Research

 

Main Research Interest

Our main research interest is Natural Killer cell (NK cell) biology and function. Interleukin 15 (IL-15) is a potent stimulator of NK cell activation and proliferation, and as a result, is an important focus in our laboratory. Classically, NK cells are known for their role in fighting viral infection and cancer, and many studies examine their roles within this context. What makes NK cells truly fascinating is their role not only as an effector, but also as a key and early player in the first line of defense against infection in their ability to directly recognize pathogens. NK cells are important for the early immune response against pathogens and play a role in danger recognition. These cells can be directly activated in response to Toll-like receptor (TLR) ligands as shown to the left in the images of NK cells taken by confocal microscopy. Here, human NK cells stimulated with a TLR ligand, FimH, are shown to be activated as evidenced by translocation of transcription factor NF-κB to the nucleus.

 


NK Cell Cancer Immunotherapy

A major goal of our research program is to find a better and safer treatment for cancers, particularly for those for which we have no or very limited treatment options. Our natural immune system protects us from growth of cancerous cells. One of the most important innate cell types responsible for natural defense against cancer cells is the natural killer (NK) cell.  Read more... 

 

Innate Immunity and Infection


Herpes Simplex Virus-2 Infection

The innate immune system is a critical component in combating infection. It provides a quick initial immune response to bacterial or viral challenges and shapes and stimulates the adaptive immune response that is ultimately responsible for clearing the infection. As the repertoire of cells and cytokines in the innate immune environment is vast and diverse, a few areas have become prominent research focal points within our lab.

Interleukin-15:

We are currently investigating the signalling pathway of IL-15 and its effects on the innate immune environment during viral infection. While it is well-known that IL-15 signals through lymphocytes through a trans-presentation mechanism, in which IL-15 is presented by IL-15 receptor-α to the IL-2β and common-γ-chain receptors on lymphocytes, a different mechanism of IL-15 signalling and activation may be occurring in immune cells of myeloid lineage. As a widely expressed cytokine with a crucial impact during infection, research that focuses on understanding IL-15 will have fundamental impacts on health and human disease. Read more...


Hepatitis C Infection


Hepatitis C is caused by the hepatitis C virus (HCV), a positive-sense single-stranded RNA virus of the Flaviviridae family. Usually transmitted through contact with infected blood, HCV infection presents as a global health problem. With ~3% of the world population currently infected, of these cases, 70~80% eventually develop chronic disease with a risk for liver fibrosis and cancer. Although it is not clear why, some individuals can spontaneously clear HCV while others establish lifelong chronic infections. The rate of spontaneous clearance of HCV significantly varies among different ethnicities. Read more...

 

Humanized Mouse Model - An Experimental Model of Human Disease

Although mouse models have provided extremely valuable insights into basic physiology and pathology of human cells, tissues and organs, there are situations where they may not represent human defense/susceptibility against microbial pathogens and cancers. Studies of human cells, including human NK cells, and their interactions with human specific pathogens or cancer cells have largely been restricted to in vitro experiments and the lack of appropriate in vivo models has been a major impediment.  Recent advances in the generation of humanized mice have provided a valuable means of assessing the interaction of human cells with human pathogens or cancer cells in an in vivo setting.

We and others have developed this relevant pre-clinical humanized mouse model and our goal is to use this model to develop novel prevention and/or therapeutic strategies against human diseases.

 

 

 

 

Double Humanized Mouse Model for the Study of Hepatitis C Infection

Using FRG mice that have been reconstituted with human liver cells and autologous immune cells, we have generated an autologous double humanized mouse model. These mice have both a functional human immune system and human liver cells that can be infected wtih HCV to study HCV immunopathogenesis.  

 

 

Our research is supported by: