Our lab studies RNA interference (RNAi) mechanisms such as the PIWI/piRNA pathway which protects our genomes from the spread of transposable elements (TEs). Our DNA is inherently laden with TEs that have continued to infect our genomes. Over millions of years of evolution, TEs have filled up over 45% of our genome’s content. If TEs are unchecked, their mobilization causes germ cell death, infertility, and genomic damage during cellular aging. Therefore, our cells depend on small regulatory RNAs and their associated PIWI and ARGONAUTE proteins to safeguard genomes from these mobilizing elements.
Our lab applies functional and comparative genomics and biochemical approaches to dissect the molecular mechanisms for how PIWI / piRNA complexes silence genomic targets. By understanding the requirements and limitations of the PIWI/piRNA pathway, we may be able to uncover how TEs might evade suppression by these pathways to generate wide-spread TE landscape diversity across animal genomes. Our mechanistic studies will also help us find situations to enhance TE control and link TE mis-regulation to etiologies of genome decline. We are collaborating with several other groups at BUMC to look at the impact of TEs in skin cells, macrophages, and neurons. Towards this goal, we are exploring how loss of transposon silencing by RNAi pathways is tied to animal aging processes.
Recently, our lab has also extended our piRNA studies to mosquito cells and animals to examine how pathogenic flaviviruses like Dengue, Zika and West Nile viruses can generate small RNAs including viral piRNAs. We created and are continuing to update a Mosquito Small RNA Genomics pipeline, the MSRG database, to enable broad comparative analysis of mosquito small RNAs that may repress viral mRNAs and TE RNAs. Since many TEs are genomic relics and related to retroviruses, the RNAi pathway represents an adaptive immunity response to both evolutionary and on going infection threats in insects. This work is conducted in close collaboration with the BU National Emerging and Infectious Disease Laboratory (NEIDL).
Ma Q, Srivastav SP, Gamez S, Dayama G, Feitosa-Suntheimer F, Patterson EI, Johnson RM, Matson EM, Gold AS, Brackney DE, Connor JH, Colpitts TM, Hughes GL, Rasgon JL, Nolan T, Akbari OS, Lau NC. A mosquito small RNA genomics resource reveals dynamic evolution and host responses to viruses and transposons. Genome Res. 2021 Jan 08.PMID:33419731
Gamez S, Srivastav S, Akbari OS, Lau NC. Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways. Cells. 2020 09 27; 9(10). PMID:32992598
Srivastav SP, Rahman R, Ma Q, Pierre J, Bandyopadhyay S, Lau NC (2019). Har-P, a short P-element variant, weaponizes P-transposase to severely impair Drosophila development. eLife 2019;8:e49948. PMID: 31845649
Zeldich E, Chen CD, Boden E, Howat B, Nasse JS, Zeldich D, Lambert AG, Yuste A, Cherry JD, Mathias RM, Ma Q, Lau NC, McKee AC, Hatzipetros T, Abraham CR. Klotho Is Neuroprotective in the Superoxide Dismutase (SOD1G93A) Mouse Model of ALS. J Mol Neurosci. 2019 Oct; 69(2):264-285. PMID: 31250273
Gushchanskaia ES, Esse R, Ma Q, Lau NC, Grishok A. Interplay between small RNA pathways shapes chromatin landscapes in C. elegans. Nucleic Acids Res. 2019 06 20; 47(11):5603-5616. PMID: 31216042
Kozeretska IA, Shulha VI, Serga SV, Rozhok AI, Protsenko OV, Lau NC (2018). A rapid change in P-element-induced hybrid dysgenesis status in Ukrainian populations of Drosophila melanogaster. Biol Lett. 2018 08; 14(8). PMID: 30135116
Clark JP, Rahman R, Yang N, Yang LH, Lau NC. (2017) Drosophila PAF1 Modulates PIWI/piRNA Silencing Capacity. Curr Biol. 2017 Sep 11;27(17):2718-2726.e4. doi: 10.1016/j.cub.2017.07.052. Epub 2017 Aug 24.
Toombs, T., Sytnikova, Y., Ang, I., Chirn, GW, Lau, NC*, Blower, MD*. (2017) Xenopus Piwi proteins interact with a broad proportion of the oocyte transcriptome. RNA. Apr;23(4):504-520. doi: 10.1261/rna.058859.116. Epub 2016 Dec 28. *Co-corresponding Author.
Madison-Villar,M., Sun, C., Lau, NC, Settles,M., Mueller, RL. Small RNAs from a big genome: the piRNA pathway and transposable elements in the salamander species Desmognathus fuscus. (2016). J Mol Evol. Oct;83(3-4):126-136. Epub 2016 Oct 14.
Rahman, R., Chirn, GW, Kanodia, A, Sytnikova, Y., Brembs, B, Bergman, CM, Lau, NC. (2015) Unique transposon landscapes are pervasive across Drosophila melanogaster genomes. Nucleic Acids Research. Dec 15;43(22):10655-72. doi: 10.1093/nar/gkv1193. PMCID: PMC4678822.
Chirn,GW, Rahman, R, Sytnikova, YA, Matts, JA, Zeng, M, Gerlach, D, Yu, M, Berger, B, Kile, BT, and Lau, NC. (2015) Conserved piRNA expression from a distinct set of piRNA cluster loci in Eutherian mammals. Plos Genetics 11 (11): e1005652. doi:10.1371/ journal.pgen.1005652. PMCID: PMC4654475.
Sytnikova, Y., Rahman, R., Chirn, G.W., Post, C., Clark, J., and Lau, N.C. (2014). Transposable element dynamics and PIWI regulation impacts lncRNA and gene expression diversity in Drosophila ovarian cell cultures. Genome Research. 2014 Dec;24(12):1977-90. PMID: 25267525. PMCID: PMC4248314
Post, C, Clark, J, Sytnikova, Y., Chirn, G.W., and Lau, N.C. (2014). The capacity of target silencing by the Drosophila Piwi protein and piRNAs. RNA. 2014 Dec;20(12):1977-86. PMID: 25336588. PMCID: PMC4238361.
