NIH_SPENDING_CATS: Aging;Cancer;Genetics;Rare Diseases

ORG_CITY: ATLANTA

ORG_NAME: GEORGIA STATE UNIVERSITY

PHR: PROJECT NARRATIVE The project will leverage new computational and hybrid modeling approaches to provide unified knowledge of the assembly, dynamics and function of key complexes in nucleotide excision repair – the most versatile pathway for removal of DNA damage resulting from exposure to environmental carcinogens. Unveiling the interplay of molecular-level mechanisms and disease mutations in these complexes will yield foundational understanding of severe genetic disorders associated with cancer, aging, and developmental defects – xeroderma pigmentosum, trichothiodystrophy, Cockayne syndrome and related diseases. Success of the project will thus impact understanding of the roles of environmental and genetic factors in human disease etiology, opening new avenues to devise effective treatments.

PI_NAMEs: IVANOV, IVAYLO NIKOLAEV (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Acceleration;adduct;Aging;Alkylating Agents;Area;assault;Binding Proteins;Biochemical;cancer predisposition;Carcinogen exposure;Cell Death;Cells;Cerebrooculofacioskeletal Syndrome;Chemicals;Cisplatin;Clinical;Cockayne Syndrome;Complex;Coupled;crosslink;Cryoelectron Microscopy;cytotoxic;Data;Defect;Detection;Deuterium;Development;Disease;disease phenotype;diverse data;DNA;DNA biosynthesis;DNA Damage;DNA lesion;DNA Repair;DNA Repair Pathway;ds-DNA;effective therapy;Elements;Endogenous Factors;Environmental Carcinogens;Environmental Health;Environmental Risk Factor;Epitopes;ERCC3 gene;Etiology;Evolution;Excision;experience;experimental group;experimental study;Exposure to;Foundations;Free Energy;gene repair;Genetic;Genetic Diseases;Genetic Transcription;Genome;Genomic DNA;Goals;Health;helicase;Heterogeneity;Human;human disease;Hybrids;Hydrogen;Impairment;Individual;insight;Investigation;Knowledge;Lesion;Letters;Maintenance;Malignant Neoplasms;Mass Spectrum Analysis;Methods;mobile computing;Modeling;Modification;Molecular;Molecular Conformation;Motion;Mutation;Nature;Nerve Degeneration;Normal Range;novel;nuclease;Nucleotide Excision Repair;Outcome;parallel computer;pathological aging;Pathway Analysis;Pathway interactions;Patients;Phenotype;Platinum adduct;Positioning Attribute;Predisposition;Premature aging syndrome;Process;Proliferating;protein complex;Proteins;Pyrimidine Dimers;Reactive Oxygen Species;Regulation;Repair Complex;repaired;Resolution;Resources;Roentgen Rays;Role;Sampling;Scanning;Science;Single-Stranded DNA;Site;Site-Directed Mutagenesis;structural biology;Structure;success;Supercomputing;Surgical incisions;Syndrome;Techniques;Toxin;transcription factor TFIIH;Trichothiodystrophy;Ultraviolet Rays;Work;Xeroderma Pigmentosum;XPA gene

PROJECT_TITLE: Integrative Modeling of Biomolecular Machinery in Nucleotide Excision Repair

STUDY_SECTION: MSFD

STUDY_SECTION_NAME: Macromolecular Structure and Function D Study Section[MSFD]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Rare Diseases

ORG_CITY: BIRMINGHAM

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: We propose to characterize the role of MafB in the regulation of the NLRP3 inflammasome activation and bacterial pneumonia caused acute lung injury (ALI). We aim to provide solid foundation for targeting MafB in treating ALI.

PI_NAMEs: LIU, GANG  (contact)

PROGRAM_OFFICER_NAME: SINGLETON, KENTNER L

PROJECT_TERMS: Acute Lung Injury;antimicrobial;Apoptosis;Bacterial Pneumonia;CASP1 gene;Cell Death;complement system;cytokine;Data;Disease;Down-Regulation;Foundations;Genetic Transcription;IL18 gene;Immune system;Immune System Diseases;In Vitro;in vivo;Infection;Inflammasome;Inflammatory;Inflammatory Response;insight;Interleukin-1 beta;Investigation;knock-down;Knock-out;Lens development;Light;Lung;lung injury;Lymphangiogenesis;Lytic;Macrophage;Mediating;member;microbial;multicatalytic endopeptidase complex;Mus;Natural Immunity;novel;overexpression;Pathogenesis;Phagocytosis;pharmacologic;Play;Process;Production;Proteins;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Pulmonary Inflammation;Regulation;response;Review Literature;Role;sensor;Solid;System;Testing;therapeutic target;therapeutically effective;tissue injury;transcription factor;Ubiquitin

PROJECT_TITLE: Mechanism and targeting of inflammasome activation in lung inflammation and injury

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: PHILADELPHIA

ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

ORG_STATE: PA

PHR: Cardiometabolic disorders including obesity, insulin resistance, dyslipidemia, and type 2 diabetes are highly prevalent among U.S. Veterans and serve as major factors in the development of heart, vascular and liver diseases. We have assembled a multi-disciplinary research team comprised of investigators with expertise in cardiovascular and metabolic disease, clinical and epidemiological research, EHR based research methods, genetic epidemiology, and statistical genetics. We now propose to build upon the momentum of our currently funded project (“Genetics of Cardiometabolic Diseases in the VA Population”) and further elucidate the genetic basis of the longitudinal progression of cardiometabolic traits, thereby informing more targeted genomic medicine-based disease management throughout the course of Veterans' lives.

PI_NAMEs: CHANG, KYONG-MI  (contact);TSAO, PHILIP S

PROJECT_TERMS: Abdominal Aortic Aneurysm;Academic Medical Centers;Address;Amputation;Award;biobank;Biological Markers;Body mass index;Cardiometabolic Disease;cardiometabolism;Cardiovascular Diseases;Clinical;Clinical effectiveness;Clinical Research;clinical risk;clinically relevant;cohort;Communities;cooperative study;Coronary Arteriosclerosis;Cross-Sectional Studies;Data;Development;Disease;Disease Management;Disease Progression;Dyslipidemias;EHR research;Electronic Health Record;Enrollment;Environment;Environmental Risk Factor;epidemiology study;experience;Family;Funding;Genetic;Genetic Determinism;genetic epidemiology;Genetic Risk;genome wide association study;Genomic medicine;Genomics;Goals;Growth;Health;Healthcare Systems;Heart Diseases;Heart failure;Height;improved;Information Systems;insight;Insulin Resistance;Interdisciplinary Study;Investigation;Life Style;lifestyle factors;Link;Lipids;Liver Cirrhosis;Liver diseases;macrovascular disease;Malignant neoplasm of liver;Manuscripts;Measures;Medical center;meetings;Mendelian randomization;Metabolic Diseases;Methodology;Methods;Minority Groups;Modeling;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Participant;Peripheral arterial disease;Phenotype;phenotypic data;phenotyping algorithm;pleiotropism;polygenic risk score;Population;pre-clinical;Prediabetes syndrome;programs;prospective;Publishing;Rare Diseases;Research Methodology;Research Personnel;Risk Factors;Risk Management;risk prediction;risk prediction model;risk variant;Safety;Science;Susceptibility Gene;Testing;Therapeutic Intervention;therapeutic target;Time;trait;Vascular Diseases;Veterans;web platform;working group


NIH_SPENDING_CATS: Adolescent Sexual Activity;Behavioral and Social Science;Data Science;HIV/AIDS;Infectious Diseases;Pediatric;Pediatric - AIDS;Prevention

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE HIV/AIDS is a leading cause of morbidity and mortality among children and adolescents, and robust estimates of the HIV burden among these age groups are needed to inform intervention priorities and monitor progress toward global targets. The goal of this study is to address limitations of existing methods by triangulating empirical data sources to produce more accurate and comprehensive estimates of pediatric HIV burden than current statistics, including the first-ever global estimates of new HIV infections among young adolescents, as well as insight into the unique contributions of biomedical, behavioral, and structural factors on the burden of HIV/AIDS in children and young adolescents. We will do so by assembling and triangulating data sources; quantifying the relationship between risk and protective factors and child/adolescent HIV burden; and forecasting the future burden of HIV among children/adolescents through 2040 based on current trends in incidence, prevalence, and mortality, and exposure to risk and protective factors.

PI_NAMEs: KYU, HMWE HMWE (contact)

PROGRAM_OFFICER_NAME: MCKAIG, ROSEMARY G

PROJECT_TERMS: Address;Adolescent;Adult;Adult women;African;Age;age group;antiretroviral therapy;Automobile Driving;Behavioral;Big Data;Birth;burden of illness;Caring;Cessation of life;Child;Childhood;condoms;Consensus;Country;Data;Data Sources;diverse data;Education;Epidemic;Exposure to;Fibrinogen;Future;Goals;Health;health care quality;HIV;HIV Infections;HIV-infected adolescents;HIV/AIDS;Human immunodeficiency virus test;Incidence;Infection;insight;interactive visualization;Intervention;Link;Location;Measures;Methods;Modeling;Monitor;Morbidity - disease rate;mortality;Mother-to-child HIV transmission;pediatric human immunodeficiency virus;Policies;Population;Prevalence;Prevention;Probability;protective factors;rate of change;Risk;Risk Behaviors;Risk Factors;Role;Series;sex;Sex Behavior;sexual debut;Sexual Partners;Source;statistics;structural determinants;Substance abuse problem;Time;tool;transmission process;trend;Vertical Disease Transmission;Visualization software;Work

PROJECT_TITLE: Quantification of HIV burden and the biomedical, structural, and behavioral factors influencing HIV/AIDS among children and young adolescents

STUDY_SECTION: PPAH

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


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Kidney Disease;Networking and Information Technology R&D (NITRD);Patient Safety

ORG_CITY: MANHASSET

ORG_NAME: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH

ORG_STATE: NY

PHR: PROJECT NARRATIVE The care for patients with acute kidney injury (AKI) is suboptimal when they transition from hospital to outpatient care, yet challenging to overcome because of poor AKI communication both to outpatient providers and patients. To improve AKI information flow to providers and patients, the proposed study aims to develop and evaluate AKI discharge summary tool in the electronic health records, and text messaging tool that supports patient education and self-management behavior. Improving AKI communication through these tools will improve the clinical care of patients with AKI and reduce morbidity.

PI_NAMEs: NG, JIA HWEI  (contact)

PROGRAM_OFFICER_NAME: GREER, RAQUEL CHARLES

PROJECT_TERMS: acute care;Acute Renal Failure with Renal Papillary Necrosis;Address;Agreement;Ambulatory Care;Automated Abstracting;Award;Behavior;Behavior Therapy;Behavioral Sciences;Biometry;career;career development;Caring;Cessation of life;clinical care;clinical epidemiology;Communication;cost;Critical Illness;Data;Data Analyses;design;Development;Diagnosis;Diet;dietary restriction;digital;digital health;digital solutions;Documentation;Education;Effectiveness;effectiveness evaluation;effectiveness testing;efficacy outcomes;electronic health information;Electronic Health Record;Enrollment;Environment;Epidemiology;epidemiology study;Evaluation;experience;Fostering;Foundations;Future;Goals;Health;health application;health information technology;Health Personnel;hospital care;hospital readmission;Hospitalization;Hospitals;improved;Instruction;Intervention;intervention refinement;Intervention Trial;Interview;K-Series Research Career Programs;Kidney;Kidney Failure;Knowledge;Knowledge Management;Libraries;Link;Managed Care;Master of Science;Measures;Medical;medical schools;Mentors;Mentorship;Monitor;Morbidity - disease rate;Motivation;multidisciplinary;Obesity;Outcome;Outcome Measure;Outpatients;Pamphlets;Patient Care;Patient Education;patient oriented;Patients;Pennsylvania;Pharmaceutical Preparations;Phase;Pilot Projects;pilot trial;Positioning Attribute;Primary Care Physician;Printing;programs;prototype;Provider;Public Health Informatics;Qualitative Research;Questionnaires;Randomized;Randomized, Controlled Trials;Reading;Recovery;Recurrence;Renal function;Research;Research Design;Research Personnel;Risk;Self Determination;Self Management;Signal Transduction;skills;Structure;support tools;Surveys;Telephone;Testing;Text Messaging;theories;therapy design;therapy development;Time;tool;Training;Treatment Efficacy;trial design;Universities;usability;Work

PROJECT_TITLE: Using Digital Solutions to Improve Transition of Care for Patients with Acute Kidney Injury

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Immunization;Immunotherapy;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Specific antibodies that block many strains of HIV are called broadly neutralizing antibodies or bnAbs. Rare people living with HIV (PLWH) develop these antibodies in their blood and others may have early or partially active antibodies. The purpose of this project is to conduct a clinical study of a new vaccine, called Trimer 4571, to determine if the vaccine is safe in PLWH and if it improves the antibody response to HIV. Additionally, the study will see if the vaccine has any impact on the HIV reservoir in blood cells. If successful, this may pave the way toward achieving sustained remission of HIV in the absence of antiretroviral therapy.

