The Wen Group - Computational Biology of RNAs and Functional Genomics

We are a new computational biology lab of RNA and functional genomics at the Department of Genome Sciences, The John Curtin School of Medical Research (JCSMR), ANU.

Our group is devoted to exploring diverse modes of gene regulatory networks, both post-transcriptional gene regulation by small RNAs, structural RNAs, and RNA binding proteins, and transcriptional regulation by transcription factors. In early 1960, Jacob and Monod proposed the first gene regulatory model that genes can be regulated at both transcriptional and post-transcriptional levels. These regulatory elements have shown to regulate a majority of animal transcripts and exert profound control of development and physiology. Thus, their dysfunction has enormous implications in diverse human disease mechanisms. We are particular interested in understanding how these regulatory elements are made, how they evolve, how they regulate their target gene expression, and what biological impact they have on animal development and disease. We work on organisms ranging from insects to vertebrates.

As a computational Group, our research projects are typically multi-disciplinary. We employ a variety of computational approaches, integrating computational machine learning and statistical method development, high-throughput genome-wide data analysis, and molecular genetics/biochemistry experimental validations in collaboration.

We are currently recruiting PhD students as well as Honours students. There are various possible projects for students. As a multi-disciplinary research group, we are interested in students either with a good background in bioinformatics, computer science, statistics, engineering or a good background in molecular biology, biochemistry and some computational skills. If you would like to join, either to develop skills in computational biology or to tackle the proposed research questions, please email me at Jiayu.Wen@anu.edu.au.

Find more details here.

Current Research Projects

RNA-mediated gene regulation

  • Discovery of transcriptional active RNAs
  • Genome-wide investigation of RNA binding protein cooperation and competition
  • Discovery and characterization of functional long non-coding RNAs in diseases
  • Explorations of evolution and adaptive regulation by testis-specific hairpin RNA-target interaction networks across insect genomes (in collaboration with Prof. Eric Lai’s group at Sloan-Kettering Institute, New York)
  • Roles for RNA binding proteins in regulating alternative polyadenylation (APA) in the central nervous system
  • Roles for alternative polyadenylation (APA) in cardiac development (in collaboration with Prof. Thomas Preiss's group at JCSMR, ANU)

Transcriptional regulation - in collaboration with Dr. Qi Dai's Group at Stockholm University, Sweden

  • Gene regulation by cell-type specific transcription factor networks controlling neural cell fate specification
  • Neural cell-specific transcription factor networks regulate neural stem cell self-renewal and differentiation

Epigenetics regulation - in collaboration with Prof. Mattias Mannervik's Group at Stockholm University, Sweden

  • Investigation of the function of histone acetylation
  • Transcriptional coregulators modifying chromatin structures.

Single cell analysis in immunity - in collaboration with A/Prof Di Yu's Group at JCSMR, ANU

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Link to Google Scholar citations

