Professor Nico Callewaert
Exploring and rebuilding the eukaryotic secretory system enables new biopharmaceuticals
Abstract:
My research focuses on the development of analytical and bioengineering methodologies for the study and manipulation of processes in the eukaryotic endomembrane system and the molecules that this complex system produces. The molecules produced, endocytosed and degraded by this system regulate the contact area between all of our cells, interactions with our pathogens and balances production and breakdown of the cell’s components. Components of the system and alterations in its function are causally involved in almost all pathologies and its analysis and manipulation offers vast opportunities to beneficially interfere with disease processes. This system is also at the fundamental basis of vast areas of biomanufacturing of protein-, virus- and cell-based biopharmaceuticals.
This central theme leads us in diverse biomedical directions and work on pharmaceutical biotechnology’s most important host cell types, for several of which we have recently established the open-access standard chassis (OPENPichia, OPEN-HEK293). We have programmes in Pichia yeast biotechnology, novel-format antibody-based technology, therapeutic viral vector and cell engineering (CAR-T), as well as novel analytical technology to monitor alterations of processes in the secretory system, such as glycosylation and massively parallel studies of protein secretability. In all of our work, we push much beyond the stage of publication to bring our results as close as possible to impact for patients. I will present pieces of unpublished current work across these areas, as well as a look into what the future may bring to this field.
Short Bio:
Nico Callewaert is senior full Professor of Biochemistry and Biotechnology at Ghent University (2006-present) and research group leader at VIB (2005-present). He is currently also deputy director of VIB’s Center for Medical Biotechnology, which he founded as its first scientific director (2014-2024). In the Center, approx. 125 scientists in 8 research groups work to innovate biomedical molecular analytics and cellular bio-engineering. His lab’s approach is to enable innovative research by engineering its own novel technologies to manipulate and analyse the molecules that get secreted or otherwise released by eukaryotic cells, especially with regard to biopharmaceutical proteins and their post-translational modifications.
In terms of medically translational applications that its bioanalytical research enables, the Callewaert lab has longstanding expertise in liquid biopsy biomarker discovery based, incl. the first ‘diagnostic glycomics’ biomarkers for liver cirrhosis as predictor for liver cancer risk, and for chronic inflammatory conditions. Current bioanalytical technology development focuses on easily implementable circulating free DNA and spatial methylome profiling as well as on glycoproteomic tumor biomarker discovery.
In cellular bioengineering, Nico’s lab has 20 years of track record on pathway engineering in the eukaryotic secretory system to customize biopharmaceutical (production) cells, especially through glycosylation modifications. This resulted e.g. in the GlycoSwitch glycan humanization system in Pichia pastoris, allowing to manufacture human-like antibodies in yeast, work which is presently supported by the Gates Foundation. Other yeast glyco-engineering technology allowed to start Oxyrane (Ghent, Belgium), which developed improved lysosomal enzyme replacement therapies, and the lab continues to innovate in lysosome-targeted drug development. Current synbio projects are in glyco-engineering of mammalian cells (a.o. GlycoDelete technology, glyco-engineered CAR-T cells), massively parallel protein secretability assessment with predictive deep learning modeling, and oral delivery of biopharmaceuticals, including antibodies (startup: animab.com). Starting in Jan. 2020, together with VIB colleague Xavier Saelens, we speed-developed VHH-Fc antibodies against spots on the SARS-CoV-2 spike that are difficult to bind to by human antibodies at high affinity, building on ongoing work on influenza and RSV. Some of these are being clinically evaluated (startup ExeVir.com). Given scalable microbial manufacturability of these antibodies, the concept is deployed to other infectious disease targets, in particular to influenza.
Nico was awarded a Marie Curie Excellence Grant (2005-2009), an ERC Consolidator Grant (2014-2019) and an ERC Advanced Grant (2023-2028). Prior to his independent position, he was postdoctoral fellow and then team lead at ETH-Zürich (2002-2005) in the lab of Prof. Markus Aebi. He is inventor of more than >50 different patent families.