Dr Kevin Marchbank
Nephrology

  • Email: kevin.marchbank@ncl.ac.uk
  • Telephone: +44 (0) 191 222 5998
  • Fax: +44 (0) 191 222 8988
  • Address: Institute of Cellular Medicine
    3rd Floor William Leech Building
    The Medical School, Newcastle University
    Framlington Place
    Newcastle-upon-Tyne,
    NE2 4HH

Introduction

I am an B cell Immunologist and complement biologist.
My current interests focus on the role of anti-Complement protein autoantibodies on disease susceptibility in aHUS and MPGN. I also have a long standing interest in the role of CR2 in B cell development and function.

Background

1989-1993 The University of Glasgow

Obtained an upper class 2 degree (2\1) in B.Sc. (Hons) Immunology.
Main laboratory project I undertook as part of the course was based on optimisation of western blotting techniques for the detection of auto-Abs (supervised by Dr E. Holmes). Also carried out a summer project assaying for the presence of immunological activation products in gut lavages derived from patients with Crohn's disease and Ulcerative Colitis (supervised by Dr L. Mc Lintoch at the gastro-intestinal laboratories, Western General Hospital, Edinburgh).

1993- 97 University of Wales College of Medicine (UWCM).

Received a U.W.C.M. Ph.D. scholarship under the supervision of Professor B. Paul Morgan, Medical Biochemistry, UWCM, Cardiff, UK. Co-supervision in the lab was provided by Dr Carmen W. van den Berg.

Obtained Ph.D., Title of thesis is “Cell resistance and recovery after complement attack: The role of CD59”. The majority of the research presented in this thesis is published (see below).

1997-2000. University of Colorado Health Sciences Center (UCHSC).

Awarded a prestigious Wellcome Trust prize international fellowship to generate transgenic mice that would reconstitute the mCR1/CR2 knockout mouse with human complement receptor 2. This work was carried out and the primary aim met in Prof. V. Michael Holers laboratory in the Dept. of Medicine and Immunology, UCHSC, Denver, CO, USA.

2000-0ct 2002. UWCM

In continuation of the Wellcome Trust Prize International Fellowship that was awarded in 1997, I returned to Prof. B. Paul Morgan’s laboratory at the UWCM to further develop my research on the hCR2 transgenic mice. This research has been expanded to include studies looking at the newly generated CD59 knockout mouse as well as the many other complement inhibitor/receptor animals and models available through Prof. B. Paul Morgan’s laboratory.

Oct 2002- August 2004, Wellcome Trust research career development fellowship (RCDF), and August 2004- Oct 2006 Lecturer and Wellcome RCDF UWCM/ Cardiff University

I established a small research group examining the links between the innate and the humoral immune systems using the human Complement receptor type 2 transgenic mice I generated in Denver. I am also developing a strong interest in the role of novel molecular adjuvants such as C3d trimers or octamers in generating improved vaccination profiles and reagents.

Oct 2006 forward. Took up position as Lecturer in Renal medicine at Newcastle university.

Roles and Responsibilities

Run a small research group looking a various aspects of the Complement system in human disease. 6 main research projects are currently underway, see research.

Qualifications

Doctor of Philosophy (Medical Biochemistry), UWCM, March 1997.
Diploma in Bio-Medical methods, UWCM, July 1994.
Bachelor of Science (2/1 hons) in Immunology, University of Glasgow, July 1993.

Previous Positions

Oct 2006 forward, Lecturer in Renal Medicine, Newcastle University
2002-2006, Wellcome Trust RCD fellow & Lecturer, Cardiff University
2000-2002, Wellcome Trust Fellow, University of Wales College of Medicine
1999 –2000 NIH Research Fellow, University of Colorado Health sciences center
1997- 1999, Wellcome Trust Prize travelling Fellow, University of Colorado Health sciences center

Memberships

British Society for Immunology,
International Complement Society,

Honours and Awards

2002 Research Career Development Fellowship, The Wellcome Trust
1997 Prize International Travelling Fellowship, The Wellcome Trust
1993 PhD scholarship, University of Wales College of Medicine

Informal Interests

Keen hiker, photographer, amateur artist and enjoy stimulating conversation, meeting new faces and as such have always enjoyed travel.

Research Interests

The complement system (Innate immunity), particularly CD59, C3, CR2 and Factor H.
Autoantibodies in Kidney Disease
B cell development and the Humoral Immune response.

Other Expertise

Transgenic mice and certain Immune response models, Autoantibody ELISA (specifically anti Factor H in aHUS). Complement factor H related proteins. Membranoproliferative glomerulonephritis (MPGN) and atypical Haemolytic ureamic syndrome (aHUS).

Current Work

· Project grant funding: AutoAbs to Factor H and Factor I. We have recently published several articles on the involvement of anti-Factor H autoantibodies in the development of aHUS. We have recieved three key grants (MRC, KRUK, Kids kidney research)to further expand this work to investigate MPGN and also autoantibodies to other important C regulators

. MRC funded PhD project. Characterisation of the function of complement factor H related proteins through the development of unique monoclonal antibodies and recombinant protein assays. We are also interested in the specific serum levels of these proteins in diseases such as aHUS and MPGN.

· PhD project looking at novel C3d based adjuvants. aims: C3d, a breakdown fragment of the complement protein C3, through its binding to complement receptor 2 has been shown to amplify the humoral immune response to antigen many fold.
We have generated a novel DNA which should strongly bind and activate B cells. We are currently testing this fusion protein elicits a greater immune responses than native antigen and whether the route of administration matters. We are also testing its function on ex vivo B cells.

. KRUK PhD project: Development of targeted CFH fusion proteins in order to protect the kidney from run away C activation. We are using existing and novel strategies to target the C inhibitory domains of Factor H to the GBM with a hope to show improvement in both acute and chronic kidney disease scenarios.

. Pilot study; generation of mutant murine C3 molecules that should have increased C3 activation potential (super C3) with a view to developing an aHUS disease model to investigate treatment solutions.

. Pet project; examining the role of C3 and CR2 in the development of B cell tolerance as well as B10 B regulatory cells

Future Research

Development of Multiplex assay for detection of C autoantibodies.

Development of a new Zinc inducible mCR2 in vivo model aimed at understanding the role of the complement system in the balance between tolerance and autoimmunity; is CR2 key to the development of B regs and does the complement system play a role in ageing immune system.

Develop super C3 model

Research Roles

Lab based scientist, currently writing a lot of grants and papers. Currently Supervise one Technician and 3 PhDs

Postgraduate Supervision

Scott J Staniforth, Yonggang He, Iain Moore and Eva-Maria Hunze

Esteem Indicators

Invited Tutor at the 16th European Meeting for Complement in Human Disease conference in Hungary september 2009.
Invited member of recently established MPGN (DDD) Rare Kidney diseases sub-group of the Renal association.
Founder member of Complement UK
Part of the International Complement Societies standardisation team with respect to development of a standard anti-FH autoantibody ELISA

Funding

Oct 2007- Oct 2011, MRC 4 year Mres/PhD studentship 25K. July 2008-March 2012, MRC project grant £350K. Oct 2008 - 0ct 2010 JRES project funding 24K. Oct 2009 - sept 2012 KRUK PhD studentship. June 2010 - May 2011, £65K; NCKRF pilot study grant £8K; KRUK Project grant oct 2010 to sept 2012 £128; Kids Kidney research project grant Jan 2011 to dec 2011, £56.

Patents

None as yet

Postgraduate Teaching

T cells lecture in Immunobiology module.