NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Climate-Related Exposures and Conditions;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Microbiome;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Social Determinants of Health

ORG_CITY: CHESTNUT HILL

ORG_NAME: BOSTON COLLEGE

ORG_STATE: MA

PHR: Project Narrative  Air pollution represents one of the largest public health burdens world-wide and is associated with increased risk of many neuropsychiatric disorders that are characterized by social dysfunction, including autism spectrum disorder (ASD). This project seeks to understand how prenatal exposure to a combination of air pollution and maternal stress (which unmasks vulnerability to environmental toxins) synergize to produce dysbiosis of the gut microbiome, and consequently, disruption of the neuro-immune mechanisms that regulate social behavior. The results of these experiments will answer outstanding questions about the relationship between the gut microbiome and the social brain and how this is impacted by environmental toxin exposure.

PI_NAMEs: SMITH, CAROLINE JACKSON (contact)

PROGRAM_OFFICER_NAME: DZIERLENGA, ANIKA LIN

PROJECT_TERMS: Affect;Air Pollution;Animal Model;autism spectrum disorder;Birth;Brain;brain cell;career;career development;Child;Communication;Data;deprivation;Diesel Exhaust;Disease;Dopamine;dopamine system;Environmental Impact;Etiology;experimental study;Exposure to;Fostering;Foundations;Funding;Future;gastrointestinal symptom;gut dysbiosis;gut microbiome;gut-brain axis;Immune;Impairment;individuals with autism spectrum disorder;Link;male;marginalized community;maternal stress;Mediating;metagenomic sequencing;Metagenomics;microbial;microbiome;Microglia;Modeling;Molecular;mouse model;Neuroimmunomodulation;neuropsychiatric disorder;novel;offspring;particle;Pathway interactions;Play;pollutant;prenatal exposure;prevent;Psychosocial Stress;Public Health;pup;Research;Resources;Rewards;Risk;Signal Transduction;social;Social Behavior;social deficits;Social Development;social disparities;Social Interaction;Stress;stressor;Support System;synergism;Testing;Toxic Environmental Substances;United States

PROJECT_TITLE: Effects of air pollution/maternal stress on microglial sculpting of social circuits.

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: Columbus

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OPHTHALMOLOGY

ORG_FIPS: US

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Alzheimer’s disease (AD) is the most common form of dementia worldwide. Detailed understanding of the molecular processes underlying the development of the disease is critical for future therapeutics. The primary goal of this project is to assess the contribution of pathways involved in NAD metabolism and cGAS-STING pathway.

PI_NAMEs: KERUR, NAGARAJ  (contact)

PROGRAM_OFFICER_NAME: KELLY, HALONNA R

PROJECT_TERMS: Accounting;Alzheimer's Disease;Alzheimer's disease model;Animal Model;Cell Culture Techniques;Cellular Stress;Dementia;Development;Disease;DNA Damage;DNA Repair;Future;Goals;hallmarks of aging;Homeostasis;Impairment;Inflammation;insight;Link;Metabolism;mitochondrial dysfunction;Molecular;Mus;Nerve Degeneration;normal aging;novel;Pathogenesis;Pathologic;Pathway interactions;Play;Process;response;Role;Signal Transduction;Stimulator of Interferon Genes;Therapeutic

PROJECT_TITLE: Non-canonical cGAS signaling in DNA damage response

STUDY_SECTION: CSRS

STUDY_SECTION_NAME: Cellular Signaling and Regulatory Systems Study Section[CSRS]


ADMINISTERING_IC: AG

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Bioengineering;Brain Disorders;Cerebrovascular;Dementia;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Physical Activity;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Prevention;Rehabilitation;Stroke;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: BALTIMORE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: 8. Project Narrative: Overall The increased life expectancy of older Americans makes the maintenance of functional independence a major public health priority. The functional impairments and disabilities that occur in older people can emanate from acute events, such as stroke, heart attack, and hip fracture, or reflect the progression of chronic diseases. The UM-OAIC’s outstanding environment for research and research training in geriatrics, exercise, and rehabilitation sciences allows investigators from multiple disciplines to work together to develop and test novel exercise and activity-based and multi-modal rehabilitation interventions to restore function and minimize disability following acute disabling events and gradual declines related to serious chronic diseases.

PI_NAMEs: KATZEL, LESLIE I.;MAGAZINER, JAY  (contact);RYAN, ALICE S.

PROGRAM_OFFICER_NAME: JOSEPH, LYNDON

PROJECT_TERMS: Academy;Acute;Aerobic;Affect;Aging;aging process;Alzheimer's disease related dementia;American;Animal Model;animal old age;Area;bench to bedside;Biometry;Body System;career;Caring;Cessation of life;Chronic Disease;Clinic;Clinical;clinical center;clinically relevant;Collaborations;Communities;community advisory board;community setting;Degenerative polyarthritis;design;Development;disability;disabled;Disablement;Disabling;Disabling condition;disabling disease;Discipline;Disease Pathway;education research;efficacy testing;Engineering;Enrollment;Environment;Evaluation;Event;Exercise;Faculty;Fatigue;frailty;functional disability;Functional impairment;functional improvement;functional independence;functional restoration;Funding;Future;Geriatrics;Health Promotion;Heart failure;Hip Fractures;Home;Impaired cognition;Impairment;improved;Incidence;industry partner;Informatics;innovation;Institutionalization;Intervention;Knowledge;Laboratories;Leadership;Life Expectancy;Maintenance;Malignant Neoplasms;Medical;Mentors;Mission;multimodality;Myocardial Infarction;Neuronal Plasticity;new technology;next generation;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Obesity;older adult;Older Population;operation;Outcome;Parkinson Disease;physical impairment;Physiological;Physiology;pre-clinical;prevent;Prevention;Process;programs;public health priorities;rehabilitation research;rehabilitation science;rehabilitation technology;Rehabilitation therapy;Research;Research Personnel;Research Training;Resources;restoration;Risk;Robotics;sarcopenia;SARS-CoV-2 infection;Scientist;Services;Stroke;Technology;Testing;Training;Translating;translational pipeline;Translational Research;Traumatic Brain Injury;Treatment Efficacy;Underrepresented Minority;Vascular Diseases;Work

PROJECT_TITLE: Incidence and impact of traumatic brain injury among older adults with Alzheimer's disease and related dementias


ADMINISTERING_IC: HL

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Hematology;Immunotherapy;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative Acute and chronic graft-versus host disease (GVHD) remain one of the major complications in allogeneic transplantation, occurring in 40-70% of recipients, particularly when peripheral blood stem-cells are used. We have compelling evidence that co-stimulation blockade with abatacept (CTLA-4 Ig) can significantly reduce grades II-IV and III-IV acute GVHD and that B-cell depletion can prevent and treat the most serious complications of chronic GVHD, while others have shown that post-transplant cyclophosphamide (PTCy) is a powerful strategy to reduce severe acute and chronic GVHD. This study will help us define the superior strategy to prevent acute and chronic GVHD without compromising the graft-versus-tumor effect by comparing the following two rational strategies in a randomized fashion: Abatacept/Tacrolimus/Methotrexate/Obinutuzumab maintenance and PTCy/Tacrolimus/Mycophenolate mofetil.

PI_NAMEs: ANTIN, JOSEPH H (contact)

PROGRAM_OFFICER_NAME: DI FRONZO, NANCY L

PROJECT_TERMS: Acute;Acute Graft Versus Host Disease;Allogenic;Antibodies;Antigen-Presenting Cells;arm;Autologous;B-Lymphocytes;Bone Marrow Transplantation;CD28 gene;Cell Communication;chronic graft versus host disease;Clinic;Creativeness;CTLA4 gene;Cyclophosphamide;cytokine;Dana-Farber Cancer Institute;Development;Disease Outcome;Disease-Free Survival;disorder prevention;Functional disorder;Future;Generations;Goals;Graft Rejection;graft vs host disease;graft vs leukemia effect;Graft-Versus-Tumor Induction;hazard;Hematocrit procedure;Homologous Transplantation;Human;Humoral Immunities;immune reconstitution;Immunologics;immunoregulation;Immunosuppression;in vivo;Infection;infection rate;insight;Maintenance;Methotrexate;Modeling;Monoclonal Antibodies;MS4A1 gene;Multicenter Studies;Mus;Mycophenolate;mycophenolate mofetil;nonhuman primate;Opportunistic Infections;Organ;Patient-Focused Outcomes;Peripheral Blood Stem Cell;Phase;Play;post-transplant;prevent;Prevention;Prevention strategy;Principal Investigator;prophylactic;Prophylactic treatment;Randomized;randomized trial;randomized, clinical trials;Randomized, Controlled Trials;Recovery;Regimen;Relapse;Resolution;rituximab;Role;secondary outcome;standard of care;Structure of germinal center of lymph node;survival outcome;T-Lymphocyte;Tacrolimus;Testing;theories;Therapeutic;Time;tositumomab;Toxic effect;Translating;Transplantation;trial comparing;two-arm study;Work;Writing

PROJECT_TITLE: BMT CTN Core - Dana-Farber Cancer Institute and MGH Consortium

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-L (M1)]


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: TEMPE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: PUBLIC PURPOSE We propose to renew a collaborative project that will advance our understanding of human health and disease. We will utilize new innovative strategies to expand an existing research resource for scientists. Validation experiments in our labs employing strains from our resource have shed new light on basic biological mechanisms such as gene regulation and alternative splicing as well as provided new avenues for the analysis of human health and disease.

PI_NAMEs: NEWFELD, STUART J (contact)

PROGRAM_OFFICER_NAME: ZOU, SIGE

PROJECT_TERMS: activin B;Address;Adult;Advisory Committees;Aging;Alleles;Alternative Splicing;Arizona;Attention;Biochemical;Biological;Biology;Blood - brain barrier anatomy;Brain;chromosome loss;Chromosomes;Clone Cells;Code;Communities;Companions;Complement;Complementary DNA;cost;Data;Databases;Deposition;Development;Disease;Drosophila genus;Drosophila melanogaster;experimental study;Eye;Family member;fly;FlyBase;frontier;Funding;gain of function;Gene Expression Regulation;gene function;gene interaction;Genes;Genetic;genetic analysis;Genetic Recombination;Genetic Screening;genome resource;Genotype;Goals;Grant;Health;Homologous Gene;Human;Indiana;Individual;innovation;loss of function;Medical;Minnesota;Modernization;Molecular;Mutagens;mutant;Mutation;Neurons;null mutation;Occupations;Paper;Partner in relationship;Phenotype;Protein Analysis;Proteins;Publications;Publishing;R24;Reporting;repository;Research;Research Personnel;Resources;RNA Interference;Scientist;Stains;Sterility;Testing;Time;TNFSF5 gene;Transcript;Transforming Growth Factor beta;Transgenes;Transgenic Organisms;translational applications;United States National Institutes of Health;Validation

PROJECT_TITLE: Comprehensive Resource for the Drosophila 4th chromosome

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Digestive Diseases;Infant Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rare Diseases

ORG_CITY: CHAPEL HILL

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative Necrotizing enterocolitis (NEC) is a devastating consequence of prematurity that results from an aberrant pro- inflammatory immune response and leads to intestinal necrosis. In the United States, NEC has a mortality rate that can approach 50% and is responsible for 1 in 10 deaths in the neonatal intensive care unit. My innovative research program is dedicated to preventing and curing this deadly disease through studies focused on mechanisms of disease pathogenesis, identification of early disease biomarkers, and development of targeted preventative and therapeutic strategies to improve outcomes for these vulnerable neonates.

