A5052849707- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Biochemical and Molecular Research
- CAR-T cell therapy research
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Sperm and Testicular Function
- Plant Molecular Biology Research
- Lymphoma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Plant Reproductive Biology
- HIV/AIDS drug development and treatment
- Chronic Lymphocytic Leukemia Research
- Advancements in Semiconductor Devices and Circuit Design
- Kruppel-like factors research
- Neuroblastoma Research and Treatments
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Autophagy in Disease and Therapy
- Photosynthetic Processes and Mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer-related molecular mechanisms research
- Genetics and Neurodevelopmental Disorders
- Silicon Carbide Semiconductor Technologies
University of Hong Kong
2012-2024
The University of Melbourne
2021-2024
Peter MacCallum Cancer Centre
2019-2024
Chinese University of Hong Kong
2020-2024
Abstract Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B lymphoma and multiple myeloma 1–4 , but efficacy CAR in solid tumours been limited 5 . This is owing to a number factors, including immunosuppressive tumour microenvironment that gives rise poorly persisting metabolically dysfunctional cells. Analysis anti-CD19 cells used clinically shown positive outcomes are associated with more...
Abstract The BCL6 Corepressor (BCOR) is a component of variant Polycomb repressive complex 1 (PRC1) that essential for normal development. Recurrent mutations in the BCOR gene have been identified acute myeloid leukaemia and myelodysplastic syndrome among other cancers; however, its function remains poorly understood. Here we examine role haematopoiesis vivo using conditional mouse model mimics observed haematological malignancies. Inactivation Bcor haematopoietic stem cells (HSCs) results...
The development of pollen wall with proper sporopollenin deposition is essential for viability and male fertility in flowering plants. Sporopollenin a complex biopolymer synthesized from fatty acid phenolic derivatives. Recent investigations Arabidopsis have identified number anther-specific genes involved the production fatty-acyl monomers potentially required exine formation. existence ancient biochemical pathways biosynthesis has been widely proposed but experimental evidence plant...
Article6 May 2022Open Access Source DataTransparent process Inhibition of pyrimidine biosynthesis targets protein translation in acute myeloid leukemia Joan So orcid.org/0000-0001-6550-0637 The Peter MacCallum Cancer Centre, Melbourne, Vic., Australia Sir Department Oncology, University Parkville, Contribution: Data curation, Investigation, Methodology, Writing - original draft, Project administration, review & editing Search for more papers by this author Alexander C Lewis...
Peripheral T-cell lymphoma (PTCL) is a rare, heterogenous malignancy with dismal outcomes at relapse. Hypomethylating agents (HMA) have an emerging role in PTCL, supported by shared mutations myelodysplasia (MDS). Response rates to azacitidine PTCL of follicular helper cell origin are promising. Guadecitabine decitabine analogue efficacy MDS. In this phase II, single-arm trial, patients received guadecitabine on days 1-5 28-day cycles. Primary end points were overall response rate (ORR) and...
Approximately 20% of acute myeloid leukemia (AML) patients carry mutations in IDH1 or IDH2 that result over-production the oncometabolite D-2-hydroxyglutarate (2-HG). Small molecule inhibitors block 2-HG synthesis can induce complete morphological remission; however, almost all eventually acquire drug resistance and relapse. Using a multi-allelic mouse model IDH1-mutant AML, we demonstrate clinical inhibitor AG-120 (ivosidenib) exerts cell-type-dependent effects on leukemic cells, promoting...
Nucleosome assembly proteins (NAPs) have been identified as histone chaperons. Testis-Specific Protein, Y-Encoded-Like (TSPYL) is a newly arisen NAP family in mammals. TSPYL2 can be transcriptionally induced by DNA damage and TGFβ causing proliferation arrest. TSPYL1, another TSPYL member, has poorly characterized the only member known to causal of lethal recessive disease humans. This study shows that TSPYL1 play an opposite role signaling. partners with transcription factor FOXA1...
Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. We have previously shown that Tspyl2 knockout mice had impaired learning and sensorimotor gating, TSPYL2 facilitates expression of Grin2a Grin2b through interaction with CREB-binding protein. To identify other genes regulated by TSPYL2, here, we showed increased level H3K27 trimethylation (H3K27me3) hippocampus, interacted methyltransferase enhancer zeste (EZH2)....
Abstract The ubiquitous metabolite heme has diverse enzymatic and signalling functions in most mammalian cells. Cells can salvage from the extracellular environment or synthesise de novo succinyl-CoA glycine through a series of 8 reactions catalysed by biosynthesis enzymes (HBEs) localised mitochondria cytosol 1,2 . Through integrated analyses mouse models, human cell lines primary patient samples, we identify as selective dependency acute myeloid leukaemia (AML). is underpinned propensity...
To determine the importance of testis-specific, Y-encoded-like 1 (TSPYL1) in survival and male factor fertility mice.Experimental prospective study.Research laboratories a university medical faculty.We generated Tspyl1 knockout (KO) mouse lines by CRISPR/Cas9. The were maintained pairing heterozygous mice to provide wild-type control KO males for comparison.None.Mendelian ratio, body testis weight, histology, sperm motility, mating tests, pregnancy outcome, transcript levels genes...
ABSTRACT Acute myeloid leukemias (AML) are comprised of multiple cell types with distinct capabilities to propagate the disease and resist therapy. Approximately 20% AML patients carry gain- of-function mutations in IDH1 or IDH2 that result over-production onco-metabolite 2-HG. Although IDH inhibitors can induce complete morphological remission, almost all eventually relapse. Analysis clinical samples suggests a population mutant cells is able persist during treatment acquiring 2-HG...
Abstract The efficacy of chimeric antigen receptor (CAR) T cell therapy is limited in solid tumors by several factors including the immunosuppressive tumor microenvironment that gives rise to poorly persisting and metabolically dysfunctional cells. To overcome this, we sought identify transcription could enhance CAR fitness. We identified overexpression Foxo1 therapeutic murine cells setting syngeneic immunocompetent models was dependent on sustained production proinflammatory cytokines....
Abstract The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) catalyzes one of the rate-limiting steps in de novo pyrimidine biosynthesis, a pathway that provides essential metabolic precursors for nucleic acids, glycoproteins and phospholipids. DHODH inhibitors (DHODHi) are clinically used autoimmune diseases emerging as novel class anti-cancer agents, especially acute myeloid leukemia (AML) where starvation was recently shown to reverse characteristic differentiation block AML...