Research

04 May 2018

Recognition of double-stranded RNA and regulation of interferon pathway by toll-like receptor 10

Suki Lee, principal investigator at HKU-Pasteur Research Pole, and her colleagues at HKU School of Biomedical Sciences and Chinese Academy of Sciences have recently revealed a novel nucleotide sensing receptor and provides new mechanistic insight explaining its role in regulating IFN response in an article for Frontiers in Immunology.

Toll-like receptor (TLR)-10 is the least characterized TLR and still remains an orphan receptor, with only very limited information available regarding its localization, agonist, signaling and function. We have revealed lately that TLR10 is predominantly localized to endosomes and binds dsRNA. We provided different lines of evidences to demonstrate that dsRNA is in fact a ligand for TLR10 sensing and signaling, thereby identifying a previously unrecognized role of TLR10 as a novel nucleotide sensing receptor. We also revealed that TLR10 competes with TLR3 for ligand binding and proposed a model to illustrate the mechanisms for dual functions of TLR10 in the regulation of dsRNA-mediated IFN signaling. This work provides new mechanistic insight explaining the major role of TLR10 in regulating IFN response upon dsRNA stimulation.

As there is increasing evidence suggesting the involvement of TLR10 in different disease pathogenesis. We believe that these new findings not only provide important fundamental insights to the understanding of immunobiology of TLR10, but also bring indispensable importance to further investigate the role and functional relevance of TLR10 in diseases. Modulation of TLR10 signaling may thus provide a unique option to fine-tune fundamental physiological pathways involved in disease pathological conditions.

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12 Apr 2018

[SCHEDULE CHANGE] Dr Yan Li from Institut Pasteur Paris is invited to talk on Evaluation and development of immunotherapies with humanized mouse models

HKU-Pasteur Reseach Pole is pleased to invite Yan Li in Hong Kong for a seminar in April on Evaluation and development of immunotherapies with humanized mouse models. Dr Yan Li is currently a postdoc in Institut Pasteur Paris in Prof. James Di Santo's laboratory, he is an expert in developing humanized mouse models. 

Evaluation and development of immunotherapies with humanized mouse models

Date: Tuesday, 17 April 2018

Time: 11:00

Venue: Room 7-03, 7^th Floor, HKJC Building for IR, 5 Sassoon Road, Pokfulam

Abstract: In recent decades, advances in our understanding of autoimmunity and cancer immunity dramatically improved immunotherapies against these diseases. Interestingly, effective antitumor immunity exploits the same mechanism underlying autoimmunity, whereas knowledge acquired from tumor immunotherapy can be applied to treat autoimmune diseases.  To evaluate and develop novel immunotherapies, we developed models of human tumor and autoimmune diseases from human immune system (HIS) mice. In this talk, I will demonstrate the potential of HIS mice for biological drug discovery and as a preclinical platform to assess the efficacy and toxicity of immunotherapies.

Biosketch: Dr. Yan LI obtained his Ph.D from Singapore-MIT alliance program under the supervision of MIT Professor Jianzhu CHEN. He then moved to the Institut Pasteur in Paris where he is currently a postdoc in Prof. James DI SANTO’s laboratory. Dr. Li has over 10 years’ experience of developing humanized mouse models.

ALL ARE WELCOME!

28 Mar 2018

On the track of a universal Influenza vaccine: feedbacks on the latest trends

Sophie Valkenburg, principal investigator at HKU-Pasteur, and her colleagues from the Peter Doherty Institute for Infection and Immunity and the department of Infectious Diseases, St. Jude Children’s Research Hospital in Memphis publish a comprehensive review on the hope provided by the next-generation Influenza vaccines relying on T cells.

Sophie Valkenburg, HKU-Pasteur Research Pole

Using T cells to improve the limitations of current Influenza vaccines is definitely promising. However, before achieving a universal Influenza vaccine that harness the power of these immune cells, a myriad of questions remain to be addressed: which T cells are needed to fight the infection, and how, when and where to use this cells to unleash their therapeutic potential?

Find out more in the review published in Vaccines, a MDPI open-acces journal.

Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine
E. Bridie Clemens, Carolien van de Sandt, Sook San Wong, Linda M. Wakim and Sophie A. Valkenburg
Vaccines 2018, 6(2), 18; doi:10.3390/vaccines6020018
 

20 Mar 2018

Is MERS-CoV a threat for Africa?

The Middle Respiratory Syndrom coronavirus (MERS-CoV) is a virus circulating in dromaderies, a common animal of the Arabian Pensinsula and also found in great numbers in many countries of the African continent. The virus has crossed from dromaderies to humans in the Arabian Peninsula, but this hasn't been observed in any African countries (imported and nosocomial infections only). Why?

Malik Peiris, co-director of HKU-Pasteur Research Pole and his colleagues united in a large international collaboration tackle this issue. In PNAS, they report the first evidences of genetic and phenotypic differences between the viruses of the 2 geographical areas, contributing to answer the question.

