Catherine Adell O'Brien

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.
 
Aging Cell. 2017 Aug;16(4):693-703
Kim HN, Chang J, Shao L, Han L, Iyer S, Manolagas SC, O'Brien CA, Jilka RL, Zhou D, Almeida M
Cell Metab. 2017 Oct 17;:
Bauer PV, Duca FA, Waise TMZ, Rasmussen BA, Abraham MA, Dranse HJ, Puri A, O'Brien CA, Lam TKT
Endocrinology. 2017 Sep 14;:
Weinstein RS, Hogan EA, Borrelli MJ, Liachenko S, O'Brien CA, Manolagas SC
J Immunol. 2017 May 15;198(10):4054-4061
O'Brien CA, Overall C, Konradt C, O'Hara Hall AC, Hayes NW, Wagage S, John B, Christian DA, Hunter CA, Harris TH
Viruses. 2016 May 20;8(5):
Harrison JJ, Warrilow D, McLean BJ, Watterson D, O'Brien CA, Colmant AM, Johansen CA, Barnard RT, Hall-Mendelin S, Davis SS, Hall RA, Hobson-Peters J
JCI Insight. 2017 Sep 07;2(17):
Piemontese M, Almeida M, Robling AG, Kim HN, Xiong J, Thostenson JD, Weinstein RS, Manolagas SC, O'Brien CA, Jilka RL
J Steroid Biochem Mol Biol. 2017 Jun 09;:
Lee SM, Meyer MB, Benkusky NA, O'Brien CA, Pike JW
Hum Mol Genet. 2017 Feb 15;26(4):686-701
Fil D, DeLoach A, Yadav S, Alkam D, MacNicol M, Singh A, Compadre CM, Goellner JJ, O'Brien CA, Fahmi T, Basnakian AG, Calingasan NY, Klessner JL, Beal FM, Peters OM, Metterville J, Brown RH, Ling KKY, Rigo F, Ozdinler PH, Kiaei M
Am J Physiol Endocrinol Metab. 2016 Sep 01;311(3):E587-93
Piemontese M, Xiong J, Fujiwara Y, Thostenson JD, O'Brien CA
J Biol Chem. 2016 Nov 25;291(48):24838-24850
Fujiwara Y, Piemontese M, Liu Y, Thostenson JD, Xiong J, O'Brien CA

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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