ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Gene regulation is fundamental for every aspect of human function, and errors in this process are key drivers for many diseases ranging from developmental disorders to cancer. This project aims to provide a better understanding of gene regulation by elucidating the functions and mechanisms of a newly recognized form of transcriptional assembly. Successful completion of this project would establish a new model of gene control and have the potential to transform how we target gene dysregulation in cancer and other diseases.

PI_NAMEs: WAN, LILING  (contact)

PROGRAM_OFFICER_NAME: PAZIN, MICHAEL J

PROJECT_TERMS: Address;Affinity;biophysical properties;Cancer Biology;Chromatin;Development;developmental disease;Disease;drug discovery;Epigenetic Process;Gene Activation;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Human;human disease;insight;Link;Malignant Neoplasms;Modeling;Molecular;molecular imaging;Mutation;Oncogenic;Physical condensation;Positioning Attribute;Process;programs;Property;Proteins;Research;Series;single molecule;structural biology;System;therapeutic target;tumorigenesis

PROJECT_TITLE: Illuminating transcriptional condensates using an integrated approach


ADMINISTERING_IC: FD

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: ROCKVILLE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: REVERAGEN BIOPHARMA, INC.

ORG_STATE: MD

PHR: Resume Becker dystrophy is a progressive disorder of skeletal muscle and heart that typically leads to progressive disability. The cause of Becker dystrophy is alternations to the DMD gene that lead to biochemical defects of the dystrophin protein in muscle tissues. There are no approved therapies for Becker dystrophy in the US or elsewhere. The proposed research will carry out a clinical trial of vamorolone in Becker dystrophy, with the goal of providing preliminary data on efficacy and safety. The proposed research would enable a future registration trial of vamorolone in Becker dystrophy.

PI_NAMEs: CLEMENS, PAULA R;HOFFMAN, ERIC P. (contact)

PROGRAM_OFFICER_NAME: POKROVNICHKA, ANJELINA

PROJECT_TITLE: Vamorolone trial in Becker muscular dystrophy


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: A significant proportion of Veterans with substance use disorders (SUDs) have co-occurring psychiatric disorders, the combination of which frequently leads to high inpatient service utilization. Homelessness and higher risk for suicide is common among this population. The combination of SUD with co-morbid MH diagnoses warrants innovative treatment approaches that: a) identify and treat patients during their most vulnerable periods; b) leverage technology; c) partner with current VA programs (e.g. Home Telehealth) and operational priorities (i.e., VHA Handbook 1160.06), toward the goal of reducing inpatient admissions, enhancing treatment engagement and reducing SUD. This study investigates the effectiveness of Combined Recovery Program (CRP) for Veterans with SUDs in the inpatient setting and Home Telehealth in the aftercare setting. Outcomes are assessed at 1 and 3-month follow-up using a multi-modal approach. The ultimate goal is to increase outpatient utilization, reduce substance use, and reduce inpatient/ED visits.

PI_NAMEs: SANTA ANA, ELIZABETH J (contact)

PROJECT_TERMS: Address;Admission activity;Aftercare;Age;Alcohols;Ambulatory Care;Area;arm;Behavior;Care given by nurses;Caring;Cellular Phone;Chronic;Communities;community engagement;Community Integration;comorbidity;cost;COVID-19 pandemic;Data;design;Development;Devices;Diagnosis;Drug Use Disorder;Effectiveness;Eligibility Determination;Emergency department visit;Evaluation;Event;Exhibits;follow-up;Frequencies;future implementation;Goals;handbook;Health;health care service;Health Services Accessibility;Health Technology;health training;Healthcare;Healthcare Systems;high risk;Home;Homelessness;hospital readmission;Hospitalization;Hospitals;Housing;housing instability;illicit drug use;Impairment;implementation barriers;implementation evaluation;implementation intervention;improved;innovation;inpatient psychiatric settings;inpatient service;Inpatients;Intervention;Interview;Life;Maintenance;Measures;meetings;Mental disorders;Mental Health;Mental Health Services;Methods;Modeling;Monitor;motivational enhancement therapy;multimodality;Nicotine Dependence;novel;Nurses;Occupational;Outcome;Outcome Assessment;Outpatients;Participant;patient response;Patients;Performance;Phase;Population;preservation;primary outcome;Procedures;Process;programs;Psychiatric therapeutic procedure;Quality of life;Randomized;readmission rates;Recommendation;Recovery;recruit;reduced substance use;Relapse;relative effectiveness;Reporting;Research Personnel;Research Priority;secondary outcome;Self Management;service gap;service utilization;Services;skills;skills training;social;Social Functioning;substance use;Substance Use Disorder;substance use treatment;suicidal;suicidal risk;Technology;telehealth;Training;treatment arm;treatment as usual;treatment effect;Veterans;web app

PROJECT_TITLE: Impact of Combined Recovery Program and Home Telehealth Among Veterans with substance use disorders in the VA Inpatient Setting

STUDY_SECTION_NAME: HSR-4  Mental and Behavioral Health[HSR4]


ED_INST_TYPE: SCHOOLS OF MEDICINE

ORG_CITY: DURHAM

ORG_DEPT: NEUROSURGERY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative The common malignant pediatric brain tumors, high grade glioma, diffuse intrinsic pontine glioma, and recurrent medulloblastoma are frequently incurable. This project proposes a multi-institutional Phase 2 clinical trial of a novel peptide vaccine targeting pp65, a cytomegalovirus antigen found in these tumors but not in adjacent normal brain, to treat malignant pediatric brain tumors. This immunotherapeutic approach has the potential to radically change how these tumors are treated by improving survival and avoiding the toxicity associated with chemotherapy and radiation.

PI_NAMEs: LANDI, DANIEL BRYCE (contact);THOMPSON, ERIC

PROGRAM_OFFICER_NAME: KAPOOR, SHELLY

PROJECT_TITLE: Phase 2 trial of a novel peptide vaccine targeting CMV antigen for newly diagnosed pediatric high grade glioma and diffuse intrinsic pontine glioma and recurrent medulloblastoma


ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

ORG_STATE: PA

PHR: More than 200,000 Veterans are discharged from the hospital to skilled nursing facilities (SNFs) annually, but more than 1 in 4 is readmitted to the hospital from SNF and less than half have returned to the community by 100 days following hospital discharge. Although the intent of SNF care is to allow recuperation and rehabilitation, Veterans who do not successfully recover are commonly placed in institutional long-term care at significant cost to themselves and to the VA, which spends more than $7 billion annually on institutional care. Veterans receive care in SNFs inside and outside the VA with different rates of success in returning them to the community. This project seeks to identify “high-value” SNFs (those that deliver the best rates of returning Veterans to the community for the lowest costs) across VA and non-VA facilities and understand how much “matching” a Veteran with specific needs to specific SNFs improves value. We then use what we have learned to build models for how the VA could create the highest-value SNF network possible.

PI_NAMEs: BURKE, ROBERT EDWARD (contact)

PROJECT_TERMS: Acute;acute care;adverse event risk;adverse outcome;Affect;Age;Algorithms;Area;authority;Big Data;care costs;care episode;care providers;Caring;Characteristics;Communities;Community Healthcare;community living;Contracts;cost;Data;Data Set;Data Sources;Development;Emergency department visit;Engineering;Enrollment;Fee-for-Service Plans;Fees;Geriatrics;Health care facility;health economics;Healthcare;Home;hospital readmission;Hospitalization;Hospitals;human old age (65+);improved;improved outcome;Individual;innovation;insight;Institution;Leadership;Learning;Life;Long-Term Care;Machine Learning;machine learning method;Marketing;Medicaid;Medical;Medicare;Methodology;Methods;military veteran;model building;Modeling;mortality;novel;Nursing Homes;Nursing Staff;operation;Outcome;Patients;point of care;Policies;Population;Positioning Attribute;Process;Provider;Proxy;Publishing;Quality of Care;Queuing Theory;Recording of previous events;Rehabilitation therapy;Risk;Risk Adjustment;risk prediction;Role;Shapes;Site;Skilled Nursing Facilities;success;System;Techniques;tool;Variant;Veterans;Work

PROJECT_TITLE: Improving Post-Acute Care Value for Veterans

STUDY_SECTION_NAME: HSR-6 Aging, Recovery, and Workforce[HSR6]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Mental Health;Mental Illness;Neurosciences;Prevention;Sleep Research;Suicide;Suicide Prevention

ORG_CITY: STANFORD

ORG_DEPT: PSYCHIATRY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Unhealthy sleep patterns contribute to emotional distress by disrupting the brain networks that regulate emotion. We utilize an innovative multimodal neuroimaging approach to determine if a proven sleep intervention alleviates depressive mood symptoms and reduces suicidality by normalizing these networks. The findings will provide a foundation for optimizing sleep interventions, with profound potential impacts on population health.

PI_NAMEs: GOLDSTEIN-PIEKARSKI, ANDREA  (contact)

PROGRAM_OFFICER_NAME: LEITMAN, DAVID ISAAC

PROJECT_TERMS: 2 arm randomized control trial;Accounting;actigraphy;active control;Adult;Aftercare;Amygdaloid structure;Anxiety;arm;Belief;Biological Assay;Brain;Characteristics;Clinical;clinical outcome measures;Clinical Trials;Cognitive Therapy;comorbidity;Depressive disorder;depressive symptoms;Education;efficacious intervention;Electroencephalography;emotion regulation;emotional distress;emotional functioning;Emotions;Enrollment;Equipment and supply inventories;evidence base;Exclusion;Exhibits;experience;Feeling suicidal;Foundations;Functional disorder;Functional Magnetic Resonance Imaging;improved;improvement on sleep;indexing;Individual;innovation;Intervention;Life;Measurement;Measures;Medial;Mediating;Mental Depression;Mindfulness Training;Modification;mood symptom;multimodal neuroimaging;neural;neurobiological mechanism;neuroimaging;neuroregulation;novel;Outcome;outcome prediction;Outcome Study;Participant;Patients;Phase;population health;predictive marker;Prefrontal Cortex;prevent;primary outcome;Protocols documentation;psychosocial;Randomized;reducing suicide;Research;response;response biomarker;restoration;Risk Factors;Role;secondary outcome;Severities;Sleep;Sleep Disorders;Sleep disturbances;sleep health;sleep pattern;Sleeplessness;Specific qualifier value;Stimulus;suicidal;suicidal risk;Suicide;Symptoms;targeted treatment;Testing;Treatment outcome

PROJECT_TITLE: A Novel Use of a Sleep Intervention to Target the Emotion Regulation Brain Network and Treat Depression and Anxiety


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Psychosis;Rehabilitation;Serious Mental Illness

ORG_CITY: ATHENS

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Project Narrative Prior studies have implicated problems with emotion regulation in the emergence of hallucinations and delusions in people diagnosed with psychotic disorders. We are evaluating whether a cognitive training program administered via a mobile app can improve these difficulties with emotion regulation by enhancing brain activation in the prefrontal cortex. If effective, a new, low cost treatment option will be available that can be employed in everyday life via smart phones.

