Volker Lauschke

Volker Lauschke

Professor | Docent
Telephone: +46852487711
Mobile phone: +46704926778
Visiting address: Solnavägen 9, Biomedicum, 17165 Solna
Postal address: C3 Fysiologi och farmakologi, C3 FyFa Individanpassad medicin och läkemedelsutveckling, 171 77 Stockholm

About me

  • Volker M. Lauschke (V.M.L.) is Professor in Translational Pharmacology at Karolinska Institutet (KI), Stockholm, Sweden and Director of the Biofabrication and Tissue Engineering Facility at KI. He is also Deputy Head of the Margarete Fischer-Bosch Institute of Clinical Pharmacology in Stuttgart, Germany. The research group integrates 3D cell culture systems of primary human cells, microfluidics and comprehensive molecular profiling technologies to discover novel therapeutic strategies for inflammatory conditions (NASH), infectious diseases (COVID-19 and hemorrhagic fevers) and complex metabolic diseases (type 2 diabetes). In addition, we use population-scale genomics and machine learning tools to map the ethnogeographic variability in genes involved in drug absorption, distribution, metabolism and excretion, as well as drug targets with a specific focus on the contribution that rare genetic variations play in drug response and toxicity and how this information can improve personalized medicine and precision public health. V.M.L. has authored over 160 papers in peer-reviewed journals and is the recipient of multiple awards in the area of genetics, pharmacology and drug discovery, including the Malin and Lennart Philipson Prize 2016, the AAPS High Impact Award 2020 and the ISSX Karl Netter Award 2023. Furthermore, he is among the Clarivate Highly Cited Researchers in Pharmacology 2022 (1 of 3 in Sweden). Besides his academic work, he is co-founder and CEO of HepaPredict AB, a biotech company offering 3D human liver models for drug discovery and development, as well as co-founder and CSO of PersoMedix AB, providing services for personalized drug response predictions. Professional Experience Since 2023: Professor in Translational Pharmacology (Karolinska Institutet, https://ki.se/en/fyfa/lauschke-lab) Since 2021: Deputy Head of the Margarete Fischer-Bosch Institute of Clinical Pharmacology (Stuttgart, Germany, http://www.ikp-stuttgart.de/content/language1/html/16655.asp) Since 2018: Director of the Biofabrication and Tissue Engineering Core Facility (https://ki.se/en/fyfa/biofabrication-and-tissue-engineering-biofab-faci?) Since 2018: Docent in Pharmacology 2018 - 2023: Associate Professor in Personalized Medicine and Drug Development (Karolinska Institutet) 2017 - 2018: Assistant Professor in Liver Function and Regeneration (Karolinska Institutet) 2014 - 2016: Postdoctoral Research Associate and MarieCurie Fellow (Karolinska Institutet) 2013 - 2014: Bridging Postdoctoral Research Associate (EMBL Heidelberg, Germany) Education 2016 - 2018: Master of Science in Business Administration and Economics (University of Hagen, Germany) 2012 - 2016: Bachelor of Science in Business Administration and Economics (University of Hagen, Germany) 2009 - 2013: Dr. rer. nat. / PhD studies (EMBL Heidelberg, Germany) 2007 - 2009: Master of Science in Molecular Biosciences (University of Heidelberg, Germany) 2004 - 2007: Bachelor of Science in Molecular and Cellular Biology (University of Heidelberg, Germany and University of Bergen, Norway) Fellowships, Prizes and Awards 2023 ISSX Karl Netter Award 2022 Clarivate Highly Cited Award in Pharmacology 2020 High Impact Award by the American Association of Pharmaceutical Scientists (AAPS) 2017 Lennart Philipson Prize 2014 Marie Curie Fellowship 2009 Top Master of Science (M.Sc.) Award 2006 Erasmus Fellowship Current and recent funding NovoNordisk Project grant, NovoNordisk Pioneer Grant, Data-driven Life Science Program, ERC Environment & Health Grant NEMESIS, ERC Synergy Grant SPHERES, IMI2 EUbOPEN, VR Project Grant, VR Consolidator Grant, KI Consolidator Grant, Rolf Luft Grant in Diabetes Research, SFO Stem Cells and Regenerative Medicine, Lennart Philipson Research Grant. We furthermore acknowledge support from Merck KGaA, Eli Lilly and Company and the Robert Bosch Foundation. Editorial Activities - Editorial roles: The Pharmacogenomics Journal (Associate Editor since 2022, Board Member 2020-2022), Human Genomics (Executive Associate Editor since 2024, Associate Editor 2020-2022, Board Member 2017-2020), Computational & Structural Biotechnology Journal (Associate Editor since 2020), Annals of Human Genetics (Senior Editor since 2019) - Editorial Board Member: Pharmacological Reviews (Since 2023), Frontiers in Pharmacology (Since 2017), Frontiers in Medicine (Since 2018), Drug Metabolism Reviews (Since 2019), Current Drug Metabolism (Since 2019), Current Research in Pharmacology and Drug Discovery (Since 2020), Pharmacogenomics Research and Personalized Medicine (Since 2020), Precision Cancer Medicine (Since 2020) - Guest Editor of Special Issues in Human Genomics ("Pharmacogenomics beyond single common genetic variants", June 2023), Journal of Clinical Medicine ("Importance of Genetic Variants for the Hepatic Metabolism of Xenobiotics", June 2020) and Frontiers in Genetics ("Population Pharmacogenomics: From Variant Identification to Clinical Implementation", Dec 2020) Current group members Sonia Youhanna (Postdoctoral Researcher) Shane Wright (Postdoctoral Researcher) Nayere Taebnia (Postdoctoral Researcher) Sabine Willems (Postdoctoral Researcher) Yi Zhong (Postdoctoral Researcher) Reza Zandi Shafagh (Postdoctoral Research Engineer) Xuexin Li (Senior Researcher) Isabel Barragan (Senior Researcher) Nuria Oliva-Vilarnau (PhD Student) Aurino Kemas (PhD Student) Jibbe Keulen (PhD Student) Mahamadou Camara (PhD Student) Stefania Koutsilieri (PhD Student)

