ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Biomedical Imaging;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Lung;Lymphatic Research;Neurosciences

PHR: Project Narrative:  Cerebrospinal fluid flow is critical for maintaining brain health and clearing metabolic waste products from the brain. Both respiration and neural activity are thought to play a role in driving CSF flow. This project will test the role of both respiratory and noninvasive neurostimulation interventions in regulating CSF flow, laying the foundation for future clinical studies seeking to test therapeutic impact of altering CSF flow in clinical populations.

PI_NAMEs: LEWIS, LAURA DIANE (contact)

PROGRAM_OFFICER_NAME: BELFER, INNA

PROJECT_TERMS: afferent nerve;Alzheimer's Disease;Arousal;Automobile Driving;blood oxygen level dependent;Blood Vessels;Brain;brain health;Brain Stem;Breathing;Cell Nucleus;Cerebrospinal Fluid;cerebrospinal fluid flow;Clinical;clinical investigation;Clinical Research;Coupled;Coupling;design;Failure;fluid flow;Foundations;Frequencies;Functional Magnetic Resonance Imaging;Future;glymphatic clearance;glymphatic system;hemodynamics;Human;Image;Imaging Techniques;improved;Intervention;Link;locus ceruleus structure;Maps;Measurement;Measures;Mediating;Metabolic;Nerve;neural;neural stimulation;Neurodegenerative Disorders;Neurodevelopmental Disorder;neuroimaging;neuroregulation;noradrenergic;Outcome;Patient-Focused Outcomes;Periodicity;Physiology;Play;Population;Process;Resolution;Respiration;respiratory;Rest;Role;Signal Transduction;spatiotemporal;Techniques;temporal measurement;Testing;therapeutic evaluation;Tissues;Transcutaneous Electric Nerve Stimulation;vagus nerve stimulation;Wakefulness;Waste Products;wasting;Work

PROJECT_TITLE: Neuroimaging the impact of respiration and respiratory-gated neuromodulation on human glymphatic physiology


ADMINISTERING_IC: MD

ARRA_FUNDED: N

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Cervical Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Precision Medicine;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Sexually Transmitted Infections;Social Determinants of Health;Women's Health Research

ORG_CITY: SAN JUAN

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: LIFEGENE-BIOMARKS, INC.

ORG_STATE: PR

PHR: Narrative  The goal of this project is to demonstrate the feasibility for the commercialization of the CervicalMethDx Test, a precision methylation test in self-collected samples to stratify Latina women for high risk of cervical  cancer. Latinas have the highest cervical cancer prevalence and incidence rates in United States and Puerto  Rico. A highly sensitive and specific risk test on self-collected samples will enable a novel precision  medicine paradigm, enabling a reduction in cervical cancer disparities in US and ex-US communities.

PI_NAMEs: GUERRERO-PRESTON, RAFAEL  (contact)

PROGRAM_OFFICER_NAME: WHITE, DOLLY PENN

PROJECT_TERMS: Abate;Acetic Acids;advanced disease;aged;Algorithms;biomarker development;Blinded;cancer health disparity;Cervical;Cervical Cancer Screening;Cervical Intraepithelial Neoplasia;Clinical;clinical risk;cohort;Colorectal Cancer;commercialization;Communities;Complex;cost;Country;Cytology;Disease;Disparity;DNA Markers;DNA Methylation;DNA Sequence;Enrollment;Epigenetic Process;ethnic diversity;Ethnic Origin;Evaluation;feasibility testing;Federally Qualified Health Center;Fright;Future;Goals;Guidelines;Health;Health Insurance;Health Promotion;high risk;High Risk Woman;HPV positive;HPV-High Risk;Human papilloma virus infection;Human Papillomavirus;Incidence;Income;Insurance Coverage;intraepithelial;Knowledge;Laboratories;Laboratory Research;Language;Latina;Latina Population;Left;Lesion;Low income;low income country;Low Income Population;Malignant Breast Neoplasm;Malignant neoplasm of cervix uteri;Malignant Neoplasms;Medicaid;Medical;medical schools;Methylation;methylation testing;Montana;mortality;multiplex assay;novel;Oncogenic;Pap smear;Patients;Perception;Performance;personalized screening;Phase;phase 1 testing;Policies;precision medicine;Predictive Value;premalignant;Prevalence;prevent;Preventive;Privatization;programs;Prospective Studies;Puerto Rico;Race;Retrospective Studies;Risk;Sampling;screening;Screening for cancer;screening guidelines;Services;Small Business Innovation Research Grant;social health determinants;Specificity;Squamous intraepithelial lesion;Swab;Technology;Testing;Time;tool;Transportation;treatment guidelines;trial comparing;tumor;Uninsured;United States;United States Preventative Services Task Force;Universities;Vagina;Validation;Viral;Visit;Visual;White Women;Woman;World Health Organization

PROJECT_TITLE: Precision screening in self-collected samples to reduce cervical cancer disparities among Latinas

STUDY_SECTION_NAME: Special Emphasis Panel[ZMD1 JT (A1)]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE In the partnership between UCSF and OncoVision, this project aims to improve the quantification of serial imaging with dedicated breast positron emission tomography (dbPET) and to assess whether dbPET (or in combination with magnetic resonance imaging (MRI)) can effectively predict early treatment response in breast cancer.

PI_NAMEs: ALAMO, JORGE ;HYLTON-WATSON, NOLA M. (contact);ONISHI YAMASHITA, NATSUKO

PROGRAM_OFFICER_NAME: KIM, BOKLYE

PROJECT_TERMS: Adjuvant Chemotherapy;Adopted;Aftercare;Algorithms;attenuation;biological heterogeneity;biomarker performance;Blood Vessels;Breast;Breast Diseases;Breast Magnetic Resonance Imaging;cancer biomarkers;Cancer Burden;Cancer Center;cancer subtypes;Characteristics;chemotherapy;Clinical;Clinical Management;Clinical Trials Design;Companions;Computer software;contrast enhanced;cost;cost effective;cytotoxicity;Data;Dedications;Development;Disease;Dose;Early treatment;effective intervention;effective therapy;Enrollment;Evaluation;experience;Genomics;Goals;Image;Image Analysis;image processing;image registration;imaging biomarker;improved;In complete remission;in vivo imaging system;Industrialization;industry partner;interest;Intervention;Investigation;Lead;Lesion;Logistic Regressions;Magnetic Resonance Imaging;Malignant Breast Neoplasm;Malignant Neoplasms;Mammography;Maps;Measurement;Metabolic;Molecular;Monitor;Morphology;Neoadjuvant Therapy;Nonmetastatic;novel;novel therapeutics;Outcome;Output;participant enrollment;Pathologic;Patients;Performance;performance tests;Phase II Clinical Trials;Positioning Attribute;Positron-Emission Tomography;predicting response;Prediction of Response to Therapy;predictive modeling;prognostic value;Prospective Studies;radiologist;radiomics;radiotracer;research clinical testing;Research Personnel;Residual Cancers;Resolution;response;Role;Scanning;Selection for Treatments;serial imaging;Signal Transduction;software development;Software Tools;Standardization;System;Technology;Testing;Texture;Time;tool;Tracer;Translating;Translations;treatment response;tumor;Tumor Biology;tumor metabolism;Tumor Volume;uptake;user-friendly;Work

PROJECT_TITLE: Dedicated breast PET and MRI for characterization of breast cancer and its response to therapy


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Brain Disorders;Epilepsy;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences

ORG_CITY: BALTIMORE

ORG_NAME: EPIWATCH, INC.

ORG_STATE: MD

PHR: PROJECT NARRATIVE Uncontrolled epilepsy affects over 1.5 million Americans and is characterized by recurrent seizures that impact physical and mental well-being. These impacts can be mitigated by continuous seizure monitoring with wearable devices, but while most wearable seizure monitoring has focused on generalized tonic-clonic seizures, here we propose a new paradigm for focal seizure monitoring using commonly available biosensors on a popular consumer wearable device. Successful development and validation will significantly improve the lives of patients, caregivers and physicians by promoting independence, peace-of-mind, and better epilepsy control.

PI_NAMEs: CRONE, NATHAN E (contact)

PROGRAM_OFFICER_NAME: FORBES, JESSICA CARLENE

PROJECT_TERMS: Accelerometer;Affect;algorithm development;Algorithms;American;Apple watch;Attention;Automatism;Behavior;Biosensor;Bypass;Cardiac;Caregivers;Cessation of life;Characteristics;Classification;Classification Scheme;Clinical;commercialization;Computer software;Controlled Clinical Trials;Data;Data Set;deep learning model;Detection;detector;Development;Devices;diaries;digital health;Direct Costs;Electroencephalography;Epilepsy;experience;Financial Hardship;Focal Seizure;Future;Goals;Health;high risk;Hour;Impact Seizures;improved;Individual;individual patient;Injury;Institutional Review Boards;Legal patent;Machine Learning;Manuals;Methodology;Methods;Mind;Modeling;Monitor;Motor;Movement;Observational Study;patient variability;Patients;peace;Performance;Persons;Phase;Photoplethysmography;Physicians;Positioning Attribute;Procedures;prospective;Psyche structure;Public Health;Quality of life;Recurrence;Research;Safety;Seizures;sensor;social stigma;Stereotyping;stereotypy;Stigmatization;Technical Expertise;Technology;Testing;Time;Tonic - clonic seizures;tool;Training;transfer learning;Validation;Variant;wearable device;Well in self;Work

PROJECT_TITLE: Focal seizure monitoring with a consumer wearable: algorithmic development and validation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ETTN-C (10)]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Burden of Illness;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Hematology;Palliative Care;Patient Safety;Regenerative Medicine;Rehabilitation;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: DURHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Home-based hematopoietic stem cell transplant (home HCT) has the potential to improve patient health, quality of life, and function as well as caregiver well-being outcomes by bringing hospital-level care and resources to the home setting, simplifying logistics for caregivers while also providing intensive support tailored to individual patient and caregiver needs at home. Although increased staffing will be needed upfront, overall costs and resource utilization may be reduced by keeping patients at home.

