Theme 3: Target Validation, Assay Development and Drug Screening & Theme 3.3: High throughput assays for specific viral targets: HBx-DDB1 & HBc-cccDNA

Professor Wanjin Hong
Executive Director, Institute of Molecular and Cell Biology (IMCB), A*STAR
Honorary Joint Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS

This Theme will focus on validation of previously discovered novel targets at the same time develop new assays against validated or putative targets that can be used for drug screening. Professor Wanjin Hong is the Theme PI for the LCG Theme 3 and 3.3.  Prof Hong’s role is to develop assays for high throughput screening for specific viral targets: HBx-DDB1 and HBc-cccDNA.

The Experimental Drug Development Centre (EDDC) will function as a collaborator at all levels of this theme, from target validation to drug discovery. Starting with early target proposals, EDDC will be able to provide insights regarding the attractiveness, as well as practicability of a target. address the ease of assay development for screening activities including assay validation using industry standards. In addition, we will provide information about the historical success for a given target of interest and extent this to guiding assay development and screening activities, as well as additional steps such as secondary assays, lead optimization activities, and suitable in vivo models. EDDC’s clinical development team will help to address general issues in terms of clinical viability of a project. This will also include hit and lead criteria commonly applied in the drug discovery process for small molecule compounds and based on input from EDDC’s biologists and chemists. We will give advice on which hits and leads should be pursued for further development, based in the attractiveness and patentability of the chemical scaffolds discovered. EDDC would provide advice on how to optimize the interaction of a potential agent with its putative target. EDDC will form an integrated project team comprising key representatives from all relevant parties.

 

 

 

Theme 3.1: To identify and chacterarize previously identified novel targets using proteomics & tool compounds as baits

Dr Tan Yee Joo
Associate Professor, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, NUS
Joint Senior Principal Investigator, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)

Yee Joo Tan is currently working at the Department of Microbiology and Immunology as well as IMCB as a joint appointee. Her laboratory focuses on molecular virology and uses various cell-based models to study different viruses including hepatitis B and C viruses. In the LCG program, she is a co-investigator under Theme 3. Working closely with Dr Jayantha Guyaratne and other LCG members, she has previously identified novel targets affected by HBV replication but the exact nature of the interaction between the virus and host proteins is unclear. In this LCG, identifying, characterizing and validating previously identified novel targets will be a goal.

 

 

 

Theme 3.2: To validate previously identified novel targets and transform into robust assays

Dr Giridharan Periyasamy
Head – High Throughput Phenomics, Experimental Drug Discovery Centre (EDDC)

Dr Giridharan, previously Platform leader at Centre for High Throughput Phenomics at Genome Institute of Singapore, is the head of High Throughput Phenomics at Experimental Drug Development (EDDC), A*STAR. His research interests consist of Drug resistance, Drug development, Cell signaling pathway(s) and combination studies. As a Co-Investigator in theme 3, his role will be to validate previously identified novel targets and transform them into robust assays.

 

 

 

Theme 3.4: Humanised mice for target validation and drug discovery

Dr Chen Qing Feng
Senior Principal Investigator, IMCB, A*STAR
Senior Principal Investigator, SIgN, A*STAR
Associate Professor, NUS

We have successfully established a human liver chimeric humanized mouse model where >70% mouse liver hepatocytes are replaced by human hepatocytes through the transplantation of human hepatocytes from normal donors into Fah-/-RAG22-/-IL2Rg-/- (FRG) immunodeficient mice. With the stable reconstitution of high levels of human hepatocytes, this model is able to support robust in vivo HBV infection and replication. Our task in LCG program is to focus on developing human liver chimeric humanized mouse models for drug testing and target validation. And also the optimization and application of personalized humanized mouse model for precision drug testing and target fishing.

 

 

 

Theme 3.5: Small molecule libraries for validated HBV Targets

Dr Lam Yulin
Associate Professor, Department of Chemistry, National University of Singapore

Despite the many agents approved for Chronic Hepatitis B treatment, none has been able to eradicate the virus. Thus, our role in this program is to design and synthesize new classes of lead compounds that would interact with new or existing targets as clinically efficacious anti-HBV drugs.

 

 

 

 

 

 

 

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