A5006051512- Neuroblastoma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Neonatal Health and Biochemistry
- Rheumatoid Arthritis Research and Therapies
- Immunotherapy and Immune Responses
- Childhood Cancer Survivors' Quality of Life
- Biochemical and Molecular Research
- Advanced Biosensing Techniques and Applications
- ATP Synthase and ATPases Research
- Polyamine Metabolism and Applications
- 14-3-3 protein interactions
- Bacteriophages and microbial interactions
- Multiple Sclerosis Research Studies
- PARP inhibition in cancer therapy
- Chronic Myeloid Leukemia Treatments
- Galectins and Cancer Biology
- Chromatin Remodeling and Cancer
UNSW Sydney
2016-2025
Cancer Institute of New South Wales
2019-2024
Children's Cancer Institute Australia
2016-2023
Ablynx (Belgium)
2021
Hasselt University
2008-2016
Transnational University Limburg
2007-2010
Colorado State University
2003
Abstract Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better safer treatments for acute urgently needed, standard drug development pipelines lengthy repurposing therefore provides promising approach. Our previous evaluation FDA-approved drugs their antileukemic activity identified disulfiram, used the treatment alcoholism, as candidate hit compound. This study...
High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects therapy. Drug encapsulation into liposomal nanocarriers shown clinical success at improving biodistribution tolerability chemotherapy. However, enhancements in drug efficacy have been limited lack selectivity the formulations for cancer cells. Here, we report on generation bispecific antibodies (BsAbs) with dual binding to leukemic cell receptor, such as CD19, CD20, CD22, or CD38, methoxy...
Around 10% of acute leukemias harbor a rearrangement the MLL/KMT2A gene, and presence this translocation results in highly aggressive, therapy‐resistant leukemia subtype with survival rates below 50%. There is high unmet need to identify safer more potent therapies for MLL‐rearranged (MLL‐r) that can be combined established chemotherapeutics decrease treatment‐related toxicities. The curaxin, CBL0137, has demonstrated nongenotoxic anticancer chemopotentiating effects number preclinical...
Abstract An important contribution of B cells and autoantibodies has been demonstrated in the pathogenesis multiple sclerosis (MS), leading to interest use such as diagnostic or prognostic biomarkers. The objective this study was identify novel Ab biomarkers for MS using “serological Ag selection”. Using a phage display library derived from brain plaques, we applied serological selection antigenic targets specifically interacting with Abs present cerebrospinal fluid (CSF) 10...
Abstract High-risk neuroblastomas, often associated with MYCN oncogene amplification, are addicted to polyamines, small polycations vital for cellular functioning. We have shown that neuroblastoma cells increase polyamine uptake when exposed the biosynthesis inhibitor DFMO, currently in clinical trial, and this mechanism limits efficacy of drug. While finding resulted development transport inhibitors including AMXT 1501, presently under investigation combination mechanisms transporters...
We investigated whether targeting chromatin stability through a combination of the curaxin CBL0137 with histone deacetylase (HDAC) inhibitor, panobinostat, constitutes an effective multimodal treatment for high-risk neuroblastoma.The effects drug on cancer growth were examined in vitro and animal models MYCN-amplified neuroblastoma. The molecular mechanisms action analyzed by multiple techniques including whole transcriptome profiling, immune deconvolution analysis, immunofluorescence, flow...
Improving the poor prognosis of infant leukaemias remains an unmet clinical need. This disease is a prototypical fusion oncoprotein-driven paediatric cancer, with MLL (KMT2A)-fusions present in most cases. Direct targeting these driving oncoproteins represents unique therapeutic opportunity. rationale led us to initiate drug screening aim discovering drugs that can block MLL-fusion oncoproteins.A screen for inhibition proteins was developed overcomes traditional limitations transcription...
Objectives. Despite recent progress in biomarker discovery for RA diagnostics, still over one-third of patients—and even more early disease—present without RF or ACPA. The aim this study was to confirm the presence previously identified autoantibodies novel Hasselt University (UH) peptides and seronegative RA. Methods. Screening antibodies against UH UH-RA.1, UH-RA.9, UH-RA.14 UH-RA.21, performed two large independent cohorts. Peptide ELISAs were developed screen UH-RA peptides. First, 292...