PI_NAMEs: SUNG, ANTHONY  (contact)

PROGRAM_OFFICER_NAME: NELLISSERY, MAGGIE JACOB

PROJECT_TERMS: Ambulatory Care Facilities;Anecdotes;Antibiotics;Anxiety;arm;Autologous;Back;Blood Transfusion;Cancer Patient;Caregiver Burden;caregiver quality of life;caregiver strain;Caregiver support;Caregiver well-being;Caregivers;Caring;clinical practice;cognitive function;cost;Crowding;Deterioration;Disease;Disease remission;efficacy evaluation;Emergency department visit;Emotional;empowerment;Environment;experience;Family;Fatigue;Financial Hardship;financial toxicity;Food;Future;Geographic Locations;Health;Health Care Costs;health care service utilization;Health Expenditures;Health Personnel;Health system;Hematopoietic Stem Cell Transplantation;Home;Home environment;Home visitation;hospital bed;hospital readmission;Hospitalization;Hospitals;improved;improved outcome;indexing;individual patient;individualized medicine;innovation;insight;Institution;integrated care;Intervention;Interview;Intravenous;Length of Stay;Logistics;Malignant Neoplasms;Managed Care;Measures;Mediating;Mental Depression;Mental Health;Modeling;National Center for Advancing Translational Sciences;Neighborhoods;novel strategies;nutrition;Nutritional status;older adult;Outcome;Patient Care;patient home care;Patient-Focused Outcomes;Patients;Phase;phase II trial;phase III trial;Physical Function;Population;primary endpoint;programs;Provider;Quality of Care;Quality of life;Randomized;Reporting;Resources;safety and feasibility;satisfaction;Self Efficacy;Sleep;Social support;Stress;success;Suggestion;Symptoms;Testing;Transplant Recipients;Transplantation;Travel;treatment planning;Uninsured Medical Expense;Visit;Walking;Work

PROJECT_TITLE: Home-based Autologous Hematopoietic Stem Cell Transplantation to Improve Outcomes and Decrease Costs

STUDY_SECTION: NRCS

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Narrative The study is to evaluate a newly developed mucosal adjuvant for its ability to augment influenza vaccines in the elderly. Despite wide-spread vaccination programs, influenza-related complications in the elderly remain a major public health concern because the current vaccines are not effective in the over 65 population. The new adjuvant can address this unmet medical need specifically.

PI_NAMEs: WU, MEI X (contact)

PROGRAM_OFFICER_NAME: GORDON, JENNIFER L

PROJECT_TERMS: Address;Adjuvant;Adjuvanticity;Age;aged;Aging;aging population;Agonist;Air;alveolar epithelium;Alveolar Macrophages;Alveolus;Antigen Targeting;Antigen-Presenting Cells;Attenuated;Biological Response Modifiers;Biomimetics;Cause of Death;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Aging;Cells;Cellular Immunity;Cessation of life;Clinical;cost;COVID-19;COVID-19 pandemic;cross immunity;Cyclic GMP;Cytosol;Death Rate;Defect;Dendritic Cells;Disease;Distant;Effectiveness;Elderly;Encapsulated;Endocytosis;Engineering;Epithelial Attachment;Epithelial Cells;Excision;Face;Ferrets;flu;Gene Activation;Genes;H1N1 vaccine;Health;Healthcare Systems;Hospitalization;Humoral Immunities;Immune;Immune response;Immune system;Immunity;Immunization;Immunization Programs;immunopathology;improved;Infection;Inflammaging;Inflammation;Influenza;Influenza A Virus, H1N1 Subtype;Influenza A Virus, H3N2 Subtype;Influenza A Virus, H7N9 Subtype;Influenza vaccination;influenza virus vaccine;Inhalation;interest;Interferons;Invaded;ITGAM gene;Learning;Liposomes;Longevity;Lung;Mediating;Medical;Membrane;Memory;memory CD4 T lymphocyte;Middle East Respiratory Syndrome;Modeling;Monitor;Mucous Membrane;Mus;Names;Nature;novel;old mice;Organ;particle;Persons;Phospholipase A2;Play;Population;Predisposition;prevent;Production;Public Health;Pulmonary Surfactant-Associated Protein A;Pulmonary Surfactants;recruit;respiratory;Respiratory System;response;Role;Science;Severe Acute Respiratory Syndrome;Single Nucleotide Polymorphism;Structure of parenchyma of lung;T-Lymphocyte;tissue resident memory T cell;Tissues;Tsunami;universal influenza vaccine;Vaccination;vaccination strategy;Vaccines;Viral Respiratory Tract Infection;Viral Vaccines;Virus;Virus Diseases;young adult

PROJECT_TITLE: A new mucosal adjuvant for augmenting influenza vaccines in elderly

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: PHILADELPHIA

ORG_NAME: PHILADELPHIA VA MEDICAL CENTER

ORG_STATE: PA

PHR: This program of research using a mixed methods approach will reveal new insights into what matters most to Veterans discharged to post-acute care, and how best to align care with their values and goals. With the aging Veteran population and rising costs of care, the VA will need robust evaluation of Veteran priorities and outcomes across post-acute care settings to inform policy decisions. Choice of post-acute care type may be one of the highest-points to influence value and improve Veteran-relevant outcomes– given if individuals are unable to recover, they frequently go on to long-term care at an extraordinary expense to themselves and the VA. However, Veterans values and priorities for post-acute care are unknown, and our approach will establish important patient-centered outcomes for the VA to consider in achieving high-value post-acute care.

PI_NAMEs: MANGES, KIRSTIN ANNE (contact)

PROJECT_TERMS: acceptability and feasibility;acute care;Address;Aging;black patient;care costs;care delivery;care preference;care systems;career;Caregiver Burden;Caregivers;Caring;Categories;Climacteric;Clinical;cohort;Communities;Complex;Data;Data Set;Death Rate;Decision Making;Development;Disadvantaged;Ensure;ethnic disparity;Evaluation;Evidence based practice;Face;falls;Family;functional improvement;Goals;health goals;Healthcare;high risk;Home;Home Care Services;Home Health Agency;hospital readmission;Hospitalization;Hospitals;implementation outcomes;improved;Individual;Injury;innovation;Inpatients;insight;Interview;Knowledge;large datasets;Lead;Life;Light;Literature;Long-Term Care;Measurable;Measures;Medical Care Team;Medicare;Methodology;Methods;military veteran;mortality;novel;Nursing Homes;Outcome;patient oriented;Patient-Focused Outcomes;Patients;Policies;Policy Maker;preference;Preparation;pressure;programs;Provider;Quality of life;racial disparity;readmission rates;Recording of previous events;Recovery;Replacement Arthroplasty;Reporting;Research;Research Personnel;Sampling;Science;Services;Skilled Nursing Facilities;skills;Sorting;support tools;Techniques;Testing;Time;tool;Training;user centered design;Veterans;web site;Work

PROJECT_TITLE: Aligning Post-Acute Care with Veterans Values and Priorities

STUDY_SECTION_NAME: Research Career Scientist[MRA0]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: DUBLIN

ORG_COUNTRY: IRELAND

ORG_FIPS: EI

ORG_NAME: TRINITY COLLEGE DUBLIN

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

PI_NAMEs: CORVIN, AIDEN PETER (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

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

PROJECT_TITLE: 6/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact

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


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Nanotechnology;Prostate Cancer;Urologic Diseases

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: We propose to develop a novel theranostic formulation of nanoparticles that accumulates in prostate cancer cells through a specific chemical reaction initiated by the tumor-specific enzyme legumain. The formulation consists of self-assembled olsalazine molecules that can provide contrast on MRI scans and simultaneously inhibits cell division, which allows us to see if the tumor takes up the drug and if this uptake leads to inhibition of tumor growth. This is important, as we may then be able to predict early on if the tumor will eventually respond to treatment.

PI_NAMEs: BULTE, JEFF W. (contact)

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: Affect;Anti-Inflammatory Agents;Antineoplastic Agents;Arginine;asparaginylendopeptidase;Aspirin;Biodistribution;biomaterial compatibility;Blood;cancer cell;cancer imaging;Caspase;Cell division;Cell membrane;Cells;Cellular Membrane;Chemical Agents;chemical reaction;Chemicals;clinical translation;clinically relevant;Colon Carcinoma;contrast enhanced;Contrast Media;Data;Detection;DNA Methylation;DNA Methylation Inhibition;Drug Efflux;Drug Exposure;Drug resistance;DU145;efflux pump;Enzymes;Failure;FDA approved;Formulation;Glutathione;Goals;Hour;Human;Hydroxyl Radical;Image;Image Enhancement;imaging biomarker;imaging platform;In Vitro;in vivo;inhibitor;Injectable;Intravenous;Kidney;Label;Length;Liver;LNCaP;Magnetic Resonance Imaging;Malignant - descriptor;Malignant neoplasm of prostate;Malignant Neoplasms;Measurement;Measures;Mediating;Membrane Proteins;Modeling;Modification;mouse model;MRI Scans;Mus;nanoformulation;nanoparticle;Nanostructures;nanotheranostics;near infrared dye;Near-infrared optical imaging;neoplastic cell;novel;novel anticancer drug;Optics;Organ;overexpression;Penetration;Peptides;Permeability;Pharmaceutical Preparations;pharmacologic;Physical condensation;Prediction of Response to Therapy;prognostic;Property;Proprotein Convertases;Prostate;prostate cancer cell;prostate cancer cell line;prostate cancer model;Prostate Cancer therapy;protein aminoacid sequence;Protons;Reaction;Salicylic Acids;self assembly;Signal Transduction;single molecule;small molecule;Spleen;subcutaneous;success;Testing;theranostics;Therapeutic;Time;Toxic effect;transgenic adenocarcinoma of mouse prostate;Transgenic Mice;Treatment Efficacy;treatment response;tumor;tumor growth;tumor initiation;uptake;Validation;Visualization;Xenograft Model

PROJECT_TITLE: Intracellular Self-Assembly of Theranostic Nanoparticles for Enhanced Imaging and Tumor Therapy

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: KANSAS CITY

ORG_NAME: UNIVERSITY OF MISSOURI KANSAS CITY

ORG_STATE: MO

PHR: Project Narrative Nearly 100 million people in the US suffer from at least one neurological disease, many of which arise from perturbations in neuronal differentiation and/or circuit formation. Our research leverages the powerful Drosophila genetic model system to uncover the cellular, developmental, and genetic basis of neuronal differentiation, neural circuit formation, and behavior. Given the highly conserved nature of nervous system development from flies to humans, our work holds significant promise to inform on the cellular, developmental, and genetic basis of neurological diseases in humans.

PI_NAMEs: LACIN, HALUK  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Achievement;Adopted;Adult;Animal Behavior;Axon;Behavior;Behavior Control;Biological Models;Cell Physiology;Complex;Dendrites;Development;Diffuse Pattern;Dissection;Drosophila genus;embryonic stem cell;Exhibits;fly;Flying body movement;gene function;Genes;Genetic;Genetic Models;Goals;Grooming;homeodomain;Human;Impairment;Individual;Knee;Knowledge;Label;Leg;Libraries;Link;Maps;Molecular;Morphology;Motor Neurons;Movement;mutant;Nature;Nerve;Nervous System;nervous system development;Nervous System Disorder;neural circuit;neuronal circuitry;Neuronal Differentiation;neuronal patterning;Neurons;Neuropil;Neurotransmitters;optogenetics;Pathway interactions;Pattern;Persons;Play;POU Domain;Proteins;Reflex action;Regulatory Pathway;Research;response;Role;Spinal Cord;Stereotyping;Structure;Synapses;System;tool;transcription factor;transcription regulatory network;Vertebrates;Walking;Wing;Work

PROJECT_TITLE: Developmental and Genetic Basis of Neural Circuit Formation and Behavior

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR]


ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Viruses can attack their human hosts in various ways—sometimes causing a rapid onset of symptoms, as in the case with the Ebola virus, which causes disease by causing apoptosis in many different host cells; other viruses, such as HIV, are characterized by a slow onset of symptoms and long-term persistence, with disease becoming apparent only after months or even years as they modify hosts cells to resist natural cell death pathways, becoming “virus factories,” which produce high levels of virus for extended periods of time. Our goal, to repress these cell death resistance mechanisms in HIV-infected cells, will allow the present viral proteins to trigger HIV-infected cell death and eradicate HIV from the infected patient and cure the HIV infection. Successful completion of the aims of this grant will benefit not only those cured of HIV, but will also reduce the spread of HIV infection, decrease the frequency of HIV resistance, and reduce the complications of living with HIV and HIV therapies.

