I have shown that High Mobility Group Box 1 protein (HMGB1), a chromatin protein, is the main signal that distressed or prematurely dead cells release to activate the immune system. Indeed, since HMGB1 exists since the appearance of eukaryotes, the immune system essentially evolved around HMGB1, and progressively acquired layer upon layer of sophistication. In our body, HMGB1 remains the cornerstone of the response to assaults on integrity, including physical injury or infection. I have shown that HMGB1 triggers inflammation, recruits and activates inflammatory cells, is an adjuvant in eliciting adaptive immunity, and promotes healing after damage. Because of its central role, HMGB1 is involved in most medical conditions.

My current vision is that HMGB1 can be either muted when the systemic response to infection or injury is excessive (for example in sepsis, or in the so-called “cytokine storm”), or leveraged to promote healing. Recently, we have found that a fragment of HMGB1 can promote the internalization of the receptor CXCR4 and the “don’t eat me” molecule CD47 from the surface of cells, leading to macrophage phagocytosis and the emergence of anti-tumor CD8 T cell clones that lead to tumor rejection in a large fraction of tumor-bearing mice. My current motivation is to exploit medical uses of HMGB1. I have founded the biotech company HMGBiotech, which has developed a neutralizing monoclonal antibody against HMGB1 and a designer potentiated version of HMGB1, called 3S; several peptide and small molecule inhibitors or mimics of HMGB1 are in the development.