We are an international team of scientists who enjoy studying viruses. We use stem cell-derived culture systems to study hepatitis E virus-host interactions.
Our lab is a part of the Center of Integrative Infectious Disease Research (CIID) at the Heidelberg University Hospital. Our research is generously supported by the Chica and Heinz Schaller Foundation.
Principal Investigator
Lab manager
PhD student
PhD student
PhD student
PhD student
PhD student
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MD student
The Dao Thi lab uses stem cell-derived culture models to study hepatitis E virus (HEV). With about 20 million infections each year, leading to more than 3 million symptomatic cases and ~60'000 fatalities, HEV is believed to be the most common cause of acute hepatitis in the world. Despite increasing awareness, HEV remains an understudied virus. A contributor to the poor understanding is the difficulty to propagate HEV in cell culture. To overcome these limitations, we use embryonic or induced pluripotent stem cell (hESC/iPSC)-derived cell culture models, in particular stem-cell derived hepatocyte-like cells (HLCs; Figure 1).
Figure 1: Differentiation of human pluripotent stem cells (embryonic or induced, hESC/iPSCs) to hepatocyte-like cells (HLCs; Wu & Dao Thi et al. 2018, Gastroenterology).
Unlike conventionally used hepatoma cells, we found that HLCs are permissive for infection by primary isolates of all four HEV genotypes that can infect humans. HLCs therefore enable studies of authentic pan-genotype HEV biology. Further, the capability to study replication of non-adapted HEV isolates in tandem with autologous, patient-derived iPSCs enables personalized models of HEV infection and will serve as a platform for testing novel anti-HEV treatments (Figure 2).
Figure 2: Stem cell culture models of HEV infection. Cells collected from identified HEV positive individuals can be reprogrammed to generate iPSCs. Relevant SNPs can be repaired or introduced into established hESC/iPSC lines using CRISPR-Cas9, followed by differentiation to the cell type of interest. Differentiated cells can be directly infected with HEV isolates from patients or animals for modeling virus-host interactions in a dish (Dao Thi et al., 2018, Cold Spring Harb Perspect Med).
We also developed a novel stem cell-based differentiation protocol that uses transwell filters to generate columnar polarized HLCs. HEV is transmitted via the fecal-oral route and hepatocytes are similar to other epithelial cells polarized in vivo. In the absence of robust hepatocyte polarity systems our polarized HLC system now allows us to study directional HEV assembly and release, the final steps of the virus life cycle. Our efforts should lead to a better understanding of HEV life cycle and host interactions with the overriding goal of developing new specific antiviral treatments.
Post-doc position available to study determinants of tissue and species tropism of HEV.
For details please refer to the job ad.
Feb 2022: Jana joined the lab as an MD student
Jan 2022: Lars' paper is online
Oct 2021: Cindy's paper is online
Sept 2021: Sarah joined the lab as a PhD student
June 2021: Ann-Kathrin and Guglielmo's book chapter is online
Feb 2021: Jun-Gen joined the lab as a PhD student
Nov 2020: Huanting joined the lab as a PhD student
July 2020: Our contributions to overcome SARS CoV2 diagnostic shortages are online in Sci Trans Med and Viruses
April 2020: Ann-Kathrin joined the lab as a PhD student
April 2020: Our paper in Nature Communications is online
Feb 2020: Linh started her Master thesis in the lab
Nov 2019: Guglielmo started his internship in the lab
July 2019: Rebecca and Charlotte's review paper accepted at Viruses
May 2019: Lars started his MD thesis in the lab
Feb 2019: First group photo
Feb 2019: Charlotte and Rebecca joined the lab as our first PhD students
Viet Loan Dao Thi, PhD Junior Group Leader
Center for Integrative Infectious Disease Research (CIID) University Hospital Heidelberg Im Neuenheimer Feld 344 D-69120 Heidelberg, Germany
+49 (0) 6221 563 56 43
VietLoan.DaoThi {at} med.uni-heidelberg.de