A5088201972- Monoclonal and Polyclonal Antibodies Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Click Chemistry and Applications
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Chemical Synthesis and Analysis
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- SARS-CoV-2 and COVID-19 Research
- Diabetes Treatment and Management
- Glycosylation and Glycoproteins Research
- Autophagy in Disease and Therapy
- Occupational and environmental lung diseases
- Economic and Financial Impacts of Cancer
- Cytokine Signaling Pathways and Interactions
- Cancer Cells and Metastasis
- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Pancreatic function and diabetes
- Advanced Glycation End Products research
- Viral-associated cancers and disorders
Monash University
2018-2025
Australian Regenerative Medicine Institute
2018-2025
Discovery Institute
2019
Bristol-Myers Squibb (United States)
2019
Black AIDS Institute
2019
Centro Medico Nacional Siglo XXI
2014
St Vincents Institute of Medical Research
2011
The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. peptide repertoire is extended various posttranslational modifications, including proteasomal splicing fragments from distinct regions to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction the immunopeptidome constitutes such peptides; however, because computational limitations, not possible assess whether trans-spliced...
Neopeptide-based immunotherapy has been recognised as a promising approach for the treatment of cancers. For neopeptides to be by CD8+ T cells and induce an immune response, their binding human leukocyte antigen class I (HLA-I) molecules is necessary first step. Most epitope prediction tools thus rely on such binding. With use mass spectrometry, scale naturally presented HLA ligands that could used develop predictors expanded. However, there are rarely efforts focus integration these...
Abstract Antigen recognition by CD8+ T cells is governed the pool of peptide antigens presented on cell surface in context HLA class I complexes. Studies have shown not only a high degree plasticity immunopeptidome, but also that considerable fraction all peptides generated through proteasome-mediated splicing noncontiguous regions proteins to form novel antigens. Here, we used high-resolution mass spectrometry combined with new bioinformatic approaches characterize immunopeptidome melanoma...
Peptide vaccination remains a viable approach to induce T-cell mediated killing of tumors. To identify potential targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect pro-inflammatory cytokine interferon-γ (IFNγ) on transcriptome, proteome, and immunopeptidome TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, identified total 84,131 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I HLA-II alleles. Treatment with...
The presentation of post-translationally modified (PTM) peptides by cell surface HLA molecules has the potential to increase diversity targets for surveilling T cells. Although immunopeptidomics studies routinely identify thousands HLA-bound from lines and tissue samples, in-depth analyses proportion nature bearing one or more PTMs remains challenging. Here we have analyzed a variety allotypes assessed distribution mass spectrometry-detected PTMs, finding deamidation asparagine glutamine be...
Most COVID-19 vaccines elicit immunity against the SARS-CoV-2 Spike protein. However, protein mutations in emerging strains and immune evasion by virus demonstrates need to develop more broadly targeting vaccines. To facilitate this, we use mass spectrometry identify immunopeptides derived from seven relatively conserved structural non-structural proteins (N, E, Nsp1/4/5/8/9). We two different B-lymphoblastoid cell lines map Human Leukocyte Antigen (HLA) class I II immunopeptidomes covering...
Mesothelioma is an incurable, asbestos-exposure-related cancer that typically affects the lining or pleura of lungs. Symptoms develop many decades after initial asbestos exposure, leaving enduring legacy disease. The current disease burden peaking worldwide and thus there a massive unmet clinical need for curative therapies. Recently, immune checkpoint blockade-based therapy has been adopted as first-line treatment mesothelioma. Vaccine-induced augmentation responses unleashed during...
Ewing Sarcoma (EwS) is a rare pediatric malignancy characterized by unique t(11:22) (q24;q12) translocation resulting in the pathognomonic EWSR1::FLI1 fusion. Recent reports indicate that oncofusion drives aberrant expression of numerous transcripts, including Lipoxygenase Homology Domains 1 (LOXHD1). Given its highly restricted protein pattern and role EwS tumorigenesis metastasis, LOXHD1 may serve as novel immunotherapeutic target this malignancy. immunogenic epitopes to HLA-A*02:01...
