Director of the Institute of Translational Biomedicine at St Petersburg University Raul Gainetdinov: "I always wanted to work in Russia"

Could you please share what was your dream profession in your childhood? When did you become interested in science? How did you figure out your research interests?

Read the full interview in the St Petersburg University Magazine, issue No 4, 2024

I was born into a family of physicians. Since my birth, I was surrounded by medical professionals and I always knew that I was to go into medicine. However, everyone in the family was a healthcare practitioner, while I wanted something different, something more creative. I wanted to do research. Even then, I thought about experimental medicine, even though I had no idea how it is done in practice. I knew that I would go to medical university, but I would not be a healthcare professional, but a research physician. 

How did you get into the postdoctoral fellowship programme at Duke University? What did you learn from your experience of doing research in the USA?

In 1992, I defended my candidate’s dissertation and I was seeking opportunities to do science in Russia. When I finally realised that I would not be able to do research in Russia, I wrote a letter to Professor Marc C Caron at Duke University, my future mentor, whom I considered number one in the field of dopamine research in the world. He took me in straightaway. Thus, my wife and closest colleague Tatiana Sotnikova and I ended up in America. I started working at Duke University Medical Center as a postdoc. It was a tremendous experience for me, indeed. I found myself in the laboratory led by two great people, the most respected biochemists in the world — Marc C Caron and Robert Lefkowitz. I knew how to work with animals in research. At that time, there was no possibility in Russia to do advanced research using molecular biological and chemical methods. When I arrived in the USA, a genomic revolution had just occurred. For pharmacologists, it happened when the first knockout animal models were created, that is, genetically modified mice, and later rats. In the USA, Marc C Caron, as one of the world’s leading neuroscientists, quickly created several gene knockout strains. I came to Caron as a physiologist, whom he needed. The thing is that here in Russia, we know how to work with animals. In the USA, they had already moved exclusively to cell cultures and biochemical methods — they did not know how to work with animals in research. Soon, I delved into this subject and started studying genetically modified animal models. I also studied biochemistry. I mastered a great many biochemical and molecular techniques there, because there were 28 experts in biochemistry and molecular biology around me in the laboratory. I now know how to work with both animals and cell cultures in research. 

In the USA, you worked with Nobel Prize Laureate Robert Lefkowitz. De facto, you were one of his students. What did you learn from your interactions with him? 

He had a huge impact on me. Both of my teachers, Marc C Caron and Robert Lefkowitz, are incredible people — cheerful, kind, open, honest, and passionate about their work. It was a great pleasure and honour for me to work under their guidance. Of course, I learnt a lot from them. I even adopted their manner of communication. 

You have extensive experience of working overseas — in the USA and Italy. Yet, together with your research team, you chose to work in Russia at St Petersburg University. What was the reasoning behind your decision? 

I always wanted to work in Russia, but in the 1990s, it was impossible for financial reasons. I had known my colleagues overseas before I went to the USA. For quite a while, I tried to find a way to stay and work in Russia. At some point, however, it became clear that I would not be able to do research here. So, I went to America to the leading expert in our field, with whom I had already been acquainted. Then, every passing year, I would think: I am going to work a little longer in America and then I will come back home. But there was no real opportunity to come back. I used to joke that once a year I go on an eleven-month long business trip to the USA. 12 years went by like that. Yet, Tatiana and I did not feel at home in America. In terms of doing research, the USA was great, but in terms of lifestyle and culture not so... Finally, my wife and I decided to move closer to home. 

When I was already working in Italy, there were offers from the Russian Science Foundation and the Skolkovo Innovation Centre, with the opportunity to do advanced research in Russia. At that time, however, the Skolkovo Innovation Centre did not even have a single laboratory. And then, I received an offer from Rector Nikolay Kropachev. I fell in love with St Petersburg. I liked everything here very much. St Petersburg University became my home university, I am very happy to work here. For a while, I was a professor at Skolkovo, commuting to give lectures there, but St Petersburg University was my home base. It was at St Petersburg University that I received the strongest support. It is here that the laboratory was established and a vivarium was built where I keep genetically modified mice for research. In fact, here we have ideal conditions with all world standards met. 

Still, many researchers go to work overseas in the hope of better working conditions. Do St Petersburg University’s facilities enable you to fully realise your potential as a researcher today? 

In general, the conditions for conducting research are still better overseas than here in Russia, especially in the USA. In Italy, perhaps, the situation is not as good as in America. However, in the USA, the conditions are now getting worse. It is getting more and more difficult there, because the research funding in science has been cut. When I first arrived there in 1996, it was a researcher’s paradise. Today, it is not as easy to do research there as it used to be. Here in Russia, the University has created favourable conditions for me. I think I did not have such conditions even in the USA. At least in my laboratory here, I have better conditions for research than I used to have in America. 

Today, you are one of the world leaders in the field of pharmacology of the dopamine system and one of the pioneers in the study of trace amine-associated receptors. When and how did you get involved in these research areas? Why is it important to expand humanity’s knowledge in these areas? 

