) As a student in an M.D.-Ph.D. program at Albert Einstein College of Medicine, Dr. Nakagawa studied the structure function relationships of murine Major Histocompatibility Complex in terms of its immunological and physiological properties. After completing a residency program in laboratory medicine at the University of California at San Francisco, where she still is, she began a research project studying cell-mediated immunity to Human Papilloma Virus type 16 (HPV 16) which is a causative agent of cervical dysplasia and cancer. Data collected thus far, using a T cell proliferative assay as well as a cytotoxic lymphocyte assay, support her working hypothesis that cell-mediated immunity to HPV is instrumental in its elimination and thus is protected against the development of associated diseases. The experiments proposed in this application are nested with an ongoing longitudinal study in which HPV 16 infected women who have not developed high grade intraepithelial lesions are tested for cytotoxic T lymphocyte responses to HPV 16 oncogenic proteins, E6 and E7.
The specific aims of this project are to characterize the lymphocyte subset(s) responsible for anti-HPV activity, to eliminate background activity, to explore alternative methods of in vitro stimulation, and to develop a protocol to perform cytotoxic T lymphocyte assay using T cell lines instead of bulk cultures. The last aim will give us a tool to identify immunodominant epitopes of HPV 16 in the future. The long-term goal of this project is to develop effective vaccines and immunotherapy for prevention and treatment of cervical cancer. Dr. Nakagawa's long-term career goal is to continue research in HPV immunology as an independent investigator. She envisions this will be best accomplished by becoming a faculty member at an academic medical center where she will also have clinical responsibilities as a laboratory medicine physician. The University of California at San Francisco, which is a major academic medical institution with many distinguished scientists, offers an excellent environment to develop skills and further her expertise in the field to accomplish her goals.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
1K07CA075974-01
Application #
2440237
Study Section
Subcommittee G - Education (NCI)
Program Officer
Agelli, Maria
Project Start
1998-02-01
Project End
2003-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Farhat, Sepideh; Nakagawa, Mayumi; Moscicki, Anna-Barbara (2009) Cell-mediated immune responses to human papillomavirus 16 E6 and E7 antigens as measured by interferon gamma enzyme-linked immunospot in women with cleared or persistent human papillomavirus infection. Int J Gynecol Cancer 19:508-12
Nakagawa, Mayumi; Kim, Kevin H; Gillam, Tiffany M et al. (2007) HLA class I binding promiscuity of the CD8 T-cell epitopes of human papillomavirus type 16 E6 protein. J Virol 81:1412-23
Nakagawa, Mayumi; Kim, Kevin H; Moscicki, Anna-Barbara (2004) Different methods of identifying new antigenic epitopes of human papillomavirus type 16 E6 and E7 proteins. Clin Diagn Lab Immunol 11:889-96
Nakagawa, Mayumi; Viscidi, Raphael; Deshmukh, Ian et al. (2002) Time course of humoral and cell-mediated immune responses to human papillomavirus type 16 in infected women. Clin Diagn Lab Immunol 9:877-82
Scott, M; Nakagawa, M; Moscicki, A B (2001) Cell-mediated immune response to human papillomavirus infection. Clin Diagn Lab Immunol 8:209-20
Nakagawa, M; Stites, D P; Patel, S et al. (2000) Persistence of human papillomavirus type 16 infection is associated with lack of cytotoxic T lymphocyte response to the E6 antigens. J Infect Dis 182:595-8
Nakagawa, M; Stites, D P; Palefsky, J M et al. (1999) CD4-positive and CD8-positive cytotoxic T lymphocytes contribute to human papillomavirus type 16 E6 and E7 responses. Clin Diagn Lab Immunol 6:494-8