Dr Sylwia Ammoun
Profiles

Dr Sylwia Ammoun

Senior Research Fellow

Biomedical Research - Institute of Translational & Stratified Medicine (Plymouth University Peninsula Schools of Medicine and De

Qualifications

EDUCATION AND QUALIFICATIONS

2005

PhD dissertation, Uppsala University, Sweden, Orexin Receptors in Recombinant CHO Cells. Signaling to Short- and Long Term Cells responses

2004

Transfer, Uppsala University, Sweden

1997

Degree of Master of Science, Uppsala University, Sweden Immunomodulatory-and-cytokine gene-cancer therapy

1996

BScs, Uppsala University, Sweden

 

Professional membership

Member of South of England Brain Tumour Alliance (SEBTA)

Teaching interests

TEACHING EXPERIENCE

I enjoy sharing my knowledge and always appreciate teaching in which I have 16 years of experience.

From 1998 to 2005 I taught medical-, pharmacology- and nurse-students at Uppsala University (Sweden) in following subjects: hemodynamics (blood-vascular circulation-system), safety of medical equipment (current), optical refraction of the eye, heart anatomy (dissection), oscilloscope and pacemaker and muscle structure and function. During this time I also supervised undergraduate and BSc biomedical students and lab assistants.

From 2006 until present I have supervised PhD, BSc and undergraduate students in different projects at Peninsula Medical School (Plymouth, UK). Between 2006 and 2007 I have been teaching medical students in “Neurodegenerative disorders” and “Disease prevention and management- vaccines” at the same university.

I completed Problem-based learning (PBL) facilitator and GTA (Graduate Teaching Award) training and I am keen to use obtained knowledge to improve different teaching techniques both in large and small student groups. I believe that the involvement of the students during lectures and seminars is very important as it creates active learning environment. 

TEACHING EDUCATION

2014

Internal and External Doctoral Examiners training

2011

Learning and Teaching for general Teaching Associates (GTA) training including: Theories of Learning and Teaching, Planning Sessions and Delivering Presentations, Learning in Groups, Evaluating Teaching and Giving Feedback, Assessment, Dealing with difficult Situations and Assessment Criteria and Marketing.

2008

Problem-based learning (PBL) facilitator training

 

 

Research interests

RESEARCH INTERESTS AND EXPERIENCE

During my career I have been involved in different projects including: 1) The development of immunomodulatory cancer vaccines to treat Acute Myeloid Leukemia (AML) (Clinical Immunology), 2) Investigation of the role of endogenous retroviruses in Multiple Sclerosis (MS) (Clinical Virology) and 3) Revealing the signalling of orexinergic receptors towards cell fate determination (Neuroscience).

Since January 2006 I have been working at Professor Oliver Hanemann’s laboratory (Plymouth University Peninsula Schools of Medicine and Dentistry, The Institute of Translational and Stratified Medicine). My work has centred on dissecting the signalling pathways involved in the development of Merlin-deficient tumours in order to find specific and effective treatments. I have successfully achieved external funding from four different charities where I was lead or single applicant.  Additionally, I have published nine first authored papers, one book chapter and one invited article in Nature Reviews Neurology. I have also contributed to four other papers published by my colleagues. I am co-supervising a PhD student working on endogenous retroviruses in tumours (Dr Belshaw is the PI) and I am PI for additional PhD students studying the role of the prion proteins and TAM family receptors in the development of Merlin-deficient tumours. Our research team have received an award from Neurofibromatosis (NF) Advocure in recognition of our research and continued commitment to NF2. Additionally, my work within the NF2 field contributed to phase 0 clinical trials at our unit in collaboration with Manchester Hospital. My main goal is to find a good drug treatment for schwannomas and other Merlin-deficient tumours.

Other research

Previous projects

2011-2013:

p53/mouse double minute 2 homolog complex deregulation in Merlin

deficient tumours

This project involved investigation of the role of p53 deregulation in schwannoma development and targeting pathways involved in p53 degradation. In this project I was first author.

Gas6/Axl-family receptors in schwannoma pathological proliferation,  adhesion and survival

In this project we have investigated the role of Axl receptor in schwannoma pathological proliferation, cell-matrix adhesion and survival. In this project I was first and corresponding author.

 

2010-2012:

The role of insulin-like growth factors (IGF1/2) signaling in Merlin-deficient human schwannomas

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates human

schwannoma proliferation, adhesion and survival

In these studies we have demonstrated that IGF1/2 and IGFBP-1 are released from schwannoma cells and IGF-I receptor overexpressed leading to increased schwannoma proliferation and cell-matrix adhesion. In these projects I was first author.

