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Research Interests: Molecular Genetics of Human Parasites

Our laboratory studies the protozoan parasite Leishmania, a relative of trypanosomes which infects more than 10 million people in tropical regions. We especially wish to understand the infectious cycle of the parasite, which normally consists of an intracellular stage within the phagolysosome of the vertebrate macrophage and an extracellular stage within the gut of a sand fly vector. Studies of these parasites have lead to the discovery of an astonishing array of novel molecular mechanisms that are now paradigms in higher eukaryotes, including RNA editing, trans-splicing, GPI anchors, bent DNA, and the Th1-Th2 T-cell subset paradigm.

Most projects in the lab focus on the use of functional genetic complementation and transfection to identify and dissect new Leishmania genes of interest. These approaches take into account the fact that the parasite is diploid and lacks an experimentally manipulable sexual cycle. We have developed several approaches for creating mutants, using powerful genetic selections or FACS manipulation of parasites selectively expressing the green fluorescent protein (GFP). We have characterized and now routinely use the phenomenon of loss-of-heterozygosity (LOH) for the creation of homozygous mutants.

One powerful system for identifying mutations defective in the synthesis of a surface glycoconjugate, lipophosphoglycan (LPG), which is an essential virulence determinant involved in adhesion and survival. Using a simple combination of lectin selections for or against surface LPG expression, we have identified a large panel of lpg - mutations and thus far rescued 7 different genes. These have identified proteins involved in LPG biosynthesis, compartmentalization within the eukaryotic secretory pathway, and regulation. We are using these mutants and genes to 1) identify novel biochemical targets for chemotherapeutic attack, 2) to identify new cellular pathways, such a pathway for GPI anchor biosynthesis for glycans separate from that for proteins, and 3) to probe the role of LPG in more detail in parasite survival within both the fly and the macrophage. We are especially interested in understanding the role of LPG in manipulating host cell signal transduction, which is radically altered in Leishmania infections.

We have studied the process of drug resistance mediated by gene amplification, using antifolate inhibition as a paradigm. Leishmania are auxotrophic for folates and pteridines, and these studies have revealed many unanticipated complexities about the pteridine biosynthetic pathway, including a bi-functional dihydrofolate reductase-thymidylate synthase and a novel broad spectrum pteridine reductase (PTR1), a folate transporter (FT1) and a pteridine transporter (BT1). All these loci have been implicated in genomic rearrangements in vitro and in vivo, yielding important insights into genome plasticity and chromosome evolution. Significantly, PTR1 can metabolically bypass antifolate inhibition and we have shown recently that combined inhibition of PTR1 and DHFR-TS can result in effective parasite control. Unexpectedly, we showed that PTR1, through the provision of reduced pteridines such as tetrahydrobiopterin, was implicated in the resistance of Leishmania to oxidative stress. We are currently probing the relevance of this in vivo. Since pteridines are essential cofactors for NO synthase which is important in host cell resistance to Leishmania, we are also curious as to whether Leishmania actively manipulates host pteridine levels to survive.

To isolate genes involved in parasite virulence more generally, we have used transfection of avirulent lines (obtained after extensive growth in vitro) to identify several genes which restore virulence in mouse infection tests. These genes specifically affect the ability of the parasite to establish macrophage infections, and act genetically by multi-copy suppression. One of these, UBF1, encodes an ubiquitin-like protein fusion showing homology to several yeast proteins involved in DNA repair. This suggests that as in other pathogens, DNA repair plays an important role in resisting host defense mechanisms.

An exciting development has been the introduction of transposable element systems into the study of parasites. One example of this is shuttle mutagenesis, where we use the yeast Ty1 system to insert mini-transposons into parasite genes in vitro for scoring in vivo following transfection into the parasite. Recently we have been able to engineer Leishmania in which the Drosophila transposable element mariner is expressed and active, yielding parasite populations where nearly all exhibit at least one transposition event. With this system we have selected for inactivation of the DHFR-TS gene and obtained lpg- mutations, and selected for transcriptional gene fusions to a hygromycin resistance marker. We plan to develop this system in several ways: as an insertion element for generating large panels of homozygous mutants that can be screened for effects on virulence, and for making fusions to GFP for FACS selection of stage specific gene expression.

Other interests of the lab include studies of gene structure, transcription and regulation; artificial Leishmania chromosomes and regulatable expression vectors; basic parasite genetics; the use of gene knockouts as potential live vaccines in people; and molecular evolution of parasites and virulence.

Zhang, K., J. M. Pompey, F-F Hsu, P. Key, P. Bandhuvula, J.D. Saba, J. Turk, and S.M. Beverley (2007), “Redirection of sphingolipid metabolism towards ethanolamine synthesis in Leishmania”, EMBO J. 26:1094-1104.

Beverley, S. M., K. L. Owens, M. Showalter, C. L. Griffith, T. L. Doering, V. C. Jones, and M. R. McNeil (2005), “Identification of eukaryotic UDP-galactopyranose mutase (UGM/GLF) in microbial and metazoal pathogens”, Eukaryotic Cell 4:1147-1154.

Zhang, K., F-F. Hsu, D. A. Scott, R. Docampo, J. Turk, and S. M. Beverley (2005), “Leishmania salvage and remodelling of host sphingolipids in amastigote survival and acidocalcisome biogenesis”, Molecular Microbiology 55:1566-1578.

Beverley, S.M. & D.E. Dobson (2004), “Flypaper for parasites”, Cell 119:311-312.

Zaph, C., J. Uzonna, S.M. Beverley, and P. Scott (2004), “Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites”, Nature Medicine 10:1104-1109.  (see commentary:  Seder and Sacks “Memory may not need reminding”, Nature Medicine 10: 1045-1047).

Uzonna, J., G. Späth, S. M. Beverley, and P. Scott (2004), “Vaccination with phosphoglycan-deficient lpg2- knockout Leishmania major protects highly susceptible mice from virulent challenge”, J. Immunology 172:  3793-7.

Zhang, K., M. Showalter, J. Revollo, F-F. Hsu, J. Turk, and S.M. Beverley (2003), Sphingolipids are essential for differentiation but not growth in Leishmania”, EMBO J. 22: 6016-26.

Zufferey, R., S. Allen, T. Barron, D.R. Sullivan, P.W. Denny, I.C. Almeida, D.F. Smith, S. J. Turco, M.A.J. Ferguson, and S.M. Beverley (2003). "Ether phospholipids and glycosylinositolphospholipids (GIPLs) are not required for amastigote virulence nor for inhibition of macrophage activation by Leishmania major", J. Biol. Chem. 278: 44708-18.

Späth, G., L-F. Lye, H. Segawa, D. L. Sacks, S. J. Turco, and S. M. Beverley (2003), "Persistence without pathology in phosphoglycan-deficient Leishmania major", Science, 301:1241-3.

Späth, G., L. A. Garraway, S. J. Turco and S. M. Beverley (2003), "The role(s) of lipophosphoglycan (LPG) in the establishment of Leishmania major infections in mammalian hosts", Proc. Natl. Acad. Sci. U.S.A. 100: 9536-41.

Dobson, D.E., L. Scholtes, K. Valdez, D. R. Sullivan, B. J. Mengeling, S. Cilmi, S. J. Turco, and S. M. Beverley (2003), "Functional Identification of Galactosyltransferases (SCGs) required for species-specific modifications of the lipophosphoglycan (LPG) adhesin controlling Leishmania major-sand fly interactions", J. Biological Chemistry 278:15523-15531.

