Department of Biochemistry
School of Medicine & Biomedical Sciences
Faculty
Genomic Approaches to Elucidating Developmental Regulatory Networks
My laboratory investigates the genetic regulatory circuitry responsible for assigning cell fates during development, using the Drosophila embryonic mesoderm as our primary model system. Our work combines genomics and bioinformatics with the traditional molecular and genetic techniques of Drosophila research to investigate two key components of developmental regulatory networks, intercellular signaling and transcriptional regulation. This powerful combination of in silico and in vivo approaches enables us to not only make predictions but also to validate them within specific biological contexts. Our approaches have broad applicability to the study of genomes other than that of Drosophila, including the human genome. Current research in the laboratory falls into two main areas: (a) discovery and characterization of transcriptional cis-regulatory modules (CRMs), and (b) mechanisms of specificity for receptor tyrosine kinase (RTK) signaling. The combined results of our studies will provide insight into gene regulation, genome structure, intercellular signaling, and the regulatory networks that govern embryonic development.
Selected Recent Publications
Leatherbarrow, J.R., and Halfon, M.S. (2009) Identification of receiptor tyrosine kinase signaling target genes reveals receptor-specific activities and pathway branchpoints during Drosophila development. Genetics, 181: 1335-1345. doi:10.1534/genetics.108.098475
Zhu, Q. and Halfon, M.S. (2009). Complex organizational structure of the genome revealed by genome-wide analysis of single and alternative promoters in Drosophila melanogaster. BMC Genomics, 10:9, doi:10.1186/1471-2164-10-9.Ivan, A., Halfon, M. S. and Sinha, S. (2008). Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs. Genome Biology, 9:R22.
Halfon, M. S., Gallo, S. M. and Bergman, C. M. (2008). REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila. Nucleic Acids Res. 36(Suppl_1):D594-598. doi: 10.1093/nar/gkm876.
Li, L., Zhu, Q., He, X., Sinha, S. and Halfon, M. S. (2007). Large-scale analysis of transcriptional cis-regulatory modules reveals
both common features and distinct subclasses. Genome Biology, 8:R101.
Halfon, M. S. (2006). (Re)modeling the transcriptional enhancer. Nat Genet 38(10): 1102-1103.
Choe, S. E., Boutros, M., Michelson, A. M., Church, G. M. and Halfon, M. S. (2005). Preferred analysis methods for Affymetrix GeneChips revealed by a wholly-defined control dataset. Genome Biology. 6:R16.
Halfon, M. S., Grad, Y., Church, G. and Michelson, A.M. (2002). Computation-based discovery of related transcriptional regulatory modules and motifs using a combinatorial model. Genome Res. 12:1019-1028.