Professor Karl Hoffmann
Professor of Parasitology and Leader of the Animal & Microbial Sciences (AMS) Research Theme
Office: 3.31, Edward Llwyd Building, Penglais
Phone: 01970 622237
Hoffmann Research Laboratory
Research in my laboratory revolves around trying to answer this question:
How can fundamental studies of developmental biology and gene regulation guide our search for next generation anthelmintic solutions?
Parasitic worms cause some of the most disfiguring, debilitating and chronic infectious diseases of human and animal populations across the globe. The reliance on limited drug classes to treat affected individuals and the lack of available vaccines to induce protective immunity suggests that current experimental approaches in identifying urgently needed anthelmintics have yet to deliver sustainable solutions.
Acknowledging this challenge and utilising both hypothesis-led and discovery driven research approaches, my laboratory is developing new strategies for controlling parasitic helminths of biomedical importance. Our specific area of expertise is Schistosoma mansoni, one of the three main trematode species responsible for the neglected tropical disease schistosomiasis. Currently, greater than 200 million people suffer from this chronic and debilitating disease, with 90% of all worldwide cases found in poverty-stricken areas of sub-Saharan Africa where up to 300, 000 individuals will die each year. Praziquantel is the current drug of choice used to treat schistosomiasis, but the need for repetitive treatment in endemic communities, concerns over the development of drug resistance and an unknown mechanism of action all have contributed to the active search for new chemotherapeutic agents or an effective prophylactic vaccine.
To identify next generation anthelmintics, we have chosen to look for solutions in the interrelated disciplines of helminth developmental biology, epigenetics and gene regulation. Current research activities include individual-gene and (epi) genome-wide investigations and are supported by experimental models of schistosome infection as well as objective analyses of helminth viability and phenotype. We envision that our integrated approach in the study of schistosome biology will enable tremendous strides to be made against an intractable human disease affecting some of the most disadvantaged populations of the developing world.
Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7. PLoS Neglected Tropical Diseases 9 (3) e0003593 10.1371/journal.pntd.00035932015.
Glycomic analysis of life stages of the human parasite Schistosoma mansoni reveals developmental expression profiles of functional and antigenic glycan motifs. Molecular and Cellular Proteomics 14 (7) pp. 1750-1769. 10.1074/mcp.M115.048280 Other2015.
Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment. PLoS Neglected Tropical Diseases 9 (7) pp. e0003920. 10.1371/journal.pntd.00039202015.
Sharing expertise/data/reagents. Accelerating R&D for Neglected Diseases through Global Collaborations: WIPO Re:Search Partnership Stories 2013-2015. 2ndth edn, BIO Ventures for Global Health, Seattle, USA pp. 23.2015.
The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica. PLoS Neglected Tropical Diseases 9 (3) e0003604 10.1371/journal.pntd.00036042015.
Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis. Biochemistry 53 (28) pp. 4671-4684. 10.1021/bi50045192014.
Excreted/secreted Schistosoma mansoni venom allergen-like 9 (SmVAL9) modulates host extracellular matrix remodelling gene expression. International Journal for Parasitology 44 (8) pp. 551-563. 10.1016/j.ijpara.2014.04.0022014.
Halting harmful helminths: Vaccines and new drugs are needed to combat parasitic worm infections. Science 346 (168) pp. 168-169. 10.1126/science.12611392014.
Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes. BMC Genomics 14 462 10.1186/1471-2164-14-4622013.
Schistosoma mansoni Hemozoin Modulates Alternative Activation of Macrophages via Specific Suppression of Retnla Expression and Secretion. Infection and Immunity 81 (1) pp. 133-142. 10.1128/IAI.00701-122013.
Epigenetics: a key regulator of platyhelminth developmental biology? International Journal for Parasitology 42 (3) pp. 221-224. 10.1016/j.ijpara.2012.02.0032012.
Platyhelminth venom allergen-like (VAL) proteins: revealing structural diversity, class specific features and biological associations across the phylum. Parasitology 139 (10) pp. 1231-1245. 10.1017/S00311820120007042012.
The Schistosoma mansoni tegumental-allergen-like (TAL) protein family: influence of developmental expression on human IgE responses. PLoS Neglected Tropical Diseases 6 (4) e1593 10.1371/journal.pntd.00015932012.
Cross-disciplinary approaches for measuring parasitic helminth viability and phenotype. Anais da Academia Brasileira de Ciencias Anais de Academia Brasileira de Ciencias 83 (2) pp. 649-662. 10.1590/S0001-376520110002000242011.
2011. Dual fluorescence assay.
Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery. Trends in Parasitology 27 (12) pp. 555-564. 10.1016/j.pt.2011.09.0032011.
Development and validation of a quantitative, high-throughput, fluorescent-based bioassay to detect Schistosoma viability. PLoS Neglected Tropical Diseases 4 (7) e759 10.1371/journal.pntd.0000759 Cadair Other2010.
Development and validation of a quantitative, high-throughput, fluorescent-based bioassay to detect Schistosoma viability. The Schistosome Molecular Toolbox Workshop, University of California, , 16/09/2009 - 18/09/2009.2009.
Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activity. International Journal for Parasitology 39 (3) pp. 267-279. 10.1016/j.ijpara.2008.06.015 Cadair2009.
Schistosoma mansoni haemozoin affects macrophage phenotype in a changing cytokine milieu. British Society for Parasitology, Spring Meeting, United Kingdom of Great Britain and Northern Ireland, 06/04/2009 - 08/04/2009.2009.
