ORG_CITY: ANN ARBOR

PHR: PROJECT NARRATIVE Exposure to toxins such as those found in foods and cigarette smoke greatly increase the risk of developing pancreatic cancer through mechanisms that remain unknown. We have found that toxins cause release of the immune cytokine IL22 which can then induce malignant transformation in the pancreas. This research proposal will define the source of IL22 and the target of its activity in the pancreas with the ultimate goal of identifying strategies to block toxin-mediated pancreatic cancer development.

PI_NAMEs: FRANKEL, TIMOTHY LOUIS (contact)

PROJECT_TERMS: agent orange;Aryl Hydrocarbon Receptor;aryl hydrocarbon receptor ligand;Binding;Biological Response Modifiers;Cancer Etiology;Cancerous;carcinogenesis;Cell Communication;Cell Differentiation process;Cells;cellular targeting;Cessation of life;Chemicals;Chronic;chronic pancreatitis;cigarette smoke;Clinical;cytokine;Cytokine Signaling;Data;Development;Diet;Dioxins;Dysplasia;Environmental Exposure;Epithelial Cells;Epithelium;Excision;Exposure to;Fibroblasts;Fibrosis;Food;Gastrointestinal tract structure;Genetically Engineered Mouse;Goals;Growth;Health;Helper-Inducer T-Lymphocyte;Host Defense;Human;human model;Hydrocarbons;Immune;immune activation;immune cell infiltrate;Immune system;in vivo;Incidence;inducible Cre;Inflammation;inhibitor;insight;Interleukin Activation;interleukin-22;Lead;Lesion;Ligands;Link;Lymphoid Cell;Maintenance;Malignant - descriptor;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Mediator;metaplastic cell transformation;Methods;Mus;novel;Organoids;Pancreas;Pancreatectomy;Pancreatic Adenocarcinoma;Pathologic;Physiological;Pollution;Positioning Attribute;prevent;Production;receptor;Receptor Activation;receptor expression;Receptor Signaling;recombinase;Reporter;Reporting;Research Proposals;Risk;Role;sensor;Shapes;Signal Transduction;single-cell RNA sequencing;Sorting;Source;Specimen;Testing;Tetrachlorodibenzodioxin;Therapeutic;tissue repair;Tissues;Toxic Environmental Substances;Toxin;transcription factor;tumor;tumor progression;Tumor-Derived;tumor-immune system interactions;tumorigenesis;United States;Veterans

PROJECT_TITLE: Role of environmental toxins in shaping the tumor immune microenvironment


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: CINCINNATI

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: CINCINNATI VA MEDICAL CENTER RESEARCH

ORG_STATE: OH

PHR: The project investigates the homeostatic loop between tumor suppressing LC3C autophagy and glucose metabolism in clear cell renal cell carcinoma (ccRCC). ccRCC is the most frequent renal cancer where tobacco smoking, age and male gender represent clinically important risk factors. Tobacco smoking is highly relevant for the VA and military populations as 75% military veterans are current or former smokers. Our recent work identified major effects of tobacco smoking reprogramming glucose metabolism in ccRCC. In particular, we found that the activity of malate- aspartate shuttle that controls NAD/NADH ratios in cytosol and mitochondria and regulates export of aspartate from mitochondria is affected by tobacco smoking. Here we will investigate molecular mechanism regulating activity of malate-aspartate shuttle.

PI_NAMEs: CZYZYK-KRZESKA, MARIA F (contact)

PROJECT_TERMS: Affect;Age;Age Years;Amino Acids;Anabolism;antiporter;Aspartate;ATP Synthesis Pathway;Autophagocytosis;Autophagosome;Bioenergetics;C-terminal;cancer cell;caveolin 1;Cell Proliferation;Citric Acid Cycle;Clear cell renal cell carcinoma;Clinical;Co-Immunoprecipitations;Complex;Coupled;Cytoplasm;Cytosol;Data;Databases;Digestion;Elements;Enzymes;Epidemiology;former smoker;Gender;gene repression;Genes;Genetic Transcription;Glucose;glucose metabolism;Glutamates;Glycolysis;Glycolysis Inhibition;Health;Human;Hydroxylation;Incidence;Investigational Therapies;Ions;Life;Light;lysosomal proteins;Maintenance;Malate-Aspartate Shuttle Pathway;Malates;male;Malignant Neoplasms;MAP1 Microtubule-Associated Protein;Mediating;Medical;Membrane;Metabolic;Metabolism;Military Personnel;military veteran;Mitochondria;Modeling;Molecular;NADH;Natural regeneration;new therapeutic target;novel;Oncogenic;Output;oxidation;Oxidation-Reduction;paralogous gene;Pathway interactions;Pentosephosphate Pathway;Pentosephosphates;Peptides;Persons;Population;prevent;Primates;Process;Procollagen-Proline Dioxygenase;Proline;Regulation;Renal Carcinoma;Renal Cell Carcinoma;Risk;Risk Factors;Role;service member;stemness;Testing;therapeutic target;Tobacco smoking behavior;tumor;Tumor Suppressor Proteins;Veterans;Warburg Effect;Work

PROJECT_TITLE: Tumor suppressing pathways in renal cancer


ORG_CITY: RICHMOND

ORG_NAME: VA VETERANS ADMINISTRATION HOSPITAL

ORG_STATE: VA

PHR: A common treatment for severe atherosclerotic cardiovascular disease is endovascular placement of an arterial stent. While stent technology has improved over the years, including the development of drug-eluting stents, failure rates remain high and current technologies are associated with significant challenges. We propose to develop an innovative, paradigm-shifting stent technology that will obviate the need for placement of permanent metal stents in the arterial system for the treatment of severe atherosclerosis. Specifically, we propose to develop a solid biodegradable stent from a liquid drug-eluting polymer by photo-polymerizing the stent in the body using a specially designed triple balloon catheter. This custom-formed stent will prevent thrombosis and restenosis while simultaneously promoting endothelialization and long-term vascular health. Given the burden of atherosclerotic cardiovascular disease in the veteran population, the studies in this proposal will result in a novel technology that will significantly improve veteran health.

PI_NAMEs: HUIZAR, JOSE FRANCISCO (contact)

PROJECT_TERMS: Acute;Adherence;Adhesions;Affect;Area;Arteries;Atherosclerosis;Balloon Angioplasty;biodegradable polymer;biomaterial compatibility;Blood Platelets;Blood Vessels;Cardiac;Cardiovascular Diseases;Catheters;Cause of Death;cell growth;Cells;Chemistry;Citrates;Clinical;common treatment;cost;Custom;Data;design;Developed Countries;Development;diazeniumdiolate;Disease;Drug Delivery Systems;drug development;Drug usage;Elasticity;Endothelial Cells;Endothelium;Engineering;Environment;Failure;Family suidae;FDA approved;flexibility;healing;Health;Hyperplasia;improved;In Situ;In Vitro;in vivo;Individual;Industry;Inflammation;Injury;innovation;Intervention;Legal patent;Liquid substance;Longitudinal Studies;manufacture;Measurable;mechanical properties;Metals;military veteran;Modification;Modulus;multidisciplinary;new technology;Nitric Oxide;Nitric Oxide Donors;novel;novel strategies;Operative Surgical Procedures;Paclitaxel;Patient-Focused Outcomes;Peripheral;Pharmaceutical Preparations;photopolymerization;Polymers;porcine model;preclinical study;prevent;Process;Proliferating;Prosthesis;prototype;Radial;Research Personnel;restenosis;S-Nitrosothiols;Safety;safety study;Secondary to;Sirolimus;Site;Solid;stent thrombosis;Stents;Surface;System;Technology;Testing;thrombogenesis;Thrombosis;Time;Translating;Vasodilation;Vertebral column;Veterans

PROJECT_TITLE: Novel in situ custom biodegradable drug-eluting stents for endovascular surgery


ADMINISTERING_IC: HG

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Contraception/Reproduction;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hematology;Human Genome;Pediatric;Prevention;Rare Diseases;Sickle Cell Disease

ORG_CITY: GAINESVILLE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative Our goal is to foster genetically-informed reproductive health behaviors concordant with informed parenting plans among young adults with sickle cell disease or sickle cell trait, who intend to have a child free of sickle cell disease, but are at risk for their children inheriting the disease. Our intervention is designed to help them understand the inheritance of sickle cell disease and the many ways they can consider to implement their informed parenting plan. If successful, CHOICES could become widely available as a preconception intervention that helps young adults to understand the genetic inheritance of sickle cell disease and ways acceptable to them for reducing the risk of their child inheriting the disease.

PI_NAMEs: KALYANARAMAN, SRIRAM ;WILKIE, DIANA J (contact);YAO, YINGWEI

PROGRAM_OFFICER_NAME: KULCHAK RAHM, ALANNA LEE

PROJECT_TERMS: Adult;Affect;aged;American;Behavior;cell community;Child;Child Rearing;Clinic;Communication;community organizations;comparison control;Conceptions;cost;cost effective;Data Collection;Demographic Factors;design;Disease;Distant;electronic book;follow-up;Fostering;Future;Genes;Genetic;Genetic Counseling;Genetic Diseases;Goals;Health behavior;Health Care Costs;health disparity;health knowledge;healthcare community;Hemoglobin;Individual;Infant;insight;Intention;Intervention;intervention delivery;intervention effect;Knowledge;Measures;Media Intervention;men;Mendelian disorder;Methods;Minority;Modeling;Morbidity - disease rate;mortality;Multimedia;Neonatal Screening;Online Systems;outcome prediction;Participant;Population;Pregnancy;Pregnancy Outcome;pregnant;primary endpoint;Questionnaires;Randomized, Controlled Trials;Readiness;recruit;Regression Analysis;Reporting;Reproducibility;reproductive;Reproductive Behavior;Reproductive Health;reproductive health intervention;Research;Risk;Risk Behaviors;Risk Reduction;Sampling;secondary endpoint;sex;Sickle Cell;Sickle Cell Anemia;Sickle Cell Trait;social media;Specific qualifier value;Subgroup;Technology;Testing;therapy design;Time;Translating;treatment as usual;Woman;young adult

PROJECT_TITLE: CHOICES for Sickle Cell Reproductive Health: RCT of a Preconception Intervention Model for a Single Gene Disorder


ADMINISTERING_IC: MD

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Data Science;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Networking and Information Technology R&D (NITRD);Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: IRVINE

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Narrative  There is a critical need to increase engagement in HIV care among individuals living with HIV/AIDS, especially among Black/African American and Latinx communities. Due to the COVID-19 pandemic, researchers and policymakers have been able to develop new and impactful public-private partnerships, including with digital outreach/marketing companies, to attempt to control the growing COVID-19 pandemic. To our knowledge, this is the first study seeking to apply these recent “big data outreach” methods to the field of HIV, using them to address gaps in identifying and intervening among individuals who are out of HIV care.

