NIH_SPENDING_CATS: Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Cancer Genomics;Colorectal Cancer;Data Science;Digestive Diseases;Genetics;Human Genome

PI_NAMEs: ZHAO, SIMING  (contact)

PROJECT_TERMS: Address;Affect;Alleles;Applications Grants;Area;Autopsy;Biological;Biology;career;causal variant;Cell Line;cell type;Cells;Centers of Research Excellence;Chromatin;cohort;Collaborations;Colon;Colonic Diseases;Colorectal Cancer;Complex;Computing Methodologies;CRISPR interference;cytokine;Data;Data Analyses;Data Collection;data resource;Data Science Core;Data Set;data to knowledge;Development;Disease;Educational process of instructing;epigenetic marker;Epigenetic Process;Faculty;functional genomics;Funding;Future;Gene Expression;Generations;Genetic;Genetic Diseases;Genetic study;genetic variant;genome wide association study;Genomic approach;genomic data;Genotype;Goals;Heritability;Human;human disease;Inflammatory Bowel Diseases;inflammatory milieu;insight;Laboratories;Learning;machine learning method;Maps;Measures;Mentors;method development;Methodology;Multiomic Data;multiple omics;Organism;Organoids;Pathogenesis;Play;Quantitative Trait Loci;Recording of previous events;Research;Research Design;Research Project Grants;Resources;Role;Sample Size;Sampling;senior faculty;single cell ATAC-seq;single cell genomics;single-cell RNA sequencing;Techniques;Tissues;trait;transcriptome sequencing;translational genomics;Variant;Work

PROJECT_TITLE: Zhao - Proj 2


ADMINISTERING_IC: GM

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Clinical Research;Genetics;Human Genome;Microbiome

ORG_CITY: HANOVER

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PI_NAMEs: SONG, LI  (contact)

PROJECT_TERMS: Antigens;Applications Grants;B-Cell Antigen Receptor;Bacteria;Bacterial Infections;base;behavioral study;Binding;Bioinformatics;Biological;Biology;career;career development;Cells;Centers of Research Excellence;Classification;Communities;Computer software;Computing Methodologies;Data;Data Set;Databases;design;Detection;Disease;Ensure;Evaluation;Exhibits;experimental study;Foundations;Funding;Future;Goals;Grant;Head;Health;human disease;Immune;Immune response;Immune system;Immunologic Receptors;immunoreaction;improved;indexing;Individual;Infrastructure;insight;interdisciplinary collaboration;Length;Memory;Mentors;Metagenomics;method development;Methods;Microbe;microbiome;Mining;nanopore;neoantigens;novel;open source;Organism;Pattern;Persons;Play;Procedures;Process;Proliferating;receptor;receptor binding;reconstruction;Recording of previous events;Research;Research Personnel;Resources;Role;Running;Sampling;sequencing platform;single cell genomics;skills;Specificity;success;Suggestion;T cell receptor repertoire sequencing;T-Cell Antigen Receptor Specificity;T-Cell Receptor;T-cell receptor repertoire;T-Cell Receptor Therapy;T-Lymphocyte;Techniques;tool;transcriptome sequencing;treatment strategy;tumor;user-friendly;Virus;Virus Diseases;Work

PROJECT_TITLE: Song - Proj 3

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 RCB-3 (C2)]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Cancer Genomics;Clinical Research;Data Science;Epilepsy;Genetics;Human Genome;Neurodegenerative;Neurosciences;Rare Diseases

PI_NAMEs: HONG, JENNIFER  (contact)

PROJECT_TERMS: Address;Affect;Automobile Driving;biobank;Biological;biological specimen archives;Biology;Brain;Brain Neoplasms;Brain Pathology;brevican;career;cell cortex;cell type;Cells;Centers of Research Excellence;Clinical;Clinical Data;clinical translation;clinically relevant;Collaborations;Complex;complex data;computational pipelines;Computational Technique;Computer Analysis;Data;Data Science Core;Data Set;Databases;Dedications;Development;digital;Drug toxicity;effective therapy;Enrollment;Environment;Epilepsy;epileptiform;Equipment;Evaluation;experience;experimental study;Extracellular Matrix;Faculty;Funding;Gene Expression;Genetic Transcription;genomic data;Glioma;Goals;Grant;Growth;high dimensionality;Histologic;Histological Techniques;Human;human tissue;Immune;improved;Individual;Infrastructure;inhibitor;innovation;interest;Interneurons;Invaded;Investigation;Knowledge;Link;Long term disability;Machine Learning;Maps;Matrix Metalloproteinases;Medical;Mentors;Mentorship;Methods;Mission;Molecular;Molecular Epidemiology;Molecular Structure;Morbidity - disease rate;Morphology;mouse model;multidimensional data;Nervous System Disorder;Neurologic;Neurologic Symptoms;Neuronal Dysfunction;neuronal tumor;Neurons;Neurosurgeon;neurosurgery;new therapeutic target;novel;novel therapeutic intervention;Organism;Oxidative Stress;Pathogenesis;Pathway interactions;Patients;Peptide Hydrolases;Pharmaceutical Preparations;preservation;Proliferating;protein expression;protein profiling;Proteins;Quality of life;Recording of previous events;Recurrence;Refractory;Regulation;Research;Research Personnel;Research Project Grants;Resources;Risk Factors;RNA;Role;Scientist;Seizures;Signaling Molecule;single cell genomics;single nucleus RNA-sequencing;single-cell RNA sequencing;skills;Source;Specimen;Stromal Neoplasm;Structure;successful intervention;Synapses;System;Technology;Testing;therapeutic target;Time;Tissues;tool;Training;Transcript;transcriptomics;transfer learning;Translational Research;transmission process;treatment strategy;tumor;Tumor Markers;tumor microenvironment;tumor progression;Tumor Promotion;Tumor Subtype;United States National Institutes of Health

PROJECT_TITLE: Hong Proj-4


ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Our work focuses on how signaling networks generate complex cellular behaviors such as cell movement and immune cell activation. The ability to control cell migration would be a valuable tool for combating atherosclerosis, inflammation, metastasis, and other pathological processes that occur upon the disruption of cellular guidance mechanisms. The proposed supplemental activities are within the scope of the parent grant, no changes.

PI_NAMEs: WEINER, ORION D (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Acceleration;Address;antigen binding;Antigens;Atherosclerosis;Behavior;Biological;Biosensor;Buffers;cell behavior;Cell Line;Cell membrane;cell motility;Cell Polarity;Cell Shape;Cell surface;cell type;Cells;Cellular biology;Collaborations;Communication;Communities;Compensation;Complex;Computer Vision Systems;Decision Making;Enhancers;experience;experimental study;Feedback;Gene Activation;Generations;Geometry;Goals;immune activation;Immune system;improved;Individual;Inflammation;interest;Investigation;Lead;lens;Light;Logic;Lymphocyte;Membrane;Mentors;Microscopy;Molecular;Morphogenesis;Morphology;Mouse Embryonic Stem Cells;Movement;Neoplasm Metastasis;neutrophil;optogenetics;Oral;Organism;Paper;parent grant;Parents;Pathologic Processes;Pattern;Peptides;PIK3CG gene;Positioning Attribute;Postdoctoral Fellow;Process;promoter;Property;Publications;Research;Research Project Grants;Resolution;Role;Science;Sea;Shapes;Signal Transduction;skills;Specific qualifier value;Structure;success;System;T-Cell Activation;T-Lymphocyte;Techniques;Testing;tool;transcription factor;Transcriptional Activation;transmission process;Visualization;Work;Writing;X-Ray Tomography

PROJECT_TITLE: Cellular Decision Making

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: LA JOLLA

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Komor – Project Narrative – “Development and Application of New Genome Editing Tools for the Functional Investigation of Genetic Variants of Uncertain Significance” Our inability to interpret the clinical consequences of genetic variants discovered by sequencing remains a critical obstacle to the progress of precision medicine: out of the 4.6 million missense variants identified in the Genome Aggregation Database, over half are admitted to be variants of uncertain significance (VUS). New methods capable of interpreting VUS would not only enhance the efficacy of current therapies by better informing patient selection strategies, but also accelerate the development of new approaches to combat diseases with a genetic component. Here we propose the development of new genome editing tools and platforms that will allow researchers to functionally interrogate thousands of VUS individually, in combination, and in aggregate, to produce clinically-relevant information on how genetic variations cause human disease.

PI_NAMEs: KOMOR, ALEXIS C. (contact)

PROGRAM_OFFICER_NAME: KRASNEWICH, DONNA M

PROJECT_TERMS: Acceleration;Adenine;Admission activity;aggregation database;Area;base editing;base editor;Base Pairing;Bioinformatics;Cells;Chemicals;Chemistry;Clinical;clinically relevant;combat;Communities;CRISPR/Cas technology;Cytosine;Deamination;design;Development;Directed Molecular Evolution;Disease;DNA Double Strand Break;Enzymes;Gene Mutation;Genetic;Genetic Diseases;genetic variant;Genetic Variation;Genome;genome editing;Genomic DNA;human disease;Human Genetics;Individual;interest;Investigation;Methodology;Methods;Modification;novel strategies;nucleobase;Pathogenicity;Patient Selection;Point Mutation;precision medicine;programs;Research;Research Personnel;Single-Stranded DNA;Time;tool;Variant;variant of unknown significance;Work


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Posttraumatic stress disorder (PTSD) disrupts romantic relationships and other aspects of psychosocial functioning, which can worsen Veterans' PTSD symptomatology and interfere with their long-term recovery. The proposed four-year study aims to reduce PTSD symptoms and improve relationship functioning among Veterans with PTSD. Dr. Morland (PI) and Dr. Sippel (PI) propose to examine the effects of couples' therapy for PTSD augmented with intranasal oxytocin, a neurohormone that affects mechanisms of trauma recovery and social behavior, on Veterans' PTSD and psychosocial functioning, and both Veterans' and partners' relationship satisfaction. The study will also explore the impact of intranasal oxytocin on potential mechanisms of action. Brief Cognitive-Behavioral Conjoint Therapy will be combined with intranasal oxytocin or placebo condition to determine the efficacy of the oxytocin augmentation, thereby advancing knowledge of strategies for improving Veterans' psychosocial functioning by improving their personal relationships.

PI_NAMEs: MORLAND, LESLIE A. (contact);SIPPEL, LAUREN

PROJECT_TERMS: Address;Affect;Aftercare;Anger;Behavioral;Birth;care episode;Caring;Child Rearing;Clinical;Cognitive;Communication;community engagement;Conflict (Psychology);Couples;Couples Therapy;Data;design;Diagnosis;Distress;Dose;efficacy evaluation;Elements;Eligibility Determination;Empathy;Employment;Evaluation;evidence base;Evidence based treatment;Extinction;Family;flexibility;follow-up;Friendships;Fright;Functional disorder;functional outcomes;Future;Goals;Healthcare;Healthcare Systems;Homelessness;improved;Individual;innovation;International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10);International Unit;Intervention;Investigation;Knowledge;knowledge translation;Lactation;long term recovery;loved ones;Manuals;manufacture;Mediator;Mental Health;Mental Health Services;Methods;military veteran;Neurohormones;Neuropeptides;novel;Outcome;Oxytocin;Partner in relationship;pharmacologic;Placebo Control;Placebos;Post-Traumatic Stress Disorders;Process;psychosocial;Psychotherapy;Randomized;randomized, clinical trials;Recovery;recruit;Regulation;Rehabilitation therapy;Reporting;Risk;Role;Sampling;satisfaction;Self Administration;Services;Severities;skills;social;Social Behavior;Stress;stressor;substance misuse;Substance Use Disorder;suicidal risk;Suicide;symptomatology;Symptoms;telehealth;Therapeutic;therapy design;Translations;Trauma;Trauma recovery;Treatment outcome;Trust;United States Department of Veterans Affairs;Veterans;Violence;Withdrawal;Work

PROJECT_TITLE: A Randomized Clinical Trial Examining Intranasal Oxytocin Augmentation of Brief Couples Therapy for Veterans with PTSD

STUDY_SECTION_NAME: Behavioral Health & Social Reintegration[RRD4]


ADMINISTERING_IC: DP

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL CENTER FOR CHRONIC DISEASE PREVENTION AND HEALTH PROMOTION

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Reliable, timely surveillance data on the prevalence and incidence of diabetes among youth in the U.S. is needed to identify current and future healthcare and public health priorities. Ongoing estimates are critical to determine the needs and monitor the effects of treatment to reduce complications and design effective prevention activities. It is of critical importance to identify groups or populations that might have increased burden or special health care needs related to diabetes.

