Photograph of Professor Karl Hoffmann.Professor Karl Hoffmann

Professor of Parasitology and Leader of the Animal & Microbial Sciences (AMS) Research Theme
PhD

Contact

Email: krh@aber.ac.uk
Office: 3.31, Edward Llwyd Building, Penglais
Phone: 01970 622237

Research

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.

Staff Links

Publications

2015

Reimers, N., Homann, A., Höschler, B., Langhans, K., Wilson, R.A., Pierrot, C., Khalife, J., Grevelding, C.G., Chalmers, I.W., Yazdanbakhsh, M., Hoffmann, K.F., Hokke, C.H., Haas, H., Schramm, G. 2015. Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7. PLoS Neglected Tropical Diseases 9 (3) e0003593 10.1371/journal.pntd.0003593

Smit, C.H., van Diepen, A., Nguyen, D.L., Wuhrer, M., Hoffmann, K.F., Deelder, A.M., Hokke, C.H. 2015. 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 Other

Chalmers, I.W., Fitzsimmons, C.M., Brown, M., Pierrot, C., Jones, F.M., Wawrzyniak, J.M., Fernandez-Fuentes, N., Tukahebwa, E.M., Dunne, D.W., Khalife, J., Hoffmann, K.F. 2015. 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.0003920

Nowacki, F.C., Swain, M.T., Klychnikov, O.I., Niazi, U., Ivens, A., Quintana, J.F., Hensbergen, P.J., Hokke, C.H., Buck, A.H., Hoffmann, K.F. 2015. Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni. Journal of Extracellular Vesicles 4 28665 10.3402/jev.v4.28665 Other

Hoffmann, K. 2015. 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.

Edwards, J., Brown, M., Peak, E., Bartholomew, B., Nash, R.J., Hoffmann, K.F. 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.0003604

2014

Hai, Y., Edwards, J., Van Zandt, M.C., Hoffmann, K.F., Christianson, D.W. 2014. Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis. Biochemistry 53 (28) pp. 4671-4684. 10.1021/bi5004519

Yoshino, T.P., Brown, M., Wu, X., Jackson, C.J., Ocadiz-Ruiz, R., Chalmers, I.W., Kolb, M., Hokke, C.H., Hoffmann, K.F. 2014. 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.2014.04.002

Hoffmann, K.F., Brindley, P.J., Berriman, M. 2014. Halting harmful helminths: Vaccines and new drugs are needed to combat parasitic worm infections. Science 346 (168) pp. 168-169. 10.1126/science.1261139

2013

Geyer, K.K., Chalmers, I.W., MacKintosh, N.D., Hirst, J.E., Geoghegan, R., Badets, M., Brophy, P.M., Brehm, K., Hoffmann, K.F. 2013. Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes. BMC Genomics 14 462 10.1186/1471-2164-14-462

Truscott, M., Evans, D.A., Gunn, M., Hoffmann, K.F. 2013. 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.00701-12

2012

Brehm, K., Carlton, J.M., Hoffmann, K.F. 2012. Editorial: Parasite genomics and post-genomic activities: 21st century resources for the parasite immunologist. Parasite Immunology 34 (2-3) pp. 47-49. 10.1111/j.1365-3024.2011.01346.x Other

Geyer, K.K., Hoffmann, K.F. 2012. Epigenetics: a key regulator of platyhelminth developmental biology? International Journal for Parasitology 42 (3) pp. 221-224. 10.1016/j.ijpara.2012.02.003

Chalmers, I.W., Hoffmann, K.F. 2012. 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/S0031182012000704

Fitzsimmons, C.M., Jones, F.M., Stearn, A., Chalmers, I.W., Hoffmann, K.F., Wawrzyniak, J., Wilson, S., Kabatereine, N.B., Dunne, D.W. 2012. 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.0001593

2011

Peak, E., Hoffmann, K. 2011. 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/S0001-37652011000200024

Geyer, K.K., Rodríguez-López, C.M., Hoffmann, K.F., Chalmers, I.W., Munshi, S.E., Truscott, M., Heald, J.K., Wilkinson, M.J., Hoffmann, K.F. 2011. Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni. Nature Communications 2 424 10.1038/ncomms1433 Cadair

