Liz Patton Research Group
Targeting developmental cell states in melanoma
Section: Disease Models
Research in a Nutshell
Melanoma (cancer of the melanocyte) kills over 20,000 Europeans each year and incidence continues to rise rapidly. While melanoma mostly affects older people, in fact, melanoma is one of the rapidly rising cancers in young adults, especially young women. BRAFV600E inhibitors and immune therapy have led to clinically significant improvements in outcomes for melanoma patients, yet many patients with metastatic melanoma rapidly succumb to the disease due to eventual chemoresistance, or insensitivity to the drug. Thus, it is critical to identify new therapies that can act alone or be combined with available treatments for enhanced efficacy and/or to overcome drug resistance.
Our research is focused on understanding how melanocytes – the pigment cells that become melanoma – develop, divide, migrate and maintain homeostasis within their micro-environment, as well as the genetic and cellular events that cause melanocytes to form moles and their progression to invasive cancer. To do this, we use the zebrafish system, which allows both the visualization of developing and migrating melanocytes, as well as their aberrant progression to melanoma. Further, we can use this model system to understand the mechanisms that lead to drug resistance and for pre-clinical drug trials.
The zebrafish is a powerful model system to study developmental biology, chemical biology and disease models. Due to the similar genetic, molecular and cancer pathology between humans and fish, our melanoma progression model can be viewed as an important starting point for identifying novel genes, environmental conditions, and therapeutic compounds that affect melanoma progression.
We use genetics, cellular genomics, live imaging and chemical-biology to discover the fundamental processes that contribute to melanocyte development during embryogenesis, and explore how these processes become dysregulated in melanoma. Our lab at the MRC Human Genetics Unit has close collaborations with the CRUK Scotland Centre, and ultimately, we aim to translate our discoveries in zebrafish to the understanding and treatment of human disease. We have two zebrafish facilities at the IGC led by Dr Cameron Wyatt. We have access to a wide range of transgenic and genetic lines, diverse chemical libraries, and adjacent state-of-the-art imaging, FACS and cellular genomics facilities.
|Professor E. Elizabeth Patton||Group Leader|
|Kelly Blacklock||Veterinary Research Fellow|
|Alessandro Brombin||Research Fellow|
|Hannah Brunsdon||Research Fellow|
|Shiao Chow||Chemistry Research Fellow|
|Jana Travnickova||Research Fellow|
|Adelaide Young||Research Fellow|
|Zhiqiang Zeng||Research Fellow|
|Yuting Lu||PhD student|
|Zahra Massoud||PhD student|
|Sarah Muise||PhD student|
- Travnickova J, Muise S, Wojciechowska S, Brombin A, Zeng Z, Wyatt C, Patton EE. Fate mapping melanoma persister cells through regression and into recurrent disease in adult zebrafish. https://www.biorxiv.org/content/10.1101/2022.03.17.484741v2
- Brunsdon H, Brombin A, Peterson S, Postlethwai JH, Patton EE. Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells. Development 2022 PMID: 35485397
- Brombin A, Simpson DJ, Travnickova J, Brunsdon H, Zeng Z, Lu Y, Young AIJ, Chandra T, Patton EE. Tfap2b specifies an embryonic melanocyte stem cell population that retains adult multi-fate potential. Cell Reports, 2022. PMID: 35021087.
- Johansson JA, Marie KL, Lu Y, Brombin A, Santoriello C, Zeng Z, Zich J, Gautier P, von Kriegsheim A, Brunsdon H, Wheeler AP, Dreger M, Houston DR, Dooley CM, Sims AH, Busch-Nentwich EM, Zon LI, Illingworth RS, Patton EE. PRL3-DDX21 Transcriptional Control of Endolysosomal Genes Restricts Melanocyte Stem Cell Differentiation. Developmental Cell, 2020. PMID:32652076.
- Travnickova J, Wojciechowska S, Khamseh A, Gautier P, Brown DV, Lefevre T, Brombin A, Ewing A, Capper A, Spitzer M, Dilshat R, Semple CA, Mathers ME, Lister JA, Steingrimsson E, Voet T, Ponting CP, Patton EE. Zebrafish MITF-Low Melanoma Subtype Models Reveal Transcriptional Subclusters and MITF-Independent Residual Disease. Cancer Research, 2019. PMID: 31582381.
Full publication list can be found on Research Explorer: Elizabeth Patton — University of Edinburgh Research Explorer
Tamir Chandra (MRC Human Genetics Unit)
Chris Ponting (MRC Human Genetics Unit)
Colin Semple (MRC Human Genetics Unit)
Martin Taylor (MRC Human Genetics Unit)
Robert Semple (The University of Edinburgh)
Veronica Kinsler (Crick Institute)
Richard White (MSKCC, USA)
Partners and Funders
- Medical Research Council
- Melanoma Research Alliance
- Rosetrees Trust
- CLOVES Syndrome Community & Chan Zuckerberg Initiative
- European Research Council
Melanoma, Melanocyte, Zebrafish, Disease models, Chemical genetics
Chemical biology, Drug target ID, CRISPR mutations