Support from the Coronavirus Aid, Relief, and Economic Security (CARES) Act allowed NCATS to quickly distribute additional funding to tissue chip investigators who proposed applying their work to pressing COVID-19 concerns. Investigators suggested projects to evaluate properties of SARS-CoV-2, the virus that causes COVID-19; the mechanisms of COVID-19 disease pathology; potential COVID-19 therapeutics of known action; and the potential repurposing of approved drugs for use against COVID-19. Rapid distribution of funds was essential for the quick initiation of clinically relevant research contributing to the fight against COVID-19.
Click on the links below to learn more about the projects:
- Kidney Microphysiological Analysis Platforms (MAP) to Explore SARS-CoV-2 Receptors and Inhibitors
- A Lung‐Chip Microphysiological System to Model SARS‐CoV‐2 Infection and Test Novel Therapeutics
- Vascular, Cardiac, and Lung Alveolar Human Microphysiological Systems for SARS-COV-2 Drug Screening
- Lung-on-a-Chip Disease Models for Efficacy Testing
- Construction of an Integrated Immune-Vascular Brain-Chip as a Platform for the Study, Drug Screening, and Treatments of Alzheimer’s Disease
- Using the GoFlowChip to Understand SARS-CoV-2 Infection of the Gastrointestinal Mucosa of Humans and Bats
- Organ‐on‐Chip Approach for Assessing Tissue‐Specific SARS‐CoV‐2 Infection and Response to Antiviral Therapy
- A 3-D In Vitro Disease Model of Atrial Conduction
- Microphysiological Systems to Model Vascular Malformations
- Therapeutic Strategies to Test the Mitigation of the Cytokine Storm Syndrome and Coagulopathy in Patient Cell‐Derived vLAMPS with Diabetes and COVID-19 Infection
- Cellular and Molecular Mechanisms of COVID-19 Mediated Kidney Injury
- Drug Development for Tuberous Sclerosis Complex and Other Pediatric Epileptogenic Diseases Using Neurovascular and Cardiac Microphysiological Models
Brigham and Women’s Hospital
Kidney Microphysiological Analysis Platforms (MAP) to Explore SARS‐CoV‐2 Receptors and Inhibitors
Principal Investigator: Joseph Vincent Bonventre, M.D., Ph.D.
Grant Number: 3-UH3-TR-002155-04S1
In some cases of severe COVID-19 infection, patients suffer both kidney and lung damage. This project focuses on the role of Kidney Injury Molecule-1 (KIM-1) as a potential receptor for SARS-CoV-2 in both the kidney and lung. The project will characterize the role of KIM-1 in SARS-CoV-2 binding and cell entry, as well as SARS-CoV-2 inhibitors, using kidney and lung tissue chips. Characterizing SARS-CoV-2 inhibitors will inform the development of therapies to treat COVID-19 and prophylactics to prevent the disease. In addition, KIM-1 will be evaluated for its potential value in diagnostic devices for COVID-19.
Cedars-Sinai Medical Center
A Lung‐Chip Microphysiological System to Model SARS‐CoV‐2 Infection and Test Novel Therapeutics
Principal Investigator: Clive Niels Svendsen, Ph.D.
Grant Number: 3-UG3-NS-105703-03S1
COVID-19 infection can affect lung health and function severely. Preventing COVID-19 viruses from entering the cells and replicating can mitigate or prevent this damage. This project proposes to establish a lung tissue chip with which to investigate SARS-CoV-2 lung infection and test novel antisense oligonucleotide (ASO) therapies that might reduce viral entry and replication. ASOs will be designed to target the virus and the receptors through which the virus enters cells. The lung tissue chip will be infected with SARS-CoV-2, and the designed ASOs will be applied to the infected models to test for treatment efficacy in the form of reductions in viral entry and hindered viral replication within cells. If effective, ASO treatments can directly benefit those suffering from SARS-CoV-2 lung infections.
Vascular, Cardiac, and Lung Alveolar Human Microphysiological Systems for SARS-COV-2 Drug Screening
Principal Investigator: George A. Truskey, Ph.D.
Grant Number: 3-UH3-TR-002142-04S1
This project seeks to use human heart (cardiac), blood vessel (vascular), and lung (lung alveolar) tissue chips to identify compounds that prevent SARS-CoV-2 from entering cells. Compounds of interest will first be tested on normal cells and cells that overexpress the angiotensin-converting enzyme 2 (ACE2) receptor — the receptor through which SARS-CoV-2 can infect cells — to identify those that most effectively prevent cell binding and entry. The heart, vessel, and lung tissue chips will then be used to test compounds of interest identified in the initial screen more robustly by better replicating conditions found in the human body. In doing so, investigators can rapidly identify drug candidates that prevent COVID-19 infection in critical tissues.
