NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Kidney Disease;Precision Medicine

PHR: PROJECT NARRATIVE The Minnesota-KPMP will recruit and follow-up study participants with chronic kidney disease due to diabetes or hypertension, the most common causes of chronic kidney disease, plus participants with type 1 diabetes who do not have clinical manifestations of kidney disease despite long diabetes duration. Underserved and underrepresented populations are disproportionately affected by chronic kidney disease, and the Minnesota- KPMP will engage a diverse patient population to evaluate and address barriers to enrollment in KPMP and to elicit the perspectives of our local participants on ethical issues posed by the KPMP, such as return of results and biobank governance. In a highly diverse metropolitan area actively confronting racism and disparities, this will add significantly to KPMP community engagement and ethics.

PI_NAMEs: CARAMORI, MARIA LUIZA A;NACHMAN, PATRICK H (contact)

PROGRAM_OFFICER_NAME: GIPSON, DEBBIE SUE

PROJECT_TERMS: Address;Adherence;Adult;Affect;Albumins;anti-racism;Area;biobank;Bioethics;biomedical informatics;Biopsy;Biopsy Specimen;Chronic Kidney Failure;Clinic;Clinical;Clinical Data;Clinical Sciences;Clinical Trials;Collaborations;Communities;community advisory board;community based participatory research;community engagement;Consent;Data;data access;Databases;Diabetes Mellitus;Diagnosis;disease heterogeneity;disorder prevention;Disparity;Electronic Health Record;Eligibility Determination;End stage renal failure;Enrollment;Ensure;Ethical Issues;Ethicists;Ethics;ethnic diversity;Excretory function;experience;Filtration;follow-up;Follow-Up Studies;genetic testing;Glomerular Filtration Rate;Goals;Health;Heterogeneity;Human;Hypertension;Impairment;implementation facilitation;Informatics;Insulin-Dependent Diabetes Mellitus;interest;Intervention;Kidney;kidney biopsy;Kidney Diseases;kidney dysfunction;Kidney Transplantation;Lesion;Light;Longitudinal Studies;Measures;member;metabolomics;Methods;metropolitan;mHealth;Minnesota;Mission;Molecular;Morbidity - disease rate;mortality;novel;Pancreas Transplantation;Participant;Pathologist;Pathway interactions;patient population;Patient Recruitments;Patient Representative;Patients;Phenotype;Population;precision medicine;Proteomics;Protocols documentation;racism;radiologist;randomized, clinical trials;recruit;Research;Research Methodology;Research Personnel;research study;resilience;Risk;Safety;Services;Siblings;Site;Specialist;success;Tissues;transcriptomics;Translational Research;Transplant Recipients;type I and type II diabetes;Underrepresented Populations;Underserved Population;Universities;urinary;Work

PROJECT_TITLE: Minnesota Precision Medicine CKD & Resilient Diabetes Recruiting Site: Engagement, Enrollment & Ethics


ADMINISTERING_IC: TW

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cardiovascular;Heart Disease;Nutrition;Prevention;Social Determinants of Health

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_FIPS: US

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE Cardiovascular disease prevention in Central America requires understanding how social determinants and place-based factors influence cardiovascular risk across the lifespan. It is critical to train and mentor the local workforce in identifying research questions relevant to CVD prevention, in the use of appropriate research methods to answer them, and in the dissemination of results to the scientific community, the public, and policy makers. Building on an established collaboration between INCAP and Drexel University, our training program will develop the research capabilities of trainees from the region and to build local capacity in the conduct of policy-relevant research on social determinants of cardiovascular risk across the lifespan.

PI_NAMEs: DIEZ ROUX, ANA VICTORIA;SANCHEZ, BRISA N (contact)

PROGRAM_OFFICER_NAME: LEVINTOVA, MARYA

PROJECT_TERMS: Americas;Applications Grants;Cardiovascular Diseases;cardiovascular disorder risk;Central America;Central American;Cities;Collaborations;Communities;Country;Data Analytics;data management;Development;Doctor's Degree;doctoral student;Educational workshop;Elements;Epidemiologic Methods;Faculty;Healthcare Systems;Incidence;Income;Inequity;Information Dissemination;interdisciplinary approach;Interdisciplinary Study;Intervention;Journals;Lead;Life course epidemiology;Life Cycle Stages;life span;Mentors;Mentorship;Methods;mid-career faculty;Neighborhoods;nutrition;Panama;Periodicals;Persons;Phase;Policies;Policy Maker;Postdoctoral Fellow;Prevalence;prevent;programs;Public Health;Publications;Research;Research Methodology;Research Personnel;Risk Factors;Site;social;social determinants;social health determinants;social influence;Students;Training;Training Activity;Training Programs;Translational Research;Translations;Universities;Urbanization;Visit;webinar

PROJECT_TITLE: Social determinants of cardiovascular disease risk over the life course

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


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: This research is aimed at understanding whether vasomotor symptoms and sleep problems, major symptoms of menopause, are associated with declines in cognitive and brain health over time in women. Findings from this study can improve the understanding of the role of these symptoms in the pathophysiology of Alzheimer's Disease (AD) and cognitive decline in women. They can point to female-specific markers that, if treated, may ultimately be able to be used to improve cognition, enhance brain reserve, and reduce the risk for AD in women.

PI_NAMEs: MAKI, PAULINE M;THURSTON, REBECCA C (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Acceleration;actigraphy;Adult;Affect;Age;Aging;aging brain;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Ambulatory Monitoring;Apolipoproteins;Atherosclerosis;Back;Basic Science;Benign;Blood;Brain;brain health;Brain imaging;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Carotid Atherosclerotic Disease;Cognition;Cognitive;cognitive change;cognitive function;cognitive performance;cognitive testing;cohort;Complex;cost;Data;Dementia;Diagnosis;Disease;Disproportionately impacts women;Early Intervention;Enrollment;Estradiol;Estrogens;Estrone;Event;Female;Functional disorder;Funding;Goals;Gonadal Steroid Hormones;Health;high risk;High Risk Woman;Hippocampus;Hormonal;Hormonal Change;Impaired cognition;improved;lifetime risk;Link;longitudinal design;Magnetic Resonance Imaging;Measurement;Measures;meetings;member;Memory;men;Menopausal Symptom;Menopause;middle age;Midlife women;mild cognitive impairment;Mitochondria;Morphology;Natural History;neuropathology;Neuropsychological Tests;Neuropsychology;novel;older women;Outcome;Participant;Performance;persistent symptom;Physiological;poor sleep;Postmenopause;recruit;Reporting;Research;Rest;Risk Factors;Risk Reduction;Role;Sampling;Science;sex;Sleep;Sleep Disorders;Sleep disturbances;sleep health;Structure;Symptoms;Testing;Time;Ultrasonography;ultrasound;vasomotor symptoms;Venous blood sampling;White Matter Hyperintensity;Woman;Work

PROJECT_TITLE: Menopausal Vasomotor Symptoms and Brain Aging in Women

STUDY_SECTION: APDA

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


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

ORG_CITY: NOVATO

ORG_NAME: BUCK INSTITUTE FOR RESEARCH ON AGING

ORG_STATE: CA

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on developing a new and alternative strategy to treat Alzheimer’s disease (AD) by eliminating senescent astrocytes that contribute to inflammation and neurodegeneration. We will achieve this by determining the role of the glycolytic by-product methylglyoxal in driving astrocyte senescence and neurodegeneration in AD. These studies will develop novel therapeutic targets to inhibit cellular senescence in the brain and reduce the risk of AD.

PI_NAMEs: KAPAHI, PANKAJ  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: 3xTg-AD mouse;Advanced Glycosylation End Products;Age;age acceleration;age-related disease;Aging;Alleles;Alzheimer associated neurodegeneration;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;Amino Acids;Astrocytes;Automobile Driving;base;Brain;brain tissue;Cell Aging;Cellular Stress;Cerebrospinal Fluid;Clinical Trials;Coculture Techniques;cognitive function;Combined Modality Therapy;Data;Dementia;DNA;DNA Damage;Drug Metabolic Detoxication;Elderly;Excision;Failure;genetic manipulation;Glycolysis;Goals;Human;human induced pluripotent stem cells;improved;in vivo;Incidence;Individual;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;Inflammaging;Inflammation;Inflammatory;innovation;knockout animal;Knowledge;Lactoylglutathione Lyase;Link;Lipids;Mediating;Mediator;Metabolic;Metabolism;Microglia;Modeling;Molecular Target;mouse model;mutant;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neurons;new therapeutic target;novel;novel strategies;novel therapeutics;Nucleotides;Outcome;PARK7 gene;Parkinson Disease;Pathway interactions;Pharmaceutical Preparations;pharmacologic;presenilin-1;Proteins;Proteomics;proteotoxicity;Public Health;Pyruvaldehyde;Research;Risk Factors;Risk Reduction;Role;senescence;senescence associated secretory phenotype;senescent cell;Signal Pathway;Stress;tau Proteins;Tauopathies;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;Thioctic Acid;Tissues;Visualization;Work

PROJECT_TITLE: Methylglyoxal drives astrocyte senescence to mediate neurodegeneration in Alzheimer's disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-A(50)R]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cancer;Colorectal Cancer;Digestive Diseases;Microbiome;Orphan Drug;Pancreatic Cancer;Rare Diseases

ORG_CITY: DURANGO

ORG_DEPT: CHEMISTRY

ORG_NAME: FORT LEWIS COLLEGE

ORG_STATE: CO

PHR: PROJECT NARRATIVE The goal of this project is the mechanistic characterization of enzymes from the human gut microbiome that are involved in polyamine biosynthesis. This project is relevant to public health because polyamine production by gut microbes is associated with disease states such as colon and pancreatic cancer. Enhanced understanding of gut microbe polyamine biosynthesis will open new targets for drug design leading to new treatment options for patients with these cancers.

PI_NAMEs: MCFARLANE, JEFFREY S (contact)

PROGRAM_OFFICER_NAME: FRINCU, CRINA

PROJECT_TERMS: Adenosylmethionine Decarboxylase;Amines;Anabolism;anti-cancer therapeutic;Aspartate;aspartic semialdehyde;Bacterial Gene Expression Regulation;Bacteroides;Bacteroides fragilis;Biological Assay;Biological Process;Campylobacter;cancer cell;Carbon Dioxide;Carboxy-Lyases;Cell Proliferation;Cells;Clinical Trials;Clostridium;colon cancer progression;Colon Carcinoma;colorectal cancer treatment;commensal bacteria;Data;Decarboxylation;design;Development;Disease;DNA Repair;Drug Design;Drug Targeting;Enzyme Kinetics;enzyme pathway;enzyme structure;Enzymes;Future;Genes;Goals;gut bacteria;gut microbes;gut microbiome;Human;inhibitor;kinetic model;Kinetics;Life;Link;Malignant neoplasm of pancreas;Malignant Neoplasms;member;Metabolic Pathway;Microbial Biofilms;Minor;NADP;NADPH Dehydrogenase;new therapeutic target;norspermidine;Operon;Organism;Orthologous Gene;Oxidoreductase;Pathway interactions;Patients;Physical condensation;Polyamines;Process;Production;programs;Public Health;Putrescine;Role;S-Adenosylmethionine;Spermidine;Spermidine Synthase;Structural Models;Structure;therapeutic target;tumorigenesis;uptake;Variant;Vibrio;Work;X-Ray Crystallography

PROJECT_TITLE: Characterization of polyamine biosynthetic enzymes from human gut microbes associated with colon and pancreatic cancer


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Adolescent Sexual Activity;Behavioral and Social Science;Clinical Research;HIV/AIDS;Infectious Diseases;Pediatric;Pediatric - AIDS;Pregnancy;Prevention;Teenage Pregnancy;Women's Health Research

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because redressing the ethical and regulatory barriers to HIV research with pregnant adolescents is crucial to providing safe and effective treatment for prevention and treatment of HIV and coinfections in adolescents and their offspring. The proposed research is relevant to NIH’s mission to reduce the burdens of illness and disability, through development of clear ethical and regulatory guidance for the conduct of morally complicated HIV research crucial to effective prevention and treatment of HIV in adolescents. Rigorously developed guidance for the conduct of ethically complex research advances the NIH’s goal to promote scientific integrity and social responsibility in the conduct of science.

