NIH_SPENDING_CATS: Biotechnology;Precision Medicine

ORG_CITY: MINNEAPOLIS

PHR: Project Narrative From parent project: Kinase inhibitor drugs have changed the face of therapeutics and are projected to remain a major focus of drug development, however, their long-term efficacy is variable because of biological complexity and resistance. We are developing assay strategies that can be used to study kinase signaling biology, and screen new drugs and drug combinations in a way that better mimics biological complexity. These could someday also be used as companion diagnostics for the drugs they help discover, to monitor the effectiveness of treatment, finding resistance earlier so patients can try alternatives that could improve their treatment outcomes. References Jumper, J., R. Evans, A. Pritzel, T. Green, M. Figurnov, O. Ronneberger, K. Tunyasuvunakool,  R. Bates, A. Zidek, A. Potapenko, A. Bridgland, C. Meyer, S. A. A. Kohl, A. J. Ballard, A.  Cowie, B. Romera-Paredes, S. Nikolov, R. Jain, J. Adler, T. Back, S. Petersen, D. Reiman,  E. Clancy, M. Zielinski, M. Steinegger, M. Pacholska, T. Berghammer, S. Bodenstein, D.  Silver, O. Vinyals, A. W. Senior, K. Kavukcuoglu, P. Kohli, and D. Hassabis. 2021. 'Highly  accurate protein structure prediction with AlphaFold', Nature, 596: 583-89. Tunyasuvunakool, K., J. Adler, Z. Wu, T. Green, M. Zielinski, A. Zidek, A. Bridgland, A. Cowie,  C. Meyer, A. Laydon, S. Velankar, G. J. Kleywegt, A. Bateman, R. Evans, A. Pritzel, M.  Figurnov, O. Ronneberger, R. Bates, S. A. A. Kohl, A. Potapenko, A. J. Ballard, B.  Romera-Paredes, S. Nikolov, R. Jain, E. Clancy, D. Reiman, S. Petersen, A. W. Senior, K.  Kavukcuoglu, E. Birney, P. Kohli, J. Jumper, and D. Hassabis. 2021. 'Highly accurate  protein structure prediction for the human proteome', Nature, 596: 590-96. Widstrom, N. E., G. V. Andrianov, J. L. Heier, C. Heier, J. Karanicolas, and L. L. Parker. 2023.  'Novel Substrate Prediction for the TAM Family of RTKs Using Phosphoproteomics and  Structure-Based Modeling', ACS Chem Biol. Accession Number: 38159292 DOI: 10.1021/acschembio.3c00549

PI_NAMEs: PARKER, LAURIE L. (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Area;assay development;Back;Biological;Biological Assay;Biology;Biomedical Research;career;career development;companion diagnostics;design;Drug Combinations;drug development;experience;Face;Family;Goals;Human;improved;inhibitor therapy;kinase inhibitor;Kinetics;kohl;Mentors;Minnesota;Modeling;Monitor;Nature;novel;novel therapeutics;parent project;Patients;Pharmaceutical Preparations;phosphoproteomics;Phosphotransferases;Postbaccalaureate;programs;protein structure prediction;Proteome;Proteomics;Research;research and development;Research Project Grants;Resistance;scaffold;Signal Transduction;Silver;skills;Structure;Students;Testing;Therapeutic;Training;Treatment Effectiveness;Treatment outcome;Universities;Work

PROJECT_TITLE: Multiplexed proteomics-based kinase assay development

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


ADMINISTERING_IC: AG

ARRA_FUNDED: N

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: WOODSIDE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: LIFE ANALYTICS, INC.

ORG_STATE: CA

PHR: Project Narrative: Alzheimer’s disease and Alzheimer’s disease-related dementia (AD/ADRD) are characterized by severe dementia that interferes with daily tasks, reduced memorization abilities, poor behavior, and inability to think clearly and afflicts nearly 6 million Americans 65 years and older. Clinical trials addressing AD/ADRD require large patient cohorts and are notorious for failures with over 400 unsuccessful attempts last decade. In this proposal, we further develop a non-invasive, at-home AD/ADRD patient monitoring platform that will provide continuous and quantitative measurements of health related biomarkers which in turn will improve the efficiency of clinical trials by providing high-frequency data to inform go/no-go decisions.

PI_NAMEs: FRYE, LAWRENCE J (contact)

PROGRAM_OFFICER_NAME: HARRELL, ERIN

PROJECT_TERMS: Address;African American;Aging;aging and technology;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;American;associated symptom;Back;Behavior;Biological Markers;Caring;checkup examination;Clinical;Clinical Research;Clinical Trials;cohort;commercialization;Communities;Computer software;Conduct Clinical Trials;Data;Data Collection;data exchange;data platform;Dementia;Development;digital;Disease;Disease Progression;Elderly;Failure;Frequencies;Funding;Health;Home;improved;Infrastructure;Latinx population;Life;Life Style;Location;Longitudinal Studies;Measurement;Measures;Medical;Memory;migration;Modeling;Monitor;North America;Oregon;Patient Monitoring;Patient Self-Report;Patients;Phase;Provider;Publications;remote assessment;Research;research and development;Rural Community;Secure;Site;System;Technology;technology platform;Testing;United States National Institutes of Health;usability

PROJECT_TITLE: Optimization of an at-home continuous multi-domain monitoring and assessment system to improve Alzheimer's and related disorders clinical trials


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research

ORG_CITY: LA JOLLA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative - No change from original application  African Americans have the highest incidence and mortality rates from colorectal cancer over any other major racial or ethnic group in the United States, but it is not fully clear what drives the aggressiveness of disease in these patients. We discovered that pro-inflammatory cytokines like IL6 are persistently released during inflammation and directly impede specific repair processes centered around the DNA mismatch repair protein MSH3 such that subsequent mutations within DNA accumulate, and associates with poor patient outcome. We aim to understand the contribution of MSH3 dysfunction to the poor survival outcome of African American colorectal cancer patients.

PI_NAMEs: ASHKTORAB, HASSAN ;CARETHERS, JOHN M (contact)

PROGRAM_OFFICER_NAME: SHARMAN, ANU

PROJECT_TERMS: 9p24;Affect;African American;African American population;Aneuploidy;Applications Grants;Area;Back;Biological Markers;Caucasians;cell behavior;Cell Line;Cell Nucleus;Chromosomes;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;colon cancer patients;Colon Carcinoma;Colorectal Cancer;Copy Number Polymorphism;Coupled;cytokine;Cytosol;Data;Death Rate;Defect;digital;Disease;Disparity;DNA;DNA Damage;DNA Double Strand Break;DNA Modification Process;DNA Repair;Ethnic Origin;Ethnic Population;Frequencies;Functional disorder;Generations;Genes;Genetic Diseases;homologous recombination;Incidence;Inflammation;Inflammatory;innovation;Interleukin-6;Joints;loss of function;Loss of Heterozygosity;Microsatellite Repeats;mismatch repair protein 1;Molecular and Cellular Biology;mortality;MSH3 gene;Mutation;neoplastic;novel;Nuclear;Patient-Focused Outcomes;Patients;Phenotype;prevent;Process;protein function;Proteins;public database;Publications;Race;racial population;Rectal Cancer;repair function;repaired;Reporting;Role;survival outcome;Techniques;Tetranucleotide Repeat;Time;United States

PROJECT_TITLE: Inactivation of MSH3 in Colorectal Cancer and Race

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Infant Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect that can lead to death of newborns within a week in the absence of surgical treatment. This R01 project aims to address how the aberrant intercellular communication between myocardium (cardiac muscle fibers) and endocardium (endothelial cells lining the interior of the heart) leads to HLHS using patient-derived induced pluripotent stem cells and CRISPR genome editing. Understanding how HLHS is developed would be pivotal to discover novel therapeutic treatment for this lethal disease.

PI_NAMEs: ZHAO, MINGTAO  (contact)

PROGRAM_OFFICER_NAME: LI, HUIQING

PROJECT_TERMS: access restrictions;Address;Affect;Animal Model;Animals;aortic valve;aortic valve disorder;Aortic Valve Stenosis;ascending aorta;Cardiac;Cardiac Myocytes;cardiogenesis;Cell Line;Cells;Clinical;clinical phenotype;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Communication;congenital heart abnormality;Congenital Heart Defects;CRISPR/Cas technology;Data;Defect;design;Development;Disease;Electrophysiology (science);Elements;Embryo;Endocardium;Endothelial Cells;Endothelium;exosome;Gene Dosage;Generations;Genetic;Genetic Engineering;genome editing;Genotype;Growth;Heart;Heart Atrium;Heart Diseases;Human;human induced pluripotent stem cells;human stem cells;Hypoplastic Left Heart Syndrome;induced pluripotent stem cell;induced pluripotent stem cell derived cardiomyocytes;intercellular communication;Interruption;Knowledge;Lead;Left;Left ventricular structure;Link;Mediating;Mitral Valve;Molecular;Morphogenesis;mouse model;Muscle Fibers;Mutation;Myocardial;Myocardium;Neonatal Mortality;Newborn Infant;Nodal;notch protein;NOTCH1 gene;novel;novel therapeutics;Operative Surgical Procedures;patch clamp;Pathogenicity;patient derived induced pluripotent stem cells;Patients;prevent;Proliferating;Proteomics;Publishing;Running;Side;Signal Transduction;single-cell RNA sequencing;Small RNA;stem cell model;stem cells;Structural defect;Structure;Study models;System;transcriptome sequencing;Variant;Ventricular

PROJECT_TITLE: An integrated human stem cell model for elucidating myocardial-endocardial interactions in cardiac development and disease

STUDY_SECTION: CCHF

STUDY_SECTION_NAME: Cardiac Contractility, Hypertrophy, and Failure Study Section[CCHF]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics;Human Genome;Pediatric

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: Project Narrative Cells must inherit the right number of chromosomes every time they divide. Defects in this process are the most common chromosomal abnormality in cancer cells and contribute to birth defects and other diseases. We are therefore studying the process of chromosome distribution to daughter cells when they divide to understand the basis for a number of human diseases.

PI_NAMEs: BIGGINS, SUSAN  (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Aneuploidy;Biochemical;cancer cell;Cell Cycle;Cell Cycle Regulation;Cell division;Cells;Centromere;Chromosome abnormality;Chromosome Segregation;Chromosomes;Congenital Abnormality;Cytology;daughter cell;Defect;Development;Disease;Ensure;Eukaryota;Evolution;Genetic;Genome Stability;Human;human disease;in vitro Assay;Inherited;Kinetochores;Lead;Malignant Neoplasms;Microtubules;Organism;prevent;Process;Proteins;Saccharomycetales;Spontaneous abortion;Time;Weight-Bearing state;Work;Yeasts

PROJECT_TITLE: Diversity Supplement: Mechanisms underlying chromosome segregation


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Injury;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Patient Safety;Pediatric;Physical Injury - Accidents and Adverse Effects;Prevention;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research;Youth Violence;Youth Violence Prevention

ORG_CITY: HOUSTON

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE The long-term outcomes of and the factors that increase or decrease the likelihood of individuals experiencing dating violence are poorly understood. Most of our information comes from cross-sectional studies, which prevents us from knowing whether a particular variable precedes or follows dating violence. The current proposal will extend an ongoing study of dating violence, ultimately resulting in 15 years of (multi-informant) data on over 1,000 ethnically diverse participants and their current partners as they transition from adolescence to young adulthood.

