Area: Molecular and Cellular Biology
Dr. Li received the award for his concentrated his research on the design and application of bioinformatics algorithms to elucidate global epigenetic mechanisms in development and diseases such as cancer. Epigenetics is the study of modifications in gene activity that are not dependent on the underlying DNA sequence, including histone medications, alternative polyadenylation and DNA methylation. Dr. Li has developed a series of widely used bioinformatics algorithms for epigenetic sequencing data analysis. In close collaboration with experimental biologists, he has used big data bioinformatics analysis to gain novel biological insights in stem cells, aging and cancers.
In a Nature Genetics paper, Dr. Li discovered the first epigenetic signature for tumor suppressors in normal cells, through integrative analysis of more than 1,100 genome-wide epigenetic profiles, mutations from over 8,200 tumor-normal pairs and experimental data from clinical samples. A subsequent paper described the development of a novel bioinformatics solution called DaPars for Dynamic Analyses of Alternative Polyadenylation directly from RNA-Seq. In collaboration with the Wagner lab at University of Texas Health Science Center at Houston, Dr. Li used DaPars to identify CFIm25, a master APA regulator, as a glioblastoma tumor suppressor. In a third article, again in Nature Genetics, Dr. Li and the Goodell lab discovered extended regions of low methylation – DNA methylation canyons – that span conserved domains frequently containing transcription factors and are distinct from CpG islands and shores. Taken together, these findings have underscored the power of Dr. Li’s computational epigenetic research that can derive novel biological insights from epigenetic sequencing data.
Dr. Li's nomination was based on the following publications:
Chen K, Chen Z, Wu D, Zhang L, Lin X, Su J, Rodriguez B, Xi Y, Xia Z, Chen X, Shi X, Wang Q, Li W. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Nat Genet. 2015 Oct;47(10):1149-57. doi: 10.1038/ng.3385. Epub 2015 Aug 24.
Xia Z, Donehower LA, Cooper TA, Neilson JR, Wheeler DA, Wagner EJ, Li W. Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'-UTR landscape across seven tumour types. Nat Commun. 2014 Nov 20;5:5274. doi: 10.1038/ncomms6274.
Jeong M, Sun D, Luo M, Huang Y, Challen GA, Rodriguez B, Zhang X, Chavez L, Wang H, Hannah R, Kim SB, Yang L, Ko M, Chen R, Göttgens B, Lee JS, Gunaratne P, Godley LA, Darlington GJ, Rao A, Li W, Goodell MA. Large conserved domains of low DNA methylation maintained by Dnmt3a. Nat Genet. 2014 Jan;46(1):17-23. doi: 10.1038/ng.2836. Epub 2013 Nov 24.