Julian J. Lum

PhD

Dr. Julian J. Lum graduated with a PhD in Immunology from the University of Ottawa. He spent five years training at the University of Pennsylvania in the field of cancer biology with special emphasis on tumor metabolism. There he studied how cells adapt to nutrient stress and the role of autophagy in promoting cancer cell survival. In 2008, Dr. Lum returned to Canada and joined the Deeley Research Centre at BC Cancer where his current research interest is focused on the relationship between metabolism and impacts on immune responses in ovarian cancer. He is using mass spectrometry-based approaches to delineate the metabolomes of human patient samples. The goal is to identify potential targets that can be used to enhance immunotherapy for ovarian cancer. His core approach is to metabolomically engineer CAR-T cells using CRISPR-Cas-based gene-editing as way to overcome metabolic barriers in the tumor microenvironment. More broadly, he hopes the information gained from this work will enable a better understanding of how the tumor microenvironment influences the immune response to cancer. For more information about his lab, please click on his lab website: lumlab.ca.

Dr. Lum serves as the Director of the Metabolomics Consortium BC (Metabo-BC) , a network of metabolomic experts that provide the research community a core platform to conduct metabolomics research. This includes access to: human biospecimens, MS facilities, and customized guidance on development of research protocols, and data analytics.

Dr. Lum is an Associate Professor with the Department of Biochemistry and Microbiology, University of Victoria and Senior Scientist, BC Cancer. He is also the recipient of a CIHR New Investigator Award. His work is funded by the BC Cancer Foundation, CIHR, US Department of Defence, and Genome BC. Dr. Lum is Associate Editor of Biochemistry and Cell Biology.

Contact

jjlum@bccancer.bc.ca


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Lab Website

PubMed ID

ORCiD 

Projects

The Metabolic Ecosystem of Cancer and T Cells

Cancer cells and lymphocytes co-exist and interact in a dynamic environment. This kind of relationship is similar to ones in our nature environment. There are predators (cancer), prey (immune cell), and limited food sources (nutrients) that feed both predator and prey. Our laboratory is interrogating metabolite profiles of human ovarian cancers (e.g. tumors, T cells, serum, interstitial fluids) using a technology called mass-spectrometry to uncover the various nutrients present in the environment. Some nutrients are in competition while others are made by tumors cells and function to suppress the immune system. The overall goal is to identify potential immune suppressive nutrients or nutrients that may be limited due to competition. Once these targets are identified we will move them to Project #2 to genetically engineer T cells that will overcome these metabolic imbalances.

Researchers

  • Marisa Kilgour, BSc (PhD Candidate)
  • Tian Zhao, MSc (PhD Candidate)
  • Phineas Hamilton, PhD (Senior Research Associate)
  • Brad H. Nelson, PhD (Director, Deeley Research Centre)
  • Peter H. Watson, MD (Director, Tumor Tissue Repository)

Publications

1: MacPherson S, Kilgour M, Lum JJ. Understanding lymphocyte metabolism for use in cancer immunotherapy. FEBS J. 2018 Jul;285(14):2567-2578. doi: 10.1111/febs.14454. Epub 2018 Apr 17. PMID: 29611301.

 2: MacPherson S, Horkoff M, Gravel C, Hoffmann T, Zuber J, Lum JJ. STAT3 Regulation of Citrate Synthase Is Essential during the Initiation of Lymphocyte Cell Growth. Cell Rep. 2017 May 2;19(5):910-918. doi: 10.1016/j.celrep.2017.04.012. PMID: 28467904.

 3: DeVorkin L, Hattersley M, Kim P, Ries J, Spowart J, Anglesio MS, Levi SM, Huntsman DG, Amaravadi RK, Winkler JD, Tinker AV, Lum JJ. Autophagy Inhibition Enhances Sunitinib Efficacy in Clear Cell Ovarian Carcinoma. Mol Cancer Res. 2017 Mar;15(3):250-258. doi: 10.1158/1541-7786.MCR-16-0132. Epub 2017 Feb 9. PMID: 28184014; PMCID: PMC5451253.

