Joanna Groom-Projects

Joanna Groom-Projects

Researcher: 

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. 

Team members 
Fanny Lafouresse, Brigette Duckworth in collaboration with Gabrielle Belz (Molecular Immunology), Marc Pellegrini (Infection and Immunity), Kelly Rogers (Centre for Dynamic Imaging), Laura Mackay and Scott Mueller (University of Melbourne).

Project references 
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.

Sung JH, Zhang H, Moseman EA, Alvarez D, Iannacone M, Henrickson SE, de la Torre JC, Groom JR, Luster AD, von Andrian UH. Chemokine guidance of central memory T cells is critical for antiviral recall responses in lymph nodes. Cell. 2012 Sep 14;150(6):1249-63. PMID: 22980984.

Groom JR. Moving to the suburbs: T-cell positioning witin lymph nodes during activation and memory. Immunol Cell Biol. 2015 Apr;93(4):330-6. PMID: 25753266

Multiple paths of TFH differentiation and their impact on B cell protection against infection

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. 

Team members 

Amania Sheikh in collaboration with Gabrielle Belz, Stephen Nutt (Molecular Immunology), Wei Shi (Bioinformatics) and Kelly Rogers (Centre for Dynamic Imaging), Kim Jacobson (Monash University) and Katherine Kedzierska (University of Melbourne)

Project references
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.

Piovesan 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

Good-Jacobson KL, Groom JR. Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators that Drive the Creation and Collusion of Autoreactive Lymphcytes. Front Immunol. 2018 Mar 8;9:482. PMID: 29568300

Modulation of immune responses by the immunosuppression

Our immune system exists on a knife-edge; balancing inflammatory responses to overcome infection and cancer, with the risk of autoimmunity and immune pathology. 

The termination of immune responses plays a critical role in dampening inflammation leading to the establishment of memory following pathogen clearance. 

The balance between these outcomes needs to be tightly regulated. This project reveals the biology of a new facilitator of terminal immune responses that lead to enhanced memory. 

Understanding novel immunosuppressive mechanisms will reveal therapeutic strategies that limit immune pathology and drive protective memory.

Team members

Lisan Kuijper in collaboration with Marco Herold (Molecular Genetics of Cancer).