About
- Assay development through to validation for clinical trial…
Activity
- Professor Rajiv Khanna AO and his team have developed super-charged immune cells to fight #glioblastoma, a highly aggressive and difficult to treat…
Professor Rajiv Khanna AO and his team have developed super-charged immune cells to fight #glioblastoma, a highly aggressive and difficult to treat…
Liked by Laverne Robilliard, PhD
- Exceptional early-career brain cancer researcher Dr Susan Li, University of Auckland, has been awarded a Neurological Foundation First Fellowship…
Exceptional early-career brain cancer researcher Dr Susan Li, University of Auckland, has been awarded a Neurological Foundation First Fellowship…
Liked by Laverne Robilliard, PhD
- Congratulations to Dr Maize Cao, University of Auckland, who’s just been awarded $15,000 for her project identifying common features of amyotrophic…
Congratulations to Dr Maize Cao, University of Auckland, who’s just been awarded $15,000 for her project identifying common features of amyotrophic…
Liked by Laverne Robilliard, PhD
Experience & Education
Publications
Comprehensive analysis of inhibitory checkpoint ligand expression by glioblastoma cells
Immunology and Cell Biology
See publicationGlioblastoma is a highly aggressive brain malignancy commonly refractory to classical and novel chemo-, radio- and immunotherapies, with median survival times of ~15 months following diagnosis. Poor immunological responses exemplified by the downregulation of T-cell activity, and upregulation of immunosuppressive cells within the tumor microenvironment have limited the effectiveness of immunotherapy in glioblastoma to date. Here we show that glioblastoma cells express a large repertoire of…
Glioblastoma is a highly aggressive brain malignancy commonly refractory to classical and novel chemo-, radio- and immunotherapies, with median survival times of ~15 months following diagnosis. Poor immunological responses exemplified by the downregulation of T-cell activity, and upregulation of immunosuppressive cells within the tumor microenvironment have limited the effectiveness of immunotherapy in glioblastoma to date. Here we show that glioblastoma cells express a large repertoire of inhibitory checkpoint ligands known to control effector T cell responses. Furthermore, flow cytometry analysis reveals that glioblastoma cells with an enhanced stem cell-like phenotype express several investigated ligands at significant levels on their cell surface. This reveals that glioblastoma stem-like cells express suppressive ligands with the potential of suppressing major T cell checkpoint receptors. With this information, it is now essential that we understand the relevance of this extensive repertoire of immune checkpoint ligands and their functional consequence on immune evasion in glioblastoma. This is necessary to develop effective immunotherapeutics and to be able to match treatment to patient, especially in the light of CheckMate 143.
Analysis of Melanoma Secretome for Factors That Directly Disrupt the Barrier Integrity of Brain Endothelial Cells
International Journal of Molecular Sciences
See publicationWe have recently demonstrated that invasive melanoma cells are capable of disrupting the brain endothelial barrier integrity. This was shown using ECIS biosensor technology, which revealed rapid disruption via the paracellular junctions. In this paper, we demonstrate that melanoma cells secrete factors (e.g., cytokines) that weaken the endothelial barrier integrity. Through proteome profiling, we attempt to identify the barrier-disrupting cytokines. Melanoma conditioned media were collected…
We have recently demonstrated that invasive melanoma cells are capable of disrupting the brain endothelial barrier integrity. This was shown using ECIS biosensor technology, which revealed rapid disruption via the paracellular junctions. In this paper, we demonstrate that melanoma cells secrete factors (e.g., cytokines) that weaken the endothelial barrier integrity. Through proteome profiling, we attempt to identify the barrier-disrupting cytokines. Melanoma conditioned media were collected from three New Zealand melanoma lines. ECIS technology was used to assess if the conditioned media disrupted the endothelial barrier independent of the melanoma cells. The melanoma cell secretome was assessed using cytometric bead array (CBA), Luminex immunoassay and multiplex Proteome Profilers, to detect the expression of secretory proteins, which may facilitate metastasis. Finally, ECIS technology was used to assess the direct effects of secreted proteins identified as candidates from the proteome screens. We show that melanoma-conditioned media significantly disrupted the brain endothelial barrier, however, to a much lesser extent than the cells from which they were collected. Cytokine and proteome profiling of the conditioned media showed evidence of high concentrations of approximately 15 secreted proteins (including osteopontin, IL-8, GDF-15, MIF and VEGF). These 15 secreted proteins were expressed variably across the melanoma lines. Surprisingly, the addition of these individually to the brain endothelial cells did not substantially affect the barrier integrity. ANGPTL-4 and TGFβ were also produced by the melanoma cells. Whilst TGFβ-1 had a pronounced effect on the barrier integrity, surprisingly ANGPTL-4 did not. However, its C-terminal fragment did and within a very similar period to the conditioned media, albeit not to the same extent. Herein we show that melanoma cells produce a wide-range of soluble factors at high concentrations...
