Dr Jim Vadolas

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoietic stem cells that predominantly affect older adults. The disease is characterised by ineffective blood cell production, chronic inflammation within the bone marrow, persistent cytopenias, and an increased risk of progression to acute myeloid leukaemia (AML).

Because MDS typically develops gradually and persists for many years, it can significantly affect quality of life. Many patients experience ongoing fatigue, recurrent infections, and progressive functional decline due to low blood cell counts and a significant impact on quality of life when regular blood transfusions are required. These challenges, together with the limited availability of disease-modifying treatments, have led to strong engagement from patients and carers who advocate for earlier recognition of the biological processes that drive disease progression.

Clinically, MDS is broadly divided into lower-risk (LR-MDS) and higher-risk (HR-MDS) categories. LR-MDS represents the majority of cases and usually follows a relatively indolent course, although patients often experience persistent anaemia or other cytopenias. In contrast, HR-MDS is associated with higher blast counts, greater genomic instability, and a substantially increased risk of transformation to AML, an aggressive form of blood cancer.

Despite decades of research, there is still no universally effective therapy that can reliably alter the natural history of MDS or prevent progression to leukaemia. Increasing evidence indicates that aberrant innate immune signalling and chronic inflammation play central roles in driving disease development and progression.

Our research aims to better understand how inflammatory processes influence the evolution of MDS. By integrating inflammatory profiling with molecular and genomic data, we seek to identify inflammatory signatures that predict progression from early or pre-MDS states to LR-MDS, HR-MDS, and ultimately AML. These insights will help improve risk stratification and may enable earlier, more targeted therapeutic intervention for patients with inflammation-driven disease trajectories.

Multiple Myeloma (MM) is a clonal plasma cell malignancy that predominantly affects older adults. Despite substantial advances in therapy, including proteasome inhibitors, immunomodulatory agents, monoclonal antibodies, and cellular therapies, MM remains largely incurable. Most patients eventually relapse following an initial therapeutic response, driven by pronounced genetic heterogeneity, clonal evolution, and adaptive resistance within the bone marrow microenvironment. As survival improves, MM increasingly manifests as a chronic condition characterised by increased morbidity rather than durable remission.

Importantly, MM behaves not only as a malignancy but as a systemic, multisystem disorder. Malignant plasma cells disrupt the bone marrow niche, impairing normal haematopoiesis and leading to anaemia, immunodeficiency, and infection susceptibility. These factors collectively contribute to frailty, reduced quality of life, and increased mortality in the elderly. While current risk stratification rely heavily on cytogenetic abnormalities and cancer burden, it does not adequately capture inflammatory or microenvironmental drivers of disease severity and progression. As a result, prognostication remains incomplete, and treatment is often insufficiently personalised.

Identifying robust prognostic biomarkers of inflammation in MM represents a major opportunity to improve patient outcomes. Such biomarkers could provide mechanistic insight into disease trajectory, enable more precise risk stratification beyond genetic lesions alone, and inform personalised treatment strategies.

Thalassaemia and sickle cell disease are inherited blood disorders that affect haemoglobin, the protein in red blood cells responsible for transporting oxygen throughout the body. Together, they represent some of the most common genetic diseases worldwide and affect millions of people, particularly in regions of Africa, the Mediterranean, the Middle East, and Asia.

Thalassaemia results from mutations that reduce the production of α- or β-globin chains, key components of haemoglobin. This imbalance disrupts normal red blood cell development, leading to chronic anaemia, ineffective erythropoiesis, and increased iron absorption. Many patients require regular blood transfusions and long-term management of iron overload to prevent damage to vital organs such as the heart and liver.

Sickle cell disease is caused by a single mutation in the β-globin gene that produces haemoglobin S. Under low-oxygen conditions, red blood cells become rigid and adopt a sickle shape. These abnormal cells can block small blood vessels, causing severe pain episodes, chronic inflammation, and progressive organ damage.

Our research seeks to understand how inflammatory processes shape disease evolution in haemoglobin disorders. In particular, we investigate how abnormal haemoglobin production, chronic inflammation, and dysregulated iron metabolism alter the haematopoietic microenvironment and disrupt normal blood cell development. By integrating molecular biology, immunology, and genomic approaches, our work aims to define the mechanisms that drive disease progression and complications in these conditions. Advances in molecular medicine, gene therapy, genome editing and targeted therapeutics are creating new opportunities to translate these insights into improved treatments and, ultimately, curative strategies for individuals living with thalassaemia and sickle cell disease.