PI_NAMEs: RIDDLER, SHARON  (contact)

PROGRAM_OFFICER_NAME: MAHON III, ROBERT N

PROJECT_TERMS: Adjuvant;Adverse event;Affinity;Aluminum Hydroxide;aluminum sulfate;Animal Model;Anti-viral Therapy;Antibodies;Antibody Response;Antigen Presentation;Antigens;antiretroviral therapy;Apical;Autologous;Automobile Driving;B cell repertoire;B-Lymphocytes;Binding;Biological Assay;Blinded;Blocking Antibodies;Blood;Blood Cells;CD8-Positive T-Lymphocytes;Cell Lineage;Cells;Chronic;Clinical Research;Clinical Trials;cohort;Data;design;Development;Disease remission;disulfide bond;DNA;Dose;Double-Blind Method;Engineering;Epitopes;Exhibits;follow-up;Frequencies;Genetic Transcription;genome sequencing;Glycoproteins;Goals;HIV;HIV Antibodies;HIV envelope protein;HIV immunization;HIV vaccine;HIV-1;Human;Immune response;Immunization;immunogenic;immunogenicity;Immunoglobulin Somatic Hypermutation;Immunologics;Immunotherapeutic agent;improved;in vivo;Individual;Infection;innovation;insight;Intervention;Knock-out;Macaca;Measures;Molecular Conformation;Monoclonal Antibodies;Mutation;National Institute of Allergy and Infectious Disease;neutralizing antibody;next generation sequencing;NIH Vaccine Research Center;non-Native;novel;novel vaccines;Participant;passive antibodies;Pathway interactions;peripheral blood;Persons;Phase;Phylogenetic Analysis;Placebo Control;Placebos;Plasma;Population;Prevention;Preventive vaccine;Randomized;Reporting;Research;Residual state;response;RNA;Safety;Sampling;Scientist;secondary endpoint;Serum;Specificity;Structure;Surface;T cell response;Testing;therapy development;Thinking;Time;Vaccination;vaccine candidate;vaccine development;Vaccine Research;Vaccine Therapy;Vaccines;Viral;Viral Physiology;Viremia;Virion;Virus

PROJECT_TITLE: Native-like Envelope Trimer Therapeutic Vaccination for Induction of Broadly Neutralizing Antibodies to Facilitate HIV Functional Cure


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_DEPT: PHYSICAL MEDICINE & REHAB

PHR: PROJECT NARRATIVE  The impaired sensory function that results from lower-limb amputation often causes reduced balance control and an increased risk of falling. Electrical stimulation of the lateral spinal cord in the low back can produce sensations that feel like they come from the missing limb, although currently available electrodes often produce sensations that cover large regions of the missing foot and residual limb. In this project, we will perform large animal experiments and computational modelling studies to develop new electrodes for lateral spinal cord stimulation and we will chronically implant these devices near the spinal cord in pigs to measure their stability and safety over time.

PI_NAMEs: FISHER, LEE E (contact);LEMPKA, SCOTT F

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: Action Potentials;Amputees;Anatomy;Animal Experiments;Animals;Ankle;Area;Back;Chronic;Complex;Computer Models;Computer Simulation;Custom;Data;design;Development;Devices;Diameter;Distal;Dorsal;Dura Mater;Electric Stimulation;Electrodes;Elements;epidural space;Equilibrium;Esthesia;Experimental Animal Model;experimental study;fall risk;Family suidae;Felis catus;flexibility;foot;Gait;Geometry;Goals;Hand;high resolution imaging;Hindlimb;Histologic;Hour;Human;Image;Impairment;Implant;implantable device;implantation;improved;Individual;Injury;Intractable Pain;Lateral;limb amputation;Limb Prosthesis;Limb structure;Lower Extremity;Measurement;Measures;mechanical properties;Mechanics;meter;Microsurgery;Modeling;Nerve;nerve supply;neural;neurophysiology;Neurostimulation procedures of spinal cord tissue;novel;Operative Surgical Procedures;Pattern;Peripheral Nerve Stimulation;Peripheral Nerves;Persons;pressure;prosthesis control;Resected;residual limb;response;Safety;Sensory;sensory feedback;Silicones;somatosensory;Spinal Cord;spinal nerve posterior root;Structure;Study models;Surface;System;Techniques;Thick;Thinness;Time;tissue injury;Tissues;tool;Travel;Width

PROJECT_TITLE: Electrodes for selective stimulation of the lateral spinal cord to restore sensation after lower-limb amputation

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_NAME: RESEARCH INST OF FOX CHASE CAN CTR

PHR: PROJECT NARRATIVE There are approximately 55,000 deaths from breast and ovarian cancer annually in the United States, with BRCA1 and BRCA2 mutations found in 5-7% of breast and 6-15% of ovarian cancers cases. PARP inhibitor therapies extend the lives of BRCA1/2 mutation carrying patients; however, drug resistance invariably emerges. DNA polymerase theta inhibitors (Polθi) represent another promising approach, the goal of this project is to identify biological factors that determine Polθi sensitivity.

PI_NAMEs: JOHNSON, NEIL  (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Alleles;Biological Assay;Biological Factors;Biological Markers;BRCA mutations;BRCA1 gene;BRCA1 Mutation;BRCA2 Mutation;Breast;Cancer cell line;Cancer Patient;cancer therapy;Cell Line;cell type;Cells;Cessation of life;Chromosome Pairing;Clinical;clinical application;Clinical Research;Collaborations;Data;Dependence;DNA;DNA biosynthesis;DNA Repair;DNA Repair Pathway;DNA sequencing;DNA-Directed DNA Polymerase;Drug resistance;Event;Excision;Future;Genetic;Goals;homologous recombination;homologous recombination deficiency;Human;Immunofluorescence Microscopy;In Vitro;in vivo;inhibitor;inhibitor therapy;insight;Knock-out;Knockout Mice;Knowledge;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Measures;Mediating;Molecular;mutant;Mutate;Names;nuclease;Outcome;patient derived xenograft model;patient population;patient stratification;Patients;pharmacologic;Poly(ADP-ribose) Polymerase Inhibitor;Poly(ADP-ribose) Polymerases;Polymerase;preclinical development;Process;Proteins;Publishing;refractory cancer;repaired;Reporter;Resistance;Role;Single-Stranded DNA;Site;small molecule;small molecule inhibitor;Testing;therapeutic target;therapeutically effective;therapy development;treatment strategy;United States;Work

PROJECT_TITLE: Assessing DNA polymerase theta as a therapeutic target in BRCA1 mutant cancer

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


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project narrative We have found that IgM exacerbated obesity, enhanced inflammation and altered gut microbiota in an AID mouse model and we identified that IgM-bound gut bacteria were elevated in adolescent patients with obesity and type 2 diabetes (T2D). We hypothesize IgM antibodies and IgM-bound gut bacteria cause obesity and metabolic dysfunction and we will test the hypothesis in mouse and man, in vitro and in vivo, in three specific aims.

PI_NAMEs: WEN, LI  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Acceleration;activation-induced cytidine deaminase;Address;Adipose tissue;Adolescent;Adolescent obesity;adolescent patient;Adult;aged;Anti-Inflammatory Agents;Antibodies;B-Lymphocytes;Binding;Bone Marrow;Cell Compartmentation;Cell Physiology;Cells;Childhood;Circulation;Crowns;cytokine;Data;design;Endotoxins;Essential Fatty Acids;Etiology;Fatty acid glycerol esters;Germ-Free;gut bacteria;gut dysbiosis;gut microbiota;Health;Human;humoral immunity deficiency;Immune;Immune response;Immunoglobulin G;Immunoglobulin M;Immunoglobulins;Immunologic Memory;impaired glucose tolerance;Impairment;In Vitro;in vivo;Inflammation;Inflammatory;influenza infection;Insulin Resistance;Intestinal permeability;Knowledge;Life;Lymphoid Cell;man;Mediating;Metabolic;Metabolic dysfunction;Metabolism;Molecular;mouse model;Mucous Membrane;Mus;Non-Insulin-Dependent Diabetes Mellitus;Obese Mice;obese patients;obese person;Obesity;obesity development;Pathogenicity;Patients;Persons;Play;Prevalence;Prevention therapy;Production;Role;Silver;small molecule;Structure;Study models;subcutaneous;T cell regulation;T-Lymphocyte;Testing;Tissues;type 2 diabetes in children;Weight Gain

PROJECT_TITLE: Antibody and gut bacteria in obesity and T2D

STUDY_SECTION: CIDO

STUDY_SECTION_NAME: Clinical and Integrative Diabetes and Obesity Study Section[CIDO]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases;Pediatric;Pediatric - AIDS;Prevention

ORG_CITY: NEW ORLEANS

ORG_DEPT: PATHOLOGY

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Principal Investigators (Last, first, middle): Xu, Huanbin PROJECT NARRATIVE: Despite remarkable advances in prevention of vertical HIV-1 transmission, pediatric HIV infections still occur peripartum rather than through breastfeeding, however, there is little data to guide the optimal early treatment regimens in vulnerable neonates with high risk of MTCT. Our primary findings indicate that infant macaques intravenously infected with pathogenic SIV at birth achieve sustained virologic remission by 9-months of early intervention, suggesting pediatric HIV remission is achievable in a proportion of infants infected with or exposed to HIV. Assessing the impact of early viral reservoir on the treatment outcomes, determining optimal prevention intervention strategies for a sustained state of ART-free viral remission, and exploring the antiretroviral pharmacokinetics and immune alteration in unique infants using early prevention interventions, will accelerate translational treatment towards pediatric HIV remission.

