Cancer Development and Treatment group

Research overview | The team | Projects | Publications

Research overview

The Cancer Development and Treatment laboratory is located on Level 4 of the Burnet Institute, Alfred Medical Research and Education Precinct (AMREP). Focusing mostly on melanoma, our laboratory works to elucidate mechanisms of cancer initiation and progression, and to develop new therapies. We aim to improve the prevention and treatment of malignant diseases. A broad range of resources are used in our work, including transgenic mice and patient samples collected via the Alfred Cancer Biobank.

Typical methods used in our lab include:

Patient-derived xenograft (PDX)
DNA/RNA sequencing
Flow cytometry
Immunohistochemistry

If you are interested in joining our laboratory as a placement, honours, MD, PhD student, you are welcome to contact the project leads directly or via monc.development@alfred.org.au. We are located on Level 4 of the Paula Fox Melanoma and Cancer Centre (PFMCC).

Meet the team

Group Leader

Principal Investigators

Professional staff
- Dr YouFang Zhang - Senior Research Assistant
- Pacman Szeto – Senior Research Assistant and Laboratory Manager
- Dr Louise Organ - Research Development Manager, Medical Oncology Unit
PhD students
- Dr Christopher Chew
- Zoe Magill (co-supervised by A/Prof Meredith O’Keefe, Monash University)
- Angus Shopee (co-supervised by A/Prof Meredith O’Keefe, Monash University)
- Jack Edwards (co-supervised by A/Prof Sasha Senthi and Prof Menno van Zelm, Monash University)
- Ms Yujia Feng
- Dr Alison Hiong
Academic alumni
- Dr Edith Schneider PhD
- Dr Bill Tang PhD
- Mr Chris Mintoff MPhil
- Dr Samantha Boyle PhD
- Dr Clare Fedele PhD
- Dr William Berry MBBS PhD
- Dr Malaka Ameratunga MBBS FRACP
- Dr Fumihito Noguchi PhD
- Dr Peinan Zhao PhD
- Dr Isobel Leece PhD

