Ursula Kees Fellow, CLCRF; Co-head, Leukaemia and Cancer Genetics
PhD
Areas of research expertise: Genetics, Molecular biology, Animal models, Preclinical studies
Dr Sébastien Malinge is a Senior Research Fellow highly qualified in the field of paediatric leukaemia, with a strong background in the mechanisms of leukaemia predisposition and development in children with Down syndrome. He obtained his PhD in 2006 from the Necker-Enfants Malades Hospital (Paris children's hospital, France) and was subsequently awarded a prestigious research fellowship by the Leukaemia and Lymphoma Society to join Northwestern University (Chicago, USA). In 2012, following his post-doctoral training, he further developed his research projects as an independent investigator at the French National Institute for Health and Medical Research (INSERM), located at the first Cancer Centre in Europe, the Gustave Roussy Institute. In 2017, Dr Malinge relocated to the Telethon Kids Institute as the Children`s Leukaemia and Cancer Research Foundation (CLCRF) fellow, to co-lead the West Australian Paediatric Leukaemia and Cancer Genetics preclinical research program within the Telethon Kids Cancer Centre.
Based on a solid background in fundamental research, next generation sequencing and the development of preclinical Patient Derived Xenograft (PDX) models, Dr Malinge is now developing cutting-edge approaches to unravel new vulnerabilities in leukaemia cells, with the view of identifying alternative therapeutic approaches and new effective treatments, to make a tangible difference to the way we treat paediatric leukaemia.
In the news:
Find Sèbastien Malinge on Google Scholar and ORCID.
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Projects
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Publications
January 2021
DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3
DYRK1A is a serine/threonine kinase encoded on human chromosome 21 (HSA21) that has been implicated in several pathologies of Down syndrome (DS), including cognitive deficits and Alzheimer's disease. Although children with DS are predisposed to developing leukemia, especially B cell acute lymphoblastic leukemia (B-ALL), the HSA21 genes that contribute to malignancies remain largely undefined. Here, we report that DYRK1A is overexpressed and required for B-ALL. Genetic and pharmacologic inhibition of DYRK1A decreased leukemic cell expansion and suppressed B-ALL development in vitro and in vivo.
Children's Cancers Published 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 Research Subsite: Cancer Translational Genomics in LeukaemiaJuly 2021Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society
Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome.
Published research Translational Genomics in Leukaemia Child disabilityNovember 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 LeukaemiaAugust 2020SNAIL trail in myeloid malignancies
Transcription factors known to induce the epithelial-to-mesenchymal transition (EMT) (such as ZEB1/2 [zinc finger E-box binding homeobox 1/2], SNAI1/2/3, and TWIST1/2) have been undoubtedly implicated in tumorigenesis, cancer progression, metastasis, and chemoresistance in solid tumors; however, their role in normal and malignant hematopoiesis has been underappreciated for many years.
Children's Cancers Published research Translational Genomics in LeukaemiaAugust 2020Gain of chromosome 21 in hematological malignancies: lessons from studying leukemia in children with Down syndrome
Structural and numerical alterations of chromosome 21 are extremely common in hematological malignancies. While the functional impact of chimeric transcripts from fused chromosome 21 genes such as TEL-AML1, AML1-ETO, or FUS-ERG have been extensively studied, the role of gain of chromosome 21 remains largely unknown.
Children's Cancers Published research Leukaemia Translational Research Translational Genomics in LeukaemiaAugust 2020Human erythroleukemia genetics and transcriptomes identify master transcription factors as functional disease drivers
Acute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes.
Children's Cancers Published research 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 LeukaemiaJuly 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 LeukaemiaNovember 2018A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis
Here we report that CHAF1B is required for normal hematopoiesis while its overexpression promotes leukemia
Children's Cancers Published research Translational Genomics in LeukaemiaJuly 2018Partial trisomy 21 contributes to T-cell malignancies induced by JAK3-activating mutations in murine models
This JAK3A572V knockin model is a relevant new tool for testing the efficacy of JAK inhibitors in JAK3-related hematopoietic malignancies
Children's Cancers Published research Translational Genomics in Leukaemia -
Education & Qualifications
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Awards/Honours