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
PhD student
PhD student
PhD student
With about 20 million infections each year, hepatitis E virus (HEV) represents a significant global health burden. Despite a growing awareness, the comprehension of this virus and its life cycle at the molecular level remains scarce. A contributing factor is the necessity to grow the virus in cell culture systems, which are usually based on aberrant cancer cells.
In order 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).
HEV is a positive-strand RNA, non-enveloped virus (nHEV), which gains a membranous host-derived envelope when budding from cells. In this form, the virus is called quasi-enveloped HEV (eHEV). While nHEV is ingested and shed into feces for fecal-oral transmission to another host, eHEV circulates in the blood of infected patients. The projects in our lab are geared towards studying the role of the quasi-envelope during different HEV life cycle steps, such as entry, innate immune sensing, assembly, secretion, in and from polarized cells (Figure 2). We further explore novel treatment options. Our studies are supported by a strong network of collaborations and state of the art technologies available on the outstanding campus environment of Heidelberg University.
Figure 2: HEV life cycle and transmission (adapted from Fu et al., 2019). (A) e/nHEV particles infect hepatocytes through their basolateral membrane. (B) Replication of the HEV genome (green) mediated by HEV nonstructural proteins occurs in a yet uncharacterized cellular compartment. (C) Subgenomic RNA is translated into ORF2 capsid protein (grey) and ORF3 protein (purple). The assembly site of infectious HEV particles is unknown. (D) Progeny HEV particles bud into multivesicular buddies mediated by the interaction of ORF3 with the ESCRT machinery of the host cell. (E) Basolaterally secreted eHEV particles are quasi-enveloped and circulate in this form in the bloodstream. The envelope protects eHEV particles from neutralizing anti-ORF2 Abs. (F) Apically secreted particles bud as eHEV particles and are then matured into nHEV particles. While exact modes of nHEV entry (A) are unknown, (G) eHEV particles enter through clathrin-dependent endocytosis. Cell-to-cell transmission or (H) transmission between neighboring apical domains has not been described yet.
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October 2024: Elif and Paula joined the lab as PhD students
September 2024: Huanting's paper is online
August 2024: Niclas Meier started his Master thesis in the lab
July 2024: Congrats to Charlotte on the brilliant defense of her thesis
March 2024: Brilliant oral presentation by Ann-Kathrin at the GfV meeting in Vienna
June 2023: With Rebecca and JunGen (and Clara) at the EASL in Vienna
January 2023: Patrick joined the lab as a PhD student
Sept 2022: Congrats to Jun-Gen for being accepted at the EASL Basic Science School: Precision Cut Liver Slices and Liver Organoids
July 2022: Zoé joined the lab as an MSc student
May 2022: Valentina joined the lab as an MSc 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