PI_NAMEs: YOUNG, SEAN  (contact)

PROGRAM_OFFICER_NAME: STINSON, NATHANIEL

PROJECT_TERMS: Address;Adherence;Adopted;Advertising;Affect;African American;aged;Area;barrier to care;Big Data;Black Populations;Black race;care outcomes;Caring;Case Study;Clinic;cohort;Cohort Studies;Color;Communication;Communities;County;COVID-19 pandemic;COVID-19 risk;Crime;Data;data de-identification;data quality;Data Sources;design;Devices;digital;digital communication;digital data;District of Columbia;Dropout;Enrollment;Epidemic;Epidemiologic Methods;Epidemiology;Ethics;European Union;experience;Facebook;follow-up;Future;Geography;handheld mobile device;Health;Health Insurance Portability and Accountability Act;high risk;HIV;HIV/AIDS;implementation science;improved;Individual;innovation;insight;interactive visualization;Intervention;Interview;Knowledge;Latinx;Latinx population;Laws;Learning;Machine Learning;Maps;Marketing;Mediator;Mental Health;Methods;mobility aid;Modeling;Movement;Neighborhoods;novel;Oranges;Outcome Measure;outreach;Participant;participant enrollment;Pattern;people of color;Persons;Policy Maker;Prevention;Privacy;Process;Public Health;public-private partnership;recruit;Research;Research Personnel;Risk;Sampling;scale up;Services;socioeconomics;stay-at-home order;Structure;success;Surveys;Target Populations;Technology;Time;tool;United States

PROJECT_TITLE: Big Data Digital Outreach and Epidemiology Methods for HIV Care among Communities of Color

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


ADMINISTERING_IC: CA

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: Osteosarcoma is an aggressive cancer of bone that can progress rapidly leading to death due to tumor metastasis or relapse. This proposal will provide new insights into the novel mechanisms of action of the SCF-Skp2 complex in osteosarcoma tumorigenesis. This knowledge may lead to better treatment paradigm not only in bone cancer but also in other cancers requiring Skp2-mediated mechanisms as well.

PI_NAMEs: HOANG, BANG H (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Address;Alanine;Amputation;Animals;Apoptosis;burden of illness;Cell Cycle;Cell Cycle Progression;Cell Line;cell motility;cell type;Cells;Cessation of life;chemotherapy;Childhood;Clinical;clinically relevant;Combined Modality Therapy;Complex;Cullin Proteins;Cyclin-Dependent Kinase Inhibitor;Cytotoxic Chemotherapy;Data;Defect;Disease;Dose Limiting;Embryo;Emerging Technologies;established cell line;F Box Domain;F-Box Proteins;Fibroblasts;Future;Genetic;Genetically Engineered Mouse;Genomics;Goals;Growth;Histologic;immunoregulation;Implant;implantation;improved;innovation;insight;Invaded;Knowledge;Life;Malignant Bone Neoplasm;Malignant neoplasm of pituitary gland;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Metastatic Neoplasm to the Lung;Modeling;Molecular;mouse model;multicatalytic endopeptidase complex;Mus;Neoplasm Metastasis;neoplastic cell;next generation sequencing;novel;novel therapeutics;Oncogenes;Oncogenic;Operative Surgical Procedures;Organoids;Osteoblasts;Osteosarcoma;Outcome;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phenotype;Pituitary Gland;Play;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;Predisposition;Prognosis;Proliferating;prostate carcinogenesis;Proteins;Quantitative Reverse Transcriptase PCR;Randomized;Relapse;Role;screening;side effect;Skp2 Proteins;stemness;Survival Rate;targeted treatment;Testing;Therapeutic;Therapeutic Effect;Threonine;Tissues;TP53 gene;transcriptome;transcriptomics;Translating;translational impact;translational therapeutics;treatment effect;treatment group;Treatment Protocols;Treatment-related toxicity;tumor;tumor growth;tumor progression;Tumor Suppressor Proteins;tumorigenesis;Ubiquitin;Ubiquitination;Western Blotting

PROJECT_TITLE: Leveraging Tumor Suppressor Inactivation for Osteosarcoma Therapy

STUDY_SECTION: SBDD

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


ADMINISTERING_IC: NS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Racial and Ethnic Minority Health Research

ORG_CITY: CORAL GABLES

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

PHR: The University of Miami Department of Neurology, which includes the Pediatric Neurology Division, will continue its service as a clinical trial site in the NeuroNEXT network, contributing high quality data from a diverse population of both adult and pediatric patients with a range of neurological diseases; and continuing to develop our clinical-translational workforce, providing young investigators and research staff with educational, training and career growth opportunities.

PI_NAMEs: BENATAR, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: OHAYON, JOAN M

PROJECT_TERMS: Acceleration;Adult;Aging;Agreement;Applications Grants;Award;Biological Markers;biomarker development;Black Populations;Black race;brain health;career;Caring;Catchment Area;Childhood;Clinic;Clinical;Clinical and Translational Science Awards;clinical center;Clinical Investigator;Clinical Research;clinical translation;Clinical Trials;Clinical Trials Network;Communities;community building;community engagement;Country;Data;Department chair;design;Development;Development Plans;Doctor of Philosophy;Education;Enrollment;ethnic diversity;experience;Faculty;Fellowship;Florida;Funding;Goals;Grant;Growth;Hispanic;Hispanic Populations;Home;Hospitals;Individual;Industry;Infrastructure;Inpatients;Institution;Institutional Review Boards;Investments;Knowledge;Latino;Lead;Leadership;medical schools;member;Mentors;Mentorship;minority engagement;Minority Recruitment;Mission;Modeling;Movement Disorders;Multi-Institutional Clinical Trial;multi-site trial;Multicenter Studies;Multicenter Trials;National Institute of Neurological Disorders and Stroke;nerve injury;Nervous System Disorder;Neurodegenerative Disorders;Neurologic;Neurology;neuroprotection;Neurosciences;Neurosciences Research;novel therapeutics;Nursing Research;operation;organizational structure;Orphan;Outpatients;participant enrollment;Patients;Pediatric Neurology;pediatric patients;Play;Population Heterogeneity;Positioning Attribute;Process;product development;Productivity;programs;Protocols documentation;racial diversity;Rare Diseases;Recording of previous events;recruit;Research;research and development;Research Personnel;Research Training;Resources;Role;Science;Sensory;Services;Site;skills;Societies;sound;success;Training;Training and Education;training opportunity;Translational Research;translational research program;United States National Institutes of Health;Universities;Visit;willingness;working group

PROJECT_TITLE: Clinical Centers for the NINDS NeuroNEXT(Network of Excellence in Neuroscience Clinical Trials) Consortium


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Pediatric;Sleep Research

ORG_CITY: HADLEY

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

ORG_STATE: MA

PHR: PROJECT NARRATIVE Individual differences in infant sleep time and distribution across the day prohibit clear guidelines, yet sleep is the source of parent and family stress and contributes to infant cognitive and physical development. This research will examine, longitudinally, the function of multiple sleep bouts (morning and afternoon naps) in infants across the triphasic to biphasic sleep transition. A better understanding of nap transitions will enhance our basic understanding of early sleep regulation and inform recommendations and decisions about infant sleep.

PI_NAMEs: SPENCER, REBECCA M C (contact)

PROGRAM_OFFICER_NAME: DIXIT, SHILPY

PROJECT_TITLE: Function of biphasic sleep in infants

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Urologic Diseases

ORG_CITY: NEW YORK

ORG_DEPT: UROLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: • Approximately 50% of non-muscle invasive bladder tumors will have a recurrence after  intravesical BCG treatment. • Our preliminary data has shown a possible tumor cell centric mechanism, secretion of cytokines  CXCL 9/10/11, leading to immune dysregulation allowing for tumor cell resistance. • Using spatial transcriptomics and imaging mass cytometry, as outlined in this grant, will allow  for a high-resolution cellular understanding of this tumor micro-environment to help identify  novel mechanisms leading to BCG resistance to BCG.

PI_NAMEs: HOROWITZ, AMIR ;SFAKIANOS, JOHN  (contact)

PROGRAM_OFFICER_NAME: HOWCROFT, THOMAS K

PROJECT_TERMS: Aftercare;Antineoplastic Agents;Architecture;Autologous;Autologous Tumor Cell;Automobile Driving;Bacillus Calmette-Guerin Therapy;Bacteria;BCG Live;Binding;Biological Assay;Bladder Neoplasm;CD8-Positive T-Lymphocytes;Cell Communication;cell killing;cell motility;Cell Physiology;Cell Separation;Cells;chemokine;Complex;Cultured Tumor Cells;CXCL9 gene;CXCR3 gene;cytokine;Cytometry;Data;Disease;Environment;Failure;FDA approved;functional status;Future;Genes;Grant;Hematopoietic;high risk;HLA Antigens;Image;Immune;immune activation;immune checkpoint;immune resistance;Immunotherapeutic agent;improved;In complete remission;In Vitro;Incubated;Infiltration;Inflammatory;innovation;insight;Interferon Type II;intravesical;KLRD1 gene;Link;Major Histocompatibility Complex;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Measures;Mediating;Natural Killer Cells;neoplastic cell;new technology;Newly Diagnosed;non-muscle invasive bladder cancer;novel;paracrine;Pathway interactions;Patients;PD-1 blockade;PD-1 inhibitors;PD-L1 blockade;pembrolizumab;Phenotype;pre-clinical;pressure;Production;programmed cell death ligand 1;programmed cell death protein 1;Proteins;Proteomics;recruit;Recurrence;Recurrent tumor;Refractory;Regulatory T-Lymphocyte;Resistance;resistance mechanism;Resolution;response;Sampling;Signal Transduction;single-cell RNA sequencing;Sorting;spatial relationship;success;System;T cell response;T-Lymphocyte;Testing;Therapeutic;therapy resistant;Tissues;transcriptome sequencing;transcriptomics;Tuberculosis;tumor;tumor diagnosis;tumor growth;Tumor Immunity;tumor microenvironment;Tumor Subtype;Tumor Tissue;Tumor-Associated Process;Tumor-infiltrating immune cells;Up-Regulation

PROJECT_TITLE: Identifying novel resistance mechanisms in non-muscle invasive bladder cancer treated with Bacillus Calmette-Guerin (BCG)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TIO-D(01)Q]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Genetics;Regenerative Medicine

ORG_CITY: BIRMINGHAM

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative. The experiments described here will address basic mechanisms of development and maintenance in the axial skeleton and provide information necessary for future efforts to developmentally engineer, repair, or regenerate fibrous tissues of the spine, providing relief to those suffering from degenerative disease.

PI_NAMEs: SERRA, ROSA A. (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Address;Affect;Binding Proteins;Biological Assay;Biological Process;Biology;Cell Differentiation process;Cells;Cervical;Chick Embryo;ChIP-seq;Competence;Connective Tissue;Data;Degenerative Disorder;Development;Disease;DNA Binding;Dominant-Negative Mutation;Drug Targeting;Elements;Embryo;Embryonic Development;embryonic stem cell;Engineering;experimental study;Fibrocartilages;Foundations;Future;Genes;Genetic Polymorphism;Genetically Engineered Mouse;Genomics;Growth;Homeostasis;Intervertebral disc structure;Label;Laboratories;Ligaments;Ligands;Maintenance;Maps;Mediating;member;Molecular;Molecular Biology;Motion;mouse model;Movement;mRNA Expression;Mus;Muscle;Mutation;Natural regeneration;Nerve;Pathology;Pathway interactions;Pattern;permissiveness;posterior longitudinal ligament ossification;postnatal;Prevention;Process;Publishing;receptor;regenerative;Regulation;repaired;Response Elements;Role;scleraxis;Sclerotome;scoliosis;Signal Pathway;Signal Transduction;Signaling Protein;skeletal;skeletal tissue;Skeleton;Somites;Spinal Diseases;Spinal Osteophytosis;sternocostal joint;Techniques;Technology;Tendon structure;Testing;TGFB1 gene;TGFB3 gene;TGFBR2 gene;Tissue Engineering;Tissue imaging;Tissues;transcription factor;transcriptome sequencing;Transforming Growth Factor beta;Transgenic Mice;Vertebral column

PROJECT_TITLE: TGFbeta in the pathology and development of the spine

STUDY_SECTION: SBSR

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


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Estrogen;Neurosciences;Stroke;Women's Health Research

ORG_CITY: TUCSON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Our laboratory has uncovered organic anion transporting polypeptide 1a4 (Oatp1a4) as a critical blood-brain barrier (BBB) mechanism that enables 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) to function as effective therapeutics in ischemic stroke. In this proposal, we will study differences in Oatp1a4-mediated transport in male and female animals that are subjected to transient middle cerebral artery occlusion (tMCAO) in order to understand how sex differences can affect statin therapeutic effectiveness in stroke. This work will directly impact public health in the United States by showing how sex as a biological variable must be considered in development of effective neuroprotective treatment strategies for ischemic stroke.

