Ryan Dowling

Ryan Dowling, PhD

Dr. Ryan Dowling is an Affiliate Scientist at the Princess Margaret Cancer Centre. He earned his Bachelor of Science (2001) and Master of Science (2004) degrees from the University of Guelph and completed his Ph.D. in biochemistry (2009) at McGill University in the laboratory of Dr. Nahum Sonenberg. His research at McGill focused on the role of mTOR signalling in translational control and the anti-cancer effects of metformin, a common drug used for the treatment of diabetes.

After completion of his Ph.D., Ryan pursued postdoctoral training under the supervision of Dr. Vuk Stambolic at the Princess Margaret Cancer Centre where he was awarded a CIHR Banting Postdoctoral Fellowship. His work with Dr. Stambolic involved characterizing the clinical and biological effects of metformin in human breast cancer patients and assessing the role of the insulin receptor in obesity-associated cancers. In 2016, Ryan became an Affiliate Scientist at the Princess Margaret Cancer Centre where he continues to focus on insulin receptor signalling in human cancer using basic techniques in molecular biology as well as patient material from clinical trials. 

Obesity amongst the general population has been on a steady rise for the past 40 years and has become a significant health challenge worldwide. While it has long been recognized that obesity is a key risk factor in the etiology of type 2 diabetes and cardiovascular disease, emerging evidence indicates that obesity is an adverse factor in the development and severity of at least 13 different human cancers including those of the breast, prostate and colon.  It is estimated that obesity is associated with 20% of all cancer deaths in women and 14% of those in men. For example, overweight or obese women have an increased risk of breast cancer recurrence and death when compared to normal weight women. 
 
Obesity is often associated with a decrease in insulin sensitivity in insulin-target tissues and an increase in circulating insulin levels. Numerous lines of evidence suggest that insulin mediates the adverse effects of obesity in a number of cancers; however the strongest associations exist in breast cancer. My main research interest is the impact of obesity and insulin on breast cancer. In particular, I am investigating the response of cancer cells to insulin stimulation and characterizing the intracellular signaling pathways downstream of the insulin receptor. In addition, I am also interested in assessing the anti-cancer effects of metformin and identifying the molecular factors involved in mediating breast cancer sensitivity to this anti-diabetic drug. Using a translational approach that combines both basic and clinical research, I hope to increase our understanding of insulin and its effects on the cellular processes that underlie tumorigenesis. Given the potential 40% increase in the number of cancer cases in Canada over the next 15 years and escalating obesity rates, characterizing the impact of insulin on breast and other cancers will provide a strong foundation for improvements in cancer management from diagnosis to treatment and survivorship.  
 

J Clin Oncol. 2016 Dec 10;34(35):4249-4255
Lohmann AE, Goodwin PJ, Chlebowski RT, Pan K, Stambolic V, Dowling RJ
Cell Metab. 2016 Apr 12;23(4):567-8
Dowling RJ, Lam S, Bassi C, Mouaaz S, Aman A, Kiyota T, Al-Awar R, Goodwin PJ, Stambolic V
Breast Cancer Res. 2015 Mar 03;17:32
Dowling RJ, Niraula S, Chang MC, Done SJ, Ennis M, McCready DR, Leong WL, Escallon JM, Reedijk M, Goodwin PJ, Stambolic V
Breast Cancer Res Treat. 2015 Feb;150(1):149-55
Hadad SM, Coates P, Jordan LB, Dowling RJ, Chang MC, Done SJ, Purdie CA, Goodwin PJ, Stambolic V, Moulder-Thompson S, Thompson AM
Science. 2013 Jul 26;341(6144):395-9
Bassi C, Ho J, Srikumar T, Dowling RJ, Gorrini C, Miller SJ, Mak TW, Neel BG, Raught B, Stambolic V
Breast Cancer Res Treat. 2012 Oct;135(3):821-30
Niraula S, Dowling RJ, Ennis M, Chang MC, Done SJ, Hood N, Escallon J, Leong WL, McCready DR, Reedijk M, Stambolic V, Goodwin PJ
Nat Immunol. 2012 Apr 29;13(6):543-50
Herdy B, Jaramillo M, Svitkin YV, Rosenfeld AB, Kobayashi M, Walsh D, Alain T, Sean P, Robichaud N, Topisirovic I, Furic L, Dowling RJ, Sylvestre A, Rong L, Colina R, Costa-Mattioli M, Fritz JH, Olivier M, Brown E, Mohr I, Sonenberg N
J Mol Endocrinol. 2012 Jun;48(3):R31-43
Dowling RJ, Niraula S, Stambolic V, Goodwin PJ
BMC Med. 2011 Apr 06;9:33
Dowling RJ, Goodwin PJ, Stambolic V
Science. 2010 May 28;328(5982):1172-6
Dowling RJ, Topisirovic I, Alain T, Bidinosti M, Fonseca BD, Petroulakis E, Wang X, Larsson O, Selvaraj A, Liu Y, Kozma SC, Thomas G, Sonenberg N

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