NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Child Abuse and Neglect Research;Clinical Research;Mental Health;Nutrition;Obesity;Pediatric;Physical Activity;Prevention;Social Determinants of Health;Violence Research

ORG_CITY: PROVIDENCE

ORG_NAME: BUTLER HOSPITAL (PROVIDENCE, RI)

ORG_STATE: RI

PHR: Project Narrative: Converging lines of evidence indicate that stress, and childhood adversity in particular, accelerates the aging process, leading to impairment, suffering, and disease. The proposed study examines the role of mitochondria in this process, leveraging data available in an existing study of childhood adversity that includes rich data on exposures, health behaviors, and health outcomes. Results of this study are expected to provide insight into the biological mechanisms of risk for accelerated aging and risk for disease, and provide targets for new treatment and prevention approaches.

PI_NAMEs: TYRKA, AUDREY  (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: Acceleration;Acute;Adult;Age;age acceleration;age related decline;age-related disease;aging biomarker;aging process;aging related;Animal Model;Animals;Anxiety Disorders;anxiety symptoms;Atherosclerosis;Attention;Behavior;Behavioral;Biological;biological adaptation to stress;Cardiovascular Diseases;Cell Aging;Cell Death;Child Abuse and Neglect;Childhood;childhood adversity;Complex;Data;Depressive disorder;depressive symptoms;Diabetes Mellitus;Diet;Disease;disorder risk;DNA copy number;early experience;early life adversity;Early-life trauma;Enzymes;Epigenetic Process;Exercise;Fasting;follow-up;Glucocorticoids;Health;Health behavior;Health behavior and outcomes;Human;Hydrocortisone;Impairment;indexing;Individual;Inflammation;Inflammatory;insight;Insulin Resistance;Intervention;Interview;Laboratories;Leukocytes;Link;Lipids;Measures;Mental disorders;Metabolic Pathway;metabolic rate;Metabolic syndrome;Mitochondria;Mitochondrial DNA;Molecular;Neurosecretory Systems;novel;Obesity;Outcome;Oxidative Stress;Pain;Pathway interactions;pediatric trauma;Pharmaceutical Preparations;Physical activity;Play;poor health outcome;poor sleep;Premature aging syndrome;Prevention approach;Process;prospective;Proteins;psychiatric symptom;Public Health;Reactive Oxygen Species;Recording of previous events;Respiration;Risk;Risk Factors;Role;Sampling;sedentary lifestyle;Signal Pathway;Signal Transduction;Signs and Symptoms;Sleep;Smoking;Specimen;Specimen Handling;Stress;stressor;Stroke;Symptoms;Syndrome;Testing;Time;Trauma;trauma exposure;Unhealthy Diet;vaping;Weight;Work

PROJECT_TITLE: Mechanisms of Accelerated Aging: Stress, Health Behaviors, and the Role of Mitochondria

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Diabetes;Genetics

ORG_CITY: NEW YORK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative Type 2 diabetes can be caused by failure to maintain β-cell identity, resulting in dedifferentiation into endocrine progenitor-like cells. In this regard, whether β-cell dedifferentiation is reversible is one of the most important questions in terms of disease modification. This project will examine the reversibility of β-cell dedifferentiation and the potential therapeutic benefits of genetic and pharmacological inhibition of ALDH1A3 on the reversibility of β-cell failure and its potential as a type 2 diabetes treatment.

PI_NAMEs: SON, JINSOOK  (contact)

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Ablation;Address;aldehyde dehydrogenase 1;Animal Model;Apoptosis;B-Lymphocytes;Back;Beta Cell;blood glucose regulation;Cell Count;cell dedifferentiation;Cell Physiology;Cell Separation;Cells;Cessation of life;Characteristics;Chemicals;Complement;db/db mouse;Diabetes Mellitus;diabetic;Diabetic mouse;Disease;Endocrine;Failure;feeding;Functional disorder;functional restoration;Gene Expression Profile;Generations;Genetic;genetic approach;Genetic Transcription;glucose tolerance;Human;Impairment;improved;In Vitro;in vivo;inhibitor;Insulin;insulin secretion;islet;Knock-in;Knock-out;knockout animal;Knockout Mice;Knowledge;Link;metabolic phenotype;Modeling;Modification;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutic intervention;NR2F6 gene;pharmacologic;Phenotype;Play;Process;Protein Isoforms;Regulation;Role;RXRA gene;stem;stem-like cell;Structure of beta Cell of islet;success;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Work

PROJECT_TITLE: Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of beta cell failure

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


ADMINISTERING_IC: AG

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Complementary and Integrative Health;Genetics

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Post-translational modifications are a well established mechanism of metabolic control. Loss of control is associated with wide-ranging disease states, including the aging process itself. While alterations in protein modifications have been associated with dysregulated metabolism especially in the context of aging, how modifications control metabolism is not known. This key gap in knowledge prevents the generation of effective therapeutics and treatment strategies. Thus, the work described in this proposal is highly relevant to public health because it will determine new mechanisms of action connecting metabolism and nutrient sensing in health and disease.

PI_NAMEs: HIRSCHEY, MATTHEW D (contact)

PROJECT_TERMS: Ablation;Acetyl Coenzyme A;Acetylation;Acetylcysteine;Acetyltransferase;Acyl Coenzyme A;Adipose tissue;Affect;Age;age acceleration;Aging;aging process;Amides;Applications Grants;Automobile Driving;Biochemical;Biological;Biological Assay;Biological Process;Biology;Blood;Brain;Brown Fat;Cell Physiology;Cells;Chemicals;Chemistry;Chromatin;Cysteine;Data;Detection;detection of nutrient;Development;Disease;Dithiothreitol;Drug or chemical Tissue Distribution;Elements;Excision;experimental study;Fasting;feeding;Gender;Gene Expression;Generations;Glutathione Reductase;Goals;Harvest;Health;Heart;Histones;Homeostasis;In Vitro;innovation;Knowledge;Liver;Lysine;Mass Spectrum Analysis;Measures;Mediator;Metabolic;Metabolic Control;Metabolism;Methods;Mitochondria;Modeling;Modification;Mus;novel;Nutrient;nutrient metabolism;Oxidation-Reduction;Peptides;Pharmaceutical Preparations;Phenotype;Physiological;Play;Post-Translational Protein Processing;Posttranslational Amino Acid Modification;Preparation;preservation;Prevalence;prevent;Process;Proline Dehydrogenase;Protein Acetylation;protein function;Proteins;Proteome;Proteomics;Public Health;Reaction;Regulation;response;Role;Running;Sampling;sensor;Series;Side;Signal Transduction;Site;Skeletal Muscle;Skin;Source;Surveys;therapeutically effective;thioester;Tissues;treatment strategy;tris(2-carboxyethyl)phosphine;Wild Type Mouse;Work

PROJECT_TITLE: Studies on the impact of acetyl-cysteine on metabolism

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: DALLAS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative Drugging the oncogenic Wnt/β-catenin pathway is a prominent yet unsolved problem. We have previously found targeting tankyrases a viable approach and now present a solution to address the unexpected resistance issue. This study will cover the development of a new therapeutic agent, a thorough investigation of its mode of action, and the validation of its anticancer potential in mice.

PI_NAMEs: CHEN, CHUO  (contact)

PROGRAM_OFFICER_NAME: GREENBERG, WILLIAM A

PROJECT_TERMS: Action Potentials;Address;ADP ribosylation;Affect;anti-cancer;Antineoplastic Agents;beta catenin;cancer cell;Cancer cell line;Catalysis;Cause of Death;Cell Proliferation;Cells;Cessation of life;Chemicals;clinical investigation;Colon;colon cancer cell line;Colorectal Cancer;Complex;Development;Dimerization;DNA Sequence Alteration;drug action;Epithelial Cells;Genetic;Goals;Hand;Homeostasis;Human;Hyperactivity;Imaging Techniques;improved;in vivo;inhibitor;Intercept;interest;Investigation;knock-down;Link;Liquid substance;live cell imaging;Malignant Neoplasms;Mass Spectrum Analysis;Metabolic;Methods;Molecular;Mus;Mutation;Neoplasm Metastasis;new technology;novel therapeutic intervention;novel therapeutics;Oncogenic;Outcome;Pathway interactions;Penetration;Pharmaceutical Preparations;Phase;Phenocopy;Polymerase;Population;potential biomarker;preclinical study;prevent;programs;Property;Protac;protein degradation;Protein Dynamics;Protein Family;Proteins;Proteome;Proteomics;Reporting;Research;Residual state;Resistance;response;scaffold;Series;Signal Pathway;Signal Transduction;Site;small molecule;Specificity;Tankyrase;Therapeutic;Therapeutic Agents;therapeutic target;Time;tool;Toxic effect;tumorigenesis;Validation;WNT Signaling Pathway;Work;Writing

PROJECT_TITLE: Therapeutic targeting of Wnt signaling in cancer

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: RICHMOND

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Narrative There is no cure for HIV infection due to the viral dormancy in the infected CD4 T cells. This proposed research is relevant to public health and aims to snip out HIV provirus and knock out viral entry coreceptor CCR5 in HIV latently infected T cells by developing a novel CD4-targeted in vivo lentivirus-like particle delivery of CRISPR/Cas ribonucleoprotein and mRNA. Thus, the strategy to excise provirus and prevent virus entry in this proposal is relevant to the part of NIH's mission that helps develop novel therapeutics for the permanent cure of HIV/AIDS.

PI_NAMEs: HU, WENHUI  (contact);LI, QINGSHENG

PROGRAM_OFFICER_NAME: POON, BETTY

PROJECT_TERMS: adeno-associated viral vector;adeno-associated virus 9 delivery;antiretroviral therapy;Binding;Biodistribution;BLT mice;CCR5 gene;CD4 Positive T Lymphocytes;Cell Line;Cells;clinical application;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Data;Disease;DNA;Dose;Engineering;Excision;GAG Gene;gene therapy;Genome;genome editing;genome editor;Glycoproteins;Guide RNA;high reward;HIV;HIV Genome;HIV Infections;HIV-1;HIV/AIDS;Human;humanized mouse;immune activation;Immunity;immunogenicity;improved;In Vitro;in vivo;Infection;innovation;Knock-out;Lentivirus;Mediating;Messenger RNA;Mission;Modeling;Monkeys;mouse model;mRNA delivery;MS2 coat protein;Mus;Nipah;novel;novel therapeutics;particle;Peptides;pharmacokinetics and pharmacodynamics;Phase I Clinical Trials;Positioning Attribute;prevent;Proteins;Proviruses;Public Health;Reporter;Reporting;Research;Resistance;response;Rest;Reverse Transcription;Ribonucleoproteins;RNA;RNA Binding;SIV;Specificity;T-Lymphocyte;Testing;tool;Transcript;Transgenic Mice;United States National Institutes of Health;vector;Vesicle;Viral;Virus;Work

PROJECT_TITLE: Lentivirus-like particle specific delivery of Cas12 ribonucleoprotein (RNP) to HIV reservoir cells in vivo for an HIV cure


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Aphasia;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Frontotemporal Dementia (FTD);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Rare Diseases

ORG_CITY: AUSTIN

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Project Narrative This project’s relevance to public health stems from its efforts to identify aspects of the bilingual experience that are associated with a significantly later age of symptom onset in Hispanics with language-prominent dementia. In addition, this project will address evidence-based treatment approaches for bilingual speakers with progressive language impairments caused by dementia (i.e., primary progressive aphasia). The project will enhance our knowledge of bilingualism as a contributor to cognitive reserve and brain plasticity which will inform theory and clinical practice in this historically underserved population.