PI_NAMEs: STRAUSS, GREGORY P (contact)

PROGRAM_OFFICER_NAME: TALKOVSKY, ALEXANDER MAXWELL

PROJECT_TERMS: active method;Adherence;Adverse event;Affective;Amygdaloid structure;Attention;Benchmarking;biological adaptation to stress;Brain;Cellular Phone;Clinical;Clinical Treatment;Clinical Trials;Cognition;cognitive capacity;cognitive neuroscience;cognitive process;Cognitive remediation;cognitive training;Computer Models;computerized;Computers;cost;Data;Delusions;design;Development;Diagnosis;Disease susceptibility;Distal;Ecological momentary assessment;Educational Intervention;effective therapy;effectiveness measure;Elements;emotion regulation;Emotional;Emotions;Etiology;functional disability;functional outcomes;Goals;Hallucinations;Healthcare Systems;improved;improved outcome;indexing;Individual;Intervention;Life;Maintenance;Mental disorders;mobile application;Modality;Modeling;Modification;neural;Neurocognition;neuroimaging;neuromechanism;neuropsychiatric disorder;novel;novel strategies;optimal treatments;Outcome;Outpatients;Participant;Patients;Persons;pharmacologic;Phase;Placebo Control;Placebos;poor communities;Population;precision medicine;Prefrontal Cortex;primary outcome;Process;programs;Protocols documentation;Psychoses;psychosocial;Psychotic Disorders;psychotic symptoms;Randomized;Randomized, Controlled Trials;remediation;Research;Resolution;response;secondary outcome;Short-Term Memory;Signal Transduction;Specific qualifier value;Stress;stress reactivity;Symptoms;Techniques;Testing;Therapeutic;therapy design;Time;Training;Training Programs;Treatment Cost;treatment trial;Validation;Visual

PROJECT_TITLE: Cognitive Training for Emotion Regulation in Psychotic Disorders


ADMINISTERING_IC: AI

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Dengue virus non-structural protein 1 (NS1) is a viral toxin that triggers vascular leak, a hallmark of severe disease in infected patients, via endocytosis into endothelial cells. Identification of NS1 receptors mediating endocytosis into endothelial cells would greatly enhance our understanding NS1 pathogenesis, and provide a promising therapeutic target. Here, we will test the capacity of candidate NS1 receptors, beta-2 adrenergic receptor and epidermal growth factor receptor, to facilitate NS1 endothelial cell endocytosis and pathology.

PI_NAMEs: BIERING, SCOTT BENJAMIN (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Address;Adrenergic Receptor;Agonist;beta-2 Adrenergic Receptors;Binding;Biochemistry;Blood;Blood Vessels;California;candidate identification;career;career development;Cells;Cellular biology;Chicago;Clathrin;clinical biomarkers;Complex;Coupled;cytokine release syndrome;Data;Dengue;Dengue Fever;Dengue Infection;Dengue Virus;Development Plans;Diamond;dimer;Disease;Distal;Endocytosis;Endothelial Cells;endothelial dysfunction;Endothelium;Environment;Epidermal Growth Factor Receptor;extracellular;Family;Flaviviridae;Flavivirus;Functional disorder;Future;G-Protein-Coupled Receptors;Glycobiology;Glycocalyx;Goals;graduate student;Growth Factor Receptors;Heparitin Sulfate;Hospitalization;In Vitro;in vivo;in vivo Model;Infection;inhibiting antibody;innate immune mechanisms;Integral Membrane Protein;Integration Host Factors;Intercellular Junctions;Interferons;Investigation;K22 Award;Link;Lipids;live cell imaging;Los Angeles;Matrix Metalloproteinases;Mediating;Medical;Membrane;Membrane Glycoproteins;Mentors;Metalloproteases;Molecular;Molecular Genetics;mosquito-borne;Mus;new therapeutic target;Nipah Virus;Nonstructural Protein;novel;Organ;Outcome;pathogen;Pathogenesis;pathogenic virus;Pathology;Pathway interactions;Patients;PIK3CG gene;Polysaccharides;Postdoctoral Fellow;Productivity;protein protein interaction;protein purification;Proteins;Public Health;receptor;receptor mediated endocytosis;Receptor Protein-Tyrosine Kinases;Reporting;Research;Research Personnel;Research Project Grants;Research Proposals;Role;Serotyping;severe dengue;Severity of illness;Signal Pathway;Signal Transduction;src-Family Kinases;Techniques;Testing;therapeutic target;tissue tropism;Tissues;Toxin;Training;Transactivation;Tropism;undergraduate student;Universities;uptake;Vaccination;Viral;Viral Pathogenesis;Virulence Factors;Virus;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: Elucidating the roles of the beta-2 adrenergic receptor and epidermal growth factor receptor in flavivirus NS1-mediated endothelial dysfunction

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Research Study Section[MID]


ORG_CITY: NEW ORLEANS

ORG_NAME: SOUTHEAST LOUISIANA VETERANS HEALTH CARE

ORG_STATE: LA

PHR: Prostate cancer is the most common cancer among Veterans, contributing ~30% of all new cancer cases diagnosed in Veterans each year. These numbers plainly demonstrate the high relevance of prostate cancer research to the Veterans' health and healthcare. Despite high demand for discovery of new markers distinguishing indolent from aggressive prostate cancer, tests that accurately predict which patients will develop fatal metastatic disease are lacking. This proposal is designed to (i) establish a new biomarker that can prospectively identify patients, including Veterans, with a significantly elevated risk of developing metastatic prostate cancer and (ii) refine a prototype for a genetic test that can be easily implemented in the clinic to screen men, even prior to diagnosis, for a risk of developing aggressive prostate cancer based on their genetic makeup. Positive outcomes of this study would significantly improve Veterans' health and healthcare.

PI_NAMEs: BELANCIO, VICTORIA PEREPELITSA (contact)

PROJECT_TERMS: Age;anti-cancer research;APC gene;APC mutation;Automobile Driving;Biological Assay;Biological Markers;biomarker discovery;Birth;Blood;Blood specimen;Breast Cancer Patient;cancer diagnosis;Cancer Patient;cancer type;Case/Control Studies;Clinic;clinic ready;Clinical Trials;clinically relevant;cohort;Colorectal Cancer;cost;cost effective;Data;Data Set;Defect;design;Detection;detection method;Development;Diagnosis;Disease;Disease Progression;DNA;DNA Damage;DNA Repair Gene;efficacy testing;Elements;Ethnic Origin;Event;Exclusion;Frequencies;Future;Gene Mutation;Genes;Genetic;genetic makeup;Genetic Markers;genetic testing;Genome;genome sequencing;Genomic DNA;Genomic Instability;Genomics;Goals;Health;Healthcare;high risk;human DNA;Human Genome;improved;Indolent;Inflammation;Insertional Mutagenesis;invention;Legal patent;Link;Long Interspersed Elements;Malignant neoplasm of prostate;Malignant Neoplasms;men;Metastatic Prostate Cancer;Methodology;Methods;Mutate;Mutation;New Drug Approvals;novel;novel marker;novel strategies;Outcome;Outcome Study;overtreatment;Patient-Focused Outcomes;Patients;Poly(ADP-ribose) Polymerase Inhibitor;predictive marker;prospective;prospective test;Prostate;prostate cancer progression;Prostate Cancer therapy;prototype;Publishing;Reporting;research clinical testing;Research Design;Retroelements;Retrotransposon;Risk;Risk Assessment;Risk Factors;Sampling;Sequence Deletion;Source;Statistical Data Interpretation;success;targeted sequencing;Testing;Thinking;Time;Tissues;transcriptome sequencing;tumor DNA;tumor progression;Tumor Suppressor Genes;Urology;Veterans;Vision;whole genome;Work

PROJECT_TITLE: Polymorphic L1 transposons as a Genetic Variable   Distinguishing Aggressive from Indolent Prostate Cancer


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: RELEVANCE TO PUBLIC HEALTH Aedes mosquitoes are the primary vectors of the arboviral human pathogens, and the RNA interference pathway is a major pan-antiviral defense system. This proposal will dissect the function of the RNAi pathway in antiviral defense, and assess its suitability for the development of disease control strategies using transgenic mosquitoes.

PI_NAMEs: DIMOPOULOS, GEORGE  (contact);MYLES, KEVIN M

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Address;Aedes;Anti-viral Response;antiviral immunity;Arbovirus Infections;Arboviruses;Area;arthropod-borne;Bioinformatics;Biology;Chikungunya virus;combinatorial;Complement;Culicidae;Dengue Virus;design;Development;Disease Vectors;disorder control;Drosophila melanogaster;Epidemic;Fat Body;Gene Modified;Gene Silencing;Gene Transfer Techniques;Genes;Genetic;Goals;human pathogen;Immune;Immune signaling;Immune system;Immunity;Infection;innate immune pathways;interdisciplinary approach;Knowledge;La Crosse virus;Laboratories;loss of function;Mediating;Methods;Midgut;model organism;Molecular;Molecular Genetics;Molecular Virology;Movement;mutant;Natural Immunity;next generation sequencing;novel;novel strategies;Ovary;overexpression;pathogen;pathogenic virus;Pathway interactions;Population Replacements;Proteins;Public Health;Regulation;Research;Resistance;Resources;response;RNA Interference;RNA Interference Pathway;Role;Salivary Glands;Signal Transduction;Sindbis Virus;Small Interfering RNA;Small RNA;spatiotemporal;Specificity;System;Testing;Tissues;tool;tool development;transgene expression;Transgenic Organisms;transmission process;vector;Vertical Transmission;Viral;viral RNA;Virus;Work;Yellow Fever;Zika Virus

PROJECT_TITLE: Aedes antiviral RNAi pathway

STUDY_SECTION: VB

STUDY_SECTION_NAME: Vector Biology Study Section[VB]


PHR: PROJECT NARRATIVE: Approximately 11% of cancer patients treated by the Veterans Affairs Medical Centers (VAMCs) are colorectal cancer; however, there are very few drugs that have been approved by the FDA to treat advanced colorectal cancer. In this project, we aim to study a non-toxic mechanism to understand the anti-metastatic activity of sulindac with the intent to support a new indication of this FDA approved generic drug in the treatment of metastatic colorectal cancer. The success of this project will endorse an efficacious, safe, and affordable option to benefit the veterans with advanced colorectal cancer, and eventually reduce the pressure on the VAMCs due to the increasing needs for VA health care.

PI_NAMEs: XI, YAGUANG  (contact)

PROJECT_TERMS: Address;adenoma;advanced disease;Animal Model;Antineoplastic Agents;Aspirin;Biogenesis;biomarker validation;Blood specimen;cancer cell;cancer chemoprevention;Cancer Control;Cancer Etiology;Cancer Intervention;Cancer Patient;Cardiovascular system;cell motility;Cessation of life;Characteristics;Clinic;Clinical;Clinical Trials;colon cancer patients;Colorectal;Colorectal Cancer;colorectal cancer metastasis;colorectal cancer prevention;colorectal cancer progression;Data;Development;Disease;Distant;Distant Metastasis;Dose;exosome;Experimental Animal Model;extend lifespan;Familial Adenomatous Polyposis Syndrome;FDA approved;Forms Controls;Future;General Population;Generic Drugs;Genes;Healthcare;Human;implantation;improved;in vivo;Incidence;Individual;innovation;insight;interest;Invaded;Lead;Lesion;Liver;Lung;Malignant Neoplasms;Mediating;Mediator;Medical center;Meta-Analysis;Metastatic Adenocarcinoma;metastatic colorectal;MicroRNAs;Military Personnel;Modeling;Molecular;mortality risk;mouse model;Mus;Neoplasm Metastasis;Non-Steroidal Anti-Inflammatory Agents;novel;Organ;patient derived xenograft model;Patients;peripheral blood;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Physicians;Plasma;Polyps;preclinical study;premalignant;pressure;prevent;Prostaglandin Inhibition;Prostaglandin-Endoperoxide Synthase;Randomized Controlled Clinical Trials;Regulation;Reporting;Resources;Risk;Role;Safety;Sampling;Specimen;success;Sulindac;Survival Rate;System;systemic toxicity;Therapeutic;Time;Tissue Microarray;Tissues;Toxic effect;transcriptome sequencing;Treatment Efficacy;tumor;tumor progression;Tumor Suppressor Proteins;Tumor-Derived;tumorigenesis;United States;United States Department of Veterans Affairs;Veterans;Xenograft Model

PROJECT_TITLE: MiR-17 mediates sulindac anti-metastatic activity in human colorectal cancer


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Cancer;Climate-Related Exposures and Conditions;Clinical Research;Genetics;Prevention;Skin Cancer;Sleep Research;Social Determinants of Health

ORG_CITY: RALEIGH

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: Project Narrative  Disruption of the human circadian clock as a consequence of shift work has negative health outcomes including genotoxic stress, which can lead to cancer. The proposed research will provide a mechanistic understanding of how the circadian clock regulates DNA damage response signaling and how circadian disruption affects genomic stability and environmental carcinogenesis. The proposed work will: 1) ascertain how circadian mechanisms protect against UVB radiation-mediated DNA damage and genomic instability; 2) provide an improved understanding of genomic instability and carcinogenesis outcomes that are associated with circadian disruption; and 3) guide preventive intervention strategies based on knowledge of the mammalian endogenous circadian clock and its regulation of DNA repair processes. The objectives of this project address the NIEHS mission of increasing the understanding of the biological processes that mitigate environmental diseases associated with circadian clock disruption.

