Constantinos Christodoulides

My research investigates how obesity drives the development of type 2 diabetes and coronary heart disease. Specifically, it focuses on uncovering the molecular determinants of adipocyte number and distribution - key factors underlying susceptibility to obesity-related cardiometabolic diseases - with the aim of translating these insights into novel therapeutic strategies. To achieve this, we adopt a multidisciplinary approach, integrating human genetic and physiological studies with functional experiments in human adipose cells, Mendelian randomisation analyses, and drug screening. Previously, we identified WNT pathway molecules, LRP5 and RSPO3, as novel regulators of human fat distribution. Notably, LRP5 is already a therapeutic target for osteoporosis, underscoring the translational potential of this work. Currently, my research also explores additional developmental signaling pathways, such as TGF-beta signaling, which genetic evidence suggests play a critical role in modulating fat distribution and influencing the risk of type 2 diabetes and coronary heart disease.

LRP5 promotes adipose progenitor cell fitness and adipocyte insulin sensitivity. Loh NY. et al, (2025), Commun Med (Lond), 5 Multiomic Mendelian Randomization Study Investigating the Impact of PCSK9 and HMGCR Inhibition on Type 2 Diabetes Across Five Populations. Rosoff DB. et al, (2025), Diabetes, 74, 120 - 130 Bidirectional Mendelian Randomization Highlights Causal Relationships Between Circulating INHBC and Multiple Cardiometabolic Diseases and Traits. Loh NY. et al, (2024), Diabetes, 73, 2084 - 2094 Investigating the impact of metabolic syndrome traits on telomere length: a Mendelian randomization study. Loh NY. et al, (2023), Obesity (Silver Spring), 31, 2189 - 2198 Metabolic Syndrome traits and telomere length: a Mendelian Randomization study. LOH N. et al, (2023), Obesity