Vasso Apostolopoulos, PhD Professor


Email: vasso@scientist.com




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     Vasso Apostolopoulos - Research
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1999, Meeting with the Mayor of Athens
The Honorable Mr Dimitris Avramopoulos
1997 Brigadier General Cermony
1996 Premiers Award, with the 
Honorable Mr Jeff Kennett
1997 Brigadier General Ceremony
RESEARCH FUNDING

Fellowships: Recipient of NHMRC CJ Martin Fellowship (4 years); NHMRC R Douglas Wright Biomedical Career Development Award (5 years); Sir Zelman Cowen Cancer Research Fellowship

Research Grants: Recipient of NHMRC Project Grants Australia (5); Australian Research Council (ARC) discovery grant Australia (2); USA Army Breast Cancer Grant USA; Ministry of Research and Technology Grant Greece; National Breast Cancer Foundation Project grant Australia (2); BHP Biliton Corporate Community Program project grant Australia; The Susan G Komen for the Cure project grant USA (2); Cancer Council Victoria project grant; Merck Sharp Dohme project grant; Victoria University industry grant; Victoria University Researcher development grant; Ministry of Education Synergy Program grant Greece. 

Trusts and Foundations: Recipient of grants from, State Trustees (5); Equity Trustees (4); Jamina and Bill Amiet Foundation (2); Scobie and Claire MacKinnon Trust; The Trust Company

Equipment Grants: Recipient of grants from, Wellcome Trust UK; The Eirene Lucas Foundation; The Mazda Foundation, The Harold and Cora Brennen Trust; The Cecilia Kilkeary Foundation (2); Margaret Wolkham; The Eirene Lucas Foundation

Commercial Funding: R&D Syndicate; Prima Biomed Ltd; SciVentures 4G Vaccines; AusIndustry; Vianex SA; ELDrug Ltd

TEACHING AND SUPERVISION

1991-1994,  Prac demonstrator. University of Melbourne, Dept. Anatomy Cell Biology
2002-2007,  Guest Lecturer. RMIT University, 3rd Year Science Students, Bundoora Campus, VIC Australia 
                    (Topics covered - cancer, vaccines)
2002-2007,  Guest Lecturer. RMIT University, Masters in Biotechnology Students, City Campus, VIC Australia 
                    (Topics covered - cancer, vaccines, peptide-MHC-TCR interactions, crystallography)
2006,           Guest Lecturer. School of Molecular Sciences, [Faculty of Science, Engineering and Technology], Victoria University,
                    Australia (Topics covered - crystallography)
2007-2009,  Guest Lecturer. Victoria University, Human Biomedical Sciences, 2nd Year Pathology Nursing Students, St Albans
                    Campus, VIC Australia (Topics covered - Neoplasia)


Supervision of students to completion: 14 PhD, 2 PhD Mentor/Advisor, 3 Masters, 4 BMedSci, 3 BSc(Hons), 2 MD, 4 Internship and 2 vacation scholarship students
Current PhD Students: 4
Supervision of postdocs: 11 
Visiting Professors and Honorary Visiting Professors to the laboratory: 6
Sabbatical Visitors to the laboratory: 2
Clinical Associates to the laboratory: 2 
Supervision of research assistants: 15


Lab personnel and students have received numerous Awards - an indication of the quality of research undertaken by my Students and Postdocs. Some Awards include - 

Lees. C.J., Apostolopoulos, V., Ong, C.S., Xing, P.X., Acres, B., Ramshaw, I., Matthaei, K. and McKenzie, I.F.C. The 5th annual conference of the immunology group of Victoria - New directions in immunological research, Mt Buffalo, VIC Australia, March 1997. Immunotherapy with MUC1 & Cytokines
(Oral presentation, Best Oral Presentation, Book Prize to CJ Lees)

Pouniotis, D.S., Apostolopoulos, V*. and McDonald, C.F*. Thoracic Society of Australia and New Zealand (TSANZ) – Victorian Branch Meeting. Werribee, VIC, Australia, November 2004. (*equal contribution). Alveolar macrophage function is altered in patients with primary lung cancer
(Oral presentation, Best Scientific Award Prize to DS Pouniotis)

Pouniotis, D.S. Travel Grant from Institute of Breathing and Sleep, Austin Health, VIC To attend TSANZ, National meeting, Perth, Australia, 2005.