PI_NAMEs: CRUME, TESSA L (contact);DABELEA, DANA

PROJECT_TITLE: DP20-001 Surveillance of Diabetes in Children and Adolescents between 0-17 Years of Age (DiCAYA) - Component A


ADMINISTERING_IC: OH

ED_INST_TYPE: OVERALL MEDICAL

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_CITY: PORTLAND

ORG_DEPT: NEUROSCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The Oregon Healthy Workforce Center provides outreach and education to OSHA Region 10 (Oregon, Washington, Alaska, and Idaho) and has broader national and international research dissemination impacts. Our research projects contribute to our theme of TWH intervention effectiveness and translation to advance safe and healthy work design. These projects all employ organizational and individual change strategies linked to outreach, education and dissemination, and translation strategies to produce health, safety, and well-being changes that can be scaled and shared broadly.

PI_NAMEs: HAMMER, LESLIE  (contact);OLSON, RYAN

PROJECT_TITLE: Oregon Healthy Workforce Center


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: ATLANTA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative: Results from recent TCGA and pathological studies imply the oncogenic role for B7- H4 in breast tumor evasion and progression, although the underlying molecular mechanisms by which dysregulation of B7-H4 contributes to breast tumor evasion, progression and metastasis remain unknown. This proposal will determine the impact of interplay between glycosylation and ubiquitylation of B7-H4 in breast carcinogenesis and anti-breast cancer therapy, and further seek for new therapeutic strategy to enhance chemotherapy agent (such as doxorubicin)-induced immunogenic cell death through blockade of B7-H4 blockade for anti-breast cancer treatment, especially for triple negative type breast cancers. Completion of this project will uncover the tumor immune suppression role of B7-H4 in breast carcinogenesis, and could provide a new strategy for breast cancer therapy by targeting B7-H4 glycosylation.

PI_NAMEs: WAN, YONG  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Breast Cancer therapy;Breast Cancer Treatment;Breast Carcinogenesis;cancer type;carcinogenesis;CD8-Positive T-Lymphocytes;CD8B1 gene;Cellular Stress;Chemosensitization;chemotherapy;clinical efficacy;clinically relevant;Complex;Data;Dendritic Cells;Doxorubicin;endoplasmic reticulum stress;Enzymes;glycosylation;glycosyltransferase;Goals;Heat-Shock Proteins 70;Heat-Shock Proteins 90;immune checkpoint;Immune checkpoint inhibitor;immunogenic cell death;Immunosuppression;Immunotherapy;in vivo;inhibitor;Interferon Type II;Lead;Malignant Breast Neoplasm;Mammary Neoplasms;Mediating;Modeling;Molecular;mouse model;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutic intervention;Oncogenic;Pathologic;Pattern;Phagocytosis;Pharmaceutical Preparations;pharmacologic;Physiological;Post-Translational Protein Processing;pre-clinical;Prognosis;protein complex;Protein Glycosylation;Proteins;recruit;response;Role;Signal Transduction;T cell response;T-Lymphocyte;targeted cancer therapy;Testing;The Cancer Genome Atlas;Therapeutic;triple-negative invasive breast carcinoma;tumor;tumor eradication;Tumor Escape;tumor progression;Tumor Promotion;ubiquitin-protein ligase;Ubiquitination;VTCN1 gene

PROJECT_TITLE: Targeting posttranslational modifications of B7-H4 in carcinogenesis and therapy

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative We propose a Louisiana Natural Experiment Center (LNEC) to examine the impact of Zero-Dollar Copayment (ZDC) for select medications as part of disease management services to improve medication adherence for patients with type 2 diabetes mellitus in Louisiana where the prevalence of diabetes and mortality from cardiovascular disease are among the highest across all the regions of the United States. The intended outcome of the ZDC program to address cost-related non-adherence as part of the social determinants of health (SDH) is to inform, engage, and empower patients to achieve better health outcomes. The proposed LNEC will generate urgently needed data on effective, practical, and sustainable population-targeted strategies aimed at addressing SDH, eliminating health disparities, and reducing diabetes-related disease burden in the United States.

PI_NAMEs: SHI, LIZHENG  (contact)

PROJECT_TITLE: DP20-002, Louisiana Experiment to Address Diabetes: Zero-Dollar Copayment (LEAD-ZDC) for Improving Disease Management


ORG_CITY: HYATTSVILLE

ORG_NAME: MEDSTAR HEALTH RESEARCH INSTITUTE

ORG_STATE: MD

PHR: Project Narrative We aim to improve quality of life and well-being among breast and prostate cancer survivors by simultaneously targeting anti-racism training in clinical settings and using universal social determinants of health screening and referral to address such needs. Community health workers utilizing health information exchange in DC will be central to improving community-clinical linkages and decreasing social isolation among cancer survivors. Our long-term goal is to decrease cancer outcome disparities in the Washington DC region.

PI_NAMEs: AREM, HANNAH  (contact);PRATT-CHAPMAN, MANDI L.

PROJECT_TITLE: DP21-003 Scaling Social Determinants of Health Screening, Social Support and Anti-Racism Training to Reduce Inequities in Minority Cancer Survivor Health and Wellbeing in Washington, DC


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: The Center for Health, Work & Environment will have high public health impact by meeting Region 8 and national needs for healthy and safe worksites and workers through its program of research, r2p, education/training, partnerships and other dissemination activities. It will advance scientific knowledge by establishing new, innovative worksite programs to benefit both workers and employers, test relevant theoretical models, and emphasize helping those working in small enterprises, and in other high-risk industries, including education and agriculture, among other sectors with high need.

PI_NAMEs: NEWMAN, LEE S (contact)

PROJECT_TITLE: Center for Health, Work and Environment


ORG_CITY: BOSTON

ORG_DEPT: SOCIAL SCIENCES

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

ORG_STATE: MA

PHR: HARVARD CENTER FOR WORK, HEALTH AND WELL-BEING: OVERALL PROJECT NARRATIVE The Harvard T.H. Chan School of Public Health Center for Work, Health, and Well-being aims to improve the health, safety, and well-being of working populations by conducting research to identify working conditions that influence worker health outcomes; testing intervention methods to improve these outcomes; and translating this research into best practice and policies. The Center additionally seeks to understand and characterize disparities in workers’ exposures and health outcomes in relation to socioeconomic position, race/ethnicity, and age, in order to guide recommendations to address those disparities. The Center will respond to the need for an evidence base that will inform development and implementation of effective workplace and public policies in promoting and protecting worker safety, health, and well-being.

PI_NAMEs: SORENSEN, GLORIAN C (contact)

PROJECT_TITLE: The Harvard TH Chan School of Public Health Center for Work, Health and Wellbeing


ORG_CITY: SALT LAKE CITY

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: NARRATIVE (OVERALL CENTER) The Utah Center for Promotion of Work Equity Research (U-POWER) envisions work and workplaces that are safe, healthy, and equitable, and has the mission of U-POWER is to create a sustainable community of practice that changes the conditions of work and advances Total Worker Health® (TWH) through research and outreach. The integrating theme of U-POWER is the role of power in defining work conditions that create and sustain inequity and ill health among workers. U-POWER will facilitate a community of practice that shares the concern of changing the conditions of work and advancing TWH and advance TWH through innovative research and outreach, guided by the translational research process and community engagement.

PI_NAMEs: AHONEN, EMILY QUINN (contact)

PROJECT_TITLE: Utah Center for Promotion of Work Equity (U-POWER)


ORG_CITY: NEW YORK

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative  New intervention technology to reduce the transmission of airborne diseases is vital to improve public health, and is especially needed within healthcare environments where workers are substantially more at risk of becoming ill. Irradiation with far-UVC wavelengths, specifically from 200-230 nm, is a promising solution which we have previously shown to be effective at inactivating airborne viruses and, unlike conventional UV irradiation, has shown promise as being safe for human exposure. This work will test the biological effects of far-UVC radiation upon the eyes and skin of mice; these results are necessary to evaluate health hazards from exposure to these wavelengths and are critical for the adoption of this new technology.

PI_NAMEs: WELCH, DAVID  (contact)

PROJECT_TITLE: Testing health hazards from implementation of far-UVC irradiation as an intervention technology to reduce airborne disease transmission

STUDY_SECTION: SOH

STUDY_SECTION_NAME: Safety and Occupational Health Study Section[SOH]


ORG_CITY: DANVILLE

ORG_NAME: GEISINGER CLINIC

ORG_STATE: PA

PHR: Narrative Currently there are 4.6 million young adults (18 to 44 years of age) with diabetes in the US and the incidence and prevalence estimates in this age group have been increasing. However, due to limitations of traditional surveillance strategies, it remains unknown whether these increases are in type 1 or type 2 diabetes. The proposed research will coordinate, develop, implement, and validate electronic-record based surveillance of diabetes in young adults, by subtype, to inform type-specific public health responses, assess disease burden, and identify priorities for type-specific health services.

PI_NAMEs: HIRSCH, ANNEMARIE GREGORY (contact)

PROJECT_TITLE: DP20-001 Electronic Health Record-based Surveillance of Diabetes by Type in Young Adults in Pennsylvania


PHR: Project Narrative – California Labor Laboratory The goal of our Total Worker Health Center, the California Labor Laboratory, is to describe, understand the causes of, and prevent or mitigate the health impacts of emergent working conditions, with a special emphasis on those vulnerable to those conditions, including members of racial and ethnic minorities; women; immigrants; low wage workers; persons with disabilities; and younger and older workers, especially those with existing chronic diseases. California not only has the largest population of any state, at just under 40 million, but it is among the most diverse in its racial and ethnic composition and in the mix of its industries and it has also been a trend-setter in work organization, with large proportion of the workforce not having a full-time, full-year job at a single workplace and not being directly hired by the firm for which the work is done. The proposed Center has a comprehensive research program of five projects focused on the health impacts of changes in working conditions and a comprehensive outreach program consisting of interdisciplinary training for health professionals and the public, development of a cadre of researchers devoted to understanding the health impacts of emerging work through a pilot grants program, consulting to groups of workers and firms on best practices for healthy employment, and development of a public policy agenda and engagement with policymakers to address the adverse impacts of working conditions through law and regulation.

PI_NAMEs: YELIN, EDWARD H (contact)

PROJECT_TITLE: California Labor Laboratory (CALL)


ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE The UIC Center for Healthy Work’s mission is to remove barriers that impact the health of low wage workers in the increasingly contingent workforce. We aim to identify and promote employment programs, practices, and policies that will improve worker and community health locally, across the state, and throughout the nation. Our vision is a future of work that promotes inclusive and equitable opportunities for healthy work and healthy work is recognized as a social and structural determinant of health and a human right, a pathway to advancing systemic change and racial justice, and a significant contributor to workforce well-being.

