ORG_CITY: STANFORD

ORG_DEPT: GENETICS

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: Project Narrative T cells recognize diseased cells via molecular interactions between T cell receptors (TCRs) and peptides presented by MHC molecules (pMHCs), and an improved ability to predict which pMHC/TCR pairs drive strong T cell responses could improve our ability to engineer personalized anti-cancer therapies without dangerous side effects. T cell crawling during immunosurveillance applies biomechanical forces to pMHC/TCR complexes that are crucial for sensitive and specific recognition, with activating pMHC/TCR pairs forming ‘catch’ bonds that strengthen under force, but current screening methods test pMHC/TCR binding in the absence of force and thus fail to predict potent agonists in vivo. Here, I will develop new microfluidic technologies that make it possible to systematically interrogate 10000s of pMHC/TCR complexes for their ability to form catch bonds and drive potent T cell activation, generating critical new tools and quantitative training data in the fight against cancer.

PI_NAMEs: FORDYCE, POLLY MORRELL (contact)

PROGRAM_OFFICER_NAME: JOHNSON, ERIC MICHAEL

PROJECT_TERMS: Address;Affinity;Agonist;Alleles;Amino Acids;Antigen-Presenting Cells;antigen-specific T cells;Binding;Biomechanics;cancer immunotherapy;cancer therapy;Cancerous;Cell surface;Cells;Clone Cells;Complex;cost;cytotoxic;Dangerousness;Disease;Encapsulated;engineered T cells;Engineering;fighting;Hour;Immune response;Immunologic Surveillance;Immunotherapy;improved;In Vitro;in vivo;invention;Malignant Neoplasms;Methods;microfluidic technology;Microfluidics;neoantigens;new technology;next generation sequencing;novel;Patients;Peptide Receptor;Peptide Vaccines;Peptides;Physiological;Play;Proteins;Qualifying;receptor binding;Recombinants;Role;screening;Sensitivity and Specificity;side effect;Sorting;Surface;T cell response;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;TCR Activation;Techniques;Technology;Testing;tool;training data;Transfusion;Tumor Antigens;Work

PROJECT_TITLE: Using microfluidics to realize patient-specific anti-cancer immunotherapies


ADMINISTERING_IC: CA

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: HOUSTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

ORG_STATE: TX

PHR: Project 3 NARRATIVE Angiogenesis is essential for tumor growth; several anti-angiogenesis drugs including bevacizumab have been approved for clinical use but have shown only modest efficacy. This necessitates development of new anti- angiogenesis therapies. Elevated EGFL6 was reported in ovarian cancer but not in normal adult tissues; our preliminary studies showed that EGFL6 blockade in ovarian cancer models resulted in significant reduction in tumor burden without affecting wound healing. The proposed work could have significant implications for development of new anti-EGFL6 based therapies in ovarian cancer.

PI_NAMEs: SOOD, ANIL K (contact)

PROJECT_TERMS: Adult;Adverse event;Affect;Aftercare;angiogenesis;Angiogenesis Inhibitors;antiangiogenesis therapy;Antibodies;antitumor effect;Area;bevacizumab;Biological;Biopsy;Blood Vessels;cancer cell;Cancer Model;cancer therapy;CD4 Positive T Lymphocytes;CD8B1 gene;chemotherapy;Clinical;Collection;Complex;Computer software;Data;Data Analyses;Death Rate;Development;differential expression;Endothelial Cells;Epidermal Growth Factor;Epithelial ovarian cancer;exhaustion;FDA approved;Fibroblasts;first-in-human;Genes;Genetic Transcription;genomic profiling;Growth;Home;Human;humanized antibody;Hypoxia;Immune;Immune checkpoint inhibitor;Immune response;Immunosuppression;improved;in vivo;Infiltration;innovation;insight;Interferons;lead candidate;Macrophage;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Molecular;Monoclonal Antibodies;mouse model;novel;ovarian neoplasm;Ovarian Tissue;Paclitaxel;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;phase 1 study;Phase I Clinical Trials;Physiologic Neovascularization;Plasma;pre-clinical;recruit;Recurrence;Regulation;Reporting;Resistance;response;Role;Safety;Serous;Signal Pathway;Signal Transduction;single cell analysis;Source;T-Lymphocyte;targeted treatment;taxane;Testing;The Cancer Genome Atlas;Therapeutic;therapy outcome;Tissues;tumor;Tumor Angiogenesis;Tumor Burden;tumor growth;tumor microenvironment;tumorigenesis;TWIST1 gene;University of Texas M D Anderson Cancer Center;Vascular Endothelial Growth Factors;Work;wound healing

PROJECT_TITLE: Targeting EGFL6 in Ovarian Cancer


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Although multiple myeloma is the most common blood cancer in Black/African American individuals, Black/African American patients have been significantly underrepresented in multiple myeloma research studies and clinical trials. The proposed research is relevant to public health because it will identify important factors contributing to the health disparity in Black/African American patients with multiple myeloma by characterizing the genetic variations of the multiple myeloma tumor, its tumor microenvironment, and the impact of this variation on response to therapy and disease survival in a large, well-powered study of Black/African American patients with multiple myeloma. Since multiple myeloma has one of the most pronounced disparities in the incidence and mortality between Black/African American and European American patients, understanding variables that impact response to therapy among African Americans with multiple myeloma will be critical for identification of optimal therapeutic strategies in this underserved population.

PI_NAMEs: BAUGHN, LINDA B (contact)

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: Accounting;Affect;African American;African American population;African ancestry;Age;Age of Onset;American;Biological Factors;Biology;Black race;Cell Line;Clinic;Clinical Trials;cohort;Cytometry;Data;Disease;Disparity;drug sensitivity;Environmental Risk Factor;European;European ancestry;Frequencies;Functional disorder;Genetic;Genetic Drift;Genetic Risk;Genetic Variation;genome-wide;Genomics;Goals;health care availability;health difference;health disparity;Health Services Accessibility;Hematopoietic Neoplasms;Human;improved;Incidence;Individual;Malignant Neoplasms;Molecular Abnormality;mortality;Multiple Myeloma;Mutation;Newly Diagnosed;novel;Outcome;Patients;Pharmaceutical Preparations;Plasma Cells;predictive marker;prognostication;Prospective Studies;Public Health;Race;Regimen;Research;research study;response;Retrospective Studies;Risk;Selection for Treatments;Socioeconomic Factors;standard of care;T-Lymphocyte;Testing;Therapeutic;TP53 gene;transcriptome sequencing;transcriptomics;treatment response;tumor;Tumor Biology;tumor microenvironment;Underserved Population;Variant

PROJECT_TITLE: Differences in Tumor Biology of Multiple Myeloma in Association with African Ancestry


ADMINISTERING_IC: NS

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: TEMPE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: Neurodegenerative diseases progress over a long period of time before they become clinically apparent, and the physiological and molecular events which must ultimately be addressed to cure such diseases likely occur years before clinical diagnosis. The results from this data will provide the framework, and a potential therapeutic approach to identify one the earliest known factors in the progression of Parkinson’s disease, neuroinflammation.

PI_NAMEs: MASTROENI, DIEGO F (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, LUIS FLANAGAN

PROJECT_TERMS: Address;Affect;Anti-Inflammatory Agents;Antibodies;Antigens;Binding Proteins;Biological Markers;Blood Circulation;blood-brain barrier crossing;Brain;Brain Diseases;Brain region;Cell membrane;cell type;Cells;Central Nervous System;Cerebrospinal Fluid;Chemicals;Clinical;clinical diagnosis;Communication;comorbidity;Complement;cytokine;Data;density;design;Diagnosis;differential expression;Disease;Disease associated microglia;disorder risk;Encapsulated;Encephalitis;Etiology;Event;exosome;extracellular;extracellular vesicles;Family;fighting;Genes;glial activation;Human;human data;human induced pluripotent stem cells;Immune;immune stimulant;Individual;Infection;Inflammation;Inflammatory;Institution;Leukocytes;Life;liquid chromatography mass spectrometry;member;Membrane;Membrane Proteins;Messenger RNA;Meta-Analysis;Methods;Microglia;MicroRNAs;Molecular;Molecular Sieve Chromatography;monocyte;Mononuclear;Multivesicular Body;Nerve Degeneration;Neurobiology;Neurodegenerative Disorders;neuroinflammation;novel;Parents;Parkinson Disease;particle;Pathogenesis;Pathologic;Pathway interactions;Patients;Peripheral;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;Physiological;Physiological Processes;Play;protective effect;Publishing;response;RNA;Role;Sampling;Secure;Serum;Signaling Molecule;single nucleus RNA-sequencing;Stimulus;Substantia nigra structure;Testing;Therapeutic;Time;Tissues;TNF gene;tool;transcriptome sequencing;treatment strategy;vesicular release;Work

PROJECT_TITLE: Using Peripheral Microglial Exosomes to predict brain inflammation in the human Parkinson’s brain

STUDY_SECTION: CMBG

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


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: CHICAGO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative Potassium channels are membrane proteins that catalyze the transfer of K+ ions down an electrochemical gradient with high efficiency and selectivity. Understanding of voltage-dependent K+ channel structure and function relates directly to health and disease. Their function has been associated with such basic cellular functions as the regulation of electrical activity, signal transduction and osmotic balance. K+ channels are members of the voltage-dependent channel superfamily, which include explicitly voltage-activated channels (Na+, Ca2+, and a large number of K+ channels), as well as voltage-independent channels (i.e., the inward rectifiers and the cyclic nucleotide activated channels). The sub-family of non-domain swapped K+ channels include a great deal of functional diversity, including depolarization activated (EAG, hERG), hyperpolarization-activated (KAT1, HCN), and dual voltage and Ca2+ activation (BK). In higher organisms, dysfunctions associated to these channels may lead to uncontrolled periods of electrical hyperexcitability, like epileptic episodes and cardiac arrhythmias. Not surprisingly, voltage-dependent channels are also the target of many therapeutic agents.

PI_NAMEs: PEROZO, EDUARDO A (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Address;Aplysia;Arrhythmia;Attention;base;Binding;Biochemical;Biophysics;Cardiac;Cell Physiology;Characteristics;Charge;Ciona intestinalis;Communication;Complex;Computer Models;Computing Methodologies;Couples;Coupling;Cryoelectron Microscopy;Cyclic Nucleotides;Cytoplasm;Data;Derivation procedure;Disease;Electrophysiology (science);Electrostatics;Engineering;Enzymes;Epilepsy;Equilibrium;Event;Experimental Designs;experimental study;Face;Functional disorder;Goals;Health;Heterogeneity;Human;improved;insight;Ion Channel;Ion Channel Gating;Ions;large-conductance calcium-activated potassium channels;Lead;member;Membrane;Membrane Potentials;Membrane Proteins;Methanococcus;Modeling;Molecular;Molecular Conformation;Motion;Movement;Mutagenesis;mutant;Mutation;Myotonia;Nature;Organism;Osmosis;Phosphoric Monoester Hydrolases;Physiological;Physiology;Potassium Channel;Process;Property;Proteins;Protons;Regulation;Research;Resolution;response;Role;Scanning;Sea Anemones;sensor;Series;Signal Transduction;Site;Slide;Spin Labels;Structure;success;System;Techniques;Testing;Therapeutic Agents;Toxin;voltage;voltage clamp;X-Ray Crystallography

PROJECT_TITLE: Structural Basis of Coupling and Dynamics in K+ Channels


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

PHR: Project 4 PROJECT NARRATIVE The proposed research is relevant to public health because it aims to develop novel ovarian cancer therapeutic strategies with a durable therapeutic outcome to overcome PARP inhibitor resistance by targeting epigenetic regulator p300 using clinically applicable small molecule inhibitor IACS16559. Therefore, the proposed research is relevant to the part of the NIH’s mission that pertains to developing fundamental knowledge that will reduce the burden of human illness.