PI_NAMEs: XU, HUANBIN  (contact)

PROGRAM_OFFICER_NAME: RAO, VASUDEV RAMACHANDRA

PROJECT_TERMS: Acceleration;Address;Adult;Affect;Aftercare;Age;analog;Anatomy;Animals;Anti-Retroviral Agents;Anti-viral Agents;Birth;Breast Feeding;Cells;Child;Childhood;Clinical Data;Clinical Trials;comparative;Data;Development;Disease remission;Drug Kinetics;Early Intervention;Early treatment;efficacy evaluation;Equilibrium;Evaluation;Exposure to;Formulation;Genetic;Half-Life;high risk;HIV;HIV Infections;HIV therapy;HIV-1;Immune;Immune system;Immunologics;infancy;Infant;infant infection;Infection;inhibitor;Injectable;insight;Integrase;Interruption;Intervention;Intravenous;Knowledge;Lymphoid Tissue;Macaca;Metabolism;Modeling;Molecular;Monitor;Neonatal;neonate;Newborn Infant;Outcome;Pathogenicity;pediatric human immunodeficiency virus;pediatric human immunodeficiency virus infection;Penetration;Perinatal;Pharmaceutical Preparations;preclinical trial;prevent;Prevention;preventive intervention;Preventive treatment;Primates;Principal Investigator;prophylactic;Publishing;Recommendation;Regenerative capacity;Regimen;Residual state;Safety;Sampling;simian human immunodeficiency virus;Site;SIV;Tissue Sample;transmission process;treatment duration;Treatment outcome;Treatment Protocols;treatment strategy;truvada;Viral;Viral Genome;Viral Load result;Viral Physiology;viral rebound;Viral reservoir;Viremia;Virus Integration;Withholding Treatment

PROJECT_TITLE: Early prevention interventions towards ART-free pediatric HIV remission

STUDY_SECTION: HCCS

STUDY_SECTION_NAME: HIV Comorbidities and Clinical Studies Study Section[HCCS]


NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Orphan Drug;Patient Safety;Prevention;Rare Diseases

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: PROJECT NARRATIVE The aim of inter-Institutional cooperative clinical research is to advance our understanding of cancer prevention, pre- cancers, and both benign and malignant processes and, thereby, to improve our ability to treat people at risk or afflicted with them. These aims are accomplished by resolving scientific questions of importance regarding cancer biology and therapy through the cooperation of selected Institutions that can pool their intellectual, technical, and patient resources. The rapid accumulation of clinical data and experience through cooperative group research expedites progress in cancer therapy.

PI_NAMEs: LELE, SHASHIKANT ;LEVINE, ELLIS G (contact);PUZANOV, IGOR ;SINGH, ANURAG KISHOR

PROGRAM_OFFICER_NAME: MOONEY, MARGARET M

PROJECT_TERMS: Benign;Biological;Biometry;Cancer Biology;Cancer Patient;cancer prevention;cancer therapy;Clinical Data;Clinical Protocols;Clinical Research;Clinical Treatment;Clinical Trials;Data;data submission;Enrollment;experience;Grant;Imaging Techniques;improved;Institution;inter-institutional;Knowledge;Lead;Malignant - descriptor;Manuscripts;member;Molecular;novel therapeutics;Operative Surgical Procedures;Patient advocacy;Patients;Phase;Populations at Risk;premalignant;Preparation;Process;Productivity;prognostic;Protocols documentation;Quality of life;Radiation;Radiology Specialty;rare cancer;Research;Research Personnel;Resources;response;Roswell Park Cancer Institute;Site;Specimen;Techniques;Therapeutic;therapy resistant;timeline;treatment trial

PROJECT_TITLE: Network Lead Academic Participating Site Grant from the Roswell Park Cancer Institute


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: BURLINGTON

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE

ORG_STATE: VT

PHR: PROJECT NARRATIVE Aging is primarily studied with samples that begin in midlife or later and assess individuals yearly or less often. Furthermore, a premature mortality crisis has ravaged rural communities where economic opportunities and key infrastructures have declined and social disintegration has increased The objective of our set of complementary aims is to develop a new data resource that captures the full arc of a life with intimate detail about living and aging in a rural context.

PI_NAMEs: CAGNEY, KATHLEEN A;COPELAND, WILLIAM  (contact);DODGE, KENNETH A;HOTZ, VINCENT JOSEPH

PROGRAM_OFFICER_NAME: KARRAKER, AMELIA WILKES

PROJECT_TERMS: actigraphy;Adult;Affect;Age;age related chronic disease;Aging;aging process;Alcoholic Liver Diseases;American Indians;Appalachian Region;Attitude;Biological Assay;biopsychosocial;Blood;Blood Banks;Blood Pressure;Censuses;Childhood;Code;Cognition;Cognitive;Collaborations;Collection;Communities;computerized;Coupled;Data;Data Collection;data harmonization;Data Linkages;data resource;Data Set;Databases;design;Development;Dryness;early experience;Ecological momentary assessment;Economics;Education;Educational workshop;Equilibrium;Ethnic Origin;experience;FAIR principles;Health;Health and Retirement Study;Healthcare;Height;high risk;Home;Income;Individual;Informal Social Control;Infrastructure;innovation;Interview;laptop;large scale data;Life;Longitudinal Studies;Measures;member;Mental Health;Methodology;Methods;middle age;Modeling;Monitor;Movement;multidisciplinary;National Archive;National Longitudinal Survey of Adolescent to Adult Health;Neighborhoods;Neurocognitive;normal aging;novel;Opioid;Participant;Pattern;Pharmaceutical Preparations;Physical activity;Physical assessment;physical conditioning;Poisoning;population health;Premature Mortality;Process;programs;prospective;Protocols documentation;Public Health;pulmonary function;Quasi-experiment;Race;Recontacts;Research;Research Personnel;residence;Resources;Risk;Risk Factors;Rural;Rural Appalachia;Rural Community;Sampling;Scientist;Sleep;social;social cohesion;Social Functioning;social observations;socioeconomics;Spottings;Structure;Study models;Suicide;Surveys;symposium;Walking;Weight;young adult

PROJECT_TITLE: THE GREAT SMOKY MOUNTAINS STUDY OF RURAL AGING

STUDY_SECTION: SSPB

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


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: BOSTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

ORG_STATE: MA

PHR: PROJECT NARRATIVE Visual attention is a dynamic process, influencing the sensitivity of visual perception at relevant moments in time. The proposed studies will investigate how attention to moments in time influences sensory-level processing in the visual cortex and will elucidate the neural mechanisms underlying voluntary control of attention over time. Improved understanding of these mechanisms will have clinical applications in disorders linked to attentional timing deficits such as ADHD and neglect, as well as in aging populations.

PI_NAMEs: EPSTEIN, MICHAEL LEWIS (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Affect;Aging;Anatomy;Architecture;Area;area striata;Attention;Attention deficit hyperactivity disorder;attentional control;attentional modulation;Behavioral;Brain;Brain Mapping;candidate identification;Cerebellar degeneration;clinical application;clinically relevant;Complex;Computer Models;Cues;Data;design;Disease;Ensure;Experimental Designs;experimental study;extrastriate visual cortex;Functional Magnetic Resonance Imaging;Future;Heterogeneity;Human;imaging modality;Impairment;improved;Individual;interest;Investigation;Link;Literature;Maps;Methods;Modeling;Nature;neglect;neural;neuroimaging;neuromechanism;novel strategies;Pattern;Perception;Population;predictive modeling;Process;Psychophysics;Recovery;Research;Resolution;Resources;response;retinotopic;Role;Sensory;Stimulus;Structure;Temporal Lobe;temporal measurement;Testing;theories;Time;tool;Update;Visual;Visual attention;Visual Cortex;visual information;visual neuroscience;Visual Perception;visual processing

PROJECT_TITLE: Sensory and Control Mechanisms of Temporal Attention


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Kidney Disease;Prevention

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Acute kidney injury requiring dialysis is a devastating complication among hospitalized patients. There are no current interventions to improve recovery of kidney function. Our study seeks to define better recovery- monitoring strategies and better approaches to outpatient dialysis to enable more patients to have renal recovery and to have it sooner, an unequivocally important clinical and patient-oriented outcome.

PI_NAMEs: MCCOY, IAN  (contact)

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;arm;biobank;Biological Markers;Biometry;Board Certification;career;Clinical;clinical practice;Clinical Research;Collection;Complication;Creatinine clearance measurement;Data Collection;Databases;design;Diagnosis;Dialysis procedure;Discrimination;Diuretics;Dose;Dropout;Electrolytes;End stage renal failure;Epidemiology;Event;experience;falls;Family;Fostering;Funding;Goals;Guidelines;Health Care Costs;Hemodialysis;hemodynamics;Hospitalization;Hospitals;Hour;Hypotension;improved;Injury;injury and repair;Injury to Kidney;innovation;Intervention;Intervention Trial;Investigation;K-Series Research Career Programs;Kidney;LCN2 gene;Learning;Life;Life Expectancy;Literature;Manuscripts;Master of Science;Measures;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Metabolic;Monitor;mortality;multi-component intervention;Multicenter Trials;novel;Observational Study;Occupations;Outpatients;participant enrollment;patient oriented research;Patient-Focused Outcomes;Patients;Peer Review;Pilot Projects;pilot trial;prevent;Publishing;Quality of life;Randomized;Randomized, Controlled Trials;Recovery;Recurrence;Renal function;renal ischemia;Renal Replacement Therapy;repaired;Research;Research Infrastructure;Research Personnel;Risk;Safety;safety outcomes;Schedule;skills;Sodium;Spottings;Sum;Temperature;Time;Time trend;timeline;Training;trial enrollment;urinary;Urine;Withdrawal;Work

PROJECT_TITLE: Towards improving recovery from dialysis-requiring acute kidney injury


NIH_SPENDING_CATS: Clinical Research;Genetics;HIV/AIDS;Immunization;Infectious Diseases;Pediatric;Pediatric - AIDS;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: Columbus

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Adolescents represent the largest growing population living with HIV and despite ART, HIV infected individuals have increased morbidity and mortality associated with non-AIDS related complications that are likely driven by persistent inflammation and immune activation. In this project, we seek to develop robust models to elucidate the role of trained immunity in NK cells and monocyte populations in chronic immune activation and dysregulation in perinatally acquired HIV infection that will increase our knowledge of the increased risk of comorbidities in youth and reveal potential areas for targeted interventions and vaccine development.

PI_NAMEs: DIRAJLAL-FARGO, SAHERA ;FUNDERBURG, NICHOLAS T. (contact);LIYANAGE, NAMAL

PROGRAM_OFFICER_NAME: DANG, QUE

PROJECT_TERMS: acute infection;Adherence;Adolescent;Adult;Aging;antiretroviral therapy;Area;Biological;Biological Assay;Cell Physiology;Cells;Cellular Metabolic Process;Child;Chronic;Clinical;co-infection;cohort;Collaborations;comorbidity;cytokine;Cytometry;Data;Development;Environmental Risk Factor;Epigenetic Process;experimental study;Exposure to;Flow Cytometry;Foundations;Functional disorder;gastrointestinal;Gastrointestinal tract structure;Gene Expression Profile;Gene Expression Profiling;Genetic Transcription;geographic difference;gut dysbiosis;high dimensionality;HIV;HIV Infections;HIV-infected adolescents;Immune;immune activation;Immune system;Immune System Diseases;immune system function;Immunity;Immunization;immunoregulation;In Vitro;Individual;Infection;Inflammasome;Inflammation;Inflammatory;Innate Immune System;innovation;Intervention Trial;Knowledge;Leukocytes;Link;Lipids;Lipopolysaccharides;Lymphocyte;Macrophage;Macrophage Activation;Malaria;Measurement;Measures;Mediator;member;Metabolism;microbial;microbial products;Mitochondria;mitochondrial dysfunction;Modeling;monocyte;Morbidity - disease rate;mortality;Myeloid Cells;Natural Immunity;Natural Killer Cells;novel;Participant;pathogen;Pathway interactions;Perinatal;Persons;Pharmaceutical Preparations;Phenotype;polyglucosan;Population;Positioning Attribute;prenatal therapy;Process;prognostic;Prophylactic treatment;Regimen;Reporting;Risk;Role;Signal Transduction;single-cell RNA sequencing;System;T-Cell Activation;therapy development;Toxic effect;Training;Treatment-related toxicity;Trimethoprim-Sulfamethoxazole;Uganda;United States;vaccine development;Youth

PROJECT_TITLE: The role of Trained Immunity and Mitochondrial dysfunction on INnate immunity in children and adolescents aGing with PHIV (TIMING-PHIV)


NIH_SPENDING_CATS: Diabetes;Genetics;Nutrition;Obesity

ORG_CITY: Newark

ORG_DEPT: SURGERY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Type 2 diabetes is caused by insulin resistance and impaired insulin secretion. Elucidating the mechanisms by which CREG1 regulates insulin secretion and action is critical to understanding the pathogenesis of type 2 diabetes and the development of new therapeutic interventions to curb its epidemic.

