Academic Rank:
Associate Professor, Pathology and Laboratory Medicine, Faculty of Medicine, UBC
Senior Scientist, Integrative Oncology, BC Cancer Agency
Affiliation(s):
Short Bio:

Dr. Lockwood received his BSc. in Microbiology and Immunology from the University of British Columbia (2004) and completed his Ph.D. in Pathology and Laboratory Medicine (2009) at the same university, training with the lung cancer research group at BC Cancer Research Centre where he aimed to characterize the genetic mechanisms underlying development of different lung cancer subtypes. He pursued postdoctoral studies as a CIHR Jean-Francois St. Dennis Fellow in Cancer Research in the laboratory of Nobel laureate Dr. Harold Varmus, first at Memorial Sloan-Kettering Cancer Center, New York, and later at the National Human Genome Research Institute in Bethesda, MD. There, he focused on utilizing mouse models of lung cancer to study mechanism of lung cancer initiation, progression and response to therapy and identifying novel therapeutics for lung cancer treatment. Dr. Lockwood returned to the BC Cancer Research Institute to begin his own research group in 2014 with a focus on understanding lung cancer biology using integrative genomics approaches. His lab has specific interest in dissecting genes and signalling pathways that drive lung cancer development and targeted therapy resistance, using both model systems and genomic data from patients for this purpose. He is the recent recipient of the Michael Smith Foundation for Health Research Scholar and the International Association for the Study of Lung Cancer Young Investigator awards.

Academic background

  • Post-Doctoral Fellow (Cancer Genetics), with Harold Varmus, National Human Genome Research Institute, 2010-2014
  • Post-Doctoral Fellow (Cancer Biology and Genetics), with Harold Varmus, Memorial Sloan-Kettering Cancer Center, 2009-2010
  • PhD (Pathology and Laboratory Medicine), University of British Columbia, 2009
  • BSc (Microbiology and Immunology), University of British Columbia, 2004

Awards and Recognition

  • Michael Smith Foundation for Health Research Scholar Award. 2014-2019
  • CIHR Jean-Francois St. Dennis Fellowship in Cancer Research. 2010-2013
  • Postdoctoral Fellowship. Canadian Institutes of Health Research. 2010-2013
  • Research Trainee Award (Senior). Michael Smith Fdn Health Research. 2008-2010
  • International Association for the Study of Lung Cancer Young Investigator Award. 2009
  • BCCA Betty Rice Memorial Award for Lung Cancer Research. 2008
  • Canadian Graduate Scholarship (Doctoral). NSERC Canada. 2006-2008
  • Research Trainee Award (Junior). Michael Smith Fdn Health Research. 2006-2008
  • Postgraduate Scholarship. NSERC Canada. 2004-2006

Publications

Recent Publications:

  • Johnson F, Ferrarone J, Liu A, Brandstädter C, Munuganti R, Farnsworth D, Lu D, Luu J, Sihota T, Jansen S, Nagelberg A, Shi R, Forcina GC, Zhang X, Cheng GSW, Spencer Miko SE; de Rappard- Yuswack G, Sorensen PH, Dixon SJ, Guha U, Becker K, Djaballah H, Somwar R, Varmus H, Morin GB, Lockwood WW. (2022). Characterization of a small molecule inhibitor of disulfide reductases that induces oxidative stress and lethality in lung cancer cells. Cell Rep. 2022 Feb 8;38(6):110343. SA.
  • Lu D, Nagelberg A, Chow J, Chen YT, Michalchuk Q, Somwar R, Lockwood WW (2022) MET exon 14 splice-site mutations preferentially activate KRAS signaling to drive tumorigenesis. Cancers. In Press.
  • Calder J, Luu J, Nagelberg A, Lu D, Lockwood WW (2021) Resistance to BET inhibitors in lung adenocarcinoma is mediated by caesin kinase phosphoylation of BRD4. Oncogenesis. 10(3): 27. SA.
  • Inoue Y, Nikolic A, Farnsworth D, Liu A, Ladanyi M, Somwar R, Gallo M, Lockwood WW. (2021). Extracellular signal-regulated kinase mediates chromatin rewiring and lineage transformation in lung cancer. eLife. 10: e66524. SA.
  • Melese ES, Franks E, Cederberg RA, Harbourne BT, Shi R, Wadsworth BJ, Collier JL, Halvorsen EC, Johnson F, Luu J, Oh MH, Lam V, Krystal G, Hoover SB, Raffeld M, Simpson RM, Unni AM, Lam WL, Lam S, Abraham N, Bennewith KL*, Lockwood WW* (2022) CCL5 production in lung cancer cells leads to an altered immune microenvironment and promotes tumor development, OncoImmunology, 11:1. *Co-Senior Author.
  • Deng H, Liu H, De Silva T, Xue Z, Mohamud Y, Qu J, Zhang J, Jia W, Lockwood WW*, Luo H* (2019) Coxsackievirus Type B3 is A Potent Oncolytic Virus Against KRAS-Mutant Lung Adenocarcinoma. Molecular Therapy – Oncolytics. 4:266-278 [*co-senior author] SA.
  • O’Farrell H, Harbourne B, Kurlawala Z, Inoue Y, Nagelberg A, Martinez V, Oh MH, Coe B, Thu K, Lam S, Lam W, Unni AM, Beverly L, Lockwood WW (2019) Integrative genomic analysis identifies GGA2 as a cooperative driver of EGFR mediated lung tumorigenesis. Journal of Thoracic Oncology. 14(4):656-671. SA.

Link to Dr. Lockwood’s Google Scholar Profile: https://scholar.google.ca/citations?user=He7XywkAAAAJ&hl=en .

Research Interest

  • Lung cancer
  • genomics
  • drug discovery
  • mouse models
  • cell lineage
  • oncogene signaling
  • immune response

Research Program

Lung cancer is the leading cause of cancer mortality worldwide, suffering from a late stage of disease at the time of diagnosis and a paucity of effective therapeutic strategies to treat advanced tumours. However, with our increasing understanding of lung cancer biology has come the advent of targeted therapies to combat this devastating disease. These therapies target mutated components of key cellular pathways on which tumours have become dependent on for survival, yielding drastic initial response rates without the major side effects of traditional chemotherapies. Despite these successes two major problems remain: first, the majority of lung cancer patients have tumours without mutations in targetable genes and; second, all patients eventually develop resistance to treatment with these targeted agents. In addition, since lung tumours commonly have hundreds of mutated genes, it is difficult to pinpoint those that are responsible for tumour growth and resistance to therapy, creating a clear bottleneck in the translation of laboratory findings to a clinical setting.

My lab utilizes an integrative strategy to address these issues. Through analysis of the genomic profiles of human lung tumours, we aim to identify novel genes and pathways that are altered during lung cancer development. Furthermore, by combining this information with the characterization of mice genetically engineered to develop lung tumours, we attempt to elucidate the key genes driving lung cancer initiation, progression and response to therapy. Lastly, by screening libraries of chemical compounds across lung cancer cells, we aim to characterize novel inhibitors of these identified genes and their corresponding pathways that show promise for use as targeted therapies. Together, this work will further our understanding of lung cancer biology and create insight toward the development of new approaches to diagnose and treat patients suffering from this disease.

 

Current projects in my lab include:

  • Directed Studies/Co-Op Students
  • MSc and PhD Students
  • Postdoctoral Fellows

Teaching Interest

  • Scientific communication and outreach
  • Cancer biology and treatment
  • Mechanisms and models of cancer

Dr. Lockwood teaches PATH531/MEDG521.