ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Rural Health;Social Determinants of Health

ORG_CITY: NEW HAVEN

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE  Rural individuals face a disproportionate burden of negative mental health outcomes. Emerging technology in psychiatry uses machine learning and human neuroimaging data to inform clinical decisions such as treatment choices. This study investigates how this machine learning technology itself may drive mental health disparities by performing more poorly in rural populations and means of reducing disparities by creating models that perform equitably within underrepresented populations.

PI_NAMEs: ADKINSON, BRENDAN  (contact)

PROGRAM_OFFICER_NAME: LAI, GABRIEL Y

PROJECT_TERMS: Adolescent;Affect;Age;Algorithms;Area;Attention;Behavior;Brain;brain based;brain behavior;career;Clinical;clinical decision-making;Cognition;Cognitive;Cognitive deficits;cognitive development;cognitive task;Complex;connectome;connectome based predictive modeling;Data;Data Collection;Data Set;Development;developmental disease;Diagnosis;disparity reduction;Emerging Technologies;Ensure;Equity;Exclusion;Face;Functional Magnetic Resonance Imaging;Geographic Locations;Geography;health disparity;Healthcare;Human;Individual;Learning;Machine Learning;machine learning model;Measures;Mental disorders;Mental Health;metropolitan;model design;Modeling;Modernization;Moods;Nature;neuroimaging;novel;Outcome;Participant;Pattern;Performance;Physicians;Population;predictive modeling;prevent;psychiatric symptom;Psychiatry;Research;Rest;Rural;rural area;rural health disparities;rural patients;Rural Population;rural residence;Sampling;Sampling Studies;Scientist;Site;Symptoms;Techniques;Technology;Testing;tool;Training;Translations;treatment choice;Treatment outcome;Underrepresented Populations;United States;urban area;urban residence;Validation;verbal;virtual

PROJECT_TITLE: Characterizing neuroimaging 'brain-behavior' model performance bias in rural populations


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: BOSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

ORG_STATE: MA

PHR: Given the strong relationship between social adversity (e.g., homelessness, food insecurity) and health, policy makers suggest routine screening and referral (S&R) for unmet social and economic needs in the clinical setting. This call has catalyzed a small but promising evidence base indicating that unmet need S&R can lead to patients’ connection to resources, unmet need reduction, and potential improvements in health. However, this evidence base focuses on unmet needs in urban settings. This means we lack the knowledge needed to adapt unmet need S&R to the unique needs of rural VA facilities and the rural Veterans they serve. We propose to examine unmet needs among rural Veterans, how they manifest, and the infrastructure available to identify and address these needs. With this knowledge and in collaboration with the individuals in the setting where the intervention will ultimately be implemented, the study will develop the specifications for the adapted unmet need S&R intervention for rural Veterans. Future study will implement and evaluate the intervention.

PI_NAMEs: GUREWICH, DEBORAH  (contact)

PROJECT_TERMS: Accounting;Address;Cardiovascular Diseases;care outcomes;Caring;Characteristics;Clinical;Collaborations;Communities;comorbidity;COVID-19;Data;Development;Disease;Economic Conditions;economic need;Economics;Effectiveness;effectiveness/implementation study;Epidemiology;Evaluation;evidence base;experience;Feedback;food insecurity;Future;Goals;Health;health equity;Health Services Research;Healthcare;Homelessness;Human Resources;implementation barriers;improved;Individual;Inequity;information gathering;Infrastructure;innovation;Intervention;intervention refinement;Interview;Knowledge;Logistics;Medical center;Methodology;Methods;Mission;Modeling;New England;novel;Outcome;Outcome Assessment;Patients;Phase;pilot test;Policy Maker;Population;Positioning Attribute;preference;Prevalence;Process;Provider;Randomized, Controlled Trials;Replicating Effective Programs;Research;research and development;Resources;Risk;routine screening;Rural;rural America;Rural Community;Rural Health;rural setting;Scientific Advances and Accomplishments;screening;Service setting;Services;Site;social;social adversity;Social Conditions;social health determinants;Social Network;Social Work;Specific qualifier value;Suicide;Surveys;System;Time;United States Department of Veterans Affairs;urban area;urban setting;user centered design;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Addressing Social Determinants of Health Among Rural Veterans

STUDY_SECTION_NAME: Social Determinants of Health[HS2A]


ADMINISTERING_IC: NR

ED_INST_TYPE: SCHOOLS OF NURSING

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Atherosclerosis;Behavioral and Social Science;Cardiovascular;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Neurosciences;Patient Safety;Racial and Ethnic Minority Health Research;Sleep Research;Social Determinants of Health

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Black Americans have higher death rates and worse outcomes than White Americans following open heart surgery. These racial disparities are not well understood; however, disruptions in sleep, circadian rhythms, and blood sugar in the intensive care unit may explain a significant portion of this disparity. Therefore, the purpose of this study is to understand the role of novel connections between an individual’s sleep, circadian rhythm, and blood sugar pattern in the intensive care unit environment following open heart surgery.

PI_NAMEs: BOLTON, PAMELA  (contact)

PROGRAM_OFFICER_NAME: HUSS, KAREN

PROJECT_TERMS: actigraphy;Adult;Affect;Antibiotics;Area;Behavior Therapy;Behavioral;Black American;Black race;Blood Glucose;Cardiac Surgery procedures;Cardiovascular Diseases;Cardiovascular system;Caring;caucasian American;Cessation of life;Characteristics;circadian;Circadian Dysregulation;Circadian Rhythms;Cities;Clinical;Communities;Complex;Convalescence;Coronary artery;Coronary Artery Bypass;Critical Illness;Death Rate;deprivation;Diabetes Mellitus;Disparity;Environment;Foundations;Future;Guidelines;health disparity;high risk;Hospitals;Hyperglycemia;Hypoglycemia;immune function;Impairment;improved;Individual;Infusion procedures;Inpatients;Insulin;Insulin Resistance;insulin sensitivity;Intensive Care Units;Intervention Studies;Length of Stay;lens;Link;Longitudinal Studies;Measures;Morbidity - disease rate;mortality;mortality disparity;National Institute of Nursing Research;Not Hispanic or Latino;novel;Ohio;Operative Surgical Procedures;Outcome;outcome disparities;Patients;Pattern;Persons;Physiology;Population;Population Heterogeneity;Postoperative Period;Process;racial disparity;racial diversity;racial minority;racial population;repaired;Research;Research Activity;response;Risk;Role;Sleep;Sleep disturbances;social health determinants;socioeconomics;Strategic Planning;Stress;Training;Universities;University Hospitals;urban area

PROJECT_TITLE: Racial Disparities in Sleep, Circadian Rhythm, and Glucoregulation Among Individuals Post-Coronary Artery Bypass Surgery

STUDY_SECTION: NRRC

STUDY_SECTION_NAME: Nursing Science Review Committee[NRRC(86)]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Skin Cancer

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Core 2. Biostatistics and Bioinformatics Narrative The Biostatistics and Bioinformatics Core provides specialized analysis services to the clinical, laboratory,  translational and -omics research projects of the MSCP SPORE to ensure that experiments are efficiently  designed, and data are analyzed in a rigorous and reproducible fashion by analysts familiar with cancer in  general and melanoma and other skin cancers in specific.

PI_NAMEs: WANG, HONG  (contact)

PROJECT_TERMS: Address;Advocacy;Advocate;anti-cancer research;Awareness;Bioinformatics;Biometry;Budgets;Cancer Center;career;Clinic;Clinical;clinical translation;Clinical Trials;Collaborations;Communication;Communities;compare effectiveness;Contracts;Data;Data Analyses;data sharing;Dedications;Dermatology;design;Development;Endowment;Ensure;Evaluation;experience;Experimental Designs;experimental study;Extramural Activities;Faculty;Fostering;Funding;Genomics;Goals;Guidelines;Human Resources;improved;In Vitro;in vivo;Industry;Institution;International;Laboratories;Lead;Machine Learning;Malignant Neoplasms;Medical center;meetings;Melanoma;Melanoma patient;Methods;Mission;Monitor;operation;outreach;Patient-Focused Outcomes;Periodicals;Pharmacologic Substance;Pilot Projects;programs;Reproducibility;Research;Research Personnel;Research Project Grants;Resource Allocation;Resource Sharing;Resources;Schools;Services;Skin;Skin Cancer;success;Techniques;translational goal;translational progress;Translational Research;translational scientist;Universities;Vision;Work

PROJECT_TITLE: Core 2: Biostatistics and Bioinformatics Core


ED_INST_TYPE: SCHOOLS OF MEDICINE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Genetic Testing;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Human Genome;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Telehealth

ORG_CITY: RICHMOND

ORG_DEPT: PEDIATRICS

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE The overarching goal of this proposed multi-center research is to compare and contrast the nature of cancer genetic counseling encounters and patient-centered outcomes between Black and White patients in the naturalistic clinical setting. We will conduct an observational study with a convergent mixed methods research design, analyzing video-recorded cancer genetic counseling encounters both qualitatively and quantitatively and linking those data to pre-encounter survey data (to identify provider factors associated with the nature of cancer genetic counseling encounters), post-encounter survey data (to assess the role of cancer genetic counseling encounters in predicting self-reported patient-centered outcomes), and data from medical chart reviews (to assess the role of cancer genetic counseling encounters in predicting genetic test uptake). Findings from this proposed study enables researchers to identify specific aspects of cancer genetic counseling encounters (i.e., patient-counselor communication and clinical recommendations) that are modifiable and are directly associated with patient-centered outcomes.

PI_NAMEs: HAGIWARA, NAO ;QUILLIN, JOHN M. (contact)

PROGRAM_OFFICER_NAME: FERRER, REBECCA

PROJECT_TERMS: Address;African American;Belief;black patient;Black Populations;Black race;Cancer Control;cancer genetics;cancer health disparity;cancer risk;Clinical;clinical encounter;Code;Communication;Communication Research;Consent;cost effective;COVID-19;current pandemic;Data;Development;Disparity;Educational process of instructing;empowerment;Feeling;frontier;Genetic Counseling;genetic counselor;genetic predictors;genetic testing;Genetic testing for cancer risk;Genetic Transcription;Goals;health care disparity;Health Disparities Research;Healthcare;Knowledge;Linguistics;Link;Malignant Neoplasms;Medical;Modality;Multicenter Studies;National Cancer Institute;Nature;Observational Study;Outcome;pandemic disease;Patient Self-Report;patient-clinician communication;Patient-Focused Outcomes;Patients;Pattern;Persons;Physicians;Play;Prejudice;Prevention;Process;Professional counselor;programs;Provider;provider factors;Race;racial bias;racial disparity;racial minority;racial population;racial prejudice;Recommendation;Research;Research Design;Research Methodology;Research Personnel;Risk Assessment;Role;satisfaction;Scientific Advances and Accomplishments;Stereotyping;Surveys;telehealth;Testing;testing uptake;theories;Therapeutic;Training;Training Programs;Trust;Video Recording;Work

PROJECT_TITLE: Racial disparities in cancer genetic counseling encounters in the naturalistic clinical setting

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


NIH_SPENDING_CATS: Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Obesity;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health;Uterine Cancer;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: The incidence and mortality of uterine cancer are rising dramatically in the U.S., especially among black. We will develop three natural history models of uterine to estimate the harms, benefits and cost-effectiveness of screening, prevention and treatment options for uterine cancer. We will likewise use these models to address areas of public health relevance including racial disparities, the growing obesity epidemic in the U.S., and changing rates of hysterectomy for benign gynecologic disease, all of which will have profound effects on the incidence and mortality of uterine cancer in the coming decades.

