Janet E. Mertz, Ph.D. Professor Department of Oncology mertz@oncology.wisc.edu

Research Interests:

One of our group’s long-term interests involves transcriptional regulation of the genes of the primate DNA tumor viruses simian virus 40 (SV40), hepatitis B virus (HBV) and Epstein-Barr virus (EBV) that have been implicated in a variety of human cancers. We have found that members of the steroid/thyroid/retinoid hormone receptor superfamily play direct roles in regulating transcription and replication of SV40 and HBV, indicating that appropriate analogues of ligands to these receptors may prove useful as anti-viral drugs for the treatment of acute and chronic infections by some viruses. Recently, we have identified new factors including ZEB1 (deltaEF1) and ZEB2 (SIP1), that play crucial roles in the establishment and maintenance of EBV latency and reactivation of EBV into replication. Understanding the activities of these factors and how they are altered via cell signaling pathways may lead to new therapies for treating some EBV-associated diseases including lymphomas and carcinomas.

Our group’s second area of research concerns the roles of the human estrogen-related receptor a(ERRa) in regulation of estrogen responsiveness and breast carcinogenesis. We have found that ERRa can function either as a down-modulator or a constitutive activator of estrogen response element-directed transcription, with its activity likely regulated in part by post-translational modifications occurring via ErbB2 signaling pathways. We have also determined that ERR_ is likely a major player in the subset of breast cancers lacking estrogen receptor activity or resistant to tamoxifen. Thus, understanding how ERR_’s activities are affected by signaling pathways may lead to the development of additional tools for prognosis and therapeutic treatments, especially for ER-negative and tamoxifen-resistant breast cancers.

Selected Recent Publications: Articles on PubMed

• Vu EH, Kraus RJ, and Mertz JE. (2007). Phosphorylation-Dependent Sumoylation of Estrogen-Related Receptor alpha1. Biochem. 46:9795-9804. PMID 17676930
  
  
• Feng WH, Kraus RJ, Dickerson SJ, Lim HJ, Jones RJ, Yu X, Mertz JE, and Kenney SC. (2007). ZEB1 and c-Jun Levels Contribute to the Establishment of Highly Lytic Epstein-Barr Virus Infection in Gastric AGS Cells. J Virol. 81:10113-10122. PDF PMID 17626078
  
  
• Ariazi EA, Kraus RJ, Farrell ML, Jordan VC, and Mertz JE. (2007). Estrogen-related receptor alpha1 transcriptional activities are regulated in part via the ErbB2/HER2 signaling pathway. Mol Cancer Res. 5:71-85. PDF PMID 17259347
  
  
• Yu XM, Wang Z, and Mertz JE. (2007). ZEB1 regulates the latent-lytic switch in infection by Epstein-Barr virus. PLoS Pathog. 3:194. PMID 18085824

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