ED_INST_TYPE: SCHOOLS OF SOCIAL WELFARE/WORK

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Clinical Research;Data Science;Emergency Care;Health Services;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Patient Safety;Prevention;Serious Mental Illness;Suicide;Suicide Prevention

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Although patients with mental disorders who present to emergency departments have over a 30-fold increased odds of suicide, most are not identified as at risk during these visits. This project will apply machine learning methods to electronic health records and medical claims in order to develop and evaluate point-in-time short- term longitudinal suicide risk algorithms for patients presenting to the emergency department with mental health complaints. This new knowledge will provide emergency department clinicians with interpretable, patient-specific information about short-term risk of suicide attempts and suicide.

PI_NAMEs: MARCUS, STEVEN C (contact);OLFSON, MARK

PROGRAM_OFFICER_NAME: HAIM, ADAM J

PROJECT_TERMS: Accident and Emergency department;Address;Algorithms;analytical method;Artificial Intelligence;Caring;Cessation of life;Characteristics;Clinical;Clinical Data;clinical decision support;clinical encounter;clinical risk;Complex;Computational algorithm;Crisis Intervention;Data;Data Analytics;data mining;Data Set;Data Sources;Databases;Development;Diagnosis;Drug Prescriptions;Electronic Health Record;Emergency Care;Emergency Department evaluation;Emergency Department Physician;Emergency department visit;Emergency Medicine;emergency settings;Event;explainable machine learning;follow-up;Health;health service use;Healthcare Systems;high risk;improved;indexing;innovation;insight;interest;Intervention;Knowledge;Link;Machine Learning;machine learning method;machine learning model;Medical;Mental disorders;Mental Health;Mental Health Services;Methods;model development;Modeling;Organizational Models;Outcome;Outpatients;Output;Patients;Pattern;Persons;Physicians;prediction algorithm;predictive modeling;Prevention;Procedures;Process;prototype;Provider;Psychiatrist;Public Health;Recording of previous events;Research;Resources;Risk;Risk Assessment;Risk Factors;Risk Management;risk prediction;Services;suicidal;suicidal behavior;suicidal morbidity;suicidal patient;suicidal risk;Suicide;Suicide attempt;Suicide prevention;support tools;Symptoms;Techniques;Time;trait;Translating;Update;Visit

PROJECT_TITLE: Development and clinical interpretation of machine learning emergency department suicide prediction algorithms using electronic health records and claims

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: College Station

ORG_COUNTRY: UNITED STATES

ORG_DEPT: VETERINARY SCIENCES

ORG_FIPS: US

ORG_NAME: TEXAS A&M AGRILIFE RESEARCH

ORG_STATE: TX

PHR: Poxviruses comprise a large family of viruses including species that are highly pathogenic for humans as well as animals. Members of poxviruses are also being employed as recombinant vectors for vaccines and potential cancer therapeutics. The outcomes from this project to study non-canonical open reading frames may ultimately lead to novel intervening strategies and improving poxviruses as vaccine vectors and cancer therapeutics agents.

PI_NAMEs: YANG, ZHILONG  (contact)

PROGRAM_OFFICER_NAME: KNISELY, JANE M

PROJECT_TERMS: Amino Acids;Animals;Biochemical;Biological;Biological Assay;Biological Process;Biology;biothreat;Cell Physiology;Cells;Chemicals;Communicable Diseases;Development;Family;fighting;Foundations;Future;Gene Expression;Genetic Engineering;Genetic study;Genetic Transcription;Genome;genome-wide;genome-wide analysis;Human;improved;Intervention;Investigation;Knowledge;Length;Malignant Neoplasms;Mass Spectrum Analysis;member;Membrane;Messenger RNA;Monkeypox virus;N-terminal;novel;novel strategies;Nucleotides;oncolytic virotherapy;Open Reading Frames;Organism;Outcome;pathogen;Pathogenicity;Peptides;Play;Poxviridae;Poxviridae Infections;prevent;Production;protein expression;protein function;Proteins;prototype;Recombinants;Resolution;ribosome profiling;Ribosomes;Role;Site;Smallpox;smallpox eradication;Therapeutic;Therapeutic Agents;Transcription Initiation Site;transcriptome sequencing;Translating;Translation Initiation;Untranslated RNA;Vaccines;Vaccinia virus;Variola major virus;vector vaccine;Viral;Viral Genome;Virus;Virus Diseases;Virus Replication;Western Blotting;Zoonoses

PROJECT_TITLE: Poxvirus-encoded noncanonical open reading frames

STUDY_SECTION: MCV

STUDY_SECTION_NAME: Molecular and Cellular Biology of Virus Infection Study Section[MCV]


ADMINISTERING_IC: AT

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

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);Brain Disorders;Cerebrovascular;Complementary and Integrative Health;Dementia;Lymphatic Research;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: CAMBRIDGE

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

ORG_STATE: MA

PHR: The glymphatic and meningeal lymphatic clearance systems play a critical role in the removal of toxic amyloid and tau burden associated with Alzheimer's disease (AD) from the brain. We recently found that application of GENUS, a noninvasive regime using patterned light and sound to elicit gamma entrainment, reduced the accumulation of amyloid and tau and ameliorated cognitive functions in multiple disease mouse models, but the beneficial effects by which GENUS potentially impacts the brain clearance system are not clear. We will identify the effects and potential mechanisms by which GENUS impacts the physiological, cellular, and molecular responses of and subsequent clearance of AD-associated toxic amyloid by the glymphatic and meningeal lymphatic systems.

PI_NAMEs: TSAI, LI-HUEI  (contact)

PROGRAM_OFFICER_NAME: BELFER, INNA

PROJECT_TERMS: Ablation;Acceleration;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid;Amyloid Proteins;Anesthetics;aquaporin 4;Astrocytes;Attenuated;Automobile Driving;awake;Blood Vessels;Brain;Brain Diseases;brain parenchyma;Carotid Stenosis;Cells;Cerebrospinal Fluid;Cerebrovascular system;Chronic;cisterna magna;cognitive function;Complementary Health;Coupled;Dextrans;Diameter;dietary supplements;Disease;Drainage procedure;Endothelial Cells;Excision;Exhibits;Extravasation;fitness;Fluorescence Microscopy;Fluorescence-Activated Cell Sorting;Frequencies;Gap Junctions;Genetic Transcription;glymphatic clearance;glymphatic dysfunction;glymphatic flow;glymphatic system;Healthcare;hyperphosphorylated tau;immunoregulation;Impaired cognition;Impairment;improved;in vivo;insight;Integrative Medicine;Intercellular Fluid;Laser injury;Light;Liquid substance;Literature;loss of function;lymph flow;Lymphatic clearance;Lymphatic Diseases;lymphatic drainage;Lymphatic function;Lymphatic System;lymphatic vessel;Maps;Mediating;Meningeal;Meningeal lymphatic system;Meninges;Metabolic;Microglia;Microscopy;mindfulness;Molecular;Monitor;Morphology;mouse model;Movement;Mus;Music Therapy;neural;Neurons;neurotoxic;neurovascular;neurovascular coupling;neurovascular unit;Nitric Oxide;novel therapeutic intervention;Optics;Pathogenicity;Pathology;Pathway interactions;Pattern;Pericytes;pharmacologic;Physical Exercise;Physiological;Play;Population;Potassium;Process;programs;protein aggregation;Proteins;recruit;Regimen;response;Role;Sensory;sensory stimulus;Signal Transduction;single-cell RNA sequencing;Sleep;Smooth Muscle Myocytes;solute;sound;System;tau aggregation;tau Proteins;Tauopathies;Testing;Tracer;two-photon;Vasoactive Intestinal Peptide;vasomotion;wasting;water channel

PROJECT_TITLE: Noninvasive sensory stimulation to promote glymphatic-lymphatic clearance for the treatment of Alzheimer’s Disease


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Immunotherapy;Lung;Lung Cancer

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Approximately two-thirds of patients diagnosed with cancer in the United States will be cured of their disease using a combination of surgery, radiation and chemotherapy, but progress towards enhanced survival in adults with advanced and metastatic disease has been painfully slow, even in the era of targeted therapies, and new, more effective therapies are desperately needed. MERTK and AXL, members of the TAM-family of receptor tyrosine kinases, are aberrantly expressed in a wide variety of different tumor types and are potential therapeutic targets in majority of human tumors, therefore, agents targeting both MERTK and AXL may be particularly effective. The studies described here aim to develop potent and selective dual MERTK and AXL inhibitors suitable for clinical application and as such, may have a direct impact on outcomes and/or quality of life for patients with advanced cancers.

PI_NAMEs: GRAHAM, DOUGLAS K;WANG, XIAODONG  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: ABCG2 gene;Adult;Advanced Malignant Neoplasm;Antibodies;Biochemical;Biological Assay;Bypass;cancer cell;Cancer cell line;Cancer Model;cancer therapy;Carcinoma;cell killing;Cell Physiology;Cell Survival;Cells;Cellular Assay;Chemoresistance;Chemotherapy and/or radiation;clinical application;clinical efficacy;Clinical Trials;Co-Immunoprecipitations;Combined Modality Therapy;Computing Methodologies;Cytotoxic Chemotherapy;Data;design;Development;Diagnosis;Disease;Distant Metastasis;Early treatment;effective therapy;Environment;Event;Family;Family member;Human;Immune;Immunocompetent;In Vitro;in vivo;inhibitor;Innate Immune Response;Innate Immune System;Lead;lung cancer cell;Macrophage;Malignant Neoplasms;Mediating;member;MERTK gene;Methods;molecular dynamics;Molecular Target;Motility;Mus;Mutation;Natural Killer Cells;Neoplasm Metastasis;neoplastic cell;Newly Diagnosed;Non-Small-Cell Lung Carcinoma;novel;Oncogenic;Operative Surgical Procedures;Outcome;Pain;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacodynamics;Phenotype;Phosphorylation;Phosphotransferases;Play;pre-clinical;Prognosis;Property;Proteins;Quality of life;Receptor Protein-Tyrosine Kinases;Resistance;Resistance development;response;Role;Signal Pathway;Signal Transduction;small molecule inhibitor;Structure;subcutaneous;Support System;Survival Rate;targeted agent;targeted treatment;Testing;Therapeutic;therapeutic target;therapeutically effective;Toxic effect;tumor;tumor growth;Tumor Immunity;Tumor-associated macrophages;tumorigenesis;TYRO3 gene;Tyrosine Kinase Inhibitor;United States;validation studies;Work;Xenograft Model

PROJECT_TITLE: MERTK/AXL dual inhibitors provide novel treatment for cancer by targeting tumor cells and activating anti-tumor immunity

STUDY_SECTION: DMP

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


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Neurodegenerative;Prevention;Social Determinants of Health

ORG_STATE: PA

PHR: Summary This proposal aims to develop new causal inference methods to tame bias due to hidden confounding factors in obser- vational studies as well as in randomized experiments subject to non-adherence. The proposed methods are firmly grounded in modern semiparametric theory which will be used to obtain more robust and efficient inferences about causal effects in a broad range of public health applications including in Epidemiology of Aging, Environmental Health Epidemiology and HIV/AIDS Prevention.

