ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: Research Triangle Park

ORG_NAME: EPICYPHER, INC.

PHR: PROJECT NARRATIVE  Gene expression is regulated by the integration of DNA methylation (DNAme) and other chromatin features, including chromatin accessibility, histone post-translational modifications (PTMs), chromatin remodelers, and transcription factor binding. However, our understanding of how DNAme co-occurs (and coordinates) with these features to control gene expression is limited by a lack of reliable genomic tools. Here, EpiCypher is partnering with New England Biolabs (NEB) to develop an ultra-sensitive multiomic mapping technology that delivers high resolution DNAme (5mC/5hmC) profiles at defined chromatin features, providing a powerful new approach to advance our understanding of chromatin regulation and unlock the full potential of epigenetic-targeting therapeutics and diagnostics.

PI_NAMEs: KEOGH, MICHAEL-CHRISTOPHER  (contact);VENTERS, BRYAN J

PROGRAM_OFFICER_NAME: MORRIS, STEPHANIE A

PROJECT_TERMS: Acceleration;Acetylation;Adoption;Antibodies;Bar Codes;Benchmarking;Binding;Bioinformatics;Biological Assay;Biological Markers;Biological Sciences;bisulfite;bisulfite sequencing;Cell Line;Cells;Chemicals;Chromatin;chromatin immunoprecipitation;Cleavage Under Targets and Release Using Nuclease;Clinical;clinical application;Complex;Data;data and analysis portal;Development;Diagnostic;Disease;DNA;DNA analysis;DNA Integration;DNA Methylation;DNA methylation profiling;Dose;Drug Targeting;Epigenetic Process;Epitopes;Exhibits;experimental study;Freezing;Gene Expression;genomic tools;Genomics;high throughput screening;Histones;human embryonic stem cell;inhibitor;innovation;K-562;laboratory development;Letters;Lysine;Malignant Neoplasms;Manuals;Maps;MCF7 cell;Methods;Methylation;methylation pattern;Molecular;Monitor;multiple omics;Nervous System Disorder;New England;next generation;Noise;novel;novel strategies;Nucleosomes;Pharmacotherapy;Phase;Post-Translational Protein Processing;Proteins;Protocols documentation;Regulation;Resolution;response;Sampling;Savings;Services;Signal Transduction;targeted treatment;Technology;Time;Tissues;Titrations;tool;transcription factor;Ubiquitination;user-friendly

PROJECT_TITLE: Ultrasensitive multiomic platform using epitope-targeted DNA methylation mapping


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Social Determinants of Health

ORG_CITY: ALBUQUERQUE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: SOCIAL SCIENCES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF NEW MEXICO

ORG_STATE: NM

PHR: PROJECT NARRATIVE Aging is a process that is shaped by experiences across the life course, such as social inequality and social support, yet the ability to quantify individual experience over the long human lifespan remains a hindrance to aging research. Chimpanzees, a long-lived species with close genetic and physiological similarities to humans, offer a tractable way to approach life course studies due, in part, to decades of detailed, objective observations conducted on the two longest-studied populations in Africa. Building on an initial study that developed and validated non-invasive measures of health and aging in wild chimpanzees, these aims will investigate the cumulative influences of infection and social processes on health and mortality outcomes.

PI_NAMEs: GILBY, IAN ;GOLDBERG, TONY L.;LONSDORF, ELIZABETH VINSON;ROSATI, ALEXANDRA G;THOMPSON, MELISSA EMERY (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Accreditation;Address;Adult;Africa;African;Age;age difference;age related;Age related pathologies;aged;Aging;aging process;biobank;Biological;Biological Markers;Biological Models;Biology of Aging;Blood;Caring;Chronic;Clinical;Collaborations;Communities;comparative;Complex;Costs and Benefits;Data;data access;data mining;Data Set;Databases;Dimensions;Disease;Education;emerging adult;Environment;Environmental Exposure;Environmental Risk Factor;Evolution;experience;Exposure to;Feces;Feedback;Female;Funding;Genetic;Health;health data;health disparity;health inequalities;Health Status;Health Surveys;healthy aging;high dimensionality;Human;Human Biology;human disease;human model;Immune system;immunosenescence;Individual;individual variation;Infection;infection burden;Inflammation;interest;Intervention;Laboratories;Laboratory Animal Models;late life;Life;Life Cycle Stages;life span;Life Style;lifestyle factors;Link;Longitudinal Studies;male;Measures;Mediating;Medical;Methods;Modeling;Monitor;mortality;Nature;normal aging;novel;Older Population;Outcome;Oxidative Stress;Pan Genus;Parasitic infection;Pattern;Phase;Physical environment;Physiological;Physiology;Play;Population;Primates;Process;Recording of previous events;Research;Resources;Role;Sampling;senescence;Shapes;Smoking;social;social attachment;Social Behavior;social disparities;Social Environment;social influence;social integration;Social Interaction;Social Network;social observations;Social Processes;Social status;Social support;social vulnerability;Stress;stressor;study population;success;System;Tanzania;Testing;theories;Time;Translating;Uganda;urinary;Urine;virtual;Virus Diseases

PROJECT_TITLE: Cumulative Life Course Effects on Aging and Health in a Long-Lived Primate Model

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Disability Research;Health Services;Neurodegenerative;Neurosciences;Palliative Care;Social Determinants of Health

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Project Narrative This is a mid-career mentoring award that will expand Dr. Smith’s time and ability to mentor clinician- researchers in patient-oriented aging research and conduct research on meaningful activities among persons with Alzheimer’s disease and related dementias.

PI_NAMEs: SMITH, ALEXANDER KELIIMOEANU (contact)

PROJECT_TERMS: Acceleration;Address;Admission activity;Aging;Alzheimer's disease related dementia;Area;Award;Behavioral Research;Bioethics;Books;career;career development;Caring;Cessation of life;Cognition;Cognitive;Collaborations;cost comparison;Data;Data Set;Decision Making;Dementia;design;disability;experience;Faculty;Family;Geriatrics;Gerontology;Goals;Health;Health Care Costs;Human;improved;Intervention;Investments;Journals;Knowledge;Laboratories;leadership development;Link;Measures;Medical;Medicare;Medicare claim;Mentors;mortality;Nursing Homes;older adult;online resource;Outcome;Outcome Measure;Palliative Care;patient oriented;patient oriented research;Peer Review;Personal Satisfaction;Persons;podcast;Policies;Predictive Factor;Prognosis;prognostic index;prognostic model;Publications;Quality of life;Reading;recruit;Religion;Research;Research Personnel;Research Project Grants;Research Support;Resources;Risk;Self Care;Services;Shapes;social;social factors;Social isolation;Social support;Soil;Time;trend;Well in self;Work

PROJECT_TITLE: Meaningful Activities and Alzheimer's Disease and Related Dementias

STUDY_SECTION: NIA

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: HOUGHTON

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: MICHIGAN TECHNOLOGICAL UNIVERSITY

ORG_STATE: MI

PHR: NARRATIVE Salt sensitive hypertension (SSH) is responsible for 51% of all cases of hypertension in the United States, and is a major risk factor for development of cardiovascular disease with serious social and economic impacts. Our preliminary data suggests that abnormal orexin signaling in the paraventricular nucleus (PVN), a major cardiovascular control brain region, may increase sympathetic outflow and upregulate hypothalamic-pituitary- adrenal (HPA) axis following a high salt intake, resulting in the development of SSH. Our study proposes to investigate the role and mechanism of orexin signaling in the development of SSH by means of genetic knockdown or chronic overexpression of the PVN orexin receptor combined with electrophysiological recording, as well as molecular and immunohistochemical approaches to further elucidate the signaling pathways that lead to excitatory neurochemical release, inflammation, and subsequent increased SNA outflow and dysregulated HPA axis.

PI_NAMEs: SHAN, ZHIYING  (contact)

PROGRAM_OFFICER_NAME: OH, YOUNGSUK

PROJECT_TERMS: Accounting;Adrenal Glands;Animal Model;antagonist;Area;Arousal;Attenuated;Binding;Biochemical;Blood Pressure;blood pressure reduction;blood pressure regulation;Brain;brain control;Brain region;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Physiology;cardiovascular risk factor;Cardiovascular system;Cause of Death;Cells;Central Nervous System;Chronic;combat;Corticosterone;Corticotropin;Corticotropin-Releasing Hormone;cytokine;Cytokine Signaling;Data;Development;Disease;economic impact;Electrophysiology (science);Etiology;Extracellular Signal Regulated Kinases;feeding;Gene Expression;Genetic;Genetic Transcription;Growth;high salt diet;hormonal signals;Hormones;Human;human model;Hyperactivity;Hypertension;hypertension treatment;hypertensive;hypocretin;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;Impairment;in vivo;Inbred Dahl Rats;Inbred SHR Rats;Inflammation;Inflammatory;Injections;Intake;knock-down;Lateral;Lesion;Maintenance;MAPK3 gene;Mediating;Modeling;Molecular;mRNA Expression;Nerve;neurochemistry;Neuroendocrine Cell;Neurons;Neuropeptides;Neurosecretory Systems;neurotransmission;new therapeutic target;normotensive;Obesity;orexin 1 receptor;orexin A;orexin B;Outcome;overexpression;paraventricular nucleus;Phosphorylation;Physiological;Pituitary Gland;Plasma;Play;prevent;Production;Rattus;receptor;Receptor Activation;receptor expression;Receptor Signaling;Regulation;Resistance;response;Rewards;Risk Factors;Role;Saline;salt intake;salt sensitive;salt sensitive hypertension;Signal Induction;Signal Pathway;Signal Transduction;Social Impacts;Sodium Chloride;Sprague-Dawley Rats;Stress;System;Testing;Therapeutic Intervention;TNF gene;Transduction Gene;United States;Up-Regulation;Vasopressins;Zucker Rats

PROJECT_TITLE: Contribution of Orexin System to Hypertension

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Women's Health Research

ORG_CITY: ROCHESTER

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Project Narrative The inability to successfully block metastatic spread remains a significant barrier to long-term cancer survival. A key early step in the progression to metastatic disease is an increase in cell state plasticity that allows some cancer cells to adapt to new environments and take on new migratory and invasive capabilities. This flexibility involves changes in non-permanent, but relatively stable chemical modifications to the DNA packaging material and a loss of control over which genes are expressed and by how much. Our studies will determine how such epigenetic modifications cross-talk to the transcriptional machinery to enforce cell state stability and suppress breast cancer cell invasion, providing new potential avenues for therapeutic intervention.

