Research

The general theme that unites the studies in our laboratory is Molecular Viral-Host Interactions. We have a special interest in enveloped virus entry and budding mechanisms, with an increasing focus on viruses that cause Emerging Infectious Diseases. We study highly pathogenic viruses, and use the Henipavirus as primary model systems to represent the pathogenesis of acute and chronic viruses, respectively.

  • Acutely pathogenic viruses, by definition, strongly subvert the host’s Innate immunity, and thus propagate and transmit themselves before the host’s adaptive immune system can come into play.
  • Chronic viruses that persist in the host result in “smouldering” infections. They can actively replicate in the host over long periods of time, and have evolved mechanisms to counteract or evade both the innate and adaptive immune systems.

Henipavirus is a new genus of paramyxovirus discovered around the turn of the 20th century. Nipah (NiV) and Hendra (HeV) virus are zoonotic viruses–transmitted to humans from their natural bat reservoir–that cause fatal encephalitis in 40-75% of infected patients. In many cases, the estimated time from infection to death is less than 2 weeks, with symptomatic periods lasting for 4-7 days.

How viruses survive, proliferate and transmit within and between hosts is a testament to the past and present evolutionary battles between host and pathogen. The guiding objective of our research is to obtain and translate basic knowledge about viral entry and replication processes to therapeutic or interventional anti-viral strategies. We are particularly interested in developing novel methods, reagents, and therapeutics to address long-standing and intractable problems in our fields of interest. For example, a recent focus of our lab is developing broad-spectrum antiviral strategies that target either viral or host cell components that are essential for multiple classes of virus.

EphrinB2 is the primary high affinity receptor that mediates NiV and HeV entry. EphrinB2 belong to a class of highly conserved receptor tyrosine kinases (RTKs) that are involved in germ layer differentiation, tissue boundary formation, and other critical developmental processes such as angiogenesis, neurogenesis and axonal guidance. The unique properties associated with NiV Env interactions with its entry receptor (EphrinB2), and the fortuitous property of EphrinB2 being expressed in highly relevant populations of various stem cells, has also resulted in exciting collaborations with stem cell biologists and gene therapists to exploit this high affinity interaction for therapeutic and interrogative purposes.