WIMM PI
Curriculum Vitae
Personal Data
Name
Nationality
Email
Roger Patient
UK
roger.patient@imm.ox.ac.uk
Present Position
2004-present
Professor of Developmental Genetics (University of Oxford)
2004-present
Group Leader MHU
2011-present
Deputy Director MHU
Previous Positions
1976-1978
Research Fellow, University of Wisconsin, Madison, Wisconsin, USA.
Principal Investigator: Professor R.D. Wells
1978-1981
Research Fellow, Imperial Cancer Research Fund, London.
Principal Investigator: Professor J.G. Williams
1981-1987
Lecturer in Molecular Genetics, King's College London, Department of
Biophysics
1988-1990
Senior Lecturer in Molecular Genetics, King's College London, Department
Biophysics, Cell & Mol Biol
1990-1996
Reader in Molecular Genetics, King's College London, Molecular Biology &
Biophysics
1990-1992
Acting Head Biophysics, King's College London
1992-1996
Head Molecular Biology & Biophysics, King's College London
1996-1999
Professor of Molecular Genetics, King's College London
1996-1999
Director Developmental Biology Research Centre, King's College London
1999-2004
Professor of Genetics, University of Nottingham
Research Achievements
Just over 30 years ago I chose the globin gene locus to study tissue- and developmental
stage-specific gene expression. Understanding the foetal to adult globin gene switch is still
of great clinical interest, in the hope of ameliorating thalassaemia and sickle cell anaemia. I
chose to study this gene switch in an organism that lends itself to developmental studies,
namely Xenopus laevis. I was successful in cloning and characterizing the globin genes in
this organism, showing for the first time that the alpha and beta globin genes are linked. As I
began to study the mechanisms controlling the expression of this gene family, it became
clear to me that part of the explanation was going to be found in cell lineage switching. We
therefore set out to lineage trace the adult and embryonic blood lineages and showed that
they are distinct from the 32-cell stage of development. In other words, their programming
during development is independent. To determine the molecular basis of this programming,
we began to exploit the genetics and imaging advantages of the zebrafish model, to
complement the classical embryological and anatomical advantages of the Xenopus system.
Since then we have made major contributions to identifying the signals involved in this
programming and the transcription factors that interpret these instructions and programme
the gene expression output of the cells. Initially through the GATA transcription factors, we
began to study cardiac development in parallel, and this has culminated in several papers
showing that the cardiac and blood/endothelial lineages in the embryo share common
regulators and that their fate is determined by the level of FGF signaling received. This
signal differentially influences cross-antagonistic transcription factors in the two derivative
populations. These observations may have implications for stem/progenitor cell identities in
and regeneration of the adult heart.
What are the Future Aims of Your Current Group?
The future aims of my group are to continue to explore the programming of haematopoietic
stem cells (HSCs). The most important feature of stem cells is often quoted as being selfrenewal. The key characteristic of this property is the ability to divide without differentiating.
In other words, the control over differentiation is arguably the critical property of these cells.
We aim to understand how differentiation so far and no further is achieved during embryonic
development, while most other cells around are differentiating completely. Our belief is that
an understanding of this property is contained within the genetic regulatory networks that
control the formation and behaviour of these cells. We are therefore carrying out expression
profiling at increasingly higher levels of completeness, determining the regulatory
relationships between the expressed transcription factors and linking all this to the
environmental signals programming the cells. In order to build these networks, we need to
determine the direct targets for each transcription factor and this requires the development of
new technologies for chromatin immuno-precipitation on small numbers of cells present in
embryos. We are building computer programmes for handling all this information and have
started to identify academic partners to help with modeling of these networks to predict their
behaviour. Alongside this work on normal HSCs, we are beginning to study leukaemic fusion
transcription factors, to determine how they impact these networks and initiate leukaemia.
With respect to our cardiac interest, we are beginning to study heart regeneration in
zebrafish. We have established the heart regeneration models in the lab and are carrying out
detailed comparisons of the networks programming regeneration with those used during
normal development.
How do These Aims Contribute to the Understanding and/or Management of Human
Disease
We expect the knowledge of HSC programming during development to identify important
mechanisms associated with the programming of stem cells in general. This in turn should
provide a better understanding of their behaviour and generate insight into how they might be
controlled, both for regenerative strategies and to control their misbehaviour during cancer.
