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8. Diversity in immunogenomics: the value and the challenge

Author

Peng, Kerui, Safonova, Yana, Shugay, Mikhail, Popejoy, Alice, Rodriguez, Oscar, Breden, Felix, Brodin, Petter, Burkhardt, Amanda M., Bustamante, Carlos, Cao-Lormeau, Van-Mai, Corcoran, Martin M., Duffy, Darragh, Guajardo, Macarena Fuentes, Fujita, Ricardo, Greiff, Victor, Jonsson, Vanessa D., Liu, Xiao, Quintana-Murci, Lluis, Rossetti, Maura, Xie, Jianming, Yaari, Gur, Zhang, Wei, Abedalthagafi, Malak S., Adekoya, Khalid O., Ahmed, Rahaman A., Chang, Wei-Chiao, Gray, Clive, Nakamura, Yusuke, Lees, William D., Khatri, Purvesh, Alachkar, Houda, Scheepers, Cathrine, Watson, Corey T., Hedestam, Gunilla B. Karlsson, and Mangul, Serghei

Subjects
Quantitative Biology - Genomics
Abstract

With the advent of high-throughput sequencing technologies, the fields of immunogenomics and adaptive immune receptor repertoire research are facing both opportunities and challenges. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become an increasingly important tool to characterize T and B cell responses in settings of interest. However, the majority of AIRR-seq studies conducted so far were performed in individuals of European ancestry, restricting the ability to identify variation in human adaptive immune responses across populations and limiting their applications. As AIRR-seq studies depend on the ability to assign VDJ sequence reads to the correct germline gene segments, efforts to characterize the genomic loci that encode adaptive immune receptor genes in different populations are urgently needed. The availability of comprehensive germline gene databases and further applications of AIRR-seq studies to individuals of non-European ancestry will substantially enhance our understanding of human adaptive immune responses, promote the development of effective diagnostics and treatments, and eventually advance precision medicine., Comment: 22 pages,1 table

Published
2020

10. Diversity in immunogenomics: the value and the challenge.

Author

Peng, Kerui, Safonova, Yana, Shugay, Mikhail, Popejoy, Alice, Rodriguez, Oscar, Breden, Felix, Brodin, Petter, Burkhardt, Amanda, Bustamante, Carlos, Cao-Lormeau, Van-Mai, Corcoran, Martin, Duffy, Darragh, Fuentes-Guajardo, Macarena, Fujita, Ricardo, Greiff, Victor, Jönsson, Vanessa, Liu, Xiao, Quintana-Murci, Lluis, Rossetti, Maura, Xie, Jianming, Yaari, Gur, Zhang, Wei, Abedalthagafi, Malak, Adekoya, Khalid, Ahmed, Rahaman, Chang, Wei-Chiao, Gray, Clive, Nakamura, Yusuke, Lees, William, Khatri, Purvesh, Alachkar, Houda, Scheepers, Cathrine, Watson, Corey, Karlsson Hedestam, Gunilla, and Mangul, Serghei

Subjects
B-Lymphocytes, Databases, Genetic, Genomics, Germ Cells, Humans, Immunogenetics, Receptors, Antigen, B-Cell, Receptors, Antigen, T-Cell, T-Lymphocytes, Whole Genome Sequencing
Abstract

Immunogenomics studies have been largely limited to individuals of European ancestry, restricting the ability to identify variation in human adaptive immune responses across populations. Inclusion of a greater diversity of individuals in immunogenomics studies will substantially enhance our understanding of human immunology.

Published
2021

11. MiR-22 as a metabolic silencer and liver tumor suppressor.

Author

Wang, Lijun, Wang, Yu-Shiuan, Mugiyanto, Eko, Chang, Wei-Chiao, and Yvonne Wan, Yu-Jui

Subjects
Cancer, Hepatitis, Liver, Metabolism, MicroRNA-22(miR-22), Non-alcoholic steatohepatitis, Steatosis
Abstract

With obesity rate consistently increasing, a strong relationship between obesity and fatty liver disease has been discovered. More than 90% of bariatric surgery patients also have non-alcoholic fatty liver diseases (NAFLDs). NAFLD and non-alcoholic steatohepatitis (NASH), which are the hepatic manifestations of metabolic syndrome, can lead to liver carcinogenesis. Unfortunately, there is no effective medicine that can be used to treat NASH or liver cancer. Thus, it is critically important to understand the mechanism underlying the development of these diseases. Extensive evidence suggests that microRNA 22 (miR-22) can be a diagnostic marker for liver diseases as well as a treatment target. This review paper focuses on the roles of miR-22 in metabolism, steatosis, and liver carcinogenesis. Literature search is limited based on the publications included in the PubMed database in the recent 10 years.

