RESEARCH

The disease myotonic dystrophy (dystrophia myotonica, DM) is one of the most common form of muscular dystrophies, and is a paradigm for a class of diseases caused by toxic RNA. We are using deep sequencing technologies, such as RNA-Seq and CLIP-Seq, in combination with molecular & cell biological techniques, to better understand how the expanded microsatellite repeat in this disease leads to a myriad of symptoms in virtually all tissues of the body, including skeletal, cardiac, and smooth muscle, and also tissues of the central nervous system.

Recently, we found that the Muscleblind-like proteins (MBNLs), which are inactivated by the toxic RNA found in DM cells, also regulate the subcellular localization of many RNA species. We study how MBNL proteins can achieve these functions, and also how RNA localization is regulated at a basic level by RNA cis-elements and protein/RNA trans-factors. We aim to use both high-throughput, global approaches and high-resolution, single molecule approaches to define a "parts list" for RNA localization.

Finally, our studies of DM pathogenesis and RNA regulation are in part driven by a desire to find treatments for DM and other related diseases. We work with diverse partners in both the academic and industrial space to make progress in this area, and are taking a number of approaches to develop therapeutics that may one day enter the clinic.

Publications

2015

  1. Eric T Wang, Amanda J Ward, Jennifer Cherone, Thomas T Wang, Jimena Giudice, Daniel Treacy, Peter Freese, Nicole J Lambert, Tanvi Saxena, Thomas A Cooper and Christopher B Burge. Antagonistic Regulation of mRNA Expression and Splicing by CELF and MBNL Proteins. Genome Res, 2015.
  2. Yarden Katz, Eric T Wang, Jacob Silterra, Schraga Schwartz, Bang Wong, Helga Thorvaldsd'ottir, James T Robinson, Jill P Mesirov, Edoardo M Airoldi and Christopher B Burge. Quantitative visualization of alternative exon expression from RNA-seq data. Bioinformatics, 2015.

2014

  1. Jimena Giudice, Zheng Xia, Eric T Wang, Marissa A Scavuzzo, Amanda J Ward, Auinash Kalsotra, Wei Wang, Xander H T Wehrens, Christopher B Burge, Wei Li and Thomas A Cooper. Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development. Nat Commun, 5: 3603, 2014.
  2. Albert W Cheng, Jiahai Shi, Piu Wong, Katherine L Luo, Paula Trepman, Eric T Wang, Heejo Choi, Christopher B Burge and Harvey F Lodish. Muscleblind-like 1 (Mbnl1) regulates pre-mRNA alternative splicing during terminal erythropoiesis. Blood, 124 (4): 598-610, 2014.
  3. J Matthew Taliaferro, Eric T Wang and Christopher B Burge. Genomic analysis of RNA localization. RNA Biol, 11 (8): 1040-50, 2014.

2013

  1. Hong Han, Manuel Irimia, P Joel Ross, Hoon-Ki Sung, Babak Alipanahi, Laurent David, Azadeh Golipour, Mathieu Gabut, Iacovos P Michael, Emil N Nachman, Eric Wang, Dan Trcka, Tadeo Thompson, Dave O'Hanlon, Valentina Slobodeniuc, Nuno L Barbosa-Morais, Christopher B Burge, Jason Moffat, Brendan J Frey, Andras Nagy, James Ellis, Jeffrey L Wrana and Benjamin J Blencowe. MBNL proteins repress ES-cell-specific alternative splicing and reprogramming. Nature, 498 (7453): 241-5, 2013.
  2. Marka van Blitterswijk, Eric T Wang, Brad A Friedman, Pamela J Keagle, Patrick Lowe, Ashley Lyn Leclerc, Leonard H van den Berg, David E Housman, Jan H Veldink and John E Landers. Characterization of FUS mutations in amyotrophic lateral sclerosis using RNA-Seq. PLoS One, 8 (4): e60788, 2013.
  3. Mohammadsharif Tabebordbar, Eric T Wang and Amy J Wagers. Skeletal muscle degenerative diseases and strategies for therapeutic muscle repair. Annu Rev Pathol, 8: 441-75, 2013.