PI_NAMEs: WILLIAMS, ERICA IRIS (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Acute;Affect;Age;age group;Age Years;Alteplase;Animals;atorvastatin;behavior test;Behavioral;Biological;Blood;Blood - brain barrier anatomy;Brain;Brain Ischemia;Cause of Death;Cerebral cortex;Cerebral Infarction;Clinical;Coenzyme A;Cognitive;cognitive performance;Confocal Microscopy;Data;Development;Drug Transport;Edema;Effectiveness;endovascular thrombectomy;experience;experimental study;FDA approved;Female;fexofenadine;Fibrinolytic Agents;Goals;Gonadal Steroid Hormones;Hemorrhage;Hour;improved;In Situ;indexing;inhibitor;Ischemic Stroke;Laboratories;male;Male Castration;Marketing;Measures;Mechanics;Mediating;men;Menopause;Methodology;Methods;Middle Cerebral Artery Occlusion;Modeling;molecular marker;morris water maze;Motor;Neurocognitive;Neurocognitive Deficit;Neurologic;Neurological outcome;neurological recovery;neuroprotection;Neuroprotective Agents;novel;OATP Transporters;object recognition;Operative Surgical Procedures;Organic Anion Transporters;Outcome;Ovariectomy;Oxidoreductase;Performance;Perfusion;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Pharmacotherapy;Phase III Clinical Trials;post stroke;Pravastatin;preclinical study;Property;protective effect;protein expression;Public Health;Rattus;Recovery of Function;Reperfusion Injury;Research Design;Risk;Role;Severities;sex;sex as a biological variable;Sex Differences;Sprague-Dawley Rats;Stroke;stroke incidence;stroke outcome;stroke patient;Stroke prevention;stroke therapy;Testing;Therapeutic;therapeutic effectiveness;therapeutically effective;Time;Tissues;treatment strategy;United States;United States National Institutes of Health;uptake;Variant;Western Blotting;Woman;Work

PROJECT_TITLE: Investigating Oatp-Mediated Delivery of Statins to the Brain in Males and Females: Relevance to Neuroprotective Treatment for Ischemic Stroke


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: MURFREESBORO

ORG_DEPT: BIOLOGY

ORG_NAME: MIDDLE TENNESSEE STATE UNIVERSITY

ORG_STATE: TN

PHR: PROJECT NARRATIVE Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive ovarian malignancy that is driven by absence of a protein called BRG1, which is part of a large protein complex known as the SWI/SNF chromatin remodeling complex. This goal of this project is to test the novel hypothesis that loss of BRG1 results in activation of oncogenic MYC function, which may be in part due to the ability of remaining SWI/SNF subunits to support a pro-tumorigenic gene expression program. Completion of this work will expose how MYC features in these cancers and inform the universal significance of MYC target gene activation seen in several other cancers besides SCCOHT that also have impaired SWI/SNF function.

PI_NAMEs: WEISSMILLER, APRIL M. (contact)

PROGRAM_OFFICER_NAME: SHARMAN, ANU

PROJECT_TERMS: Acute;Affect;Age;ATP phosphohydrolase;Automobile Driving;Binding;Biologic Characteristic;Biological Assay;cancer cell;Cancer cell line;cancer type;Cell Line;Cell Physiology;cell type;chemotherapy;Chromatin;Chromatin Remodeling Factor;Cleavage Under Targets and Release Using Nuclease;Data;Diagnosis;Essential Genes;Exposure to;falls;Gene Activation;Gene Expression;Gene Expression Profile;gene network;Genes;genetic approach;Genetic Transcription;genome-wide;Genomic approach;Goals;Hypercalcemia;Image;Impairment;inducible gene expression;Left;Link;loss of function;Maintenance;Malignant neoplasm of ovary;Malignant Neoplasms;Modeling;Molecular;Mutation;novel;novel therapeutic intervention;Oncogenes;Oncogenic;Oncoproteins;Operative Surgical Procedures;Ovarian;Ovarian Carcinoma;Pathogenesis;Patients;Phenotype;Play;predictive modeling;Process;programs;protein complex;Proteins;Publishing;Recurrence;Recurrent disease;Regulation;Reporting;Residual Cancers;Residual state;Role;Shapes;Small Cell Carcinoma;SMARCA4 gene;SMARCB1 gene;SMARCC1 gene;SWI/SNF Family Complex;Testing;transcription factor;transcriptome;transcriptome sequencing;tumor;Tumor Suppression;Tumor Suppressor Proteins;tumorigenesis;tumorigenic;Woman;Work;young woman

PROJECT_TITLE: Exposing the role of MYC in small cell carcinoma of the ovary hypercalcemic type


FUNDING_MECHANISM: RESEARCH CENTERS

ORG_CITY: SAINT LOUIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: OVERALL PROJECT NARRATIVE Cancer is a complex and heterogenous disease that can arise from somatic and/or germline predispositional events in driver genes/pathways. Because of complex resistance and relapse mechanisms, combination therapies are generally viewed as necessary to improve the outcomes of patients with advanced malignancies. PDX models provide a platform for large-scale testing of combinations, allowing both identification of promising therapeutic regimens for future clinical trials and deeper investigation of the mechanisms governing therapy response and resistance.

PI_NAMEs: DING, LI  (contact);FIELDS, RYAN C;GOVINDAN, RAMASWAMY

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Area;Biodiversity;Bioinformatics;bioinformatics pipeline;Breast;Cancer Center;cancer therapy;Cancer Therapy Evaluation Program;cancer type;candidate identification;capsule;chemotherapy;Clinical;Clinical Data;clinical predictors;Clinical Research;Clinical Trials;Clinical Trials Design;Collaborations;Collection;Colorectal Cancer;combinatorial;Combined Modality Therapy;Complex;Data;Development;Disease;DNA Repair;drug testing;Drug usage;Early Therapeutic-Clinical Trials Network;Engraftment;Ensure;Evaluation;Event;exome sequencing;experience;follow-up;Fostering;Funding;Future;Genes;Genome;Genomics;Germ Lines;Germ-Line Mutation;Goals;Grant;Human;Image;improved;improved outcome;Inflammatory;inhibitor;innovation;Institution;Investigation;KRAS2 gene;Leadership;Malignant Breast Neoplasm;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;medical schools;Metadata;Methods;Modeling;Molecular Target;novel anticancer drug;Participant;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;personalized medicine;Pharmaceutical Preparations;Physicians;Pilot Projects;Pre-Clinical Model;Preclinical Testing;predictive marker;programs;prospective;proteogenomics;Protocols documentation;rare cancer;Recording of previous events;refractory cancer;Regimen;Relapse;Research;Research Infrastructure;Research Personnel;Research Project Grants;Resistance;resistance mechanism;Resource Sharing;Resources;response;Somatic Mutation;Standardization;success;targeted agent;Technology;Testing;Therapeutic;Tissues;transcriptome sequencing;translational impact;Translational Research;Treatment Protocols;treatment response;tumor;Underrepresented Populations;Universities;Validation;Variant;Washington;Work

PROJECT_TITLE: Washington University PDX Development and Trial Center


NIH_SPENDING_CATS: Cancer

PI_NAMEs: DING, LI  (contact)

PROJECT_TERMS: Bioinformatics;Biometry;Budgets;clinical translation;Collaborations;Communication;Contracts;Development;Documentation;Electronics;Funding;Goals;Grant;Group Meetings;Infrastructure;Leadership;Maintenance;medical schools;meetings;Newsletter;outreach;Participant;patient derived xenograft model;Pilot Projects;Preparation;Process;programs;Progress Reports;Publications;Reporting;Research;Research Personnel;Research Project Grants;Resource Sharing;Universities;Washington;web site;working group

PROJECT_TITLE: Admin Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Rare Diseases

PI_NAMEs: FIELDS, RYAN C (contact)

PROJECT_TERMS: Address;Antineoplastic Agents;Authorization documentation;Bioinformatics;Biological Markers;Biological Models;Breast;Cancer Biology;Cancer Model;cancer subtypes;cancer type;Catchment Area;Characteristics;Clinical;Clinical Data;Clinical Oncology;Clinical Research;Clinical Trials;clinically relevant;cohort;Collaborations;Collection;Colorectal;Communities;Comprehensive Cancer Center;Coupled;Data;Databases;Development;Drug Modelings;drug testing;Early Therapeutic-Clinical Trials Network;Ensure;ERBB2 gene;Evaluation;exome sequencing;Feedback;Funding;Genome;genomic profiles;Genomics;Goals;Heterogeneity;Human;improved;Infrastructure;inhibitor;Institution;KRAS2 gene;Link;Lung;Malignant Breast Neoplasm;Malignant neoplasm of gastrointestinal tract;Malignant Neoplasms;medical schools;member;Merkel cell carcinoma;metabolomics;Minority Groups;model development;Modeling;Molecular;Molecular Profiling;Monitor;Mus;mutant;Mutation;Oncology;oncology program;Organoids;Pancreatic Adenocarcinoma;pathogen;patient derived xenograft model;patient oriented;Patients;Procedures;programs;proteogenomics;Proteomics;Quality Control;rare cancer;refractory cancer;repository;Research;Research Personnel;Research Project Grants;Resistance;Resources;Safety;Sampling;Sarcoma;screening;Short Tandem Repeat;Solid Neoplasm;Specimen;Structure;success;synergism;Therapeutic;Tissue Banks;tissue registry;Tissues;tool;transcriptome sequencing;transcriptomics;translational study;triple-negative invasive breast carcinoma;tumor;Underrepresented Minority;Universities;Washington

PROJECT_TITLE: PDX Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Lung;Lung Cancer

ORG_CITY: STANFORD

ORG_DEPT: GENETICS

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Cancer genome sequencing has identified diverse mutations in many oncogenes but there is a general lack of understanding of their differential functions during cancer growth in vivo. Use CRISPR/Cas9- aided homology directed repair and tumor barcoding, we will quantify the impact of overall Kras signaling, PI3K signaling, and Raf/Mek/Erk signaling on the tumorigenic ability of diverse oncogenic Kras variants in mouse lung cancer models. Novel Kras interacting proteins will also be queried for their importance in oncogenic Kras-driven lung cancer.

