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 collaboraions with many investigators in the cardiovascular research core and at the Cross Cancer Institute in the investigation of novel therapies against CIC.
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 CIC, but also have beneficial anti-tumor effects, in synergy with anti-cancer agents. One of the challenges in designing CIC therapies is selectively protecting the myocardium without hindering chemotherapy-mediated tumor regression. An intriguing difference between the myocardial and the tumor microenvironments is that the myocardium is normoxic (i.e. oxidized) and the tumor hypoxic (i.e. reduced). Thus, Dr. Sutendra’s lab investigates redox-sensitive proteins, induced by chemotherapeutic agents in the myocardium, as potential therapeutic targets in CIC. The advantage of his program is that it would allow for selectively preventing myocardial apoptosis without interfering with tumor suppression.
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 and Alberta Innovates. He has 32 publications in peer-reviewed journals.
Apoptosis, Cancer, Cardio-Oncology, Heart Failure, Metabolism, Redox
Selected Peer-Reviewed Publications:
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. Jun 11, 5: 61, 2018.
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*, 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.
Sutendra G, Dromparis P, Wright P, Bonnet S, Haromy A, Hao Z, McMurtry MS, Michalak M, Vance JE, Sessa WC and Michelakis ED. The role of Nogo and the mitochondria-endoplasmic reticulum unit in pulmonary hypertension. Science Translational Medicine. 2011 Jun 22; 3(88):88ra55.
Metabolic Modulation as a Novel Therapy for
- Funding Source: Heart & Stroke Foundation of Canada
- Year Granted: 2018
- Research Role: Principal Investigator