Clinical Lecturer in Paediatric Oncology
Anna Rose is a Clinical Lecturer in Paediatric Oncology, working within the Weatherall Institute of Molecular Medicine. Her research focuses on the underlying mechanisms in the development of paediatric solid tumours, with particular focus on the role of the ATRX gene and telomere biology.
Telomeres are the protective cap at the end of chromosomes, which naturally shorten with time. When a telomere becomes critically shortened, the cell will undergo programmed cell death - providing the natural defence against cellular aging. Cancers have overcome this cellular clock, though, and have developed mechanisms for elongating and maintaining telomere length. Telomere maintenance is an essential hallmark of cancer, as it allows malignant cells to divide without limit. One major mechanism for telomere maintenance is called Alternative Lengthening of Telomeres (ALT). The ALT pathway is particularly prevalent in aggressive cancers affecting children and young people, such as high-grade brain tumours and bone tumours. Mutations in ATRX are a poor prognostic factor, and new therapies are needed to treat these aggressive and often incurable cancer types.
The central genetic event underpinning ALT pathway activation is loss of the ATRX gene. However, loss of the ATRX gene alone is not sufficient to turn a normal cell into a malignant one -- so, in addition to ATRX loss, ALT pathway activation requires a second factor. My work focuses on the other genetic and cellular events which lead to the activation of the ALT pathway. We have recently published work demonstrating that the second factor is accumulation of DNA-protein complexes (DPCs).
My ongoing work is continuing to explore the role of trapped DPCs in ALT cancers, with particular focus on two questions:
(1) why are there excessive amounts of trapped DPCs in cancer cells?
(2) how can we manipulate these key pathways, in order to develop novel therapeutic approaches for ALT cancers?
Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA.
Rose AM. et al, (2023), Nucleic Acids Res
Ethnicity, child health and paediatric services.
Qureshi Z. et al, (2022), Arch Dis Child
Risk and Lag-time for Development of Lacrimal Gland Carcinoma Expleomorphic Adenoma: Observations and Conjectural Study.
Rose GE. et al, (2022), Ophthalmic Plast Reconstr Surg
A remarkable case of HbH disease illustrates the relative contributions of the α-globin enhancers to gene expression.
Badat M. et al, (2021), Blood, 137, 572 - 575
Recapitulation of erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) identifies defects in differentiation and nucleolar abnormalities.
Scott C. et al, (2020), Haematologica, Online ahead of print