PI_NAMEs: GRASSO, STEPHANIE M (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Address;Aftercare;Age;Age of Onset;aging population;Alzheimer's disease related dementia;Aphasia;Attention;Behavior;Behavior assessment;behavior prediction;Behavior Therapy;Behavioral;bilingualism;Brain;Brain region;Characteristics;clinical phenotype;clinical practice;Cognitive;cognitive reserve;cohort;Collaborations;Communication;Confounding Factors (Epidemiology);Dementia;design;Enrollment;Epidemic;Evidence based treatment;experience;Goals;Hispanic;Hispanic Populations;improved;Individual;International;Intervention;Knowledge;Language;Language Development;language impairment;Language Tests;Learning;lexical;lexical retrieval;Life Experience;Linguistics;Literature;Long-Term Effects;Magnetic Resonance Imaging;Maintenance;Measures;Names;Nature;Nerve Degeneration;neural;Neurobiology;neurodegenerative phenotype;neuromechanism;Outcome;Participant;Pattern;Performance;predicting response;Predictive Factor;Primary Progressive Aphasia;Production;Progressive Aphasias;Proxy;Public Health;Rehabilitation therapy;Reporting;Research;resilience;Semantics;Site;social culture;Societies;Spanish;Speech;stem;Symptoms;Syndrome;theories;therapy design;Training;treatment optimization;Treatment outcome;treatment research;treatment response;Underserved Population;Variant

PROJECT_TITLE: Bilingual Factors Associated with Cognitive Reserve and Linguistic Resilience in Hispanics with Primary Progressive Aphasia


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

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Narrative Chronic activation of brain microglial cells and attendant neuroinflammation are major factors in the progression of Alzheimer's disease. We identified novel mechanisms that protect against microglial inflammatory hyperactivation and mitochondrial disfunction, resulting in reduced accumulation of amyloid beta plaques and neuronal cell death. These studies may suggest new therapeutic approaches to treatment of Alzheimer's disease.

PI_NAMEs: ELLISMAN, MARK H;JU, WONKYU ;MILLER, YURY  (contact)

PROGRAM_OFFICER_NAME: DIBATTISTA, AMANDA

PROJECT_TERMS: 3-Dimensional;abeta accumulation;adenovirus mediated delivery;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Amyloid beta-Protein;Apolipoprotein A-I;APP-PS1;Architecture;ATP binding cassette transporter 1;Autopsy;Binding;Binding Proteins;Bioenergetics;Biological Assay;Biopsy;Brain;Cell Death;Cell membrane;Cell Survival;Cells;Characteristics;Cholesterol;Cholesterol Homeostasis;cholesterol transporters;Chronic;Development;Disease associated microglia;Electron Microscopy;extracellular;Face;Flow Cytometry;Genes;Genus Hippocampus;Goals;Hippocampus;Human;human subject;improved;Inflammation;Inflammatory;Inflammatory Response;Knock-out;Knockout Mice;Learning;Light;light microscopy;lipid metabolism;Measures;Mediating;Membrane Microdomains;Memory;Methods;Microglia;Microscopic;Mitochondria;mitochondrial dysfunction;Morphology;mouse model;Mus;Nerve Degeneration;neuroinflammation;neuron loss;novel;novel therapeutic intervention;Oxidative Stress;Pathologic;Phenotype;Physiological;Play;protective effect;Proteins;receptor;recruit;Role;scaffold;Scanning Electron Microscopy;Senile Plaques;Shapes;Signal Transduction;Site;Slice;Study models;tau-1;Testing;Therapeutic;TLR4 gene;tomography;Transgenic Mice;Variant

PROJECT_TITLE: Reversing Microglial Inflammarafts and Mitochondrial Dysfunction in Alzheimer's Disease

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: NOTRE DAME

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF NOTRE DAME

ORG_STATE: IN

PHR: Project Narrative Staphylococcus aureus is an important human bacterial pathogen, which is responsible for significant mortality and morbidity on an annual basis. b-Lactam antibiotics have been preferred for treatment of S. aureus infections over the years, however rampant global resistance to these versatile drugs has resulted in obsolescence of many antibacterial mainstays. We investigate in this grant application the complex machinery that results in b-lactam antibiotic resistance in S. aureus. We also seek novel antibiotics and adjuvant agents that have the ability to reverse the b-lactam-resistance trait, bringing back from obsolescence b-lactam antibiotics for treatment of this problematic bacterium.

PI_NAMEs: MOBASHERY, SHAHRIAR  (contact)

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: Address;Adjuvant;Anti-Bacterial Agents;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Applications Grants;Back;Bacteria;beta-Lactam Resistance;beta-Lactamase;beta-Lactams;Cell membrane;Communication;Complex;Cytoplasm;design;Engineering;Event;Exposure to;Future;Gene Expression;Genes;Growth;Human;inhibitor;Integral Membrane Protein;Kinetics;Lactams;Libraries;Membrane;Membrane Proteins;Methods;Molecular Conformation;Monitor;Monobactams;Morbidity - disease rate;mortality;Natural Products;novel;Operon;pathogenic bacteria;Pathway interactions;Penicillin-Binding Proteins;Pharmaceutical Preparations;Phenotype;Phosphorylation;Phosphorylation Site;Process;Protease Domain;Proteins;Resistance;resistance mechanism;response;screening;sensor;Side;Signal Transduction;small molecule;Staphylococcus aureus;Staphylococcus aureus infection;Structure;Structure-Activity Relationship;Surface;System;tool;tool development;trait;Transducers;United States National Institutes of Health;Work;X-Ray Crystallography

PROJECT_TITLE: Beta-Lactam Resistance Mechanisms of Staphylococcus aureus


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Patient Safety;Radiation Oncology;Women's Health Research

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF VIRGINIA

PHR: Project Narrative While the standard of care for early-stage, estrogen receptor positive breast cancer is breast conserving surgery (BCS) followed by radiation therapy (RT) and 5-10 years of adjuvant endocrine therapy (ET), data from randomized controlled trials support omission of RT in women 65 years and older that take adjuvant ET. However, the majority (70%) of older women still receive RT after BCS, thus raising the concern of over- treatment. Radiation use in this population is multi-factorial, due in part to physician and patient reluctance to omit a treatment in light of concerns that many patients will not complete the recommended course of adjuvant ET due to side effects and thus risk under-treatment. This proposal aims to improve and individualize the treatment of early-stage breast cancer in older women by testing a novel use of a three-month course of pre- operative ET (pre-ET) as a path toward informed decision-making based upon personal experience of ET prior to decisions for adjuvant RT. We plan a clinical trial to evaluate the impact of pre-ET on patient and physician preferences for adjuvant RT and patient-reported decisional conflict and regret.

PI_NAMEs: SHOWALTER, SHAYNA LEFRAK (contact)

PROGRAM_OFFICER_NAME: VIKRAM, BHADRASAIN

PROJECT_TERMS: Address;Adherence;adherence rate;adjuvant endocrine therapy;Adjuvant Radiotherapy;Adjuvant Therapy;Advocacy;Age;Age related comorbidities;Aromatase Inhibitors;Breast;Breast Cancer Patient;Breast-Conserving Surgery;Cancer and Leukemia Group B;Cessation of life;Clinical;Clinical Trials;cohort;comorbidity;Conflict (Psychology);Controlled Clinical Trials;Data;Decision Making;demographics;design;Disease-Free Survival;Distant;DNA Resequencing;Early treatment;Estrogen receptor positive;Estrogen Receptors;experience;Fright;Future;Guidelines;high risk;High Risk Woman;hormone therapy;human old age (65+);improved;Individual;individual patient;individualized medicine;innovation;insight;Intervention;Ipsilateral;Life Expectancy;Light;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Measures;model design;National Comprehensive Cancer Network;Newly Diagnosed;novel;older patient;older women;optimal treatments;Outcome;overtreatment;patient oriented;Patient Outcomes Assessments;Patient Preferences;Patients;Patterns of Care;phase 2 study;Physicians;Population;Prediction of Response to Therapy;preference;Preoperative Endocrine Therapy;preservation;prevent;Prior Therapy;prospective;Provider;Quality of life;Radiation;Radiation therapy;Randomized, Controlled Trials;Recommendation;Recurrent tumor;Regrets;Reporting;response;Risk;Risk Reduction;S-Phase Fraction;side effect;standard of care;Surgical Oncologist;systematic review;Tamoxifen;Testing;therapy adherence;therapy design;Time;tool;treatment center;treatment planning;Treatment Protocols;Treatment-related toxicity;tumor;United States;Update;Woman;women's diagnosis;Women's Group

PROJECT_TITLE: Patient-Centered Insights from the POWER Trial: Pre-Operative Window of Adjuvant Endocrine Therapy to Inform Radiation Therapy Decisions in Older Women with Early-Stage Breast Cancer


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);Biotechnology;Brain Disorders;Cerebrovascular;Dementia;Genetics;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: LEXINGTON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE The strongest genetic risk factor for developing late-onset Alzheimer’s disease is the gene Apolipoprotein E (APOE), where the E4 allele dramatically increases risk while the E2 allele is strongly protective. In this project, we will determine whether ‘allelic switching’ from E4 to E2 will simultaneously rescue multiple neuropathological deficits associated with E4. If successful, this proposal will provide an essential preclinical model for ongoing and future clinical trials, and will provide critical new information regarding opportunities for therapeutic ApoE modulation.

PI_NAMEs: JOHNSON, LANCE ALLEN (contact)

PROJECT_TERMS: Affect;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Amyloid;Amyloid beta-Protein;Amyloid deposition;amyloid pathology;Amyloidosis;Apolipoprotein E;apolipoprotein E-4;Astrocytes;Automobile Driving;Biological;Birth;Brain;brain dysfunction;Candidate Disease Gene;cell type;Cells;cerebrovascular;Cerebrovascular Disorders;Cerebrum;Clinical Trials;Cognitive deficits;Cre lox recombination system;Data;Development;efficacy testing;Functional disorder;Future;Gene Expression Profile;gene therapy;Genes;Genetic;Genetic Recombination;genetic risk factor;Genotype;Homozygote;Human;Hyperlipidemia;Image;Immune;Impaired cognition;in vivo;Individual;induced pluripotent stem cell;Inflammation;interest;Knockout Mice;late life;Late Onset Alzheimer Disease;Length;life span;Link;lipidomics;loss of function;Measures;Metabolic;Metabolism;metabolomics;Modeling;mouse model;Mouse Strains;Mus;Myelin;Nature;Nerve Degeneration;neuroinflammation;Neurons;neuropathology;novel;Odds Ratio;Outcome;overexpression;Pathogenesis;Pathologic;Pathology;Pathway interactions;Peripheral;Phagocytosis;Physiological;Play;Pre-Clinical Model;protective effect;Risk;Role;Series;single-cell RNA sequencing;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;stable isotope;Supplementation;Synapses;tau Proteins;Testing;Therapeutic;transcriptomics

PROJECT_TITLE: APOE Allele Switching as a Therapeutic Approach for Alzheimer's Disease


NIH_SPENDING_CATS: Aging;Cardiovascular;Estrogen;Genetics;Heart Disease;Menopause;Prevention;Women's Health Research

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative Public Health Relevance Statement: The proposed research is relevant to public health because it focuses on unraveling female sex-hormone estrogen-mediated control of epigenetic signaling in young and aged female heart, which plays a critical role in inhibition of cardiac injury. The successful outcome of the proposed studies should define novel mechanism of estrogen regulation and identify potential therapeutic targets for prevention and treatment of cardiac injury in aging female population. Thus, the proposed research is relevant to the National Institute on Aging, part of the NIH's mission to improve the health and well-being of older adults through research.

