Assistant Professor in the Departments of Pathology & Laboratory Medicine, and Medical Genetics
Cumming School of Medicine
HM 205, 3330 Hospital Drive NW
Calgary AB T2N 4N1
My laboratory studies congenital and childhood malformations, overgrowths, and tumors; focusing on those involving the skeletal, vascular, and connective tissue systems of the body. These conditions can range from localized lumps & discolorations to widespread, life-threatening growths. Most are believed to result from non-heritable, low-level somatic mutations acquired early in development that subsequently affect normal developmental programming, signaling, and patterning. Depending on the genetic background, developmental timing, cell type(s), and extent of this new genetic alteration, the affected tissue(s) can develop into disordered, maturing, slowly proliferative masses (malformations and overgrowths), or fail to fully mature from an embryonic state and develop into (pre)malignant masses. While masses can develop at single sites, they can also involve multiple sites of the body due to somatic mosaicism for the acquired mutation.
During the last decade, we have utilized next-generation technologies to determine the genetic basis for ten malformation and/or tumor disorders involving skeletal, connective tissue, and/or vascular development. I have been particularly interested in adapting technologies (massively parallel sequencing, ddPCR, single cell omics analyses) for use in archival paraffin material, as this is often the only source of lesional tissue available for rare disease research (mutations cannot be readily detected in blood or other bodily fluids). Animal models (mouse, zebrafish) have been developed with collaborators for some of these disorders to better understand the biology as well as to develop and test novel therapeutic approaches. Our discovery of somatic mosaic mutations in PIK3CA as the cause of lymphatic anomalies and combined vascular anomaly/ overgrowth syndromes has led to the widespread and successful use of sirolimus for treatment of affected patients, as well as trials of more targeted therapies. We have recently developed ddPCR-based assays for research and clinical testing that are capable of detecting single-digit mutant allele frequencies, a phenomenon that is not uncommon in these conditions and previously undetectable by available technologies.
Currently, our lab is studying a recently described class of aggressive childhood vascular malformations (kaposiform types) that, based on clinical behavior and outcomes, blur the traditional lines between a malformation and malignant process. We have sequenced tissues from several affected patients with the hope of better defining these entities, modeling their disease processes in the lab, and identifying desperately needed therapeutics for affected children. Additionally, we are planning to use single cell omics approaches to better understand how overgrowths and malformations can develop and sustain growth given the low copy number of mutant allele in lesional tissues. Finally, as a practicing pediatric pathologist, I maintain several collaborative projects involving biomarker identification for other pediatric solid tumors.