NIH_SPENDING_CATS: Bioengineering;Congenital Structural Anomalies;Genetics;Neurosciences;Pediatric;Rare Diseases

PHR: The proposed research is relevant to public health, because it will provide a mechanistic understanding of how genetic mutations in Piezo proteins, which are known to sense mechanical stimuli and function as sensors of light mechanical touch, proprioception, lung inflation and arterial blood flow, are resulting in several poorly- understood human diseases. The proposal will also explore how Piezo proteins work mechanistically. This in return may provide very specific strategies for treating each of the associated diseases.

PI_NAMEs: GRANDL, JORG  (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Affect;Arthrogryposis;biophysical analysis;Blood flow;Blood Vessels;Breathing;C-terminal;Cells;Colorectal;crosslink;Cysteine;Dehydration;Detection;Diagnosis;Disease;Distal;DNA Sequence Alteration;Dysplasia;Electrophysiology (science);Engineering;Extracellular Domain;Frequencies;Goals;Gordon syndrome;Heart;Hemolytic Anemia;Human;human disease;innovation;insight;Ion Channel;Ions;Kinetics;Knowledge;Ligands;Light;Lung;Lymphatic;Marden-Walker syndrome;Measures;mechanical force;mechanical stimulus;Mechanics;mechanotransduction;Membrane;Microphthalmos;Molecular;Molecular Conformation;mutant;Mutation;Pathway interactions;Patients;Permeability;Physiological;Piezo 1 ion channel;Piezo 2 ion channel;Piezo ion channels;Point Mutation;polyposis;Probability;Proprioception;Proteins;Public Health;Recovery;Research;sensor;Sensory;Stimulus;stomatocytic anemia;Stretching;Structure;Symptoms;Testing;Time;Touch sensation;vibration;Visualization;voltage;Work

PROJECT_TITLE: Mechanisms of Disease associated with mechanically-activated Piezo ion channels

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Neurosciences

ORG_CITY: DURHAM

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_FIPS: US

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Narrative A revolution in neuroscience has been the ability to control nerve cells with light; this is made possible by using viruses to deliver special genes to the cells. Such “optogenetic” technologies were developed using rodents, but they remain unreliable in non-human primates, the best animal model for understanding the human brain. We aim to rigorously enhance, map, and validate the efficacy of new viral methods for controlling neurons in the visual system of the primate brain to benefit both basic research and gene therapies for visuomotor disorders.

PI_NAMEs: SOMMER, MARC A (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: adaptive immune response;Anatomy;Animal Model;Animals;Area;arm;Atlases;Basic Science;Behavior;Brain;Brain Diseases;brain disorder therapy;Capsid;cell type;Cells;Chronic;Complex;constitutive expression;Dedications;Dependovirus;Disease;effective therapy;efficacy evaluation;efficacy validation;Electrophysiology (science);Enzymes;FDA approved;frontal eye fields;Gene Expression;gene therapy;Genes;Genetic;Glycoproteins;Goals;Histologic;Human;Immune response;Immune system;Immunology;immunoregulation;improved;in vivo;in vivo evaluation;inhibitor;Injections;Innate Immune Response;insight;interest;Intervention;Lentivirus;Lentivirus Vector;Light;Macaca;Maps;Mediating;Methods;Modeling;Modernization;Molecular;Monkeys;neural;neural circuit;Neurobiology;neuronal circuitry;Neurons;neurophysiology;Neurosciences;nonhuman primate;novel therapeutics;oculomotor;Opsin;optogenetics;orbit muscle;Outcome;Output;Pattern;Pharmaceutical Preparations;pharmacologic;Physiological;Population Projection;prevent;Primates;promoter;Proteins;Protocols documentation;reagent testing;Recombinant adeno-associated virus (rAAV);recruit;Regimen;Research;retrograde transport;Rodent;Role;Sirolimus;Site;Specificity;success;superior colliculus Corpora quadrigemina;System;T-Lymphocyte;Techniques;Technology;therapeutic gene;tool;Topoisomerase;Topoisomerase Inhibitors;transgene delivery;transgene expression;Transgenes;Transportation;V1 neuron;Validation;vector;Viral;Viral Vector;virology;Virus;Vision;Vision research;Visual;visual control;visual map;visual motor;visual neuroscience;Visual System;Work

PROJECT_TITLE: Enhancement, mapping, and validation of viral vectors for primate optogenetics


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Lung;Orphan Drug;Patient Safety;Prevention;Rare Diseases;Regenerative Medicine;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: NARRATIVE Our primary goal is to delineate adverse long-term health outcomes after curative therapies in children and adults with sickle cell disease (SCD). Despite the recent success of curing sickle cell disease, there have been limited systematic efforts to elucidate long-term health outcomes. Ultimately, the shortened lifespan of young adults with SCD, attributable to declining heart, lung, and kidney function, for which curative therapies were designed to address, must be measured against favorable and unfavorable late outcomes (mortality and morbidity) of these therapies.

PI_NAMEs: DEBAUN, MICHAEL R. (contact);FITZHUGH, COURTNEY D;FRIEDMAN, DEBRA L.;PECKER, LYDIA

PROGRAM_OFFICER_NAME: DI FRONZO, NANCY L

PROJECT_TERMS: Academic Medical Centers;Acceleration;Address;Adult;adult stem cell transplantation;adverse outcome;Allogenic;Cessation of life;Child;Chimerism;clinical center;clinical risk;clinically significant;Clonal Evolution;cohort;Cohort Studies;curative treatments;Data;design;Disease;Enrollment;Family;Fertility;financial toxicity;follow-up;Functional disorder;Funding;gene therapy;Genes;genetic risk factor;Genotoxic Stress;Goals;Graft Rejection;Health;health related quality of life;Heart;heart function;Hematopoiesis;Hematopoietic Stem Cell Transplantation;Hospitals;immune reconstitution;improved;Incidence;Individual;Kidney;kidney dysfunction;Late Effects;Leadership;life span;Lung;Malignant Neoplasms;Measurement;Measures;Morbidity - disease rate;mortality;Myeloproliferative disease;National Heart, Lung, and Blood Institute;Organ;Outcome;Outcome Study;Pain;Patients;Pediatric Oncology;personalized approach;Positioning Attribute;Prevalence;Prospective cohort;Prospective, cohort study;Protocols documentation;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Registries;Renal function;Risk;Sickle Cell Anemia;sickling;success;survivorship;Testing;therapy outcome;Time;transplant centers;Transplantation;transplantation therapy;United States National Institutes of Health;young adult

PROJECT_TITLE: Clinical and genetic risk factors associated with adverse long-term health outcomes after curative therapies in individuals with sickle cell disease


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The goal of this proposal is to define the influenza-specific Fc-humoral profiles that associate with protection against influenza and the development of neutralizing antibody breadth to guide next generation design of a universal influenza vaccine.

PI_NAMEs: LINGWOOD, DANIEL  (contact)

PROGRAM_OFFICER_NAME: ARNOLD, MICHELLE MARIE

PROJECT_TERMS: Affinity;Antibodies;Antibody Affinity;Antibody Response;antibody-dependent cell cytotoxicity;Antibody-mediated protection;Antigen Presentation;Antigen-Antibody Complex;Antigen-Presenting Cells;Antigens;Automobile Driving;B-Lymphocytes;Binding;Biology;case control;Cells;Characteristics;cohort;Complement;Complement Activation;Complement Receptor;cytotoxicity;Data;Deposition;design;Development;Dissection;epidemiology study;Evolution;Failure;Fc Receptor;Future;global health;glycosylation;Goals;Hemagglutination;Human;Humoral Immunities;Immune;immune activation;Immunity;immunoregulation;Individual;Infection;Infection prevention;Inflammation;Influenza;influenza infection;influenza virus vaccine;innate immune function;Innate Immune System;insight;Link;Measures;Mediating;mouse model;Mus;Names;National Institute of Allergy and Infectious Disease;Natural Killer Cells;neutralizing antibody;next generation;novel;novel vaccines;pathogen;Phagocytes;Phagocytosis;Play;Reaction;recruit;Research;Role;Sampling;seasonal influenza;Seasons;Shapes;Structure of germinal center of lymph node;T-Lymphocyte;tool;universal influenza vaccine;Vaccination;Vaccine Design;vaccine development;vaccine response;vaccine strategy;vaccine-induced antibodies;vaccine-induced immunity;Vaccinee;Vaccines;Variant;Viral Physiology;Virus

PROJECT_TITLE: Defining the Fc-correlates of protection against influenza

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cancer;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Liver Cancer;Liver Disease;Organ Transplantation;Precision Medicine;Prevention;Rare Diseases;Transplantation

ORG_CITY: BALTIMORE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE The incidence of hepatocellular carcinoma (HCC) in the U.S. is increasing rapidly, faster than all but one solid cancer, but its prognosis remains dismal with a median survival less than one year. This project aims to investigate the use of blood, imaging, clinical biomarkers associated with rapid HCC progression and develop an accurate predictive algorithm for HCC prognosis. This will provide a more tailored approach to patient management and offer them effective therapy early.

PI_NAMEs: KIM, AMY K (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Algorithms;Asian Americans;biobank;Biological Markers;biomarker identification;Black Populations;Blood;Blood specimen;Blood Vessels;blood-based biomarker;Carcinoma;career;Cells;Cessation of life;Characteristics;circulating biomarkers;Cirrhosis;Clinical;clinical biomarkers;Clinical Data;clinical risk;Data;detection test;Deterioration;Development;Disease;Disease Progression;Early treatment;effective therapy;Eligibility Determination;end stage liver disease;Enrollment;Epidemiology;experience;Face;Functional Imaging;Genomics;Goals;Hepatitis C;Hispanic Populations;Hospitals;Image;Immune;improved;Incidence;Individual;individualized medicine;Instruction;Intervention;K-Series Research Career Programs;Laboratories;Link;liquid biopsy;Liver;Liver diseases;liver function;liver transplantation;Malignant Neoplasms;Measurement;Measures;Mentors;Metabolic syndrome;multidisciplinary;Natural History;Neoadjuvant Therapy;Neoplasm Circulating Cells;non-alcoholic fatty liver disease;novel;Obesity Epidemic;organ allocation;Outcome;outcome disparities;outcome prediction;patient population;Patient-Focused Outcomes;Patients;Performance;personalized approach;personalized medicine;Persons;Plasma;Positioning Attribute;prediction algorithm;predictive tools;Primary carcinoma of the liver cells;primary outcome;Prognosis;prognostic algorithm;Prognostic Factor;Prognostic Marker;prognostic value;prognostication;progression risk;prospective;radiological imaging;Research;Resources;Risk;Risk Factors;Role;Sampling;Scientist;Screening for cancer;secondary outcome;Serum;skills;Solid;Specimen;Staging;Techniques;Testing;Therapeutic;Time;Training;translational scientist;transplant centers;Transplant Recipients;Transplantation;treatment guidelines;treatment response;tumor;Tumor Burden;tumor DNA;tumor growth;tumor progression;Tumor Volume;Waiting Lists;Work

PROJECT_TITLE: Improved early prognostic algorithm for hepatocellulcar carcinoma

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


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

ORG_CITY: DAVIS

ORG_DEPT: UROLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: PROJECT NARRATIVE Increasing evidence showing that AKR1C3 and AR/ARv7 play important roles in promoting prostate cancer progression and resistance. We have developed a number of novel small molecules that function as dual inhibitors of AR/ARv7 and AKR1C3. This application is aimed to determine the efficacy, mechanisms of action, and safety of these small molecules and to develop as novel agents to treat advanced prostate cancer.

