“Lorna's expertise has been incredibly valuable in enhancing our knowledge in the field of organ-on-a-chip technologies. Her in-depth scientific understanding coupled with awareness and insight on real-life applications, pragmatic analysis of barriers to progress and how these may be overcome, has equipped us to understand the potential of these state-of-the-art in vitro models for our business. Lorna has helped us to evaluate how the systems could play a part in our mission to accelerate the world's transition to 100% animal-free testing. Along the way she has acted at all times with an extremely high degree of integrity, transparency and commitment to deliver the objectives of the project. I'm very glad to have met Lorna and she's a shining star in my professional network!”
About
At Emulate, Inc., our team is pioneering the commercialization of innovative in vitro…
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𝐃𝐚𝐲 𝟏 𝐚𝐭 𝐭𝐡𝐞 𝐃𝐌𝐃𝐆 𝟓𝟎𝐭𝐡 𝐎𝐩𝐞𝐧 𝐌𝐞𝐞𝐭𝐢𝐧𝐠 𝐚𝐭 𝐭𝐡𝐞 𝐔𝐧𝐢𝐯𝐞𝐫𝐬𝐢𝐭𝐲 𝐨𝐟 𝐘𝐨𝐫𝐤! Our talented team members, Barry…
𝐃𝐚𝐲 𝟏 𝐚𝐭 𝐭𝐡𝐞 𝐃𝐌𝐃𝐆 𝟓𝟎𝐭𝐡 𝐎𝐩𝐞𝐧 𝐌𝐞𝐞𝐭𝐢𝐧𝐠 𝐚𝐭 𝐭𝐡𝐞 𝐔𝐧𝐢𝐯𝐞𝐫𝐬𝐢𝐭𝐲 𝐨𝐟 𝐘𝐨𝐫𝐤! Our talented team members, Barry…
Liked by Lorna Ewart
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Were we fully aware of what we were stepping into when embarking on this project? Definitely not! But we are very proud of the end result: the…
Were we fully aware of what we were stepping into when embarking on this project? Definitely not! But we are very proud of the end result: the…
Liked by Lorna Ewart
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Despite remarkable advances in Organ Chip technology, it's been tough to recreate real-life conditions like region-specific oxygen…
Despite remarkable advances in Organ Chip technology, it's been tough to recreate real-life conditions like region-specific oxygen…
Liked by Lorna Ewart
Experience
Education
Publications
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Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology
Nature Communications Medicine
Drug development is lengthy and costly, as it relies on laboratory models that fail to predict human reactions to potential drugs. Because of this, toxic drugs sometimes go on to harm humans when they reach clinical trials or once they are in the marketplace. Organ-on-a-Chip technology involves growing cells on small devices to mimic organs of the body, such as the liver. Organ-Chips could potentially help identify toxicities earlier, but there is limited research into how well they predict…
Drug development is lengthy and costly, as it relies on laboratory models that fail to predict human reactions to potential drugs. Because of this, toxic drugs sometimes go on to harm humans when they reach clinical trials or once they are in the marketplace. Organ-on-a-Chip technology involves growing cells on small devices to mimic organs of the body, such as the liver. Organ-Chips could potentially help identify toxicities earlier, but there is limited research into how well they predict these effects compared to conventional models. In this study, we analyzed 870 Liver-Chips to determine how well they predict drug-induced liver injury, a common cause of drug failure, and found that Liver-Chips outperformed conventional models. These results suggest that widespread acceptance of Organ-Chips could decrease drug attrition, help minimize harm to patients, and generate billions in revenue for the pharmaceutical industry.
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Opportunities and challenges with microphysiological systems: a pharma end-user perspective
Nature Reviews Drug Discovery
Using human-relevant, translational in vitro models is widely considered to reduce attri-tion during drug discovery and development. Despite this, the adoption of models based on microphysiological systems — organs-on-chips or organoids — by pharma companies is moderate at best, and realizing the full potential of these models will need greater collaboration between stakeholders.
