Professor of Lipidology
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, utilise the COPII vesicular transport system to navigate their journey through the complex intracellular transport system of enterocytes. Carol Shoulders joined the William Harvey Research Institute in 2009 to continue studies into the highly atherogenic, disorder Familial Combined Hyperlipidemia (FCHL) and to diversify into other areas of lipid biology, work begun at the MRC Clinical Sciences Centre, Imperial College London. Carol Shoulders is a committee member of the Heart-UK Research Board, a scientific advisor for the American Society of Biochemistry and Molecular Biology Today Journal and an Associate Editor for the Journal of Lipid Research.
Summary of Research
The group’s current research is focused on identifying the diverse range of cellular processes that contribute to whole-body lipid homeostasis Our approach involves identifying the causes of the pernicious, highly atherogenic disorder, Familial Combined Hyperlipidemia (FCHL); and characterizing 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 genetic linkage analyses, high-through-put sequencing, statistical analyses, bioinformatics, genome-wide gene expression analyses, cell and structural biology plus biochemistry.
Elucidating the Genetics and the Underlying Biology of FCHL-lipid Abnormalities.
From our FCHL studies (see cartoon), it is apparent that the genetic complexity of FCHL is rooted in the diversity of the intra- and inter-cellular processes of the various organs (e.g. liver, adipose tissue (see Chan), adrenal gland (see Metherell) that handle diverse ranges of lipid species. Crucially, our findings have already opened the door for developing more personalised, efficacious, therapies for this common and highly atherogenic disorder, and promise to provide new mechanistic insights into both its pathogenesis, and that of some seemingly unrelated genetic disorders.
Lipoprotein Production, ER-cholesterol Synthesis and ER-transport Vesicle Assembly.
We are investigating the post-transcriptional mechanisms regulating ER-cholesterol synthesis (see cartoon), the rationale being that most nucleated cells synthesis cholesterol de novo (e.g. adrenal for steroid synthesis, Metherell and King); and >50% of circulating cholesterol derives from de novo synthesis. We envisage that further delineation of the apoB-lipoprotein/cholesterol/COPII machineries will provide important insights into the nature and causes of ER-stress in metabolic, cardiovascular and endocrine disease.
Members of the Group
Research staff: Dr C Hutchison
Wellcome Trust Clinical Training Fellow: Dr R Sivapackianathan
PhD Student: Ms Tozen Ozkan
Click here to download PFIDO.
For a full list of publist publications click here
Aikio M, Elamaa H, Vicente D, Izzi V, Kaur I, Seppinen L, Speedy HE, Kaminska D, Kuusisto S, Sormunen R, Heljasvaara R, Jones EL, Muilu M, Jauhiainen M, Pihlajamäki J, Savolainen MJ, Shoulders CC, Pihlajaniemi T. (2014). Specific collagen XVIII isoforms promote adipose tissue accrual via mechanisms determining adipocyte number and affect fat deposition. Proc Natl Acad Sci 111(30):E3043-52. 10.1073/pnas.1405879111