How did you get interested in Medicinal Chemistry?
During my chemistry studies I first fell in love with synthetic organic chemistry. Synthesizing and characterizing organic molecules was something I enjoyed a lot. In the course of my studies I then became attracted by the logic of retrosynthesis and natural product synthesis, which was then also the topic of my PhD thesis. Naturally, once you have synthesized complex organic molecules you also become interested in their pharmacological activity and the broader context of drug targets as well as pharmacokinetics.
Where and when did you obtain your PhD diploma?
I obtained my PhD from Karlsruhe Institute of Technology (KIT) in 2006. During my undergraduate studies at University of Bonn, I decided to join the group of a freshly appointed organic chemistry professor, Stefan Bräse. Stefan was an outstanding mentor, giving every team member the feeling of pushing the boundaries and providing every support. Shortly after I joined the group, Stefan was appointed to KIT and I moved with the group.
The topic of my PhD project was the total synthesis of the fungal natural product Diversonol which forms part of a larger group of fungal metabolites. Our goal was to apply a self-developed synthetic method to this group of natural products which in the end worked out. We published the total synthesis in Angewandte Chemie and the work was later confirmed by the Nicolaou group in an independent synthesis. Unfortunately, Diversonol turned out to have very limited biological activity, but this is also part of science.
Where did you have your postdoc position?
For my postdoc, I had the opportunity to join Andy Myers’ group at Harvard University. This was a different universe and an enormous learning experience. Over the last few decades, Andy´s group has had an immense influence on the broader field of Life Sciences. As one example, the group´s work on several classes of antibiotics has clearly highlighted the power of small molecule drug discovery. What I found particularly impressive was the combination of synthetic organic chemistry with chemical biology as well as the commitment to push translation of inventions into clinical development via startup companies.
Where are you currently working and what is your current position?
I just recently started a new position within Bayer Pharmaceuticals as Head of Process R&D. In this role, I work with a talented team of chemists to push drug candidates into clinical development via chemical route optimisation and scale-up. Interestingly, this includes both small molecule candidates as well as new modalities such as protein conjugates or peptides.
Amongst other topics I am very interested in chemistry at the interface to other disciplines and modalities. To me, there sometimes has been a too reductionist view on organic chemistry as being focused on small molecules. In reality, breakthroughs in gene editing or modalities such as mRNA offer unique challenges and potential for organic chemists and chemical biologists.
How would you explain what your research area is to non-scientists?
I normally start by talking about diseases that everybody knows such as Covid-19, bacterial infections or different cancers. People then understand the context and societal relevance. Probably most of us have experienced the devastating impact of such diseases in our families and this creates a huge motivation to work in the pharma industry. I then also explain that drugs need to be synthesized in efficient amounts and quality in order to help patients.
What do you like best about your work?
First I like the relevance and purpose. Looking at the still large unmet medical need for many diseases and having witnessed the impact of disease in my family I do not need any additional motivation. Second, I like the breadth of scientific challenges which you find in a global company like Bayer. And third, I enjoy working with great colleagues from which I also learn a lot.
What kind of tasks does your work involve?
There are a variety of tasks that also varies over time. Let me focus on two examples: One task is to steer a portfolio of projects with my team. Here, we need to make sure that the projects keep their timelines during preclinical and clinical development and that we deliver CMC packages that meet regulatory requirements. The second task is to take a strategic view on my team and define where we need to adopt novel technologies and/or further develop our expertise.
What kind of skills does your work require?
To me, leadership and communication skills are essential. As a young student, I was very motivated by my PhD advisor who was a role model and mentor to me. The same should hold true for every leader, i.e. understanding the individual needs of your coworkers and providing a work environment of trust and honesty. Communication skills are also very important in today´s complex working environment. Here I would also add emotional intelligence: communication is not only talking but also carefully listening. Of course, scientific expertise also matters so that you can discuss on eye-level with other scientists and have a credible voice.
What do you consider your greatest achievement in your scientific career?
For the last 10 years, I have been a lecturer for medicinal chemistry and agrochemistry at KIT and Freie Universität Berlin. Over the years, several students became attracted to the field due to the lectures and some even started their career in industry. This makes me very happy and proud.
Which of your papers are you most proud of and why?
During my PhD thesis I accomplished the total synthesis of the fungal metabolite Diversonol together with a lab colleague which we then could publish in Angewandte Chemie. It was a great experience synthesizing a molecule that had never been synthesized by humans before and being able to publish the synthesis in a high-ranking journal.
What are the features of a successful PhD student or postdoc?
From my point of view there are several important features for any scientist: an intrinsic motivation and joy working on scientific projects that also helps to overcome unavoidable drawbacks. A critical mindset that allows to critically judge scientific results from yourself and others. Creativity in problem solving that helps to identify new avenues and solutions. And then let´s not forget communication: Being able to present scientific work to others with a focus on the audience is a sometimes underestimated skill.
What advice would you give to someone who wants to know more about your field?
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Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?
Of course there will always be situations that from a personal judgement one considers unfair. But when it comes to outright discrimination or mobbing, my clear advice would be to speak up and leverage escalation that should be in place in every organisation.
What would you like to ask from other medicinal chemists?
First I think we all need to play a more active role in communicating what we are doing and the impact our work has on society. Second, we need to constantly build on breakthroughs in other disciplines and broaden our repertoire of modalities. Examples like Protacs and mRNA clearly show that there is ample of opportunity for medicinal chemists to constantly push the limits of drugability.
What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?
During my postdoc I was working with larger amounts of triflic acid during a scale-up campaign. I had chosen a cannula with an insufficient diameter and it was not properly affixed to the syringe. This caused a major spill – fortunately inside the fume hood. A colleague immediately helped me to neutralize the spill with bicarbonate solution.
Which field of medicinal chemistry do you consider the most promising for the future?
In general I think there is tremendous opportunity in the area of new modalities. It is still early days in areas like protacs or RNA targeting but I believe we will see many exciting advances in the future. Then let´s not forget the potential of small molecules in the context of precision medicine.
What would you expect to be the next major breakthrough in medicinal chemistry?
One area that I would like to highlight is selective tissue targeting. This is a problem largely unsolved for most modalities and once solved it has the potential to deliver superior outcomes. There is a lot of exciting work ongoing in early R&D and I am optimistic that we will see breakthroughs at least mid-term.