Mechanisms of thymic regeneration

• PhD

The thymus is the only organ that makes T cells. Yet, despite its importance, the thymus is the first organ in the body to undergo age-related atrophy, termed involution.

Thymic involution greatly reduces the output of new naïve T cells and is linked to poor immune function in the aged. It is a particularly big problem following myeloablation for haematopoietic stem/progenitor cell transplantation (HSCT).

The thymus is also a regenerative organ. We recently discovered a unique feature of thymic involution that blocks certain regenerative processes.

This project will use mouse genetic models, advanced imaging, spectral flow cytometry and human samples to define the mechanisms of thymic regeneration that can overcome involution and restore T cell function in the aged.

Many mechanisms have evolved to ensure that the immune system does not attack our own tissues; a property referred to as immunological tolerance.

The main goal of our team is to understand how to modify tolerance mechanisms to create new ways to treat cancer and autoimmune diseases.

The genesis of immune tolerance is in the thymus where various stromal cells orchestrate the process of T cell differentiation and selection. Defects in this process underlie many autoimmune conditions and immunodeficiencies.

We seek to better understand thymic function to create new strategies to overcome immunodeficiencies.

Background work includes:
Kousa, Jahn, Zhao, et al Nature Immunology 2024; Sep;25(9):1593-1606.
Heinlein, et al., Science Immunology 2022 Jan 21;7(67):eabb6032
Jain, et al., Blood 2017, Dec 7;130(23):2504-2515.”