Our Research
Research Interests
Tissue resident macrophages are evolutionary old, tissue-resident myeloid cells, found from invertebrates (e.g. D. melanogaster) to higher mammals (e.g. Homo sapiens). They are phagocytic cells and are generally characterised as tissue sentinels against invading pathogens. Yet, macrophages are far more than just bug-eaters! They actually have important roles in tissue homeostasis. We are generally interested to understand the functions of macrophages at steady state and in disease and how they regulate tissue homeostasis.
Elie Metchnikoff first described phagocytes (i.e. macrophages) more than a century ago in the star fish larvae as cells that fight against invading pathogens and as regulators of tissue homeostasis. Much later, van Furth proposed the term “mononuclear phagocyte system” (MPS), according to which mononuclear phagocytes in the blood (i.e. monocytes) give rise to tissue-resident phagocytes (i.e. macrophages). In the past decade, advances in the study of myeloid cells have demonstrated that the majority of tissue-resident macrophages (e.g. microglia, Kupffer cells) develop during embryogenesis. Although, the development of tissue-resident macrophages has been extensively studied, their in situ functions are unclear and need to be better defined. In our endeavour to understand the role of macrophages within a specific tissue, we seek to answer simple, yet, important, questions: Who? What? When? Where? Why? How? Answering these fundamental questions will help us shed some light on the fascinating world of macrophages!
Research Methods
We employ a plethora of research techniques to study macrophages e.g. flow cytometry and gene expression. Since it is impossible to understand the biology of macrophages within their native tissue using cell lines or in vitro techniques, we rely heavily on in vivo models. We mainly use murine gentic tools (e.g. knock-in/out mice, constitutive and inducuble gene manipulation, reporter and fate-mapping models) to target and study tissue-resident macrophages. Importantly, we strongly believe that appropriate localisation of cell populations within their natural tissue setting is critical for relating cell diversity to function. Therefore, in order to answers our scientific questions, we are very keen on state of the art imaging techniques: e.g. immunofluorescence (IF) microscopy, whole mount with tissue clearing, intravital microscopy, and transmission electron microscopy (TEM). If you are interested to see some representative pics and videos of our work, do have a look at our gallery!
Research Projects
A) The role of myeloid cells in immune complex-driven nephritis
Immune complexes (IC)-mediated pathologies (also known as type III hypersensitivity reactions) affect millions worldwide, with a very high socioeconomic burden. Type III hypersensitivity frequently targets the kidney, causing inflammation, which could progress to end stage renal failure and the need for dialysis or transplantation. The current therapeutic interventions for IC-mediated nephritis are costly, non-specific and come with severe side effects. A better understanding of the mechanistic underpinnings of the disease is needed, in order to build new, more specific treatments.
Myeloid cell infiltration is one of the most striking features of renal inflammation caused by IC and it correlates with poor patient prognosis. Our published work has shown that the macrophages that reside in the renal interstitium, termed kidney-resident macrophages (krMΦs), initiate type III hypersensitivity in the kidney, by scavenging circulating IC that are pumped into the renal interstitium by endothelial cells.
Our findings provide a simple model to explain how IC cause kidney inflammation. Yet, despite this progress, the underlying mechanisms that lead to IC-mediated tissue injury remain unclear. We aim to delineate the role of different subsets of myeloid cells in IC-driven inflammation in the kidney. Thus, our work has the potential to discover novel pathways that can be further harnessed for the prevention of type III hypersensitivity.
B) Elucidating the function of kidney-resident macrophages (krMΦs) in kidney infection(s)
The innate immune response to renal infections (namely monocytes and neutrophils) has been extensively studied. Surprising, the role of kidney-resident macrophages has not been adequately addressed, although they are in an ideal position to detect, respond and orchestrate the immune response to the infectious agent(s). Our published work has recently shown that the macrophages that reside in the renal interstitium, termed kidney-resident macrophages (krMΦs), initiate an inflammatory reaction in response to a local danger signal (in the form of immune complexes). Our results highlight krMΦs as sentinels of the renal interstitium. Yet, studies so far have failed to identify their role in the pathogenesis of renal infections. We seek to delineate the role of krMΦs in bacterial, viral or fungal infections invasive in the kidney, to discover novel pathways that can be further harnessed for the prevention and/or treatment of patients.
