I have held senior management responsibilities within the University and Institute and also serve on external Scientific Committee. For example:
Chair Institute Athena SWAN Steering Group (May 2012-present)
Member of University Senate (2009-2012).
University appointed Governor for Royal Grammar School (2010-2013).
Member of Northern Counties Kidney Research Fund Scientific Committee (2011-present)
Member of Institute of Celular Medicine Executive Board (2012-2014)
Member of MRes exam committee. (2007-present)
Institute Post-graduate coordinator (2004-2011).
Chair Institute Postgraduate Committee (2008-2011).
Member of Graduate School Committee.(2004-2011)
Member of Institute Management Committee. (2008-2011)
1984 BSc Chemistry (1st Class Honours). Aligarh University, India.
1986 MSc Biochemistry (1st Class). Aligarh University, India.
1991 PhD Biochemistry. Central Drug Research Institute, Lucknow, India
1990-91 Commonwealth Post-doctoral Fellow in Molecular Biology at UMIST, Manchester, UK.
1992-95 Post-doctoral Fellow at Department of Biological Sciences, University of Newcastle upon Tyne. Project funded by Biotechnology and Biological Sciences Research Council.
1995 (Sept) Lecturer in Molecular Biology of Organ Transplantation, Department of Surgery, University of Newcastle Upon Tyne. (Funded by Northern Counties Kidney Research Fund).
1999(Sept) Lecturer B, Department of Surgery (HEFCE funded)
2002 Senior Lecturer
2007 Reader in Immunobiology
2011 Professor of Molecular Immunology
British Society of Immunology, British Transplantation Society
Editorial Board Member of The Open Transplantation Journal and Open Transplantation Reviews
1. I was awarded special recognition award by Roche Organ Transplantation research Fund for my contribution to research in Transplantation (cash award of 1000 Swiss Francs)-April 2011.
2. Member of Northern Counties Kidney Research Fund Scientific Sub-Committee.
3.Reviewer for Faculty Proposal Appraisal Team (FPAT)
4.Regularly review grants for MRC, BBSRC, Cancer Research UK, British Heart Foundation, Wellcome, Asthma UK Foundation and Singapore Biomedical Research Council.
5.Editorial Board Member for “
• The Open Transplantation Journal
• Open Transplantation Reviews.
• Translational Biomedicine
My main area of research is studying the immunobiological processes that result in tissue damage, which has applications in transplantation immunobiology and cancer immunotherapy. This work is focused largely on the regulatory interactions between T lymphocytes and endothelial and epithelial cells. Within this area, specific interests include the role of cc chemokines in inflammation, their interaction with cell surface glycosaminoglycans and signal transduction mechanisms mediated by them.
My work so far has helped in clearly defining the role of chemokines in inflammation with particular relevance to transplantation. It has also demonstrated that in addition to binding to their specific G-protein coupled receptors, chemokines also interact with cell surface glycosaminoglycans (GAGs) (J Biol Chem: 276, 1721, 2000 ) and we pioneered the research revealing that heparin-like GAGs could inhibit chemokine activity (Immunology, 1997, 92:512-518). My subsequent work has convincingly shown that this chemokine-GAG interaction is essential for in vivo activity of these cytokines (J Immunology, 2005, 175, 1257). In addition I have shown the changes in cell surface heparan sulphate patterns in response to inflammation which in turn regulates cytokine function. This suggests that formation of glycosaminoglycan-stabilised cytokine concentration gradient play an important role in modulating the biological activity of the cytokine.
My other major interest has been examining the role of chemokine-chemokine receptor interaction in breast cancer metastasis in collaboration with Professor TWJ Lennard. We have established an in vivo model of Breast cancer metastasis and have shown significantly reduced metastasis in animals treated either with heparin or non-glycosaminoglycan binding chemokines. This successful collaboration has resulted in two PhD’s and I hope to expand this work and seek support from Cancer Research UK or national funding bodies. In addition, a Phase I Trial of the CXCR4 Chemokine Inhibitor AMD 3465 focussed on breast cancer has been proposed for funding by CRUK in collaboration with Hillary Calvert (NICR).
