ANALYTICAL PROTEOMIC TEAM
Biomarker identification and characterization holds great promise for more precise diagnoses and for tailored therapies. The heterogeneity of human cancers and unmet needs for effective detection and treatment in these diseases provides a compelling argument to focus biomarker development in cancer. Mass spectrometry (MS)-based proteomics approaches have provided insight into biomarkers of cancer and other diseases with excellent sensitivity and high analytical precision. However, the results have proven difficult to reproduce, owing to the complexity of human biofluids and the protocols employed in these approaches.
Fred Regnier, Purdue’s John H. Law Distinguished Professor of Chemistry, is the principal investigator for the Purdue/IU Analytical Proteomics Team (APT) that has been approved as one of 5 National Centers in the new NCI program establishing a consortium for Clinical Proteomic Technology Assessment for Cancer (CPTAC). The team will develop robust protocols and standards for MS-based cancer proteomics employing both electrospray ionization (ESI) and Matrix Assisted Laser Desorption Ionization (MALDI) MS platforms and close cooperation between the Bindley and the Protein Analysis and Research Center (academic component of INCAPS) at the Indiana University School of Medicine (IUSOM). The start-up company Predictive Physiology and Medicine (PPM) will cooperate with David Clemmer’s group at IU Bloomington to provide ion mobility spectrometry evaluation. This proprietary IU technology adds several orders of magnitude increased dynamic range for cancer biomarker proteomics studies. Additional team members from Purdue, IUPUI and IU Bloomington provide the needed expertise and experience to manage, analyze and mine high-volume and high-complexity proteomics data.
APT cancer biologists provide a focus on candidate biomarker proteins found in the NFκB transcription factor and STAT3 signaling pathways of relevance for cancers of the breast and prostate. The consortium will employ nano-scale immunoaffinity columns prior to precise MS detection and quantification of specific candidate cancer protein biomarkers. The immunologic approach will be expanded with an emerging technology incorporating specific antibodies on a microfabricated optical disc that is read by spinning disc inferometry. This ‘bioCD’, invented at Purdue and licensed to local start-up company and APT partner Quadraspec, enables label-free evaluation of up to hundreds of analytes from up to hundreds of samples in minutes.
Data collection, management, analysis and mining are major bottlenecks for high throughput proteomics approaches. APT will take advantage of Purdue’s Discovery Pipeline (PDP) for high complexity data handling. The PDP was developed from a broad-based cooperation between the Bindley Bioscience, eEnterprise and Cyber Centers at Discovery Park and includes input, support and direction from faculty and staff scientist investigators across the Purdue campus.
Human blood samples for these studies will be collected under defined conditions and in accordance with rigorous sample collection parameters by the Hoosier Oncology Group (HOG), a network of oncologists across Indiana. Blood samples will be submitted to and organized by IUSOM physicians with extensive experience in performance of clinical trials. Prostate cancer samples will be made available from the NCI-sponsored Eastern Cooperative Oncology Group (ECOG) trial, whereas breast cancer patient and control samples will be collected specifically for this consortium at HOG sites throughout the State. Sample collection organized from IUSOM, the nation’s second largest and Indiana’s only medical school, ensures a diverse cross section of patient demographic groups as well as thorough standardization of the collection and storage processes. Participation from the consulting firm Safis Solutions will further ensure that data generation and documentation of sample analysis protocols are performed in compliance with FDA guidelines.
The goals of the program are to define existing technologies and to identify emerging technologies that will enable precise, sensitive and reproducible measurement of protein biomarkers in cancer. These biomarkers will ultimately be measured in the clinical setting and are expected to have dramatic positive impact for cancer diagnostics and therapeutics.