Grants Awarded

Principal Investigator:
Tamir Diamond
Children’s Hospital of Philadelphia,
Philadelphia, PA USA

Date of Award:
December 2025

Amount of Award:
51,000
(Founder’s Grant and Toughill Prize)

Layperson Summary:
This project’s goal is to improve care for children suffering from hemophagocytic lymphohistiocytosis (HLH) liver failure. This is a common cause of acute liver failure in children under the age of 2. One of the main mediators of disease in HLH is a small protein called interferon gamma (IFNg). IFNg helps clear viruses and protect you from cancer at normal levels. However, when levels are too high, as in HLH, it can cause a patient to be very sick. We know that the liver in HLH responds strongly to IFNg and that in mice IFNg causes injury to the lining of the little blood vessels in the liver called liver sinusoidal endothelial cells (LSEC). However, we don’t know entirely why the LSEC get injured and how this cell type contributes to liver failure. In this project we will start answering this question by using a mouse model of HLH that has LSEC that don’t respond to IFNg. We will do experiments studying how this may protect mice from liver injury but also how the LSEC interact with the immune cells using a new technology call spatial transcriptomics. These experiments will help us understand the role of LSEC response to IFNg. With that information we may be able to choose drugs that may be helpful for patients with HLH liver failure to prevent their need for liver transplant.