The Importance of Multifrequency Impedance Sensing of Endothelial Barrier Formation Using ECIS Technology for the Generation of a Strong and Durable Paracellular Barrier
Biosensors
See publicationIn this paper, we demonstrate the application of electrical cell-substrate impedance sensing (ECIS) technology for measuring differences in the formation of a strong and durable endothelial barrier model. In addition, we highlight the capacity of ECIS technology to model the parameters of the physical barrier associated with (I) the paracellular space (referred to as Rb) and (II) the basal adhesion of the endothelial cells (α, alpha). Physiologically, both parameters are very important…
In this paper, we demonstrate the application of electrical cell-substrate impedance sensing (ECIS) technology for measuring differences in the formation of a strong and durable endothelial barrier model. In addition, we highlight the capacity of ECIS technology to model the parameters of the physical barrier associated with (I) the paracellular space (referred to as Rb) and (II) the basal adhesion of the endothelial cells (α, alpha). Physiologically, both parameters are very important for the correct formation of endothelial barriers. ECIS technology is the only commercially available technology that can measure and model these parameters independently of each other, which is important in the context of ascertaining whether a change in overall barrier resistance (R) occurs because of molecular changes in the paracellular junctional molecules or changes in the basal adhesion molecules. Finally, we show that the temporal changes observed in the paracellular Rb can be associated with changes in specific junctional proteins (CD144, ZO-1, and catenins), which have major roles in governing the overall strength of the junctional communication between neighbouring endothelial cells.
ECIS technology reveals that monocytes isolated by CD14+ ve selection mediate greater loss of BBB integrity than untouched monocytes, which occurs to a greater extent with IL-1β activated endothelium in comparison to TNFα
PloS one
See publicationBackground: We have previously shown that TNFα and IL-1β differentially regulate the inflammatory phenotype of human brain endothelial cells (hCMVECs). In this regard, IL-1β treatment was considerably more potent than TNFα at increasing expression of inflammatory chemokines and leukocyte adhesion molecules. We therefore hypothesised that interaction of the hCMVECs with human monocytes would also be dependent on the activation status of the endothelium. Therefore, the primary aim of this study…
Background: We have previously shown that TNFα and IL-1β differentially regulate the inflammatory phenotype of human brain endothelial cells (hCMVECs). In this regard, IL-1β treatment was considerably more potent than TNFα at increasing expression of inflammatory chemokines and leukocyte adhesion molecules. We therefore hypothesised that interaction of the hCMVECs with human monocytes would also be dependent on the activation status of the endothelium. Therefore, the primary aim of this study was to assess whether brain endothelial cells activated by IL-1β or TNFα differed in their interaction with monocytes.
Courses
Doctoral Academic Leadership Initiative Scholarship (2020)
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Honors & Awards
Neurological Women in Neuroscience Panelist
Neurological Foundation of New Zealand
Inaugural Hilary Holloway Image Trophy for best image, and 1st in Confocal Microscopy Award.
BIRU, University of Auckland
Neurological Foundation W & B Miller Postgraduate Scholarship
Neurological Foundation of New Zealand
A fully funded PhD scholarship worth $106,755 NZD
Catwalk Trust Summer Studentship ($6000)
CatWalk Trust
A studentship to supplement a summer internship at the University of Auckland
Neurological Foundation Full Project Grant (Named Investigator)
Neurological Foundation of New Zealand
Neurological Foundation Travel Grant
Neurological Foundation of New Zealand
Assistance to attend EANO 2019 (Lyon, France from the 19th – 22nd of September 2019) and ESMO congress 2019 (Barcelona, Spain from the 27th – 1st of October 2019) ($4,200)
Neurological Foundation of New Zealand Small Project Grant (named investigator)
Neurological Foundation of New Zealand
Organizations
University of Auckland
Graduate Teaching Assistant
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More activity by Laverne
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- 🚨 Last chance for early bird registration for the Australasian Winter Conference on Brain Research (AWCBR)—closing on 19 July! 🚨 Don't miss out on…
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- 🎙️ Thrilled to share my recent chat with Charles Beasley on the "Good Clinical" podcast! We dived into some exciting findings from my research on…
🎙️ Thrilled to share my recent chat with Charles Beasley on the "Good Clinical" podcast! We dived into some exciting findings from my research on…
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- Inspiration filled the air at the 30th anniversary celebration of the Neurological Foundation Human Brain Bank last week. More than 240 people were…
Inspiration filled the air at the 30th anniversary celebration of the Neurological Foundation Human Brain Bank last week. More than 240 people were…
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- Thanks to our fantastic Personal Awards Committee experts who’ve spent the day assessing applications for fellowships. Their deep insights and…
Thanks to our fantastic Personal Awards Committee experts who’ve spent the day assessing applications for fellowships. Their deep insights and…
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- Wonderful to see Dr Emma Scotter appointed a Member of the New Zealand Order of Merit for outstanding services to motor neuron disease (MND) research…
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