PI_NAMEs: GAO, ALLEN C. (contact);LI, PUI-KAI

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: abiraterone;advanced prostate cancer;Androgen Antagonists;Androgen Receptor;Androgens;Androstenedione;Anti-androgen Therapy;ATAC-seq;Automobile Driving;Biological Availability;Cancer Patient;Castration;Cell Count;cell growth;Cell Line;Cells;ChIP-seq;Chromatin;Chronic;Clinical;clinical development;Computer Models;CWR22Rv1;Data;design;Development;Dose;Drug Kinetics;Drug resistance;efficacy evaluation;enzalutamide;enzyme activity;Enzymes;Family;functional genomics;Future;Genes;genome-wide;Genomic approach;Goals;Growth;improved;In Vitro;in vivo;in vivo Model;inhibitor;Laboratories;Legal patent;Libraries;member;Metabolism;neoplastic cell;novel;novel strategies;novel therapeutics;Oxidoreductase;Pathway interactions;patient derived xenograft model;Patients;Play;Production;prostate cancer progression;Receptor Signaling;Resistance;Role;Safety;Signal Transduction;small molecule;Structure;targeted treatment;Technology;Testing;Testosterone;therapy resistant;Toxic effect;transcriptome;transcriptome sequencing;Translating;Treatment outcome;treatment response;tumor;tumor growth;tumor microenvironment;tumor progression;Variant;VCaP;Xenograft procedure

PROJECT_TITLE: Novel therapeutics dual targeting intracrine androgen synthesis and AR for advanced prostate cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Cannabinoid Research;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Physical Injury - Accidents and Adverse Effects;Prevention;Substance Misuse;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: ATLANTA

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: GEORGIA STATE UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE Sexual assault is a significant public health concern impacting 1 in 5 college women. Alcohol and cannabis are known risk factors for sexual assault victimization, and women who experience nonconsensual sex are at a greater risk of developing alcohol and cannabis use disorders. This project involves the development of a risk reduction program for high risk college women that will integrate evidence- and theory-based alcohol and cannabis prevention content into an evidence-based sexual assault risk reduction program.

PI_NAMEs: LEONE, RUSCHELLE MARIE (contact)

PROGRAM_OFFICER_NAME: FREEMAN, ROBERT

PROJECT_TERMS: Address;Age;aged;alcohol abuse therapy;Alcohol consumption;alcohol intervention;alcohol involvement;alcohol misuse;alcohol misuse prevention;alcohol myopia;alcohol use disorder;Alcohols;Applied Skills;Area;Assertiveness;Attention;Back;Behavioral;binge drinking;Cannabis;career;Clinical;clinical trial analysis;college;Control Groups;Cues;Data;Data Analyses;design;Development;drinking;Drug usage;Education;efficacy testing;emerging adult;empowerment;Evaluation;Event;evidence base;Evidence based intervention;Expectancy;experience;Female;fighting;Focus Groups;follow-up;Future;Goals;Grant;Health;high risk;Impaired cognition;Impairment;Individual;innovation;Intervention;K-Series Research Career Programs;marijuana use;marijuana use disorder;Mental Health;Mentored Research Scientist Development Award;Mentors;Mentorship;Methods;motor impairment;National Institute on Alcohol Abuse and Alcoholism;Online Systems;Outcome;Patient Self-Report;Perception;perpetrators;personalized normative feedback;Persons;Physicians;Play;post intervention;Prevention;Primary Prevention;programs;psychoeducation;Psychologist;Public Health;Qualitative Methods;Qualitative Research;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Recommendation;recruit;Reporting;Research;Research Activity;Research Methodology;Research Personnel;Research Project Grants;Research Training;Resistance;responsible research conduct;Risk;Risk Factors;risk perception;Risk Reduction;Role;Sampling;Scientist;sex;sexual assault;skill acquisition;skills;social norm;Strategic Planning;Survivors;Target Populations;Testing;theories;therapy development;Time;Training;Training Activity;United States National Institutes of Health;university student;usability;Victimization;web-based intervention;Woman;Writing

PROJECT_TITLE: Development of an Alcohol, Cannabis, and Sexual Assault Risk Reduction Program for High Risk College Women

STUDY_SECTION: AA

STUDY_SECTION_NAME: Epidemiology, Prevention and Behavior Research Study Section[AA-2]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: EAST LANSING

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: PROJECT NARRATIVE We have discovered that expression of a protein in the serine biosynthesis pathway, PHGDH, is associated with metastasis of triple negative breast cancer: low PHGDH drives production of the cancer-associated metabolite sialic acid and activates cellular programs that promote metastasis. Our project will investigate the links between PHGDH, sialic acid metabolism, and metastasis. This research will establish low PHGDH/high sialic acid as a biomarker of metastatic breast cancer and identify new strategies to treat this deadly disease.

PI_NAMEs: LUNT, SOPHIA  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Acetyl Coenzyme A;Affect;aggressive breast cancer;Anabolism;Automobile Driving;Biological Markers;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Patient;Carbon;Cell surface;Cells;Data;Development;Disease;Enzymes;experience;experimental study;Genes;Glycolysis;Glycolysis Pathway;Goals;inhibitor;Invaded;knock-down;Knock-out;Link;Malignant Breast Neoplasm;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Metabolic;Metabolic Control;Metabolic Pathway;Metabolism;metabolomics;Metastatic breast cancer;Methods;Michigan;Modeling;Molecular;mouse model;Neoplasm Metastasis;new therapeutic target;novel therapeutic intervention;overexpression;p38 Mitogen Activated Protein Kinase;Pathway interactions;Patients;Phenotype;Phosphoglycerate dehydrogenase;Phosphorylation;Positioning Attribute;Primary Neoplasm;Production;programs;Proliferating;protein expression;protein protein interaction;Proteins;Research;Resources;Risk;Role;Serine;Sialic Acids;sialylation;Specimen;SRC gene;Testing;transcription factor;triple-negative invasive breast carcinoma;tumor;Universities;Up-Regulation

PROJECT_TITLE: Examining PHGDH-mediated activation of sialic acid metabolism to drive triple-negative breast cancer metastasis

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;HIV/AIDS;Infectious Diseases;Lung;Lung Cancer;Prevention;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Despite the promise of smoking cessation interventions in people living with HIV (PLWH), intervention potential is limited by a lack of understanding about how to best implement evidence-based cessation strategies in this population. Tobacco treatment with first-line pharmacotherapy, delivered remotely in a proactive, opt-out fashion presents an opportunity for PLWH to receive robust, evidence-based tobacco treatment even if they are not currently motivated to quit smoking. By optimizing the delivery of effective tobacco treatments for PLWH, we hope to increase the number of people receiving tobacco treatment, increase tobacco cessation rates, and reduce the risk of morbidity and mortality from smoking-related causes.

PI_NAMEs: ROJEWSKI, ALANA  (contact)

PROGRAM_OFFICER_NAME: KAUFMAN, ANNETTE R

PROJECT_TERMS: Abstinence;Acquired Immunodeficiency Syndrome;Agreement;antiretroviral therapy;Area;Behavioral;Belief;Biochemical;Cancer Etiology;Caring;CD4 Lymphocyte Count;Cessation of life;Client satisfaction;Clinic;clinical care;Clinical Pathways;Communicable Diseases;Complex;Counseling;Country;Dissemination and Implementation;Effectiveness;effectiveness/implementation trial;Evaluation;evidence base;Evidence based intervention;follow-up;Future;future implementation;health care settings;Healthcare Systems;HIV;Hour;implementation evaluation;implementation facilitators;implementation fidelity;implementation outcomes;implementation process;implementation strategy;Incidence;Intervention;intervention delivery;Knowledge;Mail Order;Malignant neoplasm of lung;Measures;Medical;Methods;Morbidity - disease rate;mortality;motivational enhancement therapy;novel strategies;Outcome;outreach;Participant;Patient Compliance;patient engagement;patient population;Patients;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Population;Prevalence;prevent;Provider;randomized, clinical trials;remote delivery;Research;Risk Reduction;Safety;Smoke;Smoker;Smoking;smoking cessation;Smoking Cessation Intervention;Smoking Status;Specialist;success;systemic barrier;Tobacco;Tobacco use;Tobacco Use Cessation;Training;treatment as usual;treatment comparison;United States;uptake;varenicline;Viral Load result;Visit;Writing

PROJECT_TITLE: Optimizing Tobacco Treatment Delivery for People Living with HIV


ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: RELEVANCE:) Abnormalities in platelet number and/or function can cause life-threatening complications such as bleeding and thrombosis. This proposal will fill important gaps in our understanding of the molecular mechanisms regulating the production, the intravascular survival, and the hemostatic function of platelets. Successful completion of the proposed work should lead to improved diagnosis and management of inherited and acquired bleeding disorders, and to novel and more personalized approaches for the prevention of thrombotic complications such as heart attacks and deep vein thrombosis. )

PI_NAMEs: BERGMEIER, WOLFGANG  (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: Adhesions;Biochemical;Biological;Biological Assay;Biology;Biosensor;Blood;Blood Cells;Blood Coagulation Disorders;Blood Platelets;Blood Vessels;Bone Marrow;Cardiovascular system;Cells;Clinical Research;Deep Vein Thrombosis;Development;Diagnosis;Disease;Funding;Future;Goals;Grant;Guanosine Triphosphate Phosphohydrolases;Hemorrhage;Hemostatic Agents;Hemostatic function;Human;improved;In Vitro;Inflammation;Inherited;inhibitor;inter-individual variation;Life;Megakaryocytes;Molecular;Molecular Profiling;Monitor;Monomeric GTP-Binding Proteins;mouse model;Mus;Myocardial Infarction;National Heart, Lung, and Blood Institute;novel;novel strategies;optogenetics;Pathology;Pathway interactions;Peripheral;personalized approach;Phagocytes;Platelet Activation;Platelet Count measurement;platelet function;platelet homeostasis;podoplanin;preservation;Prevention approach;Process;Production;Proliferating;Regulation;rho;Risk;Role;shear stress;Signal Transduction;Thrombocytopenia;Thrombosis;thrombotic complications;tool;transfusion medicine;Venous Thrombosis;Work

PROJECT_TITLE: Small GTPases in the biology of platelets and megakaryocytes


ORG_CITY: WINSTON-SALEM

ORG_DEPT: SURGERY

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: Narrative Chemoresistance of intestinal peritoneal surface malignancies is a considerable clinical problem with lethal consequences to patients. In this project we will develop a tumor organoid-based drug testing platform that models the genomic clonal composition of tumors and clonal drug response toward the prediction of clinical drug efficacy in patients.