In addition, this knowledge should eventually enable the production of stem cells in the lab
for transplantation. This could in principle provide matched cells starting from patient-derived
induced pluripotent cells, for example, or alternatively by reprogramming of their fibroblasts
directly to HSCs or other stem cells. Understanding how initiating mutations such as the
leukaemic fusions impact the controlling stem cell networks could provide insight into the
leukaemic process. In the longer term, since several of these fusions have ongoing roles in
the leukaemic process, we will carry out small molecule screens for inhibitors using our
model systems, which have the advantage of representing a more realistic in vivo screen
compared to tissue culture for example. Finally, our studies of regeneration of the heart in
zebrafish, and comparisons with the mouse via collaborators, may help us to identify what is
missing in human hearts and in the longer term contribute to strategies for stimulating repair
in the future.
Lay Summary of Research
Cells in the human body differ from each other by virtue of the different subsets of their
genes that are active. The selection of genes for activity is carried out during embryonic
development and depends on signals received from surrounding cells. We have been
identifying the signals received by the cells which go on to form the stem cells that provide
blood for the life time of the organism. Stem cells are important cells in the adult because
they are responsible for replenishing or repairing tissues. Thus, understanding how they are
controlled is very important for human health. It is now becoming clear that cancer is a stem
cell disease, in other words cancer is caused by rogue cells with stem cell characteristics,
and so understanding this control is even more critical. We are studying these cells in fish
and frogs because they develop externally which allows us to observe what is happening.
However, the mechanisms employed are highly conserved with humans and therefore what
we find out has direct relevance to human health. Zebrafish can regenerate their hearts when
damaged, restoring full function. This capacity is not present in humans. We are studying the
process in zebrafish with a view to finding out what could be done to enable humans to repair
their hearts after damage.
All Publications Over the Past 5 Years
Walmsley M.E., Cleaver, D. and Patient, R.K. (2008) FGF controls the timing of Scl, Lmo2
and Runx1 expression during embryonic blood development. Blood 111, 1157-66.
Dee C.T., Hirst C.S., Shih Y.H., Tripathi V.B., Patient R.K. and Scotting P.J. (2008) Sox3
regulates both neural fate and differentiation in the zebrafish ectoderm. Dev. Biol. 320,
289-301.
Afouda B.A., Martin J., Liu F., Ciau-Uitz A., Patient R.K. and Hoppler S. (2008) GATA
transcription factors integrate Wnt signalling during heart development. Development
135, 3185-90.
Liu F., Walmsley M.E., Rodaway A. and Patient R.K. (2008) Fli1 acts at the top of the
transcriptional network driving blood and endothelial development. Curr. Biol. 18, 123440.
Liu F. and Patient R.K. (2008) Genome-wide analysis of the zebrafish ETS family identifies
three genes required for hemangioblast differentiation or angiogenesis. Circ. Res. 103,
1147-54.
Monteiro R., van Dinther M., Bakkers J., Wilkinson R., Patient R.K., ten Dijke P. and
Mummery C. (2008) Two novel type II receptors mediate BMP signalling and are
required to establish left-right asymmetry in zebrafish. Dev. Biol. 315, 55-71.
Peterkin T., Gibson A. and Patient R.K. (2009) Common genetic control of haemangioblast
and cardiac development in zebrafish. Development 136, 1465-74.
Wilkinson R.N., Pouget C., Gering M., Russell A.J., Davies S.G., Kimelman D. and Patient
R.K. (2009) Hedgehog and Bmp polarize hematopoietic stem cell emergence in the
zebrafish dorsal aorta. Dev. Cell 16, 909-16.
Gering M. and Patient R.K. (2010) Notch signaling and haematopoietic stem cell formation
during embryogenesis. J. Cell Physiol. 222, 11-16.
Ciau-Uitz A., Liu F. and Patient R.K. (2010). Genetic control of hematopoietic development
in Xenopus and zebrafish. Int. J. Dev. Biol. 54, 1139-49.
Ciau-Uitz A., Pinheiro P., Gupta R., Enver T. and Patient R.K. (2010) Tel1/ETV6 specifies
blood stem cells through the agency of VEGF signalling. Dev. Cell 18, 569-78.