PI_NAMEs: BADLEY, ANDREW D (contact)

PROGRAM_OFFICER_NAME: LACOURCIERE, GERARD

PROJECT_TERMS: AIDS prevention;antagonist;Anti-Retroviral Agents;antiretroviral therapy;Apoptosis;Apoptotic;Archives;bak protein;BCL-2 Protein;Binding;BLT mice;Bortezomib;Cause of Death;CD4 Positive T Lymphocytes;Cell Death;Cell Death Induction;cell killing;Cell Physiology;cell type;Cells;Cessation of life;Characteristics;Chronic;clinic ready;Clinical;Clinical Trials;clinically relevant;Complex;Cytosol;Data;Diagnosis;Disease;Drug resistance;Ebola virus;Environment;FDA approved;Frequencies;Funding;Genetic Polymorphism;Genetic Transcription;Genotype;Goals;Grant;Helper-Inducer T-Lymphocyte;Heterogeneity;HIV;HIV Infections;HIV Protease;HIV resistance;HIV therapy;Human;Immune;Immune response;immunodeficiency;in vivo;Induction of Apoptosis;Infection;Infectious Agent;inhibitor;insight;Ionizing radiation;Laboratories;Ligation;Lymphoid;Lymphoid Tissue;Measures;memory CD4 T lymphocyte;Modeling;multicatalytic endopeptidase complex;novel;Obstruction;Pathway interactions;Patients;peripheral blood;permissiveness;Persons;pharmacologic;Phenotype;Predisposition;Prevalence;Prevention;pro-apoptotic protein;Proteasome Inhibitor;Proteins;Publishing;Puma;Regulation;Repression;Resistance;resistance mechanism;Respondent;responders and non-responders;response;Shock;Signal Transduction;Stimulus;success;Symptoms;T memory cell;T-Lymphocyte;Testing;Time;Toxic effect;TP53 gene;transmission process;treatment optimization;Up-Regulation;Vaccines;Viral;Viral Proteins;Virus

PROJECT_TITLE: Prime shock and kill for HIV erradication

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

PHR: My research is focused on predictive modeling, quality measurement and management, and implementation and de-implementation science. I will use the research career scientist (RCS) award to extend my programs of research in three high-impact areas. First, many health conditions have several competing treatment options but clinicians and patients do not have accurate information about which patients are most likely to benefit from which treatments. To realize the promise of “precision medicine”, accurate patient-specific prediction models need to be developed, validated, and methods to integrate the predictions into informed consent and shared decision-making need to be tested. Second, research on the effects of healthcare quality measurement is essential to ensure that our systems of accountability are having the intended effects. Finally, designing and testing strategies to get healthcare systems to provide higher quality care and to stop providing care that is unsafe, ineffective, or low value represents an enduring scientific and organizational priority.

PI_NAMEs: SOX-HARRIS, ALEX  (contact)

PROJECT_TERMS: Accountability;addiction;Address;alcohol abuse therapy;alcohol use disorder;Applications Grants;Area;Automobile Driving;Award;Awareness;bone;care outcomes;career;Caring;Carpal Tunnel Syndrome;Chronic low back pain;Clinical;clinical practice;common treatment;cost;Data Aggregation;Degenerative polyarthritis;Deimplementation;design;Ecological Bias;experience;falls;Funding;General Anesthesia;Grant;Hand;Health;health care delivery;health care quality;Health Services;Health Services Research;Healthcare;Healthcare Systems;hip replacement arthroplasty;Homogeneously Staining Region;implementation research;implementation science;improved;improved outcome;indexing;Individual;Informed Consent;innovation;insight;interest;Internal Medicine;Joints;Journals;knee replacement arthroplasty;Literature;Low Back Pain;mange;Manuscripts;Measurement;Measures;Medical;Mentors;Methodology;Methods;Modeling;modifiable risk;Motivation;next generation;Operative Surgical Procedures;Orthopedics;Paper;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Policies;Postoperative Pain;Postoperative Period;precision medicine;predictive modeling;Procedures;Process;programs;Publishing;Quality of Care;Replacement Arthroplasty;Research;Research Personnel;Risk;Risk Factors;risk stratification;Role;Scientist;shared decision making;substance abuse treatment;surgery outcome;Surgical complication;Surgical Models;System;Testing;Time;United States Agency for Healthcare Research and Quality;Validation;Work

PROJECT_TITLE: HSR&D Senior Research Career Scientist Award

STUDY_SECTION_NAME: HSR-7 Capacity Building[HSR7]


ORG_CITY: ANN ARBOR

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: MI

PHR: Clinical provider burnout is a key indicator of how well a health care system is functioning. Reducing mental health provider (MHP) burnout could improve patient access to care, quality of care, and improve employee engagement, which are core components of VHA's priorities and strategic plan. We propose to conduct the largest and most comprehensive study to date on the systematic, facility-level predictors and consequences of MHP burnout. VHA can use the findings from this longitudinal, mixed methods study to facilitative future planning and interventions to improve MHP burnout, employee engagement, and patient outcomes. Supported by a wide range of VHA and community partners and stakeholders, our findings could be of clinical and financial value to VHA, its providers, and patients. Our work will contribute to broad healthcare improvements within VHA, and will generate new insights for healthcare delivery, informing efforts to address burnout in MHPs and other clinical providers.

PI_NAMEs: ZIVIN, KARA  (contact)

PROJECT_TERMS: Address;Administrator;Area;Behavior;burnout;care delivery;Caregivers;Caring;Censuses;Characteristics;Clinical;community partners;contextual factors;Cross-Sectional Studies;Data;Data Analyses;Data Collection;Data Sources;Depersonalization;design;Development;direct patient care;Educational process of instructing;Emotional;Employee;Employee Engagement;Epidemic;Equipment and supply inventories;exhaustion;experience;Feedback;Feeling;Focus Groups;follow-up;Future;Health;health care delivery;Health Personnel;Health Services Accessibility;Health system;Healthcare;Healthcare Systems;Hour;implementation study;improved;Individual;innovation;Inpatients;insight;Intervention;Interview;Job Satisfaction;Joints;Leadership;Learning;Light;Link;longitudinal analysis;Measures;Mediating;Mental Health;Mental Health Services;Methods;Mission;Monitor;Occupations;organizational climate;Outpatients;Patient risk;Patient-Focused Outcomes;Patients;Perception;Performance;Phase;Physicians;Policies;Prevalence;Primary Care Physician;Productivity;programs;Provider;provider factors;Psychiatric Hospitals;Psychiatrist;Psychologist;Qualifying;Quality of Care;Reaction;Recommendation;Reporting;Research;Research Personnel;research study;Resources;Risk Management;Sampling;satisfaction;Site;Social Workers;Specialist;Strategic Planning;stressor;Structure;Suicide prevention;Surveys;System;Testing;Time;Translating;Variant;Veterans;Wait Time;Work;Workplace

PROJECT_TITLE: Caring for the caregiver: predictors and consequences of VA mental health provider burnout

STUDY_SECTION_NAME: HSR-5 Health Care System Organization and Delivery and Women's Health[HSR5]


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Epilepsy;Neurodegenerative;Neurosciences

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE We will target a group of patients with a particularly challenging epilepsy – mesial temporal lobe epilepsy with preserved memory – in a trial of network-based recording and neuromodulation using a new device. In a small cohort, brain modulation by low frequency stimulation at multiple regions to control seizures will be performed to establish proof of concept for a larger multi-center trial.

PI_NAMEs: AAZHANG, BEHNAAM ;BANKIM BEHARI PATI, SANDIPAN PATI ;TANDON, NITIN  (contact);WORRELL, GREGORY A

PROGRAM_OFFICER_NAME: GROSS, BROOKS ANDREW

PROJECT_TERMS: American;Amygdaloid structure;Animal Model;Anterior;Area;Brain;Cell Nucleus;Charge;Chronic;Clinic;cohort;Data;density;Detection;Devices;diaries;Disabling;Drug resistance;Electrodes;Electroencephalography;Electronics;Elements;entorhinal cortex;Epilepsy;Episodic memory;Excision;first-in-human;Freedom;Frequencies;Graph;Hippocampus;Human;Implant;implantation;Implanted Electrodes;improved;Individual;innovation;Institution;Insula of Reil;Intervention;Intractable Epilepsy;Location;Maps;Measures;medial temporal lobe;Memory;Memory Loss;Monitor;Morbidity - disease rate;mortality;Movement Disorders;Multicenter Trials;Neocortex;network models;Network-based;neural;neuromechanism;neuroregulation;novel;novel strategies;Operative Surgical Procedures;palliative;Parahippocampal Gyrus;Partial Epilepsies;Patient Selection;Patients;Pattern;Performance;pharmacologic;Physiologic pulse;piriform cortex;preservation;Process;programs;recruit;Refractory;Research;response;Rest;Rice;Risk;Safety;safety and feasibility;Schedule;Seizures;Severities;Site;standard of care;Structure;System;Techniques;Technology;Temporal Lobe Epilepsy;Thalamic structure;Therapeutic;therapeutically effective;Universities;Width;Work

PROJECT_TITLE: Network based neuro-modulation for mesial temporal lobe epilepsy


NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: The efficiency of synaptic transmission relies on the maintenance of a high number of receptors at the postsynaptic membrane. This proposal will explore the role of muscle calmodulin kinase II-related anchoring protein (αkap) on synaptic development and AChR stability of healthy and compromised neuromuscular synapses. These studies will have a significant impact in understanding the basic mechanisms that underlie the stability of receptors and will be relevant to developing new approaches for treating neurological diseases where the number/density of receptors is compromised.

