Xuewen Pan, Ph.D.
Department of Biochemistry and Molecular Biology
Department of Molecular and Human Genetics
- 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
Drug mechanisms of action and resistance
Key to the safety and efficacy of a therapeutic drug is our understanding of its mechanism(s) of actions and mechanisms of possible resistance in vivo. A major interest of the lab is to elucidate such mechanisms of existing and novel drugs using functional genomic tools such as screening genome-wide mutant and gene overexpression libraries for altered drug sensitivity, genome-wide genetic network analyses, and gene expression profiling. Equally important, we are also building novel functional genomic tools to facilitate these studies both in yeast and in human cell culture system.
Sister chromatid cohesion
Physical cohesion between duplicated sister chromatids is essential for faithful chromosome segregation and DNA recombination repair. Sister chromatid cohesion is mediated by a cohesin complex consisting of Smc1, Smc3, Scc1/Rad21, and Scc3. By collaborating with Dr. Jun Qin's group, we found that acetylation of two conserved lysine residues (K112 K113 in yeast and K105 K106 in human) by the acetyltransferase Eco1 is critical for sister chromatid cohesion. Using the budding yeast as a model system, we are currently taking a combination of genetic, biochemical, and cell biological approach to elucidate how Smc3 acetylation leads to the establishment of sister chromatid cohesion. We are also characterizing novel factors identified from a genetic screen that likely regulate Eco1-dependent Smc3 acetylation and sister chromatid cohesion.
Genetic determinants of homologous recombination
Homologous recombination is critical for genomic stability and meiotic reproduction. Many factors are involved in this important process. By screening a genome-wide gene deletion mutant library, we have identified dozens of known as well as novel genes that affect the rate of homologous recombination in yeast. We also identified important features of genome organization that dictate the rate of recombination. We are currently characterizing some of these novel factors for the molecular mechanisms by which they regulate recombination.
- Matecic M, Smith DL, Pan X, Maqani N, Bekiranov S, Boeke JD, Smith JS. A microarray-based genetic screen for yeast chronological aging factors. PLoS Genet. 2010 Apr 22;6(4):e1000921. [PubMed]
- Pan X, Reissman S, Douglas NR, Huang Z, Yuan DS, Wang X, McCaffery JM, Frydman J, Boeke JD. Trivalent arsenic inhibits the functions of chaperonin complex. Genetics. 2010 Oct;186(2):725-34. [PubMed]
- Kim JH, Zhao Y, Pan X, He X, Gilbert HF. The unfolded protein response is necessary but not sufficient to compensate for defects in disulfide isomerization. J Biol Chem. 2009 Apr 17;284(16):10400-8. [PubMed]
- Huang Z, Sucgang RS, Lin YY, Shi X, Boeke JD, Pan X. Plasmid-chromosome shuffling for non-deletion alleles in yeast. Nat Methods. 2008 Feb;5(2):167-9. [PubMed]
- Li F, Dong J, Pan X, Oum JH, Boeke JD, Lee SE. Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates. Mol Cell. 2008 May 9;30(3):325-35. [PubMed]
- Lin YY, Qi Y, Lu JY, Pan X, Yuan DS, Zhao Y, Bader JS, Boeke JD. A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation. Genes Dev. 2008 Aug 1;22(15):2062-74. [PubMed]
- Zhang J, Shi X, Li Y, Kim BJ, Jia J, Huang Z, Yang T, Fu X, Jung SY, Wang Y, Zhang P, Kim ST, Pan X, Qin J. Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast. Mol Cell. 2008 Jul 11;31(1):143-51. [PubMed]
- Pan X, Ye P, Yuan DS, Wang X, Bader JS, Boeke JD. A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell. 2006 Mar 10;124(5):1069-81. [PubMed]
- Arévalo-Rodríguez M, Pan X, Boeke JD, Heitman J. FKBP12 controls aspartate pathway flux in Saccharomyces cerevisiae to prevent toxic intermediate accumulation. Eukaryot Cell. 2004 Oct;3(5):1287-96. [PubMed]
- Pan X, Yuan DS, Xiang D, Wang X, Sookhai-Mahadeo S, Bader JS, Hieter P, Spencer F, Boeke JD. A robust toolkit for functional profiling of the yeast genome. Mol Cell. 2004 Nov 5;16(3):487-96. [PubMed]