PI_NAMEs: KUMAR, PRERNA  (contact)

PROGRAM_OFFICER_NAME: GAO, HONGWEI

PROJECT_TERMS: Age;age related;aged;Aging;Binding;Biochemical;Bioinformatics;Blood Pressure;Cardiac;cardiac aging;Cardiac Myocytes;cardioprotection;Cardiovascular Diseases;cardiovascular disorder risk;Cell model;clinical development;Clinical Trials;combinatorial;Data;Dependence;design;digital;disorder risk;Dose;Echocardiography;Environmental Risk Factor;Enzyme-Linked Immunosorbent Assay;Enzymes;Epigenetic Process;Equilibrium;ESR1 gene;Estrogen Receptor 2;Estrogens;expectation;falls;Family;Female;female sex hormone;Future;Gene Expression;Gene Expression Regulation;gene repression;Genes;Genetic;Genetic Transcription;Goals;HDAC2 gene;Health;Heart;heart disease prevention;Heart Diseases;heart function;Heart Hypertrophy;Heart Injuries;Histology;Histone Deacetylase;Hormonal;Hormone replacement therapy;Human;human female;improved;in vivo;innovation;Intervention;Knowledge;male;Measurement;Mediating;menopausal aging;Menopause;Mission;Modeling;Molecular;mRNA Expression;Mus;National Institute on Aging;novel;Nucleic Acid Regulatory Sequences;older adult;Outcome;Ovariectomy;pathological aging;Personal Satisfaction;Pharmaceutical Preparations;Physiological;Play;Population;Post-Menopausal Hormone Replacement Therapy;Postmenopause;Premenopause;prevent;Prevention;promoter;protective effect;Proteins;Public Health;public health relevance;receptor;Regulation;Repression;Research;research and development;response;Response Elements;Risk Factors;Risk Reduction;Role;sex;Signal Transduction;Stress;Techniques;therapeutic target;Tissues;trait;United States National Institutes of Health;Ventricular;Woman

PROJECT_TITLE: Aging and estrogen-dependent HDAC2 regulation: implications in cardiac injury

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TDPS-R(01)]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

ORG_CITY: RESTON

ORG_NAME: AMERICAN ACADEMY OF AUDIOLOGY, INC.

PHR: PROJECT NARRATIVE The American Academy of Audiology’s Academy Research Conferences (ARC) are intended to bridge the gap between clinical practice and academic research by engaging audiologists, scientists, and students in translational presentations and discussions on clinically significant research topics. ARC 2023-2025 exemplifies ARC’s focus on providing access to cutting-edge research for those in clinical practice by addressing significant areas of patient care and management, including future therapeutic options, expanding use of implantable devices, and managing chronic tinnitus.

PI_NAMEs: BOGLE, JAMIE M (contact);JOSEPH, ANTONY

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Academy;Address;American;Applications Grants;Area;Audiology;Auditory;career;Caring;Child Care;Chronic;Clinical;clinical practice;clinically significant;Collaborations;Communities;COVID-19 pandemic;design;Development;Diagnosis;Education;Educational Models;Equilibrium;equity, diversity, and inclusion;Event;Fostering;Funding;Future;graduate student;Hearing;Hearing Aids;hearing impairment;implantable device;improved;Individual;innovation;International;Intervention;Labyrinth;Learning;meetings;Mentors;Mentorship;Methods;multidisciplinary;Nature;next generation;novel therapeutic intervention;Oral;Participant;Patient Care;patient engagement;Patients;Persons;Postdoctoral Fellow;posters;programs;Research;Research Activity;Research Personnel;response;Science;Scientist;Sensorineural Hearing Loss;Series;Students;symposium;Therapeutic;Tinnitus;translational engagement;Translational Research;Underrepresented Populations;United States National Institutes of Health;virtual;Work

PROJECT_TITLE: American Academy of Audiology's Academy Research Conference (ARC) 2023-2025

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Hypertension

ORG_CITY: TOLEDO

ORG_NAME: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS

ORG_STATE: OH

PHR: PROJECT NARRATIVE    Cardiovascular  disease  remains  the  number  one  cause  of  death  in  the  United  States  and  worldwide.  The  proposed  study  utilizes  a  translational  approach  incorporating  the  use  of  transgenic  animal  models,  advanced  smooth muscle cell culture techniques, pharmacological strategies and collaborations with leaders in the field to  rigorously  test  the  hypothesis  that  the  transcription  co- factor  yes- associated  protein  1  induces  smooth  muscle  proliferation and contraction to drive vascular wall thickening and hypertension, respectively. Completion of the  proposed  studies  will  provide  novel  insights  into  the  mechanisms  regulating  vascular  wall  diseases  and  will  determine  if  inhibiting  YAP1  is an  attractive novel therapeutic  strategy  for ameliorating  both occlusive  vascular  diseases and hypertension.

PI_NAMEs: OSMAN, ISLAM  (contact)

PROGRAM_OFFICER_NAME: CATANIA, SELEN MURATOGLU

PROJECT_TERMS: Acetates;Actins;activating transcription factor 1;Angioplasty;Angiotensin II;Animal Model;Arterial Injury;Atherosclerosis;Attenuated;Biological Assay;Blood Pressure;blood pressure reduction;blood pressure regulation;Blood Vessels;Cardiovascular Diseases;career;Cause of Death;Cell Culture Techniques;cofactor;Collaborations;Data;Deoxycorticosterone;Disease;Etiology;Exhibits;gain of function;Genes;Genetic Transcription;genome wide association study;genomic locus;Goals;Hypertension;Hypotensives;Impairment;In Vitro;in vivo;indexing;Infusion procedures;inhibitor;Injury;insight;Knockout Mice;loss of function;Luciferases;Measures;Mediating;mouse model;Mus;Muscle Contraction;neointima formation;novel;novel therapeutic intervention;pharmacologic;Phase;Phenotype;Platelet-Derived Growth Factor;Platelet-Derived Growth Factor beta Receptor;polymerization;Polymers;Prevention;PRKCA gene;Proliferating;Proteins;receptor;Regulatory Pathway;Reporter;Research;Resistance;response;restenosis;Role;Signal Transduction;Single Nucleotide Polymorphism;Smooth Muscle;Smooth Muscle Myocytes;Sodium Chloride;Telemetry;Testing;Training;transcription factor;Transgenic Animals;translational approach;United States;Vascular Diseases;Vascular remodeling;Vascular resistance;Vascular Smooth Muscle;vascular smooth muscle cell proliferation;Vasoconstrictor Agents

PROJECT_TITLE: YAP1, neointima formation, and blood pressure regulation

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


FUNDING_MECHANISM: SBIR-STTR RPGS

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

ORG_CITY: WOODSIDE

ORG_NAME: LIFE ANALYTICS, INC.

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

PI_NAMEs: FRYE, LAWRENCE J (contact)

PROGRAM_OFFICER_NAME: HARRELL, ERIN

PROJECT_TERMS: Address;Affect;African American;Aging;aging and technology;aging population;Alzheimer's Disease;Alzheimer's disease related dementia;American;associated symptom;Back;Behavior;Biological Markers;Caring;checkup examination;Clinical;Clinical Research;Clinical Trials;cloud based;Code;cohort;commercialization;Communities;Computer software;Computer Systems;Conduct Clinical Trials;cost;dashboard;Data;data access;Data Collection;data exchange;data pipeline;data platform;Data Protection;Dementia;design;Development;digital;Disease;Disease Progression;Documentation;effectiveness research;Elderly;experience;Failure;family management;Frequencies;Funding;gigabyte;Goals;Health;Health Insurance Portability and Accountability Act;Home;improved;Infrastructure;Intervention;Latinx population;Life;Life Style;Location;Longitudinal Studies;Measurement;Measures;Medical;meetings;Memory;migration;Modeling;Monitor;North America;Oregon;Patient Monitoring;Patient Self-Report;Patients;Performance;Phase;Protocols documentation;Provider;Publications;Quality of life;Readiness;remote assessment;Research;research and development;Research Personnel;Rural;Rural Community;Secure;Security;sensor;Side;Site;success;System;Technology;technology platform;Telephone;Testing;Time;United States Department of Veterans Affairs;United States National Institutes of Health;usability

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


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Mental Health;Neurodegenerative;Neurosciences;Parkinson's Disease;Physical Activity

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE Parkinson disease causes significant communication problems that negatively affect quality of life, but there are few viable treatment options. Additionally, the underlying disease pathology mediating these deficits, including the neurotransmitter norepinephrine, is not well understood. The primary outcomes of this research will assess benefits and side effects of treatments for communication and its associated behaviors (cognition, affect) and quantify the contribution of norepinephrine as a viable target to treat these refractory deficits.

PI_NAMEs: CIUCCI, MICHELLE RENEE (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Affect;Affective;Age;Age Months;Anhedonia;Anxiety;Attention;Behavior;Behavior assessment;Behavioral;behavioral response;Biological Assay;Brain;brain behavior;Brain region;Brain Stem;brain tissue;Cardiovascular system;Cell Count;Cell Death;Clinical Trials;Cognition;Cognitive;combat;Communication;Controlled Study;Data Set;Diagnosis;Disease;Disease Progression;Dopamine;dopamine system;dopaminergic neuron;Dysarthria;Emotional;Ethics;executive function;Exercise;experience;Gait;Genetic;Health;High Pressure Liquid Chromatography;Human;Idiopathic Parkinson Disease;Immunohistochemistry;Impairment;improved;in vivo;innovation;Intervention;intervention effect;Intervention Studies;Levodopa;locus ceruleus structure;Measures;Mediating;Memory;Mental Depression;microPET;Modeling;Motor;Nerve Degeneration;neural;neuromechanism;neuron loss;Neurons;neuroprotection;neurotoxicity;Neurotransmitters;neurotrophic factor;noradrenergic;Norepinephrine;norepinephrine system;Outcome;Outcomes Research;Parkinson Disease;Pathology;Patients;Performance;Persons;Pharmaceutical Preparations;PINK1 gene;preclinical trial;primary outcome;Procedures;Propranolol;Quality of life;randomized controlled design;Rattus;receptor;Refractory;Ritalin;Role;Scanning;side effect;social;Socialization;Substantia nigra structure;System;Testing;Therapeutic;Therapeutic Intervention;Time;Translating;treatment center;Treatment Side Effects;vocalization;Withholding Treatment;Work

PROJECT_TITLE: Preclinical trial for dysarthria treatment in Parkinson disease

STUDY_SECTION: MFSR

STUDY_SECTION_NAME: Motor Function, Speech and Rehabilitation Study Section[MFSR]


PHR: Project Narrative We propose to develop a novel technology platform of widespread applicability for elucidation of the protein interactome of any desired RNA species; as well as the identification of specific lncRNAs and their associated proteins/proteoforms that are differentially expressed in aggressive and indolent prostate cancer. These lncRNAs and their interacting proteoforms will be of immediate use as potential prognostic biomarkers to distinguish aggressive and indolent prostate cancers. There are currently over 180,000 prostate cancers diagnosed in the United States annually and differentiating men that need treatment from those with tumors that can be monitored will have a significant economic and quality of life impact on men with this disease. In addition, the delineation of differentially expressed lncRNAs and their associated proteins/proteoforms will provide insight into the biological mechanisms underlying disease progression and provide novel therapeutic targets for further development.