PI_NAMEs: ZHANG, RUGANG  (contact)

PROJECT_TERMS: Acidity;arm;biomarker identification;brca gene;BRCA mutations;cancer cell;Cancer Center;Cancer Model;Cancer Patient;Cell Line;Cells;Clinical;clinical application;clinical efficacy;Clinical Management;clinical predictors;Clinical Trials;CRISPR screen;Data;Dose;Double Strand Break Repair;efficacy evaluation;Eligibility Determination;EP300 gene;Epigenetic Process;Epithelial ovarian cancer;Exhibits;extracellular;FDA approved;Genes;genome-wide;Goals;homologous recombination;homologous recombination deficiency;Human;Impairment;improved;In Vitro;in vivo;inhibitor;innovation;insight;Intervention;Knowledge;Maintenance;Malignant neoplasm of ovary;Maximum Tolerated Dose;Methods;Mission;Mutate;Mutation;Nonhomologous DNA End Joining;Normal tissue morphology;novel;novel strategies;novel therapeutic intervention;Pathway interactions;patient derived xenograft model;Patients;Phase;Phase I Clinical Trials;phase I trial;Phosphorylation;Platinum;Poly(ADP-ribose) Polymerase Inhibitor;Poly(ADP-ribose) Polymerases;potential biomarker;Pre-Clinical Model;predicting response;predictive marker;Public Health;Recommendation;Recurrence;Research;Resistance;response;Safety;small molecule inhibitor;Specimen;synergism;Therapeutic;therapy outcome;Toxic effect;Transcription Coactivator;translational study;Translations;tumor;tumor microenvironment;United States National Institutes of Health;University of Texas M D Anderson Cancer Center;Up-Regulation

PROJECT_TITLE: Targeting p300 to Overcome PARP inhibitor resistance induced by acidic 				tumor microenvironment


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative Risk of Alzheimer’s Disease and Related Dementias (ADRD) accumulates throughout the life course and disproportionately burdens older Black and Hispanic/Latinx adults in the U.S. Understanding the role that adverse childhood experiences and neighborhood deprivation play in ADRD risk overall and within racial/ethnic subgroups may elucidate root causes of the disparities observed among older American adults and motivate tailored, culturally sensitive strategies and structural reform to reduce risk. This research proposal will develop and link measures to a large diverse longitudinal aging cohort and apply a life course perspective from childhood to midlife to older age to better understand social and structural determinants of health and cognitive outcomes in U.S. adults and within racial/ethnic groups.

PI_NAMEs: LEE, ADRIENNE R.S. (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: accelerated epigenetic aging;Address;Adult;adverse childhood events;Affect;Aging;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Area;Black race;Buffers;Censuses;Childhood;childhood adversity;Cognitive;Cognitive aging;cognitive function;cohort;Communities;Complex;Data;Dementia;dementia risk;deprivation;design;Disparity;Early identification;Environment;Environmental Risk Factor;Equity;ethnic difference;Ethnic Origin;Ethnic Population;experience;Factor Analysis;Family;Family Study;hallmarks of aging;Health;Health and Retirement Study;Health behavior and outcomes;health equity;health inequalities;healthspan;Heterogeneity;Hispanic;human old age (65+);improved;indexing;Individual;insight;Institution;International;Intervention;late life;Latino;Latinx;Life;Life Cycle Stages;Link;Literature;Measures;Mediation;middle age;National Institute on Aging;Neighborhoods;novel;older adult;Outcome;Paper;Pathway interactions;Phase;Physical Function;Play;Policies;Population;Postdoctoral Fellow;prevent;Prevention strategy;protective factors;Psychometrics;Race;racial difference;racial population;Research;Research Project Grants;Research Proposals;Residential Mobility;resilience factor;Retirement;Risk;risk mitigation;Risk Reduction;Role;Sampling Studies;social;social determinants;Socioeconomic Status;stressor;structural health determinants;Surveys;United States;Universities;vulnerable community;Wisconsin;Work

PROJECT_TITLE: Associations of Adverse Childhood Experiences with Midlife Neighborhood Deprivation and Cognitive Trajectories and Dementia Outcomes in Later Life


ED_INST_TYPE: HOSPITALS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: PROJECT NARRATIVE Analysis of SPOP mutant (SPOPmut) and SPOP wild-type castration-resistant prostate cancer (CRPC) clinical data sets revealed a 29-gene “SPOPmut gene signature,” which experimentally reflected intrinsic epithelial non- canonical STING-NF-κB and paracrine-mediated macrophage signaling activities driving tumor cell growth and survival in SPOPmut CRPC. We also showed that PARP inhibitor (PARPi) treatment of SPOPmut CRPC cells markedly induces DNA damage, activates canonical cGAS-STING-TBK-IFN-ß signaling, and suppresses non- canonical STING-NF-κB-IL-6/STAT3, in part through inhibitory phosphorylation (S754-STAT3), leading to growth suppression and apoptotic signaling. Our proposed, paradigm-shifting studies will define the underlying mechanisms and clinical markers in prostate cancer models and tissue samples from PARPi-based clinical trials to understand how PARPi influences innate and adaptive immune signaling in the context of SPOPmut prostate cancer and potentially other genetic mutations (e.g., CHD1 deletions) that reflect the SPOPmut phenotype.

PI_NAMEs: THOMPSON, TIMOTHY CHARLES (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: Aftercare;androgen independent prostate cancer;Androgens;Apoptotic;Automobile Driving;Binding Proteins;Biological Markers;Blood specimen;Castrate sensitive prostate cancer;Castration;cell growth;Cell model;Cell Survival;Cells;CHD1 gene;chromatin protein;Chromatin Remodeling Factor;Clinical;Clinical Data;Clinical Markers;Clinical Trials;Coculture Techniques;Combined Modality Therapy;Consensus;Cullin Proteins;cytokine;Data Set;DNA analysis;DNA Damage;DNA Sequence Alteration;Epithelium;Equilibrium;Evaluation;experimental study;Genes;Genetic;genetic signature;Growth;Heterozygote;High Mobility Group Proteins;Human;Immune signaling;in vivo;Interferon-beta;Interleukin-6;Macrophage;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Methods;Missense Mutation;Modeling;Mus;mutant;Mutation;neoplastic cell;neutralizing antibody;Other Genetics;paracrine;Pathway interactions;patient biomarkers;patient subsets;Patients;Phenotype;Phosphorylation;Poly(ADP-ribose) Polymerase Inhibitor;prostate cancer cell;prostate cancer model;Proteins;Proteomics;recruit;Regulation;Resistance;resistance mechanism;response;Role;Sampling;Signal Transduction;stable isotope;STAT3 gene;Stat3 protein;Stimulator of Interferon Genes;T-Lymphocyte;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic Effect;therapeutic evaluation;Tissue Sample;Treatment Efficacy;tumor;tumor growth;tumor microenvironment;Tumor Suppressor Genes;ubiquitin ligase;Up-Regulation

PROJECT_TITLE: Targeting Non-Canonical STING Signaling to Treat SPOP Mutant Castration-Resistant Prostate Cancer

STUDY_SECTION: ATA

STUDY_SECTION_NAME:
Advancing Therapeutics A Study Section
[ATA]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: NEW YORK

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE The vast majority of transcripts within the cell consist of non-coding RNAs, which can modulate almost every molecular process. Viruses, unsurprisingly, also produce their own non-coding RNAs that can hijack host machineries to regulate both viral and host pathways. We will study the still highly elusive viral non-coding RNA biology, understanding of which will ultimately lead to new treatment options for human diseases.

PI_NAMEs: PAWLICA, PAULINA  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: 2019-nCoV;Acute;Anti-viral Response;Biology;Cell Nucleus;Cell Physiology;cell transformation;Cells;Coronavirus;COVID-19;current pandemic;Cytoplasm;Data;Development;DNA Viruses;flexibility;Funding;Gene Expression;Genes;Genome;Herpesviridae;Human;human disease;insight;interdisciplinary approach;Interferons;Knowledge;Mediating;Messenger RNA;MicroRNAs;Molecular;Names;novel;novel strategies;Nuclear;Oncogenic;Pathway interactions;posttranscriptional;Process;programs;Proteins;Research;Respiratory Disease;RNA;RNA Splicing;RNA Viruses;RNA, Messenger, Splicing;RNA-Binding Proteins;Role;Saimiriine Herpesvirus 2;SARS-CoV-2 pathogenesis;Signal Transduction;Small Nuclear RNA;Small RNA;Source;Transcript;Translations;tumorigenesis;Untranslated RNA;Viral;Viral Genes;Virion;virology;Virus;Virus Diseases;Virus Latency;virus related cancer

PROJECT_TITLE: Small RNA-mediated warfare between viruses and their hosts

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Ovarian Cancer;Rare Diseases;Women's Health Research

PI_NAMEs: YUAN, YING  (contact)

PROJECT_TERMS: Animals;archive data;Basic Science;Bioinformatics;Biometry;Biostatistics Core;career;Clinical Sciences;Clinical Trials;computerized data processing;Data;data acquisition;Data Analyses;Data Analytics;data handling;data management;Data Set;Databases;design;Development;Ensure;experience;experimental study;Genomics;Goals;high throughput screening;innovation;Lateral;Logistics;Malignant neoplasm of ovary;member;Methodology;Methods;Paper;programs;Publications;Publishing;Reproducibility;Research;Research Design;Research Personnel;Research Project Grants;Resources;Statistical Data Interpretation;statistics;success;Translational Research;University of Texas M D Anderson Cancer Center;Work

PROJECT_TITLE: Bioinformatics and Biostatistics Core


ED_INST_TYPE: UNIVERSITY-WIDE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: Project Narrative Innovative method development to synthesize nitrogen-containing molecules are of importance due to the high presence of nitrogen in pharmaceutical drug candidates. Methods to use reactive early transition metal metallazirdine offers a transformative approach in the preparation of selectively substituted amines and N- heterocycles due to its high atom economy and tunable catalyst and reaction conditions. New methodology and catalysis reactions control selectivity, achieve high reactivity, and expand on the amine substrate scope that can be further functionalized towards the synthesis of pharmaceutical drug candidates.

PI_NAMEs: VANG, ZOUA PA  (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TITLE: Ti-catalyzed cascading hydroaminoalkylation as a route to complex functionalized amines


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Networking and Information Technology R&D (NITRD)

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: PROJECT NARRATIVE The Biological Magnetic Resonance Data Bank (BMRB) data repository supports the biomedical research efforts of the world wide biomolecular magnetic resonance (MR) community. Magnetic resonance spectroscopy is a key tool used to understand the biomedical significance of protein and nucleic acid structures, to identify potential drug therapeutics, and to characterize metabolites and disease biomarkers.

