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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 

Fingerprint Fingerprint is based on mining the text of the person's scientific documents to create an index of weighted terms, which defines the key subjects of each individual researcher.

  • 2 Similar Profiles
Hepatocytes Medicine & Life Sciences
Pancreas Medicine & Life Sciences
Liver Medicine & Life Sciences
Metaplasia Medicine & Life Sciences
Barrett Esophagus Medicine & Life Sciences
Phenotype Medicine & Life Sciences
CCAAT-Enhancer-Binding Protein-beta Medicine & Life Sciences
Dexamethasone Medicine & Life Sciences

Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Projects 2004 2018

Establishment of an animal-free three dimensional model to investigate key signaling pathways

Munoz-Descalzo, S. & Tosh, D.

13/07/16 → …

Project: Research-related fundingPGR Training Grant

University of Bath Industrial Strategy Acceleration Fund (ISAF)

Rocha, P., Moschou, D. & Tosh, D.

2/04/1831/07/18

Project: OtherInternational Collaboration

Advanced Inhibitors of Tankyrases

Tosh, D.

1/10/1530/09/16

Project: UK charity

Advanced Inhibitors of Tankyrases

Tosh, D.

1/10/1430/09/15

Project: UK charity

Advanced Inhibitors of Tankyrases

Tosh, D.

1/10/1331/05/14

Project: UK charity

Research Output 1996 2018

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, 2735

Research output: Contribution to journalArticle

Open Access
beta Catenin
Glutamate-Ammonia Ligase
Liver
Ammonia
Carbamoyl-Phosphate Synthase (Ammonia)

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, 4385

Research output: Contribution to journalArticle

Open Access
Extracellular Matrix Proteins
Hepatocytes
Stem Cells
Serum
Liver
10 Citations

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

Research output: Contribution to journalArticle

Open Access
File
Tankyrases
Inhibitory Concentration 50
Protein Isoforms
Binding Sites
Glucose
4 Citations

Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium

Colleypriest, B. J., Burke, Z. D., Griffiths, L. P., Chen, Y., Yu, W-Y., Jover, R., Bock, M., Biddlestone, L., Quinlan, J. M., Ward, S. G., Mark Farrant, J., Slack, J. M. W. & Tosh, D. 1 Jan 2017 In : Differentiation. 93, p. 39-49 11 p.

Research output: Contribution to journalArticle

Open Access
File
Barrett Esophagus
Metaplasia
Organ Culture Techniques
Epithelium
Phenotype

The Directed Differentiation of Human Embryonic Stem Cells to Lung Cell Lineages

Alaqel, A. 2017 341 p.

Research output: ThesisDoctoral Thesis

Open Access
File
Cell Lineage
Endoderm
Lung
Epithelial Cells
Stem Cells