Katsara, M., Tselios, T., Deraos, S. and Matsoukas, J and Apostolopoulos, V. Peptide Users group, Autumn peptide Symposium. Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC Australia. April 2005. Myelin Basic Protein (MBP), Proteolipid Protein (PLP) Peptides (cyclic and linear, agonist and antagonist): Immune Responses in animal models for Multiple Sclerosis
(Oral presentation and Young Investigator Award to M Katsara)

Pouniotis, D.S., Pietersz, G.A. and Apostolopoulos, V. Brisbane Immunology Group, Sea World, Gold Coast QLD, August 2005. Delivery of tumour antigens and cytotoxic T cell epitopes using a membrane translocating peptide induces cellular and protective immune responses
(Oral presentation and Peter Doherty Scientific Award to DS Pouniotis)

Katsara M,, Tselios T., Deraos S., Deraos G., Matsoukas J. and Apostolopoulos, V. Austin Health Research Week, Heidelberg, VIC Australia, October 2005.
Myelin Basic Protein (MBP) and Proteolipid Protein (PLP) Peptides (linear and cyclic, agonist and antagonist): Immunomodulating Therapeutic Approaches for Multiple Sclerosis (Poster presentation. Highly Commended Poster Award to M Katsara)

Pouniotis, D.S. Cass Foundation Travel Grant, $3,500. To attend. 1st joint meeting of the European National Societies of Immunology (ECI). Paris, France. Sept 2006

Pouniotis, D.S. ASI Postgraduate International Travel Prize. $2,500. To attend, The 2nd International conference on Modern Vaccines adjuvants and delivery systems. The Royal Society of Medicine, London, UK. September 2006.

Pouniotis, D.S. Ian McKenzie Cancer Travel Prize. $3,500. To attend an overseas conference in 2007, Awarded October 2006. The next Intracellular Delivery of Therapeutic Macromolecules: from Concept to Application in Grenoble September 2007.

Sheng, K.C. Ian Jamieson Immunology Travel Prize. $3,500. To attend an overseas conference in 2007, Awarded October 2006. 5th International conference. DC2007 – Dendritic cell vaccination and other strategies to tip the balance of the immune system. Bamberg, Germany. July 2007.

Pouniotis, D.S. NHMRC Peter Doherty Research Fellowship. Australia. Awarded December 2006, begin fellowship June 2008, Research to be undertaken at Department of Pathology, RMIT University Australia.

Katsara, M. Genesis Pharma Travel Award, Greece. To attend the 8th International Conference in Medicinal Chemistry: Drug Discovery and Design Conference. University of Patras, Departments of Chemistry and Pharmacology. Patras, Greece. March 2007

Katsara, M. Multiple Sclerosis International Federation (MSIF) Du Pre Grant, London UK. April 2007. £4,000 for 6 months extension visit for PhD MS project.

Katsara, M. Student Travel Bursary. To attend the 4th International / 7th Australian / 2nd Asia-Pacific Peptide Symposium, Cairns, Qld Australia. AUD$625.

Katsara, M., Deraos, G., Matsoukas, J., Apostolopoulos, V. Austin Health Research Week, Heidelberg, VIC Australia. Oct. 2007. A single or double TCR altered peptide ligands of Myelin Basic Protein (MBP) and Proteolipid Protein (PLP) (Linear and Cyclic) can modulate immune responses in SJL/J mice
(Poster presentation. Finalist - Austhos Travelling Fellowship. Finalist - Ludwig Institute Fellowship)

Pietersz, G.A. and Apostolopoulos, V. Merck and Co Inc / AusBiotech 2007 National Conference. siRNA Delivery Symposium, Brisbane, QLD Australia. October 2007. 
The use of Mannan to deliver polynucleotides (Best Oral presentation, AUD $10,000)

Katsara, M. and Apostolopoulos, V. 9th International Conference in Medicinal Chemistry: Drug Discovery and Design Conference. University of Patras, Patras, Greece. March 2008. Linear/cyclic mutant analogues of self antigens (MBP and PLP) manipulate immune responses in mice (Best Poster Award)

Sheng, K.C. Leukemia Research Fellowship, Keck School of Medicine, University of South California, USA, 2008 (Declined)

Sheng, K.C. Ian McKenzie Cancer Travel Prize. AUD$3,500. To attend an overseas conference in 2009, Awarded October 2008. Keystone Symposia: Dendritic cells. Fairmont Banff Springs, Alberta Canada, March 2009.