Research

  • Development of microphysiological 3D tissue models. We previously established an integrated 3D spheroid cell culture system for primary human hepatocytes (PHH) in which cells faithfully mimics hepatic phenotypes in vivo and can be utilized for long-term analyses of drug metabolism, liver function and regulation. In addition we develop 3D tissue models for human adipose tissue, pancreatic islets and skeletal muscle and carefully benchmark the cultured cells to their corresponding counterparts in situ using an array of omics techniques. Novel therapeutic strategies against non-alcoholic steatohepatitis (NASH) Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease with a global prevalence of 24% in the general adult population. Onset of NAFLD is hallmarked by the accumulation of lipids within hepatocytes. This initially benign steatosis can develop into NASH, an inflammatory condition in which liver macrophages (Kupffer cells) are increasingly activated and secrete excessive amounts of pro-inflammatory cytokines, which further progresses into liver fibrosis and cirrhosis in approximately 20% of NASH patients. Despite substantial efforts, there are very limited treatment options for NASH. Furthermore, the lack of validated biomarkers in NASH that predict the development of liver-related morbidity and mortality hinder progress in drug development. We have previously established a 3D spheroid culture system for primary human liver cells in which hepatocytes and non-parenchymal cells (NPCs), including stellate and inflammatory Kupffer cells, remain viable and functional for ≥5 weeks in culture. Importantly, physiological crosstalk between hepatocytes and NPCs is maintained in vitro and we could show that nutritional perturbations can induce hepatic insulin resistance and steatosis. We have recently succeeded in extending the system by directly using cryopreserved hepatocytes and NPCs from NASH patients and could show that key disease aspects including extensive oxidative stress, inflammation and fibrosis are recapitulated in vitro. Furthermore, using chemogenomic screening of a library of chemical probes with well-characterized specificity profiles accessible via the Structural Genomics Consortium, we could identify multiple novel pharmacologically accessible targets that reduce steatosis or fibrosis. Mechanistic follow-ups investigations into hits are currently ongoing. Facilitating the development of micro- and nanofabrication technologies for scalable drug development For nearly three decades, microfluidic and organ-on-a-chip models are still heavily reliant on polydimethylsiloxane (PDMS) soft lithography. While these methods allow the easy fabrication of cell compatible devices, PDMS soft lithography suffers from long cycle times, limited scalability and substantial absorption of hydrophobic molecules. As a consequence, the translation of micro- and nanodevices from the research setting to industrial applications remains limited. To overcome these limitations, we develop micro- and nanofabrication technologies using novel polymers in our on-site state-of-the-art cleanroom facilities. We have developed nanoimprint lithography (NIL) and Nano Reaction Injection Molding of a novel polymer with low drug absorption, off-stoichiometry thilo-ene (OSTE), that allow for rapid and cost-effective fabrication of polymer micro- and nanodevices. By uncoupling ultra-high resolution multiplanar polymer structuring from complex processing conditions, we provide accessible and versatile technologies for the fabrication of devices for a wide range of applications in biology, medicine and physics that already support a multitude of research groups at Karolinska. Microfluidic human ex vivo models for complex metabolic phenotypes Type 2 diabetes (T2D) is the most prevalent metabolic disorder that manifests due to a dysfunctional interplay of multiple tissues and organs. T2D constitutes a globally increasing health problem that affects 450 million individuals worldwide, which is expected to rise to 592 million by 2035. Although diabetes care has improved, complications are still common, and diabetes remains a leading cause of cardiovascular morbidity, visual loss, amputation, and end-stage renal disease. By integrating our custom-designed microfluidic systems with human tissue models, we develop MPS in which 3D microtissues can be cultured with in vivo-like molecular phenotypes and tissue-specific functionality for multiple weeks, thus allowing to investigate tissue interactions upon nutritional and pharmacological perturbations. Specifically, we have developed devices with pneumatic actuation that allow for long-term communication between 3D primary human tissue models. We furthermore integrate 3D tissue models of liver, pancreas, adipose tissue and skeletal muscle to develop integrative human MPS to study mechanisms underlying glycemic control. Rational drug biasing Bioluminescence resonance energy transfer (BRET)-based biosensors have been used extensively to characterize signal transduction events using recombinant expression in human cell lines. While these experiments are useful to reveal possible ligand and receptor bias, they do not allow to study signaling in a physiological context. We have established a battery of biosensors for all human G-proteins as well as a suite of