Find a Health Care Professional / Researcher

Susanne Wells, PhD

Appointment

Associate Professor of Pediatrics

Email

susanne.wells@cchmc.org

Phone

513-636-5986

Fax

513-636-3549

Bio

Dr. Wells graduated from the University of Konstanz, Germany, with a degree in Biology. She completed her PhD in Molecular Biology at the State University of Stony Brook, NY, and her Postdoctoral Fellowship at Harvard Medical School, MA. Dr. Wells moved to Cincinnati Children's Hospital Medical Center in 2002 to study human papillomavirus infection and associated carcinogenesis.

Credentials

BS: Biology, University of Konstanz, Germany, 1992
PhD: Molecular Genetics, State University of Stony Brook, NY, 1997
Postdoctoral Fellowship: Molecular Virology, Harvard Medical School, Boston, MA

Awards and Honors

2008 Session Chair, International DNA Tumor Virus Conference, Madison, WI
2007 Schmidlapp Lecture Award, Cincinnati Children’s Hospital Medical Center
2006 Session Chair, International DNA Tumor Virus Conference, San Diego, CA
2004 American Cancer Society Board Member, Hamilton Branch
2004 American Cancer Society Study Section member, Ohio Division
2003 Trustee Award, Cincinnati Children’s Hospital Research Foundation
2000 NRSA Postdoctoral Fellowship (not elected due to other funding)
2000 The Medical Foundation Postdoctoral Fellowship ($60,000)
1999 Taplin Research Postdoctoral Fellowship ($24,000)
1997 US provisional patent application 60/088,321. Co-inventor with Patrick Hearing. Specific repression of adenovirus packaging

Research

Visit the Wells Lab Site

Squamous cell carcinoma (SCC) is the second most common form of skin cancer, with over 250,000 new cases per year estimated in the United States. Infection with the human papillomaviruses (HPVs) and expression of the two viral oncogenes E6 and E7 is one well defined cause. The high-risk HPV types cause anogenital malignancies such as cervical cancer and a substantial proportion of head and neck cancers. FDA approval of the HPV vaccine Gardasil is expected to reduce disease burden in the future, but its high cost, dosing regimen and the lack of protection for individuals that are already infected pose major obstacles to the field. Therapeutic vaccines and effective antivirals are not yet available. The goal of our studies is to advance our understanding of both HPV-related and –unrelated SCC development, and to develop new approaches to the diagnosis and treatment of HPV as a major cause of cancer worldwide. Two major areas of investigation in the laboratory focus on 1) mechanisms by which the HPV oncogenes subvert the host cell machinery to promote abnormal cell growth and cancer, and 2) the role of specific cellular HPV targets in viral replication and cellular transformation. Model systems utilized include primary human and murine cells and tumors, three-dimensional organotypic epithelial rafts and mouse models of cancer.

Functions of the human DEK proto-oncogene

The human DEK protein is frequently upregulated in aggressive human tumors such as glioblastoma, melanoma, and bladder cancer. A number of DEK functions have been described in vitro and include DNA supercoiling and possible roles in DNA replication, transcription and splicing. We have demonstrated that DEK suppresses senescence, apoptosis and differentiation in different model systems, thus promoting cellular growth and survival. Furthermore, DEK exhibits oncogenic functions in 3D models of cancer: First, DEK overexpression in human keratinocytes caused hyperplasia in organotypic epithelial rafts, with inappropriate cell cycle progression and expansion of the p63- positive stem and progenitor cell compartment. Second, DEK cooperated with known oncogenes for increased squamous cell tumor formation in immunodeficient mice. Third, DEK knockout mice were partially resistant to chemically induced skin tumorigenesis. Our studies are the first to define DEK as a bona fide oncogene, and current projects are focused on defining the underlying mechanisms of DEK function as an oncogene and to interfere with DEK activities for the development of novel cancer therapies.

The role of HPV in Fanconi anemia.