Miller L.C. Freter, S., Liu, F., aylor, J.S., Patient, R. and Begbie, J. (2010) Separating early
sensory neuron and blood vessel patterning. Dev. Dyn. 239, 3297-3302
El Omari K., Hoosdally, S.J., Tuladhar, K., Karia, D., Vyas, P., Patient, R., Porcher, C. and
Mancini, E. (2010). Structure of the leukemia oncogene LMO2: implications for the
assembly of a hematopioetic transcription factor complex. Blood 117, 2146-56.
Noseda, M., Peterkin, T., Simoes, F.C., Patient, R. and Schneider, M.D. (2011).
Cardiopoietic factors: extracellular signals for cardiac lineage commitment. Circ. Res.
108, 129-152.
Monteiro R., Pouget C. and Patient R.K. (2011) The gata 1/pu.1 lineage fate paradigm
varies between blood populations and is modulated by tif1y. EMBO J 16, 1093-103.
Simoes F.C., Peterkin T. and Patient R.K. (2011) Fgf differentially controls crossantagonism between cardiac and haemangioblast regulators. Development 138, 323545.
Wang L., Zhang P., Wei Y., Gao Y., Patient R.K. and Liu F. (2011) A blood flow-dependent
klf2a-NO signaling cascade is required for stabilization of hematopoietic stem cell
programming in zebrafish embryos. Blood 118, 4102-10.
Bridge G.E.M., Monteiro R.M., Emuss V., Lagos D., Georgopoulou D., Henderson S.R.,
Patient R.K. and Boshoff C. (2012) The microRNA-30 family regulates DLL4 to influence
endothelial cell behavior during angiogenesis. Blood 120, 5063-72.
Luc S, Luis T.C., Boukarabila H, Macaulay I.C., Buza-Vidas N, Bouriez-Jones T, Lutteropp
M, Woll P.S., Loughran S.J., Mead A.J., Hultquist A, Brown J, Mizukami T, Matsuoka S,
Ferry H, Anderson K, Duarte S, Atkinson D, Soneji S, Domanski A, Farley A, Sanjuan-Pla
A, Carella C, Patient R, de Bruijn M, Enver T, Nerlov C, Blackburn C, Godin I and
Jacobsen S.E. (2012) The earliest thymic T cell progenitors sustain B cell and myeloid
lineage potential. Nat. Immunol. 13, 412-9
Blackledge NP, Long HK, Zhou JC, Kriaucionis S, Patient R, Klose RJ. (2012) Bio-CAP: a
versatile and highly sensitive technique to purify and characterise regions of nonmethylated DNA. Nucleic Acids Res. 40, e32
Wilkinson R.N., Koudijs M.J., Patient R.K., Ingham P.W., Schulte-Merker S, van Eeden F.J.
(2012) Hedgehog signalling via a calcitonin receptor-like receptor can induce arterial
differentiation independently of VEGF signalling in zebrafish. Blood 120, 477-88.
van Riel B, Pakozdi T, Brouwer R, Monteiro R, Tuladhar K, Franke V, Bryne J.C., Jorna R,
Rijkers E.J., van Ijcken W, Andrieu-Soler C, Demmers J, Patient R.K, Soler E, Lenhard B
and Grosveld F. (2012) A novel complex, RUNX1-MYEF2, represses hematopoietic
genes in erythroid cells. Mol. Cell. Biol. 32, 3814-3822
El Omari K., Hoosdally S.J., Tuladhar K., Karia D., Hall-Ponselé E., Platonova O., Vyas P.,
Patient R.K., Porcher C. and Mancini, E.J. (2013) Structural basis for LMO2-driven
recruitment of the SCL:E47bHLH heterodimer to hematopoietic-specific transcriptional
targets. Cell Rep. 4, 135-147.