PI_NAMEs: TCHETGEN TCHETGEN, ERIC JOEL (contact)

PROGRAM_OFFICER_NAME: KING, JONATHAN W

PROJECT_TERMS: Address;Adherence;Africa;Aging;AIDS prevention;Air Pollution;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;ambient air pollution;analytical method;Area;Blood Pressure;Body mass index;Botswana;Cluster randomized trial;comparative;Data;design;Diabetes Mellitus;Disease;Environmental Health;Epidemiology;experimental study;Genetic;genetic variant;Health;Health Sciences;high dimensionality;HIV;Incidence;Interruption;Intervention;intervention effect;Learning;Linkage Disequilibrium;Literature;Machine Learning;Masks;Mendelian randomization;Methodology;Methods;Modeling;Modernization;modifiable risk;mortality;novel;Observational Study;Outcome;Participant;pleiotropism;Process;Public Health;Public Health Applications Research;Randomized;Research Design;Research Personnel;Risk Factors;semiparametric;Series;simulation;Social Sciences;Testing;theories;Time;treatment as prevention;treatment effect;uptake;user friendly software

PROJECT_TITLE: Novel Designs and Methods to Remove Hidden Confounding Bias in Health Sciences

STUDY_SECTION: BMRD

STUDY_SECTION_NAME: Biostatistical Methods and Research Design Study Section[BMRD]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Genetics;Regenerative Medicine;Wound Healing and Care

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE The characterization of innate immune regulation of skin wound-repair will provide insights into the pathology and therapeutic options for autoimmune/autoinflammatory skin conditions such as psoriasis and atopic dermatitis. The identification of molecular mechanisms that trigger skin-wound repair will contribute to our understanding and treatment for conditions associated with chronic non-healing wounds such as diabetic ulcers, epithelial cancer, and poor wound-repair associated with aging.

PI_NAMEs: LIU, SIQI  (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: adaptive immunity;adult stem cell;Affect;Aging;Atopic Dermatitis;Autoimmune;autoinflammatory;Biochemical;Biology;Carcinoma;career development;Cell Death;cell injury;Cell membrane;Cells;Chronic;Complex;cytokine;diabetic ulcer;Disease;Environment;Epidermis;Epithelium;Event;Family;Gene Expression Profiling;Genetic;Genetic Models;Goals;Growth Factor;Hair follicle structure;Host Defense;Immune;immune cell infiltrate;Immune signaling;Immune system;Immunology;immunoregulation;improved;in vitro Assay;in vivo;injured;Injury;innate immune sensing;Innate Immune System;insight;Investigation;keratinocyte;Knock-out;Knowledge;Ligands;Mechanics;Mediating;Mentors;Methods;migration;Modeling;Molecular;Necrosis;non-healing wounds;novel;Outcome;pathogen;Pathology;Pattern;Pattern recognition receptor;Positioning Attribute;Process;Production;Proliferating;Psoriasis;re-epithelialization;Receptor Signaling;recruit;repaired;Research;Research Personnel;response;Role;Signal Induction;Signal Pathway;Signal Transduction;Site;Skin;Skin repair;skin wound;Study Subject;T-Lymphocyte;Technical Expertise;Therapeutic;tissue regeneration;Tissues;tool;Training;transcription factor;Transcriptional Activation;Trauma;Universities;wound;wound closure;wound healing;wound injury;γδ T cells

PROJECT_TITLE: Innate immune regulation of wound re-epithelialization

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Neurodegenerative;Neurosciences;Prevention;Rehabilitation

ORG_CITY: MADISON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Persons with Alzheimer’s Disease and Related Dementias (AD/ADRD) frequently suffer from dysphagia, an impaired ability to swallow food and drink, that can lead to serious health consequences such as malnutrition, decreased quality of life, increased care partner burden, and pneumonia. However, there are major gaps in our understanding of how swallowing function declines over time and risk factors for this condition in persons with AD/ADRD. This project aims to comprehensively characterize swallowing function in persons with AD/ADRD to inform the development of improved methods to identify, prevent, and treat this serious condition.

PI_NAMEs: ROGUS-PULIA, NICOLE M (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Address;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease related dementia;Aspiration Pneumonia;Biological Markers;Biomechanics;Caregiver Burden;Caring;Characteristics;Clinical;clinical care;Clinical dementia rating scale;Clinical Management;Clinical stratification;Cognition;cohort;comorbidity;Complex;Cross-Sectional Studies;Deglutition;Deglutition Disorders;Dementia;demographics;Detection;Deterioration;Development;Disease Progression;Disease stratification;dysphagia rehabilitation;effective therapy;effectiveness evaluation;efficacy evaluation;Enrollment;Epidemiology;Evaluation;experience;follow-up;Food;Foundations;functional decline;Functional disorder;Generations;Goals;Health;high risk population;Impaired cognition;Impairment;improved;innovation;Intervention;Knowledge;Malnutrition;Manometry;Measures;Methods;mortality;multi-site trial;multidisciplinary;multimodality;Nature;Nerve Degeneration;neural;Neuropsychological Tests;Neuropsychology;novel;Nutritional status;Oral;Oral health;Outcome;Outcome Measure;Participant;Patient Outcomes Assessments;Perception;Persons;Pharyngeal structure;Phase;Physiology;Plasma;Pneumonia;Population;pressure;Prevalence;prevent;Prevention;Production;Prospective cohort;Prospective, cohort study;Quality of life;Rehabilitation therapy;Reporting;Research;Resolution;respiratory;Respiratory physiology;Risk;Risk Factors;Saliva;sarcopenia;screening;Subgroup;Symptoms;System;Therapeutic;therapy development;Time Factors;Visit;Work

PROJECT_TITLE: Swallowing Trajectories and DysPHagia Predictors in AlzheimER’s DisEase (SPHERE)

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Heart Disease;Mental Health;Neurodegenerative;Neurosciences;Prevention;Rehabilitation

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE  This research project is relevant to public health because both heart failure (HF) and mild cognitive impairment (e.g., trouble remembering and concentrating beyond normal aging) are highly prevalent among older adults in the United States. Despite advances in health care, there are no effective interventions for treating cognitive impairment in HF, which if left untreated, leads to suboptimal health, quality of life, and shorter survival. Therefore, we propose to test the effect of a dual-component intervention comprised of a virtual reality-based cognitive restoration intervention and computerized cognitive training on cognitive function and overall health among 172 older adults with HF who experience mild cognitive impairment.

PI_NAMEs: JUNG, MIYEON  (contact)

PROGRAM_OFFICER_NAME: FRANKOWSKI, DAVID WITT

PROJECT_TERMS: Address;Adult;Affect;Age;Aging;Alleles;Alzheimer's disease related dementia;American;Apolipoprotein E;Attention;Award;Biological Markers;Biometry;Brain-Derived Neurotrophic Factor;Cardiology;cardiovascular nursing;career development;Caring;Clinical Trials;Cognition;Cognitive;cognitive benefits;cognitive function;cognitive training;computerized;Death Rate;Dementia;dementia risk;depressive symptoms;design;Diagnosis;disability;Doctor of Philosophy;Educational Intervention;Educational workshop;effective intervention;efficacious intervention;Enrollment;Environment;Evaluation;experience;follow-up;functional independence;Funding;Future Generations;Genetic Markers;Goals;head-to-head comparison;Health;health management;health related quality of life;Healthcare;Heart failure;high risk;Human;human old age (65+);Impaired cognition;improved;Individual;instrumental activity of daily living;Interdisciplinary Study;interest;Intervention;intervention effect;Leadership;Left;life span;Longterm Follow-up;medical specialties;Medication Management;meetings;Memory;Mentors;mild cognitive impairment;mortality;multidisciplinary;Neurology;Neuronal Plasticity;normal aging;novel;older adult;older patient;Outcome;participant enrollment;patient retention;Patients;Persons;Physical Exercise;pilot trial;Population;post intervention;primary outcome;Public Health;Quality of life;Randomized;Randomized, Controlled Trials;Research;Research Personnel;Research Project Grants;research study;restoration;Running;Self Care;Severities;skills;Solid;standard of care;Technology;Testing;theories;Training;Training Activity;treatment as usual;Treatment Efficacy;United States;virtual reality;Vulnerable Populations;Work

PROJECT_TITLE: Virtual Reality and Computerized Cognitive Intervention for Mild Cognitive Impairment in Heart Failure


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Cocaine;Drug Abuse (NIDA only);Endocannabinoid System Research;Methamphetamine;Neurosciences;Opioid Misuse and Addiction;Opioids;Stimulant Use and Misuse;Substance Misuse;Therapeutic Cannabinoid Research

ORG_CITY: STANFORD

ORG_DEPT: NEUROSURGERY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Project Narrative While the recent national focus has been on the opioid crisis, 1 million Americans suffer from methamphetamine use disorder and 1 million more from cocaine use disorder, with stimulants being the second leading cause of overdose deaths behind opioids. However, unlike opioids, there is currently no pharmacological treatment approved by the FDA for stimulants. This project aims to collaborate with the Blueprint Neurotherapeutics Network (BPN) team for lead optimization of our novel, cyclase-biased, selective cannabinoid receptor 2 (CB2R) agonists class, developed at Stanford with support from a U18 NIDA pilot grant, into preclinical/clinical development for the treatment of methamphetamine use disorder.

PI_NAMEs: SHAMLOO, MEHRDAD  (contact)

PROGRAM_OFFICER_NAME: CYWIN, CHARLES L

PROJECT_TERMS: absorption;addiction;Addictive Behavior;Affect;aged;Agonist;American;Amphetamine Addiction;analog;animal efficacy;Animal Model;Animals;ARRB2;Arrestins;Behavior;beta-arrestin;Biological Assay;Biology;Brain;Buprenorphine;cannabinoid receptor;Cannabinoids;Cells;Central Nervous System;Cessation of life;chemical synthesis;Chemicals;Clinical;clinical candidate;clinical development;Clinical Trials;CNR1 gene;CNR2 gene;Cocaine;Cocaine use disorder;Collaborations;conditioned place preference;course development;Cyclic AMP;Data;desensitization;design;Development;Dopamine;dopamine system;dopaminergic neuron;Dose;drug discovery;efficacy study;endogenous cannabinoid system;Engineering;Epidemic;Face;Failure;FDA approved;Feasibility Studies;Formulation;Funding;Goals;Grant;Heroin;Heroin Dependence;Human;Hyperactivity;Illicit Drugs;illicit opioid;In Vitro;in vivo;Intervention;Investments;Lead;lead candidate;lead optimization;lead series;manufacture;Manufactured Materials;MAPK3 gene;Marijuana;Maximum Tolerated Dose;Mediating;Medical Marijuana;Medicine;Methadone;Methamphetamine;Methamphetamine use disorder;Microglia;Modeling;multidisciplinary;Mus;National Institute of Drug Abuse;Neurons;novel;Nucleus Accumbens;Opiate Addiction;Opioid;opioid epidemic;opioid use disorder;Oral;Outcome;overdose death;Pain;Pathway interactions;Penetration;Phagocytosis;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Pharmacology;Phase;phase 1 designs;Phase I Clinical Trials;Play;Polymorph;pre-clinical;preclinical development;preclinical study;Preparation;prescription opioid;programs;Property;Psychiatry;Rattus;receptor;research clinical testing;Residual state;Rodent;Role;Safety;safety and feasibility;safety study;scale up;screening;Self Administration;Severities;Signal Transduction;social;socioeconomics;Sodium Chloride;species difference;Specificity;Stimulant;stimulant abuse;stimulant dependence;stimulant use;stimulant use disorder;Substance Use Disorder;Testing;therapeutic development;therapy development;Toxicogenetics;Toxicology;Validation;Ventral Tegmental Area

PROJECT_TITLE: Development of selective cannabinoid receptor 2 agonists for treatment of addiction


ADMINISTERING_IC: HD

ED_INST_TYPE: UNIVERSITY-WIDE

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

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dental, Oral, and Craniofacial Disease;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Intellectual and Developmental Disabilities (IDD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Social Determinants of Health

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative This research proposal aims to improve the diagnostic capabilities of detecting neurodevelopmental delay in resource-limited settings such as Malawi to evaluate the impact of chewing a low-cost, xylitol gum during pregnancy compared to no xylitol gum on rates of neurodevelopmental delay in offspring. This proposal is in alignment with my life-long intent to build a career centered upon improving neonatal outcomes, including neurodevelopment, through innovative, low-cost maternal interventions. I propose to leverage our institutions’ infrastructure in Malawi, global health mentors and leaders, and research expertise in neonatal neurodevelopmental outcomes research to develop a framework that will translate into future neurodevelopmental and interventional studies aimed at improving neonatal outcomes globally.

