Selene Lomoio

Research/Areas of Interest: Alzheimer's disease (AD) accounts for approximately 70% of all cases of dementia. Currently, no cure or prevention for AD exists. During my predoctoral career, I conducted innovative studies on sporadic and familial AD mouse models aimed to elucidate the role of cerebellum in this pathology. Since I joined Dr. G. Tesco laboratory, I have been trying to comprehend the function of the protein GGA3 in both healthy and AD brains. I developed and advanced an innovative live cell imaging approach to investigate GGA3 trafficking in hippocampal neurons. I recently demonstrated that not only does GGA3 reside in axons, but fundamentally that this protein is essential for BACE1 trafficking regulation and homeostasis. Our current data demonstrate that GGA3 genetic deletion results in the accumulation of BACE1 in the axon of hippocampal neurons. Furthermore, we observed a general disruption of BACE1 axonal trafficking in GGA3 null neurons together with its accumulation in axonal swellings. We have also identified a novel AD-linked GGA3 loss of function mutation in late-onset AD patients. Altogether, our data demonstrate that GGA3 loss of function and consequent axonal accumulation of BACE1 initiate a cascade of events leading to AD-like axonopathy. Our studies provide a proof-of-concept that drugs aimed to preserve GGA3 function could be beneficial for AD treatment and/or prevention. Recently, I have been developing a new experimental approach to differentiate human neurons from iPSC derived from patient carrying familial AD mutations. I have already established a successful protocol to differentiate 2D iPSC-derived neuronal culture from these lines. Currently, I am collaborating with Dr. D. Kaplan to grow these neurons in silk-collagen protein scaffolds. This model is highly innovative. Differentiating neurons will grow in a donut-shaped porous silk sponge within an optically cleared collagen-filled central region which will allow, for the first time, live in vivo studies of a human Alzheimer's brain-like tissue during ageing under controlled experimental conditions.