PI_NAMEs: JARRARD, DAVID F.;SMITH, LLOYD M (contact)

PROGRAM_OFFICER_NAME: LI, JERRY

PROJECT_TERMS: Aftercare;Aggressive course;angiogenesis;Apoptosis;Binding;Biological;Biological Assay;Biological Markers;Blood capillaries;c-myc Genes;cancer cell;cancer diagnosis;Cell Differentiation process;Cell Physiology;Cells;Cessation of life;Chromatin;Clinical;Complex;Databases;design;Development;Diagnosis;differential expression;Disease;Disease Management;Disease Progression;Economics;Evaluation;Gene Expression;Genetic Transcription;genomic RNA;Genomics;Grant;Growth;HIV;Human;human tissue;Immunoprecipitation;improved;Individual;Indolent;Informatics;insight;instrument;Invaded;Learning;MALAT1 gene;Malignant neoplasm of prostate;Malignant Neoplasms;Mass Spectrum Analysis;men;Messenger RNA;minimally invasive;Monitor;multiple data types;MYC gene;Nature;Neoplasm Metastasis;new technology;new therapeutic target;novel;Outcome;patient derived xenograft model;Patients;Peptides;Phase;Play;Process;prognostic assays;Prognostic Marker;programs;Prostate-Specific Antigen;Prostatic Neoplasms;protein complex;Proteins;proteomic signature;Proteomics;Quality of life;recruit;Regulation;Research Personnel;Resistance;RNA;RNA Processing;RNA purification;RNA Splicing;RNA-Binding Proteins;Role;Sampling;scaffold;Signal Transduction;Site;Software Tools;Solid Neoplasm;success;System;Techniques;Technology;technology platform;Testing;Time;Tissue Sample;tool;Transcript;transcriptome sequencing;Translations;tumor;United States;Untranslated RNA;Variant;Work

PROJECT_TITLE: Sequence-specific Hybridization Capture for Discovery  of Proteoform–lncRNA Interactions in Prostate Cancer

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Epilepsy;Neurodegenerative;Neurosciences

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Impaired function of the cerebral cortex and cognitive deficits have a large impact on quality of life in people with temporal lobe epilepsy. Understanding the fundamental mechanisms of remote network impairment in focal epilepsy may lead to novel surgical, neurostimulation, or pharmacologic therapies for this disorder.

PI_NAMEs: BLUMENFELD, HAL  (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Accidents;Animals;Anterior Hypothalamus;Arousal;awake;Behavior;behavior test;behavioral impairment;behavioral response;Brain;Cells;Cerebral cortex;Cerebrovascular Circulation;cholinergic;Cognitive deficits;Conscious;cortex mapping;Depressed mood;Development;Disease;Distant;electric impedance;Electroencephalography;Electrophysiology (science);Epilepsy;experimental study;Focal Seizure;Functional Magnetic Resonance Imaging;gamma-Aminobutyric Acid;Glutamates;Head;Hippocampus;Human;Impact Seizures;Impairment;improved;Injury;Lateral;Maps;Measures;Membrane Potentials;Modeling;mouse model;Neocortex;neocortical;Nervous System Disorder;Nervous System Physiology;Neurons;Neurotransmitters;noradrenergic;novel;Operative Surgical Procedures;optogenetics;Partial Epilepsies;Persons;pharmacologic;Physiological;Physiology;Quality of life;Rattus;Role;Seizures;sensor;Site;slow potential;Slow-Wave Sleep;social stigma;Structure;System;Techniques;Temporal Lobe;Temporal Lobe Epilepsy;Thalamic structure;Time;Variant;Whole-Cell Recordings;Work

PROJECT_TITLE: Remote effects of focal hippocampal seizures on neocortical function

STUDY_SECTION: ANIE

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


NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Prevention

PHR: Project Narrative Children with poor early language skills are at risk for academic, social, vocational, and health difficulties across the lifespan. Parent training—as part of early language intervention—is a cost-effective option to address this public health issue, but these interventions demonstrate large individual differences in outcomes and barriers to scalability. The purpose of this research is to examine parent-level predictors of early language interaction quality and modifiability during training, which will help increase intervention effectiveness.

PI_NAMEs: ALPER, REBECCA MAE (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: Address;Adult;Age;Area;autism spectrum disorder;autistic children;Awareness;Behavioral;behavioral clinical trial;career development;Censuses;Child;Child Language;Code;constructivism;cost effective;Data;Development;Disease;dosage;Early Intervention;Educational process of instructing;Effectiveness of Interventions;Environment;experimental study;Family;Goals;Health;Heritability;improved;Individual;Individual Differences;Influentials;Intervention;Intervention Studies;Language;Language Development;Language Development Disorders;Language Disorders;language training;life span;Measures;Mentorship;Modeling;Outcome;Parent-Child Relations;parental role;parenting intervention;Parents;Participant;peer;Play;Populations at Risk;Principal Component Analysis;Problem Solving;programs;Proliferating;Public Health;Reading;Recommendation;Research;Risk;Role;Sampling;scaffold;skills;social;Standardization;Structure;Testing;theories;therapy design;Training;Training Programs;trend;Universities;Vocation

PROJECT_TITLE: Parent-Level Predictors of Early Language Interaction Quality and Intervention Outcomes


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

PHR: The proposed research will conduct the first dose-determination trial to find the optimal number of behavioral counseling sessions (dose) needed to achieve and sustain HIV suppression. The results of this study will determine how much intervention is needed for whom and at what cost to guide health policy and implementation of behavioral interventions designed to improve durable viral suppression.

PI_NAMEs: KALICHMAN, SETH C (contact)

PROGRAM_OFFICER_NAME: STIRRATT, MICHAEL JAMES

PROJECT_TERMS: Adherence;antiretroviral therapy;barrier to care;Behavior Therapy;Behavioral;behavioral clinical trial;Behavioral Model;Behavioral Research;Benchmarking;Binding;Caring;Characteristics;Clinical;Clinical Trials;compliance behavior;cost;Cost Analysis;cost effectiveness;Cost Effectiveness Analysis;Counseling;design;Development;Dose;effective intervention;Emotional;Enrollment;evidence base;Evidence based intervention;flexibility;follow up assessment;Goals;Health;Health Policy;Health Services;HIV;implementation intervention;implementation questions;implementation science;improved;Individual;Informal Social Control;Intervention;Intervention Trial;Life;Link;Literature;longitudinal analysis;Masks;Mental Health;Modeling;Monitor;novel;Outcome;Participant;patient response;patient subsets;Patients;Persons;Plasma;Policies;Policy Maker;Population;Poverty;pragmatic implementation;primary endpoint;programs;Random Allocation;Randomized;Recommendation;Reporting;Research;Resource Allocation;resource guides;Resources;response;scale up;secondary outcome;service providers;skills;social;social determinants;social factors;structural determinants;Subgroup;substance use;Telephone;Testing;theories;therapy adherence;therapy design;Time;Viral;Viral Load result;viral rebound

PROJECT_TITLE: DOSE DETERMINATION TRIAL FOR IMPLEMENTING EVIDENCE-BASEDBEHAVIORAL INTERVENTIONS

STUDY_SECTION: PPAH

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


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

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

ORG_CITY: PROVIDENCE

ORG_DEPT: PATHOLOGY

ORG_NAME: BROWN UNIVERSITY

PHR: NARRATIVE Disorders and diseases of the nervous system are a significant public health concern and result from a combination of health factors, including exposure to environmental toxicants. The goal of this project is to understand how toxicant exposures disrupt the development of parvalbumin interneurons, a critical cell type necessary for learning, memory, information processing, and behavior.

PI_NAMEs: PLAVICKI, JESSICA SUSAN (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: Adult;Affect;age related;Agonist;Alkanesulfonates;Alzheimer's Disease;Aryl Hydrocarbon Receptor;autism spectrum disorder;Behavior;Benzo(a)pyrene;Brain;burden of illness;calcium indicator;Calcium-Binding Proteins;cell type;Chlorpyrifos;Complex;critical period;Data;Development;developmental disease;developmental genetics;Developmental Process;Dioxins;Disease;Embryo;Epilepsy;Equilibrium;Ethers;Etiology;Exposure to;Extracellular Matrix;Functional disorder;gene function;Generations;Genes;Genetic;genetic manipulation;Genetic study;Genetic Transcription;Goals;Health;Homologous Gene;Hyperactivity;Impairment;in vivo;information processing;insight;Intellectual functioning disability;Interneuron function;Interneurons;Invertebrates;Learning;loss of function;Mediating;Memory;Memory impairment;Mental disorders;Modeling;Molecular;Monitor;monobutyl phthalate;National Institute of Environmental Health Sciences;Nervous System Disorder;neural;neural circuit;neuroimaging;Neurons;neurotoxicity;optogenetics;Outcome;Parvalbumins;Pathology;Phenotype;Population;Predisposition;prevent;progenitor;Protein Isoforms;Public Health;Radial;Receptor Activation;Research Personnel;Role;Schizophrenia;Signal Transduction;Source;stem cells;Structure;Testing;Tetrachlorodibenzodioxin;Tissues;tool;Toxic Environmental Substances;toxicant;Toxicant exposure;Transcription Coactivator;transcription factor;Transgenic Organisms;Valproic Acid;Visualization;Visualization software;Work;Zebrafish

PROJECT_TITLE: Toxicant Induced dysregulation of parvalbumin interneuron development and function


ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Mutations in chromatin regulating enzymes are a common feature of many cancer types including lung adenocarcinoma. Our poor understanding of the mechanistic consequences that these mutations have on tumor progression hampers our development of new treatment strategies that exploit molecular vulnerabilities that may exist in these tumors. The overall goal of our project is to identify the molecular aberrations and potential therapeutic vulnerabilities in cancers where SETD2, a chromatin regulating enzyme and tumor suppressor, is inactivated.

