WEHI PhD Completion Seminar hosted by Dr Vanessa Bryant

Dr Samantha Chan

PhD Student – Bryant Laboratory, Immunology division – Infection, Inflammation & Immunity Theme, WEHI

Untangling Genetic and Extrinsic Influences on T Cell Dysregulation: Insights from Inborn Errors of NFKB1 and CMV Infection

 

Davis Auditorium

Join via TEAMS

Including Q&A session

Followed by refreshments in Tapestry Lounge

Advances in next-generation sequencing have greatly improved our ability to identify the genetic causes of primary immunodeficiencies (PIDs). However, translating these genomic findings into clinically actionable strategies remains a challenge. One major obstacle is the significant phenotypic variability within gene defects and mutations, which complicates predictions about patient outcomes. Variants of uncertain significance are also increasingly common. These issues are particularly prominent in adult immunodeficiency; affected patients accumulate decades of infections, comorbidities, and treatment-related complications that obscure the genetic and environmental factors influencing immune dysregulation.

My research focuses on these challenges, particularly in the context of Cytomegalovirus (CMV) infection in Common Variable Immunodeficiency (CVID). My research has revealed strong associations between CMV infection, inflammatory complications of CVID, and inborn errors of the NF-κB signalling pathway. Despite the clinical significance of these factors, the relationship between them is poorly understood due to their complex interplay. To address this, I developed model systems of genetically engineered T cells to investigate the role of NF-κB signalling in T cell effector responses and determine whether this has the potential to contribute to the immune dysregulation observed in patients with NFKB1-related primary immunodeficiency. This approach not only enhances our understanding of PID pathogenesis, but also offers a powerful platform for developing personalised diagnostic and treatment strategies, adaptable to various patient-specific mutations, associated genes, and environmental influences on immune health.

Dr Samantha Chan (MBBS, BMedSci, MPH, FRACP) is the Deputy Director of the Clinical Immunology and Allergy Department at the Royal Melbourne Hospital and an Honorary Clinical Fellow in the Department of Medicine at the University of Melbourne. She leads both investigator-initiated and commercial clinical trials in immunodeficiency, including a gene therapy study for hereditary angioedema.

All welcome!