This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Recent technological developments enable two complementary approaches to mapping the signaling and regulatory circuitry inside cells. First, it is possible to directly measure the wires themselves, by screening for protein-protein and protein-DNA interactions using systematic protein (Gavin et al., 2002) and chromatin immunoprecipitation (Ren et al., 2000) experiments. Second, we can measure the molecular and cellular states induced by the wiring. For example, changes in gene expression are measured with DNA microarrays (DeRisi et al., 1997), while changes in protein abundance (Gygi et al., 1999), protein phosphorylation state (Zhou et al., 2001), and metabolite concentrations (Griffin et al., 2001) may be quantitated with mass spectrometry, NMR, and other advanced techniques. In this proposal we combine both of these approaches in a multi-tiered pathway mapping strategy. First, large databases of protein-protein and protein-DNA interactions are used to define a global network or wiring scaffold . Second, this scaffold is filtered against changes in mRNA expression, protein expression, and post-translational modifications (i.e., phosphorylation) recorded in response to different cellular perturbations. Regions of the wiring scaffold whose mRNA or protein states are significantly activated by perturbation are identified and mapped according to a computational search algorithm. The interaction pathways and complexes making up each activated region in the scaffold become prime candidates for further verification and modeling as important signaling and compensatory mechanisms controlling the cell s perturbation response.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BECM (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Hagen, Susan E; Liu, Kun; Jin, Yafei et al. (2018) Synthesis of CID-cleavable protein crosslinking agents containing quaternary amines for structural mass spectrometry. Org Biomol Chem 16:8245-8248
Pai, Dave A; Kaplan, Craig D; Kweon, Hye Kyong et al. (2014) RNAs nonspecifically inhibit RNA polymerase II by preventing binding to the DNA template. RNA 20:644-55
Zhang, Chunchao; Gao, Shan; Molascon, Anthony J et al. (2014) Bioinformatic and proteomic analysis of bulk histones reveals PTM crosstalk and chromatin features. J Proteome Res 13:3330-7
Johnson, Cole; Kweon, Hye Kyong; Sheidy, Daniel et al. (2014) The yeast Sks1p kinase signaling network regulates pseudohyphal growth and glucose response. PLoS Genet 10:e1004183
Zhang, Chunchao; Gao, Shan; Molascon, Anthony J et al. (2014) Quantitative proteomics reveals histone modifications in crosstalk with H3 lysine 27 methylation. Mol Cell Proteomics 13:749-59
Zhang, Yan; Kweon, Hye Kyong; Shively, Christian et al. (2013) Towards systematic discovery of signaling networks in budding yeast filamentous growth stress response using interventional phosphorylation data. PLoS Comput Biol 9:e1003077
Simon, E S; Papoulias, P G; Andrews, P C (2013) Selective collision-induced fragmentation of ortho-hydroxybenzyl-aminated lysyl-containing tryptic peptides. Rapid Commun Mass Spectrom 27:1619-30
Zhang, Chunchao; Molascon, Anthony J; Gao, Shan et al. (2013) Quantitative proteomics reveals that the specific methyltransferases Txr1p and Ezl2p differentially affect the mono-, di- and trimethylation states of histone H3 lysine 27 (H3K27). Mol Cell Proteomics 12:1678-88
Gao, Shan; Xiong, Jie; Zhang, Chunchao et al. (2013) Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation. Genes Dev 27:1662-79
Zhang, Chunchao; Liu, Yifan; Andrews, Philip C (2013) Quantification of histone modifications using ยน?N metabolic labeling. Methods 61:236-43

Showing the most recent 10 out of 56 publications