 4: Townsend KN, Spowart JE, Huwait H, Eshragh S, West NR, Elrick MA, KallogerSE, Anglesio M, Watson PH, Huntsman DG, Lum JJ. Markers of T cell infiltrationand function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma. PLoS One. 2013 Dec 23;8(12):e82406. doi:10.1371/journal.pone.0082406. PMID: 24376535; PMCID: PMC3871161. 

5: Spowart JE, Townsend KN, Huwait H, Eshragh S, West NR, Ries JN, Kalloger S, Anglesio M, Gorski SM, Watson PH, Gilks CB, Huntsman DG, Lum JJ . The autophagy protein LC3A correlates with hypoxia and is a prognostic marker of patient survival in clear cell ovarian cancer. J Pathol. 2012 Dec;228(4):437-47. doi: 10.1002/path.4090. PMID: 22926683. 

6: Townsend KN, Hughson LR, Schlie K, Poon VI, Westerback A, Lum JJ. Autophagy inhibition in cancer therapy: metabolic considerations for antitumor immunity. Immunol Rev. 2012 Sep;249(1):176-94. doi: 10.1111/j.1600-065X.2012.01141.x. PMID: 22889222.

Engineering Designer CAR-T Cells

CAR-T cells have revolutionized how we approach treating cancers. However, they only work in a small number of patients. The environment created by the tumor presents a significant metabolic barrier for CAR-T cells to penetrate, survive, and function. Our research uses CRISPR-Cas9-based genome-editing technology to enhance the antitumor properties of CAR-T cells. A number of candidate metabolic genes are currently being tested (from Project #1). We expect to uncover further pathways that promote CAR-T cell efficacy in our metabolite profiling studies. This engineering approach will create designer CAR-T cells for testing in human clinical trials. We have also filed patent applications for our technology and top candidate from this project with the goal of commercialization.

Researchers

  • Gillian Carleton, BSc (PhD Candidate, CIHR Vanier Scholar)
  • Torin Halvorston (BSc Candidate)
  • Elaine Liu, MSc

Publications

1: DeVorkin L, Pavey N, Carleton G, Comber A, Ho C, Lim J, McNamara E, Huang H, Kim P, Zacharias LG, Mizushima N, Saitoh T, Akira S, Beckham W, Lorzadeh A, Moksa M, Cao Q, Murthy A, Hirst M, DeBerardinis RJ, Lum JJ. Autophagy Regulation of Metabolism Is Required for CD8+ T Cell Anti-tumor Immunity. Cell Rep. 2019 Apr 9;27(2):502-513.e5. doi: 10.1016/j.celrep.2019.03.037. PMID: 30970253.

2: Poffenberger MC, Metcalfe-Roach A, Aguilar E, Chen J, Hsu BE, Wong AH, Johnson RM, Flynn B, Samborska B, Ma EH, Gravel SP, Tonelli L, Devorkin L, Kim P, Hall A, Izreig S, Loginicheva E, Beauchemin N, Siegel PM, Artyomov MN, Lum JJ, Zogopoulos G, Blagih J, Jones RG. LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis. Science. 2018 Jul 27;361(6400):406-411. doi: 10.1126/science.aan3975. PMID: 30049881.


Improving Metabolic Fidelity during CAR-T Cell Manufacturing

 The process of manufacturing ‘clinic ready’ T cells for treating patients is highly complex. Further, the are no established methods that include metabolism in the criteria for evaluating predicted efficacy of CAR-T cells. Indeed, this manufacturing process is performed in an artificial system whereby CAR-T cells are grown in artificial conditions. We hypothesize that CAR-T cells become ‘addicted’ to these culture conditions and lose their metabolic fidelity after being infused into patients. We are using a technique called stable isotope labeling coupled with mass-spectrometry to establish the metabolic behavior of CAR-T cells throughout the manufacturing process. This information will then be used to tailor the processing steps such that the release product is primed for high efficacy upon reaching the tumor microenvironment. Top candidates from Project #2 will move into this pipeline of work.

Researchers

  • Sarah MacPherson, MSc
  • Dayna Clark (BSc Candidate)
  • BC Cancer Immunotherapy Program

Publications

1: MacPherson S, Kilgour M, Lum JJ. Understanding lymphocyte metabolism for use in cancer immunotherapy. FEBS J. 2018 Jul;285(14):2567-2578. doi: 10.1111/febs.14454. Epub 2018 Apr 17. PMID: 29611301.