PI_NAMEs: DAY, SUZANNE LOUISE;LYERLY, ANNE DRAPKIN (contact)

PROGRAM_OFFICER_NAME: ROE, JOANAD'ARC C

PROJECT_TERMS: Address;Adolescence;Adolescent;Adult;Adult women;Advocacy;Advocate;Affect;Africa South of the Sahara;Area;Attention;Birth;burden of illness;Child;co-infection;Committee Members;Communities;community advisory board;Complex;Confusion;Consensus;Consent;design;Development;disability;Disparity;effective therapy;Empirical Research;Equity;Ethicists;Ethics;evidence base;experience;Face;Female Adolescents;fetal;Funding;Goals;Health;HIV;HIV Infections;HIV/AIDS;improved;Individual;Infection;International;Interview;maternal risk;member;Methodology;Minor;Mission;Morals;Morbidity - disease rate;mortality;National Institute of Allergy and Infectious Disease;neglect;offspring;pandemic disease;Parents;Policies;Pregnancy;pregnant;pregnant teen;Pregnant Women;prevent;Prevention;Prevention Research;Prevention strategy;Public Health;Published Comment;Qualitative Research;Recommendation;Research;Research Ethics Committees;Research Personnel;Resources;Risk;Safety;Science;Social Responsibility;Southern Africa;Sterile coverings;Surface;treatment research;treatment strategy;United States National Institutes of Health;Vertical Transmission;waiver;Woman;working group;young woman;Youth

PROJECT_TITLE: PHASES Adolescence

STUDY_SECTION: PPAH

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: CLEVELAND

ORG_DEPT: GENETICS

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Colorectal cancer is the second most common cause of cancer deaths in the United States, with 133,000 new cases and 50,000 deaths per year. Thus, it is of critical importance to understand how colorectal cancer progress and metastasize because it is the metastatic disease that kill patients. Here we propose to determine how have an abnormality (called a mutation) in a gene called PTPRT drive colorectal tumor progression and metastasis. Knowledge gained from these studies may lay a foundation to find new ways to treat this deadly disease.

PI_NAMEs: WANG, ZHENGHE  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: 3-nitrotyrosine;Alleles;Antibodies;Belief;Binding;Binding Proteins;Bioinformatics;C-terminal;cancer cell;Cancer Etiology;cancer type;Carbon;Carcinogens;Cell Line;Cells;cellular transduction;Cessation of life;colon cancer metastasis;colon cancer progression;Colon Carcinoma;colon tumorigenesis;Colonic Neoplasms;Colorectal;Colorectal Cancer;colorectal cancer progression;Colorectal Neoplasms;Data;Development;Disease;Enzymes;Epigenetic Process;Extravasation;Follow-Up Studies;Foundations;Frameshift Mutation;Genes;Genetic;Goals;HCT116 Cells;Head and neck structure;Human;In Vitro;in vivo;innovation;Invaded;Knock-in;Knock-in Mouse;Knock-out;Knockout Mice;Knowledge;Laboratories;Lung;Malignant Neoplasms;Melanoma;Membrane;metastatic colorectal;migration;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;Nature;Neoplasm Metastasis;nitration;Nitrogen;Nonsense Mutation;Oncogenic;Organoids;Ovarian;Oxygen;Patients;paxillin;Penetrance;PH Domain;Phenols;Phosphoric Monoester Hydrolases;Phosphotransferases;Phosphotyrosine;Play;Positioning Attribute;Predisposition;protein function;Protein Tyrosine Phosphatase;Proteins;Reader;receptor;Role;Science;Seminal;Signal Pathway;Signal Transduction;Specificity;Specimen;src Homology Region 2 Domain;Stomach;success;Tertiary Protein Structure;Testing;tumor;tumor growth;tumor progression;Tumor Promotion;Tumor Suppressor Proteins;tumor xenograft;Tumor-Derived;tumorigenesis;Tyrosine;United States

PROJECT_TITLE: Role of PTPRT in colon cancer progression and metastasis

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


NIH_SPENDING_CATS: Aging;Cancer;Diabetes;Genetics;Hematology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: INDIANAPOLIS

ORG_DEPT: PEDIATRICS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: NARRATIVE This proposal will assess how alteration of downstream pathways as a consequence of TET2 mutations in leukemia initiating cells and in mature myeloid cells contributes to leukemic transformation including clonal hematopoiesis.

PI_NAMEs: KAPUR, REUBEN  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acceleration;Acute;age related;Aging;Automobile Driving;biological adaptation to stress;Blood Cells;c-myc Genes;Cardiovascular Diseases;Cells;Cellular Stress;chronic infection;Clonal Expansion;cytokine;Data;Development;Diabetes Mellitus;Disease;DNA Sequence Alteration;DNMT3a;Elderly;Epidemiology;Epigenetic Process;Exhibits;exome sequencing;fitness;FLT3 gene;Functional disorder;Funding;Genes;Healthcare;Hematologic Neoplasms;Hematopoiesis;Hematopoietic stem cells;high risk;Human;Hyperglycemia;Incidence;Individual;Induction of Apoptosis;Inflammatory;leukemia;leukemia initiating cell;Leukemic Cell;leukemic transformation;leukemogenesis;MAP Kinase Gene;Mediating;Metabolic Diseases;mutant;Mutate;Mutation;Myeloid Cells;Myeloid Leukemia;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Older Population;Oncogenes;Oncogenic;p21 activated kinase;p38 Mitogen Activated Protein Kinase;Pathway interactions;Patients;PIK3CG gene;Preleukemia;prevent;Process;Production;Protein Biosynthesis;Research;Risk Factors;Role;self-renewal;Signal Pathway;Signal Transduction;Somatic Mutation;stem cell population;therapeutic target;transcriptome sequencing

PROJECT_TITLE: Role of p21 activated kinase in Leukemogenesis

STUDY_SECTION: MONC

STUDY_SECTION_NAME: Molecular Oncogenesis Study Section[MONC]


NIH_SPENDING_CATS: Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: Narrative The goal of this proposal is to determine how lineage-specific repressive epigenetic landscapes are established by pioneer and PRDM transcription factors to safeguard cell identity. The successful completion of our Aims will reveal novel mechanisms underlying lineage-specific Polycomb repression and likely open new avenues to manipulate cell fate by selectively repressing alternative regulatory programs, with potential future therapeutic applications in regenerative medicine.

PI_NAMEs: IWAFUCHI, MAKIKO  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Binding;Binding Sites;Biological Assay;Cell Differentiation process;Cell Reprogramming;cell type;Cells;ChIP-seq;Chromatin;Cleavage Under Targets and Release Using Nuclease;Complex;CRISPR interference;Data;Deposition;Development;disease model;Doxycycline;Endoderm;Endoderm Cell;Epigenetic Process;Event;Fibroblasts;Future;Gene Activation;Gene Expression;gene repression;Genes;genomic locus;Genomics;Germ Cells;Goals;Hepatocyte;HNF4A gene;Human;human pluripotent stem cell;Hybrid Cells;Impairment;imprint;improved;insight;Knowledge;Mediating;Methods;Micrococcal nuclease digestion of chromatin followed by sequencing;mouse development;novel;Nuclear Extract;Nucleosomes;permissiveness;Play;pluripotency;Polycomb;Positioning Attribute;PRC1 Protein;PRDM1 gene;Process;programs;recruit;Regenerative Medicine;Regulation;Repression;Role;Shapes;Signal Transduction;Site;Specific qualifier value;Technology;Testing;Therapeutic;Time;tool;transcription factor;transcriptome sequencing

PROJECT_TITLE: Dynamic regulation of lineage-specific Polycomb repressive landscapes by pioneer and PRDM transcription factors

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


ADMINISTERING_IC: EB

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Neurosciences

ORG_CITY: HADLEY

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF MASSACHUSETTS AMHERST

ORG_STATE: MA

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on developing a new and alternative strategy to create neural interfaces that simultaneously minimize the electrical, mechanical, and biological mismatch between artificial devices with the nervous system and provide a unique opportunity to achieve long-term, accurate, real-time, and large-scale neural recordings and stimulations free of the foreign body response. Once such strategies have been developed, there is the potential for a significant advance in understanding brain development, disorders, and related behaviors as well as precise treatments to clinical disorders. Thus, the proposed research is relevant to the part of NIH’s mission to seek fundamental knowledge of the nature and behavior of living systems and use it for reducing illness and disability.

PI_NAMEs: LIU, TINGYI  (contact)

PROGRAM_OFFICER_NAME: FALCONE, JESSICA

PROJECT_TERMS: Address;Alloys;Behavior;bioelectronics;Biological;Biological Sciences;Biology;biomaterial compatibility;Biomedical Engineering;Body Temperature;Brain;brain circuitry;brain computer interface;Brain Diseases;Brain imaging;brain tissue;Cerebrospinal Fluid;Chronic;Clinical;Collaborations;Communication;Conflict (Psychology);Data;density;design;Development;Devices;disability;Disease;elastomeric;Elastomers;electric impedance;Electronics;Engineering;Environment;experience;Face;Failure;flexibility;Foreign Bodies;Gallium;Geometry;Goals;hard metal;Hydrogels;Imaging Techniques;Immune response;Implant;implantation;in silico;In Vitro;in vitro Model;in vivo;in vivo Model;Inflammatory;Inflammatory Response;innovation;Innovative Therapy;insight;instrumentation;Intelligence;Interdisciplinary Study;interfacial;kinematics;Knowledge;Liquid substance;Longitudinal Studies;manufacture;Mechanics;Medical;melting;Melting Point Temperatures;Metals;Methodology;Mission;Monitor;Motion;multi-electrode arrays;Mus;nanofabrication;Nanotechnology;Nature;Nervous System;Nervous System Disorder;neural;neural implant;neuronal circuitry;Neurons;Neurosciences;Neurosciences Research;next generation;operation;Organism;Penetration;Performance;phase change;Physics;Physiological;Polymers;Positioning Attribute;Property;Public Health;Regenerative Medicine;Research;Research Design;Resolution;response;Role;Signal Transduction;Silicon;solid state;spatiotemporal;success;System;Techniques;Technology;technology platform;Time;Tissues;United States National Institutes of Health;Work

PROJECT_TITLE: Engineering of Stretchable Neural Interfaces Using Liquid Metals for Stable Electrical Communication and Adaptive Stiffness Transformation

STUDY_SECTION: BNVT

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


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Neurosciences;Substance Misuse

ORG_CITY: DALLAS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative The hormone FGF21 is strongly induced by ethanol in liver and acts on the brain to suppress further alcohol consumption and to maintain hydration. We postulate that through coordinate effects on brain, adipose tissue and liver, FGF21 plays a much broader role in protecting against the harmful effects of alcohol, including liver injury and hypothermia. The proposed studies will provide important insights into the mechanisms whereby FGF21 protects against ethanol-induced toxicity and aid in determining whether FGF21 can be harnessed pharmaceutically to treat alcohol abuse and its associated pathologies.