PI_NAMEs: GADDAMEEDHI, SHOBHAN  (contact)

PROGRAM_OFFICER_NAME: RAVICHANDRAN, LINGAMANAIDU V

PROJECT_TERMS: Acute;Address;Affect;American;Beta Particle;Biological Process;cancer initiation;cancer risk;cancer type;carcinogenesis;Carcinogenesis Mechanism;carcinogenicity;Carcinogens;Cell Cycle Checkpoint;Cells;Chronic;circadian;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Critical Pathways;Cues;Data;Development;Disease;Disease Outcome;Disease Progression;disorder prevention;DNA Damage;DNA Repair;Ensure;environmental carcinogenesis;Environmental Impact;environmental mutagens;Environmental Risk Factor;epidemiology study;Event;Experimental Models;experimental study;Exposure to;Fibroblasts;Frequencies;Gene Expression;Genes;Genetic;Genome;Genome Stability;Genomic Instability;Genotoxic Stress;Health;Hour;Human;human subject;Impairment;improved;In Vitro;in vivo;in vivo Model;Inbred HRS Mice;Incidence;Individual;Induced Mutation;Inflammation;Inflammatory;Inflammatory Response;insight;Intervention;Knowledge;lifestyle factors;Light;Maintenance;Malignant - descriptor;Malignant Neoplasms;Mediating;Mission;Molecular;mouse model;Mus;National Institute of Environmental Health Sciences;novel;Nucleotide Excision Repair;Observational epidemiology;OGG1 gene;Outcome;Outcome Study;Pathway interactions;patient population;Periodicity;Phase;Predisposition;preservation;Prevention;Prevention strategy;preventive intervention;Process;Punch Biopsy;Regulation;Research;response;Risk;Risk Factors;Role;Rotation;Sampling;Severity of illness;shift work;Signal Transduction;Skin;Skin Cancer;skin cancer prevention;Skin Carcinogenesis;skin disorder;Skin Neoplasms;Sleep disturbances;solar ultraviolet radiation;Study models;Testing;Time;tumor;tumor progression;Ultraviolet B Radiation;UV protection;UVB induced;virtual;Work;XPA gene

PROJECT_TITLE: Circadian clock disruption: A risk factor for environmental carcinogenesis


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: IOWA CITY

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE: This project will develop and optimize novel engineered carbon materials that simultaneously enhance the performance of organohalide-respiring bacteria (OHRB) and sequester other pollutants that are recalcitrant or inhibitory to OHRB. We will provide a new mechanistic understanding of how carbon material properties (e.g., surface charge, redox-active properties) will shape microbial community structure and drive the expression of metabolic functions associated with reductive dehalogenation processes. Therefore, the proposed research is pertinent to the goals of the Superfund Research Program by developing advanced methods to reduce the amount and toxicity of halogenated pollutants in the environment.

PI_NAMEs: MATTES, TIMOTHY E. (contact)

PROGRAM_OFFICER_NAME: HENRY, HEATHER F

PROJECT_TITLE: Elucidating mechanisms for enhanced anaerobic bioremediation in the presence of carbonaceous materials using an integrated material science and molecular microbial ecology approach


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE The proposed research will quantify the developmental neurotoxicity of lower-chlorinated polychlorinated biphenyls (LC-PCBs) found in the human gestational environment and investigate how metabolism by human cytochrome P450 enzymes influences neurotoxic outcomes in experimental animals exposed to LC-PCBs in the maternal diet throughout gestation and lactation. These outcomes are relevant to public health because they will provide data critically needed to assess the risk these emerging environmental contaminants pose to the developing brain and they will provide insights regarding strategies for mitigating this risk in vulnerable human populations. Therefore, the proposed research is pertinent to the part of NIH’s mission that seeks to develop fundamental knowledge about living systems to enhance health and reduce the burden of human disease.

PI_NAMEs: LEHMLER, HANS-JOACHIM ;LEIN, PAMELA J (contact)

PROGRAM_OFFICER_NAME: LAWLER, CINDY P

PROJECT_TERMS: Address;Adolescent;Air;Animal Experiments;Apoptosis;axon growth;Behavior;Brain;Child;Clinical Data;Coculture Techniques;Cognitive;CREB1 gene;CYP2B6 gene;Cytochrome P450;Data;Development;developmental neurotoxicity;dietary;disorder risk;Dose;Engineering;Environment;Environmental Pollutants;Enzymes;Exposure to;Female;Food;gene environment interaction;Genetic Polymorphism;Goals;Growth;Health;Hepatic;Hepatocyte;Heritability;High Risk Woman;Hippocampus;Human;human disease;human tissue;humanized mouse;In Vitro;in vivo;Industrialization;insight;Knockout Mice;Knowledge;Lactation;Light;Link;male;Mediating;Metabolism;Mission;Molecular;Molecular Target;Morphogenesis;morris water maze;mother nutrition;mouse development;mouse model;Mus;Mutation;neural;neurodevelopment;Neurodevelopmental Disorder;Neuroglia;Neurons;neurotoxic;Neurotoxins;novel;object recognition;Organism;Outcome;Outcome Study;oxidation;Oxidative Stress;Parents;pharmacologic;Phosphorylation;pollutant;Polychlorinated Biphenyls;Population;Positioning Attribute;postnatal;Pregnancy;Pregnant Women;Process;Protein Isoforms;Proteins;Public Health;pup;Recombinants;Research;response;Risk;Risk Assessment;risk mitigation;Role;Ryanodine Receptor Calcium Release Channel;Sampling;Serum;Signal Pathway;Signal Transduction;social;Testing;tool;Ultrasonics;United States National Institutes of Health;Vertebral column;vocalization;Water

PROJECT_TITLE: Molecular and Cellular Basis of PCB Developmental Neurotoxicity

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Mental Health;Neurosciences;Physical Injury - Accidents and Adverse Effects;Social Determinants of Health;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Narrative Physical trauma as an outcome of intimate partner violence (IPV) impacts an estimated 10 million people in the United States each year, with up to 90% of women exposed to IPV reporting episodes of abuse with head trauma. Women exposed to IPV are at a high-risk for developing mental illness and impaired cognitive function, which seems to be compounded in those with exposure to head trauma. This proposal aims to investigate the impact exposure to head trauma in IPV has on cognitive, psychological, and neural processes.

PI_NAMEs: ESOPENKO, CARRIE LYNN (contact);HILLARY, FRANK GERARD;LIN, ALEXANDER PETER;WILDE, ELISABETH A

PROGRAM_OFFICER_NAME: UMOH, NSINI ALEASE

PROJECT_TERMS: Acceleration;Affect;Aggressive behavior;Aging;Anoxia;Anterior;Anxiety;Attention;Autopsy;Behavioral;behavioral phenotyping;Blunt Trauma;Brain;Brain Concussion;Brain Injuries;brain volume;Case Study;Choline;Chronic;chronic traumatic encephalopathy;cingulate gyrus;Clinical;Cognitive;cognitive function;cognitive process;cohort;Cohort Studies;Collaborations;comorbidity;Contusions;Coupled;Craniocerebral Trauma;Data;Deceleration;Dementia;Development;early onset;executive function;experience;Exposure to;Face;Female;Frequencies;Genetic;Glutamates;Glutathione;Goals;Grant;Head;head impact;Health;Height;high risk;Hypoxia;Image;Impaired cognition;Impairment;Injury;Interview;intimate partner violence;Life;life span;Link;Literature;Magnetic Resonance Spectroscopy;member;Memory;Mental Depression;Mental disorders;Meta-Analysis;Military Personnel;Moods;myoinositol;Neck;Nervous System Trauma;neural;neuroimaging;Neurologic;Neuropsychology;Outcome;Pathology;Pathway interactions;Patient-Centered Care;Persons;Phenotype;Population;Post-Traumatic Stress Disorders;Prefrontal Cortex;Prevalence;Process;psychiatric comorbidity;psychologic;psychological outcomes;Public Health;Recording of previous events;Recreation;Reporting;Research;resilience;response;Rest;Risk;Role;Sample Size;Sampling;sexual violence;Short-Term Memory;Site;Sports;Structure;Subgroup;Substance Use Disorder;Survivors;symptom cluster;symptomatology;Symptoms;Syndrome;Techniques;Trauma;trauma exposure;Traumatic Brain Injury;United States;Verbal Learning;Violence;virtual;white matter;Woman;Work;working group

PROJECT_TITLE: Identifying the Cognitive, Psychological, and Neuroimaging Signatures of Head Trauma in Female Survivors of Intimate Partner Violence


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Machine Learning and Artificial Intelligence;Major Depressive Disorder;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Neurosciences;Pediatric;Prevention;Serious Mental Illness

ORG_CITY: BELMONT

ORG_NAME: MCLEAN HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The prevalence of depression increases dramatically during adolescence, particularly for females. Using machine learning algorithms, the overarching goal of the project is to identify neural and behavioral markers that – in combination with clinical and demographic characteristics – reliably predict risk of developing depression during adolescence. The ability to prospectively predict depression prior to its initial onset would have important clinical implications for the early identification of – and targeted deployment of interventions for – at-risk youth.

