Our research aims to understand the complex epigenetic circuitry that underlies immune cell function, which should lead to therapies designed to rewire lymphocytes, as new treatments for infection or allergy.
Epigenetic modifications to chromatin may promote immune cell phenotypic stability by influencing the ability of transcription factors to bind to DNA and affecting whether and to what level specific genes are expressed in a cell. However, we are only at the tip of the iceberg in our understanding of how these processes affect lymphocyte fate.
We use a multi-disciplinary approach that combines gene-deficient models, biochemistry and contemporary molecular techniques to develop a fundamental understanding of the chromatin architecture and epigenetic networks that control important steps of immune cell differentiation during development, allergy and infection.
Australia, University of Melbourne, BSc (Hons)
Australia, University of Melbourne, PhD
2014-17 Future Fellowship, Australian Research Council
2013 Millennium Science Award, Lorne Genome Conference
2008-12 INSERM Exchange Fellowship, National Health and Medical Research Council
2007 Sydney Parker Smith Post-doctoral Research Fellowship, Cancer Council Victoria
2005 PhD Achievement Award, QIAGEN
2020-2025 Asthma Research Grant, Stafford Fox Medical Research Foundation
2019-20, Research Grant, LEW Carty Charitable Fund
2013, Medical Research Grant, Rebecca Cooper Foundation
2013, 2015, 2019, 2021 Project/Ideas Grants, National Health and Medical Research Council
Chan, W.F., Coughlan, H.D., Ruhle, M., Iannarella, N., Alvarado, C., Groom, J.R., Keenan, C.R., Kueh, A.J., Wheatley, A.K., Smyth, G.K., Allan, R.S. & Johanson, T.M. Survey of activation-induced genome architecture reveals a novel enhancer of Myc. Immunology & Cell Biology 2023. PMID: 36710659
Chan, W.F., Coughlan, H.D., Chen, Y., Keenan, C.R., Smyth, G.K., Perkins, A.C., Johanson, T.M. & Allan, R.S. Activation of stably silenced genes by recruitment of a synthetic de-methylating module. Nature Communications 2022. PMID: 36151095
Chan, W.F., Coughlan, H.D., Zhou, J.H.S., Keenan, C.R., Bediaga, N.G., Hodgkin, P.D., Smyth, G.K., Johanson, T.M. & Allan, R.S. Pre-mitotic genome re-organisation bookends the B cell differentiation process. Nature Communications 2021. PMID: 33637722
Chan, W.F., Coughlan, H.D., Iannarella, N., Smyth, G.K., Johanson, T.M., Keenan, C.R. & Allan, R.S. Identification and characterization of the long noncoding RNA Dreg1 as a novel regulator of Gata3. Immunology & Cell Biology 2021. PMID: 32970351
Keenan, C.R., Mlodzianoski, M.J., Coughlan, H.D., Bediaga, N.G., Naselli, G., Lucas, E.C., Wang, Q., de Graaf, C.A., Hilton, D.J., Harrison, L.C., Smyth, G.K., Rogers, K.L., Boudier, T., Allan, R.S. & Johanson, T.M. Chromosomes distribute randomly to, but not within, human neutrophil nuclear lobes. iScience 2021. PMID: 33665577
Keenan, C.R., Iannarella, N., Naselli, G., Bediaga, N.G., Johanson, T.M., Harrison, L.C. & Allan, R.S. Extreme disruption of heterochromatin is required for accelerated hematopoietic aging. Blood 2020. PMID: 32305044
Keenan, C.R. & Allan, R.S. Epigenomic drivers of immune dysfunction in aging. Aging Cell 2019. PMID: 30488545
Keenan CR, Iannarella N, Garnham AL, Brown AC, Kim RY, Horvat JC, Hansbro PM, Nutt SL, Allan RS. Polycomb repressive complex 2 is a critical mediator of allergic inflammation. JCI Insight. 2019. PMID: 31092733
Johanson TM, Chan WF, Keenan CR, Allan RS. Genome organization in immune cells: unique challenges. Nature Reviews Immunology. 2019. PMID: 30926914
Johanson TM, Lun ATL, Coughlan HD, Tan T, Smyth GK, Nutt SL, Allan RS. Transcription-factor-mediated supervision of global genome architecture maintains B cell identity. Nature Immunology. 2018. PMID: 30323344
Johanson, T.M., Coughlan, H.D., Lun, A.T.L., Bediaga, N.G., Naselli, G., Garnham, A.L., Harrison, L.C., Smyth, G.K. & Allan, R.S. Genome-wide analysis reveals no evidence of trans chromosomal regulation of mammalian immune development. PLoS Genetics 2018. PMID: 29883495
A cornerstone of immunity is the ability of lymphocytes to remember previous pathogen exposures and respond more rapidly to protect us, however the molecular regulation of this process is still unclear. We use a 4D multi-omic, genome-wide approach to generate a blueprint of how chromatin architecture and transcription is altered during in memory and recalled lymphocytes enabling us to identify the genomic beacons of healthy immunity.
Asthma is the most common chronic lung disease worldwide affecting over 260 million people and causing greater that 450,000 deaths annually (WHO). Although its incidence is still increasing there remains no effective prevention or cure, only management of symptoms. Our approach is to understand the DNA circuitry of the T cells that cause asthma which has led to the identification of a number of excellent new targets for the prevention of asthma. These targets are in the preclinical testing and drug discovery stages and we are also continuing to investigate the molecular mechanisms governing the development of asthmatic immune responses.
As we age our immune cells become less potent. We are interested in why this is the case and are profiling the epigenomic changes associated with immune aging and also testing the possibility that manipulating the epigenome can rejuvenate aging immune cells.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting more than five million people worldwide, with estimated 400,000 new diagnoses/year. We hypothesise that specific alterations to the epigenome result in aberrant immune responses that drive SLE. Revealing these has the potential to uncover new targets for disease treatment. We are using our expertise in molecular and cellular immunology to interrogate samples from juvenile and adult SLE patients.