The Comprehensive Proteome Characterization Center at Johns Hopkins: High Precision Discovery and Confirmation of Genoproteomic Targets

作为CPTAC现有的五个PCCs之一，我们建议利用我们已经建立的中心来进一步研究

As one of the five current CPTAC PCCs, we propose to leverage our established center to further our research in the comprehensive characterization of biospecimens from human and preclinical models for additional cancer types. We have assembled an outstanding team of basic and clinical scientists to discover and confirm proteins and protein modifications associated with cancer progression using genoproteomic approaches. This multidisciplinary team will be managed by the same three Principal Investigators (PI) and consists of internationally recognized experts in proteomic technologies, genomics, proteogenomics-specific bioinformatics, biostatistics, oncology, pathology, cancer biology, assay development, quality control, technology optimization, and clinical laboratory science/clinical chemistry. Our team has complementary and integrated expertise with previous and ongoing successful collaborations. The plan is to integrate the genomics findings with proteomic analysis (genoproteomics) and to overcome the caveats and challenges in the comprehensive understanding of tumor biology. We believe that genomic data provides a highly valuable molecular route towards the identification of genes and pathways that could be useful for the detection, differential diagnosis, outcome prediction and therapeutic targets of cancer. The proteomic approaches will provide the identification of unique features that are inherent to proteins including post-translational modifications, such as glycosylation and phosphorylation. We propose to use the technology platform validated during the current CPTAC which is high throughput, robust and state of the art. These technologies are proven, with the capability of generating reproducible results across labs. We will use a two-step strategy to characterize defined sets of genomically-characterized samples. The first step is the discovery of target proteins from both biological and clinical specimens using mass spectrometry and affinity based technologies. The second step is the confirmation of these targets using high-throughput, CPTAC Tier 2 analytically validated targeted assays, for example, Multiple Reaction Monitoring Mass Spectrometry (MRM-MS). In addition, we propose to develop pilot studies for technology improvement. The goal is to generate accurate, reproducible, sensitive, quantitative, and multiplexed assays using optimized and standardized high-throughput technologies for the discovered targets. While this PCC application is focused on the proteomic characterization of biological and clinical specimens, we believe that the understanding of and expertise in proteogenomic data analysis and translation will be critical for the success of the PCC and the overall CPTAC network. Investigators/PIs from our proposed PCC will be part of applications for the CPTAC Proteogenomic Data Analysis (PGDAC) and Translational Research (PTCR) Centers. Collaboration and team work are key to the success of the CPTAC program. With this multidisciplinary team of outstanding basic and clinical scientists, our PCC offers the best opportunity for the successful characterization of biological and clinical specimens to discover and confirm cancer targets to advance precision cancer medicine.