PI_NAMEs: GOOD, MISTY L (contact)

PROGRAM_OFFICER_NAME: LOH, KATRINA SHUEH WEN

PROJECT_TERMS: Acceleration;Age;Award;biobank;Biological Markers;Biological Response Modifier Therapy;catalyst;Cessation of life;cohort;Country;Critical Illness;cytokine;Death Rate;Dedications;design;Development;developmental disease;Developmental Process;Disease;Early identification;effective therapy;Future;Growth and Development function;Human;Immune response;Immunity;Immunologics;Immunotherapy;improved outcome;Infant;Inflammation;Inflammatory;Inflammatory Response;innovation;insight;Institution;interleukin-22;Interruption;Intervention;Intestinal Diseases;intestinal epithelium;intestinal injury;Intestines;Laboratories;Legal patent;National Institute of Diabetes and Digestive and Kidney Diseases;Necrosis;Necrotizing Enterocolitis;Neonatal Intensive Care Units;neonate;novel;Operative Surgical Procedures;Pathogenesis;Patients;pre-clinical research;premature;Premature Infant;preterm newborn;prevent;programs;prospective;Research;Research Personnel;Research Support;Resected;response;Role;Sampling;Techniques;Therapeutic;Tissues;United States

PROJECT_TITLE: Reprogramming intestinal immunity in preterm neonates to prevent and cure necrotizing enterocolitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-S (M3)]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Services;Nutrition;Obesity;Prevention;Telehealth

ORG_CITY: PHILADELPHIA

ORG_DEPT: PSYCHOLOGY

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: Narrative Evidence-based interventions for overweight and obesity are underutilized. This project is designed to test a program in which participants are provided with a weight loss navigator who will help them understand their options for evidence-based weight loss intervention and who will promote initiation and continued engagement with an intervention option. The project will provide information about how well received the navigator program is and the extent to which it works as expected.

PI_NAMEs: BUTRYN, MEGHAN  (contact)

PROGRAM_OFFICER_NAME: HALES, CRAIG MAURICE

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Adult;Alternative Therapies;Area;bariatric surgery;barrier to care;Behavioral;Benchmarking;Body mass index;Body Weight decreased;Climate;clinical practice;Clinical Trials;clinically significant;Communication;Communities;Continuity of Patient Care;cost;Cost Analysis;Counseling;Data;Decision Making;design;Diet;dietary;Dietary intake;dieting;Disease;Drug Prescriptions;Education;Educational workshop;effective intervention;efficacy evaluation;efficacy testing;enhanced care;evidence base;Evidence based intervention;Evidence based treatment;Feedback;follow-up;Funding;Funding Opportunities;Future;Health;Healthcare;Healthcare Systems;improved;Individual;innovation;interest;Intervention;intervention effect;Knowledge;Licensing;Literature;Measurement;Mediator;meetings;Mission;Monitor;Motivation;National Institute of Diabetes and Digestive and Kidney Diseases;Obesity;Operative Surgical Procedures;Overweight;Participant;patient navigator;pharmacologic;Physical activity;preference;premature;prevention service;primary outcome;Problem Solving;Process;programs;Protocols documentation;Public Health;Quality of life;Randomized;recruit;remote assessment;remote delivery;Research;Research Project Grants;response;Role;Sampling;satisfaction;Self Direction;Signal Transduction;Source;Specific qualifier value;Standardization;Structure;Supervision;Testing;Text Messaging;tool;Training;treatment services;uptake;video chat;Visit;Weight;weight loss intervention;wireless;Work

PROJECT_TITLE: Piloting a patient navigator program to facilitate uptake and persistence with evidence-based weight loss interventions

STUDY_SECTION: LCBH

STUDY_SECTION_NAME: Lifestyle Change and Behavioral Health Study Section[LCBH]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences

ORG_CITY: ROCHESTER

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Project Narrative Hearing in noisy listening environments is an everyday challenge that increases in difficulty with hearing loss and normal aging. The proposed research in an animal model advances our understanding of the basic neural mechanisms for perception of amplitude-modulated sounds in noise, which are currently poorly understood. Expanded knowledge of this critical hearing-in-noise mechanism will help lay the groundwork needed for efforts aimed at restoring auditory perceptual abilities in people with hearing loss, ultimately improving quality of life.

PI_NAMEs: HENRY, KENNETH STUART (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: Acoustic Nerve;Acoustics;Animal Model;animal model development;Animals;Area;Auditory;auditory processing;base;Behavioral;behavioral study;Birds;Brain region;cell type;Cells;Code;Complex;design;Development;Environment;experimental study;extracellular;Frequencies;Hearing;hearing impairment;Human;Hyperacusis;improved;innovation;insight;Knowledge;Literature;Mammals;Masks;Measurement;Melopsittacus;Midbrain structure;Modeling;Nerve Fibers;neural;neural circuit;neural correlate;neuromechanism;Neurons;neurophysiology;Noise;noise perception;normal aging;Operant Conditioning;Parakeets;Pathway interactions;Perception;Performance;Persons;Physiological;Procedures;Prosencephalon;Psychophysics;Quality of life;Research;response;Role;Scheme;sound;Source;Speech;speech in noise;Speech Perception;Stimulus;Structure;Testing;Theoretical Studies;Time;Training;Variant

PROJECT_TITLE: Neural bases of masked amplitude-modulation perception

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Building Research Capacity at Institutions with Limited NIH Funding;Comparative Effectiveness Research;Cost Effectiveness Research;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Rural Health;Social Determinants of Health

ORG_CITY: FRESNO

ORG_DEPT: BIOLOGY

ORG_NAME: CALIFORNIA STATE UNIVERSITY FRESNO

ORG_STATE: CA

PHR: Project Narrative Surveillance of antimicrobial resistance has traditionally been centralized to research-focused institutes due to the high cost associated with pathogen identification. Given the recent advances in long-read sequencing technologies, we now have the potential to identify pathogens and even antimicrobial bacteriophages with low- cost resources. It is imperative to test the capacity of long-read sequencing in the context of AMR, to reinvent the surveillance of local infection outbreaks as a low-cost decentralized system, where resource-constraint institutes such as California State University, Fresno can play a proactive role in monitoring and investigating drug-resistant bacteria.

PI_NAMEs: SHIM, HYUNJIN  (contact)

PROGRAM_OFFICER_NAME: SASTALLA, INKA I

PROJECT_TERMS: adverse outcome;Affect;agricultural activity;agricultural region;Agriculture;Antibiotics;antimicrobial;Antimicrobial Resistance;Bacteria;Bacterial Genome;Bacterial Infections;Bacteriophages;Benchmarking;Biological Assay;Biological Response Modifier Therapy;California;Cattle;Chemistry;Communities;cost;cost effective;cost effectiveness;cost efficient;County;Data;Data Analyses;Data Collection;Data Set;Decentralization;Disease Outbreaks;Disparity;Doctor of Medicine;Doctor of Philosophy;drug resistant bacteria;drug resistant pathogen;drug testing;empowerment;Environment;extensive drug resistance;Eyedrops;Farm;Focal Infection;Follow-Up Studies;Future;Genome;Genomics;Goals;Healthcare;Human;India;Infection;Infiltration;invention;Investigation;Investments;manufacture;Medicine;Metagenomics;Methods;Monitor;Multi-Drug Resistance;nanopore;Nature;novel;Paper;pathogen;Patients;Peer Review;Performance;Persons;Play;Prevention;Pseudomonas aeruginosa;Public Health;Publishing;Quantitative Evaluations;Research;Research Institute;Resolution;Resource-limited setting;Resources;Role;Running;Sampling;sequencing platform;Societies;source localization;Superbug;System;Technology;Testing;Time;timeline;underserved community;United States;United States National Institutes of Health;Universities;Update;Work

PROJECT_TITLE: Surveillance of drug-resistant bacteria in resource-limited settings: a focus on cost-effective long-read sequencing of eyedrop-associated P. aeruginosa and locally sourced metagenomic samples

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 SPJ-D (M1)]


NIH_SPENDING_CATS: Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Kidney Disease;Organ Transplantation;Racial and Ethnic Minority Health Research;Transplantation

ORG_CITY: WINSTON-SALEM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: . Protein levels of apolipoprotein L1 (APOL1) and other biomarkers in donor kidney tissue from African Americans at the time of transplantation may more accurately assess the likelihood of shorter kidney transplant survival than risks imparted by donor and recipient APOL1 genotypes, and other genetic and non-genetic factors. This application, an ancillary study from the NIH-sponsored APOL1 Long-term Kidney Transplant Outcomes Network (APOLLO) Consortium, seeks to evaluate effects of APOL1 protein levels, APOL1 genotype, and expression of APOL1 and other genes in donor kidneys using state of the art approaches on outcomes after transplantation of kidneys from African American deceased donors. Our results could transform the process of organ allocation in kidney transplantation and optimize survival of transplanted kidneys in the growing numbers of patients with end-stage kidney disease for whom transplantation is their best treatment option.

PI_NAMEs: FREEDMAN, BARRY IRA (contact);MA, LIJUN

PROGRAM_OFFICER_NAME: PARSA, AFSHIN

PROJECT_TERMS: Accounting;Address;Affect;African;African American;African American population;Allografting;Ancillary Study;Apolipoproteins;Biological Assay;Biological Markers;Biopsy;Caring;cell type;Cells;Chronic Kidney Failure;Clinical;Clinical Pathways;clinically actionable;cost;cytotoxicity;Data;Development;Dialysis procedure;differential expression;Discrimination;disease disparity;Disparity;disparity reduction;DNA;Dose;Economics;End stage renal failure;Endothelial Cells;Equilibrium;Failure;Funding;Future;Gene Expression;Gene Expression Profile;gene interaction;Gene Proteins;Genes;Genetic;genome-wide;genomic locus;Genomics;Genotype;glomerular endothelium;Goals;graft failure;Graft Survival;health care availability;health disparity;Health Services Accessibility;high risk;Home;Human;Implant;implantation;improved;indexing;Individual;Inherited;interstitial;Investigation;Kidney;kidney allograft;kidney biopsy;Kidney Diseases;Kidney Failure;Kidney Transplantation;Link;Mediating;Medicare;Messenger RNA;Molecular;nephrogenesis;non-genetic;novel;Operating Rooms;organ allocation;Other Genetics;Outcome;overexpression;Pathway interactions;Patients;Perioperative;podocyte;Population;precision medicine;preservation;primary outcome;Process;prospective;Prospective Studies;Proteins;Proteinuria;Public Health;Quality of life;Quantitative Trait Loci;rapid test;rapid testing;Reagent;Recommendation;Renal function;Renal tubule structure;Reporting;Reproducibility;Research;Risk;risk variant;RNA;Sampling;secondary outcome;single-cell RNA sequencing;social;Socioeconomic Factors;Source;Testing;Text;Time;Tissues;Toxic effect;Transcript;transcriptome;transcriptome sequencing;transcriptomics;transgene expression;transplant model;Transplant Recipients;Transplantation;Trust;United Network for Organ Sharing;United States National Institutes of Health;Variant;Work

PROJECT_TITLE: Trans-omics Analysis of African American Deceased Donor Kidneys for Transplant Outcomes.

