NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer

PHR: Project Narrative Cancer recurrence is a major problem in the clinical management of most types of cancer, but its mechanism remains unclear. Anastasis is a newly discovered cell recovery mechanism that dying cancer cells could adopt to escape cell death-inducing cancer therapy by reversing apoptosis and therefore contribute to the recurrence, but it is technically challenging to test this iconoclastic hypothesis, because at the present time there is no practical way to identify anastatic cancer cells. Here, we will apply a novel biosensor to detect and track anastatic cells – an essential tool to examine the contribution of anastasis in cancer cells to the recurrence.

PI_NAMEs: TANG, HO LAM  (contact)

PROGRAM_OFFICER_NAME: SORG, BRIAN S

PROJECT_TERMS: Adopted;Animal Model;Animals;Antineoplastic Agents;Apoptosis;Apoptotic;Back;Biosensor;Bulla;cancer cell;Cancer cell line;cancer drug resistance;Cancer Etiology;cancer recurrence;Cancer Relapse;cancer therapy;cancer type;CASP3 gene;Caspase;Cell Death;Cell Death Induction;Cell Membrane Permeability;cell suicide;Cell Survival;Cells;Cellular Morphology;Cessation of life;Characteristics;Clinical Management;clinically relevant;cytochrome c;Development;Disseminated Malignant Neoplasm;Drosophila genus;Event;Excision;Exhibits;experience;fighting;Foundations;Future;Greek;Health;Human;improved;In Vitro;in vivo;in vivo imaging;Label;Life;live cell imaging;Malignant neoplasm of cervix uteri;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Methods;Morphology;mouse model;Mus;Names;new therapeutic target;novel;novel therapeutics;Outcome;Outer Mitochondrial Membrane;Pathologic;Pathway interactions;Penetration;Pharmaceutical Preparations;Physical condensation;Process;Recovery;Recurrence;response;Schedule;Solid Neoplasm;stem cells;Stimulus;Study models;System;targeted agent;Techniques;Technology;Testing;Therapeutic;Therapeutic Effect;Time;timeline;tool;Treatment Failure;tumor progression;tumorigenic;Xenograft procedure

PROJECT_TITLE: Detecting Reversal of Apoptosis in Cancer Cells in Mice


ADMINISTERING_IC: AG

ARRA_FUNDED: N

ED_INST_TYPE: UNIVERSITY-WIDE

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;Cardiovascular;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurodegenerative;Neurosciences;Physical Activity;Prevention;Social Determinants of Health

ORG_CITY: BLOOMINGTON

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE (PUBLIC HEALTH RELEVANCE STATEMENT) Sexual and gender minority (SGM) caregivers of persons living with with Alzheimer’s Disease (AD) and AD Related Dementias (AD/ADRD) face complex and overlapping challenges to engaging in regular physical activity (PA), based on identity-related and role-related stressors. Following the NIH Stage Model, this research seeks first to explore unique barriers and facilitators to regular PA engagement faced by SGM AD/ADRD caregivers (Stage 0), then co-design (Stage Ia) and test feasibility (Stage Ib) of a novel intervention to meet these distinct needs. This research will provide timely understanding of unique, intersecting needs of SGM AD/ADRD caregivers and inform creation of a culturally relevant, feasible, and sustainable PA intervention designed to meet specific challenges faced by this vulnerable population.

PI_NAMEs: PICKETT, ANDREW C. (contact)

PROGRAM_OFFICER_NAME: GERALD, MELISSA S

PROJECT_TERMS: Address;Aerobic;Affect;Aging;Alzheimer's Disease;Alzheimer's disease caregiver;Alzheimer's disease related dementia;Anxiety;Area;Award;Behavior;Behavioral;Behavioral Model;Cardiovascular system;Career Mobility;career networking;Caregiver Burden;Caregivers;caregiving;Caring;Chronic;cisgender;Competence;Complex;Consensus;Critiques;Data;Dementia caregivers;dementia caregiving;depressive symptoms;design;Development;Doctor of Philosophy;Educational workshop;Engineering;Ensure;Evaluation;evidence base;Exercise;exercise intervention;experience;Extramural Activities;Face;Family;feasibility testing;Foundations;Funding;Gender Identity;gender minority group;gender minority health;Goals;Health;health disparity;health management;Heterosexuals;Human;implementation science;improved;Indiana;Individual;Inequity;innovation;interest;Intervention;Interview;iterative design;Knowledge;Literature;Lived experience;Measures;member;Mental Depression;Mental Health;Mentors;Mentorship;Methodology;Methods;microaggression;Modeling;mortality;Nature;novel;older adult;Outcome;Participant;perceived stress;Personal Satisfaction;Persons;Physical activity;physical conditioning;Population;Positron-Emission Tomography;Prevention;primary outcome;Professional Organizations;professor;Program Evaluation;programs;protective effect;prototype;Psychology;public health relevance;Quality of life;Recommendation;Recording of previous events;Research;Research Personnel;Research Training;Risk;Role;Sampling;Scanning;sedentary lifestyle;Sexual and Gender Minorities;sexual identity;sexual minority group;skills;social;Social Network;social stigma;Societies;sociologist;Specific qualifier value;Standardization;Stigmatization;Stress;stressor;Structure;Subgroup;suicidal;Surveys;technology intervention;Testing;therapy design;therapy development;Time;Training;United States National Institutes of Health;Universities;usability;Vulnerable Populations;Work

PROJECT_TITLE: Development of a Physical Activity Intervention to Meet the Unique Needs of Sexual and Gender Minority (SGM) Alzheimer's Disease and Related Dementias (AD/ADRD) Caregivers

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF PHARMACY

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: SEATTLE

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE The Specific Aims of this translational collaborative R61/R33 application will evaluate the disease-modifying potential of the selective blood-brain barrier penetrant Nrf2 activator, dimethyl fumarate (DMF), in an etiologically relevant rat model of drug resistant epilepsy. The novel studies proposed herein will: 1) optimize oral dosing of DMF to male and female rats when delivered in an innovative medication-in-food paradigm; 2) assess the ability of DMF to prevent or modify the development of chronic epilepsy and/or associated comorbidities when administered at the time of status epilepticus onset; 3) determine whether adjunctive oral DMF therapy reduces seizure burden and improves pharmacosensitivity when combined with the antiseizure medicines levetiracetam and lamotrigine in rats with established epilepsy. The studies proposed herein are novel as they aim to inform on the development of a first-in-class therapy to preserve cognitive function, limit disease progression and improve pharmacosensitivity in the patient with epilepsy that results from severe status epilepticus or other brain insults.

PI_NAMEs: SHEKH-AHMAD, TAWFEEQ  ;WHITE, H STEVE (contact)

PROGRAM_OFFICER_NAME: SPRIGGS, SHARDELL M

PROJECT_TERMS: acquired epilepsy;Acute;Affect;Animals;Anticonvulsants;Antioxidants;Anxiety;Behavioral;Benzodiazepines;Biological Availability;Blood;Blood - brain barrier anatomy;Brain;burden of illness;Cells;Chronic;clinically relevant;Cognitive;cognitive function;Combined Modality Therapy;comorbidity;Coupled;Data;Development;Diagnosis;Disease;Disease Progression;Dose;Drug Interactions;Drug Modelings;efficacy evaluation;efficacy study;Epilepsy;Epileptogenesis;Etiology;FDA approved;Female;Food;Fumarates;Grant;Impaired cognition;improved;Incidence;innovation;Intervention;Intractable Epilepsy;Kainic Acid;Laboratories;lamotrigine;Levetiracetam;male;Maximum Tolerated Dose;Medicine;Mental Depression;Modeling;Modification;Monitor;Neurologic;Newly Diagnosed;novel;novel strategies;novel therapeutic intervention;nuclear factor-erythroid 2;object recognition;Oral;Oral Administration;Oxidative Stress;Patients;Performance;Persons;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;pharmacologic;Phase;Play;Positioning Attribute;preservation;prevent;Prevention;programs;Property;Quality of life;Rattus;Resistance;Risk;Seizures;Severities;Sprague-Dawley Rats;Status Epilepticus;Stroke;System;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;Transcription Coactivator;transcription factor;treatment arm;treatment effect;Universities

PROJECT_TITLE: Evaluating the disease modifying properties of dimethyl fumarate (DMF) for the prevention and treatment of pharmacoresistant epilepsy

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders A Study Section[NSD-A]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: SAN ANTONIO

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE  In this study, we developed a first-in-class small-molecule inhibitor of EZH2, a histone methyltransferase that has been demonstrated by a myriad of studies to drive cancer development and progression. Instead of the C-terminal catalytic domain that current EZH2-targeting drugs interfere with, our compound binds to an N- terminal domain that is essential for the gene activation activity and methyltransferase-independent oncogenic effect of EZH2 in estrogen receptor a-negative (ERa-) breast cancer cells. Therefore, our prototype compound downregulated a group of genes that promote cancer cell migration and inhibited the malignant phenotypes of ERa- breast cancer cells that are insensitive to present EZH2 inhibitors. Results from our work will yield a new class of anticancer agents that specifically target a totally different functional domain of EZH2, which hold promise for broader clinical applications than current EZH2-targeted therapies.

PI_NAMEs: XU, KEXIN  (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Adverse event;Affinity;Aggressive behavior;analog;anti-cancer therapeutic;Antineoplastic Agents;Binding;Biological;Biological Assay;Breast Cancer Cell;Breast Cancer Model;C-terminal;cancer cell;cancer type;Catalytic Domain;cell motility;Chemicals;ChIP-seq;Clinical;clinical application;Competence;Complex;Computer Assisted;Computer-Aided Design;Data;design;Development;Drug Kinetics;Drug Targeting;ESR1 gene;Essential Genes;Exhibits;EZH2 gene;Failure;FDA approved;Gene Activation;Gene Expression Profiling;gene repression;Gene Silencing;Genes;genetic inhibitor;Genetic study;Genetic Transcription;Goals;high throughput screening;Histone H3;histone methylation;histone methyltransferase;Histones;Impairment;improved;in silico;in vivo;inhibitor;Instruction;Lead;Lysine;Malignant Breast Neoplasm;Malignant Neoplasms;malignant phenotype;Mediating;Methyltransferase;migration;Monitor;mouse model;mutant;Mutate;Mutation;Myeloproliferative disease;N-terminal;novel;novel anticancer drug;Oncogenes;Oncogenic;overexpression;Patients;Phenotype;Play;Polycomb;Proliferating;protein folding;Proteins;Proteomics;prototype;Reporting;Research;Research Personnel;Role;Second Primary Cancers;SET Domain;side effect;Signal Pathway;Site;small molecule inhibitor;Structure;Structure-Activity Relationship;targeted agent;targeted treatment;Toxic effect;Transactivation;Transcription Coactivator;transcriptome sequencing;tumor;Tumor Cell Migration;tumor progression;Tumor Promotion;tumorigenesis;Tumorigenicity;Work;X-Ray Crystallography;Xenograft procedure

PROJECT_TITLE: Development of a new class of EZH2 inhibitors in ERa-negative breast cancer.

