John Stamatoyannopoulos

Associate Professor of Genome Sciences

phone: (206) 267-1098 | fax: (206) 267-1094
Foege S-310A, Box 355065
jstam [ a t ] u.washington.edu

Research:

Reading the Human Genome. The ability to read the human genome sequence is critical for realizing its potential to inform and transform biology, medicine, and human health.  Protein coding gene sequences occupy only about 1.5% of the human genome.  Hidden in the remaining 98.5% are the instructions that encode the timing, magnitude, and cellular spectrum of gene expression.   It is widely believed that a significant fraction (if not the majority) of disease-causing alleles in humans are localized within regulatory DNA.  Major goals of my laboratory are to:

  • Comprehensively map regulatory DNA across cell types and during development and differentiation in humans and major model organisms

  • Develop a regulatory genetic code analogous to the classical genetic code for proteins that will enable generalized interpretation of the significance of genetic variation within regulatory DNA

  • Pioneer novel technologies for rapid identification and quantification of the sequence-specific DNA binding proteins that actuate regulatory DNA

  • Develop new computational approaches for modeling regulatory genomic systems

Comprehensive atlases of regulatory DNA. We aim to create comprehensive catalogs of regulatory DNA that encompass major cell and tissue types from diverse organisms.  Ongoing efforts include regulatory DNA atlases for human, mouse, selected primates, zebrafish, Drosophila, and Arabidopsis.  Large scale efforts with rapid public data release are funded through the following NIH and NSF programs:

  • The ENCODE Project (NHGRI)

  • Roadmap Epigenomics Project and Reference Epigenome Mapping Centers (NIEHS / NIH Common Fund)

  • The Mouse ENCODE Project (NHGRI)

  • The Arabidopsis 2010 Project (NSF)

Technology development. Together with diverse collaborators in bioengineering, biophysics, mechanical engineering, crystallography, and analytical chemistry we are developing the next generation of tools and technologies for analysis of living genomes.  Examples include technologies for:

  • Massively parallel, genome-scale profiling of protein:DNA interactions in vivo

  • Direct sequencing of chromatin fibers using silicon nanodevices and quantum dot nanocrystals

  • Atomic resolution modeling of protein:DNA interactions

  • Simultaneous, highly sensitive quantification of all human DNA binding proteins

  • Cost-effective analysis of chromatin and DNA methylation on an epidemiological scale

Biological systems. We are applying our technologies to study diverse systems relevant to major aspects of human biology, physiology, and disease pathogenesis.   These include:

  • Chromatin programming during development and differentiation

  • Inherited variation in human gene regulation

  • Regulatory genomics of cancer and inflammation

Selected Publications:

Hesselberth JR, Chen X, Zhang Z, Sabo PJ, Sandstrom R, Reynolds AP, Thurman RE, Neph SJ, Kuehn MS, Noble WS, Fields S, Stamatoyannopoulos JA. (2009) Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nature Methods, 6:283-9.

Hansen RS, Thomas S, Sandstrom R, Canfield T, Thurman RE, Weaver M, Dorschner MO, Gartler SM, Stamatoyannopoulos JA. (2009). Widespread plasticity in human DNA replication time. Proc. Nat’l Acad. Sci. USA, 107:139-44

Stamatoyannopoulos JA, Adzhubey I, Thurman RE, Kryukov GV, Mirkin SM, Sunyaev S. (2009). Human mutation rate associated with DNA replication timing. Nature Genetics, 41:393-5.

The ENCODE Project Consortium. (2007). Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:782-3

Thurman RE, Day N, Noble WS, Stamatoyannopoulos JA. (2007) Identification of higher-order functional domains in the human genome. Genome Research 17:917-27.

Asthana S, Noble WS, Kryukov G, Grant CE, Sunyaev S, Stamatoyannopoulos, JA. (2007) Widely distributed non-coding selection in the human genome.,Proc Nat'l Acad Sci USA 104:12410-5.

Sabo PJ, Kuehn MS, Thurman R, Johnson BE, Johnson EM, Cao H, Yu M, Rosenzweig E, Goldy J, Haydock A, Weaver M, Shafer A, Lee K, Neri F, Humbert R, Singer MA, Richmond TA, Dorschner MO, McArthur M, Hawrylycz M, Green RD, Navas PA, Noble WS, Stamatoyannopoulos JA. (2006). Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nature Methods 3:511-8.

Dorschner MO, Hawrylycz M, Humbert R, Wallace JC, Shafer A, Mack J, Hall R, Goldy J, Kawamoto J, Sabo PJ, McArthur M, Stamatoyannopoulos JA. (2004). High-throughput localization of functional elements by quantitative chromatin profiling. Nature Methods 1:219-225 .

Sabo PJ, Hawrylycz M, Wallace JC, Humbert R, Shafer A, Kawamoto J, Mack J, Hall R, Kohli A, Li Q, McArthur M, Stamatoyannopoulos JA. (2004). Discovery of functional non-coding elements by digital analysis of chromatin structure. Proc. Nat’l. Acad. Sci. USA 101:16837-16842.