Dao Thi Lab

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ABOUT US

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.

More about our work

WHO WE ARE

Viet LoanDao Thi, PhD

Principal Investigator

About

After completing her dual studies in Biotechnology at the Technische Universität Berlin (Germany) and Dongseo University in Busan (South Korea), Loan received her PhD from the École Normale Supérieure in Lyon (France) where she trained with Prof. François-Loïc Cosset. She then pursued her interest in virology during two complementary postdoctoral phases in the labs of Prof. Darius Moradpour at the Centre Hospitalier Universitaire Vaudois in Lausanne (Switzerland) and Prof. Charles M. Rice at the Rockefeller University in New York (USA).

In 2018, Loan returned to Germany to join the Virology department at Heidelberg University Hospital as a Chica and Heinz Schaller Junior Research Group Leader.

When not doing science, Loan likes to travel and hike.

AndrewFreistaedter, MSc

Lab manager

About

Andrew grew up in "The South" of the U.S., getting his Master's degree in North Carolina. As of 2017, he has been living in Germany, getting a feel for the European lifestyle.

RebeccaFu, MSc

PhD student

About

Rebecca is from Canada and did her BSc in Biotechnology at the University of British Columbia in Vancouver. She then did her MSc Infectious Diseases at University of Edinburgh in Scotland and worked during her Master thesis on Herpes Simplex Virus-1 viral entry. After the MSc, she worked as a research assistant at University of Edinburgh and did research on HIV-1 restriction factors.

Since February 2018, Rebecca joined the lab for her PhD studies on HEV host interactions.

Outside the lab she enjoys baking, reading, hiking and going to the gym.

Ann-KathrinMehnert, MSc

PhD student

About

Ann-Kathrin obtained a BSc in Molecular Biotechnology and completed her MSc in Molecular Biosciences/Infectious Diseases at Heidelberg University. During her Master thesis, she worked on establishing genetic tools in the malaria parasite Plasmodium knowlesi.

In April 2020, she joined the group as a PhD student to investigate the innate immune response in HEV-infected hepatocytes, supported by TRR179.

Outside the lab, Ann-Kathrin enjoys cycling, reading and drinking good coffee with friends.

HuantingChi, MSc

PhD student

About

Huanting received her BSc degree in Medicine from Soochow University in China. Then she completed her MSc program in Reproductive Sciences at the University of Edinburgh in Scotland. Huanting joined our lab in November 2020 for her PhD studies on the immunotherapy of chronic HEV infection, supported by the DZIF.

In her free time, Huanting likes hiking and playing badminton.

Jun-GenHu, MSc

PhD student

About

Jun-Gen received his Bachelor and Master degrees in biology from Sichuan University, China. Jun-Gen joined the lab in February 2021 for his PhD studying HEV protein trafficking in liver ECM-based PSC-HLCs culture systems. His stay is supported by the China Scholarship Council.

Outside the lab he enjoys cooking, biking, hiking and photography.

SarahPrallet

PhD student

About

After her BSc studies in Biology, Biochemistry, and Biotechnologies in Lyon, Sarah completed her first year of MSc in Infectiology at Université Paris Diderot and her second year MSc in Molecular and Cellular Biology at the Université Paris Sorbonne. After her Master studies, she worked for almost 2 years at Fab’entech, a French biotech company.

Sarah joined the Dao Thi lab in September 2021 to study the innate immune response in HEV-infected intestinal cells.

She is passionate about mountains and outdoor sport, such as climbing, running, alpinism, and skiing. My state of mind is: "Where there is a will, there is a way. Passion is the fuel behind every successful career!"

PatrickBröscky

PhD student

About

Patrick obtained his bachelor degree from the TU Darmstadt in microbiology. He obtained his master degree from the TU Darmstadt/MPI in Marburg and the LMU in Munich in bacteriology. For his PhD, he transitioned to virology and joined our lab in January 2023. Generously funded by SFB1129, he will investigate the trafficking of the HEV ORF3 protein in polarized cells.

Outside of the lab he enjoys reading, going to the gym and too many other hobbies.

PaulaJordan, MSc

PhD student

About

Paula obtained her Bachelor's and Master's degree in Biomedical Sciences in Marburg where she studied the Nipah Virus. In October 2024 she joined our lab for her PhD studies on the HEV life cycle.