PI_NAMEs: KLIEWER, STEVEN A. (contact);MANGELSDORF, DAVID J

PROGRAM_OFFICER_NAME: WANG, JOE

PROJECT_TERMS: Adipose tissue;Alcohol abuse;Alcohol consumption;alcohol effect;alcohol exposure;alcohol response;Alcoholic liver damage;Alcoholic Liver Diseases;Alcohols;Automobile Driving;Body Temperature;Brain;Brown Fat;Central Nervous System;Clinical Trials;Collection;Consumption;Disease;Dose;drinking water;Economics;Ethanol;experimental study;fatty acid oxidation;FGF21 gene;fibroblast growth factor 21;Fructose;Genetic Transcription;Genetically Engineered Mouse;genome wide association study;Health;hepatoma cell;Hormones;Human;Hydration status;induced hypothermia;insight;knock-down;Knock-out;Knockout Mice;Life;Link;Liver;liver injury;Mediating;Metabolic Diseases;Mitochondria;Modeling;Mus;natural hypothermia;Nerve;Nervous System;Neurons;Neuropeptides;Neurotensin;Nonesterified Fatty Acids;novel therapeutic intervention;Pathology;Pathway interactions;pharmacologic;Pharmacologic Substance;Play;preference;prevent;protective effect;receptor;Regulation;Repression;response;Rodent;Role;Series;Stimulus;Stress;sugar;Sympathetic Nervous System;Testing;Thermogenesis;Tissues;Toxic effect;transcription factor;uncoupling protein 1;Water;Water consumption

PROJECT_TITLE: Coordinate Regulation of an Alcohol Protective Response by the Liver-derived Hormone FGF21

STUDY_SECTION: XNDA

STUDY_SECTION_NAME: Xenobiotic and Nutrient Disposition and Action Study Section[XNDA]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Drug Abuse (NIDA only);Genetics;Human Genome;Neurosciences;Opioid Misuse and Addiction;Opioids;Substance Misuse

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: Project Narrative This project aims to identify the relationships between genetically-defined subpopulations of cells in the brain and the functional roles they play in opioid self-administration. This is likely to provide insight into the neural basis of drug addiction and identify possible therapeutic targets for future studies.

PI_NAMEs: SJULSON, LUCAS L (contact)

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Autopsy;Brain;brain tissue;cell type;Cells;Drug Addiction;Electrophysiology (science);epigenomics;Future;Gene Expression Regulation;Human;in situ sequencing;in vivo;innovation;insight;Label;Link;Methods;multiphoton imaging;Mus;neural;Neurons;new therapeutic target;novel;Nucleus Accumbens;Opiate Addiction;Opioid;Optical Methods;optogenetics;Oral;Phase;Play;Role;Self Administration;Substance Use Disorder;Techniques;therapeutic target;transcriptomics

PROJECT_TITLE: Uncovering links between neuronal transcriptomic and functional profiles in opioid addiction


ADMINISTERING_IC: EY

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Climate-Related Exposures and Conditions;Eye Disease and Disorders of Vision

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative This project characterizes the extent to which deamidation promotes deleterious oxidation and dynamics that ultimately lead to cataract-related aggregation. Additionally, high-resolution structure determination of cataract- related aggregates, which can advise the design of aggregation therapeutics, will be pursued. Finally, a novel role of human S-crystallin as a last resort oxidative buffer will be investigated.

PI_NAMEs: ROCHA, MEGAN  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Affect;Age;age related;Alzheimer's Disease;Amyloid Fibrils;Anions;Asparagine;Aspartic Acid;Biological;biophysical properties;biophysical techniques;Blindness;Buffers;Cataract;Cataract Extraction;Cell Nucleus;Charge;Chemicals;Crystalline Lens;Crystallins;Cysteine;deamidation;Deposition;design;Development;dimer;Dimerization;Disease;disulfide bond;Disulfide Linkage;Disulfides;experimental study;Exposure to;Glutamic Acid;Glutamine;Goals;Health Services Accessibility;Healthcare;Homeostasis;Human;Huntington Disease;Hydrophobicity;Implant;inhibitor;innovation;insight;Investigation;Knowledge;lens;lens cortex;Life Cycle Stages;Link;Magic;Mass Spectrum Analysis;Metabolic;Methods;Monitor;novel;Operative Surgical Procedures;Organelles;oxidation;Oxidation-Reduction;Pattern;Persons;Play;Population;Post-Translational Protein Processing;Predisposition;Prevalence;prevent;protein aggregation;protein degradation;Protein Disulfide Isomerase;Protein Dynamics;Proteins;Proteomics;Radiation induced damage;Regulation;Research;Resolution;Role;Site;solid state nuclear magnetic resonance;Solubility;standard of care;stem;Structure;System;Techniques;Technology;Therapeutic;Ultraviolet Rays;Variant;Work

PROJECT_TITLE: Exploring Crystallin Deamidation as a Causative Agent of Cataracts


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE PTEN is the second most commonly altered tumor suppressor in human cancer but the full repertoire of its normal and tumor suppressive functions remains unclear, which is slowing down progress toward improving treatment strategies for a large segment of cancer patients. In preliminary studies we find that the phosphorylation status of the PTEN C-tail domain controls important tumor suppressive functions that provide protection against neoplastic transformation even when PI3K-PDK1-mTORC1 signaling is out of control. The proposed studies are highly significant because the insights gained will lay the foundation for development of new therapeutic interventions that will improve the clinical outcome of cancer patients with PTEN mutations.

PI_NAMEs: BAKER, DARREN  (contact)

PROGRAM_OFFICER_NAME: CERO, CHERYL

PROJECT_TERMS: Advanced Malignant Neoplasm;AKT Signaling Pathway;Alanine;Alleles;Antineoplastic Agents;Binding;Biological;Biological Process;Cancer Biology;Cancer Patient;Cells;Clinical;cohort;comparative;Cytoplasm;Development;Embryonic Development;Enzymes;Foundations;Generations;Genetically Engineered Mouse;Goals;Heterozygote;Homo;Human;Hyperactivity;improved;In Vitro;in vivo;Individual;innovation;insight;Knock-out;Knowledge;Lesion;Loss of Heterozygosity;lymphadenopathy;Malignant Neoplasms;Mammary gland;mimetics;Molecular Conformation;Monitor;mouse development;mouse model;Mouse Strains;Mus;mutant;Mutant Strains Mice;Mutate;Mutation;neoplastic;Neoplastic Cell Transformation;novel therapeutic intervention;Nuclear;Outcome;PDPK1 gene;Phosphoric Monoester Hydrolases;Phosphorylation;Physiological;Physiology;PIK3CG gene;Post-Translational Protein Processing;Predisposition;preservation;Property;Prostate;prostate lesions;Proteins;Proto-Oncogene Proteins c-akt;PTEN gene;Regulation;Role;Series;Serine;Signal Transduction;Systems Biology;Tail;Testing;Threonine;tissue/cell culture;Tissues;treatment strategy;tumor;Tumor Suppression;Tumor Suppressor Genes;Tumor Suppressor Proteins;tumorigenesis

PROJECT_TITLE: Regulation of pten tumor suppressive functions by C-tail phosphorylation.

STUDY_SECTION: CSRS

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


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

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE Dysregulated lipid metabolism is a hallmark of epithelial ovarian cancer, which is associated with widespread and rapid metastasis throughout the lipid rich abdominal cavity. A key fact is that epithelial ovarian cancer cells can metabolically reprogram themselves to use other energy sources, such as lipids and fat cells in the abdominal cavity, to sustain their incredibly fast growth, metabolic changes that also help them survive after chemotherapy. We hypothesize that EOC cells store energy in intracellular lipid droplets and under metabolic stress use this stored energy to fuel growth and invasive cell migration; this hypothesis will be explored using a novel 3D culture model to track metabolic changes in chemoresistant EOC cells as well as to study their lipid droplet metabolism and autophagy.

PI_NAMEs: DAWSON, MICHELLE R (contact)

PROJECT_TERMS: 3-Dimensional;Abdominal Cavity;Actins;Adipocytes;Affect;Animals;Ascites;ATP-G-actin;Autophagocytosis;Autophagosome;Biological Assay;biophysical analysis;Biosensor;cancer cell;cancer therapy;cell motility;Cell Survival;cell type;Cells;Cellular Metabolic Process;Chemoresistance;chemotherapy;Cytosol;Data;Development;Diagnosis;Disease;Disease Progression;Drug resistance;Energy Metabolism;Energy-Generating Resources;Ensure;Environment;Epithelial ovarian cancer;Fatty acid glycerol esters;fatty acid oxidation;Fatty Acids;Free Energy;Genetic;Genus Hippocampus;Glycolysis;Growth;Heterogeneity;high resolution imaging;Human;Hypoxia;In Vitro;in vivo Model;Individual;Inflammatory;inhibition of autophagy;inhibitor;Intermediate Filaments;lipid metabolism;lipid transport;Lipids;Lipolysis;Liquid substance;Lysosomes;Malignant Female Reproductive System Neoplasm;Measures;Mediating;Metabolic;Metabolic stress;Metabolism;metabolomics;Microspheres;migration;Mitochondria;Modeling;Molecular;Mus;Nature;Neoplasm Metastasis;neoplastic cell;new therapeutic target;Nonesterified Fatty Acids;novel;Nutrient;nutrient deprivation;Omentum;Organoids;Ovary;Oxidative Phosphorylation;paracrine;Pathway interactions;Peritoneal;Peritoneum;pharmacologic;Phenotype;polarized cell;polymerization;Polymers;Primary Neoplasm;Production;programs;Proteins;Reactive Oxygen Species;recruit;Research;Resistance;Role;scaffold;single-cell RNA sequencing;Small Interfering RNA;Source;Stress;Stromal Cells;Structure;Testing;Therapeutic;three dimensional cell culture;tumor;tumor growth;tumor heterogeneity;tumor metabolism;tumor microenvironment;tumor progression;Tumor Promotion;Vimentin

PROJECT_TITLE: Lipid Metabolism Switch Triggers Invasive and Chemoresistant Epithelial Ovarian Cancer Phenotype

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


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

ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE Activating ERBB2 mutations are enriched in invasive lobular carcinoma (ILC) of the breast, suggesting a crosstalk between ERBB2 mutations and the characteristic loss of CDH1 in ILC. Clinical trials have demonstrated promising efficacy using anti-HER2 tyrosine kinase inhibitors in patients with ERBB2 mutant ILC. The ultimate goal of the proposed studies is to characterize the functional roles of recurrent ERBB2 mutations in ILC vs IDC using innovative preclinical models and provide rationale for specific combination targeted therapy in patients with ERBB2 mutant ILC, in order to enhance anti-tumor activity and/or delay drug resistance.