Lung-on-a-Chip Disease Models for Efficacy Testing
Principal Investigator: Donald E. Ingber, M.D., Ph.D.
Grant Number: 3-UH3-HL-141797‐04S1
Identifying new treatments for COVID-19 and establishing methods by which to rapidly and effectively test treatment methods for COVID-19 and new viral pandemics is essential. This project will include the development and use of human lung and gastrointestinal tissue chips as in vitro preclinical tools for the rapid discovery of new therapeutics for viral pandemics. The project team’s lung and gastrointestinal tissue chips have been shown to mimic infection by SARS-CoV-2 particles closely, making them suitable models for the screening and identification of new therapeutics to aid COVID-19–infected individuals. Using computational and synthetic chemistry experiments, the investigators will develop new compounds predicted to prevent COVID-19 infection. The newly developed compounds can be tested for activity against COVID-19 using cells, as well as lung and gastrointestinal tissue chips. The team will identify new compounds that prevent coronavirus infection while simultaneously establishing the value of human organ chips as preclinical tools aiding drug discovery.
Massachusetts Institute of Technology
Construction of an Integrated Immune-Vascular Brain-Chip as a Platform for the Study, Drug Screening, and Treatments of Alzheimer’s Disease
Principal Investigator: Li-Huei Tsai, Ph.D.
Grant Number: 3-UG3-NS-115064-01S1
COVID-19 infection has been shown to affect people in many different ways, which can include the presentation of neurological effects and damage to brain tissue or function. Studying the brain, however, can be difficult due to its complicated cellular and genetic variability. This project proposes to develop a brain tissue chip that incorporates different neurological cell types to simulate the full organ, which can then be used to determine whether specific cell types in the brain are more or less susceptible to COVID-19 infection and adverse reactions. In addition, the project investigators will be evaluating different cell types representing genetic diversity to provide insight into the molecular mechanisms explaining why the neurological impact of COVID-19 differs so much among patients. This knowledge would inform the search for U.S. Food and Drug Administration-approved drugs that are capable of reducing viral infectivity, thereby leading to the establishment of prevention or treatment methods that will protect the brains of patients with COVID-19.
Montana State University, Bozeman
Using the GoFlowChip to Understand SARS-CoV-2 Infection of the Gastrointestinal Mucosa of Humans and Bats
Principal Investigator: Seth T. Walk, Ph.D.
Grant Number: 3-U01-EB-029242‐02S1
COVID-19 infection in the gastrointestinal (GI) tract could occur orally and then spread throughout the body, or it could occur as a secondary site of infection following spread from an initial respiratory infection. To differentiate between these infection possibilities, investigators of this project propose to infect different components of gut tissue chips that represent different cell types in the GI tract. The infectivity of one cell subset would indicate oral GI infection, whereas infectivity of the other cell subset would indicate secondary GI infection following primary respiratory infection. Investigators will evaluate affected cells for SARS-CoV-2–mediated cell death and permeability changes in cell barriers. The investigators also will study the role of specific immune cells in SARS-CoV-2 infection and transmission, and they will study whether the blood plasma from recovered COVID-19 patients can prevent SARS-CoV 2 infection in new cells. Finally, the investigators will use human and bat gut tissue chips to determine why COVID-19 is highly dangerous to humans but not bats.
Organ‐on‐Chip Approach for Assessing Tissue‐Specific SARS‐CoV‐2 Infection and Response to Antiviral Therapy
Principal Investigator: Thomas Neumann, M.D.
Grant Number: 3-R44-TR-003065-02S1
Many potential medical treatments that look promising during early testing fail during clinical testing because they cause unforeseen damage to the kidneys. Because animal kidneys differ significantly from human kidneys and 2-D models using human kidney cells are not structured in a way that adequately represents 3-D kidney cell function, testing compounds for toxicity to the kidneys before they enter clinical trials has been challenging. In this project, investigators will use a kidney tissue chip that better models human kidney function, along with vascular and lung tissue chips, to test the effects of five clinically important COVID-19 treatments. The tissue chips also will be infected with three different COVID-19 strains: the Wuhan strain; the UK variant strain, spike mutation D614G; and a pseudovirus. Performing these tests will validate the utility of these new tissue chip models while enabling the assessment of antiviral effects against COVID-19 strains in these critical tissues.
University of California, Davis
A 3-D In Vitro Disease Model of Atrial Conduction
Principal Investigator: Steven Carl George, M.D., Ph.D.
