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Institute of Metabolic Science

Metabolic Research Laboratories
 

Research focus

The overall focus of my research is to understand tissue-specific actions of imprinted genes (such as Igf2 - insulin-like growth factor type 2 and miR-483) during development. I also study the impact of sub-optimal environment during critical periods of development on epigenetic regulation of gene expression (particularly on altering promoter-enhancer interactions), with consequences for higher risk of metabolic diseases such as type 2 diabetes and obesity in later life. 

Background and experience

I grew up in Romania and studied medicine, initially training to be an oncologist. However, genetic influences upon human disease have always fascinated me. After my medical training, I did my PhD and I worked in several labs (USA and UK) before joining the IMS-MRL in 2008. The best thing about working in the IMS-MRL is the opportunity to collaborate with so many great scientists and to benefit from the infrastructure of the organisation with its excellent core facilities.  

Working at the IMS-MRL

I have several ongoing projects: 

  • Using novel loss-of-function and gain-of-function mouse models, I’m addressing the role of the imprinted microRNA miR-483 as a regulator of growth and metabolism. 

  • Using promoter-capture HiC (a method that enables the study of chromatin looping) and additional genome-wide techniques, I am searching for novel regulators of adipogenesis. 

  • Using multiomics approaches (transcriptome, DNA methylome and lipidome analyses), I study the impact of physiological aging on pre-adipocytes and mature adipocytes in mice. 

  • With a similar multiomics approach (transcriptome, DNA methylome, chromatin, and lipidome analyses), I am trying to uncover molecular markers of visceral white adipocyte dysfunction in human obesity-associated dysglycaemia.  

  • In collaborative work with the Sferruzzi-Perri lab, I am addressing the role of placenta endocrine function in modulating maternal metabolism during pregnancy and beyond. 

  • In collaborative work with the Miska lab, I am trying to understand the role of epigenetic mechanisms in the intergenerational inheritance of glucocorticoid-induced metabolic dysfunctions. 

I’m particularly proficient at the following techniques: 

  • Mouse phenotyping techniques (intra-uterine growth, development of specific endocrine organs such as pancreas, basic metabolic phenotyping); 

  • Molecular biology assays: analyses of gene expression (qRT-PCR, RNA-seq), DNA methylation (Mass Array, RRBS-seq, BS-seq), chromatin (ChIP, PC-HiC, q3C), cloning; 

  • Histology (standard stains, immunohistochemistry) and microscopy (standard and confocal); 

  • Standard statistical analyses. 

Awards

- Director’s Collaborative Award, 2022. This supported work in partnership with Benjamin Jenkins and Brian Lam. We performed lipidomics analysis in adipocytes isolated from intra-abdominal fat of dysglycaemic and normoglycaemic obese patients (March 2022) 

- Cambridge Reproduction SRI Development Fund, 2021. This award supported my career development through attending the On-Demand CRISPR Course organized by CamBioScience  

- Short Oral Presentation Prize Winner, 2020, at Genomic Imprinting – from Biology to Disease (Virtual Conference)  

Publications

Key publications: 

Sandovici I, Fernandez-Twinn DS, Hufnagel A, Constância M, Ozanne SE. Sex differences in the intergenerational inheritance of metabolic traits. Nat Metab. 2022 May; 4(5):507-523. 

Sandovici I, Georgopoulou A, Pérez-García V, Hufnagel A, López-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. The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth. Dev Cell. 2022 Jan 10; 57(1):63-79.e8. 

Napso T, Zhao X, Lligoña MI, Sandovici I, Kay RG, George AL, Gribble FM, Reimann F, Meek CL, Hamilton RS, Sferruzzi-Perri AN. Placental secretome characterization identifies candidates for pregnancy complications. Commun Biol. 2021 Jun 8; 4(1):701. 

Sandovici I, Hammerle CM, Virtue S, Vivas-Garcia Y, Izquierdo-Lahuerta A, Ozanne SE, Vidal-Puig A, Medina-Gómez G, Constância M. Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand. Sci Rep. 2021 Apr 8; 11(1):7717. 

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-Gómez G, Constância M. Mesenchyme-derived IGF2 is a major paracrine regulator of pancreatic growth and function. PLoS Genet. 2020 Oct 15; 16(10):e1009069. 

Senior Research Associate
Constância group

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