WIMM PI
Curriculum Vitae
Personal Data
Name
Nationality:
Email
Adam Mead
British
adam.mead@imm.ox.ac.uk
Present Position
2010-present
2011-present
2013-present
2014-present
Honorary Consultant Haematology (OUH)
Clinical lead for the late phase haematology research team (OUH)
Group Leader (WIMM)
MRC Senior Clinical Fellow (WIMM)
Previous positions
1997-1998
1998
1998-2000
2000-2001
2001
2001-2008
2004-2007
2008-2013
House Physician to Professor John Bell–NDM, JR Hospital, Oxford.
House Surgeon Torbay Hospital.
Medical SHO rotation Northwick Park Hospital.
Haematology SHO at University College Hospital.
Intensive care SHO at Charing Cross Hospital.
North Thames Haematology Specialist Registrar Rotation
2001-2002: Whipps Cross Hospital.
2002: St Bartholomew’s Hospital.
2002-2003: Royal London Hospital.
2003-2004: Southend General Hospital
2004-2004: St Bartholomew’s Hospital.
2007-2007: Adolescent Unit, UCH.
2008- 2008: Transplant team UCH.
PhD Thesis: MRC clinical research fellow, Department of Haematology, UCL.
“The clinical and biological consequences of different FLT3 mutations in
patients with acute myeloid leukaemia (AML).” Supervised by Professors
David Linch and Rosemary Gale.
LLR Senior Bennett Fellowship: “The biological impact of different FLT3
mutations and/or mutations of nucleophosmin on murine and human
haematopoiesis”, carried out In the Haematopoietic Stem Cell Biology
laboratory of Professor Sten Eirik Jacobsen at the WIMM.
Research Achievements (2004-2014)
Much of the focus of my research over the past 10 years has been on the characterisation of aberrant
growth factor signalling pathways in malignant haematopoiesis. During my PhD studies at UCL we
demonstrated that distinct classes of activating mutation of FLT3 in patients with acute myeloid leukaemia
were associated with markedly different prognostic impacts, helping to refine stratified medicine
approaches for patients with myeloid leukaemias. During my LLR Senior Bennett Fellowship, we reported a
novel germline activating JAK2-mutation in a family with hereditary thrombocytosis. This was the first
identification of a germline JAK2 mutation, and in addition to providing novel insights into the impact of
JAK2 mutations on haematopoiesis and myeloproliferative disease, it was also instructive for clinical
practice. We also established how FLT3-ITD mutations instruct a myeloid bias in early lympho-myeloid
progenitors, providing the first insights into how a leukaemic mutation targeting a multipotent progenitor
can impact on lineage fate. In addition, we demonstrated the impact of HLA-mismatch on the outcome of
reduced intensity allogeneic transplantation.
During my time in the WIMM I also took the lead in establishing a novel nanofluidic gene expression
platform, allowing analysis of gene expression from low cell numbers, including transcriptomics of single
cells. This has resulted in multiple productive collaborations and, to date, ten high-impact publications.
Whilst establishing my scientific research group in the WIMM, I have also taken the lead in developing the
Haematology Trials Unit. Before my arrival there was no such team; we now have a team of 16 dedicated
research staff with national and international reputation for successfully running trials. I have also
developed an internationally recognised clinical trial portfolio in myeloproliferative neoplasms and am
principal investigator of 12 clinical trials in Oxford and Chief Investigator of 4 UK and international clinical
trials in neoplastic myeloid disorders.
Lay Summary of Research
One of the key challenges in cancer biology is to better understand why patients with the same subtype of
cancer show remarkably different responses to treatment. One emerging explanation for this observation is
that not all cells within a specific cancer behave in the same way. This partly reflects variability in the types
of DNA damage or mutation(s) carried within each cell but might also be related to the type of cell which
carries the mutation(s), as only some cancer cells, known as cancer stem cells, are able to propagate
disease relapse in patients. Our research is focused on the biology of these cancer stem cells.