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Burden of Illness;Caregiving Research;Clinical Research;Dementia;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurodegenerative;Neurosciences;Palliative Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: HOUSTON

ORG_NAME: RICE UNIVERSITY

ORG_STATE: TX

PHR: PROJECT NARRATIVE Our objective in this proposal is to provide biobehavioral evidence in support of the idea that discrimination compounds stress in minority populations, and to apply this model of compounding stress to ADRD spousal caregivers. By identifying discrimination as a key factor contributing to disease burden and premature aging in the largest minority in the United States, we may be able to reduce disease burden and chronic stress in underprivileged communities. Additionally, we may be able to learn more about the factors that promote adverse health outcomes in ADRD spousal caregivers.

PI_NAMEs: FAGUNDES, CHRISTOPHER PAUL (contact)

PROGRAM_OFFICER_NAME: HOOKER, EMILY DIANE

PROJECT_TERMS: Adult;Affect;Aging;Alzheimer's disease related dementia;biobehavior;Blood;burden of chronic illness;burden of illness;Caregiver Burden;Caregivers;caregiving;Caring;Cell Aging;Chronic stress;Communities;cytokine;Dementia caregivers;depressive symptoms;Discrimination;Disease;experience;Future;Goals;Grief reaction;Health;immune function;indexing;Inflammation;Inflammatory;Intervention;Latino;Learning;Lipopolysaccharides;Loneliness;Measures;Mediating;Minority;Minority Groups;minority stress;Mitochondria;Modeling;Non-Insulin-Dependent Diabetes Mellitus;Outcome;parent project;Personal Satisfaction;physical conditioning;Premature aging syndrome;Production;Psyche structure;Quality of life;Race;racial discrimination;Reporting;Research Personnel;Risk;Role;Social isolation;Spouse Caregiver;Spouses;Stress;Symptoms;United States

PROJECT_TITLE: Cuidar, intentar, y lastimar (To care, try, and hurt): The Biobehavioral Role of Discrimination in ADRD Spousal Caregiving


ADMINISTERING_IC: GM

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Rare Diseases

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Heparan sulfate (HS) proteoglycans play critical roles development, homeostasis, pathogen infection, and disease development. HS polysaccharides are essential in metazoan organisms and heterozygous defects lead to skeletal and connective tissue disease. Our goals are to provide a structural understanding of HS synthesis and insights into how defects lead to pathology. Unraveling the mechanisms governing HS backbone synthesis will shed light on the molecular basis of HS-mediated cellular processes and potentially for targeted interventions.

PI_NAMEs: MOREMEN, KELLEY W. (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Active Sites;Address;analog;Benign;Binding;Biochemical;Biochemistry;Biology;bone;Cartilage;Catalysis;Catalytic Domain;Cell Line;Cell Physiology;Cell surface;Cell Survival;Charge;Chondrogenesis;Clinical;Complex;Connective Tissue Diseases;Data;Defect;design;Development;Disaccharides;Disease;Embryo;Enzymatic Biochemistry;Enzymes;epimerization;Exostoses;EXT1 gene;EXT2 gene;EXTL3 gene;Extracellular Matrix;Future;Gene Targeting;Goals;Growth Factor;Health;Heparan Sulfate Biosynthesis;Heparan Sulfate Proteoglycan;Heparitin Sulfate;Hereditary Multiple Exostoses;Heterozygote;Homeostasis;Homologous Protein;Human;In Vitro;in vitro Assay;in vivo;Individual;Infection;innovation;insight;Intervention;Knock-in;Lead;Length;Ligaments;long bone;loss of function;Loss of Heterozygosity;Malignant Neoplasms;Maps;Mediating;migration;Modification;Molecular;monomer;morphogens;Mutagenesis;mutant;Mutation;Nature;neural;new therapeutic target;Organism;Outcome;pathogen;Pathogenesis;Pathology;Pathway interactions;Play;Polymerase;Polymers;Polysaccharides;Process;protein complex;Proteins;Proteoglycan;proteoglycan core protein;receptor;Research;Role;Signal Transduction;skeletal tissue;Structure;Substrate Interaction;sugar;Sulfate;sulfated polymer;Syndrome;Testing;Therapeutic Intervention;therapeutic target;Tissues;Transferase;tumor;UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase;Vertebral column

PROJECT_TITLE: Heparan sulfate co-polymerase function and defects in disease

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cancer;Clinical Research;Data Science;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Prevention;Rare Diseases;Social Determinants of Health

ORG_CITY: NISKAYUNA

ORG_NAME: GE MEDICAL SYSTEMS INFORMATION TECHNOLOGIES, INC

PHR: PROJECT NARRATIVE We will develop and deploy an affordable automated point-of-care (POC) telecytology platform for oral cancer screening in India that will reliably establish a diagnosis of oral cancer in the community setting and create an immediate referral care pathway. This will save significant time in reaching a diagnosis (same day vs. ~7 months) and improve outcomes via earlier patient treatment.

PI_NAMEs: GINTY, FIONA  (contact)

PROGRAM_OFFICER_NAME: TANDON, PUSHPA

PROJECT_TERMS: Accreditation;Algorithms;Annual Reports;Artificial Intelligence;artificial intelligence algorithm;artificial intelligence model;artificial neural network;automated algorithm;Biopsy;Biopsy Specimen;Brazil;Cancer Center;Cancer Hospital;Cancer Patient;Caring;Cell model;Cells;Cellular Phone;Cessation of life;China;Clinical;cloud platform;Communities;community setting;Community Trial;cost;Custom;Cytology;Data;design;Devices;Diagnosis;Diagnostic;diagnostic platform;diagnostic tool;Early Diagnosis;Early treatment;Economics;Evaluation;Expenditure;fabrication;Glass;Goals;Head;Head and Neck Cancer;Head and neck structure;Health;high risk;Hospitals;Image;improved;improved outcome;Incidence;India;Individual;innovation;Insurance;Lesion;malignant mouth neoplasm;Malignant Neoplasms;Medical;mid-career faculty;mobile application;multidisciplinary;NCI Center for Cancer Research;Network-based;Oncology;Oncology Group;Optics;Oral;Oral cavity;Oral Diagnosis;Outcome;outreach;Pathologist;Pathology;Pathway interactions;patient screening;Patient Triage;Patients;Performance;performance tests;point of care;point-of-care detection;Population;population based;portability;Predictive Analytics;Probability;prototype;Public Health;Reporting;Research;Resolution;risk stratification;routine screening;Running;Rural;Rural Community;rural environment;rural health clinic;Russia;sample collection;Sampling;Scanning;Science;screening;Screening for Oral Cancer;screening program;Secure;Services;Slide;social;South Africa;Stage at Diagnosis;Stains;Survival Rate;Symptoms;System;tertiary care;Time;Tolonium chloride;tool;Training;transmission process;treatment planning;treatment program;Triage;Validation;vibration;Vision;Visual;Work

PROJECT_TITLE: Point of Care Detection and Diagnosis of Oral Cancer using a Low Cost Imaging Module enabled by AI

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 TCRB-Q (M1)]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Disability Research;Health Services;Hematology;Mental Health;Pain Research;Palliative Care;Physical Activity;Prevention;Regenerative Medicine;Rehabilitation;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: DURHAM

ORG_DEPT: PSYCHIATRY

ORG_NAME: DUKE UNIVERSITY

PHR: Relevance This research is relevant to public health and NIH’s mission because it aims to enable patients who have undergone hematopoietic stem cell transplant (HCT) to effectively cope with multiple, interfering symptoms – fatigue, pain, and distress – to improve their ability to engage in physical activity that can improve physical disability. Demonstration of efficacy will allow for (1) increased access to and implementation of an efficacious intervention, ultimately reducing long-term suffering caused by cancer and HCT therapy and (2) future work generalizing this efficacious intervention to the growing number of healthcare systems across the US providing HCT patients with home-based care, as well as to other types of cancer and/or chronic disease populations with a similar comorbid symptom presentation. Positive results could lead to a paradigm shift in outpatient care for a cancer patient population who experiences high symptom burden and disability.

PI_NAMEs: KELLEHER, SARAH  (contact)

PROGRAM_OFFICER_NAME: STRECK, BRENNAN PARMELEE

PROJECT_TERMS: Accelerometer;Address;age acceleration;aggressive therapy;Ambulatory Care;associated symptom;Behavior Therapy;Behavioral;behavioral health intervention;Behavioral Symptoms;Biological Markers;Biometry;Cancer Etiology;Cancer Patient;cancer stem cell;cancer type;care coordination;Caring;Chronic Disease;Cognitive;coping;Coping Skills;Data;debilitating symptom;design;digital;Digital biomarker;disability;disability burden;Distress;Educational process of instructing;efficacious intervention;efficacy testing;evidence base;Exercise;exercise intervention;experience;Fatigue;Feedback;fitbit;Focus Groups;Future;Guidelines;Health;Health Benefit;Health Technology;Healthcare Systems;Heart Rate;Hematology;Hematopoietic Stem Cell Transplantation;Home;Hybrids;improved;Infection;innovation;Intervention;intervention delivery;Lead;Life;Life Expectancy;Literature;Malignant Neoplasms;Measures;Medical;Medical center;member;mHealth;Mission;mobile application;novel;Occupational Therapy;Oncology;Outcome;Pain;Participant;patient population;Patient Self-Report;Patient-Focused Outcomes;Patients;persistent symptom;Persons;Physical activity;physically handicapped;Physiological;pilot test;Play;Population;post-transplant;primary outcome;programs;Protocols documentation;Psychiatry;psychological distress;Public Health;Randomized, Controlled Trials;real time monitoring;Recommendation;Recovery;Recurrent disease;reduce symptoms;Reporting;Research;Rest;Risk;Role;secondary outcome;Self Efficacy;Severities;Signal Transduction;skills training;Sleep;Social isolation;standard care;Stem cell transplant;Symptom Burden;symptom management;Symptoms;Technology;Testing;therapy design;Time;Transplant Recipients;Transplantation;transplantation therapy;treatment as usual;United States National Institutes of Health;Videoconferencing;Walking;wireless;Work

PROJECT_TITLE: Randomized Controlled Trial of a Hybrid-Delivered Cognitive Behavioral Symptom Management and Activity Coaching Intervention for Stem Cell Transplant Patients

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


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Hematology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: NARRATIVE The Blood and Marrow Transplant Clinical Trials Network conducts clinical trials to improve outcomes for patients facing life-threatening diseases. The Mount Sinai BMT CTN Consortium will advance the mission of the BMT CTN by enrolling patients onto BMT CTN clinical trials and providing scientific leadership to the BMT CTN. The proposed clinical trial will mitigate graft-versus-host disease, the most serious HCT complication.

