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Dao Thi Lab
We study hepatitis E virus-host interactions using stem cell-derived culture systems

ABOUT US

CIID building

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.

Uni klinikum
CHS foundation

WHO WE ARE

Loan
Viet Loan
Dao Thi, PhD

Principal Investigator

x Loan

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.

Andrew
Andrew
Freistaedter, MSc

Lab manager

x Andrew

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.

Rebecca
Rebecca
Fu, MSc

PhD student

x Rebecca

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.

Charlotte
Charlotte
Decker, MSc

PhD student

x Charlotte

Charlotte finished her Master’s degree in Molecular Biotechnology in Heidelberg. She is now working as a PhD student on hepatitis E virus trafficking.

In her leisure time she enjoys reading and swimming.

Ann-Kathrin
Ann-Kathrin
Mehnert, MSc

PhD student

x Ann-Kathrin

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.

Huanting
Huanting
Chi, MSc

PhD student

x Huanting

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-Gen
Jun-Gen
Hu, MSc

PhD student

x Jun-Gen

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.

Sarah
Sarah
Prallet

PhD student

x Sarah

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!"

Lars
Lars
Maurer

MD student

x Lars

Lars is a medical student at the University of Heidelberg. His MD thesis, supported by the SFB1129, is a collaboration between the Dao Thi lab and the Grimm lab. In his project Lars is exploring AAV-based expression of HEV capsid as a novel vaccine candidate.

In his free time, he enjoys going to the gym and meeting friends.

OUR WORK

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.

Our work is funded by generous grants from different sources

CHS foundation

DZIF
SFB1129
TRR179

OPEN POSITIONS

MD position available to conduct a medical doctoral thesis, with the project entitled "Hepatitis E virus interaction network to establish therapies"

We can only accept German medical students who are willing to spend 12-15 months in the lab. Please send your CV and motivation letter to VietLoan.DaoThi {at} med.uni-heidelberg.de

SELECTED PUBLICATIONS

    2021
  • Bovea 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 forDetecting 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

LAB NEWS


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

Jan 2020: Christmas dinner
Jan 2020: Christmas dinner

Nov 2019: Guglielmo started his internship in the lab


July 2019: Rebecca and Charlotte's review paper accepted at Viruses

June 2019: The lab participated in the BASF Firmencup race
June 2019: The lab participated in the BASF Firmencup race
June 2019: The lab participated in the BASF Firmencup race

May 2019: Lars started his MD thesis in the lab

Feb 2019: The lab attended the 1st Essen Hepatitis E meeting
Feb 2019: Cindy gave a talk at the 1st Essen Hepatitis E meeting

Feb 2019: First group photo


Feb 2019: Charlotte and Rebecca joined the lab as our first PhD students

Dec 2018: First Christmas dinner
Dec 2018: First Christmas dinner
Dec 2018: First Christmas dinner
Dec 2018: First Christmas dinner

CONTACT

Loan

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