Human Immune Disorders Lab

Our research interests lie in the study of human diseases that affect the immune system. This includes immunodeficiency (defects in the functioning of the immune system), allergy (overactive immune system) and autoimmunity (immune system attacking the body). A large focus of ours has been primary immunodeficiencies – rare inborn errors of immunity caused by germline mutations in single genes that have crucial roles in the mammalian immune system. In this context, Associate Professor Cindy Ma’s lab investigates the role of the molecules encoded by these genes, and the pathways they involve in the development, differentiation and effector function of human lymphocytes. Our goal is to identify the molecular mechanism(s) underlying disease pathogenesis in these inborn errors of immunity, and to advance our understanding of the fundamental concepts required for a functioning human adaptive immune system. In doing so, we hope to reveal novel therapeutics in the treatment of these disorders.

Allergic diseases affect around one in three Australians, causing significant health and financial burdens. While the cellular basis of these diseases is known – such as pathogenic lymphocytes and activated B cells – researchers are yet to fully understand the mechanisms that lead to these pathogenic cells. Until the mechanisms underlying the pathogenesis of allergic diseases are identified, we will not be able to develop more effective treatments for these debilitating conditions.

Primary immunodeficiencies diseases (PIDs) result from damaging variants in genes that affect the development and function of immune cells. In addition to life-threatening infections, patients with PIDs often suffer from severe allergies. By investigating the immune cells of patients with PIDs and patients with allergies, our lab aims to discover the mechanisms of allergic diseases and develop novel approaches to understand and treat these conditions.

Some ongoing projects in the lab include:

1. Utilising PIDs as a genetically-defined human model to identify molecular, phenotypic and functional signatures that define human T helper 2 (Th2) cells – a type of lymphocyte that plays an important protective role in the immune system’s response to extracellular pathogens, but implicated in the pathogenesis of atopic diseases.
2. Harnessing single cell RNA-sequencing technologies to identify gene regulatory networks underpinning the aberrant generation of pathogenic Th2 and IgE-secreting B cells in atopic PID patients and patients with atopic disease.
3. Applying Next Generation Sequencing to patients with early-onset severe allergic disease due to an unknown genetic cause, to discover novel genes implicated in this condition.
4. Investigating immune cell changes in patients pre- and post-treatment with Dupilumab (a monoclonal antibody used to alleviate atopic disease by blocking the effects of the Th2 cytokines interleukin (IL-4 and IL-13).
5. Investigating other lymphocyte subsets implicated in atopic disease. This includes:

Overall, we hope to increase our understanding of the cellular mechanisms involved in allergic disease and identify opportunities to develop new therapies, providing a crucial and currently unmet need for effectively managing and treating it.