Prof Karl Hoffmann


Prof Karl Hoffmann


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Flatworm Functional Genomics Initiative (FUGI):



My research revolves around trying to answer this question: How can fundamental studies of developmental biology & gene regulation guide our search for next generation anthelmintic solutions?

Parasitic worms cause some of the most disfiguring, debilitating & chronic infectious diseases of human & animal populations across the globe. Reliance on limited drug classes to treat affected individuals & 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.

Utilising both hypothesis-led & discovery driven research approaches my laboratory is developing new strategies for controlling parasitic helminths of biomedical importance. Our area of expertise is Schistosoma mansoni, one of the three main trematode species responsible for the neglected tropical disease Schistosomiasis. More than 200 million people suffer from this chronic & debilitating disease, with 90% of all worldwide cases found in poverty-stricken areas of sub-Saharan Africa where up to 300,000 individuals die each year. Praziquantel is currently used to treat schistosomiasis, but the need for repetitive treatment in endemic communities, concerns over the development of resistance & an unknown mechanism of action all have contributed to the active search for new chemotherapeutic agents or a prophylactic vaccine.

To identify next generation anthelmintics we look for solutions in the interrelated disciplines of helminth developmental biology, epigenetics & gene regulation. Our research includes individual-gene & (epi) genome-wide investigations, supported by experimental models of schistosome infection & objective analyses of helminth viability & phenotype. We envision that our integrated approach will


Design, synthesis and anthelmintic activity of 7-keto-sempervirol analoguesCrusco, A., Bordoni, C., Chakroborty, A., Whatley, K. C. L., Whiteland, H., Westwell, A. D. & Hoffmann, K. 2018 In : European Journal of Medicinal Chemistry.152, p. 87-100
The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulation transcription, translation and stem cell activitiesGeyer, K., Munshi, S. E., Vickers, M., Squance, M., Wilkinson, T., Berrar, D., Chaparro, C., Swain, M. & Hoffmann, K. 2018 In : International Journal for Parasitology: Drugs and Drug Resistance.8, 2, p. 213-22210 p.
Rethinking Schistosomiasis Vaccine Development: Synthetic VesiclesEgesa, M., Hoffmann, K., Hokke, C. H., Yazdanbakhsh, M. & Cose, S. 2017 In : Trends in Parasitology.1671, 4 p.
Neoclerodane Diterpenoids from Reehal Fatima, Teucrium yemenseNur-e-Alam, M., Yousaf, M., Ahmed, S., Al-Sheddi, E. S., Shah, I., Fazakerley, D., Bari, A., Ghabbour, H. A., Threadgill, M. D., Whatley, K., Hoffmann, K. & Al-Rehaily, A. J. 2017 In : Journal of Natural Products.
Whole genome analysis of a schistosomiasis-transmitting freshwater snailAdema, C. M., Hillier, L. W., Jones, C. S., Loker, E. S., Knight, M., Minx, P., Oliveira, G., Raghavan, N., Shedlock, A., do Amaral, L. R., Arican-Goktas, H. D., Assis, J. G., Baba, E. H., Baron, O. L., Bayne, C. J., Bickham-Wright, U., Biggar, K. K., Blouin, M., Bonning, B. C., Botka, C., Bridger, J. M., Buckley, K. M., Buddenborg, S. K., Lima Caldeira, R., Carleton, J., Carvalho, O. S., Castillo, M. G., Chalmers, I. W., Christensens, M., Clifton, S., Cosseau, C., Coustau, C., Cripps, R. M., Cuesta-Astroz, Y., Cummins, S. F., Di Stephano, L., Dinguirard, N., Duval, D., Emrich, S., Feschotte, C., Feyereisen, R., Fitzgerald, P., Fronick, C., Fulton, L., Galinier, R., Gava, S. G., Geusz, M., Geyer, K. K., Giraldo-Calderón, G. I., de