Gernot Walko

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.

Research Interests

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. Studying the normal process of tissue homeostasis is providing us a foundation to understand how these processes go awry in skin diseases, including chronic wound-healing, hyper-inflammatory disorders and cancers.

Stem cell-niche interactions in the epidermis

The behaviour of stem cells within a tissue is governed by the three-dimensional microenvironment or niche. To make the crucial decision of whether to remain a stem cell or to commit to differentiation and lineage specification, stem cells must integrate the numerous extrinsic signals they receive from the niche with their cell-intrinsic gene regulatory networks.

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.

To understand how individual stem cells integrate the different niche signals and interpret this complexity to control their fate decisions, we are deconstructing the epidermal stem cell niche ex vivo. To this end, we are developing bioengineered screening platforms that will enable us to assess the combined effects of distinct niche signals on self-renewal and differentiation commitment of single epidermal stem cells in a high content screening setup.

A better understanding of epidermal stem cell-niche cross talk will help us to design improved culture protocols for long-term maintenance of the stem cell state ex vivo.

Skin cancer research

Nonmelanoma skin cancers (NMSC) are the most common malignant tumours in humans. There is ample evidence that epidermal cancer 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-activator proteins YAP and TAZ have emerged as essential epidermal stemness regulators that balance proliferation and terminal differentiation commitment. Importantly, YAP/TAZ are upregulated in NMSC, and epidermal carcinoma cells appear to exploit YAP/TAZ’s functions to sustain their 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 we are exploring the molecular mechanisms by which YAP/TAZ select their downstream transcriptional programs and transcriptional partners in normal versus neoplastic epidermal cells.