NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Immunotherapy;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_DEPT: NEUROSURGERY

PHR: PROJECT NARRATIVE After traumatic brain injury, the peripheral immune system and the injured brain interact with one another to exacerbate neuropathology and induce immunosuppression which can lead to chronic neurological deficits and increased susceptibility to secondary infections and death. However, the extent, mechanism(s), and duration of the effects of the peripheral immune system and the injured brain on each other is largely unknown. Within this proposal, we aim to investigate the interactions between these two organ systems in a clinically relevant injury model in order to understand neuro-immune interactions and to develop a translational treatment strategy that employs the immune system to protect the damaged brain.

PI_NAMEs: WOFFORD, KATHRYN LEIGH (contact)

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: 3-Dimensional;Acceleration;Affect;animal facility;Animal Model;Animals;Anti-Inflammatory Agents;Autologous;Axon;Basic Science;Behavior;Behavioral;Biological Assay;Biomechanics;Blood;Blood - brain barrier anatomy;Body System;Brain;Brain Injuries;career;career development;Caring;Cell Separation;Cells;Cessation of life;Chronic;Clinical Pathology;clinically relevant;cytokine;Cytoskeleton;Death Rate;design;Devices;Diffuse;Environment;Equipment;Exhibits;fabrication;Family suidae;Female;Flow Cytometry;Fostering;Gene Expression;Head;Health;Home;Homeostasis;Homing;Immune;immune activation;immune cell infiltrate;Immune response;Immune system;immunodeficiency;immunoengineering;Immunohistochemistry;Immunology;immunomodulatory strategy;immunoregulation;Immunosuppression;Impairment;improved;In Vitro;in vitro Assay;in vivo;Individual;Infection;Infiltration;Inflammatory;Injury;innovation;Institution;intravenous administration;K-Series Research Career Programs;Laboratories;Laboratory Research;Limes;Location;lymphoid organ;Macrophage;male;Medical center;Mentors;Mentorship;minimally invasive;Modeling;monocyte;Myelin;National Institute of Neurological Disorders and Stroke;Nerve Regeneration;Nervous System;Nervous System Trauma;Neuroimmune;neuroimmunology;neuroinflammation;Neurologic Deficit;Neurological outcome;neuronal circuitry;neuronal survival;Neurons;neuropathology;neurophysiology;neuroprotection;new technology;novel;Organ Size;Outcome;particle;Pathologic;Pennsylvania;Peripheral;peripheral blood;Persons;Phagocytosis;Phenotype;porcine model;pre-clinical;Predisposition;Production;Protein Secretion;Reactive Oxygen Species;Regenerative capacity;regenerative tissue;Research;Research Personnel;Resources;secondary infection;Secondary to;Signal Transduction;Site;Testing;Therapeutic;Time;tissue processing;tissue regeneration;Tissues;tool;Training;training opportunity;translational approach;Trauma;Traumatic Brain Injury;Treatment Efficacy;treatment strategy;Universities;Vascular blood supply;Whole Blood;Work

PROJECT_TITLE: Understanding and Controlling Neuro-immune Interactions Following Traumatic Brain Injury


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Neurosciences

ORG_CITY: DAVIS

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: Project Narrative Transforming rich and continuous experience into concise and temporally associated event sequences (i.e., event segmentation), a fundamental process for episodic memory, relies on the coordination between the hippocampus, prefrontal cortex, and substantia nigra. This proposal aims to reveal the underlying circuit-level neural dynamics using direct neural recordings (at both the single-cell and population levels), computational modeling, and electrical stimulation. The expected outcomes of this study will provide valuable insights on event segmentation and its influence on episodic memory in humans, which will shed light on developing neural prosthetics to help patients with memory-related disorders.

PI_NAMEs: ZHENG, JIE  (contact)

PROGRAM_OFFICER_NAME: JOHNSON, KARI ANNE

PROJECT_TERMS: Address;Advanced Development;Area;Behavior;behavior measurement;Behavioral;Brain;Cells;Clinical;Clip;Cognitive;computational neuroscience;Computer Models;Data;deep brain stimulator;Detection;deviant;Disease;dopaminergic neuron;Electric Stimulation;Electrodes;Episodic memory;Euclidean Space;Event;experience;Failure;Feedback;Goals;high dimensionality;Hippocampus;Hour;Human;Image;Impairment;implantation;Implanted Electrodes;Influentials;insight;Lead;Learning;Lesion;Link;member;Memory;Memory Disorders;Memory impairment;memory recognition;Mentors;Microscopic;Midbrain structure;Modeling;Monitor;movie;multisensory;neural;neural prosthesis;neuromechanism;Neurons;Neurosciences;novel;Outcome;Outcome Study;Patients;Phase;Population;Prefrontal Cortex;Process;Property;Proxy;Research;response;Retrieval;Rewards;Role;Seizures;sensory input;Series;Shapes;Signal Transduction;Structure;Substantia nigra structure;System;Technical Expertise;Testing;Theoretical model;Therapeutic Intervention;Time;Training;Update;Work

PROJECT_TITLE: Circuit Dynamics of Structuring Episodic Memories in Humans


ADMINISTERING_IC: CA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: LA JOLLA

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative Perineural invasion (PNI) is found in nearly all patients with pancreatic ductal adenocarcinomas (PDAC) and is associated with an increased incidence of tumor metastasis. PNI is a dynamic process in which distinct cellular players of the tumor microenvironment help tumor cells invade autonomic nerve fibers. The proposed work would help to explain how tumor cells, nerves and immune cells communicate in the setting of PNI.

PI_NAMEs: WEITZ, JONATHAN ROBERT (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Acetylcholine;Adoptive Transfer;Adrenergic Agents;adrenergic block;Adrenergic Receptor;Antitumor Response;autonomic nerve;Autonomic nervous system;Binding;Biology;Bone Marrow;Cancer Model;Cell Communication;Cell Physiology;Cell Proliferation;Cell surface;Cells;cellular targeting;chemical release;chemokine;clinical investigation;Communication;Complex;cytokine;Data;Death Rate;Disabling;Disease;Doctor of Philosophy;Enzymes;Failure;Genes;glial cell-line derived neurotrophic factor;Histologic;Human;human tissue;Immune;immune function;Immune system;immunogenicity;Immunosuppression;Immunotherapeutic agent;Immunotherapy;improved;In Situ;in vivo;Incidence;Intervention Studies;Invaded;Investigation;Knock-out;KPC model;Label;Macrophage;Malignant Neoplasms;Mediating;Methaqualone;Modeling;Molecular;Molecular Target;mouse model;Mus;nano-string;Neoplasm Metastasis;neoplastic cell;Nerve;Nerve Fibers;neural;Neuroimmune;Neurons;neurotransmitter release;Neurotransmitters;Norepinephrine;novel therapeutic intervention;Pancreas;Pancreatic Adenocarcinoma;pancreatic cancer model;Pancreatic Ductal Adenocarcinoma;pancreatic neoplasm;Paracrine Communication;Patient-Focused Outcomes;Patients;perineural;Physiological;Play;Population;Process;Production;Prognostic Factor;reconstruction;response;Role;Signal Transduction;Site;Slice;technology platform;Tissues;tool;transcriptomics;tumor;Tumor Cell Invasion;tumor microenvironment;tumor progression;Tumor Promotion;tumor-immune system interactions;Tumor-infiltrating immune cells;tumorigenic;Visualization;Work

PROJECT_TITLE: The role of sympathetic nerve associated macrophages during pancreatic adenocarcinoma progression


ADMINISTERING_IC: AG

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

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);Biotechnology;Brain Disorders;Dementia;Genetics;Lead Poisoning;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative This proposal aims to identify novel gene-environmental (GxE) interactions that contribute to Pb-induced risk of Alzheimer's disease and related dementia (AD/ADRD) in aging brains by establishing a screening platform based on CRISPR a/i and elucidate the interactions between Pb-exposure and aging using engineered human neuronal models. Novel GxE targets will be identified and compared with those found using conventional approach. The collective findings will establish a new research paradigm for studying GxE interactions contributing to ADRD.

PI_NAMEs: XU, RANJIE ;YUAN, CHONGLI  (contact)

PROGRAM_OFFICER_NAME: YAO, ALISON Q

PROJECT_TERMS: 3-Dimensional;Acceleration;Address;Affect;Age;age acceleration;age effect;age related;Aging;aging brain;aging process;aging related;Alzheimer's disease related dementia;Alzheimer's disease risk;Area;Automobile Driving;biological age;Biological Models;Brain;Cell Aging;Cell Nucleus;Central Nervous System;Chemicals;Chimera organism;Clustered Regularly Interspaced Short Palindromic Repeats;Confounding Factors (Epidemiology);Coupled;Coupling;CRISPR-mediated transcriptional activation;design;Development;Diagnosis;Disease;DNA Methylation;empowerment;Engineering;Environment;Environmental Risk Factor;environmental stressor;Epigenetic Process;Etiology;Experimental Models;Exposure to;extracellular;familial Alzheimer disease;Formulation;Foundations;Future;Genes;Genetic;genetic risk factor;genetic selection;Goals;hallmarks of aging;Health;Health Care Costs;Healthcare;healthcare burden;Heredity;Heterochromatin;high throughput screening;Human;Human Engineering;human induced pluripotent stem cells;In Vitro;Induced pluripotent stem cell derived human neuron;Knowledge;Lead;lead exposure;Lead Poisoning;Life;Mitochondria;Modeling;Monitor;Mus;Neurologic;Neurological outcome;Neurons;neurotoxicity;novel;Nuclear;Other Genetics;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Plasmids;Population;Reporter;Research;Risk;Risk Factors;Scheme;screening;Shapes;Signal Pathway;Signal Transduction;Societies;Sorting;tau aggregation;Work

PROJECT_TITLE: Elucidate Gene-environmental interactions employed by Pb in promoting ADRD in aging brains

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-P (M1)]


ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: NARRATIVE This project will investigate the use of proton pencil beam scanning (PBS) to deliver FLASH enhanced radiotherapy. The approach will examine the complex interplay between spatio-temporal beam parameters and FLASH, optimization algorithms for modeling biological effects and treatment planning, and development of FLASH specific methods for ultra-fast dose monitoring, robotic positioning, image guidance, and quality assurance. The goal is to further optimize the FLASH effect by PBS machine tuning and FLASH delivery with existing clinical proton accelerator technology.

PI_NAMEs: KOUMENIS, CONSTANTINOS  (contact);LIN, ALEXANDER

PROGRAM_OFFICER_NAME: BUCHSBAUM, JEFFREY

PROJECT_TERMS: 3-Dimensional;Affect;Algorithms;Animals;Area;arm;artificial intelligence method;Binding;Biological;Biological Assay;Biological Models;Blood Vessels;career;Cell Proliferation;Cells;Clinical;clinical translation;Collimator;Complex;Computer software;cost;Data;Development;Differential Equation;Diffusion;Dimensions;DNA Damage;DNA Double Strand Break;doctoral student;Dose;Dose Rate;EF5;Equipment;experience;Funding;Future;Gamma-H2AX;Genetic Recombination;Geometry;Goals;Image;image guided;In Vitro;in vivo;instrumentation;Investigation;ionization;Ions;irradiation;Lead;Location;Magnetism;Malignant Neoplasms;Measures;Medical;Methods;Modality;Modeling;models and simulation;Modernization;Monitor;mouse model;Movement;Mus;nanoparticle;Normal tissue morphology;Outcome;Oxygen;particle;Patients;Pennsylvania;Phase I Clinical Trials;phosphorescence;Physics;Platinum;Positioning Attribute;pre-clinical;Procedures;Process;programs;proton beam;Proton Radiation;proton therapy;Protons;quality assurance;Quality of life;Radiation;Radiation therapy;radiochemical;Reporting;Research;Research Personnel;Robotics;Role;Scanning;Signal Transduction;simulation;Skin;spatial temporal variation;spatiotemporal;Speed;Spottings;Stains;Structure;Students;success;Supervision;Surface;System;Tail;Targeted Radiotherapy;Techniques;Technology;Time;Tissues;tool;Toxic effect;translational study;Translations;Treatment outcome;treatment planning;tumor;tumor growth;undergraduate student;United States National Institutes of Health;Universities;Validation;Variant;Work

PROJECT_TITLE: Translational Studies in FLASH Particle Radiotherapy


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biomedical Imaging;Biotechnology;Brain Disorders;Climate-Related Exposures and Conditions;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CHAPEL HILL

ORG_DEPT: GENETICS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative Common genetic variants identified through genome-wide association studies have been reproducibly associated with risk for Alzheimer’s disease (AD), but the function of many risk variants are unknown and likely context-specific. At the same time, several environmental exposures have been implicated in AD and dementia, including particulate matter air pollution (PM2.5), heavy metals (especially lead (Pb)), and infections. Here, will identify interactions between genetic variants and the aforementioned exposures that influence neural cells, brain structure, and AD.

