An Lab Homepage

[2024] Jeniffer Atim joins TeamLINE1. Welcome!

[2024] Kick off the New Year with a bioRxiv preprint from TeamLINE1: "YY1 is a transcriptional activator of mouse LINE-1 Tf subfamily!"

[2023] Dr. An receives a pilot grant from Sanford Research.

[2023] Heather Collazo joins TeamLINE1. Welcome!

[2022] Grace Nielsen receives the Joseph F. Nelson Summer Research Scholarship.

[2022] Jada Tschetter receives the Schultz-Werth Award.

[2022] Jacob Devine is accepted into University of South Dakota MD Program.

[2021] Lisa Wipf is featured by "news@SDState". Good job, Lisa!

[2021] First bioRxiv preprint from TeamLINE1: "Subfamily-specific differential contribution of individual monomers and the tether sequence to mouse L1 promoter activity"!

[2021] Raj Naldini joins TeamLINE1. Welcome!

[2021] Dr. An receives SDSU F. O. Butler Award for Excellence in Research.

[2020] Karabi Saha joins our Ph.D. program. Welcome!

[2020] Lingqi Kong passes his Ph.D. final oral exam. Congrats!

[2020] Partha Saha passes his Ph.D. final oral exam. Congrats!

[2019] Dr. An receives an R03 grant from NICHD.

[2019] Both Mason and Chase are accepted into University of South Dakota M.D. Program.

[2019] Heather Collazo joins us this summer as a fellow of the FAST REEU program.

[2019] Trenton LaCanne receives the Joseph F. Nelson Summer Research Scholarship.

[2019] Read our review "Recently mobilized transposons in the human genome" and collaborative work "Transposon expression and repression in human fetal germ cells".

[2018] Dr. An receives an R15 AREA grant from NIGMS.

[2018] Chase Habben receives the Schultz-Werth Paper Award.

[2018] Partha Saha receives Sigma Xi Graduate Proposal Competition 2nd Place.

[2018] Simon Newkirk receives Professional Staff Excellence in Scholarly Activity Award.

[2017] Chase Habben receives the Joseph F. Nelson Summer Research Scholarship.

[2017] Mason Jones receives the Schultz-Werth Paper Award.

[2017] Simon's PNAS paper is out. See Commentary by J.P. Wang and Highlight by C. Chen.

[2016] Mason Jones receives the Joseph F. Nelson Summer Research Scholarship.

[2016] Nicole Vanden Berg is accepted into University of Minnesota VetMed Program.

[2016] Dr. An is named the College of Pharmacy Outstanding Researcher.

[2015] Dr. An receives two R21 grants from NICHD and NIH Office of the Director.

[2015] Our Genome Research paper is now online.

[2014] We are now a member of NIGMS P50 Center for Systems Biology of Retrotransposition.

What is LINE-1 or L1? Long interspersed elements (LINEs) are common components of mammalian genomes. The human genome contains over 500,000 LINE-1 (L1) copies, most of which are 5' truncated. It is estimated that up to 100 L1s are active in the average diploid human genome, whereas ~3000 are potentially active in a diploid mouse genome. Go to Recommended Readings to learn more about these fascinating elements.

Genetic and Epigenetic Regulation of LINE-1 Retrotransposons

L1 replicates exclusively inside individual cells, involving steps such as transcription, translation, target-primed reverse transcription and integration. Using mammalian cell culture and transgenic mouse as primary systems, we are interested in dissecting mechanisms of L1 retrotransposition, especially host factors involved in genetic and epigenetic regulation of L1 activity and evolutionary dynamics.

Functional Impacts of LINE-1 retrotransposons

L1 is the only active autonomous transposable element in the human genome and it has been replicating in mammals since before the mammalian radiation. We are interested in developing novel mouse models and using them to investigate the impacts of L1 retrotransposition on genomic structure and function. We are particularly interested in the timing of L1 retrotransposition and the corresponding mutational burden during animal development and cancer progression.

