川崎症
I am interested in vascular inflammation-related diseases which are characterized with leukocyte infiltration through the vein endothelial layer. To have a good experimental tool, since 2017 we have spent much time in developing the in vitro leukocyte-transendothelial migration (LTEM) assay to evaluate the severity of leukocyte infiltration. In 2018, by analyzing multiomics data (gene expression and DNA methylation) of Kawasaki disease (KD) patients, we found that S100A gene family were hypomethylated in DNA, enhancing the activities of S100A8/A9/A12 in KD. Using LTEM assay, we confirmed that the proteins of S100A8/A9/A12 promoted in vitro neutrophil infiltration through coronary artery endothelial cells, which was consistent with the mechanism of KD complication, coronary artery aneurysm (Clin Epigenetics. 2018 Nov 1;10(1):135). Using this LTEM assay, we also identified that miR-182-5p was a biomarker of KD complication and enhanced in vitro neutrophil infiltration in KD (Mol Genet Genomic Med. 2019 Dec;7(12):e990). In addition, by using iTRAQ gel-free proteomics, we analyzed serum samples and developed a serum protein-based KD biomarker panel, facilitating the timely prediction of Kawasaki disease. We also found that S100A12 enhanced the intensities of cell adhesion molecules of neutrophils. As a result, S100A12 promoted neutrophil infiltration which could be attenuated with S100A12 antibody treatment (Sci Rep. 2020 Sep 24;10(1):15645).
ADHD
Another research interest is attention-deficit/hyperactivity disorder (ADHD), which is diagnosed based on clinical manifestation without reliable molecular biomarkers. In 2018, we developed a miRNA biomarker panel to facilitate the prediction of ADHD (Front Psychiatry. 2018 May 29;9:227). We got the patent based on this technology in many countries. And this patent has been transferred to 賽亞基因 to develop commercial diagnosis kit. In 2019, we found that several of these miRNA biomarkers were associated with the gray matter volume (Eur Arch Psychiatry Clin Neurosci. 2020 Dec;270(8):1037-1045), implying their roles in neuron development. In 2022, by increasing the sample size, we confirmed our ADHD miRNA biomarker panel and enhanced the overall performance (Transl Psychiatry. 2022 Feb 19;12(1):67). In addition, with in vitro cell model, we concluded that miR-140-3p and miR-126-5p promoted the differentiation of neuron cells by repressing apoptosis and/or necrosis pathway.