographics;pharmacologic;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Physiological;Play;Process;Production;protein function;Protein Import;Protein phosphatase;Proteins;Regulation;Reproducibility;Role;Testing;therapeutic target;virtual;Work

PROJECT_TITLE: Delineating phosphorylation-mediated regulation of mitochondrial function

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular

ORG_CITY: DURHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Defects in normal blood vessel function, or vascular homeostasis, are responsible for a variety of cardiovascular disorders that have a significant impact on public health, including atherosclerotic heart disease, cancer, high blood pressure, and septic shock, among others. This project focuses on a newly identified protein, Caskin2, that we have found to play an important role in regulating vascular homeostasis, at least in part through endothelial nitric oxide synthase (eNOS), a well-known regulator of blood vessel health. By determining Caskin2's mechanisms of action as well as its effects in models of different vascular diseases, these studies may ultimately lead to new treatments for numerous cardiovascular diseases that account for substantial death and suffering in the US and worldwide.

PI_NAMEs: KONTOS, CHRISTOPHER D (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Address;Adhesions;angiogenesis;Angiopoietins;ANGPT1 gene;Apolipoprotein E;atheroprotective;Atherosclerosis;Binding;Binding Sites;Biology;Blood Vessels;Calmodulin;Cardiovascular Diseases;cardiovascular disorder prevention;Cell Physiology;Cell Survival;Cessation of life;Co-Immunoprecipitations;Coronary heart disease;CRISPR/Cas technology;Defect;density;Endothelial Cells;endothelial dysfunction;Endothelium;Event;gain of function;Gene Expression;Genetic;Genetic Transcription;Goals;Health;Homeostasis;Hypertension;hypertensive;In Vitro;in vivo;induced pluripotent stem cell;Inflammation;Ligands;Link;Liquid substance;loss of function;Malignant Neoplasms;Mediating;Modeling;Molecular;monocyte;Mus;mutant;Myography;Nitric Oxide;NOS3 gene;novel;Oxygen;Pathologic Neovascularization;Perfusion;Permeability;Phenotype;Phosphorylation;Play;pressure;prevent;Proliferating;Proteins;Public Health;receptor;Receptor Signaling;Recombinant Proteins;Regulation;Regulatory Pathway;response;Retinal Diseases;rho;Role;Scaffolding Protein;Septic Shock;shear stress;Signal Pathway;Signal Transduction;Testing;transcription factor;Transcription Factor AP-1;Vascular Diseases;vascular inflammation;Vascular Permeabilities;Vascular remodeling;western diet

PROJECT_TITLE: Mechanisms Regulating Vascular Homeostasis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cannabinoid Research;Endocannabinoid System Research;Nutrition;Obesity

ORG_CITY: NEW YORK

ORG_DEPT: CHEMISTRY

ORG_NAME: CITY COLLEGE OF NEW YORK

ORG_STATE: NY

PHR: Animal studies have demonstrated that the regulation of food intake requires articulation among endogenous cannabinoids (ECs), fatty acid-binding proteins (FABPs), and a peroxisome proliferator- activated nuclear receptor (PPARa), but the macromolecular basis for appetite, satiety, and obesity is poorly understood. This project will probe the solution-state macromolecular structure and function of EC- FABP, EC-PPAR, and FABP-EC-PPAR complexes in vitro at near-physiological concentrations, determining affinities, metabolic fates, molecular binding interfaces, and conformational changes to test proposed mechanisms of EC metabolic signaling. Working as a team with research trainees, our work will help to understand health risks and design future therapies for heart disease, autoimmune disorders, and type-2 diabetes.

PI_NAMEs: STARK, RUTH E. (contact)

PROGRAM_OFFICER_NAME: PEI, WUHONG

PROJECT_TERMS: Abbreviations;Address;Affinity;Amides;Animal Model;Animals;Appetite Regulation;Applications Grants;Articulation;Autoimmune Diseases;Binding;Binding Proteins;Binding Sites;Biological Assay;Biophysics;career;Cell Nucleus;Chemicals;Chimera organism;Complex;design;Desire for food;Diffusion;Dissociation;Drug Design;Drug Modulation;endocannabinoid signaling;Endocannabinoids;Enterocytes;Enzymes;Esters;Exhibits;experimental study;fatty acid amide hydrolase;fatty acid-binding proteins;Fatty Acids;Fluorescence;Food Intake Regulation;Future;Genetic Transcription;Glycerol;Health;heart disease risk;Heart Diseases;Human;Hydrophobicity;In Vitro;in vitro testing;Inflammation;Intestines;Knock-out;Knockout Mice;Ligand Binding;Ligand Binding Domain;Ligands;Lipase;Liver;Measures;Mediating;member;Metabolic;Modeling;Molecular;Molecular Chaperones;Molecular Conformation;Molecular Structure;Monitor;Mus;neuroprotection;NMR Spectroscopy;Non-Insulin-Dependent Diabetes Mellitus;Nuclear Receptors;Obesity;Outcome;Pain;Pattern;Peroxisome Proliferator-Activated Receptors;Peroxisome Proliferators;Phenotype;Physiological;preference;pressure;programs;Protein Binding Domain;protein complex;protein protein interaction;Proteins;receptor binding;recruit;Regulation;Relaxation;Research;Risk;Role;Satiation;Signal Transduction;Signaling Molecule;Site;Surface Plasmon Resonance;Testing;Thermodynamics;Thinness;thyroid hormone receptor associated protein 220;Titrations;Underrepresented Populations;United States National Institutes of Health;Vertebral column;Work

PROJECT_TITLE: Molecular Drivers of FABP-mediated Endocannabinoid Signaling for Appetite Regulation


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Breast Cancer;Breastfeeding, Lactation and Breast Milk;Cancer;Nutrition;Women's Health Research

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that is expressed on normal breast cells, where it regulates the production of parathyroid hormone-related protein (PTHrP) and calcium transport during lactation in order to coordinate maternal calcium and bone metabolism with calcium demand for milk production. This project will study how heterodimerization of the CaSR with the metabotropic GabaB receptors, GABBR1 and GABBR2, affects the ability of the CaSR to regulate PTHrP production and calcium transport into milk. These studies will advance the understanding of how the CaSR and the GabaB receptors affect the normal breast and have the potential to discover new ways to target the CaSR therapeutically.

PI_NAMEs: WYSOLMERSKI, JOHN J (contact)

PROGRAM_OFFICER_NAME: WINER, KAREN

PROJECT_TERMS: 3-Dimensional;Adenylate Cyclase;Affect;Biology;Biosensor;bone metabolism;Bone Resorption Stimulation;Breast;Breast Cancer Cell;Breast Epithelial Cells;Calcium;calcium metabolism;Calcium-Sensing Receptors;cancer cell;Cell secretion;cell type;Cells;Cessation of life;Couples;Coupling;Cyclic AMP;Data;dimer;Event;extracellular;Feedback;Fluorescence Resonance Energy Transfer;Functional disorder;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;GABBR2 gene;gamma-Aminobutyric Acid;Gases;Gene Modified;GTP-Binding Proteins;Heterodimerization;In Vitro;in vivo;Ion Transport;Lactation;Malignant Breast Neoplasm;mammary;mammary epithelium;MCF10A cells;Mediating;member;Membrane;Milk;milk production;Mus;Nervous System;Neurotransmitters;novel;Organ;parathyroid hormone-related protein;Physiology;Production;Proliferating;protein function;Protein Secretion;receptor;receptor expression;receptor function;Receptor Signaling;Regulation;response;Signal Transduction;Skeleton;System;Techniques;Therapeutic;three dimensional cell culture;Time;Transfection;tumor growth;virtual

PROJECT_TITLE: Heterodimerization of the Calcium-sensing receptor with the GabaB receptors in the breast.

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


ADMINISTERING_IC: AR

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: PHILADELPHIA

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative The muscle community at the University of Pennsylvania has established an outstanding training program in Muscle Biology and Muscle Disease, supported in part by the T32 mechanism. Members of the Penn community are known world-wide for excellence in muscle research, and this program facilitates collaborative training opportunities for predoctoral students and postdoctoral fellows. Our training program enables trainees to work in laboratories directed by principal investigators who are leaders in the study of the cell biology, genetics, physiology, and/or pathology of muscle.

PI_NAMEs: OSTAP, E. MICHAEL (contact)

PROGRAM_OFFICER_NAME: VINCENT, ISAAH S

PROJECT_TERMS: Biology;Muscle;Myopathy;Training

PROJECT_TITLE: Training in Muscle Biology and Muscle Disease


ADMINISTERING_IC: TW

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prostate Cancer;Racial and Ethnic Minority Health Research;Urologic Diseases

ORG_CITY: KINGSTON

ORG_COUNTRY: JAMAICA

ORG_FIPS: JM

ORG_NAME: UNIVERSITY OF THE WEST INDIES

PHR: The lack of representation of samples from men of African ancestry (MAA) at preclinical and clinical research is believed to contribute to the higher incidence and mortality rates of prostate cancer among MAA. As cell lines are tools used to understand the biology of tumours from which they are derived as well as to develop theranostics, the under-representation of these need urgent rectifying. This project seeks to develop novel MAA cell lines that will aid in developing novel therapies from Jamaican natural products for MAA with PCa, a patient population with the highest incidence and worst mortality rates for PCa.