Leung A., Ciau-Uitz A., Pinheiro, P., Monteiro, R., Zuo, J., Vyas P., Patient R.K.* and
Porcher C.* (2013) Uncoupling VEGFA functions in arteriogenesis and haematopoietic
stem cell specification. Dev. Cell 28, 144-58 (*Joint corresponding authors)
Long H.K, Sims D., Heger A., Blackledge N.P., Kutter C, Wright M.L., Grützner F., Odom
D.T., Patient R.K, Ponting C.P. and Klose R.J. (2013) Epigentic conservation at gene
regulatory elements revealed by non-methylated DNA profiling in seven vertebrates. Elife
2: e00348
Ciau-Uitz A., Pinheiro P., Kirmizitas A., Zuo J., and Patient RK. (2013) VEGFA-dependent
and –independent pathways synergise to drive Scl expression and initiate programming
of the blood stem cell lineage in Xenopus. Development 140, 2632-42.
Wang L., Liu T., Xu L., Gao Y., Wei Y., Duan C., Chen G.Q., Lin S., Patient R.K., Zhang B.,
Hong D., Liu F. (2013) Fev regulates hematopietic stem cell development via ERK
signaling. Blood 122, 367-75.
Zhang C., Patient R.K. and Liu F. (2013) Hematopoietic stem cell developmental and
regulatory signaling in zebrafish. Biochim. Biophys. Acta. 1830, 2370-4.
Sacilotto N., Monteiro R., Fritzsche M., Becker PW., Sanchez-Del-Campo L., Liu K., Pinheiro
P., Ratnayaka I., Davies B., Goding C.R., Patient R.K., Bou-Gharios G., and De Val S.
(2013) Analysis of DII4 regulation reveals a combinatorial role for Sox and Notch in
arterial development. Proc. Natl. Acad. Sci. USA. 110, 11893-8.
Ciau-Uitz A., Wang L., Patient R.K. and Liu F.
(2013) ETS transcription factors in
hematopoietic stem cell development. Blood Cells Mol Dis. 51, 248-55
Nimmo R., Ciau-Uitz A., Ruiz-Herguido C., Soneji S., Bigas A., Patient R.K.*, and Enver T.*
(2013) miR-142-3p Controls the Specification of Definitive Hemangioblasts during
Ontogeny. Dev. Cell 26, 237-49. (*Joint senior authors)
Masiero M., Simões F.C., Han H.D., Snell C., Peterkin T., Bridges E., Mangala L.S., Wu
S.Y., Pradeep S., Li D., Han C., Dalton H., Lopez-Berestein G., Tuynman J.B., Mortensen
N., Li J.L., Patient R.K., Sood A.K., Banham A.H., Harris A.L., and Buffa F.M. (2013) A
Core Human Primary Tumor Angiogenesis Signature Identifies the Endothelial Orphan
Receptor ELTD1 as a Key Regulator of Angiogenesis. Cancer Cell 24, 229-41.
Gorsi B., Liu F., Ma X., Chico T.J., Shrinivasan A., Kramer K.L., Bridges E., Monteiro R.,
Harris A.L., Patient R.K. and Stringer SE. (2014) The heparin sulfate editing enzyme
Sulf1 plays a novel role in zebrafish VegfA-mediated arterial venous identity.
Angiogenesis 17, 77-91.
Chatfield J., O’Reilly M-A., Bachvarova R.F., Ferjentsik Z, Redwood C., Walmsley M.,
Patient RK., Loose M., and Johnson A.D. (2014) Stochastic Specification of PGCs from
Mesoderm Precursors in Vertebrate Embryos. Development 141, 2429-40.
Ciau-Uitz A, Monteiro R, Kirmizitas A, Patient R. (2014) Developmental hematopoiesis:
Ontogeny, genetic programming and conservation. Exp Hematol. 2014 Aug;42(8):669683.
Pouget, C., Peterkin, T., Simoes, F.C., Lee, Y., Traver, D. and Patient, R. (2014) FGF
signalling restricts haematopoietic stem cell specification via modulation of the BMP
pathway. Nat Commun. 5 5588
Ten Key Publications Throughout your Career
Patient R.K., Elkington J.A., Kay R.M. and Williams J.G. (1980) Internal Organization of the
Major Adult - and -Globin Genes of X.laevis. Cell, 21, 565-573.
Enver T., Brewer A.C. and Patient R.K. (1985) Simian Virus 40-Mediated Cis Induction of
the Xenopus -Globin DNase I Hypersensitive Site. Nature, 318, 680-683.