Ongoing Research: Chemokine receptors provide a suitable target for therapeutic limitation of inappropriate inflammation during disease and a range of small molecule antagonists are currently being developed and validated commercially for this purpose. Clinical trials using a variety of chemokine receptor antagonists have been initiated but, so far, none has progressed beyond phase II. Importantly, the multiple redundancy of both chemokine and chemokine receptor families suggests that optimal therapy will involve complex simultaneous blockade of more than one receptor. Leukocytes typically express a range of Gi-coupled chemokine receptors as well as a wide range of chemotactic and non-chemotactic GPCR. As these receptors may be engaged simultaneously or sequentially by multiple mediators at inflammatory sites, the cellular response is likely to be cross regulated. Based on my recent results I propose that an appropriate (non-chemotactic) chemokine receptor agonist can be used to inhibit multiple chemokine receptors, thereby producing powerful and robust anti-inflammatory effects.
I have recently been awarded a Wellcome Trust grant (2007-2010) to explore the mechanism of action of non-GAG binding chemokines as a potential anti-therapeutic agent. Additional grant from Roche organ transplant research fund will allow me to examine the potential of this modified chemokine to inhibit allograft rejection. Due to my collaborative links with Aberdeen (Dr I Crane, for examining in vivo trafficking of leukocytes in experimental autoimmune uveitis) and Edinburgh Inflammation research centre (mouse skin transplant) I think that we are well positioned to carry out this current programme of work.
1.Assess the potential of mutant chemokines/heparinoids in animal disease model: I would like to move this work from bench to bedside. I have close links with academic surgical colleagues who lead the clinical heart, lung, kidney and liver transplant programmes in Newcastle. I am aware of defined funding streams which support the bench to bedside research and will be approaching them (e.g. MRC). We have an ongoing study in AITRG which is looking at rat lung transplants; I would be keen to examine the use of mutant chemokines or heparinoids in reperfusion with a view to ameliorate ischaemia reperfusion injury (In collaboration with Professor Kirby). My current collaboration with Professor J Isaacs should also allow me to assess the efficacy of this mutant in rheumatoid arthritis. In addition, I would also like to explore the feasibility of alternative strategies for targeting the chemokine-GAG response including the production of mimetics (Collaboration in place with Dr D.A.Pye, University of Huddersfield), design of an antibody to block GAG epitope etc.
2. Role of glycosaminoglycan-cytokine interaction in epithelial mesenchymal transition: Recent evidence from my work (J Cell Sci, 2003) and others suggest that the specificity of GAG-protein interactions is encoded by the diversity generated by differences in sugar composition and sulfation pattern of the GAG chains. If a certain growth factor is needed the cell could regulate the expression of enzymes (e.g NDST-1) that modify the GAG chain accordingly. Tissue re-modelling is associated with chronic graft rejection. There is evidence of epithelial-to-mesenchymal transition (EMT) and the importance of extracellular matrix (e.g. presentation & activation of TGF-) as a key regulator has been implicated but the mechanism is not defined. It is known that cell surface heparan sulphate, heparaniods have the potential to inhibit the activity of wide range of factors. This includes not only the chemokines, but also VEGF, TGF, fibroblast growth factors, IFN-, histamine, complement, proteases and heparanases.