Beverley, S.M. (2003), "Trypanosomatid protozoan parasite genetics comes of age: Protozomics!", Nature Reviews Genetics 4:11-19.

Beverley, S.M. (2003), "Genetic and genomic approaches to the analysis of Leishmania virulence", in Molecular & Medical Parasitology, J. Marr, T. Nilsen and R. Komuniecki, editors, Academic Press, New York, pages 111-122.

Gourley, D.G., A.W. Schüttelkopf, G.A. Leonard, J. Luba, L.W. Hardy, S.M. Beverley and W.N. Hunter (2001), "Pteridine reductase correlates pterin metabolism with drug resistance in trypanosomatid parasites" Nature Struct. Biol.8: 521-525.

Cunningham, M.L, R. Titus, S.J. Turco and S.M. Beverley (2001), "Regulation of differentiation to the infective stage of the protozoan parasite Leishmania by tetrahydrobiopterin", Science 292: 285-7.

Gerald F. Späth, Linda Epstein, Ben Leader, Steven M. Singer, Herbert A. Avila, Salvatore J. Turco and Stephen M. Beverley, "Lipophosphoglycan (LPG) is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major", Proc. Natl. Acad. Sci. USA 97: 9258-9263.

Sacks, D.L., G. Modi, E. Rowton, G. Späth, L. Epstein, S.J. Turco and S.M. Beverley (2000), "The role of phosphoglycans in Leishmania-sand fly interactions", Proc. Natl. Acad. Sci. USA 97: 406-411.

Beverley, S.M., S.J. Turco (1998), "LPG and the identification of virulence genes in the protozoan parasite Leishmania", Trends in Microbiology 6: 35-40.

Gueiros-Filho, F.J., S.M. Beverley (1997), "Trans-kingdom transposition: mobilization of the Drosophila element mariner in the protozoan Leishmania", Science 276:1716-1719.

Beverley, S.M. (1996) "Hijacking the cell: parasites in the driver's seat" Cell 78: 787-789.

Descoteaux, A. L. Ya, S.J. Turco, S.M. Beverley (1995), "A specialized pathway affecting virulence glycoconjugates in Leishmania", Science 269:1869-1872.

Titus, R.G., F.J. Gueiros-Filho, L.A.R de Freitas, S.M. Beverley (1995), "Development of safe live Leishmania vaccine lines by gene replacement", Proc. Natl. Acad. Sci. USA 92:10267-10271.

Bello, A.R., B. Nare, D. Freedman, L. Hardy, S.M. Beverley (1994), "PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate-resistance in the protozoan Leishmania major", Proc. Natl. Acad. Sci. USA 91:11442-11446.

Fernandes, A.P., K. Nelson, S.M. Beverley (1993), "Evolution of nuclear ribosomal RNAs in kinetoplastid protozoa: Perspectives on the age and origins of parasitism", Proc. Natl. Acad. Sci. USA 90:11608-12.

LeBowitz, J.H., H.Q. Smith., L. Rusché, S. M. Beverley (1993). "Coupling of poly(A) site selection and trans-splicing in Leishmania." Genes & Development 7: 996-1007.

Beverley, S.M., "Gene amplification in Leishmania" (1991), Annu. Rev. Microb. 45: 417-44.

Cruz, A., Beverley, S.M. (1990), "Gene replacement in parasitic protozoa", Nature 348: 171-4.

CV

Publications ( icon links to PDF file of publication.)

Published (or in press)

176. Scott, D. A., S. M. Hickerson, T. J. Vickers, and S. M. Beverley (2008), "The role of the mitochondrial glycine cleavage complex in the metabolism and virulence of the protozoan parasite Leishmania major", J. Biol. Chem. 283:155-165.
     

175. Capul, A.A., S. Hickerson, T. Barron, S. J. Turco, and S. M. Beverley (2007), "Comparisons of mutants lacking the Golgi UDP-Galactose or GDP-Mannose transporters establish that phosphoglycans are important for promastigote but not amastigote virulence in Leishmania major", Infection & Immunity 75: 4629-4637.
     

174. Hsu, F-F, Turk, J., Zhang, K. and S. M. Beverley (2007), "Characterization of Inositol Phosphorylceramides from Leishmania major by tandem mass spectrometry with electrospray ionization", J. Am. Soc. Mass Spectrometry 18: 1591-1604.
     

173. Capul, A.A., T. Barron, D. E. Dobson, S. J. Turco, and S. M. Beverley (2007), "Two functionally divergent UDP-Gal nucleotide-sugar transporters participate in phosphoglycan synthesis in Leishmania major", J. Biological Chemistry 282: 14006-14017.
     

172. Zhang, K., J. M. Pompey, F-F Hsu, P. Key, P. Bandhuvula, J.D. Saba, J. Turk, and S.M. Beverley (2007), "Redirection of sphingolipid metabolism towards ethanolamine synthesis in Leishmania", EMBO J. 26:1094-1104.
     

171. Myskova, J., M. Svobodova, M., S.M. Beverley, and P. Volf (2007), "An LPG-independent adherence paradigm for Leishmania - sand fly interactions in permissive vectors", Microbes & Infection 9:317-324.
     

170. Vickers, T.J., G. Orsomando, R. D. de la Garza, D. A. Scott, S. O. Kang, A.D. Hanson and S. M. Beverley (2006), "Biochemical and genetic analysis of methylenetetrahydrofolate reductase in Leishmania metabolism and virulence", J. Biological Chemistry 281: 38150-38158.

169. Dobson, D.E., L. D. Scholtes, P. J. Myler, S.J. Turco, and S. M. Beverley (2006), “Telomeric and internal clusters of the expanded SCG gene family associated with developmental and species-specific LPG modifications in Leishmania major”, Molecular & Biochemical Parasitology 146: 231-241.

168. Goswami, M., D. E. Dobson, S. M. Beverley & S. J. Turco (2006), “Demonstration by Heterologous Expression that the Leishmania SCA1 Gene encodes an Arabinopyranosyltransferase” Glycobiology 16:230-236.

167. Kébaïer, C., J.E. Uzonna, S.M. Beverley, and P. Scott (2005), “The presence of persistent attenuated Leishmania major parasites is not sufficient to provide protective immunity in C57BL/6 mice”, Infection & Immunity 74: 77-80. 166.

166. Schüttelkopf, A.W., L. W. Hardy S. M. Beverley and W.N. Hunter (2005), “Structures of Leishmania major pteridine reductase complexes reveal the active site features important for ligand binding and to guide structure-based inhibitor design”, J. Mol. Biol. 352: 105-116.

165. Ivens, A.C., (50+ authors, including S.M. Beverley), & P. J. Myler, “The genome of the kinetoplastid parasite Leishmania major” (2005), Science 309:436-442.

164. Casagrande, L., J.C. Ruiz, S.M. Beverley, & A. K. Cruz (2005), “Identification of DNA fragments which increase mitotic stability of linear episomal DNAs in Leishmania major“, International Journal for Parasitology 35: 973-980.

163. Beverley, S. M., K. L. Owens, M. Showalter, C. L. Griffith, T. L. Doering, V. C. Jones, and M. R. McNeil (2005) “Identification of eukaryotic UDP-galactopyranose mutase (UGM/GLF) in microbial and metazoal pathogens”, Eukaryotic Cell 4:1147-1154.