PI_NAMEs: WEBB, CHRISTIAN ANTHONY (contact)

PROGRAM_OFFICER_NAME: KING, ERIN MICHELE

PROJECT_TERMS: Address;Adolescence;Adolescent;Adult;Age;algorithm development;Anhedonia;anxiety symptoms;Behavior;Behavior assessment;behavior measurement;Behavioral;Characteristics;Childhood;Clinical;clinically relevant;Cluster Analysis;cognitive control;cognitive system;Complex;Conflict (Psychology);Control Groups;cost;Data;Depressed mood;depressive symptoms;Development;Diagnosis;Dimensions;Disease;Disease remission;Early identification;Emotional;endophenotype;Epidemiology;Equipment and supply inventories;Evaluation;experience;Female;follow-up;Functional Magnetic Resonance Imaging;Future;Goals;Heterogeneity;indexing;Individual;Intervention;kernel methods;Link;Literature;Machine Learning;machine learning algorithm;machine learning model;Major Depressive Disorder;male;Maps;Measures;Mental Depression;Modeling;National Institute of Mental Health;Negative Valence;neural;neural correlate;Neurobiology;Neurotic Disorders;Online Systems;Onset of illness;Outcome;Parents;Participant;Patient Self-Report;Phase;pleasure;Positive Valence;Predictive Value;Prevalence;prospective;Puberty;Recording of previous events;recruit;Reporting;Research;Research Domain Criteria;Rewards;Risk;Risk Marker;risk prediction;risk prediction model;rumination;Sampling;Sensitivity and Specificity;single episode major depressive disorder;Socioeconomic Status;Strategic Planning;Stress;Subgroup;Surrogate Markers;Symptoms;System;Teenagers;Telephone;Testing;trait;Youth

PROJECT_TITLE: Predicting the onset of depression in at-risk adolescents from endophenotype profiles

STUDY_SECTION: CPDD

STUDY_SECTION_NAME: Child Psychopathology and Developmental Disabilities Study Section[CPDD]


ADMINISTERING_IC: EY

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: EUGENE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF OREGON

ORG_STATE: OR

PHR: PROJECT NARRATIVE  Psychophysical studies show humans perceive low spatial frequency stimuli more quickly than high spatial frequency stimuli, illustrating coarse-to-fine like processing. By studying the neural circuits and mechanisms underlying the development of coarse-to-fine spatial frequency processing in mice, this project will add to our understanding of how functional visual circuits develop through early postnatal life. The results of this project will shed new light on the circuits mediating spatial vision and may be instructive for a complete understanding of developmental diseases such as amblyopia.

PI_NAMEs: SKYBERG, ROLF J (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Adult;Age;Amblyopia;Anesthesia procedures;area striata;Automobile Driving;awake;Behavioral;Birth;Brain region;Cell Nucleus;Cells;Characteristics;Chemicals;Code;Communities;Complex;dark rearing;Darkness;Data;density;Development;developmental disease;Dissection;Dorsal;Environment;Exhibits;experience;experimental study;extracellular;Face;Feedback;Felis catus;Frequencies;Genetic;Germ Cells;Goals;Human;Image;Individual;Lateral Geniculate Body;Lead;Life;Measures;Mediating;Methods;Monkeys;mouse development;Mus;Muscimol;neural;neural circuit;neuromechanism;Neurons;nonhuman primate;novel;Pattern;pharmacologic;Phase;Physiological;Population;postnatal;postnatal development;Preparation;Process;Property;Psychophysics;Research;Research Personnel;Resolution;Resources;response;Role;Scientist;Series;Shapes;spatial vision;statistics;Stimulus;Structure;success;superior colliculus Corpora quadrigemina;Testing;tool;Training;trend;Visual;Visual Pathways;visual processing;visual stimulus;Visual System

PROJECT_TITLE: Development of coarse-to-fine spatial processing throughout the primary visual system


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza

ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Nosocomial infections caused by the emerging multi-drug resistant pathogen Acinetobacter baumannii frequently occur as a result of patient contact with bacteria persisting on hospital surfaces in a desiccated state. This proposal addresses the regulation of the long-term desiccation tolerance of A. baumannii by a conserved Lon protease, as well as the molecular link between desiccation tolerance and virulence in this organism. Results obtained from this research will strengthen our understanding of how A. baumannii causes disease and create a framework for studying how transmission of this and other nosocomial pathogens occurs.

PI_NAMEs: GREEN, ERIN REBECCA (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acinetobacter baumannii;Acinetobacter baumannii pneumonia;Address;Affect;Anatomy;Antibiotic Resistance;Antibiotics;antimicrobial;Bacteria;Biochemical;biological adaptation to stress;Clinical;clinically significant;COVID-19;Critical Illness;Data;Death Rate;Desiccation;Development;Disease;Disease Outbreaks;Dryness;emerging pathogen;Endocarditis;endopeptidase La;Environment;Environmental Impact;environmental stressor;experimental study;Exposure to;extensive drug resistance;Future;gene product;Genes;genetic approach;genetic regulatory protein;genetic selection;Genetic Transcription;genome-wide;Hospitalization;Hospitals;Human Resources;Immune response;implantable device;improved;Infection;insight;Laboratories;Life;Link;Lung;Lung infections;Mediating;Medical Device;Meningitis;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Multi-Drug Resistance;multi-drug resistant pathogen;Mus;Names;Nosocomial Infections;novel;Organism;pathogen;Pathogenesis;pathogenic bacteria;Pathogenicity;Patients;Peptide Hydrolases;Phenotype;Physiology;Play;Pneumonia;pneumonia model;post-doctoral training;Process;Proteins;Proteome;Proteomics;Regulation;Research;Resistance;response;Role;secondary infection;Sepsis;Severities;Stress;Surface;Therapeutic Intervention;Transcriptional Activation;transmission process;transposon sequencing;Urinary tract;Ventilator;ventilator-associated pneumonia;Virulence;Virulent;Water;Work;World Health Organization;wound

PROJECT_TITLE: Elucidating regulatory control of Acinetobacter baumannii persistence and spread


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Epilepsy;Neurodegenerative;Neurosciences

ORG_CITY: ATLANTA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: EMORY UNIVERSITY

PHR: Project Narrative Multiple lines of evidence have demonstrated that a multidimensional inflammatory response ensues after the prolonged seizures of status epilepticus. We have recently provided evidence that peripheral monocyte infiltration into the brain also mediates an important role, whereby blocking monocyte invasion attenuates neuroinflammation, reduces neuronal injury, prevents erosion of the blood-brain barrier, and enhances weight regain. The current interdisciplinary studies seek to determine if brain-infiltrating monocytes exacerbate a pro- inflammatory response in microglia, pharmacological inhibition of monocyte brain entry also provides beneficial outcomes, and ask if monocytes hasten behavioral decline and promote epileptogenesis.

PI_NAMEs: VARVEL, NICHOLAS  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Address;Adverse effects;Affect;Albumins;Amygdaloid structure;antagonist;Antiepileptogenic;Anxiety;Astrocytosis;Attenuated;attenuation;Behavior;Behavioral;Blood - brain barrier anatomy;Brain;Brain Diseases;brain tissue;Candidate Disease Gene;candidate identification;Cell Physiology;Cells;Cellular biology;Clinical Trials;Cognitive deficits;comorbidity;conditional knockout;design;Deterioration;Development;Dimensions;Disease;Electroencephalography;Encephalitis;Endothelium;Engraftment;Enterobacteria phage P1 Cre recombinase;Epilepsy;Epileptogenesis;Event;Extravasation;Fluorescein-5-isothiocyanate;Frequencies;Future;Gene Expression Profiling;Glean;glial activation;Immune;Immune system;immunoreaction;Impaired cognition;In Vitro;in vivo;Incidence;Individual;Infiltration;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;insight;Interdisciplinary Study;Invaded;kainate;Knock-out;Label;Learning;Life;man;Mediating;Medical emergency;Memory;Microglia;migration;Mission;Modeling;Molecular;monocyte;Mus;Myeloid Cells;nano-string;National Institute of Neurological Disorders and Stroke;Nerve Degeneration;Nervous System Disorder;neurobehavioral;neuroinflammation;Neurological emergencies;neuron loss;Neuronal Injury;Neurons;new therapeutic target;novel;object recognition;Outcome;Outcome Measure;Pathway interactions;Peripheral;pharmacologic;Phenotype;Pilocarpine;prevent;primary outcome;Process;Quality of life;Reaction;recruit;Residual state;Rodent;Role;Seizures;Serum Albumin;Status Epilepticus;success;Techniques;Testing;therapeutic target;Weight;Work

PROJECT_TITLE: Brain-invading monocytes promote the deleterious consequences of status epilepticus

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

PHR: Narrative The study proposes to detect novel circulating microbial metabolites associated with long-term weight loss in response to diet interventions. We will perform innovative analyses on the dynamic interrelationships of weight- loss diets, microbial metabolites, gut-organ/tissue cross talk, miRNAs, biochemical and clinical measures. Our study would lead to identification of novel modifiable targets for diet interventions, and improve precision obesity management.

PI_NAMEs: QI, LU  (contact)

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: Address;adipokines;Adipose tissue;Affect;Basal metabolic rate;Biochemical;Blood;Blood Pressure;Blood specimen;Body Weight Changes;Body Weight decreased;Cardiometabolic Disease;cardiometabolic risk;cardiometabolism;Ceramides;circulating microRNA;Circulation;Citric Acid Cycle;Clinical;Collection;Communication;Data;Development;Diet;Diet Modification;dietary;Dietary Factors;Dietary intake;Dietary Intervention;doubly-labeled water;Dual-Energy X-Ray Absorptiometry;Eicosanoids;energy balance;Fatty acid glycerol esters;Glucose;Goals;gut microbiota;Health;Heart;Hormones;host microbiota;Human;improved;Inflammation;innovation;insulin sensitivity;Intervention;Kidney;Knowledge;Lecithin;Lipids;Liver;Longitudinal Studies;Macronutrients Nutrition;Magnetic Resonance Imaging;Measures;Mediating;Metabolic;Metabolism;metabolomics;microbial;microbiota;MicroRNAs;Muscle;novel;Obesity;obesity development;obesity management;obesity prevention;obesity risk;Organ;Pancreas;Phosphatidylethanolamine;Plasma;Play;Prevention strategy;proctolin;prospective;remote interaction;Research;Resources;response;Role;Scanning;secondary analysis;sensor;Skeletal Muscle;Sphingomyelins;System;Systems Analysis;Tissues;total energy expenditure;Transducers;treatment strategy;Triglycerides;Volatile Fatty Acids;weight loss intervention;X-Ray Computed Tomography

PROJECT_TITLE: Weight-Loss Diet Intervention on Cardiometabolic Factors of Gut Microbiota

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Brain Disorders;Clinical Research;Genetics;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_DEPT: NEUROLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: In this study we will focus on the immunology of IL-7Rα, a genetic risk factor for MS, to enhance our understanding of the pathways and cellular interactions that promote CNS autoimmunity as well as investigate novel approaches to treat MS.

PI_NAMEs: ROSTAMI, A.M.  (contact)

PROGRAM_OFFICER_NAME: GUERAU, MIREIA

PROJECT_TERMS: Ablation;Affect;Agonist;analog;Animal Model;antagonist;B-Lymphocytes;base;Binding;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Physiology;Cells;central nervous system demyelinating disorder;Chronic;CNS autoimmunity;Complex;conditional knockout;cytokine;Cytoprotection;Data;Dendritic Cells;Development;Disease remission;Endothelin;Endothelin A Receptor;Endothelin-1;Etiology;Experimental Animal Model;Experimental Autoimmune Encephalomyelitis;experimental study;FOXP3 gene;Fumarates;Genes;Genetic;genetic approach;Genetic Polymorphism;genetic risk factor;genome wide association study;Granulocyte-Macrophage Colony-Stimulating Factor;Human;IL7 gene;Immune response;Immune Response Genes;Immunize;Immunology;In Vitro;in vivo;inducible gene expression;Inflammation;Inflammatory;Interleukin 2 Receptor Gamma;Interleukin 7 Receptor;Interleukin-9;Knockout Mice;Leukocytes;Literature;Mediating;Modeling;Molecular;Monoclonal Antibodies;Multiple Sclerosis;multiple sclerosis patient;multiple sclerosis treatment;Mus;Myelin;neuroinflammation;next generation sequencing;novel strategies;Pathogenesis;Pathogenicity;Pathway interactions;Play;polypeptide;Population;Predisposition;Production;Proteomics;receptor;receptor expression;Regulatory T-Lymphocyte;Relapse;Reporting;Resistance;Risk;Risk Factors;Role;Serum;Severities;Signal Pathway;Signal Transduction;single-cell RNA sequencing;T-Cell Development;T-Lymphocyte;Testing;Therapeutic;Therapeutic Effect;therapeutic evaluation;transcriptomics;treatment effect

PROJECT_TITLE: Role of IL-7R in CNS autoimmunity

STUDY_SECTION: HAI

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Cancer;Nanotechnology

ORG_CITY: TALLAHASSEE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: FLORIDA STATE UNIVERSITY

ORG_STATE: FL

PHR: Project Narrative The proposed development of biophysical approaches to functionally reconstitute membrane proteins in near native lipid membrane would enable high-resolution structural studies to better understand their function. Human cytP450s are the target for the treatment of various diseases including prostate and breast cancer. The outcome of the proposed structural studies will provide powerful insights into the molecular mechanism by which P450 redox partners influence the catalytic activity of cytP450 that is responsible for the metabolism of more than 70% of the current-day pharmaceuticals.

