Christopher D. Heinen, PhD

Colon cancer is the third most common malignancy in men and women and ranks behind only lung cancer in cancer deaths. The most common hereditary disease that predisposes patients to colorectal cancer is Lynch syndrome (LS) which stems from mutations in the mismatch repair (MMR) genes. In addition to its role in LS, flawed MMR has been implicated in 15-40% of sporadic colorectal and other extracolonic tumors indicating a more general role for MMR in tumor protection. Although many functional details of the MMR proteins have emerged, the mechanism by which flawed MMR contributes to tumorigenesis is not fully understood. Faulty MMR results in an elevated mutation rate (mutator phenotype), which has been proposed to lead to an accumulation of oncogene and tumor suppressor mutations that ultimately cause cancer. More recent work has revealed that MMR proteins play an important role in cell cycle arrest and apoptosis in response to certain DNA damaging agents. Thus, MMR mutations may affect tumorigenesis through multiple mechanisms. Our laboratory is interested in understanding what functions of the MMR system are affected during tumorigenesis.

[2025] A Cell-Based Functional Assay Calibrated for Analysis of MSH6 and MSH2 Mismatch Repair Gene Variants. [2023] Functional and phenotypic consequences of an unusual inversion in MSH2.