PI_NAMEs: BUETTNER, CHRISTOPH ;LI, SHAOHUA  (contact)

PROGRAM_OFFICER_NAME: LIANG, HANYU

PROJECT_TERMS: Ablation;adenoviral mediated;Adipose tissue;Adult;Beta Cell;Binding;Biochemical;cell growth regulation;Cell membrane;Cell Physiology;Cell surface;Cells;cellular targeting;Clinical;Complementary DNA;Complex;Consumption;CpG Islands;CRISPR/Cas technology;Databases;Dependovirus;Development;diabetes pathogenesis;Dilution Techniques;DNA methyltransferase inhibition;Down-Regulation;Electron Microscopy;Endocytosis;Endosomes;Enzymes;Epidemic;Exhibits;Exons;Fasting;gain of function;Gene Delivery;Genes;genetic testing;global health;Glucose;Glucose Clamp;Glucose Intolerance;glucose production;Glycoproteins;glycosylation;Goals;Hepatic;Hepatocyte;High Fat Diet;Homeostasis;Human;human subject;Hyperinsulinism;Immunofluorescence Immunologic;Impairment;improved;In Vitro;in vivo;Insulin;insulin granule;Insulin Receptor;insulin regulation;Insulin Resistance;insulin secretion;insulin sensitivity;insulin signaling;Insulin-Like Growth Factor I;Insulin-Like Growth Factor II;Intervention;islet;knock-down;Knock-in Mouse;Knock-out;Knockout Mice;Label;Lead;Link;live cell imaging;Liver;loss of function;mannose 6 phosphate;Mediating;Medical;Membrane;Metabolic;Metabolic Diseases;Methylation;Missense Mutation;Molecular;Mus;Mutagenesis;mutant;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutic intervention;Nutritional;Obese Mice;Obesity;Oligosaccharides;overexpression;Overnutrition;Pancreas;Pathogenesis;Pathway interactions;Perfusion;Physiologic pulse;Physiological;Proinsulin;Protocols documentation;receptor;receptor expression;receptor recycling;Recycling;Regulation;Role;Site;Surface;Surveys;System;Testing;Tissues;Tracer;trafficking;trans-Golgi Network;Vesicle;Wild Type Mouse

PROJECT_TITLE: Role of CREG1 in metabolic homeostasis


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

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

ORG_CITY: GALVESTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Emerging viral diseases threaten human health globally, and West Africa is a source and major epidemic location for many. We will develop a new generation of West African scientists to predict, prevent and contain emerging viral diseases through multidisciplinary scientific and public health training by leveraging the resources of our West African Center for Emerging Infectious Diseases, outstanding research leaders in West Africa, and the exceptional breadth and depth of expertise in emerging viral diseases at the University of Texas Medical Branch (UTMB).

PI_NAMEs: SHEHU, NATHAN YAKUBU;VASILAKIS, NIKOS ;WEAVER, SCOTT C (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Address;Africa;African;Americas;Animal Model;Arboviruses;arthropod-borne;Asia;burden of illness;Chikungunya fever;Circulation;Clinical;Country;data management;Dengue;design;Diagnostic;Disease;Disease Outbreaks;doctoral student;Ebola virus;Education;Emerging Communicable Diseases;emerging virus;Enrollment;Ensure;Epidemic;experience;Generations;Health;Hemorrhage;Hemorrhagic Fever with Renal Syndrome;Human;Laboratory Technicians;Lassa virus;Medical;Methods;Molecular;multidisciplinary;National Institute of Allergy and Infectious Disease;Nigeria;Outcome;Pathogenesis;Phase;Play;prevent;programs;Public Health;Public Health Education;Recording of previous events;Research;Research Training;Risk;Role;Science;Scientist;Sierra Leone;Site;Source;Techniques;Texas;Training;Training Activity;Training Programs;transmission process;Universities;Viral;Viral Hemorrhagic Fevers;Virus;Virus Diseases;Yellow Fever;zika fever;Zoonoses

PROJECT_TITLE: Training and Research on Arboviruses and Zoonoses In Nigeria and Sierra Leone (TRAIN)

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Eye Disease and Disorders of Vision;Infectious Diseases;Neurosciences;Vector-Borne Diseases

ORG_DEPT: BIOLOGY

PHR: NARRATIVE Vision in mosquitoes plays a critical but understudied role in their attraction to hosts. This project will determine the visual features (colors, size, motion) that mosquitoes find attractive and characterize how odor modulates visual responses. This work will also test new visual lures and identify potential molecular targets that compromise the visual and olfactory behaviors to hosts.

PI_NAMEs: AKBARI, OMAR SULTAN;RIFFELL, JEFFREY A (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Aedes;Anopheles Genus;Area;base;Behavior;Behavioral;Behavioral Assay;Biogenic Amine Receptors;Biological Assay;Bite;Blood;Brain;Calcium;Carbon Dioxide;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Color;Color Visions;combat;Coupling;Cues;Culex (Genus);Culicidae;Darkness;Dengue;design;Detection;Development;Disease;Disease Vectors;Environmental Wind;experimental study;Eye;Flying body movement;food resource;Future;Gene Targeting;Generations;Genetic;genetic approach;Genome engineering;Goals;Human;Image;Insect Vectors;Insecta;insight;Intervention;Knock-out;Link;Malaria;Mediating;Methods;Modality;Molecular Genetics;Molecular Target;Mosquito Control;Motion;mutant;Mutate;neural;neuromechanism;Neuromodulator;Neurons;neurophysiology;neuroregulation;novel;Octopamine;octopamine receptor;Odors;Opsin;Optic Lobe;Oranges;Paper;Partner in relationship;pathogen;Photoreceptors;Play;preference;Process;Publishing;receptor;response;Rhodopsin;Role;Searching Behavior;Sensory;Skin;Smell Perception;Source;SW opsin;Testing;Time;tool;Tsetse Flies;United States Department of Agriculture;vector mosquito;Vision;Visual;visual information;Visual Motion;visual search;Visual System;water vapor;Work;ZIKA

PROJECT_TITLE: Olfactory modulation of color vision and behavior in mosquitoes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-J(03)]


NIH_SPENDING_CATS: Aging

ORG_CITY: WASHINGTON

ORG_NAME: HOWARD UNIVERSITY

ORG_STATE: DC

PHR: Program Director/Principal Investigator (Last, First, Middle): Duttaroy, Atanu  Project narrative Howard University's Advancing Diversity in Aging Research (HUADAR) program is successfully engaged in providing structured, mentored, hands-on research and educational experiences on aging to underrepresented minority students. This application is requesting for a renewal of this program. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

PI_NAMEs: DUTTAROY, ATANU  (contact)

PROGRAM_OFFICER_NAME: CARTER, CHRISTY

PROJECT_TERMS: addiction;African American;Age;age-related disease;Aging;aging population;aging related;apprenticeship;Bachelor's Degree;Biological;Biology;Biomedical Research;California;career;Career Choice;Caring;Certification;Clinical Research;college;Degree program;Development;Disease;Doctor of Philosophy;Education;Educational Activities;Educational Curriculum;Elderly;Enrollment;Environment;Evaluation;Exercise;experience;Faculty;Fostering;Foundations;Future;Gerontology;Goals;graduate school;Graduation Rates;hands on research;Health;Human Resources;innovation;Institution;interest;Knowledge;Laboratories;Learning;lectures;Longevity;Managed Care;medical specialties;meetings;Mental Health;Mentors;Minority;minority scientist;National Institute on Aging;notch protein;Outcome Measure;Persons;Physiology;Principal Investigator;Process Measure;programs;Publishing;recruit;Reporting;Research;Research Institute;Research Personnel;Research Support;Research Training;responsible research conduct;retention rate;Rotation;Schools;Self Care;Services;skills;social;social cohesion;Social isolation;social media;Societies;Structure;Students;summer research;supportive environment;Surveys;symposium;Time;Training;Translating;Trauma;undergraduate research;undergraduate student;underrepresented minority student;United States;Universities;Work;Writing

PROJECT_TITLE: Advancing aging research through development of minority Gerontologists


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

ORG_CITY: HOUSTON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Estrogen receptor-positive (ER+) breast cancer comprises 70 of all breast cancer cases and primarily metastasizes to bone, but there have not been suitable mammalian models that mimic the progression of this disease, which greatly hinders the research effort to understand this subtype of breast cancer and to develop new and effective therapeutics. In our preliminary studies, we have established novel rat models of ER+ breast cancer that mimic human ER+ breast cancer formation and metastasis. In this application, we will characterize these models in detail and credential them for investigating human ER+ breast cancer development, progression and treatment.

PI_NAMEs: LI, YI  (contact);ZHANG, XIANG

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: Adjuvant;adjuvant endocrine therapy;Behavior;Biological;Biological Markers;bisphosphonate;bone;Brain;Breast Cancer Cell;Breast Cancer gene;breast cancer metastasis;Breast Cancer Model;Breast Cancer Patient;cancer initiation;cancer subtypes;Cell Line;Characteristics;Circulation;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complement;Credentialing;Data;Development;Disease;Disease Progression;drug candidate;Drug Modelings;Drug Targeting;Ductal Epithelial Cell;Epithelium;Estrogen receptor positive;Event;Excision;Exclusion;experimental study;Genetic;Genetically Engineered Mouse;Goals;Histopathology;hormone therapy;Human;Immune;Immune system;Immunocompetent;Immunodeficient Mouse;In Vitro;in vivo;Injections;Intervention;Investigation;Knowledge;Laboratories;Learning;Lesion;Liver;Lung;lymph nodes;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Marrow;Metastatic Neoplasm to the Bone;Metastatic/Recurrent;Micrometastasis;Modeling;Molecular;Molecular Profiling;Mus;Mutation;Neoplasm Metastasis;neoplastic cell;next generation;NF1 gene;novel;novel therapeutics;Oncogenes;Operative Surgical Procedures;Organ;Osteoclasts;Patients;Penetrance;PIK3CA gene;Population;premalignant;Prevalence;Prevention;Prevention strategy;Primary Neoplasm;Process;Property;Proteome;RAS genes;Rattus;Refractory;Research;Resistance;resistance mechanism;Resources;Risk;Role;SDZ RAD;Series;Signal Transduction;single-cell RNA sequencing;Site;Specimen;standard of care;Study models;Survival Rate;Therapeutic;therapeutically effective;therapy resistant;TP53 gene;transcriptomics;treatment response;tumor;tumor initiation;Tumor Suppressor Proteins;tumorigenesis;tumorigenic;Virus;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Next Generation Rat Models of ER+ Breast Cancer


ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE DNAJC13, which encodes Receptor-Mediated Endocytosis 8 (RME8), is a synaptically enriched co- chaperone that functions in clathrin-mediated transport and membrane recycling. Here, we will characterize the role of RME8 in Parkinsonism.

