Ronald W. Davis, Ph.D., Caltech, 1970

Professor of Biochemistry and Genetics;
Director, Stanford Genome Technology Center

Email:
Web: http://www.stanford.edu/group/biox/clark/davis.html

We are using Saccharomyces cerevisiae and Human to conduct whole genome analysis projects. The yeast genome sequence has approximately 6,000 genes. We have made a set of haploid and diploid strains (21,000) containing a complete deletion of each gene. In order to facilitate whole genome analysis each deletion is molecularly tagged with a unique 20-mer DNA sequence. This sequence acts as a molecular bar code and makes it easy to identify the presence of each deletion. The mixture of all such tag strains then allows for the analysis of the entire genome with the manipulation of a single culture. During growth under a variety of conditions the loss of a tag indicates the loss of a deletion from the population. The concentration of each tag is determined by PCR amplification of the tags and hybridization to an Affymetrix DNA chip that contains the complement to all of the DNA sequence tags. This approach is being applied to other microorganisms.

We have identified a number of wild isolates of yeast that grow at much higher temperatures than is typical for Saccharomyces cerevisiae and are pathogenic and can kill a mouse. Microarrays have been used to map complex genetic traits such as virulence traits in pathogenic Saccharomyces cerevisiae using hybridization to detect single nucleotide polymorphisms. We have developed a new technology termed Recipical Hemizygosity Scanning that allows the determination of the contribution to the phenotype of all pair wise alleles for the whole genome from 2 independent strains. Using this technology we can map and quantitate all of the alleles in the genome for any complex quantitative trait in a single tube assay. These technologies will allow us to explore allelic contributions in complex mixed culture real environments and to investigate ecology at the genome level.

We are conducting a whole genome analysis (transcriptome and proteome) from blood of Human trauma patients. In this large clinical study we are establishing the standards for clinical genomics. We have developed 2 new technologies, "Molecular Inversion Probes" (MIP) for massive multiplex analysis of SNP and DNA content in Human and, "Mismatch Repair Detection" for discovery of rare Human polymorphisms. Both technologies are being applied to numerous clinical investigations.

Select Publications (2005 - present)

Hyman R.W., Fukushima M., Diamond L., Kumm J., Giudice L.C., Davis R.W. (2005). Microbes on the human vaginal epithelium. PNAS 102(22):7952-57.

Apidianakis, Y., Mindrinos, M.N., Xiao, W., Lau, G.W., Baldini, R.L., Davis, R.W., Rahme, L.G. (2005). Profiling early infection responses: Pseudomonas aeruginosa eludes host defenses by suppressing antimicrobial peptide gene expression. Proc Natl Acad Sci U S A 102, 2573-8.

Cobb, J.P., Mindrinos, M.N., Miller-Graziano, C., Calvano, S.E., Baker, H.V., Xiao, W., Laudanski, K., Brownstein, B.H., Elson, C.M., Hayden, D.L., Herndon, D.N., Lowry, S.F., Maier, R.V., Schoenfeld, D.A., Moldawer, L.L., Davis, R.W., Tompkins, R.G., Baker, H.V., Bankey, P., Billiar, T., Brownstein, B.H., Calvano, S.E., Camp, D., Chaudry, I., Cobb, J.P., Davis, R.W., Elson, C.M., Freeman, B., Gamelli, R., Gibran, N., Harbrecht, B., Hayden, D.L., Heagy, W., Heimbach, D., Herndon, D.N., Horton, J., Hunt, J., Laudanski, K., Lederer, J., Lowry, S.F., Maier, R.V., Mannick, J., McKinley, B., Miller-Graziano, C., Mindrinos, M.N., Minei, J., Moldawer, L.L., Moore, E., Moore, F., Munford, R., Nathens, A., O'Keefe, G., Purdue, G., Rahme, L., Remick, D., Sailors, M., Schoenfeld, D.A., Shapiro, M., Silver, G., Smith, R., Stephanopoulos, G., Stormo, G., Tompkins, R.G., Toner, M., Warren, S., West, M., Wolfe, S., Xiao, W, Young, V. (2005). Application of genome-wide expression analysis to human health and disease.  Proc Natl Acad Sci U S A 102, 4801-6.

Padfield KE, Astrakas LG, Zhang Q, Gopalan S, Dai G, Mindrinos MN, Tompkins RG, Rahme LG, Tzika AA. (2005). Burn injury causes mitochondrial dysfunction in skeletal muscle.  Proc Natl Acad Sci U S A. 102(15):5368-73.

Deutschbauer, A.M., Jaramillo, D.F., Proctor, M., Kumm, J., Hillenmeyer, M.E., Davis, R.W., Nislow, C., Giaever, G. (2005). Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast. Genetics 169, 1915-25.