PI_NAMEs: AKAABOUNE, MOHAMMED  (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Adult;Affect;alpha synuclein;alpha-dystrobrevin;Animals;Biological Models;Biology;Ca(2+)-Calmodulin Dependent Protein Kinase;Calcium;Cell surface;Cells;Cholinergic Receptors;Complex;Data;density;Development;Dose;Dystrophin;Endocytosis;Excision;Exocytosis;gain of function;Genes;Glycoproteins;Goals;Impairment;In Vitro;in vivo Model;knock-down;Knock-out;Life;Link;loss of function;Maintenance;Metabolic;Modeling;Molecular;Motor Neurons;multicatalytic endopeptidase complex;Mus;Muscle;Muscle Cells;Muscle Fibers;Mutant Strains Mice;Nervous System Disorder;neuromuscular;Neuromuscular Diseases;Neuromuscular Junction;neuromuscular system;Nicotinic Receptors;novel strategies;Outcome Study;overexpression;Pathway interactions;Peptide Hydrolases;Phenotype;Play;postnatal;postnatal period;postsynaptic;Postsynaptic Membrane;Process;protein complex;Proteins;receptor;receptor density;receptor recycling;Role;Scaffolding Protein;Shapes;Site;Skeletal Muscle;small hairpin RNA;Spinal;Synapses;synaptic pruning;Synaptic Receptors;Synaptic Transmission;synaptogenesis;syntrophin;syntrophin alpha1;System;Testing;Time;trafficking;Transcript;Transfection;Ubiquitin;ubiquitin isopeptidase;Work;young adult

PROJECT_TITLE: The effect of muscle-specific anchoring protein on the biology of the Neuromuscular system


PHR: Project Narrative In this proposal, we investigate the neuronal underpinnings of transcranial magnetic stimulation (TMS) in the cerebellum using a combination of electrophysiological experiments and computational modeling. We will first use boundary element models of the in vitro setup to study how the conductivity boundaries in in vitro studies can distort and sometimes weaken or even reverse the induced E-field and design a solution to facilitate reliable TMS stimulation in vitro. We will then systematically characterize the cellular responses to TMS in an in vitro turtle cerebellum and then use those insights to understand the TMS responses in the human cerebellum in vivo in a saccade study.

PI_NAMEs: PATEL, PADMAVATHI SUNDARAM (contact)

PROGRAM_OFFICER_NAME: HWANG, GRACE MEI-HUA

PROJECT_TERMS: 3-Dimensional;Area;Axon;Bathing;Boundary Elements;Brain;BRAIN initiative;Brain Stem;Cell Nucleus;Cells;Cerebellar Cortex;Cerebellar vermis structure;Cerebellum;Computer Models;Computing Methodologies;cranium;Data;data archive;design;Devices;Early identification;Electric Stimulation;Electrodes;Electroencephalography;Electrooculogram;Electrophysiology (science);Elements;experimental analysis;Experimental Models;extracellular;Eye;Fiber;Geometry;Goals;granule cell;Head;Human;improved;In Vitro;in vitro Model;in vivo;Inferior;insight;Lateral;Link;man;Measurement;Measures;Methods;Microanatomy;Modeling;Monitor;mossy fiber;neural;Neurons;novel;Olives - dietary;Pontine structure;Population;Preparation;Procedures;Process;Purkinje Cells;Reptiles;Resolution;response;Role;Saccades;Saline;simulation;Slice;Source;source localization;Specific qualifier value;Tissues;Transcranial magnetic stimulation;Turtles

PROJECT_TITLE: Cellular Mechanisms of Transcranial Magnetic Stimulation in Cerebellar Cortex


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);Biodefense and Related Countermeasures;Brain Disorders;Dementia;Emerging Infectious Diseases;Infectious Diseases;Neurodegenerative;Neurosciences;Rare Diseases;Transmissible Spongiform Encephalopathy (TSE)

ORG_CITY: LA JOLLA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Prion diseases are fatal neurodegenerative disorders with no curative treatment available. We have engineered a new mouse model expressing a modified prion protein that develops severe neuronal pathology similar to humans and animals with prion disease. We expect that the proposed studies will reveal protein interactions and pathways that incite neuronal death in prion disease, and will uncover new targets for therapeutic development.

PI_NAMEs: SIGURDSON, CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Affect;Age;alpha synuclein;Alzheimer's Disease;Alzheimer's disease model;Amino Acid Substitution;Amyloid beta-Protein;Animals;Automobile Driving;Autophagosome;Binding;Biochemical;bone;Brain;Brain Diseases;Calcium Signaling;Chronic;Clinical;Creutzfeldt-Jakob Syndrome;curative treatments;Data;Deposition;Disease;Dissection;Engineering;excitotoxicity;Extracellular Protein;Functional disorder;Gliosis;Glutamate Receptor;Glutamates;Glycoproteins;Goals;Health;Histologic;Human;Impairment;In Vitro;in vivo;Infection;insight;Knock-in;Knock-in Mouse;Link;Location;Maintenance;Mass Spectrum Analysis;Mediating;Modeling;Molecular;Molecular Conformation;Morphology;mouse model;Mus;mutant;N-terminal;Nerve Degeneration;Neurites;Neurodegenerative Disorders;Neurologic Signs;neuron loss;Neurons;neurotoxic;neurotoxicity;neurotransmission;new therapeutic target;Outcome;Pathologic;Pathology;Pathway interactions;Patients;Phosphorylation;Point Mutation;Polysaccharides;Post-Translational Protein Processing;postsynaptic;postsynaptic neurons;presynaptic;presynaptic neurons;Prion Diseases;Prions;protein aggregation;protein expression;protein function;protein structure;Proteins;Proteomics;proteostasis;proteostasis loss;PrP;PrPSc Proteins;Rare Diseases;Reactive Oxygen Species;receptor function;receptor sensitivity;response;Role;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Signaling Protein;Structure;Synapses;synaptic function;Synaptic Membranes;Synaptic Receptors;Synaptosomes;tau aggregation;Testing;therapeutic development;Toxic effect;trafficking;Transgenic Mice;Vacuole;Variant;Varicosity;vesicle transport

PROJECT_TITLE: Molecular basis of prion protein-induced neurodegeneration

STUDY_SECTION: CMND

STUDY_SECTION_NAME: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]


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;Dementia;Hypertension;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: SAN DIEGO

ORG_NAME: SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE Vascular contributions to cognitive impairment and dementia (VCID) is the second leading cause of dementia behind Alzheimer’s disease (AD) but despite the massive impact of VCID in the expanding elderly population, its pathogenesis is still only poorly understood and effective treatments are lacking. We have found that mild hypoxia triggers blood-brain barrier (BBB) disruption in young mice that is exacerbated by microglial depletion, and that hypoxia-induced BBB disruption is far greater in aged mice, suggesting that microglia play an important vasculoprotective role in young mice, but this mechanism may be less effective in the aged brain. As aging induces the appearance of a “primed”, pro-inflammatory microglial phenotype, here we will test the hypothesis that : (1) mild hypoxia triggers vascular leak and microhemorrhage in the brain, resulting in neuronal damage and cognitive decline, (2) vascular disruption is worse in the aged and the hypertensive, (3) microglia play an important vasculoprotective role in stabilizing the BBB, but this declines with age, and (4) repopulating the aged brain with young microglia or attenuation of microglial activation state, could stabilize the BBB and reduce cognitive impairment.

PI_NAMEs: MILNER, D. RICHARD (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Address;Age;age effect;age related;age related decline;aged;Aging;aging brain;Alzheimer's Disease;antagonist;Appearance;Astrocytes;Attenuated;attenuation;Behavior;Blood - brain barrier anatomy;Blood Vessels;blood-brain barrier disruption;Brain;Brain region;cerebral hypoperfusion;cerebrovascular;Chronic;Cognition;Cognitive;comorbidity;Consensus;Coupling;Data;defined contribution;Dementia;Dose;effective therapy;Elderly;Fibrinogen;Flow Cytometry;Gel;Gelatinase B;Gender;glial activation;Health;Hemorrhage;Hypertension;hypertensive;Hypoxia;Impaired cognition;Inflammatory;insight;Intervention;Knockout Mice;Lead;Link;long term memory;Macrophage Colony-Stimulating Factor Receptor;Maintenance;Methods;Microglia;Minocycline;Modeling;Mouse Strains;Mus;Neurons;normotensive;novel;old mice;Pathogenesis;Peptides;Phenotype;Play;Population;prevent;protein expression;Proteins;response;Role;Severities;Spinal Cord;Testing;Therapeutic;Tight Junctions;United States;vascular cognitive impairment and dementia;Vascular resistance

PROJECT_TITLE: The protective role of microglia in preventing hypoxic disruption of blood-brain barrier integrity and VCID

STUDY_SECTION: BINP

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


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;Cardiovascular;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: PITTSBURGH

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative In many neurodegenerative diseases, including Alzheimer's disease (AD) and AD-related dementias (ADRD), proteins accumulate outside blood vessels, causing progressive damage to the blood-brain barrier (BBB). Investigating the mechanisms of interaction between the proteins aggregates and the BBB is crucial to identify therapeutic opportunities to preserve cerebrovascular health and BBB function. This project's goals are to investigate the effects of aberrant protein aggregation on the structural and functional properties of the BBB and, conversely, to evaluate the impact of physical disruption of the BBB on aberrant protein aggregation.

PI_NAMEs: SILVA, AFONSO C (contact)

PROJECT_TERMS: Affect;Age;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Amyloid beta-Protein;Arterial Disorder;autosome;Basement membrane;Behavioral;Behavioral Assay;Biochemical;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Preservation;Blood Vessels;blood-brain barrier disruption;blood-brain barrier function;blood-brain barrier permeabilization;Brain;brain tissue;Carrier Proteins;Cerebral Amyloid Angiopathy;Cerebrovascular Circulation;cerebrovascular health;cerebrovascular reactivity;Cerebrovascular system;Cerebrum;Cessation of life;Chronic;Data;Dementia;Deposition;Endothelial Cells;experimental study;Extracellular Matrix;Functional impairment;functional status;Goals;Histologic;Homeostasis;Image;Impaired cognition;Investigation;Knowledge;Link;Lymphatic System;Measures;Mechanics;Microbubbles;Microvascular Dysfunction;Molecular;mouse model;Nervous System Disorder;Neurodegenerative Disorders;neurovascular unit;new therapeutic target;NOTCH3 gene;Pathologic;Pathology;Peptide Hydrolases;Pericytes;Plasma;pre-clinical;preservation;Property;protein aggregation;protein transport;Proteins;receptor;Role;Smooth Muscle Myocytes;Subcortical Infarctions;Subcortical Leukoencephalopathy;tau Proteins;Techniques;Testing;Therapeutic;ultrasound;Vascular Smooth Muscle;Vascular System

PROJECT_TITLE: Preclinical investigation of common mechanistic links between aberrant protein aggregation and blood-brain barrier dysfunction in Alzheimer's disease and Alzheimer's related dementias (AD/ADRD)


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;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Growing evidence suggests that pure Alzheimer’s disease is rare among the human population, but strikingly a significant proportion of individuals with Alzheimer’s present with vascular comorbidities in tandem with plaque deposition. Both Alzheimer’s and VCID are a major unment medical need, with no FDA approved therapy. Defining the role of abberant astrocyte inflammatory response in these conditions and whether RelA is a factor in these responses will enable new lines of development for future therapeutic targeting of these pathways to either restrain or enhance critical facets of astrocyte response to the comorbid disease milieu.

