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Staff Profile

Professor Simi Ali

Professor of Immunobiology

Background

Roles and Responsibilities

I have held senior management responsibilities within the University and Institute and also serve on external Scientific Committees.  For example:

 Faculty Membership

 Member of Faculty Promotion Committee (2015-18)

 Mentor for Faculty Future's Programme (2014-present)

 Member of MRes exam committee. (2007-present)

 Institute of Cellular Medicine Committees

 Inflammation, Immunology & Immunotherapy Theme Co-Lead (March 2019)

 EPSRC CDT-Molecular Sciences for Medicine -Lead for FMS (2019)

 Member ICM EDI committee (2017-present)

 External Committees

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

 Panel Member for National Athena SWAN (Equality Challenge Unit)

Past Membership

 University appointed Governor for Royal Grammar School (2010-2018).

Member of Institute of Cellular Medicine Executive Board (2012-15)

Member of University Senate (2009-2012).

 ICM Post-graduate coordinator (2004-2011).

 ICM Athena SWAN lead (2011-2017)

 Areas of expertise

 Chemokines & their interaction with Glycosaminoglycans

 Inflammation

 Transplantation

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.  Award for Excellence in Science technology and Engineering (Muslim News)-Presented by: Rt Hon Ed Miliband MP, Leader of the Labour Party, London, March 2015.

 2. 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/

3.  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.

4.  Member of Northern Counties Kidney Research Fund Scientific Sub-Committee.

5. Member of panel for ICM Grant Review System.

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

6. Institute of Cellular Medicine was awarded Athena SWAN silver award-June 2013 & 2016 (I was the academic lead for this application).

7. Editorial Board Member for

 ·               Scientific Reports

·                Mediators of Inflammation

           Frontiers in Alloimmunity and Transplantation

    Research

    Research Interests

    My group has a strong background in understanding the mechanisms of tissue damage during transplant rejection with particular emphasis on the chemokine-mediated tissue inflammation. This work is focussed largely on the regulatory interactions between leukocytes, endothelial and epithelial cells.  Within this area, specific interests include the role of chemokines in inflammation, their interaction with cell surface glycosaminoglycans and signal transduction mechanisms mediated by them.

    Current Work:

    1. Regulation of chemokine function during Ischemia-Reperfusion Injury following Transplantation: Following transplantation, the stress due to IRI results in production of chemokines and reactive molecules such as peroxynitrite, which modify the chemokines by nitration. We have shown that nitration of chemokines renders the chemokine non-functional.  This phenomenon could be a natural form of chemokine regulation to prevent excessive inflammation, preventing its detection by conventional methods and therefore limiting the biological relevance of using unmodified chemokines as biomarkers.
    2. Identification of biomarkers in renal fibrosis: Fibrosis is one of the leading hallmarks of chronic allograft dysfunction. Recent evidence indicates that myofibroblasts, could be derived from other cell types including endothelial-to-mesenchymal transition (EndMT). Lineage tracing revealed expression of mesenchymal markers in endothelial derived cells, indicating the presence of EndMT in cardiac fibrosis.  We have identified a microRNA signature of EndMT. Overall, this study provides new insights into the role of microRNA in regulation of endothelial phenotype in relation to fibrosis.
    3. Analysis of tissue re-modelling associated with allograft rejection: Heparan Sulfate (HS) is involved in chronic inflammation and fibrosis development by binding proteins, enhancing their activity and creating chemokine gradients. Our data suggests that HS 3-O-sulfation is modified in fibrosis and highlights HS3ST1 as an attractive biomarker of fibrosis progression with a potential role in HB-EGF signaling.
    4. Examining the role of HLA class I& II antibodies in kidney rejection: Antibody-mediated rejection is one of the major causes of chronic allograft injury. We showed that exposure of endothelial cells to HLA class II antibody induces an activation of signalling cascades characteristic of endothelial cell activation. This activation is further responsible for upregulation of adhesion molecules, which facilitate the interaction of donor endothelium and recipient leukocytes.

    In summary, this programme of work has gone some way towards increasing our understanding of the mechanisms involved in graft rejection and has suggested strategies to increase the survival of transplanted organs. We have also identified potential biomarkers of both IRI and chronic rejection, which could allow transplant patients to be stratified allowing individualized drug treatment.