Our group is applying single cell analysis and state of the art genetic modelling, to better understand the
cancer stem cells which propagate a particular form of blood cancer known as myeloproliferative neoplams
(MPN). Using patient samples, we will analyse cancer stem cells at a single cell level to understand exactly
which cells might be responsible for causing relapse in patients. In order to understand how different types
of cells respond to the acquisition of specific cancer causing mutations, we have also developed a number
of model systems allowing the selective targeting of combinations of different MPN causing mutations to
different types of bone marrow stem cells. It is possible, for example, that the same mutation may behave
very differently depending on the cell type which originally acquires the mutation, thus influencing
influence the resulting disease type, even though the mutation might remain the same.
Through application of these state of the art cell and molecular biology techniques in humans and model
systems, these studies will provide a substantial contribution to the understanding of MPN-cancer stem
cells and the findings will highlight the clinical applicability of single cell technology across cancer biology.
Markers of Esteem
Carl Albert prize, most distinguished graduate St Peter’s College, 1994
Martin Wronker, Oxford University prize for outstanding academic achievement in final honour schools, 1994
Royal Society of Medicine, Pathology Section Prize, 2007
LRF Senior Bennett Fellowship, October 2008 – September 2013
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MRC Senior Clinical Fellowship March 2014
National/International Lectures:
Mechanisms of resistance to JAK2 inhibition, Madrid, 2013
Advances in Haematology, Dublin, 2013
MPN/CML professional meeting, Newcastle, 2013
Molecular Haemopoiesis Day, London, 2012
British Society of Haematology, Glasgow, 2012
MPN Advances Day, London, 2012 and 2013
Imperial College, London, 2011
LLR Grantholders day, London, 2011
Japanese Acute Leukemia Study Group, Tokyo, April 2007
Jikei University Hospital, Tokyo, April 2007
Leicester University Hospital, June 2007
Peer Reviewed Publications over the last 5 years (corresponding author underlined)
2014
Woll, P.S., Kjällquist, U., Chowdhury, O., Doolittle, H., Wedge, D.C., Thongjuea, S., Erlandsson, R., Ngara, M.,
Anderson, K., Deng, Q., Mead, A.J., Stenson, L., Giustacchini, A., Duarte, S., Giannoulatou, E., Taylor, S.,
Karimi, M., Scharenberg, C., Mortera-Blanco, T., Macaulay, I.C., Clark, S., Dybedal, I., Josefsen, D., Fenaux,
P., Hokland, P., Holm, M.S., Cazzola, M., Malcovati, L., Tauro, S., Bowen, D., Boultwood, J., Pellagatti, A.,
Pimanda, J.E., Unnikrishnan, A., Vyas, P., Göhring, G., Schlegelberger, B., Tobiasson, M., Kvalheim, G.,
Constantinescu, S.N., Nerlov, C., Nilsson, L., Campbell, P., Sandberg, R., Papaemmanuil, E., HellströmLindberg, E., Linnarsson, S., Jacobsen, S.E.W. Myelodysplastic syndromes are propagated by rare and
distinct human cancer stem cells in vivo. Cancer Cell, in press.
Grover, A., Mancin, E., Moore, S., Mead, A.J., Atkinson, D., Rasmussen,K.D., O’Carroll, D., Jacobsen, S.E.
and Nerlov, C. Cytokine-mediated guidance of hematopoietic stem cell fate. Journal of Experimental
Medicine, 2014;211:181-188.
2013
Böiers, C., Luc, S., Hultquist, A., Lutteropp, M., Mead, A.J., Kharazi, S., Pontén, A., Jensen, C.T., Sitnicka, E.,
de Bruijn, M. and Jacobsen, S.E. Establishment of lympho-myeloid restricted progenitors prior to the
emergence of definitive hematopoietic stem cells. Cell Stem Cell, 2013;13:535-48.
Sanjuan-Pla, A., Macaulay, I.C., Jensen, C.T., Woll, P.S., Luis, T.C., Mead, A., Moore, S., Carella, C., Bouriez
Jones, T., Chowdhury, O., Stenson, L., Lutteropp, M., Green, J., Fachini, R., Boukarabila, H., Grover, A.,
Gambardella, A., Carrhela, J., Tarrant, P., Atkinson, D., Clark, S., Nerlov, C., and Jacobsen, S.E.W. Plateletbiased stem cells reside at the apex of the hematopoietic stem cell hierarchy. Nature, 2013;502:232-6.