PI_NAMEs: BICKELL, NINA A.;BLANK, STEPHANIE V.;ELKIN, ELENA B;HAVRILESKY, LAURA J;KONG, CHUNG YIN ;WRIGHT, JASON  (contact)

PROGRAM_OFFICER_NAME: TATALOVICH, ZARIA

PROJECT_TERMS: Address;Adjuvant;Adjuvant Therapy;Affect;Age;Area;Benign;black women;Cancer Control;Cancer Etiology;Cancer Intervention and Surveillance Modeling Network;cancer prevention;Cessation of life;Characteristics;Chemoprevention;Clinical;clinical care;Cohort Effect;Communities;comorbidity;comparative;Consensus;cost;cost effectiveness;Costs and Benefits;Data;Death Rate;Decision Making;Disease;Disparity;Early Diagnosis;Effectiveness;Environmental Risk Factor;Epidemiologic Factors;Epidemiology;Female Genital Diseases;Funding;Future;Genetic Predisposition to Disease;Goals;Hereditary Nonpolyposis Colorectal Neoplasms;High Risk Woman;Hysterectomy;Immunotherapy;improved;Incidence;Incubators;Individual;Localized Malignant Neoplasm;Malignant Neoplasms;men;Modeling;mortality;mortality disparity;Natural History;Neoplasms;new technology;new therapeutic target;Newly Diagnosed;novel;novel therapeutic intervention;Obesity;Obesity Epidemic;obesity prevention;Operative Surgical Procedures;Pathway interactions;Patients;Patterns of Care;Policy Maker;Population;Prevalence;Prevention;prevention effectiveness;Prevention strategy;Prognosis;Prophylactic treatment;Provider;public health relevance;racial disparity;rate of change;Recommendation;Recurrent disease;Regimen;Resources;Risk;Risk Factors;Role;routine screening;screening;social health determinants;social influence;Testing;Time;tool;treatment comparison;Treatment Cost;treatment strategy;trend;tumor;Uterine Cancer;Uterus;web-based tool;White Women;Woman;Work

PROJECT_TITLE: Comparative Modeling for the Prevention and Control of Uterine Cancer


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: DALLAS

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE Sensory hypersensitivity is a common problem for individuals with Fragile X Syndrome, a leading cause of autism and inherited intellectual disability, but the mechanism that mediates this process is not fully understood. The proposed research will investigate of a previously unstudied neurotransmitter receptor to cortical network dysfunction. Results are expected to provide crucial knowledge of the etiology of dysregulated cortical development in Fragile X Syndrome and potential new therapeutic targets using translationally relevant biomarkers of brain function.

PI_NAMEs: SHEDD, ALEYA MICHELLE (contact)

PROGRAM_OFFICER_NAME: KAU, ALICE S

PROJECT_TERMS: Acute;Affect;Astrocytes;audiogenic seizure;Auditory;autism spectrum disorder;awake;Biological Markers;Brain;cell cortex;cell type;Cells;Collaborations;common symptom;Complement;confocal imaging;Cortical Synchronization;Data;design;Development;Electroencephalography;Etiology;excitatory neuron;experimental study;Fragile X Syndrome;frontal lobe;Functional disorder;Genetic Markers;Genetic Transcription;Goals;Human;Hypersensitivity;Impaired cognition;in vivo;Individual;Inherited;inhibitory neuron;insight;Intellectual functioning disability;Interneurons;Intervention;Knock-out;Knowledge;Measurement;Measures;Mediating;Messenger RNA;Molecular;mouse model;multi-electrode arrays;Mus;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;Neocortex;network dysfunction;Neurons;Neurotransmitter Receptor;new therapeutic target;novel therapeutics;Parvalbumins;patch clamp;pharmacologic;Phase;Phenotype;Predisposition;Process;protein expression;Proteins;Quantitative Reverse Transcriptase PCR;Regulation;Reporting;Research;response;Rest;Role;Seizures;Sensory;sensory cortex;sensory mechanism;sensory stimulus;Slice;Social Behavior;Somatosensory Cortex;Stimulus;Synapses;targeted treatment;Testing;therapeutic development;therapeutic target;Tuberous Sclerosis;Up-Regulation;Western Blotting

PROJECT_TITLE: Examining the role of specific NMDA receptor subunits in cortical circuit dysfunction in Fragile X Syndrome


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Immunotherapy;Precision Medicine;Skin Cancer

PHR: PROJECT NARRATIVE: PROJECT 1 Melanoma is an aggressive skin cancer for which immunotherapy has been successful in an increased fraction of patients—but there remains a critical need to improve upon this, and to understand why many patients are still non-responsive. LAG3 limits effector T cell function and LAG3 blockade exhibits synergy with anti-PD1 in mouse models of cancer, and thus is a logical therapeutic target to increase anti-tumor immunity in combination with anti-PD1. There are now >10 LAG3-targeting therapeutic clinical trials in the US, and yet we still know very little about how LAG3 blockade, alone or in combination with anti-PD1, impacts the immune response to cancer, and whether biomarkers exist which could predict responsiveness.

PI_NAMEs: VIGNALI, DARIO AA (contact)

PROJECT_TERMS: Aftercare;anti-PD-1;anti-PD1 therapy;arm;Biological Markers;biomarker identification;Biopsy;Blinded;Blood;cancer imaging;cancer infiltrating T cells;Cancer Model;Cancer Patient;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cell surface;Cells;Cessation of life;Clinical;Clinical Trials;cohort;Combination immunotherapy;Combined Modality Therapy;Cytometry;effector T cell;Enrollment;Exhibits;Functional disorder;Genetic Transcription;Goals;Homeostasis;IL6 gene;Immune;immune resistance;Immune response;Immune System Diseases;Immunotherapeutic agent;Immunotherapy;improved;innovation;insight;interest;liquid crystal polymer;Malignant Neoplasms;Mediating;Melanoma;Melanoma patient;Metalloproteases;Metastatic Melanoma;Modality;Molecular;mouse model;nano-string;Nivolumab;novel;NRP1 gene;Pathway interactions;patient population;patient response;Patient-Focused Outcomes;Patients;PD-1 blockade;PD-1/PD-L1;Peripheral;peripheral blood;Phase;Phase II Clinical Trials;Phenotype;Plasma;predicting response;Prognosis;programmed cell death protein 1;programs;Proliferating;PTPRC gene;randomized, clinical trials;receptor;receptor expression;Regimen;Regulation;Resistance;resistance mechanism;response;response biomarker;Series;Signal Transduction;single-cell RNA sequencing;Skin Cancer;spectrograph;standard of care;synergism;T cell receptor repertoire sequencing;T-Cell Activation;T-Cell Proliferation;T-Lymphocyte;targeted treatment;Testing;Therapeutic Clinical Trial;therapeutic target;Tissues;tocilizumab;trial design;tumor;Tumor Immunity;tumor microenvironment;Tumor-Infiltrating Lymphocytes

PROJECT_TITLE: Project 1: Evaluating the synergy of LAG3 and PD-1 in melanoma patients


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: Cirrhosis is a major and rising clinical problem in VA due to the high prevalence of risk factors for cirrhosis such viral hepatitis B and C, alcoholic liver disease, obesity, diabetes and fatty liver disease, which has reached epidemic proportions. There are 73,331 patients with cirrhosis currently in VA care, who have high mortality, morbidity, hospitalization and resource utilization rates. Veterans with cirrhosis frequently require surgery, which carries very high risks, especially in those patients with more advanced cirrhosis and liver dysfunction. The proposed C-SuRC will address a major gap in cirrhosis care by providing accurate preoperative risk assessment for Veterans with cirrhosis. C-SuRC estimates will apply directly to Veterans, since C-SuRC will be developed using data from a representative Veteran population. We will develop web-based and app-based tools to execute C-SuRC, which will be used by clinicians for the preoperative assessment of VA patients with cirrhosis who require surgery.

PI_NAMEs: IOANNOU, GEORGE  (contact)

PROJECT_TERMS: Alcoholic Liver Diseases;Algorithms;Black Box;Calibration;Cardiovascular system;Caring;Characteristics;Cirrhosis;Clinic;Clinical;clinical application;comorbidity;Compensation;Complex;Data;Data Set;design;Development;Diabetes Mellitus;Discrimination;Epidemic;explainable artificial intelligence;fatty liver disease;Feedback;Functional disorder;gradient boosting;Healthcare Systems;Hepatic;Hepatitis B;Hepatitis C;High Prevalence;high risk;Hospitalization;Impairment;Improve Access;improved;improved outcome;Individual;individual patient;innovation;instrument;Linear Models;Liver Dysfunction;Logistic Regressions;machine learning algorithm;machine learning method;machine learning model;machine learning prediction;machine learning prediction algorithm;Medical;Methods;military veteran;Modeling;modifiable risk;Morbidity - disease rate;mortality;mortality risk;novel;Obesity;Online Systems;Operative Surgical Procedures;Patient Selection;Patients;Performance;perioperative mortality;Population;Portal Hypertension;Postoperative Period;Predictive Analytics;predictive modeling;Prevalence;prevent;Process;programs;prospective;Reporting;Resources;Risk;Risk Assessment;Risk Factors;risk prediction;risk prediction model;Series;Structure;surgery outcome;surgical risk;Testing;tool;Trees;United States Department of Veterans Affairs;user centered design;Validation;Veterans;Veterans Health Administration

PROJECT_TITLE: Development and Validation of a Cirrhosis-specific Surgical Risk Calculator (C-SuRC)

STUDY_SECTION_NAME: HSR-3 Healthcare Informatics[HSR3]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: Princeton

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: NARRATIVE We will create a Genome Data Analysis Center (GDAC) to analyze data from cancer genome sequencing projects. Our center will develop and apply novel computational approaches to identify biological pathways that are altered in cancer and to characterize tumor heterogeneity, suggesting new approaches for cancer diagnosis and treatment.

PI_NAMEs: RAPHAEL, BENJAMIN  (contact);YEH, JEN JEN

PROGRAM_OFFICER_NAME: YANG, LIMING

PROJECT_TERMS: Address;Algorithms;alternative treatment;analysis pipeline;Area;Biological;cancer cell;cancer diagnosis;cancer genome;cancer genomics;Cancer Patient;cancer therapy;cancer type;Cancerous;cell type;Cells;Clinical;clinical phenotype;clinical predictors;Cloud Computing;Code;cohort;Collaborations;Collection;Communities;Complex;Computer software;Computing Methodologies;Data;data integration;Development;Drug resistance;Epigenetic Process;epigenetic profiling;epigenomics;Evolution;exceptional responders;exome sequencing;experience;Gene Expression;Genome;Genome Data Analysis Center;Genome Data Analysis Network;genome sequencing;genomic data;Genomics;Inter-tumoral heterogeneity;International;Intervention;Knowledge;Malignant Neoplasms;Measurement;Molecular;Mutation;Neoplasm Metastasis;neoplastic cell;Normal Cell;novel;novel strategies;novel therapeutics;Nucleotides;open source;Outcome;Pathway Analysis;Pathway interactions;Patients;Phenotype;Phylogeny;Proteins;Research;response;Signal Transduction;single cell sequencing;single-cell RNA sequencing;spatiotemporal;Technology;The Cancer Genome Atlas;Time;transcriptome;transcriptomic profiling;transcriptomics;Translations;treatment strategy;tumor;tumor growth;tumor heterogeneity;tumor microenvironment;tumor progression;Tumor Promotion;Untranslated RNA;whole genome;Work

PROJECT_TITLE: Pathway, Network and Spatiotemporal Integration of Cancer Genomics Data


ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: NARRATIVE – OVERALL With an estimated 22,000 new cases and 14,000 deaths each year, cancer of the ovary, fallopian tube or peritoneum (termed “ovarian cancer” in this application) remains the most lethal of the gynecological malignancies. The Mayo Clinic SPORE in Ovarian Cancer provides support for translational research projects that are intended to have a rapid impact for ovarian cancer patients. Specifically, we will develop and test four novel therapeutic approaches designed to i) stimulate the immune system (Project 1), ii) introduce a Next Generation TOP1 inhibitor for ovarian cancer (Project 2), iii) repurpose the FDA-approved kinase inhibitor ceritinib as an ovarian cancer therapeutic (Project 3) and iv) provide a new form of adoptive immune cell therapy (Project 4).

