Dr Grisha Pirianov

Grisha’s research interests are focused on translational medicine: discovering novel drugs and therapeutic targets for pharmacological intervention of inflammatory based diseases.

[email protected]

Background

Grisha obtained his PhD in cancer biology from the National Centre of Oncology Sofia before working as a Fulbright and Wellcome research fellow at Georgetown University Washington DC and Imperial College London, and Lecturer in Clinical Sciences at St Georges University. In 2015, he joined our Department of Biomedical and Forensic Science, where he leads Masters modules in Medical Biotechnology and Professional and Ethical Practice in Industry as part of the Masters course in Biotechnology.

Research interests

Discovery of novel compounds for modulation of Toll like receptor 4 (TLR4) signalling as a strategy for pharmacological intervention of inflammatory-based diseases

Toll-like receptors (TLRs) serve as pattern recognition receptors within the immune system and recognise exogenous ligands in response to inflammatory triggers. Among these receptors, TLR4 is known to play an important role in the process of immune defence. TLR4 has been described to be implicated in inflammatory related diseases supporting the idea that the regulation of TLR4 appears as a potential novel target for treatment. For the last years several TLR4 antagonists have been evaluated in preclinical studies and progressed to clinical trials for treatment of sepsis which have been discontinued in different phases. Therefore the generation of novel TLR4 antagonists is a high challenge with great commercial impact. We have established academic and industrial collaborations with Professor Peri (University of Milan, development of novel mimetic TLR4 antagonists IAXOs compounds), Professor Bennett (Imperial College London, preterm labour and neonatal brain damage), Dr Kammerer (Imperial College London, inflammation in depression) and Innaxon, UK (nano-career technology for delivery of small molecules). The aim of our translational collaborative work is to investigate the mechanisms by which these small novel molecules (IAXOs) can modulate TLR4 signalling and their efficacy for pharmacological intervention of inflammatory based diseases such as atherosclerosis, aneurysm, depression and preterm labour.

Novel hop compounds for treatment of prostate cancer

Polyphenols derived from hop extracts have found applications in the brewing industry to provide both flavour and act as bacteriostatic agents to prevent the brew from spoiling. Lupulone is a β-acids polyphenol found in the hop plant Humulus lupulus that exhibits anti-inflammatory, anti-oxidant and anti-cancer activity.

Prostate cancer is one of the leading causes of cancer deaths in the western world and development of new anticancer compounds which could overcome the resistance of prostate cancer following treatment with existing approaches is a big challenge. Hop-sourced lupulones are natural compounds and they may be suitable candidates for chemotherapy with potentially less toxic side effects. We have established a collaboration with Prof Tyrell (Kingston University), who developed a novel Lupulone derivatives. Current work at our laboratory aims to investigate the potential of these novel Lupulone derivatives for treatment of prostate cancer. Additionally, we examine the mechanisms by which these novel molecules induced different modes of prostate cancer cell death.

Areas of research supervision

• Charys Palmer (PhD student) – Novel small molecules Toll like receptor 4 modulators for treatment of inflammatory-based diseases
• Carol Brosseau (PhD student) –Role of insulin-like growth factor binding protein-3 in 1, 25-dihydroxyvitamin-d 3 -induced breast cancer cell apoptosis
• Dr Petros Mouratidis (postdoctoral researcher) – Novel hop compounds for treatment of prostate cancer

Teaching

BSc (Hons) Biomedical Sciences: Principles of Pathology, Current Advances in Biomedical Sciences, Preparation for Research

MSc Biotechnology: Medical Biotechnology (Module Leader), Professional and Ethical Practice in Industry (Module Leader) and Master Research Projects

Qualifications

• MSc, Molecular Biology, Sofia University, Sofia
• PhD, Cancer Biology, Bulgarian Academy of Sciences, Sofia
• PgCertHE, Health and Biomedical Education, St Georges University London

Memberships, editorial boards

• Academy of Higher Education
• American Heart Association
• European Association of Cell Death
• European Society for Medical Oncology
• Federation of European Biochemical Societies

Research grants, consultancy, knowledge exchange

Collaborative grants in progress

• Industrial and academic collaborative enterprise projects with Prof Cockerill (St Georges University), Prof Peri (University of Milan) studying the efficacy of novel antagonists (Innaxon UK) for modulation of toll like receptor 4 (TLR4) signalling as a strategy for pharmacological intervention of vascular inflammatory based diseases.
• Academic collaborative enterprise projects with Prof Tyrell (Kingston University) on the efficacy of novel hop compounds for treatment of prostate cancer.
• Academic and industrial collaborative project with Dr M Kammerer (Imperial College London) and Sandoz, Switzerland, studying the role of proinflammatory mediators in depression during pregnancy.
• Academic and industrial collaborative project with Dr Kammerer (Imperial College London) and Laboratoires Servier, France, studying the role of the antidepressant Agomelatin on proinflammatory mediators in depression.
• Academic and industrial pilot collaborative project with Prof Bennett (Imperial College London) and Innaxon, UK investigating the role of TLR4 modulators for prevention of neonatal brain damage in preterm labour.

