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Research Interests: Transcriptional regulation in DNA tumor viruses and breast cancer

Research Description: One of our group's long-term interests involves regulation of gene expression and mechanisms of oncogenesis by DNA tumor viruses implicated in a variety of human cancers. Recently, we have identified the cellular transcription factor ZEB-1 as a key player in establishment and maintenance of latency following primary infection, reactivation out of latency and, possibly, malignant transformation of cells by the human herpesvirus Epstein-Barr virus. These studies could lead to the development of new ZEB-based therapies for the treatment of EBV-associated diseases such as infectious mononucleosis, nasopharyngeal carcinoma, and some lymphomas.

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 as either a down-modulator or a constitutive activator of estrogen response element-directed transcription, with its activity regulated in part by post-translational phosphorylations occurring via EGFR/ErbB2 (HER2) signaling pathways. ERRa-positivity has been shown to be associated with poor prognosis and tamoxifen resistance in breast cancer. This finding is likely due to the active form of ERRa substituting for estrogen receptor to activate genes regardless of the presence of ligands. We are currently working to develop reagents that specifically detect the activator form of ERRa in primary breast tumors for use in prognosis and determination of best currently available therapeutic options for treatment of individual breast cancers. We also hope to identify drugs that can interfere with ERRa's functional activities for use as a novel therapy, especially for the treatment of ER-negative and tamoxifen-resistant breast cancers for which there are currently a paucity of good therapeutic options.

Selected recent publications

Hyde, J. S., and Mertz, J. E.  Gender, Culture, and Mathematics Performance.  Proc. Natl. Acad. Sci. USA, 106: 8801-8807, 2009.

Andreescu, T., Gallian, J. A., and Mertz, J. E.  Identifying and Cultivating Extraordinary Mathematical Talent.  Teachers College Record, November 26, 2008.  http://www.tcrecord.org  ID Number: 15454

Andreescu, T., Gallian, J. A., Kane, J. M., and Mertz, J. E.  Cross-Cultural Analysis of Students with Exceptional Talent in Mathematical Problem Solving.  Notices of the AMS, 55: 1248-1260, 2008.

Ariazi, E. A., Kraus, R. J., Farrell, M. L., Jordan, V. C., and Mertz, J. E.  Estrogen-Related Receptor a1 Transcriptional Activities Are Regulated in Part via the ErbB2/HER2 Signaling Pathway.  Mol. Cancer Res., 5:  71-85, 2007.

Feng, W.-h., Kraus, R. J., Dickerson, S. J., Lim, H. J., Jones, R. J., Yu, X., Mertz, J. E., and Kenney, S. C.  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, 2007.

Vu, E. H., Kraus, R. J., and Mertz, J. E.  Phosphorylation-Dependent Sumoylation of Estrogen-Related Receptor a1.  Biochemistry, 46:  9795-9804, 2007.

Yu, X., Wang, Z., and Mertz, J. E.  ZEB1 Regulates the Latent-Lytic Switch in Infection by Epstein-Barr Virus.  PLoS Pathog., 3:e194, 2007.

Guang, S., and Mertz, J. E. Pre-mRNA Processing Enhancer (PPE) Elements from Intronless Genes Play Additional Roles in mRNA Biogenesis Than Do Ones from Intron-containing Genes. Nucleic Acids Res., 33: 2215-2226, 2005.

Guang, S., Felthauser, A. M., and Mertz, J. E. Binding of hnRNP L to the Pre-mRNA Processing Enhancer of the Herpes Simplex Virus Thymidine Kinase Gene Enhances Both Polyadenylation and Nucleocytoplasmic Export of Intronless mRNAs. Mol. Cell. Biol., 25: 6303-6313, 2005.

Kraus, R. J., Perrigoue, J. G., and Mertz, J. E. ZEB Negatively Regulates the Lytic-Switch BZLF1 Gene Promoter of Epstein-Barr Virus. J. Virol., 77: 199-207, 2003.

Yu, X., and Mertz, J. E. Distinct Modes of Regulation of Transcription of Hepatitis B Virus by the Nuclear Receptors HNFa and COUP-TF1. J. Virol., 77: 2489-2499, 2003.

Ariazi, E. A., Clark, G. M., and Mertz, J. E. Estrogen-related Receptor a and Estrogen-related Receptor g Associate with Unfavorable and Favorable Biomarkers, Respectively, in Human Breast Cancer. Cancer Res., 62: 6510-6518, 2002.

Farrell, M. L., and Mertz, J. E. Cell Type-Specific Replication of Simian Virus 40 Conferred by Hormone Response Elements in the Late Promoter. J. Virol., 76: 6762-6770, 2002.

Farrell, M. L., and Mertz, J. E. Hormone Response Element in SV40 Late Promoter Directly Affects Synthesis of Early as Well as Late Viral RNAs. Virology, 297: 307-318, 2002.

Kraus, R. J., Ariazi, E. A., Farrell, M. L., and Mertz, J. E. Estrogen-related Receptor a1 Actively Antagonizes Estrogen Receptor-regulated Transcription in MCF-7 Mammary Cells. J. Biol. Chem., 277: 24826-24834, 2002.

Kraus, R. J., Mirocha, S. J., Stephany, H. M., Puchalski, J. R., and Mertz, J. E. Identification of a Novel Element Involved in Regulation of the Lytic Switch BZLF1 Gene Promoter of Epstein-Barr Virus.  J. Virol., 75:  867-877, 2001.

Kraus, R. J., Shadley, L., and Mertz, J. E. Nuclear Factor 1 Family Members Mediate Repression of the BK Virus Late Promoter. Virology, 287: 89-104, 2001.

Yu, X., and Mertz, J. E. Critical Roles of Nuclear Receptor Response Elements in Replication of Hepatitis B Virus. J. Virol., 75: 11354-11364, 2001.