PI_NAMEs: CHANDRA, SREEGANGA S (contact)

PROGRAM_OFFICER_NAME: SIEBER, BETH-ANNE

PROJECT_TERMS: Affect;Age;Age Months;age related;Aging;alpha synuclein;Attention;Autophagosome;Auxilins;Behavioral;Behavioral Assay;behavioral phenotyping;Binding;Brain;Brain Diseases;Clathrin;Clathrin-Coated Vesicles;Corpus striatum structure;Data;Deposition;design;dopaminergic neuron;Dorsal;Early Endosome;Electron Microscopy;endosome membrane;Endosomes;Equilibrium;Essential Genes;Evaluation;Exhibits;experimental study;Gene Expression;Genes;Genotype;Hand Strength;Heterogeneity;Human;Human Cell Line;Impairment;in vivo;insight;knock-down;Lead;Link;LoxP-flanked allele;Mediating;Membrane;Membrane Protein Traffic;Modeling;Molecular;Molecular Chaperones;Motor;motor behavior;motor deficit;motor disorder;motor symptom;mouse model;Mus;mutant;Mutation;Nerve;Nerve Degeneration;nestin protein;Neurodegenerative Disorders;neuron loss;Neurons;neuropathology;novel;Organelles;Parkinson Disease;Parkinsonian Disorders;Pathologic;Pathology;Pathway interactions;Patients;Performance;Phosphorylation;Protein Family;Proteins;Publishing;receptor;receptor for advanced glycation endproducts;receptor function;receptor mediated endocytosis;Recycling;Research;Role;Sampling;single nucleus RNA-sequencing;single-cell RNA sequencing;Sorting;Substantia nigra structure;Surveys;Synapses;Synaptic Vesicles;SYNJ1 gene;Testing;Therapeutic Intervention;therapeutic target;trafficking;trans-Golgi Network

PROJECT_TITLE: Investigating the Functions of RME8 in Parkinson's Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AN-B(02)M]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY

PHR: Segregating recessive variants are responsible for a substantial health burden. The work proposed here  interrogates the recessive effects of 2.4 million polymorphic sites segregating in an experimental  nematode panel derived from six genomes freshly sampled from the wild. The data will generate  generalizable gene- and variant-scale models that predict whether variants are likely to have recessive  effects.

PI_NAMEs: ROCKMAN, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: WETTERSTRAND, KRIS A

PROJECT_TITLE: EDGE CMT: deleterious recessive variation - from experimental data to predictive models


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Hematology;Human Genome;Orphan Drug;Precision Medicine;Rare Diseases

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Advances in the treatment of hematologic malignancies have been disappointing. The ECOG-ACRIN Leukemia Translational Science Center will create, support, and synergize partnerships between clinical and laboratory investigators and foster the continuous, near-term translation of state-of-the art laboratory studies into the clinical context to improve outcomes for leukemia patients.

PI_NAMEs: ABDEL-WAHAB, OMAR ;LEVINE, ROSS L (contact)

PROJECT_TERMS: Acceleration;Acute leukemia;American College of Radiology Imaging Network;Biological Assay;Biological Markers;Biology;biomarker discovery;Caring;Center for Translational Science Activities;Chronic Leukemia;Classification;CLIA certified;Clinic;Clinical;clinical care;Clinical Investigator;clinical practice;Clinical Trials;Clinical Trials Design;Communities;computing resources;Correlative Study;Credentialing;Data;data warehouse;Development;Diagnostic Procedure;Disease;Eastern Cooperative Oncology Group;Ensure;epigenetic profiling;Fostering;Funding;gene discovery;genomic platform;genomic profiling;Genomics;Goals;Hematologic Neoplasms;Hematopoietic Neoplasms;Immunotherapy;improved outcome;Infrastructure;innovation;insight;Laboratories;Laboratory Finding;Laboratory Research;Laboratory Scientists;Laboratory Study;Lead;Leadership;leukemia;leukemia tissue bank;leukemia treatment;Molecular;molecular oncology;Molecular Profiling;Monitor;National Clinical Trials Network;new therapeutic target;novel;novel marker;novel therapeutic intervention;novel therapeutics;Outcome;Pathogenesis;Patients;personalized diagnostics;Phase;Pilot Projects;pre-clinical research;predicting response;Productivity;prognostic;programs;Protocols documentation;Relapse;Research;Research Design;Research Personnel;Resistance;resistance mechanism;Resources;response;Risk;risk stratification;Sampling;Science;standard of care;synergism;System;targeted treatment;Technology;Testing;Therapeutic;Translating;Translational Research;translational study;Translations;Treatment Efficacy;treatment stratification

PROJECT_TITLE: ECOG-ACRIN Integrated Leukemia Translational Science Center (LTSC)


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Osteoporosis;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_NAME: NEW YORK GENOME CENTER

PHR: PROJECT NARRATIVE Human genetics research has found that nucleotide variants can influence traits and diseases. However, the function of these variants and the genes through which they act remains difficult to identify when they do not directly map to a gene. This project aims to identify the genes that these variants influence by developing modular workflows integrating large-scale genetic association studies and genome engineering in cell models, providing insight into the function of these these variants that underly traits and diseases.

PI_NAMEs: MORRIS, JOHN ALLAN (contact)

PROGRAM_OFFICER_NAME: PAZIN, MICHAEL J

PROJECT_TERMS: Automobile Driving;base editing;base editor;Biological Assay;Biology;Blood;bone;bone cell;Bone Density;Bone Diseases;career;Catalogs;causal variant;Cell model;Cell surface;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Committee Members;Complex;Complex Genetic Trait;CRISPR screen;Cytosine;Data;Development;Disease;Drug Targeting;Educational process of instructing;Environment;Epigenetic Process;Erythroid Progenitor Cells;flexibility;Foundations;functional genomics;Gene Expression;Gene Expression Regulation;Genes;genetic association;Genetic Engineering;Genetic Research;genetic variant;Genome;Genome engineering;genome wide association study;genomic data;Grant;Haplotypes;Hematological Disease;Human;Human Genetics;improved;insight;Interdisciplinary Study;job market;K-562;Lead;Link;Linkage Disequilibrium;Literature;Location;Machine Learning;Maps;Measurement;Mentors;Mentorship;method development;Methods;mineralization;Modeling;multimodality;Mutation;network dysfunction;new therapeutic target;New York;novel;Nucleotides;Osteoblasts;Osteoporosis;Phase;Phenotype;Positioning Attribute;programs;Proteins;Regulatory Element;Research;Research Project Grants;Selection Criteria;Signal Transduction;single cell sequencing;Statistical Methods;stem cell model;student mentoring;symposium;Testing;therapeutic candidate;therapeutic target;Training;Training Programs;trait;Untranslated RNA;Variant;Writing

PROJECT_TITLE: Linking GWAS variants to function with single-cell pooled CRISPR screens

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM-G]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Cancer;Climate-Related Exposures and Conditions;Genetics;Prevention;Skin Cancer

ORG_DEPT: DERMATOLOGY

PHR: Project Narrative For this grant, we will catalogue the mutational factors shaping melanocytes in normal human skin. Completion of these studies will address major gaps in knowledge needed to understand the etiology of melanoma, guide strategies to prevent melanoma, and inform molecular strategies to slow down the evolution of melanoma.

PI_NAMEs: SHAIN, ALAN HUNTER (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Address;Affect;Aging;Anatomy;Area;Automobile Driving;Back;Base Pairing;Biological;Biological Assay;Cancer Etiology;cancer genomics;cancer risk;Cataloging;Catalogs;Cell division;Cells;Chronic;Communities;Complement;Complex;course development;Data;DNA Damage;DNA Repair;DNA sequencing;epidemiology study;Etiology;Evolution;expectation;experience;Exposure to;Face;Genes;Genome;Genomics;Genotype;Goals;Grant;Guide prevention;Guidelines;Head and neck structure;Human;Human body;In Vitro;Incidence;Individual;innovative technologies;insight;Knowledge;Laboratories;Malignant Neoplasms;Measures;melanocyte;Melanoma;Methods;Molecular;Mutagens;Mutation;Normal tissue morphology;Observational epidemiology;Observational Study;Occupational Exposure;Organ;Pattern;Periodicals;Persons;Pigments;preneoplastic cell;prevent;Prevention;Prevention strategy;Process;Public Health;Radiation Induced DNA Damage;Recording of previous events;Recreation;repaired;Reporting;Research;Research Personnel;Resolution;Risk;Risk Factors;Role;Sensitivity and Specificity;Shapes;Shoulder;Site;Skin;Skin Cancer;Somatic Mutation;Sun Exposure;Sunbathing;Testing;the sun;tissue/cell culture;tumor;ultraviolet irradiation;Ultraviolet Rays;UV induced;UV Radiation Exposure

PROJECT_TITLE: The mutational mechanisms shaping melanocytes in human skin

STUDY_SECTION: ACTS

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


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Childhood Leukemia;Genetics;Hematology;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The enzyme Dot1L drives overexpression of oncogenes that are essential for the initiation and progression of mixed lineage leukemia, an aggressive subset of acute leukemias with no known cure and limited effective clinical treatments. Here we illustrate the molecular basis for Dot1L activity by identifying the interfaces between Dot1L and its nucleosome substrate that are essential for oncogene activation by Dot1L. By establishing the disease-relevance of these Dot1L-nucleosome interaction interfaces in mixed lineage leukemia, this work will inform the development of novel targeted therapeutics to combat this deadly disease.

PI_NAMEs: SPANGLER, CATHERINE JEANETTE (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Acute leukemia;AMPA Receptors;Automobile Driving;Binding;Cell Differentiation process;Cell Line;Cell Survival;Cells;Chimeric Proteins;Chromosomal translocation;Clinical;Clinical Treatment;combat;Complex;Cryoelectron Microscopy;Deposition;Development;Disease;Drug Targeting;Enzymes;Epigenetic Process;epigenetic regulation;Foundations;Gene Expression;Genes;Genetic;genetic regulatory protein;Genetic Transcription;Glioblastoma;Histone H2B;Histone H3;histone methylation;histone methyltransferase;histone modification;Histones;Homeobox Genes;improved;In Vitro;insight;Knowledge;leukemia;Leukemic Cell;leukemogenesis;Lysine;Maintenance;Malignant Neoplasms;Mammalian Cell;member;Methylation;Methyltransferase;mixed lineage leukemia cell;Mixed-Lineage Leukemia;MLL gene;Modification;Molecular;Mutate;Mutation;new therapeutic target;Normal Cell;novel;novel strategies;Nucleosomes;Oncogene Activation;Oncogenes;Oncogenic;Outcome;overexpression;Pathway interactions;Phase;Post-Translational Protein Processing;Postdoctoral Fellow;pre-clinical;promoter;Protein Biochemistry;Protein Chemistry;protein complex;Proteins;recruit;Regulator Genes;Reporting;Research;Resolution;RNA Polymerase II;Role;Site;Site-Directed Mutagenesis;structural biology;Structure;targeted treatment;therapeutic development;therapeutic target;tool;Transcription Elongation;Transcription Initiation;Transcription Regulatory Protein;Transcriptional Activation;tumorigenesis;Ubiquitin;Up-Regulation;Variant;Work

PROJECT_TITLE: Characterization of native AMPA receptor structure and function in glioblastoma


ADMINISTERING_IC: HD

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

ORG_CITY: DETROIT

ORG_DEPT: PHYSIOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative Intraflagellar transport (IFT), originally discovered in Chlamydomonas, is also essential for the assembly and maintenance of most eukaryotic cilia and flagella, and defects in IFT cause several human genetic diseases. The proposed studies will explore the unique roles of the IFT25 complex in construction of the sperm accessory structures that are required for normal sperm function. The proposed studies will not only fill a gap in our knowledge of the process of IFT in spermiogenesis, but also reveal a different role of the IFT25 complex in germ cells and somatic cells during ciliogenesis and build a platform on which to study the roles of other IFT components in male and female reproduction.

