Professor John Loughlin
Prof of Musculoskeletal Research

Introduction

I did my PhD in developmental biology at Leeds University and subsequently carried out postdoctoral studies with Professor Bryan Sykes at the Institute of Molecular Medicine at Oxford University. These entailed a molecular genetic analysis of monogenic and polygenic diseases of the musculoskeletal system. I subsequently obtained a fellowship from the Arthritis Research Campaign and established a group at the Wellcome Trust Centre for Human Genetics. At that point my focus became the genetic analysis of osteoarthritis (OA) and in 2008 I moved to Newcastle as Professor of Musculoskeletal Research.

Roles and Responsibilities

  • Head of the Osteoarthritis Genetics Group, Institute of Cellular Medicine (ICM)
  • Member of the ICM's management board
  • Mentor for early-stage independent investigators, ICM

Qualifications

  • 1999 MA University of Oxford
  • 1991 PhD Molecular and Developmental Biology, University of Leeds
  • 1987 BSc (Hon) Biochemistry, Liverpool John Moores University

Previous Positions

  • 2002-2007 Lecturer in Musculoskeletal Sciences, University of Oxford
  • 1997-2002 Arthritis Research Campaign Fellow, University of Oxford
  • 1995-1997 Postdoctoral Scientist, Wellcome Trust Centre for Human Genetics, University of Oxford
  • 1991-1995 Postdoctoral Scientist, Institute of Molecular Medicine, University of Oxford

Memberships

I am a member of the following professional societies:

Research Interests

My groups principal research focus is identifying and then characterising those genes that confer risk towards the development and progression of osteoarthritis (OA).

Through a combination of linkage and association analysis the group has identified several genes harbouring susceptibility alleles for OA, including the genes GDF5, BMP5, DIO2, COG5 and COL11A1.

Our efforts are directed towards comprehensive functional analysis of the associated variants within these genes, and in others that are emerging from ongoing scans.

Current Group Members:

  • Dr Louise Reynard - research fellow
  • Mr Andrew Dodd - PhD student
  • Ms Madhu Ratnayake - PhD student
  • Ms Catherine Syddall - PhD student
  • Ms Emma Raine - PhD student
  • Mr Yaobo Xu - PhD student

Current Work

I was the principal investigator and coordinator of arcOGEN, a UK consortium of 16 investigators from 9 UK universities, whose aim was to conduct a powerful genome-wide association scan on 8000 OA cases and 11000 controls (www.arcogen.org.uk/). This study was supported by Arthritis Research UK (www.arthritisresearchuk.org/) with a grant of £2.2 million.

The scan is complete and the data analysed. We identified 5 highly significant signals, which cross the threshold for genome-wide significance, and 3 signals that are very close to being genome-wide significant. Our findings have been submitted for publication and the arcOGEN resources will soon be made available to other investigators.

I also have an active interest in those monogenic diseases of the extracellular matrix that have secondary OA as a phenotypic component, partly because these can highlight potential candidate genes for our primary OA studies.

I have also established collaborations with clinicians and scientists investigating other common complex phenotypes, including developmental dysplasia of the hip and exceptional longevity.

Many of the loci that my group investigate harbour polymorphisms that influence gene expression and this has stimulated a new research area in my group, an analysis of the tissue-specific effects of cis polymorphism on allelic expression imbalance.

The technical expertise that my group employs includes:

  • linkage analysis of monogenic and polygenic diseases
  • association analysis by case-control and family-based methods
  • gene expression analysis, in particular investigating differences at an allelic level
  • in vitro studies of gene expression using luciferase reporter assays and EMSAs
  • analysis of cell-signalling pathways by protein expression studies and western analysis
  • identification and characterisation of trans-acting factors using ChIP
  • characterisation of cis and trans factors by RNA knockdown 
  • epigenetic analysis of CpG sites in candidate loci using cell lines and tissue from human donors
  • the analysis of the cartilage transcriptome by RNA-sequencing
  • the identification of novel mutations in Mendelian pedigrees by exome sequencing
  • the identification of rare polymorphisms in OA susceptibility loci by next generation sequencing

Future Research

My groups main effort for the next 5 years will be to complete the genetic mapping of OA susceptibility loci and to carry out detailed functional studies of the loci identified such that we can understand clearly how the associated variants influence OA disease risk. This information will then be applied to develop improved diagnostic and prognostic tools and to facilitate the development of new intervention strategies, including novel therapeutics.

Postgraduate Supervision

I have considerable experience of postgraduate supervision and I currently supervise five PhD students; one who has just started her second year, three who have just started their third year, and one who has just completed his laboratory studies and is now writing up. I encourage undergraduates who have a keen interest in genetics and the functional analysis of disease loci to get in touch.

Esteem Indicators

  • Secretary General of OARSI, the principal international OA research society (2010-2013)
  • Moderator for the pre-congress workshop on "Genetics, genomics and functional analysis of OA susceptibility", OARSI Congress, Barcelona, 2012
  • Chair of the second OA Biomarkers workshop, Atlanta, USA, 2010
  • Member of the Biomedical Sciences Panel of Arthritis Research UK (until 2013)
  • Member of the Board of Directors of OARSI (2007-2013)
  • Member of the Editorial Boards of the journals Osteoarthritis & Cartilage, BMC Musculoskeletal Disorders, Longevity & Lifespan
  • Expert reviewer for INSERM, France, and scientific advisor to NIAMS, NIH, USA
  • Program committee member and session chair, OARSI Congress
  • Member of the Faculty of 1000 Medicine
  • Presented my groups research, and overviews of the research area, at international conferences in Europe, North America and Asia (35 oral presentations in the past 5 years) 

Funding

Principal investigator on over 20 grants, co-applicant on an additional 8. Total grant income to date > £15 million.

Undergraduate Teaching

  • Lecturer in Molecular Genetics 
  • Supervisor for undergraduate laboratory projects
  • MBBS marker
  • Tutor for Biomedical Sciences 

 

Postgraduate Teaching

  • Lecturer for the MRes course in Musculoskeletal Biology
  • Lecturer for the MRes course on the Genetics of Common Diseases 
  • Supervisor for MRes laboratory projects