"There are probably many more discoveries and surprises to come"

17 July 2023

Dr. Bálint Lippai is 27 years old, a first-generation doctor, whose ancestors are mostly teachers. He comes from Seregélyes, a village with 4-5 thousand inhabitants, and attended secondary school in Székesfehérvár. As a secondary school student, he came upon the "Tudomány, ami összeköt" competition in Pécs. He wrote about proteins in his essay, which made it to the finals, and as a reward he participated in the university preparatory camp for secondary school students. He decided then that he will continue his studies at the Medical School in Pécs. Both the atmosphere of the camp and the city played a big role in this, he was welcomed by a great team spirit at the university and was also captivated by Pécs. He is a PhD student at the Department of Biochemistry and Medical Chemistry and is working at the Szentágothai János Research Centre as a member of the department's outsourced research group. His supervisors are Dr. Ildikó Bock-Marquette, junior research professor at the Department of Biochemistry and Medical Chemistry and the Szentágothai János Research Centre, and Dr. Péter Bakó, senior lecturer and deputy director at the Department of Otorhinolaryngology.

 

Written by Rita Schweier

 

"The fact that I am still working with proteins is more of a coincidence than anything else, although it was the subject of my secondary school essay as well. These molecules have many functions in our bodies, from the structure to intercellular signalling. I was interested in otorhinolaryngology, in which my childhood otorhinolaryngologist played a big part, and then I got the head and neck region during my anatomical dissection practice by chance, which brought me even closer to this field. During my otorhinolaryngology classes at the clinic, I approached Dr. Péter Bakó, my current supervisor, that I was interested in the field in more depth and would like to work on a research project in the frame of the Undergraduate Research Society (TDK). At the time, he and Dr. Ildikó Bock-Marquette were working on an animal model for the study of tympanic membrane perforation, which is how I encountered basic research. Tympanic membrane perforation is a major cause of conductive hearing loss. Approximately eighty percent of perforations close spontaneously, but twenty percent become chronic. The solution is surgical, but several newer approaches are being tested worldwide. One such approach is the use of bioactive substances, which greatly aid healing. More experiments are being directed towards fibroblast-derived growth factors as well, which also contribute to tissue healing processes. Our research with the thymosin beta-4 peptide is part of this new trend," he says.

Bálint Lippai is part of the research team led by Dr. Ildikó Bock-Marquette, who received a prestigious international lifetime achievement award for her work on the same peptide recently. Her research has shown that the protein could represent a revolutionary breakthrough in the treatment of various cardiovascular diseases. The role of the peptide is being further studied, as the molecule's efficacy is complex, and it is hypothesized that it may also facilitate tissue and organ regeneration in other organs.

Bálint Lippai has been passionate about this area since the end of the fourth year. He participated in the competitions of the Undergraduate Research Society, where he achieved good results. As a sixth-year student, he won in his section, which qualified him for the National Scientific Students’ Associations Conference. He is a board member of the Hungarian Medical Association of America’s Hungary Chapter, they hold an international conference every year in Balatonfüred. In 2020, he won the first prize for his presentation on his project about the regeneration of the tympanic membrane, which earned him a trip to the parent organization's congress in Sarasota, Florida last year. In the meantime, as their research progressed, they presented their project in Rome at the 6th International Symposium on Thymosins in Health and Disease, a biennial conference on the thymosin protein family organized by those who discovered the protein.

"Basic research gives you a very good perspective and critical thinking, which is essential for complex patient care as well. In addition to our experiments towards the regeneration of the tympanic membrane, we are studying the presence and possible role of thymosin beta-4 in the development of the auditory sensory organ in mice. In addition to basic research projects, we are currently working closely with the clinic, processing human tympanic membrane samples from head and neck surgical materials with ethical permission. When collecting the samples, I can observe the surgeries, so I can directly see the process of the interventions," he explains.

Surgeons perform complex head and neck surgery procedures in ear tumour surgeries. These involve closing the tympanic cavity and removing the healthy, intact tympanic membrane. These removed tympanic membrane tissues are used in research with the patients' consent. The tympanic membrane not only plays an important role in hearing but also acts as a barrier, sealing the tympanic cavity and preventing infections.

As he says, the tympanic membrane sample is prepared under a microscope in the laboratory and then placed on collagen gel saturated with a cell culture medium. The tympanic membrane cells then divide and migrate into the gel. Half of the cells are treated with the medium only, while the other half are treated with the thymosin beta-4 peptide. The migration of the cells and their rate of replication is monitored by daily photographic documentation. Each sample is subjected to various immunostaining procedures or RNA is isolated from them and sent for further analysis. This can reveal how the protein affects the cells of the tympanic membrane.

"Our idea is that if the protein has a strong regenerative effect on the heart, this could also be true for the tympanic membrane. The peptide has been shown to have beneficial effects in other organs as well, such as in the treatment of corneal injuries and bacterial infections and is also used in certain types of bandages for healing skin injuries. Interestingly, the cornea and the skin have the same embryonic origin, both being ectodermal, as is the outer layer of the tympanic membrane. We have shown in animal models in the case of the tympanic membrane as well that the protein enhances both cell migration and reproduction, and we have also observed a positive difference in certain stem cells. Our results on these were published in February this year. In addition to studying the development of the ear, we plan to look at the layers and stem cells of the tympanic membrane from the perspective of healing processes. There are probably many more discoveries and surprises to come," he says.

He adds that although there are many research groups around the world working with the peptide family, the research group at the Medical School in Pécs was the first to describe the molecule's implications in the field of otorhinolaryngology. The next international thymosin symposium will be held in Washington in 2024, where he hopes to present new results of both their studies on the tympanic membrane and their developmental experiments.

As a second-year PhD student, he sees research as something that can only be stopped, not finished because newer and newer ideas and discoveries flow during creative experimental work. This inspires him, so he does not want to stop participating and collaborating in basic research even if he later focuses on clinical work. He would be most happy if his research could be used in everyday practice in the future, but in the meantime, he is driven by the joy, novelty and unpredictability of discovery, and the experience of brainstorming with fellow researchers. He is not deterred by the fact that this field is far less well-financed than clinical work either. In addition to the multicultural environment and the team spirit, he is grateful to learn a lot of new things, which is supported by the university in many ways. He is also happy to have mentors, rather than bosses, who he can always count on. He is thankful to his colleagues in the laboratory and to the staff at the Department of Pathology who help him with histological sample processing.

Photo:

Dávid Verébi (UP MS)