Professor Susan Clark

Professor Susan Clark is a molecular biologist by training. She completed her BSc (Hons1) degree under the supervision of Drs Ken Reed and Lyn Dalgarno at the Australian National University, ACT, Australia, in 1978. She was awarded her PhD (1982) in Biochemistry at University of Adelaide, South Australia, with a thesis entitled "Mapping and Sequencing Human Histone Genes", under the supervision of Dr Julian Wells.

Susan spent her Postdoctoral and Group Leaders years working in the Biotechnology Industry at Biotechnology Australia from 1983-1988 leading studies on the first recombinant porcine diarrhea vaccine development in Australia and eukaryotic expression of recombinant human inhibin, Il-3 and GMCSF.

In 1992, Susan returned to basic research as Group Leader of the Gene Regulation Unit at the Kanematsu Laboratories, Royal Prince Alfred Hospital and CSIRO, North Ryde. During this time she developed and implemented a new technology for DNA methylation analysis- bisulphite sequencing and used this technology to define the nature of aberrant DNA methylation of tumour suppressor genes in cancer.

In 2000, Susan established and headed the Epigenetics Group at the Sydney Cancer Centre, Royal Prince Alfred Hospital. In 2004 she moved her group to the Garvan Institute of Medical Research and initiated and led the growth of the Epigenetics Research Program in the Cancer Research Theme. From 2015- 2109 she served as Inaugural Head, Genomic and Epigenetics Division, followed by Research Director, Genomics & Epigenetics Theme; (2019-2021).

Her DNA methylation studies over the past thirty years have initiated profound questions about the importance of epigenetics in early development and in disease, especially in cancer. Susan has made extensive ground-breaking discoveries relating to DNA methylation patterns in normal and cancer genomes, that have led to the commercialization of new methylation-based tests for early cancer detection. The techniques she pioneered in the early 1990s, including bisulphite sequencing, have revolutionised and now underpin epigen"omic" research. She was founding member of IHEC (International Human Epigenome Consortium) and led the formation and served as president of the AEpiA (Australian Epigenetics Alliance) (2008-2021).

Current Research Plans (2023- 2028):

UNRAVELLING THE IMPACT OF EPIGENOME REMODELLING IN CANCER

SYNOPSIS: Cancer's complexity stems from its genetic and epigenetic aspects. Understanding these mechanisms is vital to advancing cancer treatment.

My research program at the Garvan Institute of Medical Research has previously revealed large scale epigenomic changes commonly occur in cancer cells. However, our knowledge of how alterations to DNA methylation and chromatin remodelling patterns are established remains poor, especially in the context of the three-dimensional (3D) epigenome. Bridging this knowledge gap is pivotal, as it underpins the complexity of gene deregulation and prefaces the mechanisms driving therapy resistance.

VISION: The scope of my 5-year vision revolves around unravelling the intricacies of epigenome biology, DNA methylation dynamics, and 3D chromatin conformation in the context of cancer. This knowledge gain will not only advance cancer management but will also nurture the next generation of research leaders.

AIMS: My lab will focus on two main areas of research addressing:

Aim 1: Molecular mechanisms that drive epigenetic alterations in the 3D cancer genome and microenvironment and development of therapy resistance.

Aim 2: Knowledge translation through development of epigenetic based biomarkers and assessment of new epigenetic combination therapies to treat cancer patients.

Why is it important?:

My research vision is at the heart of Garvans core mission ‘to harness all the information encoded in our genome to better diagnose, treat, predict and prevent disease’ and Garvan Strategy 2030: Discoveries to Impact. Notably, endocrine therapy resistance is a pressing challenge in breast and prostate cancer treatment. My lab’s research tackles this by dissecting resistance mechanisms and proposing innovative strategies to restore sensitivity by directly targeting epigenetic mechanisms of cellular plasticity rather than the end phenotype. Our combined studies will enable epigenetic-based approaches developed in our laboratory, to enter the next phase of clinical translation for improved clinical management of breast and prostate cancer patients.