Fanconi anemia (FA) is a rare primarily autosomal recessive genome instability syndrome where patients are at a dramatically elevated risk of squamous cell carcinoma (SCC) of the head and neck and anogenital tract. Tumors appear early in life, and progress with striking aggressiveness. Conventional clastogenic therapies such as radiation and chemotherapy are often toxic because of the patients’ DNA damage response defects. Development of alternative treatments has been severely limited by the lack of availability of human models of FA SCC. The FA Comprehensive Care Center at CCHMC has offered a unique opportunity for translational studies, and resulting patient-derived 3D SCC models will be exploited to facilitate screens for new therapies, and support preclinical trials for new treatments. Our recent data demonstrate that loss of function of the FA pathway in high risk HPV16 positive keratinocytes stimulates viral and cellular replication in vitro, and malignant transformation in vivo. Based on these findings, we hypothesize that FA genes are modifiers of HPV infection. Experiments to determine the clinical and molecular importance of FA-HPV crosstalk are currently ongoing.

Research Grants and Contracts

Translational Research Initiative Grant, CCHMC, July 2009-June 2010
FA-controlled HPV transformation

Fanconi Anemia Research Fund Grant, March 2009-February 2011
HPV Replication and Transformation in FA Squamous Cell Carcinomas

NIH RO1 CA116316-01, April 2006-March 2011
Role and regulation of the human DEK proto-oncogene

Publications, Most Recent

Connect to Susanne Wells' publications on PubMed

Wise-Draper TM, Wells SI (2008). Papillomavirus E6 and E7 proteins and their cellular targets. Front Biosci., 13, 1003-1017.

Hoskins EE, Gunawardena RW, Habash B, Wise-Draper TM, Jansen M, Knudsen E, Wells SI (2008). Coordinate regulation of Fanconi anemia gene expression occurs through the Rb/E2F pathway. Oncogene, 27, 4798-4808.

Spardy N, Duensing A, Hoskins EE, Wells SI, Duensing S (2008). HPV-16 E7 reveals a link between DNA replication stress, FANCD2 and alternative lengthening of telomeres (ALT)-associated PML bodies (APBs). Cancer Research, 68, 9954-9963.

Bourgo RJ, Braden WA, Wells SI, Knudsen ES (2009). Activation of the retinoblastoma tumor suppressor mediates cell cycle inhibition and cell death in specific cervical cancer cell lines.Mol. Carcinogenesis, 48, 45-55.

Wise-Draper TM, Morreale RJ, Morris TA, Mintz-Cole RA, Hoskins EE, Balsitis SJ, Husseinzadeh N, Witte DP, Wikenheiser-Brokamp KA, Lambert PF, Wells SI (2009). DEK proto-oncogene expression interferes with the normal epithelial differentiation program. American Journal of Pathology, 174, 71-81.

Hoskins EE, Morris TA, Higginbotham JM, Spardy N, Cha E, Kelly P, Williams DA, Wikenheiser-Brokamp KA, Duensing S, Wells SI (2009). Fanconi anemia deficiency stimulates HPV-associated hyperplastic growth in organotypic epithelial raft culture.Oncogene, 28, 674-85.

Wise-Draper TM, Mintz-Cole RA, Morris TA, Simpson DS, Wikenheiser-Brokamp KA, Currier MA, Cripe TP, Grosveld GC, Wells SI (2009). Overexpression of the cellular DEK protein promotes epithelial transformation in vitro and in vivo.Cancer Research, 69, 1792-1799

Morreale RJ., Kahn JA, Butsch Kovacic M, Hegde RS, Aronow BJ, Wells SI (2009). Insights from the transcriptional profiling of human papillomavirus infection and associated carcinogenesis. Molecular Biology of DNA Tumor Virus Gene Products. K. Yoshida (ed). In press: Research Signpost Company.

Wise-Draper TM, Wells SI (2008).Papillomavirus E6 and E7 proteins and their cellular targets. Front Biosci., 13, 1003-1017.