2011. Dual fluorescence assay.

Swain, M.T., Larkin, D.M., Caffrey, C.R., Davies, S.J., Loukas, A., Skelly, P.J., Hoffmann, K.F. 2011. Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery. Trends in Parasitology 27 (12) pp. 555-564. 10.1016/j.pt.2011.09.003

2010

Peak, E., Chalmers, I.W., Hoffmann, K.F. 2010. 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 Other

2009

Fitzpatrick, J.M., Peak, E., Perally, S., Chalmers, I.W., Barrett, J., Yoshino, T.P., Ivens, A.C., Hoffmann, K.F. 2009. Anti-schistosomal intervention targets identified by lifecycle transcriptomic analyses. PLoS Neglected Tropical Diseases 3 (11) e543. 10.1371/journal.pntd.0000543 Cadair

Peak, E., Chalmers, I.W., Hoffmann, K.F. 2009. 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.

Fitzpatrick, J.M., Fuentes, J.M., Chalmers, I.W., Wynn, T.A., Modolell, M., Hoffmann, K.F., Hesse, M. 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 Cadair

Truscott, M., Hoffmann, K.F. 2009. 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.

Geyer, K., Rodrigues Lopez, C.M., Wilkinson, M.J., Hoffmann, K.F. 2009. The Schistosoma mansoni genome is methylated. The Schistosome Molecular Toolbox Workshop, University of California, , 16/09/2009 - 18/09/2009.

2008

Lockyer, A.E., Spinks, J., Kane, R.A., Hoffmann, K.F., Fitzpatrick, J.M., Rollinson, D., Noble, L.R., Jones, C.S. 2008. 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 Cadair

Chalmers, I.W., McArdle, A.J., Coulson, R.M.R., Wagner, M.A., Schmid, R., Hirai, H., Hoffmann, K.F. 2008. 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 Other

Fitzpatrick, J.M., Protasio, A.V., McArdle, A.J., Williams, G.A., Johnston, D.A., Hoffmann, K.F. 2008. 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 Other

2007

Hokke, C.H., Deelder, A.M., Hoffmann, K.F., Wuhrer, M. 2007. Glycomics-driven discoveries in schistosome research. Experimental Parasitology 117 (3) pp. 275-283. 10.1016/j.exppara.2007.06.003

Hokke, C.H., Fitzpatrick, J.M., Hoffmann, K.F. 2007. Integrating transcriptome, proteome and glycome analyses of Schistosoma biology. Trends in Parasitology 23 (4) pp. 165-174. 10.1016/j.pt.2007.02.007

Grevelding, C.G., Hoffmann, K.F. 2007. Schistosome genomics and beyond: News and views. Experimental Parasitology 117 (3) pp. 223-224. 10.1016/j.exppara.2007.09.001 Cadair

2006

Fitzpatrick, J.M., Hoffmann, K.F. 2006. Dioecious Schistosoma mansoni express divergent gene repertoires regulated by pairing. International Journal for Parasitology 36 (10-11) pp. 1081-1089. 10.1016/j.ijpara.2006.06.007

Reimert, C.M., Fitzsimmons, C.M., Joseph, S., Mwatha, J.K., Jones, F.M., Kimani, G., Hoffmann, K.F., Booth, M., Kabatereine, N.B., Dunne, D.W., Vennervald, B.J. 2006. 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.13.5.584-593.2006

Wynn, T.A., Aliberti, J., Hoffmann, K.F., Jankovic, D., Feng, C.G., Kullberg, M.C., Sher, A. 2006. Experimental Models for the Analysis of IL-10 Function. In F. Marincola (ed), Interleukin-10. Taylor & Francis Cadair Other

Wuhrer, M., Koeleman, C.A.M., Fitzpatrick, J.M., Hoffmann, K.F., Deelder, A.M., Hokke, C.H. 2006. Gender-specific expression of complex-type N-glycans in schistosomes. Glycobiology 16 (10) pp. 991-1006. 10.1093/glycob/cwl020

Vermeire, J.J., Taft, A.S., Hoffmann, K.F., Fitzpatrick, J.M., Yoshino, T.P. 2006. 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.2006.01.006

Fitzpatrick, J.M., Hirai, Y., Hirai, H., Hoffmann, K.F. 2006. Schistosome egg production is dependent upon the activities of two developmentally regulated tyrosinases. FASEB Journal 21 (3) pp. 823-835. 10.1096/fj.06-7314com Other Cadair