Katsara, M. 60th meeting with Nobel Laureates. Lindau, Germany. To attend the Meeting of Nobel Laureates in June 2010. 

Day, S. Multiple Sclerosis International Federation (MSIF) Du Pre Grant, London UK. April 2010. £5,000. To visit Prof Larry Stern Laboratory, University of Massachusetts Medical School for 3.5 months (September - December 2010) to undertake, x-ray crystallography studies of cyclic MBP peptides in complex with human MHC class II, HLA-DR1.

Nelson, K. Cancer Council Victoria Vacation Studentship, Melbourne Australia. Jan-March 2011. AUD$1,500
Project Title: Exploring the chmoprotective potential of selected ethnobotanical plant extracts: Lepidium meyenii (Maca), Spirulina platensis/arthrospira (Spirulina) and Olea europaea (Olive leaf), on human breast cancer cell lines.

Nelson, K. Victoria University Vacation Scholarship, Melbourne Australia. Jan-March 2011. AUD$1,000
Project Title: Exploring the chmoprotective potential of selected ethnobotanical plant extracts: Lepidium meyenii (Maca), Spirulina platensis/arthrospira (Spirulina) and Olea europaea (Olive leaf), on human breast cancer cell lines.

Day, S. Ian Potter Foundation Travel Prize. AUD$2,500. To attend an overseas conference in 2011, Awarded December 2010. Keystone Symposia: New Frontiers at the interface of immunity and glycobiology. Lake Louise, Alberta Canada, March 2011.

Mailins, L.R., Wilkinson, B., Day, S., Apostolopoulos, V. and Payne, R. Royal Australian Chemical Society Symposium, Sydney, NSW Australia, February 2011. Synthesis and biological evaluation of glycopeptides cancer vaccine candidates. (Best Poster Award)
CURRENT RESEARCH INTERESTS





















