hossein-ashrafi
Hossein Ashrafi, PhD
Associate Professor of Pathology

Education

1994-1998 PhD in Pathology/Cancer Biology Beatson Institute for Cancer Research, Faculty of Medicine, University of Glasgow, UK
1983–1989 Doctor of Veterinary Medicine (DVM) University of Tehran, Tehran, District 16, Azar St، Enghelab Square, Iran

Biography

Dr. Hossein Ashrafi obtained his PhD from Beatson Institute for Cancer Research, University of Glasgow in 1998 where he worked on viral causes of cancer. In the same year he was offered a postdoctoral fellowship in the Medical Oncology Laboratory at Glasgow University’s Medical School, he was awarded a Royal Society Developing World Study Visit fellowship for distinguished postdoctoral work on relationship between papillomavirus and immune response.

Dr. Hossein Ashrafi joined Kingston University, London in 2009 where he is currently an Associate Professor / Reader in Pathology, Course Leader for MSc Cancer Biology, fellow of Institute of Biomedical Science (IBMS), Fellow of Higher Education (FHEA). Dr. Hossein Ashrafi teaches on a range of Medical Science modules, supervise PhD research students, and lead an active research group on the interactions between the human host, viral pathogen and cancer, and also therapeutic approaches toward Human Papillomavirus (HPV) related cancers.

Over the past eighteen years, he was responsible for the delivery of different projects in the areas of biomedical sciences with a particular interest in investigating “association of Human Papillomavirus (HPV) and cancers” and also studying mechanisms of immunomodulation by Papillomavirus.

An important development in his career was collaborative work with Professor Campo of Glasgow University where they were the first to experimentally demonstrate that E5 oncoprotein of papillomavirus down-regulates MHC-I, therefore, potentially capable of evading killing by cytotoxic T lymphocytes and by natural killer cells. This helped the development of biomedical sciences in general, animal and human research in particular. This has lead to several publications in international journals and was the basis for awards and funding applications to further pursue the long-term aspects of the projects and to initiate new investigation.

Current research and future activities: Dr. Hossein Ashrafi have several goals to accomplish in the near future and some long term. He is currently leading an active research programme with focus on the following subjects below:

a) Association of Human Papillomavirus (HPV) and Breast Cancer (BC)

Studies on HPV role in breast carcinogenesis have generated controversy and it is still not clear whether HPV is present in breast tumours. Following successful ethical and R&D approval, our preliminary results have shown the first ever evidence for the presence of HPV viral DNA in freshly obtained human breast cancer tissue and now provides a solid basis to advance research in a crucial health priority affecting women.

Our current early findings strengthen the association of HPV and breast cancer and will allow us to address important questions on the causative agents of breast cancer. The knowledge acquired will lead to better understanding of risk factors other than those established to date. Cancer prevention, viral carcinogenesis and breast cancer are rapidly developing sectors of this field and the prospect of investigating the use of vaccines to prevent cancer is very appealing.

b) Association of Human Papillomavirus (HPV) and Cervical Cancer.

Despite the medical importance and high incidence rate of cervical cancer, there is lack of information on the incidence of HPV genotypes and their distribution in cervical cancer patients which we plan to investigate in patients with Cervical Cancer in different populations. This collaborative study suggests a potential need for a broad–spectrum, prophylactic vaccine capable of protecting against the many other HPV types, as current vaccines (GSK & Merck) are type restricted to HPV 16 & 18. Our current investigation on distribution of HPV genotypes in cervical tumor tissue of patients revealed the presence of HPV 45 and HPV 39 in patients with cervical cancer and there is good evidence for generating a new broad spectrum prophylactic vaccine. The published findings in “Infectious Agents and Cancer” allow further investigations of HPV genotyping in the wider populations in UK and developing countries.

c) Association of Varizella-Zoster-Virus (VZV) gene ORF 1 and host immune response.

VZV causes chicken pox (Varicella) primary infection which becomes latent in the dorsal root ganglia and trigeminal ganglia, and may reactivate to cause shingles, the most serious complication of which is post-herpetic neuralgia occurring in ~ 50% of individuals over 60 yrs. Severity of lesions depends on the host’s immune response.

Like many viruses, VZV appears to have evolved escape mechanisms from host immune surveillance by down-regulating cell surface MHC 1 expression which delays the resolution of infection. VZV genome encodes a membrane gene, ORF 1, that is localised in plasma membrane and cell Golgi apparatus, and is possibly important for MHC class I transport to the cell surface. This project seeks to identify active mechanisms operated by viral proteins to allow the virus to persist and progress to PHN.  This study aims to investigate the association between ORF 1 gene and MHC 1 transport to the cell surface.

The study outcome will be a valuable attempt to elucidate factors involved in VZV related lesion progression, contribute to existing knowledge and importantly allude to further investigations of this virus on the biology of the disease.

d) Inhibition of immune system through Human papillomavirus (HPV) E5 protein.

Our previous findings of MHC-1 down-regulation by HPV E5 oncoprotein and their effect on evasion by cytotoxic T lymphocytes would be interesting to pursue with siRNA technology if resources are available.

