NIH_SPENDING_CATS: Biotechnology;Cancer;Eye Disease and Disorders of Vision;Genetics;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: PROJECT NARRATIVE (Relevance Statement): We have developed the first spontaneous human retinoblastoma tumor model by using iPSCs from patients with germline RB1 mutations. Using this model combined with our extensive collection of orthotopic patient- derived xenografts we will determine if retinoblastoma tumorigenesis is a multistep process and study the clonal evolution and selection of tumor cells during treatment.

PI_NAMEs: DYER, MICHAEL A (contact)

PROGRAM_OFFICER_NAME: LIU, ZHIHUI

PROJECT_TERMS: 3-Dimensional;Address;Affect;Age;Alleles;Basic Science;Benign;Bilateral;Biology;Biometry;cancer genetics;Cancer Model;Cells;chemotherapy;Child;Chromatin;Clinic;Clinical Research;Clinical Trials;Clonal Evolution;Collection;Data;Disease;DNA Methylation;Epidemiology;Evaluation;Experimental Models;Eye;Eye Enucleation;Family;Family member;forging;Frequencies;Future;Gene Expression;Genetic;Genetic Heterogeneity;Genetic study;Germ Lines;Goals;Government;Head;Heterozygote;high risk;Human;improved;in vivo;Individual;innovation;insight;Knowledge;Laboratories;Lesion;Link;Loss of Heterozygosity;Maintenance Therapy;Malignant - descriptor;Malignant Childhood Neoplasm;Malignant Neoplasms;mathematical model;Medicine;Modeling;Molecular;Monitor;multidisciplinary;Mutation;MYCN gene;neoplastic cell;No Evidence of Disease;novel;Nucleotides;Oncogene Activation;Oncogenes;Oncology;Organoids;Outcome;Pathology;patient derived induced pluripotent stem cells;patient derived xenograft model;Patients;Penetrance;Peripheral;Persons;Preclinical Testing;preservation;prevent;Process;RB1 gene;RB1 Gene Inactivation;Reagent;Research;Research Proposals;Resolution;Resources;Retina;Retinoblastoma;Screening for cancer;stem cell biology;stem cell organoids;Survivors;SYK gene;Testing;tool;Treatment Failure;Treatment Protocols;treatment response;tumor;tumor progression;tumor xenograft;Tumor-Associated Process;tumorigenesis;Vision

PROJECT_TITLE: Modeling Retinoblastoma Initiation Using 3D-Retinal Organoids

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: Veterans Affairs

ORG_CITY: SAN ANTONIO

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM

ORG_STATE: TX

PHR: By 2030, it is estimated that around 76 million people will have osteoporosis in the U.S. This holds significant implications for Veteran healthcare because nearly three-quarters (72.3%) of the patients served by the VA are over 50 years old, while at the same time, the size of the VA population over the age of 65 is projected to double in size over the next 30 years. The purpose of this renewal application is to address whether replenishing the matricellular protein Cyr61/CCN1Cyr61 to the aging bone matrix will restore the ability of the MSC microenvironment (niche) to rejuvenate old MSC self-renewal, differentiation, and bone formation capacity. The information gained from the proposed studies will provide great benefit to both the veteran and general population by developing a new approach for treating osteoporosis that focuses on restoring the aging stem cell niche.

PI_NAMEs: CHEN, XIAO-DONG  (contact)

PROJECT_TERMS: Address;Age;age related;Age-Related Bone Loss;Aging;Animal Model;Apoptosis;Architecture;Attenuated;attenuation;Binding;Biological Assay;BMP2 gene;bone;Bone Density;bone loss;Bone Marrow;bone marrow mesenchymal stem cell;bone mass;Bone Matrix;Bone Tissue;Cells;comparative efficacy;cyr61 protein;Data;Defect;double walled carbon nanotube;efficacy evaluation;Exhibits;Extracellular Matrix;Funding;General Population;Genetic;Goals;Healthcare;Home;Human;human old age (65+);Immunodeficient Mouse;Impairment;improved;In Vitro;in vivo;Incubated;innovation;Knock-out;Knockout Mice;Measures;Metabolism;Methods;military veteran;mouse model;Mus;novel;novel strategies;old mice;Osteoblasts;Osteoclasts;Osteocytes;Osteogenesis;Osteopenia;Osteoporosis;overexpression;Patients;Persons;Population;Positioning Attribute;Property;Proteins;Proteomics;Recombinants;Rejuvenation;Reporting;response;Role;self-renewal;side effect;stem cell aging;stem cell function;stem cell niche;stem cells;stemness;Stromal Cells;Testing;Time;Veterans;Wild Type Mouse

PROJECT_TITLE: Reversing Age-related Bone Loss by Administration of the Matricellular Protein Cyr61/CCN1


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: NEW YORK

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

ORG_STATE: NY

PHR: This project will address the need for improved therapies for advanced well differentiated/dedifferentiated liposarcoma (DDLS), a rare cancer that generally does not respond to chemotherapy. We will evaluate the effectiveness of the combination of palbociclib, a drug that targets a genetic change characteristic of DDLS, with INCMGA0012, an investigational drug that de-inhibits immune responses against the tumor. We will also search for molecular indicators (biomarkers) of benefit from this combination to select the best patients to receive this treatment in the future, and, to better understand how the drugs interact, investigate the relationship between palbociclib induced growth arrest and antitumor immune responses.

PI_NAMEs: D'ANGELO, SANDRA P (contact)

PROGRAM_OFFICER_NAME: RUBIO, TERESA

PROJECT_TITLE: Identifying senescence and immune biomarkers predictive of benefit to combined CDK4 and checkpoint blockade inhibition in patients with dedifferentiated liposarcoma


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Diabetes;Nanotechnology

ORG_CITY: DAVIS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: Project Narrative . Nanoscale organization of proteins is emerging as a critical process controlling cell function in health and disease. The long-term goal of this study is to examine mechanisms underlying the spatial nano-organization and activity of a key protein involved in the regulation of smooth muscle cells that make up the arterial wall during physiological conditions and during elevations in extracellular glucose and diabetes. The study fulfills relevant public health goals and NIH mission by generating fundamental basic knowledge that could help identify and develop novel treatment strategies to address vascular complications during diabetes.

PI_NAMEs: NAVEDO, MANUEL F (contact)

PROGRAM_OFFICER_NAME: CATANIA, SELEN MURATOGLU

PROJECT_TERMS: A kinase anchoring protein;Active Biological Transport;Acute;Address;Adrenergic Agents;Amino Acids;Animal Model;Animals;Arteries;Biochemistry;Blood flow;Blood Pressure;Blood Vessels;C-terminal;Calcineurin;Cell Nucleus;Cell Physiology;cell type;Cells;Chemosensitization;Chronic;Complex;Coupled;Coupling;Cyclic AMP-Dependent Protein Kinases;Data;Development;Diabetes Mellitus;diabetic patient;Diffusion;Disease;Dissociation;Electrophysiology (science);experimental study;Exposure to;extracellular;Fostering;Foundations;Gene Expression;Glucose;Goals;Health;health goals;Human;hypertensive;in silico;innovation;Ion Channel;Knowledge;Lasers;Lateral;Mediating;Membrane;Membrane Proteins;Microscopy;Mission;Modeling;Molecular;Mus;Muscle Cells;Myography;nano;nanoscale;Nanoscopy;Neurons;non-diabetic;novel;novel therapeutic intervention;Optics;particle;patch clamp;Pathology;Phosphorylation;Phosphorylation Site;Physiological;Physiology;Play;pressure;Process;Proteins;Public Health;Regulation;response;Risk Factors;Role;Signal Pathway;Signal Transduction;Site;Smooth Muscle Myocytes;Source;Surface;Techniques;Testing;Therapeutic;tool;trafficking;transcription factor NF-AT c3;treatment strategy;United States National Institutes of Health;vasoconstriction;Vesicle;voltage;Work

PROJECT_TITLE: Coupling of vascular CaV1.2 channels in health and disease

STUDY_SECTION: IVPP

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


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Clinical Research;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Mental Illness;Neurosciences;Psychosis

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Neuropsychiatric manifestations are common in Rare Genetic Disorders (RGDs), affecting brain development and functioning throughout the lifespan; copy number variants (CNVs) at 22q11.2 and 16p11.2 loci are among the most common RGDs impacting developmental psychopathology. We propose to capitalize on highly informative samples and integrate prospective dimensional and categorical phenotyping with whole genome sequencing across these reciprocal CNVs. This work will identify convergent risk mechanisms for developmental neuropsychiatric disorders that have relevance to the broader population.

PI_NAMEs: BEARDEN, CARRIE E (contact)

PROGRAM_OFFICER_NAME: MEINECKE, DOUGLAS L

PROJECT_TERMS: 16p11.2;22q11.2;adverse outcome;Affect;Algorithms;Anxiety;Anxiety Disorders;Architecture;Attention;Attention deficit hyperactivity disorder;Attentional deficit;autism spectrum disorder;Behavior;Brain;case control;Clinical;clinical diagnosis;clinical phenotype;clinical predictors;Cognition;Cognitive;cohort;Collaborations;Complement;Complex;Computing Methodologies;Copy Number Polymorphism;Data;Development;Developmental Course;Developmental Delay Disorders;Diagnosis;Dimensions;Disease;Early Intervention;Emotional;Emotions;Environment;Environmental Risk Factor;Evaluation;experience;externalizing behavior;Family;Family member;gene environment interaction;Genetic;genetic architecture;Genetic Determinism;genetic pedigree;Genetic Predisposition to Disease;Genetic study;genetic variant;genome resource;genome sequencing;genome wide association study;genomic locus;Genomics;Goals;Heterogeneity;Hyperactivity;Individual;Institution;Intellectual functioning disability;interest;International;Knowledge;large scale data;life span;Literature;Measures;Memory;Mental Depression;model building;Modeling;Molecular;National Institute of Mental Health;Nature;neurobehavioral;Neurocognition;neuropsychiatric disorder;neuropsychiatry;Online Systems;Outcome;Patients;personalized approach;phenomics;Phenotype;polygenic risk score;Population;Positioning Attribute;processing speed;prospective;Psychiatric Diagnosis;Psychopathology;Psychoses;Public Domains;rare genetic disorder;rare variant;recruit;Recurrence;Risk;risk prediction model;Sampling;Schizophrenia;social;Social Behavior;Specificity;symptomatology;Symptoms;Syndrome;theory of mind;tool;Variant;whole genome;Work

PROJECT_TITLE: 3/9 Dissecting the effects of genomic variants on neurobehavioral dimensions in CNVs enriched for neuropsychiatric disorders


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: SAINT LOUIS

ORG_DEPT: PATHOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: NARRATIVE The proposed studies address a gap in understanding of how an emerging class of resistance enzymes, identi- fied in a growing number of human-associated settings, have the potential to severely compromise treatment of bacterial pathogens. The proposed research will identify new avenues for detection and intervention which are relevant to public health, because current treatment options for increasingly drug resistant bacteria are failing. This project is relevant to the NIH's mission of developing fundamental knowledge that may reduce the burden of human disease.

