Patrick O. Brown, M.D.
Ph.D., 1980, M.D., 1982, Chicago
Professor of Biochemistry
E-mail:
Web: http://cmgm.stanford.edu/pbrown
The genome project has revitalized exploration in biological research. Seeing the complete repertoire of genes in a genome confronts us with the fact that we know the biochemical activities and the biological functions of only a tiny fraction of the genes and proteins that make up a living organism. The discovery of this genetic "terra incognita" has reminded us how much of the living world is beyond the frontier, and challenged us to explore this new world.
The torrent of DNA sequences has not only made a new era of exploration imperative, but also made it possible: Nucleic acid hybridization provides a simple, direct, way to use the DNA sequence of a gene as a specific assay reagent to detect and monitor that gene and its activity. We have therefore developed a convenient tool, a "DNA microarray", that uses nucleic acid hybridization to monitor thousands of genes at once.
A DNA microarray can be used as a new kind of microscope that allows us to observe a genome’s gene expression program. Each cell in our bodies expresses a specific set of genes according to a precisely controlled genetic script that gives that cell its distinctive design and functional capabilities. The gene expression program that unfolds during a developmental or physiological or pathological process can be read as a kind of a script for that process.
We have launched a systematic effort to survey and map out the gene expression script of the yeast genome – how the global gene expression program responds to the diverse challenges yeast encounter in nature. One important kind of information we can get from these studies is a detailed picture of the rules that govern expression of each gene. Because the expression pattern of a gene is closely tied to its biological role, systematic studies of global gene expression provide clues to the functions of thousands of genes. We are also developing new genetic and biochemical approaches, using DNA microarrays to systematically map out the regulatory circuitry and the metabolic machinery that controls that synthesis, processing, trafficking, translation and degradation of each gene’s transcripts. Because we suspect that inherited variation in the gene expression scripts is an important source of the diversity of forms and lifestyles among yeast in nature, we are systematically mapping the genes that control differences in the gene expression script in yeast strains found in different natural environments.
We use DNA microarrays containing up to 30,000 different human genes to survey the gene expression patterns in thousands of samples of human cells and tissues under diverse conditions. These studies are providing detailed molecular pictures of the programmed responses of the human genome to diverse physiological and pathological conditions, and they are yielding clues to the mechanisms by which these processes are deranged in cancer and other disease processes.
Just as DNA microarrays have allowed us to measure the transcripts of thousands of genes at once, we have recently found that we can use microarrays of specific antibodies to measure the abundance of thousands of different proteins in samples from cells, or in biological fluids, like serum or urine. We are now actively exploring the possible application of protein microarrays in monitoring health and detecting and diagnosing disease.
Select Publications (2005 - present)
Ball CA, Awad IA, Demeter J, Gollub J, Hebert JM, Hernandez-Boussard T, Jin H, Matese JC, Nitzberg M, Wymore F, Zachariah ZK, Brown PO, Sherlock G. (2005). The Stanford Microarray Database accommodates additional microarray platforms and data formats. Nucleic Acids Res. 33:D580-2.
Shyamsundar R, Kim YH, Higgins JP, Montgomery K, Jorden M, Sethuraman A, van de Rijn M, Botstein D, Brown PO, Pollack JR. (2005). A DNA microarray survey of gene expression in normal human tissues. Genome Biol.6:R22.
Chang HY, Nuyten DSA, Sneddon JB, Hastie T, Tibshirani R, Sorlie T, Dai H, He Y, van’t Veer L, Bartelink H, van de Rijn M, Brown PO, van de Vijver MJ. (2005). Robustness, Scalability, and Integration of a Wound Response Gene Expression Signature in Predicting Survival of Human Breast Cancer Patients. Proc Natl Acad Sci U S A102(10):3738-43.
Liang Y, Diehn M, Watson N, Bollen AW, Adape KD, Nicholas MK, Lamborn KR, Berger MS, Botstein D, Brown PO, Israel MA. (2005). Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc Natl Acad Sci U S A102(16):5814-9.
Arava Y, Boas E, Brown PO, Herschlag D. (2005). Dissecting Eukaryotic Translation and Its Control by Ribosome Density Mapping. Nucleic Acids Res. 33(8):2421-32.
West R, Nuyten DSA, Montgomery K, Nilson TO, Rubin BP, van de Vijver MJ, Brown PO, van de Rijn M. (2005). Determination of stromal signatures in breast carcinoma. PLoS Biol. 3(6):e187.
Diehn JJ, Diehn M., Marmor MF, Brown PO. (2005). Differential gene expression in anatomical compartments of the human eye. Genome Biol. 6(9):R74.
Chen DS, Soen Y, Stuge TB, Lee PP, Weber JS, Brown PO, Davis MM. (2005). Marked differences in human melanoma antigen-specific Y cell responsiveness after vaccination using a functional microarray. PloS Med. 2(10):e265.
West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, Zhu S, Marinelli RJ, De Luca A, Downs-Kelly E, Goldblum JR, Corless CL, Brown PO, Gilks CB, Nielsen TO, Huntsman D., van de Rjin M. (2006). A landscape effect in ternosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A. 103(3):690-5.
Palmer C, Bik EM, Eisen MB, Eckburg PB, Sana TR, Wolber PK, Relman DA, Brown PO. (2006). Rapid quantitative profiling of complex microbial populations. Nucleic Acids Res. 34(1):e5.
Diehn M, Bhattacharya R, Botstein D, Brown PO. (2006). Genome-Scale Identification of Membrane-Associated Human mRNAs. PloS Genet. 2(1):e11.
Chi JT, Wang Z, Nuyten DS, Rodriquez EH, Schaner ME, Salim A, Wang Y, Kristensen GB, Helland A, Borresen-Dale AL, Giaccia A, Longaker MT, Hastie T, Yang GP, Vijver MJ, Brown PO. (2006). Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers. PloS Med. 3(3):e47.
Last Updated: 2/23/06