PI_NAMEs: ZHANG, ZHIBING  (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: A kinase anchoring protein;Affect;alpha helix;Binding;Carrier Proteins;Categories;cellular imaging;Chlamydomonas;Cilia;ciliopathy;cilium biogenesis;cilium motility;Co-Immunoprecipitations;comparative;Complex;conditional knockout;Cyclic AMP-Dependent Protein Kinases;Dedications;Defect;Development;Disease;dynactin;Dynein ATPase;Dyskinetic syndrome;Female;Flagella;Genes;Genetic Diseases;Genotype;Germ Cells;Human;Human Genetics;in vivo;Infertility;interest;Knock-in Mouse;Knockout Mice;Knowledge;Laboratories;Link;Maintenance;male;Male Infertility;Mass Spectrum Analysis;Mediating;Monitor;Morphogenesis;Motor;Movement;Mus;mutant mouse model;Mutant Strains Mice;Mutation;particle;Peptide Hydrolases;Phenotype;Phosphorylation;Polycystic Kidney Diseases;Process;Protein Kinase;Protein Precursors;protein protein interaction;Proteins;Proteomics;Reproduction;Research;Retinal Degeneration;Role;signal peptide peptidase;Signal Transduction;Somatic Cell;sperm cell;sperm function;sperm protein;Sperm Tail;Spermatocytes;Spermatogenesis;Spermiogenesis;Sterility;Structure;System;Testing;Testis;Time;Tissues;trafficking;Transmission Electron Microscopy

PROJECT_TITLE: Intraflagellar transport (IFT) and sperm formation

STUDY_SECTION: CMIR

STUDY_SECTION_NAME: Cellular, Molecular and Integrative Reproduction Study Section[CMIR]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: PROJECT NARRATIVE This proposal seeks to address the unmet need for computational tools capable of analyzing emerging spatial genomic datasets in particular in complex tissues. We aim to develop interpretable and rigorous machine learning models to propel characterization of diverse cell types, their spatial organization and interactions, and their underlying gene circuitry from combining transcriptomic, proteomic, epigenomic and imaging datasets. Our tools will be impactful in understanding the role of the microenvironment and cell-cell crosstalk in a wide range of normal and disease tissue types.

PI_NAMEs: AZIZI, ELHAM  (contact)

PROGRAM_OFFICER_NAME: GAO, JEAN XUEJING

PROJECT_TERMS: Address;analytical tool;Area;ATAC-seq;Bayesian learning;biological systems;Brain;brain tissue;Cell Communication;cell type;Cells;Chromatin;Collaborations;Communities;Complex;computer framework;Computer Models;Computer software;computerized tools;Computing Methodologies;Data;Data Analyses;data integration;data modalities;Data Set;Dependence;design;Development;Disease;Disease Progression;Dissociation;Dropout;Embryo;Embryonic Development;Environment;epigenomics;experience;explainable machine learning;flexibility;Foundations;functional genomics;Future;Gene Expression;Gene Expression Profile;gene regulatory network;generative models;Genes;genetic manipulation;Genome;genomic data;Genomic Segment;Genomics;Glioblastoma;Goals;high dimensionality;histological image;Histology;Human;Image;In Situ;innovation;insight;Joints;Knowledge;Location;machine learning framework;machine learning method;machine learning model;Malignant Breast Neoplasm;Maps;Measurement;Messenger RNA;Methods;Modeling;Molecular;Morphologic artifacts;multidimensional data;multimodal data;Multiomic Data;Mus;Mutation;Neighborhoods;neuropsychiatric disorder;Noise;Normal Range;novel;open source;Organoids;Outcome;Pattern;Physiology;programs;Proteins;Proteomics;Regulation;Research;Resolution;Role;Spatial Distribution;spatial integration;Statistical Models;supervised learning;System;Techniques;Technology;Tissue imaging;Tissues;Tonsil;tool;transcriptome sequencing;transcriptomics;user friendly software;Work

PROJECT_TITLE: Machine learning methods for interpreting spatial multi-omics data


ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE The Department of Pediatrics at Boston Children's Hospital is dedicated to the training of physician-scientists and helping them develop into world-class independent scientists and future leaders in the field. We have a strong track record of training physician-scientists who have gone on to make fundamental discoveries in basic and translational research, which have had a lasting impact on the treatment of pediatric disease. The Child Health Research Career Development Award program has played an integral role in our ability to support the development of physician-scientists at our institution and we propose to continue and strengthen this program over the next five years.

PI_NAMEs: CHUNG, WENDY K (contact)

PROGRAM_OFFICER_NAME: WINER, KAREN

PROJECT_TERMS: Advisory Committees;Area;Basic Science;Boston;Brain;career;career development;Child Health;Childhood;Development;Developmental Biology;Disease;Eligibility Determination;Ensure;Epilepsy;Faculty;Fellowship;Funding;Genetic;Genomics;Goals;Grant;host-microbe interactions;Immunology;Institution;instructor;Investigation;K-Series Research Career Programs;Kidney Diseases;Laboratories;member;Mentored Clinical Scientist Development Program;Mentors;Mentorship;Molecular;Mucous Membrane;novel therapeutics;Pediatric Hospitals;pediatrician scientist;Positioning Attribute;professor;programs;Research;research and development;Scientist;Self-Examination;Supervision;Training;Translational Research;United States National Institutes of Health;Work

PROJECT_TITLE: Child Health Research Career Development Award (CHRCDA) Program (K12)


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Patient Safety

ORG_CITY: ANN ARBOR

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Approximately 60,000 general anesthetics are performed in the U.S. daily, the majority of which require the administration of intravenous vasopressors to counteract general anesthesia-induced cardiovascular depression and low blood pressure (hypotension). Over the past decade, the harmful effects of intraoperative hypotension, including myocardial injury, stroke and acute kidney injury have been repeatedly observed, and vasopressor therapies to treat intraoperative hypotension, specifically the choice between norepinephrine and phenylephrine, are debated vigorously. The proposed series of studies utilize a multicenter network of medical centers to better understand vasopressor selection and use and conduct a pilot trial to inform development of a future multicenter pragmatic clinical trial to assess the impact of vasopressor selection on end-organ perfusion outcomes.

PI_NAMEs: JANDA, ALLISON MARY (contact)

PROGRAM_OFFICER_NAME: REDMOND, NICOLE

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Adherence;Adoption;Adult;Affect;Anesthesia procedures;Anesthesiology;Attitude;Board Certification;Cardiac;Cardiovascular system;career;chronic pain;Clinical;Clinical Informatics;Clinical Trials;Clinical Trials Design;Data;Data Collection;design;Development;Discipline of obstetrics;Doctor of Philosophy;Echocardiography;Electronic Health Record;Fatigue;Fellowship;Functional disorder;Future;General Anesthesia;General anesthetic drugs;Goals;Health;Hospitals;Hypotension;improved;indexing;Information Systems;Institution;Intensive Care Units;International;Interview;Intravenous;intravenous administration;Investigation;knowledge base;Learning;Lung;Medical center;Medicine;member;Mental Depression;Mentors;Methods;Michigan;Myocardial;myocardial injury;Norepinephrine;Operating Rooms;Operative Surgical Procedures;Organ;organ injury;Outcome;Outcomes Research;Patient Care;Patients;Pattern;Perfusion;Perioperative;Perioperative Care;Peripheral;Phenylephrine;Physiological;Pilot Projects;pilot trial;Postoperative Period;Pragmatic clinical trial;pragmatic study;pragmatic trial;Precision Medicine Initiative;Procedures;prospective;protocol development;Protocols documentation;Provider;randomized, clinical trials;Research;Research Methodology;Research Personnel;Research Technics;Retrospective Studies;risk minimization;Safety;Sampling;Scientist;Series;Site;skills;Stroke;Structure;Surveys;Testing;therapy design;Training;United States National Institutes of Health;Universities;Variant;Vasoconstrictor Agents

PROJECT_TITLE: PHEnylephrine versus NOrepinephrine in Major NONcardiac surgery (PHENOMeNON): Foundational Studies for a Pragmatic Randomized Clinical Trial.

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(OA)]


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: PROJECT NARRATIVE Medulloblastoma (MB) is a highly aggressive embryonal tumor of the cerebellum for which safer and more effective therapies are urgently needed. The developmental basis of molecularly and clinically distinct MB subgroups remains ill-defined, hampering the generation of accurate disease models required for mechanistic understanding and preclinical evaluation. This proposal will discover developmental origins of poorly characterized MB subgroups, and experimentally credential transcriptional dependencies defining subgroup identity as a novel therapeutic vulnerability in high-risk patients.

PI_NAMEs: NORTHCOTT, PAUL  (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: Acute;Affect;Area;Atlases;Automobile Driving;biological heterogeneity;Biology;Brush Cell;Cells;Cerebellar Neoplasms;Cerebellum;Chemistry;Child;Childhood Cerebellar Neoplasm;Clinical;clinical heterogeneity;Clustered Regularly Interspaced Short Palindromic Repeats;Consensus;Coupled;Credentialing;Data Set;Dependence;Development;Developmental Biology;Diagnosis;Disease;disease model;effective therapy;Epigenetic Process;Exhibits;fetal;Fostering;Future;Generations;Genes;Genetic Transcription;Genomics;Glutamates;high risk;Human;improved;improved outcome;innovation;insight;interdisciplinary approach;Investigation;Knowledge;Lead;lens;Life;Link;Lip structure;Literature;Longevity;Maintenance;Malignant - descriptor;Malignant Childhood Neoplasm;Malignant Neoplasms;Maps;Medulloblastoma;medulloblastoma cell line;Molecular;Molecular Profiling;molecular targeted therapies;mortality;mouse model;multidisciplinary;Mus;Mutation;Nature;Neuronal Differentiation;new therapeutic target;next generation;novel;novel therapeutics;Oncogenic;overexpression;Pathogenesis;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Population;pre-clinical;Pre-Clinical Model;preclinical evaluation;progenitor;programs;Proliferating;protein degradation;Quality of life;Regulator Genes;Relapse;Reporting;Research;Research Personnel;scaffold;Science;SHH gene;single cell genomics;Study models;Subgroup;Synthetic Genes;Testing;Therapeutic;transcription factor;transcriptome;tumor;Tumor Biology;tumorigenesis;Validation

PROJECT_TITLE: Mapping the Cerebellar Origins of Medulloblastoma Subgroups

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_CITY: Princeton

ORG_DEPT: CHEMISTRY

ORG_NAME: PRINCETON UNIVERSITY

PHR: Project Narrative  In this proposal, we demonstrate that flavin-dependent enzymes are versatile and catalytically promiscuous enzymes, capable of effecting synthetically valuable free radical reactions with high yields and enantioselectivity. This work provides a solution to a long-standing and important challenge in the chemical synthesis and will serve as the bedrock on which new synthetic methods are developed for the construction of medicinally relevant molecules. These new reactions and catalysts will provide biomedical sciences with new tools to expedite the design and manufacture of medicines and biological probes, creating significant benefit to human health.

