Michelle Clark - Infectious Diseases & Immune Defence division

Michelle Clark - Infectious Diseases & Immune Defence division

Start Time: 
Mon, 04/10/2021 - 3:00pm
End Time: 
Mon, 04/10/2021 - 4:00pm

WEHI PhD Completion Seminar hosted by Professor Marc Pellegrini


Michelle Clark

PhD Student - Pellegrini Laboratory

Infectious Diseases & Immune Defence division – Infection, Inflammation & Immunity Theme


‘Unleishing’ host cell death pathways to promote the clearance of HBV and Leishmania spp. infections


Join via TEAMS

Including Q&A session


Cell death plays a pivotal role in normal development, tissue homeostasis and immunity. It is the final defence an infected cell can provide to protect the multicellular organism from an invading pathogen. Unfortunately, it is also the target of successful chronic intracellular pathogens which halt cell death to complete their replication cycles. Two such infectious pathogens are the Hepatitis B Virus (HBV) and the Leishmania species of parasite. 


Hepatitis B is a chronic viral infection that if left untreated can cause liver cirrhosis and hepatocellular carcinoma. Currently over 220,000 Australians are living with chronic HBV. Current antiviral therapy successfully suppresses viral replication, however strict daily adherence is required to maintain suppression. This results in a significant personal burden for the patient. Even with strict adherence to therapy, patients still bear an increased risk of developing liver cancer. Therefore, therapeutics that provide a cure are still desperately needed. Previous work has shown that inducing extrinsic apoptotic cell death pathways may be an effective curative treatment for chronic HBV infection.  


Leishmania donovani is a unicellular parasite that causes the severe disease known as visceral leishmaniasis. This neglected tropical disease and can be difficult to treat as current therapies have severe side effects and resistance to therapeutics is spreading. If left untreated, visceral leishmaniasis has a greater than 95% mortality rate. Exploring cell death pathways and how they can be targeted therapeutically may provide new, safer therapies for treating leishmaniasis.  


Michelle’s PhD project aimed to further explore cell death pathways in both chronic HBV infection and leishmaniasis, and to determine whether these pathways could be therapeutically targeted to provide better treatments. Michelle was able to build on and support previous studies that suggest IAP inhibitors, which induce extrinsic apoptosis in infected cells, could provide a curative therapeutic for HBV. Michelle then investigated the interactions of Leishmania donovani with host cell death pathways, elucidating therapeutic targets that could further improve treatments for visceral leishmaniasis. 


All welcome!