Psoriasis vulgaris is a T cell-mediated autoimmune skin condition affecting around one in fifty people worldwide. Whilst advanced immunomodulatory therapeutic options have become available recent years, ongoing disease suppression still required with no curative treatment to date. The human leukocyte antigen class I allele HLA-C*06:02 the main genetic risk determinant of psoriasis. Its function present peptide antigens CD8+ cells and natural killer which turn elicit perpetuate immune...
Human islets are subjected to a number of stresses before and during their isolation that may influence survival engraftment after transplantation. Apoptosis is likely be activated in response these stresses. due intrinsic regulated by pro- antiapoptotic members the Bcl-2 family. While role family apoptosis rodent becoming increasingly understood, little known about which molecules expressed or required for human islets. This study investigated expression isolated RNA protein lysates were...
Introduction Diffuse intrinsic pontine glioma (DIPG), recently reclassified as a subtype of diffuse midline glioma, is highly aggressive brainstem tumor affecting children and young adults, with no cure median survival only 9 months. Conventional treatments are ineffective, highlighting the need for alternative therapeutic strategies such cellular immunotherapy. However, identifying unique tumor-specific cell surface antigens to target chimeric antigen receptor (CAR) or T-cell (TCR)...
XPO1 (Exportin-1/CRM1) is a nuclear export protein that frequently overexpressed in cancer and functions as driver of oncogenesis. Currently small molecules target are being used the clinic anticancer agents. We identify for natural killer (NK) cells. Using immunopeptidomics, we have identified peptide derived from can be recognized by activating NK cell receptor KIR2DS2 context human leukocyte antigen–C. The endogenously processed presented to activate cells specifically through this...
SARS-CoV-2 has caused a significant ongoing pandemic worldwide. A number of studies have examined the T cell mediated immune responses against SARS-CoV-2, identifying potential epitopes derived from proteome. Such will aid in targets for vaccination and monitoring. In this study, we applied tandem mass spectrometry proteomic techniques to library ∼40,000 synthetic peptides, order generate large dataset peptide MS/MS spectra. On basis, built an online knowledgebase, termed virusMS...
The p53 protein is mutated in more than 50% of human cancers. Mutated proteins not only lose their normal function but often acquire novel oncogenic functions, a phenomenon termed mutant gain-of-function. Mutant has been shown to affect the transcription range genes, as well protein-protein interactions with factors and other effectors; however, no one intensively investigated identified these proteins, or MHC presented epitopes, from viewpoint ability act targets for immunotherapeutic...
<title>Abstract</title> Most COVID-19 vaccines have been designed to elicit immunity against the SARS-CoV-2 Spike protein. However, repeated occurrence of new strains harbouring protein mutations demonstrates ready immune evasion by virus and pressing need develop more broadly targeting vaccines. To facilitate this, we used mass spectrometry identify immunopeptides that are derived from seven structural non-structural proteins relatively conserved across viral (N, E, Nsp1, Nsp4, Nsp5, Nsp8,...
Summary Antigen-recognition by CD8 + T cells is governed the pool of peptide antigens presented on cell surface in context HLA class I complexes. Recent studies have shown not only a high degree plasticity immunopeptidome, but also that considerable fraction all peptides generated through proteasome-mediated splicing non-contiguous regions proteins to form novel antigens. Here we used high-resolution mass-spectrometry combined with new bioinformatic approaches characterize immunopeptidome...
Abstract Natural killer (NK) cells are key components of the immune response to viral infections and cancer. Their functions controlled by activating inhibitory killer-cell immunoglobulin-like receptors (KIR) which have MHC class I ligands. KIR2DS2 is an KIR, that binds conserved peptides in context HLA-C has been associated with protective responses both cancer infections. We sought investigate whether NK can be specifically activated a peptide:MHC dependent manner generate functional as...
Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NODShiLt) mice, administered prediabetes (day 50-100) did not protect against T1D. decrease circulating AGEs or their precursors. Despite this,...
<div>Abstract<p>Antigen recognition by CD8<sup>+</sup> T cells is governed the pool of peptide antigens presented on cell surface in context HLA class I complexes. Studies have shown not only a high degree plasticity immunopeptidome, but also that considerable fraction all peptides generated through proteasome-mediated splicing noncontiguous regions proteins to form novel antigens. Here, we used high-resolution mass spectrometry combined with new bioinformatic...