PI_NAMEs: BADAL, SIMONE ANNMARIE (contact)

PROGRAM_OFFICER_NAME: LEVINTOVA, MARYA

PROJECT_TERMS: Address;Advanced Development;Africa;African;African ancestry;American;Androgens;anti-cancer research;Benchmarking;Biological Assay;Biological Markers;Biology;black men;Blood;Cancer cell line;Cancer Etiology;cancer health disparity;Cancer Patient;Caribbean region;Caucasians;Cell Culture Techniques;Cell Death;cell immortalization;Cell Line;Cell model;Cells;Cessation of life;Chemotactic Factors;chemotherapy;Clinical Research;Clinical Trials;comparative;comparative efficacy;Country;cytokine;cytotoxicity;Death Rate;deprivation;Development;Diagnosis;Disease;Disparity;Drug Screening;DU145;efficacy evaluation;Enrollment;Enzyme-Linked Immunosorbent Assay;European ancestry;Exhibits;experience;experimental study;Failure;Flow Cytometry;formamide;Fox Chase Cancer Center;Future;Genotype;Goals;Grana;Growth;health disparity;Immunohistochemistry;Incidence;Invaded;Jamaica;Jamaican;Lead;LNCaP;Luminescent Measurements;Malignant neoplasm of prostate;Malignant Neoplasms;men;Mentors;Mentorship;Microscope;migration;Modeling;Molecular;Molecular Abnormality;Molecular Biology Techniques;Morphology;mortality;Natural Products;novel;novel therapeutics;Oncology;Outcome;patient population;Patients;PC3 cell line;Persons;Pharmaceutical Preparations;Population;pre-clinical;Pre-Clinical Model;pre-clinical research;prostate cancer cell;prostate cancer cell line;prostate cancer model;Protocols documentation;Reporting;Research;Research Personnel;Sampling;Serum;standard of care;Starvation;success;System;Testing;theranostics;Therapeutic;Therapeutic Agents;Tissues;tool;Training;tumor;Tumor Biology;Tumor Subtype;Universities;Vendor;Viral;Work

PROJECT_TITLE: Novel Prostate Cancer Cell Lines to Address Prostate Cancer Disparity in Black Men

STUDY_SECTION_NAME: International and Cooperative Projects - 1 Study Section[ICP1]


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

ORG_CITY: LA JOLLA

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative The misuse of both prescription and illegal opioids has led to a national crisis that affects public health and the economy. However, we have little understanding of the genes that contribute to prescription opioid use disorders. This application will combine a rodent model of oxycodone abuse with emerging genomics technologies to dissect the molecular mechanisms underlying the vulnerability to opioid addiction and to identify genes that can be targeted for novel therapeutics development.

PI_NAMEs: BENNER, CHRISTOPHER W;TELESE, FRANCESCA  (contact)

PROGRAM_OFFICER_NAME: LOSSIE, AMY C

PROJECT_TERMS: Abstinence;Acute;addiction;Address;Affect;American;Area;ATAC-seq;Atlases;Behavior;Behavioral;Behavioral Model;behavioral phenotyping;behavioral study;Binding;Biochemical Pathway;Brain;Brain region;brain tissue;Cell Nucleus;cell type;Chromatin;cohort;Communicable Diseases;Complex;Computer Analysis;Computing Methodologies;Data;deep sequencing;Dependence;Development;Disease;Drug abuse;Drug Kinetics;Drug Prescriptions;Drug usage;Enhancers;Epigenetic Process;epigenomic profiling;epigenomics;Exhibits;Exposure to;Female;Gene Expression;Gene Expression Regulation;gene network;gene regulatory network;Gene Targeting;Genes;Genetic;genetic approach;Genetic Enhancer Element;Genetic Transcription;genetic variant;Genome;genome wide association study;genome-wide;genome-wide analysis;genomic data;genomic profiling;Genomic Segment;Genomics;Goals;Hepatitis;Heritability;Heroin;Hi-C;HIV;Human;Human Genetics;human study;Illicit Drugs;Inbred Strain;Inbred Strains Rats;innovation;Intake;Intoxication;male;Maps;Methods;Modeling;Molecular;Motivation;Neonatal Abstinence Syndrome;new therapeutic target;novel;Nucleotides;Opiate Addiction;Opioid;opioid epidemic;opioid use disorder;Overdose;Oxycodone;oxycodone seeking;oxycodone self-administration;Pain;Phenotype;prescription opioid;prescription pain reliever;prolonged abstinence;Protocols documentation;Public Health;Rat Strains;Rattus;Regulation;Regulator Genes;Regulatory Element;Resolution;response;Risk;RNA;Rodent Model;Role;Sampling;Scientist;screening;sex;Small RNA;Techniques;Technology;therapeutic development;Time;Tissues;trait;Transcript;transcription factor;Transcription Initiation;Transcription Initiation Site;transcription regulatory network;Transcriptional Regulation;transcriptome sequencing;Translating;United States;Untranslated RNA;Variant;Ventilatory Depression

PROJECT_TITLE: Decoding the grammar of transcriptional enhancers regulating different stages of opioid use disorder


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

ORG_CITY: COLLEGE PARK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: Project Narrative – Overall Component Influenza is a major problem worldwide, and despite decades of research, many questions remain about the factors that affect transmission, particularly how various routes of infection contribute to transmission and disease severity. This U19 Project addresses a critical need to improve the understanding of influenza transmission in humans. To this end, our consortium of world-renowned virologists, immunologists, epidemiologists, aerosol scientists, computational fluid dynamic modelers, aerobiologists, and engineers is developing and applying state-of-the-art methods to examine transmission including the use of an experimental human transmission study and analytical models of bioaerosols.

PI_NAMEs: MILTON, DONALD KIRBY (contact)

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TERMS: Acute;Address;Adult;aerosolized;Aerosols;Affect;Air;analytical method;analytical tool;Animals;Antibodies;Biological Assay;Biomedical Engineering;Biostatistics Core;Breathing;Cell Line;Clinical;clinical infrastructure;Clinical Research;Clinical Trials;Collection;Communication;Community-Acquired Infections;Complex;Controlled Environment;Data;density;design;Development;Devices;digital;Disease;Engineering;Environment;environmental intervention;Environmental Risk Factor;Epidemiologist;Exhalation;Face;Ferrets;Fever;flu transmission;Fractionation;Frequencies;Goals;Growth;Hand;Hemagglutination;Household;Human;Hydrogels;Hygiene;Immunologist;Immunology;improved;Individual;indoor air;indoor exposure;Infection;Infection Control;Infectious Disease Epidemiology;Influenza;influenza infection;influenzavirus;Inhalation;inhibiting antibody;innovation;innovative technologies;insight;instrument;Intervention;Knowledge;Liquid substance;Measurable;Measurement;Methods;Modeling;Molds;Monitor;Mucous body substance;multidisciplinary;National Institute of Allergy and Infectious Disease;Natural History;new technology;novel;Participant;particle;Particle Size;Pathogenesis;Patients;Performance;Physical condensation;Positioning Attribute;Predisposition;Public Health;quantum;Quarantine;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Research;research facility;Research Personnel;Research Project Grants;Research Support;Resources;Risk Assessment;Role;Route;Running;Sampling;Sanitation;Science;Scientist;seasonal influenza;Serology;Severity of illness;Solid;Strategic Planning;Symptoms;System;Technology;technology development;Testing;therapy design;timeline;tool;Translating;transmission process;trial design;universal influenza vaccine;ventilation;Viral;viral transmission;Virion;virology;Virus;Virus Shedding;volunteer;Water

PROJECT_TITLE: Evaluating Modes of Influenza Transmission (EMIT-2) using Innovative Technologies and Designs in Controlled Environments


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Infectious Diseases;Influenza;Pneumonia and Influenza

PROJECT_TERMS: Accountability;Achievement;Address;aerosolized;Aerosols;Air;Applications Grants;Area;Biological Assay;Biomedical Engineering;Biostatistics Core;Clinical;Clinical Research;Clinical Trials;Collaborations;Communication;Controlled Environment;design;Development;Devices;Disparity;Educational Status;Ensure;Environmental Risk Factor;Evaluation Research;Faculty;flu transmission;Fostering;Fractionation;Goals;Human;Immunology;improved;Individual;Infectious Disease Epidemiology;Influenza;influenzavirus;Information Dissemination;innovation;innovative technologies;Interdisciplinary Study;Knowledge;Language;Leadership;Liquid substance;meetings;Methods;Modeling;multidisciplinary;new technology;particle;Process;program dissemination;programs;Publications;Randomized, Controlled Trials;Report (document);Research;Research Personnel;Research Project Grants;Research Support;Resources;response;Role;Sampling;Science;sound;Standardization;Structure;Students;success;Sum;synergism;Technology;Viral;virology;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Clinical Research;Dissemination and Implementation Research;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Sexually Transmitted Infections;Social Determinants of Health;Women's Health Research

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE This study aims to decrease the burden of syphilis on vulnerable populations through implementation of an emergency department screening program that can be deployed in high-risk communities. This will have a huge potential impact on public health by decreasing complications of syphilis, interrupting the cycle of disease transmission and decreasing congenital syphilis. This work addresses NIH priorities to utilize implementation science to evaluate evidence-based practices for dissemination and implementation in real-world settings, as well as NIAID goals to develop innovative strategies to end the global epidemic of sexually transmitted infections.

