Why were you attracted to the field of experimental pharmacology?
Pharmacology was my favourite subject at university. However, my scientific and research work was fundamentally influenced by my stay at the Mario Negri Institute for Pharmacological Research in Milan, where I studied for my doctorate from 2001 to 2002. I was part of a research group that studied experimental pharmacology on cell lines with a focus on cancer, which was new to me. After my return, I managed to implement a project to build the first ever cell culture laboratory at the Faculty of Pharmacy of the University of Veterinary and Pharmaceutical Sciences, which began its operation in 2006.
What type of research did you conduct there at the time?
I built on my experience from my stay in Italy in the field of researching substances with potential anti-tumour effects. From the beginning, I focused on two areas in my laboratory: researching the effects of naturally occurring substances and newly synthesized substances. I began collaborating with colleagues from two departments at our faculty: the Department of Natural Drugs and the Department of Chemical Drugs. Karel Šmejkal was able to identify substances of natural origin that could have interesting effects in terms of antitumor activity. I spent most of my time working with substances from two plants – white mulberry (Morus alba) and empress tree (Paulownia tomentosa).
Why these drugs?
This is one of the groundbreaking approaches in cancer treatment. However, it also has its pitfalls, including the possibility of resistance development, rendering the drugs ineffective. Our goal is to investigate how these drugs might interact with other substances at the molecular level, which could potentially increase their effectiveness. Our research suggests that some naturally occurring substances may have this potential. Of course, this is only the beginning of the search for possible future applications of these properties. Our ambition is not to discover the cure for cancer as such, but we would like to open up new pathways for further research.
What brought you to this field?
Paradoxically, it is the second direction we are pursuing in our laboratory, namely research into synthetic substances that, among other things, have the ability to inhibit the STAT3 signalling pathway. This pathway is often overexpressed in many cancer cells and helps them grow and survive, making it an interesting target for future anticancer drugs. This has also opened up other avenues of research for us, such as the field of drug repurposing, where existing and approved drugs are investigated for other possible indications and new therapeutic uses. For example, there are drugs used to treat diseases other than cancer that have been found to inhibit the STAT3 pathway, and we are studying their effect on cancer cell lines.
How exactly does it work?
A few years ago, when we were just starting this research, we had a lucky break. I got an email from María Jesús Pérez Pérez, who used to be the director of the Institute of Medicinal Chemistry in Madrid. She was interested in our previously published work and asked if our group could provide her team with some research on potential STAT3 inhibitors. Their basic idea was that if we chemically combine two anti-tumour molecules with different mechanisms of action into one, we should benefit from this synergy. We were very pleased to be able to confirm their initial theoretical hybridization technology in the laboratory. It was this collaboration that led us to the idea of not looking at the substances we were studying in isolation, but to explore their potential in combination with other drugs. It turned out that the STAT3 pathway plays a significant regulatory role in anti-tumour immunotherapy. This opened up a new and large area of research, which we are currently focusing on most intensively. We have gradually expanded this research to include natural substances that also influence this pathway.
For the past few years, you have been combining scientific work with positions at the faculty management, either as the head of the Department of Pharmacology and Toxicology or as the Vice-dean of the faculty. What drives you forward?
In the past, I held three different Vice-dean positions. I wanted to give back to the faculty for what it had given me in the past – the opportunity to freely pursue both teaching and research. However, if I didn't have a great team of colleagues around me who continue the research work every day, I wouldn't be able to take on any of these leadership roles. I simply wouldn't be able to juggle everything anymore. What still motivates me in my work is interacting with students and young doctoral candidates who are constantly pushing the boundaries of science and pursuing research with the same enthusiasm I had when I started at the age of 24.
Science is exciting particularly because it brings unexpected results. Often, you set out in ten different directions, only to find that only one of them works. I also find motivation in colleagues around me, to name one, Václav Suchý, the nearly 90-year-old Rector Emeritus of the University of Veterinary and Pharmaceutical Sciences Brno, our former Dean and a great expert in the field of pharmacognosy. When I saw him recently, he was heading to the laboratory in his white coat, excited like a little boy. He told me that it is an incredibly liberating feeling when nothing is expected of him anymore and he is not under any pressure, as he was in his youth. He goes to the lab to relax and enjoy himself. I would like to achieve that one day. The circle would be beautifully complete.
