Biography:

Dr. Smith is one of the world’s experts on using admixture to discover genes that underlie disparities in disease between racial and ethnic groups. Dr. Smith earned his Ph.D. from the Johns Hopkins University in the area of population genetics in 1989, trained in molecular evolution at the University of California, San Diego and then joined the Salk Institute for Biological Studies where he became the Assistant Director of the Human Genome Center focused on human chromosome 11. While at the Salk Institute, he developed genomic sequence sampling (now a division of Genbank). Dr. Smith has worked for the operational and technical support contractor (SAIC-Frederick) at the National Cancer Institute at Frederick since 1994 on a novel gene identification technique (Mapping by Admixture Linkage Disequilibrium), HIV-1/AIDS host genetics, the role of IL10 gene in disease, using genes as biomarkers in epidemiological studies and more generally on human disease genetics.

Research:

The completion of International HapMap project, and a fuller understanding of the tremendous diversity of the human genome generated opportunities that were not even dreamed of at the initiation of the human genome project. The opportunity to examine humans from the vista of an annotated genome sequence and a good characterization of its diversity is being pursued on several fronts in my laboratory. One, an examination of genes thought to be involved in HIV-1/AIDS, HCV, HBV and other infectious diseases for effects on disease progression and infection. Two, development and application of a novel method of gene identification called Mapping by Admixture Linkage Disequilibrium (MALD) through analysis of select regions, and the entire genome for admixture linkage disequilibrium (ALD) and developing new MALD marker set have been pursued as part of the MALD strategy. Three, examination of more traditional linkage disequilibrium (LD) and genetic association, primarily around the IL10 locus, for discovery of functional genetic variants. Four, development and application of methodologies for determination if a biological mixture is present has been applied to the sharing-status of syringes to further our understanding of a major route of infectious disease transmission. These multidisciplinary efforts represent approaches underway in the laboratory aimed at understanding human disease using genetics and genomics. (click to read more research details)

Featured Publications:

Smith, M.W., Holmsen, A.L., Peterson, M., Wei, Y.H., and Evans, G.A. Genomic sequence sample analysis: a rapid strategy for sequence-based physical mapping of complex genomes. Nat Genet 7: 40–47, 1994.

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. and 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 273:1856-62, 1996.

Smith, M.W., Dean, M., Carrington, M., Winkler, C., Huttley, G.A., Lomb, D.A., Goedert, J.J., O’Brien, T.R., Muñoz, A., Jacobson, L.P., Buchbinder, S., Vittinghoff, E., Vlahov, D., Hoots, K., Hilgartner, M., HGDS, Multicenter AIDS Cohort, 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 277:959-65, 1997.

Martin, M.P., Dean, M., Smith, M.W., Winkler, C., Gerrard, B., Michael, N.L., Margolick, J., Buchbinder, S., Goedert, J.J., O’Brien, T.R., Hilgartner, M.W., Hoots, K., Vlahov, D., O’Brien, S.J., and Carrington, M. Genetic acceleration of AIDS progression by a promoter variant of CCR5. Science 282: 1907–1911, 1998.

Winkler, C., Modi, W., Smith, M.W., Nelson, G.W., Wu, X., Carrington, M., Dean, M., Honjo, T., Tashiro, K., Yabe, D., Vittinghoff, E., Buchbinder, S., Goedert, J.J., O’Brien, T.R., Jacobson, L.P., 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 SDF1 chemokine gene mutation. Science 279: 389–393, 1998

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., Rinaldo, C., Donfield, S., Willoughby, A., O’Brien, S.J., and Smith, M.W. Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL 10. Proc Natl Acad Sci USA 97:14467-72, 2000.

Smith, M.W., Patterson, N., Lautenberger, J.A., Truelove, A.L., McDonald, G.J., Waliszewska, A., Kessing, B.D., Malasky, M.J., Scafe, C., Le, E., De Jager, P.L., Mignault, A.A., Yi, Z., de The, G., Essex, M., Sankale, J.L., Moore, J.H., Poku, K., Phair, J.P., Goedert, J.J., Vlahov, D., Williams, S.M., Tishkoff, S.A., Winkler, C.A., De La Vega, F.M., Woodage, T., Sninsky, J.J., Hafler, D.A., Atshuler, D., Gilbert, D.A., O’Brien, S.J., and Reich, D. A high density admixture map for disease gene discovery in African Americans. Am J Hum Genet 74:1001-13, 2004.

Patterson, N., Hattangadi, N., Lane, B., Lohmueller, K., Hafler, D.A., Oksenberg, J.R., Hauser, S.L., Smith, M.W., O’Brien, S.J., Atshuler, A., Daly, M.N., and Reich, D. Methods for high-density admixture mapping of disease genes. Am J Hum Genet 74:979–1000, 2004.

Silverberg, M.J., Smith, M.W., Chmiel, J.S., Detels, R., Margolick, J.B., Rinaldo, C.R., O’Brien, S.J., Munoz, A. Fraction of AIDS cases prevented by the interactions of identified restriction gene variants. Am J Epidemiol 159: 232–241, 2004.

Smith, M.W., and O’Brien, S.J. Mapping by admixture linkage disequilibrium: advances, limitations and guidelines. Nat Rev Genet 6:623-62, 2005.

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