PhD (Otago) BMedSc(Hons) (VUW)
Dr Lisa Connor completed her PhD at the Malaghan Institute of Medical Research with A.Prof Jo Kirman and post-doctoral fellowship at the Trudeau Institute, NY, USA, focused on vaccination against respiratory diseases tuberculosis and influenza.
After returning to New Zealand in 2012, her research interests turned to dendritic cells, a major target for vaccine development and investigated dendritic cell instruction of immune cell fate with Prof. Franca Ronchese at the Malaghan Institute of Medical Research. In 2017 she was awarded a Sir Charles Hercus fellowship from the Health Research Council of New Zealand to examine the impact of the tissue microenvironment on Dendritic cell function. In 2018 Dr Connor established her research lab in the School of Biological Sciences at Victoria University of Wellington.
I am a cellular immunologist with an interest in the host-pathogen interface. Our immune systems play a remarkable role in the defence against microscopic villains, and can orchestrate a faster superior response upon re-exposure, which is the basis of vaccination. Our research focus is to investigate novel vaccines that promote potent humoral and cellular immunity in the respiratory tract – a site where many pathogens try to invade.
Contributors – Ian Hermans, Gavin Painter, Theresa Pankhurst, Kaitlin Buick, Olga Palmer, Joshua Lange, Benji Compton, Sarah Draper
Over 90% of pathogens invade the human host through mucosal routes. As a result, our immune system has created a specialised mucosal immune response, armoured with cells and immunoglobulins (Ig) designed to defend mucosal surfaces. Such defences include production of secretory IgA (SIgA), which block pathogen invasion, and the presence of long-lived tissue resident memory T cells. Despite the specialised role of mucosal immunity, the majority of human vaccines are administered parenterally and fail to elicit mucosal immune responses.
New vaccine designs are moving away from whole cell-based approaches. Instead, the less immunogenic subunit vaccines that require an “adjuvant” - compounds added to a vaccine that specifically enhance induction of adaptive immune responses, are favoured. This poses a significant barrier for mucosal vaccines as 1) many adjuvant formulations are not appropriate for mucosal delivery; 2) mucosal surfaces act as a physical barrier that can prevent effective access to the target immune cells. We propose that we can overcome the current barriers for mucosal vaccine development by designing adjuvants that target innate-like T cells located in the mucosal tissue. In collaboration with Prof Ian Hermans, MIMR, Prof Gavin Painter, Ferrier Research Institute and Avalia Immunotherapies we are designing and testing novel mucosal vaccines for influenza virus.
Contributors – Davide Comoletti, Cynthia Morgan, Liam Turk.
Communication between dendritic cells (DC) and T cells is essential for activating the adaptive immune response. Information passed on from the DC to the T cell is typically mediated by receptor-ligand interactions. As a result, proteins expressed at the DC T cell interface provide an attractive target for therapeutic intervention. DCs are well-known for their ability to sense their environment, and in turn instruct T cells to respond most appropriately to a given situation. However, in the case of allergy, T cells (following instruction by DCs) inappropriately target harmless substances and differentiate into T helper (Th) 2 cells. This project explores receptor ligand interactions that occur between DCs and T cells. In collaboration with VUW molecular protein biologist, Dr Davide Comoletti, we are developing a high-throughput screen that has the capacity to go beyond a single interacting pair and feasibly screen >80,000 interactions. The ultimate goal of this screen is to identify novel protein-protein interactions between DC and T cells and determine key molecules involved in Th2 development.
Blecher-Gonen R, Bost P, Hilligan KL, David E, Salame TM, Roussel E, Connor LM, Mayer JU, Bahar Halpern K, Tóth B, Itzkovitz S, Schwikowski B, Ronchese F, Amit I (2019) Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity. Cell Systems 8(2):109-121.e6
Pellefigues C, Tang SC, Schmidt A, White RF, Lamiable O, Connor LM, Ruedl C, Dobrucki J, Le Gros G, Ronchese F (2017) Toll-Like Receptor 4, but Not Neutrophil Extraceullular Traps, Promote IFN Type I Expression to Enhance Th2 Responses to Nippostrongylus brasiliensis. Front Immunol 8:1575
Connor LM, Tang SC, Cognard E, Ochiai S, Hilligan KL, Old SI, Pellefigues C, White RF, Patel D, Smith AA, Eccles DA, Lamiable O, McConnell MJ, Ronchese F. (2017) Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles. J Exp Med.
Hilligan KL, Connor LM, Schmidt AJ, Ronchese F (2016) Activation-Induced TIM-4 Expression Identifies Differential Responsiveness of Intestinal CD103+ CD11b+ Dendritic Cells to a Mucosal Adjuvant. PLoS One
Connor LM, Tang SC, Camberis M, Le Gros G, Ronchese F (2014) Helminth–conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo. J. Immunol
Connor LM, Tang SC, Camberis M, Le Gros G, Ronchese F (2014) Helminth–conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo. J. Immunol.