PI_NAMEs: MORGANTI, JOSH  (contact)

PROJECT_TERMS: abeta deposition;aging population;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;Animal Disease Models;Animal Model;Astrocytes;astrogliosis;Automobile Driving;Blood Vessels;blood-brain barrier permeabilization;Brain;Cells;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;comorbidity;conditional knockout;Coupling;Data;Degenerative Disorder;Dementia;Deposition;Development;Disease;disease model;Environment;Excision;Exposure to;FDA approved;Functional disorder;Future;Gliosis;Healthcare;Human;human model;Impaired cognition;Individual;Inflammatory;Inflammatory Response;innovation;Ischemia;Knowledge;Label;Lead;Link;Mediating;Medical;Microglia;Modality;Modeling;Multiple Sclerosis;Neuroglia;neuroinflammation;Neurological outcome;Neuronal Dysfunction;Neurons;new therapeutic target;NF-kappa B;novel;Pathologic;Pathology;Pathway interactions;Phenotype;Play;Population;Publishing;Recording of previous events;Recovery of Function;Research;response;response to injury;restraint;Risk;Role;Senile Plaques;Shapes;Signal Pathway;Signal Transduction;Spinal cord injury;Synapses;Testing;therapeutic target;Tissues;vascular cognitive impairment and dementia;vascular contributions;vascular injury;vascular risk factor;Work

PROJECT_TITLE: Inflammatory contributions of astrocytic RelA in comorbid VCID/AD


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_DEPT: NEUROLOGY

PHR: Project Narrative Arteriosclerotic common carotid artery (CCA) stenosis causes chronic CCA hypoperfusion and white matter injury (WMI), which is closely related to memory loss, cognitive dysfunction and dementia. A key feature of CCA hypoperfusion is massive loss of oligodendrocytes which is the only cells for producing myelin, the major component of white matter fiber, leading to WMI. Thus, oligodendrocyte replacement therapy is a critical prerequisite for white matter restoration and cognitive dysfunction and dementia. CCA hypoperfusion activate astrocytes, which will eventually form glial scar that impedes the regeneration and reestablishment of fiber networks. The proposed experiment will use a novel strategy to convert activated astrocytes into oligodendrocytes in situ in a novel model CCA hypoperfusion models that mimic arteriosclerotic CCA stenosis. Thus, we will convert the detrimental glial scar into beneficial myelin-producing cells, restore white matter structure and function and enhance cognitive function. We expect to develop new therapeutic interventions that can repair WMI as well as cognitive dysfunction and dementia.

PI_NAMEs: CAO, GUODONG  (contact)

PROJECT_TERMS: Action Potentials;Aging;Alzheimer's Disease;Area;Astrocytes;Axon;axon injury;axonal sprouting;Axonal Transport;behavior test;Behavioral;Brain;Brain Ischemia;brain tissue;Carotid Stenosis;Cause of Death;Cell Reprogramming;Cell Survival;Cells;Central Nervous System Diseases;central nervous system injury;cerebral hypoperfusion;Cessation of life;Chronic;Cicatrix;Cognitive;cognitive enhancement;cognitive function;cognitive recovery;Collaborations;Common carotid artery;Dementia;Demyelinations;Diffusion Magnetic Resonance Imaging;Electron Microscopy;Electrophysiology (science);Ensure;Environment;experimental study;Female;Fiber;Functional disorder;Gender;Gliosis;Goals;Guidelines;hypoperfusion;Image;immunogenicity;Impaired cognition;improved;In Situ;In Vitro;in vivo;Infarction;Infusion procedures;Injury;injury and repair;innovation;insight;Intervention;Ischemia;Lentivirus Vector;Link;Long-Term Potentiation;Magnetic Resonance Imaging;male;Measurement;Memory Loss;Methods;Modeling;mouse model;Mus;Myelin;myelination;Names;Natural regeneration;Needles;Nerve Fibers;novel;novel strategies;novel therapeutic intervention;novel therapeutics;old mice;oligodendrocyte progenitor;Oligodendroglia;Outcome Assessment;overexpression;Pathogenicity;Process;programs;Proliferating;Proteins;Recombinants;Recovery;Recovery of Function;remyelination;repaired;Replacement Therapy;restoration;Role;Sensorimotor functions;stem cell differentiation;stem cells;Structure;Techniques;Testing;therapeutic evaluation;transcription factor;translational potential;vascular cognitive impairment and dementia;white matter;white matter injury

PROJECT_TITLE: White Matter Restoration in Vascular Cognitive Impairment and dementia

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Neurodegenerative;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: Project Narrative Abnormal neuronal activity and protein-based cellular toxicity have been a hallmark of many neurodegenerative diseases. We propose to reconcile and link these two distinct disease models by identifying how increased neuronal activity drives production of toxic proteins and possibly toxic RNA species due to a genetic mutation associated with FTD/ALS. Upon completion of this proposed work, we will establish the foundation for the cause and effect relationship between abnormal neuronal activity and toxic mechanisms that contribute to the FTD/ALS neurodegenerative disease spectrum, while revealing new therapeutic opportunities for disease intervention.

PI_NAMEs: HAEUSLER, AARON RAYMOND (contact)

PROJECT_TERMS: Acute;Age;age acceleration;age related;Aging;ALS patients;Amyotrophic Lateral Sclerosis;Animal Model;Appearance;Autopsy;Bacterial Artificial Chromosomes;Behavioral;Biochemical;biological adaptation to stress;Biological Assay;C9ORF72;Cell Nucleus;Cells;Cellular Stress;Chronic;Cytoplasm;Defect;Dipeptides;Disease;disease model;DNA Sequence Alteration;Electroencephalography;Epilepsy;epileptiform;Etiology;excitotoxicity;Foundations;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;gain of function;genetic approach;Genetic Transcription;Half-Life;human induced pluripotent stem cells;Imaging Techniques;In Vitro;in vivo;in vivo Model;Induced pluripotent stem cell derived neurons;Intervention;Investigation;Link;loss of function;Measures;Modeling;Motor;mouse model;multi-electrode arrays;Mus;Mutation;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;Neuromuscular Diseases;Neurons;Neuropathogenesis;neurophysiology;neuroprotection;neurotoxic;novel;novel therapeutic intervention;novel therapeutics;Nucleoproteins;Nucleotides;Pathogenesis;Pathogenicity;Pathologic;Pathology;patient derived induced pluripotent stem cells;Patients;pharmacologic;Phenotype;Physiological;prevent;Production;Proteins;Reporting;Research Proposals;response;RNA;Role;serial imaging;spatiotemporal;Stress;stressor;Techniques;Testing;Tissues;Toxic effect;Transcript;transcriptome;Translations;Variant;Work

PROJECT_TITLE: The pathogenic relationship between neuronal activity and C9orf72-linked neurodegeneration


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);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences

ORG_CITY: NEW YORK

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

ORG_STATE: NY

PHR: Transactive response DNA-binding protein 43 kDa (TDP-43) is linked to memory loss and abnormal behaviors in aging-related neurological disorders. The effects of neuronal TDP-43 dysregulation on brain function have been studied intensely, but its roles in non-neuronal cells like astrocytes are poorly understood. The proposed research will examine how astrocytic TDP-43 dysfunction affects astrocytic-neuronal interactions, neuronal activities, and cognitive functions, and investigate novel intercellular mechanisms underlying memory loss in neurodegenerative disease.

PI_NAMEs: ORR, ANNA GOLDSHMIDT (contact)

PROJECT_TERMS: Ablation;Affect;age related neurodegeneration;aging related;Alzheimer's Disease;Alzheimer's disease patient;Amyotrophic Lateral Sclerosis;Animal Model;Astrocytes;Behavior;behavior measurement;Behavioral;Brain;Brain region;brain tissue;Cell Culture Techniques;cell type;Cells;chemokine;chemokine receptor;Coculture Techniques;cognitive function;Complex;CXC chemokine receptor 3;CXCL10 gene;CXCL9 gene;CXCR3 gene;Cytoplasm;Data;Dementia;Disease;DNA-Binding Proteins;Elderly;Electrophysiology (science);Experimental Models;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;Gene Expression;Gene Expression Profile;Genetic;Genetic Transcription;Glutamates;hippocampal sclerosis;Hippocampus;Human;Impaired cognition;Impairment;In Vitro;inducible gene expression;Interferons;Investigation;knock-down;Knock-out;Link;Mediating;Memory;Memory impairment;Memory Loss;Modeling;Molecular;mortality;motor deficit;mouse model;Mus;mutant;N-Methyl-D-Aspartate Receptors;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;Neuroglia;Neuronal Plasticity;Neurons;Neurophysiology - biologic function;neurotransmission;Normal Range;novel;novel therapeutic intervention;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;pharmacologic;Play;Population;Premature Mortality;prevent;Prevention;Process;protein TDP-43;Research;response;Role;selective expression;Signal Transduction;Testing;transcriptome sequencing;transgene expression;Transgenic Mice;transmission process;Work

PROJECT_TITLE: Defining the Effects of Astrocytic TDP-43 Dysregulation on Hippocampal Function


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Clinical Research;Clinical Trials and Supportive Activities;Conditions Affecting the Embryonic and Fetal Periods;Drug Abuse (NIDA only);Health Services;Maternal Health;Mental Health;Mental Illness;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Substance Misuse;Women's Health Research

ORG_CITY: Oakland

ORG_NAME: KAISER FOUNDATION RESEARCH INSTITUTE

PHR: PUBLIC HEALTH RELEVANCE STATEMENT Over the past decade, marijuana use during pregnancy has dramatically increased in conjunction with growing legalization and accessibility; yet our understanding of how the development of the child exposed to marijuana in utero may be impacted is poor. This longitudinal birth cohort study will evaluate the effects of prenatal marijuana exposure on neurodevelopmental impairments, behavioral disorders and mental health outcomes in over 420,000 children, up to 13 years of age, who were born between 2010-2021 at Kaiser Permanente Northern California hospitals to women universally screened for prenatal use of marijuana and other substances via self-report and urine toxicology tests. Findings from this study will provide pregnant women and clinicians with much needed data about the longer-term impacts of in utero marijuana exposure on the health of the child.

