Chemistry on nucleic acids (DNA/RNA) diversifies its use.
Genomic integrity is continuously challenged by reactive species. Fortunately, our efficient DNA repair systems rarely miss damage, restoring more than 20,000 DNA damage per cell per day. However, DNA repair activity attenuates as we age, leading to the accumulation of DNA damage/mutations. Tragically, susceptible individuals with attenuated DNA repair activity are reported to develop cancers at a frequency of 45–85% by the age of 70.
Our team is highly passionate about studying genomic integrity and its maintanence. We, as a group of biochemists, develop biochemical measures to study and modulate the systems, looking to increase the quality of life by preventing cancer, especially for elderly.
1. Quality of DNA in your diet significantly matters
FDA recommends reductions in the consumption of cooked red meats and fried foods in general. Prevailing scientific background of the recommendation has been small molecule metabolites such as PAHs and HCAs. These are generated during cooking of foods at trace levels, and alkylate biopolymers upon consumption via bio-activation. However, National Cancer Institute (NCI) states that ‘This is NOT YET DEFINITVE’ as the carcinogenicity of these molecules has been only observed at much higher concentration compared to that in our normal diet.
We suggest that DNA in food may be an actual threat. We found that the DNA in food gets significantly damaged during cooking, of which amount is 3–4 magnitudes higher than the metabolites (damaged DNA was observed at milligram range per kilogram of meat). Upon the consumption of damaged DNA, it is digested into damaged nucleosides in stomach and guts, then absorbed and salvaged. The resulting damaged nucleotides are participated in DNA synthesis, inducing DNA repair response and mutations.
2. Enhancing the efficacy of mRNA therapeutics by regulating its translation
Messenger RNA (mRNA) therapeutics hold a great potential for preventing and treating varied genetic diseases. In the related research fields, improving stability, immunogenicity, and translation efficiency have been the desire of scientists.
Our team is interested in developing biochemical tools to improve the efficacy of mRNA therapeutics, by regulating translational efficiency, increasing stability of mRNA, and controlling the translational kinetics. Moreover, we are looking to develop post-transcriptional approach for cost- and labor-effective work flow.
3. Chemistry on AP site for versatile modification of nuclei acids
Chemical modification of nucleic acids diversifies their functions and use in research/therapeutics. However, modification of DNA/RNA is often expensive and labor-intensive. Moreover, modifying endogenous nucleic acids in cellular contexts is challenging.
We are interested in modification of nucleic acids through AP sites. AP sites contain highly reactive aldehydic sugar in its equilibrium, which can be generated through enzymatic DNA repair processes. Our aim is to develop biochemical measures to selectively generate AP sites and modifying the target nucleic acids.
In Korean… (Please see below)