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On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology
Nature Biomedical Engineering
The inaccessibility of living bone marrow (BM) hampers the study of its pathophysiology under myelotoxic stress induced by drugs, radiation or genetic mutations. Here, we show that a vascularized human BM-on-a-chip (BM chip) supports the differentiation and maturation of multiple blood cell lineages over 4 weeks while improving CD34 cell maintenance, and that it recapitulates aspects of BM injury, including myeloerythroid toxicity after clinically relevant exposures to chemotherapeutic drugs…
The inaccessibility of living bone marrow (BM) hampers the study of its pathophysiology under myelotoxic stress induced by drugs, radiation or genetic mutations. Here, we show that a vascularized human BM-on-a-chip (BM chip) supports the differentiation and maturation of multiple blood cell lineages over 4 weeks while improving CD34 cell maintenance, and that it recapitulates aspects of BM injury, including myeloerythroid toxicity after clinically relevant exposures to chemotherapeutic drugs and ionizing radiation, as well as BM recovery after drug-induced myelosuppression. The chip comprises a fluidic channel filled with a fibrin gel in which CD34 cells and BM-derived stromal cells are co-cultured, a parallel channel lined by human
vascular endothelium and perfused with culture medium, and a porous membrane separating the two channels. We also show that BM chips containing cells from patients with the rare genetic disorder Shwachman–Diamond syndrome reproduced key haematopoietic defects and led to the discovery of a neutrophil maturation abnormality. As an in vitro model of haematopoietic dysfunction, the BM chip may serve as a human-specific alternative to animal testing for the study of BM pathophysiology. -
Reproducing human and cross-species drug toxicities using a Liver-Chip
Science Translational Medicine
Candidate drug testing using standard preclinical models cannot accurately predict which compounds are likely to cause drug-induced liver injury in humans. To improve selection of promising drug candidates, Jang et al. developed a Liver-Chip consisting of rat, dog, or human hepatocytes, endothelial cells, Kupffer cells, and stellate cells. Using the microfluidic chips, the authors confirmed mechanism of action of several known hepatotoxic drugs and an experimental compound. A second…
Candidate drug testing using standard preclinical models cannot accurately predict which compounds are likely to cause drug-induced liver injury in humans. To improve selection of promising drug candidates, Jang et al. developed a Liver-Chip consisting of rat, dog, or human hepatocytes, endothelial cells, Kupffer cells, and stellate cells. Using the microfluidic chips, the authors confirmed mechanism of action of several known hepatotoxic drugs and an experimental compound. A second experimental compound that induced fibrosis in a rat Liver-Chip did not alter hepatocyte function in human chips, whereas a third compound demonstrated increased toxicity in a dog Liver-Chip. Results support using multispecies chips to identify species-specific differences in drug metabolism and toxicity.
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On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships
Nature Scientific Reports
Functional human-on-a-chip systems hold great promise to enable quantitative translation to in vivo outcomes. Here, we explored this concept using a pumpless heart only and heart:liver system to evaluate the temporal pharmacokinetic/pharmacodynamic (PKPD) relationship for terfenadine. There was a time dependent drug-induced increase in field potential duration in the cardiac compartment in response to terfenadine and that response was modulated using a metabolically competent liver module that…
Functional human-on-a-chip systems hold great promise to enable quantitative translation to in vivo outcomes. Here, we explored this concept using a pumpless heart only and heart:liver system to evaluate the temporal pharmacokinetic/pharmacodynamic (PKPD) relationship for terfenadine. There was a time dependent drug-induced increase in field potential duration in the cardiac compartment in response to terfenadine and that response was modulated using a metabolically competent liver module that converted terfenadine to fexofenadine. Using this data, a mathematical model was developed to predict the effect of terfenadine in preclinical species. Developing confidence that microphysiological models could have a transformative effect on drug discovery, we also tested a previously discovered proprietary AstraZeneca small molecule and correctly determined the cardiotoxic response to its metabolite in the heart:liver system. Overall our findings serve as a guiding principle to future investigations of temporal concentration response relationships in these innovative in vitro models, especially, if validated across multiple time frames, with additional pharmacological mechanisms and molecules representing a broad chemical diversity.
