Matthew graduated in Immunology from Brown University, USA, in 2012. He then obtained his PhD at Duke University, USA in 2018, where he studied the effector functions of antibodies against HIV-1. He continued his work as a postdoctoral fellow at the Singapore Immunology Network (SIgN), A*STAR, where he continued research work on antibodies, malaria, and subsequently SARS-CoV-2. In 2020, he moved from SIgN to the newly founded A*STAR Infectious Diseases Labs (A*STAR ID Labs).
Antibodies are an important component of immune protection against infectious disease. Our research investigates the antimicrobial functions of antibodies, for instance virus neutralization. Evaluating antibodies for these antimicrobial functions helps optimize the effectiveness of antibody-based diagnostics and therapeutics against current and emerging pathogens. For each antibody, we also relate its antimicrobial functions to its mode of interaction with its target, including its interaction structure and binding epitope. Such studies identify the epitopes targeted for protective immunity, which provides leads into which epitope targets are important to include for an effective vaccine.
Antimicrobial function-based identification of antibodies
Pathogens express surface antigens that can be targeted by antibodies. Most antibody discovery approaches utilize recombinant soluble versions of these antigens, and sift for antibody candidates that can bind well to them. However, empirical data has shown that the best binders are not necessarily the most effective antibodies. We are developing a microfluidic process capable of identifying antibodies based directly on their antimicrobial functions, such as virus neutralization or bacterial opsonophagocytosis. This will broaden the spectrum of effective antibodies developed against a given pathogen target, which may increase the overall effectiveness of antibody candidates. Furthermore, this process can uncover novel antigens or epitopes on the pathogen that are effectively targeted by protective antibodies. Such novel epitopes represent potential vaccine candidates. We are currently using this approach against Chikungunya virus, a vector-borne disease which regularly causes outbreaks that infect thousands to millions of people globally.
Pandemic preparedness and response
Antibodies can be developed rapidly for both diagnostic and therapeutic use against emergent infectious diseases, as has been prominently demonstrated in the global response to the COVID-19 pandemic. Our ongoing studies include investigation into the functions of antibodies against immunodominant linear epitopes of SARS-CoV-2. These studies will inform SARS-CoV-2 vaccine development and evaluation. Future work for pandemic preparedness includes the generation of a suite of reporter cells and pseudovirus vectors that can be used for rapid identification of functional antibodies against new pandemic threats. Notably, this approach circumvents the use of a soluble recombinant antigen. This saves valuable time and increases our response speed since it is often difficult to synthesize such an antigen accurately.
Antibody mechanisms against multi-drug resistant pathogens
Antimicrobial resistance is a major emerging threat – a 2019 UN report indicated that drug-resistant diseases already cause 700,000 deaths globally a year, a figure that could increase to 10 million deaths per year by 2050, surpassing cancer to be the top killer globally, if no action is taken. Antibodies are well suited to overcome antimicrobial resistance due to the diversity of their modes of binding and antimicrobial action. Our research aims to discover the binding modes and mechanisms of effective antibody action against common multi-drug resistant pathogens, notably the ESKAPE pathogens. This will facilitate the development of effective antibodies that may be used as adjunct therapies against multi-drug resistant pathogens.
Full publication list can be found on Google Scholar.
More information on Matthew’s laboratory - http://www.antimicrobialbiologicslaboratory.com
|Postdocs (PhD)||Research Officers ||PhD/Undergraduate Students |
| Kian Ping CHAN||Yuling HUANG|
| Nicholas LIN||Ajayanandan YADUNANDAN|
| ||Sooriya SELVAM|| |