Li Lab

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Recent News

. 09/2017: Feng Xin and Lei Li's paper on TC3A: The Cancer 3’ UTR Atlas was accepted to Nucleic Acids Research.

. 09/2017: Hyun Jung Park has been offered a tenure-track Assistant Professor position at University of Pittsburgh Medical Center. Congratulations.

. 08/2017: Xueqiu's scUMC DNA methylation paper was accepted to Genome Biology.

. 07/2017: Jianzhong's DNA methylation editing paper was published in Nature Communications.

. 05/2017: Our TCGA Liver Cancer paper was accepted to Cell.

. 02/2017: Our Research Center for Cancer Systems Biology (CCSB U54) grant was funded by NCI, in collaboration with Qianben Wang, Victor Jin and Tim Huang.

. 02/2017: Collaborative work with Xiaobing Shi and David Allis was accepted to Nature.

. 12/2016: Graduate student Xueqiu Lin will start his postdoc position at Stanford.

. 11/2016: Jianfeng Xu has passed his qualify exam. Congratulations!

. 08/2016: Welcome our new Postdoc Associates Drs. Xiaodong Cui, Jiejun Shi and Lei Li.

. 08/16: Zheng Xia will start his tenure-track faculty position at Oregon Health & Science University (OHSU) with a million-dollar package. Congratulations!

. 07/16: Wei has been promoted to Professor of Bioinformatics at Baylor College of Medicine.

. 06/16: Xueqiu successfully defended her PhD thesis. Congratulations Dr. Lin.

. 06/16: A new paper w/ MG Lee @ MD Anderson was accepted to Molecular Cell.

. 04/16: Jianzhong's DNMT3A/TET2 paper (w/ Goodell lab) was accepted to Nature Genetics.

. 04/16: Wei has been selected as a recipient of the 2016 Michael E. DeBakey, M.D., Excellence in Research Award

. 04/16: Yuanxin has been offered a tenure-track faculty position at The University of Texas Health Science Center at Houston (UTHealth). Congratulations!

. 03/2016: Ben's enhancer hypomethylation paper (w/ Goodell lab) was accepted to Cancer Cell.

. 02/2016: Yuanxin's SIRT6 paper (w/ Chua lab at Stanford) was accepted to Nature Structural & Molecular Biology

. 01/2016: Welcome our new Postdoc Associate Dr. Jie Lyu.

. 12/2015: Yuanxin's G9a paper (w/ Shi lab at MD Anderson) was accepted to Nature Communications.

. 12/2015: Kaifu's UTX paper (w/ Lee lab at MD Anderson) was accepted to Nucleic Acids Research .

. 11/2015: We received a new NIH/NCI R01 grant (scored at 5%ile) to study 3`UTR alternations in human cancers.

. 09/2015: Welcome our new Research Associate (and potential Graduate Student) YanBing Cheng.

. 08/2015: Kaifu's Cancer Big-data analysis paper is published in Nature Genetics. This work links broad H3K4me3 to pan-cancer tumor suppressors. See reports in Nature Editor’s Blog, Cancer Discovery, (in Chinese), BCM news and OSU news; and an error we found in a Cell paper.

. 07/2015: Wei will become a regular member of the NIH GCAT (Genomics, Computational Biology and Technology) study section.

. 06/2015: Kaifu will start his tenure-track faculty position at Cornell University & Methodist Hospital. Congratulations!

. 03/2015: Kaifu's MeCP2 mCH binding paper (w/ Zoghbi lab) is accepted to PNAS.

. 3/2015: We received a NEW CPRIT grant.

. 01/2015: Deqiang, HJ and Ben's HSC novel noncoding RNA paper is accepted to Cell Stem Cell -- the 100th paper we published.


News Archive

Our lab is focused on the design and application of bioinformatics algorithms to elucidate global epigenetic mechanisms in normal development and diseases such as cancer. Our areas of expertise include 1) DNA methylation using Bisulfite-seq; 2) Epigenetic regulation using ChIP-seq; 3) Alternative Polyadenylation (APA); 4) Non-coding RNA; 5) Nucleosome organization using MNase-seq. Since establishing our own bioinformatics lab in early 2008, we have (as of September 2017)

  • Published 113 peer-reviewed papers through solid methodology development and extensive collaboration research, including 18 senior-author papers in Nature and Cell series.
  • Been well-funded with total external funding >$1.0 million per year, including 4 PI grants from NIH and Texas CPRIT: NIH R01HG007538 (2013-2018), R01CA193466 (2015-2020), U54CA217297 (2017-2022) and CPRIT RP150292 (2015-2018).
  • Mentored the first 6 postdoc trainees to start their tenure track faculty positions in prestigious research institutions in the US.

