Document text
Principal Investigator: Junjie Yao
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $611,361
Funding agency: National Heart Lung and Blood Institute
Abstract
Thrombosis, the obstruction of blood flow due to the formation of clot in blood vessels, accounts for 1 in 4
deaths worldwide. In particular, venous thrombi occur in deep veins most often in the legs or arms and is
commonly known as deep vein thrombosis (DVT). DVT and pulmonary embolism are collectively referred to as
venous thromboembolism (VTE) in which a part of the venous thrombus breaks off, travel to the lungs, and
lodge in pulmonary arteries. VTE is the 3rd leading cause of cardiovascular-related deaths globally with
estimates of >500,000 deaths in the United States every year. VTE is reported to be the leading cause of
disability-adjusted life years lost in hospitalized patients.
Despite the large amount of capital invested in drug development, very few drugs are ultimately proven useful
in humans. Such a low yield occurs largely because planar cell culture and animal models for testing the drugs
oftentimes fail to reflect human physiology/pathology. In contrast, three-dimensional (3D) human cell-based in
vitro models have been increasingly adopted to improve drug testing by recapitulating physiological and
pathological parameters of their human counterparts. In addition to the development of engineered human-
based microtissues, real-time, in situ, non-invasive volumetric monitoring of the behaviors of the engineered
vascular models and their responses towards viral infection/drug treatment is a key capacity to achieve
high(er)-throughput and accurate in vitro screening of promising drug candidates.
Here we propose to harness our unique expertise in engineered in vitro human vascular tissue models and
high-speed label-free imaging of thrombosis with further aid by strong experiences in clinical hematology and
anticoagulation management in patients. Together, we will create an enabling and first-of-its-kind high(er)-
throughput real-time imaging-integrated thrombosis-on-chip model to study thrombosis and potential
therapeutic agents, taking severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as a
timely example to instruct future preparedness for pandemics and other vascular disorders.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><3-D><3-Dimensional><3D><Acute><Adopted><Adventitial Cell><Affect><Alteplase><Angiitis><Animal Model><Animal Models and Related Studies><Anti-viral Agents><Anticoagulation><Antithrombotic Agents><Antithrombotic Drugs><Arteries><Behavior monitoring><Bleeding><Blood Vessels><Blood flow><Body Tissues><COVID assay><COVID-19><COVID-19 assay><COVID-19 infection><COVID-19 virus><COVID-19 virus infection><COVID19 assay><COVID19 infection><COVID19 virus><CV-19><Capital><Cardiovascular><Cardiovascular Body System><Cardiovascular Diseases><Cardiovascular Organ System><Cardiovascular system><Cell Body><Cell Culture Techniques><Cells><Cessation of life><Clinical><Clotting><CoV-2><CoV2><Coagulation><Coagulation Process><Collagen Type I><Coronavirus Infectious Disease 2019><DALY><Death><Deep Vein Thrombosis><Deep-Venous Thrombosis><Development><Disease><Disorder><Dropsy><Drug Screening><Drug Therapy><Drugs><EC 3.4.21.7><Edema><Endothelium><Engineering><European Community><European Union><Event><Extremities><Fiber><Fibrin><Fibrinolyses><Fibrinolysin><Fibrinolysis><Fibrinolytic Agents><Fibrinolytic Drugs><Fibrinolytic Therapy><Fibroblasts><Fibrosis><Functional Imaging><Future><Glu-Plasmin><Goals><Heart Vascular><Hematologist><Hematology><Hemorrhage><Hemostasis><Hemostatic function><High Throughput Assay><Hospital Admission><Hospitalization><Human><Human Engineering><Hydrops><Hypertension><Image><Impairment><In Situ><In Vitro><Infection><Infiltration><Injury><Investigation><Investments><Label><Leg><Leiomyocyte><Libraries><Limb structure><Limbs><Lung><Lung Respiratory System><Medical Directors><Medication><Modeling><Modern Man><Molecular><Morbidity><Morbidity - disease rate><Non-Trunk><Obstruction><Pain><Painful><Pathologic><Pathology><Patients><Penetration><Pericapillary Cell><Pericytes><Perivascular Cell><Pharmaceutical Preparations><Pharmacotherapy><Physician Executives><Physiologic><Physiologic Imaging><Physiological><Physiology><Plasmin><Plasminogen><Post thrombotic syndrome><Post-phlebitic Disease><Postphlebitic Disease><Postphlebitic Syndrome><Postthrombotic syndrome><Process><Profibrinolysin><Proliferating><Protease F><Publications><Pulmonary Artery><Pulmonary Embolism><Pulmonary artery structure><Recombinant Tissue Plasminogen Activator><Reporting><Resolution><Rouget Cells><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 assay><SARS-CoV-2 infection><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Scheme><Scientific Publication><Services><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Site><Smooth Muscle Cells><Smooth Muscle Myocytes><Smooth Muscle Tissue Cell><Speed><System><T-Plasminogen Activator><Therapeutic><Therapeutic Agents><Therapeutic Thrombolysis><Thromboembolism><Thrombolytic Agents><Thrombolytic Drugs><Thrombolytic Therapy><Thrombosis><Thrombus><Time><Tissue Activator D-44><Tissue Model><Tissue Plasminogen Activator><Tissue-Type Plasminogen Activator><Tissues><Travel><Type 1 Collagen><Ulcer><Ulceration><United States><Vascular Diseases><Vascular Disorder><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Vasculitis><Veins><Venous><Venous ulcer-leg syndrome><Viral Diseases><Virus Diseases><Wuhan coronavirus><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-virals><antithrombotic medication><antithrombotics><arm><behavioral monitoring><bio-printing><bioprinting><blood loss><blood vessel disorder><cardiovascular disorder><cell culture><cell cultures><circulatory system><coronavirus disease 2019><coronavirus disease 2019 assay><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease assay><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><cost><deep vein><developmental><disability-adjusted life years><drug candidate><drug detection><drug development><drug testing><drug treatment><drug/agent><experience><hCoV19><high blood pressure><high throughput screening><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><imaging><improved><in vitro Model><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><injuries><injury to the vasculature><life year loss><miniaturize><miniaturized><model of animal><mortality><nCoV2><next generation><optoacoustic imaging><optoacoustic tomography><pandemic disease preparedness><pandemic planning><pandemic preparedness><pandemic readiness><photoacoustic imaging><photoacoustic tomography><physiological imaging><post-phlebitic syndrome><pulmonary><real-time images><realtime image><resolutions><response><screening><screenings><severe acute respiratory syndrome coronavirus 2 assay><small molecule><t-PA><three dimensional><thrombotic><thrombotic disease><thrombotic disorder><vascular><vascular dysfunction><vascular injury><vasculitides><vasculopathy><venous thromboembolism><viral infection><virus infection><virus-induced disease><years of life lost>