Prof Karl Hoffmann PhD
- Email: firstname.lastname@example.org
- Office: 3.31, Edward Llwyd Building
- Phone: +44 (0) 1970 622237
- Personal Website: https://www.aber.ac.uk/en/ibers/research/research-groups/parasitology_epidemiology_group/hoffmann_research_lab/
- Twitter: https://twitter.com/ProfHoff1
Flatworm Functional Genomics Initiative (FUGI): www.sanger.ac.uk/science/collaboration/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 enable progress to be made against an intractable disease affecting some of the most disadvantaged populations of the developing world.
Rethinking Schistosomiasis Vaccine Development: Synthetic Vesicles. Trends in Parasitology 1671 10.1016/j.pt.2017.07.0072017.
The Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoni. PLoS Neglected Tropical Diseases 11 (5) e0005246 10.1371/journal.pntd.0005246 Cadair2017.
DISMISS: MeDIP-seq: High-throughput sequencing. Other2016.
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. Cadair2015.
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 Cadair2015.
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 Cadair2015.
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 Cadair2015.
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 Cadair2014.
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 Cadair2013.
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 Cadair2012.
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 Cadair2012.
Dual fluorescence assay. Cadair2011.
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 Cadair2010.
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.
The Schistosoma mansoni genome is methylated. The Schistosome Molecular Toolbox Workshop. Cadair2009.
Development and validation of a quantitative, high-throughput, fluorescent-based bioassay to detect Schistosoma viability. The Schistosome Molecular Toolbox Workshop. Cadair2009.
Schistosoma mansoni haemozoin affects macrophage phenotype in a changing cytokine milieu. British Society for Parasitology. Cadair2009.
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.
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.
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.
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 Cadair2006.
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 Cadair2006.
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.
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 Cadair2004.
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 Cadair2001.
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 Cadair2001.
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 Cadair2000.
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 Cadair1999.
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. Cadair1998.
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. Cadair1997.