George Yousef

Dr. Yousef is the Program Medical Director of the Laboratory Medicine Program at the University Health Network.

His research laboratory is one of the leading laboratories focusing on the cancer biomarkers in renal cell carcinoma and prostate cancer using an integrated genomic, quantitative proteomic, transcriptomic and miRNA approaches with extensive bioinformatics analysis. His laboratory is also internationally recognized in miRNA research. In addition, he also published extensively about the discovery of kallikrein family of tumor markers and their roles as cancer biomarkers.

Dr. Yousef is a founding member of the International Scientific Committee of Kallikreins and was the chair of the 5th international symposium on Kallikreins in 2013. He is also the Vice President of the International Society of Enzymology.

He has over 200 published research papers and review articles and 15 book chapters. He is the editor-in-Chief of the Canadian Journal of Pathology and serves as a reviewer for over 40 journals. He is also the editor of a book on “Molecular Pathology in Cancer”. He serves as a reviewer for many national and international granting agencies.

He has served on numerous academic and governmental advisory committees, including the international kallikrein nomenclature Committee and the International Society of Urologic Pathology Kidney Cancer Classification in 2012. He is also a co-leader of the Kidney Cancer Research Network of Canada personalized medicine initiative; and member of the steering committee for prostate cancer management in Ontario.

At the pathology education frontier, he is a member of the Royal College Examination Board in Anatomical pathology and is leading the committee to digitalize the Royal College exam in Pathology. He is also a founding member and Chair of Pathology Informatics at the Canadian Association of Pathologists; His research was recognized by prestigious awards from the Royal College of Physicians, Canadian Association of Pathologists, and the United States National Academy of Clinical Chemistry.

Research Synopsis

My laboratory is focusing on understanding the pathogenesis of urologic tumors including renal cell carcinoma and prostate cancer using an integrated genomic, quantitative proteomic, transcriptomic and miRNA approach with extensive bioinformatics analysis, for the purpose of biomarker discovery, understanding mechanisms of drug resistance, and the development of new targeted therapy.

The objective of my research program is to achieve a new era of personalized medicine in urological malignancies, including kidney and prostate cancers.  A significant challenge in our current management system of cancer is that we divide patients into large cohorts based on the organ of origin or morphology of the tumour cells and then apply the same management plan to all patients. This results in a significant morbidity from complications and side effects because of the lack of our ability to choose the right treatment for the right patient. It also results in significant loss of resources. The promise of personalized medicine is to customize the management plan to fit the individual needs of each patient according to the biological behavior of the tumor which can be determined through molecular analysis.

My goal in the upcoming years is to connect pieces of the puzzle together by in depth analysis of tumour aggressive behaviour and resistance to therapy using animal models. My lab will continue to validate our diagnostic and prognostic markers and take it to the next phase of measuring these potential markers as non invasive serum and urine testing for kidney and prostate cancer. The future of kidney and prostate cancer research holds a lot of promise of upcoming revolutionary changes that will significantly improve patient outcome, and this will be done through integrated molecular analysis, a direction in which my lab is moving forward with confidence.

My research program has two parallel directions that merge together to reach an epoch of personalized medicine in kidney cancer; 1) the identification of molecular biomarkers for urological malignancies and, 2) the discovery of new molecular-based targeted therapy In the first direction, my lab has made a number of significant discoveries, as follows:I identified a number of miRNAs that can distinguish between normal kidney and kidney cancer patients with high accuracy. We are now testing these miRNAs as serum and urine non-invasive biomarkers.  This was published in the official journal of the American Urological Association and I hold a patent for this discovery which can have a huge impact towards improving the diagnosis of kidney cancer since the current diagnostic tools including imaging studies and biopsy are not always accurate and suffer a number of limitations and complications. Moreover, we were also the first to identify miRNA signature that can distinguish between the common subtypes of renal cell carcinoma 

Selected Publications

Rotondo F, Butz H, Syro LV, Yousef GM, Di Ieva A, Restrepo LM, Quintanar-Stephano A, Berczi I, Kovacs K. Arginine vasopressin (AVP): a review of its historical perspectives, current research and multifunctional role in the hypothalamo-hypophysial system. Pituitary. 2016 Jan 13. 2016 Jan. Senior Responsible Author.

Wegman DW, Ghasemi F, Stasheuski AS, Khorshidi A, Yang BB, Liu SK, Yousef GM, Krylov SN. Achieving Single-Nucleotide Specificity in Direct Quantitative Analysis of Multiple microRNAs (DQAMmiR). Anal Chem. 2016 Jan 12. [Epub ahead of print]. 2016 Jan. PMID: 26756139. Coauthor or Collaborator.

Luchini C, Veronese N, Solmi M, Cho H, Kim JH, Chou A, Gill AJ, Faraj SF, Chaux A, Netto GJ, Nakayama K, Kyo S, Lee SY, Kim DW, Yousef GM, Scorilas A, Nelson GS, Köbel M, Kalloger SE, Schaeffer DF, Yan HB, Liu F, Yokoyama Y, Zhang X, Pang D, Lichner Z, Sergi G, Manzato E, Capelli P, Wood LD, Scarpa A, Correll CU. Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis. Oncotarget. 2015 Nov;6(36):39088-39097. Coauthor or Collaborator.