1. Saha K., Nielsen G.I., Nandani R., Zhang Y., Kong L., Ye P., An W. YY1 is a transcriptional activator of the mouse LINE-1 Tf subfamily. Nucleic Acids Res. 2024 Oct 26:gkae949. Online ahead of print. PMID: 39460630. DOI: 10.1093/nar/gkae949. Posted January 4, 2024 on bioRxiv (initial version)
2. Kong L., Saha S., Hu Y., Tschetter J.N., Habben C.E., Whitmore L.S., Yao C., Ge X., Ye P., Newkirk S.J., An W. Subfamily-specific differential contribution of individual monomers and the tether sequence to mouse L1 promoter activity. Mobile DNA, 13 (2022). PMID: 35443687. PMCID: PMC9022269. DOI: 10.1186/s13100-022-00269-z. Posted December 4, 2021 on bioRxiv (initial version)
3. Gu Z., Liu Y., Zhang Y., Cao H., Lyu J., Wang X., Wylie A., Newkirk S.J., Jones A.E., Lee M. Jr., Botten G.A., Deng M., Dickerson K.E., Zhang C.C., An W., Abrams J.M. and Xu J. Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia. Nature Genetics, 53:672–682 (2021). PMID: 33833453. PMCID: PMC8270111. DOI: 10.1038/s41588-021-00829-8
4. Newkirk S.J., Kong L., Jones M.M., Habben C.E., Dilts V.L., Ye P. and An W. Subfamily-specific quantification of endogenous L1 retrotransposons by droplet digital PCR. Analytical Biochemistry, 601:113779 (2020). PMID: 32442414. PMCID: PMC7714369. DOI: 10.1016/j.ab.2020.113779
5. Liu R., Sreenivasan C., Yu H., Sheng Z., Newkirk S.J., An W., Smith D.F., Chen X., Wang D. and Li F. Influenza D virus diverges from its related influenza C virus in the recognition of 9-O-acetylated N-acetyl- or N-glycolyl-neuraminic acid-containing glycan receptors. Virology, 545:16-23 (2020). PMID: 32174455. PMCID: PMC7174096. DOI: 10.1016/j.virol.2020.02.007
6. Newkirk S.J. and An W. UHRF1: a jack of all trades, and a master epigenetic regulator during spermatogenesis. Biology of Reproduction, 102:1147-1152 (2020). PMID: 32101289. PMCID: PMC7253785. DOI: 10.1093/biolre/ioaa026
7. Ray D.A., Paulat N., An W., Boissinot S., Cordaux R., Kaul T., Freeman B. and Belancio V. The 2019 FASEB Science Research Conference on The Mobile DNA Conference: 25 Years of Discussion and Research, June 23–28, Palm Springs, California, USA. FASEB Journal, 33(11):11625-11628 (2019). PMID: 31671501. DOI: 10.1096/fj.201902390
8. Vazquez B.N., Thackray J.K., Simonet N., Chahar S., Kane-Goldsmith N., Newkirk S.J., Lee S., Xing J., Verzi M.P., An W., Vaquero A., Tischfield J.A. and Serrano L. SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina. Nucleic Acids Research, 47:7870–7885 (2019). PMID: 31226208. PMCID: PMC6735864. DOI: 10.1093/nar/gkz519
9. Wang Z., McSwiggin H., Newkirk S.J., Wang Y., Oliver D., Tang C., Lee S., Wang S., Yuan S., Zheng H., Ye P., An W. and Yan W. Insertion of a chimeric retrotransposon sequence in mouse Axin1 locus causes metastable kinky tail phenotype. Mobile DNA, 10:17 (2019). PMID: 31073336. PMCID: PMC6500023. DOI: 10.1186/s13100-019-0162-7
10. Saha P. and An W. Recently Mobilized Transposons in the Human Genome. In: Encyclopedia of Life Sciences. John Wiley & Sons Ltd, Chichester. (2019). DOI: 10.1002/9780470015902.a0020837
11. Reznik B., Cincotta S.A., Jaszczak R.G., Mateo L.J., Shen J., Cao M., Baskin L., Ye P., An W. and Laird D.J. Heterogeneity of transposon expression and activation of the repressive network in human fetal germ cells. Development 146(12):dev171157 (2019). PMID: 30658985. PMCID: PMC6602354 . DOI: 10.1242/dev.171157
