Prof Karl Hoffmann PhD
- Email: email@example.com
- 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 16712017.
Neoclerodane Diterpenoids from Reehal Fatima, Teucrium yemense. Journal of Natural Products Cadair2017.
Whole genome analysis of a schistosomiasis-transmitting freshwater snail. Nature Communications 8 15451 (2017) pp. 15451. Cadair2017.
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 Cadair2017.
(Epi)genetic Inheritance in Schistosoma mansoni: A Systems Approach. Trends in Parasitology 33 (4) pp. 285-294. Cadair2016.
DISMISS: MeDIP-seq: High-throughput sequencing.2016.
DISMISS: detection of stranded methylation in MeDIP-Seq data. BMC Bioinformatics 17 295 Cadair2016.
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.
Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni. Journal of Extracellular Vesicles 4 28665 Cadair2015.
Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment. PLoS Neglected Tropical Diseases 9 (7) pp. e0003920. 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. Cadair2015.
Drug-Induced Exposure of Schistosoma mansoni Antigens SmCD59a and SmKK7. PLoS Neglected Tropical Diseases 9 (3) e0003593 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 Cadair2015.
Halting harmful helminths: Vaccines and new drugs are needed to combat parasitic worm infections. Science 346 (168) pp. 168-169. Cadair2014.
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. Cadair2014.
Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis. Biochemistry 53 (28) pp. 4671-4684. Cadair2014.
Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes. BMC Genomics 14 462 Cadair2013.
Schistosoma mansoni Hemozoin Modulates Alternative Activation of Macrophages via Specific Suppression of Retnla Expression and Secretion. Infection and Immunity 81 (1) pp. 133-142. 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. 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 Cadair2012.
Epigenetics: a key regulator of platyhelminth developmental biology? International Journal for Parasitology 42 (3) pp. 221-224. Cadair2012.
Editorial: Parasite genomics and post-genomic activities: 21st century resources for the parasite immunologist. Parasite Immunology 34 (2-3) pp. 47-49. Cadair2012.
Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery. Trends in Parasitology 27 (12) pp. 555-564. Cadair2011.
Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni. Nature Communications 2 4242011.
Cross-disciplinary approaches for measuring parasitic helminth viability and phenotype. Anais da Academia Brasileira de Ciências 83 (2) pp. 649-662. Cadair2011.
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 Cadair2010.
Anti-schistosomal intervention targets identified by lifecycle transcriptomic analyses. PLoS Neglected Tropical Diseases 3 (11) e543.2009.
Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activity. International Journal for Parasitology 39 (3) pp. 267-279.2009.
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 6342008.
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) e3232008.
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) 892008.
Schistosome genomics and beyond: News and views. Experimental Parasitology 117 (3) pp. 223-224.2007.
Glycomics-driven discoveries in schistosome research. Experimental Parasitology 117 (3) pp. 275-283. Cadair2007.
Integrating transcriptome, proteome and glycome analyses of Schistosoma biology. Trends in Parasitology 23 (4) pp. 165-174. Cadair2007.
Dioecious Schistosoma mansoni express divergent gene repertoires regulated by pairing. International Journal for Parasitology 36 (10-11) pp. 1081-1089. Cadair2006.
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. Cadair2006.
Schistosoma mansoni: DNA microarray gene expression profiling during the miracidium-to-mother sporocyst transformation. Molecular and Biochemical Parasitology 147 (1) pp. 39-47. Cadair2006.
Experimental Models for the Analysis of IL-10 Function. In (ed) Interleukin-10. Taylor & Francis2006.
Schistosome egg production is dependent upon the activities of two developmentally regulated tyrosinases. FASEB Journal 21 (3) pp. 823-835.2006.
Gender-specific expression of complex-type N-glycans in schistosomes. Glycobiology 16 (10) pp. 991-1006. Cadair2006.
Molecular characterization of omega-1: A hepatotoxic ribonuclease from Schistosoma mansoni eggs. Molecular and Biochemical Parasitology 144 (1) pp. 123-127. Cadair2005.
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. 1-13.2005.
The Application of DNA Microarrays in the Functional Genomic Study of Schistosome/Host Biology. Schistosomiasis: World Class Parasites Volume 10. Springer Nature pp. 101-112.2005.
Human IgE response to the Schistosoma haematobium 22.6 kDa antigen. Parasite Immunology 26 (8-9) pp. 371-376. Cadair2004.
Gender-associated gene expression in two related strains of Schistosoma japonicum. Molecular and Biochemical Parasitology 136 (2) pp. 191-209. Cadair2004.
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. Cadair2004.
Gene Expression Studies Using Self-Fabricated Parasite cDNA Microarrays. In (ed) Parasite Genomics Protocols. 270th edn, Springer Nature pp. 219-236.2004.
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. Cadair2004.
Characterization of the Schistosoma transcriptome opens up the world of helminth genomics. Genome Biology 5 203 Cadair2003.
Identification of Schistosoma mansoni gender-associated gene transcripts by cDNA microarray profiling. Genome Biology 3 (8) pp. RESEARCH0041. Cadair2002.
IL-10 is critical for host resistance and survival during gastrointestinal helminth infection. Journal of Immunology 168 (5) pp. 2383-2392. Cadair2002.
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. 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. Cadair2001.
Immunopathology of schistosomiasis mansoni in mice and men. Immunology Today 21 (9) pp. 465-466. Cadair2000.
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. 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. 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.
Molecular identification of a Schistosoma mansoni tegumental protein with similarity to cytoplasmic dynein light chains. Journal of Biological Chemistry 271 (42) pp. 26117-26123. Cadair1996.