Bush, Jonathan
BSc (Brandon), MD (Manitoba), FRCPC (Manitoba), DABP (Northwestern)
Academic Rank(s): Clinical Associate Professor, UBC, Department of Pathology and Laboratory Medicine | Pathology Residency Program Director | Pediatric and Perinatal Pathologist, BC Children’s Hospital and Women’s Hospital | Co-Director, BC Children’s Hospital Biobank / @BCCHBioBank | Invesitgator, BC Children’s Hospital Research Institute
Affiliation(s): BCCH / BCCHRI
Research and Scholarly Interests: Sarcoma, pediatric bone tumors, novel diagnostic and precision methods in pediatric tumors, study of the immune microenvironment in tumors, development of patient-derived xenografts and chorioallantoic membrane (CAM) modeling for tumor research and drug testing
Clinical Interests: Pediatric and perinatal pathology, including bone tumors and sarcomas. Proteogenomics to understand inter and intra-tumoral heterogeneity in various pediatric cancers
I became interested in pathology, and specifically pediatric pathology, in medical school after being involved in a research project that explored transcription factors in retinoblastoma with Dr. David Eisenstat in Manitoba, and a subsequent ocular pathology medical elective with Dr. Miguel Burnier Jr in Montreal. Once in my anatomical pathology residency, I continued to pursue pediatric pathology but also took an interest in leadership, administration, and quality improvement. This led me to Chicago where I worked under a fantastic group of mentors including Pauline Chou, Mike Fritsch, Hector Melin, and Linda Ernst. I was lucky to find a job in my wife’s hometown of Vancouver, where I practice general pediatric and perinatal pathology with particular clinical and research interests in pediatric tumors including osteosarcoma, gastrointestinal diseases including eosinophilic disorders, and developmental and perinatal pathology including congenital heart anomalies. Bear Down! Go Cubbies!
Academic Background
- BSc (Hons) – Brandon University, Brandon Manitoba Canada, 2005
- MD – University of Manitoba, Winnipeg Manitoba Canada, 2009
- BSc (Med) – University of Manitoba, Winnipeg Manitoba Canada, 2009
- FRCPC – Anatomical Pathology, University of Manitoba, Winnipeg Manitoba Canada, 2014
- Pediatric Pathology Fellowship, Ann and Robert H Lurie Children’s Hospital of Chicago, Northwestern University, Chicago Illinois USA, 2015
Awards and Recognition
- UBC Science Co-op Supervisor Recognition Award – 2022
Publications
Research Interest
My research interests are diverse but focused. I have a firm interest in bone tumors and a soft spot for soft tissue sarcomas, including understanding the underlying pathophysiology and translational work in the clinical pathology lab setting. I joined the 2019-2021 cohort within the Children’s Oncology Group Young Investigator Program with a focus in the bone tumor group. I also am interested in exploring cell signaling and cell-to-cell communication through conventional molecular and proteomic analysis with fellow investigators. My second area of research interest is in gastrointestinal pathology, particularly eosinophilic esophagitis (EoE). Through these EoE projects, I enjoyed expanding my experience in immunology which builds on an interest during my fellowship at Lurie Children’s Hospital of Chicago, which explored transplant immunology and the effect on the gastrointestinal tract. I also enjoy expanding my experience in the area of transplant immunology. My last primary area of interest is in developmental pathology, which often stems from identifying common pathologic findings in the interesting cases I encounter at BC Children’s and Women’s Hospital. I have an interest in leadership and administration, which blossomed during my time as Cohort 2 in the BC Patient Safety and Quality Council’s Clinician Quality Academy.
Current Projects In My Lab Include
- Pediatric Bone Tumors The Bush lab uses fresh and fixed tumor tissue from the two most common malignant bone tumors, Osteosarcoma (OS) and Ewing Sarcoma (ES), to explore novel antibodies using immunohistochemistry (IHC) for diagnosis and prognosis. This includes developing tissue microarrays (TMAs) to test a number of antibodies across a wide variety of samples. Some work has shown that a particular methylation pattern in the diagnostic biopsies of OS may predict good or bad disease behaviour.
- SWI/SNF and Rhabdoid Tumors (RTs) Rhabdoid tumors are a group of primitive cancers that are often highly aggressive and are generally defined by a mutation in the SWI/SNF pathway, including the genes SMARCB1 (INI1) and SMARCA4 (BRG1). The Bush lab was one of the first groups to explore the use of BRG1 IHC to identify a subset of RTs that were INI1-retained. Further work is ongoing looking at the immune microenvironment of RTs as these are generally considered to have low tumor mutational burden and thus are immune-cold tumors, yet there appears to be heterogenous areas of tumor cell infiltration. Utilizing spatial genomics and proteomics, we hope to better understand RT inter and intra-tumoral heterogeneity.
- Novel Diagnostic Techniques in Pediatric Tumors Working with collaborators, the Bush lab is helping to establish a proteomics pipeline that will demonstrate the utility of proteomics in clinical applications. This includes providing diagnostic, prognostic, and in some cases predictive markers that will allow for personalized therapies based on relative over or under-abundance of particular proteins. Promising results have been seen in OS and neuroblastoma to date. In collaboration with researchers at UBC and the NIH, the Bush lab is exploring the use of machine learning (ML) in osteosarcoma. This work will develop a pipeline for assessing tissue quality for the purpose of molecular studies, facilitate histologic classification of OS for clinical trials, and to explore potential prognostic markers as identified by supervised and unsupervised ML.
- Precision Oncology The Bush lab has worked with collaborators in establishing a novel method of developing patient-derived xenografts using a less expensive model than the typical mouse system. Through this chorioallantoic membrane (CAM) modelling system, we have been able to facilitate tumor expansion in both highly aggressive and indolent tumors, and have worked to demonstrate the utility of the CAM system for drug testing.
- Eosinophilic Esophagitis (EoE) Our group was the first to show that pediatric EoE was associated with increased lamina propria IgG4-positive plasma cells, which is being explored as to whether food-specific IgG4 can be used to evaluate for EoE disease activity. Ongoing work by the Bush lab has included utilizing novel techniques to evaluate EoE slides as well as potential spatial differences between the immune and squamous cell compartments.
- Perinatal, Placental, and Autopsy Pathology The Bush lab continues to have an interest in a number of additional projects, including the pathology seen in placenta, stillbirth pathology, and family/caregiver experiences in sudden death in infancy and childhood.
Teaching Interest
- After being a regular teacher to anatomical pathology (AP) residents, I became a member of the UBC AP Competency Committee since 2018, and became the AP Residency Training Program Director in 2022. I was the lead applicant and Working Group co-Chair for the Pediatric and Perinatal Pathology (PPP) Area of Focused Competency (AFC) application and development, and subsequently took the role of Vice-Chair of the PPP AFC in 2022. I also teach at the undergraduate (PATH304) and graduate (PATH501) level within the Department of Pathology and Laboratory Medicine and elsewhere (MEDG421) within the UBC system.