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Paul F. Lambert, Ph.D.

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Paul Lambert Photo Howard M. Temin Professor of Oncology

B.S., 1979, Biochemistry, University of Massachusetts, Amherst
Ph.D., 1985, Biochemistry, University of Wisconsin-Madison
Postdoctoral research: Laboratory of Peter Howley, National Cancer Institute

Office: 220A McArdle Laboratory
Telephone:
Office - (608) 262-8533; Lab - (608) 262-6407
Email: lambert@oncology.wisc.edu

Lab Home Page

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Research Interests: Molecular genetics of papillomaviruses

Research Description: Our lab’s research is focused on understanding the role of human papillomavirus (HPV) in cancer.  HPVs cause 5% of all human cancers. These include cervical cancer, other anogenital cancers and a growing proportion of head and neck cancers.  Through the use of genetically engineered mice (GEM) we have developed models for HPV-associated cervical, anal and head/neck carcinogenesis, defined the individual roles of viral oncogenes in carcinogenesis in these organs, identified the mechanisms of action by which these oncogenes contribute to carcinogenesis, defined their temporal role in carcinogenesis, and defined the roles of estrogen and its receptor in cervical carcinogenesis and the utility of estrogen receptor antagonists in treating and preventing cervical cancer.  Major current directions in the lab that make continued use of the GEM models include understanding the interplay between viral oncogenes and cellular signaling and DNA damage response pathways in causing cancer, and the influences of viral genes on epigenetic regulation and epithelial stem cell biology.

In recent years we have complemented our use of GEM models with the development patient derived xenografts (PDX) models in which human cancers are directly grafted and passaged in immune-deficient mice. PDX models provide us the ability to test new therapeutic approaches for treating human cancers that we have identified through our studies using the GEM models. For example, using our GEM model for HPV-associated anal cancer, we identified that the cellular mTOR pathway is activated, and its inhibition by rapamycin suppresses anal cancer growth.  We then demonstrated the therapeutic value of rapamycin in treating human anal cancer using the first human anal cancer PDX model. Likewise, working with our clinical colleagues we have now established an array of PDX models for both HPV-positive and HPV-negative human head and neck cancers that will be used alongside our GEM models for these cancers to define novel therapeutic approaches for treating these cancers.

The papillomaviral life cycle is intricately tied to the differentiation of the host epithelium it infects.  Using artificial skin cultures wherein we can recapitulate all the stages of the viral life cycle in differentiating epithelium, we continue our efforts to dissect the role of viral genes and cellular pathways in the viral life cycle.  Recently, we established a mouse papillomavirus infection model in laboratory mice.  This new model will allow us to use the power of mouse genetics to better understand virus-host interactions involved in infection and possibly also virally-induced cancers.

Selected recent publications

Adams, A. K., Hallenbeck, G. E., Casper, K. A., Patil, Y. J., Wilson, K. M., Kimple, R. J., Lambert, P. F., Witte, D. P., Xiao, W., Gillison, M. L., Wikenheiser-Brokamp, K. A., Wise-Draper, T. M., and Wells, S. I.  DEK Promotes HPV-Positive and –Negative Head and Neck Cancer Cell Proliferation.  Oncogene, in press, 2014 [Epub ahead of print Mar 10 2014].

Park, J. W., Shin, M.-K., and Lambert, P. F.  High Incidence of Female Reproductive Tract Cancers in FA-Deficient HPV16-Transgenic Mice Correlates with E7’s Induction of DNA Damage Response, an Activity Mediated by E7’s Inactivation of Pocket Proteins.  Oncogene, in press, 2014 [Epub ahead of print Sep 9 2013].

Son, J., Park, J. W., Lambert, P. F., and Chung, S.-H.  Requirement of Estrogen Receptor Alpha DNA-Binding Domain for HPV Oncogene-Induced Cervical Carcinogenesis in Mice.  Carcinogenesis, 35(2):  489-496, 2014.

Spurgeon, M. E., Chung, S.-H., and Lambert, P. F.  Recurrence of Cervical Cancer in Mice After Selective Estrogen Receptor Modulator Therapy.  Am. J. Pathol., 184(2):  530-540, 2014.