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-A (O1)]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Precision Medicine;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CORAL GABLES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: PROJECT NARRATIVE Enhanced neuronal activity is a major mechanism facilitating the progression and therapeutic resistance of glioblastoma (GBM), the most lethal form of primary brain tumor. The objective of this proposal is to enlighten the molecular mechanisms driving the activation of the neuronal program at recurrence of GBM and to address whether and how the tumor cells shape their microenvironment to support glioma invasion through integration of multi-omics with protein interaction networks, prioritization of targetable proteins and integrative analysis of spatial and single cell transcriptomics. The successful completion of this proposal will elucidate the key molecular drivers prompting the increased neuronal activity at recurrence and the dynamics of the functional links between malignant and non-malignant cells during the progression of GBM.

PI_NAMEs: MIGLIOZZI, SIMONA  (contact)

PROGRAM_OFFICER_NAME: SCHMIDT, MICHAEL K

PROJECT_TERMS: Address;Affect;Algorithms;Astrocytes;Automobile Driving;Binding;Biological;Biopsy;brain cell;Brain Neoplasms;cancer cell;Cancer cell line;cancer heterogeneity;cancer type;Cell Communication;Cell Nucleus;Cell Shape;cell type;Cells;chemotherapy;Childhood Glioma;Combined Modality Therapy;Communication;computerized tools;Computing Methodologies;connectome;curative treatments;Data;Development;Diffusion;DNA;DNA Sequence Alteration;drug discovery;Ecosystem;Event;Evolution;experience;Foundations;Generations;Genetic;Genetic Markers;Genetic Transcription;Glioblastoma;Glioma;Heterogeneity;in silico;Infiltration;innovation;insight;Invaded;irradiation;Knock-out;Laboratories;Ligands;Link;Machine Learning;Malignant - descriptor;Malignant Breast Neoplasm;Malignant Neoplasms;Maps;Mediating;Mitochondria;Molecular;Molecular Genetics;multiple omics;Nature;neoplastic cell;Neuronal Differentiation;neuronal tumor;Neurons;Neurosciences;Non-Malignant;Normal Cell;novel therapeutics;Operative Surgical Procedures;Outcome;Oxidative Phosphorylation;Pathway interactions;Patients;pharmacologic;Phase;Phenotype;Phosphoproteins;phosphoproteomics;Phosphotransferases;Precision therapeutics;predict clinical outcome;Primary Brain Neoplasms;Production;progenitor;Prognosis;programs;Proteins;proteogenomics;Proteomics;receptor;reconstruction;Recurrence;Reporting;Resistance;Role;Signal Transduction;single-cell RNA sequencing;spatiotemporal;Squamous cell carcinoma;Squamous Cell Lung Carcinoma;standard of care;stem cells;Synapses;Testing;Therapeutic;therapeutic target;therapy resistant;Time;Tissues;transcriptome sequencing;transcriptomic profiling;transcriptomics;tumor;Tumor Cell Invasion;tumor heterogeneity;tumor microenvironment;tumor progression

PROJECT_TITLE: Dissecting spatiotemporal heterogeneity of glioblastoma evolution under therapy

STUDY_SECTION: NCI

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Clinical Research;Immunotherapy;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Women's Health Research

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: PROJECT NARRATIVE Pregnancy complications affect maternal health and lead to premature delivery or other illnesses in newborns. This application seeks to investigate the mechanisms by which the maternal immune system recognizes and protects the fetus to promote healthy pregnancy outcomes, with the translational goal of decreasing maternal and neonatal morbidity and mortality.

PI_NAMEs: ERICKSON, JOHN J. (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acceleration;Adoptive Transfer;Affect;Allogenic;American;Antibodies;Antigens;Area;Award;B cell differentiation;B cell therapy;B-Cell Activation;B-Cell Antigen Receptor;B-Lymphocyte Subsets;B-Lymphocytes;Binding;Blocking Antibodies;career;career development;CD22 gene;CD8-Positive T-Lymphocytes;Cell Communication;cell type;Cells;Cellular biology;Cellular Immunology;Child;Childhood;Clinical;Complex;CRISPR/Cas technology;Data;Disparate;Effector Cell;effector T cell;embryo/fetus antigen;Equilibrium;experience;experimental study;Faculty;Fellowship;fetal;Fetal Death;Fetal Development;fetal loss;Fetal Tissues;Fetus;Flow Cytometry;FOXP3 gene;Functional impairment;gene-editing approach;Genes;Genetic;genetic manipulation;Genetic Variation;Glycobiology;Glycoproteins;glycosylation;Goals;Hand;healthy pregnancy;Host Defense;Immune;Immune Cell Suppression;Immune system;Immune Tolerance;Immunity;Immunologics;Immunology;Immunosuppression;Impairment;improved;improved outcome;Infant;Infection;innovation;Interleukin-10;interleukin-10 receptor;International;K-Series Research Career Programs;Knowledge;Laboratories;Ligands;Link;loss of function;Lymphocyte;lymphoid organ;male;Maternal Health;maternal immune system;maternal morbidity;Measures;Mediating;Mediator;Mentors;Mentorship;Microchimerism;Modification;mortality;Mothers;mouse model;Mus;Neonatal;neonatal immunity;neonatal morbidity;Neonatal Mortality;neonatal outcome;neonatal sepsis;neonate;Neonatology;Newborn Infant;novel;offspring;Ovalbumin;Pathway interactions;Pediatric Hospitals;Pediatrics;Perinatal;perinatal medicine;Physician Assistants;Physicians;Placenta;Polysaccharides;Positioning Attribute;Pre-Eclampsia;Predisposition;Pregnancy;Pregnancy Complications;pregnancy immunology;Pregnancy Outcome;Pregnant Women;Premature Birth;prevent;Productivity;professor;programs;Proliferating;Property;receptor;receptor binding;receptor expression;Receptor Signaling;Regulation;Regulatory T-Lymphocyte;Reporter;reproductive;Reproductive Immunology;Research;Research Assistant;Research Personnel;Residencies;Resources;response;Role;Scientist;Sialic Acids;sialylation;Signal Transduction;Specificity;stillbirth;Symbiosis;symposium;T-Lymphocyte;Tissues;tool;Training;Transgenic Mice;Transgenic Organisms;translational goal;Universities;Work

PROJECT_TITLE: Maternal B cells enforce fetal tolerance

STUDY_SECTION: AITC

STUDY_SECTION_NAME: Allergy, Immunology, and Transplantation Research Committee[AITC]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: BIRMINGHAM

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: NARRATIVE The proposed study seeks to 1) Investigate whether in-utero exposure to antihypertensive treatment is associated with offspring subclinical cardiovascular disease risk factors (i.e., oxidative stress, inflammation, and arterial stiffness) and 2) Examine whether neighborhood deprivation (i.e., a composite measure of environmental exposures) influences the association of in-utero exposure to hypertensive disorders of pregnancy on offspring vascular outcomes. Successful completion of this study will enhance the candidate’s career development and inform the planning of a future intervention to improve vascular outcomes among children born to mothers with hypertensive disorders of pregnancy. This project leverages an experienced multi-disciplinary mentorship team and is a single-site ancillary study within a larger follow-up study of a chronic hypertension treatment trial funded by the National Heart, Lung, and Blood Institute (NCT02299414).

PI_NAMEs: MARTIN, SAMANTHA L (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: 10 year old;Address;Adult;adverse pregnancy outcome;Age;Alabama;Ancillary Study;Anti-Hypertensive Agents;Area;arterial stiffness;Atherosclerosis;Biometry;Blood Pressure;Blood Vessels;C-reactive protein;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;career;career development;Child;Child Health;Childhood;Chronic;Clinical;clinical care;Clinical Research;cohort;Collaborations;Communities;Crime;Data;Deoxyguanosine;deprivation;Development;Disadvantaged;Disease Outcome;early childhood;Environment;Environmental Exposure;Event;experience;Exposure to;F2-Isoprostanes;fetal;Fetal Growth Retardation;Fetus;follow up assessment;follow-up;Follow-Up Studies;Funding;Future;Goals;Grant;Guidelines;Healthcare Systems;high risk;high risk population;Hypertension;hypertension treatment;improved;Incidence;Inflammation;insight;intergenerational;Intervention;Investigation;Knowledge;late life;Life;Maternal Health;Measures;Mentored Research Scientist Development Award;Mentors;Mentorship;Mothers;multidisciplinary;National Heart, Lung, and Blood Institute;neighborhood disadvantage;Neighborhoods;neonatal outcome;offspring;Organ;Outcome;Oxidative Stress;Parents;Participant;Patients;Physiologic pulse;Positioning Attribute;Poverty;Pre-Eclampsia;Pregnancy;pregnancy disorder;pregnancy hypertension;Pregnant Women;prenatal exposure;Proteinuria;Public Health;Randomized;Research;Research Personnel;retention rate;Risk;Risk Factors;Signal Transduction;Site;skills;social health determinants;Specific qualifier value;standard care;Statistical Data Interpretation;Stress;Subgroup;Testing;therapy development;TNF gene;Training;transmission process;treatment trial;Universities;urinary;Woman;Writing

PROJECT_TITLE: An investigation of the long-term impact of in-utero exposure to mild chronic hypertension and antihypertensive therapy on childhood subclinical cardiovascular risk factors

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-O (O3)]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

ORG_STATE: CA

PHR: Project Narrative The recombination of domains that are structurally and functionally distinct is a fundamental mechanism that drives the expansion of function in protein families. In this proposal, I develop a combined computational-experimental approach to study the interactions between domains that enable them to productively work in tandem to drive the emergence of a new function. Insights from this work will advance basic and applied biology by providing techniques for understanding the acquisition of new function in protein families as well as the design principles that can help to more efficiently generate synthetic proteins through domain fusions.

PI_NAMEs: KOEHL, ANTOINE  (contact)

PROGRAM_OFFICER_NAME: STOKES, KALYNDA K

PROJECT_TERMS: Accounting;Amino Acid Sequence;Architecture;Atrial Natriuretic Factor;atrial natriuretic factor receptor A;Atrial Natriuretic Factor Receptors;Bicarbonates;Binding;Biological;Biological Assay;Biological Process;Biology;Biophysics;Budgets;Carbon;carbonate dehydratase;Cardiovascular system;career;Cell membrane;Cell Surface Receptors;combinatorial;Complement;Complex;Computational Geometry;Coupled;Couples;Coupling;Cyclic GMP;Data;deep learning;design;Development;dimer;Distal;Distant;Engineering;Environment;Enzymes;Evolution;extracellular;Family;Generations;generative models;Genetic Recombination;Genetic study;Goals;Guanylate Cyclase;Homeostasis;Human;insight;Investigation;Knowledge;Learning;Libraries;Ligand Binding;Ligand Binding Domain;Ligands;Link;Machine Learning;machine learning model;Membrane;Mentors;Methods;Modeling;Molecular;Mutagenesis;mutant;Mutation;mutation screening;Natriuretic Peptides;novel;Organism;pathogen;Phase;polypeptide;Positioning Attribute;Process;Production;Productivity;protein complex;Protein Family;Protein Kinase;Proteins;Proton Pump;Proton-Motive Force;Protons;rational design;receptor;Receptor Activation;Receptor Signaling;Reporter;Research;Role;Running;Secondary to;Site;skills;Stimulus;structural biology;Structure;Structure-Activity Relationship;supervised learning;synthetic protein;System;Techniques;Tertiary Protein Structure;Testing;Training;Trees;unsupervised learning;Work

PROJECT_TITLE: Leveraging machine learning and evolution to navigate sequence-function landscapes in multidomain proteins

STUDY_SECTION_NAME: Special Emphasis Panel[ZGM1 TWD-8 (KR)]


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Natural Products;Neurosciences;Pediatric;Pediatric Cancer;Radiation Oncology;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: PEDIATRICS

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: PROJECT NARRATIVE The product of this research effort will be new scientific insight into mechanisms of activity of a novel synthetic oleanane triterpenoid (SOT), known as CDDO-2P-Im or ‘2P-Im’, and a clear demonstration of the capacity of 2P-Im to enhance the response radiation. The success of this effort will define an approach to increasing survival of pediatric patients with a rare cancer, Diffuse Intrinsic Pontine Glioma (DIPG) and other pediatric high-grade gliomas (HGG). The multidisciplinary research team utilizes established preclinical models of DIPG, which remains a significant unmet medical need as less than 1% of patients survive 5 years (the median survival is only 9 months).

