2017/2018 Tissue Chips for Disease Modeling and Efficacy Testing Projects

In September 2017, NIH funded 13 institutions with initial two-year awards to further develop tissue chip models of human disease that mimic the pathology in major human organs and tissues. In February 2018, NCATS issued an additional award. The goals are to (1) support studies to develop in vitro disease models using primary tissue or induced pluripotent stem cell (iPSC)-derived patient cell sources on tissue/organ-on-chip platforms, (2) determine disease relevance of these models by preliminary testing of key experimental features, and (3) test the effectiveness of candidate drugs.

Access the links below to learn more about the 2017/2018 awarded projects:

Brigham and Women’s Hospital

Kidney Microphysiological Analysis Platforms to Optimize Function and Model Disease*

Principal Investigators: Joseph Vincent Bonventre, M.D., Ph.D. (Brigham and Women’s Hospital) and Luke P. Lee, Ph.D. (University of California, Berkeley)
Grant Number: 1-UG3-TR-002155-01

The proposed work will take advantage of new technologies in stem cell biology, genome editing, microfabrication, microfluidics and bioprinting to model kidney diseases, and it will establish systems to test for drug development, to test for efficacy and screen for kidney toxicity using human tissue. 

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Cedars-Sinai Medical Center

Development of a Microphysiological Organ-on-Chip System to Model Amyotrophic Lateral Sclerosis and Parkinson’s Disease*

Principal Investigator: Clive Niels Svendsen, Ph.D.
Grant Number: 1-UG3-NS-105703-01

In a collaboration between the microphysiological systems company Emulate Inc. and Cedars-Sinai Medical Center, this project will establish novel biomarkers for sporadic forms of amyotrophic lateral sclerosis and Parkinson’s disease. Project staff will then perform a screen of compounds that can reverse patient-specific biomarkers, using the NCATS small molecule library. 

Learn more about this project in NIH RePORTER.

*Funded by the National Institute of Neurological Disorders and Stroke (NINDS) with additional funding from NCATS.

Columbia University Health Sciences

Integrated Microphysiological System of Cerebral Organoid and Blood Vessel for Disease Modeling and Neuropsychiatric Drug Screening

Principal Investigator: Kam W. Leong, Ph.D.
Grant Number: 1-UG3-TR-002151-01

Neuropsychiatric disorders, such as autism, epilepsy and schizophrenia, are increasing in the U.S. population. However, treatments for these disorders have lagged because so many drugs fail in development. Recent advances in stem cell technology have made it possible to create patient-specific brain-like tissue from stem cells that functions like human brain tissue. This research team seeks to link this brain-like tissue with an engineered blood vessel and blood-brain barrier to form a cerebral microphysiological system. This system will help the team better understand the interactions between the central nervous system and its blood vessels, and it could be used to learn more about neuropsychiatric disorders as well as to develop and test new medicines.

Learn more about this project in NIH RePORTER.

*Funded by NCATS.

Columbia University in the City of New York, Morningside Heights

Multi-Tissue Platform for Modeling Systemic Pathologies*

Principal Investigator: Gordana Vunjak-Novakovic, M.S., Ph.D.
Grant Number: 1-UG3-EB-025765-01

Project staff will establish a testing platform with five functionally connected tissue units: heart, liver, skin, bone and vasculature ― all grown from the patient’s cells ― and perfused with a blood substitute containing immune cells. To validate the platform, project staff will model the toxic effects of doxorubicin, a drug used to treat many human cancers. The goal is to show that the proposed multi-tissue platform can replicate the transcriptional, metabolic and functional changes observed in patients and be used to develop better therapeutic regimens.

Learn more about this project in NIH RePORTER.

*Funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) with additional funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Environmental Health Sciences (NIEHS), National Institute of Dental and Craniofacial Research (NIDCR), and NCATS.

Duke University

Systemic Inflammation in Microphysiological Models of Muscle and Vascular Disease*

Principal Investigator: George A. Truskey, Ph.D.
Grant Number: 1-UG3-TR-002142-01

This project involves creating laboratory-based disease models in blood vessels and skeletal muscle, using human cells. The models will replicate key features of inflammation. Once validated, the laboratory models will be used to test new drugs and assess the variation in the response to the drug among the population.

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from NIAMS.

Harvard University

Lung-on-a-Chip Disease Models for Efficacy Testing*

Principal Investigator: Donald E. Ingber, M.A., M.D., Ph.D.
Grant Number: 1-UG3-HL-141797-01 

The goal of this project is to create in vitro models of influenza virus infection by using microfluidic human organ-on-a-chip culture devices that recapitulate clinical features of the disease and demonstrate that they can be used for drug screening and discovery of new antiviral therapeutics. This novel influenza disease model will then be linked to human liver chips that carry out drug metabolism to conduct preclinical efficacy and safety testing of existing antiviral drugs, identify new potential drug targets, and discover new therapeutics that target the host response to infection, rather than the virus itself.

Learn more about this project in NIH RePORTER.

*Funded by the National Heart, Lung, and Blood Institute (NHLBI) with additional funding from NCATS and NIEHS.

Harvard University

Multi-Scale Modeling of Inherited Pediatric Cardiomyopathies*

Principal Investigators: Kevin Kit Parker, M.S., Ph.D., and William Tswenching Pu, M.S., M.D.
Grant Number: 1-UG3-HL-141798-01   

Project staff will use healthy and diseased heart cells derived from patients to build laboratory models of heart muscle. Cell pairs, 2-D sheets, and 3-D model ventricle chambers will be tested to understand disease mechanisms and to screen small molecules and gene therapies for improved outcomes. Project staff envision the eventual use of these platforms for “clinical trials in a dish."