PI_NAMEs: DANTAS, GAUTAM  (contact);WENCEWICZ, TIMOTHY ADAM

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Address;analog;Antibiotic Resistance;Antibiotics;Bacteria;Base Sequence;Binding;Binding Sites;Biochemical;Bioinformatics;Biological;Biological Assay;Cells;Clinical;clinically relevant;cofactor;Color;combat;crosslink;design;Detection;Development;Diagnostic;Disadvantaged;Distal;DNA Shuffling;drug resistant bacteria;Elements;Enzyme Kinetics;Enzymes;Evolution;experimental study;Family;fitness;Flavins;Funding;Generations;Genes;Genetic;Human;human disease;Human Microbiome;human pathogen;improved;In Vitro;Infection;inhibitor;innovation;interest;Intervention;Isotope Labeling;Knowledge;Ligand Binding;Maps;markov model;Mediating;Methods;Mission;Mixed Function Oxygenases;Modification;Molecular;Morbidity - disease rate;mortality;Motivation;mouse model;multi-drug resistant pathogen;multidisciplinary;Mutagenesis;novel;Outcome;oxidation;pathogen;pathogenic bacteria;Pharmaceutical Preparations;Phenotype;Plasmids;Population;pressure;Proteins;Public Health;rapid detection;rational design;Reporter;Reporting;Research;Resistance;resistance mechanism;Ribosomes;scaffold;Site;small molecule;small molecule inhibitor;Soil;Structure;Testing;Tetracycline Resistance;Tetracyclines;Therapeutic;transmission process;Treatment Failure;United States National Institutes of Health;Validation;Variant;X-Ray Crystallography

PROJECT_TITLE: Structural, mechanistic, & evolutionary characterization of tetracycline destructases

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: Chicago

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Functional intrinsic optical signal (IOS) imaging, also termed as optoretinography (ORG) or optophysiology, promises a high-resolution method for noninvasive, objective assessment of retinal physiology. This study is to validate functional IOS imaging of stimulus-evoked light changes correlated with the activation phase of phototransduction, which can advance early disease diagnosis and prompt treatment evaluation of age- related macular degeneration (AMD), retinitis pigmentosa (RP) and other eye conditions that are known to cause photoreceptor dysfunctions. 1

PI_NAMEs: YAO, XINCHENG  (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: Age;Age related macular degeneration;Anatomy;Animal Model;awake;Biological Markers;Biophysical Process;biophysical properties;Blindness;Clinical;clinical application;clinical translation;comparative;Cone;Consumption;cost;Custom;Darkness;design;Detection;Diabetic Retinopathy;Disease;disease diagnosis;Early Diagnosis;Early treatment;Electron Microscopy;Evaluation;Eye;Eye diseases;Foundations;Functional disorder;Functional Imaging;Fundus photography;Grant;Human;human subject;Hybrids;Image;imaging platform;In Vitro;in vivo;Individual;insight;Length;Light;light microscopy;Maps;Measurement;meter;Methods;millisecond;Morphology;mouse model;Mus;Ophthalmoscopes;Ophthalmoscopy;Optical Coherence Tomography;Optics;Phase;Photoreceptors;Phototransduction;Physiological;Physiology;prevent;Process;quantitative imaging;recruit;Resolution;response;Retina;Retinal Cone;Retinal Degeneration;retinal imaging;Retinal Photoreceptors;retinal stimulation;Retinitis Pigmentosa;Rhodopsin;Rod;Sagittaria;Signal Transduction;Solid;Source;Stimulus;Structure;success;superresolution imaging;temporal measurement;Testing;therapy outcome;Time;Tissues;ultra high resolution;Vertebrate Photoreceptors;virtual;Visible Radiation

PROJECT_TITLE: Functional imaging of retinal photoreceptors


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Infectious Diseases;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Project Narrative Cytomegalovirus (CMV) is prevalent in humans and has been implicated in the malignant brain tumor glioblastoma (GBM) and other cancers. We have developed a novel murine model of CMV in GBM and identified for the first time potential molecular and cellular mechanisms by which CMV can accelerate tumor growth and alter responses to therapy. Therefore, in this project we will use this model alongside human GBM samples from patients with known CMV status to further understand the biology of CMV in GBM and assess new approaches to improve GBM treatment with the goal of rapid translation to the clinic.

PI_NAMEs: COOK, CHARLES H;LAWLER, SEAN EDWARD (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: Acceleration;Address;Adjuvant Therapy;Affect;angiogenesis;Anti-viral Agents;Anti-viral Therapy;antiviral immunity;Area;Autologous Dendritic Cells;Automobile Driving;Biology;Biometry;blood vessel development;Blood Vessels;Brain Neoplasms;CD8-Positive T-Lymphocytes;chemoradiation;Chemosensitization;chemotherapy;Clinic;Clinical;Clinical Treatment;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;cooking;Cytomegalovirus;Cytomegalovirus Infections;Cytomegalovirus Vaccines;Data;Dedications;defined contribution;Diagnosis;differential expression;Disease;experience;experimental study;Future;Genes;Glioblastoma;Goals;Growth;Herpesviridae;Human;human data;Immune;Immunity;Immunocompetent;Immunoglobulin G;Immunology;Immunotherapy;Impairment;improved;improved outcome;in vivo;knock-down;Link;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Modeling;Molecular;mouse model;Mus;mutant;neoplastic cell;novel;novel strategies;Nucleic Acids;Operative Surgical Procedures;Outcome;Patient-Focused Outcomes;Patients;Pattern;Pericytes;Phenotype;Platelet-Derived Growth Factor;prevent;Primary Brain Neoplasms;Progression-Free Survivals;Proteins;Publishing;Radiation;recruit;Reporting;Research Personnel;Resistance;resistance mechanism;response;Role;Sampling;seropositive;standard of care;Survival Rate;Survivors;T cell infiltration;temozolomide;Therapeutic;therapeutic target;therapeutically effective;Time;transforming virus;Translations;Treatment outcome;treatment response;treatment strategy;tumor;tumor growth;tumor microenvironment;tumor progression;Up-Regulation;Valganciclovir;Viral;Virus;Virus Replication;YY1 Transcription Factor

PROJECT_TITLE: Defining the role of cytomegalovirus in glioblastoma therapies

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Brain Disorders;Mental Health;Mental Illness;Schizophrenia;Serious Mental Illness

ORG_CITY: BALTIMORE

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Project Narrative The goal of the proposed program is to prepare MDs, PhDs and PharmDs for a career in translational research in mental health with a focus on schizophrenia and psychosis-related disorders. MPRC research engages a broad range of integrated and translational science including; neurophysiology, neuroimaging, basic neurochemistry, circuitry modeling in rodents and miniature pigs, disease etiology, domains of psychopathology and endophenotypes, neurocognition, experimental therapeutics and clinical trials. This competitive five-year renewal application proposes to leverage our previous success and continue to improve our training approach to produce productive, well-rounded, translationally-focused scientists.

PI_NAMEs: CARPENTER, WILLIAM T.;ELMER, GREGORY I (contact);KELLY, DEANNA L

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TITLE: Multidisciplinary Schizophrenia Research Training


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Genetics;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BIRMINGHAM

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Project Narrative To better understand the causes of complex neurological birth defects and disorders in humans, there is a need to resolve the effects of key signaling pathways on system-wide stem cell interactions and neuronal differentiation in vivo over broad segments of a neuronal population’s developmental timeline. We will directly analyze in vivo data at high spatiotemporal resolution, without reducing biological complexity, to understand and predict multicellular behavior in the developing vertebrate olfactory epithelium. Our work will determine broadly applicable mechanisms of stem cell migration and neurogenesis, including how two progenitor cell types interact with each other and other cell types to coordinate the assembly of a diverse neuronal population.

PI_NAMEs: SAXENA, ANKUR  (contact)

PROGRAM_OFFICER_NAME: STEIN, KATHRYN K

PROJECT_TERMS: Address;Algorithms;Behavior;Biological;Biological Models;cell behavior;Cell Communication;cell motility;cell type;Cells;Complex;Congenital Abnormality;Cues;Data;Defect;Development;Disease;Endocrine;experimental study;Feedback;Genes;Genetic;genetic manipulation;Genetic Programming;Heat-Shock Response;Human;in vivo;intercellular communication;Investigation;Ligands;Link;Location;Mediating;migration;Modeling;Molecular;Mus;Nature;Neural Crest;Neural Crest Cell;neurogenesis;Neurologic;Neuronal Differentiation;Neurons;Notch and Wnt Signaling Pathway;notch protein;Notch Signaling Pathway;novel;Olfactory Epithelium;olfactory neurogenesis;Olfactory Pathways;olfactory sensory neurons;Output;Pathway interactions;Pattern;Phenotype;Pituitary Gland;Play;Population;Process;receptor;Resolution;Retina;Role;Secondary to;Sensory;Signal Pathway;Signal Transduction;spatiotemporal;Specific qualifier value;Specificity;stem cell migration;stem cell population;stem cells;System;Techniques;temporal measurement;Testing;Time;timeline;Tissues;tool;transcription factor;Vertebrates;WNT Signaling Pathway;Work;Zebrafish

PROJECT_TITLE: Resolving Spatiotemporally-Specific Multicellular Dynamics In Vivo During Olfactory Neurogenesis

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Drug Abuse (NIDA only);Prevention;Substance Misuse

ORG_CITY: UNIVERSITY PARK

ORG_DEPT: MISCELLANEOUS

ORG_NAME: PENNSYLVANIA STATE UNIVERSITY, THE

ORG_STATE: PA

PHR: PROJECT NARRATIVE Substance use and addiction persist as systemic public health problems; preventing them will improve the nation’s health, yet successful prevention is complex. The proposed interdisciplinary training program will produce a new generation of behavioral scientists who are experts in conducting rigorous, responsible, innovative research on the prevention of substance use and addiction. By integrating prevention science and innovative methods, these prevention scientists will be leaders in preventing harmful substance use and reducing social, disease, and economic burdens.

PI_NAMEs: LANZA, STEPHANIE T;MAGGS, JENNIFER L (contact)

PROGRAM_OFFICER_NAME: GOLDSTEIN, AMY B

PROJECT_TERMS: Methodology;Prevention;Training

PROJECT_TITLE: Prevention and Methodology Training


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Nutrition

ORG_CITY: DURHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE In a previously performed study, healthy persons were randomly assigned to two years of reducing calorie intake or continuing eating as usual. Results showed the low calorie group had superior benefits in multiple areas of aging-related health. Samples and data from this project remain available for additional studies to better understand calorie reduction effects. This proposal describes a plan to make the best possible use of these samples and data and also develop new investigators and projects in the area of aging.

