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Molecular and Cellular Biology

Houston, Texas

Image 1: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.; Image 2: By Yi LI, Ph.D.; Image 3: Mouse oocyte at meiosis I immunostained for tubulin (red) phosphop38MAPK (green) and DNA (blue). By JoAnne Richards, Ph.D.; Image 4: Expanded cumulus cell ooctye ocmplex immunostained for hyaluronan (red), TSG6 (green) and DAN (blue). By JoAnne Richards, Ph.D.; Image 5: Epithelial cells taken from a mouse mammary gland were cultured in a dish and transduced with a retrovirus expressing two genes. The green staining shows green fluorescent protein and the red staining shows progesterone receptor expression. The nucleus of each cell is stained blue. Photomicrograph taken at 200X magnification. By Sandra L. Grimm, Ph.D.; Image 6: Ovarian vasculature (red) is excluded from the granulosa cells (blue) within growing follicles (round structures); Image 7: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.
Department of Molecular and Cellular Biology
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Wei Li, Ph.D.

Wei Li, Ph.D. photoAssistant Professor
Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology

Education

Ph.D.: Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
Postdoctoral training: Dana Farber Cancer Institute/Harvard School of Public Health, Boston

Research Interest

A Genomic View of Epigenetic and Transcriptional Regulation
Our lab is focused on the design and application of statistical and computational algorithms to elucidate global epigenetic and transcriptional regulatory mechanism, by interpreting and integrating data from ChIP-chip/seq, DNA methylation, Nucleosome positioning, Alternative splicing and Motif finding.

An elaborate system of epigenetic and transcription regulation is responsible for the morphological and behavioral complexity in higher eukaryotes. This regulatory system consists of diverse trans-acting protein factors, cis-acting regulatory DNA sequences and the underlying epigenomic background, such as histone modifications, DNA methylation and Nucleosome localizations. Recently, Chromatin ImmunoPrecipitation coupled with whole genome tiled microarray (ChIP-chip) and/or next-generation sequencing (Solexa, SOLiD and 454) has evolved as a powerful and unbiased technique to study this genome-wide regulatory system. The application of this technology to multiple factors and/or in multiple conditions allows biologists to study how transcription is differentially regulated in a combinatorial manner. However, it also poses great challenges for the development of effective algorithms, the key link between massive raw data and biological hypotheses.

We developed a series of algorithms to reliably detect and annotate ChIP-enriched regions using Next-generation sequencing (MACS; Genome Biology 2008) and Affymetrix whole-genome tiling arrays, including 1) Model-based Analysis of Tiling-arrays (MAT; PNAS 2006) and a hidden Markov model (Bioinformatics 2005) for ChIP-region detection, 2) extreme MApping of OligoNucleotide (xMAN; BMC Genomics 2008) for microarray probe mapping, 3) Cis-regulatory Element Annotation System (CEAS; NAR 2006) for ChIP-region annotation. Since the inception in early 2006, they have been adopted by hundreds of academic users and are now considered as the ChIP-chip data analysis standard in many labs. We worked with ENCODE consortium to systematically analyze the performance variability introduced in ChIP-chip protocols, array platforms, and analysis methods (Genome Res. 2008). Furthermore, we are also in close collaboration with several labs on identifying global regulation targets of several key transcription factors, including Estrogen Receptor (Cell 2005; Nature Genetics 2006); Androgen Receptor (Molecular Cell 2007; Cell 2009) and FoxA1 (Cell 2008).

We are currently collaborating with many BCM laboratories to use the Next generation sequencing to study 1) Transcription factor binding (ChIP-seq); 2) DNA methylation at single nucleotide resolution (BS-seq); 3) Nucleosome positioning (Nu-seq); 4) Cancer specific alternative splicing junctions (RNA-seq). My laboratory also plays an important role in the BCM Epigenomics Data Analysis and Coordination Center for a five-year $190 million NIH Roadmap Epigenomics Program.

Contact Information

Baylor College of Medicine
One Baylor Plaza
Cullen Building, Suite 450A9
Mail Stop BCM305
Houston, TX 77030

Phone: 713-798-7854
E-mail: WL1@bcm.tmc.edu
Lab Web Site: http://lilab.openwetware.org/

Selected Publications

  1. Xi Y, Li W. (2009). BSMAP: whole genome Bisulfite Sequence MAPping program. BMC Bioinformatics. Accepted.
  2. Wang Q*, Li W*, Zhang Y, Yuan X, ..., Kantoff PW, Liu XS, Brown M. (2009). Reprogrammed Androgen Receptor Function in Androgen-Independent Prostate Cancer. Cell (* joint first authors) accepted.
  3. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nussbaum C, Myers RM, Brown M, Li W#, Liu XS# (2008). Model-based Analysis of ChIP-Seq (MACS).Genome Biol. 9 R137 (# joint corresponding authors).
  4. Johnson D*, Li W*, Gordon DB, Bhattacharjee A, Curry B, Ghosh J, Brizuela L, Carroll JS, Brown M, Flicek P et al. (2008). Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets. Genome Res.18 393-403. (* joint first authors).
  5. Li W, Carroll JS, Brown M and Liu XS. (2008).xMAN: extreme MApping of OligoNucleotides. BMC Genomics.
  6. Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS and Brown M. (2008). FoxA1 translates epigenetic signatures into lineage-specific transcription. Cell 132 958-970.
  7. Johnson WE*, Li W*, Meyer CA*, Gottardo R, Carroll JS, Brown M and Liu XS. (2006). Model-based analysis of tiling-arrays for ChIP-chip. Proc. Natl. Acad. Sci. U S A 103 12457-12462. (* joint first authors)
  8. Carroll JS, Meyer CA, Song J, Li W, Geistlinger TR, Eeckhoute J, Brodsky AS, Keeton EK, Fertuck KC, Hall GF, Wang Q, Bekiranov S, Sementchenko V, Fox EA, Silver PA, Gingeras TR, Liu XS and Brown M. (2006). Genome-wide analysis of estrogen receptor binding sites. Nat. Genet. 38 1289-1297.
  9. Ji X*, Li W*, Song J, Wei L and Liu XS. (2006). CEAS: cis-regulatory element annotation system. Nucleic Acids Res. 34 W551-554. (* joint first authors).
  10. Li W, Meyer CA and Liu XS: A hidden Markov model for analyzing ChIP-chip experiments on genome tiling arrays and its application to p53 binding sequences. Bioinformatics 21 Suppl 1 (ISMB2005) i274-i282.

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