PI_NAMEs: MILLER, LANCE DAVID;VOTANOPOULOS, KONSTANTINOS  (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: 3-Dimensional;Abdomen;Adjuvant Chemotherapy;Anatomy;Antigens;Architecture;Biomedical Engineering;Biopsy;cancer cell;Cancer Patient;cancer type;Candidate Disease Gene;carcinogenesis;Cell Death;cell killing;Cell Physiology;Cell Survival;Cells;Characteristics;Chemoresistance;Chemosensitivity Assay;chemotherapeutic agent;chemotherapy;Clinical;clinical efficacy;Clinical Management;clinical predictive model;clinical predictors;Clinical Treatment;Clinical Trials Design;clinically actionable;Clonality;colon cancer cell line;Colon Carcinoma;Colorectal;CT26;Cytotoxic T-Lymphocytes;design;Devices;Disease Resistance;DNA Sequence Alteration;driver mutation;Drug Combinations;drug efficacy;Drug Interactions;Drug resistance;drug response prediction;Drug Screening;drug sensitivity;drug testing;Effector Cell;Evaluation;Exhibits;FDA approved;Foundations;gene function;Gene Mutation;Genes;Genomics;Genotype;Goals;guided inquiry;Heterogeneity;Homeostasis;Human;Hyperthermia;Immune;Immune checkpoint inhibitor;Immunocompetent;Immunological Models;Immunooncology;immunoregulation;In Situ;insight;Intestinal Diseases;Intestines;intraperitoneal therapy;Lesion;Lung Neoplasms;Malignant - descriptor;Malignant neoplasm of appendix;Malignant neoplasm of gastrointestinal tract;Malignant Neoplasms;MC38;Measures;Mediating;Melanoma;Mesothelioma;metastatic colorectal;Methods;Microfluidic Microchips;Microsatellite Instability;Modality;Modeling;mouse model;Mus;Mutate;Mutation;Neoplasm Metastasis;neoplastic cell;Non-Malignant;novel;Operative Surgical Procedures;Organoids;parity;Pathway interactions;patient response;Patients;Performance;Peritoneal;Pharmaceutical Preparations;Phenotype;Postoperative Period;Prediction of Response to Therapy;preservation;Relapse;Reporting;Research;Resistance;Resolution;response;Role;Sampling;Sarcoma;Selection for Treatments;Site;Surface;System;targeted exome sequencing;Testing;treatment response;tumor;Tumor Debulking;Validation;Variant;Work;Xenograft Model

PROJECT_TITLE: Tumor Organoid-Mediated Drug Testing and Clonality Analysis in Peritoneal Surface Disease of Intestinal Origin


ED_INST_TYPE: SCHOOLS OF PHARMACY

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;Dementia;Diabetes;Neurodegenerative;Neurosciences

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on identifying specific pathological changes that reduce insulin delivery to the brain and cause cognitive changes. This new knowledge is expected to not only facilitate the discovery of new drugs against Alzheimer’s disease, but also help repurpose existing drugs that were approved to treat other diseases, such as diabetes and stroke. The proposed research is relevant to the part of the NIH’s mission pertaining to reducing illness and enhancing health.

PI_NAMEs: KANDIMALLA, KARUNYA KUMAR (contact);LOWE, VAL JOHN

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Address;aging population;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid beta-Protein;APP-PS1;Automobile Driving;Autophagocytosis;Blood - brain barrier anatomy;Blood brain barrier dysfunction;blood-brain barrier disruption;blood-brain barrier function;Brain;brain parenchyma;candidate identification;cerebral microvasculature;cerebrovascular;Cerebrovascular Circulation;Clinical;cognitive change;combat;comparison control;Complex;Coupled;Data;db/db mouse;Defect;Development;Diabetes Mellitus;Disease;Down-Regulation;Early Onset Alzheimer Disease;Endocytosis;Endothelium;Epidemiology;Etiology;Exhibits;Exocytosis;Flow Cytometry;Goals;Health;Hemorrhage;High Fat Diet;Image;imaging modality;Impairment;inhibitor;innovation;Insulin;Insulin Receptor;Insulin Resistance;insulin signaling;Kinetics;Knowledge;Label;Metabolic;Methods;Mission;Modeling;Molecular;Monitor;monolayer;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutic intervention;novel therapeutics;Obesity;overexpression;Pathologic;Pathway interactions;Pharmaceutical Preparations;Phase;Physiological;Plasma;Protein Array;Public Health;receptor expression;Research;Signal Transduction;single photon emission computed tomography;SNAP receptor;Stroke;synergism;targeted treatment;Techniques;Testing;Total Internal Reflection Fluorescent;trafficking;transcytosis;United States National Institutes of Health;uptake;Western Blotting;Wild Type Mouse;Work;X-Ray Computed Tomography

PROJECT_TITLE: Amyloid beta peptides and type-2 diabetes sequelae synergistically inhibit insulin signaling and trafficking at the blood brain barrier

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Contraception/Reproduction;Infectious Diseases;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: PEDIATRICS

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: PROJECT NARRATIVE Immunotolerance is a key aspect of pregnancy maintenance, mediated by specialized inhibitory immune cells, such as natural killer cells, at the maternal-fetal interface. Yet, these specialized immune cell populations must also remain vigilant to invading placental pathogens, such as cytomegalovirus (CMV), the leading global infectious cause of birth defects and long-term neurologic deficits. Using a nonhuman primate pregnancy model that closely mirrors pregnancy and congenital CMV transmission in humans, this proposal will fill the gap in our understanding of the role of specialized immune cell populations at the maternal-fetal interface and accelerate progress towards effective immune-based strategies to prevent adverse pregnancy outcomes, such as preterm labor and congenital infections.

PI_NAMEs: KAUR, AMITINDER ;PERMAR, SALLIE R. (contact);REEVES, ROGER KEITH

PROGRAM_OFFICER_NAME: MAJJI, SAI PRASANNA

PROJECT_TERMS: Acceleration;adverse pregnancy outcome;Affect;Amniotic Fluid;Animals;Antibodies;Blood;Blood Cells;CD4 Positive T Lymphocytes;Cells;Chronic;Congenital Abnormality;congenital cytomegalovirus;congenital infection;Cytomegalovirus;Cytomegalovirus Infections;Decidua;Decidual Cell;design;Development;early pregnancy;effective therapy;embryo/fetus antigen;Endometrium;Equilibrium;Event;fetal;Fetal Development;fetal immunity;Fetal Tissues;Fetus;Fracture;Frequencies;Gestational Age;Harvest;Health;hearing loss risk;Human;Immune;immune function;Immune System Diseases;Immune Tolerance;Immunity;Immunocompetent;immunogenic;Immunologic Surveillance;Immunologics;Immunology;Impairment;in utero;in vivo;Inflammation;Inflammatory;Invaded;Investigation;Late pregnancy;Leukocytes;Macaca;Macaca mulatta;Maternal-Fetal Exchange;Mediating;Memory;Methods;Modeling;Monitor;Morbidity - disease rate;mortality;Natural Killer Cells;Neurologic;Neurologic Deficit;NK Cell Activation;nonhuman primate;novel therapeutics;pathogen;Peripheral;Physiology;Placenta;Play;Population;Pregnancy;Pregnancy Complications;Pregnancy loss;Pregnancy Maintenance;Pregnancy Outcome;pregnancy prevention;Pregnancy Trimesters;pregnant;premature;Premature Labor;prevent;Prevention;receptor;Regulation;Rhesus;Role;Sampling;Second Pregnancy Trimester;seropositive;Testing;Third Pregnancy Trimester;Tissues;tool;transmission process;trophoblast;Umbilical Cord Blood

PROJECT_TITLE: Role of maternal-fetal interface NK cells in pregnancy maintenance and congenital CMV transmission

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


NIH_SPENDING_CATS: Biotechnology;Gene Therapy;Genetics;Hematology;Orphan Drug;Pain Research;Rare Diseases;Regenerative Medicine;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

PHR: NARRATIVE This application investigates new strategies to treat sickle cell disease using two potentially transformative technologies for precision genetic manipulation, termed base editing and prime editing. Specifically, we will use these new tools to modify the genome of blood forming cells from affected individuals to either directly repair the sickle cell disease mutation or circumvent its damaging effects. If successful, our strategies will lead to a safe and effective cure for a devastating disorder that affects 100,000 Americans and millions worldwide.

PI_NAMEs: LIU, DAVID R;WEISS, MITCHELL J (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Acute Pain;Adenosine;Adult;Affect;Affinity;Alanine;Alleles;Allogenic;American;Amino Acids;Antisickling Agents;Architecture;Autologous;base editing;base editor;Base Pairing;Benign;beta Globin;Biochemical;Biological Assay;Blood;Caring;CD34 gene;Cell Death;Cell Line;Cell Physiology;Cell Therapy;Cells;Cessation of life;Chromosomal Rearrangement;chronic pain;Clinical Research;Codon Nucleotides;Complex;curative treatments;Deterioration;Development;Disease;DNA;DNA Double Strand Break;Elements;Engineering;Engraftment;Enzymes;Erythrocytes;Erythroid Cells;Erythroid Progenitor Cells;Escherichia coli;Evolution;experience;Fetal Hemoglobin;Frequencies;Functional disorder;Future;Gene Expression;Gene Silencing;gene therapy;Genes;Genetic;genetic approach;Genetic Diseases;Genetic Engineering;genetic information;genetic manipulation;Genetic Template;Genome;genome editing;Genomic DNA;Genomics;Germ Lines;Globin;Guide RNA;Hematological Disease;Hematopoietic;Hematopoietic Stem Cell Transplantation;Hematopoietic stem cells;Hemoglobin;Hemoglobin F Disease;Hemolytic Anemia;HLA Antigens;Human;Hypoxia;improved;In Vitro;in vivo;Individual;Inherited;insight;Maintenance;Malignant - descriptor;manufacture;Mediating;Medical;Messenger RNA;Methods;Missense Mutation;Modification;Morbidity - disease rate;mortality;mouse model;Multiple Organ Failure;Mus;mutant;Mutation;new technology;novel;novel strategies;Nucleotides;off-target mutation;Organ;Outcome;Pain;Patients;polymerization;Polymers;precision genetics;premature;prevent;prime editing;prime editor;promoter;Proteins;Quality of life;Reagent;Recombinants;Regulation;repaired;Research;RNA;Safety;safety testing;Sickle Cell;Sickle Cell Anemia;Sickle Cell Trait;sickle erythroid;Sickle Hemoglobin;sickling;Site;targeted treatment;Technology;Testing;Therapeutic;therapeutic target;tool;Toxic effect;Transcriptional Silencer Elements;Transplantation;Treatment Efficacy;Valine;Variant;Xenograft procedure

PROJECT_TITLE: Base editing and prime editing for sickle cell disease

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dementia;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Older adult smokers are at elevated risk for cognitive decline and Alzheimer’s disease and related dementias (ADRD) development and, unless they can successfully quit smoking, their prevalence will continue to rise. Unfortunately, older smokers are half as likely to attempt to quit smoking compared to younger adults, which may be a function of both dysfunctional beliefs/motivational deficits of older smokers and clinician inaction. The proposed work will develop and test a readily translatable Stage 1 motivational intervention for smoking cessation in older adults consisting of: (1) a novel patient-informed motivational message promoting smoking cessation, and (2) clear access routes to evidence-based smoking treatments (EBSTs) within a healthcare setting.

