Yuh-Hwa Wang


  • PhD, North Carolina State University

Primary Appointment

  • Professor, Biochemistry and Molecular Genetics


Research Interest(s)

Genome instability in human disease

Research Description

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 Publications

  • Lehman C, Dillon L, Nikiforov Y, Wang Y. DNA fragile site breakage as a measure of chemical exposure and predictor of individual susceptibility to form oncogenic rearrangements. Carcinogenesis. 2017;38(3): 293-301. PMID: 28069693
  • Chen C, Tsao N, Huang L, Yen Y, Liu X, Lehman C, Wang Y, Tseng M, Chen Y, Ho Y, Chen C, Chang Z. The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells. Cell reports. 2016;16(5): 1287-99. PMID: 27452458
  • Thys R, Lehman C, Pierce L, Wang Y. DNA secondary structure at chromosomal fragile sites in human disease. Current genomics. 2015;16(1): 60-70. PMID: 25937814 | PMCID: PMC4412965
  • Thys R, Lehman C, Pierce L, Wang Y. Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells. Mutation research. 2015;779 86-95. PMID: 26163765
  • Thys R, Wang Y. DNA Replication Dynamics of the GGGGCC Repeat of the C9orf72 Gene. The Journal of biological chemistry. 2015;290(48): 28953-62. PMID: 26463209 | PMCID: PMC4661408
  • Reddy K, Schmidt M, Geist J, Thakkar N, Panigrahi G, Wang Y, Pearson C. Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability. Nucleic acids research. 2014;42(16): 10473-87. PMID: 25147206
  • Axford M, Wang Y, Nakamori M, Zannis-Hadjopoulos M, Thornton C, Pearson C. Detection of Slipped-DNAs at the Trinucleotide Repeats of the Myotonic Dystrophy Type I Disease Locus in Patient Tissues. PLoS genetics. 2013;9(12): e1003866. PMID: 24367268 | PMCID: PMC3868534
  • Dillon L, Pierce L, Lehman C, Nikiforov Y, Wang Y. DNA topoisomerases participate in fragility of the oncogene RET. PloS one. 2013;8(9): e75741. PMID: 24040417 | PMCID: PMC3770543
  • Dillon L, Pierce L, Ng M, Wang Y. Role of DNA secondary structures in fragile site breakage along human chromosome 10. Human molecular genetics. 2013;22(7): 1443-56. PMID: 23297364 | PMCID: PMC3596854
  • Dillon L, Lehman C, Wang Y. The role of fragile sites in sporadic papillary thyroid carcinoma. Journal of thyroid research. 2012;2012 927683. PMID: 22762011 | PMCID: PMC3384961
  • Dillon L, Burrow A, Wang Y. DNA instability at chromosomal fragile sites in cancer. Current genomics. 2011;11(5): 326-37. PMID: 21286310 | PMCID: PMC2944998
  • Burrow A, Marullo A, Holder L, Wang Y. Secondary structure formation and DNA instability at fragile site FRA16B. Nucleic acids research. 2010;38(9): 2865-77. PMID: 20071743 | PMCID: PMC2875025
  • Gandhi M, Dillon L, Pramanik S, Nikiforov Y, Wang Y. DNA breaks at fragile sites generate oncogenic RET/PTC rearrangements in human thyroid cells. Oncogene. 2010;29(15): 2272-80. PMID: 20101222 | PMCID: PMC2855398
  • Wan C, Kulkarni A, Wang Y. ATR preferentially interacts with common fragile site FRA3B and the binding requires its kinase activity in response to aphidicolin treatment. Mutation research. 2010;686(1): 39-46. PMID: 20060399 | PMCID: PMC2834799
  • Burrow A, Williams L, Pierce L, Wang Y. Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites. BMC genomics. 2009;10 59. PMID: 19183484 | PMCID: PMC2642838
  • Chen C, Tsao N, Huang L, Yen Y, Liu X, Lehman C, Wang YH. The impact of dutpase on ribonucleotide reductase-induced genome instability in cancer cells Cell Reports. 16(5): 1287-1299.
  • Chen C, Tsao N, Huang L, Yen Y, Liu X, Lehman C, Wang YH. The impact of dutpase on ribonucleotide reductase-induced genome instability in cancer cells Cell Reports. 16(5): 1287-1299.