Dr Rhian Thomas

Dr Rhian Thomas

Lecturer in Pharmacology

Email:
thomasrs2@cardiff.ac.uk

Qualifications

  • PhD Biosciences, Cardiff University

Research Interests

  • Alzheimer’s disease
  • Antibody based therapies
  • Underlying mechanisms of disease

Undergraduate

    • Module Leader (PH1124)
    • Molecule to Patient (PH1121)
    • Human Body Systems (PH1124)
    • Chemical and Biological Properties of Drug Molecules (PH1125)
    • Principles of Drug Design (PH2112)
    • Diseases and Drugs I (PH2113)
    • Diseases and Drugs II (PH3113)
    • Research Methodology (PH3202)
    • Pharmacy Research of Scholarship Project (PH4116)

Postgraduate - Cardiff Dental School

  • MSc Tissue Engineering

Current Research Students:

  • Charles Evans, PhD student “Development and Characterisation of an anti-amyloid precursor protein antibody as a potential therapy for Alzheimer’s disease”
  • Adam Brelsford, PhD student “The effect of amyloid pathology on affective and cognitive processes in mice”
  • Anna Burt, PhD student “Creating polygenic cell-based models of Alzheimer's Disease”

Research interests

  • Alzheimer's disease
  • Antibody based therapies
  • Underlying mechanisms of disease

My research has been directed at two main areas: cell signalling in disease and amyloid production in Alzheimer’s disease (AD).  

There are two characteristic neuropathological features of AD, neurofibriallary tangles made of hyperphosphorylated tau and extracellular senile plaques made primarily of amyloid-beta, a 40-43 amino acid peptide produced from amyloid precursor protein (APP). An increase in amyloid-beta levels (especially amyloid-beta 42) is thought to be crucial for the pathogenesis of AD. Amyloid-beta is produced from the protein APP by cleavage events involving the enzymes beta- and gama-secretase which cleave APP sequentially to liberate amyloid-beta. Since the discovery of beta-secretase, an aspartic protease called beta-site APP-cleaving enzyme (BACE1) in 1999, there has been much interest in developing inhibitors.

My primary focus has been on investigating how amyloid-beta is produced in Alzheimer’s disease, what affects this and developing therapies to influence this.  Our laboratory is interested in developing novel therapeutic antibodies for AD that inhibit amyloid-beta. The antibodies I developed were unusual in that, rather than raising antibodies to amyloid-beta or BACE, the antibodies were raised to APP itself, in the vicinity of the BACE cleavage site. We demonstrated these antibodies successfully reduced amyloid-beta secretion from human cell lines and are now elucidating their effects in vivo.

My current interests include the understanding of amyloid-beta generation, particularly in relation to the role of clathrin-dependent and -independent endocytosis. I am currently involved with investigating how caveolin proteins contribute to the generation of this peptide and affect APP metabolism. There is growing evidence to link the caveolin proteins involved in non-clathrin-dependent endocytosis to various aspects of AD, since some studies have reported higher levels in diseased brain tissue. The mechanisms behind this are, however, unclear and our laboratory has a project funded by BRACE (Bristol Research into Alzheimer’s and Care of the Elderly) which aims to clarify this situation. Our data suggests that caveolins may actually sequester APP away from amyloid producing enzymes and hence reduce amyloid levels. In a related piece of work, I have identified important changes in the levels of endocytic-related proteins in the brains of Tg2576 transgenic  models of AD. We have now extended these areas of investigation and been funded by BRACE to look at clinical samples of human brain tissue, comparing changes in endocytic proteins in normal ageing with AD.

Current and Recent Grants

  • Cardiff School of Pharmacy and Pharmaceutical Sciences and Cardiff School of Psychology PhD Studentship, October 2012 - September 2015: Development and Characterisation of an anti-amyloid precursor protein antibody in vivo as a potential therapy for Alzheimer’s disease. EJ Kidd, M Good, RS Thomas
  • Bristol Research into Alzheimer’s and Care of the Elderly (BRACE) Project grant, September 2014-February 2016, ‘The influence of altered endocytic protein expression on the predisposition to develop Alzheimer’s disease’. E.J. Kidd and R.S. Thomas
  • BBSRC Sparking Impact Award 01/11/2013:  Determination of the affinity of the potential therapeutic antibody for Alzheimer’s disease, 2B3, for amyloid precursor protein
  • Welsh Government, 01/11/2011: Cardiff Early Stage Development Fund - Development of a potential therapeutic antibody for Alzheimer’s disease
  • Bristol Research into Alzheimer’s and Care of the Elderly 01/03/2012: The involvement of lipid raft proteins in the processing of amyloid precursor protein