Emerging and Exploratory Research

In addition to our main research themes, we pursue several emerging and exploratory research initiatives that expand our expertise in drug delivery, transporter biology, and therapeutic development. The projects highlighted below represent ongoing research activities and collaborations.

OCTs and Multifunctional Metformin Derivatives

We have collaborated with Dr. Magdalena Markowicz-Piasecka (Medical University of Łódź, Poland) since 2016. The primary focus of this collaboration has been the development of multifunctional metformin derivatives and prodrugs with enhanced antidiabetic and anticoagulant properties compared with metformin itself. In addition, we have explored the potential of these compounds as anticancer agents and as inhibitors of acetyl- and butyrylcholinesterases.

More recently, our research has focused on the interactions of metformin and its derivatives with organic cation transporters OCT1–3 (SLC22A1–3). Building on this work, we are expanding our studies to other members of the SLC22 family as well as Multidrug and Toxin Extrusion (MATE; SLC47) transporters. Through these efforts, we aim to improve our understanding of transporter-mediated uptake and elimination of metformin-derived compounds and support the development of more effective therapeutic agents.

CAT1 & MCT1 for Brain Drug Delivery

In addition to LAT1 and OATPs, we are investigating the potential of Cationic Amino Acid Transporter 1 (CAT1, SLC7A1) and Monocarboxylate Transporter 1 (MCT1, SLC16A1) as targets for brain-targeted and intra-brain delivery of endogenous compounds in the form of novel transporter-utilizing prodrugs.

This research is conducted in collaboration with Professor Antti Poso (University of Eastern Finland) and Dr. Thales Kronenberger (University of Tübingen, Germany). The collaboration combines computational drug design with experimental studies to characterize transporter–substrate interactions and the transport mechanisms of newly designed compounds. Through this work, we aim to identify novel strategies for selective delivery to the brain and specific brain cell populations.

Novel Piezo1 Targeting Therapeutics

Since 2019, we have collaborated with Professor Tarja Malm (University of Eastern Finland, A.I. Virtanen Institute for Molecular Sciences) to develop novel compounds that modulate the activity of the mechanosensitive Piezo1 ion channel. The importance of Piezo ion channels in mechanosensation was recognized with the 2021 Nobel Prize in Physiology or Medicine awarded to David Julius and Ardem Patapoutian.

Recent studies from Professor Malm’s group have demonstrated that Piezo1 activation enhances microglial phagocytosis, reduces pro-inflammatory microglial activation, and improves lysosomal function, leading to increased amyloid-β clearance in both human and mouse models of Alzheimer’s disease.

Our collaborative research aims to develop novel Piezo1 agonists and investigate their therapeutic potential in neurodegenerative disorders and other diseases involving dysregulated inflammatory responses. As Piezo1 is expressed in multiple tissues, including the brain and lungs, it also represents an attractive multitarget therapeutic candidate. In the future, Piezo1-targeting compounds may offer new opportunities for treating complex conditions involving both pulmonary and neurological manifestations.

Novel PP2A-Targeting Therapeutics

In collaboration with Professor Timo Myöhänen (University of Helsinki), we are developing novel compounds that target protein phosphatase 2A (PP2A), a key regulator of cellular signaling pathways implicated in several human diseases.

PP2A is the major phosphatase responsible for dephosphorylating tau protein, and impaired PP2A activity has been linked to the pathological accumulation of hyperphosphorylated tau, a hallmark of several neurodegenerative diseases. Consequently, restoration or enhancement of PP2A activity represents a promising therapeutic strategy for treating neurodegenerative disorders and other diseases associated with PP2A dysfunction.

This collaboration, initiated in 2019, also involves computational modeling and structure-based drug design studies led by Dr. Maija Lahtela-Kakkonen (University of Eastern Finland, School of Pharmacy). By combining medicinal chemistry, molecular modeling, and neurobiology, we aim to identify novel PP2A-targeting compounds with disease-modifying potential.