PI_NAMEs: LETTERIO, JOHN JAMES (contact)

PROGRAM_OFFICER_NAME: SINGH, ANJU

PROJECT_TERMS: Address;Affect;Attenuated;Biological Assay;Biological Availability;Brain;cancer therapy;CCL2 gene;Cell Line;Cells;chemokine;Child;Childhood Glioma;Chronic;Clone Cells;Data;design;Development;Diet;Diffuse intrinsic pontine glioma;Dose;Genetically Engineered Mouse;glial activation;Glioma;glioma cell line;Growth;high risk;Histone H3.3;Hour;Human;Immunocompetent;Immunotherapy;In Vitro;in vivo;Inflammation;inhibitor;insight;Interdisciplinary Study;Intraperitoneal Injections;Lead;Ligands;Macrophage;Malignant Childhood Neoplasm;Malignant neoplasm of brain;Mediating;Medical;Methionine;Microglia;Modeling;Mole the mammal;Molecular Analysis;Molecular Target;monocyte;mouse model;Mus;Mutation;Myeloid Cell Activation;nano;neurogenesis;New Agents;NF-kappa B;novel;novel therapeutics;oleanane;Oral;Oral Administration;Outcome;patient derived xenograft model;Patients;pediatric patients;Pharmacodynamics;Positioning Attribute;pre-clinical;Pre-Clinical Model;Production;Publishing;Radiation;radiation resistance;radiation response;rare cancer;Recovery;recruit;Recurrence;Refractory;Reporter;Research;response;Rodent;Signal Transduction;STAT3 gene;stem cells;success;Terpenes;Therapeutic;Time;Toxic effect;tumor;tumor microenvironment;Tumor-associated macrophages;United States;Up-Regulation;Xenograft procedure

PROJECT_TITLE: Development of a novel, CNS-penetrant synthetic triterpenoid for pediatric high-grade glioma.

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-P (O2)]


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Genetics;Heart Disease;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative  Deficiency of elastin, the major component of elastic fibers in blood vessel walls, leads to excess vascular smooth muscle cells, which characterizes normal closure of the ductus arteriosus in neonates as well as a number of diseases (e.g., supravalvular aortic stenosis). I recently discovered that the protein sphingosine kinase 1 plays a key role in how defective elastin leads to excess smooth muscle cells. I propose to use human cells and tissue samples as well as mouse models to study underlying mechanisms and thus, delineate concrete steps towards developing novel therapeutic approaches for vascular diseases, especially those afflicting children.

PI_NAMEs: SAITO, JUNICHI  (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: 3-Dimensional;Address;Aorta;Arteries;Attenuated;Binding;Biological Assay;Biology;Blood flow;Blood Vessels;Cell Proliferation;Cells;Child;chromatin immunoprecipitation;Circulation;Clinical;congenital heart abnormality;Data;Development;Dinoprostone;Disease;Ductus Arteriosus;Elastic Fiber;Elasticity;Elastin;Embryo;Enzymes;Failure;gain of function;Genes;Genetic Transcription;Human;induced pluripotent stem cell;inhibitor;Investigation;Link;loss of function mutation;Loss of Heterozygosity;Lung;Malignant Neoplasms;Mediating;monomer;mortality;mouse model;Mus;Mutant Strains Mice;neonate;novel therapeutic intervention;Obstruction;Patent Ductus Arteriosus;Pathway interactions;Patients;Pattern;Pharmaceutical Preparations;pharmacologic;Phase;Phosphorylation;Physiological;Play;Postdoctoral Fellow;postnatal;postnatal human;Proliferating;promoter;Proteins;Role;Signal Transduction;Smooth Muscle Myocytes;Sphingolipids;Sphingosine;sphingosine 1-phosphate;Sphingosine-1-Phosphate Receptor;SPHK1 enzyme;Supravalvular aortic stenosis;Testing;Therapeutic;Tissue Sample;Tissues;transcription factor;Transcriptional Regulation;Transgenic Mice;Tropoelastin;Vascular Diseases;Vascular Smooth Muscle;Williams Syndrome

PROJECT_TITLE: Sphingosine kinase 1 plays a key role in defective elastin-induced arterial hypermuscularization

STUDY_SECTION: MTI

STUDY_SECTION_NAME: NHLBI Mentored Transition to Independence Study Section[MTI (OA)]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: PHILADELPHIA

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Hyperphosphorylation of microtubule (MT) associated protein Tau is tightly correlated with Alzheimer’s disease progression; however, studies of isoform-specific effects of Tau function and dysfunction are largely unexplored. I discovered that phosphorylation differentially regulates adult and fetal Tau isoforms: Tau isoforms have distinct phosphorylation patterns in neurons, and specific phosphorylation sites impact Tau-MT interactions in an isoform-dependent manner. I uniquely propose to use high-throughput pooled optical CRISPR screening and CRISPR prime editing to contrast the effects of Tau phosphorylation (AIM 1) and regulators of Tau-MT interactions (AIM 2) on its function and dysfunction between fetal and adult Tau isoforms, thus providing insight into both loss-of-function and toxic gain-of-function mechanisms in Alzheimer’s disease and other related dementias.

PI_NAMEs: NASERI, NIMA NICK (contact)

PROGRAM_OFFICER_NAME: YANG, AUSTIN JYAN-YU

PROJECT_TERMS: Adopted;Adult;aging brain;Alzheimer's Disease;Alzheimer's disease patient;Alzheimer's disease risk;Area;Automobile Driving;Award;Axon;axon growth;Basic Science;Behavior;Binding;Biochemical;Biophysics;Brain;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Complement;CRISPR screen;Data;Dementia;Development;Disease;Disease Progression;Dissociation;driving force;Embryo;experimental study;fetal;Fetal Development;Functional disorder;Future;gain of function;gene-editing approach;Genetic;genetic risk factor;Genotype;Goals;Heterogeneity;Human;hyperphosphorylated tau;Image;Impairment;In Vitro;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;Induced pluripotent stem cell derived neurons;insight;interest;loss of function;Maps;MAPT gene;Microscope;Microtubule Stabilization;Microtubules;Molecular;mouse model;Mus;Mutation;neonate;Nerve Degeneration;Nervous System Disorder;Neurons;new technology;novel;old mice;Optics;overexpression;Pathologic;Pathology;Pathway interactions;Pattern;Phenotype;Phosphorylation;Phosphorylation Site;Post-Translational Protein Processing;prevent;prime editing;Protein Isoforms;Proteins;Regulation;Research;Role;screening;Site;System;tau aggregation;tau dysfunction;tau function;tau interaction;tau Proteins;tau-1;tau-microtubule interaction;Tauopathies;Technology;Testing;Therapeutic Intervention;tool;Training;Transgenic Mice;Transgenic Organisms;Tubulin;virtual

PROJECT_TITLE: Cellular-molecular regulation of isoform-dependent tau dysfunction in Alzheimer's disease

STUDY_SECTION_NAME: Career Development Facilitating The Transition to Independence Study Section[AGCD-1]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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

ORG_CITY: LITTLE ROCK

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: Project Narrative Both genetic association studies and expression profiling analyses have suggested a role of Piwi-interacting RNAs (piRNAs), a new small noncoding RNA family, in tumorigenesis. The proposed study aims to develop a novel piRNA-based diagnostic method for the early detection of ovarian cancer. This exploratory study will provide proof of concept for future large population-based studies to further investigate the translational role of piRNAs in ovarian cancer.

PI_NAMEs: ZHU, YONG  (contact)

PROGRAM_OFFICER_NAME: PATRIOTIS, CHRISTOS F

PROJECT_TERMS: Acceleration;Age;Applications Grants;biobank;Biological Markers;biomarker development;Blood typing procedure;blood-based biomarker;Cancer Detection;Cancer Patient;cancer type;Cessation of life;Clinical;Code;Cooperative Human Tissue Network;Correlative Study;Data;Death Rate;Detection;Development;Diagnosis;diagnostic biomarker;Diagnostic Procedure;diagnostic tool;Disease;disorder risk;DNA Methylation;DNA Transposable Elements;early detection biomarkers;Early Diagnosis;Epigenetic Process;epigenetic silencing;Ethnic Origin;exosome;Expression Profiling;Family;Feasibility Studies;female reproductive system;Future;Genes;genetic association;Genome Stability;genomic locus;Genomics;Germ Cells;Goals;Gynecologic Oncology Group;Health;Human;improved;innovation;Maintenance;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Malignant Neoplasms;Mammalian Oviducts;Maps;member;Methods;MicroRNAs;Monitor;next generation sequencing;novel;novel diagnostics;Ovarian;Ovarian Diseases;ovarian neoplasm;Ovarian Tissue;overexpression;patient biomarkers;Patients;piRNA;Play;Population Study;potential biomarker;Professional Organizations;Prognosis;Proteins;Publishing;Quantitative Reverse Transcriptase PCR;Radiation therapy;Regulation;Research;response;Risk Assessment;RNA;Role;Sample Size;Sampling;screening;Screening for Ovarian Cancer;Screening procedure;sequencing platform;Serum;Small RNA;Somatic Cell;Survival Rate;Testing;Tissue Sample;Tissues;tool;treatment response;Tumor Debulking;Tumor Tissue;tumorigenesis;Untranslated RNA;validation studies;Woman;women's diagnosis;Women's mortality;Work

PROJECT_TITLE: Explore piRNAs as a novel group of biomarkers for ovarian cancer early detection

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RTRB-S (O1)]


NIH_SPENDING_CATS: Biotechnology;Digestive Diseases;Genetics;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_CITY: PITTSBURGH

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE HBV chronically infects approximately 300 million people worldwide but the currently approved antiviral therapies rarely cure HBV infection. The elimination of HBV persistent cccDNA genome in infected patients is considered to be essential for a cure to hepatitis B, and is the ultimate goal in treatment of this disease. This application aims to discover novel cccDNA inhibitors using an innovative high throughput screening assay, followed by preclinical drug development, which will aid the global effort to eradicate HBV.

