Research Interests
Molecular Mechanisms of Energy Balance
Our research program is dedicated to exploring mechanisms linking obesity with cardiometabolic complications. These include the molecular mechanisms that control energy expenditure, fat deposition, and the partitioning of energy towards oxidation or storage, with a particular focus on how these processes are disrupted in obesity. Our work addresses the following interrelated questions:
Adipose Tissue Dysfunction and Lipotoxicity: We investigate how dysfunction in adipose tissue, especially in white adipose tissue (WAT), leads to lipotoxicity—a condition where ectopic fat accumulation in non-adipose tissues (like liver, muscle, and pancreas) induces cellular injury, inflammation, and insulin resistance. By examining the mechanisms that cause adipose tissue to fail in safely storing lipids, we aim to identify how this dysfunction contributes to the development of metabolic-associated steatotic liver disease (MASLD) and other complications of metabolic syndrome.
Brown Fat Biology as an Anti-Lipotoxic Strategy: Recognising the protective role of brown adipose tissue (BAT) in energy expenditure and thermogenesis, our research explores the activation of BAT and the browning of WAT (conversion to beige adipocytes) as strategies to counteract lipotoxicity. By enhancing lipid oxidation in these thermogenic tissues, we aim to reduce ectopic fat deposition and alleviate the associated metabolic burden. Our studies focus on understanding the molecular signals that regulate BAT activity and beige adipocyte formation, with the goal of developing therapeutic interventions that leverage these pathways to prevent or reverse lipotoxicity.
Nutrient Partitioning and Energy Metabolism: Our research also focuses on how modulating nutrient partitioning can prevent the adverse effects of excess fat storage. We investigate mechanisms that promote fatty acid oxidation in skeletal muscle and reduce lipid accumulation in adipose tissue, aiming to redirect energy utilisation in ways that support metabolic health and combat obesity.
MASLD as a Manifestation of Lipotoxicity: MASLD represents a critical manifestation of lipotoxicity, characterised by ectopic fat deposition in the liver, which can progress to inflammation, fibrosis, and further complications. Our framework integrates the study of how cellular injury, inflammation, and fibrosis are coupled in the context of lipotoxicity. By dissecting these pathways, we hope to elucidate the links between adipose tissue dysfunction, systemic metabolic disturbances, and organ-specific pathologies like MASLD.
To address these complex challenges, our laboratory employs an Integrated Physiology approach, utilising genetically modified models to unravel the intricacies of energy homeostasis. We complement this with Systems Biology methods, including transcriptomic, lipidomic, and bioinformatic analyses, to map lipid metabolic networks across different organs and understand their relevance to insulin resistance and metabolic disease. Our ultimate goal is to identify novel biomarkers and therapeutic targets that can inform precision medicine approaches for treating obesity and its associated metabolic disorders.
Group Members
Dr Vanesa Bernal, Visiting Researcher
Dr Guillaume Bidault, Post Doctoral Research Associate - gb483 at medschl.cam.ac.uk
Mr Mark Campbell, Scientific and Operational Excellence Manager - mjc97 at medschl.cam.ac.uk
Dr Stefania Carobbio, Visiting Scientist - sc547 at medschl.cam.ac.uk
Miss Petra Chen - MPhil Student - ztc22 at cam.ac.uk
Mr Martin Dale, Research Assistant - md215 at medschl.cam.ac.uk
Miss Rita Dias, PhD Student - ard68 at medschl.cam.ac.uk
Miss Ruoqi Du, PhD Student - rd658 at medschl.cam.ac.uk
Mrs Katie Fisher - PA - klk30 at medschl.cam.ac.uk
Dr Isabel Fuster Martinez, Postdoctoral Research Associate - if293 at cam.ac.uk
Dr Ioannis Kamzolas, Postdoctoral Research Associate - ik352 at medschl.cam.ac.uk
Professor Eunyoung Lee, Visiting Researcher - el496 at cam.ac.uk
Mr Iman Mali, PhD Student/Research Assistant - im483 at medschl.cam.ac.uk
Dr Vanessa Pellegrinelli, Post Doctoral Research Associate - vp332 at medschl.cam.ac.uk
Mr Possawee Prasertsuk, PhD Student - pp538 at medschl.cam.ac.uk
Dr Sergio Rodriguez-Cuenca, Senior Research Associate - sr441 at medschl.cam.ac.uk
Dr Sonia Rodriguez-Fernandez, Postdoctoral Fellow - sr942 at medschl.cam.ac.uk
Miss Taylor Simonian, MPhil Student - ts953 at cam.ac.uk
Mr Harry Weston, PhD Student - hnw25 at cam.ac.uk