Souza Gomes, M., Gordy, M. A., Gourbal, B., Grunau, C., Hanington, P. C., Hoffmann, K. F., Hughes, D., Humphries, J., Jackson, D. J., Jannotti-Passos, L. K., De Jesus Jeremias, W., Jobling, S., Kamel, B., Kapusta, A., Kaur, S., Koene, J. M., Kohn, A. B., Lawson, D., Lawton, S. P., Liang, D., Limpanont, Y., Liu, S., Lockyer, A. E., Lovato, T. L., Ludolf, F., Magrini, V., Mcmanus, D. P., Medina, M., Misra, M., Mitta, G., Mkoji, G. M., Montague, M. J., Montelongo, C., Moroz, L. L., Munoz-Torres, M. C., Niazi, U., Noble, L. R., Oliveira, F. S., Pais, F. S., Papenfuss, A. T., Peace, R., Pena, J. J., Pila, E. A., Quelais, T., Raney, B. J., Rast, J. P., Rollinson, D., Rosse, I. C., Rotgans, B., Routledge, E. J., Ryan, K. M., Scholte, L. L. S., Storey, K. B., Swain, M., Tennessen, J. A., Tomlinson, C., Trujillo, D. L., Volpi, E. V., Walker, A. J., Wang, T., Wannaporn, I., Warren, W. C., Wu, X-J., Yoshino, T. P., Yusuf, M., Zhang, S-M., Zhao, M. & Wilson, R. K. 2017 In : Nature Communications.8, p. 15451 15451 (2017)
The Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoniGeyer, K., Niazi, U., Duval, D., Cosseau, C., Tomlinson, C., Chalmers, I., Swain, M., Cutress, D., Bickham-Wright, U., Munshi, S. E., Grunau, C., Yoshino, T. P. & Hoffmann, K. 2017 In : PLoS Neglected Tropical Diseases.11, 5, e0005246
(Epi)genetic Inheritance in Schistosoma mansoni: A Systems ApproachCosseau, C., Wolkenhauer, O., Padalino, G., Geyer, K., Hoffmann, K. & Grunau, C. 2017 In : Trends in Parasitology.33, 4, p. 285-2945 p.
DISMISS: MeDIP-seq: High-throughput sequencingNiazi, U., Geyer, K., Vickers, M., Hoffmann, K. & Swain, M. 2016
DISMISS: detection of stranded methylation in MeDIP-Seq dataNiazi, U., Geyer, K. K., Vickers, M. J., Hoffmann, K. & Swain, M. 2016 In : BMC Bioinformatics.17, 295
Sharing expertise/data/reagentsHoffmann, K. 2015 Accelerating R&D for Neglected Diseases through Global Collaborations: WIPO Re:Search Partnership Stories 2013-2015.2nd ed. Seattle, USA: BIO Ventures for Global Health, p. 23
Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoniNowacki, 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 In : Journal of Extracellular Vesicles.4, 28665
Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel TreatmentChalmers, 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 In : PLoS Neglected Tropical Diseases.9, 7, p. e0003920
Glycomic analysis of life stages of the human parasite Schistosoma mansoni reveals developmental expression profiles of functional and antigenic glycan motifsSmit, C. H., van Diepen, A., Nguyen, D. L., Wuhrer, M., Hoffmann, K. F., Deelder, A. M. & Hokke, C. H. 2015 In : Molecular and Cellular Proteomics.14, 7, p. 1750-1769
Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7Reimers, 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 In : PLoS Neglected Tropical Diseases.9, 3, e0003593
The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepaticaEdwards, J., Brown, M., Peak, E., Bartholomew, B., Nash, R. J. & Hoffmann, K. F. 2015 In : PLoS Neglected Tropical Diseases.9, 3, e0003604
Halting harmful helminths: Vaccines and new drugs are needed to combat parasitic worm infectionsHoffmann, K. F., Brindley, P. J. & Berriman, M. 2014 In : Science.346, 168, p. 168-1692 p.
Excreted/secreted Schistosoma mansoni venom allergen-like 9 (SmVAL9) modulates host extracellular matrix remodelling gene expressionYoshino, T. P., Brown, M., Wu, X-J., Jackson, C. J., Ocadiz-Ruiz, R., Chalmers, I. W., Kolb, M., Hokke, C. H. & Hoffmann, K. F. 2014 In : International Journal for Parasitology.44, 8, p. 551-56313 p.
Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of SchistosomiasisHai, Y., Edwards, J., Van Zandt, M. C., Hoffmann, K. F. & Christianson, D. W. 2014 In : Biochemistry.53, 28, p. 4671-4684
Cytosine methylation is a conserved epigenetic feature found throughout the phylum PlatyhelminthesGeyer, K. K., Chalmers, I. W., MacKintosh, N. D., Hirst, J. E., Geoghegan, R., Badets, M., Brophy, P. M., Brehm, K. & Hoffmann, K. F. 2013 In : BMC Genomics.14, 462
Schistosoma mansoni Hemozoin Modulates Alternative Activation of Macrophages via Specific Suppression of Retnla Expression and SecretionTruscott, M., Evans, D. A., Gunn, M. & Hoffmann, K. F. 2013 In : Infection and Immunity.81, 1, p. 133-14210 p.
Platyhelminth venom allergen-like (VAL) proteins: revealing structural diversity, class specific features and biological associations across the phylumChalmers, I. W. & Hoffmann, K. F. 2012 In : Parasitology.139, 10, p. 1231-124515 p.
The Schistosoma mansoni tegumental-allergen-like (TAL) protein family: influence of developmental expression on human IgE responsesFitzsimmons, C. M., Jones, F. M., Stearn, A., Chalmers, I. W., Hoffmann, K. F., Wawrzyniak, J., Wilson, S., Kabatereine, N. B. & Dunne, D. W. 2012 In : PLoS Neglected Tropical Diseases.6, 4, e1593
Epigenetics: a key regulator of platyhelminth developmental biology?Geyer, K. K. & Hoffmann, K. F. 2012 In : International Journal for Parasitology.42, 3, p. 221-2244 p.
Editorial: Parasite genomics and post-genomic activities: 21st century resources for the parasite immunologistBrehm, K., Carlton, J. M. & Hoffmann, K. F. 2012 In : Parasite Immunology.34, 2-3, p. 47-493 p.
Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discoverySwain, M. T., Larkin, D. M., Caffrey, C. R., Davies, S. J., Loukas, A., Skelly, P. J. & Hoffmann, K. F. 2011 In : Trends in Parasitology.27, 12, p. 555-56410 p.
Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoniGeyer, 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 In : Nature Communications.2, 424
Cross-disciplinary approaches for measuring parasitic helminth viability and phenotypePeak, E. & Hoffmann, K. 2011 In : Anais da Academia Brasileira de Ciências.83, 2, p. 649-66214 p.
Dual fluorescence assay.Peak, E. & Hoffmann, K. F. 2011
Development and Validation of a Quantitative, High-Throughput, Fluorescent-Based Bioassay to Detect Schistosoma ViabilityPeak, E., Chalmers, I. W. & Hoffmann, K. F. 2010 In : PLoS Neglected Tropical Diseases.4, 7, e759
Anti-schistosomal intervention targets identified by lifecycle transcriptomic analysesFitzpatrick, J. M., Peak, E., Perally, S., Chalmers, I. W., Barrett, J., Yoshino, T. P., Ivens, A. C. & Hoffmann, K. F. 2009 In : PLoS Neglected Tropical Diseases.3, 11, e543.
Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activityFitzpatrick, J. M., Fuentes, J. M., Chalmers, I. W., Wynn, T. A., Modolell, M., Hoffmann, K. F. & Hesse, M. 2009 In : International Journal for Parasitology.39, 3, p. 267-27913 p.
