and PostDocs

I welcome motivated PhD students and PostDocs with a biological science background who are interested in stem cells and cancer biology. If you intend to apply for a scholarship to join my lab please contact me well in advance.

Skin epidermis is essential for our survival as terrestrial beings. It provides protection from harmful microbes and other assaults from the external environment, and retains body fluids. To withstand normal wear and tear, the epidermis constantly self-renews. This ability resides in tissue-resident stem cells, which self-renew, preserve, and repair their tissue during homeostasis and following injury.

Long term maintenance of the epidermal stem cell state ex vivo

Trauma, disease or ageing induce tissue damage, which requires the activation of regenerative responses to restore organ function. Constant regeneration and repair of human skin epidermis is endowed by long-lived stem cells (SCs), which generate short-lived, transient-amplifying progenitors that undergo terminal differentiation. Autologous cultures of human epidermal cells (keratinocytes) have long been used to prepare grafts to permanently restore massive epidermal defects in patients suffering from severe burn wounds or hereditary skin blistering diseases. Strikingly, the long-term clinical success of human keratinocyte cultures relies on a defined number of SCs, and premature SC depletion and replicative senescence make ex vivo gene therapy particularly cumbersome and sometimes not feasable. How epidermal SCs can be maintained long-term ex vivo therefore remains a fundamental open question.

By performing genome-wide screens we have recently obtained an extensive catalogue of genes involved in the control of epidermal stem cell self-renewal. The functions of many of these genes are not well understood in an epidermal stem cell context, and we are investigating them by utilizing a broad range of techniques encompassing cell and molecular biology, and tissue engineering.

Long-term culture of human keratinocytes is possible by growing cells in the continuous presence of a fibroblast feeder layer and pharmacological inhibitors of Rho-kinase (ROCKi). By using a multi-omics approach, we are trying to understand and dissect the molecular mechanisms that govern conditional immortalisation of keratinocyte cultures upon ROCKi treatment. 

Skin cancer research

Keratinocyte cancers originate from epidermal stem cells. They are the most commonly diagnosed cancers in humans world-wide. There is ample evidence that keratinocyte cancer stem cells hijack the homeostatic controls that operate in normal stem cells, eliminating those that inhibit differentiation and upregulating those that exert a positive effect on proliferation.

The two closely related transcriptional co-regulator proteins YAP and TAZ have emerged as essential epidermal stemness regulators that balance proliferation and terminal differentiation commitment. Importantly, YAP/TAZ are upregulated and often hyper-active in keratinocyte cancers, where the cancer cells exploit YAP/TAZ’s functions to sustain uncontrolled proliferation and to maintain an undifferentiated stem-like cell state.

How YAP/TAZ control gene expression in the nucleus represents a largely unexplored but promising area to design new modalities of therapeutic anti-cancer interventions. Using multi-omics approaches in combination with genetic gain- and loss-of-function studies in 2D and 3D cell culture systems and zebrafish embryo xenograft models, we are exploring the molecular mechanisms by which YAP and TAZ select their downstream transcriptional programmes and transcriptional partners in normal versus neoplastic epidermal cells, and how YAP/TAZ are regulated inside the nucleus.

Current lab members:

Alexander Howard (PhD student)

Jodie Bojko (PhD student)

Dr Ben Flynn (Postdoc)

Sandra Catalan (Research assistant)

Kelli Gallacher (Research assistant)

Biography

Gernot Walko (Magister rer. nat., Doctor rer. nat) received his undergraduate and postgraduate training in microbiology and molecular biology from the University of Vienna, Austria. He did his PhD in molecular cell biology in the lab of Prof Gerhard Wiche, where his research focused on the roles of cytoskeletal linker proteins in the context of human skin blistering diseases. Following initial postdoctoral training in Vienna, Dr Walko moved to London in 2013, supported a prestigious Marie Curie Intra-European Fellowship, to join the world-leading stem cell lab of Prof Fiona Watt at the newly opened Centre for Stem Cells and Regenerative Medicine at King’s College London. There, his research focused on the molecular mechanisms controlling self-renewal of human epidermal stem cells. Since April 2018, Dr Walko is Principal Investigator in the Department of Biology and Biochemistry at the University of Bath, UK, where his research group studies epidermal stem cells in healthy and diseased skin, with a special focus on the Hippo signalling pathway and its role in skin cancer.