PI_NAMEs: VALENTINE, GREGORY CHARLES (contact)

PROGRAM_OFFICER_NAME: CHAKHTOURA, NAHIDA ABDO

PROJECT_TERMS: 18 year old;6 year old;Address;Africa South of the Sahara;Age;aged;analytical method;Assessment tool;autism spectrum disorder;Birth;Birth Rate;career;Caring;Child;Cluster randomized trial;Conceptions;Consumption;cost;cost effective;Country;Data;data management;Databases;Dental;Dental caries;design;Detection;Development;Developmental Delay Disorders;Diagnostic tests;diagnostic tool;diagnostic value;early pregnancy;efficacy testing;Epidemiology;Exposure to;Feasibility Studies;Follow-Up Studies;Future;global health;Grant;health disparity;improved;Infection;Inflammation;Inflammatory;Infrastructure;infrastructure development;innovation;Institution;Intervention;intervention cost;Intervention Studies;Knowledge;Learning;Link;Long-Term Effects;low and middle-income countries;Malawi;Mastication;Measures;Mental Depression;Mentors;mortality;Mothers;Neonatal;neonatal health;neonatal outcome;neonate;neurodevelopment;Neurodevelopmental Disability;novel;offspring;Outcome;Outcomes Research;Patients;perinatal intervention;Periodontal Diseases;Periodontitis;Pregnancy;Pregnant Women;premature;Premature Birth;prenatal;prenatal exposure;Preparation;preterm newborn;prevent;Prevention;Quality of life;Random Allocation;Reference Standards;Research;Research Design;Research Infrastructure;Research Proposals;Resource-limited setting;Risk Factors;Sampling;screening;Screening procedure;Sensitivity and Specificity;sex;Shapes;skills;Sugar Substitute;systemic inflammatory response;Testing;Time;tool;Training;Translating;trial enrollment;Validation;Vulnerable Populations;Woman;Writing;Xylitol;xylitol gum

PROJECT_TITLE: Prevention of Developmental Delay and Xylitol (PDDaX) Study

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Pediatrics Study Section[CHHD-A]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Cardiovascular;Clinical Research;Dementia;Mental Health;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Physical Activity;Prevention;Telehealth

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative There is an urgent need to understand how to engage and retain older adults in use of mHealth technologies that permit in-home monitoring of health including cognitive function. In the community-based Framingham Heart Study, we propose to enhance engagement strategies and study factors associated with successful use of a smartphone application and smartwatch in older adults. We will investigate the usefulness of the digital data for monitoring risk factors for Alzheimer’s disease and we will relate the digital data to brain aging outcomes including preclinical Alzheimer’s disease using neuropsychological testing and brain MRI data.

PI_NAMEs: MURABITO, JOANNE M (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Adherence;Adult;adverse outcome;Affect;Age;aging brain;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Anxiety;Apple watch;Behavior;Brain;brain health;brain magnetic resonance imaging;brain volume;cardiovascular health;Cellular Phone;Clinical;Cognition;Cognitive;Cognitive deficits;cognitive function;cohort;Cohort Studies;Communities;COVID-19;COVID-19 pandemic;Data;Dementia;Devices;digital;Digital biomarker;digital data;digital measure;disorder risk;Electronics;Eligibility Determination;Event;executive function;experience;falls;Fatigue;frailty;Framingham Heart Study;Fright;Health;Health behavior;Health Technology;Heart Rate;heart rate variability;high risk;Hippocampus;Home;Hospitalization;human old age (65+);Impaired cognition;Individual;innovation;insight;Knowledge;Language;Life;Link;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Maintenance;Measures;Memory;Methods;mHealth;middle age;Monitor;Moods;mortality risk;Motor Skills;Neuropsychological Tests;novel;offspring;older adult;Older Population;Outcome;Pain;Participant;Patient Outcomes Assessments;Personal Satisfaction;Persons;Phenotype;Physical activity;Physical assessment;Physical Performance;Pilot Projects;Population;pre-clinical;preservation;Prevalence;prospective;Public Health;Recommendation;remote monitoring;Research;Research Personnel;Rest;Risk;Risk Factors;sex;Sleep;smart watch;smartphone application;Social Distance;Social isolation;Social support;Surveys;System;Task Performances;Technology;tool;virtual;Visuospatial;White Matter Hyperintensity

PROJECT_TITLE: Monitoring Health in Older Adults Using mHealth Technology: Framingham Offspring Study

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-C(02)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: NARRATIVE Adenosquamous cancer of the pancreas (ASCP) is a devastating disease with high metastatic potential and a bleak clinical outcome. Despite aggressive surgical and medical managements, the median survival has been reported to be consistently less than 1 year. In this application we propose to investigate the mechanism driving this dismal disease and develop a new approach to treat patients with ASCP.

PI_NAMEs: BORAD, MITESH ;FERNANDEZ-ZAPICO, MARTIN ERNESTO (contact)

PROGRAM_OFFICER_NAME: LIU, ZHIHUI

PROJECT_TERMS: Acetylation;Adenocarcinoma;Adjuvant;Adjuvant Therapy;ATAC-seq;Automobile Driving;Biological;Cancer Etiology;candidate identification;CDKN2A gene;cell growth;Cell Survival;Cells;Cessation of life;Chemicals;chemotherapeutic agent;chemotherapy;Chromatin;chromatin modification;Clinical;cohort;Colon;Cytoplasm;Data;data integration;Diagnosis;Disease;Drug Targeting;Duct (organ) structure;Enzymes;Epigenetic Process;epigenome;epigenomics;Event;expectation;Foundations;gemcitabine;Gene Expression;Genetic;Genetic Transcription;Genome;genomic locus;Genomics;Histology;histone methyltransferase;Histones;Human;Immunodeficient Mouse;Immunofluorescence Immunologic;Impairment;in vivo;Incidence;Individual;insight;Intercellular Junctions;irinotecan;keratinization;KRAS2 gene;Lesion;Lung;Lysine;Maintenance;Malignant neoplasm of pancreas;Malignant Neoplasms;Maps;Measures;Mediating;Medical;Methylation;Minor;Modeling;Molecular;Mutation;novel strategies;novel therapeutic intervention;Operative Surgical Procedures;Organoids;Outcome;pancreatic cancer cells;pancreatic cancer model;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic neoplasm;Patients;Pattern;Persons;Pharmaceutical Preparations;Phenotype;population based;pre-clinical;Precision therapeutics;Proteins;Recurrence;Regulatory Element;Reporting;Resectable;response;Role;Sampling;Signal Pathway;Solid;Sorting;SOX5 gene;Squamous cell carcinoma;Stomach;Surgical Management;Testing;Therapeutic;therapeutic target;Time;Tissues;TP53 gene;transcription factor;transcriptome;transcriptome sequencing;tumor;tumor growth;Tumor stage;Variant;Xenograft procedure

PROJECT_TITLE: New Therapuetics for Pancreatic Cancer


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

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative  As Alzheimer’s disease progresses, pathological forms the tau protein accumulate in progressively more brain regions in a predictable manner by transfer from one brain cell to another. This project investigates how chemical modifications of tau that occur in Alzheimer’s disease influence the transfer of pathological tau from cell to cell. Understanding this process in greater detail will provide deeper insights into the disease process in Alzheimer’s disease and may suggest new treatment strategies for slowing the progression of Alzheimer’s disease.

PI_NAMEs: DICKSON, JOHN R (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: 3-Dimensional;abeta accumulation;Acetylation;Address;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease patient;Amino Acids;Biological Assay;Biology;Biosensor;brain cell;Brain region;career;career development;Cell Culture Techniques;Cell model;Cell Physiology;Cells;Charge;Chemicals;Clinical;Communication;Cytoplasm;Data;Deacetylation;defined contribution;Dementia;design;Development;Development Plans;Disease;endosome membrane;Endosomes;Evaluation;experience;experimental analysis;experimental study;extracellular;Flow Cytometry;Fluorescence Resonance Energy Transfer;Functional disorder;Galectin 3;Grant;immunocytochemistry;Impaired cognition;In Vitro;Induced pluripotent stem cell derived human neuron;innovation;insight;K-Series Research Career Programs;Literature;Luciferases;machine learning algorithm;Manuscripts;meetings;Mentors;Mentorship;Modeling;Modification;Molecular;Molecular Weight;mutant;Mutation;Neuroanatomy;Neurofibrillary Tangles;neuronal circuitry;Neurons;neuropathology;novel therapeutic intervention;Pathologic;Pathology;Pattern;Performance;Phosphorylation;Physicians;Play;Positron-Emission Tomography;Post-Translational Protein Processing;Preparation;Process;Property;Protein Dephosphorylation;protein structure prediction;Publishing;Radiology Specialty;Recombinants;Research;Role;Scientist;skills;Stains;Stereotyping;tau aggregation;tau mutation;tau Proteins;tau-1;Techniques;Testing;Writing

PROJECT_TITLE: The Influence of Tau Post-Translational Modifications on the Propagation of Tau Pathology in Alzheimer's Disease

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Clinicians/Health Professionals Study Section [AGCD-3]


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

ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: The goal of this current application is to fully characterize a new animal model mimicking the tau pathology development and cognitive dysfunction as seen in the early stage of Alzheimer’s disease. We will map the synaptic pathways mediating disease progression by activating or inhibiting specific synapses, and then evaluate the effect of amyloid deposition for acceleration of tau accumulation. Characterization of the new animal model will be beneficial for the development of effective therapeutic interventions.