PI_NAMEs: JOHNSON, ADRIENNE L. (contact)

PROGRAM_OFFICER_NAME: RICE, ELISE

PROJECT_TERMS: Abstinence;Acceleration;Accounting;Address;African American population;Age;age-related disease;aging population;aging related;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;apprenticeship;Articulation;Belief;brain health;career development;Cause of Death;Cessation of life;Cholesterol;cigarette smoking;Clinical;Clinical Trials;Communities;comorbidity;cost;cost estimate;Counseling;Dementia;dementia risk;design;Development;Diabetes Mellitus;disability;Disease;dissemination science;Distress;Doctor of Philosophy;effective intervention;Effectiveness;Ensure;epidemiology study;Etiology;evidence base;experience;feasibility trial;Female;Fright;Future;Genetic Risk;Goals;Grant;Health;Health behavior change;health belief;health care settings;Health Professional;Healthcare Systems;healthy lifestyle;Heart Diseases;high risk;Hypertension;Impaired cognition;implementation framework;implementation science;improved;Incidence;Institute of Medicine (U.S.);Intervention;Life;Life Style Modification;Link;Literature;low socioeconomic status;Marketing;Medical;Mentors;Methodology;Modeling;modifiable risk;Motivation;motivational intervention;novel;older adult;Pathology;patient oriented;patient oriented research;Patients;Personal Satisfaction;Persons;Pharmacotherapy;Population;Prevalence;prevent;Prevention;primary care clinic;prospective;Psychologist;Public Health;public health priorities;Qualitative Methods;rapid growth;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Research;Research Personnel;Resources;Risk;Risk Factors;Route;Severities;Smoker;Smoking;smoking cessation;Smoking Cessation Intervention;Smoking treatment;Stroke;Subgroup;success;Survey Methodology;Surveys;symposium;Testing;therapy design;therapy development;Time;Tobacco Dependence;Training;Translations;treatment as usual;treatment comparison;Treatment Efficacy;Uncertainty;Underserved Population;Work;World Health Organization;young adult

PROJECT_TITLE: ADRD Prevention Messaging to Increase Smoking Cessation Attempts in Older Adult Smokers

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Behavior and Social Science of Aging Study Section[NIA-S]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Epilepsy;Neurodegenerative;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative The proposed research is relevant to public health because over 20 million people worldwide suffer from focal drug-resistant epilepsy and are potential candidates for cure with epilepsy surgical interventions. Upon successful completion of the proposed research, we expect our contribution to be development of noninvasive imaging biomarkers to predict IEEG functional dynamics and epilepsy surgical outcomes. Our findings may inform current and new therapies to map and alter seizure spread, and pave the way for less invasive, better- targeted, patient-specific interventions with improved surgical outcomes.

PI_NAMEs: DAVIS, KATHRYN ADAMIAK (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Ablation;Anatomy;Biological Markers;Biomedical Engineering;Brain;Brain region;Clinical;clinical care;Clinical Data;Collaborations;computational neuroscience;connectome;Coupling;Data;Development;Devices;Diagnostic tests;Diffusion Magnetic Resonance Imaging;Disease;Electrodes;Electroencephalography;Epilepsy;Evaluation;Functional Magnetic Resonance Imaging;Goals;Graph;Image;imaging biomarker;Imaging Device;Implant;implantation;improved;individual patient;innovation;Intervention;Intractable Epilepsy;Lasers;Lesion;Limbic System;Magnetic Resonance Imaging;Maps;Measures;Medical;Medicine;Methods;Morbidity - disease rate;multimodal data;Multimodal Imaging;Network-based;neuroimaging;neuroimaging marker;Neurology;neurosurgery;non-invasive imaging;novel;novel therapeutics;open source;Operative Surgical Procedures;Outcome;Partial Epilepsies;Patients;Pattern;Pennsylvania;personalized strategies;Persons;Pharmaceutical Preparations;predictive modeling;Procedures;professional atmosphere;Property;Public Health;Research;Resistance;Rest;Risk Reduction;Sampling;Sampling Errors;Seizures;South Carolina;spatiotemporal;Stereotyping;Structure;surgery outcome;Temporal Lobe;Temporal Lobe Epilepsy;Testing;Translating;United States;Universities;Work

PROJECT_TITLE: Optimized Intracranial EEG Targeting in Focal Epilepsy based upon Neuroimaging Connectomics

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Cardiovascular;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Infectious Diseases;Nutrition;Obesity;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Racial and Ethnic Minority Health Research

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative (Public Health Relevance) One of the most prominent clinical features of severe COVID-19 is exuberant inflammation and endothelial dysfunction. The proposed research investigates the effects of COVID-19 on cardiovascular function using deep phenotyping approaches including human endothelial cell gene expression profiling. These studies will provide the unique opportunity to investigate molecular underpinnings of long-term endothelial effects among patients with obesity and could have important preventive and therapeutic implications in understanding disease susceptibility to COVID-19.

PI_NAMEs: HAMBURG, NAOMI MIRIAM;HO, JENNIFER E (contact)

PROGRAM_OFFICER_NAME: KUNZ, JOHN FREDERIC

PROJECT_TERMS: 2019-nCoV;Acceleration;Acute;ADAMTS;Adverse effects;Age;Aging;Automobile Driving;Autopsy;Bioinformatics;Biology of Aging;Blood Vessels;Cardiac;cardiovascular effects;Cardiovascular Physiology;Cardiovascular system;Case/Control Studies;Cell Aging;Cells;Cessation of life;Clinical;Coronary;Coronavirus;COVID-19;COVID-19 impact;COVID-19 patient;COVID-19 sequelae;COVID-19 susceptibility;Critical Illness;Development;Disease;Disease susceptibility;Elements;Endothelial Cells;endothelial dysfunction;Endothelium;ethnic difference;ethnic minority population;Event;experience;Fibrin fragment D;Foundations;Future;gene complementation;Gene Expression;Gene Expression Profiling;Heart;high body mass index;high risk population;Human;Image;Individual;Inflammation;Inflammatory;insight;Insulin Resistance;Investigation;Kidney;Lead;Link;Longitudinal, observational study;Lung;Medical center;Metabolic dysfunction;Metformin;Microvascular Dysfunction;Minority Enrollment;Molecular;molecular phenotype;multidisciplinary;Nitric Oxide;Non obese;obese patients;obese person;Obesity;Obesity associated cardiovascular disease;Oxidative Stress;Participant;Pathway interactions;Patients;Peripheral;persistent symptom;Phenotype;Plasma;Positioning Attribute;Positron-Emission Tomography;post SARS-CoV-2 infection;Predisposition;Preventive;Production;prospective;Prospective Studies;Proteomics;public health relevance;racial difference;racial minority population;Recombinants;Recovery;Research;Research Personnel;response;SARS-CoV-2 infection;SARS-CoV-2 infection history;senescence;severe COVID-19;Severity of illness;sex;Symptoms;targeted treatment;Therapeutic;thrombotic;vascular bed;Vascular Diseases;Vascular Endothelium;Venous;Viral;Visceral;von Willebrand Factor

PROJECT_TITLE: Long-Term Endothelial Effects of COVID-19 in Obesity

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

ORG_CITY: ANN ARBOR

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Defective tracheal cartilage development leads to airway collapse during breathing, causing sudden death in infants. We will take the genetic and molecular approaches to characterize how BMP signaling is well- orchestrated in directing the tracheal cartilage development. The outcome of the proposed studies will establish the knowledge base for the practical therapeutic solutions.

PI_NAMEs: MISHINA, YUJI  (contact)

PROGRAM_OFFICER_NAME: NATARAJAN, ARUNA R

PROJECT_TERMS: Acute;Affect;Age;Airway Disease;Alternative Therapies;Animal Model;Attenuated;autosome;Bone Morphogenetic Proteins;Breathing;Cartilage;cartilage development;Child;chondrodysplasia;Chondrogenesis;Chronic;Cytoskeleton;Data;Death Rate;Defect;Development;Disease;Dose;Ensure;Erinaceidae;Esophagus;extracellular;Failure to Thrive;FBN1;FK506;Foundations;Functional disorder;gain of function;Genes;Genetic;Goals;Growth Factor;Healthcare;Impairment;Incidence;Individual;Infant Mortality;insight;Knowledge;knowledge base;Lead;Life;Ligands;loss of function;Mesenchymal;Mesenchyme;Modeling;Molecular;Mutant Strains Mice;Neonatal Mortality;novel;obstructive airway disease;Online Mendelian Inheritance In Man;Operative Surgical Procedures;Outcome;Pathologic;Patients;Pattern;pediatric patients;Perinatal mortality demographics;pharmacologic;Phenotype;Physical condensation;Play;prevent;Primitive foregut structure;Proteins;Regulation;Resources;Respiratory Failure;restoration;Role;Scheme;Shapes;Signaling Protein;smoothened signaling pathway;Structural defect;success;Sudden Death;Symptoms;Syndrome;Therapeutic;Therapeutic Intervention;Tissues;tool;Toxic effect;Trachea;Tracheal Epithelium;tracheomalacia;Tracheostomy procedure;Work

PROJECT_TITLE: Temporal regulation of BMP signaling in patterning the tracheal cartilage and pharmacological approaches to prevent tracheomalacia

STUDY_SECTION: LIRR

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Digestive Diseases;Immunization;Orphan Drug;Pancreatic Cancer;Prevention;Rare Diseases

ORG_CITY: OMAHA

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: PROJECT NARRATIVE This project proposes the synthesis of a near infrared dye conjugated to an antibody for mucin-16 to identify tumors in the pancreas and abdominal cavity. The targeted probes will be used to help guide surgical resections of these malignancies to improve pancreatic cancer treatment or, in the case of metastasis detection, prevent patients from non-beneficial surgery with high co-morbidities and start other treatments sooner.

PI_NAMEs: MOHS, AARON M. (contact)

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Abdominal Cavity;Address;advanced disease;Affinity;Anatomy;Antibodies;antibody conjugate;Autopsy;Binding;Biodistribution;Biological;Biological Markers;Blood;Cancer Etiology;cancer therapy;Cells;Cessation of life;Chemicals;Clinical;clinical application;clinical development;clinical translation;Clinical Trials;clinically significant;comorbidity;contrast enhanced;Contrast Media;cross reactivity;Curative Surgery;Data;Detection;Disease;Dose;Drug Kinetics;Early Diagnosis;Eligibility Determination;Evaluation;Excision;Fluorescence;fluorescence imaging;fluorescence-guided surgery;fluorophore;Goals;Greater sac of peritoneum;Heterogeneity;Human;human imaging;Image-Guided Surgery;imaging agent;imaging probe;imaging system;improved;In Vitro;in vivo;Injections;Investigation;Label;Laparoscopy;Lead;Ligands;Location;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Methods;Microscopic;Molecular Probes;Molecular Target;Morbidity - disease rate;Mucins;murine antibody;Mus;near infrared dye;Neoadjuvant Therapy;Neoplasm Metastasis;novel;Operative Surgical Procedures;optical imaging;Optics;Organ;overexpression;Pancreas;pancreatic cancer model;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Patients;Peritoneal;Persons;Pharmacologic Substance;pre-clinical;Pre-Clinical Model;preclinical development;preclinical study;prevent;Property;Recombinants;Recurrence;Recurrent disease;Research Project Grants;Resectable;Safety;Sampling;Signal Transduction;specific biomarkers;Specimen;statistics;Symptoms;System;Therapeutic;Tissues;Toxic effect;Toxicology;treatment optimization;treatment strategy;tumor;Unnecessary Surgery;Visualization;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Preclinical development of a novel antibody conjugate for intraoperative detection of pancreatic cancer

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biotechnology;Data Science;Machine Learning and Artificial Intelligence;Microbiome;Networking and Information Technology R&D (NITRD)

ORG_DEPT: PHYSICS

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: Project Narrative The overarching goal of the proposed research is to develop new theoretical and computational tools that can be combined with experiment to model emergent, system-level behaviors in biology. These tools will allow scientists to leverage the power of modern theory, computation, and advances in “artificial intelligence” to tackle fundamental problems relevant to human disease in the context of microbial ecology, systems biology, and synthetic biology.