162. Segawa, H., R. Soares, M. Kawakita, S.M. Beverley and S. J. Turco (2005), “Reconstitution of GDP-Man Transport Activity with Purified Leishmania LPG2 Protein in Proteoliposomes”, J. Biol. Chem. 280: 2028 -2035.

161. Zhang, K., F-F. Hsu, D. A. Scott, R. Docampo, J. Turk, and S. M. Beverley (2004), "Salvage and remodeling of host sphingolipids in Leishmania amastigote survival and acidocalcisome biogenesis", Molecular Microbiology (in press).

160. Beverley, S.M. & D.E. Dobson (2004), "Flypaper for parasites", Cell 119:311-312.

159. Boulanger, N., C. Lowenberger, P. Volf, R. Ursic, L. Sigutova, L. Sabatier, M. Svobodova, R. Brun, G. Späth, S.M. Beverley, S. Perrotey, B. Pesson, and P. Bulet (2004), "Characterization of a defensin from the sand fly Phlebotomus duboscqi induced by challenge with bacteria or the protozoan parasite Leishmania major", Infection & Immunity (in press).

158. Zaph, C., J. Uzonna, S.M. Beverley, and P. Scott (2004), "Central memory T cells mediate long-term immunity to Leishmania major in the absence of persisent parasites", Nature Medicine 10:1104-1109. (see commentary: Seder and Sacks "Memory may not need reminding", Nature Medicine 10: 1045-1047).

157. Späth, G. L-F. Lye, H. Segawa, S. J. Turco, and S. M. Beverley (2004), "Identification of a compensatory mutant ( lpg2-REV ) in Leishmania major able to survive as amastigotes within macrophages without LPG2-dependent glycoconjugates, and its significance to virulence and immunization strategies", Infection & Immunity 72:3622-3627.

156. Akopyants, N.S., R. S. Matlib, B. H. Brownstein, G. D. Stormo, and S. M. Beverley (2004), "Expression profiling using a random genomic DNA microarray identifies differentially expressed genes associated with three major developmental stages of the protozoan parasite Leishmania major", Molec. Biochem. Parasitol. 136:71-86.

155. Zhang, K., T. Barron, S.J. Turco, and S.M. Beverley (2004), "The LPG1 family of Leishmania major" Molec. Biochem. Parasitol. 136: 11-23.

154. Uzonna, J., G. Späth, S. M. Beverley, and P. Scott (2004), "Vaccination with phosphoglycan-deficient lpg2- knockout Leishmania major protects highly susceptible mice from virulent challenge", J. Immunology172: 3793-7.

153. Duncan, R., P. Salotra, N. Goyal, N. Akopyants, S.M. Beverley, and H. Nakhasi (2004), "The application of gene expression microarray technology to Kinetoplastid research", Current Molecular Medicine 4: 611-621.

152. Zhang, K., M. Showalter, J. Revollo, F-F. Hsu, J. Turk, and S.M. Beverley, "Sphingolipids are essential for differentiation but not growth in Leishmania", EMBO J.22:6016-26.

151. Zufferey, R., S. Allen, T. Barron, D.R. Sullivan, P.W. Denny, I.C. Almeida, D.F. Smith, S. J. Turco, M.A.J. Ferguson, and S.M. Beverley (2003). "Ether phospholipids and glycosylinositolphospholipids (GIPLs) are not required for amastigote virulence nor for inhibition of macrophage activation by Leishmania major", J. Biol. Chem. 278: 44708-18.

150. Späth, G., L-F. Lye, H. Segawa, D. L. Sacks, S. J. Turco, and S. M. Beverley (2003), "Persistence without pathology in phosphoglycan-deficient Leishmania major", Science, 301:1241-3.

149. Späth, G., L. A. Garraway, S. J. Turco and S. M. Beverley (2003), "The role(s) of lipophosphoglycan (LPG) in the establishment of Leishmania major infections in mammalian hosts", Proc. Natl. Acad. Sci. U.S.A. 100: 9536-41.

148. Marchini, J.F.M., A.K. Cruz, S.M. Beverley, and L.R.O. Tosi (2003), "The H region HTBF gene mediates terbinafine resistance in Leishmania major", Molec. Biochem. Parasitol. 131:77-81.

147. Goyard, S. H. Segawa, J. Gordon, M. Showalter, R. Duncan, S. J. Turco and S. M. Beverley (2003), An in vitro system for differentiation and genetic studies of Leishmania donovani phosphoglycans, Molec. Biochem. Parasitol.130: 31-42.

146. Dobson, D.E., B. J. Mengeling, S. Cilmi, S. J. Turco, and S. M. Beverley (2003), Identification genes encoding the arabinosyl transferases (SCA) mediating developmental modifications of lipophosphoglycan (LPG) required for sand fly transmission of Leishmania major, J. Biol. Chem. 278: 28840-28848.

145. Coelho, A.C., S.M. Beverley and P.C. Cotrim (2003), Functional genetic identification of PRP1, an ABC transporter superfamily member conferring pentamidine resistance in Leishmania, Molec. Biochem. Parasitol. 130: 83-90.

144. Robinson, K.A., S. Goyard, and S. M. Beverley (2003), in vitro shuttle mutagenesis using engineered Mariner transposons, in Methods in Molecular Biology, Sarah Melville, Editor; Humana Press (in press).

143. Robinson, K.A. and S. M. Beverley (2003), "Improvements in transfection efficiency and tests of RNA interference (RNAi) approaches in the protozoan parasite Leishmania ", Molec. Biochem. Parasitol. 128: 217-228.

142. Atreya, C.E., E. F. Johnson, J.J. Irwin, A. Dow, K. M. Massimine,.I. Coppens, V. Stempliuk, S.M. Beverley, K.A. Joiner, B. K.Shoichet, and K. S. Anderson (2003), "A Molecular Docking Strategy Identifies Eosin B as a Non-Active Site Inhibitor of Protozoal Bifunctional Thymidylate Synthase-Dihydrofolate Reductase", J. Biological Chemistry 278: 14092-14100.

141. Dobson, D.E., L. Scholtes, K. Valdez, D. R. Sullivan, B. J. Mengeling, S. Cilmi, S. J. Turco, and S. M. Beverley (2003), "Functional Identification of Galactosyltransferases (SCGs) required for species-specific modifications of the lipophosphoglycan (LPG) adhesin controlling Leishmania major-sand fly interactions", J. Biological Chemistry 278: 15523-15531.

140. Beverley, S.M. (2003), "Protozomics: Trypanosomatid parasite genetics comes of age", Nature Reviews Genetics 4:11-19.

139. Gao, L-Y., R. Groger, J. Cox, S.M. Beverley, E. Lawson, and E. J. Brown (2003), "Transposon mutagenesis of Mycobacterium marinum reveals a link between pigmentation and intracellular survival", Infection & Immunity 71: 922-29.

138. Amaral, V.F., R. Porrozzi, A. Teva, M.P. Oliveira-Neto, A.J. Silva, M.S. Pereira, E. Cupolillo, S.G. Cotinho, C. Pirmez, S.M. Beverley and G. Grimaldi Jr. (2002), "Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania major vaccines in a Rhesus Monkey (Macaca mulatta) model of the human disease", Memorias do Instituto Oswaldo Cruz 97: 1041-1048.

137. Lye, L-F, M. Cunningham, and S.M. Beverley (2002), "Characterization of quinonoid-Dihydropteridine Reductase (QDPR) from the lower eukaryote Leishmania major", J. Biol. Chem. 277: 38245-38253.