PI_NAMEs: STEIN, JASON LOUIS (contact)

PROJECT_TERMS: Affect;Air Pollution;Alzheimer's Disease;Alzheimer's disease risk;Area;Autopsy;biobank;Brain;brain cell;brain tissue;Categories;Cell Culture Techniques;Cell Differentiation process;Cell Survival;cell type;Cells;Censuses;Complement;Data;Databases;Dementia;Development;Diffusion Magnetic Resonance Imaging;donor stem cell;Environmental Exposure;Exposure to;fine particles;Functional Magnetic Resonance Imaging;gene environment interaction;Gene Expression;Gene Expression Regulation;Genes;genetic architecture;genetic association;genetic variant;Genetic Variation;genome wide association study;Genotype;Goals;Heavy Metals;Human;In Vitro;in vitro Model;in vivo;induced pluripotent stem cell;Infection;Interferon Type II;Lead;Magnetic Resonance Imaging;Modeling;Molecular;Nature;nerve stem cell;Neurons;Organoids;Outcome;Particulate Matter;Pathway interactions;Phenotype;polygenic risk score;Population;Quantitative Trait Loci;Regulation;Reproducibility;response;risk variant;single-cell RNA sequencing;Structure;Surface;System;Techniques;Testing;Thick;Time;Tissues;Translating;Untranslated RNA;Variant;white matter

PROJECT_TITLE: AD GxE: In vivo and in vitro modeling of gene x environment interactions


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Asthma;Behavioral and Social Science;Building Research Capacity at Institutions with Limited NIH Funding;Clinical Research;Lung;Pediatric

ORG_CITY: DENTON

ORG_NAME: TEXAS WOMAN'S UNIVERSITY

ORG_STATE: TX

PHR: Project Narrative This proposed study has public health relevance due to the high prevalence of asthma in adolescence and their reactive management style that can lead to symptom exacerbations and increased healthcare cost. Although self-management is a critical element in achieving asthma control, a recent systematic review revealed that existing measures for assessing adolescent asthma self-management are limited in scope and lack validation, failing to account for cognitive processes and self-regulation characteristics. The proposed study aims to address the high prevalence of asthma in adolescence and bridge the gap by creating and validating an asthma self-management questionnaire for adolescents aged 12 to 21.

PI_NAMEs: ISIK, ELIF  (contact)

PROGRAM_OFFICER_NAME: FREEMER, MICHELLE M

PROJECT_TERMS: 21 year old;Academic Research Enhancement Awards;Address;Adolescence;Adolescent;Adolescent Development;Adult;Age;aged;Asthma;Behavior;Caring;Characteristics;Charge;Child;Clinic;Clinical;clinical practice;Cognitive;cognitive interview;cognitive process;design;Development;Economic Burden;Education;Educational Intervention;Elements;Ensure;experience;Face;Factor Analysis;Faculty;Feedback;Frequencies;Goals;Grant;Guidelines;Health;Health behavior;Health Care Costs;High Prevalence;improved;Informal Social Control;innovation;insight;interest;Learning;Literature;Measures;Methods;Modeling;Monitor;Morbidity - disease rate;mortality;multidisciplinary;novel;Patient Self-Report;Patients;Phase;Phase Transition;Play;Prevention program;Property;Psychometrics;Public Health;public health relevance;Publishing;Quality of life;Questionnaires;recruit;Research;Research Personnel;Respondent;Role;Sampling;Schools;Self Efficacy;Self Management;skills;Students;Symptoms;systematic review;Techniques;Testing;tool;transition to adulthood;United States National Institutes of Health;Validation;vulnerable adolescent;Work;Writing

PROJECT_TITLE: Asthma Self-Management Behaviors and Cognitive Autonomy: Developing an Adolescent Questionnaire

STUDY_SECTION: BMHO

STUDY_SECTION_NAME: Biobehavioral Medicine and Health Outcomes Study Section[BMHO]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding

ORG_CITY: WILMINGTON

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF NORTH CAROLINA WILMINGTON

PHR: Project Narrative The proposed research is relevant to public health because the investigation of new chemical reactions leads to improvement in pharmaceuticals available to treat human diseases. Specifically, chiral nitrogen-containing organic synthons will be generated in an economical fashion. The project is in line with part of the NIH’s mission because an increase in fundamental knowledge will enable the development of previously unavailable medications for the enhancement of human health. 1

PI_NAMEs: MORGAN, JEREMY B (contact)

PROGRAM_OFFICER_NAME: FABIAN, MILES

PROJECT_TERMS: Acids;Alkylation;Amines;Aziridines;Carbon;Catalysis;catalyst;chemical reaction;Chemicals;Complex;Data;Development;Disease;drug development;Electrons;enantiomer;enolate;Epoxy Compounds;Esters;Goals;Health;Human;human disease;improved;Individual;Indoles;indoline;innovation;Investigation;Kinetics;Knowledge;Marketing;Methods;Mission;molecular asymmetry;National Institute of Mental Health;Nitrogen;novel;Organic Synthesis;Organism;Outcome;Palladium;Pathway interactions;Pharmaceutical Preparations;Pharmacologic Substance;Process;Psychotropic Drugs;Public Health;Reaction;Research;research and development;Resolution;Scheme;screening program;small molecule;Testing;undergraduate research experience;undergraduate student;United States National Institutes of Health

PROJECT_TITLE: Enantioenriched Nitrogen-Containing Small Molecules via Stereoselective Carbon-Carbon Bond Construction

STUDY_SECTION: CSB

STUDY_SECTION_NAME: Chemical Synthesis and Biosynthesis Study Section[CSB]


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;Infectious Diseases;Neurodegenerative;Neurosciences;Sexually Transmitted Infections;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: WORCESTER

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: PROJECT NARRATIVE Cadmium (Cd) heavy metal exposure has been implicated in its role to increase risk for Alzheimer’s Disease (AD) and our proposal aims to study the role of genetic variation within immune genes to determine the extent of such genetic variation interacting with Cd exposure to cause AD. We plan to do so by the using a selected population of donor cells containing such variation, reprogramming them into induced pluripotent stem cells (iPSCs) for differentiating into cerebral organoids (cOrgs) and testing for AD pathology by exposing the cOrgs to Cd and infecting them with herpes simplex 1 virus (HSV-1). We propose 3 complementary aims that utilize RNA-sequencing data, flow cytometery detection of AD and cell-type biomarkers as well as measuring the levels of multiple pro-inflammatory cytokines of the various cOrgs upon Cd exposure as well as HSV-1 infection.

PI_NAMEs: CHAN, YING LEONG  (contact)

PROJECT_TERMS: 3-Dimensional;abeta deposition;Acceleration;Affect;Alleles;Alzheimer disease detection;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Alzheimer's disease risk;Alzheimer's disease test;Alzheimer’s disease biomarker;Amyloid beta-Protein;Astrocytes;Autopsy;Biological;Biological Markers;brain tissue;Cadmium;CCL2 gene;CCL3 gene;cell type;Cells;Cerebrum;cytokine;Data;Disease Marker;Donor Selection;Enzyme-Linked Immunosorbent Assay;EPHA1 gene;Exposure to;Flow Cytometry;gene network;Genes;Genetic;Genetic Diseases;genetic variant;Genetic Variation;Genome;Glial Fibrillary Acidic Protein;Heavy Metals;Herpes Simplex Infections;Herpesvirus 1;Human;IL17 gene;IL18 gene;IL8 gene;Immune;immune function;Immune system;In Vitro;in vivo Model;Individual;induced pluripotent stem cell;Inflammatory;insight;Interferon Type II;Interleukin-1 alpha;Interleukin-10;Interleukin-2;Interleukin-6;Link;lymphoblastoid cell line;Measurement;Measures;Metal exposure;Microglia;Modeling;molecular marker;mortality;Neurodegenerative Disorders;neuroinflammation;Neurons;novel;Oligodendroglia;Organoids;Pathogenesis;Pathway interactions;Pattern;Phenotype;Population;Process;RANTES;Risk;risk variant;Role;Signal Transduction;SPI1 gene;Stains;stem cell differentiation;tau-1;Testing;TNF gene;Toxic effect;transcriptome sequencing;transcriptomics;TREM2 gene;Urine;Variant;Viral;Virus;Virus Diseases;Work

PROJECT_TITLE: Examining the effect of cadmium metal exposure on Alzheimer's disease genetic alleles using herpes viral infected cerebral organoids


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Nutrition;Obesity;Prevention;Women's Health Research

ORG_CITY: SALT LAKE CITY

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Narrative Persons with obesity have an increased risk of developing breast cancer. Our proposed research will address how obesity increases breast cancer growth and suggest new drugs to treat these patients. Thus, the proposed research is of high relevance to public health and perfectly aligns with NCI mission to support cancer research to advance scientific knowledge and help all people live longer, healthier lives.

PI_NAMEs: CHAIX, AMANDINE H. (contact);DUCKER, GREGORY S;HILGENDORF, KEREN

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: absorption;Acceleration;Address;Adipose tissue;Adjuvant Therapy;Adopted;Affect;Anabolism;Animal Model;anti-cancer research;Apolipoprotein E;Biochemical;Biology;Biomass;Body mass index;Body Weight decreased;Breast Cancer Cell;Breast Cancer cell line;Breast Cancer Treatment;Caloric Restriction;Cancer and Nutrition;cancer cell;Cancer Cell Growth;Chronic;Clinical Trials;combat;Complex;Data;Dependence;Development;Diet;diet-induced obesity;dietary;Dietary Fats;Dietary Intervention;dietary restriction;Environment;experimental study;Fatty acid glycerol esters;Fatty Acids;feeding;Female;Future;Genes;Genetic;Glucose;Goals;Grant;Growth;Health;Human;Hyperinsulinism;in vivo;Incidence;Infusion procedures;inhibitor;Insulin;Insulin Resistance;insulin sensitivity;Intervention;Isotope Labeling;ketogenic diet;Knock-out;Knockout Mice;Knowledge;Link;lipid biosynthesis;lipid metabolism;Lipids;Lipolysis;Lipomatous neoplasm;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Measures;Menopausal Status;Metabolic;Metabolic syndrome;Metabolism;Mission;Modeling;modifiable risk;Morbidity - disease rate;mortality;mouse model;Mus;Neoplasm Metastasis;Nonesterified Fatty Acids;novel therapeutic intervention;novel therapeutics;Nutrient;Nutrient availability;nutrition;obese patients;Obesity;obesity treatment;Patients;Persons;pharmacologic;Physiology;Population;Postmenopause;programs;Public Health;Publishing;Recurrence;Research;Research Proposals;Risk;Risk Factors;Scientific Advances and Accomplishments;Smoking;Source;stable isotope;symposium;System;targeted treatment;Testing;Therapeutic;therapeutic development;therapeutic evaluation;Therapeutic Intervention;therapeutic target;Thinness;transcriptomics;Transgenic Mice;triple-negative invasive breast carcinoma;tumor;tumor growth;tumor metabolism;tumor microenvironment;uptake;Woman

PROJECT_TITLE: Dietary lipids as drivers and therapeutic targets in obesity-accelerated breast cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-F (M2)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cancer;Immunotherapy;Mental Health;Neurosciences

ORG_CITY: BALTIMORE

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Chronic stress is significantly linked to an elevated risk of metastasis and cancer recurrence, yet there remains a substantial knowledge gap regarding the underlying mechanisms driving this process. We discovered that stress induces the formation of metastasis-promoting neutrophil extracellular traps and local activation of the sympathetic nervous system at the metastatic site, while reciprocally metastasis alters the activity of stress-regulating neurons in the brain, thus establishing a stress-metastasis feedforward loop. In this application, we propose to elucidate the mechanisms driving this feedforward loop, with implications for preventing metastasis from disseminated cancer cells and treating stage IV cancer.