PI_NAMEs: VERTINO, PAULA M. (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: 3-Dimensional;Acetylation;Automobile Driving;Behavior;Binding;Biological Assay;Breast;Breast Cancer Cell;Breast Epithelial Cells;cancer cell;cancer survival;Cell Maintenance;Cells;Characteristics;chemical stability;Chemoresistance;Chromatin;Complex;Deposition;Development;Diagnosis;Disease;Distant Metastasis;DNA Packaging;DNA-Directed RNA Polymerase;Down-Regulation;Environment;epigenetic memory;Epigenetic Process;epigenetic variation;epigenome;epigenome editing;epithelial to mesenchymal transition;Epithelium;Exhibits;flexibility;Gene Expression;Genes;Genetic Transcription;genome-wide;Goals;Heterogeneity;Histone H4;histone methyltransferase;Hybrids;insight;Invaded;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Mesenchymal;Metastatic breast cancer;Methylation;Modeling;Modification;Molecular;mortality;neoplastic cell;novel;packaging material;Patients;Phenotype;Play;Polymerase;posttranscriptional;Precision Run-On Sequencing;Primary Neoplasm;Process;programs;promoter;Property;Reader;recruit;Regulation;Relaxation;Repression;Residual state;response;RNA;RNA Polymerase II;Role;Site;Small Nuclear Ribonucleoproteins;Solid Neoplasm;Source;spheroids;stem;stemness;Tail;Technology;Testing;Therapeutic Intervention;transcription factor;Transcriptional Regulation;transcriptional reprogramming;Transforming Growth Factor beta;triple-negative invasive breast carcinoma;Variant;Woman;women's diagnosis

PROJECT_TITLE: Relaxed Polymerase Pausing as a Driver of Epigenetic Plasticity and Cancer Cell Invasion

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


NIH_SPENDING_CATS: Behavioral and Social Science;Burden of Illness;Cancer;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Palliative Care;Patient Safety;Prevention;Social Determinants of Health

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: Project Narrative The proposed study directly addresses recommendations from the National Cancer Institute (NCI) and American Society of Clinical Oncology (ASCO) to urgently design and test interventions to decrease financial toxicity in cancer care. This proposal offers a proactive financial navigation program, one of the first large-scale interventions to address financial toxicity, and goes beyond evaluating financial outcomes to look at health and social outcomes in cancer patients and their spouse caregivers. Findings from this study will address the role of financial navigation in mitigating household financial hardship and its psychosocial and medical consequences and could support the inclusion of financial navigation as an essential component of high-quality cancer care.

PI_NAMEs: SHANKARAN, VEENA  (contact)

PROGRAM_OFFICER_NAME: CASTRO, KATHLEEN M

PROJECT_TERMS: Address;Advocate;Affect;American Society of Clinical Oncology;arm;Bankruptcy;Behavior Therapy;Behavioral;Budgets;cancer care;cancer diagnosis;Cancer Patient;care delivery;Caregiver Burden;Caregiver well-being;Caregivers;caregiving;Caring;Case Manager;Clinic;Clinical;Collaborations;Collection;Community Clinical Oncology Program;community organizations;copayment;cost;Counseling;Couples;Data;Data Reporting;design;Development;Diagnosis;Disease;Disparity;Education;Emergency department visit;end of life;Enrollment;evidence base;exhaust;experience;Facilities and Administrative Costs;Family;Family Study;Financial Hardship;financial literacy;Financial Support;financial toxicity;Foundations;Goals;Health;Health Care Costs;health care service utilization;health disparity;Healthcare;high risk;Hospitalization;Hospitals;Household;Improve Access;improved;Incidence;Income;Insurance;Intervention;intervention effect;Judgment;Link;Low income;Low Income Population;Malignant Neoplasms;Medical;Medical Care Costs;Medical Records;medication nonadherence;National Cancer Institute;novel;Oncology;Outcome;Outcome Assessment;Outcome Study;Participant;patient navigation;Patients;payment;Pharmaceutical Preparations;pilot test;pragmatic randomized trial;primary endpoint;primary outcome;Professional counselor;programs;prospective;psychologic;psychosocial;Psychosocial Assessment and Care;Quality of life;racial minority;Randomized;Recommendation;remote administration;Reporting;Research;Resources;response;Risk;Role;Services;side effect;Social outcome;Socioeconomic Status;Spouse Caregiver;Spouses;Standardization;Subgroup;Surveys;Testing;Training;Training and Education;treatment arm;treatment as usual;Uninsured Medical Expense;United States;Work

PROJECT_TITLE: Addressing Cancer-Related Financial Hardship through Delivery of a Proactive Financial Navigation Intervention

STUDY_SECTION: HSOD

STUDY_SECTION_NAME: Health Services Organization and Delivery Study Section[HSOD]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Pancreatic Cancer;Rare Diseases

ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: PROJECT NARRATIVE Pancreatic ductal adenocarcinoma (PDA) is a highly aggressive cancer that up-regulates autophagy and lysosomes – acidic organelles where autophagic cargo is degraded – to maintain growth. We have identified a new role for the autophagy-lysosome pathway in targeting the major histocompatibility complex class I (MHC-I) protein for degradation as a mechanism of immune evasion. Our proposal will determine the underlying molecular mechanisms responsible for MHC-I dysregulation, with the ultimate goal of identifying new nodes that can be targeted to restore MHC-I on the surface of PDA cells and enhance immune cell mediated tumor killing.

PI_NAMEs: PERERA, RUSHIKA MIRIAM (contact)

PROGRAM_OFFICER_NAME: SALNIKOW, KONSTANTIN

PROJECT_TERMS: Address;Affinity;Antigen Presentation;Autophagocytosis;Autophagosome;Binding;Biochemistry;Biogenesis;BRCA1 gene;cancer cell;Cell Line;Cell membrane;Cell surface;Cells;Complex;Coupled;Endoplasmic Reticulum;Endowment;Ensure;Epithelium;Evolution;Excision;fitness;Genetic;genetic approach;Goals;Golgi Apparatus;Grant;Growth;Human;Immune;immune checkpoint blockade;Immune Evasion;Immunofluorescence Immunologic;immunogenicity;In Vitro;in vivo;Location;Lysosomes;Major Histocompatibility Complex;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;metabolic fitness;Molecular;mouse model;Mus;Neoplasm Metastasis;Normal Cell;novel;Organelles;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;Pancreatic Intraepithelial Neoplasia;Pathway interactions;Patients;peptide I;Peptides;Post-Translational Protein Processing;protein degradation;Proteins;Proteomics;Publications;receptor;Recycling;Role;Route;Sampling;Specimen;Stains;Surface;System;T-Lymphocyte;Testing;Tissue Banks;trafficking;tumor;Tumor Tissue;Ubiquitin;ubiquitin ligase;Work

PROJECT_TITLE: Targeting the autophagy-lysosome system to block pancreatic cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Cannabinoid Research;Clinical Research;Drug Abuse (NIDA only);Pediatric;Prevention;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Legalization of cannabis use for adults has the potential to increase rates of cannabis, alcohol, and tobacco use among teens, young adults, and parents, all of which are serious public health problems associated with significant morbidity, mortality and poor functioning. Guided by theory that has proven useful in disentangling multiple influences on these behaviors, this project will provide information vital to preventing underage and problematic cannabis use and preventing increases in alcohol and cigarette use in the context of legalized cannabis use.

PI_NAMEs: BAILEY, JENNIFER A (contact)

PROGRAM_OFFICER_NAME: KIMMEL, HEATHER L

PROJECT_TERMS: Acceleration;Address;Adolescent;adolescent offspring;Adult;Adult Children;Affect;Age;Alcohol consumption;alcohol measurement;Alcohols;Attention;Behavior;Binding;Biological;Birth;Cannabis;Cannabis retail;cannabis use behavior;Caregivers;Child;cigarette smoking;cohort;Communities;Cross-Sectional Studies;Data;Data Collection;Development;Developmental Course;Drug usage;evidence base;Family;Frequencies;Funding;Goals;Individual;intergenerational;Knowledge;Legal;Life Cycle Stages;Link;longitudinal design;Longitudinal Studies;marijuana legalization;marijuana use;Measures;Methods;Modeling;Morbidity - disease rate;mortality;Nicotine;nicotine use;offspring;Outcome;Parents;Pattern;peer;Persons;Policies;Prevalence;prevent;Prevention;Probability;prospective;psychosocial;Public Health;Recreation;Research;Risk Factors;Short Waves;Social Development;Spouses;Stretching;substance use;Teenagers;theories;Time;Tobacco use;virtual;Washington;Work;young adult;Youth

PROJECT_TITLE: Cannabis Legalization a Decade Later: A Longitudinal Study of Teens, Young Adults, and Parents in Washington State

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


PHR: PROJECT NARRATIVE Advanced non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide with limited treatment options. This proposal utilizes biochemical and immunological techniques to investigate the mechanism of a novel pathway that induces tumor regression in NSCLC. The findings from this study will have a direct impact on the development of new therapeutic strategies for patients with this deadly disease.

PI_NAMEs: WANG, VICTORIA  (contact)

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Ablation;Accounting;Advisory Committees;Affinity;Alleles;Apoptosis;Apoptotic;Area;autocrine;Binding;Biochemical;Biology;Biometry;BRAF gene;Cancer Biology;Cancer cell line;Cancer Etiology;Cancer Patient;cancer regression;career;career development;CD8-Positive T-Lymphocytes;Cell model;Cells;Cessation of life;Clinical;Clinical Trials;Collaborations;Combined Modality Therapy;cytokine;Data;Data Reporting;Databases;derepression;Development;Disease;Drug Targeting;Environment;experience;Family member;Feedback;FGF1 gene;Funding;Genetic;Genetically Engineered Mouse;Goals;Growth Factor;Guanosine Triphosphate;Human;Immune;Immunologic Techniques;Immunologics;Immunology;improved;Individual;Induction of Apoptosis;inhibitor;innovation;insight;Institution;knock-down;KRAS2 gene;laboratory experience;Literature;Lung Neoplasms;lung tumorigenesis;Malignant neoplasm of lung;Malignant Neoplasms;MAP Kinase Gene;Mass Spectrum Analysis;Mediating;meetings;Mentors;Mentorship;Modeling;Molecular;mortality;mutant;Mutation;Non-Small-Cell Lung Carcinoma;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Oncogenic;Operative Surgical Procedures;Pathway interactions;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;PIK3CG gene;potential biomarker;predicting response;Principal Investigator;Production;programs;Proteins;Proteomics;Publishing;RAF1 gene;rational design;Reporting;Research;Research Personnel;Resected;resistance mechanism;Resources;Secondary to;Sequence Alignment;Signal Transduction;System;systemic toxicity;T cell infiltration;T-Lymphocyte;Technical Expertise;Testing;The Cancer Genome Atlas;Training;transcriptome sequencing;translational cancer research;Translational Research;tumor;Tumor Cell Line;tumor growth;tumor microenvironment;United States;United States National Institutes of Health;Work

PROJECT_TITLE: Mechanistic Determination of KRAS Lung Cancer Regression upon CRAF Suppression

STUDY_SECTION: NCI

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


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Cancer;Hematology;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE  The PLC-gamma isozymes are important clinical targets for the treatment of various cancers, yet, there are no efficacious and selective inhibitors of the PLC-gamma isozymes that can be used as leads for drug development. We propose to develop and implement a high-throughput platform to identify efficacious and selective inhibitors of the PLC-gamma isozymes. These compounds will be essential as chemical probes to dissect cellular functions of PLC- gamma isozymes and will also serve as leads for the development of drugs to treat human diseases promoted by aberrantly active PLC-gamma isozymes.