Learn more about this project in NIH RePORTER.

*Funded by NHLBI with additional funding from NCATS.

Northwestern University

Polycystic Ovary Syndrome (PCOS) and Androgen-Related Disease Modeling and Drug Testing in Multi-Organ Integrated Microfluidic Reproductive Platform*

Principal Investigator: Teresa K. Woodruff, Ph.D.
Grant Number: 1-UG3-ES-029073-01

PCOS is a highly prevalent human health crisis for women in their reproductive years, but there are no good animal models of the disease. This project team has created a next-generation technology that can be used in the general- or high-throughput tissue culture lab and will support human and mouse tissues (ovaries, fallopian tubes, uterus, cervix, adipose, liver and pancreas) under the influence of androgen. Project staff will use this model to test drugs that target androgen production as well as existing insulin-sensitizing drugs and a new class of drugs that is under development for PCOS by the team’s pharmaceutical partner, AstraZeneca.

Learn more about this project in NIH RePORTER.

*Funded by NIEHS with additional funding from the NIH Office of the Director and NCATS.

University of California, Davis

A 3-D In Vitro Disease Model of Atrial Conduction*

Principal Investigators: David Terry Curiel, M.D., Ph.D. (Washington University in St. Louis); Steven Carl George, M.D., Ph.D. (University of California, Davis); and Stacey Lynn Rentschler, M.D., Ph.D. (Washington University in St. Louis)
Grant Number: 1-UG3-HL-141800-01

The central objective of this proposal is to create and validate a robust 3-D in vitro microphysiological model of human atrial conduction, using patient-derived induced pluripotent stem cells. The model can be used to test the safety and efficacy of drugs to treat atrial arrhythmias, such as atrial fibrillation, in a precision medicine format.

Learn more about this project in NIH RePORTER.

*Funded by NHLBI with additional funding from NCATS.

University of California, Irvine

Microphysiological Systems to Model Vascular Malformations*

Principal Investigator: Christopher C.W. Hughes, Ph.D.
Grant Number: 1-UG3-HL-141799-01

This proposal will seek to develop novel microfluidic “VM-on-a-chip” platforms for studying various vascular malformations, including hereditary hemorrhagic telangiectasia and port-wine stain. This platform will provide a new tool to help researchers understand, treat and ultimately prevent these often disfiguring — and, all too frequently, fatal — anomalies.

Learn more about this project in NIH RePORTER.

*Funded by NHLBI with additional funding from NCATS.

University of Pittsburgh

Tissue Chip Modeling of Synovial Joint Pathologies: Effects of Inflammation and Adipose-Mediated Diabetic Complications*

Principal Investigator: Rocky S. Tuan, Ph.D.
Grant Number: 1-UG3-TR-002136-01

Project staff propose to develop a human micro-joint chip (mJoint) from human primary cells or stem cells that contains interconnected engineered principal tissue elements of the joint (osteochondral complex, synovium, and adipose tissues) to simulate the synovial joint in vivo. The mJoint will be set up to model osteoarthritis, septic arthritis and inflamed arthritis, and adipose-mediated diabetic joint complications.

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from NIAMS.

University of Rochester

Engineered Salivary Gland Tissue Chips*

Principal Investigators: Danielle S. Benoit, M.S., Ph.D., Lisa A. Delouise, Ph.D., and Catherine Ovitt, Ph.D.
Grant Number: 1-UG3-DE-027695-01

More than 550,000 patients worldwide are diagnosed with head and neck cancers annually, and many will develop permanent xerostomia, or dry mouth, due to salivary gland damage from radiation therapy. This proposal will develop a 3-D engineered, high-throughput culture platform to promote the development of functional human salivary gland mimetics. The platform utility will be demonstrated by high-throughput screening for new radioprotective compounds, which will be validated in murine radiation damage models.

Learn more about this project in NIH RePORTER.

*Funded by NIDCR with additional funding from NCATS.

University of Washington

A Microphysiological System for Kidney Disease Modeling and Drug Efficacy Testing*

Principal Investigator: Jonathan Himmelfarb, M.D.
Grant Number: 1-UG3-TR-002158-01

Chronic kidney disease is a public health problem affecting more than 20 million U.S. adults and is the ninth leading cause of death in the United States. The goal of this project is to model important human kidney diseases and promote identification of safe and effective treatments. If successful, in vitro models that recapitulate critical aspects of kidney physiological function, response to injury, and repair could contribute greatly to drug discovery and development. Ultimately, it could also enable “virtual clinical trials” for candidate therapeutics.

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from NIDDK.

Vanderbilt University

Drug Development for Tuberous Sclerosis Complex and Other Pediatric Epileptogenic Diseases Using Neurovascular and Cardiac Microphysiological Models*

Principal Investigators: Aaron B. Bowman, Ph.D., Kevin C. Ess, M.D., Ph.D., and John Peter Wikswo, M.S., Ph.D.
Grant Number: 1-UG3-TR-002097-01

This research will develop in vitro tissue chip models of the neurological disorder tuberous sclerosis complex and other pediatric epileptogenic diseases. This technological platform, which makes use of human-induced pluripotent stem cells derived from patients suffering from these disorders, will create neural and cardiac tissue models that will more faithfully replicate actual human disease and drug response than those currently in use. This platform will be a demonstration of patient-specific studies for “precision medicine” and will ultimately enable the development of effective therapies.

Learn more about this project in NIH RePORTER.

*Funded by NCATS with additional funding from NINDS.

Contact

Danilo Tagle, Ph.D.

2017 Disease Modeling Awards

lung-on-chipIn September 2017, NCATS announced 13 awards to develop 3-D tissue chip research platforms that model disease and test drug efficacy prior to clinical trials. View the projects.