PI_NAMEs: ALMBERG, KIRSTEN STAGGS (contact)

PROJECT_TITLE: UIC Center for Healthy Work


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

FUNDING_MECHANISM: OTHERS

ORG_CITY: Columbus

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: 8. Project Narrative See Program Plan under PHS398 Research Training Program Plan

PI_NAMEs: SOMMERICH, CAROLYN M (contact)

PROJECT_TITLE: Occupational Safety and Health Training Grant : MS ISE/ Safety and Ergonomics


PHR: Project Narrative: Results from recent TCGA and pathological studies imply the oncogenic role for CD73 in breast tumor evasion and progression, although the underlying molecular mechanisms by which dysregulation of CD73 by ubiquitin-proteasome pathway contributes to breast tumor evasion, progression and metastasis remain unknown. This proposal will determine the impact of CD74 proteolytic regulation by TRIM21 in breast carcinogenesis, and further determine the clinical relevance of modulation of CD73 turnover regulation in anti-breast cancer treatment, especially for triple negative type breast cancers. Completion of this project will uncover the molecular underling of CD73 ubiquitination by TRIM21 in breast carcinogenesis and tumor microenvironment, and could provide a new strategy for breast cancer therapy by targeting TRIM21-CD73 axis.

PI_NAMEs: WAN, YONG  (contact);ZHANG, BIN

PROJECT_TERMS: Adenosine;Affect;Animal Model;Breast Cancer Cell;breast cancer progression;Breast Cancer therapy;Breast Cancer Treatment;Breast Carcinogenesis;cancer type;CD8-Positive T-Lymphocytes;Cell secretion;Cells;chemotherapy;clinically relevant;Coculture Techniques;Data;Development;Drug resistance;exhaustion;FDA approved;Feedback;Future;Goals;Human;Immune;Immune Evasion;Immune response;Immunocompetent;Immunotherapy;Impairment;In Vitro;in vivo;in vivo Model;Interferon Type II;Invaded;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Mediating;Modeling;Molecular;multicatalytic endopeptidase complex;Mus;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel therapeutic intervention;novel therapeutics;Oncogenic;Pathologic;Pathway interactions;patient derived xenograft model;Physiological;Post-Translational Protein Processing;pre-clinical;Process;Prognosis;protein complex;protein degradation;Proteolysis;Regulation;Regulation of Proteolysis;Role;Signal Transduction;T-Cell Proliferation;T-Lymphocyte;targeted cancer therapy;Testing;The Cancer Genome Atlas;therapeutic development;therapeutic target;Treatment Efficacy;Treatment Protocols;triple-negative invasive breast carcinoma;tumor;Tumor Cell Invasion;Tumor Escape;Tumor Immunity;tumor microenvironment;tumor progression;Tumor Promotion;tumor-immune system interactions;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;Work

PROJECT_TITLE: Targeting posttranslational modifications of CD73 in TNBCs

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: NARRATIVE The overarching goal of the proposed Johns Hopkins P.O.E. Total Worker Health Center in Mental Health (POE Center) is to promote worker mental health and well-being through research, education, outreach and evaluation activities that integrate the psychosocial, organizational, and environmental contexts of worker health. Given the rapid evolution of who works, how they work, and where they work—changes that have accelerated given employer and governmental response to the COVID-19 pandemic—there is a need to identify and empower resilient systems for health protection and health promotion to maintain workforce functions, health, and well-being before, during and after crises, work the POE Center will address through research, education, evaluation, communication and dissemination activities.

PI_NAMEs: DAVIS, MEGHAN F. (contact);FALLIN, M DANIELE


ORG_DEPT: BIOCHEMISTRY

PHR: Public Health Relevance Inhibition of poly(ADP-ribose) polymerase 1 (PARP1) has emerged as a promising therapeutic treatment for multiple cancer; however there is an urgent clinical need for improving the specificity of PARP1 and lowering the off-target effects and toxicity. This study proposes to screen and validate small molecule compounds that specifically inhibit the Sam68-stimulated PARP1 activation. Findings from our study may aid rational development of a new class of PARP1 inhibitors for cancer treatment.

PI_NAMEs: WAN, FENGYI  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Affect;Anemia;Animals;Attenuated;Basic Science;Biochemical;Biological Assay;Biophysics;cancer cell;cancer survival;cancer therapy;cancer type;Cancerous;Categories;Cell Death;Cell Physiology;Cells;Cellular Assay;Chemicals;chemotherapy;Clinical;Coenzymes;Colon;colon cancer cell line;Colon Carcinoma;Colonic Neoplasms;Competitive Binding;Development;Disease;DNA Damage;DNA lesion;DNA Repair;Enzyme-Linked Immunosorbent Assay;Experimental Models;experimental study;Fatigue;follow-up;gamma irradiation;gastrointestinal;genotoxicity;Health;high throughput screening;Human;imaging modality;improved;In Vitro;inhibitor;innovation;interdisciplinary approach;Interruption;Intervention;knock-down;Knock-out;Laboratories;Lead;Libraries;Malignant Neoplasms;millisecond;Mitosis;Modality;Molecular;mouse model;Mus;Myelosuppression;Nausea;Neutropenia;Niacinamide;Nicotinamide adenine dinucleotide;Normal Cell;novel;novel strategies;pharmacologic;Play;Poly(ADP-ribose) Polymerases;Polymerase;Production;Proteins;public health relevance;Radiation therapy;recruit;Regulation;repaired;Research;response;Role;screening;Signal Pathway;Signal Transduction;Signaling Molecule;Site;small molecule;small molecule inhibitor;small molecule libraries;Specificity;Therapeutic;therapeutic target;Tissues;Toxic effect;Tumor Burden;Tumor Tissue;Validation

PROJECT_TITLE: Targeting the Sam68-stimulated PARP1 activation for cancer treatment

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-F(55)R]


ORG_CITY: CHAPEL HILL

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: NARRATIVE The overarching goal of the Carolina Center for Total Worker Health (TWH) and Well-Being is to generate new knowledge and to improve worker health and well-being in North Carolina, the southeast region, and the nation. Center research activities to achieve this goal include launching pilot projects that focus on risks for adverse mental health, safety, and well-being outcomes using a TWH framework; emerging issues that can increase health safety risks for workers; and that prioritize research that is intended to protect essential workers. Other activities of the Center will build the TWH workforce capacity by mentoring a cadre of researchers in the application of the TWH framework, through education and outreach activities, and engaging workers and other key stakeholders in these efforts to ensure the work of the Center is relevant, and that findings can be translated into, and sustained, in practice arenas.

PI_NAMEs: LINNAN, LAURA A (contact)

PROJECT_TITLE: Carolina Center for Healthy Work Design and Worker Well-Being


ORG_CITY: GAINESVILLE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Diabetes data and surveillance studies among children and adolescents are significantly limited in the United State, especially in the south-east region, where diabetes was found to be the most prevalent. This proposed study will build a surveillance system in Florida to monitor the prevalence and incidence of diabetes among children and adolescents in an accurate, cost-effective, and timely fashion. This study will generate important data to study the social and behavioral determinants of health among many other potential contributing factors that results in ethnic-racial and geographic disparities of the diabetes among children and adolescents, at both individual (e.g., individual health behaviors) and contextual levels (e.g., area-level access to metabolic control programs).

PI_NAMEs: BIAN, JIANG  (contact);GUO, YI ;SHAO, HUI ;SHENKMAN, ELIZABETH A.

PROJECT_TITLE: DP20-001 Using Real-world Data to Assess the Burden of Diabetes in Children and Adolescents in Florida


ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: Federal Region VII suffers from high burdens of occupational injury and illness, poverty, unhealthy behaviors, and low healthcare access. The Healthier Workforce Center of the Midwest will address these issues through research, outreach, and education to improve worker well-being in employers of all sizes. Center efforts align with NIOSH strategic goals and priority populations, including efforts to target emerging issues among high- risk, high-need populations.

PI_NAMEs: ROHLMAN, DIANE S (contact)


ORG_CITY: CHICAGO

ORG_NAME: JESSE BROWN VA MEDICAL CENTER

PHR: Project Narrative: The goal of this proposal is to address the unmet need for a safe and efficacious version of L-asparaginase, an enzyme drug used to treat acute lymphoblastic leukemia (ALL). The clinical use of today’s FDA-approved L-asparaginases is complicated by life-threatening toxicities that result from the immunogenicity of these bacterial enzyme drugs and their L-glutaminase co-activity. Toxicity often severely limits their use in adult patients, whose cure rate is therefore significantly lower. Here we will perform IND-enabling studies of a novel L-asparaginase that is of mammalian origin (thereby reducing the immunogenicity of the drug) and that is totally devoid of the L-glutaminase co-activity (thereby reducing toxicity that arises from glutamine depletion). The safer L-asparaginase developed by this work will not only impact ALL treatment, but in addition will provide a new therapeutic and much needed option to additional hematological cancers (e.g. AML) and solid tumors (e.g. pancreatic) for which efficacy of this drug is expected based on pre-clinical studies.

PI_NAMEs: LAVIE, ARNON  (contact)

PROJECT_TERMS: acute lymphoblastic leukemia cell;Acute Lymphocytic Leukemia;Acute Myelocytic Leukemia;Address;Adult;Adult Acute Lymphocytic Leukemia;Affect;Amino Acids;anti-cancer;Antineoplastic Agents;Apoptosis;asparaginase;Asparagine;Biological;Blood;C-terminal;Cancer Patient;Canis familiaris;Catalytic Domain;Cavia;cell killing;Cells;Childhood Acute Lymphocytic Leukemia;Circulation;Clinic;Clinical;clinical efficacy;Data;Disease;Dose;drug action;drug development;drug efficacy;Drug Kinetics;Drug usage;Enzymes;Escherichia coli;Exhibits;experimental study;FDA approved;Glutaminase;Glutamine;Goals;Hematologic Neoplasms;Homologous Gene;Human;humanized mouse;Hydrolysis;Immune system;immunogenic;immunogenicity;improved;in vivo;Investigational Drugs;Investigational New Drug Application;Kinetics;Lead;Legal patent;leukemia treatment;Leukocytes;Life;Malignant neoplasm of pancreas;Malignant Neoplasms;mortality;mouse model;Mus;neoplastic cell;novel;novel therapeutics;Pancreas;pancreatic cancer patients;patient population;Patients;Pectobacterium chrysanthemi;Pegaspargase;Pharmaceutical Preparations;pharmacologic;pre-clinical;preclinical efficacy;preclinical study;preclinical toxicity;prevent;Prognosis;Property;Protocols documentation;Publishing;Rattus;Reaction;reconstitution;Reporting;Risk;Safety;Side;side effect;Site;Solid;Solid Neoplasm;Source;standard of care;Structure;success;Testing;Therapeutic;Time;Toxic effect;Toxicology;Variant;Work

PROJECT_TITLE: Pharmacological and toxicological testing of a novel L-asparaginase


NIH_SPENDING_CATS: Cancer;Dietary Supplements;Kidney Disease;Nutrition;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE Patients who are diagnosed with non-clear cell kidney cancer have very limited treatment options since there are no FDA-approved treatments for them. This application seeks to develop new treatment options in an area of unmet need by using relevant laboratory models and treated patient samples, with the goal of identifying new drug targets that can be combined to elicit deep and durable responses, and consequently extend their lives.

