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publications, contact information

Brindley laboratory

Paul Brindley is a research scientist and professor with national and international research experience (> 150 peer reviewed publications). He has held scientific and academic appointments at the National Institutes of Health in Bethesda, Maryland, USA, the Queensland Institute of Medical Research in Brisbane, Australia, University College, Dublin, Ireland, Tulane University Health Sciences Center, New Orleans, Louisiana, and George Washington University (GWU), Washington, DC.

Research themes in the Brindley laboratory at GWU focus on helminth parasites that infect people. More specifically, ongoing projects deal with basic molecular aspects of the genome, proteome and biochemistry of the human schistosomes, including development of transgenic parasites, and the molecular pathogenesis of liver fluke induced liver cancer (Opisthorchis viverrini associated cholangiocarcinoma).

Our research is primarily laboratory-based, but also involves evolutionary and epidemiological studies in collaboration with field-based collaborators. Dr. Brindley currently has funded research projects in the US (dealing with molecular genetics and transgenesis of schistosome parasites), and in north-east Thailand, dealing with liver fluke associated liver cancer, and southern China dealing with the genome of Schistosoma japonicum and the effects of the Three Gorges Dam on the spread of schistosomiasis and hookworm disease.

Brindley lab group, as at March 2009

Research Interests Top

• Development of molecular tools for introducing transgenes into the schistosome genome

• Gene discovery and exploration of genetic diversity in the Schistosoma japonicum and S. mansoni genomes (in collaboration with the NIH/NIAID funded Tropical Medicine Research Center in Shanghai, China, “Emerging Helminthiases in China”).

• Pathogenesis of liver fluke induced liver cancer (cholangiocarcinoma) in Thailand. (NIH/NIAID funded: Thailand-Tulane - International Collaboration for Infectious Diseases Research).

• Characterization of the phenomenon and biochemical pathways of proteolysis of ingested host hemoglobin in schistosomes and other blood-feeding helminth parasites.

• Molecular basis for host specificity in hematophagous parasites including hookworms, schistosomes, etc: exploration of the contribution of parasite hemoglobin-digesting enzymes to host range.

Selected Publications Top

Brindley PJ, Mitreva M, Ghedin E, Lustigman S. (2009) Helminth genomics: Implications for human health. PLoS Neglected Tropical Diseases 3(10): e538.

Smout, M.J., Laha, T., Mulvenna, J., Sripa, B., Suttiprapa, S., Jones, A., Brindley, P.J., Loukas, A. (2009) A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells. PLoS Pathogens 5(10):e1000611.

Mann, V.H., Morales, M.E., Rinaldi, G., Brindley, P.J. (2009) Culture for genetic manipulation of developmental stages of Schistosoma mansoni. Parasitology epub: doi:10.1017/S0031182009991211

Copeland, C.C., Marz, M., Rose, D., Hertel, J., Brindley, P.J., Bermudez-Santan, C., Kehr, S., Attoloni, S-O., Stadler, P.F. (2009) Homology-based annotation of non-coding RNAs in the genomes of Schistosoma mansoni and Schistosoma japonicum. BMC Genomics 10(1):464.

Sripa, B., Mairiang, E., Thinkhamrop, B., Laha, T., Kaewkes, S., Sithithaworn, P., Tessana, S., Loukas, A., Brindley, P.J., Bethony, J.M. (2009) Advanced periductal fibrosis from infection with the carcinogenic human liver fluke Opisthorchis viverrini correlates with elevated levels of IL-6 . Hepatology 50(4), 1273-81.

Schistosoma japonicum Genome Sequencing and Functional Analysis Consortium, Liu, F., Zhou, Y., Wang, ZQ., Lu, G., Zheng, H., Brindley, P.J., McManus, D.P., Blair, D., Zhang, QH., Zhong, Y., Wang, S., Han, ZG., Chen, Z. (2009) The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature 460, 345-352.

Rinaldi, G., Morales, M.E., Alrefaei, Y.N., Cancela, M., Castillo, E., Dalton, J.P., Tort, J.F., Brindley, P.J. (2009) RNA interference targeting leucine aminopeptidase blocks hatching of Schistosoma mansoni eggs. Molecular & Biochemical Parasitology 167, 118-126.

