Dr Frederique Ponchel

Profile

Head of group since 2010: Translational Research in Immune Mediated Inflammatory Diseases

LIRMM, The University of Leeds, UK.

Sep-2016          Associate Professor, tenured

Apr-2010          Senior Lecturer, tenured

2005/10            University Academic Research Fellow

2000/05            Career Development Research Fellow (Arthritis Research UK)

1998/99            Senior Postdoctoral position

The p53 lab, Yorkshire Cancer Research, The University of York, UK 

1998/99            Senior Postdoctoral position 

1995/97            Postdoctoral Fellow (EU)

Laboratory of Molecular Oncology, INSERM 453, Lyon, France

1994/95             Postdoctoral Position (funded by  Ligue contre le cancer)

Harvard Medical School, MA, USA  &  Centre anti-cancer Leon Berard, Lyon, France

        1990/94             PhD student, joint program, 15 months in Boston, 2 years in Lyon (funded by IFSBM)

Since 1998, I have supported my research activities through a successful portfolio of research grants (£7M/€36M including consortia with a personal income (as PI) of >£4.6M), ranging from personal awards and projects, to program grant, clinical research fellowships, equipment and partnership in national  and international research networks (UK/EU/IMI) notably with industry.

Responsibilities

• PGRT lead for LIRMM
• E&I lead for LIRMM

Research interests

Since taking up my position at the University of Leeds in January 1998, I have worked towards creating a programme of work exploring the early events driving Rheumatoid Arthritis (RA). I lead a group (with currently 7 members), called: Translational Research in Immune Mediated Inflammatory Disease (TRIMID). TRIMID is seamlessly integrated within the Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM) and located at St James Hospital in a University Research building (WTBB).

Our research focus is centred on the molecular and cellular events that trigger the development of immune mediated inflammatory disease (IMID), taking rheumatoid arthritis as our main model but also looking at other musculoskeletal inflammatory diseases (osteoarthritis, ankylosing spondylitis and psoriatic arthritis).

As a group, we are aiming for international quality publications in the area of early mechanisms of disease development, biomarkers (including cellular, molecular and epigenetic candidates), prediction of response to therapy, management of remission and relapse, novel anti-IL-7 therapy, with an interest in mesenchymal stem cell repair capability. We have transferred some of our cellular biomarker work using flow cytometry to the NHS-routine services and are currently developing clinical trials based on stratification using these biomarkers.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joint that serve as a disease model for several Immune Mediated Inflammatory Diseases (IMIDs). A number of features suggest autoimmune mechanisms in RA (notably its genetic association with T-cells biology). Specific abnormalities within the T-cell compartment have suggested a possible defect in the generation and/or the maintenance of T-cells in RA (Ponchel et al. 2002). During the past 20 years, we have focused on identifying primary defects in T-cell development and maturation (T-cell differentiation) (Ponchel et al. 2002; Ponchel et al. 2005) anergy or activation (Ali et al. 2001), regulatory T cells (Ng et al, 2001; Lawson et al. 2006) and explored the role of IL-7 in RA (Ponchel et al. 2005; Churchman et al. 2007; Ponchel et al. 2011; Goëb et al. 2013; Ponchel et al. 2014). One of our current objectives is to exploit the knowledge’s accumulated in those areas; towards developing biomarker of diagnostic from the pre-clinical phases of RA and for the prediction of response to therapy as well develop novel means of blocking cytokines (using an artificial protein scaffold), using IL-7 as a prototype.

LIRMM is involved in a major effort to classify inflammatory arthritis states from early symptoms in order to facilitate diagnostic and enable earlier access to treatment. We have shown that the quantification of immunological biomarker such as naïve and regulatory T-cells using flow cytometry can discriminate early inflammatory arthritis patients who progress to RA (Ponchel et al. Submitted) as well as patients with better response to 1st line drugs (Ponchel et al 2014). We extended this work to demonstrate that such T-cell biomarker can be used to predict the onset of arthritis in “At Risk” individual (Hunt et al. 2015). We have transferred all protocols for this research to the NHS Immunology routine facilities. We expanded this work outside of Leeds as well as develop the capacity to receive and analyse samples from other centres (postal or by carriers).

We also investigate soluble markers (Goëb et al. 2013; Strollo et al. 2013; Churchman et al. 2012; Burska et al. 2014; Burska et al. 2014), gene expression signatures (Churchman et al. 2012; Burska et al. 2014) and epigenetic biomarkers.

As part of the TRIMID biomarker research program, we also demonstrated defects in immune homeostasis associated with ageing and osteoarthritis (OA) (Ponchel et al, 2015). We also established some important features of bone marrow oedema in OA (Campbell et al 2015). This work will be pursued with the development of new research projects notably investigating T and B-cell abnormalities and their possible role in pathology.

Another important breakthrough for the group was the association of IL-7 with RA pathogenesis (Ponchel et al. 2005; Churchman 2008) and its implication is several physiological processes (Ponchel 2014). These findings were completed with the validation of IL-7 as a candidate diagnostic biomarker for RA (Goëb et al. 2013; Burska et al. 2016). The development of anti-rheumatic therapies using IL-7 as a target has been proposed (Churchman 2008) and we are exploring IL-7 blockade in RA using 2 approaches (a small molecule and an engineered protein scaffold). We also developed an interest in Mesenchymal Stromal cells, as they are the source of IL-7 secretion in several tissues including joints (Jones et al. 2010; Goëb et al. 2012).

Group Members

• Dr Frederique Ponchel – Associate Professor; Head of Translational Research in Immune Mediated Inflammatory Diseases
  • Mrs Rekha Parmar – Senior Research Technician
  • Daniel Perez-Witzke - PhD Student
  • Rujiraporn Pitaksalee - PhD Student
  • Xie Xuanxiao - PhD Student
  • Katarina Mydlova PhD Student
  • Hanna Gul - PhD Student
  • Payal Ganguli - PhD Student (co-supervised)
  • Georgi Georgiev - PhD Student (co-supervised)

List of Projects

• T-cell biomarkers of progression in the inflammatory arthritis Disease continuum
• T-cell subset transfer of technology to NHS (collaboration with NHS)
• T-cell Polarisation: Th17 as biomarker (industrial collaboration)
• T-cell epigenetic to decipher early RA pathogenic event
• T-cell epigenetic biomarker discovery
• Tissue Architecture and IL-7 in RA
• IL-7 signalling blockade (collaboration with Biology)
• Immune signature in osteoarthritis  
• Bioethics and bio-banking 
• Biomarker of fracture non-Union  (collaboration with orthopaedics)

Qualifications

• PhD, 1994 Lyon France and Boston, USA
• DU, 1993 Paris France
• Master By Research, 1989 Paris, France
• Master, 1988, Paris France
• BSc, 1987, Paris France

Professional memberships

• BSR
• BSI

Student education

Lecture to MEDM5121M

BSc Molecular Medicine programe leader (2015-2017), closed.

Research groups and institutes

• Leeds Institute of Rheumatic and Musculoskeletal Medicine
• Immunity and inflammation
• Musculoskeletal disease

Current postgraduate researchers

• Daniel Perez-Witzke
• Xuanxiao Xie