PI_NAMEs: EGEBLAD, MIKALA  (contact);VAN AELST, LINDA

PROGRAM_OFFICER_NAME: GRIL, BRUNILDE M

PROJECT_TERMS: Adrenal Glands;Adrenergic Agents;Adrenergic Receptor;Affect;Animal Model;Automobile Driving;Back;biological adaptation to stress;Body System;Brain;cancer cell;Cancer Patient;cancer recurrence;Cell Communication;Cells;Chronic;Chronic stress;Communication;Corticotropin;Corticotropin-Releasing Hormone;Data;Discipline;Disseminated Malignant Neoplasm;Electrophysiology (science);epidemiological model;Esthesia;Evolution;experience;Exposure to;extracellular;Family;FDA approved;Feedback;Fright;Future;genetic manipulation;Glucocorticoids;Goals;Human;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;Immune;immune checkpoint blockade;Immune system;improved;insight;Interruption;Ion Channel;Knowledge;Link;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Metastasis Induction;Metastatic breast cancer;Micrometastasis;mouse model;Mus;Neoplasm Metastasis;Neoplasms;Nerve;nerve supply;Neuroimmune;Neurons;neurophysiology;Neurosciences;Neurosecretory Systems;Neurotransmitters;neutrophil;Norepinephrine;novel;paraventricular nucleus;Patients;Physiological;Pituitary Gland;Population;Positioning Attribute;prevent;Process;Prognosis;Property;Protocols documentation;Psychological Stress;Recurrence;Resistance;response;Risk;Sensory;Signal Transduction;Site;Stimulus;Stress;Stressful Event;Stromal Cells;Study models;Sympathetic Nervous System;System;Techniques;Testing;Therapeutic;therapy outcome;treatment response;tumor immunology;tumor microenvironment

PROJECT_TITLE: Defining brain-body feedback loops mediating stress-induced metastasis

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RTRB-S (M1)]


ADMINISTERING_IC: MH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Mental Health;Mental Illness;Neurosciences;Pediatric;Serious Mental Illness

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE This project supports the purchase of a next-generation 3 Tesla human MRI scanner at the Athinoula A. Martinos Center for Biomedical Imaging to serve a diverse array of NIMH- and NIH-funded studies at Mass General Brigham and across the greater Boston area research community. The new 3 Tesla human MRI will replace the obsolete scanner in the Martinos Center PET-MR & Radiochemistry Facility. It will also boost the imaging performance and provide major benefits to structural, functional, and multimodality PET-MR imaging and microstructural tissue characterization for understanding mental health and psychiatric disorders.

PI_NAMEs: CATANA, CIPRIAN ;HUANG, SUSIE YI (contact)

PROGRAM_OFFICER_NAME: LIU, CHRISTINA HUANG

PROJECT_TERMS: 15 year old;16 year old;Acceleration;Alzheimer's Disease;Architecture;Area;autism spectrum disorder;Award;base;biomedical imaging;Bipolar Disorder;Boston;Brain;Cognitive;Communities;Computer software;Computers;cost;density;frontier;Funding;Grant;Human;Imaging Techniques;innovation;instrument;instrumentation;Investigation;Leadership;Magnetic Resonance Imaging;Maintenance;Major Depressive Disorder;Mental disorders;Mental Health;Modernization;Molecular;National Institute of Mental Health;neuroimaging;neuroregulation;Neurosciences;next generation;Obsessive-Compulsive Disorder;Performance;Physiologic Monitoring;Positron-Emission Tomography;pressure;Price;Productivity;prototype;Radiology Specialty;Research;Research Personnel;Resources;Schizophrenia;Secure;Sensitivity and Specificity;Services;Site;Specificity;Standardization;Structure;Structure-Activity Relationship;System;Technology;technology development;Therapeutic;United States National Institutes of Health;Vendor

PROJECT_TITLE: Next-Generation 3 Tesla Human MRI Scanner for Mental Health Research

STUDY_SECTION_NAME: Special Emphasis Panel[ZMH1 ERB-E (03)]


NIH_SPENDING_CATS: Aging;Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Parkinson's Disease;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Stem Cell Research - Nonembryonic - Human

ORG_CITY: SAN DIEGO

ORG_NAME: SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE

PHR: Narrative Neuroinflammation is believed to contribute to the onset and/or the progression of neurodegenerative diseases. We propose experiments to test the hypothesis that during neuroinflammation, the cytokine IL-13 contributes to the loss of dopaminergic neurons expressing its receptor, IL-13Rα1. The originality and potential clinical significance of this work lie in the hypothesis that an anti-inflammatory cytokine can contribute to neurodegeneration. This represents a paradigm shift from the current view that anti-inflammatory cytokines are invariably neuroprotective and may open the way to novel therapeutic strategies. If successful, these experiments will show that IL-13 and IL-13Rα1 are potential novel targets for preventing Parkinson’s disease or slowing its progression, at least in a subset of patients.

PI_NAMEs: CONTI, BRUNO  (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, LUIS FLANAGAN

PROJECT_TERMS: Abbreviations;Ablation;Affect;alpha synuclein;Alzheimer's Disease;Animals;Anti-Inflammatory Agents;Brain;Cell Death;Cell Line;Cells;Chemosensitization;Chronic;Chronic stress;clinically significant;cytokine;cytotoxic;Deposition;Development;Diagnosis;Disease;Dopaminergic Cell;dopaminergic neuron;early onset;experimental study;Fatty-acid synthase;FDA approved;gain of function;Generations;Genes;Genetic;Genetic Polymorphism;genetic variant;glial activation;Homologous Gene;Human;human embryonic stem cell;Hydrogen Peroxide;IL-13Ralpha1;IL13RA1 gene;In Situ Hybridization;In Vitro;in vivo;Individual;induced pluripotent stem cell;Inflammatory;inhibitor;Interleukin 4 Receptor;Interleukin-13;Interleukin-4;Knockout Mice;Laboratories;Leucine;Linkage Disequilibrium;Lipopolysaccharides;locus ceruleus structure;LoxP-flanked allele;male;Mediating;Microglia;Midbrain structure;mitochondrial dysfunction;Modeling;Molecular;mouse model;Mus;mutant;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neuroimmune;neuroinflammation;neuron loss;Neurons;neuroprotection;neurotoxicity;noradrenergic;novel;novel therapeutic intervention;Odds Ratio;originality;Oxidants;oxidative damage;Oxidative Stress;Parkinson Disease;pars compacta;Pathogenicity;Pathology;Pathway interactions;patient subsets;Patients;Pattern;Peroxides;Pharmaceutical Preparations;phase I trial;Phenotype;Positioning Attribute;Predisposition;prevent;Proline;Publishing;Reactive Oxygen Species;receptor;Reporter;Reporting;Risk;Role;Signal Pathway;Signal Transduction;Single Nucleotide Polymorphism;Substantia nigra structure;synucleinopathy;System;Testing;Toxic effect;trait;transcriptome;Transgenic Mice;Tyrosine 3-Monooxygenase;Variant;Virus;Work;X Chromosome

PROJECT_TITLE: Anti-inflammatory signals and neurodegeneration

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Climate-Related Exposures and Conditions;Dementia;Genetics;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Project Narrative Growing evidence suggests that the potential causes of Alzheimer’s disease (AD) and AD-related dementias (ADRD) in the aging population are multi-faceted and are likely mediated through an interaction of genetic and environmental risk factors (GxE), such as air pollution. In this application, using human induced pluripotent stem cell (hiPSC) and in vivo xenotransplantation models with different AD-related genetic backgrounds, we will study the targets of aberrant protein S-nitrosylation as mediators of the GxE interactions. Our proposed study will gain molecular insight into the air pollution-related cognitive decline in AD/ADRD, thus identifying potential new therapeutic targets.

PI_NAMEs: LIPTON, STUART A (contact);NAKAMURA, TOMOHIRO

PROJECT_TERMS: 3-Dimensional;Age;Age Years;aging population;Air Pollution;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease patient;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer's disease therapy;Anions;Apolipoprotein E;apolipoprotein E-4;Astrocytes;Autopsy;Bioenergetics;Biological Models;biological systems;Black Populations;Brain;Caucasians;Cerebrum;Chronic;Cysteine;Dementia;dementia risk;DNA Sequence Alteration;Dose;Electrophysiology (science);Environmental Exposure;Environmental Risk Factor;Etiology;exhaust;exposed human population;Exposure to;fine particles;Future;gene environment interaction;Genetic;genetic risk factor;genetic variant;Human;human disease;human induced pluripotent stem cells;humanized mouse;Impaired cognition;in vivo;Injury;insight;Knock-in Mouse;Latino Population;Lead;Life Style;Link;Mass Spectrum Analysis;Mediating;Mediator;Metabolic;Microglia;Mitochondria;Molecular;mouse model;Mus;mutant;Mutation;Neurodegenerative Disorders;neuroinflammation;neuron loss;Neurons;neuropathology;neurotransmission;new therapeutic target;Nitric Oxide;Nitrogen;nitrosative stress;novel;Organoids;Oxidation-Reduction;Oxidative Stress;Oxygen;Particulate Matter;Pathogenesis;Patients;Phenotype;Post-Translational Protein Processing;Power Plants;Protein Isoforms;Protein S;Proteins;Publishing;Reaction;response;Risk;S-Nitrosothiols;sex;stem cell model;Sulfhydryl Compounds;Synapses;targeted treatment;Testing;Therapeutic Intervention;therapeutic target;Variant;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Aberrant protein S-nitrosylation mediates Gene-Environment Interactions in AD/ADRD


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

ORG_CITY: TAMPA

ORG_NAME: UNIVERSITY OF SOUTH FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE In one sense, cancer represents an imbalance between pro-inflammatory and pro-resolving processes that promote tumor growth and suppress the immunity of the tumor microenvironment (TME). Here, we plan to understand how AA-rich Western diets are metabolized by ALOX5 and related genes that regulate the TME. These studies will lead to new therapeutic approaches to CRC through modulation of lipid-signaling in the TME.

