Studying genetic mechanisms of treatment resistance in non-Hodgkin lymphomas

Dr. Morin's research program will develop and apply laboratory and computational genomic methodologies that use DNA sequencing and other sensitive platforms to study the drivers of tumour onset, progression and treatment resistance in solid cancers in order to understand the somatic drivers of non-Hodgkin lymphomas (NHLs). Using massively parallel (next-generation) DNA and RNA sequencing, Dr. Morin will be able to identify somatic alterations and gene expression signatures in tumour tissue and liquid biopsies (circulating tumour DNA). To properly study such large data sets, he will utilize cutting-edge bioinformatics techniques and develop novel analytical approaches and pipelines that will allow leverage of unique sample processing techniques and applications.

Moving forward, this research will investigate aggressive subtypes of NHL including patients who typically fail standard-of-care treatments. Dr. Morin will rely on features of this malignancy such as high somatic point mutation rate, a well established list of known lymphoma-related genes, and the presence of clonal immunoglobulin rearrangements to develop assays to study the genetics of specimens from NHL patients in various ways. These include deep sequencing using a novel molecular barcoding system and digital PCR-based methods. He will continue to push the limits of sequencing technology by applying deep sequencing and whole exome sequencing to circulating tumour DNA. Under this research program, he will also continue to use a variety of laboratory and computational approaches to understand the clonal structure of NHLs, especially in the context of serial samples collected over the course of disease progression and after treatment failure or relapse. 

Dr. Morin's lab, along with the BC Cancer Agency, plan to pursue options to commercialize these strategies so that a broader group of users can use these techniques for research and clinical applications. Some of the research under this program will involve evaluating the performance of novel ctDNA-based methods to study tumour genetics and evaluate treatment responsiveness. This will be conducted in the context of prospective and retrospective samples from multi-centre clinical trials in Canada. This engagement with clinicians and publications describing these trials will help accelerate the adoption of such emerging technologies to the clinic.