Metabolism

This research theme explores cellular metabolism in cancer and immune-related cells, spanning mitochondrial function, nutrient adaptation, and responses to stress. Professor Daniel Tennant’s research team investigates how cells, adapt to oxygen-limited environments (hypoxia) and how these adaptations effect hypoxic cells, such as tumour cells. Prof. Tennant also leads the Metabolic Tracer Analysis Core (MTAC) facility. Research in Dr. Sarah Dimeloe’s lab is focused on the metabolism of immune cells and how this underpins their role in health and disease. Dr Christian Ludwig develops and applies advanced metabolic tracer technologies to quantify metabolic flux and pathway usage in human health and disease.

Selected publications 

• Bachoo S, Gudgeon N, Mann R, Stavrou V, Bishop EL, Kelly A, Uribe AH, Loeliger J, Frick C, Maddocks ODK, Lavender P, Hess C & Dimeloe S (2025). IL-7 promotes integrated glucose and amino acid sensing during homeostatic CD4+ T cell proliferation. Cell Reports, 44(1):115199
• Ludwig C (2025). MetaboLabPy: An Open-Source Software Package for Metabolomics NMR Data Processing and Metabolic Tracer Data Analysis. Metabolites, 15(1):48
• Bishop EL, Gudgeon N, Fulton-Ward T, Stavrou V, Roberts J, Boufersaoui A, Tennant DA, Hewison M, Raza K, Dimeloe S (2024). TNF-α signals through ITK-Akt-mTOR to drive CD4+ T cell metabolic reprogramming, which is dysregulated in rheumatoid arthritis. Sci Signal, 17(833):eadg5678
• Westbrook RL, et al. (2022). Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. Cell Reports, 38(5):110320
• Clayton SA, et al. (2021). Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48. Science Advances, 7(50):eabl5182

In the diabetes sub-theme, Dr Ildem Akerman and Dr Gabriela da Silva Xavier investigate insulin secretion and β-cell function. Dr. Xavier is also a member of NIHR BRC Women’s Metabolic Health Theme. Dr Akerman's group uses genomics and stem-cell derived beta cell (SC-islet) models to understand the transcriptional networks that govern β-cell identity, with the goal of producing better in vitro models and regenerative therapies for Type 1 diabetes. Her recent work also includes GPCR signalling in stem-cell-derived β-cells, as well as chromatin and DNA replication dynamics that affect β-cell maturity and stress responses.

Dr. Akerman is also the lead for BetaCell Birmingham, an academic facility that produces stem cell-derived beta cells for UK researchers. Dr da Silva Xavier’s research focuses on metabolic flexibility in pancreatic islets - particularly how nutrient sensing is altered in obesity-linked diabetes and rare monogenic forms. Dr da Silva Xavier and Professor Tarekegn Hiwot collaborate in the area of rare metabolic conditions such as Alström Syndrome and Acromegaly, where β-cell function and/or insulin sensitivity are impaired as a result of metabolic dysfunction. Their work is highly translational, with a strong focus on understanding how metabolic dysfunction arises and how it might be reversed using dietary, pharmacological, or cell-based interventions.

Dr Sofia Ahola examines molecular mechanisms that underlie mitochondrial diseases and the ensuing stress responses to mitochondrial dysfunction and metabolism.

Dr Maria Makarova studies the core principles of metabolic regulation using yeast as a model organism, to determine how cells adjust membrane composition and structure under metabolic stress.

Dr. Rowan Hardy, co-based in the Department of Biomedical Sciences and our department, further contributes to the theme by investigating how steroid metabolism regulates inflammation and its effects on muscle and bone, aiming to develop safer glucocorticoid therapies through interdisciplinary collaboration. 

Selected publications

• Crastin A, Shanker A, Sagmeister MS, Taylor A, Lavery GG, Raza K & Hardy RS (2025). Vamorolone: a novel metabolism resistant steroid that suppresses joint destruction in chronic polyarthritis with reduced systemic side effects. Rheumatology, 64(7):4371–4381
• Ali S, Heising S, Veeranna V, et al. (2024). Disrupted Mitochondrial Function in Alström Syndrome—A Monogenic Model of Insulin Resistance and Obesity. Journal of the Endocrine Society, 8(Supplement_1):bvae163.738
• Ali S, Baig S, Wanninayake S, et al. (2024). Glucagon-like peptide-1 analogues in monogenic syndromic obesity: Real-world data from a large cohort of Alström syndrome patients. Diabetes, Obesity and Metabolism, 26(3):989–996
• Ahola S, et al. (2024). Opa1 processing is dispensable in mouse development but is protective in mitochondrial cardiomyopathy. Science Advances, 10(31):eadp0443
• Panconi L, et al. (2024). Mapping membrane biophysical nano-environments. Nature Communications, 15(1):9641
• Thomas P, Gallagher MT, da Silva Xavier G, et al. (2023). Beta cell lipotoxicity in the development of type 2 diabetes: the need for species-specific understanding. Frontiers in Endocrinology, 14:1275835
• Panconi L, et al. (2023). Phospholipid tail asymmetry allows cellular adaptation to anoxic environments. Journal of Biological Chemistry, 299(9):105134
• Ahola S, et al. (2022). OMA1-mediated integrated stress response protects against ferroptosis in mitochondrial cardiomyopathy. Cell Metabolism, 34(11):1875–1891.e7
• Akerman I, Maestro MA, De Franco E, et al. (2021). Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene. Cell Reports, 35(2):108981
• Nguyen-Tu MS, Martinez-Sanchez A, Leclerc I, et al. (2021). Adipocyte-specific deletion of Tcf7l2 induces dysregulated lipid metabolism and impairs glucose tolerance in mice. Diabetologia, 64:129–141
• Akerman I, Tu Z, Beucher A, et al. (2017). Human pancreatic β cell lncRNAs control cell-specific regulatory networks. Cell Metabolism, 25(2):400–411