PI_NAMEs: TEMPLE, JEFF R (contact)

PROGRAM_OFFICER_NAME: GILBERT, LEAH KAYE

PROJECT_TERMS: Acute;Address;Adolescence;Adolescent;Adult;Adverse event;adverse outcome;African American;Age;Age Years;Aggressive behavior;Algorithms;American;Behavior;bullying;Child;Child Abuse;child and adolescent victimization;Child Rearing;Childhood;Chronic;cohort;Cross-Sectional Studies;Data;Data Collection;dating violence;dating violence prevention;Development;Education;Electronics;emerging adult;emotional abuse;ethnic diversity;Ethnic Origin;experience;Exposure to;Failure;Female;follow-up;Funding;Future;Generations;Happiness;Health;high risk sexual behavior;High School Student;Hispanic;Individual;informant;Intervention;intimate partner violence;Life;Literature;Longitudinal Studies;male;Marriage;Measurement;Measures;Mental Health;Occupational;Occupations;Outcome;Paper;Participant;Patient Self-Report;Peer Review;perpetrators;physical abuse;physical conditioning;prevent;Prevention;Prevention program;Problem behavior;prospective;protective factors;Psyche structure;psychosocial;Public Health;Race;recruit;Research;Risk;Risk Factors;Sampling;sex;Sex Orientation;Sexting;Sexual abuse;Sexuality;social media;Socioeconomic Status;socioeconomics;Subgroup;Substance abuse problem;substance use;suicidal;Teen Dating Violence;Teenagers;tenth grade;Time;treatment program;Victimization;Violence;violence exposure;violence perpetration;violence victimization;young adult

PROJECT_TITLE: A longitudinal study of the outcomes, risk factors, and protective factors of dating violence and other adverse events

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Adolescent Sexual Activity;Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Depression;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Violence Research;Youth Violence;Youth Violence Prevention

PHR: PROJECT NARRATIVE To better understand the short- and long-term impact of the COVID-19 pandemic on youth mental, behavioral, and social health, we will leverage our existing longitudinal study that began prior to the pandemic. In addition to continuing to measure adolescent health, we will assess educators and parents to obtain a comprehensive and rich understanding of factors that mitigated or exacerbated the impact of COVID-19 and resulting disruptions to school, family, and development.

PROGRAM_OFFICER_NAME: KING, ERIN MICHELE

PROJECT_TERMS: 21 year old;Academic achievement;Adolescent;adolescent health;African American;Age;Anxiety;Asian;Award;Behavioral;behavioral health;Black race;career;Climate;cohort;college;Communities;Conflict (Psychology);conflict resolution;coping;Coping Skills;COVID-19 impact;COVID-19 pandemic;COVID-19 pandemic effects;cyberbullying;Data;dating violence;design;Development;digital divide;Dropout;economic disparity;Economics;Education;educational atmosphere;Educational Curriculum;Educational Status;Equity;Event;experience;Exposure to;Family;Female;follow up assessment;follow-up;Food Access;Future;future pandemic;Health;Health behavior;Health behavior and outcomes;help-seeking behavior;Hostility;Housing;housing instability;Hybrids;improved;Income;Individual;Instruction;intergenerational;Interruption;Intervention;intervention program;Interview;Investigation;Job loss;junior high school;Latinx;Learning;Link;long term consequences of COVID-19;long term COVID-19 pandemic impacts;Longitudinal Studies;mass shooting;Measurement;Measures;media use;Mental Depression;mental development;Mental Health;Methods;Modeling;National Institute of Mental Health;Natural Disasters;neighborhood disadvantage;neighborhood safety;Neighborhoods;Occupations;Outcome;pandemic disease;pandemic stressor;Parent-Child Relations;parental role;Parents;Participant;partner violence;Performance;Persons;post-pandemic;Prevention program;programs;prospective;protective factors;Psyche structure;racial disparity;Randomized;Randomized, Controlled Trials;recruit;Risk;Risk Behaviors;Risk Factors;risk sharing;school disruption;Schools;Sex Behavior;social;Social isolation;Socioeconomic Status;Source;stay-at-home order;Stress;Students;substance misuse;substance use;suicidal;Surveys;teacher;Texas;twelfth grade;vaccine acceptance;War;Well in self;Youth

PROJECT_TITLE: Prospective intergenerational mixed-methods investigation of the short- and long-term impact of COVID-19 on adolescent mental, social, and behavioral health

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


ADMINISTERING_IC: DD

IC_NAME: NATIONAL CENTER ON BIRTH DEFECTS AND DEVELOPMENTAL DISABILITIES

ORG_CITY: CHICAGO

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

ORG_STATE: IL

PHR: NARRATIVE The overall objective of the project described in this application will be to collect natural history data at 26 FXS Clinics in the USA, from 600 individuals with FXS born between 2003-2017, including longitudinal data from half the cohort. Data will be used for analyses that will lead to a better understanding of the impact of earlier diagnosis, services received, and medical/social issues, on later cognitive, behavioral, and adaptive function. This will inform public health policy, service delivery recommendations, and will provide longitudinal data to inform outcomes for long-term intervention trials in FXS, thus fostering better health, functioning, and quality of life among persons with FXS and their families.

PI_NAMEs: BERRY-KRAVIS, ELIZABETH MARA (contact);ERICKSON, CRAIG ;TARTAGLIA, NICOLE RENEE

PROGRAM_OFFICER_NAME: OGUNFUYI, SHAKIRATU BIOLA

PROJECT_TITLE: Characterizing the Natural History of Fragile X Syndrome to Inform the Development of Intervention,Outcome Measures


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

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

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: PROJECT NARRATIVE The proposed research will create a cis-regulatory map of how Nodal signaling and T-Box transcription factors, affect cell-type specification during somitic mesoderm development. Improvements to high-throughput single-cell technologies and computational methods will be developed to uncover TF interactions during the differentiation of somitic mesoderm in zebrafish. The success of deep learning methods for in silico experiments to predict TF-TF interactions paired with high throughput CRISPR mutagenesis of F0 zebrafish would represent a significant advance toward understanding gene regulation required for development.

PI_NAMEs: MULLEN, ANDREW CARTER (contact)

PROGRAM_OFFICER_NAME: STEIN, KATHRYN K

PROJECT_TERMS: Affect;Anterior;Automobile Driving;Binding;Biology;cell type;Cells;Cellular Assay;Chromatin;Chromosome Mapping;Clustered Regularly Interspaced Short Palindromic Repeats;cofactor;Communication;Computer Models;Computer software;computerized tools;Computing Methodologies;cost;CRISPR/Cas technology;Data;data modeling;data tools;deep learning;deep neural network;Development;Dissection;DNA;DNA Binding;Embryo;Enhancers;experimental study;Family;flexibility;gene discovery;Gene Expression;Gene Expression Regulation;Genes;genetic approach;Genetic Screening;Genetic Transcription;genome-wide;Genomics;improved;in silico;In Situ Hybridization;Knock-out;Knowledge;Learning;Ligands;Link;Maps;Mediating;member;Mesoderm;Methods;Modeling;Mutagenesis;mutant;Mutate;Mutation;network models;neural network;Neural Network Simulation;Nodal;novel;open source;Phenotype;Pilot Projects;Population;programs;promoter;Protein Family;Proteins;receptor;recruit;Regulatory Element;Research;Resolution;Resources;Role;Series;Signal Transduction;single cell technology;single-cell RNA sequencing;Site;skills;Somites;somitogenesis;Specific qualifier value;Specificity;success;syntax;Tail;Testing;Time;Training;Training Programs;transcription factor;Transforming Growth Factor beta;Transforming Growth Factor beta Receptors;Transposase;Undifferentiated;Untranslated RNA;Vertebrates;Visual;Work;Writing;Zebrafish;zebrafish development

PROJECT_TITLE: Uncovering Nodal signaling and transcription factor interactions in somitic mesoderm development using single-cell deep learning methods

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F05-D(21)L]


NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Cardiovascular;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Precision Medicine;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE  Transthyretin V122I, is a highly penetrant mutation for hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) that is common in African Americans and Hispanic Americans. Recent therapies have been approved to treat hATTR-CM, which have led to decreased mortality; thus, understanding who will develop hATTR-CM, accurate identification of V122I carriers and understanding hidden disease burden is important. In this proposal, we examine the population health impact of V122I using polygenic risk scores, machine learning approaches on electronic health records, and patient recall by genotype, which can lead to new population health strategies for heart failure in racial and ethnic minorities.

PI_NAMEs: DO, RON  (contact);NADKARNI, GIRISH NITIN

PROGRAM_OFFICER_NAME: JAQUISH, CASHELL E

PROJECT_TERMS: Address;Adopted;African American population;African ancestry;African Caribbean;Age;American Medical Association;Amyloid;Amyloid deposition;Amyloid Fibrils;biobank;burden of illness;Cardiac;Cardiomyopathies;Cardiovascular system;clinical care;clinical risk;Clinical Trials;Complex;Data;data repository;Deposition;Diagnosis;Diphosphates;Disease;Documentation;Echocardiography;Electronic Health Record;Environment;ethnic disparity;ethnic minority;Future;Genes;Genetic;Genotype;Germ-Line Mutation;Goals;Grant;Health system;Healthcare Systems;Heart failure;heart imaging;Hispanic Americans;Hospitalization;Image;Image Analysis;improved;Individual;Inherited;innovation;insight;Journals;Knowledge;Learning;Link;Machine Learning;Magnetic Resonance;Mediating;Medicine;Methods;Minority Groups;Morbidity - disease rate;mortality;multi-ethnic;multimodal data;multimodality;Mutation;Myocardial;Myocardium;Nuclear;Onset of illness;Patients;Penetrance;Pennsylvania;Phenotype;polygenic risk score;Population;population health;Prealbumin;precision medicine;Qualifying;Quality of life;racial disparity;racial minority;Recontacts;Research;Risk;Risk Factors;risk stratification;scale up;Scanning;screening;Single Nucleotide Polymorphism;Structure;Supportive care;targeted treatment;Technetium;Technetium 99m;Testing;tool;trait;underserved minority;Universities;Work

PROJECT_TITLE: Elucidating hereditary transthyretin-mediated heart failure risk using machine learning, polygenic risk and recall by genotype approaches in African ancestry individuals

STUDY_SECTION: CICS

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


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

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

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Through an organic synthesis of mathematical modeling, machine learning, and single-cell genomics, this project aims to bridges the unmet gap between the “big data” from single-cell genomics and quantitative/predictive modeling in order to address fundamental questions in mammalian cell fate transitions, and to provide potential avenues for regenerative medicine. In particular, I propose to 1) dissect the mechanisms of mammalian cell differentiation, reprogramming, and maintenance through differentiable deep learning frameworks; 2) integrate multi-omics and harmonize short-term RNA velocities with long-term lineage tracing; and 3) build predictive in silico 3D spatiotemporal models of organogenesis.