Invited Reviewer

Reviewer for the following journals and funding organisations: ATVB, Atherosclerosis, Cell Death and Differentiation, Archives in Medical Research, Journal of Vascular Surgery, British Journal of Pharmacology, Wellcome Trust, MRC, British Heart Foundation

Selected recent publications

Huggins C, Peri F, Neumann F, Cockerill G and Pirianov G A novel mimetic TLR4 antagonist IAXO-102 inhibits non- haematopoietic TLR4 signalling and prevents aortic aneurysms development, Atherosclerosis, October 242(2):563-70, 2015.

Pirianov G, MacIntyre DA, Lee YS, Waddington S, Terzidou V, Mehmet H, Bennett P. Selective inhibition of TLR4/JNK signaling delays experimental preterm labor and prevents neonatal brain damage. Reproduction, 150(4), 266-277, 2015.

Charolidi N, Pirianov G, Torsney E, Pearce S, Laing K, Nohturfft A and Gillian W Cockerill. Pioglitazone identifies a new target for aneurysm treatment - role of Egr1 in an experimental murine model of aortic aneurysm, Journal Vascular Surgery, 52(2):81-93, 2015.

Mouratidis P, Colston K and Pirianov G Differential role of apoptosis and autophagy associated with anticancer effect of lupulone (hop β-acid) derivatives on prostate cancer cells. Anticancer Agents Medicinal Chemistry, 14(8):1169-78, 2014.

Mouratidis P, Tyrrell E, Tucknott M, Colston K and Pirianov G An investigation into the anticancer effects and mechanism of action of lupulone and its natural and synthetic derivatives in prostate cancer cells. Nutrition and Cancer 65(7) 1086-1092, 2013.

Pirianov G, Torsney E Cockerill GW Diabetes as a negative risk factor for abdominal aortic aneurysm - does the disease aetiology or the treatment provides the mechanism of protection? Curr Vasc Pharmacol 11(3):293-298, 2013.

Pirianov G, Torsney E, Charolidi N, Shoreim A, Gaze D, Petrova S, Laing K, Meisinger T, Xiong W, Baxter BT, et al. Elevation of plasma high-density lipoproteins inhibits development of experimental abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 32(11):2678-2686, 2012.

Pirianov G, Torsney E, Howe F, Cockerill GW Rosiglitazone negatively regulates c-Jun N-terminal kinase and toll-like receptor 4 proinflammatory signalling during initiation of experimental aortic aneurysms. Atherosclerosis 225(1):69-75, 2012.

Recent presentations and conferences

Huggins C, Peri F, Neumann F, Cockerill G and Pirianov G A nano-technology Lipodisq delivery of novel mimetic TLR4 antagonist IAXO-102 modulates in vitro and in vivo non-hematopoietic TLR4 signalling, CLINAM, 28 June-2 July 2015, Basel, Switzerland.

Huggins C, Cockerill G and Pirianov G A novel mimetic TLR4 antagonist IAXO-102 prevents experimental aortic aneurysm development, EAS, Glasgow, March 222-25, 2015.

Pirianov G. Modulators of TLR4 in vasculature. European Congress of Immunology, Satelite symposium, Milan, Italy, August 20-24, 2013.

Pirianov G and Gockerill G. Differential regulation of apoptosis and autophagy by HDL. Gordon Research Conference on Cell Death, Italy, July 20-25, 2012.

Pirianov G, Torsney E, Howe F, Petrova S and Cockerill G. TLR4 signalling in abdominal aortic aneurysms, FAD Annual Meeting, Prague, June 18-19, 2010.

Pirianov G, Torsney E, Howe F, Petrova S and Cockerill G. Possible role of TLR4 signalling in experimental abdominal aortic aneurysms, ATVB Annual Meeting, San Francisco, April 8-10, 2010.

Pirianov G, Torsney E, Howe F, Petrova S and Cockerill G. Activation of JNK signalling in experimental abdominal aortic aneurysms, European Meeting on Vascular Biology and Medicine, Marceille, France, September 17-19, 2009.

Pirianov G, Laux H, Bolton T, Deb R, Torsney E, Thompson M, Cockerill G. Differential gene expression profile following aneurysm formation-effect of Rosiglitazone. Gordon Conference on Matrix Metalloproteinases, Les Diablerets, Switzerland, September 1-4, 2009.

Pirianov G, Holland S, Taylor DL and Mehmet H. Functional TLR4 signalling in microglia and oligodendrocytes. 6th European Conference on Apoptosis, Hauenstein, Germany, June 1-6, 2008.

Pirianov G, Waddington S, Lindstrom, Mehmet H and Bennett PR. A selective JNK inhibitory peptide delays LPS-induced preterm delivery and reduces neuronal brain cell death in the mouse model, 55th SGI Annual Meeting, San Diego CA, March 20-29, 2008.