PI_NAMEs: GUO, HAITAO  (contact)

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Affect;Affinity;analog;anti-hepatitis B;anti-viral efficacy;Anti-viral Therapy;Automation;Biological Assay;Biological Availability;Cell Culture System;Cell Culture Techniques;Cell Line;Cell model;Cells;Characteristics;Chemicals;Chemistry;Chronic;Chronic Hepatitis B;Circular DNA;Code;Complement;Complex;Core Protein;cytotoxicity;cytotoxicity test;Dependence;design;Detection;Development;Disease;DNA biosynthesis;DNA Maintenance;DNA metabolism;Dose;drug candidate;Drug Kinetics;drug metabolism;druggable target;e Antigens;efficacy testing;Elements;Epigenetic Process;Exclusion;FDA approved;Genetic Transcription;Genome;Goals;Hand;Hepatitis B;Hepatitis B Virus;Hepatocyte;high throughput screening;humanized mouse;In Vitro;in vivo;in vivo evaluation;Infection;inhibitor;innovation;Integration Host Factors;intrahepatic;invention;Knowledge;Label;Lead;lead optimization;Libraries;Life Cycle Stages;Longevity;Luciferases;luminescence;Measurable;Measurement;Measures;Messenger RNA;Metabolic;metabolic profile;miniaturize;Monitor;mouse model;Mus;N-terminal;nanoluciferase;novel;novel therapeutics;Nucleic Acids;Open Reading Frames;Patients;Performance;Persons;Pharmaceutical Preparations;Pharmacology;Phase;Polymerase;posttranscriptional;preclinical development;Preclinical Drug Development;preclinical study;Production;Proteins;prototype;reconstitution;Reporter;Reproducibility;Research;response;RNA;Safety;screening;Serum;Signal Transduction;small molecule libraries;Specificity;stable cell line;Structure-Activity Relationship;System;Tenofovir;Testing;Therapeutic;Transcript;transcriptome;Transgenes;Translating;treatment effect;Validation;Viral;Viral Antigens;viral DNA;Viral Genome;Viral Physiology;Virus;Virus Diseases;Virus Integration;Virus Replication

PROJECT_TITLE: High throughput screening and preclinical development of HBV cccDNA inhibitors

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 SAS-M (S2)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Machine Learning and Artificial Intelligence;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Understanding the social brain, the neural basis of our ability to interact socially, is a fundamental step toward addressing cognitive disorders that have been linked to disruptions in social cognition, such as autism and schizophrenia. Familiarity, the ability to tell if we know someone, and recollection, the detailed recall of past social episodes, are two fundamental building blocks of social cognition; however, it is still unknown how the brain implements these processes, which have different and conflicting computational requirements. Here, I will use recordings from animal subjects, human patients, and machine-learning models to shed light on how the memory system in the brain implements familiarity and recollection, and how these processes are combined to achieve social memory.

PI_NAMEs: POSANI, LORENZO  (contact)

PROGRAM_OFFICER_NAME: VAN'T VEER, ASHLEE VICTORIA

PROJECT_TERMS: Address;Age;Animals;Architecture;Area;artificial neural network;autism spectrum disorder;Brain;Categories;Cells;Classification;Code;Cognition;Cognition Disorders;Collaborations;Collection;Complex;computational neuroscience;Computer Models;Data;Data Analyses;Data Set;design;Dimensions;entorhinal cortex;experience;Experimental Designs;experimental study;Exposure to;Face;Familiarity;Fostering;Future;Gender;Geometry;high dimensionality;Hippocampus;Human;human subject;improved;Individual;Inherited;Knowledge;Lateral;Learning;Life;Link;machine learning model;Medial;Memory;Mental disorders;Mentorship;Meta-Analysis;Modeling;multisensory;Mus;Neocortex;neural;Neural Network Simulation;neuromechanism;Neurons;novel;open source;Patients;Pattern;Performance;Phase;Positioning Attribute;Process;Property;Reporting;Rodent;Role;Schizophrenia;scientific hub;Shapes;social;Social Behavior;social cognition;Social Identification;Social Interaction;Specificity;Standardization;Stimulus;Structure;synergism;System;Testing;Training;Universities;Work

PROJECT_TITLE: Investigating the neural mechanisms of social memory in the hippocampal-cortical network

STUDY_SECTION_NAME: Special Emphasis Panel[ZMH1 ERB-M (05)]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Prevention

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: Project Narrative The abnormal deposition of bone-like mineral in the valve and vasculature, also known as vascular calcification (VC), increases with age, vascular and valvular disease, diabetes and chronic kidney disease (CKD). Calcification of these organs leads to loss of compliance, stiffening and increased tendency to rupture, contributing to declining cardiovascular function and heart failure. There are no drug therapies for VC. The proposed research provides a foundation for future translational and clinical studies aimed at identifying effective biomarkers and targets, as well as developing therapeutics to prevent and/or treat VC.

PI_NAMEs: GIACHELLI, CECILIA M (contact)

PROGRAM_OFFICER_NAME: STABLEY, JOHN N

PROJECT_TERMS: Age;Animal Model;Biological Markers;biomarker identification;Blood Vessels;bone;calcification;calcium phosphate;cardiac vasculature;Cardiovascular Physiology;Cell Culture Techniques;cell growth regulation;cell type;Chronic Kidney Failure;Clinical Research;Coronary Arteriosclerosis;Deposition;Diabetes Mellitus;Disease;experimental study;Foundations;Future;Genetic;Genetic Diseases;Goals;Health;Heart failure;Heart Valves;hemodynamics;high risk;Human;improved;Knowledge;Minerals;Molecular;Organ;Organoids;Pathway interactions;pharmacologic;Pharmacotherapy;Play;prevent;Process;Research;Risk Factors;Role;Rupture;Salts;Signal Pathway;targeted treatment;Therapeutic;therapeutic development;therapeutic target;translational study;Vascular calcification;Vascular Diseases

PROJECT_TITLE: Molecular and Cellular Regulation of Vascular Calcification

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-I (O1)]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Women's Health Research

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARATIVE Chronically elevated sympathetic tone in heart failure leads to b-adrenergic receptor desensitization, calcium overload, and increased risk of ventricular arrhythmia. Heart failure incidence and outcomes are strongly sex dependent; females have a lower incidence of arrhythmia than men, yet the mechanistic differences are not fully understood. By combining new whole-heart, cellular, and sub-cellular imaging approaches, this project aims to uncover novel mechanisms that underlie sex differences in b-adrenergic signaling and may promote sex- dependent outcomes in heart failure, with potential therapeutic implications.

PI_NAMEs: CALDWELL, JESSICA  (contact)

PROGRAM_OFFICER_NAME: WEBB, STEPHANIE JOHNSON

PROJECT_TERMS: Action Potentials;Address;Adenylate Cyclase;Adrenergic Agents;Adrenergic beta-Antagonists;Adult;Advisory Committees;Affect;Anti-Arrhythmia Agents;aorta constriction;Arrhythmia;Award;base;beta-adrenergic receptor;Biochemical;Biological Assay;Calcium;Cardiac;Cardiomyopathies;Cardiovascular Physiology;Cause of Death;Cessation of life;Chronic;Collaborations;Coupling;Cyclic AMP;Cyclic AMP Receptor Protein;Cyclic AMP Receptors;Cyclic AMP-Dependent Protein Kinases;Data;desensitization;effective therapy;Electrophysiology (science);Environment;experience;experimental study;extracellular;Faculty;Female;Fluorescence Resonance Energy Transfer;Functional disorder;functional outcomes;Funding;Gender;Gene Expression;Generations;Goals;Growth;Heart;Heart failure;heart failure with reduced ejection fraction;heart imaging;Heterogeneity;imaging approach;imaging system;Impairment;Incidence;insight;Lead;Ligation;male;Maps;men;Mentors;Modeling;multidisciplinary;Mus;Muscle Cells;nanoscale;novel;novel therapeutic intervention;Optics;Outcome;Output;Pathway interactions;Patients;Phase;phosphoric diester hydrolase;Positioning Attribute;preservation;prevent;programs;Publishing;Receptor Activation;regional difference;Reporter;Research;response;Risk;Rodent Model;Role;sex;Sex Differences;Signal Pathway;Signal Transduction;skills;superresolution microscopy;Survival Rate;System;Testing;Therapeutic;Time;Training;training opportunity;Ventricular Arrhythmia;Woman;women versus men

PROJECT_TITLE: Sex-dependent cardiac cyclic-AMP signaling and arrhythmias in the failing heart

STUDY_SECTION_NAME: Special Emphasis Panel[ZHL1 CSR-G (O1)]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Genetics;Human Genome;Social Determinants of Health

ORG_CITY: STANFORD

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Using an innovative multi-stakeholder approach, this study will contribute essential and timely data, new methods, and ethical analyses to first investigate stakeholders’ (i.e., social and behavioral genomics (SBG) researchers, journal editors, journalists, members of industry, parents, and K-12 educators) roles in the conduct and translation of SBG and their perspectives on SBG’s downstream harms/benefits. It will then determine stakeholders’ roles in producing, mitigating, and/or promoting the downstream harms benefits of SBG for the purpose of locating social responsibility. Finally, the proposed research will identify – through multistakeholder engagement – strategies for mitigating the harms and promoting the benefits of SBG.

PI_NAMEs: MARTSCHENKO, DAPHNE OLUWASEUN (contact)

PROGRAM_OFFICER_NAME: JOSE, SHEETHAL

PROJECT_TERMS: Accountability;Accounting;Address;Adopted;Advisory Committees;Affect;Aggressive behavior;Agreement;Behavioral;behavioral genomics;California;care systems;career;career development;Characteristics;clinical care;common rule;Communication;Curiosities;Data;design;Development Plans;Education;education research;Educational Models;Ethical Analysis;ethical, legal, and social implication;Ethics;federal policy;Foundations;Genetic;genetic discrimination;genetic resource;Genetic study;genetic testing;genome-wide;genomic data;Genomics;Grant;Human Genetics;improved;Incentives;Income;Individual;Industry;innovation;Institution;Institutional Review Boards;Intelligence;Intelligence Tests;interest;Interview;Journals;K-12 Faculty;Learning Disabilities;Left;Los Angeles;mathematical ability;member;Mentors;Methods;Molecular;novel;Outcome;Parents;Participant;Policies;Policy Developments;policy implication;prevent;Publications;Publishing;Research;Research Personnel;Risk;Role;San Francisco;Science;Secure;Series;Shapes;social;social disparities;social genomics;social implication;Social Marketing;Social Policies;Social Responsibility;Social Sciences;Social Work;Societies;Structure;Technology;theories;Time;tool;Training;trait;Translating;translational genomics;Translational Research;Translations;Universities;Voice

PROJECT_TITLE: A Multi-stakeholder Approach to the ELSI of Social and Behavioral Genomics: Investigating the Field's Downstream Implications to Mitigate Harms, Promote Benefits, and Locate Social Responsibility

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 SEIR-S (80)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Patient Safety;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Racial, ethnic, and socioeconomic disparities in type 1 diabetes management and outcomes are poorly defined. Using data from a large administrative claims database, this project will rigorously characterize inequities in the use of diabetes technology, the attainment of glycemic control, and the burden of major morbidity and mortality among children and adults with type 1 diabetes. These data will identify critical gaps in the management of type 1 diabetes and inform efforts to reduce social disparities in the population.