Grant Number: 3-UH3-HL-141800-04S1
In some cases of COVID-19 infection, the heart acquires both acute and long-term damage, with some patients experiencing lasting heart damage months after they have recovered from their initial infection. Investigators for this project will use a heart tissue chip model to assess the potential benefit of two new therapies in mitigating heart damage caused by COVID-19 infection. One therapy is intended to prevent a COVID-19–induced inflammatory response (i.e., the cytokine storm) that can lead to blood clots, sudden cardiac failure, or degenerative cardiac disease. The second therapy is intended to prevent increased cardiac morbidity (disease) and mortality (death) brought on by COVID-19 viral infection of the heart. With a realistic and complex heart tissue chip incorporating several different cell sets affected by different COVID-19–initiated injuries, these therapies can be evaluated safely and effectively for their ability to protect the heart.
University of California, Irvine
Microphysiological Systems to Model Vascular Malformations
Principal Investigator: Christopher C. W. Hughes, Ph.D.
Grant Number: 3-UH3-HL-141799-04S1
COVID-19 infection can affect multiple organs. It remains unknown, however, whether these multi-organ effects are brought on by secondary infections that spread from primary infection sites or a broad inflammatory effect that targets the vasculature of multiple organs. The investigators driving this project have generated vascularized micro-organ tissue chips with which they can assess whether a broad inflammatory reaction is responsible for the involvement of multiple organs in COVID-19 infections. Using these vascularized organ tissue chips, the project team will test potential treatments preventing SARS-CoV-2 entry into cells, and they will evaluate the potential cause of hyperinflammation-driven tissue damage in the vasculature of multiple organs. By using their vascularized micro-organ tissue chips, this team can elucidate the cause of organ damage in COVID-19 infections and evaluate the means of mitigating that damage.
University of Pittsburgh
Therapeutic Strategies to Test the Mitigation of the Cytokine Storm Syndrome and Coagulopathy in Patient Cell‐Derived vLAMPS with Diabetes and COVID-19 Infection
Principal Investigator: Lansing D. Taylor, Ph.D.
Grant Number: 3-UH3-DK-119973-03S1
Tens of millions of adults in the United States had been diagnosed as having diabetes when COVID-19 arrived in the country. Quickly thereafter, diabetes became one of the preexisting conditions correlated with severe outcomes from COVID-19 infection and was categorized as a risk factor. This project will use liver tissue chips to study the effects of diabetes in the context of COVID-19 infection, specifically testing the hypothesis that COVID-19 infection and diabetes exacerbate each other with a feed-forward loop by which COVID-19 infection increases glucose production and insulin resistance in patients who are diabetic. Investigators will expose the liver tissue chip to a diabetic environment while infecting the cells with SARS-CoV-2 to model this phenomenon. The team will use this model to test potential therapies that can prevent this devastating feed-forward loop and prevent diabetic symptoms. This project has the potential to greatly aid a growing population of people with diabetes that is particularly vulnerable to the threat of the COVID-19 pandemic.
University of Washington
Cellular and Molecular Mechanisms of COVID-19 Mediated Kidney Injury
Principal Investigator: Jonathan Himmelfarb, M.D.
Grant Number: 3-UH3-TR-002158-04S1
Between 30% and 40% of patients with severe COVID-19 infection develop acute kidney injury, with many of these patients requiring dialysis therapy in the intensive care unit. Currently, no treatment exists to target COVID-19–induced kidney injury. Determining the molecular processes associated with COVID-19 in patients with kidney disease, however, could lead to the development of treatments for these patients and greatly improve public health outcomes in this population. This project team has developed kidney tissue chips that recapitulate kidney physiology, facilitate researchers’ investigation of injury response mechanisms in the kidneys, and enable the evaluation of repair mechanisms in the kidney. Using these kidney tissue chips, project investigators will characterize the expression, binding, engagement, and modulation of receptors that SARS-CoV-2 uses to infect cells. They also will use these kidney tissue chips to assess potential COVID-19 therapeutics’ ability to prevent SARS-CoV-2 infection and injury in kidney cells.
Drug Development for Tuberous Sclerosis Complex and Other Pediatric Epileptogenic Diseases Using Neurovascular and Cardiac Microphysiological Models
Principal Investigator: John Peter Wikswo, Ph.D.
Grant Number: 3-UH3-TR-002097-04S1
COVID-19 is widely recognized as a respiratory disease, but COVID-19 infection also can affect multiple systems in the body, including the central nervous system (CNS). This project aims to discover the connection between the lungs and the CNS in COVID-19 infection and model how the viral infection progresses in these organ systems. Using lung and brain tissue chips, the team will infect model cell systems with live SARS-CoV-2 and test the antiviral and anti-inflammatory effectiveness of six potential therapeutic compounds. The investigators will determine how COVID-19 infection moves from the primary site of infection in the lungs into the CNS, which will allow them to determine which therapies serve to prevent that transition and lead to immediate clinical benefit for patients.