CRISPR-based drug target discovery in cancer and autoimmunity – Research group Fredrik Wermeling

Using experimental systems and patient material, we study the immune system with specific interests related to autoimmune disease and cancer therapy.

CRISPR-based drug target discovery in cancer and autoimmunity

A major part of the different projects in the lab involves using CRISPR-based custom screens as a discovery platform to understand complex biological processes and to identify novel drug targets. To facilitate the design of these custom screens, we have developed a freely accessible web-based software called Green Listed. A review describing bioinformatics tools we use designing and analyzing hypothesis-driven CRISPR screens can be found in Iyer VS et al., 2020). Related CRISPR plasmids that we have deposited can be found at the non-profit repository Addgene.

Examples of how we work with CRISPR for discovery in vitro and in vivo is found in Shen Y et al., 2021, where we describe the Rapid CRISPR Competitive/RCC assay and the ImmunoCRISPR/iCR model system), as well as in Jiang L et al., 2021, Cancer Research, where we study the CRISPR DNA damage response).

Several projects in the lab also relate to our interest in signaling downstream of the IL-4 receptor (IL-4R). The basis for this interest was the unexpected finding that the expression of the IL-4R is essential for the activity of a drug (IVIG) used to treat patients with autoimmune disease and that the expression of this receptor is highly regulated during inflammation (Anthony RM et al., 2011, Nature, and Wermeling F et al., 2013, PNAS). More recently we published a study describing how IL-4 can affect neutrophils, and consequences of this in the autoimmune setting (Panda SK et al., 2020, PNAS).

Publications

Selected publications

Funding

  • The Swedish Research Council
  • Swedish Cancer Society (project grants, and Senior Investigator Award 2022)
  • Karolinska Institutet (Faculty Funded Career Positions)
  • Swedish Foundation for Strategic Research (Ingvar Carlsson Award 2013)
  • Wenner-Gren Foundations (Wenner-Gren Fellow program)
  • Magnus Bergvall Foundation
  • Jeansson Foundations
  • Professor Nanna Svartz Foundation
  • Alex and Eva Wallström Foundation for scientific research and education
  • King Gustaf V 80-Year Foundation
  • The Swedish Rheumatism Association
  • Clas Groshinsky´s Foundation
  • The Alfhild Aquilin and Karl Bensen Memorial Foundation, and the Gösta and Karin Wahmans Memorial Foundation
  • Åke Wiberg Foundation
  • Börje Dahlin Foundation