136. Descoteaux, A., H. A. Avila, K. Zhang, S.J. Turco, and S.M. Beverley, (2002) "Leishmania LPG3 encodes a GRP94 homolog required for phosphoglycan synthesis implicated in parasite virulence but not viability", EMBO J. 21: 1-12.

135. Breitling, R., S. Klingner, R. Pietrucha, A. Geyer, G. Ehrlich, N. Callewaert, A. Müller, K-H Gührs, R. Contreras, S.M. Beverley, and K. Alexandrov (2002), "Kinetoplastida as a novel platform for protein research and production", Protein Expression & Purification25: 209-218

134. Myler, P.J., S.M. Beverley, A.K. Cruz, D.E. Dobson, A.C. Ivens, P.D. McDonagh, R. Madhubala, S. Martinez-Calvillo, J.C. Ruiz, A. Saxena, E. Sisk, S.M. Sunkin, E. Worthey, S. Yan, and K.D. Stuart (2001), "The Leishmania genome project: new insights into gene organization and function", Med. Microbiol. Immunol. 190: 9-12.

133. Goyard, S., L.R.O. Tosi, J. Gouzova, J. Majors, and S.M. Beverley (2001), "New Mos1 mariner derivatives and transposition assays suitable for the recovery of gene fusions in vivo and in vitro", Gene 280: 97-105.

132. Späth, G.F. and S. M. Beverley (2001), "An LPG-independent method for isolation of infective Leishmania metacyclic promastigotes by density gradient centrifugation", Protein Expression & Purification 25: 209-218.

131. Beverley, S.M. (2003), "Genetic and genomic approaches to the analysis of Leishmania virulence", in Molecular & Medical Parasitology, J. Marr, T. Nilsen and R. Komuniecki, editors, Academic Press, New York, pages 111-122.

130. Beverley, S.M., N.S. Akopyants, S. Goyard, R.S. Matlib, J.L. Gordon, B.H. Brownstein, G.D. Stormo, E.N. Bukanova, C.T. Hott, F. Li, S. MacMillan, J.N. Muo, L.A. Schwertman, M.R. Smeds and Y. Wang (2002), "Putting the Leishmania genome to work: functional genomics by transposon trapping and expression profiling",Philosophical Transactions B of the Royal Society: Biological Sciences 357: 47-53.

129. Selva, E.M., K. Hong, G-H. Baeg, S.M. Beverley, S.J. Turco, N. Perrimon and U. HŠcker (2001), "Dual role of the fringe connection gene in both wingless and fringe-dependent signaling events", Nature Cell Biol. 3: 809-815.

128. Gourley, D.G., A.W. Schüttelkopf, G.A. Leonard, J. Luba, L.W. Hardy, S.M. Beverley and W.N. Hunter (2001), "Structure and mechanism of Leishmania pteridine reductase correlate pterin metabolism with antifolate drug resistance" Nature Structural Biol. 8: 521-525.

127. Sunkin, S.M., P. McDonagh, M.L. Cunningham, S.M. Beverley, K. Stuart and P.J. Myler (2001), "Conservation of the LD1 region in Leishmania includes DNA implicated in LD1 amplification", Molec. Biochem. Parasitol. 113: 315-321.

126. Cunningham, M.L, R. Titus, S.J. Turco and S.M. Beverley (2001), "Regulation of differentiation to the infective stage of the protozoan parasite Leishmania by tetrahydrobiopterin", Science 292: 285-7. Commentary:

125. Turco, S.J., Späth, G.F. and S.M. Beverley (2001), "Is Lipophosphoglycan (LPG) a Virulence Factor? A surprising diversity between Leishmania species", Trends in Parasitology 17: 223-226.

124. Cunningham, M.L. and S.M. Beverley (2001), "Pteridine salvage throughout the Leishmania infectious cycle and the implications for antifolate chemotherapy", Molec. Biochem. Parasitol. 113: 199-213.

123. Akopyants, N.S., S.W. Clifton, J. Martin, D. Pape, T. Wylie, T., L. Li, J.C. Kissinger, D.S. Roos, and S.M. Beverley (2001), "A Survey of the Leishmania major Friedlin strain VI genome by Shotgun Sequencing: A Resource for DNA Microarrays and expression profiling", Molec. Biochem. Parasitol. 113: 337-400.

122. Streit, J.A., T.J. Recker, F. Gueiros-Filho, S.M. Beverley, and M.E. Wilson (2000), "Protective immunity against the protozoan Leishmania chagasi is induced by subclinical cutaneous infectious with virulent but not avirulent organisms", J. Immunol..

121. Gehring, A.M., J.R. Nodwell, S.M. Beverley, and R.M. Losick (2000), "Genome wide insertional mutagenesis in Streptomyces coelicolor identifies additional genes involved in morphological differentiation", Proc. Natl. Acad. Sci. USA 97: 9642-7.

120. C.J. Coates, N. Jasinskiene, D. Morgan, L.R.O. Tosi, S.M. Beverley, A.A. James (2000) "Purified mariner (Mos1) transposase catalyzes the integration of marked elements into the germ-line of the yellow fever mosquito, Aedes aegypti." Insect Biochemistry and Molecular Biology 30: 1003-1008.

119. Gerald F. Späth, Linda Epstein, Ben Leader, Steven M. Singer, Herbert A. Avila, Salvatore J. Turco and Stephen M. Beverley, "Lipophosphoglycan (LPG) is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major", Proc. Natl. Acad. Sci. USA 97: 9258-9263.

118. Ben Mamoun, C., I.Y. Gluzman, S.M. Beverley and D.E. Goldberg (2000), "Transposition of the Drosophila element mariner within the human malaria parasite Plasmodium falciparum", Molec. Biochem. Parasitol. 110: 405-408.

117. Carrillo, M.B., W. Gao, W., M. Herrera, J. Moore, J. Alroy, S.M. Beverley, and M.A. Pereira (2000), "Heterologous expression of Trypanosoma cruzi trans-sialidase in Leishmania enhances virulence", Infection & Immunity 68: 2728-34.

116. Goyard, S. and S.M. Beverley (2000), "Blasticidin S resistance: a new independent dominant selectable marker for stable transfection of Leishmania", Molec. Biochem. Parasitol. 108: 249-252.

115. Tosi, L.R.O, and S. M. Beverley (2000), "cis and trans factors affecting Mos1 mariner transposition in vitro, and its application to functional genomics", Nucleic Acids Res 28: 784-790.

114. Hong, K., D. Ma, S.M. Beverley, and S.J. Turco (2000), "The Leishmania GDP-Mannose transporter is an autonomous, multi-specific, hexameric complex of LPG2 subunits", Biochemistry 39: 2013-2022.

113. Sacks, D.L., G. Modi, E. Rowton, G. Späth, L. Epstein, S.J. Turco and S.M. Beverley (2000), "The role of phosphoglycans in Leishmania-sand fly interactions", Proc. Natl. Acad. Sci. USA 97: 406-411.

112. Chakkalath, H.R., A.A. Siddiqui, A.H. Shankar, D.E. Dobson, S.M. Beverley, and R.G. Titus (2000), Priming of a b -galactosidase (b GAL)-specific type 1 response in BALB/c mice infected with b GAL-transfected Leishmania major", Infection & Immunity 68: 809-814.

111. Brodskyn, C., S.M. Beverley, and R.G. Titus (2000), "Immune response to avirulent Leishmania major (dhfr-ts-) by human cells using an in vitro system", Clinical and Experimental Immunology 119: 299-304.