1) DNA methylation using Bisulfite-seq. Our lab developed some of the earliest and most widely used bioinformatics software to analyze whole genome bisulfite sequencing (WGBS) data, including the first WGBS mapping program BSMAP (>300 citations) and MOABS for model-based differential methylation analysis. Furthermore, we are among the first to report the sparse conserved single under-methylated CpG (scUMC) and DNA Methylation Canyon as two novel epigenetic features in the genome. scUMCs are associated with high-order chromatin structure, while canyons are large (3.5–26Kb) regions with very low (<10%) DNA methylation. Recently, our pan-cancer analysis of WGBS data followed by dCas9-mediated methylation editing, reveals gene-body canyon hyper-methylation as a novel epigenetic mechanism for oncogene activation. In collaboration with Goodell lab at Baylor, we are among the first to study de novo DNA methyltransferase 3A (Dnmt3a) using WGBS in normal and malignant hematopoietic stem cells (HSCs). Our collaboration reveals that Dnmt3a is essential for HSC differentiation, aging, normal function and transformation to cancers.

2) Epigenetic Regulation using ChIP-seq. Our lab developed some of the most widely cited bioinformatics methods to analyze ChIP-seq data, including MACS for Model-based Analysis of ChIP-seq (>3,800 citations) and MACE for Model based Analysis of ChIP-exo with single nucleotide resolution. Using MACS, we recently discovered Broad H3K4me3 (wider than 4 kb) as a novel epigenetic signature for tumor suppressor genes, such as TP53 and PTEN, through integrative analysis of 1,134 genome-wide epigenetic profiles from ENCODE, mutations from >8,200 tumor-normal pairs from TCGA and our own experimental data from clinical samples. In collaboration with several experimental biologists, we used ChIP-seq to gain novel biological insights into the genome-wide functions of several important epigenetic enzymes, including AR, Atoh1, FoxA1, NSD2, SIRT7, ZMYND11, YEATS, MeCP2, ZMYND8, SIRT6 and ENL.

3) Alternative Polyadenylation (APA). By changing the position of polyadenylation, APA can generate transcripts with diverse 3’ UTRs that contain different cis-regulatory elements, such as miRNA binding sites, leading to altered function, stability and translation efficiency of target RNAs. The role of APA in human diseases such as cancer is only beginning to be appreciated. This is mainly because polyA profiling methods (PolyA-seq) have not been widely adopted. To overcome these limitations, we developed the first bioinformatics algorithm DaPars for Dynamic Analyses of Alternative Polyadenylation directly from the widely-used RNA-Seq. In collaboration with Wagner lab at UTMB, we used DaPars to identify CFIm25, a master APA regulator, as a glioblastoma (GBM) tumor suppressor, underscoring the importance of APA in cancer development. Furthermore, our recent re-analysis of TCGA breast cancer data suggests that the major role of 3ʹ-UTR shortening in tumorigenesis is to repress tumor suppressor genes in trans by disrupting competing-endogenous RNA (ceRNA) crosstalk.

4) Non-coding RNAs using RNA-seq. Deep RNA-seq has been widely used to detect tens of thousands of novel RNAs beyond traditional protein coding genes. Our lab developed some of the most widely used bioinformatics methods to analyze such RNA-seq data, including RNA-seq quality control program RseQC (>300 citations) and the first alignment-free coding-potential assessment tool CPAT (>240 citations). In collaboration with several experimental biologists, we reported hundreds of non-coding RNAs that are important for hematopoietic stem cells (HSCs) self-renewal and lineage commitment, and found a high percentage of sequence reads in introns, leading to loss of function through nonsense-mediated decay in castration-resistant prostate cancer (CRPC) bone marrow biopsy specimens.

5) Nucleosome Organization using MNase-seq. The physical organization of nucleosomes can “reprogram” the underlying DNA to promote or block multiple chromatin-associated cellular functions, such as transcription. MNase digestion of chromatin followed by high throughput sequencing (MNase-seq) is a popular method to understand such nucleosome organization in the genome. Our lab developed a novel bioinformatics pipeline, DANPOS, to aid in better understanding how the nucleosome is removed to allow transcription in different environmental conditions. We used DANPOS to study nucleosome dynamics in various cellular functions and disease processes, such as nucleosome fragility, embryonic stem cell (ESC) differentiation, aging, and promoter nucleosomes in previous reported nucleosome-free regions.

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