Uncovering the secrets of inflammasomes

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Mohamed (Mo) Lamkanfi made the jump from academia to industry a mere eight months ago, to pursue a career with the Janssen Pharmaceutical Companies of Johnson & Johnson, as Head, Innate Immunity, based in Beerse. Presenting his research at scientific symposia and the recently organized joint Crown Bioscience – Janssen symposium on Immuno-Oncology and Inflammation, Dr. Lamkanfi held the audience’s attention with his expertise on inflammasomes and in-depth knowledge of these complex multiprotein structures.

By Amy LeBlanc

Knowledge of inflammasomes, and their immunological role, is still very much in the developmental stages. Discovered as recently as 2002, by the team of Dr. Jürg Tschopp at the University of Lausanne, inflammasomes have proven to be important drivers of human inflammatory responses. Composed of several proteins, inflammasomes drive immune responses by promoting the maturation and secretion of pro-inflammatory cytokines interleukin 1β and interleukin 18. In addition, they induce a proinflammatory cell death mode called pyroptosis that promotes secretion of these cytokines in circulation; distinct from apoptosis, which often suppresses inflammation. In short: inflammasomes activate an inflammatory cascade of huge importance to auto-inflammatory, auto-immune, infectious, neurodegenerative diseases and malignancies.

When things go wrong

Inflammasome signaling is being investigated by researchers, such as Dr. Lamkanfi, as it has been shown that polymorphisms and mutations in inflammasome genes are linked to both rare and common autoimmune disorders. Diseases such as type 2 diabetes, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, cancer, etc.; all have been linked to inflammasomes via excessive or deficient secretion of pro-inflammatory cytokines. Mutations, an unhealthy diet that disbalances the gut microbiome, air pollution, cigarette smoke and diverse other environmental factors may be to blame for the dysregulation of the inflammasome, but more research is still needed into these underlying mechanisms before such knowledge may be translated into solutions.

Lamkanfi’s work has been fundamentally important to the growing understanding of inflammasomes and their function in the body. Born in Antwerp and educated at Ghent University, Dr. Lamkanfi spent his early post-doc years in the US working at the University of Michigan and the biotechnology company Genentech. Upon returning to Ghent in 2009, Lamkanfi became professor of Molecular Immunology at Ghent University and a Group leader at the Flanders Institute for Biotechnology (VIB), where his lab specialized in inflammasome function. Over the years, Lamkanfi has authored over one hundred papers on inflammasome research, including multiple groundbreaking publications in Nature and Cell press journals. He received several recognitions and awards for his research, including several grants from the European Research council (ERC); the Prize of the Flemish Scientific Foundation for Biomedical Sciences (2013); the AstraZeneca Foundation Prize for Auto-immune diseases and Rheumatology (2014); the Baillet Latour Grant for Medical Research (2016), and the Laureate of the Royal Belgian Academy of Sciences and Arts (2017).

Read more about the scientific partnership between Janssen and UZ Gent/UGent here

Finding solutions

Eight months ago, Lamkanfi made the shift back into industry, when he took up employment with Janssen in Beerse. Today, his work still revolves around fundamental immunological research, with an immediate focus on inflammasome biology and cell death pathways. In particular, he studies a specific type of inflammasome sensors, so-called NOD-like receptors (NLRs). NLRs are a family of intracellular receptors, used by immune and stromal cells to detect when to mount an immune response against potential invading pathogens. By understanding the underlying activation and signaling pathways of NLRs, Lamkanfi looks to find solutions to numerous diseases such as cancer, neurodegenerative diseases and chronic inflammatory diseases.

The continued commitment to immune research by top-tier scientists such as Dr. Lamkanfi will hopefully soon result in new solutions for patients. Inflammasome research fits perfectly into Janssen’s goal of creating transformational medicines to prevent, intercept and cure diseases with high unmet need. By deepening the knowledge of NLRs and inflammasomes, it may be that Dr. Lamkanfi and his colleagues contribute to the development of innovative therapeutic approaches for cancer, neurodegenerative and chronic inflammatory diseases around the globe.