Based on my recent work on the role of T cell in EMT during chronic allograft rejection ((J Am Soc of Nephrol, 15(2) 390, 2004 & grant funded by National Kidney Research Fund) and track record in the area of cytokine-GAG interaction, I think that I am well positioned to expand my research in to this area. I will be keen to precisely determine a) the requirement of sulphation of HS for binding growth factors leading to fibroblast differentiation and proliferation. b) Identify the key molecular mediators involved in modulation of cell surface HS GAGs during hESC differentiation and c) Provide permissive environment and active signalling cues for guided differentiation (review in preparation on “role of GAGs in chronic allograft rejection” for submission to American Journal of Transplantation)
3. Role of glycosaminoglycan in breast cancer metastasis: In recent years along with my main research I have also been examining the role of chemokine-chemokine receptor interaction in breast cancer metastasis in collaboration with Professor TWJ Lennard. We have established an in vivo model of Breast Cancer metastasis and have shown significantly reduced metastasis in animals treated either with low molecular weight heparin or non-GAG binding chemokines. This successful collaboration has resulted in 2 PhD and I hope to expand this work and seek support from Cancer Research UK or other national funding bodies. The area I would like to concentrate is to define specifically the role of CXCR4 versus CXCR7 (both are receptors for CXCL12) in metastasis /proliferation of cancer cells. A Phase I trial of the CXCR4 chemokine inhibitor AMD 3465 focussed on breast cancer has been proposed for funding by CRUK in collaboration with Hillary Calvert (NICR).
4. Chemokine/chemokine receptors in adult stem cells migration and retention: Increasing evidence suggests that stem cells like metastatic tumour cells use common chemoattractive mechanisms to home to damaged tissue. Responsiveness of stem cells to chemokines may be necessary for the specific homing as well as retention. Chemokines are expressed at the sites of injury e.g. following ischaemia. To utilise adult stem cells in an effective manner in the clinic we need to understand the signalling mechanisms that govern their ability to migrate, proliferate and differentiate. The effects of chemokines and cytokines in regulating cell mobilization and differentiation have already been examined in a number of cell populations. As adult stem cells are rare cell populations the numbers that can be isolated from patients are small. I have joint pilot project with Dr A Meeson on “Role of chemokine receptors in adult stem cells migration”. Based on my experience on chemokine biology I am keen to develop this area with a view to characterise adult bone marrow SP cells in terms of there expression of chemokines and receptors. Additionally, examine their response on exposure to growth factors/chemokines and cytokines. This information will provide us with the means of controlling the behaviour of adult stem cells to allow for ex-vivo expansion of undifferentiated stem cells (grant under preparation for BHF).
5. Role of GAGs in chemokine dependent trophoblast function: Current evidence strongly suggests that chemokines are intimately involved in the maintenance of pregnancy and in parturition. Several chemokines have been implicated as regulators of trophoblast invasion. I have a joint project with Professor S Robson to investigate the influence of CCR1 ligands and their interactions with Glycosaminoglycans on trophoblast invasion. I will be keen to develop this area in collaboration as with my expertise in chemokine–GAG field it provides a unique opportunity to investigate the role of GAGs in chemokine dependent regulation of trophoblast function including invasion.
I currently supervise Post-doctoral Fellow, Research associate, PhD students, MD students and technician. I regularly take Mres and undergraduate project students.
I referee grants regularly from British Heart Foundation, BBSRC etc and have been appointed as examiner (internal/external) regularly for PhD as well as MD thesis. Furthermore, I am also involved in the annual assessment of PhD and MD students within the School/Faculty.
I currently supervise 1 Post-doctoral Fellow, 1 Research associate, 6 PhD students, 3 MD, 1 Technician, Mres project student and regularly take project students from Institute of Cell and Molecular Biosciences. My both the recent project students went on to secure a first in their projects.
· I was awarded special recognition award by Roche Organ Transplantation research Fund for my contribution to research in Transplantation (cash award of 1000 Swiss Francs)-April 2011.
· I am member of the organising team and will be chairing the Transplantation session for British Society of Immunology Summer School, to be held at Newcastle in July 2013.
· Scientific Panels: a) Member of Northern Counties Kidney Research Fund Scientific Sub-Committee. b) Member of Panel of NHS grampian endowment grants.
· Chairing/Arranging a session on chemokines at BSI meeting, Liverpool, December 2010.
· Oral presentation at International HLA and Immunogenetics Conference, Liverpool, 2nd June’2012.
· Oral presentation at American Transplant Congress (April 2011, Philadelphia, USA)
· Invited speaker at School of Biomedical and Natural Sciences, Nottingham Trent University, October 29th, 2010.
