Department of Medical Biochemistry and Microbiology

Paraskevi Heldin research group

Hyaluronan-CD44 signaling

The regulated biosynthesis of the glycosaminoglycan hyaluronan is crucial for normal homeostasis, whereas abnormal accumulation of hyaluronan under pathological conditions promotes inflammation and cancer progression. A huge diversity of signaling networks have been identified through which hyaluronan, as a common thread and costimulatory molecule, acts through receptor-mediated signaling and affects cellular behavior. In order to elucidate the biological functions of hyaluronan, one must understand its biosynthesis, uptake and turnover, and signaling through the hyaluronan binding proteins such as CD44.

Our aim is to elucidate the mechanisms (epigenetic and post-translational regulation) underlying the expression and activity of hyaluronan synthetic enzymes (HAS1, HAS2, HAS3). Furthermore, we aim to develop HAS2 inhibitors to suppress the excessive amounts of hyaluronan in pathogenesis, and generate CD44 antagonists to target hyaluronan-CD44 signaling during cancer progression and virus infection.

Understanding of the molecular events that promote the accumulation of hyaluronan in disease, may facilitate the design of therapeutic strategies and improve the outcome of patients.