Yuh-Hwa Wang
Associate Professor of Biochemistry
Ph.D. North Carolina State
Human fragile sites in cancer; Trinucleotide repeat expansion diseases


Our research focus is to understand the structure and function of unusual DNA sequences in living cells, and how these sequences cause genome instability and 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 the 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 for which 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, and electron Microscopy.

Selected References

Dillon LW, Pierce LC, Lehman CE, Nikiforov YE, Wang YH. (2013) "DNA Topoisomerases Participate in Fragility of the Oncogene RET." PLoS One. Sep 8:e75741. doi: 10.1371/journal.pone.0075741. [PubMed]

Dillon LW, Pierce LC, Ng MC, Wang YH. (2013) "Role of DNA secondary structures in fragile site breakage along human chromosome 10." Hum Mol Genet. Apr 22:1443-56. doi: 10.1093/hmg/dds561. Epub 2013 Jan7. [PubMed]

Dillon LW, Lehman CE, Wang YH. (2012) "The role of fragile sites in sporadic papillary thyroid carcinoma." J Thyroid Res. 2012:927683. doi: 10.1155/2012/927683. Epub 2012 Jun 11. [PubMed]

Weckerle AB, Santra M, Ng MC, Koty PP, Wang YH. (2011) "CBFB and MYH11 in inv(16)(p13q22) of acute myeloid leukemia displaying close spatial proximity in interphase nuclei of human hematopoietic stem cells." Genes Chromosomes Cancer. 50:746-55. doi: 10.1002/gcc.20896. Epub2011 Jun 2. [PubMed]

Dillon LW, Burrow AA, Wang YH. (2010) "DNA instability at chromosomal fragile sites in cancer." Curr Genomics. 11:326-37. doi: 10.2174/138920210791616699. [PubMed]

Gandhi M, Dillon LW, Pramanik S, Nikiforov YE, Wang YH. (2010) "DNA breaks at fragile sites generate oncogenic RET/PTC rearrangements in human thyroid cells." Oncogene. Apr 29(15):2272-80. doi: 10.1038/onc.2009.502. Epub 2010 Jan25. [PubMed]

Li G, Margueron R, Hu G, Stokes D, Wang YH, Reinberg D. (2010) "Highly compacted chromatin formed in vitro reflects the dynamics of transcription activation in vivo." Mol Cell. Apr 38:41-53. doi: 10.1016/j.molcel.2010.01.042. [PubMed]

Burrow AA, Marullo A, Holder LR, Wang YH. (2010) "Secondary structure formation and DNA instability at fragile site FRA16B." Nucleic Acids Res. 38:2865-77. doi: 10.1093/nar/gkp1245. Epub 2010Jan 13. [PubMed]

Wan C, Kulkarni A, Wang YH. (2010) "ATR preferentially interacts with common fragile site FRA3B and the binding requires its kinase activity in response to aphidicolin treatment." Mutat Res. Apr 686(1-2):39-46. doi: 10.1016/j.mrfmmm.2009.12.012. Epub2010 Jan 7. [PubMed]

Burrow AA, Williams LE, Pierce LC, Wang YH. (2009) "Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites." BMC Genomics. Jan 10:59. doi: 10.1186/1471-2164-10-59. [PubMed]

Hagerman KA, Ruan H, Edamura KN, Matsuura T, Pearson CE, Wang YH. (2009) "The ATTCT repeats of spinocerebellar ataxia type 10 display strong nucleosome assembly which is enhanced by repeat interruptions." Gene. Apr 434(1-2):29-34. doi: 10.1016/j.gene.2008.12.011. Epub 2008 Dec25. [PubMed]

Ruan H, Wang YH. (2008) "Friedreich's ataxia GAA.TTC duplex and GAA.GAA.TTC triplex structures exclude nucleosome assembly." J Mol Biol. Nov 383:292-300. doi: 10.1016/j.jmb.2008.08.053. Epub 2008 Aug 27. [PubMed]

Trojer P, Li G, Sims RJ 3rd, Vaquero A, Kalakonda N, Boccuni P, Lee D,Erdjument-Bromage H, Tempst P, Nimer SD, Wang YH, Reinberg D. (2007) "L3MBTL1, a histone-methylation-dependent chromatin lock." Cell. Jun 129:915-28. [PubMed]