     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

    21 successful submission for PhD during last 10 years

    I currently supervise 1Research Fellow, 5 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

    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. Scientific Panels: a) Member of Northern Counties Kidney Research Fund Scientific Sub-Committee.
    3. Invited talk at York Medical School (3rd May’2019).
    4. Clinical research fellow I supervise, Emily Thompson, recently won the Leonardo da Vinci award at the European Society of Transplantation. This is the award given to the best oral abstract at the leading European transplant meeting (September 2019, Copenhagen).
    5. Clinical Research Fellow I supervise (Emily Thompson) awarded Medawar Medal at British Transplantation Society Annual Congress 2019.  
    6. I led initiative to set up Transplant Biobank at Newcastle Freeman Hospital (2012-14).
    7. 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).
    8. I regularly referee manuscripts for Journal of Biological Chemistry, Transplantation, Plos one, etc and am a member of BBC panel for analysis of scientific news related to transplantation/inflammation.
    9. 4 international and 14 national invited seminars ranging from presentations given to academic institutions, conferences, and scientific meetings during last 5 years.
    10. (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).
    11. 1990-1992: I was awarded a Commonwealth Post-doctoral Fellowship in Molecular Biology, which is given out only to five candidates every year.
    12. 1986-1990: Recipient of National scholarship by Council of Scientific and Industrial Research, India, based on a competitive exam to study for PhD.

     Current Funding:

    1. MRC, S Ali & A Fisher. Ex-vivo normothermic perfusion of organs to minimise ischemia reperfusion injury. £100,000, (Principal applicant), 9.2019-8.2022

    2. EPSRC, M Waring.  EPSRC Centre for Doctoral Training in Molecular Sciences for Medicine. £6,916,264. (S Ali- Co-applicant and lead for Medical School awarded one studentship in my group~£100,000). 9.2019-8.2026.

    3. NIHR-Blood and Transplant research Unit. (A Fisher & M Nicholson) (3,800,000)  Evaluation of novel approached and technologies to increase the availability of suitable donor organce.10.2015-9.2020.  (S.Ali, investigator of Theme 9).

    4. MRC-Confidence in Concept. N Sheerin & S Ali. Establishing a pig model of ex vivo kidney perfusion to test toxicity and efficacy of therapeutic oligonucleotide therapy. £72,500 (Co-applicant, 2.2019-1.2020

    5. Norther Accelerator CCF. S. Ali & N Sheerin. Evaluation of nitrated-CXL8 to monitor ischaemia reperfusion injury in transplanted kidney. £49,000, S. Ali, Principal applicant .7.2019-6. 2020

    6. British Heart Foundation. H Arthur & S Ali.  Role of endothelial fractalkine in angiogenesis and cardiac injury. £143,000, Co-applicant, 21.1.2019-31.12.2020.

    7. KRUK. (E Thompson). Pre-transplant microRNA blockade using direct Antisense Oligonucleotide delivery during ex vivo normothermic machine perfusion of kidneys. £137,000. I am her supervisor-9.2019-8.2021.

    8. Northern Counties Kidney Research Fund. (S Ali & N Sheerin). Identification and role of microRNAs in renal fibrosis. £25,000, (Principal applicant). 9.2016-9.2019

    9. British Heart Foundation. S Ali & JA Kirby. Post-translation modification of Chemokines during heart transplantation: Implications for their biological function. £105,000, (S Ali, Principal applicant. 1.9.2015-30.9.2018.

    10. EU-MC-IDP. S.Ali. Prolongation of organ survival following transplantation. £1, 200,000. (S Ali, Principal applicant), 1.3.2014-1.3.2018.

    Collaborative links with Industry:

    Cellix, Dublin, microfluidics drug screening tool for examination of adhesion and migration of leukocytes.

    Alamac, Edinburgh, specializes in long chain peptide synthesis.

    XVIVO, Sweden, is the world leading company for solutions used for preservations of lungs before transplantation.

     Patents

    1. 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).
    2. .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).
    Teaching

    Postgraduate Teaching

    Mres Applied Immunobiology of Human Disease (20 credits) MMB8015, Strand leader:  I designed this multi-disciplinary module, drawing upon the specialized expertise and research strengths of academic staff in Medical faculty in 2006. I stepped down from being a Module leader (2009/10) but I have retained the position of strand leader. This involves allocating the project to students stranding in AIB, nominating both external and internal examiners for the dissertation.  Additionally, I give two lectures on the AIB module and also assess the oral presentations. (Marking includes essay, exam scripts and Mres thesis)

    PGY805             MRes in Medical & Molecular Biosciences (Transplantation Sciences) (Lecture 2h, Course work/tutorial 5h)

    Undergraduate Teaching

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

     


    Publications