12. Kawano K., Doucet A.J., Ueno M., Kariya R., An W., Marzetta F., Kuroki M., Turelli P., Sukegawa S., Okada S., Strebel K., Trono D. and Ariumi Y. HIV-1 Vpr and p21 restrict LINE-1 mobility. Nucleic Acids Research 46:8454–8470 (2018). PMID: 30085096. PMCID: PMC6144823. DOI: 10.1093/nar/gky688
13. Sheng Z., Liu R., Yu J., Ran Z., Newkirk S.J., An W., Li F. and Wang D. Identification and characterization of viral defective RNA genomes in influenza B virus. Journal of General Virology 99(4):475-488 (2018). PMID: 29458654. PMCID: PMC5982128. DOI: 10.1099/jgv.0.001018
14. Newkirk S.J., Lee S., Grandi F.C., Gaysinskaya V., Rosser J.M., Vanden Berg N., Hogarth C.A., Marchetto MCN, Muotri A.R., Griswold M.D., Ye P., Bortvin A., Gage F.H., Boeke J.D. and An W. Intact piRNA pathway prevents L1 mobilization in male meiosis. Proceedings of the National Academy of Sciences of the United States of America 114:E5635–E5644 (2017). PMID: 28630288. PMCID: PMC5514719. DOI: 10.1073/pnas.1701069114. Commented by: Wang P.J. Tracking LINE1 retrotransposition in the germline. Proceedings of the National Academy of Sciences of the United States of America 114:7194–7196 (2017). Highlighted by: Chen C. A novel reporter mouse to monitor in vivo retrotransposition in the germline. Biology of Reproduction 97:335-336 (2017)
15. Kannan M., Li J., Fritz S.E., Husarek K.E., Sanford J.C., Sullivan T.L., Tiwary P.K., An W., Boeke J.D. and Symer EE. Dynamic silencing of somatic L1 retrotransposon insertions reflects the developmental and cellular contexts of their genomic integration. Mobile DNA 8:8 (2017). PMID: 28491150. PMCID: PMC5424313. DOI: 10.1186/s13100-017-0091-2.
16. Newkirk S.J. and An W. L1 Regulation in Mouse and Human Germ Cells. in Human Retrotransposons in Health and Disease, ed Cristofari G (Springer International Publishing), pp 29-61 (2017). DOI: 10.1007/978-3-319-48344-3_2. (PDF available)
17. Kharytonchyk S., King S.R., Ndongmo C.B., Stilger K.L., An W. and Telesnitsky A. Resolution of Specific Nucleotide Mismatches by Wild-Type and AZT-Resistant Reverse Transcriptases during HIV-1 Replication. Journal of Molecular Biology. 428:2275–2288 (2016). PMID: 27075671. PMCID: PMC4884515. DOI: 10.1016/j.jmb.2016.04.005.
18. Grandi F.C., Rosser J.M., Newkirk S.J., Yin J., Jiang X., Xing Z., Whitmore L., Bashir S., Ivics Z., Izsvák Z., Ye P., Yu Y.E. and An W. Retrotransposition creates sloping shores: a graded influence of hypomethylated CpG islands on flanking CpG sites. Genome Research. 25:1135-1146 (2015). PMID: 25995269. PMCID: PMC4509998. DOI: 10.1101/gr.185132.114.
19. Grandi F.C. and An W. Non-LTR retrotransposons and microsatellites: Partners in genomic variation. Mobile Genetic Elements. 3:e25674 (2013). PMID: 24195012. PMCID: PMC3812793. DOI: 10.4161/mge.25674.
20. O'Donnell K.A., An W., Schrum C.T., Wheelan S.J. and Boeke J.D. Controlled insertional mutagenesis using a LINE-1 (ORFeus) gene-trap mouse model. Proceedings of the National Academy of Sciences of the United States of America 110:E2706-13 (2013). PMID: 23818630. PMCID: PMC3718180. DOI: 10.1073/pnas.1302504110.
