Our research focus...

The laboratory of Dr. Peter R. Hoffmann is located at the John A. Burns School of Medicine, University of Hawai`i, Honolulu, Hawai`i. Our research interests include, but are not limited to, the role of selenium and selenoproteins in immunity; calpains/calpastatin in regulating inflammation. Also, Dr. Bertino has initiated several novel and exciting projects related to cancer therapy.

    We have long been interested in revealing mechanisms by which dietary selenium influences inflammation and immunity. Our studies have shown that levels of selenium intake change the redox status of immune cells and this dramatically affects their activation, proliferation, differentiation, and function. In addition to redox status, changes in selenium status can directly affect expression levels of individual selenoproteins in a wide variety of immune cells. There are 25 human selenoproteins, 24 of which exist as selenoproteins in mice. We recently identified selenoprotein K (Selk) as an endoplasmic reticulum membrane protein enriched in immune cells that functions to promote receptor-mediated calcium flux during immune cell activation. A number of our recent publications have demonstrated how Selk-deficiency alters cellular signaling and functions of immune cells including T cells, macrophages, neutrophils, and others. Collectively, Selk-deficiency leads to impaired immune responses to viruses and pathogen associated molecules, but also decreases immune driven disorders such as atherosclerosis. We are currently dissecting the molecular interactions of Selk with other cellular proteins and the precise biochemical mechanisms by which Selk regulates immune cell function. We also discovered that Selk is regulated by calpain cleavage, which led us to expand our investigations to include the calpain enzymes and the endogenous inhibitors of their activity, calpastatin. Our work has revealed a critical role of calpastatin as a master regulator macrophage activation and limiting inflammatory disorders such as colitis.