PI_NAMEs: QIU, XIAOJIE  (contact)

PROGRAM_OFFICER_NAME: SEN, SHURJO KUMAR

PROJECT_TERMS: 3-Dimensional;Address;Architecture;Atlases;Big Data;Biological;biological systems;Caenorhabditis elegans;career development;Cell Differentiation process;Cell model;Cells;Chromatin;Chromium;Collaborations;computerized tools;CRISPR/Cas technology;Cues;Data;Data Set;deep learning;Development;Development Plans;Differential Equation;Digit structure;dynamic system;Embryo;Embryonic Development;Environment;Epigenetic Process;experimental study;field study;Future;Genetic;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hour;Human;improved;in silico;in situ sequencing;in vivo;innovation;insight;kernel methods;Kinetics;Label;Learning;Link;Machine Learning;machine learning algorithm;Maintenance;Mammalian Cell;Maps;mathematical model;Measurement;Measures;Mentors;Metabolic;Methods;Microscopy;Modeling;Modernization;mouse model;multimodality;multiple omics;Mus;neural;neural network;novel strategies;Organic Synthesis;Organogenesis;Pancreas;Paper;Paracrine Communication;Pattern;Phase;Positioning Attribute;prediction algorithm;Predictive Factor;predictive modeling;progenitor;Proteomics;Publishing;Regenerative Medicine;Research;research and development;Research Personnel;RNA;Side;Signal Transduction;simulation;single cell analysis;single cell genomics;single cell technology;single-cell RNA sequencing;skills;spatiotemporal;Statistical Data Interpretation;stem cells;success;Sum;System;Systems Biology;Technology;technology development;Testing;three-dimensional modeling;Time;Tracer;Training;transcription factor;transcriptome;transcriptomics;Universities;vector;Work

PROJECT_TITLE: Predictive modeling of mammalian cell fate transitions over time and space with single-cell genomics

STUDY_SECTION: GNOM

STUDY_SECTION_NAME: Genome Research Study Section[GNOM-G]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Complementary and Integrative Health;Digestive Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: PITTSBURGH

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative: The total body irradiation induced acute gastrointestinal syndrome is mitigated by administration of an engineered probiotic bacterium Lactobacillus-reuteri, LR-IL-22, which anatomically targets the radiation damaged intestinal crypt stem cells to restore intestinal integrity and is superior to systemic/parenteral administration of IL-22. We have demonstrated that intraoral (gavage) of LR-IL-22 mitigates the gastrointestinal syndrome by restoring irradiation-suppressed gene transcription in intestinal stem cells. We will now establish that LR-IL-22 and a new improved version modulates irradiation-induced molecular biologic cell death pathways in intestinal stem cells, preserves their crypt regeneration capacity, and mitigates the irradiation- induced acute GI syndrome.

PI_NAMEs: GREENBERGER, JOEL S (contact)

PROGRAM_OFFICER_NAME: RIOS, CARMEN I

PROJECT_TERMS: Acute;Address;Adhesions;Anatomy;ARNT gene;Aryl Hydrocarbon Receptor;Bacteria;Biological;Biological Containment;Blood Vessels;Cell Death;cell injury;Cells;Chemotactic Factors;Chromosomes;clinical application;Containment;Cytolysis;Data;Drug Delivery Systems;Effectiveness;Engineered Probiotics;Engineering;Environment;experimental study;gastrointestinal;Gastrointestinal tract structure;Generations;Genes;Genetic Transcription;Goals;gut microbiota;Hematopoietic;improved;In Vitro;inducible Cre;interleukin-22;intestinal crypt;Intestines;irradiation;Lactobacillus reuteri;LGR5 gene;Lymphocyte;Lymphoid Cell;Marrow;Measures;Mediating;microbial;Molecular;Molecular Mechanisms of Action;Mus;mutant;Natural regeneration;novel;Oral;Oral Administration;parenteral administration;Pathway interactions;Pharmaceutical Preparations;Phenotype;Plasmids;preservation;prevent;Probiotics;Production;Property;Proteins;Radiation;radiation countermeasure;Radiation induced damage;Radiation Injuries;radiation mitigation;radiation mitigator;Recombinants;Recovery;recruit;Regenerative capacity;response;Role;Safety;safety engineering;Signal Pathway;stem cell niche;stem cells;Syndrome;Testing;Therapeutic;transcriptome sequencing;Translations;Treatment Efficacy;Whole-Body Irradiation;Wild Type Mouse;γδ T cells

PROJECT_TITLE: LR-IL-22 for Mitigation and Management of Radiation Injuries


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: PROJECT NARRATIVE The statistical models to be completed in this project will be of use to the community of scientists working on a wide range of genomic studies of relevance to human health. The work will increase our understanding of the role of genomic change in the functioning of a class of loci known as enhancers, which are important in gene regulation. The project will increase our basic understanding of the functioning of enhancers and will provide the community with powerful models linking genomic variation with phenotypic variation in a phylogenetic context.

PI_NAMEs: EDWARDS, SCOTT V. (contact);FARLEY, EMMA KIRSTEN;LIU, JUN S;SACKTON, TIMOTHY ;TABIN, CLIFFORD J.

PROGRAM_OFFICER_NAME: GILCHRIST, DANIEL A

PROJECT_TERMS: Acceleration;Bayesian Modeling;Biological;Biological Assay;Birds;candidate identification;Chickens;Chromatin;Communities;comparative;comparative genomics;Complex;Data;Data Set;Development;Disease;DNA;Electroporation;Elements;Emu species;Enhancers;Epigenetic Process;epigenetic profiling;Evolution;Exhibits;Flying body movement;Forelimb;Gene Expression;Gene Expression Regulation;Genes;Genetic Diseases;Genetic Enhancer Element;Genetic Polymorphism;Genome;genome sequencing;genome wide association study;genome-wide;genomic signature;genomic variation;Genomics;Genotype;Health;Heterogeneity;high throughput screening;Hindlimb;Human;Human Genetics;improved;in vivo;Lead;Libraries;Limb structure;Link;loss of function;Malignant Neoplasms;Measures;Methods;model development;Modeling;Morphology;Mutation;novel;Nucleotides;Open Reading Frames;Organ;Phenotype;Phylogenetic Analysis;Phylogenetic Pattern;Phylogeny;Play;Population;Population Genetics;predictive modeling;Process;rate of change;Relaxation;Research Personnel;Role;Sampling;Scientist;Sorting;Source;Statistical Methods;Statistical Models;Study models;System;Testing;tool;trait;transcriptome sequencing;Trees;Untranslated RNA;user-friendly;Validation;Variant;whole genome;Work

PROJECT_TITLE: Statistical and high-throughput models of enhancer function and evolution

STUDY_SECTION: GVE

STUDY_SECTION_NAME: Genetic Variation and Evolution Study Section[GVE]


ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative. The proposed studies are focused on new approaches to HIV/AIDS drug development by targeting an HIV-1 accessory protein (Nef) essential for AIDS progression. Successful completion of the proposed work will provide fresh insights regarding the mechanism of action of small molecule drug candidates that induce selective degradation of the Nef protein in HIV-infected cells. These Nef degraders show great promise for development as a new class of anti-HIV therapeutics with the potential to clear HIV-producing reservoir cells, resulting in a functional cure.

PI_NAMEs: SMITHGALL, THOMAS E. (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, GERARD

PROJECT_TERMS: acquired drug resistance;Acquired Immunodeficiency Syndrome;Affect;Anti-Infective Agents;Anti-Retroviral Agents;antiretroviral therapy;antiviral immunity;Apoptosis;Autologous;Binding;Biological Availability;Biology;cancer clinical trial;CD4 Positive T Lymphocytes;Cell Culture Techniques;Cell surface;Cells;Chemicals;Codon Nucleotides;cohort;Complex;Coupled;Cytotoxic T-Lymphocytes;Data;Detection;Development;Down-Regulation;drug candidate;drug development;Drug Industry;Drug Targeting;emerging virus;Event;Evolution;flexibility;Funding;HIV;HIV drug resistance;HIV Infections;HIV-1;HIV/AIDS;Immune;in vivo;Individual;Infection;inhibitor;innovation;insight;interest;Laboratories;latent HIV reservoir;Libraries;Life Cycle Stages;Ligands;Lysine;Maintenance;Mass Spectrum Analysis;Mediating;Molecular Weight;Mutagenesis;mutant;Mutation;National Institute of Allergy and Infectious Disease;nef Protein;novel;novel strategies;novel therapeutic intervention;Nucleotides;Oral;Patients;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;Predisposition;prevent;programmed cell death protein 1;Protac;protein degradation;Proteins;Proteomics;relapse prevention;Reporting;Research;Resistance;resistance mutation;SIV;small molecule;Speed;T-Lymphocyte;T-Lymphocyte and Natural Killer Cell;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Time;transcriptome sequencing;Triplet Multiple Birth;ubiquitin-protein ligase;Variant;Viral;viral rebound;Viral reservoir;Virus Latency;Work

PROJECT_TITLE: Chemical Biology of HIV-1 Nef

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IIDB-X (03)]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: NARRATIVE Funds are requested for partial support of the 2024 11th LASDB Conference to be held in the city of Valparaiso, Chile, in conjunction with the inaugural meeting of the recently created Chilean Society for Developmental Biology (SBDCh) and the first meeting in Latin America of the Pan-American Society for Evolutionary Developmental Biology (PASEDB). This Conference is intended to bring together a diverse group of scientists working on different aspects of Developmental Biology and using different experimental models and technological approaches to better understand the molecular and cellular processes controlling morphogenesis, providing a unique opportunity and format for the exchange of ideas and information and to attract/retain young postdocs and students to join this exciting research area. To provide more opportunities to early career investigators, postdocs and graduate students, we will select from the abstracts both short talks (15 mins) and flash talks (2.5 mins) to further motivate participation and interactions at the poster sessions, and will have a power hour session on career development, a meet-the-speaker session and several round tables / workshops sessions to debate topics of interests related to diversity in science, ethics, challenges of science in Latin America, developmental biology and climate change, outreach and teaching.

