Professor David Kent

Research

One of the simplest and most provocative concepts in all of stem cell biology is how a single stem cell can give rise to any of the highly specialised cell types of a given tissue while also having the capacity to make a new equally potent stem cell. At a population level, this decision-making process must exist in a tightly regulated balance in order to avoid tissue degeneration (too few stem cells) or progression to cancer (too many stem cells). The Kent lab explores the biology of adult blood stem cells and the process by which single blood stem cells are subverted to drive blood cancers such as leukaemia.

Brief biography 

David earned a BSc in Genetics and English Literature at the University of Western Ontario, Canada and obtained his PhD in Genetics at the University of British Columbia, Canada. His postdoctoral research was at the University of Cambridge where he primarily studied malignant blood stem cell biology and established his research group in 2015. In 2019, the lab relocated to the University of York and the York Biomedical Research Institute. David has a keen interest in improving the way that we communicate science and educate and train scientists, including launching The Black Hole and writing for the Signals blog on regenerative medicine.  Find him on Twitter, LinkedIN, or ORCID.

Research 

The lab’s research is highly interdisciplinary with four major themes:

Understanding the molecular regulators of normal blood stem cells

Here we focus on how cell fate decisions are made on a single cell level in an effort to understand how to expand stem cell populations outside the body (for cell replacement or as a cell source for gene therapy). We use tools such as single cell RNA-sequencing, clonal tracking and single cell transplantation assays to link molecular profile with cellular function.

Key publications:

• Sakurai et al, Nature 2023
• Che et al, EMBO Reports 2022
• Oedekoven et al, Stem Cell Reports 2021
• Nestorowa et al, Blood 2016
• Wilson et al, Cell Stem Cell 2015

Also check out our recent review: Jassinskaja et al, Blood 2023.

Novel methods to track and quantify blood stem cells in people

Somatic mutations occur in normal human cells over the course of life, are inherited stably by their descendants, and can be reliably detected by DNA sequencing.  Since the vast majority have no phenotypic effect, they can also serve as excellent clonal markers to determine relatedness of cell types and to estimate population size. In addition to exploring the route that various cancers take to developing over time (see above), we are also interested in using this technique to track and quantify stem cells in a range of other haematological settings, including tracking stem cells in gene therapy trials for sickle cell disease.

Key publications:

• Machado et al, Nature 2022
• Lee-Six et al, Nature 2018

Also check our review on the technique: Lee-Six et al, Exp. Hematol 2020

Clonal evolution of cancers from single cells

The early stages of cancer evolution from single cells are observable in haematological malignancies such as myeloproliferative neoplasms and bone marrow failure syndromes. Here we utilise mouse models and primary patient samples to study the molecular and cellular function of mutant versus non-mutant cells to understand clonal competition and to identify potential new therapeutic targets. We also study the role of the immune cell microenvironment in disease evolution.

Key publications

• Ortmann et al, New England Journal of Medicine 2015
• Shepherd et al, Blood 2018
• Obro et al, HemaSphere, 2020

Physical and mechanical biology

The newest area of our lab explores the physical biology of stem cells including the development of new tools/approaches for expanding blood stem cells outside the body. We are exploring the physical and quantitative biology of stem cells through mechanical signalling, mathematical modelling, and the construction of 3D microenvironments and microfluidic devices. In particular, we are interested in understanding the mechanical differences between normal and leukaemic cells and how these might be manipulated for therapeutic benefit.

Lab funding

Our work is funded through Bill and Melinda Gates Foundation, Blood Cancer UK, Medical Research Council, Cancer Research UK, and the European Research Council.

Key collaborators

Internal:  Ian Hitchcock, Katherine Bridge, Bill Grey, Adele Fielding, Jillian Barlow, Will Brackenbury, Dawn Coverley, Andrew Holding, James Hewitson, Dimitris Lagos, Dave Boucher, Peter O'Toole, Steve Johnson, Thomas Krauss.

External: Peter Campbell, Satoshi Yamazaki, David Williams, Julie Makani, Yosuke Tanaka, Cristina Lo Celso, Claus Nerlov, Andrew McKenzie, Brian Huntly, Tony Green, Elisa Laurenti, Alan Warren, and Bertie Gottgens.

Current lab members

• Postdoctoral fellows: Juan Rubio-Lara, Alyssa Cull, Rasha Rezk, Maria Jassinskaja, Leah Etheridge and Daniel Bode.
• Graduate students: Fiona Bain, Lily Cabrera-Cosme, Monika Gonka, Razan Alhefzi, Nathan Hall.
• Research Technicians: Grace Boyd, Joanna Milek, Alex Hogg, Ellie Bennett.

Current opportunities

Our lab is always interested in recruiting talented and motivated scientists - please do not hesitate to get in touch at david.kent@york.ac.uk.

Lab PDRA, Technician and PGR Alumni

James Che, Caroline Oedekoven, Miriam Belmonte, Craig McDonald, Daniel Bode, Mairi Shepherd, Nina Øbro, Megan Davies, Anna Clay, Sandra Pietsch.

+GenerationResearch students; our flagship programme for widening access to research (Will Broster, Sophia Saragoudas, Layan Al-Hariri)

Teaching and scholarship

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My teaching is heavily informed by our research efforts in Genetics, Stem Cells, Regenerative Medicine, Gene Therapy, and Cancer. In addition to this, I have a long history of public engagement and outreach including the creation of The Black Hole, a website and blog that provides information on and analysis of issues related to the education and training of scientists. I was also course director for Hematology 101, a series of web-based lectures on the basics of blood stem cells and their clinical applications.

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I lecture on the Haematology & Immunology in Health & Disease (BIO00085H) and the 3rd year Integrated Masters group projects run by Dr. Jillian Barlow. I have given lectures at the University of Cambridge and Imperial College London in the areas of stem cell biology, blood cancers, and regenerative medicine. 

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My tutorials are designed to have a high level of participant interaction and a strong focus on building written and oral communication skills. Small, focused and regular group discussion is an excellent way to encourage new lines of thinking that reach beyond the core curriculum.

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We are always interested in hearing from bright and motivated young scientists and the interdisciplinary nature of many of our projects means that students from many different areas can find something to pursue in our lab. Overall, we focus on blood stem cell biology but our work encompasses cellular and molecular biology, cancer evolution, mouse models, physical and mechanical biology, computational biology and bioinformatics.