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Xin Sun 56 Gardener Street Apt 8, Allston, MA 02134 Phone: 781-296-7882 (Cell) Email: [email protected]

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Xin Sun 56 Gardener Street Apt 8, Allston, MA 02134 Phone: 781-296-7882 (Cell) Email: Xinsun@Bu.Edu Xin Sun 56 Gardener Street Apt 8, Allston, MA 02134 Phone: 781-296-7882 (Cell) Email: [email protected] EDUCATION Brandeis University, Waltham, MA, 2005 – 2011 Ph.D. in Biochemistry Advisor: Lizbeth Hedstrom University of California, Berkeley, Berkeley, CA, 2001 - 2005 B.A. in Molecular and Cell Biology, Division of Biochemistry and Molecular Biology RESEARCH SUMMARY Boston University, Boston, MA, 2011 – present Moenomycin A (MmA) is the prototypical phosphoglycolipid antibiotic produced by Streptomyces spp. and is the only known active site inhibitor of the peptidoglycan glycosyltransferases (PGT) , the bacterial cell wall sugar polymerases. A mechanistically intriguing methylation of an sp3-hybridized carbon occurs during MmA biosynthesis; this reaction is catalyzed by MoeK5, a cobalamin radical-SAM methyltransferase, but the mechanism is not understood. My work has focused on the expression, purification, and reconstitution of MoeK5 with its two complex metal cofactors, methylcobalamin and an iron-sulfur cluster. Furthermore, biochemical analysis of MmA production demonstrates that methylation occurs early in the MmA biosynthetic pathway. Using MmA biosynthetic enzymes, I have chemo-enzymatically synthesized the likely MoeK5 sugar-lipid substrate. I am currently poised to carry out a detailed mechanistic study of this elusive class of enzymes. Brandeis University, Waltham, MA, 2005 – 2011 Cryptosporidium parvum is a eukaryotic, disease causing human pathogen for which there are no vaccines or drugs available. Genomic analysis suggests the parasite is almost entirely dependent on salvage pathways for the synthesis of metabolites. In my research, I enzymatically characterized one of the parasite’s pyrimidine salvage enzymes, thymidine kinase, and assessed its role both as a potential drug target and in the activation of prodrugs. We showed that C. parvum thymidine kinase activates trifluorothymidine, a nucleoside analog prodrug, which causes an effective reduction of parasite load in both in vitro and in vivo models of infection. Mycophenolic acid (MPA) is a small molecule secondary metabolite produced by several Penicillium strains. MPA is a billion-dollar immunosuppressant drug and acts by inhibiting the enzyme IMP dehydrogenase (IMPDH). My research uncovered a novel mechanism of drug resistance by showing that P. brevicompactum contains an IMPDH with a different kinetic mechanism than all other IMPDHs studied to date. This unique kinetic mechanism minimizes the drug-sensitive enzyme form, thus rendering the enzyme insensitive to inhibition. TECHNICAL SKILLS Biochemistry techniques: recombinant protein expression, chromatography (affinity, ion exchange, reverse-phase, FPLC, HPLC), enzyme assays, steady-state kinetics, pre-steady-state kinetics, inhibitor analysis. Molecular biology techniques: molecular cloning, site-directed mutagenesis Synthesis: nucleotide synthesis, chemo-enzymatic synthesis Spectroscopy and instrumentation: UV-Vis, Fluorescence, plate reader, QTOF mass spectrometry, anaerobic techniques TEACHING EXPERIENCE Teaching Assistant, Brandeis University, Waltham, MA, 2006 – 2007 Courses: Advanced Biochemistry: Enzyme Mechanisms Professor: Lizbeth Hedstrom Introductory Biochemistry Professor: Gregory Petsko PUBLICATIONS Research papers: Sun, X. E., Sharling, L., Muthalagi, M., Mudeppa, D. G., Pankiewicz, K. W., Felczak, K., Rathod, P. K., Mead, J., Striepen, B., and Hedstrom, L. (2010) Prodrug Activation by Cryptosporidium Thymidine Kinase, Journal of Biological Chemistry 285, 15916-15922. Sun, X. E., Hansen, B. G., and Hedstrom, L. (2011) Kinetically Controlled Drug Resistance, Journal of Biological Chemistry 286, 40595-40600. Hansen, B. G., Sun, X. E., Genee, H. J., Kaas, C. S., Nielsen, J. B., Mortensen, U. H., Frisvad, J. C., and Hedstrom, L. (2012) Adaptive evolution of drug targets in producer and non-producer organisms, Biochem J 441, 219-226. Reviews: Gorla, S. K., Johnson, C., Khan, J., Sun, X., Sharling, L., Striepen, B. and Hedstrom, L. (2011) Targeting Prokaryotic Enzymes in the Eukaryotic Pathogen Cryptosporidium, in Apicomplexan Parasites: Molecular Approaches toward Targeted Drug Development (ed K. Becker), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527633883.ch14 PRESENTATIONS “Characterization of thymidine kinase from Cryptosporidium parvum: assessment of a potential drug target and its role in parasitic growth” (Poster) 19th Annual Molecular Parasitology Meeting, Woods Hole, MA, September 2008. “Trifluorothymidine may be a promising drug for Cryptosporidiosis: understanding the mechanism of its anti-parasitic activity” (Poster) 20th Annual Molecular Parasitology Meeting, Woods Hole, MA, September 2009. “Kinetically Controlled Drug Resistance: How Penicillium brevicompactum Survives” (Poster) Shifting the Paradigms of Drug Resistance Meeting, Worcester, MA, October 2010. “Kinetically Controlled Drug Resistance: How Penicillium brevicompactum Survives” (Poster) 22nd Enzyme Mechanisms Conference, St. Pete Beach, FL, January 2011. REFERENCES Dr. Lizbeth Hedstrom (Ph.D. advisor) Professor of Biology and Chemistry, Brandeis University 781-736-2333 [email protected] Dr. Deborah Perlstein (Postdoctoral advisor) Assistant Professor of Chemistry, Boston University 617-358-6180 [email protected] Dr. Daniel Oprian Professor of Biochemistry, Brandeis University 781-736-2322 [email protected] .
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