Mead, A.J., Constantinescu, S.N., Jacobsen, S.E. Germline Counterparts of Oncogenic Mutations: Who Gives
a JAK? Invited Editorial Broadcast for Oncotarget,2013;4:814-5.
Harrison, C., Mesa, M., Ross, D., Mead, A., Keohane, C., Gotlib, J. and Verstovsek, S.
Practical management of patients with myelofibrosis receiving ruxolitinib. Expert Review of
Hematology,2013;6:511-23.
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Mead, A.J., Kharazi, S., Macaulay, I., Atkinson, D., Loughran, S., Lutteropp, M., Woll, P., Luc, S., Buza-Vidas,
N., Ferry, H., Nerlov, C., Sitnicka, E., Jacobsen, S.E. FLT3-ITDs introduce a myeloid differentiation and
transformation bias to multipotent lympho-myeloid progenitors. Cell Reports,2013;3:1766-76.
Mead, A.J., Chowdhury, O., Pecquet, C., Dusa, A., Woll, P., Atkinson, D., Burns, A., Score, J., Rugless, M.,
Clifford, R., Moule, S., Bienz, N., Vyas, P., Cross, N., Gale, R.E., Henderson, S., Constantinescu, S.*, Schuh,
A.* and Jacobsen, S.E.W. Hematopoietic impact of isolated germline JAK2-mutation. Blood,2013;121:415665.
2012
Mead, A.J. Ruxolitinib: JAK2 inhibitor for treatment of myelofibrosis. Future Prescriber,2012;13:20-23.
Eyre T, Schwab CJ, Kinstrie R, McGuire AK, Strefford J, Peniket A, Mead A, Littlewood T, Holyoake TL,
Copland M, Moorman AV, Harrison CJ, Vyas P. Episomal amplification of NUP214-ABL1 fusion gene in B-cell
acute lymphoblastic leukemia. Blood,2012;120:4441-3.
Cismasiu*, V., Buza-Vidas*, N., Moore, S., Mead, A.J., Woll, P., Luc, S., Lutteropp, M., Bouriez-Jones, T.,
Atkinson, D., O’Carroll, D., Jacobsen, S.E. and Nerlov, C.. Dicer is essential for maintenance and erythroid
lineage commitment of HSCs. Blood,2012;120:2412-6.
McLornan, D., Mead, A.J. and Harrison, C.N. Allogeneic stem Cell transplant for Myelofibrosis in 2012.
Invited review, British Journal of Haematology,2012;157:413-25.
Roy A, Cowan G, Mead AJ, Filippi S, Bohn G, Chaidos A, Tunstall O, Chan JK, Choolani M, Bennett P, Kumar
S, Atkinson D, Wyatt-Ashmead J, Hu M, Stumpf MP, Goudevenou K, O'Connor D, Chou ST, Weiss MJ,
Karadimitris A, Jacobsen SE, Vyas P, Roberts I. Perturbation of fetal liver hematopoietic stem and
progenitor cell development by trisomy 21. Proc Natl Acad Sci USA, 2012;109:17579-84.
Reilly, J.T., McMullin, M.F., Beer, P.A., Butt, N., Conneally, E., Duncombe, A., Green, A.R., Michaeel, N.G.,
Gilleece, M.H., Hall, G.W., Knapper, S., Mead, A., Mesa, R.A., Sekhar, M., Wilkins B. and Harrison, C.N.
Writing group: British Committee for Standards in Haematology. Guideline for the diagnosis and
management of myelofibrosis. British Journal of Haematology, 2012;158:453-71.
Mead*, A.J., Rugless*, Jacobsen, S.E.W.+, Schuh, A+. Germline activating JAK2-mutation in a family with
hereditary thrombocytosis. New England Journal of Medicine,2012;366:967-9. * or +, equal contribution.