2010-2011: Nilotinib alone or in combination with selumetinib is a drug candidate for

neurofibromatosis type 2

In this project we have tested the therapeutic effectiveness of a PDGFR inhibitor Nilotinib and a MEK1/2 inhibitor selumetinib (AZD6244), in human schwannoma in vitro model. In these projects I was first author.

 

2009-2010: ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma

This project was in collaboration with Dr Karajannis (USA) to test EGFR/HER inhibitor Lapatinib in human schwannoma in vitro model. In these projects I shared first authorship.

 

2008-2009: Targeting ERK1/2 activation and proliferation in human primary schwannoma cells with MEK1/2 inhibitor AZD6244

In this study we have tested the therapeutic effectiveness of a MEK1/2 inhibitor AZD6244, in human schwannoma in vitro model. In these projects I was first author.

 

2007-2008: Dissecting and targeting the growth factor-dependent and growth factor-independent extracellular signal-regulated kinase pathway in human schwannoma

Here we demonstrated that PDGFRβ is strongly overexpressed in schwannoma cells leading to increased schwannoma proliferation. We have also successfully tested a PDGFR/Raf inhibitor Sorafenib. In these projects I was first author.

 

1999-2005: PhD Studentship                                                                                            Orexin Receptors in Recombinant CHO Cells. Signaling to Short- and Long Term Cells responses

The aim of this study was to investigate the mechanisms of orexin receptor coupling to the cascades regulating cell fate and also the assessment of the molecular determinants involved in orexin peptide-orexin receptor interaction.

 

1997-1998: Post PhD research project

Endogenous retroviruses in neurodegenerative diseases

This project focused on the investigation of the expression of the endogenous retrovirus (ERV9)-related proteins in peripheral blood cells and presence in sera from multiple sclerosis (MS) patients.

 

1996-1997: MSc research project

Immunomodulatory-and-cytokine gene-cancer therapy

The aim of this was to design cancer vaccines to treat leukemia and lymphoma. The vaccines would be implemented in both immunotherapy and gene therapy. For immunotherapy, human blood monocytes were separated and differentiated into dendritic cells for antigen presentation and activation of cellular immunity. For cytokine gene therapy, genes for various cytokines were transferred into acute myeloid leukemia (AML) cells via retrovirus- and adenovirus based vectors.

Clinical Research

I am currently involved in phase 0 clinical trials testing Sorafenib and Nilotinib in Neurofibromatosis type 2 (NF2) patients. I perform tests on tumour tissue and blood samples from patients to look for the effect of these drugs on signaling pathways known to be involved in the development of Merlin-deficient tumours.

 

Grants & contracts

RESEARCH GRANTS

Current applications

April 2015      Action on Hearing Loss International project grant

Endogenous Retroviral proteins as potential immunotherapy and/or drug targets for Merlin-deficient tumours treatment and their role in vestibular neuroma development. I am lead applicant for this grant application. Dr. Robert Belshow is co-applicant and Dr. David Hilton collaborator.

March 2015    Breast Cancer Campaign

Endogenous retroviruses as breast cancer immunotherapy targets. I am co-applicant together with Dr. David Hilton. Dr. Robert Belshow is main applicant.

Funding awarded

2014                Action on Hearing Loss Flexi grant, lead applicant, 3 months, £4697

Endogenous Retroviral proteins as potential immunotherapy and/or drug targets for Merlin-deficient tumours treatment and their role in vestibular neuroma development

