Last summer Huib became ill, and in first instance it appeared that he had attracted a relatively harmless infectious disease. Unfortunately, it became soon apparent that he suffered from a far more severe disease. In the past year, Huib has undergone a variety of treatments, and has done so with his usual optimism. He continued to work as much as possible and tried to keep the burden of his fight against cancer away from the people around him as much as possible. Huib was 46 years of age.
Huib was born on the 18th of December, 1973. After his high school education (1987-1993, Middelburg, The Netherlands) and reading chemistry at Leiden University (1993-1997), he commenced with his PhD research at the same institution in 1997. He obtained his doctorate in 2001 with the distinction ‘Cum Laude’ on his Thesis entitled ‘Olefin metathesis in carbohydrate chemistry: synthetic applications’. From 2001 to 2004, Huib performed postdoctoral research at Harvard Medical School where he, as a fully trained synthetic organic chemist, performed biochemical and immunological research and where he completed his academic formation.
In 2004 Huib was appointed Group Leader at the Netherlands Cancer Institute (NKI-AVL), and in 2012 he was appointed Honorary Professor at the Leiden Institute of Chemistry (LIC), Leiden University. In 2017 Huib moved to the Leiden University Medical Center (LUMC) to become Professor in Chemical Biology, and where he, until his death, supervised his research group and together with Professor Jacques Neefjes, the Department of Chemical immunology.
Huib was a highly gifted, motivated, productive and above all very creative researcher who continuously and effortlessly crossed boundaries between chemistry and biology. Indeed, such boundaries seemed not to exist for Huib in his urge to conduct inspiring and challenging breakthrough research. Huib loved to collaborate and flourished, as synthetic organic chemist, in an environment, both at the NKI and in more recent times at the LUMC, dominated by biochemists, molecular biologists, cell biologists and immunologists. Though his career was cut short prematurely, Huib’s talent, which already manifested itself during his formative years, has come to full fruition. When he started in 2004, Huib was one of the first chemical biologists in the Netherlands. In 2020 he was an international leader in this field.
Huib’s legacy is enormous and diverse. He has published numerous top-level papers on a wide array of subjects. Without focussing on a single subject – Huib made major contributions to a variety of topics in organic chemistry, medicinal chemistry and chemical biology – Huib’s name is synonymous with one single biomolecule: ubiquitin. His lab is the place worldwide that investigates, with the aid of advanced chemical probes and cleverly designed chemical-biological strategies, the complexity of protein ubiquitylation and its consequences for health and disease. Protein ubiquitylation is a central theme in cell biology and human (patho)physiology that remains poorly understood. It comprises a large and dynamic field of research and, in the fifteen years that spanned his independent career, Huib has established himself at the heart of the field, indeed on occasions has given decisive directions. His chemical toolkit, developed through organic chemistry of the highest level, for detecting and studying deubiquitylating enzymes has been instrumental to the research of many scientists and remains so until today. The study of deubiquitylating enzymes, as well as the discovery of their inhibitors for possible application in the clinic, would be close to impossible without Huib’s discoveries. Amongst others, this work has led to the establishment, by Huib, of the biotechnology start-up, UbiQ.
Possibly of even greater importance, and of major scientific elegance, is his work from more recent years: the design of chemical tools to study the enzymes that transfer ubiquitin onto proteins: ubiquitin ligases. Next to the fact that the design and development of these tools represented challenges even surpassing those for creating the ubiquitin hydrolase probes, the biomedical potential of the ligase tools is potentially enormous. Protein ubiquitylation is at least as complex as protein phosphorylation, and the corresponding ubiquitin ligase family at least as diverse as the corresponding family of phosphorylating enzymes: the kinases. The past decades have witnessed the clinical development of numerous kinase inhibitors for the treatment of various cancers. In contrast, no ubiquitin ligase inhibitors have made it to the clinic yet. Thanks to the groundbreaking work of Huib, the discovery and development of such inhibitors is now a realistic goal and in that sense the future in terms of new anticancer agents, even though too late for Huib, is bright.
Besides being a brilliant scientist, Huib was also a very enthusiastic scientist. He loved research, and he loved his colleagues within the Ovaa lab with whom he conducted his science. He maintained high standards for his students and post-doctoral researchers for whom he would walk through fire. He selected his collaboration partners with care, and devoted himself and his research group unconditionally to those partners that matched his high scientific standards. He lived for his work and enjoyed his life as a scientist to the fullest. He took pride in his achievements and was proud of the people in his group with whom he achieved his successes. He was a wonderful, inspiring, strongly opinionated but loyal colleague whom we will miss dearly. Our thoughts are with his bereaved: his partner Kori, his mother, sister, brother, family and friends.
Pancras Hoogendoorn, Dean, Leiden University Medical Center
Michiel Kreutzer, Dean, Faculty of Science, Leiden University
Jacques Neefjes, Chair, Department of Chemical Immunology, Leiden University Medical Center
Herman Overkleeft, Scientific Director, Leiden Institute of Chemistry, Leiden University