PI_NAMEs: STANFORD, KIMBERLY  (contact)

PROGRAM_OFFICER_NAME: CHUANG, ELEANORE JENNIFER

PROJECT_TERMS: Accident and Emergency department;Address;Adopted;Adoption;Adult;Affect;aged;Ambulatory Care;American;Area;black patient;Black race;burden of illness;Cardiovascular system;career development;Caring;Case Study;Characteristics;Chicago;child bearing;Clinic;Clinic Visits;Clinical;Clinical Investigator;Communicable Diseases;Communities;Congenital Abnormality;Congenital Syphilis;contextual factors;cost;Cost Analysis;Country;Data;Detection;Diagnosis;Disease;disease transmission;Dissemination and Implementation;economic evaluation;economic implication;Emergency department screening;Epidemic;Epidemiology;ethnoracial disparity;Evaluation;Evidence based practice;experience;Exploration, Preparation, Implementation, and Sustainment;Failure;Feasibility Studies;Female of child bearing age;Financial Hardship;follow-up;Foundations;Future;Goals;health care economics;Healthcare Systems;high risk;hispanic community;Hospitals;implementation barriers;implementation outcomes;implementation science;implementation strategy;improved;Incidence;Individual;infant infection;Infection;infection risk;innovation;Institution;Interruption;Interview;Knowledge;Lead;Left;Location;Medical;meetings;member;men who have sex with men;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methodology;Methods;Minority Groups;Modeling;Mothers;National Institute of Allergy and Infectious Disease;Neurologic;obstetric care;Outcome;Patients;Persons;Phase;pilot test;Population Heterogeneity;Population Surveillance;Pregnant Women;Preparation;Prevention;Primary Care;Primary Prevention;programs;Provider;Public Health;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Readiness;Reporting;reproductive;Research;Research Methodology;Research Personnel;Risk;Risk Factors;routine care;scale up;screening;screening program;Services;Sexually Transmitted Diseases;Site;skills;Source;stillbirth;success;surveillance data;Symptoms;Syphilis;Syphilis Serodiagnosis;System;Testing;Time;Training;United States National Institutes of Health;uptake;Vulnerable Populations;Woman;Work;young woman

PROJECT_TITLE: Implementation of emergency department screening to impact rising syphilis rates in vulnerable populations

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Patient Safety;Pneumonia and Influenza;Prevention;Vaccine Related

PI_NAMEs: CHEN, WILBUR H. (contact)

PROJECT_TERMS: Acclimatization;Acute;Address;Admission activity;Adult;Aerosols;Baltimore;Biostatistics Core;care seeking;Clinical;clinical infrastructure;Clinical Investigator;Clinical Research;Clinical Trials;Clinical Trials Data Monitoring Committees;cohort;Collaborations;Collection;Consent;Containment;Controlled Environment;design;Eligibility Determination;Enrollment;Ensure;environmental intervention;Environmental Risk Factor;Event;Exhalation;experience;experimental study;Exposure to;flu transmission;Goals;Good Clinical Practice;Health;Hemagglutination;high risk;Human;Human Resources;Human Subject Research;Human Volunteers;Immunosuppression;indexing;Individual;Infection;infection risk;Influenza;influenza infection;influenza virus strain;influenza virus vaccine;Informed Consent;Infrastructure;inhibiting antibody;innovative technologies;Inpatients;Institutional Review Boards;Intervention;Laboratories;Maryland;Masks;Mediating;Medical;men;Methods;Molecular Diagnostic Testing;National Institute of Allergy and Infectious Disease;Outcome;Participant;Patients;Population Heterogeneity;Predisposition;Procedures;Process;programs;Protocols documentation;public health intervention;Quality Control;Randomized;Randomized, Controlled Trials;Recording of previous events;recruit;Research;research facility;Research Personnel;Research Project Grants;respiratory virus;Risk Reduction;Safety;Sampling;Screening procedure;seasonal influenza;Seasons;Series;Serology;Site;Specific qualifier value;Standardization;Symptoms;Technology;therapy design;Time;Training;transmission process;Universities;vaccine development;Vaccines;Viral;volunteer;ward;Woman

PROJECT_TITLE: Clinical and Biostatistics Core


NIH_SPENDING_CATS: Hematology

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Narrative Controlling platelet levels is central to management of various pathologies. Platelets develop from megakaryocytes in a bone marrow environment, the stiffness of which varies, with potential to generate mechanical constraints. Here, we propose an integrative approach to study specific megakaryocyte mechanobiological receptors, such as those termed Piezo proteins (called so from the Greek word for pressure), that sense the bone marrow matrix forces to control megakaryocyte adhesion and platelet biogenesis.

PI_NAMEs: RAVID, KATYA  (contact)

PROGRAM_OFFICER_NAME: GILLASPY, ALLISON

PROJECT_TERMS: Ablation;Actins;Address;Adhesions;Adult;Affect;Area;attenuation;Basement membrane;Biogenesis;Biology;Blood Platelets;blood product;Blood Vessels;Bone Marrow;Calcium;Cations;Cell Physiology;Cells;Collagen;Collagen Receptors;Collagen Type IV;crosslink;Cytoskeleton;Development;Environment;experimental study;Extracellular Matrix;Extracellular Matrix Proteins;Family;Fibronectin Receptors;Fibronectins;Generations;Genetic;Goals;Greek;Hemorrhage;Hemostatic function;high risk;Human;Image;In Vitro;in vivo;innovation;insight;Integrins;Intravenous Immunoglobulins;Investigation;Knock-out;Knockout Mice;Knowledge;leukemia;Life;Marrow;Measurement;Mechanics;Mechanoreceptors;mechanotransduction;Mediating;Megakaryocytes;member;mimetics;mouse model;Mus;Myelosuppression;Neurons;novel;Outcome;Pathology;Pathway interactions;Patients;pharmacologic;Phenotype;Piezo 1 ion channel;Piezo 2 ion channel;Platelet Count measurement;Platelet Transfusion;Play;Ploidies;preference;pressure;prevent;Production;Property;Proteins;receptor;Receptor Activation;Reporting;Research;Research Proposals;response;Role;side effect;Signal Transduction;Structure;Testing;Thrombocytopenia;thrombocytosis;Thrombopoietin;Thrombosis;thrombotic;transcription factor;Transfusion;translational potential;Tubulin;Visualization

PROJECT_TITLE: Megakaryocyte Mechanosensing Toward Platelet Biogenesis

STUDY_SECTION: HTBT

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


ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROGRAM NARRATIVE Achieving long-term survival of organ transplants without the need for chronic immunosuppression will provide transplant recipients with a healthier and longer life. These studies will explore ways to eliminate the need for chronic immunosuppressive drugs in patients undergoing heart transplantation.

PI_NAMEs: MADSEN, JOREN C (contact)

PROGRAM_OFFICER_NAME: SCHWARTZ, LISA

PROJECT_TERMS: Allograft Tolerance;Allografting;Antibody-drug conjugates;BCL2 gene;Bone Marrow Transplantation;Chest;Chimerism;Chronic;Clinical;clinical application;clinical trial readiness;clinically relevant;conditioning;cytokine;design;effector T cell;Engraftment;Ethics;Exhibits;FRAP1 gene;Funding;Goals;Heart;heart allograft;Heart Transplantation;Hematopoietic;High Density Lipoproteins;Homeostasis;Human;Immune;Immune response;Immunity;Immunosuppression;Immunosuppressive Agents;improved;Innate Immune Response;innovation;insight;Interleukin-2;islet;Kidney;kidney allograft;Kidney Transplantation;Laboratories;Life;Liver;liver allograft;Lung;lung allograft;Lung Transplantation;Macaca fascicularis;Macrophage;Modeling;nanotherapy;next generation;nonhuman primate;novel;novel strategies;Organ;Organ Survival;Organ Transplantation;Pathway interactions;Patients;programs;Protocols documentation;Radiation;Regimen;Regulatory T-Lymphocyte;Resistance;Seminal;Signal Transduction;stem cells;T memory cell;Time;TNFSF4 gene;Toxic effect;Training;Transplant Recipients;Transplantation;trial readiness;Vascularization;Work

PROJECT_TITLE: New Approaches to Inducing Cardiac Allograft Tolerance

STUDY_SECTION: HLBP

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP(MA)]


PROJECT_TERMS: Advisory Committees;Allograft Tolerance;animal data;Bibliography;Biometry;Communication;Consultations;Data Analyses;data exchange;design;Floor;Funding;Goals;heart allograft;Hospitals;Human Resources;Institution;Joints;Manuscripts;meetings;novel strategies;Preparation;professor;programs;Progress Reports;Publications;Reporting;Research;Research Design;Research Personnel;Resources;Sample Size;Structure;symposium;United States National Institutes of Health;Work

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Infectious Diseases;Influenza;Pneumonia and Influenza

PI_NAMEs: DEVOE, DON L (contact)

PROJECT_TERMS: Address;Aerosols;ambient particle;Biocompatible Materials;Biological Assay;Biomedical Engineering;Cell Culture Techniques;Cell Line;Clinical;Clinical Research;Collection;Controlled Environment;Coupled;density;design;Development;Devices;digital;Engineering;Environment;Evaluation;Exhalation;Exhibits;Ferrets;flu transmission;Fractionation;Gelatin;Goals;Growth;Heterogeneity;Human;Hydrogels;improved;Individual;Influenza;influenzavirus;innovation;innovative technologies;instrument;Investigation;Liquid substance;Lung;Methods;Microfluidics;model development;Modeling;Monitor;Mucins;Mucous body substance;novel;pandemic potential;particle;Particle Size;Physical condensation;Population;prevent;Property;Research;Research Project Grants;Resolution;respiratory;Respiratory System;Reverse Transcriptase Polymerase Chain Reaction;Risk;Risk Assessment;Route;sample collection;Sampling;Solid;Source;Support System;Surface;System;Techniques;Technology;tool;transmission process;Variant;Viral;viral pandemic;Virion;virology;Virus;water channel

PROJECT_TITLE: Advanced Bioaerosols Technology Core


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: TEMPE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Our knowledge of the full spectrum of genomic variation remains limited; this is particularly true of structural variation, which plays a highly important role in evolution, health, and disease. This proposed research will investigate the causes and consequences of structural variation focusing on three biomedically-relevant primate models. In addition to shedding new light onto disease pathogenesis, genome-wide comparisons across species will also provide novel insights into primate evolution.

