Professor Carol Shoulders

Profile

Carol Shoulders graduated from the Open University in 1980 whilst working at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge and was awarded a DPhil by Oxford University in 1983 for cloning the human apolipoprotein A1 gene. Her subsequent activities within the lipid biology field include identifying that mutations of the microsomal triglyceride transfer protein gene cause the devastating condition, Abetalipoproteinemia; and that the Abetalipoproteinemia gene-product belongs to the gene family which encodes the egg yolk protein, vitellogenin, and apolipoprotein B, the obligatory protein component of the major lipid carrying particles in the circulation. She also led the group which discovered the cause of the rare disorder Chylomicron Retention Disorder, and established that newly assembled chylomicrons, despite their very large size, utilize the COPII vesicular transport system to navigate their journey through the complex intracellular transport system of enterocytes. For 13 years, she served as an Associate Editor for the Journal of Lipid Research.

Carol Shoulders joined the William Harvey Research Institute in 2009 to continue her genetic and mechanistic studies into the highly atherogenic, disorder Familial Combined Hyperlipidemia work begun at the MRC Clinical Sciences Centre, Imperial College London, and to diversify into other areas of lipid biology, including, for example, the cell-specific function and mechanisms of actions of the pseudokinase Tribbles 1, implicated in multiple pathologies. She is the Scientific Lead for the TRIBBLES Research and Innovation Network (TRAIN) coordinated by her close colleague Professor Endre Kiss-Toth at Sheffield University. The program brings together a group of leading European scientists working at the interface of the control of energy homeostasis, metabolism and innate immunity to characterise the how the interaction between these physiological systems influences the development of prostate cancer. She is also the Lead for the BSc Pharmacology and Innovative Therapeutics Module (BMD377) Classic Papers and Current Topics in Pharmacology, as well as a committee member of the Heart-UK Research Board.

Research

Group members

The group’s research is focused on identifying the diverse range of genetic factors and cellular processes that contribute to lipid homeostasis in a wide range of cells, including hepatocytes, adipocytes and macrophages. The rationale for being that most nucleated cells synthesis cholesterol de novo (e.g. adrenal for steroid synthesis) and >50% of circulating cholesterol derives from de novo synthesis. We envisage that further delineation of cell-specific processes regulating cholesterol and fatty acid homeostasis will provide important insights into the nature and causes of the cellular and physiological stress in immuno-metabolic, cardiovascular and endocrine diseases.

Our Specific Objectives include understanding the transcriptional regulation of genes encoding key immuno-metabolic proteins, such as Tribbles 1, and the working relationships between the ER-localized machineries that synthesize cholesterol and the COPII vesicles, which transport multiple proteins and lipid complexes to the Golgi apparatus, en route to their final destinations. Our principal experimental approaches include high-through-put sequencing, model cell systems, biological computational analyses, ChIP and confocal imaging. 

Key Publications

Collaborators

External

Professor Endre Kiss-Toth; Drs Ian Sudbery & Heather Wilson (University of Sheffield); Professor Boris Lenhard (Department of Molecular Sciences, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London; Computational Regulatory Genomics, MRC London Institute of Medical Sciences) 

Internal

Professors LA Metherell (WHRI); Prof KJ Linton (Blizard Institute)