Targeted deletion of disease-causing T cells

• PhD

T lymphocytes continually balance decisions between activation and tolerance that are critical for effective immunity and for preventing autoimmunity. These decisions require processing of multiple sources of signals. Antigenic stimulation of naive T cells initiates cell division and transition from the homeostatic survival programme to a new survival control mechanism. Using murine models, we identified that during this transition phase cells are vulnerable to cell death and elimination (Koenen Nat Comms 2013; Heinzel Nat Immunol 2017; Heinzel ICB 2023). This project aims to translate these findings to the human system to establish whether targeted inhibition of reprogramming pathways during antigenic stimulation of human T cells can be used for the specific deletion of disease-causing T cells to treat autoimmune diseases such as coeliac disease.

The Hodgkin lab studies the immune system with the goal of building conceptual computational models that can be used to improve vaccine development and treatments for autoimmunity and cancer. Experimental work focusses on the mechanics of how lymphocytes perceive and process multiple signals to regulate proliferation, survival and differentiation. The resulting theoretical solutions illustrate how we might simplify our understanding of cellular heterogeneity, the coding of complex behaviour and the stepwise transformation of healthy responses to various malignancies. The overall goal is to translate experimental insights to the building of functional models that can inform and improve our predictions for how the immune system will behave, how it leads to disease and how drug therapies can be optimally targeted to individuals.

Heinzel S 2024 Immunol Cell Biol 102(1): 46-57
Cheon H 2021. Frontiers in Bioinformatics 1(50): 723337.
Heinzel S 2017 Nat Immunol 18(1): 96-103.
Marchingo JM 2014 Science 346(6213): 1123-1127.
Koenen P 2013 Nat Commun 4: 1735.