PI_NAMEs: HALADE, GANESH V;YEATMAN, TIMOTHY J (contact)

PROGRAM_OFFICER_NAME: KAI, MIHOKO

PROJECT_TERMS: Affect;Air;Apoptosis;Apoptotic;Arachidonic Acids;Bioinformatics;Cancer Biology;cancer cell;cancer survival;cancer therapy;Cardiology;Cell membrane;Cellularity;Chronic;Classification;Clinical;cohort;Collaborations;Colorectal Cancer;colorectal cancer progression;Consensus;Data;Data Set;Development;Diet;Dietary Supplementation;Disease;Ensure;Enzymes;Essential Fatty Acids;Genes;Genetic;Genomics;Genotype;Growth;healing;Human;human data;Hydroxyeicosatetraenoic Acids;Immune;immune activation;Immune checkpoint inhibitor;Immunity;Immunosuppression;Implant;improved;In Vitro;in vivo;Inflammation;Inflammatory;Leukotriene B4;Link;lipid mediator;lipid metabolism;lipidomics;Lipids;lipoxin B4;Lipoxygenase;Liquid substance;Macrophage;Malignant Neoplasms;MC38;Mediator;Metabolism;migration;Modeling;Molecular;molecular subtypes;mouse model;multiple omics;Mus;Natural Immunity;neoplastic cell;novel;novel strategies;novel therapeutic intervention;nutrition;Organoids;Outcome;overexpression;Pathologic;Pathway interactions;Patients;Play;Process;Prognosis;prognostic;Proliferating;Publishing;Research;Research Personnel;Resolution;Role;Sampling;Signal Transduction;single-cell RNA sequencing;Source;Specimen;Supplementation;Testing;Therapeutic Intervention;Time;transcriptomics;treatment response;tumor;tumor growth;Tumor Immunity;tumor immunology;tumor microenvironment;tumor progression;Tumor Promotion;tumor-immune system interactions;Tumor-infiltrating immune cells;tumorigenesis;western diet;wound healing

PROJECT_TITLE: Interrogating the role of arachidonic acid metabolism in modulating the tumor immune microenvironment as a novel path to therapeutic intervention


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Bioengineering;Building Research Capacity at Institutions with Limited NIH Funding;Data Science;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD)

ORG_CITY: NORTHAMPTON

ORG_NAME: SMITH COLLEGE

PHR: PROJECT NARRATIVE A family of measurements known as wideband acoustic immittance has great potential for detecting a range of middle-ear problems with a simple noninvasive sound measurement made in the ear canal. Ultimately this approach will lead to better methods for identification of the causes of hearing loss for all ages, including newborn babies. The work proposed here expands the online database for published wideband acoustic immittance measures and uses these measurements, along with measurement validity criteria, to develop machine-learning models to differentiate between normal and abnormal ears.

PI_NAMEs: VOSS, SUSAN E (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Acoustics;Affect;Age;Air;Area;Audiology;Auditory;Biomedical Engineering;Calibration;Classification;Clinic;Clinical;clinical application;Collection;college;Communities;computer science;Conductive hearing loss;Data;data integration;Data Science;Data Set;Databases;design;Detection;Development;Diagnostic;diagnostic tool;Ear;Ear Diseases;Early Diagnosis;Education;electric impedance;Engineering;Ensure;External auditory canal;Family;Frequencies;Future;Goals;Grant;Graph;Health;Hearing;hearing impairment;hearing measurement;Infant;instrument;Intracranial Pressure;Knowledge;Label;Laboratories;Language Development;large datasets;Learning;Liquid substance;Machine Learning;machine learning model;Mathematics;Measurement;Measures;Methods;middle ear;middle ear fluid;model design;Modeling;Monitor;Neural Network Simulation;Newborn Infant;normal hearing;Otosclerosis;Pathology;Play;Publications;Published Database;Publishing;Research;response;Role;sample fixation;Science;Scientist;Series;sex;Signal Transduction;Speech Development;statistics;Students;supervised learning;Surgical Disarticulation;System;Testing;Training;Tympanometry;Ultrasonography;undergraduate education;undergraduate research experience;undergraduate student;Update;Variant;web site;Woman;Work

PROJECT_TITLE: Integrating data from a wideband acoustic immittance database to develop machine-learning models that characterize pathology in auditory measurements

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


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

ORG_CITY: PITTSBURGH

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narra+ve Adeno Associated Viruses (AAVs) are crucial to unraveling the behavioral function of neural circuits. We propose to establish a new AAV core – The BRAIN-STORRM Center at the University of Maryland Eastern Shore (UMES) – to validate and distribute a new generation of cell type specific AAVs with the potential to help unlock the mysteries of cognition and human disease. The BRAIN-STORRM Center will diversify participation in BRAIN-Initiative sponsored research by establishing an AAV hub at an HBCU, expand access to cutting edge AAVs by validating their effectiveness in the most common laboratory model organism (mice), and scale- up production and distribution channels such that novel, cell type specific AAVs can reach as many labs as possible to increase the pace, scope, and quality of neuroscientific discovery.

PI_NAMEs: HSIA, SHAOCHUNG VICTOR;STAUFFER, WILLIAM RICHARD (contact)

PROGRAM_OFFICER_NAME: KIM, DOUGLAS SUN-IL

PROJECT_TERMS: Adaptive Behaviors;adeno-associated viral vector;Animals;Behavioral;Biotechnology;Brain;BRAIN initiative;Calcium;Capsid;career;Cataloging;Catalogs;cell type;Cognition;cognitive function;Communities;Complement;Corpus striatum structure;cost;Data;Decision Making;Dependovirus;design;Effectiveness;effectiveness validation;Enhancers;Equipment and supply inventories;Feedback;Foundations;Funding;gene therapy;Generations;Genetic;genetic payload;Goals;graduate student;Halorhodopsins;human disease;Infrastructure;Injections;Jaw;Laboratories;Laboratory Animal Models;Learning;manufacture;manufacturing scale-up;Maryland;Memory;model organism;Molecular Biology Techniques;neural circuit;Neurophysiology - biologic function;Neurosciences;nonhuman primate;novel;Online Systems;operation;optogenetics;Paper;Phase;Plasmids;Production;programs;Publications;Publishing;Reagent;Recovery;Research;research and development;Resources;Rodent;Route;scale up;Science;Scientist;sensor;Serotyping;Services;Site;Specificity;Structure;Students;Technology;Technology Transfer;Testing;tool;tool development;Training;Transfer Agreement;Transgenes;Travel;undergraduate student;Underrepresented Populations;Underserved Population;Universities;Update;Validation;validation studies;vector;Viral;Viral Vector;web site;Wild Type Mouse;Work

PROJECT_TITLE: The BRAIN-STORRM Network for AAV vector manufacture and distribution

STUDY_SECTION_NAME: Special Emphasis Panel[ZMH1 ERB-E (04)]


ADMINISTERING_IC: OH

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHERS

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_CITY: IOWA CITY

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: OVERALL – PROJECT NARRATIVE The Heartland Center for Occupational Safety and Health is well positioned to address the burden of illness and injury to workers in the Midwest by preparing trainees with knowledge and experience in the discipline areas most relevant to the needs of workers in this region. As professionals, these trainees will have a long- standing positive influence on the health and well-being of workers in this region and the rest of the nation.

PI_NAMEs: O'SHAUGHNESSY, PATRICK T (contact)

PROGRAM_OFFICER_NAME: MAPLES, ELIZABETH

PROJECT_TITLE: The Heartland Center for Occupational Health and Safety Education and Research Center

STUDY_SECTION_NAME: Special Emphasis Panel[ZOH1 EHG (05)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Brain Disorders;Cerebrovascular;Dementia;Endocrine Disruptors;Foodborne Illness;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Alzheimer’s disease (AD) and AD-related dementias (ADRDs) are the leading causes of dementia and major contributors to morbidity, mortality, and healthcare costs. Exposure to environmental toxicants increases risk for AD/ADRDs and is common in disadvantaged groups, raising concerns about health disparities, socioeconomic inequities, and environmental justice. This project (responsive to RFA-AG-24-023) leverages innovative mouse models (NIA MODEL-AD) that carry human AD/ADRD genetic risk factors to generate vital resources with the goal of identifying mechanisms by which three ubiquitous metal/metalloid neurotoxicants (lead, cadmium, arsenic) impact brain health and increase risk for AD/ADRDs.

PI_NAMEs: GOLDSTEIN, LEE E. (contact);HOWELL, GARETH R;TERRITO, PAUL RICHARD

PROGRAM_OFFICER_NAME: PETANCESKA, SUZANA

PROJECT_TERMS: Acceleration;Address;Adult;Affect;Age;age related;aged;Aging;aging brain;Airborne Particulate Matter;Alleles;Ally;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid beta-Protein;Aorta;apolipoprotein E-3;apolipoprotein E-4;Arsenic;Automobile Driving;Autopsy;Behavior;biobank;Biochemical;Bioenergetics;Biological Assay;Biological Markers;Biology;Blood;Blood - brain barrier anatomy;Blood specimen;blood-based biomarker;blood-brain barrier crossing;bone;Boston;Brain;brain health;Brain Mapping;Brain Pathology;Breeding;Cadmium;Chronic;clinically relevant;Cognition;Cognitive;Cognitive deficits;Communities;Companions;Cross-Sectional Studies;Data;data resource;Dementia;dementia risk;demographics;Development;disease phenotype;Disparity;Disparity population;Doctor of Philosophy;Dose;drinking water;Elements;Environmental Exposure;environmental justice;Environmental Risk Factor;Epigenetic Process;epigenomic profiling;epigenomics;Evaluation;experience;Exposure to;Female;Food Contamination;gene environment interaction;Generations;Genes;Genetic;Genetic Diseases;genetic risk factor;Genetic Transcription;Genomics;Geography;Glial Fibrillary Acidic Protein;Glucose;Goals;Grant;Health;Health Care Costs;health disparity;Heart;High Fat Diet;Homeostasis;Human;human data;hyperphosphorylated tau;Image;Impaired cognition;in vivo imaging;Indiana;Inductively Coupled Plasma Mass Spectrometry;innovation;Kidney;Knowledge;Knowledge Portal;Late Onset Alzheimer Disease;Lead;lead exposure;life span;Link;Lung;male;Maps;Mass Spectrum Analysis;metabolomics;Metal exposure;Metals;model organism;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;multidisciplinary;multiple omics;Mus;National Institute of Environmental Health Sciences;neighborhood disadvantage;Nerve Degeneration;neurodevelopment;Neurofibrillary Tangles;neuroimaging;neuroinflammation;neuropathology;neurotoxic;Neurotoxins;North Carolina;novel;Oxidative Stress;Pathology;Pathway Analysis;Perfusion;PET/CT scan;Phenotype;Populations at Risk;Positioning Attribute;pre-clinical;Pre-Clinical Model;preclinical study;prenatal;Process;protein expression;Protocols documentation;Race;Research;Research Design;Resolution;Resources;response;Risk;Risk Factors;Role;Route;sedentary lifestyle;Senile Plaques;sex;socioeconomic disparity;socioeconomics;Structure;synergism;tau Proteins;The Jackson Laboratory;Tissue Banks;Toxic Environmental Substances;toxic metal;toxicant;Toxicant exposure;Trace Elements;Universities;Variant;Vascular Diseases

PROJECT_TITLE: Leveraging novel mouse models to investigate toxic metal exposures on brain aging and Alzheimer's disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-P (M3)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Diabetes;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Our project addresses the need for “diversity and more representative cohorts” in the NIA/AA Revised Clinical Criteria for AD. In addition, our project is responsive to RFA-AG-24-022 by contributing a multidisciplinary team of experts in environmental science, molecular mechanisms, diabetes, and AD/ADRD that will conduct comprehensive targeted and untargeted measurement of environmental toxicants, and comprehensive examination of intermediate molecular mechanisms, in relation to AD/ADRD.