PI_NAMEs: HYSTER, TODD KURT (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Development of Flavoproteins as Catalysts for Asymmetric Radical Reactions

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Clinical Research;Genetics;Human Genome;Mental Health;Mental Illness

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative / Relevance Now in its 13th year, the Psychiatric Genomics Consortium is perhaps the most innovative and productive experiment in the history of psychiatry. We propose to expand the work of the PGC so we can learn key lessons about the fundamental basis of major psychiatric disorders

PI_NAMEs: NIEVERGELT, CAROLINE M;SEBAT, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Acceleration;Address;Affect;Alleles;base;biobank;Biological;Biology;Biotechnology;career;case control;Cells;Clinical;Collaborations;Communication;Communities;Country;Data;Diagnostic;digital media;Disease;DNA Resequencing;education resources;Educational Materials;Ensure;Epidemiology;exome;exome sequencing;experimental study;Facebook;Family;Fostering;functional genomics;Funding;Genes;Genetic;genetic architecture;genetic pedigree;Genetic Variation;Genets;Genome;genome sequencing;genome wide association study;genomic data;genomic locus;Genomics;Goals;improved;Individual;Industry;innovation;insight;Institution;instrument;Investments;Journals;Knowledge;Learning;Life;Maps;Measures;Medical;Medicine;Mendelian randomization;Mental disorders;Meta-Analysis;Methods;Mission;Modeling;Molecular;National Institute of Mental Health;Nature;Neurosciences;novel;novel therapeutics;Outcome;outreach;Paper;patient stratification;patient subsets;Patients;Phase;Phenotype;predict clinical outcome;Productivity;Psychiatric Diagnosis;psychiatric genomics;Psychiatry;rare variant;Recording of previous events;Reproducibility;Research Personnel;Resistance;Resources;Risk;Risk Factors;Science;Scientist;severe psychiatric disorder;Source;statistics;success;Symptoms;Therapeutic;therapeutic development;Time;translational potential;Twitter;Update;Variant;whole genome;Work;working group

PROJECT_TITLE: 4/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-B(02)]


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

PHR: A specific modification, named acylation, of the gastric hormone ghrelin is important for its function in the regulation of food intake. This proposal will investigate how the mechanistic target of rapamycin controls the acylation of ghrelin, leading to subsequent alteration in liver lipid. The information generated from this project will provide new insights relevant to treatment strategies for liver steatosis.

PI_NAMEs: SEELEY, RANDY J (contact)

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: Acylation;Acyltransferase;Adult;Affect;American;Binding;Biological;Body Weight decreased;Cells;Cirrhosis;Data;Deposition;des-n-octanoyl ghrelin;design;Development;Eating;energy balance;Event;Fatty Liver;Food Intake Regulation;FRAP1 gene;Gene Expression;Genes;ghrelin;GHS-R1a;Goals;Health;Hepatic;Hepatocyte;High Fat Diet;Hormones;Hypothalamic structure;insight;Kupffer Cells;lipid metabolism;Lipids;Liver;Mediating;Modification;Mus;Names;Neurons;non-alcoholic fatty liver disease;novel;novel therapeutic intervention;Nutrient availability;Obesity;Organism;Pathogenesis;Pathway interactions;Primary carcinoma of the liver cells;Production;receptor;Regulation;Role;Signal Pathway;Signal Transduction;Site;Societies;Steatohepatitis;Stomach;Techniques;Testing;Time;transcription factor;Transgenic Mice;Transgenic Organisms;treatment strategy;Triglycerides;Variant

PROJECT_TITLE: The mTOR-ETV5 signaling in gastric X/A like cells and its role in hepatic lipid metabolism and steatosis

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


NIH_SPENDING_CATS: American Indian or Alaska Native;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Patient Safety;Racial and Ethnic Minority Health Research;Rural Health

ORG_CITY: OKLAHOMA CITY

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR

ORG_STATE: OK

PHR: Relevance Statement This proposal is directly relevant to public health. As a Lead Academic Participating Site in the National Clinical Trials Network (NCTN), the Stephenson Cancer Center will directly contribute to the design and conduct of NCTN clinical trials for newly developed therapies, including multi-modality treatments, combinations of novel agents, Precision Medicine screening, and advanced imaging approaches. The overall goal is to improve cancer patient outcomes and reduce the burden of cancer for all populations, with an emphasis on underserved populations in Oklahoma.

PI_NAMEs: MOORE, KATHLEEN N. (contact);TAKEBE, NAOKO

PROGRAM_OFFICER_NAME: MOONEY, MARGARET M

PROJECT_TERMS: Address;Advisory Committees;American College of Radiology Imaging Network;American Indian Population;American Indians;anti-cancer research;Authorship;Cancer Burden;cancer care;Cancer Center;cancer clinical trial;cancer health disparity;Cancer Patient;career development;clinical care;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Network;Combined Modality Therapy;data management;data submission;design;Direct Costs;Disease;Eastern Cooperative Oncology Group;Education;Eligibility Determination;Enrollment;Ensure;experience;Extramural Activities;Faculty;Funding;Goals;Grant;Health Sciences;imaging approach;improved;Incidence;Informatics;Information Dissemination;innovation;Knowledge;knowledge base;Lead;Leadership;Malignant Neoplasms;meetings;member;Molecular;mortality;multidisciplinary;National Clinical Trials Network;novel;Office Management;Oklahoma;Oncology;operation;organizational structure;Outcome;participant enrollment;patient navigation;patient navigator;Patient-Focused Outcomes;Patients;Phase;Play;Population;precision medicine;programs;protocol development;Public Health;Publications;quality assurance;Randomized;Research;Research Activity;Research Design;Research Infrastructure;Research Personnel;Resources;Role;Rural;screening;Site;Social Workers;Source;Southwest Oncology Group;standard of care;statistical center;Structure;therapy development;Time;Training;Underinsured;Underrepresented Populations;Underserved Population;Uninsured;Universities;Voting;Work;working group

PROJECT_TITLE: A Lead Academic Participating Site in Oklahoma for the Design and Conduct of NCTN Clinical Trials


NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Childhood Injury;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Stroke;Unintentional Childhood Injury

ORG_CITY: SEATTLE

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE This proposal details work to investigate an FDA-approved drug (azithromycin) that has significant promise as a neuroprotective agent, using a ferret model of premature brain injury. As nearly 10% of infants are born prematurely, with outcomes including increased risks of behavioral and cognitive problems, severe disability, and even death, neuroprotective agents for infants born preterm remain a significant clinical need. The ferret has a gyrified brain that develops postnatally and is very similar to the human brain in terms of both development and structure, making it ideal for investigating premature brain injury.

PI_NAMEs: WOOD, THOMAS  (contact)

PROGRAM_OFFICER_NAME: PILEGGI, ANTONELLO

PROJECT_TERMS: 37 weeks gestation;Adult;Aftercare;Animal Model;Animals;Antibiotics;Antiinflammatory Effect;Asthma;Azithromycin;behavior test;Behavioral;behavioral outcome;Birth;Blood - brain barrier anatomy;Brain;Brain Hypoxia-Ischemia;Brain Injuries;Cardiovascular Diseases;Cell Death;Cells;Cerebrovascular Disorders;Cessation of life;Childhood;Chronic;Clinical;Clinical Trials;clinically relevant;Cognitive;Communities;Complex;deprivation;Development;disability;Disease;DNA;Dose;Drug Delivery Systems;Drug Kinetics;Drug Targeting;Encephalopathies;Epigenetic Process;Erythropoietin;Extremely low gestational age newborn;FDA approved;Ferrets;Fluorescence-Activated Cell Sorting;glial activation;Glucose;Glutathione;Health;high risk population;Histologic;Human;Hyperoxia;Hypertension;Hypotension;Hypoxia;Hypoxic-Ischemic Brain Injury;Image;Immunohistochemistry;immunoregulation;improved;improved outcome;In Vitro;Infant;Infection;Inflammation;Inflammatory;Inflammatory Response;injured;Injury;insight;Ischemia;Ischemic Brain Injury;Laboratories;Lipid Peroxidation;Lipopolysaccharides;Live Birth;Long-Term Effects;Macrolides;Macrophage;Magnetic Resonance Imaging;Metabolic syndrome;Microglia;migration;Modeling;Morbidity - disease rate;mortality;Motor;Myeloid Cells;Neonatal;Neonatal Mortality;Nervous System Trauma;Neurocognitive Deficit;Neurodevelopmental Impairment;neuroprotection;Neuroprotective Agents;Newborn Infant;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Outcome;oxidation;oxidative damage;Oxidative Stress;Oxygen;Pathology;Patient-Focused Outcomes;Perinatal;Phagocytes;Pharmaceutical Preparations;Phenotype;Placenta;Populations at Risk;postnatal;Pregnancy;Pregnant Women;premature;Premature Birth;Premature Infant;Preterm brain injury;Publishing;Rattus;Resource-limited setting;Risk;Rodent;Rodent Model;Schizophrenia;Shotgun Sequencing;Site;Slice;Spinal cord injury;Stroke;stroke model;Structure;Survivors;transcriptome;transcriptome sequencing;white matter;Work

PROJECT_TITLE: Repurposing Azithromycin for premature brain injury


NIH_SPENDING_CATS: Cancer;Immunotherapy;Lung;Lung Cancer

ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: PROJECT NARRATIVE This project will investigate the role of Sirt2, a protein involved in regulating metabolism of T lymphocytes that mediate immune responses against cancer. We will explore this problem by analyzing mice deficient in Sirt2 or its partner molecules as well as genetically engineered human T lymphocytes isolated from lung cancer and melanoma patient tumor samples. Our studies may guide development of novel strategies to improve metabolic fitness of T lymphocytes, and thus enhance the capacity of these cells to elicit effective immune defense against cancer.

PI_NAMEs: KIM, SUNGJUNE  (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Acetylation;aerobic glycolysis;Aging;Animals;Attention;Beds;cancer cell;cancer immunotherapy;Cancer Patient;cancer therapy;Cell Physiology;Cells;Cellular Metabolic Process;Citric Acid Cycle;clinical translation;combinatorial;CTAG1 gene;Data;Deacetylase;Deacetylation;Development;effector T cell;Endowment;Enzymes;exhaustion;fatty acid metabolism;fatty acid oxidation;frontier;Genes;Genetic Engineering;Genetic study;Glucose;Glutamine;Glycolysis;Histone Deacetylase;Human;Human Engineering;Immune;immune checkpoint;immune function;Immune response;Immune Targeting;Immunologics;immunoregulation;Immunotherapeutic agent;Immunotherapy;immunotherapy clinical trials;Impairment;improved;In Vitro;in vivo;Infiltration;inhibitor;Laboratories;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Melanoma;Melanoma patient;Memory;Metabolic;metabolic fitness;Metabolism;metabolomics;Modeling;Molecular;Molecular Biology;Molecular Genetics;Mus;neoplastic cell;Nivolumab;Non-Small-Cell Lung Carcinoma;novel;novel strategies;overexpression;Oxidative Phosphorylation;Patients;pharmacologic;Phenotype;Phosphorylation;Physiological;Post-Translational Protein Processing;potential biomarker;predicting response;pressure;programs;Proliferating;Protein Acetylation;Proteins;Proteomics;Reproducibility;Resistance;response;Resveratrol;Role;Sampling;Signal Transduction;T cell regulation;T-Cell Activation;T-Cell Development;T-Lymphocyte;Testing;Treatment Efficacy;tumor;Tumor Escape;Tumor Immunity;tumor microenvironment;ubiquitin-protein ligase;Up-Regulation

PROJECT_TITLE: Role of Sirt2 in T Cell Metabolism

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


NIH_SPENDING_CATS: Contraception/Reproduction;Infertility

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE The proposed research will provide new frameworks for the treatment of male infertility, a major public health concern, and identify targets for male contraception. Spermatozoa acquire motility and fertilizing power during their transit through the epididymis, a long tube located downstream of the testis. Our laboratory studies how epithelial cells work together with immune cells to protect spermatozoa against pathogens and autoimmunity and contribute to the immune- privileged environment of the epididymis. Thus, the proposed research is relevant to NIH’s mission to enhancing health and reducing illness.