PI_NAMEs: LIU, JIE BIN  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Acceleration;Antibody-drug conjugates;Automobile Driving;Breast;Cadherins;Cell Line;Characteristics;Clinical;Clinical Management;Clinical Trials;clinically relevant;clinically significant;Clustered Regularly Interspaced Short Palindromic Repeats;Combined Modality Therapy;Complement;Data;Dependence;Disease;Drug resistance;E-Cadherin;effective therapy;Engineering;Environment;Epidermal Growth Factor Receptor;ERBB2 gene;Estrogen receptor positive;Evolution;Exhibits;experimental study;FDA approved;Future;gain of function;Genes;Genetic Transcription;genome editing;Genomics;Goals;Growth;Growth Factor Receptors;Heat-Shock Proteins 90;Histologic;hormone therapy;HSP 90 inhibition;IGF1R gene;In Vitro;in vitro Model;Inferior;infiltrating duct carcinoma;innovation;Investigation;Knock-out;Learning;Lobular Carcinoma;Malignant Breast Neoplasm;Malignant Epithelial Cell;Mediating;Messenger RNA;Metastatic breast cancer;Molecular;Molecular Chaperones;mRNA Expression;mutant;Mutation;Nature;Nuclear;Null Lymphocytes;Oncogenic;Organoids;Outcome;overexpression;patient subsets;Patients;permissiveness;Phenotype;Physicians;Plasma;Pre-Clinical Model;Prevalence;Prognosis;protein expression;Receptor Protein-Tyrosine Kinases;Recurrence;Regulation;Reporting;Repression;Research Personnel;Resistance;response;Role;Sampling;Scientist;Signal Pathway;Signal Transduction;Specimen;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic;therapy resistant;Training;transcriptome sequencing;translational cancer research;tumor;tumor progression;Tyrosine Kinase Inhibitor;Woman;Xenograft procedure

PROJECT_TITLE: Characterizing and Targeting ERBB2 Mutations in Invasive Lobular Carcinoma


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Dietary Supplements;Mental Health;Microbiome;Neurosciences;Nutrition;Pediatric;Prevention

ORG_CITY: WASHINGTON

ORG_NAME: CHILDREN'S RESEARCH INSTITUTE

ORG_STATE: DC

PHR: Project Narrative: Women and children in sub-Saharan Africa who have a chronic dietary reliance on toxic cyanogenic cassava are at heightened risk for the development of cassava neurotoxicity, leading to a debilitating disease with severe physical and cognitive impairments known as konzo. While factors such as nutrition, toxicity dose, water access and other environmental factors are associated with the development of konzo, the exact molecular mechanisms that contribute to disease pathogenesis remain largely unknown, despite large global health significance. Here we aim to determine the likely modulatory role of the gut microbiome by elucidating differences in composition and functionality in regards to host-microbiome metabolism between disease discordant siblings, leading to a deeper understanding of susceptibility and potential monitoring and preventative solutions.

PI_NAMEs: BRAMBLE, MATTHEW SCOTT (contact)

PROGRAM_OFFICER_NAME: HAYES, UNJA

PROJECT_TERMS: Address;Adolescent;Affect;Africa South of the Sahara;bacterial community;beta-Glucosidase;Biochemical;Biochemical Pathway;Biological Markers;biomarker identification;career;career development;Cessation of life;Child;Child Development;Child Health;Chronic;Cognition;Consumption;Coupled;Cyanides;Data;Dedications;Democratic Republic of the Congo;Development;dietary;Discipline;Disease;Disease Outbreaks;Disease susceptibility;Dose;Drug Metabolic Detoxication;Educational workshop;Environment;Environmental Risk Factor;Enzymes;Fellowship;Fogarty International Center;Food;food insecurity;Future;gastrointestinal;Gene Expression Profiling;Genes;Genetic;global health;gut microbiome;gut microbiota;High Pressure Liquid Chromatography;HIV;host microbiome;Impaired cognition;Individual;insight;Intoxication;Knowledge;Low Prevalence;Malaria;Malnutrition;Manihot;Mass Spectrum Analysis;Maternal and Child Health;Mediating;Metabolic;Metabolism;metabolomics;metagenomic sequencing;Metagenomics;metatranscriptomics;Microbe;microbial composition;microbial signature;microbiome;Mission;Molecular;Monitor;Motor;motor deficit;Motor Neuron Disease;National Human Genome Research Institute;Neurocognition;Neurocognitive Deficit;Neurodevelopmental Deficit;Neuroepidemiology;Neuropsychological Tests;neurotoxicity;nutrition;Pathogenesis;Pathogenicity;Persons;physical impairment;Plants;Predisposition;Prevalence;Prevention;Prevention strategy;Process;Publishing;Research;Research Activity;Resources;Risk;Risk Factors;Role;Scientist;Severities;Severity of illness;sex;Siblings;Source;Spastic Paraparesis;stool sample;Structure;study population;Testing;Thiocyanates;Time;Toxic effect;Toxicology;Toxin;Training;transcriptome sequencing;transcriptomics;United States National Institutes of Health;Variant;Water;Woman;World Health Organization

PROJECT_TITLE: Modulatory Effects of the Functional Gut Microbiome in Relation to Cassava Associated Motor and Neurocognitive Deficits

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-ICP-L(57)R]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Clinical Research;Dietary Supplements;Health Services;Neurodegenerative;Neurosciences;Nutrition;Peripheral Neuropathy;Prevention

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Project Narrative Distal Symmetric Polyneuropathies (DSP) are highly prevalent among clinic populations in Zambia compared to other world regions and preventable nutritional and other treatable comorbidities are suspected to be contributing. Our study is designed to identify clinic- versus population-based risk factors for DSP in this setting. These studies will help define appropriate intervention targets for nutrition-associated neurologic morbidity in Zambia and frame future observational studies to identify complex pathogenic mechanisms involved in asymptomatic and symptomatic DSP development.

PI_NAMEs: KVALSUND, MICHELLE POWELL (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Adult;Africa South of the Sahara;Age;Area;axonopathy;care seeking;case control;chronic pain;Clinic;Clinical;Clinical Trials;Communicable Diseases;Communities;Community Health;comorbidity;comparative;comparison control;Complex;Data;design;Development;Diabetes Mellitus;Diagnostic;dietary;Dietary Factors;Dietary intake;Dietary Intervention;Distal;Environment;Epidemiologic Methods;Etiology;experience;Factor Analysis;falls;Folic Acid;Folic Acid Deficiency;Food;food insecurity;Foot Ulcer;Foundations;Functional disorder;Future;Gender;global health;Goals;Health care facility;health care settings;Health Policy;Healthcare;HIV;HIV Seronegativity;Homocysteine;Household;improved;Individual;Intervention;Intervention Studies;Knowledge;Lead;limb amputation;Link;Maize;Malnutrition;Manihot;Manuscripts;member;Mentorship;Metabolic;Methodology;micronutrient deficiency;Micronutrients;Modeling;Morbidity - disease rate;Nature;Neurologic;Neurologist;Neuropathy;neurotoxic;nutrient deprivation;nutrition;Nutritional;Observational Study;Outcome Assessment;Pathogenicity;Patient Care;Pattern;Peer Review;Persons;Phenotype;Plasma;Polyneuropathy;Population;Population Analysis;population based;Pragmatic clinical trial;Predisposition;Prevalence;Province;public health intervention;Quality of life;Random Allocation;Recurrence;regional difference;Research;Research Training;Risk;Risk Factors;Rural;rural residence;Sampling;Scientific Advances and Accomplishments;screening;sex;skills;Structure;Surveys;Thiamine;Thiamine Deficiency;Urbanicity;Validation;Vitamin B 12;Vitamin B 12 Deficiency;Zambia

PROJECT_TITLE: Community Health and Neuropathy: Nutritional and Environmental Links in Zambia (CHANNELZ)

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Drug Abuse (NIDA only);Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Substance Misuse

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: Project Narrative The proposed research is relevant to public health because it is aimed at developing and applying new approaches to understanding how mammalian subcortical brain circuits control evolutionarily conserved naturalistic social behaviors, which may be disrupted in human psychiatric disorders. Our objective is to construct better, high-resolution maps of neural activity dynamics in the brain during social behavior, by imaging from multiple brain sites in a circuit, and using machine learning algorithms (AI) to automatically extract and measure social behavior from video recordings, thereby enabling precise, quantitative correlations between distributed brain activity and behavior. We also propose to examine how intruder sex and behavioral decisions are computed and transformed as they are propagated through the network.

PI_NAMEs: ANDERSON, DAVID J (contact)

PROGRAM_OFFICER_NAME: DAVID, KAREN KATE

PROJECT_TERMS: Address;Aggressive behavior;Algorithms;Amygdaloid structure;Animals;Behavior;Behavior Control;Behavioral;behavioral response;Biological Models;Brain;Cell Nucleus;cell type;Cells;cellular targeting;Code;Computing Methodologies;Data;Decision Making;Encapsulated;Endoscopy;Equilibrium;experimental study;Female;Functional Imaging;Genetic;Goals;Human;Hypothalamic structure;Image;imaging study;in vivo;Individual;innovation;insight;Knowledge;Logic;Machine Learning;machine learning algorithm;machine learning classification;male;Maps;Measurement;Measures;Medial;Mental disorders;midbrain central gray substance;Midbrain structure;Modeling;Motivation;Mus;neural;neural circuit;neuroimaging;Neurons;neuroregulation;novel;novel strategies;optogenetics;Organism;Output;Partner in relationship;Phase;Phenotype;Population;Population Dynamics;predictive modeling;Preoptic Areas;programs;Property;Public Health;Reproduction;reproductive;Reproductive Behavior;Research;Resolution;Rewards;Role;sex;sexual identity;Shapes;Site;Social Behavior;Social Controls;Social Interaction;Structure;System;Testing;Video Recording;Work

PROJECT_TITLE: Circuit basis of social behavior decision-making in a subcortical network


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Human Genome;Prevention;Substance Misuse

ORG_CITY: ALBUQUERQUE

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: Project Narrative Alcohol use disorder and excessive drinking are significant public health issues with a genetic basis. Recent well-powered genome wide association studies have increasingly identified genetic variants that contribute to alcohol consumption in humans. This proposal will provide critical training in converging translational genetic research strategies for characterizing the role of novel candidate genes in alcohol use disorder and related behaviors.

PI_NAMEs: BARKLEY-LEVENSON, AMANDA MALINA (contact)

PROGRAM_OFFICER_NAME: LORANG-LEINS, DOMINIQUE

PROJECT_TERMS: Acute;addiction;alcohol consequences;Alcohol consumption;Alcohol dependence;alcohol effect;alcohol risk;alcohol use disorder;Alcohols;Animal Model;Animals;Behavior;behavior influence;behavior test;Behavioral;Behavioral Assay;Behavioral Paradigm;behavioral phenotyping;binge drinking;Biological;Blood alcohol level measurement;Candidate Disease Gene;Cell Adhesion Molecules;Chronic;Consumption;consumption measures;cost;Darkness;Data;Data Collection;Development;drinking;drinking behavior;endophenotype;Environmental Risk Factor;experimental study;follow-up;gene discovery;Genes;Genetic;genetic approach;genetic manipulation;Genetic Research;Genetic Risk;genetic variant;genome wide association study;genome-wide;genome-wide analysis;Genotype;Goals;Heavy Drinking;Heritability;Human;Human Genome;human model;Individual;innovation;insight;Intake;knockout animal;Knockout Mice;Knowledge;Literature;Maps;Measures;Methods;model organism;Modeling;Motivation;mouse genome;mouse model;Mus;Mutant Strains Mice;negative affect;new therapeutic target;novel;novel strategies;Organism;Pattern;pharmacologic;Phase;Phenotype;Population;Positioning Attribute;Prevention strategy;Public Health;Quantitative Genetics;Quantitative Trait Loci;Questionnaires;Research;Research Personnel;Rewards;risk variant;Role;Self Stimulation;Site;skills;societal costs;Societies;Statistical Methods;Structure;Testing;Training;trait;Translating;translational approach;translational genetics;vapor;Withdrawal;Work

PROJECT_TITLE: Identification and Characterization of Novel Genetic Mechanisms in Alcohol Use Disorder and Excessive Drinking


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: MINNEAPOLIS

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PROJECT NARRATIVE This project will scale (via a hybrid type 2 stepped wedge randomized effectiveness-implementation trial) and rigorously evaluate an interoperable clinical decision support system (CDS) across our collaborative CDS community for venous thromboembolism prevention. Via mixed-methods, we will study implementation guided by the EPIS implementation framework throughout scaling. Finally, we will pilot an approach for “Living Guideline” development and use that to update and sustain evidenced-based decision logic within a centrally- housed interoperable CDS knowledge repository.

