Research Discipline(s): Translational, Clinical
Primary Title: Radiation Oncologist, CancerCare Manitoba
Additional Titles & Affiliations: Associate Professor, Max Rady College of Medicine, Faculty of Health Sciences, Department of Radiology, Section of Radiation Oncology, University of Manitoba; Clinician Scientist, CancerCare Manitoba Research Institute
RESEARCH TOPICS
Lung Cancer, Esophageal Cancer, Metabolomics, MicroRNA and Radio Sensitivity, Mitophagy, Hematological Malignancies
CancerCare Manitoba
675 McDermot Ave, ON 3264
Winnipeg, MB R3E 0V9
Canada
What I have observed in my cancer patients in the clinic nourishes curiosity and discovery; and a promise of hope for future cancer patients.
Research Summary
There has been considerable progress in our understanding of lung cancer biology over the last two decades. Checkpoint inhibitors and the discovery of actionable driver mutations have changed the landscape of non–small cell lung cancer with significantly improved outcomes. While genomics, transcriptomics, and proteomics may predict the biological behavior of malignant cells, their metabolic alterations play a direct and vital role in tumor initiation, proliferation, and metastasis. Since 2015, as a principal investigator, I have been leading metabolomics research in lung cancer in collaboration with scientists and clinicians using nuclear magnetic resonance and liquid chromatography quadrupole time-of-flight mass spectrometry We believe metabolic signatures could be potential biomarkers of early disease detection, treatment response, and targets for pharmacological intervention.
Metastasis is the major cause of death in non-small cell lung cancer patients. There is a clear need for further understanding the process of metastasis, which may provide grounds for novel targeted drug discovery and personalized medicine. We plan to evaluate how Bcl2l13 is involved in the regulation of EMT via mitophagy in NSCLC cells, and how mitophagy regulates metastasis in human and animal cell models.
Attempts to understand an individual patient’s intrinsic radio sensitivity have been made by studying genetic phenotypes, such as single-nucleotide polymorphisms, and specific cytokines involved in the pathogenesis of radiation induced lung injury. There is an urgent need to develop novel biomarkers that are precise, personalized and definitively predict the intrinsic radio-sensitivity of individual patients. I am working to evaluate microRNA (miRNA) levels in plasma as a new biomarker to predict radiation-induced pulmonary toxicity.
Further, my research also focuses on incorporating artificial intelligence (AI) into radiation treatment planning for cancer patients.
Goals
- Early detection of lung cancer through non-invasive tools as a complement or to replace the existing low dose chest CT.
- Understand the altered metabolic pathways in the pathogenesis of lung cancer to discover novel biomarkers of prognosis and targets for treatment.
- Discover molecular biomarkers of radiation toxicity as potential targets for intervention to reduce radiation toxicity.
Research Biography
I completed my post graduate training in radiation oncology at McMaster University, Canada in 1996 and was a research fellow at the National Research Council of Canada in 1998-1999.
I am the lead investigator of several translational and clinical research projects since 2011and hold several research peer reviewed funded grants as the lead investigator.
I actively collaborate with diverse faculties at the University of Manitoba, the Health Sciences Centre, and the Albrechtsen Research Centre. On a national level, I collaborate with the Ontario Clinical Oncology Group to investigate the effects of the combination of metformin with chemo-radiotherapy in locally advanced lung cancer and SBRT in early-stage lung cancer. I have been the member of undergraduate medical student research programs at the University of Manitoba since 2017.
Achievements
- Leadership in developing the Stereotactic Body Radiotherapy (SBRT) Program for Lung Cancer at Cancer Care Manitoba.
- Leadership in developing the Small Animal Irradiation program at CancerCare Manitoba Research Institute.
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Featured Publications
- Metabolic Signatures of Lung Cancer in Sputum and Exhaled Breath Condensate Detected by 1H Magnetic Resonance Spectroscopy: A Feasibility Study. Magn Reson Insights. 2016 Nov 17; 9:29-35. doi: 10.4137/MRI.S40864. PMID: 27891048; PMCID: PMC5117486.
- Non-invasive exploration of metabolic profile of lung cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry. Contemp Clin Trials Commun. 2019 Sep 6;16:100445. doi: 10.1016/j.conctc.2019.100445. PMID: 31650068; PMCID: PMC6804748.
- Metabolic Changes in Early-Stage Non-Small Cell Lung Cancer Patients after Surgical Resection. Cancers (Basel). 2021 Jun 16;13(12):3012. doi: 10.3390/cancers13123012. PMID: 34208545; PMCID: PMC8234274.
- Metabolic Alterations in Sputum and Exhaled Breath Condensate of Early Stage Non-Small Cell Lung Cancer Patients After Surgical Resection: A Pilot Study. Front Oncol. 2022 Jun 3;12:874964. doi: 10.3389/fonc.2022.874964. PMID: 35719971; PMCID: PMC9204221.
- Metformin in Combination With Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer: The OCOG-ALMERA Randomized Clinical Trial. JAMA Oncol. 2021 Sep 1;7(9):1333-1341. doi: 10.1001/jamaoncol.2021.2328. PMID: 34323924; PMCID: PMC8323053.
- Outcome of Locally Advanced Esophageal Cancer Patients Treated With Perioperative Chemotherapy and Chemoradiotherapy Followed by Surgery. Am J Clin Oncol. 2021 Jan 1;44(1):10-17. doi: 10.1097/COC.0000000000000773. PMID: 33105233.
- When and Where to Discuss Do Not Resuscitate: A Prospective Study to Compare the Perceptions and Preferences of Patients, Caregivers, and Health Care Providers in a Multidisciplinary Lung Cancer Clinic. Cureus. 2015 Mar 12;7(3):e257. doi: 10.7759/cureus.257. PMID: 26180681; PMCID: PMC4494527.
- Does Motion Assessment With 4-Dimensional Computed Tomographic Imaging for Non-Small Cell Lung Cancer Radiotherapy Improve Target Volume Coverage? Clin Med Insights Oncol. 2017 Mar 14;11:1179554917698461. doi: 10.1177/1179554917698461. PMID: 28469512; PMCID: PMC5395259.
- Regulation of Autophagy via Carbohydrate and Lipid Metabolism in Cancer. Preprints 2023, 2023010183 (doi: 10.20944/preprints202301.0183.v1). In review.