PI_NAMEs: PEARCE, KENNETH HUGH;SONDEK, JOHN E;ZHANG, QISHENG  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Active Sites;Adult T-Cell Leukemia/Lymphoma;Allosteric Regulation;analog;B-Cell Leukemia;B-Lymphocytes;Binding;Biochemical;Biological Assay;Biophysics;Catalytic Domain;Cell Physiology;Cellular Assay;Cellular biology;Chemicals;Chemotaxis;Clinical;Collection;Combination Drug Therapy;Cutaneous T-cell lymphoma;design;Development;Diglycerides;Disease;drug development;drug-like compound;Etiology;extracellular;Fluorescence;Genetic;Genetic Transcription;Goals;Growth Factor;Hemangiosarcoma;Hematologic Neoplasms;high throughput screening;Hormones;Human;human disease;Immune System Diseases;Immunologic Receptors;Inflammatory;Informatics;inhibitor;inorganic phosphate;Inositol;Isoenzymes;Length;leukemia/lymphoma;Ligands;Malignant Neoplasms;Mediating;Membrane;migration;Modeling;Monitor;Mutate;Mutation;Nerve;Neurotransmitters;NF-kappa B;novel;nuclear factors of activated T-cells;Patients;Peripheral;personalized medicine;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Phospholipase;Phospholipase C;phospholipase C gamma;phospholipase inhibitor;Phospholipids;Phosphorylation;PLC gamma1;PLCgamma2;Proliferating;Protein Isoforms;Protein Kinase C;Proteins;Receptor Protein-Tyrosine Kinases;Recurrent disease;Refractory Disease;Regulation;Resolution;response;Role;Second Messenger Systems;Signal Transduction;Signaling Protein;small molecule inhibitor;standard of care;Stimulus;Structure;success;T-Cell Lymphoma;T-Cell Receptor;T-Lymphocyte;Therapeutic;Therapeutic Agents;therapeutic development;therapeutic target;Time;tool;Toxic effect;treatment response

PROJECT_TITLE: A high-throughput platform to identify selective allosteric inhibitors of the PLC-y isozymes

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Bioengineering;Clinical Research;Data Science;Health Services;Kidney Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention

PHR: PROJECT NARRATIVE Early recognition of chronic kidney disease (CKD) delays progression to kidney failure. However, preterm born children, who are high risk for kidney disease, are not routinely screened for CKD and often do not experience symptoms until the kidney damage is severe and irreversible leading to a 4-fold increase in healthcare costs. This project aims to develop a clinical risk stratification tool to help clinicians identify preterm born infants at the highest risk for kidney disease in early life to support quality screening practices and early interventions to reduce progression of CKD, improve health outcomes, and reduce health care costs.

PI_NAMEs: SANDERSON, KEIA  (contact)

PROGRAM_OFFICER_NAME: GREER, RAQUEL CHARLES

PROJECT_TERMS: Adolescent;Albumins;Albuminuria;Angiotensin-Converting Enzyme Inhibitors;Award;Biological Markers;Birth;Blood Pressure;blood pressure elevation;career development;Cessation of life;Child;Child Care;Child Health;Child Support;Childhood;Chronic Kidney Failure;Clinical;clinical decision support;clinical risk;Clinical Sciences;cohort;Collaborations;Complex;connected health;Creatinine;Data;Data Science;Databases;Development;Disease Progression;disorder risk;Early Diagnosis;Early Intervention;early life exposure;early screening;Educational workshop;Effectiveness;effectiveness testing;Environment;Erythropoietin;experience;extreme prematurity;Extremely low gestational age newborn;Faculty;Foundations;Funding;Future;Goals;Grant;Health;health application;Health Care Costs;high risk;improved;Infant;interest;Internet;Intervention;Interview;Kidney;Kidney Diseases;kidney dysfunction;Kidney Failure;kidney preservation;Knowledge;Leadership;Life;Literature;Machine Learning;machine learning method;machine learning model;mathematical model;Medical;member;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methods;Microalbuminuria;Modeling;Monitor;Neonatal;neonatal exposure;Neonatal Intensive Care Units;neonatal outcome;nephrogenesis;Nephrology;neuroprotection;North Carolina;Online Systems;Outcome;Outcomes Research;Participant;pediatrician;Peer Review;Perinatal;Perinatal Exposure;Pharmaceutical Preparations;Population;postnatal;practical application;predictive tools;preference;Pregnancy;premature;Premature Birth;prenatal;Preparation;Prevalence;prevent;Productivity;Prospective cohort;prototype;Publications;Qualitative Research;recruit;renal damage;Renal function;Renal Mass;Research;Research Methodology;Research Personnel;Research Project Grants;Risk;Risk Estimate;Risk Factors;Risk Marker;risk prediction;risk prediction model;risk stratification;Sampling;Science;screening;Screening procedure;Serum;Site;skill acquisition;skills;sociodemographics;Structure;support tools;Symptoms;Testing;tool;tool development;Training;Training Support;Translational Research;United States National Institutes of Health;Universities;Urine;usability;web-based assessment;web-based tool;Work;Writing

PROJECT_TITLE: Machine Learning Risk Prediction of Kidney Disease After Extremely Preterm Birth

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Kidney, Urologic and Hematologic Diseases D Study Section[DDK-D]


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Opioid Misuse and Addiction;Opioids;Pain Research;Palliative Care;Social Determinants of Health;Substance Misuse

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative: Research on the management of comorbid opioid misuse/OUD and chronic pain is being outpaced by the clinical need across populations and settings. This K24 mid-career investigator award will support the mentored career development of PhD students, post-doctoral scholars, and faculty from diverse disciplines, particularly women and individuals from backgrounds underrepresented in science, in research at the intersection of these conditions.

PI_NAMEs: MERLIN, JESSICA S (contact)

PROGRAM_OFFICER_NAME: SU, SHELLEY

PROJECT_TERMS: acceptability and feasibility;Active Learning;addiction;Address;Adopted;Adoption;Advanced Malignant Neoplasm;Alcohols;Area;Award;Behavior;Behavioral;Buprenorphine;cancer care;Cancer Pain Management;career;career development;case-based;chronic abdominal pain;chronic pain;chronic pain patient;Clinic;Clinical;clinical practice;Cocaine;comorbidity;Complication;Data;data submission;design;Development Plans;Diagnosis;Discipline;Disease Management;Disseminated Malignant Neoplasm;Doctor of Philosophy;doctoral student;Education;effectiveness outcome;effectiveness/implementation hybrid;Equity;Evaluation;evidence base;evidence based guidelines;experience;Faculty;Funding;Goals;Health;health equity;Helping to End Addiction Long-term;High Prevalence;HIV;hybrid type 2 trial;Hybrids;implementation barriers;implementation evaluation;implementation facilitators;implementation framework;implementation protocol;implementation science;implementation strategy;improved;Individual;Institution;Interview;Language;Leadership;Life;Life Experience;Maintenance;Malignant Neoplasms;Maps;medication for opioid use disorder;Mentors;Methadone;Needs Assessment;next generation;novel;Oncology;Opioid;Opioid agonist;opioid misuse;opioid overdose;opioid use disorder;Outcome;Pain;Pain management;Palliative Care;Participant;Pathway interactions;Patient Care;Patients;Perception;Performance;Personal Satisfaction;Persons;Physicians;pilot trial;Population;Postdoctoral Fellow;prescription opioid;Primary Care;Productivity;Prognosis;programs;racial disparity;Racial Equity;racial health disparity;randomized trial;Reach, Effectiveness, Adoption, Implementation, and Maintenance;recruit;Research;Research Methodology;Research Personnel;Research Project Grants;Research Proposals;research to practice;Resources;Risk;Risk Factors;Science;Scientist;Sickle Cell;skills;social stigma;Specific qualifier value;Standardization;substance use;symposium;systematic review;Testing;Tobacco use;Training;Translations;treatment optimization;treatment research;United States National Institutes of Health;Woman;Work

PROJECT_TITLE: Mentoring the next generation of researchers at the intersection of opioid use disorder and chronic pain

STUDY_SECTION: SIHH

STUDY_SECTION_NAME: Science of Implementation in Health and Healthcare Study Section[SIHH]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: RICHLAND

ORG_NAME: BATTELLE PACIFIC NORTHWEST LABORATORIES

PHR: NARRATIVE We aim to combine wheat germ cell-free protein expression platform with active microsomes of different origin to synthesize influenza virus-like particles (VLPs). These particles will undergo detailed morphological and compositional examination using electron microscopy and native mass spectrometry to understand the architecture of obtained products and to learn the mechanisms of their assembly and composition variability. We hypothesize that this approach will be suitable for a stable and streamlined generation of Influenza VLPs and will further serve as a rapid prototyping platform for influenza vaccine development.

PI_NAMEs: POWELL, SAMANTHA MALIA (contact)

PROGRAM_OFFICER_NAME: GORDON, JENNIFER L

PROJECT_TERMS: Address;Antigens;Architecture;Biomanufacturing;Biomedical Engineering;Capsid;Cell Culture Techniques;Cell-Free System;Cells;cost;Cryo-electron tomography;Cryoelectron Microscopy;density;Disease Outbreaks;Drug Delivery Systems;Electron Microscopy;Ensure;flexibility;Future;future pandemic;Generations;Germ Cells;Glycoproteins;glycosylation;Goals;Hepatitis B Virus;Heterogeneity;Heterophile Antigens;Human;immunogenic;Individual;Influenza;Influenza A virus;Influenza A Virus, H5N1 Subtype;Influenza A Virus, H7N9 Subtype;Influenza A Virus, H9N2 Subtype;influenza virus strain;influenza virus vaccine;influenzavirus;Learning;manufacture;Mass Spectrum Analysis;Microsomes;Morphology;Mutation;Negative Staining;pandemic disease;particle;Pichia;Population;Production;prophylactic;Protein Biosynthesis;protein expression;Proteins;prototype;recombinant virus;Recombinants;research and development;Resolution;response;Safety;Sampling;self assembly;structural biology;Surface;System;Technology;Testing;three dimensional structure;tomography;vaccine development;vaccine platform;Vaccine Research;Vaccines;Variant;Viral Genome;virology;Virus;Virus-like particle;Wheat

PROJECT_TITLE: Cell-free synthesis of influenza virus-like particles (VLPs) as prototyping platform for vaccine development and variant characterization

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: NARRATIVE Our Program plans to focus on a vital unmet need in idiopathic pulmonary fibrosis (IPF), understanding the etiologic and initial pathogenic events in lung fibrosis so we can prevent the development of progressive and irreversible pulmonary fibrosis. We will accomplish this through 3 highly interactive Scientific Projects, 3 Research Cores, and an Administrative Core and by focusing on the initial pathogenic mechanisms, dominant risk factors, and a two-hit model of disease pathogenesis. In aggregate, we will identify key mechanisms that are critical to initiation of the fibroproliferative process that may serve as new targets for drug development, especially in early stages of disease.

PI_NAMEs: SCHWARTZ, DAVID ALBERT (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Address;Aging;airway epithelium;alveolar epithelium;Apoptosis;Apoptosis Promoter;Biological;biological adaptation to stress;Bleomycin;Bronchioles;Cells;Cyst;Development;Disease;disease model;disorder prevention;Distal;Dominant Genetic Conditions;drug development;Early Intervention;endoplasmic reticulum stress;Enhancers;Epigenetic Process;epigenetic regulation;Epithelial Cells;epithelial injury;Epithelium;Etiology;Event;Exposure to;Fibroblasts;Fibrosis;Functional disorder;gain of function;genetic variant;Goals;Heat shock proteins;idiopathic pulmonary fibrosis;In Vitro;Individual;Inflammation;Injury;injury and repair;Intervention;Lung;lung injury;Microscopic;Modeling;Molecular;MUC5B gene;Mus;new therapeutic target;non-genetic;novel;overexpression;Pathogenesis;Pathogenicity;Pathologic;Patients;Phenotype;Physiological;post-COVID-19;Predisposition;prevent;preventive intervention;Process;programs;promoter;Public Health;Pulmonary Fibrosis;recruit;Reporting;Research;respiratory;response;Risk;Risk Factors;Role;Scanning;Stress;Structure of parenchyma of lung;Tobacco smoke;Usual Interstitial Pneumonia;Variant

