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Karolinska institutet
Karolinska universitetssjukhuset

Fredrik Wermeling Team

CRISPR-based drug target discovery in cancer and autoimmunity


Our research focuses on studying the immune system using experimental systems and patient material, with specific interests in autoimmune disease and cancer therapy. One of the key components of the lab’s projects involves utilizing custom CRISPR-based tools as a discovery platform to gain insights into complex biological processes and identify novel drug targets.

To aid in the design of custom CRISPR screens, we have developed a freely accessible web-based software called Green Listed (published in Panda SK et al., Bioinformatics, 2017). For more information on the bioinformatics tools we employ in designing and analyzing custom, hypothesis-driven CRISPR screens, please refer to the review by Iyer VS et al. (CSBJ, 2020). Additionally, relevant CRISPR plasmids that we have generated can be found at the non-profit repository Addgene.

We have successfully utilized CRISPR technology for discovery both in vitro and in vivo: In Shen Y et al. (CSBJ, 2021), we describe the Rapid CRISPR Competitive (RCC) assay and the in vivo ImmunoCRISPR (iCR) model system. In Jiang L et al. (Cancer Research, 2021) we used a pooled custom CRISPR screen approach to study consequences of CRISPR-Cas9 mediated DNA damage response in the context of cancer. In Panda SK et al. (PNAS, 2020), we identified an IL-4R regulating factor using an arrayed custom CRISPR screen.

Another focus area of the lab relates to signaling downstream of the IL-4 receptor (IL-4R). Our interest in this field stems from the intriguing discovery that the expression of the IL-4R is critical for the efficacy of IVIG, a drug used in autoimmune disease treatment Anthony RM et al. (Nature, 2011). Moreover, we have observed that the expression of this receptor undergoes tight regulation during inflammation, as reported in Wermeling F et al. (PNAS, 2013). Importantly, in Panda SK et al. (PNAS, 2020), we described the involved mechanism. Currently, we are exploring this signaling pathway as a therapeutic modality in cancer.

Our research projects have a collective goal of expanding our knowledge of the immune system, autoimmune disease, and cancer therapy. Ultimately, our goal is to improve patient outcomes and provide new treatment options in these fields.

Team leader

Fredrik Wermeling, Principal researcher, Associate professor, fredrik.wermeling@ki.se.

PhD: Karolinska Institutet, Stockholm. Postdoc: Rockefeller University, New York.

Wenner-Gren fellow, 2010-2015. Ingvar Carlsson Award 2013. Cancerfonden Senior Investigator Award, 2022.

Team members

Zsolt Kasza, Lab manager, PhD, zsolt.kasza@ki.se.

Yunbing Shen, PhD student, MSc, yunbing.shen@ki.se.

Zhaojun Li, PhD student, MSc, zhaojun.li@ki.se.

Sanjay Boddul, Associated, PhD, sanjay.boddul@ki.se.


Vaishnavi Srinivasan Iyer, PhD student. PhD 2022.

Long Jiang, PhD student. PhD 2022.

Gustaf Wigerblad, Postdoc.

Yanek Jiménez-Andrade, Postdoc.

Sudeepta Kumar Panda, Postdoc.

Sergio Haller, Postdoc.

Selected publications

Modulating T-cell activation with antisense oligonucleotides targeting lymphocyte cytosolic protein 2.
Iyer VS, Boddul SV, Johnsson AK, Raposo B, Sharma RK, Shen Y, Kasza Z, Lim KW, Chemin K, Nilsson G, Malmström V, Phan AT, Wermeling F
J Autoimmun 2022 Jul;131():102857

CRISPR/Cas9-Induced DNA Damage Enriches for Mutations in a p53-Linked Interactome: Implications for CRISPR-Based Therapies.
Jiang L, Ingelshed K, Shen Y, Boddul SV, Iyer VS, Kasza Z, Sedimbi S, Lane DP, Wermeling F
Cancer Res 2022 01;82(1):36-45

A rapid CRISPR competitive assay for in vitro and in vivo discovery of potential drug targets affecting the hematopoietic system.
Shen Y, Jiang L, Iyer VS, Raposo B, Dubnovitsky A, Boddul SV, Kasza Z, Wermeling F
Comput Struct Biotechnol J 2021 ;19():5360-5370

In vitro and ex vivo functional characterization of human HLA-DRB1∗04 restricted T cell receptors.
Boddul SV, Sharma RK, Dubnovitsky A, Raposo B, Gerstner C, Shen Y, Iyer VS, Kasza Z, Kwok WW, Winkler AR, Klareskog L, Malmström V, Bettini M, Wermeling F
J Transl Autoimmun 2021 ;4():100087

Designing custom CRISPR libraries for hypothesis-driven drug target discovery.
Iyer VS, Jiang L, Shen Y, Boddul SV, Panda SK, Kasza Z, Schmierer B, Wermeling F
Comput Struct Biotechnol J 2020 ;18():2237-2246

IL-4 controls activated neutrophil FcγR2b expression and migration into inflamed joints.
Panda SK, Wigerblad G, Jiang L, Jiménez-Andrade Y, Iyer VS, Shen Y, Boddul SV, Guerreiro-Cacais AO, Raposo B, Kasza Z, Wermeling F
Proc Natl Acad Sci U S A 2020 02;117(6):3103-3113

Green listed-a CRISPR screen tool.
Panda SK, Boddul SV, Jiménez-Andrade GY, Jiang L, Kasza Z, Fernandez-Ricaud L, Wermeling F
Bioinformatics 2017 04;33(7):1099-1100

Acute inflammation primes myeloid effector cells for anti-inflammatory STAT6 signaling.
Wermeling F, Anthony RM, Brombacher F, Ravetch JV
Proc. Natl. Acad. Sci. U.S.A. 2013 Aug;110(33):13487-91

Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway.
Anthony RM, Kobayashi T, Wermeling F, Ravetch JV
Nature 2011 Jun;475(7354):110-3

Invariant NKT cells limit activation of autoreactive CD1d-positive B cells.
Wermeling F, Lind SM, Jordö ED, Cardell SL, Karlsson MC
J. Exp. Med. 2010 May;207(5):943-52


All publications by Fredrik Wermeling found at PubMed

The Wermeling lab at the Karolinska Institutet

Greenlisted CMM

About CMM

The Center for Molecular Medicine (CMM) is a foundation instituted by the Stockholm County Council (Region Stockholm). CMM is at the heart of a close partnership with the Karolinska University Hospital and Karolinska Institutet, fueling advancements in biomedical and clinical research.


Center for Molecular Medicine Foundation, org. nr. 815201-3689

Karolinska University Hospital L8:05

Visionsgatan 18

171 76 Stockholm, Sweden


Karolinska institutet
Karolinska universitetssjukhuset