Kelsie Thu

Dr Thu is a scientist at the Keenan Research Centre for Biomedical Science at St. Michael’s Hospital.

Her research program is focused on understanding the cell and molecular determinants of therapy response in lung cancer in order to develop improved therapeutic strategies for lung cancer patients.

She was born and raised in Maple Ridge, British Columbia and obtained her Bachelor’s degree at Simon Fraser University in Biological Sciences with a specialization in Cell and Molecular Biology.

She received her PhD in Interdisciplinary Oncology from the University of British Columbia under the supervision of Dr Wan Lam, where she used integrative, clinical genomic strategies to decipher mechanisms contributing to cancer biology.

As a postdoctoral fellow in Dr Tak Mak’s laboratory at the Princess Margaret Cancer Centre, Dr Thu used CRISPR/Cas9 functional genomics approaches to delineate mechanisms of drug response in cancer.

Research Synopsis

My laboratory is located at the state-of-the-art Li Ka Shing Knowledge Institute of St. Michael’s Hospital (209 Victoria St, Toronto, Ontario M5B 1T8).

Graduate students are enrolled in the Department of Laboratory Medicine and Pathobiology at the University of Toronto.

My research aims to decipher the biology of drug response in lung cancer in order to:

1. identify new therapeutic intervention points for circumventing drug resistance, and
2. develop novel strategies for making standard of care lung cancer treatments work more effectively.

The overall objective of my research is to make biological discoveries that can be translated into new therapeutic approaches that will improve lung cancer survival rates.

Students in the Thu laboratory will conduct genomic analyses to mine lung tumour datasets and utilize CRISPR/Cas9 technologies to study the effects of genetic manipulation on lung cancer drug response.

They will characterize drug response mechanisms and evaluate putative therapeutic strategies using in vitro tumour models as well as mouse models of lung cancer.

Research areas

Lung cancer is the number one cause of cancer death in Canada.

While new drugs have improved progression-free survival rates, the 5-year overall survival rate for lung cancer has not surpassed 18%.

Advanced stage at diagnosis, lack of therapies that elicit long-term responses, and development of therapy resistance remain significant barriers to improving patient outcomes.

Therapy resistance occurs in most lung cancer patients and for all treatment modalities including chemotherapy, targeted agents, and newly approved immunotherapies. Thus, research to identify new treatment strategies that produce durable responses and mitigate drug resistance are urgently needed to improve survival rates.

Enormous efforts have been dedicated to deciphering drug resistance mechanisms, however, the biology underlying resistance in many cases is not well understood.

Furthermore, while the identification of some resistance mechanisms can inform the next line of treatment, the best strategies for overcoming therapy resistance remain largely unknown.

My research is primarily focused on identifying and understanding the cell and molecular mechanisms governing lung cancer response to therapy.

This includes identifying novel cell intrinsic and extrinsic factors that dictate response to standard of care lung cancer treatments such as immunotherapies and targeted therapies, as well as investigating novel therapeutic vulnerabilities that can be targeted to potentiate the anti-tumour activity of lung cancer drugs or overcome drug resistance.

My research team uses an integrative platform involving clinical genomics, functional genomics, and a variety of in vitro and in vivo lung cancer models to unravel the biology of drug response.

Recent Publications

Kubli SP, Bassi C, Roux C, Wakeham A, Baniasadi SP, Duncan G, Palomero L, Thu KL, Cassetta L, Soong D, Lindzen M, Yarden Y, Herranz C, Lazaro C, Gobl C, Fang-chi M, Haight J, Tinto P, Silvester JS, Elliott M, Cescon D, Ramachandran P, Petit A, Pettersson S, Pollard JW, Pujana MA, Mak TW, Cappello P, Gorrini C (2019). AhR-AREG signaling shapes the tumour microenvironment to support BRCA1-associated carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America. 116(9): 3604-3613.

Zheng L, Chen Z, Kawakami M, Chen Y, Roszik J, Mustachio LM, Kurie JM, Villalobos PA, Lu W, Behren CM, Mino B, Solis LM, Silvester J, Thu KL, Cescon DW, Rodriguez-Canales J, Wistuba II, Mak TW, Liu X, Dmitrovsky E. Threonine tyrosine kinase inhibition eliminates lung cancers by augmenting apoptosis and aneuploidy. Molecular Cancer Therapeutics. 2019 Oct 18; 18(10):1775-1786.

O'Farrell H, Harbourne B, Kurlawala Z, Inoue Y, Nagelberg A, Martinez VD, Lu D, Oh MH, Coe BP, Thu KL, Somwar R, Lam S, Lam WL, Unni AM, Beverly L, Lockwood WW. Integrative genomic analyses identifies GGA2 as a cooperative driver of EGFR mediated lung tumorigenesis. Journal of Thoracic Oncology. 2019 Apr; 14(4): 656-671.

