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Volker Lauschke

Researcher

Associate Professor in Personalized Medicine and Drug Development, Director of Biofabrication and Tissue Engineering Facility (Biofab), CEO HepaPredict AB

About me

Volker M. Lauschke (V.M.L.) is Associate Professor and group leader in Personalized Medicine and Drug Development (since 2017) at Karolinska Institutet (KI), Stockholm, Sweden and Director of the Micro- and Nanoengineering Facility at KI (since 2018).

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 100 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 and the AAPS High Impact Award 2020. 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 2018: Associate Professor in Personalized Medicine and Drug Development (Karolinska Institutet, Stockholm, Sweden)

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

2017 - 2018: Assistant Professor in Liver Function and Regeneration (Karolinska Institutet, Stockholm, Sweden)

2014 - 2016: Postdoctoral Research Associate and MarieCurie Fellow (Karolinska Institutet, Stockholm, Sweden)

2013 – 2014: Bridging Postdoctoral Research Associate (EMBL Heidelberg, Germany)

2007 – 2009: Scientific Assistant in Molecular Genomics and Evolution (University of Heidelberg, Germany)

Research description

Current group members

Sonia Youhanna (Postdoctoral Researcher)

Shane Wright (Postdoctoral Researcher)

Reza Zandi Shafagh (Postdoctoral Research Engineer)

Julianna Kele Olovsson (Senior Researcher)

Yitian Zhou (PhD Student)

Nuria Oliva-Vilarnau (PhD Student)

Joanne Shen (PhD Student)

Lena Preiss (PhD Student)

Aurino Kemas (PhD Student)

Jibbe Keulen (PhD Student)

Carolina Dagli Hernandez (Visiting PhD Student)

Stefania Koutsilieri (Visiting PhD Student)

Despoina-Christina Sismanoglou (Erasmus Student)

 

Selection of current projects

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.

 

Integrated microfluidic models for studies of complex diseases.

Type 2 diabetes mellitus (T2DM) affects 435 million patients globally and is characterized by insulin resistance of muscle, liver and adipocyte tissue in combination with progressive failure of pancreatic β‑cells, together resulting in loss of glycemic control. Due to the complexity of interactions between cells and tissues that are involved in the maintenance of human metabolic homeostasis, there is a lack of experimental tools to study T2DM. Pharmacologic therapy only allows for the management of T2DM and its sequelae and no cure is currently available, at least in part due to the lack of physiologically relevant and high-throughput compatible model systems.

We develop microfluidic chips using innovative polymers in which we can co-culture tissue models with relevance for T2DM. Specifically, we integrate human microphysiological and long-term stable 3D tissue models of liver, pancreas, adipose tissue and skeletal muscle and utilize this platform to investigate T2DM biology and to screen for novel anti-diabetic medications.

 

Development of hepatic disease models for drug discovery.

Non-alcoholic fatty liver disease (NAFLD) constitutes a clinicopathological condition that accounts for the majority of chronic liver disease cases in the Western world. Onset of NAFLD is hallmarked by the accumulation of lipids within hepatocytes (hepatic steatosis), which arises from an imbalance between triglyceride import, production and extrusion primarily caused by obesity and a hypercaloric diet. In some patients steatosis can progress to non-alcoholic steatohepatitis (NASH), an inflammatory condition that can further develop in liver fibrosis. Despite its significant importance, no pathophysiologically replicative model systems exist. Based on our 3D primary human hepatocyte spheroid model, we develop and extensively characterize novel in vitro platforms that are suitable to model human NASH and fibrosis.

 

Hepatic spheroids as model system for liver regeneration.

Strikingly, during spheroid aggregation stages, PHH first dedifferentiate, followed by rapid redifferentiation, providing an ideal ex vivo experimental paradigm to study the full spectrum of differentiation state changes that occur in vivo during liver regeneration. Besides extending our mechanistic understanding, this finding opened possibilities for the development of therapeutic approaches as a substitute for orthotopic liver transplantations. To this end, we work on the establishment of protocols in which PHH isolated from patients proliferate and, after cells sufficiently multiplied, are induced to redifferentiate into functional hepatocytes using our 3D spheroid culture system. We recently showed that miRNAs are important driving forces in the hepatic dedifferentiation process; knowledge which, besides being of mechanistic importance, can be useful for the optimization of hepatic redifferentiation.

 

Evaluation of the importance of rare genetic variants on hepatic metabolism and drug response.

Genetic variants primarily in drug and metabolite transporters, phase I and phase II drug metabolizing enzymes and nuclear receptors can influence drug response by modulating drug absorption, distribution, metabolism and excretion (ADME). Importantly, while in the past decades an ever-growing arsenal of genetic variants with demonstrated impacts on human drug response has been identified in these pharmacogenes, a substantial fraction of the heritable variability in drug response remains unexplained. Rare genetic variants that only occur in very few individuals and are hence missed in genome-wide association studies have been proposed to contribute to this missing heritability. We integrate data from recent population-wide Next-Generation Sequencing (NGS) projects to quantify the extent of genetic variability in pharmacogenes on a population level and, using an arsenal of in silico techniques, quantify the impact on hepatic metabolism and pharmacokinetics and -dynamics.

Teaching portfolio

  • At KI I teach courses in local anaesthetics, cardiovascular pharmacology, pharmacokinetics and receptor pharmacology.
  • MSc projects are available upon request.

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)

Academic honours, awards and prizes

Current and recent funding

ERC Synergy grant SPHERES, IMI2 EUbOPEN, VR 3R grant disease modeling, VR Starting grant, Rolf Luft Grant in Diabetes Research, SFO Stem Cells and Regenerative Medicine, Lennart Philipson Research Grant, VR 3R grant hepatotoxicity, Jeannson Grant.

We furthermore acknowledge support from Merck KGaA, Eli Lilly and Company and the Robert Bosch Foundation.

 

Fellowships, Prizes and Awards

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

 

Editorial Activities

Editor or Editorial Board Member: Frontiers in Pharmacology (Since 2017), Human Genomics (Since 2017), Frontiers in Medicine (Since 2018), Drug Metabolism Reviews (Since 2019), Current Drug Metabolism (Since 2019), Computational & Structural Biotechnology Journal (Since 2020), Current Research in Pharmacology and Drug Discovery (Since 2020), Pharmacogenomics Research and Personalized Medicine (Since 2020), Precision Cancer Medicine (Since 2020), The Pharmacogenomics Journal (Since 2020)

Senior Editor: Annals of Human Genetics (Since 2019)

Guest Editor of Special Issues in 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)

 

 

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