PI_NAMEs: PFEIFER, SUSANNE P (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Behavioral Research;Biology;Biomedical Research;Catalogs;clinical phenotype;Code;Complex;Computing Methodologies;Data Set;Development;Disease;Etiology;Evolution;Frequencies;Gene Expression;Genes;Genetic Drift;Genetic Processes;Genetic Recombination;Genetic Variation;Genome;genome-wide;genomic data;genomic variation;Genomics;Health;Heart;Heritability;Historical Demography;Human;improved;insight;Knowledge;Length;Modeling;Molecular;Mutation;Natural Selections;neglect;nonhuman primate;novel;Nucleotides;Pathogenesis;Pattern;Phenotype;Play;Point Mutation;Population;Population Genetics;Primates;Process;Proteins;Research;Resolution;Role;Sampling;Shapes;single molecule;Source;Structure;Technology;Variant;Work

PROJECT_TITLE: Characterizing the full spectrum of genomic variation in biomedically-relevant primates

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


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: Project Narrative  Mobile genetic elements (transposons) are ubiquitous genetic elements capable of changing their physical location within the host DNA, thereby causing DNA damage and mutations, and interfering with the host genetic program. Animals have developed various defense strategies against transposons, including a sophisticated pathway that inhibits transposons in germ cells – the piRNA pathway, yet some tissues and developmental stages such as the early embryo appear to be relatively permissive to transposon activity. This proposal outlines a research program that aims to dissect the molecular mechanism of the piRNA pathway in germ cells and investigate the patterns and functional implications of transposon activity during development.

PI_NAMEs: NINOVA, MARIA ANTONINOVA (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Address;Animals;Area;Binding Sites;Biogenesis;Biology;Characteristics;Development;DNA;DNA Damage;DNA Sequence Alteration;DNA Transposable Elements;Drosophila genus;Elements;Embryo;Embryonic Development;Epigenetic Process;epigenetic variation;Evolution;Fertility;gene repression;Generations;Genetic;genetic element;genetic information;Genetic Transcription;Genetic Variation;Genome;Genomics;Germ Cells;Germ Lines;Goals;Human Genome;innovation;interest;Invertebrates;Laboratories;Left;Life;Literature;Location;Mediating;Mobile Genetic Elements;Modeling;Molecular;mouse genome;Mus;Nucleic Acid Regulatory Sequences;Organism;Pathway interactions;Pattern;permissiveness;piRNA;Play;posttranscriptional;preservation;Prevalence;prevent;programs;Proteins;Regulation;Research;Role;single cell sequencing;Somatic Cell;Source;Sumoylation Pathway;System;Technology;Tissues;Transcriptional Silencer Elements;transcriptome;Trees;Vertebrates

PROJECT_TITLE: Investigating the Molecular Basis of Transposon Regulation and Function in Animal Development

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CDB-L(55)R]


PI_NAMEs: BENICHOU, GILLES A (contact)

PROJECT_TERMS: Affect;Allograft Tolerance;Allografting;Antigens;Automobile Driving;Biological Assay;Biological Markers;Blood;Cells;Chimerism;Clinical;Clinical Trials;clinically relevant;design;Diagnosis;Dual-role transvestism;exosome;extracellular vesicles;Future;Generations;Genes;Goals;Heart;heart allograft;Heart Transplantation;Hematopoietic;Human;Immune response;immunogenic;immunoregulation;improved;in vivo;isoimmunity;Kidney;kidney allograft;Leukocytes;Maintenance;Mediating;Monkeys;Mus;Nature;nonhuman primate;novel strategies;Pathogenicity;Patients;Phenotype;Play;Procedures;programs;Protocols documentation;Recovery;Regulation;Regulatory T-Lymphocyte;Role;Serum;Specificity;T memory cell;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Translating;translation to humans;Transplant Recipients;Transplantation;Transplantation Tolerance;vesicular release;Work

PROJECT_TITLE: Core A: Elucidating the Mechanisms Underlying Mixed-Chimerism Based Tolerance


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention

PROJECT_TERMS: Address;Adult;Aerosols;Air;air sampling/monitoring;Antibodies;Biomedical Engineering;Biostatistics Core;Carbon Dioxide;Clinical;Collaborations;Community-Acquired Infections;Controlled Environment;Data;design;Disease;Drops;efficacy evaluation;Ensure;Environment;Exhalation;experience;experimental study;Exposure to;Face;Fever;flu transmission;Frequencies;Germicide;Goals;Hand;Hemagglutination;Human;Hygiene;Immune response;improved;Infection;Influenza;Influenza A Virus, H3N2 Subtype;influenza infection;Infrastructure;inhibiting antibody;innovative technologies;insight;instrument;instrumentation;Intervention;Knowledge;Maryland;Measurable;Measurement;Measures;Methods;Monitor;Mucous Membrane;multidisciplinary;National Institute of Allergy and Infectious Disease;Natural History;Neutralization Tests;Nonpharmacologic Therapy;novel;Participant;Pathogenesis;Positioning Attribute;Predisposition;prevent;Quarantine;Randomized;Randomized, Controlled Trials;recruit;Research;Research Design;Research Project Grants;Role;Route;Sanitation;Serology;Severity of illness;Strategic Planning;System;Technology;Testing;Therapeutic;transmission process;universal influenza vaccine;universal vaccine;Universities;vaccine efficacy;ventilation;Viral;Virus

PROJECT_TITLE: Evaluating Modes of Influenza Transmission using a Randomized Controlled Trial (EMIT-2-RCT)


PROJECT_TERMS: Allograft Tolerance;Allografting;Bone Marrow Transplantation;Cell Differentiation process;Cell Physiology;Chimerism;Chronic;clinical trial readiness;Combination immunotherapy;conditioning;Data;Development;FRAP1 gene;Funding;Goals;Graft Survival;Heart;heart allograft;Hematopoietic;High Density Lipoproteins;Histocompatibility Antigens Class I;Human;Immune;immune activation;Immune Tolerance;Immunity;Immunologic Memory;Immunosuppression;Inflammation;inhibitor;Interleukin-2;Kidney;kidney allograft;Laboratories;Liver;Lung;Macaca fascicularis;Macrophage;Molecular;Morbidity - disease rate;mortality;mTOR Inhibitor;mTOR protein;mutant;Myeloid Cells;nanobiologic;Nanoimmunotherapy;nanotherapy;next generation;nonhuman primate;novel;novel strategies;Organ;Organ Transplantation;Pathway interactions;Phase I Clinical Trials;Phase II Clinical Trials;platelet protein P47;prevent;Protocols documentation;Regimen;Regulatory T-Lymphocyte;Resistance;Sirolimus;T memory cell;Testing;Time;Training;Transplantation;treatment strategy;ubiquitin-protein ligase

PROJECT_TITLE: Project 1: Augmenting Regulatory Mechanisms in Protocols of Transient Mixed Chimerism


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_DEPT: NEUROSCIENCES

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

PHR: PROJECT NARRATIVE Small vessel disease (SVD) is a major public health threat to our aging population. It is a significant contributor towards Alzheimer’s dementia. Understanding SVD in the context of neurodegeneration will have broad implications for disease mechanisms, development of biomarkers, and diagnosis and prevention of SVD.

PI_NAMEs: KAPASI, ALIFIYA  (contact)

PROGRAM_OFFICER_NAME: ROVESCALLI, ALESSANDRA C

PROJECT_TERMS: Affect;African American;African American population;Age;Aging;aging population;Alzheimer's Disease;Alzheimer's disease pathology;Amyloid beta-Protein;Area;Arterioloscleroses;Autopsy;Biological Markers;Biological Process;biomarker development;Biometry;Blood Vessels;Brain;Brain region;brain tissue;brain volume;burden of illness;career;Cerebral Amyloid Angiopathy;cerebral atrophy;Cerebral small vessel disease;clinical translation;Cognition;Cognitive;Communities;comorbidity;Complex;Data;Dementia;dementia risk;Diagnosis;digital;digital pathology;Disease;Disease Marker;epidemiology study;Etiology;experience;Goals;health disparity;Hemorrhage;high risk;hippocampal atrophy;Hippocampus;Histopathology;Impaired cognition;in vivo;Inflammation;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Measures;Memory;Mentorship;Methods;Microglia;Microvascular Dysfunction;Minority;Nerve Degeneration;neuroimaging;neuropathology;novel;novel strategies;older adult;Older Population;Pathology;Persons;Postmortem Changes;Predisposition;Prevention;Public Health;religious order study;Research;Research Methodology;research study;Resources;Role;tau Proteins;Testing;tissue injury;Training;Translational Research;White Matter Hyperintensity;Work

PROJECT_TITLE: Small vessel disease contributions to neurodegeneration in Alzheimer's disease

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Heart Disease;Organ Transplantation;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

PI_NAMEs: KEAN, LESLIE S (contact)

PROJECT_TERMS: Address;allograft rejection;Allograft Tolerance;Allografting;Antibodies;Antibody-drug conjugates;Bone Marrow Stem Cell;cancer risk;Cells;Chest;Chimerism;Chronic;Clinic;Clinical;clinical translation;conditioning;Data;Defect;design;Development;Engraftment;genotoxicity;Goals;graft vs host disease;Half-Life;Heart;heart allograft;Heart Diseases;Heart Transplantation;Hematopoietic;Hematopoietic Stem Cell subsets;high risk;Homeostasis;Human;Immune Tolerance;Immunity;immunomodulatory strategy;immunoregulation;Immunosuppression;improved;innovation;irradiation;Kidney;Lung;lung allograft;Lung Transplantation;Lymphoproliferative Disorders;Marrow;Methods;Morbidity - disease rate;mortality;mTOR inhibition;Mus;Mutation;next generation;nonhuman primate;novel;novel strategies;Organ;Patient risk;Patients;post-transplant;preservation;prevent;Proto-Oncogene Protein c-kit;Protocols documentation;PTPRC gene;Regimen;Regulatory T-Lymphocyte;Risk;Rosaniline Dyes;Safety;Sirolimus;stem cell engraftment;Stem cell transplant;stem cells;success;Testing;Therapeutic;TNFSF4 gene;Toxic effect;Translating;Translations;Transplant Recipients;Transplantation Tolerance

PROJECT_TITLE: Project 2: Next-Generation Mixed Chimerism Induction for Heart Allograft Tolerance


NIH_SPENDING_CATS: Biotechnology;Childhood Obesity;Genetics;Human Genome;Neurosciences;Nutrition;Obesity;Pediatric;Prevention;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: NARRATIVE Our genome wide association studies (GWAS) of childhood obesity have revealed key loci influencing risk for the trait, with the data increasingly pointing to central nervous system processes. However, at the individual locus level, GWAS only reports genomic signals associated with a given trait and not necessarily the precise localization of culprit effector genes. Given the need for `variant to gene mapping', we will utilize `3D Genomic' and CRISPR based screens in iPSC-derived neuronal cell types to pinpoint the causal gene(s) at each key childhood obesity GWAS-implicated locus.

PI_NAMEs: GRANT, STRUAN F A (contact)

PROGRAM_OFFICER_NAME: CLARK, DAVID

PROJECT_TERMS: 3-Dimensional;Adult;Affect;Applications Grants;Astrocytes;ATAC-seq;Body mass index;Brain;causal variant;Cell model;cell type;Cells;Central Nervous System;Child;Child health care;Chromatin;chromosome conformation capture;Chromosome Mapping;Clustered Regularly Interspaced Short Palindromic Repeats;Communities;CRISPR screen;CRISPR/Cas technology;Data;Data Set;Dedications;Enhancers;Environmental Exposure;Ethnic Origin;Etiology;functional genomics;Funding;Gene Expression;Gene Targeting;Genes;Genetic;genome wide association study;genome-wide;genomic data;Genomics;Goals;Human;Hypothalamic structure;Individual;Induced pluripotent stem cell derived human neuron;Induced pluripotent stem cell derived neurons;Infrastructure;Life;lipid biosynthesis;Measures;Microglia;Mining;National Institute of Child Health and Human Development;Nature;nerve stem cell;Neurons;novel;Obesity;obesity in children;Pediatric Hospitals;Philadelphia;Principal Investigator;Process;promoter;Public Domains;Publishing;Reporting;Research;Research Design;Resolution;Risk;Series;Signal Transduction;trait;transcriptome sequencing;Translating;Variant;Waist-Hip Ratio

PROJECT_TITLE: Genome Wide Association Study for Childhood Obesity

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Influenza;Pneumonia and Influenza

PI_NAMEs: SREBRIC, JELENA  (contact)

PROJECT_TERMS: Accounting;Address;aerosolized;Aerosols;Air;Air Movements;analytical tool;Biological Assay;Biostatistics Core;Breathing;Carbon Dioxide;Chest;Clinical;cohort;Cohort Studies;Collection;Controlled Environment;Core Facility;Coupled;Data;data collection site;Data Set;Deposition;design;Development;Diameter;Disinfection;Dose;Environment;Environmental Monitoring;Equation;Exhalation;Experimental Designs;experimental study;Exposure to;Face;Ferrets;field study;flu transmission;Formulation;Generations;Germicide;Household;Human;human subject;Humidity;Indoor environment;infection rate;Influenza;influenzavirus;innovative technologies;Intervention;Investigation;Knowledge;Link;Liquid substance;Location;Measurable;Measurement;Measures;meter;Modeling;Nasopharynx;Nature;novel;Participant;particle;Particle Size;Positioning Attribute;Predictive Analytics;Prevention;Process;Public Health;Randomized, Controlled Trials;Research Project Grants;Risk;Risk Assessment;Route;Sampling;Sanitation;Scientist;Shapes;Source;Spatial Distribution;submicron;Technology;Temperature;Testing;therapy design;Time;tool;Translating;Translations;transmission process;user-friendly;Validation;ventilation;Viral;viral transmission;Virus;Virus Integration;Virus Shedding;web-based tool;Work

PROJECT_TITLE: Developing and Applying Analytical Models of Influenza Transmission


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Kidney Disease;Osteoporosis;Precision Medicine

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Treatment of renal osteodystrophy is impeded by the lack of practical and accurate tools to determine underlying bone turnover. Gold standard bone biopsy is not practical in the clinic for the vast majority of kidney disease patients and parathyroid hormone and bone alkaline phosphatase have insufficient accuracy for turnover type to safely and confidently guide treatment of renal osteodystrophy. In the present investigation, we will study a microRNA approach as a novel non-invasive biomarker of turnover for renal osteodystrophy.

PI_NAMEs: ALLEN, MATTHEW R;MOE, SHARON M;NICKOLAS, THOMAS L. (contact)

PROGRAM_OFFICER_NAME: CHAN, KEVIN E

PROJECT_TERMS: Affect;Aftercare;Alkaline Phosphatase;Area Under Curve;Biochemical Markers;Biological Markers;biomarker identification;biomarker panel;Biomechanics;Biopsy;Blood;bone;bone loss;bone quality;bone strength;Bone Tissue;bone turnover;Cardiovascular system;Cessation of life;Chronic Kidney Failure;circulating microRNA;Circulation;Clinic;Clinical;Clinical Trials;cohort;Complex;cortical bone;Data;Development;diagnostic accuracy;Dialysis patients;Discrimination;Disease;Disease Marker;Event;Failure;Fracture;Future;Goals;Guidelines;Histology;Hormones;Hyperparathyroidism;Impairment;improved;Incidence;Individual;Investigation;Kidney;Kidney Diseases;Kidney Failure;Label;long bone;Measures;Mechanics;microRNA biomarkers;MicroRNAs;Minerals;miRNA expression profiling;nanoindentation;nanomechanics;non-invasive imaging;noninvasive diagnosis;novel;Osteoblasts;Osteoclasts;Outcome;Patients;Performance;Peripheral;Population;precision medicine;Property;prospective;PTH gene;Publications;Publishing;Race;Raman Spectrum Analysis;Recommendation;Renal Osteodystrophy;Resolution;Risk;sex;Site;Testing;Tetracyclines;tool;treatment response;Vitamin D;X-Ray Computed Tomography

PROJECT_TITLE: Precision medicine approaches to renal osteodystrophy

STUDY_SECTION: KNOD

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


NIH_SPENDING_CATS: Aging;Arthritis;Bioengineering;Biomedical Imaging;Chronic Pain;Clinical Research;Osteoarthritis;Pain Research;Prevention;Rehabilitation

ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Osteoarthritis (OA), a multifactorial disease and understanding the complex pathophysiology of joint degeneration, knee and hip joint interactions, and the impact of gait biomechanics, are all critical to determine the mechanistic basis of hip OA. In this proposal subjects will be recruited for a longitudinal study (covering 5-8 year follow up) from our existing cohort and we will use novel, fully automated and translational methods to measure MRI-based measures of cartilage degeneration and determine the role of gait biomechanics on disease progression.

PI_NAMEs: MAJUMDAR, SHARMILA  (contact);SOUZA, RICHARD BRIAN

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: 3-Dimensional;Acceleration;adduct;Adult;Affect;Age;American;automated segmentation;Bilateral;Biochemical;Biochemistry;Biological Markers;Biomechanics;bone;Cartilage;cartilage degradation;Cartilage Matrix;cohort;Collagen;Complex;Contralateral;Data;Data Analyses;Data Set;Degenerative Disorder;Degenerative polyarthritis;demographics;Development;disability;Disease;Disease Progression;disorder risk;Early Diagnosis;Etiology;Exhibits;femur head;Financial Hardship;follow-up;Functional disorder;functional outcomes;Gait;gait examination;Goals;Health;high risk;Hip Joint;Hip Osteoarthritis;Hip region structure;hip replacement arthroplasty;human old age (65+);Image;Individual;Injury;innovation;insight;Intervention;Ipsilateral;joint destruction;Joints;kinematics;Kinetics;Knee;Knee joint;Knee Osteoarthritis;knee replacement arthroplasty;Lesion;Life;Limb structure;Link;Longitudinal Studies;machine learning algorithm;Magnetic Resonance Imaging;Maps;Measures;Mediating;Mediation;Mediator;Methods;Modeling;Morphology;Motivation;multidimensional data;Multivariate Analysis;novel;obese person;older adult;Operative Surgical Procedures;Outcome Measure;Pain;Pain Measurement;Patient Outcomes Assessments;Patients;Pattern;Phenotype;Prevalence;Preventive;Preventive treatment;Principal Component Analysis;Procedures;Progress Reports;Proteoglycan;quantitative imaging;rate of change;recruit;Relaxation;Replacement Arthroplasty;Reporting;Role;Rotation;Severities;Shapes;skeletal;Structure;Subgroup;Techniques;Time;Tissues;Water;Work

PROJECT_TITLE: Structural, Biochemical and Functional Connectivity in Osteoarthritis using Quantitative Magnetic Resonance Imaging and Skeletal Biomechanics

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


NIH_SPENDING_CATS: Aging;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: LAWRENCE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF KANSAS LAWRENCE

ORG_STATE: KS

PHR: his research is a necessary first step into crafting interventions to improve the career outcomes of AAorB faculty. Increasing the diversity of the biomedical workforce is essential to addressing the stubborn and persistent challenges of racial and ethnic health disparities. This research, like the previous work by Ginther et al (2011), will be used to develop policies that will lead to a more diverse biomedical workforce.