PI_NAMEs: CARDENAS, ANDRES ;FLEISCH, ABBY ;LUCHSINGER, JOSE ALEJANDRO (contact);MILLER, GARY W;STARLING, ANNE ;TEMPROSA, MARINELLA

PROGRAM_OFFICER_NAME: ANDERSON, DALLAS

PROJECT_TERMS: Address;adjudication;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid;apolipoprotein E-4;Biological;Biological Markers;Biological Specimen Banks;Brain imaging;brain magnetic resonance imaging;causal model;Cerebrovascular Disorders;Chromatography;Clinical;Cognition Disorders;Cognitive;cognitive reserve;cognitive testing;cohort;Cohort Studies;Coupled;Data Set;Dementia;dementia risk;Detection;Diabetes Mellitus;diabetes prevention program;Diagnosis;Digit structure;Disparity;DNA Methylation;Elements;environmental chemical;environmental chemical exposure;Environmental Health;Environmental Impact;Environmental Science;Ethnic Origin;Ethnic Population;Etiology;Exposure to;extracellular vesicles;Female;Funding;Gases;Glial Fibrillary Acidic Protein;Goals;Heavy Metals;high risk;Impaired cognition;Individual;insulin signaling;Isotopes;Leukocytes;Light;Link;Liquid substance;Mass Spectrum Analysis;Measurement;Measures;metabolome;metabolomics;Metals;MicroRNAs;mild cognitive impairment;Modification;Molecular;multidisciplinary;National Institute on Aging;Nerve Degeneration;neurofilament;neuroinflammation;Neurons;neuropathology;Non-Insulin-Dependent Diabetes Mellitus;Outcome;Outcome Study;Participant;Pathologic;Peripheral;Persons;Pesticides;Phase;Phenotype;Plasma;Poly-fluoroalkyl substances;Positron-Emission Tomography;Prediabetes syndrome;prospective;Race;racial population;Research;Resolution;response;Role;sex;small molecule;Solid;Spanish/English;statistics;substance use;Syndrome;Systems Biology;tandem mass spectrometry;Testing;Toxic Environmental Substances;Toxicant exposure;Urine;Verbal Learning;β-amyloid burden

PROJECT_TITLE: Impact of environmental toxicants on AD and ADRD risk in the Diabetes Prevention Program Outcomes study AD/ADRD project

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-P (M2)]


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: Solid tumors are difficult to treat with cell-based immunotherapies due to the immunosuppressive environment created by the tumor mass, in part caused by the secretion of byproducts of dysregulated tumor metabolism. We have identified that succinate, a key metabolite that accumulates in tumors and is secreted into the tumor microenvironment, promotes the induction of Tregs from CD4+ T cells, and propose to further test the effects of succinate on enhancing the suppressive phenotype of Tregs that have infiltrated the tumor, driving the suppression of effector CD8+ T cell anti-tumor responses. Targeting succinate signaling is a promising therapeutic strategy to alleviate Treg-mediated suppression of CD8+ effector T cells and enhance anti-tumor immunity and improve response to immunotherapies.

PI_NAMEs: KINSELLA, SINÉAD  (contact)

PROGRAM_OFFICER_NAME: CARDONE, MARCO

PROJECT_TERMS: antagonist;antigen-specific T cells;Antigens;Antitumor Response;Attenuated;Automobile Driving;Avidity;Binding;Bioenergetics;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;cell killing;Cell Physiology;Cell surface;Cells;Cellular immunotherapy;Clinical;Combined Modality Therapy;Communication;CRISPR/Cas technology;Data;design;Development;effector T cell;Environment;extracellular;Extracellular Space;Frequencies;Gatekeeping;Genes;Glucose;Helper-Inducer T-Lymphocyte;humanized mouse;Hypoxia;Immune;Immunocompetent;Immunosuppression;Immunotherapy;improved;in vivo;Infiltration;innovation;Intercellular Fluid;interstitial;Knock-out;lipid metabolism;Malignant Neoplasms;Mediating;Melanoma;melanoma-associated antigen-A1;Membrane;Metabolic;Metabolic dysfunction;Mitochondria;Modeling;Molecular;mouse model;Mus;Mutation;Myelogenous;Myeloid Cells;neoplasm immunotherapy;new therapeutic target;novel;Nutrient;Outcome;Peripheral;Phenotype;preclinical study;preferentially expressed antigen in melanoma;pressure;Production;Proliferating;receptor;Receptor Activation;Recurrent tumor;Regulatory T-Lymphocyte;response;Role;Signal Transduction;Signaling Molecule;small molecule;small molecule inhibitor;Solid Neoplasm;success;Succinate Dehydrogenase;Succinates;T cell differentiation;T cell infiltration;T-Lymphocyte;TCR Activation;Testing;Therapeutic;therapeutic evaluation;Thymus Gland;translatable strategy;treatment response;tumor;Tumor Antigens;Tumor Burden;Tumor Immunity;tumor metabolism;tumor microenvironment;Tumor-Derived;tumor-immune system interactions

PROJECT_TITLE: Targeting Tregs in the solid tumor microenvironment by modulating metabolite signaling

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 RTRB-S (M2)]


FUNDING_MECHANISM: SBIR-STTR RPGS

ORG_CITY: ATHENS

ORG_NAME: NYTRICX INC.

ORG_STATE: GA

PHR: NARRATIVE Nytricx, Inc. has recently recruited and hired a US Citizen and minority candidate, Ms. Pravalika Irukulla, BS, MS in Biological Engineering to perform the laboratory research work described in the funded Nytricx Phase II STTR (Award Number: 2R42HL149595-02A1, project period 05/01/2020 to 07/31/2025). The title of the funded application is “Ultra-low Fouling and Anti- infective and Anti-thrombotic Nitric Oxide Releasing Intravascular Catheters.”

PI_NAMEs: SHEBUSKI, RONALD J. (contact)

PROGRAM_OFFICER_NAME: LIU, SONGTAO

PROJECT_TERMS: Anti-Bacterial Agents;Anti-Infective Agents;antimicrobial;Applications Grants;Award;Biomedical Engineering;Blood coagulation;Blood Vessels;Catheters;commercialization;Crowding;Employment;Equipment and supply inventories;fabrication;Funding;Gases;In Vitro;in vivo;Infection;innovation;Kinetics;Laboratory Research;Marketing;medical complication;Minority;National Heart, Lung, and Blood Institute;Nitric Oxide;Nitric Oxide Donors;Occupations;Phase;Polymers;Postdoctoral Fellow;recruit;Research;Small Business Technology Transfer Research;Surface;Thrombosis;thrombotic;Work

PROJECT_TITLE: Ultra-low Fouling and Anti-infective and Anti-thrombotic Nitric Oxide Releasing Intravascular Catheters


NIH_SPENDING_CATS: Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Pain Research;Patient Safety;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: Newborns in the neonatal intensive care unit (NICU) undergoing invasive procedures or surgeries are frequently exposed to prolonged pain, postoperative complications, and human suffering because of the major difficulties in measuring neonatal pain, inconsistent and ineffective pain management, and delayed pain treatments due to nursing workload. Our proposed research aims to develop an AI-driven automated system to objectively and continuously measure newborn pain and pain sensitization based on several biomarkers, and when detected, to send their pain alarms to bedside nurses in real-time. The proposed neonatal pain monitoring system allows us to create therapeutic strategies that minimize pain, stress, and total opioid doses given during the post-operative care of newborns, thereby improving their clinical and post-surgical outcomes.

PI_NAMEs: ANAND, KANWALJEET S;HO, THAO ;PRESCOTT, STEPHANIE ;SUN, YU  (contact)

PROGRAM_OFFICER_NAME: ARUDCHANDRAN, RAMACHANDRAN NMN

PROJECT_TERMS: Absence of pain sensation;Acute;Acute Pain;Analgesics;behavioral response;Biochemical;Biological Markers;biomarker signature;Brain;brain dysfunction;Brain Stem;brain volume;burnout;Caring;Catabolism;central sensitization;Clinical;Clinical Trials Design;Code;Cognitive deficits;Color;Coupled;Crying;Data;Data Collection;Decision Making;Development;Discipline of Nursing;Dose;efficacy testing;Enrollment;Event;executive function;experience;Exposure to;Facial Expression;feeding;Goals;Growth;Health Care Costs;Hospital Costs;Hospitalization;Hospitals;Hour;Human;Hydrocortisone;improved;Individual;Infant;Infant Care;Inflammation;innovation;Lead;Length of Stay;Long-Term Effects;Measures;Mechanical ventilation;Medical History;Medical Records;Medication Errors;Medication Management;Memory impairment;Modeling;Monitor;Motion;multidisciplinary;National Institute of Child Health and Human Development;Neonatal;neonatal care;Neonatal Intensive Care Units;neonate;Newborn Infant;non-opioid analgesic;Nonpharmacologic Therapy;novel;novel therapeutics;Nurses;Operative Surgical Procedures;Opioid;opioid exposure;opioid use;Organ;Outcome;Pain;Pain intensity;Pain management;Pain Measurement;pain outcome;pain processing;pain reduction;pain score;patient population;Pediatric Surgical Procedures;Pharmaceutical Preparations;Pharmacotherapy;Phase;Physiological;Population;Postoperative Care;Postoperative Complications;Postoperative Pain;Postoperative Period;prevent;primary outcome;Procedures;Process;prospective;Protocols documentation;Provider;Publishing;Quality of Care;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Records;Recovery;Regimen;Research;Role;Safety;Salivary;secondary outcome;sedative;sensory stimulus;Short-Term Memory;side effect;Signal Transduction;skills;sound;Specificity;Spinal Cord;Standardization;Stress;Sucrose;supplemental oxygen;Surgical Injuries;Surgical Management;surgical pain;Surveys;System;Testing;Therapeutic;Time;tool;transmission process;Trauma;visual-motor integration;wireless;Workload

PROJECT_TITLE: Developing AI-Driven Pain Intensity and Pain Sensitization Biomarker Signatures to Optimize Neonatal Pain Management

STUDY_SECTION_NAME: Special Emphasis Panel[ZNS1 SRB-R (19)]


NIH_SPENDING_CATS: Asthma;Genetics;Lung;Pediatric

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

ORG_STATE: OH

PHR: NARRATIVE  It remains difficult to effectively alleviate asthmatic symptoms and limit disease progression in children with severe asthma. While corticosteroids can be effective, children with severe asthma develop corticosteroid insensitivity or resistance making their disease difficult to manage. The goal of this proposal is to understand how inflammation promotes corticosteroid resistance in the context of severe pediatric asthma. These studies are also aimed to assess the potential for therapeutic strategies to improve corticosteroid sensitivity.

PI_NAMEs: BRITT, RODNEY  (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: Adrenal Cortex Hormones;Adult;airway hyperresponsiveness;airway inflammation;airway obstruction;airway remodeling;Allergens;allergic airway inflammation;Asthma;asthmatic;ATAC-seq;Bioinformatics;Biological;Cells;Child;Childhood;Childhood Asthma;Chromatin;Chromatin Structure;Chronic;Clinical;Complex;cytokine;Data;Deposition;Development;Disease;Disease Progression;DNA;Dose;Exhibits;Exposure to;Extracellular Matrix;Functional disorder;Genes;Genetic Transcription;Glucocorticoid Receptor;Goals;Health;healthcare burden;Histology;Human;human model;Hypertrophy;Image;Immune;immune cell infiltrate;Immune Cell Suppression;improved;Infiltration;Inflammation;Inflammatory;Inhalation;inhibitor;Interferon Type II;Knockout Mice;Lung;Lymphocyte;Lymphocytic Infiltrate;Mediating;Molecular;Morbidity - disease rate;mouse model;Mus;Muscle function;muscular structure;MYH11 gene;novel;novel therapeutic intervention;Nuclear Translocation;p65;Pathway interactions;Phosphorylation;Post-Translational Regulation;Production;Proliferating;receptor;Regulatory Pathway;Reporting;Resistance;resistance gene;respiratory examination;respiratory smooth muscle;Role;Side;Signal Pathway;Smooth Muscle;Steroid Resistance;Steroid therapy;Steroids;Symptoms;synergism;Testing;Therapeutic;TNF gene;Transcriptional Regulation;transcriptome sequencing

PROJECT_TITLE: Airway Structural Cells and Corticosteroid Resistance in Asthma

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


NIH_SPENDING_CATS: Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Natural Products

ORG_CITY: PROVO

ORG_NAME: BRIGHAM YOUNG UNIVERSITY

PHR: Project Narrative  This project involves the the discovery of new synthetic methods and their application to constructing peptide natural products. Most of the targeted peptides are biologically active, and some have potent anticancer activity. With the potential of spawning new therapeutic peptides for cancer and other diseases, this project is highly relevant to public health and to the mission of the NIH.

