Cheryl A. Winkler
*IRSP SAIC-Frederick, MD 21702 #Laboratory of Genomic Diversity, NCI-Frederick, MD 21702
(Tel: 301-846-5747 Fax: 301-846-6327 Email: winkler@mail.ncifcrf.gov)
The progression to immunodeficiency and HIV-related diseases is a dynamic process involving the inte.raction between viral and host gene products. The host functions may be potential rate limiting steps for HIV cell entry, replication, and pathogenesis. Modification of these functions by endemic mutations or promoter variants may influence HIV-1 infection, CD4+ cell depletion, immune response, and specific AIDS outcomes including the AIDS-related outcomes Kaposi's sarcoma and lymphoma. To date analysis of allele and genotype frequency distributions in clinically defined HIV/AIDS cohorts have shown the influence of 11 separate genes on the outcome of HIV-1 exposure. The genes include: CCR5, CCR5P, CCR2, SDF1, IL1O, IL4, MBL, H~-A, HLA-B, HLA-C, and RANTES. These studies indicate that common alleles at multiple loci contribute to HIV infection/pathogenesis and have implication for therapy by identifying potential targets for intervention. Funded in part from NCI, NIH Contract #NO 1-CO-56000
References:
(1) Dean, M., Carrington, M., Winkler, C., Huttley, G.A., Smith, M.W., Allikmets, R., Goedert, J., Buchbinder, S.P., Vittinghoff, E., Gomperts, E., Donfield, S., Vlahov, D., Kaslow, R., Saah, A., Rinaldo, C., Detels, R., Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, San Francisco City Cohort, ALIVE Study, and O'Brien, S. J.: Genetic restriction of HIV- 1 infection and progression to AIDS by a deletion allele of the CKR5 Structural Gene. Science 273: 1856-1862, 1996.
(2) Smith, M.W., Dean, M., Carrington, M., Winkler, C., Huttley, G.A., Lomb, D.A., Goedert, J.J., O'Brien, T.R., Jacobson, L.P., Kaslow, R., Buchbinder, S., Vittinghoff, E., Vlahov, D., Hoots, K., Hilgartner, M.W., Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study, and O'Brien, S. J.: Contrasting genetic influence of CCR2 and CCR5 receptor gene variants on HIV- 1 infection and disease progression. Science 277: 959-965, 1997.
(3) Winkler, C., Modi, W., Smith, M.W., Nelson, G.W., Wu, X., Carrington, M., Dean, M., Honjo, T., Tashiro, K., Yabe, D., Buchbinder, S., Vittinghoff, E., Goedert, J.J., O'Brien, T. R., Jacobson, L.P., Detels, R., Donfield, S., Willoughby, A., Gomperts, E., Vlahov, D., Phair, J., ALIVE, HGDS, MACS, MHCS, SFCC, and O'Brien, S. J.: Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. Science 279: 389-393, 1997.
(4) Hendel, H., Caillat-Zucman, S., Lebuanec, H., Carrington, M., O'Brien, S., Andrieu, J.M., Schachter, F., Zagury, D., Rappaport, J., Winkler, C., Nelson, G.W., and Zagury, J.F.: New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS. J. Immunol. 162: 6942-6946, 1999.
(5) Daar, E., Lynn, H., Donfield, S., Gomperts, E., Hilgartner, M.W., Hoots, K., Chernoff, D., Winkler, C., and O'Brien, S. J.: The effects of plasma HIV RNA, CD4+ T-lymphocytes and the chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. J. Acquir. Immune. Defic. Sundr. 21: 317-325,1999.
(6) Shin, H. D., Winkler, C., Stephens, J. C., Bream, J., Young, H., Goedert, J.J., O'Brien, T. R., Vlahov, D., Buchbinder, S., Giorgi, J., Rinauldi, C., Donfield, S., Willoughby, A., O'Brien, S.J., and Smith, M.W. Genetic restriction of HIV- 1 infection and AIDS by promoter alleles of Interleukin 10, 1999. PNAS 97: 14467-14472, 2000.
(7) An, P., Martin, M.P., Nelson, G.W., Carrington, M., Smith, M.W., Gong, K., Vlahov, D., Hilgartner, M.W., Phair, J., O'Brien, T., Buchbinder S., O'Brien, S.J., and Winkler, C.A.: Influence of CCR5 promoter haplotypes on AIDS progression in African-Americans. AIDS Journal 14: 2 117-2 122, 2000.
Cheryl A. Winkler 1976 B.S. State University of New York, Albany, NY
1981 M.S. University of Maryland, College Park, MD
1986 Ph.D. University of Maryland, College Park, MD
Brief Chronology of Employment:
1976-1977 - Research Assistant, Montgomery County Public Schools, Rockville, Maryland
1977-1980 - Teaching Assistant, University of Maryland, College Park, MD
1980-1986 Biologist ("P" authority), Section of Genetics, Laboratory of Viral Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland
1986-1987 Immunogenetics Consultant, Intramural Research Support Program, NCI-Frederick Cancer Research & Development Center, Frederick, MD
1987-1995 - Scientist, NCI-Frederick Cancer Research & Development Center, Frederick, MD 1995-1997 Head, Molecular Genetic Epidemiology Section, NCI-Frederick Cancer Research & Development Center Frederick, MD
1997-Date Senior Scientist/Head, Molecular Genetic Epidemiology Section, NCI-Frederick Cancer Research & Development Center, Frederick, MD