Volker Lauschke

Om mig

After studying Molecular and Cellular Biology at the University Heidelberg, Germany and the University of Bergen, Norway, I obtained my Ph.D. from the EMBL and the Combined Faculty of Natural Sciences and Mathematics of the University of Heidelberg for work on primary cell culture development and tissue patterning based on phase-encoding using molecular oscillators.

In 2014, I moved to Karolinska Institutet as a MarieCurie fellow to work on the development and characterization of physiological hepatic model systems and became Group Leader in Personalized Medicine and Drug Development in 2017.

My research group uses 3D cell culture systems of primary human cells, microfluidics and integrative bioinformatics approaches to identify novel therapeutic strategies for complex metabolic diseases, such as non-alcoholic fatty liver disease and type 2 diabetes. In addition, we develop algorithms to improve personalized pharmacological therapy and establish novel methods for the prediction of drug toxicity.

We put major emphasize on the dissemination of our discoveries in order to make innovations available to the public. To this end, we founded HepaPredict AB (www.hepapredict.com) a contract research organization (CRO) that got admitted into Karolinska Innovations DRIVE program. We offer in-house evaluations of drug metabolism, pharmacokinetic properties and safety as well as various liver disease models for drug discovery based on our novel long-term stable microphysiological 3D spheroid culture platform.

 

Professional Experience

Since 2018: Associate Professor in Personalized Medicine and Drug Development (Karolinska Institutet, Stockholm, Sweden)

Since 2018: Director of the Micro- and Nanofabrication Core Facility

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)

Forskningsbeskrivning

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.

Pedagogiska meriter

At KI I teach courses in local anaesthetics, cardiovascular pharmacology, pharmacokinetics and receptor pharmacology.

 

MSc projects are available upon request.

 

Utbildning

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)

Akademiska priser och utmärkelser

2017                Lennart Philipson Prize

2016                VR Starting Grant

2016                VR 3R Grant

2016                KI Fonder Grant

2016                VR Proof-of-concept Grant (Co-applicant)

2016                KI Early Verification Grant

2015                Lars Hierta Research Grant

2015                Sigurd och Elsa Goljes Minne Research Grant

2015                Eva och Oscar Ahréns Grant for Medical Research

2014                Marie Curie Fellowship

2013                Dedicated Research Highlight article in Nature Reviews Genetics

2013                Dedicated News and Views article in Nature

2009                EMBL International PhD Program Graduate Fellowship

2009                Top Master of Science (M.Sc.) Award

2006                Erasmus Fellowship