PI_NAMEs: LEVINE, JOHN  (contact)

PROJECT_TERMS: Acute;Acute Graft Versus Host Disease;Adult;Allogenic;Biological Assay;Biological Markers;Blood;Bone Marrow;Bone Marrow Transplantation;Cell Therapy;Child;Clinic;Clinical Trials;Clinical Trials Network;Collaborations;Complication;Conduct Clinical Trials;Data;Databases;Disease;Disease Resistance;Effector Cell;Enrollment;Goals;graft vs host disease;Hematological Disease;Immune;improved;improved outcome;Infusion procedures;innovation;International;Intervention;Leadership;Life;Manufacturer;Medical;mesenchymal stromal cell;Mission;Natural History;Non-Malignant;participant enrollment;Patient-Focused Outcomes;Patients;Productivity;Refractory;Resistance;Sickle Cell Anemia;Steroids;Survival Rate;Testing;Toxic effect;transplant centers;Transplantation;Underrepresented Minority;virtual

PROJECT_TITLE: BMT CTN Core - Mount Sinai Consortium


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Sleep Research

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Narrative Sleep deficiency is common and detrimental in persons with Alzheimer's disease and related dementias (ADRD), but improved sleep measures are needed to understand of the relationship between sleep and neurocognitive function in ADRD. The goals of the proposed research are to characterize sleep deficiency in persons with ADRD using feasible, accurate, and comprehensive measures and to evaluate the cross-sectional relationships between sleep deficiency, markers of neuronal damage/plasticity, and ADRD pathology. The work proposed may elucidate mechanisms linking sleep deficiency and neurodegeneration and establish targets for future sleep- promoting interventions, ultimately helping to slow progression of disease and improve quality of life in persons with ADRD.

PI_NAMEs: MINER, BRIENNE  (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: actigraphy;adverse outcome;Affect;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid beta-42;Amyloid beta-Protein;Architecture;Award;axon injury;Biological Markers;Brain-Derived Neurotrophic Factor;circadian;Circadian Rhythms;Clinical;Cognition;Data;Dementia;Deposition;design;Devices;Disease Progression;Electroencephalography;Enrollment;Exclusion;experience;functional decline;Future;glymphatic clearance;glymphatic function;Goals;Home;Impaired cognition;Impairment;improved;improvement on sleep;Intervention;Knowledge;Light;Link;Longitudinal Studies;Measures;memory consolidation;Methods;Nerve Degeneration;Neurocognitive;neurofilament;Neuronal Plasticity;Neurons;nonalzheimer dementia;Participant;Pathologic;Pathology;Performance;Persons;Phase;Physical Performance;Polysomnography;Population;pre-clinical;prognostication;Proteins;Protocols documentation;Proxy;Quality of life;REM Sleep;Research;Serum;Signal Transduction;Sleep;Sleep Architecture;Sleep Deprivation;Sleep disturbances;sleep pattern;Slow-Wave Sleep;Synapses;tau Proteins;tool;usability;Work

PROJECT_TITLE: Evaluating Sleep Deficiency in Persons with Alzheimer's Disease and Related Dementias


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Human population dynamics and evolutionary history have combined to shape the genomes of people living today, impacting human health, disease susceptibility and our understanding of broader societal and historical questions. We learn about evolutionary processes by studying genetic variation among sequenced individuals, analyses which are grounded in mathematical and statistical innovations. This research will integrate mathematical and empirical approaches to learn key features of our species’ evolutionary history and how that history shapes genetic and phenotypic variation across populations.

PI_NAMEs: RAGSDALE, AARON  (contact)

PROGRAM_OFFICER_NAME: ADKINS, RONALD

PROJECT_TERMS: Address;Admixture;Architecture;Complex;Computing Methodologies;computing resources;Data;Development;Disease susceptibility;diverse data;DNA;Evolution;Genetic;genetic predictors;Genetic Recombination;Genetic study;Genetic Variation;Genome;genome resource;genome sequencing;genomic data;Genomics;Health;Historical Demography;Human;human model;human population genetics;imprint;Individual;innovation;Latin American;Learning;Linkage Disequilibrium;Mathematics;Methodology;Methods;model building;Modeling;Natural Selections;open source;Persons;Phenotype;Polygenic Traits;Population;Population Biology;Population Dynamics;Population Genetics;portability;Process;Recording of previous events;Research;Sample Size;Shapes;simulation;statistics;Structure;theories;trait;Variant;Work

PROJECT_TITLE: Population genetics of human evolutionary history and natural selection

STUDY_SECTION: MRAF

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - F Study Section[MRAF]


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

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Alzheimer's Disease affects about 6 million people in the United States, every minute one American develops Alzheimer’s Disease. APOE4 is the major genetic cause of Alzheimer’s Disease, more than 60% of the patients have one copy of APOE4 yet this genetic knowledge has not been translated to treatment. Leveraging our recent discovery of an enhancer RNA that regulates APOE expression, this project delves into this regulatory relationship and the function of APOE to set the stage for precision Alzheimer's Disease treatment.

PI_NAMEs: CHEUNG, VIVIAN G (contact)

PROGRAM_OFFICER_NAME: BENNANI-BAITI, MICHAEL

PROJECT_TERMS: Address;Affect;Alleles;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer's disease therapeutic;American;Antisense Oligonucleotides;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;Astrocytes;base;Binding;Binding Proteins;biological adaptation to stress;Biological Assay;Cell Physiology;cell type;Cells;Central Nervous System;Chemicals;Coculture Techniques;Complex;cost;cytokine;Data;design;Disease;effective therapy;Enhancers;Exhibits;experimental study;Frequencies;Gene Expression Profile;Gene Expression Profiling;gene therapy;Genes;Genetic;genetic regulatory protein;genetic risk factor;Genetic Transcription;Genotype;Health;Healthcare;Hi-C;Homeostasis;Human;Immunoprecipitation;Individual;inhibitor;insight;Intervention;knock-down;Knowledge;Late Onset Alzheimer Disease;Light;lipidomics;Lipids;Mass Spectrum Analysis;Mediator;Medicine;Microglia;multiple omics;Neurobiology;Neurons;neurotoxicity;Patients;Persons;Play;precision medicine;Precision therapeutics;Predisposition;protein degradation;Proteins;Regulation;Research;response;Risk Factors;RNA;RNA Splicing;RNA vaccine;Role;side effect;Signal Pathway;SMN2 gene;Spinal Muscular Atrophy;Stress;Susceptibility Gene;Synapses;targeted treatment;Therapeutic;therapeutic target;transcription factor;transcriptome sequencing;Translating;United States;Untranslated RNA

PROJECT_TITLE: A comprehensive study of APOE and the noncoding RNA AANCR to advance Alzheimer’s Disease treatment

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Building Research Capacity at Institutions with Limited NIH Funding;Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Neurosciences;Pediatric

ORG_CITY: GREELEY

ORG_NAME: UNIVERSITY OF NORTHERN COLORADO

ORG_STATE: CO

PHR: PROJECT NARRATIVE Our physics and biology collaboration will develop new mathematical and gel-based models of eye morphogenesis, and test the models' predictions against experimental data from zebrafish and other organisms. This work will address a basic research need for quantitative eye morphogenesis models, shed light on the biophysical mechanisms of choroid fissure closure and foveal pit formation, and lay groundwork for future studies aimed at treatment and prevention of colobomas, foveal hypoplasia, and other developmental diseases of the eye. Undergraduate physics and biology majors at the University of Northern Colorado will be involved in all aspects of the proposed research.

PI_NAMEs: ENGSTROM, TYLER  (contact);JAMES, ANDREA E

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: 3-Dimensional;Actins;Address;Basic Science;Behavior;Binding;Biology;biomechanical model;biophysical model;Biophysical Process;Brain;Cadherins;Calculus of Variations;Cell model;Cell Shape;cell type;Cells;Central Nervous System;Cerebellum;Cerebral cortex;Chemicals;Choroid;Clinical Research;Code;Collaborations;Coloboma;Colorado;Computer Simulation;Computers;Coupled;Data;design;Development;developmental disease;Elasticity;elastomeric;Elastomers;Elements;Embryo;Environment;Epithelium;Evolution;Experimental Designs;experimental study;Eye;Eye Development;Eye diseases;Failure;fovea centralis;Future;ganglion cell;Gel;Geometry;Goals;Grant;Growth;Image;indexing;inhibitor;Journals;Knowledge;laboratory experiment;Lead;lissencephaly;Lizards;Manuscripts;Mathematics;mechanical force;Mechanics;Mentors;Mission;model organism;Modeling;Molecular;monolayer;Morphogenesis;Muller's cell;mutant;N-Cadherin;Nature;Neuroepithelial;novel;optic cup;Organism;Output;Photoreceptors;Physics;Postdoctoral Fellow;predictive modeling;Preparation;Prevention;Primates;Process;Publishing;recruit;Regulation;Research;Retina;Running;Series;Shapes;Side;simulation;simulation software;Slice;Solvents;spatiotemporal;Strategic Planning;Students;Supercomputing;Surface;Swelling;symposium;Techniques;Testing;Thick;Time;tissue fixing;Training;Transgenic Organisms;transmission process;undergraduate research experience;undergraduate student;United States National Institutes of Health;Universities;Validation;Variant;Visualization;Work;Zebrafish

PROJECT_TITLE: Developing new biophysical models of choroid fissure closure in zebrafish and foveal pit formation across species

STUDY_SECTION: MABS

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Orphan Drug;Patient Safety;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: PROJECT NARRATIVE The Medical College of Wisconsin hematopoietic cell transplant (MCW HCT) and Cellular Therapy program aims to support the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) as a core center in its mission by leveraging our patient population and faculty expertise in HCT and Cell Therapy for efficient trial conduct in hematologic non-malignant and malignant diseases. In addition, we will build upon our center’s successful development of bispecific chimeric antigen receptor (CAR20.19) T cells as a novel treatment for relapsed B cell malignancies for the treatment of high-risk mantle cell lymphoma. This proposed trial is titled, “Phase II multicenter study of MB-CART2019.1 (zamtocabtagene autoleucel) therapy as frontline consolidation for high- risk Mantle Cell Lymphoma” and is designed specifically to address a priority area of interest identified at the BMT CTN State of the Science meeting in 2021.