PI_NAMEs: HOCH, JEFFREY C (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TERMS: Advisory Committees;archived data;Archives;Binding;Bioinformatics;Biological;Biological Markers;biological systems;biomacromolecule;Biomedical Research;Biomolecular Nuclear Magnetic Resonance;Biophysics;Certification;chemical property;Chemicals;Collaborations;collaboratory;Collection;Communities;community engagement;Community Outreach;Complex Mixtures;Computer software;computerized data processing;cyber security;Data;Data Analyses;data archive;Data Collection;data repository;data resource;data standards;data submission;Databases;Dependence;Deposition;Disease;drug discovery;Educational workshop;Electron Microscopy;Ensure;Europe;experience;federated data;Feedback;Fostering;Hybrids;Individual;Information Systems;Infrastructure;insight;International;Japan;Journals;Link;macromolecule;Magnetic Resonance;Magnetic Resonance Spectroscopy;Maintenance;member;metabolomics;Metadata;Molecular;Molecular Conformation;molecular dynamics;molecular modeling;Molecular Structure;Monitor;Names;Natural Products;NMR Spectroscopy;novel strategies;Nuclear Magnetic Resonance;nucleic acid structure;Nucleic Acids;operation;peer;Pharmaceutical Preparations;Population;Posture;Productivity;protein data bank;Protein Dynamics;protein structure;Proteins;Recommendation;Relaxation;repository;Research;Research Personnel;Resources;Retrieval;Role;Sampling;screening;Secure;Services;small molecule;software development;Software Tools;solid state nuclear magnetic resonance;structural biology;structural genomics;Structure;symposium;System;Technology;Text;Therapeutic;three dimensional structure;Time;tool;Universities;Validation;web server;web site;working group

PROJECT_TITLE: Biological Magnetic Resonance Data Bank


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Digestive Diseases - (Gallbladder);Genetics;Human Genome;Immunotherapy;Liver Cancer;Liver Disease;Rare Diseases

ORG_DEPT: PHARMACOLOGY

PHR: Project Narrative Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary liver cancer with a poor response to immune checkpoint inhibitors (ICI), which has not been improved due to poor understanding of the immunosuppressive mechanisms associated with ICC progression. We have developed a novel mouse model of ICC that shows human-like stepwise progression accompanied by desmoplasia and CD8+ T cell exclusion. This model is ideally suited for studying the immunobiology of ICC and finding new ways to improve the efficacy of existing ICI-based therapies for this malignancy.

PI_NAMEs: KARIN, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: NADEAU, CHRISTINE FRANCES

PROJECT_TERMS: Accounting;Alcohol abuse;Biliary;biliary tract;cancer cell;cancer type;CD8-Positive T-Lymphocytes;Cell Communication;Cell Surface Receptors;Cells;Characteristics;checkpoint inhibition;cholangiocyte;Cholestasis;Clinical;Clinical Management;Complication;Data;Desmoplastic;Diagnosis;Differential Diagnosis;Early Diagnosis;endoplasmic reticulum stress;Epigenetic Process;Evaluation;Evolution;Exclusion;Exhibits;experimental study;Failure;Fibroblasts;Goals;Hepatobiliary;Hepatocyte;High Fat Diet;Human;Immune;Immune checkpoint inhibitor;Immunobiology;Immunocompetent;immunogenic;Immunophenotyping;Immunosuppression;Immunotherapy;improved;Incidence;Inflammatory Bowel Diseases;information gathering;inhibitor;Intraepithelial Neoplasia;Intrahepatic Cholangiocarcinoma;KDR gene;Lesion;Malignant - descriptor;Malignant Neoplasms;Maps;Mediating;Modeling;Molecular;mouse model;Mus;Mutation;Myeloid-derived suppressor cells;neoplastic;Nodule;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;Oncogenic;overexpression;Pathogenesis;Pathologic;pressure;prevent;Primary carcinoma of the liver cells;Primary Malignant Neoplasm of Liver;progenitor;Radiology Specialty;Reaction;regenerative;response;Risk Factors;Signal Transduction;single nucleus RNA-sequencing;Study models;Survival Rate;T cell receptor repertoire sequencing;T-cell receptor repertoire;T-Lymphocyte;Techniques;Therapeutic;tobacco abuse;transcription factor;Transcriptional Activation;transcriptome sequencing;transcriptomics;Translating;tumor;tumor microenvironment;tumor-immune system interactions;Tumor-Infiltrating Lymphocytes;Variant;Vegf Inhibitor

PROJECT_TITLE: A new mouse model for studying the pathogenesis and immunobiology of intrahepatic cholangiocarcinoma and improving its immunotherapy

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


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

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative Oligodendrocyte precursor cells (OPCs) give rise to oligodendrocytes, the myelinating cells of the central nervous system. In the past they have mostly been thought of as simple progenitor cells, but recent studies have shown that they can surveil their environment and respond to injury, and I have observed that these OPCs take on a unique shape and density in two areas where neurons are continuously remodeling in the adult mouse: the hippocampus and the olfactory bulb. The goal of this project is to test the hypothesis that OPCs facilitate the integration of newborn neurons in these regions of the adult brain, and this novel understanding OPC regulation of neuronal circuits could give us insight into neuronal plasticity in development and disease.

PI_NAMEs: KIM, ANYA  (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: Ablation;Address;Adopted;Adult;Affect;Aging;aging population;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Antigen Presentation;Area;Atrophic;Automobile Driving;Axon;Behavior;Brain;Brain Diseases;Cell Separation;cell type;Cells;Central Nervous System;Central Nervous System Diseases;Cicatrix;Complex;Coupled;CSPG4 gene;density;dentate gyrus;Deposition;Development;Disease;Disease Progression;Elderly;Environment;Exercise;Exhibits;experience;Extracellular Matrix;fluorophore;Gene Expression Profile;genetic manipulation;Genetic Transcription;Goals;granule cell;hippocampal atrophy;Hippocampus;human old age (65+);Image;Impairment;in vivo;in vivo imaging;Individual;Inflammation;Injury;insight;Knowledge;Label;Learning;Life;Maintenance;Major Histocompatibility Complex;Membrane;Memory;Memory Loss;Metabolic;Microglia;Molecular Analysis;Molecular Profiling;Morphology;Motivation;mouse model;Mus;Nerve Degeneration;neural circuit;Neurodegenerative Disorders;neurogenesis;Neuroglia;neuron component;neuron loss;neuronal circuitry;Neuronal Plasticity;neuronal survival;Neurons;Newborn Infant;newborn neuron;novel;old mice;olfactory bulb;oligodendrocyte progenitor;Oligodendroglia;Pathogenesis;Pathologic;Persons;Phenotype;Play;Population;precursor cell;Process;Production;Regulation;repaired;Reporter;restoration;Role;Shapes;single-cell RNA sequencing;Site;stem cells;Stratum Lucidum;Stream;Synapses;synaptic pruning;Testing;Viral;Visualization

PROJECT_TITLE: The role of oligodendrocyte precursor cells in circuit remodeling in the mature brain


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

PI_NAMEs: LIU, JINSONG  (contact)

PROJECT_TERMS: Archives;Ascites;Award;Benign;biomarker identification;Biopsy Specimen;Cancer Center;career;Clinical;Clinical Data;Code;Colon;Confidentiality of Patient Information;Consult;Cyst;data access;Databases;Development;Diagnosis;Drug resistance;endometriosis;Endometrium;Evaluation;experience;Experimental Designs;experimental study;Feasibility Studies;Female Genital Neoplasms;Formalin;Freezing;Frozen Sections;Funding;Generations;Goals;Gynecologic;Human;Immunohistochemistry;In Situ Hybridization;Individual;Institution;Internet;Intranet;Laboratories;Laboratory Research;Link;Malignant neoplasm of ovary;Mammalian Oviducts;Microscopic;Modeling;Mucous Membrane;Mus;Normal tissue morphology;novel therapeutics;Organoids;Ovarian;Ovarian Diseases;Ovary;Paraffin Embedding;Pathologic;Pathologist;Pathology;patient derived xenograft model;Patients;Population Research;Process;quality assurance;Research;Research Personnel;Research Project Grants;Research Proposals;Resources;Sampling;Security;Services;Slide;Solid Neoplasm;Source;Specimen;Technology;Testing;Tissue Banks;Tissue Embedding;Tissue Microarray;Tissues;tumor;Tumor Bank;Tumor Tissue;University of Texas M D Anderson Cancer Center;virtual

PROJECT_TITLE: Pathology Core


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative Ligand binding is fundamental to biology but technologies to explore proteome-wide protein engagement are limited. The work proposed here will build a cornerstone mass-spectrometry-based proteomic technology suite to reveal proteome-wide protein-ligand interactions. Here we demonstrate the development and implementation in a focused way on a small library of small-molecule drugs to highlight the potential of this technology to bring robust quantitative approaches to study ligand binding at scale.

PI_NAMEs: SCHWEPPE, DEVIN KARL (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Address;Binding;Biological Assay;Biological Process;Biology;Cells;Code;Complex;Data;data acquisition;Dependence;Development;Dose;Experimental Designs;experimental study;Gene Expression Profile;Genes;Genomics;Human;Knock-out;Libraries;Ligand Binding;Ligands;Lipids;Mass Spectrum Analysis;Measures;Metals;Methods;Pharmaceutical Preparations;Proteins;Proteome;Proteomics;Research;response;Sampling;small molecule;small molecule libraries;technological innovation;Technology;Time;Translational Research;Work

PROJECT_TITLE: Technology for evaluating drug-binding responses to small-molecule perturbation


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Genetics;Neurofibromatosis;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative Microphthalmia (small eye), anophthalmia (absence of eye) and coloboma (defect in closure of the optic fissure) are severe congenital ocular birth defects that can cause up to 25% of childhood blindness worldwide. Thus, for understanding the cause of these birth defects and develop therapeutic strategies, knowledge of the mechanisms regulating eye development is essential. The goal of the proposed research is to define the role of the molecular motor Myo10 and to investigate the function of Hippo signaling and Yap/Taz in retinal pigment epithelium development and during early ocular morphogenesis.

PI_NAMEs: FUHRMANN, SABINE  (contact)

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: Actins;Anophthalmos;Binding;Blindness;Candidate Disease Gene;Cell Line;Childhood;Coloboma;Complex;Congenital Abnormality;Cytoskeleton;Data;Defect;Development;Embryo;Embryonic Development;Enhancers;Ensure;Equilibrium;Essential Genes;Event;Exhibits;experimental study;Eye;Eye Development;Eye diseases;Filopodia;Funding;gene regulatory network;Genes;Goals;Growth;Homeostasis;Human;Image;In Vitro;Individual;Knowledge;Maintenance;malformation;Mesenchyme;Microphthalmos;Molecular;Molecular Motors;Morphogenesis;Motor;Mutant Strains Mice;Mutation;Myosin ATPase;neuroepithelium;Neurofibromin 2;novel;Nuclear Translocation;optic cup;Optic vesicle;Optics;Organ Size;Pathway interactions;Process;Production;Proliferating;regenerative;Regulation;Regulatory Pathway;Research;Resolution;rho GTP-Binding Proteins;Role;Severities;Signal Pathway;Signal Transduction;stem cell division;Structure of retinal pigment epithelium;Tertiary Protein Structure;Therapeutic;tissue regeneration;Tissues;Transcriptional Regulation;tumor;Tumor Suppressor Genes

PROJECT_TITLE: Regulation of Eye Morphogenesis

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Ovarian Cancer;Prevention;Rare Diseases;Women's Health Research

PI_NAMEs: BAST, ROBERT C (contact)

PROJECT_TERMS: Address;Ally;anti-cancer research;Area;Award;Basic Science;Budgets;Cancer Center;candidate identification;Clinical;Clinical Investigator;Clinical Research;Collaborations;Data;Dedications;Department of Defense;design;Development;Discipline;Disease;Early Diagnosis;Early treatment;Financial Support;Foundations;Funding;Funding Mechanisms;Future;Goals;Human;improved;Incidence;innovation;Institution;Malignant neoplasm of ovary;Malignant Neoplasms;Manuscripts;Medical center;mortality;novel;Ovarian;ovarian cancer prevention;patient population;peer;Peer Review;Population Research;Prevention;Productivity;Program Research Project Grants;programs;Publishing;Quality of life;Research;Research Personnel;Research Project Grants;Resources;Rest;Scientist;Specimen;supportive environment;Texas;translational potential;Translational Research;translational study;University of Texas M D Anderson Cancer Center;Woman;Work

PROJECT_TITLE: Developmental Research Program


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Immunization;Infectious Diseases

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Narrative Viral transmembrane spike glycoproteins binding to human receptors mediate the entry of SARS-CoV-2 to the host cell, which causes COVID-19. Despite their functional importance, the real-time structural and functional dynamics of spike proteins and their interactions with the other function-regulated biomolecules on host cells are still unknown. We will use state-of-the-art high-speed atomic force microscopy (HS-AFM) to directly visualize the real-time structural dynamics and intermolecular interactions in the spike protein system, which is critical for understanding the molecular mechanism of receptor-mediated virus entry.

