A/Prof Joanna Groom, Division Head | WEHI Researcher Profile

Q: Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity.

T follicular helper (TFH) cells are a subset of effector CD4+ T cells that promote B cell maturation into high affinity plasma and memory cells. Almost all current vaccines protect via the induction of long-term antibody responses and circulating TFH numbers are reliable biomarkers of vaccination. How diverse pathogen-specific signals direct appropriate protective B cell responses is currently unknown.This project combines diverse infection models, advanced imaging and transcriptional profiling to provide mechanistic insight into the processes underlying TFH heterogeneity, which is likely to be a key source of flexibility for adaptive immunity.Further, a key outcome of this project is to identify mechanisms of TFH heterogeneity in order to treat antibody-dependent inflammatory diseases such as severe asthma, rheumatoid arthritis and lupus.Project resources:Sheikh AA, Groom JR. Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment. Cell Mol Immunol 2021 Mar;18(3):528-538. PMID: 32999454 Kealy L, Di Pietro A, Hailes L, Scheer S, Dalit L, Groom JR, Zaph C, Good-Jacobson KL. The Histone Methyltransferase DOT1L Is Essential for Humoral Immune Responses. Cell Rep 2020 Dec 15;33(11):108504. PMID: 33326791 Sheikh AA, Cooper L, Feng M, Souza-Fonseca-Guimaraes F, Lafouresse F, Duckworth BC, Huntington ND, Moon JJ, Pellegrini M, Nutt SL, Belz GT, Good-Jacobson KL, Groom JR. Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection. Cell Rep. 2019 Aug 13;28(7):1758-1772. PMID: 31412245Piovesan D, Tempany J, Di Pietro A, Baas I, Yiannis C, O'Donnell K, Chen Y, Peperzak V, Belz GT, Mackay CR, Smyth GK, Groom JR, Tarlinton DM, Good-Jacobson KL. c-Myb Regulates the T-Bet-Dependent Differentiation Program in B cells to Coordinate Antibody Responses. Cell Rep. 2017 Apr 18;19(3):461-470. PMID: 28423310

Q: Dissecting the induction and integration of T cell migration cues

Our immune system consists of specialised cells that collaborate to defeat invading pathogens. The integration of migration signals helps balance protective and memory differentiation fates, leading to clearance of infection and cancer and the establishment of immunological memory. How cells navigate these interactions is a dilemma of critical importance to human health globally.This study uses advanced live imaging platforms to determine how T cells integrate complex migration cues. Further, we investigate the cell-type specific patrolling cues that control migration to inflammatory sites to clear infection and cancer.Project resource:Groom JR. Regulators of T-cell fate: Integration of cell migration, differentiation and function. Immunol Rev. 2019 May;289(1):101-114. PMID: 30977199

Q: Targeting T cell interactions to restore balance from inflammation towards immune protection

Following viral infection, immune cells coordinate the induction of inflammatory responses that clear infection and promote protection, while simultaneously balancing the risk of severe immune pathology. The balance between immune protection and pathology has been highlighted in the coronavirus disease 2019 (COVID-19) pandemic.COVID-19 patients can display a spectrum of symptoms that vary from mild, to severe and fatal immune pathology. How this pathophysiology range impacts the formation of protective, humoral immunity has not been tested.Using our 3D imaging platforms we have identified new cellular networks that underpin the decision between inflammation or protection during viral infections. We will examine these T cell interactions in the context of different viral infections, including SARS-CoV-2 to identify therapies that reduce severe immune pathology and improve vaccination success.Project resources:Sheikh AA, Groom JR. Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment. Cell Mol Immunol 2021 Mar;18(3):528-538. PMID: 32999454 Sheikh AA, Cooper L, Feng M, Souza-Fonseca-Guimaraes F, Lafouresse F, Duckworth BC, Huntington ND, Moon JJ, Pellegrini M, Nutt SL, Belz GT, Good-Jacobson KL, Groom JR. Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection. Cell Rep. 2019 Aug 13;28(7):1758-1772. PMID: 31412245.

About

Our lab uses a multi-disciplinary approach to dissect the cellular interactions that underpin immune protection and disease. Our major interests are:
– Identifying factors that promote cell migration, and determining how these factors influence responses to acute and chronic infections, and successful vaccination.
– Determining the spatial niches where cell differentiation decisions occur during immune responses.
– Identifying novel mechanisms that resolve inflammation to limit immune pathology and promote life-long memory (particularly related to COVID-19).
– Transcriptionally dissecting the cellular conversations that mediate flexible immune responses and understanding how these are altered in asthma and lupus.
– Identifying pathways to target these processes as treatments for infectious and inflammatory diseases and to strategise vaccine design.

Systems we use include:
– Advanced imaging methods including whole 3D organ imaging and time-lapse imaging of cell location and migration decisions.
– Diverse infection models (viral, bacterial, helminth and fungal) and healthy and patient tissue samples to study flexible immune responses and animal models of inflammatory diseases.
– Development and analysis of reporter and conditional knockout models to identify how new factors regulate immune protection and memory responses.
– Global gene expression profiling of cells based on cellular interactions and positioning during immune responses.