PI_NAMEs: KAUFMANN, SCOTT H (contact)

PROGRAM_OFFICER_NAME: BASA JANAKIRAM, NAVEENA

PROJECT_TERMS: Acceleration;Adjuvant;Adoptive Immunotherapy;Allogenic;Animal Model;anti-cancer research;Basic Science;Biochemical;Bioinformatics;Biological;Biometry;Biostatistics Core;Cancer Biology;Cancer cell line;Cancer Model;Cancer Patient;cancer therapy;Cancer Therapy Evaluation Program;career;cellular engineering;Cellular immunotherapy;Cessation of life;chimeric antigen receptor natural killer cells;Clinic;Clinical;Clinical Trials;Clinical Trials Cooperative Group;Collaborations;Complementary DNA;Data;Dendritic Cell Vaccine;Dendritic Cells;design;Development;Disease;DNA Repair Pathway;effective therapy;Enrollment;Epithelial ovarian cancer;FDA approved;follow-up;FOLR1 gene;Fostering;Funding;Future;Generations;Genes;Genomics;Goals;Grant;Homing;homologous recombination;homologous recombination deficiency;Immune;Immune response;Immune system;Immunologic Stimulation;Immunotherapy;improved;inhibitor;innovation;insight;kinase inhibitor;Leadership;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of ovary;Mammalian Oviducts;Mediating;Mentors;Metformin;Methods;Minnesota;Mission;Mitochondria;mortality;mTOR Inhibitor;Natural Killer Cells;next generation;novel;novel therapeutic intervention;novel therapeutics;Organ;Ovarian;Pathway interactions;patient derived xenograft model;patient registry;Patients;Peer Review;Peptides;peritoneal cancer;Peritoneum;phase 1 study;Phase I Clinical Trials;phase I trial;phase II trial;Phenotype;Physiologic pulse;Pilot Projects;Platinum;Poly(ADP-ribose) Polymerase Inhibitor;pre-clinical;programs;Publications;Reactive Oxygen Species;Recurrence;Relapse;Research;research clinical testing;Research Personnel;Research Project Grants;Resistance;Resources;Respiration;safety testing;Serous;Signal Transduction;Survival Rate;taxane;Techniques;Testing;Therapeutic;Therapeutic Agents;Therapeutic Studies;Therapeutic Trials;TOP1 gene;transcriptomics;translational pipeline;Translational Research;translational research program;translational scientist;treatment response;tumor;tumor microenvironment;United States National Institutes of Health;Universities;vaccine response;vaccine strategy;Vaccines;women's treatment

PROJECT_TITLE: Mayo Clinic Ovarian Cancer SPORE


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Mental Health;Mental Illness;Neurosciences;Pediatric;Sleep Research;Telehealth

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Project Narrative Depression in adolescence is growing public health concern, with symptoms beginning as early as pre- adolescence, and conferring heightened risk for long-term deleterious psychological and cognitive outcomes. The purpose of this K08 proposal is to prepare this applicant for a career in translational pediatric research, by investigating the effects of insufficient sleep and depression on longitudinal sleep-dependent hippocampal memory trajectories across the adolescent transition in typical and depressed youth. The knowledge gained from this proposal will address a critical gap in our fundamental knowledge of the individual trajectories of and longitudinal associations between insufficient sleep, depression, and sleep-dependent hippocampal memory across the adolescent transition, and help to identify key timepoints for sleep-based interventions for mental health and cognition across this neurocognitive sensitive period.

PI_NAMEs: SIMON, KATHARINE  (contact)

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TERMS: 12 year old;Address;Adolescence;Adolescent;Affect;Age;age acceleration;Attention;Beds;Brain;career;child depression;Childhood;Circadian Rhythms;Clinical;Clinical assessments;clinical investigation;Clinical Psychology;Cognition;Cognitive;cognitive neuroscience;cognitive testing;Data;Depressed mood;depressive symptoms;design;Development;diaries;Disease;Doctor of Philosophy;Early Diagnosis;early onset;Ecological momentary assessment;Equation;Evaluation;Future;Goals;Growth;Hippocampus;human old age (65+);Individual;Intervention;K-Series Research Career Programs;Knowledge;longitudinal design;Measurement;Measures;Mediation;Memory;Memory impairment;Mental Depression;Mental Health;Mentors;Methods;mHealth;Mobile Health Application;Modeling;multilevel analysis;Neurocognitive;novel;Outcome;Participant;Pediatric Research;Performance;poor sleep;Population;preadolescence;prospective;psychologic;Psychopathology;Public Health;recruit;remote grading;Reporting;Research;Research Domain Criteria;Risk;Risk Factors;Role;Sampling;Scientist;single episode major depressive disorder;skill acquisition;Sleep;Sleep Architecture;Sleep Deprivation;sleep onset;sleep pattern;social relationships;spatial memory;Symptoms;Testing;Time;Training;translational scientist;United States;verbal;wearable device;Youth

PROJECT_TITLE: The role of insufficient sleep and depression on hippocampal-dependent memory trajectories across the adolescent transition

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Biobehavioral and Behavioral Sciences Study Section[CHHD-H]


NIH_SPENDING_CATS: Cancer;Ovarian Cancer;Rare Diseases;Women's Health Research

PHR: NARRATIVE – ADMINISTRATIVE CORE The Administration Core provides the organizational infrastructure necessary to perform the work proposed in this SPORE application.

PROJECT_TERMS: Advisory Committees;Advocate;career;Clinic;Clinical Management;Clinical Trials;Collaborations;Collection;Communication;Communities;design;Detection;Development;Disease;Funding;Goals;Infrastructure;innovation;Leadership;Malignant neoplasm of ovary;Malignant Neoplasms;Mayo Clinic Cancer Center;meetings;member;Methods;Minority;Monitor;Occupational activity of managing finances;Ovarian;Patient advocacy;Performance;Population Research;Prevention;Procedures;programs;Progress Reports;recruit;Reporting;Research;research and development;Research Personnel;Research Project Grants;research study;Research Support;Structure;Translational Research;Translations;Woman;Work

PROJECT_TITLE: Administration Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Skin Cancer

PHR: Project 3: Project Narrative This project evaluates a novel combination immunotherapy approach applicable to a broad range of accessible skin cancers. Specifically, we will target both a potent chemotherapeutic agent to induce immunogenic cell death and an innate immune stimulant specifically to the 3D space of the tumor microenvironment of cutaneous squamous cell carcinomas. These studies represent the first tumor immunotherapy clinical trials utilizing localized spatially and kinetically controlled delivery of a synergistically acting combination therapy.

PI_NAMEs: FALO, LOUIS D (contact)

PROJECT_TERMS: 3-Dimensional;Adverse effects;Agonist;anti-PD1 antibodies;Antigen-Presenting Cells;Antigens;Autoimmune Diseases;Biotechnology;cancer cell;cancer therapy;CD8-Positive T-Lymphocytes;Cell Death;Cells;chemotherapeutic agent;chemotherapy;Chronic;Clinical;clinical application;clinical efficacy;Clinical Trials;cohort;Combination immunotherapy;Combined Modality Therapy;Cutaneous T-cell lymphoma;Data;Development;Devices;Dose;Doxorubicin;Drug Delivery Systems;Epitope spreading;FDA approved;fitness;flexibility;Future;Generations;Goals;Heterogeneity;Immune;Immune checkpoint inhibitor;immune clearance;immune modulating agents;Immune response;immune stimulant;Immunity;Immunocompetent;immunogenic;immunogenic cell death;immunosuppressed;Immunosuppression;Immunotherapy;immunotherapy clinical trials;improved;In Situ;Inflammatory;Injections;Kinetics;Laboratories;local drug delivery;Malignant Neoplasms;Melanoma;Needles;neoplasm immunotherapy;neoplastic cell;next generation;novel;novel therapeutic intervention;Organ Transplantation;Pathologic;Pathway interactions;patient population;Patients;Performance;peripheral blood;Pharmaceutical Preparations;Phase Ib/II Clinical Trial;Positioning Attribute;pre-clinical;preclinical study;prevent;programs;Recurrence;response;Risk;Safety;safety study;Skin;Skin Cancer;Skin Neoplasms;skin squamous cell carcinoma;Solid;Solid Neoplasm;Source;Stimulator of Interferon Genes;T-Lymphocyte;Technology;Therapeutic immunosuppression;Toxic effect;Translating;Transplant Recipients;Transplantation;tumor;Tumor Antigens;tumor eradication;tumor heterogeneity;Tumor Immunity;tumor microenvironment;virtual;Work

PROJECT_TITLE: Project 3: Localized microneedle-directed combination immunotherapy for cSCC


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Bipolar Disorder;Brain Disorders;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Mental Health;Mental Illness;Racial and Ethnic Minority Health Research;Serious Mental Illness

ORG_DEPT: PSYCHIATRY

PHR: PROJECT NARRATIVE This proposal will leverage the Asian Bipolar Genetics Network (A-BIG-NET), an international collaboration of investigators from the U.S., Taiwan, South Korea, Singapore, India and Pakistan, to carry out a molecular genetics study of bipolar disorder in East and South Asia. It will establish a valuable genetics resource with 4x low-pass whole genome sequence and rich phenotype data that will dramatically increase the worldwide diversity of genetics data on bipolar disorder, an important step to accelerate gene discovery in this disorder and advance global mental health equity.

PI_NAMEs: KENDLER, KENNETH SEEDMAN (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Acceleration;Adopted;Adult;Alleles;Asia;Asian;Asian Americans;Asian ancestry;Asian population;Bipolar Disorder;causal variant;Clinical;cohort;Collaborations;comparative;Complement;Consensus;Country;Data;data archive;data collection site;Disease;disorder subtype;DNA;East Asian;Environmental Risk Factor;environmental stressor;Equity;European;European ancestry;experience;field study;Funding;gene discovery;Gene Frequency;Genetic;genetic architecture;genetic association;Genetic Diseases;Genetic Research;genetic resource;genetic risk factor;genetic signature;Genetic study;genetic variant;Genetic Variation;genome sequencing;genomic data;genomic locus;Genomics;Genotype;health disparity;health equity;India;insight;International;Joints;Maps;Measures;Mental disorders;Mental Health;Modeling;Molecular;Molecular Genetics;National Institute of Mental Health;Nature;neuropsychiatric disorder;novel;Outcome;Pakistan;Pathogenesis;Phenotype;phenotypic data;Play;pleiotropism;polygenic risk score;Population;Prevalence;Procedures;Process;Production;Protocols documentation;psychiatric genomics;psychogenetics;Public Health;Publications;Quality Control;rare variant;Records;recruit;Reduce health disparities;Reporting;Research;Research Personnel;Research Project Grants;Resources;Role;Sampling;Sampling Studies;Schizophrenia;severe psychiatric disorder;Singapore;Site;South Asian;South Korea;Taiwan;Time;Uncertainty;Variant;web portal;whole genome;Work

PROJECT_TITLE: 2/4 Asian Bipolar Genetics Network (A-BIG-NET)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-B(60)C]


ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE: Overall Understanding how and which colorectal pre-cancers have the potential to progress to cancer will enable improvements in risk stratification, precision prevention, and interception for individuals with colorectal pre- cancers to prevent colorectal cancer deaths. This research center will seek to identify microbial, stem cell, and cell-cell communication mechanisms that will inform which pre-malignant lesions progress and which will remain indolent.

