Children's Cancer Research Unit

Molecular Oncology

• Research Directions
• Group Leader Profile
• Recent Publications
• Student Opportunities

Research Directions

The Molecular Oncology group investigates the underlying molecular basis of cancer, by studying a number of amplification target genes which A/Prof. Byrne and her colleagues have identified. Gene amplification represents a mechanism which commonly activates oncogenes, and Dr Byrne's work focuses up the amplification targets tumor protein D52 and MAL2. The tumor protein D52 (or simply D52) gene was identified by Dr Byrne when she was a post-doctoral fellow in France. She subsequently identified two other broadly-expressed members of this family, and the four-transmembrane protein MAL2, which is a common binding partner of D52-like proteins. The D52 gene is increasingly recognised to be overexpressed in different human cancer types, at different stages of tumour progression. Furthermore, D52 overexpression in cell lines increases proliferation and anchorage-independent growth, and confers a metastatic phenotype. Recently, A/Prof. Byrne's group found that high D52 expression in breast cancer is associated with poor survival, in agreement with the results of expression microarray analyses which have included the D52 in gene profiles associated with poor prognosis. The Molecular Oncology group is now working towards understanding how D52 overexpression contributes to cellular transformation and tumor progression, in order to target D52 overexpression therapeutically.

Current laboratory interests include:

• Identifying functional differences between individual D52-like proteins
• the significance of interactions between D52-like proteins and MAL2, and other novel partners
• the consequences of D52 over- and underexpression in model systems, and
• the endogenous expression of D52 and MAL2 in childhood and adult cancers.

Group Leader Profile - A/Prof. Jennifer Byrne

Career Chronology

Jennifer Byrne undertook her PhD with Professor Peter Smith in the University of Queensland's Department of Pathology from 1989-1992. She then spent 3 years in Professor Paul Basset's laboratory in Strasbourg, France as a NH&MRC-funded CJ Martin postdoctoral fellow. She returned to Australia in 1996 to the Children's Medical Research Institute, and then moved to the Children's Cancer Research Unit at The Children's Hospital at Westmead in 1998. She was appointed Acting Head of the Children's Cancer Research Unit in 2008.

Research Highlights

Since first identifying the tumor protein D52 gene in 1995 (Cancer Res. 55: 2896-903), A/Prof Byrne's work has presented a sequence of original discoveries, including identifying other D52-like genes in human and mouse and thereby a novel gene family (Genomics 35: 523-32), heteromeric interactions between D52-like proteins (Oncogene 16: 873-82), 14-3-3 proteins (J. Mol. Biol. 332: 675-687) and the novel MAL2 protein as partners for D52-like proteins (Genomics 76: 81-88), cell cycle regulation of D52-like protein expression in breast carcinoma cells (Exp. Cell Res. 310: 152-165), and frequent D52 overexpression in breast (Genes Chrom. Cancer 29: 48-57), prostate (Cancer Res. 64: 3814-3822) and ovarian cancer (Int. J. Cancer 117: 1049-1054), in part through gene amplification. A/Prof Byrne has also authored the first reviews of D52-like protein expression and function (Biochem Biophys Res Comm 325: 1115-1121, and references below). Over the last 10 years, her work has been supported by project grants and fellowships of a total value of $1,360,000, including a Cancer Institute NSW Career Development fellowship.

Administrative Roles

A/Prof Byrne has been a member of the Cancer Biology NHMRC Grant Review Panel in 2006 and 2007, and previously acted as a member of Specialty Committee B (Cell Biology) for the National Ranking of Cancer Research Grants, from 2002-2004. She is now Chair of the CMRI/ Children's Hospital at Westmead Institutional Biosafety Committee. A/Prof Byrne is also convenor of the Sydney Branch and Member of the National Executive of the Women in Science Enquiry Network.

Postgraduate Teaching

Jennifer Byrne is a Conjoint Associate Professor and Deputy Postgraduate Co-ordinator in the Discipline of Paediatrics and Child Health at the University of Sydney. She is also the Faculty of Medicine's conference chair representing for the 2008 From Cell to Society postgraduate student conference. A/Prof Byrne has supervised 4 higher degree students and 5 BSc/ MBBS (Hons) students to completion, and is currently supervising 2 PhD students and 1 BSc (Hons) student. In recognition of her contributions to postgraduate teaching and her own achievements in postgraduate student supervision, she was awarded both the University of Sydney's College of Health Sciences and Faculty of Medicine Awards for Excellence in postgraduate research student supervision for 2005. A/Prof Byrne was previously awarded the University of Sydney Discipline of Paediatrics and Child Health Teaching Award for postgraduate teaching and supervision in 2003.

