In 2008 nearly 150,000 cases of colorectal cancer will be diagnosed in the United States, while nearly 50,000 people will die from the disease. The key to overcoming colorectal cancer is early detection, as treatments for early stages of disease are readily available and highly effective. Existing screening methods tend to suffer from poor specificity or cause significant patient discomfort. As a result, many cases of colorectal cancer go undetected until relatively late stages when the prognosis is comparatively grim. If a more convenient and specific means of colorectal cancer detection were available, many lives could be saved.
Over the past fifteen years or so, advances in mass spectrometry instrumentation, computational resources, and experimental techniques have led to the development of proteomics: the study of global patterns of protein expression and modifications under a wide array of biological conditions. Today, using state-of-the-art mass spectrometry and proteomics techniques, hundreds or thousands of proteins can be routinely identified and quantified from even complex biological samples such as tissue extracts and serum.
I am now working with Professor William Dove of Oncology, and Professor Michael Sussman of the Biochemistry department, to characterize the Min mouse on a proteomic level. Individual Min mice have a loss-of-function mutation in one copy of their Adenomatous Polyposis Coli gene, which predisposes them to development of many tumors in their intestinal tract at an early age. We are using a variety of quantitative proteomics techniques, including metabolic labeling with stable isotopes, to compare protein abundances in tumor versus normal colonic and intestinal tissues. We are also surveying serum proteins in an effort to identify any that are differentially expressed. This work should improve our understanding of the molecular basis of tumor development and should reveal wider physiological effects of tumor formation. We may also identify proteins that could serve as possible diagnostic or prognostic biomarkers for colorectal tumor development.