Our research focus is to understand the structure and function of unusual DNA sequences in living cells and how these sequences lead to human diseases. Human chromosomal fragile sites have been correlated with the chromosomal deletions and gene rearrangements found in many cancers. Our studies are aimed at understanding the genesis of breakpoints that occur at or near fragile sites during oncogenesis. Ongoing projects include examining chromatin structure of cancer-specific fragile sites and their involvement in DNA replication/cell cycle checkpoints, and investigating the mechanism of RET/PTC rearrangement. We are also interested in the nature of trinucleotide repeat expansion diseases, in which an expanded trinucleotide repeat block is present in a gene whose loss or alteration leads to the disease. Our effort is to examine the role of chromatin structure in the pathology of these diseases, and to investigate the role of DNA structure in the mechanism of the repeat expansion. Trainees in my laboratory will gain knowledge about chromatin biology, DNA repair, and cancer-causing gene rearrangements, and will develop expertise in cell culture, molecular biology techniques for proteins and nucleic acids, cytogenetic analysis, electron microscopy, and image analysis.
CHROMOSOMAL FRAGILE SITES AND CANCER:
Ghandi, M, Dillon, L. W., Pramanlk, S., Nikiforov, Y. E., and Wang, Y.-H. (2010) DNA Breaks at Fragile Sites Generate Oncogenic RET/PTC Rearrangements in Human Thyroid Cells. Oncogene, In press.
Burrow, A. A., Marullo, A., Holder, R. L.,and Wang, Y.-H. (2010) Secondary Structure Formation and DNA Instability at Fragile Site FRA16B, Nucl. Acids. Res., In press.
Wan, C., Kulkarni, A., and Wang. Y.-H. (2010) ATR Preferentially Interacts with Common Fragile Site FRA3B in an ATR Dosage- and Kinase Activity-Dependent Manner. Mutation Research, 686:39-46. http://dx.doi.org/10.1016/j.mrfmmm.2009.12.012
Burrow, A. A., Williams, L. E., Pierce, L. C. T., and Wang, Y.-H. (2009) Over Half of Breakpoints in Gene Pairs Involved in Cancer-Specific Recurrent Translocations are Mapped to Human Chromosomal Fragile Sites. BMC Genomics, 10:59, http://www.biomedcentral.com/1471-2164/10/59.
Wang, Y.-H. (2007) Role of DNA Packaging on Rare Fragile Site Expression. In “Common and Rare Fragile Sites”, Ed. I. Arrieta, & G. R. Sutherland, Nova Science Publishers Inc. NY.
Wang, Y.-H. (2006) Chromatin Structure of Human Chromosomal Fragile Sites. Cancer Letters 232:70-78.
Mulvihill, D. J., and Wang, Y.-H. (2004) Two Breakpoint Clusters at Fragile Site FRA3B Form Phased Nucleosomes. Genome Research. 14:1350-1357. http://genome.cshlp.org/content/14/7/1350
Hsu, Y., and Wang, Y.-H. (2002) Human Fragile Site FRA16B DNA Excludes Nucleosomes in the Presence of Distamycin. J. Biol. Chem. 277:17315-17319. http://www.jbc.org/cgi/content/full/277/19/17315
TRINUCLEOTIDE REPEAT EXPANSION DISEASES:
Hagerman, K. A., Ruan, H., Edamura, K. N., Matsuura, T., Christopher E. Pearson, C. E., and Wang, Y.-H. (2009) Interruptions in the ATTCT repeats of spinocerebellar ataxia type 10 enhance nucleosome assembly. Gene 434:29-34. http://dx.doi.org/10.1016/j.gene.2008.12.011
Ruan, H., and Wang, Y.-H. (2008) Friedreich¹s ataxia GAA•TTC duplex and GAA•GAA•TTC triplex structures exclude nucleosome assembly. J. Mol. Biol. 383: 292-300. doi:10.1016/j.jmb.2008.08.053
Wang, Y.-H. (2007) Chromatin Structure of Repeating CTG/CAG and CGG/CCG Sequences in Human Diseases. In “DNA Structures, Genome Instability and Human Disease”, Ed. S. M. Mirkin, Frontiers in Biosciences 12:4731-4741.
Mulvihill, D. J., Nichol, K., Hagerman, K. A., Pearson, C. E., and Wang, Y.-H. (2005) Effect of CAT or AGG Interruptions and CpG Methylation on Nucleosome Assembly on Triplet Repeats of SCA1 and FRAXA. J. Biol. Chem. 280:4498-4503. http://www.jbc.org/cgi/content/full/280/6/4498
Lowrimore, P., D. J. Mulvihill, Epstein, A., McCormack, M., Wang, Y.-H. (2004) CAG Nucleotide Repeat Profiles in Persons with Schizophrenia or Schizoaffective Disorders With and Without Tardive Dyskinesia: Pilot Study. Am. J. of Med. Genet. 128:15-18.
Pearson, C. E., Tam, M., Wang, Y.-H., Montgomery, S. E., Dar, A. C., Cleary, J. D., and Nichol, K. (2002) Slipped-strand DNAs Formed by Long (CAG)·(CTG) Repeats: Slipped-out Repeats and Slip-out Junctions. Nucl. Acids. Res. (cover) 30: 4534-4547. http://nar.oxfordjournals.org/cgi/content/full/30/20/4534
Cleary, J., Nichol, K., Wang, Y.-H. and Pearson, C. E. (2002) Replication Fork Dynamics and Dynamic Mutations of (CTG)•(CAG) Repeats: Evidence of Cis-Acting Factors. Nature Genetics 31:37-46. http://www.nature.com/ng/journal/v31/n1/abs/ng870.html
Wang, Y.-H. (2000) DNA structures of Biological Relevance, Studies of unusual sequences. In “Encyclopedia of Analytical Chemistry: Instrumentation and Applications”, Ed. R. A. Meyers.
CHROMATIN REMODELING AND TRANSCRIPTION:
Trojer, P., Li, G., Sims, R. J., Vaquero, A., Kalakonda, N., Boccuni, P., Lee, D., Erdjument-Bromage, H., Tempst, P., Nimer, S., Wang, Y.-H., and Reinberg, D. (2007) L3MBTL1, a histone methylation dependent chromatin lock. Cell, 129: 915-928. doi:10.1016/j.cell.2007.03.048
Rubtsov, M. A., Polikanov, Y. S., Bondarenko, V. A., Wang, Y.-H., and Studitsky, V. M. (2006) Chromatin Structure Can Strongly Facilitate Enhancer Action Over a Distance. Proc. Natl. Acad. Sci. U.S.A. 103:17690-17695. http://www.pnas.org/content/103/47/17690
Loyola, A., Huang, J.-Y., LeRoy, G., Hu, S., Wang, Y.-H., Donnelly, R. J., Lane, W., Lee, S.-C., and Reinberg, D. (2003) Functional Analysis of The Subunits of The Chromatin Assembly Factor RSF. Mol. Cell. Biol. 23:6759-6768. http://mcb.asm.org/cgi/content/full/23/19/6759?view=long&pmid=12972596
Loyola, A., LeRoy, G., Wang, Y.-H. and Reinberg, D. (2001) Reconstitution of Recombinant Chromatin Establishes a Requirement for Histone-Tail Modifications During Chromatin Assembly and Transcription. Gene & Dev. 15: 2837-2851. http://genesdev.cshlp.org/content/15/21/2837
Contact Info and Recent publications