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Prof David Eisenstat

Prof David Eisenstat

Details

Role Group Leader / Honorary Fellow Manager
Research area Stem Cell Medicine
Prof David Eisenstat is a Paediatric Haematologist-Oncologist, Neuro-Oncologist and clinician-scientist. During David's first postdoctoral fellowship at UCSF (1991-93), he studied in the field of Molecular Neuro-Oncology at the Brain Tumor Research Center. In his second PDF at UCSF from 1993-97, he studied with Prof. J. Rubenstein who was the first to link DLX homeobox genes to brain development (Anderson S et al, Science 1997). David developed specific antibodies to the DLX transcription factors and characterized several DLX mutant mice, including the Dlx1/Dlx2 double knockout mice and other genetically engineered mouse models. In David's laboratory at the University of Manitoba (1999-2011) they assessed Dlx genes in retinal development (de Melo et al, J Comp Neurol 2003; Zhou et al, Nucleic Acids Res 2004), the retinal phenotype of the Dlx mutant mice (de Melo et al, Development 2005) and applied chromatin immunoprecipitation technologies (ChIP) to characterize DLX transcriptional targets in retinal and brain development (Le et al J Biol Chem 2007). They have identified key factors regulated by DLX1 and/or DLX2 including Brn3b (Zhang et al, Development 2017), Gad1/Gad2 (Le et al, J Neurosci 2017), and TrkB (de Melo et al, Nucleic Acids Res 2008). David's lab also identified the retinoblastoma gene family member and tumor suppressor p107 as a direct DLX target and discovered that DLX2 is expressed in retinoblastoma in both human and mouse tumors. David's lab then relocated to the University of Alberta in 2012 and subsequently to the Murdoch Children’s Research Institute, University of Melbourne in 2021. The lab identified the tumor suppressor Apc and the stem cell marker Bmi-1 as direct DLX targets in the intestine, with applications to colorectal cancers. In addition, they have studied gene expression in the zebrafish, cloned the chick Dlx1 gene and used gain and loss of function studies of Dlx1 in the developing chick by manipulating gene expression in ovo (Jiang et al BioRxiv 2020). Recent work has emphasized how DLX transcription factors regulate cell fate decisions in the developing brain and how this developmental program could be co-opted towards differentiation of diffuse intrinsic pontine gliomas (diffuse midline gliomas) and paediatric high-grade gliomas with Histone H3K27M and H3G34R/V mutations, respectively.
Prof David Eisenstat is a Paediatric Haematologist-Oncologist, Neuro-Oncologist and clinician-scientist. During David's first postdoctoral fellowship at UCSF (1991-93), he studied in the field of Molecular Neuro-Oncology at the Brain Tumor Research...
Prof David Eisenstat is a Paediatric Haematologist-Oncologist, Neuro-Oncologist and clinician-scientist. During David's first postdoctoral fellowship at UCSF (1991-93), he studied in the field of Molecular Neuro-Oncology at the Brain Tumor Research Center. In his second PDF at UCSF from 1993-97, he studied with Prof. J. Rubenstein who was the first to link DLX homeobox genes to brain development (Anderson S et al, Science 1997). David developed specific antibodies to the DLX transcription factors and characterized several DLX mutant mice, including the Dlx1/Dlx2 double knockout mice and other genetically engineered mouse models. In David's laboratory at the University of Manitoba (1999-2011) they assessed Dlx genes in retinal development (de Melo et al, J Comp Neurol 2003; Zhou et al, Nucleic Acids Res 2004), the retinal phenotype of the Dlx mutant mice (de Melo et al, Development 2005) and applied chromatin immunoprecipitation technologies (ChIP) to characterize DLX transcriptional targets in retinal and brain development (Le et al J Biol Chem 2007). They have identified key factors regulated by DLX1 and/or DLX2 including Brn3b (Zhang et al, Development 2017), Gad1/Gad2 (Le et al, J Neurosci 2017), and TrkB (de Melo et al, Nucleic Acids Res 2008). David's lab also identified the retinoblastoma gene family member and tumor suppressor p107 as a direct DLX target and discovered that DLX2 is expressed in retinoblastoma in both human and mouse tumors. David's lab then relocated to the University of Alberta in 2012 and subsequently to the Murdoch Children’s Research Institute, University of Melbourne in 2021. The lab identified the tumor suppressor Apc and the stem cell marker Bmi-1 as direct DLX targets in the intestine, with applications to colorectal cancers. In addition, they have studied gene expression in the zebrafish, cloned the chick Dlx1 gene and used gain and loss of function studies of Dlx1 in the developing chick by manipulating gene expression in ovo (Jiang et al BioRxiv 2020). Recent work has emphasized how DLX transcription factors regulate cell fate decisions in the developing brain and how this developmental program could be co-opted towards differentiation of diffuse intrinsic pontine gliomas (diffuse midline gliomas) and paediatric high-grade gliomas with Histone H3K27M and H3G34R/V mutations, respectively.

Top Publications

  • Duchatel, RJ, Jackson, ER, Parackal, SG, Kiltschewskij, D, Findlay, IJ, Mannan, A, Staudt, DE, Thomas, BC, Germon, ZP, Laternser, S, et al. PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma. Journal of Clinical Investigation 2024
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  • Ziegler, DS, Lehmann, R, Eisenstat, DD. A paradigm shift in how we treat pediatric low grade glioma - targeting the molecular drivers. Neuro-Oncology noae008 2024
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  • Toro, C, Felmingham, B, Jhadav, M, Celermajer, DS, La Gerche, A, O'Sullivan, J, Kumar, S, Mateos, MK, Fulbright, J, Govender, D, et al. Lessons learnt in the first year of an Australian pediatric cardio oncology clinic.. Cardiooncology 9(1) : 45 2023
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  • Furst, L, Roussel, E, Leung, R, George, A, Firestein, R, Faux, M, Eisenstat, D. MODL-12. REGULATION OF OLIGODENDROGLIAL PROGENITOR CELL (OPC) CELL FATE IN DIFFUSE MIDLINE GLIOMA (DMG) BY THE HOMEOBOX TRANSCRIPTION FACTOR DLX2. Neuro-Oncology 25(Supplement_5) : v300 -v301 2023
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  • Jackson, E, Duchatel, R, Staudt, D, Persson, M, Mannan, A, Yadavilli, S, Parackal, S, Game, S, Chong, WC, Jayasekara, WS, et al. EXTH-36. COMBINING ONC201 AND PAXALISIB FOR THE TREATMENT OF DIFFUSE MIDLINE GLIOMA (DMG); THE PRECLINICAL RESULTS UNDERPINNING THE INTERNATIONAL PHASE II CLINICAL TRIAL (NCT05009992). Neuro-Oncology 25(Supplement_5) : v232 -v232 2023
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