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个人简介
With my work team, we investigate on the crosstalk between extracellular signaling proteins and physical cues enabling stem cells (SC) to make decisions about fate (self-renewal versus differentiation; differentiation into specific cell types) and self-organization in space and time. We use human induced pluripotent stem cells (hiPSCs) as main cellular system. These SC types have unlimited in vitro self-renewal properties and the capability to differentiate into all cell body. Thus, hiPSCs have become are an excellent cellular system to ask the following questions: 1. how SC receive and process extracellular signaling proteins to make fate decisions; 2. how these biochemical signals interact with physical cues (spatial organization, cell shape and mechanical forces); 3. how these interactions produce distinct cellular responses.
Currently we have two related lines of work:
One line of our research aims at delineating key signaling processes controlling the undifferentiated state and self-renewal capacity of hiPSCs, and at developing methods to direct the differentiation of hiPSCs into clinically relevant cell types. Extensive emphasis is made on promoting dopaminergic neuron differentiation. We explore also new paradigms for cell replacement therapy for Parkinson’s disease aimed at improving functionality of transplanted cells and at preventing their in vivo tumorigenicity. For this research we combine cutting-edge neuronal differentiation protocols with brain transplantation in rat models of PD. We expect that this research may open new perspectives in regenerative medicine by developing more effective, user-friendly, and safe SC-based therapeutic strategies.
With the second line of investigation, we study the interplay between signalling dynamics and cell mechanics during early fate acquisition of hiPSCs. Our ongoing research has highlighted as local disruption of the hiPSC epithelial organization through apical constriction enables perception of differentiation signals by hiPSCs in these specific areas, and consequently the initiation of the cell differentiation process. These findings highlight that cell morphology in an epithelial tissue may be “a key driver” of spatial organization of signalling perception and differentiation events. We are coupling cell biology, biophysical approaches, imaging and physical force analysis to explore how these changes in epithelial morphology are established in mammals, how they regulate signal perception, and how they shapes morphogen gradients and tissue pattern.
研究兴趣
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SCIENTIFIC REPORTSno. 1 (2024): 5005-5005
Scientific Reportsno. 1 (2024): 1-7
Nature communicationsno. 1 (2023): 349-18
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