PI_NAMEs: WINSLOW, MONTE MEIER (contact)

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: Alleles;Area;Bar Codes;Biochemical;Biology;cancer care;cancer genetics;cancer genome;Cancer Model;Cancer Patient;cancer type;carcinogenesis;Cell Culture Techniques;Cell Line;Cessation of life;Chemicals;Clinical;Clinical Trials;Codon Nucleotides;Consumption;Correlative Study;cost;CRISPR/Cas technology;Data;Dedications;Dissection;drug sensitivity;Environment;Epithelial Cells;experimental study;gain of function;Generations;Genetic;genetic approach;Genetically Engineered Mouse;Genome engineering;genome sequencing;Genomics;Genotype;Goals;Growth;Histologic;Human;Impairment;in vivo;KRAS oncogenesis;KRAS2 gene;loss of function;Lung;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Maps;mathematical model;MEKs;Methods;Modeling;Molecular;mouse model;Mus;mutant;Mutate;Mutation;novel;Oncogenes;Oncogenic;overexpression;Pathway interactions;Patients;Pharmacogenomics;pharmacologic;Physiological;PIK3CG gene;Positioning Attribute;Precision cancer therapy;Proteins;PTPN11 gene;repaired;Research;Research Personnel;Signal Pathway;Signal Transduction;Somatic Cell;System;Therapeutic;Therapeutic Uses;Time;tool;tumor;tumor growth;tumorigenic;Variant

PROJECT_TITLE: Genetic dissection of oncogenic Kras signaling

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


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

PROJECT_TERMS: Algorithms;analysis pipeline;anti-cancer research;Bioinformatics;Biometry;Breast;cancer type;Categories;Characteristics;Clinical Data;clinical imaging;Clinical Trials;clinically relevant;Colon;Communities;Complex;Computational Biology;computational pipelines;computational platform;computerized tools;Data;Databases;Development;Drug Combinations;drug repurposing;Drug Targeting;evidence base;experimental study;falls;Fostering;Funding;Future;Genes;Genome;Genomics;Goals;Human;Human Genome Project;Human Resources;improved;in vivo;Informatics;Information Management;Information Systems;Infrastructure;Lung;Metadata;Methods;Modeling;Molecular;multiple omics;Mus;Mutation;neoplasm resource;neoplastic cell;novel;Pancreas;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phenotype;phosphoproteomics;Phosphoric Monoester Hydrolases;Phosphotransferases;Pilot Projects;pre-clinical;preclinical study;Preclinical Testing;preclinical trial;Procedures;programs;proteogenomics;Public Domains;Recommendation;Research;Research Project Grants;Research Support;Residual Neoplasm;Resistance;resistance mechanism;Resources;response;Series;Signal Transduction;software development;software systems;Specificity;Statistical Data Interpretation;The Cancer Genome Atlas;Therapeutic;Time;tool;Translating;treatment response;trial design;tumor;Universities;Washington

PROJECT_TITLE: Bioinformatics Core


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Precision Medicine

PI_NAMEs: CHEN, FENG  (contact)

PROJECT_TERMS: Address;Anatomy;ATAC-seq;Atlases;Bioinformatics;Biological Assay;Biological Markers;biomarker identification;cancer genome;Cells;Characteristics;Clinical;clinical imaging;Complex;cost;Data;Development;DNA;Drug resistance;Effectiveness;Ensure;exome sequencing;Future;Genitourinary system;genome sequencing;Genomics;Goals;Heterogeneity;Human;Image;Immunofluorescence Immunologic;improved;in vivo;Individual;individual response;Infrastructure;Maps;Mission;Modeling;Molecular;molecular imaging;Molecular Profiling;Monitor;multiple omics;neoplastic cell;new technology;Oncogenes;patient derived xenograft model;patient engagement;phosphoproteomics;potential biomarker;pre-clinical;Predictive Value;Procedures;Productivity;programs;Proteins;Proteomics;radiological imaging;Research;Research Design;Research Project Grants;Resistance;Resolution;Resource Sharing;Resources;RNA;Sampling;senescence;Services;single nucleus RNA-sequencing;Speed;Stains;Standardization;stress reduction;Stromal Cells;Structure;Supervision;Surveys;targeted imaging;Technology;Testing;therapy resistant;Tissues;tool;trait;transcriptome;transcriptome sequencing;transcriptomics;Treatment outcome;treatment response;tumor;tumor growth;United States National Institutes of Health;Universities;Validation;Visualization;Washington;Work

PROJECT_TITLE: Shared Resources Core


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

PI_NAMEs: MA, CYNTHIA X (contact)

PROJECT_TERMS: Address;Aftercare;Antibody-drug conjugates;antitumor effect;Apoptosis;Area;Biological Assay;Biological Markers;Biopsy;cancer cell;cancer type;Cell Death;cell killing;chemotherapy;Clinic;Clinical;Clinical Trials;Colorectal Cancer;cytotoxic;Data;design;Development;DNA;DNA Damage;Drug Design;drug testing;ERBB2 gene;exome sequencing;Future;gastroesophageal cancer;homologous recombination deficiency;Immunohistochemistry;improved;In Vitro;in vitro Model;in vivo;inhibitor;Investigation;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;malignant stomach neoplasm;Mass Spectrum Analysis;Modeling;multiple reaction monitoring;Mutation;next generation;Non-Small-Cell Lung Carcinoma;Organoids;Pancreatic Adenocarcinoma;Pathway interactions;patient derived xenograft model;Patient Selection;patient subsets;Patient-derived xenograft models of breast cancer;Pharmaceutical Preparations;phosphoproteomics;Poly(ADP-ribose) Polymerase Inhibitor;predicting response;Proteins;proteogenomics;Proteome;Proteomics;repaired;Research Project Grants;response;response biomarker;Sampling;single nucleus RNA-sequencing;Spatial Distribution;Surface;synergism;Testing;Topoisomerase-I Inhibitor;transcriptome;transcriptome sequencing;Trastuzumab;treatment effect;treatment response;tumor;tumor heterogeneity;Tumor-Derived;Type I DNA Topoisomerases;Universities;uptake;Validation;Washington

PROJECT_TITLE: Research Project 1


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

PI_NAMEs: LIM, KIAN H (contact)

PROJECT_TERMS: 3-Dimensional;Academia;antibody conjugate;autocrine;Autophagocytosis;Benchmarking;Bioinformatics;Biological Markers;Biology;biomarker driven;biomarker identification;Blood;Cancer Model;cancer type;chemotherapy;Clinical;Clinical Trials;Clinical Trials Design;Clinical Trials Network;Collaborations;Colon;Colon Carcinoma;combinatorial;Cytotoxic Chemotherapy;Data;Development;Disease Progression;efficacy evaluation;efficacy testing;Ensure;ERBB2 gene;Exposure to;Funding;Future;Genes;Genomics;Immunohistochemistry;improved;In Vitro;in vivo;Industry;Inflammatory;inhibitor;innovation;Institution;Investigational Therapies;KRAS2 gene;KRASG12D;Letters;Lung;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;MAPKAPK2 gene;MEKs;member;Mitogen-Activated Protein Kinase Inhibitor;Mitogen-Activated Protein Kinases;Modeling;multiple omics;Mus;mutant;Mutation;NF-kappa B;novel;novel strategies;novel therapeutics;objective response rate;Oncogenes;Oncoproteins;Organ;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;Pathway interactions;patient derived xenograft model;Patients;pharmacologic;Phosphotransferases;PIK3CG gene;pre-clinical;preclinical efficacy;Prediction of Response to Therapy;predictive marker;protein kinase inhibitor;Proteomics;Proto-Oncogene Proteins c-akt;receptor;Research Project Grants;Resistance;resistance mechanism;response;Signal Pathway;Signal Transduction;single nucleus RNA-sequencing;spheroids;Stress;success;Surface;systemic toxicity;Testing;Therapeutic;Therapeutic Agents;Tissues;TNF gene;Topoisomerase-I Inhibitor;transcriptomics;Translating;Trastuzumab;treatment response;tumor;tumor growth;Universities;Washington;Work;Xenograft procedure

PROJECT_TITLE: Research Project 2


NIH_SPENDING_CATS: Biotechnology;Cancer

PI_NAMEs: VAN TINE, BRIAN ANDREW (contact)

PROJECT_TERMS: anti-cancer research;Award;Bioinformatics;Cancer Center;Cancer Therapy Evaluation Program;Clinical Trials;Collaborations;Development;Early Therapeutic-Clinical Trials Network;Electronic Mail;Fostering;Funding;Goals;Grant;human disease;innovation;Institution;Life;Mentors;minority investigator;Mission;new technology;Newsletter;patient derived xenograft model;patient subsets;Pilot Projects;pre-clinical;Pre-Clinical Model;Process;programs;recruit;Reproducibility;Research;research and development;Research Methodology;Research Personnel;Research Project Grants;Review Committee;Translating;translational goal;Translational Research;Underrepresented Minority;Universities;Validation;Washington;Woman;Work

PROJECT_TITLE: Pilot Projects and Trans-Network Activities Core


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: JACKSON

ORG_NAME: UNIVERSITY OF MISSISSIPPI MED CTR

ORG_STATE: MS

PHR: Narrative This proposal is to advance the Mississippi Center of Excellence in Perinatal Research (MS CEPR) COBRE at the University of Mississippi Medical Center into Phase 2. Perinatal research encompasses the study of disease states that have their etiology during gestation and early post-natal development that result in long term consequences in the mother and offspring across their lifespans. The long term goal is to develop an nationally recognized, sustainable MS CEPR dedicated to reducing health care disparities and improving the lives of women and their offspring, especially in Mississippi, through discovery, innovation, and translation to prevent and reduce death and disability from perinatally-induced diseases.

PI_NAMEs: RECKELHOFF, JANE F (contact)

PROGRAM_OFFICER_NAME: REVILLEZA, MARIA

PROJECT_TERMS: Acceleration;adult obesity;Aging;Animals;Basic Science;Behavioral;Biomedical Research;Black race;Cardiovascular Diseases;Cardiovascular system;career development;Caucasians;Center for Translational Science Activities;Centers of Research Excellence;Cessation of life;Clinical;clinical center;Clinical Research;Collaborations;confocal imaging;Core Facility;Dedications;Development;developmental disease;disability;Discipline;Disease;disease disparity;disorder risk;Education;Environment;Equipment;Etiology;Extramural Activities;Faculty;Fluorescence-Activated Cell Sorting;Fostering;Funding;Goals;Grant;Health;health care disparity;health disparity;Human;Hypertension;improved;Infrastructure;innovation;interest;International;Kidney;Kidney Diseases;Laboratories;Life;life span;Low Birth Weight Infant;Low Prevalence;Medical center;Mentors;Metabolic;Metabolic Diseases;minority investigator;Mississippi;Mitochondria;Morbidity - disease rate;mortality;Mothers;multidisciplinary;Neurosciences;obesity development;offspring;Peer Review;Perinatal;perinatal environment;Phase;Pilot Projects;Population;population health;Population Research;postnatal development;Pre-Eclampsia;Pregnancy;Pregnancy Outcome;prevent;Productivity;Program Development;programs;Publications;recruit;Research;Research Infrastructure;Research Personnel;Research Project Grants;Research Proposals;Research Support;Scientist;Secure;Services;study population;Translational Research;Translations;Underrepresented Minority;United States;United States National Institutes of Health;Universities;Woman

PROJECT_TITLE: Mississippi Center of Excellence in Perinatal Research, Phase 2


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Clinical Research;Pediatric

PHR: MS CEPR RESEARCH RESOURCES CORE B NARRATIVE The goal of the Research Resources Core B of the Mississippi Center of Excellence in Perinatal Research (MS  CEPR) COBRE in Phase 2 is to continue to provide investigators and trainees with access to state-of-the-art  equipment and technical expertise needed to perform their research. In Phase 2 Core B will include the  following Sub-cores: Animal and Telemetry, Fluorescence-Activated Cell Sorting (FACS), Mitochondrial  Research, Confocal Microscopy, Clinical Research, and Statistical Analyses. The services of Core B are  essential for the successful completion of the studies described in Projects 1-3 and will be an asset to future  RPLs, PPLs, UMMC intramural and extramural faculty.

