Liz Patton Research Group

Targeting developmental cell states in melanoma

Liz Patton portrait — Professor Liz Patton

Research in a Nutshell

Melanocyte Development and Melanoma

Melanoma accounts for 80% of the deaths from skin cancer, and incidence continues to rise rapidly. Aggressive and resistant to chemotherapies, individuals with metastatic melanoma often have a life expectancy of less than one year. Our research is focused on understanding how melanocytes – the pigment cells that become melanoma – develop, divide, migrate and maintain homeostatis within their microenvironment, as well as the genetic and cellular events that cause melancoytes 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.

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.

Our lab uses the zebrafish system to understand the development of melanocytes, with a view to how these processes are altered in melanoma. We use genetics and chemical-biology to discover the fundamental processes that contribute to melanocyte development during embryogenesis, and explore how these processes contribute to melanoma development. We have two zebrafish facilities at the IGMM, and access to a wide range of transgenic and genetic lines, diverse chemical libraries, and state-of-the-art imaging facilities.

People
Professor E. Elizabeth Patton	Group Leader
Kelly Blacklock	Veterinary Clinical Research Fellow
Alessandro Brombin	Research Fellow
Hannah Brunsdon	Research Fellow
Jana Travnickova	Research Fellow
Adelaide Young	Research Fellow
Yuting Lu	Research Fellow
Sarah Muise	PhD student
Stephanie MacMaster	PhD student
Oscar Jackson	PhD student (joint PhD student with Martin Taylor)

Contact

E.Patton@ed.ac.uk

Publications

Yuting Lu, Jana Travnickova, Mihaly Badonyi, Florian Rambow, Andrea Coates, Zaid Khan, Jair Marques, Laura Murphy, Pablo Garcia-Martinez, Richard Marais, Pakavarin Louphrasitthiphol, Alex Von Kriegsheim, Joseph A Marsh, Valeria Pavet, Owen J Sansom, Robert Illingworth. ALDH1A3-acetaldehyde re-wires neural crest stem cell and high metabolism states to potentiate melanoma heterogeneity. bioRxiv https://doi.org/10.1101/2023.10.28.564337
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, LuY, 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.