PI_NAMEs: CASTLE, STEVEN L (contact)

PROJECT_TERMS: Acceleration;Acids;Alkylation;Amides;analog;anti-cancer;anticancer activity;Antineoplastic Agents;Area;Back;Binding;bioactive natural products;Biology;carboxylate;Chemicals;Complex;Coupling;Cyclic Peptides;Dehydration;design;Development;Disease;drug candidate;epimerization;FDA approved;fighting;forging;frontier;Funding;Goals;Health;Human;Hybrids;improved;Industrialization;innovation;Investigation;Left;Libraries;Ligation;Malignant Neoplasms;Mediating;Medicine;Methods;Methylation;Mission;Modeling;Molecular Probes;natural product inspired;Natural Products;novel;novel therapeutics;Organic Synthesis;Outcome;Outcome Study;Patients;peptide drug;peptide natural products;Peptide Synthesis;Peptides;Periodicity;Pharmaceutical Chemistry;Physical condensation;Plant Resins;prevent;Process;process optimization;Protocols documentation;Public Health;Research;Sampling;Serine;Solid;stable plasma protein solution;Structure;T-20;Testing;Thioamides;tool;United States National Institutes of Health;Work

PROJECT_TITLE: New Methods for Synthesizing Bioactive Peptides


ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: Narrative Overall The mission of the Great Lakes Center for Occupational Health and Safety is to improve, promote, and maintain the health of workers and communities through innovative and interdisciplinary activities such as training future OSH professionals, fostering networks and partnerships across industries and community and expanding the scope of current research in OSH.

PI_NAMEs: BUCHANAN, SUSAN NATHALIE (contact)

STUDY_SECTION_NAME: Special Emphasis Panel[ZOH1 EHG (06)]


NIH_SPENDING_CATS: Bioengineering;Building Research Capacity at Institutions with Limited NIH Funding;Genetics;Human Genome

ORG_CITY: KEARNEY

ORG_NAME: UNIVERSITY OF NEBRASKA KEARNEY

ORG_STATE: NE

PHR: PROJECT NARRATIVE Within the human genome, structural variations change more base pairs than point mutations, and those variations may lead to different diseases. However, long DNA molecules aid in assembling these large variations by spanning the length of the variation. This research aims to develop a system that will produce long molecules that can be analyzed with sequencing or physical mapping to find these larger variations.

PI_NAMEs: KOUNOVSKY-SHAFER, KRISTY  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: 3D Print;Acrylamides;Base Pairing;Biological Sciences;Cells;Charcot-Marie-Tooth Disease;Chromosome abnormality;Chromosomes;Complex;Copy Number Polymorphism;Cytolysis;design;Detection;Development;Devices;Diffusion;Disease;disease heterogeneity;Disease susceptibility;DNA;electric field;Escherichia coli;Gel;Gene Expression;Genes;Genetic Diseases;genetic information;genetic variant;Genome;genome analysis;Genomic Segment;Goals;Haplotypes;Human Genome;Huntington Disease;improved;innovation;Length;Link;Liquid substance;Malignant Neoplasms;Maps;meetings;Methods;Modification;novel;Optics;Oral;Outcome;Parkinson Disease;Peer Review;Phase;physical mapping;Physiologic pulse;Point Mutation;posters;prevent;Productivity;Publications;Pulsed-Field Gel Electrophoresis;Qualifying;reconstruction;Regulatory Element;Research;Saccharomyces cerevisiae;Sampling;Sepharose;Side;System;Testing;undergraduate student;Variant;Work;Writing

PROJECT_TITLE: Development of a system to protect and concentrate large DNA for genome analysis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-Y (82)]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: Springfield

ORG_NAME: OREGON RESEARCH INSTITUTE

ORG_STATE: OR

PHR: PROJECT NARRATIVE The COVID-19 pandemic has had a detrimental effect on mental health, especially for emerging adults. Utilizing the longitudinal Early Steps Multisite prevention trial of diverse, low-income families (N=731) from three geographic areas across the United States, we plan to take advantage of an 18-year-long prospective dataset in conjunction with new mental health assessments to examine risk and resilience factors for at-risk emerging adults, transitioning from adolescence to adulthood in the context of a pandemic. With genotyping on an extensive contemporary array, prospective data on experiences of discrimination, and neighborhood and community risk/resilience factors, we plan to examine direct, interactive, and cascading effects on mental health outcomes, and the long-term preventive effects of the Family Check-Up, in the context of growing up in poverty, and, more recently, the pandemic.

PI_NAMEs: BROWN-IANNUZZI, JAZMIN ;LEMERY-CHALFANT, KATHRYN ;SHAW, DANIEL S;WESTLING, ERIKA  (contact)

PROGRAM_OFFICER_NAME: ROONEY, MARY

PROJECT_TERMS: 2019-nCoV;Adolescence;Adult;Age;age group;American;Anxiety;Attention;Behavioral;biological sex;Buffers;caucasian American;Characteristics;checkup examination;Child;clinical diagnostics;Communities;coping;Coronavirus;COVID-19;COVID-19 pandemic;Data;Data Set;design;Deterioration;Development;dietary supplements;Disease;early childhood;Early Intervention;Ecology;Economics;emerging adult;emerging adulthood;Emotional;Environmental Risk Factor;ethnic disparity;ethnic diversity;ethnic identity;ethnic minority;Ethnic Origin;Ethnic Population;experience;Exposure to;Family;Future;Gender Identity;Genetic;Genetic Predisposition to Disease;Genetic Risk;genetic testing;Genotype;Geographic Locations;Geography;Glean;health assessment;health inequalities;High Prevalence;higher education;Home;Individual;Inequality;Infant;Informal Social Control;Institutional Racism;Intervention;intervention effect;Interview;Link;Long-Term Effects;Longitudinal Studies;lower income families;Mediating;Mental Depression;Mental Health;Minority Groups;Neighborhoods;Outcome;pandemic disease;pandemic potential;pandemic stress;Parents;Participant;perceived discrimination;physical conditioning;polygenic risk score;Poverty;pre-pandemic;Predictive Factor;prevent;Prevention;Prevention trial;Preventive;Problem behavior;prospective;protective effect;protective factors;Psychoses;Public Health;Race;racial discrimination;racial disparity;racial diversity;racial minority;racial population;racism;Randomized;recruit;Reporting;Research;resilience;resilience factor;Risk;Risk Factors;risk mitigation;Rural;Sampling;Shock;Site;social culture;social determinants;social factors;Social Identification;Social isolation;Socialization;Societies;sociocultural determinant;sociodemographics;socioeconomics;stressor;suburb;suicidal;Suicide;Support System;Surveys;Symptoms;Testing;Time;transition to adulthood;United States;Vocation;Woman;young adult

PROJECT_TITLE: Preventing Adult Mental Health Problems from Early Childhood in the Contexts of Genetic Susceptibility, Poverty, Racism, and the COVID-19 Pandemic

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


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;Prevention

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Clonal hematopoiesis (CH) is associated with several age-related diseases including cardiovascular disease (CVD) and Alzheimer's disease (AD) but the mechanisms driving CH progression and its impact on CVD and AD are largely undefined. Our central hypothesis is that inherited, and lifestyle risk factors impact CH evolution through immune dysregulation and that this, in turn, determines the development of disease. We will leverage existing data from large-scale biobanks alongside longitudinal CH and proteomic profiling in cohorts with rich phenotyping to determine (1) the impact of lifestyle and inherited risk factors on CH evolution, (2) the pathways that mediate CH evolution and (3) the pathways that mediate the association between CH with CVD and AD.

PI_NAMEs: BOLTON, KELLY LEIGH (contact)

PROGRAM_OFFICER_NAME: RAGHAVACHARI, NALINI

PROJECT_TERMS: adjudication;adverse outcome;age related;age-related disease;Aging;Alzheimer's Disease;Alzheimer's disease risk;Anti-Inflammatory Agents;Automobile Driving;Behavior;biobank;Biological;Biological Response Modifiers;Biology;Cardiovascular Diseases;cardiovascular disorder risk;Cause of Death;Cell Physiology;Cells;Cessation of life;Chronic;Cognition;cohort;Development;Diet;disability;Disease;Disease Outcome;Disease Progression;Elderly;Equilibrium;Evolution;fitness;follow-up;Follow-Up Studies;Goals;Health Professional;healthy aging;Hematopoiesis;Hematopoietic stem cells;Human;Immune;improved;Individual;individualized prevention;Inflammation;Inflammatory;Inherited;large scale data;Life;Life Cycle Stages;Life Style;Longitudinal Studies;Longterm Follow-up;Measurement;Measures;Mediating;Mendelian randomization;middle age;modifiable risk;Mutate;Mutation;new therapeutic target;Obesity;Outcome;Participant;Pathway interactions;Phenotype;physical inactivity;Plasma;Plasma Proteins;Pre-Clinical Model;premature;prevent;Prevention strategy;Prospective cohort;Proteins;Proteomics;Research;Risk;Risk Factors;risk prediction;Sampling;Signal Transduction;Smoking;Testing;unhealthy lifestyle;United States;Work

PROJECT_TITLE: The impact of inherited and modifiable risk factors on clonal hematopoiesis and age-related disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZAG1 ZIJ-I (M3)]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: American Indian or Alaska Native;Arctic;Behavioral and Social Science;Clinical Research;Complementary and Integrative Health;Harm Reduction for Substance Misuse;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Neurosciences;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Prevention;Racial and Ethnic Minority Health Research;Substance Misuse;Substance Misuse Prevention;Suicide;Suicide Prevention

ORG_CITY: TOPPENISH

ORG_NAME: YAKAMA TRIBAL COUNCIL D/B/A CONFEDERATED TRIBES AND BANDS OF THE YAKAMA NATION

PI_NAMEs: GEORGE, NACHYA ;SALUSKIN, KATHERINE R (contact)

