Predictive Biomarker Panels to Specific Anti-Myeloma Therapeutics
Since the emergence of high-throughput proteomic techniques and advances in clinical technologies, there has been a steady rise in the number of cancer-associated diagnostic, prognostic, and predictive biomarkers being identified and translated into clinical use. The characterisation of biofluids has become a core objective for many proteomic researchers in order to detect disease-associated protein biomarkers in a minimally invasive manner. In our lab we aim to develop predictive biomarker panels to specific anti-myeloma therapeutics by analysing the proteomes of various biofluids including blood plasma, serum, saliva and extracellular vesicles with the ultimate goal of aiding myeloma diagnosis, prognosis and to monitor therapeutic response and minimal residual disease.
Clinical Collaborators:
Prof. Peter O’Gorman (MMUH, Ireland)
Dr. Theodora Vatopoulou (St. George’s University Hospital, UK)
Academic Collaborators:
Dr. Paul Dowling (Maynooth University, Kildare, Ireland)
Prof. Margaret McGee (School of Biomolecular and Biomedical Sciences, UCD, Ireland)
Biobank:
Blood Cancer Biobank Ireland (MMUH, Dublin, Ireland)
Finnish Haematology Registry and Clinical Biobank (FHRB Biobank, Finland)
Decoding Extramedullary Multiple Myeloma (EMD)
EMD represents an aggressive form of Multiple Myeloma, characterised by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment. EMD can present in the liver, skin, central nervous system, pleura, kidneys, lymph nodes and pancreas and is present in 6-8% of newly diagnosed MM cases and 10-30% of relapsed MM patients. EMD is considered high risk and is associated with poor prognosis with a median overall survival of less than 6 months. Currently there are no official guidelines regarding EMD clinical treatment and the survival outcomes for myeloma patients with EMD remain poor. We use Multi-Omics (genomics, transcriptomics, proteomics) and cell biology (cell culture, mouse models of disease, 3D tissue mimetic models) to understand how extramedullary myeloma develops in order to design molecular therapeutic strategies to tackle aggressive EMD.
Clinical Collaborators:
Prof. Peter O’Gorman (MMUH, Ireland)
Academic Collaborators:
Dr. Colm Ryan (School of Medicine, UCD, Ireland)
Dr. Paul Dowling (Maynooth University, Kildare, Ireland)
Prof. Margaret McGee (School of Biomolecular and Biomedical Sciences, UCD, Ireland)
Biobank:
Blood Cancer Biobank Ireland (MMUH, Dublin, Ireland)
Finnish Haematology Registry and Clinical Biobank (FHRB Biobank, Finland)
Tumour-Platelet Interactions in Multiple Myeloma (MM)
While the main role of blood platelets lies in haemostasis and thrombosis, platelets also play a pivotal role in a number of other pathological conditions. Platelets are the less-explored components from the tumour microenvironment in MM. Although some studies have recently revealed that MM cells have the ability to activate platelets even in the premalignant stage, this phenomenon has not been widely investigated in MM. Moreover, thrombocytopenia, along with bleeding, is commonly observed in those patients. We aim to understand the haemostatic disturbances observed in MM patients as well as the dynamic interactions between platelets and myeloma cells, with the view of implementing platelets for diagnostic and therapeutic purposes.
Academic Collaborators:
Prof. Maria-Jose Santos Martinez (School of Pharmacy and Pharmaceutical Sciences, TCD, Ireland)
Prof. Carlos Medina (School of Pharmacy and Pharmaceutical Sciences, TCD, Ireland)
Mitochondrial Dysfunction in Acute Myeloid Leukemia (AML)
AML is the second most common form of leukaemia in adults, and accounts for approximately 1% of new cancer diagnoses. The majority of patients, following intensive chemotherapy, achieve complete remission; however, AML remains a highly fatal disease, with a disheartening five-year survival rate of ~24%. The high fatality of this disease is attributed to the presence of primary resistance in a subset of patients and a high relapse rate with therapy-resistant disease following complete remission. Patients with an “adverse” chemoresistance risk present with impaired mitochondrial metabolism, including production of reactive oxygen species (ROS) and fatty acid oxidation. In our lab we aim to understand the relationship between dysregulated metabolism and cytarabine/daunorubicin chemoresistance in AML, with the ultimate goal to develop novel anti-AML therapies that will improve the survival of AML patients.
Academic Collaborators:
Dr. Katrina Lappin (Patrick G Johnston Centre for Cancer Research, QUB, Northern Ireland)
