Affiliated to research
I received my PhD from Uppsala University in 1997 and was headhunted to Pharmacia and very soon became head of the Endocrine Research Group. During 1997-2011 I was working in pharmaceutical companies both in Sweden (Pharmacia, Biovitrum) and UK (Prosidion Ltd), were I did translational research, developed clinical candidates, and obtained position as Director in Pharmacology and member of research steering groups. I joined Helleday lab in 2012 and has since then assisted Prof. Helleday in establishing the translational team that exists today. As responsible for the MTH1 project, I have, together with the team, successfully developed Karonudib that is presently investigated in clinical trials. I am a member of Dept. Oncology-Pathology steering group and deputy group leader in the Helleday lab.
Our lab is continuously working towards developing novel targeted therapies out of basic science findings. The multidisciplinary translational research group is focusing on understanding basic DNA repair and DNA-damage signaling pathways as well as nucleotide metabolism and developing novel drugs for anti-cancer treatments, and for treating inflammation/autoimmunity and virus infections.
The research aims are to i) purifying and targeting proteins in DNA repair and metabolism, ii) use probes and genetic tools to increase basic knowledge around target proteins and iii) translating basic research findings into new treatments tested in clinic.
One example how we taken an idea from bench to bedside:
Many DNA damaging anti-cancer drugs cause replication-associated DNA damage that kill cancer cells. This is an effective way of treating cancer, but the problem is that also normal cells are damaged. Our strategy is to exploit the high level of DNA damage and dysfunctional redox status in cancer cells and prevent the repair of these lesions and even cause more oxidative lesions in the cancer cells. Using DNA repair inhibitors, we can selectively introduce toxic DNA damage to cancer cells. We demonstrated how targeting MTH1 can be used to target cancer in general without causing toxicity to non-transformed cells(Gad et al, Nature 2014; Huber et al., Nature 2014) and we have developed the MTH1 inhibitor (MTH1i) karonudib (Karolinska NUDT1 inhibitor) (Warpman Berglund et al., Ann Oncol 2016) and progressed it through GMP manufacturing, formulation, GLP safety assessment, IMPD, Medical Product Agency and ethical approvals. Presently two clinical Phase 1 trials (one in patients with advanced solid malignancies and one in haematological cancers) with karonudib are on-going at Karolinska University Hospital. Pharmacology and biology are often more complex than originally thought, and we continue to deepen our understanding of the mechanism of action of our MTH1i and the role of MTH1 in cancer pathology.