PI_NAMEs: MEHTA, PANKAJ  (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Artificial Intelligence;Attention;Behavior;behavior prediction;Biochemical;Biological;Biological Models;Biological Phenomena;Biology;Cells;Communities;Community Networks;Complex;Computational algorithm;computerized tools;Data;deep learning;Dictyostelium discoideum;Discipline;Ecology;experimental study;explainable machine learning;gene interaction;gene network;Goals;heterogenous data;human disease;information model;information processing;Information Theory;interdisciplinary approach;Length;Machine Learning;machine learning algorithm;Mathematics;microbial;microbial community;microbiome;model organism;Modeling;Modernization;Muscle;Neurons;novel;Organism;Physics;Pythons;Research;Resources;Scientist;Series;Signal Transduction;Source;Statistical Algorithm;synthetic biology;System;Systems Biology;Techniques;theories;tool;Transcend;United States National Institutes of Health;Work

PROJECT_TITLE: MODELING EMERGENT BEHAVIORS IN SYSTEMS BIOLOGY: A BIOLOGICAL PHYSICS APPROACH

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biodefense and Related Countermeasures;Brain Disorders;Dementia;Emerging Infectious Diseases;Genetics;Infectious Diseases;Neurodegenerative;Neurosciences;Rare Diseases;Transmissible Spongiform Encephalopathy (TSE)

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative This R01 proposal pursues an original hypothesis that apoE expressed by astrocytes and that expressed by activated microglia exert oppositional control on the behavior of microglia in conformational neurodegenerative disorders like Alzheimer's disease and prionoses and examines therapeutic merit of apoE-based approaches.

PI_NAMEs: SADOWSKI, MARTIN JOSEPH (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: abeta accumulation;abeta deposition;Alleles;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid beta-Protein;Apolipoprotein E;Apolipoproteins;Astrocytes;ATP binding cassette transporter 1;Attenuated;Behavior;Behavior Control;Brain;brain control;Cells;Characteristics;chemokine;connectome;Cre-LoxP;Creutzfeldt-Jakob Syndrome;cytokine;Deposition;Disease;Event;Gene Expression;Genes;Genotype;Grant;High Density Lipoproteins;high risk;Homeostasis;Homozygote;Human;Impairment;Incubated;Inflammation;Inflammatory;Inflammatory Response;Investigation;Knock-out;Lesion;Link;lipid metabolism;Lipids;Mediating;metaplastic cell transformation;Microglia;misfolded protein;Modeling;Molecular Conformation;mouse model;Mus;nano-string;Nerve Degeneration;Neurodegenerative Disorders;neurodegenerative phenotype;Neuroglia;neuroinflammation;Neurologic;neuron loss;Neurons;neuropathology;neurotoxic;Opsonin;overexpression;particle;Pathogenesis;Pathology;Phagocytes;Phagocytosis;Phenotype;phenotypic biomarker;Play;Prion Diseases;Prions;Property;Protein Isoforms;Proteins;Proteomics;PrP;receptor;response;Risk Factors;RNA;Role;Scrapie;Source;Tauopathies;Therapeutic;Time;Tissues;transcriptome sequencing;transcriptomics;TREM2 gene;Up-Regulation;Work

PROJECT_TITLE: Role of Microglia in Neurodegeneration -Effect of ApoE

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: Columbus

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The fungal pathogen Histoplasma capsulatum causes respiratory and systemic disease by invading and replicating within host cells. Within this host cell, Histoplasma capsulatum scavenges host molecules for its own proliferation during infection, yet these nutritional sources are unknown. This proposal will identify the host molecules consumed by Histoplasma capsulatum when it infects host cells, revealing new therapeutic targets to interfere with the pathogen’s ability to gain metabolic resources from the host.

PI_NAMEs: RAPPLEYE, CHAD A (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Address;alpha ketoglutarate;Amino Acid Permease;Amino Acid Transporter;Amino Acids;Attenuated;Carbon;Catabolism;Cells;Citric Acid Cycle;Coccidioidomycosis;Complement;Consumption;Data;desert fever;Diagnosis;Disease;Environment;Enzymes;Funding Opportunities;fungus;Genes;Genetic;Genetic Screening;genetic testing;Genetic Transcription;Genus Hippocampus;Gluconeogenesis;Glutamate Dehydrogenase;Glutamates;Glycolysis;Goals;Growth;Histoplasma;Histoplasma capsulatum;Histoplasmosis;Immune system;Immunocompetent;Immunocompromised Host;Impairment;In Vitro;in vivo;Individual;Infection;Innate Immune System;interdisciplinary approach;Invaded;Investigation;Isotope Labeling;Lung;Macrophage;Measurement;Metabolic;Metabolic Pathway;metabolic profile;Metabolism;metabolomics;Mitochondria;Molecular;Molecular Biology;Molecular Genetics;mouse model;mutant;Mutation;Mycoses;new therapeutic target;novel strategies;novel therapeutics;Nutrient;Nutritional;Nutritional Requirements;parasitism;pathogen;Pathogenesis;pathogenic fungus;Pathway interactions;Peptides;permissiveness;Phagocytes;Phagosomes;prevent;Proliferating;Reaction;residence;Resources;Respiration;Respiratory Disease;response;RNA Interference;Saccharomyces cerevisiae;Source;Substrate Specificity;Systemic disease;Testing;Therapeutic;Time;transcriptomics;uptake;Virulence;Yeasts

PROJECT_TITLE: Intracellular Proliferation of the fungal pathogen Histoplasma capsulatum

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Aging;Bioengineering;Cardiovascular;Clinical Research;Health Services;Heart Disease;Prevention

ORG_CITY: Chicago

ORG_NAME: NORTHWESTERN UNIVERSITY

ORG_STATE: IL

PHR: Project Narrative  Atrial Fibrillation is a highly prevalent disease in advanced age, a frequent comorbidity to many common diseases, and contributes to increased hospitalization risk and healthcare costs. This project aims to develop a mobile telemonitoring platform to simultaneously monitor symptoms of atrial fibrillation, such as hemodynamic instability and rhythm disturbances, as well as allow the patient and clinician to monitor, predict, and intervene to significant side effects of common pharmacologic treatment of the disease.

PI_NAMEs: TZAVELIS, ANDREAS  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Accelerometer;Adherence;Adult;Affect;Age;aging population;Ambulatory Care;Ambulatory Monitoring;American Heart Association;Amiodarone;Anti-Arrhythmia Agents;Arrhythmia;Atrial Fibrillation;Azithromycin;bioelectricity;Biomechanics;Blood;Blood flow;Blood Pressure;Body Surface;Brain;Cardiac;Cardiac ablation;Cardiac Myocytes;Cardiac Output;Caring;Chest;Chest Pain;Clinical;clinical care;cohort;comorbidity;Complex;Congestive Heart Failure;Contracts;cost;COVID-19 pandemic;Critical Care;Dangerousness;Data;data streams;Dementia;Detection;Diagnosis;Disease;dofetilide;Dose;dronedarone;EFRAC;EKG P Wave;EKG QRS Complex;Elderly;Electric Countershock;Electrocardiogram;Event;flexibility;Funding;Future;Health Care Costs;Healthcare Systems;Heart;Heart Atrium;heart electrical activity;heart function;heart rate monitor;heart rate variability;heart rhythm;hemodynamics;high risk;Holter Electrocardiography;Hospitalization;Hospitals;Hour;human old age (65+);Hydroxychloroquine;incremental cost;Individual;Inpatients;interest;Intervention;Ion Channel;Lead;Left atrial structure;Life;lifetime risk;Light;Lightheadedness;Limb structure;Location;Machine Learning;Measurement;Measures;Medical;Membrane Potentials;Methods;Monitor;monitoring device;Morbidity - disease rate;non-invasive monitor;Operative Surgical Procedures;Organ;Outpatients;Patients;Perfusion;personalized medicine;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Photoplethysmography;Physiologic Monitoring;Physiological;Population;Potassium;Potassium Channel Blockers;prevent;Recommendation;Reporting;Research;research clinical testing;Rest;restoration;Risk;Risk Reduction;sensor;sex;Shortness of Breath;side effect;Signal Transduction;Skin;Sotalol;standard of care;Stream;stroke risk;Stroke Volume;Surface;Symptoms;Syncope;System;Systolic Time Intervals;Tachyarrhythmias;Techniques;Technology;telemonitoring;Therapeutic;Therapeutic Embolization;Thrombotic Stroke;Thrombus;Time;Torsades de Pointes;treatment response;Universities;Ventricular;wearable device;wearable sensor technology;wireless

PROJECT_TITLE: Skin-like, stretchable, and wearable sensors for monitoring QT interval and hemodynamic variables in Atrial Fibrillation


ORG_CITY: BINGHAMTON

ORG_DEPT: BIOLOGY

ORG_NAME: STATE UNIVERSITY OF NY,BINGHAMTON

PHR: PROJECT NARRATIVE Pseudomonas aeruginosa is the cause of many serious human infections, particularly in hospitalized patients with weak immune systems and burn wounds, due to the ability of this human pathogen to form biofilms that are highly resilient to antimicrobial treatment. This proposed research is aimed at elucidating genes and gene functions that enable dispersing bacteria to liberate themselves from the biofilm matrix, regardless of the biofilm matrix composition, and drive the phenotype of dispersed cells. Findings from the proposed study are anticipated to lead to the identification of factors and mechanisms contributing to biofilm dispersion.

PI_NAMEs: PARSEK, MATTHEW R.;SAUER, KARIN  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acute;Adopted;Animal Model;Anti-Bacterial Agents;Antibiotic Resistance;Antibiotics;antimicrobial;Antimicrobial Resistance;Automobile Driving;Bacteremia;Bacteria;Bacterial Adhesins;burn wound;Cells;chronic infection;Classification;Clinic;Clinical;Communities;Complex;Cues;Deoxyribonucleases;Development;Enzymes;Event;Excision;Extracellular Matrix;Future;Gene Expression Profile;gene function;Genes;global health;Glycoside Hydrolases;Goals;Hospitalization;Human;human pathogen;Immune system;In Vitro;in vivo;Individual;Infection;Knowledge;Laboratories;Microbial Biofilms;microorganism;Motility;Mus;Names;Nature;Nosocomial Infections;novel;Operative Surgical Procedures;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Polymers;Predisposition;Process;Proteins;Pseudomonas aeruginosa;Psychological reinforcement;Regulon;Research;resilience;response;Role;Signal Transduction;Societies;spatiotemporal;Swimming;Testing;transcriptome sequencing;Translating;Virulence;World Health Organization;Wound models

PROJECT_TITLE: Dispersion and the Biofilm Matrix of Pseudomonas aeruginosa

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-R(02)M]


ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: Project Narrative Immunotherapies designed to stimulate immune responses against tumors have revolutionized the treatment of cancer. However, successful immunotherapy is dependent on the presentation of tumor antigens on the cell surface, and treatments designed to enhance tumor antigen presentation have great potential to complement immunotherapies. This proposal outlines experiments to evaluate pharmacological modulation of cellular protein folding pathways as a unique strategy to stimulate antigen presentation and drive anti-tumor immune responses.