PI_NAMEs: RAMAMOORTHY, AYYALUSAMY  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: biophysical techniques;Catalysis;Chemicals;Complex;Cytochrome P450;Cytochromes;design;Detergents;Development;Diameter;Disease;divalent metal;Environment;Exhibits;G-Protein-Coupled Receptors;Guanidines;Heme;Homologous Gene;Human;insight;Integral Membrane Protein;Ions;Laboratories;Length;Malignant Breast Neoplasm;Malignant neoplasm of prostate;Malignant Neoplasms;Membrane;Membrane Lipids;Membrane Proteins;membrane reconstitution;Metabolism;Molecular;nanodisc technology;nanodisk;Outcome;Oxidation-Reduction;Oxidoreductase;Oxygenases;Pharmaceutical Preparations;Pharmacologic Substance;Polymers;prevent;protein complex;Protein Isoforms;Proteins;Resolution;solid state nuclear magnetic resonance;Structure;System;Techniques;Transmembrane Domain;Water

PROJECT_TITLE: Development of biophysical approaches to investigate high-resolution structure and dynamics of membrane proteins

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


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_CITY: BOSTON

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative:  More than a dozen states have proposed or plan to implement work requirements in Medicaid, yet evidence on the potential effects of these policies is limited. In 2020, Virginia will begin requiring beneficiaries to participate in at least 80 hours a month of employment or other “community engagement” activities to maintain coverage. With support from the state's Medicaid agency, we will conduct a randomized controlled trial studying the impacts of this policy on coverage, access to care, employment, and health, with a particular focus on changes in racial/ethnic and geographic disparities in these outcomes.

PI_NAMEs: LAYTON, TIMOTHY  (contact)

PROGRAM_OFFICER_NAME: DAGHER, RADA K

PROJECT_TERMS: Adult;Advocate;Affect;Affordable Care Act;Awareness;beneficiary;Caring;Communities;community engagement;Data;Deaths of despair;Disparity;disparity reduction;Drug Prescriptions;Education;Employment;Enrollment;ethnic disparity;ethnic minority;Ethnic Origin;experience;Experimental Designs;Family;Federal Government;federal policy;Financial Hardship;geographic disparity;Health;health care availability;health care disparity;health disparity;Health Insurance;Health Services Accessibility;Health Status;Healthcare;Hour;Household;improved;Income;Individual;Insurance;Insurance Coverage;interest;lens;Low income;Measures;Medicaid;Medical;Medical Assistance;Mental Health;Mental Health Services;Outcome;outcome prediction;Patient Self-Report;physical conditioning;Policies;Policy Maker;Population;Poverty;poverty reduction;Primary Care;programs;Public Assistance;Qualifying;Race;racial disparity;racial minority;Random Allocation;Randomized;Randomized, Controlled Trials;Reporting;Research Design;Resources;Risk;rural Americans;rural area;rural disparities;rural dwellers;Sampling;Services;socioeconomic disparity;suburb;Surveys;Testing;Uninsured;United States Centers for Medicare and Medicaid Services;Virginia;waiver;Work

PROJECT_TITLE: Work Requirements and Health Care Disparities in Medicaid: A RandomizedControlled Trial

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-HDM-A(57)]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding

ORG_CITY: MISSOULA

ORG_NAME: UNIVERSITY OF MONTANA

ORG_STATE: MT

PHR: Public Health Relevance This project will recruit 5 undergraduates each summer to spend 10 weeks conducting intensive research in active environmental health science laboratories at the Center for Environmental Health Sciences at the University of Montana. The Summer Undergraduate Research Program will also provide a number of supportive educational activities in order for the students to be prepared for successful careers in graduate education and careers in research.

PI_NAMEs: HOLIAN, ANDRIJ  (contact);MIGLIACCIO, CHRISTOPHER TODD

PROGRAM_OFFICER_NAME: HUMBLE, MICHAEL C

PROJECT_TERMS: Address;Basic Science;career;Career Choice;collaborative environment;Cultural Backgrounds;Data Analyses;disadvantaged student;Disparity population;Educational Activities;Environmental Health;Environmental Science;environmental toxicology;Event;experience;Faculty;faculty mentor;Future;Goals;Graduate Education;graduate school;graduate student;Grant;Health;Hearing;Human;Immersion;improved;Interdisciplinary Study;interest;Laboratories;Learning;Manuscripts;meetings;member;Mentors;Montana;NIH Program Announcements;Oral;Participant;Persons;Positioning Attribute;Postdoctoral Fellow;posters;Preparation;programs;public health relevance;Readiness;recruit;Recruitment Activity;Research;Research Activity;Research Personnel;Research Project Grants;responsible research conduct;Review Literature;Schools;Science;senior faculty;skills;social;Societies;Specialist;statistics;Structure;Students;summer research;Techniques;Toxicology;Training;undergraduate education;undergraduate research;undergraduate research experience;undergraduate student;Underrepresented Populations;United States National Institutes of Health;Universities;Work;Writing

PROJECT_TITLE: CEHS Summer Undergraduate Research Program: University of Montana


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Pain Research;Physical Activity;Physical Rehabilitation;Prevention;Rare Diseases;Rehabilitation

ORG_CITY: BIRMINGHAM

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PUBLIC HEALTH RELEVANCE: Fatigue and pain are two high incident symptoms threatening survivals among head and neck cancer patients after their treatment. For 6 weeks, the intervention group will receive a home-based Physical Activity intervention with fitness graded Motion Exergames (PAfitME), and the attention control group will receive NCI- based survivorship education and exergame equipment. We will test whether or not PAfitME is effective to improve fatigue, musculoskeletal pain, functional status, and QOL during the critical transition period from the treatment endpoint to self-management at home.

PI_NAMEs: WANG, HSIAO-LAN  (contact)

PROGRAM_OFFICER_NAME: SAMIMI, GOLI

PROJECT_TERMS: acceptability and feasibility;active method;Address;Adverse event;Aftercare;Age;Articular Range of Motion;attentional control;Behavior;Behavioral;Cancer Patient;cancer survival;Cancer Survivor;Cancer Survivorship;cancer therapy;chemoradiation;Chronic Disease;Clinical;Competence;Control Groups;Data;design;Education;effective intervention;Eligibility Determination;Enrollment;Enteral Feeding;Equipment;evidence base;Exercise;exercise intervention;exergame;experimental group;Fatigue;fitness;functional adaptation;functional status;Future;Goals;grasp;group intervention;Guidelines;Head and Neck Cancer;head and neck cancer patient;Health;health belief;Home;Home visitation;Impairment;improved;Individual;innovation;Intervention;Literature;Long-Term Effects;Malignant Neoplasms;Mediating;Mediation;Modeling;Motion;Musculoskeletal Pain;National Comprehensive Cancer Network;Operative Surgical Procedures;Outcome;Pain;Pain management;pain score;Participant;Patients;Performance;Phase;Phase II Clinical Trials;Physical activity;physical symptom;Pilot Projects;Pre-Post Tests;primary outcome;programs;public health relevance;Publishing;Quality of life;Radiation;Recommendation;Reporting;Research Design;response;Science;secondary outcome;Self Efficacy;Self Management;Series;sex;side effect;Skeletal Muscle;social cognitive theory;Stimulus;Sum;survivorship;symptom self management;Symptoms;Technology;telehealth;Testing;Time;Tissues;Tracheostomy procedure;treatment duration;Treatment-Related Cancer;Upper Extremity;visual feedback;Walking

PROJECT_TITLE: A Motion Exergaming Approach to Promote Self-Managing Fatigue and Pain after Head and Neck Cancer Treatment

STUDY_SECTION: BMIO

STUDY_SECTION_NAME: Behavioral Medicine, Interventions and Outcomes Study Section[BMIO]


NIH_SPENDING_CATS: Clinical Research;Infectious Diseases

PHR: Narrative The purpose of the application is to train undergraduate, masters and doctoral underrepresented minority students in biomedical and behavioral research in the U.S. or abroad annually. This will increase the number of proficiently trained researchers who understand health disparities populations and contribute to reducing and ultimately eliminating health disparities among racial and ethnic minority groups in the U.S. and abroad.

PI_NAMEs: JOLLY, PAULINE EVADNE (contact)

PROGRAM_OFFICER_NAME: BICKHAM-WRIGHT, UTIBE RONALD

PROJECT_TERMS: Achievement;Area;authority;Behavioral Research;Biomedical Research;Cardiometabolic Disease;Caring;Central America;Chronic Disease;Cities;Communicable Diseases;Computer software;Country;Data;Data Analyses;Data Collection;data management;Development;Diabetes Mellitus;doctoral student;Effectiveness;Experimental Designs;faculty mentor;Fertility;follow-up;Goals;Guatemala;Health;health care service;HIV;Human Papillomavirus;Hypertension;International;Jamaica;Malignant Neoplasms;Maternal and Child Health;Mentors;Methods;National Research Service Awards;Nepal;nutrition;Panama;Paper;Peru;Population;programs;Public Health;Publications;recruit;Reduce health disparities;Research;Research Ethics;Research Personnel;Research Project Grants;service delivery;Site;student mentoring;Students;symposium;Training;Training Programs;Travel;undergraduate student;Underrepresented Minority;underrepresented minority student;Visit;Work;Writing

PROJECT_TITLE: UAB Public Health/Biomedical Research Training Program


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Biotechnology;Genetics

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Project Narrative In this project we investigate the role the IL-23/IL-17 axis in the activation of innate immunity and the modulation of cell differentiation programs leading to bone and skin pathology as commonly occurs in autoimmunity.

