Professor Simi Ali
Professor of Immunobiology

Roles and Responsibilities

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)

Mentor for Faculty Future's Programme (2014) 

University appointed Governor for Royal Grammar School (2010-present).

Member of Northern Counties Kidney Research Fund Scientific Committee (2011-present)

Member of Institute of Celular Medicine Executive Board (2012-present)

Member of MRes exam committee. (2007-present)

Member of University Senate (2009-2012).

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)

 
Qualifications

1984 BSc Chemistry (1st Class Honours). AMU, Aligarh, India.
1986 MSc Biochemistry (1st Class). AMU, Aligarh, India.
1991 PhD Biochemistry. Central Drug Research Institute, Lucknow, India

Previous Positions

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

Memberships

British Society of Immunology, British Transplantation Society

Honours and Awards

1.  Exhibition at Hatton's gallery on Inspirational Women of North East from 3rd October -20th December, 2013-I have been used as one of the examples. http://www.iwne.org/

2.  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.

3.  Member of Northern Counties Kidney Research Fund Scientific Sub-Committee.
4. Member of panel  for ICM Grant Review System.

5.Regularly review grants for MRC, BBSRC, Cancer Research UK, British Heart Foundation, Wellcome, Asthma UK Foundation and Singapore Biomedical Research Council.


6.Editorial Board Member for “

·         Journal Mediators of Inflammation

·         Journal of Glycobiology

·         Frontiers in Alloimmunity and Transplantation

6. Institute of Cellular Medicine was awarded Athena SWAN silver award-June 2013 (I was the academic lead for this application).


 

Research Interests

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; American Journal of Transplantation, 2010, 10:47-58). 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.

Other Expertise

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.

Current Work

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 Gi-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.

Future Research

Organ transplantation is the treatment of choice for many patients with end-stage diseases. Waiting lists are lengthening but the supply of donor organs has not expanded to meet this demand. Chronic rejection resulting in late loss of graft function now represents the greatest clinical challenge, with many patients rejoining the waiting list years after an initial transplant operation. Indeed, as many as a third of patients joining the kidney transplant waiting list have already chronically rejected one or more previous transplants. Preventing this form of graft loss would have a huge socio-economic impact for patients and transplant medicine. Basic research performed by our group and others has defined this problem but has failed to provide any clinically useful solution. We now believe this solution lies at the interface between basic science and translational medicine, with necessary involvement of the private sector. The POSAT scheme will address this by training a cohort of 4 early stage researchers to function at this dynamic interface in order to address specific problems which contribute to chronic graft failure. This programme will meet two specific objectives: development of methods to reduce organ inflammation immediately after transplantation (thereby preserving long-term graft function), and identification of biomarkers which allow transplant patients to be stratified allowing individualized drug treatment. These complementary objectives will be addressed by allocation of a trainee-specific project to each of the 4 early stage researchers. Although based at Newcastle University, each trainee will spend significant periods working with carefully selected private sector partners and academics at another university in the NorthEast of England. This scheme will produce well qualified translational research scientists who will further our understanding of treatment modalities directed at the Prolongation of Organ Survival After Transplantation.

Research Roles

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.

Postgraduate Supervision

18 successful submission for PhD during last 10 years

I currently supervise 2 Post-doctoral Fellow, 7 PhD students, 1 MD, 1 Technician, Mres project student and regularly take project students from Institute of Cell and Molecular Biosciences. My both the recent Mres project students went on to secure Distinction in their projects.

Esteem Indicators

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 chaired the Transplantation session for British Society of Immunology Summer School, 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.

Oral Presentation at British Society of Transplantation, March (2103).

Transplantomics (Cambridge) April, 2013.

 Invited talk at Aberdeen Medical School (May 2013).

 Keystone Conference on “Chemotactic Cytokines”, 2012, Denver, USA.

 Oral presentation at International HLA and Immunogenetics Conference, Liverpool, 2nd June’2012. 

 PhD student Fatmah Naemi had oral presentation at American Transplant Congress, June 2012, Boston, USA.

 Post-Doc Graeme O’Boyle had oral presentation at Gordon Conference on Chemokines in May’2012, Italy.

 Session chair for therapeutic tolerance workshop, 26-29th June, 2013, Newcastle University.

 I led initiative to set up Transplant Biobank at Newcastle Freeman Hospital (2012-14).

 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.

 Funding

During my tenure in Newcastle I have been successful in attracting grant income from national charities and international funding bodies. My current grants include:

  •  POSAT— Prolong Organ Survival After Transplantation.  FP7-PEOPLE-2013-ITN.  Marie Curie Actions— Initial Training Networks (ITN), Innovative Doctoral Programmes (IDP) (2014-2017)Coordinator: Simi Ali: 1,174,367.26 Euro.
  • Modulation of Wound healing post Myocardial Infarction (PI SA).  Awarded grant from Newcastle special Trustees to generate pilot data (2014-15) (£47,000).
  • Inhibition of CCR7-Mediated Breast Cancer Metastasis using non-Glycosaminoglycan binding chemokine CCL21 (PI: SA) (2013-14). JGW Patterson (£45,000, 2013-14).
  • Role of S1P in ischemia reperfusion injury. The British Heart Foundation (£85,000). (2011-14)


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).

Patents

• 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).

Undergraduate Teaching

PGY805 MRes in Medical & Molecular Biosciences (Transplantation Sciences)


BMS 3007: RESEARCH IN BIOMEDICAL SCIENCES (Lecture 4h, course work 2h)

Postgraduate Teaching

Mres Applied Immunobiology of Human Disease (20 credits)  MMB8015

 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.