Chemotherapy-induced cardiotoxicity (CIC) is a serious and prominent complication that limits the use of promising anti-cancer drugs as they eventually culminate to the development of heart failure. Although the appreciation of CIC has resulted in the establishment of cardio-oncology programs to manage these patients, our scientific understanding of the molecular signaling pathways involved in this condition is an ongoing challenge.
Leadership and collaborations
Dr. Sutendra is Associate Chair of Graduate Studies in the Department of Medicine. His research program involves collaborations with many investigators in the Cardiovascular Research Centre and at the Cancer Research Institute of Northern Alberta.
Dr. Sutendra is a facilitator and coordinator for the Master in Translational Medicine Program offered in the Department of Medicine, which comprises four different courses (MED 602, MED 604, MED 606 and MED 608).
Dr. Sutendra’s translational research program aims to develop novel therapies to not only selectively protect against various types of heart failure, but also have beneficial anti-tumor effects, in synergy with anti-cancer agents. Dr. Sutendra’s program has identified redox-sensitive metabolic proteins induced by chemotherapeutic agents in the myocardium that are candidates for therapeutic intervention with small molecule metabolic modulating compounds to simultaneously protect against chemotherapy-mediated apoptosis in the myocardium and decrease tumor growth. Many of the metabolic compounds Dr. Sutendra’s lab utilizes are commonly used in the clinic for other metabolic diseases, and therefore the translational potential of his program for patients with CIC is very high. Dr. Sutendra’s research is funded by Heart & Stroke Foundation of Canada, Canadian Institutes of Health Research, Canadian Foundation of Innovation and Alberta Innovates. He has over 40 publications in peer-reviewed journals.
Apoptosis, Cancer, Cardio-Oncology, Heart Failure, Metabolism, Redox
Selected Peer-Reviewed Publications:
- Saleme B, Zhang Z, Boukouris AE, Lorenzana-Carrillo MA, Jovel J, Wagg C, Lopaschuk GD, Michelakis ED and Sutendra G. A p53-mediated repression of the PGC1a and apelin receptor signalling pathways limit fatty acid oxidation energetics; implications for cardio-oncology. Journal of American Heart Association. doi.org/10.1161/JAHA.120.017247.
- Batran RA, Gopal K, Capozzi ME, Chahade JJ, Saleme B, Tabatabaei-Dakhili SA, Greenwell AA, Niu J, Almutairi M, Byrne NJ, Masson G, Kim R, Eaton F, Mulvihill EE, Garneau L, Masters AR, Desta Z, Velazques-Martinez CA, Aguer C, Crawford PA, Sutendra G, Campbell JE, Dyck JRB and Ussher JR. Pimozide alleviates hyperglycemia in diet-induced obesity by inhibiting skeletal muscle ketone oxidation. Cell Metabolism. 2020 April 6th pii: S1550-4131(20)30132-7.
- Tian L, Wu D, Dasgupta A, Chen KH, Mewburn J, Potus F, Lima PA, Hong Z, Zhao YY, Hindmarch C, Kutty S, Provencher S, Bonnet S, Sutendra G and Archer SL. Epigenetic metabolic reprogramming of right ventricular fibroblasts in pulmonary arterial hypertension: A pyruvate dehydrogenase kinase-dependent shift in mitochondrial metabolism promotes right ventricular fibrosis. Circulation Research. 2020 March 27th doi:10.1161/CIRCRESAHA.120.316443.
- Saleme B, Gurtu V, Zhang Y, Kinnaird A, Boukouris AE, Gopal K, Ussher JR and Sutendra G. Tissue-Specific Regulation of p53 by PKM2 is Redox-Dependent and Provides a Therapeutic Target for Anthracycline-Induced Cardiotoxicity. Science Translational Medicine. 2019 Feb 6; 11(478).
- Batran RA, Gopal K, Aburasayn H, Eshreif A, Almutairi M, Greenwell AA, Campbell SA, Saleme B, Court EA, Eaton F, Light PE, Sutendra G and Ussher JR. The antianginal ranolazine mitigates obesity-induced nonalcoholic fatty liver disease and increases hepatic pyruvate dehydrogenase activity. Journal of Clinical Investigation Insight. 2019; 4(1): e124643.
- Sutendra G* and Michelakis ED*. A metabolism-based, right ventricle-specific mechanism of heart failure. Heart and Metabolism. 2018 (77). *co-corresponding authors.
- Saleme, B and Sutendra G. A Similar Metabolic Profile Between the Failing Myocardium and Tumor Could Provide Alternative Therapeutic Targets in Chemotherapy-Induced Cardiotoxicity. Front Cardiovasc Med. 2018 Jun 11; 5:61.
- Dedeic Z#, Sutendra G#, Hu Y#, Chung K, Slee EA, White MJ, Zhou FY, Goldin RD, Ferguson DJP McAndrew D, Schneider JE and Lu X. Cell autonomous role of iASPP deficiency in causing cardiocutaneous disorders. Cell Death and Differentiation. Jul; 25(7) 2018. #These authors contributed equally to this work.
- Sutendra G* and Michelakis ED*. Oxygen Sensing in the Pulmonary Circulation: A Fluid State of Affairs. Circulation Research. 2017 August 4; 121(4): 323-325. *co-corresponding authors.
- Sutendra G* and Bonnet S*. The iron paradigm of pulmonary arterial hypertension: Popeye knows best. Circulation Research. 2015 May 8; 116(10):1636-1638. *co-corresponding authors.
- Sutendra G*, Kinnaird A, Dromparis P, Paulin R, Stenson TH, Haromy A, Hashimoto K, Zhang N, Flaim E and Michelakis ED*. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell. 2014 Jul 3; 158(1):84-97. *co-corresponding authors.
- Sutendra G, Dromparis P, Kinnaird A, Stenson TH, Haromy A, Parker JM, McMurtry MS and Michelakis ED. Mitochondrial activation by inhibition of PDKII suppresses HIF1 signaling and angiogenesis in cancer. Oncogene. 2013 Mar 28; 32(13): 1638-50.