The viral respiratory disease was first identified in humans in 2012, in Saudi Arabia. Since then, more than 2,100 people have been infected with MERS-CoV, of whom 813 have died. WHO classifies the virus as one of the 10 priority emerging diseases given its potential to cause a public health emergency and the absence of efficient treatments or vaccines.

© CIRAD, S. Cognet

Learn more about the publication in the press release from CIRAD, the French centre for agricultural and development research involved in the study.

You can also read our story "MERS on the radar at HKU-Pasteur Research Pole" that comes back to 3 years of research on the coronavirus, or read Malik's interview on the occasion of his election to the US National Academy of Sciences.

The publication:

MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity
Chu DKW, Hui KPY, Perera RAPM, Miguel E, Niemeyer D, Zhao J, Channappanavar R, Dudas G, Oladipo JO, Traoré A, Fassi-Fihri O, Ali A, Demissié GF, Muth D, Chan MCW, Nicholls JM, Meyerholz DK, Kuranga SA, Mamo G, Zhou Z, So RTY, Hemida MG, Webby RJ, Roger F, Rambaut A, Poon LLM, Perlman S, Drosten C, Chevalier V, Peiris M.
Proc Natl Acad Sci U S A. 2018 Mar 5. pii: 201718769. doi: 10.1073/pnas.1718769115.

08 Mar 2018

Where to look for novel therapeutical targets against Flaviviruses?

Read Tami Zhang, Iolanthe Lan and Sumana Sanyal review in Frontiers in Microbiology, "Modulation of Lipid Droplet Metabolism - A Potential Target for Therapeutic Intervention in Flaviviridae Infections“ available for all to read online. 

Abstract: 
Lipid droplets (LDs) are endoplasmic reticulum (ER)-related dynamic organelles that store and regulate fatty acids and neutral lipids. They play a central role in cellular energy storage, lipid metabolism and cellular homeostasis. It has become evident that viruses have co-evolved in order to exploit host lipid metabolic pathways.
This is especially characteristic of the Flaviviridae family, including hepatitis C virus (HCV) and several flaviviruses. Devoid of an appropriate lipid biosynthetic machinery of their own, these single-strand positive-sense RNA viruses can induce dramatic changes in host metabolic pathways to establish a favorable environment for viral multiplication and acquire essential components to facilitate their assembly and traffic.
Here we have reviewed the current knowledge on the intracellular life cycle of those from the Flaviviridae family, with particular emphasis on HCV and dengue virus (DENV), and their association with the biosynthesis and metabolism of LDs, with the aim to identify potential antiviral targets for development of novel therapeutic interventions.

Keywords: lipid droplet, lipid metabolism, HCV, flavivirus, dengue

The publication is available here.

22 Feb 2018

[Seminar] In vitro models of Hepatitis B and Ebola viruses replication: Applications for drug discovery

HKU-Pasteur Research Pole invites Marc Windisch in Hong Kong for a seminar on in vitro models of Hepatitis B and Ebola viruses replication in February. Marc Windisch is a professor from the Institut Pasteur Korea (IPK) where he as established the Applied Molecular Virology Laboratory dedicated to drug discovery and early drug devlopment, we are pleased to welcomes him for this seminar: 

In vitro models of Hepatitis B and Ebola viruses replication: Applications for drug discovery

Date: Tuesday, 27 February 2018

Time: 16:30

Venue: Room 7-03, 7th Floor, HKJC Building for IR, 5 Sassoon Road, Pokfulam

Biosketch:

Dr. Windisch received his Master- and Ph.D. degrees at the Center for Molecular Biology Heidelberg and at the Medical University of Heidelberg in Germany working on hepatitis B- and hepatitis C viruses (HBV & HCV), respectively. Since 2007, he is Principal Investigator at the Institut Pasteur Korea (IPK), a translational research organization, where he has established the Applied Molecular Virology Laboratory dedicated to drug discovery and early drug development. In 2018, Marc became acting Executive Director of the Discovery Biology Division at IPK overseeing RnD efforts of 7 teams. In his function as Viral Drug Discovery Project Leader, Marc developed a pre-clinical drug candidate with a novel mechanism of action for chronic HCV which was licensed out. In addition, he devised strategies for cell-based, phenotypic, target-free high content/throughput screening (HCS/HTS) campaigns to identify drugs and/or novel host targets for HIV, HCV, Dengue, HBV, Zika, Ebola, MERS-CoV, and hepatitis E virus. Furthermore, in collaboration with international and local companies, he conducted HTS campaigns and structure-activity relationship studies.  Since 2016, Dr. Windisch is Professor at the University of Science & Technology in Korea at the Department of Chemical Biology guiding Master and Ph.D. students, investigating the spread of HBV in vitro, the transmission of the virus from cell-to-cell, the involvement of lipids in viral entry, etc. Marc has interest in RnD of viral interventions (small molecule, peptide, antibody, RNAi), innate immunity, lipids, disinfectants, and he has a start-up mindset.

Contact: marc.windisch@ip-korea.org

ALL ARE WELCOME