Benjamin Demarco
Postdoctoral Researcher Fellow - EMBO
Contact information
Research groups
Postdoctoral Researcher
My name is Benjamin, and I was born in a tiny mining town called ‘Saladillo’ at the Andes Cordillera (mountain range) in Chile. After I finished school, I moved to Munich, Germany to start my Bachelor’s and Master’s studies at the University of Munich. During my studies, I worked as a student assistant, where I had the chance to contribute to a publication about nanoparticles and cell death (Ancona et al., Nanomaterials, 2018). Besides, I did an internship at Roche in Penzberg, Germany, where I worked in drug discovery research. I performed my master thesis in Prof. Petr Broz’s laboratory in Basel, Switzerland, where I started working on the cross-talk between apoptosis and a proinflammatory cell death called ‘pyroptosis’. I did my PhD in the same laboratory and country but in the French-speaking city Lausanne, where the laboratory was relocated.
At the beginning of this three years PhD, I contributed to a study, where we demonstrated that pyroptosis can be downregulated by membrane repair (Rühl et al., Science, 2018). After that, I continued working on how apoptosis and pyroptosis regulate each other (reviewed in Demarco et al., Immunol. Rev., 2020; Chen, Demarco, Broz, EMBOJ, 2020; Demarco et al., Mol. Cell. Oncol., 2019). We discovered that the apoptotic caspase-8 activates the pyroptotic executor pore-forming protein gasdermin-D (GSDMD) during extrinsic apoptosis. Paradoxically, apoptotic caspases-3/-7 inactivate GSDMD to damp inflammatory pyroptosis during apoptosis. These data suggest a complex pathway cross-talk that finally determines which type of death (proinflammatory or not) a cell will undergo. We also found that a channel formed by the membrane protein pannexin-1 opens during apoptosis to promote the activation of a multi-protein complex termed as ‘inflammasomes’ (Chen & Demarco et al., EMBOJ, 2019; Chen, Demarco, Broz, EJI, 2019). Inflammasome activation initiates the processing of proinflammatory cytokines interleukin (IL)-1β and IL-18 to the biologically active forms to promote inflammation. Importantly, we provided evidence that this pathway is implicated in vivo during a TNF-induced lethality model, and also during host defence upon Yersinia infection (Demarco et al., Science Advances, 2020). Finally, we found that neutrophils, but not macrophages, undergo cell lysis that requires another gasdermin protein family member (gasdermin-E), highlighting that gasdermins have a cell-type-specific function (Chen & Demarco et al., PNAS, 2021).
Currently, I am interested to further investigate in which circumstances apoptosis becomes inflammatory via gasdermin-lytic cell death and whether gasdermins contribute to sterile inflammation observed in TNF-associated diseases. I will work in Jelena Bezbradica’s laboratory for 2-3 years with the support of an EMBO postdoctoral fellowship, which starts in August 2021. I am looking forward to improving my skills as a scientist and my expertise in chronic inflammatory diseases during this postdoctoral position to further continue with a career as an independent Researcher in the future.
Recent publications
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Journal article
Demarco B. et al, (2022), Cells, 11
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Bjanes E. et al, (2021), Plos pathogens, 17, e1009967 - e1009967
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Fischer FA. et al, (2021), Proc natl acad sci u s a, 118
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Voith von Voithenberg L. et al, (2021), Proceedings of the national academy of sciences, 118, e2025578118 - e2025578118
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Chen KW. et al, (2021), Proceedings of the national academy of sciences, 118, e2101189118 - e2101189118
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Santos JC. et al, (2020), Nature communications, 11
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Demarco B. et al, (2020), Science advances, 6, eabc3465 - eabc3465
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Demarco B. et al, (2020), Immunological reviews, 297, 174 - 193
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Heilig R. et al, (2020), Life science alliance, 3, e202000735 - e202000735
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Chen KW. et al, (2020), European journal of immunology, 50, 170 - 177
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Chen KW. et al, (2020), The embo journal, 39
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Demarco B. et al, (2019), Molecular & cellular oncology, 6, 1610324 - 1610324
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Chen KW. et al, (2019), The embo journal, 38
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Rühl S. et al, (2018), Science, 362, 956 - 960
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Ancona A. et al, (2018), Nanomaterials, 8, 143 - 143