PI_NAMEs: HUFFMAN, KIM M. (contact);KRAUS, WILLIAM E;PIEPER, CARL F

PROGRAM_OFFICER_NAME: DUTTA, CHHANDA

PROJECT_TERMS: Address;Aging;aging related;Ancillary Study;Area;biobank;Biological;biological age;Biological Process;Biology of Aging;Caloric Restriction;Calories;Capsicum;career development;Caring;Clinical Research;Collaborations;Complex;complex data;Coupled;Data;data integration;data repository;Databases;design;Development;dietary;Discipline;Drug Targeting;Eating;Educational workshop;Energy Intake;Ensure;Epigenetic Process;experience;Fellowship;Fostering;Funding;Genetic;Grant;Growth;Health;Human;Infrastructure;Insecta;Intake;interdisciplinary collaboration;Intervention;Investigation;Knowledge;life span;Long-Term Effects;Maintenance;Mediator;member;metabolomics;nonhuman primate;Organ;Organism;Persons;phenotypic data;Pilot Projects;Process;programs;Proteomics;Publications;Randomized;Randomized, Controlled Trials;repository;Research;Research Infrastructure;Research Institute;Research Personnel;Resources;response;Review Committee;Rodent;Sampling;Scholars Program;secondary analysis;support network;System;Systems Biology;Tissues;transcriptomics;trial design;U-Series Cooperative Agreements;United States National Institutes of Health;Universities;web site;working group;Yeasts

PROJECT_TITLE: ENHANCING THE CALERIE NETWORK TO ADVANCE AGING BIOLOGY

STUDY_SECTION: NIA

STUDY_SECTION_NAME: Clinical Aging Study Section[NIA-C]


NIH_SPENDING_CATS: Aging;Atherosclerosis;Behavioral and Social Science;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Prevention;Social Determinants of Health

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: PROJECT NARRATIVE Cardiovascular disease (CVD) is a leading cause of disability and death among U.S. older adults and represents an enormous public health burden. Although CVD risk assessment is recommended as the foundation to primary prevention and guiding treatment decisions, the current tool for risk assessment performs poorly in older adults and among disadvantaged population groups. We propose to address these limitations by incorporating changes in risk factors over time and integrating social determinants of health to improve CVD risk-prediction and its translation to disease prevention in U.S. older adults.

PI_NAMEs: DUPRE, MATTHEW E. (contact)

PROGRAM_OFFICER_NAME: BANDIERA, FRANK

PROJECT_TERMS: Accounting;Address;Adopted;Adult;Age;age related;age related changes;age related decline;Aging;American;American Heart Association;Atherosclerosis Risk in Communities;Behavioral;Blood Pressure;Blood Vessels;Cardiology;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Caring;Cessation of life;Cholesterol;Classification;Clinical;cohort;college;Communication;Communities;Data;design;Development;disability;Disease;Disease Outcome;disorder prevention;disorder risk;Disparity population;Education;Elderly;Event;evidence base;Exercise;follow-up;Foundations;Goals;Guidelines;Hazard Models;Health;Health and Retirement Study;human old age (65+);implementation study;improved;Individual;innovation;Intervention;Knowledge;Measures;Medical;Mental Depression;Methods;Mission;Modeling;Multi-Ethnic Study of Atherosclerosis;multiple datasets;offspring;older adult;Onset of illness;Patients;Performance;Persons;Physiological;Population;Population Group;Population Heterogeneity;predictive modeling;prevent;Preventive therapy;Primary Prevention;prospective;psychosocial;Public Health;Recommendation;Risk;Risk Assessment;Risk Factors;risk prediction;Risk Reduction;routine care;Sampling;Series;shared decision making;social determinants;social health determinants;Social support;socioeconomics;support tools;Time;tool;Translating;Translations;treatment strategy;United States;United States National Institutes of Health;Validation;Visualization

PROJECT_TITLE: Integrating Risk Trajectories and Social Determinants to Enhance Cardiovascular Risk Assessment in Older Adults

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


ORG_CITY: SHREVEPORT

ORG_NAME: LOUISIANA STATE UNIV HSC SHREVEPORT

ORG_STATE: LA

PHR: PROJECT NARRATIVE Functional alterations in the endothelial cells lining the vessel wall represent an important step in atherosclerotic initiation, progression, and clinical complications. Our research identifies Nck1 and IRAK1 as novel players in this process, regulating proinflammatory gene expression in response to changes in the local microenvironment. Understanding the molecular mechanisms controlling endothelial cell function by the microenvironment may provide novel therapeutic targets to limit chronic inflammatory diseases, such as atherosclerosis and arthritis.

PI_NAMEs: ORR, ANTHONY WAYNE (contact)

PROGRAM_OFFICER_NAME: PLAYFORD, MARTIN P

PROJECT_TERMS: Adaptor Signaling Protein;Affect;angiogenesis;antagonist;Arterial Fatty Streak;Arthritis;Atherosclerosis;Blood Vessels;Bone Marrow;Cardiovascular Diseases;Cell Adhesion Molecules;Cell Culture Techniques;Cell Line;cell motility;Cell Physiology;Cell-Matrix Junction;Cells;Chimera organism;chronic inflammatory disease;Clinical;Complex;Coronary Arteriosclerosis;cytokine;Cytoskeleton;Defect;Development;Endothelial Cells;Endothelium;experimental study;Family;Funding;Gene Expression;genome wide association study;Growth Factor Receptors;hemodynamics;human disease;IL1R1 gene;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Interleukin-1;Interleukin-1 Receptors;IRAK1 gene;Ischemia;ischemic injury;Knock-out;Knockout Mice;Laboratories;leukocyte homing;Leukocytes;Ligands;Ligation;Link;Lipids;Macrophage;Mediating;Molecular;Mus;Mutation Analysis;new therapeutic target;novel;Nuclear;Pattern;Permeability;pharmacologic;Phospholipids;Play;Point Mutation;prevent;Process;Protein Isoforms;receptor;recruit;Regulation;Research;response;Retinal Neovascularization;Role;SH3 Domains;shear stress;Signal Transduction;Site;Smooth Muscle;src Homology Region 2 Domain;Therapeutic;therapeutic target;Transactivation;Tyrosine Phosphorylation Site;Vascular remodeling

PROJECT_TITLE: Nck adaptor proteins in atherogenic endothelial activation

STUDY_SECTION: AICS

STUDY_SECTION_NAME: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Social Determinants of Health;Women's Health Research

ORG_DEPT: GENETICS

PHR: Project Narrative Our proposed work will test the role of SEMA6D-mediating tumor metastasis and racial disparities in breast cancer. Our results will move beyond an incremental advancement and accelerate the development of new therapeutics to improve clinical outcomes in African American patients with breast cancer.

PI_NAMEs: JIAO, KAI ;WANG, LIZHONG  (contact)

PROGRAM_OFFICER_NAME: GRIL, BRUNILDE M

PROJECT_TERMS: Acceleration;Affect;African American;African American Women;American;Bioinformatics;Biological;Biological Factors;Biological Markers;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Patient;breast cancer survival;cancer cell;cancer diagnosis;Cancer Etiology;cancer health disparity;cancer type;caucasian American;Cell Culture Techniques;Cells;Cessation of life;Clinical;clinical application;CXCL2 gene;Data Set;Death Rate;Development;Diagnosis;differential expression;Disparity;DNA Methylation;early onset;Epigenetic Process;ERBB2 gene;Family;Foundations;Genes;Goals;Human;Immune;improved;in vivo;Invaded;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Gland Parenchyma;Mediating;member;Metastatic Neoplasm to Lymph Nodes;Methylation;migration;Mouse Mammary Tumor Virus;mouse model;Multivariate Analysis;Mus;Neoplasm Metastasis;neoplastic cell;Non-Malignant;Normal tissue morphology;novel;novel diagnostics;novel therapeutics;Outcome;outcome disparities;overexpression;Pathogenesis;patient derived xenograft model;Patients;Prognosis;promoter;Promoter Regions;Protein Analysis;protein expression;Protein Isoforms;Proteins;Race;racial disparity;Reagent;receptor;Reporting;Research;Role;Sampling;Semaphorins;Signal Transduction;Signaling Molecule;single-cell RNA sequencing;Socioeconomic Factors;Specimen;Technology;Testing;Therapeutic;Time;Tissues;tool;Transcript;Transgenic Mice;triple-negative invasive breast carcinoma;tumor;tumor microenvironment;Tumor stage;Woman;Women's mortality;Work;Xenograft procedure

PROJECT_TITLE: SEMA6D-mediated breast cancer disparity, metastasis, and tumor-immune interaction

STUDY_SECTION: BMCD

STUDY_SECTION_NAME: Basic Mechanisms of Cancer Health Disparities Study Section[BMCD]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Physical Activity

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: PROJECT NARRATIVE Many people suffer from Heart Failure with Preserved Ejection Fraction (HFpEF), but unfortunately, we do not have any drug treatments that consistently improve the disability and reduced quality of life caused by this syndrome. The goal of this proposal is to test whether new drugs and drug combinations can increase exercise tolerance in HFpEF patients by improving how the skeletal muscle gets blood and generates energy. We hope that this proposal will identify new ways to treat HFpEF patients, allowing these individuals, who are currently very limited in what they can do and how they feel, to enjoy life more.

PI_NAMEs: ZAMANI, PAYMAN  (contact)

PROGRAM_OFFICER_NAME: TINSLEY, EMILY

PROJECT_TERMS: Acceleration;Acetylcarnitine;active control;Address;Aerobic;Biochemical;Biopsy Specimen;Blood;Clinical Trials;Combined Modality Therapy;Complex;Cross-Over Trials;Data;diagnostic strategy;disability;Double-Blind Method;Drug Combinations;EFRAC;endurance exercise;Exercise;exercise capacity;Exercise Tolerance;Exertion;Goals;Heart failure;Heterogeneity;impaired capacity;Impairment;improved;Individual;individual response;insight;Intervention;Intramuscular;Kinetics;Left;Levocarnitine;Life;Magnetic Resonance Imaging;Measurement;Measures;Metabolic;Mitochondria;Movement;Muscle;nicotinamide-beta-riboside;Nitrates;novel;novel diagnostics;novel therapeutics;Oxidative Phosphorylation;Oxygen;Patients;Perfusion;Persons;pharmacologic;Pharmacotherapy;Phenotype;Potassium Chloride;potassium nitrate;preservation;prevent;primary endpoint;Process;Production;propionyl-coenzyme A;Quality of life;Randomized;response;secondary endpoint;Skeletal Muscle;success;supplemental oxygen;Syndrome;Techniques;Testing;Therapeutic;Therapeutic Intervention;Time;Translating;treatment response;uptake;Work

PROJECT_TITLE: Targeting Skeletal Muscle Perfusion and Oxidative Capacity in HFpEF

STUDY_SECTION: CICS

STUDY_SECTION_NAME: Clinical and Integrative Cardiovascular Sciences Study Section[CICS]


ADMINISTERING_IC: GM

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: MADISON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Ion channels and transporters regulate the movement of ions and small molecules across biological membranes. We use NMR spectroscopy together with biochemical and functional assays to decipher the molecular mechanism of these integral membrane proteins. We use this knowledge both to gain insight into fundamental biological processes and to assess how we might target bacterial transporters to develop new antibiotics.