PI_NAMEs: LIN, YI-CHIH  (contact)

PROJECT_TERMS: 2019-nCoV;ACE2;Architecture;Atomic Force Microscopy;Binding;Biochemical;Biological;Biological Assay;Biophysics;Cell membrane;Cell surface;Cells;COVID-19;COVID-19 therapeutics;Crystallography;Diagnostic;Electrons;Environment;Enzymes;Event;experimental study;Fluorescence Microscopy;Glycoproteins;Human;Imaging Techniques;Integral Membrane Protein;intermolecular interaction;Knowledge;Mammalian Cell;Mediating;Membrane;Membrane Fusion;Methods;Microscopic;Molecular;molecular assembly/self assembly;Molecular Conformation;Nature;neutralizing monoclonal antibodies;novel;Peptide Hydrolases;Physiological;Play;Preventive;Process;Proteins;receptor;reconstitution;Role;SARS-CoV-2 spike protein;Speed;structural imaging;Structure;System;Techniques;Therapeutic;Time;Viral;Viral Genome;Virus;virus envelope;Visualization

PROJECT_TITLE: Real-time structural and functional studies of SARS-CoV-2 spike proteins


ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: OVERALL PROJECT NARRATIVE Glioblastoma (GBM) remains a fatal brain cancer with little progress in therapy. We aim to improve immunotherapy against this cancer by exploiting the capacity of oncolytic viruses (OVs) to rapidly change the microenvironment of the tumor from one that is profoundly immunosuppressive to one that is more immune- activated. We have generated novel OVs and have tested one in a first in human clinical trial over the last funding cycle. Data from this trial is now informing the next steps in improving OV immunotherapy: we propose clinical trial scientific correlate analyses that will lead to improved versions of OVs for clinical trials, subscribing to the concept from the “lab bench to the clinic and back to the lab bench”. The ultimate impact from our findings will result in improved patient survival outcomes.

PI_NAMEs: CHIOCCA, E. ANTONIO (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: Adenosine;Antibodies;arm;Back;bench to bedside;biobank;Bioinformatics;Biological;Biometry;CD47 gene;checkpoint inhibition;chemokine;Cities;Clinic;Clinical;Clinical Data;clinical translation;Clinical Trials;Dana-Farber Cancer Institute;Data;design;Eating;Effectiveness;efficacious treatment;Engineering;experience;first-in-human;Funding;Genes;Glioblastoma;Herpesvirus 1;Hospitals;Human;human subject;Immune;Immune system;Immunologic Stimulation;Immunologics;Immunosuppression;Immunotherapy;improved;In Situ;insight;Learning;Macrophage;Malignant Glioma;Malignant neoplasm of brain;Malignant Neoplasms;Medical;Medical center;medical schools;Molecular;Myeloid Cells;neoplastic cell;next generation;notch protein;novel;Ohio;oncolytic herpes simplex virus;Oncolytic Immunotherapy;oncolytic virotherapy;Oncolytic viruses;palliative;Pathway interactions;Patients;peripheral blood;Phase I Clinical Trials;phase I trial;Pre-Clinical Model;Preclinical Testing;Prediction of Response to Therapy;Principal Investigator;Production;proteomic signature;RANTES;Recurrence;Research;Resistance;response;service utilization;Signal Transduction;Solid Neoplasm;standard of care;success;survival outcome;Testing;Therapeutic;timeline;transcriptomics;Translating;tumor;tumor microenvironment;Universities;Vertebral column;Woman

PROJECT_TITLE: Circumventing Barriers to Effective Oncolytic Virotherapy of Malignant Gliomas


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Brain Disorders;Neurosciences;Substance Misuse

ORG_CITY: CHAPEL HILL

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative Alcohol use disorder (AUD) is a national health crisis; understanding how alcohol use causes changes in brain activity is paramount to developing more effective treatments for AUD. The bed nucleus of the stria terminalis (BNST) is a brain region which has been highly implicated in regulating alcohol consumption and relapse, but the mechanisms by which this occurs remain unclear. The experiments outlined in this proposal seek to elucidate how chronic alcohol exposure disrupts tonic and synaptic excitatory signaling in the BNST.

PI_NAMEs: CONLEY, SARA YI-LING (contact)

PROGRAM_OFFICER_NAME: LIU, QI-YING

PROJECT_TERMS: Acute;addiction;Affect;Affective Symptoms;Alcohol consumption;alcohol effect;alcohol exposure;alcohol relapse;alcohol seeking behavior;alcohol use disorder;Alcohols;AMPA Receptors;Anterolateral;Anxiety;Area;Attenuated;Brain;Brain region;Calcium;Cell Nucleus;Cells;Chronic;clinical development;clinically relevant;Coupled;Data;Dimensions;Dorsal;effective therapy;Electrophysiology (science);Ethanol;Event;Excitatory Postsynaptic Potentials;experimental study;Exposure to;Family;Female;Fluorescent in Situ Hybridization;Functional disorder;Genetic;genome wide association study;Genotype;Glutamate Receptor;glutamatergic signaling;Glutamates;Goals;Health;Image;In Situ Hybridization;in vivo calcium imaging;insight;interest;Knock-out;Knockout Mice;Knowledge;Ligands;Link;Long-Term Depression;Macaca;Macaca mulatta;male;Mediating;Messenger RNA;Modeling;mouse model;mRNA Expression;Mus;negative affect;Neuronal Dysfunction;neuronal excitability;Neurons;neuroregulation;nonhuman primate;novel;patch clamp;Pattern;Permeability;Pharmaceutical Preparations;Phenotype;Population;Prosencephalon;receptor;Reporting;Research;response;Role;Self Administration;sex;Sex Differences;Signal Transduction;species difference;Stress;Structure of terminal stria nuclei of preoptic region;Synapses;Synaptic plasticity;System;targeted treatment;Testing;transmission process;vapor;Withdrawal;Work

PROJECT_TITLE: Investigating tonic and synaptic excitatory signaling in the bed nucleus of the stria terminalis across models of alcohol exposure


PROJECT_TERMS: American Association of Cancer Research;American Society of Clinical Oncology;anti-cancer research;Area;Award;Basic Science;bench to bedside;Budgets;Cancer Biology;cancer diagnosis;Cancer Research Project;career;career development;Clinical;clinical care;Clinical Research;Collaborations;Dedications;design;Development;Development Plans;Diagnosis;Disease;Early Diagnosis;Early treatment;Education;Ensure;experience;Faculty;Fostering;Foundations;Funding;Goals;Grant;Healthcare;improved;innovation;Institution;International;Intervention;Investigation;Laboratories;Leadership;Malignant neoplasm of ovary;meetings;member;Mentors;Mentorship;Minority;Morbidity - disease rate;mortality;National Center for Advancing Translational Sciences;next generation;novel;Ovarian;Paper;Patients;Peer Review;Postdoctoral Fellow;Prevention;programs;Publishing;recruit;Research;Research Personnel;Resources;Scientist;supportive environment;symposium;Training;Translating;translational approach;Translational Research;United States National Institutes of Health;University of Texas M D Anderson Cancer Center;Woman;Work;Writing

PROJECT_TITLE: Career Enhancement Program


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Gene Therapy;Genetics;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE – PROJECT 1 Glioblastoma (GBM) is a lethal form of brain cancer that affects approximately 10,000 Americans annually. Oncolytic viruses (OV) are a promising therapeutic option for GBM patients; however, durable treatment will require both vigorous viral oncolytic activity and awakening of anti-tumor immunity. We propose to enhance the anti-cancer efficacy of an existing oHSV platform (Project 2) through vector modifications intended to improve viral oncolysis and by arming the virus with genes that support the induction of anti-tumor immunity.

PI_NAMEs: GLORIOSO, JOSEPH C (contact)

PROJECT_TERMS: adaptive immune response;Adenosine;adenosine deaminase;Affect;Aggressive behavior;American;Animals;anti-cancer;Antigen-Presenting Cells;Antitumor Response;Area;arm;Biological Assay;CD8-Positive T-Lymphocytes;Cell Death;cell killing;Cell Line;Cell Separation;Cells;Characteristics;Clinic;clinical development;Clinical Trials;Clonal Expansion;Collaborations;combinatorial;Data;design;Development;Dissociation;effective therapy;effector T cell;efficacy evaluation;efficacy study;Engineering;Evaluation;exhaust;Exhibits;Genes;Glioblastoma;Glycoproteins;Goals;Growth;Heterogeneity;HSV vector;Human;Immune;Immune checkpoint inhibitor;immunogenic;Immunosuppression;improved;In Vitro;in vitro activity;in vivo;in vivo evaluation;Infiltration;Inflammatory;insight;Interleukin-12;Ligands;Macrophage;Malignant Glioma;Malignant neoplasm of brain;Mediating;Metabolic;Modeling;Modification;Monitor;mouse model;Mus;mutant;Mutation;Myeloid Cells;Myeloid-derived suppressor cells;Nature;neoplastic cell;novel;oncolysis;Oncolytic;oncolytic herpes simplex virus;oncolytic virotherapy;Oncolytic viruses;Outcome;Pathway interactions;patient derived xenograft model;patient response;Patients;PD-1 inhibitors;Performance;Phenotype;Population;pre-clinical;prevent;Production;programmed cell death protein 1;Proteins;PTEN gene;PVRL1;Receptor Cell;recruit;Recruitment Activity;Recurrence;Resistance;response;Safety;Simplexvirus;single-cell RNA sequencing;T cell response;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Time;Transgenes;Translating;Treatment Efficacy;tumor;Tumor Antigens;Tumor Cell Line;Tumor Immunity;tumor microenvironment;Variant;vector;Vertebral column;Viral;Viral Antigens;Viral Genes;Viral Load result;Virus;Virus Replication

PROJECT_TITLE: Project 1: Treatment of GBM using an oncolytic HSV engineered to improve immunogenic tumor destruction


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB

PHR: Project Narrative This project will create a new algorithmic framework combining model-based and data-driven approaches to accelerate the analysis of and enable high-resolution reconstructions from cellular cryo-electron and X-ray tomography data. Our algorithms will be validated on both simulated data with a varying degree of complexity as well as publicly available and published experimental datasets to assess the improvements provided by our approach over currently available analysis methods. To facilitate the dissemination and broad use of our computational tools, we will develop an open-source automated and user-friendly software that will streamline data analysis and negate the need for manual intervention, thereby making the technique accessible to a wider structural biology community.

PI_NAMEs: PANDE, KANUPRIYA  (contact)

PROJECT_TERMS: 3-Dimensional;Acceleration;Address;Algorithms;Biological;Cell Volumes;Cells;Communities;Complex;complex data;Computer software;computerized tools;Crowding;Cryoelectron Microscopy;Data;Data Analyses;Data Set;deep neural network;Electrons;Environment;experience;Frequencies;Goals;Heterogeneity;Hybrids;Image;Imaging Techniques;improved;In Situ;Intervention;Joints;Machine Learning;macromolecule;Manuals;mathematical model;Mechanics;Methods;Modeling;Molecular Conformation;Morphologic artifacts;Motion;nanometer;neglect;Noise;novel strategies;open source;Optics;Organelles;particle;Publishing;radiation effect;Radiation induced damage;reconstruction;Resolution;Roentgen Rays;Sampling;Series;Shapes;Signal Transduction;structural biology;Structure;Structure-Activity Relationship;Techniques;tomography;user friendly software;Visualization;X-Ray Crystallography;X-Ray Tomography

PROJECT_TITLE: Hybrid Model-Based and Data-Driven Frameworks for High-Resolution Tomographic Imaging


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE – PROJECT 2 We are pursuing detailed immunologic, biologic, and imaging analyses on human GBMs that were treated in a phase 1 clinical trial with a novel oncolytic virus (OV). We find that this form of immunotherapy induces a rapid T cell response characterized by infiltration of treated GBMs with CD8+, CD4+ T cells and B cells. Both the abundance of transcripts related to T cell and B cell infiltrates and the imaging changes observed correlate with patient responses. Proposed further analyses of tumors and peripheral blood will characterize changes associated with a response as well as characterize the tumor and viral antigens that these immune cells respond to. These studies are needed to fully understand the results of this completed trial in order to inform avenues to improve GBM immunotherapy.

