B.S., B.S., 1970, Life Sciences/Electrical Engineering, Massachusetts Institute of Technology
Ph.D., 1975, Biochemistry, Stanford University
Postdoctoral research: Medical Research Council Laboratory of Molecular Biology, Cambridge, England
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 factors ZEB-1 and Ikaros as key players in maintaining the human herpesvirus Epstein-Barr virus (EBV) in a latent state while BLIMP1 and HIF-1α are major physiological players in reactivating this virus into lytic replication during epithelial and B-cell differentiation and hypoxic conditions, respectively. In collaboration with the Kenney laboratory, we are identifying and testing some drugs and drug combinations that might prove useful as new therapeutic agents for treating patients with a variety of EBV-associated cancers. Our group's second area of research concerns the roles of estrogen-related receptor α (ERRα) in regulation of estrogen responsiveness and breast carcinogenesis. We have found that ERRα can function as either a down-modulator or constitutive activator of estrogen response element-directed transcription, with its activity regulated by post-translational modifications controlled by cellular signaling pathways, not ligands; it can also form heterodimers with estrogen receptor α (ERα). ERRα-positivity is associated with poor prognosis and tamoxifen resistance in breast cancer. This finding is likely due to ERRα substituting for ERα to activate ERα–responsive genes even when tamoxifen is presence. We are working to develop reagents that specifically detect ERRα in primary breast tumors for use in prognosis and determination of best therapeutic options for individualized treatment of breast cancer patients.
Jones RJ, Iempridee T, Wang X, Lee HC, Mertz JE, Kenney SC, Lin HC, Baladandayuthapani V, Dawson CW, Shah JJ, Weber DM, Orlowski RZ. Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression. Clin Cancer Res. 2016 Oct 1;22(19):4901-4912. PubMed PMID: 27297582; PubMed Central PMCID: PMC5050094.
Nawandar DM, Wang A, Makielski K, Lee D, Ma S, Barlow E, Reusch J, Jiang R, Wille CK, Greenspan D, Greenspan JS, Mertz JE, Hutt-Fletcher L, Johannsen EC, Lambert PF, Kenney SC. Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells. PLoS Pathog. 2015 Oct 2;11(10):e1005195. doi: 10.1371/journal.ppat.1005195. eCollection 2015 Oct. PubMed PMID: 26431332; PubMed Central PMCID: PMC4592227.
Reusch JA, Nawandar DM, Wright KL, Kenney SC, Mertz JE. Cellular differentiation regulator BLIMP1 induces Epstein-Barr virus lytic reactivation in epithelial and B cells by activating transcription from both the R and Z promoters. J Virol. 2015 Feb;89(3):1731-43. doi: 10.1128/JVI.02781-14. Epub 2014 Nov 19. PubMed PMID: 25410866; PubMed Central PMCID: PMC4300755.
Iempridee, T., Reusch, J. A., Riching, A., Johannsen, E. C., Dovat, S., Kenney, S. C., and Mertz, J. E. Epstein-Barr Virus Utilizes Ikaros in Regulating Its Latent-Lytic Switch in B Cells. J. Virol., 88(9): 4811-4827, 2014.
Kenney, S. C., and Mertz, J. E. Regulation of the Latent-Lytic Switch in Epstein-Barr Virus. Semin. Cancer Biol., 26(C): 60-68, 2014.
Pahlke, E., Shibley Hyde, J., and Mertz, J. E. The Effects of Single-Sex Compared with Coeducational Schooling on Mathematics and Science Achievement: Data from Korea. J. Educ. Psychol., 105(2): 444-452, 2013.
Das, S., Becker, B. N., Hoffmann, F. M., and Mertz, J. E. Reversal of Transforming Growth Factor-β Induced Epithelial-to-Mesenchymal Transition and the ZEB Proteins. Fibrogenesis Tissue Repair, 5(Suppl 1): S28, 2012.
Esch, A. M., Thompson, N. E., Lamberski, J. A., Mertz, J. E., and Burgess, R. R. Production and Characterization of Monoclonal Antibodies to Estrogen-Related Receptor Alpha (ERRα) and Use in Immunoaffinity Chromatography. Protein Expr. Purif., 84: 47-58, 2012.
Kane, J. M., and Mertz, J. E. Debunking Myths About Gender and Mathematics Performance. Notices of the Am. Math. Soc., 59: 10-21, 2012. http://www.ams.org/notices/201201/rtx120100010p.pdf
Ma, S.-D., Yu, X., Mertz, J. E., Gumperz, J. E., Reinheim, E., Zhou, Y., Tang, W., Burlingham, W. J., Gulley, M. L., and Kenney, S. C. An Epstein-Barr Virus (EBV) Mutant with Enhanced BZLF1 Expression Causes Lymphomas with Abortive Lytic EBV Infection in a Humanized Mouse Model. J. Virol., 86: 7976-7987, 2012.
Yu, X., McCarthy, P. J., Wang, Z., Gorlen, D. A., and Mertz, J. E. Shutoff of BZLF1 Gene Expression Is Necessary for Immortalization of Primary B Cells by Epstein-Barr Virus. J. Virol., 86: 8086-8096, 2012.