PI_NAMEs: THOMAS, GEORGE VICTOR (contact)

PROJECT_TERMS: Antibiotics;Arachidonic Acids;Area;Bioenergetics;Biogenesis;Biological Markers;Bypass;cancer cell;cancer therapy;Cell Death;Cell model;Cells;Clinical;clinically relevant;Combined Modality Therapy;Consumption;Diagnosis;Diet;Dietary Supplementation;Drug Kinetics;drug testing;Fatty Acids;FDA approved;Glucose;glutathione peroxidase;Glycolysis Inhibition;Goals;Growth;Half-Life;Hour;Hydrolysis;improved outcome;In Vitro;in vivo;inhibitor;kidney cell;Knowledge;Laboratories;Linoleic Acids;Lipid Peroxidation;Lipids;Malignant Epithelial Cell;Malignant Neoplasms;Metabolic;Metabolism;Mitochondria;Mitochondrial Proteins;Modeling;mouse model;Mus;new therapeutic target;Nonesterified Fatty Acids;novel;Oxidative Phosphorylation;Patient-Focused Outcomes;Patients;Peroxidases;pharmacodynamic biomarker;Pharmacotherapy;Phospholipids;Polyunsaturated Fatty Acids;Production;programs;Proto-Oncogene Proteins c-akt;Renal Carcinoma;Renal Cell Carcinoma;Reporting;Research Proposals;Respiration;response;restraint;Sampling;Signal Pathway;Signal Transduction;Survival Rate;synergism;System;Testing;Therapeutic;Therapeutic Effect;tigecycline;transcriptomic profiling;Translating;treatment strategy;tumor;tumor growth;Tumor Promotion;Unsaturated Fatty Acids

PROJECT_TITLE: Developing novel polytherapies for Non-Clear Cell Renal Cell Carcinoma

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Contraception/Reproduction;Prevention;Women's Health Research

ORG_DEPT: OBSTETRICS & GYNECOLOGY

PHR: PROJECT NARRATIVE We know that IUDs are highly effective to prevent pregnancy when used for emergency contraception (following unprotected intercourse in the last 3 days), but lack data for those who desire an etonogestrel (ENG) contraceptive implant in this situation. This proposal will identify the most effective way to start an implant for emergency contraception using a randomized controlled trial comparing pregnancy risk between those receiving the implant vs. the implant plus oral emergency contraception. Data from this project will inform clinical practice and add another option, the implant, for those desiring a long acting, highly effective contraceptive method when they present for emergency contraception.

PI_NAMEs: GAWRON, LORI MARIE (contact)

PROGRAM_OFFICER_NAME: KAUFMAN, STEVEN

PROJECT_TERMS: Address;Age;avoid pregnancy;Body mass index;Categories;Client;Clinic;Clinical;Clinical Data;clinical practice;Clinical Research;comparative efficacy;Contraceptive Agents;contraceptive efficacy;Contraceptive methods;contraceptive practice;Contraceptive Usage;cost;Counseling;Data;Eligibility Determination;emergency contraception;Enrollment;Equity;Etonogestrel;evidence base;experience;Expert Opinion;Family Planning;Fertility;follow-up;Frequencies;Goals;Guidelines;high body mass index;Hour;Human;Implant;Implantation procedure;improved;Individual;Infrastructure;interest;Intrauterine Devices;Levonorgestrel;Life;Menstruation;Methods;Monitor;Oral;Ovulation;Participant;Persons;Pharmacy facility;Placebo Control;placebo group;Placebos;Plan B;Planned Parenthood Federation of America;point of care;Postcoital Contraception;preference;Pregnancy;Pregnancy Tests;prevent;primary outcome;Progesterone;Progestins;prospective;Provider;Publications;Randomized;randomized placebo controlled trial;Randomized, Controlled Trials;Recommendation;Reporting;reproductive;Research;Risk;Role;Sales;Self Determination;Serum;sexual and reproductive health;Site;subcutaneous;Synthetic Progestogens;Time;trial comparing;Unsafe Sex;Urine;Utah;Woman;Work

PROJECT_TITLE: Generating evidence to improve same-day etonogestrel implant insertion for emergency contraception

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

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

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: PSYCHOLOGY

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

PHR: Food insecurity is associated with maladaptive outcomes in every domain of child development, with long- lasting life and health consequences, but how it undermines child development is unknown. By using ecological momentary assessment to determine the directionality and timing between food insecurity and parent and child well-being, this research will identify how food insecurity works within a family to disrupt child development. Gaining insight into these processes will help shape the most promising set of solutions for this highly significant public health threat to millions of children’s immediate and longer-term health and development.

PI_NAMEs: HINES, CAITLIN TALLENT (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: Address;Affect;Age;Awareness;Behavior;Biological Markers;career;Child;Child Behavior;Child Development;Child Rearing;Child Welfare;Communities;Data;demographics;Development;Ecological momentary assessment;Economics;Ethnic Origin;experience;Family;Family member;Fellowship;Food;Food Assistance Programs;food insecurity;food preparation;Future;Grant;Health;improved;innovation;insight;Intervention;Knowledge;Latinx;Life;Link;Measurement;Measures;Mental Depression;Mental Health;Methodology;Methods;Moods;Outcome;Parents;Pathway interactions;Pattern;Personal Satisfaction;Persons;Physiological;Physiology;Policies;Postdoctoral Fellow;primary outcome;Process;programs;Public Health;public health intervention;Race;Research;Research Personnel;Risk;Secure;Severities;Shapes;skills;Stress;System;Techniques;Testing;Time;timeline;Training;Translational Research;Work

PROJECT_TITLE: Determining pathways from food insecurity to parent and child well-being

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F16-L(21)]


NIH_SPENDING_CATS: Biotechnology;Immunotherapy

PHR: Project Narrative Streptavidin and biotin are used in many medical and research applications, but endogenous biotin interference and streptavidin’s immunogenicity attenuates its effectiveness. Biotin orthogonal streptavidin system (BOSS) is a streptavidin system that has no endogenous biotin interference and low immunogenicity. BOSS could potentially improve cancer treatment, disease diagnostics and scientific assays.

PI_NAMEs: DRAPER, STEVEN  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Academia;Acceleration;Affinity;Amino Acids;Animal Disease Models;Antibodies;antibody conjugate;Attenuated;Binding;Biological;Biological Assay;Biomedical Research;Biotin;Biotinylation;Calorimetry;cancer therapy;career;Cell surface;Cells;chemical conjugate;chemical synthesis;Chemicals;Chemistry;chemotherapy;Circular Dichroism;Circulation;Communities;Crystallography;Cultured Cells;Diagnostic;Diagnostic tests;Disease;disease diagnostic;Drug Kinetics;Effectiveness;enantiomer;experimental study;Fellowship;Fluorescence;Fluorescence Microscopy;fluorophore;Foundations;Future;Generations;Glycosphingolipids;Half-Life;Image;Imaging ligands;Immune system;Immunoassay;immunogenic;immunogenicity;Immunoglobulin Fragments;Immunotherapy;improved;Label;Laws;Ligation;Measures;Medical;Methods;Molecular Sieve Chromatography;Mus;Nature;neoplastic cell;Neuroblastoma;neuroblastoma cell;novel;peptide chemical synthesis;Peptide Hydrolases;Peptide Synthesis;Pharmaceutical Preparations;Phase;Phase I Clinical Trials;Procedures;Process;Property;Proteins;Publishing;Reagent;Recombinants;Reporting;Research;Rosaniline Dyes;Science;side effect;Solid;Specificity;Streptavidin;success;System;Testing;Therapeutic;Time;Titrations;tool;tumor;Tumor Antigens;Xenograft procedure

PROJECT_TITLE: Biotin Orthogonal Streptavidin System (BOSS) for Drug Pre-Targeting


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Ischemic stroke is a devastating neurological disease affecting millions of Veterans. There is now an urgent need to understand the underlying mechanisms of stroke brain injury and to develop therapeutics against stroke brain injury. Stroke leads to brain ischemia-reperfusion injury (IRI). Currently, there are no neuroprotective or anti-IRI drugs available for Veterans who suffer from stroke. This proposal will use a state-of-the-art animal model to study the underlying mechanisms of stroke brain injury and to study a potential therapy for minimizing post-stroke damage. If successful, this anti-stroke drug discovery program can be applied to fulfill the VA’s mission in alleviating Veterans’ suffering from the sequelae of stroke.

PI_NAMEs: HU, BINGREN  (contact)

PROJECT_TERMS: Abate;acute stroke;Affect;Animal Model;Animals;Autophagocytosis;Behavioral;Biological Assay;Brain;Brain Injuries;Brain Ischemia;Categories;Cell Culture Techniques;Cessation of life;Confocal Microscopy;cytokine;Dissociation;Double-Blind Method;drug discovery;EIF4EBP1 gene;Enzymes;Eukaryotic Initiation Factors;Event;Excision;FRAP1 gene;Future;Genes;genetic regulatory protein;Genetic Transcription;Goals;Hemorrhage;high throughput technology;Hydrophobicity;improved;Infarction;Inflammation;inhibitor;Injections;Injury;Ischemia;Ischemic Brain Injury;Ischemic Stroke;Laboratories;Leucine;Messenger RNA;Mission;Modeling;Molecular Chaperones;mortality;mouse model;Mus;Natural regeneration;Nervous System Disorder;Neurologic Deficit;neuron loss;Neurons;neuroprotection;novel;Paper;Pathologic;Pathway interactions;Peptide Initiation Factors;Performance;Perfusion;Pharmaceutical Preparations;Phase;Phosphorylation;polypeptide;Polyribosomes;post stroke;Process;programs;protein aggregation;Proteins;Publishing;Randomized;Recovery;Reperfusion Injury;Reperfusion Therapy;Research;response;Ribavirin;Ribosomes;Role;side effect;Stress;Stroke;stroke model;stroke patient;System;systemic inflammatory response;targeted agent;Testing;Therapeutic;therapeutic target;Time;TLR4 gene;transcription factor CHOP;Translations;Up-Regulation;Veterans;Western Blotting

PROJECT_TITLE: Novel Anti-Stroke Agents Targeting Toxic Protein Aggregation


PHR: Veterans with inflammatory bowel disease (IBD) have a 4-fold higher risk of developing colorectal cancer than those without IBD. While current practice advises follow-up examinations at fixed intervals for early detection of cancer, this “one-size-fits-all” approach is not appropriate for all patients with IBD. Moreover, it is not supported by our modern knowledge of how cancer evolves from normal colon tissue. Unnecessary colonoscopies performed in patients with IBD at low-risk of developing cancer are costly (>$5million spent per year) and invasive, while patients at high-risk of cancer are not seen frequently enough. Mathematical models of cancer evolution incorporating patient-specific clinical and genomic data will revolutionize clinical prediction of colorectal cancer development in patients with IBD. These models will enable personalized care for each Veteran to effectively prevent cancer and improve patient lives.