PI_NAMEs: OLIVER, GUILLERMO C (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, MAHUA

PROJECT_TERMS: Address;Amaze;American;Animal Model;Area;Argentina;base;Biodiversity;biophysical techniques;career;career development;Cell Physiology;Cells;Chile;Chilean;Cities;climate change;Collaborations;collaborative environment;Communities;comparative;Congresses;Country;Crows;Development;Developmental Biology;Developmental Process;Discipline;Disease;Educational process of instructing;Educational workshop;Embryology;Ensure;Environment;Equilibrium;Ethics;Ethnic Origin;Event;Evolution;experience;Experimental Models;Faculty;Feedback;Fostering;Funding;Funding Opportunities;Gender;Genes;Genetic;Genetic Complementation Test;Genetic Transcription;genomic platform;Goals;graduate student;Health;Hearing;Hour;Human;Imaging Techniques;In Vitro;in vivo;Influentials;interest;International;Laboratories;Latin America;Latin American;Learning;London;Measures;meetings;Microscopy;model organism;Modeling;Molecular;Morphogenesis;notch protein;novel;Optics;Organ;Organoids;outreach;pandemic disease;Participant;Pathway interactions;Postdoctoral Fellow;posters;Process;programs;Property;regenerative biology;Research;Research Personnel;Science;Scientist;self organization;Societies;Spain;stem cells;Student Selections;student training;Students;symposium;synergism;System;Technology;Time;Tissues;tool;training opportunity;Update;Variant;Woman

PROJECT_TITLE: 11th Latin American Society for Developmental Biology (LASDB) Conference

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Developmental Biology Study Section[CHHD-C]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: SAN FRANCISCO

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Commensal bacteria critically support skin immune homeostasis, and breakdown of this symbiosis contributes to common chronic inflammatory skin disorders. Greater mechanistic understanding of these processes will lay the groundwork for future therapeutic strategies targeting host-commensal interactions in skin. The proposed translationally oriented studies use innovative approaches to define the role of a specific cell type, type 2 conventional dendritic cells, in cutaneous immune regulation and elucidate the bacterial molecules and host pathways influencing their behavior.

PI_NAMEs: SCHARSCHMIDT, TIFFANY CRAWFORD (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Acne;Animal Model;Antigen-Presenting Cells;Antigens;Atopic Dermatitis;Bacteria;Behavior;Biopsy;CD4 Positive T Lymphocytes;Cell Communication;Cell Physiology;cell type;Cells;Cellular biology;chronic inflammatory skin;commensal bacteria;commensal microbes;Cues;Cutaneous;Data;Dendritic Cells;Detection;dimensional analysis;Disease;Dissection;Engineered skin;Functional disorder;Future;germ free condition;Gnotobiotic;Goals;Hidradenitis Suppurativa;high dimensionality;Homeostasis;Human;human tissue;Immune;Immune Tolerance;immunoregulation;Inflammatory;innate immune pathways;innovation;Left;Ligands;Maintenance;Measures;Mediating;Microbe;microbial community;microbiome;microbiota;mouse model;Mus;mutant;Myeloid Cells;Nature;Neonatal;novel;novel therapeutic intervention;Pathologic;Pathway interactions;Phagocytosis;Phenotype;Population;Positioning Attribute;prevent;Process;receptor;receptor binding;Regulatory T-Lymphocyte;response;Role;Shapes;Signal Transduction;single cell analysis;Site;Skin;skin disorder;skin microbiome;Surface;Symbiosis;System;T-Lymphocyte;Testing;Therapeutic;Tissues;TLR2 gene;tool;Transgenic Animals;Transgenic Mice;uptake;Work

PROJECT_TITLE: Functional Dissection of Regulatory Myeloid Cells in Microbe-Immune Crosstalk in Skin


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;HIV/AIDS;Health Services;Infectious Diseases;Mental Health;Pediatric;Pediatric - AIDS;Prevention

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative Achieving the UNIADS 95-95-95 target by 2030 in South Africa has the potential to avert over 1.2 million deaths but will require innovative solutions to target those who are not served by the current healthcare system. Working with The University of Cape Town and The City of Cape Town Department of Health, we will comprehensively assess the effectiveness, mechanisms of effect, and implementation outcomes of our proposed person-centered model of care to provide insights that can be used to increase its public health impact. This research has the potential to change clinical practice in South Africa and throughout Southern Africa, where innovative approaches to managing disengagement are urgently needed.

PI_NAMEs: KATZ, INGRID T. (contact);ORRELL, CATHERINE ;SABIN, LORA L

PROGRAM_OFFICER_NAME: GREENWOOD, GREGORY LOUIS

PROJECT_TERMS: Address;Adherence;AIDS prevention;antiretroviral therapy;Back;barrier to care;Behavior;Behavioral Mechanisms;care costs;care outcomes;Caring;Cessation of life;Cities;Clinic;clinical practice;Collaborations;Continuity of Patient Care;Counseling;Data;design;Disclosure;effective therapy;Effectiveness;effectiveness evaluation;efficacy evaluation;Enrollment;Ensure;Epidemic;epidemic response;evidence base;experience;Face;flexibility;Fright;Future;Goals;Guidelines;Health;health data;Health Promotion;Healthcare Systems;high risk;HIV;hybrid type 1 trial;Hybrids;implementation outcomes;improved;Individual;innovation;insight;interest;Interruption;Intervention;Link;Mental disorders;Methods;Modeling;mortality;Motivation;Outcome;Participant;Patient Compliance;peer;person centered;Personal Satisfaction;Persons;Pharmaceutical Preparations;Pharmacy facility;Policies;prevent;Prevention;primary outcome;Process;Proctor framework;Professional counselor;Provider;Province;Public Health;Randomized;Randomized, Controlled Trials;recruit;Regimen;Research;response;routine care;scale up;secondary outcome;Self Management;Service delivery model;Services;Site;social;social stigma;Social support;South Africa;South African;Southern Africa;standard of care;substance use;success;Sustainable Development;System;Tenofovir;Testing;therapy adherence;transmission process;treatment adherence;trial design;Universities;Urine;Viral;Viral Load result;Wait Time;Work

PROJECT_TITLE: The SUSTAIN 2 study - SUStained HIV Treatment for Adherence After Interruption in Care

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CCHI-K (02)]


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative In sepsis, a multi-organ disease, the study of circulating proteins and metabolites in blood may enable relevant, comprehensive profiling. Compared to plasma, whole blood is easier to obtain, may exhibit less processing– driven variability, and allows for the analysis of tractable erythrocyte-specific biology. The application will focus on the development and validation of methods for proteomic and metabolomic analysis of dried blood and their eventual broad deployment in sepsis biorepositories.

PI_NAMEs: FOSTER, MATTHEW WOLF (contact);MCMAHON, TIMOTHY J

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Adoption;Affect;Ambulatory Care Facilities;Antibiotics;biobank;Biological Assay;Biology;Blood;Blood specimen;C-reactive protein;Cause of Death;cell type;Cells;Cessation of life;Clinical;Clinical Data;Clinical Management;Code;cohort;Collecting Cell;Collection;cost;Coupled;COVID-19;Critical Illness;Data;data integration;data repository;Data Set;Death Rate;demographics;Development;Devices;Disease;Dryness;Electronic Health Record;Erythrocytes;Exhibits;Functional disorder;Future;Generations;glycosylation;Goals;high throughput screening;Hospitals;Immune response;Immune signaling;In Vitro;Infection;Intensive Care Units;IV Fluid;Laboratories;Life;Liquid Chromatography;Long-Term Effects;Mass Spectrum Analysis;Metabolism;metabolome;metabolomics;Methodology;Methods;Morbidity - disease rate;mortality;multidisciplinary;Multiomic Data;multiple omics;novel;Organ;Outcome;Pathway Analysis;Pathway interactions;Patient Care;Patient Selection;Patients;Persons;Phase;Phenotype;Phosphorylation;Pilot Projects;Plasma;post-COVID-19;Post-Translational Protein Processing;Preparation;procalcitonin;Procedures;protein profiling;Proteins;Proteome;Proteomics;Pythons;Quality Control;Recovery;Reporting;Role;Sampling;Sepsis;septic patients;Serum;severe COVID-19;Shipping;Signal Pathway;Signal Transduction;stability testing;standard of care;Standardization;tandem mass spectrometry;Techniques;Tissues;translational approach;translational scientist;Translations;Universities;Validation;Viremia;Whole Blood;Work

PROJECT_TITLE: Multiomic, mass spectrometry-based analysis of dried blood for deep phenotyping of sepsis

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


NIH_SPENDING_CATS: Clinical Research;Emergency Care;Hematology;Infectious Diseases;Pediatric;Precision Medicine;Sepsis

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: PROJECT NARRATIVE Sepsis is broadly defined as life-threatening organ dysfunction caused by infection, however, the experience of sepsis varies widely between individuals and within individuals, which makes both diagnosis and treatment challenging. We propose testing the feasibility of new approaches to collect, process, and analyze biologic data from blood specimens very early in the sepsis course and link this information to granular clinical data from the electronic health record. We believe we can use these data to characterize some of the complexity of sepsis with the long-term goal of enabling precision medicine approaches to diagnosing and treating this life- threatening condition.

PI_NAMEs: BALAMUTH, FRANCES B (contact);SANCHEZ-PINTO, LAZARO NELSON

PROJECT_TERMS: Accident and Emergency department;Adult;Age;Apoptosis;Applied Research;Bioenergetics;Biological;Biological Assay;Biological Specimen database;Biology;biomarker panel;Blood Plasma Volume;Blood specimen;Cessation of life;Characteristics;Child;Clinical;Clinical Data;clinical database;clinical phenotype;Clinical Research;cohort;comorbidity;Complex;Critical Care;Critical Illness;cytokine;Data;Data Collection;data pipeline;data registry;Data Science;Death Rate;design;Development;Diagnosis;Disease;Electronic Health Record;Emergency Care;Emergency Medicine;Enrollment;Evaluation;exhaustion;experience;feasibility testing;Flow Cytometry;Functional disorder;Funding;Future;Glean;Goals;high dimensionality;high risk;Hour;Hypoxemia;Individual;individual variation;Infection;Inflammatory;innovation;Life;Link;Liquid substance;Lymphocyte Activation;Lymphocyte Function;lymphocyte proliferation;Medical;Metabolic;metabolomics;Morbidity - disease rate;multidisciplinary;Multiple Organ Failure;new therapeutic target;novel strategies;Organ;Outcome;participant enrollment;pathogen;Patients;Pattern;pediatric emergency;pediatric sepsis;Pharmaceutical Preparations;Phase;Phenotype;phenotypic data;Pilot Projects;Plasma;precision medicine;Process;Production;prospective;Proteomics;Quality-Adjusted Life Years;Registries;Research;Research Infrastructure;Research Personnel;response;Resuscitation;Risk;sample collection;Sampling;Sepsis;Shock;Site;Specimen;Surface;targeted treatment;Techniques;Testing;Thrombocytopenia;Time;translational immunology

PROJECT_TITLE: Pediatric Sepsis Biorepository and Clinical Database

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-N(90)]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

ORG_CITY: BERKELEY

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative A more complete understanding of the complex microbial communities that inhabit the human body is needed in order to develop new strategies to manipulate these communities for beneficial health outcomes. This research addresses this need by examining the vitamin B12 family of essential metabolites that are shared among bacteria and can influence microbial community structure.

