Sathyaseelan Lab

Deepa Sathyaseelan, PhD
Associate Professor

Lab focus

The Sathyaseelan lab investigates how aging alters the necroptosis effector MLKL and its regulation of inflammation and mitochondrial dysfunction, two key pillars of aging. We aim to determine how these processes drive organ and systemic decline and whether targeting them can extend healthspan.

Key research areas:

Liver-Brain axis and cognitive decline– We study how chronic liver inflammation and liver diseases drive neuroinflammation and cognitive decline during aging. By examining how cytokines and extracellular vesicles mediate liver-to-brain communication, we aim to uncover mechanisms through which peripheral signals regulate age-associated cognitive decline and identify strategies to preserve brain health in aging
Necroptosis and Inflammaging– Chronic, low-grade inflammation (inflammaging) is a hallmark of aging. We discovered that inhibiting MLKL reduces inflammation in multiple organs, including the liver, brain, and kidney, in aged mice. To understand the role of cell-type specific necroptosis in inflammaging, we are using novel mouse models to dissect its role in tissue parenchymal cells (hepatocytes, adipocytes, neurons) and non-parenchymal immune cells (macrophages, microglia). Understanding the cell-type-specific role of necroptosis will reveal how distinct cell populations sustain chronic inflammation during aging and identify precise molecular targets to interrupt this process.
MLKL at the crossroads of aging and cancer: A Gerooncology perspective– Aging is the biggest risk factor for several cancers, including hepatocellular carcinoma (HCC), the primary form of liver cancer. Our studies show that aging increases hepatic MLKL expression and that inhibiting MLKL reduces HCC incidence in preclinical models, suggesting that MLKL serves as a molecular bridge linking aging and cancer. We are uncovering how MLKL promotes tumorigenesis through chronic inflammation, mitochondrial dysfunction, and non-necroptotic signaling, providing a geroonncology-focused framework to understand how age-related molecular pathways predispose to cancer.

Why it matters

Aging is the leading risk factor for chronic diseases such as fatty liver disease, neurodegeneration, and cancer, yet the molecular mechanisms linking aging to inflammation and organ decline remain poorly understood. Our research uncovers how dysregulation of the necroptosis effector MLKL contributes to these age-associated pathologies by promoting chronic inflammation and mitochondrial dysfunction. By defining cell-type specific and non-necroptotic roles of MLKL, we aim to identify therapeutic strategies that selectively suppress inflammatory signaling without impairing normal cell survival. Ultimately, this work seeks to translate basic discoveries into interventions that preserve metabolic and cognitive health and extend healthspan.

Faculty Bio

Deepa Sathyaseelan, PhD

Associate Professor
Department of Biochemistry and Physiology
Member, Stephenson Cancer Center
Member, Center for Geroscience and Healthy Brain Aging
Member, Harold Hamm Diabetes Center

Ph.D. Biochemistry, University of Kerala, India
Postdoctoral fellowships: Kobe Pharmaceutical University, Japan; University of Cambridge, UK

Honors, Recognition, Awards

NCI-funded Transdisciplinary Research on Energetics and Cancer (TREC) trainee, 2023
Stepheson Cancer Research Nominee for Pew-Stewart Scholar Program for Cancer Research, 2020
Junior faculty Travel award (American Aging Association), 2019
Trainee at Summer Training in Aging (Seattle, Washington), 2014

Publications

Mohammed S, Jiang C, Pennington T, Bhaskaran S, Ohene-Marfo P, Georgescu C, Pitts K, Tran A, Peng Z, Singh A, Yang Z, Li T, Hannafon B, Houchen C, Wren JD, Galvan V, Ahsan N, Kinter M, Lewis TL, Deepa SS. A Non-canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver. bioRxiv [Preprint]. 2025 May 3:2025.05.02.651782. PMID: 40654837.

Mohammed S, Ohene-Marfo P, Jiang C, Peng Z, Thadathil N, Tran A, Nicklas E, Bhaskaran S, Wang D, Selvarani R, Singh A, Yang Z, Ahsan N, Deepa SS. Impact of Mlkl or Ripk3 deletion on age-associated liver inflammation, metabolic health, and lifespan. Geroscience. 2025 Jun;47(3):4465-4483. PMID: 39930289.

Ohene-Marfo P, Nguyen HVM, Mohammed S, Thadathil N, Tran A, Nicklas EH, Wang D, Selvarani R, Farriester JW, Varshney R, Kinter M, Richardson A, Rudolph MC, Deepa SS. Non-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High-Fat, High-Fructose, High-Cholesterol Diet Mouse Model. Int J Mol Sci. 2024 Feb 28;25(5):2813. PMID: 38474061.

Mohammed S, Thadathil N, Ohene-Marfo P, Tran AL, Van Der Veldt M, Georgescu C, Oh S, Nicklas EH, Wang D, Haritha NH, Luo W, Janknecht R, Miller BF, Wren JD, Freeman WM, Deepa SS. Absence of Either Ripk3 or Mlkl Reduces Incidence of Hepatocellular Carcinoma Independent of Liver Fibrosis. Mol Cancer Res. 2023 Sep 1;21(9):933-946. PMID: 37204757.

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. PMID: 34761505.

Current Funding

NIH/NIA 2R01AG059718 (Role: PI, 7/1/2024-6/30/2029): The role of hepatocyte necroptosis and inflammation in liver-brain crosstalk in aging.

Harold Hamm Diabetes Center-Stepheson Cancer Center Team Science Grant (Role: PI, 7/1/2024-6/30/2027): The Role of Hepatocyte MLKL in Type 2 Diabetes Mellitus-Associated Hepatocellular Carcinoma.

Oklahoma Center for Adult Stem Cell Research Grant Role: PI, 7/1/2024-6/30/2025): The role of hepatocyte MLKL on cancer stemlike cells in hepatocellular carcinoma.

NIH/NIA R01AG059718 (Role: PI, 5/1/2019-4/30/2024, no cost extension till Feb 2025): The role of necroptosis in aging.

NIH/NCI R03 CA262044-1A1 (Role: PI, 03/01/2022-02/28/2024). Understanding the role of necroptosis in hepatocellular carcinoma.