110. Cotrim, P.C., L. K. Garrity, and S. M. Beverley (1999), "Isolation of genes mediating resistance to inhibitors of nucleoside and ergosterol metabolism in Leishmania by over-expression/selection", J. Biol. Chem. 274: 37723-37730.

109. Clayton, C, S. Ha, L. Rusché, C. Hartmann, and S. Beverley (2000), "Tests of heterologous promoters and intergenic regions in Leishmania major" Mol. Biochem. Parasitol. 105: 163-167.

108. Lemley, C., S. Yan, V.S. Dole, R. Madhubala, M.L. Cunningham, S.M. Beverley, P.J. Myler, and K.D. Stuart, "The Leishmania donovani LD1 locus gene ORFG encodes a biopterin transporter (BT1)" Molec. Biochem. Parasitol. 104: 93-105.

107. Cormack, B., B.T. Rouse, and S.M. Beverley (1999), "Host-microbe interactions: fungi/viruses/parasites. Editorial Overview: The emergence of protozoan microbiology", Current Opinions in Microbiology 2: 343-347.

106. D.Gourley, J. Luba, L.W. Hardy, S.M. Beverley, and W.N. Hunter (1999), "Crystallization of recombinant Leishmania major Pteridine Reductase 1 (PTR1)", Acta Crystallographica D Biol Crystallogr. 55: 1608-10.

105. Ben Mamoun, C., I.Y. Gluzman, S. Goyard, S.M. Beverley, and D.E. Goldberg (1999), "A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum", Proc. Natl. Acad. Sci. USA 96: 8716-8720.

104. Veras, P.S.T., C.I. Brodskyn, F. Balestieri, L.A.R. de Freitas, A.P.S. Ramos, A.R.P. Queiroz, A. Barral, S.M. Beverley and M. Barral-Netto (1999), "A dhfr-ts- Leishmania major knockout mutant cross-protects against Leishmania amazonensis", Memorias do Oswaldo Cruz 94: 491-496.

103. Wang, Y. K. Dimitrov, L.K. Garrity, S. Sazer, and S. M. Beverley (1998), "Stage-specific activity of the Leishmania major CRK3 kinase and functional rescue of a Schizosaccharomyces pombe cdc2 mutant", Mol. Biochem. Parasitol. 96: 139-150.

102. Vasudevan, G., N.S. Carter, M.E. Drew, S.M. Beverley, M.A. Sanchez, A. Seyfang, B. Ullman and S. Landfear (1998), "Cloning of Leishmania nucleoside transporter genes by rescue of a transport-deficient mutant", Proc. Natl. Acad. Sci. USA 95: 9873-9878.

101. Adams, M., R. Almeida, T. Baltz, M. Barrett, P. Bastien, S. Belli, S. Beverley, N. Biteau, J. Blackwell, C. Blaineau, M. Boshart, F. Bringaud, C. Clayton, A. Cruz, W. Degrave, J. Donelson, N. El-Sayed, G. Fu, K. Ersfeld, W. Gibson, K. Gull, A. Ivens, J. Kelly, D. Lawson, J. Lebowitz, P. Majiwa, K. Matthews, S. Melville, G. Merlin, P. Michels, P. Myler, A. Norrish, F. Opperdoes, B. Papadopoulou, M. Parsons, T. Seebeck, D. Smith, K. Stuart, M. Turner, E. Ullu, and L. Vanhamme (1998), "Genetic nomenclature for Trypanosoma and Leishmania", Mol. Biochem. Parasitol. 97: 221-224.

100. Descoteaux, A., B.J. Mengeling, S.M. Beverley, S.J. Turco (1998), "Leishmania donovani has distinct mannosylphosphoryltransferases for the initiation and elongation phases of lipophosphoglycan repeating unit biosynthesis", Mol. Biochem. Parasitol. 94: 27-40.

99. Luba, J.L., B. Nare, P-H. Liang, K.S. Anderson, S.M. Beverley, L.W. Hardy (1998), "Leishmania major pteridine reductase 1 (PTR1) belongs to the short chain dehydrogenase family: stereochemical and kinetic evidence", Biochemistry 37: 4093-4104.

98. Beverley, S.M., S.J. Turco (1998), "LPG and the identification of virulence genes in the protozoan parasite Leishmania", Trends in Microbiology 6: 35-40.

97. Hardy, L.W., W. Matthews, B. Nare, S.M. Beverley (1997), "Biochemical and genetic tests for inhibitors of Leishmania pteridine pathways" Experimental Parasitology 87: 157-169.

96. Mengeling, B.J., S.M. Beverley, S.J. Turco (1997), "Designing glycoconjugate biosynthesis for an insidious intent: phosphoglycan assembly in Leishmania parasites" Glycobiology 7: 873-880.

95. Gueiros-Filho, F.J., S.M. Beverley (1997), "Trans-kingdom transposition: mobilization of the Drosophila element mariner in the protozoan Leishmania", Science 276:1716-1719.

94. Garraway, L.A., L.R.O. Tosi, Y. Wang, J.B. Moore, D.E. Dobson, S.M. Beverley (1997), "Insertional mutagenesis using a modified in vitro Ty1 transposition system", Gene 198: 27-35.

93. Nare, B., L. Hardy, S.M. Beverley (1997), " New approaches to Leishmania chemotherapy: Pteridine Reductase 1 (PTR1) as a target and modulator of antifolate sensitivity", in Molecular Basis of Drug Design and Resistance, Coombs, G.H. and Croft, S.L. (eds), Parasitology 34: S102-S110, Cambridge University Press.

92. Nare, B., L. Hardy, S.M. Beverley (1997), "The roles of Pteridine Reductase 1 (PTR1) and Dihydrofolate Reductase-Thymidylate Synthase (DHFR-TS) in pteridine metabolism in Leishmania", J. Biol. Chem. 3883-3891.

91. Garcia, M.R., S. Graham, R.A. Harris, S.M. Beverley, P.M. Kaye (1997), "Epitope cleavage by Leishmania endopeptidase(s) limits the efficiency of the exogenous pathway of MHC class I associated antigen presentation", Eur. J. Immunol27:1005-1013.

90. Tosi, L.R.O., L. Casagrande, S.M. Beverley, A.K. Cruz (1997), "Physical mapping across the dihydrofolate reductase-thymidylate synthase chromosome of Leishmania major", Parasitology114:521-530.

89. Racoosin, E.L., S.M. Beverley (1997), "Leishmania major: Promastigotes induce expression of a subset of chemokine genes in murine macrophages", Experimental Parasitology 85: 283-295.

88. Beverley, S.M. (1996) "Hijacking the cell: parasites in the driver's seat" Cell, 78: 787-789.

87. Ma, D., D. Russell, S.M. Beverley, S.J. Turco, "Golgi GDP-Mannose Uptake Requires Leishmania LPG2: a Member of a Eukaryotic Family of Potential Nucleotide-sugar Transporters", J. Biol. Chem. , 272: 3799-3805.

86. Flaspohler, J.A., W.L. Rickoll, S.M. Beverley, M. Parsons (1996), "Common ancestry of glycosomes and peroxisomes revealed by functional identification of a Leishmania gene related to peroxisome assembly factor 1", Molec. Cell. Biol. 17: 1093-1101.

85. Beverley, S.M. (1995), "Identification of Leishmania genes by functional complementation: application to drug resistance and virulence", Memorias do Instituto Oswaldo Cruz 90(I):12-14.