Thu KL, Silvester J, Elliott MJ, Ba-alawi W, Duncan MH, Elia AC, Mer AS, Smirnov P, Safikhani Z, Haibe-Kains B, Mak TW, Cescon DW. Disruption of the anaphase-promoting complex confers resistance to TTK inhibitors in triple-negative breast cancer. Proceedings of the National Academy of Sciences of the United States of America. 2018 Feb 13; 115(7):E1570-E1577.

Thu KL, Soria-Bretones I, Mak TW, Cescon DW. Targeting the cell cycle in breast cancer: towards the next phase. Cell Cycle. 2018 Sep 11; 17(15):1871-1885.

Kawakami M, Mustachio LM, Zheng L, Chen Y, Rodriguez-Canales J, Mino B, Kurie JM, Roszik J, Villalobos PA, Thu KL, Silvester J, Cescon DW, Wistuba II, Mak TW, Liu X, Dmitrovsky E. Reply to Oegema et al.: CFI-400945 and Polo-like kinase 4 inhibition. Proceedings of the National Academy of Sciences of the United States of America. 2018 Nov 13; 115(46): E10810-E10811.

Elliott MJ, Jerzak KJ, Cockburn JG, Safikhani Z, Gwynne WD, Hassell JA, Bane A, Silvester J, Thu KL, Habie-Kains B, Mak TW, Cescon D. The Antiarrhythmic Drug, Dronedarone, Demonstrates Cytotoxic Effects in Breast Cancer Independent of Thyroid Hormone Receptor Alpha 1 (THRa1) Antagonism. Scientific Reports. 2018 Nov 8; 8(1):16562.

Safikhani Z, Smirnov P, Thu KL, Silvester J, El-Hachem N, Quevedo R, Lupien M, Mak TW, Cescon D, Haibe-Kains B. Gene isoforms as expression-based biomarkers predictive of drug response in vitro. Nature Communications. 2017 Oct 24; 8(1):1126. doi: 10.1038/s41467-017-01153-8

Xu H, Di Antonio M, McKinney S, Mathew V, Ho B, O'Neil NJ, Santos ND, Silvester J, Wei V, Garcia J, Kabeer F, Lai D, Soriano P, Banath J, Chiu DS, Yap D, Le DD, Ye FB, Zhang A, Thu K, Soong J, Lin SC, Tsai AH, Osako T, Algara T, Saunders DN, Wong J, Xian J, Bally MB, Brenton JD, Brown GW, Shah SP, Cescon D, Mak TW, Caldas C, Stirling PC, Hieter P, Balasubramanian S, Aparicio S. CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumors. Nature Communications. 2017 Feb 17; 8:14432. doi: 10.1038/ncomms14432.

Bailey SD, Desai K, Kron KJ, Mazrooei P, Sinnott-Armstrong NA, Treloar AE, Dowar M, Thu KL, Cescon DW, Silvester J, Yang SY, Wu X, Pezo RC, Haibe-Kains B, Mak TW, Bedard PL, Pugh TJ, Sallari RC, Lupien M. Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer. Nature Genetics. 2016 Oct; 48(10):1260-6.

Thu KL, Papari-Zareei M, Statsny V, Song K, Peyton M, Martinez VD, Zhang YA, Castro IB, Varella-Garcia M, Liang H, Xing C, Kittler R, Milchgrub S, Castrillon DH, Davidson HL, Reynolds CP, Lam WL, Lea J, Gazdar AF. A comprehensively characterized cell line panel highly representative of clinical ovarian high-grade serous carcinomas. Oncotarget. 2016 Jun 10; 8(31):50489-50499.

Becker-Santos DD, Thu KL, English JC, Pikor LA, Martinez VD, Zhang M, Vucic EA, Luk MT, Carraro A, Korbelik J, Piga D, Lhomme NM, Tsay MJ, Yee J, MacAulay CE, Lam S, Lockwood WW, Robinson WP, Lam S, Jurisica I, Lam WL. Developmental transcription factor NFIB is a putative target of oncofetal miRNAs and is associated with tumour aggressiveness in lung adenocarcinoma. Journal of Pathology. 2016 Oct; 240(2):161-72.

Inoue S, Li WY, Tseng A, Beerman I, Bendall SC, Kron K, Elia AJ, Lemmonier F, Cescon DW, Hao Z, Lind EF, Takayama N, Planello A, Shen SY, Shih AH, Larsen DM, Li Q, Snow BE, Wakeham A, Gorrini C, Bassi C, Thu KL, Murakami K, Elford AR, Ueda T, Straley K, Yen K, Melino G, Cimmino L, Aifantis I, Levine RL, De Carvalho D, Lupien M, Rossi DJ, Nolan GP, Cairns RA, Mak TW.  Mutant IDH1 downregulates ATM and alters DNA repair and sensitivity to DNA damage independent of TET2. Cancer Cell. 2016 Aug 8; 30(2):337-348.

Dominguez-Brauer C, Thu KL, Mason JM, Blaser H, Bray MR, Mak TW (2015). Targeting Mitosis in Cancer: Emerging Strategies. Molecular Cell. 60(4):524-536.

Honours and Awards

Canada Research Chair (Tier 2), 2021