PI_NAMEs: LAU, KEN S;SHRUBSOLE, MARTHA J. (contact)

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: adenoma;Antigen Presentation;Atlases;base;Basic Science;Big Bang Cosmology;Binding;Biological;Biological Models;Biological Process;Biological Sciences;Biometry;Cancer Biology;Cancer Etiology;Carcinoma;Cell Communication;Cell Line;Cell surface;Cells;Cellular biology;Cessation of life;Chemoprevention;Clinical Data;Clonal Expansion;Coculture Techniques;Collaborations;Colon;colon carcinogenesis;Colonic Neoplasms;Colonoscopy;Colorectal;Colorectal Adenoma;colorectal cancer prevention;Computational algorithm;Computational Biology;cost effective;cytotoxic;Cytotoxic T-Lymphocytes;Data;Data Analyses;design;Detection;Development;Dipeptidases;Dipeptides;disease model;Elements;Epidemiology;Epithelial Cells;Epithelium;Escherichia coli;Evolution;exosome;Exposure to;extracellular vesicles;Gastric Metaplasia;Generations;Genetic;Genotoxic Stress;Goals;Health system;high risk;Human;human data;human tissue;Immune;Immune system;Immunofluorescence Immunologic;immunoregulation;improved;in vitro Model;in vivo Model;Individual;individualized prevention;Indolent;innovation;Investigation;iterative design;Joints;Knowledge;Lead;Lesion;Longitudinal cohort;Malignant Neoplasms;Manuscripts;men;microbial;Microbiology;microbiota;Modeling;Molecular;molecular phenotype;Mucous Membrane;multidisciplinary;multiplexed imaging;Mutagens;Nature;neoplastic cell;neutrophil;next generation;novel;Organoids;Pathology;Pathway interactions;Perforation;polyketide synthase;Polypectomy;Polyps;premalignant;pressure;prevent;Preventive;Process;programs;Prospective Studies;protein biomarkers;Proteins;Reporting;Research;Research Personnel;Research Project Grants;Resources;Risk;risk stratification;Science;Seminal;Shapes;Side;single-cell RNA sequencing;Specialized Program of Research Excellence;stem cells;stemness;Surface;System;Systems Biology;Technology;Testing;Tissues;transcriptomics;Translational Research;tumor;tumor heterogeneity;tumor microenvironment;tumor-immune system interactions;tumorigenesis;United States;Woman;Work

PROJECT_TITLE: Shaping of the Microenvironment in Colonic Pre-Cancer by Epithelia and Microbiota


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Orphan Drug;Ovarian Cancer;Prevention;Rare Diseases;Women's Health Research

PHR: NARRATIVE—BIOSPECIMENS AND PATIENT REGISTRY CORE (CORE B) Biospecimens (tissues, blood, DNA, RNA, and novel biospecimens) from women with ovarian, fallopian tube,  and primary peritoneal cancer as well as women without cancer (average-risk and high-risk for ovarian cancer)  are banked through this Core for current and future use in research projects designed to improve the risk  assessment, prevention, detection and treatment of ovarian cancer. The Biospecimens and Patient Registry  Core (Core B) supports the prospective collection of the spectrum of biospecimens as well as the abstraction  of clinical data from the medical records of women who give their written consent to donate these materials for  research.

PI_NAMEs: SHERMAN, MARK E (contact)

PROJECT_TERMS: Animal Model;anti-cancer research;Antibodies;Archives;Ascites;Back;Benign;Bioinformatics;Biological Assay;Biological Markers;Biometry;Biopsy;Blood;blood product;brca gene;Cancer Center;Cancer Patient;Cancer Research Project;cancer therapy;Cancer-Predisposing Gene;Carcinoma;Cell Line;Cells;chimeric antigen receptor;chimeric antigen receptor natural killer cells;Classification;Clinic;Clinical;Clinical Data;Clinical Trials;cohort;Collaborations;Collection;Communities;Confidentiality of Patient Information;Consent;Cytogenetics;Data;Data Analyses;data management;Data Set;Databases;Dedications;Dendritic Cell Vaccine;design;Detection;Development;digital imaging;DNA;Ethics;Evaluation;Fluorescent in Situ Hybridization;follow-up;Freezing;Funding;Future;Generations;Genes;Genomics;Germ Lines;Goals;Grant;high risk;histological slides;Histology;immune cell infiltrate;Immunohistochemistry;improved;In Situ Hybridization;Informed Consent;Institution;Ions;Link;Maintenance;Malignant - descriptor;Malignant neoplasm of ovary;Malignant Neoplasms;Mammalian Oviducts;Mayo Clinic Cancer Center;Medical Records;member;Morphology;MSLN gene;Natural Killer Cells;Neoplasm Circulating Cells;Normal tissue morphology;novel;Operative Surgical Procedures;Organoids;Outcome;Ovarian;ovarian neoplasm;Paraffin;Paraffin Embedding;participant enrollment;Pathologic;Pathology;patient derived xenograft model;Patient Recruitments;patient registry;Patients;Performance;Peripheral Blood Mononuclear Cell;Peritoneal;peritoneal cancer;Phase;Phase Ib Clinical Trial;Phase II Clinical Trials;Play;Pre-Clinical Model;Prevention;programs;prospective;Proteins;Quality Control;Questionnaires;RAD51C gene;Records;recruit;Research;Research Personnel;Research Project Grants;Research Support;Resource Sharing;Resources;Risk;Risk Assessment;Risk Factors;RNA;Role;Sampling;Serum;Services;Site;Slide;sound;Specimen;Stains;Standardization;stem cells;Surveys;Time;time use;Tissue Banks;Tissue Embedding;Tissue Microarray;tissue registry;Tissues;TOP1 gene;Translational Research;tumor;Tumor Tissue;vaccine trial;Woman;Writing;Xenograft procedure

PROJECT_TITLE: Biospecimens and Patient Registry


PHR: NARRATIVE: Developmental Research Program (DRP) The Developmental Research Program (DRP) of the MSCP SPORE will solicit, identify and support innovative high-risk, high-reward pilot research in melanoma and skin cancer, with intent to develop mature projects worthy of extramural support (including SPORE rebid efforts). Submissions from investigators new to this field and high-risk, high-gain proposals will be strongly encouraged.

PI_NAMEs: STORKUS, WALTER J. (contact)

PROJECT_TERMS: Advocate;Applications Grants;Area;Award;Basic Science;Biological Response Modifier Therapy;broadening participation research;Cancer Center;cancer therapy;Clinic;Clinical;Clinical Research;Collaborations;Communities;Comprehensive Cancer Center;Data;Development;Eligibility Determination;Extramural Activities;Feedback;Funding;Future;Goals;Grant;high reward;high risk;Immunotherapy;innovation;Institution;International;meetings;Melanoma;member;Mentors;novel;Ohio;Patients;Peer Review;Pilot Projects;Preparation;Process;Program Research Project Grants;programs;Publications;recruit;Research;Research Personnel;Research Support;Resources;Roswell Park Cancer Institute;Services;Skin Cancer;Source;symposium;System;Time;Translational Research;Translations;United States National Institutes of Health;Universities;working group

PROJECT_TITLE: Developmental Research Program


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Breast Cancer;Cancer;Digestive Diseases;Genetics;Liver Cancer;Liver Disease;Rare Diseases;Women's Health Research

ORG_DEPT: GENETICS

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Aberrant transcription of protein-encoding genes by RNA polymerase II is a cause of many human diseases, especially cancer. Pol II(G), a metazoan-specific form of Pol II, plays an essential role in embryonic development, while in quiescent differentiated cells, Pol II(G) is dispensable for viability but critical for maintenance of tissue-specialized functions. This proposal will reveal new insights into biological and mechanistic aspects of Pol II(G), and will further assess how modulation of its function impacts transcription in breast and hepatocellular carcinomas, thereby suggesting potential therapeutic avenues.

PI_NAMEs: ROEDER, ROBERT G (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: Ablation;Acute;Albumins;Binding;Biochemical;Biological;Biological Assay;Breast Cancer Cell;Breast Carcinoma;cancer cell;Cancer Cell Growth;Carcinoma;Cell Cycle;Cell Differentiation process;cell growth;Cell Line;Cells;ChIP-seq;Chromatin;Cleavage Under Targets and Release Using Nuclease;cofactor;Complement;Complex;Cryoelectron Microscopy;Development;Down-Regulation;Elongation Factor;Embryo;Embryonic Development;Enhancers;Event;Experimental Designs;fly;Gene Activation;gene repression;Genes;Genetic;Genetic study;Genetic Transcription;Growth;Hep3B;Hepatocarcinogenesis;Hepatocyte;Human;human disease;Immobilization;In Vitro;Individual;insight;Intervention;lipid metabolism;Liver;liver development;Maintenance;Malignant Breast Neoplasm;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Mediator;Modeling;Molecular Mechanisms of Action;Mouse Embryonic Stem Cells;multiple omics;Mus;negative elongation factor;novel;p53 Signaling Pathway;Pathology;Peptide Initiation Factors;Physiological;Physiological Processes;Play;Polymerase;polypeptide;premalignant;prevent;Primary carcinoma of the liver cells;Process;Productivity;programs;promoter;Property;Proteins;Recombinants;reconstitution;recruit;Regulation;Repression;RNA Polymerase II;Role;Signal Pathway;Site;Structure;Therapeutic;Tissues;TP53 gene;Transcription Coactivator;Transcription Elongation;transcription factor;transcription factor S-II;Transcription Factor TFIIB;transcription factor TFIIF;Transcription Initiation;Transcriptional Elongation Factors;Transcriptional Regulation;Variant;Yeasts

PROJECT_TITLE: Mechanistic studies of transcription initiation and elongation functions of an RNA polymerase II variant, Pol II(G), that is implicated in development and cancer

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Bioengineering;Cancer;Ovarian Cancer;Rare Diseases;Women's Health Research

PHR: PROJECT NARRATIVE – BIOSTATISTICS AND BIOINFORMATICS CORE (CORE C) The Ovarian SPORE Biostatistics and Bioinformatics Core collaborates with SPORE investigators in designing studies and clinical trials, determining optimal data collection methods, performing data management and quality control, and in analyzing and interpreting study results. The Biostatistics and Bioinformatics Core interacts with the other three Ovarian SPORE Cores, ensuring optimal use of resources and outstanding quality research.

PI_NAMEs: OBERG, ANN LAURA (contact)

PROJECT_TERMS: analytical tool;Animal Model;Archives;Basic Science;Bioinformatics;Biometry;career;Clinic;Clinical;Clinical Sciences;Clinical Trials;Collaborations;Country;Data;Data Analyses;Data Collection;data infrastructure;data management;Data Management Resources;data quality;data sharing;Database Management Systems;Databases;design;Development;Ensure;experience;Experimental Designs;improved;Informatics;Infrastructure;innovation;Institution;instrumentation;Malignant neoplasm of ovary;Manuscripts;Measurement;member;Methods;migration;Monitor;Ovarian;patient derived xenograft model;patient registry;Patients;Preparation;Procedures;programs;Quality Control;Randomized;Registries;Reporting;Reproducibility;Research;Research Design;Research Methodology;Research Personnel;research study;Resources;Safety;Sample Size;Scheme;sound;Source;study population;System;Testing;Time;tool

PROJECT_TITLE: Core C:  Biostatistics and Informatics


NIH_SPENDING_CATS: Cancer;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prostate Cancer;Racial and Ethnic Minority Health Research;Social Determinants of Health;Urologic Diseases

ORG_CITY: NEW ORLEANS

ORG_DEPT: UROLOGY

ORG_NAME: LSU HEALTH SCIENCES CENTER

ORG_STATE: LA

PHR: In African American (AA) men prostate cancer is characterized by higher aggressiveness, early onset, more extensive metastases, and increased mortality rates compared to those in Caucasian men. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is no effective treatment for intervention in metastatic prostate cancer. Currently-used prognostic indicators (Digital rectal exam, PSA measurement and Gleason score) do not predict metastases risk accurately. These facts underline the urgent, yet unmet, need for identification and characterization of new targets that can help distinguish between aggressive and metastatic prostate cancer from an indolent disease. Our goal is to address this vital knowledge gap by characterizing the role of Prostate Derived Ets Transcription Factor (PDEF) in PCa aggressiveness, thereby reducing the prostate cancer-related health disparity between African American (AA) and Caucasian men. We propose a novel and unique causative link between PDEF and metastases. Our proposal also details mechanistic experiments that may help to patient stratification and use PDEF expression as a means to stratify patients to demethylating agents. Our studies will pave the way for routine clinical use of PDEF as an independent predictor of metastases risk.