PROGRAM_OFFICER_NAME: OUDEKERK, BARBARA ANN

PROJECT_TERMS: Acute;addiction;Address;Adult;Affect;Agreement;Alaska Native;Applications Grants;Area;Articulation;authority;Awareness;Back;Behavior;behavioral health;Binding;Caring;Cause of Death;Cessation of life;Client;Clinic;Clinical;clinical care;Clinical Services;Collaborations;Collection;Communities;community academic partnership;Community Actions;Community Health Aides;Community Workers;cost;Country;Coupled;Crisis Intervention;curriculum enhancement;Custom;Data;data infrastructure;data management;data sharing;Decision Making;design;Development;Diffusion;Drug usage;Educational Curriculum;Effectiveness;Emergency Situation;Ensure;evidence base;Exhibits;experience;Family member;family support;Feedback;Fentanyl;first responder;Funding;Future;Goals;Guidelines;Harm Reduction;Health;health data;Health Personnel;Health Promotion;Health Services;Health Services Research;help-seeking behavior;high risk;Hour;human subject protection;implementation strategy;improved;Indigenous;Individual;Infrastructure;innovation;Inpatients;Institutional Review Boards;Intervention;Intervention Trial;Interview;Inupiat;Investments;Knowledge;Lead;Leadership;Learning;Legal;Lived experience;Measures;meetings;member;Mental Health;Michigan;Modeling;Naloxone;novel;Opioid;opioid epidemic;opioid mortality;opioid overdose;opioid use;Outcome;Overdose;overdose death;overdose prevention;Ownership;Parents;Participant;Personal Satisfaction;Persons;Pharmaceutical Preparations;Phase;Policies;Preparation;prevent;Prevention;Prevention approach;Prevention Research;Procedures;Professional counselor;programs;Publications;Readiness;Recommendation;Recovery;Reporting;Research;Research Activity;research data dissemination;Research Infrastructure;Research Project Grants;Risk;Risk Reduction;screening;Self Determination;Self Efficacy;Series;service programs;service providers;Services;skills;Social support;Structure;substance misuse;substance use;suicidal morbidity;suicidal risk;Suicide;Suicide prevention;suicide rate;teacher;Teenagers;Testing;Time;tool;Training;Translating;tribal community;Tribal Council;tribal leader;tribal member;tribal Nation;Tribes;Trust;United States National Institutes of Health;Universities;Washington;Well in self;Wellness Program;Work;Yakama Indian;Yup'ik

PROJECT_TITLE: Yakama Nation: Native Collective Research Effort to Enhance Wellness Program

STUDY_SECTION_NAME: Special Emphasis Panel[ZTR1 OTHR-6 (01)]


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative This pilot, short-term (4 weeks) phase II single-center study will test the safety and efficacy of Fimepinostat in the treatment of patients with de novo, persistent, and/or recurrent CD recruited at the University of California, Los Angeles. The trial will examine two different doses/schedules of Fimepinostat in two subject groups to determine the most effective and least toxic dose regimen for subsequent, larger clinical trials.

PI_NAMEs: HEANEY, ANTHONY P (contact)

PROGRAM_OFFICER_NAME: FERMAGLICH, LEWIS

PROJECT_TITLE: Fimepinostat, Combination HDAC and Pi3-kinase Inhibitor Tumor-Directed Therapy for Cushing Disease (IND 168501 - 07/31/2023)

STUDY_SECTION_NAME: Special Emphasis Panel[ZFD1 OC-S (01)]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: Boulder

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Narrative We are using a basic biology approach grounded in host-pathogen interactions to discover new compounds that disrupt the infection process. This represents the earliest possible stage of antibiotic discovery and relies upon bacterial cell physiology, in vitro, and in vivo infection models to identify workable new research directions.

PI_NAMEs: DETWEILER, CORRELLA S (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Antibiotics;Bacteria;Biology;Cell Physiology;Grant;Hand;In Vitro;in vivo;Infection;Macrophage;Mentors;Modeling;parent grant;pathogen;pathogenic bacteria;Process;Research;Research Personnel;tool

PROJECT_TITLE: Infection-Dependent Vulnerabilities of Gram-negative Bacterial Pathogens


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: HINES

ORG_NAME: EDWARD HINES JR VA HOSPITAL

PHR: Glaucoma remains a leading cause of irreversible blindness. Within 20 years, glaucoma will affect nearly 112 million people worldwide. Ocular hypertension has been identified as a primary risk factor for primary open angle glaucoma (POAG), the most common form of glaucoma. However, many POAG patients present with normal ocular tension, often referred to as normal-tension glaucoma. While the cause of normal-tension glaucoma remains unclear, recent studies implicate a role for a pressure gradient differential across the optic nerve head in affected patients. Here, we will test this thesis using guinea pigs as potential animal model of human normal-tension glaucoma. Successful completion of the proposed study will validate recent findings and establish the guinea pig as a clinically useful animal model in which to study human ocular disorders, including normal-tension glaucoma. Novel findings produced by this study will elucidate the role pressure gradient differential across the lamina cribrosa play in the development of this insidious disorder.

PI_NAMEs: STUBBS, EVAN B. (contact)

PROJECT_TERMS: Address;Affect;age related;aged;Aging;American;Anatomy;Animal Model;Blindness;Cavia;Cerebrospinal Fluid Pressure;Cerebrospinal fluid shunts procedure;Chronic;Clinical;clinically relevant;design verification;Development;Disease;Economic Burden;Electrons;Electroretinography;Etiology;Exhibits;experimental study;Eye diseases;Functional disorder;Funding;Glaucoma;Goals;Healthcare Systems;Histologic;Human;human model;in vivo;Individual;Laboratories;micrography;military veteran;Modeling;morphometry;Multicenter Studies;Neurodegenerative Disorders;Neurons;Neuropathy;Normal Range;novel;novel therapeutic intervention;Ocular Hypertension;Optic Disk;optic nerve disorder;Optics;palliative;Patients;Pattern;Peritoneal;Persons;Physiologic Intraocular Pressure;Pilot Projects;Play;Population;pressure;Prevalence;Primary Open Angle Glaucoma;prospective;Quality of life;Randomized;Retina;Retinal Ganglion Cells;Review Literature;Risk Factors;Role;socioeconomics;targeted treatment;Testing;Time;United States Department of Veterans Affairs;Validation;validation studies;Veterans

PROJECT_TITLE: Translamina Cribrosa Pressure Gradient Model of Normal Tension Glaucoma


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

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_STATE: PA

PHR: PROJECT NARRATIVE This project will increase the understanding of the evolutionary predictability of antimicrobial resistance for the high-priority nosocomial pathogen, Acinetobacter baumannii. Using clinical isolates, the research proposed in this application will increase translational predictive measures of resistance adaptability, demystify the genotype- phenotype map of virulence and resistance associated phenotypes, and clarify the genetic level to which resistance evolution is predictable. The results will guide future treatment optimization and be applicable to other multidrug resistant bacterial pathogens.

PI_NAMEs: ROKES, ALECIA BARBARA (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Acinetobacter baumannii;Address;Affect;Antibiotics;Antimicrobial Resistance;Award;Awareness;Bacterial Infections;Biological Assay;Biology;career;Clinical;Clinical Data;clinically relevant;Collection;Comparative Genomic Analysis;comparative genomics;CRISPR interference;Data Set;Doctor of Philosophy;Drug Efflux;drug modification;Drug resistance;Drug Targeting;Engineering;Environment;Evolution;experimental study;extensive drug resistance;Fellowship;fighting;fitness;Foundations;Future;Genes;Genetic;genetic resistance;Genome;genome sequencing;Genotype;global health;Goals;Growth;Hospitals;improved;Infection;innovation;knock-down;Knowledge;Laboratories;Maps;Measurement;Measures;Medical center;Mentorship;Microbial Biofilms;Molecular;Monitor;Multi-Drug Resistance;multi-drug resistant pathogen;Multiple Bacterial Drug Resistance;Mutation;Natural Selections;pan-genome;pathogen;pathogenic bacteria;Pathway interactions;Patient-Focused Outcomes;Pattern;personalized therapeutic;Pharmaceutical Preparations;Phenotype;Phylogenetic Analysis;Phylogenetic Pattern;Population;predictive tools;Predisposition;Presbyterian Church;Prevention;Production;Protocols documentation;Recording of previous events;Research;Resistance;Resistance profile;resistant strain;Ribosomes;Role;Rotation;Scientist;Shapes;Stress;Students;Testing;tigecycline;Training;trait;treatment optimization;treatment strategy;undergraduate student;Universities;Virulence;whole genome;Work

PROJECT_TITLE: Using strain history to improve prediction of the evolution of antimicrobial resistance in Acinetobacter baumannii


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: AMHERST

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: Narrative This proposal will investigate how the human pathogen Cryptococcus neoformans senses host body temperature, responds, and establishes an infection leading to disease. The goal of this work is to better understand the molecular mechanisms by which C. neoformans communicates stress signals to the protein synthesis machinery, the ribosome. Elucidation of these mechanisms may allow for process to be targeted to prevent successful infection.

PI_NAMEs: GOICH, DAVID  (contact)

PROJECT_TERMS: Acute;Advisory Committees;Ascomycota;Attenuated;Biogenesis;biological adaptation to stress;Biological Assay;Biotin;Biotinylation;Body Temperature;Buffers;candidate identification;Cessation of life;Communication;Compensation;Complement;Cryptococcus neoformans;Data;Defect;design;Development;Disease;Educational workshop;EIF-2alpha;Equipment;experimental study;follow-up;Fungi Model;Genetic Transcription;Goals;human pathogen;Immune system;improved;Infection;insight;Knock-out;Knowledge;Ligase;liquid chromatography mass spectrometry;Macrophage;MAP Kinase Modules;Maps;Masks;Mediating;Messenger RNA;mimetics;Modeling;Molecular;mouse model;mRNA Stability;Mus;mutant;Northern Blotting;Nucleic Acid Binding;Nutrient;opportunistic pathogen;Osmosis;Output;Oxidative Stress;p38 Mitogen Activated Protein Kinase;Pathogenesis;pathogenic fungus;Pathogenicity;Pathway interactions;Persons;Phenotype;Phosphorylation;Phosphotransferases;Play;polysome profiling;prevent;Process;Protein Biosynthesis;Proteins;Regulation;Regulatory Pathway;Regulon;Repression;Research Personnel;Research Training;response;Ribosomal RNA;ribosome profiling;Ribosomes;Role;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Site;skills;Stress;stress tolerance;stressor;symposium;Temperature;Testing;Training;training opportunity;Transcript;transcription factor;Transcriptional Regulation;transcriptome;transcriptome sequencing;Translating;translation factor;Translation Initiation;Translational Regulation;Translational Repression;translatome;Universities;uptake;Virulence;Work

PROJECT_TITLE: The role of C. neoformans Hog1 and its effectors in translatome reprogramming


ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: Narrative: Infections from pathogenic bacteria and viruses like SARS-CoV-2 cause alternative responses in the adaptive immune system that can alter the severity of the infection. Our studies will identify a component of these responses, memory B cells, to link as a network that controls humoral immunity in response to infection by creating superior protection. This research will lead to improved vaccine developments and memory B cell therapies.

PI_NAMEs: WIGGINS, KEENAN  (contact)

PROJECT_TERMS: 2019-nCoV;Adaptive Immune System;Address;Antigens;B cell differentiation;B cell therapy;B-Cell Activation;B-Cell Development;B-Lymphocyte Subsets;B-Lymphocytes;BACH2 gene;BCL6 gene;Binding;Biological Assay;CCR6 gene;CD4 Positive T Lymphocytes;CD44 gene;CD80 gene;Cell Communication;Cell Cycle Progression;Cell Differentiation process;cell motility;Cell Reprogramming;Cell Separation;Cell Survival;Cells;Chromatin;Complex;CXCR3 gene;Development;DNA Methylation;DNA Sequence;Enhancers;Environment;Epigenetic Process;Gene Expression;Gene Modified;gene repression;Genes;Genetic Transcription;histone methyltransferase;histone modification;Histones;Homologous Gene;Humoral Immunities;Immune system;Immunoglobulin-Secreting Cells;improved;in vivo;Infection;Influenza;influenzavirus;Knock-out;Learning;Link;Longevity;lymph nodes;Lymphatic System;Maps;Mature B-Lymphocyte;Mediating;Memory B-Lymphocyte;migration;Modification;Molecular;mouse model;Mus;Nucleosomes;Organism;pathogen;pathogenic bacteria;pathogenic virus;Pathway interactions;Phenotype;plasma cell differentiation;Play;Polycomb;Population;Process;Proteins;receptor;recruit;Regulation;Research;Resources;response;Role;Severities;Signal Pathway;Signal Transduction;Signaling Protein;Spleen;Structure of germinal center of lymph node;T-Cell Development;Tail;Testing;TLR7 gene;transcription factor;transcriptomics;Untranslated RNA;Vaccination;vaccine development;Vaccines;Work

PROJECT_TITLE: Differentiation of memory B cells requires EZH2 and epigenetic remodeling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07B-U(20)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Depression;Drug Abuse (NIDA only);Mental Health;Neurosciences;Substance Misuse

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Project Narrative: Neurons in the ventral tegmental area (VTA) that express the neuropeptide, tachykinin receptor 3 (Tacr3), are a distinct subpopulation of dopamine-producing neurons that promote reward reinforcement behavior. However, the intracellular signaling pathways that act downstream of this Gq-protein coupled receptor to regulate this behavior are unresolved. This proposal will investigate the role of transient receptor potential canonical type 6 channels in regulating the physiology and function of VTA-Tacr3 neurons, which will provide important insights into the therapeutic potential of this understudied ion channel in the central nervous system.

