Institute of Cellular Medicine

Staff Profile

Dr Kevin Marchbank

Senior Lecturer in Complement Therapeutics

Background

Introduction

I am complement biologist and B cell immunologist with a focus on kidney and eye disease.

My research group is part of the newly formed Complement Therapeutics Research Group which includes the groups of Prof Claire Harris, Prof Neil Sheerin and Dr David Kavanagh.

please see our renal research in Newcastle

We are a key component of the National Renal Complement Therapeutics Centre (NRCTC), RVI, Newcastle-upon-Tyne. Click here to see the NRCTC web pages


My current interests are the role of anti-complement protein autoantibodies in aHUS and C3G (MPGN). The development of Factor H based therapeutics, primarily for the treatment of C3G and aHUS. This sits along side a long standing interest in the role of CR2 in B cell function and the use of complement proteins as adjuvants in vaccine design.

Background

1989-1993 Obtained an upper class 2 degree (2\1) in B.Sc. (Hons) Immunology from the University of Glasgow

1993- 97 Obtained Ph.D., based on “Cell resistance and recovery after complement attack: The role of CD59” under the supervision of Professor B. Paul Morgan & Dr Carmen W. van den Berg.

1997-2000 Awarded a prestigious Wellcome Trust prize international fellowship to generate human complement receptor 2 transgenic mice within Prof. V. Michael Holers laboratories in the Dept. of Medicine and Immunology, UCHSC, Denver, CO, USA.

2000-0ct 2002 In continuation of the Wellcome Trust Prize International Fellowship, I returned to Prof. B. Paul Morgan’s laboratories in Cardiff, Wales to fully develop my research on the hCR2 transgenic mice.

Oct 2002- Oct 2006  Obtained a Wellcome Trust research career development fellowship (RCDF), at the UWCM (now Cardiff University) where I established a small research group examining the links between the innate and the humoral immune systems and began to develop 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-Dec 2008. Accepted a position as Lecturer in Medicine (nephrology) within the Institute of Human Genetics, Newcastle University where I developed an interest in the role of the immune system in atypical haemolytic ureamic syndrome and membranoproliferative glomerulonephritis.

Jan 2009 - present. Transferred within Newcastle University to the newly formed Institute of Cellular Medicine and the Applied Immunobiology grouping. I am now part of Inflammation, Immunology and Immunotherapy. Please see research for current ongoing projects.

Roles and Responsibilities

Group leader, research focus on the complement system, kidney and eye disease, vaccine adjuvants based on C3d, and the development of FH based therapeutics, see research.

Provide lectures and laboratory projects to all levels students at Newcastle University 

Nov 2015 to present:- Head of Excellence in Learning and Teaching; ICM. 

Co-Lead of ICM Equality and Fairness committee

Head of autoimmune aHUS research and analysis (NRCTC).

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

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

Renal Association

aHUS Rare disease group of RADAR

MPGN/DDD/C3G Rare disease group of RADAR

Honours and Award

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

Research Interests

The complement system (Innate immunity), particularly Factor H, Factor H related proteins and C3 in both mouse and man.
Autoantibodies (in Kidney Diseases)
B cell development and the Humoral Immune response.C3d as a molecular adjuvant.

Other Expertise

Transgenic mice and certain Immune response models, Autoantibody ELISA (specifically anti Factor H ). Complement factor H related proteins. C3 Glomerulopathy (C3G) or Membranoproliferative glomerulonephritis (MPGN) and atypical Haemolytic ureamic syndrome (aHUS).

Current Work

>AutoAbs to Factor H . We have published several articles on the involvement of anti-Factor H autoantibodies in the development of aHUS and C3G.

>Understanding the function of complement factor H related proteins (FHRs) through the development of unique monoclonal antibodies and recombinant protein assays. We are working with Prof Mike Holers team in Denver Colorado to study the mouse FHRs and have recently investigated CFHL1 through funding from the NCKRF.

>Proof of concept funding looking at novel bacterial protein based adjuvants. 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 are currently working on use of proteins designed to capture this function to aid vaccine delivery and potency we are also working with colleagues in Bath to improve vaccine transport. See our recent work in this area.

> anti-complement Therapeutics: Development of targeted factor H (FH) fusion proteins in order to protect the kidney from run away C activation. We are using existing (CR2-FH and Mini-FH) and novel strategies (homo-dimeric mini-FH) to target the C inhibitory domains of FH to the kidney (and the eye).

> C3 gain of function study: We have developed a unique C3 gain of function comparative model to investigate the mechanisms that pre-dispose to aHUS, the mechanisms that lead to pathology in the disease and to investigate treatment solutions, such as homo-dimeric mini-FH.

Pet project; examining the role of C3 and CR2 in the development of B cell tolerance

Future Research

The role of complement in the development of AMD (development of novel models/treatments)

The development of new models of aHUS investigating the trigger and role of the coagulation pathway. 

 

Research Roles

Lab based scientist, currently writing grants and papers. My Group currently consists of 3 technicians, 4 PhDs (primary and co supervised), 2 PDRAs and 1 Clinical fellow

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

MRC CiC and BBSRC Funding to develop a vaccine adjuvant for mTB.

NCKRF and Newcastle Healthcare Charities supporting work surrounding the C3 gain of function model

Kidney Research UK supporting the investigation of mini-FH in C3G; PhD trigger events in aHUS and Project grant looking at use of anti-complement drugs in complement mediated renal diseases

Patents Filed.

P031134GB "Modified Complement proteins and uses thereof"

P030973GB "Recombinant mature Complement Factor I"

1619965.5 "Immunogenic compositions comprising Sbi protein and use thereof" (with University of Bath)

Teaching

Postgraduate Teaching

MRes research project supervision

MRes Lecturer, Complement in Health and Disease

 

Undergraduate Teaching (B940/B900)

CMB3000 Undergraduate research project supervision

BMS3021 Lecture on complement in health and disease, provide seminar

BGM3039 Lecture on complement therapeutics

MIC3044 Provide seminar



 

Publications