Proteomics Biomarker Development Laboratory

The Biomarker Development Laboratory is primarily focused on the development of biomarkers for the early detection of three types of adenocarcinomas: lung, colon and pancreas using proteomics.  The major approach implemented is based on evidence that a humoral response to protein antigens may predate a clinical diagnosis of cancer, indicating the utility of serum assays of specific tumor protein antigens or their corresponding auto-antibodies, for the early detection of cancer.  Of relevance is that direct cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer.  However, direct mass spectrometric profiling has difficulties in identify in distinctive proteins and yielding reproducible patterns.  We hypothesize that distinctive profiles result from differential expression of relatively abundant serum proteins.  Therefore, it is proposed to develop and implement antibody microarrays that target a wide range of serum proteins and proteins that are differentially expressed in lung cancer, to measure the abundance of their respective proteins in serum samples from newly diagnosed lung cancer patients, from healthy controls, from patients with chronic obstructive pulmonary disease (COPD) and from subjects with other types of cancer as controls.   

Proteomic Technologies Eastern Research Resources Consortium

The goal of the Proteomic Technologies Eastern Research Resources Consortium is to build a resource that facilitates the development of infrastructure that will enable protein biomarker discovery in cancer.  The consortium consists of investigators with broad expertise including cancer biology and epidemiology and cancer biomarkers, mouse models of cancer, proteomics, protein microarrays, informatics and data integration.  It is proposed to critically assess the merits of a spectrum of proteomic strategies for the comprehensive profiling of plasma for the purpose of uncovering potential cancer biomarkers.  The mouse plasma proteome data obtained in this project, will be integrated with human plasma proteome data currently being collected through the efforts of a large number of laboratories that are participating in the Human Proteome Organization’s Plasma Proteome Project.  The consortium is expected to deliver a resource that will enable protein biomarker discovery in cancer.

Novartis Collaboration

The objective of the proteomic studies is to undertake exploratory parallel testing of peripheral blood and bone marrow on a limited basis for some 25 patients.  The goal is to determine which proteomic analyses is the most useful in identifying potential markers that predict response to Gleevec.  Three different proteomic approaches will be used for identifying potential markers that predict response to Gleevec, markers of Gleevec effect and potential markers of toxicity.

The approaches listed below will be utilized given the exploratory nature of the proteomic investigations:

-    Profiling of plasma by multi-dimensional separations

-    Quantitative analysis of separated proteins

-    Identification of proteins of interest by mass spectrometry

-    Functional profiling