PI_NAMEs: ADAMOPOULOS, IANNIS ELIAS (contact)

PROGRAM_OFFICER_NAME: MAO, SU-YAU

PROJECT_TERMS: Adoptive Transfer;Adult;aging population;American;Animal Model;Antibodies;Arthritis;Autoimmunity;Binding;Biological Markers;biomarker panel;bone;bone loss;Cell Differentiation process;Cell Surface Receptors;Cells;Cellular biology;cellular targeting;Clinical;Clinical Data;clinically significant;cohort;cytokine;Cytoplasmic Tail;Data;Development;digital imaging;Disabling condition;Disease;Disease Progression;Disputes;Dissection;economic impact;enthesitis;experimental study;Flow Cytometry;Functional disorder;Funding;Gene Expression Profiling;Gene Transfer;Genes;Helper-Inducer T-Lymphocyte;Hematopoietic stem cells;Histology;Human;IL17 gene;Image Analysis;Immunologics;In Vitro;in vitro Assay;in vivo;Individual;Inflammation;Inflammatory Arthritis;insight;interleukin-23;ITAM;ITGAM gene;Joints;Knock-in Mouse;Lectin;Lymphoid;Lymphoid Cell;Mediating;Modeling;Molecular;Molecular Target;Mus;mutant;Myelogenous;Myeloid Cell Activation;Myeloid Cells;Myelopoiesis;nanoprobe;Natural Immunity;neutrophil;novel;Organ;Osteoclasts;Pathogenesis;Pathogenicity;Pathologic;Pathology;Patients;Phenotype;Population;premature;prevent;programs;Proteins;Psoriasis;Psoriatic Arthritis;receptor;recruit;Regulation;Reporter;Research Personnel;Role;Sampling;Signal Transduction;Skin;skin organogenesis;Spondylarthropathies;T-Lymphocyte;Testing;Therapeutic Intervention;Time;transcriptome;transcriptome sequencing;Transducers;Transgenic Mice;Transmembrane Domain;transmission process;TYROBP gene

PROJECT_TITLE: The IL-23/IL-17 Axis in Inflammatory Arthritis

STUDY_SECTION: ACTS

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


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

ORG_CITY: FULLERTON

ORG_NAME: CALIFORNIA STATE UNIVERSITY FULLERTON

PHR: PROJECT NARRATIVE  Students belonging to groups underrepresented in biomedical, behavioral, clinical and social sciences research will receive training in these disciplines on subjects related to health disparities. These students will be part of the future cadre of researchers that thoroughly understand health disparities issues.

PI_NAMEs: TOLMASKY, MARCELO E (contact)

PROGRAM_OFFICER_NAME: OLADEINDE, YEWANDE A

PROJECT_TERMS: Address;Affect;AIDS prevention;Argentina;Awareness;Behavioral Sciences;California;care seeking;career;Caring;Clinical Sciences;Collaborations;Communication;Communities;Cultural Characteristics;Data Analyses;Data Collection;Degree Completion;design;Disadvantaged;Education;Educational workshop;Ensure;Environment;ethnic minority population;Ethnic Origin;experience;experimental study;Exposure to;Future;Goals;Health;health disparity;high risk;HIV;HIV/AIDS;Individual;International;Knowledge;Literature;Location;Medicine;meetings;member;Mentors;Minority Groups;Modeling;National Institute on Minority Health and Health Disparities;novel strategies;Oral;Persons;Population;posters;Prevention;programs;Publications;Publishing;Race;racial minority population;Reduce health disparities;Research;Research Institute;Research Personnel;Science;Scientist;social science research;Societies;Students;symposium;Thailand;Time;Training;training opportunity;Training Programs;Underrepresented Populations;United States;Universities

PROJECT_TITLE: LA Basin CSU MHRT Program


ADMINISTERING_IC: NR

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Maternal Health;Maternal Morbidity and Mortality;Networking and Information Technology R&D (NITRD);Nutrition;Obesity;Pediatric;Pregnancy;Prevention;Social Determinants of Health;Telehealth;Women's Health Research

ORG_CITY: BATON ROUGE

ORG_NAME: LSU PENNINGTON BIOMEDICAL RESEARCH CTR

PHR: Project Narrative More than one in eight women in the U.S. lived in poverty in 2015. Women with low incomes are the most vulnerable to maternal obesity, excess weight gain in pregnancy and poor birth outcomes. Lifestyle interventions during pregnancy positioned to reduce excess gestational weight gain may lower the risk of childhood obesity. The USDA Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) – a National program - is highly suited to deliver scalable and effective lifestyle interventions in low income and nutritionally at risk pregnant women. In this project we will develop an e-health intervention promoting healthy management of gestational weight gain that we refined for pregnant women receiving WIC benefits (Phase 1) and test the efficacy in a multi-site randomized controlled trial in Louisiana WIC (Phase 2).

PI_NAMEs: REDMAN, LEANNE MAREE (contact)

PROGRAM_OFFICER_NAME: LONG, SYLVIA ELISABETH

PROJECT_TERMS: Acculturation;Adherence;Attenuated;Behavior;behavior change;Behavioral;Belief;Birth;Body mass index;Body Weight decreased;Categories;Cellular Phone;Child;Chronic Disease;Client;Clinical Trials;Communities;community advisory board;Consultations;cost;cost effective;Cultural Sensitivity;design;Diet;dietary supplements;early childhood;Educational Curriculum;effectiveness testing;efficacy testing;eHealth;Enrollment;Ensure;excessive weight gain;Food;Fostering;Funding;Funding Opportunities;Future Generations;gestational weight gain;Goals;Guidelines;Health;health care service;health disparity populations;health literacy;Health Status;healthy weight;High Prevalence;improved;Incidence;Infant;innovation;Institute of Medicine (U.S.);intergenerational;Intervention;intervention effect;Interview;lifestyle intervention;Louisiana;Low income;maternal obesity;maternal risk;Minority Women;Moods;mother nutrition;Mothers;novel;nutrition;Nutritional;Nutritional status;Obesity;obesity in children;Outcome;Overweight;Participant;participant retention;patient oriented;Pattern;peer;Peer Group;Persons;Phase;Physical activity;Physiological;pilot trial;Population Heterogeneity;Positioning Attribute;postpartum weight;Poverty;Pregnancy;Pregnant Women;Prenatal Nutrition;prepregnancy obesity;prevent;programs;Quality of life;racial population;Randomized;Randomized, Controlled Trials;Recommendation;Reporting;Research;response;retention rate;Risk;Risk Factors;Risk Reduction;service providers;Site;smartphone application;Smoking;Special Supplemental Nutrition Program for Women, Infants, and Children;Structure;Surveys;System;Testing;Theory of Change;Time;Transportation;treatment as usual;Underserved Population;United States Department of Agriculture;United States National Institutes of Health;voucher;Weight;Weight Gain;Weight maintenance regimen;Woman;Women Status

PROJECT_TITLE: A pragmatic, scalable e-health intervention for management of gestational weight gain in low-income mothers

STUDY_SECTION: CLHP

STUDY_SECTION_NAME: Community-Level Health Promotion Study Section[CLHP]


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: WASHINGTON

ORG_DEPT: PATHOLOGY

ORG_NAME: GEORGE WASHINGTON UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative We will investigate control of antibodies information vaccine-induced antibody responses and innate immune responses associated with the If we are successful in defining the nature and the targets of these and the novel innate immune response pathways involved in viral control, incorporating this into vaccine design may facilitate the eventual development of an HIV v accine. SIVmac239 replication.

PI_NAMEs: WATKINS, DAVID I (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, DIANE M

PROJECT_TERMS: Animals;Antibodies;Antibody Response;antibody test;Binding;Biological Assay;CD8-Positive T-Lymphocytes;Cells;chemokine;Chronic Phase;cohort;cytokine;Cytomegalovirus;Development;Dose;Effector Cell;Genes;Grant;HIV;Immune response;Immune Response Genes;Immune signaling;Immunoglobulin G;Infection;Inflammasome;Innate Immune Response;Light;Macaca;Macaca mulatta;Mediating;Memory B-Lymphocyte;Monitor;Monoclonal Antibodies;Nature;novel;Outcome;Pathway interactions;Phagocytosis;Pharmacotherapy;polyclonal antibody;prevent;Rectum;Rhesus;RNA;Serum;SIV;T cell response;T-Cell Activation;Testing;Toll-Like Receptor Pathway;transcriptome;Vaccinated;Vaccine Design;vaccine trial;vaccine-induced antibodies;Vaccinee;Vaccines;Variant;Viral;Virus;Virus Replication

PROJECT_TITLE: The functional significance of CTL escape

STUDY_SECTION: VACC

STUDY_SECTION_NAME: HIV/AIDS Vaccines Study Section[VACC]


FUNDING_MECHANISM: OTHERS

ORG_CITY: PHOENIX

ORG_NAME: PHOENIX VA HEALTH CARE SYSTEM

ORG_STATE: AZ

PHR: Veterans are more likely to suffer from painful bone fractures than non-Veterans. Unfortunately, there are few strategies to manage this pain without significant side effects. Growing evidence indicates that bacteria that reside within the intestine contribute to inflammatory pain. The goal of this work is to determine the contribution of the intestinal microbiota to pain and metabolic response after fracture, and whether the gut microbiome can be targeted using probiotic dietary supplements to decrease pain throughout recovery from fractures. This therapeutic approach has the potential to decrease the reliance on harmful pain-relieving drugs and improve the quality of life in both Veterans and non-Veteran patients with bone fractures.

PI_NAMEs: ROBERTS, JOSEPH LEWIS (contact)

PROJECT_TERMS: Adherence;Adjuvant Analgesic;Affect;Antibiotics;antinociception;Award;Bacteria;Behavior assessment;Behavioral;Bifidobacterium;bone fracture repair;bone healing;Bone Injury;bone loss;bone mass;C57BL/6 Mouse;career;Cells;Chemoreceptors;Complement;Consumption;Data;desensitization;Development;dietary approach;Dietary Supplementation;dietary supplements;Environment;experience;experimental study;Female;Femoral Fractures;flexibility;Fracture;frailty;Functional impairment;functional outcomes;Goals;gut bacteria;gut microbiome;gut microbiota;healing;Human;Hypersensitivity;improved;improved outcome;Indigenous;Inflammation Mediators;Inflammatory;inflammatory modulation;inflammatory pain;Injury;innovation;Institution;intestinal epithelium;Intestines;Investigation;Knowledge;Lactobacillus casei;Long term disability;male;meetings;Mental Depression;Mentors;Metabolic;metabolic phenotype;Metabolism;metabolomics;Methods;microbiome;microbiota;microbiota metabolites;military veteran;Modality;Molecular;Molecular Weight;multidisciplinary;Mus;muscle form;Musculoskeletal;musculoskeletal injury;Musculoskeletal Pain;novel;novel therapeutic intervention;nutrition;Oral;Orthopedics;Pain;Pain management;Pain Measurement;pain outcome;pain relief;painful neuropathy;Patient-Focused Outcomes;Patients;Performance;Pharmaceutical Preparations;pharmacologic;Physical Function;prevent;probiotic supplementation;Probiotics;Production;programs;Quality of life;Recommendation;Recovery;Recurrence;Regimen;Rehabilitation therapy;Research;Research Personnel;response;Role;Serum;side effect;Signal Transduction;skills;Spinal Ganglia;systemic inflammatory response;Testing;Therapeutic;therapeutic target;Time;Tissues;Training;Veterans;Visceral pain;Weight-Bearing state;Work

PROJECT_TITLE: The contribution of the intestinal microbiota to fracture-induced pain

STUDY_SECTION_NAME: Career Development Program - Panel I[RRD8]


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

PHR: The objective of this proposal is to identify viral and host factors that promote reovirus killing of triple-negative breast cancer cells and define how DNA-damaging topoisomerase inhibitors impact reovirus biology. Based on preliminary data, we hypothesize that serotype 1 reovirus infection in the presence of topoisomerase inhibitors induces complementary cell death pathways that synergizes viral-mediated triple-negative breast cancer cell death. Knowledge gained from experiments in this proposal will enhance our understanding of how viruses promote cell death and illuminate the development of combinatorial therapeutics against triple-negative breast cancer.

