12th September 2019

Dr. Daniel Merk

Nuclear receptors are involved in countless physiological and pathological processes – from inflammations and metabolic disorders to cancer – which makes it so interesting to study their potential use in pharmacological treatments.

Why did you chose to focus your research on Nuclear Receptors?

Nuclear receptors are highly attractive targets for biologically active molecules. On the one hand, studies with several of the 48 nuclear receptors have shown that this protein family is very perceptive to pharmaceutical modulation. On the other hand, a large number of these nuclear receptors remains uncharted, which leaves us with a lot of potential for basic research and the use in the early stages of drug development. Nuclear receptors are located in the cells and often even in the nucleus itself, meaning they can only be addressed through small synthetic molecules. That gives us a very promising perspective for our research on them.

Together with other regulatory proteins, nuclear receptors form a complex network that regulates the expression of countless genes. Now, if you want to modulate this regulatory network in a specific way, you need to bind them to highly affine and very selective nuclear receptors and, on top of that, carefully consider the type and efficiency of the molecular modulation. It is very challenging to try to rationally optimize all these aspects to achieve a specific biological effect, and it is that challenge that makes it so very exciting for me to work in drug development.

Nuclear receptors are involved in countless physiological and pathological processes – from inflammations and metabolic disorders to cancer – which makes it so interesting to study their potential use in pharmacological treatments. Within the family of nuclear receptors, I am particularly interested in those related to neurodegeneration, or those that have been analyzed in knockout studies and qualified as potentially relevant for the therapeutic treatment of neurodegenerative diseases. Many of these nuclear receptors do not yet have potent modulators that could be used to study their physiological and pharmacological effects, which makes it so exciting and important to work on their development.

Is there a certain goal that you have set yourself in your research?

For all the nuclear receptors that have hardly been studied so far, I want to create as many “chemical probes” or “tool compounds” as possible. These would help us carry out comprehensive pharmaceutical studies to explore the therapeutic relevance of the receptors.

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What will the future of your research look like?

I will continue my research on nuclear receptors and focus on the mostly unexplored “orphan receptors”. I will also keep my focus on nuclear receptors with a potential therapeutical relevance in the treatment of neurodegenerative diseases.

To be able to faster characterize nuclear receptors as drug targets and to faster develop optimised ligands of this protein family, I want to use new technologies like artificial intelligence or innovative in vitro screening methods, and experiment with new forms of research collaboration.

What do you do to unwind from work? What do you do to relax?

Sports like swimming and things like reading help me stay balanced in every day life. Whenever I can I try to go to the mountains, which is where I can truly disconnect and recharge.

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What do you like about your research environment?

Frankfurt’s Goethe University and especially the Institute for Pharmaceutical Chemistry provide me with an excellent environment for my research and teaching. I like to be independent and free in my research, and still be able to benefit from the fruitful, straight-forward and very positive collaboration on-site. It allows us to create synergies between diverse professional competences, to approach research questions from different perspectives and to foster progress and innovation.