UBIQUITIN CARBOXYL TERMINAL HYDROLASE L1 (UCH-L1) AND VASCULAR LESION FORMATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The central hypothesis of the project is that deubiquitinating enzyme UCH-L1 is an essential regulator of vascular lesion formation. The proposal will uncover a novel mechanism that UCH-L1 serves as a key molecule in assembling inflammatory signaling complex thereby fine tuning vascular inflammatory responses and lesion formation. It is our view that the outcome will provide novel insight into the understanding of the complex sequelae of inflammation in vascular lesion formation. Our hypothesis will be tested by uitilzing UCH-L1 gain- and loss-of-function approaches in vitro and in vivo to address three specific aims as follows; Aim 1. Define an essential role of UCH-L1 in regulating VSMC inflammation in vitro Aim 2. Define molecular mechanism of UCH-L1-mediated inhibition of VSMC inflammation in virto Aim 3. Determine an essential role of UCHL1 in regulating VSMC inflammation and vascular lesion formation in vivo