PROJECT_TITLE: Mechanisms Regulating Lung Injury and Early Lung Fibrosis

STUDY_SECTION: HLBP

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


NIH_SPENDING_CATS: Lung;Pulmonary Fibrosis

PROJECT_TERMS: Accounting;Advisory Committees;Colorado;Communication;data sharing;Development;Doctor of Philosophy;Epithelium;Etiology;Event;federal policy;Fibroblasts;follower of religion Jewish;Fostering;Goals;Health;Injury;Institution;Institutional Policy;Interdisciplinary Study;Leadership;Lung;lung injury;meetings;MUC5B gene;National Heart, Lung, and Blood Institute;North Carolina;operation;organizational structure;Pathogenicity;Play;prevent;Procedures;Productivity;programs;Pulmonary Fibrosis;Research;Research Personnel;Resource Allocation;Resources;Role;scientific organization;Scientist;Universities;Visit

PROJECT_TITLE: Administrative Core

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


NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research;Lung;Pulmonary Fibrosis

PI_NAMEs: YANG, IVANA V (contact)

PROJECT_TERMS: airway epithelium;Aliquot;alveolar epithelium;Area;Biological;Biopsy;Bronchiectasis;Cell Culture Techniques;Cell Separation;cell type;Cells;Classification;Clinical;clinical phenotype;cohort;Cryopreservation;Cryopreserved Cell;Data;Dissection;Distal;Drug or chemical Tissue Distribution;Epithelial Cells;Epithelium;experimental study;Fibroblasts;Fibrosis;Genotype;Goals;Histopathology;human tissue;Image;Injury;Investigation;Location;Lung;lung injury;MUC5B gene;Participant;Pathologic;Pathologist;Phenotype;phenotypic data;Process;programs;Pulmonary Fibrosis;Quality Control;Radiology Specialty;recruit;Research;Resolution;Resources;risk variant;Role;Sample Size;Scanning;Specimen;Tissue Banks;Tissues;Traction;X-Ray Computed Tomography

PROJECT_TITLE: Human Tissue and Cell Core


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Digestive Diseases;Liver Cancer;Liver Disease;Nanotechnology;Orphan Drug;Radiation Oncology;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: Project Narrative Ultrasound-triggered destruction of intravenous microbubbles has shown promise for sensitizing hepatocellular carcinoma in both preclinical models and in recent therapeutic clinical trials. However, microbubbles are constricted to the tumor blood supply and generate less than ideal shear stresses during cavitation, which may limit the total degree of tumor radiosensitization. This application will investigate the use of two acoustically- sensitive phase change nanodroplet formulations to improve radiosensitization of hepatocellular carcinoma and compare their performance to both micro- and nanobubbles.

PI_NAMEs: EISENBREY, JOHN  (contact)

PROGRAM_OFFICER_NAME: BUCHSBAUM, JEFFREY

PROJECT_TERMS: 3D ultrasound;90Y;Acoustics;Animal Model;Apoptosis;Biological Assay;Blood Vessels;Cancer Etiology;Cell Survival;Ceramides;chemotherapy;clinical translation;constriction;contrast enhanced;Contrast Media;Custom;Data Set;Diameter;Disease;Dose;Early treatment;Eligibility Determination;Encapsulated;Endothelial Cells;Equipment;Evaluation;Excision;experimental study;External Beam Radiation Therapy;Extravasation;fabrication;Fetal Proteins;Fluorocarbons;Formulation;Gases;Glass;hepatocellular carcinoma cell line;Hepatocyte;Human;human model;Image;immune cell infiltrate;Immune response;Immunohistochemistry;Immunotherapy;improved;In Vitro;in vivo;Intravenous;Liquid substance;Liver;liver cancer model;Liver Function Tests;liver transplantation;Magnetic Resonance Imaging;Malignant Neoplasms;Metastatic Neoplasm to the Liver;meter;Microbubbles;Modeling;Modification;mortality;nanobubble;nanoDroplet;Output;Pathology;Patients;Penetration;Performance;phase change;Phospholipids;Physical condensation;Physiologic pulse;Play;Pre-Clinical Model;Primary carcinoma of the liver cells;Production;Progression-Free Survivals;Property;Protocols documentation;Radiation;radiation response;Radiation therapy;Radiation Tolerance;Radiation-Sensitizing Agents;Radioembolization;Radioisotopes;Radiosensitization;randomized, clinical trials;response;Role;Safety;Series;shear stress;subcutaneous;Systemic Therapy;Techniques;Testing;Therapeutic;Therapeutic Clinical Trial;Tissues;treatment response;tumor;tumor growth;Tumor Tissue;tumor vascular supply;Tumor Volume;Tumor-infiltrating immune cells;Ultrasonography;ultrasound;Umbilical vein;United States;vaporization;Vascular Endothelial Cell;Visualization;Work;x-ray irradiation

PROJECT_TITLE: Acoustic Droplet Initiated Radiosensitivity of Hepatocellular Carcinoma


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Clinical Research;Disability Research;Mental Health;Neurosciences;Pain Research;Pediatric

ORG_CITY: STANFORD

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE The purpose of this proposed Midcareer Investigator Award is to mentor the next generation of patient-oriented pediatric pain scientists focused on improving the lives of youth with chronic pain and their parents. The overall objective of this K24 is to expand my current patient-oriented research and mentoring to integrate patient engagement from research to dissemination of care to improve the biobehavioral care of youth with chronic MSK pain. The proposed studies provide the ideal context for enhancing mentorship opportunities via hands- on training and scientific development in the biobehavioral aspects of pediatric chronic pain applying patient- centered methods.

PI_NAMEs: SIMONS, LAURA E (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Adolescent;Affective;Award;biobehavior;biopsychosocial;career;career development;Caring;Characteristics;Child;Childhood;chronic musculoskeletal pain;chronic pain;Clinical;clinical care;Clinical Trials;Cognitive;cohort;Collaborations;Communication;Coupled;Data;Data Analyses;Dedications;Development;digital health;Disabled Children;Ensure;Ethical Issues;Evaluation;evidence base;expectation;Family;Focus Groups;Funding;Future;Health;Health Services Accessibility;Healthcare;human subject;improved;improved outcome;innovation;Intervention;Interview;Leadership;Legal;Lived experience;Mentors;Mentorship;Methods;Mid-Career Clinical Scientist Award (K24);multidisciplinary;multimodality;Musculoskeletal Pain;neglect;neuroimaging;Neurosciences;next generation;opioid epidemic;Outcome;Pain;Pain management;Parents;Participant;patient engagement;patient oriented;patient oriented research;Patients;Pediatric Research;Personal Satisfaction;Persons;Physical therapy;Physicians;Process;Provider;Psychology;Recovery;recruit;Refractory;Research;Research Methodology;Research Personnel;Resources;response;Scientist;Sentinel;Site;skills;success;Teenagers;theories;Time;Training;Translating;United States National Institutes of Health;virtual;Work;years lived with disability;Youth

PROJECT_TITLE: Mentoring and Research in Biobehavioral Aspects of Pediatric Pain

STUDY_SECTION: AMS

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Special Grants Study Section[AMS]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Schizophrenia;Serious Mental Illness;Social Determinants of Health

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The proposed research will test the hypothesis that objective social isolation and loneliness are linked to neurobehavioral mechanisms involved in social perception and motivation in individuals with and without serious mental illness. Moreover, it will investigate the specific dynamic interactions among these experiences in daily life and how they, and their neurobehavioral predictors, are linked to cardiometabolic health. The findings of this project could provide novel targets for therapeutics aimed at improving health and overall quality of life in individuals with serious mental illnesses, as well as quantitative phenotypes for use in early detection efforts.

PI_NAMEs: FULFORD, DANIEL C;HOLT, DAPHNE J (contact)

PROGRAM_OFFICER_NAME: LEITMAN, DAVID ISAAC

PROJECT_TERMS: Address;Adult;Affect;Amygdaloid structure;Area;Basal Ganglia;Behavior;behavior prediction;Behavioral;Behavioral Mechanisms;Blood Pressure;Body mass index;Brain;cardiometabolism;Cellular Phone;Chronic;Data;design;Diagnosis;digital assessment;Disease;Early Diagnosis;Ecological momentary assessment;experience;Face;follow-up;Functional Magnetic Resonance Imaging;General Population;Health;Heart Rate;high body mass index;Hippocampus;Human;Impairment;improved;in vivo;indexing;Individual;Individual Differences;inflammatory marker;interest;Intervention;intimate behavior;Life;life span;Link;Loneliness;longitudinal design;Measures;medial temporal lobe;Medical;Metabolic Marker;mobile computing;Modeling;Morbidity - disease rate;mortality;Motivation;neural;neural correlate;neurobehavioral;neurobiological mechanism;neuroimaging;Neurophysiology - biologic function;new therapeutic target;novel;novel strategies;Outcome;Participant;personalized intervention;Persons;Phenotype;poor health outcome;preference;prevent;Process;psychologic;Psychotic Disorders;Publishing;Quality of life;Recording of previous events;Reporting;Research;response;Rewards;Schizophrenia;severe mental illness;smartphone based assessment;social;Social Behavior;social contact;social determinants;Social Interaction;Social isolation;Social Network;Social Perception;social space;Stimulus;Testing;Thalamic structure;Time;trait;Variant;Withdrawal;Work

PROJECT_TITLE: Stable and dynamic neurobehavioral phenotypes of social isolation and loneliness in serious mental illness


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Recently, SPI1 gene (encoding PU.1 protein) was reported as a genetic risk factor of Alzheimer’s disease in large-scale genome-wide association studies. PU.1 is a transcription factor that is mainly expressed by myeloid lineage cells, such as microglia, monocytes, and macrophages. The overarching goal of this application is to understand the role of PU.1 in microglia and the mechanisms by which PU.1 contributes to the pathogenesis of Alzheimer’s disease using systems biology approaches.

PI_NAMEs: KIM, JUNGSU  (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Address;Affect;Age;Alzheimer like pathology;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Amyloid;Amyloid beta-Protein;Amyloid deposition;amyloid pathology;Amyloidosis;Animal Model;astrogliosis;Brain;Candidate Disease Gene;Cell Line;Cell Lineage;Cells;chemokine;Collaborations;Communities;conditional knockout;Core Facility;cytokine;Data;data resource;Data Set;Disease;disease phenotype;Disease Progression;Down-Regulation;Electrophysiology (science);epigenomics;experience;experimental study;Frontal gyrus;Genes;genetic analysis;genetic risk factor;Genetic study;Genetic Transcription;genome wide association study;genome-wide;Gliosis;Goals;Human Genetics;human induced pluripotent stem cells;immune function;Immune response;Immune system;In Vitro;in vitro activity;in vivo;Inflammatory;innovative technologies;insight;knock-down;Knock-in Mouse;Knockout Mice;Knowledge;laboratory facility;lipid metabolism;Macrophage;Magnetic Resonance Imaging;Mediating;Metabolism;Methods;Microglia;Molecular;Molecular Genetics;monocyte;mouse model;multi-electrode arrays;multiple omics;Myelogenous;Neurons;Neurosciences Research;new therapeutic target;Pathogenesis;Pathology;Pathway interactions;Peptides;Phagocytes;Phagocytosis;Phenotype;Play;Positron-Emission Tomography;protein aggregation;Proteins;Proteomics;Reporting;response;risk variant;Role;selective expression;Senile Plaques;single-cell RNA sequencing;SPI1 gene;superresolution microscopy;Systems Biology;Testing;therapy development;transcription factor;transcriptomics;uptake

PROJECT_TITLE: Molecular genetic analyses of transcriptional dysregulation in Alzheimers disease

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: Clinical Research;Genetics;Human Genome;Lung;Pulmonary Fibrosis

PI_NAMEs: DOBRINSKIKH, EVGENIA  (contact)

PROJECT_TERMS: Address;Apoptosis;Autophagocytosis;Biological Assay;Cell Aging;Collaborations;Collagen;Complement;Data;Data Analyses;data management;design;digital;Doctor of Philosophy;endoplasmic reticulum stress;Fibrillar Collagen;Fibrosis;Fluorescence;Gene Expression Profile;Goals;Human;Image;Image Analysis;Immunofluorescence Immunologic;Immunohistochemistry;improved;In Situ Hybridization;Individual;Investigation;Label;Lung;lung injury;Messenger RNA;microscopic imaging;Mus;nano-string;Pattern;Phenotype;programs;Proteins;Pulmonary Fibrosis;Research;Resources;Sampling;second harmonic generation imaging;Services;single-cell RNA sequencing;Specimen;Stains;Structure of parenchyma of lung;transcriptome;transcriptome sequencing;whole slide imaging

PROJECT_TITLE: Imaging and Image Analysis Core


NIH_SPENDING_CATS: Clinical Research;Drug Abuse (NIDA only);HIV/AIDS;Infectious Diseases;Substance Misuse

PHR: Project Narrative It is well known that a small pool of persistently HIV-infected cells is the major obstacle to curing HIV infection. This study will examine the changes in the size of the HIV reservoir in samples collected from participants of the MERLIN acute HIV infection study (Lima, Peru) over approximately 7 years of treatment with anti-retroviral drugs. The goal is to identify features of infected cells and of HIV itself that affect the body’s ability to reduce and possibly eliminate the HIV reservoir.