· Gordon Conference: Chemotactic Cytokines May 30 – June 4, 2010 at the Il Ciocco Hotel & Resort, Italy, June 2010,
· Oral presentation at 6th International Proteoglycan Conference, Aix-Le-Bains, France, September’ 2009.
· Therapeutic Tolerance Workshop (Invited Speaker for Newcastle showcase), -June, 2009, Newcastle.
· Invited speaker:25th Conference of the European Society for Microcirculation, 26-29 August 2008, Budapest, Hungary.
· Oral presentation at Guy's Hospital, London. 15th February, 2008
· My work has been funded from various National/ International funding bodies (British Heart Foundation, Wellcome, Roche Organ Transplantation Research Fund, MRC, National Kidney Research Fund etc).
· I regularly referee manuscripts for Journal of Biological Chemistry, Biochemical Journal, BBA, etc and am a member of BBC panel for analysis of scientific news related to transplantation/inflammation.
· 4 international and 14 national invited seminars ranging from presentations given to academic institutions, conferences, and scientific meetings during last 5 years.
· (1992-1995): As a Post-doctoral Researcher I single-handedly established the transgenic facility at Newcastle and generated several transgenic lines of mice to address the important issue of protein trafficking. The data generated has been published in peer reviewed journals (Nature Biotechnology 11:376, 1992, Biochemical Journal, 315:857-862, 1996, Gene 202: 203-208, 1997 etc).
· 1990-1992: I was awarded a Commonwealth Post-doctoral Fellowship in Molecular Biology, which is given out only to five candidates every year.
1986-1990: Recipient of National scholarship by Council of Scientific and Industrial Research, India, based on a competitive exam to study for PhD.
During my tenure in Newcastle I have been successful in attracting grant income from national charities and international funding bodies. During current RAE period I have been awarded grants from
. Arthritis Research Campaign (Project grant, £129,000)
• The British Heart Foundation (4 grants, worth £395,256).
• Two International award by Roche Organ Transplant Research Foundation (£242,000).
• The Wellcome Trust (£307,180).
• Leukaemia Research Fund (Joint grant with Durham worth £154,552).
I had earlier forged collaborative links with Serono Pharmaceuticals, Geneva, who are the world leaders in chemokine biology. This resulted in my PhD student purifying the mutants with them. Furthermore, my increased awareness of commercial aspects of research has led to my registering a patent application and we collaborate with Austrian Biotech (ProtAffin).
• PCT/GB2005/002184 (Filing date: 3rd June 2005), non-GAG binding chemokine receptor agonists CCL7, which may be used to treat inflammatory conditions. (Ali S and Kirby JA).
.Inventor on European patent application 07450189.1-2406, SDF-1 based glycosaminoglycan antagonists and method of using same. (Kungl A, Werner, I, Slingsby, J, Ali, S, Kirby, JA).
PGY805 MRes in Medical & Molecular Biosciences (Transplantation Sciences)
BMS 3007: RESEARCH IN BIOMEDICAL SCIENCES (Lecture 4h, course work 2h)
MBBS32 (SSC 1 (A106)
Mres Applied Immunobiology Module/strand (20 credits) (SUR 8014)
I have been a key player (module leader) in designing an Applied Immunobiology module for Mres in Medical and Molecular Biosciences. This module was designed with a view to help us identify able PhD students, Medical students for the Foundation programme and can also be used as the training year in 4year PhD programme. I was aware that there was a lack of choice for students interested in Immunology in the MRes programme. Additionally, there was considerable interest in this field and it also played to our research strengths.
I designed a multi-disciplinary module, drawing upon the specialized expertise and research strengths of academic staff from a number of schools in Faculty of Medical Sciences. The module emphasised on research led teaching which encourages development of analytical and critical thinking and aims to prepare students for research based careers. This module also provides a strong platform for those students aiming to pursue research projects in cellular or molecular immunology.
The success of the module is the fact that in its first year running we have recruited 27 students (usually the top ceiling for the module is 25) and have also managed to get it stranded i.e. people doing their project in this area will be awarded a Mres in Applied Immunobiology. Currently we have 8 students who have taken this strand.