Laboratory Head
Associate Prof. Frank Alderuccio
Email: frank.alderuccio@monash.edu
Phone: (03) 99030281
Department of Immunology
Room 2U26
Monash University
Level 2, AMREP Building
Melbourne 3004 Victoria,
AUSTRALIA
Staff List
PhD Student:
Zeyad Nasa
Amit Joglekar
Jie-Yu Chung
Cai Zhang
Biography
Associate Professor Frank Alderuccio completed his undergradate honours degree at Monash University in 1982. After completing a PhD in Immunology he spent two years as a post-doctoral fellow at the Scripps Research Institute in La Jolla, California where he continued his interest in autoimmunity. On returning to Australia in 1991, he joined the Department of Immunology as a research fellow and developed an interest in immune tolerance and its critical role in autoimmunity. He has maintained this interest to current studies that are focused on experimental strategies that can be used in a clinical setting to promote antigen specific tolerance through genetic manipulation of the bone marrow compartment. This revolves around the concept gene therapy can be used to promote immunological tolerance and that this may be used in a clinical setting to treat autoimmunity. In 2002, A/P Alderuccio was appointed as a Senior lecturer within the Dept of Immunology and promoted to Associate Professor in 2007. Together with his research, A/P Alderuccio has a major role in the Immunology teaching program undergraduate and honours students and is the post-graduate coordinator for the department.
Research Interests
Autoimmune diseases are a major health problem and defined by an immune response that targets self-tissues leading to clinical illness. It affects up to 5% of the population and includes common diseases such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis. The underlying basis of autoimmunity is a pathogenic immune response that attacks tissues of our own body. A major interest of our laboratory is understanding the processes associate with the autoimmune response and loss of immunological tolerance with the aim of devising strategies to prevent or reverse autoimmunity. It is known that exposure of the developing immune system to self-antigens is important for induction of tolerance and we have demonstrated in experimental mouse models of autoimmunity that ectopic expression of a defined autoantigen can induce immune tolerance and render mice resistant to disease induction. Clinical relevance is realised through the observation that this tolerance can also be transferred through the bone marrow compartment. This opens the door to suggest that genetic manipulation of normal bone marrow stem cells leading to ectopic expression of autoantigens can be used to induce immune tolerance and incorporated in a strategy to treat autoimmunity. Our most recent work has indeed shown this and using an animal model for multiple sclerosis called experimental autoimmune encephalomyelitis (EAE), we have shown that a gene therapy approach that targets the bone marrow compartment can promote immune tolerance and disease resistance. Of more relevance however, we have also shown that this approach can be utilised in the EAE model to treat established disease that would be more relevant in terms of human disease. Our work is focused on understanding the mechanisms involved in these observations and new strategies that could be developed to treat autoimmunity in a disease specific manner.
Projects
Honours and Post-graduate studies
The research directions of the laboratory are focused on understanding the mechanisms associated with tolerance induction associated with the transfer of genetically manipulated bone marrow cells and devising new strategies to promote tolerance in the context of autoimmune disease. A general over
Students wishing to pursue post-graduate studies may have the opportunity to secure study scholarships
Interested students should talk with A/P Frank Alderuccio (frank.alderuccio@monash.edu) for further details
Publications
(Alderuccio, Chan et al. 2010; Ko, Kinkel et al. 2010; Chen, Chan et al. 2011; Hosseini, Oh et al. 2011; Ko, Chung et al. 2011; Nasa, Chung et al. 2012; Siatskas, Seach et al. 2012)
Alderuccio, F., J. Chan, H. J. Ko, J. Y. Chung, Z. Nasa and B. H. Toh (2010). "A molecular Trojan horse: hijacking the bone marrow to treat autoimmune diseases." Discov Med 9(49): 512-518.
Chen, X. T., S. T. Chan, H. Hosseini, D. Layton, R. Boyd, F. Alderuccio, B. H. Toh and J. Chan (2011).
"Transplantation of retrovirally transduced bone marrow prevents autoimmune disease in aged mice by peripheral tolerance mechanisms." Autoimmunity 44(5): 384-393.
Hosseini, H., D. Y. Oh, S. T. Chan, X. T. Chen, Z. Nasa, H. Yagita, F. Alderuccio, B. H. Toh and J. Chan (2011). "Non-myeloablative transplantation of bone marrow expressing self-antigen establishes peripheral tolerance and completely prevents autoimmunity in mice." Gene Ther.
Ko, H. J., J. Y. Chung, Z. Nasa, J. Chan, C. Siatskas, B. H. Toh and F. Alderuccio (2011). "Targeting MOG expression to dendritic cells delays onset of experimental autoimmune disease." Autoimmunity 44(3): 177-187.
Ko, H. J., S. A. Kinkel, F. X. Hubert, Z. Nasa, J. Chan, C. Siatskas, P. Hirubalan, B. H. Toh, H. S. Scott and F. Alderuccio (2010). "Transplantation of autoimmune regulator-encoding bone marrow cells delays the onset of experimental autoimmune encephalomyelitis." Eur J Immunol 40(12): 3499-3509.
Nasa, Z., J. Chung, J. Chan, B. T. Toh and F. Alderuccio (2012). "Non-myeloablative conditioning generates autoantigen-encoding bone marrow that prevents and cures an experimental autoimmune disease." American Journal of Transplantation Accepted for publication.
Siatskas, C., N. Seach, G. Sun, A. Emerson-Webber, A. Silvain, B. H. Toh, F. Alderuccio, B. T. Backstrom, R. L. Boyd and C. C. Bernard (2012). "Thymic Gene Transfer of Myelin Oligodendrocyte Glycoprotein Ameliorates the Onset but Not the Progression of Autoimmune Demyelination." Mol Ther.
Alderuccio, F., J. Chan, D. W. Scott, and B. H. Toh. 2009. Gene therapy and bone marrow stem-cell transfer to treat autoimmune disease. Trends Mol Med 15:344-351.
Chan, J, Ban, E.J., Chun, K.H., Wang, S., Backstrom, T., Bernard, C., Toh, B.H. and F. Alderuccio 2008, Transduced bone marrow establishes antigen-specific deletional tolerance in experimental autoimmune encephalomyelitis. J. Immunology, 181(11): 7571-7580
Chan, J, Ban, E.J., Chun, K.H., Wang, S., Mcqualter, J., Bernard, C., Toh, B.H. and F. Alderuccio. 2008 Methylprednisolone induces reversible clinical and pathological remission and loss of lymphocyte reactivity to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. Autoimmunity, 41(5), 405-413
Alderuccio, F. Chan, J and Toh, B.H. 2007 Haematopoietic stem cell based gene therapy as a strategy to treat autoimmune disease. Advances in Gene, Molecular and Cell Therapy 1(2), 141-149
Chan, JM, Clements, WJ, Field, J, Nasa Z, Lock P. Yap F, Toh BH and F. Alderuccio. (2006). Transplantation of bone marrow engineered to express proinsulin2 establishes molecular chimerism and prevents insulitis in the NOD mouse model of T1D, J Gene Med, 8, 1281-1290
Biondo, M, Field, J., Toh, B.H. and F. Alderuccio (2006) Prednisolone treatment of experimental autoimmune gastritis in athymic mice promotes gastric regeneration and long-term remission. J Pathology, 209, 384-391
Alderuccio F, Siatskas C, Chan J, Field J, Murphy K, Nasa Z and Toh BH, (2006), Haematopoietic stem cell gene therapy to treat autoimmune disease. Current Stem Cell Reviews, 1, 231-238