2012

  1. Raman Parkesh, Jessica L Childs-Disney, Masayuki Nakamori, Amit Kumar, Eric Wang, Thomas Wang, Jason Hoskins, Tuan Tran, David Housman, Charles A Thornton and Matthew D Disney. Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching. J Am Chem Soc, 134 (10): 4731-42, 2012.
  2. Jamie Purcell, Julia C Oddo, Eric T Wang and J Andrew Berglund. Combinatorial Mutagenesis of MBNL1 Zinc Fingers Elucidates Distinct Classes of Regulatory Events. Mol Cell Biol, 32 (20): 4155-67, 2012.
  3. Maja M Janas, Eric Wang, Tara Love, Abigail S Harris, Kristen Stevenson, Karlheinz Semmelmann, Jonathan M Shaffer, Po-Hao Chen, John G Doench, Subrahmanyam V B K Yerramilli, Donna S Neuberg, Dimitrios Iliopoulos, David E Housman, Christopher B Burge and Carl D Novina. Reduced expression of ribosomal proteins relieves microRNA-mediated repression. Mol Cell, 46 (2): 171-86, 2012.
  4. Eric T Wang, Neal A L Cody, Sonali Jog, Michela Biancolella, Thomas T Wang, Daniel J Treacy, Shujun Luo, Gary P Schroth, David E Housman, Sita Reddy, Eric L'ecuyer and Christopher B Burge. Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins. Cell, 150 (4): 710-24, 2012.

2010

  1. Christopher S Bland, Eric T Wang, Anthony Vu, Marjorie P David, John C Castle, Jason M Johnson, Christopher B Burge and Thomas A Cooper. Global regulation of alternative splicing during myogenic differentiation. Nucleic Acids Res, 38 (21): 7651-64, 2010.
  2. Yarden Katz, Eric T Wang, Edoardo M Airoldi and Christopher B Burge. Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nat Methods, 7 (12): 1009-15, 2010.

2009

  1. Xinshu Xiao, Zefeng Wang, Minyoung Jang, Razvan Nutiu, Eric T Wang and Christopher B Burge. Splice site strength-dependent activity and genetic buffering by poly-G runs. Nat Struct Mol Biol, 16 (10): 1094-100, 2009.
  2. Daniel Ramsk"old, Eric T Wang, Christopher B Burge and Rickard Sandberg. An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data. PLoS Comput Biol, 5 (12): e1000598, 2009.

2008

  1. Eric T Wang, Rickard Sandberg, Shujun Luo, Irina Khrebtukova, Lu Zhang, Christine Mayr, Stephen F Kingsmore, Gary P Schroth and Christopher B Burge. Alternative isoform regulation in human tissue transcriptomes. Nature, 456 (7221): 470-6, 2008.

2007

  1. Guohao Dai, Saran Vaughn, Yuzhi Zhang, Eric T Wang, Guillermo Garcia-Cardena and Jr, Michael A Gimbrone. Biomechanical forces in atherosclerosis-resistant vascular regions regulate endothelial redox balance via phosphoinositol 3-kinase/Akt-dependent activation of Nrf2. Circ Res, 101 (7): 723-33, 2007.

2006

  1. Kush M Parmar, H Benjamin Larman, Guohao Dai, Yuzhi Zhang, Eric T Wang, Sripriya N Moorthy, Johannes R Kratz, Zhiyong Lin, Mukesh K Jain, Jr, Michael A Gimbrone and Guillermo Garcia-Cardena. Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J Clin Invest, 116 (1): 49-58, 2006.
  2. Deborah Abeles, Stephanie Kwei, George Stavrakis, Yuzhi Zhang, Eric T Wang and Guillermo Garcia-Cardena. Gene expression changes evoked in a venous segment exposed to arterial flow. J Vasc Surg, 44 (4): 863-70, 2006.