PI_NAMEs: CHOMONT, NICOLAS ;DUERR, ANN C (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, DIANE M

PROJECT_TERMS: Acceleration;Acute;Affect;Anti-Retroviral Agents;Antibodies;Antigen Presentation;Antigens;Autologous;BCL2 gene;BCL2L1 gene;Biological Assay;CD4 Positive T Lymphocytes;Cells;Characteristics;Chromatin;Clonal Expansion;Clonality;cohort;Coupled;Couples;Cryopreservation;Data;decay acceleration;Early Diagnosis;Ensure;experimental study;fitness;FOXO3A gene;Future;Genetic Transcription;Genome;genome sequencing;Goals;Half-Life;HIV;HIV envelope protein;HIV Genome;HIV Infections;immune checkpoint;immune clearance;Immunologics;Individual;Infection;integration site;Leukapheresis;Ligands;Longterm Follow-up;Maintenance;Measures;Mediating;Memory;Molecular;Nature;NCOA6 gene;novel strategies;Participant;Persons;Pharmaceutical Preparations;Phenotype;Predisposition;Process;Production;Proliferating;Proteome;Proviruses;Randomized;Reporting;Resistance;response;Sampling;Serpins;Source;Testing;Time;tool;Transforming Growth Factor beta;Viral;Viral Genome;Virus;whole genome

PROJECT_TITLE: Identifying vulnerabilities in the long-lived HIV reservoir to accelerate its decay


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_CITY: Chicago

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Pregnant and postpartum women, particularly low-income women of color, are at increased risk for developing mood and anxiety disorders. This study investigates the association of specific hormonal factors with mood and anxiety symptoms in low-income pregnant women of color. Findings can help to identify biological factors contributing to perinatal mood and anxiety disorders in at-risk populations.

PI_NAMEs: EISENLOHR-MOUL, TORY ANNE;MAKI, PAULINE M (contact);PINNA, GRAZIANO

PROGRAM_OFFICER_NAME: LAWHORN, COLLENE

PROJECT_TERMS: Acute;Adverse effects;Affect;Affective Symptoms;Allopregnanolone;antenatal;Anxiety;Anxiety Disorders;anxiety symptoms;Behavior;Biological Factors;Blood;cohort;Color;comorbidity;Data;depressive symptoms;Detection;Diagnosis;early pregnancy;emotional symptom;Estradiol;ethnic minority;Etiology;experimental study;Failure;FDA approved;Female;First Pregnancy Trimester;GABA Receptor;Hormonal;Hormones;Human;Impairment;improved;Individual;Infant;Infant Health;intravenous injection;Isomerism;Latina;Link;Longitudinal Studies;Low Birth Weight Infant;Low income;Low Income Population;Maternal Health;Measures;Mental Depression;Mental Health;Methods;Mood Disorders;mood symptom;Moods;Mothers;neural circuit;neurosteroids;Participant;Pathogenesis;Patients;Pattern;people of color;Perinatal;perinatal period;peripartum depression;Peripheral Blood Mononuclear Cell;personalized medicine;Play;Population;Populations at Risk;positive allosteric modulator;Postpartum Depression;Postpartum Period;Postpartum Women;pre-clinical;Pre-Clinical Model;Predisposition;Pregnancy;Pregnanolone;pregnant;Pregnant Women;Premature Birth;prevent;Progesterone;Publishing;racial minority;receptor;recruit;Regulation;Risk;Rodent Model;Role;Sample Size;Second Pregnancy Trimester;Steroid Receptors;Stress;Symptoms;Testing;Third Pregnancy Trimester;Time;Translating;Trauma;Visit;Withdrawal;Withdrawal Symptom;women of color;Work

PROJECT_TITLE: Perinatal Affective Symptoms, Neuroactive Steroids, and GABA Receptor Plasticity in Women of Color

STUDY_SECTION: APDA

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


NIH_SPENDING_CATS: Clinical Research;Genetics;Human Genome;Lung;Networking and Information Technology R&D (NITRD);Pulmonary Fibrosis

PI_NAMEs: PELJTO, ANNA  (contact)

PROJECT_TERMS: Bioinformatics;Biometry;Cell Culture Techniques;Cells;Collaborations;Communication;Complex;Consultations;cost;Cost Savings;Data;Data Analyses;data cleaning;data exchange;data format;data integration;data integrity;data management;Data Management Resources;data repository;Data Set;data sharing;data sharing networks;Data Storage and Retrieval;Database Management Systems;Databases;design;Development;Development Plans;digital imaging;Documentation;Ensure;Etiology;experience;experimental study;Genomics;Goals;Group Meetings;Human;Individual;Interdisciplinary Study;Knowledge;Lead;lung injury;meetings;member;Methods;Mus;organizational structure;Positioning Attribute;Process;Productivity;programs;Protocols documentation;Pulmonary Fibrosis;Quality Control;Recording of previous events;Reporting;repository;Research;Research Design;Research Personnel;Resource Sharing;Resources;Secure;single-cell RNA sequencing;skills;Statistical Data Interpretation;Testing;transcriptome sequencing;transcriptomics;Work

PROJECT_TITLE: Data Management and Analysis Core


NIH_SPENDING_CATS: Clinical Research;Genetics;Human Genome;Lung;Pulmonary Fibrosis;Rare Diseases

PI_NAMEs: GERBER, ANTHONY N (contact)

PROJECT_TERMS: activating transcription factor;Address;Aging;airway epithelium;Area;ATAC-seq;Binding;biological adaptation to stress;Bronchioles;Cell Culture Techniques;Cell Differentiation process;Cells;ChIP-seq;Chromatin;chromatin remodeling;Collaborations;Cues;Data;Death Rate;Disease;Distal;DNA;endoplasmic reticulum stress;Enhancers;Epigenetic Process;epigenetic regulation;Epithelial Cells;Epithelium;Etiology;European;Event;Family;Fibroblasts;Gene Expression Regulation;Genetic Transcription;genome-wide;Genomics;Genotype;Human;human model;human tissue;idiopathic pulmonary fibrosis;Injury;Investigation;knock-down;lung injury;Malignant Neoplasms;Methods;Modeling;Molecular;mouse model;MUC5B gene;Mus;new therapeutic target;Odds Ratio;overexpression;Particulate;Pathogenesis;Phenotype;Population;Process;programs;Pulmonary Fibrosis;recruit;Regulation;response;Response Elements;response to injury;Risk;Risk Factors;RNA;Role;Sampling;Site;Smoking;Terminal Bronchiole;Testing;Tissue Sample;Transcript;transcription factor;Transcriptional Regulation;Work;XBP1 gene

PROJECT_TITLE: Maladaptive epigenetic control of MUC5B transcription in pulmonary fibrosis


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: CHICAGO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Project Narrative Older adults are prone to cognitive impairment due to neurodegenerative diseases and other medical conditions with increasing age. Early identification of cognitive impairment may be identified by decision- making capacity in a variety of domains, from finance, functional outcomes, medical decision-making, and more. Based on a national consortium of interdisciplinary experts, ARMCADA will develop and validate a set of decision-making measures across the full spectrum of cognitive and decision-making competencies and incorporate nationwide dissemination into existing studies. We will also facilitate the nationwide public dissemination of these measures to target the early identification of older adults with cognitive impairment and evaluate the efficacy of potential interventions aimed to mitigate cognitive decline.

PI_NAMEs: GERSHON, RICHARD  (contact);WEINTRAUB, SANDRA

PROGRAM_OFFICER_NAME: TREVINO, MELISSA

PROJECT_TERMS: Age;Age-associated memory impairment;Aging;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Area;Behavioral;Caregivers;Cellular Phone;Cognitive;cognitive ability;Cognitive aging;Competence;Consent;Contracts;Decision Making;decision-making capacity;design;Detection;Development;Dimensions;Early identification;early screening;Education;efficacy evaluation;Elder Abuse;electronic health record system;experience;Family;financial decision making;functional outcomes;Funding;Goals;health disparity;healthy aging;Impaired cognition;Impairment;Independent Living;Infrastructure;Institution;Intervention;Legal;Measurement;Measures;Medical;Minority;Modeling;Neurobehavioral Manifestations;Neurodegenerative Disorders;Neurologic;Neurosciences;normal aging;older adult;Outcome Measure;Participant;pathological aging;Patients;Performance;Pilot Projects;Procedures;psychosocial;Public Domains;Quality of life;Reporting;Research;Research Personnel;Review Literature;Sampling;Science;screening;Series;skills;Standardization;Surveys;Systems Development;Taxonomy;theories;Time;United States National Institutes of Health;United States Preventative Services Task Force;Universities;Validation

PROJECT_TITLE: ARMCADA - Advancing Reliable Measurement in Cognitive Aging and Decision-making Ability


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: DENVER

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF DENVER (COLORADO SEMINARY)

PHR: Project Narrative Multicellular life is three-dimensional in nature, but is often reduced to a 2D planar data set to simplify analysis. Here, we will develop the methods to determine the true 3D behaviors that direct cellular motility in epithelial sheets. This is critical as epithelial tissues must be able to dynamically remodel their dimensions to generate adult tissue morphologies during development, as well as permit new cells to replace aging cells during homeostasis.

