TUBEROUS SCLEROSIS COMPLEX
The MacKeigan lab works toward new therapeutic targets for cancer and tuberous sclerosis complex (TSC), a tumor syndrome characterized by mutations in TSC1 and TSC2. TSC presents a unique clinical problem, as the diversity of tumor burden in patients can vary dramatically, and clinicians have no way to predict which patients will be severely afflicted. Our laboratory used TSC patient specimens, sequencing technology, and bioinformatics analysis to characterize the disease's genomic landscape for 78 tumors from 5 clinical sites. Our resulting Nature Communications publication is the most comprehensive genomics study in the TSC field to date. Importantly, this work has led us to discover that germline variants are common among this patient cohort, which we believe may be a contributing factor to more severe disease. Further, our laboratory found that select compounds reduce the viability of TSC mutant cells, and reduce tumor burden in mouse models of TSC. Our goal is to determine how germline variants influence clinical diversity in TSC, and work to target these mutations for improved treatment approaches. Given the role of germline mutations in aggressive cancers, this research also has important implications for oncology.