Patel, de Bruijn and Roy Groups - Impact of endogenous DNA damage and repair in early haematopoiesis
- KJ Patel
ABOUT THE RESEARCH
Haematopoietic stem cells are created during embryo development and they follow a dynamic choreography of anatomical localisation, migrating from the dorsal aorta where they emerge, to the fetal liver and then to the fetal bone marrow. During this developmental window the embryonic/fetal stem cells and progenitors are prone to DNA damage that drives their loss, or may fuel genetic changes such as chromosomal translocations/mutations that can lead to childhood leukaemia and later in adulthood to clonal blood cell production. Our research has shown that aldehydes from maternal alcohol consumption or from metabolism can damage the DNA of the stem cells. The aim of this project is to better understand how maternal metabolism and DNA damage repair and the DNA damage response shape early haematopoietic stem cell instruction, survival and dysfunction.
Additional supervision will be provided by Professor Marella de Bruijn and Professor Anindita Roy (Department of Oncology).
TRAINING OPPORTUNITIES
Students will be enrolled on the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.
Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.
As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.
The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.
REFERENCES
|
1 |
Oberbeck, N, Langevin F, King, G, Wind, N, Crossan G.P and Patel KJ (2014). ‘Maternal aldehyde elimination during pregnancy preserves the fetal genome’. Molecular Cell 55, 807–817. |
|
2 |
Langevin F, Crossan GP, Rosado IV, Arends MJ, Patel KJ (2011) ‘FANCD2 counteracts the toxic effects of naturally produced aldehydes in mice’. Nature 475: 53-58. |
|
3 |
Azzoni, E., Frontera, V., Anselmi, G., ..., Enver, T., de Bruijn, M.F.T.R. 2021. The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition. Cell Reports 37, DOI: 10.1016/j.celrep.2021.110103 |
|
4 |
de Bruijn M and Dzierzak E (2017). Runx transcription factors in the development and function of the definitive hematopoietic system. Blood 129: 2061-2069. |
|
5 |
Muskens IS, Li S, Jackson T, Elliott N, Hansen HM, Myint SS, Pandey P, Schraw J, Roy R, Anguiano J, Goudevenou K, Siegmund KD, Lupo P, de Bruijn M.F.T.R., Walsh KM, Vyas P, Ma X, Roy A, Roberts I, Wiemels JL, de Smith AJ (2021). 'The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis'. Nat Commun, 821. |
|
6 |
Rice S, Jackson T, Crump NT, Fordham N, Elliott N, O'Byrne S, Fanego MdML, Addy D, Crabb T, Dryden C, Inglott S, Ladon D, Wright G, Bartram J, Ancliff P, Mead AJ, Halsey C, Roberts I, Milne TA*, Roy A*.(2021) 'A human fetal liver-derived infant MLL-AF4 Acute Lymphoblastic Leukemia model reveals a distinct fetal gene expression program'. Nat Communications, 12(1) 6905 |
|
7 |
Roy A, Wang G, Iskander D, O’Byrne S, Elliott N, O’Sullivan J, Buck G, Heuston E.F, Wen W.X; Rodriguez Meira A, Hua P, Karadimitiris A, Mead A.J, Bodine D, Roberts I, Psaila B, Thongjuea S (2021). 'Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development'. Cell Reports 36(11): 109698 |
|
8 |
Jardine L, Webb S, et al, Wilson NK, Roy A, Göttgens B, Irene Roberts I, Teichmann S, Haniffa H (2021). Blood and immune development in human fetal bone marrow and Down syndrome. Nature, 598(7880):327-331 |