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Integrated in vitro models for hepatic safety and metabolism: evaluation of a human Liver-Chip and liver spheroid
Archives of Toxicology
Drug-induced liver injury remains a frequent reason for drug withdrawal. Accordingly, more predictive and translational models are required to assess human hepatotoxicity risk. This study presents a comprehensive evaluation of two promising models to assess mechanistic hepatotoxicity, microengineered Organ-Chips and 3D hepatic spheroids, which have enhanced liver phenotype, metabolic activity and stability in culture not attainable with conventional 2D models. Sensitivity of the models to two…
Drug-induced liver injury remains a frequent reason for drug withdrawal. Accordingly, more predictive and translational models are required to assess human hepatotoxicity risk. This study presents a comprehensive evaluation of two promising models to assess mechanistic hepatotoxicity, microengineered Organ-Chips and 3D hepatic spheroids, which have enhanced liver phenotype, metabolic activity and stability in culture not attainable with conventional 2D models. Sensitivity of the models to two hepatotoxins, acetaminophen (APAP) and fialuridine (FIAU), was assessed across a range of cytotoxicity biomarkers (ATP, albumin, miR-122, α-GST) as well as their metabolic functionality by quantifying APAP, FIAU and CYP probe substrate metabolites. APAP and FIAU produced dose- and time-dependent increases in miR-122 and α-GST release as well as decreases in albumin secretion in both Liver-Chips and hepatic spheroids. Metabolic turnover of CYP probe substrates, APAP and FIAU, was maintained over the 10-day exposure period at concentrations where no cytotoxicity was detected and APAP turnover decreased at concentrations where cytotoxicity was detected. With APAP, the most sensitive biomarkers were albumin in the Liver-Chips (EC50 5.6 mM, day 1) and miR-122 and ATP in the liver spheroids (14-fold and EC50 2.9 mM, respectively, day 3). With FIAU, the most sensitive biomarkers were albumin in the Liver-Chip (EC50 126 µM) and miR-122 (15-fold) in the liver spheroids, both on day 7. In conclusion, both models exhibited integrated toxicity and metabolism, and broadly similar sensitivity to the hepatotoxicants at relevant clinical concentrations, demonstrating the utility of these models for improved hepatotoxicity risk assessment.
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Introducing an automated high content confocal imaging approach for Organs-on-Chips
Lab-on-a-chip
Organ-Chips are micro-engineered systems that aim to recapitulate the organ microenvironment. Implementation of Organ-Chips within the pharmaceutical industry aims to improve the probability of success of drugs reaching late stage clinical trial by generating models for drug discovery that are of human origin and have disease relevance. We are adopting the use of Organ-Chips for enhancing pre-clinical efficacy and toxicity evaluation and prediction. Whilst capturing cellular phenotype via…
Organ-Chips are micro-engineered systems that aim to recapitulate the organ microenvironment. Implementation of Organ-Chips within the pharmaceutical industry aims to improve the probability of success of drugs reaching late stage clinical trial by generating models for drug discovery that are of human origin and have disease relevance. We are adopting the use of Organ-Chips for enhancing pre-clinical efficacy and toxicity evaluation and prediction. Whilst capturing cellular phenotype via imaging in response to drug exposure is a useful readout in these models, application has been limited due to difficulties in imaging the chips at scale. Here we created an end-to-end, automated workflow to capture and analyse confocal images of multicellular Organ-Chips to assess detailed cellular phenotype across large batches of chips. By automating this process, we not only reduced acquisition time, but we also minimised process variability and user bias. This enabled us to establish, for the first time, a framework of statistical best practice for Organ-Chip imaging, creating the capability of using Organ-Chips and imaging for routine testing in drug discovery applications that rely on quantitative image data for decision making. We tested our approach using benzbromarone, whose mechanism of toxicity has been linked to mitochondrial damage with subsequent induction of apoptosis and necrosis, and staurosporine, a tool inducer of apoptosis. We also applied this workflow to assess the hepatotoxic effect of an active AstraZeneca drug candidate illustrating its applicability in drug safety assessment beyond testing tool compounds. Finally, we have demonstrated that this approach could be adapted to Organ-Chips of different shapes and sizes through application to a Kidney-Chip.
