Prof Stephen Nutt, Lab Head | WEHI Researcher Profile

Q: Harnessing the power of dendritic cells

Dendritic cells (DCs) are key sentinels that are found throughout the body and act to stimulate protective immune responses against pathogens or cancers. To better tailor the immune response to the challenge at hand, DCs have evolved into multiple anatomically and functionally distinct cell types that form an interface between the external environment and the adaptive immune system. We aim to better understand how this DC diversity is programmed on a transcriptional level as well as to devise approaches to better harness the immune stimulatory properties of DCs to promote key functions such as anti-tumour immunity. Project resource: https://www.wehi.edu.au/news/unravelling-secret-critical-immune-cell-cancer-immunity

Q: The production of antibodies

Antibodies are an essential element of the immune response to infection and underpin the success of current vaccination strategies. Antibodies are produced by plasma cells, the terminally differentiated cells of the B lymphocyte lineage. We are interested in the biological process producing B lymphocytes and plasma cells, as well as the sources of diversity within the immune response. An improved understanding of the production of antibodies will not only provide new approaches to improve vaccination strategies but also provide insights into why this process sometimes goes awry, resulting in autoimmune diseases and the formation of blood cell cancers.

Q: Developing new approaches to treat multiple myeloma

Multiple myeloma is a malignancy of antibody-secreting plasma cells and is one of the most common blood cancers. Despite considerable treatment advances in recent years, many patients relapse, and the disease remains incurable. We aim to use genetic models and human multiple myeloma material to develop new treatment options for multiple myeloma patients.

Q: Elucidating neuroimmune interactions: novel strategies for treatment of chronic diseases

Chronic inflammatory diseases have common pathogenic features of dysregulated immune responses. However, the events leading to this dysregulation are not well understood. The maintenance of mucosal homeostasis requires sensory circuits to continually survey mucosal tracts for perturbations in microbial, dietary, and environmental cues.In this project, we are mapping the interactions between the nervous and immune systems to establish their roles in the maintenance of tissue homeostasis and control of inflammation. An understanding of these pathways will form the basis for exploiting neuronal circuits to promote homeostatic function of immune cells and inform novel therapeutic strategies for inflammatory diseases.Project resources:Gut reaction: how immunity ramps up against incoming threats[https://www.wehi.edu.au/news/gut-reaction-how-immunity-ramps-against-incoming-threats]Gut reaction: eating causes spike in immunity[https://www.wehi.edu.au/news/illuminate-newsletter/march-2020/gut-reaction-eating-causes-spike-immunity]

About

A functional immune system requires the coordinated activity of thousands of individual genes. We study transcription factors, regulatory proteins that act in the cell’s nucleus to control gene expression.

I completed my PhD at the University of Vienna Austria, where I identified a key role played by Pax5 in B cells. Following a post-doc at Cambridge University, I established a research program at WEHI focusing on immune cell differentiation. I am a Professor at the University of Melbourne and a Fellow of the Australian Academy of Science.

Throughout my career I have been intrigued by the regulatory logic used by immune cells in making decisions of cell fate and particularly how transcription factors program the response. We have deciphered how factors such as BLIMP1, PU.1 and IRFs control immune cell differentiation.

We currently focus on the programming of B-cell and plasma cell diversity, as well as efforts to develop new therapies for B-cell diseases including the blood cell cancer multiple myeloma and autoimmune conditions such as Lupus.

I am a founding member of the Snow Centre for Immune Health, a major new initiative that aims to use innovative new research approaches to improve the diagnosis and treatment of people living with diseases of the immune system.

A parallel area of interest are the dendritic cell lineages. We aim to exploit our knowledge in this area to develop a new immunotherapy approach to treat cancer.

Education

Grants and funding

Publications

Selected publications from Prof Stephen Nutt

Broomfield BJ, Tan CW, Qin RZ, Abberger H, Duckworth BC, Alvarado C, Dalit L, Lee CL, Mugan RS, Mazrad ZAI, Muramatsu H, Mackiewicz L, Williams BE, Chen J, Takanashi A, Fabb S, Pellegrini M, Rogers KL, Moon WJ, Pouton CW, Davis MJ, Nutt SL, Pardi N, Wimmer VC, Groom JR. Transient inhibition of type I interferon enhances CD8+ T cell stemness and vaccine protection. Journal of Experimental Medicine. 2025;222(5):10.1084/jem.20241148

Xiong L, Diwakarla S, Chatzis R, Artaiz O, Macowan M, Zhang S, Garnham A, Morgan PK, Mellett NA, Meikle PJ, Lancaster GI, Marsland BJ, Nutt SL, Seillet C. Acute exposure to high-fat diet impairs ILC3 functions and gut homeostasis. Immunity. 2025;:10.1016/j.immuni.2025.03.017

Nie J, Ng AP, Nutt SL. Post-translational control of B lineage commitment. Nature Immunology. 2024;25(12):10.1038/s41590-024-02019-0

Ding Z, Hagan M, Yan F, Schroer NWY, Polmear J, Good-Jacobson KL, Dvorscek AR, Pitt C, O’Donnell K, Nutt SL, Zotos D, McKenzie C, Hill DL, Robinson MJ, Quast I, Koentgen F, Tarlinton DM. Ki67 deficiency impedes chromatin accessibility and BCR gene rearrangement. Journal of Experimental Medicine. 2024;221(8):10.1084/jem.20232160

Saito Y, Harada A, Ushijima M, Tanaka K, Higuchi R, Baba A, Murakami D, Nutt SL, Nakagawa T, Ohkawa Y, Baba Y. Plasma cell differentiation is regulated by the expression of histone variant H3.3. Nature Communications. 2024;15(1):10.1038/s41467-024-49375-x

Jacquelot N, Xiong L, Cao WHJ, Huang Q, Yu H, Sayad A, Anttila CJA, Baldwin TM, Hickey PF, Amann-Zalcenstein D, Ohashi PS, Nutt SL, Belz GT, Seillet C. PD-1 regulates ILC3-driven intestinal immunity and homeostasis. Mucosal Immunology. 2024;17(3):10.1016/j.mucimm.2024.03.002

Audiger C, Laâbi Y, Nie J, Gibson L, Wilson-Annan J, Brook-Carter P, Kueh A, Harris AW, Naik S, Nutt SL, Strasser A, Adams JM, Bouillet P, Chopin M. Mis-expression of GATA6 re-programs cell fate during early hematopoiesis. Cell Reports. 2024;43(5):10.1016/j.celrep.2024.114159

Tellier J, Nutt SL. B cell trajectories influence cancer outcomes. Science. 2024;384(6695):10.1126/science.adp1865

Bergamasco MI, Ranathunga N, Abeysekera W, Li-Wai-Suen CSN, Garnham AL, Willis SN, McRae HM, Yang Y, D’Amico A, Di Rago L, Wilcox S, Nutt SL, Alexander WS, Smyth GK, Voss AK, Thomas T. The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function. Stem Cell Reports. 2024;19(4):10.1016/j.stemcr.2024.02.005

Higuchi R, Tanaka K, Saito Y, Murakami D, Nakagawa T, Nutt SL, Ohkawa Y, Baba Y. Type I interferon promotes the fate of Toll-like receptor 9–stimulated follicular B cells to plasma cell differentiation. PNAS Nexus. 2024;3(4):10.1093/pnasnexus/pgae152