The Schistosoma mansoni genome is methylated. The Schistosome Molecular Toolbox Workshop, University of California, , 16/09/2009 - 18/09/2009.2009.
Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni. BMC Genomics 9 634 10.1186/1471-2164-9-634 Cadair2008.
Developmentally regulated expression, alternative splicing and distinct sub-groupings in members of the Schistosoma mansoni venom allergen-like (SmVAL) gene family. BMC Genomics 9 (89) 89 10.1186/1471-2164-9-89 Cadair Other2008.
Use of Genomic DNA as an Indirect Reference for Identifying Gender-Associated Transcripts in Morphologically Identical, but Chromosomally Distinct, Schistosoma mansoni Cercariae. PLoS Neglected Tropical Diseases 2 (10) e323 10.1371/journal.pntd.0000323 Cadair Other2008.
Glycomics-driven discoveries in schistosome research. Experimental Parasitology 117 (3) pp. 275-283. 10.1016/j.exppara.2007.06.0032007.
Integrating transcriptome, proteome and glycome analyses of Schistosoma biology. Trends in Parasitology 23 (4) pp. 165-174. 10.1016/j.pt.2007.02.0072007.
Dioecious Schistosoma mansoni express divergent gene repertoires regulated by pairing. International Journal for Parasitology 36 (10-11) pp. 1081-1089. 10.1016/j.ijpara.2006.06.0072006.
Eosinophil activity in Schistosoma mansoni infections in vivo and in vitro in relation to plasma cytokine profile pre- and posttreatment with praziquantel. Clinical and Vaccine Immunology 13 (5) pp. 584-593. 10.1128/CVI.13.5.584-593.20062006.
Gender-specific expression of complex-type N-glycans in schistosomes. Glycobiology 16 (10) pp. 991-1006. 10.1093/glycob/cwl0202006.
Schistosoma mansoni: DNA microarray gene expression profiling during the miracidium-to-mother sporocyst transformation. Molecular and Biochemical Parasitology 147 (1) pp. 39-47. 10.1016/j.molbiopara.2006.01.0062006.
An oligonucleotide microarray for transcriptome analysis of Schistosoma mansoni and its application/use to investigate gender-associated gene expression. Molecular and Biochemical Parasitology 141 (1) pp. 1-13. 10.1016/j.molbiopara.2005.01.007 Cadair2005.
Molecular characterization of omega-1: A hepatotoxic ribonuclease from Schistosoma mansoni eggs. Molecular and Biochemical Parasitology 144 (1) pp. 123-127. 10.1016/j.molbiopara.2005.08.0032005.
Chemotherapy for schistosomiasis in Ugandan fishermen: Treatment can cause a rapid increase in interleukin-5 levels in plasma but decreased levels of eosinophilia and worm-specific immunoglobulin E. Infection and Immunity 72 (7) pp. 4023-4030. 10.1128/IAI.72.7.4023-4030.20042004.
Gender-associated gene expression in two related strains of Schistosoma japonicum. Molecular and Biochemical Parasitology 136 (2) pp. 191-209. 10.1016/j.molbiopara.2004.03.0142004.
Human IgE response to the Schistosoma haematobium 22.6 kDa antigen. Parasite Immunology 26 (8-9) pp. 371-376. 10.1111/j.0141-9838.2004.00721.x2004.
P-selectin suppresses hepatic inflammation and fibrosis in mice by regulating interferon gamma and the IL-13 decoy receptor. Hepatology 39 (3) pp. 676-687. 10.1002/hep.201022004.
Characterization of the Schistosoma transcriptome opens up the world of helminth genomics. Genome Biology 5 203 10.1186/gb-2003-5-1-2032003.
IL-10 is critical for host resistance and survival during gastrointestinal helminth infection. Journal of Immunology 168 (5) pp. 2383-2392. Other2002.
Identification of Schistosoma mansoni gender-associated gene transcripts by cDNA microarray profiling. Genome Biology 3 (8) pp. RESEARCH0041. 10.1186/gb-2002-3-8-research00412002.
Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type-1 and type-2 cytokine-mediated inflammatory reactions. FASEB Journal 15 (13) pp. 2545-25477. 10.1096/fj.01-0306fje2001.
Patterns of chemokine expression in models of Schistosoma mansoni inflammation and infection reveal relationships between type 1 and type 2 responses and chemokines in vivo. Infection and Immunity 69 (11) pp. 6755-6768. 10.1128/IAI.69.11.6755-6768.20012001.
IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. Journal of Immunology 164 (12) pp. 6406-6416. Other2000.
Immunopathology of schistosomiasis mansoni in mice and men. Immunology Today 21 (9) pp. 465-466. 10.1016/S0167-5699(00)01626-12000.
Studies with double cytokine-deficient mice reveal that highly polarized Th1- and Th2-type cytokine and antibody responses contribute equally to vaccine-induced immunity to Schistosoma mansoni. Journal of Immunology 163 (2) pp. 927-938. Other1999.
IFN-gamma, IL-12, and TNF-alpha are required to maintain reduced liver pathology in mice vaccinated with Schistosoma mansoni eggs and IL-12. Journal of Immunology 161 (8) pp. 4201-4210.1998.
Molecular characterization of a 20.8-kDa Schistosoma mansoni antigen. Sequence similarity to tegumental associated antigens and dynein light chains. Journal of Biological Chemistry 272 (23) pp. 14509-14515.1997.
Molecular identification of a Schistosoma mansoni tegumental protein with similarity to cytoplasmic dynein light chains. Journal of Biological Chemistry 271 (42) pp. 26117-26123. 10.1074/jbc.271.42.261171996.