PI_NAMEs: CURTIUS, KATHLEEN M. (contact)

PROJECT_TERMS: Age;Assessment tool;Barrett Esophagus;Biological Markers;Biophysics;Biopsy;Calibration;Cancer Model;cancer prevention;cancer risk;carcinogenesis;Cirrhosis;Clinical;Clinical Data;clinical data warehouse;clinical decision support;clinical predictors;cohort;Colitis;Colitis associated colorectal cancer;Colon;Colonic Diseases;Colonoscopy;Colorectal Adenoma;Colorectal Cancer;colorectal cancer prevention;colorectal cancer progression;colorectal cancer screening;Communication;computerized tools;cost;Dangerousness;Data;data modeling;design;Detection;Development;Diagnosis;disease diagnosis;DNA Sequence Alteration;Dysplasia;Early Diagnosis;early screening;epidemiologic data;Epithelium;Esophageal Adenocarcinoma;Evolution;flexibility;follow-up;Foundations;Future;gastric intestinal metaplasia;genetic predictors;Genetic Risk;Genome;genome sequencing;genome wide association study;genomic data;Genomics;Goals;Guidelines;health care service;Hereditary Nonpolyposis Colorectal Neoplasms;high risk;High-Risk Cancer;improved;Incidence;indexing;Individual;individual patient;Inflammatory Bowel Diseases;Inherited;innovation;Intercept;Intervention;Knowledge;Lesion;Life Style;Malignant Neoplasms;Maps;mathematical methods;mathematical model;Mathematics;Measurement;Modeling;models and simulation;Modernization;Molecular;mortality;multiple omics;multiscale data;novel;Onset of illness;Outcome;Pancreas;Pathology;Patients;personalized care;polygenic risk score;Population;Population Programs;Positioning Attribute;precision medicine;Predictive Analytics;predictive modeling;predictive tools;premalignant;Prevalence;prevent;Process;prognostic;programs;Prospective Studies;Recommendation;Research;Risk;risk prediction;risk variant;Schedule;screening;Screening for cancer;shared decision making;simulation;Statistical Models;success;support tools;surveillance data;Surveillance Program;surveillance strategy;Techniques;Time;Tissues;tool;Translating;treatment as usual;trend;Ulcerative Colitis;Update;Veterans;web-based tool;whole genome;Work

PROJECT_TITLE: Mathematical Optimization of Surveillance Ages to Intercept colitis-associated Colorectal cancer (MOSAIC)


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_DEPT: PHYSIOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE Dopamine signaling is thought to promote movement by differentially modulating the activity of different neuron types in the striatum, a process that goes awry in movement disorders such as Parkinson’s disease. However, the exact relationship between dopamine release, neuronal activity and movement are not fully understood. We have discovered that motor learning differentiates how the striatum’s different neurons encode movement and will elucidate the involvement of striatal dopamine signaling and synaptic plasticity in this process.

PI_NAMEs: PARKER, JONES G (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Ablation;Address;Axon;Brain;cell type;Cells;Color;Conflict (Psychology);Corpus striatum structure;Data;Development;Dopamine;Dopamine D1 Receptor;Dopamine D2 Receptor;dopamine system;dopaminergic neuron;Electrophysiology (science);experimental study;Gene Expression;Image;imaging approach;imaging study;Immediate-Early Genes;Impairment;in vivo;in vivo imaging;learned behavior;Learning;Lesion;Link;Locomotion;Measurement;Mental disorders;Modeling;Motion;Motor;motor control;motor learning;Movement;Movement Disorders;multiphoton imaging;Nervous System Disorder;neural;neuroimaging;neuronal excitability;Neurons;Optics;Parkinson Disease;pars compacta;patch clamp;permissiveness;postsynaptic;predictive modeling;presynaptic;Probability;Process;response;Role;Running;Signal Transduction;Spatial Distribution;Speed;Stimulus;Substantia nigra structure;Synapses;Synaptic plasticity;Testing;Time;tool;Training;transmission process;two-photon;Work

PROJECT_TITLE: Dopamine, Synaptic Plasticity and Striatal Ensemble Dynamics Underlying Motor Learning

STUDY_SECTION: SMN

STUDY_SECTION_NAME: Sensory-Motor Neuroscience Study Section[SMN]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Atherosclerosis;Biomedical Imaging;Breast Cancer;Cancer;Cardiovascular;Clinical Research;Estrogen;Heart Disease;Heart Disease - Coronary Heart Disease;Menopause;Women's Health Research

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: Narrative New treatment recommendations for premenopausal women with high or intermediate risk hormone receptor breast cancer now include ovarian function suppression, to induce early menopause combined with anti-estrogen therapy resulting in near-complete estrogen deprivation. This abrupt menopause induction together with anti-estrogen therapy improves survival from cancer yet also places these women at risk of organ damage, including heart toxicity. Our pilot study suggests that asymptomatic declines in heart perfusion are observed over several months on this therapy. In this work we will study women with serial heart imaging to more fully understand the impact of this treatment on small and large heart vessels, as well as to study if there are patient characteristics, blood biomarkers or electrocardiogram changes which can predict who is at greatest risk for heart damage from near-complete estrogen deprivation.

PI_NAMEs: JORDAN, JENNIFER HAWTHORNE;THOMAS, ALEXANDRA  (contact)

PROGRAM_OFFICER_NAME: DESVIGNE-NICKENS, PATRICE

PROJECT_TERMS: Age;Angiography;Anti-estrogen Therapy;Antineoplastic Agents;Aorta;ascending aorta;Atherosclerosis;Biological Markers;Blood;Blood Pressure;Blood Vessels;calcification;Cancer Burden;cancer survival;cancer therapy;cardiac magnetic resonance imaging;Cardiotoxicity;Cardiovascular Diseases;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Characteristics;Clinical;Coronary Arteriosclerosis;coronary calcium scoring;demographics;deprivation;Descending aorta;Development;EFRAC;Electrocardiogram;Endothelium;Estrogens;Ethnic Origin;experience;Goals;Heart;heart damage;heart imaging;High Risk Woman;Hormone Receptor;hormone receptor-positive;improved;Incidence;Inflammation;Knowledge;Left;Left Ventricular Mass;Left ventricular structure;Malignant Breast Neoplasm;Maps;Measurement;Measures;Menopause;multidisciplinary;Myocardial;Myocardial perfusion;Natural History;Organ;Ovarian;Patients;Perfusion;perfusion imaging;Physiologic pulse;Pilot Projects;potential biomarker;pre-clinical;predictive tools;Premature Menopause;Premenopause;Prevalence;pro-brain natriuretic peptide (1-76);Race;Recommendation;Recurrence;Regimen;Risk;Risk Factors;Serum;social health determinants;standard of care;Stress;Stroke Volume;Testing;Time;tool;Toxic effect;Treatment-related toxicity;trend;triple-negative invasive breast carcinoma;Troponin;United States;vascular injury;Ventricular;Woman;women's diagnosis;Women's Health;Women's study;Work;X-Ray Computed Tomography

PROJECT_TITLE: Cardiovascular Impact of Near-complete Estrogen Deprivation for Breast Cancer

STUDY_SECTION: CCHS

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


NIH_SPENDING_CATS: Biotechnology;Chronic Obstructive Pulmonary Disease;Infectious Diseases;Lung;Tobacco;Tobacco Smoke and Health

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Chronic obstructive pulmonary disease is a debilitating disease, affecting ~5% of the US population, ranking third as a cause of mortality, with the commonest cause being chronic cigarette smoke exposure. This exposure leads to malfunction of cilia, hair-like projections lining the airway tract that beat in coordinated fashion to sweep inhaled pollutants and pathogens away from the lungs, as well as generation of reactive oxygen species that lead to mitochondrial dysfunction and eventually cell death. In this application, we are proposing to use a small molecule to enhance cilia function and utilize lung-targeting peptides to rescue mitochondria, thereby targeting the underlying pathophysiology of a disease that has not seen any new drug development in over two decades.

PI_NAMEs: ZAHID, MALIHA  (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Affect;Affinity;airway obstruction;Alanine;Alveolar;Amino Acids;Apoptotic;Area;Arginine;Attenuated;Binding;Biodistribution;Biological Assay;bronchial epithelium;Bulla;burden of illness;Cardiac;Cell Culture Techniques;Cell Death;Cell Density;Cell Line;Cell Nucleus;Cell surface;Cell Surface Proteins;Cells;Chronic;Chronic Obstructive Pulmonary Disease;cigarette smoke-induced COPD;Cilia;cilium biogenesis;cilium motility;comparison control;Coughing;cytokine;Cytolysis;Disease;disease model;drug development;Embryo;Epithelial Cells;Epithelium;esterase;Esters;exposure to cigarette smoke;FDA approved;fluid flow;Frequencies;Functional disorder;gamma secretase;Generations;Genus Hippocampus;Goals;Goblet Cells;Grant;Hair;Harvest;Heart;High Prevalence;Hospitalization;Human;Hyperplasia;Image;imaging system;Impairment;improved;in vivo;in vivo imaging system;Incubated;Inflammatory Infiltrate;Inhalation;inhibitor;Injections;interest;Intravenous;knock-down;Label;Length;Ligands;Lower Respiratory Tract Infection;Lung;Measures;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Morbidity - disease rate;Morphology;mortality;Mucociliary Clearance;Mucous body substance;Mus;mutant;Nasal Epithelium;notch protein;novel;novel therapeutics;Organ;Oxygen;pathogen;Pathway interactions;Penetration;Peptides;Peripheral;peroxiredoxin;Ploidies;pollutant;Population;Positioning Attribute;Predisposition;Production;Proteins;Reactive Oxygen Species;Recurrence;recurrent infection;Reduced Glutathione;Scanning;Serine;Shortness of Breath;Small Interfering RNA;small molecule;smoke-induced COPD;Structure of parenchyma of lung;Surface;Technology;Testing;Therapeutic;thioredoxin peroxidase;Time;Tissues;Trachea;Tracheobronchial;transcription factor;Trees;Triceps Brachii Muscle;Tubulin;uptake;vector;Work;Xenopus

PROJECT_TITLE: Targeting Underlying Pathophysiological Mechanisms to Develop Novel Therapies for Chronic Obstructive Lung Disease

STUDY_SECTION: GDD

STUDY_SECTION_NAME: Gene and Drug Delivery Systems Study Section[GDD]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Neurosciences;Rare Diseases

ORG_CITY: DALLAS

ORG_DEPT: NEUROLOGY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: EGFR promotes the growth of malignant cells. However, inhibition of the EGFR does not inhibit tumor growth in glioblastoma (GBM). We aim to improve understanding of mechanisms of resistance to EGFR inhibition in GBM and examine a strategy to overcome the resistance of glioma cells to EGFR inhibition.

PI_NAMEs: HABIB, AMYN  (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: Address;Biological;cancer cell;cancer therapy;Cell Culture Techniques;Cell Death;Cells;Cellular Stress;Chemotherapy and/or radiation;Clinical;clinically relevant;Colon Carcinoma;Data;Disease;effective therapy;EGFR gene;EGFR Gene Amplification;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;epidermal growth factor receptor VIII;Erlotinib;Estrogen Receptors;Experimental Models;Failure;FDA approved;Frequencies;Gene Mutation;Genes;Genetic Transcription;Glioblastoma;Glioma;Gliomagenesis;Growth;Homeostasis;Immunotherapy;improved;inhibitor;Interruption;isoniazid;Ligands;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Mediator;Meningeal Tuberculosis;Modeling;Mus;mutant;Mutation;neoplastic cell;Oncogenes;Oncogenic;overexpression;Pathway interactions;Patients;Play;pre-clinical;Prevalence;prevent;Prognosis;Radiation therapy;receptor expression;Receptor Inhibition;Receptor Signaling;Recommendation;Reporting;Resistance;resistance mechanism;response;Role;Signal Transduction;Tamoxifen;targeted treatment;Testing;therapy resistant;TNF gene;transcription factor;Transcriptional Activation;transcriptome;Translations;Trastuzumab;tumor;tumor growth;Tumor Tissue;Work

PROJECT_TITLE: The role of Nrf2 in mediating resistance to EGFR inhibition in glioblastoma

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Genetics;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: OKLAHOMA CITY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Pancreatic cancer (PC) is one of the most difficult human cancers to treat due to the inability to detect disease at an early stage and the lack of effective therapies. This proposal aims to study the role of ZIP4 and ZEB1, potential new markers and therapeutic targets in pancreatic cancer, in the biology of these tumors. This study will lead to meaningful advances for understanding this horrible disease and help in the development of novel therapeutic and diagnostic approaches for this malignancy.

