A/Prof Rhys Allan, Lab Head | WEHI Researcher Profile

Q: Revealing the molecular underpinnings of a healthy immune system

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.

Q: Identifying new targets for the treatment of asthma

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.

Q: Rejuvenating the aged immune system through epigenome modulation.

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.

Q: Searching for epigenetic perturbations that drive autoimmune disease

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.

About

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.

Education

Grants and funding

Publications

Selected publications from A/Prof Rhys Allan

Berent S, Allan RS. An X‐tra role for NFκB in gene regulation?. Immunology and Cell Biology. 2025;103(3):10.1111/imcb.12850

Lou J, Deng Q, Zhang X, Bell CC, Das AB, Bediaga NG, Zlatic CO, Johanson TM, Allan RS, Griffin MDW, Paradkar P, Harvey KF, Dawson MA, Hinde E. Heterochromatin protein 1 alpha (HP1α) undergoes a monomer to dimer transition that opens and compacts live cell genome architecture. Nucleic Acids Research. 2024;52(18):10.1093/nar/gkae720

Keenan CR, Coughlan HD, Iannarella N, del Fierro AT, Keniry A, Johanson TM, Chan F, Garnham AL, Whitehead LW, Blewitt ME, Smyth GK, Allan RS. Suv39h-catalyzed H3K9me3 is critical for euchromatic genome organization and the maintenance of gene transcription. Genome Research. 2024;34(4):10.1101/gr.279119.124

Milevskiy MJG, Coughlan HD, Kane SR, Johanson TM, Kordafshari S, Chan F, Tsai M, Surgenor E, Wilcox S, Allan RS, Chen Y, Lindeman GJ, Smyth GK, Visvader JE. Three-dimensional genome architecture coordinates key regulators of lineage specification in mammary epithelial cells. Cell Genomics. 2023;3(11):10.1016/j.xgen.2023.100424

Chan F, Coughlan HD, Ruhle M, Iannarella N, Alvarado C, Groom JR, Keenan CR, Kueh AJ, Wheatley AK, Smyth GK, Allan RS, Johanson TM. Survey of activation‐induced genome architecture reveals a novel enhancer of Myc. Immunology and Cell Biology. 2023;101(4):10.1111/imcb.12626

Zhang S, Rautela J, Bediaga NG, Kolesnik TB, You Y, Nie J, Dagley LF, Bedo J, Wang H, Sun L, Sutherland R, Surgenor E, Iannarella N, Allan R, Souza-Fonseca-Guimaraes F, Xie Y, Wang Q, Zhang Y, Xu Y, Nutt SL, Lew AM, Huntington ND, Nicholson SE, Chopin M, Zhan Y. CIS controls the functional polarization of GM-CSF-derived macrophages. Cellular & Molecular Immunology. 2023;20(1):10.1038/s41423-022-00957-z

Chan WF, Coughlan HD, Chen Y, Keenan CR, Smyth GK, Perkins AC, Johanson TM, Allan RS. Activation of stably silenced genes by recruitment of a synthetic de-methylating module. Nature Communications. 2022;13(1):10.1038/s41467-022-33181-4

Johanson TM, Allan RS. Parsing the transcription factors governing T cell immunity. Nature Immunology. 2022;23(1):10.1038/s41590-021-01075-0

Johanson TM, Allan RS. In Situ HiC. Methods in Molecular Biology. 2022;2458:10.1007/978-1-0716-2140-0_18

Carrington EM, Louis C, Kratina T, Hancock M, Keenan CR, Iannarella N, Allan RS, Wardak AZ, Czabotar PE, Herold MJ, Schenk RL, White CA, D’Silva D, Yang Y, Wong W, Wong H, Bryant VL, Huntington ND, Rautela J, Sutherland RM, Zhan Y, Hansen J, Nhu D, Lessene G, Wicks IP, Lew AM. BCL-XL antagonism selectively reduces neutrophil life span within inflamed tissues without causing neutropenia. Blood Advances. 2021;5(11):10.1182/bloodadvances.2020004139