84. Turco, S.J., S.M. Beverley (1997) "A genetic analysis of the biosynthetic pathway of the Leishmania virulence factor LPG", Trypanosomiasis and Leishmaniasis (G. Hide, J.C. Mottram, G.H. Coombs, P.H. Holmes, eds), CAB International, Glasgow, 79-88.

83. Ha, D.S., Schwarz, J.K., S.J. Turco, S.M. Beverley (1996), "Use of the green fluorescent protein as a marker in transfected Leishmania ", Molec. Biochem. Parasitol 77: 57-64.

82. Beverley, S.M., S.J. Turco (1995), "Identification of genes mediating lipophosphoglycan (LPG) biosynthesis by functional complementation of Leishmania donovani mutants", Annals Trop. Medicine & Parasitology 89: s11-18.

81. Ma, D., S.M. Beverley, S.J. Turco (1996), " Leishmania donovani possess a NADPH-dependent glyceryl ether monooxygenase " Biochem. Biophys. Res. Commun. 227:885-889.

80. Gueiros-Filho, F.J., S.M. Beverley (1996), "Selection against Dihydrofolate Reductase-Thymidylate Synthase ( DHFR-TS ) as a probe of genetic alterations in Leishmania ". Molec. Cell. Biol. 16:5655-5663.

79. Descoteaux, A. L. Ya, S.J. Turco, S.M. Beverley (1995), "A specialized pathway affecting virulence glycoconjugates in Leishmania ", Science 269:1869-1872.

78. Cupolillo, E., G. Grimaldi Jr., H. Momen, S.M. Beverley (1995), "Intergenic Region Typing (IRT): a rapid molecular approach to the characterization and evolution of Leishmania", Molec. Biochem. Parasitol. 73:145-155.

77. Titus, R.G., F.J. Gueiros-Filho, L.A.R de Freitas, S.M. Beverley (1995), "Development of safe live Leishmania vaccine lines by gene replacement", Proc. Natl. Acad. Sci. USA 92:10267-10271.

76. Callahan, H.L., W.L. Roberts, P. M. Rainey, S.M. Beverley (1994), "The PGPA gene of Leishmania major mediates antimony (SbIII) resistance by decreasing influx and not by increasing efflux ", Mol. Bioch. Parasitol. 68: 145-150.

75. Bello, A.R., B. Nare, D. Freedman, L. Hardy, S.M. Beverley (1994), "PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate-resistance in the protozoan Leishmania major", Proc. Natl. Acad. Sci. USA 91:11442-11446.

74. Turco, S.J., A. Descoteaux, K. Ryan, L.A. Garraway, S.M. Beverley (1994), "Isolation of virulence genes directing GPI synthesis by functional complementation of Leishmania", Brazilian J. Med. Biol. Res. 27: 133-138.

73. Pimenta, Paulo F.P., E.M.B. Saraiva, E. Rowton, G.B. Modi, L.A. Garraway, S.M. Beverley, S.J. Turco, D.L. Sacks (1994), "Evidence that the vectorial competence of phlebotomine sand flies for different species of Leishmania is controlled by structural polymorphisms in the surface lipophosphoglycan", Proc. Natl. Acad. Sci. USA 91:9155-9159.

72. Gueiros-Filho, F.J., S.M. Beverley (1994), "On the introduction of genetically modified Leishmania outside the laboratory", Exp. Parasitol. 78:425-428.

71. Fernandes, A.P., K. Nelson, S.M. Beverley (1993), "Evolution of nuclear ribosomal RNAs in kinetoplastid protozoa: Perspectives on the age and origins of parasitism", Proc. Natl. Acad. Sci. USA 90:11608-11612.

70. Freedman, D.F., S.M. Beverley (1993), "Two additional independent markers for transfection of Leishmania", Mol. Biochem. Parasitology 62: 37-44.

69. Descoteaux, A., L.A. Garraway, K.A. Ryan, L. K. Garrity, S.J. Turco, S.M. Beverley (1994), "Functional complementation of virulence genes in the protozoan parasite Leishmania", Methods in Molecular Genetics , K.W. Adolph ed., Vol 1, pp. 22-48.

68. Ryan, K.A., L.A. Garraway, A. Descoteaux, S.J. Turco, S.M. Beverley (1993). "Identification of virulence genes directing surface GPI biosynthesis in protozoan parasites", Proc. Natl. Acad. Sci. USA 90: 8609-8613.

67. Medina-Acosta, E., S.M. Beverley, D.G. Russell (1993). "Evolution and expression of the Leishmania surface protease (gp63) gene locus", Infectious Agents and Disease 2:25-34.

66. Kaye, P.M., C. M. Coburn, M. McCrossan, S.M. Beverley (1993). "Antigens targeted to the Leishmania phagolysosome are processed for CD4+ T-cell recognition". Eur. J. Immunol. 23:2311-2319.

65. Ryan, K.A., S. Dasgupta, S.M. Beverley, (1993), "Shuttle cosmid vectors for the trypanosomatid parasite Leishmania", Gene 131:145-50.

64. Garber, D.A., S.M. Beverley, D.M. Coen (1993), "Demonstration of circularization of Herpes Simplex virus DNA following infection using pulsed field electrophoresis" Virology 197: 459-462.

63. LeBowitz, J.H., H.Q. Smith., L. Rusch*, S. M. Beverley (1993). "Coupling of poly(A) site selection and trans -splicing in Leishmania. " Genes & Development 7: 996-1007.

62. Callahan, H.L., S.M. Beverley (1992). "A member of the aldoketo-reductase family confers methotrexate resistance in Leishmania. " J. Biol. Chem.. 267: 24165-24168.

61. Uliana, S.R.B., K. Nelson, S.M. Beverley, E.P. Camargo, L.M. Floeter-Winter (1994). "Discrimination amongst Leishmania by PCR amplification and hybridization with SSU rRNA-derived oligonucleotides." J. Eukaryotic Genetics 41:324-330.

60. Lo´pez, J.A., J.H. LeBowitz, S.M. Beverley, H-G. Rammensee, P. Overath (1992). "Leishmania mexicana promastigotes induce cytotoxic T lymphocytes in vivo that do not recognize infected macrophages ". Eur. J. Immunol. 23: 217-223.

59. Cruz, A.K., R. Titus, S.M. Beverley (1993). "Plasticity in chromosome number enables testing of essential genes in Leishmania by targeting." Proc. Natl. Acad. Sci. USA 90: 1599-1602.

58. Wilson, K., S.M. Beverley, B. Ullman (1992). Stable amplification of a linear extrachromosomal DNA in mycophenolic acid-resistant Leishmania donovani. Molec. Biochem. Parasitol. 55: 197-206.

57. Hanson, S., S.M. Beverley, W. Wagner, B. Ullman (1992). Unstable Amplification of two extrachromosomal elements in (-difluoromethylornithine-resistant Leishmania donovani. Molec. Cell. Biol 12: 5499-5507.

56. Briones, M.R.S., K. Nelson, S.M. Beverley, H.T. Affonso, E.P. Camargo, L.M. Floeter-Winter (1992), "Leishmania tarentolae taxonomic relatedness inferred from phylogenetic analysis of small subunit ribosomal RNA genes", Molec. Biochem. Parasitol. 53:121-128.

55. LeBowitz, J.H., A. Cruz, S.M. Beverley (1991), "Thymidine kinase as a negative selectable marker in Leishmania major", Molec. Bioch. Parasit. 51:321-326.

