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RESEARCH

Research Summary

RNA plays a central role in the central dogma: 1) 70-90% of DNA could be transcribed into RNA, while only ~1.5% of RNA could be translated into proteins, suggesting the great potential of RNA as research targets (e.g. drug targets); 2) Even for the 1.5% protein-coding RNA, RNA levels only have around 40% explanatory power of protein abundance, suggesting post-transcription regulations such as RNA structure-based regulation. To date, there is growing interest in RNA studies (e.g. RNA vaccine), however, its clinical application has been greatly hindered by many technical limitations. My research interests are RNA-based technology development and applications. Below are some ongoing projects: 
1) Spatial RNA-seq has shown great potential to merge different information with tissue localization, but current approaches could only capture hundreds of genes per cell, limiting its application, hence we are developing the approach to capture more genes. 
2) Single-cell technologies have the advantages for cell heterogeneity and cell development trajectory studies. It has been shown lower expressed genes are more cell type-specific, especially for long non-coding RNAs (lincRNAs), however, low-expressed lincRNAs are difficult to capture at the single-cell level. Therefore, we are developing a single-cell- lincRNA sequencing approach. 
3) There is almost no difference in RNA expression between certain stages during early embryo development, but there are dramatic differences in the amounts of proteins. We aim to study the roles of RNA structure in post-transcriptional regulation of gene expression. 
4) RNA degrades easily, which poses a great challenge for RNA study. We are developing an approach to stabilize the RNA, even at a very low amount (single cell or 10pg). 
We are very interested in applying these approaches to different cellular developmental processes and diseases to better understand the roles of RNAs. 
 

Selected Publications

• Jiaxu Wang (co-first and co-corresponding author), Yu Zhang, Tong Zhang, Wen Ting Tan, Finnlay Lambert, Roland Huber, Shyam Prabhakar, Yue Wan; RNA structure profiling at single-cell resolution reveals new determinants of cell identity. (Nature Methods, 2024).
• Jiaxu Wang, Lin Yang, Anthony Cheng, Cheng-Yong Tham, Tan Wenting, Jefferson Darmawan, Paola Florez de Sessions, Yue Wan. Direct RNA sequencing coupled with adaptive sampling enriches RNAs of interest in the transcriptome. (Nature Communications, 2024)
• Jiaxu Wang; Tong Zhang; Yu Zhang; Wen Ting Tan; Ming Wen; Yang Shen; Finnlay R.P. Lambert; Roland G. Huber; Yue Wan; Genome-wide RNA structure changes during human neurogenesis modulate gene regulatory networks. (Molecular Cell, 2021)
• Yue, Zhao; Jiaxu Wang (co-first Author); Wai Nam, Liu; Shin Yie, Fong; Timothy Wai Ho, Shuen; Min, Liu; Sarah, Harden; Sue Yee, Tan; Jia Ying, Cheng; Wilson Wei Sheng, Tan; Jerry, Kok Yen Chan; Cheng Ean, Chee; Guan Huei, Lee; Han Chong, Toh; Seng Gee, Lim; Yue, Wan; Qingfeng, Chen; Analysis and validation of human targets and treatments using a hepatocellular carcinoma - immune humanized mouse model (Hepatology, 2021)
• Aw, Jong Ghut Ashley; Lim, Shaun W.; Jiaxu Wang (co-first Author); Lambert, Finnlay R.P.; Tan, Wen Ting; Shen, Yang; Zhang, Yu; Kaewsapsak, Pornchai; Li, Chenhao; Ng, Sarah B.; Vardy,Leah A.; Tan, Meng How; Nagarajan, Niranjan; Wan, Yue ; Determination of isoform-specific RNA structure with nanopore long reads. (Nature Biotechnology, 2020)
• Wang Jiaxu; Jenjaroenpun Piroon; Bhinge Akshay; Angarica Vladimir Espinosa; Del Sol Antonio; Nookaew Intawat; Kuznetsov Vladimir A; Stanton Lawrence W ; Single-cell gene expression analysis reveals regulators of distinct cell subpopulations among developing human neurons. (Genome Research, 2017)
• Wang Jiaxu; Qiao Mengran; He Qianqian; Shi Ronghua; Loh Sharon Jia Hui; Stanton Lawrence W; Wu Mian; Pluripotency Activity of Nanog Requires Biochemical Stabilization by Variant Histone Protein H2A.Z. (Stem Cells, 2015)
• Wang Jiaxu; He Qianqian; Han Chuanchun; Gu Hao; Jin Lei; Li Qun; Mei Yide; Wu Mian; p53-Facilitated miR-199a-3p Regulates Somatic Cell Reprogramming. (Stem Cells, 2012)