Education

Grants and funding

Publications

Selected publications from A/Prof Joanna Groom

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

Broomfield BJ, Groom JR. Defining the niche for stem-like CD8+ T cell formation and function. Current Opinion in Immunology. 2024;89:10.1016/j.coi.2024.102454

Cooper L, Xu H, Polmear J, Kealy L, Szeto C, Pang ES, Gupta M, Kirn A, Taylor JJ, Jackson KJL, Broomfield BJ, Nguyen A, Gago da Graça C, La Gruta N, Utzschneider DT, Groom JR, Martelotto L, Parish IA, O’Keeffe M, Scharer CD, Gras S, Good-Jacobson KL. Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection. Immunity. 2024;57(5):10.1016/j.immuni.2024.03.016

Abberger H, Groom JR. Macro-clusters: CD301b+ DCs prime Th2 responses. Journal of Experimental Medicine. 2024;221(4):10.1084/jem.20240088

Torres SV, Man K, Elmzzahi T, Malko D, Chisanga D, Liao Y, Prout M, Abbott CA, Tang A, Wu J, Becker M, Mason T, Haynes V, Tsui C, Shakiba MH, Hamada D, Britt K, Groom JR, McColl SR, Shi W, Watt MJ, Le Gros G, Pal B, Beyer M, Vasanthakumar A, Kallies A. Two regulatory T cell populations in the visceral adipose tissue shape systemic metabolism. Nature Immunology. 2024;25(3):10.1038/s41590-024-01753-9

Tellier J, Tarasova I, Nie J, Smillie CS, Fedele PL, Cao WHJ, Groom JR, Belz GT, Bhattacharya D, Smyth GK, Nutt SL. Unraveling the diversity and functions of tissue-resident plasma cells. Nature Immunology. 2024;25(2):10.1038/s41590-023-01712-w

Zaini A, Dalit L, Sheikh AA, Zhang Y, Thiele D, Runting J, Rodrigues G, Ng J, Bramhall M, Scheer S, Hailes L, Groom JR, Good-Jacobson KL, Zaph C. Heterogeneous Tfh cell populations that develop during enteric helminth infection predict the quality of type 2 protective response. Mucosal Immunology. 2023;16(5):10.1016/j.mucimm.2023.06.007

Wang N, Scott TA, Kupz A, Shreenivas MM, Peres NG, Hocking DM, Yang C, Jebeli L, Beattie L, Groom JR, Pierce TP, Wakim LM, Bedoui S, Strugnell RA. Vaccine-induced inflammation and inflammatory monocytes promote CD4+ T cell-dependent immunity against murine salmonellosis. PLOS Pathogens. 2023;19(9):10.1371/journal.ppat.1011666

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

Groom JR, Vince JE. IL-1α-releasing TH17 cells live long and prosper. Nature Immunology. 2023;24(2):10.1038/s41590-022-01412-x

View all publications

Lab research projects

Chemokine control of T cell host defence and memory

A defining feature of immunity is the acquisition and maintenance of immunological memory, which confers enhanced protection against pathogens.

Exploiting this, vaccine development has saved the lives of millions worldwide. Despite successes, considerable challenges remain for the development of vaccines against a number of recalcitrant viral infections of global importance.

This study investigates the cellular players and interactions that determine fate T cell fate decisions between effector and memory formation and will reveal how cellular positioning influences the maintenance and function of memory responses.

Project resources:
Duckworth DC, Lafouresse F, Wimmer VC, Broomfield BJ, Alexandre YO, Sheikh AA, Qin RZ, Alvarado C, Mielke LA, Pellegrini M, Mueller SN, Boudier T, Rogers KL, Groom JR. Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands. Nat Immunol 2021 Apr;22(4):434-448. PMID: 33649580

Duckworth BC, Groom JR. Conversations that count: Cellular interactions that drive T cell fate. Immunol Rev 2021 Mar:300(1):203-219. PMID: 33586207

Kelly HG, Tan HX, Juno JA, Esterbauer R, Ju Y, Jiang W, Wimmer VC, Duckworth BC, Groom JR, Caruso F, Kanekiyo M, Kent SJ, Wheatley AK. Self-assembling influenza nanoparticle vaccines drive extended germinal center activity and memory B cell maturation. JCI Insight 2020 May 21:5(10)e:136653. PMID: 32434990

Marsman C, Lafouresse F, Liao Y, Baldwin TM, Mielke LA, Hu Y, Mack M, Hertzog PJ, de Graaf CA, Shi W, Groom JR. Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation. Immunol Cell Biol. 2018 Nov;96(10):1083-1094. PMID: 29870118.

Groom JR, Richmond J, Murooka TT, Sorensen EW, Sung JH, Bankert K, von Andrian UH, Moon JJ, Mempel TR, Luster AD. CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity. 2012 Dec 14;37(6):1091-103. PMID: 23123063.

Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity.