Weidong Wang, Ph.D.
Laboratory of Genetics
251 Bayview Boulevard
Baltimore, MD 21224
The Genome Instability and Chromatin Remodeling Section (GICRS), led by Weidong Wang, focuses on three main projects: (1) protein complexes involved in genome instability diseases and the DNA damage response, (2) an RNA topoisomerase complex that works with the Fragile X syndrome protein (FMRP) to promote neuronal development, and (3) chromatin-remodeling complexes that regulate transcription, replication and repair. The Section has a strong interest in nucleic acid remodeling complexes that play essential roles in DNA transcription, replication, and repair, as well as in mRNA translation. Because many of these processes affect life span, and their defects can cause age-related disorders, genome instability syndromes, and cancer, the Section investigates if DNA and RNA remodeling complexes play crucial roles in maintaining normal aging and preventing premature aging disorders. The team has used biochemical approaches to define targeted nucleic acid-remodeling complexes from mammalian cell extracts; using this method, they have successfully identified components of the Fanconi anemia core complex, Bloom syndrome complex, ATRX-syndrome complex, FANCM-MHF DNA remodeling complex, RNF8-FAAP20 ubiquitin cascade, several chromatin-remodeling complexes (BAF, PBAF, NURD), and Top3b-TDRD3 topoisomerase complexes. Given that Top3b is the first RNA topoisomerase identified in eukaryotes, the group is working to elucidate how it functions with its partners, TDRD3 and FMRP (Fragile X syndrome proteins), to solve topological problems in RNA metabolism.
Dr. Wang was trained as a biochemist and a molecular biologist at both UCLA, where he obtained his Ph.D., and Stanford University, where he worked as a postdoctoral fellow. His research has focused on the regulation of mammalian gene expression at the chromatin level. He has purified to homogeneity one of the first ATP-dependent chromatin-remodeling complexes in mammals, and has subsequently cloned all the subunits within one complex. His current projects include characterization of novel chromatin-remodeling complexes involved in human ATRX syndrome (X-linked mental retardation and a-thalassemia); helicase complexes involved in the Werner premature aging syndrome, Bloom syndrome, and Rothmund-Thompson syndrome; and a ubiquitin ligase complex involved in a genomic instability disease, Fanconi anemia.
Yan Z, Guo R, Paramasivam M, Shen W, Ling C, Fox D 3rd, Wang Y, Oostra AB, Kuehl J, Lee DY, Takata M, Hoatlin ME, Schindler D, Joenje H, de Winter JP, Li L, Seidman MM, Wang W. A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network. Mol Cell. 2012;47(1):61-75.
Xu D, Muniandy P, Leo E, Yin J, Thangavel S, Shen X, Ii M, Agama K, Guo R, Fox D 3rd, Meetei AR, Wilson L, Nguyen H, Weng NP, Brill SJ, Li L, Vindigni A, Pommier Y, Seidman M, Wang W. Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication. EMBO J. 2010;29(18):3140-55.
Ahmad M, Xue Y, Lee SK, Martindale JL, Shen W, Li W, Zou S, Ciaramella M, Debat H, Nadal M, Leng F, Zhang H, Wang Q, Siaw GE, Niu H, Pommier Y, Gorospe M, Hsieh TS, Tse-Dinh YC, Xu D, Wang W. RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals. Nucleic Acids Res. 2016;44(13):6335-49.
Xu D, Shen W, Guo R, Xue Y, Peng W, Sima J, Yang J, Sharov A, Srikantan S, Yang J, Fox D 3rd, Qian Y, Martindale JL, Piao Y, Machamer J, Joshi SR, Mohanty S, Shaw AC, Lloyd TE, Brown GW, Ko MS, Gorospe M, Zou S, Wang W. Top3β is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation. Nat Neurosci. 2013;16(9):1238-47.
Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005;37(9):958-63.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on October 13th, 2017