PI_NAMEs: MELTON-MEAUX, GENEVIEVE B;TIGNANELLI, CHRISTOPHER J (contact)

PROGRAM_OFFICER_NAME: TERAN, MARIO

PROJECT_TITLE: Evaluation of the SCALED (SCaling AcceptabLE cDs) Approach for the Implementation of Interoperable CDS for Venous Thromboembolism Prevention

STUDY_SECTION: HITR

STUDY_SECTION_NAME: Healthcare Information Technology Research[HITR]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Eye Disease and Disorders of Vision;Networking and Information Technology R&D (NITRD);Neurosciences;Rehabilitation

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Program Director/Principal Investigator (Last, First, Middle): Baccus, Stephen A. The retina and primary visual cortex are complex networks of many cell types. We know little about how the visual cortex processes natural scene information, particularly in the context of behavior. By understanding a detailed a quantitative description of how visual experience is represented in the visual cortex, we will have a better understanding of how this process breaks down in diseases such as amblyopia, strabismus, dyslexia and schizophrenia. Furthermore, by capturing the responses of these neurons under natural visual stimuli with accurate computational models, this research will be immediately applicable to electronic cortical prosthesis systems that aim to restore vision in cases of loss of vision due to damage to the eye.

PI_NAMEs: BACCUS, STEPHEN A (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Affect;Amblyopia;area striata;awake;Bayesian Prediction;Behavior;Behavioral;Biophysics;Blindness;Brain;cell type;Cells;Code;Complex;Computer Models;Data;Detection;Disease;Dyslexia;Electronics;Electrophysiology (science);Environment;Esthesia;Ethology;experience;experimental study;Eye;Eye Movements;feature detection;Foundations;Goals;Head Movements;Health;Human;insight;Knowledge;Lead;Learning;Locomotion;Machine Learning;Measures;Memory;Modeling;Motion;Motor;Motor Activity;motor behavior;Movement;Mus;neural;neural model;Neurons;Neurophysiology - biologic function;nonhuman primate;object motion;Ocular Prosthesis;optic flow;Pattern;Population;Preparation;Primates;Principal Investigator;Probability;Process;programs;Property;Prosthesis;Research;response;Retina;Schizophrenia;sensory cortex;sensory input;sensory system;sight restoration;Signal Transduction;Silicon;Smell Perception;Speed;statistics;Stimulus;Strabismus;Stream;Structure;System;Testing;theories;Uncertainty;virtual reality;virtual reality system;Visual;Visual Cortex;visual information;visual processing;visual stimulus;Visual System

PROJECT_TITLE: Neural processing of natural scenes in the visual cortex

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: CLEMSON

ORG_NAME: CLEMSON UNIVERSITY

ORG_STATE: SC

PHR: NARRATIVE The proposed research is relevant to public health because it addresses mechanisms responsible for proliferation of Cryptococcus neoformans, which is a major fungal pathogen causing infection of the central nervous system in HIV/AIDS patients. C. neoformans requires septin proteins to respond to stress it encounters in the human host and the main goal of this proposal is to explain mechanisms through which septins contribute to pathogenicity. Our studies will help to identify better drug targets against cryptococcal infection in immunocompromised patients. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

PI_NAMEs: KOZUBOWSKI, LUKASZ  (contact)

PROGRAM_OFFICER_NAME: RADKE, JOSHUA BRYAN

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Alleles;Animals;Aspergillus nidulans;Binding;biophysical properties;Blood Circulation;Cell membrane;Cell Membrane Permeability;Cell Wall;Cells;Central Nervous System Infections;Cessation of life;Complex;Critical Pathways;Cryptococcosis;Cryptococcus;Cryptococcus neoformans;Cues;Cytokinesis;Data;Drug Targeting;Engineering;Exclusion;Exhibits;experimental study;Exposure to;Fatal Outcome;Filament;Fluconazole;fluidity;Fluorescence Microscopy;Foundations;Genes;Genetic;genetic approach;Goals;Growth;Guanosine Triphosphate Phosphohydrolases;High temperature of physical object;HIV;HIV/AIDS;Homeostasis;Human;Immunocompromised Host;improved;In Vitro;Infection;Inhalation;inhibitor;innovation;Inositol Phosphates;Knowledge;Life;Light;Link;Lipid Bilayers;lipid metabolism;Lipids;Lung;Maintenance;Mediator;Membrane;Membrane Fluidity;Membrane Lipids;Meningoencephalitis;model organism;Modeling;Monomeric GTP-Binding Proteins;mortality;Mus;mutant;novel;novel therapeutic intervention;Outcome;Pathogenesis;pathogenic fungus;Pathogenicity;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Phenotype;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Phospholipase C;Population;predictive modeling;prevent;Proliferating;Propidium Diiodide;protein complex;Protein Kinase C;Proteins;Public Health;Publishing;Recombinants;reconstitution;recruit;Research;response;Role;side effect;Signal Pathway;Signal Transduction;Sodium Dodecyl Sulfate;Sphingolipids;Sterols;Stress;Stress Response Signaling;Temperature;Temperature Sense;temperature sensitive mutant;Testing;thermozymocidin;Time;transmission process;Virulence

PROJECT_TITLE: The role of septins in the adaptation of Cryptococcus neoformans to host temperature in HIV-based cryptococcosis

STUDY_SECTION: HCAC

STUDY_SECTION_NAME: HIV Coinfections and HIV Associated Cancers Study Section[HCAC]


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

ORG_CITY: CHICAGO

ORG_DEPT: NEUROSCIENCES

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

ORG_STATE: IL

PHR: NARRATIVE Alzheimer’s disease is a complex disorder that impairs mobility and cognition in older adults, but often poor mobility may precede and predict Alzheimer’s dementia. Optimizing mobility as a biomarker and determining the pathologies and proteins which drive impaired mobility may explain why this phenotype predicts Alzheimer’s dementia. Targeting the drivers of impaired mobility can lead to new treatments that have the potential to prevent two of the most common concerns of older adults, immobility and Alzheimer’s dementia.

PI_NAMEs: BUCHMAN, ARON S (contact)

PROGRAM_OFFICER_NAME: ST  HILLAIRE-CLARKE, CORYSE

PROJECT_TERMS: Accelerometer;Adult;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Alzheimer's disease risk;Area;Attention;base;Biological Markers;brain control;Brain Pathology;Brain region;Cessation of life;clinical care;Cognition;Cognitive;cognitive ability;cognitive testing;Complement;Complex;Data;Dementia;digital;digital data;digital phenotyping;Disease;Early Onset Alzheimer Disease;executive function;Gait;Immobilization;Impaired cognition;Impairment;improved;improved mobility;indexing;Individual;Measures;Memory;Mobility decline;Motor;motor impairment;Movement;novel;older adult;Participant;Pathologic;Pathology;Phenotype;pre-clinical;Prefrontal Cortex;prevent;Prevention;Proteins;Proteome;Public Health;Research;Resources;Risk;Role;Sampling;sensor;Set protein;Subgroup;Testing;Thinking;Walking;Work;Wrist

PROJECT_TITLE: Thinking about walking: Can digital phenotyping of mobility improve the prediction of Alzheimer's dementia and inform on the pathologies and proteins contributing to this association?

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Digestive Diseases;Genetics;Inflammatory Bowel Disease;Physical Injury - Accidents and Adverse Effects;Prevention;Regenerative Medicine;Wound Healing and Care

ORG_CITY: LAWRENCE

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF KANSAS LAWRENCE

ORG_STATE: KS

PHR: NARRATIVE Ulcerative colitis is characterized by recurring bouts of mucosal tissue damage and regeneration. This project is expected to identify mechanisms by which nuclear Adenomatous polyposis coli protein promotes mucosal healing through wound repair and restoration of the protective mucus layer. Such knowledge would serve as the basis for future design of novel therapeutic strategies for UC and other IBDs aimed to enhance APC’s wound healing activities.

PI_NAMEs: NEUFELD, KRISTI L (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Acute;Address;American;Anti-Inflammatory Agents;APC gene;APC mutation;Automobile Driving;Binding;Biological Assay;Candidate Disease Gene;Cell Differentiation process;cell mediated immune response;Cell Nucleus;Cell Proliferation;Cells;chemokine;Chemotaxis;ChIP-seq;Chronic;Clinical;Clinical Treatment;Colitis;Colon;Colon Injury;Complex;cytokine;Cytoplasm;Data;design;Development;Diagnosis;Distal;Epithelial Cells;epithelial injury;epithelial repair;epithelial wound;Epithelium;Etiology;Future;Gene Expression;Generations;Genes;Genetic;Genetic Transcription;Goals;Goblet Cells;gut microbes;healing;Homeostasis;Human;human tissue;Immune response;In Vitro;in vivo;Individual;Inflammation;Inflammation Mediators;Inflammatory Bowel Diseases;Injury;injury and repair;injury prevention;Interleukin-1;Intervention;intestinal homeostasis;Intestines;Invaded;Irritants;Knock-in;Knowledge;Link;Lymphoid Follicle;Mediator;microbial;microbial composition;microbiota;mouse model;Mucin-2 Staining Method;Mucous body substance;Mucous Membrane;Mus;Mutation;Natural regeneration;neutrophil;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Nuclear;Nuclear Import;Pathologic;Patients;Penetration;Phenotype;Predisposition;prevent;Prevention;Process;Production;Proliferating;promoter;Publishing;Recovery;Recurrence;Reporter;Reporting;Research;response;restoration;Role;Signal Pathway;Signaling Protein;single-cell RNA sequencing;Small Interfering RNA;Sodium Dextran Sulfate;Stains;symptom management;Testing;Therapeutic;Thick;Time;tissue injury;tissue repair;Tissue Sample;Tissues;Transcriptional Regulation;transcriptome sequencing;Translating;treatment response;Ulcer;Ulcerative Colitis;Wild Type Mouse;WNT Signaling Pathway;Work;wound;wound healing

PROJECT_TITLE: Roles for Adenomatous polyposis coli in colon injury prevention and wound healing

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Congenital Heart Disease;Genetics;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric;Rare Diseases

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE The goal of this project is to demonstrate the functional and biochemical consequences of a large number of variants of uncertain significance in the gene (KCNQ1) responsible for most cases of the congenital long-QT syndrome (LQTS), a genetic disorder of heart rhythm that carries an elevated risk of sudden death. Results from this study will be used to develop an artificial intelligence method to predict KCNQ1 dysfunction. Our work will enhance the value of genetic testing for LQTS and enable more informed medical decisions regarding this disease.