PI_NAMEs: SHAH, NIRAV  (contact)

PROJECT_TERMS: 17p;Address;Adherence;anti-CD20;Area;B lymphoid malignancy;B-Cell NonHodgkins Lymphoma;B-Lymphocytes;Blood;Bone Marrow Transplantation;career;career development;CD19 Antigens;CD19 gene;Cell Therapy;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;clinical center;Clinical Data;Clinical Trials;Clinical Trials Network;Collaborations;Complex;curative treatments;Cytogenetics;cytokine release syndrome;Data;Data Collection;Data Coordinating Center;data submission;design;Development;Diagnosis;Disease;Disease remission;Dose;Early treatment;Enrollment;Ensure;equity, diversity, and inclusion;experience;Faculty;first-in-human;follow-up;Funding;gene therapy;gene transplantation for gene therapy;Goals;graft vs host disease;Hematology;Hematopoietic Stem Cell Transplantation;high risk;Histology;Human Resources;immune effector cell-associated neurotoxicity syndrome;improved;improved outcome;In complete remission;Infection;Information Dissemination;innovation;interest;Karyotype;Laboratories;Lead;Leadership;Letters;Link;Lymphoma;Malignant - descriptor;Mantle Cell Lymphoma;manufacture;Medical;medical schools;Medicine;meetings;Mentorship;Mission;mortality;MS4A1 gene;multi-site trial;Multicenter Studies;Mutation;Nature;Newly Diagnosed;next generation;Non-Malignant;novel;novel therapeutics;Observational Study;Outcome;patient population;patient subsets;Patients;Phase;phase 2 study;primary endpoint;primary outcome;prognostic;programs;Progression-Free Survivals;protocol development;Protocols documentation;Publishing;receptor;Receptor Cell;recruit;Recurrent disease;Refractory;Relapse;relapse patients;Reporting;repository;Research Personnel;Residual Neoplasm;Resources;response;Risk;Safety;Science;Scientific Advances and Accomplishments;Scientist;Second Primary Cancers;secondary endpoint;Specimen;standard care;symposium;T cell therapy;T-Lymphocyte;Testing;Therapy trial;Toxic effect;TP53 gene;transplantation therapy;Wisconsin;working group

PROJECT_TITLE: BMT Core- Medical College of Wisconsin


ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE: Endogenous retroviruses (ERVs) are retroviruses that have colonized the germline to become heritable and in rare instances during animal evolution, specific ERV genes have been coopted to perform host functions. Our understanding of ERV biology, and their contributions to human health or disease, have largely been restricted to their nucleic acid sequences as DNA or mRNA. Using a >40-million-year-old, primate-specific, highly potent cell-cell fusogen of unknown function as our model, we will establish methodologies to study the evolution of functional ERV proteins in cells, tissues, and tractable animal systems.

PI_NAMEs: MCCARTHY, KEVIN RAYMOND (contact)

PROJECT_TERMS: Anatomy;Animal Model;Animals;Antibiotic Resistance;Antibodies;B-Lymphocytes;Base Sequence;Biology;Cell Death;Cell fusion;Cell membrane;Cells;Code;Cultured Cells;cytotoxicity;Disease;Distant;DNA;Elements;Endogenous Retroviruses;Evolution;extracellular;Genes;Genetic;Germ Lines;Glycoproteins;Health;Heritability;Human;Human Biology;Human Genome;Immunologist;In Vitro;in vivo;Knowledge;Maternal-Fetal Exchange;Membrane Fusion;Membrane Fusion Activity;Messenger RNA;Methodology;Mitochondria;Modeling;Monkeys;monolayer;nonhuman primate;Organism;Orthologous Gene;Placenta;Pongidae;preservation;Primates;protein expression;Proteins;Proteome;Quality Control;Reagent;receptor;reconstruction;Regulation;Research;Retroviridae;Retrovirus Proteins;Role;Site;Species Specificity;Structure;Syncytiotrophoblast;System;Tissues;tool;Viral;Viral Genes;Virus;Work

PROJECT_TITLE: Hosts Going Viral: Building The Tools And Systems To Determine How Human-Relevant Biology Evolved Through The Capture Of Viral Genes In Our Distant Ancestors

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


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Human Genome;Rare Diseases

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: Project Narrative We identified histone H3K4 demethylases, KDM5A and KDM5B, as dysregulated in context of human and mouse Heart failure (HF). Here, we will define the mechanism and pathogenic contribution and prevention of HF using Gain and loss of function mouse models of these proteins.

PI_NAMEs: GURHA, PRIYATANSH  (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Adult;Age;Age Months;aorta constriction;ATAC-seq;Binding;Biological Assay;Cardiac Myocytes;Cardiomyopathies;cell type;Chromatin;Cleavage Under Targets and Release Using Nuclease;Data;Development;Dilated Cardiomyopathy;DNA Sequence Alteration;Enzymes;Epigenetic Process;Etiology;Family;Fatty Acids;Future;gain of function;Gene Expression;Gene Expression Regulation;Genes;genome-wide;Genomics;Goals;Heart;Heart failure;heart function;Histone Deacetylation;histone demethylase;histone modification;Histones;Human;human model;improved;In Vitro;Individual;induced pluripotent stem cell;Inherited;insight;Investigation;KDM5B gene;Lamins;loss of function;Lysine;Maps;Metabolic;Metabolism;Methylation;Mitochondria;mitochondrial dysfunction;Molecular;Molecular Target;Morbidity - disease rate;mortality;mouse model;Mus;Mutation;Myocardial dysfunction;Oxidative Phosphorylation;Pathogenesis;Pathogenicity;Pathologic;Phenotype;postnatal;pressure;Prevention;Proteins;Research;response;RNA;Role;Sarcomeres;stem;Surgical Models;Syndrome;Testing;Therapeutic;transcriptome sequencing;Withdrawal

PROJECT_TITLE: Roles of Histone lysine demethylases KDM5A and KDM5B in the pathogenesis of Heart failure

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 RCCS-S (02)]


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Genetics

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: Narrative Many increasingly popular study designs in genetic association studies require large-scale hypothesis testing on non-standard hypotheses known as composite null hypotheses. For example, such testing is used to find genetic variants with pleiotropic, mediated, and replicated effects, however the number of validated discoveries remains low relative to the frequency of the investigations. We will develop new methods to perform composite null inference in a robust and interpretable manner, and we will demonstrate the potential of our approaches through application across varied traits.

PI_NAMEs: SUN, RYAN  (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Address;Communities;Complex;Computer software;Data;Data Analyses;Development;Disease;Frequencies;Genetic;genetic analysis;genetic association;Genetic Research;Genetic study;genetic variant;genome-wide;Germ Lines;Goals;high dimensionality;Individual;interest;Investigation;Link;Mediating;Mediation;Mediator;Methodology;Methods;Modeling;Mutation;novel;Outcome;Performance;Phenotype;pleiotropism;Research;Research Design;Research Personnel;Risk;Signal Transduction;simulation;Statistical Methods;Testing;tool;trait;translational genetics;Variant;Work

PROJECT_TITLE: Development of large-scale composite null hypothesis testing approaches to perform translational genetics analyses


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Mental Health;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Although it is widely known that people with opioid use disorder struggle to abstain from opioid use even when receiving evidence-based opioid substitution treatment, the cognitive and neural changes that give rise to reuse risk remain poorly understood. In this project, we use new behavioral, computational, and imaging tools to evaluate the role of a potential modifiable neurocognitive mechanism of reuse risk: unrealistic optimism driving more uncertainty tolerant decision making. Ultimately, our findings have the potential for clear benefits in a clinical setting, providing easily implementable tools to monitor and potentially manage reuse risk, and evaluate clinical status in individual patients.

PI_NAMEs: KONOVA, ANNA BORISOVA (contact)

PROGRAM_OFFICER_NAME: PARIYADATH, VANI

PROJECT_TERMS: Automobile Driving;Behavioral;behavioral study;behavioral tolerance;Chronic;Clinical;Clinical assessments;Cognitive;Complex;computerized tools;Data;Decision Making;Decision Theory;design;Dimensions;evidence base;Exhibits;Functional Magnetic Resonance Imaging;Goals;Health;high risk;Imaging Device;improved;individual patient;Investigation;Life Expectancy;longitudinal design;Measures;Monitor;mortality;Nature;neural;Neurocognitive;novel;novel therapeutic intervention;Opioid;opioid epidemic;Opioid replacement therapy;opioid use;opioid use disorder;optimism;Outcome;patient engagement;Patient-Focused Outcomes;Patients;Persons;Pharmaceutical Preparations;Population;Probability;Process Measure;Psychiatry;Relapse;Resolution;Risk;Role;Testing;tool;Uncertainty;Work

PROJECT_TITLE: Computational psychiatry investigation of the role of unrealistic optimism in opioid use disorder and relapse

STUDY_SECTION: APDA

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


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);Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Dementia;Dietary Supplements;Neurodegenerative;Neurosciences;Nutrition;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: Boulder

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF COLORADO

PHR: PROJECT NARRATIVE The risk of developing mild cognitive impairment, Alzheimer’s disease and related dementias increases with advancing age, largely due to declines in cerebral blood vessel function, which is influenced by age-related increases in mitochondrial oxidative stress. As the aging population is projected to increase in the coming years, establishing effective, preventive strategies to improve cognitive function in older adults by improving cerebrovascular function and decreasing mitochondrial oxidative stress is an urgent biomedical research priority. This administrative supplement will assess the efficacy of a new therapeutic intervention – supplementation with the mitochondrial-targeted antioxidant MitoQ - for improving cognitive and cerebral blood vessel function in older adults and assess the possible mechanism(s) contributing to these benefits.