CANCER VACCINE DEVELOPMENT








MAJOR RESEARCH ACHIEVEMENTS

A. Non Canonical Binding Peptides Peptides to MHC Class I - New Approaches to Vaccine Design


1.   MHC class I, H-2Kb, in complex with, MUC1-8 peptide expressed on adenocarcinomas - x-ray crystal structure. Low affinity peptide  
      binding. Novel peptide design for cancer vaccines. Journal of Molecular Biology, 2002pdf
MUC1 is a high molecular weight glycoprotein overexpressed by adenocarcinomas. We have been using mannan-MUC1 for the selective delivery of MUC1 peptides to the class I pathway. MUC1 peptides are presented by a variety of class I molecules and can generate CTLs. We have described the 9mer epitopes presented by different H-2 class I molecules and by HLA-A2. For the most part, the 9mer peptides have unusual features in that they lack defined anchors and bind with low affinity. Nonetheless, high avidity CTLs are produced. We also noted that MUC1 9mer peptides were not essential as 5-8mer peptides could also bind. In addition to VNTR peptides, several mutations and mimics have been generated. This approach leads to the generation of more powerful anti-MUC1 CTLs. The MUC1 peptides have other novel features. They bind in an unusual fashion, in that the mid and C-terminal regions loop out of the groove more than other peptides and are accessible to MUC1 antibody while the N-terminus is buried. Indeed, MUC1 peptides are the only peptides which are accessible to antibody while in the groove of class I molecules, although other antibodies can react with peptide/MHC molecules or with a MHC dependent configuration. The results clearly indicated that MUC1 is binding in an unusual manner. X-ray structural studies of MUC1 peptide (SAPDTRPA) in complex with MHC class I H-2Kb, demonstrate that the side chains of the amino acids pointing into the pockets are small and the pockets are not completely filled as compared to the high affinity peptide SIINFEKL. This accounts for the low affinity binding of SAPDTRPA peptide to class I. We also have the structure of a peptide SRDHSRTPM, also lacking anchor motifs, but still has high affinity at 25°C, but provids little thermal stability at 37°C. The amino acid arginine at P6 pushes the peptide out of the groove in the central region. The studies demonstrate that peptides do not have to be deeply bound within the groove of Class I molecules, indeed low affinity binding peptides can generate CTLs. Thus, a different mode of peptide binding occurs which may have implications in immunity, and in tolerance induction.
2.    MHC class I, H-2Kb, in complex with, YEA9 peptide (yeastolate). x-ray crystal structure. Novel use of alternative anchor for high 
       affinity binding. Journal of Molecular Biology, 2002pdf
3.    Mutated peptide for high affinity binding, new improved cancer vaccine development, by immunology and x-ray crystallography. 
       Immunology, 2006,  pdf
4.    Use of GalNAc for high affinity binding. Proceedings of the National Academy of Science USA, PNAS, 2003pdf
Designing peptide-based vaccines for therapeutic applications in cancer immunotherapy requires detailed knowledge of the interactions between the antigenic peptide and MHC in addition to that between the peptide-MHC complex and the T cell receptor. Past efforts to immunize with high affinity tumor-associated antigenic peptides have not been very immunogenic, which may be attributed to the lack of T cells to these peptides, having been deleted during thymic development. For this reason, low-to-medium affinity non-canonical peptides represent more suitable candidates. However, in addition to the difficulty in identifying such antigens, peptide binding to MHC and hence its ability to induce a strong immune response is limited. In order to enhance binding to MHC and improve immune responses, anchor modifications of non-canonical peptides would be advantageous. In this study, the non-canonical tumor associated peptide from MUC1, MUC1-8 (SAPDTRPA), was modified at the MHC anchor residues to SAPDFRPL (MUC1-8-5F8L) and showed enhanced binding to H-2Kb and improved immune responses. Furthermore, the crystal structure of MUC1-8-5F8L in complex with H-2Kb was determined and revealed that binding of the peptide to MHC is similar to that of the canonical peptide OVA8. Lazoura and Apostolopoulos et al
Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we reported an immunogenic (in vitro and in vivo) MUC1 glycopeptide (MUC1-8-5GalNAc) bound to H-2Kb, fully cross-reactive with the non-glycosylated variant. Molecular modeling showed that the central P5-Thr-GalNAc residue points into the C-pocket and forms van der Waals and hydrogen bond interactions with the MHC class I. As predicted, GalNAc, modified peptide carrying an additional anchor in the central C anchor pocket, increased the affinity by about 100-fold compared to the native low affinity peptide (MUC1-8). The findings demonstrate, for the first time, that glycopeptides associated with MHC class I molecules can make use of GalNAc to anchor the peptide in the groove and enable high affinity binding.
ALUMNI 


Immunology and Vaccine Laboratory

​Professor Ian McKenzie, 1991-2005, Austin Research Institute, VIC Australia
Dr Catherine Lees, 1994-2000, Victoria University, VIC Australia
Ms Violeta Bogdanovska, 1994-1998, Austin Research Institute, VIC Australia
Ms Julie-Anne Caruana, 1995-1996, Austin Research Institute, VIC Australia
Dr ChinSwee Ong, 1995-2000, The University of Melbourne, VIC Australia
Dr Shari Lofthouse, 1995-1998, Austin Research Institute, VIC Australia
Ms Carla Osinski, 1996-1998, 2001-2003, Austin Research Institute, VIC Australia
Mr Wenjun Li, 2001-2002, Austin Research Institute, VIC Australia
Mr Harry Aletras, 2002-2003, Austin Research Institute, VIC Australia
Ms Jodie Halton (Lodding), 2002-2008, Austin Research Institute, VIC Australia
Dr Anja Scholzen, 2002, Philipps University of Marburg, Germany and RMIT University VIC Australia
Dr Kuo-Ching Sheng, 2003-2010, The University of Melbourne, VIC Australia
Dr Tang Choon Kit, 2003-2008, The University of Melbourne, VIC Australia
Dr Rene Andriessen, 2003-2004, Vrije University Medical Center, Amsterdam, The Netherlands 
Dr Peter VanMaanen, 2003-2004, Vrije University Medical Center, Amsterdam, The Netherlands 
Dr Eliada Lazoura, 2003-2006, Austin Research Institute, VIC Australia
Dr Dodie Pouniotis, 2003-2007, Austin Research Institute, VIC Australia
Ms Myha Huynh, 2004, RMIT University, VIC Australia
Dr Gerben Jan Zandijk, 2005, Vrije University Medical Center, Amsterdam, The Netherlands 
Dr Maria Katsara, 2004-2008, University of Patras, Greece
Ms Roza Nastovska, 2005, RMIT University, VIC Australia
Dr Julie Denoeud, 2006-2007, Ecole Normale de Lyon University, France
Dr Ideke Slaats, 2007, Vrije University Medical Center, Amsterdam, The Netherlands
Dr Nicole Brooks, 2007-2008, Victoria University, VIC Australia
Dr Jennifer Perret, 2006-2010, Austin Health and The University of Melbourne, VIC Australia
Ms Kong Ying Ying, 2009-2010, Monash University, VIC Australia
Dr Stephanie Day, 2008-2011, Burnet Research Institute, VIC Australia
Ms Yvonne Borsetti, 2010, University of Melbourne, VIC Australia, Institute Ranke-Heinemann, Germany
Ms Kristina Nelson, 2010-2011, Victoria University, VIC Australia
Dr Syed Nasir Saeedi Eslami, 2010-2011, Pasteur Institute, Iran.