PI_NAMEs: BERNSTEIN, MOLLIE XIAOQI (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Action Potentials;Adult;Agonist;anti-depressive agents;Bathing;Behavior;Borates;Calcium;Calcium ion;Calcium Signaling;cell type;Cells;Central Nervous System;channel blockers;comparison control;Control Groups;Coupled;CRISPR/Cas technology;Decision Making;Depressive disorder;discounting;Dopamine;dopaminergic neuron;Electrophysiology (science);Exhibits;experimental group;experimental study;Fluorescence;G alpha q Protein;Genes;Genetic Markers;genetic technology;Goals;hyperforin;Hypericum perforatum;Hypothalamic structure;Image;in vivo;insight;Ion Channel;KISS1 gene;Learning;Link;loss of function;Mental Depression;Mental disorders;Midbrain structure;motivated behavior;Motivation;Mus;Mutate;Nervous System Disorder;Neurons;Neuropeptide Receptor;Neuropeptides;patch clamp;Pathway interactions;Physiology;Play;Population;Probability;Psychological reinforcement;receptor;Receptor Signaling;reuptake;Rewards;Role;Schizophrenia;Serotonin;Signal Pathway;Signal Transduction;Slice;Stimulus;Substance Use Disorder;TACR3 gene;Testing;Therapeutic;Transgenic Mice;Ventral Tegmental Area

PROJECT_TITLE: Determining the function of TRPC6 channels in a subpopulation of VTA dopamine neurons


ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE The delicate balance between pro- and anti- inflammatory programs is a critical prognostic factor following stroke. This project will investigate how the gut microbiota controls stroke outcome through action on dendritic cells, which provide a link between innate and adaptive immunity. Such studies are essential to understand how the microbiota, and diet which is closely linked, can affect susceptibility to poor stroke outcome and how implicated immune pathways can be targeted to develop potential stroke therapies.

PI_NAMEs: O'CINNEIDE, EMMA  (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Adaptive Immune System;adaptive immunity;Affect;Alteplase;Amoxicillin;Animal Model;Anti-Inflammatory Agents;Antibiotic Resistance;Antibiotics;Bacteria;Blood - brain barrier anatomy;Brain;Cause of Death;CD4 Positive T Lymphocytes;Cell Communication;Cell Separation;Cells;Clinical Research;Coculture Techniques;comparison control;Coupled;cytokine;Data;Dendritic Cells;Diet;Diffusion;disability;Disease;Equilibrium;Exhibits;Functional disorder;Gastrointestinal Diseases;Goals;gut microbiota;IL17 gene;Immune;Immunity;immunoregulation;improved;In Vitro;in vitro Model;in vivo;Incubated;Infection;Infiltration;Inflammatory;Innate Immune System;insight;Interleukin-6;Intervention;Intestinal Content;Intestines;Ischemic Brain Injury;ischemic injury;Ischemic Stroke;Ligands;Link;Long term disability;Mediating;Mediator;mesenteric lymph node;microbial composition;microbiota;Middle Cerebral Artery Occlusion;Modeling;Molecular;Mus;Natural Immunity;neuroprotection;NF-kappa B;Outcome;pathogen;Pathology;Pathway interactions;Patients;Pattern recognition receptor;Phenotype;polarized cell;Predisposition;Prevalence;Production;Prognostic Factor;programs;Property;Public Health;Publishing;Receptor Cell;Regulatory T-Lymphocyte;Research;response;response to injury;Role;Sampling;Severities;Shapes;Signal Transduction;simulation;Small Intestines;Stroke;stroke outcome;stroke therapy;Study models;T cell response;T-Lymphocyte;therapeutic target;Tissues;Toll-like receptors;transcription factor;translational study;United States;unpublished works;γδ T cells

PROJECT_TITLE: Intestinal Microbiota Affect Stroke Outcome by Modulating the Dendritic Cell-regulatory T Cell Axis


ORG_CITY: BOSTON

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE Bacterial cell wall synthesis is critical and effective target for antibiotics, yet we lack a fundamental understanding of how new cell wall material is synthesized at the septum between dividing bacteria. We will solve the structure of a novel, division-specific cell wall synthase and reconstitute its activity in vitro. By doing so, we will determine its enzymatic mechanism of action and elucidate how it is regulated by interactions with the cell wall and other division proteins to generate insight for the design of novel antibiotics.

PI_NAMEs: WEAVER, ANNA I (contact)

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Active Sites;Antibiotics;Area;assay development;Bacteria;Bacterial Infections;Binding;Biochemical;Biochemistry;Biological Assay;Boston;career;Cell division;Cell Wall;Cells;Cellular Structures;Cessation of life;Co-Immunoprecipitations;Communities;Complement;Complex;Crystallization;Data;derepression;design;Development;Drug Design;Drug resistance;Drug Targeting;Educational process of instructing;enzyme activity;Enzyme Interaction;Enzymes;experience;experimental study;Family;Fostering;Genetic;glycosyltransferase;Gram-Negative Bacteria;Gram-Positive Bacteria;Grant;higher education;In Vitro;in vitro activity;in vivo;inhibitor;insight;Institution;Investigation;Knowledge;Laboratories;Ligands;Lipid Binding;Mediating;medical schools;member;Membrane;Mentors;Microbiology;Modeling;Modification;mutant;N-Acetylmuramoyl-L-alanine Amidase;novel;novel antibiotic class;pathogen;Peptidoglycan;Peptidoglycan glycosyltransferase;Peptidyltransferase;Physiological;polymerization;Polymers;Postdoctoral Fellow;Preparation;prevent;preventable death;Process;protein complex;Protein Family;Protein Region;Proteins;reconstitution;Regulation;Research Personnel;skills;Streptococcus pneumoniae;Structure;Substrate Interaction;Teichoic Acids;Testing;undergraduate student;Work

PROJECT_TITLE: Biochemical and structural characterization of the cell wall synthesis complex required for bacterial division


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Kidney Disease;Machine Learning and Artificial Intelligence;Neurodegenerative;Neurosciences;Organ Transplantation;Prevention;Transplantation

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Older kidney transplant (KT) recipients are at increased risk of developing dementia/Alzheimer’s disease (AD), which significantly increases the risk of mortality or graft loss. Despite these risks, predicting who will develop post-KT dementia/AD is not part of the pre-KT evaluation. The goal of the proposed project is to identify specific risk factors that are associated with developing post-KT dementia/AD, and to create a model that identifies which patients undergoing KT evaluation are at increased risk of developing post-KT dementia/AD, so that they can receive targeted pre- and post- transplant interventions and additional support.

PI_NAMEs: LONG, JANE J (contact)

PROGRAM_OFFICER_NAME: ROBERTS, LUCI

PROJECT_TERMS: Age;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease risk;Calibration;Cessation of life;Classification;Clinical;Cognitive;cognitive function;cohort;Cohort Studies;Communities;comorbidity;Consensus;Cox Proportional Hazards Models;Data;Dementia;dementia risk;depressive symptoms;design;Development;Diagnosis;Dialysis procedure;Discrimination;Doctor of Philosophy;Elderly;End stage renal failure;Epidemiologic Methods;Ethnic Origin;Evaluation;Event;experience;Faculty;follow-up;frailty;Functional impairment;Funding;Goals;Habilitation;high risk;Hybrids;Impaired cognition;improved;Incidence;Instruction;interest;Intervention;Kidney Diseases;Kidney Transplantation;Learning;Longitudinal cohort study;Machine Learning;Measures;Medical History;medication nonadherence;Mentorship;Methods;mixed dementia;Modeling;mortality risk;neurocognitive test;novel;nutrition;older adult;older patient;Outcome;Outcomes Research;Patients;Pharmaceutical Preparations;post-transplant;post-transplant disease;predictive modeling;predictive tools;prospective;Race;Recording of previous events;recruit;Research;Risk;Risk Factors;risk prediction;Scientist;screening;Self Care;sex;skills;Subgroup;Surgeon;Techniques;Testing;Time;tool;Training;transplant centers;Transplant Recipients;Transplantation;United States National Institutes of Health;Validation;Vascular Dementia

PROJECT_TITLE: Predicting post-kidney transplant dementia/Alzheimer's Disease risk in older patients


NIH_SPENDING_CATS: Genetics;Infectious Diseases;Malaria;Pediatric;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

PHR: PROJECT NARRATIVE Malaria kills hundreds of thousands of children in sub-Saharan Africa each year, but it remains unclear why some infections progress from mild to severe illness. Laboratory studies suggest that diverse parasite antigens called RIFINs and STEVORs may have several roles in severe malaria pathogenesis, but they have not been studied in clinical infections. The goal of this proposal is to identify RIFIN and STEVOR subtypes that are associated with vulnerability to severe malaria in sub-Saharan African children, illuminating the importance of these proteins in pathogenesis and informing the development of vaccines and therapeutics.

PI_NAMEs: LAWTON, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: RAO, MALLA R

PROJECT_TERMS: Acute;Adherence;Africa South of the Sahara;African;Age;Amino Acid Sequence;Antibodies;Antibody Response;Antigens;Binding;Blood;blood group;Blood specimen;Blood typing procedure;career;Cell Surface Proteins;Cells;Cerebral Malaria;Child;Clinical;Clinical Research;Complex;Convalescence;Custom;design;Development;Disease;disease phenotype;Epidemiologist;Erythrocyte Membrane;Erythrocytes;Falciparum Malaria;Family;Gene Expression;Generations;Genetic Polymorphism;Genome;Geographic Locations;Glycophorin C;Goals;Human;Immune;immune clearance;Immunity;Immunologic Epidemiology;In Vitro;Individual;Infection;International;Invaded;Investigation;Laboratory Study;Length;Link;Malaria;malaria infection;malaria transmission;malarial anemia;Malawi;Mali;Measures;Mediating;Mediator;Membrane Proteins;Messenger RNA;Molecular;Morbidity - disease rate;mortality;next generation;novel strategies;Open Reading Frames;Parasites;Pathogenesis;Pattern;Plasmodium falciparum;Predisposition;preference;Preparation;Protein Family;Protein Microchips;Proteins;reference genome;Research;Research Design;response;Risk;Risk Factors;RNA;Role;Sampling;Serology;Serum;Severities;Site;skills;Subgroup;Surface;Surface Antigens;Symptoms;Syndrome;Therapeutic;Time;Training;Transcript;transcriptome sequencing;transcriptomics;Uganda;vaccine development;Vaccines;Variant;Virulence;Vulnerable Populations

PROJECT_TITLE: Deciphering the roles of RIFIN and STEVOR parasite antigens in severe malaria pathogenesis via transcriptomics and immune profiling