21. Xie Y., Mates L., Ivics Z., Izsvák Z., Martin S.L. and An W. Cell division promotes efficient retrotransposition in a stable L1 reporter cell line. Mobile DNA. 4:10 (2013). PMID: 23497436. PMCID: PMC3607998. DOI: 10.1186/1759-8753-4-10.
22. Grandi F.C., Rosser J.M. and An W. LINE-1 derived poly(A) microsatellites undergo rapid shortening and create somatic and germline mosaicism in mice. Molecular Biology and Evolution. 30:503-12 (2013). PMID: 23125228. PMCID: PMC3563966. DOI: 10.1093/molbev/mss251.
23. Ray D., Hogarth C.A., Evans E.B., An W., Griswold M.D. and Ye P. Experimental validation of Ankrd17 and Anapc10, two novel meiotic genes predicted by computational models in mice. Biology of Reproduction 86(4):102 (2012). PMID: 22190705. PMCID: PMC4480071. DOI: 10.1095/biolreprod.111.095216.
24. Rosser J.M. and An W. L1 expression and regulation in humans and rodents. Frontiers in Bioscience E4:2203-25 (2012). PMID: 22202032. PMCID: PMC4457320. 
25. An W., Dai L., Niewiadomska A.M., Yetil A., O'Donnell K.A., Han J.S. and Boeke J.D. Characterization of a synthetic human LINE-1 retrotransposon ORFeus-Hs. Mobile DNA. 2:2 (2011). PMID: 21320307. PMCID: PMC3045867. DOI: 10.1186/1759-8753-2-2.
26. Xie Y., Rosser J.M., Thompson T.L., Boeke J.D. and An W. Characterization of L1 retrotransposition with high-throughput dual-luciferase assays. Nucleic Acids Research 39, e16 (2011). PMID: 21320307. PMCID: PMC3045867. DOI: 10.1093/nar/gkq1076.
27. Rosser J.M. and An W. Repeat-induced gene silencing of L1 transgenes is correlated with differential promoter methylation. Gene 456, 15-23 (2010). PMID: 20167267. PMCID: PMC3001326. DOI: 10.1016/j.gene.2010.02.005.
28. An W., Davis E.S., Thompson T.L., O'Donnell K.A., Lee C-Y and Boeke J.D. Plug and play modular strategies for synthetic retrotransposons. Methods 49, 227-35 (2009). PMID: 19481606. PMCID: PMC2763960. DOI: 10.1016/j.ymeth.2009.05.013.
29. Han Y., Lin Y.B., An W., Xu J., Yang H.C., O'Connell K., Dordai D., Boeke J.D., Siliciano J.D. and Siliciano RF. Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough. Cell Host Microbe 4, 134-46 (2008). PMID: 18692773. PMCID: PMC2604135. DOI: 10.1016/j.chom.2008.06.008.
30. An W., Han J.S., Schrum C.M., Maitra A., Koentgen F. and Boeke J.D. Conditional activation of a single-copy L1 transgene in mice by Cre. Genesis 46, 373-83 (2008). PMID: 18615728. PMCID: PMC2614868. DOI: 10.1002/dvg.20407.
31. Boeke J.D., An W., Dai L., Davis E.S., Han, J.S., O'Donnell K.A., Scheifele L.Z. and Wheelan, S.J. Retrotransposons-natural and synthetic. in Retrotransposition, Diversity and the Brain (eds. Gage, F.H. & Christen, Y.) 21-32 (Springer, 2008). doi:10.1007/978-3-540-74966-0_3. ISBN: 978-3-540-74965-3 (Print) 978-3-540-74966-0 (Online)
32. An W., Han J.S., Wheelan S.J., Davis E.S., Coombes C.E., Ye P., Triplett C. and Boeke J.D. Active retrotransposition by a synthetic L1 element in mice. Proceedings of the National Academy of Sciences of the United States of America 103, 18662-7 (2006). PMID: 17124176. PMCID: PMC1693719. DOI: 10.1073/pnas.0605300103.
33. An W. and Boeke J.D. Transposon technology and vertebrate functional genomics. Genome Biology 6, 361 (2005). PMID: 16356279. PMCID: PMC1414074. DOI: 10.1186/gb-2005-6-12-361.