Wala SJ, Karamchandani JR, Saleeb R, Evans A, Ding Q, Ibrahim R, Jewett M, Pasic M, Finelli A, Pace K, Lianidou E, Yousef GM. An integrated genomic analysis of papillary renal cell carcinoma type 1 uncovers the role of focal adhesion and extracellular matrix pathways. Mol Oncol. 2015 Oct;9(8):1667-1677. pii: S1574-7891(15)00095-2. doi: 10.1016/j.molonc.2015.04.007. [Epub ahead of print]. Senior Responsible Author.

Saleeb R, Faragalla H, Yousef GM, Stewart R, Streutker CJ. Malignancies arising in allograft kidneys, with a first reported translocation RCC post-transplantation: A case series. Pathol Res Pract. 2015 Aug 30;211(8):584-587. . doi: 10.1016/j.prp.2015.04.009. Coauthor or Collaborator.

White-Al Habeeb NM, Di Meo A, Scorilas A, Rotondo F, Masui O, Seivwright A, Gabril M, Girgis AH, Jewett MA, Yousef GM. Alpha-enolase is a potential prognostic marker in clear cell renal cell carcinoma. Clin Exp Metastasis. 2015 Aug;32(6):531-541. doi: 10.1007/s10585-015-9725-2. Epub 2015 Jun 3. Senior Responsible Author.

Kolin DL, Sy K, Rotondo F, Bassily MN, Kovacs K, Brezden-Masley C, Streutker CJ, Yousef GM. Prognostic significance of human tissue kallikrein-related peptidases 11 and 15 in gastric cancer. Tumour Biol. 2015 Jul 30;[Epub ahead of  print]. Senior Responsible Author.

Khella HW, Butz H, Ding Q, Rotondo F, Evans KR, Kupchak P, Dharsee M, Latif A, Pasic MD, Lianidou E, Bjarnason GA, Yousef GM. miR-221/222 are Involved in Response to Sunitinib Treatment in Metastatic Renal Cell Carcinoma. Mol Ther. 2015 Jul 23;23(11):1748-1758. PMID: 26224476. Senior Responsible Author.

Di Meo A, Rotondo F, Kovacs K, Cusimano MD, Syro LV, Di Ieva A, Diamandis EP, Yousef GM. Human Kallikrein 10 Expression in Surgically Removed Human Pituitary Corticotroph Adenomas: An Immunohistochemical Study. Appl Immunohistochem Mol Morphol. 2015 Jul;23(6):433-437. Senior Responsible Author.

Lichner Z, Ding Q, Samaan S, Saleh C, Nasser A, Al-Haddad S, Samuel JN, Fleshner NE, Stephan C, Jung K, Yousef GM. miRNAs Dysregulated in Association with Gleason Grade Regulate Extracellular Matrix, Cytoskeleton and Androgen Receptor Pathways. J Pathol. 2015 May 26;doi: 10.1002/path.4568. [Epub ahead of print]. Senior Responsible Author.

Butz H, Szabó PM, Khella HW, Nofech-Mozes R, Patocs A, Yousef GM. miRNA-target network reveals miR-124 as a key miRNA contributing to clear cell renal cell carcinoma aggressive behaviour by targeting CAV1 and FLOT1. Oncotarget. 2015 May;6(14):12543-12557. Senior Responsible Author.

Iakovleva G, Iakovlev V, Ordon M, Srigley J, Yousef GM. Tubulocystic carcinoma of kidney: a challenging diagnostic entity mimicking multicystic kidney and presenting with bone metastasis. Histopathology. 2015 May;66(6):892-894. doi: 10.1111/his.12502. Senior Responsible Author.

Papadopoulos EI, Yousef GM, Scorilas A. Gemcitabine impacts differentially on bladder and kidney cancer cells: distinct modulations in the expression patterns of apoptosis-related microRNAs and BCL2 family genes. Tumour Biol. 2015 May;36(5):3197-6207. doi: 10.1007/s13277-014-2190-8. Coauthor or Collaborator.

Rotondo F, Di Ieva A, Kovacs K, Cusimano MD, Syro LV, Diamandis EP, Yousef GM. Human kallikrein 10 in surgically removed human pituitary adenomas. Hormones (Athens). 2015 Apr;14(2):272-279. doi: 10.14310/horm.2002.1558. Senior Responsible Author.

Papadopoulos EI, Yousef GM, Scorilas A. Cytotoxic activity of sunitinib and everolimus in Caki-1 renal cancer cells is accompanied by modulations in the expression of apoptosis-related microRNA clusters and BCL2 family genes. Biomed Pharmacother. 2015 Jan 9;2015 Mar;70:33-40. doi: 10.1016/j.biopha.2014.12.043. Epub 2015 Jan 9. Coauthor or Collaborator.       

Honours and Awards

LMP Distinguished Service Award, Department of Laboratory Medicine & Pathobiology, University of Toronto (2021)