PI_NAMEs: KOUL, HARI K (contact)

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: Address;African American;Animal Model;anti-cancer research;Azacitidine;Behavior;Biological Models;cancer health disparity;Castration;Caucasians;Cell Culture Techniques;cell motility;Cells;Clinical;Clinical Data;conventional therapy;Data;Data Set;Death Rate;Decitabine;demethylation;Development;digital;Disease;Disease Outcome;DNA;DNA Methylation;DNA Methyltransferase Inhibitor;Early Diagnosis;early onset;effective therapy;enzalutamide;epigenetic regulation;ethnic disparity;experimental study;Future;Genes;Genetic Transcription;Gleason Grade for Prostate Cancer;Goals;Growth;health disparity;in vitro activity;in vivo;in vivo Model;Indolent;inhibitor;innovation;Intervention;Invaded;Investigation;knock-down;Knowledge;Link;Malignant neoplasm of prostate;Malignant Neoplasms;Measurable;Measurement;men;Metastatic Prostate Cancer;Methods;Methylation;Micrometastasis;Mission;Modeling;Molecular;Morbidity - disease rate;mortality;mRNA Expression;Mus;Neoplasm Metastasis;novel;Pathologic;Pathway interactions;patient stratification;Patient-Focused Outcomes;Patients;Phenotype;prognostic indicator;promoter;Prostate;prostate cancer cell;prostate cancer metastasis;Prostate Cancer therapy;protein expression;racial disparity;Rectum;Resistance;Risk;Role;Sampling;Signal Transduction;Specimen;Testing;tibia;Tissues;tool;transcription factor;Transferase;Treatment outcome;tumor;tumor xenograft;TWIST1 gene;United States National Institutes of Health

PROJECT_TITLE: Prostate Cancer Health Disparity: Role of PDEF

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-B(55)R]


PHR: NARRATIVE: Career Enhancement Program (CEP) The CEP of the MSCP SPORE will solicit, identify and support investigators new to research in melanoma and skin cancer with both pilot study funding and expertise and assistance in the planning and preparing grant applications for independent funding. This program builds on a previous successful 10-year track record of faciliating the career advancement of young investigators in the field of melanoma and skin cancer research and the evolution of their CEP-sponsored studies into mature projects funded via extramural grant agencies and the replenishment of SPORE component projects (as in the case of Projects 1 and 2 in the current renewal application).

PROJECT_TERMS: Advocate;anti-cancer research;Applications Grants;Appointment;Area;Award;Basic Science;Biological Response Modifier Therapy;broadening participation research;Cancer Center;cancer therapy;career;Career Mobility;Clinic;Clinical;Clinical Research;Collaborations;Development;Eligibility Determination;Environment;Evolution;experience;Extramural Activities;Feedback;Female;Foundations;Funding;Future;Goals;Grant;Immunotherapy;Industry;innovation;Institution;instructor;Leadership;Malignant Neoplasms;Melanoma;member;Mentors;Minority;Mission;Ohio;outreach;Patients;Peer Review;Pilot Projects;Positioning Attribute;Preparation;Process;professor;programs;Publications;Publishing;recruit;Research;Research Assistant;Research Personnel;Resources;role model;Roswell Park Cancer Institute;Services;Site;skills;Skin Cancer;success;symposium;System;Translational Research;Translations;Underrepresented Minority;United States National Institutes of Health;Universities;Work;working group

PROJECT_TITLE: Career Enhancement Program


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

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

ORG_CITY: BERKELEY

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative This project estimates the causal impact of a child health investment on recipients’ long-run life outcomes, as well as on the health and cognitive development of recipients’ children, exploiting experimental variation to overcome the key methodological challenge of confounding. The research builds on the existing Kenya Life Panel Survey (KLPS) longitudinal dataset, which contains detailed information on individual health, education, social attitudes, and labor market outcomes over an exceptionally long timeframe (1998-2021), and will extend this panel dataset through 2026 for 6,500 adults and over 5,000 of their children. The project will estimate the extent to which the child health intervention (deworming) can improve long-run living standards and help break the intergenerational transmission of poverty, and will also assess the effects of two low-cost parent-child interventions (reading promotion and sleep promotion) on child learning and development.

PI_NAMEs: MIGUEL, EDWARD ANDREW (contact)

PROGRAM_OFFICER_NAME: JEKIELEK, SUSAN

PROJECT_TERMS: 13 year old;15 year old;9 year old;Address;Adolescent Development;Adult;Adverse event;Africa South of the Sahara;aged;aspirate;Attitude;Behavior;Behavioral;behavioral outcome;beneficiary;benefit sharing;burden of illness;Child;Child Development;Child Health;Child Rearing;Cognitive;cognitive development;cognitive performance;cognitive testing;Communities;cost;Cost Analysis;cost effectiveness;COVID-19 pandemic;COVID-19 pandemic effects;Data;Data Set;data structure;design;Development;early childhood;Economics;Education;Equilibrium;Event;Fertility;Gender;Grant;Happiness;Health;Home environment;Hour;improved;in utero;Individual;innovation;intergenerational;Intervention;Investments;Job loss;Kenya;Learning;learning outcome;Life;Life Cycle Stages;Living Standards;Long-Term Effects;longitudinal dataset;Longitudinal Studies;Longitudinal Surveys;low and middle-income countries;Marital separation;Marital Status;Marketing;Marriage;Measures;Mental Health;Methodology;migration;mortality;National Institute of Child Health and Human Development;novel;nutrition;Nutritional;Outcome;Parents;Participant;Performance;Personal Satisfaction;Pharmaceutical Preparations;Politics;Poverty;Primary Schools;programs;Randomized;Reading;Reporting;Research;Research Personnel;Respondent;Running;Sampling;School-Age Population;Schools;Shock;Sleep;social;socioeconomics;Structure;Surveys;Testing;Time;transmission process;treatment arm;treatment group;urban residence;Variant;violence exposure

PROJECT_TITLE: Experimental Evidence on Long-run and Intergenerational Impacts of Child Health Investments in the Kenya Life Panel Survey (KLPS)

STUDY_SECTION: SSPB

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


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Cannabinoid Research;Clinical Research;Electronic Nicotine Delivery Systems;Pediatric;Prevention;Substance Misuse;Tobacco

ORG_CITY: Los Angeles

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: ! PROJECT NARRATIVE Vaping—the inhalation of vaporized substances from electronic devices–has increased in adolescents and young adults (AYAs), including vaping of flavors only, nicotine, and cannabis products. This study will provide new essential information about whether low-risk AYAs begin nicotine and cannabis use via vaping, and whether vaping may lead to adverse consequences, including cigarette and cannabis smoking. This study will provide public health officials with data regarding the potential adverse public health impact of AYA vaping and clear targets for intervention to reduce AYA vaping and the health consequences that may follow.

PI_NAMEs: BARRINGTON-TRIMIS, JESSICA LOUISE;LEVENTHAL, ADAM MATTHEW (contact)

PROGRAM_OFFICER_NAME: RODITIS, MARIA LEIA

PROJECT_TERMS: Address;Adolescence;Adolescent and Young Adult;Adverse effects;adverse outcome;Age;Age Months;aged;Anxiety Disorders;Attention deficit hyperactivity disorder;Behavioral;biopsychosocial;California;Cannabinoids;Cannabis;Cannabis policy;catalyst;Characteristics;Chronic;Cigarette;cigarette smoking;cohort;combustible tobacco;Community Health;Data;Data Sources;Dedications;Dependence;design;Development;deviant;Devices;digital;Disease;distress tolerance;Drug abuse;Drug usage;electronic cigarette use;Electronics;emerging adult;Emotional;Expectancy;experience;experimental study;Flavoring;flexibility;follow-up;Friends;Future;habituation;Health;heated tobacco products;high risk;high school;High School Student;high-risk adolescents;Impulsivity;Inhalation;Intervention;JUUL;Left;Link;Malignant Neoplasms;Marijuana Smoking;marijuana use;marijuana vaping;Measures;Mediating;Modeling;Mood Disorders;multiple drug use;Nicotine;nicotine exposure;nicotine use;ninth grade;novel;Oils;Outcome;Participant;Pharmaceutical Preparations;Plants;Play;Policies;Policy Maker;Population;prevent;Prevention;Prevention strategy;Problem behavior;programs;progression risk;Proliferating;Public Health;public health priorities;public policy on tobacco;recruit;Research;Rewards;Risk;Risk Factors;risk prediction;Role;Sampling;Schools;Science;Scientist;Self Administration;Smoking;smoking initiation;social;stem;Students;Surveys;Technology;Testing;THC concentration;Tobacco;tobacco products;Tobacco use;Tobacco-Related Carcinoma;trait;Uncertainty;uptake;vaping;vaping nicotine;Variant;Waxes;young adult;Youth

PROJECT_TITLE: Vaping Nicotine and Cannabis Across Adolescence and Young Adulthood

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Clinical Research;Infectious Diseases;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_CITY: ABUJA

ORG_COUNTRY: NIGERIA

ORG_FIPS: NI

ORG_NAME: INSTITUTE OF HUMAN VIROLOGY

PHR: Project Narrative Akros and Institute Human Virology Nigeria will expand INFORM DS-I Africa to include West African Center for Cell Biology of Infectious Pathogens and pivot an existing GIS platform to geo-enable and strengthen existing malaria genomic surveillance network in Ghana for detecting antimalarial resistance.

PI_NAMEs: ABIMIKU, ALASH'LE G. (contact);AWANDARE, GORDON AKANZUWINE;MICHELO, CHARLES ;WINTERS, ANNA MARIE

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Africa;African;Anti-malarial drug resistance;Anti-malarials;Area;Blood;Cellular biology;Collaborations;Communities;Containment;COVID-19;Data;Data Science;data streams;Decision Making;design;drug efficacy;Dryness;Early Diagnosis;epidemiologic data;Epidemiology;Field Workers;Genetic;genomic data;Genomics;Geography;Ghana;HIV;Household;Human;improved;innovation;insight;Intervention;Investigation;Laboratories;Laboratory Research;Link;Malaria;member;Modeling;Molecular;molecular marker;Monitor;next generation sequencing;Nigeria;open source;pathogen;Patients;Pattern;Pharmaceutical Preparations;Plasmodium;programs;Research;Research Personnel;research study;Resistance;response;Sampling;sociodemographics;spatiotemporal;Spottings;Strategic Planning;surveillance data;surveillance network;System;tool;Translating;Treatment Failure;treatment guidelines;Vaccines;virology;Visualization;Work

PROJECT_TITLE: Geo-enabled detect and respond system for antimalarial resistance in Ghana: GDRS - Ghana

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BTC-L(70)R]


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

PHR: NARRATIVE—ANIMAL MODELS CORE (CORE D) The Animal Models Core (Core D) will facilitate the translation of novel therapies into the clinic by providing SPORE investigators with ovarian cancer patient-derived xenograft (PDX) models in immunocompromised mice, a syngeneic model in immunocompetent mice, and ex vivo 3D cultures of PDX tumors. PDX tumors were collected at surgery from women with ovarian, fallopian tube, and primary peritoneal cancer made available through this Core for current and future use in research projects designed to improve the treatment of ovarian cancer. The Animal Models Core collaborates directly with Core B for tumor acquisition and with Core C for genomic and clinical data correlation.

