Peter M. Howley, M.D.
Shattuck Professor of Pathological Anatomy
Head of the Department of Pathology
Harvard Medical School
New Research Building, 9th floor
77 Avenue Louis Pasteur
Tel: 617-432-2884
Fax: 617-432-2882
e-mail:phowley@hms.harvard.edu
5 postdoctoral fellows, 2 graduate students
The Howley laboratory studies the molecular biology of the papillomaviruses using the bovine papillomavirus (BPV) as well as the human papillomaviruses (HPVs). Projects in the laboratory involve the viral E2 protein and its roles in the regulation of viral transcription, DNA replication and genome maintenance. There are over 100 different HPVs, and some of them are associated with specific human cancers most notably human cervical cancer. We study the role of these HPVs in human neoplasia and the mechanisms by which they contribute to cellular transformation. The cancer associated HPVs encode two oncoproteins, E6 and E7, that have oncogenic properties that contribute directly to HPV associated carcinogenesis. A major focus of the laboratory is the study of E6 oncoprotein which has multiple functions, including the ability to functionally inactivate p53 by targeting its ubiquitylation and proteolysis. This process is mediated by a cellular protein, E6AP, that binds to E6 and functions as an E3 ubiquitin protein ligase in promoting the E6 dependent ubiquitylation of p53. Our work with the E6 mediated ubiquitylation of p53 has led us to ask fundamental questions about the ubiquitylation and protein degradation pathways. An additional area of study in the laboratory involves the BPV E7 protein that transforms cells in an RB independent manner. Another major area of interest in the laboratory involves the viral E2 regulatory protein that is involved in viral transcription, viral DNA replication and viral genome maintenance in dividing cells. Rotation projects are available in each of these areas.
References:
- You, J. Croyle, J.L., Nishimura, A., Ozato, K. and Howley, P.M. Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell, 117:349-360, 2004.
- DeMasi, J., Huh, K.-W., Nakatani, Y., Münger, K., and Howley, P.M., Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding. Proc. Nat. Acad. Sci. USA, 102:11486-11491, 2005.
- You, J. Schweiger, M.-R., and Howley, P.M.,Inhibition of E2 binding to Brd4 enhances viral genome loss and phenotypic reversion of bovine papillomavirus transformed cells. J. Virol. 79:14956-14961, 2005.
- Schweiger, M.-R., You, J.,, and Howley, P.M. Brd4 mediates papillomavirus E2 transactivation function. J. Virol. 80:4276-4285, 2006.
- DeMasi, J. Chao, M.C., Kumar, A.S., and Howley, P.M. Bovine papillomavirus E7 oncoprotein inhibits anoikis. J. Virol. 81, 9419-9425, 2007.
- Schweiger, M.-R., Ottinger, M., You, J., and Howley, P.M. Brd4 independent transcriptional repression function of the papillomavirus E2 proteins. J. Virol. 81:9612-9622, 2007.
Immunology webpage updated 12/02/2009