PI_NAMEs: IKEZU, TSUNEYA  (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: Acceleration;Age;Alzheimer's Disease;Alzheimer's disease pathology;Amyloid deposition;Anatomy;Animal Model;Antibodies;Appearance;behavioral outcome;brain tissue;cell cortex;cell type;Cells;Cognitive;Complement;conditioned fear;Data;Dendrites;dentate gyrus;Dependovirus;Development;Diagnostic;Disease;Disease Progression;Electrophysiology (science);entorhinal cortex;extracellular vesicles;Female;Functional disorder;Gene Expression Profile;Genetic;Goals;hippocampal pyramidal neuron;Hippocampus;Human;Immunoelectron Microscopy;Impaired cognition;Impairment;in vivo;inducible Cre;Injections;insight;invention;Label;LDL-Receptor Related Protein 1;Learning;male;Maps;MAPT gene;Medial;Mediating;Memory impairment;men;microscopic imaging;mild cognitive impairment;Modeling;Molecular;Monitor;mouse model;Mus;Mutate;Neurons;neurophysiology;new therapeutic target;novel;object recognition;overexpression;Parahippocampal Gyrus;Pathology;Pathway interactions;Patients;Phenotype;Phosphorylation;Play;Prefrontal Cortex;Presynaptic Terminals;prevent;prodromal Alzheimer's disease;promoter;Pyramidal Cells;Rabies virus;Radial;receptor;Reporter;Reporting;Research Project Grants;Role;Sampling;Satellite Viruses;sex;sexual dimorphism;Short-Term Memory;Specimen;Staging;Symptoms;Synapses;System;tau aggregation;tau Proteins;tau-1;Testing;Therapeutic;Therapeutic Intervention;therapeutically effective;Tracer;transcriptome sequencing;Transgenic Mice;transmission process;ultra high resolution;uptake;vector;vesicular release;Wolfram Syndrome;Woman

PROJECT_TITLE: Assessment of a novel tau propagation pathway from layer II medial entorhinal cortical neurons to CA1 pyramidal neurons as an early Braak stage mouse model


NIH_SPENDING_CATS: Aging;Arthritis;Genetics;Osteoarthritis

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative The broad, long-term goal of this project is to develop a comprehensive understanding of the regulatory network that regulates the differentiation and maintenance of articular cartilage, which plays a central role in maintaining the low-friction environment of the joint space. A hallmark of cells comprising the articular cartilage is their expression of proteoglycans, such as the protein lubricin, encoded by the Prg4 gene, that lubricates the joint and protects against the development of arthritis. Successful completion of this proposal will provide fundamental new insight into the events that maintain lubricin expression in articular cartilage, with additional implications for regeneration of articular cartilage in degenerative joint diseases including osteoarthritis (OA) or rheumatoid arthritis (RA).

PI_NAMEs: LASSAR, ANDREW BRUCE (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: 3' Untranslated Regions;Address;Adult;aged;Aging;animal old age;Arthritis;articular cartilage;Attenuated;cartilage degradation;Cattle;Cells;Chondrocytes;Competence;Degenerative polyarthritis;Development;DNA Binding Domain;Ectopic Expression;Embryo;Engineering;Enhancers;Environment;Epidermal Growth Factor Receptor;Epiphysial cartilage;Event;Exons;Failure;Fibroblasts;Friction;Genes;Genetic Recombination;Genetic Transcription;Goals;Hallmark Cell;Health;Homeostasis;Human;In Vitro;in vivo;inducible Cre;Injury;insight;joint injury;Joints;juvenile animal;Knee;Knee joint;LoxP-flanked allele;lubricin;Maintenance;Mechanics;Mediating;Meniscus structure of joint;mouse model;Mus;Natural regeneration;novel;Operative Surgical Procedures;Patients;Play;postnatal;programs;protein expression;Proteins;Proteoglycan;Rattus;response;Rheumatoid Arthritis;Role;Sheep;Signal Pathway;Signal Transduction;stem cell population;Surface;Synovial Cell;Synovial Fluid;Synovial joint;tissue regeneration;Tissues;transcription factor;Transforming Growth Factor beta;Transforming Growth Factor Beta 2;Traumatic Arthropathy;Work

PROJECT_TITLE: The Role of Creb5 in Maintaining Synovial Joint Homeostasis

STUDY_SECTION: SBSR

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


ADMINISTERING_IC: GM

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: WALTHAM

ORG_DEPT: BIOLOGY

ORG_NAME: BRANDEIS UNIVERSITY

PHR: Project Narrative The goal of this new graduate student training program is to produce rigorous, quantitatively-minded scientists equipped to solve increasingly complex problems in Molecular and Cellular Biology using integrated, cross-disciplinary approaches. In addition to rigorous coursework and research training, students are provided with layered, individualized career development activities to help prepare for diverse scientific research and other science-related careers.

PI_NAMEs: GARRITY, PAUL  (contact);GOODE, BRUCE L

PROGRAM_OFFICER_NAME: AIYEGBO, MOHAMMED S

PROJECT_TERMS: Molecular and Cellular Biology;pre-doctoral;Training

PROJECT_TITLE: Predoctoral Training in Cross-disciplinary Molecular and Cellular Biology

STUDY_SECTION: TWD

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


ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Overall – Project Narrative Current HIV-1 therapy (HAART) can control but not cure HIV-1 infection. The overarching scientific theme of this Program is to discover and apply novel approaches and state-of-the-art technologies to protect, direct, and sustain anti-HIV T cell responses that can obviate the need for lifelong HAART in HIV-infected patients.

PI_NAMEs: RILEY, JAMES L. (contact)

PROGRAM_OFFICER_NAME: POON, BETTY

PROJECT_TERMS: Acceleration;Adoptive Transfer;Animal Model;antiretroviral therapy;B-Cell Acute Lymphoblastic Leukemia;bench to bedside;bioinformatics tool;BLT mice;cancer immunotherapy;CAR T cell therapy;CD19 gene;Cell Physiology;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;chronic infection;Clinic;Clinical Trials;Combination immunotherapy;Competence;Cost Sharing;CXCR4 gene;Data;detection limit;Discipline;Economic Burden;Elements;engineered T cells;Engineering;exhaustion;experience;FDA approved;functional improvement;Future;Genetic;Genome;Genome engineering;Goals;Hematologic Neoplasms;Highly Active Antiretroviral Therapy;HIV;HIV Infections;HIV resistance;HIV-1;Human;humanized mouse;Immune system;Immunotherapy;improved;In complete remission;Individual;Industry;Infection;Infusion procedures;inhibitor;Lead;Licensing;Lymph;Malignant Neoplasms;Mammals;manufacture;Mediating;Medical;medical schools;Modeling;mouse model;nonhuman primate;novel strategies;Pathway interactions;Patients;Pattern;Phase I Clinical Trials;Process;process improvement;programs;Refractory;Research;Research Personnel;Resistance;Resources;Safety;Screening procedure;success;synergism;T cell response;T-Lymphocyte;Technology;Testing;Therapeutic;tissue resident memory T cell;Tissues;tool;trafficking;Translating;Translations;Virus Replication

PROJECT_TITLE: Engineering T cells to Provide Durable Control of HIV-1 Replication


PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adherence;Administrator;Advisory Committees;Annual Reports;antiretroviral therapy;Award;Basic Science;bench to bedside;Biometry;BLT mice;Budgets;CAR T cell therapy;Clinical;clinical center;clinical epidemiology;clinical trial implementation;Clinical Trials;Communication;data management;data sharing;design;engineered T cells;Ensure;experience;Genome;Goals;Guidelines;HIV;HIV-1;Home;Human Resources;Immunology;Individual;innovation;Laboratories;Logistics;manufacturing process;meeting reports;meetings;Mission;Modeling;Modification;Monitor;National Institute of Allergy and Infectious Disease;novel strategies;Occupational activity of managing finances;Outcome;Pharmacologic Substance;Phase I Clinical Trials;preclinical evaluation;Preparation;Principal Investigator;Private Sector;Productivity;programs;Progress Reports;Publications;Reporting;Research;Research Personnel;Resource Allocation;Scientist;Structure;T cell response;T-Lymphocyte;targeted nucleases;Testing;Therapeutic;timeline;tool;trafficking;United States National Institutes of Health;Viral reservoir;Work;working group

PROJECT_TITLE: Core A: Administrative


PI_NAMEs: BUSHMAN, FREDERIC D (contact)

PROJECT_TERMS: Adverse event;Aliquot;Behavior;beta Thalassemia;Categories;cell growth;Cell Physiology;Cells;cellular transduction;Chromosomal translocation;Clinical;clinical efficacy;Clonal Expansion;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Data;design;DNA;engineered T cells;Event;Evolution;experience;experimental study;Frequencies;Gene Modified;gene therapy;Gene therapy trial;Genes;Genetic;Genetic Transcription;Genome;Genome engineering;Genome-wide Unbiased Identification of DSBs Enabled by sequencing;Genomics;genotoxicity;Growth;HIV;HIV-1;HMGA2 gene;Human;Human Genome;human subject;IL2RG gene;Immunotherapy;improved;Infusion procedures;Insertional Mutagenesis;integration site;lentiviral integration;Lentivirus Vector;Methods;Modification;Molecular;Monitor;Nature;nuclease;Outcome;Pathway interactions;Patients;Procedures;Protocols documentation;Reagent;Recurrence;Safety;safety assessment;Site;Specificity;T-Cell Proliferation;T-Lymphocyte;targeted nucleases;Technology;Therapeutic;Therapeutic Effect;Time;vector

PROJECT_TITLE: Core B: Genome Engineering Core


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;HIV/AIDS;Immunotherapy;Infectious Diseases;Regenerative Medicine

PI_NAMEs: WHERRY, E. JOHN (contact)

PROJECT_TERMS: Adoptive Cell Transfers;bench to bedside;Bone Marrow;Bone Marrow Transplantation;cancer immunotherapy;Cancer Patient;CAR T cell therapy;CCR5 gene;Cell Physiology;Cell Therapy;chimeric antigen receptor T cells;Chronic;chronic infection;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR screen;Data;data integration;Effectiveness;engineered T cells;Engineering;exhaustion;experience;Failure;functional improvement;Future;Genes;Genetic Engineering;genome editing;Genome engineering;Genomics;Goals;Hepatitis B Virus;Hepatitis C virus;HIV;HIV Infections;HIV therapy;HIV-1;Homing;humanized mouse;IL7R gene;Immune;Immunologics;Immunotherapy;improved;in vivo;in vivo evaluation;Infection;interest;leukemia;Lymphocytic choriomeningitis virus;Malaria;Malignant Neoplasms;Memory;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Mutation;next generation;novel;Pathway interactions;Patients;pharmacologic;prevent;programmed cell death protein 1;Property;Research;Research Personnel;response;screening;success;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapy trial;Viral Load result;Virus Diseases

PROJECT_TITLE: Engineering HIV-specific T cells that have improved function and persistence


NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Nutrition;Obesity;Prevention;Women's Health Research

ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE  We have identified a novel marker of inflammation in the fatty tissue of the breast, which are crown-like structures that can be detected in surgical pathology specimens, and this measure of breast white adipose tissue inflammation (B-WATi) is associated with obesity and dysregulated metabolic factors. In the Pathways Study, a prospective cohort study of women diagnosed with invasive breast cancer in Kaiser Permanente Northern California, we will identify factors that influence B-WATi presence and severity, and determine whether B-WATi is associated breast cancer recurrence and survival. This project brings together ground- breaking and innovative work on B-WATi with the outstanding resources of the Pathways Study, and has the potential to identify actionable and modifiable risk factors to improve breast cancer outcomes.