PI_NAMEs: JAEGER, ALEX  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Address;Advisory Committees;animal imaging;Animal Model;anti-tumor immune response;Antigen Presentation;Antigens;Area;Automobile Driving;Biological Availability;cancer cell;cancer infiltrating T cells;cancer therapy;career;career development;CD8-Positive T-Lymphocytes;Cell surface;Cells;Client;Clinical;Clinical Data;Clinical Trials;Colonic Neoplasms;Colorectal Cancer;Communication;Complement;Data;design;Detection;Development Plans;DNA;DNA Mismatch Repair Protein MSH2;Dose;Ensure;Environment;exome sequencing;experimental study;Exposure to;Faculty;FDA approved;Fluorescence-Activated Cell Sorting;Genetic;Genetically Engineered Mouse;Goals;Heat-Shock Proteins 90;Histology;HSP 90 inhibition;human disease;I-antigen;Immune;immune cell infiltrate;Immune Evasion;immune function;immune modulating agents;Immune response;Immune system;Immunologic Stimulation;immunomodulatory therapies;Immunotherapy;in vivo;inhibitor;insight;Interferon Type II;Isogenic transplantation;Label;Laboratories;LoxP-flanked allele;Lung Adenocarcinoma;Lung Neoplasms;Major Histocompatibility Complex;Malignant Neoplasms;Mediating;Mentorship;Methods;Mismatch Repair Deficiency;Modeling;Molecular Chaperones;Molecular Conformation;mouse model;Mus;mutant;Mutate;Mutation;neoantigens;neoplastic cell;novel therapeutic intervention;Oncogenic;Oral;Pathway interactions;Patients;peptide I;Peptides;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Phase;Positioning Attribute;Preparation;Process;protein folding;Proteins;Proteome;Proteomics;Relapse;research and development;Resistance;response;Running;Signal Pathway;Signal Transduction;skills;small molecule inhibitor;Somatic Mutation;Stress;success;T-Cell Receptor;Testing;Therapeutic Effect;therapy design;tool;Training;Training Activity;treatment strategy;tumor;Tumor Antigens;Tumor Immunity;tumor immunology;Writing

PROJECT_TITLE: Exploring the impact of HSP90 inhibition on antigen presentation and anti-tumor immune responses

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: The research described in this new application has direct relevance to human health in that we are proposing the development of novel therapeutic agents to be used in the treatment of human cancer. We will conduct research exploiting a novel mechanism to impact the DNA damage response to treat human cancer.

PI_NAMEs: GAVANDE, NAVNATH S;TURCHI, JOHN J. (contact)

PROJECT_TERMS: Active Sites;Address;Advanced Development;anti-cancer;anti-cancer therapeutic;Antineoplastic Agents;Automobile Driving;Binding;Biochemical;Biological Availability;Bleomycin;BRCA1 gene;BRCA2 gene;cancer cell;cancer genetics;Cancer Model;cancer therapy;Cells;Characteristics;Chemicals;Chemistry;Chemotherapy and/or radiation;Cisplatin;Clinical;clinically relevant;Combined Modality Therapy;Coupled;Data;design;Development;DNA;DNA Binding;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Sequence Alteration;DNA-dependent protein kinase;DNA-PKcs;Dose;Double Strand Break Repair;Drug Design;Drug Kinetics;drug-like compound;early phase clinical trial;Etoposide;Generations;Genetic;genetic manipulation;Genetic study;Genome Stability;Health;homologous recombination;homologous recombination deficiency;Human;In Vitro;in vivo;inhibitor;innovation;Ionizing radiation;Knowledge;Lung;Maintenance;Malignant neoplasm of lung;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Modeling;Modification;Molecular;Molecular Mechanisms of Action;molecular targeted therapies;nanomolar;Nonhomologous DNA End Joining;novel;novel therapeutics;Outcome;Ovarian;Pathway interactions;Patients;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Pharmacology Study;Phosphotransferases;Play;Property;protein kinase inhibitor;Publishing;Radiation;Radiation induced double strand break;Reagent;recombinational repair;Regulation;repaired;Reporting;Research;response;Roentgen Rays;Role;Series;Signal Pathway;Signal Transduction;small molecule;small molecule inhibitor;Stress;Structure;Structure-Activity Relationship;synthetic lethal interaction;targeted agent;Therapeutic;Therapeutic Agents;Toxic effect;uptake

PROJECT_TITLE: Discovery and development of Ku-targeted small molecule inhibitors: A novel mechanism of DNA-PK inhibition

STUDY_SECTION: DMP

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


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

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Changes in emotions and behavior are early features of frontotemporal dementia that reflect dysfunction in underlying neural systems. Emotion biomarkers that are sensitive to decline in vulnerable brain networks will be critical for monitoring disease progression and treatment response. A better understanding of emotion decline in frontotemporal dementia will help to improve neuroanatomical models of neurological and psychiatric disorders characterized by alterations in emotion.

PI_NAMEs: STURM, VIRGINIA EMILY (contact)

PROGRAM_OFFICER_NAME: STOECKEL, LUKE

PROJECT_TERMS: Affective;Affective Symptoms;Age;Anatomy;Area;Atrophic;Autonomic nervous system;Behavior;behavioral variant frontotemporal dementia;Biological Markers;Biological Models;Brain;C9ORF72;Clinical;clinical subtypes;Clinical Trials;cohort;Data;Deterioration;Disease;Disease Progression;DNA Sequence Alteration;Emotional;Emotions;Empathy;Environment;experience;Facial Expression;Family;Family member;Feeling;follow up assessment;Frontotemporal Dementia;Functional disorder;Genes;Genetic;Goals;GRN gene;Impairment;improved;Individual;innovation;Intervention;Laboratories;Language;longitudinal analysis;Maps;MAPT gene;Measures;Mental disorders;Methods;Modeling;Monitor;Mutation;mutation carrier;Nerve Degeneration;Nervous System Disorder;network dysfunction;neural;Neuroanatomy;neuroimaging;Neurological Models;novel;novel marker;Parasympathetic Nervous System;Participant;Pathology;Patient Self-Report;Pattern;Persons;Phase;Physiology;Populations at Risk;remote assessment;Research;Rest;Sampling;Science;Social Behavior;Structure;Support System;Surveys;Symptoms;Syndrome;System;Techniques;Testing;Time;tool;treatment response;Visit;wearable device

PROJECT_TITLE: Emotion network dysfunction and decline in early frontotemporal dementia

STUDY_SECTION: APDA

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


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

PHR: KPC-2 serine carbapenemase is the major cause of carbapenem resistance in Enterobacteriaceae, deemed an urgent threat by the CDC, while the emergence of NDM-1 metallo-carbapenemase is also raising significant concern. The studies outlined in this proposal aim to develop novel inhibitors against KPC-2 carbapenemase, including dual-activity compounds against NDM-1, and to investigate the unique ability of KPC-2 to hydrolyze nearly all β-lactam antibiotics. The results will provide new chemical scaffolds for novel antibiotic development and provide new understanding of carbapenemase function and inhibition.

PI_NAMEs: CHEN, YU  (contact);RENSLO, ADAM R

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TITLE: Evolution and inhibition of carbapenemase in beta-lactam resistance

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-A(02)M]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Genetics;Neurodegenerative;Neurosciences;Nutrition;Prevention

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: 8. PROJECT NARRATIVE People who carry the APOE E4 gene are at higher risk of Alzheimer’s disease, and they have a different brain metabolic response to interventions involving diet and metabolism, including high fat feeding. In our laboratory, we have consistently shown that E4 carriers cognitively improve after high fat feeding. We want to understand this phenomenon using assessment of cerebral brain flow by MRI and by analysis of the metabolic markers in the spinal fluid.

PI_NAMEs: HANSON, ANGELA JEAN (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: Acute;Alleles;Alzheimer's Disease;Alzheimer's disease risk;Animals;apolipoprotein E-4;Area;arterial spin labeling;Blood flow;Blood Pressure;Body Composition;Brain;brain metabolism;Brain region;Cerebrospinal Fluid;Cerebrovascular Circulation;Cerebrum;Clinical Research;Cognition;Cognitive;cognitive testing;Coupled;Dairy Products;Dairying;Diet;Drops;Dual-Energy X-Ray Absorptiometry;Enrollment;Exhibits;experimental study;Fasting;Fatty acid glycerol esters;feeding;Feeling;Genes;Genotype;Glucose;Glucose Intolerance;glucose tolerance;Glycosylated hemoglobin A;high risk;Hour;Human;Image;improved;Individual;Ingestion;Insulin;Intervention;Investigation;Laboratories;lipidomics;Lipids;Liquid substance;Magnetic Resonance Imaging;Measures;Metabolic;Metabolic Marker;Metabolic Pathway;metabolic profile;Metabolic syndrome;Metabolism;metabolomics;Methods;nutrient metabolism;OGTT;older adult;Oral;Participant;Pathogenesis;Pathogenicity;Pathway interactions;Peripheral;Persons;Play;predictive marker;primary outcome;regional difference;response;Risk;risk variant;Role;Sampling;Satiation;secondary analysis;Spinal Puncture;Systemic blood pressure;Techniques;Technology;Testing;Triglycerides;United States National Institutes of Health;western diet

PROJECT_TITLE: APOE genotype effects on triglycerides and blood flow in the human brain


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Clinical Research;Eczema / Atopic Dermatitis;Immunotherapy

ORG_DEPT: DERMATOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE Atopic dermatitis (AD) is the most common chronic illness of childhood and is often a lifelong disease. AD is among the top 50 most prevalent diseases worldwide, has the second highest disability rank of all nonmalignant skin diseases, and is characterized by chronic and relapsing skin inflammation and itch. Despite our increasing understanding of the role type 2 cytokines and group 2 innate lymphoid cells (ILC2s) in AD, development of new AD therapies is hindered by an incomplete understanding of the immune cell types that regulate the disease beyond these cytokines and immune cells. This proposal will interrogate the relevant identity, spatiotemporal dynamics, and effector mechanisms by which natural killer (NK) cells play a previously unrecognized role in limiting type 2 skin inflammation and AD pathogenesis.