54. Cruz, A.C., C.M. Coburn, S.M. Beverley. (1991). Double targeted gene replacement in Leishmania major . Memorias do Instituto Oswaldo Cruz, Vol. 86 Suppl I, 9-10.

53. Beverley, S.M, C.E. Clayton CE (1993). Transfection of Leishmania and Trypanosoma brucei by electroporation. In: Hyde JE, ed. Protocols in Molecular Parasitology, Methods in Molecular Biology Vol 21, New Jersey: Humana Press, p. 333-348.

52. Callahan, H.L., S.M. Beverley (1991), "Heavy metal resistance: a new role for P-glycoproteins in Leishmania", J. Biol. Chem. 266: 18427-18430.

51. Cruz, A., C.M. Coburn, S.M. Beverley (1991), "Double targeted gene replacement for creating null mutants", Proc. Natl. Acad. Sci. USA 88:7170-7174.

50. McMahon-Pratt, D., Traub-Cseko, Y., Lohman, K., Rogers, D.D., Beverley, S.M. (1992), "Loss of the GP46/M-2 surface membrane glycoprotein gene family in the Leishmania braziliensis complex", Molec. Bioch. Parasitol. 50:151-160.

49. LeBowitz, J.H., C.M. Coburn, S.M. Beverley (1991), "Simultaneous transient expression assays adapted for the trypanosomatid parasite Leishmania using beta-galactosidase and beta-glucuronidase as reporter enzymes", Gene 103:119-123.

48. Beverley, S.M., "Gene amplification in Leishmania " (1991), Annu. Rev. Microb. 45: 417-44.

47. Coburn, C.M., Otteman, K., McNeely, T.B., Turco, S.J., Beverley, S.M. (1991), "Stable DNA Transfection of a wide range of trypanosomatids", Mol. Bioch. Parasit. 46: 169-179.

46. Panton, L.J., Tesh, R.B., Nadeau, K.C., Beverley, S.M. (1991), "A test for genetic exchange in mixed infections of Leishmania major in the sand fly Phlebotomus papatasi", J. Protozoology 38:224-228.

45. Cruz, A., Beverley, S.M. (1990), "Gene replacement in parasitic protozoa", Nature 348: 171-4.

44. LeBowitz, J.H., Coburn, C.M., McMahon-Pratt, D., Beverley, S.M. (1990), "Development of a stable Leishmania expression vector and application to the study of parasite surface antigen genes", Proc. Natl. Acad. Sci. USA 87: 9736-40.

43. Beverley, S.M., C.M. Coburn, G.M. Kapler (1991), "High-efficiency stable DNA transformation of the human parasite " Leishmania major, The Biology of Parasitism, C.C. Wang, Ed., American Society for the Advancement of Science, p. 139-146.

42. Nelson,K., G. Alonso, P.J. Langer, S.M. Beverley (1990) Sequence of the Dihydrofolate reductase-thymidylate synthase gene of Leishmania amazonensis. Nucleic Acids Research 19: 2819 (for the record).

41. Kapler, G.M., K. Zhang, S.M. Beverley (1990), "Nuclease mapping and DNA sequence analysis of transcripts from the dihydrofolate reductase-thymidylate synthase (R) region of Leishmania major ", Nucleic Acids Research 18:6399-6408.

40. Swafford, J.R., S.M. Beverley, C.C. Kan, J.P. Caulfield (1990), "Distribution of dihydrofolate reductase-thymidylate synthase polypeptide in methotrexate resistant and wild-type Leishmania major . Evidence for cytoplasmic distribution despite a hydrophilic leader sequence", Proceedings of the XIIth International Congress of Electron Microscopy, p. 610-611.

39. Beverley, S.M., C.M. Coburn (1990), "Recurrent de novo appearance of small linear DNAs in Leishmania major and relationship to extra-chromosomal DNAs observed in other species", Molec. Biochem. Parasitol. 42: 133-141.

38. Beverley, S.M. (1990), "Enzymatic amplification of RNA by Polymerase Chain Reaction", in Ausubel, F., Brent, R., Kingston, R., Moore, D., Seidman, J., Smith, J.A., and Struhl, K., Current Protocols in Molecular Biology , Greene Publishing Associates, New York., pages 15.4.1-15.4.6.

37. Kapler, G.M., Coburn, C.C. and Beverley, S.M. (1990), "Stable Transfection of the human parasite Leishmania delineates a 30 kb region sufficient for extra-chromosomal replication and expression", Molec. Cell. Biol. 10:1084-1094.

36. Lopes, A.H. de C.S., Iovannisci, D., Petrillo-Peixoto, M., McMahon-Pratt, D. and Beverley, S.M. (1990), "Evolution of nuclear DNA and the occurrence of sequences related to new small chromosomal DNAs in the trypanosomatid genus " Endotrypanum, Molec. Bioch. Parasitology 40: 151-162.

35. Ellenberger, T.E., Wright, J.E., Rosowsky, A. and Beverley, S.M. (1989), "Wild-type and drug-resistant Leishmania major hydrolyze methotrexate to N-10-methyl-4-deoxy-4-aminopteroate without accumulation of methotrexate polyglutamates", J. Biol. Chem. 264: 15960-15966.

34. Kapler, G.M. and Beverley, S.M. (1989), "Transcriptional mapping of the amplified region encoding the dihydrofolate reductase-thymidylate synthase of Leishmania major reveals a high density of transcripts, including overlapping and antisense RNAs", Molec. Cell. Biol. 9: 3959-3972.

33. Ellenberger, T.E. and Beverley, S.M. (1989), "Multiple drug resistance linked to conservative amplification of the H region in Leishmania major", J. Biol. Chem. 264: 15094-15103.

32. Iovannisci, D.M. and Beverley, S.M. (1989), "Structural alterations of chromosome 2 in Leishmania major as evidence for diploidy, including spontaneous amplification of the mini-exon array". Molec. Bioch. Parasitology 34: 177-188.

31. Petrillo-Peixoto, M.L. and Beverley, S.M. (1989), "Amplification of a new region of DNA in an unselected laboratory stock of Leishmania tarentolae: the T region", J. Protozoology 36: 257-261.

30. Beverley, S.M. (1989), "Estimation of circular DNA size using gamma-irradiation and pulsed field electrophoresis", Anal. Biochem. 177: 110-114.

29. Beverley, S.M. and Petrillo-Peixoto, M.L. (1988). Naturally-occurring gene amplifications conferring drug resistance in Leishmania tarentolae. Memorias do Instituto Owaldo Cruz , Vol. 83, Suppl. I, p. 330-333.

28. Petrillo-Peixoto, M.L. and S.M. Beverley (1988). Amplified DNAs in laboratory stocks of Leishmania tarentolae: extrachromosomal circles structurally and functionally similar to the inverted H region amplification of methotrexate-resistant L. major. Molec. Cell. Biol. 8:5188-5199.

27. Beverley, S.M., Ellenberger, T.E. and Petrillo-Peixoto, M. L. (1989), "Unstable and stable gene amplification in methotrexate-resistant Leishmania major and natural isolates of Leishmania tarentolae, Leishmaniasis: The Current Status and New Strategies for Control ", D.T. Hart, Ed., Plenum Press, New York p. 873-878.