PROJECT_TERMS: analytical tool;Animals;Biological Assay;Businesses;Cardiorenal syndrome;Cells;Centers of Research Excellence;Charge;Childhood;Clinical;Clinical Research;confocal imaging;Confocal Microscopy;Consent;Data;Dedications;Development;Echocardiography;Equipment;Extramural Activities;Faculty;Fee-for-Service Plans;Flow Cytometry;Fluorescence-Activated Cell Sorting;Fluorescent Dyes;Funding;Genomics;Goals;Gonadal Steroid Hormones;Guidelines;Histology;Human;Human Resources;human subject;improved;Individual;Institutional Review Boards;Laboratories;Maintenance;Mass Spectrum Analysis;Measurement;member;Metabolic Diseases;metabolic phenotype;Methods;Microscope;Mississippi;Mitochondria;Modeling;Neurosciences;participant enrollment;Patients;pediatric department;Perinatal;Phase;Pilot Projects;programs;Reading;recruit;Research;Research Personnel;Research Project Grants;Research Support;Resources;sample collection;Sampling;Scientist;Services;Statistical Data Interpretation;Students;Supervision;Technical Expertise;Telemetry;Training;Universities


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Women's Health Research

PHR: ADMINISTRATIVE, MENTORING AND EDUCATION CORE A Narrative The major goal of the Mississippi Center of Excellence in Perinatal Research (CEPR) is to develop an  innovative, independent and sustainable center of excellence in perinatal research spanning the spectrum from  adverse pregnancy to subsequent outcomes in offspring. Core A will provide administration, fiscal monitoring,  and mentoring of project investigators with the aim to promote their development into NIH-funded investigators.  The Core will administer the Pilot Projects Grant program, and the Mentoring and Education portion of this  Core will provide education in various aspects of research, career development, and provide a process of  formative and summative evaluations of the progress made by research project and pilot project investigators.

PROJECT_TERMS: adverse outcome;Advisory Committees;African American population;Aging;Area;Award;Behavioral;Cardiovascular Diseases;Cardiovascular system;career development;caucasian American;Centers of Research Excellence;Clinical;Collaborations;COVID-19;Department chair;Development;Disease;disease disparity;disorder risk;Education;Effectiveness;Environment;Evaluation;experience;Extramural Activities;Female;fetal;Fostering;Funding;Future;Goals;graduate student;Grant;Health;health disparity;Hypertension;improved;Infrastructure;innovation;Kidney;Kidney Diseases;Lead;Leadership;Life;life span;Light;Low Birth Weight Infant;male;Medical center;meetings;member;Mentors;Mentorship;Metabolic;Metabolic Diseases;minority investigator;Mississippi;Monitor;Morbidity - disease rate;mortality;Mothers;multidisciplinary;National Institute of General Medical Sciences;next generation;Obesity;obesity development;offspring;Outcome;Perinatal;perinatal environment;Phase;Pilot Projects;Policies;Population;Postdoctoral Fellow;postnatal development;Pre-Eclampsia;Pregnancy;Pregnancy Outcome;Premature Labor;Process;Program Research Project Grants;programs;recruit;Reporting;Research;research and development;Research Personnel;Research Project Grants;Resources;Scientist;Training;Underrepresented Minority;United States;United States National Institutes of Health;Universities


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Kidney Disease;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Polycystic Ovary Syndrome (PCOS);Preterm, Low Birth Weight and Health of the Newborn;Women's Health Research

PI_NAMEs: SHAWKY, NOHA  (contact)

PROJECT_TERMS: ACE2;Adult;Adult Children;Adult women;Age;Angiotensin II;Anti-Inflammatory Agents;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cells;clinically relevant;comparison control;cytokine;Dasatinib;Data;Development;Endocrine System Diseases;Female;Human;Hyperandrogenemia;Inflammatory;Infusion procedures;Injury to Kidney;Kidney;kidney cortex;Life;Low Birth Weight Infant;male;Metabolic dysfunction;Mississippi;Modeling;normotensive;offspring;Peptidyl-Dipeptidase A;Perinatal;Phase;Polycystic Ovary Syndrome;Pregnancy;pregnant;Proteinuria;Quercetin;Rattus;receptor expression;Receptor, Angiotensin, Type 1;Refractory;Renal function;Renin-Angiotensin System;Research;response;senescence associated secretory phenotype;senolytics;Sex Differences;Testing;Testosterone;Up-Regulation;Vasoconstrictor Agents;Vasodilator Agents;Woman;young woman


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Contraception/Reproduction;Digestive Diseases;Pediatric;Polycystic Ovary Syndrome (PCOS);Women's Health Research

PI_NAMEs: EDWARDS, KRISTIN SHIREY (contact)

PROJECT_TERMS: Abdominal Pain;Accounting;Affect;Androgens;antioxidant therapy;Antioxidants;associated symptom;Attenuated;blood pressure elevation;Chronic;clinically relevant;Colon;common treatment;comorbidity;Constipation;Data;Development;Diarrhea;Dyslipidemias;Female;gastrointestinal;gastrointestinal symptom;gut dysbiosis;gut inflammation;Hyperandrogenemia;Impairment;improved;Inflammation;Insulin Resistance;Link;Mediating;Metabolic dysfunction;Metformin;Mississippi;Mitochondria;mitochondrial dysfunction;Modeling;Non-Insulin-Dependent Diabetes Mellitus;Obesity;Oxidative Phosphorylation;Patient Noncompliance;Perinatal;Phase;Polycystic Ovary Syndrome;prevent;Rattus;Reactive Oxygen Species;reproductive;Research;Risk;side effect;Testing;United States;Woman


ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: PROJECT NARRATIVE Glioblastoma (GBM) is the most common primary malignant brain tumor, yet through poorly defined mechanisms, GBM is more frequent in males while females experience a survival benefit. As part of this Program Project Grant (P01), we hypothesize that a confluence of sex differences in tumor cells and the microenvironment, emerging from oncogenic events and normal sexual differentiation, underlie mechanistic differences in gliomagenesis and disease outcome. This project is part of our long-term goal to identify sex- specific mechanisms that drive GBM, and can be leveraged for future therapies that move beyond using the same treatments for all GBM patients to tailoring treatment to the unique vulnerabilities of male versus female GBM.

PI_NAMEs: LATHIA, JUSTIN D. (contact)

PROGRAM_OFFICER_NAME: XU, WANPING

PROJECT_TERMS: Address;aggressive therapy;anti-cancer research;Behavior;Bioinformatics;Biometry;Cell Cycle;Cell Cycle Regulation;Cells;chemotherapy;Clinical Trials Design;Development;Disease Outcome;driver mutation;epidemiologic data;Epigenetic Process;Event;experience;Experimental Models;experimental study;Female;Foundations;Four Core Genotypes;Future;Genetic;Genetic Risk;Genomics;Genotoxic Stress;glial activation;Glioblastoma;Glioma;Gliomagenesis;Goals;Growth;Human;Immune;immune activation;Incidence;individualized medicine;innovation;Integrins;Iron;iron metabolism;junctional adhesion molecule;Knockout Mice;Knowledge;LCN2 gene;Macrophage;male;Malignant neoplasm of brain;Malignant Neoplasms;Mediator;Metabolism;Microglia;Modeling;Modification;Molecular;mouse model;multidisciplinary;Mus;neoplastic cell;novel strategies;Oncogenic;Organ;Outcome;Pathway interactions;patient prognosis;Patients;Phenotype;Physiology;Ploidies;Positioning Attribute;Prognosis;Program Research Project Grants;Publishing;Recording of previous events;Reporting;Research Personnel;response;sex;Sex Differences;Sex Differentiation;sexual dimorphism;Signal Transduction;standard of care;Survivors;Testing;translational medicine;Translational Research;treatment response;tumor;tumor growth;tumor microenvironment;tumor progression;Tumor Suppressor Proteins;tumor-immune system interactions;tumorigenic;Woman;women patients;women versus men

PROJECT_TITLE: Sex-based Differences in Glioma


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Genetics;Neurosciences;Rare Diseases;Women's Health Research

PHR: Project Narrative  Glioblastoma (GBM) is the most devastating form of brain cancer and like many other cancers, females are less  likely than males to develop GBM, and, in both children and adults with GBM, outliers for longer survival are  predominantly female. In recently published work, we identified integrin signaling and cell cycle regulation as  determinants of survival in female and male GBM patients, respectively. We predict that understanding how  specific molecular pathways contribute to sex differences in GBM, will reveal novel sex-specific therapeutic  targets that will serve as the foundation for improving survival for all GBM patients through the implementation  of sex-specific approaches to treatment.  !

PI_NAMEs: RUBIN, JOSHUA B (contact)

PROJECT_TERMS: Acute;Address;Adult;American;base;Biology;Cancer Model;Cell Communication;Cell Cycle;Cell Cycle Regulation;Cells;chemotherapy;Child;Chromatin;Chromatin Structure;Clinic;Clinical Trials Design;Coupled;Data;defined contribution;Development;Disease;Electroporation;Enhancers;Epigenetic Process;Exhibits;Female;Fertilization;Foundations;Four Core Genotypes;Gene Expression;Gene Expression Profile;Genes;Genetic;Glioblastoma;Glioma;Gliomagenesis;Goals;Gonadal Steroid Hormones;Guide RNA;health difference;Hormones;improved;improved outcome;in utero;In Vitro;Incidence;innovation;insight;Integrin Signaling Pathway;Integrins;iron metabolism;Laboratories;Life;Macrophage;male;Malignant neoplasm of brain;Malignant Neoplasms;Measures;Mediating;meetings;metaplastic cell transformation;Microglia;Mitotic Checkpoint;Modeling;Molecular;mouse model;multi-scale modeling;Natural Products;neoplastic cell;novel;nuclease;Oncogenes;Other Genetics;Outcome;Pathway interactions;Patient imaging;Patients;Pattern;Phenotype;Ploidies;Positioning Attribute;Predisposition;Publications;Publishing;Regulatory Pathway;response;sex;sex as a biological variable;Sex Chromosomes;Sex Differences;Sex Differentiation;sexual dimorphism;Signal Transduction;standard care;Study models;success;synergism;Testing;Therapeutic;therapeutic target;Time;Tissues;tool;TP53 gene;transcriptome;treatment response;Tumor Suppressor Proteins;tumorigenesis;women patients;Work

PROJECT_TITLE: Project 1:  Sex-specific developmental epigenetics in gliomagenesis


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Estrogen;Genetics;Neurosciences;Nutrition;Rare Diseases;Women's Health Research

PHR: PROJECT NARRATIVE Iron is essential for a multitude of biological processes and in cancer, iron concomitantly drives tumor cell proliferation and immune suppression in the tumor microenvironment. As part of a Program Project grant on sex differences in glioblastoma (GBM), this project will define the mechanisms by which sex-specific microenvironmental interactions, including differences in iron metabolism (tumor and host), microglia, and macrophages, alter the dynamics of GBM growth. This project provides an opportunity to bridge mechanisms by which iron impacts the epigenetic state (Project 1) and microglial and immune cell activation (Project 3).

PI_NAMEs: CONNOR, JAMES ROBERT (contact)

PROJECT_TERMS: Anemia;Astrocytes;Binding;Biological;Biological Availability;Biological Process;biological systems;Breast;cancer cell;Cancer cell line;Cell Culture Techniques;Cell Proliferation;cell transformation;cell type;Cells;Cerebrospinal Fluid;Clinical;Communication;Complement;Complex;Data;dietary;Environmental Risk Factor;Epigenetic Process;epigenetic regulation;Female;Ferritin;Gene Expression;Genetic;glial activation;Glioblastoma;Glioma;Gliomagenesis;Goals;Growth;H ferritin;Human;human model;immune activation;immunocytochemistry;immunological status;Immunosuppression;in vivo Model;Incidence;Inflammation;Intrinsic factor;Iron;iron metabolism;junctional adhesion molecule;Kidney;Knock-out;LCN2 gene;Libido;Link;Liver;Macrophage;male;Malignant Neoplasms;Mediating;metabolic profile;Metabolism;Methods;Microglia;Modeling;Molecular;mouse model;Mus;neoplastic cell;Outcome;Pathway interactions;Patients;Pharmacologic Substance;Positioning Attribute;Prognosis;Program Research Project Grants;programs;Proteins;Publishing;Qualifying;receptor binding;Regulation;Regulator Genes;Resolution;sex;Sex Differences;sexual dimorphism;Signal Transduction;single-cell RNA sequencing;synergism;System;Testing;Therapeutic;transcriptome sequencing;translational potential;tumor;Tumor Burden;tumor growth;tumor microenvironment;tumorigenic;uptake;Woman

PROJECT_TITLE: Project 2: Sexual Dimorphism of Iron Metabolism in GBM


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: OMAHA

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF NEBRASKA MEDICAL CENTER

ORG_STATE: NE

PHR: Narrative The clinical picture of advanced stages of congestive heart failure is often dominated by the presence of enhanced sympatho-excitation, edema and congestion, causing symptoms of dyspnea, fatigue, nausea and discomfort. An impaired ability to excrete a sodium load as well as cardiopulmonary congestion is commonly seen in patients with congestive heart failure. Altered renal function has been suggested to contribute further to progression of the disease. The proposed studies will provide significant new information and insight regarding the use of SGLT2 inhibitors which have been proven to be very beneficial in the treatment of congestive heart failure.