PI_NAMEs: SEALS, DOUGLAS R (contact)

PROGRAM_OFFICER_NAME: RADZISZEWSKA, BARBARA

PROJECT_TERMS: Acetylcholine;Acute;Administrative Supplement;Aftercare;age effect;age related;Age Years;Aging;aging population;Alternative Therapies;Alzheimer's Disease;Alzheimer's disease related dementia;Antioxidants;Aorta;Award;Biochemical;Biological Availability;Biomedical Research;Blood Flow Velocity;Blood Vessels;brachial artery;brain endothelial cell;Carbon Dioxide;Cell Physiology;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;cerebrovascular reactivity;Cerebrovascular system;Chronic;Clinical;Clinical Trials;Clinical Trials Design;clinically relevant;Cognition;Cognitive;cognitive function;cognitive performance;Crossover Design;Data;Dementia;dementia risk;Dietary Supplementation;Dose;Double-Blind Method;efficacy evaluation;Elderly;Endothelial Cells;Endothelium;Enrollment;executive function;Exposure to;Funding;Goals;Human;Hypercapnia;Impairment;improved;in vivo;Inner mitochondrial membrane;innovation;insight;Internal carotid artery structure;Intervention;Laboratories;Liquid substance;Measures;Mediating;middle cerebral artery;mild cognitive impairment;Mitochondria;Mitochondrial Matrix;Nitric Oxide;novel;novel strategies;novel therapeutic intervention;old mice;older adult;older men;older women;Oral;Oxidative Stress;parent project;Parents;Peripheral;pilot trial;Placebo Control;Placebos;Plasma;Populations at Risk;Positioning Attribute;Prevalence;Prevention strategy;processing speed;Production;Randomized;randomized placebo-controlled clinical trial;Reactive Oxygen Species;Reporting;Research;Research Priority;response;Rest;Risk;Risk Factors;Risk Reduction;Supplementation;Trail Making Test;Translating;Translations;treatment duration;United States National Institutes of Health;Vascular Diseases;vascular endothelial dysfunction;Vascular Endothelium

PROJECT_TITLE: Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Caregiving Research;Clinical Research;Dementia;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Palliative Care;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative The National Health and Aging Trends Study and National Study of Caregiving promote scientific inquiry into late-life disability and Alzheimer's Disease and Related Dementias (ADRD) trends and dynamics, their antecedents and correlates, and disparities therein. The studies are a platform for researchers to engage in scientific inquiry to guide efforts to improve health, functioning, and care for older adults.

PI_NAMEs: FREEDMAN, VICKI A.;SCHRACK, JENNIFER ANN (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, JOHN

PROJECT_TERMS: Accelerometer;Address;Age;age group;Aging;Alzheimer's disease related dementia;Baby Booms;base;beneficiary;Black Populations;Black race;Caregivers;caregiving;Caring;Cognitive;cohort;Collection;Communities;community setting;COVID-19 pandemic;Data;Data Collection;data dissemination;data enclave;Dementia;dementia caregiving;design;Development;diaries;disability;disability risk;Disablement;Disparity;Documentation;end of life;end of life care;Environment;Environmental Risk Factor;ethnic health disparity;Ethnic Origin;experience;Exposure to;falls;Family;Family Caregiver;family caregiving;family support;follow-up;Future;Generations;Geography;Grant;Health;high risk;Hispanic;Hispanic Populations;Hospice Care;human old age (65+);improved;Individual;Inequity;innovation;Internet;Knowledge;late life;Life Cycle Stages;Link;Location;Long-Term Care;Measurement;Measures;Medicare;member;modifiable risk;Movement;multidisciplinary;National Institute on Aging;novel;older adult;Older Population;Palliative Care;Pattern;Persons;Physical activity;Play;Policies;Population;Positioning Attribute;prevent;Procedures;Process;Publications;Quality of Care;Quality of life;Race;racial health disparity;Records;Research;Research Personnel;Residential Treatment;Risk Factors;Role;Sampling;Scientific Inquiry;sedentary lifestyle;Sensory;Services;Shapes;Sleep;sleep pattern;social;Societies;structural determinants;Structure;success;Surveys;Technology;Telephone;trend;United States Centers for Medicare and Medicaid Services;virtual;web site

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-D (M2)]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Food Allergies

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

PHR: NARRATIVE: Mast cells play a critical role in the induction of immune responses, promoting both IgE-dependent allergic responses such as food allergy and non-IgE-mediated inflammatory diseases such as rheumatoid arthritis. Our studies provide a unique opportunity to dissect the mechanisms by which IL-10 modulates mast cell function in the context of both IgE-mediated activation as well as IgE- independent signals such as IL-33 stimulation. These investigations will not only provide key mechanistic insight into the proinflammatory effects of IL-10 on activated mast cells, but also further enhance our understanding of how mast cells promote the development of allergic responses towards better therapeutic approaches.

PI_NAMEs: MATHIAS, CLINTON B (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: Allergens;Allergic;allergic response;Anaphylaxis;Automobile Driving;Cell Lineage;cell mediated immune response;Cell Physiology;cell type;Cells;Connective Tissue;cytokine;Development;Disease;egg;Exhibits;food antigen;Food Hypersensitivity;Goals;Heterogeneity;Homeostasis;IgE;Immune response;immunoregulation;Inflammatory;Inflammatory Response;insight;Interleukin-10;Investigation;Maps;mast cell;mastocytosis;Mediating;Mission;Mucous Membrane;National Institute of Allergy and Infectious Disease;Nature;novel;paracrine;Pathologic;Pathway interactions;Phenotype;Physiological;Play;Population;Production;Proliferating;Regulation;response;Rheumatoid Arthritis;Role;Signal Transduction;Source;Stimulus;Testing;Therapeutic;Therapeutic Intervention;Tissues;transcriptomics

PROJECT_TITLE: Differential regulation of mast cell-mediated allergic responses by IL-10

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(57)]


NIH_SPENDING_CATS: Genetics;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: Narrative This application aims to establish caRNA m5C-MBD6-H2AK119ub deubiquitylation axis as a critical and novel pathway for TET2-mediated HSPC regulation. The proposed studies will gain fundamental knowledge on HSPC biology and lead to novel strategies to target TET2-mutated HSPCs.

PI_NAMEs: HE, CHUAN ;XU, MINGJIANG  (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Adult;Affinity;Animal Model;Antisense Oligonucleotides;base;Binding;Biological;Biological Assay;Biology;CD34 gene;Cells;Chromatin;chromatin protein;Chromosome Mapping;Colony-forming units;Complex;crosslinking and immunoprecipitation sequencing;Data Set;demethylation;DNA;DNA Binding;Gene Expression;gene function;Genetic Transcription;Genomics;granulocyte;Hematopoiesis;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Human;Impairment;Individual;Knock-in;Knock-out;Knowledge;leukemic stem cell;Long Terminal Repeats;LoxP-flanked allele;Mediating;Methods;Methylation;Modification;monocyte;Mouse Embryonic Stem Cells;mouse model;mRNA Stability;Mus;Mutate;Mutation;Myeloproliferative disease;novel;novel strategies;oxidation;Pathway interactions;Physiological;Play;Post-Transcriptional Regulation;Protein Family;Proteins;Proto-Oncogene Protein c-kit;Reader;recruit;Regulation;Resolution;Ribonucleases;RNA;RNA Binding;RNA-Binding Proteins;Role;stem cell function;success;Testing;Transcript;transcriptome sequencing

PROJECT_TITLE: Critical roles of RNA m5C-MBD6-H2AK119ub deubiquitylation axis in TET2-mediated HSC regulation

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


NIH_SPENDING_CATS: Digestive Diseases;Neurosciences

ORG_CITY: PHILADELPHIA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project narrative Memories in the central nervous system are an essential component of human physiology and behavior, but whether memory exists in the peripheral nervous system, and in particular the enteric nervous system, remains unknown. This proposal explores the concept of memory engram formation in enteric neurons. The results of this study have the potential to transform our understanding of how the enteric nervous system contributes to numerous functions and diseases of the gastrointestinal tract, ranging from infection and inflammation to metabolism.

PI_NAMEs: THAISS, CHRISTOPH ALEXANDER (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Address;Animal Model;Antigens;Behavior;Brain;Central Nervous System;Characteristics;dietary;Digestive System Disorders;Disease;Enteral;Enteric Nervous System;Future;gastrointestinal;Gastrointestinal Diseases;Gastrointestinal Physiology;Gastrointestinal tract structure;Goals;Human;Immunology;Infection;Inflammation;insight;Investigation;Knowledge;Learning;lens;life span;Memory;Metabolic Diseases;Metabolism;microbial;Molecular;Nature;neural;Neurons;Neurosciences;novel strategies;Peripheral;Peripheral Nervous System;Physiology;response;Sensory;Stimulus;Systems Biology;tool;Xenobiotics

PROJECT_TITLE: Memory in the enteric nervous system

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-S (M3)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Building Research Capacity at Institutions with Limited NIH Funding;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW ORLEANS

ORG_NAME: XAVIER UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative The proposed research is relevant to public health because it aims to understand processes contributing to high rates of Alzheimer’s disease and related dementias in Black Americans by examining how the neighborhood environment may interact with allostatic load, a biomarker of stress-related physiological dysregulation, to affect cognitive function among midlife and older Black adults. Therefore, this research can inform the design of interventions and policies to target social-environmental and biological risk factors related to adverse cognitive outcomes, including Alzheimer’s disease, specifically among Black Americans. Moreover, the proposed research is relevant to the missions of NIH and NIA of preventing and slowing the development of Alzheimer’s disease and related dementias as well as supporting quality of life among aging Americans.

PI_NAMEs: THIERRY, AMY  (contact)

PROGRAM_OFFICER_NAME: BENSON, RICHARD T

PROJECT_TERMS: Address;Adult;Affect;Age Years;Aging;aging population;allostatic load;Alzheimer's Disease;Alzheimer's disease related dementia;American;Biological;Biological Markers;biopsychosocial;Black American;Black Populations;Black race;Cardiovascular system;caucasian American;Chronic;Chronic stress;Cognitive;cognitive change;cognitive function;Complex;Coupled;Data;Development;Disadvantaged;Disease;Disparity;Economics;Environment;experience;Funding;Future;Growth;Health;Health and Retirement Study;health disparity;High Prevalence;Historically Black Colleges and Universities;Inequality;innovation;Linear Models;Linear Regressions;Louisiana;low socioeconomic status;Mentors;middle age;Mission;Modeling;National Institute on Aging;neighborhood disadvantage;Neighborhoods;older adult;Outcome;Physiological;Policies;Population;population health;Predisposition;Prevalence;prevent;Process;Psychosocial Stress;Public Health;Quality of life;Race;racial diversity;Racial Segregation;Research;Research Personnel;Resources;Risk Factors;Role;Sampling;segregation;Shapes;social;social cohesion;social determinants;social disparities;Socioeconomic Status;socioeconomics;Stress;Stress and Coping;stressor;System;Testing;therapy design;time use;Underrepresented Students;United States National Institutes of Health;Universities

PROJECT_TITLE: Examining the Role of Allostatic Load and Neighborhood Disadvantage in Cognitive Function Trajectories among Midlife and Older Black Americans

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 RCB-T (SB)]


ORG_CITY: STILLWATER

ORG_DEPT: CHEMISTRY

ORG_NAME: OKLAHOMA STATE UNIVERSITY STILLWATER

ORG_STATE: OK

PHR: Project Narrative/Public Health Relevance Statement The ability to rapidly synthesize a diverse array of chemical structures is critical for the discovery and manufacture of new pharmaceuticals. This work aims to provide two enabling technologies, nucleophilic cobalt catalysis and organic single-electron photoreductants, for the rapid and efficient construction of carbon–carbon bonds. The methods enabled by these technologies will provide new tools for practitioners of medicinal chemistry, streamlining drug discovery and development and thereby positively impacting human health.

