Dr Marie-Anne Shaw

Profile

I have a BSc in Genetics and Zoology and a PhD in Human Biochemical Genetics, both from University College London. I held several postdoctoral positions prior to coming to Leeds, the last two being at the London School of Hygiene and Tropical Medicine and the Department of Medicine, University of Cambridge. I was appointed as a lecturer at the University of Leeds in 1995. Although based in the School of Biology until 2012, I then moved to the Leeds Institute of Medical Research (formerly LIBACS) at St James’s University Hospital.

My research interests centre on analysis of human genetic susceptibility to heterogeneous, complex and multifactorial traits/diseases. I have brought together large field and laboratory datasets for genetic analysis, mainly from Africa and South America. I have been interested in data analysis throughout my career. Projects include:

• Non-infectious disease: the pharmacogenetic disorder malignant hyperthermia. This work started with my appointment at Leeds, and has become my main focus since transfering to St James's. The Malignant Hyperthermia Unit at Leeds, led by my collaborator Professor Hopkins, is the UK testing centre and the largest unit for this disease worldwide. This type of work is being expanded to consider genetic control of responsiveness to drugs and the environment e.g. heat and dietary additives.
• Infectious diseases: including susceptibility to cutaneous leishmaniasis, helminth infections and malaria. This work was a development of work carried out prior to my time at Leeds. All projects involve immunogenetics. Banks of  approximately 3,500 paired DNA and serum samples in total have been collected. For infectious disease, the days of considering host genetics in isolation are over. It is now essential to consider host and pathogen diversity in tandem, together with multiple environmental factors. This necessitates strong collaborative networks of field, laboratory and analytical researchers. 

Research interests

I have two main areas of interest: the adverse drug reaction malignant hyperthermia and related conditions, and the genetics of susceptibility to infectious disease. Malignant hyperthermia (MH) and related conditions are disorders affecting calcium homeostasis in skeletal muscle. Work is carried out in collaboration with the group of Professor Phil Hopkins. MH is triggered by inhalational anaesthetics and is potentially fatal if left untreated. Although MH is treated as an autosomal dominant disease, with many families showing mutation in the gene coding for the skeletal muscle form of the ryanodine receptor (RYR1), there is good evidence for modifier loci. Our interests are in identification of modifier loci and understanding the broader impact of major mutations eg for muscle ageing. 

Recently, work on the human disorder MH has been complemented by studies using Caenorhabditis elegans, based in the laboratory of Professor Ian Hope (Faculty of Biological Sciences).

My group has a long history studying the genetics of susceptibility to infectious disease. This has concerned a number of different host-pathogen systems with samples collected from around the world relating to bacterial, protozoal and helminth species. Although in most instances work has concentrated on the human host, some smaller projects have involved study of domestic species. Phenotypes may be disease per se or measures of immune responsiveness. Of course it is not possible to study the genetics of the host in splendid isolation and in some instances, such as for Mycobacterium tuberculosis, we have included information on pathogen diversity. This is the ethos behind the journal 'Infection, Genetics and Evolution', for which I am a founding editor.

For both areas we are considering complex, heterogeneous and multifactorial disorders with both qualitative and quantitative phenotypes. Projects involve genetic epidemiology – looking at large multigenerational pedigrees, mixed models and heritability and conducting segregation analyses. Candidate gene approaches focus on loci involved in calcium homeostasis and immunity respectively. Linkage analyses have largely been superseded by association methods relying on linkage disequilibrium, and we are applying whole genome approaches to MH. I have successfully supervised many PhD students with projects in diverse areas of genetics.

Qualifications

• PhD Human Biochemical Genetics
• BSc Genetics and Zoology (1st class)

Student education

With over 20 years at the University of Leeds, I have held many roles in student education, as a programme and module leader, but latterly focussing on course development.

On transferring to the School of Medicine in 2012, I developed and for the first 5 years acted as Programme Leader for the MSc Molecular Medicine. This programme was started in order to utilise the research expertise of the St James’s University Hospital site. The MSc in Molecular Medicine at Leeds is a Masters-level programme designed to enhance understanding of how to apply molecular approaches to the study, diagnosis, prevention and treatment of a range of cancers, chronic, autoimmune and genetic diseases. Students critically research and analyze different strands of Molecular Medicine and develop specialised knowledge in key areas of interest. Stimulating class-based learning by world renowned researchers over five months is matched by opportunities to network and learn from leading health professionals in a seven month laboratory-based research project. The MSc Molecular Medicine offers a large number of projects in diverse areas of applied and basic medical research; from over 100 world-leading academic staff, including a large number of cancer, biological, medicine and genetics projects. I continue to run the research project module for this programme. We are developing a related programme of MSc Cancer Biology and Therapy.

I have recently completed a period as Director of Intercalated Studies. Medical students, both internal and external, have the ability to intercalate on >20 programmes from several faculties at Leeds. This is in line with my long standing interest in devoloping cross faculty teaching at Leeds. Since 2016-17 I have run a scheme whereby undergraduates from the Faculty of Biological Sciences (up to 40) can conduct research projects in the School of Medicine. I am currently the School of Medicine representative leading development of cross faculty programmes, particularly with the Faculty of Biological Sciences.

Research groups and institutes

• Leeds Institute of Medical Research at St James's

Projects

<li><a href="//phd.leeds.ac.uk/project/457-limr-genetics:-investigating-the-functional-effect-of-novel-genes-and-genetic-variants-in-malignant-hyperthermia-using-model-systems">LIMR Genetics: Investigating the functional effect of novel genes and genetic variants in malignant hyperthermia using model systems</a></li>