PI_NAMEs: IYENGAR, NEIL MUKUND;KUSHI, LAWRENCE H (contact)

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: abdominal CT;Adipocytes;Adipose tissue;Affect;Alcohol consumption;Anabolism;Aromatase;biobank;Biological Assay;Biological Markers;Blood specimen;Body Composition;Body mass index;Body Size;Breast;breast cancer diagnosis;Breast Cancer Prognostic Factor;breast cancer progression;Breast Cancer Risk Factor;Breast Cancer Treatment;California;cancer diagnosis;cancer epidemiology;Cancer Prognosis;cancer recurrence;cancer surgery;cancer survival;carcinogenesis;Cessation of life;Characteristics;Clinical;clinical care;cohort;Crowns;cytokine;Data;density;Development;Diagnosis;Diagnostic;Diet;Dietary Practices;Disease;Disease Management;Drug or chemical Tissue Distribution;Dyslipidemias;Electronic Health Record;Enrollment;Enzymes;estrogenic;Estrogens;ethnic diversity;Ethnic Origin;Etiology;Exhibits;Female;Formalin;Funding;Grant;high risk;Hormone Receptor;Image;improved;Incidence;Inflammation;Inflammatory;inflammatory marker;Infrastructure;innovation;insight;Insulin Resistance;Investigation;Learning;lifestyle factors;Macrophage;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Gland Parenchyma;Mastectomy;Measures;Mediating;member;Metabolic;Metabolic dysfunction;Metabolic Marker;metabolic profile;Metabolic syndrome;Metabolism;modifiable risk;mortality;novel;novel marker;Obesity;Outcome;Paraffin Embedding;Participant;Pathway interactions;Patient-Focused Outcomes;Patients;Physical activity;Plasma;Population Heterogeneity;Postmenopause;Prevalence;Prognostic Factor;Prospective, cohort study;Race;racial diversity;Recurrence;Reporting;Resources;Risk Factors;Sampling;Scanning;Second Primary Cancers;Severities;Slide;Smoking History;Smoking Status;Specimen;Structure;subcutaneous;Surgical Pathology;systemic inflammatory response;Time;Tissue Embedding;Tissues;Visceral;Weight;Woman;women's diagnosis;Women's study;Work;X-Ray Computed Tomography

PROJECT_TITLE: Breast White Adipose Tissue Inflammation and Breast Cancer Outcomes

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


ORG_CITY: MINNEAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PUBLIC HEALTH RELEVANCE The broad objective of the Overall Program is to develop ready-made, off-the-shelf, allogeneic immune effector cells with precise targeting of tumor associated antigens without risks of effector cell exhaustion or on- target/off-tumor and other adverse effects. To accomplish this goal, we will engineer regulatory T cells and NK cells for better tumor targeting, extended in vivo persistence and anti-tumor potency with the potential for production at an industrial scale.

PI_NAMEs: WAGNER, JOHN E. (contact)

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Acute Lymphocytic Leukemia;Address;Adoptive Immunotherapy;Adoptive Transfer;Adverse effects;Affinity;Allogenic;Antibodies;Antigens;Antitumor Response;B-Cell Acute Lymphoblastic Leukemia;Binding;Biological Models;cancer immunotherapy;CD19 gene;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Therapy;Cells;cellular engineering;Cellular immunotherapy;chemoradiation;chemotherapy;Child;chimeric antigen receptor;chimeric antigen receptor T cells;clinical translation;clinical trial implementation;Clinical Trials;combinatorial;Communication;cost;Coupled;cytokine;cytokine release syndrome;Cytolysis;Data;design;Development;Dose;drug development;Drug Kinetics;Effector Cell;engineered NK cell;Engineering;exhaustion;experience;fitness;Funding;Genes;Genetic Engineering;Goals;Grant;Granzyme;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;Immune;Immunologic Monitoring;Immunotherapeutic agent;improved;in vivo;induced pluripotent stem cell;Industrialization;Inflammatory;Ink;Interleukin-15;interleukin-15 receptor;Intervention Studies;laboratory experiment;Lentivirus;leukemia;Ligands;Logistics;Lymphocyte Subset;Malignant Neoplasms;manufacture;manufacturing run;Mediating;Medicine;Membrane;Methods;Molecular Analysis;nanobodies;Natural Killer Cell Immunotherapy;Natural Killer Cells;neoplastic cell;Neurologic;novel;Pathway interactions;Patients;perforin;Pharmaceutical Preparations;Pharmacodynamics;Population;Pre-Clinical Model;Production;programs;Proliferating;public health relevance;Publications;Quality Control;receptor;Receptor Activation;Refractory Disease;Regulatory T-Lymphocyte;Remission Induction;Research;Research Personnel;response;Risk;Role;Safety;Salvage Therapy;Services;side effect;Signal Transduction;Solid Neoplasm;Source;Specificity;Statistical Data Interpretation;Surface;synergism;synthetic biology;T-Lymphocyte;Technology;Testing;Time;Toxic effect;Translations;treatment planning;trispecific killer engager;tumor;Tumor Antigens;Tumor Escape;tumor-immune system interactions

PROJECT_TITLE: Off-the-Shelf Immune Effector Cells for Hematological Malignancies


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Physical Activity;Prevention

ORG_CITY: Columbus

ORG_DEPT: PSYCHOLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Reductions in cardiorespiratory fitness, mobility, and muscle strength/power have been linked to poor cognitive performance and increased risk for dementia. The precise relationships among these physical attributes and various aspects of cognition, such as memory, planning, and inhibition, are unknown, thereby precluding the development of an optimal lifestyle approach to maintain cognitive functions with aging. Given the continued absence of a pharmacological cure for Alzheimer’s disease, the primary goal of the current study it to identify which modifiable physical attributes are most strongly linked to memory and brain health, with a long-term goal of mitigating cognitive decline and thereby increasing high quality-of-life years among older adults prior to mortality.

PI_NAMEs: HAYES, SCOTT M (contact)

PROJECT_TERMS: Acceleration;Adult;Age;age acceleration;age related;Aging;aging brain;aging population;Alzheimer's Disease;Attenuated;Brain;brain health;Brain region;cardiorespiratory fitness;Cognition;Cognitive;cognitive ability;Cognitive aging;cognitive function;cognitive performance;Data;dementia risk;Development;Diffusion Magnetic Resonance Imaging;Episodic memory;executive function;Exercise;exercise intervention;exercise program;Exhibits;Failure;Functional Magnetic Resonance Imaging;Future;Goals;Impaired cognition;improved;Individual;Intervention Studies;Intervention Trial;Knowledge;Life Style;lifestyle intervention;Link;Magnetic Resonance Imaging;Maintenance;Mediating;Memory;middle age;Mission;Mobility decline;Modeling;mortality;Motor;motor control;muscle strength;Musculoskeletal;National Institute on Aging;neural;neural network;older adult;Outcome;Performance;pharmacologic;Physical Performance;polygenic risk score;precision medicine;Quality of life;resistance exercise;Structure;System;Testing;Thick;white matter;Work

PROJECT_TITLE: Contributions of modifiable physical attributes to cognitive and brain aging

STUDY_SECTION: CP

STUDY_SECTION_NAME: Cognition and Perception Study Section[CP]


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Hematology;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

PHR: PUBLIC HEALTH RELEVANCE The broad objective of Project 1 is to develop a safe and potent off-the-shelf cell therapy. To accomplish this, we are proposing an alternative immune effector cell vehicle, specifically Regulatory T Cells (Treg) as they are capable of suppressing the release of inflammatory factors and host mediated immune rejection, and are amenable to industrial scale expansion, and additional engineering to enhance function, persistence and tumor killing with reduced risk of side effects.

PROJECT_TERMS: Acute Lymphocytic Leukemia;Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Adverse effects;Allogenic;Antibodies;Antigens;Autologous;B lymphoid malignancy;B-Cell Acute Lymphoblastic Leukemia;CAR T cell therapy;CD19 gene;CD8B1 gene;Cell Therapy;Cells;Characteristics;chemotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;chronic inflammatory disease;Clinical Trials;Complement;cytokine;cytokine release syndrome;cytotoxicity;Data;Development;Dose;Drug Kinetics;Economics;Effectiveness;Effector Cell;Engineering;exhaustion;Failure;FDA approved;first-in-human;Funding;Future;Genetic Engineering;Geography;graft vs host disease;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;Immune;Immunologic Receptors;improved;In Vitro;in vivo;Industrialization;Inflammatory;Interleukin 2 Receptor;Interleukin-2;large scale production;Logistics;Malignant Neoplasms;manufacture;Maximum Tolerated Dose;Mediating;Myeloid Progenitor Cells;nanobodies;Neurotoxicity Syndromes;novel strategies;Organ;Patients;peripheral tolerance;Persons;Pharmaceutical Preparations;Phase;Phase I/II Trial;potency testing;pre-clinical;Pre-Clinical Model;prevent;Prevention trial;Production;Proliferating;public health relevance;Refractory;Regulatory T-Lymphocyte;Relapse;research clinical testing;Resistance;Risk;Safety;safety testing;Salvage Therapy;side effect;Signal Transduction;Solid;System;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Toxic effect;tumor;Tumor Antigens

PROJECT_TITLE: Engineered CD4 Tregs Targeting B-ALL and AML


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Nanotechnology;Prostate Cancer;Urologic Diseases

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative  Sphingolipid metabolites are critical lipid-derived second messengers for oncogenesis and several sphingolipid-based therapeutics have shown great promise as cancer therapeutics. This research focuses on the regulation of sphingolipid metabolism by the androgen receptor and the use of ceramide nanoliposomes (CNL) as a novel therapeutic for prostate cancer patients. Moreover, the synergistic dynamics between epigenetics and lipid biology will be studied in tumors to uncover new therapeutic targets.

PI_NAMEs: DA COSTA PINHEIRO, PEDRO FILIPE  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: abiraterone;Ablation;Acetates;advanced prostate cancer;Agonist;Anabolism;Androgen Antagonists;androgen deprivation therapy;androgen independent prostate cancer;Androgen Metabolism;Androgen Receptor;Androgens;Animals;anti-cancer therapeutic;Area;Award;Big Data;Binding;bioinformatics tool;Biology;bisulfite sequencing;cancer cell;cancer diagnosis;Cancer Patient;career;Cell Death;Cell Death Induction;Cell Line;Cells;Ceramides;Cessation of life;ChIP-seq;chromatin immunoprecipitation;Combined Modality Therapy;Data;Development;Differentiation and Growth;Dihydrosphingosine;Disease;Disease Progression;Drug Targeting;Enzymes;Epigenetic Process;epigenome;Evaluation;FDA approved;field study;Future;Generations;Genetic Transcription;Gland;Goals;Grant;Growth and Development function;Hi-C;Hormonal;Hormone Responsive;hormone therapy;Hormones;improved;in vitro Model;Institution;Knockout Mice;Knowledge;Laboratories;Laboratory Research;Link;lipid metabolism;Lipids;Liposomes;LNCaP;male;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;men;Messenger RNA;Metabolism;Modality;Modeling;Molecular;mouse model;nanoliposome;new therapeutic target;Newly Diagnosed;novel;novel therapeutics;Nuclear Hormone Receptors;organ growth;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Play;Population;Postdoctoral Fellow;posttranscriptional;Pre-Clinical Model;Predisposition;promoter;Prostate;prostate cancer cell;prostate cancer model;Proteins;PTEN gene;Publishing;receptor binding;Receptor Signaling;Regulation;relapse patients;Research;Research Personnel;Research Project Grants;Role;Second Messenger Systems;Signal Pathway;skills;Sphingolipids;targeted treatment;Testosterone;Therapeutic;therapeutic target;Transcriptional Regulation;transcriptome sequencing;translational potential;tumor;Tumor Burden;tumor progression;tumorigenesis;virtual;whole genome;Work;Xenograft procedure