Luc, S., Mizukami, T.*, Boukarabila, H.*, Macaulay, I., Buza-Vidas, N., Bouriez-Jones, T., Lutteropp, M., Woll,
P., Mead, A., Matsuoka, S., Brown, J., Hultquist, A., Ferry, H., Anderson, K., Duarte, S., Atkinson, D., Soneji,
S., Domanski, A., Patient,R., de Bruijn, M., Enver, T., Nerlov, C., Blackburn, C., Godin, I. and Jacobsen, S.E.W.
Lympho-myeloid restricted progenitors seed the embryonic and postnatal thymus. Nature
Immunology,2012;13:412-9.
Reckzeh, K., Bereshchenko, O., Mead, A., Rehn, M., Kharazi, K., Jacobsen, S.E., Nerlov, C.,* and Cammenga,
J.* Molecular and cellular effects of oncogene cooperation in a genetically accurate AML model.
Leukemia,2012;26:1527-36.
2011
Kharazi, S., Mead, A.J., Hultquist, A., Böiers, C., Luc, S., Buza-Vidas, N., Ma, Z., Ferry, H., Atkinson, D.,
Reckzeh, K., Masson, K., Cammenga, J., Rönnstrand, L., Arai, F., Suda, T., Nerlov, C., Sitnicka, E., Jacobsen,
4
S.E. Impact of gene dosage, loss of wild type allele and FLT3 ligand on Flt3-ITD induced myeloproliferation.
Blood, 2011;118:3613-21.
Goardon, N, Marchi, E, Atzberger, A, Quek, L, Schuh, A, Woll, P, Mead, A, Alford, KA, Rout, R, Chaudhury, S,
Gilkes, A, Knapper, S, Soneji, S, Beldjord, K, Begum, S, Rose, S, Geddes, N, Griffiths, M, Standen, G,
Sternberg, A, Cavengh, J, Hunter, H, Bowen, D, Killik, S, Robinson, L, Price, A, Macintyre, E, Burnett, A,
Craddock, C, Enver, T, Jacobsen, SE, Porcher, C, Vyas, P. Comparison of normal human stem/progenitor
populations to those in acute myeloid leukaemia. Cancer Cell, 2011;19:138-52.
2010
Tehranchi*, R., Woll*, P.S., Anderson*, K., Buza-Vidas, N., Mizukami, T., Mead, A.J., Astrand-Grundström, I.,
Strömbeck, B., Horvat, A., Ferry, H., Dhanda, R.S., Hast, R., Rydén, T., Vyas, P., Göhring, G., Schlegelberger,
B., Johansson, B., Hellström-Lindberg, E., List, A., Nilsson, L., Jacobsen, S.E. Persistent malignant stem cells
in del(5q) myelodysplasia in remission. New England Journal of Medicine, 2010; 363: 1025-1037.
Mead, A.J., Thomson, K.J., Morris, E.C., Mohamedbhai, S., Denovan, S., Orti G., Fielding, A.K., Kottaridis,
P.D., Hough, R., Chakraverty, R., Linch, D.C., Mackinnon, S., Peggs, K.S. HLA-mismatched unrelated donors
are a viable alternate graft source for allogeneic transplantation following alemtuzumab-based reduced
intensity conditioning. Blood, 2010;115: 5147-5153.
Ten Key Publications Throughout your Career
Grover, A., Mancin, E., Moore, S., Mead, A.J., Atkinson, D., Rasmussen,K.D., O’Carroll, D., Jacobsen, S.E.
and Nerlov, C. Cytokine-mediated guidance of hematopoietic stem cell fate. Journal of Experimental
Medicine, 2014;211:181-188.
Sanjuan-Pla, A., Macaulay, I.C., Jensen, C.T., Woll, P.S., Luis, T.C., Mead, A., Moore, S., Carella, C., Bouriez
Jones, T., Chowdhury, O., Stenson, L., Lutteropp, M., Green, J., Fachini, R., Boukarabila, H., Grover, A.,
Gambardella, A., Carrhela, J., Tarrant, P., Atkinson, D., Clark, S., Nerlov, C., and Jacobsen, S.E.W. Plateletbiased stem cells reside at the apex of the hematopoietic stem cell hierarchy. Nature, 2013;502:232-6.