PI_NAMEs: FELDSER, DAVID  (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Alleles;Automobile Driving;Biogenesis;Biological Models;Buffers;cancer cell;cancer type;Carbon;Cell division;cell growth;Cell Proliferation;Cell Respiration;Cells;Chromatin;Clinical;clinical efficacy;Consumption;CRISPR/Cas technology;Data;Defect;Development;dietary;Dietary intake;dietary restriction;Disease;Drug Targeting;efficacy evaluation;enzyme mechanism;Enzymes;Frequencies;Gene Expression;Genes;Genetic Transcription;Global Change;Goals;Growth;Histone H3;histone methyltransferase;Histones;Human;Human Cell Line;Hypoxia Inducible Factor;In Vitro;in vivo;inhibitor;Isotope Labeling;KRAS2 gene;KRASG12D;Link;lipidomics;Lipids;loss of function;LoxP-flanked allele;Lung Adenocarcinoma;Lysine;Malignant neoplasm of lung;Malignant Neoplasms;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methionine;Methylation;Methyltransferase;Mitochondria;Molecular;Molecular Abnormality;mouse model;Mus;Mutate;Mutation;neoplastic cell;novel therapeutic intervention;Oncogenic;Oxidative Phosphorylation;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phenotype;Post-Translational Protein Processing;PPAR gamma;pre-clinical;programs;Protein Biosynthesis;Proteomics;Publishing;rational design;Regulation;Regulator Genes;S-Adenosylhomocysteine;S-Adenosylmethionine;Serine;Signal Transduction;Supporting Cell;synthetic lethal interaction;System;Testing;Therapeutic;transcription factor;tumor;tumor progression;Tumor Promotion;Tumor Suppressor Proteins;Work

PROJECT_TITLE: Identifying the Impact of SETD2 Inactivation in Lung Adenocarcinoma

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Heart failure is associated with changes in the surface expression and regulation of the Calcium channel CaV1.2, which contributes to the exertional limitations and propensity for arrhythmia experienced by patients with this disease. Combining APEX proximity labeling with quantitative TMT SPS MS3, I will map the changing “neighborhood” of CaV1.2 in chronic heart failure. Using genetic models of APEX-defined candidate proteins, cellular electrophysiology, and an innovative transgenic mouse model engineered to assess CaV1.2 surface expression, I will gain deep insights into the molecular and cellular pathophysiology of heart failure.

PI_NAMEs: KUSHNER, JARED S (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: 26S proteasome;Adenylate Cyclase;Adrenergic Agents;Adrenergic Agonists;alpha-bungarotoxin receptor;APEX1 gene;Arrhythmia;ascorbate;beta-adrenergic receptor;Binding;Binding Proteins;Binding Sites;Biochemical;Biology;Biotin;Bungarotoxins;Bypass;Cardiac;Cardiac Myocytes;cardioprotection;Cardiovascular Diseases;Cardiovascular Physiology;career development;Congestive Heart Failure;Coupling;Cyclic AMP-Dependent Protein Kinases;Defect;density;desensitization;design;Development Plans;Disease;Disinhibition;Doxycycline;Education;Electrophysiology (science);Engineering;Environment;Enzymes;Exertion;experience;experimental study;extracellular;Flow Cytometry;fluorophore;Forskolin;Frequencies;Functional disorder;Galectin 1;Gene Expression;Genetic;Genetic Models;Goals;Grant;Health;Heart;Heart Diseases;Heart failure;Heart Hypertrophy;improved;inhibitor;innovation;insight;interest;Ion Channel;Knock-out;Knockout Mice;L-type calcium channel alpha(1C);Label;large datasets;Lectin;Ligation;Longevity;Maps;Masks;Mass Spectrum Analysis;Measures;Mediating;Membrane;Mentorship;MG132;Molecular;mouse model;multidisciplinary;Mus;Muscle Cells;Neighborhoods;novel;Organ;Pathway interactions;Patient Care;Patients;Perfusion;Peroxidases;Pharmaceutical Preparations;Phosphodiesterase Inhibitors;Phosphorylation;Physicians;Play;prevent;Probability;Proteasome Inhibitor;protein activation;protein degradation;protein expression;protein reconstitution;Proteins;Proteome;Proteomics;Regulation;Research;Research Project Grants;response;RNA Splicing;Role;Scientist;Shortness of Breath;Signal Pathway;Signal Transduction;Site;skills;success;Surface;Sympathetic Nervous System;Systolic heart failure;Techniques;trafficking;Training;Training Programs;Transgenic Mice;Transgenic Organisms;translational scientist;Ubiquitination;Universities;Up-Regulation;Variant;Work;Writing

PROJECT_TITLE: Regulators and interactomes of CaV1.2 in health and disease

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(OA)]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: Decatur

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: GA

PHR: Cartilage injuries and wear result in progressive deterioration of the cells and matrix of the tissue. These changes typically lead to softening of the matrix immediately surrounding cells and are coupled with a pro- inflammatory environment, triggering aberrant cellular behavior and creating a vicious feedback loop that often culminates in joint-wide osteoarthritis (OA). Cartilage deterioration and OA can be debilitating, causing pain, discomfort, and reduced quality of life; Veterans are more than twice as likely to experience these issues due to trauma and wear-and-tear from service. Thus, the goal of the proposed work is to (1) determine the impact of cartilage fortification of the cellular environment on cellular shape regulation and behavior, (2) establish whether combined fortification and inflammatory inhibition synergistically prevent cartilage breakdown, and (3) utilize a matrix-reinforcing and cell-instructive tissue-penetrating hydrogel to preserve cartilage tissue. Altogether, cellular rehabilitation via our “smart” hydrogel system may delay, or even prevent, the onset of OA.

PI_NAMEs: PATEL, JAY M (contact)

PROJECT_TERMS: Actins;active duty;Affect;Aftercare;Anabolism;antagonist;Anti-Inflammatory Agents;articular cartilage;Articulation;Behavior;Biochemical;Biocompatible Materials;biomechanical test;Biophysics;career;Cartilage;cartilage cell;cartilage degradation;Cartilage injury;Catabolism;cell behavior;Cells;Chemicals;Chondrocytes;Coupled;crosslink;Cues;cytokine;Cytoskeletal Modeling;Cytoskeleton;Defect;Degenerative polyarthritis;Deposition;Deterioration;Environment;Equilibrium;Exhibits;experience;Feedback;Formulation;Fortification;Genotype;Goals;Growth Factor;Health;Homeostasis;Hyaluronic Acid;Hydrogels;improved;In Vitro;in vivo;Inflammation;Inflammatory;inflammatory milieu;injured;Injury;innovation;Instruction;Interleukin-1 Receptors;Intra-Articular Injections;Joints;knee replacement arthroplasty;Knowledge;Lead;Libraries;MADH2 gene;MAP Kinase Gene;Mechanics;mechanotransduction;Mentors;military veteran;Miniature Swine;Modeling;Molecular Biology Techniques;Morphology;multimodality;Nature;novel;novel therapeutic intervention;Outcome;Pain;Palliative Care;Pathway interactions;Penetration;Peptides;peptidomimetics;Phenotype;Positioning Attribute;Predisposition;preservation;prevent;Process;Production;Property;Psychological reinforcement;Quality of life;Regulation;Rehabilitation therapy;Replacement Arthroplasty;Research;response;Route;Services;Shapes;Signal Transduction;Site;skills;Steroids;Structure;System;Testing;Therapeutic;Therapeutic Agents;Therapeutic Effect;Thick;Time;tissue degeneration;Tissue Preservation;Tissues;Training;transmission process;Trauma;Up-Regulation;Veterans;Work

PROJECT_TITLE: Matrix-reinforcing and cell-instructive smart hydrogel for cartilage preservation

STUDY_SECTION_NAME: Career Development Program - Panel I[RRD8]


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

ORG_CITY: CLEVELAND

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: Project Narrative: The purpose of this academic/industrial partnership project is to translate an integrated imaging solution for the detection of residual cancer on or near the surface of the surgical cavity after standard-of-care Breast Conservation Surgery (BCS or “lumpectomy”). Consisting of a quenched, fluorescent probe applied topically in vivo to the surgical cavity, and an FDA-approved imaging instrument (the PDE neo, Hamamatsu Photonics), this technology has the potential to reduce repeat procedure rates due to incomplete resection (currently between 8% and 86%), The final, approved platform will have the potential to significantly reduce healthcare costs due to repeat surgeries, with associated reductions in risks of mortality/morbidity and enhancement in patient quality-of-life.

PI_NAMEs: BASILION, JAMES PETER (contact)

PROGRAM_OFFICER_NAME: GRODZINSKI, PIOTR

PROJECT_TERMS: Academic Medical Centers;acute toxicity;Agreement;Animals;Breast;breast lumpectomy;Breast-Conserving Surgery;cancer cell;Cancerous;Carcinoma;Cessation of life;Clinical;clinical application;clinical imaging;clinical translation;Clinical Trials;Cosmetics;Cyclic GMP;Cytology;Data;Detection;Development;Diffusion;Distant;Dose;Drug Kinetics;European;Evaluation;Excision;experience;FDA approved;first-in-human;Fluorescence;Fluorescent Probes;Formalin;Frozen Sections;Goals;Health Care Costs;healthy volunteer;Home;Hour;Human;Image;image guided;imager;imaging agent;Imaging Device;imaging probe;imaging study;in vivo;industry partner;Infiltration;Malignant Breast Neoplasm;Malignant Neoplasms;Mammaplasty;Mammary Neoplasms;manufacturing capabilities;manufacturing facility;Mastectomy;Maximum Tolerated Dose;Methods;Microscopic;molecular imaging;Molecular Probes;Morbidity - disease rate;mortality risk;next generation;Noninfiltrating Intraductal Carcinoma;novel;novel strategies;Operative Surgical Procedures;optical imaging;Paraffin Embedding;Pathologic;Pathology;Patients;Peptide Hydrolases;Performance;pharmacokinetics and pharmacodynamics;Phase;photonics;Postoperative Period;preclinical imaging;preclinical study;prevent;Procedures;Process;Prognostic Factor;Quality of life;Radiation therapy;Recurrence;Recurrent disease;Repeat Surgery;Residual Cancers;Risk;Risk Factors;Safety;sample fixation;Sampling;Savings;screening;Signal Transduction;Specimen;standard of care;success;Surface;Surgeon;Survival Rate;Techniques;Technology;Testing;Time;Tissue Sample;Tissues;Topical application;Touch sensation;Toxicology;Translating;Translational Research;Translations;tumor;Tumor Tissue;Vascularization;Woman

PROJECT_TITLE: Fluorescence-guided resection of breast tumors using a topically-applied molecular probe

STUDY_SECTION: IPCA

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


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Digestive Diseases;Genetics;Human Genome;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_DEPT: GENETICS

PHR: PROJECT NARRATIVE Defective repair of DNA lesions causes the accumulation of mutations and genomic rearrangements that predispose to cancer development. MCM8 and MCM9 are tumor suppressor genes that promote DNA repair. Understanding the impact of MCM8 and MCM9 cancer-associated mutations on genomic instability will provide novel and important insights into the molecular events that drive tumorigenesis.