PROJECT_TITLE: Ceramide NanoLiposomes as a novel therapeutic for prostate cancer


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;HIV/AIDS;Human Fetal Tissue;Immunotherapy;Infectious Diseases

PROJECT_TERMS: antiretroviral therapy;B-Lymphocytes;Binding;BLR1 gene;BLT mice;cancer cell;Cardiovascular Diseases;CD19 gene;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;clinical efficacy;Combination immunotherapy;cost;Data;design;Drug or chemical Tissue Distribution;Effectiveness;engineered T cells;exhaustion;Frequencies;Functional disorder;Generations;genomic locus;Goals;HIV;HIV Antigens;HIV Infections;HIV-1;humanized mouse;Immune;immune activation;Immune system;Immunity;Immunotherapeutic agent;Immunotherapy;improved;in vivo;Individual;Infection;Inflammation;inhibitor;insight;integration site;interest;Interruption;latent HIV reservoir;Ligands;Malignant Neoplasms;manufacture;Modeling;Modification;Morbidity - disease rate;mortality;mouse model;Mutation;next generation;novel;novel strategies;Patients;Phase I Clinical Trials;prevent;programmed cell death protein 1;Resistance;Shock;Signal Transduction;success;synergism;T-Lymphocyte;Testing;tool;trafficking;Transforming Growth Factor beta;tumor;viral rebound

PROJECT_TITLE: Modeling Combination Immunotherapy for HIV Cure in Humanized Mouse Models


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;HIV/AIDS;Immunotherapy;Infectious Diseases

PI_NAMEs: COUGHLIN, CHRISTINA M (contact)

PROJECT_TERMS: Address;Adoptive Transfer;adverse outcome;Anniversary;Autologous;B-Cell Neoplasm;Basic Science;Biological Assay;CAR T cell therapy;CD19 gene;cell bank;Cell Physiology;Cell Therapy;Cellular immunotherapy;Childhood Acute Lymphocytic Leukemia;chimeric antigen receptor;chimeric antigen receptor T cells;Chronic Lymphocytic Leukemia;clinical center;clinical predictors;Clinical Trials;Clinical Trials Design;Collecting Cell;Correlative Study;Data;design;Disease;Disease remission;Employee;engineered T cells;Engraftment;Enrollment;experience;FDA approved;Gene Modified;gene therapy;Goals;Healthcare;Hematologic Neoplasms;Highly Active Antiretroviral Therapy;HIV;HIV Infections;HIV therapy;HIV-1;improved;improved outcome;Incentives;Individual;Industry;Infection;Infrastructure;insight;integration site;Interruption;Intervention;Investments;Knowledge;large scale production;Learning;Letters;Logistics;Malignant Neoplasms;manufacture;manufacturing cost;manufacturing facility;manufacturing process;Medicine;member;Methods;Modality;novel;novel therapeutics;Oncology;Outcome;Patients;Pennsylvania;Persons;Phase I Clinical Trials;Positioning Attribute;prevent;Process;programs;Protocols documentation;Qualifying;Refractory;Regimen;Relapse;Resistance;Rewards;Sampling;Specificity;Structure;T cell therapy;T-Lymphocyte;Technology;Testing;Therapeutic;Time;United States National Institutes of Health;Universities;vector;viral rebound;Work

PROJECT_TITLE: Clinical Trials Engine to Develop an HIV Cure study to test engineered T cells


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular

ORG_CITY: HOUSTON

ORG_DEPT: SURGERY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: NARRATIVE Cardiovascular diseases include some of the major causes of death in the United States population: heart attacks, heart failure, strokes, and aneurysms. Many of these illnesses can be prevented or managed with surgery. Training investigators in surgical cardiovascular research is essential to ensure that people receive the best possible care for these conditions.

PI_NAMEs: ROSENGART, TODD K (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: Cardiovascular Surgical Procedures;Research Training;Training Programs

PROJECT_TITLE: Research Training Program in Cardiovascular Surgery

STUDY_SECTION: NITM

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Gene Therapy;Genetics;Hematology;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Transplantation

PHR: Public Health Relevance Our goal is to develop new therapies for treating patients with relapse/refractory acute myelogenous leukemia (AML). This application proposes to tackle allogeneic hematopoietic cell (alloHCT) complications by using chimeric antigen receptor (CAR) Tlineage cells in a novel approach with unexpectedly potent cell type, induced regulatory T cells (iTregs) that has the dual capacity of preventing alloHCT side-effects and killing AML cells. Using drug regulated system to induce CAR expression for periods of time to restrain AML followed by rest periods to prevent T cells from being exhausted and dysfunction. This is accomplished by administration of a nontoxic drug to turn CAR expression on and stop drug to turn the system off in order to best treat AML, reducing toxicity and improving efficacy.

PI_NAMEs: BLAZAR, BRUCE R (contact)

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Adaptive Immune System;Address;Adoptive Transfer;Affect;Allogenic;Antigens;B lymphoid malignancy;Biological;Biological Assay;CD19 gene;CD4 Antigens;CD4 Positive T Lymphocytes;CD47 gene;CD8 receptor;CD8-Positive T-Lymphocytes;CD8B1 gene;cell killing;cell type;Cells;Cellular immunotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;clinical efficacy;cytotoxic CD8 T cells;Data;design;Development;differential expression;Dimerization;disorder control;Dose;Drug usage;Effector Cell;Ensure;Epigenetic Process;exhaust;exhaustion;Extracellular Domain;FOXP3 gene;Frequencies;Functional disorder;Generations;Genes;Genome;genome editing;Goals;graft vs host disease;graft vs leukemia effect;Hematologic Neoplasms;Hematopoiesis;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Human;human induced pluripotent stem cells;human pluripotent stem cell;humanized mouse;IL2 gene;Immune;Immune response;Immunologic Surveillance;Immunotherapeutic agent;improved;In Vitro;in vivo;induced pluripotent stem cell;Innate Immune System;Interleukin-6;ITAM;Knock-in;Lead;leukemia;leukemic stem cell;Libraries;Ligands;Longevity;Lymphoma;Lymphoma cell;Macrophage;Malignant - descriptor;Mediating;mouse model;Mus;Myeloid Cells;Myeloid Progenitor Cells;Myelosuppression;nanobodies;Non-Malignant;novel strategies;novel therapeutics;overexpression;patient derived xenograft model;Patients;Periodicals;peripheral blood;Pharmaceutical Preparations;prevent;Procedures;Productivity;promoter;Property;Proteins;public health relevance;receptor;receptor expression;Receptor Signaling;Refractory;Regulatory T-Lymphocyte;Relapse;Resistance;response;Rest;restraint;Risk;self-renewal;side effect;Signal Transduction;site-specific integration;STAT3 gene;stem cells;synergism;System;T cell response;T-Cell Activation;T-Cell Development;T-Cell Receptor;T-Lymphocyte;Testing;Thymus Gland;Time;Toxic effect;transcription factor;transcriptomics;Treg therapy;tumor

PROJECT_TITLE: "Off-the-Shelf" iPSC-Derived Regulatory T Cell Immunotherapeutics


ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: PROJECT NARRATIVE While antiretroviral therapy (ART) has achieved remarkable success, with AIDS patients now living long, full lives, HIV-1 infection remains incurable due to the presence of a persistent viral reservoir, capable of rebounding upon interruption of treatment. The RID-HIV (Reversing Immune Dysfunction for HIV-1 eradication) Collaboratory brings together leading university scientists from more than twelve academic institutions as well as Merck Research Laboratories, with the goal to understand the molecular and cellular basis for the loss of immune homeostasis in HIV infected patients. This knowledge will be harnessed to create a therapeutic paradigm encompassing immune restorative treatments, utilized in concert with enhanced viral reactivation and elimination strategies, to establish a HIV-1 cure.

PI_NAMEs: CANNON, PAULA M;CHANDA, SUMIT K (contact);SEKALY, RAFICK PIERRE

PROGRAM_OFFICER_NAME: SHANKAR, UDAY K

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;adaptive immune response;Address;Adult;Age;Allogenic;Anatomy;Antibodies;antiretroviral therapy;Automobile Driving;B-Lymphocytes;BCL1 Oncogene;Binding;Biology;Biomedical Research;CCR5 gene;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Physiology;Cell Therapy;Cells;Clinic;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Collaborations;collaboratory;Combined Modality Therapy;Communities;Community Outreach;Complement;Containment;design;Development;drug repurposing;Effector Cell;Engineering;Engraftment;Ensure;Epigenetic Process;experience;FDA approved;Feedback;FRAP1 gene;Future;Gene Modified;Genes;Genetic;Goals;gut microbiome;high risk;HIV;HIV Infections;HIV-1;HIV/AIDS;Homeostasis;Human;Immune;immune function;Immune response;immune restorative treatment;Immune system;Immune System Diseases;Immunology;Immunomodulators;imprint;improved outcome;in vivo;in vivo evaluation;Individual;Infection;Infrastructure;inhibitor;Innate Immune Response;innovation;Institution;Interruption;Intervention;Investments;Knowledge;Laboratory Research;latent HIV reservoir;Ligands;Maintenance;mathematical model;Mediating;member;Metabolic Control;metabolome;microbiome;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;Natural Immunity;Natural Killer Cells;neutralizing antibody;neutrophil;novel;novel strategies;novel therapeutic intervention;Outcome;Outcome Study;outreach;pandemic disease;Pathway interactions;Patients;pharmacologic;pre-clinical;preservation;prevent;Proviruses;Reagent;receptor;Recording of previous events;recruit;Research;Resources;Scientist;Shapes;stem;success;Systems Biology;T memory cell;T-Lymphocyte;Testing;Therapeutic;therapy adherence;Time;tool;Transforming Growth Factor beta;Translations;Tumor Debulking;Universities;Viral;viral rebound;Viral reservoir;virology;Virus;Virus Latency;Virus Replication;Voice;Work

PROJECT_TITLE: Reversing Immune Dysfunction for HIV-1 Eradication


NIH_SPENDING_CATS: Behavioral and Social Science;Breastfeeding, Lactation and Breast Milk;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Contraception/Reproduction;Cost Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Networking and Information Technology R&D (NITRD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Social Determinants of Health;Telehealth;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Postnatal care and support is critical for ensuring healthy mothers and infants, yet very few women receive any postnatal care in rural India. Maa Shishu Swasthya Sahayak Samooh (MeSSSSage) is a mobile platform developed by our team to provide group education and support about postpartum and infant health, including referral. We will evaluate the impact of MeSSSSage on exclusive breastfeeding, met need for family planning, and postpartum mental health, with the long-term goal of scaling up educational and support resources for mothers during a neglected period to optimize family health.