Stein, A. P., Saha, S., Yu, M., Kimple, R. J., and Lambert, P. F.  Prevalence of Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma in the United States Across Time.  Chem. Res. Toxicol., in press, 2014 [Epub ahead of print Apr 2 2014].

Choyce, A., Yong, M., Narayan, S., Mattarollo, S. R., Liem, A., Lambert, P. F., Frazer, I. H., and Leggatt, G. R.  Expression of a Single, Viral Oncoprotein in Skin Epithelium Is Sufficient to Recruit Lymphocytes.  PLoS One, 8(2):e57798, 2013.

Chung, S.-H., Shin, M. K., Korach, K. S., and Lambert, P. F.  Requirement for Stromal Estrogen Receptor Alpha in Cervical Neoplasia.  Horm. Cancer, 4(1): 50-59, 2013.

Cortés-Malagón, E. M., Bonilla-Delgado, J., Díaz-Chávez, J., Hidalgo-Miranda, A., Romero-Cordoba, S., Üren, A., Çelik, H., McCormick, M., Munguía-Moreno, J. A., Ibarra-Sierra, E., Escobar-Herrera, J., Lambert, P. F., Mendoza-Villanueva, D., Bermudez-Cruz, R. M., and Gariglio, P.  Gene Expression Profile Regulated by the HPV16 E7 Oncoprotein and Estradiol in Cervical Tissue.  Virology, 447(1-2):  155-165, 2013.

Hernández-Monge, J., Garay, E., Raya-Sandino, A., Vargas-Sierra, O., Díaz-Chávez, J., Popoca-Cuaya, M., Lambert, P. F., González-Mariscal, L., and Gariglio, P.  Papillomavirus E6 Oncoprotein Up-Regulates Occludin and Z0-2 Expression in Ovariectomized Mice Epidermis.  Exp. Cell Res., 319(17):  2588-2603, 2013.

Johannsen, E., and Lambert, P. F.  Epigenetics of Human Papillomaviruses.  Virology, 445(1-2): 205-212, 2013.

Kimple, R. J., Harari, P. M., Torres, A. D., Yang, R. Z., Soriano, B. J., Yu, M., Armstrong, E. A., Blitzer, G. C., Smith, M. A., Lorenz, L. D., Lee, D., Yang, D. T., McCulloch, T. M., Hartig, G. K., and Lambert, P. F.  Development and Characterization of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinoma Tumorgrafts.  Clin. Cancer Res., 19(4): 855-864, 2013.

Kimple, R. J., Smith, M. A., Blitzer, G. C., Torres, A. D., Martin, J. A., Yang, R. Z., Peet, C. R., Lorenz, L. D., Nickel, K. P., Klingelhutz, A. J., Lambert, P. F., and Harari, P. M.  Enhanced Radiation Sensitivity in HPV-Positive Head and Neck Cancer.  Cancer Res., 73(15): 4791-4800, 2013.

Lambert, P. F., McBride, A., and Ulrich Bernard, H.  The Papillomavirus Episteme.  Virology (Special Issue), 445(1-2): 1, 2013.

Lorenz, L. D., Rivera Cardona, J., and Lambert, P. F.  Inactivation of p53 Rescues the Maintenance of High Risk HPV DNA Genomes Deficient in Expression of E6.  PLoS Pathog., 9(10): e1003717, 2013.

McNairn, A. J., Doucet, Y., Demaude, J., Brusadelli, M., Gordon, C. B., Uribe-Rivera, A., Lambert, P. F., Bouez, C., Breton, L., and Guasch, G.  TGFβ Signaling Regulates Lipogenesis in Human Sebaceous Glands Cells.  BMC Dermatol., 13(1): 2, 2013.

Michael, S., Lambert, P. F., and Strati, K.  The HPV16 Oncogenes Cause Aberrant Stem Cell Mobilization.  Virology, 443(2): 218-225, 2013.