PI_NAMEs: AVALOS, LYNDSAY AMMON (contact);YOUNG-WOLFF, KELLY CORINNE

PROGRAM_OFFICER_NAME: VIDAL, SARAH

PROJECT_TERMS: 13 year old;Accounting;Address;Adolescent;Adverse effects;Affect;Anti-emetics;Anxiety;Attention deficit hyperactivity disorder;autism spectrum disorder;Behavior;Behavior Disorders;Biological;Birth;boys;California;Child;Child Development;Child Health;Clinical;Clinical Data;Code;Cognition Disorders;Cohort Studies;Data;design;Development;Developmental Delay Disorders;Diagnosis;Disease;Drug usage;drug use in pregnancy;drug use screening;Electronic Health Record;endogenous cannabinoid system;epidemiology study;experience;Exposure to;externalizing behavior;fetal;Fetal Development;fetal marijuana exposure;First Pregnancy Trimester;girls;Hospitals;ICD-9;in utero;Information Systems;innovation;Integrated Health Care Systems;International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10);Legal;Marijuana;Marijuana Smoking;marijuana use;marijuana use in pregnancy;marijuana user;Maternal Age;Measures;Mental Depression;Mental Health;Methodology;Mothers;motor disorder;multidisciplinary;Nervous System Physiology;neurodevelopment;Neurodevelopmental Impairment;offspring;Outcome;Patient Self-Report;Personal Satisfaction;Policies;Population Heterogeneity;Pregnancy;pregnant;Pregnant Women;Premature Birth;prenatal;prenatal exposure;prenatal testing;Prevalence;Prevention program;Public Health;public health relevance;Recommendation;Reporting;Research;Resources;Risk;Sampling;screening;screening program;Services;sex;Sex Differences;standard care;substance use;Substance Use Disorder;Testing;Tetrahydrocannabinol;Tobacco;Toxicology;treatment program;United States National Academy of Sciences;Urine;Well Child Visits;Woman;Women's cohort;young adult

PROJECT_TITLE: Impact of in utero Marijuana Exposure on Neurodevelopment, Behavior and Mental Health: A Longitudinal Birth Cohort Study

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


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Social Determinants of Health

ORG_DEPT: MISCELLANEOUS

ORG_NAME: DUKE UNIVERSITY

PHR: Project Narrative – Sexual and Gender Minority (SGM) Mental Health In Low and Middle Income Countries (SMILE) SMILE will characterize the mental health symptomatology and needs of seven different SGM groups in three culturally and contextually distinct LMICs. Respondent Driven Sampling (RDS) as well as mass media recruitment will be used to enroll a longitudinal cohort; the cultural, contextual, interpersonal, and individual determinants of mental health outcomes over 24 months will be identified. Discrete Choice Experiments (DCEs) will be used to elicit SGM preferences for different characteristics of evidence-based mental health treatments (EBTs) that can be feasibly provided and sustained for this very vulnerable population.

PI_NAMEs: WHETTEN, KATHRYN  (contact)

PROGRAM_OFFICER_NAME: VEDHAM, VIDYA

PROJECT_TERMS: Abuse Reporting;Acceleration;Address;alcohol and other drug;Alcohol dependence;Anxiety;Attention;Biologic Characteristic;Brazil;Caring;Characteristics;cohort;Cohort Studies;combat veteran;Country;Cross-Sectional Studies;Data;Development;Discrimination;Drug Addiction;Enrollment;evidence base;Evidence based treatment;Exclusion;experimental study;Family;family support;Feeling suicidal;Gender;Gender Identity;gender minority group;gender minority health research;gender nonconforming;Goals;Government;Grief reaction;Healthcare Systems;Heterosexuals;HIV;HIV/STD;Income;Individual;interest;Intervention;Kenya;Learning;longitudinal analysis;Longitudinal cohort;Longitudinal cohort study;low and middle-income countries;Mass Media;Media Campaign;men;men who have sex with men;Mental Depression;Mental disorders;Mental Health;Mental Health Services;Methods;mHealth;Modality;Modeling;Morbidity - disease rate;National Institute of Mental Health;NIH Program Announcements;Observational Study;Online Systems;Outcome;Participant;Persons;Police;Policies;Politics;Population;Post-Traumatic Stress Disorders;preference;Prevalence;programs;protective factors;Provider;Public Policy;recruit;Religion;Research;Resource-limited setting;Resources;Respondent;Risk Factors;risk prediction;Rural;Sampling;scale up;Sex Behavior;Sexual and Gender Minorities;sexual minority group;sexual minority health;Social Network;social stigma;Speed;STI prevention;stressor;Substance abuse problem;Support System;Surveys;symptomatology;System;Time;transgender men;transgender women;Translations;United States National Institutes of Health;Variant;Vietnam;Vulnerable Populations;Woman

PROJECT_TITLE: SMILE

STUDY_SECTION: HDEP

STUDY_SECTION_NAME: Health Disparities and Equity Promotion Study Section[HDEP]


ORG_CITY: SALT LAKE CITY

ORG_NAME: VA SALT LAKE CITY HEALTHCARE SYSTEM

ORG_STATE: UT

PHR: The Veterans Health Administration (VHA) faces new and significant challenges with long COVID, with 10-50% of Veterans who tested positive for COVID experiencing this condition. Long COVID can involve multiple symptoms and biologic systems, ranging in severity and regularity that can last weeks to months after initial COVID infection. One of the major challenges with long COVID is that it is difficult to diagnose since a consensus has not been reached on the criteria for defining long COVID. Lack of a universal definition of long COVID hinders needed research to identify effective treatments and management strategies. Increasingly, evidence suggests that historically underserved populations may have a higher risk of long COVID and its adverse outcomes. VHA has a unique opportunity to play a critical role in defining long COVID by leveraging its multiple high-quality data sources and to advance research on Veteran’s experiences with long COVID, including possible health inequities.

PI_NAMEs: KNIGHT, SARA J;MOHANTY, APRIL F (contact)

PROJECT_TERMS: acute COVID-19;acute infection;Address;adverse outcome;biological systems;care delivery;Caring;Chronic;Clinical;Clinical Management;clinical phenotype;Code;Consensus;COVID-19;crosslink;Data;data sharing networks;Data Sources;design;Diagnosis;disease diagnosis;effective therapy;Electronic Health Record;Epidemiology;Evaluation;Evidence based practice;experience;Face;Goals;Health;health assessment;health inequalities;health service use;Health Services Accessibility;Health Surveys;high risk;improved;Incidence;Inequity;informant;innovation;International Classification of Diseases;Interview;Knowledge;Long COVID;Medical Care Team;Methodology;Methods;military veteran;Mission;Modeling;Morbidity - disease rate;Nonpharmacologic Therapy;novel;Outcome;Pain;Patients;Pattern;Pharmacological Treatment;Phenotype;Play;Population;Post-Acute Sequelae of SARS-CoV-2 Infection;post-COVID-19;Practice Management;Prevalence;Provider;Public Health;Quality of life;Rehabilitation therapy;Reporting;Research;Risk;Role;SARS-CoV-2 infection;SARS-CoV-2 infection history;SARS-CoV-2 positive;Self Care;Service delivery model;Severities;social health determinants;Standardization;Surveys;symptom cluster;symptomatology;Symptoms;Syndrome;System;Testing;Underserved Population;unsupervised clustering;Veterans;Veterans Health Administration;whole health

PROJECT_TITLE: COvid Post-Exposure Evaluation and Symptomatology (COPES) Center: Identifying Post-COVID Phenotypes and Related Health Inequities


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Infectious Diseases;Infertility;Prevention;Vector-Borne Diseases;Women's Health Research

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

ORG_STATE: CT

PHR: Project Narrative Secretory cells in oviducts are essential for gamete survival and fertilization. This project utilizes a novel Drosophila model to genetically interrogate the role of conserved transcription factors in oviduct secretory cells and identify novel factors for sperm attraction and ovulation. Through this work, we will gain mechanistic insights into the precise regulation of oviduct secretions, which will aid the development of new approaches for contraception, treating infertility, and controlling malaria-bearing mosquito population.

PI_NAMEs: SUN, JIANJUN  (contact)

PROGRAM_OFFICER_NAME: JOHNSTON, DANIEL STEPHEN

PROJECT_TERMS: Ablation;Animals;Arrestins;Attention;Cell Physiology;Cells;Collection;Contraceptive Agents;Contraceptive methods;Culicidae;Data;Development;Drosophila genus;Ecdysone;Embryonic Development;extracellular vesicles;falls;Family;Female;female reproductive tract;Fertilization;Future;Genetic;genetic manipulation;Genetic Models;Genetic Screening;Germ Cells;Gland;Graafian Follicles;Health;Human;improved;in vivo;Infertility;Insecta;insight;Investigation;Knowledge;Malaria;Malignant neoplasm of ovary;Malignant Neoplasms;Mammalian Oviducts;Mediating;Medicine;Methods;Modeling;Molecular;Morphology;mosquito reproduction;Nature;new therapeutic target;novel;novel strategies;Nuclear Family;Nuclear Receptors;Orthologous Gene;Ovary;Ovulation;Ovum;Pathway interactions;Physiological;Physiology;Play;Population;Process;Proteins;Regulation;Reporting;Reproductive Physiology;Research;Resolution;Role;Rupture;Scientific Inquiry;Secretory Cell;Serous;Signal Pathway;Signal Transduction;sperm cell;Steroids;System;Testing;Therapeutic;tool;transcription factor;Tube;Uterus;vector;vesicular release;Work

PROJECT_TITLE: Physiological Functions of Female Reproductive Tract Secretions

STUDY_SECTION: CMIR

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


ORG_CITY: MADISON

ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

ORG_STATE: WI

PHR: Post-Acute Sequelae of SARSCoV-2 (PASC), a chronic multisymptom illness, is affecting an alarming number of Veterans infected by the COVID-19 virus. PASC symptoms are often debilitating and can include various combinations of fatigue, pain, irritable bowel, and brain fog, severely impacting health quality. Importantly, exercise is reported to worsen the symptoms of PASC, a condition of post-exertional malaise (PEM), which interferes with recovery. The causes of PASC symptoms and their exacerbation with exercise are unknown, limiting treatment options. Two candidate mechanisms are disturbed gut microbiome and neuroinflammation. The proposed research will test whether Veterans with PASC exhibit PEM and whether exercise disrupts the gut microbiome and augments neuroinflammation. This research will improve our understanding of the causes of PASC-related symptoms and begin a path towards individualized treatment. These goals are directly in line with the mission of the Department of Veterans Affairs to care for those who have served this country.

