Professor Karl Hoffmann

Title: Development and use of enabling technologies to accelerate schistosome drug discovery

Abstract:

Schistosomiasis is a neglected tropical disease that affects hundreds of millions of people living in some of the most resource-poor communities in the world.   Individual and community-level control primarily relies on praziquantel, a WHO-recognised essential drug that has well-recognised limitations (i.e. inactivity against juvenile worms, compromised efficacy by immunodeficiency and low cure rates in high transmission areas). Should schistosomes develop insensitivity or resistance to PZQ, schistosomiasis control would be substantially compromised.

Over the last decade, we have established high-throughput, whole-organism phenotypic platforms to facilitate screening of large compound collections against schistosomes. Our goal, using these platforms, is to bring new chemical matter into the schistosome drug discovery pipeline for progression as new PZQ replacements or for use in combination with PZQ.  While we have completed >500K individual screens and identified incredibly potent compounds, our progress in translating these promising ex vivo results into in vivo efficacy has been slow.  

We contend that embedding enabling technologies into our pipeline will not only increase the pace of drug discovery, but will also focus (often limited) resources around tractable chemical matter/protein target pairings. Here, using examples derived from ongoing projects, I will present how complementary strategies are being developed and deployed in our laboratory to accelerate the search for novel anti-schistosomals.

Bio:

Karl completed his PhD in Pharmacology and Molecular Science at the Johns Hopkins University School of Medicine, USA in 1997.  Afterwards, he moved to the National Institutes of Health in Bethesda, USA where he completed a three-year post-doctoral fellowship in the Laboratory of Parasitic Diseases.  In 2000, Karl was awarded an EMBO long-term research fellowship to move across the pond to the Department of Pathology, University of Cambridge, UK.  After completing his EMBO fellowship, Karl remained in Cambridge where he began building his own research group with funding provided by Wellcome as part of a Career Development Award (202-2007).  In 2007, Karl relocated his laboratory to Aberystwyth University, UK where he currently holds a chair in Parasitology and leads the Parasite Research Group and the Barrett Centre for Helminth Control.

Since joining Aberystwyth University, Karl has focused on strategies to control parasitic worms (helminths) of biomedical, veterinary and zoonotic importance.  His team identifies parasite vulnerabilities derived from gene-level studies of developmental biology and exploits these as part of new drug or vaccine pipelines. He has been awarded research funding from Wellcome, the BBSRC, the European Research Council, the Global Health Innovative Technology fund, the Welsh Government, the Nuffield Foundation, Innovate UK and human as well as animal health companies.  Karl welcomes the opportunity to collaborate with others in the pursuit of new anthelmintics against both blood (Schistosoma sp) and liver (Fasciola hepatica) flukes.

First published: 4 September 2025

<< Seminars