Visiting
Professor Stamatis Vassilaros, 1997, Prolipsis Medical Center, Greece
Dr Tammy Maxwell, 2003, 2005, Queensland Institute of Medical Research, QLD Australia
Professor Christine McDonald, 2003-2009, Austin Health, VIC Australia
Dr Julie McAuley, 2004, Mater Medical Research Institute, QLD Australia
Professor John Matsoukas, 2005, University of Patras, Greece
Dr Minos Matsoukas, 2005, University of Patras, Greece 
Dr Theodore Tselios, 2005, 2013, University of Patras, Greece
Dr Spiros Deraos, 2005, University of Patras, Greece 
Professor Lily Stojanovska, 2006-2011, Victoria University, VIC Australia
Dr Rabia Ashraf, 2011, Victoria University, VIC Australia 
Dr Mutamed Ayyash, 2011, Victoria University, VIC Australia 
Dr Marilena Androutsou, 2013, ELDrug Ltd, Greece


MUC1 Laboratory and Clinical Trials Laboratory

​Professor Ian McKenzie, 1988-2005, Austin Research Institute, VIC Australia
Professor Pei-Xiang Xing, 1988-2009, Austin Research Institute, VIC Australia
Ms Julie Prenzoska, 1990-1998, Austin Research Institute, VIC Australia
Ms Georgia Poulos, 1996-2000, Austin Research Institute, VIC Australia
Dr Vaios Karanikas, 1995-1998, Austin Research Institute, VIC Australia
Dr LeAnne Hwang, 1995-1998, Austin Research Institute, VIC Australia
Ms Jodie Lodding,  1995-2001, Austin Research Institute, VIC Australia
Mr Julian Pearson, 1995-1998, Austin Research Institute, VIC Australia
CURRENT STUDENTS


2011-Present, PhD Student, Mr Miloud Omar Abobaker, College of Health and Biomedicine, Victoria University, Australia (Co-Supervisor)
Thesis Title: Short Chain Fatty Acids as Immune Modulators in Inflammatory Disorders

2011-Present, Ms Kong Ying Ying, PhD Student, Department of Immunology, Monash University, VIC Australia (Co-Supervisor)
Thesis Title: Role of cancer cells on the immune response

2011-Present, Dr Jennifer Perret, PhD Student, Department of Respiratory Medicine, Austin Health Heidelberg VIC Australia and The University of Melbourne, VIC Australia. LINK
Thesis Title: The epidemiology of lung function in the middle age
2001, with Professor Gordon Ada, ARI Melbourne. 
Sketch by artist, Ms Jane Kempe, Link
2011, Victoria University Research Matters, Kristina Nelson Student, highlight. Click on image.
2004, Inductee Women Honour Roll of Women,  Click on image.
Molecular model of APL peptide MBP85-96 [Y91] in complex with MHC class II H2 I-As. From Katsara and Apostolopoulos et al.,
Schematic representation of MBP83-99 peptide in complex with HLA-DR2. From Katsara and Apostolopoulos et al.,