Office : BRC1368A
Lab : BRC1372
975 NE 10th Street, BRC 1368A
Oklahoma City, OK 73104
Phone (Office) : 405-271-8001 (Extn:48393)
PhD University of Kerala, India
Post Doctoral Fellowships-Kobe Pharmaceutical University (Japan) and University of Cambridge (UK)
Inflammation and Aging, Necroptosis
Research in my lab focuses on characterizing the role of inflammation in aging and age-related diseases. Chronic, low-grade inflammation (inflammaging) is a hallmark of aging and age-associated diseases such as cancer, type 2 diabetes, Alzheimer’s disease etc. Our current studies aims to identify the molecular pathways responsible for inflammaging and to determine if inflammation is a causative factor in aging and age-associated diseases. Necroptosis (programmed necrosis) is a novel cell death pathway that plays a major role in inflammation, however, little is known about the role of necroptosis in the age-related increase in chronic inflammation or aging. Using genetic and pharmacological approaches to block/reduce necroptosis in mice, we are studying the role of necroptosis-induced inflammation on lifespan and healthspan of mice.
We are also studying the role of necroptosis-mediated inflammation in a mouse model of accelerated aging, mice deficient in CuZnSOD (Sod1-/- mice). Sod1-/- mice is characterized by high levels of oxidative stress, increased levels of circulating proinflammatory cytokines, and increased necroptosis. Using genetic manipulations to block necroptosis in Sod1-/- mice, we are determining the effect of necroptosis-mediated inflammation on healthspan (cognition, rota-rod performance, metabolic measures etc.). We have also developed a mouse model that is deficient in CuZnSOD in adipose tissue, to determine the role of adipose tissue in systemic inflammation.
Sod1-/- mice show increased incidence of hepatocellular carcinoma (HCC, an example of inflammation-related cancer) with age. Sod1-/- mice also exhibit a fatty liver phenotype and liver cirrhosis that are associated with the development of HCC. We have found that blocking necroptosis reduces inflammation in Sod1-/- mice liver. Future studies will focus on understanding the role of necroptosis in HCC.
- Deepa SS, Van Remmen H, Brooks SV, Faulkner JA, Larkin L, McArdle A, Jackson MJ, Vasilaki A, Richardson A. Accelerated sarcopenia in Cu/Zn superoxide dismutase knockout mice. Free Radic Biol Med. 2019 Feb 20;132:19-23. doi: 10.1016/j.freeradbiomed.2018.06.032. Epub 2018 Jul 2. Review. PubMed PMID: 30670156; PubMed Central PMCID: PMC6405207.
- Deepa SS, Pharaoh G, Kinter M, Diaz V, Fok WC, Riddle K, Pulliam D, Hill S, Fischer KE, Soto V, Georgescu C, Wren JD, Viscomi C, Richardson A, Van Remmen H. Lifelong reduction in complex IV induces tissue-specific metabolic effects but does not reduce lifespan or healthspan in mice. Aging Cell. 2018 Apr 25;:e12769. doi: 10.1111/acel.12769. [Epub ahead of print] PubMed PMID: 29696791; PubMed Central PMCID: PMC6052393.
- Deepa SS, Unnikrishnan A, Matyi S, Hadad N, Richardson A. Necroptosis increases with age and is reduced by dietary restriction. Aging Cell. 2018 Apr 25;:e12770. doi: 10.1111/acel.12770. [Epub ahead of print] PubMed PMID: 29696779; PubMed Central PMCID: PMC6052392.
- Snider TA, Richardson A, Stoner JA, Deepa SS. The Geropathology Grading Platform demonstrates that mice null for Cu/Zn-superoxide dismutase show accelerated biological aging. Geroscience. 2018 Apr;40(2):97-103. doi: 10.1007/s11357-018-0008-0. Epub 2018 Feb 24. PubMed PMID: 29478190; PubMed Central PMCID: PMC5964058.
- Bhaskaran S, Pharaoh G, Ranjit R, Murphy A, Matsuzaki S, Nair BC, Forbes B, Gispert S, Auburger G, Humphries KM, Kinter M, Griffin TM, Deepa SS. Loss of mitochondrial protease ClpP protects mice from diet-induced obesity and insulin resistance. EMBO Rep. 2018 Mar;19(3). doi: 10.15252/embr.201745009. Epub 2018 Feb 2. PubMed PMID: 29420235; PubMed Central PMCID: PMC5836096.
- Bhaskaran S, Unnikrishnan A, Ranjit R, Qaisar R, Pharaoh G, Matyi S, Kinter M, Deepa SS. A fish oil diet induces mitochondrial uncoupling and mitochondrial unfolded protein response in epididymal white adipose tissue of mice.Free Radic Biol Med. 2017 Jul;108:704-714. doi: 10.1016/j.freeradbiomed.2017.04.028. Epub 2017 Apr 26. PubMed PMID: 28455142.
- Deepa SS, Bhaskaran S, Espinoza S, Brooks SV, McArdle A, Jackson MJ, Van Remmen H, Richardson A. A new mouse model of frailty: the Cu/Zn superoxide dismutase knockout mouse. Geroscience. 2017 Apr;39(2):187-198. doi: 10.1007/s11357-017-9975-9. Epub 2017 Apr 13. PubMed PMID: 28409332; PubMed Central PMCID: PMC5411367.
- Zhang Y, Unnikrishnan A, Deepa SS, Liu Y, Li Y, Ikeno Y, Sosnowska D, Van Remmen H, Richardson A. A new role for oxidative stress in aging: The accelerated aging phenotype in Sod1-/- mice is correlated to increased cellular senescence.Redox Biol. 2017 Apr;11:30-37. doi: 10.1016/j.redox.2016.10.014. Epub 2016 Nov 2. PubMed PMID: 27846439; PubMed Central PMCID: PMC5109248.
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