PI_NAMEs: HENZLER-WILDMAN, KATHERINE ANNE (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Active Biological Transport;Address;Allosteric Regulation;Antibiotics;Binding;Biochemical;Biological;Biological Assay;Biological Models;Biological Process;Biophysics;Chemicals;Coupled;Data;Environment;In Vitro;in vivo;insight;Integral Membrane Protein;Ion Channel;Ions;Kinetics;Knowledge;Length;Membrane;Membrane Proteins;Modeling;Molecular;Molecular Probes;Monitor;Motion;Movement;NMR Spectroscopy;Pharmaceutical Preparations;Population;Process;Protein Conformation;protein function;Proteins;Protons;Pump;Research;Resolution;Site;small molecule;Specificity;Structure;System;Temperature Sense;Thermodynamics;Time;tool;Work

PROJECT_TITLE: Molecular Mechanisms of Channels and Transporters

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


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

ORG_CITY: ANN ARBOR

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Millions of patients suffer from life-threatening accidents and sudden medical emergencies every year, and the technologies used to diagnose, monitor, and treat these patients have special engineering requirements compared to technologies for any other health condition. Given the abruptness and urgency of acute illnesses and injuries, technologies must work very rapidly, be highly accurate, and be easy to use by various medical personnel both in and outside the hospital (e.g., in ambulances), yet students are rarely taught how to address these unique design issues. The new Acute and Critical Care Engineering (ACCE) Training Program will provide Engineering pre-doctoral students with interdisciplinary mentorship, specialized curriculum tracks, clinical immersion, focused design training, and entrepreneurial workshops, equipping them to address these engineering challenges and collaboratively develop, test, and commercialize new life-saving technologies.

PI_NAMEs: DANIELS, RODNEY C;OLDHAM, KENN R (contact);WARD, KEVIN

PROGRAM_OFFICER_NAME: GUTEKUNST, DAVID JOSEPH

PROJECT_TERMS: acute care;Critical Care;Engineering;Training Programs


ADMINISTERING_IC: LM

IC_NAME: NATIONAL LIBRARY OF MEDICINE

NIH_SPENDING_CATS: Breast Cancer;Cancer;Data Science;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Precision Medicine;Women's Health Research

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Narrative In order to discover and generate new pharmacogenetic hypotheses from drug interaction evidences published in the scientific literature, we will develop novel machine learning methods, including active learning allowing human involvement and knowledge base reasoning. These new pharmacogenetics hypotheses will be tested in a biobank. These pharmacogenetics findings will contribute significantly towards precision medicine and improve clinical care.

PI_NAMEs: CHEN, YOU ;LI, LANG  (contact);SU, YU

PROGRAM_OFFICER_NAME: DENNIS, ALLISON FRANCES

PROJECT_TERMS: Active Learning;Adverse drug event;Adverse event;Alleles;anti-depressive agents;Applications Grants;artificial intelligence method;base;Big Data;biobank;Breast Cancer therapy;Clinical;clinical care;Communities;Computerized Medical Record;CYP2C19 gene;CYP2D6 gene;CYP3A4 gene;Data;design;Development;Disease-Free Survival;Drug Interactions;Drug Kinetics;drug metabolism;Enzyme Induction;Enzyme Inhibition;Enzymes;feasibility research;Feedback;Generations;Genes;Genetic Polymorphism;genetic variant;hormone therapy;Human;improved;Information Retrieval;inhibitor;innovation;interest;Investigation;Joints;Knowledge;knowledge base;Knowledge Discovery;knowledgebase;Literature;loss of function;Machine Learning;machine learning algorithm;machine learning method;Malignant Breast Neoplasm;Metabolism;Methodology;Methods;Myopathy;Natural Language Processing;Nested Case-Control Study;novel;Omeprazole;Paper;Patients;Performance;Pharmaceutical Preparations;pharmacogenetic testing;Pharmacogenetics;pharmacologic;precision medicine;Prospective Studies;Publishing;PubMed;Research;Resources;Retrieval;Sampling;Scheme;Selective Serotonin Reuptake Inhibitor;Tamoxifen;Testing;Time;Translational Research;Translations;Transportation;tumor;Universities;Variant;Work

PROJECT_TITLE: Machine learning drives translational research from drug interactions to pharmacogenetics

STUDY_SECTION: BDMA

STUDY_SECTION_NAME: Biodata Management and Analysis Study Section[BDMA]


NIH_SPENDING_CATS: Drug Abuse (NIDA only);Substance Misuse

ORG_CITY: CHARLESTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE The effectiveness of treating substance use disorders is based on our understanding of drug addiction and the currently available intervention approaches. The proposed training program addresses this need by providing young basic and clinical scientists with the knowledge base and the research skills to investigate the neurobiology of substance use disorders and develop therapeutic strategies to treat addiction.

PI_NAMEs: MCGINTY, JACQUELINE F. (contact)

PROGRAM_OFFICER_NAME: FALCON-MORALES, EDGARDO

PROJECT_TERMS: Drug abuse;Training Programs

PROJECT_TITLE: Drug Abuse Training Program


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: HOUSTON

ORG_DEPT: PEDIATRICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Since its discovery, adult mammalian hippocampal neurogenesis—particularly human—has attracted attention and controversy, as examining it directly has been hindered by the lack of an in vivo measure that can be performed in the human (post mortem studies using immunostaining are quite limiting). Our group has identified the first and only in vivo, non-invasive, magnetic resonance spectroscopy (MRS)-based biomarker of neurogenesis: a lipid-based signal resonating at 1.28ppm. Here, we propose to develop data acquisition and processing techniques to significantly enhance biomarker detection and quantification in vivo so that it might become a widely-adopted measure of adult human neurogenesis that will inform a wide range of studies on memory, aging, AD/ADRD, depression, and a range of other conditions.

PI_NAMEs: MALETIC-SAVATIC, MIRJANA  (contact);STARK, CRAIG E

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: Address;Adolescent;Adopted;Adult;adult neurogenesis;Age;age effect;age related decline;aged;Aging;Agreement;Alzheimer's Disease;Alzheimer's disease related dementia;analytical method;Animal Model;Area;Attention;Autopsy;Behavioral;Biological Markers;biomarker validation;Brain;Bromodeoxyuridine;Cells;Clinical;computerized data processing;convolutional neural network;Data;data acquisition;deep learning;Detection;detection method;Disease;Drops;Electroconvulsive Therapy;environmental enrichment for laboratory animals;Excision;Foundations;gamma-Aminobutyric Acid;Goals;Hippocampus;Human;Image;Impairment;improved;In Vitro;in vivo;in vivo magnetic resonance spectroscopy;innovation;interest;Learning;Ligands;Lipids;Machine Learning;Magnetic Resonance Spectroscopy;Major Depressive Disorder;Measurement;Measures;Memory;Mental Depression;Methods;model organism;Modeling;Monounsaturated Fatty Acids;Moods;Mus;Natural regeneration;nerve stem cell;Network-based;neural;neural network;neurogenesis;newborn neuron;Newly Diagnosed;Noise;novel;novel strategies;Nuclear Receptors;Oleic Acids;Pathway Analysis;Pattern Recognition;Performance;Pharmaceutical Preparations;Process;Proliferating;Protocols documentation;repaired;Reproducibility;Resistance;response;Rodent;Scanning;Sensitivity and Specificity;Signal Transduction;Site;Specificity;Spectrometry;Statistical Data Interpretation;stem;stem cell self renewal;stem cells;Techniques;Time;Tissues;tool;Validation;Wild Type Mouse;Work

PROJECT_TITLE: Using MR Spectroscopy to Measure Mammalian Neurogenesis in Vivo


ADMINISTERING_IC: DK

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Aging;Clinical Research;Clinical Trials and Supportive Activities;Dietary Supplements;Digestive Diseases;Estrogen;Microbiome;Nutrition;Prevention;Women's Health Research

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Fecal incontinence (FI) is a common, yet debilitating gastrointestinal disorder impacting 1 in 10 people and associated with significant healthcare costs. In this proposal, we will comprehensively investigate the role of both dietary and supplemental fiber in relation to risk and progression of FI and examine the interplay between fiber, symptoms, hormones, and the gut microbiome. Our study has the potential to lead to clinical recommendations regarding the use of dietary fiber among people at-risk for FI or with established FI and will offer new insights into FI etiopathogenesis.

PI_NAMEs: STALLER, KYLE  (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: Adult;Affect;Aging;Atmosphere;Award;Bacteria;Beta-glucuronidase;Bioinformatics;Biological;Blood specimen;Butyrates;career;career development;Clinical;Clinical Investigator;Clinical Research;Clinical Trials;Clinical Trials Design;cohort;Complex;Data;Data Set;design;Development;Dextrins;Diarrhea;Diet;Diet Modification;dietary;Dietary Factors;Dietary Fiber;Dietary intake;Disease;Economic Burden;Elderly woman;Ensure;Environment;Epidemiologic Methods;Epidemiologist;Epidemiology;Esthesia;Estradiol;Estrogen Metabolism;Estrogens;Estrone;Estrone-Sulfate;Etiology;Fecal Incontinence;Feces;Fermentation;Fiber;Firmicutes;Frequencies;Funding;Gastrointestinal Diseases;Genetic;Genetic Predisposition to Disease;genome wide association study;Germ Lines;Goals;gut metagenome;gut microbiome;gut microbiota;Health Care Costs;Hormones;Human;improved;innovation;insight;Institution;Intake;Intestines;Irritable Bowel Syndrome;Knowledge;Laboratories;Life Style;lifestyle data;Liquid substance;Longitudinal cohort;Manometry;Measurement;Measures;Mediating;menopausal hormone therapy;Mentors;Mentorship;metabolome;metabolomics;metagenome;Metagenomics;Methodology;microbial;microbiome;microbiome alteration;microbiota;Motility;Motor;multidisciplinary;multimodal modeling;Nurses' Health Study;nutritional epidemiology;open label;Patients;Persons;Physicians;Physiological;Physiology;Population;population based;Populations at Risk;Postmenopause;Prevalence;Prevention;Prevention strategy;Production;programs;Prospective cohort;Public Health Schools;Publications;Quality of life;Recommendation;Research;Research Personnel;Risk;Risk Factors;Role;Sensory;Series;Serum;Severities;skill acquisition;skills;Solubility;soluble fiber;stool sample;success;Supervision;Supplementation;Susceptibility Gene;Symptoms;Target Populations;Training;Translational Research;Wheat;Woman;Work

PROJECT_TITLE: The Role of Fiber in the Etiopathogenesis of Fecal Incontinence

STUDY_SECTION: DDK

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


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: BLACKSBURG

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

ORG_STATE: VA

PHR: PROJECT NARATIVE Mitophagy removes damaged mitochondria inside the cell and the accumulation of dysfunctional mitochondria impacts the ability for the cell to make energy. Our proposed studies will reveal how mitophagy impacts and influences other cellular processes such as cell division and inflammation in different cell types. The information gained will inform us on how mutations in mitophagy genes contribute to a complex, diverse array of diseases such as cancer, encephalitis, and neurodegenerative disorders.

