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Associate Professor
Short functional peptide motifs Watch 10 minute lecture. Developing protein-protein interaction theory is important for our understanding of the cell, disease mechanisms, and to facilitate drug design. The theory behind protein-protein interactions is based on first principle theory of molecular interactions and the identification of a rapidly growing number of short peptide motifs (less than 15 amino acids) that can bind to, or be acted upon by protein domains. Other than those interactions mediated through short motifs we have virtually no ability to predict protein-protein interactions. My lab is continuing annotation of Minimotif Miner, the first bioinformatics tool that is a comprehensive database of short functional motifs currently containing ~5000 unique motifs (Balla et al, 2006). Minimotif Miner can be used by any scientist to generate new hypotheses about the function of any protein and postulate mechanisms by which mutations cause any human disease (Publications). Current projects are aimed at completing this database, enhancing the specificity of motif definitions and using Minimotif miner to identify new drug targets in HIV (Kadaveru et al, 2008).
Axonal Outgrowth Another central focus of my laboratory is axonal outgrowth. Understanding how neurons initiate axon outgrowth is important, not just for our basic understanding of neuronal connectivity, but also for treating neurodegenerative diseases, spinal cord injury, and head trauma. Axonal outgrowth requires the coordination of many cellular processes. As the axon navigates the nervous system to find targets, it must make complicated decisions that require a higher level of interpretation. Very little is known how the axon is capable of interpreting the many inputs it receives. to address this question, we are continuing to study how a multidomain protein called Kalirin is involved in coordination of axonal signal processing (May et al., 2001; Penzes et al., 2003; Schiller et al., 2005, Schiller et al., 2006, Chakrabarti et al., 2006, Schiller, 2007, Schiller et al., 2008).
We are now using circle plots to compare different experiments to enhance the specificity of motif prediction in our webtool, Minimotif Miner. Above is an example exploring the specficity of a Grb2 SH2 binding motif.
Selected Publications and News:
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Kaiser J (2006) News report about Minimotif miner website. Science 311:925 PDF
Balla S, Thapar V, Verma S, Luong T, Faghri T, Huang C-H, Rajasekaran S, del Campo JJ, Shinn JH, Mohler WA, Maciejewski MW, Gryk MR, Piccirillo B, Schiller SR, and Schiller MR (2006) Minimotif Miner, a tool for investigating protein function. Nature Methods 3:175-177 PDF PMID: 16489333
- Machida K, Thompson CM, Dierck K, Jablonowski , K Karkkainen S, Liu B, Zhang H, Nash PD, Newman DK, Nollau P, Pawson T, Renkema, GH, Saksela K, Schiller MR, Shin DG, and Mayer BJ (2007) "High-Throughput Phosphotyrosine Profiling Using SH2 Domains" Mol. Cell 26:899-915. PDF PMID: 17588523
- Schiller MR (2006) Coupling Receptor Tyrosine Kinases to Rho GTPases - GEFs what's the link. Cell. Signaling 18:1834-1843. PDF PMID: 16725310
- Penzes P, Beeser A, Chernoff J, Schiller MR, Eipper BA, Mains RE, Huganir RL. (2003) Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron 37: 263-74. PDF PMID: 12546821
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Schiller MR (2007) "Minimotif Miner, a computational tool to investigate protein
function, disease, and genetic diversity" Current Protocols in Protein Science, Eds. Coligan JE, Dunn BM, Speicher DW, Winkler H., Unit 2.12.1 - 2.12.14 John Wiley & Sons, Inc. PDF -
Schiller MR, Chakrabarti K, King GF, Schiller NI, Eipper BA, and Maciejewski MW (2006) Regulation of RhoGEF activity by intramolecular and intermolecular SH3 interactions J. Biol. Chem. 281:17774-17786 PDF PMID: 16644733
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Chakrabarti K, Lin R, Schiller NI, Wang Y, Fan Y-X, Koubi D, Rudkin BB, Johnson GR, Schiller MR. (2005) A critical role for Kalirin in NGF signaling through TrkA. Mol. Cell. Biol. 25:5106-5118. PDF PMID: 15923627