2014                The Laura Crane Youth Cancer Trust grant, single applicant, 2 years £26,000

The role of prion proteins in Merlin-deficient tumours

TRAVEL GRANTS

2005                Travel grant     Orexins/Hypocretins Symposium, Cologne, Germany

2002               Travel grant European Post Graduate Poster Symposium, Drug Discovery (Pfizer), Sandwich, Kent, UK

2003               Travel grant Neuroscience Meeting, New Orleans, USA

Research groups

Key publications are highlighted

Journals
Articles
Stepanova DS, Semenova G, Kuo Y-M, Andrews AJ, Ammoun S, Hanemann CO & Chernoff J 2017 'An essential role for the tumor suppressor Merlin in regulating fatty acid synthesis' Cancer Research Author Site , DOI PEARL
Provenzano L, Ryan Y, Hilton DA, Lyons-Rimmer J, Dave F, Maze EA, Adams CL, Rigby-Jones R, Ammoun S & Hanemann CO 2017 'Cellular prion protein (PrPC) in the development of Merlin-deficient tumours' Oncogene , DOI PEARL
Zhou L, Lyons-Rimmer J, Ammoun S, Müller J, Lasonder E, Sharma V, Ercolano E, Hilton D, Taiwo I & Barczyk M 2016 'The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin-deficient tumors' Oncogene 35, (26) 3443-3453 , DOI PEARL
Ammoun S, Schmid MC, Zhou L, Hilton DA, Barczyk M & Hanemann CO 2015 'The p53/mouse double minute 2 homolog complex deregulation in merlin-deficient tumours' Mol Oncol 9, (1) 236-248 Author Site , DOI
Ammoun S, Provenzano L, Zhou L, Barczyk M, Evans K, Hilton DA, Hafizi S & Hanemann CO 2014 'Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival' Oncogene 33, (3) 336-346 Author Site , DOI
Widemann BC, Acosta MT, Ammoun S, Belzberg AJ, Bernards A, Blakeley J, Bretscher A, Cichowski K, Clapp DW & Dombi E 2014 'CTF Meeting 2012: Translation of the Basic Understanding of the Biology and Genetics of NF1, NF2, and Schwannomatosis Toward the Development of Effective Therapies' AMERICAN JOURNAL OF MEDICAL GENETICS PART A 164, (3) 563-578 Author Site , DOI
Ammoun S, Provenzano L, Zhou L, Schmid MC & Hanemann CO 2014 'IDENTIFICATION AND TARGETING PATHWAYS INVOLVED IN THE DEVELOPMENT OF MERLIN-DEFICIENT TUMOURS' ANTICANCER RESEARCH 34, (10) 5805-5805 Author Site
Provenzano L, Ammoun S & Hanemann CO 2014 'THE ROLE OF CELLULAR PRION PROTEIN IN SCHWANNOMA AND OTHER MERLIN-DEFICIENT TUMOURS' ANTICANCER RESEARCH 34, (10) 6123-6123 Author Site
Shivane A, Parkinson DB, Ammoun S & Hanemann CO 2013 'Expression of c-Jun and Sox-2 in human schwannomas and traumatic neuromas' HISTOPATHOLOGY 62, (4) 651-656 Author Site , DOI
Ammoun S, Schmid MC, Zhou L, Ristic N, Ercolano E, Hilton DA, Perks CM & Hanemann CO 2012 'Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates human schwannoma proliferation, adhesion and survival' Oncogene 31, (13) 1710-1722 Author Site , DOI
Ammoun S, Schmid MC, Ristic N, Zhou L, Hilton D, Ercolano E, Carroll C & Hanemann CO 2012 'The role of insulin-like growth factors signaling in merlin-deficient human schwannomas' Glia 60, (11) 1721-1733 Author Site , DOI PEARL
Ammoun S, Schmid MC, Zhou L, Ristic N, Ercolano E, Hilton DA, Perks CM & Hanemann CO 2012 'The role of insulin-like growth factors signaling in merlin-deficient human schwannomas. Ammoun S, Schmid MC, Ristic N, Zhou L, Hilton D, Ercolano E, Carroll C, Hanemann CO. Glia. 2012 Nov;60(11):1721-33. doi: 10.1002/glia.22391. Epub 2012 Jul 20' Glia
Ammoun S & Hanemann CO 2011 'Emerging therapeutic targets in schwannomas and other merlin-deficient tumors' Nat Rev Neurol 7, (7) 392-399 Author Site , DOI
Zhou L, Ercolano E, Ammoun S, Schmid MC, Barczyk MA & Hanemann CO 2011 'Merlin-deficient human tumors show loss of contact inhibition and activation of Wnt/β-catenin signaling linked to the PDGFR/Src and Rac/PAK pathways' Neoplasia 13, (12) 1101-1112 Author Site