PI_NAMEs: PICKRELL, ALICIA M (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Affect;autosome;Biochemical;Cell division;Cell Physiology;cell type;Cells;Cellular biology;Centrosome;Cognition Disorders;Complex;daughter cell;Defect;Disease;Drosophila genus;Encephalitis;Ensure;Genes;Genetic;Goals;human disease;Image;Inflammation;insight;life span;Link;Malignant Neoplasms;Mitochondria;mitochondrial dysfunction;Mitochondrial Inheritance;mouse model;Mutate;Mutation;Neurodegenerative Disorders;Neurodevelopmental Disorder;Organelles;Oxidative Phosphorylation;Parkinson Disease;Phosphotransferases;postmitotic;prevent;Process;Proteins;Quality Control;Recycling;response;Signal Transduction;stem cell division;stem cells;Transgenic Mice;Work

PROJECT_TITLE: Global Intracellular Responses to Mitophagy

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


NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Data Science;Digestive Diseases;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pancreatic Cancer;Patient Safety;Prevention;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: The goal of this proposal is to develop new protocols for the early detection of pancreatic cancer, using a novel strategy for combining human-expert knowledge with deep neural networks. Our study will systematically derive feature grouping strategies from clinical workflows using Electronic Health Records (EHR) to develop predictive and potentially insightful deep learning models. As a result, we will be able to propose new predictors associated with pancreatic cancer represented by single or composite variables according to the grouping strategies and their causal relationships.

PI_NAMEs: PARK, JIHEUM  (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Address;Adoption;Algorithms;Architecture;Artificial Intelligence;artificial neural network;Bayesian Network;Black Box;Breast;Cancer Detection;Cancer Etiology;cancer type;Categories;Cessation of life;Clinical;clinical practice;clinical predictors;Collection;Colorectal;Data;Data Collection;Data Set;deep learning;deep learning algorithm;deep learning model;deep neural network;Development;Diagnosis;Early Diagnosis;Electronic Health Record;Future;Generations;generative models;Genetic Risk;Goals;Grouping;Health Benefit;health data;Healthcare;high risk;Human;human-in-the-loop;improved;Individual;innovation;Institution;Intervention;Knowledge;Laboratories;Learning;Literature;Logistic Regressions;Lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Medical;Medical center;Medical Records;Methodology;Methods;Modeling;Modernization;Morbidity - disease rate;mortality;multimodal data;multimodality;neural network architecture;neurodevelopment;novel;novel strategies;Obesity;Output;pancreas imaging;Pancreatic Ductal Adenocarcinoma;Pathway interactions;patient variability;Patients;Performance;Pharmaceutical Preparations;Population;predictive modeling;prevent;Procedures;Process;Prostate;Protocols documentation;Public Health;Questionnaires;Reporting;Research;Risk;Risk Assessment;Risk Factors;risk prediction;screening;Series;Signal Transduction;Signs and Symptoms;Structure;Surveys;System;Taxonomy;Techniques;Text;Time;Tobacco use;Training;trend;Universities;Visualization

PROJECT_TITLE: Early Detection of Pancreatic Cancer with Human-in-the-Loop Deep Learning

STUDY_SECTION: NCI

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


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE Although metabolic demand from neuronal function has been shown to regulate angiogenesis in the retina, a thorough mechanistic understanding of how neuronal activity regulates retinal angiogenesis and blood-retinal barrier maturation remains unknown. Using genetic models to modulate cholinergic and glutamatergic neuronal activities, this project will explore how these two types of neuronal activities (separately or in combination) regulate retinal angiogenesis and blood-retinal barrier maturation. The knowledge gathered from this project may be of critical importance to develop novel therapeutic interventions for degenerative diseases and ischemic retinopathies of the eye.

PI_NAMEs: BISWAS, SAPTARSHI  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Address;Affect;angiogenesis;Astrocytes;Basement membrane;beta catenin;Blood Vessels;Blood-Retinal Barrier;Caveolae;Cell Count;Cell Death;Cell Proliferation;Cells;cholinergic;cholinergic neuron;Data;Defect;Degenerative Disorder;Development;early onset;Endothelial Cells;Endothelium;Enzymes;excitotoxicity;extracellular;Eye;genetic approach;Genetic Models;GLAST Protein;Glutamate Receptor;Glutamate Transporter;Glutamate-Ammonia Ligase;glutamatergic signaling;Glutamates;Glutamine;Growth;Impairment;insight;Ischemia;Knowledge;Ligands;Measures;Mediating;Membrane Proteins;Metabolic;Mouse Strains;Muller's cell;Mus;Mutant Strains Mice;Nerve Degeneration;neural;Neurodegenerative Disorders;Neuroglia;Neurons;Neurotransmitters;neurovascular unit;notch protein;novel;novel therapeutic intervention;Pathway interactions;PECAM1 gene;Permeability;pharmacologic;Phase;Phenotype;photoactivation;Photoreceptors;postnatal;Process;response;Retina;retinal angiogenesis;Retinal Diseases;Retinal Ganglion Cells;retinal rods;Role;sensor;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Synapses;Testing;Tight Junctions;Tracer;Transcript;transcriptomics;Transducers;Transforming Growth Factor beta;uptake;Vascular Endothelial Growth Factors;vascular factor

PROJECT_TITLE: The role of neuronal activity on retinal angiogenesis and blood-retina barrier (BRB) maturation


NIH_SPENDING_CATS: Bioengineering;Cancer;Immunotherapy;Networking and Information Technology R&D (NITRD);Precision Medicine;Urologic Diseases

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: Project Narrative We propose to combine novel cellular quantification experimental technologies with multiscale mathematical approaches in order to gain a deeper, more robust understanding of tumor-immune dynamics and to harness this knowledge for human benefit. Using bladder cancer as our platform, we will develop a comprehensive and predictive 3D computational framework that will be used to optimize combination immunotherapy and receptor kinase targeted therapy. Our experimentally- driven multiscale approach is poised to significantly enhance the current understanding of differential cell-kill mechanisms on tumor-immune outcomes and to improve the ability to combine promising drugs for clinical trials.

PI_NAMEs: JACKSON, TRACHETTE  (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: 3-Dimensional;Address;Affect;alternative treatment;American;Antigens;Basic Science;Behavior;Biological;Biological Assay;Biological Models;Bladder Neoplasm;Calibration;cancer cell;Cancer Model;Cancer Patient;cancer therapy;Cause of Death;CD8-Positive T-Lymphocytes;cell behavior;Cell Communication;cell growth;cell killing;cell motility;Cells;Cessation of life;checkpoint inhibition;checkpoint therapy;chemotherapy;Clinical;Clinical Research;Clinical Trials;clinically relevant;Combination immunotherapy;Combined Modality Therapy;Computational Biology;computational platform;computer framework;Computer Models;Cytoplasmic Granules;cytotoxicity;Data;design;Diagnosis;Drug Targeting;Evaluation;experimental study;FDA approved;FGFR3 gene;Fibroblast Growth Factor Receptors;Future;Goals;Human;Hybrids;Image;Immune;immune checkpoint;Immune checkpoint inhibitor;Immune system;Immunohistochemistry;Immunotherapy;improved;in silico;Individual;information gathering;inhibitor;inhibitor therapy;innovation;insight;kinase inhibitor;Knowledge;Laboratories;Ligands;live cell imaging;Malignant neoplasm of urinary bladder;Malignant Neoplasms;mathematical methods;mathematical model;Mathematics;Measures;Mediating;Modeling;Molecular;Molecular Target;Monoclonal Antibodies;movie;multi-scale modeling;Mutation;neoplastic cell;Nivolumab;novel;novel drug combination;objective response rate;Outcome;Pathway interactions;Patient-Focused Outcomes;Persons;Pharmaceutical Preparations;Phenotype;Phosphotransferases;Prediction of Response to Therapy;programmed cell death ligand 1;Proteins;Publishing;receptor;Receptor Protein-Tyrosine Kinases;Resistance;response;Schedule;small molecule;small molecule inhibitor;spatiotemporal;Speed;Survival Rate;synergism;T-Lymphocyte;targeted agent;targeted treatment;Technology;Testing;Theoretical Studies;Therapeutic;therapeutic effectiveness;therapy design;therapy development;Time;tool;Translating;Treatment Failure;treatment optimization;Treatment Protocols;treatment response;treatment strategy;tumor;tumor growth;Tumor Necrosis Factor Ligand Superfamily Member 6;Tyrosine Kinase Inhibitor;United States;Urinary system;Work

PROJECT_TITLE: Multiscale Computational Models Guided By Emerging Cellular Dynamics Quantification For Predicting Optimum Immune Checkpoint And Targeted Therapy Schedules


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Autoimmune Disease;Clinical Research;Precision Medicine;Prevention;Rheumatoid Arthritis

ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Individuals who have developed rheumatoid arthritis (RA) demonstrate several unique types of inflammatory and autoimmune cell patterns in the inflamed synovium. Molecular dissection of the synovial tissue in patients with RA has identified a number of new features with pathogenic, personalized therapeutic and prognostic importance. Using a pipeline of synovial samples obtained from patients with RA, this group will advance the field by increasing our understanding of the three-dimensional architecture and mechanisms by which cell populations interact both with each other and the systemic immune system, as well as interlink these phenotypes to patient characteristics and response to specific therapy.

PI_NAMEs: ANOLIK, JENNIFER HOWITT (contact);DONLIN, LAURA T.;MORELAND, LARRY W

PROGRAM_OFFICER_NAME: WANG, YAN Z

PROJECT_TERMS: 3-Dimensional;Address;adverse outcome;Affect;Algorithms;Architecture;Area;Arthritis;Artificial Intelligence;Autoantibodies;Autoimmune;B-Lymphocytes;Binding;biobank;Biological;Biological Markers;Biological Response Modifier Therapy;Biopsy;bone cell;Cell Communication;Cells;Characteristics;Classification;Clinical;clinical phenotype;Clinical Research;Clinical Trials;cohort;Complement;Data;design;Diagnosis;disability;Disease;Disease Outcome;Disease remission;Disease-Modifying Second-Line Drugs;disorder prevention;Dissection;Dissociation;Drug Targeting;Early treatment;effector T cell;Enrollment;Ensure;Environmental Exposure;epigenetic regulation;Evolution;Failure;Fibroblasts;Flare;follow-up;Funding;Generations;Goals;Heterogeneity;high dimensionality;Histology;Image;Immune;Immune system;improved;In Situ;Individual;individualized medicine;Inflammation;Inflammatory;innovation;joint inflammation;joint injury;Knowledge;Longitudinal Studies;Measurement;Mediator;Methotrexate;Molecular;Molecular Analysis;monocyte;multimodal data;multimodality;novel;Onset of illness;Oranges;Outcome;Pain;Pathogenesis;Pathogenicity;Pathologic Processes;Pathway interactions;Patient Care;Patient Recruitments;patient retention;Patients;Pattern;personalized therapeutic;Phenotype;phenotypic data;Population;Positioning Attribute;pre-clinical;Precision therapeutics;Preparation;prevent;Prevention strategy;Process;prognostic;programs;Protocols documentation;Psoriatic Arthritis;reconstruction;Research Personnel;response;Rheumatoid Arthritis;Risk;Role;Sampling;Science;Selection for Treatments;Seminal;Site;small molecule;Specimen;standard of care;Synovial Cell;Synovial Fluid;Synovial Membrane;Synovitis;Systemic Lupus Erythematosus;Technology;tissue reconstruction;Tissue Sample;Tissues;transcriptomics;translational applications;Treatment Failure;Treatment outcome;treatment response;treatment strategy;United States National Institutes of Health;Variant

PROJECT_TITLE: AIM-for-RA


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Orphan Drug;Precision Medicine;Rare Diseases

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: Project narrative Glioblastoma (GBM) has a grim prognosis with median survival of approximately 14-16 months which hasn't changed in over 15 years. Machine learning has offered great promise in a number of areas in which complex information is to be synthesized for decision making. The current project proposes to refine quantitative imaging methods leveraging machine learning (QIML), with emphasis on a) obtaining rich imaging phenotypes relying on multi-parametric signals, textures, shape properties, spatial patterns derived from atlas registration, and biophysical models of tumor growth, and b) integrating such imaging signatures using machine learning into predictors of clinical outcome, as well as of early recurrence from peri-tumoral infiltration. A unique consortium of 14 leading institutions internationally and over 4,500 patients/MRIs will be leveraged for training and testing these QIMLs. This unique software and data resource will likely further mobilize a broad community of quantitative imaging researchers of GB around the world and provide precision diagnostics and personalized AI-guided treatments.

