Professor Dr Ole Holger Petersen

Research Priorities: Pathophysiology of alcohol-related pancreatitis, intracellular calcium tunnels, IP₃ receptors, CRAC channel blockers as potential therapeutic treatment

Ole Petersen is a Danish-British physician and physiologist who researches the molecular foundations of the function and malfunction of the pancreas. Using electrophysiological methods, live-cell imaging, and high-resolution electron microscopy, he studies how energy production, enzyme secretion, and cell protection are interlinked and why this finely balanced system collapses in the case of disorders such as alcohol-related pancreatitis.

Early on, using patch clamp measurements, Peterson managed to show that certain ion channels are directly regulated by local calcium signals and form the basis of coordinated enzyme secretion. The calcium ions pass through a channel or tunnel within the cell and reach certain target areas without being immediately distributed throughout the entire cytosol. Under normal physiological conditions short, exactly localised calcium spikes arise, which initiate granule exocytosis. There, mitochondria buffer part of the calcium and at the same time increase their ATP production, an energy boost that fuels secretion.

Under pathological conditions, however, for example under the influence of alcohol metabolites, this architecture is destroyed. A central mechanism is the excessive activation of IP₃ receptors, to which the signal molecule inositol 1,4,5-trisphosphate (IP₃) binds. This leads to a continuous outflow of calcium ions from the endoplasmic reticulum. Consequently, the calcium tunnels lose their spatial precision, the signals spread in an uncontrolled manner throughout the entire cytosol, and intracellular vacuoles fill with calcium. There, trypsinogen is prematurely activated into trypsin, which initiates autodigestive tissue damage, as is characteristic for alcoholic pancreatitis.

In recent review studies, Ole Petersen describes in detail how sustained calcium overload destabilises mitochondrial homeostasis. An excessive intake of calcium ions results in the opening of transition pores in the inner mitochondrial membrane, the collapse of the membrane, and the abrupt end of ATP synthesis.  The resulting energy deficiency exacerbates the dysregulation and leads to necrotic cell death. A self-reinforcing cycle arises, which significantly determines the severity of acute pancreatitis.

CRAC channels (calcium release-activated channels) play a key role in this. They open when the intracellular calcium reservoirs are exhausted, and in pathology contribute considerably to sustained calcium overload. Using animal models, Ole Petersen has managed to show that pharmacologically blocking these channels curbs the pathological calcium dynamics and protects cells from necrosis. This makes CRAC channel inhibition a highly promising therapeutic approach for treating acute pancreatitis. In addition, Petersen investigates the role of calmodulin, the stabilisation of which protects further sensitive control points.

The basic researcher stresses how precise spatial and temporal signal patterns influence the function of the pancreas. By combining high-resolution imaging with biophysical measuring techniques, his work shows that the health and sickness of the organ are based on the same signal architecture, except that in the case of illness synchronicity, locality, and energetics lose their equilibrium. 

Ole Petersen’s research combines biophysical precision with major pathophysiological relevance. It has played an important role in helping us to understand the central mechanisms of pancreatic diseases and to pave the way for new therapeutic strategies.