Outside of the lab she enjoys photography, cooking and going to the gym.

ElifToprak, MSc

PhD student

About

Elif received her BSc degree in Molecular Biology and Genetics from Bilkent University, Ankara. She then completed her Master's degree in Developmental, Neural and Behavioral Biology in Göttingen, Germany, focusing her thesis work on neural differentiation of iPSCs. In October 2024, she joined Dao Thi's lab to work on HEV tropism and innate immune response with co-cultures of iPSC-derived immune and hepatocyte-like cells.

Outside the lab, she loves to take long walks in the forest, cuddle with her cat, and take up new hobbies from time to time.

OUR WORK

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.

Project examples for further details:

Hepatitis E virus trafficking in polarized human pluripotent stem cell-derived hepatocyte-like systems
Impact of the enteric stage of hepatitis A virus and hepatitis E virus on the outcome of liver infection

Our work is funded by generous grants from different sources

OPEN POSITIONS

Please check back later for future opportunities.

SELECTED PUBLICATIONS

2024

Chi H, Qu B, Prawira A, Richardt T, Maurer L, Fu R, Lempp FA, Zhang Z, Grimm D, Wu X, Urban S, Dao Thi VL (2024). An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes. EMBO Rep. 25(10):4311-4336 Pubmed
Klöhn M, Burkard T, Janzen J, Haase JA, Gömer A, Fu R, Ssebyatika G, Nocke MK, Brown RJP, Krey T, Dao Thi VL, Kinast V, Brüggemann Y, Todt D, Steinmann E. (2024). Targeting cellular cathepsins inhibits hepatitis E virus entry. Hepatology 80(5):1239-1251 Pubmed

2023

Csernalabics B, Marinescu MS, Maurer L, Kelsch L, Werner J, Baumann K, Zoldan K, Panning M, Reuken P, Bruns T, Bengsch B, Neumann-Haefelin C, Hofmann M, Thimme R, Dao Thi VL, Boettler T. (2023). Efficient formation and maintenance of humoral and CD4 T-cell immunity targeting the viral capsid in acute-resolving hepatitis E infection. J Hepatol. 80(4):564-575 Pubmed
Schrader JA, Burkard TL, Brüggemann Y, Goemer A, Meister TL, Fu R, Mehnert AK, Dao Thi VL, Behrendt P, Durantel D, Broering R, Vondran FWR, Todt D, Kinast V, Steinmann E. (2023). EGF receptor modulates HEV entry in human hepatocytes. Hepatology. 77(6):2104-2117 Pubmed

2022

Maurer L, El Andari J, Rapti K, Spreyer L, Steinmann E, Grimm D, Dao Thi VL (2022). Induction of Hepatitis E virus anti-ORF3 antibodies from systemic administration of a muscle-specific adeno-associated virus (AAV) vector. Viruses 14(2), 266 Viruses

2021

Zhang C, Freistaedter A, Schmelas C, Gunkel M, Dao Thi VL, Grimm D (2021). An RNA interference/adeno-associated virus vector-based combinatorial gene therapy approach against Hepatitis E virus. Hepatol Commun. 6(4):878-888 Pubmed
Bove G, Mehnert A-K, Dao Thi VL (2021). Chapter 7, iPSCs for modeling hepatotropic pathogen infections, Editor: Alexander Birbrair, In Advances in Stem Cell Biology, iPSCs for Studying Infectious Diseases, Academic Press, Volume 8, p. 149-213. Science Direct
Herbst K, Meurer M, Kirrmaier D, Anders S, Knop M, Dao Thi VL (2021). Colorimetric RT-LAMP and LAMP-sequencing for Detecting SARS-CoV-2 RNA in Clinical Samples. Bio Protoc. 11(6):e3964 Bio Protoc

