Aikaterini Evgenia (Katie) Miari
PhD Student
department-of-biology
In 2019 I successfully completed my undergraduate degree at Glasgow Caledonian University (GCU) in Cell & Molecular Biology. During my undergraduate degree I was awarded a Wellcome Trust Biomedical Vacation Studentship (June-July 2018, GCU), in the lab of Dr Fiona Kerr. I then completed my Honours Project in the lab of Professor Ann Graham, focusing on inflammatory signalling in cardiovascular disease (academic year 2018-2019).
I began my PhD at GCU in October 2019 in the lab of Dr Mark Williams. My studies focus on Acute Myeloid Leukaemia (AML), one of the most common blood cancers in adults in the UK. Conventional chemotherapy regimens are unfortunately not successful, leading to high relapse and mortality rates in patients. Despite the development of new targeted therapies, patient outcomes have yet to improve and resistance continues to develop. As AML arises in the bone marrow, my research focuses on uncovering mechanisms by which cell-to-cell contacts and the environmental conditions within the bone marrow may contribute to therapy resistance.
Specifically, our lab is interested in uncovering the role of fibroblasts in AML within the hypoxic niche of the bone marrow. Cell-to-cell interactions between fibroblasts and leukaemia cells, as well as secreted factors released by the fibroblasts, have previously been shown to protect the leukaemia cells against the effects of therapy, mainly by induction of pro-survival/anti-apoptotic signalling. In collaboration with our academic contacts (Dr Helen Wheadon, Paul O’Gorman Leukaemia Research Centre; Dr Monica Guzman, Weill Cornell Medical College) we have developed a unique, three-dimensional cell culture system to assess fibroblast-AML cell interactions in a low-oxygen environment, allowing to more accurately model cell-to-cell interactions within the bone marrow. Pathways of interest to this project include pro-survival/anti-apoptotic signalling via MAPK, STAT3, SK1 and MCL-1.
Our lab is also interested in understanding the role of immune cells in AML, in particular macrophages, as we are now beginning to understand the importance of these cells in patient outcomes. Using the same three-dimensional model system, primary monocyte-derived macrophages will be co-cultured with leukaemia cells to investigate resistance mechanisms.
With our work, we hope to uncover signalling events underlying therapy resistance within the bone marrow and identify targets that can be targeted by the development of novel therapeutics or by the use of existing therapies via drug repurposing.