Molecular Genetics

My main research interest is on the molecular genetics and cellular pathogenic mechanisms of motor and sensorimotor neuropathies. I identified the hot-spot residue in the small heat-shock protein 22 causing distal motor neuropathy (distal HMN). Interestingly, we found mutations in the HSP22 molecular partner, another small heat shock protein encoded by HSP27 - to be associated with distal HMN and CMT2F. These mutations target amino acids critical for the structural and functional integrity of this protein superfamily. I truly became fascinated to understand the biology behind ubiquitous expressed proteins resulting in a specific peripheral phenotype. My current project focuses on the elucidation of the mechanisms of mutated HSP22/HSP27-induced neuronal and axonal dysfunction and thus I am shifting my attention from genetics to cell and neurobiology. I aim to decipher why mutations in HSP22/HSP27 result in specific peripheral neuropathy and my hypothesis is that distal HMN might be as a result of cell death of motor neurons due to perikaryal atrophy, aggregation and axonal loss. Another mechanism might be alteration in axonal transport due to dysfunction of the cytoskeleton, impairment of energy production along the axon or synaptic dysfunction. Therefore, I will focus my research on the pleiotropic actions of stress proteins including chaperone-like activity, apoptotic pathways and cytoskeletal network.