Research Interests

  1. Association of Human Papillomavirus (HPV) and Breast Cancer (BC)
  2. Association of Human Papillomavirus (HPV) and Cervical Cancer
  3. Therapeutic approaches toward Human Papillomavirus (HPV) related cancers
  4. Association of Varizella-Zoster-Virus (VZV) gene ORF 1 and host immune response
  5. Association of human papillomavirus (HPV) and Urinary system cancers (Prostate, Bladder and Renal)

Scientific Activities

Teaching Experience
2013-Present Associate Professor / Reader in Pathology, Kingston University London, Penrhyn Rd, Kingston upon Thames, UK
2009-2013 Lecturer/Senior Research Fellow, Institute of comparative Medicine, University of Glasgow, AND Research Manager, Strathclyde University & NHS Education for Scotland
2000-2003 Research Fellow, Institute of comparative Medicine, University of Glasgow, UK
1998-2000 Postdoctoral Research Fellow, Department of Medical Oncology, University of Glasgow, UK
1989-1994 Lecturer in Pathobiology, University of Mazandaran, Iran
Professional Activities
  • Team leader in Race equality charter mark activity, SAT Composition,  Kingston University
  • Mentor: Beyond Barriers Staff Mentoring scheme mentoring a senior lecturer – Faculty of Arts and Social Sciences (FASS)
  • Course leader and Admission tutor for Cancer Biology
  • NIHR Grant reviewer-  Currently (July 2016) reviewed a grant of £1, 250,000.000 on HPV related cancer treatment
  • Editorial Board member of journals

MEMBERSHIP OF PROFESSIONAL BODIES

  • 2010-present: Fellow of the Higher Education Academy (UK) – Recognition Reference: 42347
  • 2013-present: Fellow of the Institute of Biomedical Science

Honors & Awards
2017-2018 Medical Research Centre, HMC Doha-Qatar Grant - Association of high risk HPVs and Breast Cancer in population of Qatar
2015-2016 IBMS Research Grant. An investigation on the association of high risk HPVs and Breast Cancer
2015 Rose Award Winner for Exceptional Contribution to the Community/Environment –“The Race Equality Charter Mark”
2014 Best Teacher of Postgraduates Winner, Student-led Learning and Teacheing Award and Student Voice and Support Awards, Kingston University London, Penrhyn Rd, Kingston upon Thames, UK
2014-2015 IBMS Research Grant. An investigation on the association of high risk HPVs and Breast Cancer
2013-2014 Collaborative Research Grant from King Fahad Medical City Research and Enterprise, Saudi Arabia – “The association of Human Papillomavirus (HPV) and Cancer
2013 SEC Faculty, Kingston University-QR funding for Allied Health"-Cancer theme - purchase of TissueLyser LT for HPV and Breast Cancer Research
2012 SEC Faculty, Kingston University award for study on HPV and breast cancer
2005 Best poster in Celsus Research Group Meeting, West of Scotland Science Park
2004 Best poster in Celsus Research Group Meeting, West of Scotland Science Park
2002-2006 Medical Research Council (MRC) grant – Co-applicant, -“the role of E5 protein of papillomavirus in cell transformation and immune evasion
2000 Royal Society Developing World Study Visit Award fellowship