PI_NAMEs: GINTHER, DONNA K. (contact)

PROGRAM_OFFICER_NAME: STAMM, JOYCE CHIN-CHIN NG

PROJECT_TERMS: Address;African American;Age;age difference;Association of American Medical Colleges;Award;Binding;biomedical scientist;Black race;career;Career Choice;Characteristics;Color;Communities;Data;data enclave;Data Set;Databases;Disadvantaged;Education;Engineering;ethnic difference;ethnic health disparity;Ethnic Origin;Faculty;Foundations;Funding;Gender;gender difference;graduate student;Grant;Hazard Models;Health Sciences;improved;Individual;Information Systems;Institution;instructor;Internet;Intervention;Link;Longevity;longitudinal dataset;Measures;medical schools;member;mid-career faculty;Outcome;Policies;Progress Reports;Publications;Publishing;Race;racial difference;racial health disparity;Reporter;Research;research faculty;Research Personnel;Research Project Grants;Science;Science, Technology, Engineering and Mathematics;Scientist;Secondary Schools;senior faculty;statistics;Students;success;Surveys;systemic barrier;undergraduate student;United States;United States National Institutes of Health;Universities;Woman;Work

PROJECT_TITLE: SCISIPBIO: Examining the Career Barriers Confronting African American or Black Biomedical Scientists


ORG_CITY: BOSTON

PI_NAMEs: PIERSON, RICHARD N (contact)

PROJECT_TERMS: Adopted;allograft rejection;Allograft Tolerance;Amanitins;Antibodies;Antibody Therapy;Antibody-drug conjugates;Apoptosis;B-Lymphocytes;BCL2 gene;Bone Marrow Transplantation;Cadaver;CD28 gene;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Chimerism;Chronic;Clinical;clinical application;clinical trial readiness;clinically relevant;conditioning;cost;Data;design;effector T cell;Engraftment;experience;Failure;FDA approved;Funding;Goals;Graft Survival;Heart;heart allograft;Heart Transplantation;Human;IL17 gene;Immune Tolerance;Immunosuppression;improved;Inflammatory;innovation;Interferon Type II;Interleukin-6;isoimmunity;Kidney;kidney allograft;Kidney Transplantation;Laboratories;Lymphocyte;Macaca fascicularis;Modeling;Molecular;Monoclonal Antibodies;Monoclonal Antibody Therapy;Morbidity - disease rate;Myelosuppression;novel;novel strategies;Organ Donor;Organ Transplantation;Pathogenicity;Pathway interactions;Peripheral;Pharmaceutical Preparations;Pilot Projects;preservation;programs;Proliferating;Protocols documentation;Radiation;Regimen;Regulatory T-Lymphocyte;Risk;success;T memory cell;T-Lymphocyte;Testing;Time;Toxic effect;Transplantation;Whole-Body Irradiation

PROJECT_TITLE: Project 3: Enhanced Costimulation Blockade to Achieve Clinically Relevant Heart Allograft Tolerance


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Brain Disorders;Cocaine;Drug Abuse (NIDA only);Neurosciences;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Dopamine plays a role in many processes ranging from movement and reward to the regulation of hormonal balance. This study will identify the site of D2- receptor dependent dendrodendritic dopamine transmission. Knowledge of how the activity of dopamine neurons is regulated by endogenous dopamine and the plasticity of this form of transmission will facilitate an understanding of the abuse liability of cocaine.

PI_NAMEs: WILLIAMS, JOHN T (contact)

PROGRAM_OFFICER_NAME: BERTON, OLIVIER

PROJECT_TERMS: abuse liability;Acute;addiction;Affect;Affinity;Agonist;Anatomy;Animals;antagonist;Area;Attention Deficit Disorder;Attention deficit hyperactivity disorder;Behavior;Brain;Central Nervous System;Cocaine;Confocal Microscopy;Dendrodendritic Synapse;desensitization;Detection;Disease;Dopamine;Dopamine Agonists;Dopamine D2 Receptor;Dopamine Receptor;dopamine system;dopaminergic neuron;Drug Addiction;drug of abuse;Endocytosis;Equilibrium;Event;experimental study;Extracellular Space;Future;G-Protein-Coupled Receptors;GABA-B Receptor;Goals;GTP-Binding Proteins;Health;hormone regulation;Immunohistochemistry;induced pluripotent stem cell;Kinetics;Knock-in;Knowledge;Label;Ligands;Link;Location;Mediating;Mental Depression;Midbrain structure;Movement;Mus;neurobiotin;Neurons;Noise;Parkinson Disease;Pattern;photolysis;Physiological;Physiological Processes;Play;Population Heterogeneity;postsynaptic;Potassium;Process;receptor;Receptor Activation;receptor function;Receptor Signaling;Regulation;Resolution;Rewards;Role;Schizophrenia;sensor;Signal Transduction;Site;Slice;Substantia nigra structure;Synapses;Synaptic Potentials;temporal measurement;Therapeutic;Time;Transgenic Organisms;transmission process;two photon microscopy;Ventral Tegmental Area;Viral;Work

PROJECT_TITLE: Cocaine: effects on single neurons


NIH_SPENDING_CATS: Aging;Clinical Research;Disability Research;Eye Disease and Disorders of Vision;Health Services

ORG_CITY: ANN ARBOR

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE There is a critical need for clinical and epidemiological research to address the growing epidemic of noncommunicable eye disease among older adults in India, where blindness and vision impairment are the number one cause of years lived with disability in later life. This proposal builds on a longstanding partnership between the University of Michigan and Aravind Eye Care System (AECS) in South India. This multifaceted research capacity building program will provide graduate training in epidemiology to faculty at AECS, develop a supportive research ecosystem, and result in a long-term sustainable training program that will make vital contributions to vision research and to addressing the large burden of blindness and vision- related disability among older adults in India and beyond.

PI_NAMEs: EHRLICH, JOSHUA ROBERT (contact)

PROJECT_TERMS: Address;Age;Aging;aging population;American;blind;Blindness;Capsicum;care systems;career;Clinical and Translational Science Awards;clinical epidemiology;Clinical Research;Collaborations;Dedications;Dementia;design;disability;Disease;Education;education research;Educational Status;Environment;Epidemic;epidemiology study;Eye;Eye diseases;Faculty;fall risk;Funding;Grant;Home;Hospitalization;India;Institution;Intervention;Knowledge;late life;Life Cycle Stages;Mental Depression;Mentors;Methods;Michigan;middle age;mortality;Needs Assessment;older adult;Population;population health;programs;Recording of previous events;Research;Research Personnel;Research Training;Risk Factors;Role;Sensory;skills;success;Surveys;Training;Training Activity;training opportunity;Training Programs;United States National Institutes of Health;Universities;Vision;Visual disability;Visual impairment;years lived with disability

PROJECT_TITLE: Building Non-Communicable Eye Disease Research Capacity in India

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-L(55)R]


ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: NARRATIVE The burden of cardiovascular disease (CVD) in the United States (US) is steadily increasing, in part due to the aging of the US population, increased prevalence of conditions such as diabetes, chronic kidney disease and the metabolic syndrome and the emergence of high-risk populations, i.e., racial/ethnic minorities such as African-Americans and Hispanics, and persons infected with HIV/AIDS. These increasing health needs underscore the importance of training basic scientists, clinical scientists and population scientists in an environment conducive to multidisciplinary team research in order to test more effective approaches to the prevention and treatment of hypertension and related vascular disease and other comorbidities. This Training Program addresses these goals, and is the only postdoctoral Training Program in the state of Alabama with a primary focus on hypertension and CVD.

PI_NAMEs: YOUNG, MARTIN E (contact)

PROGRAM_OFFICER_NAME: WOO, SEUNG KYOON

PROJECT_TERMS: Cardiovascular Diseases;Hypertension

PROJECT_TITLE: Mechanisms of Hypertension and Cardiovascular Diseases

STUDY_SECTION: NITM

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


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

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Impairment of goal-directed behavior (GDB), often labeled apathy, is the most common and disabling of the neuropsychiatric symptoms observed in behavioral variant frontotemporal degeneration (bvFTD). This study uses fMRI network analyses to investigate mechanisms in bvFTD by which degraded functional brain networks underlying GDB contribute to the syndrome of apathy. This type of study is necessary to develop more effective and targeted treatment for apathy.

PI_NAMEs: MASSIMO, LAUREN M (contact)

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: Acceleration;Address;Admission activity;Affect;Alzheimer's disease related dementia;Anatomy;Atrophic;Behavior;behavioral impairment;Behavioral Symptoms;behavioral variant frontotemporal dementia;Brain;Brain region;Characteristics;Clinical;clinical prognosis;Clinical Trials;Cognition;Cognitive;cognitive function;Complex;Degenerative Disorder;Dementia;Deterioration;Dimensions;disability;Disabling;Disease;effective therapy;Effectiveness;efficacious treatment;Foundations;frontotemporal degeneration;functional decline;Functional Magnetic Resonance Imaging;Future;Goals;Human;Image;Impaired cognition;Impairment;Individual;insight;Investigation;Label;Magnetic Resonance Imaging;Maps;Mediating;mortality risk;Motivation;Motor;motor disorder;Nerve Degeneration;neural;Neuroanatomy;Neurocognitive;neuropsychiatric symptom;novel;Nursing Homes;Pathway Analysis;patient prognosis;Patients;Pharmacological Treatment;Process;prognostic indicator;Quality of life;Research Design;Rest;Rewards;Role;segregation;Self Care;Source;Syndrome;targeted treatment;Time;Work

PROJECT_TITLE: Multidimensional Approaches to Understanding Consequences and Mechanisms of Apathy in Frontotemporal Degeneration

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ADMINISTERING_IC: DE

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

ORG_NAME: YALE UNIVERSITY

PHR: NARRATIVE The Yale Head and Neck SPORE is a team of clinical and laboratory researchers studying the problem of treatment resistance in head and neck cancer. Each of three projects brings a basic and clinical research leader together to study ways to overcome resistance to common therapies, such as cetuximab and cisplatin, as well as to find ways to make HPV-driven cancers more sensitive to immunotherapy. There are clinical trials to treat patients with HPV-negative and HPV-driven cancer before they go to surgery. The projects are supported by core facilities to provide administrative, pathology and statistical support, and there are funds to support new projects and new investigators.

