Dr Theodoros Simakou
- Research Assistant (Immunology & Infection)
I am interested in the field of immunology and mechanobiology. My research primarily focuses on understanding the roles of the mechanosensory channel PIEZO1 in the differentiation and phenotypes of macrophages and other cells that make up the joint. The joints are highly dynamic and mechanical, and the cells which reside in their tissues are exposed to a plethora of physical stimuli. Such physical stimuli occur physiologically in healthy tissues and are altered during pathologies.
The cells have evolved mechanisms to sense and respond to mechanical forces, through a process known as mechanotransduction. PIEZO1 is a professional mechanosensor involved in such process, and I have researched its roles in immune cells since 2017, starting from my PhD and continuing in my current postdoctoral position. Synovial tissue resident macrophages are of particular interest for mechanobiology, due to their arrangement in epithelial-like barriers, and their exposure to forces originating from synovial fluid and cell-to-cell interactions with each other and fibroblasts. Other macrophages derived from monocytes, are equally sensitive to a wide variety of in-tissue mechanical forces, which can affect their phenotypes and activation.
On the medical aspects of research, understanding the role of mechanotransduction in synovial macrophages, can unravel mechanisms that are involved in initiation of inflammation and autoimmunity in joints. Targeting these mechanisms could lead to development of new therapeutics for diseases such as Rheumatoid Arthritis.
In my research I utilise my experience in the field of cell and molecular biology to study the effects of PIEZO1 activation on synovium tissue resident macrophages. My scientific and methodological approach utilises advanced culture techniques for ex vivo work such as 2D and 3D cocultures, histological assessments, induced Pluripotent Stem Cell cultures, CRISPR-Cas9 for gene knockout and knock-in in primary cells, flow cytometry and cell sorting, and single-cell transcriptomics for unbiased analysis. The experimental observations are then tested in animal models, for confirming them in in vivo conditions.
In addition to research, I am also committed to teaching and supervision of undergraduate and postgraduate immunology students.
Figure 1: F-actin cytoskeleton and cell morphology after PIEZO1 activation in iPSC-derived macrophages, which resemble the embryonal-derived tissue resident macrophages (B), compared to vehicle control (A)
Other projects in the lab
Grants and Awards listed are those received whilst working with the University of Glasgow.
- BSI Career Enhancing Grant
British Society for Immunology
2023 - 2024
- Marcus Doohan 2439044D@student.gla.ac.uk