PI_NAMEs: DAVATZIKOS, CHRISTOS  (contact)

PROGRAM_OFFICER_NAME: ZHANG, HUIMING

PROJECT_TERMS: Area;Astrocytoma;Atlases;biophysical model;Brain Neoplasms;cancer imaging;Characteristics;Clinical;clinical practice;clinical trial enrollment;Clinical Trials;Communities;Complex;Computer software;Data;data resource;Data Set;Databases;Decision Making;deep learning;Diffusion;disease heterogeneity;Excision;Foundations;Genomics;Glioblastoma;Glioma;Goals;Guidelines;Heterogeneity;heterogenous data;Image;Image Analysis;imaging modality;improved;improved outcome;in vivo evaluation;Infiltration;Institution;International;Laboratories;Life;Machine Learning;machine learning method;machine learning model;machine learning prediction;Magnetic Resonance Imaging;Malignant neoplasm of brain;Malignant Neoplasms;Measures;Metabolic;Methods;Methylation;MGMT gene;Molecular;mutant;neuro-oncology;open source;Outcome;Patients;Pattern;Perfusion;personalized diagnostics;personalized medicine;personalized predictions;Phase;phase II trial;phenomics;Phenotype;Physiological;predict clinical outcome;predictive modeling;Prognosis;programs;Progression-Free Survivals;Progressive Disease;promoter;Property;Protocols documentation;quantitative imaging;Radiation;Radiology Specialty;radiomics;Recurrence;Recurrent tumor;Reproducibility;Research;Research Personnel;Scanning;Shapes;Signal Transduction;Site;Stratification;Testing;Texture;Tissues;tool;Training;treatment effect;treatment planning;treatment strategy;treatment stratification;treatment trial;tumor;tumor growth;Update

PROJECT_TITLE: Generalizable quantitative imaging and machine learning signatures in glioblastoma, for precision diagnostics and personalized treatment: the ReSPOND consortium

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: AA

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Biotechnology;Brain Disorders;Neurosciences;Substance Misuse

ORG_CITY: SAN DIEGO

ORG_NAME: STRESS THERAPEUTICS, INC.

PHR: Narrative. Stress is commonly experienced in daily life. However, excessive activation of the stress system can result in reduced resilience and predisposes to alcohol and drug abuse as well as a variety of illnesses. This Phase II SBIR proposal seeks to develop a novel therapeutic to reduce the detrimental consequences of hyperactivity of the hypothalamic pituitary adrenal axis (HPA), which characterizes alcohol use disorder (AUD) as well as other conditions including drug abuse, depression, Alzheimer’s and Parkinson’s diseases, among others.

PI_NAMEs: LLOYD, LINDA S (contact)

PROGRAM_OFFICER_NAME: EGLI, MARK

PROJECT_TERMS: Adrenal Glands;Affinity;Alcohol abuse;alcohol use disorder;Alzheimer's Disease;antagonist;Antibodies;Area;Automobile Driving;behavior measurement;Binding;Biological;biological adaptation to stress;Biological Products;Biological Response Modifier Therapy;Biological Sciences;Bioreactors;cell bank;Cell Line;Cells;Chimeric Proteins;Chinese Hamster Ovary Cell;Chronic;Circulation;Clinical;clinical development;Clinical Trials;Cloning;Codon Nucleotides;Core Facility;Corticosterone;Corticotropin;corticotropin releasing factor-binding protein;Corticotropin-Releasing Hormone;Corticotropin-Releasing Hormone Receptors;design;Development;Dissociation;Dose;Drug abuse;Drug Kinetics;Electroporation;Endotoxins;Ensure;Evaluation;experience;Experimental Designs;Fc Receptor;Feedback;first-in-human;flasks;flexibility;Foundations;gene cloning;gene synthesis;Generations;Glucocorticoid Receptor;Glucocorticoids;good laboratory practice;Half-Life;Hormones;Human;Hydrocortisone;Hyperactivity;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;IgG2;Immunoglobulin G;Immunology;Investigational Drugs;Kinetics;Lead;Length;Letters;Life;Mediating;Medical;Mental Depression;Mineralocorticoid Receptor;Mus;Mutation;neonatal Fc receptor;Neuropharmacology;Neurosciences;Neurosecretory Systems;novel;novel therapeutics;Outcome;Parkinson Disease;Pathogenesis;Pathologic;Pathway interactions;Peripheral;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Pharmacology;Phase;Pituitary Gland;Plasma;Printing;Production;professor;Property;receptor;Receptor Activation;Recycling;Research;Research Contracts;Research Institute;resilience;response;Risk;Safety;Small Business Innovation Research Grant;stable cell line;Stress;System;Testing;Therapeutic;therapeutic target;Time;Toxicology;Work

PROJECT_TITLE: Novel therapeutic for HPA hyperactivity


ADMINISTERING_IC: HG

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROGRAM NARRATIVE The overall goal of this post-doctoral training program in genomic medicine is to provide clinical/translational scientists with a multiyear training program comprised of didactic, research, clinical genomic medicine, and leadership training. At the end of their training period, trainees possess knowledge and skills that will enable them to manage the challenges of evidence generation and clinical use of genomic medicine.

PI_NAMEs: DUARTE, JULIO DAVID (contact);KIMMEL, STEPHEN E.

PROGRAM_OFFICER_NAME: COLLEY, HEATHER

PROJECT_TERMS: Applied Research;Genomic medicine;research and development;Training Programs

PROJECT_TITLE: Training Program for Applied Research and Development in Genomic Medicine


NIH_SPENDING_CATS: Biotechnology;Complementary and Integrative Health;Natural Products

ORG_CITY: ALBUQUERQUE

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF NEW MEXICO

ORG_STATE: NM

PHR: Project narrative  Chemicals produced by living organisms, or natural products, serve as the basis for a large number of pharmaceuticals on the market today. As genome sequencing has become more accessible, it has become apparent that the number of natural products that have been characterized is dwarfed by the number of biological pathways that exist in nature that can produce them, suggesting there are many more compounds to be discovered. To efficiently explore the compounds that could be produced by some of these pathways we are studying the enzymes that biosynthesize a class of natural products, and through these studies will develop an approach to produce millions of natural product-like compounds and test them for biological activity useful for the treatment of disease.

PI_NAMEs: WALKER, MARK CHALFANT (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Acceleration;Anabolism;Antibiotics;Antineoplastic Agents;Biological;Chemicals;Diagnosis;Disease;Dwarfism;enzyme biosynthesis;enzyme substrate;Enzymes;Fluorescence-Activated Cell Sorting;Focus Groups;Gene Library;genome sequencing;Health;Human;Libraries;Marketing;Mutation Analysis;natural product derivative;Natural product discovery;natural product inspired;Natural Products;Nature;next generation sequencing;novel strategies;Organism;Pathway interactions;peptide natural products;Peptides;Pharmaceutical Preparations;Pharmacologic Substance;Ribosomes;small molecule;Surface;Testing;tool;Variant;Yeasts

PROJECT_TITLE: High throughput biosynthesis of ribosomally synthesized and post-translationally modified peptide natural products

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


NIH_SPENDING_CATS: Drug Abuse (NIDA only);Neurosciences;Substance Misuse

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: PROJECT NARRATIVE/HEALTH RELEVANCE The major health problems in the US result from brain diseases, including Alzheimer's, schizophrenia, alcoholism, drug addiction, depression and bipolar disorders. Incomplete understanding of the neuroscience of these conditions accounts for the limited number of effective treatments. The goal of this proposal is to provide state-of-the-art training for the next generation of neuroscientists who are equipped to solve these health problems.

PI_NAMEs: GOLDING, NACE L;LEE, AMY  (contact)

PROJECT_TERMS: Neurosciences;pre-doctoral;Training

PROJECT_TITLE: Pre-Doctoral Training in Interdisciplinary Neuroscience


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Dissemination and Implementation Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Pediatric;Pediatric - AIDS;Prevention;Screening and Brief Intervention for Substance Misuse;Social Determinants of Health;Substance Misuse;Underage Drinking

ORG_STATE: NY

PHR: The proposed research has significant public health relevancy because improved alcohol screening in HIV care settings in sub-Saharan Africa (SSA) has the potential to improve rates of referral to evidence-based services, reduce the alcohol treatment gap, and therefore reduce the deleterious impacts of alcohol on HIV prevention and treatment outcomes. This study will describe test characteristics of UEtG in a novel population of HIV-affected adolescents and young adults in SSA and will inform the development of implementation strategies to enhance the adoption and uptake of alcohol biomarkers in HIV clinics. Given the lack of alcohol biomarker studies among adolescents in HIV programs worldwide, this study will provide knowledge cross-over to high-income countries to improve quality of care among minority, and other underserved populations.

PI_NAMEs: KANE, JEREMY CALVIN (contact)

PROGRAM_OFFICER_NAME: ROACH, DEIDRA

PROJECT_TERMS: Achievement;Address;Adherence;Adolescent;Adolescent and Young Adult;Adoption;Affect;Africa South of the Sahara;Age;AIDS prevention;Alcohol abuse;alcohol abuse therapy;Alcohol consumption;alcohol epidemiology;alcohol intervention;alcohol measurement;alcohol misuse;alcohol risk;alcohol screening;alcohol services;alcohol testing;Alcohols;Back;Biological Assay;Biological Markers;Body mass index;brief intervention;career;career development;Caring;catalyst;Cessation of life;Characteristics;Clinic;clinical practice;Clinical Research;Collaborations;Consumption;cost;Counseling;Country;Data Collection;Dedications;design;Detection;Development;Development Plans;Diagnosis;diagnostic tool;Dissemination and Implementation;Ecological momentary assessment;effectiveness evaluation;Effectiveness of Interventions;efficacy study;Epidemic;Evaluation;evidence base;Evidence based practice;experience;feasibility testing;Feedback;Focus Groups;follow-up;Follow-Up Studies;formative assessment;Funding;future implementation;Gender;Glucuronides;Goals;health disparity;high risk sexual behavior;HIV;HIV Infections;HIV/AIDS;Home;implementation determinants;implementation research;implementation science;implementation strategy;implementation/effectiveness;improved;Incidence;Income;Infectious Diseases Research;innovation;Interview;Knowledge;laboratory experience;Lead;Link;Measurement;Measures;Mentors;Mentorship;Methods;Minority;multidisciplinary;National Institute on Alcohol Abuse and Alcoholism;novel;Outcome;Patient Self-Report;phosphatidylethanol;point-of-care diagnostics;Policy Maker;Population;population based;Predisposition;Prevalence;prevention service;Procedures;Process;Professional counselor;programs;Protocols documentation;Psychiatric epidemiology;Public Health;Quality of Care;randomized trial;reduced alcohol use;Religion;Reporting;Research;Research Activity;Research Personnel;Research Training;Resource Allocation;Risk;Role;Scientist;screening;screening and brief intervention;Screening Result;Services;Social Desirability;social stigma;Societies;Strategic Planning;stressor;Test Result;Testing;timeline;Training;transmission process;Treatment Efficacy;Treatment outcome;treatment services;underage drinking;Underserved Population;United States National Institutes of Health;Universities;uptake;Urine;Viral;Visit;Work;Youth;Zambia

PROJECT_TITLE: Improving measurement of alcohol consumption among HIV-affected youth in sub-Saharan Africa: evaluation and implementation of biomarkers


NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Estrogen;Genetics;Women's Health Research

PHR: PROJECT NARRATIVE Tumors that express estrogen receptor-α (ER+) make up the largest subclass of breast tumors, and account for most breast cancer mortalities. This proposal focuses on the control of ER activity, leveraging receptor post-translational regulation as a means to better define and ultimately control ER function in ER+ therapy-resistant breast cancers.

PI_NAMEs: FOWLER, AMY  (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: Ablation;Address;Affinity;Aromatase Inhibitors;Binding;Binding Sites;Biology;bone;Breast Cancer Cell;Breast Cancer Patient;cancer biomarkers;Cancer Cell Growth;cell growth;Cell model;Cells;ChIP-seq;Clinical;Clinical Management;Clustered Regularly Interspaced Short Palindromic Repeats;cofactor;cohort;Data;Development;Dimerization;Distant;DNA;DNA Binding;DNA Microarray Chip;DNA Sequence Alteration;DNA-Binding Proteins;Enhancers;ESR1 gene;Estrogen decline;Exhibits;Family;Fulvestrant;Gene Expression;Genes;Genetic;Genetic Transcription;genome-wide;Genomics;Glucagonoma;Growth;hormone therapy;Impairment;In Vitro;in vivo;Informal Social Control;inhibitor;Knock-in;Knowledge;Ligand Binding;Ligand Binding Domain;Ligands;Link;Lung;Malignant Breast Neoplasm;Malignant Neoplasms;malignant phenotype;Mammary Neoplasms;Mediating;member;mortality;mutant;Mutation;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;Nuclear Receptors;Outcome;Paracrine Communication;Patients;Peptide Nucleic Acids;Phosphorylation;Play;Post-Translational Regulation;Proliferating;Property;Proteins;Publications;Publishing;receptor;receptor function;recruit;Recurrence;Recurrent tumor;Refractory;refractory cancer;Regulation;Research;Resistance;response;Role;Sampling;Serine;Signal Transduction;Site;Specificity;Structure;Tamoxifen;targeted treatment;Technology;Testing;therapy resistant;Time;Transactivation;transcription factor;tumor;Tumor Cell Biology;tumor microenvironment;Tumor Subtype;Variant;Woman

PROJECT_TITLE: Mechanisms of Variant ER-alpha Function in Breast Cancer

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Program Director/Principal Investigator (Last, First, Middle): GUAN, JIANJUN Project Narrative: Diabetic patients with critical limb ischemia have significantly high rates of limb amputation and mortality. Yet there is no effective therapy available. Accomplishment of this project will develop a novel protein based therapy capable of simultaneously regenerating vasculature and skeletal muscles in diabetic ischemic limbs, leading to functional improvement. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

PI_NAMEs: GUAN, JIANJUN  (contact);ZHANG, FUZHONG

PROGRAM_OFFICER_NAME: DANTHI, NARASIMHAN

PROJECT_TERMS: Acceleration;angiogenesis;blood perfusion;Blood Platelets;Cell membrane;cell motility;Cell Physiology;Cell Survival;Cellular Metabolic Process;Clinical;controlled release;critical limb Ischemia;density;diabetic;Diabetic mouse;diabetic patient;Diameter;Diffusion;effective therapy;efficacy testing;Encapsulated;Endothelial Cells;Endothelium;Engineering;Environment;Exhibits;Fibrosis;functional improvement;Glucose;Growth Factor;Hyperglycemia;Impairment;improved;Inferior;Inflammation;Injections;innovation;Ischemia;limb amputation;limb ischemia;Limb Salvage;Limb structure;Membrane;migration;Modeling;Morphogenesis;mortality;Mus;Muscle Cells;Muscle Fibers;Muscle function;Muscle satellite cell;Myoblasts;myogenesis;nanoparticle;Natural regeneration;novel;novel strategies;Peptides;Phosphotransferases;preservation;Principal Investigator;programs;Proliferating;Property;Protein Engineering;Proteins;repaired;Reporting;Signal Pathway;Skeletal Muscle;targeted delivery;Testing;Therapeutic Effect;Time;Tissues;Treatment Efficacy;Tube;Vascularization

PROJECT_TITLE: Targeted delivery of a proangiogenic and promyogenic protein for regeneration of diabetic ischemic limbs


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

PHR: Project Narrative Functional recovery from stroke determines the patients’ quality of life. The goal of the proposed project is to unravel the cortical circuit mechanisms underlying functional recovery after stroke. We will employ innovative approaches using state-of-the-art two-photon imaging techniques combined with optogenetic stimulation in mice. Our proposed study will provide pivotal information on how we can manipulate cortical circuits to maximize functional recovery following stroke.

PI_NAMEs: SATO, TAKASHI  (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Address;Affect;Area;Axon;axonal sprouting;Behavior;Behavioral Paradigm;Brain;cell type;Cells;Consensus;Contralateral;Corpus striatum structure;Data;disability;effective intervention;Electroporation;Enterobacteria phage P1 Cre recombinase;frontal lobe;Future;Goals;Head;hippocampal pyramidal neuron;Image;Imaging Techniques;improved;in vivo calcium imaging;in vivo two-photon imaging;inhibitory neuron;innovation;Interneurons;Investigation;Ipsilateral;Label;Left;Long term disability;Mediating;Monitor;Motor Cortex;motor recovery;Movement;Mus;neural circuit;Neurons;novel strategies;optogenetics;Parvalbumins;Patients;Pattern;Performance;post stroke;Presynaptic Terminals;Process;Quality of life;Recovery;Recovery of Function;Rehabilitation therapy;Research;Role;Side;Site;Somatosensory Cortex;Somatostatin;Spinal Cord;Stroke;stroke recovery;Testing;Time;Training;two-photon;United States;Vasoactive Intestinal Peptide;Visualization

PROJECT_TITLE: Cortical Circuits Underlying Functional Recovery Following Stroke

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Data Science;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Narrative The emerging spatial molecular profiling technology enables the comprehensive molecular characterization of cells while preserving their spatial contexts. The goal of this proposed study is to develop novel algorithms and bioinformatics tools to analyze spatial molecular profiling data, in order to characterize molecular spatial organizations and associate them with cellular phenotypes and disease status.

PI_NAMEs: XIAO, GUANGHUA  (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Algorithmic Software;Algorithms;Attention;Bayesian Modeling;bioinformatics tool;Biological;Biological Process;biological research;Cell Physiology;cell type;Cells;Characteristics;Clinical;Communities;Complex;complex data;Computational algorithm;computerized tools;Computing Methodologies;Data;Data Analyses;Data Set;data structure;data visualization;deep learning;deep learning algorithm;Development;Disease;disease classification;disease diagnosis;Embryonic Development;empowerment;experience;Feasibility Studies;feature selection;flexibility;Gene Expression;Genes;Goals;Graph;graph neural network;Heterogeneity;Image;Image Analysis;improved;informatics tool;Infrastructure;insight;Intuition;Lead;Location;Machine Learning;mental function;Messenger RNA;Methodology;Methods;Modeling;Molecular;Molecular Profiling;Morphology;Network-based;novel;Pathologic;Pathway interactions;Patient-Focused Outcomes;Pattern;Phenotype;Physiological;preservation;Proteins;Research;Research Personnel;single cell genomics;software development;Spatial Distribution;Statistical Methods;Statistical Models;Structure;Technology;Tissue imaging;Tissues;tool;tumor heterogeneity;user friendly software;Variant;Visualization

PROJECT_TITLE: Developing novel algorithms for spatial molecular profiling technologies

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


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

ORG_CITY: Aurora

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Myelin repair is critical for restoring function in multiple sclerosis (MS) patients. This project uses novel ex vivo and in vivo models of demyelination/remyelination induced by recombinant antibodies cloned from MS patients to investigate the role of microglia in oligodendrocyte maturation and myelin repair.

PI_NAMEs: BENNETT, JEFFREY L;MACKLIN, WENDY B (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Animal Model;Antibodies;Antibody Therapy;Autoantibodies;Brain;CCL2 gene;Cells;Central Nervous System;central nervous system demyelinating disorder;central nervous system injury;Cerebrospinal Fluid;Chronic;Clinical;clinically relevant;Clonal Expansion;Complement;Corpus Callosum;Cuprizone;Data;Demyelinations;Exposure to;functional restoration;Gene Expression Profile;Genes;Genetic Transcription;glial activation;glycoprotein NMB;gray matter;Human;IGF1 gene;Image;Immune response;Immunoglobulin G;Impairment;In Situ;in vivo;in vivo imaging;in vivo Model;Incubated;Inflammatory;Infusion procedures;Injections;Injury;injury and repair;insight;intravital imaging;Investigation;Knowledge;Lesion;Lysophosphatidylcholines;Mediating;Microglia;Microinjections;Modeling;Monitor;multi-photon;Multiple Sclerosis;Multiple Sclerosis Lesions;multiple sclerosis patient;Myelin;Natural regeneration;Nervous System;Nervous System Physiology;Nervous System Trauma;Neuroglia;Neurological disability;neurotransmission;novel;novel therapeutic intervention;oligodendrocyte progenitor;Oligodendroglia;Pathogenicity;pharmacologic;Plasma Cells;prevent;Process;Production;Recombinant Antibody;Recovery;remyelination;repaired;response;Role;selective expression;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Slice;Testing;Thalamic structure;therapy design;Time;Tissues;Toxin;Visualization;white matter

PROJECT_TITLE: Microglial impact on remyelination

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


ORG_CITY: PHILADELPHIA

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: NARRATIVE The principal aims of the Training Program in Demography at the University of Pennsylvania accord with the NICHD Population Dynamics Branch’s (PDB) mission to support research and research training in demography, reproductive health, and population health. In particular, training in demography as proposed in this application is essential for research on morbidity and mortality, COVID-19, HIV/AIDS, fertility, families, population movement, and population composition that is central to the PDB mission. The Training Program in Demography at Penn builds on a strong faculty, dedicated students, and an impressive group of alumni to maintain its ongoing relevance to the mission of NICHD, which is “to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all.”