PI_NAMEs: BURTNESS, BARBARA  (contact)

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: Address;Animals;apolipoprotein B mRNA editing enzyme;aurora kinase A;barrier to care;Basic Science;Bioinformatics;Biometry;Cancer Biology;Cancer Center;career;Cell Line;Cells;Cellular biology;Cessation of life;Cetuximab;checkpoint inhibition;Cisplatin;Clinic;Clinical;Clinical Research;Clinical Trials;Collaborations;Combined Modality Therapy;Communities;conventional therapy;Core Facility;Correlative Study;curative treatments;Data;demethylating therapy;demethylation;Development;Disease;DNA Damage;EGFR inhibition;Epidermal Growth Factor Receptor;ERBB3 gene;Family;Family member;Fostering;Foundations;Fox Chase Cancer Center;Functional impairment;Funding;Future;Generations;Genes;Genomics;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Head and neck structure;HPV negative;HPV-negative head and neck cancer;Human;Human Papillomavirus;Immune;Immune response;Immunology;Immunotherapy;improved;inhibitor;insight;Institution;Laboratories;Link;Malignant Neoplasms;Mediating;Mentors;Methodology;Modality;Modeling;Molecular Abnormality;Molecular Conformation;mortality;Mutation;new therapeutic target;next generation;North Carolina;novel;novel strategies;Operative Surgical Procedures;oral HPV-positive head and neck cancers;Outcome;overtreatment;Pain;Pathology;Patients;Pharmacodynamics;Pharmacology;polypeptide;programs;Proteins;Radiation;Radiobiology;Recurrence;Reproduction spores;Research;Research Personnel;Resistance;Resources;response;Role;Safety;Sampling;Scientist;Signal Transduction;Specimen;structural biology;System;targeted treatment;therapy resistant;TP53 gene;Training;Translational Research;translational scientist;Translations;treatment response;tumor;United States;Universities;Validation;virology;Yale Cancer Center

PROJECT_TITLE: Yale Head and Neck Cancer SPORE: Overcoming Treatment Resistance in Head and Neck Cancer


NIH_SPENDING_CATS: Data Science

ORG_CITY: KAMPALA

ORG_COUNTRY: UGANDA

ORG_FIPS: UG

ORG_NAME: MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES

PHR: PROJECT NARRATIVE Africa is facing a triple burden of disease i.e. a high incidence of fatal infectious diseases, non- communicable diseases, and emerging epidemics (with pandemic potential). Addressing these will require a new thinking and approaches for generating and synthesizing evidence that can inform policy. Research training in LICs provides an avenue to build capacity for locally generated investigations aimed at preventing and controlling these diseases. Leveraging on existing infrastructure at Makerere University College of Sciences and international collaboration with Johns Hopkins University, we propose a plan for a comprehensive multi-disciplinary data science research-training program in Uganda.

PI_NAMEs: CHECKLEY, WILLIAM ;JOLOBA, MOSES LUTAAKOME;KATEETE, DAVID PATRICK (contact)

PROGRAM_OFFICER_NAME: POVLICH, LAURA

PROJECT_TERMS: Accreditation;Africa;Award;career;Caring;Collaborations;Competence;Data Science;Doctor of Philosophy;Educational Curriculum;evidence base;Faculty;Fostering;Goals;Graduate Degree;Grant;Guidelines;Health;Health Sciences;innovation;International;Intervention;Investments;Joints;Knowledge;Maps;Measurable;Medicine;Mentors;Mentorship;Performance;Policies;post-doctoral training;Postdoctoral Fellow;programs;Publications;Research;Research Training;skills;Time;Training;Training Activity;Training and Infrastructure;Training Programs;Uganda;Universities

PROJECT_TITLE: Makerere University Data Science Research Training to Strengthen Evidence-Based Health Innovation, Intervention and Policy (MakDARTA)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-C(70)]


NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Lung;Lung Cancer;Rare Diseases

PHR: PROJECT NARRATIVE The Administration Core (Core A) is essential for leading the Yale Head and Neck SPORE (YHN-SPORE). The Core will provide scientific, financial and administrative oversight for all YHN-SPORE activities and make critical decisions regarding project oversight and management.

PROJECT_TERMS: Acceleration;Administrator;Advocacy;Advocate;anti-cancer research;Basic Science;career development;Clinical Research;Collaborations;Communication;Consultations;cost effective;Development;Disease;Disputes;Ensure;Evaluation;Foundations;Fox Chase Cancer Center;Fund Raising;Funding;Generations;Grant;Head and Neck Cancer;Head and neck structure;Human Resources;Human Subject Research;Institution;Laboratory Finding;Leadership;Malignant neoplasm of lung;medical schools;meetings;Mentors;Modeling;Monitor;National Cancer Institute;neoplasm resource;North Carolina;novel;Occupational activity of managing finances;operation;outreach;Pathway interactions;Patients;Preparation;Principal Investigator;Privatization;Program Development;Program Evaluation;programs;Progress Reports;Publications;Regulation;Reproduction spores;Research;Research Personnel;Research Priority;Research Project Grants;Resources;Science;Series;Site;Source;success;therapy resistant;timeline;translational applications;translational goal;Translational Research;translational scientist;translational study;Translations;United States National Institutes of Health;Universities;website development;Work;Yale Cancer Center

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Rare Diseases

PHR: Narrative The Biospecimen Core provide unified comprehensive tissue management for the HNC SPORE. This includes tissue collection for banking and from clinical trials, as well as cell lines collection and tissue analysis including nucleic acid sequencing and immunohistochemistry, quantitative fluorescence and imaging mass cytometry

PI_NAMEs: RIMM, DAVID L (contact)

PROJECT_TERMS: biobank;Biopsy;Blood;career;Cell Line;Clinical;Clinical Trials;Code;Collection;Communities;Cytometry;Data;Databases;design;Development;digital;DNA sequencing;Excision;Fluorescence;Formalin;Fox Chase Cancer Center;Freezing;Future;Genomics;Grant;Head and Neck Cancer;head and neck cancer patient;Head and Neck Squamous Cell Carcinoma;Head and neck structure;Human;Image;Immunohistochemistry;In Situ;Institution;Maintenance;Measurement;Messenger RNA;MicroRNAs;molecular pathology;nano-string;Neoplasm Metastasis;Nucleic acid sequencing;Paraffin Embedding;Pathologic;Pathology;Patients;Preparation;programs;prospective;Proteins;Provider;Recurrence;Reproduction spores;Research;Resources;sample collection;Serum;Services;Specimen;therapy resistant;Tissue Banks;tissue resource;Tissues;Work

PROJECT_TITLE: Biospecimen Core


NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Rare Diseases

PHR: Project Narrative Well-designed, executed, and analyzed studies are critical to advancing the treatment and care of patients with head and neck cancers. Biostatistics and bioinformatics have critical roles in the design, analysis, and interpretation of data from these studies that help to inform treatment and prevention strategies.

PI_NAMEs: TOWNSEND, JEFFREY PETER (contact)

PROJECT_TERMS: Address;Adverse event;Basic Science;Bioinformatics;Biometry;Biostatistics Core;career development;Clinical;Clinical Research;Clinical Sciences;Clinical Trials;Collaborations;Collection;Communication;Computers;Computing Methodologies;Consultations;Data;Data Analyses;data management;data mining;Databases;design;Development;Employment;Ensure;Experimental Designs;Faculty;Fox Chase Cancer Center;frontier;Funding;Futility;genomic data;Goals;Head and Neck Cancer;Head and neck structure;Individual;Informatics;innovation;Investigation;Laboratories;Leadership;Malignant Neoplasms;Manuscripts;Medicine;meetings;member;Methodology;Methods;Monitor;Monitoring Clinical Trials;multidimensional data;next generation;next generation sequencing;Patient Care;Physicians;Play;Policies;Population;Population Sciences;Population Study;pre-clinical;Prevention strategy;Privacy;Procedures;Program Development;programs;Publications;Randomized;Reproduction spores;Research;research and development;Research Personnel;Research Proposals;Resources;Role;Safety;Sample Size;Schedule;Science;Sequence Analysis;Services;Suggestion;System;therapy resistant;tool;Translational Research;translational study;treatment strategy;web-accessible;Work;Writing;Yale Cancer Center

PROJECT_TITLE: Bioinformatics and Biostatistics Core


NIH_SPENDING_CATS: Clinical Research;Genetics;HIV/AIDS;Infectious Diseases;Kidney Disease

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: PROJECT NARRATIVE A major barrier to HIV cure is the presence of viral reservoirs, cells or tissues in the body where the virus can hide in an inactive state during treatment with antiretroviral medications. The kidney is a site of HIV infection, but it is unknown whether virus from the kidney is capable of reactivating in the absence of antiretroviral medications. This study will determine whether and how HIV can replicate and persist in the kidney, and whether HIV from the kidney can re-emerge in the urine or blood when antiretroviral medications are discontinued.

