Our laboratory focuses on the risk stratification of colon cancer, novel treatment targets and mechanisms of colon cancer cell growth and metastasis. We are working on three distinct projects with varying degrees of overlap.
1) The modulation of growth suppressive and pro-migratory signaling in metastatic colon cancer. For this, we investigate SMAD-dependent and SMAD-independent signaling and their respective effects on colon cancer phenotype and outcome.
Previously, we have shown that the primary receptor of the growth suppressive TGF β family member activin, ACVR2, is mutated by different mechanisms in the two most common genomic subtypes of colon cancer. Activin signaling is both growth suppressive and pro-migratory and currently, we are assessing the effects of loss of activin signaling in vivo as well as the nature of the switch from growth suppressive to pro-migratory signaling with an emphasis on distinctive clinically relevant downstream effects distinguishing activin and TGF β signaling in colon cancer.
2) Tumor suppressive splice variant expression as biomarkers in colon cancer. For this we utilize various imaging techniques as well as Q-PCR on primary CRC samples to correlate splice variant expression of several tumor suppressors with colon cancer patient outcome. This will be follow-up by mechanistic studies.
3) Characterization of immunologic targets for colon cancer therapy and detection. To address these questions we are working on various cell surface display approaches including i) cDNA display for the identification of novel cell surface markers and ii) antibody surface display to generate new antibody candidates directed against promising colorectal cancer surface antigens.
To test our hypotheses, we are utilizing in vitro and in vivo models in conjunction with primary colon cancer specimens with clinical data, using databases generated through the PIs high risk colon cancer clinic at Northwestern to answer questions in a fully translational manner.