PI_NAMEs: LOWEN, ANICE C (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Apoptosis;Biology;Breast Cancer Cell;cancer cell;cancer cell subtype;Cancer Etiology;cancer subtypes;cancer type;CASP3 gene;Caspase;Categories;Cell Death;Cell Death Induction;cell killing;cell transformation;Cells;Chemotherapy and/or radiation;Childhood;Clinical Trials;combinatorial;Cytotoxic Chemotherapy;cytotoxicity;Data;Development;Disease;DNA Damage;Double Stranded RNA Virus;Doxorubicin;Drug Delivery Systems;efficacy evaluation;Epirubicin;ERBB2 gene;Estrogen Receptors;Etoposide;experimental study;Growth Factor Receptors;high throughput screening;Human;Immune signaling;improved;Infection;Innate Immune Response;Integration Host Factors;Interleukin-24;Knowledge;Malignant Breast Neoplasm;Malignant Neoplasms;Mammalian Orthoreovirus;Mediating;neutralizing antibody;Oncolytic;Organoids;Outcome;Pathway interactions;Patients;personalized therapeutic;Phase;Plasmids;Progesterone Receptors;Property;Regimen;Reovirus;Reovirus 3;Reovirus Infections;Reovirus Type 1;response;reverse genetics;Role;Serotyping;Signal Pathway;small molecule inhibitor;Survival Rate;synergism;Testing;Therapeutic;Topoisomerase Inhibitors;Topotecan;transcriptome sequencing;triple-negative invasive breast carcinoma;tumor;Viral;Virus;Virus Diseases;virus host interaction;Women's mortality;women's treatment

PROJECT_TITLE: Development of Oncolytic Reovirus for Triple-Negative Breast Cancer

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


ORG_CITY: PITTSBURGH

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Cardiac rehabilitation (CR) is a secondary prevention program for patients with cardiovascular disease (CVD). It is especially valuable as CVD increasingly occurs in combination with comorbidity, frailty, and complexities of care that predispose patients to functional decline, disability, and high costs. Still, few Veterans participate in CR, in part because of the difficult logistics to attend. Promising Practice home-based CR (HBCR) was developed to increase CR participation, but many Veterans remain too limited by comorbidity and frailty for participation. A Transition to CR (T2CR) intervention is a face-to-face program that fosters vital skills, education, insights, motivation, and patient-provider relationships conducive to successful HBCR thereafter. This study compares Veterans eligible for CR who are randomized to T2CR intervention versus usual care. Differences in functional capacity, HBCR participation, and healthy days at home are compared over one year. Patients' experiences and providers' perspectives of barriers and facilitators to T2CR are also compared.

PI_NAMEs: FORMAN, DANIEL E. (contact)

PROJECT_TERMS: acceptability and feasibility;Activities of Daily Living;Acute;acute care;Address;Adherence;Aging;aging population;American Heart Association;barrier to care;Boston;Cardiac rehabilitation;Cardiology;Cardiovascular Diseases;Care given by nurses;Caring;Cessation of life;Clinical;comorbidity;Consolidated Framework for Implementation Research;Consultations;Control Locus;cost;COVID-19;COVID-19 risk;design;disability;Education;Effectiveness;effectiveness/implementation trial;Eligibility Determination;Ensure;Event;evidence base;Exercise;exercise training;experience;Feedback;Felis catus;follow-up;Fostering;frailty;functional decline;functional gain;Functional impairment;Future;Geriatrics;Goals;Growth;Health Care Costs;Health Personnel;Health Services Accessibility;Health Services Research;Healthcare;Healthcare Systems;Home;hospital readmission;Hospitalization;Hospitals;Hybrids;implementation framework;implementation science;implementation strategy;implementation trial;improved;innovation;insight;Intervention;Learning;Logistics;Long-Term Care;Measures;Medical;Medical center;Medication Management;Modeling;Moods;Motivation;multiple chronic conditions;novel;Nurse Practitioners;Older Population;Outcome;Patients;Perception;Performance;Phase;Phase Transition;Physical activity;Physical assessment;physical conditioning;Physical Function;Physical therapy;Prevention program;primary endpoint;Process;process improvement;programs;Progressive Disease;Provider;Psychological reinforcement;psychosocial;Quality of Care;Quality of life;Randomized;Randomized, Controlled Trials;Recovery;Recovery of Function;Recurrence;rehabilitation service;Reporting;research and development;Risk;Rural Health;Safety;satisfaction;Secondary Prevention;Self Efficacy;Site;skills;Social Psychology;Standardization;Structure;Survival Rate;Survivors;synergism;Telemedicine;Training Technics;treatment as usual;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Transition to Cardiac Rehabilitation (T2C) to Address Barriers of Multimorbidity and Frailty


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Emerging Infectious Diseases;Genetics;HIV/AIDS;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Bedaquiline is the first new TB drug to receive FDA approval in 40 years and has already transformed the treatment of multidrug- and extensively drug-resistant (M/XDR TB). Many patients, however, interrupt M/XDR TB therapy prematurely and because bedaquiline has an extremely long half-life, treatment interruptions pose a particular risk of causing bedaquiline resistance and eventual treatment failure. This study will investigate the risk of developing bedaquiline resistance after interruption of therapy in a cohort of patients with M/XDR TB in South Africa. Integrating traditional microbiology with novel genetic sequencing techniques, pharmacokinetic sampling, and pharmacometric modeling, the study addresses an urgent global public health problem that stands to undermine the utility of this new and critical medication.

PI_NAMEs: BRUST, JAMES C M (contact)

PROGRAM_OFFICER_NAME: LAUGHON, BARBARA E

PROJECT_TERMS: Address;Advisory Committees;Affect;Aftercare;Bacteria;Binding Proteins;Biological Assay;Caring;Cessation of life;Clinical;cohort;Companions;Complex;Death Rate;deep sequencing;Development;Disease;Drug Exposure;Drug Kinetics;drug repurposing;Drug resistance;Drug resistance in tuberculosis;Early treatment;Effectiveness;efflux pump;Enrollment;Epidemic;Exposure to;extensive drug resistance;Extreme drug resistant tuberculosis;Frequencies;Genes;Genetic;Genetic Polymorphism;genome sequencing;Genotype;Guidelines;Half-Life;high risk;HIV;HIV/TB;Hour;improved;Individual;individual patient;Intermediate resistance;Interruption;Leprosy;Linezolid;Measures;Meta-Analysis;Methods;Microbiology;Minority;Minority Groups;Modeling;mortality;mortality risk;Multidrug-Resistant Tuberculosis;Mutation;Mycobacterium tuberculosis;novel;novel therapeutics;Patients;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;pharmacokinetic model;Pharmacology;pharmacometrics;Phenotype;Plasma;Play;Population;Population Heterogeneity;Prediction of Response to Therapy;Predisposition;premature;Prevalence;Public Health;Pump;Recommendation;Regimen;Research Priority;Resistance;resistance mechanism;Resistance profile;Risk;Role;Sampling;scale up;side effect;single molecule;South Africa;Techniques;Testing;Time;treatment center;treatment duration;Treatment Failure;treatment program;Treatment Protocols;treatment risk;Tuberculosis;tuberculosis drugs;tuberculosis treatment;United States National Institutes of Health;whole genome

PROJECT_TITLE: Emergence of bedaquiline and clofazimine resistance after interruption of drug-resistant TB therapy in a high HIV prevalence setting

STUDY_SECTION: HCAC

STUDY_SECTION_NAME: HIV Coinfections and HIV Associated Cancers Study Section[HCAC]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Neurosciences

PHR: PROJECT NARRATIVE Dysfunctions of the prefrontal cortex (PFC) and posterior parietal cortex (PPC) have a deleterious impact on cognitive function, which is one of the most critical determinants of quality of life in patients. Furthermore, cognitive and behavioral deficits from PFC and PPC abnormalities are particularly challenging to treat. This proposal aims to cause widespread effects on cognitive function that could someday be harnessed for treatments by identifying and modulating the most influential areas of the PFC and PPC.

PI_NAMEs: NEE, DEREK EVAN (contact)

PROGRAM_OFFICER_NAME: ROSSI, ANDREW F

PROJECT_TERMS: Affect;Anatomy;Animal Model;Apical;Area;Attention deficit hyperactivity disorder;Behavior;Behavior Control;Behavioral;behavioral impairment;Biological Markers;Brain;brain behavior;Brain region;Cognition;Cognitive;cognitive control;Cognitive deficits;cognitive function;Communication;Computational Technique;Coupled;Data;Disease;Disease Progression;Functional disorder;Functional Magnetic Resonance Imaging;Future;Goals;Human;Huntington Disease;Impairment;improved;Impulsivity;inattention;Influentials;insight;interest;Lateral;Logic;Measurement;Mediating;Mental disorders;Methodology;Modeling;Monitor;Mood Disorders;Nervous System Disorder;neural;neuroimaging;novel;Parietal;Parietal Lobe;Parkinson Disease;Patients;Perception;Prefrontal Cortex;Process;Quality of life;Rehabilitation therapy;Resolution;Role;Schizophrenia;Stroke;Substance Addiction;Techniques;Testing;theories;Transcranial magnetic stimulation;Traumatic Brain Injury;Work

PROJECT_TITLE: Hierarchical Interactions Supporting Cognitive Control

STUDY_SECTION: CP

STUDY_SECTION_NAME: Cognition and Perception Study Section[CP]


ORG_CITY: HOUSTON

ORG_NAME: MICHAEL E DEBAKEY VA MEDICAL CENTER

ORG_STATE: TX

PHR: Advanced liver disease is a serious illness that disproportionately affects Veterans, many of whom hope for curative liver transplantation. However, too few receive a transplant and most continue to suffer from increasing symptoms and hospitalizations. We found gaps in advanced liver disease curative and supportive care. The proposed project employs a whole person, Veteran-centered approach that identifies Veterans with advanced liver disease using a population-based health management system, and integrates curative and early supportive care using a virtual outreach nurse care counselor based at a liver transplant center to (1) discuss patient’s understanding of illness severity and prognosis, (2) identify priorities and care preferences and (3) align curative and supportive care options to achieve patient priorities. Study outcomes include changes in (1) rates of consideration for liver transplantation, and (2) completion of serious illness discussions. Findings will inform adaptations to the intervention and facilitators for its dissemination across VHA.

PI_NAMEs: ASCH, STEVEN M.;KANWAL, FASIHA  (contact);NAIK, AANAND D.

