Marco Marra

Genome mapping and sequencing

Marra developed fingerprinting methods for analyzing large-insert cloned DNA segments. Working with collaborators, he applied these techniques to construct comprehensive genome maps to fuel genome sequencing. Along with GSC co-director Steven J.M. Jones, Marra was involved in "A physical map of the human genome", which describes the construction and use of the human genome map to fuel human genome sequencing. His fingerprinting approach was instrumental in organizing the international Human Genome Project, where the use of clone fingerprints to coordinate and fuel the public consortium's sequencing efforts distinguished it from parallel efforts. Using these methods, Marra's team generated over 5 million fingerprints for 63 different species, enabling genome sequencing beyond that of the human, including key biomedical, agricultural and industrial model organisms such as the mouse, the rat and Arabidopsis.

SARS coronavirus sequencing

In 2003, when severe acute respiratory syndrome (SARS) emerged as a global health threat, Marra led the group that first sequenced the SARS coronavirus genome. The work was completed in approximately six days after receipt of a sample from Canada's National Microbiology Laboratory in Winnipeg, and was recognized as a significant achievement in rapid viral genomics that contributed to understanding the etiology of the disease. The rapid sequencing demonstrated that this approach could serve as a tool to identify emerging infectious diseases and stimulated the rapid production of a vaccine by the SARS Accelerated Vaccine Initiative (SAVI) in British Columbia. Later work from the centre identified an alternative procedure for extracting nucleic acids for COVID-19 testing.

Next-generation sequencing methods

Marra's group was among the first international centres to receive Solexa next-generation sequencing instruments, in 2006, and contributed to developing protocols and analysis methods for the new technology. The group developed approaches for profiling small RNAs, including microRNAs, and for analyzing messenger RNA expression using massively parallel sequencing methods. The team also created widely used bioinformatics tools, including the Circos software, which became a standard visualization platform across genomics research and has appeared in numerous scientific publications and news media.

Precision cancer genomic medicine and cancer genomics

Shortly after the 2008 publication of the first cancer whole genome sequence, from a patient with acute myeloid leukemia, Marra and colleague Samuel Aparicio at UBC and BC Cancer were the first to sequence the whole genome of a solid cancer, from a breast cancer patient, identifying cancer-specific genetic mutations. In a 2010 study, as part of a GSC initiative, Marra's group demonstrated proof-of-concept for using whole genome and transcriptome sequencing to identify a cryptic cancer cell vulnerability and to apply a drug to exploit it, aligning an individual patient's genome profile with an off-label drug therapy. This work catalyzed the development of British Columbia's Personalized OncoGenomics (POG) program, which Marra currently co-leads with medical oncologist Dr. Janessa Laskin.

The POG program has enrolled thousands of cancer patients, using a comprehensive approach to precision cancer medicine that combines whole genome and transcriptome analysis with clinical data to search for personalized cancer treatments. Through this initiative, Marra's research has demonstrated the potential for cancer genome science to directly influence treatment selection and patient outcomes.

In addition to his work in precision cancer genomic medicine, Marra's cancer genomics research has identified recurrent mutations in many cancer types, including recurrently mutated genes. His work in B-cell lymphomas, including the identification of EZH2 mutations in follicular and diffuse large B-cell lymphomas and frequent mutation of histone-modifying genes in non-Hodgkin lymphoma, led to rationales for targeted therapeutic approaches and revealed epigenome dysregulation as a dominant feature of these cancers. Other work extended these approaches to pediatric cancers, demonstrating previously unrecognized molecular heterogeneity in childhood malignancies.