PI_NAMEs: LI, MIN  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Address;Biological Assay;Biology;Cell Adhesion;cell motility;Cells;Complex;Data;Death Rate;Development;diagnostic development;Diagnostic Procedure;diagnostic strategy;Disease;Drug resistance;effective therapy;Foundations;gemcitabine;Gene Expression Regulation;Genetic Engineering;Genetic Transcription;Genetically Engineered Mouse;Growth;Human;improved;Integrin-mediated Cell Adhesion Pathway;Integrins;Invaded;knock-down;Knock-out;KPC model;Luciferases;Malignant neoplasm of pancreas;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Methodology;migration;Modeling;Molecular;molecular marker;mouse model;Neoplasm Metastasis;new therapeutic target;novel;novel diagnostics;novel marker;novel therapeutics;Oncogenic;overexpression;pancreatic cancer cells;pancreatic cancer model;Pathway interactions;Pharmaceutical Preparations;promoter;Property;Reporter;Resistance;Role;Signal Pathway;Signal Transduction;Survival Rate;targeted treatment;Technology;therapeutic target;transcription factor;Transcriptional Regulation;tumor;Tumor Biology;tumor growth;tumor progression;tumorigenesis;Up-Regulation;Xenograft procedure;Zinc;zinc-binding protein

PROJECT_TITLE: Role of Zinc Dependent EMT-Transcription Factors (EMT-TF) in Pancreatic Cancer Metastasis

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: PROJECT NARRATIVE Bacterial biofilms exhibit multicellular behaviors that allow them to tolerate antibiotics and thrive in low nutrient environments. The goal of this proposal is to uncover how these collective behaviors emerge from single-cell-level properties and cell-to-cell interactions. This work is relevant to the NIH mission because it will lay foundations for new ways to target emergent behaviors that make biofilms extremely resilient.

PI_NAMEs: LARKIN, JOSEPH W (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: antibiotic tolerance;Award;Bacillus subtilis;Bacteria;Behavior;cell behavior;Cell Communication;Cells;Communities;Crowding;Data;Development;Devices;Environment;Exhibits;Foundations;Gene Expression;Gene Expression Regulation;Genes;Goals;Heterogeneity;Hospitals;Image;Infection;Learning;Measurement;Microbe;Microbial Biofilms;Mission;Modeling;Motility;novel;Nutrient;Pattern;Penetration;Pharmaceutical Preparations;Phenotype;Physics;Planet Earth;Polymers;polymicrobial biofilm;Property;resilience;System;Transistors;United States National Institutes of Health;Work

PROJECT_TITLE: From cell-to-cell heterogeneity to collective behaviors in bacterial biofilms

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Physical Activity;Physical Rehabilitation;Rehabilitation

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE The lack of accessible therapies amenable for application in the home setting is a major obstacle for treating patients who suffer from lower-extremity peripheral artery disease (PAD). The goal in this proposal is to evaluate the benefits of home-based, leg heat therapy (HT) on lower-extremity functioning and quality of life in patients with PAD. Since this intervention is non-invasive, non-pharmacological and widely accessible, there is high potential for this work to rapidly translate into clinical practice and result in significant improvements in patients’ lives. Bruno Roseguini, Ph.D.

PI_NAMEs: ROSEGUINI, BRUNO T (contact)

PROGRAM_OFFICER_NAME: NELLISSERY, MAGGIE JACOB

PROJECT_TERMS: Acceleration;Activities of Daily Living;Address;Affect;American;Angiogenic Factor;Area;arterial spin labeling;Atherosclerosis;Atrophic;Bathing;Biological;Biopsy;Biopsy Specimen;Blood capillaries;Blood flow;Buttocks;Capillarity;Cardiovascular system;Clinical;clinical practice;combat;Controlled Clinical Trials;Coupled;Custom;Data;Diagnosis;diet-induced obesity;Doctor of Philosophy;Double-Blind Method;Engineering;Equilibrium;Event;evidence base;exercise intolerance;exercise regimen;experimental study;Exposure to;Fatty acid glycerol esters;follow-up;Foundations;functional decline;functional disability;functional restoration;Gait abnormality;Goals;Growth;Heating;Home;Human;Immersion;Immunohistochemistry;improved;Individual;Infiltration;Intervention;Ischemia;Isotonic Exercise;Leg;Link;Lower Extremity;Magnetic Resonance Imaging;meter;Modeling;Morphology;mortality;Muscle;Muscle Fatigue;muscle form;muscle strength;Muscular Atrophy;Myalgia;National Institute on Aging;novel;novel strategies;novel therapeutic intervention;older patient;Outcome Study;Pain;Painless;Participant;Pathway interactions;Patient Compliance;Patients;Perceived quality of life;Performance;Perfusion;Peripheral arterial disease;Persons;Physical Function;Physical Performance;Pilot Projects;pilot trial;placebo group;portability;Pre-Clinical Model;Pump;Quality of life;Randomized;randomized, clinical trials;Recovery;Reporting;Research;Resistance;Safety;secondary outcome;sedentary;Skeletal Muscle;Supervision;System;Therapeutic;Therapeutic heat application;Therapy trial;Thigh structure;Tissues;tool;Translating;Translations;Walking;walking performance;walking speed;Water;Work

PROJECT_TITLE: Leg heat therapy to improve functional performance in peripheral artery disease


NIH_SPENDING_CATS: Behavioral and Social Science;Biotechnology;Brain Disorders;Epilepsy;Neurodegenerative;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative Epilepsy is a common neurological disorder afflicting nearly 3 million Americans. Given that loss or reduction of inhibitory synaptic transmission in hippocampus is one potential mechanism resulting in emergence of epilepsy, a method to generate new hippocampal interneurons could have direct therapeutic consequences. Using porcine embryonic neural progenitor cells and rodent model of temporal lobe epilepsy or epilepsy-autism disorder we propose to develop a novel interneuron-based cell therapy.

PI_NAMEs: BARABAN, SCOTT C (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: acquired epilepsy;Address;Adult;Age;American;Animal Model;Animals;Area;autism spectrum disorder;behavior test;Behavioral;Behavioral Assay;Benchmarking;Brain;Brain region;brain tissue;Calcium;Cell model;Cell Therapy;Cell Transplantation;Cells;Central Nervous System;Childhood;Chronic;Clinical;Cognitive;Collaborations;comorbidity;confocal imaging;Confocal Microscopy;cost;Data;density;Development;Disease;donor stem cell;Drug resistance;Electroencephalography;Electrophysiology (science);Embryo;embryonic stem cell;Epilepsy;Evaluation;Exhibits;Family suidae;gamma-Aminobutyric Acid;Generations;Genetic;Goals;Harvest;Hippocampus;Image;imaging modality;Imaging technology;Immunohistochemistry;improved;in silico;In Vitro;in vivo;inhibitory neuron;Inhibitory Synapse;Interneurons;Intractable Epilepsy;Investigation;Knockout Mice;life span;Medial;Mediating;Methods;migration;Modeling;Monitor;mouse model;Mus;National Institute of Neurological Disorders and Stroke;neocortical;Neonatal;nerve stem cell;Nervous System Disorder;Neurologic;Neurons;novel;novel therapeutics;optogenetics;patch clamp;Persons;Phenotype;Pilocarpine;Population;pre-clinical;prevent;Procedures;progenitor;programs;Protocols documentation;Quality of life;Research;Rodent;Rodent Model;Seizures;side effect;social;Source;stem cell model;stem cell therapy;Stem cell transplant;stem cells;Symptoms;Synapses;synaptic inhibition;Synaptic Transmission;Techniques;Temporal Lobe Epilepsy;Therapeutic;tool;Translations;Transplantation;transplantation therapy;two-photon;United States National Institutes of Health;Visualization;Work;Xenograft procedure

PROJECT_TITLE: An Interneuron-based Cell Therapy for Epilepsy

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: Aurora

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Baker, UC Denver – School of Medicine – Dept. of Immunology and Microbiology This projects aims to gain better understating of T cell reactivity in the context of type 1 diabetes. Knowledge from these studies may improve our understanding of the underlying autoimmune disease process and may ultimately lead to antigen specific therapies that may change the course of this difficult clinical disease.

PI_NAMEs: BAKER, ROCKY LEE (contact)

PROGRAM_OFFICER_NAME: MORRIS FEARS, MARGARET A

PROJECT_TERMS: Antigens;Autoantibodies;Autoantigens;Autoimmune Diabetes;Autoimmune Diseases;autoimmune pathogenesis;Autoimmunity;autoreactive T cell;Beta Cell;Biological Markers;C-Peptide;CD4 Positive T Lymphocytes;Cells;Chromogranin A;Clinical;cohort;Data;design;Diabetes Mellitus;Diagnosis;Disease;disease natural history;effector T cell;enzyme linked immunospot assay;Family;Generations;Goals;Hot Spot;Human;human disease;Hybrids;Immune;Immunology;improved;Inbred NOD Mice;Individual;Inflammatory;Injury;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;Investigation;islet;islet amyloid polypeptide;islet cell antibody;Knowledge;Left;Ligands;medical schools;Microbiology;mouse model;Mus;Natural History;Nature;neoantigens;neuropeptide Y;Onset of illness;Organ;Organ Donor;Patients;Peptide Fragments;Peptides;Peripheral Blood Mononuclear Cell;Phenotype;Play;Post-Translational Protein Processing;predictive marker;Process;prospective;protein aminoacid sequence;Proteins;Publishing;Research;Residual state;response;Risk;Role;Secretory Vesicles;single-cell RNA sequencing;Site;Specificity;Structure of beta Cell of islet;T cell response;T-Lymphocyte;Testing

PROJECT_TITLE: Responses to Hybrid Insulin Peptides as Biomarkers of Disease Activity in Human Type 1 Diabetes

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Pediatric;Prevention

ORG_CITY: ATLANTA

ORG_DEPT: GENETICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: NARRATIVE Cleft palate is a common structural birth defect and accounts for ~33% of all cases of orofacial clefts (OFCs). Cleft palate is highly heritable, suggesting it can be caused by genetic factors. However, in contrast to other types of OFCs (e.g., cleft lip and cleft lip with cleft palate), genetic studies of cleft palate have been sparse and much of the genetic risk is still unknown. The goal of the current study is to comprehensively identify genetic risk variants for cleft palate using whole genome sequencing of CP trios and transcriptome data from human palate tissue.

