Sivakumar Viswanathan

Inhibition of an immunometabolic axis of mTORC1 activation extends mammalian healthspan

This study shows that inhibiting IL11 improves healthspan in aged mice by reversing metabolic dysfunction, sarcopenia, and frailty.

IL11 stimulates IL33 expression and proinflammatory fibroblast activation

This study shows IL11 promotes inflammation in fibroblasts by upregulating IL33 and other proinflammatory genes, with STAT3 signaling being critical for this effect.

IL11 stimulates ERK/P90RSK to inhibit LKB1/AMPK and activate mTOR in hepatocytes, the stroma and cancer cells

This study identifies IL11's role in inhibiting LKB1/AMPK and activating mTOR through ERK/P90RSK, leading to metabolic dysfunction and fibrosis in multiple cell types and NASH in mice.

Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis

This study compares IL11 and IL11RA1 knockout mice, finding IL11 deficiency protects against lung fibro-inflammation but causes infertility, while IL11RA1 deficiency leads to craniosynostosis.

Molecular dissection of pro-fibrotic signaling identifies the mechanism underlying IL11-driven fibrosis gene translation, reveals non-specific effects of STAT3 and suggests a new mechanism of action for nintedanib

The paper investigates IL11-driven fibrosis mechanisms, showing ERK, not STAT3, drives fibrogenesis and identifies a novel role for nintedanib in inhibiting pro-fibrotic translation.

Autocrine IL11 cis-signaling in hepatocytes is an initiating nexus between lipotoxicity and non-alcoholic steatohepatitis

The paper shows that autocrine IL11 signaling in hepatocytes drives lipotoxicity and NASH by causing lipoapoptosis and reactive oxygen species, with protection seen in Il11ra1-deleted mice.

Reliable detection of translational regulation with Ribo-seq

The paper introduces Xtail, a method to identify differentially translated genes by analyzing Ribo-seq data while accounting for mRNA abundance variations.

IL-11 is a therapeutic target in idiopathic pulmonary fibrosis

The paper identifies IL-11 as a therapeutic target in idiopathic pulmonary fibrosis by showing its role in fibroblast activation and fibrosis progression across species.

Translational control of cardiac fibrosis

The paper identifies translational regulators of fibrogenic genes in human cardiac fibroblasts and shows their role in cardiac fibrosis through ribosome profiling and RNA-binding protein analysis.

IL-11 neutralising therapies target hepatic stellate cell-induced liver inflammation and fibrosis in NASH

This study identifies IL-11 as a key driver of HSC-to-myofibroblast transformation in NASH, showing that targeting IL-11 reduces fibrosis and inflammation in preclinical models.