PI_NAMEs: KIM, BRIAN  (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Adoptive Transfer;antiviral immunity;Atopic Dermatitis;Basophils;Biological Response Modifiers;Blood;Cell Death;cell type;Cells;Cessation of life;chemokine;Childhood;Chronic;Chronic Disease;Clinical;cytokine;Development;diagnostic value;disability;Disease;effective therapy;epigenomics;FDA approved;Flow Cytometry;Frequencies;Genetic Transcription;Goals;Human;human RNA sequencing;Immune;Immune Targeting;improved;in vivo;Individual;Inflammation;innovation;insight;Interferon Type II;Interleukin-13;interleukin-13 receptor;Interleukin-4;intravital imaging;Knowledge;Lung;Lymphoid Cell;mast cell;Molecular;Mus;Natural Killer Cells;Non-Malignant;novel;novel therapeutics;Parabiosis;Pathogenesis;Pathway interactions;Patients;Phase III Clinical Trials;Phenotype;Play;Population;Predisposition;primary endpoint;Production;Proteins;Pruritus;Publishing;Regulation;Relapse;Reporter;Research;Resolution;response;Role;Severity of illness;single cell ATAC-seq;single-cell RNA sequencing;Skin;skin disorder;spatiotemporal;targeted treatment;Testing;Th2 Cells;Therapeutic;therapeutic target;Tissues;translational medicine;Translational Research;Tumor Immunity

PROJECT_TITLE: Natural Killer Cell Regulation of Skin Inflammation

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


NIH_SPENDING_CATS: Cancer;Clinical Research;Immunotherapy;Lung;Lung Cancer;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: The discovery that there are simple ways to turn our own defense mechanisms against cancer was revolutionary, leading to unprecedented cures of some patients with advanced disease that had never been possible with surgery, radiation, and chemotherapy. Unfortunately, this miraculous treatment, called immunotherapy, does not work as often as it should, and it remains a mystery why people with the same type of cancer will have different responses to the same treatment. The experiments being supported by this project are intended to create a blood test to predict whether cancer immunotherapy will work or not and also to provide a solution for patients who are not likely to respond, by adding a second medication to their treatment, which will increase their chances of responding to immunotherapy.

PI_NAMEs: REINER, STEVEN L (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Address;advanced disease;anti-cancer;anti-PD-1;anti-PD1 therapy;Antigens;Biological Markers;Blood;Blood specimen;Blood Tests;blood treatment;cancer care;cancer immunotherapy;Cancer Patient;cancer type;candidate marker;CD8-Positive T-Lymphocytes;Cell Differentiation process;Cell division;cell regeneration;Cells;Cellular biology;chemotherapy;Clinical;clinical practice;Clinical Trials;Clone Cells;confocal imaging;Confocal Microscopy;Consensus;daughter cell;Defense Mechanisms;disorder control;Dose;Equilibrium;experimental study;Flow Cytometry;Frequencies;Functional disorder;Head and Neck Squamous Cell Carcinoma;Image Cytometry;immune checkpoint blockade;Immunity;Immunofluorescence Immunologic;Immunotherapy;improved;in vivo;insight;kindred;Lesion;Link;Malignant Neoplasms;Malignant Squamous Cell Neoplasm;Minority;Mitotic;Morphology;Mus;Nature;Non-Small-Cell Lung Carcinoma;novel strategies;Operative Surgical Procedures;Output;patient response;Patients;PD-1 blockade;peripheral blood;Peripheral Blood Mononuclear Cell;Persons;Pharmaceutical Preparations;Physiologic pulse;PIK3CG gene;pre-clinical;predictive marker;Production;progenitor;Proliferating;Radiation therapy;receptor;regenerative;Resistance;response;response biomarker;self-renewal;Siblings;Signal Transduction;Sister;stem cell differentiation;stem cell division;stemness;T cell differentiation;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;Testing;Tissues;translational applications;transmission process;tumor;tumor growth;Tumor Immunity;Tumor Tissue;Work

PROJECT_TITLE: Strategies to predict and overcome resistance to cancer immunotherapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TIR-W(01)Q]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Genetics;Infectious Diseases;Urologic Diseases

PHR: PROJECT NARRATIVE Globally, up to 40% of hospital-acquired infections are catheter-associated urinary tract infections (CAUTIs). Proteus mirabilis is a key causative agent of CAUTI due to its ability to generate bladder stones and build crystalline biofilms that block catheters. This study aims to identify and define key regulatory networks in P. mirabilis that drive infection in the urinary tract.

PI_NAMEs: FITZGERALD, MADISON JANE (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Accounting;Adherence;Agar;Antibiotic Resistance;Bacteria;Biochemical;Bioinformatics;bioinformatics tool;Biological Assay;Biology;Bladder;Bladder Calculi;catheter associated UTI;Catheters;Cell Physiology;comparative;cost;Cues;Data Set;Development;Environment;Essential Genes;experimental study;fitness;Flagella;follow-up;Future;Genes;genetic approach;Genetic Transcription;Genome;genome-wide;Goals;Growth;Harvest;healthcare burden;Healthcare Systems;Hour;In Vitro;in vivo;Individual;inducible gene expression;Infection;interest;Iron;Knowledge;knowledge base;Learning;Libraries;Literature;Maintenance;Mediating;member;Methodology;Methods;Microbial Biofilms;Molecular;mouse model;Mus;Mutagenesis;mutant;Names;Natural Resistance;Nosocomial Infections;novel;novel therapeutics;Nutrient;Organism;Outcome;Output;pathogen;Pathogenesis;Patients;Phenotype;Physicians;Plasmids;Polymyxins;Production;promoter;Proteus mirabilis;Publishing;Quantitative Reverse Transcriptase PCR;Regulon;response;screening;Source;System;targeted treatment;Techniques;Testing;Tetracycline Resistance;Therapeutic;Toxin;transcription factor;transcriptome sequencing;transcriptomics;transposon sequencing;United States;uptake;Urease;Urinary Calculi;Urinary tract;Urinary tract infection;Urination;Urine;Vaccines;vector;Virulence;Virulence Factors;Visit

PROJECT_TITLE: Systematic analysis of Proteus mirabilis transcriptional regulators that drive uropathogenesis


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

ORG_CITY: ALBANY

ORG_NAME: ALBANY MEDICAL COLLEGE

PHR: Obstructive sleep apnea (OSA) is a major public health problem, which is more prevalent in older individuals. The sleep-related decrease of the tonus of upper airway muscles, which keeps airway open in wakefulness, is a key neurological cause of the airway occlusion in most OSA patients. Since noradrenergic neurons significantly contribute to the maintenance of upper airway muscle tone, we will determine whether the functioning of these noradrenergic neurons is impaired with age; this information will be helpful for developing proper therapeutic strategies for the clinical management of OSA in older patients.

PI_NAMEs: FENIK, VICTOR BORISOVICH;RUKHADZE, IRMA  (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Acceleration;Adult;Age;age effect;age related;age related changes;age-related disease;Aging;aging population;airway muscle;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid deposition;Anatomy;Arousal;Axon;base;Brain Stem;Cardiovascular system;Cell Nucleus;cell type;Chronic;Clinical;Clinical Management;Clinical Research;Clinical Trials;Coupling;Data;density;design;Dilator;Effectiveness;Elderly;Event;experience;experimental study;Female;Functional disorder;genetic approach;genioglossus muscle;Health;Hypercapnia;hypoglossal nucleus;Hypoxia;Impairment;improved;Link;locus ceruleus structure;Maintenance;male;Maps;Mental Depression;Metabolic;Methods;middle age;Molecular Genetics;Morbidity - disease rate;mortality;Motor Neurons;mouse model;Mus;Muscarinics;Muscle;Muscle Tonus;nerve injury;nerve supply;neurochemistry;Neurocognitive;Neurologic;Neurons;non rapid eye movement;noradrenergic;normal aging;novel;Obstructive Sleep Apnea;old mice;older adult;older patient;Older Population;Pathogenesis;Pathology;Patients;Pattern;pharmacologic;Play;pressure;Prevalence;Preventive;Prosencephalon;Public Health;Quality of life;Recurrence;Reflex action;REM Sleep;Reporting;Risk Factors;Role;Severities;Sleep;Sleep Apnea Syndromes;Sleep Deprivation;Sleep Fragmentations;System;Testing;Therapeutic;Tongue;Translational Research;transmission process;Viral Vector;Wakefulness;Work

PROJECT_TITLE: The impact of aging on the functional and anatomical coupling between brainstem noradrenergic neurons and upper airway muscles

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


NIH_SPENDING_CATS: Autoimmune Disease;Diabetes

ORG_CITY: SALT LAKE CITY

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE The current project investigates the role of diabetogenic CD8 T cells in autoimmune type I diabetes (T1D) from the perspective of beta-cell self-antigen recognition. This will be undertaken by novel biophysical single cell/single molecule methods in combination with cutting edge biological/immunological assays to elucidate the underlying molecular mechanisms. This will provide mechanistic understanding of beta-sell self-recognition (compared to normal foreign-recognition) and offer new insights for future direct therapeutical targeting of diabetogenic CD8 T cells.

PI_NAMEs: LIU, BAOYU  (contact)

PROGRAM_OFFICER_NAME: SPAIN, LISA M

PROJECT_TERMS: Affinity;Antigen-Presenting Cells;antigen-specific T cells;Antigens;Autoantigens;Autoimmune;Autoimmune Diabetes;Autoimmunity;autoreactive T cell;autoreactivity;Avidity;Beta Cell;Binding;Biological;Biological Markers;Biophysics;CD8 receptor;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Communication;Cells;central tolerance;Clone Cells;Data;Development;Diabetes Mellitus;diabetes pathogenesis;diabetogenic;Disease;effector T cell;Endowment;Environment;Event;Future;G6PC2 gene;glycosylation;Immune response;Immune system;Immunology procedure;Inbred NOD Mice;insight;Insulin;Insulin-Dependent Diabetes Mellitus;Investigation;Islets of Langerhans;Kinetics;Life;Measures;Mediating;Methods;MHC Interaction;Molecular;mouse model;novel;novel therapeutic intervention;Outcome;Pancreas;Pathogenicity;Patient Care;Pattern;Peptide Fragments;Peptide/MHC Complex;Peripheral;peripheral tolerance;Phenotype;Polysaccharides;receptor;receptor binding;Reporting;Role;Self Tolerance;single molecule;Surface;T cell response;T-Cell Receptor;T-Lymphocyte;TCR Activation;Testing;therapeutic target;Thymocyte Selection;Thymus Gland;Time;Tissues;transcriptomics;Travel;two-dimensional

PROJECT_TITLE: Beta-cell self-antigen recognition by diabetogenic CD8 T cells


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Prevention;Substance Misuse

ORG_CITY: BELTSVILLE

ORG_NAME: PACIFIC INSTITUTE FOR RES AND EVALUATION

PHR: PROJECT NARRATIVE This study will determine whether the California responsible beverage service (RBS) training law has an impact on alcohol-related motor vehicle crashes, and whether “usual and customary” training will match the efficacy of an online WaytoServe RBS training program in reducing over-service of alcohol to apparently-intoxicated pseudopatrons at licensed on-premises establishments such as bars and restaurants. This study will also conduct a state-wide survey of owners and managers of alcohol outlets to identify barriers and facilitators to their compliance with the new law and its intended effects for improving server behavior. Findings of this study will have implications for state and local regulatory policies regarding RBS training, and for future research on the effectiveness of RBS training.