Park, J. W., Shin, M.-K., Pitot, H. C., and Lambert, P. F.  High Incidence of HPV-Associated Head and Neck Cancers in FA Deficient Mice Is Associated with E7’s Induction of DNA Damage through Its Inactivation of Pocket Proteins.  PLoS One, 8(9):e75056, 2013.

Rivera, C., Simonson, S. J., S., Yamben, I. F., Shatadal, S., Nguyen, M. M., Beurg, M., Lambert, P. F., and Griep, A. E.  Requirement for Dlgh-1 in Planar Cell Polarity and Skeletogenesis during Vertebrate Development.  PLoS One, 8(1):e54410, 2013.

Spurgeon, M. E., and Lambert, P. F.  Merkel Cell Polyomavirus:  A Newly Discovered Human Virus with Oncogenic Potential.  Virology, 435(1):  118-130, 2013.

Bonilla-Delgado, J., Bulut, G., Liu, X., Cortés-Malagón, E. M., Schlegel, R., Flores-Maldonado, C., Contreras, R. G., Chung, S.-H., Lambert, P. F., Üren, A., and Gariglio, P.  The E6 Oncoprotein from HPV16 Enhances the Canonical Wnt/β-Catenin Pathway in Skin Epidermis in Vivo.  Mol. Cancer Res., 10: 250-258, 2012.

Hoskins, E. E., Morreale, R. J., Werner, S. P., Higginbotham, J. M., Laimins, L. A., Lambert, P. F., Brown, D. R., Gillison, M. L., Nuovo, G. J., Witte, D. P., Kim, M.-O., Davies, S. M., Mehta, P. A., Kovacic, M. B., Wikenheiser-Brokamp, K. A., and Wells, S. I.  The Fanconi Anemia Pathway Limits Human Papillomavirus Replication.  J. Virol., 86: 8131-8138, 2012.

Huang, H.-S., and Lambert, P. F.  Use of an in Vivo Animal Model for Assessing the Role of Integrin α6β4 and Syndecan-1 in Early Steps in Papillomavirus Infection.  Virology, 433: 395-400, 2012.

Huang, H.-S., Pyeon, D., Pearce, S. M., Lank, S. M., Griffin, L. M., Ahlquist, P., and Lambert, P. F.  Novel Antivirals Inhibit Early Steps in HPV Infection.  Antiviral Res., 93:  280-287, 2012.

Ibarra Sierra, E., Díaz Chávez, J., Cortés-Malagón, E. M., Uribe-Figueroa, L., Hidalgo-Miranda, A., Lambert, P. F., and Gariglio, P.  Differential Gene Expression between Skin and Cervix Induced by the E7 Oncoprotein in a Transgenic Mouse Model.  Virology, 433: 337-345, 2012.

Jabbar, S. F., Park, S., Schweizer, J., Berard-Bergery, M., Pitot, H. C., Lee, D., and Lambert, P. F.  Cervical Cancers Require the Continuous Expression of the Human Papillomavirus Type 16 E7 Oncoprotein Even in the Presence of the Viral E6 Oncoprotein.  Cancer Res., 72: 4008-4016, 2012.

Shin, M.-K., Pitot, H. C., and Lambert, P. F.  Pocket Proteins Suppress Head and Neck Cancer.  Cancer Res., 72: 1280-1289, 2012.

Shin, M.-K., Sage, J., and Lambert, P. F.  Inactivating All Three Rb Family Pocket Proteins Is Insufficient to Initiate Cervical Cancer.  Cancer Res., 72: 5418-5427, 2012. 

Togtema, M., Pichardo, S., Jackson, R., Lambert, P. F., Curiel, L., and Zehbe, I.  Sonoporation Delivery of Monoclonal Antibodies against Human Papillomavirus 16 E6 Restores p53 Expression in Transformed Cervical Keratinocytes.  PLoS One, 7(11):e50730, 2012.

Wen, Z., Pyeon, D., Wang, Y., Lambert, P., Xu, W., and Ahlquist, P.  Orphan Nuclear Receptor PNR/NR2E3 Stimulates p53 Functions by Enhancing p53 Acetylation.  Mol. Cell. Biol., 32:  26-35, 2012.

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