He played a major role in establishing an association between genomic instability and loss of heterozygosity (LOH) in human cancers. He was the first to show that SMAD4 inactivation is a critical event during the late stages of colon cancer progression and sustained TGFss signaling events are required to maintain epigenetic memory during breast cancer progression. Dr Thiagalingam also proposed a simple minded multi-modular molecular network (MMMN) cancer progression model as a road map to visualize the various gene alterations in modules of networks of pathways. His long-term goal is to identify novel cancer biomarkers and therapeutic targets by contributing to the 'big picture' of interconnected networks of events that mediate cancer progression to metastasis using breast and colon cancers as the model systems.