User:Sudharsan Periyasamy-Thandavan

•	Dr. Periyasamy-Thandavan’s work has made a significant influence to understand the molecular mechanism of pro-survival autophagy. Cisplatin is a widely used chemotherapy drug, with major side effects in kidneys, inducing acute kidney injury. Acute kidney injury is a typical condition of renal stress, leading to cell death, tissue damage, and loss of renal function or renal failure. Recently, Dr. Periyasamy-Thandavan succeeded in providing novel evidence that autophagy play a role in ameliorating the effects of acute injury on the kidney. He was the first researcher to demonstrate the cytoprotective role of autophagy in cisplatin nephrotoxicity. Cisplatin activates autophagy within renal tubular cells, and that inhibition of autophagy promotes apoptosis of cultured renal tubular cells treated with cisplatin. His findings were relevant to the potential protective role of autophagy in acute injury to other organs, such as brain, heart, and liver. He also involved with a study that highlighted the rapid decrease in autophagy markers post stroke injury indicating that modulation of autophagy may offer a new therapeutic avenue for stroke and other disease.

•	In a recent study, Dr. Periyasamy-Thandavan found that autophagy is critical to estrogen receptor positive (ER+) breast cancer cell survival and the development of antiestrogen resistance. Because crosstalk has been demonstrated between the autophagy- and proteasome-mediated pathways of protein degradation, Dr. Periyasamy-Thandavan investigated how the proteasome inhibitor bortezomib affects autophagy and cell survival in antiestrogen-treated ER+ breast cancer cells. Dr. Periyasamy-Thandavan showed that bortezomib at clinically achievable doses induced a significant death response in hormonally treated breast cancer cells with blockade of autophagy function as a major target. His study also demonstrated that bortezomib attenuated cathepsin L and B activity and that cathepsin activity is required for autolysosomal turnover of proteins in ER+ breast cancer cells. These findings provided the insights of combining an autophagy inhibitor with antiestrogen therapy to have therapeutic advantage in the management of early-stage breast cancer by modulating pro-survival autophagy.

•	Dr. Periyasamy-Thandavan’s work has also offered important contribution to a better understanding and development of therapeutic efficacy of anti-cancer drugs with reduced off-target effects. Cyclophosphamide (CP), an anti-cancer and immunosuppressant drug, causes fatal cardiotoxicity during high dose chemotherapy. Lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate possess a wide range of medicinal properties. Dr. Periyasamy-Thandavan evaluated the effect of lupeol and its ester in CP induced cardiotoxicity. His findings demonstrate that the supplementation with lupeol and its ester preserved membrane permeability, highlighting their protective effect against CP induced cardiotoxicity.

References: 1.Lieberthal W.Macroautophagy: a mechanism for mediating cell death or for promoting cell survival?Kidney Int. 2008 Sep;74(5):555-7