PI_NAMEs: CICCIA, ALBERTO  (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: Affect;Alleles;Biochemical;Biological Assay;Biotinylation;BRCA1 gene;BRCA2 gene;Bypass;Cancer Etiology;cancer genomics;cancer type;Cells;Cisplatin;Clustered Regularly Interspaced Short Palindromic Repeats;Colorectal Cancer;Complex;crosslink;Cytoprotection;Defect;Deoxyribonucleases;Development;DNA;DNA analysis;DNA Binding;DNA biosynthesis;DNA Crosslinking Agent;DNA Damage;DNA Double Strand Break;DNA lesion;DNA Repair;DNA Replication Factor;DNA replication fork;DNA Sequence Rearrangement;Double Strand Break Repair;Electron Microscopy;Endometrial Carcinoma;Ensure;Event;Excision;Exhibits;Female;Gastric Adenocarcinoma;Gene Conversion;Genetic;Genetic Recombination;genome editing;genome integrity;Genome Stability;Genomic DNA;Genomic Instability;Goals;Head and Neck Squamous Cell Carcinoma;helicase;homologous recombination;Human Cell Line;In Vitro;Individual;innovation;insight;Invaded;Knowledge;Lesion;life span;Malignant Breast Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mass Spectrum Analysis;Meiosis;Meiotic Recombination;Metabolism;Methodology;Methods;Mitotic;Molecular;Monitor;Mus;Mutation;Myeloproliferative disease;novel;Predisposition;preservation;Primary carcinoma of the liver cells;primary ovarian insufficiency;Property;Prostate Adenocarcinoma;Proteins;Proteomics;recruit;Regulation;repaired;replication stress;Reporting;reproductive;Resistance;response;Role;single molecule;Site;spatiotemporal;Squamous cell carcinoma;Sterility;Structure;superresolution imaging;superresolution microscopy;Syndrome;Technology;tool;tumor;Tumor Suppression;Tumor Suppressor Genes;Tumor Suppressor Proteins;tumorigenesis;Visualization;Woman

PROJECT_TITLE: Regulation of DNA synthesis in response to DNA damage

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


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);Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences

PHR: NARRATIVE The blood brain barrier (BBB) is a very important structure that regulates the transport of many molecules that are critical for brain function and health. Endothelial cells, pericytes and astrocytes and critical cells in the formation and maintenance of the BBB and in the regulation of transport of molecules into the brain. However, there are very few tools to study these cells and transport mechanisms in vivo, especially in humans. We have discovered a group of molecules that we think can be used to develop probes to selectively deliver drugs and image these cells in animals and humans. In this proposal we will characterize in depth how these probes work and will do proof of principle experiments to determine their potential as cell specific probes in mice and humans. Finally, we will test the properties of the probes in Alzheimer's disease and stroke mouse models.

PI_NAMEs: GRUTZENDLER, JAIME  (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Address;Affinity;Alzheimer's Disease;Alzheimer's disease model;animal imaging;Animals;Astrocytes;Blood;Blood - brain barrier anatomy;Blood Cells;blood-brain barrier function;Brain;brain cell;Brain imaging;Brain Ischemia;brain surgery;Calcium;Capillary Endothelial Cell;Cell Communication;cell type;Cells;cellular imaging;Cellular Structures;chemical synthesis;Chemicals;Complex;CRISPR/Cas technology;Cytoplasm;Data;Databases;Development;Diagnostic;Disease;Drug Carriers;Drug Compounding;Drug Delivery Systems;Electroporation;Endothelial Cells;experimental study;fluorophore;functional group;Future;Health;Homeostasis;Human;human imaging;Hybrids;Image;improved;in utero;In Vitro;in vivo;in vivo optical imaging;interdisciplinary approach;Ions;Knockout Mice;Knowledge;Label;Libraries;Maintenance;Membrane Transport Proteins;Molecular;Molecular Probes;mouse model;Movement;Mus;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;Neurosciences Research;neurovascular unit;novel;Nutrient;optical imaging;Organic Cation Transporter;overexpression;Pathogenesis;Pathology;Pattern;Penetration;Pericytes;Permeability;Pharmaceutical Preparations;pharmacologic;Plasmids;Play;Positron-Emission Tomography;Property;Radiopharmaceuticals;radiotracer;Regulation;Resolution;RNA;Role;Route;screening;selective expression;small molecule;small molecule libraries;solute;Specificity;Stroke;Structure;targeted delivery;Testing;Therapeutic;Therapeutic Agents;tool;tool development;Toxin;Tracer;trafficking;transcriptome;translational neuroscience;Translational Research;Transmembrane Transport;Transport Process;two-photon;uptake;Water;Work

PROJECT_TITLE: Molecular probes to image and target the neurovascular unit in health and disease


NIH_SPENDING_CATS: Aging;Brain Disorders;Climate-Related Exposures and Conditions;Clinical Research;Genetics;Neurodegenerative;Neurosciences;Parkinson's Disease;Prevention;Social Determinants of Health;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE This work seeks to understand how environmental factors, specifically pesticides, influence the development of Parkinson's Disease (PD) at the level of effects on dopaminergic neurons, the critical cell population lost in PD. Goals of the work include testing how specific pesticides cause damage to neurons derived from PD patient stem cells, and how that damage is influenced by astrocytes and microglia—two other influential central nervous system cell types. Finally, we will begin to set the stage in this proposal for performing “epidemiology in a dish”, growing the stem cells of many PD patients at once, to ultimately test which genetic factors render patients susceptible to pesticides in the first place.

PI_NAMEs: KROLEWSKI, RICHARD CARL (contact)

PROJECT_TERMS: Academic Medical Centers;Affect;alpha synuclein;alpha Tubulin;Astrocytes;attributable risk;Binding;Biology;Blood - brain barrier anatomy;Brain;Calcium Signaling;California;career;career development;Cell Line;cell type;Cells;Censuses;Central Nervous System;Chairperson;Clinic;cohort;Collaborations;Complex;Computing Methodologies;Coupled;Coupling;Cytokine Signaling;Cytoskeleton;Data;design;Detection;Development;Development Plans;Disease;disease phenotype;disease-in-a-dish;disorder risk;Disparate;dopaminergic neuron;Dropout;endophenotype;Ensure;Environment;Environmental Exposure;Environmental Risk Factor;Epidemiology;Etiology;Evaluation;Exposure to;Gene Dosage;gene environment interaction;Genes;Genetic;genetic risk factor;Genetic Transcription;Goals;Grouping;Growth;Health;Hospitals;Idiopathic Parkinson Disease;In Vitro;induced pluripotent stem cell;Industrialization;Inflammation Mediators;Influentials;Institution;Link;man;member;Mentorship;Metabolism;Methods;Microglia;Midbrain structure;Mitochondria;Modeling;Mutation;mutation correction;Nerve Degeneration;Neuroglia;Neuroimmune;Neurology;neuron loss;neuronal survival;Neurons;neuroprotection;neurotoxicity;Organelles;pandemic disease;Paracrine Communication;Paraquat;Parkinson Disease;Pathologic;Pathology;patient derived induced pluripotent stem cells;Patients;Penetrance;pesticide exposure;pesticide interaction;Pesticides;Phenotype;Physicians;Population;Positioning Attribute;Predisposition;prevent;Process;Production;progression marker;Public Health;Quality Control;Reporter;Reporting;Research;Research Personnel;Research Training;Resources;response;Risk;Risk Factors;Role;Sampling;Scientist;screening;Signaling Molecule;single-cell RNA sequencing;sporadic Parkinson's Disease;stem cells;success;synergism;System;Testing;Toxic effect;toxicant;translational neuroscience;Trifluralin;Tyrosine 3-Monooxygenase;Universities;Woman;Work

PROJECT_TITLE: Investigating environmental and gene-environment contributors to Parkinson's disease risk by coupling quantitative environmental exposure data to iPSC modeling


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: PROJECT NARRATIVE Here we propose to develop a dynamic hydrogel that mimics the complex, multivariate cues of the native ECM to guide the self-assembly of vascular networks from a single cell type. With this biomaterial approach, we aim to control the vasculogenic potential of induced pluripotent stem cell-derived endothelial progenitor cells (iPSC- EPs) and develop a personalized tissue-engineered neovascularization strategy as a clinically viable treatment for peripheral arterial disease treatment. Such a system with superior precision and control of biophysical and spatiotemporal parameters has the potential to revolutionize current methods for creating vascularized tissue for therapy and disease modeling.

PI_NAMEs: ZOLDAN, JANETA  (contact)

PROGRAM_OFFICER_NAME: LUNDBERG, MARTHA

PROJECT_TERMS: 3-Dimensional;Anastomosis - action;Architecture;Behavior;Binding Sites;Biocompatible Materials;Biological;Biophysics;bioscaffold;Blood capillaries;Blood flow;Blood Vessels;Cardiovascular system;cell assembly;cell type;Cells;Clinic;Clinical;Collagen;Complex;computational pipelines;Coupled;Coupling;critical limb Ischemia;crosslink;Crosslinker;Cues;Data;density;Development;disease model;dithiol;Elasticity;endothelial stem cell;Endothelium;Engineering;Engraftment;Extracellular Matrix;Generations;Goals;Health;Hindlimb;human induced pluripotent stem cells;Hyaluronic Acid;Hybrids;Hydrogels;Implant;improved;In Situ;In Vitro;in vivo;individualized medicine;induced pluripotent stem cell;Ischemia;Lead;limb amputation;limb ischemia;Mechanics;Mediating;Metalloproteases;Methods;Modeling;Molecular;Morbidity - disease rate;Morphogenesis;necrotic tissue;neovascular;neovascularization;non-invasive monitor;Outcome;Patients;Peptides;Peptoids;Perfusion;Pericytes;Peripheral;Peripheral arterial disease;polarized cell;Population;Predisposition;preservation;Process;Property;Reaction;Recovery;Regulation;response;self assembly;Self Direction;Shapes;Skin;spatiotemporal;stem cell engraftment;stem cells;Stimulus;Structure;System;Testing;Therapeutic;therapeutically effective;Time;Tissue Engineering;Tissue Therapy;Tissues;Traction;Vascularization;vasculogenesis;Vasculogenic;Work

PROJECT_TITLE: Dynamic ECM-Mimicking Biomaterials for Ischemia Treatment

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


NIH_SPENDING_CATS: Charcot-Marie-Tooth Disease;Disability Research;Genetics;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Rare Diseases

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Narrative This study examines the various effects of Schwann cell pathology on the structure and function of axons in nerve conduction, using genetically modified mice that model inherited human neuropathies. Unexpectedly, these mutations demonstrate that failure to form myelin is not the chief cause of their neurological disability but rather, other factors, including inflammation of their nerves, are critical. Determining how these mutant Schwann cells differentially impact axon biology and nerve inflammation should aid in developing new therapeutic strategies for peripheral neuoropathies.

PI_NAMEs: SALZER, JAMES  (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Action Potentials;Affect;Age Months;Axon;Basal lamina;Biology;Cell Nucleus;cellular pathology;Charcot-Marie-Tooth Disease;Clinical;clinical phenotype;Collagen;conditional knockout;Cyclic AMP;Defect;Diameter;differential expression;disability;Disease;Distal;dysmyelination;EGR2 gene;Exhibits;Failure;Fiber;G-Protein-Coupled Receptors;Gene Modified;Genetic Transcription;Human;Inflammation;inflammatory milieu;Inflammatory Response;Inherited;insight;Laminin Receptor;life span;Macrophage;Maintenance;Minor;mouse model;Mus;mutant;Mutant Strains Mice;Mutation;Myelin;Myelin Sheath;myelination;Nerve;nerve injury;Nervous System Physiology;Neural Conduction;neuroinflammation;Neurological disability;Neuropathy;neurotransmission;novel therapeutic intervention;Paralysed;Pathogenesis;Pathologic;Pathology;Pathway interactions;Peripheral;Peripheral Nerves;Peripheral Nervous System Diseases;pharmacologic;Phenotype;Population;Proteins;Radial;Ranvier's Nodes;Regulation;Role;Schwann Cells;sciatic nerve;Series;Severities;Signal Transduction;Structure;Testing;Thick;transcription factor;transcriptome;transcriptome sequencing

PROJECT_TITLE: Impact of Schwann Cell Pathology on Axon Structure and Function

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Skin Cancer

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: This proposal is aimed at developing new treatments that will significantly improve the outcome of patients with colorectal cancer. It is based on the idea that clinical efforts to inhibit ERK signaling in colorectal cancer have been limited by insufficient target inhibition due to the high basal receptor driven RAS activation in the colorectum. We plan to profoundly inhibit ERK by co-targeting ERK activation and receptor re-activation and by using novel combinations and dosing schedules that expand the therapeutic index of ERK inhibition.