PI_NAMEs: LESLIE-CLARKSON, ELIZABETH JANE (contact)

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: Address;Affect;ATAC-seq;Benchmarking;Biological;ChIP-seq;Cleft Lip;Cleft lip with or without cleft palate;Cleft Palate;Clinical;Code;cohort;Collection;comorbidity;Congenital Abnormality;congenital anomaly;congenital heart abnormality;craniofacial;Data;data integration;Data Set;de novo mutation;Dental;Development;developmental disease;Developmental Process;Diagnosis;Epidemiology;Etiology;Face;Family;Family Study;feeding;Female;Financial Hardship;First Degree Relative;functional genomics;gene discovery;Gene Frequency;Genes;Genetic;genetic architecture;genetic predictors;Genetic Predisposition to Disease;Genetic Risk;Genetic study;genetic variant;genome sequencing;genome wide association study;genomic data;Genomics;Goals;Hearing;Hearing problem;heart defect;Heritability;Heterogeneity;high risk;high risk population;Human;human data;Human Genetics;human RNA sequencing;improved;Individual;Inherited;insight;Knowledge;Lip structure;male;Mediating;Meta-Analysis;Molecular;multi-ethnic;Mus;Nasal cavity;Neurodevelopmental Disorder;novel;Nucleotides;Operative Surgical Procedures;Oral cavity;orofacial cleft;Palate;palate repair;Parents;Pathway interactions;Phenotype;pleiotropism;Population;Population Heterogeneity;precision genetics;Prevention;Prognosis;rare variant;recruit;Recurrence;repaired;Research;Resources;Risk;risk variant;Sampling;Sex Bias;single cell sequencing;Soft Palate;Speech;Structural Congenital Anomalies;Structure;Syndrome;Techniques;Tissues;transcriptome;transcriptome sequencing;transcriptomics;Translating;Untranslated RNA;Variant;whole genome

PROJECT_TITLE: Genomics of Cleft Palate

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Patient Safety;Pediatric;Prevention;Rehabilitation

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Bedrest, deep sedation, and delirium are common in the pediatric intensive care unit (PICU) and can have long-lasting negative effects for children and their families. Early mobility and exercise in the intensive care unit can improve outcomes for adult patients, but the effects in children are unknown. The purpose of this study is to evaluate the potential benefits of a team-based strategy to improve sedation practices and prevent delirium with the goal of increasing early mobility in the PICU.

PI_NAMEs: KUDCHADKAR, SAPNA R (contact)

PROGRAM_OFFICER_NAME: JENKINS, TAMMARA L

PROJECT_TERMS: 2 year old;Absence of pain sensation;Admission activity;Adoption;Adult;Affect;Bed rest;Biometry;Breathing;Caring;Child;Child health care;Childhood;Clinical;Clinical effectiveness;clinical practice;Clinical Trials;Cognitive;Communities;Community Hospitals;contextual factors;Critical Care;critical developmental period;Critical Illness;Critically ill children;Data;Death Rate;Delirium;effectiveness evaluation;Elements;Engineering;Exercise;experience;Family;Focus Groups;functional decline;functional improvement;functional status;Goals;hazard;Health system;high risk;Home;hospital readmission;Hospitals;Human;Iatrogenesis;Immobilization;Impairment;implementation strategy;improved;improved outcome;Intensive Care Units;Interdisciplinary Study;Intervention;intervention delivery;Investments;Lead;Leadership;Mechanical ventilation;Medical;Methods;Morbidity - disease rate;mortality;Muscle Weakness;novel;Occupational Therapist;Occupational Therapy;Outcome;Pain management;Patient Admission;Patient-Focused Outcomes;Patients;Pediatric Intensive Care Units;Phase;physical therapist;Physical therapy;Pilot Projects;pilot trial;Prevalence Study;prevent;Prevention;primary outcome;process evaluation;psychologic;Public Health;Qualitative Research;Randomized;randomized trial;Randomized, Controlled Trials;Rehabilitation therapy;Research;Risk;Safety;safety and feasibility;safety testing;Sedation procedure;Site;Sleep;Sleep disturbances;Surveys;Survivors;System;Technology;Testing;therapy design;treatment as usual;United States;Work

PROJECT_TITLE: Clinical Effectiveness of the "PICU Up!" Multifaceted Early Mobility Intervention for Critically Ill Children:  A pragmatic, stepped-wedge trial

STUDY_SECTION: NRCS

STUDY_SECTION_NAME: Nursing and Related Clinical Sciences Study Section[NRCS]


ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Program Narrative  Despite many recent advances in treatment of prostate cancer, it remains a major cause of cancer-related death in American men. The investigators in our multi-disciplinary team will apply their complementary expertise to investigate fundamental mechanisms of prostate cancer progression, metastasis, and treatment resistance in order to provide new insights into molecular pathways and targets for improved therapeutics.

PI_NAMEs: SHEN, MICHAEL M. (contact)

PROGRAM_OFFICER_NAME: HILDESHEIM, JEFFREY

PROJECT_TERMS: Abate;Affect;American;Androgen Antagonists;Androgen Receptor;Androgens;Anti-androgen Therapy;Biological Assay;Biometry;bone;Cancer Etiology;Candidate Disease Gene;Castration;cell type;Cells;cellular imaging;Cessation of life;cofactor;data management;Data Set;deprivation;Development;Disease Resistance;Epithelial-Stromal Communication;Genetically Engineered Mouse;Group Meetings;Health;Heterogeneity;Human;human tissue;Image Analysis;Immune;improved;Infiltration;insight;Institution;International;Intrinsic factor;Investigation;Joints;lens;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Medical center;Medicine;member;Memorial Sloan-Kettering Cancer Center;men;Metastatic Neoplasm to the Bone;Modeling;Molecular;molecular pathology;multidisciplinary;multiparametric imaging;Mus;Myelogenous;Neoplasm Metastasis;neoplastic cell;neuroendocrine differentiation;Neuroendocrine Prostate Cancer;Neurosecretory Systems;new technology;New York City;novel strategies;Office of Administrative Management;Organogenesis;Organoids;Pathologic;Pathology;Pathway interactions;Population;programs;Prostate;Prostate Adenocarcinoma;prostate cancer metastasis;prostate cancer progression;Prostate Cancer therapy;Prostatic Neoplasms;Publications;Regulation;Research Personnel;Resistance;Resources;response;Retrieval;Role;Running;Sampling;Services;Signal Transduction;single cell analysis;single cell sequencing;single-cell RNA sequencing;Specific qualifier value;Structure;System;Systems Analysis;technology development;Therapeutic;therapy resistant;Tissue Microarray;Tissue Sample;Tropism;tumor;tumor microenvironment;tumor progression;tumor-immune system interactions;Universities

PROJECT_TITLE: Investigating cell-intrinsic and extrinsic interactions in prostate cancer at the single cell level


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

PHR: Project Narrative  Our proposed studies of the tumor microenvironment in prostate cancer are based on accumulating evidence that immune cells and stromal cells surrounding the tumor provide important signals that can accelerate progression of the disease. Furthermore, the primary treatment for advanced prostate cancer (hormone therapy) affects these immune and stromal cells in addition to the tumor cells, and we have limited insight into how these unintended treatments effects influence clinical outcome. The work in this Project will provide greater clarity on how the tumor microenvironment enhances tumor growth and help pave the way to better treatments, including improved use of hormone therapy.

PI_NAMEs: SAWYERS, CHARLES L. (contact)

PROJECT_TERMS: Abate;Acceleration;Address;advanced disease;advanced prostate cancer;Affect;Alleles;Androgen Antagonists;Androgen Receptor;antagonist;Anti-androgen Therapy;Antibodies;Area;Biological Assay;Biology;Blocking Antibodies;Bone Marrow;Castration;Cells;Clinic;Clinical;Clinical Research;Collaborations;Combined Modality Therapy;CSF1R gene;cytokine;Data;data management;Data Set;Disease;Disease Progression;drug efficacy;Drug Targeting;Ensure;Epithelial Cells;Epithelium;experience;FDA approved;Fibroblasts;Fluorescence;Gene Expression Profile;Gene Expression Profiling;Genetically Engineered Mouse;Genomic approach;Genomics;Hormonal;hormone therapy;Hormone use;Human;human tissue;Immune;immune cell infiltrate;Immune checkpoint inhibitor;improved;in vivo;Infiltration;Inflammatory;insight;Invaded;Investigation;Laboratory Finding;Large-Scale Sequencing;Localized Disease;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;Mediating;Mesenchymal;Metastatic Neoplasm to the Bone;Metastatic Prostate Cancer;Modeling;Mus;Myelogenous;Myeloid Cells;Myeloid-derived suppressor cells;Neoplasm Metastasis;neoplastic cell;neuroendocrine differentiation;Neurosecretory Systems;novel;Organoids;Outcome;Pathogenesis;Pathway interactions;Play;Population;programs;Prostate;Prostate Adenocarcinoma;prostate cancer model;prostate cancer progression;Prostatic Neoplasms;Proteins;Publishing;Receptor Inhibition;Receptor Signaling;recombinase;reconstitution;Reporter;resistance mechanism;response;Role;Sampling;Signal Transduction;single cell sequencing;single cell technology;single-cell RNA sequencing;Sorting;Stromal Cells;synergism;T-Lymphocyte;Technology;Tissue Recombination;tissue resource;Tissue Sample;tool;Translating;treatment effect;treatment response;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;Tumor-infiltrating immune cells;Uncertainty;WNT Signaling Pathway;Work

PROJECT_TITLE: Project 1: Investigation of immune and stromal factors that promote prostate adenocarcinoma progression and castration response


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Prevention;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PHR: Project Narrative Over 200 million contact sport athletes and military personnel are at risk of developing chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with exposure to repetitive head trauma with no current diagnostic or therapeutic strategies. This proposal will examine a promising potential mechanism of disease, microglial lysosomal dysfunction, to better understand its contribution to CTE pathology onset and progression. The proposed research is highly relevant to public health because it will contribute to our understanding of how repetitive head trauma can lead to CTE and follows the NIH mission to develop novel diagnostic biomarkers and therapies to lessen the morbidity and mortality of neurodegenerative diseases.

PI_NAMEs: BUTLER, MORGANE LMD (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Address;Age;Alleles;Alzheimer's Disease;Autopsy;Bioinformatics;Blood Vessels;Brain;brain tissue;Cathepsins B;Cd68;chronic traumatic encephalopathy;Computer Analysis;contact sports;Craniocerebral Trauma;CTSB gene;Data;Deposition;Development;Diagnosis;Diagnostic;diagnostic biomarker;Disease;Disease Pathway;Exposure to;frontal lobe;Frontotemporal Dementia;Functional disorder;Future;Gene Expression;Genes;Genetic;Genetic Carriers;Genetic Risk;genetic risk factor;genetic signature;Genetic Transcription;Genomics;Goals;head impact;Human;hyperphosphorylated tau;Imaging Techniques;Immunofluorescence Immunologic;Impairment;Individual;Inflammation;Knowledge;Label;Lesion;Link;Lipofuscin;lysosomal proteins;Lysosomes;Measures;Mediating;Microglia;Microscopy;Military Personnel;military service;Mission;Morbidity - disease rate;mortality;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;neuropathology;novel;novel diagnostics;novel marker;novel therapeutic intervention;novel therapeutics;Pathogenesis;Pathology;PECAM1 gene;Peptide Hydrolases;Phagocytosis;Populations at Risk;Positioning Attribute;pre-doctoral;Predisposition;Process;Proteins;Public Health;quantitative imaging;repository;Research;Risk;risk variant;Role;Severities;Shapes;Single Nucleotide Polymorphism;single nucleus RNA-sequencing;Statistical Models;Stress;Structure;tau Proteins;tau-1;Tauopathies;Techniques;Therapeutic;Therapeutically Targetable;Tissues;Training;Transcript;transcriptomics;United States National Institutes of Health;Work

PROJECT_TITLE: Microglial Lysosomal Dysfunction Following Head Trauma Contributes to Tau Pathology in Chronic Traumatic Encephalopathy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F01A-V(20)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes

ORG_CITY: Nashville

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE As one of the leading causes of death world-wide, diabetes cases are steadily rising each year contributing to an increasing concern and need to understand the mechanisms of diabetes disease progression. This study aims to unravel the mechanisms of arginine transport that contribute to pancreatic islet α-cell proliferation and glucagon secretion which contributes to hyperglycemia in diabetes. In addition to possibly identifying new targets to combat diabetes, support from this diversity fellowship will provide invaluable training to support my development as a future independent diabetes research scientist.

