Denise A. Galloway

Appointments and Affiliations

Fred Hutchinson Cancer Research Center
Associate Director, Human Biology Division
Member, Human Biology and Public Health Sciences
University of Washington
School of Medicine
Microbiology
Research Professor
Professional Headshot of NAME

Mailing Address

Fred Hutchinson Cancer Research Center
C1-015
1100 Fairview Ave. N.
Seattle, Washington 98109
United States

Contact

Phone: (206) 667-4500
Fax: (206) 667-5815
dgallowa@fhcrc.org
http://labs.fhcrc.org/galloway/index.html

Degrees

Post-doctoral, Cold Spring Harbor Laboratory, Tumor Virology, 1978.
Ph.D., The City University of New York, Biological Sciences, 1975.

Research Interests

The overall focus of the Galloway Lab is to understand the mechanisms by which viruses, particularly human papillomaviruses (HPV) and human polyomaviruses (HPyV), contribute to the development of cancers. Much of our research has focused on the high risk HPVs (HR-HPVs) that are causally associated with all cervical cancers and the majority of anogenital and oropharyngeal cancers. Additionally, we have been investigating whether genus beta HPVs are involved in squamous cell skin cancers. Most recently we are studying the role that the Merkel Cell Polyomavirus (MCPyV) plays in Merkel Cell Carcinoma. A future goal is to look for novel virus-cancer associations.

A major part of our lab's effort is to understand the mechanism by which HR-HPV E6 and E7 contribute to the neoplastic process. We have shown that E6 induces transcription of the catalytic subunit of telomerase, hTERT. We identified a novel E6/E6AP partner, NFX1 that modulates TERT transcription. NFX1 has two isoforms: NFX1-91 binds to a X-box motif adjacent to the proximal E box and represses transcription. NFX1-123 functions post-transcriptionally to regulate hTERT mRNA stability in association with poly-A binding proteins. We are currently investigating how activation of hTERT may contribute to the HPV lifecycle.

A longstanding interest has been in characterizing the humoral immune response to HPV following natural infection or vaccination. We have mapped epitopes involved in virus neutralization and continue to characterize the breadth of the antibody response. New studies are characterizing the breadth of the B-cell response with the goal of understanding long-term protection. We are using HPV virus-like particles (VLPs) to isolate virus specific memory B cells and to clone their antibody genes.

We have become interested in whether another branch of the HPV family, the beta HPVs play a role in squamous cell skin cancer (SCSC). In collaboration with epidemiologists and clinicians we are involved in studying beta HPV infection in organ transplant recipients who are at greatly increased risk of developing SCSC. To better understand how the beta HPVs might contribute to skin carcinogenesis we are studying the role of the b-HPV E6/E7 proteins in blocking apoptosis, blunting the response to UV damage and altering differentiation through perturbing the stability of the p300 transcriptional repressor.

Our interest in skin cancer led us to study a new virus: cancer association between the Merkel cell polyomavirus (MCPyV) and Merkel Cell carcinoma (MCC). We have surveyed the seroprevalence of MCPyV and have showed that antibodies to the viral T antigen can be used as a prognostic marker of disease recurrence. Unlike the HR-HPV E6/E7 oncoproteins the T antigens of MCPyV do not immortalize or transform cells in culture.

The virus-like particles (VLPs) of HPV have proven to be extremely effective as prophylactic vaccines to prevent HPV-associated diseases. We wondered whether a similar strategy could be used to develop vaccines for enterovirus 71 (EV71), a picornavirus that is associated with neurologic complications of hand, foot and mouth disease (HFMD) in young children. We have generated VLPs with the four capsid proteins of EV71 and will be testing their immunogenicity and ability to protect in a challenge model with newborn mice.

Honors and Awards

2011, Team Science Award, American Association for Cancer Research, Seattle HPV Team
2008, Fellow, American Association for the Advancement of Science
2000, MERIT Award, National Institutes of Health
1994, Fellow, American Academy of Microbiology
1989, Fellow, Infectious Diseases Society of America

Recent Publications

2014
2013
2012
2011
Burnett-Hartman, AN, Newcomb PA, Mandelson MT, Galloway DA, Madeleine MM, Wurscher MA, Carter JJ, Makar KW, Potter JD, Schwartz SM.  2011.  No Evidence for Human Papillomavirus in the Etiology of Colorectal Polyps.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 20(10):2288-97. Abstract
Iyer, JG, Afanasiev OK, McClurkan C, Paulson K, Nagase K, Jing L, Marshak JO, Dong L, Carter J, Lai I et al..  2011.  Merkel Cell Polyomavirus-Specific CD8+ and CD4+ T-cell Responses Identified in Merkel Cell Carcinomas and Blood.. Clinical cancer research : an official journal of the American Association for Cancer Research. 317(21):6671-6680. Abstract
Johnson, LG, Schwartz SM, Malkki M, Du Q, Petersdorf EW, Galloway DA, Madeleine MM.  2011.  Risk of cervical cancer associated with allergies and polymorphisms in genes in the chromosome 5 cytokine cluster.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 20(1):199-207. Abstract
2010
2009