PI_NAMEs: PATEL, KAUSHIK P (contact);ZHENG, HONG

PROGRAM_OFFICER_NAME: KETCHUM, CHRISTIAN J

PROJECT_TERMS: absorption;Address;Adrenergic Receptor;Animals;Attenuated;Canis familiaris;Cardiac;Cardiopulmonary;Cardiorenal syndrome;Cells;Chronic;Clinical;Clinical Research;Congestive Heart Failure;cytokine;Data;Denervation;diabetic patient;Disease Progression;Dyspnea;Edema;Electrophysiology (science);Equilibrium;Event;Excretory function;Fatigue;Feedback;Functional disorder;Glucose;Heart failure;heart function;hemodynamics;Hospitalization;Hyponatremia;immune activation;immune cell infiltrate;Impairment;Inflammation;Inflammatory;inhibitor;insight;Kidney;Liquid substance;Measurement;Mediating;Methodology;Molecular;Molecular Biology Techniques;mortality;Nausea;Nerve;non-diabetic;Norepinephrine;novel;Organ;Patients;Physiological;prevent;Prognosis;Proximal Kidney Tubules;Rattus;Regulation;Renal function;Renal tubule structure;response;Risk;Sodium;Splanchnic Nerves;symporter;Symptoms;System;Testing;Therapeutic;trafficking;Tubular formation;Type 2 diabetic;Water

PROJECT_TITLE: Novel target mechanism (renal nerves) for the beneficial actions of SGLT2 inhibition in congestive heart failure

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TDPS-R(01)]


NIH_SPENDING_CATS: Cancer;Immunotherapy;Urologic Diseases

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: PROJECT NARRATIVE The overall object in the proposed research is to establish a highly effective,biomarker-guided, triple combination therapy for treatment of a large subgroup of patients with a relatively common genotype, which occurs in 25% of bladder cancer. In this genotype, there is a homozygous loss of the methylthioadenosine phosphorylase (MTAP) gene in the chromosome 9p21 region, making these bladder tumors metabolically vulnerable to therapeutic modulation of the tumor immune microenvironment, which would render them sensitive to immune checkpoint therapy. These findings could potentially be extrapolated to other malignancies, as MTAP represents one of the most frequently deleted somatic genes, occurring in 14% of all human cancers.

PI_NAMEs: GAO, JIANJUN  (contact)

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: 9p21;Address;Adenine;Adenosine;biological heterogeneity;Biological Markers;Bladder Carcinoma;Bladder Neoplasm;bladder transitional cell carcinoma;cancer cell;Cancer cell line;Cancer Model;CDKN2A gene;cell killing;Cell Physiology;Cells;Characteristics;checkpoint therapy;chromosome loss;Chromosomes;Clinical;Clinical Data;Clinical Trials;Combined Modality Therapy;cytotoxic;cytotoxicity;Data;Development;Disease;effective therapy;Enzymes;Folic Acid Antagonists;Fostering;Freezing;Genes;genetic signature;Genomics;Genotype;Goals;Human;immune cell infiltrate;Immunologics;Immunotherapy;Impairment;improved;in vivo;inhibitor;Institutional Review Boards;Interferons;knock-down;Knock-out;knockout gene;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Mediating;Metabolic;Molecular;Mus;neoplastic cell;novel;Pathway interactions;patient subsets;Patients;Pemetrexed;Phase II Clinical Trials;Phosphorylases;pre-clinical;programmed cell death ligand 1;programmed cell death protein 1;Pyrimidine;receptor;Reporting;Research;Resistance;resistance mechanism;response;Sampling;Signal Transduction;T-Lymphocyte;Testing;Therapeutic;Tissues;Translations;Treatment Efficacy;tumor;Tumor Tissue;tumor-immune system interactions;Tumor-infiltrating immune cells

PROJECT_TITLE: Effective combination therapy for MTAP-deficient bladder carcinoma by targeting metabolic vulnerability and modulating tumor immune microenvironment

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-M(08)F]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Genetics;Neurosciences;Precision Medicine;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Women's Health Research

PHR: PROJECT NARRATIVE  Cellular interactions between tumor cells and their surrounding microenvironment enhance therapeutic  resistance, the stem cell program, and tumor growth, and we previously identified a cancer stem cell-specific  adhesion mechanism, junctional adhesion molecule-A (JAM-A), that drives glioblastoma (GBM) growth. In this  project, we will focus on the role of JAM-A in the tumor microenvironment, namely microglia, which also  express JAM-A, and test the hypothesis that JAM-A functions as a tumor suppressor in the female  microenvironment. The successful completion of this proposal will demonstrate a sex-specific the role of JAM-  A in the tumor microenvironment, delineate a female-specific signaling axis that suppresses tumor growth,  highlight a sex-specific mechanism of the GBM microenvironment, and integrate with the other projects in this  Program Project application.

PROJECT_TERMS: Acceleration;Adhesions;Advanced Malignant Neoplasm;aggressive therapy;Astrocytes;Attenuated;Brain;brain cell;cancer stem cell;Cell Adhesion;Cell Communication;Cell Maintenance;Cell Physiology;Cell Proliferation;Cells;cellular targeting;chemotherapy;conventional therapy;Data;drug development;Endowment;epidemiology study;Epigenetic Process;experience;Female;Foundations;Four Core Genotypes;Future;Genetic;genetic signature;Genotype;genotypic sex;glial activation;Glioblastoma;Glioma;Goals;granulocyte;Growth;host neoplasm interaction;Human;human tissue;imaging platform;Immune;immune activation;Implant;in vivo;in vivo imaging;Incidence;Individual;Inflammation;Innate Immune Response;insight;interest;Invaded;Iron;iron metabolism;junctional adhesion molecule;Knock-out;Knockout Mice;LCN2 gene;Macrophage;male;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Microglia;Modeling;Molecular;Molecular Target;mouse model;multiphoton microscopy;Mus;Myeloid-derived suppressor cells;Neoplasm Metastasis;neoplastic;neoplastic cell;novel therapeutics;Operative Surgical Procedures;Pathway interactions;Patients;personalized medicine;pharmacologic;Phenotype;Population;precision medicine;Precision therapeutics;Prognosis;programs;Property;Protein Secretion;Radiation therapy;receptor;Reporting;Resistance;Resolution;Role;self-renewal;sex;sex as a biological variable;Sex Differences;sexual dimorphism;Signal Pathway;Signal Transduction;single-cell RNA sequencing;stem cells;synergism;Testing;Therapeutic;therapy resistant;Time;translational goal;Transplant Recipients;tumor;Tumor Cell Invasion;tumor growth;tumor microenvironment;tumor progression;Tumor Promotion;Tumor Suppressor Proteins;tumorigenesis;tumorigenic;uptake;Validation;Wild Type Mouse;Work

PROJECT_TITLE: Project 3:  Sex-specific differences in the tumor microenvironment alter glioblastoma growth


NIH_SPENDING_CATS: Biotechnology;Cancer;Complementary and Integrative Health;Dietary Supplements;Genetics;Immunotherapy;Nutrition;Prevention;Skin Cancer

ORG_DEPT: BIOCHEMISTRY

PHR: PROJECT NARRATIVE  How nutritional interventions affect tumor growth and therapeutic responses are poorly understood. The proposed studies will provide insight into the molecular mechanisms by which glutamine affects melanoma tumor growth and will reveal a novel therapeutic direction to use dietary glutamine supplementation for the prevention of tumor growth and to enhance current therapeutic responses without detrimental side effects.

PI_NAMEs: KONG, MEI  (contact)

PROGRAM_OFFICER_NAME: RISCUTA, GABRIELA

PROJECT_TERMS: Affect;alpha ketoglutarate;Amino Acids;Animals;anti-PD1 antibodies;BRAF gene;cancer cell;Cancer Intervention;Cancer Patient;cancer therapy;Cell Culture System;cell dedifferentiation;Cell Proliferation;ChIP-seq;Citric Acid Cycle;Clinical;Clinical Trials;cofactor;combinatorial;Combined Modality Therapy;comparison control;Data;Development;Diet;dietary;dietary control;Dietary Intervention;Dietary Supplementation;effector T cell;Environment;Epigenetic Process;epigenetic regulation;exhaustion;experimental study;falls;gene network;Glutamine;Goals;histone demethylase;histone methylation;Histones;Hypermethylation;Immune checkpoint inhibitor;Immunocompetent;Immunotherapy;Implant;improved;In Vitro;in vivo;inhibitor;insight;interest;Laboratories;MEKs;Melanoma;Melanoma Cell;Melanoma patient;Melanoma Tumor;Metabolism;metabolomics;Modeling;Modification;Molecular;Monitor;mouse model;Mutate;Neoplasm Metastasis;neoplastic cell;novel therapeutics;Nutritional;Oncogenes;Oncogenic;Oxygen;Pathway interactions;patient derived xenograft model;Patients;PD-1 inhibitors;Play;preclinical study;prevent;Prevention;Prevention therapy;Process;Reporting;Research;Resistance;response;Role;side effect;Solid Neoplasm;Source;Supplementation;T cell response;T-Lymphocyte;targeted treatment;Testing;Time;transcriptome sequencing;treatment response;tumor;tumor growth;tumor metabolism;tumor xenograft;Xenograft procedure

PROJECT_TITLE: Using dietary glutamine supplementation for melanoma prevention and targeted therapy

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Clinical Research;Urologic Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative Benign prostatic hyperplasia (BPH) causes bladder outlet obstruction (BOO) and lower urinary tract dysfunction (LUTD) in elderly men. The intermediate filament proteins overexpression induced contractile dysfunction is associated with increased level of mitochondrial reactive oxygen species in the obstructed bladder. Our proposed experiments will investigate how the reactive oxygen species and these proteins cause BOO/LUTD, and should identify novel targets enabling new strategies and drugs to treat BOO/LUTD.