PI_NAMEs: WEROHA, SARAVUT  (contact)

PROJECT_TERMS: 3-Dimensional;animal care;Animal Experimentation;Animal Model;Animals;anti-cancer research;Ascites;Bioinformatics;Biometry;Breeding;cancer therapy;career;Cell Line;Cells;Characteristics;chimeric antigen receptor natural killer cells;Clinic;Clinical;Clinical Data;clinical practice;clinically relevant;Collaborations;Collection;Communities;Complement;conditioning;Data;Data Correlations;Dendritic Cell Vaccine;design;Development;drug sensitivity;Engraftment;Ensure;Evaluation;experience;experimental study;Female;forging;Fostering;Funding Agency;Future;Gene Expression;Genes;Genetic;genomic data;Genotype;Germ Lines;Goals;Greater sac of peritoneum;Histologic;Human Resources;Immunocompetent;Immunocompromised Host;improved;in vivo;Individual;Injections;investigator training;Laboratory Personnel;Malignant neoplasm of ovary;Mammalian Oviducts;member;Methods;Modeling;Molecular;Monitor;Monoclonal Antibodies;Mus;nanoparticle;Natural Killer Cells;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;Outcome;Ovarian;patient derived xenograft model;patient registry;patient response;Patients;peritoneal cancer;Pharmaceutical Preparations;Pharmacotherapy;Platinum;Production;Program Research Project Grants;programs;Reproducibility;Research Personnel;Research Project Grants;Resources;response;Sampling;SCID Mice;Services;skills;small molecule inhibitor;Source;Standardization;taxane;Testing;Therapeutic;three dimensional cell culture;Tissue Banks;TOP1 gene;Translational Research;Translations;tumor;Tumor Bank;Tumor Volume;tumor xenograft;wasting;Woman;Work;Xenograft procedure

PROJECT_TITLE: Core D:  Animal Models


NIH_SPENDING_CATS: Cancer;Microbiome

PI_NAMEs: SHRUBSOLE, MARTHA J. (contact)

PROJECT_TERMS: Academic Medical Centers;Agreement;Basic Science;Biological Sciences;Cancer Center;Collaborations;Colon;Communication;Data;Data Coordinating Center;data exchange;data sharing;Development;Ensure;Environment;Epithelium;Evaluation;Expenditure;experience;Feedback;Fostering;Funding;Human;human tissue;improved;Infrastructure;Institution;Interdisciplinary Study;Lead;Leadership;Lesion;member;microbiota;Modeling;multidisciplinary;operation;organizational structure;Participant;Play;Policies;premalignant;Procedures;Process;programs;recruit;Regulation;Reporting;Research;research data dissemination;Research Design;Resource Sharing;Role;Science;Secure;Shapes;success;System;Tissue atlas;tool;Translational Research;United States National Institutes of Health;Universities;Vision;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Clinical Research

PHR: Project Narrative The Cellular Senescence Network (SenNet) Consortium Organization and Data Coordination Center (CODCC) will engage the rapidly growing community of single-cell genomics mapping consortia including the Human BioMolecular Atlas Program Consortium (HuBMAP), the Human Cell Atlas (HCA) and the Human Tumor Atlas Network (HTAN). In particular, SenNet focuses on discovery, induction, and mapping of specific physiology at the cellular and molecular level, under a variety of normal, experimental and disease conditions. Investigators among the Consortium Organization and Data Coordination Center (CODCC), Tissue Management Centers (TMCs), and Technology Development (TTDs), as well as the broader community of Cellular Senescence (CS) scientists and innovators, will work together to common purpose to achieve a multiyear strategy of human impact.

PI_NAMEs: BAR-JOSEPH, ZIV ;BLOOD, PHILIP D.;SILVERSTEIN, JONATHAN C. (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Address;Aging;Architecture;Atlases;Back;base;Biological;Biological Assay;Biology;Body System;burden of illness;Cancer Control;Catalogs;Cell Aging;cell community;Cells;Cellular biology;Characteristics;Clinical Data;Collaborations;Communication;Communities;Conceptions;Creativeness;Data;Data Analyses;Data Coordinating Center;data integration;data pipeline;data portal;data sharing;data standards;Dedications;Deterioration;Disease;Educational workshop;Ensure;experience;experimental study;flexibility;Goals;Health;Hearing;Home;Human;Human BioMolecular Atlas Program;Hybrids;Image;improved;Individual;Ingestion;innovation;Institution;interactive visualization;interest;Laboratories;Lead;Leadership;Liquid substance;Malignant Neoplasms;Maps;meetings;Mission;Modernization;Molecular;Mus;Neurologic;novel;open source;Outcome Measure;outreach;Participant;Pathway interactions;Phenotype;Physiology;Publishing;Quality Control;repository;Research Personnel;Resources;Science;Scientist;Secure;Security;Semantics;senescence;senescent cell;Services;single cell genomics;Site;skills;Source;success;System;Technology;technology development;Time;Tissue atlas;tissue mapping;Tissues;tool;tumor;Vision;Visualization;Visualization software;Voice;web portal;Work;working group

PROJECT_TITLE: Cellular Senescence Network (SenNet) Consortium Organization and Data Coordinating Center (CODCC)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-T(71)R]


NIH_SPENDING_CATS: Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Microbiome

PI_NAMEs: COFFEY, ROBERT J. (contact)

PROJECT_TERMS: adenoma;Attention;Behavior;Binding;Biological Assay;Biological Markers;Biological Process;cancer biomarkers;cancer cell;Cell Line;Cells;Cellular biology;Characteristics;Coculture Techniques;Colon;colon cancer cell line;Colonic Adenoma;Colorectal Adenoma;Colorectal Cancer;Communication;Confocal Microscopy;Data;Dipeptidases;Dipeptides;elastase inhibitor;Electrical Resistance;Enzyme-Linked Immunosorbent Assay;Epithelium;exosome;Exposure to;Extracellular Matrix;extracellular vesicles;Flow Cytometry;Future;healthy volunteer;Human;Immune;Immunofluorescence Immunologic;immunoreactivity;In Vitro;in vivo;interest;Invaded;Knock-out;Knowledge;Lesion;Leukocyte Elastase;Malignant neoplasm of pancreas;Malignant Neoplasms;Manuscripts;Mediating;microbiota;Monitor;mouse model;Mus;Nature;Neoplasm Metastasis;neutrophil;Neutrophil Infiltration;Organoids;Patients;Polyps;Population;premalignant;Proliferating;Property;protein biomarkers;Proteins;Reporter;Reporting;repository;Role;Sampling;Selection Criteria;Shapes;Signal Transduction;single-cell RNA sequencing;Source;spatial relationship;Specimen;Stains;stem cells;System;Techniques;Testing;timeline;Tissue Microarray;Tissues;transcriptome sequencing;tumor;tumor microenvironment;tumor progression;Tumor Suppressor Proteins;Western Blotting

PROJECT_TITLE: Shaping the Microenvironment by DPEP1 Facilitates Adenoma Progression


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetic Testing;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Precision Medicine;Prevention;Social Determinants of Health

ORG_CITY: HOUSTON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: NARRATIVE The Great Lakes New England Clinical Validation Center (GLNE CVC), a Clinical Validation Consortium component of the Early Detection Research Network (EDRN) is a highly collaborative group of investigators whose aim is to validate biomarkers for the early detection and risk assessment of cancers of the gastrointestinal tract.

PI_NAMEs: BRESALIER, ROBERT S (contact);SYNGAL, SAPNA

PROGRAM_OFFICER_NAME: YOUNG, MATTHEW R

PROJECT_TERMS: Address;Adenocarcinoma;adenoma;Adherence;Adult;African American population;Age;Archives;Biological Markers;biomarker discovery;biomarker panel;biomarker validation;Blood;blood-based biomarker;candidate marker;circulating biomarkers;Clinic;Clinical;Clinical Data;Collaborations;Colon;Colon Carcinoma;Colonoscopy;Colorectal;Colorectal Cancer;colorectal cancer screening;Colorectal Neoplasms;cost;Development;Diagnostic;DNA;early detection biomarkers;Early Detection Research Network;Early Diagnosis;early onset colorectal cancer;Enrollment;Feces;follow-up;Future;High grade dysplasia;high risk;Incidence;Individual;Industrialization;Institution;Link;Low income;Malignant neoplasm of gastrointestinal tract;Malignant Neoplasms;Methods;Morbidity - disease rate;mortality;Neoplasms;New England;Participant;Patients;Performance;Phase;Plasma;point of care;Population;predictive marker;preservation;Prevalence;Procedures;prospective;Proteins;Research;Research Personnel;response;Risk Assessment;sample collection;Sampling;screening;Serum;sex;Specimen;stool sample;Testing;Tissues;Tubulovillous Adenoma;underserved community;Underserved Population;Urine;Validation;Villous Adenoma


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy;Orphan Drug;Ovarian Cancer;Radiation Oncology;Rare Diseases;Women's Health Research

PHR: PROJECT NARRATIVE: In this application, we focus our research on our new discovery that ARID1A regulates transcriptional silencing and restricts de-repression of heterochromatin repetitive DNA sequences induced by radiation. This new mechanism allows us to augment radiotherapy and immunotherapy through selectively modulating DNA damage(RNA/DNA sensing pathway)-dependent innate immune responses in ARID1A-deficient tumors.

PI_NAMEs: PENG, GUANG  (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: Animal Model;ARID1A gene;Biochemistry;Bioinformatics;Biology;cancer cell;cancer genomics;Cells;Cellular biology;Chromatin Remodeling Factor;clinical application;CRISPR/Cas technology;Cytosine;Data;derepression;DNA;DNA Damage;DNA Methylation;DNA Repair;DNA Sequence;Double-Stranded RNA;effective therapy;Elements;Frequencies;Gene Silencing;Genes;Genetic;Genetic study;Genetic Transcription;genomic data;Goals;Heterochromatin;heterochromatin-specific nonhistone chromosomal protein HP-1;Immune;Immunotherapy;Impairment;improved;in vivo;inhibitor;Innate Immune Response;innate immune sensing;innovation;interdisciplinary approach;Interferons;Ionizing radiation;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Methyltransferase;Molecular;Mutate;Mutation;novel therapeutics;Nucleic Acids;Ovarian Carcinoma;Ovarian Clear Cell Tumor;ovarian neoplasm;Pathway interactions;Patients;Phosphorylation;Phosphotransferases;pre-clinical;programs;Proteomics;Radiation;Radiation exposure;Radiation Induced DNA Damage;radiation resistance;Radiation therapy;Radiosensitization;recruit;Regimen;Research;response;RNA;Role;Sampling;Satellite DNA;Serine;Signal Transduction;Site;small hairpin RNA;Stimulator of Interferon Genes;SWI/SNF Family Complex;Testing;Therapeutic;therapeutically effective;Translating;translational study;tumor;Tumor Immunity

PROJECT_TITLE: Mechanisms of radioresistance and strategies for radiosensitization in ovarian clear cell carcinoma

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Aging;Cancer;Cancer Genomics;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Microbiome;Prevention