PI_NAMEs: YAEGER, RONA  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Adaptor Signaling Protein;Advanced Malignant Neoplasm;Attenuated;Binding;Biochemical;BRAF gene;Cancer Etiology;Cells;Cessation of life;Clinic;Clinical;clinical development;Cloning;colon cancer patients;Colorectal;Colorectal Cancer;colorectal cancer treatment;Data;Development;dimer;DNA Sequence Alteration;Dose;efficacy evaluation;efficacy testing;Environment;Epidermal Growth Factor Receptor;Epigenetic Process;Epithelium;Feedback;Genomics;Goals;Growth;improved outcome;In Vitro;in vivo;in vivo Model;Incidence;inhibitor;Keratinocyte cancer;Kinetics;Ligands;Lung Carcinoma;Mediating;MEKs;Melanoma;Minority;Modeling;Molecular Profiling;mutant;Mutation;NF1 gene;NF1 mutation;Normal tissue morphology;novel;Oncogenes;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Pattern;Phosphotransferases;preclinical evaluation;pressure;Proliferating;Property;Proteins;PTPN11 gene;RAF1 gene;receptor;Receptor Protein-Tyrosine Kinases;Recurrence;Resistance;resistance mechanism;response;Role;Sampling;Schedule;Series;Signal Pathway;Signal Transduction;targeted treatment;Testing;Therapeutic Index;Toxic effect;tumor;tumor growth

PROJECT_TITLE: Exploiting the distinct genomics and signaling of colorectal cancers to effectively target ERK

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Immunotherapy;Pancreatic Cancer;Rare Diseases

ORG_CITY: Newark

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative Tumor associated macrophages (TAMs) play an important role in tumor progression, metastasis, immune suppression and therapy resistance, but their function in oncogenic KRAS inhibition resistance is largely unknown. Preliminary study suggests that, forced expression of HDAC5 in pancreatic cancer cells promotes active recruitment of TAMs, which provide TGFβ to support oncogenic KRAS independent tumor growth. This proposal aims to investigate the necessity of tumor-TAMs crosstalk in the bypass of KRAS dependency and explore the therapeutic potentials by co-targeting KRAS and HDAC5-TAM-TGFβ axis in pancreatic cancer.

PI_NAMEs: HOU, PINGPING  (contact)

PROGRAM_OFFICER_NAME: JAKOWLEW, SONIA B

PROJECT_TERMS: Advisory Committees;antitumor effect;Bioinformatics;Bypass;Cancer Center;cancer therapy;career development;Cell Maintenance;Cell Survival;Cells;Chemicals;Clinical;clinical development;Co-Immunoprecipitations;Collaborations;Complex;cytokine;Data;Data Set;Dependence;dimensional analysis;disorder control;Doxycycline;Environment;Epigenetic Process;Faculty;gain of function;Genetic;Goals;HDAC5 gene;Head;Heterogeneity;Human;Immunology;Immunosuppression;Immunotherapy;Impairment;improved;In Vitro;in vivo;independency;Infiltration;inhibitor;insight;Institution;K22 Award;Knock-out;KRAS oncogenesis;KRAS2 gene;KRASG12D;Laboratories;loss of function;Macrophage;MADH3 gene;MADH4 gene;Malignant neoplasm of pancreas;Malignant Neoplasms;Mass Spectrum Analysis;Medical Research;Mentors;Modeling;Molecular;mouse model;Mus;mutant;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;Oncogenes;Pancreas;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;pancreatic ductal adenocarcinoma model;Pathway interactions;patient derived xenograft model;Patients;Pharmacologic Substance;Phenotype;Physicians;Pilot Projects;Play;Positioning Attribute;Postdoctoral Fellow;preclinical development;prevent;programs;Publications;receptor;recruit;Recruitment Activity;Recurrent disease;Regulation;Relapse;Research;Research Personnel;Resistance;response;Role;S100A8 gene;Scientist;screening;Signal Transduction;single-cell RNA sequencing;skills;Students;synergism;targeted cancer therapy;targeted treatment;Therapeutic;TP53 gene;transcriptome;Transforming Growth Factor beta;translational study;tumor;tumor growth;tumor heterogeneity;tumor progression;Tumor-associated macrophages;Up-Regulation;Writing;Xenograft Model

PROJECT_TITLE: Tumor-TAMs crosstalk enables bypass of oncogenic KRAS dependency in pancreatic cancer

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Transition to Independence Study Section (I)[NCI(B)-I]


NIH_SPENDING_CATS: Autoimmune Disease;Biodefense and Related Countermeasures;Biotechnology;Brain Disorders;Clinical Research;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Immunotherapy;Infectious Diseases;Neurosciences;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are increasingly recognized to be suffering from a wide variety of central nervous system complications. This project leverages an innovative and high-throughput pipeline for high resolution mapping of anti-viral antibodies and human proteome-wide detection of autoantibodies from sera and cerebrospinal fluid collected from COVID-19 patients to better understand neuropathogenesis and provide insights into neural mechanisms that underly complex brain functions ranging from coordination to maintenance of mood and personality. Generation of monoclonal antibodies from clonally expanded B cells in the cerebrospinal fluid of COVID-19 patients will enable in vivo mouse studies to deepen our understanding of the potential pathogenic role these antibodies play.

PI_NAMEs: PLEASURE, SAMUEL JEREMY;WILSON, MICHAEL R (contact)

PROJECT_TERMS: 2019-nCoV;Acute;acute flaccid myelitis;adaptive immune response;Adult;Anatomy;Animal Disease Models;Animal Model;animal model development;Anti-viral Agents;Antibodies;Antibody Repertoire;Antigens;Autoantibodies;Autoantigens;Autoimmune;Autoimmune encephalitis;Autoimmunity;B-Lymphocytes;Behavioral Assay;biobank;Biological Assay;Biological Markers;biomarker identification;Blood;Brain;brain tissue;Cell Separation;Cells;Central Nervous System;Cerebrospinal Fluid;Child;Chronic;Clinical;clinical care;clinical center;Clinical Management;clinical phenotype;Clinical Research;clinically actionable;Clonal Expansion;cohort;Collaborations;Complex;Coronavirus;COVID-19;COVID-19 complications;COVID-19 patient;Cross Reactions;cross reactivity;Data;Detection;Development;Disease;Encephalitis;Encephalopathies;Enrollment;Epitope Mapping;experimental study;extracellular;Functional disorder;General Hospitals;Generations;Goals;Guillain Barré Syndrome;Hospitalization;Human;human coronavirus;Humoral Immunities;Immune;Immune response;Immunofluorescence Immunologic;Immunoprecipitation;Immunosuppression;Immunotherapy;in vivo;Infection;Inflammation;Inflammatory;Infrastructure;Infusion procedures;innovation;insight;Laboratories;Laboratory Finding;Maintenance;Maps;Mass Spectrum Analysis;Medical center;men;Metagenomics;microbial;Molecular;Molecular Mimicry;Monoclonal Antibodies;monoclonal antibody production;Moods;Multiple Sclerosis;Mus;neural;Neuroanatomy;neuroinflammation;Neurologic;neurologic sequelae of COVID-19;Neurologist;neuromechanism;Neuropathogenesis;next generation sequencing;novel;novel coronavirus;Nucleic Acids;Outpatients;overexpression;Pathogenesis;pathogenic autoantibodies;Pathogenicity;Patients;Pediatric Hospitals;Peripheral Nervous System;Personality;Phage Display;Phage ImmunoPrecipitation Sequencing;Phenotype;Plasma Cells;Play;pleasure;post-COVID-19;Production;prospective;Proteome;Protocols documentation;Resolution;RNA;Rodent;Role;Sampling;San Francisco;SARS-CoV-2 antibody;SARS-CoV-2 infection;SARS-CoV-2 spike protein;Scientist;screening;Seminoma;Sensitivity and Specificity;Stains;Steroids;Syndrome;Testing;Tissues;treatment response;treatment strategy;United States National Institutes of Health;Universities;Viral;Viral Antibodies;viral detection;Virus Diseases;Work

PROJECT_TITLE: Humoral Immune Mechanisms of Acute and Chronic Neurologic Sequelae of COVID-19

STUDY_SECTION: CNBT

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: STONY BROOK

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: PROJECT NARRATIVE: This proposal investigates a novel idea to explain some aspects of both the initiation of neurodegeneration and dementia diseases, and the spread of disease pathology, in the central nervous system. Based on prior evidence from our lab, our collaborators, and other researchers, we have evidence that elements within our own genomes, namely retrotransposons and endogenous retroviruses, become activated during aging and during initiation of neurodegenerative disease, both through known and unknown causes. This proposal will test the ideas that protein pathologies, specifically in the protein TDP-43, can have a causative role in releasing activity in previously suppressed retroviruses, which can then lead to disease mechanisms within affected cells, and to spread of disease between cells in the brain.

PI_NAMEs: SHER, ROGER B (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Affect;Aging;ALS pathology;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Amyotrophic Lateral Sclerosis;Anti-Retroviral Agents;Astrocytes;Automobile Driving;Autopsy;Biochemistry;Bioinformatics;Biological Assay;Biology;Brain;Brain region;cell type;Cells;Cellular Assay;Central Nervous System;Cytoplasm;Dementia;derepression;Development;Disease;disease phenotype;Disease Progression;Distal;DNA Damage;DNA Repair;Drosophila genus;Elements;Endogenous Retroviruses;Event;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;Gene Expression Profile;Genome;Glial Fibrillary Acidic Protein;Human;Inflammation;Injections;L1 Elements;Measures;Mediating;Microglia;Modeling;Molecular;Motor;Motor Cortex;motor disorder;Motor Neurons;mouse model;Mus;Mutant Strains Mice;Nerve Degeneration;neuroblastoma cell;Neurodegenerative Disorders;Neuroglia;Neurologic;Neurons;neurotoxic;novel;Nuclear;Nuclear Protein;Oligodendroglia;overexpression;Pathologic;Pathology;Pathway interactions;Patients;promoter;protein aggregation;protein TDP-43;Proteins;Reporter;Research Personnel;Retrotransposon;Retroviridae;Reverse Transcriptase Inhibitors;Role;Signal Pathway;Signal Transduction;Site;Source;Spinal;Stavudine;System;Testing;Tissues;Toxic effect;transcriptome sequencing;Transgenic Mice;Translational Research;Virus

PROJECT_TITLE: Effects of TDP-43 Proteinopathy on Retrotransposon Activation and Cell-Type Specific Vulnerability in a Mammalian Model of Alzheimer's and Related Dementias


ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Cervical Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;HPV and/or Cervical Cancer Vaccines;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Immunization;Infectious Diseases;Pediatric;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Rare Diseases;Rural Health;Sexually Transmitted Infections;Social Determinants of Health;Vaccine Related;Women's Health Research

ORG_CITY: ROCHESTER

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Despite an effective HPV vaccine being available in the US since 2006, uptake is well below the Healthy People 2030 goal of 80%. We will test the effect of standing orders plus communication training for providers and staff compared to communication training alone on HPV vaccination rates. The goal is to understand how best to increase HPV vaccination in primary care, to ultimately reduce HPV-related cancers.

