Leonardo A. Meza-Zepeda's project group Translational Genomics
The translational genomics group aims to understand cancer genome biology, by studying the genetic events that control gene expression in cancer. We aim to identify and characterise key regulatory mechanisms, molecules, and pathways that play a role in tumour development and progression, with the ultimate goal to translate this genomic knowledge to improve patient treatment and care.
Throughout the years our group has pioneered the establishment of numerous high-throughput based methods to study genome structure, dynamics and function. Together with bioinformatics approaches, we integrate large genome-wide data sets to identify mechanisms that regulate gene expression, and drivers of tumourigenesis, as well as drug resistence in soft tissue and bone tumours.
The blood plasma of cancer patients carries small amounts of fragmented circulating cell-free DNA (cfDNA) of tumour origin (ctDNA), which are released to the bloodstream through necrosis and apoptosis. The ctDNA represents in principle every cancer cell within the body and using a blood sample as a “liquid biopsy” allows non-invasive means to obtain tumour material for molecular analyses, thus circumventing the limitation of traditional biopsies. Our group has established a number of high-throughput sequencing methods to study liquid biopsies, which are used to monitor treatment response, disease evolution, and drug resistance in different types of soft tissue sarcomas. We aim to develop a less-invasive and more sensitive way of real-time monitoring of disease.
Imatinib treatment has been extremely successful in gastrointestinal stromal tumour (GIST) and represents a paradigm for the development of precision medicine in cancer . The majority of the patients show an initial treatment response, but over time the tumours evolve and develop resistance to the treatment. There is a clear need to expand our knowledge of how GISTs evolve and develop resistance in order to achieve more durable therapeutic responses. The overall objective is to reveal the mechanisms that GIST cells use to escape the imatinib treatment pressure.
We also participate in different collaborative efforts to implement advances genomic testing of cancer patients to drive precision cancer medicine in Norway. One of this efforst is InPreD, infrastructure for precision diagnostics, which delivers advanced diagnostics to stratify cancer patients into clinical trials..
Our research is fiannced by the Norwegian Cancer Society and the Southern and Eastern Norway Regional Health Authority