The Schistosoma mansoni genome is methylatedGeyer, K., Rodrigues Lopez, C. M., Wilkinson, M. J. & Hoffmann, K. F. 2009
Development and validation of a quantitative, high-throughput, fluorescent-based bioassay to detect Schistosoma viabilityPeak, E., Chalmers, I. W. & Hoffmann, K. F. 2009
Schistosoma mansoni haemozoin affects macrophage phenotype in a changing cytokine milieuTruscott, M. & Hoffmann, K. F. 2009
Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoniLockyer, A. E., Spinks, J., Kane, R. A., Hoffmann, K. F., Fitzpatrick, J. M., Rollinson, D., Noble, L. R. & Jones, C. S. 2008 In : BMC Genomics.9, 634
Use of Genomic DNA as an Indirect Reference for Identifying Gender-Associated Transcripts in Morphologically Identical, but Chromosomally Distinct, Schistosoma mansoni CercariaeFitzpatrick, J. M., Protasio, A. V., McArdle, A. J., Williams, G. A., Johnston, D. A. & Hoffmann, K. F. 2008 In : PLoS Neglected Tropical Diseases.2, 10, e323
Developmentally regulated expression, alternative splicing and distinct sub-groupings in members of the Schistosoma mansoni venom allergen-like (SmVAL) gene familyChalmers, I. W., McArdle, A. J., Coulson, R. M. R., Wagner, M. A., Schmid, R., Hirai, H. & Hoffmann, K. F. 2008 In : BMC Genomics.9, 89
Schistosome genomics and beyond: News and viewsGrevelding, C. G. & Hoffmann, K. F. 2007 In : Experimental Parasitology.117, 3, p. 223-2242 p.
Glycomics-driven discoveries in schistosome researchHokke, C. H., Deelder, A. M., Hoffmann, K. F. & Wuhrer, M. 2007 In : Experimental Parasitology.117, 3, p. 275-2839 p.
Integrating transcriptome, proteome and glycome analyses of Schistosoma biologyHokke, C. H., Fitzpatrick, J. M. & Hoffmann, K. F. 2007 In : Trends in Parasitology.23, 4, p. 165-17410 p.
Schistosome egg production is dependent upon the activities of two developmentally regulated tyrosinasesFitzpatrick, J. M., Hirai, Y., Hirai, H. & Hoffmann, K. F. 2006 In : FASEB Journal.21, 3, p. 823-83513 p.
Gender-specific expression of complex-type N-glycans in schistosomesWuhrer, M., Koeleman, C. A. M., Fitzpatrick, J. M., Hoffmann, K. F., Deelder, A. M. & Hokke, C. H. 2006 In : Glycobiology.16, 10, p. 991-100616 p.
Dioecious Schistosoma mansoni express divergent gene repertoires regulated by pairingFitzpatrick, J. M. & Hoffmann, K. F. 2006 In : International Journal for Parasitology.36, 10-11, p. 1081-10899 p.
Eosinophil activity in Schistosoma mansoni infections in vivo and in vitro in relation to plasma cytokine profile pre- and posttreatment with praziquantelReimert, 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 In : Clinical and Vaccine Immunology.13, 5, p. 584-59310 p.
Schistosoma mansoni: DNA microarray gene expression profiling during the miracidium-to-mother sporocyst transformationVermeire, J. J., Taft, A. S., Hoffmann, K. F., Fitzpatrick, J. M. & Yoshino, T. P. 2006 In : Molecular and Biochemical Parasitology.147, 1, p. 39-479 p.
Experimental Models for the Analysis of IL-10 FunctionWynn, T. A., Aliberti, J., Hoffmann, K. F., Jankovic, D., Feng, C. G., Kullberg, M. C. & Sher, A. 2006 Interleukin-10. Marincola, F. M. (ed.). Taylor & Francis
Molecular characterization of omega-1: A hepatotoxic ribonuclease from Schistosoma mansoni eggsFitzsimmons, 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 In : Molecular and Biochemical Parasitology.144, 1, p. 123-1275 p.
An oligonucleotide microarray for transcriptome analysis of Schistosoma mansoni and its application/use to investigate gender-associated gene expressionFitzpatrick, J. M., Johnston, D. A., Williams, G. W., Williams, D. J., Freeman, T. C., Dunne, D. W. & Hoffmann, K. F. 2005 In : Molecular and Biochemical Parasitology.141, 1, p. 1-1313 p.
