Catherine Adell O'Brien, MD, PhD, FRCSC

The focus of my research program is to develop a better understanding of the molecular pathways underlying the initiation and maintenance of colorectal cancers (CRCs). It is well established that cells within any given tumour display both functional and phenotypic heterogeneity. Experimental work over the past 50 years has also shown that not all cancer cells are created equal with respect to their ability to drive tumour growth; however, the biological basis for this observation remains to be fully elucidated. Our interest is to identify the molecular pathways responsible for driving tumour growth in the subset of CRC cells enriched for tumour-initiating capacity, also referred to as colorectal cancer-initiating cells (CC-ICs). Through identifying and characterizing the relevant molecular pathways we will also begin to understand the factors capable of modulating these survival pathways. One method we are using to better understand the survival mechanisms used by CC-ICs is through studying the molecular pathways they utilize to evade current chemotherapeutic strategies. By using functional genomic strategies to study CC-ICs, in the context of current chemotherapeutic agents, we are developing a better appreciation for the molecular pathways CC-ICs upregulate when exposed to standard of care chemotherapeutic agents. 

To better understand the factors driving CRC initiation we have commensed studies looking at a potential role for commensal bacterial flora in the intestinal tract.  Our ability to isolate intracellular bacteria from approximately one half of CRC samples derived from both patients and xenografts has led us to question whether these bacteria are playing a role in driving tumour initiation and/or maintenance. The existence of intracellular bacteria in CRC samples is well established, the question that remains to be answered is whether their presence is functionally relevant. We are interested in determining if commensal bacteria have a role in generating and maintaining CRCs and more specifically, CC-ICs.
 

JAMA Oncol. 2019 Apr 11;:
Kennedy ED, Simunovic M, Jhaveri K, Kirsch R, Brierley J, Drolet S, Brown C, Vos PM, Xiong W, MacLean T, Kanthan S, Stotland P, Raphael S, Chow G, O'Brien CA, Cho C, Streutker C, Wong R, Schmocker S, Liberman S, Reinhold C, Kopek N, Marcus V, Bouchard...
Nat Commun. 2019 03 29;10(1):1436
Lima-Fernandes E, Murison A, da Silva Medina T, Wang Y, Ma A, Leung C, Luciani GM, Haynes J, Pollett A, Zeller C, Duan S, Kreso A, Barsyte-Lovejoy D, Wouters BG, Jin J, Carvalho DD, Lupien M, Arrowsmith CH, O'Brien CA
Am J Physiol Endocrinol Metab. 2016 May 01;310(9):E762-73
Liu Y, Almeida M, Weinstein RS, O'Brien CA, Manolagas SC, Jilka RL
Sci Rep. 2019 Jan 29;9(1):842
Nixon AML, Duque A, Yelle N, McLaughlin M, Davoudi S, Pedley NM, Haynes J, Brown KR, Pan J, Hart T, Gilbert PM, Singh SK, O'Brien CA, Sidhu SS, Moffat J
PLoS Negl Trop Dis. 2018 Oct;12(10):e0006886
Colmant AMG, Hall-Mendelin S, Ritchie SA, Bielefeldt-Ohmann H, Harrison JJ, Newton ND, O'Brien CA, Cazier C, Johansen CA, Hobson-Peters J, Hall RA, van den Hurk AF
Bone Rep. 2018 Dec;9:61-73
Zimmerman SM, Heard-Lipsmeyer ME, Dimori M, Thostenson JD, Mannen EM, O'Brien CA, Morello R
Nat Commun. 2018 Jul 25;9(1):2909
Xiong J, Cawley K, Piemontese M, Fujiwara Y, Zhao H, Goellner JJ, O'Brien CA
Curr Osteoporos Rep. 2018 May 25;:
O'Brien CA, Morello R
Arch Virol. 2018 May 11;:
O'Brien CA, Hall-Mendelin S, Hobson-Peters J, Deliyannis G, Allen A, Lew-Tabor A, Rodriguez-Valle M, Barker D, Barker SC, Hall RA

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Assistant Professor, Department of Surgery, University of TorontO
Cross-appointment Faculty Member, Department of Physiology, University of Toronto 
General Surgeon, University Health Network, Toronto, Ontario - Speciality: surgical oncology, gastrointestinal malignancies