PI_NAMEs: COOK, DANE B. (contact)

PROJECT_TERMS: 2019-nCoV;Acute;Address;Adverse effects;Affect;American;Area;Back;Biological Markers;Boston;Brain;brain fog;Caring;Characteristics;Chicago;Chronic;Chronic Fatigue Syndrome;Clinical;Cognition;cognitive performance;combat;comparison control;Country;COVID-19;COVID-19 pandemic;COVID-19 survivors;Data;data management;Data Set;data warehouse;Databases;Development;Disease;effective intervention;empowerment;Equilibrium;Event;Exercise;Exertion;Exhibits;experience;Fatigue;Foundations;Frequencies;Functional disorder;Functional impairment;functional independence;Gait;Genetic;genetic predictors;Goals;gut microbiome;Health;Impaired cognition;Impairment;improved;Incidence;Individual;individualized medicine;Inflammation;Inflammatory;insight;Interleukin-6;Intervention;Intestines;Investigation;Life;Long COVID;Malaise;Medical center;Metagenomics;microbiome alteration;microbiome composition;military veteran;Mission;Modeling;neuroinflammation;Neurologic;Outcome;Pain;pain symptom;Participant;patient population;Patient-Focused Outcomes;Patients;Peripheral;Persian Gulf Syndrome;persistent symptom;personalized medicine;Phenotype;Physical activity;Physical Efforts;Physiological;Population;Positioning Attribute;Positron-Emission Tomography;Post-Acute Sequelae of SARS-CoV-2 Infection;post-COVID conditions;precision medicine;predictive modeling;programs;Proteins;receptor;Recording of previous events;Recovery;Registries;Reporting;Research;Research Infrastructure;Research Personnel;Research Priority;Resources;response;Rest;Risk;Risk Factors;SARS-CoV-2 infection;Science;Services;Severities;Standardization;Structure;Study models;Symptom Burden;Symptoms;System;systemic inflammatory response;targeted treatment;Testing;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Genetic predictors, pathophysiological mechanisms, and functional consequences of post-acute sequelae of SARS-CoV-2: Exercise challenge of gut microbiome and neuroinflammation in PASC


ORG_CITY: EAST ORANGE

ORG_NAME: VA NEW JERSEY HEALTH CARE SYSTEM

ORG_STATE: NJ

PHR: An estimated 10-50% of patients develop poorly understood chronic symptoms after COVID-19 (PASC), which, for many, is phenomenologically similar to chronic multi-symptom illnesses (CMI). A meta-synthesis found patients with PASC have poor experiences with care. This is consistent with decades of research on CMI, which finds patients experience wide-spread dissatisfaction with care, resulting in low uptake of evidence- based treatments and poor health outcomes. We have led VA research efforts to improve care for Veterans with CMI which has identified three key factors that lead to positive experiences with care (termed Concordant Care). Despite strong evidence supporting this care approach, there are no interventions to train clinicians on these evidence-based practices for poorly understood conditions. The objective is to leverage this research on CMI to adapt and test if a clinician training to deliver using an evidence-based, Concordant Care approach improves VA clinicians engaging in recommended practices for Veterans with PASC.

PI_NAMEs: MCANDREW, LISA MARIE (contact);NUGENT, SHANNON

PROJECT_TERMS: acute COVID-19;Address;Adherence;arm;care outcomes;Caring;Chronic;Chronic Care;clinical phenotype;Clinical Trials;COVID-19;crosslink;design;Diagnosis;disability;Disabling;Education;Effectiveness;effectiveness evaluation;Evaluation;evidence base;Evidence based practice;Evidence based treatment;experience;Expert Opinion;Feeling;Focus Groups;Generations;Gulf War veteran;Health;health inequalities;improved;Inequity;Intervention;Interview;Knowledge;Lead;Mental disorders;Methods;Military Personnel;military veteran;Mission;operation;Outcome;Patient Care;Patient Education;patient oriented;Patients;Pattern;Persian Gulf Syndrome;persistent symptom;phenomenological models;Phenotype;poor health outcome;Positioning Attribute;Post-Acute Sequelae of SARS-CoV-2 Infection;prevent;primary care clinician;Process;programs;Publishing;Randomized;randomized, clinical trials;Recommendation;Reporting;Research;SARS-CoV-2 infection;SARS-CoV-2 infection history;satisfaction;symposium;symptomatology;Symptoms;Testing;Training;uptake;user centered design;Veterans;whole health;Work

PROJECT_TITLE: Leveraging Knowledge of Chronic Multisymptom Illness to Improve Care for Veterans


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

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: The focus of our work is to determine how mutations carbohydrate aggregates impact multiple neurological diseases and to translate this knowledge into therapies. Our proposal is built on our past discoveries and uses complementary approaches to advance our understanding of the intertwined events of cell metabolism, neurodegeneration, and neurological disease. Completion of this work will yield a better comprehension of these complex events and will allow us to translate our insights into disease mechanisms, diagnoses, and treatments.

PI_NAMEs: GENTRY, MATTHEW S. (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Adolescence;Affect;Alzheimer's Disease;Ataxia;autosome;Behavior;Biochemical;Biology;biomarker development;Brain;brain metabolism;Carbohydrates;Cell Physiology;Cellular Metabolic Process;Cessation of life;Cognition;Complex;Comprehension;Consumption;Data;Development;Diagnosis;Disease;Disease Progression;driving force;Event;Excision;flexibility;Freedom;Funding;Glucose;glucose metabolism;Glycogen;glycogen metabolism;Glycogen Storage Disease;Homeostasis;human disease;insight;Intractable Epilepsy;Knowledge;Lafora Disease;Memory;Metabolic;Metabolism;Modality;Modeling;Molecular;mouse model;Mutation;National Institute of Neurological Disorders and Stroke;Nerve Degeneration;Nervous System Disorder;novel therapeutics;Patients;Play;polyglucosan;pre-clinical;Research;Role;Seminal;sex;Signal Transduction;Symptoms;Therapeutic;therapy development;Tissues;tool;Translating;Vegetative States;Work

PROJECT_TITLE: Brain Glycogen-Metabolism,Mechanisms, and Therapeutic Potential


NIH_SPENDING_CATS: Aging

ORG_CITY: NOVATO

ORG_NAME: BUCK INSTITUTE FOR RESEARCH ON AGING

PHR: PROJECT NARRATIVE The US population of elderly people is rapidly growing and age-related diseases constitute a major health issue in our society; however, the cellular and molecular basis of aging and age-related disorders is poorly understood. This proposal aims to determine how autophagy – a cellular process of cytoplasmic degradation with major biological functions – modulates organismal aging. The proposed research has relevance to public health, because the mechanisms to be investigated are evolutionary conserved and the findings might ultimately provide therapies to treat aging-related diseases.

PI_NAMEs: HANSEN, MALENE  (contact)

PROGRAM_OFFICER_NAME: OROSZ, ANDRAS

PROJECT_TERMS: Address;Adult;Affect;age-related disease;Aging;aging related;aging related disease;Animals;Autophagocytosis;Autophagosome;Binding;Biochemical;Biological Assay;Biological Process;Caenorhabditis elegans;Cell Physiology;cell type;Cells;combat;Complex;Cytology;Cytoplasm;Data;Development;Distal;Elderly;experimental study;extend lifespan;fitness;Follow-Up Studies;Genes;Genetic;genetic approach;Health;healthspan;Heat-Shock Response;Homologous Gene;Human;Immunoprecipitation;improved;in vivo;innovation;insight;Knowledge;Life;life span;Longevity;Mammalian Cell;mature animal;Mediating;Membrane;Mitochondria;model organism;Modeling;Molecular;mutant;Nematoda;Neurodegenerative Disorders;Neurons;novel;novel therapeutic intervention;Organism;overexpression;Persons;Play;Population;Positioning Attribute;Process;promoter;protein aggregation;Protein Isoforms;Proteins;proteostasis;Public Health;receptor;recruit;Recycling;Regimen;Regulation;Reporter;Reporting;Research;response;RNA Interference;Role;screening;Signal Transduction;Site;Societies;stress granule;Techniques;Testing;Time;Tissue Differentiation;Tissues;Vesicle;vesicular release

PROJECT_TITLE: Role of Selective Autophagy in Organismal Health

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


ED_INST_TYPE: SCHOOLS OF EDUCATION

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it investigates a potential new risk factor for cognitive decline, seeks to understand the underlying pathophysiology, and has high relevance to brain health. Upon completion, we will understand the impact of cerebral anatomical variations on cerebrovascular and cognitive health and its association with cognitive decline. The project is relevant to NIH’s mission because it will provide fundamental knowledge about brain health in humans and reduce disability associated with cognitive impairment.

PI_NAMEs: BARNES, JILL NICOLE (contact)

PROJECT_TERMS: Acute;Address;Adult;Aerobic Exercise;Affect;Age;age related changes;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Anatomy;Architecture;Biological Markers;Blood flow;Blood Pressure;Blood Vessels;Brain;brain health;cerebral hypoperfusion;Cerebrospinal Fluid;cerebrovascular;Cerebrovascular Circulation;cerebrovascular health;cerebrovascular reactivity;Cerebrovascular system;Cerebrum;Chronic;Clinical;clinically relevant;Cognition;Cognitive;cognitive testing;cohort;Compensation;Complex;Data;Development;disability;Early identification;effective intervention;Exhibits;Functional disorder;Genetic;Goals;Health;High Prevalence;high risk;Human;hypoperfusion;Hypoxia;imaging modality;imaging study;Impaired cognition;improved;Individual;Investigation;Knowledge;Link;Magnetic Resonance Imaging;Mediating;Medical;middle age;Mission;Modeling;neuroimaging;novel;older adult;Patient Recruitments;Perfusion;Physiological;Pre-Clinical Model;Process;Public Health;Publishing;Recommendation;Regional Perfusion;Regulation;Reporting;Research;response;Rest;Risk;Risk Factors;Stimulus;Subgroup;Techniques;United States National Institutes of Health;Universities;Variant;Vascular Dementia;vertebral artery;Wisconsin

PROJECT_TITLE: Impact of cerebral anatomical variations on cerebral perfusion, cerebrovascular reactivity, and biomarkers of cognitive decline

STUDY_SECTION: CICS

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


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);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Cerebrovascular;Dementia;Genetics;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: FARMINGTON

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

PHR: Defects in RNA-binding splice factors, prominently including TDP-43, contribute to Alzheimer’s Disease (AD) and the AD Related Dementia (ADRD) of Frontal Temporal Lobe Dementia; although neurons have been the primary focus of work in this field, our data suggests that reduced nuclear TDP-43 in endothelial cells of the BBB leads to leak, microvascular dysfunction and cognitive decline. Here, we assess splice factor function in the human BBB endothelium with age and in AD and ADRD, and test the consequences of these defects on BBB function. Our findings will reveal how alterations in TDP-43 and other endothelial RNA-binding proteins contribute to AD and ADRD, potentially providing a readily accessible target to slow disease progression.

PI_NAMEs: MURPHY, PATRICK ANDRIES (contact)

PROJECT_TERMS: Affect;Age;age related;Aging;Alternative Splicing;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Amyotrophic Lateral Sclerosis;Animal Model;APP-PS1;Bioinformatics;Blood;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Cells;Blood Platelets;Blood Vessels;blood-brain barrier function;Brain;brain cell;brain endothelial cell;brain tissue;Cell Nucleus;Cells;Cerebral endothelium;cognitive function;CRISPR screen;Cytoplasm;Data;Defect;Dementia;Disease;disease model;Disease Progression;Endothelial Cells;Endothelium;Event;Fibroblasts;Freezing;Frontotemporal Dementia;Frontotemporal Lobar Degenerations;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;Genes;Genetic;Genetic Models;Genetic Transcription;glial activation;Hemorrhage;hnRNP A1;Human;human model;Immune;immune activation;Immune response;Impaired cognition;Impairment;In Vitro;in vivo;Inflammation;Informatics;insight;Link;Maintenance;Mediating;Messenger RNA;Methods;Microglia;Microvascular Dysfunction;Modeling;mouse model;mRNA Precursor;Mus;Mutate;Mutation;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;Neurologic Dysfunctions;Neuronal Dysfunction;Neurons;neurovascular;neurovascular coupling;novel;novel strategies;Nuclear;Pancreas;Patients;Play;Post-Transcriptional Regulation;posttranscriptional;programs;protein function;Protein Isoforms;protein TDP-43;recruit;response;restoration;RNA;RNA Binding;RNA Splicing;RNA-Binding Proteins;Role;Sampling;screening;Sterility;Stream;TDP-43 aggregation;Techniques;Temporal Lobe;Testing;tool;Work

PROJECT_TITLE: Contributions of Endothelial RNA-binding Protein Dysregulation to Blood Brain Barrier Defects and Neurodegenerative Disease


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cardiovascular;Cerebrovascular;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: Project Narrative Age-related cognitive decline and dementia put an increasingly heavy burden on patients, families, and communities, and may be slowed or in many cases preventable if the key mechanisms can be identified. One of such mechanisms can be the life-time arterial vascular impacts on cerebral white matter, the portion of the brain connecting different brain regions. This study will track the lifespan relationships between several vascular functional mechanisms and white matter lifespan changes, to identify the key mechanisms that may aid prevention efforts against vascular contributions to cognitive impairment and Alzheimer's disease and promote normal, successful aging.