Flaherty, P., Giaever, G., Kumm, J., Jordan, M.I., Arkin, A.P. (2005). A latent variable model for chemogenomic profiling. Bioinformatics 21, 3286-93.

Gharizadeh, B., Oggionni, M., Zheng, B., Akom, E., Pourmand, N., Ahmadian, A., Wallin, K.L., Nyren, P. (2005). Type-specific multiple sequencing primers: a novel strategy for reliable and rapid genotyping of human papillomaviruses by pyrosequencing technology.J Mol Diagn 7, 198-205.

Gu, Z., David, L., Petrov, D., Jones, T., Davis, R.W., Steinmetz, L.M. (2005). Elevated evolutionary rates in the laboratory strain of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 102, 1092-7.

Hardenbol, P., Yu, F., Belmont, J., Mackenzie, J., Bruckner, C., Brundage, T., Boudreau, A., Chow, S., Eberle, J., Erbilgin, A., FFhymanalkowski, M., Fitzgerald, R., Ghose, S., Iartchouk, O., Jain, M., Karlin-Neumann, G., Lu, X., Miao, X., Moore, B., Moorhead, M., Namsaraev, E., Pasternak, S., Prakash, E., Tran, K., Wang, Z., Jones, H.B., Davis, R.W., Willis, T.D., Gibbs, R.A. (2005). Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay. Genome Res 15, 269-75.

Hassibi, A., Contag, C., Vlad, M.O., Hafezi, M., Lee, T.H., Davis, R.W., Pourmand, N. (2005). Bioluminescence regenerative cycle (BRC) system: Theoretical considerations for nucleic acid quantification assays. Biophys Chem 116, 175-85.

Ingram, K.K., Oefner, P, Gordon, D.M. (2005). Task-specific expression of the foraging gene in harvester ants. Mol Ecol 14, 813-8.

Karhanek, M., Kemp, J.T., Pourmand, N., Davis, R.W., Webb, C.D. (2005). Single DNA molecule detection using nanopipettes and nanoparticles.Nano Lett 5, 403-7.

Loftus, B.J., Fung, E., Roncaglia, P., Rowley, D., Amedeo, P., Bruno, D., Vamathevan, J., Miranda, M., Anderson, I.J., Fraser, J.A., Allen, J.E., Bosdet, I.E., Brent, M.R., Chiu, R., Doering, T.L., Donlin, M.J., D'Souza, C.A., Fox, D.S., Grinberg, V., Fu, J., Fukushima, M., Haas, B.J., Huang, J.C., Janbon, G., Jones, S.J., Koo, H.L., Krzywinski, M.I., Kwon-Chung, J.K., Lengeler, K.B., Maiti, R., Marra, M.A., Marra, R.E., Mathewson, C.A., Mitchell, T.G., Pertea, M., Riggs, F.R., Salzberg, S.L., Schein, J.E., Shvartsbeyn, A., Shin, H., Shumway, M., Specht, C.A., Suh, B.B., Tenney, A., Utterback, T.R., Wickes, B.L., Wortman, J.R., Wye, N.H., Kronstad, J.W., Lodge, J.K., Heitman, J., Davis, R.W., Fraser, C.M., Hyman, R.W. (2005). The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans.Science 307, 1321-4.

Qian, W.J., Jacobs, J.M., Camp, D.G., 2nd, Monroe, M.E., Moore, R.J., Gritsenko, M.A., Calvano, S.E., Lowry, S.F., Xiao, W., Moldawer, L.L., Davis, R.W., Tompkins, R.G., Smith, R.D. (2005). Comparative proteome analyses of human plasma following in vivo lipopolysaccharide administration using multidimensional separations coupled with tandem mass spectrometry. Proteomics 5, 572-84.

Qian, W.J., Monroe, M.E., Liu, T., Jacobs, J.M., Anderson, G.A., Shen, Y., Moore, R.J., Anderson, D.J., Zhang, R., Calvano, S.E., Lowry, S.F., Xiao, W., Moldawer, L.L., Davis, R.W., Tompkins, R.G., Camp, D.G., 2nd, Smith, R.D. (2005). Quantitative Proteome Analysis of Human Plasma following in Vivo Lipopolysaccharide Administration Using 16O/18O Labeling and the Accurate Mass and Time Tag Approach. Mol Cell Proteomics 4, 700-709.

Robinson, D.B., Persson, H.H., Zeng, H., Li, G., Pourmand, N., Sun, S., Wang, S.X. (2005). DNA-functionalized MFe2O4 (M = Fe, Co, or Mn) nanoparticles and their hybridization to DNA-functionalized surfaces.  Langmuir 21, 3096-103.

Sivakumaran, T.A., Shen, P., Wall, D.P., Do, B.H., Kucheria, K., Oefner, P.J. (2005). Conservation of the RB1 gene in human and primates. Hum Mutat Apr 25(4):396-409.