PI_NAMEs: RAND, CYNTHIA M (contact)

PROGRAM_OFFICER_NAME: CHOLLETTE, VERONICA

PROJECT_TERMS: 12 year old;13 year old;17 year old;Accountability;accountable care organization;Adolescent;Adult;Affect;Age;age group;aged;Area;arm;Authorization documentation;Black race;booster vaccine;Caring;Clinical;Cluster randomized trial;Communication;comparison control;cost;cost effective;cost effectiveness;Cost Measures;Data;Data Analytics;data infrastructure;Decision Making;Dose;Education;effectiveness evaluation;Effectiveness of Interventions;Eligibility Determination;Ensure;Exposure to;Feedback;Goals;Health;health disparity;Hispanic;HPV vaccine acceptance;HPV vaccine hesitancy;Human papilloma virus infection;Human Papilloma Virus Vaccination;Human Papilloma Virus Vaccine;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Immunization;immunoreaction;implementation measures;improved;influenza virus vaccine;Inpatients;Intervention;Interview;Leadership;Left;Malignant neoplasm of cervix uteri;malignant oropharynx neoplasm;Medical Care Team;member;men;Methods;Motivation;New York;Nurses;organizational readiness;pandemic disease;parental influence;Parents;Patients;Patients' Rooms;pediatric patients;Persons;Physicians;Play;Policies;Poverty;practice factors;Primary Care;primary care practice;primary care setting;programs;Protocols documentation;Provider;provider factors;randomized trial;Recommendation;recruit;Resources;Running;rural area;Rural Population;Schools;Structure;suburb;Surveys;Testing;Time;Training;treatment arm;Underserved Population;uptake;Vaccinated;Vaccination;vaccine acceptance;Vaccines;Visit;Woman;Work;Writing

PROJECT_TITLE: Standing Orders to Improve HPV Vaccination

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases

PHR: Project Narrative This proposal seeks to elucidate the immunosuppressive mechanism of Siglec-15, a novel PD-L1 mutually exclusive T cell immune checkpoint, on the regulation of myeloid cell responses and the identification of its functional receptors on both myeloid cells and T cells. We will further characterize its potential cancer-associated induction mechanism and strategies to improve Siglec-15-targeted therapeutic responses in anti-PD-1- insensitive cancers. The successful completion of our proposed studies will provide important insights to improve the efficacy of our established clinical program and suggest new approaches for next-generation cancer immunotherapies.

PI_NAMEs: WANG, JUN  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: Ablation;Anti-CD40;anti-PD-1;anti-PD-1/PD-L1;Antibodies;antigen-specific T cells;Binding;Bioinformatics;Biological Assay;cancer cell;cancer immunotherapy;Cancer Model;Cancer Patient;cancer therapy;cancer type;Cell Culture System;Cell Physiology;Cells;checkpoint receptors;Clinic;Clinical;clinical translation;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;combinatorial;cytokine;Data;Databases;Down-Regulation;Ectopic Expression;Exhibits;first-in-human;Genetic;genome-wide;Human;Human Genome;Immune;immune cell checkpoints;immune checkpoint;immune checkpoint blockade;immune function;immune modulating agents;Immunomodulators;immunoregulation;Immunosuppression;Immunosuppressive Agents;Immunotherapy;improved;In Vitro;in vivo;Infiltration;inhibitor;insight;Interferon Type II;Interleukin-6;Knock-out;KRAS oncogenesis;KRAS2 gene;KRASG12D;Ligands;Macrophage;Macrophage Colony-Stimulating Factor;Malignant neoplasm of ovary;Malignant neoplasm of pancreas;Malignant Neoplasms;Membrane Proteins;Meta-Analysis;Modeling;Molecular;Monoclonal Antibodies;mouse model;Mus;mutant;Mutation;Myelogenous;Myeloid Cell Activation;Myeloid Cells;next generation;novel;novel strategies;Organoids;pancreatic cancer model;Pathway interactions;patient subsets;Patients;Pattern;PD-1/PD-L1;Phase I/II Clinical Trial;Phenotype;phosphatidylinositol 3-kinase gamma;Pilot Projects;programmed cell death ligand 1;programmed cell death protein 1;programs;receptor;Refractory;refractory cancer;Regulation;Reporting;Resistance;response;Role;Safety;selective expression;Serous;Shapes;sialic acid binding Ig-like lectin;sialic acid receptor;Signal Transduction;single-cell RNA sequencing;small molecule inhibitor;Solid;standard of care;success;synergism;T cell response;T-Lymphocyte;targeted treatment;Testing;Therapeutic;therapeutic evaluation;Toxic effect;TP53 gene;transcription factor;transcriptome sequencing;Treatment Efficacy;treatment response;tumor;tumor growth;Tumor Immunity;tumor immunology;tumor microenvironment;Tumor-associated macrophages;tumorigenic;Up-Regulation

PROJECT_TITLE: Elucidating the Immune Suppressive Mechanism of SIGLEC-15 in the Tumor Microenvironment

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


NIH_SPENDING_CATS: Cancer;Genetics

ORG_NAME: WISTAR INSTITUTE

PHR: Project Narrative  The  proposed  research  will  conduct  the  first  comprehensive  analysis  designed  to  definitively  assess  the  influence of the codon 72 SNP on mutant p53 GOF, and on the efficacy of p53- refolding compounds.  It  will also define the impact of the Y107H African- specific SNP within the p53 DNA binding domain on p53  structure and function using NMR and a novel mouse model.  This research has important implications for  understanding  cancer  risk  in  under- represented  populations,  and  for  informing  personalized  medicine  approaches.

PI_NAMEs: MURPHY, MAUREEN E. (contact)

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Address;African;African American population;African ancestry;Alleles;Arginine;Biochemical;Biology;Cancer Biology;Cancer Institute of New Jersey;cancer risk;cancer therapy;caucasian American;Chromatin Remodeling Factor;Clinical Trials;clinically relevant;Code;Codon Nucleotides;cytotoxicity;Data;design;DNA Binding Domain;ethnic bias;ETS2 gene;follow-up;Fox Chase Cancer Center;frontier;functional improvement;gain of function;gain of function mutation;Gene Combinations;Gene Expression;Genes;Genetic Polymorphism;Genetic Transcription;Growth;Human;Impairment;In Vitro;in vivo;in vivo evaluation;Investigation;Knowledge;Learning;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;Mediator;Metabolism;Minor;minority health disparity;Missense Mutation;Molecular;Molecular Conformation;mouse model;mutant;mutant mouse model;Mutate;Mutation;Neoplasm Metastasis;neoplastic cell;novel;Oncogenes;Oncogenic;Pathogenicity;Pathway interactions;personalized medicine;Pharmaceutical Preparations;Population;Prognosis;Proline;Protein Degradation Induction;protein function;protein protein interaction;Proteins;PTEN gene;Publishing;recruit;Reporting;Research;Research Personnel;Role;Sampling;Single Nucleotide Polymorphism;Structure;Testing;The Cancer Genome Atlas;Therapeutic;tool;TP53 gene;Transactivation;treatment response;tumor;Tumor Biology;tumor growth;tumor metabolism;tumor progression;Tumor Suppression;Tumor Suppressor Genes;Tumor Suppressor Proteins;Tumor-Derived;Underrepresented Populations;Variant;Woman;Work

PROJECT_TITLE: The impact of coding region variants on mutant p53 biology


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Nanotechnology;Neurosciences;Orphan Drug;Radiation Oncology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: JACKSONVILLE

ORG_NAME: MAYO CLINIC  JACKSONVILLE

ORG_STATE: FL

PHR: This proposal aims to evaluate the translational potential of a proprietary tumor-targeted liposomal (TTL) formulation combining a new generation of neuropilin-1 inhibitor having better efficacy and pharmacokinetic parameters and everolimus in a single payload, via preclinical evaluation in multiple relevant mouse models of Glioblastoma Multiforme (GBM). Additionally, a local administration of the liposomes entrapped in a hydrogel system will be compared with systemic administration of the liposomes in an established resection model where the primary tumor will be taken out by surgery before initiating treatment. The most effective formulation will be used for pharmacokinetic and preliminary toxicity studies as a stepping stone for future IND application and potential clinical trials seeking to benefit GBM patients as well as patients suffering from other types of drug-resistant cancer.

PI_NAMEs: MUKHOPADHYAY, DEBABRATA ;QUINONES-HINOJOSA, ALFREDO  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Address;Animal Model;Animals;Biodistribution;blood-brain barrier crossing;Brain Neoplasms;cancer type;Cell Line;Cells;chemoradiation;Chemoresistance;Chemotherapy and/or radiation;Clinical;Clinical Trials;clinically relevant;comparative;Cytometry;Data;Delayed-Action Preparations;digital;Disease;Drug Delivery Systems;Drug Formulations;Drug Kinetics;drug release kinetics;Drug resistance;Drug Targeting;effective therapy;efficacy evaluation;efficacy testing;Evaluation;Excision;Formulation;Future;Generations;Glioblastoma;Glioma;Growth;Human;Hydrogels;Immunocompetent;improved;In Situ;In Vitro;in vivo;in vivo Model;inhibitor;Injections;Invaded;Laboratories;Lead;liposomal formulation;Liposomes;Local Therapy;Malignant neoplasm of brain;Malignant Neoplasms;Mediating;Modeling;mouse model;mTOR Inhibitor;Mus;nanoformulation;Nanotechnology;nanotechnology platform;Neuropilin-1;novel;Operative Surgical Procedures;Outcome;Patients;Pharmaceutical Preparations;Pharmacodynamics;Phenotype;Pre-Clinical Model;preclinical evaluation;prevent;Primary Neoplasm;Process;Prognosis;Radiation;radiation resistance;Radiation therapy;Radiation Tolerance;radioresistant;Recurrence;Recurrent tumor;refractory cancer;Regimen;Reporting;Research;Resistance;Role;SDZ RAD;side effect;Signal Pathway;small molecule;Solubility;standard care;stemness;Surgically-Created Resection Cavity;System;Systemic Therapy;targeted delivery;targeted treatment;Techniques;temozolomide;Testing;Therapeutic;therapeutically effective;therapy outcome;therapy resistant;Toxic effect;Toxicology;translational potential;treatment strategy;tumor;tumor growth;tumor initiation;tumor-immune system interactions;United States National Institutes of Health;Validation;Vascular Endothelial Growth Factors;Water;Work;Xenograft procedure

PROJECT_TITLE: Tumor targeted drug delivery nanoplatform to overcome therapy resistance glioblastoma