PI_NAMEs: GEORGE, ALFRED L. (contact);SANDERS, CHARLES R

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Address;Algorithms;Arrhythmia;artificial intelligence method;artificial neural network;Benign;Biochemical;Biological Assay;biophysical techniques;Cell membrane;Cell surface;Classification;ClinVar;Conserved Sequence;Custom;Data;data integration;Data Set;Databases;Decision Making;deep neural network;Disease;Electrophysiology (science);experimental study;Flow Cytometry;Foundations;Free Energy;Functional disorder;Funding;Genes;Genetic Diseases;genetic testing;genetic variant;Goals;heart rhythm;Impairment;improved;interdisciplinary approach;Intervention;Knowledge;Long QT Syndrome;loss of function;Machine Learning;machine learning algorithm;Medical;Medical Genetics;Methods;model building;molecular dynamics;multidisciplinary;mutation screening;nano;neural network;Neural Network Simulation;novel;Online Systems;Output;patch clamp;Pathogenicity;Patient Care;Performance;Population;prediction algorithm;predictive modeling;Productivity;Property;protein transport;Proteins;Research;Risk;Risk Factors;Scanning;sensor;Single Nucleotide Polymorphism;standard of care;Structure;Sudden Death;Test Result;Testing;tool;trafficking;Training;training data;Variant;variant of unknown significance;voltage;Work

PROJECT_TITLE: Decrypting Variants of Uncertain Significance in Long-QT Syndrome


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Infectious Diseases;Prevention;Primary Health Care;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: TEMPE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: Project Narrative We will rigorously evaluate existing immune and viral biomarkers in blood and saliva to develop clinical screening paradigms for the early detection of HPV-associated head and neck cancers.

PI_NAMEs: ANDERSON, KAREN SUE (contact);STURGIS, ERICH MADISON

PROGRAM_OFFICER_NAME: WANG, WENDY

PROJECT_TERMS: Academic Medical Centers;Address;advanced disease;Age;aggressive therapy;anti-cancer research;Antibodies;Area;Arizona;assay development;Back;Binding;biobank;Biological Assay;Biological Markers;biomarker development;biomarker performance;biomarker validation;Blinded;Blood;blood-based biomarker;cancer biomarkers;Cancer Control;Cancer Etiology;Cancer Patient;cancer prevention;cancer recurrence;carcinogenesis;Caring;Cervical Cancer Screening;circulating biomarkers;Clinical;clinical application;Clinical Management;Clinical Research;cohort;Collaborations;Collection;comparative;Controlled Clinical Trials;COVID-19;COVID-19 assay;COVID-19 vaccine;Data;design;Detection;Development;Diagnosis;Diagnostic;digital;DNA;Dryness;Early Detection Research Network;Early Diagnosis;Enrollment;Enzyme-Linked Immunosorbent Assay;experience;Feasibility Studies;feasibility testing;Fingers;Foundations;Funding;Gender;General Population;Geographic Locations;Goals;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;High Risk Woman;Home;HPV oropharyngeal cancer;HPV positive;HPV screening;Human;Human Papilloma Virus Vaccination;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Human papillomavirus 16;Immune;immunogenicity;Immunoglobulin G;improved;Incidence;Individual;Infection;Infrastructure;innovation;instrument;Laboratories;Malignant neoplasm of cervix uteri;malignant oropharynx neoplasm;men;Methodology;Methods;migration;Morbidity - disease rate;mortality;Newly Diagnosed;novel;Nucleic Acid Amplification Tests;Nucleic Acids;Oncoproteins;operation;Oral health;oral HPV-positive head and neck cancers;Oropharyngeal;Participant;patient population;Patients;Peer Review Grants;Performance;peripheral blood;Phase;Phase III Clinical Trials;Plasma;Population;Predictive Value;Prevalence;programs;prospective;Prospective Studies;public health priorities;Publications;Reagent;repository;Research;research clinical testing;Research Design;Research Institute;Resources;response;Risk;Risk Assessment;risk prediction;Saliva;saliva diagnostic;saliva sample;Salivary;salivary assay;sample collection;Sampling;School Dentistry;screening;Screening for cancer;screening program;serological marker;Serology;Serology test;Serum;Specimen;Speed;Spottings;success;System;Technology;Testing;Texas;underserved community;Universities;Validation;validation studies;Viral

PROJECT_TITLE: Southwest EDRN Clinical Validation Center for Head and Neck Cancer


NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Biomedical Imaging;Clinical Research;Neurosciences;Rehabilitation

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: Project Narrative This grant proposal is motivated by the need to improve the safety and efficiency of imaging patients with neural implants with MR scanners. 3T MR systems can produce high-resolution images, however, the specific absorption rate (SAR) or the power deposited in patients with metallic implants may cause unsafe tissue heating. The goal of this research, is to extend the use of MRI to patients with conductive implants, who currently cannot be scanned.

PI_NAMEs: ERYAMAN, YIGITCAN  (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: absorption;Acceleration;Acute;Affect;Age;Anesthesia procedures;Animals;Applications Grants;base;Bilateral;brain tissue;Cadaver;Clinical;Complex;Data;Deep Brain Stimulation;Deposition;Devices;Disease;Electrodes;Electromagnetic Fields;Electromagnetics;Ensure;experimental study;Family suidae;Freedom;Friends;Future;General Population;Goals;Head;Heating;high resolution imaging;Histology;Human;human subject;Image;imaging modality;Imaging technology;Implant;implant design;implantable device;implantation;Implanted Electrodes;improved;Institutional Review Boards;Location;Magnetic Resonance Imaging;Measures;Medical Device;medical implant;Medicine;metallicity;Methods;models and simulation;Monitor;Morphologic artifacts;MRI Scans;neural implant;Neuromodulator;Patient imaging;Patients;Pattern;Performance;performance tests;Phase;Physiologic pulse;Public Health;radio frequency;Research;Resistance;Safety;Scanning;Scheme;Secure;simulation;Slice;System;Temperature;Time;Tissues;transmission process;voltage;Work

PROJECT_TITLE: Safe Magnetic Resonance Imaging of Patients with Deep Brain Stimulation Systems

STUDY_SECTION: EITN

STUDY_SECTION_NAME: Emerging Imaging Technologies in Neuroscience Study Section[EITN]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: SEATTLE

ORG_NAME: ALLEN INSTITUTE

ORG_STATE: WA

PHR: Project Narrative Our goal is to gain a deeper mechanistic understanding of how external electric brain stimulation impacts the brain at the single-neuron and cell type-specific level. Using a number of techniques such in vitro multipatch electrophysiology and high-density Neuropixels in vivo recordings, this work will enable the design of novel stimulation protocols offering improved selectivity, specificity and efficacy of ES application in rodent and, uniquely, human single-neurons and cell types. Taken together, this effort will develop new and improved ES technologies with potential applications in treatment of neurological disorders such as epilepsy, dementia, and Parkinson’s disease.

PI_NAMEs: LEE, SOO YEUN  (contact)

PROGRAM_OFFICER_NAME: HWANG, GRACE MEI-HUA

PROJECT_TERMS: Action Potentials;Affect;Area;awake;Biophysical Process;Brain;brain tissue;cell type;Cells;Classification;Collaborations;Coupling;Data;Dementia;density;design;Distant;Electric Stimulation;Electrical Stimulation of the Brain;Electrodes;Electrophysiology (science);Epilepsy;Exhibits;extracellular;Frequencies;Gene Expression Profile;Goals;Head;Hippocampus;Hospitals;Human;improved;In Vitro;in vitro activity;in vivo;insight;Intervention;Investigation;Knowledge;Location;Maps;Measures;Medial;medial temporal lobe;Monitor;Morphology;multimodal data;multimodality;Mus;Neocortex;Nervous System Disorder;neural circuit;neuronal circuitry;Neurons;novel;Outcome;Parkinson Disease;patch clamp;Pathologic;Pattern;Phase;Physiological;preference;Property;Protocols documentation;Research;response;Rodent;single-cell RNA sequencing;Site;Slice;spatiotemporal;Specificity;Stimulus;System;Techniques;Technology;Testing;Therapeutic;Therapeutic Intervention;tool;Transgenic Organisms;Work

PROJECT_TITLE: Multi-modal, large-scale characterization of cellular and cell-type-specific effects with electric stimulation in rodent and human brain


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Autoimmune Disease;Brain Disorders;Clinical Research;Microbiome;Multiple Sclerosis;Neurodegenerative;Neurosciences;Nutrition;Substance Misuse

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Project Narrative The underlying cause of multiple sclerosis (MS) remains elusive and is likely due to a combination of genetics and environmental exposures, with the growing appreciation that environmental factors, such as diet and the gut microbiome contribute to a large degree of the MS susceptibility risk. Alcohol is a common dietary factor used by MS patients and yet, despite its widespread use, potential for abuse and known gut, CNS and immune effects, alcohol’s role in MS is not well understood. The proposed research will begin to define alcohol’s dose-dependent effects in neuroinflammation by examining the immune system and the gut microbiome with the vision of generating hypotheses that can inform the direction and design of future diet studies in EAE and MS and expand the repertoire of available targeted MS probiotics.

PI_NAMEs: MELAMED, ESTHER  (contact)

PROGRAM_OFFICER_NAME: WANG, JOE

PROJECT_TERMS: Ablation;abuse liability;Address;Adoptive Transfer;Affect;Alcohol consumption;Alcohol dependence;alcohol effect;alcohol research;Alcohols;Animals;Anti-Inflammatory Agents;Antiinflammatory Effect;Astrocytes;Autoimmune Diseases;Automobile Driving;Basic Science;binge drinking;Bioinformatics;Biology;Blood - brain barrier anatomy;career development;Caring;Cells;Central Nervous System;Chronic;Clinical;Clinical Investigator Award;clinical training;CNS Demyelinating Autoimmune Diseases;Communication;Consumption;Critical Pathways;Data;density;design;Development;Diet;dietary;Dietary Factors;Disabling;Disease;Disease Outcome;disorder risk;Dose;Environmental Exposure;Environmental Risk Factor;enzyme linked immunospot assay;epidemiology study;Etiology;evidence base;experience;Experimental Autoimmune Encephalomyelitis;experimental study;Firmicutes;Flow Cytometry;Foundations;Funding;Future;Genes;Genetic;Germ-Free;gut microbiome;gut microbiota;gut-brain axis;Immune;Immune response;Immune system;Immunohistochemistry;Immunology;Individual;Inflammatory;insight;Investigation;Lead;Link;male;Mediating;medical schools;Mentors;Mentorship;microbial;microbiome;microbiome research;microbiota;Microglia;Modeling;mouse model;Multiple Sclerosis;multiple sclerosis patient;Mus;Nerve Degeneration;Neurobiology;Neuroimmune;neuroimmunology;neuroinflammation;Neurological disability;Neurology;neuroprotection;Outcome;Patients;Pattern;Peripheral;Peripheral Nervous System;Persons;Phenotype;Physicians;Predisposition;Probiotics;professor;Program Development;Regulatory T-Lymphocyte;Research;Risk;Role;Scientist;sex;Sex Differences;sexual dimorphism;Spinal Cord;Symptoms;System;T cell therapy;T-Lymphocyte;Testing;Therapeutic;Training;transcriptome sequencing;transcriptomics;treatment response;Vision;Vocational Guidance;Work;young adult

PROJECT_TITLE: Alcohol's Impact on the Gut-Brain Axis in a Mouse Model of Multiple Sclerosis

STUDY_SECTION: AA

STUDY_SECTION_NAME: Neuroscience and Behavior Study Section[AA-4]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Infectious Diseases;Mental Health;Pediatric;Prevention;Social Determinants of Health;Substance Misuse;Telehealth

ORG_CITY: SAN FRANCISCO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Narrative: Addressing mental health and substance use challenges in the context of other barriers to care among youth and young adults living with HIV is more critical than ever to improve engagement in HIV care and end the HIV epidemic. Using a differentiated model of care approach, we will test the efficacy of an intervention including video-counseling along with a mobile health application on HIV virologic suppression among 18–29-year-olds living with HIV.

