Roman Meledin

Many processes in our body depend on growth factors, hormones and cytokines. These molecules exert their function via certain signaling pathways. Overactivation of this signaling is associated with autoimmune diseases and lymphoproliferative cancer. Drugs can restore an imbalanced signaling, however, their development necessitates a robust measurement of pathway activation. 

 Janus kinase (JAK) - signal transducer and activator of transcription (STAT) is a prominent pathway regulating the activation, proliferation and survival of many different cells, including cells of immune system.  Direct, continuous, and real-time measurement of JAK-STAT activation in live cells would offer valuable insights into the kinetics and dynamics of inhibition and help minimize perturbations between measurements. Currently, however, all used approaches are non-continuous, excluding the real-time monitoring of STAT activation in live cells, and therefore limiting the progress of JAK-STAT inhibitor development. 

Roman Meledin and his STATcovery team address this need by developing and implementing genetically encoded biosensors designed for real-time monitoring of STAT activation. Their design principles utilize Fluorescence Lifetime Microscopy (FLIM)-Förster Resonance Energy Transfer (FRET) to precisely measure the activation of JAK-STAT signaling by detecting conformational changes of STATs. 

During his Fellowship, Roman will expand the biosensor repertoire to cover all human STATs, engineer stably transfected cell lines with integrated biosensors, and improve the setup for straightforward and user-friendly sample acquisition. To validate and apply the technology in real-world scenarios he is setting up collaborations with academic institutions and potential customers, including pilot projects with pharma partners. 

The ultimate goal is to bring STAT biosensors to the market to support drug development and fundamental research on JAK-STAT signaling pathways. The new products have the potential to make a significant contribution to both cell-based assays and the JAK-STAT drug markets. The primary market includes drug discovery and preclinical research departments in pharmaceutical and biotechnology companies focused on oncology, immunology, and inflammation research. 

Affiliation: Prof. Onur Boyman 

Start date: 09/2024