James McGrath
William R. Kenan, Jr. Professor of Biomedical Engineering University of Rochester
- Rochester NY
James McGrath and his team focus on the basic science of ultrathin membranes, including studies of transport and mechanics.
Areas of Expertise
Social
Biography
While historically, Professor McGrath's research focused on the phenomena of cell migration, since 2007 he has been leading the Nanomembrane Research Group - a highly interdisciplinary, multi-institutional team that is developing and applying ultrathin silicon ‘nanomembrane' technologies. Professor McGrath is also a co-founder and past president of SiMPore Inc. a company founded to commercially manufacture the nanomembranes. In 2019, he was also a recipient of the Edmund A. Hajim Outstanding Faculty Award, and in 2015 he was elected as a Fellow of the American Institute for Medical and Biological Engineering (AIMBE).
Education
Division of Health Sciences and Technology, Harvard University/MIT
PhD
Biological Engineering
1998
Massachusetts Institute of Technology
MS
Mechanical Engineering
1994
Arizona State University
BS
Mechanical Engineering
1991
Selected Media Appearances
Tissue-on-chip technology holds promise to reduce animal testing
Academic Minute WAMC radio
2025-02-20
On University of Rochester Week: Can computers take over and put an end to animal testing?
James McGrath, William R. Kenan, Jr. professor of biomedical engineering, examines this question
Since 2001, James McGrath has been on the Biomedical Engineering faculty at the University of Rochester and served the department for over 10 years as the first director of the BME graduate program. While historically his research focused on the phenomena of cell migration, since 2007 he has been leading the Nanomembrane Research Group – a highly interdisciplinary, multi-institutional team that is developing and applying ultrathin silicon ‘nanomembrane’ technologies.
Tissue-on-chip technology holds promise to reduce animal testing
In 2022, the FDA Modernization Act 2.0 removed a provision that required animal testing to be used in drug development and opened the door for computer-based models as an alternative. Then the FDA Modernization Act 3.0 was introduced earlier this year, with the goal further reducing animal testing and increasing efficiency of drug trials.
My current research is focused on developing tissue-on-chip or organ-on-a-chip technology, which is one of the promising alternatives to animal testing currently being studied. In simple terms, human cells are arranged in a microfluidic device referred to as a ‘chip.’ The chip mimics healthy or diseased human tissue and provides an accurate representation of how a specific drug or toxin interacts with that tissue.
People are protesting a Wayne County beagle breeder. They want to end animal testing
WXXI radio
2024-08-14
That technology, known as tissue-on-chip or organ-on-a-chip, is one of the more promising alternatives to animal testing currently being studied. That tech, in simplest terms, takes a small sample of human organ cells and places it on a transparent computer chip. The chip is meant to serve as a replica of the organ’s system and give an accurate representation of how a specific drug or toxin interacts with that organ.
James McGrath is a professor of biomedical research at the University of Rochester and one of the scientists leading the development of tissue-on-chip technology. He said the science is promising but is still limited.
“The downside is it models a small part of an organism that’s very complicated and very big, with a lot of interacting systems,” McGrath said. “So that’s what animals provide that these chips, I think, will continue to struggle to provide for a long, long time — is how do these different tissues interact, how does this work at a system level?”
Selected Articles
High levels of endothelial ICAM-1 prohibit abrogation of CD4+ T-cell arrest on the inflamed BBB by extended interval dosing of natalizumab
Journal of NeuroinflammationJames L. McGrath, Sasha Soldati, Alexander Bär, Mykhailo Vladymyrov, Dale Glavin, Fabien Gosselet, Hideaki Nishihara, Susan Goelz, and Britta Engelhardt
2023-05-23
The humanized anti-α4 integrin blocking antibody natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS) that is associated with the risk of progressive multifocal leukoencephalopathy (PML). While extended interval dosing (EID) of NTZ reduces the risk for PML, the minimal dose of NTZ required to maintain its therapeutic efficacy remains unknown.
Modelling a Human Blood-Brain Barrier Co-Culture Using an Ultrathin Silicon Nitride Membrane-Based Microfluidic Device
International Journal of Molecular SciencesJames L. McGrath, Diana Hudecz, Molly C McCloskey, Sandra Vergo, Søren Christensen, and Morten S Nielsen
2023-03-15
Understanding the vesicular trafficking of receptors and receptor ligands in the brain capillary endothelium is essential for the development of the next generations of biologics targeting neurodegenerative diseases. Such complex biological questions are often approached by in vitro models in combination with various techniques. Here, we present the development of a stem cell-based human in vitro blood-brain barrier model composed of induced brain microvascular endothelial cells (iBMECs) on the modular µSiM (a microdevice featuring a silicon nitride membrane) platform.