PROJECT_TERMS: Acceleration;Address;adenoma;Adoption;Adverse event;Affect;Anesthesia procedures;Automobile Driving;Bacteroides fragilis;Biological Markers;Biological Specimen Banks;Biology;burden of illness;Cancer Etiology;carcinogenesis;Cells;Cessation of life;Characteristics;clinical predictors;cohort;Collaborations;Colon;colon carcinogenesis;colon microbiota;Colonic Neoplasms;Colonoscopy;Colorectal;Colorectal Cancer;colorectal cancer risk;colorectal cancer screening;cost effective;Data;Data Set;design;Detection;Developed Countries;Development;Diet;Disease;Disease stratification;DNA;early onset;Ecosystem;Epidemiology;Epithelial Cells;Epithelium;Escherichia coli;exome sequencing;Fostering;Gene Mutation;Genes;Genomics;Hand;Hemorrhage;Human;human data;Immunofluorescence Immunologic;improved;improved outcome;Individual;Indolent;Induced Mutation;Investigation;Lesion;lifetime risk;longitudinal design;Malignant - descriptor;Malignant Neoplasms;men;microbial;microbiome;microbiota;Modeling;Molecular;molecular marker;Mucous Membrane;Mutagens;Mutate;Mutation;Neoplasms;Obesity;Pathogenesis;Pathway interactions;Perforation;Persons;polyketide synthase;Polypectomy;Polyps;premalignant;Prevention;Prevention strategy;Public Health;Publishing;Recommendation;Reporting;Risk;Risk Factors;risk stratification;Science;screening;Seminal;Shapes;single-cell RNA sequencing;Smoking;Stimulus;Testing;Time;United States;uptake;Virulence;Woman

PROJECT_TITLE: Colibactin-Producing Escherichia coli as an Environmental Stimulus Shaping Pre-Cancer Progression


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Hematology;Human Genome;Immunotherapy;Microbiome;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

PI_NAMEs: LAU, KEN S (contact)

PROJECT_TERMS: adaptive immunity;Algorithms;arms race;Atlases;Big Bang Cosmology;Biological Assay;Biological Models;Cancer Biology;Cell Communication;cell community;Cells;Chromosome Mapping;Clinical;Clonal Expansion;Coculture Techniques;Colon;colon tumorigenesis;Colorectal Cancer;Communication;Complex;Computer Models;CRISPR/Cas technology;cytotoxic;Cytotoxic T-Lymphocytes;cytotoxicity;Data;Development;DNA sequencing;Dysplasia;Ecosystem;Elements;Environment;Epithelium;Event;Evolution;Exhibits;exome sequencing;Genetic;genetic evolution;Genomics;Human;Hyperactivity;Immune;Immune Evasion;Immune system;immunogenic;immunoregulation;Immunosuppression;Immunotherapy;In Vitro;Individual;Intervention;Knowledge;laser capture microdissection;Malignant - descriptor;Malignant Neoplasms;Maps;microbiota;Modeling;Molecular;Monitor;Morphology;multiple omics;multiplexed imaging;Mutation;Myelogenous;Neighborhoods;neoantigens;neoplastic cell;new technology;Organoids;Pathologic;Pathologist;Pathway interactions;patient prognosis;patient response;Patients;Phylogeny;Polyps;predictive modeling;premalignant;pressure;Prevention;reconstruction;response;Sampling;scaffold;Shapes;single cell sequencing;single-cell RNA sequencing;Somatic Mutation;Specimen;stem;stem cells;stemness;System;Systems Analysis;T cell clonality;Technology;Testing;Therapeutic Intervention;transcriptomics;transfer learning;tumor;tumor heterogeneity;tumor progression;Tumor stage;tumor-immune system interactions;tumorigenesis;Work

PROJECT_TITLE: Co-Evolution Mechanisms of Pre-Cancer-Immune Interactions in Shaping Adaptive Cytotoxicity and Myeloid-Derived Suppression


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

PHR: NARRATIVE – PROJECT 2 Treatment options are limited for women whose ovarian cancer has become resistant to platinum drugs and PARP inhibitors. Clinical studies have shown that prolonged schedules of DNA topoisomerase I (TOP1) inhibitors can be effective in some platinum-resistant ovarian cancers. Our preclinical studies have also shown that PARP inhibitors can enhance the antitumor effects of TOP1 inhibitors in vitro and in ovarian cancer patient derived xenograft (PDX) models despite resistance to the antitumor effects of PARP inhibitor alone. These observations, which reflect the fact that PARP inhibition and PARP inhibitor-induced tumor cell killing are related but separable processes, provide the opportunity to use PARP inhibitors as chemosensitizing agents in ovarian cancers that are PARP inhibitor resistant. Accordingly, this project will study the action of a promising 3rd generation ultra- long acting TOP1 inhibitor, PLX038, in combination with the PARP inhibitor rucaparib in preclinical models and in a phase II clinical trial in platinum- and PARP inhibitor-resistant high grade serous ovarian cancer.

PI_NAMEs: KAUFMANN, SCOTT H (contact)

PROJECT_TERMS: ABCG2 gene;Address;Affect;Animal Model;Antibodies;antibody detection;antitumor effect;bevacizumab;Biochemical;Bioinformatics;Biological Markers;Biometry;Biopsy;BRCA1 gene;BRCA1 Mutation;BRCA2 gene;BRCA2 Mutation;Cancer Model;Cancer Patient;cell free DNA;cell killing;Cell Line;Cells;chemosensitizing agent;Clinic;Clinical;clinical practice;Clinical Research;Clinical Trials;cohort;Complex;CRISPR screen;cytotoxicity;design;Development;Diagnostic Reagent;Disease;Disease Resistance;DNA Damage;DNA Repair Enzymes;Dose;drug action;efficacy evaluation;Epithelial ovarian cancer;Excision;Exhibits;Failure;FDA approved;Formulation;Generations;Genes;Genetic;genomic profiles;Genomics;Germ-Line Mutation;homologous recombination;homologous recombination deficiency;improved;In Vitro;in vivo;Infusion procedures;inhibitor;insight;Investigation;irinotecan;Laboratories;Maintenance Therapy;Malignant neoplasm of ovary;Mammalian Oviducts;Marrow;Modeling;Mutation;nanoparticle;Neoplasm Circulating Cells;Neoplasms;neoplastic cell;next generation;NKTR gene;novel therapeutics;Ovarian;overexpression;PARP inhibition;patient derived xenograft model;Patients;peritoneal cancer;Pharmaceutical Preparations;Phase II Clinical Trials;phase II trial;Platinum;Poly(ADP-ribose) Polymerase Inhibitor;Polyethylene Glycols;Polymerase;pre-clinical;Pre-Clinical Model;preclinical study;Process;Prodrugs;Progression-Free Survivals;protein expression;Recurrence;Refractory;Regimen;Relapse;Reporting;Resistance;resistance mechanism;response;Sampling;Schedule;Serous;Site;SN-38;Somatic Mutation;synergism;Testing;Therapeutic;Topoisomerase I inhibition;Topoisomerase-I Inhibitor;Topotecan;Toxic effect;treatment response;tumor;Type I DNA Topoisomerases;Woman

PROJECT_TITLE: Project 2: Next Generation TOP1 Inhibition for the Treatment of Ovarian Cancer


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Colorectal Cancer;Data Science;Digestive Diseases;Genetics;Human Genome;Microbiome

PI_NAMEs: LIU, QI  (contact)

PROJECT_TERMS: adenoma;Animals;Area;Bioinformatics;Biological Sciences;Biometry;Cancer Biology;Cells;Cellular biology;Clinical Research;Collaborations;Colon;Communication;Data Analyses;data integration;Dedications;Ensure;epigenomics;Epithelium;exome sequencing;experience;Experimental Designs;Funding;Genomics;Goals;Grant;Human;Human Resources;Immune;Individual;Institution;Joints;Laboratories;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of gastrointestinal tract;Malignant Neoplasms;meetings;member;Methods;microbiota;Modeling;multidimensional data;Multiomic Data;multiple omics;novel;premalignant;programs;Proteomics;Publications;Qi;Quality Control;Recording of previous events;Research Design;Research Project Grants;Science;Services;Shapes;Signal Transduction;skills;Systems Biology;Technology;transcriptome sequencing;transcriptomics;Trust;Work

PROJECT_TITLE: Quantitative Bioscience Core


ORG_CITY: CARLSBAD

ORG_NAME: CROSSLIFE TECHNOLOGIES, INC.

PHR: A Rapid HIV RNA Detection without Sample Preparation CrossLife Technologies Inc. Narrative We propose to develop a rapid, sensitive, specific, simple, and cost-effective diagnostic – “TARApen” – by integrating innovations in biomolecular recognition (TARA) and microfluidic design that address the key limitations of current home-test kits. The resulting TARApen test will automate all steps of molecular analysis and amplification for detection of HIV RNAs in blood finger-stick without sample preparation.

PI_NAMEs: CHO, HYUNDAE  (contact)

PROGRAM_OFFICER_NAME: MAJJI, SAI PRASANNA

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Acute;acute infection;Address;Adopted;Africa;amplification detection;Antibodies;Antibody Response;antiretroviral therapy;Asia;Automation;Awareness;Biological Assay;Blood;Blood specimen;Brazil;Buffers;Chemicals;Chemistry;Clinical;co-infection;Collaborations;Communicable Diseases;Complementary DNA;cost;cost effective;Cytolysis;design;Detection;detection assay;Developed Countries;Devices;Diagnosis;Diagnostic;Diagnostic Equipment;Diagnostic Reagent Kits;diagnostic strategy;diagnostic technologies;digital;drug resistance development;Dryness;Early Diagnosis;Early treatment;emerging virus;Engineering;Epidemic;Equipment;Family health status;Feedback;Fingers;Fostering;Generations;global health;Goals;Health;Healthcare;high risk population;HIV;HIV Infections;HIV-1;Home;home test;Human immunodeficiency virus test;Immunoassay;improved;Individual;Infection;Infection Control;innovation;instrument;Intervention;isothermal amplification;Knowledge;Laboratories;Latin America;Letters;Malaysia;Marketing;Medical;Microfluidic Microchips;Microfluidics;Molecular;Molecular Analysis;Monitor;Morbidity - disease rate;mortality;Mothers;multidisciplinary;multiplex detection;nasopharyngeal swab;Newborn Infant;Newly Diagnosed;nucleic acid detection;nucleic acid purification;Nucleic Acids;Outcome Measure;Patients;Performance;Persons;Pharmacy facility;Phase;Plasma;point of care;Preparation;prevent;Prevention;Privacy;Process;prospective;prospective test;Quantitative Reverse Transcriptase PCR;rapid test;Reaction;Reagent;Resistance;Resource-limited setting;Resources;Risk;Risk Reduction Behavior;RNA;RNA purification;Saliva;sample archive;Sampling;screening;self testing;seroconversion;Serum;social stigma;Specificity;System;Technology;technology development;technology platform;technology validation;Temperature;Testing;Time;transmission process;Urine;Validation;Viral load measurement;Viral Load result;viral rebound;Viremia


PI_NAMEs: SINGH, BHUMINDER  (contact)

PROJECT_TERMS: adenoma;Apical;Autologous;Biological Sciences;Cancer Center;Cell Line;Cell Separation;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Colon;colon cancer patients;Colorectal Cancer;Communication;cytotoxic CD8 T cells;Cytotoxic T-Lymphocytes;DNA;Ensure;Epithelial Cells;Epithelium;Equipment;Escherichia coli;exome sequencing;experience;experimental study;Feasibility Studies;Funding;Future Generations;Generations;Genes;Genetic;Germ Lines;Goals;Grant;Human;Human Resources;Immune;Immunologist;Individual;Infrastructure;Institution;interest;knockout gene;Lesion;matrigel;medical schools;microbial;microbiota;Modeling;Monitor;monolayer;Mucous Membrane;neutrophil;Organoids;overexpression;Participant;Patients;pharmacologic;Pilot Projects;Pre-Clinical Model;premalignant;protein expression;repository;Research Personnel;Resources;Services;Shapes;Specimen;System;Technical Expertise;Universities;Villous Adenoma;Work;Xenograft procedure

PROJECT_TITLE: Human Pre-Cancer Models


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

PHR: NARRATIVE – PROJECT 3 Poly(ADP-ribose) polymerase (PARP) inhibitors have recently been FDA approved as maintenance therapy to extend progression-free survival in ovarian cancer. Here we study the effect of combining PARP inhibitors with an FDA-approved drug (the ALK inhibitor ceritinib) that is not currently used to treat high-grade serous ovarian cancer (HGSOC). Based on a novel mechanism of action we have discovered and the synergistic activity of the ceritinib + PARP inhibitor combination, we propose additional preclinical studies to better understand the mechanism by which this combination kills ovarian cancer cells in tissue culture and in ovarian cancer patient- derived xenografts in vivo. In addition, we propose to perform a phase 1b clinical trial of ceritinib in combination with the PARP inhibitor olaparib with an expansion phase in HGSOC to assay toxicity, assess potential activity, and explore biomarkers of response identified in the mechanistic and PDX studies.

