Nelson Lau

Associate Professor, Biochemistry Director, Genome Science Institute

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.

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).

Selected Publications

  1. Srivastav SP, Rahman R, Ma Q, Pierre J, Bandyopadhyay S, Lau NC. Har-P, a short P-element variant, weaponizes P-transposase to severely impair Drosophila development. eLife 2019;8:e49948. PMID: 31845649 
  2. 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
  3. 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