WIMAN LAB
Wiman Lab research

p53 biology · translational therapeutics

Wiman Lab

Karolinska Institutet

Welcome to our lab

Restoring the guardian of the genome

We study how p53 determines cell fate after DNA damage and develop therapeutic approaches to restore p53 function in tumours — from small-molecule reactivators to strategies for readthrough of nonsense mutations.
ResearchPublications

Principal investigator

Klas G. Wiman

Professor of Molecular Cell and Tumour Biology

Professor Klas Wiman has led research on TP53 for over thirty years, combining basic studies of p53 regulation with drug‑discovery efforts that produced compounds such as PRIMA‑1 and APR‑246/eprenetapopt.
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Programmes

Current research programmes

Figures from Zhang Q., Bykov V.J.N., Wiman K.G., Zawacka‑Pankau J. (Cell Death & Disease, 2018) — APR‑246/PRIMA‑1MET reactivation of mutant p53 (figures and data showing targeting of cysteines 124 and 277). PMC full‑text article.
01

Reactivating mutant p53 for cancer therapy

Therapeutic reactivation of mutant p53 proteins using small molecules (for example PRIMA-1 and APR-246) and understanding the multiple downstream mechanisms that result in tumour cell death.

Figure 1 from 'Rescue of non-sense mutated p53 tumor suppressor gene by aminoglycosides' (identification and readthrough efficiencies of TP53 nonsense mutations; demonstrates aminoglycoside-induced readthrough of common TP53 PTCs including R213X).
02

Pharmacological readthrough of TP53 nonsense mutations

Developing strategies to restore full-length functional p53 from TP53 nonsense alleles by pharmacological induction of translational readthrough.

Figure 1 from 'Targeting of Mutant p53 and the Cellular Redox Balance by APR‑246 as a Strategy for Efficient Cancer Therapy' (schematic and experimental data linking APR‑246/MQ activity to thioredoxin reductase targeting and redox perturbation).
03

p53, cellular redox balance and tumour microenvironment

Investigating how redox biology modulates p53 responses and how tumour-associated fibroblasts and extracellular signals affect p53-mediated drug responses.

Figure 4 from 'Wig‑1 regulates cell cycle arrest and cell death through the p53 targets FAS and 14‑3‑3σ' (experimental data showing Wig‑1 effects on p53 target genes involved in cell‑cycle arrest and apoptosis).
04

p53 control of cell-cycle arrest and apoptosis

Defining transcriptional and post-transcriptional mechanisms by which p53 induces cell-cycle arrest (for example via p21) or apoptosis (for example via PUMA, FAS), and how these pathways determine therapeutic outcome.

Selected publications

Recent and defining work

2018

p53 as a hub in cellular redox regulation and therapeutic target in cancer

Cell Chemical Biology

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2009

PRIMA-1 Reactivates Mutant p53 by Covalent Binding to the Core Domain (Lambert et al.)

Cancer Cell

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2013

APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase

PNAS

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2017

Human cancer-associated fibroblasts enhance glutathione levels and antagonise drug-induced prostate cancer cell death

Nature Communications

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2022

Translational readthrough of nonsense mutant TP53 by mRNA incorporation of 5‑Fluorouridine

Cell Death & Disease

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Opportunities

Join the team

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