PI_NAMEs: DIAMOND-SMITH, NADIA GRIFFI;EL AYADI, ALISON M (contact)

PROGRAM_OFFICER_NAME: MITCHELL, MEGAN S

PROJECT_TERMS: acceptability and feasibility;Asian Women;Attention;Behavior;behavior change;care costs;care seeking;Caring;Community Health Aides;comparison intervention;Continuity of Patient Care;cost;Cost Analysis;cost effective;cost effectiveness;Cost Effectiveness Analysis;cost-effectiveness ratio;disparities in women;disparity reduction;Drops;Education;Effectiveness;effectiveness evaluation;Effectiveness of Interventions;effectiveness outcome;effectiveness testing;Ensure;Equation;evidence base;Excision;Exclusive Breastfeeding;Family health status;Family Planning;Geography;Goals;group intervention;Health;Health behavior;Health behavior and outcomes;health knowledge;Health Services Accessibility;improved;incremental cost-effectiveness;India;Infant;Infant Health;Infant Mortality;International;Intervention;Knowledge;Late pregnancy;Live Birth;Maternal and Child Health;Maternal Health;Maternal Mortality;maternal outcome;Mediation;Mental Health;Methods;mHealth;mobile computing;Modeling;Modernization;Mothers;neglect;neonatal health;neonatal outcome;Nurse Midwives;opportunity cost;Outcome;Pathway interactions;Patient Recruitments;peri-urban;Perinatal;Perinatal Care;perinatal health;perinatal women;Personal Satisfaction;Persons;Pilot Projects;pilot test;postnatal;Postnatal Care;postnatal period;postpartum care;postpartum contraception;Postpartum Depression;postpartum health;Postpartum Period;Postpartum Women;prenatal;primary outcome;Provider;provider communication;Randomized;Randomized, Controlled Trials;Research Personnel;Resources;Risk;Rural;rural area;rural dwellers;scale up;secondary outcome;Self Efficacy;social;social culture;Social Network;Social stratification;Social support;Social Values;sociodemographics;South Asian;standard care;standard of care;Support Groups;symposium;Testing;Text;urban area;virtual;Well in self;Woman;women's outcomes

PROJECT_TITLE: Effectiveness of an mHealth Interactive Education and Social Support Intervention for Improving Postnatal Health

STUDY_SECTION: HPC

STUDY_SECTION_NAME: Health Promotion in Communities Study Section[HPC]


NIH_SPENDING_CATS: Aging;Bioengineering

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative Aging is a key factor in many diseases, such as cancer, diabetes, and neurodegenerative diseases. This project aims at integrating computational modeling and innovative measurement technologies to understand the complexity of single-cell aging and the emergent dynamics from the underlying regulatory networks. Computational models developed from this project will advance a quantitative understanding of mechanisms underlying aging dynamics, laying foundations for strategies for mitigating age-related diseases.

PI_NAMEs: HAO, NAN  (contact);HASTY, JEFF M;PILLUS, LORRAINE ;TSIMRING, LEV S

PROGRAM_OFFICER_NAME: TSAP, LEONID V

PROJECT_TERMS: 5'-AMP-activated protein kinase;Affect;age related;age-related disease;Aging;aging process;aging related;Automobile Driving;Autophagocytosis;Biology of Aging;cell age;Cell Aging;Cells;Complex;Computer Models;Consumption;Data;Deacetylase;Development;Diabetes Mellitus;Disease;dynamic system;Environment;environmental change;Environmental Risk Factor;Equilibrium;Eukaryota;experimental study;extend lifespan;Foundations;functional decline;Funding;gene interaction;gene network;Genes;Genetic Engineering;Genetic Transcription;hallmarks of aging;healthspan;Heat-Shock Response;Heme;Homeostasis;Human;Imaging technology;Incidence;Individual;innovation;Intervention;life span;Longevity;Lysine;Malignant Neoplasms;Measurement;Mediating;Metabolic;Metabolism;Microfluidics;Mitochondria;model organism;Modeling;Molecular;Molecular Chaperones;multicatalytic endopeptidase complex;multidisciplinary;Neurodegenerative Disorders;Nutrient;Pathway interactions;Phenotype;population based;Process;Production;Property;protein aggregation;protein folding;Proteins;proteostasis;proteostasis loss;proteotoxicity;rate of aging;Regulation;Research;Ribosomal DNA;Role;Saccharomyces cerevisiae;sensor;Stochastic Processes;Stress;success;System;Systems Biology;Technology;Testing;Therapeutic Intervention;Yeasts

PROJECT_TITLE: Network-Driven Dynamics of Replicative Aging

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Health Services;Prevention;Women's Health Research

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: Project Narrative Accurate, routine screening reduces deaths among the 1-in-8 women who will get breast cancer in their lifetime. Contrast-enhanced MRI screening has tremendous potential to improve on mammography screening, but it is limited by cost, discomfort, and concerns over the risks and beneﬁts of annual gadolinium contrast injections. We propose to develop non-contrast-enhanced breast MRI screening approaches that are accurate, more comfort- able and avoid the need for intravenous gadolinium contrast, and study these approaches for screening women at high risk of developing breast cancer.

PI_NAMEs: DANIEL, BRUCE L;HARGREAVES, BRIAN ANDREW (contact)

PROGRAM_OFFICER_NAME: ZHANG, HUIMING

PROJECT_TERMS: 3-Dimensional;Abbreviations;Benefits and Risks;Biopsy;Breast;Breast Cancer Detection;Breast Cancer Risk Factor;breast lesion;Breast Magnetic Resonance Imaging;bulk motion;Cessation of life;Clinical;clinical practice;Collaborations;Cone;contrast enhanced;Contrast Media;cost;Data;density;design;Development;Diagnosis;Diagnostic;diagnostic accuracy;Diffusion;Diffusion Magnetic Resonance Imaging;Disease;Early treatment;Echo-Planar Imaging;experience;flexibility;follow-up;Gadolinium;Goals;Health;Heterogeneity;high risk;high risk population;High Risk Woman;Image;imaging approach;imaging capabilities;imaging detection;imaging modality;Improve Access;improved;Injections;innovation;International;Intravenous;Lesion;Lesion by Morphology;lifetime risk;Magnetic Resonance Imaging;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Gland Parenchyma;Mammographic screening;Mammography;Measurement;Measures;Methods;Morphology;mortality;Motion;novel;Observational Study;Oncologist;Operative Surgical Procedures;Pathologist;patient screening;Patients;Performance;Phase;Population;Positioning Attribute;Predictive Value;preservation;Printing;prospective;Protocols documentation;radiologist;Recommendation;reconstruction;Reporting;research clinical testing;Resolution;Resources;Risk;Roentgen Rays;Role;routine screening;Scanning;screening;screening guidelines;Sensitivity and Specificity;side effect;Site;Specificity;Speed;Techniques;Technology;Testing;Time;time use;Tissues;tumor;Universities;Variant;Water;Wisconsin;Woman;Work

PROJECT_TITLE: Abbreviated Non-Contrast-Enhanced MRI for Breast Cancer Screening

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Hematology;Immunization;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PHR: PUBLIC HEALTH RELEVANCE We have developed a novel off-the-shelf therapeutic (called FT538) using a triple gene modified induced pluripotent stem cell that can be differentiated and manufactured into hundreds of doses of highly active natural killer cells that can be targeted with antibodies or chimeric antigen receptors to treat acute myelogenous leukemia. We will test the best way to use this knowledge in first-in-human clinical trials with the goal of making the treatment off-the-shelf for easy and feasible export to the cancer community.

PI_NAMEs: MILLER, JEFFREY S. (contact)

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Address;Adoptive Cell Transfers;Adoptive Transfer;Adult Acute Myeloblastic Leukemia;Affinity;Allogenic;Antibodies;antibody-dependent cell cytotoxicity;Antibody-drug conjugates;Antigen Targeting;Antigens;Binding;blood product;Bone Marrow;CD34 gene;CD8-Positive T-Lymphocytes;Cell Count;Cell Line;Cell Survival;Cells;chemotherapy;chimeric antigen receptor;Clinical;Clinical Trials;Collaborations;combinatorial;Communities;conditioning;Cryopreservation;Development;Disease;Disease Progression;Disease remission;Dose;Effectiveness;Effector Cell;engineered NK cell;Engineering;Enrollment;exhaustion;Exhibits;experience;Exposure to;Fc Receptor;FCGR3B gene;FDA approved;first-in-human;Gene Modified;Generations;Genes;Genetic;Genome engineering;Goals;Hematologic Neoplasms;Hematopoietic;Hematopoietic Stem Cell Transplantation;Heterogeneity;human stem cells;Immune;immune reconstitution;Immunosuppressive Agents;Immunotherapy;improved;in vivo;induced pluripotent stem cell;Infusion procedures;Ink;insight;Interleukin-15;interleukin-15 receptor;Knock-out;Knowledge;leukemia treatment;leukemic stem cell;Malignant Neoplasms;manufacture;medical specialties;Membrane;Metabolism;Modeling;Modification;Monoclonal Antibodies;Myeloid Cells;Myelosuppression;Natural Killer Cell Immunotherapy;Natural Killer Cells;new therapeutic target;NK cell therapy;novel;novel strategies;overexpression;Oxidative Stress;patient derived xenograft model;Patients;peripheral blood;personalized approach;Phase I Clinical Trials;phase I trial;preclinical study;Prevention;Process;progenitor;programs;public health relevance;Refractory;Relapse;Remission Induction;Resistance;Role;Signal Transduction;Specificity;Suppressor-Effector T-Lymphocytes;synergism;System;T-Lymphocyte;Testing;Therapeutic;Toxic effect;transcription factor;Treatment Failure;trispecific killer engager;Work

PROJECT_TITLE: Off-the-shelf iPSC-Derived Natural Killer Cell Immunotherapies for AML


NIH_SPENDING_CATS: Cooley's Anemia;Genetics;Hematology;Orphan Drug;Rare Diseases;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_NAME: BOSTON MEDICAL CENTER

PHR: PROJECT NARRATIVE  Sickle cell disease and β-thalassemia are the most common inherited disorders in man and affect millions of people around the world. If it were possible to increase the amount of fetal hemoglobin (HbF), a hemoglobin type found primarily in babies in utero, in the blood of patients with both diseases this would ameliorate disease severity and might even help cure these diseases. Our proposed studies targeting a new pathway that we discovered to induce HbF in human primary erythroid progenitor cells would have the potential to lead to the development of a novel and safer inducer to therapeutically increase HbF in people with these severe hereditary diseases.

