Dr. Joanna Zawacka-Pankau, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute

Heme - iron protoporphyrin IX, is a prosthetic group in a range of proteins that play critical role in sustaining cell homeostasis under. Hemoproteins play disparate biological functions including transport of gaseous molecules, electron transfer reactions, regulation of gene transcription and miRNA processing. The exact role of heme, thus of protoporphyrin IX (PpIX), in regulating key cellular processes is far from clear.

Protoporphryin IX is a fluorophore of exciting spectral properties, since it absorbs light at the maximum in the Soret band (λ=405 nm) and in the Q bands, including the region close to the infrared at λ=625 nm. It emits fluorescent signal at about 635 and 705 nm. Due to its spectral properties, high chemical stability and low systemic toxicity, PpIX and its derivatives, found the application in photodynamic therapy of cancer (PDT) as photosensitizers (PS).

Photodynamic therapy of cancer is a relatively new modality to treat solid tumors by PS that selectively accumulate in cancer cells but not in normal cells. Upon light excitation at specific wavelength (600-800 nm for clinically approved sensitizers), excited PS can release the access of energy to molecular oxygen and other biomolecules to induce reactive oxygen species (ROS). This promotes cell death, which is called Photodynamic therapy. Delivery of the light of higher energy, leads to the emission of light quantum, which can be detected by CCD camera. This is exploited in photodynamic diagnosis (PDD). PDT is applied in clinics across Europe and the USA, with about 300 clinical trials on-going for several tumor types. The exact mechanism of cell death upon PDT, even though the extensive research, remains to be elucidated.

My group have already characterized PpIX itself, without light excitation, as potent activator of p53 tumor suppressor in cancer cells (Zawacka-Pankau et al., J Biol Chem 2007, Zawacka-Pankau et al., submitted), therefore our research interests focuses on understanding the mechanism of cancer cell death upon treatment with clinically relevant porphyrins and PDT in cancers of very poor prognosis.