PI_NAMEs: STANLEY, JADE ELISE (contact)

PROGRAM_OFFICER_NAME: BODDIE, THOMAS ARTIS

PROJECT_TERMS: Affect;Alpha Cell;Amino Acid Transporter;Amino Acids;arginase;Arginine;Basic Amino Acid Transport Systems;Blood;blood glucose regulation;Calcium;calcium indicator;career;Cations;Cause of Death;Cell Physiology;Cell Proliferation;Cell secretion;Cells;Chemicals;Clinical Trials;Co-Immunoprecipitations;combat;CRISPR/Cas technology;Data;Development;Diabetes Mellitus;Disease Progression;Endocrine;Environment;Enzyme Inhibition;experimental study;Failure;Feedback;Fellowship;FRAP1 gene;Functional disorder;Future;Glucagon;Gluconeogenesis;Glucose;Glutamine;Hormone secretion;Human;hyperglucagonemia;Hyperglycemia;Hyperplasia;Image;Immunohistochemistry;Impairment;in vivo Model;Incubated;Individual;Insulin;insulin secretion;Insulin-Dependent Diabetes Mellitus;Interruption;islet;Islets of Langerhans;Knock-out;Knockout Mice;Liver;Measures;Membrane;Mentors;Mentorship;Metabolism;Modeling;Modification;Molecular;Monitor;mouse model;Mus;new therapeutic target;Nitric Oxide;Nitric Oxide Pathway;Non-Insulin-Dependent Diabetes Mellitus;Nutrient;Pathway interactions;Physiological;Production;Proliferating;Property;protein protein interaction;Proteins;Qualifying;Regulation;Research;Resources;Rodent Model;Role;Scientist;sensor;Signal Transduction;small molecule;Structure of alpha Cell of islet;Structure of beta Cell of islet;System;Testing;Therapeutic;Tissues;tool;Training;Transgenic Mice;Western Blotting;Work

PROJECT_TITLE: The Role of Arginine Transport on Pancreatic Alpha Cell Proliferation and Function


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

ORG_STATE: NY

PHR: Project Narrative  The primary site of prostate cancer metastasis is bone, which is associated with significant morbidity and mortality. Our studies employ novel in vivo models and molecular approaches to elucidate tumor cell intrinsic and tumor cell extrinsic mechanisms underlying bone metastasis. Our studies aimed at understanding the molecular causes of bone metastasis may provide new insights for early detection and new opportunities for treatment that may ultimately improve the outcome of patients with bone metastasis.

PI_NAMEs: ABATE-SHEN, CORY  (contact)

PROJECT_TERMS: 3-Dimensional;Address;Affect;Allografting;Androgens;Biological;Biological Assay;bone;Bromodomain;Cancer Etiology;candidate identification;candidate validation;Cells;Cellular Structures;Cessation of life;Coculture Techniques;cofactor;Collaborations;Complement;CRISPR screen;Data;data management;deprivation;Early Diagnosis;EP300 gene;Evolution;Foundations;Genetic Complementation Test;Genetically Engineered Mouse;genome-wide;Habitats;Human;Immune;immunodeficiency;improved outcome;In Vitro;in vivo;in vivo Model;insight;Investigation;LoxP-flanked allele;Malignant neoplasm of prostate;member;men;Metastatic Neoplasm to the Bone;Metastatic Prostate Cancer;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;neuroendocrine differentiation;novel;organ on a chip;Pathway interactions;Patient-Focused Outcomes;Population;Primary Neoplasm;Process;prostate cancer metastasis;prostate carcinogenesis;Proteins;Regulation;Research;Role;Signal Transduction;single cell sequencing;Site;Specific qualifier value;Specificity;transcription factor;Tropism;tumor microenvironment;tumor progression;Tumor-associated macrophages;Validation;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Project 2: Investigating cell intrinsic and extrinsic drivers of prostate cancer bone metastasis


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Building Research Capacity at Institutions with Limited NIH Funding;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Women's Health Research

ORG_CITY: LAS VEGAS

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF NEVADA LAS VEGAS

ORG_STATE: NV

PHR: Project narrative Public health relevance: Clostridium difficile infection (CDI) is a deadly hospital-borne infection. In both humans and mice, females are more susceptible to CDI than males. The goal of this proposal is to test the effect of estrus cycle and sex hormone levels on CDI onset and severity.

PI_NAMEs: ABEL-SANTOS, ERNESTO V (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Affect;Animals;Antibiotics;Bacterial Infections;Biological;Biological Process;Biomedical Research;biosignature;Blood;Body Temperature;Cells;Cessation of life;chemotherapy;Clostridium difficile;cohort;Colitis;Colon;Contracts;cost;cost estimate;Data;Data Analyses;Death Rate;Diagnosis;Diarrhea;Estradiol;Estrous Cycle;Estrus;experimental group;Female;follow-up;Germination;Goals;Gonadal Steroid Hormones;graduate student;Grant;gut microbiota;Health;Health Care Costs;Healthcare Systems;high risk;high risk men;Hormonal;Hormonal Change;Hormones;Hospitals;Human;Immune system;Immunity;immunological status;Immunologics;Incidence;Individual;individual patient;Infection;Infection prevention;infection risk;Inflammation;Intestines;Investigation;Knowledge;male;Male Castration;men;Metronidazole;microbiota;Modeling;Molecular;Monitor;mouse model;Multicenter Studies;Mus;Nosocomial Infections;novel strategies;Older Population;Organ Transplantation;Outcome;Ovariectomy;Patient Recruitments;Patient-Focused Outcomes;Patients;Phase;Population;Predisposition;Progesterone;prophylactic;Prophylactic treatment;public health relevance;Relapse;Reporting;Reproduction spores;Research Personnel;response;Risk Factors;screening;Serum;Severities;sex;Sex Bias;sex variable;sexual dimorphism;symptomatology;Symptoms;targeted treatment;Testing;Time;Tissues;Toxin;Training;Treatment Failure;undergraduate student;Vancomycin;Virulence;Woman;Work

PROJECT_TITLE: Effects of estrus cycle stages on murine CDI severity


PHR: Project Narrative  Our proposed studies are highly significant at the translational level since neuroendocrine differentiation represents a common mechanism of treatment resistance for castration-resistant prostate cancer. We will pursue a comprehensive analysis of neuroendocrine differentiation in both development and cancer to provide a unique perspective for delineating the molecular mechanisms of treatment-induced transdifferentiation in prostate tumors. Our analyses should identify molecular targets that are specific for neuroendocrine prostate cancer, which can be utilized to block the emergence of this highly lethal disease.

PROJECT_TERMS: Abate;Address;Androgen Antagonists;androgen independent prostate cancer;Androgen Receptor;Androgens;Bioinformatics;Biological Assay;Candidate Disease Gene;candidate identification;cell type;Cells;Clinical;Collaborations;comparative;Comparative Study;Computer Analysis;Data;data management;deprivation;Development;Disease;effective therapy;Environment;Epithelium;FGFR1 gene;Generations;Genetic Complementation Test;Genetically Engineered Mouse;Heterogeneity;Human;human tissue;in vivo;innovation;interest;Intrinsic factor;Investigation;Ligands;Malignant neoplasm of prostate;Malignant Neoplasms;Mesenchyme;Modeling;Molecular;Molecular Analysis;Molecular Target;mouse model;multiplexed imaging;Mus;NCAM1 gene;neoplastic cell;Neuroendocrine Cell;neuroendocrine differentiation;neuroendocrine phenotype;Neuroendocrine Prostate Cancer;Neurosecretory Systems;novel;Organogenesis;Organoids;Pathway interactions;Pattern;prepuberty;Primary Neoplasm;programs;Prostate;prostate cancer cell;Prostatic Neoplasms;receptor;Receptor Inhibition;response;Role;Sampling;Signal Transduction;single cell ATAC-seq;single-cell RNA sequencing;Specific qualifier value;synergism;System;therapeutic target;therapy resistant;Tissue Recombination;Tissue Sample;Tissues;transcription factor;transdifferentiation;translational impact;tumor;tumor microenvironment;tumorigenic;Validation;Visualization;WNT Signaling Pathway;Work

PROJECT_TITLE: Project 3: Analysis of intrinsic and extrinsic factors that promote prostate neuroendocrine differentiation


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Eating Disorders;Genetic Testing;Genetics;Mental Health;Nutrition;Obesity;Patient Safety;Pediatric;Precision Medicine;Prevention

ORG_CITY: MINNEAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PROJECT NARRATIVE While obesity pharmacotherapies are promising adjuncts to lifestyle modification therapy for the treatment of pediatric severe obesity (defined as body mass index ≥1.2 times the 95th percentile or BMI ≥35 kg/m2; the fasting growing obesity category), there is substantial variability in their individual-level effectiveness. This proposal will assess person-specific characteristics associated with weight loss response to and affecting dosing of obesity pharmacotherapies using techniques that can be employed in precision medicine approaches: electronic health record-enabled clinical discovery, genetic risk scores (estimates of genetic propensity), and pharmacometrics (studies of drug dose-exposure-response relationships). We will apply these techniques to topiramate as an example pharmacotherapy given this medication’s ubiquity of use and significant variability in individual-level effectiveness in youth with severe obesity.

PI_NAMEs: BOMBERG, ERIC MORRIS (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: Adult;Affect;Age;Agonist;Applied Genetics;bariatric surgery;Basic Science;Behavioral;Binge Eating;Body mass index;Body Weight decreased;carbonate dehydratase;Cardiovascular Diseases;Categories;Characteristics;Childhood;Clinical;clinical care;clinical decision-making;Clinical Research;clinically significant;Data;design;Desire for food;DNA;Dopamine;Dose;dose individualization;Drug Kinetics;Drug Prescriptions;Eating Behavior;Effectiveness;Electronic Health Record;Extramural Activities;Fasting;FDA approved;Female;food craving;Funding;Future;gamma-Aminobutyric Acid;Genes;Genetic;Genetic Predisposition to Disease;Genetic Risk;GLP-I receptor;Glucagon;glucagon-like peptide 1;Glucose;Glutamates;Goals;Health;high body mass index;improved;improved outcome;increased appetite;Individual;individual variation;Infrastructure;inhibitor;Intervention;K-Series Research Career Programs;Life Style Modification;Medicine;Mentorship;Metabolic;Methods;Morbid Obesity;multidisciplinary;Non-Insulin-Dependent Diabetes Mellitus;obese patients;Obesity;obesity in children;obesity management;obesity risk;obesity treatment;Outcome;Participant;Pathway interactions;patient population;Patients;Persons;Pharmaceutical Preparations;pharmacodynamic model;Pharmacogenomics;pharmacokinetics and pharmacodynamics;Pharmacological Treatment;pharmacometrics;Pharmacotherapy;Phenotype;Physicians;Play;Population;precision medicine;predicting response;Predictive Factor;Prospective, cohort study;recruit;Regimen;Research;Research Personnel;response;Retrospective cohort study;Risk;risk minimization;risk selection;Role;Scientist;Seizures;sex;Single Nucleotide Polymorphism;skills;Sodium;Specialist;surgical risk;symporter;Techniques;Therapeutic;topiramate;Training;Training Programs;United States National Institutes of Health;Youth

PROJECT_TITLE: Precision Medicine Approaches to Obesity Pharmacotherapy in Youth with Severe Obesity

STUDY_SECTION: DDK

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