Mead, A.J., Kharazi, S., Macaulay, I., Atkinson, D., Loughran, S., Lutteropp, M., Woll, P., Luc, S., Buza-Vidas,
N., Ferry, H., Nerlov, C., Sitnicka, E., Jacobsen, S.E. FLT3-ITDs introduce a myeloid differentiation and
transformation bias to multipotent lympho-myeloid progenitors. Cell Reports,2013;3:1766-76.
Mead, A.J., Chowdhury, O., Pecquet, C., Dusa, A., Woll, P., Atkinson, D., Burns, A., Score, J., Rugless, M.,
Clifford, R., Moule, S., Bienz, N., Vyas, P., Cross, N., Gale, R.E., Henderson, S., Constantinescu, S.*, Schuh,
A.* and Jacobsen, S.E.W. Hematopoietic impact of isolated germline JAK2-mutation. Blood,2013;121:415665.
Roy A, Cowan G, Mead AJ, Filippi S, Bohn G, Chaidos A, Tunstall O, Chan JK, Choolani M, Bennett P, Kumar
S, Atkinson D, Wyatt-Ashmead J, Hu M, Stumpf MP, Goudevenou K, O'Connor D, Chou ST, Weiss MJ,
Karadimitris A, Jacobsen SE, Vyas P, Roberts I. Perturbation of fetal liver hematopoietic stem and
progenitor cell development by trisomy 21. Proc Natl Acad Sci USA, 2012;109:17579-84.
Mead*, A.J., Rugless*, Jacobsen, S.E.W.+, Schuh, A+. Germline activating JAK2-mutation in a family with
hereditary thrombocytosis. New England Journal of Medicine,2012;366:967-9. * or +, equal contribution.
5
Kharazi, S., Mead, A.J., Hultquist, A., Böiers, C., Luc, S., Buza-Vidas, N., Ma, Z., Ferry, H., Atkinson, D.,
Reckzeh, K., Masson, K., Cammenga, J., Rönnstrand, L., Arai, F., Suda, T., Nerlov, C., Sitnicka, E., Jacobsen,
S.E. Impact of gene dosage, loss of wild type allele and FLT3 ligand on Flt3-ITD induced myeloproliferation.
Blood, 2011;118:3613-21.
Mead, A.J., Thomson, K.J., Morris, E.C., Mohamedbhai, S., Denovan, S., Orti G., Fielding, A.K., Kottaridis,
P.D., Hough, R., Chakraverty, R., Linch, D.C., Mackinnon, S., Peggs, K.S. HLA-mismatched unrelated donors
are a viable alternate graft source for allogeneic transplantation following alemtuzumab-based reduced
intensity conditioning. Blood, 2010;115: 5147-5153.
Mead, A.J., Gale, R.E., Hills, R.K., Gupta, M., Young, B.D., Burnett, A.K., Linch, D.C. Conflicting data on the
prognostic significance of FLT3/TKD mutations in acute myeloid leukemia might be related to the incidence
of biallelic disease. Blood,2008; 112: 444-445.
Mead, A., Linch, D., Hills, R., Wheatley, K., Burnett, A. and Gale, R. FLT3 Tyrosine Kinase Domain Mutations
are Biologically Distinct from and have a Significantly More Favorable Prognosis than FLT3 Internal Tandem
Duplications. Blood, 2007; 100: 1262-1270.
Current Grant Support
Kay Kendall Leukaemia Fund £233K
Medical Research Council Senior Clinical Fellowship £1.5M
Gabrielle’s Angel Foundation New Investigator Award £25K
OUH Research Capacity Fund £100K
Leukaemia Research Foundation New Investigator Award $100K
Educational grant from Novartis Pharmaceuticals £296K
Leukaemia and Lymphoma Research (Co-principal investigator) £81K
Leukaemia and Lymphoma Research (co-investigator MAJIC study) £70K
Leukaemia and Lymphoma Research (co-supervisor studentship) £120K
Leukaemia and Lymphoma Research (MPD-RC 114 study) 197K
Clinical trials
Haematology Lead – late phase clinical trials unit, Oxford and Co-principal investigator: LLR Trial
Acceleration Program, Oxford (April 2012-present). From a standing start I have established a team of 16
dedicated research staff with national and international reputation for successfully running trials. I have
also developed an internationally recognised clinical trial portfolio in myeloproliferative neoplasms and I
am principal investigator of 12 clinical trials in Oxford and Chief Investigator of 4 UK and international
multicentre clinical trials in neoplastic myeloid disorders. This clinical practice and many of the trials are
directly relevant for my translational research.