PI_NAMEs: CUI, SHUAIYING  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Adenovirus Infections;Adult;Adverse effects;Affect;Agonist;Anemia;beta Globin;beta Thalassemia;Binding;Biogenesis;Birth;Blood;Bone Marrow Cells;CD34 gene;Cell Differentiation process;Cell Proliferation;Cells;Characteristics;Clinical;Clinical Research;Data;Development;Disease;DNA Binding Domain;early phase clinical trial;Embryo;epsilon Globin;Erythrocytes;Erythroid;Erythroid Cells;Erythroid Progenitor Cells;Erythropoiesis;Fetal Hemoglobin;Fetus;Functional disorder;gamma Globin;Gene Expression;gene therapy;Genes;Genetic Diseases;Genetic Transcription;global health;Globin;Hematology;heme biosynthesis;Hemoglobin;Hemoglobin A;Hemoglobin concentration result;hemoglobin polymer;Hemolysis;Hemolytic Anemia;Hereditary Disease;Histologic;Homologous Gene;Human;hydroxyurea;in utero;In Vitro;in vivo;in vivo evaluation;induced pluripotent stem cell;iron metabolism;Knockout Mice;Laboratory Study;Lentivirus Infections;Life;Link;loss of function;man;Messenger RNA;Methods;Missense Mutation;Mitochondria;Modeling;Molecular;Molecular Target;Morbidity - disease rate;mortality;mouse model;Mus;novel;Organ;overexpression;Pathology;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;pharmacologic;polymerization;Polymers;Population;PPAR gamma;preclinical study;Preclinical Testing;prenatal therapy;prevent;Production;progenitor;promoter;receptor;Regulation;Regulator Genes;Repressor Proteins;Research;Severity of illness;Sickle Cell;Sickle Cell Anemia;Sickle Hemoglobin;sickle vasoocclusion;sickling;small molecule;small molecule therapeutics;standard of care;Structure;Thalassemia;Therapeutic;Therapeutic Effect;transcription factor;Up-Regulation

PROJECT_TITLE: Targeting PGC-1a for the treatment of sickle cell disease

STUDY_SECTION: HTBT

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


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Epilepsy;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: QUEENS

ORG_NAME: ST. JOHN'S UNIVERSITY

ORG_STATE: NY

PHR: RELEVANCE TO PUBLIC HEALTH Aggressive and invasive glioblastoma with very poor prognosis and high mortality rate remains a big healthcare challenge. Repurposing brain-permeable FDA-approved molecules can be a successful strategy for glioblastoma therapy. Our objective is to repurpose an FDA-approved antiepileptic drug stiripentol for glioblastoma via studying its mechanistic pharmacology, medicinal chemistry, and preclinical efficacy.

PI_NAMEs: DUKHANDE, VIKAS VASUDEO (contact)

PROGRAM_OFFICER_NAME: BASKIR, RUBIN SAM

PROJECT_TERMS: 5'-AMP-activated protein kinase;Age;analog;Animal Model;anti-cancer;anti-epileptic agents;Antioxidants;Biological;Biological Assay;Biological Availability;Blood - brain barrier anatomy;Brain;Brain Neoplasms;Brain region;Cancer Biology;cancer cell;cancer pharmacology;cancer therapy;Catabolism;Cell Cycle;Cell Death;Cell Proliferation;Cell Survival;Cells;Chemicals;Chemoresistance;chemotherapy;Chemotherapy and/or radiation;Child;Circulation;cytotoxicity;Death Rate;Development;Diagnosis;dravet syndrome;Drug Delivery Systems;drug repurposing;Drug resistance;Effectiveness;efficacy evaluation;Enzymes;Epigenetic Process;Epilepsy;Epithelium;Excision;experimental study;FDA approved;Formulation;gamma-Aminobutyric Acid;Gene Expression;Genus Hippocampus;Glioblastoma;Glioma;Glycogen;Glycogen Phosphorylase;Glycolysis;Goals;Grant;Healthcare;Hydrogen Bonding;Hydrophobicity;Immune;Immune Evasion;Immunohistochemistry;In Vitro;in vivo evaluation;in vivo Model;inhibitor;insight;Investigation;Lactate Dehydrogenase;Lead;lead candidate;Link;lipid metabolism;Malignant Epithelial Cell;Malignant Glioma;Malignant Neoplasms;Measures;Mesenchymal;Metabolic;metabolic abnormality assessment;Metabolic Pathway;Metabolism;metabolomics;Molecular;mortality;Mus;Mutation;Neoplasm Metastasis;novel;novel therapeutics;Nuclear;Nucleotide Biosynthesis;Oncogenes;Operative Surgical Procedures;overexpression;Pathway interactions;Pentosephosphate Pathway;Permeability;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Pharmacology;Pharmacology Study;Pharmacotherapy;Phosphotransferases;Physiological;pre-clinical;preclinical efficacy;Preclinical Testing;Prevalence;Primary Brain Neoplasms;Primary carcinoma of the liver cells;Prognosis;Proliferating;protein expression;Proteins;Public Health;Radiation therapy;Reporting;Research;Resistance;Safety;scaffold;screening;Signal Transduction;standard of care;Structure-Activity Relationship;Survival Rate;synergism;Tail;temozolomide;Testing;Therapeutic;therapeutic candidate;timeline;transcriptome sequencing;treatment strategy;tumor;tumor metabolism;tumor microenvironment;Tumor Suppressor Genes;Tumor Tissue;tumor xenograft;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Pharmacological and Chemical Approaches to Repurpose an Antiepileptic for Glioblastoma Treatment


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Clinical Research;Genetics;Infectious Diseases;Lung;Microbiome;Precision Medicine;Rare Diseases

PHR: Narrative Recently described molecular phenotypes of the acute respiratory distress syndrome (ARDS) have distinct clinical trajectories and differential responses to treatments in secondary analyses of randomized controlled trials, but the mechanisms underlying these differences are poorly understood. The research proposed in this K23 will use tracheal aspirate RNA sequencing to identify the cellular circuits driving dysregulated pulmonary inflammation, test for the differences in microbial communities, and study the evolution and resolution of ARDS in each molecular phenotype. These aims complement a training plan designed to prepare me to apply for an R01 grant to study the interaction of pulmonary and systemic inflammation in ARDS phenotypes as an independent investigator within 5 years.

PI_NAMEs: SARMA, AARTIK  (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Acute Respiratory Distress Syndrome;Airway Disease;aspirate;Automobile Driving;bioinformatics tool;Biological;biological adaptation to stress;Biological Markers;Biology;Candida;career development;Cell model;Cell Proliferation;Clinical;cohort;Complement;Complex;Computer Analysis;COVID-19 patient;COVID-19/ARDS;cytokine;Data;design;dimensional analysis;Disease;drug candidate;dysbiosis;Enterobacteriaceae;Epidemiologic Methods;Evolution;experience;Family;Foundations;fungus;Future;Gene Expression;Gene Expression Profiling;Genes;Genomic approach;Goals;Grant;Health Care Costs;high dimensionality;Immune;Inflammation;Inflammatory;insight;Interferons;Interleukin-1;Interleukin-4;Knowledge;large datasets;Learning;Liquid substance;Longitudinal Studies;Lower respiratory tract structure;Lung;Lung Diseases;lung injury;Macrophage;Mechanical ventilation;Medicine;Mentored Patient-Oriented Research Career Development Award;Mentorship;metatranscriptome;metatranscriptomics;Methods;microbial;microbial community;microbiome;molecular phenotype;Morbidity - disease rate;mortality;National Heart, Lung, and Blood Institute;novel;Pathway Analysis;Pathway interactions;Patient Recruitments;Patients;Phenotype;Plasma;polarized cell;Positive-Pressure Respiration;Pre-Clinical Model;Precision therapeutics;Pulmonary Inflammation;Randomized, Controlled Trials;repaired;Reporting;Research;Research Personnel;Resolution;respiratory microbiome;Respiratory System;response;Risk;Sampling;secondary analysis;Signal Transduction;Simvastatin;single-cell RNA sequencing;skill acquisition;skills;STAT6 gene;systemic inflammatory response;T-Cell Activation;T-Lymphocyte;Taxon;Testing;Time Series Analysis;Trachea;Training;transcriptome sequencing;transcriptomics;Transforming Growth Factor beta;Trauma patient;treatment response;Uncertainty;unsupervised clustering;ventilation;Virulence Factors

PROJECT_TITLE: Evolution and resolution of ARDS molecular phenotypes

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(OA)]


NIH_SPENDING_CATS: Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Human

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Bone grafting remains the preferred treatment for bone defects, but this practice is limited by donor site morbidity. Alternatively, we seek to develop therapies that exploit the bone-regenerating potential of a specific type of bone marrow-derived stem cells. Here, we propose studies to understand how blood vessels regulate these human stem cells' activity, paving the way to more rational therapeutic strategies in the regeneration of bone defects.

PI_NAMEs: MELERO-MARTIN, JUAN M (contact)

PROGRAM_OFFICER_NAME: CHEN, FAYE H

PROJECT_TERMS: Affect;arteriole;Autologous;Binding;Binding Sites;Biological Assay;Blood Vessels;bone;Bone Marrow;bone marrow mesenchymal stem cell;Bone Regeneration;bone repair;Bone Transplantation;ChIP-seq;Compressive Strength;CRISPR/Cas technology;Data;Defect;DNA Binding;Endothelial Cells;endothelial stem cell;Enhancers;Exposure to;Foundations;Gene Expression Profile;Gene Modified;Genomics;Goals;Harvest;Hematopoietic stem cells;Human;human induced pluripotent stem cells;human stem cells;IFNAR1 gene;Immune system;Immunocompetent;Immunodeficient Mouse;implantation;in vivo;in vivo Model;induced pluripotent stem cell;Interferon Type I;Interferons;JAK1 gene;KITLG gene;Knock-in;Knowledge;Ligands;Link;loss of function;Luciferases;Mediating;Mediator;Membrane;Messenger RNA;Molecular;Morbidity - disease rate;Mus;Nature;notch protein;Notch Signaling Pathway;Osteoblasts;Osteogenesis;osteogenic;overexpression;Pathway interactions;Patients;Physiologic Ossification;preservation;Procedures;promoter;Promoter Regions;Property;Protein Isoforms;Proto-Oncogene Protein c-kit;recruit;regeneration potential;Regenerative Medicine;Regulation;Reporter;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Site;Source;STAT1 gene;STAT2 gene;stem cell fate;stem cells;substantia spongiosa;Testing;Therapeutic;therapy development;Titrations;Transfection;Transgenic Mice;TYK2;United States;Xenograft Model

PROJECT_TITLE: Human endothelial cell regulation of ossification

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

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

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: Project Narrative This project aims to create a pathway for bioengineering undergraduates to analyze rural health systems, create engineered devices to address health disparities, and implement their designs to improve rural communities in Maine. The objectives of this proposal are consistent with the goals of NIH R25 education projects and will have a significant impact on public health by developing a curriculum to support students in innovative design for rural communities. The unique nature of this proposal is the integration of community networks in supporting engineering design for rural healthcare, leveraging the expertise of four partner institutions to support the students in authentic learning that will ensure commitment to the rural communities.

PI_NAMEs: GRINDLE, DANIEL  (contact)

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: Accidental Injury;Address;Biomedical Engineering;Businesses;Career Choice;Cause of Death;Cessation of life;Clinical;Collaborations;Communities;Community Networks;Country;design;Development;Devices;Disparity;disparity gap;Economics;Education;Education Projects;Educational Curriculum;Eligibility Determination;Engineering;engineering design;Ensure;Entrepreneurship;experience;Exposure to;Face;Future;Goals;health care disparity;Health care facility;health disparity;Health system;Healthcare;Healthcare Systems;Heart Diseases;Immersion;improved;innovation;Institution;interdisciplinary approach;Learning;Maine;Malignant Neoplasms;Medical Care Team;Medical center;Medical Students;Mentors;Mentorship;Modeling;Nature;Pathway interactions;Persons;Politics;Population;programs;prototype;Public Health;Residencies;Resources;Risk;Running;Rural;rural America;rural Americans;Rural Community;rural disparities;Rural Health;rural healthcare;Rural Hospitals;scaffold;stem;Stroke;Students;Technology;Testing;Time;undergraduate student;United States;United States National Institutes of Health;Universities;Work

PROJECT_TITLE: Team-based Design to Address Rural Disparities in Healthcare