PROJECT_TERMS: Adenosine;antigen binding;Antigen Presentation;Antitumor Response;B-Cell Antigen Receptor;B-Lymphocytes;Biological;Biological Markers;Biopsy Specimen;Blood;cancer infiltrating T cells;CD4 Positive T Lymphocytes;CD8B1 gene;Cells;chemokine;Clinical;Clinical Trials;cytokine;cytotoxic;Data;Development;Down-Regulation;Failure;FDA approved;Funding;Future;Glioblastoma;Glioma;Growth;Herpes Simplex Infections;HLA Antigens;Human;human subject;Image;imaging biomarker;Immune;immune cell infiltrate;immune checkpoint blockade;Immune response;Immunologics;Immunosuppression;Immunotherapy;immunotherapy trials;improved;In Situ;Infection;Infiltration;Japan;Magnetic Resonance Imaging;Malignant Glioma;Malignant Neoplasms;Measures;Mediating;Medical;Melanoma;Modeling;Molecular;Mus;Myeloid-derived suppressor cells;novel;Oncolytic;oncolytic herpes simplex virus;oncolytic virotherapy;Oncolytic viruses;patient response;Patient-Focused Outcomes;Patients;peripheral blood;Phase I Clinical Trials;phase I trial;Plasma;Population;potential biomarker;pre-clinical;Pre-Clinical Model;programs;Proteome;Publishing;rate of change;Recurrence;response;Serum;Simplexvirus;Specimen;Stimulus;success;T cell response;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;Therapeutic;Transcript;tumor;Tumor Antigens;tumor microenvironment;Tumor Virus Infections;tumor-immune system interactions;Tumor-Infiltrating Lymphocytes;Viral Antigens;Virus Diseases;Work;Xenograft procedure

PROJECT_TITLE: Project 2: Analyses of the human GBM microenvironment form clinical trial specimens treated with the oncolytic HSV, rQNestin34v.2


NIH_SPENDING_CATS: Aging;Sarcopenia

ORG_CITY: SYRACUSE

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

PHR: Although the relationship between mitochondrial dysfunction and muscle atrophy has been well- established, previous studies have mainly been focused on defects in oxidative phosphorylation (OXPHOS) as the cause of muscle atrophy. This application proposes to use a unique mouse model of mitochondrial dysfunction to investigate an OXPHOS-independent mechanism of muscle loss. The data may help in developing new therapies for treating muscle wasting in mitochondrial disease and potentially in aging.

PI_NAMEs: BRENNAN, NICHOLAS  (contact)

PROGRAM_OFFICER_NAME: BOYCE, AMANDA T

PROJECT_TERMS: Ablation;Acute;Adenine Nucleotide Translocase;Affect;aged;Aging;Amino Acids;Apoptosis;Attenuated;Autophagocytosis;Biochemical;Bioenergetics;biological adaptation to stress;Biological Assay;Cell Death;Cell Death Induction;Cessation of life;Chronic;Clinical;Cytosol;Data;Defect;Disease;Dual-Energy X-Ray Absorptiometry;Equilibrium;Fellowship;Goals;Histologic;in vivo;Inner mitochondrial membrane;insight;Knowledge;Mass Spectrum Analysis;Measurement;Mediating;Membrane Proteins;Mitochondria;Mitochondrial Diseases;mitochondrial dysfunction;Mitochondrial Proteins;Molecular;Morbidity - disease rate;mortality;mouse model;multicatalytic endopeptidase complex;Mus;Muscle;muscle aging;muscle form;muscle stress;Muscular Atrophy;Myopathy;NADH;normal aging;novel;novel therapeutics;overexpression;Oxidation-Reduction;Oxidative Phosphorylation;Oxidative Stress;Pathway interactions;Patients;Peptide Hydrolases;Phosphorylation;Phosphotransferases;Play;preservation;Process;Production;Protein Biosynthesis;protein degradation;Protein Import;Proteins;proteostasis;Quality of life;Reactive Oxygen Species;Repression;Respiration;response;Role;sarcopenia;Scanning;Signal Transduction;Skeletal Muscle;skeletal muscle wasting;SLC25A4 gene;Starvation;Stress;Stress Response Signaling;stressor;Testing;Tissues;transcriptome sequencing;Transgenic Mice;Translations;wasting

PROJECT_TITLE: Mechanism of mitochondria-induced proteostatic signaling and progressive muscle atrophy during aging.


NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_NAME: DANA-FARBER CANCER INST

PHR: Project Narrative: Ewing sarcoma is the second most common bone tumor occurring in children, but there have been no improvements in treatments or survival rates for more than a decade for patients with advanced disease. While immunotherapy with chimeric antigen receptor (CAR) T cells has mediated major advances in pediatric leukemia, it has not yet proven effective in Ewing sarcoma. We will explore approaches to apply CAR T cells targeting the validated target GD2 and other ganglioside targets to treat this highly recalcitrant pediatric cancer.

PI_NAMEs: MAJZNER, ROBBIE G. (contact);STEGMAIER, KIMBERLY

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: Adolescent;Adult;advanced disease;Antibodies;Antigens;Biological;bone;Bone neoplasms;Brain Neoplasms;cancer cell;Caring;Cell Therapy;Cells;chemotherapy;Child;Childhood Leukemia;Childhood Solid Neoplasm;chimeric antigen receptor;chimeric antigen receptor T cells;Chromatin;Clinical;Clinical Trials;Combination Drug Therapy;combinatorial;Common Neoplasm;Credentialing;Data;Development;Diagnosis;Diffuse intrinsic pontine glioma;Disease;Drug Targeting;Engineering;Enzymes;Epigenetic Process;Ewings sarcoma;exhaustion;Failure;G(M2) Ganglioside;Ganglioside GD2;Gangliosides;gene translocation;Genetic Engineering;Genetic Transcription;Glycolipids;Goals;Heterogeneity;Immune checkpoint inhibitor;Immune response;Immunotherapeutic agent;Immunotherapy;improved;In Vitro;in vivo;inhibitor;insight;Late Effects;Left;leukemia relapse;leukemia/lymphoma;Link;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Metastatic Ewing's Sarcoma;Methods;Modeling;Molecular;mouse model;Mutation;neoplastic cell;Neuroblastoma;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Operative Surgical Procedures;overexpression;Pathway interactions;Patients;postnatal;primary bone cancer;Radiation therapy;Receptor Signaling;Recurrence;Recurrent disease;Regulation;Relapse;relapse prevention;Repression;resistance mechanism;response;Safety;Sampling;sialogangliosides;Signal Transduction;Solid Neoplasm;sugar;Surface;Survival Rate;T cell response;T-Lymphocyte;Testing;Tissues;Toxic effect;Translating;tumor;young adult;ZAP-70 Gene

PROJECT_TITLE: Immunotherapeutic targeting of gangliosides in Ewing Sarcoma


NIH_SPENDING_CATS: Cancer;Prevention

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: NARRATIVE/RELEVANCE STATEMENT Innovations in cancer prevention, treatment, and cure are at risk because an insufficient number of people are entering and persisting in the biomedical research workforce. To address this, we have launched the Duke Preparing Research scholars In bioMEdical sciences (PRIME): Cancer Research Program, a sustainable program that will develop a pipeline in academic careers and enhance their success by providing early exposure to cancer research experiences, mentorship, skills-building, and scientific networks. This program will recruit and prepare the next generation of scientists to advance cancer care and will serve as a model for expanding across disciplines to develop the biomedical workforce and meet the nation’s needs for innovation in medicine.

PI_NAMEs: BLOBE, GERARD C (contact);SOMARELLI, JASON ANDREW

PROGRAM_OFFICER_NAME: ELJANNE, MARIAM

PROJECT_TERMS: Academy;Address;Admission activity;Adolescence;Advanced Malignant Neoplasm;anti-cancer research;Area;Basic Cancer Research;Biomedical Research;Cancer Biology;cancer care;Cancer Control;Cancer Death Rates;cancer diagnosis;cancer prevention;Cancer Research Project;cancer risk;Cancer Science;Cancer Survivor;cancer therapy;cancer type;career;Career Choice;career development;Caring;Cause of Death;Cessation of life;Childhood;Clinical;cohort;Critical Thinking;Death Rate;Dedications;Detection;Development;didactic education;Discipline;Education;education research;Educational Curriculum;Evaluation;evidence base;experience;Exposure to;Face;falls;Funding;Future;Goals;graduate school;Health;Image;Immunooncology;improved;Incidence;Individual;innovation;Institution;interest;Internet;Knowledge;laboratory experience;Laboratory Research;Link;Malignant Neoplasms;Medical;medical schools;Medical Students;Medicine;meetings;Mentors;Mentorship;Methodology;Modality;model development;Modeling;Morbidity - disease rate;mortality;network models;neuro-oncology;next generation;Occupations;Outcome;outreach;Pathway interactions;peer;peer coaching;peer networks;Persons;Physicians' Offices;Positioning Attribute;Postbaccalaureate;precision oncology;premature;Prevalence;Prevention;Professional Competence;Program Sustainability;programs;Radiation Oncology;recruit;Research;Research Personnel;Research Training;Resources;Risk;Role;Science;Scientist;skills;STEM field;Structure;Students;success;summer research;Talents;Technical Expertise;Techniques;Therapeutic;tool;Training;Training and Infrastructure;undergraduate student;United States;Universities;virtual;virtual platform

PROJECT_TITLE: Duke PRIME Cancer Research Program

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Institutional Training and Education Study Section (F)[NCI-F]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Machine Learning and Artificial Intelligence;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: LOGAN

ORG_NAME: UTAH STATE UNIVERSITY

ORG_STATE: UT

PHR: PROJECT NARRATIVE Many biological behaviors and functions are realized through the formation and changes of the shapes of biological systems. However, the mechanism of how some biological shapes are determined and changed in a limited body space remains unknown. How these shape-changes direct biological behaviors are also poorly understood. This work aims to uncover these processes and answer mechanistic questions that have not yet been fully addressed, with the hope of developing a new strategy for investigating biosciences. .

PI_NAMEs: HUANG, YU  (contact)

PROJECT_TERMS: Address;Area;Behavior;biobehavior;Biological;Biological Process;Biological Sciences;biological systems;Biophysics;Brain;Bulla;cell behavior;Cell membrane;Complex;cranium;Data;data-driven model;Development;Epigenetic Process;fascinate;Genetic;In Vitro;in vivo;in vivo Model;interstitial;Machine Learning;mathematical model;Membrane;Modeling;Molecular;Morphology;Process;Shapes;Stimulus;System;Tissues;tool;Work

PROJECT_TITLE: Uncover Spatial-Constraint Related Morphome Using Tissue-on-a-Chip Platform and Data-Driven Mathematical Modeling

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


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Gene Therapy;Genetics;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE – PROJECT 3 Despite decades of research, prognosis for patients suffering from malignant glioblastoma (GBM) remains poor. Oncolytic viral (OV) therapy is an exciting therapeutic modality that has been approved for non resectable melanoma in USA and for brain tumors in japan. The proposed research in this project will investigate impact of this therapy on tumor and stromal cells and with a goal to improve virotherapy.