A computer vision approach for analyzing label free leukocyte trafficking dynamics on a microvascular mimetic
Frontiers in ImmunologyJames L. McGrath, S. Danial Ahmad, Mujdat Cetin, and Richard E. Waugh
2023-03-24
High-content imaging techniques in conjunction with in vitro microphysiological systems (MPS) allow for novel explorations of physiological phenomena with a high degree of translational relevance due to the usage of human cell lines. MPS featuring ultrathin and nanoporous silicon nitride membranes (µSiM) have been utilized in the past to facilitate high magnification phase contrast microscopy recordings of leukocyte trafficking events in a living mimetic of the human vascular microenvironment. Notably, the imaging plane can be set directly at the endothelial interface in a µSiM device, resulting in a high-resolution capture of an endothelial cell (EC) and leukocyte coculture reacting to different stimulatory conditions. The abundance of data generated from recording observations at this interface can be used to elucidate disease mechanisms related to vascular barrier dysfunction, such as sepsis. The appearance of leukocytes in these recordings is dynamic, changing in character, location and time. Consequently, conventional image processing techniques are incapable of extracting the spatiotemporal profiles and bulk statistics of numerous leukocytes responding to a disease state, necessitating labor-intensive manual processing, a significant limitation of this approach. Here we describe a machine learning pipeline that uses a semantic segmentation algorithm and classification script that, in combination, is capable of automated and label-free leukocyte trafficking analysis in a coculture mimetic.
A photonic biosensor-integrated tissue chip platform for real-time sensing of lung epithelial inflammatory markers
Lab on a ChipJames L. McGrath, John S. Cognetti, Maya T. Moen, Matthew G. Brewer, Michael R. Bryan, Joshua D. Tice, and Benjamin L. Miller
2022-12-13
Tissue chip (TC) devices, also known as microphysiological systems (MPS) or organ chips (OCs or OoCs), seek to mimic human physiology on a small scale. They are intended to improve upon animal models in terms of reproducibility and human relevance, at a lower monetary and ethical cost. Virtually all TC systems are analyzed at an endpoint, leading to widespread recognition that new methods are needed to enable sensing of specific biomolecules in real time, as they are being produced by the cells. To address this need, we incorporated photonic biosensors for inflammatory cytokines into a model TC. Human bronchial epithelial cells seeded in a microfluidic device were stimulated with lipopolysaccharide, and the cytokines secreted in response sensed in real time.
A tissue chip with integrated digital immunosensors: In situ brain endothelial barrier cytokine secretion monitoring
Biosensors and BioelectronicsJames L McGrath, Shiuan-Haur Su, Yujing Song, Andrew Stephens, Muyu Situ, Molly C McCloskey, Anuska V Andjelkovic, Benjamin H Singer, and Katsuo Kurabayashi
2022-12-24
Organ-on-a-chip platforms have potential to offer more cost-effective, ethical, and human-resembling models than animal models for disease study and drug discovery. Particularly, the Blood-Brain-Barrier-on-a-chip (BBB-oC) has emerged as a promising tool to investigate several neurological disorders since it promises to provide a model of the multifunctional tissue working as an important node to control pathogen entry, drug delivery and neuroinflammation. A comprehensive understanding of the multiple physiological functions of the tissue model requires biosensors detecting several tissue-secreted substances in a BBB-oC system. However, current sensor-integrated BBB-oC platforms are only available for tissue membrane integrity characterization based on permeability measurement. Protein secretory pathways are closely associated with the tissue's various diseased conditions. At present, no biosensor-integrated BBB-oC platform exists that permits in situ tissue protein secretion analysis over time, which prohibits researchers from fully understanding the time-evolving pathology of a tissue barrier. Herein, the authors present a platform named "Digital Tissue-BArrier-CytoKine-counting-on-a-chip (DigiTACK)," which integrates digital immunosensors into a tissue chip system and demonstrates on-chip multiplexed, ultrasensitive, longitudinal cytokine secretion profiling of cultured brain endothelial barrier tissues.