PI_NAMEs: SABERI, PARYA  (contact)

PROGRAM_OFFICER_NAME: KAMATH, SUSANNAH M A

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adult;Age;age group;AIDS prevention;Algorithms;antiretroviral therapy;arm;barrier to care;Behavioral;Caring;Characteristics;Clinical;Collaborations;Communities;community partnership;Continuity of Patient Care;Counseling;Data;design;Diagnosis;disability;Economics;efficacy testing;Epidemic;Event;Evidence based intervention;experience;Face;Failure;forgetting;Foundations;Friends;Geography;Goals;Health;health care availability;health disparity;Health Personnel;Health Professional;Healthcare;HIV;Home;human centered design;human old age (65+);Human Resources;improved;Individual;innovation;Intervention;Life Expectancy;Logistics;Medication Management;Mental disorders;Mental Health;Methods;Mobile Health Application;Modeling;Morbidity - disease rate;mortality;Motivation;Outcome;Participant;primary outcome;Professional counselor;Provider;Quality of life;Randomized;randomized, clinical trials;Research;Resources;responders and non-responders;Risk;Service provision;Services;skills;Social isolation;social stigma;Social Workers;socioeconomics;standard of care;Substance Addiction;substance use;substance use treatment;technology intervention;Testing;Theoretical model;therapy adherence;Time;Training;transmission process;treatment arm;Treatment Efficacy;treatment services;treatment strategy;video chat;video coaching;Viral;young adult;Youth

PROJECT_TITLE: Comprehensive, tailored, technology-based intervention to improve virologic suppression among youth and young adults living with HIV

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-RPHB-M(53)]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Climate-Related Exposures and Conditions

ORG_CITY: Chicago

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: PROJECT NARRATIVE  Methane is a potent greenhouse gas that drives climate change and represents an appreciable burden on human and environmental health. A promising route toward mitigating climate change exists in the particulate methane monooxygenase (pMMO), a copper-dependent transmembrane enzyme from methanotrophic bacteria that oxidizes methane to methanol, a desirable biofuel. This project involves the use of innovative membrane mimetics to render pMMO more amenable for study, addressing longstanding questions about this important enzyme and membrane proteins in general, which are underrepresented in structural studies and fundamentally important in human health.

PI_NAMEs: TUCCI, FRANK  (contact)

PROGRAM_OFFICER_NAME: RAVICHANDRAN, LINGAMANAIDU V

PROJECT_TERMS: Active Sites;Address;Affect;anthropogenesis;Atmosphere;atmospheric carbon dioxide;Bacteria;Bathing;Biochemical;Biological;Biophysics;Catalogs;chemical reaction;Chemistry;climate change;climate instability;Consumption;Copper;Cryoelectron Microscopy;Data;design;Detergents;Electron Transport;Environment;Environmental Health;Enzymes;Equation;Exhibits;Failure;Future;future pandemic;Goals;greenhouse gases;Health;Homeostasis;Human;Human Activities;Hydrophobicity;innovation;insight;Interdisciplinary Study;interest;Knowledge;Lipid Bilayers;lipidomics;Lipids;Liquid substance;Mass Spectrum Analysis;Membrane;Membrane Proteins;Metals;Methane;Methane hydroxylase;Methane Metabolism Pathway;Methanol;Methylococcaceae;Methylococcus capsulatus;Micelles;Microbe;mimetics;Modeling;Molecular Structure;nanodisk;Natural Gas;Outcome;oxidation;Oxidoreductase;partial recovery;Particulate;Pathway interactions;Physiological;Play;preservation;pressure;Process;Property;protein protein interaction;protein structure;Proteins;reconstitution;Recovery;Reducing Agents;Research;Resolution;Risk;Role;Route;Scaffolding Protein;Scientist;Structure;System;Temperature;Testing;Training Programs;Transmembrane Domain;tropospheric ozone;Visualization

PROJECT_TITLE: Investigating the role of the membrane in particulate methane monooxygenase (pMMO) structure and function


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Opioid Misuse and Addiction;Opioids;Racial and Ethnic Minority Health Research;Recovery Support Services;Social Determinants of Health;Substance Misuse

ORG_CITY: COLLEGE PARK

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: Project Narrative Low-income, racial/ethnic minority individuals with opioid use disorder (OUD) face the greatest disparities in OUD treatment outcomes, including experiencing significant barriers to MAT retention. Implementing a reinforcement-based, behavioral activation intervention delivered to support retention in MAT using peer recovery coaches may be a feasible, acceptable, and sustainable way to improve MAT outcomes among underserved, minority individuals with OUD.

PI_NAMEs: MAGIDSON, JESSICA F (contact)

PROGRAM_OFFICER_NAME: MARTIN, LINDSEY ANN

PROJECT_TERMS: Abstinence;addiction;Address;Adherence;Adoption;Affect;African American population;Agreement;Baltimore;Behavior;Behavior Therapy;Behavioral;Caring;Cities;Client;Clinic;combat;community setting;contingency management;cost;cost effective;Counseling;depressive symptoms;design;Disparity;effectiveness evaluation;effectiveness/implementation study;effectiveness/implementation trial;efficacious treatment;Enrollment;Epidemic;ethnic minority;ethnic minority population;evidence base;Evidence based intervention;experience;Face;Fatality rate;Feedback;flexibility;Focus Groups;Future;Health Services Accessibility;HIV;housing instability;Hybrids;implementation barriers;implementation facilitators;implementation outcomes;improved;improved outcome;Individual;innovation;Intervention;Lived experience;Location;Low income;Manuals;medically underserved;Medically Underserved Area;medication compliance;medication-assisted treatment;Mental Depression;Methods;Minority;Minority Groups;Modeling;mortality;multidisciplinary;open label;Opioid;opioid treatment program;opioid use disorder;Outcome;Outpatients;overdose death;Patient Self-Report;Patients;peer;peer recovery;Phase;phase 2 study;Positive Reinforcements;prevent;Procedures;Proctor framework;Professional counselor;Provider;provider-level barriers;Psychological reinforcement;psychosocial;Psychosocial Factor;Quality of life;racial minority;Randomized;Relapse;Research;Services;social stigma;structural determinants;Substance Use Disorder;Testing;Toxicology;Training;treatment adherence;treatment as usual;Treatment outcome;treatment program;underserved community;Underserved Population;Urine;Work

PROJECT_TITLE: Peer-Delivered Behavioral Activation Intervention to Improve Adherence to MAT Among Low-Income, Minority Individuals With OUD

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cocaine;Drug Abuse (NIDA only);Opioid Misuse and Addiction;Opioids;Social Determinants of Health;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: Washington

ORG_DEPT: PSYCHOLOGY

ORG_NAME: AMERICAN UNIVERSITY

PHR: The proposed research will provide fundamental new knowledge that will increase our understanding of substance use disorders. This will be accomplished by using an animal model to investigate the factors that cause individuals to choose heroin or cocaine over non-drug alternatives. The information gained from this research can be used to improve treatments for substance use disorders, a major public health problem today.

PI_NAMEs: KEARNS, DAVID N (contact)

PROGRAM_OFFICER_NAME: MOORE, HOLLY MARIE

PROJECT_TERMS: addiction;Affect;Animal Model;Animals;Behavior;behavioral economics;Cocaine;Complement;Consumption;Cues;Data;Drug abuse;Drug Interactions;Drug Modelings;drug seeking behavior;drug testing;Drug usage;Drug user;Economics;Essential Drugs;experience;Goals;Heroin;Human;improved;Individual;Individual Differences;insight;Intoxication;Kava;Knowledge;Laboratory Finding;Learning;Measures;Methods;Mission;Modeling;Motivation;National Institute of Drug Abuse;Nature;Negative Reinforcements;Negative Reinforcer;non-drug;Opioid;Pharmaceutical Preparations;Play;Positioning Attribute;Positive Reinforcer;Price;Procedures;Property;psychostimulant;Public Health;Rattus;Recreation;reinforcer;Research;Rewards;Role;Saccharin;Self Administration;Social Interaction;Substance Use Disorder;substance use treatment;Testing

PROJECT_TITLE: Opioid and Psychostimulant Taking: Testing the Impact of Behavioral Economic Contexts

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


NIH_SPENDING_CATS: Clinical Research;Kidney Disease;Precision Medicine

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Public Health Relevance Statement The Kidney Precision Medicine Project was established in 2016 to discover novel therapies for acute kidney injury through the study of human kidney tissue obtained during hospitalization. In this second phase of KPMP, research study recruitment and retention of participants with acute kidney injury will continue at two sites in order to collect kidney tissue while maintaining a high degree of procedural safety. Participant data and samples will be shared with the Kidney Precision Medicine Project consortium and with the wider research community in an ethical manner while protecting participant privacy.

PI_NAMEs: PARIKH, CHIRAG R (contact)

PROGRAM_OFFICER_NAME: GIPSON, DEBBIE SUE

PROJECT_TERMS: Academic Medical Centers;Acute Renal Failure with Renal Papillary Necrosis;Address;Adverse event;adverse outcome;Biological Markers;Biopsy;Blood;Cardiovascular system;Cessation of life;Chronic Kidney Failure;Clinical;Clinical Data;Clinical Research;cohort;Collaborations;Communities;COVID-19 pandemic;Critical Care;Data;Data Linkages;data quality;data sharing;Development;diagnostic tool;DNA;Electronic Health Record;Enrollment;Ensure;Ethics;ethnic diversity;Ethnic Origin;Etiology;Evaluation;Event;experience;Experimental Animal Model;follow-up;Funding;Future;Goals;Health;Heterogeneity;Hospital Mortality;Hospitalization;Human;Hybrids;improved;Incidence;Injury to Kidney;Kidney;kidney biopsy;Kidney Diseases;Leadership;Link;Longitudinal Studies;Measures;Medical;Methods;Molecular;Molecular Target;Monitor;National Institute of Diabetes and Digestive and Kidney Diseases;Nature;new therapeutic target;novel;novel diagnostics;novel therapeutics;outreach;Participant;participant enrollment;participant retention;participant safety;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Patient Outcomes Assessments;Patient Recruitments;Patients;Persons;Pharmaceutical Preparations;Phase;Phenotype;Physicians;Play;Policies;precision medicine;prevent;Primary Care;Privacy;Process;programs;Proteins;Protocols documentation;public health relevance;Race;Radiology Specialty;recruit;remote visit;renal damage;Research;Research Personnel;research study;Role;Safety;Sampling;Severities;sex;Site;success;Therapeutic;tissue resource;Tissues;United States National Institutes of Health;Universities;Urine;Validation;Work

PROJECT_TITLE: AKI Matched Phenotype Linked Evaluation with Tissue (AMPLE-Tissue)


ED_INST_TYPE: HOSPITALS

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: NARRATIVE The proposal seeks to investigate the role of RAS/ERK signaling in sculpting the small non-coding RNA landscape via phosphorylation of Dicer1, Drosha and DIS3 to regulate and coordinate maternal transcriptome and proteome with oocyte-to-embryo transition and embryonic morphogenesis. Because meiosis I and role of RAS signaling is a fundamental and conserved process across metazoans, the knowledge gained from this research has implications to understanding both infertility and birth defects. Additionally, we find that ERK-mediated Dicer1 phosphorylation correlates with aggressive human endometrial cancers and unregulated phosphorylated Dicer1 activity leads to sterility in mouse models, this work will thus also inform mammalian biology.

