John Rizk

PhD project by John Rizk

Name: John Rizk
Project Title: Transcriptional and post-translational control of T lymphocytes
Group: T cell signaling and development
Supervisor: Vasileios Bekiaris
Co-Supervisors:William Agace

Project Description:

T cells are one of the most important cells of the human immune system. Their natural function is to help the body fight invading microbes. However, they can also cause autoimmune diseases when they are out of control. The body has many different types of T cells, each with specific functions. Two types of T cells are particularly important to fight big bacteria and fungi. They are called Th17 cells and γδT17 (gamma delta T 17) cells. Both cell types make a protein called interleukin (IL)-17 that is important for protection against bacteria but is also involved in diseases such as multiple sclerosis and arthritis. Therefore, it is important to understand how these cells are regulated and how can the production of IL-17 be manipulated. This thesis investigated multiple mechanisms that have the potential to regulate the functions of those T cells using experimental wet-lab techniques, disease models and next generation analysis of all the proteins and genes in the cells.

Results from this study shows that using a class of pharmacological compounds called Smac mimetics (SM), the production of IL-17 by both mouse and human T cells can be reduced. Treatment with SM showed beneficial effects in pre-clinical disease model of multiple sclerosis. It also shows an important novel role for two proteins called cIAP1 and cIAP2 in controlling the functions of T cells that produce IL-17. Additionally, the role that two very similar proteins, called STAT5A and STAT5B, play in regulating such gamma delta T 17 cells was described for the first time. Indeed, when the IL-17 producing cells lacked both STAT5A and STAT5B there was complete resistance to multiple sclerosis like symptoms in the pre-clinical model.

These results could open the door for the development of new therapeutics that could target these proteins (cIAP1, cIAP2, STAT5A or STAT5B) in various diseases including rheumatoid arthritis and multiple sclerosis. For instance, the SM compounds are already in clinical trials for cancers and their potential uses could thus be expanded to include autoimmune diseases. Also, there is a great interest in developing pharmacological agents that could specific target STAT5 proteins for various diseases.

Kontakt

John Atef Micheal Baky Rizk
Gæst
DTU Sundhedsteknologi

Kontakt

Vasileios Bekiaris
Gruppeleder, Lektor
DTU Sundhedsteknologi
35 88 68 28

Kontakt

William Winston Agace
Gruppeleder, Professor
DTU Sundhedsteknologi
35 88 68 99