PI_NAMEs: ETTICKAN, BOOPATHI  (contact)

PROGRAM_OFFICER_NAME: MULLINS, CHRISTOPHER V

PROJECT_TERMS: Address;Adenine Nucleotide Translocase;Age;Animal Model;Benign Prostatic Hypertrophy;Binding;Bladder;Bladder Dysfunction;Carbachol;Cells;Complement;Complex;cost;Data;design;Desmin;Diagnosis;Disease;Elderly man;experimental study;Functional disorder;Future;Generations;genetic approach;Human;improved;in vivo Model;Incidence;Intermediate Filament Proteins;Intermediate Filaments;Knockout Mice;Knowledge;Lower urinary tract;lower urinary tract symptoms;MAPK8 gene;MAPK9 gene;Maps;Measures;Mediating;Mitochondria;mitochondrial creatine kinase;mitochondrial dysfunction;Mitochondrial Proteins;Molecular;Mus;Muscle;muscle hypertrophy;new therapeutic target;novel;Obstruction;Operative Surgical Procedures;Outer Mitochondrial Membrane;overexpression;Oxygen Consumption;Pathogenesis;Patients;Peptides;Pharmaceutical Preparations;Phosphorylation;Population;pressure;Prevalence;Production;Protein Overexpression;Proteins;Reactive Oxygen Species;Rest;Role;Secondary to;side effect;small hairpin RNA;Smooth Muscle;Smooth Muscle Myocytes;Stimulus;Tertiary Protein Structure;Therapeutic;Therapeutic Intervention;therapeutic target;transcriptome;Vimentin;Voltage-Dependent Anion Channel;voltage-dependent anion channel 2

PROJECT_TITLE: Mechanisms of contractile dysfunction in the obstructed bladder: Role of desmin and vimentin

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


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

PROJECT_TERMS: Accounting;Animal Experimentation;Animals;Awareness;Bioinformatics;Biometry;Cancer Biology;Collaborations;Communication;Core Facility;Data;Data Set;Development Plans;Documentation;drug metabolism;Drug Screening;Ensure;Epigenetic Process;experience;Experimental Models;Feedback;Funding;Glioma;Goals;Grant;Human;Human Resources;human subject;Human Subject Research;Individual;innovation;Institution;Iron;Leadership;Manuscripts;meetings;Microglia;Modeling;Monitor;National Cancer Advisory Board;National Cancer Institute;Office of Administrative Management;operation;Oral;Performance;Postdoctoral Fellow;Preparation;Program Research Project Grants;programs;Progress Reports;recruit;Research;Research Personnel;Resources;Schedule;Scientist;Services;Sex Differences;stem;Study Subject;System;Time;Training;tumor microenvironment;Work;Writing

PROJECT_TITLE: Core A:  Administrative Core


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Networking and Information Technology R&D (NITRD);Neurosciences;Rare Diseases

PHR: PROJECT NARRATIVE  The Program Project (P01) Biostatistics/Bioinformatics Core (BBC) will interact with all P01 investigators to  develop and apply appropriate analysis methods and designs to achieve project goals. The Core will work closely  with investigators to ensure that research questions lead to experiments with quantifiable goals and testable  hypotheses. In addition, the Core will provide infrastructure and oversight for secure management of all study  data (whether from publically available resources or generated as part of this P01), working closely with the  Cores to facilitate completeness, accuracy and reproducibility of data for all projects and investigators

PI_NAMEs: LUO, JINGQIN  (contact)

PROJECT_TERMS: Ally;analytical method;Animals;Bioinformatics;Biometry;central database;Clinic;Clinical;Clinical Research;Communication;Comprehensive Cancer Center;Computational Biology;Consultations;Data;Data Analyses;data management;data platform;Data Science;Data Security;Data Set;Database Management Systems;Databases;design;Development;Ensure;Equipment and supply inventories;Experimental Designs;Experimental Models;experimental study;Faculty;Formulation;Foundations;Glioma;Goals;Grant;Hospitals;Human;Human Resources;Informatics;Information Dissemination;Infrastructure;innovation;Institution;Investments;large datasets;Lead;Leadership;Manuscripts;Medical center;Methods;Molecular Profiling;Outcome;Positioning Attribute;programs;Reporting;Reproducibility;Research;Research Design;Research Personnel;Resources;Secure;sex;Sex Differences;single cell sequencing;skills;Specimen;success;The Cancer Genome Atlas;Translational Research;Universities;University Hospitals;Washington;Work;Writing

PROJECT_TITLE: Core B:  Biostatistics/Bioinfomatics Core


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: SALT LAKE CITY

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: The field of neuroimmunology is a rapidly growing discipline at the intersection of immunology and neurosciences. The Neuroimmunology Training Program at the University of Utah is designed to meet this specific need and train future researchers in this clinically relevant field of study.

PI_NAMEs: O'CONNELL, RYAN M (contact);WILCOX, KAREN S

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Neurosciences;Rare Diseases;Women's Health Research

PHR: PROJECT NARRATIVE  The Experimental Models Core is responsible for curation, tracking, quality control, and distribution of all  glioblastoma (GBM) animal models (patient-derived xenograft (PDX) models, PDX-derived organoids, syngeneic  mouse and genetically engineered mice) for experimental studies in all Projects and biospecimens from humans  for validation across multiple institutions. The Core will also be responsible for the generation of organoids from  these models, for two-photon in vivo imaging of tumors in mice, and for single cell and spatial transcriptomics as  technology resources for the P01. A decided benefit of the Experimental Models Core is the coordination and  visibility of shared use of models across all Projects, with shared quality control, batch (or passage) effects,  growth characteristics, genomic profiling, and cross-Project data sharing from the experimental outcomes.

PI_NAMEs: BERENS, MICHAEL E. (contact)

PROJECT_TERMS: Animal Model;Astrocytes;autosome;base;Behavior;biobank;Blood;Brain Neoplasms;cancer imaging;cell transformation;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Characteristics;Clinic;Clinical Data;clinically relevant;Collection;cost effective;Data;data sharing;Databases;DNA;Dominant-Negative Mutation;Electroporation;Engineering;Event;Experimental Models;experimental study;Female;Four Core Genotypes;Freezing;FTH1 gene;Generations;Genes;Genetic;Genetically Engineered Mouse;genomic profiling;Glioblastoma;Glioma;Goals;Gonadal Steroid Hormones;Growth;Guidelines;H ferritin;Heterogeneity;Human;human subject;human tissue;IACUC;imaging platform;Implant;in utero;in vivo;in vivo imaging;in vivo two-photon imaging;Individual;Informatics;Infrastructure;innovation;Institution;Institutional Review Boards;Iron;junctional adhesion molecule;Karyotype determination procedure;Knock-out;Knockout Mice;Label;LCN2 gene;male;model development;Modeling;mouse model;Mus;neoplastic cell;Neurofibromatosis 1;neuropathology;Organoids;Outcome;Paraffin;pathology imaging;patient derived xenograft model;Patients;Performance;Ploidies;Population;Pre-Clinical Model;Preclinical Testing;quality assurance;Quality Control;radiological imaging;Reporter;Research Personnel;Resources;response;Secure;Services;sex;Sex Chromosomes;Sex Differences;Specimen;sry Genes;Standardization;Technology;Testing;Testis;Tissue Banks;tissue fixing;Tissues;TP53 gene;transcriptome sequencing;transcriptomics;Treatment outcome;Tumor Cell Line;tumor microenvironment;two photon microscopy;Universities;University Hospitals;Validation;Xenograft procedure;Y Chromosome

PROJECT_TITLE: Core C:  Experimental Models


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Nutrition;Obesity;Prevention

ORG_CITY: Aurora

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Narrative The proposed research is relevant to public health because it will identify how obesity and weight loss impacts signaling from adipose tissue laced between and within skeletal muscle to alter the risk of type 2 diabetes. These findings will likely provide new therapeutic targets to prevent the age-induced risk of type 2 diabetes. Thus, the proposed research is relevant to the NIH’s mission to enhance health, lengthen life and reduce illness and disability.

PI_NAMEs: BERGMAN, BRYAN C (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Achievement;adipokines;Adipose tissue;Age;Attenuated;Bathing;Biopsy;Body mass index;Body Weight decreased;Clinical;Closure by clamp;combat;cytokine;Data;Development;Diabetes Mellitus;disability;Eicosanoids;Ethnic Origin;experimental study;Extracellular Matrix Proteins;Fibronectins;Future;Glucose Clamp;Health;Human;Hyperinsulinism;improved;In Vitro;Individual;Inflammation;Inflammatory;Inflammatory Response;innovation;Insulin;Insulin Resistance;insulin sensitivity;Intervention;Life;lifestyle intervention;Magnetic Resonance Imaging;Marble;Measures;Metabolic;Metabolic dysfunction;Mission;Muscle;Muscle Fibers;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;Nonesterified Fatty Acids;novel;obese person;Obesity;obesity risk;Outcome;Paracrine Communication;Play;Positioning Attribute;prevent;Public Health;Research;response;Risk;Role;Sampling;sex;Signal Transduction;Signaling Molecule;Skeletal Muscle;Techniques;Testing;therapeutic target;therapy development;Tissues;ultrasound;United States National Institutes of Health;Visceral;weight loss intervention

PROJECT_TITLE: Effect of weight loss on intermuscular adipose tissue (IMAT) signaling

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


NIH_SPENDING_CATS: Autoimmune Disease;Biomedical Imaging;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Heart Disease;Kidney Disease;Nutrition;Obesity;Pediatric;Prevention

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE Advances in continuous glucose monitoring and automated insulin delivery systems have facilitated improved glycemic control, but the residual risk of cardiovascular disease and diabetic kidney disease continues to be high in people with type 1 diabetes, partially ascribed to the obesity and insulin resistance accompanying intensive glycemic therapy. Glucagon-like peptide 1 receptor agonists (GLP-1RA) have been shown to safely lower body mass index, insulin resistance and cardiovascular and diabetic kidney disease risk in people with type 2 diabetes, yet data in type 1 diabetes are lacking. This clinical trial seeks to establish the efficacy of semaglutide, a GLP-1RA, for improving cardiovascular and kidney function, and insulin sensitivity in adults with type 1 diabetes, and to leverage innovate translational methods to define the underlying mechanisms of action.

PI_NAMEs: BJORNSTAD, PETTER ;NADEAU, KRISTEN JANE (contact)

PROGRAM_OFFICER_NAME: REDMOND, NICOLE

PROJECT_TERMS: Adipose tissue;Adult;Age;Agonist;Albumins;Albuminuria;Animal Model;Aorta;arterial stiffness;Attenuated;Biological Availability;Biopsy;Blood Vessels;Body mass index;Body Weight decreased;Cardiac;cardiac magnetic resonance imaging;cardiometabolism;cardioprotection;Cardiopulmonary;Cardiorenal syndrome;Cardiovascular Diseases;cardiovascular disorder risk;Cardiovascular Physiology;Cardiovascular system;Cessation of life;Clinical Trials;Continuous Glucose Monitor;Creatinine;Data;Diabetes Mellitus;Diabetic Ketoacidosis;Diabetic Nephropathy;Disease Outcome;disorder risk;Double-Blind Method;endothelial dysfunction;Endothelium;Event;Fatty acid glycerol esters;Frequencies;Glomerular Filtration Rate;GLP-I receptor;Glucose;Glucose Clamp;glycemic control;Glycocalyx;heart function;hemodynamics;Hyperinsulinism;Hypoglycemia;improved;innovation;insight;Insulin;Insulin Resistance;insulin sensitivity;Insulin-Dependent Diabetes Mellitus;intravital microscopy;Investigation;Iohexol;Kidney;kidney vascular structure;Magnetic Resonance Imaging;Medial;Mediating;Metabolic;Metformin;Methods;Morbidity - disease rate;Myocardial dysfunction;Nitric Oxide;Non-Insulin-Dependent Diabetes Mellitus;NOS3 gene;Obesity;Outcome;Oxidative Stress;Peripheral;Persons;Physiologic pulse;pilot trial;Placebo Control;Placebos;Population;Positioning Attribute;premature;pressure;primary outcome;Randomized;Reactive Oxygen Species;Renal function;Reporting;Residual state;response;Risk;Safety;shear stress;Structure;subcutaneous;System;Thick;Urine;Vascular resistance;Vasodilation;Weight;young adult;Youth

PROJECT_TITLE: Type 1 Diabetes Impacts of Semaglutide on Cardiovascular Outcomes (T1-DISCO)


ADMINISTERING_IC: HD

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

ORG_CITY: ANN ARBOR

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Premature ovarian insufficiency (POI) is a common complication of anticancer treatments, such as chemotherapy and bone marrow transplantation, due to treatment toxicity. In female cancer survivors POI causes sterility, and loss of the ovarian endocrine function, which in turn results in premature osteopenia, muscle wasting, and accelerated cardiovascular disease. In this study we will investigate the capability of encapsulated allogeneic ovarian tissue to initiate physiological puberty in adolescent non-human primates, and the longevity of graft function along with the dynamics of the recipient’s immune response to a single and repeated transplantations.