PROJECT_TERMS: Adoption;Affect;care coordination;Care given by nurses;care preference;care seeking;Caring;Case Manager;Chronic Disease;Clinic;Clinical;Clinical effectiveness;Collaborations;Communication;Complex;Consent;cost;Decision Making;design;Disease;disease prognosis;Effectiveness;effectiveness evaluation;effectiveness trial;effectiveness/implementation design;effectiveness/implementation study;Electronic Health Record;Evaluation;evidence base;experience;falls;formative assessment;Gastroenterology;Goals;health management;health related quality of life;Hepatology;Hospitalization;Hybrids;implementation efforts;implementation evaluation;implementation facilitation;implementation framework;implementation outcomes;improved;informant;Infrastructure;innovation;Intervention;Interview;Knowledge;Leadership;Life Expectancy;Link;Liver;Liver diseases;liver transplantation;Los Angeles;Manuals;Measures;medical specialties;Mental Depression;Methods;military veteran;Modeling;mortality;multidisciplinary;Outcome;Outcome Study;outreach;Palliative Care;Participant;Patient Preferences;Patient-Focused Outcomes;Patients;Penetration;Perception;Persons;Pilot Projects;Policies;Population;population based;population health;preference;Procedures;Process;Proctor framework;Professional counselor;Prognosis;prognostic model;prognostication;programs;promoter;Promoting Action on Research Implementation in Health Services framework;Provider;Randomized;randomized, clinical trials;randomized, controlled study;Randomized, Controlled Trials;recruit;Reporting;routine care;satisfaction;screening;secondary outcome;Severity of illness;shared decision making;Site;staff intervention;Structure;Supportive care;Surveys;Symptom Burden;Symptoms;System;Testing;Time;tool;Training Programs;transplant centers;Transplantation;treatment as usual;United States Department of Veterans Affairs;uptake;Veterans;virtual;Visit;whole health;Work

PROJECT_TITLE: Integrating Veteran-Centered Care for Advanced Liver Disease (I-VCALD)

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


ORG_CITY: CLEVELAND

ORG_NAME: LOUIS STOKES CLEVELAND VA MEDICAL CENTER

ORG_STATE: OH

PHR: Incontinence associates with military service and post-traumatic stress disorder in both male and female Veterans. Neurogenic detrusor overactivity (NDO) is caused by spinal cord injury or disorder, or peripheral neurodegenerative conditions, and causes urine leakage at low volumes. NDO is disproportionately experienced by Veterans treatment effectiveness varies greatly between individuals. This project will demonstrate the feasibility of a new type of nerve stimulation—triggered sacral neuromodulation—to treat NDO in Veterans. A wireless bladder sensor will be inserted into the bladder to transmit a feedback signal enabling stimulation from a percutaneous lead. The wireless sensor will also measure NDO symptoms during simulated activities of daily living without catheters. Catheter-free detection of bladder activity will improve the outcomes of neuromodulation evaluations for Veterans with NDO. Future work could use the triggered neuromodulation system to study other methods of nerve stimulation to treat bladder, bowel, or sexual dysfunction.

PI_NAMEs: MAJERUS, STEVE  (contact)

PROJECT_TERMS: Activities of Daily Living;Affect;Algorithms;Autonomic Dysreflexia;Awareness;Behavior;Bladder;botulinum neurotoxin injection;Catheters;classification algorithm;Clinical;comorbidity;Computer software;Custom;Data;data exchange;decubitus ulcer;Detection;detection method;Diabetic Neuropathies;diaries;Disadvantaged;Disease;Effectiveness;Elderly;Evaluation;Event;experience;Extravasation;fall risk;Feasibility Studies;Feedback;Female;first-in-human;Frequencies;functional decline;Future;Goals;Home;Hour;Human;implantation;improved;improved outcome;Incontinence;Independent Living;Individual;Intestines;Kidney Failure;Label;Lead;Major Depressive Disorder;male;Measures;men;Meta-Analysis;Methods;military service;Modeling;Multiple Sclerosis;Nerve;Nerve Degeneration;neuroregulation;Outcome Measure;Parkinson Disease;Peripheral;Phase;Post-Traumatic Stress Disorders;pressure;Questionnaires;Radio;Rattus;Readiness;Reflux;Refractory;Reporting;Research;Research Project Grants;response;Risk;sensor;Sepsis;Sexual Dysfunction;Sheep;Signal Transduction;Social isolation;Spinal cord injury;Stroke;Symptoms;System;Technology;Testing;Time;tool;translational goal;Translational Research;Translations;transmission process;Treatment Effectiveness;treatment response;urinary;Urinary Incontinence;Urinary Retention;Urinary tract infection;Urine;Urodynamics;Veterans;wireless;wireless communication;wireless sensor;wireless transmission;Woman;Work

PROJECT_TITLE: Triggered sacral neuromodulation to treat neurogenic detrusor overactivity based on algorithmic classification of bladder filling status from wireless pressure data.

STUDY_SECTION_NAME: Rehabilitation Engineering & Prosthetics/Orthotics [RRD5]


ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE The clinical utility of whole genome sequencing to diagnose rare inherited conditions is significantly limited by our inability to interpret variants in the non-coding regions of the genome. This is particularly relevant since misregulation of a relatively new class of non-coding genes, dubbed long non-coding RNAs (lncRNAs), has been implicated in numerous inherited conditions, including neurodevelopmental disorders, but how these genes are normally regulated is understudied. This proposal takes a two-pronged approach to address these limitations through studying the spatiotemporal regulation of a lncRNA that is required for proper neuronal maturation, and by applying statistical genetics-based approaches to curate putative pathogenic non-coding variants in patients with neurodevelopmental disorders.

PI_NAMEs: WONTAKAL, SANDEEP NAGARAJ (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Address;Alleles;Binding;Binding Sites;Bioinformatics;Biological;Biological Sciences;blocking factor;Board Certification;Caenorhabditis elegans;career;career development;Cells;Cellular biology;chromatin immunoprecipitation;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Communities;Complement;Complex;Coupled;design;Development;Development Plans;Diagnosis;Disease;Doctor of Medicine;Doctor of Philosophy;Electrophoretic Mobility Shift Assay;Elements;Environment;experience;experimental study;Foundations;functional genomics;Genes;Genetic;genetic analysis;genetic approach;Genetic Screening;Genetic Transcription;Genome;genome sequencing;Genomic medicine;Genomics;Goals;Health;Human;In Vitro;in vivo;in vivo evaluation;Inherited;insight;interest;Leadership;Logic;male;Mediating;Mentors;Mentorship;Microscopy;Molecular;Mutate;Mutation;Nervous System;nervous system development;Neurobiology;neurodevelopment;Neurodevelopmental Disorder;neurogenetics;Neurons;Neurosciences;novel;Pathogenicity;Pathologist;Pathology;Pathway interactions;Patients;Pattern;Physicians;Process;professor;programs;Proteins;Rare Diseases;Recording of previous events;Regulation;Regulatory Element;Repression;Research;Research Personnel;RNA;Scientist;Sexual Maturation;skills;Solid;spatiotemporal;System;Testing;tool;Training;Transcription Coactivator;transcription factor;transcriptome sequencing;transmission process;Universities;Untranslated RNA;Up-Regulation;Variant;whole genome;Work

PROJECT_TITLE: Elucidating the Spatiotemporal Regulation of a Long Non-Coding RNA Required for Neurodevelopment

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Genetics;Kidney Disease;Pediatric;Polycystic Kidney Disease

PHR: Project Narrative/Relevance The disease-causing genes for autosomal-dominant polycystic kidney disease and many other genetic/cystic kidney diseases have been identified, but it remains largely unknown, how gene products perform their signaling functions in health and in disease pathogenesis. Many disease gene products localize to the antenna-like primary cilium of cells, where a specific complex of four proteins, the so-called inversin compartment, seems to act like a switch that can be turned into an “active” and an “inactive” signaling position. This study investigates the biochemical properties of this switch-like mechanism, the identity of upstream- and downstream actors in the signaling chain, and the cellular consequences when the signaling pathway is active, thereby exploring novel therapeutic approaches to genetic kidney disease.

PI_NAMEs: CZARNECKI, PETER G (contact)

PROGRAM_OFFICER_NAME: RANKIN, TRACY L

PROJECT_TERMS: Address;Adenylate Cyclase;Affect;Affinity;Alleles;Applications Grants;Autosomal Dominant Polycystic Kidney;Biochemical;Biology;cardiogenesis;Catalysis;Catalytic Domain;Cells;Central Nervous System;Cilia;ciliopathy;Communication;Complex;Congenital Heart Defects;Coupling;Cyclic AMP;Cystic Kidney Diseases;Data;Defect;design;Development;Disease;disease-causing mutation;Enzymes;Fluorescent Probes;G-Protein-Coupled Receptors;gene function;gene product;Generations;Genes;Genetic;GTP-Binding Protein alpha Subunits;GTP-Binding Protein alpha Subunits, Gs;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;Health;Heart;Heterotrimeric GTP-Binding Proteins;Hydrolysis;Individual;Kidney;Kidney Diseases;Kinetics;Knock-out;Left;Length;Link;Maps;Measures;Missense Mutation;Molecular;Mus;Mutation;nephrogenesis;novel;novel therapeutic intervention;novel therapeutics;Nucleotides;Organ;Organelles;Other Genetics;Outcome;Pathogenesis;Pathway interactions;Phenocopy;Polycystic Kidney Diseases;Positioning Attribute;Process;Property;protein complex;protein protein interaction;Proteins;receptor;Recombinants;recruit;response;Role;Second Messenger Systems;Signal Pathway;Signal Transduction;Structure;Syndrome;Tertiary Protein Structure;Testing;Vertebrates

PROJECT_TITLE: Novel signaling pathways in the ciliary inversin compartment

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Cancer;Childhood Leukemia;Gene Therapy;Genetics;Hematology;Immunotherapy;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Public Health Relevance Statement A recent new anti-cancer immunotherapy, chimeric antigen receptor (CAR) T cell therapy that specifically targets and kills tumor cells, has been highly successful in treating children and adults with leukemia who do not respond to any other treatment, saving many lives. However, these patients experience significant and sometimes life-threatening systemic (very high fever, very fast heart rate, very low blood pressure, etc.) and neurologic side effects (confusion, difficulty speaking, seizures, brain swelling, etc.), which can be fatal even under optimal drug management of these toxicities. Here, we aim to develop a new safer CAR T cells that is only active when the patient takes a plant-based medicine called Auxin, which would create a controllable CAR T cell therapy that is significantly safer in both the short and long term, thereby potentially preventing many ICU admissions and long hospital stays that are currently associated with CAR T cell therapies for leukemia.

PI_NAMEs: LORENZ, ULRIKE  (contact)

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: Acute Lymphocytic Leukemia;Admission activity;Adolescent;Adult;attenuation;Auxins;B lymphoid malignancy;B-cell precursor acute lymphoblastic leukemia cell;B-Lymphocytes;Beauty;Brain Edema;cancer diagnosis;cancer immunotherapy;CAR T cell therapy;CD19 gene;Cell Compartmentation;Central Nervous System Diseases;Characteristics;chemotherapy;Chemotherapy and/or radiation;Child;chimeric antigen receptor;chimeric antigen receptor T cells;Chronic;Clinic;Clinical;Clinical Trials;Confusion;cytokine release syndrome;Cytoplasm;cytotoxicity;Data;Development;Diagnosis;Dose;efficacy evaluation;experience;Face;Fever;Future;Goals;Heart Rate;Hematopoietic Stem Cell Transplantation;High Dose Chemotherapy;Hispanic;Human;Hypotension;immune effector cell-associated neurotoxicity syndrome;Immunoglobulins;In Vitro;in vivo;Incidence;Infusion procedures;Length of Stay;leukemia;leukemia treatment;Life;Long-Term Survivors;Malignant Neoplasms;Medical;Medication Management;Medicine;Modeling;Morbidity - disease rate;mortality risk;mouse model;Mus;neoplastic cell;Neurologic;neurotoxicity;novel;novel strategies;overexpression;Patients;pediatric patients;Pharmaceutical Preparations;Plant Growth Regulators;Plants;Population;pre-clinical;prevent;Prevention;Property;protein degradation;Protein Tyrosine Phosphatase;Proteins;PTPN6 gene;public health relevance;Recurrent disease;Refractory;Refractory Disease;Regulation;Relapse;Resolution;Risk;Safety;safety assessment;Seizures;side effect;Signal Transduction;Solid Neoplasm;Specificity;System;T-Cell Activation;T-Lymphocyte;Technology;Testing;Tissues;tool;Toxic effect;Translating;Work;Xenograft procedure;young adult

PROJECT_TITLE: A New Approach to Modulating CAR T Cell Activity