2005

Fitzpatrick, J.M., Johnston, D.A., Williams, G.W., Williams, D.J., Freeman, T.C., Dunne, D.W., Hoffmann, K.F. 2005. 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 Cadair

Fitzsimmons, C.M., Schramm, G., Jones, F.M., Chalmers, I.W., Hoffmann, K.F., Grevelding, C.G., Wuhrer, M., Hokke, C.H., Haas, H., Doenhoff, M.J., Dunne, D.W. 2005. 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.2005.08.003

Fitzpatrick, J.M., Hoffmann, K.F. 2005. The Application of DNA Microarrays in the Functional Genomic Study of Schistosome/Host Biology. Schistosomiasis: World Class Parasites Volume 10. Springer pp. 101-112. Cadair Other

2004

Fitzsimmons, C.M., Joseph, S., Jones, F.M., Reimert, C.M., Hoffmann, K.F., Kazibwe, F., Kimani, G., Mwatha, J.K., Ouma, J.H., Tukahebwa, E.M., Kariuki, H.C., Vennervald, B.J., Kabatereine, N.B., Dunne, D.W. 2004. 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.72.7.4023-4030.2004

Fitzpatrick, J.M., Johansen, M.V., Johnston, D.A., Dunne, D.W., Hoffmann, K.F. 2004. Gender-associated gene expression in two related strains of Schistosoma japonicum. Molecular and Biochemical Parasitology 136 (2) pp. 191-209. 10.1016/j.molbiopara.2004.03.014

Hoffmann, K.F., Fitzpatrick, J.M. 2004. Gene Expression Studies Using Self-Fabricated Parasite cDNA Microarrays. In S. Melville (ed), Parasite Genomics Protocols. 270th edn, Humana Press pp. 219-236. Cadair Other

Fitzsimmons, C.M., Stewart, T.J., Hoffmann, K.F., Grogan, J.L., Yazdanbakhsh, M., Dunne, D.W. 2004. 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.x

Wynn, T.A., Hesse, M., Sandler, N.G., Kaviratne, M., Hoffmann, K.F., Chiaramonte, M.G., Reiman, R., Cheever, A.W., Sypek, J.P., Mentink-Kane, M.M. 2004. 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.20102

2003

Hoffmann, K.F., Dunne, D.W. 2003. Characterization of the Schistosoma transcriptome opens up the world of helminth genomics. Genome Biology 5 203 10.1186/gb-2003-5-1-203

2002

Schopf, L.R., Hoffmann, K.F., Cheever, A.W., Urban, J.F., Wynn, T.A. 2002. IL-10 is critical for host resistance and survival during gastrointestinal helminth infection. Journal of Immunology 168 (5) pp. 2383-2392. Other

Hoffmann, K.F., Johnston, D.A., Dunne, D.W. 2002. Identification of Schistosoma mansoni gender-associated gene transcripts by cDNA microarray profiling. Genome Biology 3 (8) pp. RESEARCH0041. 10.1186/gb-2002-3-8-research0041

2001

Hoffmann, K.F., McCarty, T.C., Segal, D.H., Chiaramonte, M., Hesse, M., Davis, E.M., Cheever, A.W., Meltzer, P.S., Morse, H.C., Wynn, T.A. 2001. 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.01-0306fje

Park, M.K., Hoffmann, K.F., Cheever, A.W., Amichay, D., Wynn, T.A., Farber, J.M. 2001. 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.69.11.6755-6768.2001

2000

Hoffmann, K.F., Cheever, A.W., Wynn, T.A. 2000. 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. Other

Cheever, A.W., Hoffmann, K.F., Wynn, T.A. 2000. Immunopathology of schistosomiasis mansoni in mice and men. Immunology Today 21 (9) pp. 465-466. 10.1016/S0167-5699(00)01626-1

1999

Hoffmann, K.F., James, S.L., Cheever, A.W., Wynn, T.A. 1999. 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. Other

1998

Hoffmann, K.F., Caspar, P., Cheever, A.W., Wynn, T.A. 1998. 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.

1997

Hoffmann, K.F., Strand, M. 1997. 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.

1996

Hoffmann, K.F., Strand, M. 1996. 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.271.42.26117