Role of SH2B1b in neuronal differentiation, survival and regeneration
(1) Signaling by neurotrophic factors
During neuronal differentiation, neuronal progenitor cells acquire specific morphological, biochemical, and physiological properties to become neurons. Neuronal differentiation occurs during development as well as during tissue remodeling in post-injury and disease state. Understanding the mechanisms of neuronal differentiation is key to innovative strategy for promoting neuronal regeneration. Research in our laboratory has focused on investigating how the adaptor protein SH2B1b (b isoform of SH2B1, previously known as SH2-Bb) promotes the nerve growth factor (NGF)-as well as fibroblast growth factor 1 (FGF1)-induced neuronal differentiation using the pre-neuronal PC12 cell line as a model. SH2B1b is a signaling adaptor protein known to regulate several signaling pathways. We are studying how SH2B1b differentially regulates NGF and FGF1 signaling and thus differentiation.
(2) Gene expression
SH2B1b has recently been shown to undergo nucleocytoplasmic shuttling suggesting its role in transcriptional regulation. We are studying how SH2B1b affects the expression of genes involved in neuronal differentiation. These genes include those that encode urokinase plaminogen activator receptor, matrix metalloproteinases 3 and 10, N-cadherin, neuronal cell adhesion molecule L1 and receptor protein tyrosine phosphatase etc.
(3) Cell survival and regeneration
An emerging direction in our laboratory is to study the role of SH2B1b in promoting neuronal survival and regeneration in response to stress and injury. Our efforts have been investigating whether SH2B1b affects signaling, gene expression and/or protein trafficking to promote cell survival and neuronal regeneration. Our ultimate goal is to validate whether SH2B1b-overexpressing neural stem cells will grant similar functions in promoting neuronal survival and regeneration. These results will be the basis to test the ability of SH2B1b in enhancing neuronal regeneration using an animal model of neuron degenerative diseases.
(4) Muscle differentiation
During muscle differentiation, myoblasts drop cell cycle and start the differentiation process. Myoblasts recognize each other and finally fuse to a multinucleated cell which response for contraction. These processes are interesting and many mechanisms are still unknown. Thus, besides neuronal differentiation, we also interested in muscle differentiation, a process containing rearrangement of actin cytoskeleton, membrane fusion and metabolism changes.