Dr David Kent
Single cell fate choice in normal and malignant stem cells
Laboratory: Cambridge Stem Cell Institute, Clifford Allbutt Building, Cambridge Biomedical Campus. Departmental Affiliation: Haematology
David Kent earned a B.Sc. in Genetics and English Literature at the University of Western Ontario, Canada (1999-2003) and obtained his Ph.D. in normal adult blood stem cell biology at the University of British Columbia, Canada (2003-2009). His postdoctoral research was at the University of Cambridge where he primarily studied malignant blood stem cell biology. His research group studies fate choice in single blood stem cells and how changes in their regulation lead to cancers.
David is currently the Stem Cell Institute’s Public Engagement Champion and has 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.
- Research: Bloodwise, European Haematology Association, Rosetrees Trust, European Research Council
- Studentships: Welcome Trust, MRC, BBSRC/GSK
- Public Engagement: Royal Society
A small colony of cells derived from a single blood stem cell. Hundreds of such colonies can be assessed for their proliferation kinetics and blood cell types produced
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 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).
Our lab focuses 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) and how subversion of this process leads to cancer.
The lab is currently focused on understanding:
1) The molecular drivers of stem cell heterogeneity (self-renewal durability, lineage commitment)
2) The physical and quantitative biology of stem cells (mechanical signalling, mathematical modelling)
3) How myeloid cancers develop from single stem and progenitor cells in mouse models and primary human patient samples
4) The role of the immune cell microenvironment in disease evolution.
Areas of particular interest include normal stem cell fate choice, clonal evolution of myeloid malignancies, physical biology of stem cells, and tools/approaches for expanding blood stem cells outside the body.
Miriam Belmonte, James Che, Nina Friesgaard Oebro, Caroline Oedekoven, Mairi Shepherd.
Job opportunities in the Kent lab
Motivated students, postdocs and clinicians are always encouraged to contact David directly (email@example.com) to explore potential opportunities to join the lab.
Adult stem cells must balance the types of cells they create in order to provide enough mature cells in the body while also maintaining the stem cell population. These decisions are made on an individual cell-by-cell basis, but as a population, stem cell fate choice must be balanced. Our lab studies how such decisions are made on a single cell level and how poor regulation of these processes leads to cancer.
- Nestorowa S, Hamey FK, Pijuan Sala B, Diamanti E, Shepherd M, Laurenti E, Wilson NK, Kent DG, Göttgens B. A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. Blood. 2016 Aug 25;128(8):e20-31. doi: 10.1182/blood-2016-05-716480. PMID: 27365425
- Schulte R, Wilson NK, Prick JC, Cossetti C, Maj MK, Gottgens B, Kent DG. Index sorting resolves heterogeneous murine hematopoietic stem cell populations. Exp Hematol. 2015 Sep;43(9):803-11. PMCID: PMC4571925
- *Wilson NK, *Kent DG, *Buettner F, Shehata M, Macaulay IC, Calero-Nieto FJ, Sánchez Castillo M, Oedekoven CA, Diamanti E, Schulte R, Ponting CP, Voet T, Caldas C, Stingl J, Green AR, Theis FJ, Göttgens B. *co-first authors. Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations. Cell Stem Cell. 2015 Jun 4;16(6):712-24. PMCID:PMC4460190
- *Ortmann CA, *Kent DG, Nangalia J, Silber Y, Wedge DC, Grinfeld J, Baxter EJ, Massie CE, Papaemmanuil E, Menon S, Godfrey AL, Dimitropoulou D, Guglielmelli P, Bellosillo B, Besses C, Döhner K, Harrison CN, Vassiliou GS, Vannucchi A, Campbell PJ Green AR. *co-first authors. Effect of mutation order on myeloproliferative neoplasms. N Engl J Med. 2015 Feb 12;372(7):601-12. PMCID:PMC4660033
- Kent DG, Li J, Tanna H, Fink J, Kirschner K, Pask DC, Silber Y, Hamilton TL, Sneade R, Simons BD, Green AR. Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion. PLoS Biol. 2013;11(6):e1001576. PMCID:PMC3672217