Gilan Group - Leukaemia epigenetics

Gilan Lab – Leukaemia epigenetics lab

Gilan lab
2023 Gilan Group - L-R: Dr Omer Gilan, Mr Daniel Neville, Ms Brianna Oakley, Ms Shania Alex, Ms Dhammini Ekanayake Mudiyanselage, Dr Daniel Ferguson

Key terms

  • Haematopoiesis, Acute Myeloid Leukaemia, Mixed Lineage Leukaemia, Chromatin biology, gene regulation

Research overview

The Gilan laboratory at the Australian Centre for Blood Diseases explores how the epigenetic landscape of leukaemia cells is altered and the role it plays in the maintenance of the leukemic state. We aim to understand how the dynamic nature of the epigenome facilitates the response and adaptation (resistance) to targeted therapies. Ultimately the goal is to leverage these insights to identify strategies to reset the cancer cells back to their normal state for therapeutic benefit.

Meet the team

Group Leader

What we are interested in

Fundamental to our understanding of the role of the epigenome in cancer is the intricate world of gene regulation. Gene regulation is an incredibly complex process that underpins the immense diversity of multicellular organisms. Broadly speaking, we aim to make sense of how the many layers of chromatin regulation (epigenome) are linked together to control gene expression. Acute Myeloid Leukaemia (AML) is a devastating disease with a clinically unmet need. It is highly heterogeneous but is caused by relatively few mutations that invariably converge on a block of differentiation and increased self-renewal of blood progenitor cells. Our work spans cellular biology, molecular biology and biochemistry. We utilise a wide variety of cutting edge techniques in the genomics field such as RNA-seq, ChIP-seq, ATAC-seq, CRISPR, CRISPR screens, and mouse models to understand how current and emerging therapies function and to discover new therapeutic targets.

Study with us

See our available research projects or contact Dr Gilan directly at omer.gilan@monash.edu

Projects and Opportunities

  • Determine how the cellular state of leukaemic cells changes in response to epigenetic inhibitors and its implications for treatment strategies
  • Identify novel epigenetic regulators of leukaemia self-renewal
  • Develop a CRISPR-based genetic screen to understand principles of gene regulation

Funding

Our lab is funded by the Victorian Cancer Agency, and the National Health and Medical Research Council.

Publications

Select publications

Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation. Gilan O, Rioja I, Knezevic K, Bell MJ, Yeung MM, Harker NR, Lam EYN, Chung CW, Bamborough P, Petretich M, Urh M, Atkinson SJ, Bassil AK, Roberts EJ, Vassiliadis D, Burr ML, Preston AGS, Wellaway C, Werner T, Gray JR, Michon AM, Gobbetti T, Kumar V, Soden PE, Haynes A, Vappiani J, Tough DF, Taylor S, Dawson SJ, Bantscheff M, Lindon M, Drewes G, Demont EH, Daniels DL, Grandi P, Prinjha RK, Dawson MA. Science. 2020 Apr 24;368(6489):387-394. doi: 10.1126/science.aaz8455. Epub 2020 Mar 19.PMID: 32193360

Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia. Bell CC, Fennell KA, Chan YC, Rambow F, Yeung MM, Vassiliadis D, Lara L, Yeh P, Martelotto LG, Rogiers A, Kremer BE, Barbash O, Mohammad HP, Johanson TM, Burr ML, Dhar A, Karpinich N, Tian L, Tyler DS, MacPherson L, Shi J, Pinnawala N, Yew Fong C, Papenfuss AT, Grimmond SM, Dawson SJ, Allan RS, Kruger RG, Vakoc CR, Goode DL, Naik SH, Gilan O, Lam EYN, Marine JC, Prinjha RK, Dawson MA. Nature Communications. 2019 Jun 20;10(1):2723. doi: 10.1038/s41467-019-10652-9

Id2 and E Proteins Orchestrate the Initiation and Maintenance of MLL-Rearranged Acute Myeloid Leukemia. Ghisi M, Kats L, Masson F, Li J, Kratina T, Vidacs E, Gilan O, Doyle MA, Newbold A, Bolden JE, Fairfax KA, de Graaf CA, Firth M, Zuber J, Dickins RA, Corcoran LM, Dawson MA, Belz GT, Johnstone RW. Cancer Cell. 2016 Jul 11;30(1):59-74. doi: 10.1016/j.ccell.2016.05.019. Epub 2016 Jun 30.PMID: 27374225

Functional interdependence of BRD4 and DOT1L in MLL leukemia.Gilan O, Lam EY, Becher I, Lugo D, Cannizzaro E, Joberty G, Ward A, Wiese M, Fong CY, Ftouni S, Tyler D, Stanley K, MacPherson L, Weng CF, Chan YC, Ghisi M, Smil D, Carpenter C, Brown P, Garton N, Blewitt ME, Bannister AJ, Kouzarides T, Huntly BJ, Johnstone RW, Drewes G, Dawson SJ, Arrowsmith CH, Grandi P, Prinjha RK, Dawson MA. Nature Structural and Molecular Biology. 2016 Jul;23(7):673-81. doi: 10.1038/nsmb.3249.

BET inhibitor resistance emerges from leukaemia stem cells. Fong CY, Gilan O, Lam EY, Rubin AF, Ftouni S, Tyler D, Stanley K, Sinha D, Yeh P, Morison J, Giotopoulos G, Lugo D, Jeffrey P, Lee SC, Carpenter C, Gregory R, Ramsay RG, Lane SW, Abdel-Wahab O, Kouzarides T, Johnstone RW, Dawson SJ, Huntly BJ, Prinjha RK, Papenfuss AT, Dawson MA.Nature. 2015 Sep 24;525(7570):538-42. doi: 10.1038/nature14888. PMID: 26367796

Principles and mechanisms of non-genetic resistance in cancer. Bell CC, Gilan O.Br J Cancer. 2020 Feb;122(4):465-472. doi: 10.1038/s41416-019-0648-6. Epub 2019 Dec 13.PMID: 31831859  Review.

Recent publications