Xuewen Pan, Ph.D.
Assistant Professor
Dept. of Biochemistry & Molecular Biology
Dept. of Molecular & Human Genetics
Education and Awards
- B.S., Huazhong Agricultural University, Wuhan, P. R. China, 1993
- Ph.D., Duke University Medical Center, North Carolina, 2001
- Postdoctoral Training, Johns Hopkins University School of Medicine, Maryland, 2006
Genetic Networking
Emerging evidence suggests that most biological functions are carried out by pathways consisting of multiple components rather than by single gene products alone. These pathways further interconnect to form a robust biological network that defines life. In this post genome era, a daunting task is, in addition to understand the functions of each gene product, to identify the pathway structures and network connectivity among the thousands of gene products encoded by a genome. We address these questions using the baker's yeast Saccharomyces cerevisiae as a model system. We have developed a methodology called dSLAM (heterozygous diploid-based Synthetic Lethality Analysis on Microarrays) for studying various types of genome-wide genetic interactions, including both synthetic lethality and genetic suppression, in a high throughput manner by using the yeast knockout (YKO) mutants. These genetic interactions could be effectively used to assign genes into the same or functionally compensatory pathways. This technology has been used to dissect the genetic network and pathway topologies governing DNA integrity in yeast. Currently, we are vigorously characterizing this network in greater detail with a combination of functional genomics, proteomics, and traditional molecular biology approaches. In addition, we are applying the dSLAM technology to study pathways involved in other biological processes.
Chemical Genomics
Technologies profiling the YKO mutants such as dSLAM could be effectively exploited to investigate the mechanisms of actions of anti-proliferation small molecules and to identify the genetic determinants that dictates individual's susceptibility to therapeutic drugs and environmentally hazardous compounds. Comparing to other methodologies, dSLAM has the added advantage of studying these problems in a network context. We have used this technology to study the effects of several poorly characterized anti-cancer and anti-malaria drugs on yeast and gained interesting insight into both their mechanisms of actions and the genetic networks involving the drug targets. A short-term goal of ours is to identify as many as possible the targets of existing poorly characterized therapeutic compounds and health-threatening environmental contaminants with yeast as a platform. Our long-term goal is to search for novel bioactive chemicals as potential therapeutic compounds or biological probes.
Technology Development
Another active area of our research is to continue developing cutting edge functional genomics tools for studying both genetic networks and chemical genomics.
Selected Publications
1. Pan, X, Yuan DS, Ooi SL, Wang X, Sookhai-Mahadeo, S, Meluh P, Boeke JD (2006). dSLAM analysis of genome-wide genetic interaction in Saccharomyces cerevisiae. Methods, in press.
2. Ooi SL, Pan X, Peyser BD, Ye P, Meluh PB, Yuan DS, Irizarry RA, Bader JS, Spencer FA, Boeke JD (2006). Global synthetic-lethality analysis and yeast functional profiling. Trends Genet. 22: 56-63.
3. Pan X, Ye P, Yuan DS, Wang X, Bader JS, Boeke JD (2006). A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell 124:1069-1081.
4. Ye P, Peyser BD, Pan X, Boeke JD, Spencer FA, Bader JS (2005). Gene function prediction from congruent synthetic lethal interactions in yeast. Mol. Syst. Biol. Epub doi:10.1038/msb4100034.
5. Yuan DS, Pan X, Ooi SL, Peyser BD, Spencer FA, Irizarry RA, Boeke JD (2005). Improved microarray methods for profiling the Yeast Knockout strain collection. Nucleic Acids Res. 33: e103.
6. Pan X, Yuan DS, Xiang D, Wang X, Sookhai-Mahadeo S, Bader JS, Hieter P, Spencer F, Boeke JD (2004). A robust toolkit for functional profiling of the yeast genome. Mol. Cell 16: 487-496.
7. Pan X, Heitman J (2002). Protein kinase A operates a molecular switch that governs yeast pseudohyphal differentiation. Mol. Cell. Biol. 22: 3981-3993.
8. Cutler NS, Pan X, Cardenas ME (2001). The TOR signal transduction cascade controls cellular differentiation in response to nutrients. Mol. Biol. Cell 12: 4103-4113.
9. Pan X, Harashima T, Heitman J (2000). Signal transduction cascades regulating pseudohyphal differentiation of Saccharomyces cerevisiae. Curr. Opin. Microbiol. 3: 567-572.