PI_NAMEs: BLANKENSHIP, JAMES TODD (contact);LOERKE, DINAH

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: 3-Dimensional;Actins;Actomyosin;Address;Adhesives;Adopted;Adult;Affect;Apical;Architecture;Area;Automobile Driving;Behavior;Biological Models;Cell Aging;cell behavior;cell cortex;cell dimension;cell motility;Cell Shape;Cell surface;Cell Volumes;Cells;Cellular biology;cellular imaging;Columnar Epithelium;Computer Analysis;computerized tools;Coupled;Cytoplasm;Data;Data Set;Development;Dimensions;Disease;Drosophila genus;Elasticity;Embryo;embryo cell;Environment;Epithelial Cells;Epithelium;Event;F-Actin;fly;Gastrula;gastrulation;Generations;Goals;Growth;Homeostasis;Image;imaging capabilities;in vivo;Individual;Intercalated Cell;intercalation;Knowledge;Lateral;Life;Light;Location;Maps;Measurement;Measures;Mechanics;Methods;Microscopy;Molecular;Molecular Conformation;Morphogenesis;Morphology;Movement;Myosin ATPase;Myosin Type II;Nature;novel;Population;Population Distributions;Positioning Attribute;Process;Proteins;Resolution;Shapes;spatiotemporal;Speed;Stratum Basale;Surface;Surveys;System;Testing;Three-dimensional analysis;Time;Tissues;tool;Viscosity

PROJECT_TITLE: Volumetric analysis of epithelial morphogenesis with high spatiotemporal resolution

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Brain Disorders;Emerging Infectious Diseases;Genetics;Human Genome;Infectious Diseases;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases;Transmissible Spongiform Encephalopathy (TSE)

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: PROJECT NARRATIVE Prion disease is a rapidly fatal neurodegenerative disease that arises from a single protein, the native prion protein (PrP), which post-translationally converts into a misfolded, pathogenic prion; lowering PrP in the brain is robustly protective against prion disease, but difficult to achieve at the needed whole-brain scale with large gene, biologic or even oligonucleotide therapeutics. Having recently identified two small molecules that potently lower PrP with good proteomic selectivity through unknown mechanisms, we will combine targeted genetic perturbations and molecular biology follow-up with proteome-, transcriptome- and genome-wide methods in order to illuminate these novel mechanisms governing PrP expression, while also probing their in vivo relevance. Together, this work will uncover one or more new pathways networked to prion biology and provide much-needed new directions for translational efforts against this deadly disease, potentially offering clues to aid development of the first PrP-lowering small molecule drug.

PI_NAMEs: VALLABH, SONIA MINIKEL (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: analog;Antibodies;Antisense Oligonucleotides;Biological;Biological Assay;Biological Availability;Biology;Brain;Cell Separation;Cell surface;Cells;Collaborations;Complement;conformer;CRISPR screen;Development;Diabetes Mellitus;Disease;Distal;Dose;Drug Kinetics;drug testing;Ectopic Expression;Enzyme-Linked Immunosorbent Assay;Epitopes;Exposure to;follow-up;Genes;Genetic;genome-wide;Genomics;Goals;Guide RNA;Immunofluorescence Immunologic;in vivo;Infection;Interphase Cell;knock-down;Knock-out;Lead;Libraries;Lysosomes;Malignant Neoplasms;Mediating;Methods;Molecular Biology;mouse genome;multicatalytic endopeptidase complex;Mus;Neurodegenerative Disorders;non-prion;novel;oligonucleotide therapeutics;Organ;overexpression;Pathogenicity;Pathway interactions;Penetration;Peripheral;Pharmaceutical Preparations;pharmacologic;Phenotype;Population;preclinical development;Prion Diseases;Prions;Process;Property;Protein Biosynthesis;protein expression;Proteins;Proteolytic Processing;Proteome;proteomic signature;Proteomics;PrP;Regulation;Resistance;response;Series;small molecule;Specificity;System;Testing;Therapeutic;Time;Tissues;tool;transcriptome;transcriptome sequencing;transcriptomics;Transfection;uptake;Western Blotting;Work

PROJECT_TITLE: Mechanism of Action of Prion Protein-Lowering Small Molecules

STUDY_SECTION: DDNS

STUDY_SECTION_NAME: Drug Discovery for the Nervous System Study Section[DDNS]


PROJECT_TERMS: Affect;Aging;airway epithelium;alveolar epithelium;Apoptosis;arm;Autophagocytosis;biological adaptation to stress;biophysical properties;Biopsy;Bleomycin;Bronchioles;Caliber;Cell Aging;cell injury;Cell Mobility;Cell Proliferation;Cells;Development;Differentiation Antigens;Distal;endoplasmic reticulum stress;Epithelial Cells;epithelial injury;Epithelium;Etiology;Event;Experimental Models;Exposure to;Fibroblasts;Fibrosis;Functional disorder;gain of function;Genetic;Genetic Transcription;Goals;Heterogeneity;Immunofluorescence Immunologic;In Situ Hybridization;In Vitro;in vivo;Individual;Inflammation;Injury;injury and repair;innovation;Link;Lung;lung development;Lung Diseases;lung injury;Maps;Modeling;MUC5B gene;Mucins;Mus;novel strategies;Operative Surgical Procedures;overexpression;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Patients;Pattern;pharmacologic;Phenotype;Polymers;Population;Predisposition;prevent;Production;promoter;Proteins;proteostasis;Pulmonary Fibrosis;recruit;Research;Research Personnel;response;response to injury;Risk;Risk Factors;Role;Structure of parenchyma of lung;Testing;tissue repair;Tobacco smoke;transcriptome sequencing;transcriptomics;Transgenic Mice;Variant;wound healing;XBP1 gene

PROJECT_TITLE: Endoplasmic reticulum stress in MUC5B-driven lung fibrosis


ORG_CITY: BIRMINGHAM

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Narrative Metabolic reprogramming by oncogenes and tumor suppressors has a central role in the initiation and progression of cancers, including high-risk neuroblastoma. In this application, we will investigate a new mechanism by which the oncogene MYCN integrates cholesterol synthesis with nucleotide and amino acid metabolism, which may suggest new therapeutic strategies against this deadly pediatric cancer.

PI_NAMEs: DING, HAN-FEI  (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Acetyl Coenzyme A;alpha ketoglutarate;amino acid metabolism;Amino Acids;Animal Model;anti-cancer research;Automobile Driving;Biochemical;biomarker identification;cancer cell;Cancer Cell Growth;Carbon;carboxylation;Cell Line;Cell Proliferation;Cells;Child;Cholesterol;Cholesterol Homeostasis;Clinical;Code;Combined Modality Therapy;Data;Development;Down-Regulation;Enzyme Inhibitor Drugs;enzyme pathway;Enzymes;Feedback;Gene Expression Profiling;Genes;Genetic Transcription;Genomics;Glutamine;Glycine;Goals;Growth;high risk;Human;in vivo;Knowledge;Link;Malignant Childhood Neoplasm;Metabolic;Metabolic Pathway;Metabolism;mevalonate;Modeling;Molecular;mouse model;Mus;MYCN gene;neoplastic cell;Neuroblastoma;neuroblastoma cell;novel strategies;novel therapeutic intervention;nucleotide metabolism;Nucleotides;Oncogenes;Oncogenic;Output;Pathway interactions;patient derived xenograft model;Population;Prediction of Response to Therapy;Primary Neoplasm;Process;Production;programs;Proliferating;Publishing;Repression;Research;Role;self-renewal;Serine;small hairpin RNA;Source;stable isotope;Survival Rate;Testing;Therapeutic;Therapeutic Intervention;Tracer;transcription factor;Transcriptional Activation;tumor;tumor progression;Tumor Suppressor Proteins;Tumorigenicity;Up-Regulation;Xenograft procedure

PROJECT_TITLE: Linking nucleotide and amino acid metabolism to cholesterol synthesis by MYCN


NIH_SPENDING_CATS: Biotechnology;Cancer

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative The goal of this proposal is the development of fundamentally new and more effective approaches to cancer therapy and disease pharmacology in general that will complement and enhance existing therapies. This project will develop new pharmacophores with the capacity to target the interactions between proteins and membranes directly, explore the modulation of binding properties at the protein-membrane interface, and screen for new principles governing cell permeability of small molecules which is a fundamental requirement for the bioactivity of most drugs. Combined, these approaches will create new classes of pharmacophores and methods to address cancer signaling (e.g. KRAS, PI3K, PCK etc), membrane-integrated targets (GPCRs, ion channels, enzyme- linked receptors, transporters etc.), and soluble intracellular targets at large.

PI_NAMEs: MORSTEIN, JOHANNES  (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Address;anti-cancer research;Area;Binding;Biological;Biological Products;biophysical properties;Cancer Biology;cancer immunotherapy;cancer pharmacology;cancer therapy;career;Cell membrane;Cell Membrane Permeability;Cells;Chemical Structure;Chemistry;combinatorial;combinatorial chemistry;Complement;Conceptions;convict;Data;design;Development;Diffusion;Disease;Drug Design;drug discovery;Drug Targeting;Electrostatics;Endocytosis;Enzymes;Event;experience;FRAP1 gene;G-Protein-Coupled Receptors;Goals;Growth;Guanosine Triphosphate Phosphohydrolases;high throughput screening;holistic approach;Human;inhibitor;innovation;insight;Interdisciplinary Study;Ion Channel;KRAS2 gene;Lateral;Libraries;Link;Lipids;lipophilicity;Liposomal Doxorubicin;Malignant Neoplasms;MAP Kinase Gene;Membrane;Membrane Proteins;Mentors;Mentorship;Methods;nanotherapy;Natural Products;Nature;new therapeutic target;novel;novel strategies;Pathway interactions;Permeability;Pharmaceutical Preparations;pharmacologic;Pharmacology;pharmacophore;Phosphotransferases;PIK3CG gene;Process;Property;Proteins;receptor;recruit;Research;RNA vaccine;Role;screening;Signal Pathway;Signal Transduction;Site;skills;small molecule;Structure-Activity Relationship;Testing;Training;uptake;WNT Signaling Pathway

PROJECT_TITLE: Targeting Cancer at the Protein-Membrane Interface


NIH_SPENDING_CATS: Clinical Research;Lung;Prevention;Pulmonary Fibrosis;Rare Diseases

PI_NAMEs: RICHES, DAVID W. (contact)

PROJECT_TERMS: Ablation;Address;airway epithelium;Alleles;Alveolar;alveolar epithelium;Apoptosis;Apoptotic;Cells;Chronic;Cyst;Development;Distal;endoplasmic reticulum stress;Epithelial Cells;epithelial injury;Epithelium;Event;Extrinsic allergic alveolitis;Fibroblasts;Fibrosis;gain of function;genetic variant;Goals;Human;idiopathic pulmonary fibrosis;In Vitro;in vivo;Individual;Induction of Apoptosis;Injury;innovation;insight;interstitial;Interstitial Lung Diseases;Knowledge;Learning;Lung;lung injury;Maps;Medial;Methods;Minor;Modeling;mouse model;MUC5B gene;Mus;novel;Pathogenesis;Pathologic;Patients;Predisposition;prevent;Prevention;profibrotic fibroblast;promoter;Proteins;Pulmonary Fibrosis;Repression;Resources;response;Rheumatoid Arthritis;Risk Factors;Role;System;Testing;Tissues;Variant

PROJECT_TITLE: Targeting early events in MUC5B-driven lung injury and fibrosis


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health

ORG_CITY: AMHERST

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: PROJECT NARRATIVE The NIMH Research Domain Criteria (RDoC) represents a breakthrough framework for understanding the etiology of mental disorders, but it has no clinical traction at present. Of the RDoC units of analysis, self-report measures can be most feasibly implemented in a clinic, but many self-reports for RDoC’s Negative Valence Systems (NVS) constructs have psychometric shortcomings and lack normative data. We seek to develop psychometrically sound, brief, and validated self-report measures (questionnaires and interviews) of each NVS construct with strong normative data, contributing to advancements in psychiatric research, diagnosis, and intervention.