PI_NAMEs: TAGA, MICHIKO E. (contact)

PROGRAM_OFFICER_NAME: KEANE-MYERS, ANDREA

PROJECT_TERMS: Address;Amino Acids;Automobile Driving;Bacteria;Biochemical Pathway;Biochemistry;Bioinformatics;bioinformatics pipeline;Cobalt;Coenzymes;cofactor;Communities;Complex;Corrinoids;design;Development;Environment;Enzymes;Family;Foundations;Funding;Genes;Genetic;genetic approach;Genome;Goals;Health;Human;Human body;human model;Metabolic;Metabolism;Methods;microbial community;Microbiology;microorganism interaction;Modeling;Molecular;National Institute of General Medical Sciences;nucleobase;Outcome;Planet Earth;predictive signature;preference;programs;Reaction;Research;Sampling;Specificity;Structure;System;Testing;Vitamin B 12;Work

PROJECT_TITLE: Bacterial Corrinoid Metabolism Across Scales: From Molecular Specificity to Community Dynamics

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


NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Women's Health Research

ORG_CITY: TOLEDO

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS

PHR: Cancer stemness in triple-negative breast cancer (TNBC) disproportionately affects African American (AA) than European White (EW) women that leads to aggressive primary tumor progression and metastasis leading to many fatalities in AA women. Altered tumor protein profile in AA-TNBC may contribute to such a differential clinical outcome. The supplement proposal outlines a strategy to obtain preliminary data that will point to a disproportionate role played by the mRNA helicase, eIF4A1 in supporting cancer stemness program in AA-TNBC than EW-TNBC tumors.

PI_NAMEs: RAMAN, DAYANIDHI  (contact);SHARMA, DIPALI

PROGRAM_OFFICER_NAME: O'HAYRE, MORGAN

PROJECT_TERMS: ABCB1 gene;ABCG2 gene;Address;Adjuvant Chemotherapy;Affect;African American;African American Women;aldehyde dehydrogenases;Apoptosis;ATP-Binding Cassette Transporters;Bioinformatics;Breast Cancer Cell;Breast Cancer Model;Breast Cancer Patient;c-myc Genes;cancer health disparity;carcinogenesis;CD44 gene;Cells;Chemoresistance;Clinical;comparative;Cyclin D1;cyclin D3;Data;Data Set;Disease;Disparity;Distant Metastasis;docetaxel;Drug resistance;efficacy evaluation;Eukaryotic Initiation Factors;European;FDA approved;feeding;Future;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Genetic;Goals;Grant;helicase;Hispanic;Hispanic Women;Human;immunodeficiency;immunodeficient mouse model;immunoregulation;Immunotherapy;In complete remission;In Vitro;Invaded;Isoenzymes;Malignant Breast Neoplasm;Malignant Neoplasms;MCL1 gene;Mediating;Messenger RNA;Modality;mortality;mouse model;mRNA Translation;Mus;Nature;Neoadjuvant Therapy;Neoplasm Metastasis;neoplastic cell;Oncogenic;Outcome;Parents;Pathologic;patient derived xenograft model;Patient-derived xenograft models of breast cancer;Patients;Pharmaceutical Preparations;pharmacologic;Play;pluripotency;Poly(ADP-ribose) Polymerase Inhibitor;Population;prevent;Primary Neoplasm;programs;Proliferating;Property;Protein Isoforms;Proteins;Publishing;Radio;Recurrence;Regulation;Relapse;Resistance;Resistance development;Rho-associated kinase;RNA analysis;Role;self-renewal;stem-like cell;stemness;Stromal Cells;Structure;Survival Analysis;survivin;targeted treatment;Therapeutic;trait;transcription factor;transcriptome sequencing;transdifferentiation;Treatment Failure;triple-negative invasive breast carcinoma;tumor;Tumor Burden;tumor initiation;tumor progression;tumorigenic;White Women;Woman

PROJECT_TITLE: Targeting eIF4A1 in drug-resistant breast cancer stem-like cells

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Bioengineering;Genetics

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: RICE UNIVERSITY

PHR: Every time cells divide; their DNA is damaged at a low level. This “endogenous” DNA damage is an important factor in normal and aberrant animal development, but because it happens at a low level over long time periods it hasn’t been possible to study in detail. I propose to develop a new tool with the resolving power to study endogenous DNA damage and other rare cellular processes over weeks to months in developing mammals.

PI_NAMEs: LOVELESS, THERESA BERENS (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Affect;Animals;Architecture;Biological;cancer cell;Cell Cycle;Cell Physiology;Cells;Characteristics;Cisplatin;Collection;Cultured Cells;Development;DNA;DNA Damage;DNA damage checkpoint;Dose;Engineering;Event;experience;experimental study;Genes;genetically modified cells;Genome;Genome Stability;genomic locus;Head and Neck Cancer;in vivo;Insertion Mutation;interest;Lead;Life;Long-Term Effects;Longitudinal Studies;Malignant Neoplasms;Mammals;Molecular;Monitor;Mouse Embryonic Stem Cells;mouse model;Mutation;new technology;novel strategies;Nucleotides;Optics;parent grant;patient derived xenograft model;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phenotype;Physiological;Population;promoter;Proteins;Recording of previous events;Records;Resistance;response;RNA;Role;Sampling;Signal Transduction;single-cell RNA sequencing;Techniques;Technology;Testing;Therapeutic;Time;tissue culture;tool;triple-negative invasive breast carcinoma;Work;Writing;Xenograft Model

PROJECT_TITLE: Diversity Supplement: Deep cell history tracking: engineering cells that write their detailed life stories into their DNA to study DNA damage

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE: Cancer-associated fibroblasts (CAFs) plan an essential role in the tumor microenvironment for numerous tumor types and may be important in the development of aggressive thyroid cancers such as anaplastic thyroid carcinomas (ATCs). In this proposal, we will study the role of CAFs, as well as their paracrine Wnt signaling, in ATCs using single-cell sequencing, spatial transcriptomics, novel thyroid cancer organoids with corresponding CAF cultures, and a patient-derived xenograft mouse model to discover potential new therapy for anaplastic thyroid carcinoma.

PI_NAMEs: WEISS, VIVIAN LEE (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: Affect;African American;Age;anaplastic thyroid cancer;Architecture;Biological;Biological Factors;BRAF gene;cancer health disparity;Cancer Patient;cancer type;Cells;Cellularity;Classification;cohort;Cohort Studies;Collaborations;Communities;community-level factor;Comparative Study;Complex;Data;Databases;Development;Disease Progression;Evaluation;Fibroblasts;Follicular thyroid carcinoma;Funding;Future;Genetic;Genomics;health care disparity;high risk;Histologic;Immunofluorescence Immunologic;improved;improved outcome;Individual;Infiltration;Ligands;Malignant neoplasm of prostate;Malignant neoplasm of thyroid;Malignant Neoplasms;Molecular Profiling;mouse model;mutant;Mutation;neoplastic cell;novel;novel therapeutics;Organoids;Outcome;outcome disparities;Papillary thyroid carcinoma;paracrine;Parents;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pattern;Phenotype;predictive signature;prognostic signature;Publications;Publishing;recruit;Research;Research Personnel;Role;sex;single cell sequencing;single-cell RNA sequencing;social factors;sociocultural determinant;sociodemographic factors;sociodemographics;Socioeconomic Factors;Socioeconomic Status;Study models;Testing;Thyroid carcinoma;thyroid neoplasm;transcriptomics;tumor;tumor behavior;tumor microenvironment;Tumor Promotion;WNT Signaling Pathway

PROJECT_TITLE: The Role of Cancer-Associated Fibroblasts in Thyroid Carcinoma

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Asthma;Climate-Related Exposures and Conditions;Lung

ORG_CITY: RALEIGH

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: NORTH CAROLINA STATE UNIVERSITY RALEIGH

PHR: PROJECT NARRATIVE Nearly one-third of the United States population lives in areas with unhealthy levels of ambient ozone, causing respiratory problems in children, elderly, and patients with pre-existing cardiopulmonary diseases. Ozone results in predominantly Type 2 (Th2) inflammatory responses including eosinophilic inflammation and mucous cell metaplasia that are also the hallmarks of allergic asthma. Using innovative approaches, supported by our novel and exciting data, we will attempt identification of a key cell-type(s) involved in the pathogenic manifestation of ozone-induced Th2 inflammation and thus, amenable for targeting of Th2 pathways in ozone- induced airway diseases.

PI_NAMEs: SAINI, YOGESH  (contact)

PROGRAM_OFFICER_NAME: NADADUR, SRIKANTH

PROJECT_TERMS: Ablation;Adoptive Transfer;Adult;age related;aged;Airway Disease;Allergens;Area;Asthma;Binding;Bronchoalveolar Lavage;cell type;Cells;Child;Clinical Trials;Complex;Data;Dendritic Cells;Development;Disease;Effector Cell;Elderly;eosinophil;eosinophilic inflammation;Exposure to;Extrinsic asthma;Functional disorder;Gender;granulocyte;IL-13Ralpha1;IL4 gene;IL4R gene;Inflammation;Inflammation Mediators;Inflammatory Response;inhibitor;innovation;Interleukin 4 Receptor;Interleukin-13;Knowledge;Liquid substance;LoxP-flanked allele;Lung;lung injury;Macrophage;Mediating;Mediator;Metaplasia;Modeling;Molecular;mouse model;Mouse Strains;Mucous body substance;Muramidase;Mus;Myelogenous;Myeloid Cells;neonate;neutrophil;novel;Outcome;Ozone;ozone exposure;Pathogenicity;Pathologic;Pathway interactions;Patients;Population;Production;Pulmonary Heart Disease;receptor;recruit;respiratory;response;Role;Signal Transduction;Testing;Therapeutic;therapeutically effective;United States;Vesicle;women versus men

PROJECT_TITLE: Understanding the role of myeloid cells in ozone-induced airway disease


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Schizophrenia;Serious Mental Illness

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: Project Narrative  Schizophrenia poses a great social and economic burden in a significant percentage of patients, including increased risk for unemployment, homelessness, incarceration, chronic disability, and reduced life expectancy. This disability is thought to be closely related to cognitive deficits in patients. By seeking to better understand the neural basis of these deficits, this application seeks to identify new brain mechanisms that may be targeted by future treatments in order to improve outcomes in this patient group.

PI_NAMEs: VAN SNELLENBERG, JARED XAVIER (contact)

PROGRAM_OFFICER_NAME: WOUHIB, ABERA

PROJECT_TERMS: Area;Attention;attentional control;behavior test;Behavioral;Biological Assay;biomarker identification;biotypes;Brain;Brain region;case control;Chronic disability;Clinical Trials;Cognition;Cognitive;cognitive ability;Cognitive deficits;cognitive neuroscience;cognitive process;cognitive task;Collection;convolutional neural network;Data;Data Set;disability;Economic Burden;effective therapy;Equation;Exhibits;flexibility;Functional disorder;Functional Magnetic Resonance Imaging;functional MRI scan;functional outcomes;Future;Goals;Homelessness;imaging study;Impairment;Imprisonment;improved;improved outcome;Individual;interest;Life Expectancy;Link;Literature;long term memory;Maintenance;Maps;Memory;Memory impairment;memory retrieval;Modeling;Motivation;National Institute of Mental Health;neural;neural circuit;neural correlate;neural network;Neural Network Simulation;Outcome;Participant;Pathogenesis;patient subsets;Patients;Pattern;Performance;potential biomarker;Process;Psychiatric Diagnosis;Psychiatry;psychotic symptoms;Recommendation;repetitive transcranial magnetic stimulation;Reporting;Research;Research Domain Criteria;Research Personnel;Risk;Role;Sampling;Schizophrenia;Short-Term Memory;social;Specific qualifier value;Structure;Symptoms;Task Performances;Techniques;Testing;treatment research;Unemployment;Update;Work

PROJECT_TITLE: A data-driven reconceptualization of the RDoC construct of working memory: Neural correlates of underlying factors and implications for schizophrenia

STUDY_SECTION: APDA

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


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Complementary and Integrative Health;Dietary Supplements;Natural Products;Nutrition

ORG_CITY: PISCATAWAY

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: This renewal project will enable Tajikistan and Indonesia to provide the in-country research training on botanicals for prevention and treatment of chronic diseases, such as diabetes, rheumatoid and osteoarthritis and digestive and neurological disorders. Extensive online and face-to-face training curriculum will be coordinated by the Center for Botanicals and Chronic Diseases (CBCD). CBCD will train 10 scientists in Tajikistan and 24 scientists in Indonesia, thus contributing to improved public health and medical research in both countries.