Thompson, D., Antoniou, A.C., Jenkins, M., Marsh, A., Chen, X., Wayne, T., Tesoriero, A., Milne, R., Spurdle, A., Thorstenson, Y., Southey, M., Giles, G.G., Khanna, K.K., Sambrook, J., Oefner, P., Goldgar, D., Hopper, J.L., Easton, D., Chenevix-Trench, G. (2005). Two ATM variants and breast cancer risk. Hum Mutat 25, 594-5.

Wall, D.P., Hirsh, A.E., Fraser, H.B., Kumm, J., Giaever, G., Eisen, M.B., Feldman, M.W. (2005). Functional genomic analysis of the rates of protein evolution. Proc Natl Acad Sci U S A 102, 5483-8.

Lee, W., St.Onge R.P., Proctor, M., Flaherty, P., Arkin A.P. , Davis, R.W., Nislow, C., Giaever, G. (2005). Genome-wide requirements for resistance to functionally distinct DNA damaging agents. PLoS Genet 1, e24.

Astrakas, L.G., Goljer, I., Yasuhara, S., Padfield, K.E., Zhang, Q., Gopalan, S., Mindrinos, M.N., Dai, G., Yu, Y.M., Martyn, J.A., Tompkins, R.G., Rahme, L.G. & Tzika, A.A. (2005). Proton NMR spectroscopy shows lipids accumulate in skeletal muscle in response to burn trauma-induced apoptosis. Faseb J 19, 1431-40.

Clayton, D.G., Walker, N.M., Smyth, D.J., Pask, R., Cooper, J.D., Maier, L.M., Smink, L.J., Lam, A.C., Ovington, N.R., Stevens, H.E., Nutland, S., Howson, J.M., Faham, M., Moorhead, M., Jones, H.B., Falkowski, M., Hardenbol, P., Willis, T.D. & Todd, J.A. (2005). Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat Genet 37, 1243-6.

Gharizadeh, B., Akhras, M., Unemo, M., Wretlind, B., Nyren, P. & Pourmand, N. (2005). Detection of gyrA mutations associated with ciprofloxacin resistance in Neisseria gonorrhoeae by rapid and reliable pre-programmed short DNA sequencing. Int J Antimicrob Agents 26, 486-90.

Kivisild, T., Shen, P., Wall, D.P., Do, B., Sung, R., Davis, K.K., Passarino, G., Underhill, P.A., Scharfe, C., Torroni, A., Scozzari, R., Modiano, D., Coppa, A., de Knjiff, P., Feldman, M.W., Cavalli-Sforza, L.L. & Oefner, P.J. (2005). The role of selection in the evolution of human mitochondrial genomes. Genetics.

Kroiss, R., Winkler, V., Bikas, D., Fleischmann, E., Mainau, C., Frommlet, F., Muhr, D., Fuerhauser, C., Tea, M., Bittner, B., Kubista, E., Oefner, P.J., Bauer, P. & Wagner, T.M. (2005). Younger birth cohort correlates with higher breast and ovarian cancer risk in European BRCA1 mutation carriers. Hum Mutat 26, 583-9.

Moorhead, M., Hardenbol, P., Siddiqui, F., Falkowski, M., Bruckner, C., Ireland, J., Jones, H.B., Jain, M., Willis, T.D. & Faham, M. (2005). Optimal genotype determination in highly multiplexed SNP data.Eur J Hum Genet.

Schmitt, S., Prokisch, H., Schlunck, T., Camp, D.G., 2nd, Ahting, U., Waizenegger, T., Scharfe, C., Meitinger, T., Imhof, A., Neupert, W., Oefner, P.J. & Rapaport, D. (2005). Proteome analysis of mitochondrial outer membrane from Neurospora crassa. Proteomics.

van der Zwaag, B., Burbach, J.P., Scharfe, C., Oefner, P.J., Brunner, H.G., Padberg, G.W. & van Bokhoven, H. (2005). Identifying new candidate genes for hereditary facial paresis on chromosome 3q21-q22 by RNA in situ hybridization in mouse. Genomics 86, 55-67.

Vlad, M.O., Szedlacsek, S.E., Pourmand, N., Cavalli-Sforza, L.L., Oefner, P. & Ross, J. (2005). Fisher's theorems for multivariable, time- and space-dependent systems, with applications in population genetics and chemical kinetics. Proc Natl Acad Sci U S A 102, 9848-53.

Yu, F., Sabeti, P.C., Hardenbol, P., Fu, Q., Fry, B., Lu, X., Ghose, S., Vega, R., Perez, A., Pasternak, S., Leal, S.M., Willis, T.D., Nelson, D.L., Belmont, J. & Gibbs, R.A. (2005). Positive Selection of a Pre-Expansion CAG Repeat of the Human SCA2 Gene. PLoS Genet 1, e41.

Last Updated: 2/23/06