Single cell RNA sequencing (scRNA-seq) is rapidly advancing our understanding of complex biological...
We’re excited to highlight one of the winners of the 100 Million Cell Challenge, Dr. Drew Neavin. Dr. Neavin is an investigator at the Garvan Institute of Medical Research. She recently sat down with us to discuss her innovative research on adverse drug reactions, how large-scale single cell analysis will be instrumental for unlocking genetic factors behind drug toxicity, and her ambitious upcoming project on QuantumScale.
Q: Would you tell us about your research and what drew you to single cell analysis?
Drew Neavin: I'm really interested in understanding genetics and how that influences health and disease. And I'm specifically interested in understanding if there are ways that we can use genetics in the clinic to identify patients that will respond better to certain treatments or intervene before they actually develop diseases.
One of the ways that we can look at this is with single cell approaches. Specifically, it allows us to identify genetic regulation of gene expression and use it to inform molecular processes that are happening in different diseases or environmental contexts. Single cell methods are ideal for this because we can look at genetic regulation in different cell types that have been exposed to the same environmental context. If we take immune cells as an example, we can use single cell methods to characterize how genetics regulates gene expression networks in immune cell “A” differently from in immune cell “B”. So that's really what led me to single cell: trying to understand that complex interplay between cell types, context and genetics.
Q: What questions are you hoping to address with your project?
DN: We're hoping to better understand cardiotoxicity that's induced by drugs. We know a lot of drugs, especially cancer drugs, can induce cardiotoxicity, but it's really variable between patients. Some patients will develop cardiotoxicity, some patients won't. But we don't have a good way to identify which patients are most susceptible. Unfortunately, often it’s only after a drug has been approved that some patients develop adverse events like cardiotoxicity. So the two main goals of the study are to identify individual patient characteristics that can result in drug induced cardiotoxicity and to understand the diversity of mechanisms of cardiotoxicity.
To do this, we’re developing a method that could be used during drug development that builds in the patient diversity that can then be leveraged when developing clinical trials. This will also allow us to look at a variety of different drugs known to induce cardiotoxicity in subgroups of patients, and identify different mechanisms of cardiotoxicity. We can then target different pathways for preventing cardiotoxicity that’s specific to each drug. If a patient who is susceptible to cardiotoxicity needs a specific therapy in the future, then we can pair it with a therapy that could counteract the cardiotoxicity.
Q: What attracted you to the 100M Cell Challenge?
DN: This challenge was kind of perfect for our study because it gives us the scale that we need to understand the complex interplay between genetics and cardiotoxicity, since you need a large number of individuals to do that as well as a large number of cells. In our genetic studies, we need at least 100 individuals. So all of our projects are much larger than the average single cell experimental design. It’s a power-based issue. We truly need a larger scale, in terms of samples and number of cells to be able to do these projects effectively.
Q: Would you tell us a bit about the 2 million cell project you will be running with QuantumScale?
DN: By screening 20 drugs across 200 stem cell lines, we will test 400,000 drug-gene interactions with the 2 million cells captured on the QuantumScale workflow. Importantly, we have already developed the resources that make this project possible: 200 quality-assessed stem cell lines, efficient and specific cardiomyocyte differentiation expertise and a population-scale platform for simultaneous differentiation of all 200 lines. This will be the first cardiotoxicity screen that captures genetic diversity, and the first assessed with single cell technologies, globally.
As we look to the future of drug development, Dr. Neavin's research demonstrates how advanced single cell analysis, combined with genetic insights, could transform our approach to drug safety and efficacy, ultimately leading to better patient outcomes.
We look forward to supporting Dr. Neavin’s work and its positive impact on delivering better care to patients. Learn more about the 100M Cell Challenge and the other winners.