26. Beach, D.H., Goad, L.J., Berman, J.D., Ellenberger, T.E., Beverley, S.M., Holz, G.G., Jr. (1989), "Effects of a squalene-2,3-epoxidase inhibitor on propagation and sterol biosynthesis of Leishmania promastigotes and amastigotes", in Leishmaniasis: The current status and New Strategies for Control, D.T. Hart, Ed., Plenum Press, New York, p. 885-890.

25. Beverley, S.M. (1988), "Characterization of the "unusual" mobility of large circular DNAs in pulsed field-gradient electrophoresis", Nucleic Acids Res. 16:925-938.

24. Beverley, S.M., Ellenberger, T.E., Iovannisci, D.M., Kapler, G.M., Petrillo-Peixoto, M., Sina, B.J. (1988), "Gene amplification in Leishmania ", Englund, P.T., and Sher, A., Biology of Parasitism , MBL Lectures in Biology, Vol 9. Alan Liss, Publishers, pp 431-448.

23. Petrillo Peixoto, M., Beverley, S.M. (1987), "In vitro activity of sulfonamides and sulfones on promastigotes of Leishmania major ", Antimicrobial Agents and Chemotherapy 31: 1575-8.

22. Ellenberger, TE, Beverley, SM (1987), "Biochemistry and regulation of folate and methotrexate transport in Leishmania major", J. Biol. Chem. 262: 10053-58.

21. Ellenberger, TE, Beverley, SM (1987), "Reductions in methotrexate and folate uptake in methotrexate-resistant lines of Leishmania major are independent of gene amplification" J. Biol. Chem. 262: 13501-13506.

20. Beverley, S.M., Ismach, R.B., McMahon-Pratt, D. (1987), "Evolution of the genus Leishmania as revealed by comparisons of nuclear DNA restriction fragments", Proc. Natl. Acad. Sci. USA 84: 484-488.

19. Kapler, G.M., Zhang, K., Beverley, S.M. (1987), "Sequence and S1 nuclease mapping of the 5' region of the dihydrofolate reductase-thymidylate synthase gene of Leishmania major, Nucleic Acids Research " 15: 3369-3383.

18. Beverley, S.M., Ismach, R.B., McMahon-Pratt, D. (1986), "Evolution of the genus Leishmania Ross (1903) as revealed by comparisons of nuclear DNA restriction fragment patterns", in Rioux, J.-A., Leishmania: Taxonomy and Phylogeny Applications to Ecology and Epidemiology Proceedings of International colloquium at Montpellier July 2-6 1984 . Institut Mediterranean D'Etudes Epidemiologique et Ecologiques Press, Montepellier, p. 265-267.

17. Beverley, S.M., Ellenberger, T.E., Cordingley, J.S. (1986), "Primary structure of the gene encoding the bifunctional dihydrofolate reductase-thymidylate synthase of Leishmania major", Proc. Natl. Acad. Sci USA 83: 2585- 2588.

16. Beverley, S.M. and A.C. Wilson (1985), "Ancient Origin for Hawaiian Drosophilinae Inferred from Protein Comparisons", Proc. Natl. Acad. Sci. USA 82: 4800-4804.

15. Beverley, S.M., J.A. Coderre, D.V. Santi and R.T. Schimke (1984), "Unstable DNA Amplifications in Methotrexate- resistant Leishmania Consist of extra-chromosomal circles which relocalize during stabilization", Cell , 38: 431-9.

14. Federspiel, N.A., S.M. Beverley, J. Schilling, R.T. Schimke (1984), "Novel DNA rearrangements are associated with dihydrofolate reductase gene amplification", J. Biol. Chem. 259: 9127-9140.

13. Beverley, S.M. and A.C. Wilson (1984), "Molecular Evolution in Drosophila and the Higher Diptera, II: A Time Scale for Dipteran Evolution", J. Molec. Evol. 21: 1-13.

12. Garrett, C.E., J.A. Coderre, T.D. Meek, E.P. Garvey, D.M. Claman, S.M. Beverley and D.V. Santi (1983), "A Bifunctional Thymidylate Synthase-Dihydrofolate Reductase in Protozoa", Molec. Bioch. Parasitology. 11: 257-265.

11. Coderre, J.A., S.M. Beverley, R.T. Schimke and D.V. Santi (1983), "Overproduction of a Bifunctional Thymidylate Synthase-Dihydrofolate Reductase and DNA Amplification in Methotrexate-Resistant Leishmania tropica", Proc. Natn. Acad. Sci. USA 80: 2132-2136.

10. Johnston, R.N., S.M. Beverley and R.T. Schimke (1983), "Rapid spontaneous dihydrofolate reductase gene amplification shown by fluorescence-activated cell sorting", Proc. Natn. Acad. Sci. 80: 3711-3715.

9. Schimke, R.T., S.M. Beverley, P.C. Brown, R. Cassin, N. Federspiel, C. Gasser, A. Hill, R. Johnston, B., E. Mosse, H. Rath, D. Smouse and T. Tlsty (1983), "Drug Resistance and Gene Amplification in Eukaryotic Cells", in Singer, T.P. and R.N. Ondarza, Mechanism of Drug Action , Academic Press, New York, p 107-117.

8. Santi, D.V., J.A. Coderre, S.M. Beverley and R.T. Schimke (1983), "Methotrexate-Resistant Leishmania tropica: A Model for Drug Resistance in Pathogenic Protozoa", Third John Jacob Abel Symposium on Drug Development: Molecular Parasitology, Academic Press, p. 107-121.

7. Schimke, R.T., S.M. Beverley, P.C.Brown, R. Cassin, N. Federspiel, C.Gasser, A. Hill, R. Johnston, B. Mariani, E. Mosse, H. Rath, D. Smouse and T. Tlsty (1983), "Gene Amplification and Drug Resistance in Cultured Animal Cells", in Cancer Treatment Reviews (International Symposium at Regensburg, FRG).

6. Beverley, S.M. and A.C. Wilson (1982), "Molecular Evolution in Drosophila and the Higher Diptera: I. Micro- complement Fixation Studies of a Larval Hemolymph Protein", J. Molec. Evol. 18: 251-264.

5. Schilling, J., S.M. Beverley, C. Simonsen, G. Crouse, D. Setzer, J. Feagin, M. McGrogan, N. Kohlmiller, R.T. Schimke (1982), "Dihydrofolate reductase gene structure and variable structure of amplified DNA in mouse cell lines", in R.T. Schimke, ed., Gene Amplification , Cold Spring Harbor Laboratory, p. 149 - 154.

4. Brown, P.C., S.M. Beverley and R.T. Schimke (1981), "Relationship of Amplified Dihydrofolate Reductase Genes to Double Minute Chromosomes in Unstably Resistant Mouse Fibroblast Cell Lines", Molec. Cell. Biology 1: 1077- 1083.

3. Haber, D.A., S.M. Beverley, M. Kiely and R.T. Schimke (1981) "Properties of an Altered Dihydrofolate Reductase Encoded by Amplified Genes in Cultured Mouse Fibroblasts", J. Biol. Chem. 256: 9501-9510.

2. Zimmer, E.A., S.L. Martin, S.M. Beverley, Y.W. Kan and A.C. Wilson (1980), "Rapid Duplication and Loss of Genes Coding for the Alpha Chain of Hemoglobin", Proc. Natn. Acad. Sci. 77: 2158-2162.

1. Beverley, S.M. (1979), "Molecular Evolution in Drosophila and the Higher Diptera", Ph.D. Thesis, University of California, Berkeley, 424 pp.

Patents