Prof Karl Hoffmann

PhD

Additional Information

PROJECT WEBPAGES:

Flatworm Functional Genomics Initiative (FUGI): www.sanger.ac.uk/science/collaboration/flatworm-functional-genomics-initiative-fugi

Teaching

Research

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.

Publications

Crusco, A, Whiteland, H, Baptista, R, Forde-Thomas, JE, Beckmann, M, Mur, LAJ, Nash, RJ, Westwell, AD & Hoffmann, KF 2019, 'Antischistosomal Properties of Sclareol and Its Heck-Coupled Derivatives: Design, Synthesis, Biological Evaluation and Untargeted Metabolomics' ACS Infectious Diseases. https://doi.org/10.1021/acsinfecdis.9b00034
Wannaporn, I, Mann, V, Karinshak, S, Coghlan, A, Rinaldi, G, Sankaranarayanan, G, Chaidee, A, Tanno, T, Kumkhaek, C, Prangtaworn, P, Mentink-Kane, MM, Cochran, CJ, Driguez, P, Holroyd, N, Tracey, A, Rodpai, R, Everts, B, Hokke, CH, Hoffmann, K, Berriman, M & Brindley, PJ 2019, 'Programmed genome editing of the omega-1 ribonuclease of the blood fluke, Schistosoma mansoni' eLife, vol. 8, e41337. https://doi.org/10.7554/eLife.41337
Farias, LP, Chalmers, IW, Perally, S, Rofatto, HK, Jackson, CJ, Brown, M, Khouri, MI, Barbosa, MMF, Hensbergen, PJ, Hokke, CH, Leite, LCC & Hoffmann, KF 2019, 'Schistosoma mansoni venom allergen-like proteins: phylogenetic relationships, stage-specific transcription and tissue localization as predictors of immunological cross-reactivity' International Journal for Parasitology. https://doi.org/10.1016/j.ijpara.2019.03.003
Crusco, A, Alves Baptista, R, Bhowmick, S, Beckmann, M, Mur, L, Westwell, AD & Hoffmann, K 2019, 'The anti-mycobacterial activity of a diterpenoid-like molecule operates through nitrogen and amino acid starvation' Frontiers in Microbiology, vol. 10, 01444. https://doi.org/10.3389/fmicb.2019.01444
Whiteland, H, Chakroborty, A, Forde-Thomas, J, Crusco, A, Cookson, A, Hollinshead, J, Fenn, C, Bartholomew, B, Holdsworth, PA, Fisher, M, Nash, RJ & Hoffmann, K 2018, 'An Abeis procera - Derived tetracyclic triterpene containing a steroid-like core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni' International Journal for Parasitology: Drugs and Drug Resistance, vol. 8, no. 3, pp. 465-474. https://doi.org/10.1016/j.ijpddr.2018.10.009
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