PI_NAMEs: PITRE, SPENCER  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Alcohols;Alkenes;Anions;base;Carbon;carbonyl compound;Catalysis;catalyst;Chemical Structure;chemical synthesis;Chemicals;Chemistry;Cobalt;Complex;Development;Dihydropyridines;drug development;drug discovery;electron donor;Electrons;functional group;Generations;Halogens;Health;Human;Hydroquinones;Ions;irradiation;manufacture;Mediating;Medicine;Metals;Methods;Organic Chemistry;Organic Synthesis;oxidation;Pharmaceutical Chemistry;Pharmacologic Substance;Process;programs;public health relevance;Reaction;Reducing Agents;Research;Technology;Tin;tool;Visible Radiation;Work

PROJECT_TITLE: Nucleophilic Cobalt Photocatalysis and Organic Single-Electron Photoreductants; Two Enabling Approaches for Chemical Synthesis

STUDY_SECTION: MRAE

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - E Study Section[MRAE]


NIH_SPENDING_CATS: Aging;Building Research Capacity at Institutions with Limited NIH Funding;Genetics;Human Genome;Physical Activity;Prevention;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: WICHITA

ORG_NAME: WICHITA STATE UNIVERSITY

ORG_STATE: KS

PHR: NARRATIVE This project will significantly contribute to our understanding of how exercise interventions impact stem cell aging. By using a multidisciplinary approach, we will uncover the key molecular complement and gene regulatory signatures affected by a conserved cell signaling pathway known for its role to mediate inflammatory responses. Determining how exercise modulates this pathway to render the purported benefits for aging stem cells is critically important for devising intervention strategies to combat aging-induced stem cell impairment.

PI_NAMEs: LOGANATHAN, RAJPRASAD  (contact)

PROGRAM_OFFICER_NAME: CUPIT, PAULINE

PROJECT_TERMS: adult stem cell;Affect;age effect;age related;Aging;aging population;aging related;Animals;Antibodies;Automobile Driving;Biological;Body System;Cardiovascular Diseases;Cell Count;cell injury;Cell model;Cell Physiology;cell type;Cells;Cellular Morphology;Cessation of life;ChIP-seq;Chronic;Chronic disability;Chronic Disease;combat;Complement;Deterioration;Drosophila genus;Dysplasia;effective intervention;endurance exercise;Equilibrium;Evidence based intervention;Exercise;exercise capacity;exercise intervention;exercise training;experimental study;extend lifespan;fitness;functional decline;Functional impairment;functional loss;Gene Expression Profile;Genes;genetic approach;Genetic Complementation Test;Germ Lines;germline stem cells;Goals;Growth;Health;healthcare burden;healthspan;Image;Immunofluorescence Immunologic;Impairment;improved;Individual;Inflammatory Response;insight;interdisciplinary approach;Intervention;Intestines;Janus kinase;Knowledge;Life;life span;lifestyle intervention;Mediating;Mediator;Modeling;Molecular;Morphology;mortality;Natural regeneration;Non-Insulin-Dependent Diabetes Mellitus;novel;Octopamine;Organ;Organism;Osteoporosis;Pathology;Pathway interactions;Phenotype;Physiological;Population;Population Sizes;prevent;Resolution;response;Role;sarcopenia;Signal Pathway;Signal Transduction;single-cell RNA sequencing;stem cell aging;stem cell function;stem cell model;stem cell population;stem cells;System;Testing;Testis;Tissues;Training;Transcriptional Activation;transcriptome;transcriptomic profiling;translational approach;whole genome

PROJECT_TITLE: Impact of Exercise Adaptations on the Aging Stem Cell

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 RCB-T (SF)]


NIH_SPENDING_CATS: Aging;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Interstitial Cystitis;Microbiome;Prevention;Prostate Cancer;Radiation Oncology;Urologic Diseases

ORG_CITY: ROCHESTER

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: NARRATIVE Prostate cancer patients treated by radiotherapy can experience treatment-related toxicities that have life-long negative effects on health-related quality of life. The proposed studies will investigate if the urinary microbiome changes after radiotherapy, and if any changes correlate with the severity of urothelial toxicity after radiotherapy. These questions will be investigated using both banked urine from prostate cancer patients that experienced bladder toxicities after radiotherapy and urine from mouse studies investigating mechanisms of urothelial toxicity, with the long-term goal of using the microbiome as an inexpensive readout of the susceptibility to radiation toxicity.

PI_NAMEs: GILL, STEVEN R.;KERNS, SARAH L.;MARPLES, BRIAN  (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Accident and Emergency department;Acute;Age;Angiotensin-Converting Enzyme Inhibitors;Anti-Inflammatory Agents;Biological Markers;Biological Specimen Banks;Bladder;Bladder Dysfunction;Bladder Injury;bladder trigone;Blood;C57BL/6 Mouse;Cancer Patient;cancer radiation therapy;care costs;Cells;Chronic;Clinical;Clinical Research;clinically relevant;clinically significant;cohort;Collimator;curative treatments;Data;Development;Diagnosis;Dose;Dose Fractionation;dosimetry;dysbiosis;Dysuria;early detection biomarkers;Early treatment;effective therapy;Emergency department visit;experience;extracellular vesicles;follow-up;Frequencies;Functional disorder;Future;gastrointestinal;Genes;Genetic study;Genitourinary system;genome wide association study;Goals;gut microbiome;health related quality of life;Hematuria;Histologic;Human;human old age (65+);human study;Immune;Immune response;Immune system;immunoregulation;Impairment;Incidence;Incontinence;Increased frequency of micturition;Individual;Infection;Inflammation;Inflammatory;Injury;Integration Host Factors;Intervention;Link;longitudinal human study;Malignant neoplasm of prostate;Measures;Mediating;Medical Genetics;men;Metabolic;Metabolism;Metagenomics;Methodology;microbial;microbial community;microbial composition;microbiome;microbiome composition;micturition urgency;Molecular;mouse model;multiple omics;Mus;Natural Killer Cells;older adult;Pain;Pathologic;Pathway interactions;Patient Outcomes Assessments;patient subsets;Patients;Pelvis;Physiological Processes;potential biomarker;pre-clinical;Predisposition;prevent;Prevention strategy;Procedures;Process;prospective;prostate cancer survivors;Prostate Cancer therapy;prostate radiotherapy;protective effect;Quality of life;Radiation;radiation cystitis;radiation mitigator;Radiation therapy;Radiation Tolerance;Radiation Toxicity;Radiation-Induced Cancer;Recording of previous events;recruit;reduce symptoms;response;Ribosomal RNA;Risk;Role;Severities;sex variable;Sexual Dysfunction;side effect;Signal Pathway;Source;Specimen;Symptoms;System;Testing;Time;tissue injury;Tissues;TNFRSF1A gene;Toxic effect;treatment planning;Treatment-related toxicity;urethral microbiome;urinary;Urinary Microbiome;Urinary tract;Urination;Urine;urologic;Urologic Diseases;urothelial injury;Urothelium;Variant;vesicular release;Volatile Fatty Acids;Work

PROJECT_TITLE: The urinary microbiome and bladder toxicity after pelvic radiotherapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-X (M2)]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Precision Medicine;Sleep Research

ORG_CITY: CHICAGO

ORG_DEPT: NEUROLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Delayed Sleep Wake Phase Disorder (DSWPD) is a circadian rhythm sleep-wake disorder characterized by a difficulty in initiating sleep at night and subsequent difficulty in waking at times required for work or school. Several distinct phenotypes of DSWPD have been identified with respect to the timing of circadian and behavioral rhythms, as well as the sensitivity to circadian light signals. This project aims to characterize the physiology and behavior of these subtypes, and using that information, develop targeted physiologically informed diagnostic and treatment strategies for these individuals.

PI_NAMEs: ABBOTT, SABRA M;ZEE, PHYLLIS C. (contact)

PROGRAM_OFFICER_NAME: LAPOSKY, AARON D

PROJECT_TERMS: accurate diagnostics;actigraphy;Acute;Adolescent and Young Adult;Adult;Affect;affective disturbance;alertness;Algorithms;Anxiety;Behavior;Behavior assessment;Behavioral;behavioral phenotyping;Biological Markers;Cardiometabolic Disease;Categories;circadian;Circadian Rhythm Disorder;Circadian Rhythms;Citalopram;Clinical;clinical diagnosis;Clinical Treatment;Clinical Trials;comparison control;Complex;Data;design;Development;diagnostic accuracy;diagnostic criteria;diagnostic strategy;Diagnostic tests;Disease;disorder risk;disorder subtype;Double-Blind Method;Ecological momentary assessment;effective therapy;Enrollment;Environment;Excessive Daytime Sleepiness;Exhibits;falls;Functional disorder;Future;Goals;Health;improved;Individual;individualized medicine;Label;Light;Lighting;mathematical model;Measurement;Measures;Medicine;Melatonin;Mental Depression;Mental Health;Methods;Modeling;Moods;multimodality;Outcome;Participant;Patient Care;Patients;Pattern;Performance;Performance at work;Personal Satisfaction;personalized care;personalized medicine;personalized strategies;Persons;Phase;Phenotype;phenotypic biomarker;Photophobia;physical conditioning;Physiological;Physiology;Placebo Control;Placebos;Population;Predisposition;Prevalence;Prevention;Protocols documentation;Pupil;Pupil light reflex;Quality of life;Questionnaires;Randomized;Reporting;Research;response;Rest;Salivary;Sampling;Schools;Selective Serotonin Reuptake Inhibitor;Signal Transduction;Sleep;sleep quality;stem;suprachiasmatic nucleus;Testing;time use;tool;Treatment Effectiveness;treatment strategy;Work

PROJECT_TITLE: Physiological and Behavioral Basis of Circadian Rhythm Delayed Sleep-Wake Phase Disorder

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Development of medical countermeasures for high-risk chemicals has been limited by several factors, including a lack of standardization among the various experimental models, regulatory constraints faced by individual investigators or small companies, high resource costs to conduct fundamental and translational studies, and a lack of experience in working with highly toxic chemicals. We propose to utilize our established expertise in toxic chemical research to develop a state-of-the-art facility providing analytical and technical expertise to CCRP- supported investigators studying the effects of vesicants and related chemicals in vivo and in vitro using ocular and dermal experimental models, including human microphysiological platforms that increase translational relevance while reducing the need for animal research. It is envisioned this facility will serve as an expert and interactive resource for CCPR-funded investigators to conduct fundamental studies into toxic mechanisms mediating acute injury and chronic injury, as well as early-stage medical countermeasures development.

