Defining the mechanisms of thymic involution and regeneration

Defining the mechanisms of thymic involution and regeneration

Project details

The thymus is uniquely dedicated to the production of T cells. Curiously, the thymus undergoes age-related atrophy, referred thymic involution, which greatly diminishes T cell generation in adults. This limitation in T cell production can be life-threatening in patients receiving cyto-ablative therapies and/or haematopoietic stem/progenitor cell transplants. 

Compromised T cell reconstitution renders these patients highly susceptible to infection; therefore strategies to rejuvenate thymic function are necessary. We have discovered novel features of thymic involution and regeneration that may be amenable to therapeutic intervention. In this project, we will apply new single-cell and imaging technologies to better define the mechanisms underpinning thymic involution and new strategies to restore T cell lymphopoiesis. 

Microscope view of cells

About our research group

Our laboratory investigates how the molecular control of cell death processes shape immune cell homeostasis, function and malignancy. We have a long-standing interest in the thymus, in particular how the epithelial cells of this organ orchestrate T cell differentiation.  

Our recent discoveries have uncovered key cellular and molecular processes in thymic epithelium essential to thymic function and adaptive immunity. We seek to build on these and other discoveries to define new strategies to reverse thymic atrophy and restore T cell immunity in immunodeficient patients.

Key technologies used in the team include advanced flow and mass cytometry (CyTOF), lightsheet and intravital microscopy, in vivo models of disease, experiments with human material and bioinformatic analysis of complex sequencing and single-cell data.

Background literature includes: Heinlein et al., Science Immunology 2022 7(67):eabb6032; Jain et al., Cell Death & Differentiation 2021 28(10):2946; Jain et al., Blood 2017 130(23):2504; Gray et al, Blood 2007 108(12):3777. 

 

Email supervisors

 

Researchers:

Associate Professor Daniel Gray

Associate Professor Daniel Gray
Associate Professor
Daniel
Gray
Joint Division Head

Project Type: