Dr Geraldine O'Connor

Lecturer in Biomedical Sciences & and Programme Leader, BSc Biology

While studying for a degree in Biochemistry in Trinity College Dublin I developed an avid interest in the human immune system and stayed on to do a PhD in Immunology within the School of Biochemistry and Immunology. Since then I have worked on various aspects of the human immune system including research on human immunodeficiency (both genetic and acquired), and in understanding how differences between individuals impacts their immune function and ultimately their health.


After completion of my PhD in Dublin, I spend six years as a postdoctoral fellow at the National Cancer Institute within the NIH in the US. I then moved to Australia where I worked as a research fellow in the Department of Microbiology and Immunology at the University of Melbourne.


I have contributed to teaching in a variety of areas including Biochemistry and Molecular Biology, Biochemistry in Animal Systems, Biomolecules and Cells, and Biotechnology. At the University of Chester, I am involved in teaching of modules including Medical Microbiology and Infection Control (BI6114), Cellular and Molecular Pathology (BI6128), Introductory Microbiology and Immunology (BI4113,) and Biology of Disease (BI5111).


My research interests are centred on understanding the function and activation of the human innate immune system, and in particular on the role of the Natural Killer (NK) cells. NK cells are lymphocytes found in the peripheral blood and in many tissues. Their job is to assist in the elimination of microbial infections and in the prevention of tumours.  As part of the innate immune system, NK cells can rapidly identify and respond to immune challenges, and can function to eliminate infected or cancerous cells. In addition, they communicate with other immune cells to coordinate an appropriate immune response. 

Perturbations to Natural Killer Cell Function in Disease

NK cells are an important component of our immune systems. This is evidenced by those rare conditions in which individuals specifically lack NK cells, which results in recurrent viral and bacterial infections. One research area of interest is to understand how NK cell function can be lost or altered in disease conditions. This includes genetic disorders where certain NK cell components are lacking as well as in infections (e.g. HIV) or cancer, where the conditions in the body result in decreased or altered NK cell function. An understanding of the mechanism of NK cell dysfunction would allow for the design of appropriate intervention strategies. 

How Genetic Differences Impacts Protein Function and Immune Outcome

The way in which NK cells are activated is complex, and involves the integration of inputs from a variety of cell surface receptors. One such family of receptors is the Killer Cell Immunoglobulin-like Receptors (KIR). These receptors are found on Natural Killer and T cells and are thus well positioned to control both innate and adaptive immune responses. These receptors, which interact with the highly polymorphic HLA molecules, are themselves high variable. My work had explored the functional consequences of the genetic variation seen within this family – how this impacts on protein structure and expression, cell surface levels, as well as interaction with their HLA ligands.

Ultimately, these changes at the genetic level may impact protein behaviour and thus NK cell function and the outcome of immune challenges. To explore this, I am interesting in identifying cohorts of patients with various infection diseases or cancer, and examining the role of NK (and T cell) function and disease outcome with reference to the particular KIR variant present in each individual.

Killer Immunoglobulin-like Receptors in Cancer

The function of Killer Immunoglobulin-like Receptors is best understood in NK cells, but in healthy individuals a small proportion of T cells also express KIR, which may influence their function. In contrast to the low expression on healthy T cells, in a number of pathological conditions KIR expression on T cells is increased. I am interested in exploring the expression of KIR on cancers derived from T cells, and exploring how KIR expression may be contributing to initiation and/or progression of cancer. Identification of the role of KIR in these cancers may identify an additional target for cancer therapies.


Figure 1: Identification of Natural Killer Cells by Flow Cytometry

NK cells can be identified from peripheral blood by first identifying the lymphocyte population (based on their light scattering
properties). In this donor 17.5% of the blood cells are lymphocytes. Within the lymphocyte population, NK cells are identifies by their expression of the antigen CD56, in the absence of CD3 (in this donor 10.3% of the lymphocytes).  
Dr Geraldine O'Connor - Research Project


Figure 2: The Role of Polymorphic Position in KIR-ligand Interaction

An understanding of the positions involved in interaction of KIR (in blue) with its HLA ligand (green) generates a framework to
understand how changes in the protein sequence (e.g. position W283 as highlighted) that are found in different individuals may impact on protein function. 
Dr Geraldine O'Connor - Research Project

Figure 3: KIR associate with specific signalling molecule to mediate their functional effects.

Immunoprecipitation and Western Blotting techniques can be used to analyse the ability of KIR variants to associated with specific signalling molecules. 
Dr Geraldine O'Connor - Research Project

Figure 4: Fluorescent Microscopy Reveals Cellular localis ation of Immune ReceptorsDr Geraldine O'Connor - Research Project


Please email me for further information.

Published work

Burg, A. R., Quigley, L., Jones, A. V., O'Connor, G. M., Boelte, K., McVicar, D. W., & Orr, S. J. (2016). Orally administered beta-glucan attenuates the Th2 response in a model of airway hypersensitivity. Springerplus, 5(1), 815. doi:10.1186/s40064-016-2501-1

Saunders PM, Pymm P, Pietra G, Hughes VA, Hitchen C, O'Connor GM, Loiacono F, Widjaja J, Price DA, Falco M, Mingari MC, Moretta L, McVicar DW, Rossjohn J, Brooks AG, Vivian JP. Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition. J Exp Med. 2016 May 2;213(5):791-807. 

De Ravin SS, Wu X, Moir S, Anaya-O'Brien S, Kwatemaa N, Littel P, Theobald N, Choi U, Su L, Marquesen M, Hilligoss D, Lee J, Buckner CM, Zarember KA, O'Connor G, McVicar D, Kuhns D, Throm RE, Zhou S, Notarangelo LD, Hanson IC, Cowan MJ, Kang E, Hadigan C, Meagher M, Gray JT, Sorrentino BP, Malech HL. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med. 2016 Apr 20;8(335):335ra57. 

O'Connor GM, Vivian JP, Gostick E, Pymm P, Lafont BA, Price DA, et al. Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1. J Virol. 2015;89(10):5213-21. 

Augusto DG, O'Connor GM, Lobo-Alves SC, Bass S, Martin MP, Carrington M, et al. Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo. Eur J Immunol. 2015;45(7):2052-60. 

Townsley E, O'Connor G, Cosgrove C, Woda M, Co M, Thomas SJ, et al. Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells. Clin Exp Immunol. 2015. 

Saunders PM, Vivian JP, O'Connor GM, Sullivan LC, Pymm P, Rossjohn J, et al. A bird's eye view of NK cell receptor interactions with their MHC class I ligands. Immunol Rev. 2015;267(1):148-66.

Saunders PM, Vivian JP, Baschuk N, Beddoe T, Widjaja J, O'Connor GM, et al. The interaction of KIR3DL1*001 with HLA class I molecules is dependent upon molecular microarchitecture within the Bw4 epitope. J Immunol. 2015;194(2):781-9. 

O'Connor GM, Vivian JP, Gostick E, Pymm P, Lafont BA, Price DA, et al. Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1. J Virol. 2015;89(10):5213-21. 

Augusto DG, O'Connor GM, Lobo-Alves SC, Bass S, Martin MP, Carrington M, et al. Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo. Eur J Immunol. 2015;45(7):2052-60. 

Wright PW, Li H, Huehn A, O'Connor GM, Cooley S, Miller JS, et al. Characterization of a weakly expressed KIR2DL1 variant reveals a novel upstream promoter that controls KIR expression. Genes Immun. 2014;15(7):440-8. 

O'Connor GM, Vivian JP, Widjaja JM, Bridgeman JS, Gostick E, Lafont BA, et al. Mutational and structural analysis of KIR3DL1 reveals a lineage-defining allotypic dimorphism that impacts both HLA and peptide sensitivity. J Immunol. 2014;192(6):2875-84. 

Orr SJ, Burg AR, Chan T, Quigley L, Jones GW, Ford JW, et al. LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-gamma production by repressing beta-catenin activation in dendritic cells. PLoS Pathog. 2013;9(5):e1003357. 

O'Connor GM, McVicar D. The yin-yang of KIR3DL1/S1: molecular mechanisms and cellular function. Crit Rev Immunol. 2013;33(3):203-18. 

Chaigne-Delalande B, Li FY, O'Connor GM, Lukacs MJ, Jiang P, Zheng L, et al. Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D. Science. 2013;341(6142):186-91. 

O'Connor GM, Seich Al Basatena NK, Olavarria V, MacNamara A, Vine A, Ying Q, et al. In contrast to HIV, KIR3DS1 does not influence outcome in HTLV-1 retroviral infection. Hum Immunol. 2012;73(8):783-7. 

Vivian JP, Duncan RC, Berry R, O'Connor GM, Reid HH, Beddoe T, et al. Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B. Nature. 2011;479(7373):401-5.

O'Connor GM, Yamada E, Rampersaud A, Thomas R, Carrington M, McVicar DW. Analysis of binding of KIR3DS1*014 to HLA suggests distinct evolutionary history of KIR3DS1. J Immunol. 2011;187(5):2162-71. 

Fadda L, O'Connor GM, Kumar S, Piechocka-Trocha A, Gardiner CM, Carrington M, et al. Common HIV-1 peptide variants mediate differential binding of KIR3DL1 to HLA-Bw4 molecules. J Virol. 2011;85(12):5970-4.

Thomas R, Apps R, Qi Y, Gao X, Male V, O'HUigin C, et al. HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C. Nat Genet. 2009;41(12):1290-4.O'Connor GM, Vivian JP, Gostick E, Pymm P, Lafont BA, Price DA, et al. Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1. J Virol. 2015;89(10):5213-21.