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Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model
Nature Scientific Reviews
Human in vitro physiological models studying disease and drug treatment effects are urgently needed as more relevant tools to identify new drug targets and therapies. We have developed a human microfluidic two-organ-chip model to study pancreatic islet–liver cross-talk based on insulin and glucose regulation. We have established a robust co-culture of human pancreatic islet microtissues and liver spheroids maintaining functional responses up to 15 days in an insulin-free medium. Functional…
Human in vitro physiological models studying disease and drug treatment effects are urgently needed as more relevant tools to identify new drug targets and therapies. We have developed a human microfluidic two-organ-chip model to study pancreatic islet–liver cross-talk based on insulin and glucose regulation. We have established a robust co-culture of human pancreatic islet microtissues and liver spheroids maintaining functional responses up to 15 days in an insulin-free medium. Functional coupling, demonstrated by insulin released from the islet microtissues in response to a glucose load applied in glucose tolerance tests on different days, promoted glucose uptake by the liver spheroids. Co-cultures maintained postprandial glucose concentrations in the circulation whereas glucose levels remained elevated in both single cultures. Thus, insulin secreted into the circulation stimulated glucose uptake by the liver spheroids, while the latter, in the absence of insulin, did not consume glucose as efficiently. As the glucose concentration fell, insulin secretion subsided, demonstrating a functional feedback loop between the liver and the insulin-secreting islet microtissues. Finally, inter-laboratory validation verified robustness and reproducibility. Further development of this model using tools inducing impaired glucose regulation should provide a unique in vitro system emulating human type 2 diabetes mellitus.
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Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery
Annual Reviews Pharmacology and Toxicology
Enhancing the early detection of new therapies that are likely to carry a safety liability in the context of the intended patient population would provide a major advance in drug discovery. Microphysiological systems (MPS) technology offers an opportunity to support enhanced preclinical to clinical translation through the generation of higher-quality preclinical physiological data. In this review, we highlight this technological opportunity by focusing on key target organs associated with drug…
Enhancing the early detection of new therapies that are likely to carry a safety liability in the context of the intended patient population would provide a major advance in drug discovery. Microphysiological systems (MPS) technology offers an opportunity to support enhanced preclinical to clinical translation through the generation of higher-quality preclinical physiological data. In this review, we highlight this technological opportunity by focusing on key target organs associated with drug safety and metabolism. By focusing on MPS models that have been developed for these organs, alongside other relevant in vitro models, we review the current state of the art and the challenges that still need to be overcome to ensure application of this technology in enhancing drug discovery.
Honors & Awards
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Lush Prize for Science
Lush Prize
The science prize is awarded to individuals, research teams or institutions for work most likely to lead to practical non-animal tests which could be accepted by regulators. Emulate were awarded £50,000 for the Liver-Chip model which showed superior predictive capability compared to animal models for predicting drug-induced liver injury (DILI).
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Best Paper 2023
Society of Toxicology(SOT) In Vitro and Alternative Methods (IVAM) Speciality Section
Publication: Optimal experimental design for efficient toxicity testing in microphysiological systems: A bone marrow application.
Front. Pharmacol., 31 March 2023
Sec. Predictive Toxicology
Volume 14 - 2023 | https://doi.org/10.3389/fphar.2023.1142581 -
Honorary Degree Doctor of Science (DSc)
Queen Mary, University of London
Awarded in recognition of Lorna’s career in pharmacology, and ground-breaking contributions towards improving drug discovery through advancement of organ-on-a-chip technology.
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Fellow of British Pharmacological Society
British Pharmacological Society
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Chartered biologist
Royal Society of Biology
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UK/EU registered toxicologist
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Fellow of the Royal Society of Biology
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“In a study published in 2022 in Communications Medicine, an Emulate-led team evaluated 870 liver chips across a blinded set of 27 known hepatotoxic…
“In a study published in 2022 in Communications Medicine, an Emulate-led team evaluated 870 liver chips across a blinded set of 27 known hepatotoxic…
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A topic close to my heart, written with my friends and collaborators from social sciences.
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Do you want to learn more about Innovations in predictive toxicology? Read all articles FREE online for one month only (until 31st September…
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Do you remember what you were doing in January? 🤔 At Emulate, Inc. we embarked on the #MyGreenLab freezer challenge ❄ 🌿 . During the 6 month…
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