Tom Milne

Contact information

Email	thomas.milne@imm.ox.ac.uk
PA	Emma Butterfield
PA email	emma.butterfield@ndcls.ox.ac.uk

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Milne Group: Epigenetics and Gene Regulation in Leukaemia Research Group

Thomas Milne

PhD

Associate Professor of Haematology

Tom Milne received a PhD in 2005 that was co-supervised by Dr. Hugh Brock (University of British Columbia) and Dr. Jay Hess (University of Pennsylvania, Philadelphia, USA) working on the wild type function of the Mixed Lineage Leukaemia (MLL) gene. Tom went on to do postdoctoral studies at The Rockefeller University (NY, USA) with Dr. C. David Allis where he worked on the epigenetics of MLL leukaemias. He then became a Group Leader in 2010 at the MRC Molecular Haematology Unit (MRC Weatherall Institute of Molecular Medicine, The University of Oxford, Oxford, UK) and became an Associate Professor of Haematology in 2014. The Milne lab's major area of interest is in epigenetics and gene regulation in leukaemia. Patients with mutations in the MLL gene do not respond well to conventional therapies and thus have very poor survival rates. This is likely due to the fact that MLL is a master regulator that modifies the epigenetic information content of a cell. The overall goal of the Milne lab is to use MLL leukaemias as a system to identify and analyze novel epigenetic pathways in leukaemia and to understand how they interact with transcription factor networks. The end goal will be to use this information to identify potentially novel druggable targets.

