Multiomic analysis of serum and exosomal biomolecules associated with total body irradiation

Wojciech Fendler, MD, PhD, Associate Professor carries out a project financed by a grant from the “OPUS 17” competition of the National Science Center.

The human body exposed to high doses of radiation irreversibly loses the ability to produce circulating blood cells, which in a short time leads to death. This is due to multi-profile damage of the bone marrow stem cells, which die when exposed to radiation. The harmful effects of radiation on the body are associated with the formation of free radicals that destroy cells and direct and indirect damage to DNA – the genetic material of cells. These mechanisms are used during oncological radiotherapy, but the radiation dose is precisely determined and administered so as to maximize damage in the diseased tissue, while protecting nearby organs. On the other hand, the intentional exposure of civilians to radiation is a serious threat in the era of global terrorism.

In the case of a terrorist attack using radioactive substances (“dirty bomb”), failure of atomic reactors leading to contamination of the environment with radioactive material or failure of oncological radiotherapy equipment, the dose that the human body receives is often unknown. Lack of knowledge about the dose of radiation absorbed by the body results in numerous difficulties in providing them with adequate care. People exposed to high doses of radiation must receive a bone marrow transplant to survive, while those exposed to lower doses usually only require symptomatic treatment. Unfortunately, guessing immediately after the event who received what dose of radiation exceeds the capabilities of conventional diagnostics. Usually, only after 3-7 days, when signs of radiation sickness appear, it is possible to qualify patients for bone marrow transplantation.

This project aims to propose a solution that allows faster diagnosis of exposure to high doses of radiation and to improve the qualification of patients for transplantation or symptomatic treatment. For this purpose, microRNAs (short fragments of nucleic acid present and stable in human serum) will be used. During the project, we will examine the quantity and types of all microRNAs present in the blood of people undergoing high-dose therapeutic irradiation during the bone marrow transplant procedure. This will allow the microRNA-based diagnostic test to be adapted for potential use in clinical settings.

Then, to discover the mechanisms of response to ionizing radiation, research will be conducted in collaboration with Harvard Medical School to characterize microRNAs associated with radiation exposure in exosomes – vesicles actively secreted by cells. Determining the microRNA profile in exosomes and superimposing this information on proteomic data and characterizing proteins present on the surface of extracellular vesicles is one of the project’s objectives. They will allow to determine the tissue origin of exosomes secreted in response to radiation and will allow to identify or predict the functional significance of radiation-related microRNAs.

Multiomic analysis of serum and exosomal biomolecules associated with total body irradiation
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