Thomas A. Milne

Zone Equalisation Normalisation For Improved Alignment of Epigenetic Signal

This paper introduces ZEN, a normalization method for genomic data that reduces technical noise while preserving biological signals, improving alignment across different experimental platforms.

The fetal specific gene LIN28B is essential for human fetal B-lymphopoiesis and initiation of KMT2A::AFF1 infant leukemia

This study identifies LIN28B as essential for fetal B-lymphopoiesis and KMT2A::AFF1 infant leukemia initiation, showing its role in promoting proliferation and leukemogenesis.

Menin maintains enhancer-promoter interactions in a leukemia-specific manner

The paper investigates Menin's role in enhancer-promoter interactions in MLL-rearranged and NPM1c leukemia models, finding context-dependent effects on transcriptional regulation and enhancer function.

CD180 identifies chemoresistant stem-like blasts and reveals a KMT2A-driven vulnerability in acute myeloid leukaemia

This paper identifies CD180 as a marker for chemoresistant stem-like blasts in KMT2A-rearranged paediatric AML, showing its absence on normal HSCs and its role as a therapeutic target.

FACT safeguards promoter topology by maintaining nucleosomes and restricting chromatin factor spreading

This study shows FACT maintains promoter topology by preserving nucleosomes and preventing chromatin factor spreading into gene bodies.

TRANCERs: Engineering enhancers into autonomous tissue-specific expression cassettes

TRANCERs convert enhancers into autonomous tissue-specific promoters, enabling precise and programmable gene expression for research and therapy.

Enhancer heterogeneity in acute lymphoblastic leukemia drives differential gene expression between patients

This study identifies enhancer heterogeneity as a driver of transcriptional differences in KMT2A::AFF1 ALL patients, revealing patient-specific enhancer activity at oncogenes.

Inhibition of MLLT1 limits growth of MLL-AF4 leukaemias without killing healthy haematopoietic stem cells

This study shows that inhibiting MLLT1 selectively limits MLL-AF4-driven leukemia growth without harming healthy hematopoietic stem cells.

Sustained MYB activity drives emergent enhancer activation and precise enhancer-promoter interactions

This study shows that MYB activity sustains enhancer-promoter interactions and transcription by maintaining enhancer function in leukemia.

Active regulatory elements recruit cohesin to establish cell-specific chromatin domains.

The paper shows that active enhancers recruit cohesin to form cell-specific chromatin domains, using the alpha globin cluster as a model.

Bi-specific CAR-iNKT cell immunotherapy for high-risk KMT2A-rearranged leukemia outperforms CAR-T in an NKG2D-dependent manner and eradicates leptomeningeal disease

This paper develops bi-specific CAR-iNKT cells targeting CD19 and CD133 for KMT2A-rearranged leukemia, showing superior efficacy over CAR-T in eradicating leptomeningeal disease and inducing remission.

PAF1 and FACT cooperate with MLL-AF4 to drive enhancer activity in leukemia

This study identifies PAF1 and FACT as essential for enhancer activity in MLL-AF4-driven leukemia by maintaining histone acetylation and enhancer-promoter interactions.

Phenotypic analysis of an MLL-AF4 gene regulatory network reveals indirect CASP9 repression as a mode of inducing apoptosis resistance.

The paper constructs a gene regulatory network for MLL-AF4 to reveal an indirect repression of CASP9 via RUNX1 as a mechanism of apoptosis resistance.

BET inhibition disrupts transcription but retains enhancer-promoter contact

The paper shows BET inhibition reduces transcription but not enhancer-promoter contacts, suggesting these processes are separable.

DOT1L inhibition reveals a distinct class ofenhancers dependent on H3K79 methylation

The paper identifies a distinct class of enhancers in leukemia cells that depend on H3K79 methylation and shows that DOT1L inhibition disrupts their function.

Precise tuning of gene expression output levels in mammalian cells

This paper introduces miSFITs, synthetic microRNA response elements that allow precise control of gene expression levels in mammalian cells, showing their utility in modulating antigen expression in a mouse melanoma model.