Principal investigator – ENEST1st; A phase IIIb, multicentre, open-label study of nilotinib in adult patients
with newly diagnosed Philadelphia chromosome and/ or bcr-abl positive CML in chronic phase, ENEST1st,
CAMN107EIC01. Closed to recruitment July 2011. Lead UK recruiter.
Principal investigator – RESUME; A phase-3, multi-center, randomized, doubleblind, placebo-controlled,
parallel-group study to compare efficacy and safety of pomalidomide in subjects with myeloproliferative
neoplasm –associated myelofibrosis and red blood cell-transfusiondependence. Closed to recruitment,
April 2012.
6
Principal investigator – JAKARTA; A Phase 3, RandomiSed, Double-Blinded, Placebo Controlled 3 arm Study
of SAR302503 in Patients with Intermediate-2 or High Risk Primary (PMF), Post‑Polycythemia Vera (PPVM),
or Post-Essential Thrombocythemia Myelofibrosis (PTM) with Splenomegaly. Open to recruitment.
Principal Investigator – Clonal Disorders Biobanking study.
Principal Investigator - Myeloproliferative Disorders-Research Consortium (MPD-RC)
MPD-RC 112. Randomized Trial of Pegylated Interferon Alfa-2a versus Hydroxyurea Therapy in the
Treatment of High Risk Polycythemia Vera and High Risk Essential Thrombocythemia
Mandatory Companion Protocol MPD-RC 107. EudraCT #2010-019501-41.
Chief investigator - A UK open-label, multicentre, exploratory Phase II study of INC424 for patients with
primary myelofibrosis (PMF) or post polycythaemia myelofibrosis (PPV MF) or post-essential
thrombocythaemia myelofibrosis (PET-MF). Closed to recruitment.
Co-invesigator – MAJIC; A RandoMised study of best Available therapy versus JAK Inhibition in patients
with high risk Polycythaemia Vera or Essential Thrombocythaemia who are resistant or intolerant to
HydroxyCarbamide. Planned to open Spring 2012. First study to be run through the LLR Trial Acceleration
Program. Open to recruitment.
Chief investigator – PERSIST-1 - A Randomized Controlled Phase 3 Study of Oral Pacritinib versus Best
Available Therapy in Patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or PostEssential Thrombocythemia Myelofibrosis. Open to recruitment.
Principal investigator – EPIC - A Phase 3 Randomized, OpenLabel Study of Ponatinib versus Imatinib in
Adult Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase. Open to recruitment.
Chief Investigator – ENESTfreedom. A single-arm, multicenter, nilotinib treatment-free remission study in
patients with BCR-ABL1 positive Chronic Myelogenous Leukemia in chronic phase who have achieved
durable minimal residual disease (MRD) status on first line nilotinib treatment. Open to recruitment.
Chief Investigator – ENESToberve. An observational, open-label, multi-center, prospective follow-up study
of patients with chronic phase CML treated with Nilotinib in the ENEST1st (CAMN107EIC01) study. Open to
recruitment.
Principal investigator – JakaviPASS. A Non-Interventional Long-term Safety Study of Ruxolitinib in
Myelofibrosis. Open to recruitment.
Co-Chair: Myeloproliferative Disorders-Research Consortium (MPD-RC) MPD-RC Protocol 114. Exploring
the Potential of Dual Kinase JAK 1/2 Inhibitor Ruxolitinib (INC424) with Reduced Intensity Allogeneic
Hematopoietic Cell Transplantation in Patients with Myelofibrosis. Due to open Q2 2014.
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