organelle markers to investigate signaling in primary human 3D tissue cultures. We observed that clinically approved compounds targeting the receptors differ with regards to signaling dynamics and their signatures of downstream G-protein/β-arrestin activation. Dual incretin receptor agonism constitutes an emerging strategy for the treatment of diabetes and obesity that has recently been demonstrated to also improve NASH. Combining our BRET biosensors with patient-derived material aspires to provide much needed insight into the intra- and inter-patient variability of drug action and offers the potential to develop better and more targeted therapies that effectively balance insulin stimulation with the hyperglycemic effects of GCGR agonists. Furthermore, by combining these tools with structural approaches we aim to develop compounds with specific bias, which opens new avenues to optimize drug efficacy and minimize side effects also for other G-protein coupled receptors. Individualized precision drug development Inter-individual differences in drug response constitute major challenges for drug development and clinical therapy. We will profile the differences in molecular phenotypes of 3D human tissue cultures and compare pharmacological effects between donors. For these efforts, we focus on high-throughput compatible models of liver, adipose tissue and pancreatic islets to screen for hit compounds across donors. For instance, the GLP1R agonists semaglutide and liraglutide are used in type 2 diabetes to increase insulin secretion to control glycemia
  • however, effects differ considerably between patients. By treating human islets from non-diabetic, prediabetic and diabetic individuals ex vivo, we investigate response biomarkers that can facilitate patient stratification and the development of companion diagnostics. Similar assessments of inter-individual differences in drug response are planned for insulin sensitizers and sulfonylureas, as well as for treatments for NASH and infectious diseases. Mechanistic analysis and pharmacological modulation of human liver regeneration To study the molecular biology of liver regeneration, particularly the rodent hepatectomy model serves as the main experimental paradigm. In this model, the majority of remaining hepatocytes re-enter the cell cycle within 24 hours, which is in stark contrast to homeostatic conditions, under which hepatocytes are quiescent with an average lifespan of 200-400 days. By integrating organotypic 3D spheroid cultures of primary human or murine hepatocytes with chemogenomic screening, we have revealed striking species differences in the molecular control of hepatocyte regeneration. Specifically, we found that growth factors are the main mitogens in rodents, while activation of Wnt/β-catenin signaling is the major driver in human hepatocytes. We furthermore identify TGFβ inhibition and inflammatory signaling via NFκB as essential steps for the quiescent-to-regenerative switch that allows Wnt/β-catenin-induced proliferation of human cells. High-throughput chemogenomic screening furthermore revealed critical roles of the Polycomb Repressive Complex 2 (PRC2), as well as of the bromodomain families I, II and IV in controlling cell cycle re-entry and proliferation of primary human hepatocytes. These results are conceptually important as they extend our mechanistic understanding of human liver regeneration, demonstrate the potential of organotypic human culture systems for the chemogenomic interrogation of complex physiological processes and open new possibilities for the development of therapeutic approaches as a substitute for orthotopic liver transplantations. Bioprinting 3D bioprinting in which biocompatible materials together with cells and supporting components are patterned into complex functional tissue constructs is enabling new applications in many areas of research. Bioprinting facilitates the high-throughput generation of biomimetic tissue models for personalized medicine, drug discovery, and toxicology using patient-derived material. 3D bioprinting is also applied in regenerative medicine to address the scarcity of tissue and organ transplants. We have received infrastructure support for the acquisition of a state-of-the-art bioprinter to facilitate spatially controlled biofunctionalization and the reconstitution of relevant anatomical structures, such as fine-patterned liver sinusoids. Bioprinting will complement our high-throughput 3D microtissue methods with capabilities that allow to emulate vascularization, spatial organization of tissue microdomains, as well as immune cell patterning. Furthermore, by combining 3D bioprinting with live cell biosensors, we aspire to reveal human cell crosstalk at the single cell level within a physiological microenvironment.

Teaching

  • - At KI I am the Director of the Bioinformatics course within the International Master's Program in Translational Physiology and Pharmacology. In addition, I teach courses in local anaesthetics, cardiovascular pharmacology, pharmacokinetics and receptor pharmacology. - MSc projects are available upon request.

Articles

All other publications

Grants

Employments

  • Professor, Department of Physiology and Pharmacology, Karolinska Institutet, 2023-

Degrees and Education

  • Docent, Karolinska Institutet, 2018

News from KI

Events from KI