PI_NAMEs: KOTOV, ROMAN I;SIMMS, LEONARD JAY (contact)

PROJECT_TERMS: Acute;Address;Adult;Age;Anxiety;appetite loss;Behavior;Catalogs;Characteristics;Clinic;Clinical;clinical application;clinical care;Clinical Research;clinical translation;Common Data Element;Communities;Data;Data Collection;design;Development;Diagnosis;Dimensions;disease classification;Equation;ethnic diversity;Ethnic Origin;Etiology;evidence base;flexibility;Goals;handheld mobile device;Health Insurance Portability and Accountability Act;instrument;Internet;Intervention;Interview;Judgment;Link;Longitudinal Studies;Maps;Measures;Mental disorders;Methods;Modeling;Monitor;National Institute of Mental Health;Negative Valence;Outcome;Outpatients;Participant;Patient Self-Report;Patients;Phase;Physiological;Physiology;Population;Process;Psychometrics;Psychopathology;Psychophysiology;Questionnaires;recruit;Research;Research Domain Criteria;Research Personnel;Resolution;response;Sampling;Science;screening;Self Administration;sex;Site;sound;Source;Specific qualifier value;Symptoms;System;Task Performances;Taxonomy;Testing;theories;tool;Traction;trait;Walking

PROJECT_TITLE: Development of Negative Valence Measures


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Clinical Research;Endocrine Disruptors;Genetics;Human Genome;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative It is increasingly recognized that exposures to toxicants affect health and disease by not only mutating genes, but also by modifying the epigenome, alterations to DNA that are heritable and lead to disease when deregulated. Our research will advance the understanding of the effects of perinatal exposures (e.g. metals such as lead and endocrine disrupting chemicals such as phthalates) on the epigenome and health risks as well as develop new tools, based on the PIWI-interacting RNA (piRNA) system to transform precision environmental health.

PI_NAMEs: DOLINOY, DANA  (contact)

PROGRAM_OFFICER_NAME: TYSON, FREDERICK L

PROJECT_TERMS: Advanced Development;Affect;Animal Model;Animals;Azacitidine;Belief;Biological Availability;Birth;Blood;Brain;cell type;Cells;Chromatin Structure;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Disease;Disease susceptibility;disorder risk;DNA;DNA Methylation;Endocrine;Endocrine Disruptors;Environment;Environmental Health;Epidemiology;Epigenetic Process;epigenome;epigenome editing;epigenomics;experimental study;Exposure to;flexibility;Gene Expression;Genes;Germ Lines;Goals;Health;Heritability;Human;Human Cell Line;human tissue;imprint;In Vitro;in vivo;innovation;Lead;Life;Malignant Neoplasms;Metals;Mitotic;Modification;mouse model;Mus;Mutate;Outcome;Perinatal Exposure;phthalates;Physiological;piRNA;Research;Research Support;Resources;Risk;RNA;Rodent;Sampling;sex;Somatic Cell;System;Technology;Therapeutic;Tissues;tool;toxicant;Toxicant exposure;Toxicology;Training;transcription activator-like effector nucleases;Untranslated RNA;Vision

PROJECT_TITLE: Environmental Epigenomics and Precision Environmental Health


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease

ORG_CITY: CHARLESTON

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: Liver damage leads to scaring of the liver in a pathologic process known as cirrhosis. This leads to many different complications resulting from high pressure in the major vein feeding the liver; this leads to severe intestinal bleeding, fluid build-up in the abdomen, and others – and to a poor quality of life. This proposal seeks to understand the cause of the high-pressure liver complications and ultimately to provide insights that will lead to new therapies to treat this problem.

PI_NAMEs: ROCKEY, DON C. (contact)

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: Abdomen;Area;Arrestins;beta-arrestin;Binding;Blood flow;Cellular biology;Cicatrix;Cirrhosis;Coin;Complex;constriction;Data;Defect;Discontinuous Capillary;Disease;Endothelial Cells;endothelial dysfunction;Etiology;experimental study;Extrahepatic;feeding;Focal Adhesions;Funding;Future;G-Protein-Coupled Receptors;genetic regulatory protein;GIT1 gene;Goals;Hemorrhage;Hepatic Stellate Cell;Human;in vivo;injured;innovation;insight;Intestines;intrahepatic;Laboratories;Liquid substance;Liver;Liver diseases;Liver Fibrosis;liver injury;Mediating;Medical;Molecular;Morbidity - disease rate;mortality;new therapeutic target;Nitric Oxide;NOS3 gene;novel;novel therapeutics;Pathogenesis;Pathologic Processes;Pathway interactions;Patients;paxillin;Phenotype;Phosphorylation;Play;Portal Hypertension;Post-Translational Protein Processing;Post-Translational Regulation;pressure;Process;Production;Proteins;Quality of life;Regulation;Resistance;Role;Seminal;Series;SH3 Domains;Signal Pathway;Signal Transduction;Signaling Molecule;System;Testing;Therapeutic;Translating;Translational Regulation;translational therapeutics;Vascular Diseases;vasoconstriction;Vasoconstrictor Agents;Vasodilation;Vasodilator Agents;Veins;Work

PROJECT_TITLE: A Molecular Approach to the Pathogenesis of Portal Hypertension

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


NIH_SPENDING_CATS: Cancer;Genetics;Skin Cancer

ORG_DEPT: DERMATOLOGY

PHR: Project Narrative / Relevance Drug resistance remains common in advanced basal cell carcinomas (BCC), and while we have shown that the polarity kinase atypical protein kinase C (PRKCi) amplifies Gli activity and confers resistance, the mechanism remains unknown. We have found that isoforms of the Lamina-Associated Polypeptide 2 (LAP2) bind to the Gli and protect it from degradation or nuclear export while PRKCi prevents nucleoplasmic LAP2-HDAC1-GLI degradation and promotes movement from the nuclear envelope to chromatin. Completion of the project will deepen our mechanistic insights into transcription factor trafficking and regulation in the nucleus, help optimize rational BCC therapy, and identify new therapeutic targets.

PI_NAMEs: ORO, ANTHONY E (contact)

PROGRAM_OFFICER_NAME: KOCH, PETER

PROJECT_TERMS: Address;atypical protein kinase C;Basal cell carcinoma;Binding;Biological Assay;Cell Nucleus;Chemoresistance;Chromatin;Complex;Cytoskeleton;Deacetylation;Drug resistance;Effectiveness;efficacy evaluation;Epigenetic Process;Erinaceidae;Exhibits;Genetic Epistasis;Hair follicle structure;HDAC1 gene;Human;inhibitor;insight;Invaded;Lysine;Malignant Neoplasms;member;Movement;Mus;Mutation;Neoplasm Metastasis;new therapeutic target;novel;Nuclear;Nuclear Envelope;Nuclear Export;Nucleoplasm;Operative Surgical Procedures;Pathway interactions;Phosphotransferases;Play;polypeptide;Positioning Attribute;Prevalence;prevent;progenitor;Protein Isoforms;Protein Kinase C;Proteomics;Publishing;Reader;Reagent;Regulation;Resistance;resistance mechanism;response;Role;Signal Pathway;Site;Skin Cancer;Structure;Surface;Testing;trafficking;transcription factor;tumor;Work;Zinc Fingers

PROJECT_TITLE: Regulating Gli Function in Hair Follicle Progenitors

STUDY_SECTION: ACTS

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


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Aging;Genetics;Rare Diseases

ORG_CITY: CLARKSBURG

ORG_NAME: TELOHEALTHDX LLC

ORG_STATE: MD

PHR: Project Narrative  Telomere-associated diseases, including telomere biology disorders (TBDs), are prevalent among the aging population. TBDs have diverse clinical manifestations and are characterized by multisystemic phenotypes that pose a major challenge in diagnosis. The proposed study will develop a low-cost and accurate telomere test to improve the diagnosis and management of telomere-associated diseases.

PI_NAMEs: WANG, YING ;ZHENG, YUN-LING  (contact)

PROGRAM_OFFICER_NAME: TSAP, LEONID V

PROJECT_TERMS: age group;Aging;aging population;aging related disease;Aplastic Anemia;assault;Authorization documentation;Biological Assay;Biology;Blood;Blood specimen;Bone marrow failure;Case/Control Studies;Cell Line;cell type;Cells;Clinical;Clinical Research;Complex;cost;Data Analyses;Defect;design;Diagnosis;Diagnostic;diagnostic accuracy;Diagnostic tests;diagnostic tool;Disease;DNA;Dyskeratosis Congenita;Early Diagnosis;Flow Cytometry;Fluorescent in Situ Hybridization;Foundations;Genetic;genetic testing;Genomic DNA;Goals;Human;human population study;idiopathic pulmonary fibrosis;improved;Incidence;Individual;Insurance;Laboratories;Legal patent;Length;Leukocytes;Liver Cirrhosis;magnetic beads;Malignant Breast Neoplasm;Malignant Neoplasms;Marketing;Measurement;Measures;Membrane;Methods;Molecular;Mononuclear;multiorgan damage;National Institute of Environmental Health Sciences;Nature;next generation;Normal Range;Other Genetics;Pathology;Patients;Phase;phase 1 study;phase 2 study;Phenotype;Population;Premature aging syndrome;Procedures;Protocols documentation;Pulmonary Fibrosis;Research;Research Contracts;Sampling;Science;screening;Screening procedure;Sensitivity and Specificity;Series;service organization;Silicon Dioxide;software development;Standardization;Technology;telomere;Testing;Time;Tissues;United States National Institutes of Health;Whole Blood

PROJECT_TITLE: Single telomere length analysis using DNA array and FISH: a low-cost and accurate test for telomere-associated diseases

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-G (15)]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Orphan Drug;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: GREENVILLE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: EAST CAROLINA UNIVERSITY

PHR: PROJECT NARRATIVE Ectodermal dysplasias linked to mutations in the TP63 gene are characterized by severe skin erosions. The erosions subject patients to life-threatening infections and decrease patients’ quality of life. This proposal aims to uncover the pathological mechanisms causing these devastating skin manifestations, allowing for the identification of novel therapeutic strategies to treat patients.

PI_NAMEs: SALOIS, MADDISON  (contact)

PROGRAM_OFFICER_NAME: VINCENT, ISAAH S

PROJECT_TERMS: 3-Dimensional;Abnormal Keratinocyte;Acceleration;Adhesions;Affect;appendage;Basement membrane;Behavior;Cell Culture Techniques;Cell Line;Cells;cleft lip and palate;Culture Media;Data;Defect;Development;developmental disease;Differentiation Antigens;Disease;Disease Pathway;DNA Binding Domain;Down-Regulation;Ectodermal Dysplasia;Epidermis;experimental study;Exposure to;Extracellular Matrix;Foundations;Gene Expression;Genes;Hemidesmosomes;Human;Image;Impairment;In Vitro;induced pluripotent stem cell;Infection;Integrins;keratinocyte;keratinocyte differentiation;knock-down;Laboratories;Lead;Left;lentivirally transduced;Lentivirus;Life;Ligands;Link;Location;Maintenance;migration;Missense Mutation;Modeling;molecular pathology;Multiprotein Complexes;mutant;Mutation;Mutation Analysis;new therapeutic target;novel;novel therapeutic intervention;novel therapeutics;Online Mendelian Inheritance In Man;Pathologic;Pathology;patient derived induced pluripotent stem cells;Patients;Phenotype;Process;programs;Proliferating;Protein Binding Domain;protein biomarkers;Proteins;Quality of life;SAM Domain;SHFM1 gene;single-cell RNA sequencing;Skin;Skin Manifestations;Stains;supply chain;Syndrome;System;Testing;Therapeutic;Tissues;transcription factor;Variant;Work

PROJECT_TITLE: Effects of TP63 mutations on keratinocyte adhesion and differentiation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10B-C (20)]


NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Caregiving Research;Clinical Research;Disability Research;Heart Disease;Neurosciences;Pediatric

ORG_CITY: BALTIMORE

ORG_NAME: HUGO W. MOSER RES INST KENNEDY KRIEGER

PHR: Project Narrative Children who experience out-of-hospital cardiac arrest (OHCA) are at high risk for difficulties with daily functioning skills, and their caregivers experience a lot of burden. This is an ancillary grant proposal for the funded Pediatric Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (P-ICECAP). The goal is to extend the follow-up period of children enrolled in P-ICECAP from the planned 1-year follow-up for up to an additional 3 years in order to learn more about later changes in function and what helps children and families continue to make gains in the years after OHCA.