  1. Lin CJ, Hu F, Dubruille R, Vedanayagam J, Wen J., Smibert P, Loppin B, Lai EC. The hpRNA/RNAi Pathway is essential to resolve intragenomic conflict in the Drosophila male germline. Developmental Cell, (2018). 46(3):316-326.e5. IF 9.6. Full Text HTML | PDF
  2. Jee D., Yang J., Park S., Farmer D., Wen J., Chou T., Chow A., Mcmanus M., Kharas M., and Lai EC. Dual strategies for Argonaute2 mediated biogenesis of erythroid miRNAs underlie conserved requirements for slicing in mammals. Molecular Cell, (2018). 69(2) 265-278.e6. IF 15.05. Full Text HTML | PDF
  3. Sanfilippo P., Wen J., and Lai EC. Landscape and evolution of tissue-specific alternative polyadenylation across Drosophila species. Genome Biology (2017). 18 (1), 229. IF 11.9. Full Text HTML | PDF
  4. Lin CJ, Wen J., Bejarano F, Hu F, Bortolamiol-Becet D1, Kan L, Sanfilippo P, Kondo S, Lai EC. Characterization of a TUTase/RNase complex required for Drosophila gametogenesis. RNA (2017). 23(3):284-296. IF 4.94 Full Text HTML | PDF
  5. Garaulet DL, Sun K., Li W., Wen J., Panzarino A.O Ńeil J. Hiesinger R.,Young M.,and Lai EC. miR-124 Regulates Diverse Aspects of Rhythmic Behavior in Drosophila. The Journal of Neuroscience, (2016). 36(12):3414-21. IF 7.36. (This paper was co-authored with the 2017 Nobel Prize Laureate in Physiology or Medicine Prof. Michael Young on circadian rhythm in Drosophila.). Full Text HTML | PDF
  6. Wen J., Duan H., Bejarano F., Okamura K., Lacramioara F., Julie B., Bortolamiol-Becet D., Martin R., Ruby JG and Lai EC. Adaptive regulation of testis gene expression and control of male fertility by the Drosophila hairpin RNA pathway. Molecular Cell, (2015) 57(1):165-78. IF 15.05. Full Text HTML | PDF
  7. Bortolamiol-Becet D., Hu F., Jee D., Wen J., Okamura K., Ching-Jung Lin, Stefan Ameres, and Lai EC. Selective suppression of the splicing-Mediated microRNA pathway by the terminal uridyltransferase Tailor. Molecular Cell. (2015). 59(2):217-28. IF 15.05. Full Text HTML | PDF
  8. Wen J., Leucci, E., Lund, A, Krogh A. and Parker BJ. Transcriptome dynamics of the microRNA inhibition response. Nucleic Acids Research, (2015). 43(13):6207-21. IF 9.1. Full Text HTML | PDF
  9. Wen J., Ladewig E., and Lai EC. Analysis of nearly one thousand mammalian mirtrons reveals novel features of Dicer substrates. PLOS Computational Biology, (2015). 11(9):e1004441. IF 5.28. Full Text HTML | PDF
  10. Wen J., Mohammed J, Tsai H, Robine N, Westholm JO, Ladewig E, Bortolamiol-Becet D, Dai Q, Okamura K, Flynt AS, Zhang D, Andrews J, Cherbas L, Kaufman TC, Cherbas P, Siepel A and Lai EC. Diversity of miRNAs, siRNAs and piRNAs across 25 Drosophila cell lines. Genome Research, (2014) 24(7), 1236-1250. IF 15.57. Full Text HTML | PDF
  11. Brown JB, Boley N, Eisman R, May GE, Stoiber MH, Duff MO, Booth BW, Wen J., Park S, Suzuki AM, Wan KH, Yu C, Zhang D, Carlson JW, Cherbas L, Eads BD, Miller D, Mockaitis K, Roberts J, Davis CA, Frise E, Hammonds AS, Olson S, Shenker S, Sturgill D, Samsonova AA, Weiszmann R, Robinson G, Hernandez J, Andrews J, Bickel PJ, Carninci P, Cherbas P, Gingeras TR, Hoskins RA, Kaufman TC, Lai EC, Oliver B, Perrimon N, Graveley BR, Celniker SE. Diversity and dynamics of the Drosophila transcriptome. Nature (2014) 512(7515), 393–399. IF 41.30. Full Text HTML | PDF
  12. The modENCODE Consortium. Gerstein MB, Rozowsky J, Yan KK, Wang D, Cheng C, Brown JB, Davis CA, Hillier L, Sisu C, Li JJ, Pei B, Harmanci AO, Duff MO, Djebali S, Alexander RP, Alver BH, Auerbach R, Bell K, Bickel PJ, Boeck ME, Boley NP, Booth BW, Cherbas L, Cherbas P, Di C, Dobin A, Drenkow J, Ewing B, Fang G, Fastuca M, Feingold EA, Frankish A, Gao G, Good PJ, Guigo R, Hammonds A, Harrow J, Hoskins RA, Howald C, Hu L, Huang H, Hubbard TJ, Huynh C, Jha S, Kasper D, Kato M, Kaufman TC, Kitchen RR, Ladewig E, Lagarde J, Lai E, Leng J, Lu Z, MacCoss M, May G, McWhirter R, Merrihew G, Miller DM, Mortazavi A, Murad R, Oliver B, Olson S, Park PJ, Pazin MJ, Perrimon N, Pervouchine D, Reinke V, Reymond A, Robinson G, Samsonova A, Saunders GI, Schlesinger F, Sethi A, Slack FJ, Spencer WC, Stoiber MH, Strasbourger P, Tanzer A, Thompson OA, Wan KH, Wang G, Wang H, Watkins KL, Wen J., Wen K, Xue C, Yang L, Yip K, Zaleski C, Zhang Y, Zheng H, Brenner SE, Graveley BR, Celniker SE, Gingeras TR, Waterston R. Comparative analysis of the transcriptome across distant species. Nature (2014) 512(7515):445-8. IF 41.30. Full Text HTML | PDF
  13. Frankel LB, Di Malta C., Wen J., Eskelinen E., Ballabio A. and Lund, AH. A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder. Nature Communication, (2014) 5:5840. current IF 11.47. Full Text HTML | PDF