PI_NAMEs: KAUR, BALVEEN  (contact)

PROJECT_TERMS: Adenosine;adenosine deaminase;Affect;Alternative Therapies;anti-cancer;anti-PD1 therapy;Antibodies;Antigen Presentation;Avastin;bevacizumab;Biological;Brain Neoplasms;Cells;Clinic;Collaborations;Decision Making;Development;Diagnosis;Educational process of instructing;Equilibrium;exosome;extracellular;Extracellular Matrix;Fab Immunoglobulins;G207;Generations;Glioblastoma;Glioma;Goals;Grant;Human;IgG1;Immune;Immune response;Immune system;immune system function;Immunoglobulin Fragments;improved;Individual;Infection;Inflammatory;Intracranial Neoplasms;Investigation;Japan;Knockout Mice;Length;Licensing;Malignant - descriptor;Malignant Glioma;Marketing;Mediating;Melanoma;Metabolic;Metastatic Melanoma;Modality;Mus;Neoplasm Metastasis;neoplastic cell;novel;Oncolytic;oncolytic herpes simplex virus;oncolytic virotherapy;overexpression;patient prognosis;Patients;phase 1 study;Primary Brain Neoplasms;Primary Neoplasm;Process;Production;Program Research Project Grants;programs;RANTES;Recurrence;Research;research clinical testing;Research Personnel;Role;Safety;Signal Transduction;Solid Neoplasm;Stromal Cells;synergism;Testing;Therapeutic;Translating;Treatment Efficacy;tumor;tumor eradication;Tumor Immunity;tumor microenvironment;vector;Viral;Virotherapy;Virus;Work

PROJECT_TITLE: Project 3: Circumventing extracellular Adenosine barrier to oncolytic virotherapy


FUNDING_MECHANISM: SBIR-STTR RPGS

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

ORG_CITY: WESTON

ORG_NAME: APPLIKATE TECHNOLOGIES, INC.

PHR: Project Narrative Applikate Technologies has developed a new, direct-to-digital platform for processing and imaging tissue biopsies that will reduce errors, lower costs, and enable same-day diagnosis for patients waiting to hear if they have cancer. This proposal will provide funds to develop risk and quality management systems and to collect the clinical and non-clinical validation data, all of which is necessary for regulatory approval by the FDA.

PI_NAMEs: LEVENE, MICHAEL JOHN (contact);TORRES, RICHARD

PROGRAM_OFFICER_NAME: ZHAO, MING

PROJECT_TERMS: 3-Dimensional;Address;Adult;Anxiety;Authorization documentation;Biopsy;breast cancer diagnosis;cancer diagnosis;cancer subtypes;Client;Clinical;clinical development;clinical diagnostics;Consultations;Contracts;cost;Country;Data;design;Development;Devices;Diagnosis;Diagnostic;Diagnostic Errors;digital imaging;digital pathology;digital platform;Documentation;Engineering;Equipment;Equipment and Supplies;Evaluation;experience;Failure;falls;Feedback;Funding;General Practitioners;health economics;Health Sciences;Hearing;Hematoxylin and Eosin Staining Method;Histology;Hospitals;Hour;Human;Image;Imaging Device;imaging platform;Immunohistochemistry;improved;Instruction;interest;Laboratories;machine vision;Malignant Breast Neoplasm;Malignant Neoplasms;manufacture;Manufacturer;Marketing;medical schools;Molecular Analysis;Morphologic artifacts;multiphoton microscopy;Noise;novel;Output;Pathologic;Pathologist;Pathology;Patient Care;Patients;Phase;Preparation;preservation;pressure;Privatization;Procedures;prospective;Prostatic Neoplasms;Qualifying;Readiness;Recording of previous events;Records;Remote Consultation;Research;Research Contracts;Research Design;Resolution;response;Risk;Risk Management;Savings;Scanning;Signal Transduction;Slice;Slide;Small Business Innovation Research Grant;Specimen;stem;submicron;System;Technology;Testing;Thick;Tissue imaging;tissue processing;Tissues;Translating;United States National Institutes of Health;Validation;verification and validation;Wait Time;Waxes;whole slide imaging;Work;Workload

PROJECT_TITLE: Commercial Readiness for Direct-to-Digital Pathology


PHR: PROJECT NARRATIVE – PROJECT 4 Despite decades of research, prognosis for patients suffering from malignant glioblastoma (GBM) remains poor. We engineered two innovative clinical-grade oncolytic viruses with multiple mechanisms of action and will evaluate their safety and efficacy against GBM. The proposed preclinical research arms oncolytic virus with powerful payloads to maximize immune responses in the tumor microenvironment to enhance oncolytic virotherapy efficacy for malignant GBM.

PI_NAMEs: CALIGIURI, MICHAEL A (contact)

PROJECT_TERMS: Adenosine;Adoptive Cell Transfers;Anti-CD47;anti-PD-1;anti-tumor immune response;Antibodies;antibody-dependent cell cytotoxicity;antibody-dependent cellular phagocytosis;arm;Binding;Biodistribution;Biological Markers;Brain;CCR1 gene;CD47 gene;Cells;Cetuximab;chemokine;chimeric antigen receptor T cells;Circulation;Cities;Clinical;Clinical Trials;Combined Modality Therapy;cytokine;Data;design;Development;Dose;Eating;efficacy study;Engineering;Epidermal Growth Factor Receptor;Fc Receptor;Future;Glioblastoma;Goals;Good Manufacturing Process;Growth Factor;Herpes Simplex Infections;Herpesvirus 1;Human;IgG1;Immune;immune cell infiltrate;immune checkpoint blockade;Immune response;Immunity;Immunocompetent;Immunologic Stimulation;immunoregulation;Immunosuppression;Immunotherapy;improved;In Vitro;in vivo;Inflammatory;innovation;Investigational Drugs;Investments;Length;Link;Macrophage;Malignant - descriptor;Malignant Glioma;Malignant neoplasm of brain;Malignant Neoplasms;manufacture;Mediating;migration;Modeling;Monitor;Monoclonal Antibodies;mouse model;Mus;Natural Killer Cells;neoplastic cell;NK Cell Activation;Normal tissue morphology;novel;oncolysis;Oncolytic;oncolytic virotherapy;Oncolytic viruses;Outcome;patient prognosis;Patients;PD-1/PD-L1;peripheral blood;pharmacokinetics and pharmacodynamics;pre-clinical research;preclinical efficacy;preclinical safety;preclinical study;prevent;Production;PTPNS1 gene;Publications;Publishing;RANTES;receptor;recruit;Research;response;Safety;Sampling;scaffold;Schedule;Signal Transduction;Solid Neoplasm;Surface;synergism;System;T-Lymphocyte;Testing;Tissues;Toxic effect;trafficking;treatment optimization;tumor;tumor microenvironment;tumor progression;Tumor-infiltrating immune cells;Viral;Virus;Virus Replication

PROJECT_TITLE: Project 4: Awakening immune responses to GBM by enhancing immune cell trafficking and activation with oHSV armed with Cetuximab-CCL5 and anti-CD47 antibody payloads.


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: ANN ARBOR

ORG_NAME: EVOQ THERAPEUTICS, INC.

ORG_STATE: MI

PHR: PROJECT NARRATIVE The objective of this project is to develop an effective treatment for type-1 diabetes which currently has no cure. The proposed research is most relevant to public health as these studies will generate new fundamental knowledge in drug development, address current technical limitations in therapies against autoimmune diseases, and lead to new strategies to achieve long-term immune tolerance.

PI_NAMEs: DANIEL, WESTON  (contact)

PROGRAM_OFFICER_NAME: ARREAZA-RUBIN, GUILLERMO

PROJECT_TERMS: Acute;Address;Adjuvant;Affect;Age;analytical method;Antigen Presentation;Antigen-Presenting Cells;Antigens;Apolipoprotein A-I;Autoantigens;Autoimmune Diseases;Autoimmunity;autoreactive T cell;autoreactivity;Beta Cell;Biological Assay;Bystander Suppression;cancer vaccination;CD8-Positive T-Lymphocytes;Cell Physiology;Clinical Chemistry;clinical development;Clinical Protocols;clinical translation;cytokine;Data;Dendritic Cells;Disease;Disease susceptibility;Dose;drug development;Drug Kinetics;effective therapy;Epitopes;Evaluation;Experimental Autoimmune Encephalomyelitis;Feedback;Formulation;Future;Goals;good laboratory practice;High Density Lipoproteins;Human;Hyperglycemia;IgG autoantibodies;IL17 gene;Immune mediated destruction;Immune response;Immune Tolerance;Immunity;immunological intervention;Immunologics;immunomodulatory strategy;immunoregulation;Immunotherapy;Impairment;In Vitro;Inflammatory;Insulin;Insulin Infusion Systems;Insulin-Dependent Diabetes Mellitus;Interferon Type II;Knowledge;Laboratories;lead candidate;Link;Lymph;lymph nodes;manufacture;manufacturing process;meetings;Modeling;Mononuclear;mouse model;Mus;nanodisk;nanoparticle;novel strategies;Organ;Outcome;Pancreas;Pathogenicity;Pathology;Pathway interactions;Patients;peptidomimetics;Peripheral Blood Mononuclear Cell;Persons;Phagocytosis;Phase;Phospholipids;pre-Investigational New Drug meeting;prevent;Process;process optimization;programmed cell death ligand 1;Public Health;Rattus;Regimen;Regulatory T-Lymphocyte;Reporting;Research;restraint;Safety;standard of care;System;T cell response;T-Lymphocyte;Therapeutic;Toxicology;Treatment Efficacy;tumor;tumor-immune system interactions;Vaccines

PROJECT_TITLE: New approach for immune modulation against T1D

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-U(10)]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cystic Fibrosis;Lung;Machine Learning and Artificial Intelligence;Rare Diseases

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: PROJECT NARRATIVE Improved computational models of high-glycosylation proteins that capture their molecular structure-dynamics are imperative to acquire detailed understanding of these critical biomedical entities. We will use a combination of biophysics-based and machine learning driven approaches to build predictive models of glycoproteins, using mucins as our study case. These models will be harnessed to elucidate the molecular underpinnings that drive their function in normal and diseased conditions, allowing for better therapeutic strategies, as well as aid in designing novel mucin-mimetic biomaterials.

PI_NAMEs: CHAKRABORTY, SRIRUPA  (contact)

PROGRAM_OFFICER_NAME: GERSHENSON, ANNE

PROJECT_TERMS: Biocompatible Materials;Biological Process;Biophysics;Case Study;Charge;Combinatorics;Comprehension;Computer Models;computerized tools;conformational conversion;Cystic Fibrosis;Data;design;Disease;Equilibrium;experimental study;Gel;Glycopeptides;Glycoproteins;glycosylation;Grain;improved;in silico;intermolecular interaction;Machine Learning;Malignant Neoplasms;Mediating;Methods;mimetics;Modeling;Molecular;Molecular Machines;Molecular Structure;Mucins;Mucositis;Mucous Membrane;multimodality;nanomaterials;novel;Pattern;Peptides;physical property;Play;Polymers;Polysaccharides;predictive modeling;Property;Protein Glycosylation;Resources;Role;Structure;sugar;System;Techniques;Therapeutic;tool

PROJECT_TITLE: Modeling the mucosal glycopeptide mesh for improved disease understanding and mucin-inspired biomaterial design


ORG_CITY: NEW HAVEN

ORG_DEPT: DERMATOLOGY

ORG_NAME: YALE UNIVERSITY

PHR: OVERALL: PROJECT NARRATIVE The goal of the Yale SPORE in Skin Cancer is to decrease morbidity and mortality from melanoma. We have assembled a group of interdisciplinary investigators to conduct a series of bench-to-bedside studies aimed at preventing melanoma and improving outcomes for patients in whom melanoma has metastasized. These studies will capitalize on advances made in the last funding period and build on the extensive resources, such as tumor samples, animal models, and novel drugs and technologies, developed in the past decade by YSPORE investigators.

PI_NAMEs: BOSENBERG, MARCUS W (contact);KLUGER, HARRIET M.