PI_NAMEs: SLOMINE, BETH S;SUSKAUER, STACY JENNIFER MARCUS (contact)

PROGRAM_OFFICER_NAME: HARDY, KRISTINA KOREN

PROJECT_TERMS: 3 year old;6 year old;Acceleration;Adaptive Behaviors;Address;Age;Ancillary Study;Applications Grants;Brain Injuries;Caregiver Burden;caregiver stress;Caregivers;Characteristics;Child;Child Health;Childhood;Clinical;Clinical Trials;Cluster Analysis;Cognitive;cognitive skill;cohort;Collaborations;Communication;daily functioning;Data;Deceleration;design;Development;disability;Electronics;Enrollment;Equipment and supply inventories;Evaluation;expectation;experience;Failure;Family;family burden;follow-up;Funding;Future;Goals;health care delivery;Healthcare;Heart Arrest;high risk;Hospitals;Hour;Hypoxic-Ischemic Brain Injury;Impairment;improved;improved outcome;innovation;Intervention;Intervention Trial;Knowledge;Learning;Longitudinal Studies;Longterm Follow-up;Maintenance;Multi-Institutional Clinical Trial;National Heart, Lung, and Blood Institute;National Institute of Neurological Disorders and Stroke;natural hypothermia;neurobehavioral;Neurocognitive Deficit;Neuropsychology;Only Child;out-of-hospital cardiac arrest;Outcome;Outcome Assessment;Outcome Study;Participant;Patients;peer;Performance;protective factors;Quality of life;recruit;Reporting;Risk;Sampling;School-Age Population;Severities;shared decision making;Site;skills;sociodemographic factors;Subgroup;Surveys;survival outcome;Survivors;Telephone Interviews;Time;United States National Institutes of Health;virtual

PROJECT_TITLE: P-ICECAP Extended

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 HSS-B (90)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Biotechnology;Contraception/Reproduction;Cystic Fibrosis;Infertility;Lung;Orphan Drug;Prevention;Rare Diseases;Women's Health Research

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it seeks to develops non-hormonal birth control directed at an ion channel in the cervix. Ion channels regulate the characteristics of mucus secreted from the body, producing mucus that can keep sperm out or allow sperm to pass through and fertilize the egg. This research would support the NICHD's mission of ensuring every person is born healthy and wanted.

PI_NAMEs: HAN, LEO LIU (contact)

PROGRAM_OFFICER_NAME: ALLEN, CATHERINE LEIGH

PROJECT_TERMS: absorption;Affect;analog;Animal Model;Apical;Appearance;Artificial Insemination;Atopobium vaginae;Bicarbonates;birth control;Bodily secretions;Bypass;Cell Culture Techniques;Cell model;Cells;Cervical;Cervix Mucus;Cervix Uteri;Characteristics;Chlorides;Clinical;Clinical Research;Code;Collaborations;Contraceptive Agents;Contraceptive methods;Cyclic AMP;Cystic Fibrosis;Cystic Fibrosis Transmembrane Conductance Regulator;Data;Development;Disease;Drug Delivery Systems;Drug Kinetics;early phase clinical trial;efficacy outcomes;efficacy study;efficacy validation;Endocervix;Endometrium;Ensure;Epithelial Cells;Epithelium;Estradiol;Evaluation;experience;experimental study;female reproductive tract;Fertility;Formulation;Functional disorder;Gel;Grant;Health;Hereditary Disease;high throughput screening;Histology;Hormonal;Human;Hydration status;Hydrogels;Impairment;In Vitro;in vitro activity;in vivo;in vivo evaluation;Infertility;inhibitor;Intestines;Intracellular Transport;intrauterine insemination;Intravaginal Administration;Ion Channel;Ion Exchange;Ions;Kidney;Lead;lead candidate;Levonorgestrel;Liquid substance;Liver;Lung;Measures;Membrane Proteins;Menstrual cycle;Methods;Mission;Modeling;Mucous body substance;Mucous Membrane;Mus;Mutation;National Institute of Child Health and Human Development;nonhuman primate;Nose;novel;novel strategies;Obstruction;Organ;Ovulation;Pancreas;Papio;Papio hamadryas;Penetration;permissiveness;Persons;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Pharmacologic Substance;Phase;physical property;Plasma;Play;preclinical evaluation;pregnant;Primates;Process;Progesterone;Progestins;protein function;Public Health;Rattus;Regulation;Regulator Genes;reproductive tract;Research;response;Rodent;Role;Safety;Salivary Glands;Serum;small molecule;Solubility;sperm cell;Sperm Penetration;Sperm Transport;Structure;Surface;System;targeted delivery;Techniques;Testing;Thick;Tissues;Toxicology;translational model;Universities;Vagina;Vaginal delivery procedure;Vaginal Ring;Vaginal Route of Drug Administration;Vas deferens structure;Viscosity;Water;Woman;women's clinical trial;women's diagnosis;zygote

PROJECT_TITLE: Inhibiting the cystic fibrosis transmembrane conductance regulator (CFTR) in the cervix as a novel approach to non-hormonal contraception

STUDY_SECTION_NAME: Special Emphasis Panel[ZHD1 DSR-Z (55)]


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

ORG_CITY: GALVESTON

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: OVERALL CENTER PROJECT NARRATIVE To improve clinical translational research in a highly vulnerable population (pregnant women and fetuses), we will use our five distinct humanized feto-maternal interface organs on a chip (Microphysiologic systems [MPS]) that uses cells from pregnancy to test its utility in preclinical drug trials. We will test the repurposing of 4 FDA- approved drugs during pregnancy by testing their kinetics, metabolism, and toxicity at the feto-maternal interface. Further, these devices and cells will undergo a qualification process to determine their translational properties by closely engaging with the pharmaceutical industry end-users and submitting the data to the FDA.

PI_NAMEs: HAN, ARUM ;MENON, RAMKUMAR  (contact);RUSYN, IVAN

PROGRAM_OFFICER_NAME: HARGROVE, PASSLEY R

PROJECT_TERMS: 37 weeks gestation;Address;adverse pregnancy outcome;animal data;Animal Model;Area;Biological Markers;Biological Models;Biological Products;Birth;Cell Line;cell type;Cells;Cervix Uteri;Characteristics;Chemical Industry;clinical translation;Clinical Trials;commercialization;Complex;cytotoxicity;Data;Data Management Resources;data submission;Database Management Systems;Decidua;Decision Making;Deposition;Development;Devices;Disease;drug development;Drug Industry;Drug Kinetics;drug repurposing;drug resource;drug testing;Drug Transport;Drug usage;Educational workshop;Elements;Evaluation;Exclusion;experience;fabrication;Face;fascinate;FDA approved;fetal;Fetal Development;Fetal Growth;Fetal Membranes;Fetus;Future;Gestational Diabetes;health application;Human;human model;improved;in utero;In Vitro;Industry;innovation;interest;Intervention Studies;Intrauterine Devices;Kinetics;Lead;manufacturing scale-up;Mediating;Medical;medical complication;medication safety;Membrane;Metabolic;Metabolism;Methods;microphysiology system;model development;Modeling;Mothers;myometrium;nanoscale;National Center for Advancing Translational Sciences;National Institute of Child Health and Human Development;Neonatal Mortality;nonhuman primate;novel strategies;novel therapeutics;organ on a chip;Perfusion;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetic model;pharmacokinetics and pharmacodynamics;Physiological;Placenta;Population;pre-clinical;Pre-Clinical Model;Pre-Eclampsia;Pregnancy;pregnant;Pregnant Uterus;Pregnant Women;Premature Birth;Premature Labor;prevent;Process;Program Description;programs;Property;Protocols documentation;Publishing;Qualifying;quality assurance;Quality Control;recruit;Reporting;Reproducibility;Reproductive Biology;research and development;Resources;response;Risk Reduction;Rodent;Safety;Science;Small for Gestational Age Infant;small molecule;Survivors;System;Technology;Technology Transfer;Teratogens;Testing;Texas;Therapeutic;Therapeutic Research;Time;Tissue Microarray;Tissues;tool;tool development;Toxic effect;Toxicology;Translating;Translational Research;United States;Universities;Uterine Diseases;Uterus;Vulnerable Populations;Woman;Women's Health

PROJECT_TITLE: A Translational Center for Microphysiological Systems-Based Drug Development Tools for Pregnancy and Women's Health

STUDY_SECTION_NAME: Special Emphasis Panel[ZTR1 TC-9 (01)]


NIH_SPENDING_CATS: Women's Health Research

PI_NAMEs: MENON, RAMKUMAR  (contact)

PROJECT_TERMS: Acceleration;Adoption;Analytical Chemistry;Arum;Biochemical;Calibration;Cells;Chemicals;clinical development;clinically relevant;Collaborations;college;commercialization;Communication;Computer Models;Consultations;Cosmetics;Data;Data Management Resources;data quality;data sharing;Database Management Systems;Decision Making;Development;Devices;Discipline;Discipline of obstetrics;Division of Basic Sciences;drug development;Drug Industry;Educational workshop;effectiveness evaluation;Elements;Ensure;Evaluation;experience;experimental study;Faculty;FAIR principles;Feedback;follow-up;Frequencies;fundamental research;Funding;Goals;Government Agencies;Gynecology;Human;human female;Human Resources;Individual;Industry;industry partner;Institution;Joints;Knowledge;Laboratories;Leadership;manufacture;Measurement;Medical;meetings;member;Mentors;microphysiology system;Molecular;Monitor;outreach;Performance;Pharmacologic Substance;practical application;Pregnancy;Preparation;Principal Investigator;Private Sector;programs;prospective;Protocols documentation;Publications;Qualifying;quality assurance;Quality Control;Reporting;Reproducibility;reproductive organ;Research;Research Personnel;Resources;Science;success;technology platform;Technology Transfer;Testing;Texas;Tissue Microarray;Tissues;tool development;Training;Translating;translational potential;Translational Research;Translations;United States National Institutes of Health;Universities;Women's Health;Work

PROJECT_TITLE: Administrative Core


PROJECT_TERMS: Academia;Acceleration;Address;adverse pregnancy outcome;Animal Model;Animals;Benchmarking;biobank;Biological Models;Body System;Cell Line;Cell Maintenance;Cell Separation;cell type;Cells;Cervix Uteri;Characteristics;Clinical;Clinical Trials;Collaborations;commercialization;Complex;cytotoxicity;Data;Decidua;Defect;Devices;drug candidate;drug development;Drug Industry;Drug Kinetics;drug testing;Drug usage;Endothelium;Ensure;Environment;experience;fabrication;female reproductive system;Fetal Membranes;Fetus;Future;Goals;human data;Individual;Industry;interest;Intervention;Laboratories;Metabolic;Metabolism;Methods;Microfabrication;microphysiology system;Modeling;Mothers;operation;Organ;organ on a chip;Orphan;Outcome;Pathway interactions;Pharmaceutical Preparations;Pharmacologic Substance;physiologic model;Physiological;Placenta;Population;Preclinical Drug Development;Preclinical Testing;Pregnancy;pregnant;Pregnant Women;Premature Birth;Procedures;Process;Protocols documentation;Provider;Qualifying;Quality Control;Reproducibility;Research;research clinical testing;Research Personnel;Resources;safety testing;Services;System;Testing;Texas;Therapeutic;therapeutic development;Tissues;tool development;Translating;Translational Research;Trust;Universities;Uterus;Vagina;Variant;Vision;Woman;Women's Health;Work

PROJECT_TITLE: Resources Core