Rare iron-related diseases encompass a broad spectrum of genetically and phenotypically distinct disorders, affecting both hematological and neurological systems. Examples include atransferrinemia and neurodegeneration with brain iron accumulation (NBIA). Despite their clinical impact, the pathophysiology of these conditions remains poorly understood, complicating diagnosis and treatment. 

The core focus of our current research is the discovery of profilin 2 (PFN2) as a novel IRP-regulated gene. Our group demonstrated that PFN2 is regulated by the IRP/IRE system, linking its expression to iron levels. PFN2 plays a vital role in cytoskeletal dynamics, mainly in actin polymerization that is important for neuronal function. A recent collaboration with researchers in Kiel, Germany, identified the first human case with PFN2 mutations, presenting with demyelinating peripheral neuropathy. My doctoral research will investigate PFN2’s role in this disease, building on prior findings that link reduced PFN2 levels to Charcot-Marie-Tooth disease. Additionally, we aim to elucidate how disruptions in iron metabolism influence peripheral neuronal function, cytoskeletal integrity, and myelination. 

The objectives are:

Scientific objectives:

1. Identification and analysis of additional cases to expand the dataset to enhance understanding of the condition and validate initial findings.
2. Characterize the role of PFN2 in this new form of demyelinating peripheral neuropathy and its connection with iron metabolism. We will also examine how PFN2 dysfunction disrupts iron metabolism, potentially impairing the myelination process and leading to the development of peripheral neuromuscular disorders.
3. Comprehensive documentation and dissemination of research findings through publications and collaborative exchanges.

Transfer and clinical objectives:

1. Commercialize Discoveries: Transfer findings to BLOODGENETICS for commercial exploitation, facilitating advancements in the diagnosis and treatment of iron-related diseases.
2. Enhance Clinical Management: Provide new insights into molecular pathways and genes implicated in iron metabolism, to enhance both clinical practices and therapeutic strategies for managing iron-related disorders.
3. Collaborate with International Research Groups: Strengthen partnerships with leading research groups, including the Institut für Genetik in Bonn, the University Medical Center Schleswig Holstein in Kiel (USHK), and the Vall d'Hebrón Research Institute, to further research on iron metabolism and demyelinating peripheral neuropathies.