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Dr Mark Christian

 

Title   

Associate Professor
 

Contact   

WMS - Cell and Development Biology
University of Warwick
Coventry
CV4 7AL
Tel: 024 76 968585
Email: M.Christian@warwick.ac.uk

Research Interests

1) Lipid droplet induction due to CIDE proteins
The study of factors that control lipid storage in different tissues is essential for understanding and controlling metabolic disorders. Cellular lipid storage is determined by a group of proteins that coat lipid droplets and facilitate storage or utilisation by regulation of metabolic processes. In mammalian cells, these lipid-coating proteins are members of the PAT (perilipin-ADRP-TIP47) domain family, which include perilipin, ADRP (or adipophilin), TIP47, S3-12 and MLDP/OXPAT. Recently, additional proteins, including CIDEA by our own investigations, have been discovered to have important roles in lipid droplet formation and function. We found that CIDEA can induce lipid droplets in non-adipocyte cells and is localized on the surface of these organelles. We are investigating the regulation and in vivo roles of CIDEA and the related proteins CIDEB and FSP27 in lipid accumulation.

2) Characterising the temperature dependent switch from white to brown adipocytes
As part of the DIABAT consortium (www.diabat.org) we are defining the genes that promote brown fat induction, transdifferentiation and activation of the energy expenditure program will provide new applications for combating the obesity epidemic. We aim to (i) determine the factors and pathways that define the switch from WAT to BAT-like adipocytes following cold exposure and (ii) identify the genes and pathways that discriminate WAT and BAT depots. As visceral WAT is considered significantly more detrimental to metabolic health in comparison to subcutaneous WAT (iii) we are also characterizing the pathways and genes that discriminate these two white fat depots.

3) The role of fatty acid signalling in adipocyte biology
Dietary fat has been correlated with obesity since it induces the proliferation and differentiation of pre-adipocytes. However it has become clear that the effect of fat on human health depends on the composition and the nature of fatty acids. We are studying intracellular signalling and G protein-coupled receptor signalling mediated by fatty acids in adipocyte cell systems.

4) The importance of microRNAs in endometrial differentiation
MicroRNAs (miRNAs) are genomically encoded, small, non-coding RNAs that regulate gene expression by controlling translation or stability of mRNAs. There are greater than 400 miRNAs identified, many of which display tissue specific expression patterns. They are key components in the regulation of developmental events and are required for cell fate specification and differentiation. During the menstrual cycle, ovarian estradiol and progesterone stimulate the ordered growth and differentiation of endometrial tissue compartments. We are studying microRNAs and their target genes involved in decidualization of human endometrium, defining their roles in regulating decidual cell function and examining if aberrant microRNA expression is associated with reproductive failure.


Biography

My laboratory is focused on determining the mechanisms that regulate gene expression in development and metabolism. We are characterising cells of the anatomically distinct white and brown adipose tissue depots and defining the action of hormones and dietary stimuli on adipocyte biology.

WAT and BAT
Energy homeostasis is crucial since excess fat storage leads to obesity and negatively impacts the body's metabolic health with associated predisposition to diseases including diabetes. There are two distinct types of adipose tissue: 1) White adipose tissue (WAT), when in excess, is considered to negatively impact on health due to its role in triglyceride storage and associated obesity. 2) Brown adipose tissue (BAT), in contrast, is considered to be favourable to health. Exposure to the cold rapidly activates signalling pathway in BAT which modulate gene expression and promote the capacity for thermogenesis and consumption of fat stores. Remarkably, WAT depots can also respond to a long term cold stimulus by specific genetic and morphological changes that result in a more BAT-like appearance. These changes could arise due to specific development from stem cells or preadipocytes in the WAT depot or transdifferentiation of fully mature adipocytes.

CIDE and Lipid Droplets
Investigating the ability of nuclear receptors and their coregulators to affect metabolic gene expression led us to the study of the biological roles of the CIDE (Cell Death-Inducing DFF45-like Effector) family of genes in lipid droplet induction and the control of energy metabolism in metabolic cells. By studying the function and regulation of this family of proteins, we are determining the impact of CIDE proteins on lipid storage in different metabolic tissues, the importance of controlling the expression of metabolic regulatory systems in response to environmental stimuli, and the impact of tissue-specific gene expression on whole body metabolic function and in metabolic disease.

MicroRNAs and Decidualization
MicroRNAs are important regulators of gene expression and essential for cell differentiation. Determination of the mechanisms that control gene expression in cycling endometrium is key to our understanding of normal fertility and pathological conditions, such as infertility, recurrent pregnancy loss, and a spectrum of obstetrical disorders associated impaired deep placentation, such as fetal growth restriction and preeclampsia.

Aims

  • To identify the molecular mechanism of CIDEA-dependent lipid droplet induction and determine its action in vivo.
  • To determine factors that control the switch between white and brown adipose tissue.
  • To determine the role of fatty acid signalling in adipocyte biology.
  • To determine the roles of microRNAs in endometrial differentiation.

Research Projects

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Publications

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