Undergraduate Student

Projects are available for motivated undergraduate students. Will work on independent projects as well as teaming with experienced graduate students and postdocs. Must be committed and have a passion for biomedical research.

Graduate Student

No current openings. Prospective students may submit pre-application inquiry to Dr. An.
Ph.D. Program and Instructions

1. Moran J.V., Holmes S.E., Naas T.P., DeBerardinis R.J., Boeke J.D. and Kazazian H.H., Jr. High frequency retrotransposition in cultured mammalian cells. Cell 87, 917-927 (1996). PMID: 8945518. First demonstration of L1 retrotransposition in cell culture
2. Szak S.T., Pickeral O.K., Makalowski W., Boguski M.S., Landsman D. and Boeke J.D. Molecular archeology of L1 insertions in the human genome. Genome Biology 3, research0052 (2002). PMID: 12372140. Detailed account of L1 characteristics in our genome
3. Han J.S. and Boeke J.D. A highly active synthetic mammalian retrotransposon. Nature 429, 314-318. (2004) PMID: 15152256. The genesis of a synthetic L1, later known as ORFeus
4. Hancks D.C., Kazazian H.H. Jr. Active human retrotransposons: variation and disease. Current Opinion in Genetics and Development. 22(3):191-203 (2012).PMID: 22406018. A comprehensive catalog of sporadic diseases caused by human retrotransposons
5. Rosser, J.M. and An, W. L1 expression and regulation in humans and rodents. Frontiers in Bioscience E4:2203-25 (2012). PMID: 22202032. Our own review on L1 expression and regulation. 
6. Bao J., Yan W. Male germline control of transposable elements. Biology of Reproduction 86(5):162, 1-14 (2012). PMID: 22357546. A recent review of retrotransposon regulation in the male germ line
7. Sedivy J.M., Kreiling J.A., Neretti N., De Cecco M., Criscione S.W., Hofmann J.W., Zhao X., Ito T., Peterson A.L. Death by transposition - the enemy within? Bio essays. 35(12):1035-43 (2013). PMID: 24129940. A recent review of the role of retrotransposition in cellular senescence and aging
8. Carreira P.E., Richardson S.R., Faulkner G.J. L1 retrotransposons, cancer stem cells and oncogenesis. FEBS J. 281(1):63-73 (2014). PMID: 24286172. A recent review of the role of retrotransposition in oncogenesis
9. Volkman H.E., Stetson D.B. The enemy within: endogenous retroelements and autoimmune disease. Nature Immunology 15(5):415-22 (2014). PMID: 24747712. A recent review of the role of retrotransposition in autoimmune diseases
10. Erwin JA, Marchetto MC, Gage FH. Mobile DNA elements in the generation of diversity and complexity in the brain. Nature Reviews Neurosciences 15(8):497-506 (2014). PMID: 25005482. A recent review of the role of retrotransposition during neurogenesis and in neurological disorders

And, of course, many more can be found by a PubMed Search.