Current projects

Project Lead: Prof Mark Shackleton
Melanoma is the most common cancer in young Australians and has one of the highest socioeconomic impacts among all cancers in the country. While treatments for advanced melanoma have improved dramatically, little is known about how this cancer originates from normal melanocytes—the pigment-producing cells in the skin. Our lab is addressing this gap by developing novel assays to isolate and study melanocytes from both mice and humans. These tools have uncovered unexpected diversity among melanocytes, suggesting a hierarchy of progenitor and differentiated cells similar to other organ systems. This research lays the foundation for uncovering how melanocytes grow, renew, differentiate, and potentially become cancerous.
Project lead: Prof Mark Shackleton
Cancer is a heterogeneous disease, with differences not only among different patients, but even amongst the bulk of cells within tumors in individual patients. Intra-tumoral heterogeneity is driven by multiple mechanisms, including dynamic genetic and epigenetic changes acquired by cancer cells during disease progression. These changes allow tumors to evolve and adapt as they grow, spread and undergo treatment. Elucidating causes and consequences of cancer heterogeneity is a high priority, as cancer heterogeneity likely impacts disease outcomes in patients such as the propensities to relapse and metastasize, development of therapy resistance and responsiveness to immunotherapy. This project will examine the origins of intra-patient heterogeneity in cancer, particularly melanoma, and link these to features of disease biology and therapy response, using exceptional resources and world-leading technologies for modeling and molecular profiling of human melanoma (Nature 456:593, Cancer Cell 18:510, Sci Transl Med 4:159ra149, Cancer Res 76:3965). The work will provide fundamental insights into cancer heterogeneity with a view to identifying and exploiting its drivers and effects on tumor biology.
Project Lead: Dr Gamze Kuser-Abali
Nucleotide synthesis enzymes (NSEs) like IMPDH2, GMPS, and CTPS1 are best known for supporting cancer cell growth by producing DNA and RNA building blocks. However, our research has uncovered a surprising new role for these enzymes: when cells are stressed, NSEs can move into the nucleus, bind chromatin, and alter gene expression in ways that suppress tumour progression. We found that the tumour suppressor p53 triggers nuclear import of IMPDH2 by altering its phosphorylation, leading to reduced cancer cell growth and migration. Remarkably, other NSEs show similar features, suggesting a conserved, overlooked tumour-suppressive function. This project aims to unravel the molecular mechanisms behind this nuclear function, assess its relevance across cancer types, and explore its therapeutic potential. By shifting the view of NSEs from purely metabolic players to dual-function enzymes with nuclear anti-cancer activity, we hope to open new strategies for cancer treatment.
Project Lead: Dr Gamze Kuser-Abali
EZH2, a master epigenetic regulator in mammals, is also a driver of cancers in the prostate, breast, brain, ovary and melanoma. Because of this, more than 10 different types of EZH2 inhibitors have been developed by pharmaceutical companies, almost all focusing on its well known methyltransferase activity. Unfortunately, none of these inhibitors has been very successful. Our recent work has shed a light on this perplexing phenomenon. We demonstrated that EZH2 can drive cancer growth via a newly discovered mechanism, which is independent of its methyltransferase activity and dependent on interacting with at least 2 other proteins, IMPDH2 and KLC1. With a long-term goal of translating our preliminary finding into drug discovery efforts, we will be using highly sophisticated biochemical techniques to confirm and understand the exact sites of these protein interactions, which can be targeted in cancer. This project will first confirm EZH2-IMPDH2 interactions and subsequently identify their interaction. Based on these findings, we will develop new ways to inhibit those interactions, and test its effects in cancer growth and metastasis.
Identification of progenitor melanocyte markers in human skin and characterization by engineered mouse models
Project Lead: Dr Adriana Sanna
Melanocytes—the pigment-producing cells in the skin—originate from a rare and poorly understood pool of progenitor cells. These progenitors are essential for maintaining pigmentation and regenerating melanocytes, but their identity and behaviour in human skin remain unclear. This project aims to uncover the molecular markers that define melanocyte progenitors and to understand how these cells function over time. We begin by profiling human skin using high-resolution molecular techniques to identify gene and protein signatures enriched in progenitor-like cells. To test the roles of these candidate markers, we use genetically engineered mouse models that allow us to trace and manipulate specific progenitor populations in vivo. These models help reveal how progenitor-marked cells contribute to melanocyte maintenance, differentiation, and stress responses—shedding light on early events in pigmentation disorders and melanoma development.
Project Lead: Dr Adriana Sanna
Our skin contains special pigment-producing cells called melanocytes, which protect us from the sun’s UV radiation and give skin its color. Sometimes, melanocytes can accumulate mutations and transform into melanoma, one of the most aggressive types of skin cancer.
In our lab, we are creating 3D human skin models, also called skin equivalents, which mimic the structure and function of real skin. These models are made by combining human skin cells in layers to reproduce the epidermis, dermis, and melanocyte niche in the laboratory. By introducing normal melanocytes or melanoma cells into these 3D skin models, we can: -Observe how melanocytes behave in their natural environment; -Investigate how melanoma cells grow, invade, and interact with surrounding skin cells; -Study early steps of melanoma initiation and progression in a controlled system, for example by exposure to UV. This approach allows us to study human skin biology and cancer development without relying solely on animal models, while providing a powerful tool to test hypotheses, visualize cell behavior, and identify potential therapeutic targets.

For further information on all available projects, and to meet our supervisors, please click on the links below.

Mark Shackleton Gamze Kuser Abali Adriana Sanna

Publications

Selected publication

Prospective Isolation According to Melanin Pigment Content of Melanoma Cells With Heterogeneous Potentials for Disease Propagation Clare Fedele, Gamze Kuser-Abali, Ralph Rossi, Peinan Zhao, Jason Li, Malaka Ameratunga, Pacman Szeto, YouFang Zhang, Miles Andrews, Mark Shackleton Pigment Cell Melanoma Res
. 2025 Jul;38(4):e70011. doi: 10.1111/pcmr.70011.

Department of Cancer Medicine

Medicine, Nursing and Health Sciences