PI_NAMEs: KARNITZ, LARRY M (contact)

PROJECT_TERMS: 3-Dimensional;Address;Affect;Animal Model;Antitumor Response;base;Base Excision Repairs;Bioinformatics;Biological Assay;Biological Markers;biomarker identification;Biometry;brca gene;BRCA mutations;cancer cell;Cancer cell line;Cancer Patient;cancer therapy;Cell Line;Clinic;Clinical;Code;cohort;Cohort Studies;Correlative Study;CRISPR screen;cytotoxic;cytotoxicity;Data;Defect;design;Development;Disease;Disease Resistance;DNA Damage;DNA Repair;DNA Repair Gene;DNA Repair Pathway;Dose;Drug Kinetics;Excision;Excision Repair;FDA approved;Future;Gene Mutation;Genes;Genotype;Goals;homologous recombination;Immune system;Immunocompetent;improved outcome;In Vitro;in vivo;in vivo Model;Individual;inhibitor;insight;kinase inhibitor;Libraries;loss of function;Maintenance Therapy;Malignant neoplasm of ovary;Mitochondria;Modeling;Mus;Mutation;Non-Small-Cell Lung Carcinoma;novel;novel therapeutics;Oxidative Phosphorylation;partial response;Pathway interactions;patient derived xenograft model;patient registry;Patient Selection;Patients;Pharmaceutical Preparations;Phase;Phase Ib Clinical Trial;Phase Ib Trial;phase II trial;Phenotype;Phosphotransferases;Plasma;Platinum;Poly(ADP-ribose) Polymerase Inhibitor;Poly(ADP-ribose) Polymerases;potential biomarker;preclinical study;predicting response;prevent;Process;Production;Progression-Free Survivals;Protein Tyrosine Kinase;Proteins;Reactive Oxygen Species;Recurrence;Relapse;repaired;Reporting;Resistance;Respiration;response;response biomarker;Safety;safety assessment;Sampling;Serous;small molecule;synergism;Therapeutic;Time;tissue culture;Toxic effect;tumor;women's treatment;XRCC1 gene

PROJECT_TITLE: Project 3:  Repurposing Ceritinib for Ovarian Cancer Therapy


ORG_CITY: BOSTON

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

PHR: Not Required

PI_NAMEs: POGODA, TERRI K. (contact)

PROJECT_TERMS: disability payment;Post-Traumatic Stress Disorders;Services;Veterans;Work

PROJECT_TITLE: Does Protecting Service-Connected Disability Income Motivate Return to Work in Veterans with TBI and PTSD?

STUDY_SECTION_NAME: Innovation Initiative 2[HSN2]


ORG_NAME: VA  MEDICAL CENTER

PHR: Background: Tinnitus and hearing loss are among the most common service-connected disabilities with Veterans being at particular risk for severe hearing loss. Comprehensive hearing health services are available within the VA to qualifying veterans. The delivery of optimal hearing healthcare mandates tailored treatments are offered based on degree of hearing loss and patient preferences. These options are defined in practice guidelines including the VA since 2004. Significance/Impact: Despite the prevalence of hearing loss among Veterans, there are few projects studying the management of those with severe hearing loss. Ensuring appropriate treatments for those most severely affected represents an important access to care issue with implications for patients’ communication, quality of life and overall health. This also facilitates patient communication in health care settings as being able to hear is a cornerstone of participation in shared-decision making. Innovation: The VA is the ideal setting to study management of severe hearing loss as this is a prevalent condition among veterans, interested patients are offered comprehensive treatments for hearing loss and longitudinal audiometric data are available to allow identification of factors associated with receipt of particular treatment strategies. Stakeholder engagement including interviews with affected Veterans and providers are incorporated in the study design. Specific Aims: 1. Define the prevalence, modes of treatment and time to treatment of Veterans with severe  hearing loss using the Audiometric Repository, a national database of audiograms and a  registry of assistive listening devices, hearing aids and cochlear implants within the VA,  between 2005-2017. 2. Identify which factors are associated with different treatment approaches for Veterans with  severe hearing loss using the Audiometric Repository linked to administrative data from the  electronic medical record during years 2005-2017. 3. Identify facilitators and barriers for distinct management of severe hearing loss among hearing  aid users (including referral for cochlear implants) through semi-structured interviews with  current VHA providers (audiologists, otolaryngologists and primary care providers) and  affected Veterans. Methodology: A mixed methods study using a sequential explanatory design will be employed. Data from the Audiometric Repository will be linked to administrative data from the electronic health record to understand management of Veterans with severe hearing loss. Interviews will be conducted with various stakeholders including Veterans and providers to identify barriers and facilitators to particular treatment modalities. Next Steps/Implementation: Results from this pilot will provide new information on barriers and facilitators of management of severe hearing loss. In addition to a planned manuscript describing our findings, we will develop educational materials for providers on CI indications and criteria for referral. We will also develop an educational brochure for Veterans and families to address potential attitudinal/knowledge barriers. These materials will form the basis for a Merit application to study trajectories of hearing loss and to develop and test an implementation approach to achieve best practices in the treatment of severe hearing loss.

PI_NAMEs: FRIEDMANN, DAVID R (contact)

PROJECT_TERMS: Acoustics;Address;Adherence;Affect;Age;age related;Age Years;American;Attitude;Audiology;Bilateral;Caring;Clinical Management;clinical practice;Cochlear implant procedure;Cochlear Implants;Communication;comorbidity;Computerized Medical Record;connected health;cooperative study;Counseling;Data;Databases;design;Diabetes Mellitus;disability;Disabling;Education;Educational Materials;Elderly;electronic data;electronic health data;Electronic Health Record;Eligibility Determination;Ensure;Evidence based intervention;Family;functional decline;Geographic Locations;Goals;Guidelines;Health;health care settings;health service use;Health Services;Health Services Accessibility;Healthcare;Hearing;Hearing Aids;hearing impairment;hearing loss treatment;Hearing Tests;Impaired cognition;Improve Access;improved;Individual;individualized medicine;inhibitor;innovation;interest;Intervention;Interview;Knowledge;Link;Literature;Manuscripts;Medical;Mental Depression;Methodology;Methods;military service;Modality;Neurocognitive Deficit;noise exposure;Otolaryngologist;Outcome;Outpatients;Pamphlets;Patient Preferences;patient subsets;Patients;Personal Satisfaction;Practice Guidelines;Prevalence;prevent;primary care provider;Procedures;Process;programs;prospective;Prosthesis;Provider;provider factors;Psyche structure;Qualifying;Quality of Care;Quality of life;Recommendation;Registries;Rehabilitation therapy;repository;Research Design;Research Methodology;research study;Risk;Schedule;Services;shared decision making;Social isolation;sociodemographic variables;sound;Specialist;Structure;System;systematic review;Testing;Time;Tinnitus;treatment strategy;United States Agency for Healthcare Research and Quality;Update;verbal;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Resubmssion: Management of Severe Hearing Loss in the Veterans Health Administration

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Immunotherapy;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

PHR: NARRATIVE – PROJECT 4 Novel treatment options for women with recurrent ovarian cancer are desperately needed. The overarching goal of Project 4 is to develop and test genetically engineered natural killer (NK) cells to be more effective at identifying and killing ovarian cancer cells. Project 4 will leverage advanced gene editing techniques to remove an intracellular signaling protein that dampens NK activation (CISH gene) and insert a chimeric antigen receptor (CAR) that was developed specifically for NK cells, targeting the prevalent epithelial ovarian cancer (EOC) tumor antigen mesothelin (MSLN). Our central hypothesis is that gene editing can be used to overcome signaling inhibition and improve NK targeting, persistence and function, thereby resulting in improved therapeutic outcomes for women with recurrent EOC.

PI_NAMEs: MORIARITY, BRANDEN S (contact)

PROJECT_TERMS: Activated Natural Killer Cell;Address;Adult;Affect;Allogenic;Animal Model;Antigen Targeting;Antigens;arm;Ascites;B lymphoid malignancy;Binding;Biometry;Blood;cancer cell;CAR T cell therapy;CD19 gene;Cell Line;Cell Survival;Cell Therapy;Cells;Cellular biology;Characteristics;chimeric antigen receptor;chimeric antigen receptor natural killer cells;Chromosomal Instability;Chronic;CISH gene;Clinic;Clinical;Clinical Trials;Clinical Trials Design;Clustered Regularly Interspaced Short Palindromic Repeats;Correlative Study;CRISPR/Cas technology;cytokine;cytokine release syndrome;Cytokine Signaling;Data;design;Development;Diagnosis;Disadvantaged;Dose;Electroporation;engineered NK cell;Engineering;Epithelial ovarian cancer;Excision;exhaustion;Future;gene-editing approach;Genes;Genetic;Genetic Engineering;Goals;graft vs host disease;Guide RNA;Human;Immune;immune checkpoint blockade;Immunotherapy;improved;improved outcome;In Vitro;in vivo;Interleukin-15;interleukin-21;Intracellular Signaling Proteins;K-562;Knock-in;Knock-out;Knockout Mice;Learning;Ligands;Malignant neoplasm of ovary;Malignant Neoplasms;Maximum Tolerated Dose;Measures;Membrane;mesothelin;Methods;Modification;molecular targeted therapies;Mutate;Mutation;Natural Killer Cell Immunotherapy;Natural Killer Cells;Neoplasm Metastasis;NK Cell Activation;NK cell therapy;novel;novel therapeutics;PARP inhibition;patient derived xenograft model;Patients;peripheral blood;Peritoneal;phase 1 designs;Phase I Clinical Trials;Phase I/II Trial;Physiological;Preclinical Testing;Process;programs;Proliferating;Proteins;Protocols documentation;Receptor Cell;Receptor Gene;Recombinant adeno-associated virus (rAAV);Recurrence;Refractory;Research;Resistance;resistance mechanism;Resources;response;RNA;secondary outcome;side effect;Signal Pathway;Signal Transduction;Site;site-specific integration;Solid Neoplasm;Specificity;success;Surface;Survival Rate;T cell therapy;T-Lymphocyte;Techniques;Testing;therapy outcome;Toxic effect;Tumor Antigens;tumor microenvironment;tumor progression;Vascular Endothelial Growth Factors;Viral;Woman;women's diagnosis;women's outcomes;Work

PROJECT_TITLE: Project 4 Treatment of Advanced Ovarian Cancer Using Gene-Edited NK CAR Cells