Inhye Park

Project: Functional investigation of a novel subset of vascular macrophages in cardiovascular health and disease

Research summary

My research interest lies in characterising vascular macrophage heterogeneity and exploiting macrophage functions to alleviate cardiovascular diseases (CVD). Tissue resident macrophages play a non-redundant role in organ function, immune responses, and reparative processes to ensure tissue homeostasis. My previous work was focused on understanding the protective mechanisms of vascular macrophages in atherosclerosis. Using single cell technologies, I have identified a novel vascular macrophage subset defined by the expression of a C-type lectin receptor. This subset is conserved across various organs and presents with unique features and a distinct transcriptomic profile.

My BHF CRE Fellowship project aims to investigate the role of this newly identified macrophage subset in acute and chronic heart failure. The work will identify the subtissular niche of this subset and its interplay with the cardiovascular system, which will define its role in myocardial infarction. The findings from this work will enable an improved mechanistic insight into the role of resident vascular macrophages that, ultimately, could be exploited for therapeutic application in CVD.

Background

I undertook my DPhil project in the laboratory of Prof. Claudia Monaco at the University of Oxford to investigate how a C-type lectin receptor CLEC4A2 directs macrophages towards a protective function in atherosclerosis. In 2021, I was awarded a Novo Nordisk Fellowship to identify key transcription factors that define tissue identity of resident vascular macrophages using in vitro and in vivo validation. The project aimed to identify target genes that were conserved in resident macrophages in human and mouse vascular tissues. Target validation was performed using a platform that combines vascular co-culture and CRISPR screens and functional studies in murine models of atherosclerosis.

To pursue my independent research, I applied for a BHF CRE Transition Fellowship to explore the role of a novel subset of vascular macrophages identified in my previous studies in acute and chronic heart failure models. This work will be supported by two leading experts in this field, Prof. Paul Riley (IDRM) in cardiovascular regenerative medicine and Prof. Claudia Monaco (Kennedy, NDORMS) in cardiovascular inflammation. Through this fellowship, I aim to build on my own research linking immunology and metabolism in macrophages in CVD and identifying therapeutic targets for translational application in the clinic.