PI_NAMEs: FANG, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, JEAN M

PROJECT_TERMS: access disparities;Acute;Address;Adult;Affect;Algorithms;Area;Award;Cardiovascular system;career;career development;Caring;Center for Translational Science Activities;Child;Childhood diabetes;Chronic Kidney Failure;Clinical;clinical risk;cohort;Collaborations;Complications of Diabetes Mellitus;Continuous Glucose Monitor;Coronary heart disease;Data;data warehouse;Databases;Devices;diabetes control;diabetes management;Diabetes Mellitus;Disease Progression;Disparity;Disparity population;disparity reduction;Doctor of Philosophy;Electronic Health Record;Emergency Situation;Epidemiology;ethnic disparity;ethnic minority;Ethnic Origin;Event;experience;Five-Year Plans;Formulation;Fostering;glycemic control;Goals;Health;health difference;health equity;health inequalities;Health Policy;Heart failure;Hyperglycemia;Hypoglycemia;improved;Income;Individual;Inequity;Insulin;Insulin Infusion Systems;Insulin-Dependent Diabetes Mellitus;International;Life Cycle Stages;Life Expectancy;lifetime risk;Measures;Medicaid;Mentored Research Scientist Development Award;Mentors;Mentorship;Metabolic;metabolic rate;Methods;Microvascular Dysfunction;minority patient;Modeling;models and simulation;Morbidity - disease rate;mortality;Neuropathy;new technology;Non-Insulin-Dependent Diabetes Mellitus;Outcome;Patients;Persons;Population;population based;Population Study;Premature Mortality;prevent;professor;Prognosis;programs;prospective;Public Health Informatics;Public Health Schools;Publishing;Race;racial disparity;racial minority;Recommendation;Research;Research Personnel;Research Proposals;Retinal Diseases;Risk;risk prediction;Scientist;simulation;skills;social;social disparities;social health determinants;socioeconomic disparity;socioeconomics;Specialist;Stroke;study population;Subgroup;Technology;Training;Translational Research;treatment disparity;trend;Uninsured

PROJECT_TITLE: Disparities in the management and prognosis of type 1 diabetes

STUDY_SECTION: DDK

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


NIH_SPENDING_CATS: Lung;Pulmonary Fibrosis

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project narrative The periphery-to-center progression of tissue fibrosis is the hallmark of Idiopathic pulmonary fibrosis (IPF), of which the cellular and molecular basis is poorly understood. My preliminary data reveal that a rarely characterized population of fibroblasts in the subpleural region contribute to fibrogenesis. This proposal will investigate the characteristics and functions of subpleural fibroblasts in the setting of progressive fibrosis.

PI_NAMEs: XU, LE  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA-PINTUCCI, MARISOL

PROJECT_TERMS: Address;alveolar epithelium;Biological;career;Cells;Characteristics;chemokine;Chronic;Cicatrix;Cues;Cyst;cytokine;Data;Deposition;Development;Diagnosis;Discipline;Disease;Early Diagnosis;Early treatment;epigenomics;Epithelial Cells;epithelial injury;Epithelium;Etiology;Exhibits;Extracellular Matrix Proteins;Fibroblasts;fibrogenesis;Fibrosis;fibrotic lung;fibrotic lung disease;frontier;genetic approach;Goals;Human;idiopathic pulmonary fibrosis;Immunology;in vivo;infancy;Inflammation;injured;insight;interstitial;Interstitial Lung Diseases;Knowledge;Ligands;Lung;lung injury;Macrophage;Mechanics;Mentors;Mesenchymal;Mesothelial Cell;Mesothelium;Molecular;monocyte;mortality;mouse model;multimodality;Myeloid Cells;Myofibroblast;neutrophil;novel;Pathologic;Pleural;Pneumonectomy;Population;Process;Productivity;Profibrotic signal;progenitor;Pulmonary Fibrosis;receptor;recruit;Research Personnel;Role;Signal Transduction;single cell sequencing;single cell technology;Source;synergism;Technology;Testing;Time;Tissues;Training;transcription factor;TWIST1 gene;Validation;WT1 gene;Zea

PROJECT_TITLE: Frontiers at the edge: Subpleural fibroblasts orchestrate pulmonary fibrosis progression


ADMINISTERING_IC: AT

ED_INST_TYPE: SCH OF HOME ECON/HUMAN ECOLOGY

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Mental Health;Pediatric;Prevention

ORG_CITY: FORT COLLINS

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: Project Narrative The proposed research is highly relevant to public health because identifying feasible, acceptable, and effective interventions offers the possibility of reducing depression, anxiety, and stress for students at U.S. colleges and universities, the majority of whom experience mental health problems but the minority of whom who receive adequate mental health support. By studying the extent to which a multi-modal supplement boosts effects for a mindfulness-based intervention (and systematically comparing both to an active health education control program) to reduce depression, anxiety, and stress, the proposed research is highly consistent with NCCIH’s mission to rigorously investigate complementary and integrative health interventions and their roles in improving health.

PI_NAMEs: LUCAS-THOMPSON, RACHEL  (contact)

PROGRAM_OFFICER_NAME: JEAN-FRANCOIS, BEDA

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Adolescent;Adult;Anxiety;Area;arm;Arousal;Behavior;Clinical;college;combat;Competence;Complementary Health;Data;design;effective intervention;Effectiveness;efficacy evaluation;efficacy trial;Elements;emotion regulation;Enrollment;evidence base;experience;Feasibility Studies;Funding;Future;Health;Health Benefit;Health education;high risk population;implementation intervention;improved;Individual;Integrative Medicine;Intervention;intervention effect;Learning;learning strategy;Left;Life;Literature;Longterm Follow-up;Mental Depression;Mental Health;Mental Health Services;Meta-Analysis;Methods;mindfulness;mindfulness intervention;Mindfulness Training;Minority;Mission;multi-site trial;multimodality;National Center for Complementary and Integrative Health;Persons;Population;Process;programs;Protocols documentation;psychological distress;Public Health;Randomized;Randomized, Controlled Trials;recruit;Regulation;Research;Resources;Role;Science;Series;Signal Transduction;Site;skills;Stress;stress management;stress reduction;Students;supplemental instruction;Symptoms;Target Populations;Technology;Testing;Time;tool;Training;Treatment Efficacy;Universities;university student;Work;Youth

PROJECT_TITLE: Testing a Mindfulness-Based Intervention with a Multi-Modal Adaptive Supplement for Stress-Related Problems in College Students

STUDY_SECTION_NAME: Special Emphasis Panel[ZAT1 MH (05)]


NIH_SPENDING_CATS: Lymphatic Research;Nutrition;Obesity

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Obesity is a serious, and costly chronic disease in the United States. Emerging evidence points to a critical pathogenic link between lymphatic vessel dysfunction and obesity. I will investigate the impairments in lymphatic endothelial Ca2+ signaling in obesity and provide strategies to protect lymphatic barrier function and in turn, improve body weight regulation in obesity.

PI_NAMEs: CHEN, YEN-LIN  (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Adipose tissue;Adult;Agonist;American;Award;Back;Blood Circulation;Blood Vessels;Body fat;Body Weight;Cardiovascular Diseases;career development;Cations;Chronic Disease;cost;Data;Development;Diabetes Mellitus;Electrophysiology (science);Environment;Extravasation;feeding;Functional disorder;Hand;Health;High Fat Diet;Hydrostatic Pressure;Image;Impairment;improved;Inflammation;Intercellular Fluid;Ion Channel;Knock-out;Knockout Mice;Link;Liposomes;LoxP-flanked allele;Lymph;Lymphangiography;Lymphatic;lymphatic dysfunction;Lymphatic Endothelial Cells;Lymphatic Endothelium;Lymphatic function;lymphatic valve;lymphatic vessel;Measurement;Mentors;Mesentery;mortality;Mus;Muscle Cells;novel;Obesity;Pathogenicity;Pathway interactions;Peripheral;Permeability;Piezo 1 ion channel;Postdoctoral Fellow;prevent;Protein Analysis;Proteins;receptor;Regulation;Research;Research Personnel;Risk Factors;Role;shear stress;Signal Pathway;Signal Transduction;Stroke;Tamoxifen;Testing;Tissues;Training;United States;United States National Institutes of Health;Vanilloid;Weight;Weight Gain;Weight maintenance regimen

PROJECT_TITLE: Lymphatic Endothelial Piezo1-TRPV4 Channel Signaling in Obesity


NIH_SPENDING_CATS: Biotechnology

ORG_CITY: PASADENA

ORG_NAME: CALIFORNIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE. Biological nitrogen fixation by nitrogenase sustains life on Earth through the production of metabolically available nitrogen for incorporation into essential biomolecules. The proposed research targets select aerobic and anaerobic diazotrophic bacteria with emerging cryoET methodologies to answer key questions about the nitrogenase enzymatic mechanism in the cellular context. Examining the structure function relationships of nitrogenase in this context will inform on other metalloenzyme mechanisms enzymes relevant to human health, and on the design of synthetic systems for the sustainable production of ammonia for agriculture.

PI_NAMEs: WARMACK, REBECCAH  (contact)

PROJECT_TERMS: Advisory Committees;Aerobic;Aerobic Bacteria;Agriculture;Ammonia;Anaerobic Bacteria;Architecture;Award;Azotobacter vinelandii;Bacteria;Binding;Biochemical;Biochemical Reaction;Biological;career;Catalogs;Catalytic Domain;cell growth regulation;Cell membrane;Cell Separation;Cells;Chemistry;Classification;Complex;Coupled;Cryo-electron tomography;Cryoelectron Microscopy;cryogenics;Crystallography;Cytolysis;Data;deprivation;design;Electron Microscopy;electron tomography;Environment;enzyme mechanism;Enzymes;experimental study;Fellowship;Foundations;Funding;Genes;genetic manipulation;genome editing;Goals;Growth;Health;Human;In Situ;In Vitro;in vivo;innovation;insight;Investigation;Ions;Iron;knock-down;Life;Light;light microscopy;Mass Spectrum Analysis;Membrane;Metabolic;Metabolism;metalloenzyme;Metalloproteins;Methodology;Molecular;Molybdoferredoxin;Multienzyme Complexes;new technology;Nif Genes;Nitrogen;Nitrogen Fixation;Nitrogenase;novel;Organism;Oxidoreductase;Oxygen;paired helical filament;particle;Pathway interactions;Phase;Planet Earth;Population;Postdoctoral Fellow;pressure;Process;Production;programs;Prokaryotic Cells;protein complex;protein structure;Proteins;Proteomics;reconstruction;repaired;Research;Resolution;response;Role;Seminal;skills;Soil;spectroscopic survey;Stress;Structure;Structure-Activity Relationship;System;Targeted Research;Techniques;Temperature;tomography;Training;United States National Institutes of Health;Vesicle;Wit;Work

PROJECT_TITLE: In situ mechanisms of biological nitrogen fixation


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Genetics

ORG_CITY: CAMBRIDGE

ORG_NAME: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES

ORG_STATE: MA

PHR: Project Narrative Germ cells must maintain their identity for the entirety of a species reproductive lifespan, a task that can last more than forty years in humans. This unique challenge raises the question: What underlying molecular processes govern germ cell identity and protect germ cells from reprogramming towards a somatic cell fate? Using the fruit fly Drosophila melanogaster, I will answer this fundamental question by (i) characterizing the germline transcriptional program and probing cell autonomous vs nonautonomous mechanisms for transcriptional activation (ii) identifying regulatory factors that are instructive for germline specification, (iii) uncovering how the conserved translational repressor Nanos protects germ cell fate by repressing somatic transcription in germlines from flies to humans.

PI_NAMEs: GRILL, SHERILYN ANN (contact)

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: active control;Address;ATAC-seq;Binding;Binding Sites;Biochemistry;Bioinformatics;Biological Assay;Biological Models;Biology;Cell Reprogramming;cell type;Cells;Chromatin;Code;Cues;Development;Drosophila genus;Drosophila melanogaster;Embryo;Embryonic Development;experimental study;Face;Fertility;fly;gain of function;Gene Activation;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene regulatory network;Genes;Genetic;Genetic Markers;Genetic Transcription;Germ Cells;Germ Lines;Goals;Health;Human;in vivo;interest;life span;loss of function;Mediating;Methods;Modeling;Molecular;Molecular Biology;Mus;mutant;Mutation;nano;neuronal cell body;next generation;novel;Organism;Play;premature;prevent;Process;programs;Reporter;Repression;reproductive;Research;RNA;RNA-Binding Proteins;Role;Signal Transduction;single-cell RNA sequencing;Somatic Cell;Specific qualifier value;Structure of primordial sex cell;System;Testing;Time;Tissues;Totipotency;Totipotent;Training;Trans-Activators;transcription factor;Transcriptional Activation;Translations;Validation;Work

PROJECT_TITLE: Uncovering the Mechanisms that Promote and Maintain Germ Cell Identity

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Developmental Biology Study Section[CHHD-C]


NIH_SPENDING_CATS: Anorexia;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Eating Disorders;Mental Health;Mental Illness;Nutrition;Serious Mental Illness

ORG_CITY: TULSA

ORG_NAME: LAUREATE INSTITUTE FOR BRAIN RESEARCH

ORG_STATE: OK

PHR: PROJECT NARRATIVE Anorexia nervosa (AN) is a deadly psychiatric disorder and yet current treatments for AN show only moderate efficacy. Interoceptive processing dysfunctions (i.e., how the brain receives and processes body afferents), contribute to body image disturbance (BID), a core feature of AN associated with poor treatment outcomes. The proposed project works to establish (1) how interoceptive processing dysfunctions contribute to BID and (2) how the use of a nonpharmacological experimental therapeutic targeting interoceptive processing affects BID with the larger goal of improving treatment for BID in AN.

PI_NAMEs: CHOQUETTE, EMILY  (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: active comparator;Acute;Address;Affect;Affective;Age;Anorexia Nervosa;Appearance;arm;Attenuated;Auditory;Behavioral;Behavioral Assay;Biological Assay;body dissatisfaction;Body Image;Body mass index;Brain;brain research;career;Cessation of life;Characteristics;Clinic;Clinical;Clinical Trials;Cognitive;cognitive enhancement;Cognitive Therapy;cognitive training;Complex;Death Rate;design;Development;Diagnostic;Eating Disorders;Educational Intervention;experience;experimental group;Functional disorder;Future;Goals;Group Practice;Growth;Home;Hospitalization;Hospitals;improved;indexing;Individual;Inpatients;Institution;Interoception;Intervention;Investigational Therapies;K-Series Research Career Programs;Knowledge;Link;Location;Measures;Mediation;Mediator;Mental disorders;mental representation;Mentors;Mentorship;Modeling;multimodality;Nonpharmacologic Therapy;novel;Outcome;Participant;patient oriented;Patient Self-Report;Photography;post intervention;power analysis;primary endpoint;Process;programs;Psychophysiology;Psychotherapy;Qualifying;Randomized;Recording of previous events;recruit;Relapse;Research;research facility;Research Methodology;Research Personnel;Role;Scientist;Signal Transduction;standard of care;Standardization;statistics;Symptoms;Tactile;Techniques;Testing;therapeutic target;therapy development;Training;Training Activity;trait;Treatment outcome;United States;vestibular system;Visual;visual stimulus;Weight;Woman;Work

PROJECT_TITLE: Interoceptive mechanisms of body image disturbance in anorexia nervosa

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-P (02)]


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

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Alzheimer’s disease patients may have offline processing deficits that contribute to memory issues. I will use a mouse model of Alzheimer’s disease to determine cortical network impairments during the offline processing in sleep and to modulate neuron and glia networks during sleep to improve memory retention. The completion of this preclinical project may lead to the innovation of novel diagnostics and treatment options for the millions of Americans that suffer from Alzheimer’s disease.

PI_NAMEs: LINES, JUSTIN  (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: 3-Dimensional;abeta accumulation;abeta oligomer;Acoustic Stimulation;Adult;Affect;Age;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease therapeutic;Alzheimer's disease therapy;American;Animal Disease Models;Animal Experimentation;Animal Model;Animals;area striata;Astrocytes;awake;Behavior;Behavioral;Brain;Calcium;calcium indicator;career;Cells;Cues;Dementia;Deposition;design;Diagnosis;discrimination task;Disease;Disease Progression;Doctor of Philosophy;Early Diagnosis;Elderly;Electrocorticogram;Electromyography;Electrophysiology (science);experimental study;Exposure to;Frequencies;Functional disorder;Funding;Goals;Health;Holography;Human;Image;Impaired cognition;Impairment;improved;improvement on sleep;in vivo;Individual;information processing;innovation;Institution;Learning;Light;long term memory;Measures;melanopsin;Memory;memory acquisition;memory consolidation;Memory impairment;memory process;memory retention;Methods;mild cognitive impairment;Monitor;mouse model;Mus;Nervous System Disorder;Neurofibrillary Tangles;Neuroglia;Neurons;novel;novel diagnostics;novel therapeutics;Opsin;Optics;optogenetics;Patients;Pattern;Performance;post-doctoral training;pre-clinical;pre-clinical research;Principal Investigator;redshift;Research;Science;Scientist;Sensory;Sleep;sleep behavior;Sleep Fragmentations;Slow-Wave Sleep;Task Performances;tau aggregation;tau Proteins;Tauopathies;Techniques;Testing;theories;Training;two photon microscopy;United States National Institutes of Health;Viral;visual discrimination

PROJECT_TITLE: Holographic activation of ensemble activity during sleep in a mouse model of Alzheimer's disease


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Coronaviruses;Coronaviruses Therapeutics and Interventions;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

PHR: PROJECT NARRATIVE: The emergence of immune-evasive SARS-CoV-2 variants poses an urgent threat to public health, necessitating the development of updated vaccines, but the optimal boosting strategy in previously vaccinated individuals remains unknown. The proposed research will employ controlled immunization studies in a humanized mouse model to elucidate the impact and molecular basis of immune imprinting due to previous vaccination on subsequent humoral responses to viral variants. Understanding imprinting responses to viral variant antigens will inform novel vaccine strategies for SARS-CoV-2 and other antigenically variable pathogens.

PI_NAMEs: BOWEN, ANTHONY  (contact)

PROGRAM_OFFICER_NAME: ARNOLD, MICHELLE MARIE

PROJECT_TERMS: 2019-nCoV;Animal Model;Antibodies;Antibody Repertoire;Antibody Response;Antibody titer measurement;Antigenic Variation;Antigens;B cell repertoire;B-Lymphocytes;Binding;Bioinformatics;Biological Assay;Biomedical Research;booster vaccine;breakthrough infection;career;Cessation of life;Communicable Diseases;COVID-19 vaccination;cross immunity;cross reactivity;Cryoelectron Microscopy;Data;Development;Doctor of Philosophy;Dose;Effectiveness;Environment;environmental enrichment for laboratory animals;Epidemic;Epitopes;Evolution;Exposure to;Future;Genes;Germ Lines;Goals;Human;humanized mouse;Humoral Immunities;IGH@ gene cluster;Immune;Immune Evasion;Immune response;Immune system;Immunization;Immunize;immunogenicity;Immunoglobulin Somatic Hypermutation;Immunoglobulins;Immunologics;Immunology;imprint;improved;Infection;Influenza A virus;innovation;insight;Junior Physician;Knowledge;Laboratories;Length;Light;Medical center;Medicine;Memory B-Lymphocyte;Mentors;Messenger RNA;Microbiology;Molecular;Monoclonal Antibodies;mouse model;multidisciplinary;Mus;neutralizing antibody;novel;novel strategies;novel therapeutics;novel vaccines;pathogen;Patient Care;Pattern;Pfizer-BioNTech COVID-19 vaccine;Physicians;Placebos;Play;Positioning Attribute;Production;Proteins;Public Health;receptor binding;Research;response;RNA vaccination;RNA vaccine;Role;Sarbecovirus;SARS-CoV-2 antigen;SARS-CoV-2 B.1.1.529;SARS-CoV-2 B.1.617.2;SARS-CoV-2 immunity;SARS-CoV-2 spike protein;SARS-CoV-2 variant;Scientist;Serum;single cell sequencing;Sorting;Splenocyte;structural biology;Structure;Surface Plasmon Resonance;Techniques;Testing;Therapeutic;Therapeutic Monoclonal Antibodies;Training;Transfection;Universities;Update;Vaccinated;Vaccination;vaccination strategy;Vaccine Design;vaccine strategy;Vaccinee;Vaccines;Variant;Vertebral column;Vesicular stomatitis Indiana virus;Viral;virology;Virus;Work

PROJECT_TITLE: Elucidating the impact of immune imprinting on SARS-CoV-2 variant vaccination strategies using a humanized mouse model


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Diabetes;Dissemination and Implementation Research;Patient Safety

PHR: PROJECT NARRATIVE  Hospitalized patients with diabetes face increased risks of morbidity and mortality due to high and low glycemic excursions during acute illness. The current standard of administering multiple daily injection insulin therapy to manage diabetes in the hospital is often inadequate and results in unacceptably high rates of both hyperglycemia and iatrogenic hypoglycemia. This proposal aims to examine and optimize the use of automated insulin delivery systems in the hospital by evaluating their effectiveness, identifying barriers and facilitators to their use in the hospital, and developing implementation strategies to improve glycemic control for hospitalized patients with diabetes.

PI_NAMEs: HUGHES, MICHAEL SAMUEL (contact)

PROGRAM_OFFICER_NAME: THORNTON, PAMELA L

PROJECT_TERMS: Acceleration;Acute;Admission activity;Adoption;Adult;Algorithms;arm;Automation;Blinded;Blood Glucose;career;Caring;Cessation of life;Classification;Clinical;Clinical Informatics;Collaborations;Consumption;Continuous Glucose Monitor;COVID-19 pandemic;Data;Data Set;Development;Devices;diabetes management;Diabetes Mellitus;Effectiveness;effectiveness evaluation;Endocrinology;Enrollment;evidence base;Evolution;experience;Face;FDA approved;Fingers;Future;Gerontology;Glucose;glucose monitor;glycemic control;Goals;Grant;Guidelines;high risk;Home;Hospital Design;Hospital Personnel;Hospitalization;Hospitals;Hour;Hyperglycemia;Hypoglycemia;Iatrogenesis;implementation science;implementation strategy;improved;improved outcome;Individual;Infrastructure;Injection of therapeutic agent;Injections;Inpatients;insight;instructor;Insulin;Insulin Infusion Systems;Insulin-Dependent Diabetes Mellitus;Interview;Manuals;Maps;Marketing;Master of Science;Medical;Medical Care Team;Medicine;Mentors;Mentorship;Metabolism;Methods;Morbidity - disease rate;mortality;Non-Insulin-Dependent Diabetes Mellitus;Observational Study;Operative Surgical Procedures;Outcome;Outpatients;Patient Care;Patients;personal protective equipment;Persons;Physicians;Pilot Projects;pilot trial;Positioning Attribute;pre-pandemic;Process;programs;prospective;Publishing;Pump;Qualifying;Quality of life;Readiness;Recommendation;Research;Research Methodology;Research Personnel;Risk;Scientist;skills;Structure;System;Techniques;Technology;Testing;Time;Training;trend;Universities

PROJECT_TITLE: In-hospital use of Automated Insulin Delivery (AID): Current state and future potential


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_DEPT: BIOLOGY

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

PHR: Neurons rely on mechanisms of RNA-localization and local-translation for many aspects of their biology such as axonal growth and synaptic plasticity. RNA binding proteins are essential for regulating these processes and are frequently mutated in neurodegenerative disease. This project aims to understand how the molecular interplay between RNA binding proteins control activity- dependent local-translation, to enhance fundamental knowledge about the molecular underpinnings of learning and memory.

