You tend to focus in your scientific investigations on neuronal regeneration. Why is this subject so important?
The number of patients suffering from nerve damage grows every year. Regrettably, once the peripheral nerve is lacerated, in most cases, full recovery of the lost sensory and motor functions is rarely achieved due to the complex anatomical structure of the human body and the inhibitory effects of the extracellular environment of the nerve tissue on neuronal repair.
What methods are used in the treatment of peripheral nerve injuries?
These can include ‘end-to-end’ nerve suture, autotransplantation, and transplantation from a foreign donor. In the last twenty years, researchers have focused on replacing these conventional methods of treatment with approaches that take advantage of advances in biomedical engineering. The most promising research direction in tissue engineering and regenerative medicine is the design of neural implants. Recent advances in molecular biology and neuroscience have helped discover effective tools for neural cell regeneration.
What do you hope to achieve in your current research?
We intend to develop a neural implant which can release molecules that induce changes in gene expression (this is the process by which functional products, mainly proteins, are produced in the cells of our body). Naturally, in the center of our attention are genes that are critical for neuronal regeneration. Recent studies indicate that DNA demethylation promoted by methylcytosine dioxygenases, TET enzymes (Ten-eleven translocation methylcytosine dioxygenases), is the primary mechanism involved in reprogramming the cellular states of mature mammalian neurons to enable nerve fiber growth.
Could you explain DNA demethylation and its role in simple terms?
From conception through to death, controlled methylation and demethylation of DNA occurs in our cells to regulate the expression of specific genes, among other things. Put in the simplest terms, these two are the processes of tiny modifications to individual, precisely selected 'building blocks' in the chain of our genetic information. These modifications are necessary for the activation and deactivation of fine-tuned cellular programs that determine the fate (e.g., the regenerative potential) of the cells that make up different types of tissue. Demethylation is the reverse of methylation. It reboots the expression of certain groups of genes. To understand the mechanisms that promote effective regeneration of peripheral axons, we intend to conduct a full-scale study of the changes in gene expression following the introduction of DNA demethylation-inducing biomaterials into cultured neural cells in vitro and an animal model in vivo. It is important to bear in mind that there are multiple levels of gene expression regulation and that they are extremely complex processes.
What do you expect to find?
We hope that the results of the project will help, within a timeframe that is difficult to define today, pave the way for the development of new therapeutic methods for the recovery of the lost sensory and motor functions following peripheral nerve transection. This assertion is supported by the highly promising findings of the preliminary studies that my group and I conducted in the preparatory phase, in the course of previous research projects under my leadership.