Our group studies Lymph Node Stromal Cells (LNSCs) and their interactions with leukocytes in the context of clinically relevant diseases and disease models. We are looking into their interactions with the leukocytes that promote autoimmunity, inflammatory shock, and cancer, examining both basic immunobiology and therapeutic angles. We focus closely on fibroblastic reticular cells (FRCs) and their ability to control inflammatory responses. We are based at Monash University at the Biomedicine Discovery Institute in the Department of Biochemistry and Molecular Biology, but the views expressed on this site are our own, and this site is not maintained nor endorsed by Monash University.
The immunology of FRCs has become a hot topic in the past ten years due to their far-reaching influence on T cells, B cells and dendritic cells. FRCs are typically found in lymph nodes where they form a 3D mesh upon which immune cells travel along communicating with each other. They are essentially the “highway” for immune cells, and to some extent the traffic warden as well, as they secrete molecules that direct the cells to the appropriate spaces within the lymph node and instruct the immune cells to ignore certain molecules that are a natural part of the body. A lot of autoimmune diseases are caused by immune cells that disregard such instructions and attack the body’s own molecules.
We were among the first to routinely isolate and characterise these cells and we have used them in mouse models to show that they are highly effective against septic shock (Fletcher et. al. 2014). We are investigating their potential as a cell therapy candidate.
Our recent studies focus on their role in the human immune system and we are establishing their mode of action and identifying effective ways to control their operation. We have a number of projects that look into their interactions with different immune cells. We have established collaborations with academia and industry and are working on bringing these cells to the clinic in the future.
One of our research projects is establishing the role of cancer-associated fibroblasts (CAFs) in solid tumours. We have projects studying these cells in the context of breast, colon and pancreatic cancer. Specifically, we are intrigued by their mechanisms of action on other immune cells.
We are interested in the role of FRCs in T cell proliferation, activation and differentiation. We have recently discovered mechanisms of action in the human setting and are actively pursuing ways and developing assays to control these mechanisms.
One project that has been in development is looking into the role of FRCs in monocyte maturation and differentiation.
We are developing assays to test NK cell interaction with both FRCs and CAFs. Our early data is promising and seems to support the idea that NK cells are affected by these cells types.