Hans-Ulrich Bernard

picture of Hans-Ulrich  Bernard

Professor, Molecular Biology and Biochemistry
School of Biological Sciences

Ph.D., University of Goettingen, Germany

Phone: (949) 824-5162
Fax: (949) 824-8551
Email: hbernard@uci.edu

University of California, Irvine
114 Sprague Hall
Mail Code: 3905
Irvine, CA 92697
Research Interests
Papillomaviruses and cervical cancer
Research Abstract
Human papillomaviruses (HPVs) cause neoplasia of infected epithelia. Some HPV types cause only benign lesions, for example common warts. However, several “high-risk” HPV types, such as HPV-16 and HPV-18, are important public health problems, since they are the primary cause of cancer of the cervix and other anogenital and oral sites. Most men and women become infected during part of their lives by “high-risk” HPV types, but with few exceptions, the virus is carcinogenic only in women and only in a fraction of the infected individuals.

Several still poorly understood mechanisms determine whether HPV infections remain latent, benign, or progress malignantly. Some of these mechanisms are based on the regulation of the HPV oncogene transcription. The gene expression of HPVs is regulated in a very complex manner, in spite of the small size of viral DNA genomes, and involves many sequence specific transcription factors, which determine properties like epithelial specificity of HPV transcription, hormonal regulation, and negative feedback loops. Beyond regulation by these factors, there is now increasing evidence that the viral life cycle as well as HPV dependent tumor progression are governed by phenomena that are independent of sequence specific factors but rather determined by epigenetic mechanisms such as DNA methylation.

HPV DNA often becomes methylated and thereby transcriptionally repressed, and we are studying how HPV genomes are recognized by the cellular methylation machinery and how methylation and demethylation correlate with the viral life cycle and cancer progression. Specifically, we observed that the HPV L1 gene becomes hyper-methylated in cancers and high-grade precursor lesions, and we are investigating in collaborative etiological and epidemiological studies the power of this biomarker for monitoring disease progression.

Additional recent directions of the lab include research of the synergistic effects of tobacco smoking and HPVs in carcinogenesis, and collaboration with other groups at UCI to understand the humoral immune response against HPV infections.
Van Doorslaer K, Bernard HU, Chen Z, de Villiers EM, zur Hausen H, Burk RD. Papillomaviruses: evolution, Linnaean taxonomy and current nomenclature. Trends Microbiol. 2011 Feb;19(2):49-50; author reply 50-1. Epub 2010 Dec 7.
Luevano M, Bernard HU, Barrera-Saldaña HA, Trevino V, Garcia-Carranca A, Villa LL, Monk BJ, Tan X, Davies DH, Felgner PL, Kalantari M.2. High-throughput profiling of the humoral immune responses against thirteen human papillomavirus types by proteome microarrays.Virology. 2010 Sep 15;405(1):31-40. Epub 2010 Jun 15.
Bernard HU, Burk RD, Chen Z, van Doorslaer K, Hausen H, de Villiers EM.Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments.Virology. 2010 May 25;401(1):70-9. Epub 2010 Mar 5.
Kalantari M, Chase DM, Tewari KS, Bernard HU.Recombination of human papillomavirus-16 and host DNA in exfoliated cervical cells: a pilot study of L1 gene methylation and chromosomal integration as biomarkers of carcinogenic progression.
J Med Virol. 2010 Feb;82(2):311-20.
Kalantari M, Garcia-Carranca A, Morales-Vazquez CD, Zuna R, Montiel DP, Calleja-Macias IE, Johansson B, Andersson S, Bernard HU.Laser capture microdissection of cervical human papillomavirus infections: copy number of the virus in cancerous and normal tissue and heterogeneous DNA methylation.
Virology. 2009 Aug 1;390(2):261-7. Epub 2009 Jun 4.
Calleja-Macias, I.E., Kalantari, M., Bernard, H.U. Cholinergic signaling through nicotinic acetylcholine receptors stimulates the proliferation of cervical cancer cells: An explanation for the molecular role of tobacco smoking in cervical carcinogenesis? Intern. J. Cancer 124, 1090-1096 (2009).
Kalantari, M., Villa, L.L., Calleja-Macias, I.E., Bernard, H.U. Human Papillomavirus-16 and 18 in penile carcinomas: DNA methylation, chromosomal recombination, and genomic variation. Intern. J. Cancer 123, 1832-1840 (2008).
Turan, T., Kalantari, M., Cuschieri, K., Cubie, H.A., Skomedal, H., Bernard, H.U. High-throughput detection of human papillomavirus-18 L1 gene methylation, a candidate biomarker for the progression of cervical neoplasia. Virology 361, 185-193 (2007).
Bernard, H.U., Calleja-Macias, I.E., Dunn, S.T. Genome variation of human papillomavirus types: Phylogenetic and medical implications. Internat. J. Cancer, 118, 1071-1076 (2006).
Calleja-Macias, I.E., Kalantari, M., Villa, L.L., Prado, J.C., Allan, B., Williamson, A.L., Chung, L.P., Collins, R.C., Zuna, R. E.,, Dunn, S.T., Chu, T.Y., Cubie, H.A., Cuschieri, K., von Knebel-Doeberitz, M., Martins, C.R., Sanchez, G.I., Bosch, F.X., Munoz, N., Bernard, H.U. Worldwide genomic diversity of the high-risk human papillomaviruses-31, 35, 52, and 58, which are closely related to HPV-16. J. Virol. 79, 13630-13640 (2005).
Wiley, D.J., Huh, J., Chang, C., Kalantari, M., Rao, J.Y., Goetz, M., Msongsong, E., Poulter, M., Bernard, H.U. Methylation of human papillomavirus DNA in samples of HIV-1 infected men screened for anal cancer. J. Acqu. Immunodef. Syndr. 39, 143-151 (2005).
Calleja-Macias, I.E., Kalantari, M., Huh, J., Ortiz-Lopez, R., Rojas-Martines, A., Gonzales-Guerrero, J.F., Williamson, A.L., Hagmar, B., Wiley, D.J., Villarreal, L., Bernard, H.U., Barrera-Saldana, H.A. High prevalence of specific variants of human papillomavirus-16, 18, 31, and 35 in a Mexican population. Virology, 319, 315-323 (2004).
Kalantari, M., Calleja-Macias, I.E., Tewari, D., Hagmar, B., Barrera-Saldana, H.A, Wiley, D.J., Bernard, H.U. Conserved methylation patterns of human papillomavirus-16 DNA in asymptomatic infection and cervical neoplasia. J. Virol. 78, 12762-12772 (2004).
Bernard, H.U. Gene Expression of Genital Human Papillomaviruses and Potential Antiviral Approaches. Antiviral Therapy 7, 219-237 (2002).
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