University Associate Professor in Reproductive Biology
Department of Obstetrics and Gynaecology
Telephone +44 (0)1223 336873
Current Research Interests
- Imprinting, placental function and fetal growth
- Epigenetic basis of metabolic disease
For further information see Wellcome-MRC Institute of Metabolic Science
- MRC Investigator
- Principal Investigator of Wellcome-MRC Institute of Metabolic Science, University of Cambridge, UK (since 2007)
- Principal Investigator of the Centre for Trophoblast Research, University of Cambridge, UK (since 2008)
- Affiliated Professor Faculty of Medicine, University of Porto, Portugal (since 2012)
- NET member of Epigenetics EU Network of Excellence (since June 2006)
- BBSRC David Phillips Fellow and Group Leader (2004-2007), The Babraham Institute, Cambridge, UK
- Career Progression Fellow (2003-2004), The Babraham Institute, Cambridge, UK
- PhD (2000), University of Cambridge, UK
- MSc in Cancer Biology (1993), University of Porto, Portugal
- BSc in Biology (1988), University of Porto, Portugal
Key Publications (selected throughout career)
Sandovici I, Georgopoulou A, Perez-Garcia V, Hufnagel A, Lopez-Tello J, Lam BYH, Schiefer SN, Gaudreau C, Santos F, Hoelle K, Yeo GSH, Burling K, Reiterer M, Fowden AL, Burton GJ, Branco CM, Sferruzzi-Perri AN, Constância M (2022) The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth. Dev Cell doi: 10.1016/j.devcel.2021.12.005. Online ahead of print. PMID: 34963058
Angiolini E, Sandovici I, Coan PM, Burton GJ, Sibley CP, Fowden AL, Constância M (2021) Deletion of the imprinted Phlda2 gene increases placental passive permeability in the mouse. Genes 12:639 doi: 10.3390/genes12050639. PMID: 33922969
Sandovici I, Hammerle CM, Virtue S, Vivas-Garcia Y, Izquierdo-Lahuerta A, Ozanne SE, Vidal-Puig A, Medina-Gomez G, Constância M (2021) Autocrine IGF2 programmes beta-cell plasticity under conditions of increased metabolic demand. Sci Rep 11:7717 doi: 10.1038/s41598-021-87292-x. PMID: 33833312
Hammerle CM, Sandovici I, Brierley GV, Smith NM, Zimmer WE, Zvetkova I, Prosser HM, Sekita Y, Lam BYH, Ma M, Cooper WN, Vidal-Puig A, Ozanne SE, Medina-Gomez G, Constância M (2020) Mesenchyme-derived IGF2 is a major paracrine regulator of pancreatic growth and function. PLoS Genet 16(10):e1009069. doi: 10.1371/journal.pgen.1009069. PMID: 33057429
Sferruzzi-Perri AN, Lopez-Tello J, Fowden AL & Constância M (2016). Maternal and fetal genomes interplay through phosphoinositol 3-kinase (PI3K)-p110alpha signalling to modify placental resource allocation. Proc Natl. Acad Sci USA, 113:11255-11260. PMID: 27621448. PMCID:PMC5056071.
Sandovici I, Hammerle CM, Cooper WN, Smith NH, Tarry-Adkins JL, Dunmore BJ, Bauer J, Andrews SR, Yeo GS, Ozanne SE & Constância M (2016). Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets. Diabetologia, 59:502-11. PMID:26699651. PMCID:PMC4742511.
Mikaelsson MA, Constancia M, Dent CL, Wilkinson LS and Humby T (2013). Placental programming of anxiety in adulthood revealed by Igf2-null models. Nat Commun. 4:2311
Sandovici I, Hammerle CM, Ozanne SE, and Constancia M (2013). Developmental and environmental epigenetic programming of the endocrine pancreas: consequences for type 2 diabetes. Cell Mol Life Sci. 70:1575-1595
Sandovici I, Hoelle K, Angiolini E and Constancia M (2012). Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming. Reprod Biomed Online. 25: 68-69
Haley VL, Barnes DJ, Sandovici I, Constancia M, Graham CF, Pezzella F, Buhnemann C, Carter EJ, and Hassan AB (2012). Igf2 pathway dependency of the Trp53 development and tumor phenotypes. EMBO Mol Med. 4: 705-718
Khulan B, Cooper WN, Skinner B, Bauer J, Owens S, Prentice AM, Belteki G, Constancia M, Dunger D, and Affara NA (2012). Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. Hum Mol Genet. 221: 2086-2101
Cooper WN, Khulan B, Owens S, Elks CE, Seidel V, Prentice AM, Belteki G, Ong KK, Affara NA, Constancia M, and Dunger DB (2012). DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. FASEB J. 26: 1782-1790
Ozanne S, Sandovici I, and Constancia M (2011). Maternal diet, aging and diabetes meet at a chromatin loop. Aging 3:548-554
Sandovici I, Smith NH, Dekker-Nitert M, Ackers-Johnson M, Uribe-Lewis S, Ito Y, Jones RH, Marquez VE, Cairns WJ, Tadayyon M, O’Neill LP, Murrell A, Ling C, Constancia M, and Ozanne S (2011). Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at Hnf4a gene in rat pancreatic islets. Proc. Natl. Acad. Sci. USA. 108: 5449-5454
Sferruzzi-Perri AN, Vaughan OR, Coan PM, Suciu MC, Darbyshire R, Constancia M, Burton GJ, and Fowden AL (2011). Placental-specific Igf2 deficiency alters developmental adaptations to undernutrition in mice. Endocrinology. 152: 3201-3212
Angiolini E, Coan P, Sandovici I, Iwajomo OH, Peck G, Burton GJ, Sibley CP, Reik W, Fowden AL, and Constancia M (2011). Developmental adaptations to increased fetal nutrient demand in mouse genetic models of Igf2-mediated overgrowth. FASEB J. 25: 1737-1745
Petry CJ, Evans ML, Wingate DL, Ong KK, Reik W, Constancia M, and Dunger DB (2010). Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19 delta 13. Diabetes. 59: 282-286
Dilworth M, Kusinski L, Cowley E, Ward S, Husain S, Constancia M, Sibley C, and Glazier J (2010). Placental-specific Igf2 knockout mice exhibit hypocalcemia and adaptive changes in placental calcium transport. Proc Natl. Acad. Sci USA. 107: 3894-3899
Ozanne S and Constância M (2007). Mechanisms of Disease: The developmental origins of disease and the role of the epigenotype. Nat Clin Pract Endo & Met. 3: 539-546.
Constância M, Angiolini E, Sandovici I, Smith P, Smith R, Kelsey G, Dean W, Ferguson-Smith A, Sibley CP, Reik W and Fowden A (2005). Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems. Proc Natl Acad Sci USA. 102: 19219-24.
Sibley CP, Coan PM, Ferguson-Smith AC, Dean W, Hughes J, Smith P, Reik W, Burton GJ, Fowden AL and Constância M (2004). Placental-specific Insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta. Proc Natl Acad Sci USA (2004) 101:8202-8.
Constância M, Kelsey G and Reik W (2004). Resourceful Imprinting. Nature 432: 53-7.
Constância M, Hemberger M, Hughes J, Dean W, Ferguson-Smith A, Fundele R, Stewart F, Kelsey G, Fowden A, Sibley C and Reik W (2002) Placental Igf2 is a major modulator of fetal growth. Nature 417: 945-948.
Constância M, Dean W, Lopes S, Moore T, Kelsey G and Reik W (2000). Deletion of a silencer element in Igf2 results in loss of imprinting independent of H19. Nature Genet 26: 203-206.