PI_NAMEs: SHIKANOV, ARIELLA  (contact)

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: Acceleration;Adolescent;Adult;Affect;Allogenic;Allografting;Animal Model;Animals;anti-cancer treatment;Autologous;Autologous Transplantation;Bone Marrow Transplantation;bone quality;cancer cell;cancer recurrence;cancer risk;Cancer Survivor;cancer therapy;capsule;Cardiovascular Diseases;Cell Therapy;chemotherapy;Chemotherapy and/or radiation;Child;Circulation;clinical translation;clinically relevant;cognitive development;Competence;Complication;Cryopreservation;cytotoxic;Data;design;Development;Diabetes Mellitus;Diffusion;Disease remission;efficacy testing;Embryonic Development;Encapsulated;Endocrine;Engineering;Estrogen deficiency;Estrogens;Estrus;ethylene glycol;Event;Exposure to;Face;Female;Female Adolescents;Fertility;Fertilization;Follicle Stimulating Hormone;folliculogenesis;girls;Goals;graft function;Growth;Health;Height;Hematologic Neoplasms;Hormonal;Hormone imbalance;Hormone replacement therapy;Hormones;Human;Hydrogels;Immune;Immune response;Immunity;Immunosuppression;Impairment;Implant;implantation;improved;Intervention;isoimmunity;Life;Longevity;loss of function;Malignant Breast Neoplasm;Malignant Childhood Neoplasm;Metabolic;meter;millimeter;Modernization;mouse model;Mus;Muscular Atrophy;Nature;nonhuman primate;novel;Obesity;oocyte quality;Oocytes;Osteopenia;Outcome;Ovarian;Ovarian hormone;Ovarian Tissue;Ovariectomy;Ovary;ovary transplantation;Patients;Pattern;Periodicity;Physiological;Pilot Projects;Preclinical Testing;premature;prepuberty;prevent;primary ovarian insufficiency;Primates;Progesterone;Puberty;Research;response;restoration;Risk;risk minimization;Rodent;standard of care;Sterility;Stimulus;Survival Rate;Testing;thrombotic;Tissues;tool;translation to humans;translational potential;Transplantation;Treatment-related toxicity;United States;young woman

PROJECT_TITLE: Immuno-Isolating capsule for delivery of cell-based therapy for restoration of ovarian endocrine function in an animal model

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


NIH_SPENDING_CATS: Contraception/Reproduction;Infertility;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE. Successful formation of embryonic and extra-embryonic tissues is a prerequisite for further successful development. The overall aim of this application is to reveal the principles of self-organization that lead to de novo polarization and consequently the first cell fate specification that leads to the segregation of embryonic and extra-embryonic tissues in the key model mammalian embryo, the mouse embryo. These studies will identify mechanisms underlying the very early stages of mouse development and will likely have major medical relevance in the prevention of pregnancy loss in humans.

PI_NAMEs: ZERNICKA-GOETZ, MAGDALENA  (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Acceleration;Actins;Actomyosin;Affect;Apical;Assisted Reproductive Technology;Behavior Control;blastocyst;Cell Cycle;cell fate specification;cell type;Cells;Complex;Cytoskeleton;Data;Defect;Development;Developmental Biology;Dose;Embryo;embryo tissue;Embryonic Development;Embryonic Induction;Ensure;Event;Experimental Models;experimental study;Fetus;GATA3 gene;Genetic Transcription;Goals;Human;Imaging Techniques;implantation;Inner Cell Mass;insight;Link;Mammals;Mediating;Medical;Methods;Modeling;Morphogenesis;mouse development;Mus;Myosin ATPase;natural Blastocyst Implantation;novel;Nuclear Translocation;optogenetics;pharmacologic;Placenta;pluripotency;polarized cell;pregnancy failure;Pregnancy loss;pregnancy prevention;preimplantation;Process;progenitor;programs;Property;protein complex;Proteins;Regenerative Medicine;Reproduction;rho;Role;segregation;self organization;Signal Transduction;Specific qualifier value;stem cell biology;Testing;Time;Totipotency;Totipotent;transcription factor;Up-Regulation;Work;zygote

PROJECT_TITLE: Temporal program for cell fate specification in the mouse embryo

STUDY_SECTION_NAME: Development - 2 Study Section[DEV2]


ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF VIRGINIA

PHR: Project Narrative Abdominal aortic aneurysm (AAA) is the 13th leading cause of death in the United States, yet there are no FDA- approved drugs that can remedy this disease. Surgical repairs remain the only effective option, but are too risky to be applied to early-stage AAAs which account for the majority of the newly diagnosed cases. We have identified an AAA-prompting pathway and conceived an innovative approach to target this pathway precisely at AAA lesions. We expect that our continued research will ultimately lead to the long sought-after pharmacotherapy for millions of at-risk AAA patients.

PI_NAMEs: GONG, SHAOQIN -;GUO, LIANWANG ;KENT, K CRAIG (contact)

PROGRAM_OFFICER_NAME: DANTHI, NARASIMHAN

PROJECT_TERMS: Abdominal Aortic Aneurysm;aging population;Angiotensin II;Aorta;Aortic Aneurysm;Apoptosis;Area;arm;Automobile Driving;biological adaptation to stress;Biomimetics;Blood Platelets;Cause of Death;Chemistry;Clinical;combat;Complex;cost;Cytosol;Data;Death Rate;design;Disease;Drug Delivery Systems;Drug Targeting;effective therapy;Elastases;Elderly;Encapsulated;Endoplasmic Reticulum;endoplasmic reticulum stress;Endosomes;Endothelial Cells;Event;Experimental Models;FDA approved;Formulation;Functional disorder;Genetic;Glutathione;Goals;Growth;Homing;Human;Hydrophobicity;Imidazole;improved;In Vitro;in vivo;Incidence;Inflammation;innovation;Intervention;invention;kinase inhibitor;Knock-out;Lead;Lesion;Life;Macrophage;male;Manuscripts;Mediating;Medical;Membrane;Methods;mitochondrial dysfunction;Modeling;Molecular Target;Morbidity - disease rate;mortality;mortality risk;mouse model;multidisciplinary;multimodality;Mus;nanobomb;nanocluster;nanoparticle;nanosystems;nanotechnology platform;nanotherapy;new therapeutic target;Newly Diagnosed;novel;novel therapeutics;Operative Surgical Procedures;Organ;pancreatic elastase II;paracrine;Pathogenesis;Pathology;Pathway interactions;Patients;Penetration;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phosphotransferases;Pilot Projects;Polyesters;Population;precision drugs;Prevention;protein kinase R;prototype;Publishing;Reactive Oxygen Species;repaired;Reporting;Research;Risk;Role;Rupture;Ruptured Aneurysm;self assembly;sex;Small Interfering RNA;small molecule;small molecule inhibitor;Smooth Muscle Myocytes;success;Symptoms;targeted delivery;targeted treatment;Testing;Therapeutic;Tissues;Translating;United States;Vascular Diseases;vascular inflammation

PROJECT_TITLE: Mechanistic and Translational Determination of PERK-targeting Strategies for Non-surgical Management of Abdominal Aortic Aneurysm

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hypertension;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Disparities in cardiovascular health are a leading cause of morbidity and premature mortality among racially and ethnically minoritized groups and other marginalized populations. A robust evidence base is critical for developing effective interventions to reduce and eliminate health disparities. This methodological project will develop and disseminate statistical methods that support building a robust and generalizable evidence base on key strategies for achieving equity in cardiovascular health.

PI_NAMEs: JACKSON, JOHN WILLIAM (contact)

PROJECT_TERMS: Address;Adoption;Adult;Age;aged;All of Us Research Program;analytical method;Applied Research;Behavior;cardiovascular health;Caring;Clinical;Cluster randomized trial;cohort;Communities;community organizations;comorbidity;Complex;Computer software;Coronary Artery Risk Development in Young Adults Study;Data;Data Set;Data Sources;Decision Making;design;Development;Disparity;disparity reduction;Educational workshop;effective intervention;Elements;Equity;ethnic minority population;Event;evidence base;Exhibits;Face;Feedback;follow-up;Goals;Health;health disparity;health equity;Health equity research;Healthcare Systems;Hypertension;hypertension control;improved;inattention;Inequity;interest;intersectionality;Intervention;intervention effect;Intervention Trial;Life Style;marginalized population;Measures;Mediating;Mediation;medication compliance;method development;Methodology;Methods;Minority Groups;Morbidity - disease rate;multi-component intervention;multiple chronic conditions;novel strategies;Outcome;outcome disparities;patient oriented;Population;Premature Mortality;programs;racial difference;racial disparity;racial health disparity;racial minority population;racial population;Research;Research Personnel;Risk Factors;Sampling;Sampling Studies;sex;simulation;social group;Socioeconomic Status;Software Tools;Statistical Methods;Structure;Subgroup;symposium;therapy design;Time;tool;treatment disparity;trend;web site;Work;Writing

PROJECT_TITLE: Analytic Methods to Inform Interventions that Advance Cardiovascular Health Equity

STUDY_SECTION: ASPB

STUDY_SECTION_NAME: Analytics and Statistics for Population Research Panel B Study Section[ASPB]


NIH_SPENDING_CATS: Autoimmune Disease;Breastfeeding, Lactation and Breast Milk;Crohn's Disease;Digestive Diseases;Inflammatory Bowel Disease;Microbiome;Nutrition;Pediatric;Prevention

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

PHR: Project Narrative  This proposal will elucidate novel mechanisms through which 2'-fucosyllactose, the most abundant oligosaccharide in human milk, preserves intestinal barrier function against injury under inflammatory condition in adulthood, thus these studies have significant relevance to human health by laying a foundation for developing human milk-derive oligosaccharides for adults as a therapy for diseases associated with deteriorating intestinal homeostasis.

PI_NAMEs: YAN, FANG  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Adult;Apoptosis;Attenuated;Bacteria;Basic Science;Bifidobacterium;Biochemistry;Biological Process;Breastfed infant;Cattle;Cells;chemotherapy;Clinical Research;Colitis;commensal bacteria;Complication;Consumption;Crohn's disease;Cytoprotection;Dairying;defined contribution;Deterioration;Development;Disease;Disease Progression;Epidermal Growth Factor Receptor;Epithelial Cells;Epithelium;epithelium regeneration;Equilibrium;Foundations;Functional disorder;Gene Cluster;Growth;gut inflammation;gut microbiota;Health;Health Benefit;Human;Human Milk;Immune response;Immunity;Impairment;in vitro Assay;Individual;infancy;Infant;Infant formula;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Injury;Insulin-Dependent Diabetes Mellitus;intestinal barrier;intestinal epithelium;intestinal homeostasis;intestinal injury;Intestines;Lactobacillus;Mediating;Metabolic Pathway;Metabolism;metabolomics;microbial;Milk;Mucositis;Mucous Membrane;Multiple Organ Failure;Mus;novel;novel strategies;novel therapeutic intervention;Oligosaccharides;Oxidative Stress;Pantothenic Acid;Pathologic;Pathway interactions;Patients;preservation;prevent;Production;programs;protective effect;Receptor Activation;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Resolution;response;Risk Factors;Role;Sepsis;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Supplementation;Testing;therapeutically effective;Tight Junctions;Transactivation;transcriptome sequencing;Ulcerative Colitis;wound healing

PROJECT_TITLE: Mechanisms by which human milk-derived oligosaccharides protect intestinal barrier and attenuate inflammation

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]