Nelson Lau

Our lab studies RNA interference (RNAi) mechanisms that protect genomes from the spread of transposable elements (TEs) and respond to viral RNA infections. Animal genomes are laden with TEs that draw their evolutionary roots from retroviruses that integrate into the host genome. Over millions of years of evolution, TEs have filled up over 45% of the human genome, yet the regulatory mechanisms of TE control are not fully understood. TE mobilization causes germ cell death, infertility, and genomic damage during cellular aging. Viruses are the modern form of this host genomic battle, and therefore animals use small regulatory RNAs and their associated PIWI and ARGONAUTE proteins to safeguard genomes from these invading genetic elements.

Mosquitoes are the major vector for pathogenic flaviviruses like Dengue, Zika, and West Nile viruses. Our Mosquito Small RNA Genomics pipeline, the MSRG database, tracks mosquito small RNAs are generated from viral mRNAs and TE RNAs, and many mosquitoes carry persistent Insect viruses that we are discovering in surveillance sampling of mosquitoes around the globe. We are testing the hypothesis that Mosquito Insect Viruses that are priming the RNAi pathway may temper the vectoring capacity of mosquitoes for pathogenic flaviviruses like Dengue, Zika and West Nile viruses. This work is conducted in close collaboration with colleagues at the BU National Emerging Infectious Diseases Laboratories (NEIDL).

Our lab also 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.

Selected Publications

1. Gamez S, Srivastav S, Akbari OS, Lau NC (2020). Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways. Cells. 2020 Sep 27; 9(10):2180. doi: 10.3390/cells9102180. PMCID: PMC7601171
2. 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. (2021). A mosquito small RNA genomics resource reveals dynamic evolution and host responses to viruses and transposons. Genome Research. 2021 Mar; 31(3):512-528. doi: 10.1101/gr.265157.120. Epub 2021 Jan 8. PMCID: PMC7919454
3. Henderson C, Brustolin M, Hegde S, Dayama G, Lau N, Hughes GL, Bergey C, Rasgon JL. Transcriptomic and small RNA response to Mayaro virus infection in Anopheles stephensi mosquitoes. PLoS Negl Trop Dis. 2022 Jun 28; 16(6):e0010507. doi: 10.1371/journal.pntd.0010507. eCollection 2022 Jun. PMID: 35763539. PMCID: PMC9273063
4. Feitosa-Suntheimer F, Zhu Z, Mameli E, Dayama G, Gold AS, Broos-Caldwell A, Troupin A, Rippee-Brooks M, Corley RB, Lau NC, Colpitts TM, Londoño-Renteria B. Dengue Virus-2 Infection Affects Fecundity and Elicits Specific Transcriptional Changes in the Ovaries of Aedes aegypti Mosquitoes. Front Microbiol. 2022 Jun 23; 13:886787. doi: 10.3389/fmicb.2022.886787. eCollection 2022. PMID: 35814655. PMCID: PMC9260120