Han, ZG., Brindley, P.J. Wang, S., Chen, Z. (2009) Schistosome genomics: new perspectives on schistosome biology and host parasite interaction. Annual Review of Genomics and Human Genetics 10, 211-240.

Pinlaor, P., Kaepitoon, N., Laha, T., Sripa, B., Kaewkes, S., Morales, M.E., Mann, V.H., Parriott, S.K., Suttiprapa, S., Robinson, M.W., To, J., Dalton, J.P., Loukas, A., Brindley, P.J. (2009) Cathepsin F cysteine protease of Opisthorchis viverrini. PLoS Neglected Tropical Diseases 3(3): e398. PMC2654340

Gobert, G.N., Moertel, L., Brindley, P.J., McManus, D.P. (2009) Developmental gene expression profiles of the human pathogen Schistosoma japonicum.BMC Genomics 10:128.

Suttiprapa, S., Mulvenna, J., Huong, N.T., Pearson, M.S., Brindley, P.J., Laha, T., Sripa, B., Loukas, A. (2009) Ov- APR-1, an aspartic protease from the carcinogenic liver fluke, Opisthorchis viverrini: functional expression, immunolocalization and subsite specificity. International Journal of Biochemistry & Cell Biology 41, 1148-1156.

Dalton, J.P., Brindley, P.J., Donnelly, S., Robinson, M.W. (2009) The enigmatic asparaginyl endopeptidase of helminth parasites. Trends in Parasitology 25, 59-61.

Kines, K.J., Morales, M.E., Mann, V.H., Gobert, G.N., Brindley, P.J. (2008) Integration of reporter transgenes into Schistosoma mansoni chromosomes mediated by pseudotyped murine leukemia virus. The FASEB Journal 22, 2936-2948. PMC Journal - In Process

Hotez, P.J., Brindley, P.J., Bethony, J.M., Pearce, E.J., King, C.H., Jacobson, J. (2008) Helminth infections: the great neglected tropical diseases. Journal of Clinical Investigation 118, 1311-1321. PMC2440534

Hotez, P.J., Bethony, J.M., Oliveira, S.C., Brindley, P.J., Loukas, A. (2008) A multivalent anthelminthic vaccine to prevent hookworm and schistosomiasis. Expert Review of Vaccines 7, 745-752.

Rinaldi, G., Morales, M.E., Cancela, M., Castillo, E., Brindley, P.J., Tort, J.F. (2008) Development of functional genomics tools in trematodes: RNA interference and luciferase reporter gene activity in Fasciola hepatica. PLoS Neglected Tropical Diseases 2( 7): e260. PMC2440534

Yin, M.B., Mo, X., Hu, W., Wang, S-Y., Brindley, P.J., McManus, D.P., Davis, G.M., Zheng, F., Blair, D. (2008). Multiple near-identical genotypes of Schistosoma japonicum can occur in snails and have implications for population-genetic analyses. International Journal for Parasitology 38, 1681-1691. PMC Journal - In Process

Suttiprapa, S., Loukas, A., Laha, T., Pongkham, S., Kaewkes, S., Gaze, S., Brindley, P.J., Sripa, B. (2008) Characterization of the antioxidant enzyme, thioredoxin peroxidase, from the carcinogenic liver fluke, Opisthorchis viverrini. Molecular & Biochemical Parasitology 160, 116-122 .

Laha, T., Sripa, J., Sripa, B., Pearson, M., Tribolet, L., Keawkes, S., Sithithaworn, P., Brindley, P.J., Loukas, A. (2008) Asparaginyl endopeptidase from the carcinogenic liver fluke, Opisthorchis viverrini, and its potential for serodiagnosis. International Journal of Infectious Diseases (in press).

Kaewpitoon, N., Laha, T., Kaewkes, S., Yongvanit, P., Brindley, P.J., Loukas, A., Sripa, B. (2008) Characterization of cysteine proteases from the carcinogenic liver fluke, Opisthorchis viverrini. Parasitology Research 102, 757-764.

