Romeo Ricci
Romeo Ricci is a full professor at the Medical Faculty of the University of Strasbourg and Senior Investigator at the IGBMC. He finished studies in human medicine at the University of Berne, Switzerland in December 1997. In 1998, he joined the University Hospital in Zurich, Switzerland at the Department of Pathology for two years with a focus on clinical and molecular pathology, where he also accomplished his medical thesis focusing on cancer genetics. In 2000, he joined the Research Institute of Molecular Pathology (IMP) in Vienna as a postdoctoral fellow in the research group of Prof. Erwin F. Wagner; a position, which was funded by a Marie Curie Individual postdoctoral fellowship. In the laboratory of Prof. Erwin F. Wagner at the Research Institute of Molecular Pathology (IMP) in Vienna, his work initially focused on the role of the stress-activated Activator Protein-1 (AP-1) members and the MAPK Jun-N-terminal kinase (JNK) in liver regeneration and carcinogenesis as well as arthritis. During this period, he also started to focus on molecular mechanisms involved in cardiovascular diseases and he was able to unravel for the first time particular functions of AP-1 in heart failure. Coronary artery disease resulting from atherosclerosis of the coronary arteries is one of the main causes of heart failure. After moving to the Cardiovascular Research Laboratory of Prof. Thomas F. Lüscher at the Institute of Physiology at University of Zurich in 2003, he decided to study cellular processes and molecular pathways regulating atherosclerosis, focusing on JNK signaling. This work led to the discovery that JNK2 is essential in foam cell formation, a key process in atheroma formation. In 2004, he built up his own independent research laboratory at the Institute of Cell Biology at ETH Zurich, which was awarded with an independent non-tenured Assistant Professorship for Molecular Biomedicine in March 2007 by the Swiss National Science Foundation (SNSF). As an independent investigator he started to study the role of p38 MAPKs that consist of four different genes. He recently identified the first non-redundant in vivo functions of the forth member of the p38 family, p38-delta and a new target of the latter kinase, protein kinase D (PKD).
Overall, Romeo Ricci’s research uncovered important novel stress-mediated molecular mechanisms that contribute to the understanding of heart failure, atherosclerosis and diabetes. Based on this work, new therapeutic options arised that are currently evaluated in collaboration with pharmacological companies. For his work, he obtained the EMBO Young Investigator Award in 2009 and an „ERC starting grant“ in 2011.
Regulation of TGN function in pancreatic beta cells: From metabolic homeostasis to diabetes
Sorting and packing of cargo, proper coating of vesicles and their subsequent detachment from the Trans-Golgi-Network (TGN) require complex and dynamic mechanisms. These are particularly important in specialized secretory cells in which specific cargo is transported in vesicles from the TGN to the plasma membrane for subsequent release. Appropriate insulin secretion from pancreatic β cells is fundamental to maintain glucose homeostasis in living organisms. Loss and dysfunction of β cells are key pathogenic factors in diabetes mellitus. We recently discovered that the MAPK p38δ inhibits Protein Kinase D (PKD)-mediated insulin granule fission at the trans-Golgi network, granule transport and release of insulin in vivo. This regulatory function in insulin secretion may become detrimental in diabetic subjects since lack of p38δ and enhanced PKD activity also protects from oxidative stress-induced β cell failure.
PKD has been shown to regulate lipid-modifying effectors at the TGN, which may impact on membrane dynamics and thus vesicle formation as well as secretion. PKD is recruited to TGN membranes by binding to diacylglycerol (DAG) where it can associate with ADP-ribosylation factor 1 (ARF1). ARFs, members of the Ras superfamily of small GTPases, are particularly interesting as they are involved both in vesicle budding and fission at the TGN.
Most recent work of our laboratory identified a novel PKD-dependent checkpoint mechanism that controls biogenesis of secretory granules at the trans-Golgi network (TGN). PKD activation is the initiating and limiting step that ensures functional vesicle detachment from the TGN in regulated secretion. Generation of defective transport carriers at the TGN could account for the commonly observed first and second phase insulin secretion defects in patients suffering from type 2 diabetes.
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