Publications

  1. Aziz Salman N, Davies G, Majidy F, Shakir F, Akinrinade H, Perumal D, Ashrafi G.H (2017) Association of High Risk Human Papillomavirus and Breast cancer: A UK based Study. Scientific Reports – Nature. 27;7:43591.
  2. Amjadi O, Rafiei A, Haghshenas M, Navaei RA, Valadan R, Hosseini-Khah Z, Omran AH, Arabi M, Shakib RJ, Mousavi T, Ashrafi GH (2016) A systematic review and meta-analysis of seroprevalence of varicella zoster virus: A nationwide population-based study. J Clin Virol. 87:49-59.
  3. Ashrafi GH and Perumal D (2015) Human Papillomavirus and Cancer – Immunological consequences of MHC Class I Down-Regulation. Int Biol Biomed J., 1, 1-8
  4. Motamed N, Perumal D, Zamani F, Ashrafi H, et al (2015) Conicity Index and Waist-to-Hip Ratio Are Superior Obesity Indices in Predicting 10-Year Cardiovascular Risk Among Men and Women. Clin Cardiol. 9: 527-34
  5. Keyvani H, Sohrabi M, Zamani F, Poustchi H,  Ashrafi H, et al (2014) A Population Based Study of Hepatitis B Virus in Northern Iran, Amol. Hepat Mon.
  6. Ghaffari J. Ashrafi H, Ranjbar AR, Nazari Z (2014) Vitamin E in children with asthma: A review.  Pediatr Rev. 2: 57-65.
  7. Haghshenas MR, Golini-moghaddam T, Rafiee A, Emadeian O, Shykhpour A, Ashrafi GH (2013). Prevalence and type distribution of high-risk human papillomavirus in patients with Cervical Cancer: A population-based study. Infectious Agents and cancer. 8:20
  8. P.G.E. Kennedy, P. Montague, F. Scott, E. Grinfeld, G.H. Ashrafi, J. Breuer, E. G. Rowan (2013) Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line. PLoS One 8 (1)
  9. Ashrafi GH, Grinfeld E, Montague P, Forster T, Ross A, Ghazal P, Scott F, Breuer J, Goodwin R, Kennedy PG (2010). Assessment of transcriptomal analysis of Varicella-Zoster-virus gene expression in patients with and without post-herpetic neuralgia. Virus Genes. 41, 192-201.
  10. Campo MS, Graham SV, Cortese MS, Ashrafi GH, Araibi EH, Dornan ES, Miners K, Nunes C, Man S (2010). HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology. 407, 137-42.
  11. Cortese MS, Ashrafi GH, Campo MS (2010). All 4 di-leucine motifs in the first hydrophobic domain of the E5 oncoprotein of human papillomavirus type 16 are essential for surface MHC class I downregulation activity and E5 endomembrane localization. Int J Cancer. 126, 1675-82.
  12. Barbaresi S, Cortese MS, Quinn J, Ashrafi GH, Graham SV, Campo MS (2010). Effects of human papillomavirus type 16 E5 deletion mutants on epithelial morphology: functional characterization of each transmembrane domain. J Gen Virol. 91, 521-30.
  13. Ashrafi GH, Piuko K, Burden F, Yuan Z, Gault EA, Muller M, Trawford A, Nasir L and Campo MS (2008). Vaccination of sarcoid-bearing donkeys with chimeric virus-like particles of Bovine Papillomavirus type 1. Journal of General Virology, 89: 148-157
  14. Araibi EH,  Marchetti B, Dornan E, Ashrafi G.H, Dobromylskyj M, Ellis SA, Campo MS (2006). The E5 oncoprotein of BPV-4 does not interfere with the biosynthetic pathway of non-classical MHC class I. Virology, 353, 174-83.
  15. Ashrafi GH, Haghshenas MR, Marchetti B, and Campo MS (2006). The E5 protein of Human Papillomavirus type 16 HLA class I and interacts with the heavy chain via its first hydrophobic domain. International Journal of Cancer,119, 2105-12.
  16. Babamahmoodi F, Aghabarari F, Arjmand A, and Ashrafi G.H. (2006) Three rare cases of anthrax arising from the same source. Journal of Infection, 53, 175-179.
  17. Ashrafi GH, Brown D, Fife KH and Campo MS (2006) Down-regulation of MHC class I is a property common to papillomavirus E5 proteins. Virus Research, 120, 208-11.
  18. Marchetti B, Ashrafi G.H, Dornan E, Araibi EH, Ellis SA, Campo MS (2006) The E5 protein of BPV-4 interacts with the heavy chain of MHC class I and irreversibly retains the MHC complex in the Golgi apparatus. Oncogene, 25, 2254-2263.
  19. Tsirimonaki E, Ullah R, Marchetti B, Ashrafi G.H, McGarry L, Ozanne B, Campo M.S (2005). The papillomavirus E5 oncoprotein interferes with the actin cytoskeleton and focal adhesions. Virus Research, 115, 158-168. 
  20. Ashrafi GH, Haghshenas MR, Marchetti B, O’Brien P, Campo MS (2005). The E5 protein of Human Papillomavirus type 16 selectively down-regulates surface HLA class I. International Journal of Cancer, 113, 276-283.
  21. Araibi EH, Marchetti B, Ashrafi GH, and Campo MS (2004). Down-regulation of MHC class I in bovine papillomas. Journal of General Virology, 85, 2809-14
  22. Marchetti B, Ashrafi G.H, Tsirimonaki E, O’Brien PM and Campo MS (2002) The bovine papillomavirus oncoprotein E5 retains MHC class I molecules in the Golgi apparatus and prevents their transport to the cell surface. Oncogene, 21, 7808-7816.
  23. Ashrafi G.H, Tsirimonaki E, Marchetti B, O’Brien PM, Sibbett GJ, Andrew L and Campo MS (2002) Down-regulation of MHC class I by papillomavirus E5 oncoproteins. Oncogene 21, 248-259.
  24. Ashrafi G.H., Pitts J.D., Faccini A.M., McLean P., O’Brien V., Finbow M.E.  & Campo M.S. (2000). Binding of BPV-4 E5 (E8) to 16k ductin, down-regulation of gap junctional intercellular communication and cell transformation are independent events. Journal of General Virology, 81, 689-694
  25. O’Brien, V., Ashrafi G.H., Grindlay G.J., Anderson R. & Campo M.S. (1999). A mutational analysis of the transforming functions of the E5 (E8) protein of BPV- 4. J Virol, 255, 385-394
  26. Faccini, A.M., Cairney, M., Ashrafi, G.H., Finbow, M.E., Campo, M.S. & Pitts, J.D. (1996).  The bovine papillomavirus type 4 E5 (E8) protein binds to ductin and causes loss of gap junctional intercellular communication to primary fibroblasts. J Virol, 70, 9041-5.

     
Journal of Breast Cancer Research and Advancements