PROGRAM_OFFICER_NAME: KUZMIN, IGOR A

PROJECT_TERMS: Adaptive Immune System;Address;advanced disease;Agonist;Animal Model;anti-CTLA4;anti-PD-1;Antibodies;Antitumor Response;Award;Back;bench to bedside;Bioinformatics;Biological Assay;Biological Markers;Biology;biomarker development;Biometry;career;Cell Culture Techniques;Cells;Clinic;Clinical;clinical application;Clinical Trials;cohort;Collaborations;cytokine;cytokine therapy;Data;derepression;design;Development;digital pathology;Disease;Effector Cell;effector T cell;Environment;Epigenetic Process;Eye;Fostering;Funding;Future;Genetic;Goals;histone demethylase;Histone-Lysine N-Methyltransferase;Human;IL18 gene;Immune checkpoint inhibitor;Immune Evasion;Immunobiology;Immunocompetent;immunomodulatory therapies;Immunooncology;Immunotherapy;improved;improved outcome;Incidence;inhibitor;Innate Immune System;innovation;Institution;Interdisciplinary Study;Interferon Type II;interleukin-18 receptor;KDM5B gene;Macrophage;Malignant Neoplasms;medical schools;Melanoma;Melanoma Cell;Melanoma patient;Messenger RNA;Metastatic Melanoma;Methods;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Natural Immunity;Natural Killer Cells;neoantigens;Neoplasm Metastasis;neoplastic cell;new technology;new therapeutic target;next generation;novel;novel strategies;novel therapeutics;optimal treatments;Outcome;Pathway interactions;Patient Selection;Patient-Focused Outcomes;Patients;PD-1 inhibitors;PD-1/PD-L1;PD-L1 blockade;Phase I Clinical Trials;Pre-Clinical Model;predicting response;predictive marker;preservation;prevent;Productivity;Program Development;programs;Proteins;Regimen;Research;Research Personnel;Resistance;resistance mechanism;Resources;response;Retroelements;Sampling;Science;Series;SETDB1 gene;Signal Repression;Site;Skin Cancer;stem;Systemic Therapy;T cell infiltration;T-Lymphocyte;Technology;therapy resistant;Thinness;Tissues;TNFRSF5 gene;Toxic effect;Translating;translational cancer research;translational scientist;Treatment Protocols;tumor;Variant;Work;Yale Cancer Center

PROJECT_TITLE: Yale SPORE in Skin Cancer


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Skin Cancer

PI_NAMEs: BOSENBERG, MARCUS W (contact)

PROJECT_TERMS: Address;Administrator;Advocacy;Bioinformatics;Biometry;Cancer Hospital;career;Clinical;clinical infrastructure;Collaborations;Communication;Community Outreach;Consultations;data integration;data sharing;Dermatology;Development;Educational workshop;Ensure;Funding;Goals;Grant;Head and neck structure;Institution;Joints;Leadership;Malignant neoplasm of lung;medical schools;meetings;Melanoma;Monitor;National Cancer Institute;neoplasm resource;operation;outreach;patient outreach;Patients;Pharmaceutical Preparations;Program Evaluation;programs;Progress Reports;Publications;Regulation;Research;Research Personnel;Research Priority;Resource Sharing;Resources;scientific organization;Series;Services;Site;Skin Cancer;success;synergism;Technology;Translational Research;United States National Institutes of Health;Universities;Update;wasting;website development;Work;Yale Cancer Center

PROJECT_TITLE: Core A: Administrative Core


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Fragile X Syndrome;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Orphan Drug;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CAMBRIDGE

ORG_NAME: QUIVER BIOSCIENCE INC.

PHR: Project Narrative Q-State has developed a light-based technology to measure the electrophysiological activity of cultured neurons at an unprecedented scale. In this project, we will leverage these high throughput readouts in combination with loss-of-function genomic screens to generate single-cell resolution fingerprints for every transcribed gene in the human genome. Successful completion of this project will establish a platform to identify targets that specifically modulate disease-relevant, neurophysiological mechanisms and has potential to provide a novel basis for targeting the underlying disease biology for multiple CNS disorders.

PI_NAMEs: LEWARCH, CAITLIN LEIGH;WILLIAMS, LUIS ALBERTO (contact)

PROGRAM_OFFICER_NAME: ANDERSON, PAIGE MARIE

PROJECT_TERMS: Action Potentials;Address;Affect;analysis pipeline;analytical tool;Architecture;Area;automated analysis;Behavior;Benchmarking;Biochemical;Biological Assay;Biology;Candidate Disease Gene;Cell model;Cells;Central Nervous System;Central Nervous System Agents;Central Nervous System Diseases;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;convolutional neural network;Data;Data Set;Databases;deep learning;deep neural network;Dimensions;Disease;disease model;Disease Pathway;disease phenotype;Down-Regulation;drug discovery;Drug Targeting;Electrophysiology (science);Epilepsy;excitatory neuron;Eye;Fingerprint;FMR1 gene;Fragile X Syndrome;functional genomics;Gene Expression;gene function;Gene Targeting;Genes;Genetic;genetic approach;Genetic Screening;genetic testing;Genetic Transcription;genome wide screen;genome-wide;Genomics;Guide RNA;Heterogeneity;Human;Human Genome;human induced pluripotent stem cells;Individual;Induced pluripotent stem cell derived human neuron;Induced pluripotent stem cell derived neurons;Industrialization;instrument;Intervention;knock-down;Learning;Libraries;Light;Location;loss of function;Machine Learning;Maps;Marketing;Measurement;Measures;Mediating;Medical;Modality;Modeling;Molecular;Molecular Target;Nervous System Disorder;Neurodevelopmental Disorder;Neurons;neurophysiology;new therapeutic target;novel;nuclease;Optics;particle;Patients;Pharmaceutical Preparations;pharmacologic;Phase;Phenotype;Physiological;Physiology;Population;Predictive Value;Process;programs;Resolution;screening;Screening Result;Specificity;success;Synapses;System;Technology;Testing;Therapeutic;therapeutic development;therapeutic gene;therapeutic target;therapeutically effective;training data;transcriptomics;Translating;Validation;vector;Viral;Western Blotting;Work

PROJECT_TITLE: BRITE-Eye: An integrated discovery engine for CNS therapeutic targets driven by high throughput genetic screens, functional readouts in human neurons, and machine learning

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-NV-G(13)B]


PHR: PROJECT NARRATIVE – ADMINISTRATIVE CORE (CORE A) The primary objectives of the Administrative Core are to provide overall administrative and fiscal support to all of the Projects and Cores of this Program Project focused on the discovery and development of novel antibody therapies and theranostics for the treatment and diagnosis of solid tumors. This Core will serve as the communication hub for the Program Project and is essential to the success of the investigations proposed in this P01.

PROJECT_TITLE: Core A - Administrative Core


PHR: PROJECT NARRATIVE – CORE 1 The American Cancer Society predicts there will be >12,000 deaths/yr from brain cancer. The recent Phase-1 clinical trial with oncolytic Herpes Simplex Virus (oHSV) rQNestin34.5V2 has shown considerable promise. The goal of the P01 renewal is to improve upon this process. Doing so requires high-titer purified stocks, grown and purified by one Core 1 otherwise considerable variation in purity, stability, sterility and identity occurs. Core 1 will provide the projects with highly purified oHSV stocks based on the detailed protocols we have developed for oHSV production, purification and quality assessment.

PI_NAMEs: GOINS, WILLIAM F. (contact)

PROJECT_TERMS: Adopted;American Cancer Society;Animals;Bacterial Artificial Chromosomes;Biodistribution;Biological Assay;Cell Line;Cells;Cessation of life;Cities;Clinical Trials;Contracts;cost;CRISPR interference;CRISPR-mediated transcriptional activation;Cyclic GMP;Data;Development;Dexamethasone;Dextran Sulfate;DNA;efficacy study;efficacy testing;Engineering;Ensure;Excision;exosome;experimental study;Freeze Drying;Gene Expression;Genes;Genome;Glioblastoma;Glycerol;Goals;Herpesvirus 1;HSV vector;Human;IgG1;Immune response;Immunity;improved;in vivo;Individual;Infection;inhibitor;interest;Interferons;Laboratories;Lentivirus;Libraries;Malignant Glioma;Malignant neoplasm of brain;manufacture;manufacturing capabilities;manufacturing facility;Methodology;Modeling;Monoclonal Antibodies;neoplastic cell;Nervous System Neoplasms;Normal Cell;novel;Oncolytic;oncolytic herpes simplex virus;oncolytic virotherapy;Oncolytic viruses;particle;Pathway interactions;Phase;Phase I Clinical Trials;phase I trial;Phase I/II Clinical Trial;Positioning Attribute;pre-clinical;preclinical efficacy;Procedures;Process;Production;Proteins;Protocols documentation;RANTES;Reagent;Research;Research Personnel;response;Safety;safety testing;scale up;Simplexvirus;Site;Standardization;Sterility;Stress;success;System;Technology;Temperature;Test Result;Testing;Time;Toxic effect;transcriptome sequencing;Translations;tumor;Variant;vector;Vendor;Viral;Virus;Virus Replication;Work

PROJECT_TITLE: Core 1: oHSV Production Core


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Data Science;Networking and Information Technology R&D (NITRD)

ORG_CITY: GAINESVILLE

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE Big Data problems are ubiquitous in biomedical research, but current methodologies based on pair-wise similarity calculations are too computationally expensive, so they are ill-equipped to handle the amount of data generated by state-of-the-art simulations and experiments. We seek to develop, implement, and apply novel highly-efficient computational techniques tailored for large-data applications based on our extended similarity framework. This will lead to more general and robust drug design protocols, a better understanding of complex biological processes (including protein folding and structure determination), and versatile ways to process mass spectrometry images of diverse tissues, leading to new insights in pathophysiology and novel diagnosis tools.

PI_NAMEs: MIRANDA QUINTANA, RAMON ALAIN (contact)

PROJECT_TERMS: Big Data;Methods;Science

PROJECT_TITLE: Tackling Big Data problems in biomedical sciences with extended similarity methods

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Immunotherapy;Precision Medicine;Skin Cancer

PHR: PROJECT 2: PROJECT NARRATIVE This proposed research is relevant to public health because it can evaluate the KDM5B histone demethylase as an attractive drug target for cancer treatment, evaluate new approaches to enhance anti-tumor immunity, and provide new melanoma biomarkers. Thus, the proposed studies are relevant to NCI’s mission because they will have major impact on our understanding of the cause, diagnosis and treatment of cancer.

PI_NAMEs: YAN, QIN  (contact)

PROJECT_TERMS: anti-PD-1;anti-tumor immune response;Biological Assay;Biological Markers;Biopsy;cancer infiltrating T cells;cancer therapy;Cells;Clinic;Clinical;Clinical Trials;cohort;CXCL10 gene;Data;derepression;Development;Diagnosis;Drug Targeting;Drug usage;Epigenetic Process;epigenetic regulation;experimental study;Future;Genes;Goals;Growth;histone demethylase;histone methyltransferase;Human;human data;Immune;Immune checkpoint inhibitor;Immune Evasion;Immune response;immunogenic;Immunologic Markers;Immunotherapy;improved;innovation;Interferon Type I;Interferons;KDM5B gene;Lead;Melanoma;melanoma biomarkers;Melanoma Cell;Melanoma patient;Metastatic Melanoma;Mission;Modeling;Molecular;Mus;novel;novel marker;novel strategies;novel therapeutic intervention;Patient Selection;Patients;PD-1 blockade;Pharmaceutical Preparations;pre-clinical;predicting response;predictive marker;Prognosis;programmed cell death protein 1;Public Health;recruit;Regimen;Repression;Research;Resistance;Resistance development;response biomarker;Retroelements;Sampling;SETDB1 gene;Signal Transduction;Skin Cancer;synergism;targeted treatment;Testing;Therapeutic;therapeutic target;Time;transcriptome sequencing;Translating;tumor;Tumor Immunity

PROJECT_TITLE: Project 2. Harnessing Epigenetic Regulation of Endogenous Retroelements in Melanoma


ORG_CITY: PHILADELPHIA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Overall Narrative Our goal is to develop practice changing, next-generation immunotherapies for hematologic malignancies which strike more than 200,000 people every year in the United States. Our approach involves the development of next-generation therapies with chimeric antigen receptor (CAR) T cells, involving innovative combinations of CAR T cells and genetic editing with CRISPR/Cas9 technology and base editing to be tested in several clinical trials. Our team has provided paradigm-shifting impact in B cell malignancies and these projects have the potential to transform therapies for numerous cancers beyond acute leukemia.

