Co-head, Leukaemia Translational Research
BPharm (Hons) MBA PhD
Laurence has a Bachelor of Pharmacy degree with First Class Honours and a MBA from Curtin University. In 2014, he completed his PhD studies at the Telethon Kids Institute in the area of haematopoiesis and paediatric leukaemia. He is currently supported by Children’s Leukaemia and Cancer Research Foundation and continues his research as a Senior Research Officer at Prof Kees’ Laboratory at the Telethon Kids Institute.
He is also working as a clinical trial governance pharmacist at Princess Margaret Hospital for Children and as a sessional academic at Curtin University and The University of Western Australia.
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Projects
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Publications
January 2022
Systematic In Vitro Evaluation of a Library of Approved and Pharmacologically Active Compounds for the Identification of Novel Candidate Drugs for KMT2A-Rearranged Leukemia
Patients whose leukemias harbor a rearrangement of the Mixed Lineage Leukemia (MLL/KMT2A) gene have a poor prognosis, especially when the disease strikes in infants. The poor clinical outcome linked to this aggressive disease and the detrimental treatment side-effects, particularly in children, warrant the urgent development of more effective and cancer-selective therapeutics.
Children's Cancers Published research Leukaemia Translational ResearchMay 2022The Bone Marrow Microenvironment in B-Cell Development and Malignancy
B lymphopoiesis is characterized by progressive loss of multipotent potential in hematopoi-etic stem cells, followed by commitment to differentiate into B cells, which mediate the humoral response of the adaptive immune system.
Children's Cancers Published research Leukaemia Translational ResearchMay 2022The Combination of Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Delays KMT2A-Rearranged Leukemia Progression
Rearrangements of the Mixed Lineage Leukemia (MLL/KMT2A) gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome.
Children's Cancers Published research Leukaemia Translational Research Subsite: CancerMarch 2021RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. Here, we show that Runt-related transcription factor 2 (RUNX2) was upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or an immature immunophenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism.
Children's Cancers Published research Leukaemia Translational Research Subsite: CancerApril 2021Exploiting the reactive oxygen species imbalance in high-risk paediatric acute lymphoblastic leukaemia through auranofin
The prognosis for high-risk childhood acute leukaemias remains dismal and established treatment protocols often cause long-term side effects in survivors. This study aims to identify more effective and safer therapeutics for these patients.
Children's Cancers Published research Leukaemia Translational ResearchApril 2021Preclinical Evaluation of Carfilzomib for Infant KMT2A-Rearranged Acute Lymphoblastic Leukemia
Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL.
Children's Cancers Published research Leukaemia Translational Research Subsite: Cancer Translational Genomics in LeukaemiaApril 2021Preclinical Evaluation of Carfilzomib for Infant KMT2A-Rearranged Acute Lymphoblastic Leukemia
Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL.
Children's Cancers Published research Leukaemia Translational ResearchJune 2021Therapeutic targeting of the leukaemia microenvironment
In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells.
Children's Cancers Published research Leukaemia Translational ResearchNovember 2021The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution
The bone marrow microenvironment plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression.
Children's Cancers Published research Academic Biostatistics Leukaemia Translational Research Systems VaccinologyNovember 2020Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia
Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding.
Children's Cancers Published research Leukaemia Translational Research Subsite: CancerNovember 2020The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution
The bone marrow microenvironment (BMM) plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression.
Children's Cancers Published research Leukaemia Translational Research Subsite: Cancer Translational Genomics in LeukaemiaJuly 2020Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-cell Leukemia
Children with Down syndrome (constitutive trisomy 21) that develop acute lymphoblastic leukemia (DS-ALL) have a 3-fold increased likelihood of treatment-related mortality coupled with a higher cumulative incidence of relapse, compared with other children with B-cell acute lymphoblastic leukemia (B-ALL).
Children's Cancers Published research Leukaemia Translational Research Subsite: Cancer Translational Genomics in LeukaemiaMay 2020Targeting cytokine- and therapy-induced PIM1 activation in preclinical models of T-cell acute lymphoblastic leukemia and lymphoma
IL7 and glucocorticoids coordinately drive aberrant activation of PIM1 and suggests that T-ALL and T-LBL patients could benefit from PIM inhibition
Children's Cancers Published research Leukaemia Translational ResearchApril 2020Immunogenicity of the inactivated influenza vaccine in children who have undergone allogeneic haematopoietic stem cell transplant
This study provides evidence to support annual inactivated influenza vaccine administration to children following allogeneic haematopoietic stem cell transplant
Children's Cancers Published research Academic Biostatistics Infectious Diseases Epidemiology Vaccine Trials Group Brain Tumour Research Leukaemia Translational ResearchMarch 2019Targeting the bone marrow microenvironment: a novel therapeutic strategy for pre-B acute lymphoblastic leukemia
Our findings shed light on the mechanisms of leukemia-induced bone loss
Children's Cancers Published researchJuly 2019Romidepsin enhances the efficacy of cytarabine in vivo, revealing HDAC inhibition as a therapeutic strategy for KMT2A-rearranged acute lymphoblastic leukemia
In this study, we investigate the in vivo synergy between romidepsin and cytarabine
Children's Cancers Published research Leukaemia Translational Research Translational Genomics in LeukaemiaDecember 2018A novel, palatable paediatric oral formulation of midazolam: Pharmacokinetics, tolerability, efficacy and safety
We conclude that the novel chocolate-based formulation of midazolam provides improved tolerability while remaining efficacious
Published research Leukaemia Translational Research Children's Lung HealthNovember 2018New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment
We provide evidence that targeting leukemia-induced bone loss is a therapeutic strategy for pre-B ALL
Children's Cancers Published research Leukaemia Translational ResearchJanuary 2018Taste evaluation of a novel midazolam tablet for pediatric patients: In vitro drug dissolution, in vivo animal taste aversion and clinical taste perception profiles
This study utilized in vitro, in vivo and clinical data to evaluate the palatability of a novel midazolam chocolate tablet.
Published research Leukaemia Translational ResearchJanuary 2017Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin
Identified romidepsin as a promising therapeutic for mixed lineage leukemia (MLL)-rearranged infant acute lymphoblastic leukemia
Children's Cancers Published research Academic Biostatistics Leukaemia Translational Research Computational BiologySeptember 2016High expression of connective tissue growth factor accelerates dissemination of leukaemia
Functional role of CTGF in altering disease progression in a lymphoid malignancy
Children's Cancers Published research Leukaemia Translational ResearchJanuary 2016Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin
Present a valuable resource for drug discovery and have identified ROM as a promising therapeutic for MLL-rearranged iALL
Published research Leukaemia Translational Research Computational BiologyMay 2015The role of CCN family genes in haematological malignancies
Haematological malignancies, although a broad range of specific disease types, continue to show considerable overlap in classification, and patients are...
Children's Cancers Published research Leukaemia Translational ResearchApril 2014Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis
Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell...
Children's Cancers Published research Pregnancy and Early Life Immunology Leukaemia Translational Research -
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