Ammoun S, Schmid MC, Triner J, Manley P & Hanemann CO 2011 'Nilotinib alone or in combination with selumetinib is a drug candidate for neurofibromatosis type 2' Neuro Oncol 13, (7) 759-766 Author Site , DOI
Ammoun S, Cunliffe CH, Allen JC, Chiriboga L, Giancotti FG, Zagzag D, Hanemann CO & Karajannis MA 2010 'ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma' Neuro Oncol 12, (8) 834-843 Author Site , DOI
Ammoun S, Ristic N, Matthies C, Hilton DA & Hanemann CO 2010 'Targeting ERK1/2 activation and proliferation in human primary schwannoma cells with MEK1/2 inhibitor AZD6244' Neurobiol Dis 37, (1) 141-146 Author Site , DOI
Flaiz C, Ammoun S, Biebl A & Hanemann CO 2009 'Altered adhesive structures and their relation to RhoGTPase activation in merlin-deficient Schwannoma' Brain Pathol 19, (1) 27-38 Author Site , DOI
Ammoun S 2009 'Altered adhesive structures and their relation to RhoGTPase activation in merlin-deficient Schwannoma. Flaiz, Christine; Ammoun, Sylwia; Biebl, Anja; Hanemann, C. Oliver. Brain Pathology, Volume 19, Number 1, January 2009, pp. 27-38(12)'
Flaiz C, Chernoff J, Ammoun S, Peterson JR & Hanemann CO 2009 'PAK kinase regulates Rac GTPase and is a potential target in human schwannomas' Exp Neurol 218, (1) 137-144 Author Site
Ammoun S, Flaiz C, Ristic N, Schuldt J & Hanemann CO 2008 'Dissecting and targeting the growth factor-dependent and growth factor-independent extracellular signal-regulated kinase pathway in human schwannoma' Cancer Res 68, (13) 5236-5245 Author Site , DOI
Ammoun S & Hanemann O 2007 'Strong and long-lasting activation of ERK in human schwannoma cells' Neuropathology and Applied Neurobiology 33, (2) 258-259
Ammoun S, Lindholm D, Wootz H, Åkerman KEO & Kukkonen JP 2006 'G-protein-coupled OX 1 Orexin/hcrtr-1 Hypocretin Receptors Induce Caspase-dependent and -independent Cell Death through p38 Mitogen-/Stress-activated Protein Kinase' Journal of Biological Chemistry 281, (2) 834-842 , DOI
Ammoun S 2006 'G-protein-coupled OX1 orexin/hcrtr-1 hypocretin receptors induce caspase-dependent and -independent cell death through p38 mitogen-/stress-activated protein kinase. Ammoun S, Lindholm D, Wootz H, Akerman KE, Kukkonen JP. J Biol Chem. 2006 Jan 13;281(2):834-42. Epub 2005 Nov 10'
Ammoun S, Johansson L, Ekholm ME, Holmqvist T, Danis AS, Korhonen L, Sergeeva OA, Haas HL, Åkerman KEO & Kukkonen JP 2006 'OX 1 Orexin Receptors Activate Extracellular Signal-Regulated Kinase in Chinese Hamster Ovary Cells via Multiple Mechanisms: The Role of Ca 2+ Influx in OX 1 Receptor Signaling' Molecular Endocrinology 20, (1) 80-99 , DOI
Ammoun S 2006 'OX1 orexin receptors activate extracellular signal-regulated kinase in Chinese hamster ovary cells via multiple mechanisms: the role of Ca2+ influx in OX1 receptor signaling. Ammoun S, Johansson L, Ekholm ME, Holmqvist T, Danis AS, Korhonen L, Sergeeva OA, Haas HL, Akerman KE, Kukkonen JP. Mol Endocrinol. 2006 Jan;20(1):80-99. Epub 2005 Sep 1'
Holmqvist T, Johansson L, Östman M, Ammoun S, Åkerman KEO & Kukkonen JP 2005 'OX 1 Orexin Receptors Couple to Adenylyl Cyclase Regulation via Multiple Mechanisms' Journal of Biological Chemistry 280, (8) 6570-6579 , DOI
Ammoun S 2005 'OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms. Holmqvist T, Johansson L, Ostman M, Ammoun S, Akerman KE, Kukkonen JP. J Biol Chem. 2005 Feb 25;280(8):6570-9'
Ammoun S 2003 'Distinct Recognition of OX1 and OX2 Receptors by Orexin Peptides' Journal of Pharmacology and Experimental Therapeutics 305, (2) 507-514 , DOI