PI_NAMEs: JUNE, CARL H. (contact)

PROGRAM_OFFICER_NAME: HENDERSON, LORI A

PROJECT_TERMS: Acute leukemia;Acute Myelocytic Leukemia;Acute T Cell Leukemia;Address;Adoptive Transfer;antitumor effect;authority;Autoimmune Diseases;B lymphoid malignancy;B-Cell Acute Lymphoblastic Leukemia;Back;base editing;bench to bedside;Biological;Biometry;Blood;cancer cell;cancer immunobiology;cancer immunotherapy;CAR T cell therapy;CD19 gene;Cell Therapy;Cells;chimeric antigen receptor;chimeric antigen receptor T cells;Chronic Lymphocytic Leukemia;Clinic;Clinical;clinical investigation;Clinical Trials;Collaborations;CRISPR/Cas technology;CTLA4 gene;Development;Discipline;Disease;efficacy testing;engineered T cells;Engineering;FDA approved;Funding;Future;Gene Modified;gene therapy;Generations;Genes;Genetic;genome editing;Gills;Goals;Hematologic Neoplasms;Hematopoiesis;Hematopoietic Neoplasms;Hematopoietic System;Human Genome;Immune;Immunologics;Immunotherapy;improved;In complete remission;indexing;Individual;innovation;Interleukin-2;International;Joints;Journals;Laboratories;leukemia;leukemia/lymphoma;Licensing;Lymphoblastic Leukemia;Lymphoma;Malignant Neoplasms;manufacturing facility;Marrow;Mediating;Medical;Medicine;Modification;Monitor;mRNA lipid nano particle vaccine;multidimensional data;Multiple Myeloma;Mutate;Myeloid Leukemia;New England;next generation;novel;novel therapeutics;overexpression;Paper;Patients;Persons;preclinical study;programs;PTPRC gene;Publications;Publishing;rational design;Refractory;Relapse;Research;Research Personnel;Resistance;Resource Sharing;Safety;Sampling;Services;Small-Cell Lymphoma;Solid;Source;standard of care;Surface Antigens;synthetic biology;T-Lymphocyte;Technology;Testing;Therapeutic;tool;Toxic effect;Translating;tumor;United States

PROJECT_TITLE: Enhancing Chimeric Antigen Receptor T Cell Therapies for HematologicMalignancies: Beyond CART 19


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Clinical Research;Gene Therapy;Genetics;Human Genome;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE – CORE 2 Glioblastoma (GBM) is amongst the most lethal forms of cancer. The Core 2 Glioblastoma Biorepository proposes to provide services of neuropathology review, digital pathology, tissue and cell line banking and creation of patient derived xenografts for use by the Projects to develop methods to improve effectiveness of oHSV in GBM. In addition, we will provide expert immuno-oncology approaches to the P01 such as novel multiplex fluorescent imaging, genomics, and model modifications to understand resistance to oHSV therapy.

PI_NAMEs: LIGON, KEITH LLOYD (contact)

PROJECT_TERMS: 3-Dimensional;Autopsy;biobank;Biology;cBioPortal;Cd68;CD8B1 gene;Cell Line;cell preparation;Cells;Clinical;Clinical Research;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Collection;Combined Modality Therapy;Consent;CTLA4 gene;Data;Dedications;deep learning algorithm;Development;digital pathology;DNA sequencing;Effectiveness;Ensure;Epidermal Growth Factor Receptor;epigenomics;Evaluation;Fingerprint;fluorescence imaging;Funding Mechanisms;Future;Genomics;Giant Cells;Glioblastoma;Glioma;Goals;Grant;high dimensionality;Human;Human Cell Line;human model;humanized mouse;Immune;Immunofluorescence Immunologic;Immunohistochemistry;Immunology;Immunooncology;immunopathology;Immunotherapy;improved;In Vitro;in vitro Model;in vivo;Individual;Infection;Institution;Institutional Review Boards;Investigation;liquid crystal polymer;Maintenance;Malignant Glioma;Malignant Neoplasms;member;Methods;Modeling;Modification;Molecular;Molecular Analysis;Mouse Cell Line;mouse model;Mus;mutant;Myelogenous;neoplastic cell;neuropathology;Neurosphere;novel;oncolytic herpes simplex virus;oncolytic virotherapy;Oncolytic viruses;Operative Surgical Procedures;Pathologic;Pathology;patient derived xenograft model;patient subsets;Patients;Pattern;Phenotype;programmed cell death ligand 1;programmed cell death protein 1;programs;prospective;Protocols documentation;PTEN gene;receptor;repository;Research Personnel;Research Project Grants;Resistance;Resources;response;Sampling;Services;single nucleus RNA-sequencing;Site;Stains;Study models;targeted treatment;Therapeutic;Tissues;transcriptome sequencing;Transgenic Model;tumor;Tumor-Derived;Tumorigenicity;United States National Institutes of Health;Validation;Viral;Virus;Xenograft procedure

PROJECT_TITLE: Core 2: Glioblastoma Biorepository Core


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Cost Effectiveness Research;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Rural Health;Social Determinants of Health

ORG_CITY: Columbus

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE The proposed study will identify multilevel strategies that can help optimize mailed FIT programs. In doing so, it will assess the efficacy and cost-effectiveness of two promising strategies, FIT kit materials and patient navigation delivery mode. Results will provide an evidence base that can guide the design, implementation, scalability, and sustainability of future mailed FIT programs.

PI_NAMEs: KATZ, MIRA L;REITER, PAUL L (contact)

PROGRAM_OFFICER_NAME: KOBRIN, SARAH

PROJECT_TERMS: Address;Adult;Age;Appalachian Region;barrier to care;Cancer Etiology;cancer health disparity;Cessation of life;Characteristics;Colonoscopy;Colorectal Cancer;colorectal cancer screening;Communities;comparative cost effectiveness;cost;cost effective;cost effectiveness;County;Death Rate;design;Diagnostic Reagent Kits;Education;efficacy evaluation;evidence base;experience;Future;Geographic Locations;Health;health care availability;Health Insurance;Home;improved;Incidence;innovation;Instruction;interest;Intervention;Malignant Neoplasms;Medical;men;novel;outreach program;Pamphlets;Participant;patient navigation;patient navigator;Patients;Persons;pilot test;Population;programs;Randomized;randomized trial;Recommendation;Research;response;Risk;routine screening;Rural;screening;Screening for cancer;screening guidelines;Services;System;Telephone;Testing;Text;Text Messaging;Time;Transportation;Travel;United States;user-friendly;Visual;Woman;Work

PROJECT_TITLE: Strategies for Optimizing a Mailed FIT Program in Appalachia

STUDY_SECTION: HHD

STUDY_SECTION_NAME: Healthcare and Health Disparities Study Section[HHD]


NIH_SPENDING_CATS: Cancer;Clinical Research;Clinical Trials and Supportive Activities;Immunotherapy;Skin Cancer

PHR: PROJECT 3: PROJECT NARRATIVE Although many patients with metastatic melanoma are faring far better than a decade ago due to wide spread use of immunotherapies that target a molecule called PD-1, over half the patients either have tumors that are insensitive upfront or develop resistance over time. We propose to take a new approach to overcoming resistance in patients previously treated with immunotherapy using a novel drug developed at Yale University (DR-18/ST-067) that activates the immune system in an anti-PD-1 independent manner. We will start by conducting mechanistic studies to determine how DR-18 works to enhance the activity of anti-PD-1 in mouse models, followed by a clinical trial of the combination, with the goal of improving survival in melanoma patients whose disease has progressed on anti-PD-1.

PI_NAMEs: RING, AARON MICHAEL (contact)

PROJECT_TERMS: Activated Natural Killer Cell;Address;Agonist;Animal Model;antagonist;anti-PD-1;antigen-specific T cells;Award;Biological Markers;Biopsy;Blood;Blood specimen;cancer therapy;career;Caring;CD8B1 gene;Cell Physiology;Cells;Characteristics;Clinical;Clinical Trials;clinically relevant;Combined Modality Therapy;CTLA4 gene;cytokine;Development;Disease;Disease Resistance;Dose;effector T cell;efficacy evaluation;Engineering;Evaluation;experimental study;Feedback;first-in-human;Funding;Goals;Human;IL18 gene;Immune;immune checkpoint;Immune checkpoint inhibitor;Immune system;Immunity;Immunotherapeutic agent;Immunotherapy;improved;Interferon Type II;interleukin-18 binding protein;interleukin-18 receptor;Knock-out;Lead;Licensing;Malignant Neoplasms;Melanoma;Melanoma patient;Memory;Metastatic Melanoma;Methods;MHC Class I Genes;Modeling;mouse model;Mus;Mutation;Natural Killer Cells;neoplastic cell;NK Cell Activation;novel;novel strategies;novel therapeutics;participant enrollment;patient subsets;Patients;PD-1 blockade;PD-1 inhibitors;pembrolizumab;Pharmaceutical Preparations;Phase;phase I trial;Phase I/II Clinical Trial;Pre-Clinical Model;preclinical study;programmed cell death protein 1;programs;Recombinant Interleukin-18;Recommendation;Recurrent disease;Refractory;Regimen;Resistance;Resistance development;response;Sampling;Series;single-cell RNA sequencing;Site;Skin Cancer;stem;synergism;T cell response;T memory cell;T-Lymphocyte;Testing;Therapeutic;therapy resistant;Time;transcriptomics;tumor;tumor microenvironment;Tumor-Infiltrating Lymphocytes;Universities;Unresectable;Up-Regulation;Work

PROJECT_TITLE: Project 3. Overcoming Melanoma Treatment Resistance with Cytokine Immunotherapy


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Cancer;Brain Disorders;Cancer;Gene Therapy;Genetics;Immunotherapy;Neurosciences;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE – CORE 3 The Biostatistics and Bioinformatics Core will provide critical support for planning and design of experiments and studies, statistical and bioinformatical analyses and display of data, and data management and integrity. This support is designed to ensure that studies yield reliable conclusions, resources are efficiently used, and exploratory analyses uncover important leads.

PI_NAMEs: MO, XIAOKUI  (contact)

PROJECT_TERMS: Address;Basic Science;Bioinformatics;Biological;Biometry;Cells;Clinical;Clinical Data;Collaborations;combat;complex data;Data;Data Analyses;Data Display;data exploration;data integration;data integrity;data management;data quality;design;Development;Ensure;Experimental Designs;experimental study;Faculty;Formulation;Goals;high dimensionality;Human Resources;improved;Informatics;innovation;Investigation;Knowledge;Maintenance;Malignant Glioma;Measurement;meetings;Methodology;Methods;Modeling;novel;oncolytic virotherapy;Outcome Measure;Patients;pre-clinical;primary outcome;Procedures;Publishing;Reliability of Results;Reporting;repository;Research;Research Personnel;Resources;Sample Size;Sampling;Science;Secure;Security;Services;Statistical Methods;Statistical Models;Statistical sensitivity;Structure;Testing;Visual;Work

PROJECT_TITLE: Core 3: Biostatistics and Bioinformatics Core