Ciau-Uitz A., Walmsley M.E. and Patient R.K. (2000) Distinct Origins of Adult and
Embryonic Blood in Xenopus. Cell, 102, 787-796.
Gering, M. & Patient, R. (2005) Hedgehog signaling is required for adult blood stem cell
formation in zebrafish embryos. Dev Cell, 8, 389-400.
Liu, F., Walmsley, M., Rodaway, A. & Patient, R. (2008) Fli1 acts at the top of the
transcriptional network driving blood and endothelial development. Curr Biol, 18, 12341240.
Wilkinson R.N., Pouget C., Gering M., Russell A.J., Davies S.G., Kimelman D. and Patient
R.K. (2009) Hedgehog and Bmp polarize hematopoietic stem cell emergence in the
zebrafish dorsal aorta. Dev Cell, 16, 909-16.
Ciau-Uitz, A., Pinheiro, P., Gupta, R., Enver, T. & Patient, R. (2010) Tel1/ETV6 specifies
blood stem cells through the agency of VEGF signaling. Dev Cell, 18, 569-578.
Simoes, F.C., Peterkin, T. & Patient, R. (2011) FGF differentially controls cross-antagonism
between cardiac and haemangioblast regulators. Development, 138, 3235-3245.
Leung A., Ciau-Uitz A., Pinheiro, P., Monteiro, R., Zuo, J., Vyas P., Patient R.K.* and
Porcher C.* (2013) Uncoupling VEGFA functions in arteriogenesis and haematopoietic
stem cell specification. Dev. Cell 28, 144-58 (*Joint corresponding authors)
Nimmo R., Ciau-Uitz A., Ruiz-Herguido C., Soneji S., Bigas A., Patient R.K.*, and Enver T.*
(2013) miR-142-3p Controls the Specification of Definitive Hemangioblasts during
Ontogeny. Dev. Cell 26, 237-49. (*Joint senior authors)
Markers of Esteem
2001
Faculty of 1000
2003
MRC Molecular and Cellular Medicine Board (Deputy Chair)
2004
Special Professor, University of Nottingham
2006
MRC Stem Cell User & Clinical Liaison Committee
2007
BHF Chairs & Programme Grants Committee
2008
International Society for Stem Cell Research Plenary Talk
2008
Oxford Stem Cell Institute Steering Committee
2009
MRC/BHF Joint Stem Cell Panel
2010
Elected Member of EMBO
2011
French Stem Cell Programme (Pasteur Institute) SAB
2014
Royal Society/Wolfson Merit Award
Current Grant Support
MRC Unit Award Haematopoietic Stem Cell Ontogeny 2012-2017 £2M
BHF Intermediate Fellowship (To Dr Rui Monteiro) - TGF signalling in angiogenic and
haemogenic endothelium 2014-2018 £400K
BHF Project Grant - Characterising the active subset of cardiomyocytes in regenerating adult
zebrafish hearts 2014-17 £290K
BHF-CRM Project Grant (With Dr Helle Jorgensen, Cambridge) - Pathways activating cardiac
progenitor potential and proliferation during zebrafish heart regeneration 2014-2017 £270K
BHF Programme Grant (To Prof Paul Riley with 1 Postdoc in my lab full time) Epicardial activation and signalling during cardiovascular repair: comparing regenerative and
non-regenerative models 2013–2018 £1.1m
BHF-CRE Pump-Priming Award (To Dr Filipa Simoes) - Regulatory profiling of the innate
immune response during cardiac regeneration 2014-2015 £27K
BBSRC Project Grant (Co-PI with Drs Catherine Porcher and Aldo Ciau-Uitz) - Investigating
Vegfa transcriptional regulation by co-repressors ETV6 and ETO2 in haematopoietic stem cell
development 2014-17 £270K
MRC Studentship – Notch signalling and HSC development 2010-2014 £120K
WIMM Studentship – Expression profiling emerging HSCs in zebrafish 2013-2017 £120K
BHF Studentship (With Prof Paul Riley) - Investigating the epicardium during cardiac
development and regeneration in zebrafish 2014-17 £120K
Wellcome Trust Studentship - Molecular regulation and function of GATA2 in the programming of
haemogenic endothelium 2014-2017 £180K