How did you get interested in Medicinal Chemistry?
I got interested in chemistry quite early, around the age of ten. At that time, however, I was more fascinated by, let's say, the reactions of compounds in high oxidation states. Later, towards the end of secondary school, I became more and more interested in the interactions of chemical compounds with biological systems, which was also partly due to my very passionate chemistry teacher who always established a link between chemistry and biology. When I started studying chemistry, it was already clear that I wanted to specialize in Medicinal Chemistry or Chemical Biology later on.
Where and when did you obtain your PhD diploma?
After studying chemistry in Karlsruhe, Heidelberg, and Montpellier, I went to Tübingen University to join the group of Prof. Stefan Laufer where I obtained my PhD in 2014. My main project aimed at the synthesis of non-covalent and covalent inhibitors of Janus kinase 3 (JAK3).
Where did you have your postdoc position?
I did my postdoc in the group of Prof. Karl-Heinz Altmann at ETH Zürich. I had a great time working on the total synthesis and investigation of the molecular mode of action of mycolactones, a class of natural products known as the virulence factors of Mycobacterium ulcerans causing the neglected disease Buruli ulcer.
What are your current research interests?
Most of my research centers on targeted covalent inhibitors for protein kinases as well as the chemistry enabling covalent targeting approaches. My group is also working on some other target classes including HECT-type E3 ligases. Currently, my major focus is on the development of chemical probes for understudied targets, but I'm also aiming for more translational research projects.
What do you like best about your work?
The diversity of challenges, the freedom to choose my own research fields, and the possibility to discover new things every day.
What kind of tasks does your work involve?
Research, teaching, leading a team, acquisition of funding and, unfortunately too many, administrative tasks.
What kind of skills does your work require?
Many! Curiosity is probably the most essential one but knowledge, creativity, critical thinking, commitment, persistence, social-, communication-, and team leader skills as well as intuition are also quite important.
What do you consider your greatest achievement in your scientific career?
I think that one is still about to come. :)
Which of your papers are you most proud of and why?
I've been involved in many interesting projects resulting in publications on covalent inhibitors for kinases like JAK3 and BMX, but also on the elucidation of the molecular mechanism of the neglected disease Buruli ulcer. Still, the paper I'm most proud of is my Perspective article on covalent "warheads" published 2019 in J. Med. Chem. It took me a lot of effort to write this paper but once it was published, it really received much attention in the community, and I received very positive feedback. At the end, it was absolutely worth the investment!
How many PhD students and postdocs do you currently supervise? Are you currently looking for a new PhD student or a postdoc?
I'm currently supervising four PhD students and one postdoc. I'm always happy to receive interesting applications, but I cannot offer any funded positions at the moment.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
In the first months of my PhD thesis, I made a few beginner's mistakes. For example, I was a bit overambitious in scaling up a heterocycle chlorination reaction to generate larger amounts of my core scaffold. Unfortunately, a 2L beaker full of ice wasn't enough for quenching 300mL of phosphoryl chloride and it came to a runaway reaction. Cleaning the fume hood was awful! Around the same time, I also had a little accident spilling a portion from a large-scale Parikh-Doering Swern oxidation. You can imagine that my popularity in the lab wasn't very high on that day!
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I can recommend the #MedChemCASES webinars organized by the GDCh Medicinal Chemistry Division's NextGenMedChem group (which I'm glad to be part of)!
Which field of medicinal chemistry do you consider the most promising for the future?
I would not dare to select only one. We are currently seeing a rise of new enabling technologies such as cryo-EM, DNA-encoded libraries, AI-driven drug discovery and protein structure prediction and substantial advances in chemoproteomic profiling techniques, which I expect to trigger significant transformations in the field. Moreover, novel modalities like molecular glues or PROTACs open new targeting paradigms and expand the scope of what we consider druggable. At the same time, I think a lot of discoveries remain to be made in traditional target families. If you consider, for example, that so far roughly a third of the human kinome is severely understudied and the same applies to many other target classes, this suggests that a lot of "hidden treasures" are still waiting to be discovered.
What would you expect to be the next major breakthrough in medicinal chemistry?
If I could predict that, I would be rich! I think medicinal chemists will keep pushing the boundaries in many different areas and emerging technologies like cryo-EM, CRISPR-Cas or AI will facilitate this process. One thing I'm definitely very excited about is the outcome of the ongoing clinical trials with the first PROTAC degraders.
