1. MicroRNA biogenesis
miRNAs are a class of small RNAs around 22 nucleotides long that have emerged as critical regulators modulating almost all biological processes involving gene expression. MicroRNA genes are transcribed as long primary microRNAs (pri-miRNAs) and then processed by the Drosha–DGCR8 (DiGeorge syndrome critical region gene 8) complex into ~60-nt pre-miRNAs, which is the key step in miRNA biogenesis. How exactly the Drosha–DGCR8 complex recognizes pri-miRNAs and selects the processing site is not well understood. We have developed a new approach that we are currently using to study how the Drosha–DGCR8 complex chooses the processing site in human cells. Our previous studies suggested that the sequence of a given miRNA is not fixed, as annotated in the miRBase, but shows considerable variation at the ends. We are also assessing the functional significance of variant miRNA forms and the mechanism of their generation.
Taking advantage of our knowledge of miRNA biogenesis, which is the basis for how exogenously introduced siRNA/shRNA can work in mammalian cells, we are also interested in improving the design of siRNA/shRNA to increase potency and reduce side effects.
2. CRISPR-Cas9 system-based genome-wide functional screening in human cells
Taking advantage of the ease of knocking out target genes using the newly developed CRISPR-Cas9 genome-editing tool, we have independently developed an approach based on this system to perform genome-wide knockout screening in human cells. Currently we are using the method to study various biological processes, including virus replication.
Major Invited Speaker/Meeting Participant
2014 - "The Lower and Upper Stem–ssRNA Junctions Together Determine the Drosha Cleavage Site. RNA silencing" Keystone symposia (01/31/2014-02/05/2014), Seattle, US.
2014 - "Genome-Wide Functional Screening with the CRISPR-Cas9 System in Human Cells." GTC-None-coding RNAs and RNAi (06/19/2014-06/20/2014), San Diego, USA.
2015 - "A CRISPR-Cas9-Based Screen for Human Genes Essential for West Nile Virus-Induced Cell Death. Precision genome engineering and synthetic biology." Keystone symposia (01/11/2015-01/16/2015), Big Sky, USA.
- B.S., Fudan University, Shanghai, China (1989-1993)
- M.S., Fudan University, Shanghai, China (1993-1997)
- Ph.D., Fudan University, Shanghai, China (1997-2000)
Postdoctoral training, UCLA (2003-2005) and the Immune Disease Institute, Harvard Medical School (2005-2008)
View more of Dr. Wu's publications at Pubmed.