MBI 656 | MBI 660, 660A, 668B (labs)
With similar number of genes as in simpler organisms, mammals demonstrate an amazing degree of phenotypic diversity. Mammalian gene expression is under tight regulation temporally and spatially, which contributes to the formation of different cell types, tissues, and organs. Gene regulation involves a complex network of players, including multiple DNA, RNA sequence elements and RNA and protein factors. These regulators interact with each other and carry out combinatorial regulatory functions. Our lab uses both computational and experimental approaches to study the biology of gene regulation from a systems point of view. Our current focus pertains to the regulation of gene expression at the RNA level via the process of pre-mRNA splicing and other post-transcriptional (or co-transcriptional) mechanisms. Splicing is a critical step enabling diversity in gene expression programs. More than 90% of all human genes undergo alternative splicing which allows multiple gene products with potentially different functions to be produced from a single gene locus. We are currently investigating splicing regulatory mechanisms using comparative genomics, high-throughput technologies, such as deep sequencing and microarrays, and systems level computational analysis, such as system identification and modeling approaches. A long-term goal of our research is to better understand the involvement of splicing in gene expression programs of different disease models.
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2. Bahn, J.H., Lee, J.H., Li, G., Greer, C., Peng, G., and Xiao, X., “Accurate identification of A-to-I RNA editing in human by transcriptome sequencing”, Genome Research, 1-9 (2011) .
3. Puppione D.L., Ryan C.M., Bassilian S., Souda P., Xiao X., Ryder O.A., and Whitelegge J.P., “Detection of two distinct forms of apoC-I in great apes”, Comparative Biochemistry and Physiology, Part D, 5 : 73-79 (2010) .
4. Xiao X, Wang Z, Jang M, Nutiu R, Wang ET, Burge CB, “Splice site strength-dependent activity and genetic buffering by poly-G runs”, Nature Structural & Molecular Biology, in press : (2009) .
5. Kalsotra, A., X. Xiao, A. J. Ward, J.C, Castle, J. M. Johnson, C.B. Burge and T.A. Cooper, “A post natal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart”, PNAS, 105 (51): 20333-20338 (2008) .
6. Xiao, X., Z. Wang, M. Jang and C.B. Burge, “Coevolutionary networks of splicing cisregulatory elements”, PNAS, 104 (47): 18583-18588 (2007) .
7. Wang, Z., X. Xiao, E. Van Nostrand and C.B. Burge, “General and specific functions of exonic splicing silencers in splicing control”, Molecular Cel, 23 (1): 61-70 (2006) .
8. Xiao, X., R. Mukkamala, R.J. Cohen, “A weighted-principal component regression method for the identification of physiologic systems”, IDDD Transactions on Biomedical Engineering, 53 (8): 1521-1530 (2006) .
9. Grenon, S.M., X. Xiao, S. Hurwitz, N. Sheynberg, C. Kim, E.W. Seely, R.J. Cohen and G.H. Williams, “Why is orthostatic tolerance lower in women than in men? Renal and cardiovascular responses to simulated microgravity and the role of midodrine”, Journal of Investigative Medicine, 54 (4): 180-190 (2006) .
10. Xiao, X., T.J. Mullen and R. Mukkamala, “System identification: a multi-signal approach for probing cardiovascular neural regulation”, Physiological Measurement, 26 : R41-R71 (2005) .