(Vienna, 17.8.2021) Together with colleagues, Artem Kalinichenko (37) discovered a novel gene defect causing a life-threatening immune disorder. Profiled as a YoungStar by St. Anna Children’s Cancer Research Institute (St. Anna CCRI), the scientist explains how to form a good hypothesis and under which circumstances he acquires aha-experiences.
Artem Kalinichenko, PhD, a postdoctoral researcher in the group of Assoc. Prof. Kaan Boztug, MD, at St. Anna CCRI investigates defects in the immune system. “In Kaan Boztug’s lab, we study real patients and the results of our work can have a direct impact on a child’s life. This is truly exciting and one of my main motivations to work at St. Anna CCRI,” the scientist points out.
He has a strong personal interest in specific immune cells, so-called cytotoxic T lymphocytes and wants to explore how these cells recognize and kill infected or tumor cells. “It is particularly fascinating how T lymphocytes distinguish between healthy and infected or malignant cells.”
The broken brakes of the immune response
In a recent study, published in the journal Blood, the scientist discovered a novel function of the protein called RhoG (Kalinichenko et al., Blood 2021). They showed that this molecule is essential for cytotoxic cells to release specific granules towards the target cells and kill them. Artem Kalinichenko and colleagues also found that mutations in the RhoG gene can cause a life-threatening disease in children called familial hemophagocytic lymphohistiocytosis (HLH). “We found that when normal RhoG function is impaired by a severe gene defect, the cytotoxic cells cannot kill their target cells. As a result, they get hyper-activated, proliferate, and release enormous amounts of signaling molecules (cytokines) that damage tissues and organs. The immune system goes crazy and cannot stop. If left untreated, the outcome of this disorder is often fatal.”
Empowering the patient’s immune system
Another project led by Artem Kalinichenko focuses on how cytotoxic T lymphocytes recognize pediatric tumors. Most of the cells in our body present different molecules (or antigens) on their surface to the immune cells. By screening these surface molecules, immune cells, such as T lymphocytes, can control whether a cell or a tissue is healthy. Upon malignant transformation, tumor cells change their metabolism and often present a new set of antigens on their surface. When T cells detect these “wrong” molecules it is a signal for them that they have found a tumor cell which has to be eliminated. “In this project, we want to identify these tumor-specific molecules and study T cells that recognize them.”
Besides that, the researchers aim to investigate how different cancer treatment strategies change the metabolism of tumor cells and, as a result, antigen presentation. “We want to know if different drugs used in the clinic can either improve or impair tumor recognition by T cells. Consequently, we might be able to instruct clinicians on how to select the drugs and their combinations for the specific types of cancer. Empowering the patient’s immune system to recognize tumor cells even more efficiently may help to improve the treatment.”
How to find the missing piece of the puzzle
When asked about how to deal with challenges in research, Artem Kalinichenko states, “One of the major requirements is to be resistant to negative results and think positively. It is sometimes tough to accept that the hypothesis you had – and spent some time proving – is wrong. But this is how science can go. Getting a negative result is not always bad. It is still a result, and often very important. You generate a new hypothesis and continue. That is what I had to learn early in my career. Of course, this process can be quite time-consuming, so you better have a good hypothesis in first place.”
But how do you come up with a good hypothesis in the first place? “There are no golden rules or protocols. You have to read a lot, sort out important information, and finally talk to your colleagues and discuss ideas. This exchange with your colleagues and other scientists is probably the most important and exciting part. You often get the missing pieces of your puzzle from such discussions.” In addition, Artem Kalinichenko often relies on “his gut feeling” when it comes to making the important decisions. “Of course, it is a hard work that needs a lot of creativity and dedication. We often do preliminary experiments, to find the hints and confirmation for our ideas. Once you are on the right track, you need to go full speed.”
Another challenge for Artem Kalinichenko is that research is not a fast process. Some things can be dynamic, but others require time. “It can be difficult to speed things up even though you know you are going the right direction. Being patient and taking my time to perform experiments wisely and thoughtfully, is the way to go. My favorite motto here is: Fast is slow, but without breaks.”
However, these obstacles cannot prevent him from passionately searching for new results. “My motivation comes from natural curiosity. I just can’t stop thinking of my research, and that is what drives me forward no matter what.”
Think wide to be creative
Even in his free time, Artem Kalinichenko never stops thinking about his experiments. “As a person who easily gets excited and involved in many things it is really tough to balance my family life. My wife is also a scientist. She does research in the field of plant immunity. At home, we often end up discussing scientific topics, ideas and plans. Talking to people from a different field of research is a great way to keep your vision and thinking wide. Interestingly, some findings relevant to humans have been discovered in plants first, like RNA interference. Plant researchers found that specific flowers could change their colors due to RNA interference. Since then, this mechanism of gene down-regulation has been demonstrated to exist in many other organisms, from flies to humans, resulting in the award of the Nobel Prize, but unfortunately not to those plant scientists who first discovered RNA interference.”
About Artem Kalinichenko, PhD
Artem Kalinichenko, PhD, is a senior postdoctoral researcher in Kaan Boztug’s group at St. Anna Children’s Cancer Research Institute and the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases in Vienna, Austria (previously also affiliated to the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (ÖAW) in Vienna). During his first Postdoc he worked in the lab of Gennaro De Libero, MD, PhD, in Immunology at University Hospital Basel, Switzerland. Artem Kalinichenko has pursued his PhD research at the Institute of Bioorganic Chemistry RAS in Moscow, Russia, and the Institute of Protein Research in Puschino, Russia. He obtained his PhD in Biochemistry from A.N. Bach Institute of Biochemistry in Moscow, Russia, and his Master of Science in Microbiology at the Udmurt State University in Izhevsk, Russia.