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S3-E35.3 – Liver Science At ILC 2022: Stellate Cells, Omics and Novel Receptor Targets

Scott Friedman, Neil Henderson and Rachel Zayas join the Surfers to discuss a groundbreaking session from #ILC2022 discussing advances in what Liver Science can tell us about fibrosis. This conversation focuses on…

Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as “one of the most exciting groups of presentations I’ve seen in many years.” This conversation centers on papers with similar methods and processes for researching stellate cells.

Scott begins this conversation by describing this process, which is based on another Nobel Prize-winning methodology. In this technique, the researchers starts by forcing an adult mature skin cell (or any cell, for that matter) o express a cluster of very well defined genes and transcription factors, which the researcher then turns into a generalized, Induced Pluripotent Stem (IPS) cell. Researchers have found ways to convert these IPS cells into stellate cells. The developer of this technique posited that it will enable us to explore the proteome.

To Scott, this process of converting a generalized cell to a stellate cell we can analyze via proteomics to find new targets is more important and noteworthy than the result of this specific study (researchers identified a novel nuclear receptor called RORalpha). To quote Scott, “they’re much closer to the action when they find a protein rather than just the mRNA that encodes it.” He goes on to discuss a second study from Insitro (a company with which he consults) about their work seeking to optimize the IPS-derived stellate cells to find the one that most closely resembles cells in vivo.

When Scott finishes, Neil notes that single-cell proteomics is not “coming, but it’s not there yet.” Neil anticipates we will have this pivotal tool available in a 1-2 year time horizon. Next, Jörn anticipates and asks about the next stage in the process: identifying a protein related to this process we can find in peripheral blood given that, as Neil noted, tissue sampling in the clinical setting will not be possible. Scott discusses a recent paper that seems to provide a solution to this issue in breast cancer. While he notes that the work has to be validated first, it clearly suggests researchers are close to finding proteins we can identify in blood in at least one cancer-related case.

From there, Scott turns to Rachel for feedback, since this is the area in which her business is building its research. Her answer has several elements to it, but the main point is that proteomic development lags behind some of the other techniques but is making rapid advances as the costs of some key analytical processes come down. She then goes on to provide a description of epigenetics, the area in which she works most intensively.

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