The Metabolic Receptor Biology subtheme aims to investigate the fundamental mechanisms of G protein-coupled receptor (GPCR) signalling and their alterations in metabolic and endocrine disease. A key focus ofProfessor Davide Calebiro’s lab is the development of innovative microscopy methods (such as FRET and single-molecule microscopy), in combination with new biosensors, to monitor receptor signalling directly in living cells and tissues with unprecedented spatiotemporal resolution. This is combined with novel mathematical and computational approaches to extract information from complex imaging data and model receptor signalling at both molecular and cellular level.

Using this multi-disciplinary approach, the Calebiro team has redefined fundamental mechanisms of GPCR signalling, including the discovery that GPCRs are not only active at the plasma membrane, but also at intracellular sites such as endosomes and the Golgi complex.

Dr. Caroline Gorvin’s team have identified genetic alterations in GPCR signalling as drivers of endocrine and metabolic disease. The Calebiro and Gorvin teams are investigating novel GPCR targets for the therapy of metabolic diseases. Prof. Calebiro is also Co-Director of COMPARE, a joint Research Centre with the University of Nottingham aimed at elucidating the fundamental mechanisms of receptor signalling in physiology and disease to develop innovative therapies.

Selected publications 

• Wallis NJ, McClellan A, Mörseburg A, et al. (2025). Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans. Science, 387(6741):eads2145
• Wyatt RA, Gallagher MT, Zha L, et al. (2025). A calcium-sensing receptor dileucine motif directs internalization to spatially distinct endosomal signaling pathways. iScience, 28(6)
• Lovegrove CE, Goldsworthy M, Haley J, et al. (2025). Genetic variants predisposing to increased risk of kidney stone disease. The Journal of Clinical Investigation
• Price ML, Wyatt RA, Correia J, et al. (2025). Identification of anti-resorptive GPCRs by high-content imaging in human osteoclasts. Journal of Molecular Endocrinology, 74(4)
• Guillou A, Kemkem Y, Lafont C, et al. (2024). Thyroid-stimulating hormone pulses finely tune thyroid hormone release and TSH receptor transduction. Endocrinology, 165(1):bqad164
• Grimes J, Koszegi Z, Lanoiselée Y, et al. (2023). Plasma membrane preassociation drives β-arrestin coupling to receptors and activation. Cell, 186(10):2238–2255.e20
• Jobin ML, Siddig S, Koszegi Z, et al. (2023). Filamin A organizes γ-aminobutyric acid type B receptors at the plasma membrane. Nature Communications, 14(1):34
• O’Brien SL, Tripp E, Barki N, Blondel-Tepaz E, Smith G, Boufersaoui A, Roberts J, Pike JA, Correia J, Miljus T, Bouvier M, Tennant DA, Hudson BD, Gerhart-Hines Z, Milligan G, Schwartz TW, Calebiro D (2025). Intracrine FFA4 signaling controls lipolysis at lipid droplets. Nature Chemical Biology

The Translational Brain Science Research Group, led by Professor Alex Sinclair, investigates a range of impacts on the function and physical health of the brain, with a programme of research which aims to deliver improvements in the care of patients. Working with collaborators locally, nationally, and internationally on innovative studies, they seek to understand causes of illness, and develop new treatments, assess mechanisms, and translate knowledge into clinical services to improve the lives of those with brain injury or disease.

Her team investigates the role of metabolic disruption in neurological disorders such as migraine and idiopathic intracranial hypertension, using both clinical and experimental approaches. Professor Sinclair also collaborates with NASA to study how space flight and altered gravity affect the brain and intracranial pressure, providing unique insights into neurological health in extreme environments. She is also part of the Women’s Metabolic Health theme within the NIHR Birmingham Biomedical Research Centre, contributing her expertise to research that addresses the metabolic challenges faced by women across the lifespan.

Selected publications 

• Grech O, Rubio-Beltran E, Stanyer EC, et al. (2025). Raised intracranial pressure alters cortical vascular function and cephalic allodynia. Brain, 148(6):2163–2177
• Mitchell JL, Lyons HS, Walker JK, et al. (2025). A randomized sequential cross-over trial evaluating five purportedly ICP-lowering drugs in idiopathic intracranial hypertension. Headache: The Journal of Head and Face Pain