PI_NAMEs: RASKIN, ILYA  (contact)

PROGRAM_OFFICER_NAME: LEVINTOVA, MARYA

PROJECT_TERMS: Biodiversity;Biomedical Research;Botanicals;Cardiovascular Diseases;Cementation;Central Asia;Chronic Disease;Collaborations;combat;common treatment;community college;Community Outreach;Country;Degree requirements;Diabetes Mellitus;Distance Learning;doctoral student;Educational Curriculum;Educational workshop;Ensure;Event;evidence base;experience;Faculty;Foundations;Funding;Grant;Health;Health Professional;Indonesia;Inflammation;Institution;Interdisciplinary Study;International;Intestinal Diseases;Laboratories;Louisiana;Mentors;Metabolic;Metabolic syndrome;Minority-Serving Institution;Monitor;Nervous System Disorder;online course;Pharmacologic Substance;Postdoctoral Fellow;Prevention;programs;Research Training;resilience;Resources;Rheumatoid Arthritis;Scientist;Students;symposium;synergism;Tajikistan;Teacher Professional Development;Testing;Training;Training and Infrastructure;Training Programs;United States National Institutes of Health;Universities;Visit

PROJECT_TITLE: Research Training Center for Botanicals and Chronic Diseases in Tajikistan and Indonesia


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Substance Misuse;Underage Drinking

ORG_CITY: CHAPEL HILL

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE Adolescent binge drinking has long-term consequences on brain function which are only beginning to be understood. These proposed experiments will characterize the impact of adolescent alcohol exposure on the ability of newborn neurons to integrate into brain circuitry and contribute to cognitive impairments in adulthood. By elucidating the mechanisms underlying the long-term impacts of alcohol on the adolescent brain, this research will provide critical insight into potential therapeutic targets by which to reverse alcohol’s developmental effects on the brain and behavior.

PI_NAMEs: MACHT, VICTORIA ALICE (contact)

PROGRAM_OFFICER_NAME: LIU, QI-YING

PROJECT_TERMS: Abstinence;Address;Adolescence;Adolescent;adolescent alcohol exposure;adolescent binge drinking;Adult;adult neurogenesis;alcohol exposure;Alcohols;antagonist;Anti-Inflammatory Agents;Astrocytes;Automobile Driving;Behavior;Behavioral;Birth;Brain;brain circuitry;CCL2 gene;Cell Proliferation;Cells;Child Care;Cholinesterase Inhibitors;Cognitive;Data;Deoxyuridine;Development;Electrophysiology (science);Ethanol;Euthanasia;experimental study;Female;flexibility;FOS gene;Functional impairment;Future;Galantamine;Gene Expression;Glial Fibrillary Acidic Protein;Glycyrrhizic Acid;Grant;Hippocampus;Histologic;HMGB1 gene;Immediate-Early Genes;Immunofluorescence Immunologic;Impaired cognition;Impairment;Indomethacin;Inflammatory;inflammatory marker;insight;intraperitoneal;Knowledge;Label;life span;Link;male;Maps;Mediating;Memory;memory recognition;Microglia;morris water maze;Mus;N-Methylaspartate;nerve stem cell;neural circuit;neurogenesis;Neuroimmune;neuroinflammation;Neuronal Differentiation;neuronal excitability;Neuronal Plasticity;neuronal survival;Neurons;Newborn Infant;newborn neuron;novel;object recognition;optogenetics;p65;parent grant;Performance;pharmacologic;Phenotype;Phosphodiesterase Inhibitors;Physiological;Population;postnatal;postsynaptic;Predisposition;programs;Property;PTGS2 gene;Regulation;Reporter;Research;Research Training;response;restoration;Reversal Learning;sex;Signal Transduction;social stress;Son;Stress;Tamoxifen;Techniques;Testing;therapeutic target;TLR4 gene;tool;Training;Transgenic Mice;Transgenic Organisms;Trees;Tube

PROJECT_TITLE: Supplement: Adolescent intermittent ethanol induction of neuroimmune signaling disrupts the mature phenotype of surviving hippocampal neuroprogenitors


NIH_SPENDING_CATS: Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: PROVIDENCE

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE This study tracks the trajectories of neighborhood change segregating Blacks from whites for a large sample of cities and metropolitan areas from the early 20th Century through 2020. It will compare changes that were dominated by white flight and minority invasion/succession in the 1930s and 1940s to the postwar period when segregation stemmed increasingly from the exclusion of Blacks from fast-growing suburbs, and recent decades when segregation has begun to decline. The harmonized neighborhood data base developed for this analysis will be made publicly available, supporting a much wider range of studies of urban change.

PI_NAMEs: LOGAN, JOHN R (contact)

PROGRAM_OFFICER_NAME: CHINN, JUANITA JEANNE

PROJECT_TERMS: Area;Attention;Black Populations;Black race;Categories;Caucasians;Central City;Chicago;Cities;Data;data harmonization;data infrastructure;data resource;Data Set;Databases;Development;Disparity;Documentation;Education;Employment Opportunities;Ethnic Population;Exclusion;experience;Foundations;Future;Geography;Ghetto;Health;Hispanic Populations;improved;Income;Individual;Institution;Invaded;Life;Longitudinal Studies;Maps;Measurement;Measures;Methods;metropolitan;Minority;Modeling;Neighborhoods;Outcome;Pathway interactions;Pattern;Phase;Population;Procedures;Process;Race;racial diversity;racial population;Racial Segregation;rapid growth;Research;Research Personnel;residential segregation;Resources;Sampling;segregation;Social Class;Social Mobility;Source;stem;suburb;success;Time;trend;urban area;Urban Renewal;violence exposure;War;World War II

PROJECT_TITLE: Improving Measurement and Documentation of Long-term Neighborhood Change and Racial Segregation

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: PORTLAND

ORG_DEPT: NEUROSCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Mechanotransduction, the conversion of physiological force into biological signals, is crucial for many physiological processes such as touch or pain sensation, blood pressure regulation, and muscle contraction. The importance of mechanotransduction is underscored by its role in disorders such as chronic pain, atherosclerosis, and muscular dystrophies. Mechanotransduction is driven by ion channels activated when force is applied to cell membranes, but the lack of a highly precise method for MA channel activation in vitro has hampered progress in the field. This proposal uses an innovative and tractable technique to activate and assay MA ion channels that will enable their deep biophysical and pharmacological characterization, which will be vital to probe their in vivo consequences.

PI_NAMEs: MURTHY, SWETHA  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Atherosclerosis;azobenzene;Biological;Biological Assay;Biophysics;Blood flow;blood pressure regulation;Calcium;Cell membrane;Cells;chronic pain;cis trans isomerization;Disease;Ear;Electrophysiology (science);Environment;Event;Family;Feathers;Glass;Hearing;Human;Image;In Vitro;in vivo;innovation;Ion Channel;Light;Lipids;Measurement;mechanical force;Mechanical Stimulation;Mechanics;mechanotransduction;Membrane;Methods;Molecular;Muscle Contraction;Muscular Dystrophies;novel;novel strategies;Optics;Organelles;pain sensation;Pathologic;pharmacologic;Pharmacology Study;Physiological;Physiological Processes;pressure;Process;Property;Proteins;Role;Signal Transduction;Skin;sound;Stimulus;Stretching;Techniques;Tissues;Touch sensation;vibration;Work

PROJECT_TITLE: A New Approach to Study Mechanically Activated Ion Channels


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Dental, Oral, and Craniofacial Disease;Pain Research;Temporomandibular Muscle/Joint Disorder (TMJD)

ORG_DEPT: ORTHOPEDICS

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: Project Narrative Temporomandibular joint disorders (TMJDs) are a set of complex, poorly understood painful conditions that negatively affect many children and adults in the US. In this study, we will use single-cell RNA sequencing of TMJ synovial fluid to better understand these conditions and identify novel therapeutic options.

PI_NAMEs: DANG, HIEN T.;TAUB, DANIEL ;TOMLINSON, RYAN  (contact)

PROGRAM_OFFICER_NAME: WAN, JASON

PROJECT_TERMS: Adolescent;Adult;Affect;Age;Biological Assay;Biological Markers;biomarker identification;Blood;Blood specimen;Cancer Center;Caring;cell motility;Cells;Child;Classification;Clinic;Clinical;Clinical Protocols;Collaborations;Complex;Consent Forms;Data;data management;design;Development;Disease;Documentation;Eating;Enrollment;Ensure;evidence base;Flare;Gene Expression;Goals;Harvest;improved;Individual;Inflammatory;Informed Consent;Institutional Review Boards;Knowledge;Mental Health;Methods;Modality;Molecular Biology;National Institute of Dental and Craniofacial Research;new therapeutic target;novel therapeutic intervention;novel therapeutics;Occupations;Operative Surgical Procedures;oral surgery specialty;Oral Surgical Procedures;Pain;participant enrollment;Patients;Phase;Physicians;Population;Positioning Attribute;Process;Protocols documentation;Qualifying;Quality of life;recruit;Research;Research Personnel;Resolution;Rheumatoid Arthritis;RNA analysis;Sampling;Scientist;sex;Signal Pathway;Signal Transduction;single cell analysis;single cell sequencing;single-cell RNA sequencing;Symptoms;Synovial Fluid;Synovial Membrane;Technology;Temporomandibular Joint;Temporomandibular Joint Disorders;Testing;therapeutic target;volunteer;wasting;Waxes;Work

PROJECT_TITLE: Single cell analysis of healthy and diseased temporomandibular joint synovial fluid


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Cancer;Chronic Liver Disease and Cirrhosis;Clinical Research;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Hepatitis;Liver Cancer;Liver Disease;Microbiome;Nutrition;Obesity;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Hepatocellular carcinoma incidence has been increasing in the past several decades in the United States due to increasing prevalence of metabolic-dysfunction associated steatotic liver disease. Native Hawaiians and other Pacicific Islanders have high risk of metabolic-dysfunction associated steatic liver disease and hepatocellular carcinoma. The adminstrative supplement will investigate the different risk profiles for Native Hawaiians/other Pacific Islanders.