Published
2020

13. Functional Effects of let-7g Expression in Colon Cancer Metastasis.

Author

Chang, Che-Mai, Wong, Henry Sung-Ching, Huang, Chien-Yu, Hsu, Wen-Li, Maio, Zhi-Feng, Chiu, Siou-Jin, Tsai, Yao-Ting, Chen, Ben-Kuen, Wan, Yu-Jui Yvonne, Wang, Jaw-Yuan, and Chang, Wei-Chiao

Subjects
colorectal cancer, let-7g, microRNA, the cancer genome atlas (TCGA), store-operated calcium, the cancer genome atlas, store-operated calcium, Oncology and Carcinogenesis
Abstract

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment.

Published
2019

14. Development of an enrichment-free one-pot sample preparation and ultra-high performance liquid chromatography-tandem mass spectrometry method to identify Immunoglobulin A1 hinge region O-glycoforms for Immunoglobulin A nephropathy

Author

Chen, Hsiao-Fan, Kao, Chih-Chin, Ka, Shuk-Man, Wang, San-Yuan, Chen, Michael X., Chen, Guan-Yuan, Weng, Te-I, Lai, Ruo-Yun, Yeh, Shu-Ching, Lin, Yen-Chung, Chen, Hsi-Hsien, Chang, Wei-Chiao, Wu, Mai-Szu, and Tsai, I-Lin

Published
2022
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33. SIGLEC-3 (CD33) serves as an immune checkpoint receptor for HBV infection

Author

Tsai, Tsung-Yu, Huang, Ming-Ting, Sung, Pei-Shan, Peng, Cheng-Yuan, Tao, Mi-Hua, Yang, Hwai-I, Chang, Wei-Chiao, Yang, An-Suei, Yu, Chung-Ming, Lin, Ya-Ping, Bau, Ching-Yu, Huang, Chih-Jen, Pan, Mei-Hung, Wu, Chung-Yi, Hsiao, Chwan-Deng, Yeh, Yi-Hung, Duan, Shiteng, Paulson, James C., and Hsieh, Shie-Liang

Subjects
Prevention, Complications and side effects, Physiological aspects, Development and progression, Risk factors, Health aspects, Hepatitis B surface antigen -- Physiological aspects -- Health aspects, Lectins -- Physiological aspects -- Health aspects, Hepatocellular carcinoma -- Risk factors -- Prevention, Hepatitis B -- Complications and side effects -- Development and progression, Membrane proteins -- Physiological aspects -- Health aspects, Hepatitis associated antigen -- Physiological aspects -- Health aspects, Hepatoma -- Risk factors -- Prevention
Abstract

Introduction HBV infection is a worldwide health problem, and chronic HBV infection frequently results in liver cirrhosis and hepatocellular carcinoma (HCC). In HBV-infected hepatocytes, viral DNA enters the nucleus and [...], Chronic hepatitis B (CHB) infection is rarely eradicated by current antiviral nucleos(t)ide analogues. We found that [alpha]2,6-biantennary sialoglycans of HBV surface antigen (HBsAg) bound human SIGLEC-3 (CD33) by IP and ELISA, and the binding affinity between SIGLEC-3 and [alpha]2,6-biantennary sialoglycans was determined by biolayer interferometry (equilibrium dissociation constant [KD]: 1.95 * [10.sup.-10] [+ or -] 0.21 * [10.sup.-10] M). Moreover, HBV activated SIGLEC-3 on myeloid cells and induced immunosuppression by stimulating immunoreceptor tyrosine-based inhibitory motif phosphorylation and SHP-1/-2 recruitment via [alpha]2,6-biantennary sialoglycans on HBsAg. An antagonistic anti-SIGLEC-3 mAb reversed this effect and enhanced cytokine production in response to TLR-7 agonist GS-9620 in PBMCs from CHB patients. Moreover, anti-SIGLEC-3 mAb alone was able to upregulate the expression of molecules involved in antigen presentation, such as CD80, CD86, CD40, MHC-I, MHC-II, and PD-L1 in [CD14.sup.+] cells. Furthermore, SIGLEC-3 SNP rs12459419 C, which expressed a higher amount of SIGLEC-3, was associated with increased risk of hepatocellular carcinoma (HCC) in CHB patients (HR: 1.256, 95% CI: 1.027-1.535, P = 0.0266). Thus, blockade of SIGLEC-3 is a promising strategy to reactivate host immunity to HBV and lower the incidence of HCC in the CHB patient population.

Published
2021
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