  14. Simola DF, Wissler L, Donahue G, Waterhouse RM, Helmkampf M, Roux J, Nygaard S, Glastad KM, Hagen DE, Viljakainen L, Reese JT, Hunt BG, Graur D, Elhaik E, Kriventseva EV, Wen J., Parker BJ, Cash E, Privman E, Childers CP, Munoz-Torres MC, Boomsma JJ, Bornberg-Bauer E, Currie CR, Elsik CG, Suen G, Goodisman MA, Keller L, Liebig J, Rawls A, Reinberg D, Smith CD, Smith CR, Tsutsui N, Wurm Y, Zdobnov EM, Berger SL, Gadau J. Social insect genomes exhibit dramatic evolution in gene composition and regulation while preserving regulatory features linked to sociality. Genome Research. (2013) 23(8):1235-47. IF 15.57. Full Text HTML | PDF
  15. Stadthagen G, Tehler D, Hoyland-Kroghsbo NM, Wen J., Krogh A, Jensen KT, Santoni-Rugiu E, En-gelholm LH, Lund AH. Loss of miR-10a activates lpo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice. PLoS Genetics. (2013) 9(10):e1003913. IF 8.56. Full Text HTML | PDF
  16. Patella F., Leucci E., Evangelista M.,Parker BJ, Wen J., Mercatanti A., Lund A.,and Rainaldi G. MiR-492 impairs the angiogenic potential of endothelial cells. J Cell Mol Med, (2013) 17(8):1006- 15. IF 5.81. Full Text HTML | PDF
  17. Gregersen LH,Jacobsen A.,Frankel LB, Wen J., Krogh A.,and Lund AH. microRNA-143down-regulates Hexokinase 2 in colon cancer cells. BMC Cancer, (2012) 12:232. IF 3.77. Full Text HTML | PDF
  18. Wen J., Parker BJ., Jacobsen A., and Krogh A. MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action. RNA, (2011) 17(5):820-34. IF 4.94. Full Text HTML | PDF
  19. Parker BJ., Moltke I., RothA.,Washietl S., Wen J., Kellis M.,Breaker R.,and Pedersen JS. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes. Genome Research (2011) 21(11):1929-43. IF 15.57. Full Text HTML | PDF
  20. Lindblad-Toh K, Garber M, Zuk O, Lin MF, Parker BJ, Washietl S, Kheradpour P, Ernst J, Jordan G, Mauceli E, Ward LD, Lowe CB, Holloway AK, Clamp M, Gnerre S, Alfoldi J, Beal K, Chang J, Clawson H, Cuff J, Di Palma F, Fitzgerald S, Flicek P, Guttman M, Hubisz MJ, Jaffe DB, Jungreis I, Kent WJ, Kostka D, Lara M, Martins AL, Massingham T, Moltke I, Raney BJ, Rasmussen MD, Robinson J, Stark A, Vilella AJ, Wen J., Xie X, Zody MC; Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baldwin J, Bloom T, Chin CW, Heiman D, Nicol R, Nusbaum C, Young S, Wilkinson J, Worley KC, Kovar CL, Muzny DM, Gibbs RA; Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Cree A, Dihn HH, Fowler G, Jhangiani S, Joshi V, Lee S, Lewis LR, Nazareth LV, Okwuonu G, Santibanez J, Warren WC, Mardis ER, Weinstock GM, Wilson RK; Genome Institute at Washington University, Delehaunty K, Dooling D, Fronik C, Fulton L, Fulton B, Graves T, Minx P, Sodergren E, Birney E, Margulies EH, Herrero J, Green ED, Haussler D, Siepel A, Goldman N, Pollard KS, Pedersen JS, Lander ES, Kellis M. A high-resolution map of human evolutionary constraint using 29 mammals. Nature (2011) 478(7370):476-82. IF 41.30. Full Text HTML | PDF
  21. Frankel LB., Wen J., Lees M., Høyer-Hansen M., Farkas T., Krogh A., Jäättelä,M., Lund AH. microRNA-101 is a potent inhibitor of autophagy. The EMBO journal (2011) 30(22):4628-41. IF 9.84. Full Text HTML | PDF
  22. Chen Y., Jørgensen M., Kolde R., Zhao X., Parker BJ., Valen E., Wen J., Sandelin A., Prediction of RNA Polymerase II recruitment, elongation and stalling from histone modification data. BMC Genomics, (2011) 12:544. IF 4.36. Full Text HTML | PDF
  23. Jacobson A., Wen J., Marks DS., and Krogh A. Signatures of RNA binding proteins globally coupled to effective microRNA target sites. Genome Research (2010) 20(8):1010-9. IF 15.57. Full Text HTML | PDF
  24. Gregersen, LH, Jacobsen, A., Frankel, LB, Wen J., Krogh, A. and Lund, A. microRNA-145 targets YES and STAT1 in colon cancer cells. PLoS One, (2010) 5(1):e8836. IF 3.23. Full Text HTML | PDF
  25. Parker BJ.*, and Wen J. *, Predicting microRNA targets in time-series microarray experiments via functional data analysis. BMC Bioinformatics, (2009) 10:S32. (*equal first authors.) IF 3.45. Full Text HTML | PDF
  26. Wen J., FrickeyT., and WeillerGF. Computational prediction of candidate miRNAs and their targets from Medicago truncatula non-protein-coding transcripts. In Silico Biology, (2008) 8: 0024. Full Text HTML | PDF
  27. Wen J., Parker BJ., and Weiller GF. In silico identification and characterization of mRNA-like noncoding transcripts in Medicago truncatula. In Silico Biology, (2007) 7: 0034. Full Text HTML | PDF
  28. Steele EJ., Lindley RA., Wen J., and Weiller GF. Computational analyses how A-to-G mutations correlate with nascent mRNA hairpins at somatic hypermutation hotspots. DNA Repair (2006) 5(11):1346-63. IF 3.455. Full Text HTML | PDF