Biography

Dinny Graham completed her PhD in the Department of Medical Oncology, University of Sydney at Westmead Hospital, studying the transcriptional targets of progesterone in breast cancer. She was awarded a NHMRC CJ Martin Fellowship to travel to Denver, Colorado, USA, to complete a postdoctoral fellowship in the laboratory of Professor Kathryn Horwitz, where she investigated the role of nuclear receptor coregulators in endocrine resistance. She has a number of publications arising from her postdoctoral years, including a major study on a new steroid receptor chaperone, which she first cloned. During her time in the United States, Dinny was awarded grants from the Cancer League of Colorado and the Susan G Komen Breast Cancer Foundation, in addition to a Department of Defense Postdoctoral Fellowship Award. 


Dinny returned to Australia to work with Professor Christine Clarke in the Breast Cancer Group at the Westmead Institute for Cancer Research (WICR) in mid-2001, and has effectively initiated productive new areas of research in the laboratory. She leads the molecular genomics program in the group, examining molecular mechanisms of nuclear receptor action. She has been instrumental in developing high throughput genomic analysis methods in the laboratory and plays an active role in the broader genomics community at Westmead. She co-chairs the Westmead Hub Genomics Committee, and was a driver in establishing gene expression profiling and next-generation sequencing capability in the Westmead Institute Genomics Facility. She is a member of the Westmead Institute Faculty and chairs the Westmead Institute Seminars & Training Committee.

 

Keywords

Nuclear receptors, Breast cancer, Endocrinology, Molecular biology, Computational biology

Themes

Cancer

Research Focus

The ovarian hormone progesterone plays a key role in regulating a diverse range of female reproductive functions, which include development of lobular alveolar structures of the breast, decidualisation of the endometrium, maintenance of bone density and regulation of inflammatory and immune functions. Large randomised trials of exposure to progesterone analogues in hormone replacement therapy have established its role in increasing breast cancer risk, yet the mechanisms that confine this adverse influence to the breast, and likely underlie its diverse tissue specificity, are incompletely understood. Progesterone effects are mediated via the nuclear progesterone receptor (PR), which binds to specific sequences in genomic DNA to regulate transcription of target genes. Ligand activation of PR results in nuclear repositioning into transcriptional hotspots, which are dependent on PR interactions with both the nuclear matrix and chromatin for their fidelity. In the disrupted nuclear environment of breast cancer, aberrant PR nuclear localisation is observed, and results in an altered PR-regulated transcriptional program compared to non-malignant breast. The research that Dinny is doing is aimed at understanding how PR genomic interactions are regulated in a cell type specific manner and identifying how this specificity is disrupted in breast cancer to result in inappropriate progesterone effects.

Other Affiliations

Sydney Medical School > Westmead Clinical School > Westmead Clinical School

Education

  • BSc, Hons, Biochemistry & Mathematics, University of Sydney, Sydney
  • PhD, Medicine, University of Sydney, Sydney