Dopamine is known as the "pleasure hormone". It plays a role in mood, movement and attention, and is associated with a huge number of brain disorders. In schizophrenia, for instance, there is an excess of dopamine, while in parkinsonism, there is a deficiency in it. Depression is also associated with changes in the dopamine system. When I was in my final year at the Faculty of Biomedicine of the 2nd Moscow State Medical University, I wrote my graduation paper at the Institute of Pharmacology of the Russian Academy of Medical Sciences, in the best dopamine laboratory in Russia. My research supervisor, Professor Kirill Rayevsky, was then the leading pharmacologist in Russia, whose research focus was antipsychotic drugs. Antipsychotics are dopamine antagonists — they block the D2 dopamine receptor. In my candidate’s dissertation, I explored the potential for creating novel antipsychotic drugs without side effects. Let me give you an example. There is a medication called haloperidol. This is a high-potency antipsychotic drug, with many serious side effects. Kirill Rayevsky and I were looking for less risky medications. Then, he introduced me to the leading researchers in the field of dopamine in the world. They were a tremendous source of knowledge. I became very interested in this topic. 

Then, when I was working at Duke University under my postdoc supervisor Marc C Caron, new receptors for trace amines were discovered. Trace amines are "cousins" of dopamine and serotonin. At that time, they were still unexplored. Why? Because nobody knew then that they have their receptors in humans. We knew that humans have receptors for dopamine and serotonin, but we did not know yet that we have receptors for trace amines. It was not until 2001 that receptors for trace amines were discovered. The research team that discovered trace amine-associated receptors (TAARs) came to my teachers at Duke University — Marc C Caron and Nobel Laureate Robert Lefkowitz, because they were the world’s leading experts on receptors. Caron and Lefkowitz asked me to carry out some experiments, which I did. Thus, we started studying TAARs. The topic was extremely interesting and promising because nobody knew how it works. Today, based on that research, we are trying to make new drugs. 

Then, I decided to go to work in Italy, and no one in the USA was willing or able to carry on my research, at least not at Duke. Hence, I brought the TAARs topic to Italy with me. After all, in science, it all depends on individuals. I took over this research topic at the suggestion of my supervisors, and I was making progress. Others may try to no avail, and that would be the end of it. 

Together with your colleagues from Russia and overseas, you are actively developing new medications for the treatment of brain disorders. What are your global goals in this area?

 First of all, of course, we aim to create new medications. The first drug is currently in the third phase of clinical trials in Japan and the USA. I am a consultant in these trials because I was involved in the pre-trial research. In clinical trials, you first have to demonstrate what the drug target is. That research was conducted in cooperation with the Swiss pharmaceutical company F Hoffmann La Roche. They made sure that the project is worth the investment. Here at St Petersburg University, we have also achieved significant progress. It is known that there are six TAAR receptors in humans. Studies have been conducted on TAAR1, but there is still work to be done on the other receptors. In other words, there are five more to go. That is where we are ahead of the curve! Currently, we are looking for partners willing to fund our research. 

When do you think your new medications that can dramatically improve the quality of life of many patients may appear in Russian pharmacies? 

If we are talking about medications developed in Russia, it will take six to seven years. As for the medications that are being developed in the USA or Japan, they may be launched in about two to three years. They are almost ready. Here, as I said before, a lot depends on funding. 

Last year, you became a winner of the Vyzov [Challenge] National Award for discovering fundamentally new approaches to pharmacological treatment of brain disorders. Has this had any impact on your work? Perhaps, there have been new proposals to launch production of new-generation drugs in Russia? 

Yes, this did affect my work. I have much less time now, because I am constantly giving interviews. Of course, I hope that this will draw more attention to our work and help to resolve the funding issues. We have begun negotiations — Gazprombank has shown a preliminary interest, and we are going to discuss the details. For this, I will have to make a presentation and explain the idea, because this is big money. The problem is that we need serious funding for research, and our companies do not want to risk their money. They are not yet sure that it will be worth it. All these years, the University has been supporting me. We also received a research grant from the Russian Science Foundation. Now, however, we need investors to create a drug. We are planning to approach Rosatom State Corporation. Perhaps, they will also support us. With more serious financial support, we could make faster progress in our studies. 

You have been involved in science for over 30 years. Have you ever had an urge to change your field of activity? If so, what other profession would you like to try? 

I have never felt such an urge. Even when I was a 13-year-old schoolboy, I knew that I was to become a doctor and researcher. It has never even occurred to me that I could do anything else. 

What do you like doing in your spare time? 

Like all people, I like spending time with friends and socialising. I like playing chess, and I also like going fishing. 

You make the impression of a genuinely happy person. It may be because you know very well what happiness is from a neurobiological point of view. What is your secret to happiness? 

First of all, you have to do what you love to do. That is for sure! I am fortunate that I have been living the life I dreamed of when I was 13 years old. I am just incredibly lucky! And secondly, you have to try to enjoy life more — to raise your dopamine levels.