Radiation and Immunotherapy Clinical Trials

Radiation therapy is the most common type of treatment for cancer. In most jurisdictions, greater than 50% of all patients receive some form of radiation during the course of their care. There is unequivocal evidence that radiation has immune stimulating properties and this can be harnessed by combining radiation with immunotherapy. However, it is unclear which type of radiation is most appropriate, at what time it should be delivered, and which immunotherapy drug it should be delivered in combination with.

With our clinical team, we launched the first Phase 1 Safety Clinical Trial combining external beam radiation with anti-PDL-1 therapy in ovarian cancer. The study is ongoing and we plan to conduct a comprehensive analysis of biospecimens collected as part of this trial. 

We are also studying the impact of brachytherapy and radionuclide therapy on immune responses. Brachytherapy is a type of radiation treatment that involves surgical implantation of radioactive “seeds” into the tumor. While radionuclide therapy involves the use of different particles of radiation that are attached to targeting molecules (e.g. peptides, antibodies) that bind to cancer cells. In this way, a ‘radiation payload’ is given to the tumor that will subsequently prime the immune system through a process called immunogenic cell death.

Researchers

  • Nathalie Costie, BSc
  • Abraham Alexander, MD
  • Wayne Beckham, PhD
  • Francois Benard, MD
  • Anna V. Tinker, MD
  • Peter Lim, MD
  • Juanita Crook, MD
  • Andrew I. Jirasek, PhD (UBC-Okanagan)
  • Alexandre Brolo, PhD (UVIC)
  • Mira Keyes, MD
  • Kevin Bennewith, PhD

Publications

1: Van Nest SJ, Nicholson LM, Pavey N, Hindi MN, Brolo AG, Jirasek A, Lum JJ.  Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer. BMC Cancer. 2019 May 20;19(1):474. doi: 10.1186/s12885-019-5686-1. PMID: 31109312; PMCID: PMC6528330.

2: Vrbik I, Van Nest SJ, Meksiarun P, Loeppky J, Brolo A, Lum JJ, Jirasek A. Haralick texture feature analysis for quantifying radiation response heterogeneity in murine models observed using Raman spectroscopic mapping. PLoS One. 2019 Feb 15;14(2):e0212225. doi: 10.1371/journal.pone.0212225. PMID: 30768630; PMCID: PMC6377107.

3: Van Nest SJ, Nicholson LM, DeVorkin L, Brolo AG, Lum JJ , Jirasek A. Raman Spectroscopic Signatures Reveal Distinct Biochemical and Temporal Changes in Irradiated Human Breast Adenocarcinoma Xenografts. Radiat Res. 2018 May;189(5):497-504. doi: 10.1667/RR15003.1. Epub 2018 Feb 23. PMID: 29474157.

4: Joe MB, Lum JJ , Watson PH, Tonseth RP, McGhie JP, Truong PT. Radiation generates an abscopal response and complete resolution of metastatic squamous cell carcinoma of the anal canal: a case report. J Gastrointest Oncol. 2017 Dec;8(6):E84-E89. doi: 10.21037/jgo.2017.06.15. PMID: 29299375; PMCID: PMC5750188.

5: Kalina JL, Neilson DS, Comber AP, Rauw JM, Alexander AS, Vergidis J, Lum JJ.  Immune Modulation by Androgen Deprivation and Radiation Therapy: Implications for Prostate Cancer Immunotherapy. Cancers (Basel). 2017 Jan 27;9(2):13. doi: 10.3390/cancers9020013. PMID: 28134800; PMCID: PMC5332936.

6: Johnson LD, Nesslinger NJ, Blood PA, Chima N, Richier LR, Ludgate C, Pai HH, Lim JT, Nelson BH, Vlachaki MT, Lum JJ . Tumor-associated autoantibodies correlate with poor outcome in prostate cancer patients treated with androgen deprivation and external beam radiation therapy. Oncoimmunology. 2014 Jun 25;3:e29243. doi: 10.4161/onci.29243. PMID: 25114831; PMCID: PMC4125379.