Office : BRC1368B
Lab : BRC1370
975 NE 10th Street, BRC 1368B
Oklahoma City, OK 73104
Phone (Office) : 405-271-8001 (Ext: 48393)
PhD University of Kerala, India
Post Doctoral Fellowships-Kobe Pharmaceutical University (Japan) and University of Cambridge (UK)
Inflammation, Necroptosis, Aging, Non-Alcoholic Fatty Liver Disease (NAFLD), Hepatocellular carcinoma (HCC), and Obesity
Chronic inflammation and aging. Our research is focused on identifying the molecular pathways responsible for inflammaging, which is characterized by a chronic, low-grade inflammation that is commonly associated with aging and age-related diseases. While a new cell death pathway called necroptosis has been shown to play a role in chronic inflammation, its involvement in aging and age-related inflammation is not yet fully understood. Our research has revealed that necroptosis increases with age in multiple tissues of mice and that inhibiting this pathway reduces tissue inflammation and cellular senescence, which is a significant factor in the development of inflammaging. Our current studies are aimed at investigating the role of necroptosis in liver inflammation and its influence on the onset of chronic liver diseases, as well as its role in neuroinflammation and the aging of the brain.
The role of necroptosis in NAFLD and HCC. Metabolic syndrome, which includes obesity, diabetes, and dyslipidemia, is responsible for the development of NAFLD in almost 25% of the US population. NAFLD poses a significant risk for the development of HCC, and in the United States, NAFLD-related HCC has become the primary cause of HCC among liver transplant candidates, particularly in the elderly. However, the mechanisms that contribute to the development of HCC in NAFLD are not fully understood. The progression of NAFLD to HCC is significantly influenced by chronic inflammation that remains unresolved. Necroptosis, an inflammatory mode of cell death, is elevated in the livers of both patients and mouse models of NAFLD. To gain insight into the role of necroptosis-induced inflammation in the development of HCC associated with obesity and aging, we are utilizing novel genetic mouse models and pharmacological methods to target the necroptosis pathway.
- Thadathil N, Selvarani R, Mohammed S, Nicklas EH, Tran AL, Kamal M, Luo W, Brown JL, Lawrence MM, Borowik AK, Miller BF, Van Remmen H, Richardson A, Deepa SS. Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma. Aging Cell. 2022 Aug;21(8):e13676. PMCID: PMC9381894.
- Swetha M, Keerthana CK, Rayginia TP, Nath LR, Haritha NH, Shabna A, Kalimuthu K, Thangarasu AK, Aiswarya SU, Jannet S, Pillai S, Harikumar KB, Sundaram S, Anto NP, Wu DH, Lankalapalli RS, Towner R, Isakov N, Deepa SS, Anto RJ. Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma. Pharmaceuticals (Basel). 2022 May 22;15(5):636. PMCID: PMC9143354.
- Mohammed S, Thadathil N, Selvarani R, Nicklas EH, Wang D, Miller BF, Richardson A, Deepa SS. Necroptosis contributes to chronic inflammation and fibrosis in aging liver. Aging Cell. 2021 Dec;20(12):e13512. PMCID: PMC8672775.
- Thadathil N, Nicklas EH, Mohammed S, Lewis TL Jr, Richardson A, Deepa SS. Necroptosis increases with age in the brain and contributes to age-related neuroinflammation. Geroscience. 2021 Oct;43(5):2345-2361. PMCID: PMC8599532.
- Mohammed S, Nicklas EH, Thadathil N, Selvarani R, Royce GH, Kinter M, Richardson A, Deepa SS. Role of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress. Free Radic Biol Med. 2021 Feb 20;164:315-328. PMID: 33429022; PMCID: PMC8845573.
- Royce GH, Brown-Borg HM, Deepa SS. The potential role of necroptosis in inflammaging and aging. Geroscience. 2019 Dec;41(6):795-811. PMCID: PMC6925091.
- Logan S, Royce GH, Owen D, Farley J, Ranjo-Bishop M, Sonntag WE, Deepa SS. Accelerated decline in cognition in a mouse model of increased oxidative stress. Geroscience. 2019 Oct;41(5):591-607. PMCID: PMC6885085.
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