The Application of DNA Microarrays in the Functional Genomic Study of Schistosome/Host BiologyFitzpatrick, J. M. & Hoffmann, K. F. 2005 Schistosomiasis: World Class Parasites Volume 10.Springer Nature, p. 101-11212 p.
Human IgE response to the Schistosoma haematobium 22.6 kDa antigenFitzsimmons, C. M., Stewart, T. J., Hoffmann, K. F., Grogan, J. L., Yazdanbakhsh, M. & Dunne, D. W. 2004 In : Parasite Immunology.26, 8-9, p. 371-3766 p.
Gender-associated gene expression in two related strains of Schistosoma japonicumFitzpatrick, J. M., Johansen, M. V., Johnston, D. A., Dunne, D. W. & Hoffmann, K. F. 2004 In : Molecular and Biochemical Parasitology.136, 2, p. 191-20919 p.
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 EFitzsimmons, 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 In : Infection and Immunity.72, 7, p. 4023-40308 p.
Gene Expression Studies Using Self-Fabricated Parasite cDNA MicroarraysHoffmann, K. F. & Fitzpatrick, J. M. 2004 Parasite Genomics Protocols. Melville, S. E. (ed.). 270 ed.Springer Nature, p. 219-23618 p.
P-selectin suppresses hepatic inflammation and fibrosis in mice by regulating interferon gamma and the IL-13 decoy receptorWynn, 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 In : Hepatology.39, 3, p. 676-68712 p.
Characterization of the Schistosoma transcriptome opens up the world of helminth genomicsHoffmann, K. F. & Dunne, D. W. 2003 In : Genome Biology.5, 203
Identification of Schistosoma mansoni gender-associated gene transcripts by cDNA microarray profilingHoffmann, K. F., Johnston, D. A. & Dunne, D. W. 2002 In : Genome Biology.3, 8, p. RESEARCH0041
IL-10 is critical for host resistance and survival during gastrointestinal helminth infectionSchopf, L. R., Hoffmann, K. F., Cheever, A. W., Urban, J. F. & Wynn, T. A. 2002 In : Journal of Immunology.168, 5, p. 2383-239210 p.
Patterns of chemokine expression in models of Schistosoma mansoni inflammation and infection reveal relationships between type 1 and type 2 responses and chemokines in vivoPark, M. K., Hoffmann, K. F., Cheever, A. W., Amichay, D., Wynn, T. A. & Farber, J. M. 2001 In : Infection and Immunity.69, 11, p. 6755-676814 p.
Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type-1 and type-2 cytokine-mediated inflammatory reactionsHoffmann, 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 In : FASEB Journal.15, 13, p. 2545-254773 p.
Immunopathology of schistosomiasis mansoni in mice and menCheever, A. W., Hoffmann, K. F. & Wynn, T. A. 2000 In : Immunology Today.21, 9, p. 465-4662 p.
IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasisHoffmann, K. F., Cheever, A. W. & Wynn, T. A. 2000 In : Journal of Immunology.164, 12, p. 6406-641611 p.
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 mansoniHoffmann, K. F., James, S. L., Cheever, A. W. & Wynn, T. A. 1999 In : Journal of Immunology.163, 2, p. 927-93812 p.
IFN-gamma, IL-12, and TNF-alpha are required to maintain reduced liver pathology in mice vaccinated with Schistosoma mansoni eggs and IL-12Hoffmann, K. F., Caspar, P., Cheever, A. W. & Wynn, T. A. 1998 In : Journal of Immunology.161, 8, p. 4201-421010 p.
Molecular characterization of a 20.8-kDa Schistosoma mansoni antigen. Sequence similarity to tegumental associated antigens and dynein light chainsHoffmann, K. F. & Strand, M. 1997 In : Journal of Biological Chemistry.272, 23, p. 14509-145157 p.
Molecular identification of a Schistosoma mansoni tegumental protein with similarity to cytoplasmic dynein light chainsHoffmann, K. F. & Strand, M. 1996 In : Journal of Biological Chemistry.271, 42, p. 26117-261237 p.