PI_NAMEs: BLASI, MARIA  (contact);OLABISI, OPEYEMI AYODEJI

PROGRAM_OFFICER_NAME: NIHALANI, DEEPAK

PROJECT_TERMS: Affect;Aftercare;AIDS-Associated Nephropathy;Anti-Retroviral Agents;antiretroviral therapy;APOL1 gene;Archives;Automobile Driving;Autopsy;Base Sequence;Biopsy Specimen;Blood;CD4 Positive T Lymphocytes;Cell Death;Cell Proliferation;Cells;Chronic Disease;chronic infection;Clonal Expansion;Coculture Techniques;Consent;Data;Detection;Development;Epithelial Cells;experience;fighting;follow-up;Frequencies;Gene Expression;Gene Expression Profile;Genes;Genetic;Genetic Recombination;Genitourinary system;Genomic DNA;Growth;HIV;HIV Infections;HIV Seropositivity;HIV-1;Hypertrophy;Immune;improved;In Vitro;in vivo;in vivo evaluation;Individual;induced pluripotent stem cell;Infection;Infiltration;integration site;Interruption;Kidney;kidney allograft;kidney biopsy;kidney cell;Kidney Diseases;kidney infection;Kidney Transplantation;Location;longitudinal analysis;Macrophage;Morbidity - disease rate;mortality;organ injury;Pathogenesis;Pathology;Pathway interactions;Patients;Peripheral Blood Mononuclear Cell;Persons;Pharmaceutical Preparations;Phenotype;Phylogenetic Analysis;Plasma;podocyte;Proliferating;Property;prospective;Protocols documentation;renal epithelium;Renal tubule structure;Reporting;Research;risk variant;Role;Sampling;single-cell RNA sequencing;Site;Source;Specimen;System;T-Lymphocyte;Terminal Disease;Terminally Ill;Time;Tissues;Transplantation;Urine;urogenital tract;Viral;viral detection;Viral Load result;Viral Pathogenesis;viral rebound;Viral reservoir;viral RNA;Virus;Virus Latency;Virus Shedding;Work

PROJECT_TITLE: Mechanisms of HIV persistence in the kidney


ORG_CITY: SANTA BARBARA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA BARBARA

PHR: Project Narrative  By investigating the structure, function, and evolution of selected emerging PLP-dependent enzymes, our work will expand the biocatalytic toolbox for the biocatalytic synthesis of pharmaceutically important noncanonical amino acid building blocks. Besides, our work will also uncover unknown function of a human PLP- dependent enzyme, which will shed new light on human metabolism, health, and physiology.

PI_NAMEs: HAI, YANG  (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TITLE: Understanding the specificity and non-native catalytic activity of PLP-dependent enzymes


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Orphan Drug;Radiation Oncology;Rare Diseases

ORG_CITY: NEW HAVEN

PHR: NARRATIVE A major challenge for improving the efficacy of EGFR targeted therapies (such as cetuximab) in HNSCC is to identify and address cellular mechanisms of therapeutic resistance. We have designed model systems at the molecular, cellular, and tumor levels to analyze cetuximab resistance and to test both antibody-based and small molecule-based therapeutic approaches that block this signaling axis. Combined with an analysis of cetuximab treated patient tumor samples, the overarching goal of this project is to evaluate mechanistically novel EGFR family-targeted treatments in preclinical models of HNSCC.

PI_NAMEs: LEMMON, MARK A (contact)

PROJECT_TERMS: Address;Antibodies;autocrine;Basic Science;biobank;Biochemical;Biological Models;biomarker identification;Biophysics;cancer cell;Cell Line;Cell Survival;Cells;Cetuximab;Clinic;Clinical;clinical translation;Clinical Trials;co-clinical trial;Dependence;design;Eastern Cooperative Oncology Group;effectiveness evaluation;efficacy testing;Engineering;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Epitopes;ERBB3 gene;Event;exome sequencing;Family;Family member;Generations;Genetic;Genetic Markers;Goals;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Head and neck structure;improved;In Vitro;in vivo;inhibitor;Investigation;kinase inhibitor;Knowledge;Ligands;Malignant neoplasm of lung;Mediating;model design;Modeling;Molecular;Molecular Conformation;Molecular Target;Mus;Mutation;Neuregulin 1;novel;novel strategies;novel therapeutic intervention;novel therapeutics;participant enrollment;patient derived xenograft model;Patients;Phase;Phase II Clinical Trials;Pre-Clinical Model;Preclinical Testing;preference;preservation;prevent;radiation response;Radiation therapy;receptor;Receptor Signaling;Resistance;resistance mechanism;response;Sampling;Signal Transduction;small molecule;Specimen;Structure;success;Systemic Therapy;targeted treatment;Testing;Therapeutic;Therapeutic antibodies;Therapeutic Uses;therapy resistant;Tissues;treatment response;tumor;Tumor Markers;Tumor-infiltrating immune cells;Tyrosine Kinase Inhibitor;Up-Regulation;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Project 1: Improved Targeting of EGFR Family Members in Squamous Cell Carcinomas of the Head and Neck


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Immunotherapy;Precision Medicine;Rare Diseases

PHR: Narrative Head and neck cancers often mutate TP53 and CDKN2A, reducing G1/S checkpoints; this leads to resistance to some treatments, but creates tumor-specific vulnerabilities to drugs targeting G2/M checkpoints. We identified three drug combinations for which simultaneous application of two drugs targeting G2/M was much more active than either drug alone, with a lead combination showing strong efficacy and no toxicity in a mouse xenograft model for head and neck cancer. The project will establish the mechanism of drug combination effectiveness, identify response biomarkers, determine how various complements of TP53 and CDKN2A mutations affect response, and perform a clinical trial to assess combination drug activity in head and neck tumors in humans.

PROJECT_TERMS: Acceleration;Affect;Aneuploidy;anti-cancer;Apoptosis;aurora kinase A;Biological Markers;biomarker identification;cancer cell;CASP3 gene;CDC2 gene;CDKN2A gene;Cell Cycle;Cell Cycle Arrest;Cell Cycle Checkpoint;Cell Line;Cell Survival;Cells;Centrosome;Characteristics;checkpoint inhibition;CHEK1 gene;Cisplatin;Clinic;Clinical;Clinical Trials;cohort;Cyclin-Dependent Kinases;cytotoxic;cytotoxicity;Data;Defect;Dependence;DNA Damage;DNA Repair;DNA Sequence Alteration;Doctor of Philosophy;Dose;Drug Combinations;Drug Targeting;effective therapy;Effectiveness;Enrollment;Evaluation;Exhibits;exome sequencing;experimental study;Freezing;Future;G1/S Checkpoint Pathway;gain of function;Generations;Genes;genomic biomarker;Genomics;Goals;Head and Neck Cancer;Head and Neck Neoplasms;Head and Neck Squamous Cell Carcinoma;HPV negative;HPV-negative head and neck cancer;Human;Inflammatory;inhibitor;kinase inhibitor;Lead;Malignant Neoplasms;Measures;Mitosis;Mitotic;Mitotic spindle;Modeling;Mus;Mutate;Mutation;neoantigens;Normal Cell;Normal tissue morphology;novel;Operative Surgical Procedures;patient biomarkers;patient derived xenograft model;Patient Selection;Patients;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Phase;Phenotype;Phosphorylation;Phosphotransferases;PLK1 gene;Ploidies;Population;pre-clinical;predictive marker;preservation;Protein Dephosphorylation;Protein-Serine-Threonine Kinases;Recommendation;repaired;replication stress;Resectable;Resistance;response;response biomarker;Serine;Signal Transduction;single cell sequencing;synergism;targeted agent;Testing;therapy resistant;Toxic effect;TP53 gene;Translating;translational impact;tumor;Tumor Suppressor Proteins;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Project 2: Synthetic Lethal Therapy for HPV-Negative Head and Neck Cancer


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Clinical Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hypertension;Infectious Diseases;Mental Health;Mental Illness;Prevention;Sleep Research;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative: Violence, substance use, sleep disturbances, and hypertension among women with HIV: A syndemic approach (VS2H2 Syndemic) Leveraging the resources of Women’s Interagency HIV study and building on previous work related to the syndemic of substance abuse, violence, and HIV/AIDS, the objective of this proposal is to understand how syndemic factors longitudinally impact sleep disturbances and hypertension among women with HIV (WWH) who are confronting distinct social, neighborhood, and economic realities. We also seek to clarify the interaction, mediators, and directionality linking these multi-level syndemic factors and co-morbid health outcomes. The results of the study will generate important insights for policies and multi-sectoral interventions to alleviate social and health inequities among WWH both in the US and worldwide.

PI_NAMEs: LIM, SAHNAH  (contact)

PROGRAM_OFFICER_NAME: COADY, SEAN

PROJECT_TERMS: Behavior;black women;comorbidity;Data;Development;Disadvantaged;Disease;Economics;Face;gender-based violence;Health;Health behavior and outcomes;health inequalities;High Prevalence;High Risk Woman;HIV;HIV/AIDS;Hypertension;Incidence;Income;Individual;insight;Intercept;interest;Intervention;Investigation;Link;Measures;Mediator;Mental Depression;Mental disorders;Mental Health;Methodology;Modeling;Neighborhoods;Outcome;Pathway Analysis;Pathway interactions;Policies;Population;Predictive Factor;Prospective Studies;Race;Research Personnel;Resources;Risk Factors;Site;Sleep;Sleep disturbances;Sleeplessness;social;Social Network;Stigmatization;Substance abuse problem;substance use;syndemic;Violence;Visit;Woman;Women's Health;Women's Interagency HIV Study;Work