Approved Research

Clonal Hematopoiesis of Indeterminate Potential (CHIP) in Aging-Related Diseases and Inflammation: Genetic and Drug Repurposing Analyses for Therapeutic Target Prioritization

Lay summary

Clonal Hematopoiesis of Indeterminate Potential (CHIP) is the abnormal expansion of mutated blood cell lines without blood disease, and that is detectable as molecular signatures through techniques of genetic sequencing.

CHIP occurs with ageing, and is common. Importantly, CHIP is associated with elevated risks of aging-related diseases such as heart and vascular diseases, stroke, chronic lung disease, abnormal kidney function, as well as inflammatory conditions.

Therefore CHIP represents an important "submerged" clinical iceberg of under-studied health risk that is concealed at the population level. It therefore represents an important underlying cause of morbidities and death risk beyond the conventional risk factors in the ever ageing population.

While inflammation is implicated as an explanatory pathway to explain why CHIP increases the risk of aging-related diseases, the exact underlying scientific mechanisms of CHIP remained poorly understood.

Moreover, currently there is no preventive strategies yet to address the elevated risks of heart diseases and aging-related diseases associated with CHIP.

Therefore, there is a pressing need for further research to unravel the causal mechanistic pathways, and look for factors that can mitigate the disease risks associated with CHIP.

In this proposed research project over 36 months, we will comprehensively dissect the complex relations between CHIP and aging-related diseases through studies of genetic variants related to CHIP and related biological pathways, and studies of drugs and factors that might have the potentials to modulate and ameliorate the heath risks of CHIP. We believe this project will yield important insights in the mechanisms of CHIP leading to heart and aging-related diseases, and shield lights on future prevention strategies and inform therapeutic target prioritization.

The public health impact will be tremendous in terms of allow us to identify factors to abrogate the health risks of CHIP.