Recent Publications (2005-2008)

Boutros R and Byrne JA (2005). D53 (TPD52L1) is a cell cycle regulated protein maximally expressed at the G2-M transition in breast cancer cells. Exp. Cell Res. 310: 152-165.

Byrne JA, Balleine RL, Schoenberg Fejzo M, Mercieca J, Chiew Y-E, Livnat Y, St. Heaps L, Peters G, Byth K, Karlan BY, Slamon DJ, Harnett P, and deFazio A (2005). Tumor Protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer. Int. J. Cancer 117: 1049-1054.

Tiacci E, Orvietani P-L, Bigerna B, Pucciarini A, Liso A, Pacini R, Verducci B, Pulford K, Pileri S, Gambacorta M, Carbone A, Benedetti R, Sciurpi MT, Binaglia L, Byrne JA, and Falini B (2005). A new monoclonal antibody (b-28p) identifies the human tumor protein D52 (TPD52) as a novel B-cell/ plasma cell associated molecule with a unique expression pattern. Blood 105: 2812-2820.

Byrne JA (2006). Tumor protein D52l2. AfCS-Nature Molecule Pages, doi:10.1038/mp.a000074.01.

Byrne JA (2006). Tumor protein D52l1. AfCS-Nature Molecule Pages, doi:10.1038/mp.a000073.01.

Byrne JA (2006). Tumor protein D52. AfCS-Nature Molecule Pages, doi:10.1038/mp.a000072.01. Journal not indexed by ISI.

Barbaric D, Byth K, Dalla-Pozza L and Byrne JA (2006). Expression of tumor protein D52-like genes in childhood leukemia at diagnosis: clinical and sample considerations. Leukemia Res. 30: 1355-1363.

Lewis JD, Payton LA, Whitford JG, Byrne JA, Smith DI, Yang LB, and Bright RK (2007). Induction of tumorigenesis and metastasis by the murine orthologue of Tumor protein D52 (TPD52). Mol. Cancer Res. 5: 133-144.

Payton LA, Lewis JD, Byrne JA, and Bright RK (2007). Vaccination with metastasis-related tumor associated antigen TPD52 and CpG/ODN induces protective tumor immunity. Cancer Immunol. Immunother. 57:799-811.

Shehata M, Bieche I, Boutros R, Weidenhofer J, Fanayan S, Spalding L, Zeps N, Byth K, Bright RK, Lidereau R, and Byrne JA (2008). Non-redundant functions for tumor protein D52-like proteins support specific targeting of TPD52. Clin. Cancer Res. 14: 5050-5060.

Shehata M, Weidenhofer J, Thamotharampillai K, Hardy JR, and Byrne JA (2008). Tumor protein D52 overexpression and gene amplification in cancer- from a mosaic of microarrays. Crit. Rev. Oncogenesis 14: 33-55.

Weidenhofer J and Byrne JA (2009). Isolation of nucleic acids from hard tissues. In: Handbook of Nucleic Acid Purification. Liu D. (Ed.), Taylor & Francis CRC Press, pp. 427-448.

Fanayan S, Shehata M, Agterof AP, McGuckin MA, Alonso MA, and Byrne JA (2009). Mucin 1 (MUC1) is a novel partner for MAL2 in breast carcinoma cells. BMC Cell Biol 10: 7.

Lewis JD, Sullivan LA, Byrne JA, de Riese W, and Bright RK (2009). Memory and cellular immunity induced by a DNA vaccine encoding self antigen TPD52 administered with soluble GM-CSF. Cancer Immunol. Immunother., epub ahead of print.

Alagaratnam S, Hardy JR, Lothe RA, Skotheim RI, and Byrne JA (2008). TPD52, a candidate gene from genomic studies, is overexpressed in testicular germ cell tumours. Mol Cell Endocrinol., epub ahead of print.

   

Student Opportunities

Our group is focussing upon determining the functions of a novel group of genes, the tumor protein D52 family, which we have identified through their expression in human breast cancer. We have found that D52 represents a target for gene amplification in several different forms of cancer, and is therefore likely to play a broad causal role in tumorigenesis and progression. We have also identified a protein partner for D52-like proteins, which is a member of the MAL proteolipid family named MAL2. Current laboratory interests include analysing functional differences between D52-like proteins, the significance of interactions between D52-like proteins and MAL2 and other novel partners, the consequences of D52 over- and under-expression in model systems, and the endogenous expression of D52-like and MAL2 proteins in childhood cancer. Student projects are available in all of these areas.

*Dr Byrne was the recipient of the University of Sydney College of Health Sciences Award for Excellence in Higher Degree Supervision, and the University of Sydney Faculty of Medicine Award for Excellence in Higher Degree Supervision, both in 2005.