Morales, M.E., Rinaldi, G., Kines, K.J., Gobert, G.N., Tort, J.F., Brindley, P.J. (2008) RNA Interference targeting Schistosoma mansoni cathepsin D, the apical enzyme of the hemoglobin proteolysis cascade. Molecular and Biochemical Parasitology 157, 160-168. PMC Journal – In Process

Mann, V.H., Morales, M.E., Kines, K.J., Brindley, P.J. (2008) Transgenesis of schistosomes: approaches using mobile genetic elements. Parasitology 135, 141-153.

Fan, J., Yang, W., Brindley, P.J. (2008) Lysophospholipase from the human blood fluke, Schistosoma japonicum. International Journal of Infectious Diseases 12, 143-151.

Morales, M.E., Mann, V.H., Kines, K.J., Gobert, G.N., Fraser, M.J. Jr., Kalinna, B.H., Correnti, J.M., Pearce, E.J., Brindley, P.J. (2007) piggyBac transposon mediated transgenesis of the human blood fluke, Schistosoma mansoni. The FASEB Journal 21, 3479-3489. PMC Journal - In Process

Laha, T., Pinlaor, P., Mulvenna, J., Sripa, B., Sripa, M., Smout, M.J., Gasser, R.B., Brindley, P.J., Loukas, A. (2007) Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini. BMC Genomics 8:189. PMC1913519

Laha, T., Loukas, A., Wattanasatitarpa, S., Somprakhon, J., Kewgrai, N., Loukas, A., Sithithaworn, P., Kaewkes, S., Mitreva, M., Brindley, P.J. (2007) The bandit transposon, a mariner-like mobile genetic element from the genome of the hookworm, Ancylostoma caninum: inferred horizontal transmission between host and parasite. PLoS Neglected Tropical Diseases 1( 1): e35. PMC2041818

PLoS Medicine 4(7): e201. PMC1913093

Sripa, B., Kwaekes, S., Sithithaworn, P., Mairiang, E., Laha, T., Smout, M., Pairojkuli, C., Bhudhisawasdi, V., Tesana, S., Thinkamrop, B., Bethony, J.M., Loukas, A., Brindley, P.J. (2007) Liver fluke induces cholangiocarcinoma.

Copeland, C.S., Mann, V.H., Brindley, P.J. (2007) Both sense and antisense strands of the LTR of the Schistosoma mansoni Pao-like retrotransposon Sinbad drive luciferase expression. Molecular Genetics and Genomics 277, 161-170.

Brindley, P.J., Pearce, E.J. (2007) Genetic manipulation of schistosomes. Int J Parasitol 37,465-473.

Kalinna, B.H., Brindley, P.J. (2007) Manipulating the manipulators: advances in parasitic helminth transgenesis. Trends in Parasitology 23, 197-204.

Kines, K.J., Mann, V.H., Morales, M.E., Shelby, B.F., Kalinna, B.H., Gobert, G.N., Chirgwin, S.R.,

Brindley, P.J. (2006) Transduction of Schistosoma mansoni by vesicular stomatitis virus glycoprotein- pseudotyped Moloney murine leukemia retrovirus. Experimental Parasitology 112, 209-220 .

Liu, F., Lu, J., Hu, W., Wang, S-Y., Cui, S-J., Chi, M., Yan, Q., Wang, X-R., Song, H-D., Xu, X-N., Wang, J-J., Zhang, X-L., Zhang, X., Wang, Z-Q., Xue, C-L., Brindley, P.J., McManus, D.P., Feng, Z., Chen, Z., Han, Z-G. (2006) Comparative transcriptomic and proteomic analyses of the human blood fluke, Schistosoma japonicum.PLoS Pathogens 2 (4): e29. PMC1435792

Contact Information Top

Department of Microbiology, Immunology & Tropical Medicine
George Washington University Medical  Center
Ross Hall, Room 448,
2300 Eye Street, NW
Washington, DC 20037 USA
Fax: +1 202 994 2913
Phone: +1 202 994 3080

Email:
mtmvhm@gwumc.edu (Dr. Victoria Mann)
mtmpjb@gwumc.edu (Dr. Paul Brindley)