Associate Professor in Personalized Medicine and Drug Development, Director of Biofabrication and Tissue Engineering Facility (Biofab), CEO HepaPredict AB
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.
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)
Current group members
Sonia Youhanna (Postdoctoral Researcher)
Shane Wright (Postdoctoral Researcher)
Reza Zandi Shafagh (Postdoctoral Research Engineer)
Julianna Kele Olovsson (Senior Researcher)
Qingyang Xiao (PhD Student)
Yitian Zhou (PhD Student)
Nuria Oliva-Vilarnau (PhD Student)
Joanne Shen (PhD Student)
Lena Schaller (PhD Student)
Aurino Kemas (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.
- At KI I teach courses in local anaesthetics, cardiovascular pharmacology, pharmacokinetics and receptor pharmacology.
- MSc projects are available upon request.
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 (2020-2025)
IMI2 EUbOPEN (2020-2022)
VR 3R grant disease modeling (2019-2021)
VR Starting grant (2016-2020)
Rolf Luft Grant in Diabetes Research (2017-2020)
SFO Stem Cells and Regenerative Medicine (2020)
Lennart Philipson Research Grant (2017-2019)
VR 3R grant hepatotoxicity (2016-2019)
VR Proof-of-concept Grant (2017)
Jeannson Grant (2017)
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
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)