Giannakis Lab Research

We have ongoing research activities in the following areas:
 

Determinants of Immunotherapy Response and Resistance in Colorectal Cancer

A primary focus of our lab is to study the tumor microenvironment in colorectal cancer and the cell types, oncomicrobes,and molecular pathways that mediate immunotherapy resistance in this disease. To this end, we use a multitude of approaches including immunogenomic, microbiomic and pathologic analyses of specimens from patients with colorectal cancer, characterizing the human colorectal atlas at single-cell level resolution and generating patient-derived organoid models for functional studies. Our research efforts are enhanced by translational studies on biospecimens from patients with colorectal cancer receiving immunotherapies at the Dana-Farber Cancer Institute.

Integrative Molecular Epidemiology Studies of Colorectal Cancer 

We have comprehensively characterized over one-thousand colorectal tumors collected from two exquisitely annotated prospective cohort studies. Through the integration of Whole Exome Sequencing, RNA-Seq, pathologic, microbial and epidemiologic data we aim to gain insights into the pathophysiology of colorectal cancer, its interplay with dietary and other macroenvironmental factors and devise novel treatment and prevention strategies for this disease.

The Role of RNF43 in Colorectal Cancer Pathogenesis and Immunomodulation

Our group previously identified pathogenic mutations in RNF43, an E3 ubiquitin ligase participating in the Wnt-signaling pathway in over 18% of colorectal tumors and demonstrated immune exclusion in colorectal cancers with active Wnt-signaling. We also described that the most frequent RNF43 mutation, RNF43 G659fs, activates PI3K signaling instead. We are now employing functional genomic, immunologic and pharmacologic assays to further study the role of RNF43 in colorectal cancer and its microenvironment.