Genes associated with inflammatory diseases

As Deputy CEO and Target Manager for the CRC for Chronic Inflammatory Diseases, my laboratory collaborates very closely with Prof. D. Hume. The aim of my lab within the CRC for Chronic Inflammatory Diseases is to identify genes that are aberrantly expressed during chronic inflammation, to identify the function of unknown genes, and to set up assays for the analysis of these genes in vitro and in vivo. Each candidate target is intensely investigated for its presence in human disease and its function in inflammatory cells, a process known as target validation. Once these genes have been fully validated as targets in chronic inflammatory diseases they are integrated into the drug development pipeline of our industrial partners. To do this we work closely with other members of Professor Hume’s group, with collaborators in University of Melbourne and Monash University, and with two industrial partners: AstraZeneca, a major global pharmaceutical company and Zimmer, a world leader in orthopaedics. The long-term aim is to generate inhibitors of these genes for therapeutic use. Due to the confidential nature of the CRC interaction with industrial partners, much of this work remains unpublished.

My basic research interests are focused on intracellular signalling and pathological consequences of aberrant signalling molecule function. In particular my laboratory is interested in negative regulators of cell function, as these have received less attention than positive regulators of function. Examples of molecules currently under investigation are: tyrosine phosphatases and their relationships with kinases in cancer and inflammation; the role of the Schlafen family in macrophage function, and a collaborative project with Ass. Profs J. Martin and B. Kobe on endogenous inhibitors of proteases.

Research projects
Identification of genes associated with chronic inflammation
Functional analysis and validation of therapeutic targets for chronic inflammation.
Tyrosine Phosphatases in Macrophage Function

Selected Publications:

Aagaard A, Listwan P, Cowieson N, Huber T, Ravasi T, Wells C, Flanagan JU, Kellie S, Hume DA. (2005). An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: relationship with cysteine protease inhibitors and the tumour suppressor TIG1. Structure 13: 309-317.

Derkinderen P, Scales T, Hanger DP, Leung KY, Ward M, Price C, Bird IN, Perera T, Kellie S, Varndell IA, Sheppard P, Williamson, Reynolds H, Anderton B. (2005). Tyrosine394 is phosphorylated in Alzheimer’s PHF-tau and in fetal tau with c-Abl being the candidate tyrosine kinase. J. Neurosci. 25:6584–6593.

Scaife S, Brown R, Kellie S, Thomas AMC, Salmon M, Buckley CD (2004). Detection of differentially expressed genes in synovial fibroblasts by Restriction Fragment Differential Display. Rheumatology 43: 1346 – 52.

Kellie S, Craggs G, Bird IN, Jones GE (2004). The tyrosine phosphatase DEP-1 induces cytoskeletal rearrangements, aberrant cell-substratum interactions and a reduction in cell proliferation. J. Cell Sci 117: 609-618.

Craggs G & Kellie S (2001). A functional nuclear localisation sequence in the C-terminal domain of SHP-1. J Biol. Chem 276: 23719-23725.

Research Collaborators:

KOBE Bostjan - Protein structure and function
HUME David
MARTIN Jenny
BROWN Melissa - Regulation and function of cancer susceptibility genes

Students:

APTE Simon - PhD
LATTIN Jane - PhD
VAN ZUIJLEN Wendy - PhD
PANETTA Adele - PhD
DAVE Richa - PhD
PICKERING Darren - PhD
ALEXA Andrei - MPhil
KULIS Christina - PhD
SHANKS Melissa - PhD