2020

Dao Thi VL, Herbst K, Boerner K, Meurer M, Kremer LPM, Kirrmaier D, Freistaedter A, Papagiannidis D, Galmozzi C, Stanifer ML, Boulant S, Klein S, Chlanda P, Khalid D, Miranda IB, Schnitzler P, Kräusslich H-G, Knop M, Anders S (2020). A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples. Science Translational Medicine. 12:eabc7075 Sci Trans Med
Klein S, Müller TG, Khalid D, Sonntag-Buck V, Heuser A-M, Glass B, Meurer M, Morales I, Schillak A, Freistaedter A, Ambiel I, Winter SL, Zimmermann L, Naumoska T, Bubeck F, Kirrmaier D, Ullrich S, Barreto Miranda I, Anders S, Grimm D, Schnitzler P, Knop M, Kräusslich H-G, Dao Thi VL, Börner K, Chlanda P (2020). SARS-CoV-2 RNA Extraction Using Magnetic Beads for Rapid Large-Scale Testing by RT-qPCR and RT-LAMP. Viruses. 12:863 Viruses
Dao Thi VL, Wu X, Belote RL, Andreo U, Takacs CN, Fernandez JP, Vale-Silva LA, Prallet S, Decker CC, Fu RM, Qu B, Uryu K, Molina H, Saeed M, Steinmann E, Urban S, Singaraja RR, Schneider WM, Simon SM, Rice CM (2020). Stem cell-derived polarized hepatocytes. Nature communications. 11:1677 Nat Comm

2019

Fu RM, Decker CC, Dao Thi VL (2019). Cell Culture Models for Hepatitis E Virus. Viruses. 11:608 Viruses
Wang J,Qu B,Zhang F,Zhang C, Deng W, Dao Thi VL, Xia Y (2019). Stem Cell-Derived Hepatocyte-Like Cells as Model for Viral Hepatitis Research. Stem Cells International. 2019:9605252 Stem Cells International

2018

Dao Thi VL, Wu X, Rice CM (2018). Stem cell-derived culture models of hepatitis E virus infection. Cold Spring Harbor Perspectives in Medicine. a031799 Pubmed
Wu X*, Dao Thi VL*, Liu P, Takacs CN, Xiang K, Andrus L, Gouttenoire J, Moradpour D, Rice CM (2018). Pan-Genotype Hepatitis E Virus Replication in Stem Cell-Derived Hepatocellular Systems. Gastroenterology. 154:663-674 Pubmed
Todt D, Moeller N, Praditya D, Kinast V, Friesland M, Engelmann M, Verhoye L, Sayed IM, Behrendt P, Dao Thi VL et al. (2018). The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo. Antiviral Research. 157:151-158 Pubmed
Knegendorf L, Drave SA, Dao Thi VL, Debing Y, Brown RJP, Vondran FWR, Resner K, Friesland M, Khera T, Engelmann M et al. (2018). Hepatitis E virus replication and interferon responses in human placental cells. Hepatology Communications. 2:173-187 Pubmed
Wu X, Dao Thi VL, Huang Y, Billerbeck E, Saha D, Hoffmann H-H, Wang Y, Vale Silva LA, Sarbanes S, Sun T et al. (2018). Intrinsic immunity shapes viral resistance of stem cells. Cell. 172:423-438 Pubmed
Chung H, Calis JJA, Wu X, Sun T, Yu Y, Sarbanes SL, Dao Thi VL, Shilvock AR, Hoffmann HH, Rosenberg BR et al. (2018). Human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell. 172:811-824 Pubmed

Earlier papers

Takacs CN, Andreo U, Dao Thi VL, Wu X, Gleason CE, Itano MS, Spitz-Becker GS, Belote RL, Hedin BR, Scull MA et al. (2017). Differential regulation of lipoprotein and hepatitis C virus secretion by Rab1b. Cell Reports. 21:431-441 Pubmed
Dao Thi VL, Debing Y, Wu X, Rice CM, Neyts J, Moradpour D, Gouttenoire J (2016). Sofosbuvir inhibits hepatitis E virus replication in vitro and results in an additive effect when combined with ribavirin. Gastroenterology. 150:82-85 Pubmed
Hiroz P, Gouttenoire J, Dao Thi VL, Doerig C, Moradpour D, Sahli R, Telenti A (2013). Mise à jour sur l’hépatite E. Revue Médicale Suisse. 9:1594-1598 Journal website
Molina-Jimenez F, Benedicto I, Dao Thi VL Gondar V, Lavillette D, Marin JJ, Briz O, Moreno-Otero R, Aldabe R, Baumert TF, Cosset FL, Lopez-Cabrera M, Majano PL (2012). Matrigel-embedded 3D culture of Huh-7 cells as a hepatocyte-like polarized system to study hepatitis C virus cycle. Virology. 425:31-39 Pubmed