I am fascinated by working at the interface of protein science, biophysics, molecular medicine, biophotonics and proteomics. My focus is on protein biophysics, protein structure and the complex and fascinating interplay between proteins and light.

Key pharmaceutical proteins have been investigated (insulin, EGFR, plasminogen) and data shows that protein structure can be modulated by light leading to activation or deactivation of protein function. My goal is to use such knowledge for modulating protein function and metabolic pathways with light, e.g. to modulate key ligand-receptor interactions at the cellular level to develop a new cancer therapy (vide infra). Aside from resulting in exciting new basic science insights, my work has led to the development of a new protein covalent photonic immobilization technique, successfully been used to design and engineer drug delivery systems and biosensors at the micro and even at nanoscale, the latter made possible using multiphoton excitation and nanoplasmonics effects in a hotspot. The technology, relevant to cancer diagnostics and to the detection of cardiovascular disease markers, is being used in two Horizon2020 EU projects.

The study of the complex interplay between the protein molecule and light led to the development of a new photonic cancer therapy, demonstrating how low dose 280nm light can disable cancer cells. My group has shown that UV light chemically modifies the same receptor protein, Epidermal Growth Factor Receptor (EGFR), that many cancer therapeutic treatments are trying to target chemically. EGFR plays a key role in regulating cell survival, proliferation and migration. Its overexpression and activation have been correlated with cancer progression.

We show that low dose UV illumination induces structural changes in EGFR and halts its activation by the epidermal growth factor, thereby blocking downstream reactions, key EGFR dependent signaling pathways and cancer proliferation. Illumination of adenocarcinomic human alveolar basal epithelial cells (Human A549 – EGFR biosensor cell line) with 280 nm at irradiance levels up to 20 times weaker than the UVB solar output for short periods of time (15-45 min) prevents EGF-mediated activation of EGFR located on the cell membrane, preventing or reducing cellular disaggregation, formation of filopodia and cell migration. Filipodia formation is a phenomenon observed after the activation of EGFR by the epidermal growth factor and contributes to cancer metastization. This effect of UV light illumination was confirmed further in a functional scratch assay and recent published data shows that the photonic therapy is more effective than therapies a using specific EGFR-signaling inhibitor (Tyrphostin AG1478, a tryrosine kinase inhibitors). This new photonic approach may be applicable to the treatment of various types of cancer, alone or in combination with other therapies. Taking this technique from the bench to the clinical practice would be straightforward when compared to other photonic based techniques, as little secondary or deleterious effects are foreseen when using such low power of light.

• “Photonic Arrest of Cancer Metastization” CM. Botelho, et al. J. Biophotonics 2018 DOI: 10.1002/jbio.201700323
• “Modulating the Structure of EGFR with UV Light: New Possibilities in Cancer Therapy” Correia et al. PLoS ONE 2014 9(11): e111617. doi:10.1371/journal.pone.0111617
• “UV light blocks EGFR signalling in human cancer cell lines” Neves-Petersen et al. Int Journal of Oncology 30(1), 181-185 (2007).
• “Plasmon-assisted delivery of single nano-objects in an optical hot-spot.” Galloway et al, Nano Letters, 5, 8874-8878 online DOI: 10.1021/nl402071p, 2013.

Host: Professor Daniel Otzen, iNANO and Dept. of Molecular Biology and Genetics, Aarhus University