Abstract The ability of the N-MYC transcription factor to drive cancer progression is well demonstrated in neuroblastoma, most common extracranial pediatric solid tumor, where MYCN amplification heralds a poor prognosis, with only 11% high-risk patients surviving past 5 years. However, decades attempts direct inhibition or its paralogues has led conclusion that this protein “undruggable.” Therefore, targeting pathways upregulated by signaling presents an alternative therapeutic approach....
Rearrangements of the Mixed Lineage Leukemia (MLL/KMT2A) gene are present in approximately 10% acute leukemias and characteristically define disease with poor outcome. Driven by unmet need to develop better therapies for KMT2A-rearranged leukemia, we previously discovered that novel anti-cancer agent, curaxin CBL0137, induces decondensation chromatin cancer cells, delays leukemia progression potentiates standard care chemotherapies preclinical models. Based on promising potential histone...
Survival rates for pediatric patients suffering from mixed lineage leukemia (MLL)-rearranged remain below 50% and more targeted, less toxic therapies are urgently needed. A screening method optimized to discover cytotoxic compounds selective MLL-rearranged identified CCI-006 as a novel inhibitor of CALM-AF10 translocated leukemias that share common leukemogenic pathways. inhibited mitochondrial respiration induced membrane depolarization apoptosis in subset (7/11, 64%) cell lines within few...
Epithelial ovarian cancer (EOC) is a complex disease comprising discrete histological and molecular subtypes, for which survival rates remain unacceptably low. Tailored approaches this deadly heterogeneous are urgently needed. Efflux pumps belonging to the ATP-binding cassette (ABC) family of transporters known roles in both drug resistance biology also highly targetable. Here we have investigated association ABCC4/MRP4 expression clinical outcome its biological function endometrioid serous...
There is an urgent need for the development of less toxic, more selective and targeted therapies infants with leukemia characterized by translocation mixed lineage (MLL) gene. In this study, we performed a cell-based small molecule library screen on infant MLL-rearranged (MLL-r) cell line, PER-485, in order to identify inhibitors MLL-r leukemia. After screening initial hits cytotoxic effect against panel 30 lines including MLL wild-type (MLL-wt) leukemia, solid tumours control cells, CCI-007...
Abstract : We applied a cDNA phage display method called serological antigen selection (SAS) to identify immunogenic targets that evoke an autoantibody response in the serum of multiple sclerosis (MS) patients. This involves expression library, this study MS brain on filamentous and subsequent using patient immunoglobulin G (IgG). To apply SAS technology for autoantibodies patients, optimization was necessary deplete products encode IgG fragments derived from B cells present plaques....
A major focus in rheumatoid arthritis (RA) research is the identification of antigens that are targeted by joint‐directed autoimmune response. B cells and associated autoantibodies have been studied RA to identify antigenic targets discover RA‐associated which can be used as disease markers. This indicated heterogeneity autoantibody profile large overlap antibody specificities with other rheumatic diseases pointing toward need for multiplexing an profile. The discovery antibodies directed...
Increasing evidence indicates an involvement of B cells in multiple sclerosis (MS). However, little is known about antigenic targets recognized by antibodies present blood and cerebrospinal fluid (CSF) MS patients. This study was therefore aimed at identifying the antigen reactivity CSF compares identified antibody profile with that serum same patient using cDNA phage display. Selection rounds on paired this 13 which 5 were enriched 2 antibodies. Interestingly, six remaining shown to be both...
Phage display is a powerful technique that enables easy identification of targets for any type ligand. Targets are displayed at the phage surface as fusion protein to one coat proteins. By means repeated process affinity selection on ligand, specific enrichment will occur. In our studies using C-terminal cDNA fragments p6, we noticed occasional do not contain an open reading frame. This event has previously been described in other N-terminal proteins and was due uncommon translational events...
Patients whose leukemias harbor a rearrangement of the Mixed Lineage Leukemia (MLL/KMT2A) gene have poor prognosis, especially when disease strikes in infants. The clinical outcome linked to this aggressive and detrimental treatment side-effects, particularly children, warrant urgent development more effective cancer-selective therapeutics. aim study was identify novel candidate compounds that selectively target KMT2A-rearranged (KMT2A-r) leukemia cells. A library containing 3707 approved...