PI_NAMEs: MCNUTT, PATRICK MICHAEL (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Acceleration;Acute;Administrative Coordination;advanced analytics;Advisory Committees;analytical method;Animal Experimentation;Animals;Autopsy;Businesses;chemical threat;Chemicals;Chronic;Communication;Communities;community engagement;Complement;Complex;Consult;Corneal Injury;cost;Data;Database Management Systems;Dedications;Dermal;Development;Education;empowerment;Ensure;Evaluation;experience;Experimental Models;Eye;Face;Feedback;Fostering;fundamental research;Funding;Genomics;Goals;Grant;Hazardous Chemicals;high risk;Histocytochemistry;Human;improved;In Vitro;in vivo;Individual;Injury;innovation;insight;Institution;Laboratories;Lead;Leadership;Lung;Machine Learning;Marketing;Mediating;medical countermeasure;Methodology;Methods;microphysiology system;Mission;Modeling;multidisciplinary;multiple omics;Mus;new technology;next generation;operation;Oryctolagus cuniculus;Pathway interactions;Phenotype;Physiological;Poison;Pre-Clinical Model;Procedures;Process;programs;Protocols documentation;Public Health;Quality Control;Readiness;real-time images;Regenerative Medicine;Research;Research Design;Research Personnel;Research Support;Resolution;Resources;response;Schedule;Schools;Seasons;Secure;Skin;Standardization;sustainable resource;synergism;Technical Expertise;Techniques;Therapeutic;Thick;Tissues;Toxic effect;Toxicology;Training;Training and Education;translational study;United States National Institutes of Health;Universities;Vesicants;web portal;web site

PROJECT_TITLE: Wake Forest University Vesicant Exposure Resource and Coordination Core

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 LWJ-D (CP)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures


PROJECT_TERMS: 3-Dimensional;Acute;Agreement;Amendment;analytical method;animal care;Animal Experimentation;Animals;appropriate dose;Autopsy;Biochemical;Biomedical Engineering;Budgets;Chemicals;Chronic;Clinical;Collaborations;Communities;Custom;Data;Data Analyses;Data Collection;Doctor of Philosophy;Dose;Education;Ensure;Environmental Health;Equipment and supply inventories;Euthanasia;exposure route;Exposure to;Eye;Funding;Goals;Harvest;high resolution imaging;Histology;Human;human model;Human Resources;improved;In Vitro;in vivo;Injury;innovation;Institution;lipidomics;Liquid substance;medical countermeasure;medical schools;metabolomics;Methods;Microfluidics;microphysiology system;Microscopy;Mitochondria;Modeling;Molecular;Molecular Analysis;molecular marker;Monitor;Mus;operation;Oryctolagus cuniculus;Policies;Procedures;programs;Proteomics;Protocols documentation;recruit;Research Personnel;Research Project Summaries;Research Support;Resources;response;response to injury;Route;Safety;sample collection;Sampling;Schedule;Scientist;Skin;Source;Standardization;Technical Expertise;Testing;Thick;Time;time use;tissue injury;Tissues;Training;transcriptomics;United States National Institutes of Health;Universities;vapor;Vesicants;Veterinary Medicine;Visit;Work


PROJECT_TERMS: Animals;base;Calendar;Communication;Communities;community engagement;Computer software;Data;data exchange;Dedications;Doctor of Philosophy;Educational Materials;Ensure;Environment;Equipment;Event;experimental study;Funding;High Performance Computing;Human Resources;IACUC;improved;Industry;Information Technology;interest;Journals;Leadership;Link;Location;Marketing;Measures;member;Methodology;news;Notification;operation;Play;programs;Protocols documentation;Publications;Quality Control;Recommendation;recruit;Reporting;Research;Research Personnel;Resources;Role;satisfaction;Schedule;Scientist;Secure;Services;Standardization;Technical Expertise;tool;Training;United States National Institutes of Health;Universities;Update;usability;Vesicants;web portal;web site;Work


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Hypertension;Nutrition;Obesity;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: GREENSBORO

ORG_NAME: NORTH CAROLINA AGRI & TECH ST UNIV

PHR: The overarching goal is to identify opportunities for interventions to decrease HBP risk in BD1As. To accomplish this task, we must evaluate 1) whether the association between LEA and CVD risk from our lab is credible, 2) determine its strength with an appropriate population sample, and 3) whether SDOH moderates this association.

PI_NAMEs: PURDOM, TROY  (contact)

PROGRAM_OFFICER_NAME: BROWN, ALISON GWENDOLYN MARY

PROJECT_TERMS: Address;Affect;aged;Aging;Aorta;Area;arterial stiffness;Arteries;Athletic;Awareness;Biological Markers;Black race;Blood Vessels;built environment;Calories;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;Carotid Arteries;cationic antimicrobial protein CAP 37;Cause of Death;cohort;college;Communities;Consumption;Data;Diet;Discrimination;Eating Disorders;Economics;Education;energy balance;Energy Metabolism;Equity;evidence base;experience;Exposure to;Fatty acid glycerol esters;Female;femoral artery;Femur;Food;food security;Fruit;Functional disorder;Goals;Gold;Health;health literacy;high risk;Hypertension;indexing;instrument;Intake;International;Intervention;Knowledge;Linear Models;Link;Literature;Longitudinal, observational study;male;Malnutrition;Measurable;Measures;Minority;Modeling;multidisciplinary;Nonpharmacologic Therapy;novel;novel strategies;Nutrient;nutrition;Nutritional;Outcome;Participant;Physiologic pulse;Physiological;Population;pressure;Processed Meats;Publishing;Questionnaires;recruit;Research;Risk;Sampling;Seasons;skills;social;social health determinants;Sports;sports related nutrition;sudden cardiac death;sugar;sweetened beverage;Testing;transmission process;Vegetables;Work

PROJECT_TITLE: Low Energy Availability (LEA), Nutritional Deficiencies and Hypertension in Black Division I Athletes


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Down Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: PROJECT NARRATIVE People with Down syndrome are disproportionally impacted by Alzheimer’s disease as they age , and current research indicates that TREM2, which is a protein that is expressed in microglial cells in the brain, plays a critical role in the development of Alzheimer’s disease in both this population as well as others without Down syndrome. In this project, we propose to study MS4A molecules-mediated regulation of TREM2 and microglial activation in mouse models of Alzheimer’s disease in Down syndrome by using CRISPR-based genome engineering. Success of this project will significantly enhance our understanding of the molecular processes underlying Alzheimer’s disease in Down syndrome and potentially lead to the identification of novel therapeutic targets, which may hold promise for treating all people suffering fromAlzheimer’s disease.

PI_NAMEs: YU, EUGENE  (contact)

PROGRAM_OFFICER_NAME: PARISI, MELISSA

PROJECT_TERMS: abeta oligomer;Achievement;Affect;Age;Age Years;Alleles;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease patient;Amyloid Beta A4 Precursor Protein;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Animal Model;Applications Grants;Area;Binding;Brain;brain tissue;Breeding;burden of illness;Cell Physiology;Cerebrospinal Fluid;Characteristics;Chromosomes;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Cognitive deficits;Complex;CRISPR/Cas technology;Data;Dementia;Development;Diagnosis;Disease;Down's Syndrome;effective therapy;Engineering;Event;Evolution;experimental study;Family member;Fluorescent in Situ Hybridization;Gene Cluster;Gene Duplication;Gene Family;General Population;Generations;Genes;Genetic;Genome engineering;genome wide association study;Genomic Segment;Genotype;glial activation;Goals;Human;in vivo;Individual;Innate Immune Response;innovation;Integral Membrane Protein;Intervention;Knock-out;Knockout Mice;Knowledge;L Cells;Masks;Measurement;Mediating;Medical;member;Methods;Microglia;Molecular;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;neuropathology;neurotoxicity;new therapeutic target;Pathogenesis;Pathologic;Patients;Pattern recognition receptor;Persons;Phenotype;Play;Population;Process;Proteins;Regulation;Research;Research Project Grants;Role;success;targeted treatment;Technology;Testing;therapeutic target;time use;TREM2 gene

PROJECT_TITLE: Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits

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


ORG_CITY: KNOXVILLE

ORG_NAME: UNIVERSITY OF TENNESSEE KNOXVILLE

ORG_STATE: TN

PHR: PROJECT NARRATIVE Neutrophils play a crucial role in establishing innate immunity and must metabolically adapt to persist and perform the inflammatory functions across a variety of metabolic environments during bacterial septicemia. This proposal investigates how neutrophils leverage their mitochondria to sense metabolic disruptions during infection and applies cutting-edge technology to unbiasedly identify alternative metabolic pathways influencing modifications to the epigenome, gene transcription, and inflammatory processes during sepsis. The fundamental insights into the interplay between metabolism and inflammation discerned by this proposal is ideally suited for the Maximizing Investigators’ Research Award and will establish a scientific and technological foundation to expand into novel metabolic pathways, other innate immune cells, and alternative inflammatory diseases.

PI_NAMEs: MONTEITH, ANDREW J (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TITLE: Defining the mitochondrial metabolic regulation of systemic innate inflammation

STUDY_SECTION: MRAD

STUDY_SECTION_NAME: Maximizing Investigators' Research Award - D Study Section[MRAD]


NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Human

ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: NARRATIVE This proposal seeks to enhance our understanding of cell-specific protein quality control in the endoplasmic reticulum (ER). It outlines three goals: establishing the principles governing selection for ERAD and ER-phagy systems, defining the mechanisms by which glycan site occupancy regulates ER quality control, and understanding cell-type specific ER-phagy. By utilizing isogenic induced pluripotent stem cell (iPSC) derived hepatocytes and neurons, the research aims to shed light on complex protein homeostasis processes, potentially leading to new therapies for protein misfolding disorders.

PI_NAMEs: SCHULTZ, MARK LOUIS (contact)

PROGRAM_OFFICER_NAME: PHILLIPS, ANDRE W

PROJECT_TERMS: Address;alpha 1-Antitrypsin Deficiency;Autophagocytosis;Biochemical;cell type;Cells;Cystic Fibrosis;Deficiency Diseases;Disease;disease-causing mutation;Endoplasmic Reticulum;excitatory neuron;Gaucher Disease;gene product;Goals;Hepatocyte;Human;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;insight;Isoleucine;Lentivirus;Lysosomes;Methods;multicatalytic endopeptidase complex;Mus;mutant;Neurons;novel;novel therapeutics;NPC1 gene;Pathway interactions;Play;polypeptide;Polysaccharides;Positioning Attribute;Process;protein complex;protein misfolding;Proteins;Proteome;proteostasis;Quality Control;receptor;Regulation;Research;Role;Site;small molecule;small molecule inhibitor;Structure;System;Threonine;Variant

PROJECT_TITLE: Regulation and Mechanisms of ER Proteostasis