ACT Signature Webinars

The Complement Cascade—When Activation Mediates Toxicity

May 3, 2023 

Hosted by the American College of Toxicology

With support from: The British Toxicology Society and the Society of Toxicologic Pathology

Speaker:
Ashley Frazer-Abel, PhD, Exsera BioLabs at University of Colorado Medicine

About the Speaker:
Dr. Frazer-Abel is the Director of Exsera Biolabs on the University of Colorado Anschutz Medical Campus. Dr. Frazer-Abel specializes in complement testing for drug development and patient diagnostics. Her work in IND supporting studies started with the investigation of adverse events related to oligonucleotide therapeutics including key work to elucidate the role of Factor H in this system and how that contributed to the species-specific adverse events observed. Now Dr. Frazer-Abel is involved also involved in testing for therapeutics directly targeting complement while still working on complement-mediated immunotoxicity. As part of her commitment to expanding the confidence in and quality of complement analysis, Dr. Frazer-Abel serves as the co-chair of the International Complement Society and IUIS Committee for the Standardization and Quality Assessment of Complement Measures. Dr. Frazer-Abel has authored or co-authored over four dozen original manuscripts, numerous invited reviews, and book chapters on complement testing and standardization.

Abstract:
The complement cascade is a key component of our body’s innate immune system, protecting us from infection even at our first encounter. To act in this way complement must be nonspecific and strongly proinflammatory, meaning it also has the potential for adverse outcomes from off-target complement activation. In this webinar, we will work to demystify the complement cascade, clarify the pathways, and review which components belong to which pathway. Once we have this shared understanding, we will be able to discuss the basic functions of complement and how those functions can turn on the host and cause adverse events when the cascade is inappropriately activated. This discussion will include an analysis of the biomarkers that are useful to investigate adverse complement activation down to the specific pathway level and go further to share what is important to know when considering measuring complement, prospectively or retrospectively. We will also review what is known about complement-mediated toxicities for specific test article classes and the differences in those reactions in different species.

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