Ammoun S 2003 'Distinct recognition of OX1 and OX2 receptors by orexin peptides. Ammoun S, Holmqvist T, Shariatmadari R, Oonk HB, Detheux M, Parmentier M, Akerman KE, Kukkonen JP. J Pharmacol Exp Ther. 2003 May;305(2):507-14. Epub 2003 Jan 24'
Kukkonen JP, Holmqvist T, Ammoun S & Akerman KEO 2002 'Functions of the orexinergic/hypocretinergic system' AJP: Cell Physiology 283, (6) C1567-C1591 , DOI
Ammoun S 2002 'Functions of the orexinergic/hypocretinergic system. Kukkonen JP, Holmqvist T, Ammoun S, Akerman KE. Am J Physiol Cell Physiol. 2002 Dec;283(6):C1567-91. Review. Erratum in: Am J Physiol Cell Physiol. 2003 Apr;284(4)'
Nasman J, Kukkonen JP, Ammoun S & Akerman KE 2001 'Role of G-protein availability in differential signaling by alpha 2-adrenoceptors' Biochem Pharmacol 62, (7) 913-922 Author Site
Ammoun S 2001 'Role of G-protein availability in differential signaling by alpha 2-adrenoceptors. Nasman J, Kukkonen JP, Ammoun S, Akerman KE. Biochem Pharmacol. 2001 Oct 1;62(7):913-22'
Ammoun S 2000 'Recombinant expression of a selective blocker of M(1) muscarinic receptors. Näsman J, Jolkkonen M, Ammoun S, Karlsson E, Akerman KE. Biochem Biophys Res Commun. 2000 May 10;271(2):435-9'
Näsman J, Jolkkonen M, Ammoun S, Karlsson E & Åkerman KE 2000 'Recombinant Expression of a Selective Blocker of M1 Muscarinic Receptors' Biochemical and Biophysical Research Communications 271, (2) 435-439 , DOI
Olsson P, Ryberg B, Awad R, Ammoun S, Yin H, Hjalmarsson S & Blomberg J 1999 'Retroviral RNA Related to ERV9/MSRV in a Human Serum: A New Sequence Variant' AIDS Research and Human Retroviruses 15, (6) 591-593 , DOI
Ammoun S 1999 'Retroviral RNA related to ERV9/MSRV in a human serum: a new sequence variant. Olsson P, Ryberg B, Awad R, Ammoun S, Yin H, Hjalmarsson S, Blomberg J. AIDS Res Hum Retroviruses. 1999 Apr 10;15(6):591-3'
Ammoun S, Cunliffe CH, Allen JC, Chiriboga L, Giancotti FG, Zagzag D, Hanemann CO & Karajannis MA 0 'ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma' Neuro-oncology Publisher Site , DOI PEARL
Chapters
Hanemann CO & Ammoun S 2010 'Receptor tyrosine kinases in human schwannoma' Angiogenesis & Therapeutic Targets In Cancer 90-98 , DOI
Conference Papers
Hilton D, Shivane A, Kirk L, Ammoun S & Hanemann CO 2014 'Growth factor signaling pathway activation in meningiomas' 101-101
Hilton DA, Shivane A, Turner L, Ammoun S & Hanemann O 2013 'Activation of multiple signalling pathways in meningiomas is unrelated to NF2 gene status' 35-35
Shivane A, Ammoun S, Parkinson DB & Hanemann CO 2012 'EXPRESSION OF C-JUN & SOX-2 IN HUMAN SCHWANNOMAS AND TRAUMATIC NEUROMAS' 9-10
Zhou L, Ercolano E, Ammoun S, Schmid MC, Barczyk M & Hanemann CO 2012 'MERLIN DEFICIENT HUMAN TUMOURS SHOW LOSS OF CONTACT INHIBITION, ACTIVATION OF WNT/beta-CATENIN SIGNALING LINKED TO THE PDGFR/SRC AND RAC/PAK PATHWAYS' 5-6
Ammoun S, Zhou L, Barczyk M, Hilton D, Hafizi S & Hanemann CO 2011 'GAS6/AXL-FAMILY RECEPTORS IN SCHWANNOMA PATHOLOGICAL PROLIFERATION, ADHESION AND SURVIVAL' 1-1
Hanemann CO, Ammoun S, Schmid MC, Ristic N, Ercolano E & Zhou L 2010 'IGF/IGFBP SIGNALING IN MERLIN-DEFICIENT TUMORS' 22-22
Schmid MC, Zhou L, Ammoun S & Hanemann CO 2010 'Targeting focal adhesion kinase (FAK) in primary human schwannoma' 42-42 , DOI
Hanemann CO & Ammoun S 2009 'MERLIN'S TUMOURS: FROM BENCH TO BEDSIDE' , DOI
Mackay L, Higgins S, Abderrahim A, Mistry P, Ammoun S, Whitaker G, Akinwunmi J, Hanneman CO & Pilkington GJ 2008 'IGF-BP1/2 expression in histological sections, biopsy-derived cell cultures and cyst fluids from nervous system neoplasms' 21-21
Ammoun S & Hanemann O 2007 'Strong and long-lasting activation of ERK in human schwannoma cells' 258-259