Hepcidin is regulated by promoter-associated histone acetylation and HDAC3.
Pasricha SR. et al, (2017), Nat Commun, 8
Mouse models of MLL leukemia: recapitulating the human disease.
Milne TA., (2017), Blood, 129, 2217 - 2223
MLL-AF4 binds directly to a BCL-2 specific enhancer and modulates H3K27 acetylation.
Godfrey L. et al, (2017), Exp Hematol, 47, 64 - 75
MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia.
Kerry J. et al, (2017), Cell Rep, 18, 482 - 495
Instructive Role of MLL-Fusion Proteins Revealed by a Model of t(4;11) Pro-B Acute Lymphoblastic Leukemia.
Lin S. et al, (2016), Cancer Cell, 30, 737 - 749
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.
Stavropoulou V. et al, (2016), Cancer Cell, 30, 43 - 58
MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199.
Benito JM. et al, (2015), Cell Rep, 13, 2715 - 2727
Dangerous liaisons: cooperation between Pbx3, Meis1 and Hoxa9 in leukemia.
Thorne RM. and Milne TA., (2015), Haematologica, 100, 850 - 853
Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia.
Geng H. et al, (2015), Cancer Cell, 27, 409 - 425
Self-Enforcing Feedback Activation Between BCL6 and Tonic Pre-B Cell Receptor Signaling in Acute Lymphoblastic Leukemia
Geng H. et al, (2014), BLOOD, 124
MLL5 expression as a biomarker for DNA hypermethylation and sensitivity to epigenetic therapy.
Milne TA., (2014), Haematologica, 99, 1405 - 1407
Epigenetic control of gene expression in leukemogenesis: Cooperation between wild type MLL and MLL fusion proteins.
Ballabio E. and Milne TA., (2014), Mol Cell Oncol, 1
Epigenetic Control of MLL Fusion Proteins
Ballabio E. et al, (2013), ANNALS OF HEMATOLOGY, 92, S51 - S53
RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.
Wilkinson AC. et al, (2013), Cell Rep, 3, 116 - 127
Integrative epigenomic analysis identifies biomarkers and therapeutic targets in adult B-acute lymphoblastic leukemia
Geng H. et al, (2012), Cancer Discovery, 2, 1006 - 1024
Integrative epigenomic analysis identifies biomarkers and therapeutic targets in adult B-acute lymphoblastic leukemia.
Geng H. et al, (2012), Cancer Discov, 2, 1004 - 1023
Molecular and Epigenetic Mechanisms of MLL in Human Leukemogenesis.
Ballabio E. and Milne TA., (2012), Cancers (Basel), 4, 904 - 944
Intragenic enhancers act as alternative promoters.
Kowalczyk MS. et al, (2012), Mol Cell, 45, 447 - 458
Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia.
Akalin A. et al, (2012), PLoS Genet, 8
Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes.
Biswas D. et al, (2011), Proc Natl Acad Sci U S A, 108, 15751 - 15756
Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions.
Ruthenburg AJ. et al, (2011), Cell, 145, 692 - 706
Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression.
Wang Z. et al, (2010), Cell, 141, 1183 - 1194
Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis.
Milne TA. et al, (2010), Mol Cell, 38, 853 - 863
Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration.
Ferris AL. et al, (2010), Proc Natl Acad Sci U S A, 107, 3135 - 3140
Multiple Interactions Recruit MLL1 and MLL1 Fusion Proteins to the HOXA9 Locus in Leukemogenesis
Milne TA. et al, (2010), Molecular Cell
Regulation of hippocampal H3 histone methylation by acute and chronic stress.
Hunter RG. et al, (2009), Proc Natl Acad Sci U S A, 106, 20912 - 20917
RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells.
Kim J. et al, (2009), Cell, 137, 459 - 471
Chromatin immunoprecipitation (ChIP) for analysis of histone modifications and chromatin-associated proteins.
Milne TA. et al, (2009), Methods Mol Biol, 538, 409 - 423
Interaction of MLL amino terminal sequences with menin is required for transformation.
Caslini C. et al, (2007), Cancer Res, 67, 7275 - 7283
Regulation of MLL1 H3K4 methyltransferase activity by its core components.
Dou Y. et al, (2006), Nat Struct Mol Biol, 13, 713 - 719
A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling.
Wysocka J. et al, (2006), Nature, 442, 86 - 90
Leukemogenic MLL fusion proteins bind across a broad region of the Hox a9 locus, promoting transcription and multiple histone modifications.
Milne TA. et al, (2005), Cancer Res, 65, 11367 - 11374
MLL associates specifically with a subset of transcriptionally active target genes.
Milne TA. et al, (2005), Proc Natl Acad Sci U S A, 102, 14765 - 14770
Taking LSD 1 to a new high.
Wysocka J. et al, (2005), Cell, 122, 654 - 658
WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development.
Wysocka J. et al, (2005), Cell, 121, 859 - 872
Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.
Dou Y. et al, (2005), Cell, 121, 873 - 885
Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors.
Milne TA. et al, (2005), Proc Natl Acad Sci U S A, 102, 749 - 754
Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus.
Hughes CM. et al, (2004), Mol Cell, 13, 587 - 597
Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization.
Zeisig BB. et al, (2004), Mol Cell Biol, 24, 617 - 628
Dimerization of MLL fusion proteins immortalizes hematopoietic cells.
Martin ME. et al, (2003), Cancer Cell, 4, 197 - 207
MLL targets SET domain methyltransferase activity to Hox gene promoters.
Milne TA. et al, (2002), Mol Cell, 10, 1107 - 1117
Tantalus, a novel ASX-interacting protein with tissue-specific functions.
Dietrich BH. et al, (2001), Dev Biol, 234, 441 - 453
The Additional sex combs gene of Drosophila is required for activation and repression of homeotic loci, and interacts specifically with Polycomb and super sex combs.
Milne TA. et al, (1999), Mol Gen Genet, 261, 753 - 761
The Additional sex combs gene of Drosophila encodes a chromatin protein that binds to shared and unique Polycomb group sites on polytene chromosomes.
Sinclair DA. et al, (1998), Development, 125, 1207 - 1216
Enhancer of Polycomb is a suppressor of position-effect variegation in Drosophila melanogaster.
Sinclair DA. et al, (1998), Genetics, 148, 211 - 220
In situ functional dissection of RNA cis-regulatory elements by multiplex CRISPR-Cas9 genome engineering
Fulga TA. et al, Nature Communications

Selected Publications

Mouse models of MLL leukemia: recapitulating the human disease.
Milne TA., (2017), Blood, 129, 2217 - 2223
MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia.
Kerry J. et al, (2017), Cell Rep, 18, 482 - 495
MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199.
Benito JM. et al, (2015), Cell Rep, 13, 2715 - 2727

Recent Publications

Hepcidin is regulated by promoter-associated histone acetylation and HDAC3.
Pasricha SR. et al, (2017), Nat Commun, 8
Mouse models of MLL leukemia: recapitulating the human disease.
Milne TA., (2017), Blood, 129, 2217 - 2223
MLL-AF4 binds directly to a BCL-2 specific enhancer and modulates H3K27 acetylation.
Godfrey L. et al, (2017), Exp Hematol, 47, 64 - 75
MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia.
Kerry J. et al, (2017), Cell Rep, 18, 482 - 495
Instructive Role of MLL-Fusion Proteins Revealed by a Model of t(4;11) Pro-B Acute Lymphoblastic Leukemia.
Lin S. et al, (2016), Cancer Cell, 30, 737 - 749

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ORCID

0000-0002-0413-4271