PI_NAMEs: BEHARI, JAIDEEP ;YUAN, JIAN-MIN  (contact)

PROGRAM_OFFICER_NAME: STARKS, VAURICE

PROJECT_TERMS: Address;Administrative Supplement;Adult;Affect;African American population;Age;Alcohols;American;Animal Model;Antigens;Applications Grants;Area;Asian Americans;bile acid metabolism;Bile Acids;Biochemical;Biological Factors;Biological Markers;cancer health disparity;cancer risk;Carcinogens;Cessation of life;Characteristics;Cirrhosis;Clostridium;cohort;Cohort Studies;Collaborations;cytokine;Data;data integration;Deoxycholic Acid;Development;Diabetes Mellitus;Diet Habits;Digestion;Disparity;Eligibility Determination;end stage liver disease;Enrollment;Ensure;Environmental Risk Factor;Ethnic Origin;experimental study;Exposure disparity;Exposure to;Family;Fatty acid glycerol esters;Fibrosis;follow-up;Genomics;genotoxicity;Glucose;Glycoconjugates;Growth and Development function;gut bacteria;gut dysbiosis;gut microbiome;gut microbiota;Hawaii;Hawaiian;Hawaiian population;Health;Healthcare Systems;Hepatic;Hepatocyte;high risk;high risk population;High-Risk Cancer;Homeostasis;Hormonal;Human;Immune;Immune Tolerance;Immunologic Surveillance;Immunomodulators;Incidence;Individual;Infection;Inflammation;Inflammatory;inter-institutional;Interleukin-12;interleukin-23;Interleukins;Intestines;Japanese American;Klebsiella pneumoniae;Latino Population;Life Style;lifestyle factors;Link;Lipids;Liver;Liver diseases;Liver Fibrosis;liver injury;liver transplantation;Malignant neoplasm of liver;Malignant Neoplasms;member;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic syndrome;Metabolism;metabolomics;microbial;mortality;multi-ethnic;Mus;Native Hawaiian;Native Hawaiian or Other Pacific Islander;non-alcoholic fatty liver;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;Not Hispanic or Latino;novel;Obesity;Organ;Outcome;overexpression;Pacific Islander;parent grant;Parents;Participant;pathogen;Patients;Pennsylvania;permissiveness;Population;Population Heterogeneity;Portal vein structure;Prevalence;Primary carcinoma of the liver cells;Process;Property;prospective;Protocols documentation;Race;racial difference;racial diversity;Reaction;receptor;recruit;Recycling;Reporting;Research;Risk;Risk Factors;Samoan;Serum;Signaling Molecule;subcutaneous;Survival Rate;T cell response;T-Lymphocyte;Toxic Environmental Substances;Triglycerides;tumor growth;Tumor Promotion;tumor-immune system interactions;United States;Variant;Visceral fat

PROJECT_TITLE: Differential risk factors for hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease (MASLD) patients of native Hawaiians compared with US whites

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Epilepsy;Eye Disease and Disorders of Vision;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Rare Diseases;Rett Syndrome;Women's Health Research

ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: Project Narrative - [From parent grant U01NS114312] Pathogenic variants in the Cyclin-dependent kinase like 5 (CDKL5) gene cause CDKL5 deficiency disorder (CDD, MIM 300672, 105830), a severe developmental and epileptic encephalopathy associated with cognitive and motor impairments and cortical visual impairment. While capability for disease modifying therapies is accelerating, there is a critical barrier for clinical trial readiness that may result in failure of these therapies, not due to lack of efficacy but due to lack of validated outcome measures and biomarkers. The measures and biomarkers validated here will be adaptable to other developmental and epileptic encephalopathies.

PI_NAMEs: BENKE, TIMOTHY A (contact);DOWNS, JENNY ;LEONARD, HELEN M;MARSH, ERIC D

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Acceleration;Address;Animal Model;Biological Markers;biomarker validation;CDKL5 disorder;cerebral visual impairment;Clinical;clinical outcome measures;clinical trial readiness;Clinical Trials;Cyclin-Dependent Kinases;Data;Development;Disease;Electroencephalography;Ensure;epileptic encephalopathies;Evoked Potentials;experience;gene therapy;Genes;Genetic;Goals;Impaired cognition;implementation evaluation;Measurement;Measures;Modification;motor disorder;motor impairment;Multi-Institutional Clinical Trial;National Institute of Neurological Disorders and Stroke;novel therapeutics;Outcome;Outcome Measure;parent grant;Pathogenicity;Population;Positioning Attribute;Reproducibility;Research;Rett Syndrome;Severities;Site;Symptoms;Testing;Therapeutic;tool;Treatment Failure;Validation;Variant;Work

PROJECT_TITLE: Multi-site validation of biomarkers and core clinical outcome measures for clinical trial readiness in CDKL5 Deficiency Disorder


ADMINISTERING_IC: CE

IC_NAME: NATIONAL CENTER FOR INJURY PREVENTION AND CONTROL

PHR: Outcomes after pediatric concussion or mild traumatic brain injury (mTBI) can be improved with access to appropriate care. This project seeks to improve outcomes and reduce disparities via implementation of the CDC Pediatric mTBI Guideline using electronic clinical decision support, mobile health and telehealth interventions.

PI_NAMEs: ARBOGAST, KRISTY  (contact);MASTER, CHRISTINA L.

PROJECT_TITLE: CE22-007, Improving outcomes and reducing disparities through integrated primary care-specialty care implementation of the CDC Pediatric Mild TBI Guideline


ADMINISTERING_IC: OH

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_CITY: MARSHFIELD

ORG_NAME: MARSHFIELD CLINIC RESEARCH FOUNDATION

ORG_STATE: WI

PI_NAMEs: SWENSON, ANDREA  (contact)

PROJECT_TITLE: National Center of Excellence for the Prevention of Childhood Agricultural Injury - 2020


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: CORAL GABLES

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF MIAMI CORAL GABLES

ORG_STATE: FL

PHR: Project Narrative Black women living with HIV (BWLWH; 40% unsuppressed) are marginalized and understudied, in the U.S. in general and in Miami, FL, a southern HIV epicenter. Our 1-year R56, occurring during the time of heighten visibility on racism in the U.S. and COVID-19, has further demonstrated the importance of longitudinally studying the unique role of microaggressions and frequent adversities (e.g. violence/trauma) in relation to HIV viral suppression among BWLWH. Our proposed study will allow for continued longitudinal data collection, and directly generate community-informed interventions to improve viral suppression among BWLWH; thereby helping us to move closer to Zero Infections, Zero Discrimination, and Zero AIDS-Related Deaths.

PI_NAMEs: DALE, SANNISHA K. (contact)

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adherence;Behavior;Black Populations;Black race;black women;Buffers;Caring;Cessation of life;Climate;Communities;community engaged intervention;community engagement;community partners;COVID-19;Data;Data Collection;Data Sources;Diagnosis;Discrimination;Domestic Violence;Ecological momentary assessment;Employment;Enrollment;Epidemic;experience;Female;Florida;Frequencies;Funding;Future;Grant;Hair;Health;Health behavior;HIV;HIV Seronegativity;HIV/AIDS;Housing;improved;Individual;Infection;information gathering;innovation;Intervention;intimate partner violence;Investigation;Lesbian Gay Bisexual Transgender Queer;Literature;Longitudinal Studies;marginalization;marginalized population;Measures;Mediating;medication compliance;Mental Depression;Mental Health;Methodology;microaggression;Modeling;Monitor;National Institute of Mental Health;Nature;neglect;Neighborhood Health Center;Neighborhoods;Outcome;Pathway interactions;Persons;physical assault;Population;Post-Traumatic Stress Disorders;Posttraumatic growth;Poverty;Published Comment;Race;racism;recruit;Reduce health disparities;Research;Research Priority;Research Support;resilience;resilience factor;Resources;response;Role;Self Efficacy;sexual assault;Shapes;Shelter facility;social structure;Social support;Spirituality;stressor;Stroke;substance use;success;Symptoms;Testing;Text Messaging;therapy development;Time;Trauma;trauma symptom;treatment disparity;Treatment outcome;United States National Institutes of Health;Violence;Viral;Visit;Voice;White Women;Woman;Women's Group;Women's study;Work

PROJECT_TITLE: Monitoring Microaggressions and Adversities to Generate Interventions for Change (MMAGIC) for Black Women Living with HIV

STUDY_SECTION: HIBI

STUDY_SECTION_NAME: HIV/AIDS Intra- and Inter-personal Determinants and Behavioral Interventions Study Section[HIBI]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biodefense and Related Countermeasures;Brain Disorders;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Infectious Diseases;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Neurosciences;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Prevention;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: The results of the proposed study will begin to elucidate the link between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposure, central and peripheral inflammation in pregnancy, and psychiatric and cognitive sequelae postpartum. We will identify central and peripheral markers of subacute and long-term neuropsychiatric sequelae of SARS- CoV-2. The results of this study will have important implications for mental health in the vulnerable periods of pregnancy and postpartum, and will identify targets for personalized treatment to ameliorate long-term neuropsychiatric sequelae of Coronavirus Disease-19 (COVID-19) and other infections.

PI_NAMEs: DE WITTE, LOTJE DOROTHEE;PEREZ RODRIGUEZ, MARIA DE LAS MERCEDES  (contact)

PROGRAM_OFFICER_NAME: LAWHORN, COLLENE

PROJECT_TERMS: 2019-nCoV;Acute;Age;Antibodies;Attention;Autoantibodies;Autoimmune Process;Blood;Blood specimen;Central Nervous System;Cerebrospinal Fluid;Cognition;Cognitive;Cognitive deficits;cognitive performance;cognitive testing;cohort;Cohort Studies;COVID-19;COVID-19 sequelae;Data;Development;Diagnostic;Dimensions;Exclusion;executive function;Exposure to;fetal;Funding;General Population;Generations;Goals;high risk;Immunoassay;Immunoglobulin G;Impaired cognition;Infection;Inflammation;Inflammatory;inflammatory marker;Link;long term consequences of COVID-19;Long-Term Effects;Longitudinal Studies;Measures;Mediating;Mediator;Memory;Mental Health;Neurons;neuropsychiatric sequelae of COVID-19;neuropsychiatric symptom;neuropsychiatry;New York;Nucleocapsid;Outcome;pathogen;Performance;Peripheral;personalized medicine;Phenotype;post SARS-CoV-2 infection;Postpartum Depression;postpartum outcome;Postpartum Period;Postpartum Women;Pregnancy;Pregnant Women;Process;psychiatric symptom;reproductive;Risk Factors;Role;Sampling;SARS-CoV-2 antibody;SARS-CoV-2 exposure;SARS-CoV-2 infection;Vaccination;Vulnerable Populations;Woman

PROJECT_TITLE: Cerebrospinal fluid (CSF) and peripheral markers of the neuropsychiatric sequelae of COVID-19: The Generation C-SF pregnancy study

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Conditions Affecting the Embryonic and Fetal Periods;Health Services;Infant Mortality;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

ORG_CITY: GALVESTON

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

PHR: NARRATIVE Investigations by the MFMU Network focus on problems in clinical obstetrics, particularly those related to prevention of low birth weight, prematurity, and medical problems of pregnancy. These complications can lead to health problems at birth as well as later in life; therefore, research that may lead to their prevention has powerful potential for improving individual lives and public health.