PI_NAMEs: BATTISTONE, MARIA AGUSTINA (contact)

PROJECT_TERMS: 3-Dimensional;Ablation;Address;Animals;Antigens;Autoimmune;Autoimmune Responses;Autoimmunity;Bacterial Antigens;Bioinformatics;Biology;Cell Communication;cell injury;Cell Separation;cell type;Cells;chemokine;Clear Cell;Communication;Confocal Microscopy;CX3CL1 gene;CXCL10 gene;Data;Development;Diphtheria Toxin;Disease;Duct (organ) structure;Eating;Environment;Epididymis;Epididymitis;Epithelial Cells;Epithelium;Equilibrium;Flow Cytometry;FOXP3 gene;Genes;Goals;Health;human male;Immune;immune activation;Immune response;Immune system;Immune Tolerance;Immunology;immunoregulation;Infection;Inflammation;Inflammatory Response;Injections;Injury;innovation;insight;interdisciplinary approach;Knowledge;Laboratory Study;Ligands;Macrophage;Maintenance;male;Male Contraceptive Agents;Male Infertility;Mediator;microorganism;Mission;monocyte;Mononuclear;Motility;mouse model;Mucosal Immunity;Mucous Membrane;Mus;Neutrophil Infiltration;novel;novel therapeutics;Partner in relationship;pathogen;Pathogenicity;Pathway interactions;Phagocytes;Play;Positioning Attribute;prevent;Protons;Public Health;receptor;recruit;Regulatory T-Lymphocyte;Reproductive Biology;Reproductive Health;Reproductive Physiology;Research;response;Role;Specialized Epithelial Cell;sperm cell;Sperm Maturation;Spermatic Cord Torsion;Sterility;stressor;Structure of thyroid parafollicular cell;Surveys;System;Techniques;Testis;Torsion;transcriptome sequencing;transcriptomics;Transforming Growth Factor beta;Transgenic Mice;Tryptophan 2,3 Dioxygenase;Tube;Tubular formation;United States National Institutes of Health;Work

PROJECT_TITLE: Proton-secreting epithelial cells as key modulators of epididymal mucosal immunity.


NIH_SPENDING_CATS: Genetics;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative The stem cells that maintain sperm production in mammals are difficult to grow in the laboratory dish. This study addresses how molecular switches within these cells enable external growth signals from outside the cell to be processed appropriately. The ultimate goal is to develop new ways to identify and expand the sperm-forming stem cells.

PI_NAMEs: EVANS, TODD R (contact);LIU, YING

PROJECT_TERMS: Ablation;Address;Adult;Biochemical;Biosensor;Cell Culture System;Cells;Clone Cells;Data;DUSP6 protein;Equilibrium;experimental study;Feedback;FGF2 gene;Fibroblast Growth Factor;Future;Gene Family;Genes;Genetic;Genetic Diseases;Genetic Transcription;Genetically Engineered Mouse;Germ Cells;glial cell-line derived neurotrophic factor;Goals;Growth;Growth Factor;Growth Factor Receptors;Hyperactivity;Image;Impairment;improved;In Vitro;in vivo;Infertility;Kinetics;Laboratories;Mammals;MAP Kinase Gene;Measurement;member;Methodology;Molecular;mouse model;Mus;novel;Outcome;Pathway interactions;Phenotype;Physiological;Population;preservation;prevent;Process;Production;real time monitoring;Recovery;Regulation;Reporter;response;Role;self-renewal;Series;Signal Induction;Signal Transduction;single-cell RNA sequencing;Specificity;sperm cell;Spermatogonia;stem cell biomarkers;stem cell differentiation;stem cell function;stem cell niche;stem cell self renewal;Stem cell transplant;stem cells;Structure;System;Testing;Testis;therapeutic target;Time;Translating;Transplantation;Up-Regulation;Work

PROJECT_TITLE: Negative feedback regulation of growth factor signaling in adult spermatogonial stem cells


NIH_SPENDING_CATS: Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;HIV/AIDS;Infectious Diseases;Microbiome;Neurosciences;Pediatric;Pediatric - AIDS;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention

ORG_CITY: RONDEBOSCH

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: UNIVERSITY OF CAPE TOWN

PHR: NARRATIVE Infants who are exposed to HIV in utero but uninfected (iHEU) are at higher risk for poorer neurodevelopmental outcomes compared to their HIV-unexposed counterparts, yet the role of fetal exposure to differing maternal antiretroviral therapy (ART) regimens and associated biological mechanisms remain underexplored. Here, we propose to leverage prospectively collected data and stored specimens from the Surveillance Monitoring for ART Toxicities (SMARTT) study within the Pediatric HIV/AIDS Cohort Study (PHACS) network to assess meconium microbiome composition and function and systemic inflammation, and associations with neurodevelopment among iHEU with fetal exposure to different maternal ART regimens. This study has the potential to identify biological mechanisms of poor neurodevelopment among iHEU, and to inform novel intervention strategies for this growing, vulnerable population.

PI_NAMEs: HAPPEL, ANNA-URSULA  (contact)

PROGRAM_OFFICER_NAME: ESBER, ALLAHNA LAUREN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adult;Affect;Anti-Retroviral Agents;antimicrobial;antiretroviral therapy;Area;Bacteria;Biological;Birth;Breast Feeding;co-infection;cognitive function;cohort;comorbidity;cytokine;Data;design;Development;early childhood;Emotional;Event;Exposure to;fetal;fetal programming;Guidelines;gut bacteria;gut microbiome;gut microbiota;Health;high risk;HIV;human data;Immune;immune activation;Immune response;Immune system;Immunology;improved;in utero;Individual;infancy;Infant;Inflammation;Inflammatory;inhibitor;insight;Integrase;Intervention;Investigation;Language;Life;life span;Link;maternal microbiome;Measures;Meconium;Mediating;microbial;microbiome;microbiome composition;Monitor;Morbidity - disease rate;Mothers;neurodevelopment;Neurologic;Neurotransmitters;novel;Outcome;Participant;Pediatric HIV/AIDS Cohort Study;Pharmaceutical Preparations;Play;Population;postnatal;pre-exposure prophylaxis;Pregnancy;prenatal;prenatal exposure;Property;prospective;Protease Inhibitor;Recommendation;Regimen;Reporting;repository;Research;Research Infrastructure;Research Training;Risk;Role;Sampling;social;Specimen;System;systemic inflammatory response;Testing;Treatment Protocols;Treatment-related toxicity;Vaginal delivery procedure;Vulnerable Populations;Woman;World Health Organization

PROJECT_TITLE: Influence of fetal antiretroviral exposure on gut microbiota, systemic inflammation and neurodevelopment in infants exposed to HIV


ORG_CITY: BALTIMORE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Disruption of circadian rhythm, which are biological processes that oscillate with a period of 24 hours, has been linked to increased cancer risk in night-shift workers. Cancer cells can have disrupted cellular circadian clocks that could make them more or less aggressive, or resistant to therapy. This unexplored research area, which is likely to contribute to a better understanding of resistance to standard and immunotherapy, will be the focus of this application, which is expected to provide concepts for better therapeutic strategies.

PI_NAMEs: DANG, CHI V. (contact)

PROJECT_TERMS: Acceleration;Address;Affect;anti-PD-1;anti-PD1 therapy;Area;ARNTL gene;Biological Markers;Biological Models;Biological Process;Biological Rhythm;Biology;cancer cell;cancer risk;CD8-Positive T-Lymphocytes;Cell Line;Cells;chemokine;circadian;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;comparison control;Coupled;CRISPR/Cas technology;cytokine;cytotoxic CD8 T cells;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;Diurnal Rhythm;Dominant-Negative Mutation;Doxycycline;Drosophila genus;Ectopic Expression;Engineering;Exclusion;exhaustion;Fasting;feeding;Gene Expression;Genes;Growth;Heterogeneity;Hour;Human;Human Engineering;humanized mouse;Immune;immune reconstitution;immune resistance;Immune signaling;Immunity;Immunocompetent;Immunologics;immunoregulation;Immunotherapy;in vivo;Infiltration;Inflammation;Inflammatory;Interferons;Intermittent fasting;Knock-out;Link;Malignant Neoplasms;Melanoma;Melanoma Cell;Melanoma Tumor;Metabolic;Metabolism;metabolome;Modeling;Molecular;monocyte;mouse model;Mus;Mutation;novel;Null Lymphocytes;Oncogenic;Patients;Phenocopy;Polycomb;Prognosis;programmed cell death ligand 1;Proteins;Proteome;Reagent;reconstitution;Research;Resistance;response;Role;Series;shift work;Signal Transduction;Sleep;System;T cell infiltration;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic;therapy resistant;transcription factor;transcriptome;transcriptome sequencing;treatment response;tumor;Tumor Biology;tumor heterogeneity;Tumor Immunity;tumor progression;tumorigenesis;vector;virtual

PROJECT_TITLE: Defining the Role of the Cancer Circadian Clock in Tumor Immunity and Tumorigenesis


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

PHR: Project Narrative We will continue the effort to promote the development of novel yet practical solutions for important privacy and security challenges in human genomic research, via organizing genomic privacy/security competitions and workshops, with emphasis on engaging/supporting researchers from nationally underrepresented groups to participate in our competitions and attend the workshops.

PI_NAMEs: JIANG, XIAOQIAN ;KUO, TSUNG-TING  (contact);TANG, HAIXU

PROGRAM_OFFICER_NAME: SEN, SHURJO KUMAR

PROJECT_TERMS: Academia;Acceleration;Address;Benchmarking;biomedical informatics;Biomedical Research;Caring;Code;Communities;Companions;computer science;Consent;cryptography;Data;Data Set;data sharing;Development;Educational workshop;Evaluation;Event;Extravasation;Family;Fellowship;Fingerprint;frontier;Funding;Future;Genome;genomic data;Genomics;Grant;Human;Human Genome;human genomics;Individual;Industry;innovation;Institution;interdisciplinary collaboration;interest;Knowledge;large scale data;Measures;meetings;Methods;Modeling;National Human Genome Research Institute;Nature;new technology;news;novel;Outsourcing;Paper;Participant;Patients;Performance;Postdoctoral Fellow;posters;preference;Privacy;privacy preservation;Privatization;prototype;Publications;Reporting;Research;Research Personnel;Research Project Grants;Rest;Risk;Secure;Security;Series;Side;Slide;Speech;Students;success;Surveys;task analysis;Technology;Testing;Time;tool;Travel;Underrepresented Minority;Underrepresented Populations;Voting;web portal;Woman

PROJECT_TITLE: iDASH Genome Privacy and Security Competition Workshop


NIH_SPENDING_CATS: Biotechnology;Genetics;Neurosciences

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Ion channels play a fundamental role in the function of brain neurons, and ion channel mutations are associated with neurological and psychiatric disorders. As such the localization and function of brain ion channels is highly regulated. We have discovered a novel mode of ion channel regulation whose properties and functional impact form the focus of this proposal.

PI_NAMEs: DICKSON, EAMONN JAMES;SANTANA, LUIS F (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Ablation;Action Potentials;Animals;Biophysics;Brain;Cell membrane;Consensus;Coupled;Coupling;CREB1 gene;Cytoplasm;Data;Dendrites;Dendritic Spines;Dependence;Disease;Endoplasmic Reticulum;Event;experimental study;Functional disorder;Gene Expression;gene therapy;Genes;Genetic Transcription;Health;high resolution imaging;Hippocampus;Image;Intervention;Ion Channel;Kv2.1 channel;L-Type Calcium Channels;Mediating;Mediator;Membrane;Mental disorders;Modeling;Molecular;Molecular Analysis;multimodality;mutant;Mutation;Nervous System Disorder;Neurodegenerative Disorders;Neurodevelopmental Disorder;neuronal cell body;Neurons;neurotransmission;novel;nuclear factors of activated T-cells;Phenotype;Play;Population;Potassium Channel;Property;protein complex;Proteins;Proteomics;Regulation;response;Role;Ryanodine Receptor Calcium Release Channel;Shapes;Signal Pathway;Signal Transduction;Site;skills;Structure;Synaptic plasticity;System;Testing;Transcript;transcription factor;voltage;voltage gated channel;Work

PROJECT_TITLE: Neuronal Kv2.1 Potassium Channels as Organizers of Somatic L-Type Calcium Channel Microdomains

STUDY_SECTION: NTRC

STUDY_SECTION_NAME: Neurotransporters, Receptors, and Calcium Signaling Study Section[NTRC]