PI_NAMEs: SALTZ, ROBERT F. (contact)

PROGRAM_OFFICER_NAME: FREEMAN, ROBERT

PROJECT_TITLE: Assessing the impact of The California Alcohol Server Training Act

STUDY_SECTION: CIHB

STUDY_SECTION_NAME: Community Influences on Health Behavior Study Section[CIHB]


ORG_CITY: AUGUSTA

ORG_DEPT: PHYSIOLOGY

ORG_NAME: AUGUSTA UNIVERSITY

PHR: Narrative Atherosclerosis is a chronic inflammatory disease of the artery walls that leads to heart attacks and strokes. We discovered in mouse models that vaccination with short sequences of APOB, a protein associated with cholesterol transport, can reduce the inflammation in the artery wall. The proposed work will lay the mechanistic groundwork for developing an atherosclerosis vaccine that is expected to benefit tens of millions of people in the US and billions of people worldwide.

PI_NAMEs: LEY, KLAUS F. (contact)

PROGRAM_OFFICER_NAME: HASAN, AHMED A  K

PROJECT_TERMS: Adoptive Transfer;Antibodies;Aorta;Apolipoprotein E;Apolipoproteins B;Arteries;Atherosclerosis;B-Lymphocytes;Bar Codes;Blood Vessels;Cardiovascular Diseases;CD4 Positive T Lymphocytes;cell type;Cells;Cholesterol;chronic inflammatory disease;Clinical;Clinical Data;Collecting Cell;Color;Cytometry;Data Set;Diet;Disease;DNA Methylation;Dose;effector T cell;Epigenetic Process;Epitopes;Exogenous Factors;FOXP3 gene;Gender;High Fat Diet;histone methylation;HIV;Human;human data;humoral immunity deficiency;Immunotherapy;improved;in vivo;Incubated;Inflammation;Inflammatory;insight;Interleukin-2;Macrophage;Measures;Minor;mouse model;Mus;Myocardial Infarction;peptide B;Peptides;Peripheral Blood Mononuclear Cell;Persons;phenotypic data;Population;prevent;Proteins;Reagent;Regulatory T-Lymphocyte;Research Design;Role;single-cell RNA sequencing;Solid;Stroke;T cell receptor repertoire sequencing;T-Lymphocyte;Testing;transcription factor;transcriptome;Translating;Vaccination;vaccination protocol;vaccine efficacy;vaccine evaluation;vaccine formulation;Vaccines;Woman;Work

PROJECT_TITLE: Vascular macrophages and T cells in atherosclerosis


NIH_SPENDING_CATS: Asthma;Chronic Obstructive Pulmonary Disease;Infectious Diseases;Lung;Neurosciences

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Narrative  Basic and clinical research over the past decade is shedding new light on the major role played by the nervous system in asthma, COPD, and chronic coughing. This proposal focuses on unraveling the chemical and ionic mechanisms of airway nerve activation and on identifying the specific aspects of airway inflammation, especially during early life that leads to a hyperactive neuronal state in the airways. The findings will increase our understanding of airway biology, and will continue to define new therapeutic targets aimed at reducing the suffering of those with inflammatory airway diseases.

PI_NAMEs: UNDEM, BRADLEY JOEL (contact)

PROGRAM_OFFICER_NAME: LU, JINING

PROJECT_TERMS: Adult;afferent nerve;Airway Disease;airway hyperresponsiveness;airway inflammation;Animals;Asthma;Autacoids;Award;Basic Science;Biology;C Fiber;Chemicals;Chronic;Chronic Obstructive Pulmonary Disease;Clinical Research;Coughing;critical period;cytokine;Disease;Functional disorder;Funding;Grant;Human;Hyperactivity;Image;Infection;Inflammation Mediators;Inflammatory;interest;Laboratories;Life;Mentors;Methodology;Methods;Modernization;Nature;Nerve;nerve supply;Nervous System;Neurobiology;Neuronal Plasticity;Neurons;neurophysiology;Neurosciences;Neurosciences Research;new therapeutic target;Play;Research Personnel;respiratory;Respiratory System;Role;Secondary to;Sodium Channel;System;Techniques;Technology;user-friendly;Virus Diseases;Visceral;voltage

PROJECT_TITLE: Neurobiology of the Bronchopulmonary System


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

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

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative. Our preliminary results show that cocaine dose-dependently downregulates a novel, cell type-specific molecular substrate in the midbrain, KCC2, that could be targeted to treat cocaine use disorder. Cocaine taking downregulates KCC2, which disrupts midbrain GABAergic circuitry and augments subsequent cocaine-taking behavior. Using a rodent model of voluntary cocaine taking and seeking we will quantify this cocaine-induced circuitry neuroadaptation, and we will apply two mechanistically different pharmacotherapies to enhance KCC2 function to attenuate or prevent cocaine self-administration and reinstatement, which is an animal model of relapse.

PI_NAMEs: DANI, JOHN A. (contact)

PROGRAM_OFFICER_NAME: NAIR, SUNILA GOPI

PROJECT_TERMS: Abstinence;addiction;Animal Model;Attenuated;Behavior;cell type;Centers for Disease Control and Prevention (U.S.);Central Nervous System;Cessation of life;chloride-cotransporter potassium;Chlorides;Cocaine;Cocaine Abuse;cocaine exposure;cocaine relapse;cocaine relapse prevention;cocaine seeking;cocaine self-administration;cocaine use;Cocaine use disorder;Consumption;Data;Dependence;dopaminergic neuron;Dose;Down-Regulation;drug action;Drug Administration Routes;experimental study;Extinction;FDA approved;gamma-Aminobutyric Acid;Goals;Hospitalization;Human;Infusion procedures;Maintenance;Measures;Membrane;Midbrain structure;Modeling;Molecular;Molecular Target;neuroadaptation;Neurons;new therapeutic target;novel;Pathway interactions;Pharmaceutical Preparations;Pharmacological Treatment;Pharmacotherapy;Phase;Phosphorylation;Physiological;prevent;promoter;Proteins;Protocols documentation;Public Health;Relapse;Research;Rodent Model;Self Administration;side effect;stimulant abuse;symporter;Testing;Therapeutic;therapeutic target;Time;United States National Center for Health Statistics

PROJECT_TITLE: Altered Midbrain GABAergic Circuitry Drives Greater Cocaine Self-administration

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS]


NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Data Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Radiation Oncology

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: PROJECT NARRATIVE Patients with cancer undergoing cancer treatments such as radiation therapy or chemotherapy may require emergency department (ED) visits or hospitalization, a public health need that affects treatment outcomes, quality of life, and costs to patients and the healthcare system. We have developed artificial intelligence (AI) models using routine electronic health record data and mobile device step count data that have been demonstrated to predict and reduce ED visits and hospitalizations. The goal of this work is to assess and improve how well these approaches work across a network of diverse hospitals and make the benefits of this AI-supported care apply more broadly and ensure access and equal healthcare to all patients.

PI_NAMEs: HONG, JULIAN CLINT (contact)

PROGRAM_OFFICER_NAME: WOLFF-HUGHES, DANA L

PROJECT_TERMS: Accident and Emergency department;acute care;Address;Affect;Apple;Artificial Intelligence;artificial intelligence model;Asian;Black race;Boston;California;cancer care;cancer therapy;Caring;chemoradiation;chemotherapy;Chemotherapy and/or radiation;Clinical;Clinical Data;clinical practice;Clinical Trials;cohort;Community Practice;comorbidity;Complement;Computer software;cost;COVID-19 pandemic;Data;data harmonization;Data Sources;Devices;Disease;Early identification;Ecosystem;Electronic Health Record;Emergency department visit;Ensure;Equity;Evaluation;fitbit;Future;Geography;Goals;handheld mobile device;Health;health care delivery;health care settings;health data;health equality;Healthcare;Healthcare Systems;high risk;Hospital Departments;Hospitalization;Hospitals;improved;Informatics;Institution;Intervention;Israel;Machine Learning;machine learning algorithm;machine learning model;machine learning prediction;machine learning prediction algorithm;Malignant Neoplasms;Medical center;Medicare;Modeling;Monitor;multimodal learning;Native Americans;Non-Small-Cell Lung Carcinoma;Oncology;Outcome;Outpatients;Patient Care;patient population;Patients;Performance;personalized predictions;portability;practice setting;predictive modeling;Procedures;prospective;Public Health;Quality of life;Race;Radiation therapy;Randomized;randomized, controlled study;Randomized, Controlled Trials;remote health care;Research;Resources;rural Americans;San Francisco;socioeconomics;success;Supportive care;symptom management;symptom treatment;symptomatic improvement;System;Systemic Therapy;tool;Treatment outcome;Underserved Population;United States;United States Centers for Medicare and Medicaid Services;Universities;Validation;Washington;wearable device;Work

PROJECT_TITLE: Multi-institutional validation of a multi-modal machine learning algorithm to predict and reduce acute care during cancer therapy

STUDY_SECTION: CIDH

STUDY_SECTION_NAME: Clinical Informatics and Digital Health Study Section[CIDH]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Genetics;Infectious Diseases;Malaria;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BOSTON

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

ORG_STATE: MA

PHR: PROJECT NARRATIVE Malaria, one of the world’s most devastating diseases, afflicts 200-400 million people and kills nearly 500,000 annually, and these numbers will increase as resistance to currently used drugs spreads. This project aims to determine the physiological pathways which enable rapid drug-tolerance and establish the basis for the adaptive proline response in the parasite. We apply an integrated chemogenomic approach combining Plasmodium genetics, metabolomic flux balance analysis, quantitative mass spectrometry based-proteomics, and rational pharmacology to identify and validate mechanistically relevant targets that can be exploited for the prevention and reversal of drug resistance.

PI_NAMEs: MAZITSCHEK, RALPH  (contact);WIRTH, DYANN F

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Address;amino acid metabolism;Amino Acyl-tRNA Synthetases;analog;Anti-malarials;applied biomedical research;Artemisinins;Binding;Biochemical;Biology;Cell Line;Cell Physiology;Cellular Stress;Cessation of life;chemotherapy;Chinese Traditional Medicine;Combined Modality Therapy;Cytoplasm;Data;Dependence;Development;Disease;DNA sequencing;Drug resistance;Drug Targeting;Drug Tolerance;Drug usage;Equilibrium;Evolution;Exhibits;Expression Profiling;febrifugine;Fever;Genes;Genetic;genome-wide;Genomic approach;Genomics;Goals;Halofuginone;Herbal remedies;Homeostasis;in vivo;inhibitor;insight;Life;Liver;Malaria;Maps;Mass Spectrum Analysis;Mediating;Mediator;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Molecular;Molecular Target;Natural Products;new therapeutic target;next generation;non-genetic;novel;novel therapeutics;Organism;Parasite resistance;Parasites;Parasitic Diseases;Parasitology;Pathway interactions;Persons;Pharmaceutical Preparations;Pharmacology;Physiological;Plasmodium;Plasmodium falciparum;Point Mutation;prevent;Prevention;Process;Proline;proline-tRNA;Protein Isoforms;Proteome;Proteomics;Publishing;Regulation;Reporting;Research;Research Project Grants;Resistance;resistance mechanism;response;Signal Transduction;Source;synergism;Synthesis Chemistry;targeted treatment;Technology;Transfer RNA;Treatment Efficacy;Treatment Failure;Up-Regulation;Work

PROJECT_TITLE: Proline homeostasis: a novel mediator of drug tolerance in Plasmodium falciparum

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-S(02)M]