Jones EE, Wells SI (2006). Cervical cancer and human papillomaviruses: inactivation of retinoblastoma and other tumor suppressor pathways.Curr Mol Med., 6(7), 795-808.

Presentations, Most Recent:

2009. International DNA Tumor Virus Meeting, Oxford, UK. G. Kavanaugh, T. Wise-Draper, L. Lu, J. Bissler, R. Drissi, P. Andreassen and S. I. Wells. Uncovering DEK’s role in DNA damage response.

2009. International DNA Tumor Virus Meeting, Oxford, UK. E. Hoskins, J. Higginbotham, K. Wikenheiser-Brokamp and S. I. Wells. FA loss stimulates HPV transformation.

2009. The Ohio State University Comprehensive Cancer Center 11th Annual Meeting. M. Morrison and S.I. Wells. HPV E2 induced senescence stimulates migration in HPV positive cervical cancer cells.

2009. The Ohio State University Comprehensive Cancer Center 11th Annual Meeting. L. M. Privette-Vinnedge, K. A. Wikenheiser-Brokamp, and S.I. Wells. The role of the DEK proto-oncogene in hormone receptor positive breast cancers.

2008. Twentieth Annual Fanconi Anemia Research Fund Scientific Symposium. Eugene, OR. Suppression of HPV associated hyperplasia by FA complementation of keratinocytes from children with Fanconi Anemia. E. E. Hoskins, T. A. Morris, J. M. Higginbotham, N. Spardy, E. Cha, P. Kelly, D. A. Williams, K. A. Wikenheiser-Brokamp, S. Duensing and S. I. Wells.

2008. Suppression of DNA damage defects and HPV-associated hyperplasia by correction of FANCA deficiency in keratinocytes from children with Fanconi Anemia. Elizabeth E. Hoskins, Teresa A. Morris, Jennifer M. Higginbotham, Nicole Spardy, Elliot Cha, Patrick Kelly, David A. Williams, Kathryn A. Wikenheiser-Brokamp, Stefan Duensing and Susanne I. Wells.

2008. International DNA Tumor Virus Meeting. Madison, WI. DEK proto-oncogene depletion results in DNA damage and S phase progression defects. Gina M. Kavanaugh, Trisha M. Wise-Draper, Monique A. Morrison, Lu Lu, Paul R. Andreassen, John J. Bissler, James M. Wells, Gerard C. Grosveld and Susanne I. Wells.

2008. International DNA Tumor Virus Meeting. Madison, WI. E2-induced HeLa cell senescence stimulates migration. Monique A. Morrison, Matthew Kofron, Marie-Dominique Filippi, Yi Zheng and Susanne I. Wells.

2007. Nineteenth Annual Fanconi Anemia Research Fund Scientific Symposium. Chicago, IL, USA. The high risk HPV E7 protein mediates coordinate regulation of Fanconi anemia genes through the Rb/E2F pathway. Elizabeth E. Jones, Kristen B. Habash, Trisha M. Wise-Draper, Michael Jansen, Patrick Kelly, David A. Williams, Erik S. Knudsen and Susanne I. Wells

2007. International ICGEB DNA Tumor Virus Meeting. Trieste, Italy. The human DEK proto-oncogene is involved in DNA damage response pathways. Trisha M. Wise-Draper, Paul R. Andreassen and Susanne I. Wells

2006. International DNA Tumor Virus Meeting, San Diego, CA, USA. Apoptosis inhibition by the human DEK oncoprotein involves p53. Trisha M. Wise-Draper, Hillary V. Allen, Elizabeth E. Jones, Kristen B. Habash, Hiroshi Matsuo, and Susanne I. Wells

2006. International DNA Tumor Virus Meeting, San Diego, CA, USA. Molecular cross-talk between HPV and Fanconi Anemia pathways. Elizabeth E. Jones, Kristen B. Habash, Paul R. Andreassen and Susanne I. Wells