PI_NAMEs: HONG, L ELLIOT ELLIOT;KOCHUNOV, PETER V.;MITCHELL, BRAXTON D (contact)

PROJECT_TERMS: 3-Dimensional;abeta accumulation;Adolescence;Age;age effect;age related;age related decline;Age-associated memory impairment;Aging;aging brain;Alcohol consumption;allostatic load;Alzheimer's Disease;Alzheimer's disease risk;Amish;Anatomy;arterial spin labeling;arterial stiffness;Automobile Driving;Biological Markers;Biology;Blood Vessels;Brain;Brain imaging;Brain region;cardiometabolic risk;cardiovascular risk factor;Cardiovascular system;Cerebrovascular Circulation;Cerebrum;Clinical;Cognition;cohort;Cohort Effect;Collaborations;Communities;connectome;Coupling;Data;Dementia;Development;Diffusion Magnetic Resonance Imaging;effective therapy;endothelial dysfunction;Endothelium;Family;follow-up;Functional disorder;Genetic;Goals;Health;human old age (65+);Image;imaging modality;Imaging Techniques;Impaired cognition;indexing;Individual;insight;Label;Lesion;life span;Life Style;Measures;Mediating;Medicine;Mennonite;Modeling;Multimodal Imaging;Multivariate Analysis;Natural History;neuroimaging;Neurologic;novel;Organ;Pathogenesis;Pathway interactions;Patients;Pattern;Perfusion;Physiologic pulse;Policies;Population;prevent;Prevention;Prevention program;Process;Productivity;reactive hyperemia;Regional Disease;Research;Risk;Risk Factors;risk prediction;Risk Reduction;Rural;Scientist;Specificity;structural imaging;Structure;Testing;Tobacco use;United States National Institutes of Health;Vascular Cognitive Impairment;Vascular Endothelium;Vasodilation;white matter;white matter change;White Matter Hyperintensity;young adult

PROJECT_TITLE: Lifespan Vascular Biology on White Matter


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);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Neurodegenerative;Neurosciences

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: This proposal is the first attempt to address the role of post-translational modification of neuronal type2 ryanodine receptor (RyR2) as a potential contributing factor in amyloid-β (Aβ) depositions and disruption of intracellular calcium homeostasis that contributes to cognitive dysfunction in Alzheimer’s disease (AD). Our proposal also introduces a novel therapeutic approach to AD using a new class of orally available small molecule Rycal drugs that target intracellular calcium leak.

PI_NAMEs: MARKS, ANDREW ROBERT (contact)

PROGRAM_OFFICER_NAME: MCGAVERN, LINDA

PROJECT_TERMS: 3xTg-AD mouse;abeta deposition;Ablation;Address;Adrenergic Agents;adrenergic stress;Affect;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease therapeutic;Amyloid;APP-PS1;aspartate receptor;Behavioral;Binding;Biochemical;Biological Assay;Biological Markers;Brain;Ca(2+)-Transporting ATPase;calbindin;Calcium;Calcium Channel;Calcium Signaling;calmodulin-dependent protein kinase II;Calpain;cell type;Cells;Chronic;Clinical Trials;Cognition Disorders;Cognitive;cognitive function;Consensus;Cyclic AMP-Dependent Protein Kinases;Cytoplasm;Dantrolene;Data;Development;Dissociation;Drug Targeting;Drug usage;effective therapy;Endoplasmic Reticulum;Enzymes;Etiology;familial Alzheimer disease;FKBP1B gene;Functional disorder;Genetic;genetic approach;Glutamate Receptor;Goals;Hippocampus;Histopathology;Homeostasis;Human;Human Genetics;Hydroxyl Radical;Impaired cognition;improved;inorganic phosphate;Inositol;Isoxazoles;ITPR1 gene;Knock-in;Knock-in Mouse;Laboratories;Learning;Link;Long-Term Depression;Long-Term Potentiation;Malignant hyperpyrexia due to anesthesia;Mediating;Mediator;Memory;Memory Loss;Molecular Probes;mouse model;Mus;N-Methylaspartate;Neurodegenerative Disorders;Neurons;neuropathology;new therapeutic target;novel;novel drug class;novel therapeutic intervention;Oral;oxidation;Oxidative Stress;Parvalbumins;Pathogenesis;Pathologic;Pathway interactions;Performance;pharmacologic;Phosphorylation;Phosphorylation Site;Play;PMCA1 protein;Post-Translational Protein Processing;Post-Traumatic Stress Disorders;premature;preservation;prevent;Propionates;Protein Isoforms;receptor;Reporting;Rest;restraint stress;Role;Ryanodine Receptor Calcium Release Channel;Sarcoplasm;Senile Plaques;Signal Transduction;small molecule;Sodium-Calcium Exchanger;Source;Stress;Structure;synaptic function;Synaptic plasticity;Synaptic Transmission;Testing;Therapeutic;Therapeutic Effect;voltage;Work

PROJECT_TITLE: Calcium and the Pathophysiology of Neurodegenerative Disorders


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;Dementia;Down Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: The blood-brain barrier (BBB) tightly regulates the ﬂow of factors from the blood into the brain. Breakdown of the BBB has been associated with cognitive decline and Alzheimer's disease, but the molecular mechanisms linking BBB dysfunction with Alzheimer's disease are not fully understood. Genetic studies of Alzheimer's disease have implicated a set of genes that are active in cells of the BBB. Here, we will use an entirely human experimental system to determine the function and mechanisms of action of these genes.

PI_NAMEs: YOUNG-PEARSE, TRACY L (contact)

PROJECT_TERMS: 3-Dimensional;abeta accumulation;Abeta clearance;Address;Affect;Aging;Alzheimer's Disease;Alzheimer's disease risk;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Animal Model;Apolipoprotein E;apolipoprotein E-2;apolipoprotein E-4;Archives;Astrocytes;Binding;Biological Assay;Biological Models;Blood;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Vessels;blood-brain barrier function;Brain;brain endothelial cell;Cells;cerebral microvasculature;Clinical;cohort;Collaborations;Collection;Complement;Development;differentiation protocol;Dose;Down's Syndrome;Early Onset Alzheimer Disease;Electrical Resistance;Embryo;Endothelial Cells;Endothelium;Excision;Failure;Family;Functional disorder;Generations;Genes;Genetic;genetic risk factor;Genetic study;genetic variant;Health;Human;human induced pluripotent stem cells;human subject;Hypoxia;immunocytochemistry;Impaired cognition;Impairment;improved;in vitro Model;in vivo;Individual;induced pluripotent stem cell;insight;Late Onset Alzheimer Disease;Learning;Link;Measurement;Mediating;member;Memory;Metabolic Clearance Rate;Microfluidics;Modeling;Molecular;monomer;Morphology;mouse model;Mus;Mutation;Neurons;Organ;organ on a chip;Pathogenesis;Pathologic;Pathway interactions;Patients;Pericytes;Permeability;Physiological;Physiology;Play;Process;Proteomics;receptor;religious order study;Risk;risk variant;Role;Route;Series;shear stress;Signal Pathway;System;Technology;Toxic effect;transcriptome sequencing;transcytosis;uptake;Variant;Work

PROJECT_TITLE: Cell and Molecular Consequences of Alzheimer's Disease Genetic Variants on BBB Integrity and Function


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;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: CAMBRIDGE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: HARVARD UNIVERSITY

PHR: Narrative Declining brain vasculature is a key, but understudied, component of several age – associated neurodegenerative disorders including Alzheimer’s disease (AD) and related dementias. The research described in this proposal uses a combination of bioinformatics, mouse studies and human pluripotent stem cell modeling to identify and characterize novel AD-related pathways and factors involved in the maintenance or deterioration of blood vessels and the blood-brain barrier. Identifying factors that slow or reverse the decline of brain vasculature could be a new therapeutic avenue for these devastating and deadly disorders.

PI_NAMEs: RUBIN, LEE L (contact)

PROJECT_TERMS: abeta accumulation;Affect;age related changes;age related neurodegeneration;aged;Aging;aging process;aging related;Alleles;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Amyloid Beta A4 Precursor Protein;Animal Model;Astrocytes;base;Bioinformatics;biological adaptation to stress;Blood;Blood - brain barrier anatomy;Blood Vessels;Brain;brain cell;brain endothelial cell;brain parenchyma;Cell Communication;Cell Surface Receptors;cell type;Cells;cerebrovascular;Cerebrovascular system;Coculture Techniques;Data;Data Set;Defect;Dementia;dementia risk;Derivation procedure;Deterioration;Development;differentiation protocol;Disease;disease phenotype;Endothelial Cells;Equilibrium;Evaluation;experimental study;extracellular;Functional disorder;Gene Expression;Genes;Genetic;Genetic Diseases;Genetic Transcription;Health;Health Care Costs;Hippocampus;Human;human induced pluripotent stem cells;human model;human pluripotent stem cell;improved;In Vitro;in vitro Model;in vivo;Individual;induced pluripotent stem cell;intercellular communication;Knowledge;Ligands;Literature;Maintenance;Mediating;Modeling;Modification;Molecular;mouse model;Mus;Natural regeneration;nerve stem cell;Neurodegenerative Disorders;Neurons;neutralizing antibody;novel;novel therapeutic intervention;novel therapeutics;Nutrient;old mice;Oxidative Stress;Pathogenicity;Pathway interactions;Pericytes;Peripheral;pharmacologic;Phenotype;Process;Proliferating;Property;Protocols documentation;Publishing;Recombinant Proteins;Rejuvenation;Research;Role;Signal Pathway;Signal Transduction;Signaling Molecule;single cell sequencing;single-cell RNA sequencing;Smooth Muscle Myocytes;stem cell model;Stress;System;Testing;Time;timeline;transcriptomics;Vascular Diseases;Vascular regeneration;Vascular Smooth Muscle;Work

PROJECT_TITLE: Identifying and Correcting Dementia-Associated Changes in the Blood-Brain Barrier