is awarded the prize/grant 2017 for his work on the development and characterization of physiological hepatic model systems with the goal to study the molecular basis underlying inter-individual differences in drug response.
Volker M. Lauschke received his Ph.D. from the EMBL and the Combined Faculty of Natural Sciences and Mathematics of the University of Heidelberg in 2013 for his work on tissue patterning using molecular oscillators. In 2014, he moved to Karolinska Institutet (KI) as a MarieCurie fellow to work on the development and characterization of physiological hepatic model systems with the goal to study the molecular basis underlying inter-individual differences in drug response. After 2 years of postdoctoral studies at KI, Volker became Assistant Professor in Liver Function and Regenerationat the Department of Physiology and Pharmacology in 2017.
Life is dynamic
How a single cell develops into a fully functional organism is one of the central questions in biology. During development, patterning of the embryo must be tightly coordinated to changes in its overall size. This phenomenon of maintaining proportionality between developing structures, termed scaling, requires that cells have information about their relative position within a tissue.
In my doctoral studies I developed a primary cell culture assay in which scaling could be observed in an experimentally accessible in vitro context. Using this platform I found that spatial information can be encoded using two molecular oscillators with distinct kinetics. One oscillator is phase-shifted between neighboring cells resulting in gene activity waves sweeping across the tissue; the other is a globally synchronized reference oscillator. A famous analogy to this concept is the solution to the longstanding problem of longitude measurements in navigation. Here, the phase-shift between two clocks, one reference clock set to Greenwich time and one set to local time, was used to decode spatial, i.e. longitude coordinates.
These findings, published in Nature and distinguished as a Research Highlight in Nature Genetics and with a dedicated News and Views report in Nature, prompted a change in perspective as they revealed a conceptually distinct mechanism for positional information and scaling that utilizes phase-shifted oscillators to directly and naturally encode spatial cues in a biological system.
Recapitulating complex physiological processes in vitro
The liver has a unique regenerative capacity that is tightly linked to the capability of hepatocytes to rapidly respond to various signaling molecules or changes in environment. Whereas hepatocytes are functionally highly specialized and do not divide under homeostatic conditions, upon liver damage, they transiently lose expression of key hepatic genes and dedifferentiate into fetal-like progenitor cells, which enter the cell cycle to regenerate the damaged tissue. Once cells sufficiently proliferated, they redifferentiate again into mature, fully functional hepatocytes.
In my postdoctoral studies as a Marie Curie fellow, I have applied my knowledge in ex vivo primary cell culture systems and cellular signaling to contribute to the development of a 3D spheroid culture system for primary human hepatocytes in which cells remain viable and functionally stable for multiple weeks. Strikingly, in this system cells first lose their hepatic characteristics during the initial aggregation phase but regain them after spheroids formed, providing an ideal ex vivo experimental paradigm to study the full spectrum of differentiation state changes that occur in vivo during liver regeneration.
My research group tries to elucidate the mechanistic underpinnings that grant hepatocytes their unique plasticity. To this end, we employ a multidisciplinary approach combining integrative multi-dimensional omics analyses for hypothesis generation with targeted experiments in vitro and in vivo to functionally test interesting findings. In addition, we aspire to utilize the obtained knowledge to develop approaches to generate functional hepatocytes in vitro that can be utilized for autologous transplantation purposes.
I am deeply grateful to have been granted the Malin och Lennart Philipson Award 2017. During my predoctoral studies I had the pleasure to experience the inclusive, approachable and open-minded spirit that he managed to evoke at EMBL and which coined so many scientists throughout Europe and worldwide, including myself. I feel honored to receive a prize in Lennart’s name and will strive to contribute to the dissemination of his scientific leadership philosophy.