Heme metabolism and Heme oxygenase-1

Heme is an iron-containing porphyrin and a prosthetic group for the activity of many hemoproteins participating in core cellular function. It is best known for its indispensable role for oxygen transport in hemoglobin. However, when released into the circulation upon cellular damage, this “labile” heme becomes cytotoxic and can promote tissue dysfunction and damage. As such it is sensed as an alarmin by cells of the innate immune system via Toll-like Receptor-4 and the C-type lectin CLEC-2. In our group we study heme/iron metabolism on the cellular and organismal level and heme degradation by Heme oxygenase-1. Recently we could show that exposure of low-levels of heme induce innate immune training and that heme is a previously unrecognized effector of hematopoietic lineage specification inducing a specific myeloid Multipotential Progenitor (MPP) cell population.

Currently we are investigating the role of the Heme oxgenase-1 in metabolic adaptation to heme. Other projects investigate early signal transduction events in heme-signaling and their role on of the redox-active central iron atom for heme-signaling.

Five most important publications

Lin Q, Weis S, Yang G, Weng YH, Helston R, Rish K, Smith A, Bordner J, Polte T, Gaunitz F, Dennery PA (2007) Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress. J Biol Chem 282(28), 20621-33.

Weis S, Carlos AR, Moita MR, Singh S, Blankenhaus B, Cardoso S, Larsen R, Rebelo S, Schäuble S, Del Barrio L, Mithieux G, Rajas F, Lindig S, Bauer M, Soares MP (2017) Metabolic adaptation establishes disease tolerance to sepsis. Cell 169(7), 1263-75 e14.

Blankenhaus B, Braza F, Martins R, Bastos-Amador P, González-García I, Carlos AR, Mahu I, Faisca P, Nunes JM, Ventura P, Hoerr V, Weis S, Guerra J, Cardoso S, Domingos A, López M, Soares MP (2019) Ferritin regulates organismal energy balance and thermogenesis. Mol Metab 24, 64-79.

Jentho E, Ruiz-Moreno C, Novakovic B, Kourtzelis I, Megchelenbrink WL, Martins R, Chavakis T, Soares MP, Kalafati L, Guerra J, Roestel F, Bohm P, Godmann M, Grinenko T, Eugster A, Beretta M, Joosten LAB, Netea MG, Bauer M, Stunnenberg HG, Weis S (2021) Trained innate immunity, long-lasting epigenetic modulation, and skewed myelopoiesis by heme. Proc Natl Acad Sci U S A 118(42).

Jentho E, Weis S (2021) DAMPs and innate immune training. Front Immunol, accepted.