Dr Richard Pease

Profile

1975-1979   BA in Biochemistry, University of Oxford, 

1981-1984   PhD in Biochemistry, MRC Division of Clinical Cell Biology

1984-1987   Recombinant DNA training Fellowship, MRC Molecular Medicine Research   Group, Clinical Research Centre, Harrow

1987-1995   MRC non-clinical scientific staff.   MRC Molecular Medicine Research Group.  Royal Postgraduate Medical School

1995-1999   British Heart Foundation Intermediate Research Fellow, Department of Biochemistry and Molecular Biology, University College London

2000-Aug 2001   Wellcome Trust project grant holder (Principal Applicant), Department of Biochemistry and Molecular Biology, University College London

Feb 2002-present   Research Support Officer and Principal Research Fellow. Leeds Institute of Cardiovascular Medicine, LIGHT Laboratories University of Leeds

Responsibilities

• Co-lead for ICU 'Introduction to Medical Sciences'
• Lead for the Paper Commentary Module, iBSc in Cardiovascular Medicine

Research interests

Factor XIII-A introduces covalent cross-links into fibrin chains within blood clots, and its role in promoting clot stability is well-established. Patients who lack circulating FXIII-A are prone to life-threatening bleeds unless they receive intravenous injections of FXIII-A. On account of its ability to stabilise clots, it has also been suggested that thrombi might lyse more readily if FXIII-A is inhibited, and consequently that FXIII-A represents a potential drug target in the treatment of thrombosis. However, besides blood stabilizing clots, FXIII-A may also strengthen and repair blood vessels and protect the myocardium. Therefore, it has also been suggested that FXIII-A supplementation may be sometimes be appropriate to promote tissue repair, for example following myocardial infarction. A surprising feature of FXIII-A is that despite the fact that being present at moderate concentrations in the bloodstream, it lacks an ER signal sequence therefore it must be secreted by an unconventional route. Unconventional secretion is also a feature of other members of the transglutaminase family, and in particular, transglutaminase 2, an enzyme that has been implicated in tissue repair, but which does not stabilise plasma clots.

Although the unconventional secretory pathway of transglutaminase 2 has been reasonably well defined, our studies in cells expressing both transglutaminase 2 and FXIII-A indicate that transglutaminase 2 is secreted under conditions where FXIII-A remains cytosolic, i.e. they do not appear to share a common pathway. Neither does FXIII-A appear to share a common secretory pathway with interleukin 1-β, another prototypic non-classically secreted protein. However, several distinct intracellular trafficking pathways have recently been described by other groups, and it appears that in model cell systems, intracellular FXIII-A may partially co-localise with certain other proteins that are destined for unconventional secretion.

Recent cell-specific deletion experiments in mice floxed in the FXIII-A gene have indicated to us that resident macrophages are the secretory cell-type. We are currently developing methods to isolate these cells to verify that FXIII-A is sequestered to the same the compartments that were identified in the model cell systems. We are also carrying out transplant experiments with candidate precursor cells, perhaps opening up the possibility of cell-mediated therapy for individuals deficient in plasma FXIII-A.

We have also assessed the roles of FXIII-A and transglutaminase 2 in various arterial injury models, including atherosclerosis, myocardial fibrosis and aortic aneurysm and have identified distinct roles for each.  Currently we are seeking to understand how both transglutaminase exert their effects.

Qualifications

• PhD

Student education

I co-lead a course that introduces basic concepts in medical science to first year undergraduates studying for the MBChB medical degree. This involves giving some lectures on basic molecular and cell biology, but also acting as a tutor for a number of work-sessions on a range of topics related to medical science. In addition to the expected responsibilities of assisting with time-tabling, assessment and the recruiting of tutors and lecturers on the course, I take a particular responsibility for producing a student work-book that contains some self-directed work and some work that students complete during supervised sessions. This has involved shaping material initially suggested by other lecturers and clinicians concerned with the course to make it straightforward to deliver and to check for accuracy.

I assisted with the initial planning and development of a module for intercalating medical students on a cardiovascular medicine programme.  This involves familiarising students with published commentary articles in the scientific/medical press, and asking them to choose a primary publication that they consider to be of particular interest and to write a commentary on it.

I also give a lecture on energy metabolism to first year cardiac physiology and audiology students.

Research groups and institutes

• Leeds Institute of Cardiovascular and Metabolic Medicine
• Discovery and Translational Science
• Cardiometabolic