Perkins Group - Blood Cancer Genomics
Key terms: Inherited anaemias, myelofibrosis and other MPNs, transcription factors, genomics, stem cells, reprograming
To develop a molecular understanding of transcriptional control networks which underpin normal blood stem cell production and blood cancers. To harness this knowledge to cure inherited or acquired human blood diseases.
We are interested in how transcription factors work as master regulators of lineage identity and how mutations in them result in genetic disease and cancer, particularly blood cancer. We employ state-of-the-art genomics techniques such as RNA-seq, ChIP-seq, ATAC-seq, RNA labelling methods, and NGS panel sequencing to interrogate how TFs work and to discover the underlying causes of challenging human cases. We use mouse and zebrafish animal models, including CRISPR/Cas9 gene editing approaches, to ask genetic questions about how blood is made in the embryo. We also have a long-standing interest in the genetics of the myeloproliferative neoplasms (MPNs), particularly the JAK-STAT signaling pathway and how it regulates gene expression. We have been extensively involved in clinical trials of JAK inhibitors in MPNs and are interested in developing new therapies and biomarkers to improve
outcomes for this difficult group of blood cancers.
- Determining how pioneer transcription factors harness epigenetic signals to awaken super enhancers
- Reprograming differentiated adult cells into hematopoietic stem cells
- Gene editing of master regulators of transcription to cure sickle cell disease.
- Analysing new targets of JAK-STAT signalling in normal blood development and blood cancers.
Current Project Funding
Selected Recent Publications
- Kruppeling Erythropoiesis: The increasing importance of DNA sequencing in human genetic disease illustrated by variants of a master regulator of erythropoiesis. Andrew Perkins, Xiangmin Xu, Douglas R. Higgs, The KLF1 Consensus Workgroup, George P. Patrinos, Lionel Arnaud, James J. Bieker and Sjaak Philipsen. Blood (2016) 127(15):1856-62
- Direct targets of the JAK2-STAT5 signalling pathway in erythroid cells. Gillinder K, Tuckey H, Bell C, Huang S, Ilsley M, and Perkins AC. PloS One (accepted June, 2017)
- Krüppel-like factors compete for promoters and enhancers to fine-tune transcription. Ilsley M, Gillinder KH, Huang S, Magor G, Bell C, Crossley MP, Perkins AC. Nucleic Acids Research (Epub: May 24, 2017)
- Pacritinib vs Best Available Therapy for the Treatment of Myelofibrosis Irrespective of Baseline Cytopenias: Results of the International, Randomized, Phase 3 PERSIST-1 Trial. Ruben A. Mesa, Alessandro Vannucchi, Adam Mead, Miklos Egyed, Anita Szoke, Alexandr Suvorov, Janos Jakucs, Andrew Perkins, Ritam Prasad, Jiri Mayer, Judit Demeter, Peter Ganly, Jack Singer, James Bianco, Salim Yazji, Huafeng Zhou, James P. Dean, Peter A te Boekhorst, Jyoti Nangalia, Jean-Jaques Kiladjian, Claire Harrison. Lancet Haematology (2017) May;4(5):e225-e236
- KLF1 null humans display hydrops fetalis and a deranged erythroid transcriptome. Magor G, Tallack M, Gillinder K, Williams B, Perkins AC. Blood (2015) 125(15):2405-17.