Grants Awarded

Principal Investigator:
Polina Shindiapina
The Ohio State University,
Ohio, USA

Date of Award: 
December 2025

Amount of Award:
50,000

Layperson Summary:
Hemophagocytic lymphohistiocytosis/macrophage activation syndrome, also known as HLH/MAS, is a rare but often fatal disease in adults. Normally, our immune system responds to infections or to cancer by killing the offending infection or destroying cancer cells. In HLH/MAS, the immune response to a stimulus such as infection or cancer does not work correctly and becomes overwhelming. This overwhelming immune activation can lead to organ damage and even death. Currently we do not have many effective therapies to treat HLH, and up to one half of adult patients with HLH can die despite treatment with approved therapies. Therefore, the discovery of new therapies is urgently needed.

The bromodomain and extra terminal domain (BET) proteins have emerged as regulators of inflammation and immune responses. Dr. Shindiapina and Dr. Ranganathan at the Ohio State University performed preliminary experiments that suggested that selective inhibition of BET activity in the mouse model of secondary HLH/MAS appeared effective in treating the disease. We propose to validate these results and to study the function of BET activity in the mouse model of HLH/MAS in more detail. BET inhibitors have been tested and well tolerated in human clinical trials treating patients with cancer and inflammation of graft-versus-host disease. We hope that the data acquired in the experiments described in this proposal will lead us to perform clinical trials of drugs that block BET activity and may therefore treat human patients with HLH.