劉宗霖 教授

學群：生物醫學科技產業學群

研究專長：生物資訊、基因體組序、環境微生物分析

E-mail：tsunglin@mail.ncku.edu.tw

研究室：89904

研究室Tel：+886-6-2757575#58223

實驗室Tel：+886-6-2757575#58234#911

生物資訊是一門應用資訊技術來準確與有效地分析生物資料的跨領域學問。在次世代定序技術問世後，生資領域因需處理大量不同生物資料更蓬勃發展。在生資課題中，我們專注在微生物基因體學和免疫基因組分析。微生物基因體學探討不同環境下的微生物群落，像是人體各部位、土壤和水體等。我們和臨床醫師合作，探討鼻腔菌相與兒童氣喘的關係、口腔菌相與漱口水的關係以及腸道菌相與腸躁症的關係。我們已找出許多和疾病相關的重要菌屬。免疫基因組分析透過追蹤Ｔ細胞獨特的受器序列（TCR）來探討Ｔ細胞的多樣性。獨特的TCR序列是藉由VDJ重組而產生，而非重組的TCR序列通常被認為是無用的，因為它們無法轉譯成蛋白質。但我們發現非重組序列可以作為Ｔ細胞淋巴癌的生物標誌。我們正在探索非重組序列更多其它的功能。

	Clonality assessment, which can detect neoplastic T cells by identifying the uniquely recombined T-cell receptor (TCR) genes, provides important support in the diagnosis of T-cell lymphoma (TCL). BIOMED-2 is the gold standard clonality assay and has proven to be effective in European TCL patients. However, we failed to prove its sensitivity in Taiwanese TCL patients, especially based on the TCRb gene. Interestingly, we found a higher percentage (>81%) of non-recombined TCRb sequences in a TCL patient with a negative BIOMED-2 test. This suggests a new TCR target for enhancing TCL diagnosis. To further explore the hypothesis, we proposed a cost-effective digital PCR assay that quantifies the relative abundance of non-recombined TCRb sequences containing a J2-2P~J2-3 segment. With the digital PCR assay, bone marrow specimens from TCL patients (n=9) showed a positive outcome (i.e., the relative abundance of the J2-2P~J2-3 sequences ≧5%), whereas non-TCL patients (n=6) gave a negative result. As five of nine TCL patients had a negative BIOMED-2 test result, the J2-2P~J2-3 sequences may improve TCL detection. This is the first report showing the capability of characterizing non-recombined TCR sequences as a supplementary strategy for the BIOMED-2 clonality test.
	Airway and gut microbiota are important in asthma pathogenesis. Although several studies have revealed distinct microbiota in asthmatic airways at baseline compared to healthy controls, limited studies compared microbiota during acute exacerbation (AE) and in the recovery phase (RP) in the same asthmatic children. We aim to investigate association between microbiota and asthma status in children and explore their relationship with clinical features of asthma. Using 16S rRNA sequencing, we found that most nasal microbiota were dominated by only one or two of six bacterial genera. The domination was associated with mite allergy and patient age only during AE but not in the RP. When moving into RP, the relative abundance of Staphylococcus increased while that of Moraxella decreased. Throat and stool microbiota were not associated with most of the clinical features. Interestingly, stool microbiota during AE was associated with ABO blood type and stool microbiota in the RP was associated with frequency of the subsequent exacerbations. In summary, the association between nasal microbiota and mite allergy only during AE suggests an altered local immunity and its interplay with nasal microbes. Our work provides a basis for studying microbes, and prevention or therapeutic strategy in childhood asthma, especially during AE.
	Chlorhexidine (CHX) and essential oil containing mouthwashes like Listerine® can improve oral hygiene via suppressing oral microbes. In hospitalized patients, CHX mouthwash reduces the incidence of ventilator-associated pneumonia. However, CHX use was also associated with increased mortality, which might be related to nitrate-reducing bacteria. Currently, no study determines oral bacteria targeted by essential oils mouthwash in hospitalized patients using a metagenomic approach, which is the aim of this work. Paired analysis revealed eight bacterial genera (including Prevotella, Fusobacterium, and Selenomonas) with a decreased relative abundance, while Rothia increased after gargling the CHX mouthwash. After gargling Listerine, seven genera (including Parvimonas, Eubacterium, and Selenomonas) showed a decreased relative abundance, and the magnitudes were smaller compared to the CHX group. Fewer bacteria targeted by Listerine were reported to be nitrate-reducing compared to the CHX mouthwash. In conclusion, short-term gargling of the CHX mouthwash and Listerine altered oral microbiota in our hospitalized patients. The bacterial genera targeted by the CHX mouthwash and Listerine were largely different and the magnitudes of changes were smaller using Listerine. Functional alterations of gargling CHX and Listerine were also different. These findings can be considered for managing oral hygiene of hospitalized patients.