PI_NAMEs: GUILLOT, MICHEL  (contact)

PROGRAM_OFFICER_NAME: CAPPS, RANDOLPH CHRISTOPHER

PROJECT_TERMS: Demography;Training

PROJECT_TITLE: Graduate Training in Demography


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Pediatric;Prevention;Rare Diseases

PHR: Project Narrative Narrowing or leakage of the valves in the heart is common and can be addressed by repairing or replacing the valve. However, the optimal timing of these procedures is difficult to determine, and if performed too late then the heart may be irreversibly damaged. In this proposal we will develop new imaging techniques to detect very subtle changes in the heart muscle and determine whether they can be used to better understand when to replace/repair damaged heart valves.

PI_NAMEs: MEKKAOUI, CHOUKRI ;NGUYEN, CHRISTOPHER T;SOSNOVIK, DAVID E (contact)

PROGRAM_OFFICER_NAME: EVANS, FRANK

PROJECT_TERMS: Address;Air;Anisotropy;aortic valve;Aortic Valve Insufficiency;Aortic Valve Stenosis;Attention;Biological Assay;Biological Markers;Blood;Breathing;Cardiac;Cardiac Myocytes;Catheters;Cells;Clinical;Code;Compensation;Coupled;Data;Data Set;denoising;Development;Diffusion;Diffusion Magnetic Resonance Imaging;Disease;Early Diagnosis;Early Intervention;Early treatment;EFRAC;Elements;Excision;exosome;extracellular vesicles;Extravasation;Fibrosis;Functional disorder;Genotype;Health;Heart;heart damage;Heart failure;Heart Valve Diseases;Heart Valves;Hematopoietic;hemodynamics;Hypertrophy;Image;imaging approach;Imaging Techniques;improved;improved outcome;in vivo;Inferior;innovation;insight;interest;Investigation;Joints;Knowledge;Lateral;Left;Left Ventricular Ejection Fraction;Left Ventricular Hypertrophy;Left ventricular structure;Magnetic Resonance Imaging;Measures;mechanical load;Medical;member;minimally invasive;Mitral Valve;Mitral Valve Insufficiency;Mitral Valve Prolapse;Modeling;Modification;Motion;mRNA sequencing;multitask;Muscle Cells;Myocardial;Myocardium;novel;novel marker;novel strategies;Patients;Pattern;Phenotype;physical property;Physiologic pulse;Play;preservation;pressure;pro-brain natriuretic peptide (1-76);Procedures;Proteins;Public Health;radio frequency;reconstruction;repaired;Resolution;response;Risk Assessment;Risk Marker;RNA;Role;Scanning;Scheme;Serology;Signal Transduction;Stenosis;Stress;Structure;Study Subject;Surface;Techniques;Testing;Time;Tissues;tool;transcriptome;transcriptome sequencing;Troponin;ultra high resolution;valve replacement;Variant;Ventricular;Vesicle

PROJECT_TITLE: Microstructural Response of the Myocardium to Mechanical Load

STUDY_SECTION: EITA

STUDY_SECTION_NAME: Emerging Imaging Technologies and Applications Study Section[EITA]


NIH_SPENDING_CATS: Infectious Diseases;Sleep Research

PHR: PROJECT NARRATIVE My lab studies circadian-regulated processes and their contributions to health and disease; circadian regulation refers to daily oscillations in biological functions (e.g., metabolism, sleep) and is a universal, evolutionarily conserved feature from bacteria to humans. Proper circadian regulation is important for human health; despite the profound effects of circadian regulation on human health and physiology, it remains unclear how loss of circadian regulation contributes to the progression of disease (i.e., metabolic disorders, bacterial infection). In this proposal, we focus on circadian-regulated metabolism in Drosophila and its role in sensitivity to oxidative stress due to chronic short sleep (Project 1) and regulation of host tolerance of bacterial infection (Project 2).

PI_NAMEs: SHIRASU-HIZA, MICHELE M (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Bacteria;Bacterial Infections;Behavioral;Biological Process;Burkholderia cepacia;Chronic;circadian;Circadian Dysregulation;circadian pacemaker;circadian regulation;Circadian Rhythms;Data;Defect;Defense Mechanisms;Disease;Disease Progression;Drosophila genus;Feedback;Funding;Genes;Genetic Transcription;Health;Hour;Human;Immunity;Infection;Innate Immune Response;Investigation;Jet Lag Syndrome;Knowledge;lipid metabolism;Mammals;Mediating;Metabolic;Metabolic Diseases;Metabolism;Mus;mutant;National Institute of General Medical Sciences;Natural Immunity;Nervous System Disorder;Oxidative Stress;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Physiological;Physiology;Process;Publishing;Regulation;Research;Resistance;resistance mechanism;Rest;Role;shift work;Sleep;Stimulator of Interferon Genes;Tissues;tool development;Work

PROJECT_TITLE: Circadian regulation of physiological functions


ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE While there have been major biomedical science discoveries over the last two decades, we still face a steady decline in our collective ability to translate these remarkable basic science discoveries into new drugs and treatments for patients. In this training program, we address this challenge directly with a creative approach to training early career physicians and basic scientists in the essential tools for translational patient-oriented research, drug development, and commercialization of basic discoveries. We implement this training in the scientific context of the study of high blood pressure in the lungs, an important and common complication of many heart and lung diseases.

PI_NAMEs: SHIVA, SRUTI  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TITLE: Training in Translational Research in Pulmonary Vascular Biology

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(JA)]


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CITY COLLEGE OF NEW YORK

PHR: Project Narrative Severe spinal cord injury (SCI) remains incurable as there are no medications that can reverse the injury- related nerve tissue damage through a sustained program of neuroregeneration. We have identified several small molecule compounds able to promote the regrowth of damaged nerve cells in a tissue culture model. The mechanism of action of these nonpeptide neurotrophic compounds appears to be novel and as such we plan to elucidate the mechanism and subsequently apply the knowledge gained toward repurposing existing drugs or designing new compounds for regenerative treatment of SCI.

PI_NAMEs: UNDIEH, ASHIWEL S (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Acceleration;Amitriptyline;Anabolism;Animal Model;Axon;axon injury;Behavioral;Biochemical;Biological;Biological Assay;Blood Circulation;Brain;Brain-Derived Neurotrophic Factor;Cell membrane;Cell Proliferation;Cell Survival;Cervical;Chemicals;Contusions;Corticospinal Tracts;Cytidine Diphosphate Diglycerides;design;Development;Disease;drug candidate;Drug Kinetics;efficacy evaluation;Endoplasmic Reticulum;experimental study;Exposure to;Fluoxetine;Goals;Growth;Growth Factor;healing;Human;In Vitro;Injury;Knowledge;Laceration;Lead;Ligands;Link;Mechanics;Mediating;Mediator;member;Membrane;Modeling;Motor;Natural regeneration;nerve damage;Nerve Growth Factors;nerve injury;Nerve Regeneration;nerve stem cell;Nerve Tissue;neural;neural growth;neuronal survival;Neurons;neurotrophic factor;Neurotrophic Tyrosine Kinase Receptor Type 2;novel;Outcome;Paralysed;Pathway interactions;Peripheral;Pharmaceutical Preparations;pharmacologic;Phenotype;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Phospholipase C;Phosphorylation;PIK3CG gene;Preparation;Program Sustainability;programs;Proliferating;Property;Protein Isoforms;Ras Signaling Pathway;Rattus;receptor;Receptor Activation;Receptor Signaling;Recovery;Recovery of Function;Recycling;regenerative;regenerative repair;regenerative treatment;repaired;Research;Resistance;Role;Sampling;screening;Sensory;Signal Transduction;SKF38393;Slice;small molecule;Spinal Cord;Spinal cord injury;Spinal cord injury patients;spinal cord repair;Testing;Therapeutic;tissue culture;Tissues;translational approach;Traumatic injury;uptake;Work

PROJECT_TITLE: Nonpeptide Neurotrophic Mechanisms in Spinal Cord Repair


ORG_DEPT: PHARMACOLOGY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Unscheduled whole-genome doubling events give rise to genetically unstable polyploid cells that can promote disease. The aims of this proposal are designed to identify unique the genetic adaptations acquired by polyploid cells that enable their sustained proliferation and survival. Successful completion of these aims will provide significant insight into the genesis and evolution of whole genome-doubled cells in vivo, as well as reveal innovative therapeutic avenues to selectively kill pathological polyploid cells while sparing the normal cells that comprise human tissue.

PI_NAMEs: GANEM, NEIL J. (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Affect;Aging;Animal Model;Animals;Area;Biological;Biological Models;Biology;cancer cell;Cell Line;Cell model;Cell Proliferation;Cell Survival;Cells;Cellular biology;Chromosome abnormality;Chromosomes;Computer Analysis;Computer Models;CRISPR-mediated transcriptional activation;Cues;Data;Defect;Dependence;design;Development;Diploid Cells;Diploidy;Disease;Epithelial Cells;Event;Evolution;Frequencies;Gene Amplification;Gene Deletion;Generations;Genes;Genetic;Genome;Genomics;Goals;Growth;Hepatocyte;Human;human disease;human tissue;Image;In Vitro;in vivo;Incidence;innovation;insight;Kinesin;Knockout Mice;Lethal Genes;Maintenance;Malignant Neoplasms;Methodology;Mitotic;mouse model;Mutation;Nature;neoplastic cell;new therapeutic target;Normal Cell;overexpression;Pathologic;Pathway interactions;Phenotype;Physiological;Play;Ploidies;Polyploid Cells;Polyploidy;Primary Neoplasm;Proliferating;Repression;Research;Role;Route;screening;small molecule inhibitor;Solid Neoplasm;Testing;Therapeutic;Tissues;Transgenic Mice;tumor;Tumor Subtype;tumorigenesis;Variant;Vertebrates;whole genome;Work

PROJECT_TITLE: Mechanisms of cell proliferation in whole-genome doubled cells

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


NIH_SPENDING_CATS: Biotechnology;Genetics;Natural Products

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE The soil-dwelling bacteria Streptomyces make numerous molecules that humans use as medicines. Analysis of the DNA of these bacteria suggests they have the potential to make many more useful molecules, but they do not make them under standard laboratory conditions. The objectives of this proposal are to 1) discover chemical elicitors that induce the production of these molecules, to understand their mechanisms of induction, and to use these elicitors to identify novel bioactive natural products and 2) to use organic synthesis to access bioinformatically predicted natural products that are currently inaccessible using other means.

PI_NAMEs: PARKINSON, ELIZABETH IVY (contact)

PROJECT_TERMS: Antibiotics;anticancer activity;antimicrobial;Antineoplastic Agents;Bacteria;bioactive natural products;Bioinformatics;Cell Membrane Permeability;chemical synthesis;Chemicals;Coculture Techniques;Communities;Cyclic Peptides;Distant;DNA analysis;Family;FDA approved;Gene Cluster;Genes;Genetic Transcription;genome sequencing;Goals;Human;Laboratories;Libraries;Medicine;Methods;microorganism;Mining;Natural Products;novel;Organic Synthesis;peptide natural products;peptide synthase;Peptides;Pharmaceutical Preparations;Production;protein protein interaction;Regulation;Signal Transduction;small molecule;Soil;Source;Streptomyces;Techniques;tool;Work

PROJECT_TITLE: Mining Cryptic Biosynthetic Gene Clusters for Novel Bioactive Compounds

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