Projects per year
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:
- Understand the normal developmental biology of the cells that interconvert.
- Identify transcription factors that could be used to differentiate stem cells for therapeutic transplantation and
- Gain insight into how certain cancers develop.
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.
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
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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Collaborations and top research areas from the last five years
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Munoz-Descalzo, S. & Tosh, D.
13/07/16 → …
Project: Research-related funding
Research Leadership Award - The Cretaceous-Paleogne Mass Extinction- Weverity, Recovery and Biogeography
1/09/17 → 2/09/23
Project: UK charity
Grimaldos Rodriguez, C., Rimmer, E. F., Colleypriest, B., Tosh, D., Slack, J. M. W. & Jungwirth, U., 30 Nov 2023, In: Differentiation. 134, p. 1-10
Research output: Contribution to journal › Article › peer-reviewOpen Access3 Downloads (Pure)
Amaral, R., Duci, D., Cotta, F. C., Bacellar, F. L., Oliveira, S., Verret, F., Asadi, K., Vandamme, L. K. J., Reis, N. M., Bryant, L. D., Tosh, D., Mouget, J. L., Perkins, R. & Rocha, P. R. F., 1 Oct 2023, In: Chemical Engineering Journal. 473, 14 p., 144985.
Research output: Contribution to journal › Review article › peer-reviewOpen Access
A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial CellsJoglekar, M. V., Sahu, S., Wong, W. K. M., Satoor, S. N., Dong, C. X., Farr, R. J., Williams, M. D., Pandya, P., Jhala, G., Yang, S. N. Y., Chew, Y. V., Hetherington, N., Thiruchevlam, D., Mitnala, S., Rao, G. V., Reddy, D. N., Loudovaris, T., Hawthorne, W. J., Elefanty, A. G., Joglekar, V. M., & 6 others, 31 Dec 2022, In: Cellular and Molecular Gastroenterology and Hepatology. 13, 5, p. 1530-1553.e4 23 p.
Research output: Contribution to journal › Article › peer-reviewOpen Access
Electrochemical Impedance Spectroscopy as a Tool for Monitoring Cell Differentiation from Floor Plate Progenitors to Midbrain Neurons in Real TimeElghajiji, A., Wang, X., Weston, S. D., Zeck, G., Hengerer, B., Tosh, D. & Rocha, P. R. F., 16 Jun 2021, In: Advanced Biology. 5, 6, 2100330.
Research output: Contribution to journal › Article › peer-reviewOpen Access3 Citations (SciVal)
Molecular mechanisms of transcription factor mediated cell reprogramming: Conversion of liver to pancreasWild, S. L. & Tosh, D., 30 Apr 2021, In: Biochemical Society Transactions. 49, 2, p. 579-590 12 p.
Research output: Contribution to journal › Review article › peer-reviewOpen Access2 Citations (SciVal)
Dataset for "Next-generation in vitro liver model design: combining a permeable polystyrene membrane with a transdifferentiated cell line"