About Professor Nicholas Manolios

To develop a better understanding of auto-immune disorders and to provide alternative treatments to these conditions.

Professor Nicholas Manolios is passionate about his research. His research interests include: (i) Structure and assembly of the T-cell antigen receptor (TCR). In particular, the role of the TCR in the predisposition and causation of auto-immune and inflammatory rheumatic disorders; (ii) Structure-function relationships of T cell assembly and T-cell activation, and how synthetic peptides may be used as therapeutic agents to suppress inflammation in a number of autoimmune conditions including diabetes type I, multiple sclerosis and arthritis; (iii) drug development and drug delivery using nanoparticles; (iv) endocannabinoids and marijuana analogues in the treatment of arthritis; (v) ion channels in the regulation of T-cell activation and function and their inhibition leading to new therapeutic agents; (vi) neuro-immunomodulation.

The most significant research contribution has been to define the structure-function relationships between individual TCR chains and the assembly of the TCR. In 1990 a seminal observation was published that confirmed the importance of transmembrane charges in T-cell antigen receptor assembly (Manolios et al (1990) Science, 249:274-277,) and identified the transmembrane sequence involved in subunit receptor interaction. This paper exemplified how transmembrane regions serve as critical sites for protein-protein/lipid interactions. It also allowed new means to inhibit receptor function. Subsequently the stoichiometry and subunit interactions were defined and published (Manolios et al (1991) EMBO J, 10:1643-1651). Following from these results another important paper showing application was published (Manolios et al (1997) Nature Medicine, 3: 84-87) which described the ability to design and engineer new therapeutic agents based on transmembrane charge interactions and gave "proof of principle" that such an approach was feasible. These observations led us to suggest that targeting intramembrane interactions of the TCR with designed molecules may allow for specific regulation of receptor function. Transmembrane peptides today are a very active area of research with great scientific and commercial potential.

Professor Manolios is Director of Rheumatology Westmead Hospital and Professor in Medicine, University of Sydney. He is involved in clinical service to Westmead Hospital, administration as Head of Department, teaching and research within the department. He is one of only a few leading academic rheumatologists in Australia who has been able to combine basic scientific research with clinical practice and administration. He founded and established research and academic rheumatology at Westmead Hospital. The unit has attracted and trained a number of PhD, Master of Medicine, Honours and a large number of elective overseas students together with volunteer workers. Post-docs from various countries including, England, Germany, China, Sri-Lanka, India, Jordan, Iran and Japan have studied and worked within the unit and have made significant and vital contributions to research. The unit has a vocational rheumatology trainee programme, runs clinical trials and attracts enthusiastic and dedicated doctors from overseas for observer ship and clinical training.

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Selected publications

For a comprehensive list of Professor Manolios's publicatons, please visit his Sydney Medical School profile page.