Proteomic profiling for proteins associated with intracranial atherosclerotic disease. - PROJECT SUMMARY/ABSTRACT Dr. Qing Hao is a vascular neurologist whose research focused on understanding the pathophysiology of intracranial atherosclerotic disease (ICAD) and risk stratification in ischemic stroke using a multimodal approach (neuroimaging and laboratory biomarkers), with the ultimate goal of investigating more efficacious stroke prevention strategies to improve clinical outcomes. The proposed training and mentored research will address critical gaps in her knowledge and research skills, and provide her with the foundation necessary to become a successful, independent clinical investigator in the field of cerebrovascular disease. Her training objectives are: 1) To master skills in applying proteomic approaches to patient-oriented clinical research; 2) To develop skills to independently integrate and analyze large-scale, complex, multimodal datasets; 3) To learn how to effectively conduct and lead collaborative clinical research projects, and progress toward an independent investigator. These training objectives will be achieved through carefully selected, highly relevant formal coursework, attendance at conferences, workshops, hands-on training on study design and management, data analysis, as well as guidance from her mentoring team. The proposed research project will to investigate the proteomic profile of ICAD in order to identify novel biomarkers associated with ICAD occurrence and ICAD plaque activity. Dr. Hao will first identify the proteins by direct tissue proteomics based on intracranial arterial samples, aiming to discover proteins and pathophysiological mechanisms that are highly specific to ICAD. Then she will examine the proteins from peripheral blood samples in ICAD subjects without stroke to identify proteins associated with ICAD occurrence, and in symptomatic ICAD subjects with acute stroke to identify proteins associated with active ICAD with high risk of causing clinical events. The findings from this K23 will enhance our understanding of the pathophysiological mechanism of ICAD, diagnosis and risk stratification, and ultimately enable novel therapeutic targets to minimize the risk of stoke recurrence and adverse outcome related to ICAD. The Icahn School of Medicine at Mount Sinai provides the ideal environment for Dr. Hao’s training and research needs, as she has assembled a team of mentors and collaborators who are internationally recognized experts in their fields and have incredibly strong mentorship track records. Her mentors and co-mentors are Dr. Bin Zhang (genomic and proteomic research), Dr. Rebecca Gottesman (cerebrovascular disease & clinical research), and Dr. Junmin Peng (multi-omics in biomedical research). Other faculty in the mentoring committee will offer distinct and complementary advices in area of proteomic research methodology, large scale data analysis and skills of leading a multidisciplinary research program. This comprehensive training approach afforded by K23 award will enable Dr. Hao to acquire essential knowledge and skills to implement the research, and to become a respected clinical investigator and leader in cerebral atherosclerotic disease and stroke.
