Stig Linder's Group
Our group works in the area of drug development and cancer pharmacology.
A main focus of our research group is to identify new inhibitors of the ubiquitin-proteasome system (D'Arcy, Brnjic et al., Nature Medicine 2011; Mofers et al., Eur J Pharmacol. 2020). The molecules b-AP15/VLX1570 inhibit two deubiquitinating enzymes (USP14/UCHL5) in the 19S proteasome. We and other groups have shown that these substances exhibit significant antitumor activity in various tumor models. By using combinations of different methods, we aim to understand the molecular mechanisms of action of our molecules (Gubat et al., Front Oncol. 2022). We hope that drugs can be developed that can be used to treat multiple myeloma resistant to the proteasome inhibitor Velcade®. Through the use of CRISPR loss-of-function screens, we aim to understand the importance of different deubiquitinases for the viability of cancer cells with different genetic backgrounds.
Using tumor cells grown in 3-D culture (multicellular spheroids), we have shown mitochondrial metabolism is essential for cells growing in starved and hypoxic regions (Zhang et al., Nature Communications 2014). Our results show that tumor cells in such regions have limited capacity for metabolic plasticity and we are working to identify drugs that can be used for the treatment of solid tumors, mainly advanced ovarian cancer (Zhang et al., Int J Mol Sci. 2021).
Mechanistic studies of a novel inhibitor of the ubiquitin-proteasome system
Inhibition of 19S proteasome deubiquitinases as a promising strategy in cancer therapy
Tumor acidosis in malignant progression and therapy
Development of therapeutic strategies for quiescent tumor cell populations
Different approaches to develop radio- and chemotherapy for treatment of human cancer
Studies of overcoming acquired resistance: molecular mechanisms and development of novel drugs
Identification and characterization of a proteasome deubiquitinase inhibitor
Using a 3-d model system to screen for drugs effective on solid tumors
On the role of different signal transduction pathways in induction of apoptosis by anticancer drugs
Maria Hägg Olofsson
Translational studies of drug-induced tumor cell death
Characterization of the mechanisms of action of anticancer agents in vitro and monitoring their effects in vivo
Analyses of the expression and function of the aspartic protease napsin
On the role of SAP kinase pathways in cellular responses to cancer treatment
Elucidation of pro-apoptotic signaling induced by cisplatin
The prognostic significance of uPA, uPAR and the cytokine IL-1-alpha in urinary bladder cancer