Research projects

Early detection of diseases such as cancers, cardiovascular diseases, or neurodegenerative disorders is crucial for their effective treatment. The diagnosis of such diseases relies on specific biomarkers, with proteins playing a fundamental role. Among them, cytochrome c (Cc), a small hemeprotein of approximately 12 kDa, has emerged as a key biomarker, in particular for diseases associated with apoptosis and oxidative stress.

Under physiological conditions, Cc is primarily located in the mitochondrial intermembrane space, where it functions as an electron carrier between complexes III and IV of the respiratory chain. In contrast, under pathological conditions, Cc translocates to the cytoplasm, nucleus/nucleolus, and extracellular space. Our group has identified novel nuclear and cytoplasmic protein targets of Cc involved in the DNA damage response (DDR), unveiling a Cc-centered signaling network crucial for nuclear-mitochondrial regulation and communication.

The multifaceted role of Cc in cell death and signaling is regulated by post-translational modifications. Targeting Cc to mitigate dysregulated cell death in lung or breast cancers—whose prognosis correlates with serum Cc levels—and inhibiting acetylation of a Cc-specific lysine in prostate cancer present unexplored therapeutic opportunities. In collaboration with Prof. M. Hüttemann (Detroit, MI, USA), we have detected dimethylated Cc in patients with Acute Myeloid Leukemia (AML). The proposed project, LeuCyto, focuses on dimethylated Cc as a biomarker for AML and aims to develop innovative methods for early diagnosis and severity prediction in disease prognosis.

Accurate detection of both dimethylated and native Cc variants could significantly enhance diagnostic and prognostic methods. Despite advancements in techniques such as ELISA and Western blot, precisely measuring dimethylated Cc remains challenging. We propose using biosensors to simultaneously detect both Cc forms in serum, enabling a more accurate assessment of disease severity and prognosis, particularly in AML, where serum Cc levels correlate with treatment response and tumor relapse.