PI_NAMEs: PACHECO, LUIS D (contact)

PROGRAM_OFFICER_NAME: CHAKHTOURA, NAHIDA ABDO

PROJECT_TERMS: Address;Admission activity;Ambulatory Care Facilities;antenatal;Area;Authorization documentation;Basic Science;Beds;Birth;Board Certification;Caring;Clinic;Clinical;clinical infrastructure;clinical investigation;clinical practice;Clinical Services;Clinical Trials;Collaborations;Computerized Medical Record;Consent;Contracts;Core Facility;Critical Care;Data;Data Analyses;Data Collection;data quality;Dedications;Department chair;design;Development;Diagnostic;Discipline of obstetrics;Documentation;electronic medical record system;Eligibility Determination;Employee;Enrollment;ethnic diversity;Ethnic Origin;Evidence based practice;experience;Faculty;fetal;follow-up;Funding;Genetic;Genomics;Goals;Health;Hepatitis C virus;high risk;Home;Hospitals;Human Resources;improved;Individual;Information Systems;Informed Consent;Infrastructure;innovation;Institution;intrapartum;Investigation;Laboratories;Leadership;Letters;Life;Link;Logistics;Low Birth Weight Infant;Manuscripts;Maternal and Child Health;Maternal-fetal medicine;Maternal-Fetal Medicine Units Network;Medical;Medical center;medical schools;member;Mission;multi-ethnic;multi-site trial;Multicenter Trials;National Institute of Child Health and Human Development;Neonatal;Neonatal Intensive Care Units;Neonatology;Neurologic;Neurologist;Notification;Nursing Research;obstetric care;Obstetric pharmacology;obstetric services;Occupational Therapist;Ophthalmologist;Outpatients;Pathology;Patient Care;Patient Recruitments;patient retention;Patient Rights;Patients;Pediatric Neurology;Pediatrics;Perinatal;Persons;Physician Executives;Policies;Population;Positioning Attribute;Pravastatin;Pregnancy;Pregnant Women;premature;Premature Birth;prenatal;Prenatal care;Prenatal Diagnosis;Prevention;Procedures;Productivity;programs;Proteomics;Protocols documentation;Public Health;Publications;Publishing;Qualifying;Race;Radiology Specialty;recruit;Research;Research Design;Research Infrastructure;Research Personnel;sample collection;screening;Services;Site;stillbirth;System;Texas;Time;Translational Research;U-Series Cooperative Agreements;United States National Institutes of Health;Universities

PROJECT_TITLE: Maternal-Fetal Medicine Units Network


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Depression;Kidney Disease;Major Depressive Disorder;Mental Health;Mental Illness;Serious Mental Illness;Telehealth

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative The relevance to public health is providing urgently needed data on the efficacy and tolerability of 2 different treatments strategies, Behavioral Activation Teletherapy and antidepressant drug, for a Major Depressive Disorder (MDD) in Chronic Kidney Disease patients, disproportionately affected by MDD and its complications.

PI_NAMEs: HEDAYATI, SUSAN  (contact)

PROGRAM_OFFICER_NAME: GIPSON, DEBBIE SUE

PROJECT_TERMS: Address;Adherence;adverse outcome;Affect;anti-depressive agents;arm;attentional control;Behavior Therapy;Behavioral;Bupropion;C-reactive protein;Cessation of life;Chronic Kidney Failure;Clinic;Clinical;Clinical Management;clinical practice;Clinical Trials;Cognitive;Cognitive Therapy;Combination Drug Therapy;Combined Modality Therapy;comorbid depression;comparative efficacy;Control Groups;conventional therapy;Data;depressive symptoms;Dialysis procedure;Diet;Disease remission;Double-Blind Method;Dropout;efficacious treatment;End stage renal failure;Ensure;Equipoise;Fatigue;gastrointestinal;General Population;Goals;Health Care Visit;Health Services Accessibility;High Prevalence;Hospitalization;Improve Access;improved;improved outcome;Internet;Intervention;inventory of depressive symptomatology;Major Depressive Disorder;Mental Depression;Multicenter Trials;Nonpharmacologic Therapy;novel;novel strategies;novel therapeutics;Patient Preferences;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phase;Placebos;Plasma;poor sleep;primary endpoint;Public Health;Qualifying;Quality of life;Randomized;randomized trial;Randomized, Controlled Trials;Research;Research Personnel;Sampling;Sedation procedure;Selective Serotonin Reuptake Inhibitor;Sertraline;Single-Blind Study;Site;Sleep;Teletherapy;Testing;Travel;Treatment Efficacy;treatment strategy

PROJECT_TITLE: Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)

STUDY_SECTION: NRCS

STUDY_SECTION_NAME: Nursing and Related Clinical Sciences Study Section[NRCS]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative DNA double-strand break (DSB) repair is critical to maintain genomic stability mending DNA lesions that are induced by ionizing radiation and other common modalities of DNA damage-based anti-cancer therapies including topoisomerase I and II-targeted drugs as well as inhibitors of poly(ADP-ribose) polymerase (PARP). Homologous recombination involving BRCA2, single-strand annealing catalyzed by RAD52, and POLq-mediated end-joining are key cellular pathways for DSB repair. Our mechanistic findings are important for the understanding of the synthetic lethality network of BRCA2-defective cells, and the insights gained will help to stratify tumors that best respond to the inhibition of RAD52, POLq, and/or PARP.

PI_NAMEs: HEYER, WOLF-DIETRICH  (contact)

PROGRAM_OFFICER_NAME: WITKIN, KEREN L

PROJECT_TERMS: Abbreviations;Affect;Amino Acids;Base Pairing;Biochemical;Biochemical Reaction;Biological;brca gene;BRCA2 gene;Camptothecin;cancer cell;cancer health disparity;cancer therapy;Cell Cycle;Cells;Chromosomal Rearrangement;chromosome fusion;chromosome loss;Clinical;clinical application;Cyclin-Dependent Kinases;Data;Defect;DNA Binding;DNA biosynthesis;DNA Damage;DNA damage checkpoint;DNA Double Strand Break;DNA lesion;DNA Repair;DNA-Directed DNA Polymerase;Double Strand Break Repair;Drug Targeting;Gene Frequency;Genome;Genome Stability;Genomics;Goals;homologous recombination;homologous recombination deficiency;Immune checkpoint inhibitor;In Vitro;Individual;inhibitor;insight;Ionizing radiation;Knowledge;Laboratories;Latino Population;Length;loss of function;Malignant Breast Neoplasm;Mediating;Minor;Mitosis;Modality;Modeling;Mutagenesis;mutant;Nonhomologous DNA End Joining;novel;Odds Ratio;Onset of illness;Organoids;parent project;Pathway interactions;Patient Selection;Patients;personalized medicine;Poly(ADP-ribose) Polymerase Inhibitor;Poly(ADP-ribose) Polymerases;Polymerase;Predisposition;Process;Productivity;Property;protein purification;Proteins;Protocols documentation;RAD52 gene;Radiation induced damage;Reaction;Reactive Oxygen Species;reconstitution;Regimen;Regulation;repaired;Research;Resistance;response;Risk;Role;S phase;Side;Source;Testing;Therapeutic;Topoisomerase II;translational potential;tumor;Type I DNA Topoisomerases;Variant

PROJECT_TITLE: Regulation of DNA double-strand break repair pathway choice

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


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

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Public Health Narrative This research will determine how serum amyloid A (SAA), a protein that cleans up lipids from injured sites, aggregates in vital organs leading to organ damage in inflammation. This research will also determine how SAA and other aggregating proteins interact with amyloid modulators. These interactions play critical roles in ~40 life- threatening human disorders including Alzheimer’s, Parkinson’s and other amyloid diseases; research such as ours will help design much-needed treatments for these incurable diseases.

PI_NAMEs: GURSKY, OLGA  (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: alpha synuclein;Alzheimer's Disease;Amyloid;Amyloid beta-Protein;Amyloid deposition;amyloid formation;Amyloid Proteins;Amyloidosis;Apolipoprotein E;Binding;Biochemical;Biological Assay;biophysical techniques;Cessation of life;Chronic;Clinical Trials;Complex;Complication;Computing Methodologies;Cryoelectron Microscopy;Deposition;design;Disease;Drug Design;Electrons;Enzyme-Linked Immunosorbent Assay;Failure;fascinate;fibrillogenesis;Glycosaminoglycans;Goals;Health;Homeostasis;Human;Inflammation;injured;Injury;insight;Life;Ligands;Link;Lipid Binding;Lipids;Lipolysis;Lipoproteins;liver injury;Methods;Microscopic;mimetics;Modeling;molecular dynamics;Mus;nanoparticle;Nerve Degeneration;Organ;Parkinson Disease;Pathologic;Pathway interactions;Patients;Pharmaceutical Preparations;Pilot Projects;Plasma Proteins;Play;protein aggregation;Proteins;Public Health;Recombinants;reconstitution;renal damage;Research;Role;scaffold;Serum amyloid A protein;Site;small molecule;Structure;tau Proteins;Testing;therapeutic target;tool

PROJECT_TITLE: Structure and Function of Serum Amyloid A in Health and Disease

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


NIH_SPENDING_CATS: Aging;Genetics;Human Genome

ORG_CITY: GAINESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: We have shown that disruption of the muscle circadian clock mechanism through loss of the core clock gene, Bmal1, is sufficient to induce significant muscle weakness and surprisingly, increased mortality. Based on these findings, the overall objective of this grant is to pursue the fundamental understanding of the role of the muscle circadian clock in regulating a daily program of gene expression and how clock disruption leads to significant muscle weakness and diminished systemic health.

PI_NAMEs: ESSER, KARYN A (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: 3-Dimensional;adeno-associated viral vector;adenovirus mediated delivery;Adult;Aging;Antibodies;ARNTL gene;Attention;Binding;Bioluminescence;ChIP-seq;Chromatin;Chronic Disease;circadian pacemaker;cofactor;connectin;Coupled;Data;DNA Binding;Dose;Elements;epigenomics;Exhibits;experimental study;extend lifespan;Female;functional outcomes;Gene Expression;Genes;Genetic;Genome;Genomics;Grant;Health;improved;Knockout Mice;Length;life span;Link;loss of function mutation;male;Measures;Messenger RNA;metabolomics;Microfilaments;Modeling;Molecular;mortality;mouse model;Muscle;Muscle function;muscle strength;Muscle Weakness;Muscular Atrophy;Myopathy;Outcome;Output;Pathology;Phenotype;Physiological;programs;promoter;Property;Proteins;Regulation;RNA Splicing;Role;Sarcomeres;Site;Skeletal Muscle;Structure;superresolution microscopy;Techniques;Testing;Thick Filament;Tissues;transcription factor;transcriptome sequencing;transcriptomics;translational approach

PROJECT_TITLE: Circadian Clock and Muscle Health

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]