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Personal profile

Research interests

My lab is mainly interested in the general phenomenon of cellular reprogramming. Reprogramming is defined as the conversion of one cell type (including stem cells) to another.

We have developed a number of models for the reprogramming of pancreatic cells to liver cells and the reverse, liver to pancreas transformation and for the conversion of oesophagus to intestine (see selected publications).

Studying cellular reprogramming will help us to:

  1. Understand the normal developmental biology of the cells that interconvert.
  2. Identify transcription factors that could be used to differentiate stem cells for therapeutic transplantation and
  3. Gain insight into how certain cancers develop.

Developmental Biology

How does dissecting the cellular and molecular basis of reprogramming help with understanding normal embryonic development? The answer is that the gene (transcription factor) that induces reprogramming is also probably important in distinguishing the two tissues during development. We are currently developing this research to identify developmentally important genes.

Stem Cell Therapy

Stem cells are now entering an exciting phase of research and attention has recently focused on the ability to utilise stem cells as therapeutic modalities. If we can identify key transcription factors (which we call master switch genes) that will induce conversion of one cell type to another, we may be able to use these genes to induce the differentiation of stem cells.

Cancer Research

We now know that in certain pathological conditions reprogramming may predispose to cancer. Perhaps one of the best known examples is Barrett’s metaplasia. In this condition intestinal epithelium appears in the oesophagus. Patients with Barrett’s metaplasia have a greater risk of developing oesophageal adenocarcinoma. In order to gain a better understanding of the disease, we wish to determine the steps leading from normal oesophageal epithelium to intestinal epithelium.

Current lab members:

  • Heather Bone
  • Christopher Brimson (joint with Dr Makoto Furutani-Seiki)
  • Zoe Burke
  • Ed Carter (joint with Professor Steve Ward)
  • James Corbett
  • Yu Chen
  • Leonard Griffiths
  • Barbara Rees
  • Caroline Sangan
  • Michael Storm
  • Nelly Wung 

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Projects

Research Output

Human Breast Cancer Cells Demonstrate Electrical Excitability

Ribeiro, M., Elghajiji, A., Fraser, S. P., Burke, Z., Tosh, D., Djamgoz, M. B. A. & Rocha, P., 30 Apr 2020, In : Frontiers in Neuroscience. 14, 404.

Research output: Contribution to journalArticle

Open Access

Next generation in vitro liver model design: Combining a permeable polystyrene membrane with a transdifferentiated cell line

Luetchford, K. A., Wung, N., Argyle, I. S., Storm, M. P., Weston, S. D., Tosh, D. & Ellis, M. J., 1 Nov 2018, In : Journal of Membrane Science. 565, p. 425-438 14 p.

Research output: Contribution to journalArticle

Open Access
  • 5 Citations (Scopus)

    Spatiotemporal regulation of liver development by the Wnt/β-catenin pathway

    Burke, Z. D., Reed, K. R., Yeh, S-W., Meniel, V., Sansom, O. J., Clarke, A. R. & Tosh, D., 9 Feb 2018, In : Scientific Reports. 8, 1, p. 1-9 9 p., 2735.

    Research output: Contribution to journalArticle

    Open Access
  • Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins

    Gratte, F. D., Pasic, S., Olynyk, J. K., Yeoh, G. C. T., Tosh, D., Coombe, D. R. & Tirnitz-Parker, J. E. E., 12 Mar 2018, In : Scientific Reports. 8, 1, p. 1-13 13 p., 4385.

    Research output: Contribution to journalArticle

    Open Access
  • 3 Citations (Scopus)

    Highly potent and isoform-selective dual-site-binding tankyrase/Wnt signaling inhibitors that increase cellular glucose uptake and have anti-proliferative activity

    Nathubhai, A., Haikarainen, T., Koivunen, J., Murthy, S., Koumanov, F., Lloyd, M., Holman, G., Pihlajaniemi, T., Tosh, D., Lehtio, L. & Threadgill, M., 26 Jan 2017, In : Journal of Medicinal Chemistry. 60, 2, p. 814-820 7 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 22 Citations (Scopus)
    120 Downloads (Pure)

    Thesis

    Differentiation of Pancreatic and Hepatic Cell Types

    Author: Myatt, E., 1 Nov 2013

    Supervisor: Tosh, D. (Supervisor)

    Student thesis: Doctoral ThesisPhD

    File

    Directed Differentiation of Human Embryonic Stem Cells to Mature Hepatocyte-like Cells

    Author: Weston, S., 1 Apr 2020

    Supervisor: Tosh, D. (Supervisor) & Ward, S. (Supervisor)

    Student thesis: Doctoral ThesisPhD

    File

    Hepatocyte-like cells derived from pancreatic cells for use in a bioartifical liver system and in the identification of glucocorticoid receptor interacting partners

    Author: Buchholz, M., 29 Feb 2012

    Supervisor: Tosh, D. (Supervisor), Ellis, M. (Supervisor) & Chaudhuri, J. (Supervisor)

    Student thesis: Doctoral ThesisPhD

    File

    Molecular reprogramming of hepatocytes into beta-like cells

    Author: Thowfeequ, S., 1 Mar 2009

    Supervisor: Slack, J. (Supervisor) & Tosh, D. (Supervisor)

    Student thesis: Doctoral ThesisPhD

    File

    Reprogramming Hepatocytes into Duct-like Cells

    Author: O'Neill, K., 1 Jul 2010

    Supervisor: Slack, J. (Supervisor) & Tosh, D. (Supervisor)

    Student thesis: Doctoral ThesisPhD

    File