PI_NAMEs: ARUR, SWATHI  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: Area;Arginine;Biogenesis;Biological Assay;Biology;Birth;Caenorhabditis elegans;Cell Culture System;Cells;Congenital Abnormality;CRISPR/Cas technology;Development;Disease;Embryo;Embryonic Development;Endometrial Carcinoma;Event;exosome;Generations;genome editing;Growth Factor;Human;Human Biology;human female;Image;in vivo Model;Infertility;Investigation;Knowledge;Light;Link;Malignant Neoplasms;Mammalian Cell;Mammals;Mediating;Meiosis;Methods;Methylation;Modeling;Morphogenesis;mouse model;next generation sequencing;oocyte quality;Oocytes;Phosphorylation;Population;Process;Proteome;Proteomics;Puberty;Regulation;Reproduction;Research;RNA;RNA Degradation;Role;Signal Transduction;Small RNA;sperm cell;Sterility;transcriptome;Untranslated RNA;Work

PROJECT_TITLE: ERK-mediated regulation of non-coding RNAs during development and disease

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


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE The proposed research is relevant to NIH because it is a basic science oriented proposal that has strong translational potential. The proposal will identify novel molecular mechanisms regulating normal heart function and their remodeling in heart failure. The identified mechanisms will be able to be targeted for new (and greatly needed) therapeutic development for failing hearts.

PI_NAMEs: HONG, TINGTING ;SHAW, ROBIN M (contact)

PROJECT_TERMS: absorption;Actins;Affect;American;Animals;Basic Science;Biological;biosignature;Calcium;Cardiac;Cardiac health;Cardiac Myocytes;Cardiomyopathies;Cell Line;Cell model;Cells;Connexin 43;Coupling;Cytoskeleton;Data;Development;Disease;Epidemic;extracellular;extracellular vesicles;Functional disorder;gene therapy;Genetic;Goals;Heart;Heart Diseases;Heart failure;heart function;Homeostasis;Human;Impairment;improved;In Vitro;in vivo;innovation;Intercalated disc;L-Type Calcium Channels;Laboratories;Maintenance;Membrane;Membrane Biology;Methods;Microtubules;Modeling;Molecular;mouse model;Movement;Mus;Muscle Cells;Myocardium;novel;novel diagnostics;novel marker;novel therapeutic intervention;novel therapeutics;Outcome;Pathologic;Pathway interactions;pharmacologic;preservation;Publishing;Recycling;Regulation;Relaxation;Reporting;Research;Resources;restoration;Ryanodine Receptor Calcium Release Channel;Source;Stress;Surface;Syndrome;targeted delivery;targeted treatment;Testing;Therapeutic;therapeutic development;therapy development;tool;trafficking;translational impact;translational potential;United States;United States National Institutes of Health;Ventricular;Vesicle;vesicular release

PROJECT_TITLE: Regulation of Cav1.2 Trafficking by GJA1-20k and cBIN1

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Neurosciences;Regenerative Medicine;Transplantation

ORG_CITY: IRVINE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE/RELEVANCE Dysfunction of GABAergic inhibitory circuits has been implicated in many neurodevelopmental and neuropsychiatric disorders, such as amblyopia, epilepsy, and schizophrenia. This proposal aims to determine the role of Calbindin, an understudied plasticizing molecule, in reactivating developmental plasticity in adult inhibitory neurons. By elucidating the cell and molecular mechanisms underlying this rejuvenation, our work may open novel therapeutic avenues for brain repair.

PI_NAMEs: NAKAYAMA, TAYLOR  (contact)

PROGRAM_OFFICER_NAME: CLAYTON, EDWIN C

PROJECT_TERMS: Adolescent;Adult;Age;Amblyopia;Binding Sites;Bioinformatics;Biological;brain repair;calbindin;Calcium-Binding Proteins;Cell Transplantation;Cells;cellular development;Cementation;Clinical;Communication;critical developmental period;critical period;Data;Development;developmental plasticity;differential expression;Educational process of instructing;England;Epilepsy;experience;Functional disorder;Functional Imaging;Gene Expression Profile;Genes;Genetic Transcription;genome-wide;Goals;graduate student;Immunohistochemistry;inhibitory neuron;Injections;insight;LoxP-flanked allele;Memory impairment;Molecular;monocular deprivation;Mus;nerve stem cell;Nervous System Disorder;neural circuit;Neurodevelopmental Disorder;Neurons;neuropsychiatric disorder;novel;novel therapeutics;Ocular Dominance;Ontology;optical imaging;outreach;overexpression;Parabiosis;Pathway Analysis;Pathway interactions;permissiveness;Population;Postdoctoral Fellow;Process;progenitor;protein protein interaction;Rejuvenation;repair strategy;repaired;Resources;Role;Schizophrenia;sensory input;Signal Pathway;Signal Transduction;skills;Statistical Data Interpretation;stem;Structure;Synaptic plasticity;Testing;Therapeutic;therapeutic development;Time;Training;Transcript;transcription factor;transcriptome sequencing;transcriptomics;Transplant Recipients;Transplantation;Up-Regulation;Viral;Vision;Visual;Visual Cortex;Work

PROJECT_TITLE: The role of Calbindin in developmental and transplant-reactivated cortical plasticity


NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Cancer cells must activate a telomere lengthening mechanism to ensure proliferation and survival. 15% of cancer cells utilize a telomerase-independent pathway termed the Alternative Lengthening of Telomeres (ALT). The deregulation of ADP-ribosylation, a post-translational modification that regulates several cellular processes including transcription, metabolism, and DNA repair, inhibits ALT cancer cell survival. Despite the high importance of ADP-ribosylation as a modification found on proteins, recent groundbreaking studies have established nucleic acids as bona fide substrates of ADP-ribosylation in mammalian cells and this paradigm shift has significant implications for our understanding of the true physiological function of ADP-ribosylation. I identified that telomeres are endogenous cellular targets of DNA ADP-ribosylation and therefore, I seek to characterize the impact on the ALT pathway, as well as the consequences that its perturbation has on cellular physiology and cancer cell survival.

PI_NAMEs: WONDISFORD, ANNE  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: Adenosine Diphosphate Ribose;ADP ribosylation;ATRX gene;Biological Assay;cancer cell;Cancer cell line;Cancer Patient;cancer therapy;Cell Death;Cell Death Induction;Cell Physiology;Cell Survival;Cells;cellular targeting;Chromatin;chromatin remodeling;Chromatin Remodeling Factor;Chromosomes;Clinical;Complement;Complex;Data;DAXX gene;Defect;Deposition;Development;DNA;DNA Damage;DNA Modification Process;DNA Repair;DNA Sequence;Ensure;Enzyme Inhibition;Enzymes;Excision;Exposure to;Functional disorder;Genes;Genetic Transcription;Glycoside Hydrolases;Histones;homologous recombination;homologous recombination deficiency;Hydrolase;Hydrolysis;Impairment;improved;In Vitro;innovation;insight;Investigation;Knowledge;Laboratories;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant neoplasm of prostate;Malignant Neoplasms;Mammalian Cell;Mediating;Mediator;Metabolism;Modification;Monitor;mutant;Mutate;Mutation;novel;Nucleic Acids;Outcome;Pathway interactions;pharmacologic;Physiological;Poly Adenosine Diphosphate Ribose;poly ADP-ribose glycohydrolase;Poly(ADP-ribose) Polymerase Inhibitor;Poly(ADP-ribose) Polymerases;Post-Translational Protein Processing;Proliferating;Proteins;recruit;Recurrence;repaired;Research;RNA;RNA-Directed DNA Polymerase;Role;sensor;Source;Stress;Structure;targeted treatment;Telomerase;telomere;Telomere Length Maintenance;Telomere Pathway;TERF1 gene;therapy development;tool

PROJECT_TITLE: Understanding the impact of DNA ADP-ribosylation on telomere function in cancer cells


NIH_SPENDING_CATS: Aging;Autoimmune Disease;Brain Disorders;Immunotherapy;Neurodegenerative;Neurosciences;Parkinson's Disease

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE a-Synuclein accumulates in the brains of Parkinson’s disease patients, and often coincides with immune cell infiltration from circulation into the brain. The proposed study will investigate whether autoreactive T cells targeting a-synuclein infiltrate the brain and contribute to neuroinflammation and neurodegeneration. This study has the potential to implicate autoimmunity as a driver of Parkinson’s disease pathogenesis, and point to potential immunomodulatory therapies for treatment of the disease.

PI_NAMEs: MONAHAN, CONNOR  (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, LUIS FLANAGAN

PROJECT_TERMS: adaptive immune response;Adoptive Transfer;Affect;Affinity;Alleles;alpha synuclein;Autoimmune Responses;Autoimmunity;autoreactive T cell;autoreactivity;Binding;Brain;CD4 Positive T Lymphocytes;Cell Physiology;Cells;Central Nervous System;Chronic;Circulation;Clinical;cohort;combinatorial;Complex;Constipation;Data;density;Development;Disease;disease diagnosis;Disease Progression;dopamine transporter;dopaminergic neuron;Encephalomyelitis;Enteral;Experimental Autoimmune Encephalomyelitis;Flow Cytometry;Generations;genome wide association study;Homing;Human;humanized mouse;ileum;Immune;immune activation;immune cell infiltrate;Immune response;Immune system;Immunization;Immunize;Immunohistochemistry;immunomodulatory therapies;Infiltration;Inflammation;Intestines;Knowledge;Lewy Bodies;Lewy body pathology;Lewy neurites;Link;Mediating;Methods;MHC Class II Genes;Microglia;Midbrain structure;Modeling;motor deficit;mouse model;Multiple Sclerosis;Mus;Nerve Degeneration;Neurodegenerative Disorders;neurodegenerative phenotype;neuroinflammation;neuron loss;Neurons;novel;overexpression;Parkinson Disease;Pathogenesis;Pathologic;Pathology;Patients;Peptides;Peripheral;Phenotype;Play;Process;Proteins;Publishing;receptor;Reporting;risk variant;Role;single-cell RNA sequencing;Stimulus;Substantia nigra structure;synuclein;T cell infiltration;T cell response;T cell therapy;T-Cell Activation;T-Lymphocyte;Testing;Time;Transgenic Mice;Transgenic Organisms;Tyrosine 3-Monooxygenase;Viral

PROJECT_TITLE: Alpha-Synuclein-Specific T cells in Parkinson's Disease Pathogenesis