PI_NAMEs: DORON-MANDEL, ELLA  (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Adopted;Affect;Architecture;Automobile Driving;axon growth;Behavior;beta Actin;Binding;Binding Proteins;Biological Models;Biology;Brain-Derived Neurotrophic Factor;candidate identification;Case Study;Cells;Code;Complement;Complex;Dendrites;Dissociation;Endowment;experimental study;follow-up;Follow-Up Studies;functional outcomes;Genes;Goals;Hippocampus;holistic approach;Image;Knowledge;Lead;Learning;mammalian genome;Measures;Memory;Mentors;Messenger RNA;Methodology;Modeling;Molecular;Mutate;Nature;neural;Neurodegenerative Disorders;Neuronal Plasticity;Neurons;novel;novel strategies;Nuclear Export;Outcome;Phase;posttranscriptional;Process;protein function;protein protein interaction;Proteins;Regulation;Resolution;Resources;response;RNA;RNA Transport;RNA-Binding Proteins;RNA-Protein Interaction;Role;Science;skills;stem;Stimulus;Study models;Synapses;Synaptic plasticity;System;Time;tool;Transcript;Translations

PROJECT_TITLE: How dynamic interactions of RNA binding proteins control activity-dependent translation in neurons

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Infectious Diseases;Machine Learning and Artificial Intelligence

ORG_CITY: KANSAS CITY

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: UNIVERSITY OF MISSOURI KANSAS CITY

ORG_STATE: MO

PHR: Project Narrative Antibiotic resistant bacterial pathogens have become a leading cause of death globally and doctors are left with few remaining treatment options. To overcome this emerging threat, new antibiotics need to be developed, but few are currently in the clinical pipeline. The aim of this proposal is to better understand the function and therapeutic potential of a rare class of macrocyclic antimicrobial peptides with beta-hairpin secondary structure using high-throughput screens followed by biochemical, computational, and mechanistic analyses.

PI_NAMEs: RANDALL, JUSTIN ROY (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Amino Acid Sequence;analog;Anti-Bacterial Agents;anti-microbial peptide;Antibiotic Resistance;Antibiotics;antimicrobial;Antimicrobial Cationic Peptides;Antimicrobial Resistance;antimicrobial resistant infection;Attention;Bacteria;Bacterial Antibiotic Resistance;Bacterial Infections;Bacterial Model;Binding;Biochemical;Biological Assay;Bypass;career;career development;Cause of Death;Cell membrane;Cells;Clinical;clinically relevant;Collaborations;combat;Cyclization;Data;Data Set;Development;disulfide bond;drug resistant pathogen;Evaluation;fighting;flexibility;Gene Modified;Genetic;global health;Goals;high throughput screening;improved;In Vitro;in vivo;Infection;Lead;Left;Lipids;Lipopolysaccharides;Liposomes;machine learning algorithm;Mammalian Cell;Mass Spectrum Analysis;Measures;Medical;Membrane;membrane activity;Methods;Modeling;Modification;Mutation;Nosocomial Infections;novel;pathogenic bacteria;Penetration;Peptides;Periodicity;Phase;Phospholipids;Positioning Attribute;prevent;Principal Investigator;protegrin PG-1;Refractory;Research;Resistance;scaffold;Scanning;screening;Site;small molecule;Specificity;Structure;Techniques;tenure track;Therapeutic;therapeutic development;Therapeutic Uses;Toxic effect;Training;training data;trait;ultraviolet;Variant;viral pandemic

PROJECT_TITLE: Investigating beta-hairpin antimicrobial peptide membrane activity and toxicity.

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases Research Study Section[MID]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Asthma;Chronic Obstructive Pulmonary Disease;Climate-Related Exposures and Conditions;Clinical Research;Lung;Prevention

ORG_CITY: BOSTON

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: PROJECT NARRATIVE In order to protect public health from a rapidly changing climate through preventive patient care and public health policies, it is essential for the medical community to understand the impact of temperature, precipitation, and its extremes on respiratory health, particularly in those disproportionately impacted by climate change, such as individuals with asthma and COPD, and Black and Latinx communities. The results of this study will provide valuable data to understand relationships of temperature and precipitation with asthma and COPD. This data will support future investigation of interventions, such as air purification and community cooling centers, to build resiliency and adaptation to a rapidly warming world.

PI_NAMEs: NASSIKAS, NICHOLAS  (contact)

PROGRAM_OFFICER_NAME: QUINN, ASHLINN KO

PROJECT_TERMS: Address;Adolescent;Adult;Affect;Air;Air Conditioning;air sampling;airborne allergen;airway inflammation;Area;Asthma;Award;Biometry;Black race;Boston;career;career development;Chronic lung disease;Chronic Obstructive Pulmonary Disease;Climate;climate change;climate impact;climate variability;climate-related exposures;Clinical Investigator;cohort;Communities;cooling centers;Critical Care;Data;Development;Development Plans;Devices;Disparity;Dryness;Elderly;Environment;Environmental Epidemiology;Environmental Wind;eosinophil;Epidemiology;epidemiology study;Event;Exposure to;extreme heat;extreme weather;Funding;Future;Global Warming;Goals;Gold;Grant;Health;Health Policy;Heat Stress;Heat Waves;Hospitals;Human;Humidity;IgE;Individual;Institution;Intervention;Investigation;Israel;Knowledge;Latinx;Lead;Lung;Lung Diseases;Manuscripts;Master of Public Health;Measurement;Measures;Mediating;Mediation;Medical;Medical center;member;Mentors;Mentorship;Modeling;Molds;Monitor;mortality;multidisciplinary;National Institute of Environmental Health Sciences;Obstructive Lung Diseases;older adult;Participant;Patient Care;Patients;Peer Review;Persons;Physicians;Physiological;Pollen;Population;Positioning Attribute;Precipitation;prevent;Preventive;promote resilience;Prospective cohort;Prospective Studies;Public Health;Public Health Schools;Public Policy;Publishing;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Questionnaires;Rain;Recording of previous events;recruit;Reporting;Research;Research Activity;Research Design;Research Personnel;respiratory;respiratory health;Respiratory Signs and Symptoms;Rice;Risk;Secondary to;Site;skill acquisition;skills;Smoking;solar radiation;Speed;Spirometry;success;Supervision;Symptoms;Temperature;Testing;Training;United States;Vulnerable Populations;Weather;Woman;Work

PROJECT_TITLE: Climate Variability and Respiratory Health in Asthma and COPD

STUDY_SECTION_NAME: Special Emphasis Panel[ZES1 BWD-D (KS)]


NIH_SPENDING_CATS: Biomedical Imaging;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Elevated phospholipid biosynthesis is a metabolic hallmark of cancer. Our proposal aims to determine whether deuterium metabolic imaging of phospholipid biosynthesis enables longitudinal assessment of brain tumor growth in vivo. Clinical translation of our studies will provide physicians with a much-needed tool to monitor response to therapy in a timely manner in brain tumor patients.

PI_NAMEs: VISWANATH, PAVITHRA  (contact)

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Address;Adult;Anabolism;Anatomy;Biochemical;Biological;Biological Assay;Biological Markers;Biological Process;Blood - brain barrier anatomy;Brain;Brain Neoplasms;brain tissue;Cell Death;Cellular Membrane;Chemical Shift Imaging;chemotherapy;Choline;Choline Kinase;Clinical;Clinical Research;clinical translation;Clinical Trials;Color;Combined Modality Therapy;Contralateral;contrast enhanced;Cytostatics;Data;Decision Making;Deuterium;Development;dietary;Disease Progression;DNA Damage;Doxycycline;drug development;effective therapy;Enzymes;Excision;Glioblastoma;Goals;Growth;Health Care Costs;Histologic;Image;imaging agent;imaging modality;improved;improved outcome;in vivo;innovation;Label;Lecithin;Lesion;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Malignant - descriptor;Malignant Neoplasms;Maps;Measurement;Membrane;Metabolic;metabolic imaging;Metabolism;Modeling;Monitor;Mus;neuro-oncology;non-invasive monitor;Normal tissue morphology;novel;novel therapeutics;Nutrient;Oncology;Operative Surgical Procedures;Outcome;Pathway interactions;Patients;Phosphatidylcholine Biosynthesis;Phospholipids;Phosphorylation;Phosphorylcholine;Physicians;Primary Brain Neoplasms;procedure cost;Production;Prognosis;programs;Proliferating;Property;Quality of life;Radiation;Radiation therapy;Reporting;research and development;response;standard of care;targeted agent;temozolomide;Time;tissue biomarkers;tool;Tracer;treatment response;tumor;Tumor Biology;tumor growth;Tumor Markers;tumor progression;Tumor Tissue;Tumor Volume;Visualization;Xenograft procedure

PROJECT_TITLE: Spatial Mapping of Phospholipid Biosynthesis in Brain Tumors


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Disease

ORG_CITY: DOYLESTOWN

ORG_NAME: BARUCH S. BLUMBERG INSTITUTE

PHR: Project Narrative Antiviral therapeutics approved by the FDA or currently in clinical trials for treatment of chronic hepatitis B can efficiently suppress the replication of hepatitis B virus (HBV), reduce viral load and improve liver pathology, but fail to cure the chronic infection of HBV. This is because those drugs cannot eliminate the most stable HBV replication intermediate, covalently closed circular DNA (cccDNA), in the nuclei of hepatocytes, and viral replication rebounds after discontinuation of treatment. This project addresses the pressing need for the cure of chronic hepatitis B by elimination and/or permanent inactivation of cccDNA with our proprietary chemically ligated guide RNA (lgRNA)-based CRISPR/Cas9 gene editing technology.

PI_NAMEs: GUO, JU-TAO  (contact)

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Achievement;Address;Anti-viral Agents;Binding;Biological Assay;Candidate Disease Gene;Cell Nucleus;Cessation of life;chemical synthesis;Chemicals;Chemistry;Chromatin;Chronic;Chronic Hepatitis B;chronic infection;Circular DNA;clinical development;Clinical Treatment;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;cost effective;delivery vehicle;Dependovirus;Detection;DNA;DNA biosynthesis;DNA Integration;DNA Polymerase Inhibitor;DNA Sequence;Dose;drug discovery;Drug Targeting;efficacy evaluation;Evaluation;FDA approved;Formulation;gene editing technology;Gene Expression;Genes;Goals;Guide RNA;Hepatitis B Virus;Hepatocyte;hepatoma cell;Human;Immune;immunogenicity;improved;In Vitro;in vivo;Laboratories;Length;Ligation;lipid nanoparticle;Liver;manufacture;Messenger RNA;Metabolic;Methods;Modification;Molecular;mouse model;new technology;Pathology;Pegylated Interferon Alfa;Persons;Pharmaceutical Preparations;Phase;Positioning Attribute;pre-clinical;preclinical development;Regimen;Residual state;Ribonucleoproteins;RNA;Role;Specific qualifier value;standard of care;Structure;Supporting Cell;targeted delivery;Technology;Therapeutic;therapeutic candidate;therapeutic evaluation;therapeutic genome editing;therapy development;timeline;Transcriptional Regulation;Treatment Efficacy;Viral;viral DNA;Viral Genes;Viral Genome;Viral Load result;Viral Proteins;Virus Diseases;Virus Replication;Work

PROJECT_TITLE: Chemically ligated-guide RNA (lgRNA)-based CRISPR/Cas9 gene editing for elimination of hepatitis B virus cccDNA


NIH_SPENDING_CATS: Cancer;Clinical Research;Digestive Diseases;Liver Cancer;Liver Disease;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE We propose to test the hypothesis that personalized in vivo models can help identify and characterize therapy- resistant subclones to improve early diagnosis and inform the design and personalized optimization of effective therapies for children with high-risk liver cancers. If proven effective, our proposal will accelerate translational research and facilitate its effective bench-to-bedside implementation to improve the outcomes of children with high-risk liver cancers.

PI_NAMEs: SUMAZIN, PAVEL  (contact)

PROGRAM_OFFICER_NAME: DEY, SUMANA MUKHERJEE

PROJECT_TERMS: Acceleration;Aftercare;Alternative Therapies;Atlases;Base Composition;bench to bedside;Biological Markers;Biological Specimen Banks;Cancer Biology;cancer cell;Cancer Detection;cancer initiation;Cancer Patient;candidate identification;Cell Line;cell type;Cells;Chemoresistance;chemotherapy;Chemotherapy-Oncologic Procedure;Child;Childhood Liver Cancer;Clinical;Clinical Trials;cohort;Combination Drug Therapy;combinatorial;Combined Modality Therapy;Data;design;Development;Diagnosis;Diagnostic;diagnostic signature;Early Diagnosis;effective therapy;Enrollment;Excision;Genetic Transcription;Hepatoblastoma;high risk;High-Risk Cancer;Histone Deacetylase;improved;improved outcome;in vivo Model;inhibitor;innovation;liver cancer patient;Malignant neoplasm of liver;Malignant Neoplasms;Maps;Methods;Modeling;Molecular;Molecular Target;Operative Surgical Procedures;Pathway interactions;patient derived xenograft model;patient response;Patient-Focused Outcomes;Patients;personalized medicine;Population;pre-clinical;Pre-Clinical Model;Prediction of Response to Therapy;predictive marker;predictive modeling;Primary carcinoma of the liver cells;profiles in patients;programs;prospective;Refractory;refractory cancer;Regimen;Relapse;Research;Residual Cancers;Resolution;response;risk prediction;RNA;Sampling;Signal Pathway;Specimen;standard of care;Survival Rate;targeted treatment;Technology;Testing;therapeutic target;therapeutically effective;therapy resistant;tool;trait;Translational Research;treatment response;treatment strategy;tumor;Tumor Burden;tumor diagnosis;Work

PROJECT_TITLE: Discovery of chemoresistant tumor subclones in pediatric liver cancers

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-F (O1)]


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Mental Illness;Neurosciences;Pediatric;Psychosis;Serious Mental Illness

ORG_CITY: LOS ANGELES

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative Neural-immune pathways play a critical role in neurodevelopmental processes and growing evidence suggests that neural-immune gene expression is dysregulated in schizophrenia and other neurodevelopmental, psychiatric disorders. This project will (a) integrate gene expression and genotype data to generate a genome- wide resource for individual-level prediction of neural-immune gene expression, and (b) characterize the impact of genetically predicted neural-immune gene expression on longitudinal trajectories of structural brain development and change in dimensional measures of mental health relevant to psychosis in children and adolescents. Results will significantly expand our understanding of the genetic mechanisms regulating gene expression in the human brain and the developmental etiology of mental illness, thereby informing the development of targeted biologically-based treatments to reduce the burden of disease.

PI_NAMEs: SHARMA, LEANNA MARIE HERNANDEZ (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: 16 year old;Adolescence;Adolescent;Adolescent Development;Affect;age related;age related changes;Architecture;Area;Astrocytes;Attenuated;autism spectrum disorder;autism symptoms;Autopsy;Behavior;Behavioral;Biological Markers;biomarker identification;Bipolar Disorder;Brain;brain based;Brain region;brain tissue;burden of illness;California;career development;cell type;Child;Childhood;Clinical;clinical diagnosis;clinically relevant;Cognition;cognitive change;cognitive development;cognitive process;cohort;Complement;Complex;Data;density;Development;Diagnosis;Dimensions;Disease;disorder risk;Etiology;Event;Fiber;Foundations;Functional disorder;functional genomics;Future;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic architecture;genetic variant;Genetic Variation;genome wide association study;genome-wide;genomic data;Genotype;Goals;Heritability;Heterogeneity;Human;Immune;immune function;Immune signaling;Impulsivity;in vivo;Individual;Individual Differences;inter-individual variation;Interferons;life span;Link;Los Angeles;Measures;medial temporal lobe;Mental disorders;Mental Health;Mentors;Mentorship;Methods;Microglia;Modeling;multi-ethnic;multimodality;National Institute of Mental Health;Nature;neural;Neurites;Neurobiology;neurodevelopment;Neurodevelopmental Disorder;neurogenetics;neuroimaging;NF-kappa B;Pathway interactions;Pattern;Phenotype;phenotypic data;Play;pleiotropism;Population;predictive marker;Probability;Process;prospective;psychiatric symptom;Psychoses;psychosis risk;psychotic;rate of change;Research;Research Domain Criteria;Research Training;Resources;Risk;Role;Sampling;Schizophrenia;sex;Sex Differences;Signal Transduction;SNP genotyping;Social Behavior;Statistical Data Interpretation;Statistical Methods;Strategic Planning;Structure;Surface;symptomatology;Symptoms;synaptic pruning;System;Testing;Thick;Thinness;Training;transcriptome sequencing;transcriptomics;Universities;white matter;Work;Youth

PROJECT_TITLE: Dissecting neural-immune mechanisms of psychosis and related neurodevelopmental disorders

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Liver Cancer;Liver Disease;Rare Diseases

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: Project Narrative: Current treatment options for liver cancer, the third leading cause of cancer-related death, provide only limited survival benefits, in part due to challenges in targeting genetically distinct liver tumors. With this proposal, as a potential therapeutic strategy, we will identify and target the metabolic changes imposed by oncogenic alterations on cancer cell mitochondria, the central biosynthetic hub for cellular metabolism. Combining genetic in vivo liver tumorigenesis models, mitochondrial metabolomics and CRISPR-based functional screens, this proposal will assess oncogene-dependent metabolic limitations of tumor growth in vivo and, provide unprecedented opportunities to exploit metabolic intervention strategies targeting liver cancer.

PI_NAMEs: UNLU, GOKHAN  (contact)

PROGRAM_OFFICER_NAME: BOULANGER-ESPEUT, CORINNE A

PROJECT_TERMS: Address;Anabolism;c-myc Genes;cancer cell;Cancer Etiology;cancer therapy;Cell Line;Cells;Cessation of life;Clinic;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Colorectal Cancer;Complement;Complex;Coupled;Creatine;CRISPR-mediated transcriptional activation;Data;dietary;disease prognosis;driver mutation;Enzymes;Excision;Foundations;gain of function;Genes;Genetic;Genetic Determinism;Genetic Screening;Genotype;Goals;Growth;guanidinoacetate;Hepatocarcinogenesis;Immunoprecipitation;in vivo;insight;interest;Intervention;kinase inhibitor;KRAS oncogenesis;KRASG12D;liquid chromatography mass spectrometry;liver cancer patient;Liver neoplasms;Malignant neoplasm of liver;Malignant neoplasm of pancreas;Maps;Metabolic;Metabolism;metabolomics;Methodology;Methods;Minerals;Mitochondria;mitochondrial metabolism;Modeling;mouse model;mutant;Mutation;Nutrient;Nutritional;Oncogenes;Oncogenic;Operative Surgical Procedures;Organelles;Outcome;patient derived xenograft model;pharmacologic;Phosphocreatine;programs;Proteins;Proteome;Proteomics;Reaction;Resolution;response;Role;screening;success;Supplementation;targeted cancer therapy;targeted treatment;Technology;Testing;Therapeutic;Tissues;TP53 gene;treatment response;tumor;tumor growth;tumor metabolism;tumor progression;Tumor Suppressor Proteins;Tumor Tissue;tumorigenesis;Up-Regulation;uptake;Work

PROJECT_TITLE: Deciphering the role of mitochondrial metabolism in liver cancer

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


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Prostate Cancer;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Urologic Diseases

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE Prostate cancer relies on androgen for growth and is therefore sensitive to androgen-deprivation therapy and antiandrogens. However, the disease can develop therapeutic resistance by transforming from a prostate lineage to a stem cell-like state. This project seeks to characterize the molecular drivers of lineage transformation and resistance to antiandrogens, with the goal to develop an effective therapeutic strategy to target these drivers and suppress the growth of stem cell-like prostate cancer.

PI_NAMEs: WONG, CHEN KHUAN  (contact)

PROJECT_TERMS: Academia;Advisory Committees;Androgen Antagonists;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;Androgens;anti-cancer research;Automobile Driving;Binding;Biological;Biology;Boston;Candidate Disease Gene;career;career development;career networking;Categories;cell growth;Cell Lineage;Cell Maintenance;Cell Nucleus;Cell Survival;Cells;Chromatin;Clinic;combinatorial;Communication;Dependence;Development;Development Plans;Disease;disease model;disorder subtype;Doctor of Philosophy;efficacy evaluation;Ensure;enzalutamide;Epigenetic Process;epigenomics;Evaluation;Exposure to;FOSL1 gene;Foundations;functional genomics;Future;Genetic;Genetic Transcription;Genomic approach;Goals;Growth;Human;Impairment;improved;In Vitro;in vivo;inhibitor;insight;interest;Knowledge;Laboratories;Leadership;Ligand Binding Domain;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;medical schools;Medicine;Memorial Sloan-Kettering Cancer Center;Mentors;Modeling;Molecular;Mutation;Neuroendocrine Prostate Cancer;Neurosecretory Systems;next generation;Oncogenic;Oncology;Organoids;overexpression;Pathogenesis;Pathway interactions;Patients;Phenotype;Postdoctoral Fellow;Pre-Clinical Model;pressure;prevent;programs;Prostate;prostate cancer cell;Prostatic Neoplasms;receptor;Receptor Signaling;Research;research and development;Research Personnel;Resistance;resistance mechanism;Role;Signal Transduction;skills;small molecule inhibitor;stem cell growth;stemness;success;Supervision;targeted treatment;Technical Expertise;Therapeutic;therapeutic evaluation;therapeutic target;therapeutically effective;therapy resistant;Training;transcription factor;transcriptomics;transdifferentiation;tumor growth;tumor progression;Universities

PROJECT_TITLE: Dissecting FOSL1-mediated lineage plasticity and resistance to androgen receptor signaling inhibition in prostate cancer